PMID- 2093774 TI - [Early diagnosis of malignant tumors of the the ovary using ultrasound]. AB - On Gynecology-Obstetric Clinic in Sarajevo in 100 women, aged 22-80, was made the indication for laparotomy because of the changes on ovaries and it was done according to the palpatory, ultrasound and laparoscopic examination. After the operative treatment and pathologic verification from the 100 studied tumors were found 15 (15%) carcinous cystadenoma, 2 (2%) mucinous cystadenocarcinoma, 25 (25%) serous cystadenoma, 10 (10%) serous cystadenocarcinoma, 10 (10%) adenocarcinoma, 23 (23%) teratoma and 13 (13%) tumors of the other kind, 25 (25%) of tumors were malign and 75 (75%) was benign. The predicted value of the ultrasoundly proved malignity was 80% (20 from 25 patients) and for the benign tumors it was 96% (72 from 75 patients). Malignant tumor of ovary is the third most common malignant disease of genital organs of a woman and at the same time the most often cause of death of women suffering from gynecologic malignant diseases. From all kinds of gynecologic malignant tumors 25% are carcinoma of ovaries. It is the cause of death in 47% women with the malignant diseases of genital organs. The bad prognosis of this tumor is mostly caused by the late diagnosis. Patients most often do not feel any disturbances until the illness comes to the phase of methastase and the most of patients (60-70%) at the time of diagnosis is already in the III or IV stage of illness. PMID- 2093775 TI - [Etiologic aspects of disorders of social adaptation in children and adolescents]. AB - Social adjustment disorders of children and youth make a significant problem of contemporary society. It provokes general interest of health services, social environment, administration of justice, public security services, in fact of society on the whole. These disorders are not born in a social vacuum, but there and now, between us. Most often they are provoked by other people examples, in which are involved other factors, that divided authors in three categories within biological, psychological and sociological theories about disorders of social adjustment in the development age of children. Each of the theories is largely analysed. At the end the authors present the important signals, which help us to detect these disorders on time, and make it possible to prevent their further development by therapeutic means. PMID- 2093776 TI - [Obstetrical approach in prenatal diagnosis in the first and second trimester of pregnancy]. AB - From 712 women-patients in Genetic Consultation Department 284 of them were submitted to antenatal diagnostics. The most common indications were old age of pregnant women or a malformed child in the previous pregnancies or in the family. Horion biopsy was done in 118 patients and amniocentesis was performed in the I and II trimester of pregnancy in 188 of them. The fetal loss according to the weeks of pregnancy in the groups, where was done the antenatal diagnostic treatment was not significantly different from horion biopsy was 1.9% and the success of cultivating of horion tissue was 98%. The findings of chromosome analysis were confirmed in all cases. PMID- 2093778 TI - [Markers in the sarcoidosis process--parameters of activity]. PMID- 2093777 TI - [Injury of the knee joint associated with popliteal artery injury--case report]. AB - In this paper we consider that it is necessary to neglect injuries of blood vessels, because often the surgeon pays all his attention to the instability of knee and in every luxation of injury of knee joint is necessary to take care of vascular status. Necessary is the operative treatment in the optimal time, in team work with the determined order in treatment. Everything done contrary to this, surely leads to the amputation of extremities. PMID- 2093779 TI - Methods and goals of speech production research. AB - A personal view of current issues in speech production research is presented with some historical comments. Particular emphasis is placed on issues directly concerned with the relation between abstract phonological representations and speech signals, using a model of speech organization in reference to articulatory movement patterns. Experimental methods to support such linguistic research efforts, including some instrumental methods for recording articulatory data, are also reviewed from this particular point of view. Preparatory sections review the physical process and some physiological studies. The discussion focuses on the temporal organization of speech, deviating from the classical segmental concatenation and coarticulation principles, and discussing new possibilities about phonetic implementation in conjunction with an abstract representation framework of nonlinear phonology. PMID- 2093780 TI - Acoustic parameters in human speaker recognition. AB - Four speaker identification tests were conducted using five female speakers known to the listeners. Starting from acoustic recordings of reiterant "ma" syllables, the perceptual importance of the following three factors was investigated: F0 height, F0 contour, and speech rhythm. For speakers with typically low or high voices F0 height turned out to be a highly relevant cue in speaker identification. For all speakers F0 contour was of secondary importance, whereas speech rhythm had a small but consistent influence on recognition rates. It could be inferred that remaining factors alone (mainly global spectral information) would yield recognition scores of approximately 50%. Consistent with previous investigations, the relevance of perceptual cues in the recognition of familiar voices was shown to be not hierarchically fixed, but to depend on speaker specific voice characteristics. PMID- 2093781 TI - [Value of C-reactive protein in the evaluation of activity in ulcerative colitis and Crohn's disease]. AB - We studied a value of measuring the C-reactive protein (CRP) serum concentration in the assessment of ulcerative colitis and Crohn's disease activity. From a large register of patients with the inflammatory bowel disease (IBD), we have chosen randomly 91 patients: 61 with ulcerative colitis and 30 with Crohn's disease. As a reference point in the assessment of ulcerative colitis we have used the Powell-Tuck clinical index. Nineteen patients had an active disease, and 42 were in a remission. Patients with the active disease had significantly higher levels of the CRP then the patients in remission (chi 2 = 4.99; alpha less than 0.05). Serum CRP levels and the disease activity assessment by Powell-Tuck index were in a positive correlation, according to the Fisher's exact test (p less than 10(-8)). In the group of 30 patients with Crohn's disease, the disease activity was assessed by CDAI ("The Crohn's Disease Activity Index") and by van Hees index. According to CDAI, 26 patients were in a remission, and only 4 had an active disease. According to van Hees index, there was no patient in a complete remission, 17 patients had a partial remission and 13 had an active disease. Patients with the active disease had significantly higher CRP levels then the patients in remission, according to van Hees index (chi 2 = 7.863; alpha less than 0.01), but not according to CDAI (not significant). Meanwhile, the Fisher's exact test suggested a high positive correlation between the disease activity assessment with both indexes, either CDAI or van Hees, and the CRP serum values (alpha less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2093782 TI - [Osmotic resistance in erythrocytes in patients with chronic kidney insufficiency]. AB - Anemia almost always found in patients with end-stage chronic renal failure has long been known to be related to secondary hyperparathyroidism. Parathormone leads to anemia in different ways, one being the lowered osmotic resistance. In the present paper we report on the osmotic resistance of erythrocytes in 57 patients with a progressive stage of chronic renal failure treated at the Hemodialysis Centre of the Osijek General Hospital. The aim of our study was to establish the relationship between the osmotic resistance and parathormonal level. The average value of the osmotic resistance median (ORM) in erythrocytes of patients with chronic renal failure (0.37 +/- 0.03) was lower than in healthy probands (0.39 +/- 0.02). The difference was statistically significant (t = 2.93, p less than 0.01). No correlation between C-terminal parathormone and the average values of erythrocytic ORM in the whole group or in the subgroup of 7 patients with pathologic values of erythrocytic ORM was found. In patients treated with calcium antagonists, the average value of erythrocytic ORM was not significantly lower than in patients not on these drugs. Allowing the assumption that active parathormone has a high share in C-terminal parathormone, we conclude that the lowered osmotic resistance of erythrocytes is not necessarily found in patients with chronic renal failure. PMID- 2093783 TI - [Analysis of the frequency, types and justification for radiographic examination based on a sample of a community population]. AB - According to the patient's general practitioner files of the Health centre "Josip Adamic" Ivanic-Grad, all x-ray diagnostic examinations carried out in health insured persons of the Ivanic-Grad community were analyzed between 1983 and 1987. During the period, a total of 22,615 x-ray examinations were done. An average number of 0.761 radiographs was performed and the average x-ray dose to which patients were exposed was 126.62 mrads (1.26 mGy). The site of most usual examination was the thorax (44.1%). Males underwent more x-ray examinations than females (53.2% versus 46.8%). X-rays of thorax, head and neck, arms and legs were more frequent in males, while abdomen and pelvis x-ray examinations and diascopies were more usual in females. The greatest number of x-ray examinations was performed between the ages of 0 to 20 years of age, and patients were exposed to the highest x-ray dose between the ages of 41 to 60 years of age. The average gonadal dose was 58.78 mrads (0.58 mGy) per year. Clinical examinations preceded radiologic examinations in 81.3% of cases, laboratory investigations in 9.7% and other non-radiologic examinations in 1.4% of cases. The working diagnosis existed before x-ray examination in 77% of cases and pathological findings were discovered in 32.7% of cases. PMID- 2093784 TI - [AIDS--motivation of people for testing (analysis of a questionnaire)]. AB - At the Department for Transfusiology of the Osijek General Hospital, the blood of volontary donors has been tested for anti-HIV since July 1, 1987, according to regulations. In the period from July 1, 1987, to June 30, 1989, 49 persons come to be tested for anti-HIV on their own initiative. This test group was asked to fill in a questionnaire. The same questionnaire was given to the control group of 154 volontary blood donors. The data were evaluated statistically using the chi 2 test. Statistically significant differences between the two groups (p less than 0.05) have been found in the following parametres: - sex (more men in the control group, but it must be noted that in the observed period there were 82.63% of men among volontary blood donors); - knowledge about obligatory anti-HIV testing of the blood of volontary donors since July 1, 1987 (the test group was not well informed);--motivation for testing (the test and control groups differed in 5 of 8 suggested motives. The leading motives in the test group were sexual contact with an unknown partner, temporary job in the USSR, sexual contact with a partner likely to be seropositive or diseased and the pressure of the social environment to undergo the test for anti-HIV. The strongest motive in the control group was curiosity, which is interesting since public health institutions propose resistance from blood donation of the high risk group members as a post of safe transfusion);--knowledge of preventive measures (the test group was better informed). PMID- 2093785 TI - [Epidemiologic characteristics of acute and recurrent middle ear inflammation in childhood]. AB - The authors studied the incidence of acute and relapsing inflammations of the middle ear, together with factors relating to inflammation in 393 children aged up to 36 months. The results revealed that of 393 children followed up for 12 months, 175 (44.52%) had acute otitis media and 40 (22.85%) had relapses. No relationship was found between age and acute inflammation, but the rate of relapses was significantly higher during the first year of life. There was no significant influence of the sex of the child, socioeconomic status and place of living on the appearance of the inflammations. The attendance of infant nurseries and day-care centres had significant influence on higher rate of acute inflammations but not on relapses. There was no influence of acute otitis media of the members of the family on incidence of the same disease in their children, but there was evidence of influence on relapses. The highest incidence of inflammation occurred in autumn and winter months, November, December and January (61.67%) versus only 1.76% in summer months (July, August). Only 2 children had scars of the eardrums presenting as an early consequence of the disease, while none had any complications of the middle ear inflammation. PMID- 2093786 TI - [Myasthenia gravis in pregnancy]. AB - Twenty-nine patients with myasthenia gravis in pregnancy have been presented. These patients represent a total of 31 deliveries and 33 newborns. Despite that myasthenia gravis is an illness that poses potentially grave complications for both mother and infant, there were no maternal and neonatal deaths. Only two patients experienced significant exacerbation of their disease during pregnancy. Most of patients underwent vaginal delivery. Cesarean section is not indicated unless there are obstetrical reasons. Incidence of cesarean section delivery was 16.1%. Vacuum extractor has been used to shorten the second stage of labor and its incidence was 16.1%. In the seven (22.6%) patients myasthenic signs and symptoms got worse during the postpartal period. Neonatal myasthenia gravis was observed in 13 (39.4%) newborns. Inverse relationship was found between neonatal myasthenia and duration of disease in mothers. Incidence of neonatal myasthenia was higher in newborns born by mothers with short duration of myasthenia gravis. PMID- 2093788 TI - [Peripheral uveitis caused by Toxocara larvae]. AB - The authors present an eight year old girl suffering from peripheral uveitis caused by Toxocara sp. larva migration. Chronic uveitis was already present when the girl went to the Ophthalmology Outpatient Clinic because of lack of sight in her right eye. Carefully taken past medical history, especially epidemiological, as well as history of recent complaints (fever, general infectious syndrome), pointed to the possible toxocariasis. A specialist for infectious diseases was consulted, tests made and diagnosis has been established by positive enzyme linked immunosorbent assay test (ELISA)--the absorption value being E405 = 0.76 to Toxocara canis. The findings of a CT scan and ultrasonography of the eye were consistent with toxocariasis. Thiabendazole therapy administered at this stage of the disease has not shown to be effective. PMID- 2093787 TI - [Epidemiology of enteroviral meningitis in Croatia 1958-1988 with special emphasis on the great epidemic of 1988]. AB - In 1988, there was a large outbreak of enteroviral meningitis in the Republic of Croatia and in other parts of Yugoslavia as well. A total of 4079 cases of enteroviral meningitis were registered with one fatal outcome (Mb 8.7 0/ooo). The outbreak was caused by echovirus 4. Analysis of epidemiological, virologic and ecological data for 1988, as well as for a number of previous years, showed the following: an upward morbidity trend observed from 1958 to 1979 turned to a high level stationary trend with irregular annual oscillations. A cyclic morbidity trend was noticed with peaks in 9-10 years. Seasonal peak was lower in July regularly. In 1988, age and sex distribution of the diseased persons differed from the usual picture, showing greater proportion of older age and women. The probable reason is in the long absence of echovirus 4 from the target population, resulting in low herd immunity. This caused greater proportion of older cases, among which women (mothers) had probably been more exposed to infections than men (nursing ill household members, laundry handling, etc). The epidemic years 1988 and 1979 were hot during spring and summer, at above-average level. Such climatic factors (high temperature) coupled with the sufficiently low level of herd immunity probably triggered in both examples the outbreak of enteroviral meningitis. PMID- 2093789 TI - [Diagnostic characteristics of myxoma of the left atrium]. AB - Three middle-aged patients (38, 40 and 41 years old; two women and one man) with left atrial myxoma diagnosed by echocardiography and successfully operated on are presented. Two patients had tumor embolus as the dominant presenting symptom. The time span between the first symptoms and the echocardiographic diagnosis was 6 months, 12 months, and 12 days, respectively. From that moment to surgery the average lag was 6.3 days only, including the complex transportation to distant surgical centres. All the patients are now alive, all with normal findings more than 2 years after the operation. PMID- 2093790 TI - [Ceftazidime in the therapy of gram-negative meningitis in childhood]. AB - Six cases of neonatal meningitis due to E. coli (3 cases), K. pneumoniae (1 case), P. aeruginosa (1 case) and S. marcescens (1 case), and eleven cases of suckling and little child meningitis caused by M. influenzae (10 cases) and N. meningitidis (1 case) were treated with ceftazidime. The susceptibility of agents was qualitatively tested according to the disk-diffusion method, and quantitatively according to biological dilution method on liquid broth. Ceftazidime concentrations in cerebrospinal fluid and sera were determined by the modified microbiological method using diffusion on agar. Efficacy of ceftazidime therapy was assessed by quickness of cerebrospinal fluid "sterilization", duration of antimicrobial therapy and outcome of the disease. In spite of very good agents susceptibility to ceftazidime determined by disk-diffusion method, notable differences were found in quantitatively determined susceptibility (minimal inhibitory and minimal bactericidal concentration). Antibiotic penetrability was various in proportion with individual intensity of blood brain barrier break down. Bactericidal effect and prompt "sterilization" of cerebrospinal fluid within 48 hours after the beginning of ceftazidime therapy was achieved in those patients in whom ceftazidime cerebrospinal fluid concentration was 10 and several times higher than the minimal bactericidal concentration (all cases due to H. influenzae, N. meningitidis and E. coli). In these cases the issue of the disease was also favourable and none of the patients died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2093791 TI - [Development of problems in medicine]. AB - Current problems of medical profession stem from several independent points. The development of biomedical sciences generates a numerous basic and applied discoveries, what opens a new insight into pathobiology of diseases. Biomedical faculties have been introducing molecular biology research programmes, in order to keep up with the contemporary demands of their scientific university position. Teaching university hospitals are specific in their performance, comprising simultaneously three activities: scientific research, teaching of biomedical courses and regular clinical work. All three activities are as equally important in achieving the status of teaching university hospital. Author stresses that some of the university hospitals have failed to make a proper functional organization between the emergency medicine and other hospital activities. Therefore, due to that they fail to meet the scientific standards and excellence of performance of the university teaching hospitals. Concerning the imminent programme of the six year study of medicine, author outlines the importance of the integrated, problem oriented teaching, which, he thinks, is more efficient in comparison to the traditional teaching of medicine. A short synopsis of basic discoveries in the various biomedical fields, as well as applied research relevant to the medical praxis are discussed at the end. PMID- 2093792 TI - [The structure and mechanism of action of insulin receptors]. AB - The insulin receptor is an integral part of plasma membrane of most cells. It consists of 2 alpha and two beta subunits. The alpha subunit is the hormone binding component, while beta subunits are a tyrosine specific protein kinase which itself can be autophosphorylated. Receptor tyrosine kinase activation upon insulin binding catalyses the phosphorylation of exogenous substrates and endogenous cellular proteins. It is reasonable to think that the insulin induced autophosphorylation, activation of its receptor kinase and changes in intracellular substrates represent important events in the action of insulin on cell metabolism and growth. PMID- 2093793 TI - [Hematopoietic growth factors]. AB - Hematopoietic growth factors are glycoproteins that stimulate the proliferation and differentiation of hematopoietic progenitor cells. Due to several technical advances, first of all to the techniques of recombinant DNA, it has become possible today to produce them highly-purified and in amounts big enough to enable its application in clinical trials. Until now, 5 hematopoietic growth factors have been studied on humans. In early clinical trials their safety and favourable biological efficacy has been proved. Obvious effectivity in vivo significantly broadens frontiers of possible therapeutic effects in several clinical conditions that include primary or secondary insufficiency of hematopoiesis. Their future applications have to include combinations of several different hematopoietic growth factors or their combinations with cytostatic drugs or immunomodulators. PMID- 2093795 TI - [Insemination or fertilization?]. PMID- 2093794 TI - [The role of professional personnel in the length of hospitalization of psychiatric patients]. AB - In this paper the qualified personnel turnover within the 25 years is presented. The following data are used: statistical data of the Psychiatric Hospital Vrapce, Zagreb, the data of Psychotic Register of the Socialistic Republic of Croatia and specially taken poll in greater psychiatric hospitals in Croatia. In order to follow the situation in psychiatric organizing scheme, particular indicators are used. In the treatment evaluation, the personnel is measured according to the number of discharged or treated patients. The changes within period of a quarter of a century in psychiatry relating to the role, number and kind of staff who participate in psychiatric patients treatment, can be summarized as significant (high) rise of the psychiatrists, certain oscillations in the number of professional associates (psychologists, social workers, special teachers and other therapists) with the tendency to increase (although still insufficient), the growth of a number of nurses slight oscillations of the number of beds with minor diminishing during the last years, inpatients number increase, changes of diagnostic structure of inpatients and significant shortening of the hospitalization period of all the psychiatric patients. The increase of the number of psychiatrists is the most important in prognosis of the inpatients treatment directly referring to the shortening of the hospitalization period and the increase of the number of discharged patients (which is generally 80-100 discharged patients annually per psychiatrist). PMID- 2093796 TI - Imaging the febrile patient. PMID- 2093798 TI - Quality assurance in general practice. PMID- 2093797 TI - Coronary angioplasty in unstable angina: time for controlled clinical trials. PMID- 2093799 TI - Renal dialysis. PMID- 2093800 TI - Short-term and long-term benefits of coronary angioplasty in unstable angina pectoris. AB - Primary coronary angioplasty was attempted in 288 patients (206 men and 82 women) who presented with stable (50%) or unstable (50%) angina pectoris. The success rates of angioplasty and the subsequent revascularization requirements in these two angina categories were compared during a one year prospective follow-up. The site and distribution of coronary artery stenoses did not differ between the categories. Three hundred and five dilatations were attempted (149 in 144 patients with unstable angina and 156 in 144 patients with stable angina). Of these procedures, 265 (87%) were technically successful--133 (89%) in 128 patients with unstable angina and 132 (85%) in 120 patients with stable angina. Lower success rates were achieved in 29 attempted dilatations of vessels with chronic total occlusion (19 successful [66%], P = 0.002) and in 19 patients who presented with unstable angina after recent (within two weeks) infarction (10 patients with successful angioplasty, [53%], P less than 0.0001). Subsequent revascularization requirements after an initially successful angioplasty in 57 patients were greater in unstable (36 patients) than in stable angina (21 patients; P = 0.05) and reflected the greater frequency of repeat angioplasty in patients with unstable angina (22 patients) compared with those with stable angina (10 patients; P = 0.04) among patients with recurrent symptoms. At one year, 245 patients (85%)-121 treated for unstable angina and 124 treated for stable angina--experienced no angina during normal daily activities. We conclude that a primary angioplasty success rate of 89% can be achieved in patients with unstable angina pectoris but this rate is significantly lower in patients presenting after recent infarction. Repeat angioplasty for recurrent symptoms after a successful primary procedure is required more frequently in patients presenting with unstable angina. PMID- 2093801 TI - Evaluation of the accuracy of the home ovulation detection kit, Clearplan, at predicting ovulation. AB - A home ovulation testing kit, Clearplan, that detects the urinary luteinizing hormone (LH) surge was compared with basal body temperature (BBT) charts and cervical scoring as a method of ovulation prediction in 54 consecutive patients. The accuracy of all these methods was evaluated using daily serum LH measurements. Clearplan was shown to be significantly more accurate at timing ovulation than were BBT charts (P less than 0.0001) and cervical scoring (P less than 0.025). In 82%-88% of cases the kit predicted ovulation within one day and in 89%-96% of cases within two days of the serum LH surge. The kits were found to be easy to use and their potential place in clinical practice is discussed; home ovulation testing may ultimately replace serum LH assays as the method of choice in timing ovulation. PMID- 2093802 TI - Interpractice visits by general practitioners: implications of a pilot project for quality assurance in general practice. AB - This article describes a pilot study involving 25 general practitioners who agreed to undertake interpractice visits. Decisions regarding the nature, length and documentation of the interpractice visit were made by consensus during a 5-h workshop. Participants met again as a group after the visits were completed and discussed the acceptability of the visits and their potential to improve standards of care. Reactions included a high level of enthusiasm to develop further the rigour of these visits. PMID- 2093803 TI - An evaluation of the Breath-Taker peak flow meter. AB - This study was designed to evaluate the Breath-Taker peak flow meter, recently released by the Asthma Foundation of Victoria. The performance characteristics of five Breath-Taker units were compared with those of five Wright and five mini Wright peak flow meters. The between-unit reproducibility of each type of peak flow meter was measured using an explosive decompression device with a peak flow reproducibility of better than 1%. Each individual meter was used to measure the peak flow delivered by the decompression device three times for each of six flow rates (97-622 L/min). The coefficient of variation (CV) was lowest for the Wright meters (mean CV, 4.8%) and, similarly to the Breath-Taker units (mean CV, 8.4%), this decreased with increasing flow. The CV of the mini-Wright meters, however, increased as flow increased (mean CV, 7.5%). The Breath-Taker meter had less inter-unit variability than the mini-Wright meter at peak flows above 200 L/min. The accuracy of the three meter types was assessed by comparing measurements of peak expiratory flow rate (PEFR) made with each type and also with a computerized pneumotachograph system in 30 subjects with various degrees of irreversible airflow obstruction. Each subject performed at least three reproducible PEFR manoeuvres on the pneumotachograph and on each type of meter, in randomized order. The results showed that in comparison with the pneumotachograph system the Breath-Taker meter underestimated PEFRs by a mean of 27 L/min and the mini-Wright meter overestimated PEFRs by a mean of 45 L/min, whereas the Wright meter was not significantly different. Since the differences between the Breath-Taker meter and the pneumotachograph were independent of flow rate, a scale offset would suffice to "correct" the Breath-Taker readings. PMID- 2093804 TI - Heroin users seeking methadone treatment. AB - Seven hundred and sixty-seven patients applying to enter public methadone programmes in the western suburbs of Sydney underwent assessment in the Drug and Alcohol Unit at Westmead Hospital between 1986 and 1988. These patients had long histories of illicit drug use and most were involved in crime, prostitution and a drug subculture. Many abused multiple drugs, and almost all had been exposed to hepatitis B virus. However, human immunodeficiency virus (HIV) seropositivity rate was low. Methadone programmes, at least in Sydney's western suburbs, attract a very disadvantaged population for whom rehabilitation is likely to be a difficult, long-term process. PMID- 2093805 TI - Psychiatry towards 2000. PMID- 2093806 TI - For this relief much thanks....? PMID- 2093807 TI - Dialysis--1989. PMID- 2093808 TI - Orthostatic tremor: a cause of postural instability in the elderly. AB - Three cases of a rarely described syndrome of posture-induced tremor of the legs and trunk, which occurs with standing but resolves with walking, sitting and lying, are described. This syndrome occurs in elderly patients and, in the three patients described, responded dramatically to a small dosage of clonazepam. PMID- 2093809 TI - Prevention of "needle-stick" injuries in hospitals. PMID- 2093811 TI - Drug-induced oesophageal ulceration. PMID- 2093810 TI - HIV-associated oesophageal ulcers treated with thalidomide. PMID- 2093812 TI - Hookworm anaemia in an aboriginal community. PMID- 2093813 TI - Rationalism versus irrationalism. PMID- 2093814 TI - Chlamydia trachomatis and SIDS. PMID- 2093815 TI - Sudden infant death syndrome (SIDS) and environmental temperature. PMID- 2093816 TI - Antibody to human T-cell lymphotropic virus type I was not detected in clients attending an aboriginal health service in Melbourne. PMID- 2093817 TI - Pregnant women and HIV. PMID- 2093818 TI - "White coat" hypertension. PMID- 2093819 TI - Nature and nurture. PMID- 2093820 TI - Perineal pain after childbirth. PMID- 2093821 TI - Metoclopramide side effects in children. PMID- 2093823 TI - What every doctor should know about economics. PMID- 2093822 TI - Recovery after childbirth. PMID- 2093824 TI - Freckles, moles, melanoma and the ozone layer. PMID- 2093825 TI - The Disability Services and Guardianship Act 1987. PMID- 2093826 TI - Chloramphenicol and bacterial meningitis. PMID- 2093827 TI - Thin-membrane nephropathy. PMID- 2093828 TI - Scuba divers at risk of decompression sickness. PMID- 2093829 TI - The misuse of mammography. PMID- 2093830 TI - A Candida-specific antibody in patients with vaginitis. PMID- 2093831 TI - Can cancer be cured by meditation and "natural therapy"? PMID- 2093832 TI - Clinical details and radiological examinations. PMID- 2093834 TI - A swallowed thermometer--what to do? PMID- 2093833 TI - Bowel-associated dermatosis-arthritis syndrome. PMID- 2093836 TI - Pneumococcal C and type polysaccharide detection in the concentrated urine of patients with bacteremia. AB - The C polysaccharide of Streptococcus pneumoniae was detected in the concentrated urine of 23 of 33 patients with pneumococcal bacteremia using latex agglutination. Type-specific polysaccharides were detected in the urine of 17 of these 33 patients including 4 patients lacking C polysaccharide in their urine. These 4 with the 23 detected above gave a total sensitivity of 82% (27/33). The concentrated urine from an additional 11 patients with other bacteremias were tested by C polysaccharide and type-specific reagents and were negative. C polysaccharide detection in the concentrated urine of patients may be helpful in the diagnosis of pneumococcal infections. PMID- 2093837 TI - A case of Candida parapsilosis endocarditis. AB - The authors report a case of Candida parapsilosis endocarditis in a non-drug addicted young patient who, 6 months before the manifestation of endocarditis, was submitted to cardiac surgery. This is the first report from Greece and the second found in the accessible literature. PMID- 2093835 TI - Interaction of lactoferrin with Escherichia coli cells and correlation with antibacterial activity. AB - It has been established that the antimicrobial activity of lactoferrin towards Escherichia coli is enhanced by a direct contact between the protein and the microbial cell and that, in the case of E. coli K-12 strains, an antibacterial activity of lactoferrin unrelated to iron withdrawal is present. Evidence is now reported that lactoferrin binds to surface structures expressed in E. coli K-12 strains grown in either an "excess" or "stress" of iron. Under the experimental conditions used, lactoferrin binding both in the apo and in the iron-saturated form yields a maximum of 1.6 X 10(5) bound molecules/E. coli K-12 cell; the amount of lactoferrin bound does not depend on the expression of the iron regulated outer membrane proteins. In contrast, lactoferrin does not bind to E. coli clinical isolates. Apo-lactoferrin (at 500 micrograms/ml in a chemically defined medium) inhibits the growth of E. coli K-12 strains but not of clinical isolates. These findings suggest that the antibacterial activity of the protein could be associated to its binding to the cell surface. PMID- 2093838 TI - Oral carriage of yeasts in two villages in Papua New Guinea. AB - Oral swabs were taken from 194 subjects in two villages in Papua New Guinea. Yeasts were isolated from 103 (53.1%) individuals of which 41 (21.1%) were Candida albicans. A wide variety of other yeasts were also identified. PMID- 2093839 TI - Fluconazole in the treatment of oropharyngeal candidosis in HIV-positive patients. AB - 106 HIV-positive patients with 129 episodes of oropharyngeal Candida infection were treated with fluconazole (50-300 mg/d). Treatment lasted from 4 to 23 days. The majority of patients were in more advanced stages of HIV infection (82% AIDS cases). Therapy with fluconazole led to complete healing or improvement of clinical symptoms in 93% of all treatment courses. However, according to cultural findings, an elimination or recession of pathogens was achieved in only 70% of cases. Cultural monitoring showed a slow reduction of pathogens, as opposed to a fairly rapid clinical improvement. Candida albicans was the most frequently isolated Candida species (n = 128); the most selected Candida species during treatment were C. glabrata, C. krusei, and C. inconspicua. It is remarkable that C. glabrata, a low-grade pathogen, caused enanthema in 2 patients and a typical oral thrush in 1 patient. Fluconazole was well-tolerated, and apart from mild gastro-intestinal symptoms in 1 patient, no severe side effects were observed. PMID- 2093840 TI - Fluconazole monitoring in Candida peritonitis based on histological control. AB - Between May 1, 1988 and January 1, 1990, 10 patients were treated for Candida peritonitis. Origins of the infections were lesions and perforations of the gastrointestinal tract. Risk factors promoting the disease were tumours, diabetes mellitus and extensive antibiotic therapy. The mean classification by the APACHE score 2 was 19.0. All patients underwent the programmed peritoneal lavage for diffuse peritonitis. Daily relaparotomy and lavage of all quadrants of the abdomen was performed. The diagnosis of Candida peritonitis had been established by microbiological investigation, increasing serologic titres, histologic demonstration of a deep mycosis and clinical picture. All patients were treated with 300 mg fluconazole daily. Five of the ten patients died from their severe primary diseases in spite of control of fungal peritonitis. Daily relaparotomies allowed to follow up the microbiologic and histologic course of the disease. Within 2 to 4 days after administration of fluconazole, hydrous swelling and reduction of fungal elements could be demonstrated histologically. On the 4th day after onset of antifungal therapy, fungal mycelia were markedly reduced and distendedly decayed. Fluconazole clearly leads to a destruction of deeply invading Candida elements within 4 days. PMID- 2093841 TI - A rapid susceptibility testing method for yeasts to 5-fluorocytosine. AB - A rapid method of susceptibility testing of yeasts to 5-fluorocytosine is demonstrated. The method is based on photometric determination of the optical density of yeast suspensions before and after incubation for 4 h in the presence of the antifungal. The method was evaluated with 50 Candida strains. PMID- 2093842 TI - Isolation of Cryptococcus neoformans var. neoformans from canine otitis. AB - Cryptococcus neoformans was demonstrated in the clinical material of a 15-year old male dog with a history of chronic otitis externa by employing Helianthus annuus seed agar as a selective medium. The examination of the isolate for sexual compatibility on modified Helianthus annuus seed medium revealed that it belonged to Filobasidiella neoformans var. neoformans 'alpha' mating type. In the authors' view, this appears to be the first report of isolation of Cr. neoformans var. neoformans from diseased ear of a dog. PMID- 2093843 TI - Experimental phaeohyphomycosis. AB - The authors performed an experimental infection of the rabbit eye with Wangiella dermatitidis which had been isolated from the corneal ulcer of a patient. The fungus was inoculated into the front chamber and the vitreous body. The disease showed a trend to spontaneous recovery. The individual phases of the experimental infection were followed by histology and electronmicroscopy, both TEM and SEM. Different stages of development of the polymorphous fungus, as sclerotic bodies, mycelial filaments and yeast-like cells, could be demonstrated. PMID- 2093844 TI - Keratomycosis caused by Dichotomophthoropsis nymphaearum. AB - A case of Dichotomophthoropsis nymphaearum, a dematiaceous hyphomycete, is described from Bangladesh. This species has not previously been reported as a human pathogen. Hyphae were observed in Gram stained corneal scrapings and the species was grown from cultured corneal material. Treatment with topical econazole and subconjunctival injections of miconazole was successful in the short term but long-term outcome could not be determined. The results of sensitivity tests for six antifungal drugs are reported for the isolate. PMID- 2093845 TI - Enzyme immunoassay detection of antibodies in canine blastomycosis using Blastomyces dermatitidis lysate antigens. AB - A Blastomyces dermatitidis yeast phase lysate antigen (T-58) prepared in our laboratory was used in an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies in 201 serum specimens from dogs with blastomycosis. In addition 36 sera from non-infected dogs from an endemic area for blastomycosis and 36 sera from non-infected dogs residing in a blastomycosis non-endemic area were assayed. Sensitivity values ranged from 96.2% (53 pre-treatment sera) to 88.5% (148 post-treatment sera) with the specimens from dogs with confirmed blastomycosis. Minimal reactivity was experienced with the sera from non-infected dogs. Positive reactions were obtained with 8.3% of the endemic area sera and with 5.6% of the sera from the non-endemic area. Mean ELISA index values ranged from 7.66 with the pretreatment sera to 1.11 and 1.03 with the endemic area sera and non-endemic area specimens respectively. PMID- 2093846 TI - White piedra: ultrastructure and a new microecological aspect. AB - White piedra or trichosporosis is a superficial mycosis of the hair shaft, caused by the yeast Trichosporon beigelii; it has been found in all continents and may involve the hair of any part of the body. We report a case of white piedra on the hairs of the inguinal fold with ultrastructural studies. Transmission electron microscopy showed that the nodules have the same morphological aspects as the fungus in culture (hyphae and arthrospores) except for the presence of a cementant substance. By scanning electron microscopy the elimination of spores was seen on the nodule surface. Interestingly similar nodules were found on cotton fibres of the patient's underwear, which were also studied by scanning electron microscopy. This finding can explain therapeutic failure and demands special hygienic conditions related to clothes. PMID- 2093847 TI - Infections caused by Trichophyton raubitschekii: clinical and epidemiological features. AB - Thirty-eight cases of human infection with the recently described dermatophyte species Trichophyton raubitschekii were studied and a description is presented of the clinical and epidemiological features of infection with this organism. Results revealed the usual preponderance of males (2:1) but a high proportion of individuals of Asian origin (60.5%) in the infected population. Tinea corporis, tinea cruris and tinea pedis were the most common infections. T. raubitschekii differed significantly from the more common Trichophyton rubrum and T. mentagrophytes in being more strongly associated with tinea corporis. Some T. raubitschekii infections produced inflammatory lesions while others clinically resembled those caused by the related species T. rubrum and T. mentagrophytes. T. raubitschekii could be distinguished from related species by means of special mycological procedures in the laboratory. PMID- 2093848 TI - Doppler hemodynamic characteristics of four widely used aortic valve prostheses. AB - Fifty-one patients with normofunctioning aortic prosthetic heart valves were evaluated by Doppler-Echocardiography to determine type-related flow characteristics. The four mechanical valves tested were: Starr-Edwards (1200-1260 aortic), Bjork-Shiley (60 degrees-60 degrees cc aortic), Medtronic-Hall (aortic) and St. Jude Medical (aortic). The most significant dynamic indexes were calculated: Peak (PG) and Mean (MG) Gradient across the valve, Cardiac Index (CI) or Cardiac Output (CO), Regurgitant Jets, Effective Orifice Area (EOA), Spectral Diagram Systolic Trend (SDST) and PVRT (time required to reach peak velocity during systole)/LVET (left ventricular ejection time) Ratio. Patients with Doppler assessed prosthetic dysfunction were dropped out of the study group. As expected, significant reverse correlation (-0.70) was found when transvalvular pressure gradients were compared with valve size. Significant direct correlation (0.82) was found when EOA was compared with valve size, thus suggesting the high reliability of the continuity equation in the assessment of the real orifice area. The Starr-Edwards valve, when compared with the other prostheses of the same size, showed the highest calculated transvalvular gradient; the St. Jude Medical showed the lowest. On the other hand, the Starr-Edwards valve was not commonly associated with regurgitation, while the St. Jude valve was usually moderately incompetent. Those hemodynamic differences should guide the selection of the ideal prosthetic valve for elective surgical indications. Doppler measurements provided noninvasive information similar to that given by cardiac catheterisation, which was reproducible and specific for valve function. According to this high sensitivity and specificity and to the absolute innocuity of the procedure, Doppler-Echocardiography should be considered the elective technique for long-term follow-up in patients with aortic prosthetic heart valves. PMID- 2093849 TI - [Effect of changes of the left ventricular diastolic pressure on the coronary circulation hemodynamics]. AB - In order to understand the effect of LVEDP changes caused by contrast injection during angiography on coronary hemodynamics we studied 15 patients (5 congestive CMP, 5 mixed angina and 5 controls). Our results do not cope with an important negative role played from LVEDP changes on coronary hemodynamics and cardiac metabolism. Actually LVEDP increase after ventriculography was balanced by coronary flow increase and impedance reduction even when the latter has been matched with LVEDP. We also observed lactate metabolism changes which are not likely to be provoked by myocardial ischemia, since there was not a definite negativization of % lactate extraction and delta A-VO2 always turned to reduction; this is apparently not in agreement with other Authors who had reported metabolic alterations suggestive for myocardial ischemia, even if they did not calculate delta A-VO2 and coronary flow. This difference could be related to the different populations studied, specially when considering the different functional meaning of coronary stenoses of the same degree at angiography. Is thus the Authors' thought that, when coronary reserve is still adequate, is it possible not to take into account LVEDP, which becomes important in patients with a more advanced coronary disease as in those cases this extravascular impedance factor to coronary flow could take his own worsening role. PMID- 2093850 TI - [Incidence of the most frequent complications in hypertensive patients]. AB - The incidence of district (cardiac, cerebral, renal) and systemic vascular complications was studied in a population of 3992 hypertensive in-patients during the period from 1984 to 1988. The total number of male hypertensive patients was always higher (2355) than that of female hypertensive patients (1637). From the analysis of results it appears that 11.01% of male hypertensive patients and 15.85% of female hypertensive patients were diagnosed as being affected by uncomplicated essential arterial hypertension, whereas 88.97% of male and 84.12% of female hypertensive patients suffered from arterial hypertension with varying percentages of cardiac, cerebral, renal or systemic-type atheroarteriosclerotic complications. The prevalence of the male sex was particularly evident in the case of cardiac complications. Given the peak incidence of the various types of complications when analysed by decade of age, an earlier incidence of cardiac and renal complications was found in male hypertensive patients which anticipates the complications found in female hypertensive patients by approximately one decade. Lastly, the paper underlines the social importance of essential arterial hypertension and the need to develop efficacious primary and secondary prevention in order to reduce the incidence of complications which today represent the most severe aspect of hypertension. PMID- 2093851 TI - [The role of therapy with a Ca++ antagonists (nifedipine) in the long-term prognosis of hypertensive patients with previous myocardial infarction]. AB - One hundred and twenty-two patients suffering from slight or moderate essential arterial hypertension with a previous history of myocardial infarction were selected for inclusion in this study. Patients were divided into two groups of 61 according to the type of anti-hypertensive therapy received. Patients in group 1 received nifedipine (30 mg p.d.), while patients in group 2 were treated using other anti-hypertensive therapy (diuretics, alpha-methyldopa, clonidine, indapamide). At the end of the follow-up period, which lasted 5 years, a statistically significant improvement in the following factors was observed in group 1 in comparison to the control group: (a) an improved response of both SBP (p less than 0.001) and DBP (p less than 0.001) levels to anti-hypertensive therapy; (b) a more significant diminution in the thickness of the interventricular septum (p less than 0.001) and the posterior wall of the left ventricle (p less than 0.001) assessed using ultrasonography; (c) a reduced number of cases of post-infarction angina (p less than 0.05); (d) fewer cases of recurrent infarction (p less than 0.05); (e) fewer deaths as a result of re infarction (p less than 0.01). These results confirm that the vascular and cardioprotective effects of nifedipine give a good long-term outcome in hypertensive patients with a previous history of myocardial infarction. PMID- 2093852 TI - [A case of rupture of the tendinous cord caused by infective endocarditis]. AB - The paper reports a case of infective endocarditis of the valve, with an insidious and slow onset accompanied by low fever, debility, loss of weight, anemia, and the concomitant echocardiographic observation of pericardial effusion. Subsequent echocardiographic tests produced images which probably referred to valvular vegetation. As a matter of fact these findings proved to be result of the rupture of the latero-posterior tendinous cord of the mitral flap and other similar cords whose stumps, covered in fibrin, had adhered to the edge of the anterior cups. This finding was discovered during surgery, which was performed early and successfully, and was followed by excellent long-term results. PMID- 2093853 TI - [Cardiological aspects of pregnancy in women with tetralogy of Fallot. Description of a case of multiple pregnancies and review of the literature]. AB - A case report concerning a patient who received a late surgical correction of a tetralogy of Fallot, at the age of 26, and then had the chance of two pregnancies with no or little risk. The patient was severely cyanotic (erythrocytes 6,440,000/ml-Ht 58.3%-Hb 19.5 g/100 ml) with balanced pressures between the two ventricular cavities and 72 mmHg gradient between right ventricle and pulmonary artery. Before the operation two pregnancies resulted in abortions: the former was before the correction of the cardiac malformation and the latter just after. Then two pregnancies were successful and both the newborn males were healthy and completely free from congenital diseases, and in particular cardiac. Brief examination of literature. PMID- 2093854 TI - [Ischemic cardiopathy in young athletes. Description of 3 cases]. AB - Over age 30, coronary artery disease is the most frequent cause of sudden death in athletes. Adequate medical controls are important to avoid this event, especially in sport activities that place repeated loads on the cardiovascular system. Even well trained athletes are vulnerable to such events. Superior athletic performance does not exclude ischemic cardiomyopathy. Three cases of ischemic cardiomyopathy in young athletes are reported. PMID- 2093855 TI - Detection of serum antibodies against Borrelia burgdorferi with some commercially available serological tests. AB - Sixty-three sera were analysed for antibodies against Borrelia burgdorferi with an in-house indirect immunofluorescence assay. Thirty-nine sera were positive (titer greater than or equal to 256), seven borderline (titer 128) and 17 negative (titer less than or equal to 64). These results were compared with results obtained with four different commercial assays for detection of such antibodies. Indirect immunofluorescence tests yielded most positive results. The flagellin ELISA test detected antibodies in patients with erythema chronicum migrans (ECM) more often than the other test systems. Sera from patients with acrodermatitis chronica atrophicans (ACA) were positive in all systems. The serological diagnosis of borreliosis is difficult and direct methods for detecting the presence of the microbe are highly needed. PMID- 2093856 TI - Some arguments on early hospital admission and treatment of suspected meningococcal disease cases. AB - Arguments are presented which indicate or show that: (1) Diagnostic precision and severity level of systemic meningococcal disease (MCd) both seem to rise exponentially with the developmental stage of the disease at referral. Lowering of the clinical admission threshold improves early coverage of vaguely suspected cases and should probably be implemented in Norway. (2) Fear that cell wall active bactericidal antibiotics could trigger important endotoxin release may cause unnecessary treatment delays. (3) Although risk of death due to meningococcal septicemia is the main indication for early treatment of MCd, the risk of sequelae may also become a major cause for very early treatment of MCd. (4) Treatment delays for MCd cases could have been substantially reduced by implementing reasonable guidelines. (5) In the relations between the public and the health service both organizational and psychological factors are operating. (6) Increased awareness among professionals and lay people of some key symptoms and signs may facilitate earlier diagnosis of MCd. (7) Earlier treatment of meningococcal disease is now feasible and does seldom preclude the possibility of etiological diagnosis. (8) More relevant studies and information on the early phases and rapid management of MCd are highly desirable. Rapid diagnosis and treatment of MCd are very important to reduce death, sequelae and community costs and should be more advocated in training of health personnel and in public information. PMID- 2093857 TI - [Primary plasty of deep flexor tendons during complicated injury of hand]. AB - In treatment of recent associated damages of finger flexor tendons and nerves the authors have developed the methods of primary-single-stepped and prumary-two stepped restorative operations, including reinsertion, plasty or endoprosthetics of deep flexor tendon in combination with microsurgic epineural suture. It has been utilized an atraumatic silicon tendon endoprosthesis of proper construction. Excellent functional results of treatment have been obtained in 52.5% of observations, good--in 21.9%. PMID- 2093858 TI - [Outcomes of the therapy of old injury of finger flexor tendons]. AB - 193 fingers of 131 patients have been treated at the level of the I, II and III zones due to inveterate tendon damages. In case of isolated damage of deep flexor tendon of the II-V fingers at the level of the I zone there were made palliative operations of 12 fingers: tenodesis and arthrodesis of distal interphalangeal articulation in functionally advantageous position. They failed to achieve successful outcome with one finger. In 17 cases long flexor tendon of the I finger had been restored by different methods; in all cases there were achieved good and excellent outcomes. Three fingers (IV, V) with the tendon, damaged at the II zone level, were subjected to plasty by free autotransplant. The outcomes are as follows; satisfactory--2, bad--I. At the remaining 161 finger (II-V) deep flexor tendon has been restored by different methods with utilization of autotendon with its natural blood circulation or revascularized one. There was formed an artificial tendon sheath in some methods. Positive outcomes, as evaluated by the system of the American association of hand surgeons, were achieved in 138 (85.7%) cases, by Buch-Gramcko system--in 143 (88.8%) cases. PMID- 2093859 TI - [Osteoplastic operations in the treatment of tumors of finger phalanx bones in children]. AB - In the article is proposed the method of treatment of finger phalanx tumors in children, localized in the area of growth zones. By application of the proposed method the authors operated on 12 children aged 3-15 years in connection with the benign tumors of finger phalanx bones. Long-term results were followed up with all patients during 1-5 years. There was achieved complete restoration of the anatomic structure of bone; no growth delay was observed. Finger functions are completely restored. PMID- 2093860 TI - [Lateral shoulder graft for microsurgic plasty of hand and foot]. AB - The authors have thoroughly studied the versions of anatomic structure, peculiarities of blood circulation and innervation of lateral arm graft at 20 recent cadavers. The graft can be utilized in different modifications; cutaneofascial, subcutaneofascial, musculocutaneous, osteocutaneous. In the clinic were made 8 free microsurgic transplantations of lateral arm graft for plasty of tissues of different genesis in functionally important zones of hand and foot. In long-term post-operative period all patients demonstrated good functional and cosmetic results. PMID- 2093861 TI - [Microsurgical autotransplantation in the correction of post-traumatic foot defects]. AB - In the article is analyzed the experience of treatment of 211 patients with traumata, which are the results of thermal and irradiation foot injuries. 30 patients were subjected to microsurgical reconstruction with application of complex of tissular transplants. There were differentiated 3 types of foot tissue injuries, determining transplants and operative technique selection. It has been determined that the closure of ulcerous defects in case of post-thrombotic disease is possible with utilization of radial graft of forearm on long venous pedicle. Prevention of venous anastomosis thrombosis is contributed to by formation of peripheral arteriovenous anastomosis in the transplant. Impartment of the points of fixation of the muscular part with the locomotive nerve suture contributes to the increase of adequate reliability of musculocutaneous graft. Utilization of osseous transplant of iliac crest allows to perform an orthopaedic correction of the lost anterior part of foot and prevents limb amputation. PMID- 2093862 TI - [Diagnosis and therapy of Achilles tendon injuries]. AB - On the basis of voluminous clinical material (218 patients) the authors consider the peculiarities of diagnosis and treatment of victims with Achilles tendon damages. The authors pay special attention to the thorough clinical investigation of patients, indicate the importance of early diagnosis and opportune operative treatment. The authors present the basic principles of surgical tactics which ensure correct approach to the selection of operative treatment in case of Achilles tendon rupture. There are analyzed long-term results of treatment of 161 patients with Achilles tendon injuries. PMID- 2093863 TI - [Application of "Aekol" preparation for combined treatment of open injuries]. AB - Therapeutic effect of "Aekol" preparation (artificial sea-buckthorn oil) has been studied in the process of treatment of 41 victims and patients with open injuries of limb segments, pyo-necrotic complications of skeletal trauma, investing tissue necrosis following cavitary and cutaneoplastic operative interventions, tropic disturbances of investing tissue integrity. "Aeko" preparation efficiency has been compared with the efficiency of prototype preparation (natural sea-buckthorn oil) and with the efficiency of remedies, traditionally applied for the II phase of the wound process. On the basis of clinical observations, wound surface planimetry, investigation of wound surface bioptats and study of dynamics of some biochemical components in the blood serum in the process of wound healing the authors concluded that the clinical efficiency of "Aekol" preparation in open injure treatment is comparable with the efficiency of natural sea-buckthorn oil and considerably exceeds the efficiency of the traditional would healing remedies. PMID- 2093865 TI - [Extracorporeal connection of heterologous spleen (ECHS) in the combined intensive therapy of sepsis]. AB - Biohemosorption by means of extracorporeal connection of heterogeneous spleen renders not only powerful detoxic action, but intensive immunomodulation action as well. Swine spleen used for biohemosorption possess high bacterisorptive and immunomodulating potential. The cases of persistent course of disease, development of antibacterial therapy, grave condition of a patient serve as an indication for application of extracoproreal connection of heterogeneous spleen within the complex of intensive therapy. During 1989 in the hospital were treated 9 patients with osteomyelitis and extensive suppurative foci of soft tissues of the locomotor apparatus, complicated by severe sepsis. Those patients were applied to totally II extracorporeal connections of heterogeneous spleen and 8 biohemosorptions by means of heterogeneous spleen sections. In general, intensive therapy with application of extracorporeal connection of heterogeneous spleen was effective enough. All patients with no exception left hospital in satisfactory condition in 28-56 days after the beginning of treatment. PMID- 2093864 TI - [Treatment of decubitus ulcer by "Algimaf" preparation]. AB - The process of treatment of 20 spinal patients with 26 decubituses of different localization by means of applications of alginatous coating "Alghimaf" has been observed. The results of treatment are as follows: 22 wounds healed with formation of soft elastic cicatrix, 2 patients have been discharged from hospital with actively epithelializing wounds, 2 patients were subjected to epidermatoplasty. The method of control: chnic observation, planimetry, citologic, microbiologic investigations. It has been demonstrated "Alghimaf" efficiency in treating of decubituses. PMID- 2093866 TI - [Plasma fibronectin in experimental combined mechanical trauma, complicated by disseminated intravascular coagulation]. AB - Hemocoagulation system state and plasmatic fibronectin level at experimental associated craniocerebral trauma have been studied at 29 mongrel white rats (males). It has been revealed that associated craniocerebral trauma, complicated by disseminated intravascular blood coagulation, is accompanied by reliable decrease of plasmatic fibronectin concentration. It has been established that hypofibronectinemia has temporal coincidence with the reaction of hemocoagulation system on trauma and direct quantitative correlation with the decrease of coagulating fibrinogen level and fibrinolytic system activation. PMID- 2093867 TI - [Combined examination of patient with arthrogryposis]. PMID- 2093868 TI - [Unusual cervical rib]. PMID- 2093869 TI - [Abnormality of extensor digitorum brevis manus]. PMID- 2093870 TI - [Correction of equinus deformity component in congenital clubfoot in children]. PMID- 2093871 TI - [Basic principles and methods of aid to patients with severe hand trauma]. AB - Aid rendering to the patients with severe hand trauma is presented as a system of primary-reconstructive treatment, including individual approach to the surgical aid tactics, terms and volume selection, where the defining factors are the state of tissue blood circulation, application of the complex of conservative and operative measures aimed at the prophylaxis and therapy of circulatory and infectious complications, selection of rational methods of the lost anatomic formations reconstruction. There are described clinical criteria of tissue vitality evaluation and those obtained with application of instrument methods (infrared thermography, electric resistance thermometry, ultrasound indication of blood flow). If the state of the damaged hand tissues requires medicinal treatment it would be expedient to carry out the primary-postponed treatment, consisting of 2 stages. The first stage includes surgical manipulation, aimed at microcirculation improvement and wound surface isolation by means of watertight cover. The second stage is the final one. Its volume depends upon the compensation of tissue blood flow and is carried out for 2-5 days in planned order. PMID- 2093872 TI - [SMF-radiothermometry in Albers-Schoenberg disease]. PMID- 2093873 TI - [Surgical treatment of congenital clubfoot in children]. PMID- 2093874 TI - [Double rotatory osteotomy in dysplastic coxarthrosis in adults]. PMID- 2093875 TI - [Characteristics of everyday injuries]. PMID- 2093876 TI - [Treatment of open fractures and dislocations of hand long bones]. AB - Efficiency of different fixation methods of open fractures and dislocations of hand tubular bones on the basis of treatment experience of 206 patients has been investigated in clinical conditions. Immobilization with a plaster bandage, osteosynthesis and transarticulation fixation by wires, osteosynthesis by external fixation apparatus were used. An analysis of long-term results of treatment of 128 patients demonstrated that fixation of damaged bones and joints by the external fixation apparatus is the most effective one. PMID- 2093877 TI - [Arthropathies related to HLA-B27]. AB - Spondyloarthropathies represent an important problem within the field of chronic childhood arthropathies. Nosology and differential diagnosis are yet unclear. It is important to distinguish spondyloarthropathies from JCA because biological aspects of affected patients, clinical findings, extraarticular manifestations and prognosis are very different. Ankylosing spondyloarthritis is the prototype of spondyloarthropathies: at the beginning, axial involvement is rare; it may develop during the following years or it may not occur. Enthesopathy is an important finding of spondyloarthropathies. Diseases with joint involvement, HLA B27 related, as ankylosing spondyloarthritis, psoriatic arthritis. Reiter's syndrome or arthritis associated with chronic bowel disease, enter the chapter of spondyloarthropathies. Children with familial history of spondyloarthropathies showing enthesopathy, "sausage fingers" and with the presence of HLA B27, may be classified in the group of spondyloarthropathies. Children with a chronic arthritis with pauciarticular onset, B27 positive, without any sign and finding spondyloarthropathies, should be classified as JCA from the beginning. A follow up of children affected with chronic arthritis is fundamental for a more correct classification of the disease. PMID- 2093878 TI - [Systemic lupus erythematosus in childhood: review of the literature and personal observations on 32 cases]. AB - The main clinical features as well as the most important laboratory test in systemic lupus erythematosus (SLE) are reviewed. The peculiar aspects both in clinical presentation and in natural history of this disease in childhood are stressed. Personal experience is reported: 32 cases, 8 males and 24 females, mean age of onset 10.9 + 2.1 yrs, are evaluated. The most frequent clinical symptoms at diagnosis were fever, skin involvement and joint involvement, while anemia, nephropathy and hepatosplenomegaly were frequently present at onset. ANA were detected in all the subjects, anti dsDNA in 84% of cases; in only one patient SS A/SS-B assayed positive. C4 was decreased in 17/32 cases at onset, in the others during the course of disease. Three patients died, 2 for infections, 1 for a non Hodgkin lymphoma. Two cases present a chronic renal failure (1 is dialyzed). PMID- 2093879 TI - [Juvenile dermatomyositis]. AB - Juvenile dermatomyositis (JDM) is a chronic multisystem inflammatory disease that primarily involves skin and muscles. The clinical picture is mainly characterized by the typical cutaneous rash and by skeletal muscle weakness. Nevertheless the vasculitic process may extend in some cases to other organs such as lung, joints or gastrointestinal system. Calcinosis represents a relatively frequent complication of JDM and occurs in most cases during the late stage of the disease. Usually serum levels of muscle enzymes are elevated and electromyography shows signs of myositis. Muscle biopsy is generally performed only in doubtful cases. JDM should be differentiated from the muscle involvement of other diffuse inflammatory connective tissue diseases and from non inflammatory myopathies. The treatment is mainly based on steroids, whose dosage and regimen depend on disease severity. Steroid therapy has greatly improved the prognosis of JDM. PMID- 2093881 TI - [IgA deficiency in pediatrics]. AB - To evaluate the IgA deficiency we have considered 368 children, admitted to "Day hospital" for different pathologies: 64 of them had serum IgA levels lower than the normal values for their age according to Ellis and Robbin. The age of the children with this deficiency was included from 4 months up to 8 years: 39 were boys, 25 were girls. In 54 cases the IgA deficiency was "partial" that is: the IgA value found out was lower than the normal for the age, but higher than 5 mg%. In 10 cases the IgA deficiency was "severe" (the IgA value was lower than 5 mg%). Six cases, among the 29 ones with intestinal diseases, had a severe deficiency, whereas among the 22 cases with respiratory diseases 3 had a "severe" deficiency. The 2 patients with urinary disease had a partial deficiency; only one case of the remaining 11 with different pathologies had a "severe" deficiency. Among the carriers of serum IgA deficiency an high incidence of chronic pathology has been found out (83%). Nevertheless the percentage of IgA deficiency extrapolated from the all case histories doesn't differ very much (64 cases among 368 = 17.39%) considering only those patients with chronic relapsing pathology (53 cases among 275 = 18.2%). Therefore it seems that the IgA deficiency could be considered a chronicizing factor in the examinated pathology even if in few cases. Anyway the frequency of IgA deficiency has reached major values (29/54; 45.3%) in the patients with enteric diseases. The frequency of IgA deficiency is smaller but still important in those patients with respiratory diseases (22/64: 34.3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2093880 TI - [Systemic sclerosis in childhood]. AB - Systemic sclerosis is a multisystem disease of unknown cause, characterized by inflammation, vascular and fibrotic changes with excessive accumulation of connective tissue. The lesions may involve the skin and various internal organs (kidney, lung, gastrointestinal tract and heart). The first symptom is usually Raynaud's phenomenon, followed by skin changes; at the beginning the skin is swollen and oedematous, and then becomes thick, taut, shiny and atrophic. The prognosis of SS depends mainly on the severity of visceral involvement. The treatment of SS consists of drugs that improve the microcirculation and reduce collagen proliferation, such as calcium-antagonists (nicardipine) and D Penicillamine. PMID- 2093882 TI - [Short near-fainting in children with or without loss of conscience]. AB - Short near-faints with or without loss of consciousness have different etiologies and pathogenesis and, according to these, they recur with various frequency. This subject was reported on several publications and here is again examined with the contribute of personal experience and the description of distinct cases. The following causes were examined: vagal hypertonia, digestive troubles (gastroesophageal reflux), metabolic troubles (cyclic ketosis, hypoglycemia and hypocalcemia with peculiar clinic manifestations). Among the neurological causes were examined: epilepsy, benign paroxysmal vertigos and, particularly, the so called breath-holding spells and the migraine, about that were reported a few examples of "migraine accompagnee". Among the cardiovascular causes (ischaemic cerebral crisis), -particular attention was dedicated to orthostatic hypotension syncope. A short hint about hysteria ends the exposition of psychical causes of short near-faints. PMID- 2093883 TI - [Urinary tract infections in the first 2 years of life. Usefulness of anamnesis in the identification of at risk subjects with malformation uropathies]. AB - We have retrospectively studied 101 patients with an age below 24 months consecutively hospitalized, for symptomatic urinary tract infections, in the "Ospedale dei Bambini" of Palermo and subjected to radiological studies (urography and voiding cystouretrography). We have considered if the symptoms and the clinical objectivity could have given useful indications in the choice of the patients to be subjected to radiological studies. The clinical-anamnestic data have not allowed to distinguish, among patients with U.T.I., between the individuals with an abnormal conformation those with a normal one; however they have allowed to focus our attention on patients with U.T.I. through the singling out of some symptoms such as fever, vomit, cyanosis and anomaly micturition. Another datum standing out from our study is that the beginning of the symptoms in patients with U.T.I. was more precocious if at their basis there was urinary malformation. PMID- 2093884 TI - [Hemolytic-uremic syndrome: association with vero cytotoxin-producing Escherichia coli. An epidemiological and microbiological study on possible animal reservoirs]. AB - Vero cytotoxin-producing strains of Escherichia coli (VTEC) appear to be in man associated with a range of clinical symptoms from mild non bloody diarrhoea to haemorrhagic colitis and severe haemolytic uraemic syndrome (HUS). We present two patients affected by HUS who were investigated to determine evidence of infection by VTEC. In one of the patient free fecal cytotoxin active on Vero cells was detected as well as seroconversion of VT-neutralizing antibody titre. Both children were living in the same county town, but all parents denied any animal contact. The source of infection was not identified but one child had eaten ground beef during the period immediately prior to the onset of symptoms. Epidemiological informations are presented and the results of a study on the possible animal reservoir are illustrated. Fecal cultures were performed on 38 stools specimen obtained from non diarrheal beef cattle and pork. One VT- producing Escherichia coli strain was isolated in pork faeces (20 stools sample) whereas two VTEC were found in cattle faeces (18 stool sample). PMID- 2093885 TI - [Double-blind controlled comparison of placebo and paracetamol in patients with G 6-PD deficiency]. AB - In this study are reported 17 patients with G-6-PD deficiency. These subjects have been studied with double-blind trial between placebo and Paracetamol, looking for the possible hemolysis induced from drug in these children with G-6 PD deficiency. Hemolysis had been valued by various hematological parameters (Hb, erythrocyte count, reticulocytosis, bilirubinemia, haptoglobin, hemopexin, and survival of erythrocytes marked with Cr). The results (8 cases with placebo and 9 cases with paracetamol) demonstrate that paracetamol have not induced hemolysis in these G-6-PD deficient subjects. PMID- 2093886 TI - [Language disorders in children: diagnostic, pathogenetic and developmental aspects]. AB - Several Authors report the pathogenetic factors of developmental language disorders, some clinical features, the evaluation criteria, the treatment prospects aimed also at learning disorders. 163 children with language disorders have been examined: M98, F65; range 2.8-6.2 ys, mean 5.1 ys. The study of verbal comprehension and production and the evaluation of cognitive level, of language function, of communicative abilities, of handedness was performed. The diagnostic evaluation results: uncomplicated language retardation (31.2%), developmental dysphasia (7.4%), acquired aphasia (0.6%), dysphasia/cognitive retardation (36.8%), language retardation/deafness (10.4%), stuttering (6.8%), relational disorders (6.8%). The pathogenetic features are the following: organic factors (early brain damage 51%, early otopathies 10%), environment factors (24%, partly as joined factors), emotive disorders (11%), familiarity (10%), no determinable etiology (2%). The Author remarks some therapeutic strategies and evolution prospects of the different language disorders. In order to attain early diagnosis and treatment it seems advisable to increase cognitive-linguistic examination in preschool age and to start rehabilitation services at nursery-school. PMID- 2093887 TI - [Obesity and mental disorders in childhood]. AB - The aim of the present study was to establish the prevalence and the type of psychiatric disturbances in a group of 42 obese children (18 boys aged from 6.8 to 13.8 years and 24 girls aged from 2.8 to 15.4 years; weight excess mean +/- 1SD 146.7 +/- 17.4%) and to evaluate the efficacy of a psychological approach of obesity in childhood. The children were in a normal caloric diet and they were encouraged to reach a "target weight" in a given period of time. 22 children were randomly assigned the "analyzed" group (auxological, alimentary and psychological evaluation) and 20 to the "control" group (auxological and alimentary assessment). The psychological evaluation was performed in 20 children (the parents of two children refused to give their consent) by the following tests: creative drawing test; draw a man test (Machover); draw a tree test (Koch); draw a family test (Co-man); Rorschach's test; TAT (Thematic Apperception Test) or, in the younger, the Duss's tales. The results of these psychological tests have been communicated to the patients and or parents. The children were followed for a period of 7 months. We found in 8 children (40%) personality disturbances (which were severe in two cases) and a psychological support was started. The observed main types of disturbances were depression and anxiety. Both were due to a missing harmony between their parents, to a difficult relationship either with their mother or with other children, and to the bad child's opinion of himself. In 4 subjects a psychological support associated with diet promoted a slow, progressive and continuous weight loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2093888 TI - [Implementation of a computerized pharmacological database for pediatric use]. AB - The authors present a pharmacological database to support teaching and care activity carried out in the Divisional Paediatric Ambulatory of the Catholic University of Rome. This database is included in a integrated system, ARPIA (Ambulatory and Research in Pediatric by Information Assistance), devoted to manage ambulatory paediatric data. ARPIA has been implemented by using a relational DBMS, very cheap and highly diffused on personal computers. The database specifies: active ingredient and code number related to it, clinical uses, doses, contra-indications and precautions, adverse effects, besides the possible wrapping available on the market. All this is showed on a single for that appears on the screen and allows a fast reading of the most important elements characterizing every drug. The search of the included drugs can be made on the basis of three different detailed lists: active ingredient, proprietary preparation and clinical use. It is, besides, possible to have a complete report about the drugs requested by the user. This system allows the user, without modifying the program, to interact with the included data modifying each element of the form. In the system there is also a fast consultation handbook containing for every active ingredient, the complete list of italian proprietary medicines. This system aims to give a better knowledge of the most commonly used drugs, not only limited to the paediatrician but also to the ambulatory health staff; an improvement of the therapy furthering, a more effective use of several pharmacological agents and first of all a training device not only to specialists but also to students. PMID- 2093889 TI - [Diagnostic and therapeutic possibilities of meta-iodobenzylguanidine in neuroblastoma]. AB - MIBG is taken up preferentially by neuroblastoma cells. Owing to its high concentration in the neuroblastoma lesions, *I-MIBG scan is one of the most specific and effective tools in the diagnosis and staging of the disease. For most imaging purpose 123I-MIBG is the optimal agent. A rational approach 131I MIBG has the potential for specifically delivering very large radiation doses to the malignant cells. The results obtained in more institutions are encouraging and this therapeutic modality should be included in the therapeutic strategy of neuroblastoma. PMID- 2093891 TI - [A case of idiopathic mediastinal fibrosis with fatal outcome]. AB - Particular difficulties arise when trying to classify mediastinal fibrosis and determining its etiology and clinical evolution. In this paper, the Authors describe a case of mediastinal fibrosis which was characterized by a specific clinical origins (mild fever-anemia). It was not possible to establish the real etiology of the mediastinal lesion which in the end led to an unfavourable outcome that was linked to the local development of the illness, in spite of its benign histological characteristics. PMID- 2093890 TI - [Neurologic risks caused by perinatal and neonatal problems in a provincial hospital]. AB - The study intends to value results of follow-up of risk neonates hospitalized for the period 1980-88 at Neonatal Intensive Care Unit of Bufalini Hospital Cesena and the course with time of neurologic and neuropsychological alterations, reported to the birth-rate of territory in which operates the Neonatal Intensive Care Unit. The survivor infants attended in follow up have been 419: 63 of neonatal weight less than or equal to 1500 g (group A), 117 of weight 1501-2000 g (group B), 239 of weight greater than 2000 g (group C). The follow-up provided at first 12 months of life a pediatric examination together with motoscopic examination to Milani-Comparetti every two months, at 3 years--4 years and 6 months, 7 years a pediatric examination with evaluation of Intelligence Quotient (N.E.M.I.), at last two months of 1st Primary School evaluation of acquired scholastic learning capacities by reading test of Inizan and calculation test of Meljac. Diagnosis of cerebral palsy (C.P.) has been always placed at first 12 months of life. All the survivors have been executed pediatric checks as foreseen at first 12 months of life. The subjects with CP are 26 (%); of these 13 have an I.Q. less than or equal to 70. The risk to develop CP seems to depend strictly by hypoxic perinatal stress (21/26 infants). The type of CP seems to be conditioned by neonatal weight, in particular as regards spastic paraplegia (10/12 infants of weight less than or equal to 2000 g), but hemiplegia and tetraplegia are with equality distributed (7/14 infants of weight less than or equal to 2000 g).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2093892 TI - [Cystic adenomatoid malformation of the lung: experience in 4 operated cases]. AB - The congenital cystic adenomatoid malformation (MACP), represents the congenital lung malformation most frequent in pediatric age. After examining the embryology, the treatment and the evolution of the malformation we wish to report our experience of four cases of MACP in patients 2 month, 1, 2 and 3 years of age. Lobectomy has cured all patients with the exception of one; this child had a MACP of the lung associated with Rhabdomyosarcoma and died after one and half year of chemotherapy. PMID- 2093893 TI - [An atypical case of visceral leishmaniasis]. AB - The authors report a case of infant visceral Leishmaniosis observed in their Department, that showed unusual clinical finding (absence of fever). They emphasize the current epidemiologic situation and recommend to consider the disease in the diagnosis of long term syndroms occurring without fever and with hepatosplenomegaly. PMID- 2093894 TI - [Wiskott-Aldrich syndrome: description of a clinical case]. AB - A case of Wiskott-Aldrich syndrome is reported. At 2 months of age the infant was hospitalized because of petechiae, and a low platelet count was noted (range 30.000/90.000/mmc). During his stay in the Hospital he developed pneumonia, which lasted several weeks in spite of therapy. Subsequently he presented eczema and a defect of cell-mediated immunity, and the Wiskott-Aldrich syndrome was diagnosed. A short review of clinical and functional findings in this syndrome is reported. PMID- 2093895 TI - [Neonatal scrotal hemorrhage caused by post-traumatic hemoperitoneum]. AB - The Authors describe a case of neonatal scrotal hematoma due to post-traumatic intra-abdominal hemorrhage. Differential diagnosis with testicular torsion and other causes of neonatal acute scrotum is considered and discussed. PMID- 2093896 TI - Lipid metabolism and the neonatal chicken. PMID- 2093897 TI - An overview of lipids of Candida albicans. PMID- 2093898 TI - [New strategies in the treatment of varices]. PMID- 2093899 TI - [Pseudo-occlusive stenosis of the internal carotid artery (18 cases)]. PMID- 2093900 TI - [Doppler color. Use in the study of peripheral vessels]. PMID- 2093901 TI - [Trans-cranial pulsed Doppler]. PMID- 2093902 TI - [Angioscopy and the surgical treatment of varices in the area of the external saphenous vein]. AB - The study of post-surgical relapses, by ultrasound and phlebographic examinations, shows that the difficulties in the treatment of varices of the external saphena territory are of two types: anatomical and haemodynamic. The venous endoscopy answers precisely to the requirements of the surgical treatment of varices of the popliteal space. It offers an acceptable compromise between aesthetics and efficacy, thanks to the incisions centred on the transcutaneous luminal point. It enables a per-operative control of the ultrasound-Doppler marking and the visualization of the small calibre perforating veins (less than 2 mm), not visible by ultrasound. It especially locates the deep non palpable refluxes situated above the anastomosis of the external saphenofemoral junction. The technique used is very simple thanks to the miniaturization of the equipment and the use of flexible small calibre endoscopes adapted to venous explorations. PMID- 2093903 TI - [Digital photoplethysmography (D-PPG) in phlebology: methods and clinical use]. PMID- 2093904 TI - [The anatomic basis of vascular malformations]. AB - Basing themselves on anatomical and embryological considerations, the authors suggest a distinction between angiodysplasias and abnormalities. They define the characteristics proper to these varieties and establish the bases of therapeutic inferences. They briefly recall the lymphatic malformations. Practical and therapeutic inferences. PMID- 2093905 TI - [Management of angiodysplasia of the extremities in children and adolescents]. PMID- 2093906 TI - [Hyperplasia of the saphenous vein and the initial signs of varicose disease in children]. AB - The systematic examination of 237 children, aged between 2 and 17 years, and whose mothers suffer from varicosis, has revealed the absence of varicosis in 10 of these children. Some of them belonged to the same more or less affected family. The 227 others, that is 96%, had 1 to 4 saphenae which were pathological, palpable, with hyperplastic wall, more or less turgescent outside all effort. All the 4 saphenae of 129 children, that is 54%, were hyperplastic. 35 had only three (15%), 53 had only two (22%) and 9 had only one pathological saphena (4%). The saphenous hyperplasia starts on the terminal segment and progresses, with age, from top to bottom towards the distal end to finally reach the ankle. At this level, the observation of a "signal vein" reveals the presence of a pathological hyperplasia covering all the saphena. Out of these 227 children with pathological saphenae, only 88, that is 2 out of 5, complained of functional problems of veinous insufficiency of classical or infantile nature. Moreover, 16 children, that is 7%, had visible veinous or venular dilations. Neither the Doppler nor the ultrasound examination has revealed any clear signs in the 50 children examined. PMID- 2093907 TI - [The development of varicose veins in children and adolescents]. AB - The aim of the present prospective epidemiological study was to find the genesis of varicosis in pupils of the same age group in 11 secondary schools of the town of Bochum. The studies were always carried out in the same pupils of the 5th, 9th and 13th grades (Bochum studies I, II, III). The results of the first and second studies on 518 pupils are compared. In the children aged between 10 and 12 years of Bochum study I, isolated refluxes were found at the saphenofemoral junction (internal saphenous vein 2.9%, external saphenous vein 0.2%), but no varicose vein was yet visible at the trunk level or that of the lateral branches. In the adolescents aged between 14 and 16 years of Bochum study II, the number of refluxes of the internal and external saphenous vein had greatly increased, and isolated varicose veins were found at the trunk level or that of the lateral branches, as well as insufficient perforating veins. The varicose veins visible at the trunk level are obviously preceded by the refluxes. For the first time, an easily detectable preclinical sign offering new perspectives for a primary prophylaxis in thus available. Discrete reticular varicose veins were already found in Bochum study I (10.2%). A photoplethysmographic discrimination between the normal results and the various forms of a starting varicosis revealed in the course of Bochum study II has not been possible. Up to now, no statistical proof of a family taint has been established. PMID- 2093908 TI - [The role and practical application of a diagnostic test using papaverine in erection dysfunction]. AB - The intracavernous injection of papaverine for diagnostic purposes in the impotent subject can facilitate the velocimetric exploration of the penile arteries and may induce a rigid erection which may have a therapeutic application. This simple procedure does however necessitate prudence and experience. In particular, the dose injected and the site of injection are subject to precise criteria. PMID- 2093909 TI - [The treatment of prolonged erection after intracavernous injection of a vasoactive drug]. AB - The intracavernous injection of a vaso-active drug may induce an erection lasting for over 3 hours. The physician must carry out a simple procedure: an evacuatory puncture, which results in immediate detumescence of the penis and spares the patient any complications. PMID- 2093910 TI - [Results after a multidisciplinary study of 326 patients with erection dysfunction]. PMID- 2093911 TI - [A critical study of the penile Doppler test. Considerations apropos of a personal series of over 850 patients tested for the evaluation of impotence since 1983]. AB - The penial Doppler is, in 1990, the first intention examination the most asked for when there is a suspicion of a vascular origin in an erection problem. In fact, due to the technical difficulties to carry it out, this examination presents many uncertainties in its interpretation, and can even be the source of diagnostic errors. The aim of this study is to argue in favour of a systematic intracavernous injection of 8 mg of papaverine when the penial Doppler is carried out, enabling an increase in its diagnostic value and often a therapeutic orientation straightaway. PMID- 2093912 TI - [New and future major antithrombotic agents in venous pathology]. PMID- 2093913 TI - [Mesenteric ischemia of venous origin. The value of early computed tomography]. PMID- 2093914 TI - [Prostaglandin E1. Its pharmacologic properties. Is it a good antithrombotic agent?]. PMID- 2093915 TI - [Coumarin necrosis]. PMID- 2093916 TI - [Round table on the treatment of deep venous thrombosis. Medical treatment in a hospital setting]. PMID- 2093917 TI - [Round table on the treatment of deep venous thrombosis. Surgical possibilities]. PMID- 2093919 TI - [Round table on the treatment of deep venous thrombosis. The experiences in our phlebology department]. PMID- 2093918 TI - [Round table on the treatment of deep venous thrombosis. Review of the international literature]. PMID- 2093920 TI - [Round table on the treatment of deep venous thrombosis. Ambulatory treatment of deep venous thrombosis]. PMID- 2093921 TI - [Round table on the treatment of deep venous thrombosis. Surgical treatment of deep venous thrombosis]. PMID- 2093922 TI - [The treatment of deep venous thrombosis. Thrombolysis vs heparin]. AB - Acute and subacute deep venous thrombosis can be followed by two serious complications: pulmonary embolism feared in the early stadium and the postthrombotic syndrome (PTS) as a late complication. After a lapse of months and years there might appear a complete or incomplete recanalization, but the valves of the veins will be destroyed. Therefore it is understandable to strive first an active therapy as thrombectomy or thrombolysis to remove thrombosis. There will be released a physiological tissue plasminogen activator from the endothelium of the vein increasing a local fibrinolytic activity. But it is not strong enough to reopen the occlusion within a few days. This is only possible adding exogenous activators as streptokinase, urokinase and recently rt-PA. Heparin is well known at low-dose subcutaneously for thrombosis prophylaxis. The high doses of heparin infusion intravenously with 30-40,000 units daily are used "therapeutically" inhibiting growth-promotion of the thrombus and reducing the incidence of pulmonary embolism markedly. In respect of a postthrombotic syndrome (oedema, leg ulcers) it needs the evaluation of the early and follow up late results and the analysis of efficiency and risk of the two models of treatment. It was necessary comparing the success rate of reopening of the occluded veins after some days and follow up 5 or 6 years in clinical studies. The reopening rate in thrombolysis was about 3 times higher than in heparin therapy. But in contrast bleeding was 3 times lower in heparin therapy. For the long term follow up, physical examination, doppler-sonography phlebodynamometry and vein occlusion plethysmography were assessed. The acute intervention, regarding treatment, turned out to be the crucial prognostic parameter. Syndromes and clinical findings did indeed correlate quite well with the outcome of fibrinolytic treatment. Postthrombotic syndrome was rare in cases with complete patency. In cases where patency was only partially or not at all achieved, postthrombotic syndrome was present to a higher degree the more central and the more extensive the remaining thrombus was. In deep venous thrombosis of the lower extremity thrombolytic therapy is recommended mostly to younger patients with acute, the popliteal and the femoral vein including thrombosis, except of contraindications. More over in each of an individual case it has to be decided whether the aggressive or conservative therapy is to prefer. PMID- 2093923 TI - [Round table on the treatment of deep venous thrombosis. Progress in the treatment using heparin]. PMID- 2093924 TI - [Verification of the efficacy of sclerosing treatments in phlebology]. PMID- 2093925 TI - [Verification of sclerosing treatment of varices]. PMID- 2093926 TI - [Criteria of the verification of the efficacy of surgery in venous disorders]. PMID- 2093927 TI - [Verification of the efficacy of compression]. PMID- 2093928 TI - [Verification of the efficacy of compression]. PMID- 2093929 TI - [Late results and the frequency of new varicose formations after complete varicectomy. Analysis over a period of 17 years]. PMID- 2093930 TI - [Efficacy of vasoactive agents in clinical practice]. PMID- 2093931 TI - [Pharmacology. Therapeutic verification]. PMID- 2093932 TI - [Surgical treatment of post-thrombotic syndrome]. AB - The authors present the study of the surgical treatment of the post-thrombotic syndrome, with the different methods related to this type of pathology. The personal classification carried out by the authors (RS) includes the different pathologies and their syndromes. In the non recanalized PTS, the authors use the Palma technique (17) with temporary arteriovenous fistula, with the Siano Quiros technique (24). In the case of avalvular recanalized PTS, the authors use the Queral technique (37) using a venous by-pass, the Kistner technique (36), a personal technique consisting in an intraluminal valvuloplasty at the level of the femoral and popliteal veins. PMID- 2093933 TI - [Interaction between collagen and various vasoactive agents. Effect on in vitro fibrillogenesis of collagen]. PMID- 2093934 TI - [The effect of various extracts of Ginkgo biloba on the response of lysosomes to free radicals and to osmotic shock]. PMID- 2093935 TI - Pharmacological actions of Y-24180: I. A potent and specific antagonist of platelet-activating factor. AB - The ability of Y-24180, 4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]- 6,9 dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a] [1,4]diazepine to inhibit platelet-activating factor (PAF)-induced reactions was investigated. Y-24180 (0.0003-0.003 mg/kg, i.v.) dose-dependently inhibited PAF-induced bronchoconstriction in guinea pigs, but even at a high dose of 10 mg/kg, i.v., it was either inactive or weakly active against the bronchoconstriction induced by histamine, serotonin, acetylcholine, arachidonic acid, bradykinin, or leukotriene D4. Oral doses (0.003-0.1 mg/kg) of Y-24180 also prevented hemoconcentration due to PAF in a dose dependent manner and produced a parallel shift of the PAF dose response curve. Y-24180 (0.0003-0.1 mg/kg, i.v.) and WEB 2086 (0.03-1 mg/kg, i.v.) dose-dependently reversed PAF-induced hypotension in anesthetized rats. In mice, PAF-induced lethality was inhibited by Y-24180 and WEB 2086 with ED50 values of 0.022 and 1.42 mg/kg, p.o., and 0.023 and 0.12 mg/kg, i.v., respectively. This protective effect of Y-24180 given p.o. persisted for at least 6 hr. In actively sensitized mice lethal anaphylactic shock was prevented by oral doses of Y-24180 and WEB 2086 with ED50 values of 0.095 and 0.69 mg/kg, respectively. These results suggested that Y-24180 is an extremely potent and specific PAF antagonist with a good duration of action. PMID- 2093936 TI - Prostaglandin E2 induced changes in renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat. AB - Prostaglandin E2, when infused into the renal artery of the dog, is a vasodilator and increases both renal interstitial hydrostatic pressure and sodium excretion. Similar studies in the rat, however, have been inconclusive. The present study examined the effect of prostaglandin E2 infusion into the renal interstitium, by means of a chronically implanted matrix, on renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat. Prostaglandin E2 was continuously infused directly into the kidney interstitium to mimic endogenous prostaglandin E2 production by renal cells. The maximum change in each of these parameters occurred when 10(-5) M PGE2 was infused. Renal blood flow increased from 4.70 +/- 0.91 to 5.45 +/- 0.35 ml/min (p less than 0.05) while renal interstitial hydrostatic pressure decreased from 3.9 +/- 0.4 to 2.6 +/- 0.5 mmHg (p less than 0.05) and fractional excretion of sodium decreased from 1.02 +/- 0.20 to 0.61 +/- 0.12% (p less than 0.05). Thus, the present study demonstrates that renal interstitial infusion of prostaglandin E2 increases total renal blood flow but decreases both renal interstitial hydrostatic pressure and urinary sodium excretion in the rat. PMID- 2093937 TI - Lipid lymphocyte chemoattractants in psoriasis. AB - In view of the evidence that lymphocyte infiltrates are a constant feature of the skin lesions of psoriasis and the demonstration that certain hydroxylated metabolites of arachidonic acid are present in lesional psoriatic skin and possess lymphocyte chemoattractant properties, lipid extracts of samples from lesional and normal skin were assayed to determine which are the predominant lipid lymphocyte chemoattractants in psoriasis. Dilution-related lymphocyte chemoattractant activity was found in lipid extracts of stratum corneum samples from psoriatic lesions, but not in similar extracts of stratum corneum from the heels of normal volunteers, whereas aqueous extracts of the samples from both sources contained equivalent amounts of this activity. Subsequent purification of lesional stratum corneum lipid extracts by straight and reversed phase high performance liquid chromatography (HPLC) revealed the presence of at least two different lipid chemoattractants, one major component being identified as 12-(R) hydroxy-5,8,10,14-eicosatetraenoic acid (12[R]-HETE) by its biological and chromatographic properties. These compounds may play a role in the pathogenesis of the lymphocyte infiltrates in psoriatic lesions. PMID- 2093938 TI - Actions of endothelin-1 on prostaglandin production by gestational tissues. AB - Endothelin-1 (10(-11)M-10(-7)M) was incubated with human umbilical vein endothelial cells and cells derived from amnion and decidua and prostaglandin production was determined. The rates of biosynthesis of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) by endothelial cells were increased significantly by treatment with endothelin-1. Amnion cell PGE2 production was reduced significantly by endothelin-1 treatment whereas decidual PGE2 and prostaglandin F2 alpha production was unaffected by this treatment. Thus, it is possible that endothelins may play a part in the regulation of uteroplacental hemodynamics and the mechanisms of parturition. PMID- 2093939 TI - Increased production of ovarian thromboxane in gonadotropin-treated immature rats: relationship to the ovulatory process. AB - Thromboxane (TX) B2, a stable metabolic product of hydrolysis of TXA2, was measured by radioimmunoassay in tissue extracts of ovaries of immature rats pretreated with pregnant mare's serum gonadotropin and human chorionic gonadotropin. Ovarian concentrations of TXB2 increased before, and remained elevated after, the time of ovulation. In a subsequent study, ovulation was inhibited in a dose-dependent fashion by a reported TXA2 receptor antagonist, AH23848. Nevertheless, inhibition of the preovulatory rise in synthesis of TXB2 by furegrelate (a thromboxane synthetase inhibitor) did not prevent ovulation. Nor was the blockade of ovulation caused by indomethacin (a cyclooxygenase inhibitor) reversed by a TXA2 mimetic (U-46619). It does not appear that a preovulatory increase in ovarian thromboxane is an obligatory component of the ovulatory mechanism of gonadotropin-primed immature rats. PMID- 2093940 TI - Inflammatory and traumatic lesions of the knee and ankle: comparison of 0.23 T and 2 T MRI. AB - Fifty-six patients with traumatic and 117 patients with inflammatory lesions of the knee and ankle were examined with a 2 T (69 examinations) or 0.23 T (104 examinations) MR system. The quality of all images was assessed by the consensus of three radiologists on a scale of diagnostic (3+, 2+) and nondiagnostic (1+) image quality. More than 90% of images from both systems were diagnostic. However, the proportion of 3+ quality images was significantly higher (p less than 0.001) at the magnetic field strength of 2 T (81% = 56/69 versus 49% = 51/104 at 0.23 T). Motion artifacts were the main cause of reduced image quality independent of field strength. In patients with traumatic and inflammatory diseases of the knee and ankle, high field imaging at 2 T provided better image quality than low field imaging at 0.23 T. PMID- 2093941 TI - Traumatic fistula between internal iliac artery and external iliac vein. AB - Traumatic iliac arteriovenous fistulas (AVFs) are extremely rare, with only two cases reported in literature involving the internal iliac artery and the external iliac vein. We report the case of a 23-year-old man who sustained a gunshot injury to the left lower quadrant of his abdomen and subsequently developed unilateral leg edema of "elephantiasic proportions." Intra-arterial digital subtraction angiography six years later was essential for diagnosis and comprehension of the pathomechanism. The angiographic examination showed an internal iliac false aneurysm, as well as a high-flow arteriovenous communication between the left internal iliac artery and external iliac vein complicated by thrombotic occlusion of the left common iliac vein. The initial vascular injury and the surgical management of simple ligation were thought to be responsible for the iliac AVF and the subsequent thrombosis of the common iliac vein. On the one hand, the thrombotic occlusion of proximal vein led to a sharp increase of mean pressure in the proximal and distal arteries and in the distal vein, resulting in chronic venous insufficiency with incompetent varicose veins. On the other hand, the restriction of venous outflow produced extreme peripheral edema and large superficial veins serving as collaterals to bypass the fistula. Vascular surgery could repair the lesion by closing and bypassing the AVF. PMID- 2093942 TI - Chronic liver disease: value of volumetry of liver and spleen with computed tomography. AB - Volumetric comparisons of portions of liver and spleen were performed in patients with chronic liver diseases to determine their diagnostic value. Volumetric ratios of liver and spleen were determined by CT examination in 34 normal subjects and 125 consecutive patients with histologically proved liver cirrhosis, chronic active hepatitis, chronic persistent hepatitis, acute hepatitis, or fatty liver. Ratios of caudate lobe, spleen, and lateral segment of the left lobe of the liver to the remainder of the liver, right lobe and medial segment of the left lobe (RL+LM), were calculated. The product of caudate lobe/RL+LM and spleen/RL+LM was of value in differentiating liver cirrhosis from other liver disease, with a sensitivity of 60%, specificity of 98%, and accuracy of 86%. The same ratios differentiated liver cirrhosis and chronic active hepatitis from other liver diseases with a sensitivity of 79%, specificity of 100%, and accuracy of 90%. Volumetric ratio measurements are useful in the diagnosis of cirrhosis and chronic active hepatitis. PMID- 2093944 TI - A septum-like structure of the gallbladder in acute viral hepatitis: CT demonstration. AB - We present two patients with a septum-like structure of the gallbladder on CT. The patients were hospitalized with acute viral hepatitis. CT performed within a week from the onset of symptoms demonstrated a high density linear structure in the gallbladder mimicking a septum. This structure seemed to be produced by a marked thickening of the gallbladder wall. It disappeared during the clinical recovery. PMID- 2093943 TI - Indexes of bone mineral content on second metacarpal bone roentgenogram analyzed by digital image processing: a comparison with other bone mass quantifying methods. AB - A new photodensitometric technique (digital image processing, DIP) was performed to assess the bone mineral content of the metacarpal bone as a screening test for bone loss in 340 healthy or osteoporotic women as well as 35 steroid-dosed patients and 46 patients with chronic renal failure on hemodialysis. This procedure was compared with single photon absorptiometry and dual photon absorptiometry in terms of clinical value. Two bone mineral indexes, metacarpal index and sigma GS/D (the integrated bone mineral density of cortical and trabecular bone on a cross section in the middle of the second metacarpal bone), were equal to other methods in the quantification of decreases in bone mineral content due to aging in healthy or osteoporotic women. In addition, sigma GS/D was sensitive enough to detect decreases in bone mineral content in patients with vertebral fractures, on steroid therapy, and with chronic renal failure. Thus, sigma GS/D measured by DIP was shown to have clinical value as a tool in screening for decreased bone mineral content. PMID- 2093945 TI - Routine calibration of brachytherapy sources with a well-type dose calibrator using standard calibrated sources. AB - Brachytherapy, which refers to short-distance treatment via implanted sources, requires an accurate knowledge of the dose distribution in the implant volume. A critical step in the determination of the dose distribution involves an accurate calibration of brachytherapy source strength. Following the guidelines recommended by AAPM Task Group No. 22, a routine calibration procedure for brachytherapy sources 137-Cs, 192-Ir, and 125-I has been developed. The calibration of sources is performed with a well-type dose calibrator using standard calibrated sources obtained from the American, British, and French national laboratories. Selected characteristics of the dose calibrator are reported, and some of the problems associated with the dose calibrator are discussed. The results of a comparison of the calibrated sources from the three national laboratories are presented. PMID- 2093948 TI - Department of Health and Human Services, Public Health Service, National Institutes of Health. Human Gene Therapy Subcommittee. Minutes of Meeting, June 1, 1990. PMID- 2093946 TI - Adjuvant internal hepatic radiotherapy using colloidal 32P chromic phosphate in colorectal cancer. AB - The purpose of the study is to investigate the value of adjuvant radiotherapy given in the form of colloidal chromic phosphate 32P suspension administered via portal vein, in preventing the growth of occult metastases in the liver. Twenty two patients (10 patients of treated group with 12 controls) were followed 12 months after operation. There was no significant change in the CBC and liver functions after administration of 32P labeled colloidal chromic phosphate. Although local recurrence rates were very similar in both groups of colorectal cancer (3/12 in the control group and 4/10 in the treated group), liver metastasis rates were quite different: 4/12 in the control group and none (0/10) in the treated group. In conclusion, 32P labeled colloidal chromic phosphate is expected to prevent liver metastases of completely resected colorectal cancer. PMID- 2093947 TI - A comparison of swine abdominal temperature distribution after heating with BSD 1000, an annular phased array system (APAS), and Thermotron RF-8. AB - External hyperthermia for deep-seated tumors is still a difficult problem. We compared the abdominal temperature distribution in a pig after heating with BSD 1000, an annular phased array system (APAS), and Thermotron RF-8. Thirty elastic tubes were inserted into the upper abdomen of the pig and a thermocouple was inserted into each of the tubes. After heating, these thermocouples were moved at 1-cm intervals and the three-dimensional temperature distribution was obtained. The temperature distribution after heating with APAS and Thermotron RF-8 was compared by using the distribution on the longitudinal center line of each sagittal plane at 1-cm intervals from the center. The temperature was much higher and its distribution more homogeneous with APAS than Thermotron RF-8. PMID- 2093949 TI - Recombinant DNA Advisory Committee regional hearings, 1990. Written statements. PMID- 2093950 TI - Department of Health and Human Services. Recombinant DNA research; proposed actions under the guidelines. AB - This notice sets forth proposed actions to be taken under the National Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA Molecules. Interested parties are invited to submit comments concerning these proposals. These proposals will be considered by the Recombinant DNA Advisory Committee (RAC) at its meeting on October 16, 1990. After consideration of these proposals and comments by the RAC, the Director of the National Institutes of Health will issue decisions in accordance with "NIH Guidelines". PMID- 2093951 TI - Department of Health and Human Services, National Institutes of Health. Recombinant DNA research: proposed actions under the guidelines. AB - This notice sets forth proposed actions to be taken under the National Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA Molecules. Interested parties are invited to submit comments concerning these proposals. These proposals will be considered by the Recombinant DNA Advisory Committee (RAC) at its meeting on February 4, 1991. After consideration of these proposals and comments by the RAC, the Director of the National Institutes of Health will issue decisions in accordance with the NIH Guidelines. PMID- 2093952 TI - [Paralytic shellfish poisoning by Spondylus calcifer contaminated with Pyrodinium bahamense, Costa Rica, 1989-1990]. AB - This paper describes an outbreak of paralytic shellfish poisoning (PSP), affecting human populations on the Pacific Coast of Costa Rica in October 1989. Numbness in arms, face and legs occurred 30 to 45 minutes after ingestion of the large clam Spondylus calcifer. Paralysis of legs and respiratory symptoms followed, often persisting for one week. Large amounts of the dinoflagellate Pyrodinium bahamense were found in the intestine of the mollusk. A toxin was detected in crude or filtered and heated macerates of intestine, muscle, mantle and hepatopancreas of S. calcifer, and to a lesser extent Tagelus sp., by injection of its crude or diluted extracts in white mice. The effects in mice consisted in paralysis and asphyxia generally leading to death in less than 5 minutes, compatible with saxitoxin. Mice were killed by the toxin in macerates diluted 1:100 to 1:1000. No toxin was detected in Anadara tuberculosa (Bivalvia) or in peneids. Prevention rests on intersectoral actions between state and private sectors in charge of fishing, distribution and marketing of shellfish, as well as on education of the population at large. PMID- 2093953 TI - [Retrospective review of the prevalence of hepatitis B virus in several population groups]. AB - Nine different groups of individuals studied from 1969 to 1985 were tested for Hepatitis B Virus (HBV) markers. In 8 groups only HBsAg in serum was tested, in another group: tissular HBsAg, and in two of those groups: serum HBsAg, anti-HBs and anti-HBc. Mean HBsAg prevalence in groups similar to general population was 0.64%; 5% in cirrhotics; HBV prevalence in haemophiliacs was 18.87% by testing serum for HBsAg and anti-HBs; serum HBsAg prevalence in Viral Chronic Active Hepatitis was 43.24%; and Hepatocellular Cancer (HCC) group had a prevalence for HBV of 13.04% when only tissular HBsAg was tested, and 54.29% when serum HBsAg, anti-HBs and anti-HBc were tested in all patients. Costa Rica has a low HBV markers prevalence only similar to what is found in industrial developed countries. PMID- 2093954 TI - [Nitric oxide: from endogenous vasodilator to biologic mediator]. AB - This paper review the actual knowledges about the physiological role of nitric oxide, sintetized from amino acid L-arginine. The nitric oxide sintetized in the vascular endothelium has a fundamental role in vascular tone, blood flow and arterial pressure control, acting stimulating guanylate cyclase on vascular smooth muscle. Nitric oxide could be considered the endogenous nitrovasodilator. Its action on the cardiovascular system are imitated by nitroglycerine, sodium nitroprusside and related compounds. Probably the disturbance in the synthesis or release of nitric oxide may be involved in the pathophysiology of hypertension, vasospasm and atherosclerosis. Recently has been shown that nitric oxide synthesis from L-arginine also occurs in other different cells like macrophages, central nervous system, liver, neutrophils, adrenal glands, playing different biological effects. Changes in nitric oxide synthesis or action in those systems, could be related to different pathological disorders as inflammation, atherosclerosis and cancer. The found of a substance as simple as nitric oxide, let suppose that we are in the presence of a biological mediator with a very early evolutionary origin, probably widespread in all the animal kingdom, and which represents the universal transduction system for activation of the soluble guanylate cyclase enzyme. PMID- 2093955 TI - [The Fuenlabrada's study: tobacco as cardiovascular risk factor in children and adolescents]. AB - Smoking habits were studied in 1,274 healthy adolescents of both sexes, aged 10 to 18 years, of Fuenlabrada, Madrid. It was known by personal interview. 30% of the population were smokers. Smoking habits increased with age up to 18 years when 63% of males and 53% of females were smokers. Smoking prevalence was significantly higher among males than in females. Males and females smokers had significantly lower levels of C-HDL and higher levels of C-LDL/C-HDL ratio than non smokers. No differences were observed for anthropometric variables, body mass index, blood pressure, skin-fold thickness, total cholesterol, glucemia and uric acid. The implications of these findings are of concern in light of the apparently protective role of C-HDL in coronary heart disease. These findings provide valuable information to the promotion of antismoking campaigns in adolescent age. PMID- 2093956 TI - [The use of digitalis: a prospective study on the posology of digoxin with weekly interruption]. AB - The dixogin dosage with an interruption of two consecutive days a week is frequently used in our country. We decided to compare this kind of digoxin dosage with an uninterrupted one by means of describing in each case the serum digoxin level, by determining whether it is in the so-called therapeutic range (0.8-2.0 ng/ml) or not, and by correlating the serum level to the clinical response (the control of heart rate in patients with atrial fibrillation). We designed a crossover clinical trial on 14 patients taking digoxin, having normal renal function and suffering from atrial fibrillation. The serum digoxin concentration found in the weekly interruption digoxin dosage (1.02 +/- 0.23 ng/ml before and 0.66 +/- 0.15 ng/ml after) was lower than one found in the continuous dosage (1.09 +/- 0.23 ng/ml). The 25% of the patients (before the interruption) and 75% (after the interruption) had plasma levels lower than 0.8 ng/ml, in opposition to the 8.3% found in the uninterrupted dosage. No patient on the continuous dosage showed clinical and/or electrocardiographic signs of digoxin toxicity. The mean heart rate was higher in the weekly interruption dosage (74.4 +/- 11.6 beats/min before and 83.9 +/- 6.4 beats/min after) than in the continuous dosage (72.9 +/- 10.5 beats/min). In terms of achieving serum digoxin levels within the so-called therapeutic range, the uninterrupted dosage proved to be better than the discontinuous one as well as to control the heart rate. PMID- 2093957 TI - [Late potentials in patients during the hospitalization period following acute myocardial infarction]. AB - Serial signal-averaged electrocardiograms were recorded every 72 hours in 60 patients admitted to the coronary care unit with acute myocardial infarction. The prevalence of late potentials was 61.6% (37 patients) during hospitalization. Of these 37 patients, late potentials appeared transiently in 20 (54%), while in 9 patients (24%), once late potentials had appeared, they tended to persist. No specific clinical characteristics were related to the development of late potentials (site of infarction, peak creatine kinasa activity, Killip class, thrombolytic therapy). The presence of late potentials did not identify patients who developed clinically significant ventricular tachyarrhythmias (primary ventricular fibrillation, ventricular tachycardia). The abnormal late potentials were modified by the administration of lidocaine. This lack of correlations suggests that the abnormal signal averaged electrocardiogram and complex ventricular arrhythmias during acute myocardial infarction have different electrophysiological bases. Late potentials could be only a bystander electrophysiological phenomenon without clinical correlation in this clinical phase. PMID- 2093958 TI - [Echocardiographic manifestations in patients with hypereosinophilia]. AB - In order to assess the degree and type of cardiac involvement in patients with sustained hypereosinophilia, we studied by two-dimensional, M-mode echocardiography and Doppler (4 cases) 20 patients distributed into 2 groups. Group I: 10 patients with the idiopathic hypereosinophilic syndrome. Group II: 10 patients with secondary hypereosinophilia. In group I, 6 patients (60%) had echocardiographic abnormalities consistent with the endomyocardial disease: four apical obliteration of right ventricle, three apical obliteration of left ventricle, three endocardial thickening of the left ventricle, three endocardial thickening of the left ventricle posterior wall, one endocardial thickening of the right ventricle free wall, three subvalvular mitral thickening, three subvalvular tricuspid thickening, two pericardial effusion and two protodiastolic septal notch. These corresponded to 2 cases of endomyocardial fibrosis and restriction, as shown by pathological and hemodynamic study. In only 1 patient from group II echocardiographic abnormalities consistent with right apical occupation and tricuspid subvalvular thickening, with mild regurgitation detected by Doppler, were found. It was concluded that echocardiographic abnormalities are common in patients with idiopathic hypereosinophilic syndrome, even in the absence of clinical features. The development of echocardiographic abnormalities in patients with sustained secondary hypereosinophilia is exceptional and is probably related to duration of eosinophilia. Therefore, we think that echo Doppler is a fundamental investigation for the diagnosis and follow-up of these patients. PMID- 2093959 TI - [Intraoperative transesophageal echocardiography: initial experience with 60 patients]. AB - To assess the usefulness of intraoperative transesophageal echocardiography (ITE), this technique was applied in 60 non-selected cardiac patients operated on in our hospital by the surgical team. Only one case was excluded because it was not possible to introduce the probe, and no complications were observed in any patient. ITE permitted: 1) to obtain images without interruption and with no interference with the surgeons or anesthesiologists; 2) to confirm the preoperative diagnosis; 3) to facilitate the surgical approach; 4) the monitoring of left ventricular function, and 5) to evaluate the immediate results of the surgical procedures, particularly the assessment by Doppler technique of residual valvular regurgitations after valve repair. A minor but not disdainable inconvenience of ITE relates to the strategy of its application, as it requires a completely dedicated equipment and operator in the surgical area. PMID- 2093960 TI - [Massive thrombosis of the left atrium. Surgical experience with a series of 117 patients]. AB - From 1975 to 1988 we have operated 117 patients with left arterial thrombosis associated with rheumatic mitral valve disease. Seventy-seven were female and 40 male, with ages ranging from 22 to 69 years. In 75 cases (64.1%) the valvular lesion was mitral stenosis. Embolic antecedents were present in 38 cases (32.4%) and 95 patients (81.1%) were in class III or IV of the NYHA functional classification. In 48 cases we performed a mitral commissurotomy and in 51 cases mitral valve replacement, associated to left artrial thrombectomy. In the remaining 18 patients we made other valve procedures. The hospital mortality was 15 cases (12.8%), eight because low cardiac output, four because severe brain injury and three because posterior atrioventricular sulcus disruption. In 41.1% of the survivors there was serious hospital complications, standing out the incidence of 8 cases of transient neurologic accidents. We have followed 98 of the 102 hospital survivors between 10 and 140 months (mean 57 months). Three patients died in the follow-up, two of them during a reintervention because bioprosthesis disfunction and the third one during a reintervention because prosthetic infective endocarditis. Nine additional patients were reoperated because recidivant valvular lesions or because prosthetic disfunction, and two patients suffered embolic events during the follow-up. The antithrombotic therapy was abandoned in 19.6% of patients. At present 73.6% are in functional class I and 26.3% in class II. The association of left atrial thrombosis with with mitral valve disease induce a surgical morbimortality greater than usual for isolated valvular lesions, being mandatory a watchfull surgical technic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2093962 TI - [Infective endocarditis in drug addict patients]. PMID- 2093961 TI - [Results of valvuloplasties with balloon catheter in children. Follow-up using pulsed Doppler. Experience with our first cases]. AB - Our series includes the first 19 consecutive patients with pulmonary valvar stenosis who underwent balloon valvuloplasty in our hospital. All of them have been evaluated by an echo-Doppler study at different follow-up times, and in 10 patients the study was also performed prior to the dilatation. The ages ranged between 0.4 and 10 years (mean 3.5 years; standard deviation [SD] 2.53 years). The prevalvuloplasty degree of pulmonic stenosis found at catheterization was quantified as severe in 8 cases (42.11%) with a right ventricular systolic pressure (RVSP) in excess of 90 mmHg, and moderate in 11 cases (57.89%) with an RVSP from 70 to 90 mmHg. Transvalvular gradients were registered between 38 and 110 mmHg (m: 69 mmHg and SD: 15 mmHg). According to catheterization data obtained at the time of valvuloplasty, the procedure was considered ineffective in 2 cases (10.52%), scarcely effective in four (21.05%), and successful in the remaining 13 cases (68.42%). Doppler follow-up was carried out between 1.6 and 31.9 months after valvuloplasty (mean 12.9 months and SD: 10 months). Residual stenoses were estimated by Doppler as mild in 13 cases (68.42%), moderate in four (21.05%) and severe in two (10.52%). Mild pulmonary regurgitation was detected in 10 patients (52%). The 13 patients with a satisfactory result had slight residual gradients at the valvular level that had not been modified with the course of time. Of the 4 cases with a poorly effective dilatation the gradients noted by Doppler increased in three of them, being valvular in all but one in whom the obstruction was catalogued as infundibular.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2093963 TI - [Persistent truncus arteriosus. Echocardiographic study of 8 cases]. AB - Eight patients (4 male, 4 female) with persistent truncs arteriosus diagnosed by two-dimensional echocardiography are presented. Age ranged from 1 to 19 days. Diagnosis was based on the demonstration of a single vessel giving rise to the aorta, pulmonary arteries and coronary circulation. In 6 patients we were able to define the types of the truncus: in 4 patients corresponded to type I (with partial presence of aorto-pulmonary septum) and in 2 cases corresponded to type II (without existence of septum). All cases had a dilated truncus (1.13 +/- 0.06 cm, range 1.05-1.3 cm), with moderate overriding (52% range 30%-65%) and an infundibular ventricular septal defect (0.6 +/- 0.08 cm, range 0.45-0.85 cm). In 2 cases we could also demonstrate the presence of an interruption of the aortic aorta. We conclude that two-dimensional echocardiography (specially parasternal long-short axis views and subcostal for right or leftout flow tracts axis views) gives sufficient information about this cardiac malformation, which can be completed by the use of pulsed Doppler ultrasound. PMID- 2093964 TI - [Transesophageal echocardiographic diagnosis of a left atrial myxoma]. AB - We report the case of a 65 year old woman with a left atrial myxoma. The only clinical manifestation were two transient ischemic attacks of cerebral origin. The diagnosis was established by transesophageal echocardiography because of poor definition of the transtoracic approach. We comment the clinical and diagnostic features of this type of tumors, with emphasize in the value of transesophageal echocardiography. PMID- 2093965 TI - [Anomalous origin of the coronary artery in the pulmonary artery. Report of a case in adulthood]. AB - We report a 50 year old patient who was admitted because of congestive heart failure. Under hemodynamic and angiographic study she was diagnosed of anomalous origin of the left coronary artery from the pulmonary trunk. We examine the main aspects of the disease, physiopathology and treatment. PMID- 2093966 TI - [Aneurysm of the interatrial septum associated with Lutembacher's syndrome. Echocardiographic and Doppler study]. AB - The case of a patient with suspected atrial septal defect is presented. Echocardiographic-Doppler study confirms the defect associated with mitral stenosis (Lutembacher syndrome) and shows an atrial septal aneurysm through which the shunt is revealed. PMID- 2093967 TI - [Prognostic meaning of silent ischemia during exercise test in patients with coronary disease]. PMID- 2093968 TI - [Don Luis Calandre Ibanez (3/26/1890-3/26/1990)]. PMID- 2093969 TI - Pneumonia in the elderly. PMID- 2093970 TI - Altered immune status in the elderly. AB - The lung has an array of immunological defenses to protect itself against potentially invasive microorganisms, which include the immunoglobulin-rich alveolar lining fluid, alveolar macrophages, T lymphocytes, and polymorphonuclear neutrophils. Immunosenescence is a major predisposing factor to the increased incidence, morbidity, and mortality of pneumonia in the elderly. The progressive involution of the thymus gland in humans plays a pivotal role in the development of the immunodeficiency state characteristic of the older individual. Age takes its greatest toll on the cell-mediated arm of the immune system. Aged T cells are impaired in their ability to activate and proliferate in response to an antigen. This is partly due to age-associated structural and functional changes within the T cell. In addition, the ability of the T cell to secrete interleukin-2 (a cytokine necessary for the recruitment of other T cells) declines with age. The impaired antibody response of the elderly to foreign antigens, including the pneumococcal polysaccharide and the influenza vaccine, appears to be secondary to a deficiency of T helper cells. The macrophage functions well even in old age, but the recruitment of macrophages by senescent T cells is diminished. There also may be a blunted inflammatory response in the older individual secondary to impaired polymorphonuclear neutrophils chemotaxis and phagocytosis. PMID- 2093971 TI - Epidemiology of community-acquired pneumonia in the elderly. AB - The attack rate for pneumonia increases with increasing age and with residence in a nursing home. The rate of hospitalization of Halifax County, Nova Scotia, Canada, residents with pneumonia was 1 in 1,000, while for nursing home residents it was 33 in 1,000. The overall mortality rate for community-acquired pneumonia requiring hospitalization was 21.9%. Mortality was age-related: Seven percent of those 30 years of age or younger died, while 38% of those in the 81 to 90 year age group died. Comorbidities increased with increasing age from 0.73 +/- 0.81 for those 30 years old or younger to 2.75 +/- 1.47 for those 71 to 80 years of age. The most common comorbidities were chronic obstructive pulmonary disease, ischemic heart disease, hypertension, diabetes mellitus, malignancy, alcoholism, and neurological disease. The acquired immunodeficiency syndrome was a significant comorbidity among those 50 years of age or younger. Age-dependent trends were observed in the use of antimicrobial therapy: Cefamandole and aminoglycosides were prescribed more frequently with increasing age, whereas after the age of 61 years, the use of erythromycin declined. Penicillin usage was not age-dependent. Resource (hemograms, chest radiographs, blood chemistry, blood gases, and sputum culture) use peaked at the 50 to 60 year age group. PMID- 2093972 TI - Clinical features of pneumonia in the elderly. AB - Concomitant pneumonia and influenza constitute the leading infectious cause of death in the elderly and the fourth most common cause of death overall. The presence of concomitant illness and delays in diagnosis contribute to significant mortality from this disease in the elderly; senescence of the immune system seems less important in predisposition to pneumonia than the presence of concomitant illness. Delay in diagnosis is frequently secondary to the atypical presentations of pneumonia in the elderly. The usual symptoms of fever, chills, rigors, and sputum production that are present in young adults all may be absent; confusion may be the only presenting symptom. Tachypnea is frequent, but the physical examination, in addition to often being technically difficult, is not sufficiently sensitive in making a diagnosis. Leukocytosis is common, but by no means specific. Chest roentgenograms frequently show incomplete consolidation and findings are difficult to distinguish from other diseases of the elderly, such as congestive heart failure, atelectasis, pulmonary embolism, and malignancy. Therefore, clinical diagnosis requires a high index of suspicion despite atypical clinical manifestations. PMID- 2093973 TI - Intensive care management of pneumonia in the elderly. AB - Arterial hypoxemia, hypercapnic respiratory failure, hypotension, and depressed level of consciousness are the usual reasons for admitting a patient with pneumonia to an intensive care unit (ICU). Once the decision has been made to manage the patient in the ICU, age has little effect on the immediate goals of therapy, which include correction of hypoxemia, maintenance of adequate alveolar ventilation, and provision of sufficient blood pressure and cardiac output to support organ function until physiological homeostasis is restored as the pneumonia is controlled by appropriate antimicrobial therapy. Age-related decreases in physiological reserve are the major reasons specifically to consider ICU management of elderly pneumonia patients. These physiological changes increase the probability of major organ system failure with the development of pneumonia, and increase the likelihood that pneumonia will require ICU management. This has implications for the clinician regarding the selection and timing of therapeutic interventions. Unfortunately, the reduction of physiological reserve and the increased prevalence of coexistent chronic disease also result in significant mortality rates for elderly patients with pneumonia, potentially limiting the benefits of intensive care in this population. This raises a second issue: When, if ever, should intensive care not be used in the management of an elderly patient with severe pneumonia? A full discussion of the ethical issues surrounding this question is beyond the scope of this article, however, good medical ethics begin with sound medical judgment and are based upon solid clinical data. Accordingly, this article will also address the implications of age and underlying disease in the assessment of prognosis and use of the ICU in patients with pneumonia. PMID- 2093974 TI - Treatment of pneumonia in the elderly: pharmacological considerations. AB - Aging is associated with a number of physiological changes, including alterations in body mass, changes in organ blood flow, and reductions in renal function. The use of any drug in an older patient requires a knowledge of the effect of these physiological changes on the pharmacokinetics of that drug. Drugs with high renal clearance, such as penicillins and aminoglycosides, have a longer half-life in elderly patients. Erythromycin and ciprofloxacin, antibiotics that use both hepatic and renal clearance, require little or no dosage adjustment when used in older patients. Side effects and drug interactions occur much more commonly in older individuals and those antibiotics used in the management of pneumonia in the elderly are reviewed in detail. PMID- 2093975 TI - Pneumonia in the elderly: the hospital admission and discharge decisions. AB - Community-acquired pneumonia is both a common and a serious infection in the elderly population. The hospitalization and discharge decisions are among the most important management decisions physicians must make in caring for patients with this illness. Both of these decisions are important from a clinical, health services, and patient-oriented perspective. The hospitalization decision can be guided by a clinical algorithm that explicitly addresses five questions: (1) Does the patient have any life-threatening problems that require immediate stabilization (and de facto hospitalization)? (2) Does the patient have any prognostic factor(s) that increase the short-term risk of mortality? (3) Does the patient have any prognostic factor(s) that increase the short-term risk of morbidity or medical complications? (4) Does the patient have adequate functional skills or social support to allow care outside of the hospital? and (5) Does the patient require admission for a therapeutic modality or diagnostic evaluation? An affirmative response to any one of these questions indicates a need for hospitalization, whereas a negative response to all of the questions identifies potential candidates for outpatient care. The factors considered important in the hospitalization decision are also intimately related to the discharge decision. Before discharge, all acute physiological derangements should be corrected and laboratory abnormalities should be normalized or returning to baseline. All patients must be able to function socially outside of the hospital. Finally, treatment with an adequate course of antimicrobial therapy either must be completed or arranged on an ambulatory basis before discharge. PMID- 2093976 TI - Lipoid pneumonia. AB - The most common sources for lipids producing radiographic or clinical evidence of disease in the lungs are endogenous lipids and inhaled (exogenous) mineral oil. Endogenous lipoid pneumonia arises when lung tissue breaks down distal to an obstructed airway leading to the release of cholesterol and other lipids, producing airspace disease. Exogenous lipoid pneumonia occurs most frequently in the elderly following habitual mineral oil use. Many patients have no specific predisposing cause for aspiration of the ingested mineral oils. Symptoms, found in only half of the patients reviewed, include chronic cough and sputum production. Radiographically, the lesions are usually ill-defined radiopacities that mimic carcinoma of the lung. The inhaled mineral oil incites a foreign-body reaction, producing a granuloma with multinucleated foreign-body giant cells and fibrosis surrounding lipid droplets. Diagnostic strategies such as sputum examination for lipids and transthoracic needle aspiration are discussed. These procedures may help to avoid thoracotomy in elderly, often debilitated patients with lipoid pneumonia. PMID- 2093977 TI - Methods to assess the quality of care for elderly patients with pneumonia. AB - During the past several years, interest has focused on the cost and quality of health care. The elderly represent an important population to study since they are less resilient to the effects of acute illness such as pneumonia, and if they receive improper care, these patients will be more sensitive to that poor care and more likely demonstrate measurable ill effects. This article examines several methods to assess quality. The traditional method addresses the process of care or whether the patient received the appropriate care for his or her particular condition. Process of care evaluations either rely upon the subjective judgment of expert clinicians or use sets of explicitly defined criteria. A second quality assessment method examines the patient outcome, ie, regardless of the care received, did the patient get well? Each of these methods has strengths and limitations. Based upon this understanding, the article will describe a multimodality approach to the assessment of quality. PMID- 2093978 TI - [Surgical approaches to the pancreas]. PMID- 2093979 TI - [The electronic spirometer]. PMID- 2093980 TI - [Ureteral prostheses]. PMID- 2093982 TI - [Testicular prostheses]. PMID- 2093981 TI - [Penile prostheses]. PMID- 2093983 TI - [Urethral prostheses]. PMID- 2093984 TI - [Asepsis in the operating room]. PMID- 2093985 TI - [Sphincteral prostheses. Evolution of systems]. PMID- 2093986 TI - [The laser in digestive pathology]. PMID- 2093987 TI - [Any news on our plates]. PMID- 2093988 TI - [Sphincteral prostheses. Indications, technique, results]. PMID- 2093989 TI - [Orthostatic hypotension disclosing an autonomic deficit in a case of Horton's temporal arteritis]. AB - A 68 year-old hypertensive woman carried out, linked with the featuring complaints of temporal arteritis-polymyalgia rheumatica complex, an orthostatic hypotension caused, probably, by a spread immunocomplex damage. The presence of depression in Horton's Arteritis and its improvement with the complete recovery would show, perhaps, a central catecholaminergic failure. PMID- 2093990 TI - Mild thrombocytosis secondary to iron-deficiency anemia and stroke. AB - A 45-year-old woman with mild thrombocytosis secondary to iron-deficiency anemia suffered from hemispheric infarction in absence of vascular, cardiac or coagulation pathologies. The modest raise of the platelets count seemed as the sole possible cause for the cerebral infarction. We wish to emphasize the inconstant benignity of mild non essential thrombocytosis at levels less than 1 million/cu.mm. PMID- 2093991 TI - [Changes in sleep organization in two patients with progressive supranuclear palsy]. AB - Sleep-EEG of two subjects affected by Progressive Supranuclear Palsy was studied. Morphological, reduced and poorly organized sleep transients (spindles) in stage 2 and decreased REMs during desynchronized sleep were observed. The quantitative sleep analysis showed a poor and fragmented sleep with an increase of stage 1 and stage 3 and a decrease of stage 2 and REM sleep. PMID- 2093992 TI - Spinal myoclonus: case report and physiopathogenetic hypothesis. PMID- 2093993 TI - [Frequency in human environment and dispersion of Culicidae mosquitoes in an area adjacent to a primitive Atlantic plain forest]. AB - Results of peridomiciliary and forest environment mosquito catches are presented. By using the method single host, mosquitoes were identified according to blood meal and thus their dispersal was observed. Evidence was obtained for movements of Aedes scapularis, due apparently were appetential flights, as well as its permanence in peridomiciliar resting places. Occurrence in domestic animal shelters was recorded for this species. Peridomiciliar human bait catches showed regular occurrence of Ae. scapularis, Anopheles bellator, An. cruzii and Culex sacchettae, but anophelines abandoned the human environment for the surrounding forest. Feeding index showed clearly a preference on the part of Ae. scapularis for bovine hosts. The peridomiciliar frequency of Cx. sacchettae suggests a domiciliary tendency. The influence of large domestic animals in the human environment surrounded by primitive Atlantic plain forests, on the domiciliation of the sylvatic mosquitoes, is emphasized. PMID- 2093994 TI - Typhoid fever in children of low and high socioeconomic strata: comparison of hygiene habits. AB - The relationship between the hygienic habits of children who had typhoid fever (TF) who had recently begun attending school and their family group, is assessed. It is supposed that children, independently of their SES, acquired TF because of inadequate habits which facilitated the oral-fecal cycle. The sample was formed of 40 child-mother dyads: 20 of low SES (group A) and 20 of high SES (group B), the child of each of which had had TF. Results showed that the hygienic habits of children with respect to the oral-fecal cycle, their perception of school toilet cleanliness as well as the mothers' explanation of their children's hygienic habits is very similar in the two groups. The importance of these results is that the SES is seem to be irrelevant in the case of TF but that the hygienic habits of the children are of importance. Public health policy should be modified to include the teaching of proper hygienic habits (oral-fecal cycle). PMID- 2093995 TI - [A serological inquiry for the detection of antibodies against human immunodeficiency virus (HIV) in children in a general ward]. AB - The results of a serum inquiry for detection of antibodies against the Human Immuno-deficiency Virus in a non selected group of children, patients of a general pediatric ward, are reported. Of the 441 cases, the ELISA test gave a positive result for 1.1% of them. This result was confirmed by the Western-Blot or ImmunoBlot test. None of the five children who tested positive had a previous history of blood transfusion. These children's mothers showed positive results to the ELISA test. Of four cases, at least one of the parents was IV drug addicted. In every case the transmission was vertical. On the basis of these findings, it is suggested that hospital staff should take the necessary precautions when manipulating blood and secretions and it is recommended that serum inquiries be made on the wards of general hospitals in the attempt to establish reliable data on the prevalence of HIV. PMID- 2093996 TI - [Analysis of health and life conditions of the urban population of Botucatu, SP (Brazil). III. Knowledge and opinions of health professionals about symptoms of diseases, 1984]. AB - The knowledge and opinions of health professionals of Botucatu about the frequency and severity of thirteen symptoms and signs of diseases were studied with a view to comparing then with the opinions of Botucatu's urban population. Four hundred and thirty-five active health professionals (physicians, nurses, nurse aides, health workers (orderlies) and others were interviewed. Most of them were women, with ages ranging from 25 to 44. The health workers (orderlies) were the most numerous category. In general, the last five symptoms included in the form: bloody sputum, vaginal bleeding, breast lump, seizures and bloody urine, were considered less frequent and more serious as compared with the first eight symptoms: shortness of breath, fever, weakness, back pain (backache), chest pain, headache, cough and diarrhoea. Among the categories, the physicians differed from the other categories in less frequently attributing high scores to frequency and severity. The clinicians gave more value to these two factors than the surgeons for almost all symptoms. The comparison with the opinions of the laymen interviewed showed similar tendencies although the laymen regarded frequency and severity as more significant. PMID- 2093997 TI - [Mortality of women in reproductive age in the municipality of Sao Paulo (Brazil), 1986. I. Methodology and general results]. AB - The purpose of this study was to evaluate the accuracy of the death certificates of a sample of a quarter of all deaths in women of reproductive age (10-49 years) resident in the Municipality of S. Paulo, SP, Brazil, in 1986. For each death, further data were gathered by means of household interviews and from medical records and autopsy information where available. Nine hundred and fifty-three deaths were analysed, for whom there were good quality death certificates except with regard to maternal deaths an terminal respiratory diseases, the former being greatly under-reported. The official maternal mortality rate was 44.5 per 100,000 live births but the true rate was 99.6 per 100,000 live births. The three main causes of death were cardiovascular diseases, neoplasms and external causes. A great proportion of smokers was found among the deceased women (40.4%). Eleven percent of the deceased consumed large amounts of alcoholic beverages regularly. PMID- 2093998 TI - [Socioeconomic factors associated with postneonatal mortality in Cuba]. AB - Economic and social risk factors for both postneonatal and exogenous mortality are evaluated for Cuban children for 1982. A national sample of children who died before their first year of age (cases) and a sample of survivors (controls) was selected for the study. A logistic regression approach was used to estimate relative and attributable risks. Probability of dying when specific factors are present was computed. Results point to the lack of sanitary installations within the house and overcrowding (three or more persons per room) as the most relevant risk factors for both postneonatal and exogenous mortality. It was also confirmed that the postneonatal component is an area deserving of attention the quest for in further reduction in infant mortality in Cuba. PMID- 2093999 TI - [The occurrence of abortion in inpatients at urban center hospitals of the state of Sao Paulo, Brazil]. AB - Certain characteristics--biological, demographical, social and institutional- based on data collected from the recorded case histories of 2,588 women suffering complications after abortion, attended in a hospital of Santo Andre, an industrial urban area of Greater S. Paulo, State of S. Paulo, Brazil, in the period from January 1978 to December 1982, are identified Data show a two-fold increase in the number of women with complications after abortion over the period studied, rising progressively from 302 in 1978, to 672 in 1982. However, the number of births attended at the same hospital underwent an increase of only 14% in the same period, resulting in an average abortion/birth ratio of 1:3.6 and 1:1.8 in 1978 and 1982, respectively. The majority of the population under study (60%) professed non-skilled occupations. Age presented a statistically significant relationship with martial status, colour, profession and gestational results. A significant relationship was also observed between age at first menstruation, age at first sexual relationship and age at first pregnancy among those women belonging to the primigesta group. PMID- 2094000 TI - [The elderly population in Rio de Janeiro (Brazil): a pilot-study of confiability and validity of the mental health segment of the BOAS questionnaire]. AB - A first step in the pilot-study undertaken as part of a research project on psychiatric morbidity--depression and organic brain syndrome--in the elderly population of Rio de Janeiro is described. The main objective is to "fine-tune" the instrument used (check list of DSM-III) and testing validity of the BOAS questionnaire (Brazilian version of Short-Care). The methodological aspects, and conceptual definitions are focused as well some procedures for the next stage of the project are suggested. PMID- 2094001 TI - [Methodologic proposals for domiciliary surveys with aged populations]. PMID- 2094002 TI - [Evaluation of larval development of Anopheles darlingi (Diptera-Culicidae) raised in the laboratory on different diets]. AB - Three diets for A. darlingi larvae were tested in order to arrive at the following parameters indicative of development in this phase: length of time, both for overall as for each stage of evolution and daily and total stage survival. A methodology which combined two vital statistical methods of analysis, adjusted to the study of populations under laboratory conditions, was used for determining these parameters. The length of time for overall and for each stage of, evolution were graphically assessed on the basis of trend curves of colony median stages, in sequential surveys. Values for the total and the daily stage survival were stimulated from survival tables. Results permitted the selection of the most adequate diet for the larval development as that composed of one part of fish flour to two parts of bread flour and two parts of a heat germ, giving an average length of 12.9 days between the first larval stage and the emergent adult. Total survival rate was of 95%. PMID- 2094003 TI - Scanning electron microscopic studies of the oral tissue responses to dental implants. AB - Scanning electron microscopy (SEM) and its associated technologies have proven invaluable in elucidating the interfacial oral tissue responses to dental implants. Since the dental implant must extend from the mandibular or maxillary jaw, through the oral mucosa, and into the oral cavity, these tissue responses include epithelium, connective tissue and bone. The continual occlusal forces acting upon these tissues reinforce the dynamic character of these tissue responses. Immediately upon implantation, a healing phase begins as a response to the implanted biomaterial. Following this immediate response a longer healing phase occurs, beginning approximately 1 week after implantation, resulting in the modeling of bone to the implant as well as the formation of epithelial attachment to the implant. This later, delayed healing continues throughout the lifetime of the implant since these tissues must die and be replaced by similar tissues. Current dental research employing scanning electron microscopy is now documenting these tissue responses. This paper reviews, in detail, SEM observations of these tissue responses. PMID- 2094004 TI - Ultrastructural investigations of the bone and fibrous connective tissue interface with endosteal dental implants. AB - The interface between the tissues of the oral cavity and ceramic and titanium cylindrical endosteal dental implants was investigated with correlated light microscopy, transmission electron microscopy and scanning electron microscopy. This study suggested that mandibular bone can directly interface and form an intimate association with one-stage endosteal dental implants. This potential attachment matrix is composed of a composite of calcified bone, and an osteoid unmineralized matrix in association with an apparent osteogenic connective tissue. Further, results from this study suggested that at a level inferior to the junctional epithelium, and superior to the level of crestal bone, fibrous connective tissue can attach to the dental implant. This non-loadbearing attachment of gingival connective tissue could, by contact inhibition, prevent apical epithelial migration. In association with previously documented epithelial attachment, such apical support and connective tissue attachment appears to suggest that endosteal dental implants can be adequately maintained in the oral cavity. PMID- 2094005 TI - Scanning electron microscopic quantitative study of changes with age in closing pattern of openings of dentinal tubules on worn occlusal surfaces of Japanese permanent mandibular incisors. AB - Age-related changes in the closing of dentinal tubules of Japanese permanent mandibular incisors were surveyed using a non-destructive replication technique suitable for SEM analysis at the magnifications of up to X3,000. The areas of openings of dentinal tubules on occlusal surfaces decreased significantly between a 20-39-year age group and a 40+ age group, but the number of the openings tended to decrease. Heavy toothwear on occlusal surfaces of these Japanese permanent incisors was evident even at 27 years of age. A subject of 30 years of age showed surprisingly small number of the opening of dentinal tubules on occlusal surface. The occlusal surfaces became smoother in 40-59-year age group as closure of dentinal tubules of openings increased. Early heavy toothwear and early closure of the openings of dentinal tubules may be related to Japanese ethnic diet such as dried hard sardines whole which contain hard bones. Japanese often crush shells of crabs and shrimp with their incisors and canines as they eat. PMID- 2094006 TI - Digital correlation of ion and optical microscopic images: application to the study of thyroglobulin chemical modification. AB - A method has been developed in order to digitally correlate ion and optical microscopic images of the same sample areas. Serial cross-sections of human thyroid tissue were analyzed by secondary ion mass microscopy and by light microscopy. The resulting chemical and immunochemical map images were superimposed and correlated by means of a two-pass registration algorithm which allows to correct for geometrical distortions introduced by the ion microscope. Results are presented for the study of thyroglobulin chemical modification in pathological thyroid tissue that demonstrates heterogeneous molecular activity. PMID- 2094007 TI - Backscattered electron imaging and windowless energy dispersive x-ray microanalysis: a new technique for gallstone analysis. AB - Scanning electron microscopy with or without conventional energy dispersive x-ray microanalysis is currently used to identify gallstone microstructure and inorganic composition. Organic calcium salts are among many biliary constituents thought to have a role in gallstone nidation and growth. However, current analytical techniques which identify these salts are destructive and compromise gallstone microstructural data. We have developed a new technique for gallstone analysis which provides simultaneous structural and compositional identification of calcium salts within gallstones. Backscattered electron imaging is used to localize calcium within cholesterol at minimum concentrations of 0.01%. Windowless energy dispersive x-ray microanalysis produces elemental spectra of gallstone calcium salts which are qualitatively and quantitatively different. These combined techniques provide simultaneous structural and compositional information obtained from intact gallstone cross-sections and have been used to identify calcium salts in gallstones obtained at cholecystectomy from 106 patients. PMID- 2094008 TI - Characteristics of granulation tissue which promote hypertrophic scarring. AB - Hypertrophic scars and keloids are characterized by nodules of collagen that originate in granulation tissue arising from full thickness or deep 2 degrees injuries to the skin. Fifty-six granulation tissues of varying ages post-injury were examined morphologically for evidences of how the nodules and, thus, the scar form. New microvessels grow in ascension towards the free surface in a milieu of inflammatory cells and fibroblasts. Collagen deposition increases with time from the base of the wound to the free surface and begins to concentrate between lateral branching of the new microvessels. Computer derived serial reconstructions of hypertrophic scar nodules indicate they are of varying shape and size probably due to fusion of adjacent microvascular collagen masses between lateral branches. This is accomplished by the gradual but persistent degeneration of microvascular endothelia and pericytes. Fifty-six pieces of granulation tissue taken from 5 cases of varying age post-injury were implanted into nude mice. Several proceeded to develop scar and some of those developed nodules. The latter developed only when the zero-time implant contained lateral microvascular branches. Hypertrophic scars and keloids are a product of granulation tissue elements, the most important of which are primed active fibroblasts and excessive microvascular regeneration, including lateral branching, which subsequently degenerates, in part, promoting nodule formation and remodeling. PMID- 2094010 TI - Kidney structure investigations using scanning electron microscopy of corrosion casts--a state of the art review. AB - The corrosion casting technique using acrylic resins in the scanning electron microscope (SEM), was originally developed to investigate renal microvascular structure and is now also successfully used in studies on various other organs. However, in the last two decades nearly 100 papers have been published on the renal vascular anatomy of various taxa of vertebrates or on pathomorphological structures of kidneys, using this technique. Analyzing these works, trends and developments in this field can be summed up as follows: The majority of studies are anatomical works on the vascular system of kidneys from all vertebrate classes. In addition, experimental pathological investigations, mostly done using rodents, and documentation of pathologically altered renal structure form another large part of the publications covered in this review. Perspectives for future research on renal systems using this versatile method may be derived from this survey. PMID- 2094009 TI - Scanning electron microscopy of vascular corrosion casts--technique and applications: updated review. AB - The present paper states very briefly the main steps leading to the technique of scanning electron microscopy (SEM) of vascular corrosion casts. From the terms presently used (injection method, microcorrosion cast, injection replica, vascular corrosion cast, vascular cast) the use of "vascular corrosion cast" for lymphatic and blood vessels is recommended. Specification and pretreatment (kind, volume, dosage of anticoagulants, vasoactive substances and spasmolytica used) of the animals examined are referenced as they are available from the literature. The recommendation is given to pay more attention to these parameters than done so far. The steps necessary for producing reasonable and suitable vascular corrosion casts are critically described. Special attention is paid to the physical and chemical properties of the casting media and their significance for polymerization, shrinkage, casting quality, corrosion resistance, and thermal and spatial stability. Emphasis is also focused on the advantages of cutting the vascular corrosion casts embedded in an ice block by a band saw, a self constructed multi-blade cutting device or a mini wheel-saw placed in the chamber of a cryomicrotome. From the drying methods presently used freeze-drying is stressed because of minimal specimen damage. To render casts conductive in most cases sputter-coating is sufficient. It is recommended to run the SEM with 5-10 kV since the resolution received still reveals all details the casting media presently can replicate. Further the application of scanning electron microscopy of vascular corrosion casts in fully differentiated normal tissue, in pathologic tissue as well as in developing tissues and organs is stated. Lastly possibilities and conditions are discussed under which SEM of vascular corrosion casts can serve to quantify vascular structures in order to make the technique more than pure descriptive. PMID- 2094011 TI - The microvasculature of the guinea pig ureter. A scanning electron microscopic investigation. AB - In 24 albinotic guinea pigs (Cavia porcellus) the gross vasculature and the microvascular architecture of the ureter were studied by light microscopy of tissue blocks and by scanning electron microscopy of vascular casts. The guinea pig ureter is supplied by the renal artery proximally, by the aorta and the internal iliac artery in its mid-segment, and by the uterine and prostatic as well as by the vesical arteries distally. The main arterial trunks run alongside the ureter before they branch to send perforating arterioles to the muscular coat and the mucosal lining. The draining venules are found on both sides of the ureter and form transverse anastomoses. Communications between the arterioles are also located on both sides, but longitudinally arranged. The capillary network of the mucosal lining shows an undulating pattern with tortuous vessels and lies just below the epithelium. The muscular coat and the adventitia have no prominent capillaries of their own. Large arteries are embedded in the adventitia, large veins in the lamina propria. In analogy to human anatomy the vascular arrangement found suggests that, if the ureters are excised in transplant surgery, a lateral incision should be used for the abdominal portion, while the pelvic portion is best approached by a medial incision. PMID- 2094012 TI - Scanning electron microscopy of the celloidin-embedded inner ear sections. AB - The nerve fibers running inside the organ of Corti were studied in cats by scanning electron microscopy (SEM). The fixed temporal bones were decalcified and embedded in celloidin according to the conventional method. Thick serial sections (100-150 microns) were cut parallel to the basilar membrane. After removing the celloidin, the sections were freeze-dried in t-butyl alcohol. Though some outer hair cells had been deformed, the nerve fibers were well preserved for analysis. Some new findings were observed in the present SEM study. The tunnel spiral bundle in a kitten took an atypical course on the floor of Corti's tunnel apart from the previously reported site. In the barely-patent tunnels of Corti in kittens, nerve fibers were stuck together into thick bundles and took different courses compared to those in the mature cochleas. Filiform projections of nerve fibers were climbing around the first row of the outer hair cells in the immature cochlea. These were thought to be growing ends of efferent nerves which would later grow into nerve endings. PMID- 2094014 TI - The morphology of synovial lining of various structures in several species as observed with scanning electron microscopy. AB - Data concerning surface morphology of synovial lining of tendons, tendon sheaths, cruciate ligaments, infra-patellar fat pads and peripatellar synovial ridges in various species (rat, rabbit, dwarf goat, sheep, pig, dog, human) are reported on. Supportive studies with transmission electron microscopy (TEM) and light microscopy were performed. Three principal morphological appearances of the synovium are evident. On structures with a dense fibrous architecture like tendons, tendon sheaths and cruciate ligaments the intimal cells and processes are mostly slender and may tend to orientation in the length-axis of the structure. On the peri- and infrapatellar adipose tissues two principal 'extremes' are seen: one in which the contours of the fat cells are clearly visible with fungoid shaped structures in between them, and one in which the fat cell contours are not recognizable and the intima consists of cauliflower-like cells. Transitional forms exist. Several features observed on tendons and tendon sheaths which have not been reported on before are presented in this paper. A consistent classification of synovium is presented. PMID- 2094013 TI - Fine structure of the inner enamel in human permanent teeth. AB - Using SEM after EDTA etching, the mid-coronal inner enamel of human permanent teeth was classified into three regions of the 1st, 2nd, and 3rd zones. The 1st zone showing a highly negative birefringence was the innermost 10 - 15 microns enamel. This zone consisted of arcade and circular initial prisms, and the succeeding arcade prisms only. These initial prisms arising perpendicularly to the dentine surface resembled pseudoprisms because these prisms showed a somewhat centripetal arrangement of crystallites and indistinct prism boundaries. The succeeding prisms were frequently bent following a faint slit within the prism. The 2nd zone adjacent to the 1st zone measured 20 - 40 microns in thickness. This zone was mainly composed of horseshoe-shaped prisms with EDTA-insoluble prism sheaths in the deep-etched prism boundaries, but the inner-half layer had dotted irregular prisms including circular, double marginal, and spiral shapes with the prism sheaths. Prismless structures were rarely seen in the 2nd zone. The 3rd zone was mainly occupied by horseshoe-shaped prisms without EDTA-insoluble prism sheaths in the deep-etched prism boundaries, although tuft prisms in the 3rd zone contained a large amount of EDTA-insoluble substances in the prisms, interprismatic regions, and the boundaries. PMID- 2094015 TI - [Drug abuse and HIV in the hospital]. PMID- 2094016 TI - [AIDS and drug abuse. Stopping the connection]. PMID- 2094017 TI - [The psychologist. Liaison agent in the patient care team]. PMID- 2094018 TI - [Clinical medicine and social bonds. Social networks in the field of drug abuse (AIDS)]. PMID- 2094019 TI - [HIV infections. Neurologic, psychiatric and psychologic aspects]. PMID- 2094020 TI - [AIDS. Current concerns]. PMID- 2094021 TI - [AIDS and Ekbom's syndrome]. PMID- 2094022 TI - [Reflections and conversations with psychotic seropositives]. PMID- 2094023 TI - [Team conferences. Their place in the health care organization]. PMID- 2094024 TI - [The nurse in home care services: an adventure in methodology, or the experiences of continuing education in a community health center in Rennes]. PMID- 2094025 TI - [AIDS and prevention. The dangers of activism]. PMID- 2094026 TI - [Itinerary of HIV carriers]. PMID- 2094027 TI - [Everything is not psychiatric]. PMID- 2094028 TI - [Hysteria and hypnosis]. PMID- 2094029 TI - [The need for hypnotic therapy]. PMID- 2094030 TI - [Hypnosis and pain]. PMID- 2094031 TI - [Milton H. Erickson in the land of orthophony]. PMID- 2094032 TI - [Round table discussion. Continuing education of psychiatric nurses. Some significant experiences]. PMID- 2094033 TI - [Round table discussion. The nursing service in the production of the psychiatric department organization schema]. PMID- 2094034 TI - [Mentally retarded and psychotic patients. Health policy]. PMID- 2094035 TI - [Workload study. Application of a method in a psychiatric service]. PMID- 2094036 TI - [Present status of hypnosis]. PMID- 2094037 TI - [Brief history of hypnosis]. PMID- 2094038 TI - [A worrisome fever]. PMID- 2094039 TI - [Why La Leche League?]. PMID- 2094040 TI - [Lactation: the first weeks]. PMID- 2094041 TI - [Artificial nipples]. PMID- 2094042 TI - [Myths and realities about breast feeding the premature infant]. PMID- 2094043 TI - [The baby "who will not nurse"]. PMID- 2094044 TI - [Breast feeding after a cesarean]. PMID- 2094045 TI - [Work and the pursuit of breast feeding]. PMID- 2094046 TI - [Why always talk about nutrition?]. PMID- 2094047 TI - [Dietetic milk products for the first year]. PMID- 2094048 TI - [Round table discussion. High-risk pregnancies. Cooperative work between the puericulturists and the midwives]. PMID- 2094049 TI - [Round table discussion. Fertilization in vitro]. PMID- 2094050 TI - [Minor functional digestive disorders in the infant]. PMID- 2094051 TI - [Intolerance to cow milk proteins. Early forms and prevention]. PMID- 2094052 TI - Successes and failures in the treatment of bronchial asthma. AB - In the past decade a spectacular development could be observed in the field of antiasthmatic drugs. Though the new drugs did not produce radical change but they created a wide range of treatment possibilities. This paper is dealing with three, probably most rapidly developing fields of asthma therapy. 1. Immunotherapy. The most important allergens could be isolated in a high purity with up-to-date chemical analitical methods. This affords possibility for a more reliable determination of individual sensitivity and desensitizing treatment. 2. Mediator release blocking drugs. While common antiasthmatic medicaments try to counterbalance the effect of chemical mediators released by antigen-antibody reaction, the former partly block mediator release but also decrease bronchial hyperreactivity characteristic of asthma. 3. Glucocorticosteroids. Recent halogenized steroid preparations did not diminish the risk of severe side effects. Their application is limited in time, they are used mainly for the prevention and treatment of asthmatic crisis. Among aerosolized steroids, preparations considered as optimal have local effect but they are slightly absorbed from the mucous membrane. In spite of the new drugs, medication depending on individual sensitivity, actual complaints and lung function values is essential, the asthmatic needs continuous care based on symptoms, complaints. PMID- 2094053 TI - Use of a new erythromycin product--eryc--in the treatment of the lower respiratory tract infections. AB - Eryc therapy was used in 27 patients admitted with acute exacerbation of chronic obstructive bronchitis, and in 4 patients with pneumonia. Depending on the severity of the condition the dose of the drug was 4 x 500 mg or, in a lower number of cases, 4 x 250 mg. The effectivity of therapy was evaluated on the basis of the changes in the quality of sputum, elimination of facultative pathogens identified from sputum at admittance, clinical symptoms, respiratory function values, blood gas values, and, in case of pneumonia, improvement of chest X-ray finding. Eryc therapy proved to be effective in 78.6% of the cases. Side-effects were observed in 25.8% of the cases but the therapy had to be discontinued because of the severity of unwanted effects only in 3 patients (9.7%). The change of the method of drug administration-intake during meals-did not decrease the frequency of side-effects when compared to Hungarian data. On the basis of our results Eryc therapy was found to be useful for the treatment of the lower respiratory tract, community-acquired infections. PMID- 2094054 TI - The role of a peripheral dopamine-antagonist (Motilium) in improving the tolerance to steroidal and non-steroidal anti-inflammatory agents. AB - Domperidone protective therapy has been applied in 50 patients suffering from locomotor disease, who responded with dyspeptic complaints to the steroidal and non-steroidal antiphlogistic therapies which meant a risk of the activation of an earlier gastro-intestinal disease. The basic therapy could be applied to 80% of patients due to the Motilium protection because of the favourable changes in gastro-intestinal symptoms. Since domperidone is well tolerated by the patients and it does not yield higher risks, it's use is highly recommended as a protective therapy as well. PMID- 2094055 TI - Results of a multilateral study with Anteovin. AB - The development of biphasic oral contraceptives is briefly reported and the theoretical basis and advantages of the biphasic method are discussed. The clinical observations referring to Anteovin which have been published until present are summarized and data of 43 authors are statistically analysed. Target specific examinations on the haemostasis and lipid metabolism influencing effect of Anteovin are mentioned. The therapeutic usefulness of biphasic tablet is analysed, the age-related possibilities, the problems of drug interactions and the dermatological advantages of the product are also discussed. With the present study the author wants to prove that the use of the low-dose multiphasic tablets is at present the most acceptable method of oral contraception. PMID- 2094056 TI - Adjuvant effect of cavinton in the treatment of climacteric symptoms. AB - A comparative study has been performed in 40 climacteric, postmenopausal women. In the course of the examinations the results of two therapeutic methods were compared: hormone substitution therapy and combined hormone substitution and Cavinton adjuvant therapy. The improvement in the climacteric symptoms was measured by Kupperman's index and the results were statistically analysed. According to the results Cavinton significantly improves the changes in the symptoms to be obtained with oestrogen substitution. On the basis of the observations the author recommends the combination therapy. Cavinton did not cause side-effects which would have influenced the long-term use of the drug. PMID- 2094057 TI - Observations with trimethoprim tablet used in urinary tract infections. AB - Trimethoprim monotherapy was applied in 50 cases. Recovery was obtained in 18 patients (36%), improvement in 15 patients (30%), and in 17 cases (34%) no change was observed in response to the therapy. Trimethoprim therapy may be successfully used in acute and chronic cystitis and urethritis-especially in E. coli infections. The therapy is significantly less effective in urinary tract infections caused by other Gram-negative and Gram-positive micro-organisms. In the course of drug therapy only a few side-effects were observed. PMID- 2094058 TI - Improvement of lipid metabolism with fenofibrate in gynaecological borderline cases. AB - The effect of fenofibrate (Lipanthyl) on the more important lipid levels has been examined in 58 female patients. The other diseases of the women have been treated as well. The drug moderated cholesterol level very successfully. In response to the drug the serum cholesterol, serum triglyceride and LDL-cholesterol values decreased and the HDL-cholesterol level increased. The long-term application of the drug was well tolerated by the women. The introduction of fenofibrate is recommended in particular in the treatment of those internal-gynaecological diseases and postmenopause in which the normal lipid levels may facilitate to reach the final goal of therapy. PMID- 2094060 TI - Lajos Thanhoffer Jr., the Belgian Congo's Hungarian physician. PMID- 2094059 TI - The relationship between vascular headaches and low-dose oral contraceptives. AB - The relationship between migraineous headaches and the use of low-dose oral contraceptives, the monophasic Rigevidon and the biphasic Anteovin, has been examined. In the examined cases Anteovin of higher oestrogen content provoked more vascular cephalalgias than Rigevidon with it's lower oestrogen content. In one part of the cases both pills even had therapeutic effects. According to the opinion of the author classical migraine means a relative contra-indication of hormonal contraception and is a serious adverse effect requiring the discontinuance of oral contraception. The headaches develop during the adaptational period of oral contraception and the migraineous attacks occur in the premenstrual period or at the beginning of menstruation which refer to an oestrogen withdrawal character. It may be supposed that vasoconstriction of certain extent, which has existed during the use of the pills, changes over to relative vasodilatation in this period and the extent of the changes is dependent on the oestreogen content of the tablets. PMID- 2094061 TI - Factors involved in trace element metabolic abnormalities in hemodialysis patients. AB - Hair samples taken from a patient group comprising 28 long-term hemodialysis patients (14 males and 14 females) and a control group comprising the same number of normal humans with the same age, sex, residence region, working region and sampling timing as the patient group were analyzed for 22 elements. These subjects were all free of exposure to any trace element. The results are as follows: 1) The patient group had no difference from the control group in hair Na, K, Ca, P or Mg level, variance or correlation coefficient between two elements. 2) The patient group had significantly higher values of hair Se, Sn, Mo and Cr levels and significantly lower values of hair Fe, Ni, Co, Pb and Cd levels. 3) In the patient group, variances of Se, Sn, Mo, Cr and Sr levels were significantly lower. 4) A significant correlation was found in P-Mo. Mg-Sr, Zn Fe, Li-Sr, Mo-Sb and Cr-Co in both groups, with a significant difference in correlation coefficient between the two groups. 5) The following four factors, causative of trace element level changes in the patient group, were derived by factor analysis: Factor 1, involved in Ca metabolism, Factor 2, involved in dietary therapy, Factor 3, involved in water metabolism, and Factor 4, involved in an unknown pathologic status based on both chronic renal failure and hemodialysis. 6) Factor analysis revealed abnormal behavior of Sr, Li, Al and V, all of with showed no level changes in the patient group. PMID- 2094062 TI - Intrahepatic cholestasis with gallstones in two siblings: a new hepatobiliary syndrome in association with anomalous arrangement of pancreaticobiliary ducts. AB - Two siblings (a 2-year-old female and 11-month-old male) with similar onset of obstructive jaundice and clinical manifestations from early infancy are described. The jaundice fluctuated but never completely disappeared. Abnormal amounts of cholate, chenodeoxycholate and ursodeoxycholate were found in serum bile acid fractions. Pruritus, hyperbilirubinemia of predominantly the conjugated fraction and bilirubinuria were increased by repeated respiratory infections. Ultrasonography showed several highly echogenic shadows in the gallbladder in both cases, and gallstones were found at surgery. Operative cholangiography showed an anomalous arrangement of pancreaticobiliary ductal system in both cases. The pedigree showed five relatives (including the father) on the paternal side had liver disease, and an autosomal recessive inheritance was suggested. The association of familial intrahepatic cholestasis with a large amount of serum bile acids (which seem to be due to abnormal bile acid metabolism), cholelithiasis and anomalous arrangement of the pancreaticobiliary ductal system is proposed as a new hepatobiliary syndrome. PMID- 2094063 TI - Effect of magnesium sulfate on ventricular refractoriness and its efficacy for torsade de pointes. AB - The effect of magnesium sulfate on ventricular refractoriness and its efficacy for torsade de pointes (TdP) were studied in nineteen dogs. After the administration of quinidine sulfate (30 mg/kg), TdP was induced by ventricular pacing in ten of 19 dogs (52.6%), polymorphic ventricular tachycardia in seven (36.8%), ventricular fibrillation in two (10.5%). Quinidine sulfate caused significant increases in QTc interval, ventricular effective refractory period (ERP) and dispersion of ERP(dERP), and decrease in ERP/QT. Magnesium sulfate significantly increased ERP (p less than 0.01), but it did not change QT interval, resulting in significant increasing of ERP/QT (0.41 +/- 0.05 to 0.61 +/ 0.05, p less than 0.01). It decreased dERP but not significantly. Magnesium sulfate prevented the induction of TdP in eight of 10 dogs (80.0%) (30 mg/kg in four and 60 mg/kg in four). In conclusion, magnesium sulfate has value as first aid therapy for drug-induced TdP. If patients have ischemic heart disease or hypertension, we recommend infusion of magnesium for the initial therapy of TdP. PMID- 2094064 TI - Effects of 1 alpha-hydroxyvitamin D3 on N-methyl-N-nitrosourea-induced colonic tumorigenesis, and on fecal bile acid profiles with respect to soluble and precipitated phases in rats. AB - Vitamin D3 inhibited the promotion by exogenous promoters in experimental colonic tumorigenesis. To give more insight into this phenomenon, the effect of 1 alpha hydroxyvitamin D3 (1 alpha(OH)D3) on N-methyl-N-nitrosourea (MNU)-induced colonic tumorigenesis was studied in rats without exogenous promoters. Fecal bile acids were analyzed to examine as to whether 1 alpha(OH)D3 increased the concentration of soluble bile acids. Eighty-seven female F344 rats received 2 mg of MNU intrarectally 5 times in 2 weeks, and were divided into 3 groups. One group (n = 29) was left without any treatment. Two groups (each, n = 29) were given 0.2 ml of medium chain triglyceride (MCT) or MCT containing 0.04 microgram of 1 alpha(OH)D3 through an intragastric route thrice weekly for 38 weeks. At autopsy, numbers of rats with colonic tumor were 9 (31%), 10 (34%) and 10 (34%) in the group receiving MNU alone, MNU + MCT and MNU + 1 alpha(OH)D3, respectively (chi 2 = 0.103, P less than 0.95). Fecal bile acid profiles showed no appreciable difference among these groups, nor was observed any increase of soluble bile acids in the MNU + 1 alpha(OH)D3 group. These results indicated that the administration of 1 alpha(OH)D3 did not affect colonic tumorigenesis under the condition where exogenous promoters were not applied, and that 1 alpha(OH)D3 did not seem to interfere the formation of bile acid calcium salts in animals on a regular diet. PMID- 2094065 TI - Comparison between a glucose-fructose-xylitol solution and a sole glucose solution for surgical patients with glucose tolerance impairment. AB - The metabolic response to the postoperative delivery of a sole glucose solution or a glucose-fructose-xylitol solution, and their effects upon carbohydrate metabolism, in patients with glucose tolerance impairment, were evaluated. Twenty four patients who showed an abnormal 75g-OGTT or were noninsulin-dependent diabetics were divided in two groups. The GFX-B group (n = 11) received a 10.5% solution, containing glucose, fructose and xylitol at 4:2:1 ratio, and the PHY-3 group (n = 13) received a 10% glucose solution, both, continuously infused for 3 days postoperatively. The infusion of PHY-3 tended to produce a higher increase in blood glucose than the infusion of GFX-B, that was significantly different on the 3POD (P less than 0.05). The increase in IRI and CPR was also significantly greater in PHY-3 group than in GFX-B group on the 3POD (P less than 0.05). We concluded that it was not only the slight lower glucose load of the GFX-B solution, but also, the different infused carbohydrate substrate which had influenced the magnitude of insulin secretion and the blood glucose level. Then, its use in glucose intolerant patients may be of some benefit to partially minimize the postoperative hyperglycemic response. PMID- 2094066 TI - [Brief definition of medical ethical concepts. 3]. PMID- 2094067 TI - [First somatic human gene therapy in the USA approved]. AB - The clinical protocol to treat infants with severe combined immuno deficiency due to adenosine deaminase (ADA) deficiency by means of gene thereapy has been approved recently. The Human Gene Therapy Subcommittee and the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH) concluded the review on July 30th and opened the door for the first federally approved somatic Human Gene Therapy. PMID- 2094068 TI - [Abortion and the experience for the physician who performs it]. PMID- 2094069 TI - [Profile of Carita Klingstedt. Interview by Pelle Olsson]. PMID- 2094070 TI - [Study shows: shortage of personnel--need for education. Interview by Jan Thomasson]. PMID- 2094071 TI - [The administrator's job is a double homecoming for Gunnel. Interview by Elisabet Forslind]. PMID- 2094073 TI - [Focus on working environment. Why do nurses take their own life?]. PMID- 2094072 TI - [Focus on working environment. Nursing--"work exposed to various health risks"]. PMID- 2094074 TI - [Less nursing care in occupational health services!]. PMID- 2094076 TI - [Hierarchy and work environment]. PMID- 2094075 TI - [Employment in a practitioners' service--it is hard to know who is qualified]. PMID- 2094077 TI - [The overall responsibility is ours. Interview by Jan Thomasson]. PMID- 2094078 TI - [Those trained abroad can become SHSTF members]. PMID- 2094079 TI - [TCO's Summer university (Organization for Salaried Employees): women's struggle against "obsolescence"]. PMID- 2094080 TI - [Annette bicycles one day a week during working time]. PMID- 2094081 TI - [Focus on work environment. The environment in laboratories could be better. High staff turnover opened eyes of hospital management]. PMID- 2094082 TI - [Effective Swedish nursing care is bursting its frame]. PMID- 2094083 TI - [Profile of Bengt Dahlquist. Interview by Pelle Olsson]. PMID- 2094085 TI - [Sports for play]. PMID- 2094084 TI - [Prioritizing in health care doesn't mean acceptance]. PMID- 2094086 TI - [Henry trains in day care. Interview by Carina Roxstrom]. PMID- 2094088 TI - [SHSTF (Swedish Federation of Health Officers) has long wanted increased independence. Interview by Jan Thomasson]. PMID- 2094087 TI - [KTK and TCO-S are disappearing--SHSTF will negotiate alone]. PMID- 2094089 TI - [Law proposal on alternative medicine gets both blame and praise]. PMID- 2094090 TI - [An example with children in Rumania. Nothing in nursing care should escape personal responsibility]. PMID- 2094091 TI - [Voluntary cooperation needs a new negotiation model]. PMID- 2094092 TI - [Focus on work environment. Improve efficiency, renew says Sahlgrensk and runs over the staff]. PMID- 2094093 TI - [The alkaline phosphatase activity of the blood serum as a factor reflecting the chronic inflammatory process in the skin in generalized forms of psoriasis, neurodermatitis, eczema and trophic ulcers]. AB - Blood serum alkaline phosphatase (AP) level was found elevated in the patients suffering from eczema, neurodermatitis, eczema with large skin sites involved, and in those with trophic ulcers of various origins, as against normal subjects and reference patients with sarcoidosis and Kaposi's sarcoma. Elevated level of the enzyme activity is directly related to exacerbation stage and size of the skin site involved; this level reduced after therapy and this reduction was associated with clinical improvement. No concomitant visceral abnormalities (calculous cholecystitis, liver cirrhosis, or malignant tumors) were detected in the examinees, that might influence the blood serum AP activity. PMID- 2094094 TI - [Changes in the morphological structure of the skin and internal organs of guinea pigs after multiple epicutaneous exposures to furfural, a distillate of D-11 mineral oil and their combinations]. AB - Experimental multiple epicutaneous exposure of guinea pigs to furfural and D-11 mineral oil distillate and their combinations in various concentrations has resulted in structural changes of the skin and viscera. These changes were dose dependent. Combined exposure to both agents resulted in more grave disorders than isolated exposures in the same doses. PMID- 2094096 TI - [The problem of the terminology of "diffuse neurodermatitis--atopic dermatitis" in the work of the expert physician]. AB - The problem in terminology, regarding diffuse neurodermatitis or atopic dermatitis, is discussed from a viewpoint of an expert physician evaluating the health status of certain patients populations. The author advocates A. A. Kalamkarian and V. A. Samsonov's view point, for it permits expert evaluation of the subjects' health status from a universal clinical and methodological standpoint. PMID- 2094095 TI - [The effect of nizoral and tinidazole on neutrophilic phagocytic activity in patients with rubromycosis and candidiasis]. AB - Nisoral and tinidasole effects on Trichophyton rubrum and Candida albicans ability to be destroyed by neutrophils were under study, as were the characteristics of neutrophil phagocytic activity in patients with various forms of trichophytosis and candidiasis over the course of nisoral or tinidasole therapy or combined therapy with both the drugs. Tinidasole and more so nisoral were found to enhance neutrophilic fungicidal activity towards Tr. rubrum and C. albicans. Combined therapy with nisoral and tinidasole distinctly augmented the counts of Ns-RFC and Nc-RFC and increased the values of the phagocytic index and the phagocytic number. Combined administration of the drugs was conducive to elevation of the neutrophilic ability to destroy the fundal elements. PMID- 2094097 TI - [The effect of ultrasonic oscillations and amphotericin B on the ultrastructure of yeast-like fungi in the genus Candida]. AB - C. albicans cellular structure was examined electron microscopically over the course of amphotericin B treatment. The efficacy of amphotericin B administration via phonophoresis is demonstrated. PMID- 2094098 TI - [A lymphotropic method of therapy for patients with fresh forms of syphilis (clinical and experimental research)]. AB - Experimental study of benzylpenicillin procain salt kinetics in lymphotropic and intramuscular administration of 600,000 U has revealed a more intensive saturation of the lymph system and a longer persistence of high concentrations of the drug in the blood serum, organs and tissues of the body after lymphotropic administration, as against intramuscular one. Comparison of the efficacies of 16 day courses of therapy of patients with fresh syphilis with benzylpenicillin procain salt administered lymphotropically (once daily, 600,000 U) or intramuscularly (twice daily, the same dose) has shown the advantages of the former method as regards the therapeutic, pharmacokinetic, and economic aspects. PMID- 2094099 TI - [Vipsogal in the therapy of psoriasis]. AB - A new external drug, vipsogal, manufactured by Galenika, Yugoslavia, was used in therapy of 205 patients suffering from psoriasis. The drug proved to be fairly effective. The authors recommend vipsogal to be included in the complex of drugs used in therapy of psoriasis. PMID- 2094100 TI - [The use of the enterosorbent polifepan in the combined treatment of patients with dermatoses]. AB - Polyfepan, an enterosorbent, was used in the treatment of 96 dermatologic patients. The treatment proved to be effective in those with toxicoderma, secondary xanthomatosis, porphyria cutanea tarda, skin itching, and urticaria, particularly in the cases when toxic exposures and gastrointestinal conditions contributed to the disease pathogenesis. Polyfepan enterosorption is harmless, well-tolerated, and simple. PMID- 2094101 TI - [Autoantibodies to 5 types of collagen in patients with circumscribed scleroderma]. AB - Elevated levels of autoantibodies to types I-V collagens were detected in local scleroderma patients. In 75 percent of cases the levels of autoantibodies to types I and III collagens were elevated, in 30 percent to type II collagens, in 25 percent to type IV collagens, and in 20 percent to type V collagens. Anticollagen autoantibody levels did not differ from the normal values in the patients with a prolonged (for more than a year) remission. A reduction of these antibody levels almost to the normal values was achieved in 10-12 months after tigason therapy during a prolonged clinical remission. The ratio between autoantibodies to types I and II collagens was found to be a constant both in the donors and patients with local scleroderma. PMID- 2094102 TI - [Tertiary active syphilis in a patient after a third infection]. AB - A patient developing tertiary active syphilis after the third infection is described. A swift development of the condition after the infection is noteworthy. PMID- 2094103 TI - [The diagnosis of gardnerellosis and other nonsporulating anaerobic infection of the urogenital organs]. PMID- 2094104 TI - [The use of fresh capillary blood in immunoenzyme analysis for syphilis]. PMID- 2094105 TI - [The ultrastructural changes in the nerve fibers of the skin in psoriasis]. AB - Electron microscopic examination of the upper layers of the derma in skin biopsy specimens from 20 patients with psoriasis, collected both in foci of lesions and those of apparently intact skin, has revealed that changes in amyelinic nerve fibers are more marked in foci of involvement. Here they may be partly explained by inflammatory processes; but since the nerve fibers are also significantly changed in apparently intact skin, we may suppose that these changes are due to other factors as well. PMID- 2094106 TI - [Electromyography and diabetes. Review of 106 records]. PMID- 2094107 TI - [The value of electromyographic studies of the external anal sphincter]. PMID- 2094108 TI - [Spasmophilia]. PMID- 2094109 TI - [The effect of hot baths on the muscular properties of healthy and of spastic subjects]. PMID- 2094110 TI - [Static and dynamic examination of the knee]. PMID- 2094111 TI - [Post-traumatic synovitis at the level of the knee]. PMID- 2094112 TI - [Current arthroscopic techniques for suturing of the meniscus]. PMID- 2094113 TI - Study on the effect of etofenamate 10% cream in comparison with an oral NSAID in strains and sprains due to sports injuries. AB - In this 60 patient study of sports traumatology due to football injuries, etofenamate gel proved equally effective as oral naproxen on the overall pain scores (65% none to mild pain for etofenamate versus 86% for naproxen; p greater than 0.05). The global clinical impression results have been rated as good or excellent in 44% in the naproxen group versus 50% in the etofenamate group. The incidence of side effects in the etofenamate group (3%) was lower than in the naproxen group (20%). This study demonstrates that etofenamate gel has equal efficacy as oral NSAIDS but a better side effect profile in sport injuries in football players. PMID- 2094114 TI - [Focus on a cervico-arthritic myelopathy: presentation of a clinical case]. PMID- 2094115 TI - [Diagnosis of knee pathology using magnetic resonance imaging]. PMID- 2094116 TI - Determination of the strain response of sheep femur, based on quasistatic walking experiments. AB - The creep strain of fresh femoral sheep bones was measured in the time interval between 10(-2) to 10(+3) sec, when the bones were under compression load of full body weight. The stress developed during walking in the femur was expressed by a step function. A rheological model with three parameters was used to calculate the strain response. The mean features of the calculated strain response of the femur during walking, were the transient phenomena in the beginning of walking and the permanent strain in the steady state. The possible biological and clinical perspectives of this behaviour of the femur are discussed. PMID- 2094117 TI - Genome instability as a consequence of DNA-repair and immune system abnormalities. AB - The cellular level analysis of 720 clinically persons with cytogenetic abnormalities has been performed in this study. Of them 25% showed an increased number of cells with cytogenetic abnormalities. Repeated examination of these patients allowed to "eliminate" sporadic cases of genome instability from the given group. The remaining, 30% of cases, had reliable decrease in excision repair and significant changes in immunoreactivity. At the same time a decrease of activity of DNA-repair synthesis was noticed in donors with a higher number of cells with cytogenetic aberrations. PMID- 2094118 TI - Repair studies on methylated DNA of CHO cells. AB - DNA methylation pattern was investigated on Chinese hamster ovary (CHO) cells after treatment with N-(14C)-methyl-N-nitrosourea (14C-MNU). The main target was the N-7 position of guanine, exceeding the methylation in the O6 position of guanine by a factor of 8 and that in the N-3 position of guanine and adenine by a factor of 20. No DNA repair could be observed within 2 hours after methylation. Pretreatment of cells with gamma irradiation (7 rad) before application of MNU induced repair of N-7-methylguanine. This methylation product was decreased to about 50% within two hours, whereas the repair of the other methylated bases was not influenced. The analysis was carried out by high performance liquid chromatography after acid hydrolysis of isolated DNA. 14C-methylated products were determined by liquid scintillation counting. PMID- 2094119 TI - Comparison of cytogenetic tests for monitoring overexposures from ionizing radiation. AB - The frequencies of chromosome aberrations induced by ionizing radiations were studied for use in assessment of doses in radiation accidents. The dose-effect relationships of formations of dicentric and acentric aberrations are compared with that of micronuclei detected in cultured human lymphocytes. The data suggest the applicability of micronucleus test as "biological dosimeter" with a similar sensitivity like the widely used dicentric analysis. PMID- 2094120 TI - SCEs and chromosome aberrations in mammalian cells in vitro treated with quercetin. PMID- 2094121 TI - Effect of low-dose radiation on repair of DNA and chromosome damage. AB - In this report results of studies on the effect of different doses of low LET (linear energy transfer) radiations on the unscheduled DNA synthesis (UDS) and DNA polymerase activity as well as the induction of adaptive response in bone marrow cells (BMC) by low dose radiation were presented. It was found that whole body irradiation (WBI) with X-ray doses above 0.5 Gy caused a dose-dependent depression of both UD5 and DNA polymerase activity, while low dose radiation below 250 mGy could stimulate the DNA repair synthesis and the enzyme activity. WBI of mice with low doses of X-rays in the range of 2-100 mGy at a dose rate of 57.3 mGy per minute induced an adaptive response in the BMC expressed as a reduction of chromosome aberrations following a second exposure to a larger dose (0.65 mGy). It was demonstrated that the magnitude of the adaptive response seemed to be inversely related to the induction dose. The possibility of induction of adaptive response in GO phase of the cell cycle and the possibility of a second induction of the adaptive response were discussed. PMID- 2094122 TI - Cytological analysis of radiation-induced DNA amplification in C57BL/6 mice. AB - Inbred mouse strain C57BL/6 pre-treated with or without the drug with suspected anticancer activity, DADH (N, N'-Diacetyl-1, 6-Diaminohexane) by daily feeding for five consecutive days to a total dose of 1 mmol of the drug in aqueous solution, were exposed to an acute dose of 1 Gy gamma radiation. Appropriate controls without radiation were maintained both for water and DADH-fed groups of animals. At 18 and 36 h post-irradiation the animals from all four groups (designated as A to D with each group having six animals) were sacrificed and their bone marrows were cultured for chromosomal analysis. Special emphasis was put on the estimation of the frequency of occurrence of extra chromosomal elements, such as minutes, single or double (DMS) as a possible assay for radiation-induced DNA amplification (presumably representing the proliferation specified genes(?) causing initiation of a very early tumourigenesis event). Gamma irradiation alone yielded the highest frequency of such minute chromosomal structures concerned (DMS), which was significantly reduced by DADH pre treatment. The preliminary cytological data are discussed in the light of current information on DNA amplification pertaining to carcinogenic induction. PMID- 2094123 TI - The Chernobyl fallout in Salzburg/Austria and its effect on blood chromosomes. AB - The radioactive fallout of the Chernobyl accident caused an increase in radiation dose of 20 to 110 per cent over the normal environmental burden to the inhabitans of Salzburg City in Austria (in a distance of about 1300 km from the accident). The structural chromosome aberration in the lymphocytes of the peripheral blood of 15 test-persons have been investigated one year after the accident. From two of these we know also the aberration frequencies before the accident which were significantly lower. The results from all test persons were pooled according to their Cs137 and Cs134 content, measured by whole body counter. Their mean additional blood doses from the incorporated caesium plus the external fallout radiation were 0.23, 0.36 and 0.55 mGy/yr. The aberration frequencies increased with dose. The slope of the best straight-line through the points was 2.0 +/- 0.7 total chromosome type aberrations in 100 metaphases per mGy/yr. This result fits in well with former investigations of persons with individually calculated radiation burden from the environment. The sharp increase with dose at this low level is not compatible with values extrapolated from high doses. The usual dose assessment based on chromosome aberrations extrapolated from high to low doses is therefore not possible in the range considered in this investigation. PMID- 2094124 TI - Sister chromatid exchanges (SCEs) in lymphocytes of persons working at Shlobin (USSR), 150 km north of Chernobyl. AB - Workers at a building plot in Shlobin (USSR), 150 km north of Chernobyl, were examined for the occurrence of spontaneous and mitomycin C induced SCEs in peripheral lymphocytes. Personnel being present during and after the Chernobyl accident exhibited a decreased number of inducible SCEs compared with test persons starting work at Shlobin by 1st of June, 1986. Since effective dose equivalents were rather low (about 2 m Sv till the end of August 1986), induced SCEs proved to be a very sensitive test for the demonstration of low dose exposure. PMID- 2094125 TI - Continuous induction of unscheduled DNA synthesis by gamma irradiation. AB - The induction of DNA-synthesis in non-S-phase cells is a very sensitive measure of a preceding damage of DNA. Usually, in an in vivo-in vitro test (treatment of an animal, incorporation of H3-thymidine in a cell suspension) the damaging of DNA takes place hours to days before the evaluation. In this case, the time course of the UDS-induction after a single dose of 1 Gy gamma irradiation was observed over a long period of time (21 months). C57 black mice served as test animals. In an age of about 80 days they were irradiated and the induction of unscheduled DNA synthesis was measured at ten time intervals during the whole life-span of the animals. Although the repair in this gamma radiation damage in DNA is a very quick process--with centrifugation in alkaline sucrose a half-life of some minutes is found--an induction of unscheduled DNA synthesis could be seen at the irradiated animals until the end of their life (640 days). The reason for this could be permanent disorders in cellular regulation caused by the gamma irradiation. PMID- 2094126 TI - DNA repair and human pathology. AB - Disorders in the DNA repair in the human lymphocytes isolated from patients with Marfan's syndrome, homocystinuria, schizophrenia, and gout have been found. In this investigation criteria used estimating the DNA repair were the following: host cell reactivation (vaccinia virus reactivation) and its mutagenesis, DNA repair synthesis, resynthesis of DNA breakages. Lymphoblastoid interferon was used as a modulator of DNA repair activity. Pretreatment of normal human cells with interferon stimulated all steps of DNA repair. In human cells with disorders, interferon stimulated DNA repair (XP) in some cases but failed in others. PMID- 2094127 TI - The general mechanism of chromosomal mutagenesis: basic and applied aspects. AB - Based on the analysis of literature and the findings of the present work, it is assumed that there are two main mechanisms of formation of structural chromosome mutations in eukaryotic cells: 1) homologous recombinations, resulting in the formation of all kinds of chromosome exchanges; 2) the process of telomere formation, resulting in the generation of true deletions. Some chromosome breaks registered in the first K-mitosis of cells after exposure to mutagens reflect temporary disturbance of chromatin condensation. These aberrations can be repaired in the next nuclear cycle. Data are presented that argue in favour of the existence of a minor fraction of DNA sequences that serve as the molecular basis of specific targets of chromosome mutagenesis. These sequences can play an essential role in the normal structural and functional organization of the nucleus. PMID- 2094128 TI - Differentiation control in cell cycle and development based on the alterations of higher-order chromatin structure. Theory and applications to radiation and chemical action. AB - A theoretical model of genes switching during development and cell cycle is proposed. The model is based on the assumption concerning the connection between differentiation state and distribution of chromatin domains in the nucleus. Radiation and chemicals action as supposed in the model is realized not at the DNA secondary structure level, but by the damage of chromatin supramolecular states spectrum and transition probabilities between states. PMID- 2094129 TI - Effect of epidermal growth factor (EGF) and insulin on the kinetics of radiation induced DNA lesions repair. AB - To study the effect of both epidermal growth factor and insulin in terms of possible regulation of the repair process in cells, the time-course dependence of SSB and DSB repair have been investigated either in the presence of EGF (10 micrograms/ml) and insulin (1 microgram/ml) or without these factors in the medium (either supplemented with 10% serum or without serum) on Swiss 3T6 cells, exposed to ionizing radiation at a dose of 5-10 Gy using methods of neutral and alkaline elution as well as centrifugation on alkaline sucrose gradients. The absence of serum in the incubation medium during 18 to 24 hours before irradiation resulted in a sharp decrease in the rate of the repair of both single strand break (SSB) and double-strand break (DSB). When cells were exposed to EGF and insulin immediately before irradiation the processes were restored to a significant extent. Data suggest that in the absence of other serum components, EGF and with insulin, are involved in the regulation of the repair of radiation induced DNA lesions. PMID- 2094130 TI - Repair of radiation induced DNA damages in unicellular green algae. AB - Two cell repair systems--photoreactivation and repair of single-strand DNA breaks have been studied using unicellular green algae as a test-system. Effects of the genotype and the intensity of pico/second UV-laser irradiation on the degree of the photoreactivation have been investigated. It has been shown that the lower intensity (I = 8.10(6) W/cm2) effects less the inactivation of living cells comparing with I = 30.10(6) W/cm2, regardless of the genotype. The clearly expressed higher potentials of strains LARG-1 and 260 to produce and repair alterations of the cyclobutane-pyrimidine dimers type have been established. An analysis of DNA degradation during gamma rays irradiation and after incubation has been carried out for investigation the relationship between strains radioresistance and repair of single-strand break. It has been shown that high efficiency of the repair system is characteristic of the resistant strain obtained from chronically irradiated population. PMID- 2094131 TI - The use of metabolic inhibitors in the analysis of eukaryotic DNA repair. AB - By now, it is well established that DNA repair can be inhibited. It is not surprising that many inhibitors of replicative DNA synthesis also effect repair, since the two processes involve similar biochemical steps carried out by analogous if not identical enzymes. No specific inhibitors of repair are known, and care must be taken when interpreting results to be sure that observed effects of inhibitors unambiguously relate to repair. With this caveat, it remains true that inhibitors are valuable tools for the dissection of repair pathways in the classic biochemical fashion, looking for accumulation of intermediates at a point before the enzymic step that is blocked. PMID- 2094132 TI - Selective DNA repair in active genes. AB - My colleagues and I have discovered intragenomic heterogeneity in DNA repair in mammalian cells. Consequences of unrepaired DNA damage depend upon the precise location of the damage with respect to relevant genes. It is therefore important to understand rules governing accessibility of specific DNA sequences in chromatin to damage and repair. The efficiency of removal of pyrimidine dimers has been mapped in the active dihydrofolate reductase (DHFR) gene in Chinese hamster ovary (CHO) cells. Repair within the gene was shown to be much more efficient than that in silent downstream sequences or in the genome overall. Preferential repair of active and essential genes such as DHFR may account for the fact that rodent cells are as UV-resistant as human cells in spite of their much lower overall repair efficiencies. In repair proficient human cells the rate of repair in the DHFR gene is greater than that in the overall genome or in non transcribed alpha DNA sequences. The efficiency of removal of pyrimidine dimers is much higher in the transcribed than the non-transcribed DNA strands of the DHFR gene in both CHO and human cells. An excision-repair complex may be directly coupled to the transcription machinery to ensure early removal of transcription blocking lesions in active genes. Sequences in the active c-abl protooncogene are repaired much more efficiently than are sequences containing the inactive c-mos protooncogene in Swiss mouse 3T3 cells. Tissue specific and cell specific differences in the coordinate regulation of protooncogene expression and DNA repair may account for corresponding differences in the carcinogenic response. Efficient replicative bypass of persisting psoralen monoadducts, but not interstrand crosslinks, was demonstrated in the human DHFR gene. It is likely that most bulky lesions in mammalina DNA, other than crosslinks, do not pose insurmountable problems for replication in vivo, but they must be removed from essential transcribed sequences to maintain cellular viability. PMID- 2094133 TI - The poly-ADP-ribosylation system of higher eukaryotes: a protein shuttle mechanism in chromatin? AB - The role of poly ADP-ribosylation in DNA excision repair was studied in experimental models of various complexities. In intact cells in vivo, the unfolding of chromatin during DNA excision repair apparently requires the presence of a functional poly-ADP-ribosylation system. In vitro studies involving a reconstituted poly-ADP-ribosylation system show that the enzyme poly(ADP ribose)polymerase has the capacity to shuttle core histones on a core DNA fragment of 146 bp. Under these conditions, the polymerase operates in a strictly processive mode. Furthermore, the polymerase adapts to different shuttling targets by producing very distinct polymer patterns. We conclude that the eukaryotic poly-ADP-ribosylation system has the capacity to regulate DNA-protein interactions and this may be an essential part of the unfolding mechanism of chromatin during excision repair in vivo. PMID- 2094134 TI - Poly(ADP-ribose)-synthesis and excision repair in light sensitive skin disorders. AB - Several data suggest a relationship of poly(ADP-ribose) (PAR) synthesis to DNA repair and the influence of some trace elements on the semiconservative and unscheduled DNA synthesis (UDS). Previously we found certain alterations in the UV-light induced UDS and in the contents of trace elements in the lymphocytes of patients with light sensitive skin disorders. In the recent study in polymorphic light eruption, cutaneous porphyrias and xeroderma pigmentosum the PAR synthesis and zinc, copper and manganese contents in the chromatin of the lymphocytes (measured by neutron activation analysis) were investigated. UV induced PAR synthesis was generally lower in the cells of polymorphic light eruption and especially in xeroderma pigmentosum with a reduced repair capacity whereas in cutaneous porphyrias no difference was observed. Some correlations occurred between the contents of trace elements studied and UDS as well in each group tested. It seems that PAR investigations throw new light upon our understanding of the pathomechanism of photodermatoses. PMID- 2094135 TI - Modern treatment of dysmenorrhea. PMID- 2094136 TI - Operative hysteroscopy in the treatment of intrauterine disorders. PMID- 2094137 TI - Perinatal mortality in a Swedish county 1980-1984. Mortality pattern and its amenability. AB - A retrospective, community based study on perinatal mortality was performed in a sparsely populated county with decentralized antenatal and maternity care. Neither level of care nor domicile showed any relation to perinatal mortality. A substantial underreporting of perinatal deaths was revealed. Death causes were classified according to the modified Aberdeen classification. One child per 2,000 births is stillborn due to asphyxia during delivery. Maternal age outside the optimal age range for reproduction was a significant risk factor. A suboptimal standard of care was identified in 33% of the perinatal deaths. PMID- 2094138 TI - Risk determinants of perinatal mortality in a Swedish county, 1980-1984. AB - A retrospective case-referent study was performed to analyse risk factors of perinatal mortality. Overweight defined by body mass index, smoking greater than 10 cigs/day, infertility, earlier birth weight, earlier perinatal death were significant risk determinants of the obstetric history. Overweight and smoking, measured by the etiologic fractions, had the greatest impact on perinatal mortality. Significant risk factors of the present pregnancy were low weight gain, pre-eclampsia, cervical incompetence, and late hemorrhage. Intra-uterine growth retardation had the highest etiologic fraction. High risk assessment at the first antenatal visit had a sensitivity of 45%, increasing to 72% when adding supervening pregnancy complications. Although the positive predictive value of high-risk classification was very low, 2/3 of the perinatal deaths occurred among high-risk cases. PMID- 2094139 TI - One-stage ultrasound screening in pregnancy. An evaluation. AB - A one-stage ultrasound screening program was evaluated, using a pregnancy/perinatal database containing information from 2766 pregnancies and deliveries. Among women who did not have a second-trimester ultrasound examination, labor was induced for presumed post-term pregnancy in 4.0% versus 1.6% of pregnancies in the screening group (p = 0.007). In the group with second trimester ultrasound scanning other than screening, the frequency was 3.2%. Of women with spontaneous labor or who were induced for presumed post-term pregnancy, 3.8% in a screening group and 8.0% in a group with other second trimester ultrasound examination were post-term according to BPD measurements (p = 0.0003). In the screening group, 6.2% of liveborn singletons were small for gestational age (less than the 10th percentile) compared with 8.5% in the non screening group (p less than 0.05). A subset of 365 screened women with optimal menstrual history had spontaneous labor or were induced for presumed post-term pregnancy. According to menstrual history and ultrasound examination, 7.4% and 3.8% of these were post-term, respectively (p = 0.04). It is concluded that the main value of screening lies in a more accurate dating of pregnancy, even when menstrual history is optimal, with a lower incidence of induced labor for believed post-term pregnancies. In addition, there may be an improvement in the obstetric management of pregnancy, reflected in our study as a lower incidence of small for gestational age infants. PMID- 2094140 TI - Idiopathic recurrent spontaneous abortion. Evidence of a familial predisposition. AB - Pregnancy outcome was investigated: 1) in fifteen women suffering from idiopathic recurrent spontaneous abortion (RSA) and who had experienced pregnancies with two different partners, and 2) in the mothers, the sisters and wives of the brothers of 90 consecutively referred women with RSA. After adjusting for ascertainment bias, the patients with 2 partners had an abortion rate of 72% with the first spouse (significantly increased compared with the expected rate) and a nearly 100% abortion rate with the second spouse. This suggests that, in the main, RSA is not partner-specific. The sisters of the patients had suffered a significantly increased miscarriage rate (25.3%) compared with the observed rate in a Danish control group. The wives of the brothers had an abortion rate of 18.8%, which was not significantly increased vis-a-vis the controls. The sisters showed a lifetime incidence of RSA (10.6%) which was significantly greater than comparable estimates in the literature. These results suggest the existence of a familial predisposition to spontaneous abortion in families where RSA occurs. PMID- 2094141 TI - Changes in beta-endorphin in fetal membranes and placenta in normal and pathological pregnancies. AB - Several studies indicated that trophoblast tissue synthesizes pro opiomelanocortin-related peptides. These peptides are also present in amniotic fluid, but their origin remains unknown. The present study evaluated the presence of and the possible changes in beta-endorphin (beta-EP) in amnion and chorion during pregnancy, at parturition and in spontaneous abortion. Amnion, chorion and placental tissues were isolated and homogenized from a total of 46 pregnant women between 4th and 42 th week of pregnancy. Beta-EP was separated on a Sephadex G-75 column and measured by RIA with specific antiserum. The identity of the endogenous opioid with its corresponding reference molecule was confirmed by high performance liquid chromatography. In all tissues, the concentration of beta-EP in the first trimester was significantly higher than in the second trimester. A negative correlation between opioid levels and gestational age was observed in the first two trimesters. At delivery, the beta-EP content of all tissues was greater than in the second trimester. In tissues collected at term, in the absence of labor, beta-EP levels were very low in comparison with those collected after vaginal delivery. Low beta-EP contents were found in membranes collected from spontaneous abortion in 1st trimester. From these data one can surmise the existence of a local endogenous opioid system in fetal adnexes. This system seems sensitive to the stress of vaginal delivery and could be involved in the mechanisms leading to spontaneous abortion. PMID- 2094143 TI - Inter-relationships of storage iron in the mother, the placenta and the newborn. AB - The influence of maternal storage iron and placental iron levels on the storage iron and serum transferrin levels in newborns, placental non-haem iron, serum ferritin and transferrin concentrations was studied in 72 mothers and their singleton healthy newborns following uncomplicated pregnancies. Serum ferritin and transferrin concentrations were measured using ELIZA and immunoelectrophoretic methods, respectively. Placental non-haem iron was measured chemically. Cord serum ferritin (142 +/- 68.6 micrograms/l) and transferrin (1.66 +/- 0.56 g/l) levels and placental non-haem iron concentrations (41.1 +/- 20.2 micrograms/g) were not correlated with the maternal serum ferritin levels (17.4 +/- 12.5 micrograms/l). No significant difference was observed in these parameters in the newborns of mothers with low (less than 10 micrograms/l) and high (greater than 20 micrograms/l) levels of serum ferritin. Thus mothers with a reduced store of iron at term can still manage to provide sufficient iron for the fetus. PMID- 2094142 TI - Zinc and birth weight in uncomplicated pregnancies. AB - The relationship between zinc status and birth weight in uncomplicated pregnancies was studied in 59 nulliparous and 27 multiparous Chinese women with singleton pregnancies, delivered at term. Maternal and umbilical cord blood, maternal pubic hair and a segment of the umbilical cord were collected at delivery for analysis. The zinc concentration was significantly higher (p less than 0.0001) in the plasma of newborn infants (13.9 +/- 2.8 mumol/l) than in maternal plasma (9.3 +/- 2.2 mumol/l), while the converse was found in tissue (60.8 +/- 17.0 vs 208.1 +/- 96.2 micrograms/g, p less than 0.0001). There was no significant correlation between birth weight and either maternal or newborn plasma or tissue zinc concentrations. Parity had no significant effect on maternal or newborn zinc concentrations in tissue and plasma. PMID- 2094144 TI - Uterine myoma in pregnancy. AB - A review was made of the medical records of 76 patients with uterine myomas during pregnancy with the aim of studying the time and method of diagnosis, symptomatology, treatment, and outcome of pregnancy. In 11 patients (15%) myomectomy was performed during pregnancy. The frequency of abortion was 18% in patients treated both conservatively and with myomectomy. Myomectomy during pregnancy is discouraged in the literature. In cases where conservative treatment cannot be practised it seems that the risk of spontaneous abortion during pregnancy is not significantly increased when myomectomy is performed. PMID- 2094146 TI - Blood pressure, metabolic variables and adipose tissue distribution in pre- and post-menopausal women. AB - The study was performed on 289 female patients (aged 20-60) of a family doctor in Castel D'Azzano, a small town near Verona. The following variables were considered: body mass index (BMI), tricepital, subscapular, hypomesogastric, epimesogastric, supra-iliacal and epitrochanteric skinfolds, waist, umbilical and bitrochanteric circumferences, cholesterol, triglycerides, HDL-cholesterol, glycemia, uricemia and blood pressure. A significant worsening with age was observed in the mean values of the variables. This worsening was particularly evident in women over 50. The population was subdivided according to presence or absence of menopause; the two groups were then matched for age. None of the variables showed significant differences. Our results did not confirm any of the many effects that menopause is supposed to have regarding metabolic and blood pressure alterations. PMID- 2094145 TI - Vaginal administration of PGE2 for induction of labor stimulates endogenous PGF2 alpha production. AB - Prostaglandin E2 is effective for induction of labor but many preparations exist using a variety of vehicles from which the active ingredient may not be equally available. Plasma concentrations of bicyclic PGE2 metabolite (PGEM) and 13, 14 dihydro, 15-keto PGF2 alpha (PGFM) were measured following administration of a 3mg PGE2 vaginal tablet or 1mg PGE2 vaginal gel to twenty-four parous women with favorable induction features, randomly allocated to receive one or other preparation. PGEM increased rapidly following both administration of the 3mg PGE2 vaginal tablet and the 1mg PGE2 vaginal gel, reaching a peak within 40 minutes of PGE2 administration. The maximal rise in PGEM in the gel group correlated directly with the change in cervical score and inversely with the need for augmentation with oxytocin and the induction-delivery interval. A secondary rise in PGFM was noted in both groups 3-4 hours following PGE2 administration. The magnitude of the increase in PGE2 may be important in the clinical response to PGE2 administration, while PGE2 absorption may switch-on endogenous PGF2 alpha production, similar to what is seen in spontaneous labor. PMID- 2094147 TI - Infertility, technology and the law. Patients' and future doctors' opinions. AB - The rectifying of infertility by application of modern technology has been a topic for debate in modern society over the past decade. Laws regulating the investigation and treatment of infertility have been passed in many countries, for instance in Norway and Sweden, while other nations await future developments. In this paper, some users of the technology--female infertility patients and future medical doctors--present their attitudes toward controversial issues of infertility, investigated by means of a survey questionnaire issued to them in 1987-88. Medical students have a more restrictive attitude than former patients, whereas religious beliefs influence the viewpoints of the patients. Both groups seem to have opinions that to a large degree accept the content of the Norwegian law. PMID- 2094148 TI - Cytobrush in evaluation of cervical dysplasia. Is cervical curettage necessary? AB - 203 patients suspected of having dysplasia were evaluated by colposcopy, cytologic smear including cytobrush, endocervical curettage, biopsy and conization. The results obtained on the basis of the final cone suggested that directed biopsies and cytological smear by spatula and cytobrush more accurately define the dysplastic lesion than do biopsies and endocervical curettage. Conization seemed necessary for the evaluation of the cervical lesion in patients revealing non-classified dysplasia at successive examinations. PMID- 2094149 TI - Reduced use of diagnostic obstetric ultrasound in Norway. Result of consensus panel recommending routine screening in pregnancy? AB - PURPOSE: To investigate the practice of obstetric ultrasound in Norway before and 2 years after a consensus conference recommending routine screening. Material, method: Two national representative materials sampled with a 2-year interval are compared. RESULTS: The average number of examinations was reduced from 2.46 to 2.2 (p = 0.014). Obstetrical institutions practising screening examined their patient less frequently than non-screening institutions (2.10 vs. 2.75 times, p less than 0.001 whereas in 1986 the converse was the case. CONCLUSIONS: Screening has become more widespread, and a more rational practice has developed. PMID- 2094150 TI - Aortic valve replacement during pregnancy. A case report and review of the literature. AB - Aortic stenosis (AS) is an uncommon complication during pregnancy, but when it occurs it results in significant maternal and fetal morbidity and mortality. We present a gravida with severe AS in which aortic valve replacement was performed in the 3rd trimester of her pregnancy. She had severe AS with mild aortic regurgitation and severe congestive heart failure. Fetal heart rate and uterine activity were monitored and recorded during the operation. The pregnancy was carried uneventfully to term and the patient was delivered of a healthy baby. The literature is reviewed and recommendations are made for the management of AS during pregnancy. PMID- 2094151 TI - Cervical pregnancy successfully treated with chemotherapy. AB - A case of cervical pregnancy in a 16-year-old woman is reported. Non-surgical management with actinomycin-D, methotrexate and cyclophosphamide chemotherapy resolved the pregnancy without significant morbidity. Subsequent pregnancy occurred with premature birth of viable normal infant. PMID- 2094152 TI - Carcinoma of the cervix in a pregnant woman with negative Pap smears and colposcopic examination. AB - A case is reported of squamous cell carcinoma of the cervix developing in a pregnant woman while manifesting five consecutive false-negative Pap smears and colposcopic appearance suggestive of dysplasia. Pap smears and colposcopic examinations are helpful in diagnosing dysplastic and early cancerous lesions of the uterine cervix. We describe a case where both Pap smears and colposcopy failed to diagnose an early occult invasive lesion in the cervix of a pregnant woman who manifested only CINIII by colposcopy, while the Pap smear was falsely negative on five consecutive occasions. PMID- 2094153 TI - Acute massive pulmonary embolism treated with streptokinase during labor and the early puerperium. AB - Acute massive pulmonary embolism occluding 60-70% of the pulmonary circulation occurred in a young primipara during the 28th week of pregnancy. She was critically ill despite 40 h of heparin infusion and thrombolytic therapy with streptokinase was initiated. After a 10-h infusion she went into labor and streptokinase treatment was stopped. One hour later she gave birth spontaneously to a preterm infant in footling breech delivery. The infant did well neonatally. Streptokinase infusion was recommenced 8 h after delivery. Because of increasing blood loss on the second day after delivery, streptokinase was withdrawn after a total treatment time of 29 h. Total hemorrhage amounted to 8.9 litres. Serial perfusion lung scans showed complete resolution of the emboli and normal lung function was restored. PMID- 2094154 TI - Unexpected survival after conservative management of cord prolapse in two very preterm babies. AB - Two very preterm infants (24 and 25 weeks) were born vaginally in spite of prolapse of the umbilical cord. The prolapses lasted 45 min and 2 h, respectively, but though both babies were at first believed to be lost, they survived, only mild to moderate asphyxia, and both were discharged well. One of the babies later developed slight neurological sequelae. Even a very preterm baby has the possibility of surviving vaginal delivery complicated by cord prolapse. PMID- 2094155 TI - Uterus didelphys associated with duplex kidneys and ureters. AB - In a patient with uterus didelphys, four kidneys and four ureters were detected. The sister too has a didelphic uterus. PMID- 2094156 TI - Early detection of primary carcinoma of the fallopian tube by endovaginal ultrasound. AB - About 0.5% of all gynecological malignancies in Sweden are primary fallopian tube carcinomas. Early diagnosis is difficult due to the paucity of symptoms. However, the diagnosis should be entertained in the presence of abnormal vaginal bleeding not explained by gynaecological examination and biopsy of the cervix and endometrium. The possibility of tubal carcinoma should be considered in patients with persistent vaginal discharge and lower abdominal pain without apparent explanation. An early case of fallopian tube carcinoma detected by endovaginal ultrasound is described. PMID- 2094157 TI - Establishment and characterization of new cell lines derived from gynecologic cancers with special reference to growth regulation by tamoxifen. PMID- 2094158 TI - Female genuine stress incontinence. A study with single cough urethrocystometry using a six-microtransducer catheter. PMID- 2094159 TI - Hirsutism in women of reproductive age: relations between hormonal and clinical parameters. PMID- 2094160 TI - Effects of psychosocial factors, especially work-related stress, on fertility and pregnancy. A prospective study from the stage of planning to become pregnant. PMID- 2094161 TI - [Complications of rhinoplasty]. AB - For an operation as technically demanding as rhinoplasty, surprisingly few studies have examined the results of this procedure. A retrospective study was, therefore, made of 5470 patients who had undergone rhinoplasty, performed by different surgeons, from 1970 to 1989. The patients were followed up for a minimum of one year. As for all forms of surgery, aspecific complications such as infections, hemorrhage and side-effects from anesthesia will occasionally occur but, fortunately, such cases are quite rare. The specific classification included both early and late complications. Post-rhinoplasty failures may be estimated at approximately 28% of all cases; this figure taking into account typical deformities, both minor and severe, as well as functional sequelae and patient dissatisfaction. Approximately 4% have required secondary procedures. Some causes for failure derive from patient characteristics; for example, the importance and complexity of initial deformity are, of course, partly responsible, particularly after trauma. The skin quality (i.e. thickness, or whether it is fatty or loose) also affects the results. Furthermore, uncontrollable factors inherent to healing (i.e. excessive scar contraction in the intranasal area, connective tissue hyperplasia, particularly at the tip, and periosteal proliferation either to the osteotomy site or over the nasal dorsum) can all lead to residual deformities. Nevertheless, most failures can be attributed the operator. The commonest mistakes are linked to cartilaginous dorsum and nasal tip (approx. 22%). There are several polymorphic deformities the main sites of which should be known well in order to prevent, or at least reduce, such risks. PMID- 2094162 TI - [Calcium accumulation in hyperpermeable fibers of vascular smooth, skeletal and cardiac muscle of rats]. AB - This work presents results on calcium accumulation capacity of chemically skinned multifiber preparations of aortic smooth, skeletal and ventricular muscle of the rat. The suppression of the plasma membrane functions as a permeability barrier to ions, allowed to expose the sarcoplasmic reticulum (SR) to 45Ca-EGTA buffers and to measure the amount of 45Ca accumulated by the preparations in a 30-min period at room temperature. The 45Ca loaded was attributed to the activity of the SR calcium pump since it was dependent on pCa values of the incubation media and enhanced by K oxalate. This method allowed to discriminate calcium accumulation capacity of SR in the different muscle types. 45Ca accumulated in the absence of K oxalate amounted to 5.16 +/- 0.08, 7.02 +/- 0.38 and 2.59 +/- 0.15 mumoles Ca2+/g fiber protein in aortic smooth, skeletal and ventricular muscle preparations, respectively. The values obtained in the presence of 10 mM K oxalate indicated the following increasing order of calcium accumulation capacities: skeletal greater than ventricular greater than or equal to aortic smooth muscle. Taking into account the protein content of each muscle type, the calculated amount of calcium accumulated by the SR exceeds that necessary to elicit full contractile activation. PMID- 2094163 TI - Effects of dietary lipidic charge in the concentration of bovine plasmatic lipids and lipoproteins. Its influence on the saturation degree of fatty acids' storaged lipids. AB - To estimate physiological changes due to added fat in bovine diet, whole cottonseed (19% lipids) was furnished to half-breed zebu cattle during 7 months. Thirty animals had increased its dietary lipidic charge in 2.6% (lot S), thirty were used as controls (lot C) and other two bovines were hyper-dosed with 7.9% added fat (lot H). Weight, clinical signs and plasmatic values of total cholesterol (TC), triglycerides (TG), lipoproteins (LP) and other biochemical parameters were monthly controlled. At the end of the assay the steers were sacrificed and the quality of meat and fat was evaluated. The initial levels of TC were statistically homogeneous in all groups (mean = 1.0 g/l); they remained without modifications in C (1.53 g/l), but they had increased progressively in supplemented animals. At the end of the work TC was greater in H (3.95 g/l) than in S (2.44 g/l). Latest TG (initial mean = 0.30 g/l) also were greater in H (0.74 g/l) than in S (0.71 g/l). The lipoproteinogram stayed inalterable in C, meanwhile alpha LP were increased and beta LP were decreased in animals on which the dietary lipidic charge had been increased. The weight's gain/animal/day (X) was 130 g (C), 290 g (S) and 88 g (H). The general physiological condition was deteriorated in the last lot. After comparing lots C and S, results indicated that beefsteaks in the last group were heavier (2.45 vs. 2.33 kg), with more lipids (0.47 vs. 0.36 kg) and major fat veined proportion (1.40 vs. 1.25%). The stored lipids showed high saturation degree in S, with increment in the mean percentage of stearic acid (28.6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094164 TI - Depressed plasma erythropoietin levels in rats with hemodynamically-mediated acute renal failure. AB - Adult female Wistar rats were injected with 125 mg/kg b.w. of human methemoglobin (M-Hb) in order to induce a first episode of hemodynamically-mediated acute renal failure (HMARF). Eleven days after the injection of M-Hb, other groups of rats received another equal dose of the drug in order to induce a second episode of HMARF. Evaluation of renal function, histopathology studies, and determinations of plasma and kidney erythropoietin (Epo) titers by radioimmunoassay in normoxic and hypoxic conditions were performed 1, 2, 3, 5 and 10 days after M-Hb administration. Treatment induced transient increases in plasma urea concentration, fractional sodium excretion, and urine volume, and significant depression in urine osmolality. In every case, the maximal effect of the first injection of M-Hb on the individual parameters was always greater than that of the second injection, and observed on the 5th post-injection day. Histologic sections showed interstitial cellular infiltration, desquamation of the proximal tubular epithelium and collapse or dilation of the tubular lumen. Treatment with M-Hb depressed Epo titers in both kidney homogenates and plasma in normoxic as well as hypoxic rats. Here again, the effect of the first injection of the drug was higher than that of the second one. These observations indicate that there is a negative correlation between kidney tubule injury and Epo production in normoxic and hypoxic conditions. The findings give support to the concept that Epo production is related to proximal tubular function. PMID- 2094165 TI - The mouse spleen white pulp response to continuous hypoxia. A digital image processing analysis. AB - Ninety days old male mice of the CFW strain, placed under standard conditions for studies of periodicity, showed a 24 hours variation pattern in the spleen white pulp surface, in cross sections. This pattern was modified by hypoxia during the first 18 hours of continuous treatment. Since this time onwards a new steady state was reached, although the spleen of hypoxic animals was always smaller than in the controls. As the modifications were measured in pixel counts -a magnitude which can be easily transformed into square micrometers- they can be attributed to a real size variation and not to an apparent growth and decay due to environmental vasoactive phenomena. PMID- 2094166 TI - [Blocking of the alpha rhythm induced by sensory self-stimulation]. AB - In a series of experiments in animals and in man several authors have shown that sensory stimulation induces low voltage fast activity in the EEG. The problem to be studied in this work is related to the EEG changes produced by self stimulation. A group of human subjects were instructed to be self-stimulated with clicks and flashes of light randomly applied by themselves. When the subjects were with the eyes closed and in resting state, alpha rhythm was predominantly recorded in the EEG. However, during acoustic or visual stimulation a low voltage fast activity was predominantly observed in the EEG. In self-administration of the stimulus a low voltage fast activity was recorded in the EEG several seconds before the stimulus application. These results suggest that the activation of a complex neuronal mechanism involved in the volitive response, as well as anxiety and attentive states of the subject occurring before the actual stimulation to select the moment at which the stimulus has to be applied, can be responsible for the blocking of the alpha rhythm previously to the flashes of light and clicks presentation. PMID- 2094167 TI - [Norepinephrine-sensitive calcium pools in tail arteries of normotensive and spontaneously hypertensive rats: effects of ryanodine and caffeine]. AB - The effects of Ryanodine (RY) and Caffeine (CF) on the norepinephrine (NE) induced contraction were studied in tail artery rings from spontaneously hypertensive rats (SHR) and normotensive, Wistar Kyoto rats (WKY). The NE sensitive intracellular store of calcium was completely depleted by NE (1 microM) in calcium-free physiological salt solution (Ca = 0-PSS), and accounted for approximately 40% of the total response to NE in regular PSS (Ca = 1.6 mM). However, only 60% of the NE-releasable store was utilized for the full contraction in PSS. Re-exposure to PSS completely replenished the NE-releasable store in 10 minutes. Over twice as much calcium appeared to be taken up by the SHR as by the WKY arteries in these conditions. RY prevented the refilling of the NE-sensitive calcium store in both SHR and WKY, without releasing calcium from the store and without affecting the influx of calcium through membrane pathways. CF also prevented the refilling of the NE-sensitive calcium store, but did release calcium from it. It can be concluded that: 1) Whereas the main action of RY on rat tail artery seems to be the inhibition of calcium uptake by the sarcoplasmic reticulum (SR), CF has several actions: a) inhibition of calcium uptake by the SR, b) release of calcium from the SR, and c) opening of calcium channels in the plasma membrane of the smooth muscle cell. 2) In SHR, but not in WKY, the loss of calcium from the membrane in Ca = 0-PSS renders it more permeable to calcium, permitting an enhanced calcium uptake during subsequent exposure to PSS. PMID- 2094168 TI - Effect of 11 beta OH pregna-1,4-diene-3,20-dione (delta HOP) on thymocyte plasma membranes. AB - The effect of delta HOP on the formation of concanavalin A (Con A) caps and steady state anisotropy (rs) obtained in 1,6-diphenyl-1,3,5-hexatriene (DPH) labeled thymocyte plasma membranes was compared with the effect of glucocorticoids on these experiments. Results demonstrate that delta HOP decreased cap formation "in vivo" as well as "in vitro" and that it did not change fluorescence anisotropy "in vitro". Glucocorticoids had an opposite effect, increasing fluidity apparently through a glucocorticoid specific mechanism not exerted by delta HOP. PMID- 2094169 TI - [Body weight and adrenal function in rats with "foster mothers" from the moment of birth]. AB - In rats, the effect of the separation from their mothers on the corporal weight and on the levels of adrenal hormones, adrenal and plasmatic corticosterone and adrenal catecholamines was studied. The litters were grouped according to: a) maintained with their biological mothers, and b) maintained with their mothers interchanged immediately after birth (foster mother). All were lactating mother rats. In group b) the corporal weight was lower (p less than 0.001) than in group a) from the 14th to the 28th day of life, their weight increased thereafter. The levels of adrenal corticosterone were higher (p less than 0.01) in group b), but the plasmatic corticosterone levels were similar to that in group a). With respect to catecholamines, the noradrenaline values were higher in group b) (p less than 0.001), whereas the adrenaline levels were lower (p less than 0.01) than those in group a). PMID- 2094170 TI - [Capgras syndrome or delirium of doubles. Presentation of a new case]. AB - Capgras syndrome is an unfrequent delusional disorder based on the patient's belief that a significant person for him or her, mainly the spouse, becomes a "double", undistinguishable from the real one, but threatening in some way. There are about two hundred reports of the syndrome in international psychiatric literature. This paper describes a new case in a woman aged 68, diagnosed of Major Affective Disorder, without signs of any other organic mental disease. The authors review some ethiological theories in relation with the disorder, which are contrasted with the characteristics of the new case. PMID- 2094172 TI - [Sociodemographic and occupational aspects of public assistance demand for problems related to alcohol]. AB - Bibliographic quotations on alcohol related problems in Castilla y Leon, and some socieconomic data on income, annual revenues, sectorial brute outputs, vine culture surface, red and white wine production in Valladolid, regional enterprise export and evolution are reported on introduction. Characteristics and limitations of the utilized notifications system and number of alcoholic (N = 433) and psychiatric cases (N = 2788) by institutions during 1986-1987 period are summarized. Notification rates, ranking between 1,08 0/000 at risk, and risk populations by province are reported at results section. Differences between alcoholic and remainder psychiatric patients were evaluated with regard to sex, marriage status, education, labour activity and consultation age. Significant differences (p less than or equal to 0.01) of morbidity between alcoholic and remainder psychiatric patients were found at the following intervals of age: 15 24 (4.7% alcoholic vs. 13.7% psychiatric patients), 25-34 (21.6% alcoholic vs. 18.9% psychiatric patients), 35-44 (26.0% alcoholic vs. 16.7% psychiatric patients), 45-54 alcoholic vs. 15.9% psychiatric patients) and older than 65 (6.6% alcoholic vs. 15.2 psychiatric patients). Significant differences (p less than or equal to 0.001) are also observed between alcoholic and psychiatric patients at male (89.8% alcoholic vs. 43.9% psychiatric patients) and female (10.2% alcoholic vs. 56.1% psychiatric patients) categories. Significant differences (p less than or equal to 0.01) are found at window (2.6% alcoholic vs. 7.7% psychiatric patients) and separated couples rates (8.6% alcoholic vs. 2.5% psychiatric patients). With regard to education there are significant differences between first school (32.8% alcoholic vs. 26.28% psychiatric patients (p less than or equal to 0.01), high school (5.0% alcoholic vs. 9.53% psychiatric patients, p less than or equal to 0.05) and university studies (2.5% alcoholic vs. 5.52% psychiatric patients, p less than or equal to 0.05). There is a different professional profile in alcoholics. Manager, and liberal professional rates (7.09% alcoholic vs. 10.93% psychiatric patients) are significantly different (p less than or equal to 0.01) between white collar worker (11.98% alcoholic vs. 4.92% psychiatric patients), technician (16.87% alcoholic vs. 8.85% psychiatric patients) and blue collar worker rates (65.53% alcoholic vs. 26.97% psychiatric patients). Figures of retired are lesser (p less than or equal to 0.05) in alcoholic than in psychiatric patients (12.67%) and people %ho make home work are lesser (p less than or equal to 0.01) in the former (5.54%) than in the latter (35.37%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2094173 TI - [Emotional expressiveness and development of schizophrenia: a reply to the work of Vaughn]. AB - The influence of family climate in the course of schizophrenia has been empirically established. However research has been so far limited to the Anglo American culture and there are reasons to think that straight forward extrapolation to own our culture may not be totally justified. Consecqently a replication of Vaughn's (Vaughn et al, 1984) has been carried out with a sample of 60 schizophrenic patients in Valencia. Relapse rate was not predicted by EE status or by any EE scale-score according to British original criteria. As the cut-off point was changed from six or more critical remarks to four or more, then the relapse rate was significantly different between high and low EE groups. The study confirms the link between EE-status and relapse rates over nine months but is also underlines the need to take into account cultural differences when it comes to establish cut-off scores. PMID- 2094171 TI - [The personality of wives of alcoholic patients]. AB - This work is a study of the personality of the wives of alcoholic patients composed by means of a structures interview, the MMPI personality questionnaire and the Instrument I used to evaluate aggressivity. Among the discoveries made, we must emphasize that 20% of the wives knew of their partner's excessive alcohol consumption before marriage, while married, 75% were victims of some kind of violent incident, 43% had personal psychopathological backgrounds, 15% were "repeaters wives" "those who had alcoholic parents). In the MMPI test, these women represent a significantly high profile, in which the scales Hs, D and Hy are the highest, amongst which their most outstanding personality traits include passivity, dependency and insecurity. Furthermore, those wives whose husbands have had relapses, represent a higher Pd scale than the other group. The Instrument I used to evaluate aggressivity also emphasizes this passive aggressive tendency in the wives. PMID- 2094174 TI - [Description and validity of Enedam test-retest. A structured interview for the diagnosis of Alzheimer's, multi-infarction dementias and dementias of other etiologies based on the CIE-10 and DSM-III-R]. AB - The SIDAM, a new clinical structured interview for the diagnosis and measure of dementia according to DSM-III-R and ICD-10, is described. This instrument comprises a clinical overview, several cognitive tests, including the Mini-Mental State, and a section for clinical judgement and information coming from others. Every item relies on DSM-11-R and ICD-10 algorithms. The SIDAM has a hight test retest reliability on the clinical diagnosis and the different diagnostic criteria. It is a brief (28 minutes), practical screening instrument. Good congruence is found between SIDEM, DSM-III-R and ICD-10, and the corresponding ICD-9 expert diagnosis. Furthermore the SIDAM Total Score (SISCO), allows a good measurement of low level of cognitive impairments and provides quantification of severity of cognitive disorders. The SIDAM has been translated and adapted into Spanish. PMID- 2094175 TI - [Psychiatric evaluation of organic diseases]. AB - The psychiatric assessment of the patients with organic illnesses is very difficult because of the bias related to physical symptoms (asthenia, anorexia). This could produce an over-diagnosis of the psychiatric disorders. The use of the specific psychiatric diagnosis criteria in the organic illnesses avoids this kind of problems and allows an improvement of their clinical assessment. PMID- 2094176 TI - Taking the sting out of postoperative analgesia in children. PMID- 2094177 TI - Phospholipases A2: a dendrogram from a distance matrix based on size and hydrophobicity of the residues in their homologous sequences. AB - A distance matrix was obtained from aligned homologous sequences of 32 phospholipases A2 (EC 3.1.1.4) (24 from Elapid and 5 from Viperid venoms, and 3 from mammals), on the basis of the quantities Dij which are defined from a two dimensional vector representation of the amino acid residues (dimensions: size and hydrophobicity). These Dij quantities were proposed in a previous paper (Ventura, M. M., (1989), An. Acad. brasil. Ci., 61: 215). A dendrogram was constructed from this distance matrix employing, for cluster analysis, the unweighted pair-group using arithmetic averages. Two groups of phospholipases A2: a) Elapid venom enzymes together with the three mammalian pancreatic enzymes (bovine, equine and porcine), and b) Viper venom enzymes (Crotalus, Trimeresurus and Bitis enzymes) can be well distinguished in the topology of the dendrogram. The Elapid group of enzymes is divided into two subgroups: a) Naja, Hemachatus and Bungarus venom enzymes, and b) Notechis, Laticauda, Enhydrina and Oxyuranus venom enzymes. It is observed that there is a close similarity between the mammalian pancreatic phospholipases A2 and the enzymes from Naja, Hemachatus and Bungarus. These results are similar to those reported by Dufton and Hider (Eur. J. Biochem., 137:545 (1983] which were obtained from the distance matrix based on minimum mutation distance between 25 selected residue positions in the pairwise compared sequences. PMID- 2094178 TI - [Selection by means of KB cells of substances and extracts potentially active in cancer chemotherapy]. AB - Several synthetic, semi-synthetic and natural compounds as well as plant extracts were screened for their growth inhibition activity on KB cells. The most active ones were naphthoquinones and derivatives of pyrido [4,3-b]carbazole alkaloids, with inhibition dose (ID50) less than 4 micrograms/ml. Of the crude extracts of several plants screened, Vellozia caput-ardeae showed to be the most active. PMID- 2094179 TI - Immunochemical localization of the fraction-1 antigen, a virulence determinant of Yersinia pestis. AB - The distribution of Yersinia pestis Fraction-1 (F1) antigen was analyzed in cells grown at 28 degrees C and 37 degrees C. Fractionation of Y. pestis cells followed by analysis in SDS-polyacrylamide gel electrophoresis indicated that the mature form of the F1 antigen is localized in the extracellular matrix and in the cytoplasm. Localization of the F1 antigen was confirmed by immunoblots and a single peptide with a molecular weight of 17,000 daltons was recognized. Electron microscopy of Y. pestis cells labeled with colloidal gold-conjugated antibodies corroborated the extracellular matrix and cytoplasm dual location of the F1 antigen. PMID- 2094181 TI - [Cryptogenic cirrhosis. The tip of the iceberg]. PMID- 2094180 TI - [Records of clinical research of the Instituto de Gastroenterologia de Sao Paulo IGESP and the Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia- IBEPEGE]. PMID- 2094182 TI - Cryptogenic cirrhosis: clinico-biochemical comparison with alcoholic and viral etiologies. AB - Cryptogenic cirrhosis defines a group of undetermined etiology that would either be caused by factors as alcohol, virus and others or be due to still unknown etiological factors. To test these hypotheses we have looked for similarities or differences in clinico-biochemical presentation of 196 cases of alcoholic, viral and cryptogenic cirrhosis. Age, jaundice, spiders, palmar erythema and factor V showed a statistically significant difference of the cryptogenic cirrhosis when compared with both alcoholic and viral etiologies. On clinico-biochemical grounds it could be suggested that cryptogenic cirrhosis would constitute a discrete group, based on the following parameters: predominance of females, a more advanced age, less marked peripheral signs of chronic hepatic failure (jaundice, spiders and palmar erythema) besides milder alterations of laboratory liver function tests. PMID- 2094183 TI - [Carcinoid tumors of the gastrointestinal tract. Analysis of 21 cases]. AB - Twenty-one patients with carcinoid tumors have been analysed. Out of 18 patients the diagnostic was made at operation and out of 3 by autopsy. The most frequent sites of the primary tumors were the appendix (38.1%), ileum (23.8%) and colon (19.9%). Asymptomatic tumors were found incidentally in 10 patients (55.5%). The symptomatic neoplasms were more common in the ileum. No one patients in this series obtained the diagnostic of carcinoid tumors before operation or autopsy. It was not observed the malignant carcinoid syndrome. Sixteen patients (88.8%) were submitted to resection and the mean survival was 10.7 years. Two patients (11.1%) were submitted to palliative operations and the mean survival was 3.5 months. The incidence of metastases in cases with carcinoid greater than 2.0 cm in diameter was 71.4%; on the other hand, the patients with carcinoids 2.0 cm in diameter or smaller than this size disclosed metastases in 7.6%. No patients with appendix carcinoid showed metastases and all patients with metastases presented ileum or colon carcinoids. In this series, the prognostic was related with the lesion's size, the localization of the tumor in the gastrointestinal tract and with the resection or not of the primary neoplasm. PMID- 2094184 TI - [Fecal excretion of fats and nitrogen in rats with niacin deficiency]. AB - The effect of dietary-induced niacin deficiency on intestinal absorption of fat and nitrogen was studied in 18 rats through the metabolic balance technique. When compared with de control group (n = 9) the niacin deficient rats (n = 9) showed higher fecal fat and nitrogen output. The former was diarrhea-dependent and the later diarrhea independent processes. It is suggested that niacin deficiency might induced an early impairment in the intestinal protein absorption followed by diarrhea which would account lately for the fat malabsorption. PMID- 2094186 TI - Computed tomography in neurocysticercosis: a 10-year long evolution analysis of 100 patients with an appraisal of a new classification. AB - Three hundred and fifty seven computed tomography (CT) from 100 different patients with neurocysticercosis (NC) were studied between 1979 and 1988. All patients were treated with praziquantel (PZQ). A new classification attempting to recognize the CT evolution profile in NC as well as assigning a possible link between CT findings and biological conditions of cysts is evaluated. It was possible to conclude that: intact cysts remain unchanged in consecutive CTs by 11 months and exhibit signs of degeneration in about 18 months after PZQ drug therapy; degenerating cysts can be detected by 10.5 months, disappear in 11 months and become nodular calcifications in about 25 months. Therefore, a time period of at least 36 months can be estimated for the complete evolution profile of cysts in the brain parenchyma. PMID- 2094185 TI - [Anatomo-histological and histochemical study of acute lesions of the gastroduodenal mucosa, produced by ethanol, before and after truncal vagotomy plus pyloroplasty in rats]. AB - The anatomo-pathologic alterations determined by ethanol in the gastroduodenal mucosa of rats are studied, as well as its action about truncal vagotomy plus pyloroplasty (VT + P). We use albino rats submitted to the administration of ethanol, 33% --via orogastric catheter- and to truncal vagotomy plus pyloroplasty, as well the association of the 2 variants. The utilization of ethanol, according to the up to date methodology, can be confirmed by a simple experimental production method of acute ulcer in rats. The VT + P determined acute ulcers in the 24 hour observation group, besides acute inflammatory lesions and with the decrease of mucins, diffusively, in the gastroduodenal mucosa. The performance of VT + P, 2 hours after the administration of ethanol, period in which the lesions are entirely settled, determined and aggravation of the gastric lesions through the increase of the media ulcerous gastric area and its histological aspects. On the other hand, the performance of VT + P, followed by the administration of ethanol 2 hours after, also determined an aggravation of gastric lesions, according to the same former parameters. When it was the time to perform the VT + P, 10 days before the administration of ethanol, or the inverse, a small reduction at the ulcerous gastric area had accrued but it did not amount to much. There was not a characterization of preventive effects or curative of this surgical procedure considering the gastric lesions produced by ethanol, but there was characterization of aggravating effect. All the possible hypothesis to the aggravation of these lesions are also discussed with the utilization of VT + P, as well its clinical use on the human being. PMID- 2094187 TI - Neurocysticercosis: an epidemiological survey in two small rural communities. AB - The authors describe the epidemiological findings related to human taeniasis and cysticercosis, and swine cysticercosis in two small rural communities, Postinho (P) and Tigre (T), of South Brazil. The prevalence of epilepsy was 2.04% (P) and 2.25% (T). The prevalence of neurocysticercosis was 0.47% (P) and 0.93% (T), and prevalence of swine cysticercosis was 12.8% (P) and 27.8% (T). Taenia sp. infestation was detected in 4.3% (P) and 4.6% (T) of stool examinations. The hyperendemic human taeniasis and cysticercosis and swine cysticercosis seems to be related to poor hygienic habits of the population, and the free access to human excreta by the pigs. PMID- 2094188 TI - [Treatment of neurocysticercosis with praziquantel]. AB - Twenty seven patients with neurocysticercosis were treated with praziquantel in progressive doses reaching 50 mg/kg/day associated with dexamethasone for 21 days. The patients were followed during and after treatment and those followed up for one year repeated their immunological tests (indirect immunofluorescence and ELISA) at this time. Headache was the most frequent symptom during the treatment, occurring on 37% of patients. During the treatment 18.5% of patients had intracranial hypertension and one died. One year after treatment 72.2% of patients who finished treatment improved. The immunological tests became negative in 45.4% of patients sera and 42.8% of cerebrospinal fluids. There was no correlation between the clinical evolution and immunological tests. In this study it is not possible to affirm that both negative immunological tests and good clinical evolution were consequent to the efficacy of praziquantel treatment. Due to the great frequency and seriousness of this treatment complications, the patients with neurocysticercosis must be individually evaluated to know the risks and the benefits of the treatment with praziquantel. PMID- 2094189 TI - [Neurocysticercosis in the State of Espirito Santo, Brazil: evaluation of 45 cases]. AB - We analyzed the clinical course, laboratory tests, evolution, and epidemiological features of 45 patients with the diagnosis of neurocysticercosis (NC) referred to Neurology Service of Hospital Cassiano Antonio Moraes, Universidade Federal do Espirito Santo, from January 1987 to January 1989. This study represents the first survey of that pathology in the State of Espirito Santo, and has led us to conclude that neurocysticercosis is endemic in this part of the country. The diagnosis was based on clinical features, CSF abnormalities proper to NC and cranial CT scans to search for cysts, calcifications and ventricular abnormalities. The diagnosis of NC was corroborated by the finding of at least two of these criteria. No statistical differences were found for sex and/or age distribution. Intracranial hypertension and epilepsy were among the most common clinical symptoms. The treatment was adequate to each patient, and varied from symptomatics to specifics. Praziquantel (PZQ), as well as surgery when indicated (ventricular-peritoneal shunt and/or cysts resection) were used. No statistical differences were found in the follow-up of the patients who were under PZQ alone and those who used PZQ plus steroids (associated). Surgery was of great benefit for those patients with intraventricular NC and severe intracranial hypertension. All patients were under close observation on periodical clinical visits during the time of this study, and we have demonstrated that neurocysticercosis is a strongly recurrent endemic pathology. PMID- 2094190 TI - HTLV-1 antibodies in serum and cerebrospinal fluid in tropical spastic paraparesis in Brazil. AB - HTLV-1 antibodies were investigated in serum and in CSF of 150 patients with neurologic disorders mainly myelopathies. The patients were considered into three groups according to the possible relationship of their disease to the presence of HTLV-1 antibodies: no relationship risk (control group), occasional risk group, and possible risk group. In this latter are 56 patients with crural spastic paraparesis or paraplegia of unknown etiology (SP). HTLV-1 antibodies were tested by the passive particle-agglutination method for anti-ATLA antibody detection. The search was negative in all patients of the control group, and positive (serum and/or CSF) in 16.5% of the patients from the second group and in 55.4% of the SP patients group. Clinical patterns in SP cases with HTLV-1 antibodies were those of tropical spastic paraparesis (TSP). CSF patterns considered (cytology, protein content and gamma-globulins rate) were different between TSP group with HTLV-1 antibodies in CSF and SP group with no HTLV-1 antibodies detection either in serum or in CSF. The difference was significant. Results of this investigation confirm the high incidence of TSP in Brazil, and bring additional indication for searching HTLV-1 antibodies in the CSF. PMID- 2094191 TI - [Microsurgical anatomy of the anterior choroidal artery]. AB - Microdissection of 100 hemispheres from human cadavers were performed in order to study the anatomic characteristics of the anterior choroidal artery (AChA). One AChA per hemisphere was found. In 98% of hemispheres the AChA arose from the internal carotid artery (ACI) 2.4mm distal to the origin of the posterior communicating artery (ACoP) and 4.7mm proximal to the carotid bifurcation. One or more perforating branches arose from communicating segment of ACI in 29% of hemispheres. The average calibre of the cisternal portion was 0.9mm and the plexal portion 0.7mm. The most frequent branches of the cisternal portion pass to the optic tract, cerebral peduncle, uncus and lateral geniculate body. Anastomosis were found between branches of the AChA and posterior cerebral artery, ACoP, middle cerebral artery and ACI. The results are discussed. PMID- 2094192 TI - [Dystrophin in the differentiation between Duchenne and Becker muscular dystrophies: an immunohistochemical study compared with clinical stage, serum enzymes and muscle biopsy]. AB - Study of 55 cases of progressive muscular dystrophies (34 Duchenne, 12 Duchenne with residual dystrophin and 9 Becker patients) comparing age, age at the initial symptoms, duration of symptoms, levels of serum enzymes, degree of disability measured by the Vignos and Archibald scale, and the type and amount of dystrophin found in the muscle biopsies by immunofluorescence. Statistical analysis showed a tendency of the symptoms and progression of disease to be related with the low quantity of dystrophin in the biopsies. There was no difference in the parameter analysed between the Duchenne patients with and without residual dystrophin, as well as the Duchenne with residual dystrophin and Becker patients. There was an inverse relation with the amount of dystrophin and the endomysial connective tissue and fatty infiltration, and a direct relation with hypertrophic fibers and atrophic angulated fibers in the NADH-tetrazolium reductase. In the comments a discussion is made about the difficulties in differentiate Duchenne and Becker dystrophies, the cases with residual dystrophin and the importance of the correct diagnosis. PMID- 2094193 TI - Cerebrospinal fluid and serum antiphospholipid antibodies in multiple sclerosis, Guillain-Barre syndrome and systemic lupus erythematosus. AB - Immunoglobulins isotypes (IgG and IgM) for myelin basic protein (MBP), cerebrosides (CER), gangliosides (GANG) and cardiolipin (CARD) were detected in the cerebrospinal fluid (CSF) from 33 patients with multiple sclerosis (MS), 18 with Guillain-Barre syndrome (GBS) and 30 with systemic lupus erythematosus (SLE). In MS patients occurred positive and significant levels of IgG-MBP in 51.5% (p less than 0.05) and IgM-MBP in only 18.2%, IgG-CARD in 46.2%, as long as CER and GANG were detected in almost 20%. From serum samples of MS patients 20.6% presented IgG-MBP, while 53% showed positive levels for IgM-MBP. The CSF analysis of patients with GBS showed that 56.3% revealed IgG-MBP (p less than 0.05), 53% for IgM-MBP, 38.5% for IgG-CER and 23% for IgM-CER, while 50% of patients had IgG CARD, as long as 31% also had IgG-GANG. The serum evaluation from 14 patients showed that 18.8% had positive concentrations of IgG-MBP and 56.3% presented IgM MBP (p less than 0.05). Except for 50% of patients with SLE who presented positive CSF levels of IgG-CARD, only 24.1% had positive levels of IgG-MBP. We believe that the presence of antiphospholipid antibodies in CSF of the above mentioned diseases occurred as immune epiphenomena, but their appearance would permit the maintenance of and perpetuate the immune event. PMID- 2094194 TI - [Dura mater displacement in lateral cisternal punctures]. AB - Report of an anatomic study of the lateral cisternal punctures (at the atlanto occipital and C1-2 interspaces), carried out on fresh cadavers. Direct visualization of the internal surface of the dura mater (DM) at the cranio cervical junctions was possible by removing the calvarium and brain (sectioned at the upper cervical spinal cord). Dislocation ("tenting") of the DM over the needle was observed in all occasions (n = 42), measuring 3.46 mm (2-6 mm). PMID- 2094195 TI - [Reduction in glucose concentration in the brain of mice inoculated with cerebrospinal fluid from patients with amyotrophic lateral sclerosis]. AB - Using chromatographic analysis the authors studied glucose concentration in the brain of Swiss mice inoculated with CSF of four patients with amyotrophic lateral sclerosis. They found reduction in the levels of glucose, suggesting the existence of an exogenous factor transferred by CSF. PMID- 2094196 TI - [Spinal cord infarction: clinical, electrophysiologic and laboratory diagnosis]. AB - In the international, but more so in the latin-american, medical literature infarction of the spinal cord has been rarely described except in relationship with surgery of the abdominal aorta. The objective of this report is to describe the diagnostic approach including clinical, electrophysiological, imaging and cerebrospinal fluid criteria. With these methods 17 cases were diagnosed between 1982 and 1989, one related to surgery of the abdominal aorta. This series suggests that infarction of the spinal cord is a more common clinical entity than presently considered. Its rarity may be due to a high diagnostic threshold related to the perception that there is no specific therapy. PMID- 2094197 TI - [Rett syndrome: report of 7 cases]. AB - The authors report the clinical and laboratory findings of seven girls with the diagnosis of Rett syndrome seen at the clinic from August 1978 to October 1988. The patient's age varied from two to ten years and they were followed up for 5 years and 9 months in average. The development milestone started to deteriorate between five and twenty-four months. Acquired microcephaly was present in six patients and three cases had hyperventilation. Generalized tonic-clonic seizures were the most frequent type of seizures (6 patients) beginning between one and seven years and effectively controlled with carbamazepine. The EEG's abnormal findings were spike discharges (5 patients) and paroxysmal high-amplitude theta activity (4 patients). The remaining laboratory tests were unremarkable. The pathogenesis of Rett syndrome has not been determined. The clinical evaluation is intended to contribute to the knowledge of that rather uncommon disease. PMID- 2094198 TI - [Primary brain neoplasms associated with vascular malformations: anatomo pathologic study of 2 cases]. AB - The association of intracerebral vascular malformations and primary cerebral neoplasm is rare. The most commonly found vascular malformation with neoplasm is intracranial arterial aneurysm. We describe two cases of vascular malformations associated with primary cerebral neoplasms, with histologic and immunohistochemical studies. PMID- 2094199 TI - Wall-eyed bilateral internuclear ophthalmoplegia (Webino syndrome) and myelopathy in pyoderma gangrenosum. AB - A 35-year-old female with pyoderma gangrenosum developed paraparesis with a sensory level at L1. Three months later she complained of diplopia and was found to have bilateral internuclear ophthalmoplegia with exotropia and no ocular convergence. The term Webino syndrome has been coined to design this set of neuro ophthalmologic findings. Although it was initially attributed to lesions affecting the medial longitudinal fasciculus and the medial rectus subnuclei of the oculomotor complex in the midbrain the exact location of the lesion is still disputed. In the present case both myelopathy and Webino syndrome were probably due to vascular occlusive disease resulting from central nervous system vasculitis occurring in concomitance to pyoderma gangrenosum. PMID- 2094200 TI - [Association of Wilson's disease with non wilsonian extrapyramidal syndrome in the same family]. AB - Movement disorders, mostly dystonia, sometimes occur in heterozygotes for Wilson's disease (WD). A patient with metabolic abnormalities suggestive of heterozygote for WD and dystonia is reported. His niece showed the typical neurological and metabolic abnormalities of WD. This rare coincidence and the etiopathogenic mechanisms involved are discussed. PMID- 2094201 TI - [An unusual association: polymyositis, myasthenia gravis and thymoma]. AB - Based on the inexistence of references in Brazilian and International literature of the association polymyositis, myasthenia gravis and thymoma in a young male adult, the authors propose to describe one case presenting the associated syndrome. The disease began when the patient was 22 years old, being the climax of its clinical expression four years later. It is emphasized the difficulty on the differential diagnosis between polymyositis and myasthenia gravis, once these diseases frequently have their clinical manifestations well individualized. In this study we call attention to the existence of clinical aspects of myasthenia gravis in patients presenting polymyositis and, on the other hand, histopathological alterations typical of polymyositis in myasthenic muscles, what makes the clinical diagnosis uncertain many times. PMID- 2094203 TI - Quality assurance: much ado--much to do. PMID- 2094202 TI - The evaluation of group education for patients with non-insulin dependent diabetes at Hollywood Repatriation Hospital in Western Australia. AB - OBJECTIVES: To enable effective use of hospital resources in relation to staff time and diabetes education; to ensure that all patients have access to a standard level of education; and to maintain and/or improve diabetes control. METHOD: Multiple choice questionnaire to test knowledge; check of individual biochemical status. RESULTS: Diabetes knowledge and control were assessed in 51 persons with non-insulin dependent diabetes mellitus (NIDDM) attending diabetes group education sessions at Hollywood Repatriation Hospital in Western Australia. The programme comprising three 2.5 hour sessions at weekly intervals, was conducted by the physician, dietitian, nurse educator, podiatrist and physio therapist. Groups consisted of 7-14 patients, with partners encouraged to attend, and aimed to promote and stimulate discussion on diabetes self-care among participants. After group education there was a significant improvement in knowledge of diabetes, blood sugar control and energy balance. This was achieved with a reduction in staff time, when compared with individual education, and a more efficient use of hospital resources. Thus, the objectives were realized. It is concluded that diabetes group education is useful in patients with NIDDM attending Hollywood Repatriation Hospital. PMID- 2094205 TI - From the perspective of contributors to the first issue of Australian Clinical Review. PMID- 2094204 TI - From the perspective of the medical colleges. PMID- 2094206 TI - The Professional Component Index: a model for the professional remuneration of pharmacists. PMID- 2094207 TI - The review of the implementation of quality assurance in Victoria. PMID- 2094208 TI - [Orthopedic aspects of Crohn disease. Examples of extra-intestinal organ manifestations]. AB - Articular changes in Chron's disease represent extraintestinal organic manifestations which generally take the form of so-called enteropathic synovitis. Articular alterations - diagnosed as non-specific arthritis in the great majority of cases--may precede the intestinal disease. In very rare cases it can be shown that the joints display histological changes typical of Morbus Crohn. The etiology and pathophysiological mechanisms of the articular changes are not clear. Probable factors are: autoimmune disease, stimulation of the immunological system by exogenous antigens, induction of a self-sustaining inflammatory process, and demonstrable circulation of antigen-antibody complexes. Genetic factors seem to play a role (familial disposition). A pure "colonic Crohn" (= colitis granulomatosa) leads to a higher degree of articular alteration than a pure "small-intestine Crohn" (= ileitis terminalis). The joints preferentially affected are in the region of the lower extremities (knee and ankle joints). Concomitant Bekhterev's disease (spondylitiis ankylopoietica) is found in 7-10% of cases. Osteomyelitis represents a rare and serious complication: it can appear in the course of chronic Chron's disease (mainly with intestinal fistulas), especially in the region of the pelvic bones. Further aspects of interest from an orthopedic viewpoint are hypertrophic osteoarthropathy with periossal neoformation, granulomatous changes in the bone itself, and aseptic osteonecrosis. PMID- 2094209 TI - [Myelography, computerized tomography and electromyography in intervertebral disk diseases of the lumbar spine]. AB - Fifty-five patients who underwent lower spine surgery were preoperatively evaluated with myelography and postmyelography CT. ENMG was done on 23 patients. CT had the highest accuracy in finding the affected level (F = 75,5; p less than 0,0005) as compared to myelography (F = 46,5; p less than 0,0005) or to ENMG (F = 11,4; p greater than 0,15). We did not find statistical differences in diagnostic accuracy in different disc spaces nor was there a difference between primary and recurrent low-back disease. PMID- 2094210 TI - [Experience with open meniscus refixation. Results of follow-up in 17 cases]. AB - Results of refixation in 17 cases of meniscus ruptures are presented. The operation was an open arthrotomy. The follow-up examination is described. There are found 7 very good, 7 good and 3 satisfactory results. These results allow the attempt to preserve meniscus under certain preconditions by means of suture. PMID- 2094211 TI - [Errors and dangers in surgical traumatology with special reference to surgical tactics and technique]. AB - In one hospital the operative treatment of fractures within ten years had been critically analysed. The established mistakes and risks unambiguously show reserves for the improvement of the results in the treatment. Despite the avoidable operational-tactic and -technic mistakes the result of the medical attendance often ist negative. PMID- 2094212 TI - One-stage hip reconstruction with Dega's transiliacal osteotomy in the treatment of congenital hip dislocation in children. AB - Results of surgical treatment of the congenital dislocation of the hip in 40 children (2-5 years) are presented. The mean observation period was 8 years. 80% of very good and good results were obtained in the included material. One-stage hip reposition -reconstruction with Dega's transiliacal osteotomy, applied to children of 2-3 years, gives positive results, adding to further development of the hip joint. PMID- 2094213 TI - [Retrospective analysis of hip joint development after pericapsular Pemberton ilium osteotomy (modified by Tonnis) in conjunction with intertrochanteric corrective osteotomy]. AB - A review of 45 hips with disorders (congenital dislocation of the hip, subluxation of the hip, hip dysplasia with or without secondary pertheslike changes) treated by pembertons pelvic osteotomy with femur osteotomy is shown. Its a followed-up about two years. Many of them (85%) had satisfactory roentgenographic results and its showed the effectiveness of this procedure. We think the best time for treatment is the age between 2 and 4 years. PMID- 2094214 TI - [A new prosthetic smooth wall shaft]. AB - A report about our productions and experiences with the smooth wall of the body's bed from Polyurethanschaum EZ 7607 system. The material mark out trough permanent improvement of it's wear and economical properties. Recently useful technique will be further developed trough continuous improvements of the materials in addition to our experiences. PMID- 2094215 TI - Sequence differences in introns flanking exon 48 of the dystrophin gene. PMID- 2094216 TI - Enrichment of gamma/delta T cells in peripheral blood lymphocytes activated with interleukin-2. AB - Human peripheral blood lymphocytes cultured with 1000 U/ml recombinant (r) IL-2 were quantitatively analyzed for gamma/delta T cells relative to their very low levels in fresh blood. For this purpose the moAB TCR delta 1 recognizing the delta chain of TCR 1 was used. In addition IL-2 activated lymphocytes were tested for their antitumour cytotoxicity and their cytotoxic activity against autologous and allogeneic lymphocytes. The results show a significant increase in gamma/delta T cells of up to 35% in human lymphocytes cultured for 20 days with 1000 U/ml rIL-2. This increase of gamma/delta T cells was associated with the appearance of cytotoxic activity against autologous and allogeneic lymphocytes. It seems reasonable that gamma/delta T cells might be responsible for autologous cytotoxicity of long term cultured IL-2 activated lymphocytes. When sorting fresh blood lymphocytes for Leu 19+ and Leu 19- before IL-2 activation, enrichment of gamma/delta T cells could be demonstrated in both subpopulations after 20 days of culture. The question arises whether gamma/delta T cells have any functional significance in IL-2 activated lymphocytes. PMID- 2094217 TI - [Characterization of surface fluorescence signals of isolated perfused rat kidney]. AB - The NAD(P)H- and flavoprotein fluorescence signals of the isolated perfused rat kidney were characterized by their electrochemical properties and by comparing them with those of isolated kidney cortex mitochondria. From titration experiments with lactate pyruvate under anoxic conditions it is concluded that about 25% of the NAD(P)H-fluorescence can be attributed to the cytosolic pyridine nucleotides. For this signal a midpoint potential of -268 mV was calculated. The major part of the NAD(P)H-fluorescence signal was of mitochondrial origin, showing a midpoint potential of -304 mV which was titrated with beta hydroxybutyrate/acetoacetate. A comparable value (Em7.4 = -310 mV) was found for isolated kidney cortex mitochondria using the same redox couple. The flavoprotein fluorescence could be totally attributed to the mitochondrial compartment and was found to originate from the NAD-dependent alpha-lipoamide dehydrogenase and the electron transfer flavoprotein of beta-oxidation to approx. 60% and 40%, respectively. A midpoint potential of -285 mV was determined for the NAD dependent part of the flavoprotein signal. On the basis of these results it can be concluded that the fluorescence changes which were caused by ouabain in the normoxically perfused rat kidney reflect an increase in reduction of the mitochondrial NAD-system. PMID- 2094218 TI - Interactions between group B streptococci and human cord blood lymphocytes. AB - Group B streptococci (Streptococcus agalactiae) of various serotypes (Ib/c, III/x, III/R, and B variant) and different sources of isolation were analyzed for their to interact with human mononuclear cells (MNC). Type I streptococci were obtained from a neonate dead of an invasive group B streptococcal infection. Examining the attachment of these bacteria to human peripheral lymphocytes and their ability to influence the proliferation of cultured adult and neonatal MNC, the following results were obtained: (1) Type Ib/c, III/x, and B variant strains adhered spontaneously to neonatal cord blood lymphocytes. The bacteria were bound by large lymphoid cells not detectable in the peripheral blood of adults. (2) Addition of group B streptococci to neonatal MNC cultures increased lymphocyte proliferation approximately 8 fold (n = 32) above the background. The reactivity of neonatal lymphocytes was highly reproducible with a mean peak proliferation close to day 5 of culture and a ratio of 60 CFU MNC. The control cell proliferation induced by Pokeweed mitogen (2 micrograms/ml) gave a mean stimulation index of 58. In contrast to cord blood cells, adult MNC responded only slightly with either proliferation of streptococcal binding. Clinical type I strain induced mean peak [3H]thymidine incorporation into neonatal MNC was approximately 16 times higher than into that of adults. Streptococcal adherence and lymphocyte activation did not depend on serotype specificity and clinical origin of the strains investigated. Therefore, the ability to interact with human cord blood lymphocytes seems to be a common property of group B streptococci. PMID- 2094219 TI - A combined adenine-phosphate effect inhibits the reactivation of eye lens epithelial cells in primary culture. AB - A low molecular weight component from serum, which in combination with adenine strongly retards the spreading of lens epithelial cells in primary culture, could be identified as inorganic phosphate. The possible mechanism of the combined action of adenine and phosphate is discussed. PMID- 2094220 TI - Acoustically evoked potentials of the basal forebrain and the nucleus cuneiformis of the freely moving rat. AB - Acoustically evoked potentials (AEP) were recorded and analysed in the basal forebrain (bf, nucleus basalis magnocellularis) and in the mesencephalic parabrachial nucleus cuneiformis (Cnf) of freely moving rats and the modulatory effects of electrical single stimulations within both cholinergic regions on these AEP are described. Bipolar electrodes were implanted in both regions for stimulation and AEP recording. Electrical single impulses with increasing intensities were applied 100 ms before or simultaneously with the clicks. The AEP of the bf as well as the Cnf varied their configuration in dependence on the behavioural state. During grooming, amplitude reductions of certain components of both AEP were found in in comparison to relaxed wakefulness. Electrical stimulation of the bf had no effect on the early component of the Cnf-AEP, which is likely generated within the Cnf. However, a later component of the Cnf-AEP whose generation locus within the mesencephalon is unknown was modulated by bf stimulation. This indicates that the bf is only able to modulate secondary acoustic information processing in the mesencephalon. Cnf stimulation caused reductions of the amplitudes and of the peak times of the bf-AEP. This modulation of the bf-AEP takes place likely within the acoustic pathway. PMID- 2094221 TI - Hormonal and renal responses to arterial chemoreceptor stimulation by almitrine in healthy and normotensive men. AB - Healthy and normotensive men (n = 11) were hospitalized and kept under controlled fluid and sodium intake (120 mequ/d) for 5 days. Their systemic arterial blood pressures as well as heart and breathing rates were measured, and venous blood and urine samples were collected at intervals of 1-4 h. Diuresis was induced by scheduled drinking of tea (150 ml/h). Electrolytes, osmolality, and creatinine were determined in both plasma and urine samples. Aldosterone, cortisol, and vasopressin concentrations were measured only in the plasma. On the 2nd and 3rd day of the experiments the participants received orally either a placebo-pill or 100 mg almitrine bismesylate (Vectarion). Each subject was tested in a placebo- and an almitrine experiment. The subjects responded to the almitrine treatment with a suppression of the plasma aldosterone content, a transient rise of glomerular filtration rate, a natriuresis and an increase of renal concentrating ability. In the placebo-experiments, only the transient rise of filtration rate was significant. The data indicate that almitrine, by stimulating the peripheral arterial chemoreceptors, suppresses plasma aldosterone and inhibits renal proximal sodium reabsorption by so far unknown mechanisms. They also suggest that oral and intravenous almitrine administrations, respectively, might differently affect renal hemodynamics and excretory function. PMID- 2094222 TI - Correlation of photically evoked afterdischarge parameters to the respiration rate and their modulation by basal forebrain and nucleus cuneiformis stimulation in the freely moving rat. AB - On 29 freely moving Long-Evans rats the correlations of various parameters of photically evoked afterdischarges (PhAD) with respiration rate were observed and statistically evaluated. Increasing respiration rate is related with PhAD of reduced amplitude, higher number per flash and increased frequency. PhAD show their best appearance at frequencies around 6.2 PhAD/s. At frequencies below 5.9 and above 6.4/s PhAD number and amplitude decreased. Electrical single impulse stimulation of the nucleus cuneiformis (Cnf) decreased PhAD trigger rate significantly stronger than basal forebrain (Bf) stimulation from 10 rats. The Cnf stimulation effects on PhAD continued longer than Bf stimulation effects which is also recognizable on the different modulations of the PhAD amplitude and frequency. After the desynchronizing stimulation effects, more synchronized PhAD were found, which indicates a desynchronization-synchronization sequence of the PhAD modulation after Bf and Cnf stimulation. PMID- 2094223 TI - [Influence of dopamine administration of peripheral triiodothyronine production]. PMID- 2094224 TI - Effect of testosterone on the glycosphingolipid composition of the rat kidney. AB - A series of experiments was conducted to examine the effect of subcutaneous administration of synthetic testosterone (500 micrograms/100 g body weight) on the acidic and neutral glycolipids. The kidney glycosphingolipids were separated by using Sep-Pak cartridge column. Florisil column, and high performance thin layer chromatography, and analyzed by gas liquid chromatography. Testosterone administration increased the total content of ceramide, acidic and neutral glycolipids. The increase in total neutral glycolipids was mainly due to an increase in glucosyl- and globotetraosylceramide. The increase in total gangliosides was due to the increase in GM3 (hematoside) and "others". The relative percentage of N-glycolylneuraminic acid in GM3 was increased whereas the relative percentage of sphingoside and phytosphingosine were increased and decreased, respectively, in GM3, glucosyl- and globotetraosylceramide. The relative percentage and chain length of hydroxy and nonhydroxy fatty acids of major glycosphingolipids were altered in this organ. PMID- 2094225 TI - Muscle elasticity: effect of muscle length and temperature. AB - The present study describes a new method which allows the determination of muscle elasticity by applying quick releases at one end of a muscle and measuring the resulting tension drops at both ends, and simultaneously the propagation time of the mechanical impulse. The elasticity determined by both methods was examined on resting as well as on tetanized frog muscles (Rana esculenta, M. flexor hallucis brevis) in relation to muscle length and at two different temperatures 1 degree C and 20 degrees C. The average propagation velocity of the mechanical impulse of resting muscle was 55.7 +/- 4.7 m/s and of the contracting muscle 104.8 +/- 24.7 m/s at 1 degree C (L0, n = 6), which corresponds to elasticities of 3.3 +/- 0.5 N/mm2 and 14.4 +/- 6.2 N/mm2, respectively. The elasticity modulus calculated from the tension drop was for the resting muscle 2.3 +/- 0.5 N/mm2 and for the contracting muscle 11.1 +/- 2.1 N/mm2 (L0, 1 degree C, n = 6). When the muscle length is varied, the elasticity modulus corresponds to the length-tension relation of the resting and the isometrically contracting muscle. There is a strong correlation between the elasticity moduli which was determined by both methods for measurement of resting (r = 0.99, n = 19, p less than 0.05) and contracting muscle (r = 0.97, n = 19, p less than 0.05). This relation between elasticity and tetanic tension, i.e. filament overlap at constant temperature, can be interpreted in accordance with the sliding filament theory. But if the temperature is increased from 1 degree C to 20 degrees C, an increase of the tetanic tension (Q10 = 1.56) and a decrease of the elasticity measured by both methods (Q10 of 0.86 and 0.84) were obtained. This suggests that the increased tetanic force is generated by a smaller number of attached cross-bridges, but with a higher amount of force generated by each cross-bridge. PMID- 2094226 TI - Insulin stimulates postnatal development of renal tubular transport of p aminohippurate. AB - The influence of repeated administration of insulin on renal tubular transport of PAH was investigated. There was a stimulating effect in young rats with an immature kidney function. The distinctly higher degree of accumulation in renal cortical slices is in accordance with the enhanced PAH excretion in 10- and 20 day-old animals. PMID- 2094227 TI - Congenital absence of the oval window. AB - From 1983 to 1987, seven patients with conductive hearing loss were found to have congenital absence of the oval window. Six of these patients underwent vestibulotomies and reconstruction with House wires or total ossicular reconstruction prostheses. Surgical findings included absent or rudimentary stapes in all cases, abnormal facial nerves in four cases, and abnormal long processes of the incus in four cases. All patients had normal external ear canals and tympanic membranes. Hearing initially improved 20 to 45 dB in four of the six patients reconstructed. Over time, however, much of this initial hearing gain was lost. A marked difference in hearing results was evident between this series of absent oval window cases and a recent series of major atresia cases. PMID- 2094228 TI - Severe frostbite of the upper extremities--a psychosocial problem mostly associated with alcohol abuse. AB - In the catchment area of Helsinki University Central Hospital (in total 16 surgical hospitals) amputation was performed on 9 patients with frostbite in the upper extremities during 1984-1985. The population during the study period in this area was 1.165,000 inhabitants, corresponding to 24% of the whole population in Finland. All 9 patients were male and the mean age was 49 years (range 31-75). All amputations performed were of the fingers, the third, fourth and fifth fingers most frequently affected. Alcohol was a marked etiologic or contributing factor in most of the frostbites. Two patients were chronic schizophrenics showing no signs of alcohol abuse, but the remaining 7 were either acutely or chronically alcohol intoxicated: 5 patients were chronic alcoholics, one was an alcohol abuser without a definite diagnosis of alcoholism, and one patient with no previous history of alcohol abuse was alcohol intoxicated. Based on the present study it is clear that, in addition to the cold winters in Finland, other factors contribute to severe frostbite. These include many psychosocial factors such as alcoholism or mental disease, unbalanced marital status, occupation handicap and lack of regular residence. PMID- 2094229 TI - Detecting health fraud in the field of learning disabilities. AB - Quackery is currently a widespread problem that pervades all aspects of healthcare, including the treatment of learning disorders. A discussion of the nature of modern health fraud in special education is presented. The psychopathology of health fraud, the standards by which pseudoscience and health quackery are defined, and the complexities of learning disorders are discussed. A Therapy Rating Scale to determine if an alternative therapy is reasonable is presented. Several popular therapies are used as examples. PMID- 2094230 TI - Management of autonomic dysfunction in severe tetanus: the use of magnesium sulphate and clonidine. AB - The treatment of severe tetanus with autonomic dysfunction is discussed, with emphasis on the use of magnesium sulphate. An exemplary case is reported, describing the inadequate response to magnesium, but the previously unreported and successful use of clonidine to control sympathetic overactivity. The properties of clonidine are reviewed. Clonidine is felt to be a logical and appropriate drug for the treatment of autonomic dysfunction in severe tetanus. PMID- 2094231 TI - Brucellosis: a rare cause of the unstable spine. AB - Brucellosis infection in humans is very rare in the United States. Occasional cases are identified primarily in individuals who have been exposed to an animal's raw dairy products. Presented is a rare case of human brucellosis involving the cervical spine. Of interest is how the case unfolds, reminding the practitioner of the need for thorough clinical practice. A review of clinical features and findings is offered. PMID- 2094232 TI - Lumbo-sacral adhesive arachnoiditis: a review. PMID- 2094233 TI - Treatment of hyperprolactinemia in major depression. PMID- 2094234 TI - Shelterization: how the homeless adapt to shelter living. AB - Emergency shelters have become the backbone of the service delivery system to the homeless. Particularly in large shelters, crime is a pervasive aspect of life. But despite the dangers of shelter living, many residents do not flee; instead they develop coping strategies that provide them with a feeling of mastery unparalleled on the outside. This adaptation process, which the authors call "shelterization," is characterized by a decrease in interpersonal responsiveness, a neglect of personal hygiene, increasing passivity, and increasing dependency on others. The authors suggest that the shelterization process may be ameliorated by helping homeless persons establish positive social networks and affiliations with social service and mental health providers. They believe onsite psychosocial rehabilitation programs can foster such affiliation by offering a therapeutic alternative to the shelter subculture. PMID- 2094235 TI - Screening hospital admissions from the emergency department for occult carbon monoxide poisoning. AB - Because cases of unrecognized carbon monoxide (CO) poisoning have been described among patients admitted to the hospital with other diagnoses, screening hospital admissions with carboxyhemoglobin testing has the potential for preventing morbidity among patients as well as among their cohabitants. Carboxyhemoglobin levels were obtained on 753 patients admitted to the hospital from the emergency department over a 3-month period during the winter. Patients in whom CO poisoning was diagnosed in the emergency department prior to admission were excluded. The mean carboxyhemoglobin level was 2.52% +/- 1.85%; there was no significant difference in mean carboxyhemoglobin among patients with medical, surgical, neurological, and psychiatric admission diagnoses (F = 1.17; df = 3,746; P = .32). Two patients (0.3%; 95% confidence limits, 0.04% to 1.1%) from the entire admission cohort, and one of 20 patients (5%; 95% confidence limits, 0.3% to 26.9%) admitted with seizures, had carboxyhemoglobin levels greater than 10%. The carboxyhemoglobin levels of the two patients were only marginally elevated, with levels of 10.9% and 11.3%. The cost of the carboxyhemoglobin screening program was $2.26 per patient result, or approximately $2,100 over a 3-month winter heating season. A program for screening emergency department admissions with carboxyhemoglobin testing, although feasible in terms of cost, detected few cases of unrecognized CO poisoning. PMID- 2094236 TI - Van Gogh had Meniere's disease and not epilepsy. AB - We intend to correct the historical error that Vincent Van Gogh's medical problems resulted from epilepsy plus madness, a diagnosis made during his life but for which no rigid criteria are apparent. Review of 796 personal letters to family and friends written between 1884 and his suicide in 1890 reveals a man constantly in control of his reason and suffering from severe repeated attacks of disabling vertigo, not a seizure disorder. His own diagnosis of epilepsy was made from the written diagnosis by Dr Peyron, the physician at the asylum of St Remy (France), wherein on May 9, 1889, Van Gogh voluntarily committed himself to the asylum for epileptics and lunatics. However, the clinical descriptions in his letters are those of a person suffering from Meniere's disease, not epilepsy. The authors point out that Prosper Meniere's description of his syndrome (an inner ear disorder) was not well known when Van Gogh died and that it often was misdiagnosed as epilepsy well into the 20th century. PMID- 2094237 TI - Concerns about contagious disease prompt infection controls for CPR. PMID- 2094238 TI - Viral infections during pregnancy: a guide for the emergency physician. AB - Emergency physicians are frequently called on to treat or advise pregnant patients. When faced with a pregnant patient who has clinical evidence of or exposure to a viral illness, the emergency physician must be aware of the potential maternal and fetal risks posed by various viral agents. This review provides current, accurate information and guidance for the pregnant patient. PMID- 2094239 TI - Emergency alarms. PMID- 2094240 TI - Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression. AB - Two patients with sideroblastic anemia secondary to zinc-induced copper deficiency absorbed excess zinc secondary to oral ingestion. The source of excess zinc was a zinc supplement in one case; in the other, ingested coins. In each case, the sideroblastic anemia was corrected promptly after removal of the source of excess zinc. These two cases emphasize the importance of recognizing this clinical entity, since the myelodysplastic features are completely reversible. PMID- 2094241 TI - A piece of my mind. Stein-Bockenheim. PMID- 2094242 TI - Moral endorsement of passive voluntary euthanasia must also apply to active. PMID- 2094243 TI - Epidemiological abuse. PMID- 2094245 TI - Health-risk appraisal sound tool for developing healthcare strategy. PMID- 2094244 TI - Chlorophenol degradation coupled to sulfate reduction. AB - We studied chlorophenol degradation under sulfate-reducing conditions with an estuarine sediment inoculum. These cultures degraded 0.1 mM 2-, 3-, and 4 chlorophenol and 2,4-dichlorophenol within 120 to 220 days, but after refeeding with chlorophenols degradation took place in 40 days or less. Further refeeding greatly enhanced the rate of degradation. Sulfate consumption by the cultures corresponded to the stoichiometric values expected for complete oxidation of the chlorophenol to CO2. Formation of sulfide from sulfate was confirmed with a radiotracer technique. No methane was formed, verifying that sulfate reduction was the electron sink. Addition of molybdate, a specific inhibitor of sulfate reduction, inhibited chlorophenol degradation completely. These results indicate that the chlorophenols were mineralized under sulfidogenic conditions and that substrate oxidation was coupled to sulfate reduction. In acclimated cultures the three monochlorophenol isomers and 2,4-dichlorophenol were degraded at rates of 8 to 37 mumol liter-1 day-1. The relative rates of degradation were 4-chlorophenol greater than 3-chlorophenol greater than 2-chlorophenol, 2,4-dichlorophenol. Sulfidogenic cultures initiated with biomass from an anaerobic bioreactor used in treatment of pulp-bleaching effluents dechlorinated 2,4-dichlorophenol to 4 chlorophenol, which persisted, whereas 2,6-dichlorophenol was sequentially dechlorinated first to 2-chlorophenol and then to phenol. PMID- 2094246 TI - JPAC quotas: time to reassess roles. PMID- 2094247 TI - Premenstrual syndrome. PMID- 2094248 TI - Cutaneous reactions to diltiazem. PMID- 2094249 TI - Flumazenil in routine upper gastrointestinal endoscopy. PMID- 2094250 TI - Unraveling the migraine mystery. PMID- 2094251 TI - Student selection: time to reconsider? AB - The fate of most aspiring veterinary surgeons is determined not by their professional examinations but by their A-level results. Anything less than two As and a B and the outlook is bleak, though not irretrievable. In this article, Dr Robert Michell examines the system by which students are selected, and suggests that the system is ripe for re-evaluation. PMID- 2094252 TI - Quality assurance in private veterinary laboratories. PMID- 2094253 TI - Abdominal trauma. PMID- 2094254 TI - Pulse treatment with methylprednisolone in rheumatoid arthritis. PMID- 2094255 TI - Surgery and the elderly. PMID- 2094256 TI - Lumbo-sacral adhesive arachnoiditis. PMID- 2094257 TI - Diagnostic value of adenosine deaminase activity in tuberculous effusions. PMID- 2094258 TI - [Current problems in lipomas of the oral mucosa with reference to our experience of 7 cases]. AB - We present a review of the lipomas in the buccal mucosa in relation with our experience in seven cases. PMID- 2094259 TI - [Sialoadenosis of the parotid glands: diagnostic considerations]. AB - We present 3 cases of Sialoadenosis of the parotid glands, one male and two females, who presented associated systemic pathology (liver cirrhosis and diabetes mellitus), detected following clinically suspect syaloadenosis (the patients were unaware of their systemic disease). In all three cases definitive diagnosis was established by needle aspiration of the gland. Which revealed great acinar dilatation. Finally, differential diagnosis was established between sialoadenosis and those conditions with clinical presentations similar to those described for sialoadenosis. PMID- 2094260 TI - [Clinico-pathological study of oral mucoceles]. AB - We present a clinical and histopathological study of 25 mucoceles of the oral cavity. Incidence was found to be greatest between age 10 and 20 (12 cases), with no significant differences in terms of sex. The lower lip was most frequently affected (17 cases), other locations being much less common. In 72% of cases there were etiological antecedents of traumatism. Mucocele size varied from 3 to 13 mm. although a great many of them were between 10 and 13 mm. Evolution period was 1-16 months, incidence being highest between 1 and 4 months. Finally, histology showed 95% to be due extravasation, the remaining 5% being the result of retention. Among the extravasation mucoceles, 11.7% were in the initial phase, another 11.7% in the reabsorption stage, and 76.4% in the final phase. PMID- 2094261 TI - [Xerostomia]. AB - A great many conditions may lead to dry mouth; indeed, xerostomy is a very frequent clinical finding that occasionally does not receive the attention deserved. A review of this condition is carried out, providing a practical perspective for the general stomatologist regarding the physiopatological mechanisms involved, the clinical manifestations, diagnostic procedures and current therapeutic approaches. PMID- 2094262 TI - [Medicated iontophoresis]. PMID- 2094263 TI - [Class III. Current criteria for diagnosis and treatment. 2]. PMID- 2094264 TI - [Osseointegration of IMZ implants. Ultrastructural analysis of a case]. AB - A study with scanning electron microscope of an osseointegrated titanium implants (IMZ) was performed, analyzing the characteristics of the interface bone- titanium oxid. It was observed that the characteristics of the interface were similar to the ones shown by other devices whose design is different (Branemark system). The present study confirms that an adequate surgical technique and a satisfactory post-operation on phase (in which the implant is free of load) lead to the osseointegration of the implant; this facts is proved by the absence of mobility of the device, and also by structural findings typical of normal osseous tissue. PMID- 2094266 TI - [Saliva and caries]. PMID- 2094265 TI - [Diagnosis of compound odontoma. Apropos of 2 cases]. AB - We have a bibliografical study of the composite odontomas from the diagnostical point of view. We will present two clinical cases. Once the medical revision is done, and the tumor is localized, we analyze lesions associated with the tumor and compare the diagnostic from the clinical point of view as well as the radiografical point of view. PMID- 2094268 TI - [Immediate denture]. PMID- 2094267 TI - [Ionomer as a substitute for lost dentin in conservative dentistry]. AB - The availability of glass Ionomer cement with physical properties, very similar to dentin given the clinician a substitute for dentine (it is artificial dentin) which has had to be eliminated because of caries. Its use in restaurative dentistry with silver amalgam allows us to reduce the size of cavity without having to eliminate all the enamel which is not supported by dentine (we can leave hollowed enamel which will be supported by the glass Ionomer cement as it acts as dentine). Using it in restaurative dentistry with composite resins offers us an adherent base stuck chemically to the dentine, which is of similar colour, with the rest of the dental structure. It also avoids recurrent caries as it contains fluoride ions, and provides a strong micromechanic union with the composite (more similar in colour and more resistant) which is placed onto the surface. PMID- 2094269 TI - [Arthroscopy of the temporomandibular joint. A study of 20 patients]. AB - Temporomandibular joint arthoscopy is a new diagnostic and therapeutic modality and its development is in its infancy. The purpose of this article is to describe arthroscopic pathologic findings of the superior joint space. PMID- 2094270 TI - [Fibronectin as an inductor of new attachment. 1]. PMID- 2094271 TI - Biotechnology-based methods for the detection, enumeration and epidemiology of food poisoning and spoilage organisms. PMID- 2094272 TI - Delivery of recombinant peptide and protein drugs. PMID- 2094273 TI - Liposomes in vivo: prospects for liposome-based pharmaceuticals in the 1990s. PMID- 2094274 TI - Sieving by agarose gels and its use during pulsed-field electrophoresis. PMID- 2094275 TI - Biotechnology of vaccine development. PMID- 2094276 TI - Immunological approaches for manipulation of animal growth, body composition and fecundity. AB - The ability to manipulate certain physiological processes by using the immune system, so as to regulate endocrine secretions and/or actions is clearly possible. The dramatic effects of immunocastration and the ability to increase ovulation rates in sheep are probably the best examples. Other approaches along similar lines have produced equivocal results, the effects of immunization against somatostatin being the most notable case. Although anti-idiotypic antibody approaches to producing hormone mimics have also been shown to be attainable and, indeed, possibly involved in certain auto-immune dysfunctions of the endocrine system, to date no successful applications of this approach have been demonstrated in commercial livestock. The ability to enhance hormone action using antibodies is an extremely promising area. Its prospects probably hinge on the ability to synthesize suitable short peptides which will mimic epitopes on the hormone and so permit the development of active immunization techniques to produce polyclonal antibodies of restricted and enhancing specificity. It seems less likely that administration of hormones pre-complexed to monoclonal antibodies has any potential as a practical approach to manipulating animal productivity. All of these approaches involving active immunization suffer the same limitations: the highly variable response of individual animals and the general inability to regulate the duration of the response; a need to find suitable adjuvants to replace the almost universally used and commercially unacceptable Freund's adjuvant; and the problem of trying to generate what, in most cases, is an auto-immune response. A second group of approaches consists of attempts to use antibodies in their classical role, that is by targeting antigens or cells for destruction by the immune system. These include, for example, antibodies directed against adipose tissue or cytotoxic antibodies to specific hormones aimed at destruction of the hormone-secreting cells. Since these are passive immunization techniques, the antibodies can be assessed carefully in vitro and administered in appropriate doses. However, success in these applications is largely dependent on the inability of damaged tissues to regenerate, since retreatment is generally precluded because of the anti immunoglobulin response induced in treated animals. Toleragenic forms of such antibodies or the use of appropriate immunosuppressants may ultimately remove this limitation. Perhaps the greatest current limitation to the use of all of these techniques in animal production systems, however, is public resistance to the use of such techniques.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2094278 TI - [Removable partial denture principles applied to indirect bonded fixed partial denture in posterior teeth]. AB - The authors present a clinical case of adhesive prosthesis on posterior teeth, where it is proposed an alternative technique based upon the retentive principles of removable parcial prosthesis, diminishing the elimination of enamel. PMID- 2094277 TI - [Restorative dentistry in a community center. 10-year report]. AB - It is reported the results of voluntary odontological assistance in the Community Center of the Methodist Church of Vila Virginia. In a period of ten years the relation patient/dentistry student was an average of 23.08. Of the procedures, 69.9 per cent were amalgam restaurations and 30.1 per cent with silicate cement or resin. This is an important extracurricular activity for the student, in the sense that it helps improve his techniques. On the other hand, although restricted in time, this work has been important for the oral health of the community. Uniterms: voluntary extracurricular activity; amalgam, silicate or resin restaurations. PMID- 2094279 TI - [Healing of zygomatic arch fractures in rats with lesions of the median hypothalamic eminence]. AB - The purpose of this study was to verify the effect of hypothalamic median eminence lesion on healing process in fracture of anterior portion of zygomatic arch, in rats, by histologic evaluation. The animals were killed in number of 5 for each periods at 6, 12, 24 and 36 days post-lesion. Our results showed morphologic changes and tinctorial in all considered periods, with more evidence at 12 and 24 days post-fracture and evidents signals of hipomineralization. This disfunction appeared only after a mean period of 12 days post-lesion. PMID- 2094280 TI - [Parendodontal surgery of the lower third molar: report of a clinical case]. AB - The parendodontic surgery intends to the resolution of accidental or pathological condition that can't be recoverable by usual endodontic treatment. In this case, the authors present a clinical case where a apical curettage and apicectomy were done in a mandibular right third molar, to show the account of this procedure yet in the actual context. PMID- 2094281 TI - [Critical analysis of flap design in parendodontics]. PMID- 2094282 TI - [Fabrication of acrylic teeth for children's dentures]. AB - A simple technique to make children's prosthatic teeth with possibility of many sizes and form, stable shades, hard structure and fast work. PMID- 2094283 TI - Papers presented at the 6th International Symposium on Microbial Growth on C1 compounds. Gottingen, F.R.G., 20-25 August 1989. PMID- 2094284 TI - Structure/function relationships in methylotrophic yeasts. AB - This symposium marks the 15th anniversary of the discovery of microbodies in methylotrophic yeasts. In the intervening years much has been learned about the structure, function and biogenesis of these organelles and these advances are described. As our endeavours continued, unexpected results have confused commonly held views. This was for instance the case when microbody-minus mutants of yeasts became available which showed that some microbody matrix enzymes may be functional when present in the cytosol while others are not. At the molecular level, our understanding of structure/function relationships is also expanding. Examples are structural elements which relate to protein topogenesis and function of enzymes in different cell compartments. Other, perhaps more unusual, adaptations have also been encountered; some involve protein-protein interactions or even modified cofactors which possibly have helped methylotrophic yeasts to establish and/or maintain themselves in natural ecosystems. PMID- 2094285 TI - The cyanase operon and cyanate metabolism. AB - Cyanase is an inducible enzyme in E. coli that catalyzes bicarbonate-dependent decomposition of cyanate. It is encoded as part of an operon we have named the cyn operon, which includes three genes in the following order: cynT (cyanate permease), cynS (cyanase), and cynX (protein of unknown function). The direction of transcription is opposite to that of the lac operon, and the 3'-end of the cyn operon overlaps the 3'-end of the lac operon by 98 nucleotides. The gene cynR (regulatory protein) is located upstream from the cyn operon, and its transcription is opposite that of the cyn operon. The genes of the cyn operon and the cynR gene have been cloned, sequenced and over-expressed. Cyanate at concentrations of about 1 mM is toxic to strains of E. coli lacking the cyanase gene, but strains in which the inducible gene for cyanase is present can grow on cyanate as the sole source of nitrogen at concentrations as high as 20 mM. The presence of cyanase itself is not sufficient to overcome cyanate toxicity--the permease must also be present. Strains lacking the cyanase gene, but having a functional permease gene, are extremely sensitive to cyanate. Uptake of cyanate involves the product of the permease gene in an energy-dependent process. It appears that the cyn operon has evolved to function in detoxification/decomposition of cyanate arising from both intra- and extracellular sources. PMID- 2094286 TI - The growth rate-limiting reaction in methanol-assimilating yeasts. AB - The maximum growth rate of methylotrophic yeasts during growth on methanol is about 0.2 h-1. Since they are able to grow faster on substrates such as glucose we tried to identify the putative limiting step in methanol metabolism within the assimilatory pathway, leading to the formation of a major precursor for biosyntheses, or within the linear dissimilatory sequence. Growth experiments with mixed substrates and determination of some kinetic parameters allowed us to restrict the number of possible pacemaker enzymes. The dissimilatory sequence does not seem to be growth-rate limiting. This also applies to transketolase, transaldolase and fructose-1,6-bisphosphatase. Surprisingly, methanol oxidase appears to be the prime candidate. PMID- 2094287 TI - Biodegradation of low-molecular-weight halogenated hydrocarbons by methanotrophic bacteria. AB - Low-molecular-weight halogenated hydrocarbons are susceptible to degradation by anaerobic and aerobic bacteria. The methanotrophic bacterium Methylosinus trichosporium 0B3b degrades trichloroethylene more rapidly than other bacteria examined to date. Expression of soluble methane monooxygenase (MMO) is correlated with high rates of biodegradation. An analysis of 16 S rRNA sequences of 11 ribosomal RNAs from type I, type II and type X methanotrophs and methanol utilizing bacteria have revealed four clusters of phylogenetically related methylotrophs. This information may be useful for the identification and enumeration of methylotrophs in bioreactors and other environments during remediation of contaminated waters. PMID- 2094288 TI - Emerging applications of the methylotrophic yeasts. AB - The use of methylotrophic yeasts for the production of single-cell-protein (SCP), alcohol oxidase and fine chemicals has been proposed. Fermentation technology developed for the growth of these yeasts on methanol at high cell densities has been commercialized. However, it is the production of heterologous recombinant proteins by Pichia pastoris that is emerging as the most significant application of the methylotrophic yeasts. PMID- 2094289 TI - Chemistry of methylcorrinoids related to their roles in bacterial C1 metabolism. AB - Corrinoids are central cofactors in bacterial metabolism, where they participate in a series of organometallic and redoxprocesses. These depend on the unique coordination chemistry and reactivity of the corrin-bound cobalt centers to which, in the complete corrins, also a nucleotide function can coordinate intramolecularly. The roles of methylcorrinoids in bacterial C1 metabolism focus around the unusual Co-C-bond. PMID- 2094290 TI - Formate dehydrogenase. AB - Formate is a substrate, or product, of diverse reactions catalyzed by eukaryotic organisms, eubacteria, and archaebacteria. A survey of metabolic groups reveals that formate is a common growth substrate, especially among the anaerobic eubacteria and archaebacteria. Formate also functions as an accessory reductant for the utilization of more complex substrates, and an intermediate in energy conserving pathways. The diversity of reactions involving formate dehydrogenases is apparent in the structures of electron acceptors which include pyridine nucleotides, 5-deazaflavin, quinones, and ferredoxin. This diversity of electron acceptors is reflected in the composition of formate dehydrogenase. Studies on these enzymes have contributed to the biochemical and genetic understanding of selenium, molybdenum, tungsten, and iron in biology. The regulation of formate dehydrogenase synthesis serves as a model for understanding general principles of regulation in anaerobic organisms. PMID- 2094291 TI - Metabolism and energy generation in homoacetogenic clostridia. AB - Clostridium thermoautotrophicum and C. thermoaceticum contain an anaerobic electron transport chain. It involves hydrogen and carbon monoxide as electron donors and, presumably, methylenetetrahydrofolate as physiological electron acceptor. Cytochrome b554, cytochrome b559, menaquinone, a flavoprotein, ferredoxin and rubredoxin are parts of the electron transport chain. The electron transport results in the generation of a proton motive force which drives the synthesis of ATP or the uptake of amino acids. PMID- 2094293 TI - [Determination of kinesiographic parameters in phonation]. AB - We have registered mandibular movements produced during the reading of a text in spanish with a Sirognathograph in a random sample of 71 subjects, aged between 24 and 35, on the three planes of space. The obtained curves have allowed to measure 7 variables in order to define the characteristics of mandibular movements during speech. The results demonstrate that determinant planes for this purpose are sagittal and frontal. PMID- 2094292 TI - Molecular biology studies of the uptake hydrogenase of Rhodobacter capsulatus and Rhodocyclus gelatinosus. AB - In the photosynthetic bacteria, as in other N2-fixing bacteria, two main enzymes are involved in H2 metabolism: nitrogenase, which catalyses the photoproduction of H2, and a membrane-bound (NiFe) hydrogenase, which functions as an H2-uptake enzyme. The structural genes for Rhodobacter capsulatus and Rhodocyclus gelatinosus uptake hydrogenases were isolated and sequenced. They present the same organization, with the gene encoding the small subunit (hupS) (molecular masses 34.2 and 34.6 kDa, respectively) preceding the gene encoding the large one (hupL) (molecular masses 65.8 and 68.5 kDa, respectively). The two hupSL genes apparently belong to the same operon. The deduced protein sequences of the small and of the large subunits share nearly 80% and maximally 70% identity, respectively, with their counterparts in uptake hydrogenases found in N2-fixing bacteria. However, unlike in Bradyrhizobium japonicum, R. gelatinosus or Azotobacter chroococcum, another open reading frame (ORFX) was found downstream and contiguous to the R. capsulatus hupSL whose transcription seemed to depend on the same hup promoter as hupSL. ORFX contained 786 nucleotides capable of encoding a hydrophobic polypeptide of 262 amino acids (30.2 kDa). PMID- 2094294 TI - [Biomechanics of mandibular lateralization]. PMID- 2094295 TI - [Dental diseases in an excavated population in Fuente Hoz (Alava)]. PMID- 2094296 TI - [A design to improve ceramic stability]. PMID- 2094297 TI - [Preprosthetic periodontal treatment. What is its importance for the general dentist?]. PMID- 2094298 TI - On the controversies about clinical use of EEG brain mapping. AB - Quantitative EEG analysis, often called EEG Brain Mapping, consists of a large variety of separate techniques. Most of these techniques have demonstrated research uses, but few have been shown to have clinical applications that actually impact patient care. Substantial problems exist that can interfere with routine clinical applications. These include a variety of artifacts, confounding clinical problems, diversity of techniques and statistical issues. Existing medical literature suggests several areas where there are clinical uses at this time. EEG Brain Mapping can be used as a testing technique to determine abnormality and perhaps as a monitoring tool, too. It should be viewed as complementary to neuroimaging techniques, rather than a competitor. Those who introduce costly new technology bear the burden of proof for demonstrating its usefulness and cost-effectiveness. Evaluation of new tests should be based on several principles outlined here. EEG Brain Mapping, when used for clinical purposes, should be read together with the accompanying traditional polygraph EEG record. Reproducibility of results should be demonstrated, and artifacts, normal variants and other problems must be identified or avoided. The reader must recognize that features noted on statistical tests do not necessarily imply that pathology exists. Reporting results and clinical implications should be done carefully, thoroughly and with appropriate caution. Results are often quite nonspecific. The user must have skills, knowledge and abilities for reading polygraph EEG as well as additional experience and knowledge about quantitative EEG techniques and problems. Experts must remain careful and responsible about introducing EEG Brain Mapping into routine clinical practice. PMID- 2094299 TI - Evolution of neuromagnetic topographic mapping. AB - Magnetoencephalography has developed during the past twenty years with a different overall emphasis than found in electroencephalography. These differences are explored in selected applications. One dominant feature of magnetic studies is a quantitative approach to characterize the strength of neuronal activity, as well as its position within the brain. There is evidence from recent analyses of current source-density measurements in animal models that the deduced peak neuronal strength can also be interpreted in terms of the spatial extent of activity across cortex. PMID- 2094300 TI - EEG cartography before and after visual stimulation: a group study with descriptive non-parametric analysis of EEG data. AB - Ten right-handed students were submitted to a protocol of cognitive visual stimulations based on six successive sequences: EC1, EO, B1, B2, B3, EC2. Following a first "eyes closed" (EC1) multiple EEG recording (16 EEG leads, plus polygraphy), and an "eyes-open" recording (EO) with central visual fixation, 60 computer-controlled slides were presented successively for each of three successive recordings (B1, B2, B3) before the last "eyes-closed" recording (EC2). In B1, the subjects were asked to look at the meaningful black and white drawings presented without comment. In B2, a second set of similar pictures was presented, with the advice to try to remember later on the visually projected slides. In B3, a memory recognition task was introduced with 20 slides coming from the B1 set, 20 from the B2 set, completed by 20 new slides. Each slide was presented for 10.24s. followed by a beep audio-signal indicating that the subjects should press electronic mouse knobs alternatively in B1, B2, and for indicating their answers in B3. After artifact rejection, EEG spectral analysis was followed by parametrization and group studies applying Fisher non-parametric paired exact probability tests. Nine comparisons were computed: EC1-EC2, EC1-EO, EC2-EO, EO B1, EO-B2, EO-B3, B1-B2, B1-B3, B2-B3. A statistical strategy of descriptive inter-individual non-parametric. Fisher tests was undertaken, together with computation and mapping of averaged spectral parameter differences (mean amplitudes and frequencies, mean amplitudes %, resonance coefficients) for raw EEG, delta, theta, alpha, alpha 1, alpha 2, beta 1 and beta 2 frequency bands and probability maps.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094301 TI - Global field power and topographic similarity. AB - Multichannel recordings are commonly presented as topographic maps series displaying the change of the potential distribution over time. When reviewing a sequence of potential maps it becomes obvious that there are epochs with only little activity (few field lines; small extrema values) while at other times the fields display high peaks and deep troughs with steep gradients. The measure of global field power (GFP) corresponds to the spatial standard deviation, and it quantifies the amount of activity at each time point in the field considering the data from all recording electrodes simultaneously resulting in a reference independent descriptor of the potential field. Global field power is plotted as a function of time, and the occurrence times of GFP maxima are used to determine the latencies of evoked potential components. The topographical change occurring in subsequent potential field distributions may also be quantified by computing an index of global dissimilarity. Global field power and global dissimilarity show a complementary behavior over time: in general, high GFP is associated with similar fields while during periods between GFP peaks the topographic patterns of successive field distributions change rapidly accompanied by high dissimilarity values. The topographic changes, however, are best recognized by a segmentation procedure that considers field structure independent of GFP and global dissimilarity. The principles and practical applications of GFP computation, component latency determination and global dissimilarity of potential field distributions as well as a topographical time segmentation procedure will be illustrated with multichannel data evoked by visual stimuli. PMID- 2094302 TI - Do optimal dipoles obtained by the dipole tracing method always suggest true source locations? AB - Scalp potentials generated by a concentrated electric source in the brain are very similar to potentials generated by an electric dipole at the source position. In this sense a concentrated source in the brain is modelled as an electric dipole. When the source is diffuse such a dipole which best approximates the scalp potential is called an optimal dipole. Its position is calculated by the Dipole Tracing Method based on a realistic head model with homogeneous electric conductivity. There are 2 major difficulties inherent in this method: (1) The low electric conductivity of the skull causes systematic shifts of the optimal dipole positions from the true positions of concentrated sources; (2) the optimal dipoles cannot specify diffuse source positions. The first difficulty is overcome by using the numerical correction obtained by comparing the known dipole positions generated within a human head with their optimal ones. The second difficulty is removed to a certain extent by comparing the optimal dipole positions obtained with the 1-dipole and 2-dipole models together with their dipolarity. We have obtained criteria for the validity of the dipole approximation and source concentration. PMID- 2094303 TI - Modeling and source localization of MEG activities. AB - During the past decade, substantial advances in the understanding of the functional organization of the human brain have been made through the technique of MEG topographic mapping. Most of these investigations were concerned with the estimation and localization of sources which were modeled as single current dipoles positioned in a semi-infinite volume conductor with homogeneous conductivity. However, the sources in the brain are complex, and the head as a volume conductor consists of different materials with different electrical conductivities. The influence of these inhomogeneities on the MEG topography is studied by a computer simulation, modeling the sources as single or multiple dipoles located in inhomogeneous volume conductors. The computer simulation suggests some important aspects in estimation of source localization. The sources of MEG activities in human subject during sleep are also studied. A comparison of simulated MEG topographic patterns with measured data suggests that the sources of K-complexes can be modeled by two current dipoles. Sources for delta waves are analyzed by the FFT technique. The results show that the frequency distributions are different for delta waves measured by MEG and EEG techniques, leading us to conclude that at least two different sources are present. The MEG measurements have an advantage to provide important information concerning brain function which cannot be obtained using the EEG measurements. PMID- 2094304 TI - Clinical application of EEG topography in cerebral ischemia: detection of functional reversibility and hemodynamics. AB - To detect the functional reversibility and hemodynamic process in cerebral ischemia, the EEG topography cased on % time and amplitude was applied. % time and amplitude were obtained by the wave-form recognition method/EEGs were recorded under the resting state and during drug-induced conditions in 18 patients with steno-occlusion of main cerebral artery. The type of ischemic attack was TIA in 2 patients, RIND in 4, minor stroke in 7 and major stroke in 5. Six of 11 patients showed the improvement of EEG under induced hypertension. Four of those 6 patients were operated on ECIC bypass surgery, and all of them showed the improvement of clinical and EEG findings postoperatively. Twelve patients showed the deterioration of EEG under induced hypotension. Eight of them were operated on ECIC bypass surgery, and none of them suffered from reattack of cerebral ischemia postoperatively. Those preoperative EEG changes were observed mainly on the EEG topography of % time. And, the analysis of the EEG topography of % time under drug-induced conditions was available to study the pathophysiology of cerebral ischemia for selecting the suitable treatment. PMID- 2094305 TI - Speech perception and auditory P300 potentials after section of the posterior half of the truncus of the corpus callosum. AB - A 47 year old woman who underwent surgical section of the posterior half of the corpus callosum because of meningioma in the right lateral ventricle was studied from the aspects of speech perception and auditory evoked potentials. The pure tone audiometry showed normal hearing levels for both ears. The monosyllable perception test disclosed that the left ear had lower correct percent than the right ear. The dichotic listening test demonstrated remarkable extinction in response to verbal stimuli in the left ear. Auditory brainstem, middle latency and slow vertex responses were normal for both ears, without right and left difference. P300 event related potentials were recorded by three different pairs of stimuli: pure tone (1 KHz vs. 2 KHz), words (Aka vs. Kuro), and monosyllable (PA vs. BA). Both P300 for pure tone and word stimuli to each ear showed large positive potentials within 200-500 msec but P300 for monosyllable stimuli to each ear did not show obvious potentials within 200-500 msec. These results suggest that the posterior half of the truncus of the corpus callosum can be related to transfer of speech information between right and left hemispheres. PMID- 2094306 TI - Past, present and future of topographic mapping. AB - Traditional EEG and EP analysis is trace-oriented. When mapping became popular, results of waveform analysis were mapped. Increased exposure to brain field maps has begun to orient analysis to the spatial aspects. Different maps must be generated by different neuronal populations; this offers direct key to the analysis of higher brain function. Space-oriented data reduction selects maps with optimal signal/noise ratio using Global Dissimilarity index. Classification and statistics of map landscapes uses extracted descriptors (locations of extrema or centroids) or three-dimensional dipole models. Map classification leads to adaptive segmentation of evoked or spontaneous map series into functional micro states, the putative building blocks of perception and cognition. PMID- 2094307 TI - Theta rhythms: state of consciousness. AB - The role of midline frontal theta in human is discussed, with reference to its relation on consciousness. Clinical observations of the appearance of this theta activity under various conditions are reviewed. These include simulated diving, brain tumour, chemical intoxication, exercise, mental calculation, sleep and medication. The mechanism of generation of this frontal midline theta activity is discussed. PMID- 2094308 TI - Neurosurgical applications of topographic mapping. AB - Sophisticated spectral analysis and mapping of the EEG with computer techniques provides objective and reliable diagnostic information, which is superior to that obtained by naked-eye observation, even by experienced clinicians. In our department, a topographic system was introduced as one of major adjuncts to EEG examination in 1980, and we devised our own software (dynamic topography, compound dynamic topography, deviation ratio topography) to facilitate its clinical application. Topographic mapping is applied to assessment of the dominant hemisphere, evaluation after medical and surgical treatment, spatial localization of epileptic foci, and intraoperative monitoring for cerebral hypoperfusion. Besides these surgical applications, topographic analysis has contributed to human neurophysiology, for instance in determining the participation of the dentatethalamic tract in movement-related cortical potentials. Our experience of the neurosurgical and neurophysiological applications of topographic mapping will be presented. PMID- 2094309 TI - Spike voltage topography and equivalent dipole localization in complex partial epilepsy. AB - The EEG of 45 patients with complex partial epilepsy was recorded from standard and supplementary inferior temporal electrode sites for 2 or more days via cable telemetry onto video (VHS) tape (22-25 channels, common reference). Epochs with "temporal spikes" were read into a topographic EEG device where individual spikes were visually identified and averaged in sums of 8-32. Analysis of spike voltage topography revealed two distinct patterns - dipolar, Type 1 and non-dipolar, Type 2. One or the other spike type predominated in all but two patients. Application of source modeling techniques (3 shells, single dipole, 6 parameters) to the spike topography data revealed that both spike types had similar equivalent dipoles in terms of location and orientation, except for vector elevation. However, calculated dipoles for Type 1 spikes were more stable over the course of the spike peak. Correlations with clinical data and intracranial EEG suggest that Type 1 spikes originate in mesial temporal structures, while Type 2 spikes arise from temporal or frontal neocortex. Spike voltage topography and equivalent dipole localization appear to be useful in the presurgical evaluation of patients with focal epilepsy. PMID- 2094310 TI - Quantified neurophysiology with mapping: statistical inference, exploratory and confirmatory data analysis. AB - Topographic mapping of brain electrical activity has become a commonly used method in the clinical as well as research laboratory. To enhance analytic power and accuracy, mapping applications often involve statistical paradigms for the detection of abnormality or difference. Because mapping studies involve many measurements and variables, the appearance of a large data dimensionality may be created. If abnormality is sought by statistical mapping procedures and if the many variables are uncorrelated, certain positive findings could be attributable to chance. To protect against this undesirable possibility we advocate the replication of initial findings on independent data sets. Statistical difference attributable to chance will not replicate, whereas real difference will reproduce. Clinical studies must, therefore, provide for repeat measurements and research studies must involve analysis of second populations. Furthermore, Principal Components Analysis can be employed to demonstrate that variables derived from mapping studies are highly intercorrelated and data dimensionality substantially less than the total number of variables initially created. This reduces the likelihood of capitalization on chance. The need to constrain alpha levels is not necessary when dimensionality is low and/or a second data set is available. When only one data set is available in research applications, techniques such as the Bonferroni correction, the "leave-one-out" method, and Descriptive Data Analysis (DDA) are available. These techniques are discussed, clinical and research examples are given, and differences between Exploratory (EDA) and Confirmatory Data Analysis (EDA) are reviewed. PMID- 2094312 TI - Singular value decomposition--a general linear model for analysis of multivariate structure in the electroencephalogram. AB - The application of Singular Value Decomposition (SVD) to analysis of EEG and evoked potential data has led to a hypothesis concerning the underlying structure of the EEG recorded from multiple channels. Based on the SVD algorithm the EEG is considered to be the linear combination of a sufficient number of features, each of which is defined in terms of its spatial distribution, temporal distribution, and amplitude. Use of this model leads to clear concepts concerning sampling, data reduction, normalization, and calculation of statistical significance, some of which are less evident when analysis is restricted to a single domain of interest. PMID- 2094311 TI - Topographic analysis in brain mapping can be compromised by the average reference. AB - The average reference introduces ghost potential fields at the latencies for which the integral of scalp-recorded potentials differs from zero. These spurious effects occur because the average reference is computed from a limited number of (scalp) electrodes which do not survey the bottom half of the head. By arbitrarily re-setting the zero at each latency in the maps to be compared, it can also obliterate or even reverse topographical differences in the case of focal brain potentials enhancements thereby defeating the purpose of brain mapping. PMID- 2094313 TI - Clinical applications of auditory event related potentials in neurology. AB - Auditory ERP (AERP) studies have been performed in 56 patients with central nervous system disturbances. Forty seven patients (90.5%), had AERP component abnormalities concerning mainly P300 topography alterations and secondarily P300 latency prolongation. It is concluded that P300 is a very useful tool in clinical neurology and that P300 topography or latency alterations are not specific of any cerebral disturbance but can be found in any disease whenever cognitive functions are impaired. PMID- 2094314 TI - Beyond topographic mapping: towards functional-anatomical imaging with 124 channel EEGs and 3-D MRIs. AB - A functional-anatomical brain scanner that has a temporal resolution of less than a hundred milliseconds is needed to measure the neural substrate of higher cognitive functions in healthy people and neurological and psychiatric patients. Electrophysiological techniques have the requisite temporal resolution but their potential spatial resolution has been not realized. Here we briefly review progress in increasing the spatial detail of scalp-recorded EEGs and in registering this functional information with anatomical models of a person's brain. We describe methods and systems for 124-channel EEGs and magnetic resonance image (MRI) modeling, and present first results of the integration of equivalent-dipole EEG models of somatosensory stimulation with 3-D MRI brain models. PMID- 2094315 TI - EEG mapping for surgery of epilepsy. AB - This report describes the objectives, problems, and current techniques associated with using EEG maps in the management of surgery of epilepsy. The purpose of EEG mapping in epilepsy is to precisely identify and characterize epileptogenic zones of the brain. Such zones may be single or multiple, pointlike or diffuse, and may be near or distant from the recording electrodes. The resulting measured electric fields are used to obtain information which, when analyzed in light of all the complementary clinical information, can frequently help to localize and describe the epileptic foci with more precision. PMID- 2094316 TI - P3 topography in psychiatry and psychopharmacology. AB - Endogenous components of event related potentials are of particular interest in psychiatric diseases because of their relations to cognitive and behavioral processes. We studied the topography of these potentials in order to find out whether there are different scalp distributions in schizophrenic and depressive patients in relation to the psychopathological state and compared to normal controls. Furthermore variations of the topographical scalp distribution of P300 in normal volunteers after administration of physostigmine and biperiden was investigated. We demonstrated a clear relationship of the P300 amplitude with the negative symptom axis and found different topographical scalp distributions in different groups and experimental conditions. Topography of event related potentials is therefore a promising field of investigation for a better understanding of psychiatric disorders. PMID- 2094317 TI - Topographical display and interpretation of event-related desynchronization during a visual-verbal task. AB - Multichannel EEG recordings were performed during a visual-verbal judgement task with a verbal response using an event-related paradigm. EEG trials of 7 sec were first digitally band pass filtered (10-12 Hz, 10-11 Hz, 11-12 Hz), and the amplitudes were then squared and averaged over all trials. This processing method results in a time course of alpha power and allows us to quantify the event related desynchronization (ERD) in each EEG channel and to compute series of ERD maps in intervals of 125 msec. Analyzing the 10-11 Hz band, it was possible to study the time course and topographical pattern of cortical activation during visual encoding and cognition. Analysis of the 11-12 Hz band has enabled us, for the first time, to study the time course, spatial localization and extent of activation of speech, premotor and motor areas. We found that the speech centers were activated maximally 250 to 375 msec before speech onset and the SMA about 250 msec before speech onset. The results are preliminary, but demonstrate how much information can be extracted from the scalp EEG. PMID- 2094318 TI - Advances in neuromagnetic topography and source localization. AB - The development of ultra-low noise instrumentation for neuromagnetic mapping has yielded significant progress in the study of brain function and pathology. New multi-channel systems, belonging to an "intermediate" generation, are already in use, or are going to become operative in the near future. These systems permit simultaneous field mapping over a relatively large area of the scalp, and allow source localization on the basis of a single trial, although they still do not permit topographic mapping over the whole scalp. Significant improvements are being made also in realistic modeling of the human head and brain, with the aim at increasing the accuracy of source localization. Finally, a few examples of recent studies on normal brain function and application of the technique in the clinical field will be illustrated. PMID- 2094319 TI - Does heparin stimulate fibrinolysis? PMID- 2094320 TI - Interleukin-2 treatment-associated eosinophilia is mediated by interleukin-5 production. AB - During a trial using recombinant human interleukin-2 (rhIL-2) immunotherapy for acute myeloblastic leukaemia (AML) in remission, eosinophilia was observed in all patients. We used in-vitro clonogenic assays to investigate the mechanism of the eosinophilia in five patients. The mean eosinophil count increased from 0.05 x 10(9)/l before rhIL-2 to 0.98 x 10(9)/l within 48 h of stopping the infusion, and an exponential correlation between the pretreatment lymphocyte CD4:CD8 ratio and the maximum eosinophil count was observed. RhIL-2 did not stimulate eosinophil colony formation by normal bone marrow. However, serum collected from patients during rhIL-2 infusion was a potent stimulator of eosinophil colony forming units (CFU-Eo), but had no significant stimulatory effect on granulocyte-macrophage colony forming units (CFU-GM). The CFU-Eo stimulation by pre-treatment serum was 2.8-fold higher than control serum. Serum collected during treatment stimulated CFU-Eo 12 times more than control serum (P less than 0.05). By pre-incubating patient serum, collected during rhIL-2 treatment, with monoclonal antibodies to murine IL-5, or human granulocyte-macrophage colony stimulating factor (GM-CSF), a reduction of 80% and 38% respectively in eosinophil and GM colony production was found. The CFU-Eo stimulating effect of patient serum was in the range of the CFU-Eo stimulating effect of normal serum, after the addition of 5 u/ml of recombinant murine IL-5. The results suggest that eosinophilia was caused by IL-5 and GM-CSF production by rhIL-2 stimulated CD4 positive lymphocytes. The location on chromosomes 5 of the genes for IL-5, GM-CSF and IL-3 may be associated with regulation of expression, by a common mechanism, of all the factors known to be involved in eosinophil production. This mechanism may be activated by IL-2 stimulation. The separate location on chromosome 17 of the G-CSF gene may explain the ability of IL-2 to produce a distinct stimulus to eosinophil but not neutrophil production. PMID- 2094321 TI - Increased numbers of circulating haematopoietic progenitor cells after treatment with high-dose interleukin-2 in cancer patients. AB - Immunotherapy with recombinant interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been applied to patients with metastatic cancers for its antitumour activity. In the present study we investigated the effects of in vivo administration of IL-2 (3 x 10(6) U/m2/d, continuously i.v.) on haematopoiesis. Six patients with disseminated renal cell carcinoma, treated with IL-2 and LAK cells, were monitored for the numbers of white blood cells and circulating haematopoietic progenitor cells (HPC). During IL-2 treatment lymphopenia developed, followed by lymphocytosis after discontinuation of IL-2 infusions. IL 2 administration also resulted in neutrophilia and eosinophilia. Absolute numbers of circulating HPC declined markedly during IL-2 treatment. However, after completing IL-2 infusions, the numbers of circulating erythroid (BFU-E), myeloid (CFU-GM) and multipotential progenitor cells (CFU-GEMM) strongly increased, reaching a maximum after 5 d (day 10 from the start of IL-2 treatment). This increase did not result from repeated leucaphereses, since patients treated with IL-2 alone showed a similar response. In comparison with pretreatment levels the pool of circulating HPC expanded about 20-fold. This study illustrates that IL-2 treatment has a biphasic effect on the frequency of circulating BFU-E, CFU-GM and CFU-GEMM, causing a decrease during IL-2 infusion, followed by an increase after IL-2 administration. The total number of progenitor cells harvested by four consecutive leucaphereses is in the range that is commonly used for peripheral blood stem cell autografting. PMID- 2094322 TI - Clonal karyotype abnormalities and clinical progress in the myelodysplastic syndrome. AB - Clonal karyotype abnormalities in 124 patients with myelodysplastic syndrome are reviewed. 36% of patients had abnormalities at referral, the most common being 5q , +8 and lesions of chromosomes 7 and 20. Reduced survival was associated with the presence of either single or multiple clonal abnormalities at referral, abnormalities of chromosome 7 or 8 (either alone or with other lesions) and exclusively abnormal metaphases. The presence of 5q- alone did not appear to affect survival. Sequential studies were carried out in 77 patients of whom 12 showed karyotypic evolution. Reduced survival was observed in patients with an evolving karyotype but appeared to be due almost entirely to evolution in those patients whose initial karyotype was normal. Leukaemic transformation occurred more commonly in patients with an abnormal karyotype, particularly those with multiple abnormalities, and in patients with an evolving karyotype. Although the first appearance of an abnormal karyotype or an apparent evolution are important phenomena, it is probable that in some cases they merely represent expansion of a previously existing clone that has escaped detection. The distinction between true karyotypic evolution or clonal expansion and statistical variations due to small sample size and variability of samples may be difficult but needs to be taken into account in considering clinical significance. PMID- 2094323 TI - Clinicopathological features of acute undifferentiated leukaemia with a stem cell phenotype. AB - Over a 4 1/2-year period, 141 patients with acute leukaemia had morphologic, immunophenotypic and cytochemical studies performed at King's College Hospital. Seven cases were noted to have blast cells which did not express myeloid or lymphoid antigens or cytochemical staining indicative of differentiation but were HLA DR and CD 34 positive. Based on these criteria we have used the term stem cell acute leukaemia to denote these patients. There were five women and two men with a median age of 61 years (16-86). Presentation marrows were heavily infiltrated with blasts (greater than 95% in 6/7) which were usually pleomorphic. Type 2 blasts. Auer rods and dysplastic features were absent. Two of six cases studied showed clonal karyotypic abnormalities. Four patients were treated with high dose chemotherapy. Three of these achieved a complete remission but relapsed at 3, 6 and 7 months respectively. The median survival of the group was 7 months (2-12). We conclude that the stem cell acute leukaemias are a distinct clinicomorphological group which appear to have a poor prognosis with conventional chemotherapy. PMID- 2094324 TI - Philadelphia chromosome positive B-cell type malignant lymphoma expressing an aberrant 190 kDa bcr-abl protein. AB - The Philadelphia (Ph) chromosome translocation, t(9:22) (q34;q11) is found in some acute lymphoid leukaemias (ALL) and acute myeloid leukaemias (AML). Although cytogenetically all pH chromosomes appear similar, the 22q11 breakpoints found in acute leukaemias are of two kinds, those within the major breakpoint cluster region (Mbcr-1) of the BCR gene as found in chronic myelogenous leukaemia (CML), and those within the first intron of this gene. In the former group the molecular events are the same as those found in CML, p210 bcr-abl, encoded by 8.5 kb mRNA; however, a new aberrant protein, p190 bcr-abl, is found in the latter group. Ph translocation is also found in a few cases with malignant lymphoma, but it has not been characterized at the molecular level. We describe here a non-Hodgkin's lymphoma case with primary splenic presentation, which showed a complex Ph translocation. Neoplastic cells were of a B-cell origin (HLA-DR+, sIgM+, sIg lambda +, CALLA-). Molecular studies revealed the expression of p190 bcr-abl with no Mbcr-1 rearrangement. Our case indicates that the same Ph translocation as seen in acute leukaemias can be found in haematologic disorders other than leukaemias, suggesting that a c-abl gene activating mechanism may be involved in the pathogenesis of wide spectrum of haematologic malignancies. PMID- 2094325 TI - Cytogenetic analysis of 147 cases of non-Hodgkin's lymphoma: non-random chromosomal abnormalities and histological correlations. AB - A prospective cytogenetic study of patients with non-Hodgkin's lymphoma (NHL) presenting to one institution was commenced in 1983 as part of a larger study including histology, immunophenotyping, cytokinetics and survival. 175 patients were studied over 5 years and G-banded karyotypes were successfully obtained in 147. Chromosome abnormalities were detected in 135 cases (92%) with the commonest abnormality being t(14;18)(q32;q21) in 69 cases. Other non-random translocations were much less frequent, i.e. t(11;14) in seven cases and t(8;14) in four cases. Other specific structural changes included partial deletions of 6q (breakpoints ranging within q13-q23), 3q (breakpoints ranging within q21-q27), 1q and 10q22. Chromosome regions highlighted as being frequently involved in structural abnormalities were 11q13-q25, 1p22-p36, 3q21-q27 and 6q13-q23. Several specific recurring breakpoints were identified and these included 14q32, 18q21, 1p36 and 6q21. Frequently occurring numerical abnormalities were gains of chromosomes 3, 7, X and 12. Correlation with histological type showed, as expected, that t(14;18) was present in 89% of follicular lymphoma but also occurred in 30% of diffuse lymphoma. Abnormalities of 11q were correlated with the diffuse histologies as a group, whereas both numerical and structural abnormalities of chromosome 3 correlated with the diffuse large cell lymphoma (DLCL) subtype, and t(11;14) with diffuse small cleaved cell lymphoma (DSCCL). Although not statistically significant, abnormalities of 6q occurred twice as frequently in DLCL than in any other variety. However, several other commonly occurring abnormalities, such as extra copies of chromosomes 7, X, 12 and most of the structural abnormalities of 1p, did not correlate with any histological type. Therefore this large cytogenetic study has confirmed some previously reported correlations between specific chromosome abnormalities and histological subtypes of non-Hodgkin's lymphoma and has also identified some new correlations which may prove useful in the investigation of the biological basis of the disease. PMID- 2094326 TI - Lack of useful clinical predictors of response to splenectomy in patients with chronic idiopathic thrombocytopenic purpura. AB - We set out to identify clinical or analytical variables that might predict the response to splenectomy in patients with chronic idiopathic thrombocytopenic purpura (ITP). We retrospectively examined 138 mostly adult patients with chronic ITP, treated with splenectomy. Information was compiled from five Public Health Hospitals from a questionnaire and chart review. Sixty-one potentially prognostic variables were analysed by univariate and multivariate statistical methods. After multivariate analysis, age (relative risk = 1.02; CI 1-1.03) and a severity of the bleeding diathesis (relative risk = 1.6; CI 1.13-2.22) were independent prognostic factors for a sustained response to splenectomy. An independent analysis of the postsplenectomy counts showed that an early (days 1-3) thrombocyte count exceeding 156 x 10(9)/l cells increases the likelihood of a permanent unmaintained response. Our data indicate that the response to splenectomy in patients with chronic ITP cannot be adequately predicted on the basis of pre-splenectomy clinical or analytical variables. PMID- 2094327 TI - Basal and induced prothrombinase expression in platelets from patients with essential thrombocythaemia (ET). AB - Both the basal and the collagen plus thrombin-stimulated prothrombinase activities have been measured in platelets from eight patients with essential thrombocythaemia (ET). On a mean basis these activities were significantly lower than the values recorded for a group of age and sex matched control subjects. When the Ca2+ ionophore A23187 was substituted for the agonist mixture the induced expression of prothrombinase activity was essentially the same for the patient and control groups. It is suggested that the defect in prothrombinase expression seen with ET platelets may reside in either membrane signal transduction processes concerned with Ca2+ mobilization or in Ca2+ sensitive cytoskeletal control of membrane phospholipid topography. PMID- 2094328 TI - The effect of high doses of recombinant human erythropoietin on megakaryocytopoiesis and platelet production in splenectomized mice. AB - The effects of recombinant human erythropoietin (rHuEpo) on megakaryocytopoiesis and platelet production were investigated in splenectomized, sham-operated and intact mice. When splenectomized mice were injected with 50 U of rHuEpo daily for 4 d, peripheral platelet counts, megakaryocyte (MK) size and the percentage of mature MK (stage IV MK) increased from 1 to 4 d after the initial rHuEpo injection. The total number of marrow MK colony forming units (CFU-MK) increased from 2 to 4 d after the initial injection. Furthermore, from days 6 to 8, the total number of marrow MK also increased. In addition, when the dose of rHuEpo was increased to 20-200 U per mouse, clear dose responses were detected in platelet counts and MK numbers. When sham-operated and intact mice were injected with rHuEpo, no significant change in platelet numbers was detected. The number of MK, MK size and the number of CFU-MK increased only in spleen, not in bone marrow. Our data indicate that Epo has stimulatory effects on platelet production in vivo, if used in sufficient quantities. PMID- 2094329 TI - Denaturing gradient gel electrophoresis and direct sequencing of PCR amplified genomic DNA: a rapid and reliable diagnostic approach to beta thalassaemia. AB - The analysis of polymerase chain reaction (PCR)-amplified beta-globin DNA with allele-specific oligonucleotide (ASO) probes reveals a very heterogeneous spectrum of beta-thalassaemia in the Netherlands. However about 20% of the beta thalassemia mutations cannot be identified with this approach. The combination of specific amplification of certain regions of the beta-globin gene with denaturing gradient gel electrophoresis (DGGE) allowed us to rapidly localize several of these mutations to specific regions of the gene, which were again amplified and directly sequenced. We believe that the combination of DGGE and the direct sequence determination of PCR amplified genomic DNA represents a valid alternative to the 'ASO probes' approach, especially in countries where a very heterogeneous spectrum of beta-thalassaemia mutations occurs. PMID- 2094330 TI - Locus assignment of human alpha globin mutations by selective amplification and direct sequencing. AB - We describe a simple approach for molecular characterization and locus assignment of structural mutants by direct sequencing of enzymatically amplified DNA selective to alpha 1 and alpha 2 globin gene regions. Nucleotide substitution of two structural variants (Stanleyville II alpha 2(78Lys) and J Mexico alpha 2(54Glu) were determined and their encoding loci were specified. The amplified segment encompasses sequences upstream of the CAAT box to downstream of the Poly(A) addition signal. Hence all of the alpha globin structural variants and most of the nondeletion alpha thalassaemic mutants should be characterizable by this approach. PMID- 2094331 TI - Effects of deficiencies of glycophorins C and D on the physical properties of the red cell. AB - Red cells of the rare Leach phenotype lack the membrane glycophorins C and D, and a proportion of the red cells are elliptocytes. Judging from tests on suspensions of red cell ghosts sheared rotationally in an ektacytometer, it has previously been suggested that these membranes are relatively fragile and poorly deformable. We have carried out analyses of individual red cells to investigate possible factors which underlie the physical changes in these glycophorin-deficient cells. Micropipette analysis of the red cell membrane showed that the rigidity and viscosity were normal, both for elliptocytes and discocytes, for three donors deficient in glycophorins C and D. Red cell transit times through 5 microns pores, measured electronically for 2000 individual cells, showed no differences from controls. It was confirmed that the index of deformation obtained using an ektacytometer was reduced, but our results suggest that this arises from shape rather than membrane changes. The elliptocytes were found to have a lower volume and surface area than discocytes from the same donor (measured by micropipette aspiration of single red cells), and were rarely found in less dense red cell fractions. No reticulocytes were found to be elliptical. These data suggest that the elliptocytes are older red cells, and are formed from red cells which are initially released into the circulation with normal shape. Their elongated shape might arise from permanent distortion of the unstable membrane by shear forces in the circulation. PMID- 2094332 TI - Total circulating red cells versus haematocrit as the primary descriptor of oxygen transport by the blood. AB - Peripheral haematocrit (PCV) is the traditional target and monitor in many transfusion regimens. Without negating the importance of PCV as a determinant of whole blood viscosity, the present article outlines two important reasons why the red cell volume (RCV) should replace PCV in the central target role during blood transfusion in intensive care and other emergency situations: 1. PCV reflects both RCV and plasma volume (PV) and is therefore not directly proportional to the total blood oxygen carrying capacity. At best, the relationship between PCV and RCV is hyperbolic and this is often overlooked when relating the two parameters in practice. At worst, the hyperbolic relationship is unreliable because PV and RCV can vary independently and the PCV is a fluctuating ratio of variable numbers. 2. PCV is not a good indicator of blood volume (BV), which is another important determinant of oxygen delivery to tissues and a crucial parameter in intensively managed patients. BV is directly proportional to RCV and this relationship also is often overlooked in clinical practice. The recommended values for RCV are 30 ml/kg in men. 25 ml/kg in women and between 30 ml/kg and 45 ml/kg in neonates within the first week of life. PMID- 2094333 TI - Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). I. Iron chelation and metabolic studies. AB - A long-term clinical trial of 1-15 months has been carried out with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in 13 transfusion-dependent iron loaded patients. Urinary iron excretion was greatest in patients with thalassaemia major and was related to the number of previous transfusions but not to the serum ferritin level. Substantial increases of urinary iron were observed in all the patients when the frequency of the daily dose was doubled and in response to 2 x 3 g L1 daily 11 of 12 patients tested excreted greater than 25 mg iron daily, the mean daily intake of iron from transfusion. Serum ferritin levels have fluctuated but overall have remained unchanged. Pharmacological studies in five patients have indicated rapid absorption probably from the stomach and variable plasma half life of 77 +/- 35 min (X +/- SD). Glucuronation was identified as a major route of L1 metabolism. Short-term intensive chelation studies using repeated administration of L1 resulted in further increases of urinary iron excretion by comparison to a single dose. In one case 325 mg of iron were excreted in the urine following the administration of 16 g (5 x 2 g + 2 x 3 g) within 24 h. Iron excretion studies were carried out in six transfusional iron loaded patients who were maintained on a low iron diet before and during chelation. No significant increases of faecal iron excretion were observed with L1 using daily doses of up to 3 x 3 g and 4 x 2 g. The high level of compliance during treatment with L1 and the levels of urine iron excretion that can be achieved increase the prospects for oral chelation in transfusional iron-loaded patients. PMID- 2094334 TI - Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). II. Clinical observations. AB - 1,2-Dimethyl-3-hydroxypyrid-4-one (L1) has been given daily for 1-15 months to 13 transfusion dependent iron loaded patients. No significant change occurred in liver, renal or cardiac function, ECG and radionucleotide angiocardiogram, in audiometry tests and in visual function and electrical retinography. No skin rashes, gastrointestinal symptoms and no neurological changes that could be detected clinically were observed. Two of the patients died of their underlying diseases. One patient had severe cardiac abnormalities before receiving L1 and died of congestive heart failure with infections 5 weeks after stopping a 2-month course of L1. The other, a patient with myelodysplasia suffered recurring infections due to progression of the disease. Joint and muscle pains occurred in five patients. In two these disappeared despite continuing the drug; another patient developed swollen ankle joints which gradually resolved on stopping L1 therapy; a patient with underlying osteoarthritis complained of mild pain and stiffness in her knees which remained intermittent both on and off the drug while in the fifth patient peripheral small joint swelling and pain present before starting L1 improved with L1 therapy. One patient, with Blackfan Diamond anaemia, developed a Lw red cell antibody 6 months after commencing L1. This disappeared on stopping the drug and did not reappear. She then developed severe agranulocytosis and thrombocytopenia 6 weeks after recommencing L1 after 3 months discontinuation of the drug. No other patient showed a change in granulocyte or platelet count. PMID- 2094335 TI - Splenic irradiation as primary therapy for prolymphocytic leukaemia. PMID- 2094336 TI - Homozygous deletion of FMS in a patient with the 5q- syndrome. PMID- 2094337 TI - Leukaemia following exposure to microwaves: analysis of a case report. PMID- 2094338 TI - Expression of the p75 interleukin-2 receptor (beta subunit) in acute and chronic leukaemia. PMID- 2094339 TI - High and low affinity IL-2 receptors on human leukaemic blast cells. PMID- 2094340 TI - Factor XIII subunit B deficiency. PMID- 2094341 TI - Studies regarding the antioxidant effects of selenium on top swimmers. AB - The authors performed another controlled trial in 33 top swimmers (16 girls and 17 boys) in order to make evident some acute and chronic effects (antioxidant) of selenium. Lipid peroxides (MDA-malondialdehyde), nonproteic--SH (essential glutathione) in the serum and blood lactate had been recorded initially on basal conditions and after 2 h endurance training (swimming) accompanied by a per oral administration of 150 micrograms selenium (respectively placebo); one week later we applied the cross-over method. In another trial we continued the treatment with 100 micrograms selenium daily for 14 days (n = 9), respectively placebo (n = 7) and then we applied the crossover method for another 14 days. The above biochemical parameters were recorded initially at rest, under basal conditions, after 14 days of treatment and again after 14 days of treatment, when crossing over. No significant changes were noticed after a single dose + 2 h hard training, both under selenium and placebo treatment and also when the cross-over method was applied. Fourteen days of selenium treatment induced significant changes of lipid peroxides (especially when the subjects came after placebo) and nonproteic--SH, compared to placebo, changes which support the idea of some antioxidant effects of selenium which might be useful in endurance athletes. PMID- 2094342 TI - Intracardiac electrical discharge in terminating atrial fibrillation. AB - A new intracavitary technique for internal defibrillation in atrial fibrillation is presented. The discharge takes place between the distal electrodes of the catheter placed in the right atrium and a thoracic paddle. Four cases are discussed, and the indications for this type of defibrillation are considered. Internal defibrillation can be done when, for other purposes, an electrode catheter is already placed in the right atrium. PMID- 2094343 TI - Preatrial activity recorded by intracavitary and transthoracic techniques. AB - Two methods to record preatrial activity, that is, sinus node potential are presented. One, during right atrial catheterization through an electrode catheter, and the other, using transthoracic recordings with a high amplification and derivation of the electric signals. The sinus node potential duration represents the sino-atrial conduction time (SACT), a useful parameter for the sinus node function evaluation. PMID- 2094344 TI - Effects of ingestion of radioactive cesium on behavioral indices in rats. AB - The experiments were carried out on 35 male (M) and female (F) rats contaminated by ingestion of Cesium--137(Cs) for 38 or 84 days; the total Cs activity was 288 Bq 460 Bq, and respectively. The duration of forced swimming decreased significantly in the contaminated groups as compared with controls (n = 16). The active avoidance reaction in the shuttle-box shows an increase in F groups and a decrease in M groups. The total latency time of the same reaction was lower in F and M treated rats on the first day of learning. The score of aggressive behavior rose significantly, especially in group F. These results can be explained by the sex dependence of Cs accumulation and by the neurotoxic action of the radionuclide on several central neural areas including monoaminergic and endocrine mechanisms. PMID- 2094345 TI - Coagulation and fibrinolysis in rats after confinement hypokinesia. AB - Our previous experiments (14) (15) dealt with the dynamic of the fluid-coagulant equilibrium in rats after exposure to confinement hypokinesia (CHK) at different time intervals, 1, 3, 7, 21, 28 and 35 days. We found a decreased Quiq and Howell time (QT and HT) in some relation with the time of exposure, with a tendency to normalization after 21 days. The same evolution was shown by the number of thrombocytes and of the euglobulin lysis time (ELT). In this work we prolonged the exposure to CHK for 60 days, an interval after which a series of other functional parameters significantly approached initial control values (16). We found an important approach to normal values also with the QT, HT, Elt and with the number of thrombocytes. Concomitantly, the plasma concentration of corticosterone (the principal glucocorticoid of rats), that increased over shorter intervals, approached also control values after 60 days of exposure to CHK. Nevertheless, it can not explain the changes of coagulability, because it decreases after adrenalectomy but the QT, HT and thrombocytes are already decreased. For these and other reasons it results that the relation of adrenal hormones to coagulation needs be further clarified. PMID- 2094346 TI - The clearance of colloidal particles by Kupffer cells in collagen disease. AB - The Kupffer cells clearance of colloidal 198Au particles with a diameter of 200 300 A was estimated in 14 subjects with different collagen diseases: 7 without previous treatment and 7 under immunodepressive treatment compared to 10 controls. No difference between the subjects with collagen disease and controls was observed. The group with collagen disease under immunodepressive treatment has lower Kupffer cells clearance for colloidal gold particles than non-treated patients, without statistical significance. PMID- 2094347 TI - [The action of prednisone on the modulation of the immune system in chronic hepatitis]. PMID- 2094348 TI - Fibronectin and lymphocyte blast transformation. AB - Purified human plasma fibronectin (Fn) added to human peripheral blood leukocytes culture, from 22 healthy blood donors, phytohemagglutinin (PHA) stimulated, enhanced mitogen action in blast transformation. Daily measurement (between 1-6 days) of Fn concentration in culture supernatants incubated with PHA, Fn and associated doses of Fn and PHA, pointed out a significantly increased Fn concentration, on the fourth day, in the cultures incubated with Fn and PHA. On the fourth day of PHA stimulated cultures were found, the increased Fn concentration, as well as the maximum blast transformation. Our data suggest that Fn, synthetized by activated macrophage in intercellular cooperation processes is released in culture supernatants with a maximum on the fourth day. These results show the possible role of Fn to influence blast transformation enhancement of mitogen action. PMID- 2094349 TI - The clinical forms of systemic neuroendocrine pathology (neuroendocrine cybernosis). AB - Six forms of regulation of neuroendocrine system pathology are here presented. For this pathogenic category it was proposed the term of "systemic neuroendocrine pathology" (1979) and that of "endocrine cybernosis (1971) for its clinical forms. Clinical and pathogenic peculiarities of endocrine blocking cybernoses with negative feed-back disappearance, substitution cybernose as in Graves Basedow's syndrome and hormonal circadian rhythm troubles are described. The semiology of the clinical forms is partly known, but their pathogeny is still locally and regionally interpreted. There are primary and secondary lesions, characteristic of each clinical category of the systemic pathology, but the prevailing expression is the systemic one. The treatment of neuroendocrine cybernoses must be dominated by regulatory medication. PMID- 2094350 TI - Intracellular pH: functions and regulatory mechanism. PMID- 2094352 TI - Rays of light into the "black boxes" regulating biological ageing? PMID- 2094351 TI - Effects of the perfusion of amrinone and milrinone on the ventricular fibrillation thresholds in isolated Langendorff perfused guinea-pig hearts. PMID- 2094353 TI - Age-related changes in skeletal muscle function. AB - This review examines current evidence for the existence of aging processes in skeletal muscle fibers. Experimental data demonstrating changes with age in nerve muscle interaction, excitation-contraction coupling, mechanical properties and muscle energetics are discussed, with emphasis on factors in addition to aging which might account for the observed results. The effects of dietary restriction, exercise and disease on age-related changes in muscle function are also discussed. Results of recent studies highlight the need to establish the health status of subjects and animals used for aging research as well as the need to obtain data from a wide variety of muscles. Although marked decline of muscle performance with age is documented by early studies, recent work indicates that at least some muscles of healthy individuals and animals do not show an age related decline in function or an impaired ability to respond to exercise. Decreased physical performance in the elderly may be due to factors extrinsic to aged skeletal muscle fibers. PMID- 2094354 TI - Self-rating and objective memory testing of normal and depressed elderly. AB - This study aimed to assess the relationships between the scores of subjective assessment (metamemory) and those of performance testing for memory, on the one hand, and the level of depression, on the other. A hundred and eighty elderly subjects (102 women and 78 men; mean age 65.7 years) were selected for the study. They showed neither intellectual impairment (as assessed through Mini Mental State test: MMS) nor neuropsychiatric symptoms. Each subject was administered the Randt Memory Test (RMT) for performance testing, the Sehulster Memory Scale (SMS) for the subjective assessment, and the Geriatric Depression Scale (GDS). A MULTCOVA analysis showed that both age and the depression level are negatively correlated with both the measures (Acquisition-Recall: AR; Delayed Memory: DM) of the RMT. The scores of the second (memory complaints) of the three sets of SMS were positively correlated with those of AR and DM indices. A Multivariate Regression Analysis showed that in males age and the depression level were significant regressors for both AR and MD scores while in females only the depression level was a significant regressor for AR and only age was a significant regressor for DM. Our results suggest that a) the relationships between the depression level and memory functioning are close, although not fully homogeneous in men and women; and b) that the scores in some areas of metamemory parallel, independently of the level of depression, the performance outcomes of memory functioning. PMID- 2094355 TI - Identification of the needs of elderly people in Northern Ireland. AB - This paper presents the results of a survey on persons over the age of 65 in Northern Ireland. One of the aims of this research was to identify and measure the needs of the elderly population in order to develop a Programme of Care. It would seem logical that the problems of the elderly tend to increase with age. Since the population is becoming older and given the commitment to community care, this will have serious implications for the National Health and Social Services. The present survey was carried out using a questionnaire to extract details concerning the individuals' mental state, ability for self-care and household duties, mobility, accommodation, social activities, general health, strain imposed on others and current support from the statutory services. The results for each category were then presented for 5 age-groups: 65-69, 70-74, 75 79, 80-84 and 85+. Specific problems in relation to home help provision and social facilities such as day care are also discussed. PMID- 2094356 TI - Cellular and synaptic alterations in the aging brain. AB - The morphological and functional impairments observed in the aging brain are discussed in the framework of theoretical concepts, such as the existence of different modalities of intercellular communication and of specific trophic features in the central nervous system. The relevance of changes at the cellular level (disappearance of neuronal cell bodies and proliferation of astroglial cells) and at the synaptic level (alterations in neurotransmitter and receptor levels) is discussed. Two, non-mutually exclusive hypotheses are advanced to explain the frequent absence of correlation between neuropathological findings and functional deficits in aged patients. According to the first, the physiological reshaping of brain circuits during aging may lead to "wrong" readjustments of neural networks (e.g. due to less effective endogenous and exogenous orienting signals) causing minor morphological alterations but marked functional deficits. The second hypothesis maintains that the absence of correlation between neuropathological and functional deficits is due to the impairment of restricted neuronal populations ("pacemaker and command neurons") which play a special role in the hierarchical organization of neuronal networks. These neurons (inter alia, peptidergic neurons) may also be involved in volume transmission (diffusion of electrical and chemical signals in the extracellular fluid to reach distant targets). Moreover, the relevance of glial cells, not only as regulators of the extracellular medium but also on the basis of their trophic links with neurons, is considered. Finally, the interplay between trophic factors and therapeutical experience for the maintenance and/or recovery of an impaired function in elderly patients is discussed. PMID- 2094358 TI - Cancer registry types: goals and operations. PMID- 2094359 TI - Cancer registries: methods and procedures. PMID- 2094357 TI - Predictors of high functional capacity and mortality in elderly Finnish men. AB - Factors predicting high functional capacity in old age and 25-year mortality were studied in 1711 men aged 40 to 59 years. The study population was that of the East-West Study, i.e. the Finnish part of the Seven Countries Study. After the 25 year follow-up (in 1984) 766 men were still alive. Nonsmoking and good pulmonary function in earlier middle-age and the absence of coronary heart disease, cerebrovascular disease or emphysema in later middle-age predicted high functional capacity in old age. High systolic blood pressure, low forced vital capacity, smoking, and the presence of coronary heart disease predicted mortality in the next 10 to 25 years. Although mortality rates were higher in eastern Finland, the predictors were similar in both the eastern and the southwestern parts of the country. PMID- 2094360 TI - The importance of registries in studying the etiology of insulin-dependent diabetes mellitus. PMID- 2094361 TI - A neurologist's view of a registry for Alzheimer's disease. PMID- 2094362 TI - Searching for the molecular basis of aging: the need for life extension models. PMID- 2094363 TI - Degenerative, non-atherosclerotic cardiovascular disease in the elderly: a clinico-pathological survey. AB - Cardiovascular disease, the major cause of death in the elderly, is mostly ascribable to complications of coronary atherosclerosis: angina pectoris, myocardial infarction, and sudden death. However, other degenerative diseases involving several cardiac structures exist, and should be distinguished from age related cardiac changes. Extensive dystrophic calcification determines aortic stenosis, and may affect either a normally tricuspid or a congenitally bicuspid valve. Surgical valve replacement is now a low risk option, even in elderly persons, whereas the efficacy of balloon valvuloplasty is questionable. Aortic incompetence in adults and aged persons is mostly the consequence of aortic tunica media atrophy with anular ectasia, in the setting of nearly normal aortic leaflets. Mitral valve prolapse is the main cause of mitral incompetence; spontaneous cordal rupture is a late complication in the natural history of this disease, thus warranting prompt surgical valve repair or replacement. The entire spectrum of cardiomyopathies is observed in the elderly: dilated, hypertrophic, restrictive, arrhythmogenic. Cardiac amyloidosis is by far the most frequent secondary form and leads to congestive heart failure by impairing ventricular compliance. Idiopathic fibrosis of the specialized AV junction or dystrophic calcification of central fibrous body are the usual substrates of AV block, which requires pace-maker implantation. Nonrheumatic atrial fibrillation, due to fibro fatty degeneration of the atrial musculature or dilated left atrium, carries a high risk of thromboembolic complications and cerebral accidents; oral anticoagulants have proven to be effective in preventing stroke. Aortic dissecting aneurysm is a spontaneous laceration, and usually a complication of longstanding systemic hypertension; exceptionally, spontaneous dissection may primarily occur in the coronary arteries. In conclusion, longevity at present is mostly threatened by cardiovascular disease, among which the role of degenerative, non-atherosclerotic disorders may be greater than thought. PMID- 2094364 TI - Dimensions of loneliness. AB - Experiences of loneliness have been studied in 2795 Swedish inhabitants aged 15 80. Three different kinds of feelings of loneliness have been identified: intensity/quantity of loneliness, inner loneliness and positive loneliness. Contrary to common belief, the analysis shows that the intensity/quantity of loneliness is higher among young subjects whereas the degree of inner loneliness is slightly higher among older subjects. Both developmental experiences during childhood/adolescence and social conditions at present are correlated with the experience of loneliness in old people. PMID- 2094365 TI - Pressure sores in nursing home patients. AB - One hundred and sixty-seven patients were part of a cross-sectional study examining pressure sores in patients in skilled nursing facilities. Every patient admitted to this study was physically examined for the presence or absence of pressure sores and evaluated according to a standardized procedure. Using logistic regression analysis, the variables most significantly associated with pressure sores included a history of hypertension, infection, unwelcome response to visitors, history of poor dietary intake and a pattern of slow or poor response to commands. Knowledge of these factors may lead to more intensive efforts to develop better methods of prevention and treatment of pressure sores. PMID- 2094366 TI - Age and glucose tolerance in healthy subjects. AB - An important and still controversial issue is the role played by the aging process itself in the metabolic alterations observed in aged people. We previously reported that a group of normal elderly people exhibited glucose disposal comparable to that of young controls. In the present study we investigated the effect of age on beta-cell secretion, by analyzing C-peptide measurements. Ten elderly men (E, 70 +/- 2 years) with normal oral glucose test and ten young subjects (Y, 27 +/- 1 years) with matching ideal body weight formed the study group. They were studied under highly dynamic conditions by means of a 0.3 g/kg i.v. glucose tolerance test. Fasting glucose and insulin were not different in the two groups (Y: 87 +/- 2 mg/di, E: 88 +/- 3, p greater than 0.1; Y: 50 +/- 7 pM, E: 36 +/- 7, p greater than 0.05). Glucose-insulin data set was analyzed by means of the minimal model of glucose disappearance which provided two parameters for every individual, yielding a quantitative description of glucose utilization: i.e., SI, the index of insulin sensitivity, and SG, the fractional glucose disappearance at basal insulin (glucose effectiveness). Both parameters were unaltered by age (SI = Y: 6.30 +/- 0.41 10(-4)min-1/(microU/ml), E: 7.11 +/- 0.72, p greater than 0.1; SG = Y: 0.020 +/- 0.003 min-1, E: 0.019 +/- 0.002, p greater than 0.1). C-peptide time course in elderly people was systematically lower than in the control group (basal levels: Y: 252 +/- 36 pM, E: 129 +/- 17, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094367 TI - Mortality postponed and the unmasking of age-dependent non-fatal conditions. AB - Mortality occurs at older ages in our growing and salubrious population. At present, fewer than 20% of all deaths, in Sweden, occur before age 65 with 18% of the Swedish population 65 and over. In the United States, 24% of deaths occur before age 65 with only 12% of the population age 65 and over. All countries in the developed world will have approximately 20% of their populations age 65 and over by about 2020. At that time, the percentage of deaths occurring prior to age 65 should range from 14%-16%. Thus future gains in morbidity and mortality will be influenced, to a lesser extent, by events prior to age 65 and prevention and health promotion strategies post age 65 become increasingly important. Active life expectancy, a developing concept, refers to the years lived in good health with no functional limitations. The period after active life expectancy consists of years of compromised health and well being. At present, each year gained of active life expectancy incurs almost four years of compromised health. A group of age-dependent nonfatal conditions are largely responsible for increased prevalence of social and physical deficits with age. These include dementia, osteoarthritis, diminished hearing and visual acuity, incontinence, depression, widowhood, isolation and institutionalization. Age-specific incidence of most of these conditions is unknown. There is little evidence, however, that adding years to life has postponed their age at onset. For these conditions, postponement is the major mechanism of prevention. We are attempting to construct time trends concerning the age-specific incidence and the ability to postpone age-dependent conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094368 TI - The magnesium load test: experience in elderly subjects. AB - While serum magnesium is the simplest and most widely used approach to the evaluation of magnesium status, it is recognized that a normal serum level can occur in the presence of tissue depletion. The magnesium load test is a reliable indirect method of assessing whole body magnesium status, but experience with its use in older subjects is limited. The initial aim was to establish a range of results for the magnesium load test in older subjects who were likely to be tissue depleted. Such data would enable more accurate interpretation of the test in older subjects with normal serum levels who might be tissue-magnesium depleted. Magnesium loading was performed in 43 female subjects, average age 83 years, with serum magnesium levels not exceeding 0.75 mmol/l (mean 0.63 +/- 0.09 mmol/l) and lower than recommended dietary magnesium intakes. Magnesium sulphate was given intravenously, 0.25 mmol magnesium/kg body weight at a rate of 2.5 mmol/hour. Twenty-four-hour urine magnesium was determined for two days before the test and on the day of test from the start of the infusion. The test was abandoned in 13 other subjects because it was not possible to obtain three consecutive accurate urine collections despite careful selection. In the remaining 30 subjects, average magnesium retention was 62% (range 15-98%). Serum magnesium appeared a better guide to tissue status than urine magnesium, but creatinine clearance correlated better with the degree of magnesium retention than either serum or urine magnesium levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094369 TI - The east Boston Alzheimer's Disease Registry. PMID- 2094370 TI - The University of Pittsburgh Alzheimer's Disease Patient Registry: the Monongahela Valley Independent Elders Survey (MoVIES). PMID- 2094371 TI - A report on two projects prior to the creation of the Iowa Registry. PMID- 2094372 TI - The University of Iowa Prototype Alzheimer's Disease Registry: plans and progress. PMID- 2094373 TI - An Alzheimer's disease patient registry: the Prototype Alzheimer Collaborative Team (PACT). PMID- 2094374 TI - Aging of the population: demographic and social changes. PMID- 2094375 TI - Immune dysfunction in the elderly: effect of thymic hormone administration on several in vivo and in vitro immune function parameters. AB - The effects of short-term thymic hormone administration on age-associated immune function were evaluated. Two groups of individuals greater than 65 years of age were treated for 30 days with thymic extracts (TP1) or placebo; before and after this treatment a panel of in vitro and in vivo parameters was determined according to a very rigorous experimental protocol. In most individuals, TP1 treatment was associated with an improvement in cutaneous delayed-type response to PPD. Moreover, an increase in a circulating T cell subpopulation bearing the CD45R surface antigen ("virgin" T cells), and in NK cell cytotoxic activity was also observed in some subjects. Finally, lymphocyte responsiveness to PHA tended to increase, while no effect on lymphocyte ability to produce IL-2 following mitogen stimulation was observed. These findings suggest that TP1 treatment may influence age-related alterations in immune function parameters in some subjects. PMID- 2094376 TI - Cellular enzymatic activities in the articular cartilage of osteoarthritic and osteoporotic hip joints of humans: a quantitative cytochemical study. AB - Quantitative cytochemical methods were applied to measure the activity of several oxidative enzymes in human articular cartilage of the femoral head obtained from osteoarthritic patients (OA) and from patients with fractured femoral neck (OP) due to primary osteoporosis. In both conditions, lactate dehydrogenase (LDH) was found to be the most active one followed by two additional cytosolic enzymes: glyceraldehyde 3-phosphate dehydrogenase (GAPD) and glucose 6-phosphate dehydrogenase (G6PD). On the other hand, the activity of mitochondrial enzymes such as succinate dehydrogenase (SDH) and beta-hydroxyacyl dehydrogenase (HOAD), appeared much lower in degree. Except for HOAD, all the other enzymes exhibited a high degree of activity along the inner zone in the cartilage, i.e., zone 3b, indicative of an apparently more active metabolism in the osteochondral junction. G6PD activity was significantly higher (p less than 0.01) in OP than in OA patients. By contrast, SDH appeared more active in specimens obtained from OA patients. The remaining enzymes showed no appreciable activity differences between cartilages of OP and OA patients. These findings suggest that oxidative enzyme activity in chondrocytes involved in osteoarthritis does not differ substantially from that in cartilage of OP patients. PMID- 2094377 TI - The impact of socio-medical factors and oral status on dietary intake in the eighth decade of life. AB - The impact of different background factors on dietary intake was studied in a representative sample of 94 men and 89 women (mean age 74.6 years). More women than men in the sample felt lonely, lived alone and felt ill. The women also had more frequent and more severe mandibular dysfunction problems. Many individuals showed an unsatisfactory dietary intake according to the Recommended Dietary Allowance in Sweden (RDA-S). A multivariate analysis showed that sex, age, education, general living conditions, anamnestical and clinical dysfunction indices and dental status influenced dietary intake. Subjective chewing problems were strongly connected with dental status and constituted one of the most important single variables explaining the differences in dietary intake. This study shows the importance of asking elderly patients about their living conditions and chewing problems, as well as evaluating dental status and function from a "masticatory performance perspective" and offering adequate dietary advice. PMID- 2094378 TI - Emergency department utilization: a comparative analysis of older-adults, old and old-old patients. AB - A comparative analysis of Emergency Department (ED) utilization by 2936 older adults, old, and old-old patients was conducted in the only hospital available for residents of a vast geographical region. All patients (45+) who arrived at the ED during the first week of every even month from September 1986 to August 1987 were selected for the study. No significant differences were found among the three groups with regard to sociodemographic characteristics other than age. Data showed that the old-old use the ED approximately twice as much as the old and the older-adults; they also use the ED more often than the two other groups during the winter season. These two findings indicate the utility of viewing the old-old not only as a part of the elderly population, but also as a unique risk group. Hospitalization rates present a different pattern: they double in each age group moving from the youngest to the oldest. Complaints of an internal medicine nature are more often presented by the two groups of the elderly in comparison to the older-adults, and are followed by more frequent hospitalizations in internal medicine wards. Such findings have practical implications, and should be taken into consideration by policymakers. PMID- 2094379 TI - Confusional symptomatology distinguishes early- and late-onset Alzheimer's disease. AB - Symptoms of confusion were examined in 75 patients with Alzheimer's disease (AD). Mild confusion was found in 20, and mode-rate/severe confusion in 8 patients. Confusion was more frequent in the late-onset (26/44-59%) than in the early-onset AD group (2/31-6%) (p less than 0.0001), and patients with confusion were older (p less than 0.0001) than those without confusion. The frequency of confusion was higher in patients with ischemic heart disease (13/28-46%) than in patients without this vascular factor (10/47-21%) (p less than 0.05). An inverse relation was found between confusional symptomatology and parietal-lobe symptoms. The findings in this study suggest that a subgroup of AD patients, fulfilling the NINCDS-ADRDA criteria for probable AD, is characterized by a clinical picture of mild confusional symptomatology together with no or mild parietal-lobe symptomatology, higher age and higher frequency of ischemic heart disease. This group contrasts with the other subgroup of pure AD, which is characterized by a clinical picture of marked parietal-lobe symptomatology, almost no confusional symptomatology, lower age and lower frequency of ischemic heart disease. PMID- 2094380 TI - University of Washington Alzheimer's Disease Patient Registry (ADPR): 1987-1988. PMID- 2094381 TI - Mayo Clinic Alzheimer's Disease Patient Registry. PMID- 2094382 TI - Consortium to Establish a Registry for Alzheimer's Disease (CERAD): clinical, neuropsychological, and neuropathological components. PMID- 2094383 TI - Implications for planning registries for dementing diseases. PMID- 2094384 TI - [New aspects of salmonellosis]. PMID- 2094385 TI - [Focal hepatosplenic candidiasis in patients with cancer]. PMID- 2094386 TI - [Focal salmonellosis in Spain. Presentation of 14 cases and review of the literature]. AB - A study of the 14 focal salmonelloses diagnosed in the Hospital Clinico Universitario from Salamanca during the last years is presented, along with a review of the major series reported in Spain. The most common focal salmonelloses were osteoarticular, representing one third of cases. The most common underlying condition was diabetes mellitus, which involved more than 40% of patients. The pathogenetical peculiarities of salmonellosis in these patients and their relation with the higher prevalence of focal salmonellosis in particular diseases are discussed. PMID- 2094387 TI - [Salmonella enterica in the Aviles health district (Asturias). Microbiological, clinical, and epidemiological aspects]. AB - The results of the follow up of the Salmonella enterica infections seen in the Hospital San Agustin in Aviles (Asturias) from 1984 through 1987 are reported. The incidence was 19.49% of the overall number of fecal cultures and 0.47% of the overall number of blood cultures. 326 patients were involved: acute gastroenteritis (314 cases, with bacteremia in 10), typhoid fever (7 cases) and other infections (5 cases); 172 patients required hospital attention and 115 antimicrobial therapy. The morbidity rate was 47.94 per 10(5) and 44 outbreaks were recorded. 19% of strains were resistant to antibiotics, particularly Typhimurium and Virchow serotypes. PMID- 2094388 TI - [Biochemical, physiological, and enzymatic study of 78 strains of Helicobacter (Campylobacter) pylori isolated from gastroduodenal biopsies]. AB - A biochemical, physiological and enzymatic study of 78 C. pylori strains isolated from gastroduodenal biopsies is reported. All strains were positive in the oxidase, catalase and urease tests. 97.4% produced SH2 in the lead acetate band and 79.4% showed beta-hemolytic activity in sheep blood agar. In the antibiotic selection tests, C. pylori was characterized to be resistant to nalidixic acid and sensitive to cefalotin . The enzymatic study demonstrated the presence of acid and alkaline phosphatases. This finding and the urease test give C. pylori a define bacteriological character which differentiate it from the remaining campylobacteria. PMID- 2094389 TI - [Analysis of the sensitivity of mesophilic Aeromonas isolated from feces to antibiotics of everyday use]. AB - The sensitivity to antibiotics of 56 mesophilic strains of Aeromonas (20 A. caviae, 18 A. sobria and 18 A. hydrophila) isolated from the feces of patients with enteritis, 89.2% of strains had some type of resistance, such as 83.9% to ampicillin, 32.1% to carbenicillin, 28.8% to cefalotin, 5.3% to co-trimoxazole and 1.7% to chloramphenicol. 48.2% of strains were simultaneously resistant to two of the tested antibiotics, 3.5% to three and 5.3% to four. 95.7% of ampicillin resistant strains were beta-lactamase producing. A. sobria was more sensitive to cefalotin (MIC less than 8 micrograms/ml) than the remaining species. This finding supports the use of that marker for identification. PMID- 2094390 TI - [Treatment of the most common infections in patients with human immunodeficiency virus infection. Task-force on AIDS of the Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica]. PMID- 2094391 TI - [Selection bias]. PMID- 2094392 TI - [Diarrhea and dilatation of the colon]. PMID- 2094393 TI - [Pulmonary mass]. PMID- 2094394 TI - [Subacute bacterial endocarditis caused by Cardiobacterium hominis]. PMID- 2094395 TI - [A new case of endocarditis caused by Actinobacillus actinomycetemcomitans]. PMID- 2094396 TI - [Infectious aortic endocarditis caused by Streptococcus viridans mitis and acidominimus in a parenteral drug addict]. PMID- 2094397 TI - [Ciprofloxacin in the treatment of a case of endocarditis caused by Eikenella corrodens]. PMID- 2094398 TI - [Bacteremia caused by Actinobacillus actinomycetemcomitans and fever of unknown origin]. PMID- 2094399 TI - [Endocarditis caused by Actinobacillus actinomycetemcomitans on a prosthetic valve]. PMID- 2094400 TI - Pelvic inflammatory disease: current approaches and ideas. PMID- 2094401 TI - Management of pelvic inflammatory disease. PMID- 2094402 TI - Sexually transmitted diseases and rape: the experience of a sexual assault centre. AB - Epidemiological data and rates of sexually transmitted diseases (STDs) are presented from a group of 90 women screened following rape. Forty-eight (53%) women knew their assailant. In 6 cases multiple assailants were involved. In 21 (23%) rapes weapons were used. Of 47 women examined within 48 hours of rape, 17 (36%) had evidence of genital trauma. Anal injury was common (8 of 11, 73%) in those reporting anal intercourse. Anal assault (17 of 90, 19%) and oral assault (16 of 90, 18%) commonly accompanied rape. STDs were diagnosed in 13 (14.4%) women, 3 having mixed infections. Neisseria gonorrhoeae was isolated in 2 women, Chlamydia trachomatis in 7, Trichomonas vaginalis in 6, genital warts in 2 and Pediculosis pubis in 2 women. Five of 16 cervical cytology results showed abnormalities, 2 were suggestive of CIN. Eleven of 13 women with an STD (84.6%) had been sexually active within the 3 months prior to the rape. Previous sexual activity may be the most relevant factor determining those most at risk of harbouring an STD. PMID- 2094403 TI - Heterosexually acquired human immunodeficiency virus infection in women in Copenhagen: sexual behavior and other risk factors. AB - In order to describe the risk pattern including sexual behaviour among HIV infected women in Copenhagen we studied the charts of all women tested seropositive between January 1985 and August 1988 in the three main hospitals handling HIV/AIDS. One hundred and fifteen women were positive for HIV antibodies: 35 (31%) were infected by heterosexual contact and 63 (55%) were intravenous drug users. Among the heterosexually transmitted cases 25 (71%) had intercourse with a man from a high risk group and nine women had intercourse with a known HIV antibody positive man without known risk factors. Use of condoms was claimed by 31% of the heterosexually-transmitted women before the HIV test, and by 74% (P = 0.002) after the test. In 1988 73% of the women tested HIV positive were infected by heterosexual contact, in 1985 only 14%. We conclude that among HIV infected women in Copenhagen heterosexual transmission is a problem. These women seem to change sexual behaviour when informed about HIV positivity. PMID- 2094404 TI - Discriminant attitudes and beliefs about condoms in young, multi-partner heterosexuals. AB - Four hundred and eight people aged 15-35 years who reported having more than one sexual partner of the opposite sex in the past year or who thought it likely that they would do so in the next year were surveyed about their sexual behaviour, concern about acquired immunodeficiency syndrome and sexually transmitted diseases and attitudes to condom use. Differences in concerns and attitudes between regular and non- or irregular condom users and between men and women are reported. Three conceptually coherent factors (condom use as positive action; condom use as cue to embarrassment; and condom use as antithetical to good sex) discriminated between users and non-users. Implications for health promotion campaigns designed to promote condom use are discussed. PMID- 2094405 TI - Aetiology of non-gonococcal urethritis: a possible relation to other infections. AB - Chlamydia trachomatis can be identified in up to 60% of cases of nongonococcal urethritis (NGU) and the aetiology of most of the remainder is obscure. This paper reports a role for other genitourinary (GU) infections such as candidiasis, warts and herpes simplex, in the causation of NGU. One hundred and ten men fulfilled the entry criteria which included the probability that their contacts would attend the department. Fifty-four of the 110 men had GU infections other than NGU; 56 had no other infections. NGU was detected in 31 (57%) of cases with other GU infections and 8 (26%) were chlamydiae-positive: in contrast NGU was found in only 10 (18%) of those with none of the other infections and 3 (30%) were chlamydiae-positive. Chlamydiae-negative NGU was, therefore, more common in those with other GU infections. Forty-five (86%) of 52 contacts of 41 patients with NGU had various GU infections such as candidosis and anaerobic vaginosis, in contrast with other GU infections in only 7 (23%) of 30 contacts of men with no other GU infections. Other GU infections in patients and their contacts appeared significantly related to the presence of chlamydiae-negative NGU. PMID- 2094406 TI - Reasons for non-use of condoms by homosexually active men during anal intercourse. AB - Sixty-eight homosexually active men attending an STD clinic were questioned to ascertain the percentage of the time they did not use condoms during anal intercourse, and the reasons for this. Data indicated that the reasons most commonly given were being in a steady relationship (32.8%), being unprepared (19.4%), couldn't be bothered (19.4%), use of alcohol or drugs (7.5%), being bisexual (4.5%), attractiveness of partner or partner attitude toward sex, and knowing the partner (3% each). These data suggest that both trust and situational variables are barriers to consistent condom use in homosexually active men. PMID- 2094407 TI - Neuropsychological and psychiatric changes following treatment of ARC patients with zidovudine. AB - Six homosexual men with a diagnosis of acquired immunodeficiency syndrome (AIDS) related complex (ARC- CDC IVA/C2) were assessed with a series of neuropsychological and psychiatric tests prior to commencing treatment with zidovudine and again after 5-6 months. Significant improvements were seen in cognitive functioning, mental state and physical health at the second assessment. PMID- 2094408 TI - Syphilis serology and human immunodeficiency virus positivity in Chandigarh. AB - AIDS and other sexually transmitted diseases are interlinked. VDRL positivity may indicate that the individual has an increased risk of being HIV positive as the epidemiological risk factors for developing syphilis and AIDS are similar. We analysed 323 (5.8%) VDRL positive serum samples (out of 5592 screened) for HIV positivity. All were HIV negative. While syphilitic infection in India at present is not commonly associated with HIV infection, experience in other countries indicates caution. PMID- 2094409 TI - Personal reminiscences of a venereologist before penicillin. PMID- 2094410 TI - Feigned HIV disease. PMID- 2094411 TI - Oral contraceptive use and HIV infection. PMID- 2094412 TI - AIDS Literature Index. PMID- 2094413 TI - Cyclodextrin chiral stationary phases for liquid chromatographic separations of drug stereoisomers. AB - Many active drugs are racemic mixtures. Because the two enantiomers of a racemate often cause different pharmacological responses, the use of optically pure isomers is desirable and may be soon required. Cyclodextrin-bonded silica gel can be used as chiral stationary phase (CSP) in liquid chromatography. The enantiomers of 25 different racemic drugs were separated on such CSPs in the reversed-phase mode. The principal features of the cyclodextrin chiral recognition mechanism are recalled and some information on future trends for cyclodextrin CSPs is provided. PMID- 2094414 TI - Electroanalytical approaches to understanding benzene metabolism. AB - Electrochemical techniques are ideally suited to the study of the metabolism of aromatic xenobiotics because the metabolites are frequently easier to oxidize than the parent compounds. In many cases, the trace metabolites have the lowest oxidation potentials and hence electrochemical methods have the greatest selectivity for these compounds. The sensitivity of dual-electrode liquid chromatography-electrochemistry for the detection and identification of trace metabolites was demonstrated by the detection of the secondary metabolite, hydroquinone, in a microsomal incubation containing benzene and ascorbic acid. The use of an electrochemical detector in a series configuration provides increased selectivity for chemically reversible metabolites such as hydroquinone. Electrochemical methods can also be used to generate metabolites. The products of the electrochemical oxidation of phenol and biphenol are compared with those generated in a peroxidase incubation. PMID- 2094415 TI - Electrochemical investigations of immunologically reactive procainamide metabolites. AB - As a result of the implication of N-oxidized procainamide metabolites in drug related lupus (DRL), the electrochemical behaviour of these compounds was investigated and a coulometric synthesis of the nitroso derivative developed using a previously described carbon packed bed bulk electrolysis flow cell. The electrochemical characterization of the parent p-substituted aromatic amine and the N-oxidized derivatives was achieved through systematic comparison with previously well described aromatic amine and nitro systems using cyclic voltammetry and liquid chromatography with electrochemical detection (LC-EC). Chromatographically assisted hydrodynamic voltammetry indicated current limiting plateau potentials of 0.45 and -0.2 V versus Ag/AgCl, respectively, for synthetically prepared procainamide hydroxylamine and electrolytically prepared nitrosoprocainamide. Reaction characterization and binding behaviour is described for each of the procainamide metabolites following in vitro incubations with cysteine, glutathione, ascorbic acid and mouse haemoglobin. PMID- 2094416 TI - Determination of the anticancer drug, 15-deoxyspergualin, in plasma ultrafiltrate by liquid chromatography and precolumn derivatization with naphthalene-2,3 dicarboxaldehyde/cyanide. AB - An alternative analytical method for the determination of 15-deoxyspergualin in plasma is described. The drug was initially separated from the plasma matrix by ultrafiltration and a precolumn derivatization step was performed with naphthalene-2,3-dicarboxaldehyde in the presence of sodium cyanide to yield the fluorescent N-substituted 1-cyanobenz[f]isoindole (CBI) derivative. The CBI derivative was separated and quantitated by reversed-phase chromatography using an ODS Hypersil column and mobile phase of KH2PO4 (0.1 M)-H3PO4-acetonitrile (48:0.8:52, v/v/v) containing dodecyl sodium sulphate (18 mM). The excitation and emission wavelengths for the fluorescence detector were 420 and 490 nm, respectively. The peak height was linearly related to drug concentration over the range from 5 ng ml-1 (10 nM) to 10 micrograms ml-1 (20 microM) in phosphate buffer (0.1 M, pH 7.0), spiked plasma ultrafiltrate and ultrafiltrate obtained from spiked plasma. Measurements could be made with a relative standard deviation of 4.5% or less in phosphate buffer (0.1 M, pH 7.0), 6.1% or less in spiked plasma ultrafiltrate and 12% or less in ultrafiltrate obtained from spiked plasma. PMID- 2094418 TI - Novel strategies for clinical drug analysis with new column technology in liquid chromatography. AB - Clinical drug analysis has been the focus of much attention and controversy because of the increase in substance abuse testing of addicts, patients, employees and others, in addition to the rapidly growing fields of therapeutic drug monitoring and clinical toxicology. This review focuses on the latest methodological and technological advances in liquid chromatography (LC) as it is applied to clinical drug analysis. Based on the author's experience, key chromatographic parameters such as carbon load, functionalities and temperature are proposed for the separation of structurally similar metabolites and for resolving chromatographic interferences by other drugs and metabolites. Novel sample preparation for cyclosporine and gradient elution of its metabolites are reviewed, followed by an update on monitoring of 3'-azido-3'-deoxythymidine with emphasis on automated sample preparation. Various approaches of direct sample analysis are advocated for increased efficiency as a result of minimal sample preparation and potential advantages such as decreased exposure of personnel to infectious samples. An update of microbore LC indicates that 2-mm columns may be readily used for clinical paediatric and neonatal analysis without dedicated chromatographs. Potential applications of multidimensional-multimodal chromatography include analyses of a cocaine impurity, anticonvulsants, antidepressants, and five ingredients of a common cold medication. PMID- 2094417 TI - Application of liquid chromatography with on-line radiochemical detection to metabolism studies on a novel class of analgesics. AB - Vanilloids are a class of compounds structurally related to capsaicin, the pungent principle of hot peppers, which are under development as a novel class of analgesics. Vanilloids undergo extensive first-pass metabolism when dosed orally to rats and mice. These compounds, as well as capsaicin, would be anticipated to be susceptible to three major routes of metabolism: (omega, beta)-oxidation of the alkyl side chain, hydrolysis of the amide bond and conjugation of the phenolic group. Olvanil [N-(3-methoxy-4-hydroxybenzyl)oleamide], radiolabelled with either 14C at the benzylic carbon or 3H in the oleyl side chain, was studied in various in vitro, in situ and in vivo metabolism models to determine the major route(s) of intestinal and hepatic metabolism in rats for this new class of compounds. Models used in metabolism studies included isolated hydrolytic enzymes, cell-free intestinal and liver supernatants, hepatocytes, enterocytes, perfused intestine and whole animal studies. Reversed-phase liquid chromatography (LC) with on-line radiochemical detection was used to examine the metabolic profiles from the different models. The major metabolic route for olvanil in both the intestine and the liver was found to be hydrolysis of the amide bond. The benefits of selective 14C and 3H labels in conjunction with LC with on-line radiochemical detection are discussed. PMID- 2094419 TI - On-line mass spectrometric investigation of the peroxidase-catalysed oxidation of uric acid. AB - The enzymatic and electrochemical oxidation pathways of uric acid were determined on-line with thermospray-tandem mass spectrometry. Products and intermediates formed as a result of electrooxidation were monitored as the electrode potential was varied. Electrochemical results served as a model for the enzymatic studies. In fact, electrochemical studies were essential for elucidating the structures of intermediates because of the high conversion efficiencies in electrooxidation. Products and intermediates formed as a result of enzymatic oxidation of uric acid were monitored as the reaction time was varied. When the enzymatic oxidation of uric acid with peroxidase and H2O2 was studied, the same intermediates and products were observed as in the electrochemical oxidation. The tandem mass spectrometric results provide convincing evidence that the primary intermediate produced during both the enzymatic and electrochemical oxidation of uric acid has a quinonoid diimine structure. The primary intermediate can follow three distinct reaction pathways to produce the identified final products. The final enzymatic and electrochemical oxidation products observed in these studies were urea, CO2, alloxan, alloxan monohydrate, allantoin, 5-hydroxyhydantoin-5-carboxamide and parabanic acid. PMID- 2094420 TI - Multicomponent spectrophotometric assay of riboflavine and photoproducts. AB - A multicomponent spectrophotometric method has been developed for the simultaneous determination of riboflavine, formylmethylflavine and degradation products in photolysed solutions. It is based on partial separation of the photoproducts by chloroform extraction at pH 2.0 in a potassium chloride hydrochloric acid solution and subsequent determination, in the aqueous phase, of riboflavine and formylmethylflavine at 445 and 385 nm. The chloroform extract containing lumichrome and lumiflavine is evaporated to dryness, the residue dissolved in acetate buffer (pH 4.5) and the products determined at 356 and 445 nm. The reproducibility of the method, based on the analysis of synthetic mixtures, is within +/- 5%. Absorption corrections for minor products and interfering substances have been proposed. Chromatographic, spectrophotometric and distribution coefficient data for riboflavine and photoproducts are reported. The method is specific, rapid and convenient for photodegradation studies of riboflavine and formylmethylflavine. PMID- 2094421 TI - Differential pulse polarographic assay of tolmetin sodium capsules. AB - Differential pulse polarography (DPP) is proposed as a direct method for the quantitation of tolmetin sodium in a capsule formulation (Tolectin--200 mg as the sodium dihydrate salt). Classical direct-current (DC) polarography has been employed to investigate the nature of the reduction occurring at the surface of the dropping mercury electrode (DME) using acetate buffer of pH 5.0 as the supporting electrolyte. The mean value of the results obtained by DPP expressed as a percentage of the stated amount, and the standard deviation, were found to be 99.87 +/- 0.43. The standard addition procedure used to assess the accuracy of the proposed method gave a mean percentage recovery of the total drug of 100.15 +/- 0.75%. PMID- 2094422 TI - Chemometric study and analytical enzymatic methods for diagnosis of cholesterol gallstones. AB - The lithogenic index (IL) provides an estimate of cholesterol saturation in gallbladder bile and is of possible value for prediction of gallstone formation. A package for pattern recognition of analytical chemical data, known as "Parvus", was used to study the different values of IL obtained experimentally using common enzymic methods for cholesterol and bile salts and other analytical techniques for phospholipids. Ten patients were investigated and some interesting conclusions were drawn, both on the equivalence of various analytical methods for the determination of phospholipids and on the contribution of pattern recognition analysis to the diagnosis of gallstones. PMID- 2094423 TI - Group separation of free and conjugated bile acids by pre-packed anion-exchange cartridges. AB - A rapid and simple procedure for the group separation of the major free and conjugated bile acids of man is described. After initial extraction with Bond Elut C18 cartridges, the analytes are fractionated into the unconjugated, glycine and taurine-conjugated forms using disposable Bond Elut SAX columns and methanol acetate buffer eluents. The method is found to be accurate and reproducible and to afford complete resolution between fractions. Free and conjugated bile acids present in human bile and gastric juice are assayed by high-performance liquid chromatography, after extraction and group separation according to the described procedure. PMID- 2094424 TI - Rapid determination of benzalkonium chloride in pharmaceutical preparations with flow injection liquid-liquid extraction. AB - Benzalkonium chloride was assayed by on-line extraction of the benzalkonium ion with picrate to chloroform. The absorbance of picrate was measured. The extractions were performed with a home-made flow injection extraction unit. Calibration curves (1.5-180 x 10(-4)% w/v) were straight lines (r = 0.9993) and the relative standard deviation of a series of injections was less than or equal to 2%. Pharmaceutical benzalkonium preparations, containing xylometazoline, timolol, phenylephrine or carbachol could also be assayed. The method was compared with a modified HPLC assay. PMID- 2094425 TI - Importance of enantiomeric purity and its control by thin-layer chromatography. AB - Methods for the direct resolution of enantiomers are important and are necessary for pharmaceutical and biomedical analysis, synthetic and mechanistic studies and various other fields. The present paper deals with the results of recent approaches, such as ligand exchange, ion exchange and steric interactions, providing direct resolution of enantiomers of a variety of compounds by thin layer chromatography. General aspects of various methods for analysis of enantiomeric purity and resolution have been compared. PMID- 2094426 TI - Evaluation of a photodiode array detector for the verification of peak homogeneity in high-performance liquid chromatography. AB - Photodiode array liquid chromatography detectors are claimed to have the ability of evaluating the homogeneity of chromatographic peaks and this could provide a very powerful tool in support of method development. However, in pharmaceutical analysis, for this to be of practical value it must be capable of detecting inhomogeneities at low levels. In this paper, a test has been devised to challenge the sensitivity of instruments to this application. The test makes use of mixtures of the similar benzodiazepines temazepam and lormetazepam in a chromatographic system which does not separate them. One instrument has demonstrated the ability to detect levels of just 0.5% w/w of one benzodiazepine in the other. Statistical F-tests and t-tests have been used to demonstrate that non-homogeneities have been detected with a high level of confidence. It is concluded that photodiode array detectors have the potential to evaluate the homogeneity of chromatographic peaks with a high degree of sensitivity. However, most instruments do not realize this potential because their software does not make proper use of all the data available. PMID- 2094427 TI - Comparison of serum hydroquinidine determination by fluorescence polarization immunoassay and liquid chromatography. AB - Hydroquinidine is a structural analogue of quinidine. It is used in the treatment and prevention of cardiac arrhythmias and necessitates serum monitoring. Fluorescence polarization immunoassay (FPIA) of quinidine has been proposed and we have tested the performance of this assay for hydroquinidine using its cross reaction with quinidine. Tracer (quinidine labelled with fluorescein) and anti serum were purchased from Abbott S.A. Standard curves were obtained using specifically prepared hydroquinidine calibrators and within-run and run-to-run precision values (expressed as relative standard deviation) (RSD) lower than 5.3% (n = 10). In order to evaluate specificity of this assay in the clinical situation, FPIA and liquid chromatography results were compared. PMID- 2094428 TI - Determination of imipenem in human plasma, urine and tissue by high-performance liquid chromatography. AB - A simple and reliable HPLC method is described for the new beta-lactam antibiotic imipenem; suitable extraction procedures for the drug in human plasma, urine and prostatic tissue are described. The figures of merit for the assays are reported and examples given of their application. PMID- 2094429 TI - Spectrophotometric determination of some antiallergic agents with 3-methyl-2 benzothiazolinone hydrazone. PMID- 2094430 TI - Determination of sorbitan trioleate in metered-dose inhalers by supercritical fluid chromatography. PMID- 2094431 TI - Improved preparation and structural conformation of the fluorescence labelling reagents 1,2-diamino-4,5-dimethoxybenzene and 3,4-dihydro-6,7-dimethoxy-4-methyl 3-oxo-quinoxaline-2-carbonyl chloride. PMID- 2094432 TI - Monoclonal antibody in the identification of Haemophilus somnus. AB - Electrophoretic comparisons of outer membrane proteins of Haemophilus somnus isolates revealed 2 major protein bands (46 and 14 kilodaltons [kD]) common to all isolates tested. A monoclonal antibody raised against H. somnus reacted to the 46-kD band. Coagglutination tests were performed using a monoclonal antibody coagglutination assay. The monoclonal reagent was produced by incubating Cowan strain Staphylococcus aureus suspension, used as a source of crude protein A, with mouse ascitic fluid monoclonal antibody or goat anti-H. somnus hyperimmune serum. Bacteria to be tested were suspended at a concentration of 4.5 x 10(9) cells/ml. The coagglutination test was performed by the addition of 50 microliters of the monoclonal reagent to 50 microliters of the bacterial suspension on a glass plate and manual rotation for 2-3 minutes. The coagglutination assay using Cowan strain Staphylococcus aureus protein A, coupled with the monoclonal antibody, agglutinated 10 different H. somnus isolates. The antibody reagent did not coagglutinate with Actinobacillus suis, A. equuli, Pasteurella haemolytica, P. multocida, or P. pneumotropica under similar test conditions. PMID- 2094433 TI - Diagnosis of bromethalin toxicosis in the dog. AB - Dogs given a single oral dose of bromethalin at 6.25 mg/kg developed a toxic syndrome characterized by hyperexcitability, tremors, seizures, depression, and death within 15-63 hours after bromethalin administration. Gross lesions included mild cerebral edema (2/5) and mild pulmonary congestion (2/5). Histologic lesions included diffuse white matter spongiosis (5/5), mild microgliosis (3/5), optic nerve vacuolization (3/5), mild thickening of Bowman's capsule (2/5), and occasional splenic megakaryocytes (2/5). Ultramicroscopic examination of midbrain stem revealed occasional swollen axons, intramyelinic vacuolization, and myelin splitting at the intraperiod line. Bromethalin was detected in kidney, liver, fat, and brain tissues, using gas chromatography with electron capture detection. Photodegradation of extracted bromethalin may limit accurate quantification of tissue residues. PMID- 2094434 TI - Hexachlorophene toxicosis in a litter of Doberman pinschers. AB - A litter of 5-week-old Doberman Pinschers with pustular dermatitis was treated dermally with a hexachlorophene-containing emulsion. Shortly after a second treatment, all of the puppies developed neurologic signs consisting of muscle tremors, ataxia, and apparent muscle weakness. The clinical history and signs, histologic lesions within the central nervous system, and measurement of hexachlorophene in liver and kidney tissue confirmed a diagnosis of hexachlorophene toxicosis. PMID- 2094435 TI - A high-performance liquid chromatography method for determination of 4 aminopyridine in tissues and urine. AB - An analytical method was developed to measure 4-aminopyridine in tissues and urine to determine appropriate diagnostic samples in acute poisoning cases. Tissues from rats dosed with 4-aminopyridine were extracted with methylene chloride. Extracts were analyzed by high-performance liquid chromatography using an isocratic solvent system of acetonitrile and aqueous solution (15/85 v/v) consisting of 0.015 M sodium salt of l-heptane-sulfonic acid, 0.002 M tetramethylammonium bromide, and 0.01 M sodium dihydrogen phosphate adjusted to pH 3.0 with phosphoric acid. We concluded that suitable diagnostic samples for acute poisoning cases include stomach contents, kidney, liver, and urine. PMID- 2094436 TI - An unusual case of traumatic pericarditis in a cow. PMID- 2094437 TI - Bovine bacillary hemoglobinuria (Clostridium haemolyticum) in Iran. PMID- 2094438 TI - Eosinophilic encephalomyelitis in a raccoon experimentally infected with a dog isolate of rabies virus. PMID- 2094439 TI - The effect of heat-inactivation on agglutinating antibody titers to Leptospira interrogans. PMID- 2094440 TI - A quantitative, automated method for determining microbial resistance to complement. PMID- 2094441 TI - Performance studies of an enzyme-linked immunosorbent assay for detecting Staphylococcus aureus antibody in bovine milk. AB - An enzyme-linked immunosorbent assay (ELISA) for detecting Staphylococcus aureus antibody in bovine milk samples was examined for repeatability. A set of 51 bovine milk samples from 4 universities with confirmed culture results was assembled, and a panel of 30 milk samples was randomly selected. When the selected panel was tested at the collection laboratory, there was 97% agreement between the ELISA and the culture test. The panel was tested with the ELISA by the 4 university laboratories. Results were scored by both visual and optical density reader methods. When compared to reference ELISA results, the university laboratory ELISA results showed an agreement of 99.8% for negative samples, 98% for positive samples, and 99% for all samples. Additional studies on 19 milk samples that cultured positive for bacteria other than S. aureus showed 100% specificity. Overall comparison of ELISA and culture results showed high agreement between the 2 techniques. Disagreement appeared to result from explainable differences in antibody and bacterial levels and not from errors in either of the 2 techniques. PMID- 2094442 TI - Isolation of Gardnerella vaginalis from the reproductive tract of four mares. AB - A gram-variable pleomorphic bacillus was isolated from the reproductive tracts of 4 mares during routine prebreeding soundness examinations. Using a commercial bacterial identification system, these organisms were identified as Streptococcus acidominimus. However, colonial and Gram-staining characteristics did not support this identification. Subsequent testing indicated the organism was similar to Gardnerella vaginalis. Additional growth and biochemical analysis performed in our laboratory and at the Michigan Department of Public Health and by the Center for Disease Control, Atlanta, Georgia, confirmed the identification of G. vaginalis. PMID- 2094443 TI - Porcine leptospirosis in Iowa. AB - The epidemiology of leptospirosis in Iowa swine was examined on the basis of serologic results and herd data from 55 herds in the National Animal Health Monitoring System (NAHMS) program and culture results and histories from 578 cases of reproductive failure submitted to the Iowa Veterinary Diagnostic Laboratory during a 3-year period. Thirty-eight percent of sera from NAHMS herds contained antibodies against 1 or more of 12 leptospira antigens. Leptospires were isolated from 9 (1.6%) of 578 cases of reproductive failure. Seven (78%) of the isolates were identified as Leptospira interrogans serovar kennewicki and 2 (22%) as serovar grippotyphosa. In 7 herds from which leptospires were isolated, attack rates ranged from 1% to 84%. Clinical leptospirosis, characterized by reproductive failure and confirmed by isolation of leptospires, was sporadic. No significant differences in farrowing averages and reproductive problems were observed between vaccinated and nonvaccinated NAHMS herds or between herds with higher (43-63%) or lower (14-40%) percentages of animals that were serologically positive against serovar bratislava. PMID- 2094444 TI - Comparison of a radioimmunoprecipitation assay to immunoblotting and ELISA for detection of antibody to African swine fever virus. AB - A radioimmunoprecipitation assay (RIPA) has been developed for detection of antibody to African swine fever virus (ASFV) and compared with the immunoblot assay with regard to sensitivity and specificity. Two hundred seven field sera, obtained from pigs in Spain from different geographic areas between 1975 and 1986, that were positive by ASFV enzyme-linked immunosorbent assay (ELISA) were also analysed by immunoblot assay and RIPA. By serum dilution experiments, the RIPA appeared at least as sensitive as the ELISA and immunoblotting tests, although ELISA and RIPA detected antibodies to ASFV earlier in natural infection than did the immunoblot assay, as disclosed by animal inoculation studies. The most antigenic ASFV-induced proteins in natural infection detected by RIPA were the viral proteins p243, p172, p73, p25.5, p15, and p12 and the infection proteins p30 and p23.5. In the immunoblot assay, the proteins that were most reactive with the same sera were the viral protein p25.5 and the infection proteins p30, p25, and p21.5. Only 1 serum, from an animal infected with ASFV, was negative by immunoblot assay but showed a positive result by RIPA. A modification of conventional RIPA was performed using a dot transference of immunoprecipitated proteins to a nitrocellulose filter. This modification simplified the conventional RIPA procedures by eliminating the electrophoresis of immunoprecipitated proteins without affecting sensitivity and specificity. The ease of use, specificity, and the sensitivity comparable to that of the immunoblot assay make the RIPA a useful confirmatory assay for sera that yield conflicting results in other ASFV antibody assays. PMID- 2094445 TI - Extracutaneous viral inclusions in psittacine beak and feather disease. AB - Thirty-five birds that died with naturally acquired psittacine beak and feather disease (PBFD) were necropsied to identify extracutaneous viral inclusions. Inclusions were found in various tissue sections from 34 of 35 birds. By immunoperoxidase staining, intranuclear and intracytoplasmic inclusion bodies were shown to contain PBFD viral antigen. Inclusion-bearing lesions were widely disseminated but often closely associated with the alimentary tract. Lesions within the palate, esophagus, crop, intestine, bursa of Fabricius, and liver probably serve as sources for viral shedding into the feces. PMID- 2094446 TI - Laboratory findings associated with abomasal ulcers/tympany in range calves. AB - The etiology of abomasal ulcers/tympany was investigated in 48 animals from 36 ranches in Wyoming and Nebraska. Results indicate that subclinical trace mineral deficiencies of copper and/or selenium exist in the range cattle in west central Nebraska and Wyoming. Etiological agents most frequently incriminated by bacteriologic cultures and/or histopathic examination were Clostridium perfringens and Campylobacter species. Histopathologic evaluation of abomasums revealed 31 of 38 cases contained abundant gram-positive bacteria associated with the damaged abomasal mucosa. Campylobacter-like organisms were demonstrated in 9 of 38 cases using the modified Dieterle stain. Clostridium perfringens was isolated in 14 of 38 cases, and Campylobacter jejuni was recovered from 5 of 38 cases. PMID- 2094447 TI - Fumonisin B1 levels associated with an epizootic of equine leukoencephalomalacia. AB - During the fall of 1989, an episode of equine leukoencephalomalacia involved 18 of 66 purebred Arabian horses at a breeding/training stable in Arizona. Of the 18 horses affected, the condition was fatal in 14. These horses, as well as 48 unaffected horses, had been fed a diet containing a substantial amount of white corn screenings. Gross pathologic findings included liquefactive necrosis in parts of the cerebral white matter and hemorrhagic foci of various sizes in the brain stem. Histopathologic findings included rarefied white matter with pyknotic nuclei and eosinophilic cytoplasm. Thin-layer chromatography, high-performance liquid chromatography, and gas chromatography/mass spectroscopy were utilized to identify and quantitate fumonisin B1 in 3 samples of corn from the farm. Concentrations of fumonisin B1 range from 37 to 122 ppm. Fumonisin B2 was also detected. Using information on diet, animal weights, and feeding practices, estimates of total fumonisin B1 dosage were determined. This is the first definitive report on equine leukoencephalomalacia and associated fumonisin B1 concentrations. PMID- 2094448 TI - Pulmonary edema and hydrothorax in swine produced by fumonisin B1, a toxic metabolite of Fusarium moniliforme. AB - Pulmonary edema and hydrothorax were observed in mature swine that died approximately 5 days after consuming corn screenings. These postmortem observations were reproduced in younger swine (16-24 kg) that died within 1 week when fed the corn screenings under experimental conditions. Additionally, pulmonary edema and hydrothorax occurred in a pig (7.1 kg) that died after receiving 4 daily intravenous injections of fumonisin B1. A fungus was isolated from the corn screenings that is identical to Fusarium moniliforme MRC-826 in colony morphology and under microscopic examination. PMID- 2094449 TI - Lead concentrations in blood and milk from periparturient dairy heifers seven months after an episode of acute lead toxicosis. AB - In September 1988, 100 of 300 yearling dairy heifers developed blindness, tachypnea, foaming at the mouth, chewing, and facial fasciculations. Twenty-five animals died. Lead toxicosis was diagnosed based on the clinical signs and the presence of excessive concentrations of lead in whole blood, liver, kidney, and rumen contents of affected animals. The source of the lead was sudan grass silage that had been contaminated by soil that contained up to 77,000 mg/kg of lead. Lead concentrations were determined approximately 7 months after the acute episode of lead toxicosis. Whole blood and milk samples were obtained from heifers and a group of control cows 2 weeks prior to (blood only), at the time of, and 2 and 4 weeks after freshening. No lead was found in any of the milk samples (detection limit = 0.055 mg/liter). Animals that had been severely affected by lead toxicosis experienced a transient increase in whole blood lead concentrations at freshening that was not high enough to be considered toxic. No similar increases in blood lead were observed for control cows or heifers that had experienced milder toxicosis. These findings suggest that at parturition lead is mobilized into the blood of cattle previously exposed to excessive lead. PMID- 2094450 TI - Cutaneous ulceration and necrosis in pigs fed aflatoxin- and T-2 toxin contaminated diets. PMID- 2094451 TI - Acute iron intoxication in a herd of young bulls. PMID- 2094452 TI - Neospora caninum induced abortion in sheep. PMID- 2094453 TI - Fatal encephalitis in a dog associated with an unidentified coccidian parasite. PMID- 2094454 TI - Asymptomatic salmonellosis in healthy adult horses. PMID- 2094455 TI - Isolation of Campylobacter coli from a proliferative intestinal lesion in a ferret. PMID- 2094456 TI - Tularemia in a cat. PMID- 2094457 TI - An update on Streptococcus suis identification. PMID- 2094458 TI - Pregnancy in continuous ambulatory peritoneal dialysis (CAPD) patients. PMID- 2094459 TI - Continuous ambulatory peritoneal dialysis (CAPD) or center hemodialysis? Retrospective evaluation of the success of both methods. AB - In a retrospective study, the authors analysed the dialysis-technique success rate in 276 chronic renal patients. Of these, 137 patients have been treated with in center hemodialysis (CHD) from 1972 to 1989 and 139 with continuous ambulatory peritoneal dialysis (CAPD) from 1978 to 1989. The six-year technique success rate was 28% in CAPD and 31% in CHD (statistically not significantly different). Various risk factors influence the technique-success rate of both methods in the same way. The results suggest that in our center CAPD is as effective as CHD in the treatment of patients with end-stage renal failure. PMID- 2094460 TI - Recombinant human growth hormone (rhGH) treatment of children undergoing peritoneal dialysis. AB - The authors studied the effect of recombinant growth hormone (rhGH) treatment on 5 growth retarded children, age 2 2/12 to 17 8/12 years, who had end-stage renal disease (ESRD) and were undergoing continuous cycling peritoneal dialysis (CCPD). Patients received 0.125 mg/kg of subcutaneous rhGH 3 times weekly. Accelerated height velocity compared to the previous year of CCPD was noted in 2 patients and improvement in the standard deviation score (SDS) as a parameter of improved growth velocity was noted in a third patient. This was associated with an increase in weight and improvement in the midarm muscle circumference (MAMC) suggesting an anabolic effect of rhGH treatment. Bone age advancement was consistent with the period of observation; no advancement greater than that expected for the increase in chronological age was observed. No significant side effects were attributable to rhGH therapy. These preliminary results indicate some growth retarded children without growth hormone deficiency with ESRD undergoing CCPD may respond to exogenous rhGH therapy with an acceleration in growth velocity: However, the failure to achieve uniform acceleration of height velocity indicates the need for controlled studies before rhGH can be recommended for all growth retarded children with ESRD undergoing peritoneal dialysis. PMID- 2094461 TI - Continuous ambulatory peritoneal dialysis (CAPD) of children with amino acid solutions: technical and metabolic aspects. AB - The changes in plasma and dialysate amino acids (AA) in 7 continuous ambulatory peritoneal dialysis (CAPD) children after dialysis with a 1% AA solution were compared with a glucose-containing solution. During the AA-exchange, the plasma levels of individual AA reached their peaks after 1 h, with their percentage increments significantly correlated (p less than 0.001) with the ratio of the amount of AA in the bag to the basal plasma concentration. The plasma concentration of methionine, valine, phenylalanine, and isoleucine remained higher than the basal value at 4 h. The amount of AA absorbed was 66% after 1 h, and 86% after 4 h and 6 h, corresponding to 2574 +/- 253 mumol/kg body wt. During glucose-dialysis (1.36%), levels of histidine, methionine, valine, phenylalanine, and isoleucine were significantly decreased in plasma after 1 h, and stayed low throughout the dialysis period. The loss of AA with the peritoneal effluent was 116 +/- 69 mumol/kg/body wt. From this study, it seems that using an AA dialysis solution, with 1 exchange per day, might limit the daily glucose load and compensate for AA losses by supplying an extra amount of AA and by reducing the loss of other AA not contained in dialysis solutions. The AA pattern in plasma following AA-dialysis resembles that observed after a protein meal, with no signs of persistently high, nonphysiological levels. PMID- 2094462 TI - An outpatient maneuver to treat bloody effluent during continuous ambulatory peritoneal dialysis (CAPD). AB - Asymptomatic episodes of grossly bloody effluent during continuous ambulatory peritoneal dialysis (CAPD) can be treated by following a simple therapeutic maneuver. The patient performs one to three rapid exchanges using unwarmed (room temperature), 1.5% dextrose-containing dialysate. No dwell time is employed. This treatment proves successful in a variety of clinical settings, and no adverse effects have been noted. Infusion of unwarmed dialysate likely induces peritoneal vasoconstriction and thus favors hemostasis. Bleeding of nonperitoneal etiology, such as renal cyst hemorrhage or retrograde menstruation, proves resistant. PMID- 2094463 TI - The curled catheter: dependable device for percutaneous peritoneal access. AB - The curled peritoneal dialysis catheter is theoretically less prone to catheter migration and drainage failure. It also allows percutaneous placement, rather than surgical placement exclusively, whenever desired or necessary. Review of 213 curled-catheter placements, 134 (63%) percutaneous and 79 (37%) surgical, over the last 4 years, shows that the probability of continuing catheter function by life-table analysis was 88% at one year, 71% at 2 years, and 61% at three years, with no difference comparing percutaneous to surgical placement. Among the 213 total cases, nearly 50% of all catheters were still functioning at last follow up, and 38 catheters (17.8%) have been lost in total, attributed to infectious complications in 24 cases (tunnel-exit infection alone in 5, peritonitis alone in 11, combined infection in 8), refractory drain failure in 9 cases (early drain failure in 4, late drain failure in 5), recurrent late subcutaneous dialysate leaking in 3 cases, and peri-catheter hernia in 2 cases. Among other complications, the incidence of early drain failure (7.0%), and late drain failure (4.2%), compare favorably to reports describing other devices or other placement methods having comparable size of reported experience. Analyzing our own percutaneous and surgical placements separately, there were no differences in the respective frequencies of early drain failure, late drain failure, late subcutaneous dialysate leaking, outer cuff extrusion, required hernia repair, peritonitis or tunnel-exit infection. Only early external dialysate leaking was more frequent using percutaneous placement methods (21.6% vs. 10.1%; p less than 0.05), although no catheters were lost due to early external leaking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094464 TI - Peritoneal calcification in a peritoneal dialysis patient: a case report. AB - A case of peritoneal calcification in a 44-year-old female treated with peritoneal dialysis for 13 years is reported. The patient, who had secondary hyperparathyroidism and had suffered repeated episodes of catheter-related peritonitis, presented with intraperitoneal bleeding and underwent laparotomy and excision of some of the calcified peritoneal plaques. She remains well on peritoneal dialysis 1 year later with occasional mild intraperitoneal bleeding and reduced peritoneal filtration. PMID- 2094465 TI - Cost analysis of peritoneal catheter infections. PMID- 2094467 TI - Lymphatic absorption in continuous ambulatory peritoneal dialysis (CAPD) PMID- 2094466 TI - Peritoneal dialysis in the treatment of severe poisoning with organophosphorous pesticides: experience with twenty-two patients. PMID- 2094468 TI - Extreme dialysate dumping as a cause of inadequate dialysis in continuous ambulatory peritoneal dialysis (CAPD) PMID- 2094469 TI - Use of prophylactic antibiotics in lower gastrointestinal endoscopy. PMID- 2094471 TI - Literature. July-September 1990. PMID- 2094470 TI - Poodle peritonitis. PMID- 2094472 TI - Skin expansion--a sword that "stretches" two ways: scalp expansion and bone erosion. AB - Tissue expanders, which are used to enlarge the soft tissue of the scalp, eroded the outer table of the skull as well as a portion of the inner table. The patient in this case study is documented with photographs, and the entity of pressure due to skin expanders is discussed. A growing list of complications makes it important to be aware of the possible pitfalls of expanders and to discuss them with patients and/or their families, particularly when tissue expanders are used in children. PMID- 2094474 TI - Statistical investigation of mandibular dimensions for the planning of a series of mandibular corpus replacements. AB - The mandibular corpus height, the width measured at the height of the foramina mental and at a distance of 3 mm from the base, the mandibular corpus length and the mandibular angle were examined in 368 (185 male, 167 female, and 34 uncertain) intact, European anthropologic skulls. The differences between the left and right sides and the two sexes were evaluated. No significant difference was found between the two sides. The differences between males and females did prove statistically significant, but was considered unimportant with regard to the aim of planning a series of mandibular prostheses. The experimental data were broken down into five classes, and the class medians were taken to be the dimensions for the replacements. For a five-piece series, the relative percentage distribution of the class medians suggests the following proportions for production (mean -2SD and mean +2SD 6%, mean -SD and mean +SD 25% and mean 38%). Mandibles with these average dimensions can be chosen from the anthropologic collection, wax models of which may facilitate the planning of a series of mandibular corpus prostheses. PMID- 2094473 TI - Vascular lesions involving the cranial base: combined surgical and interventional radiologic approach. AB - Advantages and possible complications of combined surgical and interventional radiologic approach to vascular lesions involving the cranial base are presented in three case examples. The methodology and technology of endovascular embolization and occlusion techniques, selection of embolic materials, functional testing to prevent neurologic injury and surgical implications of these treatment modalities are discussed. Emphasis is placed on individualization of each combined approach relative to the aforementioned factors. PMID- 2094475 TI - Maxillary deformation in unilateral coronal synostosis. AB - Distinct osseous structural differences exist between patients with unilateral coronal synostosis and those with "deformational plagiocephaly." Patients with unilateral coronal synostosis exhibit significant anterior displacement of the infraorbital rim relative to the ipsilateral frontal bone and contralateral infraorbital rim (p less than 0.005). Patients with deformational plagiocephaly are noted to have retrusion of the frontal bone and infraorbital rim on the involved side. The observed differences, documented utilizing computerized tomography, are easily appreciated on clinical examination, facilitating rapid distinction between these two entities. PMID- 2094476 TI - Major craniomaxillofacial reconstruction aided by microsurgical tissue transfer. AB - The application of microsurgical tissue transplantation in craniomaxillofacial deformities is presented by regional anatomic examples and discussion. PMID- 2094477 TI - Involvement of the thymus and cellular immune system in craniofacial malformation syndromes. AB - Craniofacial structures, the aortic arch, thymus, and parathyroid glands all arise from the embryologic pharyngeal pouches, and DiGeorge and Job craniofacial malformation syndromes have defined immunologic deficiencies. The question addressed by this study is whether patients with other pharyngeal pouch malformations could also have immunologic abnormalities. Twelve patients, 4 female and 8 male, were selected at random from the Tampa Bay Craniofacial Center. Their diagnoses included: cleft lip/cleft palate, hemifacial microsomia/Goldenhar syndrome, Treacher-Collins syndrome, craniofacial hemangiomata, cranio-synostosis syndromes, and Tessier 13 cleft. Fresh blood samples were analyzed against age-matched controls for immunoglobin number, using immunoelectrophoresis, T-cell, B-cell, and natural killer cell quantity via Coulter counter and monoclonal antibody labeling, as well as lymphocyte stimulation and response functions with phytohemagglutinin, concanavalin A, pokeweed mitogen, and Staphylococcus aureus mitogens. All patients studied had some abnormality of their immune systems. Seven had specific T-cell abnormalities and three patients had abnormalities in all three categories studied. This indicates that patients with any pharyngeal pouch malformation may have an abnormality of the immune system. PMID- 2094478 TI - Subcranial approach for the correction of hypertelorism. AB - The subcranial approach for the osteotomy of the skull base and orbital roof in cases with hypertelorism is described. Advancement of the fronto-orbital segments is performed, avoiding the transfrontal procedure, thus making frontal lobe retraction unnecessary. The advantages of this method are pointed out. PMID- 2094479 TI - Craniofacial deformation in cystic hygroma. AB - Mandibular and dentoalveolar deformities associated with cystic hygroma of the head and neck have previously been described. This small series has identified changes involving the entire craniofacial skeleton, attributable to both the local and distant effects of massive facial lymphangiomas, without evidence of any actual soft tissue ingrowth into bone. In view of the inability to excise such lesions and normalize the soft tissue anatomy, the surgical approach to the craniofacial skeletal abnormality should be to reserve the required osteotomies or ostectomies until the completion of facial growth. PMID- 2094480 TI - The treatment of sleep disorders of older people. AB - The National Institutes of Health Consensus Development Conference on the Treatment of Sleep Disorders of Older People brought together clinical specialists in pulmonology, psychiatry, psychology, geriatrics, internal medicine, other health care providers, and the public to address the cause, diagnosis, assessment, and specific treatments of sleep disorders of older people. Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighed the scientific evidence and prepared a consensus statement. Among their findings, the panel concluded that although sleep patterns change during the aging process most older people with sleep disturbances suffer from any of a variety of medical and psychosocial disorders. The panel recommended that the diagnostic evaluation of sleep disorders begin with a careful clinical evaluation performed by an informed primary care physician. When necessary, referrals should be made to individuals or centers with specialized skills and tools for therapy. The panel recognized two types of disorders for which treatment may be beneficial: obstructive sleep apnea and insomnia. The mainstay for treatment for sleep apnea is the use of nasal continuous positive airway pressure. A thorough medical evaluation is essential prior to initiating treatment for insomnia, as its causes may be of psychiatric, pharmacological, or medical origin. The panel recommended that hypnotic medications not be the mainstay of treatment for insomnia as they may have habit forming potential if overused. The full text of the consensus panel's statement follows. PMID- 2094481 TI - [Critical evaluation of the research on the etiology of violence towards children]. AB - This article is a critique of research concerning physical abuse and negligence towards children. Without systematically reviewing the literature on the subject, the author identifies the various determining factors of violence underlined by the three principal models--psychological, sociological and ecological--and profiles their contribution and limitations in building an etiology of violence. The author reveals that little research has been carried out based on an original gathering of data, that methodology lacks a certain rigour and that noticeable differences exist in the definition of variables. In light of this, the author suggests that identifiable risk factors be dealt with by using greater circumspection. The author also argues for the need of a systemic analysis of the determining factors of violence. PMID- 2094483 TI - [A space to construct desire...]. AB - It is a matter of being woman or simply of being? Is there actually a feminine way to be? Here, women put psychoanalysis into question. This article suggests a return to the notion of castration and to the developments surrounding the significance of the phallus. The castration experience is presented as being closely likely to the process of sexualization and to the individual's self realization. The authors advance the woman's point of view, which questions castration. They find that psychoanalysis does not provide an answer, but imposes a limit: that of a symbolic order in which the individual must fit. Within the limiting phenomenon of castration, there remains the need for every man and woman in contemporary Quebec society to share a sense of desire. PMID- 2094482 TI - [Loneliness among young people: collation of writings]. AB - Contrary to the popular belief that loneliness is typically associated with adults, and especially with older persons, this state can occur early in life. In fact, an increasing number of studies indicate that an important proportion of adolescents experience an intense episode of loneliness. This literature review describes loneliness among younger persons. We discuss the ampleness of the problem, the definition of the phenomenon, the feeling associated with loneliness, precipitating and predisposating factors and, finally, coping strategies to deal with this experience. PMID- 2094484 TI - [Clinical research methods in psychoanalysis. Report of the proceedings of the lecture "Reality and death in the therapeutic situation"]. PMID- 2094485 TI - [The analyst's pregnancy: fantasy or reality? Or does the reality surpass the fiction?]. AB - This article focuses on the pregnancy of analysts and its impact on the (reality) within analytical treatment. In this situation, the analyst on the one hand is caught between words and action, and on the other hand, begins to realize her pregnancy has an effect on patients, namely through emotional intensification of transference, almost instant awareness of the pregnancy by some, which incidentally sometimes leads to silence in the form of denial or inhibition. The analyst herself, in a transferential reaction, could seek to break the silence, along with the interrelation, while being torn between the "maternal preoccupations" directed toward her child as well as toward her patient. Beyond the study of attitudes or stereotyped themes, this article tries of identify the "transference dynamics" brought on by the issue of an analyst's pregnancy. In conclusion, the analyst's pregnancy, during the course of treatment, appears to distance itself from its event-related qualities and transforms itself into a mix of fantasy and reality, which can be analyzed like a dream or a deep-rooted souvenir. PMID- 2094486 TI - [Reality, death]. PMID- 2094487 TI - [To begin to believe. Working notes on a mother-daughter incest case and its implications on the formation of the pre-transitional object]. AB - Most psychoanalytic literature dealing with incest holds the premise that the act took place between a parent and a child of opposite sex. Incidentally, most of these cases involve a father-daughter incest (e.g. research by Julien Bigras). However, this is only one of four mathematically possible combinations. For instance, we tend to underestimate the occurrences and, consequently, the repercussions of mother-daughter incest relationships. The biological and psychological importance of the mother in the child's development radically influences the mother-daughter incest. In the reactualizing of transference, analysts, especially if they are female, often find themselves confronted with some of the most fundamental choices in the life of an infant, such as to live or to die, to grow or to cease to grow. It then becomes crucial to understand the most primitive components of the infant's early life. In such a case, an analyst must consult some of the most complex theoretical work covering the subject. The author, for her part, has greatly referred to the experiences of Renatta Gaddini, who insists on the importance of developing a pretransitional space during the analysis. This pretransitional space, however, is useless if the analyst is unable to follow it up by becoming a transformational object in the eyes of the patient, in the way described by Christopher Bollas: an object suggesting that the patient relive the steps leading from pre-thought to thought, from real to symbolic. Indeed, Bollas' research has allowed the author to develop a more accurate vision of what is at stake. At the same time, she was able to assess the amount of work still needed in that area of study, an area which, up to this day, offers only very little research to support the author's exploration. PMID- 2094488 TI - [Encounters with non-dreamers]. AB - When a patient's hardship is presented to a therapist as an unpleasant experience as much as a desired state, interest in the former's suffering tends to decrease. Furthermore, repetitive anecdotes and the refusal to collaborate isolate the therapist in a position of sadistic silence. During these moments when imagining and theorizing merge, therapists seek to protect themselves against doubt and irritability. The authors argue that they should avoid changing patients and basing strategies on a diagnostic. Instead, rather than struggle with the structure in which they work, therapists should confront the process during which their own feelings and interview tactics are at play. PMID- 2094489 TI - [Those who are loyal to death]. AB - As a contribution to the clinical treatment of melancoly, this article studies the transferential and counter-transferential dynamics of unmotivated female patients whose lethargy is due to a little or unrewarding mother-child relationship. After having identified their method of incorporating the maternal image, the author points out that the cult-type admiration bestowed on mothers provides a basis on which one can better understand the elements of this private religion focused on idolization rather than on idealization of the loved one. PMID- 2094490 TI - [Psychotherapy of loss and grief]. AB - For many years, survivors of the Holocaust in Israel and elsewhere have made little space in their lives for past memories. Indeed, they feared being overcome by them and influencing their children negatively as a result. When these people reach the age of putting their whole life into perspective, the mourning and loss processes are reactivated by the need to hold testimony. Also, they seek to be part of the continuity of crucial events that marked their past, particularly concerning the separation from their family of origin, network of friends and cultural community. Furthermore, since people belonging to the second generation grew up with this separation from family roots, they would develop fantasies often linked to a somewhat guilty complex. The authors present two clinical cases to illustrate each of the two themes in the article. PMID- 2094491 TI - [Madness and homelessness]. PMID- 2094492 TI - [Feminist intervention at Entre-Deux]. PMID- 2094493 TI - [The new certificate in mental health: foundation and interventional practices]. PMID- 2094494 TI - [Psychodynamic aspects of behavioral disorders in the senescent patient and their psychodynamic approach]. AB - Melanie Klein's therapy is comprised of elements likely to be transposed to senescence for a better understanding of certain disorders in pathological aging. To this day, several clinical states that appear for the first time at an advanced stage in life, such as certain forms of depression, deliria or intellectual deficiency, have not been satisfactorily explained psychodynamically. The author attempts to create a new approach with a Kleinien perspective. PMID- 2094495 TI - [Forgetting space in the plan of organization of services]. PMID- 2094496 TI - [The spider on the ceiling]. AB - This article is on the portrayal of insanity in Quebec literature and, in particular, on the relationships between Quebec literature and insanity. A look at Quebec history reveals how insanity follows the nature of society as it evolves from a religious base to a political one. Research shows that, from 1837 to 1920, insanity in literature was caused by an emotional shock, deception in love or thwarted ambitions. Between the first and second world wars, insanity was brought on by debauchery, money and women. So, for over a century, we see insanity as having punitive value. It's only in the 1950s that literature portrays insanity as a consciousness raiser: From having negative connotations, it suddenly has positive ones. Finally, from 1960 to today, insanity stems from failure, whether it be love-related, social or political. In most novels, the insane individual ends up dying. It's as if novelists had wanted to reinforce the notions of punishment, failure and despair linked to insanity. Why? PMID- 2094497 TI - [On the epidemiology of mental illnesses: update on recent data]. AB - The goal of this paper is to summarize recent epidemiological findings from community studies on mental illness prevalence and incidence among male and female respectively. The author refer mainly to the Epidemiological Catchment Area (ECA) research projects. A review of developments of the American Psychiatric Association classification of mental disorders is presented and implications of the new nosology on the epidemiologic method is offered. The data indicate that males and females vary significantly in prevalence and incidence of psychopathologies assessed in these studies. Results are compared to those collected for the Sante Quebec health survey. PMID- 2094499 TI - Access to health care. PMID- 2094498 TI - [The psychosocial profile of couples consulting a fertility clinic]. AB - The objective of this study is to draw the psychosocial profile of couples who consult fertility clinics. More specifically, it consists of a) comparing the psychosocial status of subjects who seek fertility consultation with that of normal subjects or individuals at grips with psychological problems; b) determining whether there are profile differences between men and women who seek fertility consultation; and c) assessing whether it is possible to predict the nature of the psychosocial profile of the subjects from various sociodemographic and medical characteristics. The sampling includes 30 couples who are consulting a specialist in a fertility clinic belonging to a Montreal-area hospital. Analysis of results shows that the psychosocial profile of subjects consulting a fertility clinic is midway between that or normal subjects and that of individuals suffering of psychological problems. The psychological status of men and women consulting a fertility clinic is different according to three variables: depression, self-esteem and stress. Finally, multiple regression analysis has allowed the author to identify several medical characteristics linked to the extent of the psychosocial difficulties experienced by the infertile subjects. PMID- 2094500 TI - Linking addressers of disease-specific needs. PMID- 2094501 TI - Lack of referral networks. A parent's perspective. PMID- 2094502 TI - The Spina Bifida Association of America: successes and shortcomings. PMID- 2094503 TI - The unique challenge of isolated populations. PMID- 2094504 TI - Provision of services at the Fort Peck Indian Reservation. PMID- 2094505 TI - Medical financial counseling program. PMID- 2094506 TI - Immigration and the provision of genetic services. PMID- 2094507 TI - Understanding the Southeast Asian health care consumer: bridges and barriers. PMID- 2094508 TI - Recent Mexican immigrant women in Los Angeles: implications for health care interventions. PMID- 2094509 TI - Genetic services, research, and insurance: tracing the legislative history. PMID- 2094510 TI - The authorization and appropriation process. PMID- 2094511 TI - A parent's perspective on creating change in legislation. PMID- 2094512 TI - The Federal Office of Maternal and Child Health's role. PMID- 2094513 TI - Genetic services: the March of Dimes' role. PMID- 2094514 TI - Voluntary agencies. PMID- 2094515 TI - Special considerations in genetic counseling with the deaf population. PMID- 2094516 TI - The New Jersey genetic service outreach project. PMID- 2094517 TI - How to seek funds from Federal and private sources. PMID- 2094518 TI - Funding available through the March of Dimes. PMID- 2094519 TI - Local funding: the Ohio experience. PMID- 2094520 TI - Educating legislators about genetic services. PMID- 2094521 TI - Designing public education brochures to reach low literate and minority persons. PMID- 2094522 TI - Public education through the media. PMID- 2094523 TI - Providing genetic services in Puerto Rico. PMID- 2094524 TI - A model genetic outreach program to meet the needs of geographically isolated populations. PMID- 2094525 TI - Genetic services for underserved populations. Consensus recommendations. PMID- 2094526 TI - Genetic services for underserved populations. Scope of the problem. PMID- 2094527 TI - Health care concerns of Hispanic populations. PMID- 2094528 TI - The effects of ethnocultural background on access to and use of genetic services. Unequal opportunity. PMID- 2094529 TI - Issues of definition in needs assessments. PMID- 2094530 TI - Measuring the impact of genetic disorders. PMID- 2094532 TI - Economic considerations in providing clinical genetic services. PMID- 2094531 TI - Needs assessment for genetic services in Texas. AB - In summary, we found that the availability of genetic services for the Medicaid patients with the 11 selected disorders follow the general population distribution for Texas. In general, there is no major geographic factor limiting availability of services. We also found that the calculation of Medicaid dollars paid according to the size of the metropolitan area in which the patient resides indicates that there are fewer Medicaid dollars spent on these 11 genetic disorders per person in the population in the larger metropolitan areas. We conclude that preliminary review of these data indicate that the urban poor may have a greater need for medical services that deal with genetic disease. PMID- 2094533 TI - Changes in access from birth to adulthood. A clinic model. PMID- 2094534 TI - An overview of barriers to care. PMID- 2094535 TI - A model perinatal genetics program. PMID- 2094536 TI - Immunoassays of secretory IgA and secretory component. AB - 1. A sandwich-type enzyme-linked immunosorbent assay (ELISA) is described for quantitation of secretory IgA (sIgA) in human serum, as well as an ELISA and a radioimmunoassay (RIA) for measurement of secretory component (SC) in human serum. Samples were reduced and alkylated prior to the measurement of SC. 2. Healthy individuals (N = 53) presented low levels of SC (median, 0.9 mg/l). The protein levels were significantly elevated when compared with the controls, in sera of women during the second (N = 31; median, 1.5 mg/l) and third (N = 35; median, 4.2 mg/l) trimesters of pregnancy and in sera of patients with alcoholic cirrhosis (N = 38; median, 2.4 mg/l) and acute viral hepatitis (N = 25; median, 2.4 mg/l). SC levels of women in the first trimester of pregnancy (N = 24; median, 0.5 mg/l) did not differ from the controls. 3. sIgA levels were also significantly elevated when sera of women in the third trimester of pregnancy (N = 41; median, 25.4 mg/l) and sera of patients with alcoholic cirrhosis (N = 32; median, 75.0 mg/l) or acute viral hepatitis (N = 38; median, 28.5 mg/l) were compared with controls (N = 49; median, 9.0 mg/l). Women in the first (N = 25; median, 7.7 mg/l) and second (N = 29; median, 10.2 mg/l) trimester of pregnancy did not present levels statistically different from the controls. 4. The results obtained for SC by RIA and ELISA were positively correlated (rs = 0.88; P less than 0.001). sIgA levels determined by ELISA were also positively correlated with the results of RIA-SC (rs = 0.77; P less than 0.001) or ELISA-SC (rs = 0.79; P less than 0.001). 5. The assays described are specific, relatively simple to perform, and can be useful for the study of the secretory immune system. PMID- 2094537 TI - Exposure to hydrocarbons and rapidly progressive glomerulonephritis. AB - 1. A case-control study of the relationship between the regular exposure to hydrocarbons and rapidly progressive glomerulonephritis (GN) was carried out in Sao Paulo, Brazil. Regular exposure was defined as 1 h or more weekly for 3 consecutive months or longer. We studied 17 patients with rapidly progressive renal failure and biopsy-proven crescentic GN and 34 matched hospital controls. 2. We found an increased risk of rapidly progressive GN associated with exposure to organic solvents (relative risk = 5.00; 95% confidence interval = 1.14 to 22.00). The frequency of exposure to solvents was 52.9% among the patients and 17.7% among the control subjects (P less than 0.05). However, no statistically significant increased risk was detected in those patients who had been exposed to fuels (relative risk = 3.25; 95% confidence interval = 0.76 to 13.89); the proportion of exposure to fuels was 47.1% among the patients and 20.6% among the control subjects. 3. Renal histologic findings suggest that immune complex mediated injury as well as a direct glomerular toxic effect may participate in the pathogenesis of rapidly progressive GN associated with hydrocarbon exposure. PMID- 2094538 TI - Radioimmunoassay of carboxyl and amino terminal fragments of parathyroid hormone for the evaluation of secondary hyperparathyroidism in chronic renal failure. AB - 1. Some parameters of calcium and phosphorus metabolism and the radioimmunoassay of plasma concentrations of both the carboxyl (COOH) (residues 53-84) and amino (NH2) terminal (residues 1-34) fragments of parathyroid hormone (PTH) were measured to evaluate secondary hyperparathyroidism in 68 patients with chronic renal failure (CRF), 34 of whom were on hemodialysis therapy. 2. The upper limits of the normal values for serum PTH-NH2 and PTH-COOH concentrations were 28 and 146 pmol/l, respectively. Patients with mild CRF (plasma creatinine (CRp) 1.2-2 mg/dl) had normal mean serum total calcium, low mean serum phosphorus, undetectable plasma levels of PTH-NH2 (less than 10 pmol/l), slightly elevated mean plasma PTH-COOH concentration and normal fractional excretion of phosphorus (FEP). Patients with moderate CRF (CRp 2.1-4 mg/dl) had normal mean serum concentrations of both total calcium and phosphorus, and elevated mean levels of both plasma PTH-COOH and PTH-NH2 associated with increased FEP. Patients with end stage CRF (CRp greater than 4 mg/dl) and those on hemodialysis had elevated mean serum phosphorus levels and decreased mean serum total calcium concentrations compared with those with mild and moderate CRF, and more pronounced increases in both mean plasma PTH-COOH and PTH-NH2. 3. The logarithm of plasma PTH-NH2, but not PTH-COOH, concentration correlated positively with FEP and serum phosphorus concentration and negatively with total serum calcium concentration, while the logarithms of both PTH-NH2 and PTH-COOH levels correlated positively with CRp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094539 TI - Facial expressions of neonate infants in response to gustatory stimuli. AB - Ten male and five female neonates (median age, 43 h) were tested with sweet, sour, and bitter stimuli. Facial expressions were videotaped for at least 60 s and analyzed in order to 1) assess early discriminatory function, and 2) determine constancies in the components of facial expressions elicited by different gustatory stimuli in order to evaluate the possibility of obtaining characteristic patterns of facial movements for each stimulus. Specific sets of facial movements were observed for each taste modality, demonstrating that newborn infants respond characteristically to these stimuli and implying the functionality of the gustatory system hours after birth. PMID- 2094540 TI - HPLC determination of norepinephrine, 5-hydroxytyramine and 5-hydroxytryptamine in rat brain using sodium dodecyl sulphate as ion-pair. AB - 1. A simple HPLC method using sodium dodecyl sulfate (SDS) and electrochemical detection for the determination of norepinephrine (NE), 5-hydroxytyramine (DA) and 5-hydroxytryptamine (5-HT) in brain regions is described. 2. The tissue extraction procedure involved only two steps: protein precipitation with perchloric acid and pH adjustment to near 3.0. When used in combination with methanol as ion-pair in the mobile phase, sodium dodecyl sulfate effectively separated NE (6.6 min), epinephrine (EPI, 7.9 min), DA (14.3 min) and 5-HT (29.0 min) and the high methanol concentration used prevented the overlapping of the metabolites and monoamines in their chromatographic peaks. 3. The method was sensitive (40 to 70 pg of monoamine can be quantified) and reproducible and the values obtained for cortex, hippocampus, striatum and substantia nigra were consonant with most literature data. PMID- 2094541 TI - Monoclonal antibody-based immunoenzymometric assay for serum human growth hormone. AB - A monoclonal antibody-based immunoenzymometric assay (IEMA) for the measurement of human serum growth hormone is described. Two high-affinity and complementary monoclonal antibodies were selected from a panel of 9 obtained upon fusion of SP2/O myeloma cells with spleen cells from a Balb/c mouse immunized against human growth hormone of pituitary origin. One monoclonal antibody was immobilized by attaching it to the walls of microtiter wells and the second was biotinylated. The reaction was quantitated by the addition of streptavidin-peroxidase. The sensitivity of the assay was 0.2 mIU/l and the intra- and interassay coefficients of variation for 4.6 to 46 mIU/l were less than 8.3 and 17.3%, respectively. Cross-reaction with human placental lactogen, human prolactin and rat growth hormone was less than 0.1% (w/w). Comparison of results obtained for 180 routine serum assays by radioimmunoassay and the assay described here had a correlation coefficient of 0.94 with a mean value of 16.3 +/- 1.3 (mean +/- SEM) and 13.3 +/- 1.2 mIU/l, with the IEMA providing values 18% lower than the RIA. The discrepancy emphasizes the necessity of redefining normal ranges before immunometric assays, like the one described, can be used routinely. PMID- 2094542 TI - Antinociceptive effects of calcium channel blockers in the rat. AB - 1. The effects of cinnarizine and nifedipine on the nociceptive threshold and opiate antinociception were evaluated by the rat tail-flick test. 2. Male Wistar rats (390-410 g) treated with intraperitoneal (ip) or intrathecal (it) cinnarizine, but not with it nifedipine, displayed a dose-dependent antinociception. The estimated AD50 values of cinnarizine were 3.55 micrograms/kg (confidence limits, 1.99 to 6.32) and 125.9 micrograms/kg (46.1 to 343.7) for the it and ip routes of administration, respectively. The effect of it cinnarizine was reduced by subsequent it administration of calcium chloride (0.1 mumol). 3. The it morphine-induced antinociception was potentiated by the previous it administration of cinnarizine (1.0 microgram/rat). The estimated AD50 of morphine was reduced from 10.4 (6.8 to 16.1) to 4.9 micrograms (3.6 to 6.5) by this dose of cinnarizine. The calculated potency ratio for these values was 2.14 (1.28 to 3.57). A similar potentiation was obtained with it nifedipine, but only when the drug was injected in combination with morphine. 4. It is concluded that the antinociception evoked by a systemically injected calcium channel blocker is dependent on passage of the drug across the blood brain barrier to act, at least in part, at a spinal site of action. 5. The mechanism of the antinociception induced by it injected calcium channel blockers appears to depend on the interaction of the drugs with Ca2+ binding sites in the spinal cord and, probably, on the type of voltage-sensitive calcium channel involved. PMID- 2094543 TI - Availability of calcium for noradrenergic contraction of the mouse isolated vas deferens is not altered during tolerance to and dependence on morphine. AB - 1. The present study assesses the influence of tolerance to and dependence on morphine on the availability of Ca2+ for contraction of the mouse isolated vas deferens induced by noradrenaline (NA). 2. Reducing Ca2+ content in the bathing solution from 2.5 to 1.2 or 0.6 mM significantly reduced the magnitude of NA induced contractions. This effect was similar in preparations obtained from control and tolerant/dependent mice (P greater than 0.05 at any Ca2+ concentration). 3. Omission of Ca2+ from the bathing solution caused a rapid and similar loss of responsiveness to a maximally effective concentration of NA (300 microM) in both groups (t1/2 less than 3 min, P greater than 0.05). 4. Vasa deferentia obtained from control and tolerant/dependent mice were equally susceptible to non-competitive antagonism of NA-induced contraction by verapamil (3 to 30 microM; pD2' values of 5.50 and 5.26, respectively, (P greater than 0.05 at any concentration of verapamil). 5. Preparations from tolerant/dependent mice displayed significant supersensitivity to NA, the magnitude of which was not influenced by modifying the Ca2+ concentration in the bathing medium (2.6- and 1.7-fold in 0.6 and 2.5 mM Ca2+, respectively, P less than 0.05). 6. I conclude that tolerance to and dependence on morphine are not associated with changes in the availability of Ca2+ for NA-induced contractions of the mouse vas deferens. PMID- 2094544 TI - Myocardial protection by verapamil and reperfusion following coronary occlusion. AB - 1. The hypothesis that early verapamil (VP) treatment in acute myocardial ischemia can enhance the effects of subsequent reperfusion was tested in open chest dogs submitted to 3 h of left anterior descending artery occlusion and 2 h of reperfusion. 2. Arterial pressure and heart rate were monitored continuously. The area at risk (AR) was determined by left atrial injection of 99technetium labeled microspheres soon after occlusion. The area of necrosis (AN) was identified histologically with triphenyl tetrazolium chloride and calculated as percent of AR. Myocardial preservation is reported as percent of AR spared from necrosis (AR-AN) x 100/AR. 3. Fourteen dogs received 0.2 mg VP, iv, 15 min after occlusion and 9 untreated dogs served as controls. Verapamil significantly reduced heart rate but did not affect blood pressure or the pressure-heart rate product. 4. Myocardial preservation was significantly greater in verapamil treated dogs than in control animals (51 +/- 20 vs 31 +/- 19%, mean +/- SD). However, area at risk (%) in the left ventricle was not significantly different in treated and control animals (31 +/- 12 vs 32 +/- 4%). 5. These data indicate that verapamil protects the ischemic myocardium in this occlusion/reperfusion model and that the mechanism of protection is probably related to a non hemodynamic, metabolic activity of verapamil. PMID- 2094545 TI - Influence of co-dergocrine on platelet aggregation. AB - In the present investigation, we studied the influence of co-dergocrine mesylate (dihydroergotoxin mesylate) on platelet aggregation induced by adrenaline, adenosine diphosphate (ADP) and collagen in vitro. Platelet-rich plasma was incubated with increasing concentrations of co-dergocrine (1.5, 3.0, 6.0, 12.0, 24.0, and 48.0 micrograms/ml). The lowest concentration of co-dergocrine tested (1.5 micrograms/ml) inhibited adrenaline-induced aggregation by 97%. Higher concentrations of the compound caused similar degrees of inhibition. ADP-induced aggregation was only decreased significantly (20%, P less than 0.001) by the highest concentration of co-dergocrine, whereas collagen-induced aggregation was not affected. Our results demonstrate that co-dergocrine selectively inhibits platelet aggregation triggered by adrenaline in vitro. PMID- 2094546 TI - Decremental propagation of reflex spikes along giant axons of the earthworm Amynthas hawayanus. AB - The constant-velocity conduction of an action potential evoked by stimulating the isolated nerve cord of the earthworm Amynthas hawayanus differs from the propagation of a reflex spike evoked by stimulating the epithelium of an epithelio-muscular-nerve-cord (EMNC) preparation and recorded between pairs of microelectrodes spaced every 10 segments along either giant axon. The reflex spike is decremental and lasts for no more than 20 segments before it eventually disappears. Secondary and tertiary spikes sometimes arise even before the disappearance of the primary spike, and disappear after propagating for a short distance. This decremental propagation is tentatively attributed to the summation of excitatory postsynaptic potentials from the synaptic impingings of afferent interneurons in a polysynaptic reflex arc. PMID- 2094547 TI - Blood glucose changes in the blue crab Callinectes sapidus Rathbun on transfer from sea water to air. AB - Intertidal decapods regulate their blood glucose with a significant but transitory (60 min) increase upon exposure to atmospheric air, and this has been considered to be an adaptative response related to the almost complete lack of the Pasteur effect in facultative anaerobes. In these animals we would not observe an increase in substrate availability to cope with the small amount of energy furnished by anaerobic pathways but rather a general metabolic depression. However, this hypothesis has never been tested by conducting similar experiments with infralittoral species. For this reason, groups of five Callinectes sapidus were transferred from sea water to atmospheric air and their blood glucose levels were determined 15, 30, 60, 120 and 240 minutes afterwards. Glucose levels increased gradually from 16.41 +/- 4.45 mg/100 ml to 127.18 +/- 33.40 mg/100ml (mean +/- SEM). The linear relationship between time of exposure and glucose levels suggests that intertidal and infralittoral species present different mechanisms of blood glucose regulation. PMID- 2094548 TI - Intrinsic heart rate after infusion of angiotensin II in rats with sino-aortic deafferentation. AB - We investigated the effect of the infusion of angiotensin II on intrinsic heart rate in rats with sino-aortic deafferentation. Sino-aortic deafferentated (SAD) rats studied 48 h after surgery presented significant tachycardia when compared with sham-operated rats (426 +/- 16 vs 338 +/- 6 bpm), but no change in intrinsic heart rate (369 +/- 9 vs 369 +/- 11 bpm). Infusion of angiotensin II into the SAD group 48 h after deafferentation did not produce an additional increase in heart rate (423 +/- 16 vs 426 +/- 16 bpm) or a change in intrinsic heart rate (369 +/- 11 vs 369 +/- 9 bpm) when compared with sham-operated rats submitted to saline infusion. Intravenous (iv) infusion of angiotensin II into sham-operated rats produced a significant increase in both heart rate (381 +/- 12 vs 338 +/- 6 bpm) and intrinsic heart rate (427 +/- 9 vs 369 +/- 11 bpm). These data indicate that a) tachycardia after SAD is not associated with an increase in intrinsic heart rate, b) in sham-operated rats, the tachycardia occurring after angiotensin II infusion is associated with an increase in intrinsic heart rate, and c) angiotensin II infusion does not alter the intrinsic heart rate of rats tested 48 h after sino-aortic deafferentation. We conclude that the increase in intrinsic heart rate caused by angiotensin II in conscious rats depends on the integrity of the baroreceptor reflex. PMID- 2094549 TI - Inhibition of gastric acid secretion by cholinergic stimulation of the lateral hypothalamic area. AB - Cholinergic stimulation of the lateral hypothalamic area with carbachol (1 microgram in 1 microliter) markedly inhibited gastric acid secretion in the anesthetized rat. Inhibition was blocked by prior micro-injection of atropine (4 micrograms/microliters) into the same brain area and was accompanied by an increased sodium content in the stomach. Muscarinic receptor mediated cholinergic inhibitory influence of the hypothalamus on gastric acid secretion is suggested by these results. PMID- 2094550 TI - [The proposal of the Interministerial Council concerning the inventory of food additives subject to a simplified testing method for requests for changes in the conditions of use]. PMID- 2094551 TI - [Eulogy on Jean-Emile Courtois (1907-1989)]. PMID- 2094552 TI - [Methods of hospital management of patients with HIV infection]. AB - Analysis of data on case-management and referral of persons infected by HIV is based upon a cross-sectional study at the national level. The evolution of trends over the last 2 years reveals a rise in the number of AIDS cases undergoing full hospital treatment and a decline in the number of seropositives hospitalised. Irrespective of the clinical presentation, there has been above an increase in hospital care day treatment and consultations. Amongst all AIDS patients there is a growing need for increased treatment and case in the home as well as intermediary length hospital case management--a crucial consideration for the future. PMID- 2094553 TI - [Partnership networks and social organizations]. AB - Psychological, ethical and political issues of the HIV and AIDS epidemic on one part, the pauperization of people with AIDS on the other have given birth to AIDS organizations and to a creative solidarity amongst PWA. Doctors and nurses in spite of a real professional stress show many proofs of readiness to give more of themselves in innovative new team-cooperation. In France, they are now organizing themselves into volunteer networks involving hospital and city doctors. Describing the two targets of the AIDS virus: the T4 cells and communication, the author shows how communication with the self and with others is blurred by this disease; recent statistics illustrate the economical, professional and social fragility faced by patient in terms of medicare, insurance, employment, housing and home care. The various functions ensure by volunteers and patients on one hand and by health professionals on the other in these new social networks are direct responses to these two psychological and economical main issues. After a recent trend towards dissociation of assistance and therapy, the two historical functions of hospital, are we about to see them reassembled again in new locations? PMID- 2094554 TI - [Diverse strategies to attempt to prevent the spread of HIV infections]. AB - AIDS, because of the seriousness of its diagnosis, as well as the fact that it is linked with such life-giving symbols such as blood and sperm, has often been presented as the plague of the 1900's. As is often the case with serious, misunderstood societal calamities, AIDS carries with its attitudes of guilt and denial; attitudes which have greatly hampered the beginnings of preventive actions. Due in particular to the pioneering actions of non-profit AIDS associations, France currently has a global policy which encompasses prevention, information, and solidarity. The development and installation of this policy has brought to light practical problems which are ethically and morally important as well. Although the general public's understanding of the means of contamination is increasing, there remain a certain number of false conceptions which are difficult to overcome in information-based, mass media campaigns. As far as behavior-oriented prevention programs are concerned, condom promotion must often be carried out within certain limits of expression, particularly those of certain religious influences. Solidarity and ethics campaigns raise often sensitive human rights topics such as homosexuality and work-related issues. AIDS has thus a much broader scope than a public health subject, it involves the reflection and consideration of collective human and societal values. PMID- 2094555 TI - [Socioeconomic aspects of human immunodeficiency virus (HIV) infection in developing countries]. AB - The assessment of the socio-economical aspects of the human immunodeficiency virus (HIV) infection is difficult because of the relative scarcity of information. This study addresses mainly the socio-economic aspects of the AIDS pandemic in the inter-tropical zone of Africa, which, at the moment, constitutes the epicenter of the disease. In the absence of a possible radical treatment, the HIV infection prevalence should range between 25 and 30 million individuals by the year 2000 in the world, and the number of cases of AIDS, between 5 and 6 million, among which 4 to 5 million in the developing world alone. At the current rate, the overmortality rate related to AIDS in Africa is estimated at 0.1%, which should result in a drop by 30% of the Gross National Products advance (GNP). Each case of AIDS in Africa leads to a loss of productivity of 8.8 years. Already, losses caused by AIDS screening and its medical treatment in five countries of Central Africa should exceed the total amount of the foreign assistance received by each country. The estimated economic weight of the AIDS attendance is 15 to 20 times more heavy for a developing country than for an industralized one. Overcoming economically the cost of AIDS is an objective impossible to reach for deprived countries. PMID- 2094556 TI - [Socioeconomic aspects of HIV infection. Summary and conclusions]. PMID- 2094557 TI - [Eulogy on Louis Justin-Besancon (1901-1989)]. PMID- 2094558 TI - [The teaching of surgical specialties in France to foreign students: apropos of an inter-university specialty diploma in orthopedic surgery and traumatology]. AB - Foreign doctors who wish to be specialised in a particular branch mainly register themselves for a D.I.S. (Specialised Inter-university Diploma). The curriculum to this diploma is described through its Orthopaedics and Traumatologic Surgery branch and its drawbacks are analysed, namely lack of strict selection at entrance, insufficient theoretical courses and specially lack of practical training. More over, figures concerning the first batch show a large number of students registered in the first year while only a few succeeded the final examination. The consequences of such a poor formation might be serious. Solutions are proposed after comparison with the organisations retained in other countries. Any reform should firstly describe the aims of this postgraduate educational programme to foreign students. PMID- 2094559 TI - [The physical fitness visit: a serious medical procedure for the surveillance of sportsmen]. AB - Assessment of physical capability is especially important in sports medicine. It allows the choice of the appropriate sport, and the biomedical follow-up of the health of the sportsman engaged in a monitored training. The so called aptitude examination is a responsible action which requires time, an accurate clinical sense and involves the responsibility both of the general practitioner and of the sport medicine specialist. During the medical follow up, with the help of specialized functional tests, the physician may detect a state of overtraining and start a dissuasive action against doping habits. PMID- 2094560 TI - [The dynamic study of the human body using MRI]. AB - This work deals with dynamic anatomy of human body explored by magnetic resonance imaging (MRI). Recent development of MRI pulse sequences allow very fast data acquisition. Using an 1,5 Tesla system (General Electric--CGR, Signa), different body segments have been explored, in two different ways. The first approach consisted in a cinematographic display of anatomical sections of an articulation obtained in different positions. The result shows the movement of the articulation. The second approach consisted in the examination of a single slice several times, with cardiac synchronization ("gating"). the result is the evaluation of phase desynchronization, measuring the flow directions and the velocity of circulating fluids. The results are shown as a video tape with commentary. It starts with the joints: the ankle, the knee, the wrist, the hand, the cervical spine, de cervico-occipital junction, the temporo protrusion during deglutition and the ocular movements (normal and pathological), according to different planes, are successively proposed. Finally, flow kinetics are shown: cardiac movements and supra-aortic arterial flow, the intracranial cerebro-spinal fluid circulation, in normal and pathologic (intra-cranial hypertension) cases. The exposition is concluded by showing a work in progress on urine flow during micturition. PMID- 2094561 TI - [Anatomy today]. PMID- 2094562 TI - [The contribution of experimental embryology to medicine and surgery]. PMID- 2094563 TI - [The biology of prions, a response to the enigma of spongiform encephalopathies of sheep and humans]. AB - Prions are small proteinaceous infectious particles without nucleic acids. The prion protein arise from a cellular protein by a post-transduction event and constitute amyloid deposits. Prions are the agent of animal and human spongiform encephalopathies which evolve on simultaneous infectious and genetic dependence in the absence of a detectable immune response. PMID- 2094564 TI - [Then hemodynamic efficacy of transcutaneous cardiac stimulation]. AB - Bradyarrhythmia or asystole is the most common rhythm disturbance with ventricular fibrillation and tachycardia, for 30-40% of patients admitted in intensive coronary care units. Already use in the therapy of bradyarrhythmia or asystole, as a method of emergency, immediately in place, the external pacing is very useful in an out of hospital therapy with personnel skilled in its use until the initiation of support therapy in coronary care units. Actually, with less significant side effects (no severe pain, no strong muscular contractions, no skin burns) and a best innocuity and tolerance based on the employment of larger adhesive pre-gelled patches, temporary transcutaneous cardiac stimulation is not only confined to unconscious patients but also in case of severe bradycardia, complete AV block in conscious patients. Our hemodynamic study shows a good level of systemic pressure and of cardiac index to permit the transport of patients in coronary care units in good conditions. Furthermore, the experimental study demonstrates the importance of the polarity of the electrodes and of the duration of the stimulus (more than 10 ms) to minimize the threshold (mA/cm2) so as to increase the tolerance in clinical application. Transcutaneous cardiac pacing is a simple and rapid pacing procedure with effective hemodynamic results for victims of out-of-hospital cardiac arrest and can be easily used in conscious patients without any complication. PMID- 2094565 TI - [Problems common to anesthesia journals]. PMID- 2094566 TI - [The effects of isoflurane on bleeding in otorhinologic microsurgery]. PMID- 2094567 TI - [Indomethacin in severe cerebral contusions with intracranial hypertension]. AB - In five head-injured patients with cerebral contusion and oedema in whom it was not possible to control ICP by hyperventilation and barbiturate sedation, indomethacin Confortid was used as a cerebral vasoconstrictor drug. In all patients indomethacin reduced ICP below 20 mmHg for several hours. Studies of cerebral circulation and metabolism during indomethacin treatment showed a decrease in cerebral blood flow (CBF) at 2 hours. After 7 hours. ICP remained below 20 mmHg in three patients, and these still had reduced CBF. In two patients a return of ICP and CBF to pretreatment levels was observed. In all patients indomethacin treatment was followed by a fall in rectal temperature. Outcome scaling has not yet been performed, but all patients left hospital without neurological deficits. These results suggest that indomethacin is an alternative in the treatment of intracranial hypertension in head-injured patients. PMID- 2094568 TI - [The use of the Haemolite Cell Saver in cardiovascular surgery]. AB - In eighteen adult patients scheduled for cardiac and vascular surgery, shed blood was treated with the Haemonetics Cell Saver Haemolite. On average by patient, the autologous blood volume restored was 471.94 +/- 235.7 ml. The haemoglobin level was 16.88 g.dl-1 and haematocrit level was 49.31 +/- 7.2%. Thirteen by eighteen patients did not require any homologous blood transfusion. The Cell Saver Haemolite technique is restricted to moderate and gradual peroperative bleeding. This technique is particularly designed for vascular and pediatric surgery. Postoperative shed blood salvage is a marginal indication. PMID- 2094569 TI - [The value of peripheral blocks in pediatric anesthesia]. PMID- 2094570 TI - [Peripheral neurologic complications of brachial plexus blocks]. AB - Nerve injury can arise as a complication of peripheral nerve block anesthesia. From the review of the literature remain three factors which alone or in combination, are of special etiologic interest: nerve lesion due to the needle or intraneural injection; toxic effects of the agent injected overall when epinephrine is used; ischemic trauma. The symptoms of such nerve lesions vary from light paresthesia to painful dysesthesia and motor weakness or paralysis. The clinical analysis of these complications does not differ from that in other neurological patients, but must be realized effectively and immediately for avoiding a lawsuit. These postanesthetic neuropathies may benefit from specific treatment or even surgical exploration and external neurolysis. The block should be handled with care: rough paresthesia seeking and intraneural injections should be avoided; short bevel needles and plane solutions should be preferred. PMID- 2094571 TI - [3 peroperative anaphylactic accidents due to latex or ethylene oxide]. PMID- 2094572 TI - [Immediate hypersensitivity to latex. Apropos of a peroperative anaphylactic shock]. PMID- 2094573 TI - [2 pioneers of university anesthesiology]. PMID- 2094574 TI - [Posology of propofol in relation to age in pediatric ORL anesthesia]. PMID- 2094575 TI - Genetic restriction of protective immunity to Plasmodium yoelii sporozoites. AB - Ten congenic strains of mice were immunized with irradiated sporozoites of Plasmodium yoelii. When challenged with viable sporozoites, only two strains had a high proportion of animals which did not develop blood-stage infections. Genes both within and outside the H-2 region affected the degree of protection. Immunity did not correlate with anti-sporozoite antibody levels. In vivo depletion of CD8+ T cells did not alter immunity in two of three congenic strains, implying the existence of a novel mechanism of cell-mediated immunity. PMID- 2094576 TI - Evaluation of vaccines designed to induce protective cellular immunity against the Plasmodium yoelii circumsporozoite protein: vaccinia, pseudorabies, and Salmonella transformed with circumsporozoite gene. AB - In an attempt to induce a protective cytotoxic T-cell mediated immunity against sporozoites of Plasmodium yoelii, the gene encoding the P. yoelii circumsporozoite (CS) protein was engineered into three live vectors: vaccinia, attenuated pseudorabies, and attenuated Salmonella typhimurium. Balb/c mice were immunized with 1-4 doses of 10(8) pfu of the vaccinia construct (IP), 3 doses of 10(5), 10(6) or 10(7) pfu of pseudorabies construct (IV), and 3 doses of 10(9) salmonella transformants (orally). In the case of vaccinia and pseudorabies constructs, an excellent immune response was obtained as measured by antibodies to sporozoites. No protection or delay in prepatent period was seen in any of the experimental animals when challenged with 200 (vaccinia, pseudorabies) or 100 (salmonella) sporozoites, although mice immunized with irradiation-attenuated sporozoites were consistently protected against challenge with greater than 10(4) sporozoites. Since other vaccinia, pseudorabies, and salmonella CS constructs have been shown to induce cytotoxic T lymphocytes (CTL) against the CS protein, it is likely that CTL against the CS protein were induced during these studies. It is currently unclear if the vaccines did not induce the appropriate CTL or inadequate numbers of CTL, or if CTL against the P. yoelii CS protein are inadequate to protect against sporozoite challenge. PMID- 2094577 TI - The development and routine application of high-density exoerythrocytic-stage cultures of Plasmodium berghei. AB - Methods are reviewed for the culture of the exoerythrocytic stages of Plasmodium berghei wherein development reproducibly reflects growth observed in vivo in laboratory rodents. The combination of these methods with the culture of both asexual and sexual blood stages has allowed the completion of the entire vertebrate phase of malaria development in vitro. The development of new methods for high-density exoerythrocytic-stage culture combined with robust statistical analysis of parasite growth by morphological (light microscopy), or DNA probe methods now allows the critical and precise evaluation of chemotherapeutic or immunological treatments. These methods are illustrated by data obtained on pyrimethamine, primaquine and a hydroxynaphthoquinone. Some of the new avenues of research made feasible by the high-density cultures, e.g., direct immunization to produce monoclonal antibodies and biochemical studies are discussed. PMID- 2094578 TI - Human immunization with attenuated sporozoites. AB - Studies conducted between 1971 and 1975 showed that attenuated sporozoites can induce protection against human malaria. Three volunteers were protected against challenge with either a homologous or heterologous strain of Plasmodium falciparum after being exposed to a total of 440-987 X-irradiated mosquitos on 6 8 occasions over a period of 10-38 weeks. Protection lasted for at least 8 weeks, but not 16 weeks, after the last immunization with irradiated sporozoites. Another 7 volunteers were not protected against challenge with a homologous strain after exposure to a total of fewer than 200 irradiated mosquitos, infected with either P. falciparum or P. vivax, on 2-4 occasions over a period of 4-17 weeks. These studies provide an encouraging basis for pursuing the development of a sporozoite vaccine against human malaria. PMID- 2094579 TI - Delayed-type hypersensitivity and protection in mice following immunization with Plasmodium berghei sporozoites. AB - The measurement of footpad swelling (FPS) following the inoculation of sporozoite antigen (Ag) into the hind footpad (HFP) of outbred mice was used as an in vivo test of delayed-type hypersensitivity (DTH) to attenuated sporozoite immunization. An attempt was made to correlate DTH with protective antisporozoite immunity. The optimum time for testing DTH following a single intravenous immunization was four days. The optimum sensitizing dose was 1 x 10(5) attenuated sporozoites. A single immunization gave a greater FPS than multiple immunizations. Mice immunized with irradiation-attenuated sporozoites could be protected from a lethal challenge with nonattenuated sporozoites. The FPS response to mosquito debris Ag was minimal in mice sensitized by bites from infected mosquitos. Nude mice failed to develop an FPS response and could not mount a protective immunity with attenuated sporozoites. However, splenectomized mice did have an FPS response following sensitization. Mice infected with blood stage parasites had negligible FPS response to sporozoite Ag. The FPS response to sporozoite Ag proved to be a correlate of DTH in mice sensitized with sporozoites. PMID- 2094580 TI - A malaria sporozoite surface antigen distinct from the circumsporozoite protein. AB - Monoclonal antibody NYS4 recognizes a single 140 kDa antigen on the surface of Plasmodium yoelii sporozoites, an antigen which is distinct from the extensively characterized circumsporozoite (CS) protein. To more thoroughly characterize this additional surface component, a genomic expression library was screened with NYS4 and an immunoreactive clone (M4) was obtained which expressed part of the antigen gene. The deduced amino acid sequence of the M4 peptide included two unique repetitive sequences of amino acids and a conserved sequence motif which is found in several proteins including the CS protein (region II). The cloned DNA hybridized to a PCR (polymerase chain reaction) amplified sporozoite mRNA demonstrating the sporozoite-stage expression of this gene. A synthetic peptide of one of the repeats, (Asn-Pro-Asn-Glu-Pro-Ser), was recognized by NYS4 and mice immunized with (Asn-Pro-Asn-Glu-Pro-Ser)3 conjugated to KLH (keyhole limpet haemocyanin) produced high levels of antibodies that reacted with the surface of sporozoites and specifically to the 140 kDa antigen. Thus, at least two different proteins are on the surface of the P. yoelii sporozoite indicating that the immunoreactive exterior of the infective stage of malaria parasites is more antigenically complex than previously thought. PMID- 2094581 TI - Localization of CS and non-CS antigens in the sporogonic stages of Plasmodium yoelii. AB - Monoclonal antibodies (MAbs) and colloidal gold probes were used to localize circumsporozoite (CS) protein and two unrelated polypeptides in developing oocysts and salivary gland sporozoites of the 17X (NL) strain of Plasmodium yoelii. MAbs NYS1, NYS2, and NYS3 recognized different epitopes of the P. yoelii CS protein and produced similar patterns of immunolabelling on developing oocysts and sporozoites. A small percentage of oocysts contained developing sporoblasts and sporozoites that did not exhibit surface reactivity to MAbs NYS1, NYS2 or NYS3, although internal labelling was associated with endoplasmic reticulum (ER). These sporozoites were still capable of completing development and invading salivary glands where they could be found adjacent to sporozoites with densely labelled surface coats. If these sporozoites are infective, their presence may explain in part the failure of CS vaccines to completely protect immunized animals against challenge. The non-CS antigen recognized by MAbs NYS4 did not become abundant until late in sporogony. Some gold labelling was associated with the surface of budding and mature sporozoites, but the antigen was most abundant within the cytoplasm and micronemes. A second non-CS antigen identified by NYS5 first appeared in 7-day-old oocysts, although labelling was sparse. Small quantities of antigen appeared on the sporoblast membrane, cytoplasmic clefts and ER of oocysts and was associated with micronemes and the surface of budding and mature sporozoites. As the role played by non-CS antigens in the biology of the parasite is not yet known, further characterization of their function is needed before their potential as vaccine candidates can be determined. PMID- 2094583 TI - A liver-stage specific antigen of P. berghei identified by a monoclonal antibody. AB - Stage-specific immunity (to the sporozoite, the asexual blood-stages and the sexual stages of malaria) has been well documented and antigens from each stage are being tested for their potential as vaccine candidates. Recently it has become clear that the liver stage can also be the target of protective immune responses; however, only the circumsporozoite protein has been identified as a protective liver antigen. It is critical for vaccine evaluation and development to identify other liver antigens and assess their potential role in immunity. In this paper we describe a monoclonal antibody, which recognizes a liver-specific antigen of Plasmodium berghei (referred to as Pbl1). Passive immunization studies using this antibody suggest that it may influence the course of sporozoite induced infections. PMID- 2094582 TI - The conformational restriction of synthetic vaccines for malaria. AB - The effectiveness of synthetic vaccines is dependent upon the chance event that antibodies formed against largely disordered peptides can bind native protein surfaces which are often ordered. To improve on this situation, new methods are being developed for the conformational restriction of synthetic peptides. Cognate peptide sequences often form predictable secondary structures in proteins characterized by distinct hydrogen-bonding patterns. These weak hydrogen bonds have now been replaced with covalent mimics to conformationally restrict selected peptides to the Type 1 reverse turn and alpha helix. Potential uses for this chemistry are discussed in the context of malaria vaccines. The peptide component of a Plasmodium falciparum sporozoite vaccine, acetyl-(ASN-ALA-ASN-PRO)3-NH2 has been conformationally analysed using two-dimensional nuclear magnetic resonance spectroscopy. These studies are consistent with the formation of transiently ordered turnlike structures which provide a guide for the design and synthesis of a conformationally restricted synthetic vaccine. To assess the effects of conformational restriction and chemical modification on the sporozoite vaccine, ASN side-chains were linked around proline with ethylene bridges. Polyclonal antibodies to this shaped peptide show a strong cross-reaction with living sporozoites. PMID- 2094584 TI - Pre-erythrocytic stage malaria parasites: non-circumsporozoite protein antigens. AB - A series of non-circumsporozoite proteins found in pre-erythrocytic parasites are being developed as putative vaccine candidates. It is anticipated that these will be useful in addition to, rather than instead of, the CS (circumsporozoite) vaccines. It is likely that a greater understanding of the basic biology of malaria parasite-host relationships will lead to development of improved malarial vaccines. PMID- 2094585 TI - Presence of a circumsporozoite-like protein in micronemes of blood-stage merozoites of malaria parasites. AB - We demonstrate for the first time the presence of a circumsporozoite (CS)-like protein in invasive blood stages of malaria parasites. Immunogold electron microscopy using antisporozoite monoclonal antibodies localized these antigens in the micronemes of merozoites. Western immunoblot and two-dimensional gel electrophoresis of mature blood-stage extracts of Plasmodium falciparum, P. berghei, P. cynomolgi, and P. brasilianum identified polypeptides having the same apparent molecular mass and isoelectric points as the corresponding sporozoite (CS) proteins. The CS-like protein of merozoites is present in relatively minor amounts, compared to the CS protein of sporozoites. Mice with long-term P. berghei blood-induced infections develop antibodies which react with sporozoites. PMID- 2094586 TI - Immune responses to sporozoite antigens and their relationship to naturally acquired immunity to malaria. AB - This paper reviews some of the epidemiological approaches that have been explored and gives some examples of how these methods have been used to investigate naturally acquired immunity to sporozoite infections. PMID- 2094587 TI - Antibody responses to Plasmodium falciparum and P. vivax sporozoites in areas with stable and unstable malaria. AB - Availability of synthetic and recombinant peptides reproducing the repetitive regions of the circumsporozoite (CS) proteins of Plasmodium falciparum and P. vivax has allowed the development of assays for the detection of specific antibodies and of potential subunit vaccines. Knowledge of the immune responses to malaria sporozoites is a prerequisite for the optimal design of a sporozoite antigen-based vaccine. Studies carried out in areas with stable P. falciparum malaria (United Republic of Tanzania) have shown that antibodies against the synthetic peptide (NANP)40 increase as a function of age. Cluster analysis revealed marked inter-household variation of the anti-sporozoite antibody response, despite comparable risks of exposure to infectious bites. An age related prevalence of anti-P. vivax sporozoite antibodies has been observed in an area of Sri Lanka with unstable malaria, using a 45-mer synthetic peptide reproducing a defined sequential array of the two main 9-mer variants of the P. vivax CS protein. In this area, anti-(NANP)40 antibodies became detectable after the first epidemic of P. falciparum malaria. Interestingly, their prevalence also increased with age. Since this population had not been exposed to P. falciparum malaria for at least 10 years previously, one can suggest that anti-sporozoite antibodies reflect the relative exposure to infectious bites in the different age groups, and, in turn, the transmission of the disease. This can be particularly useful in areas where entomological indices of transmission tend to be unreliable because of the low vectorial capacity and wide fluctuations in vector densities. PMID- 2094588 TI - Human studies with synthetic peptide sporozoite vaccine (NANP)3-TT and immunization with irradiated sporozoites. AB - The synthetic peptide Plasmodium falciparum circumsporozoite (CS) protein conjugate vaccine (NANP)3-TT was safe when given parenterally to 202 volunteers. However, with a few notable exceptions, antibody responses were low and could not be boosted. Vaccinees' lymphocytes did not proliferate when exposed in vitro to (NANP)3. The tetanus toxoid (TT) carrier immunomodulated the response to the CS peptide in that both epitopic suppression and immune enhancement were demonstrated during the course of the clinical trials. During efficacy challenge studies, 1 of 7 vaccinees was protected against sporozoite challenge and in other vaccinees the prepatent period was significantly delayed. P. falciparum-infected mosquitos were irradiated with 20,000 rad (200 Gy). Five volunteers were immunized with 54, 55, 224, 663, and 715 total infective bites of irradiated mosquitos in an attempt to immunize with attenuated sporozoites. Four of these volunteers had significant humoral and cellular immune responses. Two volunteers (who received the largest immunizing doses) were challenged by the bites of infective mosquitos and both developed parasitaemia. In the volunteer with the highest antibody titre there was a marked delay in patency as determined by serial plasmodial cultures. T-cell clones are being obtained and characterized. PMID- 2094590 TI - Testing of Plasmodium vivax CS proteins in Saimiri monkeys. AB - Recombinant proteins directed against the circumsporozoite (CS) protein of Plasmodium vivax were tested for safety, immunogenicity, and efficacy in Saimiri sciureus boliviensis monkeys. The monkeys were immunized 3 times with either alum or muramyl tripeptide as adjuvant, and were challenged with 10,000 sporozoites (P. vivax, Salvador I strain) from mosquitos infected by membrane feeding on gametocytes from chimpanzees. Antibodies, measured by indirect immunofluorescent antibody tests and enzyme-linked immunosorbent assays, were induced by all the vaccines. Six of 42 monkeys immunized with recombinant or synthetically produced vaccines were protected. Two of 6 monkeys immunized with irradiated sporozoites were protected. Saimiri appear to be less susceptible than are humans to sporozoite infection. Therefore, the predictive usefulness of this model must await the results of comparable trials in monkeys and humans. PMID- 2094589 TI - Interferon-alpha and synthetic peptide malaria sporozoite vaccine in non-immune adults: antibody response after 40 weeks. AB - Adults with no known immunity to sporozoites received, i.m., at weeks 0 and 8 two single 200 micrograms doses of a peptide Plasmodium falciparum sporozoite vaccine conjugated to tetanus toxoid ((NANP)3-TT) plus placebo (group 1) or interferon alpha (IFN-alpha) (group 2) and were followed for antibody responses at weeks 4, 12 and 40. Peak antibody responses were observed at week 12. At week 40, a greater than or equal to 4-fold increase in antibody titre to sporozoites in IFA, or to (NANP)50 in ELISA was still detectable in 6 of 12 (50%) volunteers in group 1 and in 16 of 25 (64%) in group 2. Peak antibody titres in IFA and ELISA decreased with a rate of 0.8% and 0.5% per week, respectively. PMID- 2094591 TI - Anti-sporozoite antibodies. AB - Development of anti-sporozoite vaccines based on CS (circumsporozoite) proteins has preceded a thorough understanding of the basic biology of sporozoite-hepatic cell interactions. Investigation of these interactions can only serve to further refine the existing sporozoite vaccines, as well as provide a rationale for the design of other vaccine candidates. PMID- 2094592 TI - Evaluation of an in vitro assay aimed at measuring protective antibodies against sporozoites. AB - We have evaluated the in vitro biological activities of antibodies directed against sporozoites and compared them with their capacity to protect against challenge with both human and rodent malaria. The anti-Plasmodium falciparum antibodies evaluated with the test included monoclonal antibodies (MAbs) NFS1 and NFS2 as well as polyclonal antibodies contained in human hyperimmune sera directed against sporozoites of P. falciparum. The inhibitory effect of these antibodies was dependent on their concentration. However, total inhibition was not observed except occasionally with highly concentrated MAbs (10-100 micrograms/ml). Strong but also incomplete inhibition was observed with sera from humans living in hyperendemic areas. In the P. yoelii rodent system, we tested sera from mice immunized with subunit vaccines. None of these mice were protected in vivo against challenge with 40-200 sporozoites. In vitro only a sub-total inhibition was achieved (maximum 91% at 1:10 serum dilution). In contrast, we tested sera from mice that received NYS1, an IgG3 MAb, in passive transfer and were protected against challenge with 5000 sporozoites. At 1:10 dilution, 100% inhibition was achieved in vitro while IFA titres from these mice were similar to those of vaccinated mice. These data show a close correlation between in vivo and in vitro findings and thus suggest that the inhibition of liver-stage development assay (ILSDA) appears appropriate to evaluate the potential of antibodies. PMID- 2094593 TI - Use of non-human primate hepatocytes for in vitro study of the pre-erythrocytic stages of malaria parasites. AB - Methods were developed that allow invasion of sporozoites from simian malaria parasite species (Plasmodium cynomolgi, P. knowlesi, P. coatneyi, P. inui, P. gonderi, P. fragile) and development to schizont stages in rhesus and Saimiri monkey hepatocytes. The P. cynomolgi-rhesus monkey model was used to study inhibition of schizont development using monoclonal antibodies (MAbs) produced against the circumsporozoite (CS) protein of various strains and species of malaria parasites. Immunoelectron microscopy, using gold-labelled MAbs and cultured parasites, demonstrated that the CS protein persists in 7-day old liver stages of P. cynomolgi, but is not expressed at the surface of infected hepatocytes. A rhesus monkey was immunized with autologous hepatocytes (collected by biopsy) infected in vitro with liver stages of P. cynomolgi. This immunization elicited antibodies reacting with sporozoite, liver stage, and blood-stage parasites. In addition, human malaria parasites (P. falciparum, P. vivax, P. malariae) have been cultured in Saimiri or rhesus monkey hepatocytes. The P. vivax-Saimiri monkey model was used to study inhibition activity of sera from Saimiri monkeys experimentally immunized with recombinant P. vivax CS proteins. Post-immunization sera inhibited the parasite development, thus demonstrating the induction of antibodies effective against sporozoites. No relationship, however, was detected between in vitro inhibition and in vivo protection or antibody titres determined by ELISA or IFA. PMID- 2094595 TI - Cellular and humoral immune responses to a recombinant P. falciparum CS protein in sporozoite-immunized rodents and human volunteers. AB - The immune responses of sporozoite-immunized rodents and of human volunteers exposed to multiple bites of irradiated Plasmodium falciparum infected mosquitos have been investigated using a yeast-derived recombinant P. falciparum circumsporozoite (rPfCS) protein. The murine immune response to immunization with rPfCS was not genetically restricted. Nine different murine haplotypes, when immunized with rPfCS, developed high levels of antisporozoite antibodies detectable by IFA and RIA. In addition, injection of rPfCS induced a secondary antibody response in P. falciparum sporozoite-primed mice. Murine T-cell epitopes were mapped in the C terminus of the rPfCS protein using overlapping synthetic peptides. The human T-cell response was investigated using T-cell clones derived from peripheral blood lymphocytes (PBL) of a P. falciparum sporozoite-immunized volunteer. A total of 40 CD4+ T-cell clones were obtained. Stimulation indices ranged from 2.5 to 103.4 following challenge with rPfCS in the presence, but not in the absence, of antigen-presenting cells. The clones were specific for rPfCs and did not proliferate or secrete lymphokines when challenged with yeast-derived recombinant P. vivax or P. berghei CS protein or with a yeast-extract control. The clones also recognized the native CS protein in extracts of P. falciparum, but not P. berghei or P. cynomolgi, sporozoites. PMID- 2094594 TI - Plasmodium sporozoite-host cell interactions during sporozoite invasion. AB - In vitro and in vivo studies were performed to clarify the nature of some interactions between Plasmodium berghei sporozoites and rodent host cells. Videomicroscopic observations were made on in vitro interactions between sporozoites and cultured host cells (rodent peritoneal macrophages, W138 human lung fibroblasts, and HepG2 human hepatoma cells). The results showed a diversity of dynamic interactions and sporozoite activities, including active sporozoite penetration, often followed by sporozoite escape, killing of invaded macrophages, phagocytosis of sporozoites by macrophages, and elaboration of a weblike structure by the sporozoite, following its escape from cells. Other studies were performed to examine host cell inflammatory responses to challenge sporozoites in the livers of rats that had been previously immunized with radiation-attenuated sporozoites. The results showed a variety of focal inflammatory infiltrates in the livers of the challenged animals. The relevance of these observations to the problems of sporozoite invasion into native and immunized animals is discussed. PMID- 2094596 TI - Role of circumsporozoite protein-specific T-cells in protective immunity against Plasmodium berghei. AB - The Plasmodium berghei circumsporozoite (CS) protein-specific T-cell repertoire was analysed in C57Bl/6 (H-2b), Balb/c (H-2d), and C3H/HeN (H-2k) mice immunized with irradiated sporozoites and the proliferative responses were correlated with the protective status of each strain. Splenic lymphocytes responded to the priming antigen, but the responses varied according to both murine strain and immunization schedule. Analysis of cytolytic T lymphocyte (CTL) responses in mice immunized with irradiated P. berghei sporozoites or with a Salmonella-recombinant CS protein construct revealed that each immunization induces CTLs recognizing different epitopes on the target cells. The variations in immune reactivities among different murine strains to the CS protein antigens and the variations in the responses to the authentic versus recombinantly expressed CS protein suggest that distinct immune mechanisms may be involved in rendering immune protection. Furthermore, the molecular context of the immunizing antigen may influence the outcome of the fine specificity of T cells involved in immune protection. PMID- 2094597 TI - Immunity to falciparum and vivax malaria induced by irradiated sporozoites: a review of the University of Maryland studies, 1971-75. AB - The immunogenicity in adult male volunteers of sporozoites of Plasmodium falciparum and P. vivax was evaluated at the University of Maryland from 1971 to 1975. Inoculation of large numbers of sporozoites by mosquitos that had been X irradiated proved safe and well tolerated, and the sporozoites were rendered noninfective. Three volunteers were protectively immunized by this method, one against P. falciparum, one against P. vivax, and one against both species. Protection was species- and stage-specific, but effective against all strains tested within a species, and was reflected by a rise in titre of antibody to the circumsporozoite protein. PMID- 2094598 TI - Tooth splinting: a review of the literature and consideration of the versatility of a wire-composite splint. AB - The principles of tooth luxation splinting have been changed since the animal and human tests conducted in the early 1970s showed that masticatory stimulus promotes healing of luxated teeth and normally exerted occlusal forces are able to prevent and eliminate small resorption cavities on the root surface. It has also been shown that fixation of only one week is enough to achieve the clinical healing of repositioned teeth. Apart from esthetic and hygienic components, present-day demands on tooth fixation techniques also include ease of construction and removal and the use of devices which allow slight movement of the fixed teeth. This paper presents the history of tooth splinting, our present day knowledge of the subject, and introduces various splinting techniques. The wide range of indications for a flexible wire-composite splint are analyzed more thoroughly. PMID- 2094599 TI - Evidence for an inhibitor of osteoclast attachment in dentinal matrix. AB - The ability of osteoclasts to colonize in vitro different preparations of dentin extracted with guanidinium hydrochloride (GuHCl) was studied in order to establish morphological evidence for an extractable inhibitor of osteoclast spreading within dentin. Osteoclasts were isolated from neonatal rats and seeded onto pieces of fully mineralized dentin, demineralized dentin and predentin extracted with GuHCl. Osteoclasts were also seeded onto unextracted tissues. The results were evaluated with scanning electron microscopy. Osteoclasts colonized and resorbed fully mineralized dentin, whereas clastic cells were not observed on unextracted demineralized dentin and predentin. In contrast to this, osteoclasts attached and spread on demineralized dentin and predentin extracted with GuHCl. It was concluded that the non-collagenous organic component of dentin contains an extractable inhibitor of osteoclastic attachment and spreading. It is tempting to speculate that the inhibitor may be responsible for the naturally occurring resistance of dentin to resorption. PMID- 2094600 TI - Traumatic injury to maxillary incisor teeth in a group of South Wales school children. AB - This study examines, from photographic records, the prevalence of accidental damage to maxillary incisor teeth in a group of 968 11/12-year-old South Wales school-children; 15.3% showed evidence of trauma ranging from enamel fractures or discolouration to actual loss of a tooth. Boys (19.4%) showed a higher prevalence of trauma than girls (11%). Maxillary central incisors were the most at risk from trauma, with coronal fractures being the most commonly sustained injury. Those subjects who showed evidence of trauma had an statistically (p less than 0.001) but not clinically significantly greater overjet than did those who had none. The percentage of subjects suffering trauma increased significantly with increasing overjet, but lip incompetence did not affect the prevalence of accidental damage. Though statistically unsupported due to the small numbers involved in this cohort, it appeared that the rougher nature of boys activities and their more active participation in sports were of greater importance than the magnitude of their overjet in determining whether their teeth were at risk from trauma. In contrast, it was the magnitude of the overjet which was the dominant factor in girls. Despite the wide availability of relatively simple means of restoration and, in the majority of cases, regular dental examinations, only 14.8% of traumatised teeth had received treatment at this age. PMID- 2094601 TI - Prevalence of previous endodontic treatment, technical standard and occurrence of periapical lesions in a randomly selected adult, general population. AB - A random sample of 967 subjects selected from the total population in a Swedish county were examined radiographically regarding prevalence and quality of endodontic treatment and occurrence of periapical lesions. The relationship between the technical standard of endodontic treatment and the occurrence of periapical lesions was also analyzed. Of the selected individuals, 95% attended examination (751 dentate and 169 edentulous individuals). Of the 17,430 teeth examined, 1,492 (8.6%) were endodontically treated. Approximately 70% of the treated root canals were inadequately obturated; 10% showed excess of root filling beyond the apex. The prevalence of periapical lesions was 2.9%, and 24.5% of the endodontically treated roots demonstrated periapical lesions. Root fillings ending more than 2 mm from apex had a significantly lower frequency of periapical lesions than root fillings ending within 2 mm of the apex. No difference in the frequency of periapical lesions was found between properly and improperly obturated root canals. Excess of root filling material beyond the apex was related to a significantly higher frequency of periapical lesions. PMID- 2094602 TI - Vertical root fracture and dentin deformation in curved roots: the influence of spreader design. AB - The effect of lateral condensation using different tapered spreaders was evaluated. Curved mesiobuccal roots of maxillary molars were step-back prepared. Strain gauges applied to the root surfaces measured dentin deformation (distortion) during controlled lateral condensation with either fine finger or D11 spreaders. After obturation, roots were cross sectioned and analyzed under the stereomicroscope to detect the presence and pattern of fractures. The results showed no statistical difference between spreader designs as to mean distortion and the incidence of fractures; however several specimens in the D11 group showed high root distortion measurements. When fractures occurred, there were no consistent patterns of fracture in either spreader group. In conclusion, although there were no significant differences in mean deformation or fracture incidence in curved roots between the spreaders, the roots showing high deformation readings in the D11 group may be more susceptible to future vertical root fractures. PMID- 2094604 TI - Unusual case of general pulp calcification (pulp stones) in a young Greek girl. AB - An unusual case of generalized pulp calcification is reported in a 14-year-old Greek girl. Radiographic examination revealed large pulp stones in all permanent teeth located in the pulp chamber and sometimes extending to the coronal portion of the root canal. The patient's dental, medical and family history, as well as the findings from the clinical examination were non-contributory. Biochemical analysis of one pulp stone removed from the right maxillary central incisor revealed large amounts of urates, proteins and phospholipids, but a blood test of the patient showed no metabolic disturbance. Therefore, it is suggested that this unusual case may be of idiopathic origin. PMID- 2094603 TI - Trauma of treatment failure: a case report. AB - A large overjet is a well-recognised predisposing factor to traumatic injuries of upper incisor teeth. In order to reduce this risk factor, early reduction of an increased overjet has been recommended. This was attempted, but unfortunately was unsuccessful and further trauma resulted in loss of the upper central incisor teeth. PMID- 2094605 TI - Prostate cancer: new approaches to endocrine therapy. Proceedings of a symposium. Amsterdam, The Netherlands, 13-16 June 1990. PMID- 2094606 TI - The pharmacokinetics of Casodex in prostate cancer patients after single and during multiple dosing. AB - The pharmacokinetics of Casodex have been investigated in patients with prostatic carcinoma following single oral doses of 10 mg, 30 mg and 50 mg and during daily administration at these dose levels. Casodex displays prolonged absorption following a single dose, with peak plasma concentrations observed at up to 8 h for doses of 10 mg and 30 mg and up to 48 h for the 50 mg dose. The area under the plasma concentration-time curve increased linearly with dose, and Casodex was eliminated slowly from plasma (t1/2 about 6 days). During daily administration, Casodex accumulates about 10-fold in plasma at all dose levels; this is consistent with its long plasma elimination half-life, estimated by curve fitting of these multiple dose data to be 7-10 days. Trough plasma concentrations increased linearly with dose after both single and multiple dosing, achieving mean values of 1.80, 6.89 and 9.33 micrograms/ml for the 10 mg, 30 mg and 50 mg dose levels, respectively, after 12 weeks' dosing. Neither efficiency of renal function nor age had any apparent effect on the pharmacokinetics of Casodex. The pharmacokinetics of Casodex make it ideally suited to once-daily administration. PMID- 2094607 TI - The response of advanced prostatic cancer to a new non-steroidal antiandrogen: results of a multicenter open phase II study of Casodex. European/Australian Co operative Group. AB - Casodex is a non-steroidal antiandrogen which shows marked peripheral selectivity in animals. As an antiandrogen, it has been shown in a dose ranging and an open phase II study to have fewer side-effects than traditional non-steroidal antiandrogens and to be very well tolerated. In the open phase II study, the 50 mg dose was used in 127 evaluable patients who have been treated for up to 1 year. Overall response (i.e. partial response [PR]) was 50% with a further 33% showing stabilization of disease. PMID- 2094608 TI - Casodex: preclinical studies. AB - Antiandrogens are effective drugs in the treatment of advanced prostatic cancer. The main problems associated with their use are their short half-lives, leading to fluctuating serum levels, and their non-selectivity, which leads to increases in serum LH and testosterone through centrally-mediated actions. Casodex is a pure, potent antiandrogen which, in pre-clinical studies, has been shown to have a long half-life and a high degree of peripheral selectivity. Casodex is as effective as surgical castration or medical castration with Zoladex in inhibiting the growth of a transplantable Dunning prostate tumor in rats. These properties suggest that Casodex, given once daily, would be an effective and well-tolerated monotherapy for advanced prostatic cancer. PMID- 2094609 TI - [Psychosomatic dermatology]. AB - An appreciative cooperation among dermatology, clinical psychology and psychology and psychiatry is necessary and useful. By selected facts interactions between central and autonomous nervous system on one side and the immune system on the other side were described. As far as the neutrocutaneous interrelations are concerned the cutaneous stimulation appears to be an important factor for the physical and physiologic development. In addition, the skin communicates to the environment and other people. Therefore, it plays a role in the social integration. Psychiatric diseases can affect the skin (e.g. delusions of parasitosis in schizophrenia). On the other hand primary skin diseases such as psoriasis, atopic dermatitis, acune vulgaris, chronic idiopathic urticaria and alopecia areata may induce psychologic features. The characteristics of the personalities of dermatological patients are discussed. The psychodiagnostics (personal interview, questionaires) is followed by psychotherapeutic procedures such as personal consultations, treatment in groups, hypnosis and autogenous training. Our experiences in the psychodiagnostics and treatment are briefly reported. Finally, psychotropic drugs-antipsychotic, anti-depressant, antianxiety, and hypnotic agents - may be useful as an adjunct in the management of dermatologic disorders, if applied under precautious indications. PMID- 2094610 TI - Atypical iatrogenic presentations of molluscum contagiosum. AB - Description of two patients with atypical linear eruption of molluscum contagiosum in the places previously treated with iontophoresis of hydrocortisone for Bell's palsy, and with radiotherapy for malignant granulomatosis. The causal nexus of the treatment used previously and the appearance of described changes is considered. PMID- 2094611 TI - [Histotopochemical quantification of glycosaminoglycans in melanomas and the surrounding epidermis]. AB - 15 cases of human malignant melanoma were studied and classified into 5 superficial speading (SSM), 5 nodular melanomas (NM), and 5 melanoma metastasis (Met). The tissue was fixed with formaldehyde and cetylpyridium chloride (CPC). Glycosaminoglycans (GAG) or proteoglycans respectively were characterized by Alcian blue staining following the method of critical electrolyte concentration (CEC) (Scott, Dorling 1965) and by testes hyaluronidase. The staining intensities were quantified by a Leitz MPV photometer microscope in basement membranes (BM) and tumor septa. Tumor septa, which may be looked on as correlates of epithelial BM material, show increased straining intensities as compared to the normal BM (nBM) around the tumor. It is concluded from the sensitivity to testes hyaluronidase and the straining pattern that these are caused by increased straining of GAG of the type of chondroitin sulfates and possibly of dermatan sulfate while unsulfated GAG are rather decreased. The GAG pattern in BM in SSM shows characteristics of tumor septa and of nBM as well. The staining of the tumors shows higher intensities than that of all structures in the normal skin. It is concluded that increasing malignancy is accompanied by increasing changes in GAG which can be quantified by the method used topohistochemically discerning the healthy tissue from malignant structures. PMID- 2094612 TI - [History of leprosy in Erfurt]. AB - In Erfurt, one of the greatest towns of Germany in the middle ages, the leprosy rules from the beginning of the 13th to the beginning of the 17th century: a appearance, which was then typical for the development of this malady in Germany. The leprosy-patients was isolated in special hospitals. Her number vacillated between four and two. PMID- 2094613 TI - [Dermatologic memorial calendar 1990]. PMID- 2094614 TI - [Again about the therapeutic effect of hyperthermia in psoriasis]. PMID- 2094616 TI - [Critique to a report of the British Medical Association: nuclear attack: ethics and selection of victims]. PMID- 2094615 TI - [Nuclear threat in medicine]. PMID- 2094617 TI - [Current range of occupational medicine in chemical environments]. PMID- 2094618 TI - [Epileptic seizures as initial symptom of intracranial tumors. A prospective study in adults]. AB - A prospective study of 125 patients with late-onset epileptic crisis: Group G I with 65 cases between 20 and 50 years of age, and Group G II, including 60 patients older than 50 years at the time of the first crisis. Brain tumors were diagnosed in fourteen cases, four (6.1%) in G I and ten (16.6%) in G II. In decreasing order of frequency, the ictal pattern was tonic-clonic, status epilepticus, partial simple, partial complex and "drop-attacks". The lesions were located as follows:frontal in seven subjects, parietal in four, multiple in two and temporo-basal in one. Histologically, the tumors were three meningiomas, two gliomas, one astrocytoma, and three metastatic lesions. These findings agree with those of other series, in terms of predominant type of crisis, site and histologic type; but they differ in the age of first symptoms, and in the fact that tumors occupy only a third place as cause of epileptic crisis. PMID- 2094619 TI - [The heart in various connective tissue diseases]. AB - In this study is presented the experience of 294 patients with different connective tissue diseases such as: a) rheumatoid arthritis, b) systemic lupus erythematosus, c) ankylosing spondylitis, d) progressive systemic sclerosis, e) dermatomyositis-polymyositis and f) mixed connective tissue disease. All these patients were studied prospectively during the last eight years through non invasive methods to detect cardiovascular complications. The connective tissue diseases can provoke inflammation and fibrosis in any of the diverse cardiac structures, with the consequent complications. These alterations are frequent, with a high degree of morbidity, and have a direct relationship with the severity and chronicity of the primary connective tissue disease. Some of these patients respond favorably to cardiological and anti-inflammatory management, while others are refractory to such treatments. The prognosis of the observed complications in these patients depends in great part on the development of the basic rheumatic disease. This kind of patients should be studied systematically from the cardiological view point, so as to detect these complications as early as possible. PMID- 2094621 TI - [Serial vision of the history of science and society]. PMID- 2094620 TI - [Early respiratory function disorders secondary to tobacco smoking]. AB - The volume of isoflow (VisoV) in 29 asymptomatic smokers with normal radiographic and pulmonary function studies was studied, with the purpose of investigating the presence of early alterations of the transitional airways in a group of 256 chronic smokers. The VisoV was measured using a body test plethysmograph, and two flow-volume curves with air and with helium were performed. 13 out of the 29 subjects (45%) showed an abnormal VisoV of between 17 and 39 per cent (normal 0 10%). This findings suggest that smoking initially damages the small transitional airways and that VisoV is an useful procedure for investigating early damage in this zone. PMID- 2094622 TI - [Nutritional status of pre-school children and women in Mexico: results of a probabilistic national survey]. PMID- 2094623 TI - [Risk factors associated with neural tube defects: exposure during the first trimester of gestation]. AB - The neural tube defects (NTD) are a group of malformations of multifactorial etiology. Their high incidence in Mexico and the etiologic heterogeneity observed in several studies, prompted the present investigation with the main objective of looking for risk factors associated to NTD. We analyzed maternal exposure during the first trimester of pregnancy to different environmental factors, such as acute or chronic illnesses, immunizations, smoking, alcoholism, maternal or paternal occupation and exposure to chemicals. The sample include 360 patients with anencephaly, 249 with spina bifida and 44 with encephalocele, ascertained from a total of 230 635 live births and 4,020 stillborns, studied in the Mexican program of Registro y Vigilancia Epidemiologica de Malformaciones Congenitas Externa. Of the risk factors considered, significant differences with the control group were found for anencephaly in relation to maternal viral upper respiratory infection, hyperthermia, ingestion of analgesics, antiemetics and paternal occupation. In the case of spina bifida, significant differences were found only for viral upper respiratory infections. PMID- 2094625 TI - [Spring conjunctivitis]. PMID- 2094624 TI - [Current treatment of leprosy]. PMID- 2094626 TI - [Everything in Jose Maria Velasco is natural history]. PMID- 2094627 TI - [Charles Anthony Hufnagel. 1916-1989]. PMID- 2094628 TI - [Screening and identification of apolipoprotein CIII cDNA clones from human liver cDNA library and preparation of apolipoprotein CIII cDNA probe from the clones]. AB - Four of positive clones were obtained by three runs of screening the cDNA library of human liver with rabbit antihuman apolipoprotein (apo) CIII IgG. One of them was identified to be the positive clone of apoC III cDNA by restriction endonuclease map studies of the cDNA insert fragment and by Western blot analysis of the expression products. The apoCIII cDNA-gamma gt11 recombinant DNA prepared from the positive clone can be used in RNA-dot blot analysis as apoCIII cDNA probe. And the apoCIII cDNA clone can be also used to produced apoCIII peptide under the induction of isopropyl-beta-D-thiogalactoside. The apoCIII peptide, after purification, has a lot of use in further studies. PMID- 2094629 TI - [Effects of high carbohydrate and high fat diet on plasma apolipoproteins AI, AII, B100, CI, CII, CIII and E in normal and hypertriglyceridemic humans]. AB - Effects of high carbohydrate (CHO) and high fat diet on plasma apolipoproteins (apo) AI, AII, B100, CI, CII, CIII and E were assessed in 10 healthy subjects and 10 patients with endogenous hypertriglyceridemia. High CHO diet consisted of 80% CHO, 5% fat and 15% protein of total calories, and high fat diet consisted of 40% CHO, 45% fat and 15% protein. After 5 days normal diet (60% of total calories from CHO, 25% from from fat and 15% from protein), the subjects studied received sequentially high CHO diet and normal diet for 5 days and high fat diet and normal diet for 5 days. Fasting blood samples were drawn on days 1, 3, and 5 of high CHO and high fat diet period, and 5 days after taking normal diet. Results showed that fasting plasma apo AI slightly decreased (P less than 0.01) on day 3 of the high CHO diet period and slightly increased (P less than 0.01) on day 3 of the high fat diet period, plasma apo AII increased after intake of high CHO diet, but no changes were observed after the subjects were placed on high fat diet. Fasting plasma apo B100 decreased (P less than 0.001) in hypertriglyceridemics on the 3rd day of the high CHO diet, but no differences were noted in normal subjects on the same diet. On the 3rd day of the high fat diet period, apo B100 increased (P less than 0.01) in normal subjects, but no changes were found in hypertriglyceridemics. Apo CII and CIII levels declined during the high CHO diet period but increased in normal subjects after intake of high fat died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094630 TI - [DNA hybridization and identification of Leptospira serogroup icterohaemorrhagiae with Leptospira recombinant DNA probes]. AB - Two recombinant DNA probes-PLIpso1 (15kb) and PLIEc34 (4kb), derived from Leptospira serovaricterohaemorrhagiae genomic libraries, were applied for the hybridization and identification of 13 strains of Leptospira in serogroup icterohaemorrhagiae. Difference in hybridization signal in combination with the banding pattern provide a good way for identification of serovars and strains. The recombinant DNA, specific to L. serogroup icterohaemorrhagiae, hybridized with a limited number of DNA fragments which had been digested by several restriction endonucleases. The less complex banding pattern and higher sensitivity facilitate characterization of various serovars and strains in serogroup icterohaemorrhagiae. In general the DNA patterns recognized by both probes have extensive genomic homology in same serovar (but still can distinguish strains in same serovar by some unique bands) and apparent difference in various serovars (especially serovars naam, nanxi and honghe). The results indicated that Southern blotting with recombinant DNA probe might provide tools for identification, characterization and analysis of leptospira. PMID- 2094631 TI - [The study on genome size of leptospires]. AB - Determination of genome size is very important in genetic studies and the molecular cloning of leptospires. With pulsed field gel electrophoresis (PFGE), which can be used in the analysis of large DNA molecules, we studied the genome size of leptospires and analysed it with rare cutter restrict endonuclease Not I. The PFGE system used was CHEF-DR II which produced parallel bands in agarose gel. The results showed that the genome size of leptospires was 2000kb and there was no dramatic difference between the 5 strains of 2 genus leptospira. Rare cutter Not I digestion of genome DNA of leptospira resulted in 11 bands and its bands pattern was quite different from that of E. coli, S. choleraesuis, S. typhimurium, and S. dysenteriae genome DNA. It is thought that more information can be obtained about leptospiral DNA with PFGE technique. PMID- 2094632 TI - [Effect of phospholipase A2 on pancreatic parenchymal necrosis in acute pancreatitis in rats]. AB - The effect and mechanism of phospholipase A2 (PLA2) on pancreatic parenchymal necrosis in acute pancreatitis (AP) in rats were studied. Normal saline (NS), PLA2, phosphatidylcholine (PC), and PLA2 mixed PC were respectively injected into the biliopancreatic duct of the rat. The mixture of PLA2 and PC was found to result in necrotizing AP in the rat in 12 hours after injection of the reagent. The lysophosphatidylcholine (LPC) percentage in the amount of PC and LPC and the extent of pancreatic necrosis in this group increased much more significantly than those in other three groups (over about 4 and 15 times). There is evidently positive correlation (r = 0.9001, P less than 0.01) between LPC percentage and necrosis extent. The intraductal injection of PLA2, as well as NS or PC, failed to induce severe morphological changes in the pancreases. These results suggest that PC in bile is necessary in the pathogenesis of biliary pancreatitis and that LPC originated from bile PC by PLA2 may be the initiator in pancreatic parenchymal necrosis in AP. PMID- 2094633 TI - [The establishment of hemorheological data base and its applications]. AB - This hemorheological data base was established with an Apple II computer. The covering technique was applied to deal with its lacks of memories. This data base had a mutual administration system and complete managing functions including inputting, inquiring, printing, transferring, revising functions and so on. More than twenty hemorheological parameters involving apparent viscosities of whole human blood, plasma viscosity, viscoelasticity and thixotropy indices, were saved in the way of paging mode. Meanwhile, this data base had a common mathematical statistics system in recently medical use. It included monovariable linear and nonlinear regressions, t-test, multiple linear regression, cluster analysis etc. Therefore, this data base can be conveniently utilized to analyze the hemorheological data comprehensively. Besides the establishment of normal hemorheological indices, this data base equipped a primary method of quantitative diagnosis through hemorheological indices, it gave a new method to diagnose some diseases and to observe their curing process. PMID- 2094634 TI - [Expression of Pre-S1 and Pre-S2 in serum of patients with chronic type B hepatitis]. AB - To study the expression of Pre-S1 and Pre-S2 and gene-encoded proteins of the hepatitic B virus, we investigated serum from 11 patients with chronic type B hepatitis in various phases, Pre-S1 and Pre-S2 proteins were detected by the monoclonal antibody-based enzyme method, the markers of active viral replication were determined with the presence of HBV-DNA and HBeAg. It was found that Pre-S1 was present in the serum of 3 patients with viral replication as well as of 6 out of 8 cases with no evidence of viral replication, Pre-S2 in the serum of 2 out of 3 patients with active viral replication as well as 4 out of 8 cases with no evidence of viral replication. The similar results also appeared in patient's serum in various phases. The data suggest that there is no correlation between the presence of the Pre-S1 or Pre-S2 proteins and active viral replication during the course of chronic type B hepatitis. PMID- 2094635 TI - [Comparative study of Campylobacter pyloridis and Campylobacter jejuni under electron microscope]. AB - Specimens were made by preparing the ultrathin sections after negative staining and ruthenium red staining. The specimens were observed under electron microscope. Results revealed that the shapes of Campylobacter pyloridis (Cp) and C. jejuni (Cj) were similar, but distinctive differences in their structures were observed. Cp had one to five sheathed flagella at one end with bulbous tips. Cj had only one unsheathed flagellum on each end without a bulbous tip. The cell body of Cp was longer than that of Cj. A layer of thick and dense delicate filament-like substance was attached to the surface of the cell body of Cp in the ultrathin sections with ruthenium red staining, in the case of Cj only a little of such a substance could be noted. PMID- 2094636 TI - [A simplified polygraphic method for studying sleep in the rat]. AB - Experiments were performed on 10 healthy Wistar rats with chronically implanted electrodes for the recording of electrocorticogram (ECoG), electro-oculogram (EOG), and electromyography (EMG). All the rats were prepared for the implantation of recording electrodes under 5% Ketamine (100 mg/kg i.p.) anesthesia. Four to six days after operation, the rat was put in an apparatus which was designed specifically sensitive to detect the movement of the animal without electrode on the body so that electroactogram (EAG) could be recorded readily. One group of experiment animal (n = 5), recorded ECoG, EAG, EOG and EMG simultaneously, was compared to another group (n = 5), recorded ECoG and EAG simultaneously. The results of experiments indicate that the ECoG, recorded from the the mesial frontal and occipital areas, have certain characteristics during different sleep phases, and the characteristics for classifying sleep phases by the two kinds of somnopolygram are similar. Therefore, simultaneous recording of the ECoG and EAG can be used to discriminate the sleep phases in the rat. In this way, the somnopolygraphic recording method for studying sleep in the rat would be simplified. PMID- 2094637 TI - [Determination of MMTp in 628 normal children and adolescents with "convenient calculation"]. AB - According to the principle of linear character of each 10% FVC segment on the FVC t curve proposed by Jordanoglou, the slope of each segment is nearly equal to 0.1 FVC/2 MMTp. Then MTTp approximately 0.1 FVC/2Vp. The calculations of MTTp at high, middle and low lung volumes are MTT20-30% = 0.1 FVC/2V75, MTT45-55% = 0.1 FVC/2V50, and MTT70-80% = 0.1 FVC/2 V25. The MTTp of 628 cases of normal children and adolescents aged 6-19 yr. was measured by this method. In comparison with the direct method, the results showed that there was no significant difference between the 2 methods. The regression equations built with age as an independent variable showed a good correlation. Obviously, this method is easily performed, and is suitable for the wide use of MTTp. PMID- 2094638 TI - [Inhibiting effect of mitoxantrone on cell cycle progression of Chinese hamster ovary cells]. AB - The effect of Mitoxantrone, a Potential anticancer chemotherapeutic agent, on the cell cycle progression of Chinese Hamster ovary (CHO) cells was investigated by microspectrophotometry. CHO cells incubated with the agent for either 30 min or 24 h were inhibited, to various degrees, from proliferation. The inhibition appeared in dose dependent fashion. A 10-fold dose of the drug was required for the 30 min group, as compared to the 24h group, to develop an equivalent inhibiting effect. When exponentially growing cells were treated with Mitoxantrone for 30 min, washed free of drug, and cultured in fresh medium for another 23.5 h a dose of 0.01 micrograms/ml had little or no effect on the distribution of CHO cells throughout the cell cycle at any point. However, a dose of 0.10-1.00 micrograms/ml was sufficient to cause a decrease of cells in G1 and an accumulation of cells in G2. Block cells had abnormally large nucleus. PMID- 2094639 TI - [A study on pharmacokinetics of 3H-mitoxantrone in experimental animals]. AB - Mitoxantrone (DHAQ) we studied is a new semisynthetic antitumor drug prepared in China. This paper reports the pharmacokinetic studies of 3H-mitoxantrone in mice by liquid scintillation. The results showed that the decline of radioactivity in the plasma was a biphasic curve after intramuscular and intravenous injection in rats. The adsorption of 3H-DHAQ was ready and complete after intramuscular injection, it was widely distributed in body tissues. The concentration order of various organs was liver greater than intestine greater than kidney greater than lung greater than heart greater than muscles greater than brain. The elimination of the drug was slow, T1/2 was 42.56 h. In 72 h after administration the cumulative excretion of radioactivity in urine was 7% of the total dose, while that in feces was 43%. The main forms of the drug in urine were its metabolites. PMID- 2094640 TI - [Studies on the toxicity of a new synthetic drug SC1001-aminum]. AB - SC1001A is a new sedative, hypnotic and anti-epileptic drug. Screening for possible mutagenicity of the agent consisted of a battery scheme of short-term mutagenic tests with different hereditary detecting end points. Three assays were with in the scheme: Ames test (for detecting gene mutation in vitro), micronucleus test (for detecting chromosomal aberration in vivo) and CHL (Chinese hamster lung cell line) test (for detecting chromosomal aberration in vitro). In addition, a routine teratogenicity study on SC1001A was carried out in mice. They were given daily at 3-dose levels (exposed to up to 33% of the LD50 by gastric incubation from the 6th through the 15th day of gestation. SC1001A gave uniformly negative results in all three mutagenic assay systems. Results of the teratogenic experiment showed that only the pregnant rate in bred mice in the moderate dose group and the mean maternal body weight gain of the dams during gestation in the low dose group were significantly lower than those in the corresponding control group. A clear dose-response relationship was not demonstrated. All dose levels of SC1001A used caused no adverse effects on the number of survival fetuses per litter, growth or development of the fetal mice. No malformations in the external appearance, of the internal organs and of the skeletal systems in fetal mice were observed. The above-mentioned results indicated that SC1001A induced neither gene mutation nor chromosomal damage both in vitro and in vivo. There was no evidence of teratogenesis. Therefore, it is estimated that SC1001A is probably comparatively safe as a pharmaceutical product for human beings in usual dosage. PMID- 2094641 TI - [Study on the coated carbon PVC membrane selective electrode of aconitine]. AB - Coated carbon PVC membrane selective electrode of aconitine was prepared with the Aconitine-tetraphenylborate ion-associate complex as the electroactive material. The electrode showed a linear response to aconitine within the concentration range 1.0 x 10(-2) - 5.0 x 10(-5) mol/L. The limit of detection was 6.3 x 10(-6) mol/L and the slope of the electrode was 57.6 mV/decade. The authors established a basis and a method for the control of content limit of aconitine in Shen Fu Injection with this electrode. PMID- 2094642 TI - [The effect of China-made amrinone on myocardial infarction and arrhythmia in dogs]. AB - Six dogs underwent 15 min left anterior descending (LAD) coronary artery occlusion (CAO) with 1 hour's reperfusion for 3 times. Fifteen min after CAO (control), CAO during amrinone (Amr), and CAO during isoprenaline, sigma ST (mV) and ST (mV) were 66 +/- 26 and 8 +/- 2.72 +/- 61 and 9 +/- 4.90 +/- 48 and 11 +/- 6 respectively, 24h after LAD CAO, dP/dt max (kPa/s) and HR (heart beats/min) were 483 +/- 93 and 211 +/- 36 respectively. Intravenous Amr by 1, 5, 3 and 6 mg/kg increased dP/dt max to 630 +/- 79, 583 +/- 116 and 500 +/- 148; HR to 223 +/- 44, 232 +/- 45 and 239 +/- 54; and also decreased SBP, DBP and LVEDP. Amr caused neither change in percentage of non-sinus beats, nor ventricular fibrillation. These results suggested that in myocardial infarction and arrhythmia, Amr could still be of positive inotropic effect. Amr worsened myocardial infarction in nonfailing heart, but it did not aggravated arrhythmia after myocardial infarction. PMID- 2094643 TI - [Studies on immunoregulation and hypersensitivity of secretary otitis media]. AB - Sixty patients with secretary otitis media (SOM) and 50 control cases were studied for their cellular immunity and hypersensitivity. Most of patients revealed that total T or T cell subpopulations were below those of the control. Eighty percent of patients had high serum IgE level and 81.2% as Positive in intradermal skin tests on inhalant allergy, but only 51.7% of patients had clinical symptoms of allergy. It was found immunologically that SOM occurred more frequently in allergic patients and most of them had abnormality of immunoregulation, and that there was a subclinical allergy for some of the patients. Allergy might play a significant role in the etiology of this disease. Authors suggest that it is necessary for patients with SOM to have some tests and treatment of immunology. PMID- 2094644 TI - [Primary study on pathogenesis of Campylobacter jejuni enteritis]. AB - The invasiveness and heat-labile enterotoxin of 11 human strains of C. jejuni were detected in NIH mice inoculated with the C. jejuni strains; the methods of plate immunological hemolysin test and SPA-coagglutination test were employed. Ten strains of the bacteria invaded the intestine; 7 strains (45.46%) were positive in SPA-coagglutination test; and 4 (36.36%) produced enterotoxin. C. jejuni in Chengdu area possess multiple pathogenicity, e.g invasiveness and heat labile enterotoxin, but we did not find definitive correlations between the clinical manifestation and resource of strains. PMID- 2094645 TI - [Experiment study of adriamycin-induced nephrotic syndrome in rats]. AB - A single intravenous injection of adriamycin (5 mg/kg) into rats caused the full expression of nephrotic syndrome characterized by heavy proteinuria, hypoalbuminemia, hypercholesterolemia, thoracic and ascitic fluid; swelling and fusion of foot processes of epithelial cells could be observed under electron microscope; histologic examination by light microscopy did not reveal any significant changes. The features of the model in clinic and pathology were very similar to those described humans with minimal change nephrotic syndrome. The observation in the various periods of the model indicated that the ultrastructure changes in epithelial cells occurred prior to the onset of proteinuria. The present study, combined with the results of quantitative analysis with image analyzer for alteration of glomerular polyanions, suggests that both morphologic changes and proteinuria may be the consequence of a common primary event that is the loss of glomerular polyanions. The model has the advantages of being rather simple and convenient; providing lasting proteinuria and pathological changes in stable condition; and having high reproducibility and a sufficient supply of the drug used. PMID- 2094646 TI - [The evaluation of thyroid suppression test in predicting the outcome of Graves' disease treated by short-term antithyroid drugs]. AB - One hundred and fifteen new patients with Graves' hyperthyroidism were received thyroid suppression test after cessation of 6 month course of drug therapy. The results of follow up for another 12 months were that one of them had lost, 48 cases were in remission, and 66 cases had relapsed. The present study shows that thyroid suppression test, including the 4th, 6th and 24th hour suppression rates, is useful in predicting the outcome of drug therapy. The effect of 6th hour suppression rate is better than that of 24th and 4th hours, with 75.8% sensitivity, 75.0% specificity and 75.4% accuracy when 30% of thyroid suppression rate is as out-off point which is decided by ROC curve. It is suggested that 6 hour 30% suppression rate is better than the traditional 24 hour 50% suppression rate in the prediction of outcome of drug therapy. PMID- 2094647 TI - [The measurement of umbilical artery flow velocity waveforms in normal late pregnancy by Doppler ultrasound]. AB - Doppler ultrasound was adopted in a study of fetal umbilical artery flow velocity waveforms in 81 cases of late pregnancies (28-41 gestational weeks). The peak systolic/end-diastolic ratio (A/B) and the Pourlot index were used as indices for assessing placental resistance. Both the A/B ratio (2.34 +/- 0.44) and Pourlot index (0.56 +/- 0.07) decreased while the gestational week was increasing, and they had a good correlation with the gestational week (r1 = -0.90, r2 = -0.93). The results indicated that the placental resistance became lower when the gestational week was increasing. This method has been documented a useful noninvasive technique for the exam of placental resistance. PMID- 2094648 TI - [An acute experimental study on the combinations of aluminum and fluorine in various ratios]. AB - The joint actions were assessed by four methods after male Wistar rats had been acutely intoxicated with nine proportional mixtures of Al and F. Strong antagonistic effects of Al on F were observed in the mixtures, in which the ratio of Al to F ranged from 0.8:0.2 to 0.1:0.9. The optimum ratio of Al to F for antagonism ranged from 0.3:0.7 to 0.1:0.9 without periorbital bleeding that was a regular finding in Al acute toxicity on the rat to be seen. When the amount of Al in the mixture was below 5% or above 90%, no antagonistic effect was shown. The kinetics on the absorption under the condition of Al and F existing simultaneously is still unknown, and warrants further investigation. PMID- 2094649 TI - Anthropometry of seated women during pregnancy: defining a fetal region for crash protection research. AB - An anthropometric description was developed for the fetal region of women at three, six, and nine months of pregnancy. This involved superimposing a fetal ellipse on abdominal and pelvic ellipses of seated women from a previous study. The data were developed for women of 5th, 50th, and 95th percentile size. The ellipses identify body contact zones on the side and front which would interact with the fetal region in a crash. The new information provides spatial characteristics of pregnant women for the development of test dummies, accommodating restraints, and friendly interiors and for enhancing crash protection. This research addresses the 342 deaths of pregnant women estimated to occur annually in motor vehicle crashes. PMID- 2094650 TI - Sensory alternation and vigilance performance: the role of pathway inhibition. AB - Posner's theory of pathway inhibition leads to the expectation that stimulus heterogeneity should attenuate the event rate effect and the decrement function in sustained attention. These predictions were tested through a sensory alternation procedure in which stimulation was shuttled between the auditory and visual modalities. Subjects detected slight reductions in the duration of recurrent flashes of light or bursts of white noise at two event rates (5 and 40 events/min) during a 50-min vigil. Consistent with the model, sensory alternation eliminated the event rate effect. It did not, however, moderate the decrement function. Although pathway inhibition can account for the effects of event rate, other factors are probably responsible for the vigilance decrement. PMID- 2094651 TI - The accuracy of implant master casts constructed from transfer impressions. AB - The accuracy of master casts fabricated from three impression techniques commonly used with the Branemark System was measured. Points placed in a metal surrogate model and onto master abutments were compared after abutments were transferred to stone casts using splinted and unsplinted impression coping techniques. The mean values and standard deviations of each of the reference points on 12 total casts were compared with the values for each point from the surrogate model. Values from techniques using splinted and unsplinted squared polymer copings as well as unsplinted tapered hydrocolloid copings were not significantly different from values recorded from the master surrogate model. Tapered hydrocolloid copings yielded a higher correlation to coordinate values on the master than unsplinted squared polymer copings or splinted squared copings. PMID- 2094652 TI - Immediate fixture placement: a treatment planning alternative. AB - The rationale and possible clinical applications of an immediate fixture placement technique are described. Although this concept may be a somewhat radical departure from the conventional mandibular protocol, there are significant potential patient benefits with no apparent change in anticipated fixture survival rates. A similar approach in the maxilla may be less practical with most presenting dentitions, but there is evidence that further research may make immediate fixture placement equally appropriate in this arch. PMID- 2094653 TI - Long-term follow-up study of osseointegrated implants in the treatment of totally edentulous jaws. AB - This study reviews the long-term outcome of prostheses and fixtures (implants) in 759 totally edentulous jaws of 700 patients. A total of 4,636 standard fixtures were placed and followed according to the osseointegration method for a maximum of 24 years by the original team at the University of Goteborg. Standardized annual clinical and radiographic examinations were conducted as far as possible. A lifetable approach was applied for statistical analysis. Sufficient numbers of fixtures and prostheses for a detailed statistical analysis were present for observation times up to 15 years. More than 95% of maxillae had continuous prosthesis stability at 5 and 10 years, and at least 92% at 15 years. The figure for mandibles was 99% at all time intervals. Calculated from the time of fixture placement, the estimated survival rates for individual fixtures in the maxilla were 84%, 89%, and 92% at 5 years; 81% and 82% at 10 years; and 78% at 15 years. In the mandible they were 91%, 98%, and 99% at 5 years; 89% and 98% at 10 years; and 86% at 15 years. (The different percentages at 5 and 10 years refer to results for different routine groups of fixtures with 5 to 10, 10 to 15, and 1 to 5 years of observation time, respectively.) The results of this study concur with multicenter and earlier results for the osseointegration method. PMID- 2094654 TI - Characterization of sterilized CP titanium implant surfaces. AB - Surface analysis techniques and in vitro biologic assays were used to characterize sterilized commercially pure titanium surfaces. Significant surface alterations were observed following sterilization treatments. These alterations led to decreased fibroblast cell attachment and altered cellular spreading phenomena compared to nonsterilized control surfaces. PMID- 2094655 TI - Variations in occlusal forces with a resilient internal implant shock absorber. AB - The importance of an internal shock absorber for implant prostheses has concerned many, primarily because the efficacy of a shock absorber to reduce stress has not been demonstrated in vivo. This study examined 15 subjects with unilateral distal extension single implant abutments attached to a single natural tooth abutment to assess the effect of a shock-absorbing element within the implant on occlusal force levels. Occlusal forces and bilateral occlusal similarity were examined using specially adapted research software for the T-Scan occlusal analysis system. The results indicate that there is a significant difference (P less than 0.011) between occlusal forces using an internal shock absorber (18 N) and a titanium internal element (30 N). PMID- 2094656 TI - Clinical evaluation of overdenture restorations supported by osseointegrated titanium implants: a retrospective study. AB - This paper reports the results of using osseointegrated titanium implants as abutments for overdenture restorations in the mandibles of 62 edentulous patients. All of these patients were edentulous for several years and required complete dentures. Six months after prosthodontic treatment, two implants (ITI, Straumann) were placed with consideration of the denture base and morphologic aspects of the mandibular residual ridge. The retention devices consisted of a bar connector or single ball-shaped precision attachments. Three or four implants splinted with a bar were placed in a control group of 11 patients. Attached keratinized gingiva (greater than or equal to 2 mm) surrounded approximately 48% of the buccal and 55% of the lingual implant sites. Evaluation after periods of 6 to 66 months postoperatively revealed good clinical results with five patients lost to recall in 1989. Two implants were lost after overdenture insertion. The findings suggest that two implants may adequately serve as retention for a mandibular complete denture and that attached gingiva surrounding the implants does not seem to be prerequisite for healthy function. PMID- 2094657 TI - CT scan standard reconstruction technique for reliable jaw bone volume determination. AB - Computed tomography can assist the surgeon in planning the exact three dimensional positioning of endosseous implants in the jaw bone. This study examined the reliability of three CT techniques: direct imaging (normal coronal and sagittal slices), standard reconstruction (based on axial slices), and multiplanar reconstruction and display (also based on axial slices). The three imaging techniques were used to estimate the bone height, bone width, and maximal implant length in six dissected human jaw bones. These jaws were then sawed perpendicular to their axis to enable measurement of real values for comparison. The sagittal and coronal slices frequently were overestimated, especially in the canine and premolar regions. The mean absolute deviation was 1.4 mm. Standard reconstruction offered the most reliable cross-sectional images, with a mean absolute deviation of 0.5 mm. The multiplanar reconstruction and display technique frequently demonstrated underestimations (mean absolute deviation was 2.3 mm). The standard reconstruction technique seems to be the method of choice in preoperative radiographic examination of patients before implant placement. PMID- 2094658 TI - Periotest method as a measure of osseointegrated oral implant stability. AB - Oral implant stability is essential for optimal function. Results obtained from the Periotest measurement of the stability of 204 commercially pure titanium implants, consecutively placed in 22 maxillae and 24 mandibles according to the Branemark procedure, are reported. Preliminary results suggest that the Periotest value of an oral implant is an objective and easily applied criterion for stability assessment. Since osseointegration is achieved gradually over time, this test may assist the clinician in deciding whether to extend the healing period before loading fixtures that seem clinically and radiologically integrated but give borderline Periotest values. PMID- 2094659 TI - Considerations in placement of implants through existing split-thickness skin graft vestibuloplasty: a case report. AB - Many edentulous patients who previously have undergone vestibuloplasty with split thickness skin grafting to improve denture stability and function seek additional help with dental implants. Problems encountered following the placement of four endosseous root-form dental implants in one such patient are presented. The anatomic and surgical considerations as well as methods available to circumvent these problems are discussed. PMID- 2094660 TI - Converting an implant-supported fixed prosthesis to an overdenture because of fixture loss: a case report. AB - A patient with a failed implant-supported prosthesis was treated with an immediate interim overdenture. After insertion of a bar modified from the prosthesis substructure, the patient was restored with an implant-supported overdenture. A bar soft liner retention system was used to aid retention and stability of the overdenture. PMID- 2094661 TI - Approach to the eighth five year plan, 1990-95. Planning Commission, Government of India. PMID- 2094662 TI - Diagnostic approach to stillbirths. PMID- 2094663 TI - Helping parents to face perinatal loss. PMID- 2094665 TI - Neonatal polycythemia--issues and current perspectives. PMID- 2094664 TI - Detection of fetomaternal hemorrhage. PMID- 2094666 TI - Tuberculosis in children. PMID- 2094667 TI - Pediatric tuberculosis pyramid and its fate with and without chemotherapy/chemoprophylaxis. AB - The latest available information on total and infectious cases of tuberculosis in the country and also large number of sputum positive cases being detected annually, particularly after the involvement of multipurpose workers in the primary health care programme for the control of tuberculosis, is presented. The consequences of the large pool of infectious cases in the population lead to spread of bacilli to children with development of primary infection in them. These children with primary infection, specially high risk group in infancy and early childhood, get serious complications of the disease. It may be emphasized that BCG vaccination cannot prevent the lodgement of tubercle bacilli in the lung but can only contain or restrict haematogenous spread. Inspite of increasing coverage of infants with BCG vaccination there are an increasing number of cases of intrathoracic tuberculosis, particularly various groups of mediastinal nodes. However, to a lesser extent haematogenous complications do occur in malnourished children, as BCG has a limited value in preventing serious complications in children with malnutrition. The clinical pattern of pediatric tuberculosis has also changed in vaccinated and partly or inadequately drug treated children. Hence, chemoprophylaxis/chemotherapy to prevent complications of primary infection has been tried. Even relatively privileged children in developed countries are reported to have complications of primary infection to an extent of 10 to 15%, as per the studies all over world. So preventive chemoprophylaxis, preferably with two bactericidal drugs, should be considered as the main strategy for controlling primary infection. Chemoprophylaxis with two drugs should be used as incidence of isoniazid resistant bacilli has increased. All concerned with child health should consider the strategy of treatment of primary infection in high risk children by chemoprophylaxis by starting a large multicentric trial both in urban and rural areas, as a part and parcel of primary health care intervention already in practice for cases of sputum positive pulmonary tuberculosis. PMID- 2094668 TI - Pediatric tuberculosis in immigrants to the United Kingdom from the Indian sub continent. AB - Tuberculosis (TB) is now an uncommon disease in the United Kingdom (U.K.) and its overall incidence is declining. However, the incidence of TB in immigrants from India, Pakistan, and Bangladesh (the Indian sub-continent, ISC) is much higher than in the native white population or immigrant groups from other areas, and this is so even for children of ISC ethnic origin born in the U.K. The clinical pattern of the disease also differs, extrapulmonary involvement being commoner in ISC patients than white patients. The epidemiology and management of TB in pediatric patients of ISC origin is reviewed and reasons for differences from other ethnic groups in the U.K. are discussed. PMID- 2094669 TI - The role of BCG vaccine in tuberculosis control. AB - The present communication deals with the various important issues about the BCG vaccine being using for the control of tuberculosis. The first issue is of BCG vaccine. BCG daughter strains, namely, French, Glaxo, Japanese and many others, inspite of minor differences evoke similar immune responses and none of the strains is superior to other. PMID- 2094670 TI - Immunologic and immunogenetic studies in rheumatic fever and rheumatic heart disease. AB - In order to evaluate all the important limbs of the immune system in the same patient population with rheumatic fever (RF) and rheumatic heart disease (RHD) cellular and humoral immune parameters as well as the immunogenetic profile in 265 North Indian patients with RHD were evaluated. They were studied for class in HLA antigens and 165 of them were also evaluated for the class II (DR locus) antigen profile. Data obtained was compared with 400 and 134 healthy controls respectively of the same ethnicity. Humoral immune parameters (Serum immunoglobulins IgG, IgA; Serum complement fractions C3, C4, C3d; circulating immune complexes and B lymphocyte numbers) and cellular immune parameters (total leucocyte and lymphocyte counts; T lymphocyte sub-populations--CD4, CD8 counts; lymphocyte migration inhibition to an extracellular streptococcal antigen, streptolysin 'O') were studied in 23 patients with RF, 21 patients with "inactive" RHD and 20 normal controls. Patients of RHD were noted to have an increased frequency of DR3 (P less than 0.001; Relative risk = 2.3) and a decreased frequency of DR2 (P less than 0.001; Relative risk = 0.3) as compared to the controls. Patients of RF had evidence of an altered regulatory T cell function (increased CD4/CD8 ratio) and decreased cell mediated immunity to streptolysin 'O'. An increased humoral immune response (increased B cell counts, elevated serum IgG, circulating immune complexes and C3d) was noted in patients of RF as well as "inactive" RHD. An integrated pathogenetic model with immune response associated antigens of the DR locus influencing selection of cardiac cross-reactive antigens by the antigen processing macrophages, an altered regulatory T cell function with decreased suppressor T cell activity leading to an abnormal immune response is proposed to explain the pathogenesis of RF. PMID- 2094671 TI - Epidemiology of pneumonia in rural underfives. AB - Rural underfives (5335) were followed for a period of one year from January to December 1987 for acute respiratory infections (ARI). Those affected with pneumonias were studied in detail to know the epidemiology. The children reported an attack rate of 0.29/child/year. Severe cases constitute 0.5%. Infants had higher attack rate (0.59/child/year), 47.7% of episodes occurred in infants and 87.7% occurred in children below 3 years. Males had a higher attack rate (0.32 vs 0.27). Mean duration of attack was 5.45 +/- 1.95 days. The attack rate was higher in winter. The case fatality rate was 1.26%. It was highest in neonates (10.7%) Females had higher case fatality rate than males (1.5% Vs 1.1%). Mortality was very high in severe cases. Case fatalities were high in seasons when the climatic change occurred, the highest being in autumn. PMID- 2094672 TI - Auditory brainstem responses (ABR) in neonates with hyperbilirubinemia. AB - The technique of ABR testing was applied to 25 infants with neonatal hyperbilirubinemia at levels exceeding that for exchange transfusion, in an attempt to study potential influence of bilirubin toxicity on the auditory brainstem pathway. The test was performed at a mean conceptional age of 40.4 +/- 0.6 weeks just after discharge. Twenty normal term neonates of comparable birth weights and conceptional ages, who had no hyperbilirubinemia, were also examined for comparison. Fifty six percent (n = 14) of the hyperbilirubinemic neonates had some abnormality in the ABR pattern, the major one being a transient increase in the threshold of wave V (7, fail-30; 5, fail-45). Wave V, however, was consistently present at 30 dBnHL click stimulus in all the normal neonates (pass 30; normal threshold). Further, mean ABR latencies (wave III, V) and 1-V interpeak latency (brainstem conduction time) were significantly prolonged in jaundiced neonates as compared with controls (P less than 0.01). ABR changes were strongly correlated with the serum bilirubin levels (P less than 0.001). On follow up retesting at 3 months, however, all infants were found to have normal ABR latencies and threshold. Neonatal jaundice was associated with significant transient aberrations of ABR, suggestive of a transient toxic brainstem encephalopathy. PMID- 2094673 TI - Perforated tubercular enteritis of childhood: a ten year study. AB - One hundred sixty seven children were operated at the Kalawati Saran Children Hospital for acute peritonitis during last 10 years (1978-88). Bowel perforation was seen in 123 cases. Nineteen cases had underlying tubercular enteritis. Preoperative diagnosis was usually difficult. The terminal ileum was affected in 12 and the jejunum in 5 cases. Multiple perforations were seen in 3 cases. Postoperative mortality was high (12/19) and usually attributable to their poor preoperative status. PMID- 2094674 TI - The diagnosis and management of MSUD in Saudi Arabia by using two different methods. AB - Plasma amino acid concentrations were measured in Maple Syrup Urine Disease (MSUD) infants using reversed phase high performance liquid chromatography (HPLC). The technique involved an automated data acquisition system and phenylisothiocyanate (PITC) pre-column derivatization. During a period of three years more than 14 cases of MSUD have been confirmed in our hospital suggesting an alarmingly high rate of incidence of this disease in the Kingdom as compared to the West. We present here a simple and reliable method of quantitating the branched chain and other amino acid concentrations in plasma samples of children with metabolic disorders. In addition, we also present a fluorimetric COBAS based enzymatic method for the rapid semiquantitative measurement of branched chain amino acids for a disease in which a prompt initial diagnosis is essential. PMID- 2094675 TI - Management of neonatal anemia in the delivery room. PMID- 2094676 TI - Multiple pleural masses--an unusual presentation of tuberculosis. PMID- 2094677 TI - Ocular malformation following ethambutol, rifampicin, isoniazide in the first trimester of pregnancy. PMID- 2094678 TI - Sex-role perceptions in chemically dependent subjects: adults versus adolescents. AB - Contrary to expectations, a study of 81 adolescent drug and/or alcohol addicts produced results quite similar to those found among an adult addicted population (Griffin-Shelley, 1986). On the Bem Sex-Role Inventory (Bem, 1974), these young people rated themselves, in descending order, Undifferentiated (43.2%), Masculine (23.5%), Androgynous (18.5%), and Feminine (14.8%). Despite their exaggerated "macho" and "seductive" attitudes and behaviors, which resemble their adult counterparts, chemically dependent adolescents suffer similarly from low self esteem and poor adjustment. Addictions appear to have already damaged these young people in areas of self-worth and sex-role perception. PMID- 2094680 TI - Chemical aversion treatment of alcohol dependence. II. Future research directions for the '90s. AB - Chemical aversion treatment is one of the most promising modalities currently available for treatment of alcohol dependence. This review highlights potentially fruitful areas for future investigational efforts and poses a number of specific empirical questions. Investigation of issues delineated in this report would advance understanding of pharmacological aversion therapy vis-a-vis utility and mechanisms of action. PMID- 2094679 TI - Human values and marijuana use. AB - The purpose of this study was to examine the relationship between prioritized rankings of human values among persons who either use or do not use marijuana. Discriminant analyses indicated that personal values are more important to marijuana users, while social values are more important to nonusers. Based upon the present study and previous research, the existence of a value orientation predisposing some individuals toward substance experimentation and use is suggested. PMID- 2094681 TI - Factors affecting alcohol consumption in black women. Part II. AB - An eight-variable model for understanding and predicting alcohol consumption in a sample of 289 African American women is evaluated using a structural equation methodology. We found that life events, physical health problems, and internalized racialism played important roles in accounting for variance in alcohol consumption. Marital status did not have the predicted inverse effect on alcohol consumption. While religious orientation did not have the expected inverse effect on alcohol consumption, it had an unexpected direct effect on internalized racialism, which had a direct effect on alcohol consumption. We found that the effects of socioeconomic status and developmental status on alcohol consumption were mediated through other variables specified in the model. Overall the model, which provided partial to complete support for five of eight hypotheses, provided a statistically adequate fit. PMID- 2094682 TI - Smoking and drinking: a review of the literature. AB - Smoking and drinking share many detrimental effects, some of which operate synergistically. Over 90% of alcoholic inpatients are smokers, with similar findings regarding outpatients. In the general population, the relationship between smoking and drinking appears positive but modest. Nicotine appears to facilitate ethanol consumption and vice versa. While ample theoretical viewpoints exist to explain the covariance of alcohol and cigarette consumption, conclusive data supporting one or another of these views are lacking. The assumption that alcoholics should be discouraged from quitting smoking as well as drinking is without empirical basis. Research should ascertain whether problem drinkers with greater positive association between alcohol and smoking benefit differentially from quitting both. PMID- 2094683 TI - Lessons from an English opium eater: Thomas De Quincey reconsidered. AB - Thomas De Quincey published his autobiographical Confessions of an English Opium Eater in 1821. The publication both fascinated and outraged its 19th-century readers. Heated debate followed on such topics as: the causality of opiate use; self-inflicted suffering and responsibility; the impact of availability and environment; therapeutic addiction; controlled use; the emergence of dependence; tolerance; withdrawal techniques; hazards; the impact of advertising. Many of these topics remain subjects of debate and causes for concern today. We would be well advised to study the questions and debates of a century and a half ago. PMID- 2094684 TI - Psychopathology and personality characteristics in different forms of substance abuse. AB - Sixteen opiate, 16 amphetamine, 34 cocaine, and 29 marijuana abusers were administered the Million Clinical Multiaxial Inventory and the SCL-90R symptom checklist at treatment admission. Results showed that the combined drug group had levels of psychopathology that were significantly higher than those of a normative psychiatric sample. The four drug groups differed significantly from one another on four scales of the SCL-90R, with the amphetamine group differing from the others on two of the scales. These findings reveal high levels of psychopathology and considerable heterogeneity of symptoms within and across groups of substance abusers at treatment admission. PMID- 2094685 TI - Needle-sharing practices and risk for AIDS transmission among intravenous drug users in Seattle. AB - Sharing of needles by intravenous drug users is known to be one of the major means for the transmission of the HIV virus into the general population. In Seattle, where liberal laws make acquisition of needles relatively easy, it has been assumed that needle sharing is not a significant problem. Results of a survey of 212 methadone maintenance clients demonstrated that needle sharing is quite prevalent among intravenous drug users in this area and that addicts fail to sterilize their needles between uses. Because the rate of HIV infection among Seattle's intravenous drug users is relatively low, immediate intervention efforts by public health authorities can prevent a rapid acceleration of the infection rate. PMID- 2094686 TI - A caveat: drug policy as factor of trends in trade and use of different substances. PMID- 2094687 TI - Co-operative research. PMID- 2094688 TI - Restorative proctocolectomy: the Irish experience. Irish Association of Coloproctology. AB - Between January 1982 and March 1990, 106 patients underwent restorative proctocolectomy in eight separate surgical departments. The indication for operation was ulcerative colitis in 86%, familial adenomatous polyposis in 12% and megacolon in 2%. The age at operation was 33 +/- 2 years (mean +/- sem) (range 15-55 years). There were no perioperative deaths. The principal causes of post-operative morbidity were intra-abdominal sepsis (15%), anastomotic stricture (10%) and intestinal obstruction (8%). Intestinal continuity has been restored in 99 patients. All were grossly continent, but 32% experienced occasional soiling. The mean stool frequency was 5/day and 1/night. The overall failure rate was 6%. Eighty-nine percent of patients were happy with the outcome. We conclude that restorative proctocolectomy is safe and provides acceptable functional results. It should be the operation of choice in most patients with ulcerative colitis or familial adenomatous polyposis. PMID- 2094689 TI - Early results with restorative proctocolectomy. AB - The first 25 restorative proctocolectomies (RP) performed by one surgeon since 1986 are reviewed. Ulcerative colitis (23) and idiopathic megarectum (2) were the indications for surgery. The initial seven patients had a submucosal proctectomy and transanal hand sewn pouch-anal anastomosis. Eighteen patients had a totally stapled RP. One patient with malignancy died from factors unrelated to surgery. Complications developed in eight patients after pouch-anal anastomosis and in four patients after ileostomy closure. There was one pouch failure due to pelvic sepsis. No pelvic sepsis has occurred following a stapled ileal pouch-anal anastomosis with defunctioning ileostomy. After a mean follow up period of 20.5 months all patients are continent (mean stool frequency = 4/day and 0.5/night). Soiling occurred in three patients who had a transanal hand sewn pouch-anal anastomosis. All patients in the stapled group have satisfactory control. Restorative proctocolectomy produces satisfactory operative and functional results which have improved as our experience has increased. PMID- 2094690 TI - Assessment of variables contributing to cyclosporine distribution in blood. AB - Factors which can account for the poor correlation between whole blood and plasma Cyclosporine (CsA) levels in patients on CsA prophylaxis are evaluated. The study took account of the influence of plasma separation procedures, and the sample haematocrit on CsA distribution in the blood of renal transplant patients (n = 35). CsA was measured using both specific and non-specific CsA radioimmunoassays. Significant negative correlations occurred between CsA distribution and the haematocrit, independently of the plasma separation procedure or the specificity of the assay. All results were lower when using the specific assay but a significantly higher percentage of CsA was measured in the plasma by specific assay compared to nonspecific assay when plasma was separated at both 22 degrees C (t-test, p less than 0.02) and at 37 degrees C, p less than 0.01). This may relate to the selective binding of CsA and its analogues by blood cells. This study is a prelude to the development of more consistent plasma separation procedures in the monitoring of this drug. PMID- 2094691 TI - The management of heart transplant recipients treated with cyclosporine in Ireland: monitoring of cyclosporine concentrations in blood. AB - Thirty seven cardiac transplants have taken place at the National Cardiac Centre in Ireland since 1985. Data is presented on three still-surviving male patients aged 19 to 42 who received cardiac transplants in 1985 and 1986. Circulating levels of blood cyclosporine were measured by high pressure liquid chromatography and radioimmunoassay; plasma creatinine and bilirubin were also measured. In one of these patients the distribution of cyclosporine in blood was measured by high pressure liquid chromatography in a long term study. For all three patients cyclosporine levels in blood were compared with the daily dose of cyclosporine and biochemical and histopathological parameters. PMID- 2094692 TI - Reactive airways dysfunction syndrome (RADS) due to chlorine gas exposure. AB - Reactive Airways Dysfunction Syndrome (RADS) has been described following exposure to various irritant gases. We describe a case of RADS occurring following exposure to chlorine gas and which has persisted at 6 years follow-up. PMID- 2094694 TI - Midland Health Board staff and impact of cuts. AB - An analysis of the 2,719 staff of the Midland Health Board at 31 December, 1988 was made, on the basis of work done. This showed that 7.4% of the staff were engaged on administrative work. The pay cost of the administrative staff was 5.2% of total remuneration and 3.3% of all direct payments made by the health board. Between January, 1986 and the end of 1988, staff numbers were reduced by 293 (9.7%). Of these, 189 (64.5%) were catering, housekeeping and maintenance staff. In the same period medical staff increased by 5 (3.3%), paramedicals increased by 11 (10.4%) and administrators were reduced by 12 (4.2%). PMID- 2094693 TI - Extra-amniotic prostaglandin induction of labour supplemented with intravenous oxytocin following fetal death in utero. AB - A five year retrospective study (1984-1989) was undertaken on 24 consecutive patients with fetal death to ascertain the efficacy, side effects and complications associated with a combination of extra-amniotic prostaglandin E and intravenous oxytocin to induce labour. Six patients with primigravidae and eighteen multigravidae with inductions carried out at gestations ranging from 16 to 37 weeks (mean 26 weeks and 3 days). The estimated time from fetal death to induction ranged from 1 day to 3 weeks (mean 8 days). Induction was successful in all cases with a mean induction to delivery time of 9 hours and 30 minutes. The mean dose of prostaglandin required was 0.914 gms and of oxotocin 12.78 I.U.s. Minor side effects were experienced by 16% of patients though none were serious. This series confirms the combination of extra-amniotic prostaglandin and intravenous oxytocin as an effective means of inducing labour where fetal death has occurred. PMID- 2094695 TI - Gallstone ileus following cholecystectomy and side to side choledochoduodenostomy. PMID- 2094696 TI - Mortality in the first year after coronary artery bypass surgery. Irish Cardiac Surgery Register. AB - In the three years 1983-1985 the Irish Cardiac Surgery Register (ICSR) recorded details on 1,534 patients who underwent primary isolated coronary artery bypass grafting (CABG). This unselected series of patients accounted for all such operations in the Republic of Ireland during this period and provides information on a wide spectrum of clinical subgroups of patients with ischaemic heart disease. There were 52 operative deaths (3.4%). At one year the number of deaths had risen to 75 (4.9%). Factors related to operative mortality were female sex, age greater than 60, left ventricular failure, history of myocardial infarction in the six weeks prior to surgery, poor left ventricular function and extensive disease of vessels to be grafted. All of the above factors except female sex were related to one year mortality. Analysis of late deaths (1.5%) separately showed evidence of pre-operative impaired left ventricular function to be an important prognostic indicator. PMID- 2094698 TI - High-performance liquid chromatographic determination of cilastatin and its major metabolite N-acetylcilastatin in rat plasma, urine and bile. AB - A new high-performance liquid chromatographic method coupled with solid-phase (C8) sample extraction has been developed for the simultaneous quantification of cilastatin and its major metabolite N-acetylcilastatin in rat plasma, urine and bile. The method is linear, reproducible and reliable with a detection limit of 1 microgram/ml in all three fluids. Plasma concentrations of cilastatin and N acetylcilastatin at selected time intervals and biliary and urinary recoveries of cilastatin and N-acetylcilastatin following an intravenous dose of 10 mg/kg cilastatin are presented. PMID- 2094697 TI - Improved fluorometric high-performance liquid chromatographic assay for (-) carbovir in rat blood and urine. AB - Carbovir is a carbocyclic guanosine analogue with potent in vitro activity against the human immunodeficiency virus. All of the activity resides in the (-) enantiomer. An ion-paired liquid chromatographic assay for (-)-carbovir was developed on a Spherisorb C8 column with fluorescence detection (275 nm excitation, 345 nm emission). Guanosine nucleosides are fluorescent at a pH less than 2.5, and fluorescence detection resulted in a four-fold improvement in the limit of quantitation (0.039 microgram/ml) compared to the previously developed assay with ultraviolet detection. Standard curves were processed with an internal standard at (-)-carbovir concentrations of 0.039-40 micrograms/ml in whole rat blood with a solid-phase extraction technique. Total variability was less than 16% at all concentrations and less than 10% at concentrations greater than 0.3 microgram/ml. Within-day variability was less than 7.5% at concentrations greater than 0.3 microgram/ml. Urine was analyzed directly after dilution and an diethyl ether wash to remove impurities. The total coefficients of variation were less than 10% from 0.5-20 micrograms/ml in urine. The concentrations of (-)-carbovir in rat blood were detectable for as long as 8 h after intravenous and oral doses of 20 and 60 mg/kg, respectively. PMID- 2094699 TI - Stereoselective analysis of fenoprofen and its metabolites. AB - Reversed-phase high-performance liquid chromatographic assays have been developed to quantitate simultaneously fenoprofen and its major metabolites as well as to distinguish between their R- and S- enantiomers following a single oral dose of 600 mg racemic fenoprofen to healthy volunteers. The compounds are extracted from plasma (after precipitation of plasma protein) or assayed directly in diluted urine samples employing a gradient solution on a C18 column and ultraviolet detection. Two internal standards, ketoprofen and flunoxaprofen, are used to allow measurement of very low (0.05 microgram/ml) and high (70 microgram/ml) concentrations in each sample. R- and S-fenoprofen glucuronides can be separated directly; the 4'-hydroxyfenoprofen conjugates are measured via an indirect method by comparing the concentration of 4'-hydroxyfenoprofen before and after hydrolysis. The R- and S-enantiomers of both parent and 4'-hydroxy metabolite are derivatized with L-leucinamide via an ethyl chloroformate intermediate and subsequently analyzed on a C18 column. Concentrations of metabolites found in plasma were low when compared to parent drug. The S/R ratio of fenoprofen in plasma always exceeds 1 and increases with time after dosage while the S/R ratio of its 4'-hydroxy metabolite remains almost unchanged at 1.1. R-Fenoprofen glucuronide disappears rapidly from plasma as compared to its S-antipode; a less pronounced difference is noted between R- and S-4'-hydroxyfenoprofen conjugates. Fenoprofen is almost completely excreted as its S-acyl glucuronides; the renal clearance of unchanged drug is very low. PMID- 2094700 TI - Optimization of conditions for the simultaneous separation of ten tryptophan metabolites using reversed-phase high-performance liquid chromatography. AB - A reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the separation of tryptophan and ten metabolites of tryptophan pyrrolase pathway has been developed by sequential optimization of mobile phase, by adjusting the pH, the concentration of triethylamine and the gradient elution. The baseline resolution of the compounds, by this optimized procedure, is obtained with an analysis time, including the re-equilibration period, of less than 30 min. We believe this is the first RP-HPLC method that can separate tryptophan and ten of its metabolites in a single chromatographic run. PMID- 2094701 TI - Determination of 4-amino-1-hydroxybutane-1,1-bisphosphonic acid in urine by automated pre-column derivatization with 2,3-naphthalene dicarboxyaldehyde and high-performance liquid chromatography with fluorescence detection. AB - A sensitive (5 ng/ml) method for the determination of 4-amino-1-hydroxybutane-1,1 bisphosphonic acid in human urine is described. The procedure includes (1) the isolation of the drug from urine by co-precipitation of its calcium salt with endogenous phosphates in the presence of base, (2) a solid-phase anion-exchange sample clean-up and (3) automated pre-column derivatization of the primary amino group with 2,3-naphthalene dicarboxyaldehyde-cyanide reagent followed by fluorescence detection of the N-substituted cyanobenz[f]isoindole derivative. The derivative of the drug was synthesized and its spectral and fluorescence properties were evaluated. The fluorescence quantum efficiency was determined to be 0.82 in the mobile phase used for the assay. The derivative is also capable of accepting energy in an oxalate ester-hydrogen peroxide chemiluminescence system. PMID- 2094702 TI - High-performance liquid chromatography of the antihistamine pyrilamine and its N oxide using electrochemical detection. AB - The electrochemical behavior of the over-the-counter antihistamine drug pyrilamine and its N-oxide analogue, have been studied by several voltammetric methods. Cyclic voltammograms of pyrilamine maleate in 0.1 M ammonium acetate at pH 7.0 indicated a quasi-reversible electrode process by observing a wave at + 0.85 V and + 1.30 V in the initial anodic sweep followed by a wave at - 1.30 V versus Ag/AgCl. Differential pulse and hydrodynamic voltammetry of pyrilamine and the N-oxide were examined to determine oxidation potentials for use in high performance liquid chromatography with electrochemical detection (HPLC-ED). Differentiation between pyrilamine and its N-oxide was achieved in HPLC-ED analyses at a detection potential of + 0.7 V and + 0.9 V versus Ag/AgCl with tandem ultraviolet detection at 254 nm. Utility of the HPLC-ED method was demonstrated by the analysis of pyrilamine and the N-oxide in microbial biotransformation samples. PMID- 2094703 TI - Determination of betaxolol and its metabolites in blood and urine by high performance liquid chromatography with fluorimetric detection. AB - Analytical methods for the determination of betaxolol and two of its metabolites in blood and urine are described. Betaxolol, alpha-hydroxybetaxolol, and the acid metabolite were extracted, with over 65% efficiency, from biological samples by liquid-liquid extraction methods. Analysis was performed using reversed-phase high-performance liquid chromatography with fluorimetric detection. N,N Dimethyloctylamine (0.005 M) was used to improve the chromatography of betaxolol and alpha-hydroxybetaxolol, while acetic acid (1%) was used for the acid metabolite. An excitation wavelength of 200 nm was found to produce the best detector response. Linear standard curves were obtained for all three compounds with detection limits (signal-to-noise ratio = 3) varying between 1 and 10 ng/ml. The coefficients of variation of the determination for all three compounds in blood and urine varied between 3.0 and 8.7%. The metabolism of betaxolol was studied in twelve healthy male subjects. The amounts (mean +/- S.D.) of betaxolol, alpha-hydroxybetaxolol and the acid metabolite renally excreted in the first 48 h after intravenous administration of 10 mg of betaxolol hydrochloride are 17.1 +/- 6.2, 0.4 +/- 0.1 and 14.5 +/- 3.7%, respectively, of the administered dose. PMID- 2094704 TI - Determination of zonisamide (3-sulphamoylmethyl-1,2-benzisoxazole) in plasma at therapeutic concentrations by high-performance liquid chromatography. AB - A selective and sensitive liquid chromatographic method for the determination of zonisamide in small (0.1 ml) plasma samples is described. After adding internal standard, a direct solvent extract of the sample is examined by reversed-phase liquid chromatography with ultra-violet spectrophotometric detection. The method is rapid, simple and capable of determining plasma levels after therapeutic ingestion of zonisamide. Some results from a dose-ranging clinical trial are presented. PMID- 2094705 TI - Gas chromatographic-mass spectrometric characterisation of unsaturated dicarboxylic acids in urine. PMID- 2094706 TI - High-performance liquid chromatographic determination of (Me)Arg-Lys-Pro-Trp tert.-Leu-Leu in plasma. PMID- 2094708 TI - High-performance liquid chromatographic method for the determination of 3 methylcholanthrene in channel catfish plasma. PMID- 2094707 TI - Gas chromatographic analysis of alprazolam in plasma: replicability, stability and specificity. PMID- 2094709 TI - High-performance liquid chromatography of sulfapyridine and its acetyl and glucuronide metabolites in rat and human urine. PMID- 2094710 TI - Quantitation of metolazone in urine by high-performance liquid chromatography with fluorescence detection. PMID- 2094712 TI - Determination of ornidazole and its main metabolites in biological fluids. PMID- 2094711 TI - Serum amino acid analysis with pre-column derivatization: comparison of the o phthaldialdehyde and N,N-diethyl-2,4-dinitro-5-fluoroaniline methods. AB - We compared two pre-column derivatization methods, o-phthaldialdehyde (OPA) and N,N-diethyl-2,4-dinitro-5-fluoroaniline (FDNDEA), for analysis of serum amino acids by reversed-phase high-performance liquid chromatography. Separations took 102 and 106 min for FDNDEA and OPA (reconditioning included), respectively, allowing a very good resolution of 30 amino acids by the former process and 38 by the latter. Linearity, within- and between-day variability and advantages in terms of accuracy and speed were studied for both methods. Twenty serum samples from healthy volunteers were assayed with OPA, FDNDEA and with the reference method of ion-exchange and post-column ninhydrin reaction (amino acid analyser), which took 170 min. The correlation between OPA and ninhydrin was good for all the amino acids (r = 0.959) except for the last-eluting lysine. Good agreement was found for FDNDEA (r = 0.987), which appeared in general to be a highly reproducible technique. Both pre-column methods were more sensitive than the post column ninhydrin method. PMID- 2094713 TI - Simultaneous determination of ketorolac and its hydroxylated metabolite in plasma by high-performance liquid chromatography. PMID- 2094714 TI - High-performance liquid chromatography of naftopidil, a novel antihypertensive drug, and two metabolites in human plasma. PMID- 2094715 TI - Sensitive detection and determination of cimetidine in human tissues with high performance liquid chromatography. PMID- 2094716 TI - Determination of the 5-lipoxygenase inhibitor (CGS 8515) in plasma by high performance liquid chromatography using reductive electrochemical detection. PMID- 2094717 TI - Measurement of 4-hydroxyanisole in serum by direct injection high-performance liquid chromatography. PMID- 2094718 TI - High-performance liquid chromatographic assay of sotalol: improved procedure and investigation of peak broadening. PMID- 2094719 TI - High-performance liquid chromatographic analysis of chlorambucil tert.-butyl ester and its active metabolites chlorambucil and phenylacetic mustard in plasma and tissue. PMID- 2094720 TI - Determination of psilocin in rat urine by high-performance liquid chromatography with electrochemical detection. PMID- 2094721 TI - Determination of pyridostigmine plasma concentrations by high-performance liquid chromatography. PMID- 2094722 TI - Insulin degradation in vivo: a high-performance liquid chromatographic analysis. AB - The metabolism of insulin in vivo was investigated using an isocratic reversed phase high-performance liquid chromatographic (RP-HPLC) method. After intravenous injection of A14-[125I]insulin into normals, eight labelled insulin derivatives were found in plasma (peaks 1-8). Two of them (peaks 1 and 7) showed an elution pattern identical with those of reference [125I]monoiodotyrosine and intact A14 [125I]insulin, respectively. Of the other six peaks, five (2-6) eluted before and one (peak 8) after insulin. This pattern was highly reproducible in terms of capacity factors and peak heights. Radioactivity separated by RP-HPLC was further characterized for its trichloroacetic acid precipitability and immunoprecipitability. Fractions corresponding to peaks 4-6 and 8, which showed an immunoprecipitability higher than 50%, were pooled in order to obtain sufficient radioactivity and were found to be insulin separated by Sephadex G-50 chromatography, containing in its structure, after sulphitolysis, intact A-chain and to be partially rebindable to monocyte insulin receptors. These data demonstrate that in blood, products of insulin metabolism circulate which retain a part of the immunological and biological properties of the hormone. These products are clearly separated from one another and from intact insulin by RP HPLC, suggesting that the appropriate use of this technique may allow a further and more accurate qualitative and quantitative characterization of in vivo insulin metabolism in physiological and pathological conditions. PMID- 2094723 TI - Two-dimensional polyacrylamide gel electrophoretic pattern of duodenal tumour proteins. AB - We investigated the protein pattern of a surgically resected tumour in a case where it was difficult to distinguish between duodenal and pancreatic cancer. The investigation was performed using two-dimensional polyacrylamide gel electrophoresis with silver staining. Samples of the duodenal tumour, normal duodenal mucosa and normal pancreatic tissue from the same patient were compared. Each gel had ca. 250-300 protein spots, and the tumour sample pattern more closely resembled that of normal duodenal mucosa than that of pancreatic tissue, suggesting that the tumour had arisen from duodenal mucosa. There were three proteins identified only in the tumour sample gel, and these may have been tumour specific proteins. PMID- 2094724 TI - Direct determination of styrene-7,8-oxide in blood by gas chromatography with flame ionization detection. AB - A simple capillary gas chromatographic method is described for direct determination of styrene-7,8-oxide (styrene oxide) in blood samples of 1 ml, with a detection limit of 1 ng/ml. After the addition of 1-phenylpropylene oxide as internal standard, blood samples were extracted with n-hexane, the n-hexane phases were concentrated under nitrogen, and up to 25 microliters of the resulting solution were injected on-column using a retention gap. Separation was carried out on a fused-silica capillary column coupled to a flame ionization detector. Using this method the metabolism of styrene oxide in rat blood was investigated. Concentrations of styrene oxide in the blood of rats exposed to styrene at atmospheric concentrations between 20 and 800 ppm for 3 h at steady state conditions are reported. PMID- 2094725 TI - Simultaneous high-performance liquid chromatographic analysis of carbidopa, levodopa and 3-O-methyldopa in plasma and carbidopa, levodopa and dopamine in urine using electrochemical detection. AB - Two assay procedures are described for the analysis of levodopa, carbidopa and 3 O-methyldopa in plasma and levodopa, carbidopa and dopamine in urine. The methods are suitable for quantifying the analytes following therapeutic administration of levodopa and carbidopa. Both were based on reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection and with methyldopa as the internal standard. Plasma samples were prepared by perchloric acid precipitation followed by the direct injection of the supernatant. Urine was prepared by alumina adsorption, and the analytes were desorbed with perchloric acid solution containing disodium EDTA and sodium metabisulfite prior to injection into the HPLC system. The methods have been utilized to evaluate the pharmacokinetics and bioavailability of oral dosage forms containing levodopa and carbidopa. PMID- 2094726 TI - Comparison of shear bond strengths of orthodontic resins to ceramic and metal brackets. PMID- 2094727 TI - Sliding tube appliance for maxillary canine retraction. PMID- 2094728 TI - The readers' corner. PMID- 2094729 TI - Differences in anterior retraction between identical twins. PMID- 2094730 TI - Patient appreciation: the cornerstone of internal marketing. PMID- 2094731 TI - Results of JCO issues survey. PMID- 2094733 TI - Occlusal splint for patient with severe gagging behavior. PMID- 2094732 TI - Permanent lingual bonded retainer. PMID- 2094734 TI - Computer evolution = management revolution. PMID- 2094735 TI - Saving impacted teeth. PMID- 2094736 TI - Controlled space closure with a preadjusted appliance system. PMID- 2094737 TI - The communicative function hypothesis: an operant behavior perspective. AB - The suggestion that all problem behaviors may serve a communicative function is explored from an operant perspective. An analysis of the environmental functions of operant behavior involves an understanding of two sets of relations: (1) two types of reinforcement contingencies (positive and negative) and (2) two types of operant behaviors (verbal and non-verbal). Such an operant analysis reveals that not all problem behaviors may currently serve a communicative function. However, often an alternate replacement behavior can be developed that would achieve the same environmental effect as the problem behavior through social mediation and thereby be communicative in nature. A theoretical classification system for identifying the type of function a problem behavior may serve is advanced. Implications for prescribing behavioral treatments based on this model are presented. PMID- 2094738 TI - Operant self-control procedure in modifying Type A behavior. AB - A multiple-baseline across subjects design was used to evaluate the effects of operant self-control procedure on altering speed/impatient behaviors of the Type A behavior pattern (TABP). The operant-self-control procedure consisted of self monitoring, self-evaluation, and self-reinforcement. The results demonstrated empirically significant decreases in S/I behaviors of the TABP following transfer to the self-reinforcement condition. Significant reductions in the Jenkins Activity Survey and physical symptoms scores additionally evidenced the effects of the operant self-control procedure. The possibility of pathogenic factors of the TABP varying with culture, and the advantages of the operant self-control procedure are discussed. PMID- 2094739 TI - Virtue rewarded: reinforcement and punishment in an acute psychiatric admission ward. AB - This study evaluated the naturally occurring behaviour of psychiatric patients in an acute psychiatric setting. Direct behavioural observations were carried out to determine the amount of time patients spent in interaction, with whom they interacted, and the nature of the interaction. Also examined were each respondent group's type and rate of interactive behavior. For much of the time no interactive behaviour was observed to occur, but much of the behaviour exhibited by patients was socially appropriate. When social interactions did occur, both fellow patients and staff tended to reinforce appropriate behaviour. However, nurses reinforced inappropriate crazy behaviour much less than did fellow patients or non-nursing staff. Treatment implications are discussed. PMID- 2094740 TI - Improving dietary habits of children: effects of nutrition education and correspondence training. AB - Evidence that a significant number of children are exposed to risk factors associated with coronary heart disease has prompted health care professionals to develop programs designed to encourage the early development of a healthy life style. The present study used a multiple baseline approach to examine the effects of two procedures on the snack selection behavior of 25 third grade children. In children who selected non-nutritious rather than nutritious snacks for more than 40% of the baseline observations, nutrition education alone had little or no impact on their selection of snacks. However, with the implementation of correspondence training, in which a reward was made contingent upon carrying out a stated intent to choose a nutritious snack, the children consistently chose nutritious snacks. These results indicate that correspondence training may be an efficient and cost-effective way to improve dietary habits of young people. PMID- 2094742 TI - The treatment of elopement behavior in a retardate using a graduated levels program. AB - The present study investigated whether a levels program would effectively reduce the amount of elopement (running-away) behavior demonstrated by an adult with profound mental retardation. The subject resided in an Alternative Intermediate Services (AIS) group home. During baseline data collection, he demonstrated an average of 131 elopements per month. After implementation of the levels program, elopements decreased to 0 within 7 months. At the end of the study, the subject's elopements continued to be maintained at a very low rate. PMID- 2094741 TI - The use of covert sensitization and social skills training in the treatment of an obscene telephone caller. AB - This case study examines the use of covert sensitization and social skills training to treat an obscene telephone caller on a behaviorally-oriented inpatient psychiatric unit. Rapid decreases in penile tumescence associated with obscene telephone calling were obtained after covert sensitization treatment and were maintained at one year follow-up. Social skills training led to a decrease in social anxiety and increase in social behavior. Results support the combined clinical effectiveness of covert sensitization and social skills training for the treatment of obscene telephone calling. PMID- 2094743 TI - Subclass characteristics of IgG autoantibodies in bullous pemphigoid and pemphigus. AB - Immunoglobulin (Ig) G subclasses in anti-basement membrane zone (BMZ) autoantibodies found in the sera of bullous pemphigoid (BP) and in anti intercellular substance (ICS) autoantibodies of pemphigus were investigated using immunofluorescent (IF) staining. In BP, IgG4, IgG1, and IgG2 were detected in 13, 5 and 6 of 15 patients, respectively; IgG3 was not detected. In pemphigus, IgG4 was detected in all of 10 patients, IgG1 in 7, IgG2 in one, and IgG3 in one patient, respectively. In both BP and pemphigus, the most prominent subclass in intensity of IF staining was IgG4. Although one BP and one PV patient had only IgG4 autoantibodies, C3 deposition was detected. The quantification of IgG subclasses in the sera of the patients was performed by enzyme-linked immunosorbent assays (ELISA). Serum levels of IgG4 in both BP and pemphigus were elevated approximately 3-fold over those in normal controls; those of whole IgG and IgG1-3 were not significantly elevated. Using direct IF staining, the deposition of C3 at the BMZ and at the ICS was demonstrated in 9 of 10 BP and in 3 of 8 pemphigus patients, respectively. The prominent IgG subclasses of anti-BMZ and anti-ICS antibody were IgG4, a noncomplement-fixing antibody, suggesting that the deposition of C3 in the lesional skin occurred via the alternative pathway, or that small amounts of IgG1-3 subclass autoantibodies activated the classical pathway. PMID- 2094745 TI - Anticonvulsant syndrome with multiple symptoms, including porphyria, IgA deficiency, and liver dysfunction. AB - A 19-year-old Japanese female who had been treated for epilepsy with a combined phenytoin-phenobarbital preparation for the past three years presented with increasing skin pigmentation and hirsutism. She had suffered two attacks of loss of consciousness after bilateral partial oophorectomy at the age of 16. Investigations revealed a marked increase in coproporphyrin levels in the urine and feces, a marked decrease in her serum IgA level, and liver dysfunction. All these manifestations gradually improved upon the withdrawal of her antiepileptic treatment. In vitro studies revealed B cell dysfunction producing IgA deficiency, which normalized within one year after discontinuation of the antiepileptic therapy. It was assumed that her treatment had worsened preexisting porphyria, which was misdiagnosed as epilepsy because of abnormal EEG findings. The type of porphyria appeared to be hereditary coproporphyria, despite the lack of a family history. PMID- 2094744 TI - Co-culture of human hair follicles and dermal papillae in a collagen matrix. AB - Human hair follicles, either alone or in combination with dermal papillae, were cultured in a collagen matrix. When plucked hair follicles were cultured alone, spike-like structures composed of outer root sheath cells started growing around the follicle and then radiated into the gel. When isolated dermal papillae were embedded close to the follicles, spikes started growing earlier and grew more rapidly than without the papillae. In cultures of excised follicles from which the dermal papilla had been removed, epithelial cells (possibly hair bulb cells) started growing out from the bulbous portion and then also formed spikes. In the presence of a papilla, the spikes elongated toward the papilla, finally reaching and surrounding it. These findings suggest that dermal papilla cells produce a factor(s) that enhances growth of follicular epithelial cells and also attracts those cells. In cultures of whole excised follicles, two major characteristic patterns of cellular growth were recognized. When the dermal papilla remained inside the bulb in contact with the hair bulb matrix, the hair matrix cells proliferated and differentiated in the normal manner, resulting in elongation of the hair shaft and follicle. But when the papilla was detached from the hair bulb matrix, epithelial cells proliferated from the bulbous portion and finally formed hair follicle-like structures. Thus, attachment of the dermal papilla to the hair bulb matrix in the bulbous portion appears to be necessary for growth of the hair and follicle in the normal manner. Our model may be useful for examining the interaction between follicular epithelial cells and dermal papillae and for studying the growth of hair and follicles in vitro. PMID- 2094746 TI - Epidermolysis bullosa atrophicans generalisata mitis--report of a case with renal dysfunction. AB - A male adult epidermolysis bullosa atrophicans generalisata mitis (EBAGM) patient with renal dysfunction is described. The abnormal urological findings were improved together and healing of the generalized skin erosions occurred. To our best knowledge, he is the 3rd EBAGM patient with urological abnormalities in the world. PMID- 2094747 TI - Hair follicle nevus with hyperplasia of smooth and striated muscle. AB - We report a peculiar nevus which occurred on the left side of the chin of an 18 year-old male. It had been present for four years and had grown rapidly during the last year. Histologically, many hair follicles, smooth muscles, and striated muscles were found within the reticular dermis. The hair follicles were accompanied by mature sebaceous glands; numerous eccrine glands were seen in the middle and deep dermis. Immunohistochemical stain and phosphotungstic acid hematoxylin stain supported the fact that the muscles seen between the follicles were both smooth and striated. This nevus was considered to be a hair follicle nevus accompanied by hyperplasia of smooth muscles and striated muscles. PMID- 2094748 TI - Hemangiopericytoma: characteristic features observed by magnetic resonance imaging and angiography. AB - Hemangiopericytoma is a rare vascular tumor which may originate wherever there are capillaries. We report a case of this tumor occurring in a 79-year-old Japanese man, which originated from the subcutaneous tissues of the left upper arm and reached a size of 6 x 5 x 4 cm. Histopathological and electron microscopical findings were compatible with those of benign-type hemangiopericytoma. Magnetic resonance imaging showed the most intense signal on proton density images. Angiography showed the characteristic tumor feeder artery forming a pedicle which entered the tumor and branched radially and a dense, uniform, well-demarcated, oval tumor stain. These images were helpful in performing proper operative treatment without noteworthy bleeding. These modern modalities are excellent non-invasive treatment without diagnostic procedures for the vascular tumors of soft tissues in dermatology. PMID- 2094749 TI - 1 alpha,24R-dihydroxyvitamin D3 has an ability comparable to that of 1 alpha,25 dihydroxyvitamin D3 to induce keratinocyte differentiation. AB - Using cultured normal human keratinocytes, we compared the activities of 1 alpha,24-dihydroxyvitamin D3 (1,25(OH)2D3), a biologically active form, in inducing cell differentiation. Treatment with 10(-6) M of 1,24R(OH)2D3 and 1,25(OH)2D3 increased the number of involucrin positive cells (differentiated from 6.4% to 24.1% and 25.1%, respectively. These results indicate that 1,24R(OH)2D3 has an ability comparable to that of 1,25(OH)2D3 to induce cell differentiation in human keratinocytes. The clinical effectiveness of 1,24R(OH)2D3 for the treatment of psoriasis may be, in part, related to its direct effect on hyperproliferative keratinocytes. PMID- 2094751 TI - An evaluation of the selection process of hospital information systems. AB - This research study evaluates the selection process of a Hospital Information System (HIS), focusing on the level of compromise required by healthcare professionals during said process and the level of satisfaction achieved with the system selected. How other variables, such as job title, length of experience in the healthcare, data processing, and information systems fields affect these measured levels are also evaluated. Results of this study indicate that a HIS is critical to the viability of a hospital's operation and the level of compromises made during the selection process have an impact upon the how satisfied the healthcare provider is with the HIS they select. PMID- 2094750 TI - A computer workstation for clinical medicine. AB - New computer tools for physicians, nurses, and the medical care team will become common in the 1990s. This paper describes a clinical workstation (CWS) development project that uses new technology that moves the technical support for medical decision making from the computer room to the nursing station. Collection, processing, and display of clinical information including patient identification, laboratory, and radiology results and current medications are carried out in the environment of a multi-windowed computer workstation. Easy access to automated medical literature databases from the workstation is also provided. This pilot project has successfully demonstrated a CWS operating on an acute general neurology and neurosurgical inpatient nursing unit and a critical care unit at The Johns Hopkins Hospital. PMID- 2094752 TI - Medical care classification systems in the ambulatory care environment: an evaluative framework. AB - An essential need of a Quality Assurance Program (QAP) in an ambulatory care setting is accurate and reliable information characterizing the encounter between patient and provider. This information includes identification of the patient's reason for visit, the provider's diagnostic impressions, and procedures performed. Such data can be used to maintain an informational index on the nature of patient care. Based upon this index, a wide variety of special studies in the assessment and assurance of the quality of care can be conducted. A primary consideration in the development of such an index is the choice of a Medical Care Classification System (MCCS) to be used to code encounter-related data. The objective of this paper is to provide a methodology and evaluative framework in which available Medical Care Classification Systems can be assessed as to which one best meets the needs of the quality assurance programs within ambulatory care settings. PMID- 2094753 TI - "NEONATE"--an expert application for the "HELP" system: comparison of the computer's and the physician's problem list. AB - NEONATE is a prototype of an expert application for the HELP Hospital Information System. Its goal is to improve documentation in the Newborn Intensive Care Unit. The decision module of NEONATE is designed to produce an admission problem list. In this paper, the admission problem list that NEONATE generates was compared to the admission problem list of the current CETUS system for 30 patients. These were compared to a retrospectively constructed gold standard problem list. Of 101 problems in the gold standard list, 56 were on the current admission reports; 82 were found by NEONATE. NEONATE found 31 problems missed on the current admission reports; the current admission reports contained 5 problems missed by NEONATE. The current admission reports contained 9 false positives; whereas NEONATE's reports contained 27. Of the 27, 16 were caused by a single rule in NEONATE. We conclude that an expert system has great potential for improving the documentation of the patient problem list. PMID- 2094754 TI - Measuring technical efficiency in health care organizations. AB - The rising cost of health care has created great interest in developing methods to increase the efficiency of health care organizations. Despite this interest most analyses of prospective payment and other programs designed to control expenditures have examined costs and not efficiency. This article examines a new technique--data envelopment analysis (DEA)--that facilitates the conduct of efficiency studies. The utility of DEA is analyzed by comparing this technique with other methods used to measure efficiency, by discussing the application of DEA in the health care industry and by assessing the validity of results from DEA studies. The article concludes with an assessment of the strengths and weaknesses of DEA and suggestions for refining this technique. PMID- 2094755 TI - Electron microscopic studies of medullary synaptic inputs to vasopressin containing neurons in the hypothalamic paraventricular nucleus. AB - We have observed the ascending projections from the lower brain stem to the magnocellular vasopressin-like immunoreactive (VP-LI) neurosecretory neurons in the paraventricular nucleus (PVN) using electron microscopy. The tissues were prepared by a double labeling technique combining anterograde tracing after iontophoretic injection of wheat germ agglutinin-coupled horseradish peroxidase (WGA-HRP) in the A1 group (lateral reticular nucleus in the medulla oblongata) with VP immunocytochemistry. Both the WGA-HRP-labeled and the unlabeled axon terminals made synaptic contacts with VP-LI cell bodies and processes in the PVN. This indicates a direct synaptic influence of medullary A1 group on the secretory activity of the VP-containing neurons in the hypothalamic paraventricular nucleus. PMID- 2094756 TI - Correlative light microscopy, scanning electron microscopy, and transmission electron microscopy of osmium-macerated biological tissues. AB - A method facilitating correlation of light microscopic (LM), scanning electron microscopic (SEM) and transmission electron microscopic (TEM) images was developed. Rat kidney and heart were initially subjected to the osmium maceration procedure and then embedded in acrylic resin. Semithin sections of the tissue blocks were first provided for LM and then examined by SEM after resin removal. Furthermore, the ultrathin sections adjacent to the semithin sections were observed by TEM. The three-dimensional images of intracellular organelles provided an informative adjunct to LM and TEM. PMID- 2094757 TI - Comparison of the Canal Master endodontic instrument and K-type files for enlargement of curved root canals. AB - Twenty mandibular molars with 40 mesial curved root canals were instrumented with a circumferential technique using K files and the Canal Master instrumentation technique by junior dental students whose only endodontic experience had been completion of a preclinical endodontic course. Preoperative and postoperative radiographs were taken facially and mesially with instruments in place. The canals were evaluated radiographically for transportation 1 mm and 4 mm from the apex. The mesial roots were cross-sectioned at the same level. The sections were evaluated for roundness of the canal preparation. It was concluded that the Canal Master instrumentation technique transported the root canal less and produced rounder preparations than the K file circumferential technique. There appears to be a greater tendency for breakage with the Canal Master. PMID- 2094758 TI - In vitro bacterial penetration of coronally unsealed endodontically treated teeth. AB - Forty-five root canals were cleaned, shaped, and then obturated with gutta-percha and root canal sealer, using a lateral condensation technique. The coronal portions of the root filling materials were placed in contact with Staphylococcus epidermidis and Proteus vulgaris. The number of days required for these bacteria to penetrate the entire root canals was determined. Over 50% of the root canals were completely contaminated after 19-day exposure to S. epidermidis. Fifty percent of the root canals were also totally contaminated when the coronal surfaces of their fillings were exposed to P. vulgaris for 42 days. PMID- 2094759 TI - Cervical root resorption following bleaching of endodontically treated teeth. AB - One year following root canal treatment and internal etching and bleaching of anterior teeth in dogs, the animals were sacrificed and the teeth prepared for stereomicroscopic or light microscopic examination. Evidence of cervical root resorption and ankylosis was noted on several teeth. The bleaching factors associated with the teeth exhibiting resorption were heat with 30% hydrogen peroxide. Resorption was not related to walking bleach or to internal etching alone. PMID- 2094760 TI - Machining efficiency of Flex-R, K-Flex, Trio-Cut, and S Files. AB - Many root canal instruments with several different designs have been introduced during recent years. This article evaluates the machining properties of four such instruments: the Flex-R, K-Flex, Trio-Cut, and S file. There are large variations in the machining properties of these instruments. The results are comparable to findings when evaluating conventional root canal files which show that the Hedstrom file is much more efficient when considering removal of material than the K file. The Flex-R file, K-Flex file, and Trio-Cut file are similar in design. The two former brands perform in a similar fashion, while the Trio-Cut file is less efficient than any of the evaluated K files. The S file performs as a Hedstrom file which can be expected from its similarity in design to that instrument. PMID- 2094761 TI - Intraradicular bacteria and fungi in root-filled, asymptomatic human teeth with therapy-resistant periapical lesions: a long-term light and electron microscopic follow-up study. AB - Light and electron microscopy were used to analyze nine therapy-resistant and asymptomatic human periapical lesions, which were removed as block biopsies during surgical treatment of the affected teeth. The cases that required surgery represented about 10% of all of the cases which received endodontic treatment and root fillings during the period 1977 to 1984. These cases revealed periapical lesions when they were examined 4 to 10 yr after treatment. The biopsies were processed for correlated light and electron microscopy. Six of the nine biopsies revealed the presence of microorganisms in the apical root canal. Four contained one or more species of bacteria and two revealed yeasts. Of the four cases in which bacteria were found, only in one biopsy could they be found by light microscope. In the other three specimens, the bacterial presence could be confirmed only after repeated electron microscopic examination of the apical root canal by serial step-cutting technique. Among the three cases in which no microorganisms could be encountered, one showed histopathological features of a foreign body giant cell granuloma. These findings suggest that in the majority of root-filled human teeth with therapy-resistant periapical lesions, microorganisms may persist and may play a significant role in endodontic treatment failures. In certain instances such lesions may also be sustained by foreign body giant cell type of tissue responses at the periapex of root-filled teeth. PMID- 2094762 TI - Therapy-resistant foreign body giant cell granuloma at the periapex of a root filled human tooth. AB - Although the primary etiological factor of periapical lesions is microbial, there are other independent factors that can adversely affect the outcome of endodontic treatment. In this communication, we present morphological evidence in support of the role of a foreign body reaction of periapical tissue to root-filling materials. The specimen consisted of a surgical biopsy of an asymptomatic periapical lesion which persisted after a decade of postendodontic follow-up. The biopsy was processed for correlated light and electron microscopy and was analyzed by various microtechniques. The unique feature of the lesion was the presence of vast numbers of large multinucleated cells and their cytoplasmic inclusion bodies. Morphologically, these multinucleated cells resembled foreign body giant cells. They contained characteristic birefringent cytoplasmic inclusions which on electron-probe X-ray microanalysis consistently revealed the presence of magnesium and silicon. The magnesium and silicon are presumably the remnants of a root-filling excess which protruded into the periapex and had been resorbed during the follow-up period. These observations strongly suggest that in the absence of microbial factors, root-filling materials which contain irritating substances can evoke a foreign body reaction at the periapex, leading to the development of asymptomatic periapical lesions that may remain refractory to endodontic therapy for long periods of time. PMID- 2094763 TI - Removal of silver cones and fractured instruments using the Canal Finder System. AB - Removal of fractured instruments and silver cones was undertaken experimentally and clinically using the automated Canal Finder System. In all cases manual retrieval had been tried and had failed. Fifteen of 50 fragments could be removed completely and 11 fragments could be bypassed using the Canal Finder System. In 24 teeth the use of the Canal Finder was not successful, in 7 teeth the root canal was perforated or the fragment was pushed through the apical foramen. Removal of silver cones was undertaken in 38 root canals with 40 cones. Eighteen of them could be removed using the Canal Finder. Two cones could be bypassed only. Eight of the remaining 20 cones which could not be removed initially, finally could be removed after combined use of the Canal Finder and an ultrasonic device. The results of this study indicate that the Canal Finder System may be used as an auxillary device in difficult cases of removal of silver cones and fractured instruments. PMID- 2094764 TI - Bilateral C shape configuration in maxillary first molars. AB - The C-shaped canal is unusual. It is most frequently reported in mandibular molars. A case of bilateral C-shaped canals in maxillary molars is reported here. PMID- 2094765 TI - Adjuncts to posterior endodontic surgery. AB - Adjuncts to posterior endodontic surgery include fiberoptics, high-torque handpieces, and optical magnification. These current technologies allow the clinician to expand and amplify his surgical techniques. The patient can now have the benefit of treatment options not available previously. PMID- 2094766 TI - The mechanism of inhibition of S-adenosyl-L-homocysteine hydrolase by fluorine containing adenosine analogs. AB - (Z)-4',5'-Didehydro-5'-deoxy-5'-fluoroadenosine (I), 5'-deoxy-5' difluoroadenosine (II), and 4',5'-didehydro-5'-deoxy-5'-fluoroarabinosyl adenosine (III) are inhibitors of rat liver S-adenosyl-L-homocysteine hydrolase. Compounds I and II are time-dependent and irreversible inhibitors of the enzyme. Both I and II are oxidized by E.NAD to produce E.NADH, and fluoride anion is formed in the inactivation reaction (0.7 to 1.0 mole fluoride/mole of enzyme subunit, and 1.7 moles fluoride/mole of enzyme subunit from I and II, respectively). The enzyme is stoichiometrically labeled with [8-3H]-I, but the label is lost upon denaturation of the protein either with or without treatment of the labeled complex with sodium borohydride. The compound III, the arabino derivative of I, is a competitive inhibitor of the enzyme. The mechanism of the inhibition of S-adenosyl-L-homocysteine hydrolase by these inhibitors is discussed. PMID- 2094767 TI - pH-dependent inhibitory effects of tris and lithium ion on intestinal brush border sucrase. AB - Tris and two of its hydroxylated amine analogs were examined in a metal-free, universal n-butylamine buffer, for their interaction with intestinal brush border sucrase. Our recent three-proton-families model (Vasseur, van Melle, Frangne and Alvarado (1988) Biochem. J., 251, 667-675) has provided the sucrase pK values necessary to interpret the present work. At pH 5.2, 2-amino-2-methyl-l-propanol (PM) causes activation whereas Tris has a concentration-dependent biphasic effect, first causing activation, then fully competitive inhibition. The amine species causing activation is the protonated, cationic form. The difference between the two amines is related to the fact that Tris has a much lower pKa value than PM (respectively, 8.2 and 9.8). Even at pH 5.2, Tris (but not PM) exists as a significant proportion of the free base which, by inhibiting the enzyme fully competitively, overshadows the activating effect of the cationic, protonated amine. Above pH 6.8, both Tris and PM act as fully competitive inhibitors. These inhibitions increase monotonically between pH 6.5 and 8.0 but, above pH 8, inhibition by 2.5 mM Tris tends to diminish whereas inhibition by 40 mM PM increases abruptly to be essentially complete at pH 9.3 and above. As pH increases from 7.6 to 9.0, the apparent affinity of the free amine bases decreases whereas that of the cationic, protonated amines, increases. In this way, the protonated amines replace their corresponding free bases as the most potent inhibitors at high pH. The pH-dependent inhibition by 300 mM Li+ is essentially complete at pH 8, independent of the presence or absence of either 2.5 mM Tris or 40 mM PM. Even at pH 7.6, an excess (300 mM) of Li+ causes significant increases in the apparent Ki value of each Tris, PD (2-amino-2-methyl 1-3-propanediol) and PM, suggesting the possibility of a relation between the effects of Li+ and those of the hydroxylated amines which in fact are mutually exclusive inhibitors. The inhibitory results are interpreted in terms of a mechanistic model in which the free bases bind at two distinct sites in the enzyme's active center. Binding at the glucosyl sub-site occurs through the amine's free hydroxyl groups. This positioning facilitates the interaction between the lone electron pair of the deprotonated amino group with a proton donor in the enzyme's active center, characterized by a pK0 around 8.1. When this same group deprotonates, then the protonated amines acting as proton donors replace the free bases as the species giving fully competitive inhibition of sucrase. PMID- 2094768 TI - Diethylbarbiturate potentiation of 2,4,6-trinitrobenzenesulphonate-induced rhodanese inactivation. AB - The rate of rhodanese inactivation by 2,4,6-trinitrobenzenesulphonate is increased in the presence of diethylbarbiturate in the reaction medium. A "rate saturation effect" indicates the formation of a rhodanese-diethylbarbiturate complex, prior to modification-induced enzyme inactivation. The dissociation constant of this complex is 19.0 mM. Diethylbarbiturate has no effect on the trinitrophenylation rate of the free amino groups of rhodanese. When rhodanese modification, in the presence of diethylbarbiturate in the reaction medium, is carried out by the use of a 2,4,6-trinitrobenzenesulphonate concentration much lower than the concentration of rhodanese modifiable amino groups, reaction stoichiometry indicates that 3 to 5 moles of rhodanese are rendered inactive for each mole of 2,4,6-trinitrobenzenesulphonate utilized. This finding indicates the existence of a chain-reaction type mechanism of rhodanese inactivation. PMID- 2094769 TI - Peptide diazomethyl ketones are inhibitors of subtilisin-type serine proteases. AB - Peptide diazomethyl ketones, well known as specific cysteine protease inhibitors are also potent inhibitors of the microbial serine proteases thermitase (EC 3.4.21.14) and subtilisin Carlsberg (EC 3.4.21.14). The affinity of the enzymes towards the synthetic inhibitors Z-Ala(n)-PheCHN2 (n = 0, 1, 2) depends on the chain length and is in the same range as for the corresponding chloromethyl ketones. Both kinds of inhibitors react irreversibly in a 1:1 ratio with the enzymes and covalently bind to the active site histidine of both subtilisin Carlsberg and thermitase despite the fact that thermitase contains an active-site cysteinyl residue. The mechanism of the inhibition reaction is discussed. PMID- 2094771 TI - Interpretation of biphasic protein modification and modification-induced enzyme inactivation reaction plots. PMID- 2094770 TI - Binding of the bovine basic pancreatic trypsin inhibitor (Kunitz) to the 33,000 Mr and 54,000 Mr species of human urokinase: thermodynamic study. AB - The effect of pH and temperature on the apparent association equilibrium constant (Ka) for the binding of the bovine basic pancreatic trypsin inhibitor (BPTI, Kunitz inhibitor) to the 33,000 Mr and 54,000 Mr species of human urokinase (EC 3.4.21.31) has been investigated. Under all the experimental conditions, values of Ka for BPTI binding to the 33,000 Mr and 54,000 Mr species of human urokinase are identical. On lowering the pH from 9.5 to 4.5, values of Ka (at 21.0 degrees C) for BPTI binding to human urokinase (33,000 Mr and 54,000 Mr species) decrease thus reflecting the acidic pK-shift of the His-57 catalytic residue from 6.9, in the free enzyme, to 5.1, in the proteinase:inhibitor complex. At pH 8.0, values of the apparent thermodynamic parameters for BPTI binding to human urokinase (33,000 Mr and 54,000 Mr species) are: Ka = 4.9 x 10(4) M-1, delta G degree = 6.3 kcal/mol, and delta S degree = -37 entropy units (all at 21.0 degrees C); and delta H degree = +4.6 kcal/mol (temperature independent over the explored range, from 5.0 degrees C to 45.0 degrees C). Thermodynamics of BPTI binding to human urokinase (33,000 Mr and 54,000 Mr species) have been analyzed in parallel with those of related serine (pro)enzyme Kazal- and /Kunitz-type inhibitor systems. Considering the known molecular models, the observed binding behaviour of BPTI to human urokinase (33,000 Mr and 54,000 Mr species) was related to the inferred stereochemistry of the proteinase/inhibitor contact region. PMID- 2094772 TI - Competitive inhibition of a tumour cell surface protease. A rapid technique for in vitro testing of selective targeting systems. AB - The active centre of a protease on the surface of tumour cells can be located by its affinity for an active site-directed inhibitor, 9-amino acridine. Cells which have uninhibited proteases, bind 9-amino acridine and fluoresce in resin sections. The leukaemic rat was used as a model system to provide tumour cells in a well defined location. Drugs when coupled to a ligand (directed to the active centre of the protease) compete for this binding site with 9-amino acridine. Thus, competitive inhibition of the tumour cell surface protease provides a rapid technique for demonstrating the delivery of liganded molecules to the surface of tumour cells in vitro. PMID- 2094773 TI - Stimulation of IFN-alpha production in HLA-DR+, light density peripheral blood mononuclear cells by human immunodeficiency virus. PMID- 2094774 TI - Jack fruit lectin binding pattern in carcinoma of the uterine cervix. AB - A lectin was isolated and purified from the seeds of Jack Fruit (Artocarpus integrifolia) using a column of immobilized N-acetyl D-Galactosamine. The Jack Fruit lectin (JFL) was conjugated to horse radish peroxidase (HRP). The purified conjugate was used to study the binding properties of tissues from carcinomas of the uterine cervix. The binding to cancer tissues was compared with that of normal controls. The carcinomatous cells showed varying degrees of binding towards JFL in contrast to normal controls which generally had uniform binding. The nature and intensity of binding of the lectin with the cancer tissues suggest that this lectin may be used as a diagnostic marker in carcinoma of uterine cervix. PMID- 2094775 TI - Effects of proteolytic enzymes on mammary tumor growth: in vitro and in vivo suppression and cellular death of tumor cells. AB - Proteolytic enzymes may have potential value in the prophylaxis of malignant tumor development. C3H/HEJ mice, used for their ability to produce spontaneous mammary tumors, were injected intraperitoneally (IP) with proteolytic enzyme hydrolysate at a dosage range of 0.038 to 0.462 mg/gm body weight. The injections were given every other day, once a day for six months. The pathology results showed suppression of growth, and necrosis (and in some cases encapsulation) of the mammary tumors in C3H/HEJ mice. Concurrently, SP 2/0-AG 14 cells grown in the presence of 0.25 mg enzyme/ml to 3.75 mg enzyme/ml of proteolytic enzymes, showed little cellular deterioration when the dosage range remained below 1 mg enzyme/ml. When dosage ranges were greater than 1 mg enzyme/ml, cellular necrosis occurred within three days of the addition of the proteolytic enzymes. These results demonstrate that the proteolytic enzymes used in these experiments were beneficial in preventing tumor development and prolonging survival of C3H/HEJ mice when used in the appropriate concentration range. A portion of these results were presented elsewhere (2nd Int. Biotechnol. Expo; Oct. 1989; San Francisco). PMID- 2094776 TI - Over 80% of NotI sites are associated with CpG rich islands in the sequenced human DNA. AB - Clones containing DNA segments linked to NotI sites are not only useful for ordering the NotI fragments fractionated by pulsed field gel, but also valuable in the search of unknown genes, because they often contain the CpG rich islands and genes related with them. To know the probability of association of NotI sites with CpG rich islands, we screened 5,188 sequences accumulated in DNA data base for the presence of NotI site and examined the distribution of CpGs around them. The sequential calculation of G + C content and frequency of CpG occurrence at each nucleotide position identified the CpG rich domains close to NotI sites in 77 sequences, which corresponds to 84% of total number of candidate sequences. This frequency is consistent well with the prediction that 89% of NotI sites in mammalian genome are likely to be present in CpG rich islands and would stress the importance of cloning of NotI linking sequences for direct isolation of desired genes. Furthermore, 63 islands newly identified in this study should provide a clue for understanding the transcriptional regulation of associated genes. PMID- 2094777 TI - Isoelectric focusing studies in Brazilian Indians--uncovering variation of ORM, AHSG and IF. AB - Allele frequencies for the orosomucoid 1 (ORM1), orosomucoid 2 (ORM2), alpha-2-HS glycoprotein (AHSG) and complement component I (IF) loci were studied in 393 individuals of three Brazilian Indian tribes. In the ORM1 locus only two alleles were observed among the Urubu-Kaapor, while five were found among the Pacaas Novos. The frequency of ORM1*1 was similar in these two tribes (0.734 and 0.715, respectively) but departed more markedly among the Parakana (0.870). Variation for ORM2 locus was found among the Pacaas Novos only, with ORM2*3 being observed in just three individuals. A new variant (AHSG*PN) was found in the AHSG system. Frequency for AHSG*1 was unexpectedly low in the three tribes, especially, among the Pacaas Novos, where the prevalence (0.145) is the lowest considering other data reported thus far. For IF locus, variability was also restricted to only one trible (Urubu-Kaapor) and attributed to a new polymorphic allele, IF* A3. PMID- 2094778 TI - A population cytogenetic study of a common fragile site, fra(3)(p14), in a healthy population. AB - A population survey of a common folate-sensitive fragile site, fra(3)(p14), was carried out on PHA-stimulated peripheral lymphocytes of 1,078 healthy subjects. Fra(3)(p14) was expressed more frequently in the younger than in the older, and in males than in females. It also showed some seasonal variation. The age difference of the expression frequency was also observed by aphidicolin treatment. A positive correlation of the expression frequency was found, though not so strongly, between both culture conditions of folate deprivation and aphidicolin treatment, These findings suggest that the inter-individual variation in the expressivity of common fragile sites is not only ascribable to chance, but to some physiological conditions of blood donors such as response rate of lymphocyte to PHA stimulation and blood concentration of folic acid. PMID- 2094779 TI - Monosomy for 21pter-q21: case report and assignment of a DNA clone (Fr8-77) to the deleted segment. AB - A 4-month-old Japanese girl with partial monosomy 21 was described. The patient has craniofacial anomalies, a short neck, wide-set nipples, anal atresia, deformed feet, hypertonia, intrauterine growth retardation, and mental deficiency. RFA- and high-resolution GTG-banding chromosome analyses, and Southern- and slot-blot analyses interpreted her karyotype as 45,XX,-2,-21, + der(2)t(2:21)(q37.3;q22.1). The origin of this de novo translocation ascertained by analyses with both QFQ-heteromorphisms and a Fr8-77/BamHI RFLP was paternal. Comparison of the patient with previously reported patients confirmed that her manifestations are consistent with those of monosomy for 21pter-q21. Based on the results of molecular analyses on the present patient, a DNA clone, Fr8-77 (D21S82), was assigned to pter-q21. PMID- 2094780 TI - Two unrelated cases of single maxillary central incisor with 7q terminal deletion. AB - Two unrelated cases of single maxillary central incisor (SM-CI) with 7q terminal deletion of the same breakpoint at 7q36.1 were described. They had mental retardation, microcephaly, hypotelorism, short stature, and normal levels of plasma growth hormone. One case had bilateral caudal ectopic kidneys, double renal pelves, and dilated ureters. The other had bilateral hydroureteronephrosis. The present cases suggest that 7q terminal deletion is one of the causes of SMCI. PMID- 2094781 TI - Isolation of a Y chromosomal DNA sequence and its clinical application. AB - A 4.6 kb long, Y-specific DNA fragment was isolated from a flow-sorted human Y chromosomal library, and its male specificity was confirmed by Southern blot analysis. The fragment, designated as pY-80, was proven with an in situ hybridization experiment to have originated from the Yp11.2-Ypter region. Its 2,808 bp section was sequenced. The polymerase chain reaction proceeded with oligonucleotides flanking a 666 bp PstI-EcoRI fragment of the sequence as primers and a male genomic DNA as a template, but not with a female genomic DNA. Preliminary tests of samples of various sources successfully detected the Y specific fragment in male-derived samples, including mouth wash, single hair roots, urinary epithelial cells, dried blood spots and amniotic fluid cells. PMID- 2094782 TI - Comparison between Bretschneider's total myocardial energy demand (Et) and our total mechanical energy (PVA) as a predictor of cardiac oxygen consumption in dogs. AB - We compared the predictive capability of two indexes of ventricular oxygen consumption (VO2) in excised cross-circulated dog hearts. One of the indexes was Bretschneider's Et, formulated as the sum of energies for 5 different mechanical and nonmechanical activities of myocardium. The other one was the left ventricular systolic pressure-volume area (PVA), originally proposed by Suga. PVA is a measure of total mechanical energy and has been combined with Emax (ventricular contractility index) to predict VO2 in different inotropic states. When all data sampled from different hearts under various loading and inotropic conditions were pooled, both VO2 (Bret) predicted from Bretschneider's index and VO2 (Suga) predicted from Suga's index correlated well with the measured VO2 (VO2 (Measured)). However, VO2 (Bret) was more affected by the contraction mode as compared with VO2 (Suga), because the former includes ejection period as a parameter. Among the 5 terms of VO2 (Bret), the major correlate of VO2 (Measured) was found to be tension development energy term E3 which includes dP/dtmax as a parameter. VO2(Suga), as a predictive index of VO2 (Measured), was more reliable in each heart than in pooled data from all the hearts because of the interindividual variations of the coefficients. We conclude that both indexes have usefulness and limitations, and should be chosen depending on the application. PMID- 2094784 TI - Regional distribution of vasoconstrictor tone in acute spinal rats. AB - Rats, chronically instrumented with an electromagnetic flow probe around the carotid, superior mesenteric, or renal artery, or the terminal aorta as well as having an arterial and venous catheter, were anesthetized with either and submitted to high spinal cord transection. One hour later, when the rats had recovered consciousness and the arterial pressure had recovered partially, hexamethonium was intravenously injected for ganglionic blockade. Peripheral resistance (arterial pressure/regional flow) was decreased significantly by ganglionic blockade in the carotid and renal areas but not in the superior mesenteric and hindquarter (terminal aortic) areas. This suggests the presence of sizable vasoconstrictor tone to resistance vessels in the carotid and renal areas but not in the superior mesenteric and hindquarter areas in the acute spinal rat. This distribution of vasoconstrictor tone is similar to that in intact conscious rats in the resting state and suggests the possibility that the vasoconstrictor tone for resistance vessels in intact rats is also for the most part generated in the spinal cord. Spinal transection decreased blood flow in all the four regions, suggesting a decrease in cardiac output due to dilation of capacitance vessels. It is possible that, in intact rats at rest, the so-called medullary vasomotor center is sending tonic impulses for the most part to capacitance vessels. PMID- 2094783 TI - Modulatory effects of endothelin-1 on central cardiovascular control in rats. AB - In urethane-anesthetized and immobilized rats, modulatory effects of endothelin-1 (ET-1) on central cardiovascular control were examined. An injection of 0.1 pmol of ET-1 into the cisterna magna caused immediate increases in arterial pressure (AP), renal sympathetic nerve activity (RSNA), and heart rate (HR) that lasted for 5-45 min. At doses of 1 and 10 pmol, intracisternal ET-1 elicited initial increases (phase I) followed by decreases in these variables below the pre injection level (phase II). At the dose of 1 or 10 pmol, the arterial baroreceptor reflex was suppressed during the latter part of phase I and during phase II. The three variables subsequently returned to, or often exceeded, pre injection levels in 30 to 60 min and reflex activity recovered (phase III). However, AP often remained below control throughout the 2-h observation period. Essentially identical responses to intracisternal ET-1 were observed in unanesthetized precollicular decerebrated or urethane-anesthetized rats. Application of a piece of filter paper soaked with 1 pmol of ET-1 to the ventral surface of the medulla (VSM) caused the pattern of changes similar to the following intracisternal injection. A microinjection of 4 pmol of ET-1 into the nucleus tractus solitarius (NTS) caused a moderate increase in RSNA with a minute fall in AP. Intrathecal administration of ET-1 resulted in moderate changes in AP and RSNA at the dose as high as 100 pmol. We conclude that intracisternally administered ET-1 modulates tonic and reflex control of AP and sympathetic vasomotor activity and that the VSM appears to be involved critically in this modulation. PMID- 2094785 TI - Effects of length change on intracellular Ca2+ transients in ferret ventricular muscle treated with 2,3-butanedione monoxime (BDM). AB - Quick release of the right ventricular papillary muscle of ferrets, injected with aequorin, from Lmax (initial length) to 92% Lmax during twitch response produced an extra-light signal of aequorin. 2,3-Butanedione monoxime (BDM) at 10 mM decreased the peak tension to less than 10% of that in control and the light signal to 70%. In the BDM-treated muscle, the extra-light in response to the quick release did not occur. A quick stretch from Lmax to 103% Lmax, in the presence and absence of BDM, did not cause any changes in the light signal. The results indicate that the extra-light signal in the quick release is tension dependent. The tension reduction by the quick release decreases the affinity of troponin-C (Tn-C) for Ca2+ without affecting Ca2+ handling system in intact cardiac muscle. PMID- 2094786 TI - Inhibitory effect of entopeduncular nucleus on the jaw-opening reflex induced by the tooth pulp stimulation. AB - The effect of stimulation of the entopeduncular nucleus (EP) on the jaw-opening reflex (JOR) was studied in the cat anesthetized with sodium pentobarbital. JOR was quantified by the digastric electromyogram. The conditioning stimulation (train of 33 pulses at 330 Hz, 0.5 ms duration, 50-400 microA) of the EP powerfully inhibited the JOR induced by the tooth pulp stimulation. Conditioning stimulation with 300 microA produced inhibition which continued approximately 400 ms from the cessation of the stimulation. The injection of monosodium glutamate into EP elicited inhibition of the JOR that lasted about 15 min. Additionally, the conditioning stimulation inhibited the JOR induced by the stimulation of trigeminal rostral and caudal nuclei in a similar manner but not jaw-opening response induced by the stimulation of the trigeminal motor nucleus. Therefore, it is possible that the excitation of the EP exerts inhibitory modulation of JOR at the motor nucleus rather than the trigeminal sensory nucleus. PMID- 2094787 TI - Effect of methamphetamine on rotational behavior induced by anodal polarization of the substantia nigra in rats. AB - The effect of methamphetamine (MAMP) on rotational behaviour was studied in rats after unilateral application of an anodal direct current (3 microA, 30 min) to the substantia nigra pars compacta (SNC). The current application induced a transient increase of contralateral rotation which declined within 30 min. An intraperitoneal injection of MAMP enhanced the effects of the direct current for more than 60 min. The results suggest that anodal direct currents induce activation of nigrostriatal dopaminergic system leading to increases in rotational behavior. PMID- 2094788 TI - Echinococcosis in Kenya: transmission characteristics, incidence and control measures. AB - Kenya has the highest reported incidence of human hydatid disease in the world. Up to about 30% of cattle, 15% of goats and 13% of sheep harbour the infection. The causative agent of the disease in Kenya is Echinococcus granulosus and a complex strain picture of this parasite has been postulated to occur. The domestic dog is the main definitive host of E. granulosus in Kenya but infection in wild carnivores has also been reported. Hydatid cysts have also been found in wild herbivores. Although the domestic cycle has been shown to be the most important mode of transmission of the disease, a sylvatic cycle is also known to exist. The etiology of hydatid disease, the strain differentiation of E. granulosus found in Kenya, and the role that wildlife plays in the transmission cycle is reviewed. The current trends in the incidence of hydatid disease in man and livestock, and the efforts being made to control the disease are also discussed. PMID- 2094789 TI - Human focal nodular hyperplasia-like lesion in the liver of a cat. AB - A young cat clinically displaying marked ascites had multiple nodule hyperplasia in the liver. One of the nodules sampled at exploratory laparotomy was studied histopathologically. The nodule consisted mainly of hyperplastic hepatocytes with a central stellate scarlike connective tissue. The connective tissue had thick walled blood vessels and radiating bands of fibrous connective tissue extending peripherally, dividing the nodule into pseudolobules. The lesions resembled focal nodular hyperplasia (FNH) in man. Serial section revealed a single large artery with the splitting of the internal elastic lamina running into the central connective tissue and branching to connect with the main vessels. The arterial branchings formed a spider-like structure. From these findings, it was suggested that the nodule had developed from a hepatic response to pre-existing vascular anomalies as had been reported in human FNH. PMID- 2094790 TI - Timing of sequential changes in chromosome configurations during the 1st meiotic division of pig oocytes cultured in vitro. AB - This study examines the timing of changes in chromosome configurations of pig oocytes derived from small antral follicles of follicular and/or inactive stage donors using modified 199 medium supplemented with gonadotropins (Follicle Stimulating Hormone (FSH), 10 IU/ml; Human Chorionic Gonadotropin (hCG), 10 IU/ml) and Glucosamine (0.539 mg/ml). Oocytes (n = 1,215) were fixed at the end of 3 hourly intervals from 0-48 hr of culture. Results were expressed as the percentage of oocytes at each stage of maturation for each time point. The germinal vesicle (GV) stage was observed for the first 17.6 hr; germinal vesicle breakdown (GVBD) stage between 17.6-26.4 hr; metaphase I (M-I) from 26.4-30.9 hr; anaphase I (A-I) ranged from 30.9-33.4 hr; telophase I (T-I) at 33.4-34.4 hr; and metaphase II (M-II) at 34.4-48 hr. PMID- 2094791 TI - Infectivity, reproductive capacity and distribution of Trichinella spiralis and T. pseudospiralis larvae in experimentally infected sheep. AB - Twelve Merino sheep were experimentally shown to be susceptible to infection with Trichinella spiralis or T. pseudospiralis by feeding on infected carcasses of mice or by oral intubation with recovered muscle larvae. The larvae recovered from the sheep showed variable tissue distribution. The diaphragm and tongue were most affected. The viability of the recovered larvae was confirmed by successful passage in mice. The reproductive capacity of T. spiralis in sheep was higher than that of T. pseudospiralis, and also higher than its reproductive capacity in C57BL/6J mice. The reproductive capacity of T. pseudospiralis in sheep at a lower dose was higher than that observed in mice. However at higher doses, it was significantly lower than that in mice. Therefore, it may be concluded that the sheep may be considered a suitable host for both species of Trichinella. PMID- 2094792 TI - [Congenital uterine anomalies in pregnancy]. AB - From 1984 to 1989, 805 infertile women were examined hysterosalpingographically and 127 (15.8%) proved to have one of the congenital uterine anomalies. The control group consisted of 45 fertile women with the anatomically normal form of the uterine cavity as was checked by the HSG method. Out of 127 patients, 4 (3.1%) had uterus unicornis, 76 (59.8%) arcuatus, 27 (21.35%) bicornis, 19 (15.0%) septus and 1 (0.8%) didelphys. In the group of 4 cases of the unicornuate uteri, only 1 had spontaneous abortion. In the group of 76 patients with the arcuate uteri, 11 (14.5%) had one or more spontaneous abortions and 4 (5.3%) premature delivery. Out of 48 pregnancies in this group, 14 (29.2%) ended with spontaneous abortion, and out of 24 deliveries, 4 (17.4%) were premature. There was a statistically considerably higher number of spontaneous abortions than in the control group (x2 = 49.8, p = 0.05). In the group of 27 patients with the bicornuate uteri, 12 (44.4%) had spontaneous abortion and 1 (3.7%) a premature delivery. Out of 25 pregnancies, 12 (48.0%) ended with spontaneous abortion, and out of 8 deliveries, 1 ended prematurely. Evident by, there was a considerably higher number of spontaneous abortions than in the control group (x2 = 24.2 p = 0.05). In the group with the septate uteri, out of 19 patients, 12 had spontaneous abortions and 4 premature delivery. Out of 34 pregnancies, 25 (73.5%) ended with spontaneous abortion, and out of 5 deliveries, 4 ended prematurely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094793 TI - [Drug therapy of Graves' disease in pregnancy]. AB - An analysis was made of 75 pregnant patients who received medicamentous therapy for Graves' disease before the investigated pregnancy and 20 healthy pregnant women with normal pregnancies and term delivery. A severe form of hyperthyreosis was found in 35 examined persons. A separate analysis was made of the patients who had no previous therapy (17) and pregnant patients who were treated with antithyroid drugs (18), with the aim to investigate their effect on the course and outcome of pregnancy and the condition of the newborn infant. In all examined pregnant women the median values with standard deviations for TSH, T4 and T3 in each trimester of pregnancy, the dynamics of their trends, as well as the correlation of values in treated and untreated pregnant women were recorded. The analysis of the pregnancy course in patients with hyperthyreosis indicated a significantly higher incidence of gestational diabetes and EPH gestoses (p less than 0.001). A separate analysis indicated that hyperthyreoidism is one of the risk factors in the occurrence of gestational diabetes. There were 90% of pregnant women who were delivered in an euthyroid condition achieved before pregnancy and maintained during pregnancy, 85% with mild and 77.1% with severe hyperthyreosis. The comparison of treated and untreated patients indicated that the percentage of delivered patients is similar (77.8:76.4), while the incidence of spontaneous abortions was higher (16.7:11.8) and of fetal deaths lower (5.5:11.8). There was one stillbirth in an untreated patient, while the remaining infants were healthy. The authors are of the opinion that it is necessary to achieve remission before pregnancy. In patients with severe hyperthyreosis the authors suggest the administration of antithyreoid drugs. PMID- 2094794 TI - [Value of the fetal biophysical profile in intensive monitoring of high risk pregnancy]. AB - The fetal biophysical profile (FBP) is a combination of both acute and chronic condition markers of the fetus in the uterus (fetal movements, fetal breathing movements, amniotic fluid volume, maturity of the placenta, intestine distension, cardiotocographic "non stress test", cardiotocographic "oxytocin stress test" cardiotocographic "physical stress test") presented numerically, is an irreplaceable method for monitoring the condition of the fetus in the uterus. In 271 women with high risk pregnancies at the gestational age of 34-44 weeks, depending on the FBP value, the time and mode of pregnancy termination were chosen. There is a significant difference regarding the outcome of pregnancy (general bad outcome--p less than 0.001, mortality--p less than 0.004, low 5 min Apgar score--p less than 0.002, fetal distress during labour--p less than 0.001) depending on the FBP value (normal or pathological) and the connection of the pathological FBP values with the low fetal biochemical profile values (estriol in 24th urine less than 40,000 n mol/day and HPL less than 5 mg). Sensitivity (46.4%), specificity (99.2%), the prognostic value of the pathological test PVP (86.7%), and prognostic value of the normal test - PVN (94.1%) show a high FBP value as a diagnostic test. It is necessary to stick to the protocol while using this test which is very simple, cheap and not at all harmful. PMID- 2094795 TI - [Perinatal outcome in older primiparas]. AB - Pregnancy, delivery and the newborn infant of 212 old primiparas (aged greater than or equal to 35 years) and of 1968 age-matched old multiparas as controls were studied for the 1970-1989 period. The frequency of old primiparas and old multiparas was 0.9% and 4.1%, respectively, with no change for the 1970-1979 (1.0%) and 1980-1989 (0.8%) periods. The mean age in the old primiparous and old multiparous groups was 38.08 + 4.2 and 38.2 + 4.8 years, respectively (P greater than 0.05). The old primiparas had an average of 7.37 +/- 2.8 antenatal visits, whereas the old multiparas had 6.08 +/- 3.3 visits (P less than 0.05). The old primiparous group included more employees and fewer unskilled workers and housewives (P less than 0.05), more urban and unmarried pregnant women (P less than 0.001), whereas the old multiparas had more spontaneous and induced abortions (P less than 0.05). Threatened abortion (23.7%), EPH gestosis (20.3%), meconium-stained amniotic fluid (21.7%), caesarean section (35.8%), placental lysis or uterine exploration (6.6%) and episiotomy (100.0%) are more frequent in old primiparas than in old multiparas (P less than 0.05). The duration of labour in old primiparas tends to be longer: there was a significantly smaller number of pregnant women with an up 6-hour duration of labour (42.5%; P less than 0.05). The average duration of labour in the old primiparous and old multiparous groups was 8.18 +/- 5.40 and 5.89 +/- 3.80 hours, respectively (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094796 TI - [Peroral and intracervical administration of prostaglandin E2 for stimulation of term labor in premature rupture of fetal membranes]. AB - The outcome of stimulation of labour in 219 primiparous patients with more than 6 hours following a premature rupture of the membranes, and with an ripe cervix, without the established labour, was analysed according to the mode of treatment. One hundred and thirty eight (138) women received PGE2 peroral tablets, 14 intracervical PGE2 gel, and 67 oxytocin intravenously. There were 73.2% vaginal deliveries in the group that received PGE2 per os, 77.5% in the group that received oxytocin, and 92.9% in the group that was given intracervical gel. The differences were significant. The cervix remained unripe in 9.4% patients that received PGE2 perorally, in 14.9% of those that received oxytocin, while in the gel group it became favourable in all parturients. Uterine polisistoly was encountered in 10.9% labours after peroral stimulation, in 7.1% in the gel group and in 1.5% in the oxytocin group, and perinatal asphyxia in 16.7%, 7.1% and 13.4%, respectively. When too frequent, especially if combined with oxytocin and given to patients with a moderately favourable cervix, peroral stimulation predisposes to uterine polisitoly. Intracervical application of PGE2 gel is the method of choice in primigravid patients with a premature rupture of the membranes and the unripe cervix (Bishop score O). In gravidas with a more favourable cervix (Bishop score 4-6) the administration of oxytocin is acceptable with less complications. In those with a moderately favourable cervix (Bishop score 1-4) the gel application proved to be preferable, although stimulation could be carried out as well. PMID- 2094797 TI - [Measurement of fetoplacental blood flow (resistance index) during labor with meconium stained amniotic fluid using the doppler technic]. AB - The blood flow in the fetoplacental circulation (umbilical artery) was examined by the Doppler technique in 42 labouring women with the meconium stained amniotic fluid. Ultrasound examination in the phase of cervical dilatation of 2-5 and 6-9 cm by the Doppler technique before and during contraction was carried out in each woman. Flow velocity wave-forms (FVW) of the umbilical artery were analysed by using the resistance index (RI). The ultrasonic apparatus Kranzbuhler ADR 8130 was used for measuring. The control group consisted of 54 labouring women with a clean, milky amniotic fluid. All resistance index (RI) mean values with the meconium amniotic fluid. All resistance showed a statistically significant decrease when compared to the group with the milky amniotic fluid (T = 5.91 p less than 0.01; t = 4.57 p less than 0.01; t = 5.73 p less than 0.01 t = 3.19 p less than 0.01). They probably are an indicator of the compensatory mechanism of the fetus. PMID- 2094798 TI - [Use of the CO2 laser in the treatment of pathologic changes in the vulva, vagina and uterine cervix]. AB - In the period from April 1987 to April 1990, 230 patients with pathological changes of the vulva, vagina and cervix uteri were treated with the CO2-laser. The diagnosis and pretreatment stages of the diseases were confirmed by the cytodiagnostic, colposcopic and histopathological results of the biophysics. In most cases, DNA-hybridization of human papilloma viruses confirmed their virus etiology. Twenty patients had peak condyloma of the vulva and vagina, 34 had benign cervical diseases, 65 were at the premalignant and 111 in the first stages of malignant cervical disease. Vaporizations, conical or cylindrical excisions were performed depending on the nature of disease and its localisation. The average age of operated patients was 30.6 years and the average parity 0.69. Operations were performed using analgesia and in rare cases total anesthesia. After the excision treatment, the tissue was checked histo-pathologically according to the principle of series. The complications were very rare. After operation, postoperative control was performed after 3.9 and 15 months, and later once a year. The results have shown that one treatment was sufficient in 80% of patients for curing vulvar and vaginal disease and 20% patients needed repeat because of the condyloma that relapsed. After the first treatment, benign and premalignant cervical diseases were cured in 100% of cases. In 95.4% operated patients at the first stages of cervical malignant diseases, the excisional treatment was final and in 4.6% needed an additional radical therapy because of a higher stage of lesion found by the conular histo-pathological analysis. There were no relapses relating to the cervix. PMID- 2094800 TI - [Convulsions in neonates and early neonatal mortality]. AB - The relationship between the early onset of convulsions in the early neonatal period and mortality was studied in 130 (0.26%) children with the birth weight exceeding 2,000 g in whom early neonatal convulsions were recorded. Early neonatal mortality in this group was very high reaching 25.4%. The peak mortality was noted in the first 12 hrs after birth (80.9%) and in the first 24 hrs (60.0%). In the cases of a postponed occurrence of convulsions, the mortality rate of neonates significantly decreases (p less than 0.01). PMID- 2094799 TI - [Pregnancy in women working on video terminal units]. AB - Only a small proportion of pregnancy failures could be explained by simple genetic or clear--cut environmental/occupational factors. Adverse reproductive outcomes (spontaneous abortion, preterm delivery, low birth weight and congenital malformations), have been reported in a certain number of retrospective studies which were designed to examine the possible role of occupation and working or living conditions and pregnancy outcome. Future prospective projects should assess the (non)existence of the relationship between radiological risks and job stress with pregnancy outcome. Future prospective projects should assess the (non)existence of the relationship between radiological risks and job stress with pregnancy outcome among female video terminal operators. PMID- 2094801 TI - Histones H1 and H4 are present near the replication fork. AB - The presence of histones H1 and H4 at the sites of actual DNA synthesis has been studied with Ehrlich ascites tumour cells, pulse labeled for different times with 3H-thymidine and then treated with formaldehyde to crosslink histones to DNA. The fixed chromatin fragments were sonicated to reduce the size of DNA, purified in a CsCl gradient and immunoprecipitated with antibodies to histones H1 and H4. Determination of specific radioactivity in precipitated probes showed that both histones have been associated with nascent DNA even upon 1 min pulse with 3H thymidine, thus indicating their presence near the replication fork. PMID- 2094802 TI - Effect of post-synthetic modifications of proteins on the binding of estrogen receptor complex to uterine nuclei of aging rats. AB - The binding of estrogen-receptor (ER) complex to nuclei following post-synthetic modifications of proteins was examined in the uteri of young (18 weeks) and old (96 weeks) rats. Acetylation decreases the binding of ER complex to nuclei but methylation shows no effect on the extent of binding in both ages. On the other hand, phosphorylation enhances the binding of ER complex by two-fold in nuclei from young rats but reduces this to half in nuclei from old rats. The pattern of binding in salt-resistant nuclear fractions is similar to that in total nuclei except in methylation where old rats show about 20% higher binding as compared to the respective control. These findings suggest that post-synthetic modifications of proteins modulate the binding of ER complex to uterine nuclei in an age specific manner. PMID- 2094803 TI - Furin is a subtilisin-like proprotein processing enzyme in higher eukaryotes. AB - The human fur gene encodes a protein, designated furin, the C-terminal half of which contains a transmembrane and a cysteine-rich receptor-like domain. The N terminal half of furin exhibits striking primary amino acid sequence similarity to the catalytic domains of members of the subtilisin family of serine proteases. We here report characteristics of the furin protein and propose a three dimensional model for its presumptive catalytic domain with characteristics, that predict furin to exhibit an endoproteolytic cleavage selectivity at paired basic residues. This prediction is substantiated by transfection and cotransfection experiments, using COS-1 cells. Full length fur cDNA evokes the specific synthesis of two polypeptides of about 100 kDa and 90 kDa as appeared from Western blot analysis of transfected COS-1 cells using a polyclonal anti-furin antiserum. Functional analysis of furin was performed by cotransfection of fur cDNA with cDNA encoding the 'wild type' precursor of von Willebrand factor (pro vWF) and revealed an increased proteolytic processing of provWF. In contrast, cotransfection of fur cDNA with a recombinant derivative (provWFgly763), having the arginine residue adjacent to the proteolytic cleavage site (arg-ser-lys-arg) replaced by glycine, revealed that provWFgly763 is not processed by the fur gene product. We conclude that in higher eukaryotes, furin is the prototype of a subtilisin-like class of proprotein processing enzymes with substrate specificity for paired basic residues. PMID- 2094804 TI - [Aminoacyl-tRNA synthetases (codases) and their noncanonical functions]. AB - The aim of this review is to summarize the data obtained in the author's laboratory during the last decade. The main objects of these investigations were mammalian aminoacyl-tRNA synthetases, mainly bovine tryptophanyl-tRNA synthetase (EC 6.1.1.2). The data are discussed and compared with those described in literature. In the course of these studies it turned out that some properties of mammalian aminoacyl-tRNA synthetases for instance, nuclear location of some of the synthetases, presence of extra-domain in bovine tryptophanyl-tRNA synthetase capable of catalyzing hydrolysis of ATP and GTP in the absence of Zn2+ ions and normal aminoacylation capacity, ability to bind to one of the glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase, formation of aminoacylated and pyrophosphorylated forms of tryptophanyl-tRNA synthetase etc., seem to be unrelated to the main function of the synthetases, catalysis of aminoacyl-tRNA formation, and, therefore, might be classified as noncanonical ones. Comparison of prokaryotic and eukaryotic aminoacyl-tRNA synthetases indicates the multipotential nature of the latter. PMID- 2094805 TI - [Structure-activity organization of leukocytic interferon]. AB - The recent experimental data on structure-function organization of leucocyte interferon are reviewed. The antiviral activity of the interferon molecule is supposed to be determined by more than two conformational centres. PMID- 2094806 TI - [Features of structure-activity organization of prolactin]. AB - The secondary structure of seven hormones of the prolactin family was predicted by two known prediction algorithms with the following averaging of the results for the whole homologous group of proteins. It was shown that the mentioned hormones are related to the alpha-helical type of protein molecules. The comparative analysis of the prolactin family and the kindred growth hormone family has been carried out on different levels of their structural organization. A conclusion is drawn, that despite the significant differences in the primary structures and small differences in the secondary structures, the three dimensional structure for the prolactin molecules and the growth hormone are very similar and repeat in the same way the packing of alpha-helices. The study of the relationship of the prolactin structure and function has been carried out. The regions of the amino acid sequence, able to form prolactin antigenic sites and conditionally incorporated into two highly specific spatial groups were revealed. The region of the primary structure 80-137 determining lactogenic and proliferational function of the molecule and forming the alpha-hairpin in the tertiary structure has been discovered. The structural particuliarity of one of the binding sites of prolactin and human growth hormone with lactogenic receptor was reveal. An explanation for the absence of lactogenic activity in all kinds of growth hormones except human ones has been proposed. PMID- 2094807 TI - [A kinetic model of peroxidation in a lipid bilayer]. AB - The structure, thermodynamic, and kinetic features of polyunsaturated fatty acids derivatives as the main substratum of lipid peroxidation (POL) have been considered. The heats of key POL reactions have been estimated. Kinetic consequences of these estimations have been analyzed. The dependence of POL rate on O2 concentration have been considered in detail both in the absence and in the presence of antioxidants. The essential features of POL processes in lipid bilayers resulting from the specific structure and molecular dynamics have been discussed. PMID- 2094808 TI - [Analysis of the amino acid sequence of homologous proteins on the personal computer "Iskra-226"]. AB - The presented software package allows: 1) to input and edit amino acid sequences; 2) to list aligned amino acid sequences of homologous proteins; 3) pairwise comparison of homologous sequences; 4) construction of phylogenetic trees; 5) comparison of two groups of protein sequences from the same family of homologous proteins; 6) graphic identification of conservative and variable regions of homologous sequences. The stepwise application of the programs allows to study the process of amino acid replacement accumulation during certain intervals of species evolution. PMID- 2094809 TI - [Activation of a trans-activating factor of NF1 transcription in a lactating mammary gland]. AB - Functional differentiation of a bovine mammary gland in the course of lactation is characterized by significant increase of tissue-specific expression of genes encoding milk proteins (caseins, lactoglobulin etc.). The NF1 is known as a ubiquitous transcription factor which modulates a tissue-specific transcription of different genes (including beta-casein) cooperating with tissue-specific and other ubiquitous transcription factors. We have observed a dramatic increase of NF1-binding activity in nuclear extracts of bovine mammary gland during lactation. The NF1 transcription factor appears to have a cytoplasmic precursor pool. This cytoplasmic precursor as well as NF-kappa B cytoplasmic precursor could be activated in vitro by deoxycholate (DOC) treatment which caused possibly dissociation of a complex of NF1 and its cytoplasmic inhibitor. There was an inverse proportion between concentrations of active nuclear NF1 factor and its cytoplasmic precursor. We have observed an increase of nuclear factor binding and a simultaneous decrease of the cytoplasmic precursor pool in the course of lactation. We have determined the NF1 protein subunit composition using UV-cross linking 32P labeled NF1-oligonucleotide with nuclear and cytoplasmic proteins of mammary gland. The main subunits of NF1 factor were p50 and p20. The drastic increase of nuclear NF1 binding activity was correlated with significant increase of the p20 subunit concentration in nuclear protein during lactation. PMID- 2094810 TI - [Phosphorylation of tryptophanyl-tRNA-synthetase by casein kinase type II]. AB - Incubation of tryptophanyl-tRNA synthetase from bovine pancrease with [gamma 32P]ATP of [gamma-32P]GTP and casein kinase II from rabbit liver leads to the incorporation of labeled phosphate into serine residues of synthetase polypeptide. The maximal level of 32P incorporation into synthetase polypeptide (Mr = 60 kDa) 0.15 moles of 32P per 1 mole of polypeptide was observed. Electrophoretic analysis according to O'Farrell showed that kinase phosphorylates exclusively the most acidic polypeptides (pI 4.9) of the synthetase preparation. Pretreatment of synthetase with animal acidic and alkaline phosphatases had no influence on the level of 32P incorporation in synthetase during subsequent incubation in the presence of casein kinase II. PMID- 2094811 TI - [Factor-free translation of poly(dT) by 80S ribosomes from Saccharomyces cerevisiae]. AB - The conditions for preparation of 80S ribosomes from S. cerevisiae are suggested. The ribosomes can bind Phe-tRNAPhe in poly(U)-or poly(dT)-directed manner and are shown to be able to translate poly(dT) in the absence of elongation factor and GTP. Effects of different antibiotics on the factor-free translation have been studied. PMID- 2094812 TI - [Modeling of hydration of incorrect nucleic acid base pairs by the Monte Carlo method]. AB - The hydration of water bridged base pairs of nucleic acids have been simulated via the Monte Carlo method. The simulation have shown that water molecules forming H-bonds with both bases preserve this H-bonding with large probability in the water surrounding. This fact supports the supposition about the important role of water molecules in wrong base pair formation and about the role of these base pairs in the structure and functioning of nucleic acids. PMID- 2094813 TI - [Features of the structure and evolution of complex, tandemly organized Bsp repeats in the fox genome. I. Structure and internal organization of the BamHI dimer]. AB - A 1468 b.p. DNA BamHI-fragment homologous to the Bsp-repeat was isolated from the fox genome and sequenced. This fragment is an hierarchically arranged dimer. Its 734 b.p.-monomers consist of three subrepeats (SR), each 245 b.p. long, abundant with overlapping imperfect tandem repeats which in turn are rich in short direct related repeats (each 4-7 b.p. in size). The latters are mainly composed of AG, TG dinucleotides and their complements CT, CA. All subrepeats in the BamHI-dimer are flanked by motifs homologous to Jeffreys' sites. At certain points the sites are doubled. The above data allow to assume that the Bsp-repeat complex structure is likely to have developed throughout long multi-step evolution of relatively simple DNA sequences which had emerged de novo. Single substitutions, small inserts and deletions, multiple duplication and recombination events seem to have most contributed to the evolution of the Bsp-repeats. Single substitutions in SRs with respect to the consensus are not equally distributed along their length. A wave-like pattern of this distribution is the evidence for non-random character of mutations accumulation. A correspondence was noted between conservative regions in SR and the presence therein of functional motifs homologous to the binding sites of already known regulatory proteins. PMID- 2094814 TI - [Formation of virus-like particles by HIV-1 Gag proteins, expressed by a recombinant vaccinia virus]. AB - Monkey kidney cells CV-1 were infected with recombinant vaccinia virus carrying HIV-1 gag gene with a deletion of 230 nucleotide pairs from the 3'-terminus. The main gene product detected in the lysates of infected cells was the gag precursor rp50. The protein was accumulated on the cell membranes suggesting that it had a myristylated N-terminus, and was cleaved by a recombinant virus specific protease with the formation of two proteins, p17 and p24 corresponding in molecular masses to mature gag proteins. Virus-like particles similar to immature HIV virions were budding from the surface of infected cells. They look like the ring of optically dense material covered with a lipid bilayer, of the same size (100-120 nm) and of the same density in a sucrose gradient (1.16-1.18 g/ml) as HIV-1 virions. The particles contained rp50 and cellular heterogeneous RNA. Thus, the unprocessed gag precursor with deleted 77 amino acid residues from the C-terminus is able to form virus-like particles in the absence of env proteins and virus-specific RNA, and these particles are budding from the cell surface. The question about the use of extracellular Gag-particles for AIDS diagnostic work and construction of vaccines is discussed. PMID- 2094815 TI - [Organization of genes of ribosomal RNA from the mushroom Verticillium dahliae]. AB - Using yeast probe, a complete ribosomal DNA unit from a plant pathogenic fungus, Verticillium dahliae, was cloned into a plasmid vector pTZ19R. Partial DNA sequence of the clones, when compared to the yeast ribosomal DNA sequence, allowed to establish the physical map of the fungal rDNA. The overall organization was shown to be similar to other fungal rDNAs previously known. PMID- 2094816 TI - [The effect of Cephalotaxus group alkaloids on elongation of the polypeptide chain in human ribosomes]. AB - Effects of Cephalotaxus alkaloids (homoharringtonine and cephalotaxine) on the translation of endogenous mRNA in a cell-free system of rabbit reticulocyte lysate and on poly(U)-directed poly(Phe) synthesis on human placenta ribosomes was studied. The effect of the alkaloids on the activity of human placenta ribosomes in a template-dependent aminoacyl-tRNA binding, N-acetyl-phenylalanyl puromycin and diphenylalanine formation was also studied. Homoharringtonine was shown to have little effect of codon-dependent Phe-tRNA(Phe) binding but the alkaloid strongly inhibited (Phe)2 formation as well as N-Ac-Phe-puromycin synthesis from the complex N-Ac-Phe-tRNA(Phe).poly(U).80S ribosomes. It was concluded that the site of homoharringtonine binding overlaps or coincides with the acceptor site of the ribosomal peptidyltransferase center. The association constant of homoharringtonine to the ribosomes was estimated to be (4.8 +/- 1.0) x 10(7) M-1. Cephalotaxine had no effect on the elongation steps. PMID- 2094817 TI - D2 dopamine receptor gene expression by cholinergic neurons in the rat striatum. AB - In situ hybridization with D2 receptor probe and immunohistochemistry with choline acetyltransferase (ChAT) antibody performed on adjacent sections demonstrate dopamine D2 receptor gene expression in cholinergic neurons of the rat caudate-putamen and nucleus accumbens. Eighty per cent of cholinergic neurons in the striatum contain detectable D2 receptor mRNA. The other neurons without detectable D2 mRNA do not display specific localization or aspect in the caudate putamen and nucleus accumbens as compared to the other cholinergic neurons. The absence of detectable D2 mRNA in certain cholinergic neurons can be due to the limited sensitivity of the procedure that would not detect low mRNA levels, or alternatively can reflect the existence of two cholinergic cell populations in the striatum, one of which would not express the D2 receptor gene. The other forebrain cholinergic neurons do not contain D2 mRNA. PMID- 2094819 TI - Recurrent dorsal root potentials and motoneuron morphology in the frog spinal cord. AB - About one third of motoneurons stimulated intracellularly evoked dorsal root potentials (DRP) in the lumbar segments of the isolated and perfused frog spinal cord. Axon collaterals were found in one of the 22 motoneurons filled with HRP (horseradish peroxidase) through the stimulating electrode. In further experiments injecting individual motoneurons with cobalt, and filling the ventral roots with HRP or cobalt, the frequency of occurrence of axon collaterals was about 2% of the number of labelled motor cells. It is suggested that the presence of motor axon collaterals is not indispensable in the generation of the DRP evoked by ventral root or motor cell stimulation. PMID- 2094818 TI - Parietal projection of thalamocortical fibers from the ventroanterior ventrolateral complex of the cat thalamus. AB - Anterograde labelling following focal injections of Phaseolus vulgaris leucoagglutinin was used to identify the parietal distribution of thalamocortical (TC) fibers from the ventroanterior-ventrolateral (VA-VL) complex of the cat thalamus. In injections in the ventrolateral or the caudal part of the VA-VL complex, labelled TC fibers were distributed in layers I, III and IV of the parietal areas 5a and/or 5b, whereas in injections located more rostrally or dorsomedially, labelled TC fibers were almost confined to layer I. PMID- 2094820 TI - Action of baclofen, GABA and antagonists on the membrane potential of cultured astrocytes of rat spinal cord. AB - The action of gamma-aminobutyric acid A (GABAA) and B (GABAB)-agonists has been studied on the membrane potential of astrocytes in explant cultures of rat spinal cord by means of intracellular microelectrode recordings. The GABAB-agonists (-) baclofen and CGP 27 492 (3-aminopropyl phosphonous acid; 10(-6) to 10(-4) M) caused a hyperpolarization of the majority of astrocytes studied. On approximately 25% of the cells, the compounds had no effect. The hyperpolarization by baclofen (10(-4) M) was reversibly antagonized by the GABAB antagonist 5-hydroxysaclofen (10(-4) M). GABA and the GABAA-agonist muscimol (10( 4) and 10(-3) M) depolarized approximately two thirds of the glial cells tested, whereas the remaining third remained unaffected. The GABAA-antagonist bicuculline (10(-4) and 10(-3) M) only reduced the depolarization by GABA (10(-4) M) but did not completely block it. On half of the cells tested, the depolarization by GABA was not affected by bicuculline, suggesting that the glial GABAA-receptor is different from the neuronal GABAA-receptor. Our electrophysiological investigations together with recent autoradiographic binding studies strongly suggest the existence of GABAB-receptors on astrocytes whereas there is less evidence for GABAA-sites on these cells. PMID- 2094821 TI - Application of principal component analysis for characterizing convergence patterns of inputs in interneurones of the cat forelimb segments. AB - We attempted to quantitatively describe a variety of convergence patterns of inputs from peripheral nerves and descending tracts (13 sources) onto interneurones of the cat forelimb segments (C6-C8). To this end we applied principal component analysis using the latency of firing as the parameter of each input. The first 3 principal components thus obtained explained 65% of the total variance of convergence patterns and characterized the input pattern of each cell. The first principal component correlated mainly with inputs from pads and the median nerve, the second with the cortico- and rubro-spinal tracts and the third with the superficial radial nerve. PMID- 2094822 TI - Interleukin-1 beta and tumor necrosis factor-alpha synergistically stimulate nerve growth factor (NGF) release from cultured rat astrocytes. AB - Nerve growth factor (NGF) may mediate responses to brain injury. To examine regulation of NGF gene expression with respect to neural trauma we examined the effects of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) on NGF production in cultures of rat astroglial cells. Purified neocortical astrocytes in serum-free medium were treated with IL-1 beta, TNF alpha or both. Whereas IL-1 beta and TNF-alpha alone elicited only small effects, simultaneous addition elicited within 48 h a large (3- to 6-fold) increase in NGF content in culture supernatants. Our data are consistent with a role for cytokines in NGF synthesis and release in the injured central nervous system (CNS). PMID- 2094823 TI - Cell modulation of hydrophobic tailed 16S acetylcholinesterase by intracellular calcium in rat superior cervical ganglion neurons. AB - In primary cell cultures of rat superior cervical ganglia (SCG) the tailed asymmetric 16S molecular form of acetylcholinesterase (AChE) possesses hydrophilic (high-salt soluble, HSS) and hydrophobic (detergent extracted, DE) variants. Hydrophobic tailed acetylcholinesterase is associated with membranes through a glycolipid anchor. In the presence of tunicamycin, an antibiotic which inhibits protein glycosylation, the cellular amount of the hydrophobic DE 16S AChE is increased. Exposure of the cells to the calcium ionophore A 23187 leads to a decrease in DE 16S AChE and a correlated increase in hydrophilic HSS 16S AChE. These results suggest the existence of an endogenous processing of tailed AChE, transforming the hydrophobic variant into an hydrophilic one controlled through glycosylation and intracellular calcium. PMID- 2094824 TI - Ammonia is endogenously generated in the brain in the presence of presumed and verified dementia of Alzheimer type. AB - The healthy, mature, non-starved brain was found to take up a small amount of ammonia on average 7.22 +/- 0.72 micrograms/100 g x min. In contrast, in patients thought to be suffering from incipient early-onset dementia of the Alzheimer type (DAT) the brain released a larger amount of ammonia on average 25.59 +/- 16.17 micrograms/100 g x min. In advanced DAT states, an average of 2.73 +/- 0.32 micrograms/100 g x min was released indicating the temporary nature of the severe loss of amino-N during the early stages of presumed DAT. Detrimental effects of endogenously formed ammonia on brain metabolism may affect the membrane potential, the excitability of neurons, and the energy metabolism. Ammonia may be assumed to be involved in the morphological changes in astrocytes and in the gliosis observed in early degeneration related to DAT. Endogenously generated brain ammonia thus may have a role in the cascade of cell damaging events in presumed incipient DAT. PMID- 2094825 TI - You and the GST blues. PMID- 2094826 TI - Mortgage watch. A case study. PMID- 2094827 TI - The inside story. An interview with ODA President Dr. Bill Leggett. Interview by Jordana Halpern. PMID- 2094828 TI - Niobium filter v. an aluminum filter. PMID- 2094829 TI - 3-D Analyzer. PMID- 2094830 TI - Occlusion and dentistry. PMID- 2094831 TI - Use and misuse of radiographic imaging in the diagnosis and treatment of temporomandibular joint disorders. PMID- 2094832 TI - [A propedeutic concept: the pathologic physiognomy of organs]. AB - After a brief philologic introduction on some correlated concepts of pathogenesis we suggest the concept of pathological physiognomy of the organs. This concept express the conditioning that the peculiar structure, topography and function of an organ exercise on the characteristic configuration (and sometimes even on the possibility) of a pathological process in it. As fondament of this concept we report several examples of pathology. PMID- 2094834 TI - [Nephropathy in rheumatoid arthritis]. AB - Occurrence of renal involvement in Rheumatoid arthritis is uncommon; when present it has been attributed to amyloid or secondary effects of drugs. Nevertheless, recent observations seem to indicate the existence of primary renal lesions associated with the disease. The purpose of this paper is to review the data suggesting that the kidney can be directly involved in Rheumatoid arthritis. The main points of interest are the occurrence of glomerulonephritis and/or amyloidosis, the presence of vasculitis and other arterial changes, the existence of chronic interstitial nephritis and papillary necrosis and lesions associated with gold and penicillamine therapy. PMID- 2094833 TI - Hypoxic right ventricular cardiomyopathy. A morphological and pathogenetic study on the myocardial atrophy and fatty infiltration. AB - The autopsy report of an asymptomatic, non familial cardiomyopathy with widespread fatty infiltration of the right ventricular wall in two alcoholic subjects, who were also heavy smokers and suffering from a serious laryngeal obstruction, led the Authors to investigate, on the basis of a thorough review of the literature, the possibility that hypoxia, alcoholism and smoke could have caused the development of the cardiac lesion. The presence of myocardial fatty infiltration is explained, under conditions of high-flow hypoxia, by the reduced fatty acid oxidation. The higher tissue levels of fatty acyl-CoA, fatty acyl carnitine and alpha-glycerophosphate thereby lead to the increased conversion of the FFA into tissue lipids. Under hypoxic conditions there is also an increased polyols synthesis. The reduced conversion of dyacylglycerol into phosphatidic acid causes its tissutal increase and the interaction with fatty acyl-CoA to produce triacylglycerol and CoASH. In alcoholic patients reduced oxidation and increased FFA synthesis is sustained by the altered mitochondrial respiratory control and excess of acetate, with the consequent increase in acetyl-CoA, fatty acyl-CoA and alpha-glycerophosphate concentration. In addition, fatty acid ethyl esters normally absent in the myocardium are formed. The fact that, in hypoxic or alcoholic subjects with cardiomyopathy, an impaired myocardial contractility has been noted as the most relevant haemodynamic factor may be explained by both the reduced energy production following the decrease in aerobic glycolysis and FFA oxidation, and specific genetic changes that lead to both the production of a myosin with lower Ca2 + ATPase activity and a reduced protein (and therefore myofibrillar) synthesis. This fact can result in a severe atrophy of the cardiac myocytes. The lower their contractile activity, the more evident the process of atrophy. The lesion principally affects the right ventricle for both metabolic and anatomical reasons. It has been shown how, under normal conditions, the RV metabolism is suited to a relatively reduced O2 supply situation, with a high lactate dehydrogenase and alpha-hydroxybutiratedehydrogenase activity. It is more likely to be affected therefore whenever there is a chronic state of high-flow hypoxia. While alpha-HBDH allows the RV extensive utilization of ketone bodies as an energy source, its notable increase under hypoxic conditions further increases the synthesis of fatty acids and therefore fatty infiltration of the myocardium. The relatively lower capacity for oxygen extraction and lower tissue perfusion of the RV compared with the left ventricle make an adequate oxygen supply in the case of increased O2 demand even more difficult.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2094835 TI - [Transplant glomerulopathy. Anatomohistopathologic and ultrastructural aspects]. AB - 14 cases of transplant glomerulopathy have been observed in 254 specimen taken from 152 renal allografted patients. Lesions have been studied at light, immunofluorescence and ultrastructural level. Following morphological parameters have been evaluated by semiquantitative method: focal mesangial sclerosis, mesangial matrix, mesangial cellularity, glomerular basement membrane thickening, double contours and crescents. Intermediate and advanced stages prevailed with the evidence of capillary aneurysms in 2 out 14 cases. Electron microscopy showed thickening of the glomerular basement membrane with finely lamellar and electron lucent thickening of the lamina rara interna. Transplant glomerulopathy lesions need differential diagnosis with thrombotic microangiopathy and can be considered equivalent of chronic vascular rejection. PMID- 2094836 TI - [Adenolymphoma and microadenolymphoma. Histomorphogenetic considerations]. AB - Histomorphogenetic considerations. Seventy three consecutive cases of parotid adenolymphoma were studied. Clinical data (age, sex, site, diagnostic hypothesis, type of surgery), macroscopy (examination of all nodules associated with adenolymphoma and related topography), microscopy (morphological analysis by means of conventional stainings, histochemistry, immunohistochemistry, semiquantitative and morphometric evaluations), with special regard to the lymphoid stroma, were correlated in order to investigate histo-morphogenetic aspects. In 44 cases, lymph nodes were detected (156:83 intraparotid and 73 periparotid). In 18 cases the adenolymphoma resulted multifocal. In 14 of them multifocality was due to the presence of only microscopic (clinically unsuspected) additional adenomas in intraparotid lymph nodes (20 microadenolymphomas). A further microadenolymphoma with 6 associated lymph nodes was occasional finding in a case of sialadenitis. Inclusions of salivary epithelium were observed in 46 intraparotid lymph nodes, were metaplastic (different types of metaplasia) in 23 of them, and were associated with 16 microadenolymphomas. Inclusions and microadenomas were both absent in periparotid lymph nodes. This study strongly supports the intralymphonodal histogenesis of the adenolymphoma and emphasizes the role of the ductal metaplastic changes of the salivary inclusions in the development of the adenomatous proliferation. A model of morphogenetic evolution (with related diagnostic problems) from intralymphonodal inclusions to microadenolymphoma and successively to clinical tumour (macroadenolymphoma) is proposed on the basis of the sequential rearrangement of the various morphological and morphofunctional observations. With special reference to the characteristics of the lymphoid stroma, a minor role of specific immunological mechanisms in the etiopathogenesis of the adenolymphoma is suggested. PMID- 2094837 TI - [AIDS pathology: various critical considerations (especially regarding the brain, the heart, the lungs, the hypophysis and the adrenal glands]. AB - Our studies on pathology of AIDS point to four major conclusions. 1) The brain is often directly affected by the HIV infection (with the characteristics of subacute microglial encephalitis with pathognomonic multinucleated giant cells) and then by opportunistic infections such as Cytomegalovirus, Herpes-virus, Papova-virus JC (with progressive multifocal leucoencephalopathy), Mycobacterium tuberculosis, Toxoplasma gondii, Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus; opportunistic neoplasms (i.e. B cell lymphoma mostly pluricentric) could also developed. 2) The heart is frequently involved as well; perivascular sclerosis and myocytolysis are the hallmarks of a peculiar cardiomyopathy. 3) In the lung viral, bacterial, fungal an protozoan severe infections are frequently present: common are those caused by Cytomegalovirus and Pneumocystis carinii. Frequently thin fibrotic interalveolar septa are observed (with consequent alteration of hematosis). 4) Adrenal (most frequently) and pituitary may display necrotic-hemorragic areas (in adrenals chiefly due to Cytomegalovirus). These may be extensive enough to explain the occurrence of clinical syndromes of endocrine insufficiency. PMID- 2094838 TI - [Clinico-diagnostic aspects of chronic pancreatitis]. AB - Chronic pancreatitis are mainly classified as chronic calcifying pancreatitis (CCP) and chronic obstructive pancreatitis (COP). The first classification was performed in 1963 and reproposed in 1984. Clinical symptoms and natural history of chronic pancreatitis are presented. Pre-operative clinico-radiological findings may be pathognomonic of the disease. Endoscopic retrograde cholangio pancreatography (ERCP) and per-operative pancreatography and cholangiography are extremely useful for diagnostic purpose. Chronic pancreatitis may induce local inflammatory complications (pseudocysts, chronic serosal effusions, fistulae) duodenal stenosis and segmental portal hypertension. A strict correlation of clinico-pathological findings is very important in the diagnostic procedure of chronic pancreatitis. Intraoperative diagnosis (either histologic, either cytologic) is of paramount importance in the diagnosis of a pancreatic mass. Histology is prominent in the definition of the specific form of pancreatitis. PMID- 2094839 TI - [Anatomopathologic pictures of chronic pancreatitis]. AB - Morphology of pancreas (either esocrine, either endocrine) was studied in 29 cases of surgically treated chronic pancreatitis (27 cases of chronic calcifying pancreatitis and 2 cases of chronic obstructive pancreatitis). Parenchymal sclerosis in chronic calcifying pancreatitis (CCP) which represents the goal of our study was graded as mild (10 cases), moderate (10) and severe (7). Immunoperoxidase staining (PAP method) for insulin, glucagon, somatostatin, pancreatic polipeptide (PP), vasoactive intestinal polipeptide (VIP) and gastrin, was used to investigate endocrine pancreas. Acinar sclerosis and endocrine damage were closely related. Progression of sclerosis into islet appears to follow vascular pedicles producing a fragmentation into small cell groups as final result. In all cases of moderate or severe sclerosis, A/B cell ratio was increased due to the reduction of insulin positive cells. "Adenoma-like complexes", i.e., apparent concentration of islets, resulting from the loss of the acinar component, were observed in 7 cases with moderate or severe sclerosis. Nesidioblastosis was a prominent feature in all cases but one, with a positivity for insulin in 11 cases, for glucagon in 13, for somatostatin in 6 and for PP in 17. No positivity for gastrin was observed, while VIP was detected in a few ganglia. An increased amount of PP cells in islet and budding from the ducts was noticed and their presence outside the pancreatic head was demonstrable in 4 out of the 7 distal pancreatectomy specimens. Our data confirm the secondary involvement of the endocrine pancreas in the sclerotic acinar process. PMID- 2094840 TI - [Fine needle aspiration of pancreatic masses. A study of 81 cases]. AB - Study of 81 cases. Fine Needle Aspiration Biopsy (FNAB) was performed under computerized thomography scan (CT) in 81 patients with documented pancreatic mass (54 with neoplasia and 27 with chronic pancreatitis). This procedure, when associated to the immediate cytological evaluation of the adequacy of the smears, permits to obtain 100% in sensibility, specificity and predictive value of positive cases. These results and the study of the literature confirm CT-guided FNAB of the pancreas as the procedure of choice to resolve problems of differential diagnosis in pancreatic masses. PMID- 2094842 TI - [Clinico-pathologic considerations on 9,952 appendices removed at the Busto Arsizio Hospital from 1966 to 1989]. AB - The histological examination of all the surgically removed appendices at the Busto Arsizio Hospital started in 1966. Several interesting pathological features were recognized, together with a significant change of the clinician's attitude toward "appendicopathies". Elmintiasis was relatively frequent especially in the cases operated before 1980; the decrease of this condition may be due to the improvement of the hygienic conditions. There were 53 carcinoid tumors, more frequently in young females. Some time histology simulated malignancy, not confirmed by the biologic behavior. Several other pathologic conditions were observed, and retained occasionally responsible of the abdominal symptoms. In the more recent years a relatively large number of appendices were removed during surgical procedures for other pathological conditions. The most surprising results concern however the decrease of the number of appendectomies performed yearly (755 in the late 60s, vs. 160 more recently) as well as the elevation of the age of the operated patients. The systemic histological examination of the appendix and the accurate recording of clinicopathological data is therefore a recommended procedure for a quality control of both the surgical and the anatomopathological activities. PMID- 2094841 TI - [Helicobacter pylori and gastro-duodenal pathology]. AB - Helicobacter Pylori (HP) were found in 878 (73%) of 1205 patients undergoing upper G-I endoscopy with multiple biopsies for gastroduodenal diseases. HP were present in similar percentages among patients with active (89%) or healed (81%) peptic ulcer as well as in non ulcerous dyspeptics affected with gastritis (85%). 96% of active chronic gastritis were infected by HP as compared with 55% of quiescent gastritis. Antral gastritis was more frequently active in patients with ulcer diseases (76%) than in dyspeptic and asyntomatic patients (50%). Healed gastric and duodenal ulcers showed decreased incidence of active antral gastritis (69) as compared with active ulcers. Conversely body gastritis was more frequently active in healed (37%) than in overt (18%) duodenal ulcers. 95 histologically normal stomachs as well as 9 cases exhibiting type A gastritis were devoid of HP. High rates of infection were found in 610 cases of chronic gastritis without atrophy as well as in 151 atrophic antral (type B) gastritis. Cytoplasmic vacuolization and swelling of foveolar-superficial cells with adhering bacteria, micropapillae and microerosions were commonly found in HP infected mucosa. In 16 of 19 children with type B chronic gastritis antibacterial therapy eradicated HP. This was followed by resolution or striking improvement of gastritis and disappearance of epithelial lesions. PMID- 2094843 TI - [Loosening of total hip prosthesis]. AB - The problem of total hip prosthesis is an immediate and long-term stability. An insufficient bone anchorage of the prosthesis produces a tissue reaction around the implant that causes a loosening. The hight incidence of loosening of cemented total prosthesis has spurred the research into uncemented implants. The experience at the Busto Arsizio Hip Center (Director Prof. R. Bombelli) with more than 2,800 R.M. uncemented isoelastic total hip prostheses was favorable and the study with the cooperation of Pathology Department (Director Prof. P. Lampertico) of the 82 loosening hips has shown: 1) the importance of the elasticity for a stress transmission to the surrounding bone; 2) the pursuit of the most suitable stem calibre and length; 3) the necessity of a stable primary mechanical fixation, waiting for a biological reaction. PMID- 2094844 TI - Dentists' hearing and exposure to high speed turbine dental drill noise. AB - Effect of high speed turbine dental drill noise (DDN) on dentists' hearing at present and during the era of noisier drills was investigated. Hearing of two generations of dentists, power spectral density (PSD) functions of DDN from various drills and the equivalent level (LAeq) of a modern dental operatory were studied. The LAeq was 65 dB with 1 and 50% probability distribution levels of 74 and 57 dB, respectively. DDN was tonal with the spectrum peak always above 6 kHz, containing within 128 Hz frequency band 28-85% of the total noise energy in the PSD function. A cartridge type ball bearing drill from early 1960's was found noisier than an air bearing drill or a modern sealed head ball bearing drill by 8.5 and 5 dB, respectively. Sound pressure levels of DDN ranged from 68 to 79 dBA, being within safe limits. The high values earlier reported for cartridge type or worn drills could not be verified. Hearing of dentists free from clear ear pathology was found good and very similar to the reference, representing a population with no exposure to noise. There was no difference in hearing of 46 dentists 33-42 years of age, examined in 1973 and among whom there had been exposure to early and noisier drill, as compared to hearing of 56 dentists of similar age and years in dentistry, examined in 1988 and who had only been exposed to quieter drills of the 1970's. Noise dose and audiometric measurements were in agreement and indicated that DDN is not and has never been a risk to dentists' hearing. PMID- 2094845 TI - Coverage of public oral health services for young children in Finland. AB - In the Finnish programme of public oral health care for preschool children, every child is eligible for free care. The coverage of the programme has been high, about 85%. The aim of this study was to determine, whether the nonparticipants of the programme actually do have equality in making the choice to participate. The barriers to care were identified. All 4- to 6-year-old children who were registered administratively as nonparticipants in oral health care in 1981 and their randomly selected controls were studied in the city of Lahti. Detailed analysis of nonparticipation showed that some children had been misclassified as nonparticipants in the administrative statistics, indicating the national coverage of the programme to be higher than reported. Based on this finding, suggestions are made for increasing reliability of official statistics. Multiple logistic regression analysis for 36 factors resulted in three main barriers to utilization. Children of single-parent families in which the parent had a low level of education and difficulties to take time off work had the highest risk of nonutilization and thus had little choice to participate. Children with fear to dental care, regardless of any characteristic of the family or parents, were at increased risk of nonparticipation. Not having received the invitation to an examination also increased nonutilization, regardless of any factors related to family, parents or child. It was concluded, however, that these barriers to utilization could be manipulated by the system of public oral health care. PMID- 2094846 TI - Clinical and panoramic assessment of marginal bone loss. A cadaver study. AB - The purpose of this study was to investigate the reliability of panoramic tomography for the assessment of marginal alveolar bone loss. The study was conducted with 20 human cadavers, in relation to 123 of their teeth. Panoramic tomograms of the cadaver dentitions were taken using a Zonarc radiographic apparatus. Root lengths and bone losses were measured mesially and distally from the panoramic tomograms. Bone loss was also measured by surgical exposure of the marginal bone. Root length was also measured after extraction of the tooth. After allowing for the vertical magnification, radiographic bone loss values were found to be about 0.8 mm (27%) less than clinical values. This difference was statistically significant only in the incisor area. It was almost significant in the premolar region. It is therefore concluded that panoramic tomography is sufficiently reliable for clinical assessment of alveolar bone loss but that the bottom of periodontal pockets always tends to be somewhat deeper than the radiographically visible defect. PMID- 2094847 TI - Caries occurrence in Klinefelter syndrome men (47,XXY males). AB - Men with the Klinefelter syndrome (47,XXY males) and their brothers were studied as regards their caries experiences as part of a comprehensive study on oral facial growth and health in individuals with sex chromosome anomalies. The results show that caries experience was greater among the 47,XXY men than among their normal brothers, and a greater proportion of the 47,XXY men's cumulative caries experience consisted of extractions. PMID- 2094848 TI - Immediate reconstruction of mandibular defects with revascularized iliac bone grafts after radical surgery for osteosarcoma. AB - Excluding multiple myeloma, osteosarcoma is the most frequent primary malignant bone tumor. However, it is rare in the jaw bones, where it mainly occurs in young adult men. This report describes two mandibular osteosarcomas found in two males aged 32 and 30. In the former patient, osteosarcoma developed after bilateral mandibular sclerotic changes had been diagnosed radiologically as cementifying fibroma. This patient had received radiation therapy (56 Gy) because of a high grade astrocytoma of the brain three and a half years earlier. In the latter patient the tumor arose de novo in the mandibular molar area. The initial main symptom both patients was pain, which had been considered to be of dental origin because radiographs showed no evidence of malignancy. Radical surgery using immediate mandibular reconstruction with revascularized iliac bone grafts gave good results in both cases. The former patient died eight months after surgery because of recurrent astrocytoma and the latter is now free of disease five years after surgery. Immediate reconstruction of mandibular defects is possible with osteocutaneous groin flaps. PMID- 2094849 TI - Forensic dentistry--recent development towards an independent discipline in modern dentistry. AB - Since the late 1890s, forensic odontology has gradually established itself as important, often indispensable, in medicolegal cases, in particular for identification of the dead. The specialty of forensic dentistry generally covers three basic areas, namely, (1) identifications human remains, (2) litigation relating to malpractice, and (3) criminal proceedings, primarily in the areas of bite-mark evaluation and child abuse. Much of its expertise is based on clinical experience, fundamental research and advances in knowledge in relation to dentistry in general. Particularly over the past two decades, there has also been increasing research on specific forensic dental matters. In this paper, the methods of identification used in forensic dentistry are reviewed, and their application in two areas, mass disasters and bite-mark analysis is discussed. Progress in this field in Finland has been relatively slow. It has depended as in other countries on development of training and research facilities in the dental schools, and oral pathology departments. PMID- 2094850 TI - A biopsychosocial approach to TMJ pain--or looking for keys in the dark. AB - A biopsychosocial model for understanding TMJ dysfunction is presented. The balance between biological, psychological and sociological factors involved in TMJ dysfunction and low back pain is described. If only one of these factors is treated the result may be favourable; however, if the others are neglected, the favourable result may be only temporary. PMID- 2094851 TI - Initial comparison between endoscopic and conventional methods of caries diagnosis. AB - This study was designed to assess the feasibility and practicability of the employment of endoscopic methods for the diagnosis of dental caries and to compare the diagnostic performance, in posterior teeth, of visual endoscopic caries diagnosis (with and without the benefit of differential fluorescence) with that of conventional visual diagnosis, bite-wing radiography, and conventional transillumination. The two endoscopic methods were found to be clinically practicable, to be able to demonstrate the presence of small carious lesions, and to have both advantages and disadvantages compared to conventional methods. When all tooth sites were compared, the results indicated that the endoscopic methods may detect a greater number of carious lesions than do conventional visual, radiographic, or fiber-optic transilluminational methods of caries diagnosis. Further investigations involving histologic validation of diagnoses as well as larger numbers of patients and multiple examiners are indicated. PMID- 2094853 TI - Fracture strength of Class I versus Class II restored premolars tested at the marginal ridge. I. Standard preparations. AB - Two groups of maxillary premolars with Class I cavities were prepared with one marginal ridge thickness to a width of 1.0 mm. One group was restored with amalgam and the other group with composite resin. Two groups of Class II cavities also were prepared and restored with amalgam and composite resin. The teeth in the four treatment groups were subjected to a centric load at the marginal ridge until fracture occurred. A two-factor analysis of variance revealed a statistically significant difference between the class of preparation (Class I preparations were weaker than were Class II preparations) but differences in strength between restorative materials (composite resin versus amalgam) and the interaction effect (class of preparation x restorative materials) were not found to be statistically significant (alpha = .05). A Newman-Keuls sequential range test found no statistically significant differences in strength between groups (alpha = .05). Fracture patterns were observed under scanning electron microscope. Fractures extended into the enamel and into the material in the Class I composite resin, Class I amalgam, and Class II composite resin restorations. Fractures extended only into the material in Class II amalgam restorations. PMID- 2094852 TI - Fluoride uptake in bovine enamel and dentin from a fluoride-releasing composite resin. AB - To determine the fluoride uptake in enamel and dentin, a fluoridating composite resin was fixed at a 100-microns distance from bovine enamel and dentin for 2 weeks. The results revealed a substantial increase in the level of fluoride in both enamel and dentin. This model investigation showed that the fluoride released by the composite resin was effectively taken up by the surrounding tissues. The fluoride released from the composite resin and the subsequent uptake by the tissues would be expected to protect against secondary caries. PMID- 2094854 TI - Treatment of the severe Class III edentulous patient with implant-retained prostheses. AB - Certain difficulties exist that make it hard to construct a complete set of dentures for the Class III edentulous patient. With the advent of osseointegrated implants, many of these difficulties can be overcome and patients can now look forward to stable and retentive prostheses that do not have to be removed. By careful assessment of the patient and meticulous attention to detail during the surgical and prosthodontic phases of treatment, predictable long-term results can be achieved. PMID- 2094855 TI - A technique for the construction of complete dentures in two visits. 2. A pilot study to evaluate the opinions of practitioners and patients. AB - The technique for fabrication of complete dentures in two visits was described in part I. The purpose of the present study was to evaluate both the clinical methods used and patients' acceptance of the resulting dentures. Eleven general practitioners were taught to use the technique and then asked to complete a questionnaire. Most practitioners had some difficulty with some aspects of the technique. The consensus was that the two-visit denture technique would have some application in providing low-cost dentures, provided that the esthetic demands of the patient could be satisfied within the limitations of the technique. The second part of the evaluation was provided by patients, who were asked to indicate a preference between two sets of dentures, one made using a four-visit technique and the other using the two-visit technique. Preferences were divided, but all patients were able to wear both sets of dentures. The final responsibility for providing an adequate denture service remains with the practitioner. PMID- 2094856 TI - Finite element analysis of fixed prostheses attached to osseointegrated implants. AB - The effect of defined stresses on cantilevered prostheses attached to osseointegrated implants was assessed by finite element analysis. The effect of stress on a cantilever, consisting of a ductile alloy in contact with a brittle polymer, was demonstrated to be complex. The distribution of applied stresses also influenced the results. Possible fracture and distortion of both materials were demonstrated. Finite element analysis is a particularly useful system for predicting stress behavior and can be employed to produce an optimal prosthetic design that reduces the potential for clinical failure. PMID- 2094857 TI - Dental twinning anomalies: the nomenclature enigma. AB - Dental twinning results from abnormal events in the embryologic development of teeth. This paper describes the impossibility of assigning precise diagnostic terms, such as germination, fusion, macrodontia, and concrescence, to dental twinning anomalies because the entire course of odontogenesis cannot be witnessed. Traditional nomenclature is reviewed and seven cases that exemplify the principle are presented. Modification of nomenclature to describe dental twinning defects is suggested. PMID- 2094858 TI - Adhesion monomers utilized for fixed partial denture (porcelain/metal) repair. AB - A technique is presented for repair of fatigue-fractured fixed partial dentures with an overlaid, bonded porcelain/metal repair. The repair techniques utilize recent advances in resin-to-metal and resin-to-porcelain adhesion. Clinical procedures are given for adhesion of repair castings to intraoral porcelain or metal surfaces. Metal surface preparation techniques depend on the chemistry of the metal and include intraoral tin plating of noble metals. Direct adhesion of composite resin luting agents is used for base metals. PMID- 2094859 TI - Evaluation of temperature rise on the outer surface of teeth during root canal obturation techniques. AB - The heat generated at the apical 2 mm of the outer root surface of extracted human canine teeth during three obturation procedures was measured. The rise in temperature was found to be less when a sealer was used in all obturation techniques. Temperatures as high as 44.02 degrees C were recorded with warm gutta percha with no sealer, and the lowest temperature rise occurred with a thermoplasticized gutta-percha technique with a sealer. The thickness of the remaining dentin and cementum after cleaning and shaping were found to have no effect in reducing temperature rise. The results of this investigation indicated that temperature rise on the outer surface of the root as a result of heat generating obturation procedures is negligible and will not have an effect on the supporting attachment apparatus. PMID- 2094860 TI - Apexification: review of the literature. AB - Five methods for the treatment of teeth with an incompletely formed apex (open apex) and a necrotic pulp are discussed. The methods discussed include the use of (1) a customized cone (blunt-end, rolled cone); (2) a short-fill technique; (3) periapical surgery (with or without a retrograde seal); (4) apexification (apical closure induction); and (5) one-visit apexification. The apexification techniques, which use various formulations of calcium hydroxide to induce closure, are stressed. Based on the review of the literature and clinical experience of the authors, it was concluded that successful treatment of an immature pulpless tooth can partly result from the antibacterial and calcification-inducing action of calcium hydroxide. PMID- 2094861 TI - Modification of clinical usage of periodontal curettes. AB - Periodontal curettes are used extensively for root preparation in periodontal therapy. The traditional method of root scaling and planing is found in standard periodontics textbooks. A modification of the clinical usage of peridontal curettes that might be useful to clinicians in daily dental practice is described. PMID- 2094862 TI - Patient's right to life--a student's right to live. PMID- 2094863 TI - Triplication and twinning in one dental arch: report of a case. AB - This report documents the case of a young patient who presented with dental conjoining anomalies in both sides of the maxillary arch. One defect involved primary incisor twinning and the other a rare instance of primary incisor triplication--three conjoined teeth. PMID- 2094864 TI - Effect of a denture adhesive on mandibular denture dislodgment. AB - The cineradiographic technique was used to assess the retention of complete mandibular dentures during chewing. The study comprised ten complete-denture wearers with severe alveolar ridge resorption in the mandible. Two cineradiographic recordings were performed, with and without a denture adhesive spread onto the base of the mandibular denture. The analysis of the cineradiographic films disclosed a significant decrease in denture dislodgment, expressed as maximal value, when a denture adhesive was used. The mean dislodgment also decreased, but not significantly. PMID- 2094865 TI - Analysis of resistance and retention of complete veneer crown retainers. AB - The resistance and retention of a fixed partial denture are influenced by the number and distribution of the abutment teeth that support it, the path of insertion, the shape of the arch to which it must conform, and the occlusal relationship it will have with the opposing teeth. If the prosthesis is to be designed properly, it is necessary to understand how each of these factors influences the stability of the prosthesis and its ability to resist dislodgment. If the conditions that contribute to the instability of the prosthesis are misunderstood, overlooked, or ignored, it is impossible to design a prosthesis that will be predictably successful. PMID- 2094866 TI - Augmentation of incisor width with bonded composite resin: another look. AB - One of the most gratifying composite resin bonding procedures for patients and dentists alike is closure of unwanted and unsightly interdental spaces. Various methods of performing such bonding have been described. The most modern composite resins are strong, tooth-colored materials that can exactly simulate the appearance of normal tooth structure and reliably stay in place for many years. A method of augmenting the mesiodistal coronal dimension of anterior teeth without mechanical preparation of the enamel described. PMID- 2094867 TI - Removal of "black-line" margins and improving esthetics of porcelain-fused-to metal crowns: update in technique. AB - A repair technique is presented for elimination of "black line" crown margins and extension of margins onto cervical surfaces. A resin bonding agent that adheres simultaneously to metal, porcelain, and dentin is utilized to expedite completion of the repair. The bonding resin is opaqued with a light-curing, filled resin and then covered with a suitable composite resin. This technique updates a previously published technique by eliminating glass-ionomer cement liners and liner etching and improves both efficiency and esthetics of the repair. PMID- 2094868 TI - Use of the acid-etch technique to maintain antimicrobial-containing acrylic resin strips in situ. AB - A technique that utilizes acid-etched composite resin to maintain antimicrobial containing acrylic resin strips in situ is described. The advantage of this technique is that placement of a periodontal pack is unnecessary, so control of supragingival plaque is not hindered at the site of the local antimicrobial delivery. The technique described may improve the effectiveness and the clinical acceptability of local antimicrobials in the treatment of periodontal disease. PMID- 2094869 TI - An in vitro study of the diffusibility of intracanal medicaments. AB - In this study, the diffusion properties of the vapors of four canal antiseptics were examined. Tricresol, camphore-chlorophenol, Cresophene, and povidone-iodine in clinical doses were tested against Staphylococcus aureus and Streptococcus faecalis. Forty-five extracted human maxillary central incisor teeth were used, and their root canals were prepared. A small amount of antiseptic was placed on a cotton pellet in the pulp chamber of each tooth, and the chamber was sealed with Cavit. Vapors from each of the test medicaments produced zones of inhibition on Staphylococcus aureus and Streptococcus faecalis. The study showed that vapors of the test medicaments do pass through the apex of a tooth and thus have a potential effect at the periapical area. The largest zone of inhibition resulted from the vapor of tricresol. PMID- 2094870 TI - Fracture strength of Class I versus Class II restored premolars tested at the marginal ridge. 2. Cavosurface bonding and cavosurface plus internal enamel bonding. AB - The purpose of this study was to test the difference between the strength of the marginal ridge of extracted teeth with a Class I composite resin restoration and the strength of the marginal ridge of teeth with a Class II amalgam restoration with retention grooves. A statistically significant difference in fracture strengths was found among groups. No statistically significant difference was found among restored preparations, beveling technique, and restorative material. Statistically significant differences in fracture strength were found between the whole tooth group and treatment groups; between the whole tooth group and Class II amalgam restoration group; and between the unrestored tooth preparation group and all other tooth groups. PMID- 2094871 TI - Effect of fluoride release from a fluoride-containing composite resin on secondary caries: an in vitro study. AB - The effect of fluoride, released from a fluoride-containing composite resin, on secondary caries was investigated by quantitative microradiography. In all teeth investigated, less demineralization was found near the composite resin than was found at a distance of a few millimeters from the material after an acid attack. The presence of the fluoride-releasing composite resin reduced the lesion depth measured after an acid attack by about 35%. Therefore, in vivo, a reduction of recurrent caries may be expected around fluoride-containing composite resins. PMID- 2094872 TI - Relationship between critical convergence angle and surface defects in stone casts. AB - Surface defects on stone casts threaten the accuracy of cast restorations. The aim of this study was to examine the relationship between critical convergence angle and voids in stone casts. Three addition silicone materials, one condensation silicone material, and one polyether impression material were used. The highest convergence angle at which voids presented at the tip of the specimens was recorded, and the number of voids found at margins and line angles of the tooth preparations were counted. Results showed a positive and significant correlation between the critical convergence angle and the number of voids at margins and line angles of stone casts. Casts poured from polyether impressions registered significantly lower critical convergence angle values and presented with fewer voids than did those fabricated from silicone materials. PMID- 2094873 TI - Repair of defective Class I composite resin restorations. AB - Composite resin restorations undergo dimensional changes that can eventually result in marginal defects. Unlike silver amalgam restorations, which usually should be completely removed before the tooth is restored again, bonded composite resin restorations can often be repaired. This report demonstrates a step-by-step technique for repairing a defective Class I composite resin restoration with a new application of resin after elimination of the defect. The method has proved successful over the last 8 years. PMID- 2094874 TI - Direct technique for the fabrication of a visible light-curing resin provisional restoration. AB - A properly fabricated provisional restoration will, among other things, provide acceptable esthetics. Although many materials have been used for provisional restorations, when esthetics is of primary concern, the choice is limited to tooth-colored resin materials. Recently, a tooth-colored, light-activated urethane dimethacrylate resin has been developed. This material has been reported to be useful for many prosthetic applications, including the indirect fabrication of provisional restorations. This paper presents a technique for the direct fabrication of single-unit provisional restorations using this material. The physical properties of this resin and the advantages and disadvantages of the technique are also discussed. PMID- 2094876 TI - Combined orthodontic and restorative correction of severe anterior open bite. AB - This article describes a multidisciplinary approach to the treatment of a severe skeletal anterior open bite, complicated by severe chronological enamel hypoplasia, in a 12-year-old southern Chinese girl. Correction of the open bite, of which the cause was unknown, involved the extraction of all first permanent molars and provisional repair of the wafer-thin enamel to permit bonding of fixed orthodontic brackets. Several phases of maxillary and mandibular fixed appliance therapy followed. As the open bite resolved, further restorative treatment was performed. The result was stable 3 years after the end of retention. This case demonstrates the benefits of well-planned, integrated, multidisciplinary treatment. PMID- 2094875 TI - Guided tissue regeneration: observations from five treated cases. AB - In this clinical investigation, a biodegradable collagen material was used in membrane and paste form to assess its suitability for use in guided tissue regeneration after surgery. A variety of healing responses in only the soft tissues were noted, ranging from gross necrosis to enhanced healing. The problems and limitations of regeneration procedures are discussed to explain the reasons for the observed healing of the tissues. PMID- 2094877 TI - Lightening of dark radiographs with a superproportional reducing agent. AB - Copper sulfate reducer is useful for lightening and improving the diagnostic quality of dark radiographs. The solution consists of copper sulfate, sodium chloride, and sulfuric acid. The radiograph is immersed and bleached in the solution until it turns white, redeveloped in weak developer, and fixed. Reduction is superproportional; that is, the percentage of reduction is greater in darker areas than it is in lighter areas. The degree of reduction increases with increased density. The degree of reduction decreases with increased redevelopment time. The reduced radiograph may have a gray, brown, or black image. Resolution is increased on the reduced radiograph. PMID- 2094878 TI - Operating illumination to differentiate dental hard tissues. AB - This in vitro study was designed to evaluate the ability of fluorescent tubes and dental lights to help operators distinguish tissues (fissures), differentiate between tissues (at the dentinoenamel junction or between carious and sound dentin), and distinguish form of a tooth preparation (Class II and Class V cavities). Operators with "normal" color vision ranked the lights in order of preference for each type of specimen. In general, for the fluorescent illuminants, operators preferred lights with high color temperature values and high color rendering index values. A small group of color-blind observers indicated a preference for an illuminant of low color temperature and low color rendering index value. For dental lights, operators preferred a higher color temperature for examining fissures, the dentinoenamel junction, and the cavity preparation. No particular illuminant was preferred for distinguishing between carious and sound dentin. Many observers had difficulty in choosing a preferred dental luminaire. PMID- 2094879 TI - [Method-related complications of balloon catheter valvuloplasty of heart valve stenosis in children and adults]. AB - Within a short term of 7 years percutaneous valvuloplasty of congenital and acquired stenosis, the cardiac valves and the great central vessels has significantly improved. If strict criteria for the selection of patients are used the method is an important addition to cardiac therapy, since it requires no thoracotomy, no heart lung machine surgery, no complicated interventional follow up treatment and gives remarkable short and long term results. Starting from a thorough study of 300 publications (4836 patients) a survey of possible complications, their frequency and in percutaneous valvuloplasty is given for various methods. The compiled data and commentaries give a negative survey and shall lead to a new evaluation of indications. Some types of interventions (primarily the percutaneous rupture of degenerative calcified stenosis of the aortic valve in higher age) will lead only by significant improvements of technique (stabilization of myocardiac circulation, prevention of extreme hypotonic phases, use of cutting and sawing instruments: valvuloplasty under cardioscopy?) to acceptable long term therapy results. PMID- 2094880 TI - [Percutaneous transvascular pulmonary valvuloplasty. Early and late results]. AB - Since the introduction into practice in may 1986 at the Institute of Cardiovascular Diagnostics we performed 45 valvuloplasties until March 1990 in 34 children (6.2 +/- 4.9 years old) and 11 adults (29.5 +/- 9.6 years) with valvular pulmonary stenosis. The invasively obtained pressure gradient at the valve diminished from 83.4 +/- 30.7 mm Hg to 35.7 +/- 19.0 mm Hg. Intraoperative complications in three patients (short term asystole, severe bradycardia, increase of right ventricular pressure to 300 mm Hg after valvuloplasty) were controlled, but demanded the end of the intervention. No significant insufficiency of pulmonary valves after valvuloplasty was seen. 18 patients were clinically investigated 14.6 +/- 9.4 months after intervention. The late results for these patients proved the method as a long term curing treatment. According to our present results pulmonary valvuloplasty is the alternative method for valve surgery especially in critical pulmonary valve stenosis in newborns. PMID- 2094881 TI - [Percutaneous pulmonary balloon dilatation in complex congenital defects]. AB - Since several years percutaneous balloon dilatation has gained more and more importance as a method circumventing thoracotomy. Induced by the results in the international literature [1-14] we performed successfully percutaneous pulmonary balloon dilatations in 8 patients between June 1988 and March 1990. Three patients (aged 6.5 to 27 years) had an isolated, prevailing valvular pulmonary stenosis, while the five others had a complex congenital anomaly with valvular and subvalvular pulmonary stenosis. The paper reports the results of pulmonary balloon dilatations in the latter five patients. PMID- 2094882 TI - [Persistent and patent ductus arteriosus. Different forms and sizes]. AB - In 563 consecutive heart catheter investigations in sucklings, infants and children 109 open ducti were diagnosed. 75 children (13.3%) had a ductus arteriosus persistens (DAP) and 34 a ductus arteriosus (DAA). We were able to measure 89 ducti. Groups were formed according to the age of the children, of DAP or DAA and the intended treatment. The sizes of the ducti constitute a set of data for improving the methods for closure or newly developed transvasal methods of conservation of the ductus as an aortopulmonary shunt. PMID- 2094883 TI - [A methodologic variant in transarterial closure of a persistent ductus arteriosus]. AB - The most severe complications in transarterial closure of the ductus arteriosus persistens are problems with placing the plug into the ductus (misfit plug size/ductus size) and the flow of closure materials into the aorta after instable fixation of the plug. In such cases surgical intervention by arteriotomy or aortotomy for the removal of the plug becomes necessary. Transvenous dilatation of the ductus arteriosus persistens after recognizing unstable plus positions or difficulties in fixing the plug prevents the mentioned complications. PMID- 2094884 TI - [Castaneda-de Leval's modified Fontan operation in complex cyanotic defects with subsequent percutaneous transluminal embolization of systemic pulmonary collaterals]. AB - The case of a five year old boy with a double-inlet-left-ventricle and the aorta in 1-malposition, large VSD, ASD and pulmonary stenosis is reported, that showed after modified Fontan surgery severe effusions and a severe protein loss syndrome. Aortopulmonary collaterals were detected as the cause of this and successfully treated in several sessions by percutaneous transluminal embolization. PMID- 2094886 TI - [The possible significance of coronary vascular resistance in chronic ischemic heart disease]. AB - From a pool of patients, treated because of cardiac diseases on ward for 4 years, 8 subjects, the mean age of which amounted to 46 (SD 12) years, showing stable angina pectoris in usual physical activity, were chosen. In these patients widespread examinations including invasive procedures had not been evident for one of the well defined heart diseases. In two patients dysrhythmias appeared during standardized exercise test while in four other subjects acute cardiac findings consisted of chest pain, significant depression of ST segments or inversion of T waves were observed. One patient had a normal result of the exercise test. A myocardial thallium-201 imaging was performed in four subjects. In three patients imaging showed questionable or mild signs of ischemia. The result suggest the existence of unknown shapes in coronary heart disease, the origin of which is possibly connected with a disorder of microvascular smooth muscle reactivity. PMID- 2094885 TI - [Semi-invasive measurement of pulmonary pressure as a method of evaluating cardiac function in hypertension and ischemic heart disease. Experience at Charite Hospital for more than 20 years]. AB - Since 1969, microcatheterization (floating catheterization) of the pulmonary artery has systematically been used at the Hospital Charite in Berlin for measuring (indirectly) the left ventricular filling pressure. That seemed especially be justified in patients in whom conventional catheterization was not needed. Noninvasive techniques had not been available. Since then, our interest was focused on the hypertensive heart, earlier under the aspect of early discovering and influencing heart insufficiency, later concerning a developing myocardial ischemia, in relationship to left ventricular hypertrophy. At the Charite more than 1,000 microcatheterizations in more than 400 hypertensive cases have been performed, mostly in combination with nuclear-cardiological measurements. The rate of complications was found minimal. Thus, cardiac function could be characterized hemodynamically, at rest and even under ergometric load. Special programmes served the acute application of drugs for diagnostic or therapeutic reasons. In the meantime a longterm study could also be finished by using hemodynamic measurements, starting with hygienic means and followed by a antihypertensive basis therapy, in newly detected hypertensives. That included repeated catheterizations of the pulmonary artery. PMID- 2094887 TI - Central haemodynamics after orthotopic heart transplantation. PMID- 2094888 TI - [Emergency coronary surgery in patients with unstable angina pectoris. Results and place in the total concept of the treatment of this group of patients]. AB - The urgent coronary surgery performed in patients with high risk unstable angina (rest pain greater than 48 h) shows still different results. We found in 57 urgent operated patients the same functional and clinical results as after elective bypass grafting. A higher in hospital mortality after urgent coronary surgery based on a higher number of grafts are occluded in the early postoperative period. The better prognosis concluded that the use of urgent coronary surgery is the therapy of choice in patients with refractory unstable angina pectoris. PMID- 2094889 TI - [Feasibility and limitations of evaluating the severity of mitral and aortic insufficiency using Doppler color echocardiography]. PMID- 2094890 TI - The prefrontal cortex--its structure, function and pathology. Amsterdam, The Netherlands, 28 August-1 September 1989. PMID- 2094891 TI - Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. AB - The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits. Admittedly, the anatomical evidence upon which this scheme is based remains incomplete. The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals. Only in the case of the "motor" circuit has evidence for the continuity of the loop been demonstrated directly in individual subjects; for the other circuits, such continuity is inferred from comparisons of data on different components of each circuit obtained in separate experiments. Because of the marked compression of pathways leading from cortex through basal ganglia to thalamus, comparisons of projection topography across experimental subjects may be hazardous. Definitive tests of the hypothesis of maintained segregation await additional double- and multiple-label tract-tracing experiments wherein the continuity of one circuit, or the segregation of adjacent circuits, can be examined directly in individual subjects. It is worthy of note, however, that the few studies to date that have employed this methodology have generated results consistent with the segregated circuits hypothesis. Moreover, single cell recordings in behaving animals have shown striking preservation of functional specificity at the level of individual neurons throughout the "motor" and "oculomotor" circuits. It is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits. This is not to say, however, that we expect the internal structure of functional channels (e.g., the "arm" channel within the "motor" circuit) to have cable-like, point-to-point topography. When the grain of analysis is sufficiently fine, anatomical studies have shown repeatedly that the terminal fields of internuclear projections (e.g., to striatum, pallidum, nigra, thalamus, etc.) often appear patchy and highly divergent, suggesting that neighboring groups of projection cells tend to influence interdigitating clusters of postsynaptic neurons. While more intricate and complex than simple point-to-point topography, however, this type arrangement should also be capable of maintaining functional specificity. As discussed briefly above, it is not yet clear to what extent the inputs to the "motor" circuit from the different precentral motor fields (e.g., MC, SMA, APA) are integrated in their passage through the circuit. It now appears that at the level of the putamen such inputs remain segregated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2094892 TI - Prefrontal cortical control of the autonomic nervous system: anatomical and physiological observations. PMID- 2094893 TI - The development of the rat prefrontal cortex. Its size and development of connections with thalamus, spinal cord and other cortical areas. PMID- 2094894 TI - Neuronal development in human prefrontal cortex in prenatal and postnatal stages. PMID- 2094895 TI - Structural and histochemical reorganization of the human prefrontal cortex during perinatal and postnatal life. PMID- 2094896 TI - Anatomical correlates of behavioural change after neonatal prefrontal lesions in rats. PMID- 2094897 TI - Age-dependent effects of lesioning the mesocortical dopamine system upon prefrontal cortex morphometry and PFC-related behaviors. PMID- 2094898 TI - Is it possible to repair the damaged prefrontal cortex by neural tissue transplantation? AB - The techniques are now well established for the viable transplantation of cortical and other neural tissues into the neonatal and adult cortex, at least in the laboratory rat. Under appropriate conditions such grafts survive well and can establish reciprocal connections with the host brain. On this basis, neural transplantation has become a powerful technique for the study of mechanisms involved in the development of the central nervous system and its capacity for regeneration after injury. Moreover, a variety of anatomical, electrophysiological and behavioural techniques suggest that grafted neural tissue may sustain functional interactions with the host brain. However, the extent and duration of recovery using present techniques is extremely limited. It remains undetermined whether such experimental observations may ever acquire therapeutic application. PMID- 2094899 TI - Enhanced cortical maturation: gangliosides in CNS plasticity. PMID- 2094900 TI - How sensory cortex is subdivided in mammals: implications for studies of prefrontal cortex. AB - A problem for studies of all cortex, including prefrontal cortex, is how to relate results to proposed subdivisions of the brain and how to compare results across species. Investigators have been highly dependent on traditional architectonic maps of neocortex. However, over the last 20 years, other methods, especially the microelectrode mapping method, have been applied to regions of sensory cortex, where orderly representations of receptor surfaces have provided strong evidence for new proposals of how cortex is subdivided. As a result, we can more reliably indicate functional subdivisions of cortex and identify valid homologies across species. Obtaining accurate maps of functional subdivisions of prefrontal cortex in a range of mammalian species is an important goal in that such maps are basic to interpreting other data. While microelectrode mapping methods may be more difficult to apply to prefrontal than sensory cortex, a range of useful anatomical and histochemical methods are available. Studies of sensory cortex suggest that all mammals have a few sensory areas in common, and that additional areas have evolved in some lines. One approach toward a better comparative understanding of frontal cortex might be to investigate the possibility that primary motor cortex, the supplementary motor area, and the frontal eye field are areas that exist in most or all mammals, and use these fields, when they can be clearly demonstrated, as reference areas for further studies on how frontal and prefrontal cortex is subdivided. PMID- 2094901 TI - Qualitative and quantitative comparison of the prefrontal cortex in rat and in primates, including humans. PMID- 2094902 TI - Behavioral electrophysiology of the prefrontal cortex of the primate. AB - The prefrontal cortex (PFC) is critical for temporal organization of behavior. It mediates cross-temporal sensorimotor contingencies, integrating motor action (including speech) with recent sensory information. It performs this role through cooperation of 2 cognitive functions represented in its dorsolateral areas: short term memory (STM) and preparatory set. Supporting data have been obtained from monkeys performing delay tasks, which epitomize the principle of cross-temporal contingency. In a given trial, the animal performs an act contingent on a sensory cue given a few seconds or minutes earlier. During the delay between cue and response, cells in dorsolateral PFC show sustained activation. Two cell categories can be identified in tasks in which cue and response are spatially separate. Cells of the first participate in STM: Their activation tends to diminish as the delay progresses; in some, the activation level depends on the particular cue received. Similar cells are found elsewhere in the cortex. Cells of the second category seem to take part in preparation of motor response: Their activation tends to increase in anticipation of it and may be attuned to the particular movement the cue calls for. This cell type is rare outside of the frontal cortex. The temporally integrative function of the PFC is probably based on local interactions between "memory" and "motor-set" cells, as well as on neural associations between PFC and posterior cortical areas. PMID- 2094903 TI - Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates. PMID- 2094904 TI - Distributed neuroelectric patterns of human neocortex during simple cognitive tasks. PMID- 2094905 TI - Influence of the ascending monoaminergic systems on the activity of the rat prefrontal cortex. PMID- 2094906 TI - The determinants of stress-induced activation of the prefrontal cortical dopamine system. PMID- 2094907 TI - Involvement of mesocorticolimbic dopaminergic systems in emotional states. PMID- 2094908 TI - The neurobiological basis of prefrontal cortex self-stimulation: a review and an integrative hypothesis. PMID- 2094909 TI - Role of the prefrontal--thalamic axis in classical conditioning. AB - The major conclusion to be drawn from the above-described research on the role of the PFCag in classical conditioning is obviously that it plays a primary and perhaps necessary role in the establishment of visceral cues associated with exposure to classical conditioning contingencies. Specifically, these visceral changes appear to be of an inhibitory character. This is significant, since we have postulated that inhibitory cardiac changes invariably accompany initial processing of sensory stimuli for informational value. Such visceral changes are thus not epiphenomena associated with other simultaneously occurring physiological events. A variety of lesion experiments implicate the PFCm as a central structure in this process, since damage to this area greatly attenuates, and in the case of hypothalamic knife cuts, completely eliminates learned bradycardia. Neuroanatomical tract-tracing experiments revealed that the PFCm and lag have direct projections to the NTS and DVM in the dorsomedial medulla and the nucleus ambiguous in the ventral medulla, all of which provide medullary output control of visceral activities. The nucleus ambiguous and DVM have been specifically implicated in vagal control in the rabbit (Ellenberger et al., 1983). Electrical stimulation of the PFCm provides additional evidence that this area of the brain participates in parasympathetic activities, including cardiac inhibition, since stimulation of the entire MD projection cortex, including the PFCm, produces HR decelerations accompanied by depressor responses. However, since lesions of the Iag produced relatively little effect on conditioned bradycardia, this part of the PFCag does not appear to play a major role in the development of conditioned bradycardia. Electrophysiological recording studies, including both multiple unit as well as extracellular single unit studies reinforce these conclusions. A short latency (40-180 msec) CS-evoked increase in MUA was recorded from cells in both the dorsomedial as well as central PFCm. The magnitude of these CS-evoked neuronal changes (a) was correlated with the magnitude of concomitantly occurring conditioned bradycardia; (b) was trial related; (c) was not obtained in a similar pseudoconditioning group; and (d) declined to pretraining levels during subsequent experimental extinction. Similar, but not identical, CS-evoked changes in neuronal activity were recorded from MD. Although tone-evoked increases in MUA were also obtained from the Iag, this activity did not show the characteristics of associative learning. Single unit analysis also suggests the importance of the PFCm in elicitation of conditioned bradycardia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2094910 TI - Functions of anterior and posterior cingulate cortex during avoidance learning in rabbits. PMID- 2094911 TI - Social behaviour and the prefrontal cortex. PMID- 2094912 TI - Animal models for human PFC-related disorders. PMID- 2094913 TI - The prefrontal cortex in schizophrenia and other neuropsychiatric diseases: in vivo physiological correlates of cognitive deficits. PMID- 2094914 TI - The prefrontal area and psychosurgery. PMID- 2094915 TI - Neurometric studies of aging and cognitive impairment. PMID- 2094916 TI - Prefrontal cortex in relation to other cortical areas in rhesus monkey: architecture and connections. PMID- 2094917 TI - The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: evidence for a parallel organization. AB - Recent findings in primates indicate that the connections of the frontal lobe, the basal ganglia, and the thalamus are organized in a number of parallel, functionally segregated circuits. In the present account, we have focused on the organization of the connections between the prefrontal cortex, the basal ganglia and the mediodorsal thalamic nucleus in the rat. It is concluded that in this species, in analogy with the situation in primates, a number of parallel basal ganglia-thalamocortical circuits exist. Furthermore, data are presented indicating that the projections from particular parts of the amygdala and from individual nuclei of the midline and intralaminar thalamic complex to the prefrontal cortex and the striatum are in register with the arrangements in the parallel circuits. These findings emphasize that the functions of the different subregions of the prefrontal cortex cannot be considered separately but must be viewed as components of the integrative functions of the circuits in which they are involved. PMID- 2094918 TI - Case #6. Mucocele. PMID- 2094921 TI - Steppingstone. PMID- 2094920 TI - Training sessions offer protection. PMID- 2094919 TI - Where does it go? PMID- 2094922 TI - Hygiene critical in Third World. PMID- 2094923 TI - 1989 C. H. McCloy research lecture: health, exercise, and the biomedical impulse, 1870-1914. PMID- 2094924 TI - Relationships between peak torque, peak angular impulse, and average power in the thigh muscles of subjects with knee damage. AB - The purpose of this study was to determine the relationship between the isometric and isokinetic peak torque (PT) (speed of movement 0, 60, and 180 deg/s) and the peak angular impulse (PAI) and average power (AP) of multiple contractions (180 deg/s) of the quadriceps and hamstrings in 29 patients with a chronic, complete deficiency of the medial collateral ligament (MCL) of the knee. At every test speed the Pearson product moment (r) and the Spearman rank (rs) correlation coefficients between the PT and PAI were highly significant for both muscle groups in the uninjured (r = .81-.97, rs = .77-.97) as well as in the MCL deficient (r = .77-.97, rs = .75-.95 knees. The results were the same between the PT and AP (uninjured knee: r = .83-.98, rs = .82-.98; MCL deficient knee: r = .78 .97, rs = .76-.97). In both knees and in both muscle groups the correlation coefficients increased toward the highest speed of the isokinetic movement, obviously because the PAI and AP were registered at that speed. In conclusion, concerning MCL deficient or uninjured knees the PAI or AP analysis may offer little additional information about thigh muscle function to that attained by more simple measurement, the PT analysis. PMID- 2094925 TI - The measurement of physical activity in young children. AB - Two studies were conducted to determine the validity of various measures of physical activity in young children. In Study 1, 21 preschool children were utilized to explore how well measures of children's activity obtained from parents, teachers, and the children predicted observed behavior at school and in the home. Study 2 (n = 51 preschool children) focused on the predictive validity of the Caltrac motion sensor. In both studies, detailed minute-by-minute ratings of children's activity in Study 1 were generally ineffective in predicting observed physical activity. Children's activity preferences, however, were significantly related to the proportion of high intensity physical activity performed. In Study 2, there was a significant relationship (r = .86, p less than .0001) between Caltrac readings and observed physical activity. This correlation was similar for boys and girls, normal and overweight children, and younger and older children. These findings suggest that the Caltrac monitor may provide a valid index of individual differences in physical activity in young children. PMID- 2094926 TI - Establishing reliability of biomechanical data using univariate and multivariate approaches. AB - The purpose of this study was to use generalizability theory with both univariate and multivariate approaches to examine reliability of total body center of mass (CM) values calculated from cinematographical data. Twenty-eight college-aged male volunteers were filmed by a LOCAM camera at 100 fps while performing the basic locomotion skill of walking. Film analysis was conducted on each subject using six frames of film depicting a one-stride walking cycle consisting of right heel strike, right foot flat, left toe-off, left heel strike, left foot flat, and right toe-off. Nineteen segmental endpoints and a reference point were digitized by three experienced plotters. The digitizing sequence was replicated three times by each plotter. A FORTRAN program calculated nine CM values (three plotters by three repetitions) for each subject filmed in each of the six positions of the stride. The x- and y-coordinates of the CM values were the dependent variables analyzed by fully crossed 3-way univariate and multivariate ANOVAs (subjects by plotters by repetitions). All measurement facets were considered to be random. Results indicate that there was very little repetition error but considerable interplotter error for most frames. Phi-coefficients for x- and y-coordinates, separately, fluctuated across frames. The univariate values for the x-coordinates were similar but slightly less than the multivariate values. The Phi-coefficients for Y, however, were considerably lower than the multivariate values. The multivariate Phi-coefficients for generalizing over three plotters and three repetitions ranged from .82 to .90.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094927 TI - One-parameter item response theory models for psychomotor tests involving repeated, independent attempts. AB - Three one-parameter item response theory models are given as viable models that describe the observed score probabilities of an examinee who takes a multiple attempts, single-item test of a psychomotor skill. These models include the Binomial Trials Model, the Poisson Counts Model, and the Inverse Binomial Model. The paper presents these models and offers suggestions for their estimation and subsequent use in the assessment of psychomotor behavior. PMID- 2094928 TI - Specificity and variability of practice. AB - The specificity of learning principle proposes that motor skills are specific and only superficially resemble other similar skills or variations of the same skill. On the other hand, the variability of practice hypothesis derived from schema theory proposes that experiences with task variations are vital to the development of the memories (schemata) responsible for response production and learning. This paper contrasts these two positions in two experiments aimed at determining the influence of providing variable and/or specific acquisition experiences on the retention of a force production task. The results clearly indicated that acquisition practice with variations of the criterion task leads to better retention than practice on the criterion task alone. This finding is contrary to a strict interpretation of the specificity of learning principle and suggests that paradigms investigating schema notions should be expanded to include potential impacts of variability of practice on tasks experienced during acquisition. PMID- 2094929 TI - Age at menarche and selected menstrual characteristics in young Japanese athletes. AB - Ages at menarche and selected menstrual characteristics in 204 nonathletes, 253 high school athletes, 386 college athletes, and 40 young top athletes of Japan were investigated by questionnaire. Data from the questionnaire have confirmed (a) the ascending trend of ages of menarche with advancement of training and competitive level, and (b) the diversity of mean age at menarche by sport in a given level. The menarcheal orders by sport in the literature have been found to be strikingly similar to those found in the present data. We offer the hypothesis that ages at menarche and selected menarcheal characteristics (a) are brought about by selection in the socialization process into sports participation, and (b) reflect the diversity of suitable physiques by sport. Also, the higher the training and competitive level, the more likely the occurrence of menstrual irregularity (cycle length and period duration) and/or dysmenorrhea (backache). PMID- 2094930 TI - Comparison of Harpenden and Lange calipers in predicting body composition. PMID- 2094931 TI - Reliability of muscle mechanical characteristics for isokinetic and isotonic squat and bench press exercise using a multifunction computerized dynamometer. PMID- 2094932 TI - Gold medal volleyball: the training program and physiological profile of the 1984 Olympic champions. PMID- 2094933 TI - A multivariate study of pursuit rotor skill development. PMID- 2094934 TI - Preparatory postural positions and body composition measurement by bioelectrical impedance. PMID- 2094935 TI - Comment on a preliminary comparison of front and back squat exercises (Russell & Phillips, 1989) PMID- 2094936 TI - Reversal of doxorubicin and cisplatin resistance in vivo in murine leukemias by the calcium antagonist RO 11-2933. AB - The ability of RO 11-2933 to modulate in vivo Doxorubicin and Cisplatin antitumor activity has been evaluated in sensitive and resistant P388 and L1210 murine leukemias. A reversal of both Doxorubicin or Cisplatin resistance has been observed when P388/Dx or L1210/CP tumor bearing mice received multiple treatments of the antitumor agent plus 30 mg/Kg of RO 11-2933. No modification of Doxorubicin or Cisplatin effect has been observed in sensitive tumors. The results obtained indicate that RO 11-2933 might represent a promising agent for the reversal of multidrug resistance. PMID- 2094937 TI - Low-dose systemic doxorubicin in combination with regional hepatic hyperthermia. AB - The influence of regional liver hyperthermia in conjunction with systemic doxorubicin administration was examined in a rabbit VX2 tumour model. Hyperthermia was delivered by 2450MHz microwave generator to the exteriorised livers of the rabbits to provide a thermal dose equivalent of 43 degrees C for 30 minutes. Animals receiving doxorubicin infusion were treated with a total of 1.2 mg/kg over a 3 day protocol through an ear vein. Rabbits were divided into 4 groups; a no treatment control, hyperthermia alone, doxorubicin alone and hyperthermia immediately preceded by doxorubicin. The tumour mass, 10 days post treatment was significantly (P less than 0.0001) reduced in all treatment groups. However, the mean tumour mass in the combination treatment group was also significantly lower than both treatments alone (P less than 0.001). This increased response was not accompanied by any signs of increased systemic or local toxicity associated with any treatment. PMID- 2094938 TI - Bepridil enhances adriamycin-induced DNA biosynthesis inhibition in human myeloid leukemia cells. AB - The utilization of drug response modulators, based on their physico-chemical properties to augment the cytotoxic response of anticancer drugs is now gaining importance. We present in this communication, investigations performed to assess the antitumor activity of Adriamycin (ADR), on chronic myeloid leukemia (CML) cells, and the effect of bepridil, a calcium channel blocker on the ADR cytotoxicity. Inhibition of 3H-thymidine incorporation into DNA was used as an index of the cytotoxic effects of drugs when utilised alone or in combination. The combination of bepridil (1 and 5 micrograms/ml) and ADR (5 and 10 micrograms/ml) indicated a significant (P less than 0.001) enhancement in the DNA biosynthesis inhibition in CML cells, as compared to those samples exposed to ADR alone. The observed inhibition of DNA biosynthesis was found to be totally reversible, partially reversible and completely irreversible when the CML cells were exposed to bepridil alone, ADR alone and ADR plus bepridil, respectively. Bepridil was found to be highly lipid soluble at physiological pH, and this property could be responsible for the modulation of the ADR activity observed in this study. Results obtained, though preliminary due to the small sample size, clearly indicate a necessity for a detailed evaluation of bepridil effects, which would lead to higher therapeutic gains in anticancer chemotherapy in the clinic. PMID- 2094939 TI - Free and liposomal doxorubicin treatment of intraperitoneal colon 26 tumor: therapeutic and pharmacologic studies. AB - Intraperitoneal (i.p.) chemotherapy is being investigated as an adjunct to surgery to kill residual cancer cells, inhibit cancer cell seeding, local recurrence, and metastases for ovarian, gastric, and colon cancers. In this report, the therapeutic effects of Doxorubicin (Dox) and liposome-entrapped Dox (Dox-Lip) against i.p. mouse colon 26 (C26) tumor were compared. It was found that Dox-Lip was less toxic than Dox after i.p. administration in non-tumor bearing animals. I.P. Dox and Dox-Lip significantly inhibited the growth of C26 tumor when the treatment was initiated 1 day after tumor cell inoculation, but both administration forms were ineffective against well-established (8-day) tumors. Multiple dose schedules did not improve the therapeutic response. Dox-Lip was not therapeutically superior to Dox at equal doses or at approximately equi toxic doses. In addition, the relative retention of Dox and Dox-Lip in the peritoneal cavity and their plasma pharmacokinetics were investigated. It was found that Dox levels in the peritoneal cavity were maintained for longer periods after i.p. Dox-Lip was administered. However, the results show that maintenance of elevated drug levels in the peritoneal cavity does not necessarily lead to increased therapeutic effects. PMID- 2094940 TI - [Emergency treatment: coronal restoration with pulpal-dentinal protection. Splints]. AB - The authors, explain the need of a pulpo-dentinal protection, and present the way to adopt in case of dental traumas, as well for hard tissues (coronal and radicular) and for non calcified tissues (luxations). This protection allows a cicatrisation of dento-periodontal tissues. PMID- 2094941 TI - [Total luxation]. PMID- 2094942 TI - [Complete luxation with loss of the tooth: an implant case]. AB - The purpose of this article is to report a possible use of dental implants in children. The immediate implantation of an aluminium artificial frialite root, is described in an 8 years old child following the complete avulsion with loss of her center incisor. Osteo integration and the surgical placement technique of the Frialite implant are reviewed. The selection of an implant and of the immediate implantation concept are also discussed in this article. This implant will either become functional as a prosthetic abutment or esthetic by filling the alveolus, as it avoids the formation of a concavity in the edentulous ridge. PMID- 2094943 TI - [Orthodontic effects of tooth injury to the permanent and temporary incisors of children and the adolescent [corrected]. AB - Traumatisms on the deciduous upper incisors could induce orthodontic indirect consequences on the permanent germ, dependent on his growth level and his malleability, dependent on connection between the root of deciduous incisor and the crown of permanent germ and according to the type of traumatism. According to those various data, it should be observed on the permanent incisor: germination of two germs, multiple odontoma, crown dilaceration, severe tipping of the crown with facial angulation, retention of the permanent germ with lack of root resorption of the deciduous teeth or simple cross-bite, without speaking of enamel defect. PMID- 2094944 TI - [Gastric polyps. Experience at the department of endoscopy of the Salvador Zubiran National Institute of Nutrition]. AB - During 1981-1989 we seen 54 patients with gastric polyps in the Instituto Nacional de la Nutricion SZ, Endoscopy Dept., Mexico City. We found 100 polyps among 15,974 upper endoscopy studies (0.33%), being multiple in 22 patients with an overall of 68 polyps. Females had a predominance of 2:1 with prevalence from the 5th to 8th decades. All were asymptomatic in regard to polyps. Its main locations were in antrum (46%) and corpus (39%). They measured an average of 8 mm with a range from 5 to 25. Only three adenomatous polyps shows dysplastic changes, two with moderate dysplasia and one, bigger than 20 mm, had severe dysplasia (carcinoma in situ). Histological findings were: Inflammatory (chronic gastritis) 30%, adenomatous 22%, hyperplastic 17% and hamartomatous 13%. In seven patients we seen recurrence at follow up. PMID- 2094945 TI - [Exercise-induced asthma]. PMID- 2094946 TI - [Treatment of bronchial asthma in winter using controlled-release salbutamol]. AB - This paper presents results about comparative study in winter season, in a statistics design AB and BA on 20 patients that were treated with salbutamol (Group B) and with salbutamol of controlled liberation (Group B) at random. Results showed that patients of Group B had improvement in symptomatology and had less exacerbations than those patients of group A with statistical significance. It was concluded that salbutamol tablets of controlled liberation is a therapeutic method adequate to control chronic phase of asthmatic patients in winter season. PMID- 2094947 TI - [An estimation of the prevalence of hanseniasis by research in non-specific demand for health services]. AB - In view of the importance of knowing the prevalence and incidence rates of a disease to learn about its behavior and control at the collective level, a study was undertaken to determine the occurrence of hanseniasis among the clients of health agencies and to explore the use of this methodology for estimating the epidemiologic "iceberg" of the disease, i.e., the total number of cases including those that are not officially reported. The city of Taubate in the Paraiba Valley, State of S. Paulo, Brazil, was chosen for the study. All clients aged 15 years or older were screened regardless of variables such as sex, age, social condition or marital status. The study was based on what is known about the populational distribution of the disease and the characteristics of health services. In view of the local peculiarities of operationalization (e.g., identity of the different clientele, availability of offices, hours of greatest flux), the sampling process used was simple randomization. The patients with active disease detected, 40 of the 10,013 persons examined, correspond to a prevalence of 3.99/1000, with a confidence interval (at the 5% level of reliability) of 3,365 to 4,625/1000, indicating that the minimum estimated increase of prevalence is of the order of 52% and the maximum estimated increase is of the order of 109%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094948 TI - [Social development and infant mortality, 1977-1986, Cuba. A regional analysis]. AB - In Cuba, the infant mortality rate (IMR) dropped by 65% between 1970 and 1986. The 1986 IMR - 13.6% - has put the country in the lead in Latin American mother and child health care. However, the behavior of the IMR is not homogeneous throughout the country. This paper seeks to identify by multiple regression techniques, those sociodemographic or health care factors which have determined the decline in the IMR and those variables which best explain the inter-regional differences in this indicator. Sociodemographic factors fundamentally explain the evolution of the IMR in Cuba; on the other hand, although in the first instance the proportion of live births of low weight and the crude birth rate explain the inter-regional differences in IMR levels every year, it can be seen that other socioeconomic variables really lie behind these differences. PMID- 2094949 TI - [Maternal perception of dehydration in children with diarrhea. A study on agreement with clinical diagnosis]. AB - The mother's perception of signs and symptoms of dehydration in children under three years of age was studied and compared with the medical classification. The study was carried out in a children's hospital in the city of Rio de Janeiro, among children hospitalized with diarrhoea between January, 1987 and February, 1988. The number of excretions and of vomitings, thirst and condition of eyes constituted the signs and symptoms most frequently reported by mothers. However, they had difficulty in judging the amount of urine, humidity of mouth and tongue and turgidity of the skin. These signs were almost always regarded as normal or, at most, as indicating only slight alteration. Those mothers who tended to underestimate the severity of the dehydration indicated by the physician were of a lower educational level and had more severely undernourished children and greater difficulty of access to the hospital. On the other hand, those who tended to overestimate it belonged to a higher educational level, had better-nourished children, greater ease of access to the hospital and were attended to by a smaller number of health care services before reaching the hospital surveyed. Those who agreed with the medical diagnosis were in an intermediate situation, although they tended to be closer to those who underestimated the gravity of the dehydration. Those mothers whose children had already gone through a dehydration episode did not present a more intense agreement with the physician's diagnosis, thus evidencing that the information afforded at the health care service was either non-existent or inadequate. PMID- 2094950 TI - [Growth and development in the practice of health services. Historical review of the concept of child]. AB - Conditions for the emergence and development of health and social policy programs for children are discussed. The concepts of the child, health and health services prevalent in certain historical periods are expounded, as are the relationships of these proposals to the political and economic interest dominant in each social context, in the light of the social aspect of knowledge. PMID- 2094952 TI - [Present situation of official statistics related to mortality from external causes]. AB - A study was carried out on the basis of research data of the deaths due to all kinds of accidents and violence of 550 children of less than 15 years of age, resident in the municipality of S. Paulo, State of S. Paulo, Brazil, which occurred during 1985. The project sought to correlate the existing data of the files of the Institute of Legal Medicine (IML) with those of SEADE Foundation (official statistics) and then compare them with the investigator opinion (this latter based on all the additional information available) with a view to: analysing the reliability of the official statistics concerning the main cause of death; and discovering the possible deficiency in the transcription of the IML information to the SEADE Foundation in relation to the same cause. The results are as follows: existing IML information stands quite close to the interviewer's opinion (71.54%) when working at the level of the categories of the International Classification of Diseases (ICD-9), reaching 84.77% of agreement when grouping level is considered; in relation to the interviewer's opinion, official statistics proved to be more reliable when analysed at the grouping level than that at the 3rd digit (67.13% and 24.05%, respectively); comparison between IML and SEADE Foundation data shows only 40% of agreement concerning the ICD-9 categories, reaching 75% when grouping data are analysed. These figures corroborate the proposed hypothesis that the IML, though having files with highly detailed information, does not transfer them to the SEADE Foundation, thus diminishing the reliability of the official statistics when the details of each cause of death are considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2094951 TI - Subsequent pregnancies: who has them and who wants them? Observations from an urban center in southern Brazil. AB - Subsequent pregnancies in mothers of a birth cohort from Pelotas, Southern Brazil, were studied in relation to maternal and socio-economic factors. Within about 3 1/2 years of the cohort child's birth, 39% of mothers had experienced at least one further pregnancy. This proportion decreased with increasing maternal age, years of schooling and family income. A U-shaped trend was observed with respect to parity. Mothers who had delivered the cohort child by caesarean section were also less likely to have another pregnancy within that time. Logistic regression analysis showed that each of these factors remained significantly associated with further pregnancies after controlling for the remaining variables. Analysis of the first subsequent pregnancy showed that a high proportion of mothers had not wanted the pregnancy. Unwanted pregnancies were also significantly associated with older women, low educational status, higher parity and low family income. PMID- 2094953 TI - [Identification of the public health nurse within the public health work force in the Regional Health Department-6 of Ribeirao Preto, SP, (Brazil)]. AB - The general purpose of this study was the identification of the nurse within the public health work force in the Regional Health Department of Ribeirao Preto of the State Health Secretariat of S. Paulo. A questionnaire the options of which included: identification, level of training, progress in career, function, future professional expectations and membership of professional associations, was the chief data source. Of the group studies 35 were female, 40% of whom were between 20 and 39 years old, 51.5% were married and 77.2% had been in service for from zero to fifteen years. Regarding the other categories, distribution was as follows: 1 nurse per 13.5 assistants; 1 nurse per 9.1 doctors. Concerning professional training, 71.5% were qualified in Public Health Nursing and 8.6% specialized in Public Health. No career opportunities were available in the nursing profession and their salaries ranged from two to seven minimum salaries, only one receiving ten. All condemned the system of performance assessment. All nurses performed largely administrative services and the inspectors did so for some 65% of their time. Among nursing assistants this percentage rose to 73.3% for those in charge. The nurses were prepared to participate in primary care programmes and 84.3% intended to continue working until retirement. PMID- 2094954 TI - [Demand of community health services in the periphery of a metropolitan area]. AB - The content of 4,319 consultations in primary health care representing 7% of all consultations from March, 1985 to March, 1986 at the Murialdo Health Center, was analyzed. The health center is located in the outskirts of Porto Alegre, RS (Brazil). Woman represented 67% of the total demand. Most consultations were for children under 10 years of age (37%) and woman of childbearing age (21%). The first twenty reasons for the visit corresponded to 63% of the total, and the most common reason for visiting the health center was for renewal of prescriptions and/or ordering medication (9.3%). Of all the diagnoses, the first twenty accounted for 62% of the total number of patients and the most frequent were: hypertension (8.8%), upper respiratory tract infection (7.8%), and immunization (5.5%). Prescription and administration of medication were the most common actions performed. Referrals resulted in 7.3% of the visits. Of these, 5% were sent to other providers within the Murialdo service. Only 0.6% were referred for hospitalization. These findings, combined with others which describe aspects of morbimortality not easily measured in studies of spontaneous demand for medical services, should help in the planning of primary health care services and in the training of health personnel. PMID- 2094955 TI - [Breast-milk substitutes: past and present]. AB - The historical development of industrialized products used as breast-milk, substitutes a process begun in the 18th century, is studied. The marketing strategy currently adopted infant formula companies is stressed and the different commercial practices used in the search for new markets in third world countries are described. A warning is given as to the precise instructions giver for the use of the so-called breast-milk substitutes, and the attention of health professionals and consumer groups is called to the low level of awareness regarding this subject, a factor which led the World Health Organization and United Nations Children's Fund to recommend the preparation of an appropriate marketing code and to its adoption by Brazil. PMID- 2094956 TI - The clinical benefits of ultra-pure replacement factor therapy. Proceedings of a symposium. December 1, 1989, Atlanta, Georgia, in conjunction with the 31st annual meeting of the American Society of Hematology. PMID- 2094959 TI - Emerging roles of social work in perinatal services. AB - Perinatal social work is a recent field of practice with expanding opportunities and responsibilities for social workers in direct practice, research and education. This paper discusses the emergence of high technology in the perinatal field and the specialization of social work knowledge, skills and roles which are developing in tandem with bio-medical advances. The need to reconcile compelling needs for preventive social work practice with those of specialization are examined. PMID- 2094958 TI - Identifying factors in post-operative successful adaptation to pediatric liver transplantation. AB - In order to identify variables contributing to successful adaptation to liver transplantation, 38 families, at least six months post-transplant, were divided according to transplant team members' rating into two groups: those with successful adaptation to transplant and those families at risk for difficulties. Families who had successful follow-up periods tended to be characterized by intact marriages, private insurance coverage, less subjective financial stress, and higher intellectual and developmental functioning in the child. Single-parent families who had no pre-evaluation involvement with liver transplant organizations and had lengthy post-operative hospital stays more frequently had complications post-transplant. Case studies are presented illustrating the application of this information. PMID- 2094957 TI - Clinical experience of a new monoclonal antibody purified factor IX: half-life, recovery, and safety in patients with hemophilia B. AB - Highly purified factor IX, produced by a monoclonal antibody immunoaffinity technique, contains a high concentration of factor IX with negligible amounts of other vitamin K-dependent coagulation factors. When infused in patients with hemophilia B, monoclonal factor IX concentrate yielded a mean half-life of 34.6 +/- 13.1 (+/- SD) hours and in vivo recovery of 0.67 +/- 0.14 U/dL rise per each U/kg of factor IX infused. Unlike prothrombin complex concentrate (PCC) infusion, monoclonal IX infusion was not associated with rises in factors II, VII, and X, but achieved in vivo recovery and half-life at least comparable to PCC. Long-term use of monoclonal IX as a home-care product provided excellent response in the control of bleeding episodes and was equivalent to previous patient experience with PCC. The results indicate that monoclonal IX concentrate raises factor IX levels effectively, while avoiding extraneous thrombogenic components. PMID- 2094960 TI - Health beliefs and practices of foster parents. AB - This study considers how foster parents and social workers contribute to the routine health care of foster children. Health beliefs and practices of foster parents, their relationship to obtaining health care for foster children, and issues of social workers' and foster parents' responsibility for coordinating and obtaining medical care are explored. Suggestions for improved coordination are tendered. PMID- 2094961 TI - Ethics and technological advances: contributions of social work practice. AB - Rapid technological advances in biomedicine have created ethical dilemmas for social workers and other health professionals. This article reviews three areas in which advances have been most dramatic; life support for terminally ill and elderly persons, reproductive technologies and services to severely impaired newborns. It presents principles and processes that can help structure decision making when choices are many and difficult to make. Finally, it suggests ways that social work can use its own technology to help humanize and demystify sophisticated medical technology. PMID- 2094962 TI - The roles of social work in psycho-biological research. AB - Social Workers have an opportunity to utilize their skills in the arena of psychiatric research. Traditional areas of social work functions, including working with patients, families, groups, complicated systems, and interdisciplinary teams, as advocate, therapist, mediator, and manager, are all necessary for the successful implementation of psychiatric research projects with human subjects. The repertoire of social work skills can enhance the successful operation of research involving bio-psycho-pharmacological or neurobiological trials. PMID- 2094963 TI - Enhancing social work influence in the hospital: identifying sources of power. AB - Social workers need to develop interest and skills in hospital politics. Turbulent health care systems, combined with the unique organizational attributes of health care organizations, create environments where political skills are essential to achieve social work goals and objectives. This article identifies sources of social work power within the hospital. Power resides not only in the political acumen of the individual but also in the structural attributes associated with the work group. Discussion focuses on resource control and network centrality as structural sources of social work power. PMID- 2094964 TI - [Current concepts in neuromuscular occlusion]. AB - Occlusal dysfunction is explained on the light of neuromuscular theory. The emphasis is focused on the interaction of occlusion and posture, the way posture modifies occlusion and occlusion modifies posture. The author proposes to include occlusal dysfunction in the wider group of postural dysfunctions defining if this disfunction is originated in occlusal parameters or in postural conditions when the diagnosis is made. PMID- 2094965 TI - Modifications of clinical methodology in Class I restoration with composite resins. AB - This work describes modifications of clinical methodology for the use of composite resins (changes in the isolation of the operating field, in the preparation of the cavities to be occluded and in the way the resin is applied), and relates them to studies of the fine structure of dental enamel and of the adverse side-effects of resins. PMID- 2094967 TI - Incidence of dry mouth complaint in Cork Dental Hospital patient population. AB - The incidence of dry mouth complaint on enquiry was found to be 3.3% on average in a retrospective study of the records of 2500 patients who attended the Cork Dental Hospital. The lowest incidence (1.20--2.66%) was in the youngest age group studied (6--20) years. The incidence increased with age and was substantially higher, reaching 20% in elderly females. In all age groups there was a higher incidence in females. The results are compared with two other studies carried out in Scotland. PMID- 2094966 TI - [Oral presentation of non-Hodgkin's lymphoma. Literature review apropos of a clinical case]. AB - The author makes a review of Non Hodgkin's Lymphoma and Oral Presentations, and includes a case report of the Oral and Maxilo-Facial Surgery of the Snt. Antonio's Hospital--Porto. PMID- 2094968 TI - [Importance of the surgical phase in treatment with osseointegrated implants]. AB - In this article the authors explain extensively the importance of diagnosis before any operation. The authors explain in detail the surgical's phases in general and they go in the depth in many facets of different patients to be treated, differentiating the lower jaw from the upper maxillar and also patients that are totally or partially edentulous. They underline the importance of surgical's templates in order to place fixtures in right places. PMID- 2094969 TI - [Biomaterials in implantology]. PMID- 2094970 TI - [Peritoneal macrophages as a model for the study of the atherogenic potential of the blood serum]. AB - A study was made of the capacity of peritoneal macrophages to demonstrate the atherogenic potential of blood serum. Murine and human macrophages were found to be capable of intracellular accumulation of cholesterol during cultivation with blood sera from patients with coronary atherosclerosis. The data on the capacity to demonstrate blood serum atherogenicity while using peritoneal macrophages do not differ from those obtained previously on the use of smooth muscle cells of the aortal intima and media. The cell culture of the aortal intima and peritoneal macrophages can be used for assessing the atherogenic potential of blood serum. PMID- 2094971 TI - [The long-term physical training of patients with functional class-III stenocardia who have had a myocardial infarct]. AB - Twenty-six patients who suffered myocardial infarction associated with FC III angina pectoris were examined for the effect of physical training on the health status. 25 patients made up the control group. Physical training lasted II months and included remedial exercise, bicycle ergometry training, and graded walking. The central hemodynamics at rest and during exercise was assessed by tetrapolar chest rheography. All reactions in the hemodynamics were analyzed in respect to the status at rest. Ultrasound sectorial scanning was used to study left ventricular contractile function at rest. The patients undergoing training manifested a decrease of angina pectoris manifestations, a considerable rise of work fitness, improvement of the hemodynamic response towards physical exercise, corresponding to 75% of the initial threshold level. In the control group patients, the clinical status, work fitness and the hemodynamic response towards exercise did not undergo any substantial changes. Neither main nor control group demonstrated any appreciable changes on the part of left ventricular contractile function. PMID- 2094972 TI - [The quantitative assessment of the physical work capacity of patients following the surgical correction of heart defects]. PMID- 2094974 TI - [An epidemiological study of chronic bronchitis in an industrial enterprise for preventive purposes]. PMID- 2094973 TI - [The dynamics of the ECG Q-T interval in patients with cervical osteochondrosis undergoing manual therapy]. PMID- 2094975 TI - [Primary subacute infectious endocarditis as a manifestation of surgical sepsis]. PMID- 2094976 TI - [A case of a rare adrenal tumor--myelolipoma]. PMID- 2094977 TI - [Lung and pleural involvement in lymphosarcoma]. AB - The pulmonary-pleural syndrome is often encountered in practice as a manifestation of lymphosarcoma that may be suspected on the basis of "atypical" pneumonia characterized by relapses and tendencies towards bilateral polysegmental lesions with the involvement into the process of the intrathoracic lymph nodes of complicated by hemorrhagic pleurisy, with the presence of pronounced alterations on the part of the blood in the form of anemia and lymphocytosis. Biopsy of an enlarged peripheral lymph node is the only reliable method of verification of lymphosarcoma diagnosis. PMID- 2094978 TI - [The small intestine involvement syndrome syndrome in AIDS]. PMID- 2094979 TI - [Erythropoietin: its biological properties and clinical use]. PMID- 2094981 TI - [The prospects for using fish oil in preventing and treating dyslipoproteinemia and atherosclerosis]. PMID- 2094980 TI - [The debatable aspects of the pathogenesis of nephrotic edema]. PMID- 2094982 TI - [The prognosis of the outcome and the correction of the treatment in bacterial meningitis by using immunological monitoring]. AB - The clinico-etiological characteristics of bacterial meningitides and cellular immunity were studied over time. Measurements were made of the phagocytic index, the phagocytic number, phagocytosis completeness, E-RFC, complementary activity of blood serum (CABS), circulating immune complexes (CIC) and IgA, IgM and IgG. The low phagocytic activity of neutrophils, phagocytosis incompleteness, the high level of CIC, a considerable reduction on CABS were associated with a grave clinical course of bacterial meningitides. In fact, they served as indicators of the necessity of instituting intensive care (hemoperfusion, plasmapheresis, ultraviolet and laser blood radiation, the use of immunomodulators). The combined administration of sodium nucleinate, levamisole and hemodez provided rapid and efficient recovery of the characteristics under study. PMID- 2094984 TI - [The enzymatic antioxidant system of the thrombocytes in meningococcal infection]. AB - A study was made of the time-course of changes in the activity of the enzymic antioxidant system of blood platelets from patients with meningococcemia and meningitis (mixed form) of medium gravity. As a result a steady unbalance in the redox system of glutathione was established: a decrease of glutathione reductase activity and rise of the activity of glutathione peroxidases to hydrogen peroxide and tertiary butyl hydroperoxide until the clinical recovery. The patients with meningococcal meningitis and with the mixed form of medium gravity manifested impairment of the interrelations between superoxide dismutase and glutathione peroxidase to hydrogen peroxide, with that impairment being eliminated by the end of the disease. Potential mechanisms by which the enzymic antioxidant system is impaired in meningococcal infection are discussed. PMID- 2094985 TI - [The chemiluminescence of the polymorphonuclear leukocytes in food poisoning]. AB - Luminol- and lucigenin-dependent chemiluminescence (CL) induced by zymosan, opsonized autoserum was used to study the oxygen-dependent bactericidal system of polymorphonuclear leukocytes (PNL) in patients with food toxico-infections, at different disease periods. Different modifications of CL were established to have analogous dynamics on days 1 and 2 of the disease and differences as to the period of convalescence. A correlation was revealed between the amplitude of CL and the intensity of the intoxication syndrome. The conclusion is made about the role played by granulocytes in the disease pathogenesis. The authors review potential mechanisms of participation of PNL free radicals in the pathophysiological shifts responsible for the development, course and outcome of food toxico-infections. PMID- 2094983 TI - [The functional characteristics of the enzymatic antioxidant system in the erythrocytes and neutrophils of the blood of patients with generalized forms of meningococcal infection]. AB - Patients with meningococcal infection, meningitis and with a mixed form of the disease were demonstrated to have unbalance in the redox system of glutathione during the all disease periods till the clinical recovery. Activation of glutathione peroxidases to hydrogen peroxide and tertiary butyl hydroperoxide in erythrocytes was coupled, during the whole disease, with unbalance of the time course of changes in the interrelated enzymes--superoxide dismutase and glutathione peroxidase to hydrogen peroxide, while in neutrophils, the balance of those enzymes remained unimpaired. Glutathione transferase activity appeared reduced both in erythrocytes and neutrophils. Potential mechanisms by which the redox system of glutathione and superoxide dismutase may be deranged in meningococcal infection are under discussion. PMID- 2094986 TI - [Current problems in the vaccinal prevention of infectious diseases and the approaches to their resolution]. PMID- 2094987 TI - [Errors in performing pathogenetic therapy in acute intestinal infections]. AB - The authors describe the data obtained by them during many years of pathogenetic treatment of patients with acute intestinal infections. Note the main errors made during treatment and giving rise to unfavourable outcomes. Give practical recommendations for carrying out pathogenetic therapy bearing in mind the age associated characteristics and associated diseases. Draw the clinicians' attention to infusion therapy. PMID- 2094988 TI - [The clinico-pathogenetic significance of disorders of the immune status in dysentery]. AB - As many as 256 patients with Flexner's dysentery caused by the same source of infection were examined. It has been established that in patients with a severe and protracted course of the disease, secondary immunodeficiency is formed by the relative hypersuppressor type and the function of phagocytizing macrophages decreases. Patients with the reduced immune characteristics manifest deceleration of convalescence and repeated isolation of Shigella after the antibiotic therapy. It is concluded that the use of immunocorrectors is advisable in a complex of different methods of the treatment for the protracted and severe forms of dysentery. PMID- 2094989 TI - [The role of opisthorchiasis in the development of gastroduodenal pathology in young people. Its prevention and rehabilitation]. AB - A comprehensive examination and follow-up of 400 men aged 18 to 30 years have demonstrated that opisthorchiasis leads sooner or later to functional and morphological alterations in the gastroduodenal system. Their onset and intensity are determined by immunobiological responsiveness of the body and invasion duration. Early diagnosis, multimodality treatment including anthelminthic drugs, and rehabilitation measures enable gastroduodenal pathology to be prevented or reduced. PMID- 2094991 TI - [The results of treating fibrous-cavernous tuberculosis in patients with different genetic markers]. AB - Overall 221 patients with fibrous-cavernous tuberculosis were examined. In patients carrying Hp 2-2 haptoglobin and HLA DR2, the disease runs an unfavourable course more frequently. Among the patients with Hp 2-2, the positive dynamics was attained by the 6th month of the treatment in 44.1%, among those with HLA DR2 in 42.3% of cases while in patients carrying the two genetic markers at a time, in only 32.4% of cases. Patients with Hp 2-2 and HLA DR2 require special attention of the treating physician since the very first day of the disease and use of every possible treatment methods. PMID- 2094990 TI - [Leukocyte intracellular metabolism and phagocytic activity in patients with an erysipelatous inflammation]. AB - A total of 118 patients with erysipelatous inflammation were examined for functional-metabolic activity of leukocytes. The consistent changes in the content of glycogen, cationic protein, in phosphatase and myeloperoxidase activity and in the NBT test of neutrophils--the most important components of the microbicidal system of leukocytes--attest to the status of nonspecific reactivity of the body in erysipelatous inflammation. PMID- 2094993 TI - [The role of different microorganisms and infectious processes in the occurrence and course of bronchial asthma]. AB - The role of infection in bronchial asthma (BA) is unknown. The pathogenesis of BA contributes to the origin of infectious processes induced by different microorganisms. In view of the predominance of associations of viruses and bacteria in the etiology and pathogenesis of acute respiratory infections, it is difficult to define in vivo the share and role of these microorganisms which participate in the origin and enhancement of hypersensitivity, hyperreactivity and alterations in beta-adrenoreactivity. Some factors of bacterial pathogenicity promote BA progress. On contact with basophils and mast cells bacteria (both pathogenic ones and ordinary commensals) are capable of liberating histamine and other mediators during colonization of the bronchial tree and origin other infectious process. This mechanism of mediator liberation may contribute to the transformation of pre-asthma to BA or provoke its exacerbation. PMID- 2094995 TI - [Blood plasma amino acids and total protein, their elimination and catabolism during the hemofiltration of patients with acute kidney failure]. AB - Intermittent hemofiltration (HF) was applied to the treatment of 8 patients (3 men and 5 women) with the grave pattern of acute renal failure (ARF) of prerenal origin. Altogether 23 sessions (from one to six in every patient) were performed with replacement of 44.3 +/- 2.8 1 liquid on the average. Two patients died. Of these, one female patient died from progressive peritonitis and sepsis and the other one from cisplatinum intoxication, bone marrow aplasia and sepsis. The content of blood plasma amino acids (AA), total protein and its fractions was measured before and after HF. Measurements were also made of excretion of those substances with filtrate. Besides, the amount of protein AA catabolized during the procedure was calculated according to the kinetics of urea. The authors hold that ARF-associated changes in the content of AA are primarily determined by adaptive shifts in metabolism. Differences in AA consumption were revealed to depend on the period and quality of adaptation. On the average HF brought about losses of 7.5 g AA and 73.1 g protein with filtrate. At the same time 37.5 g AA underwent oxidation, while urea generation rose 2-fold, amounting to 0.48 mmol/kg bw per hour. It is concluded that in ARF patients undergoing intermittent HF, it is necessary that anabolizing glucose and insulin therapy be applied together with replacement infusion of AA and (or) protein. PMID- 2094994 TI - [The complex assessment of disordered bronchial patency in chronic obstructive lung diseases]. AB - There were 63 patients with infectious-allergic bronchial asthma and 13 patients with chronic obstructive bronchitis. The clinical and bronchoscopic manifestations of the broncho-obstructive syndrome were compared to external respiratory function (ERF) reflecting the status of bronchial patency at different levels of the bronchial tree and the measurement data on the rheological properties of bronchial secretion. A reverse interrelationship was discovered between the intensity of asphyxia attacks and patency of the distal bronchial according to the ERF estimates. A correlation was noted between the magnitude of bronchial secretion viscosity and some characteristics: intensity of asphyxia attacks, dyspnea, number of dry rales; bronchial patency according to the ERF estimates. The values of secretion viscosity turned out to be most closely interrelated with the patency of small bronchi. A correlation was discovered between the bronchoscopic findings and bronchial patency of the proximal bronchi (ERF estimates). It is believed that bronchoscopic examination plays an important part in the diagnosis of obstruction of the bronchi accessible to inspection and has a high information content. Hyperdiscrinism intensity determines in many respects the clinical manifestations of the broncho obstructive syndrome, measurement data on viscosity and adhesion of bronchial secretion can be used for assessing the efficacy of the action on bronchial obstruction at the level of small bronchi. PMID- 2094992 TI - [The oxidative metabolic indices of phagocytizing and immunocompetent cells in patients with pulmonary tuberculosis]. AB - Overall 94 patients with different patterns of pulmonary tuberculosis were examined for glutathione peroxidase (GP), glutathione reductase, glucose 6 phosphate dehydrogenase (G 6-PDH) and superoxide dismutase activity in neutrophils and lymphocytes. Chemiluminescence was used to study the capacity of neutrophils to generate free oxygen forms. Neutrophils showed functional deficiency of GP and G 6-PDH. The decrease of the oxygen-producing capacity of neutrophils, unbalance of glutathione-conjugated enzymes in lymphocytes were revealed either. The role of the alterations enumerated in the reduction of function of phagocytizing and immunocompetent cells in patients with pulmonary tuberculosis is discussed. PMID- 2094997 TI - [Calcium salts retention in the skeletal muscles of patients on hemodialysis]. AB - Deposition of amorphous calcium salts in muscle tissue is not only of pathogenic but also of compensatory adaptive character. This occurs in response to bone exclusion from the system of regulation of calcium homeostasis (aluminum or severe uremic intoxication). Apparently, amorphous depositions of calcium salts may buffer fluctuations in ion concentration. Their accumulation is a marker of the weakening of the cellular mechanisms and enhancement of the physicochemical ones by which calcium homeostasis is maintained. PMID- 2094996 TI - [Changes in the rhythms of urinary sodium, potassium and chlorine excretion in patients with circulatory failure]. AB - Measurements were made of the parameters (period, mesor, amplitude) of the rhythms of sodium, potassium and chlorine excretion with urine in patients with different stages of circulatory failure (CF). It has been shown that revelation of the status of neorhythmostasis is an early and sensitive criterion for estimating functions of electrolyte excretion by the kidneys in different CF stages. Dysrhythmostasis that increases depending on the stage of pathology attains maximum during stage IIB CF. In patients with stage IIB CF, there was an appreciable decrease of chlorine excretion mesor. This indicates that in solving the problem of deviation from normal, the parameters of the rhythm were not equally informative. The period turned out the most sensitive parameter of the rhythm. Determination of the time organization of functions and processes provides an undoubtedly more complete idea of the body on the whole. PMID- 2094998 TI - [Arterial hypertension in senile pyelonephritis: the renal hemodynamics]. AB - Eighteen patients aged 60 to 80 years suffering from chronic pyelonephritis (CPN) and nephrogenous arterial hypertension (AH) were examined for intrarenal hemodynamics: effective renal blood flow (ERBF), glomerular filtration rate (GFR), filtration fraction (FF), renal vascular resistance (R). Renal hemodynamics in patients with senile pyelonephritis and AH was found to be characterized by a decrease of ERBF, GFR, FF, an increase of R (p less than 0.01), with the alterations being related to the AH intensity, mass of the functioning renal parenchyma (for GFR) and partly (for R) to the pyelonephritis and AH standing. R which is dependent on the duration and course (number of exacerbations) of CPN is one of the factors that determine the development and gravity of AH in senile pyelonephritis. PMID- 2094999 TI - [Viral hepatitis in pregnant women--the relationship of the severity of the disease to the etiology of the infection]. AB - The author summarizes the experience of many years (1956-1989) gained with studies into the relationship between the gravity of viral hepatitides in the pregnant and etiology of disease. Virus A hepatitis runs a favourable course in the pregnant, i.e. without severe and fulminant forms. In virus B hepatitis, the pregnant women are threatened with the development of hepatic coma associated with a high maternal lethality. The latter one has noticeably been decreasing over the recent years (from 1.79% in 1956-1965 to 0.29% in 1966-1980 and to 0.21% in 1981-1989, which is not so much related to the perfection of the treatment methods as to the diminution of the share of virus B hepatitis. Virus E hepatitis may be of the greatest mortal danger for mothers in conditions of water epidemic. In that case the lethality among pregnant women may reach 12.1% (in the Turkmenian SSR) and 15.6% (in the Kirghiz SSR). The aggravating influences of virus C and D hepatitides on the pregnancy outcomes and maternal lethality have not been studied much. Estimation of etiological factors in viral hepatitis occurring in the pregnant is an important prerequisite for organization of the rational preventive and treatment measures. PMID- 2095000 TI - [The content of fibronectin, fibrinogen, its degradation products and myoglobin in patients with ischemic heart disease]. AB - ELISA using the test systems and a complex of equipment manufactured by Flow Company was employed to study over time the content of fibronectin, fibrinogen, products of its degradation and myoglobin in 178 patients suffering from coronary heart disease (stable and progressive angina pectoris, acute myocardial infarction). The concentration of myoglobin, fibronectin, fibrinogen and products of its degradation was established to depend on the gravity of coronary heart disease and the tame elapsed since the disease onset. In patients with progressive disease, there was an increased consumption of fibronectin which may be due both to its expenditure during blood coagulation and fulfillment of angioprotective function because of exacerbation of systemic atherosclerosis. PMID- 2095001 TI - [The characteristics of the microcirculatory disorders in rheumatic mitral defects and chronic cor pulmonale]. AB - Patients with rheumatic mitral diseases and chronic cor-pulmonale associated with pulmonary hemodynamic disorders were examined for the intravital status of microcirculation in the bulbar conjunctiva. Systemic derangement of microcirculation was discovered, with all the components (resistive, metabolic, capacitance) being involved. In patients suffering from rheumatic fever, the analogous microcirculatory alterations were revealed in the conjunctiva and in the visceral pleura of pulmonary biopsy specimens. This reflects the generalized character of microcirculatory response under pathological conditions. The significance of microcirculatory disorders in the pathogenesis of arterial pulmonary hypertension, respiratory and heart failure is under discussion. PMID- 2095002 TI - [The sympathetic-adrenal system in mitral heart defects in patients of different ages studied by the use of a specific L-DOPA test]. AB - As many as 59 patients aged 35 to 74 years suffering from mitral valvular disease (MVD) were examined for excretion of dopamine (DA), noradrenaline (NA) and adrenaline, parameters indicating the activity of the sympathoadrenal system. Administration of L-DOPA brought about a significant increase of excretion of all catecholamines in all the patients under 59 years and in those aged 60 to 74 years. In patients with stage I and IIA heart failure, DA excretion rose 50-fold in response to L-DOPA administration, in those with stage IIB and III, 17-fold (p less than 0.001). In patients suffering from MVD, no age-associated differences were revealed in the levels of catecholamines and ICM. In patients suffering from MVD with the predominance of stenosis and in those with stage I and IIA heart failure, background excretion of NA was significantly higher than in patients suffering from MVD with the predominance of heart failure (p less than 0.01). Administration of L-DOPA was followed by an appreciable increment of NA exactly in patients suffering from MVD with the predominance of stenosis (p less than 0.001). In the majority of patients with stage III heart failure refractory to multimodality treatment, the L-DOPA test revealed the smallest increment of DA; its excretion rose only 12-fold. Therefore, the progress of heart failure entails a decrease of the reserve potentialities of the sympathoadrenal system, marked by less output of its mediators. PMID- 2095003 TI - Novel putative promoter/enhancer sequences are shared by the mouse and human perforin (Pfp) genes. AB - This report describes the organization of the mouse pore-forming protein (perforin) gene (Pfp), which is highly analogous to that of the corresponding human gene. Pfp comprises three exons, the first of which consists entirely of 5' non-coding sequence, separated by an intron of 1.94 kb from the two polypeptide coding exons. The promoter region of the gene shows strong similarity to that in humans, with six stretches of high homology noted within 0.7 kb of the mRNA cap site. However, many of the sequences of the human gene with similarity to previously described promoter/enhancer elements are poorly conserved in the mouse, suggesting that these motifs may be of no functional significance, and that control mechanisms for expression of Pfp may be highly specific to killer cells. PMID- 2095004 TI - Rheumatoid arthritis may be primarily associated with HLA-DR4 molecules sharing a particular sequence at residues 67-74. AB - Genomic typing of in vitro amplified DNA with sequence-specific oligonucleotide (SSO) probes was performed for DRB1, DQA1, DQB1, DPA1 and DPB1 alleles in 54 random Norwegian rheumatoid arthritis (RA) patients and 181 healthy controls. DRB1 alleles encoding the serological specificity DR4 were found in 80% of the patients, compared to 34% of the controls (relative risk = 7.9, p less than 0.0001). All DR4-positive RA patients carried either DRB1*0401 (Dw4), 0404 (Dw14), or 0405 (Dw15), while no patients were found to carry DRB1*0402 (Dw10) or 0403 (Dw13). The frequency of the DRB1*0101 allele encoding DR1 was not increased, even among DR4-negative RA patients, and we were unable to detect any sharing of other class II alleles among DR4-negative patients. No contribution of any DQA1, DQB1, DPA1 or DPB1 alleles to RA susceptibility could be detected. The results suggest that in the Norwegian population RA is primarily associated with a shared sequence at residues 67-74 of the DR beta 1 chain, but only when this sequence is expressed on DR4 molecules. PMID- 2095005 TI - Association of Cw11 in Japanese patients with psoriasis vulgaris. PMID- 2095006 TI - Transcranial Doppler sonography: anatomical landmarks and normal velocity values. AB - Until recently, both the diagnosis of intracranial occlusive disease of the large brain arteries, as well as intracranial flow abnormalities due to extracranial arterial lesions, have been a "blind spot" for ultrasound techniques. With the advent of transcranial Doppler sonography (TCD), however, a broad spectrum of potential clinical and scientific applications of TCD to the intracranial vasculature has been advocated. In order to achieve an informative insonation of vessels and a correct interpretation of findings, knowledge of both anatomical landmarks within the skull and flow characteristics of distinct vessel segments are necessary. This paper presents such data elaborated from 64 carotid and 42 vertebral angiograms, 40 contrast-medium enhanced CT scans demonstrating the circle of Willis, 122 normal sagittal MRI scans of the brainstem, 40 cadaver skulls, 38 fresh cadavers, 106 normal volunteers and 59 patients with subclavian steal mechanisms. The main findings were as follows: The inner internal carotid artery bifurcation, the M1-segment of the middle cerebral artery, the C3-segment of the carotid siphon, the vertebral artery junction and the top of the basilar artery were found at insonation depths of 60.4 +/- 7, 40 +/- 8 to 60.4 +/- 7, 62 +/- 4, 84 +/- 8 and 108 +/- 8 mm, respectively. Normal mean flow velocities within the M1-segment, the posterior cerebral artery, the carotid siphon and the basilar trunk were 58 +/- 15.6, 39 +/- 9.9, 47 +/- 13.8 and 41 +/- 10 cm/s, respectively, and revealed a marked decrease with age. Intraindividual side-to side differences were low. Vertebrobasilar data from measurements of neuroradiological material closely met in vivo findings in normals and patients. Criteria for the identification of various vessel segments are provided. On the basis of these findings, a topographical orientation within the skull should be possible in order that beginners commence TCD accurately. Normative velocity data are helpful for differentiating normal and pathological flow conditions at different ages. PMID- 2095007 TI - Fetal Doppler shift waveforms in intrauterine growth retardation: laplace transform analysis technique. AB - An approach to the analysis of fetal blood flow velocity/time waveforms is described using a Doppler shift flowmeter. The waveform shape is described in terms of its Laplace transform. Variations in the value of the dominant coefficient in the Laplace transform in the descending thoracic aorta appear to distinguish growth retarded from normally grown fetuses early in pregnancy. Growth retardation was defined by an index of size specifically aimed at detecting the disproportionately grown fetus. Simpler methods of waveform shape description fail to detect the growth retarded fetus early in the second trimester. PMID- 2095008 TI - Determination of the luminal diameter of the radial artery in man by high frequency ultrasound: a methodological study. AB - The validity and reproducibility of measurements of the luminal diameter of the radial artery in man were investigated with Dermascan A, a 20 MHz ultrasound scanner. The luminal diameter of a reference object, a plastic tube, was measured with ultrasound to be 99.0% of stereomicroscopic measurements. By comparing the diameter of the reference object either filled with water or blood at 37 degrees C, the ultrasound velocity in human blood at 37 degrees C was calculated to be 1605 m/s. The intraobserver repeatability coefficients of in-vivo measurements of the radial artery in man were in the same range, whether measurements were repeated after 30 min (14%) or from day to day (12%). The interobserver repeatability coefficient was acceptable (15%) when the site of measurements was marked, whereas measurements without a mark resulted in a repeatability coefficient of 24%. The intravenous administration of 0.5 mg ergotamine tartrate to 5 subjects caused a decrease in the mean luminal diameter of the radial artery from 2.94 mm to 2.42 mm 1 h after ergotamine (p less than 0.05). This ultrasound method for measurements of the luminal diameter should thus be suitable for investigating the effects of physiological and pharmacological stimuli on the arteries per se. PMID- 2095009 TI - Autocorrelation length of normal and myopathic human myocardium measured by acoustic microscopy: implications for clinical ultrasonic tissue characterization. AB - The pattern of acoustic speckle present in ultrasonic images of tissue may be affected by pathological changes in the tissue. To investigate the possibility for such an effect in dilated cardiomyopathy, we examined acoustic micrographs of frozen sections of normal (autopsy) and myopathic (transplant recipient) human myocardium. The resulting images were digitized, and the major axis autocorrelation length calculated for each image. For the normal specimens (n = 75, four patients), the mean autocorrelation length was 37 +/- 18 microns, with the maximum value of 92 microns. The myopathic specimens (n = 64, four patients) had a mean of 52 +/- 19 microns, with a maximum of 100 microns. We conclude that the changes in structure between normal and myopathic myocardium are significant (p less than 0.001), but on so small a scale in relation to the wave length of clinical ultrasound that there will only be changes in the intensity of the backscattered signal, not the pattern of speckle. PMID- 2095010 TI - The biomechanical effects of low-intensity ultrasound on healing tendons. AB - The effect of low-intensity ultrasound on the healing strength of tendons was studied in experimentally tenotomized, repaired and immobilized right tendo calcaneus (Achilles tendon) of 24 rabbits. Ten tendons were sonicated in continuous waves at a space-averaged intensity of 0.5 W cm-2 for 5 min every day. The remaining 14 tendons were mock-sonicated as controls. After nine consecutive treatments, the tendons were excised under anesthesia and compared for differences in tensile strength, tensile stress and energy absorption capacity. Sonication at 0.5 W cm-2 induced a significant increase in the tensile strength (p less than .02), tensile stress (p less than .005) and energy absorption capacity (p less than .001) of the tendons. These findings suggest that high intensity sonication may not be necessary to augment the healing strength of tendons and that sonication at similarly low intensities may enhance the healing process of surgically repaired human tendo calcaneus. PMID- 2095011 TI - Macrophage responsiveness to therapeutic ultrasound. AB - Macrophages are a source of many important growth factors which can act as wound mediators during tissue repair. The aim of this work was to find out if levels of ultrasound which accelerate repair could stimulate the release of fibroblast mitogenic factors from an established macrophage-like cell line (U937). The U937 cells were exposed in vitro to continuous ultrasound at a space average, temporal average intensity of 0.5 W/cm2 at either 0.75 MHz or 3.0 MHz, for 5 min. The macrophage-conditioned medium was removed either 30 min or 12 h after exposure, and placed on 3T3 fibroblast cultures. Fibroblast proliferation (defined here as increase in cell number) was assessed over a 5-day period. The results showed that 0.75 MHz ultrasound appeared to be effective in liberating preformed fibroblast affecting substances from the U937 cells, possibly by producing permeability changes, whereas 3.0 MHz ultrasound appeared to stimulate the cell's ability to synthesize and secrete fibroblast mitogenic factors. PMID- 2095012 TI - Lung damage from exposure to pulsed ultrasound. AB - Motivated by a recent finding that threshold pressures for hemorrhage in mouse lung exposed to the fields of an electrohydraulic lithotripter were less than 2 MPa, we extended the exposures to pulsed ultrasound. Sharply defined thresholds of the order of 1 MPa were found with 10 microseconds length pulses and roughly twice that value for 1 microsecond pulses. The thresholds at 4 MHz are greater than at 1 MHz. The thresholds are comparable for focused and unfocused fields. As would be expected for a cavitation-like phenomenon, temporal average intensity is a very poor predictor of this effect. In the extreme case, lesions were found at temporal average intensities on the order of 1 mW/cm2. PMID- 2095013 TI - The Doppler family. PMID- 2095014 TI - Bibliography of biomedical ultrasound. No. 92. PMID- 2095015 TI - Members. American Ophthalmological Society. PMID- 2095016 TI - Levator force generation in normal subjects. PMID- 2095017 TI - Colobomatous malformations of the eye. PMID- 2095018 TI - Why retrobulbar anesthesia? PMID- 2095019 TI - Visible light and risk of age-related macular degeneration. AB - Sunlight exposure has been suggested as a cause of AMD. To examine this, we collected detailed histories of ocular sun exposure in 838 watermen who work on the Chesapeake Bay. The presence and severity of AMD was assessed in stereo macular photographs. Macular changes were classified into four grades of increasing severity ranging from the presence of 5 or more drusen (AMD-1) to extensive geographic atrophy or disciform scars (AMD-4). Previously, we found no association between AMD and ocular exposure to either UV-B (290 to 320 nm) or two bands of UV-A (320 to 340 nm and 340 to 400 nm). We have undertaken further analysis to determine whether ocular exposure to violet light (400 to 450 nm), blue light (400 to 500 nm), or all visible light (400 to 700 nm) was associated with AMD. Ocular exposure was estimated using model computations of ambient irradiance and estimates of the ratio of ocular to ambient exposure. Compared to age-matched controls, established cases (AMD-4), but not milder cases, had significantly higher exposure to both blue and visible light over the preceding 20 years (Wilcoxon sign rank test, P = 0.027). There was no difference in exposure at younger ages. These data suggest that high levels of exposure to blue and visible light late in life may be important in causing AMD. PMID- 2095020 TI - Fifteen-year argon laser and xenon photocoagulation visual results of Bascom Palmer Eye Institute's patients participating in the Diabetic Retinopathy Study. PMID- 2095021 TI - The complication of pneumatic retinopexy. AB - There have been 26 published series with a total of 1274 detachments operated with pneumatic retinopexy. Eighty percent were reattached with a single procedure and 98% with reoperations. New breaks occurred in 13% and PVR in 4%. The complications published in 101 papers on pneumatic retinopexy in the last 5 years are analyzed as to frequency, prevention, management, and results. PMID- 2095022 TI - Unusual manifestations of X-linked retinoschisis. PMID- 2095023 TI - Inadequacy of a polyester (Mersilene) suture for the reduction of astigmatism after penetrating keratoplasty. AB - Through two prospective studies, we evaluated the use of polyester (Mersilene) sutures in penetrating keratoplasty. Study 1 was a randomized comparison of combined running and interrupted Mersilene and nylon sutures (n = 45). Study 2 was a case series of single running Mersilene with postoperative adjustment of suture tension to manage astigmatism (n = 23). Study 1 demonstrated that Mersilene interrupted sutures were 5.5 times more likely to have handling-related complications compared to nylon (P = 0.01); in addition, they were 3 times as likely to have tissue-related complications as nylon interrupted sutures (P = 0.16). Study 2 demonstrated a complication rate of 69% when Mersilene was used as a single adjustable running suture. At 6 months postoperatively, the median refractive astigmatism for the adjustable cases was 3.37 D (mean, 4.03 +/- 2.37 D). Eyes in Study 2 with significant suture-related complications were 2.85 times more likely to have greater than 4 D of refractive astigmatism than were eyes without suture-related complications. We concluded that Mersilene is an undesirable suture for use in penetrating keratoplasty. PMID- 2095025 TI - Suture adjustment for postkeratoplasty astigmatism. PMID- 2095026 TI - The American Ophthalmological Society guest lecture. Some issues in graduate medical education. PMID- 2095024 TI - Follow-up of closed-loop anterior chamber intraocular lenses inserted at penetrating keratoplasty. PMID- 2095027 TI - The effects of contact lens wear on the morphology of corneal surface cells in the human. PMID- 2095028 TI - Combined penetrating keratoplasty and posterior chamber intraocular lens implantation in the absence of a lens capsule. PMID- 2095029 TI - Some unusual nonallergic causes of giant papillary conjunctivitis. PMID- 2095030 TI - Ocular findings in a form of retinitis pigmentosa with a rhodopsin gene defect. AB - Ocular findings are presented in 17 unrelated patients with a form of autosomal dominant retinitis pigmentosa and the same C to A transversion in codon 23 of the rhodopsin gene. These patients (mean age, 36.6 years) had, on average, significantly better visual acuity and larger ERG amplitudes than 131 unrelated patients (mean age, 32.1 years) with autosomal dominant retinitis pigmentosa without this mutation. These 17 patients from separate families as well as 11 relatives with the mutation from 4 of these families showed interfamilial and intrafamilial variability with respect to severity of their ocular disease. This clinical heterogeneity among patients with the same mutation, with older patients sometimes showing less loss of visual function and less intraretinal bone spicule pigment than younger patients, suggests that some factor other than the gene defect itself is involved in the expression of this condition. This form of retinitis pigmentosa can now be detected by testing leukocyte DNA from peripheral blood. Patients so identified should have an ocular examination to determine the extent of their disease in view of the clinical heterogeneity that exists among patients with this mutation. Some mechanisms by which this mutation in the rhodopsin gene could lead to photoreceptor cell death are discussed. Opportunities for future clinical and laboratory research in search of possible treatments are considered. PMID- 2095031 TI - Ophthalmologic complications of meningomyelocele: a longitudinal study. AB - Patients with spina bifida have multiple ophthalmologic problems, many of which are preventable. Most of the problems are related to the hydrocephalus, which is caused by the coexisting Arnold-Chiari malformation. When patients are treated for hydrocephalus, and comprehensive eye care is available, 94% of the patients will have 6/12 visual acuity or better. Strabismus is common but it responds well to medical and surgical treatment. Children with spina bifida should have frequent examinations by an ophthalmologist who is familiar with the diagnosis and management of the defects recorded in this study. PMID- 2095032 TI - An immunopathologic study of retinoblastoma protein. AB - We investigated the immunoreactivity of the retinoblastoma protein in eight retinoblastoma tumors of different stages of differentiation. All undifferentiated tumor cells failed to show immunoreactivity. In one patient, who had a family history of retinoblastoma and had been treated by radiation, the tumor had a large area of undifferentiated cells and small independent retinocytomas. The tumor cells in the retinocytoma and the cone cells in the adjacent retina, but not the undifferentiated tumor cells, showed positive staining with two anti-Rb antibodies. The immunoreactivity may be related to radiation or differentiation of retinoblastoma and cone cells. PMID- 2095035 TI - Ocular hydrofluoric acid burns: animal model, mechanism of injury and therapy. AB - A series of ocular HF burns was produced in rabbits in order to clarify the nature of the injury and to provide a description of the animal model. Burned eyes were evaluated clinically and allowed to progress for up to 65 days before histologic examination. The mechanism of HF toxicity was investigated through the study of burns produced by chemicals chosen to mimic its pH effects, osmotic effects, and effects of the free fluoride ion alone. The severe progressive caustic effect of HF on the eyes was found to depend on the combination of pH and the toxic effects of the free fluoride ion, together causing extensive dose related damage to superficial and deep structures of the eye. Mild burns caused reversible ocular injury; whereas more severe burns lead to corneal stromal scarring, vascularization, edema, formation of calcific band keratopathy plus iris and ciliary body fibrosis. An investigation was made of potential treatments for experimental ocular HF burns in rabbits. Topical ointments containing MgO or MgSO4 and irrigations with or subconjunctival injections of H2O or solutions containing NaCl, MgCl2, CaCl2, LaCl3, hyamine, zephiran, calcium gluconate or a mixture of divalent metal ions were tested for toxicity and for therapeutic value in ocular HF burns. Immediate single irrigation with H2O, NaCl or MgCl2 solution was most effective. Other therapeutic agents commonly used in HF skin burn therapy were either too toxic in normal eyes or caused additive damage to burned eyes. PMID- 2095033 TI - Parasympathetic denervation of the ciliary muscle following retinal photocoagulation. AB - Cynomolgus monkeys underwent unilateral PRP with xenon arc or argon or krypton laser light, employing burn intensity, size, spacing, and topography analogous to standard clinical (eg, Diabetic Retinopathy Study) treatment. Shortly thereafter, accommodative responsiveness to topical eserine and electrical stimulation of the EWN was diminished, accommodative responsiveness to systemic pilocarpine was enhanced, and the number of muscarinic receptors in the ciliary muscle was reduced in the PRP-treated eyes compared to the contralateral controls. In most instances, these parameters returned to normal over 6 to 12 weeks and the abnormalities could be induced again by another round of PRP. However, in some PRP-treated eyes, accommodative responsiveness to EWN stimulation and topical eserine remained subnormal permanently (greater than 1 year). Light and electron microscopy of the ciliary muscle and choroid confirmed the early interruption and degeneration and the subsequent regeneration of the intraocular parasympathetic nerves following PRP. These findings are similar to those seen after surgical removal of the ciliary ganglion and posterior ciliary nerves, and indicate that PRP produces an intraocular parasympathetic denervation of the ciliary muscle. This phenomenon may explain the loss of voluntary accommodation which can follow PRP in prepresbyopic humans. Three cynomolgus monkeys underwent nasal and temporal HRMP in one eye with the argon laser. One to four weeks later, accommodative responses to IM pilocarpine, topical eserine, and electric stimulation of the EWN did not differ markedly in the treated and control eyes. Five weeks after HRMP, posterior PRP was performed in the same eye, sparing the previously treated areas. One to four weeks later, accommodative responses in the PRP-treated eyes were clearly subsensitive to central electrical stimulation, but supersensitive to IM pilocarpine, compared to the contralateral controls. These findings indicate that extensive parasympathetic denervation of the ciliary muscle occurs following PRP but not following HRMP. Consequently, we infer that parasympathetic motor nerve fibers to the ciliary muscle do not travel preferentially with the LPCN, but rather travel primarily if not exclusively with the more numerous SPCN. If the monkey and the human are comparable, sparing the horizontal retinal meridians during clinical PRP so as not to disturb the LPCN will probably not help to preserve ciliary muscle function and accommodation. PMID- 2095034 TI - Ocular toxoplasmosis in AIDS patients. AB - We describe 16 cases of ocular and, in some patients, associated CNS toxoplasmosis in AIDS patients. T gondii is commonly associated with infection in the immunocompromised host. The lesions are most often seen in the CNS and eyes; involvement in the brain, heart, lung, liver, spleen, and lymph nodes may be observed. CNS involvement by toxoplasmosis may be an initial manifestation of AIDS and may be associated with discrete or diffuse lesions. CT scan and MR imaging may demonstrate a multitude of lesions often displaying the characteristic ring-shaped enhancement after contrast injection. Ocular involvement by toxoplasmosis, though less common than CNS involvement, is characterized by several features. These may be manifested as single or multifocal retinal lesions in one or both eyes or massive areas of retinal necrosis. Invariably these lesions are unassociated with a pre-existing retinochoroidal scar suggesting that the lesions are a manifestation of acquired rather than congenital disease. Presence of IgM antibodies may support this observation although antibody levels in AIDS patients may not reflect the magnitude of disease. Vitreous reaction is often minimal. Anterior uveitis has been reported in one case. Treatment of the ocular infection with pyrimethamine, clindamycin and sulfadiazine is effective in over 75% of patients. Once resolution of the ocular infection is observed, maintenance therapy is continued as relapses occur in the absence of treatment. Corticosteroid treatment is unnecessary and its use has been associated with the development of CMV retinitis. Other retinal infections in AIDS patients which should be considered in the differential diagnosis include CMV, herpetic-associated ARN and syphilis. Concomitant CMV and toxoplasmosis in the same eye have been seen. PMID- 2095036 TI - Orally administered antifungal therapy for experimental keratomycosis. AB - Fluconazole, an experimental azole antifungal agent with good tissue penetration following oral administration, offers the possibility of a new approach to the treatment of keratomycosis. Its efficacy as an orally administered agent was investigated in two models of experimental fungal infection in Dutch-belted rabbits. The study proceeded in three stages. In the first, a model of keratitis due to Aspergillus fumigatus was developed, the suitability of quantitative isolate recovery techniques for the evaluation of the disease caused by this organism was confirmed, and the correlation between the severity of clinical disease scored nonparametrically and the isolate recovery rate was established. The model was found to be most useful for study during the first 5 days of infection. The natural course of experimental Candida alibcans keratitis was evaluated and, on the basis of quantitative isolate recovery techniques, this model was found to be appropriate for studies lasting up to 1 week. In the second stage, corneal uptake following oral administration of fluconazole was studied in Dutch-belted rabbits. The drug was found to readily penetrate the cornea in amounts that correlated with serum levels (R = 0.89). Eight hours following a single 20 mg/kg dose, the corneal level was 7.4 mg/gm, almost double the amount when a 10 mg/kg dose was administered. When given in a twice daily divided dose, fluconazole accumulated steadily in the corneas over a period of 5 days. The presence of inflammation induced by fungal infection did not influence corneal uptake. In the final stage, the efficacy of orally administered fluconazole in the treatment of keratomycosis was evaluated. Overall, a significant therapeutic effect was observed with both infections. Treatment of the animals with oral fluconazole for 1 day prior to inoculation with Candida albicans led to a significant decrease in isolate recovery 1 day later (P = 0.01). However, when treatment was continued for 5 days following inoculation, no additive effect of pretreatment was noted. Pretreatment for 1 day followed by 5 days postinoculation treatment led to a significant decrease in clinical disease (P less than 0.05) and isolate recovery (P = 0.05). A beneficial effect of pretreatment compared to treatment begun 1 day postinoculation, as measured by a reduction in clinical severity and isolate recovery, was also noted. On the basis of these short-term therapeutic studies and the excellent corneal penetration of fluconazole, further investigation of oral therapy of keratomycosis appears warranted. PMID- 2095038 TI - Stress, health and performance in university students. AB - The hypothesis tested was that cognitive factors in the generation of stress, namely perceived coping incapacity (PCI), relate to the extent of psychosomatic ailments. We developed a new scale, CAST (Cognitive Appraisal Stress Test), with a 10 point self-rating of PCI using 16 questions on different aspects of perceived demands versus perceived capabilities. For the assessment of ailments relevant to stress we constructed a scale (PSYSOM) based on a translation of the Scheuch-Vogel symptom list (developed in the GDR from self-report of teachers who could not work as a result of work stress). A special scoring system combined duration, intensity and frequency of 30 symptoms and provided normalisation of distributions. The scales were administered on separate days to 75 female students in their second year (working to obtain admission to an honours degree course). The hypothesis was strongly supported, since the overall scale of PSYSOM correlated with CAST: r = 0.42, p less than .001. The physiologically defined subscale of 'skeletal muscle tension' correlated r = 0.65 with CAST. Subsequently CAST and PSYSOM have been shortened and factor analysed to give, in each case, a general principal component scale and several identifiable varimax subscales. Research using these scales on employees has now provided cross-validation of the first findings reported here. PMID- 2095037 TI - Invasive diagnostic techniques for uveitis and simulating conditions. PMID- 2095039 TI - [Popular appeal of physical grooming and warning against unhealthy cosmetics at the end of the 18th century]. AB - The instruction to preservation of health especially the popularization of the personal hygiene are demanded a serious place from the medicine in the Age of Englightment. In reference to the salubrious influence of the bath and the warning against the use of unhealthy, metallic make-ups the purposive efforts of the physicians are illustrated. PMID- 2095040 TI - [Jewish dietary laws and health education]. AB - We divide the statute of foods in the real food-statute and in the rules about the cooking. Particularly the food-statute, we find in the bible (Leviticus chapter 11 and Deuteronomium chapter 14), demonstrated education of health already, in the antiquity. Essentially the jewish food-laws instruct us in the severe training of temperance and discipline. But that system of education teach men also how they reduce the fat of the animals, which are permitted to eat. Likewise the jewish rules refer to the importance of temperance of alcoholic drinks. The empiric knowledge of reduction and selection of animal food effect a theoretic basis leading to the prophylactic and to the preventive of civilization disease and of cancer development. PMID- 2095041 TI - [Standards for infant clothing]. AB - The presence of clothing for infants does not reflect in quality and quantity the actual situation of medical knowledge. Economical conditions are not responsible for that fact, but especially uninformation of industry and physicians, too. Our contribution should inform doctors, especially from child welfare centres, about clothing to infants. Recommendations were given to a more proper clothing of infants. PMID- 2095042 TI - [Alimentary intake of fluorides of artificially fed infants and effect on enamel tissue]. AB - The dietary daily intake of fluorides in the first six months of lifetime has to be taken into special consideration. The slightly toxicological permissible limits of the fluorides can cause mottled enamels. The safe amount of the dietary daily intake for babies ranged up to 0.5 mg. By use of the food-stuff "MANASAN" prepared with fluoridated drinking water the daily intake increased up to 1.01 mg F-. In 150 7-8-years old children which in the first 4 month of lifetime got "MANASAN" prepared with fluoridated drinking water we found in 40% of the children mottled enamels, the fluorosis index scores (defined by DEAN) 0.4 respectively. The caries prevalence was by 0.85 DMF surfacer index. PMID- 2095043 TI - [Effect of smoking on immunologic parameters]. AB - Non-specific immunological parameters were analysed in dependence of cigarette smoking. Although the serum protein levels were in the normal range, it was remarkable to find some differences between non-smokers, ex-smokers and (heavy) smokers. These differences are especially distinct in the mean levels of IgE, alpha 1 PI and ceruloplasmin. PMID- 2095044 TI - [Lead pollution of work sites in auto body repair shops]. AB - Because of the lead in street dirt and in varnishes of cars it is possible that welders in carriagebody repairs get an unnormal lead exposure. We studied the results of measurements of welddust and their lead concentrations in connection with biological monitoring for lead exposure of the welders. Seperately high lead concentrations in the air of the working zone were obtained indicated through blood lead levels higher than normal value. However the parameter for lead effect erythrocyte protoporphyrin kept normal. PMID- 2095046 TI - [Assessment of health status and current life style of patients with malignant neoplasms]. AB - A review is given on the results of a study investigating the state of health and the psycho-social situation of 211 patients who underwent follow-up for malign neoplasm in the oncological Health Center of Magdeburg. In the course of a conversation the patients were questioned about social and other factors specific for their disease. For evaluating the psychic situation the questionnaire of Hock and Hess was used. The results of the study allowed to conclude that more than 50% of the patients showed psychoreactive disorders. Depending from age and sex as well as the diagnosis marked differences concerning the frequences of psychic peculiarities and the evaluation of the state of health were revealed. The results demonstrate that in addition to specific oncological knowledge the consideration of social and psychic factors is necessary for an optimum follow-up in order to recognize and prevent disorders in this field. PMID- 2095045 TI - [Ultraviolet exposure in the environment of welding work sites]. AB - It has been checked if the "limits of the acceptable doses of ultraviolet radiation of monochromatic radiation at the workplace" (NIOSH-standard of USA) are adhered to in the vicinity of welders' work stations in a factory hall. For recording of UV-doses polysulphon films have been used. According to these investigations non-welders are exposed to doses of UV-radiation which exceed the limits recommended by about eight times. Clinical examinations of these persons showed chronic damage of the external parts of the eyes in a higher percentage than in a control group. It is pointed to the necessity of taking protective measures to shield persons working in the vicinity of welding job sites from ultraviolet radiation. PMID- 2095047 TI - [Exercising care in filling out death certificates]. AB - Death certificates of 1,432 dead persons being older than 1 year of the urban district of Gera (1987) were evaluated. 72.3% of the death certificates showed one or more mistakes. The average number of the mistakes was 1.8. The most numerous formal mistakes and such with regard to the contents were analyzed as well as conclusions were drawn for the further qualification of the coroner physicians and the improvement of filing in the death certificates. PMID- 2095048 TI - [Experiences in incidence monitoring and control of the Pharaoh ant in a health resort]. AB - Today Monomorium pharaonis still represents a threat of the hygiene regime in the objects of Public Health and Welfare, particularly for the asepsis and the "Black White-Separation". The experiences collected throughout a successful rub out by the preparate "Lafarex N 87" in a health-resort are presented. The necessity of cooperation of all concerned persons (owners, pest control enterprises and Public Hygiene Service) are emphasized. PMID- 2095049 TI - [Control of the Pharaoh's ant with borax bait formulations]. AB - Results are given for the experimental control of Pharaoh ants, Monomorium pharaonis L., with persistent borax baits in the laboratory and the field. DYBH bait formulations with about 17 per cent borax are very attractive and have a good effectivity. In 5 different objects infested with this ant eradication was proved to be possible with this experimental formulations. The progress of eradication depends essentially on the good organisational preparation of control measures. PMID- 2095050 TI - [Examples for using capillary gas chromatography with wide bore columns in occupational health]. AB - Wide bore capillary columns (0.4-0.75 mm ID) can be easily and inexpensively installed in packed column GCs. The analytical advantages cause an expanding market for such capillaries and interconverting hardware kits. It is illustrated with some examples that often individual exposition levels can be determined exactly only by using capillary columns: ethylbenzene may be separated from the C8-isomers also in complex mixtures, the marker PBN for rubber smoke expositions can be determined with 30 min sampling time, the detection sensitivity of the FID is sufficient also for chlorinated pesticides and the analyses of high-boiling compounds profit by the high phase ratio of wide bore capillary columns. A single capillary column substitutes a variety of different packed columns, so saving time and money and protecting the analyst from failures and frustrating compromises. PMID- 2095051 TI - [Congress of the European Union of School and University Health and Medicine (EUSUHM), Paris 18-21 September 1989]. PMID- 2095052 TI - [Pathobiochemistry: what can it do, what does it want to do?]. PMID- 2095053 TI - [Ten years of pathobiochemistry in Jena]. PMID- 2095054 TI - [The effect of vitamin E on the survival rate and biochemical parameters such as isocitrate dehydrogenase, lactate and selected peptidases and proteases during endotoxic shock in the rat]. AB - Protective effect of the investigated alpha-tocopherol solution regarding survival and changes of several biochemical parameters in rat endotoxin shock could already be demonstrated after application of the solvent (special oil HCO 60) alone. An additional effect of Vitamin E was observed only in DP IV activity and leukocyte counts. PMID- 2095055 TI - [Classification of hyperthyreosis using enzyme immunoassays for the detection of membrane and thyroglobulin antibodies]. AB - Clinical signs and the determination of thyroid autoantibodies are usually used for the classification of hyperthyroidism. We examined the usefulness of two ELISA for the determination of membrane and thyroglobulin autoantibodies. 117 patients with Graves' disease, 53 patients with toxic goitre and 47 patients with unclear hyperthyroidism were inspected. The best classification into immunogenic and nonimmunogenic hyperthyroidism were achieved with the membrane antibodies at a borderline titre of greater than 1:400. The thyroglobulin antibodies were also useful and increased the security of the classification. We conclude that both tests are suitable for the classification of patients with hyperthyroidism and should be applied to the first diagnostic step in the immunological diagnostic of the thyroid. PMID- 2095056 TI - [The significance of the determination of catecholamines and their metabolites in neuroblastomas]. AB - A method for the determination of catecholamines and their metabolites in the urine was established. The specimens were previously cleaned by ion exchangers and the components were separated by a 'reversed phase' ionic pair chromatography, determined by an electrochemical 'wall-jet'-detector. This method was applied in order to find a diagnostic marker in case of neuroblastoma diseases. In 85 per cent of the patients (n = 13) we stated an increased ejection of dopamine. PMID- 2095057 TI - [Diagnostic importance of HDL cholesterol determination]. AB - The present paper describes the sensitivity to quantification of changes of HDL cholesterol in serum by two different precipitation and analytical techniques during the treatment of patients. After the precipitation of VLDL and LDL by phosphotungstic acid/magnesium chloride the chemical determination of HDL cholesterol in serum with the Liebermann-Burchard reaction yields different results in comparison to enzymatic HDL-cholesterol determined in serum supernatant after the precipitation by polyethylene glycol 20.000. Correlation analyses of apolipoprotein A-I with enzymatic HDL-, HDL2-, HDL3-cholesterol or electrophoretic alpha-cholesterol demonstrate that the therapeutically induced changes (by training and diet) of lipid composition are more correctly reflected by the enzymatic determination of HDL-cholesterol after serum precipitation by polyethylene glycol. PMID- 2095058 TI - [The fructosamine test for the determination of nonenzymatic glycosylated serum proteins. A critical inspection of the method]. AB - A modification of the original method of R.A. Johnson et al. for nonenzymatically glycated serum proteins (fructosamine test) is described. Problems of performance and optimization of the method as well as of calibration and the influence of protein composition on the results are discussed. Measuring is manually performed after a 8 min preincubation interval over a 1 min's period using the spectrophotometer "Spekol 220". Interserial precision was 3.2%. First clinical results demonstrate the possibility to assess glycemic control in type 1 diabetic patients over a integrated time interval. PMID- 2095059 TI - [Determination of glycosylated hemoglobin using affinity chromatography. A comparison of methods]. AB - The determination of glycated hemoglobin is used to judge the quality of adjustment in diabetic diagnostics as this value best represents the mean concentration of blood glucose of recent weeks. At the moment several methods for the determination of glycated hemoglobin are available. A new method is the microcolumn affinity chromatography which proved to be very practicable in our investigations. This paper presents results concerning precision, correlations with other methods, possible interferences and concordance. PMID- 2095060 TI - [The direct detection of volatile fatty acids by gas chromatography in microbiological diagnosis]. AB - The gas chromatographic analysis of volatile fatty acids (VFA) is of great significance in the diagnosis of anaerobes and anaerobic infections, respectively. The ether extraction commonly used for this purpose is relatively consuming in time and material. In this relation, the presented method of detection of VFA in the aqueous phase directly shows essential simplifications but has a lower sensitivity. Therefore, this method cannot replace the ether extraction to investigate broth cultures of anaerobes for taxonomical purposes. But it enables the determination of VFA with sufficient sensitivity in clinical materials of patients. Herewith, the detection of acetic acid only indicates an infection without anaerobes if the concentration is higher than 20 mg/100 ml. On the contrary, a high correlation exists between the detection of n-butyric acid as well as isovaleric acid and the cultural isolation of anaerobic microorganisms. PMID- 2095062 TI - [A colorimetric method for the determination of nitrate in urine]. PMID- 2095061 TI - [Turbidimetric determination of C-reactive protein]. PMID- 2095063 TI - [Optimization of isoelectric focusing by stabilization of output and volt-hour integration]. PMID- 2095064 TI - [Cutting equipment for glass microelectrodes]. PMID- 2095065 TI - Case report. Occlusal and facial anomaly. AB - The following case report is an example of a team of dentists correcting a pronounced occlusal and facial anomaly. A primary care dentist, endodontist, orthodontist, and oral/maxillofacial surgeon all contributed to the successful outcome. As the technological resources available to dentists increase, teamwork between generalists and specialists will become essential for comprehensive restoration to excellent health, function, and esthetics. PMID- 2095067 TI - Patients rights and communication. PMID- 2095066 TI - Fronto-temporal lobe abscess following periodontal recall: discussion for antibiotic prophylaxis. PMID- 2095068 TI - The health care crisis and tort reform. PMID- 2095069 TI - [University examination the only right way in Iceland]. PMID- 2095070 TI - [Mostly old news in first laboratory exhibit]. PMID- 2095071 TI - [Hospital in Ystad causes revolution. Interview by Elisabet Forslind]. PMID- 2095072 TI - [In Aino's ward comprehensive care is put to the test. Interview by Elisabet Forslind]. PMID- 2095074 TI - [Doctor reads detective story: digitalis in the spinach? It won't be enough to take someone's life. Interview by Tord Ajanki]. PMID- 2095075 TI - [Profile of Solweig Bergheden. Interview by Pelle Olsson]. PMID- 2095073 TI - [Uddevalla: when SHSTF protested the ward supervisor temporarily became administrator]. PMID- 2095076 TI - [Leadership position is not just a question of prestige!]. PMID- 2095077 TI - [Only those who burn can be burnt-out]. PMID- 2095078 TI - [Danish donors register]. PMID- 2095079 TI - [In spite of prison and torture Miriam wants to return. Interview by Jan Thomasson]. PMID- 2095080 TI - [Health economics--stopgap measures are no decisions. Interview by Kaj Nyman]. PMID- 2095081 TI - [The Red Cross collects and sorts--it is not nice to send trash to other countries]. PMID- 2095082 TI - [Anki gave up acute care to get perspective. Interview by Carina Roxstrom]. PMID- 2095083 TI - [Amalgam--ever more dentists think it should be limited]. PMID- 2095084 TI - [Worthwhile to know. New technical aids in neonatal care. Clothing for premature infants]. PMID- 2095085 TI - [Homeopathy--200 years of medicine with a million patient visits per year]. PMID- 2095086 TI - [Computer terminal screens--difficult to understand in spite of symptoms]. PMID- 2095087 TI - [Courage to Live. Thoughts after a time of illness]. PMID- 2095089 TI - ["The profession is not the cause of the crisis"]. PMID- 2095088 TI - [Richard Larsson wrote Courage to Live. Bookseller started a new life in the health service. Interview by Christina Mork]. PMID- 2095090 TI - [Prevention is more profitable than therapy. Interview by Kaj Nyman]. PMID- 2095091 TI - [Inger Ohlsson on priority setting: futile belief in endless resources. Interview by Kaj Nyman]. PMID- 2095092 TI - [Crisis meeting in Goteborg supports the rebels]. PMID- 2095093 TI - [Crisis package]. PMID- 2095094 TI - [You have to be a manager for 100 percent. Interview by Kaj Nyman]. PMID- 2095095 TI - [Quite simply, it was nice to have power. Interview by Kaj Nyman]. PMID- 2095096 TI - [Berit looks after finds from the bottom of the ocean. Interview by Torsten Arpi]. PMID- 2095097 TI - [Value of laboratory tests and echography in the diagnosis of biliary disease in the initial phase of acute pancreatitis]. AB - The aim of this study was to investigate the usefulness of serum bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (APh) and real time ultrasonography (US) in distinguishing between gallstone and non gallstone related acute pancreatitis (A.P.). The second aim was to evaluate whether or nor there was biliary tract hypertension. Both aims were designed in order to evaluate them in the early stage of A.P. Two Groups of patients were studied. Group 1--gallstone related A.P., 63 pts. Group 2--Non gallstone related A.P. 21 pts. Fifty nine (93.6%) of Group 1 and 11 (52.3%) of Group 2 had surgical confirmation. In the other, the diagnosis was based on US and C.T. Blood samples were taken during the three days after admission for biochemical test and US was performed within the same period. Statistical evaluation and Student's t test were used. Biochemical test: when the cut off level was expressed by the upper limit of normal (ULN), the highest diagnostic sensibility was (table 1): ALT 85.7%, APH 80.9%. AST 71%, bilirubin 65%. When the cut off level was chosen at twice the ULN (Table 1), the sensibility was: ALT 61.9%, bilirubin and AST 47%, APh 30%, Group 2 (Table 2) values higher than the ULN were: AST 42.8%, bilirubin 33%, ALT 19%, APh 14.2%. The differences between the two Groups were statistically significant: APh and bilirubin P less than 0.001, ALT less than 0.05 m AST, NS. Ultrasonography: Group 1: gallstones were detected in 96.6% (58/60). Biliary tree was not visualized in 10 (15.8%), diagnosed as normal in 38 (60.3%) and pathologic (dilatation and/or lithiasis) in 15 (23.8%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095098 TI - [Evaluation of the usefulness of the physico-chemical study of ascitic fluid in patients with chronic hepatopathies, neoplasms and spontaneous peritonitis]. AB - In order to separate malignancy from chronic liver disease, the ascitic fluid (AF) of 45 in-patients was studied prospectively. Protein, cholesterol, triglycerides, LDH and glucose concentrations were determined in AF. Ascites/Serum (A/S) protein and LDH ratios were also established. Spontaneous bacterial peritonitis (SBP) incidence was studied in the cirrhotic group performing the pH, PMN count and culture of the AF. The 45 patients were classified in three groups: 29 with chronic liver disease, 10 with malignancy and 6 with miscellaneous pathology. Af protein concentration, its A/S ratio and AF cholesterol concentration were statistically significant (p less than 0.001) to differentiate malignancy from chronic liver disease. However, the AF glucose, triglycerides and LDH concentrations and the A/S LSH ratio were not useful in the differential diagnosis. The SBP incidence was 13%, its mortality rate 75% and the cultures were positive only in 25%. PMID- 2095099 TI - Eradication of Campylobacter pylori and recurrence of duodenal ulcer. A six-month follow-up study. AB - Fifty-four patients were studied, 41 men and 13 woman, aged 26-76 years, suffering from duodenal ulcer that healed 4-8 weeks after colloidal bismuth subcitrate therapy (360 mgr twice a day). All patients underwent endoscopy before treatment, 4-8 weeks and 6 months later. Biopsy was taken for campylobacter pylori (C.P.) detection by urease test. All patients were C.P. positive initially. The organisms were eradicated in 36/54 patients (67%) at the end of therapy. Ulcer healing was obtained after 8 weeks in 45/54 patients (83%). They were re-examined 6 months later or sooner if symptoms had recurred. Twenty seven (66%) were then C.P. negative and 14 were C.P. positive. Ulcer recurrence was observed in 15/41 patients (37%) whose ulcer had previously cured. All patients with recurrence were C.P. positive. There was a statistically significant positive correlation between persistence of C.P. and ulcer recurrence rate (p less than 0.001). It is concluded: a) that eradication of C.P. in duodenal ulcer patients has no influence on ulcer healing. b) Duodenal ulcer recurrence is correlated with persistence of C.P. PMID- 2095100 TI - [Value of compression and change of posture of patients in the gastroduodenal double contrast technique]. AB - The authors perform the upper gastrointestinal examination in order to demonstrate lesions that would not be seen by other radiologic techniques. Due to the progress of Endoscopy in the last years, it is necessary a detailed radiologic examination to reach the diagnostic possibilities that the former did. A good help to do that is the compression in prone dedecubitus with inflatable balloon and the patient's mobilization under radioscopic control. PMID- 2095101 TI - Primary epidermoid carcinoma of the gallbladder. AB - A case of primary epidermoid carcinoma of the gallbladder is presented. It is a very rare pathologic process. The likely etiologic association of infestation by Clonorchis Sinensis with the biliary ducts carcinoma is emphasized. We must remark that in our country exist reports of this parasite in the North-East zone, the same place from where the patient came. The clinical picture, as well as in all incipient carcinomas, reassembled a picture of acute cholecystitis; it's pathologic behaviour, because of obvious reasons, is yet impossible to determine. We suppose that surgery was curative, because until eighteen months later the patient was in a good general condition; unfortunately the patient died from a different cause (acute hematemesis due to rupture of esophageal varices). PMID- 2095102 TI - [Esophageal motility disorders: perspectives at the end of a quarter of a century]. PMID- 2095103 TI - [Lymphoma of the Waldeyer's ring: experience at the National Institute for Cancer Research of Genoa]. AB - Malignant lymphomas account for 3% of all malignant disease in the head and neck area. Twenty-five to fifty percent of all lymphomas arising in this region develop in extra-nodal structures, mostly in the Waldeyer ring. Lymphomas of the Waldeyer ring are comparable to any other lymphomas and prognosis is strictly related to stage and histology. The present paper reports 51 patients with malignant lymphomas arising in the head and neck (25 patients with Waldeyer ring involvement) recorded at the National Institute for Cancer Research, Genoa, Italy, from 1985 to the present. The characteristics of patients with Waldeyer ring involvement are comparable to those reported in the literature. Differences can be found in the median age (older in the present series) and in the incidence of Hodgkin's disease (8%). Patients were treated according to stage: stage I and II received radiation therapy and, in a few selected patients, this was combined with chemotherapy; stage III-IV received chemotherapy followed, in a few selected patients, by radiation therapy. In the present series, survival was related to the involvement of the Waldeyer ring: analysis has shown that survival is better in those patients with only nodal involvement. Nevertheless, these patients usually have a more advanced stage (p = less than 0.03). This finding is quite surprising since all the known prognostic factors are better in the Waldeyer group. PMID- 2095104 TI - [Carcinoma of the lip: a retrospective study of 86 cases]. AB - Carcinoma of the lip is a common lesion which is not always acknowledged as as a potentially lethal disease. The risk of cancer occurs most commonly among aging white men. The risk factors normally associated with lip cancer are rural residence and outdoor occupation. In addition, both actinic radiation and tobacco smoking have been considered casually related to lip cancer. The present study is based on a retrospective review of 86 patients (82 males, 4 females, mean age 65) affected by carcinoma of the lip, treated in Florence from 1970 to 1988. The most frequent site for carcinoma of the lip proved to be the lower lip (71 cases); other sites included the upper lip (7) and the commissure (8). The lip tumor was a squamous cell carcinoma in 82 patients and a basal cell carcinoma in the remaining four. Good prognosis was found for all those with relatively small lesions (T1-T2). On the contrary, the prognosis proved quite poor for those who exhibited tumor fixation to the mandible or erosion of the mandible (23.5%, 5 year survival). Primary radiotherapy may be used for the smaller lesions as cure rates proved equivalent to those achieved surgically although the authors found surgery is always preferable as a primary method of treatment. Surgical excision of the tumor is a relatively minor procedure with a minimum of morbidity as compared with radiation therapy which may lead to local tissue reaction and may disturb function. Surgical management is also recommended as it bears the advantage of being to give a histologically accurate tumor margin assessment. Moreover, with surgery, functional results are good.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095105 TI - [Arteriovenous anastomosis in nasal cavities using microcorrosion technique]. AB - In the present study the morphology of arteriovenous anastomoses in the nasal area are analyzed using the microcorrosion technique. This technique calls for perfusion of the vascular system, passing through the left ventricle, with Batson's of the vessels. For the first time in the microcorrosion study of the nasal vascular network human fetuses (from the 12th to 24th week of intrauterine life) obtained from spontaneous abortions were used as well as rats weighing from 250 to 300 gr. The animals were anesthetized with sodium thiopental prior to administration of the resin. A specimen containing the facial muscles, the nasal pyramid, the maxillary bone and the palatine bones was excised. Then, from this specimen the nasal septum and the two lateral portions of the nose were obtained. The bony and soft perivascular tissues were removed by placing the casts in an aqueous 20% KOH solution. Finally the corrosion cases were observed under a scanning electron microscope (EM). Within the nasal cavities the microcorrosion technique makes it possible to identify three different vascular layers: superficial, intermediate and deep. In the latter it proved possible to visualize the two types of arteriovenous anastomoses: i.e. simple and complex. On the basis of both vascular course and the impressions left by the endothelial cell nuclei it proved possible to differentiate between the arterial and venous portions of the anastomoses. PMID- 2095106 TI - [Mechanical sutures of the pharynx during total laryngectomy: proposal of a closed technique]. AB - The authors present the results of a pharyngeal autosuture technique using a 55 mm linear stapler during total laryngectomy. The stapler is inserted before the larynx has been removed, but after it has been separated from its muscular and neuro-vascular connections and after it has been adequately elevated so that no part remains within the instrument jaws. This "closed" procedure is quite rapid, does not soil the operating field and is safe in the long run. The patient does not require a feeding tube since he can swallow from the third day after surgery. None of the patients treated with this technique produced either early or late fistulas, nor did they encounter any trouble in swallowing. PMID- 2095108 TI - [Use of irradiated bovine cartilage in the correction of defects of the nasal structure]. AB - Reference is made a personal experience in the use of treated and irradiated bovine cartilage (Chondroplast) in the correction of bone and cartilage defects of the nasal structures. On 14 patients 25 Chondroplast grafts, single or multiple grafts, were performed with an average follow-up of 15.5 months (4-27 months). The Chondroplast prove quite moldable, easy to use, did not cause allergies or rejection. In one of the patients (7.1%) a post-operative infection arose which was readily treated by broad-spectrum antibiotics without requiring removal of the graft. In one other case (7.1%), after three months, it was observed that the graft had shifted. The author attributes both these complications to technical errors (Was the pocket housing the graft too big? Was there intra-operative contamination?) rather than to characteristics of the material. On the other hand, a different behaviour was found inherent to reabsorption which was evaluated three months after surgery and then again for all cases, in September, 1989 (average 15.5 months after surgery). Upon careful clinical examination a grade ranging from + to + + + + was given according to entity (minimal, significant, marked, total). Three months after surgery no reabsorption was found while this not the case upon examination in September 1989 (average 15.5 months). At this time, of the 25 grafts, 5 (20%) had total reabsorption, 3 (12%) had marked and 3 (12%) minimal reabsorption while 14 (56%) showed no evidence of reabsorption at all. The greatest degree of reabsorption was observed in those sites where the tension was greatest (columella, anterior nasal column). More precisely, out of a total of 9 reconstructions between the column and the columella 4 (44.4%) presented total and 3 (33.3%) marked reabsorption while there were no cases of minimal or significant reabsorption. Moreover, there were only 2 (22.2%) cases which remained unaffected. Reabsorption proved least or non existent where there was the least tension (back, zygoma, septum). In fact, out of a total of 18 reconstructions (12 back, 5 septum and 1 zygoma) only one case (5.5%) of total reabsorption was found, no cases of marked or significant reabsorption and 3 cases (16.6%) of minimal reabsorption. Fourteen cases remained intact (77.7%). It would, therefore, appear that Chondroplast is a suitable graft material if it is not subjected to tension. PMID- 2095107 TI - [Transcranial magnetic stimulation of the facial nerve: evaluation of a new method in neurophysiological study of Bell's palsy]. AB - Transcranial magnetic stimulation is a new technique used to stimulate brain areas as well as peripheral nerves in healthy, waking persons. To date this technique has appeared safe. The aim of the present study was to assess the clinical application of this method in patients with Bell's palsy. Electromyographic responses were elicited by electrical and magnetic transcranial stimulation of the facial nerve in 26 patients affected by Bell's palsy. Electrical stimulation: stimuli of 0.1 ms duration, and up to 15 V, were delivered through surface electrodes set 2.5 cm apart over the facial nerve at the stylomastoid foramen. Magnetic stimulation: the coil was placed tangent to the parieto-occipital surface of the scalp. The stimulus intensity was then increased stepwise until a supramaximal response was obtained. Recording: the focal recording electrode was placed ipsilateral to the side stimulated over the superior orbicularis oculi; the reference electrode was placed over the nasal bone. The patients were tested with two neurophysiological determinations: the first 15-30 days from the onset of the palsy; the second 30-60 days after the first. A clinical follow-up was performed six months after the second determination. The results indicate that, contrary to traditional electroneurography, transcranial magnetic stimulation is not able to supply useful neurophysiological indications in patients with Bell's palsy. Although the absence of compound muscle action potential upon stimulation of the side with the lesion did demonstrate some impediment to conduction, it did not have any prognostic value since it was also present in patients who were clinically well at the time of the second check-up. PMID- 2095109 TI - [Modified Semont's maneuver in the treatment of benign paroxysmal positional vertigo]. AB - Benign paroxysmal positional vertigo (BPPV) is one of the most frequent causes of vertigo. It is characterized by a peripheral balance impairment which occurs during specific movements or positions of the head. The etiology of BPPV is not clear although recent studies by Harada have given more weight to the otolithic theory. The present author has found frequent otoconia attached to the dark cell area around the crista of the semicircular canals. The treatment of BPPV is based on functional re-education of the patient (Semont maneuvers, the Brandt Daroff technique, Norre's V.H.T). The present study involves 62 patients affected by BPPV. The Hallpike maneuver was employed to define the affected side and then the modified Semont maneuver was performed. Recovery was obtained in all patients. The cure rate proved to be 82% after the first examination. The modified Semont maneuver is easier to perform than the traditional maneuver and has given excellent therapeutic results. PMID- 2095110 TI - [Acute respiratory obstruction caused by laryngo-tracheal candidiasis in a HIV positive patient]. AB - The authors report a case presenting highly complex symptomatology. In fact, when the patient came under observation he had had a cough, dyspnea, dysphagia and dysphonia for approximately three months. The biopsy, taken by direct laryngoscopy, indicated the presence of candidiasis in the subglottic and tracheal areas. Laboratory tests indicated complete anergy and patient tested serum positive to HIV. During hospitalization acute dyspnea arose requiring emergency tracheostomy. PMID- 2095112 TI - [Importance of the clinical aspects of congenital cardiopathies facing the technological advances]. PMID- 2095111 TI - [Surgical rehabilitation of glottic and neoglottic insufficiency using Gax Collagen (Phonagel)]. PMID- 2095113 TI - [The coronary flow reserve during reperfusion in myocardial infarction]. AB - PURPOSE: The study of coronary flow reserve on the reperfused myocardium damaged by 90 minutes of severe ischemia. MATERIAL AND METHODS: Nine mongrel dogs of either sex, weighing 12 to 17 kg were studied. Each dog was anesthesiated with 30 mg of pentobarbital and ventilated with room air. A thoracotomy was done and the left descendent coronary artery was isolated. Aorta and right atria pressures was measured using a Siemmens-Elema transducers and mingograf recording-804 (Siemmens Instruments). Coronary blood flow was measures with a Caroline Medical Electromagnetic flowmeter, 501D. The index studied was the coronary resistance, calculated as the quotient of the diastolic aortic pressure and the diastolic blood flow. The coronary reserve was studied during reactive hyperemia produced by 10 seconds of coronary occlusion in the 5, 10, 15 and 20 minutes of reperfusion. The infarcted area was detected by TTC (triphenyltetrazolium) method. RESULTS: All the hearts examined showed infarcted area. The diastolic coronary resistance during the reactive hyperemia in the 20 minutes of reperfusion was higher than the control value. CONCLUSION: The coronary vascular reserve was decreased during reperfusion, in the myocardial infarction. PMID- 2095114 TI - [Results of replacement of ascending aorta, and aortic valve with reimplantation of coronary arteries]. AB - PURPOSE: To analyse a 10-year experience with the Bentall and De Bono technique for surgical treatment of aneurysms of ascending aorta. PATIENTS AND METHODS: From January 1980 to December 1989, the Bentall and De Bono technique was employed in 38 patients. Twenty-two patients had aneurysm of ascending aorta with aortic insufficiency; 14 had chronic aortic dissections. Four patients were operated on previously by other techniques. RESULTS: The immediate mortality was 5.2%; one patient due to low-output syndrome and one had neurological complications. Five patients (13.1%) died late postoperatively. The surviving 31 patients were followed up from two to 72 months (mean 25). Of these, 29 (93.5%) were in functional class I and two in class II. Sixteen patients had late evaluation by one or more of the following methods: digital angiography, chest computerized tomography, echocardiography, or conventional angiography, 6 to 60 (mean 33) months after operation. All of them had good conditions of composite valve graft and coronary artery reattachment. The immediate and late results were similar in patients with aneurysms and aortic dissections. CONCLUSION: The aortic valve and aortic ascending portion replacement with reimplantation of coronary arteries is of low mortality and fairly good late outcome. PMID- 2095115 TI - [Evaluation of cardiac manifestations in hypothyroidism: documentation of reversibility]. AB - PURPOSE: To detect the cardiac manifestations due to the state of hypothyroidism and reversibility after euthyroidism. PATIENTS AND METHODS: Thirteen patients with documented primary hypothyroidism were evaluated through the echocardiography and other noninvasive techniques. A new evaluation was performed six months after thyroid hormone therapy. RESULTS: Most of the changes were reversed after the patients became euthyroid. The main finding was the echocardiographic measurement of the velocity of circumferential fiber shortening that showed a significant positive linear correlation with serum thyroid hormones. CONCLUSION: These data demonstrate the existence of a hypothyroid cardiomyopathy. PMID- 2095116 TI - [Nutritional index in heart diseases in childhood]. AB - PURPOSE: To study heart disease in childhood aiming to know its incidence and consequences upon the nutritional status. PATIENTS AND METHODS: Two-hundred patients were distributed in three groups: 1) 113 (56.5%) with congenital acyanotic form; 2) 19 (9.5%) with congenital cyanotic form and 3) 68 (34%) with acquired forms. All of them regularly visiting the ambulatory service of Paediatric cardiology of the Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da USP from 1987 until 1990. RESULTS: The majority (92%) of the children (being 56% male and aging 5.1 +/- 0.4 years-old) showed nutritional indexes between 5 and 95 (percentile scale). The overall diagnosis distribution were: 1) ventricular septal defect (51 cases); 2) atrial septal defect (21 cases); 3) valvular diseases (21 cases); 4) arrhythmias (20 cases); 5) cardiac involvement of systemic diseases (20 cases); and 6) tetralogy complex (8 cases). Twelve patients (6%) were underscored (below percentile 5) and only 4 (2%) scored above percentile 95 (obese patients). The comparison of the mean indexes were found statistical different (p less than 0.05), being the cyanotic congenital forms the worst ones and the acquired forms the best one. CONCLUSION: Heart disease in childhood is associated to nutritional index deficits in the majority of the cases. PMID- 2095117 TI - [Death in exercise test: immediate angiographic findings in 2 cases]. AB - We present two cases of mortality during a stress test after which coronary arteriography was performed after the acute event. In both patients, left coronary arteries presented eccentric lesions with irregular bordes and intraluminal lucencies. We have discussed the probable pathophysiologic mechanisms involved in view of the angiographic findings. We concluded that the cracking of the plaque was an essential event in the pathogenesis of this picture. PMID- 2095118 TI - Spontaneous closure of ventricular septum rupture after acute myocardial infarction. PMID- 2095119 TI - [Tuberous sclerosis associated with left ventricle rhabdomyoma]. AB - Female infant, presenting with flexion spasms, skin hypochromatic spots and systolic ejection murmur. A clinical diagnosis of tuberous sclerosis, supported by computerized brain tomography and neurosonographic data, was made. Echocardiographic and cineangiocardiographic studies disclosed an associated tumor in left ventricle outlet. After resection of the rhabdomyoma, the patient is asymptomatic with neural manifestations controlled under valproic acid. PMID- 2095120 TI - [Staphylococcus aureus endocarditis in a puerperal woman with mitral and tricuspid valve prolapse]. AB - A 17-year-old woman with mitral and tricuspid valve prolapse and myxomatous degeneration presented puerperal infection by Staphylococcus aureus with clinical picture of sepsis and multiple septic embolism (right eye, left thumb, spleen, and left calf). She underwent total hysterectomy on the 10th day postdelivery and right eye enucleation on the 16th. Temporary total AV block occurred on the 14th day with temporary external pacing during the next couple of days. Acute endocarditis with acute mitral regurgitation was diagnosed on the 13th day, demanding immediate valve replacement. On the 46th day she developed moderate tricuspid valve regurgitation due to another episode of endocarditis. Final clinical discharge took place on the 62nd day after antibiotic therapy completion. PMID- 2095121 TI - [Cardiovascular function in patients with sepsis]. PMID- 2095122 TI - [Bentall/De Bono surgery. The best option?]. PMID- 2095123 TI - [Nutritional index in congenital cardiopathies in childhood]. PMID- 2095124 TI - A new homologous series of anticonvulsants: phenyl alcohol amides. Synthesis and pharmacological evaluation. AB - The anticonvulsant activity of a homologous series of phenyl alcohol amides is described. (+-)-2-Hydroxy-2-phenylbutyramide (1), (+-)-3-hydroxy-3 phenylpentanamide (2) and (+-)-4-hydroxy-4-phenylhexanamide (3) were prepared and tested for their anticonvulsant profile and neurotoxicity. 1, 2 and 3 exhibited a broad profile of anticonvulsant activity and a similar significant activity in the seizures provoked by maximal electroshock, pentetrazol, 4-aminopyridine, bicuculline and thiosemicarbazide, but in the strychnine and picrotoxin tests, the protection was variable. The rotarod ataxia test was used to evaluate their neurotoxicity. In this test 2 possesses the lowest neurotoxicity. PMID- 2095125 TI - Protective effect of the novel anti-ischemic agent 2-(4-(p-fluorobenzoyl) piperidin-1-yl)-2'-acetonaphthone hydrochloride against ischemia-induced impairment of the passive avoidance response in gerbils. AB - E2001 (2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride, CAS 107025-80-9) is a novel anti-ischemic agent, which is reported to protect against delayed neuronal death in the CA1 subfield of the hippocampus. The effect of E2001 on ischemia-induced impairment of the passive avoidance response in gerbils was studied. The passive avoidance response was not disturbed by transient cerebral ischemia of 3 min duration, but was impaired by 5-min ischemia. E2001 at oral doses of 3 and 10 mg/kg significantly improved the impaired passive avoidance response induced by 5-min cerebral ischemia. It is speculated that the improvement by E2001 may be partly due to the inhibition of extracellular glutamate accumulation, and the suppression of lipid peroxides formation during cerebral ischemia. PMID- 2095127 TI - Catecholamine metabolism in heart failure patients and healthy control subjects. AB - Parameter of catecholamine metabolism were examined in patients (Groups II to V) in chronic, stable stages of coronary heart disease (n = 45), dilated cardiomyopathy (n = 17) and healthy control subjects (Group I). Plasma and urinary catecholamine patterns, catecholamine plasma half-life and catecholamine metabolism following administration of levodopa were determined. In cases of slight (Group II, ejection fraction (EF) 54 +/- 7%) to marked left-heart damage (Group III, EF 44 +/- 5%), the findings indicate elevated catecholamine excretion and a beginning reduction of plasma clearance as the cause of excessive, circulating and renally excreted catecholamines (applies to noradrenaline, less to adrenaline). The renal 24-h dopamine elimination is already slightly reduced in these patients. In cases of severe left-heart damage, the findings are not uniform. In some cases, noradrenaline at rest and at comparable exercise levels are elevated (Group IV, EF 20 +/- 11%), in some cases they are normal (Group V, EF 16 +/- 4%). The 24-h dopamine elimination is reduced in both groups to 34-41% of normal. Noradrenaline and adrenaline elimination is normal, or reduced (Group V, adrenaline). The exercise-induced, maximum plasma noradrenaline concentrations in Group IV and V are much lower (33-40% of normal) than in the healthy control individuals and patients in Groups II and III. Oral administration of 2-4 g levodopa per day result in a 20- to 40-fold dopamine increase in patients with heart failure (Group IV) and healthy control persons (Group I) (free and conjugated plasma dopamine, as well as free urinary dopamine).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095126 TI - Hypotensive and hemodynamic effects of the new non-sulfhydryl angiotensin converting enzyme inhibitor N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline. AB - The hypotensive effects of N-[8-amino-1(S)-carboxyoctyl] -L-alanyl-L-proline (AB 47, CAS 120008-53-9) were examined in normotensive rats and various hypertensive rat models. The hemodynamic effect of AB-47 was also examined in anesthetized spontaneously hypertensive rats (SHR). In 2-kidney, 1-clip renal hypertensive rats (2K, 1C-RHR) and SHR, the single administration of AB-47 (10 mg/kg, p.o.) induced potent and long-lasting hypotensive effects. The repeated administration of AB-47 (1 to 10 mg/kg, p.o.) to SHR for 29 days produced a dose-dependently and sustained hypotensive effect of 20 to 70 mmHg. AB-47 (10 mg/kg, p.o.) had a weak hypotensive effect in DOCA-salt hypertensive rats but no effects in normotensive and 1-kidney, 1-clip renal hypertensive rats (1K, 1C-RHR). AB-47 (3 mg/kg, p.o.) reduced blood pressure in intact SHR but not in bilateral nephrectomized SHR. The single intravenous injection of AB-47 (10 to 100 micrograms/kg) dose-dependently lowered systemic blood pressure, left ventricular systolic pressure (LVSP) and dp/dtmax without affecting heart rate (HR) and these effects of AB-47 were more potent than those of captopril and enalaprilat. These results suggest that AB-47 is a potent and long-lasting hypotensive agent and may be useful for the therapy of both hypertension and congestive heart failure. PMID- 2095129 TI - Chelators affecting iron absorption in mice. AB - The effect of natural and synthetic chelators on iron (59Fe) absorption in mice has been studied in three different experiments using single or repeated intragastric administrations of chelator iron (59Fe) complexes of different chelator doses. The amount of 59Fe in whole animals, their excretions and also distribution of 59Fe in blood, liver, spleen and heart was measured at one, three and eight weeks following the 59Fe-chelator administrations and compared to controls which received the same amount of iron (59Fe) but no chelator. 2-Hydroxy 4-methoxypyridine-1-oxide and maltol, which form lipophilic iron complexes, were found to cause an increase of 59Fe absorption while other chelators caused a decrease either by precipitating iron eg. 2-hydroxypyridine-1-oxide or by forming non absorbable soluble iron complexes eg. desferrioxamine, mimosine, EDTA. 1,2 Dimethyl-3-hydroxypyrid-4-one caused a decrease in iron absorption at a high dose (10 mg) by comparison to the control group but it did not significantly alter iron absorption at a lower dose (2 mg). It is suggested that natural and synthetic iron chelating compounds influence the absorption of iron and some may have a use in the treatment of diseases associated with gastro-intestinal iron absorption imbalance. PMID- 2095128 TI - Cyclic guanidines: synthesis and antiplatelet activity of 4,6,7,8-tetrahydro-1H imidazo[1,2-a]pyrazolo[3,4-d]pyrimidin-7-ones and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido[2,1-c] [1,2,4]triazin-7-ones. AB - A series of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo [3,4-d]pyrimidin-7-ones (1b-n) and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido [2,1 c][1,2,4]triazin-7-ones (2a-d) has been synthesized. In view of their potential anti-aggregating activity the compounds were tested in vitro for inhibitory activity towards ADP- and collagen-induced aggregation of human platelets. Among the compounds studied, 8-benzyl-1-(2,5-dichlorophenyl)-4,6,7,8-tetrahydro-1H imidazo [1,2-a]pyrazolo[3,4-d]pyrimidin-7-one (1n) exhibited the most favorable activity. The 2,5-dichlorophenyl side chain is an important lipophilic and/or steric pharmacophore. PMID- 2095130 TI - Pharmacokinetics of dimetindene after intravenous and oral administration to healthy volunteers. AB - The pharmacokinetics of dimetindene (dimethindene maleate, Fenistil, CAS 3614-69 5) were studied after its intravenous and oral administration to 8 healthy male volunteers. Serum concentrations were measured for 48 h using an enzyme-linked immunosorbent assay. Pharmacokinetic parameters (AUC, t1/2, CLs, Vd and F) were calculated using the clearance approach. PMID- 2095131 TI - New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidine derivatives as diuretics. AB - New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidines 1 and 6,10-dihydro-5H pyrido[3',2':5,6]pyrimido[2,1-c] [1,2,4]triazines 4 with 5-one, 5-thione or 5 hydrazono substituents and in some cases 1,2,3,4 or 8,9 hydrogenated are synthetized. The diuretic, natriuretic and kaliuretic activities of these compounds in Wistar rats at a dose of 24 mg/kg were estimated. A series of 24 possible derivatives of 1 and 4 possessing diuretic and saliuretic activities are investigated for structure-activity relationships in light of Fujita-Ban model. The Fujita-Ban group contributions have been calculated for different structural variations on the parent ring 1a. It is observed that the hydrogenation of pyridine, [1,3]thiazole or [1,2,4]triazine rings on 1 or 4 decrease the diuretic and saliuretic activities. PMID- 2095132 TI - Pharmacological studies of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2 yl)amino]benzoate dimethanesulfonate. Effects on experimental pancreatitis. AB - The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2 yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10 100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis. PMID- 2095133 TI - [Pharmacokinetics and bioequivalence of two ibuprofen formulations]. AB - In an open controlled randomized cross-over study in 16 healthy male and female volunteers the bioavailability of ibuprofen (CAS 15687-27-1) sugar-coated tablets (Dolo-Dolgit) was tested versus film-coated tablets containing ibuprofen 600 mg. As it results from the AUC evaluation, the bioavailability of both preparations is very good and almost identical. The ibuprofen concentrations achieved after administration of the test preparation, however, are significantly higher (Cmax = 52.03 micrograms/ml) than those achieved after the reference preparation showing a Cmax of 40.32 micrograms/ml. The tmax of 1.0 h is also significantly shorter than after the reference preparation (tmax = 1.5 h). The t1/2 beta after both the test and the reference preparation is within the known range, i.e. 1.8 h and 1.4 h, respectively. Even in long-term treatment with high dosages, administered 3-4 times daily, there is no accumulation of the active ingredient. Concerning the therapeutic relevance, special attention is to be given to the different time dependent drug concentrations in the central compartment and in the target compartment. Both the higher Cmax and the shorter tmax achieved following administration of the test preparation are of therapeutic relevance. PMID- 2095134 TI - Liposomes from soya phospholipids as percutaneous drug carriers. 1st communication: qualitative in vivo investigations with antibody-loaded liposomes. AB - The penetration behaviour of liposome (prepared from NAT 106)-incorporated proteins was investigated in vivo by use of monoclonal antibodies (MOAB) as model substances on the skin of young pigs. Within 20 min of topical application, an even distribution of liposome-incorporated antibodies through all skin layers could be shown by means of an immunohistochemical stain. PMID- 2095135 TI - Significance of empty liposomes alone and as drug carriers in dermatotherapy. AB - The influence of three different liposome formulations (NAT 106, NAT 50, NAT 89), as empty liposomes and loaded with 0.05% betamethasone, on blood circulation in the corium was investigated by means of laser Doppler flowmetry. All three empty liposomes brought about a decrease in circulation. The maximum effect was reached 90 min after a 30-min occlusive application of the test preparations. Loading with betamethasone resulted in a significant increase in circulation after only 15 min. This increase in interpreted as a steroid effect. No comparable symptoms appeared with the application of base cream DAC (an O/W emulsion) or of betamethasone in base cream under identical experimental conditions. PMID- 2095136 TI - Inhibition of hepatitis B virus polymerase-activity by various agents. Transient expression of hepatitis B virus DNA in hepatoma cells as novel system for evaluation of antiviral drugs. AB - The effect of three putative antiviral drugs--aciclovir (acyclovir, CAS 59277-89 3), zidovudine (azidothymidine, CAS 30516-87-1) and sorangicin B (a macrocyclic lactone, CAS 100415-25-6)--on replication and gene expression of hepatitis B virus (HBV) was studied in HepG2 cells. Transfection of these cells with cloned circular HBV DNA resulted in the production and secretion of virions into the medium. When antiviral drugs were added in increasing concentrations (aciclovir at 0.5 microgram/ml to 150 micrograms/ml, zidovudine 0.1 microgram/ml to 30 micrograms/ml, sorangicin B 1 micrograms/ml to 30 micrograms/ml), the activity of the viral polymerase decreased in a dose-dependent manner. Production of viral proteins as measured by the secretion of HBsAg and HBeAg into the medium was unaffected, suggesting interference of these drugs with viral DNA/RNA synthesis. It is concluded that aciclovir, zidovudine and sorangicin B inhibit the replication of HBV. Furthermore, the cell system used in our study appears to be suitable for the rapid testing of antiviral drugs and their evaluation for possible studies in vivo. PMID- 2095138 TI - John Humphreys. PMID- 2095137 TI - Amplification of bacterial 16S ribosomal DNA with polymerase chain reaction. AB - The sequence of small-subunit rRNA varies in an orderly manner across phylogenetic lines and contains segments that are conserved at the species, genus, or kingdom level. By directing oligonucleotide primers at sequences conserved throughout the eubacterial kingdom, we amplified bacterial 16S ribosomal DNA sequences with the polymerase chain reaction. Priming sites were located at the extreme 5' end, the extreme 3' end, and the center of 16S ribosomal DNA. The isolates tested with these primers included members of the genera Staphylococcus, Coxiella, Rickettsia, Clostridium, Neisseria, Mycobacterium, Bilophila, Eubacterium, Fusobacterium, and Lactobacillus and the family Enterobacteriaceae. Initially, the yields from the reactions were erratic because the primers were self-complementary at the 3' ends. Revised primers that were not self-complementary gave more reproducible results. With the latter primers, 0.4 pg of Escherichia coli DNA consistently gave a visible band after amplification. This method should be useful for increasing the amounts of bacterial 16S ribosomal DNA sequences for the purposes of sequencing and probing. It should have a broad range of applications, including the detection and identification of known pathogens that are difficult to culture. This approach may make it possible to identify new, nonculturable bacterial pathogens. PMID- 2095139 TI - [Enuresis and urinary pathology]. AB - The incidence of urinary pathology is studied in 71 pediatric cases of primary nocturnal enuresis. These incidences have been 18.3 per cent, but there are two different groups. After a negative urological anamnesis, incidence goes down to 5.4 for 100 (3 patients of 55). When anamnesis shows suspicious of uropathy, incidence growth to 62.5 for 100 (10 patients of 16). Urological study with ultra sound and XR is recommended in nocturnal enuretic children only when there are suspicions of uropathy after a detailed clinical exploration and anamnesis. PMID- 2095140 TI - [Primary surgical pathology of the epiploon]. AB - In the last nine years we have operated upon six children (eight males and two females) with primary omental pathology. The age of our patients ranged from five to eleven years with the exception of a newborn prenatally diagnosed of lymphangioma. All the remaining children had abdominal pain and right iliac tenderness for an average of two days. All had leukocytosis and left shift. Vomiting and fever were present only in one instance. In no case the mass was palpated preoperatively. The initial diagnosis was acute appendicitis in all cases. A patient suffered, one year after operation, a second acute clinical picture and the omental mass could be revealed [correction of decealed] preoperatively. At operation there was free intraperitoneal fluid in six instances (three times bloody, two times clear and one purulent). Surgical findings (nine operations) were: three omental segmental infarctions (primary in two cases and secondary to torsion in one), three segmental epiploitis in two patients (one acute, one chronic, one secondary to foreign body), two cystic lesions (one lymphangioma, one hydatic cyst) and one benign tumor (fibromatosis). PMID- 2095141 TI - A comparative study of the shear stress induced in the leakage backflow produced by four types of heart valve prostheses. AB - The clinical selection of a prosthetic heart valve requires the consideration of many factors. These include the pressure drop across the prosthesis, the amount of leakage backflow when the valve is closed as well as the associated shear stress within this flow for a particular valve design. Major emphasis has been placed upon the documentation of the pressure drop across prosthetic valves. Consideration of the shear stress induced in the leakage backflow associated with prosthetic valves, however, has received less attention. The purpose of this investigation, therefore, is to determine theoretically the extent of this particular shear stress for four types of currently used mechanical prosthetic cardiac valves. All valves have the same tissue annulus diameter of 27 mm. The leakage backflow is relatively small compared to the main forward flow through the orifice. However, it is important from the haemolysis point of view. The effect of the shear stress on the suspected occurrence of haemolysis is analysed by two theoretical approaches: (a) the laminar flow approach, and (b) the entry flow approach, and then compared with the findings of previous investigators dealing with the critical shear stresses which may damage the red blood cells. It was found that both approaches give practically equal shear stresses under the same pressure differential for all valves investigated. Some haemolysis is expected to occur but it is generally compensated by bone marrow hyperfunction, since that type of shear stress is sustained for only a short duration of time. PMID- 2095142 TI - The effect of variation in structure on the Young's modulus of cancellous bone: a comparison of human and non-human material. AB - The Young's modulus of cubes of human cancellous bone was measured in three orthogonal directions. Apparent density and mineral volume fraction were also measured, as were two architectural variables, fabric and connectivity, which were determined using image analysis techniques. Multiple regression was used to relate the Young's modulus to the four explanatory variables. The results from this study are compared with those obtained from a previous investigation using non-human cancellous bone. The relationships revealed by the two studies are very similar. It was possible to explain approximately 93 per cent of the variance in Young's modulus using the four variables in this present study. Apparent density is the major explanatory variable in both studies and shows a strong correlation with connectivity. In common with the non-human study the measure of fabric is a worthwhile explanatory variable; however, connectivity and mineral volume fraction are relatively unimportant. The four explanatory variables contribute to a successful model for the prediction of Young's modulus. Any other candidate variables are likely to be unimportant or be highly correlated with those already investigated. PMID- 2095143 TI - Acoustic emission from trabecular bone during mechanical testing: the effect of osteoporosis and osteoarthritis. AB - This study examines the relation between the nature of acoustic emission signals emitted from cancellous bone under compression and the mechanical properties of the tissue. The examined bone specimens were taken from 12 normal, 31 osteoporotic and six osteoarthritic femoral heads. The mechanical behaviour of the osteoporotic bone specimens was found to be significantly different from that of the normal specimens both in the pre-yield and post-yield ranges. In the osteoarthritic bones only the elastic behaviour was significantly different. The rates of acoustic events before yield and beyond it were found to be significantly higher both in the osteoporotic and osteoarthritic bone specimens. The average peak amplitude of the signals was also significantly higher in the diseased bones. Stepwise regression analysis showed that a combination of the acoustic emission parameters could significantly predict some mechanical properties of the bone. The energy absorbed during compression and the ultimate compressive stress of the specimens could be estimated from the rate of pre-yield acoustic events, the average amplitude of the signals and the rate of post-yield events. However, the explanation power of the acoustic emission parameters was only moderate. The nature of acoustic emission signals was thus demonstrated to be a potential tool for assessing bone quality. PMID- 2095144 TI - A simple instrument for the measurement of maximum occlusal force in human dentition. AB - A simple instrument for the measurement of maximum occlusal force has been developed and the results of an initial clinical trial have been reported. The maximum occlusal force in subjects with dentures was significantly lower than in a group of young male subjects with natural dentition. In the young males the bite force between the molars and premolars was significantly greater than between the incisors. The maximum bite force was not dependent on position for subjects with dentures. PMID- 2095145 TI - Socket size and the expected quality of its fixation in the cemented total hip arthroplasty. PMID- 2095146 TI - Transient vibrations caused by heel strike. PMID- 2095147 TI - Objective measurement of knee laxity and stiffness with reference to knee injury diagnosis. Part 1: Design considerations and apparatus. AB - Apparatus capable of objectively evaluating the laxity of the knee in vivo has been developed. The equipment consisted of a microcomputer-controlled machine, into which the leg was firmly clamped. The mechanical properties of the knee were measured by slowly applying a load to the tibia, while the femur was held stationary, and monitoring the resulting displacement of the tibia. Three separate tests could be performed: anterior-posterior drawing, varus-valgus rotation and tibial rotation. The tests were carried out on both legs of each subject, making six tests in all. The forces versus displacement (or torque versus rotation) took the form of a hysteresis loop. From these a total of 24 variables describing the stiffness, laxity and visco-elastic properties of the knee were calculated. PMID- 2095148 TI - Objective measurement of knee laxity and stiffness with reference to knee injury diagnosis. Part 2: Results. AB - Equipment capable of objective knee analysis has been used to obtain data from 85 'normal' healthy knees, 47 patients suffering with knee disorders, and three cadaveric knee joints. Among the 'normals' it was found that there was a correlation between body weight and stiffness and laxity. A lower stiffness and higher laxity was recorded at 20 degrees of knee flexion than at 90 degrees. Using relative-paired difference analysis the variables affected by different injuries in patients were identified and are presented. In a separate analysis a multi-variate technique is used to interpret the data. The technique could be used to predict or diagnose knee injury, and as such may be highly useful to clinicians. PMID- 2095149 TI - Analysis, design and development of a carbon fibre reinforced plastic knee-ankle foot orthosis prototype for myopathic patients. AB - A traditional knee-ankle-foot orthosis (KAFO) for myopathic patients has been studied for the assessment of loads and fatigue resistance. Starting from this basis a thermoplastic matrix carbon fibre reinforced plastic composite (CFRP) KAFO has been developed in order to reduce the weight. A finite-element simulation programme for deformation analysis was used to compare the behaviour of conventional and CFRP orthosis. There were no breakages either of the prototype or of its parts. The CFRP orthosis allows a weight reduction of more than 40 per cent. PMID- 2095151 TI - Aspects of the medicinal chemistry of fluoroorganic compounds. Part I. PMID- 2095150 TI - Femoral strain adaptation after total hip replacement: a comparison of cemented and porous ingrowth components in canines. AB - The purpose of this study was to investigate if experimental strain analysis is predictive of femoral adaptation after total hip replacement (THR). Ten large adult dogs underwent unilateral THR with identical implants. Five implants were press fit for porous ingrowth fixation, and five were cemented. Four months after surgery femora were harvested. Strain gauge rosettes were applied to the femora at eight proximal locations. Femora were compressively loaded on the head of the femur or femoral component. Strain data represented three conditions: preoperative, acutely postoperative, and four-month postoperative. The unoperated femur of each dog was used to simulate preoperative and acutely postoperative behavior of the contralateral implanted femur. Strains from each condition were compared. Transverse femoral sections were obtained through the levels of the strain gauges. Fine detailed radiographs were used to quantify morphological changes. Results showed cemented and uncemented implantations produce similar trends but different amounts of bone adaptation. Adaptations were generally consistent in direction with strain perturbations caused by implantation, but the extent of adaptation did not strongly correlate with the magnitude of perturbations. Also, there was no consistent trend towards normalization of altered strains. Results suggest that strain perturbations after THR may be mechanical triggers for morphological changes, but caution is required when predicting the extent of these changes or the autoregulatory role of strain. PMID- 2095152 TI - The effect of membrane lipid molecular species on rat brain base-exchange reactions: an appraisal of phosphatidylserine and of polyunsaturated phosphatidylcholine. AB - Rat brain microsomal membranes were solubilized with octyl glucoside and reassembled by removing the detergent. The composition of reconstituted membranes was modified by adding exogenous lipid to the detergent-membrane mixtures. The base-exchange reactions were sensitive to these procedures. The inhibiting or activating capacity of added lipid was related to the charge of polar head groups; indeed, the addition of phosphatidylserine always resulted in inhibition and that of phosphatidylcholine very often in activation. The addition of phospholipid possessing unsaturated acyl chains inhibited less (or activated more) serine and choline base-exchange than the addition of saturated species. It is concluded that phosphatidylserine and polyunsaturated phosphatidylcholine have opposite effects on base-exchange. PMID- 2095153 TI - Research on heterocyclic compounds. XXVII. Synthesis and antiinflammatory activity of 2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acids. AB - A group of ethyl esters of 2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acids 3 were obtained by reaction in anhydrous ethanol of some substituted 3 aminopyridazines 1 with ethyl 2-benzoyl-2-bromoacetate 2. The acids 4 obtained via alkaline hydrolysis were tested in vivo for their antiinflammatory, analgesic and ulcerogenic actions and in vitro for their ability to inhibit the prostaglandin biosynthesis. Almost all of the new compounds showed high analgesic activity, whereas the activities exhibited in the other tests were sharply lower. These results are discussed in terms of mechanism of action. PMID- 2095154 TI - Gastrointestinal activities of a new pirenzepine-analog, nuvenzepine, in the cat. AB - Nuvenzepine, a new pirenzepine-analog, administered intraduodenally, displayed a long-lasting and dose-dependent inhibition of neostigmine-induced intestinal motility in anaesthetized cats. On ileal motor activity, the compound showed a potency 10 times greater than that of pirenzepine, and, although to a lesser extent, it was also active, unlike pirenzepine, on colonic stimulated motility. Furthermore, in conscious cats, nuvenzepine inhibited pentagastrin-stimulated gastric acid secretion resulting 25-30 times more potent than pirenzepine. The observed differences between antisecretory and antispastic activities displayed by nuvenzepine and pirenzepine suggest that the new pirenzepine-analog may act on gastrointestinal functions through an additional non-anticholinergic mechanism. PMID- 2095155 TI - Antimicrobial activity of some isothiosemicarbazones. AB - The microbiological activity of a series of isothiosemicarbazones is reported. The experimental data relating to the microbiological screening show an interesting antibacterial activity associated to a good antifungal activity. PMID- 2095156 TI - Determination of sulfametrole in commercial dosage forms (Lidaprim) by TLC densitometry. PMID- 2095157 TI - Studies on structures of some platinum complexes with 1,1 cyclopropanedicarboxylate. AB - The crystal structures of [Pt(NH3)2CPrDCA].H2O (I), [Pt(CH3NH2)2CPrDCA] (II), and [Pt(dmbn) CPrDCA].2.5H2O (III) (where CPrDCA is 1,1-cyclopropanedicarboxylate; dmbn is 2,3-dimethyl-2,3-butyldiamine) are determined. Compound I crystallizes in the orthorhombic space group Pnma with the cell dimensions: a = 6.517(2), b = 9.709(3), c = 14.205(5) A, Z = 4, R = 0.058. Compound II is monoclinic with space group P2(1)/n, a = 9.648(3), b = 8.720(2), c = 12.770(4) A, beta = 107.12(2), Z = 4, R = 0.059. Compound III belongs to the monoclinic system space group P2(1)/m with the cell dimensions: a = 6.494(1), b = 19.638(3), c = 6.606(1)A, beta = 94.44(1), Z = 2, R = 0.038. Electronic structures of the complexes are studied and the correlation between structure of the amine ligands and biological activity of the complexes is explored. PMID- 2095158 TI - The double porosity model for mass transfer between capillaries and tissues in lung microcirculation. AB - This paper proposes a double porosity model to deal with the mass transfer between capillaries and tissues in the lung microcirculation on the basis of. Utilizing the analytic method of small parameter expansion and the numerical method, the nonlinear governing equations are solved. Comparison shows that the small parameter solution is accurate enough to illustrate the mass exchange between the lung capillary and tissues. Finally the results are used to discuss the mechanism of formation of lung edema. PMID- 2095160 TI - Treatment of patients with acute myocardial infarction with intravenous magnesium. AB - Acute myocardial infarction (AMI) accounts for a large number of deaths annually. The major cause of early deaths is ventricular fibrillation. During the past few years, intravenous magnesium has been instituted as a therapy for AMI. This report reviews the latter literature and discusses the potential mechanisms whereby intravenous Mg is beneficial in AMI. Intravenous Mg is a safe and inexpensive drug whose use reduces the incidence of arrhythmias, infarct size and early mortality following AMI. PMID- 2095159 TI - Effects of monoclonal antibody anti-EGF receptor on human nasopharyngeal carcinoma cell and other tumor cells. AB - Three anti-EGF receptor MoAbs were used in these studies. Administration of MoAbs 3 and 176 inhibited tumor formation in nude mice by CNE-2, a poorly differentiated nasopharyngeal carcinoma cell line and A431, an epidermoid carcinoma cell line. When the same MoAbs were used in treatment against HeLa, a cervical carcinoma, tumor growth was not affected. The number of EGF receptors and apparent dissociation constants for 125I-EGF on CNE-2 and A431 was 1.3 x 10(5)/cell (Kd 7.7 x 10(-8) mol/L) and 1.4 x 10(6)/cell (Kd 2.4 x 10(-9) mol/L), respectively. Both MoAbs 3 and 176, capable of competing with EGF for receptor binding, showed significant tumor growth inhibition. MoAb 101 was incapable of blocking the binding of EGF to its receptor, and not as effective as MoAbs 3 and 176 in tumor growth inhibition. Our observation is that the MoAb anti-EGF receptor is cytostatic rather than cytocidal, in vitro against CNE-2 and A431. PMID- 2095161 TI - Endothelium-dependent gender differences in responsiveness of rat aortic smooth muscle to reduction in extracellular magnesium and sodium ions. AB - Possible gender differences in contractile responses to reduction in extracellular Mg2+ ([Mg2+]0) and [Na+]0 in isolated aortic rings and strips from adult rats were investigated. In consonance with our previous studies, [Mg2+]0 withdrawal (0 mM Mg2+) and reduction in [Na2+]0 (total = 84 mM Na+) by replacement of NaCl with isosmolar amounts of sucrose in normal Krebs-Ringer bicarbonate (NKRB) induced significant increases of basal tone of aortic rings and strips in male, but not in female, rats. However, such tension development was observed in endothelium-denuded aortic preparations isolated from both sexes. No effects of indomethacin (10(-5) M) were found in any of the tissues tested. Adding 1.2 mM MgSO4 to the Mg2+ and Na(+)-deficient incubation media relaxed the tension increase to a normal basal level. The endothelium-dependent vasodilator responses to acetylcholine (10(-10) - 10(-6) M) of aortic rings from male or female rats in NKRB were not different. These results suggest that: (1) as in vascular smooth muscle cells, Mg2+ plays an important role in Ca2+ homeostasis in endothelial cells, probably via Na(+)-Ca2+ exchange and (2) sex steroid hormones may influence contractile responses of vascular smooth muscle by modifying endothelium function through such Mg(2+)-regulated internal Na(2+)-dependent Ca2+ entry. PMID- 2095162 TI - Effect of intravenous magnesium sulfate on blood magnesium parameters. AB - Magnesium sulfate was administered intravenously (0.6 mEq/kg body weight over 10 min) to 13 patients with hypertrophic cardiomyopathy undergoing electrophysiologic testing. Total serum, ultrafilterable and protein-bound serum, mononuclear blood cell (MBC) content and concentration, and red blood cell (RBC) concentration of Mg were measured at the following intervals: (1) baseline (before Mg infusion), (2) at the end of infusion, and (3) approximately 40 min after the end of infusion. The total serum, ultrafilterable, and protein-bound fractions rose immediately after infusion and fell by 40 min. The RBC Mg rose and fell less sharply than the serum parameters after Mg infusion. In contrast, the MBC Mg content continued to rise significantly at 40 min after Mg infusion, and MBC concentration showed a continued trend to rise, although this was not statistically significant. PMID- 2095163 TI - Magnesium and potassium administration in acute myocardial infarction. AB - This study included 264 patients with proven acute myocardial infarction who were randomized to either magnesium sulphate, potassium chloride, 10% glucose solution or a placebo containing 200 ml of 2% glucose solution given intravenously, slowly, daily for 3 days in a double-blind, placebo-controlled fashion. The ages varied between 30 and 65 years and 230 were males. Laboratory data such as enzymes, sodium, potassium, calcium and magnesium were obtained in all the patients before and after the therapy. Age, sex, risk factors and drug therapy were comparable between all the groups of patients. After 4 weeks of follow-up, there was a significant decrease in the total number of complications in group A (52%) and B (30%) patients, who were given magnesium and potassium compared to group C and D, who were administered only 10% glucose and placebo. There was a significant rise in mean serum magnesium and potassium levels in group A and B, respectively, after therapy compared to their mean concentrations before therapy. Although mortality was less in groups A and B, a firm statistical conclusion is not possible due to a lesser number of cases. However, it is possible that magnesium and potassium ions have beneficial effects on ischemia-induced alterations and myocardial metabolism resulting in less complications and mortality in group A and B patients. PMID- 2095164 TI - Correlations between ventricular arrhythmias and electrolyte disturbances after acute myocardial infarction. AB - Seven 24-hour ECG recordings and blood samples were taken within 3 weeks in 42 patients who had suffered an acute myocardial infarction (AMI). Ca, K and Mg concentrations in serum, and K and Mg in the erythrocytes, were determined by atomic absorption spectroscopy. One half of the patients were infused with 81 mval/day MgSO4 for 3 days. In patients who exhibited intense electrolyte alterations 10-20 days after AMI, there was a significantly higher rate in the frequency of couplets and/or tachycardia in the 2- to 20-day period after AMI. In patients infused with MgSO4, the fluctuation in serum electrolytes and the rate of arrhythmias were significantly reduced. PMID- 2095165 TI - Can aluminium phosphide poisoning cause hypermagnesaemia? A study of 121 patients. AB - Aluminium phosphide (ALP) poisoning is one of the major causes of death in northern India. It is the commonest mode for suicide. The present study includes 121 patients of proven ALP poisoning. The age varied between 20 and 45 years, and the majority (95) were females. Clinical manifestations were nausea and vomiting in all the patients, dyspnoea and palpitation (78 each), cyanosis (65), hypotension (43) and shock (57). Cardiac arrhythmias were present in 96 cases and hypermagnesaemia in 51 patients. The mean serum total magnesium level (1.94 +/- 0.29 mEq/l) was significantly (p less than 0.01) elevated compared to the mean total magnesium level in control subjects (1.62 +/- 0.26 mEq/l). There was a significantly greater rise in serum magnesium in patients with severe toxicity compared to patients with mild to moderate toxicity. Out of 121 cases studied, 86 died; 76 died within 24 h of ALP ingestion. Mortality was commoner (45 out of 57) in patients with severe toxicity. PMID- 2095166 TI - Effect of vanadium, iodine and their interaction on growth, blood variables, liver trace elements and thyroid status indices in rats. AB - A two-factor, two-by-three factorially arranged experiment was performed to ascertain whether iodine affects the response of rats to vanadium deprivation. Male weanling Wistar-Kyoto rats were fed a 16% casein 68% acid-washed ground corn diet for 8 weeks. The variables were supplemental vanadium at 0 or 1 microgram/g and supplemental iodine at 0, 0.33 or 25 micrograms/g. Vanadium deprivation increased thyroid weight and thyroid weight/body weight ratio and decreased the concentration of vanadium in liver. Vanadium and iodine interacted such that, as dietary iodine was increased, plasma glucose increased in the vanadium-deficient rats but decreased in the vanadium-supplemented rats. Also, as dietary iodine was increased, thyroid peroxidase activity decreased; the decrease was more marked in the vanadium-supplemented than the vanadium-deprived rats. The findings suggest that vanadium may have a physiological role affecting iodine metabolism and thyroid function. PMID- 2095167 TI - Effects of arsenic deprivation in hamsters. AB - An experiment was conducted to ascertain the effects of arsenic deprivation in hamsters. Male weanling Golden Syrian hamsters were fed a casein-corn-based diet containing approximately 12 ng arsenic/g. Controls were fed 1 microgram arsenic/g of diet, as Na2HAsO4.7 H2O. After 6 weeks arsenic deprivation elevated heart weight/body weight ratio and the concentration of liver zinc and decreased the concentrations of the plasma amino acids alanine, glycine, phenylalanine and taurine. Although no biological role has been found for arsenic, the findings indicate that the hamster is a suitable animal for arsenic deprivation studies and support the hypothesis that arsenic may have a physiological role that influences methionine/methyl metabolism. PMID- 2095168 TI - Genetics of lactic acid bacteria with special reference to lactococci. AB - Lactic acid bacteria play an important role in the manufacture of fermented foods. Genetic studies have made these microorganisms, particularly lactococci, accessible to genetic manipulation. The instability of key metabolic traits of lactococci has been explained by the presence of plasmid DNA species. Most genetic interest has been focused to solve the quoted instability and the sensitivity to bacteriophage infection. At the same time, gene transfer systems have been developed and specific genes with commercial significance have been identified and cloned. Lactic acid bacteria can be also used as production organisms of heterologous proteins, e.g. chymosin, lysozyme. PMID- 2095169 TI - [Evolution of the yeast microflora during the first days of fermentation in inoculated Majorcan musts]. AB - Three fermentations were carried out with grape must of the Callet variety. This cultivar is considered autochthonous from the island of Majorca. Two tanks were inoculated with starting cultures of selected yeasts and the last was fermented spontaneously by wild yeasts. The frequency of yeast isolates during the early stages of the fermentation, showed that Candida stellata was more affected by the inoculation than the other wild yeasts with the exception of Saccharomyces cerevisiae. The chemical analyses of wines showed a better alcoholic rate and less volatile acidity in the inoculated wines. Two sensorial analyses were performed and significant differences between the wines were noted. PMID- 2095171 TI - [Approximation of the dynamics of microbial contamination of the Segre River in Lerida]. AB - The water rivers contains a basal autochthonus population of micro-organisms which is local and temporal and it is modified by the incoming sewage. In this paper a simple model is applied to estimate the faecal bacterial load poured from the town of Lerida to the Segre River and the downstream assimilation capacity of this river. In spite of the inherent limitations and imprecision due to sampling operations and calculations, the numerical results are related to other published results. The evolution of faecal bacterial population downstream of Lerida does not follow the theoretical model without a growth coefficient. The showed data on faecal pollution (bacteriological and viral detectors) are the only ones which have been published on the final section, the most disturbed, of the Segre River. PMID- 2095170 TI - Sensitivity to phages of Streptomyces coelicolor strains harbouring type II restriction endonucleases. AB - The role of type II restriction endonucleases in phage development in two different strains of Streptomyces coelicolor has been analyzed. Two of ten phages tested (phi A4 R4c 1) presented a low efficiency of plating (e.o.p.) in the studied strains. The isolation of host-range mutants of phi A4 and R4c 1, with improved e.o.p. and higher adsorption capability in these two bacterial strains, suggests that the presence of host endonucleases is not the main barrier for these phages, but rather adsorption inability. PMID- 2095172 TI - Structure of the DNA of five bacteriophages infecting Micromonospora. AB - The physical maps of the DNA of five bacteriophages (Mm1, OM2, OM3, Mm4 and Mm5) which infect Micromonospora are presented. The restriction analyses showed that all of them had linear, double-stranded DNA, but only four (Mm1, OM2, Mm4 and Mm5) presented cohesive ends. The phages showed no relationship in terms of their restriction maps or of DNA-DNA hybridization, with the exception of Mm4 and Mm5, which resulted to be very similar. Phage Mm5 presented a high level of resistance to chelating agents, although deletion mutants, all of them showing a single detection of 1.4 kb, were obtained by using extremely selective conditions. PMID- 2095173 TI - Endemic pemphigus foliaceus in western Parana, Brazil (1976-1988). Cooperative Group for Fogo Selvagem Research. AB - Endemic pemphigus foliaceus or fogo selvagem (FS) is a blistering autoimmune disease indigenous to certain states of Brazil. In the state of Parana the disease has been reported in the north-central regions where a total of 632 cases were documented in the period of 1940-80. The present study describes a new focus of FS in the western region of the state of Parana. This focus includes a total of 213 new cases of FS and only 11 cases of pemphigus vulgaris seen in this region from February 1976 to July 1988. Over 90% of these patients were peasants working in agriculture or involved in other outdoor activities. PMID- 2095174 TI - The association of bullous pemphigoid and malignant disease: a case control study. AB - In a case control study, the incidence of malignant disease in 84 patients with bullous pemphigoid (BP) was compared with 168 controls. The rate of malignant disease (past, concurrent or during follow-up) in BP patients was 17.9% compared to 5.3% in the controls. A number of the malignancies occurring in the BP group may be of doubtful significance, being either temporally very remote or partially attributable to treatment. The rate of concurrent BP and malignancy (within 8 weeks) was 6.0% suggesting that there is probably a slight excess of malignancy in BP, but insufficient to warrant extensive investigation in pursuit of cancer. Comparison of the BP patients with and without cancer identified no clinical or immunopathological subgroups in whom investigations would be indicated. Three patients with both BP and malignancy were HLA-DR 13 positive, which may point to an immunogenetic predisposition to both diseases. PMID- 2095175 TI - Linear IgA disease of adults: association with lymphoproliferative malignancy and possible role of other triggering factors. AB - Seventy patients with linear IgA disease of adults were followed up for a mean of 8.5 years and all malignant diseases in this group were ascertained. There were three cases of lymphoproliferative malignancy, which constituted a significant excess over the 0.2 cases that would be expected by comparison with an age- and sex-matched population using National Cancer Registry statistics. In contrast, the non-lymphoid malignancy rate of 13% is almost identical to the expected 14%. A subgroup of 35 of the adult linear IgA disease patients were assessed with respect to the possible precipitating illnesses or drugs, as well as co-existing medical conditions. Almost one-third of patients described an event that was felt could possibly have triggered the linear IgA disease, the most frequent being non steroidal anti-inflammatory or antibiotic drug therapy, trauma/burns and upper respiratory tract infections. However, it is difficult to determine how often the preceding event is coincidental, and how often, if at all, it is causal. PMID- 2095176 TI - Chronic urticaria and cancer: an epidemiological study of 1155 patients. AB - To evaluate the possible association of malignant disease with chronic urticaria 1155 consecutive cases with chronic urticaria were reviewed. The Swedish Cancer Registry, Stockholm, was searched for records reporting malignancies in the study population (1958-84), and the expected number of malignancies was calculated on the basis of age- and sex-standardized incidence data. A malignancy was diagnosed in 36 patients with urticaria and the expected number of malignancies was 41. In 23 patients the malignancy appeared during the same year as the onset of urticaria or later. The expected number was 25.6. We conclude that chronic urticaria is not statistically associated with malignancy in general. PMID- 2095177 TI - The effects of an abrasive agent on normal skin and on photoaged skin in comparison with topical tretinoin. AB - Two studies were designed to assess the effect of abrasive preparations on the skin and to test the specificity of the effect of topical tretinoin in the management of chronic photodamage to the skin. In the first study two abrasive preparations (Brasivol fine and Brasivol medium) were compared with white soft paraffin and no treatment in eight volunteer subjects for their effects on the epidermis. The study was conducted over 3 days and measurements were taken of the effects on dansyl chloride-induced fluorescence to assess desquamation, epidermal thickness, and the tritiated thymidine autoradiographic labelling index. The abrasives were found to increase the desquamation rate significantly and to increase epidermal thickness and the epidermal labelling index compared to white soft paraffin and no treatment. In the second study the effect of one of the abrasive preparations (Brasivol medium) was compared with 0.05% tretinoin cream (Retin A) on the photodamaged skin of the dorsal aspects of the forearms of 12 subjects over an 8-week period. Cutaneous blood flow measured by the laser Doppler flowmeter was found to be significantly increased in the abrasive-treated sites, but there was only a non-significant trend to increased blood flow in the tretinoin-treated sites. Measurements of skin thickness using pulsed A-scan ultrasound demonstrated that both treatments produced significant increases in thickness over the 8-week period but the increase was greater for the abrasive treated site. Measurements of the skin extensibility at the treated sites were made using a uniaxial extensometer. Forces needed for 30% skin extension were increased in the abrasive-treated sites only. Measurements of epidermal thickness and of [3H]-thymidine autoradiographic labelling indices showed greater increases in the abrasive-treated sites than in tretinoin-treated sites compared to untreated sites, but these increases were not statistically significant. No significant inflammation and no changes in the degree of elastosis or the presence of a 'repair zone' were found in any of the post-treatment biopsies. The results indicate that some of the changes produced in the skin by topical tretinoin that are taken to indicate a specific antiphotoageing effect may not in fact be specific and can be achieved by an abrasive preparation. PMID- 2095178 TI - Fibroblast-keratinocyte interactions in psoriasis: failure of psoriatic fibroblasts to stimulate keratinocyte proliferation in vitro. AB - We have tested in two ways the hypothesis that dermal fibroblasts direct the hyperproliferation of the overlying epidermis in psoriasis. First, culture medium from psoriatic and from normal skin fibroblasts was added to monolayer cultures of foreskin keratinocytes. Second, psoriatic and normal fibroblasts embedded in hydrated collagen lattices were co-cultured with monolayers of foreskin keratinocytes. There was no evidence in either study that psoriatic fibroblast products could stimulate the proliferation of the keratinocytes, or that normal fibroblast products inhibited their proliferation. A positive control for the fibroblasts was provided by leucocyte supernatants, which stimulated keratinocyte proliferation by up to 65%. Our data do not support a primary role for dermal fibroblasts in psoriasis. PMID- 2095179 TI - Frictional properties of human skin: relation to age, sex and anatomical region, stratum corneum hydration and transepidermal water loss. AB - Differences in the dynamic skin friction coefficients (mu) were investigated with respect to age, sex, and anatomical region. A total of 29 volunteers consisting of seven young females, seven old females, seven young males, and eight old males participated in the study. Measurements were obtained from II anatomical regions, namely, the forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper and lower back, thigh, and ankle. The friction data were compared with stratum corneum hydration and transepidermal water loss (TEWL). The dynamic friction coefficient did not vary significantly between age and sex groups but varied considerably among the anatomical regions of the body. The forehead and postauricular had the highest mu (0.34 +/- 0.02) while the abdomen had the lowest (0.12 +/- 0.01); the remaining regions had an average mu value of 0.21 +/- 0.01. Similarly, no sex differences were observed for TEWL and stratum corneum hydration. Capacitance was only significantly lower on the palms of the elderly. Regional differences showed a higher state of hydration on the forehead and postauricular as well as the upper arm, upper and lower back when compared with the volar forearm. TEWL was generally lower in the elderly on all anatomical regions except the postauricular and palm. A significant correlation was established between mu and capacitance for most regions. Between mu and TEWL significant correlation was observed only on the palm and thigh. These findings suggest that frictional properties of skin are dependent on more than water content or non-apparent sweating and the role of sebum secretion is suggested as one possible factor. PMID- 2095180 TI - Epidermal interleukin 1 in normal skin of patients with HIV infection. AB - Interleukin 1 (IL-1) in the epidermis plays an important role together with Langerhans cells in the activation of the T cells. To determine whether IL-1 could be located in the normal epidermis of 54 patients with HIV infection and related to the stage of the disease, an indirect immunofluorescence technique was used. Intense epidermal fluorescence to IL-1 was noted in the asymptomatic stage II of the disease, whereas there was minimal reactivity in the other stages. PMID- 2095181 TI - Assessment of a contact-plate sampling technique and subsequent quantitative bacterial studies in atopic dermatitis. AB - The aerobic bacterial flora of 20 patients with atopic dermatitis and 19 control subjects was extensively sampled using the Williamson and Kligman scrub technique and a contact-plate method (cysteine lactose electrolyte deficient media). Comparison of the two quantitative techniques showed that the contact plate is a reliable and convenient alternative to the scrub technique for the quantification of Staphylococcus aureus, micrococci and coagulase negative staphylococci. Quantification of bacterial flora using both techniques showed high rates of colonization by S. aureus on both involved and clinically normal skin of patients with atopic dermatitis. A linear increase in S. aureus counts with increasing severity of dermatitis was found. In contrast, diphtheroids showed a trend of decreasing isolation rates and counts as the severity of the dermatitis increased. Isolation rates and absolute counts for micrococci/coagulase negative cocci were unaffected by the severity of the dermatitis. PMID- 2095182 TI - Effect of incisional biopsy on subsequent histology of melanocytic naevi. AB - We examined the effect of incisional biopsy on the subsequent histology of 15 benign melanocytic naevi. In all cases the histology of the residual lesion within the second specimen was unchanged apart from the presence of a surgical scar, and in general the definitive excision specimen showed a reduction in melanocytes at the dermo-epidermal junction overlying the scar. In no case were there any features suggestive of melanoma. PMID- 2095183 TI - Regressing atypical histiocytosis and lymphomatoid papulosis: variants of the same disorder? AB - We report a patient with lymphomatoid papulosis who developed a lesion with the clinicopathological features of regressing atypical histiocytosis. Immunohistochemical studies supported a T-cell histogenesis and many of the atypical cells demonstrated BerH2 (Ki-I antigen) positivity. The case supports the view that regressing atypical histiocytosis and lymphomatoid papulosis are different manifestations of the same disease spectrum. PMID- 2095184 TI - Hereditary woolly hair with ocular involvement. PMID- 2095186 TI - Efficacy of intravenous immunoglobulins in sclerodermatomyositis. PMID- 2095185 TI - Squamous cell carcinoma complicating hidradenitis suppurativa. PMID- 2095187 TI - Commercial assay for steroid sulphatase activity in X-linked ichthyosis. PMID- 2095189 TI - Erosive pustular dermatosis of the leg--a definition. PMID- 2095188 TI - Sunbed pseudoporphyria induced by nalidixic acid. PMID- 2095190 TI - Topical capsaicin for psoriasis. PMID- 2095191 TI - Treatment of lichen planus with a short course of oral prednisolone. PMID- 2095192 TI - Is pemphigus an anti-adhering junction autoimmune disease? PMID- 2095193 TI - Allogeneic cultured epidermal grafts heal chronic ulcers although they do not remain as proved by DNA analysis. AB - To investigate whether allogeneic cultured keratinocytes are rejected or not, and to find out how beneficial their effect on wound healing could be, patients with chronic ulcers were grafted with allogeneic cultured human keratinocytes. In order to examine the epidermal origin of the healed wound, DNA analysis was performed and compared to donor and recipient blood-cell DNA. Healing was observed in 84% of the grafted ulcers by granulation tissue stimulation and would edge effect. In little time 60% of the grafted chronic ulcers healed completely. Although no rejection was observed, DNA analysis revealed that the grafted allogeneic keratinocytes were finally replaced by the patient's own epidermis. This study confirmed that cultured allogeneic keratinocytes that have been grafted on ulcers, play an important role in the wound healing process. PMID- 2095194 TI - Identification of ester glucuronide and sulfate conjugates of 5-hydroxy-6 methoxyindole-2-carboxylic acid and 6-hydroxy-5-methoxyindole-2-carboxylic acid in melanoma urine. AB - HPLC analysis of urine sample from a patient with wide-spread melanoma revealed the presence of unknown indolic compounds at extraordinarily high levels, detectable with electrochemical and/or fluorescent detectors. By enzymic and chemical hydrolyses, they were identified as ester glucuronide and sulfate conjugates of 5-hydroxy-6-methoxyindole-2-carboxylic acid and 6-hydroxy-5 methoxyindole-2-carboxylic acid. Urine samples from B16 melanoma-bearing mice contained the sulfate conjugates but not the ester glucuronide conjugates. PMID- 2095195 TI - Inverse relation between severity of psoriasis and serum 1,25-dihydroxy-vitamin D level. AB - The serum levels of calcium, inorganic phosphate, parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 34 patients with psoriasis vulgaris and compared with the severity of skin lesions. Severity of psoriasis was evaluated by three indices, the area-severity index (ASI), the area index (AI) and the severity index (SI), determined as the product of the area and severity, the area, and the severity of the individual skin lesions, respectively. The mean basal levels of these serum parameters were within the normal range. ASI and SI showed significant inverse correlations (r = 0.387, P less than 0.05 and r = -0.638, P less than 0.01, respectively) with the serum level of 1,25-dihydroxyvitamin D, but not with any other serum parameters, but AI was not correlated with any of these serum parameters. These data suggest that psoriatic patients are not deficient in 1,25-dihydroxyvitamin D, but that development of this skin disease may be related to a slightly decreased level of active metabolites of vitamin D or abnormalities in the responsiveness of the skin cells to them. PMID- 2095196 TI - Purification of antigenic protein of sparganum by immunoaffinity chromatography using a monoclonal antibody. AB - The quality improvement of antigen (crude saline extract) of Spirometra mansoni pleroceroid (sparganum) was investigated by protein purification. The crude extract was fractionated by gel filtration through Sephacryl S-300 Superfine. Its third fraction was purified by affinity chromatography using a monoclonal antibody as ligand. When observed by SDS-PAGE, the purified protein was composed of 2 bands of 36 kDa and 29 kDa which were found already as the most sensitive components in the crude extract by immunoblots with patients sera. The quality of the purified antigen was evaluated in comparison with the crude extract by enzyme linked immunosorbent assay (ELISA) for the specific (IgG) antibody in sera of human sparganosis, other parasitic and neurologic diseases, and normal control. When the purified antigen was used, the sensitivity was not altered but remained high (96.4%) while the specificity was increased from 86.8% to 96.9%. PMID- 2095197 TI - [Cell-mediated immunity in mice infected with Acanthamoeba culbertsoni]. AB - Observations were made on the differences of cell-mediated responses in mice of three infection groups differently scheduled in their severity with pathogenic Acanthamoeba culbertsoni. Infections were done by dropping 5 microliters saline suspension containing 3 x 10(3), 1 x 10(4), or 1 x 10(5) trophozoites, respectively. Amoebae were cultured axenically in CGV medium and inoculated into the right nasal cavity of C3H/HeJ mice aging around 6-8 weeks, under the anesthesia by intraperitoneal injection of secobarbital. Delayed type hypersensitivity (DTH) responses in footpad and blastogenic responses of mouse spleen cells using (3H)-thymidine and the serum antibody titer were measured up to day 14 after infection, and natural killer cell activities were measured up to day 5 after infection. The results obtained in this study were as follows: 1. The mice infected with 3 x 10(3) trophozoites showed mortality rate of 17%, and 34% in the mice infected with 1 x 10(4) trophozoites and 65% with 1 x 10(5) trophozoites. 2. In regard to DTH responses in all experimental groups, the level increased on day 7 and declined on day 14 after infection, but their differences could not be noted between infected and control groups. 3. The blastogenic responses of splenocytes treated with amoeba lysates and lipopolysaccharides (LPS) showed no difference from the control group. The blastogenic responses of splenocytes treated with concanavalin A were declined significantly in the experimental group as compared with the control group, but the blastogenic responses of splenocytes treated with polyinosinic acid were not different from the control group. There was also no difference among three infected groups. 4. The cytotoxic activity of the natural killer cells was activated on day 1 after infection and declined to the level of control group on day 2 in all experimental groups. On day 5 after infection, the natural killer cell cytotoxicity was significantly suppressed as compared with the control groups. 5. The serum antibody titers of the infected mice increased after day 7, but there was no statistical difference between the three infected groups. In summary of the results, there was no difference in cell-mediated immune responses of three experimental groups scheduled with different infection intensities. But there was a significant difference in cell-mediated immune responses between infected and control mice. It is considered that cell-mediated immune responses should be involved in murine model infected with A. culbertsoni. PMID- 2095199 TI - Metacercariae of Pharyngostomum cordatum found from the European grass snake, Rhabdophis tigrina, and its experimental infection to cats. AB - The metacercariae of Pharyngostomum cordatum were found naturally infected in the European grass snake, Rhabdophis tigrina, purchased from a local snake collector in Jinju, Kyongsangnam-do. They were experimentally fed to several kinds of animals such as mice, rats, hamsters, ducklings, a dog, and cats. The adult worms were recovered from the cats 5 weeks after the infection, but none from other animals. The measurements and other morphological characters of the metacercariae and adults were both compatible with those of P. cordatum described by previous authors. The present study confirmed that the snake, Rhabdophis tigrina, serves as a second intermediate (or paratenic) host of P. cordatum in Korea. PMID- 2095198 TI - Experimental life history of Spirometra erinacei. AB - The complete life cycle of Spirometra erinacei has been experimentally maintained in the laboratory. The cyclops were reared as the first intermediate host, and the tadpoles of Rana nigromaculata as the second intermediate host. ICR mice were used as another second host. The experimental definitive hosts were dogs and cats. Maturation and hatching of the eggs took 8 to 14 days by incubation at 29 degrees C. The coracidium measured 43.8 x 36.9 microns. Mesocyclops leuckarti and Eucyclops serrulatus were susceptible to the coracidial infection. The procercoids older than 5 days in the cyclops had minute spines at the anterior end, calcium corpuscles in the body parenchyme and the cercomer at the posterior end. Procercoids 10 to 20 days old were infective to tadpoles, and 15 or 21 day old worms could infect the mice. The plerocercoids from the tadpoles at 15 days after experimental infection were pear-shaped and shorter than 1 mm in the length and were infective to mice. Fifteen to 18 days after experimental inoculation of plerocercoids to dogs or cats, the adult worms began to produce eggs. One life cycle from egg to egg needed 48 to 67 days in the laboratory. The morphology of larval or adult worms was compatible with the description of Spirometra erinacei. PMID- 2095200 TI - [Prophylactic and therapeutic studies on intestinal giant-cystic disease of the Israel carp caused by Thelohanellus kitauei. I. Course of formation and vanishment of the cyst]. AB - In an attempt to develop prophylactic and therapeutic measures of the intestinal giant-cystic disease caused by Thelohanellus kitauei in the Israel carp, Cyprinus carpio nudus, pathological observations were conducted upon the carps which were hatched in May 1988 and raised in a net cage fish farm at the Soyang lake, managed by Horim Fisheries for the period of 21 months with 1-2 months interval. After a gross inspection of the carps, necropsy was carried out periodically in order to clarify the pathological changes in various internal organs and muscular tissues. Also, the prevalence of the disease was checked during the period from 1988 to 1990. Gross inspections revealed that the infected carps showed some degree of fading in body and gill color, back-emaciation symptoms, reddish anus accompanying erosion and relaxation and pot-belly, as well as discharge of yellowish white mucoid material from the anus. However, most carps died eventually of intestinal obstruction. Other significant necropsy findings included cyst formation of various size in the intestinal mucosa, ascites, anemic condition through internal organs and muscular tissues, hyperemia and dilation of intestines with decreased tension, thinness and fragility, and full contents of semi-fluid or yellowish white mucoid material in the intestinal canals. Based on the morphological characteristics of the spores found in the cysts, parasitic location in the intestines, macro- and microscopic findings of the lesions, the parasites were identified as Thelohanellus kitauei Egusa et Nakajima, 1981. Although monthly changes of water temperature were distinct, the extrusion rates of the polar filaments of the spores stayed constant throughout the year with an exception of a lower rate in July. The lesions initiated from mucosa and submucosa in early July became large swellings and then complete mature forms following the peracute course. From late August the upper cysts were gradually opened and most of the spores were dispersed from anus into the surrounding water through December but only a few lasted until next April. The cysts were completely recovered until next September. Comparing the incidence and prevalence of the disease by year tremendous infection and death rates were checked in the first prevalent year, 1988, but the rates were significantly decreased in the second year, and showed an almost normal status in the third year, 1990. As the above summarized results showed, the disease entity might come to an end in three years after the first prevalent year, however, the spores must be strictly prevented because they could be infective in the water for one year. PMID- 2095201 TI - Recent advances with monoclonal antibody drug targeting for the treatment of human cancer. PMID- 2095202 TI - Chemical modifications of proteins: history and applications. PMID- 2095204 TI - Site-directed chemical modification and cross-linking of a monoclonal antibody using equilibrium transfer alkylating cross-link reagents. AB - A new, more reactive group of protein cross-linkers in the class of equilibrium transfer alkylating cross-link (ETAC) reagents has been synthesized. These compounds include alpha,alpha-bis[(p-chlorophenyl)methyl]- and alpha,alpha-bis[(p tolylsulfonyl)methyl]acetophenones substituted in the acetophenone ring with chloro, nitro, amino, and carboxyl groups and derivatives. Included are an 125I labeled ETAC reagent and a 111In-labeled DTPA (diethylenetriaminepentaacetic acid) ETAC for site direction and biodistribution studies. These ETAC compounds were reacted with unreduced and partially reduced antibody under mild pH (pH 4-8) and room temperature conditions to give cross-linked structures. Examination of resultant cross-linked antibody via size-exclusion HPLC, sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, and an enzyme linked immunosorbent assay revealed that (1) both interantibody as well as intraantibody cross-linking had occurred; (2) the level of inter- and intraantibody cross-linking varied with the substituent on the ETAC; (3) the stability of the cross-links on the reducing SDS gels varied with substituents on the ETAC; (4) little if any immunoreactivity was lost after reaction with one of the more effective ETAC cross-linking compounds; (5) the 125I-labeled ETAC sulfhydryl cross-linking in partially reduced antibody increased with pH whereas amine cross-linking with the unreduced antibody decreased with pH; (6) the optimum pH for sulfhydryl site direction was pH 5.0; (7) the 111In DTPA ETAC labeled antibody had a biodistribution in CD1 mice similar to that of the 111In bis cyclic anhydride DTPA labeled antibody. PMID- 2095205 TI - Radiometal labeling of immunoproteins: covalent linkage of 2-(4 isothiocyanatobenzyl)diethylenetriaminepentaacetic acid ligands to immunoglobulin. AB - A study was made of the covalent attachment of the bifunctional 2-(4 isothiocyanatobenzyl)diethylenetriaminetetraacetic acid family of chelate ligands to proteins for the purpose of labeling monoclonal antibodies with radiometals. The parameters and the chemical variables examined included pH, reaction period, temperature, and ligand and protein concentrations. It is shown that these variables, with the exception of protein concentration, have significant effects on the rate of protein conjugation. Conjugation of three monoclonal antibodies and human IgG under identical conditions showed only 17% variation. Finally, the effect of the concentration of conjugated IgG on radiolabeling yield was studied. PMID- 2095203 TI - Preparation and characterization of conjugates of recombinant CD4 and deglycosylated ricin A chain using different cross-linkers. AB - In a previous study, we have demonstrated that conjugates containing soluble, recombinant human CD4 (rCD4) and the deglycosylated form of ricin A chain (dgA) (rCD4-dgA) effectively kill a human T cell line infected with the human immunodeficiency virus (HIV) in vitro. In contrast, such conjugates are 100-1000 fold less toxic to uninfected cells. In order to use a rCD4-dgA conjugate effectively in vivo, it was important to demonstrate that (1) it binds to and kills HIV-infected, but not uninfected, human cells, (2) it is stable in the circulation, and (3) it has an optimal therapeutic index (toxicity to animals versus toxicity to target cells). A major factor affecting the efficacy of such conjugates in vitro and in vivo is the nature of the cross-linker between the ligand (rCD4) and the toxin (dgA). In this report, we have prepared rCD4-dgA conjugates using three different cross-linkers. Different methods of purification have been compared by determining the optimal yield, purity, and retention of biological activity (i.e., binding to gp120 and dgA chain activity). The structure of these conjugates as well as their cytotoxicity to target cells in vitro has been analyzed. Finally, we have compared their pharmacokinetics, tissue localization, and toxicity in mice. PMID- 2095206 TI - Preparation and characterization of paramagnetic polychelates and their protein conjugates. AB - The gadolinium complexes of poly-L-lysine-poly(diethylenetriamine-N,N,N',N",N" pentaacetic acid) (Gd-PL-DTPA) and poly-L-lysine-poly(1,4,7,10 tetraazacyclododecane-N,N',N",N"'-tetr aacetic acid) (Gd-PL-DOTA) and their conjugates with human serum albumin (HSA) have been prepared and characterized. Poly-L-lysine (PL, degree of polymerization approximately 100) was N-acylated with a mixed anhydride of the chelating ligand (DTPA or DOTA). Sixty to ninety chelating groups per molecule of PL could be attached in this way. Following purification of the polychelate by size-exclusion chromatography, the gadolinium complexes were prepared by standard methods and conjugated to HSA with heterobifunctional cross-linking reagents. The molar relaxities of these macromolecular species were 2-3-fold higher than those of the corresponding monomeric metal complexes [( Gd(DTPA)] and [Gd(DOTA)]). The conjugation conditions were optimized to produce conjugates containing 60-90 metal centers per molecule of HSA (ca. one polychelate per protein). PMID- 2095207 TI - Attachment of rhodosaminylanthracyclinone-type anthracyclines to the hinge region of monoclonal antibodies. AB - We have found that a maleimidobenzoyl spacer attached to OH-4' of the rhodosamine moiety of rhodosaminylanthracyclinone-type anthracyclines is most suitable for the attachment of these drugs to carriers, providing important advantages: The spacer is selectively and most readily introduced into the rhodosamine moiety of the drugs, is stable enough for proper handling of the derivatives, and can easily be attached to thiol groups of carrier systems such as reduced monoclonal antibodies. The anthracyclines can be liberated from the conjugates by mere hydrolysis, requiring neither hydrolytic enzymes nor acidic pH. Liberation of the drugs can, moreover, be affected by the presence of the appropriate substituents Z on the phenylene ring of the spacer, thus allowing slowed or enhanced liberation of the cytostatically active drug. The corresponding p maleimidobenzoyl derivatives of beta-rhodomycin I, N,N-dimethyldaunorubicin, and rodorubicin have been attached to thiol groups of the hinge region of reduced monoclonal antibody BW 494/32, directed against a pancreatic cancer associated glycoprotein antigen, resulting in MoAb BW 494/32 conjugates, carrying 4.8-6.8 mol of cytotoxic residues/mol of MoAb. Rodorubicin was similarly attached to MoAb BW 575/931/2, directed against a small cell lung cancer associated antigen and to MoAb BW 431/26, recognizing an epitope detectable on carcinoembryonic antigen. The results provide evidence that the newly developed method of coupling of anthracyclines to the hinge region of monoclonal antibodies may be of broader use. PMID- 2095208 TI - Sequence-targeted photochemical modifications of nucleic acids by complementary oligonucleotides covalently linked to porphyrins. AB - Porphyrins linked to oligonucleotides produce various types of photodamage on a complementary target DNA. The observed reactions include oxidation of guanine bases and cross-linking reactions of the oligonucleotide to its target sequence. Guanines located close to the porphyrin macrocycle were the most altered as compared to more remote guanines on the target sequence. No specific reaction was observed when the complexes were dissociated at temperatures above the melting temperature of the oligonucleotide-target hybrid. Both cross-linking and oxidation reactions accounted for ca. 60% modification of the target chains in the complex. Our results show that oligonucleotides covalently linked to porphyrins are efficient systems for inducing irreversible sequence-specific photodamage on a target DNA. PMID- 2095209 TI - A general method for highly selective cross-linking of unprotected polypeptides via pH-controlled modification of N-terminal alpha-amino groups. AB - A method is described for the highly selective modification of the alpha-amino groups at the N-termini of unprotected peptides to form stable, modified peptide intermediates which can be covalently coupled to other molecules or to a solid support. Acylation with iodoacetic anhydride at pH 6.0 occurs with 90-98% selectivity for the alpha-amino group, depending on the N-terminal residue (as shown with a series of model hexapeptides containing a competing Lys residue). Although Cys residues must be protected (reversibly or irreversibly) before the anhydride reaction, there are no detectable side reactions of the alpha-amino moiety--of the reagent or of modified peptide--with the side chains of His, Met, or Lys. The reaction works well in denaturants, so that inhibitory effects of noncovalent structure can be minimized. In a second step the iodoacetyl-peptide can be reacted with a thiol group on a protein, on a solid chromatography matrix, on a spectroscopic probe, etc. This is illustrated by reaction of a series of N alpha-iodoacetyl-peptides with murine interferon-gamma, which contains a C terminal Cys residue. Data are presented which suggest that this iodoacetic anhydride scheme is superior in selectivity for alpha-amino groups to conventional chemical approaches to cross-linking such as use of 2-iminothiolane or N-hydroxysuccinimide-activated carboxylic acid esters. The reaction is ideally suited for modifying peptide fragments, as pure species or as mixtures, derived from proteolytic or chemical fragmentation of proteins. Furthermore, polypeptides synthesized biosynthetically, for example via recombinant DNA techniques, can be cross-linked in this way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095210 TI - Cleavage of DNA by electrochemically activated MnIII and FeIII complexes of meso tetrakis (N-methyl-4-pyridiniumyl)porphine. AB - Electrochemical methods were used to activate MnIII and FeIII complexes of meso tetrakis(N-methyl-4-pyridiniumyl)porphine (H2TMPyP) to cause cleavage of pBR322 DNA and to study their interaction with sonicated calf thymus DNA. Electrochemical reduction of MnIIITMPyP and FeIIITMPyP (at low concentrations) in the presence of O2 was required to activate these complexes. However, FeIIITMPyP at 1 x 10(-6) M produced DNA strand breakage without being electrochemically reduced. At low concentrations, FeIITMPyP was more efficient at cleaving DNA than MnIITMPyP. Reduction of O2 at a platinum electrode also produced some cleavage but to a much smaller extent. The oxidized form of MnIIITMPyP (charge 5+) has higher affinity for sonicated calf thymus (CT) DNA than the reduced form (charge 4+), as determined by the negative shift in E degrees' for the voltammetric wave in the presence of DNA. Both forms of FeIIITMPyP (charge 4+) interact with DNA to about the same extent. Differential pulse voltammetry was used to determine binding constants (K) and binding-site sizes (s) of the interaction of these metalloporphyrins with sonicated CT DNA. The data were analyzed assuming both mobile and static equilibria. MnIIITMPyP binds to DNA (5 mM Tris, 50 mM NaCl, pH 7) with K = 5 (+/- 2) x 10(6) M-1, s = 3 bp (mobile) or K = 3.6 (+/- 0.3) x 10(6) M-1, s = 4 bp (static). FeIIITMPyP at that ionic strength caused DNA precipitation. At higher ionic strength (0.1 M Tris, 0.1 M NaCl, pH 7), FeIIITMPyP associates to DNA with K = 4.4 (+/- 0.2) x 10(4) M-1, s = 5 bp (mobile) or K = 1.9 (+/- 0.1) x 10(4) M-1, s = 6 bp (static). PMID- 2095211 TI - Synthesis of a diaminedithiol bifunctional chelating agent for incorporation of technetium-99m into biomolecules. AB - The synthesis of a bifunctional chelating agent (BCA), 1, based on the diaminedithiol (DADT) ligand system, is described. The six-step synthetic sequence has been accomplished in 16% overall yield, affording 1, which contains a thiolactone as a reactive moiety, which permits direct coupling to nucleophiles without the formation of byproducts. The reactivity of 1 toward benzylamine and subsequent labeling of the ligand with technetium-99m has been evaluated as a model for preparation of various bioconjugates. Both coupling and exchange labeling occur in high yield under mild conditions, and competition reactions with diethylenetriaminepentaacetic acid (DTPA) indicate the superior stability of the technetium-99m-DADT complex. Preparation of BCA 1 thus provides a new avenue into technetium-labeled radiopharmaceuticals. PMID- 2095212 TI - Evaluation of iodovinyl antibody conjugates: comparison with a p-iodobenzoyl conjugate and direct radioiodination. AB - The preparations and conjugations of 2,3,5,6-tetrafluorophenyl 5-[125I/131I]iodo 4-pentenoate (7a) and 2,3,5,6-tetrafluorophenyl 3,3-dimethyl-5-[125I/131I]iodo-4 pentenoate (7b) to monoclonal antibodies are reported. Reagents 7a and 7b were prepared in high radiochemical yield by iododestannylation of their corresponding 5-tri-n-butylstannyl precursors. Radioiodinated antibody conjugates were prepared by reaction of 7a or 7b with the protein at basic pH. Evaluation of these conjugates by several in vitro procedures demonstrated that the radiolabel was attached to the antibody in a stable manner and that the conjugates maintained immunoreactivity. Comparative dual-isotope biodistribution studies of a monoclonal antibody Fab fragment conjugate of 7a and 7b with the same Fab fragment labeled with N-succinimidyl p-[131I]iodobenzoate (PIB, p-iodobenzoate, 2) or directly radioiodinated have been carried out in tumor-bearing nude mice. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 2 demonstrated that the biodistributions were similar in most organs, except the neck tissue (thyroid-containing) and the stomach, which contained substantially increased levels of the 7a label. Coinjection of the Fab conjugate of 7a with the Fab fragment radioiodinated by using the chloramine-T method demonstrated that the biodistributions were remarkably similar, suggesting roughly equivalent in vivo deiodination of these labeled antibody fragments. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 7b indicated that there was approximately a 2-fold reduction in the amount of in vivo deiodination of the 7b conjugate as compared to the 7a conjugate. PMID- 2095213 TI - The linkage of cytotoxic drugs to monoclonal antibodies for the treatment of cancer. PMID- 2095214 TI - Synthesis of 1-(aminooxy)-4-[(3-nitro-2-pyridyl)dithio]butane and 1-(aminooxy)-4 [(3-nitro-2-pyridyl)dithio]but-2-ene, novel heterobifunctional cross-linking reagents. PMID- 2095216 TI - Neuroendocrine tumors: chromaffin and nonchromaffin tumors. PMID- 2095215 TI - Leukemia: experimental and preclinical studies. PMID- 2095217 TI - Advances in imaging techniques in neuroendocrine tumors: miscellaneous papers of interest. PMID- 2095218 TI - Cancer epidemiology: recent findings. PMID- 2095219 TI - Carcinogenesis. PMID- 2095220 TI - Genetic basis of cancer. PMID- 2095221 TI - Oncogenes: the role of DNA tumor viruses in cancer. PMID- 2095222 TI - Biochemistry of the cancer cell. PMID- 2095223 TI - Cellular properties of cancer. PMID- 2095224 TI - Genetic aspects of metastasis. PMID- 2095225 TI - Leukemia. PMID- 2095226 TI - Pathology and immunology of leukemia. PMID- 2095227 TI - Endocrine tumors. PMID- 2095228 TI - Biology. PMID- 2095229 TI - Cytogenetics and oncogenes. PMID- 2095230 TI - Epidemiology and etiology of leukemia. PMID- 2095231 TI - Acute leukemia in children. PMID- 2095232 TI - Therapy for acute leukemia in adults. PMID- 2095233 TI - Molecular biology and treatment of chronic myelogenous leukemia. PMID- 2095234 TI - Supportive care for patients with acute leukemia. PMID- 2095235 TI - Hematopoietic growth factors. PMID- 2095236 TI - Pituitary tumors. PMID- 2095237 TI - Advances in diagnosing and treating adrenal tumors. PMID- 2095238 TI - Thyroid: diagnostic techniques. PMID- 2095240 TI - Bone marrow transplantation for chronic myelogenous leukemia. PMID- 2095239 TI - Developments in hyperparathyroidism. PMID- 2095241 TI - Autologous bone marrow transplantation in solid tumors. PMID- 2095242 TI - Modern trends in the treatment of multiple myeloma. PMID- 2095244 TI - Early and late complications of bone marrow transplantation. PMID- 2095243 TI - Graft-versus-host disease. PMID- 2095245 TI - Prevention, epidemiology, and prognostic factors in lung cancer. PMID- 2095246 TI - Pleural mesothelioma. PMID- 2095247 TI - Mediastinal tumors. PMID- 2095248 TI - Experimental studies of melanoma and other skin neoplasms. PMID- 2095249 TI - Etiology, epidemiology, and prognosis of melanoma and skin neoplasms. PMID- 2095250 TI - Diagnosis, detection, and staging of cutaneous malignant melanoma. PMID- 2095252 TI - Surgery and radiotherapy for melanoma and skin neoplasms. PMID- 2095251 TI - Melanomas and other skin neoplasms. Chemotherapy and new treatments. PMID- 2095253 TI - Transplantation. PMID- 2095254 TI - Lung and mediastinum. PMID- 2095255 TI - Melanoma and other skin neoplasms. PMID- 2095256 TI - [Infections among drug addicts in Spain: impressions 10 years later]. PMID- 2095257 TI - [In memoriam Dr. Manuel Moreno Lopez]. PMID- 2095258 TI - [The genus Bordetella. By Manuel Moreno Lopez, 1952]. PMID- 2095259 TI - [Evaluation of an immunoenzyme technique for the diagnosis of syphilis]. AB - A comparative study of an enzyme immunoassay (EIA Captia Syphilis Mercia), FTA Abs and VDRL to detect anti-Treponema pallidum antibodies was carried out in overall 290 subjects: 113 had a diagnosis of syphilis (40 primary and 73 secondary) and 117 were controls (40 with nonsyphilitic ulcers, 52 with falsely positive VDRL and 85 healthy subjects). The overall correlations between EIA Captia and FTA and with VDRL were 92% and 72%, respectively. The sensitivity of the method was 82%, with 98% specificity. PMID- 2095260 TI - [Empirical treatment of febrile episodes in patients with neutropenia in bone marrow transplantation]. AB - The results of therapy of febrile episodes during the pregraft phase in bone marrow transplant was retrospectively evaluated in 84 granulocytopenic patients. Most patients received co-trimoxazole and i.v. ticarcillin as antibacterial prophylaxis. 47 episodes were treated with a third generation cephalosporin plus an aminoglycoside, with a 55% favorable response rate. 37 episodes were treated with a wide spectrum penicillin plus an aminoglycoside, with a 41% response rate (p greater than 0.05). Among the 23 infections caused by gram-negative bacilli the response rate was 89% (8 of 9) with the first regimen, and 21% (3 of 14) with the second one (p = 0.003). The investigation of in vitro sensitivity suggested that prophylactic ticarcillin favors the infections due to bacilli with cross resistance to wide spectrum penicillins. The antibiotic regimen did not influence the final resolution or the mortality rate of the febrile episode. PMID- 2095261 TI - [Analysis of urinary infection in the 1st month after kidney transplantation. Value of short prophylaxis with norfloxacin]. AB - Urinary tract infection is the most common complication in the first month after renal transplant, and it is associated with rejection and relapses. In addition, it is the leading cause of gram negative bacilli bacteremia. In a program of continuous epidemiological surveillance from March 1979 to October 1988, we evaluated the urinary tract infections in the first month after renal transplant, considering the following variables: duration of bladder catheterization, urologic complications, type of immunosuppression and preoperative and postoperative antibiotic prophylaxis. There were no differences between the development of urinary tract infections in relation with the duration of bladder catheterization (7 vs 4 days), the reduction of urologic complications (21 vs 6%), or with the introduction of cyclosporin to the conventional immunosuppressive regimen. However, when the group of 46 patients receiving postoperative antibiotic prophylaxis (norfloxacin 800 mg/day every 12 h during the time of vesical catheterization less than or equal to 4 days) was compared with the 147 without postoperative antibiotic prophylaxis, the rate of urinary tract infection in the first month was 8.7% vs 32.8%, respectively (p less than 0.01). Short-term prophylaxis with norfloxacin was a useful regimen, with good oral tolerance and a similar therapeutic efficacy as the sustained regimens reported in the literature. PMID- 2095262 TI - [Comparative study with digoxigenin and biotin markers for the DNA probe identification of genes coding for type TEM beta-lactamases]. AB - We have tested two non-isotopic labels: digoxigenin--11-dUTP and biotin-7-dATP for the detection of TEM-1 beta-lactamase gene with a TEM-1 probe by DNA:DNA hybridisation (using spot technique). The use of radioactive labels is inconvenient and not available to all the clinical bacteriological laboratories. The strains tested were: 16 on file (14 carriers of different types of beta lactamase) and 19 clinical isolated strains. Previously, the plasmid beta lactamase of these strains had been identified by analytical isoelectric focusing. Using the probe labeled with digoxigenin-11-dUTP, the correlation between results obtained by DNA:DNA hybridisation and those by analytical isoelectric focusing was excellent, with no false positives; with the biotin--7 dATP labeled probe, reading was difficult and some false positives were observed. PMID- 2095263 TI - [Native myiasis: report of 2 cases]. AB - Myiasis is a well known conditions among veterinarians, as it causes ravages in cattle. However, in men is at least infrequent, even rare, as judged from the uncommon reports in the literature. We report two cases of human autochthonous myiasis, which can be described as "urban". They appeared in the same geographical area, and flies of the genera Sarcophaga and Lucilia were implicated. PMID- 2095265 TI - [Multicenter study of infectious complications in parenteral drug addicts in Spain: analysis of 11,645 cases (1977-1988). Task Force for the Study of Infections in Drug Addicts]. PMID- 2095264 TI - [Diagnosis of pneumonia caused by Pneumocystis carinii using induced sputum]. AB - Pneumocystis carinii pneumonia is one of the most common and severe infections in patients with human immunodeficiency virus (HIV) infection. Classically, the diagnosis of this condition is made with aggressive techniques such as fibrobronchoscopy (FBS) with bronchoalveolar lavage (BAL) or pulmonary biopsy. Sputum induction is a relatively recent technique which permits the diagnosis in a rapid, inexpensive way which is not aggressive for the patient. We have carried out 22 sputum inductions during a 4 month period. All patients had HIV infection and clinical, radiological and gasometric features consistent with P. carinii pneumonia. P. carinii cysts were found in the BAL of 6 patients and in 4 (66%) of the sputum samples induced from them. These still preliminary data support the need to generalize this procedure to achieve a greater experience in the different institutions, so as to achieve a higher yield of a technique which has clear advantages over previously used ones. PMID- 2095266 TI - [Conjunctival erosion]. PMID- 2095267 TI - [Diarrhea in a drug addict patient]. PMID- 2095268 TI - [Acute respiratory infections in patients with cystic fibrosis: role of viruses and mycoplasmas]. PMID- 2095269 TI - [Diarrhea caused by Aeromonas in Madrid]. PMID- 2095270 TI - [Epidural spinal abscess in a drug addict patient]. PMID- 2095271 TI - [Myopericarditis as the only manifestation of acute toxoplasmosis]. PMID- 2095272 TI - [Inadequate antidiuretic hormone secretion syndrome associated with pulmonary suppuration]. PMID- 2095274 TI - [Muscle enzymes in human trichinosis]. PMID- 2095273 TI - [Enteritis and erythema nodosum caused by Yersinia enterocolitica serogroup 09]. PMID- 2095275 TI - [Pneumonia caused by Mycoplasma pneumoniae: not always a trivial condition]. PMID- 2095276 TI - [Community-acquired pneumococcal meningitis. Report of 11 cases]. PMID- 2095277 TI - [Mitral endocarditis caused by group C beta-hemolytic Streptococcus (S. equisimilis)]. PMID- 2095278 TI - A grading system for lymphocytic plasmacytic colitis in dogs. AB - Colonic mucosal samples were obtained every 4 weeks for 13 months from 6 clinically normal dogs and from 47 dogs with a clinical diagnosis of chronic inflammatory bowel disease. All samples were graded on a scale of 0-5, based upon the quantity of lymphocytes and plasma cells in the lamina propria, epithelial changes, and the presence of ulcers and erosions. A grade of less than or equal to 2.0 was considered normal and was assigned to 77 of 78 samples from clinically normal dogs and 28 of 48 samples from dogs with diarrhea. A transient increase in cellularity was noted in 1 sample from 1 control dog. Nineteen dogs with clinical disease had obvious histologic abnormalities. The grading scheme described provides the pathologist with an objective criterion for the microscopic evaluation of colonic mucosal samples obtained by endoscopic techniques and offers clinicians a method of assessing the dog's progress and response to therapy. PMID- 2095279 TI - Cocklebur toxicosis in cattle associated with the consumption of mature Xanthium strumarium. AB - Cockleburs (Xanthium spp.) are herbaceous annuals with worldwide distribution. Toxicoses are usually associated with the consumption of the seedlings in the cotyledon stage, which contain a high concentration of the toxic principle, carboxyatractyloside. The seeds are also known to contain the toxin, but it has long been assumed that the spiny capsule would deter their consumption. Six of 70 yearling calves died while being fed round bale hay composed predominantly of foxtail and mature cocklebur plants with burs. Clinical signs ranged from acute death to hyperexcitability, blindness, tense musculature, and spastic gaits with heads held high and ears erect. Some symptomatic calves would stumble, fall to lateral recumbency, convulse, and later recover. Overall, the herd was very uneasy. Prominent gross lesions were ascites and a firm, pale liver with a mottled hemorrhagic pattern on cut surface. The rumen contained numerous intact burs and well-ruminated grass. Histological examination of the liver revealed marked centrolobular degeneration and necrosis with associated hemorrhage and congestion. Brain lesions were present. Plant and tissue samples were analyzed for carboxyatractyloside with various results. Samples of rumen contents, urine, and burs contained 100-200 ppm, 0.1-0.05 ppm, and 0.1 ppm, respectively. Based on the history, clinical signs, pathological lesions, and chemical analyses, cocklebur toxicosis associated with consumption of mature Xanthium strumarium in hay was confirmed. PMID- 2095280 TI - A survey of causes of bovine abortion occurring in the San Joaquin Valley, California. AB - The causes of abortion in cattle in the San Joaquin Valley of California were surveyed from submissions to the California Veterinary Diagnostic Laboratory at Tulare. Four hundred sixty-eight abortion cases were examined. Most submissions (89%) were from large drylot dairies, milking an average of 814 cows. Abortion evaluations included necropsy, histopathology, bacteriology, virology, and other immunologic and serologic tests. A specific cause was identified in 29.5% of the abortions. Bacterial infections, most of which were sporadic, accounted for 16% of all abortions. Viral causes and protozoal infections were diagnosed in 5.6% and 3.2% of the abortions, respectively. Fetuses with protozoal infection had histologic lesions of focal nonsuppurative necrotizing encephalitis, and protozoa were detected. Similar histologic lesions were seen in 80 additional fetuses (17.1%), and although an etiologic agent was not identified for these cases, a protozoal infection was suspected. PMID- 2095281 TI - Evaluation of four commercial anaerobic systems for identification of Eubacterium suis. AB - Four commercial anaerobic systems (CASs) were evaluated for usefulness in identification of Eubacterium suis. Twelve strains were evaluated in each system in triplicate, and results were interpreted independently by 5 individuals. Statistically significant differences (P less than 0.01) due to strain variation and reader interpretation accounted for discrepancies encountered. The reactivity, repeatability, and unique profiles generated made both CAS-1 and CAS 2 suitable adjuncts for identification of E. suis when colony morphology and Gram reaction were considered. Limited reactivity in CAS-3 limited its use as an aid in identification. Variability in test observations and the large number of numerical profiles generated precluded use of CAS-4. PMID- 2095282 TI - Evaluation of an enzyme immunoassay for diagnosis of bovine leptospirosis caused by Leptospira interrogans serovar hardjo type hardjo-bovis. AB - Sensitivity and specificity of 4 different antigen preparations from Leptospira interrogans serovar hardjo were compared in an enzyme immunoassay for detection of antibodies against serovar hardjo type hardjo-bovis in serum. Two antigens prepared using detergents showed serogroup cross-reactivity. A mechanically extracted membrane and a lipopolysaccharide antigen showed a high degree of leptospiral serogroup specificity. The lipopolysaccharide antigen was the most suitable antigen for detection of anti-hardjo antibodies. Enzyme immunoassay was more sensitive than the microscopic agglutination test for detecting antibodies in serum from experimentally and naturally infected cattle. It was not possible to differentiate vaccinated from infected animals or to detect a secondary immune response in vaccinated animals that were subsequently infected. PMID- 2095283 TI - Minimal inhibitory concentrations of five antimicrobials against Treponema hyodysenteriae and Treponema innocens. AB - The minimal inhibitory concentrations of carbadox, dimetridazole, lincomycin, ronidazole, and tiamulin against isolates of Treponema hyodysenteriae and Treponema innocens were determined by an agar-dilution method. The results obtained indicated that tiamulin was the most effective antimicrobial in vitro against T. hyodysenteriae, followed by carbadox. Dimetridazole, lincomycin, and ronidazole had poor efficacy in vitro against the T. hyodysenteriae isolates. Isolates of T. innocens were more sensitive to the various antimicrobials. Carbadox and tiamulin were the most effective in vitro, followed by ronidazole, dimetridazole, and lincomycin. PMID- 2095284 TI - Mycoplasma iowae species-specific DNA probe. AB - A Mycoplasma iowae (MI) species-specific DNA probe (designated pMI-2) of 6.0 kbp (kilobase pairs) was isolated from an MI strain I-695 genomic library prepared in plasmid pUC8 and Escherichia coli strain JM83. When labeled with [32]P by nick translation, the probe hybridized in dot blot assays with 6 reference strains and 8 field isolates of MI but not with 16 other known species of avian mycoplasmas. The pMI-2 probe detected a minimum of 1.5 ng of MI strain I-695 chromosomal DNA. Under identical conditions of hybridization, the probe did not hybridize with a high concentration (200 ng) of M. gallisepticum or M. synoviae chromosomal DNA. PMID- 2095285 TI - Gingival vascular hamartoma in three calves. PMID- 2095286 TI - A mycological evaluation and in vivo toxicity evaluation of feed from 41 farms with equine leukoencephalomalacia. PMID- 2095287 TI - Hemoglobin Bart's in a Brazilian black population. AB - Hemoglobin Bart's was measured spectrophotometrically after electrophoresis on cellulose acetate strips in cord blood from 320 full-term randomly selected black newborns from the University Hospital of Campinas, State of Sao Paulo, in the southeast of Brazil. Hb Bart's was detected in 38 of the 320 newborns (11.9%), with the levels presenting the following bimodal distribution: 10.3% of the infants in the 1-3.5% range and 1.6% in the 5-10% range. The data suggest that the frequency of alpha-thalassemia gene in the Brazilian black population is 0.125 since individuals with Bart's Hb in the 5-10% range are usually alpha(+) thalassemia homozygotes. PMID- 2095288 TI - Antiphospholipid antibodies in syphilis. AB - 1. An enzyme-linked immunosorbent assay was used to determine the phospholipid specificity of antibodies present in sera from 35 syphilis patients. 2. Based on the cross-reaction obtained against a mixture of cardiolipin, phosphatidylcholine and cholesterol that is standard for flocculation tests according to the Venereal Disease Research Laboratory (CECON, Sao Paulo, Brazil), all 35 patients tested positive for antibodies of the IgG class whereas 13 (37%) also had IgM antibodies for the same mixture of lipids. IgG antibodies to cardiolipin were demonstrated in 2 patients (6%) and IgM antibodies in 5 (15%). Significant levels of IgG anti phosphatidylcholine were detected in 3 patients (9%) and IgM antibodies in 4 (11%). IgG anti-phosphatidylethanolamine antibodies were found in 1 patient (3%) and IgM antibodies in 3 (9%). Antibody binding to cardiolipin plus cholesterol or cardiolipin plus phosphatidylcholine was as effective as when the standard mixture of all 3 lipids was used. 3. A comparison with serum from systemic lupus erythematosus patients and inhibition studies using liposomes of cardiolipin or the mixture of 3 lipids suggests that there are at least 3 groups of anticardiolipin antibodies. PMID- 2095289 TI - Amniotic fluid lysozyme activity in fetal distress. AB - Lysozyme activity was measured in amniotic fluid samples from 90 pregnant women with gestational age ranging from 30 to 41 weeks. Twenty-nine samples were from high-risk subjects with different pathologies and signs of fetal distress. The control group consisted of 20 normal and 41 pathological pregnant women, whose disorders included Rh isoimmunization, diabetes, systemic arterial hypertension and pre-eclampsia without signs of fetal distress. Amniotic fluid lysozyme levels in normal controls were similar to those detected in abnormal pregnant women without signs of fetal distress (means = 156.0 vs 131.8 micrograms/ml for 34-37 weeks of gestation), with a tendency toward higher values as pregnancy progressed to term (means = 182.1 vs 155.4 micrograms/ml for 38-41 weeks of gestation). Lysozyme levels were significantly lower in high-risk pregnant women with signs of fetal distress, regardless of neonate birth weight, than in subjects showing no such signs (means = 40.3 and means = 25.4 micrograms/ml at 34-37 and 38-41 weeks of gestation, respectively). These data support the possibility of using amniotic fluid lysozyme activity levels as an indicator of fetal distress. PMID- 2095290 TI - Chronic administration of ethanol does not alter plasma kallikrein hepatic clearance. AB - 1. The clearance of plasma kallikrein by the isolated and perfused liver of rats chronically intoxicated with ethanol was studied. Alcohol was added to the diet as 36% of total calories, and the animals were kept on this diet for 5-7 weeks. 2. The hepatic clearance of plasma kallikrein by these rats (uptake half-life, 15 +/- 2 min; N = 3) was similar to that observed in the control groups (normal diet, uptake half-life, 14 +/- 2 min; N = 5, or normal diet with sucrose added as 36% of total calories, uptake half-life, 16 +/- 3 min; N = 4). 3. These results provided indirect evidence that the endocytosis mechanism of plasma kallikrein by the liver differs from that described for glycoproteins which use the galactosyl receptor, since liver endocytosis via this latter system is reduced by chronic alcohol intoxication. PMID- 2095291 TI - Diazepam inhibits retroactive interference of memory in humans: pretreatment with naltrexone does not alter this effect. AB - 1. In a double-blind study of the effects of diazepam and naltrexone on retroactive memory interference, 88 healthy human volunteers were asked to study a text on the 1954 World Soccer Cup and were submitted to a written questionnaire on the material 48 h later. Three hours after reading the text, 58 of the subjects were exposed to a non-factual, derogatory comment on the World Cup. 2. All subjects were given either placebo or naltrexone (50 mg) before reading the text, and either placebo or diazepam (5 mg), per os, 2 h after reading the text (1 h prior to the comment). Subjects were assigned to the different treatment groups by a double-blind design. 3. Exposure to the derogatory comment caused retroactive memory interference with the retention of material from the text. Diazepam blocked the retroactive interference and had no effect of its own on retention of the text. Pretreatment with naltrexone did not influence retention, retrograde interference, or the effect of diazepam on these variables. 4. The results obtained here extend to healthy adult humans observations made on rats and mice in which diazepam blocked retroactive memory interference. PMID- 2095292 TI - Circadian variation of methyleugenol anesthesia in albino rats. AB - In Wistar rats synchronized to a 12-h light/12-h dark cycle (lights on from 08:00 to 20:00 h), the ip injection of methyleugenol (200 mg/kg) at 08:00, 12:00 and 16:00 h significantly increased the sleeping time (time between loss and recovery of righting reflex) when compared to animals anesthetized at 20:00, 24:00 and 04:00 h. These data provide another example of the importance of circadian rhythms in biological systems and their practical relevance to pharmacology. PMID- 2095293 TI - Production of enterotoxin and cytotoxin by Aeromonas veronii. AB - Fourteen strains of Aeromonas veronii were isolated from salt and fresh water in Rio de Janeiro and investigated for the presence of virulence factors. Eleven (79%) A. veronii strains were positive for enterotoxin by the suckling-mouse test and thirteen (93%) produced hemolysin. Of the 13 A. veronii strains that produced hemolysin, seven were investigated for cytotoxin production using Vero cells as indicator cells and all of them were positive. PMID- 2095294 TI - Effect of temperature on the reproduction of the snail Biomphalaria glabrata. AB - 1. The reproduction of the snail Biomphalaria glabrata, one of the intermediate hosts of Schistosoma mansoni, was evaluated under laboratory conditions by measuring egg production, number of ovipositions, number of eggs per oviposition, and hatching rate using a Latin square design with five different temperature treatments. This permitted the elimination of occasional variation in oviposition due to manipulation or a priori group. 2. Egg production and spawning rates were higher at temperatures between 20.0 and 27.5 degrees C than at 17.5 degrees C. Number of eggs per spawning and hatching rate did not vary with temperature. 3. During a 3-day adaptation phase, a short-term thermal effect appeared in which some indices of reproductive rates differed significantly from those of the experimental phase. PMID- 2095295 TI - Morphology and collagen isotypes of carrageenin granuloma. AB - 1. Injection of carrageenin into the liver of rats provoked a focal necrotic hemorrhagic lesion that evolved through acute inflammation, accumulation of macrophages and fibroblasts and the formation of a relatively large amount of fibrous tissue that underwent resorption. The entire lesion disappeared within 15 18 days of the beginning of inoculation. 2. Ultrastructural analysis revealed that carrageenin granules were taken up by macrophages, fibroblasts and myofibroblasts and that signs of formation and degradation of collagen were constant features, the former predominating early and the latter being evident toward the second half of the evolution of the lesion. 3. The presence of fibronectin was prominent during the first days and Type I and Type III collagens were present in the extracellular matrix soon after induction of the carrageenin lesion. Both collagen isotypes subsequently underwent progressive and simultaneous resorption. 4. The rapid formation and degradation of both collagen isotypes during the evolution of carrageenin granuloma indicates that collagen stability is not fundamentally dependent on genetic isotype. PMID- 2095296 TI - Effects of single and long-term administration of sulpiride on open-field and stereotyped behavior of rats. AB - 1. The effects of single (3.0 to 180.0 mg/kg) and long-term (up to 90.0 mg/kg) administration of sulpiride on open-field and apomorphine-induced stereotyped behavior of rats were studied. 2. When animals were studied 30 min after ip sulpiride administration, locomotion and rearing frequencies in the open-field or apomorphine effects were not modified in a dose-dependent and consistent way by the single sulpiride administration. 3. In relation to control values, a significant decrease in apomorphine-induced stereotyped behavior was observed when rats were injected with a single sulpiride dose 2.5, 5.0, 7.5 and 10.0 h before the dopaminergic agonist. 4. Withdrawal from long-term ip sulpiride administration (up to 90.0 mg/kg per injection, twice daily for 57 days) induced a significant increase in all parameters of activity recorded in the open-field, and the responsiveness to apomorphine was also augmented in sulpiride-withdrawn rats. 5. These results suggest that sulpiride, a benzamide drug that differs from classic neuroleptic agents by producing fewer extrapyramidal side effects, also induces supersensitivity of central dopaminergic receptors. PMID- 2095297 TI - Effect of Na+ and Cl- on the velocity of propagation of the spreading depression in chick retina. AB - The chick retina in vitro preparation was used to quantify the effect of Na+ and Cl- on the velocity of propagation of spreading depression (SD). The progressive reduction of chloride concentration in the superfusing Ringer solution, either by partial removal of NaCl or by its partial substitution with isethionate, caused a logarithmic increase in the velocity of propagation of SD. Substituting Tris for Na+ had no appreciable effect on propagation velocity, suggesting that the propagation of the reaction is not necessarily dependent on Na+. However, choline did not substitute for Na+ because it decreased propagation velocity and, at higher concentrations, even blocked the spread of the reaction. PMID- 2095298 TI - Lamina terminalis approach for retrochiasmal craniopharyngiomas. AB - The retrochiasmal location of a tumour and the presence of a prefixed chiasm pose a major difficulty in total excision of craniopharyngiomas. An approach through the lamina terminalis gives direct access to these lesions, which are situated predominantly in the midline. Our experience with total excision of six such tumours exclusively through the lamina terminalis route is presented. Despite a stormy postoperative course due to water and electrolyte imbalance, no mortality resulted and minimal long-term morbidity was observed. Total excision was confirmed in all the cases by postoperative computed tomography scans. PMID- 2095299 TI - Psychobehavioral disturbance in epileptic children. AB - Psychobehavioral disturbances are frequently seen in epileptic children, but they vary in type and degree. This diversity depends on various factors: age at onset, type of epileptic syndrome and EEG pattern, and the drugs used. The early onset of an epileptic process (within the first year of life) has a profound effect on the organization of primary relational processes and on structuring of the ego. The cognitive and behavioral damage that results may become evident after just a few seizures and may persist through time when such damage is not definitive. Epilepsy with onset in childhood may be accompanied by practognosic deficits and impairment of memory, attention and analytical reasoning. These deficits occur much more frequently in the symptomatic forms. In adolescent forms of epilepsy prevalently idiopathic, disturbances of a neurotic type are relatively common. Psychobehavioral disturbances tied to drugs can be noticed mainly with the use of phenobarbital (hyperactivity, longer reaction times), phenytoin (torpor), and politherapy. PMID- 2095301 TI - Advantages and disadvantages of the transcallosal approach to the III ventricle. AB - The advantages of the transcallosal approach used in children during 10 years at the Department of Pediatric Neurosurgery in Prague are: strict midline approach to the III ventricle, sparing both fornices; convenient approach to the left lateral ventricle from a right sided craniotomy. The disadvantages are: neurological sequelae, the most serious of which are mutism and disturbances of recent memory. Older children and those who showed preoperative symptoms of the disconnection syndrome exhibited more deficits after callosotomy. PMID- 2095300 TI - Hyperaminoacidemia in epileptic children treated with valproic acid. AB - Serum amino acids were determined in 22 epileptic children treated with valproic acid. This treatment caused hypocarnitinemia in all, and hyperammonemia in 16. Regardless of the blood ammonia levels, values for glutamic acid, arginine, glycine, serine and alanine were higher than those of normal controls, while aspartic acid and ornithine were lower. These findings suggest that valproate causes intramitochondrial dysfunction of the urea cycle. PMID- 2095302 TI - Mental outcome following encephaloduroarteriosynangiosis in children with moyamoya disease with the onset earlier than 5 years of age. AB - The mental prognosis of children with moyamoya disease, in whom the onset was when they were younger than 5 years of age, has been reported to be very poor. We studied the mental outcome of these patients after encephaloduroarteriosynangiosis (EDAS) in relation to the age at the onset of the disease and the age at operation. For patients in whom the onset of moyamoya disease occurs when they are younger than 2 years of age, the prognosis is very poor with regard to mental abilities even if they have an operation within a year after the onset. Slight hope remains if the operation is within 3 months of the onset. For patients in whom the disease begins when they are 2-5 years of age, EDAS performed before the age of 9 years may result in a good outcome with regard to mental ability, as well as resolution of the paroxysmal symptoms and cerebral revascularization. PMID- 2095303 TI - Management of anterior encephalocele. AB - The authors report their experience with anterior encephalocele, comprising 11 congenital and 11 traumatic cases. Unlike occipital encephaloceles, anterior lesions are usually associated with normal mental development. Surgery aims to restore normal anatomy with repair of the defective dura, bone and skin. Indications, surgical methods and outcome are discussed. PMID- 2095304 TI - Surgical indications for infantile subdural effusion. AB - Thirty-four cases of infantile subdural effusion (ISE) were reviewed in relation to surgical treatment and its prognosis during an average of 4 years of extended follow-up. The surgical indications were determined mainly by the size of the ISE on computed tomography (CT) scan and by metrizamide CT cisternography (MCTC). Consequently, 18 cases were categorized as type A according to MCTC, including 11 cases (61.1%) of ISE CT grade 1. All type A cases were closely observed. This nontreatment regimen yielded excellent results in 15 cases (83.3%). For 10 cases categorized as type B according to MCTC, including 5 cases (50%) of ISE CT grade 3, surgical treatment was indicated and excellent results were obtained in 8 cases (80%). For 6 cases categorized as type C according to MCTC and as ISE CT grade 3, surgery yielded excellent results in 4 cases (66.7%). Antiepileptic drugs have been given to three (27.3%) of the 11 patients who had convulsive attacks. In conclusion, the surgical indications for ISE were based mainly on MCTC in addition to the clinical course, and it is emphasized that, in the early stages, surgery on ISE cases categorized as MCTC types B and C is necessary. PMID- 2095305 TI - A newly designed radiation port for medulloblastoma to prevent metastasis to the cribriform plate region. AB - Nine children with medulloblastoma were treated at Chiba University Hospital from 1977 to 1983. Of these cases, metastases to the cribriform plate region were found in two cases. Portal film showed that cribriform-plate region was not included in a conventional whole-brain radiation port to shield the eyes. Since 1983, we have applied a newly designed radiation port to treat childhood medulloblastoma. The new method consists of two parallel, opposed, lateral ports including the cribriform plate and the first two cervical vertebrae, similar to Pinkel's method. It has been confirmed that this method covers completely the whole brain and is safe for the lens. A characteristic of our method is that the landmark of the lower margin of the radiation port can be easily delineated on the patient's face. We believe that this method contributes to the treatment of medulloblastoma. PMID- 2095306 TI - The use of two-dimensional Doppler sonography (color Doppler) in the diagnosis of hydranencephaly. AB - Hydranencephaly, first described by Cruveilhier, may be defined as a rare condition in which the cerebral hemispheres are replaced by membranous sacs filled with cerebrospinal fluid. Cerebral angiography is especially useful in differentiating hydranencephaly and severe hydrocephalus, massive subdural hygromas and alobar holoprosencephaly, but it is no better than other neuroradiological diagnosis methods in the neonate. This report outlines the diagnostic use of two-dimensional Doppler (color Doppler) in a child with hydranencephaly. Color Doppler was performed using an SSA-270A (Toshiba) with a 3.75 MHz phase-array sector scanning probe and no sedation. In this study, color Doppler demonstrated the internal carotid artery in the proximal portion, but the secondary and tertiary branches were not observed. In summary, color Doppler permitted early, easy diagnosis of hydranencephaly. In addition, the use of color Doppler was beneficial in diagnosing other anomalies of the central nervous system in neonates. PMID- 2095307 TI - Giant congenital meningioma in a newborn. AB - The authors report the case of a giant meningioma in a 5-day-old newborn. Congenital meningiomas are extremely rare. Five newborns with meningiomas have been reported in the literature to date. This is the first case of a newborn with a giant meningioma with supra- and infratentorial and intraorbital components. PMID- 2095308 TI - Neurenteric cysts with meningomyelocele or meningocele. Split notochord syndrome. AB - Two rare cases of neurenteric cysts with meningomyelocele and meningocele were treated. The mechanism of the development of these anomalies is discussed. It is considered that the terminal, dorsal part of the enteric fistula, which is produced between the endoderm and the ectoderm through a partially duplicated notochord in the development of the embryo, remains after obliteration of the fistula and, consequently, that the mucosa of the enteric remnant is inverted and projects through the skin of the back. PMID- 2095309 TI - Intrauterine growing skull fracture. AB - Growing skull fractures with development of leptomeningeal cysts are rare complications of head injuries and have not been described in the perinatal period. The case history of a newborn with bilateral parietal fractures and the formation of a leptomeningeal cyst on one side detected at birth is presented. The importance of radiographic evaluation, including skull films, computered tomography, and magnetic resonance imaging, as well as the associated subarachnoid cyst and the age of presentation are discussed. PMID- 2095310 TI - K(+)-channel openers: new antihypertensive drugs? AB - K(+)-channel openers are a new class of drugs. They interact in a not yet identified fashion with a not yet identified population of K+ channels resulting in an increase in K+ conductance of the surface membrane. K(+)-channel openers have a high affinity for K+ channels of smooth muscle and distinctly less for cardiac or neuronal K+ channels. The cellular effects of K(+)-channel openers in smooth muscle include hyperpolarization, decrease in membrane resistance, inhibition of propagation of excitation, suppression of spontaneous electrical and mechanical activity and inhibition of agonist-induced contraction. The pharmacodynamic profile of K(+)-channel openers is reminiscent of typical vasodilators with decreases in total peripheral resistance and blood pressure and reflex increases in heart rate and cardiac output. While there is no doubt that K(+)-channel openers are effective antihypertensive agents, it is too early, at present, to define their future role in cardiovascular therapy. A satisfactory treatment of hypertension by these drugs may require the addition of diuretics and/or beta-blockers. Other potential clinical indications of K(+)-channel openers include coronary heart disease and asthma. PMID- 2095311 TI - Inhibition of dental plaque formation by mouthwash containing an endo-alpha-1, 3 glucanase. AB - The effect of mouthrinsing with the purified endo-alpha-1, 3 glucanase (mutanase) from a Pseudomonas sp. strain on the formation of dental plaque was investigated. Twenty-two college students participated in the clinical trial. After the labial and lingual surfaces of the 12 front teeth had been subjected to a thorough prophylaxis, the participants were instructed to cease all active oral hygiene practices and to rinse their mouths with either the mutanase or placebo mouthwashes for one minute, up to four times daily, in all, eight times for three days. No restriction regarding meals was given during the experimental period. After a 5-day recess, a second experiment was performed using the same procedures, except the placebo and active mouthwashes were switched. The amount of dental plaque formed on the front teeth was scored according to the criteria of Quigley and Hein. Mean plaque scores were significantly lower for the mutanase (p less than 0.05-0.001) than for the placebo group. In the intraparticipant comparison, most plaque scores were also significantly reduced in general (p less than 0.05-0.0010) by rinsing with the mutanase mouthwash. These data indicate that mutanase is able to suppress the accumulation of dental plaque in humans. PMID- 2095312 TI - Hydrogen peroxide, the effect on plaque and gingivitis when used in an oral irrigator. AB - The identification of plaque as the etiological agent in chronic gingivitis and the progression of chronic periodontitis, has intensified the search for effective chemical antiplaque agents to aid in the prevention and treatment of these diseases. To date, no ideal compound has been identified. Using the experimental gingivitis model, the effectiveness of a 1.5% hydrogen peroxide containing oral rinse, applied as a conventional mouthrinse and in an oral irrigation device, was evaluated. The ability of the mouthrinse to inhibit the development of plaque and gingivitis in the two experimental groups, was compared with controls using a placebo rinse over two 7-day periods. At no time was there any statistical difference between either of the experimental groups and/or the placebo group in terms of gingival or plaque scores. This study concluded that a 1.5% hydrogen peroxide mouthwash was of no therapeutic value in the prevention or treatment of an experimental gingivitis, when used as a mouthrinse or in an oral irrigator. PMID- 2095313 TI - Learning efficiency of a toothbrush for mastering scrubbing method. AB - Toothbrushing with long horizontal strokes often causes traumatization of sound enamel and gingival tissues. Also, dental plaque on cervical and adjacent surfaces of teeth can hardly be removed because toothbrush tips cannot reach these regions adequately. A toothbrushing device which indicates overstroke was tested to determine the efficacy with which it makes subjects master brushing with short horizontal strokes following an initial period of instruction. The degree of learning measured in the testing group was superior to that of the control group immediately after the first instruction. Moreover after one week and 12 weeks, its efficacy persisted. The plaque elimination ratio, however, showed no significant difference between the testing group and the control. PMID- 2095314 TI - Comparative analysis of the plaque removal ability of .007 and .008 toothbrush bristles. AB - A two-phase study was conducted to compare the plaque-removal effectiveness of a .007 toothbrush and a .008 toothbrush when used in an unsupervised home-care program. In the first phase of the study, two children's toothbrushes, a .007 toothbrush (POH Junior #8) and a .008 toothbrush (Allie-Croc), were compared in a population of third through sixth grade children. The .007 group had a greater reduction of plaque from pretest to post-test than the .008 group in all grades, with statistically significant differences favoring the .007 toothbrush for fourth and sixth grades. In phase two a .007 adult toothbrush (POH #4) was compared to a .008 adult toothbrush (Oral B 40) in a population of nursing and dental hygiene students. Both toothbrushes performed equally well with a significant decrease in plaque and gingival inflammation observed from pretest to post-test regardless of toothbrush used. Any changes in soft-tissue abrasion were negligible and not statistically significant. Based on the results of this study, both brushes appear to be safe and effective and can be recommended with confidence. PMID- 2095315 TI - Dentists' and dental hygienists' attitudes toward toothbrush replacement and maintenance. AB - The purpose of this study was to survey dental practitioners regarding their own habits and information provided to their patients on toothbrush replacement and maintenance. Questionnaires were mailed to 717 Chicago-area dentists and dental hygienists with a response rate of 47.5% (n = 341). Results indicate the practitioners recommend their patients replace their toothbrushes usually at three-month intervals when bristles are bent or splayed. This suggested time frame was similar to the interval used by dentists and dental hygienists to discard their own brushes. No particular toothbrush maintenance was routinely recommended, except rinsing the brush and allowing it to air dry. Although practitioners (71-4%) believed the brush was considered a source of microorganisms, most did not suggest soaking the brush in a sanitizing solution. It appears that practicing dentists and dental hygienists may be aware of new research on toothbrush replacement but, for reasons as yet undocumented, this information is not relayed to their patients. PMID- 2095316 TI - In vitro demineralization of enamel by orange juice, apple juice, Pepsi Cola and Diet Pepsi Cola. AB - Enamel demineralization was studied over periods related to normal use of an orange juice, an apple juice, Pepsi Cola and Diet Pepsi Cola. Rectangular blocks of intact human enamel (3 mm x 3 mm) were cut from teeth, coated with nail varnish except for the enamel surface and exposed to the drinks for 2, 4, 5, 6 or 40 minutes. The amount of calcium released from the enamel into solution was determined with the use of an atomic absorption spectrophotometer. The results showed the following degree of enamel demineralization: Pepsi Cola = orange juice greater than apple juice greater than Diet Pepsi Cola. The results suggest that diet colas are less demineralizing than other acid drinks, and complementary plaque studies indicate that they are also less cariogenic. The study emphasized the importance of acid-type, buffer capacity, pH and the presence of other components on the degree of enamel demineralization. PMID- 2095317 TI - Modeling glucose distribution in the cornea. AB - The central cornea obtains its glucose by diffusion through the cornea from the aqueous humor to the epithelium. The diffusion of glucose in the cornea is analogous to the flow of current in an electrical resistance network. The cellular consumption of glucose can be compared to shunting a portion of the charge to electrical ground. An electrical analog model of the cornea was developed to predict the availability of glucose to the epithelium and the distribution of glucose in the stroma. The glucose constant concentration lines in the normal stroma are parallel to the corneal surface and have decreasing values from 880 to 580 micrograms/ml. The effects on epithelial glucose concentration by implanting an intracorneal lens (ICL) of varying diameter, depth, permeability and thickness can be modeled. Glucose permeability through the intracorneal lens has the most significant effect on glucose availability. The ICL profile i.e. power, can also be an important fact in determining glucose availability. A minus power design requires a thin central lens zone with a thick peripheral zone. The design results in relatively more glucose flux through the optical zone of the lens and thus improves central epithelial glucose availability. PMID- 2095318 TI - DNA damage, repair, and replication in selenite-induced cataract in rat lens. AB - DNA synthesis was evaluated in vitro by measuring incorporation of 3H-thymidine in rat lens following systemic delivery of a cataractogenic dose of selenite. Among early metabolic changes observed in the lenses of rats receiving a single dose of 30 nmol Na2SeO3/g body weight was a 30% decrease in DNA replication in lens epithelium occurring between 6 and 12 h after administration of the selenite. This change was followed by an 80% increase in replication by 24 h. Thymidine incorporation in DNA remained elevated compared to controls through 96 h. Unscheduled DNA synthesis was found to be approximately 10% of the total DNA formed, but there was a 30% and 70% increase of this putative DNA repair in the lenses from selenite-treated animals at 6 and 24 h after the injection. Using the alkaline unwinding assay, the proportion of single-strand DNA in lenses from selenite-treated animals increased after 24 h. This estimate of DNA damage was greater in lenses after 96 h. Each component of DNA metabolism: damage, repair, and replication, was affected by the occurrence of selenite stress in lens. These changes both preceded and accompanied nuclear cataract formation. PMID- 2095319 TI - Effects of intravitreal and intravenous administrations of dopamine on the standing potential and the light peak in the intact chicken eye. AB - We studied the modifications of the standing potential (SP) of the eye and of the light peak (LP) after exposure to dopamine, a neurotransmitter released at light by the inner retina and known to affect electrical properties of the retinal pigment epithelium. Intravenous or intravitreal injections of dopamine (DA) were performed on intact chickens. "Choroidal" application (through an intravenous injection) induced a transient increase of the SP and the LP was preserved. On the other hand, "apical" applications of DA (through an intraocular injection) also increased the SP but considerably depressed the LP. These results are in agreement with the hypothesis that the light-induced release of dopamine from the neuroretina may be responsible for the LP generation in the intact chicken eye. PMID- 2095320 TI - Methods for the circumvention of problems associated with the study of the ocular lens plasma membrane-cytoskeleton complex. AB - Two alternative methods for the study of the lens cytoskeleton are described which serve to overcome some of the difficulties imparted by the unique biology of the lens. The first technique involves rapid freezing, thick sectioning, and selective extraction and/or fixation of the lens section. This approach offers several advantages: 1) enhanced visualization of the cytoskeleton, 2) avoidance of fixation gradients, 3) free access for immunocytochemical probes, 4) retention of tissue-wide spatial relationships, with a sharp increase in the resolution of regional analysis, and 5) the capacity for correlative morphological and biochemical comparisons. The second method involves the covalent immobilization of the plasma membrane-cytoskeleton complex (PMCC) to acrylamide beads. This approach permits: 1) avoidance of fixation in the immunocytochemical analysis of lens cytoskeleton and plasma membranes 2) rapid processing of multiple, small quantity samples for immunocytochemistry/biochemical analysis 3) cleaner and more rapid analysis of cytoskeletal extraction conditions. Both approaches, while particularly suited to the study of the lens PMCC, may also be of value to the study of the PMCC of other tissues, particularly where preservation/analysis of regional relationships is essential. PMID- 2095321 TI - Effect of ultraviolet-B radiation on protein synthesis in cultured lens epithelial cells. AB - Exposure of cultured rabbit lens epithelial cells to repetitive doses of UV-B radiation delays their growth and alters the synthesis of specific proteins. Irradiated cells on the shoulder of the survival curve exhibited a dose-dependent decrease in growth when subcultured in serum-supplemented medium. UV-B irradiation did not affect the subsequent attachment efficiency of the cells. Control and UV-B irradiated cells were incubated with [35S]methionine and the pattern of protein synthesis in the cells was analyzed by SDS-PAGE and autoradiography. Analysis of the labeled proteins from cells exposed to UV-B radiation showed the induction of a 32 kD polypeptide and the loss of a 26 kD polypeptide compared with controls. Analysis of the proteins released by the UV-B irradiated cells into the culture medium revealed the 50% loss of a 37 kD radiolabeled protein compared with controls. The alteration of protein synthesis in lens epithelial cells by UV-B radiation may contribute to cataract formation. PMID- 2095322 TI - The role of pneumolysin in ocular infections with Streptococcus pneumoniae. AB - Pneumolysin, a cytolytic protein produced by Streptococcus pneumoniae, has many properties which suggest it may be an important virulence factor in pneumococcal ocular infections. To directly test this possibility, we have constructed pneumolysin-negative strains of S. pneumoniae and compared their virulence with that of the wild type in a rabbit model of intracorneal infection. A pneumolysin negative strain produced by chemical mutagenesis (probably a point mutant) was found to be no less virulent than the parent strain. However, a strain bearing a deletion in the pneumolysin gene showed greatly reduced virulence. This strain produced less pathology while showing significantly higher bacterial counts. These results suggest that a property of the pneumolysin molecule other than its cytolytic (hemolytic) activity may be involved in its pathogenic mechanism of action. This property may be the ability to activate complement, known to be a function of pneumolysin, which results in influx of PMNs, reducing the bacterial counts but also producing tissue damage. PMID- 2095323 TI - Immunocytochemical localization of taurine within glial cells in the optic nerve of adult albino rats. AB - Taurine immunoreactivity in one micron sections of the adult rat optic nerve was observed using light microscopy. Prominent staining was seen in glial cell somata in the perinuclear region and in their processes throughout the nerve, particularly in endfeet on capillaries and in the peripheral basal lamina (glia limitans). Axons and blood vessels showed relatively little or no staining in the mature nerve. The pattern of glial fibrillary acidic protein immunoreactivity on subsequent sections was similar in many respects to that of taurine, suggesting that a sub-population of taurine immunoreactive glial cells are optic nerve astrocytes. PMID- 2095324 TI - The effect of retinoic acid on thymidine incorporation and morphology of corneal stromal fibroblasts. AB - The effect of retinoic acid on DNA synthesis and cell morphology was studied using corneal stromal fibroblasts in culture. All-trans retinoic acid induces an increase in DNA synthesis after 24 hours of exposure. Autoradiographic studies of 3H-thymidine incorporation into corneal stromal cells exposed to 10(-6) M retinoic acid for 24 hours showed an increase in labeling which ranged from 19.2% to 67.6% over control cultures. Scintillation analysis of labeled cultures also showed an increase in incorporation of 3H-thymidine into cells treated with 10( 6) M retinoic acid, with increases ranging from 21.8% to 114.7% above control cultures. Exposure of cultured corneal stromal cells to 10(-6) M retinoic acid resulted in a dramatic change in cell morphology such that they changed from spindle-shaped to round, flattened cells which were epithelioid in appearance. These data demonstrate that biological activity of retinoic acid in stromal fibroblasts and imply a role for vitamin A in maintenance of stroma structure and function. PMID- 2095325 TI - The anterior cruciate ligament. PMID- 2095326 TI - Extruded cervical disc herniation: treatment with anterior microdiscectomy. AB - Nine cases of extruded cervical disc herniation (7 with radiculopathy, 2 with acute myeloradiculopathy) were treated by radical anterior microdiscectomy, with opening of the posterior longitudinal ligament, removal of the extruded peridural disc material, bilateral resection of the posterior part of the uncovertebral joints; in 6 cases surgery was completed with Smith-Robinson intersomatic fusion. In all of the cases symptoms rapidly regressed, with considerable neurological recovery. There were no major complications in any of the cases, and 2-5 years after surgery results were evaluated as excellent in 7 cases and good in 2. The use of the operating microscope allows for removal of extruded disc herniations under magnification, in a bloodless surgical field and with no manipulation of the nervous structures. Because of these features, this method is preferred to traditional posterior surgery and anterior surgery without magnification. PMID- 2095327 TI - The role of surgery in the treatment of localized Ewing's sarcoma. AB - This study includes 193 patients affected with localized Ewing's sarcoma and treated at the Rizzoli Orthopaedic Institute between April 1972 and May 1988. It is the purpose of this study to evaluate the efficacy of surgical treatment with regard to the prognosis of patients affected with E.S. and to define its indications as well as its limits as compared with radiotherapy. Ninety patients were treated surgically: 13 underwent amputation (localization of the disease in the leg and foot), 4 underwent debulking, 48 had resection of the tumor without any reconstruction (expendable bones), while for 25 other patients resection of the tumor required alloplastic or allograft replacement. In cases of E.S. localized in the pelvis and spine, surgery did not obtain improvement in prognosis. In the other sites, the percentage of disease-free patients increased from 57% to 72% in cases where surgery +/- radiotherapy was used instead of radiotherapy alone, while the percentage of local recurrences decreased from 18% to 5.5%, respectively. As for functional results, the highest incidence of excellent to good scores was obtained with surgery associated with radiotherapy (69%). The incidence of complications was only slightly different for the two groups. PMID- 2095328 TI - Osteosynthesis in fractures of the femoral neck in the young adult. AB - The authors report 21 cases of fracture of the femoral neck in the young adult followed-up after a minimum of 2 years, which is a sufficient amount of time to be able to evaluate cephalic necrosis. The results obtained with the various methods of osteosynthesis were: excellent: 38%; good: 33.5%; fair: 9.5%; poor: 19%. Emphasis is made on the effectiveness of the Garden classification system for prognosis and treatment, and several aspects of the method used are discussed. PMID- 2095329 TI - Acute external capsuloligamentous lesions of the knee. AB - The authors discuss 18 cases of acute capsuloligamentous lesions of the external compartment of the knee submitted to surgical treatment. The results obtained by separately studying the progression of the various types of anatomical lesions revealed a relationship between the entity of the lesion and the results. Positive results were as follows: 100% in isolated lesions of the EC, 70% in lesions of the EC and ACL, 40% in lesions of the EC + ACL + PCL. In grade I distorsion trauma surgery is not indicated; in grade II lesions treatment is based on an objective examination in narcosis, and surgery should be performed when dynamic tests are positive; in grade III lesions surgery is always indicated. An objective examination in narcosis (rarely arthroscopy) is thus of essential importance to therapeutic indications. PMID- 2095330 TI - Diagnosis and treatment of popliteal cysts. AB - The authors reviewed 122 patients affected with popliteal cysts and treated between 1975 and 1985 with or without surgery; follow-up ranged from 1 to 7 years (average 3 years and 2 months). The patients were subdivided into 3 age groups, and observed for the clinical, anatomo-pathological and therapeutic differences among them. Cysts affecting children and adults were considered to be acute, or chronic bursitis, and those affecting elderly patients true cysts deriving from the joint cavity. The diagnostic effectiveness of arthrography and sonography is emphasized. PMID- 2095331 TI - Recurrent posterior subluxation of the shoulder. AB - The rare posterior form of instability syndrome of the shoulder is taken into consideration. A diagnostic protocol aimed at revealing posterior slipping of the humeral head following spontaneous movement or with stress is suggested; this involves semiological maneuvers, and the help of radiographs in specific projections and CT scan. As for treatment, the importance of physiatric treatment is emphasized, and surgery advised in young patients who do not benefit from conservative treatment. The authors prefer posterior capsulomyoplasty associated with posterior glenoplasty in forms of the pathology characterized by excessive glenoid retroversion. Finally, 4 personal cases are presented. PMID- 2095332 TI - Supracondylar process of the humerus: four cases. AB - Four cases of supracondylar process of the humerus are presented. Two of the patients were asymptomatic and in one of these the supracondylar process was fractured. In a third there was median nerve compression and in the last there was ulnar nerve entrapment. The anatomical features, clinical symptoms and therapy are described. Good results were obtained after resection of the supracondylar process; neurological symptoms regressed one month after surgery. PMID- 2095334 TI - Quiz. Osteoma. PMID- 2095333 TI - Osteosarcoma associated with Paget's disease: a description of a rare case. AB - Osteosarcoma associated with Paget's disease is very malignant and has an extremely severe prognosis. This is also related to the usually advanced age of the patient and to the consequent impossibility of carrying out suitable chemotherapy. The case presented here is exceptional because of the young age of the patient, which allowed us to use a neoadjuvant chemotherapy protocol. PMID- 2095335 TI - Preferential inhibition of lysosomal beta-mannosidase by sucrose. AB - The lysosomal storage disease beta-mannosidosis, described in both goats and humans, can be detected by measuring a deficiency in hydrolysis of the fluorogenic substrate 4-methylumbelliferyl-beta-D-mannoside. An inhibitor of guinea pig beta-mannosidase (beta-man) activity was detected when tissue was homogenized in phosphate-buffered-saline (pH 7.4) containing 0.25 mol/l sucrose. The existence of such an inhibitor was apparent when the enzyme was immunoprecipitated from tissue using a specific beta-man polyclonal antibody. There was up to a threefold increase in activity in the immunoprecipitated enzyme (antibody-enzyme complex) compared to the activity of the nonimmunoprecipitated enzyme. An extensive study was therefore undertaken to determine the nature and specificity of this inhibitor by analyzing the effect of a range of metal ions and sugars on beta-man activity compared to other lysosomal hydrolase activities. Although ferrous, ferric, cobalt, and manganese ions were highly inhibitory to beta-man, they also inhibited other lysosomal hydrolases to a similar extent. Likewise, mannose inhibited both alpha- and beta-man activities equally. The only compound to specifically inhibit beta-man in a manner similar to that observed in the tissue homogenate was glucosyl(beta, 2)fructofuranoside (sucrose). This is an important finding in that tissue samples are commonly prepared in buffers containing sucrose and this could lead to a wrong diagnosis of beta-man deficiency. In order to determine if the absence of an activator factor or alternatively the presence of a specific inhibitor was a contributing factor in the lack of beta-man activity in cultured fibroblasts from affected humans and goats, mixing studies with normal and affected cell extracts were performed but no restoration or inhibition of beta-man activity was found. PMID- 2095336 TI - Purine synthesis de novo and salvage in hypoxanthine phosphoribosyltransferase deficient mice. AB - Extreme degrees of hypoxanthine phosphoribosyltransferase (HPRT) deficiency in man are associated with gross sex-linked neurological dysfunction, gout and urinary stones (the Lesch-Nyhan or 'complete HPRT-deficiency' syndrome). The less severe degrees of enzyme deficiency (sex-linked recessive gout and/or urolithiasis or the 'partial HPRT-deficiency' syndrome) may be associated with minor neurological manifestations. Whole body purine synthesis de novo is accelerated in both these groups of patients. A strain of mice with an experimentally produced mutation at the HPRT locus showed some residual 'apparent HPRT activity' in brain, liver, testicular, splenic, kidney and ovarian tissues but not in erythrocyte haemolysates. The mutation removes exons 1 and 2 of the coding region of the gene together with the promotor and about 10 kb of upstream sequence from the gene. It is therefore possible that the observed 'apparent HPRT activity' in these mice is due to the operation of an alternative metabolic pathway. Purine synthesis de novo was markedly accelerated in their brain, testicular, splenic and kidney tissues. It was not accelerated in the liver tissue of male mice hemizygous for the mutation and the degree of acceleration in the female homozygotes only just reached statistical significance at the p = 0.02 level. This observation casts doubt on the importance of modulations in the rate of hepatic purine synthesis de novo as a mechanism for maintaining a steady supply of purines for translocation to other organs. PMID- 2095337 TI - Ornithine transcarbamylase deficiency in male adolescence and adulthood. AB - A discrete deficiency of hepatic ornithine transcarbamylase (OTC) was found in male patients who were 58, 46 and 17 years old. Each had developed hyperammonemic coma. The mother and a sister of the 17-year-old patient exhibited orotic aciduria either spontaneously or after protein loading, thus demonstrating heterozygosity. A sister of one other patient and a daughter of the third patient showed a smaller orotic aciduria after protein loading. These observations indicate that inherited deficiency of OTC should be included in the differential diagnosis of hyperammonemic states in adult male patients. PMID- 2095338 TI - The exploration of pharmacokinetic and pharmacodynamic data using interactive three-dimensional graphs, a tool borrowed from particle physics. AB - Computerized interactive 3-dimensional graphical displays were originally developed to aid in the exploration of multidimensional data from particle physics experiments. This technique can be equally well applied to speed the analysis of multivariate pharmaco-kinetic and pharmacodynamic data. The application of this technique to the results of a drug study demonstrated its effectiveness in providing a rapid overview of the data and in displaying new perspectives on the multivariate data, helping to identify sources of variability within the study. Multiple concentration-time curves from a given administration period can be distinguished within a single plot, using visual cues provided by rotating the display. Simultaneous comparison of large numbers of curves allows rapid evaluation of intersubject variability. Comparing the concentration-time curves from a single subject, each in succession, quickly identifies sources of intra-subject variability. Manipulating the display by a fourth dimensional parameter shows the degree of relationship between the concentration-time curves and associated dynamic variables. Exploratory analysis using such kinematic display software, provides a rapid, visually concrete impression of the relationships present in kinetic and dynamic data before the application of standard statistical routines. PMID- 2095339 TI - The haemodynamic effects of long term felodipine therapy in previously untreated essential hypertension. AB - Sixteen patients with previously untreated mild/moderate hypertension (WHO Stage I) were studied: 7 women and 9 men, mean age 56.2 y. Haemodynamics, central and pulmonary blood volumes were measured by radionuclide techniques and repeated after 8 weeks felodipine therapy. To achieve a target diastolic blood pressure of less than 95 mm Hg 12 patients required 5 mg bid, 2 10 mg bid and 1 2.5 mg bid; 1 withdrew after 2 weeks. Mean (SD) arterial blood pressure (mm Hg) was 189/106 before, and 182/103 after 2 weeks placebo treatment and fell to 148/84 after 8 weeks felodipine therapy. Relative systemic vascular resistance fell by 19% from 2146 to 1734 dyn.s.cm-5. There were no significant changes in heart rate, cardiac index, total blood volume, pulmonary blood volume or left ventricular ejection fraction. Plasma renin activity did not rise significantly. Short lived vasodilator side effects occurred in 7/16 patients during initial treatment and mild ankle oedema persisted in 4/16 patients. In contrast to the haemodynamic changes seen acutely with felodipine, the only sustained changes after 8 weeks therapy are reductions in systemic vascular resistance and blood pressure. PMID- 2095340 TI - Package inserts for antihypertensive drugs: use by the patients and impact on adverse drug reactions. AB - In Belgium, all dispensed drugs are provided with package inserts. Traditional physician-orientated inserts are gradually being replaced by patient package inserts (PPIs). The present survey is focused on the use of inserts for antihypertensive drugs and their impact on the reported occurrence and attribution of adverse drug reactions (ADRs). A group of 28 general practitioners (GPs) from the Flemish part of Belgium collected data from 702 hypertensive patients. Each participating GP submitted a consecutive sample of his patients to an interview in the Spring 1989, when 25% of the antihypertensive specialties carried a PPI-version. 1049 prescriptions for antihypertensive drugs had been dispensed. Two thirds of the patients, mostly those with a higher educational level, had read the package inserts. PPIs accounted for 16% of the inserts, and they had not been read significantly more than the traditional inserts. Reporting by the patients of possible drug-related health problems (spontaneously + after having heard the items on a check-list) was not affected by reading the insert or by the type of insert. However, the PPI did bring about spontaneous reporting, especially by patients with a low educational level. Attribution of at least one health problem to the medication was not affected by reading in itself but by the type of insert. Attribution was higher when the patient had received a PPI, except in the case of highly educated patients. Spontaneous reporting and attribution of health problems to the medications prescribed was found more frequently among patients with higher education, who did not seem to need a PPI to recognize problems as being drug-related. PMID- 2095341 TI - Effect of erythromycin on the oro-caecal transit time in man. AB - Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility. 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA.2'-acetyl erythromycin stearate) 800 mg in a double-blind trial. The oro-caecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H2-peak (ppm) in end-expiratory breath by two methods, t1 representing the "front" and t2 the "bulk" of lactulose reaching the colon. t1 was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p less than 0.05, ES vs placebo). t2 was 74 min, 64 min, and 46 min, respectively (p less than 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication. It was concluded that erythromycin shortens the oro-caecal transit time in man and that EA effects the transit time slightly less than ES. PMID- 2095342 TI - Measuring the bronchial effect of bronchodilating drugs in healthy subjects after methacholine provocation. Salbutamol as a model drug. AB - To study whether it would be possible to assess bronchodilating drugs in healthy subjects with methacholine - induced bronchoconstriction, salbutamol 100, 200 and 300 micrograms was inhaled in random order by 12 healthy volunteers in a double blind, placebo-controlled study. Dose response "slope" (DRS = maximum percentage fall in pulmonary function/maximal noncumulative methacholine dose (mumols] was used as an index of bronchial reactivity, and was calculated for forced expiratory flow volume in 1 s (DRSFEV1) and area under the flow-volume curve (DRSAEFV). Bronchial reactivity and its reproducibility were first tested by a standard methacholine provocation method. An abbreviated, single-dose method was used to measure the effect of salbutamol. The reproducibility of methacholine provocation was good, and the single-dose and standard methods gave comparable results. The DRS-values of all the doses of salbutamol differed significantly from placebo and from each other. AEFV did not show any advantage over the FEV1 in this context. A significant negative association between the dose of salbutamol (microgram/kg) and airway reactivity was observed. In conclusion, use of the DRS showed it possible to evaluate the protective efficacy of beta 2 adrenergic agonists against induced bronchoconstriction in healthy subjects. PMID- 2095343 TI - Rapid and slow benzbromarone elimination phenotypes in man: benzbromarone and metabolite profiles. AB - Following oral administration of the uricosuric drug benzbromarone two major metabolites appear in the circulation. 1'-hydroxy-benzbromarone (M1), and a second product (M2) of unknown structure. The plasma concentrations of the parent drug and of M1 and M2 have now been compared in two different elimination phenotypes. 10 subjects who eliminated the drug rapidly (S1-10) and one individual (S11) whose elimination capacity was impaired, presumably due to genetic variation (S11). The AUC (0-96) of the parent drug in S11 was 145 micrograms.ml-1 h. and in the other individuals it averaged 18.3 (11.4-24.5) micrograms.ml-1 h. The plasma elimination half life of benzbromarone was 3.34 (1.77-5.24) h in the rapid eliminators, and 13.08 h in the subject with the elimination defect. The mean plasma elimination half life of the metabolites in S1-10 amounted to 20.1 (11.9-41.2) h for M1, and 17.2 (12.9-30.7) h for M2. In S11 the plasma elimination half life of M1 was prolonged to 76.6 h, and of M2 to 75.4 h. Thus, the elimination defect in S11 was not restricted to the parent drug, but it also involved the two major metabolites M1 and M2. This might be a consequence of a hepatic enzyme deficiency, or be due to impairment of drug excretion. PMID- 2095344 TI - Acute effects on pulmonary haemodynamics of nifedipine in adult patients with cystic fibrosis. AB - Hypoxic pulmonary vasoconstriction is considered to be the primary cause of pulmonary hypertension and cor pulmonale in adult patients with cystic fibrosis (CF). The acute effect on pulmonary haemodynamics of a single sublingual dose of nifedipine 20 mg has been studied in 9 adult patients with CF. Nifedipine significantly attenuated the rise in mean pulmonary artery pressure and pulmonary vascular resistance induced by inhalation of a 13% oxygen gas mix. It also slightly reduced baseline pulmonary artery pressure and pulmonary vascular resistance and lowered pulmonary artery hypertension in the patients. Oxygen delivery was unchanged. Nifedipine is potentially useful for the treatment of hypoxic pulmonary hypertension in patients with CF. PMID- 2095345 TI - Comparison of the diuretic effect and absorption of a single dose of furosemide and free and the fixed combinations of furosemide and triamterene in healthy male adults. AB - The absorption and diuretic effect of furosemide 40 mg alone (F), and of the free (F + T) and the fixed (FT) combinations of furosemide 40 mg and triamterene 50 mg have been compared in 12 healthy young men. A slight reduction in the area under the concentration-time curve (AUC) of plasma furosemide was found for the fixed combination (AUC480) F2.58 micrograms.h.ml-1; F + T 2.46 micrograms.h.ml-1; FT 1.97 micrograms.h.ml-1. There was a significant reduction in the AUC480 of plasma triamterene (F + T 204.9 micrograms.h.l-1; FT 130.2 micrograms.h.l-1). Sodium excretion after F + T and FT was more pronounced than after F (F + T 302 mmol; FT 311 mmol; F259 mmol). When compared to F alone, there was a reduction in the 24 hour potassium excretion after F + T as well as after FT (F 121 mmol; F + T 104 mmol; FT 107 mmol). It is concluded that the absorption of triamterene was significantly reduced after ingestion of the fixed combination tablet. However, in healthy male adults this had no influence on its natriuretic and potassium sparing effect as compared to the free combination. PMID- 2095346 TI - Enhanced elimination of piroxicam by administration of activated charcoal or cholestyramine. AB - This study has compared the effect of repeated administration of charcoal and cholestyramine on the elimination of piroxicam. Eight young adults were given piroxicam as a single dose of 20 mg, on 3 separate occasions. On one of the occasions charcoal was also given. On another occasion cholestyramine was also administered. The mean elimination half-life after piroxicam alone was 53.1 h. This was reduced to 40.0 h by charcoal administration and to 29.6 h after administration of cholestyramine. In the second phase of the study 7 elderly subjects received piroxicam 20 mg for 14 days on two occasions. Cholestyramine administration at the end of one of the periods reduced the mean elimination half life of piroxicam from 52.3 h to 27.3 h. PMID- 2095347 TI - Stereoselectivity of cholinesterase inhibition by galanthamine and tolerance in humans. AB - The effect of galanthamine (GAL) and its 2 major metabolites on human cholinesterases has been explored. Epigalanthamine, a diastereomer of GAL, was 130-times less potent in vitro in its effect on acetylcholinesterase (AChE) in erythrocytes than the parent compound, and it did not differ significantly from the ketone galanthaminone. In vivo, the maximal 36-55% inhibition of AChE was approached 30 min after oral administration of 10 mg GAL. The duration of the catalytic inhibition corresponded to an elimination half-life of approximately 5 7 h. GAL was well tolerated in 8/8 healthy volunteers, and 3/4 Alzheimer patients tolerated the drug up to a daily dose of 40 mg. PMID- 2095348 TI - Ivermectin binds avidly to plasma proteins. AB - Human pharmacokinetic data on the new anti-parasitic agent, ivermectin, are scanty. For the evaluation of its disposition a specific HPLC assay with sensitive fluorescence detection was developed. Applying equilibrium dialysis, plasma protein binding of ivermectin was measured in five healthy individuals and it averaged 93.2 +/- 4.4% (SD). Such strong binding should be taken into consideration, especially in patients with malnutrition or with diseases in which a decrease in plasma proteins and consequently a higher free fraction of ivermectin could be expected. PMID- 2095349 TI - Acetaminophen as a pain enhancer during voluntary interruption of pregnancy with mifepristone and sulprostone. PMID- 2095350 TI - Tricyclic antidepressant plasma level monitoring: intraindividual variability in everyday practice. PMID- 2095351 TI - Clinical implications of slow sulphoxidation of thioridazine in a poor metabolizer of the debrisoquine type. PMID- 2095352 TI - "The only true antiestrogen is no estrogen". PMID- 2095353 TI - Expression of cytochrome P-450(17) alpha, 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase, and steroid 5 alpha-reductase in rat H540 Leydig tumor cells. AB - The rat H540 Leydig tumor cell is established as a model for acute lutropin action on the initial step of steroidogenesis, namely the conversion of cholesterol to pregnenolone. Herein, we demonstrate that H540 cells express high levels of three steroid-metabolizing enzymes which are involved in the further processing of pregnenolone in the endoplasmic reticulum of the steroidogenic cell. In particular, in addition to expressing 17 alpha-hydroxylase cytochrome P 450 (P-450(17) alpha) and 3 beta-hydroxysteroid dehydrogenase/delta 5----4 isomerase (3 beta-HSD), H540 cells also showed high levels of steroid 5 alpha reductase mRNA and activity. The H540 cells therefore exhibit similarity to Leydig cells from sexually immature animals which also demonstrate high 5 alpha reductase activity. Thus, after 3 beta-HSD-catalyzed formation from pregnenolone, progesterone was efficiently converted to 5 alpha-pregnan-3,20-dione (5 alpha dihydroprogesterone) and subsequent metabolism to the corresponding 17 alpha hydroxylated derivative and 5 alpha-androstan-3,17-dione in a reaction catalyzed by P-450(17) alpha. H540 cells have apparently very low 17-ketosteroid reductase activity and, therefore, a principal end-product of the steroidogenic pathway in these cells was 5 alpha-androstan-3,17-dione. H540 cells maintained in primary culture under serum-free conditions accumulated demonstrable levels of mRNA species for P-540 17 alpha (1.7 kb), 3 beta-HSD (1.6 kb) and 5 alpha-reductase (2.7 kb). This finding suggests that the H540 tumor cell model will not only be of utility in the study of acute lutropin action but also in the elucidation of mechanisms involved in the regulation of expression of various families of microsomal steroid-metabolizing enzymes. PMID- 2095354 TI - Sequence-specific binding of androgen-receptor complexes to prostatic binding protein genes. AB - Prostatic binding protein is a complex glycoprotein comprising three components, C1, C2 and C3, organized into two different heterodimers (C1-C3 and C2-C3). The rat ventral prostate genes encoding all three constituent polypeptides are expressed under androgenic control. Analysis of genomic fragments containing the genes and flanking sequences revealed in each case one androgen receptor-binding region upstream of or within the promoter and another in the first intron. The effect of androgens on the expression of these genes may, therefore, be mediated by these direct receptor-DNA interactions. The genomic fragments which contain androgen receptor-binding regions all contain nucleotide sequences reminiscent of glucocorticoid response elements (GRE). Mutations in these sequences in restriction fragments and in synthetic oligonucleotides significantly decreased their affinity for androgen-receptor complexes and their introduction into nonspecific sequences conferred affinity for androgen-receptor complexes. Based on these data, a consensus sequence for putative androgen response elements (ARE) is proposed. However, despite the specific recognition of these sequences by the androgen receptor in vitro, only the C3(1) intronic fragment could confer significant androgen responsiveness on a heterologous promoter. While this could be due to the fact that the GRE-like sequences present in the other fragments are not strong AREs, alternative hypotheses are being investigated currently. Not least of these is that the similar localization of the binding sites in each gene might underlie a more complex androgen regulation mechanism. PMID- 2095355 TI - Interleukin 1 regulates the expression of osteopontin mRNA by osteoblasts. AB - Osteopontin is a matrix protein which belongs to the integrin superfamily and is involved in cell adhesion. In the present study, we examined the regulation of the mRNA expression of osteopontin by interleukin 1 alpha (IL-1 alpha) in osteoblasts. IL-1 alpha greatly increased the steady-state level of osteopontin mRNA in both a mouse osteoblastic cell line (MC3T3-E1) and mouse primary osteoblast-like cells. The increase in the osteopontin mRNA expression by IL-1 alpha was dose-dependent at a range of 0.004-0.2 nM. This was most likely due to an increase in the transcriptional rate, not to an increase in the stability of osteopontin mRNA. The in vitro nuclear transcription experiment showed that IL-1 alpha-treated MC3T3-E1 cells increased the synthesis of osteopontin mRNA. Besides IL-1 alpha, tumor necrosis factor alpha (TNF-alpha), lipopolysaccharides (LPS) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) increased the osteopontin mRNA expression in both the clonal osteoblasts (MC3T3-E1) and the primary osteoblast-like cells. In response to such bone-resorbing agents, primary osteoblast-like cells expressed osteopontin mRNA much more strongly than primary fibroblast-like cells isolated from mouse calvaria. Both IL-1 alpha and 1 alpha,25(OH)2D3 greatly increased the production of 68 and 62 kDa phosphoproteins in conditioned media of MC3T3-E1 cell cultures, which probably correspond to osteopontin. These results suggest that osteopontin plays an important role in bone remodeling, in particular bone resorption. PMID- 2095356 TI - Impaired glucose tolerance in patients with polycystic ovary syndrome (PCOS). AB - Fasting insulin concentration and the insulin response to an oral glucose tolerance test were measured in 15 women with polycystic ovary syndrome (PCOS) and 6 weight-matched normal women. The fasting insulin concentrations were not increased in PCOS in comparison to normal women. Insulin response to an oral glucose test was significantly decreased (p less than 0.05) in PCOS at 30 min, although 63% of these women had mild impairment of glucose tolerance. The glucose response did not differ between the obese PCOS patients and those with nonobesity. No correlations were demonstrated between the fasting serum insulin concentrations and insulin response at 30 min, and both androgens and the luteinizing hormone. These findings suggest that (1) hyperinsulinemia is not a feature of PCOS in Japan; (2) only obese PCOS patients have a tendency of abnormalities in insulin secretion; (3) it is evident that PCOS represents an inadequately characterized disorder of insulin action and a novel paradigm in which to investigate the relationship between reproductive functions and carbohydrate metabolism. PMID- 2095358 TI - Pathophysiology of polycystic ovary syndrome. Overview. PMID- 2095357 TI - A syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans associated with polycystic ovary syndrome: clinical and laboratory features. AB - We describe an adolescent Japanese girl with acanthosis nigricans and irregular anovulatory menstruation following menarche. Serum LH levels were elevated, whereas serum FSH levels were within normal range. An exaggerated response to LHRH was observed. Further, serum androstenedione levels were markedly elevated. Ultrasonogram revealed bilateral polycystic changes of ovaries. She had a mild degree of insulin resistance. Insulin binding studies using erythrocytes demonstrated a decreased binding capacity of insulin. From the above findings, this patient presents the syndrome consisting of hyperandrogenism, insulin resistance, and acanthosis nigricans and also has clinical and biochemical features compatible with polycystic ovary syndrome. PMID- 2095359 TI - Treatment of polycystic ovary syndrome: an overview. PMID- 2095360 TI - Use of hamycin in sterilization of aortic homograft valves. PMID- 2095361 TI - Microbial production of L-phenylalanine: a review. AB - Microbial production of L-phenylalanine by direct fermentation and by substrate conversion has been reviewed. The review also includes a discussion on different other methods for phenylalanine production, their advantages and disadvantages with mutants and genetically tailored strains. Biosynthesis of phenylalanine, its regulation in hyperproducing strains and recovery of phenylalanine has been discussed in brief. PMID- 2095362 TI - Antifungal activity of some phenolic compounds on Fusarium oxysporum f. sp. psidii causing guava wilt. PMID- 2095363 TI - Fungitoxicity of some pesticides against Fusarium udum, the wilt causing organism of pigeon-pea. PMID- 2095364 TI - Antibiotics literature index--a select bibliography. PMID- 2095365 TI - Management of polyamine pools and the regulation of ornithine decarboxylase. AB - The management of polyamine synthesis and polyamine pools differs fundamentally from that of most other small molecular-weight endproducts. The polyamines are vital to growth and important cellular functions, but they are toxic in excess. I argue here that their multivalent cationic character, leading to binding to cell constituents, precludes fluent feedback inhibition of synthesis. This has led to the development of elaborate alternative regulatory mechanisms controlling ornithine decarboxylase, the key initial enzyme of the pathway. Poorly regulated polyamine synthesis and the toxicity of polyamines impose upon cells a need to control uptake and to dispose of excess polyamines. Recent data on polyamine transport suggest unorthodox mechanisms of accomplishing these functions. PMID- 2095366 TI - Characterization of the role of melanoma growth stimulatory activity (MGSA) in the growth of normal melanocytes, nevocytes, and malignant melanocytes. AB - Melanoma growth stimulatory activity (MGSA) was originally described as an endogenous growth factor for human melanoma cells. To test the hypothesis that an MGSA autocrine loop is responsible for the partial freedom from growth control observed in nevocytes and melanoma cells, MGSA growth response and MGSA mRNA/protein levels were examined in these cells compared with normal melanocytes. As a single agent, or in combination with other factors, MGSA stimulated the growth of normal human epidermal melanocytes as well as other growth promoters for melanocytes. Nevocytes were not as responsive to exogenous MGSA as melanocytes. MGSA mRNA was minimal or not detected in cultured normal melanocytes, although the protein was present when the cells were cultured in the presence of serum/growth factors and absent when serum/growth factors were omitted. In contrast, MGSA mRNA was constitutively expressed in the absence of exogenous growth factors in cultures established from benign intradermal and dysplastic nevi and melanoma lesions in different stages of tumor progression. Nevus cultures contained immunoreactive MGSA protein in the presence of serum but were negative or only faintly positive in the absence of serum. Melanoma cell lines were positive for MGSA protein in both the presence and the absence of serum. Thus, continued expression of both MGSA mRNA and MGSA protein in the absence of exogenous hormones or serum factors may correlate with partial freedom from growth control exhibited by malignant melanocytes. PMID- 2095367 TI - Characterization and partial purification of human epithelial transforming growth factor. AB - A polypeptide growth factor has been partially purified from medium conditioned by the human adrenocortical carcinoma cell line SW13. This factor, designated h TGFe, stimulates anchorage-independent growth of the SW13 cells. Similar activity was observed in human milk, and in conditioned media from seven of 14 epithelial cell lines. The SW13-derived activity is stable to low pH and 8M urea but labile to dithiothreitol and 2% sodium dodecyl sulfate. Human TGFe does not bind to heparin and fails to stimulate growth of endothelial cells in monolayer culture. The apparent molecular weight of h-TGFe is 59k by size exclusion chromatography in the presence of 8M urea and the activity binds strongly to cation exchangers. The activity elutes at 15-30% acetonitrile from a C18 reverse-phase column and has been partially purified by using a four-step chromatographic procedure. TGFe appears to be a novel growth factor produced by many epithelial cells and tissues. PMID- 2095368 TI - Detection and localization of actin mRNA isoforms in chicken muscle cells by in situ hybridization using biotinated oligonucleotide probes. AB - We have developed in situ hybridization methodology for nonisotopically labeled oligonucleotide probes to detect cellular mRNA with improved speed, convenience, and resolution over previous techniques. Previous work using isotopically labeled oligonucleotide probes characterized important parameters for in situ hybridization (Anal Biochem 166:389, 1987). Eleven oligonucleotide probes were made to coding and noncoding regions of chick beta-actin mRNA and one oligonucleotide probe to chick alpha-cardiac actin mRNA. All the probes were 3' end-labeled with bio-11-dUTP using terminal transferase, and the labeled probes were hybridized to chicken myoblast and myotube cultures. The hybridized probe was detected using a streptavidin-alkaline phosphatase conjugate. Our assay for the success of probe hybridization and detection was the demonstration of beta actin mRNA highly localized in the lamellipodia of single cells (Lawrence and Singer, Cell 45:407, 1986) as well as the expression of alpha-cardiac actin mRNA and the repression of beta-actin mRNA in differentiating myoblasts and in myotubes. With the alpha-cardiac probe, we found that this mRNA was distributed all over the cytoplasm of myotubes and differentiated (bipolar) single cells and negative in undifferentiated single cells and at the ends of myotubes. When beta actin probes were used, two of 11 probes were highly sensitive, and, in pooling them together, the localization of beta-actin mRNA in fibroblastic single cells was evident at the leading edge of the motile cells, the lamellipodium. beta Actin mRNA was not detected in myotubes except at the ends where contact was made with substrate. This indicates that both beta and cardiac actin mRNA can coexist in the same myotube cytoplasm but at different locations. PMID- 2095369 TI - Characterization of anti-sticking factor-II from goat epididymal plasma. AB - A previous study has characterized the major 47 kDa anti-sticking factor (ASF-I) from goat cauda-epididymal plasma (Roy, N., and Majumder, G.C., Biochim. Biophys. Acta, 991:114-122, 1989). This study reports the purification and characterization of ASF-II, another anti-sticking factor from the goat epididymal plasma. ASF-II was purified to apparent homogeneity by using concanavalin A agarose affinity chromatography, DEAE-cellulose chromatography, alumina gel adsorption, and isoelectric focussing techniques. It showed a single protein band by both non-denaturing and SDS-polyacrylamide gel electrophoresis. ASF-II showed a molecular weight of 36,000 and a sedimentation constant of 2.4S. ASF-II is largely stable to heat treatment and it is a specific glycoprotein having high affinity and specificity for its anti-sticking action. At saturating concentration (1 nM) it inhibited adhesion of nearly 50% of spermatozoa to the glass surface of the haemocytometer counting chamber. Both the protein and sugar parts of the factor are essential for the anti-sticking activity since it lost its activity completely when treated with trypsin, L-fucosidase, or mannosidase. ASF-II does not coat the glass surface and it binds to spermatozoa. Data are consistent with the view that ASF-II has not been derived from the larger ASF-I molecule due to its enzymic modifications. Both ASF-I and -II had no effect on sperm forward motility as evidenced by spectrophotometric motility assays, indicating thereby the suitability of the factors to improve the existing sperm motility assays by eliminating the possibility of cell-sticking artifacts. PMID- 2095370 TI - Partial synthesis and antitubulin activity of minor colchicum alkaloids: N acetoacetyl-deacetylcolchicine and 2-demethylspeciosine (speciocolchine). AB - Two minor Colchicum alkaloids, N-acetoacetyl-deacetylcolchicine [1] and 2 demethylspeciosine [7], were synthesized. The diacetate 8 of 2-demethylspeciosine was also prepared. The antitubulin activity of these compounds, in comparison to colchicine, was measured. N-Acetoacetyl-deacetylcolchicine [1] has in vitro activity similar to that of colchicine. Both 2-demethylspeciosine [7] and the diacetate 8 were considerably less potent inhibitors of tubulin polymerization. PMID- 2095371 TI - Lissoclinolide, the first non-nitrogenous metabolite from a Lissoclinum tunicate. AB - The isolation and characterization of a new metabolite from the tunicate Lissoclinum patella is described. The structure of lissoclinolide [1] was solved using spectral and chemical methods, and it is shown to be the first non nitrogenous, non-sulfur-containing compound to be isolated from the genus Lissoclinum. PMID- 2095372 TI - Antitumor agents, 116. Cytotoxic triterpenes from Maytenus diversifolia. AB - The known triterpenes 3-oxofriedelan-29-oic acid [1], 3-oxofriedelan-28-oic acid [2], and 28,29-dihydroxyfriedelan-3-one [3] have been isolated from Maytenus diversifolia. Compounds 1-3 demonstrated cytotoxicity against the A-549 lung carcinoma cells with ED50 values of 0.21, 1.18, and 0.64 micrograms/ml, respectively. PMID- 2095373 TI - Bioactive compounds from aquatic and terrestrial sources. AB - The world of nature provides a never-ending set of fascinating problems for the chemist. Many of the most intriguing problems, however, concern compounds available in only truly minute quantities. One solution is to focus on bioassay guided separations. In so doing one can isolate compounds with novel structures or unsuspected activities from almost any phylum, including tunicates, sponges, insects, or even the much-studied terrestrial plants, as exemplified in several recent studies in our laboratory involving activities ranging from antiviral and antimicrobial activity to cytotoxicity and immunomodulation. Moreover, newer spectroscopic techniques, especially fast atom bombardment mass spectrometry and tandem mass spectrometry, enhance one's ability to study compounds present in minute quantities, including those of importance to the host organism, such as neuropeptides in insects or marine invertebrates. PMID- 2095374 TI - The gastric cytoprotective effect of several sesquiterpene lactones. AB - The aerial part of Artemisia douglasiana, used in folk medicine as a cytoprotective agent against the development of peptic ulcer, was studied, its active principle dehydroleucodine [1] isolated, and its pharmacological properties analyzed. In order to establish whether or not the reported activity is particular to sesquiterpene lactones, the study of the cytoprotective activity of several related guaianolides and pseudoguaianolides from plants was undertaken. Ludartin [3], 8-angeloyloxy-3-hydroxyguaia-3(15),10(14),11(13)-trien 6,12- olide [4], hymenin [5], mexicanin I [6], helenanin [7], and 9-O desacetylsparthulin-2-O-angelate [8] were found to exhibit protection. Desacetoxymatricarin [2] did not show cytoprotective activity. The results obtained from the different sesquiterpene lactones studied suggest that the presence of the alpha-methylene-gamma-lactone moiety is, in principle, a requirement for the observed antiulcerogenic activity. PMID- 2095375 TI - Antitumor agents, 115. Seselidiol, a new cytotoxic polyacetylene from Seseli mairei. AB - Seselidiol [1], a new polyacetylene, has been isolated from the roots of Seseli mairei. On the basis of chemical and spectroscopic evidence, its structure has been established as heptadeca-1,8(Z)-diene-4,6-diyne-3,10-diol. Seselidiol and its acetate have been demonstrated to show moderate cytotoxicity against KB, P 388, and L-1210 tumor cells. PMID- 2095378 TI - Proceedings of the 13th scientific meeting of the International Society of Hypertension. 24-29 June 1990, Montreal, Canada. PMID- 2095376 TI - 2-O-alpha-D-galactopyranosyl glycerol hexaacetate from Ruellia brittoniana. AB - An extract of the whole plant of Ruellia brittoniana has afforded the new glycoside 2-O-alpha-D-galactopyranosyl glycerol hexaacetate [1]. Its structure and absolute configuration were deduced by spectroscopic methods and X-ray crystallographic analysis. PMID- 2095377 TI - Ambulatory blood pressure monitoring: research and clinical applications. AB - Intra-arterial ambulatory blood pressure monitoring has shown that blood pressure undergoes a marked fall during sleep and marked repeated rises during emotional stimuli, including those elicited when blood pressure is assessed by the physician. This leads to an overestimate of blood pressure levels, which is so variable between patients, and so persistent and unpredictable that it seriously interferes with the diagnosis of hypertension. The ambulatory measurement technique has shown that, to a substantial degree, 24-h blood pressure variations can be attributed to neural influences triggered by environmental stimuli. However, blood pressure oscillates at different frequencies throughout the day and night and thus the overall blood pressure variability can be divided into a non-rhythmic and a rhythmic component, its size in each individual being buffered by the arterial baroreflex. In the light of these findings, ambulatory blood pressure monitoring is not only an important tool in cardiovascular research but also has potential for improving the diagnosis of hypertension and the evaluation of antihypertensive treatment. Ambulatory blood pressure data can be correlated, to a greater degree than clinic blood pressure, with the target-organ damage sustained by both treated and untreated hypertensive patients. However, widespread use of this approach in clinical practice must await the establishment of ambulatory blood pressure norms and demonstration of its prognostic superiority over traditional blood pressure assessments. Further, non-invasive ambulatory blood pressure monitoring (the only approach feasible on a routine basis) has limited accuracy and markedly increases the cost of dealing with hypertension. PMID- 2095379 TI - Hypertension and the arterial system: clinical and therapeutic aspects. AB - There is very clear evidence that active changes in the arterial wall contribute substantially to the pathophysiology, prognosis and treatment of hypertension. Reduced aortic compliance independently affects the blood pressure through an increase in systolic pressure and a decrease in diastolic pressure at any given mean arterial pressure. With the subsequent increase in pulse pressure, arterial abnormalities may specifically influence cardiac morbidity and mortality, in particular by triggering coronary ischemic accidents. The pathophysiological and epidemiological results of these mechanisms clearly indicate that a severe decrease in diastolic blood pressure might precede some hypertensive coronary ischemic accidents. PMID- 2095380 TI - Circadian blood pressure variations under different pathophysiological conditions. AB - The daily variation in blood pressure (circadian blood pressure rhythm) is characterized by a nocturnal fall and a diurnal rise. The circadian blood pressure rhythm seems to be mediated mainly by the circadian rhythm of sympathetic tone, linked to changes in physical and mental activities, e.g. the waking-sleeping cycle. Statistically significant circadian blood pressure rhythms have been confirmed in approximately 80% of mild to moderate essential hypertensive patients as well as in normal subjects. However, the normal pattern of circadian blood pressure rhythm is reversed in elderly people and in those with Cushing's syndrome, those undergoing glucocorticoid treatment, and those with hyperthyroidism, central and/or peripheral autonomic dysfunction (Shy-Drager syndrome, tetraplegia, diabetic or uremic neuropathy, etc), chronic renal failure, renal or cardiac transplantation, congestive heart failure, eclampsia, sleep apnea syndrome, malignant hypertension, systemic atherosclerosis and accelerated hypertensive organ damage. However, in those with primary aldosteronism, renovascular hypertension, pheochromocytoma without paroxysmal hypertension, or those with cardiac pacing, a nocturnal blood pressure fall is ordinarily observed. It may be that a fall in cardiac output rather than in peripheral resistance may be mainly responsible for the nocturnal fall in blood pressure. It also seems that a nocturnal heart rate fall is not responsible for it, since the nocturnal blood pressure fall remained unchanged in patients undergoing cardiac pacing and was disturbed in patients with Cushing's syndrome or hyperthyroidism in whom the circadian heart rate rhythm remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095381 TI - Evaluation of blood pressure measuring devices with special reference to ambulatory systems. AB - As ambulatory blood pressure measurement becomes more widely accepted in hypertension research and in the clinical management of high blood pressure, the number of devices available on the market has increased considerably, reflecting the clinical demand. These devices are expensive, both in terms of capital and running costs. As we rely increasingly on data produced by ambulatory systems, it becomes increasingly important that they be shown to be accurate. Initially protocols for the validation of ambulatory devices were designed on an ad hoc basis, so that many studies were inadequately designed and comparison of data between studies was usually impossible. The American National Standard published by the Association for the Advancement of Medical Instrumentation (AAMI) remedied this situation in part, and the recent publication of the British Hypertension Society (BHS) protocol for the validation of ambulatory systems has further advanced the demand for accuracy. The BHS protocol includes most of the AMMI standard recommendations, but in addition there are sections on observer training, in-use assessment and inter-device variability. In addition, performance characteristics, computer facilities and details on such practical matters as cost and maintenance are sought. Finally, the BHS protocol provides a grading system of validation which allows comparisons between devices and studies. PMID- 2095382 TI - The role of behavioral factors in white coat and sustained hypertension. AB - Studies using ambulatory monitoring of blood pressure have indicated that patients with persistently elevated clinic pressures may be subdivided into two groups, those in whom ambulatory pressure is also elevated (persistent hypertension), and those in whom it is normal (white coat hypertension). The role of behavioral factors in contributing to these two types is discussed. Studies of white coat hypertension suggest that it is not characterized by any generalized physiological abnormality, and that target-organ damage is mild and the prognosis relatively benign. It may represent a conditioned response to the physician. Behavioral factors can significantly influence the diurnal profile of blood pressure, as shown by a comparison of ambulatory pressures recorded on working and non-working days, and in women who experience varying levels of occupational and domestic stress. The role of behavioral factors in the development of sustained hypertension (defined as an upward resetting of the diurnal profile), however, is much less clear. A cross-sectional study of normotensive and hypertensive men has shown that men employed in high-strain jobs are more likely to show a sustained elevation of blood pressure. PMID- 2095383 TI - Various approaches to blockade of the renin-angiotensin system: persistent renin response. AB - The first compounds used to block the renin-angiotensin system were polypeptide antagonists of angiotensin II, administered parenterally. Subsequently, orally active angiotensin converting enzyme inhibitors were developed which were generally well tolerated, and were effective in the treatment of hypertension and congestive heart failure. Today they are well established as therapeutic agents. Nevertheless, the search continues for more specific therapeutic agents such as orally active renin inhibitors and angiotensin II antagonists, and accurate biochemical methods must be available to assess their efficacy. All approaches trigger a considerable compensatory rise in renin secretion which tends to counteract the blocking effect of these compounds. Hence all agents, but particularly the renin inhibitors, must have a good bioavailability and a high affinity in order to overcome the effect of the compensatory renin secretory response. As yet, it is too early to predict whether the potentially more specific renin inhibitors or angiotensin II antagonists will replace the present widely used angiotensin converting enzyme inhibitors. PMID- 2095384 TI - Franz Volhard lecture. Increased systemic vascular resistance and primary hypertension: the expanding complexity. AB - Polygenetic predisposition is a key factor in the multifactorial disorders of primary hypertension. It is suggested that endothelial cell abnormalities are the major factors responsible for the increase in total systemic vascular resistance that leads to an elevation in arterial blood pressure. Thus, resetting of the arterial baroreceptors could be a consequence of endothelial-mediated changes in mechano-electrical transduction in the arterial mechanoreceptors. In consequence, inhibition of the vasomotor centers would be diminished and the resulting neurohumoral excitation would constrict the systemic resistance blood vessels. Later, as left ventricular hypertrophy develops, the inhibitory input of the cardiac mechanoreceptors is also reduced. In normal endothelial cells there is a predominant formation and release of vascular smooth muscle relaxing and growth inhibiting factors. However, it is proposed that genetic changes lead to a predominate formation of endothelium-derived contracting factors and mitogens. The former would augment the neurohumoral vasoconstriction. The latter, aided by the increased arterial pressure and the augmented output of norepinephrine, would lead to structural alterations in the arterial vessels, thus reducing the lumen area, amplifying the vasoconstrictor response to contractile agents and limiting vasodilation. In this way the hypertension would be perpetuated. PMID- 2095386 TI - Insulin sensitivity and hypertension. PMID- 2095385 TI - Parathyroid hypertensive factor. AB - A new circulating hypertensive factor, parathyroid hypertensive factor (PHF), has been demonstrated in the plasma of spontaneously hypertensive rats (SHR) but not in that of normotensive rats. PHF produced a delayed increase in blood pressure with a peak response after 45 min (bolus injection) or 60-90 min (continuous infusion). This increase in blood pressure was coupled with an in vitro increase in calcium uptake in the rat tail artery which had a similar time-course. The evidence that calcium is involved in the mechanism of action is supported by the inhibitory effect of calcium antagonists on the vascular action of PHF. Furthermore, PHF increased the intracellular free calcium concentration in cultured smooth muscle cells from the rat tail artery. Parathyroidectomy and parathyroid transplant experiments indicated that PHF originated in the parathyroid gland. Cultured parathyroid glands from SHR but not from normotensive rats produced a factor in the medium with the same biological property and retention time on high performance liquid chromatography as plasma PHF. A novel cell type was described in the parathyroid gland of SHR, but not normotensive rats, and the percentage of these cells was correlated significantly with the plasma PHF level and the blood pressure level. In some hyperparathyroid patients, plasma PHF and hypertension were both present, and both disappeared after surgical removal of the parathyroid gland. In both animal models and human studies, PHF seems to be associated with low or normal levels of plasma renin and the salt-sensitive type of hypertension. PMID- 2095387 TI - Changing hypertension treatment to reduce the overall cardiovascular risk. AB - The increasing tendency to treat hypertension has markedly reduced stroke mortality but has not significantly reduced the mortality from coronary heart disease. Many explanations for this failure have been proposed and the true reason may never be known. Nevertheless, a number of steps can be taken to improve the degrees of therapeutic protection against coronary heart disease including (1) a complete assessment of all alterable risk factors; (2) effective use of multiple non-drug therapies; (3) use of antihypertensive drugs that reduce other cardiovascular risk factors; and (4) a gradual reduction of blood pressure to levels that will preserve perfusion to vital organs. PMID- 2095388 TI - The impact of hypertension and antihypertensive treatment on the course and prognosis of diabetic nephropathy. AB - The primary cause of arterial hypertension and of the increased morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM) is diabetic nephropathy. About 35% of IDDM patients develop persistent albuminuria, an irreversible decline in the glomerular filtration rate and elevated blood pressure, which collectively contribute to the clinical syndrome of diabetic nephropathy. The excess mortality of IDDM patients with nephropathy is 80-100 times greater than that of an age- and sex-matched non-diabetic population. Diabetic nephropathy is the single most important cause of end-stage renal disease in the Western world, accounting for over a quarter of all such cases. Blood pressure elevation is a frequent finding, even in the early stages of diabetic nephropathy. Elevated blood pressure accelerates diabetic nephropathy, while an effective blood pressure reduction delays the progression of nephropathy and reduces albuminuria. A reduction in glomerular capillary hydraulic pressure may be the crucial factor. All previous reports dealing with the natural history of diabetic nephropathy have demonstrated a cumulative death rate of between 50% and 77% 10 years after the onset of nephropathy. Effective antihypertensive treatment has reduced this rate to 15-20%. PMID- 2095389 TI - Single-channel analysis of the electrical response of bovine aortic endothelial cells to bradykinin stimulation: contribution of a Ca2(+)-dependent K+ channel. AB - The contribution of Ca2(+)-dependent K+ [K(Ca2+)] channels to the electrical response of cultured bovine aortic endothelial cells following bradykinin stimulation was investigated using the patch-clamp method in the cell-attached configuration. Results indicate (1) that bradykinin activates a voltage insensitive K(Ca2+) channel of 40 pS in 150 mmol/l KCl through a second messenger mechanism; (2) that the time-course of the K(Ca2+) channel activation process corresponds to the time-dependent changes in cytosolic Ca2+ triggered by bradykinin; and (3) that there is a direct correlation between the cellular hyperpolarization induced by bradykinin and the activation of the K(Ca2+) channels. It is proposed that the hyperpolarization of bovine aortic endothelial cells following bradykinin stimulation is a result of the activation of K(Ca2+) channels, and not of a modification in the gating behaviour of an inward rectifying K+ channel (lk1) that is also observed in these cells. A more negative membrane potential may, in turn, enhance the Ca2+ influx involved in the bradykinin-induced Ca2+ signalling process. PMID- 2095390 TI - Functional disturbance of the cell membrane in hypertension. AB - Hypertension is associated with a variety of disturbances of cell membrane function. These associations have been attributed to changes in vascular smooth muscle sodium, calcium or PH, although direct evidence is conflicting in this context. While observations have been confounded by poor matching of the populations and technical shortcomings, it seems likely that genuine associations do exist. It is suggested that their significance can only be established by identifying the tissue abnormality responsible for elevated blood pressure. Evidence is cited that this abnormality is a structural increase in the resistance wall: lumen ratio, secondary to increased autonomic activity. A cell membrane disturbance could therefore give rise to hypertension, either through increased trophic responsiveness of the resistance vasculature or increased sympathetic drive to the resistance vessels. There is more direct evidence for the latter than the former. PMID- 2095391 TI - Structure and function of small arteries in hypertension. AB - Both direct in vitro evidence and histological evidence strongly suggest that in essential hypertensive patients there is an alteration in the structure of proximal resistance vessels (small arteries); the media: lumen ratio is increased and the lumen volume is decreased. Although it may be supposed that essential hypertension is related to an increased sensitivity in the resistance vasculature, there is little evidence for this view, either from haemodynamic investigations, or from in vitro experiments. What evidence there is appears to be based primarily on results from the spontaneously hypertensive rat (SHR), but even here small artery sensitivity does not seem to be related to blood pressure. However, two functional abnormalities of the small arteries may be associated with hypertension. First, in small arteries from both essential hypertensive patients and SHR, cocaine has a greater ability to increase the noradrenaline sensitivity than in normotensive subjects, possibly due to increased innervation. Second, genetic experiments with SHR show that the oscillatory activity of small arteries (rhythmic changes in tone in response to agonist activation) is correlated with blood pressure. The role of these structural and functional abnormalities in the pathogenesis of hypertension is not clear. In particular, although the structural changes could account for the increased peripheral resistance, evidence that they are a primary cause of hypertension is lacking. However, the structural changes could play an important role in the morbid consequences of hypertension. Failure to normalize vascular structure with antihypertensive treatment could be one reason why treatment does not improve the prognosis as much as expected. PMID- 2095392 TI - Epidemiology of cardiovascular disease in developing countries. AB - As infection and malnutrition are steadily overcome in the developing world, cardiovascular disease loom large in the profile of morbidity and mortality in these societies. Hypertension, rheumatic heart disease and the cardiomyopathies are already taking their toll and atherosclerosis is certain to pose public health problems soon unless steps are taken now, through attention to known risk factors, to pre-empt or at least minimize its consequences. There are populations in developing countries among whom blood pressure does not appear to rise with age and in whom the prevalence of hypertension is very low. Studies of these communities and of migrant groups indicate that salt has an important effect on blood pressure. In spite of these observations, however, it is well known that black communities tend, on the whole, to show a higher prevalence of hypertension and more severe target-organ damage than white communities. Other distinguishing features are lower cholesterol, triglyceride and low-density lipoprotein fractions and a delayed response to a sodium load in black populations. Economic constraints limit the effective application of stepped-care therapy in the management of moderate to severe hypertension. Beta-blockers and angiotensin converting enzyme (ACE) inhibitors are not so effective in black communities unless combined with diuretics. PMID- 2095393 TI - Irvine Page lecture. Legacies of Irvine H. Page. AB - Irvine Page has played a singularly important part in the field of hypertension for almost 60 years. His first contributions were published in the early 1930s and his most recent, Hypertension Mechanisms, in 1987. The present review outlines some of his accomplishments. It focuses on five areas where his pre eminence is a matter of record, the renin-angiotensin system, serotonin, the mosaic theory, treatment of hypertension and public and professional advocacy of the recognition of this condition and its effects in daily life. PMID- 2095394 TI - Transgenic animals: new approaches to hypertension research. AB - We have shown that it is possible to generate transgenic rats efficiently, allowing direct experimentation in this species, without first testing constructs in the mouse. Having developed the technology for producing transgenic rats, we now hope to generate new and precise models of hypertension and to test candidate genes that may be responsible for the phenotype in existing animal models. The potential to choose between the rat and the mouse for these studies will allow much greater flexibility in experimental design. Many molecular questions are more appropriately addressed in the mouse but questions concerning physiology and development of the cardiovascular system are more appropriately addressed in the rat. With a large number of genes relevant to cardiovascular research now available, transgenic technology will become increasingly important in the future, and even more so if homologous recombination becomes feasible in the rat. The transgenic rat therefore heralds an exciting new dimension in hypertension research. PMID- 2095395 TI - Multigenic human hypertension: evidence for subtypes and hope for haplotypes. AB - Hypertension that occurs before the age of 60 years is strongly aggregated in families, mostly due to genetic factors with weaker contributions from a shared family environment. Hypertension is probably a heterogeneous collection of overlapping subsets of pathophysiological mechanisms, such as dyslipidemia, obesity, hyperinsulinemia and cation metabolism. Highly heritable traits such as sodium-lithium countertransport, urinary kallikrein excretion and a body fat pattern index show evidence of major gene segregation in families with hypertension. They are thought to be intermediate phenotypes in the chain of pathophysiological events leading from specific genes to the distant phenotype of hypertension. They provide evidence of measurable contributions from single gene traits to the susceptibility to hypertension. Genetic linkage studies have suggested that other specific loci (e.g. histocompatibility leukocyte antigen, blood group MN and the haptoglobin protein) contribute to the susceptibility to hypertension. DNA sequencing has shown a point mutation for lipoprotein lipase that conveys susceptibility to lipid abnormalities, and possibly also hypertension, as seen in families with dyslipidemic hypertension. Further application of these approaches, especially in families that include multiple siblings with hypertension, shows promise of a true understanding of how the combined effects of a few specific genes, the polygenic background and selected environmental factors can lead to essential hypertension. This understanding should foster better tailored and more effective approaches to the prevention, diagnosis and treatment of hypertension. PMID- 2095396 TI - Heat stress genes in hypertension. AB - Genetically hypertensive animals such as spontaneously hypertensive rats (SHR) and mice are more sensitive to thermal stress than normotensive controls. Genetic breeding experiments have demonstrated that the gene responsible for thermosensitivity segregates with an increase in blood pressure in the F2 generation and represents a genetic locus of hypertension. Due to a higher transcription rate of the heat shock protein 70 (hsp70) gene, which is a major heat stress gene, the accumulation of hsp messenger (m)RNA is increased in hypertension. Higher thermosensitivity and increased hsp mRNA accumulation are also observed in neonatal cardiomyocytes and cultured vascular smooth muscle cells from SHR, suggesting that these abnormalities are primary in character. This higher hsp70 transcription rate in hypertension could be due to an abnormality in the promoter region, to an interaction between heat stress trans acting factor and heat stress element within the promoter of hsp70 or to an abnormal activation of heat stress trans-acting factor. A study using recombinant inbred animals has indicated that RT1 complex gene(s), a major histocompatibility complex in the rat, may be involved in the development of hypertension. These findings, together with the fact that hsp70 is located in the major histocompatibility complex, suggest that hsp70 gene or associated genes within the RT1 complex are responsible for environmental control of the expression of hypertension. PMID- 2095398 TI - Duration of absorption-enhancing effect of sodium octanoate, sodium hexanoate or glyceryl-1-monooctanoate on rectal absorption of gentamicin in rabbits. AB - The duration of the absorption-enhancing effect of sodium octanoate (C8), sodium hexanoate (C6) and glyceryl-l-monooctanoate (MO) on the rectal absorption of gentamicin (GM) using the hollow-type suppository was investigated in rabbits. To evaluate the duration of the absorption-enhancing effect by pretreatment (treatment of absorption enhancer before GM administration), suppository I containing each absorption enhancer in the cavity was administered into the rectum. Then suppository II containing GM in the cavity was administered at predetermined times (0.33, 2, 6 and 24 h) after the administration of suppository I. Plasma GM levels obtained by the pretreatment with absorption enhancer were compared with those obtained by the simultaneous administration of GM with absorption enhancer. The AUC and Cmax of GM significantly decreased with the pretreatment of C8 (6 and 24 h), C6 (2 and 6 h) or MO (6 and 24 h) before rectal GM administration, as compared with the simultaneous administration of GM with C8, C6 or MO. A marked decrease in the absorption-enhancing effect of C8, C6 and MO on rectal GM absorption was observed by the prolongation of the period between the pretreatment of each absorption enhancer and GM administration. The duration of the absorption-enhancing effect of C6 was shorter than that of C8, whereas this duration of MO was similar to that of C8. The effect of these absorption enhancers disappeared 24 h after the pretreatment. These results suggested that the lowering of the membrane transport barrier function recovered about one day after the administration of C8 or MO. PMID- 2095399 TI - Prevention of gastrointestinal absorption of phenobarbital by activated carbon beads as an oral adsorbent. AB - The in vitro adsorption characteristics of activated carbon beads suitable for oral administration and the original fine powder were examined, using phenobarbital as the test drug. The extent and rate of drug adsorption on carbon in the beads were almost equal to those on the powder. In three healthy volunteers, 10 g of activated carbon beads administered orally 20 min after 120 mg of phenobarbital, reduced the total bioavailability by 57% (p less than 0.005), based on the salivary AUC-value during 96 h and the achieved peak concentration of the drug in salvia by 51%. These results demonstrated the potency of activated carbon beads as a gastrointestinal adsorbent in acute intoxications from phenobarbital. PMID- 2095397 TI - Changing role of the autonomic nervous system in human hypertension. AB - Pathophysiological effects of the autonomic nervous system are clearly seen in young patients with a high cardiac output and borderline hypertension. As the hypertension progresses, there is a change from the hyperkinetic circulation in borderline hypertension to the increased vascular resistance seen in established hypertension. This hemodynamic transition is caused by decreased beta-adrenergic responsiveness and decreased end-diastolic distension of the heart combined with an increased alpha-adrenergic responsiveness of the resistance vessels. In parallel, the sympathetic tone decreases in the course of hypertension. This transition in sympathetic tone can be explained by the hypothesis of the 'blood pressure seeking properties of the brain'. The central nervous system 'seeks' to maintain a higher pressure. When vascular overresponsiveness sets in, less sympathetic drive is needed to maintain a neurogenic hypertension. Sympathetic overactivity in borderline hypertension is associated with overweight subjects, insulin resistance and dyslipidemia. This suggests a new area of research to investigate the basis of metabolic abnormalities in hypertension. PMID- 2095400 TI - Prediction of the pharmacokinetics of cefodizime and cefotetan in humans from pharmacokinetic parameters in animals. AB - Pharmacokinetic behavior of beta-lactam antibiotics (cefodizime and cefotetan) in humans were predicted from the animal data. Total body clearance (CLp) of these drugs in humans (weighting 65-69 kg) were successfully extrapolated from the allometric relationship between the clearance for the unbound drug in plasma and body weight (r = 0.954-1.000) with a power of 0.948-0.991 for cefodizime and 0.700-0.756 for cefotetan. We also predicted the volume of distribution at steady state (Vdss), the volume of distribution in the central compartment (V1) and the volume of distribution at beta-phase (Vd beta) of these drugs in humans from the observed human plasma unbound fraction, inasmuch as the plasma unbound fraction correlated well (r = 0.913-0.995) with the values of Vdss, V1, and Vd beta among various animal species. Based on these predicted pharmacokinetic parameters, we calculated the plasma concentration profiles of these drugs in humans and found a good agreement between the predicted and observed values. We also report here that the prediction is successful when we consider the plasma protein binding of these drugs. PMID- 2095401 TI - Metabolism of diltiazem. III. Oxidative deamination of diltiazem in rat liver microsomes. AB - The main metabolites of diltiazem in rats are acidic metabolites having a carboxyl group which may be formed by oxidative deamination of the dimethylaminoethyl group of diltiazem. In order to identify the enzymes responsible for the deamination and formation of acidic and neutral metabolites [14C]diltiazem was incubated with microsomal and mitochondrial preparations from the liver of SD male rats. Both acidic and neutral metabolites were formed only in the presence of an nicotinamide adenine dinucleotide phosphate generating system. Their formation was remarkable, especially in the microsomes, and inhibited by SKF 252-A, but not by pargyline and iproniazid. The production of neutral metabolites surpassed that of acidic ones. Structural analysis by gas chromatography-mass spectrometry showed that the neutral metabolites are aldehydes which have not been detected in vivo. The results suggest that the dimethylaminoethyl group of diltiazem is oxidized to an aldehyde group by microsomal cytochrome P-450 in the liver. Subsequently, the aldehyde group would be dehydrogenated to the carboxyl group. PMID- 2095402 TI - Pharmacokinetics and enterohepatic circulation of (E)-2-ene valproic acid in the rat. AB - A pharmacologically active monounsaturated metabolite of valproic acid (VPA), (E) 2-ene VPA, was administered by an intravenous bolus dose of 20 mg/kg to normal and bile-exteriorized rats. The total plasma clearance of (E)-2-ene VPA in normal rats was 4.9 ml/min/kg and in bile-exteriorized rats, 7.7 ml/min/kg. (E)-2-ene was recycled in the plasma of normal rats due to enterohepatic circulation. Approximately 32% of the dose was excreted in the urine of normal rats. Of the administered dose to bile exteriorized rats, approximately 27% was excreted in the urine and 38% in the bile. Administration of (E)-2-ene increased bile flow rate, and the induced choleresis lasted for 3-4 h. (E)-2-ene VPA was largely excreted in apparently conjugated form in the urine and bile. The pharmacokinetics of (E)-2-ene VPA were similar to that of the parent drug VPA. PMID- 2095403 TI - Possible role of glutathione depletion in the induction of rate-limiting enzymes involved in heme degradation and polyamine biosynthesis in the liver of rats. AB - Ten compounds with a wide variety of structures, which decreased hepatic glutachione (GSH) content at an early time period after their administration, simultaneously increased hepatic heme oxygenase, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activities in rats. The compounds examined were four alpha, beta-unsaturated carbonyl compounds, two prototype substrates for GSH transferase(s), one epoxide, two isothiocyanates, and an indicator of hepatic function test. Time course studies with 1-chloro-2,4 dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzene (DCNB), which are prototype substrates for GSH transferases, showed that there was an inverse relationship between the early depletion of hepatic GSH content and induction of heme oxygenase, ODC and SAMDC together with a decrease in cytochrome P-450 content and an increase in putrescine content. Buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, also increased heme oxygenase and SAMDC activities, but not ODC, and it tended to enhance the induction of the enzymes evoked by diethyl maleate (DEM), phorone and CDNB with the sustained depletion of GSH content. In contrast, GSH treatment inhibited DEM-, phorone-, and CDNB-mediated induction of these enzymes and the early depletion of GSH content. N-Acetylcysteine failed to inhibit DEM- and phorone-mediated induction of these enzymes and the early depletion of GSH content, while it inhibited somewhat these changes produced by CDNB. The findings suggest that the early depletion of hepatic GSH content is prerequisite for and plays a role in the induction of heme oxygenase, ODC and SAMDC. PMID- 2095404 TI - Metabolism of 3,7-dioxo-5 beta-cholanoic acid in the biliary fistula rodents and rabbits. AB - Intestinal absorption and metabolism of 3,7-dioxo-5 beta-cholanoic acid, were studied in the bile fistula rats, hamsters, guinea-pigs and rabbits. The influence of dose (1 and 100 mg/kg) on the absorption and the metabolism was also estimated. The dioxo bile acid was absorbed efficiently from the intestine and quickly excreted into bile in these animals. Large dose did not retard the absorption rate and showed a significant choleretic effect for a few hours. Species differences were observed in the metabolism of this compound. In hamsters and guinea-pigs, most of the metabolites in the bile were conjugated with either taurine or glycine. The proportion of bile acids amidated with glycine was greater with the large dose. In rats, the biliary metabolites were conjugated with taurine, but not with glycine, whereas in rabbits, glycine conjugates were the only recovered metabolites. Unconjugated metabolites were also detected in the bile of the rodents, and the proportion of them rose to 17-29% after the administration of 100 mg/kg quantities. A small part of unchanged 3,7-dioxo-5 beta-cholanoic acid was excreted into the bile as both the conjugated and unconjugated forms in these animals. The greater part of this compound administered was metabolized to 7-ketolithocholic acid, chenodeoxycholic acid and ursodeoxycholic acid. In hamsters and guinea-pigs, chenodeoxycholic acid was a greater metabolite of this compound than ursodeoxycholic acid, while in rats and rabbits, the amount of ursodeoxycholic acid exceeded that of chenodeoxycholic acid. In rats, the resulting dihydroxy bile acids were further metabolized to alpha- and beta-muricholic acids. PMID- 2095405 TI - Dose-dependent kinetics of methylphenidate enantiomers after oral administration of racemic methylphenidate to rats. AB - The plasma concentration of methylphenidate (MPD) enantiomers after i.v. and oral administration of 0.5-5 mg/kg dose of racemic MPD was compared in rats. In i.v. administration, there was no dose dependence in the pharmacokinetic parameters of both enantiomers in this dose range. In oral administration, although the elimination rate constant of both enantiomers was relatively constant, the total body clearance of both MPD enantiomers decreased remarkably with increasing dose. The relationship between oral dose and the area under the concentration-time curve (AUC) of the individual MPD enantiomers showed a non-linearity. That is, the AUC of both enantiomers increased dramatically with increasing dose more than 2 mg/kg. The recovery (MPD + the metabolite) in urine for 24 h was 16-18% in the range of the oral doses. These results suggest that the dose-dependent characteristics of the MPD enantiomers may be due to the saturation in the presystemic elimination of the drug. PMID- 2095406 TI - Geocancerology: a fundamental and universal discipline. PMID- 2095407 TI - New approaches to ecological oncology. AB - A definition of ecological oncology is given and its subject is discussed. Primary attention is paid to insufficiently studied aspects of this novel scientific discipline: the influence of carcinogens on the natural biocenoses and their role in the evolutional processes, the transformation of carcinogens by living organisms, and the ecological monitoring of environmental carcinogenic substances. PMID- 2095408 TI - The environment and cancer. PMID- 2095409 TI - Radionuclides in the environment. PMID- 2095410 TI - Chernobyl three years later: radiobiologic evaluation of a radioactive contamination. AB - On April 26, 1986, after partial fusion and confining loss by explosion of a nuclear reactor, 5 x 10(7) Ci of radionuclides escaped from Chernobyl. Three years later, maps show contamination by radioactive isotopes (formed during that period) of 21,000 km2 of Soviet soil, mainly in Byelorussia and part of the Ukraine. Decontamination measures have not been effective to date and 135,000 persons are being followed medically, taking into account the radioactive doses they received. An initial excess of morbidity from solid tumors has been noted much sooner than in the case of Hiroshima and Nagasaki, but its significance is in dispute. Three years later, only the extent of the ecologic disaster caused by the radioactive contamination can be confirmed. It is too early to draw conclusions about radiation-induced carcinogenesis for the contaminated population. PMID- 2095411 TI - Atmospheric pollution and heavy metals. PMID- 2095412 TI - Satellite remote sensing of industrial air pollution in the Cracow special protected area. AB - Cracow has been declared a special protected area in the ecological sense. To determine the industrial aerosol content in the air above the Cracow agglomeration, we interpreted satellite images, obtained mainly from the LANDSAT satellite. The ranges, trajectories, and height of smoke plumes visible on the satellite images were investigated in relation to meterological conditions and orography. Satellite images provided convincing evidence of the profound influence of orography on the propagation of industrial pollutants. River valleys create natural air corridors for smoke propagation and are visible especially in the so-called winter satellite images. The results of our direct measurements and interpretation of satellite images indicate that the Katowice and Cracow regions are the most polluted in Europe and that the atmosphere above them contains increasing amounts of aerosol particles. We also found that Cracow is always downwind from emitters. Depending on specific wind direction, emissions from nearby emitters cover either all or part of the urban area. Emissions from farther away may reach Cracow, depending on meterological conditions and orography. Satellite imagery is a very useful tool in monitoring smoke propagation in urban industrial regions. PMID- 2095413 TI - The carcinogenic danger of nitrie pollution of the environment. AB - Presented are the literature data as well as the results of our own investigations on the genotoxic and carcinogenic effects of sodium nitrite (SN). The carcinogenicity of SN detected in animal experiments appears to be related to the formation of nitroso compounds from endogenous nitrosable precursors. Sodium nitrite possesses transforming and promoting effects in cell cultures, as well as mutagenic effects in the bacterial systems, where the predominant effect of SN was compared to that of N-nitrosodimethylamine (NDMA). Prolonged pretreatment with SN amplifies the liver DNA damage in rats in case of NDMA endogenous synthesis. PMID- 2095414 TI - Ultrastructure of gastric epithelium after exposure to mild environmental agents (sodium nitrate, saprol). AB - Environmental chemical agents usually affect the human organism in combination rather than alone. The objective of this study was to determine the effect on the gastric mucosa of the herbicide Saprol alone or in combination with the nitroso compound sodium nitrate. We examined the cells of the gastric endocrine system by electronmicroscopy, and recorded the ultrastructural nuclear and cytoplasmic changes. The herbicide Saprol did not significantly change the ultrastructure of the gastric epithelial cells. Marked changes were noted in nuclei, mitochondria, and secretory granules of the gastric endocrine cells after exposure to both Saprol and sodium nitrate. These changes were significantly more severe after the combined exposure than after sodium nitrate exposure alone. The most affected were the vasointestinal polypeptide-producing D1 cells. PMID- 2095415 TI - Cancer, alcohol, and tobacco. PMID- 2095416 TI - Prevention of smoking in youth. AB - Factors likely to explain the considerable increase in tobacco dependency among young people were identified. They are reviewed together with the motivations, usually unconscious, that cause human beings to smoke. Diverse experiments that have been carried out and that serve as the basis for a multidimensional preventive program are reported. Administration of this program in several secondary schools yielded positive results that have not been recorded previously. PMID- 2095417 TI - Pathogenesis of respiratory carcinogenesis. PMID- 2095418 TI - Protecting workers from noise. PMID- 2095419 TI - Balkan endemic nephropathy and transitional cell carcinoma: two fatal chronic diseases and the environment. PMID- 2095420 TI - Malignant urinary tract tumors occurring endemically in Balkan countries. PMID- 2095421 TI - Lymphoma in AIDS. AB - The lymphoma occurring in AIDS patients is characterized by the following features. 1. It is a B-cell malignant neoplasm of high-grade malignancy resulting from a profound T-cell suppression caused by the cytotoxic effect of a retrovirus that has lymphotropism for the T4 subset. 2. The age of lymphoma patients parallels that of AIDS patients. 3. Prodromal manifestations frequently herald the emergence of the lymphoma. 4. Extranodal involvement is frequently seen. 5. The lymphomas are resistant to treatment, with low patient survival. PMID- 2095422 TI - Practical occupational medicine: astronaut selection; a diver's perspective from 300 m below sea level to 300 km above. AB - In 1989, public selection of a team of four astronauts for the Anglo-Soviet Juno space mission took place. In this article, the author, a Navy Medical Officer, relates his experiences of taking part and discusses the rationale behind the exhaustive protocol of medical investigations involved. PMID- 2095423 TI - Expedition 'Idraren Draren'. AB - In May 1990 a team of 12 personnel from the Royal Naval Medical Service flew to Marrakech and were then transported by truck to the village of Imlil to commence a 12-day trek into the High Atlas Mountains with the primary aim of ascending the summit of Mount Toubkal and encircling the Toubkal Massif. It was then the intention to get off the tourist tracks and to experience life among the Berber tribes, and to trek part of the high Atlas range. PMID- 2095424 TI - The Cambridge Audit System in a service hospital. AB - The introduction of clinical audit into the environment of service hospitals poses particular problems. Experience at RNH Plymouth has shown that one approach, the adaptation of the 'Cambridge Audit System', has succeeded in overcoming certain administrative hurdles and has confirmed the advantages that can accrue from introducing a clinical audit based around a computer system. PMID- 2095425 TI - W(h)ither the naval hospitals? PMID- 2095426 TI - The Royal Naval Medical Stores for Service Afloat: a prospective quantitative study. AB - The contents of the scale of Medical Stores for Service Afloat must provide adequate quantities of drugs to allow proper patient care in a variety of situations often remote from specialist support. The overall make up of the scale is difficult to envisage outside the context for which it was conceived. This study was designed to assess the accuracy of the make up of the scale in three RN ships over a six-month period during a detached deployment. During this time the usage of all consumable items was specifically recorded and the outcome subjected to rigorous analysis in relation to the present scale. The results of the study indicate that in the case of both HMS Ark Royal (AR) and the two smaller ships HMS Edinburgh and HMS Sirius (ES) the quantities of drugs in the majority of cases are in excess of requirements. Of the 290 (AR) and 266 (ES) individual drugs 68% and 40% respectively could safely be reduced by varying amounts, whereas only 7.6% and 4.9% respectively needed to be increased. Furthermore, when these changes are costed the savings that result are 7806 pounds for the AR scale and 1532 pounds for the ES scale. Extrapolation of these figures across the surface fleet produces an overall saving on the costs of drugs of over 87,000 pounds. PMID- 2095427 TI - First World War naval medical officers' journals. PMID- 2095428 TI - Heat illness. PMID- 2095429 TI - Does exposure to CS gas potentiate the severity of influenza? PMID- 2095430 TI - General anesthesia for operations at sea. PMID- 2095431 TI - Calcium exchange in rabbit myocardium during and after hypoxia: role of sodium calcium exchange. AB - Calcium uptake was measured using 47Ca2+ in the isolated and arterially perfused interventricular septum of the rabbit. Experiments were undertaken to determine whether calcium uptake on reoxygenation is linked to recovery of mechanical function and whether calcium uptake is through the sodium-calcium exchange mechanism. During substrate-free hypoxia for 45 min total tissue calcium remained unchanged but immediately upon reoxygenation there was a substantial net gain of calcium. Recovery of mechanical function upon reoxygenation was inversely related to the increase in tissue calcium. Activation of sodium-calcium exchange by perfusion with a low-sodium, zero-potassium, sucrose solution also increased tissue calcium and the relation to mechanical recovery was similar to that observed on reoxygenation. The sodium-calcium exchange mechanism was not affected by hypoxia and could be demonstrated during perfusion with a substrate-free hypoxic solution. Lithium (100 mM) substitution for sucrose prevented the calcium influx induced by a low-sodium and zero-potassium perfusate under normoxic conditions. Lithium substitution early during hypoxia or on reoxygenation did not affect the increase in myocardial calcium on reoxygenation. Amiloride (10(-4)M), presumed to inhibit sodium-hydrogen exchange during hypoxia, had no effect upon reoxygenation induced calcium uptake. It is concluded that the increase in calcium uptake that occurs on reoxygenation after a period of substrate-free hypoxia is related to mechanical recovery. Sodium-calcium exchange may contribute to calcium uptake on reoxygenation in this experimental model but is not the major mechanism. PMID- 2095432 TI - Ischemic nucleotide breakdown increases during cardiac development due to drop in adenosine anabolism/catabolism ratio. AB - Our earlier work on reperfusion showed that adult rat hearts released almost twice as much purine nucleosides and oxypurines as newborn hearts did [Am J Physiol 254 (1988) H1091]. A change in the ratio anabolism/catabolism of adenosine could be responsible for this effect. We therefore measured the activity of adenosine kinase, adenosine deaminase, nucleoside phosphorylase and xanthine oxidoreductase in homogenates of hearts and myocytes from neonatal and adult rats. In hearts the activity of adenosine deaminase and nucleoside phosphorylase (10-20 U/g protein) changed relatively little. However, adenosine kinase activity decreased from 1.3 to 0.6 U/g (P less than 0.025), and xanthine oxidoreductase activity increased from 0.02 to 0.85 U/g (P less than 0.005). Thus the ratio in activity of these rate-limiting enzymes for anabolism and catabolism dropped from 68 to 0.68 during cardiac development. In contrast, the ratio in myocytes remained unchanged (about 23). The large difference in adenosine anabolism/catabolism ratio, observed in heart homogenates, could explain why ATP breakdown due to hypoxia is lower in neonatal than in adult heart. Because this change is absent in myocytes, we speculate that mainly endothelial activities of adenosine kinase and xanthine oxidoreductase are responsible for this shift in purine metabolism during development. PMID- 2095433 TI - A new method of attachment of isolated mammalian ventricular myocytes for tension recording: length dependence of passive and active tension. AB - The study of the Frank-Starling's law in mammalian single cells has been hindered by a lack of an easily performed method of stretching cells. Some authors have succeeded in this but their methods required a great deal of technical expertise and in most cases they have not had much success. We have developed an easy method of stretching mammalian ventricular cells from slack sarcomere length (S.L.) (Lo, 1.77 +/- 0.05 microns) to about 117% of this length. Thin carbon fibers (12 microns in diameter) which can be bound electrochemically to the cell membrane surface have been used. A flexible long fiber of known compliance (80 microns/microN) was attached to one end of the cell and a stiff double fiber (4 microns/microN) to the other end. The cell attachment was relatively easy to perform and successful results were obtained in 80% of the attempts. The displacement of the flexible fiber allows the quantitative measurements of the resting tension in a group of non-stimulated cells and of auxotonic contractions developed upon stimulation in another group of cells. Increasing S.L. from Lo to 105-106% of Lo, an increase in active tension from 0.21 +/- 0.03 mN/mm to 0.26 +/ 0.01 mN/mm (n = 4) could be noticed with a stimulation frequency of 0.5 Hz. An increase in active tension was also observed at 1 Hz. Staircase kinetics were accelerated with stretching; this confirms at the single cell level the hypothesis of an effect of length-dependent activation on the staircase. Eulerian differential stiffness constant was calculated and found to be 13.5 +/- 1.2, a value which is comparable to that described in intact heart. Thus the important stiffness found in the whole heart may be due to intracellular component(s) such as myofilament and/or connectin. PMID- 2095434 TI - Behaviour of energy metabolites and effect of allopurinol in the "stunned" isovolumic rat heart. AB - The pathogenesis of post-ischaemic depression of contractility in myocardium was examined in isovolumic rat heart. 31P-NMR was used to monitor changes in ATP, creatine phosphate (CrP), inorganic phosphate (Pi), and [H+] during brief periods of ischaemia and reperfusion with and without allopurinol treatment. During 5, 10, or 15 min of total global ischaemia, the decline in function (rate-pressure product) correlated inversely with [Pi] (r = 0.92, P less than 0.01). Cardiac function exhibited a slow progressive recovery during 20 min of reperfusion, ultimately reaching only 85%, 78%, and 69% of its pre-ischaemic value following 5, 10, and 15 min of global ischaemia respectively. Following each ischaemic period [ATP], [CrP], [Pi], and [H+] all recovered to control levels within 5-10 min of initiating reperfusion. Allopurinol (2 mM) treatment of hearts made ischaemic for 15 min significantly improved contractile recovery to 89 +/- 7%. Allopurinol also exhibited significant anti-arrhythmic activity during the reperfusion period, decreasing the incidence of premature contractions and the duration of tachy-arrhythmias. Allopurinol had no effect on the final repletion of [ATP] and [CrP], or the recovery of [Pi] and [H+], although the rate of ATP repletion was elevated in the initial 5 min of reperfusion. These results show that neither depletion of the cytosolic high-energy phosphate pool, nor sustained elevations in [Pi] or [H+] are important in the production of post-ischaemic contractile impairment. The beneficial action of allopurinol suggests that xanthine oxidase derived oxygen free-radicals may be involved in the sustained contractile dysfunction following brief ischaemic episodes. PMID- 2095435 TI - Slowly exchanging calcium binding sites unique to cardiac/slow muscle troponin C. AB - Evidence is presented for the existence of slowly exchanging Ca2(+)-binding sites in troponin C (CTNC) of cardiac and slow twitch skeletal muscles. These sites were revealed in the course of experiments aimed at measuring the Ca2(+)-binding properties of TNC in the myofilament lattice. 45Ca bound to chemically skinned muscle fibers or myofibrils of cardiac and soleus muscles was eluted by EGTA in a two-exponential timecourse with a slow phase of a rate constant of about 2 x 10( 4)/s. The slow phase was not found in skinned fiber or myofibrils of psoas, a fast skeletal muscle. However, skinned psoas fibers in which the native TNC was replaced by CTNC exhibited the slow 45Ca elution characteristic of soleus and cardiac preparations, indicating that the slowly-exchanging sites are located in CTNC. These sites are tentatively identified as the Ca2(+)-Mg2+ sites of CTNC on the basis that the slow phase was observed under conditions known to restrict Ca2+ binding to the Ca2(+)-Mg2+ sites. PMID- 2095436 TI - Oxygen uptake by isolated perfused fish hearts with differing myoglobin concentrations under hypoxic conditions. AB - Hearts from three species of fish with varying myoglobin content were perfused with stepwise changes in input perfusate PO2 from approximately 160 to 10 mmHg. Flow through the heart, rate of contraction, and afterload were kept constant. This standardized stroke volume and bulk flow of perfusate to the myocytes since these hearts are nourished by the fluid in the ventricular lumen. In some cases NaNO2 was added to the perfusion medium to decrease existing levels of functional myoglobin. Myoglobin-rich hearts were able to extract a constant amount of oxygen until perfusate PO2 had fallen below 80 mmHg. At this point oxygen uptake began to decline. These hearts consumed oxygen until input PO2 was 10 mmHg or less. When normoxic conditions were restored the myoglobin-rich hearts showed complete recovery. Performance was maintained at a constant level over the entire range of input PO2. Myoglobin-poor hearts and nitrite-treated hearts were unable to sustain constant levels of oxygen consumption in the face of a declining perfusate PO2. These hearts were unable to extract oxygen from the medium and failed at perfusate PO2's of 40 mmHg for naturally myoglobin-poor hearts and 30 mmHg for nitrite-treated hearts. Half-maximal oxygen consumptions were attained by myoglobin-rich hearts at lower input PO2's than either myoglobin-poor or nitrite-treated hearts. The impact of myoglobin in intact heart is apparent at relatively high extracellular PO2's (40-80 mmHg) in this model system. PMID- 2095437 TI - Prevention of cumene hydroperoxide induced oxidative stress in cultured neonatal rat myocytes by scavengers and enzyme inhibitors. AB - Oxidative stress induced by cumene hydroperoxide was studied in cultured neonatal rat myocytes. A progressive increase of irreversible cell injury as determined by leakage of the cytoplastic enzyme alpha-hydroxybutyrate dehydrogenase (alpha HBDH) from the cells was noted at concentrations ranging from 25-100 microM cumene hydroperoxide (incubation time 90 min). Cumene hydroperoxide-induced damage was reduced or prevented by several compounds: the application of Trolox C, a water-soluble vitamin E analogue, and of phospholipase A2 inhibitors chlorpromazine and (to a lesser extent) quinacrine prevented alpha-HBDH release. ICRF-159, a chelator of divalent cations, ascorbic acid, a potent antioxidant, and the cysteine protease inhibitor leupeptin did not reduce the cumene hydroperoxide-induced cytotoxicity. Detoxification of hydroperoxides by the glutathione peroxidase system results in an increased flux through the pentose phosphate shunt and loss of NADPH. Glucose inhibited the cumene hydroperoxide induced alpha-HBDH release, probably by replenishing NADPH. These results indicate that cumene hydroperoxide, after exhaustion of the glutathione system, induces irreversible injury in cultured myocytes by a mechanism that depends to a large extent on deterioration of cellular membranes caused by lipid peroxidation and phospholipase activation. PMID- 2095438 TI - Enhanced deposition of predominantly type I collagen in myocardial disease. AB - The myocardium consists of a muscle fibre array surrounded and interspersed by a network of connective tissue, principally collagen, which maintains the functional integrity of the heart. Changes in collagen composition may therefore contribute to altered ventricular function. Collagen composition was examined in cardiac tissue from 15 patients undergoing orthotopic cardiac transplantation. Of these, 10 had severely impaired left ventricular function due to coronary artery disease. The remaining five had dilated cardiomyopathy. Normal heart tissue was taken at autopsy from 25 patients who died of causes unrelated to cardiovascular disease. Left ventricular collagen concentration, estimated from hydroxyproline levels, increased from 48.6 +/- 4.1 mg/g dry weight of tissue in the control group to 95.3 +/- 9.7 mg/g (P less than 0.01) in patients with dilated cardiomyopathy and to 63.5 +/- 9.8 mg/g in the coronary artery disease group. This increase was attributable to an increase in absolute concentrations of both type I and III collagen, determined by separation of cyanogen bromide peptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis. However, there was a significant decrease in the proportion of type III collagen (compared with type I plus III) from 41.8 +/- 1.1% in controls, to 34.6 +/- 1.5% (P less than 0.01) in the coronary artery disease group and 35.8 +/- 2.8% (P less than 0.05) in the dilated cardiomyopathy group. These results suggest that excessive collagen production, with a preponderance of type I, occurs in these forms of myocardial disease, indicative of a remodelling of the collagen matrix, which, by increasing passive myocardial stiffness may contribute to impaired heart function seen in these groups of patients. PMID- 2095439 TI - Influence of phospholipid polyunsatured fatty acid composition on some metabolic disorders induced in rat cardiomyocytes by hypoxia and reoxygenation. AB - The influence of membrane polyunsaturated fatty acid (PUFA) composition on lactate production, energy status, enzyme leakage and cell defences against oxygen free radical production was studied in cultured rat ventricular myocytes during hypoxia and reoxygenation. After 4 days in a conventional serum supplemented medium, the cardiomyocytes were incubated for 24 h in synthetic media containing either linoleate and arachidonate (SM6 Medium) or linolenate and eicosapentaenoate (SM3 Medium) as unique source of PUFA. The fatty acid n-6/n-3 ratio of phospholipid was 13.1 in SM6 cells and 0.9 in SM3 cells. Hypoxia induced an increase in lactate production, severe decreases in ATP and ADP, leakage of cellular lactate dehydrogenase and reduction of superoxide dismutase and glutathione peroxidase activities. Reoxygenation of hypoxic cells reduced lactate production to normal aerobic values and allowed slight resynthesis of ATP from AMP. However, lactate dehydrogenase release was not stopped by reoxygenation, and decreases in superoxide dismutase and glutathione peroxidase activities were not avoided. The majority of the biochemical parameters measured during normoxia, hypoxia and reoxygenation were not significantly affected by changes in the fatty acid composition of membrane phospholipids, except for reduced superoxide dismutase activity which appeared earlier in SM3 cells during hypoxia. We conclude that the sarcolemmal PUFA composition of cultured rat ventricular myocytes does not significantly influence altered cell metabolism elicited by hypoxia and reoxygenation. PMID- 2095440 TI - The relationship between cardiac function and metabolism in acute adriamycin treated perfused rat hearts studied by 31P and 13C NMR spectroscopy. AB - Acute adriamycin cardiotoxicity was studied in the isolated, perfused rat heart by 31P and 13C NMR spectroscopy at flow rates of 15 and 5 ml/min. Treated hearts received a total dose of 13.5 mg of adriamycin. 31P NMR spectra were collected at the beginning and end of each experiment, and cardiac function was recorded throughout. Hearts were perfused with [1-13C]glucose, and 13C NMR spectra were recorded in the presence and absence of the drug. At normal flow (15 ml/min), adriamycin caused a decline in cardiac function which was reversible when the drug was removed. There were no changes in high energy phosphate levels. The labeling of glutamate was unchanged in the presence of adriamycin; however, there was a slight increase in the labeling of lactate and alanine. At reduced flow (5 ml/min), control hearts exhibited a small decrease in ATP and phosphocreatine levels, and cardiac function was depressed. These changes were reversible when normal flow was restored. Nevertheless, adriamycin treatment at low flow caused an irreversible decline in function and in hydrolysis of ATP and phosphocreatine. At reduced flow, the control and drug-treated hearts showed similar labeling of the glutamate pool; however, there was significantly greater labeling of lactate and alanine during adriamycin treatment. These results indicate that adriamycin is more toxic under reduced flow conditions. Impairment of cardiac function by adriamycin without changes in glutamate labeling suggests that this drug alters the relationship between cardiac function and energy production. PMID- 2095441 TI - Mechanisms of cardiovascular drugs as antioxidants. PMID- 2095442 TI - Twelve tips for organizing an Objective Structured Clinical Examination (OSCE). PMID- 2095443 TI - A self-study of clinical evaluation in the McMaster clerkship. AB - The McMaster University Undergraduate MD Program participated with nine other schools in a pilot self-study of clinical evaluation under the auspices of the Association of American Medical Colleges. Clerkship planners and teaching faculty responded to questionnaires provided by the AAMC Clinical Evaluation Program, dealing with evaluation system problems. Top ranked problems, as perceived by the McMaster faculty, are presented and compared with the major problem areas seen by the overall group of the nine other schools. Two of these items deal with: (1) the lack of transmission of evaluative information about clerks from one unit to subsequent ones; and (2) faculty unwillingness to record negative evaluations. The former is seen as a serious problem both at McMaster and at the other schools; the latter only at McMaster. The discussion focuses on attempts to explain why these problems exist at McMaster and offers some suggestions for dealing with them. PMID- 2095444 TI - Assessment of a brief interviewing course using the Helping Relationship Inventory: an interviewing course assessment. AB - A brief second year interviewing course consisting of 9 hours of small group meetings was evaluated by administering the Helping Relationship Inventory (HRI). Other studies have used the HRI to assess longer interviewing courses that included both small groups and large class lectures. The purpose of this study was to use the HRI to see if objective improvement in communication skills could be found in this relatively brief interviewing course. One hundred and nine students, representing an 80% return rate, completed all questions on the HRI pre and post-tests. Analysis of pre- and post-test data showed that students became significantly more understanding (p less than 0.0001) and significantly less 'supportive' or pacifying (p less than 0.0001) by the end of the course. There were no differences found on pre- and post-test HRI scores comparing males (n = 71) and females (n = 38). This study demonstrates that even brief small group interviewing courses can effect a positive change in students' communication skills. PMID- 2095445 TI - The use of patients as student evaluators. AB - Current evaluation of medical students in their clinical clerkships is usually performed by their clinical tutors, and emphasizes knowledge, skills and behavior. However, it is not at all certain that the clinical tutors adequately appreciate the behavioral aspects of the student-patient interrelationship. Since these interactions are not directly observed by the tutors, their evaluation is based largely on second hand information. In the present study, patient opinion regarding student behavior was collected and compared to tutors' evaluation of the student. One hundred and eighty one patients and 31 clinical tutors evaluated 41 medical students during a 6 week internal medicine clerkship, using a specially designed patient questionnaire and tutors' rating form. An analysis of the correlation between tutors' individual rating parameters and the global score revealed high correlation for those parameters associated with clinical knowledge and skills, but lower correlations for parameters associated with students' relationship to patients. The study reveals difficulties associated with the evaluation of students by patients. The process is time-consuming, and introduces tension between students and patients. In addition the patients appeared to be poor discriminators in evaluating medical students. Finally, the study points out that tutors do not assign sufficient importance to the student-patient relationship in the global clerkship score. PMID- 2095446 TI - The influence of the introduction of objective structured practical examinations in physiology on student performance at King Faisal University Medical School. AB - The Department of Physiology at the College of Medicine and Medical Sciences, King Faisal University (KFU) had serious concerns about the effectiveness of the practical classes in motivating student learning and in achieving the objectives of these practicals. A new form of evaluation, the objective structured practical examination (OSPE) was introduced in June 1987. At KFU, the introduction of OSPE has led to a marked improvement in the mean scores for the laboratory component of the final examinations in the physiology courses. Such an improvement was not consistently observed in the other components of the examinations. Performance in stations evaluating skills was in general better than in those testing analytical and interpretive abilities. Female students performed significantly better in OSPE than male students in 4/5 and 3/5 physiology I and II examinations. Such gender differences were not observed in the written examinations. PMID- 2095447 TI - Training residents in clinical teaching skills: a resident-managed program. AB - A resident-managed program to improve teaching skills and examine residents' perceptions of teaching was conducted for internal medicine residents at Maine Medical Center. A modification of the Fewett (1982) teaching model was applied as an adjunct to an ongoing resident teaching program. Twenty-six of 29 residents voluntarily participated in a series of workshops over a 6 month period. A low attrition rate and high level of acceptance of the format were observed. Teaching programs are manageable by a senior resident and can be of potential benefit. PMID- 2095448 TI - Observer evaluation as a tool for field level evaluation of performance. AB - A field-level assessment of the job performance of a category of health professionals was carried out using the technique of non-participant observation of client-health worker interactions. Presenting the data so obtained in the form of a 'performance profile' enabled identification of areas in which this category of health workers showed a lower level of performance, indicating areas where alterations in basic and in-service training programmes are required. PMID- 2095450 TI - The effect of prototype-based versus attribute-based presentation forms on the acquisition of a medical concept. AB - The purpose of this study was to determine the differential effect of two presentation-forms on the acquisition of the concept of shock. It is hypothesized that presenting a prototype facilitates learning and retention of the concept shock compared with verbally enumerating the attributes of the same concept. A group of 106 students from nursing education participated in the experiment. A matched group design guided the assigning of students to different instructional conditions. The instructional program consisted of expository texts, different types of questions and feedback. In the experimental condition eight videotaped typical cases of shock were incorporated in the program. Data-analysis resulted in confirmation of the hypotheses (p less than 0.01), i.e. new instances of shock were identified more frequently by students of the experimental group, while these students were also more able to list commonalities and differences between different cases of shock. This finding supports the prototype-paradigm in concept learning and implies the recommendation to organize lessons in clinical reasoning or diagnostic behavior around typical cases of concepts. PMID- 2095449 TI - To what extent are medical interviewing skills teachable? AB - Growth patterns of medical interviewing skills during a 6-year undergraduate curriculum are assessed by studying 563 medical students taken from five year groups, interviewing simulated patients. In a cross-sectional, quasi-experimental design their skills are rated by means of the Maastricht History-taking and Advice Checklist (MAAS), an observation instrument which measures five categories of interviewing skills pertaining to initial medical consultations. The findings suggest that the skills for 'history-taking', 'presenting solutions' and 'structuring of the interview' are effectively learned. These learning effects result from a continuous small group teaching program with expert and peer review of videotaped encounters with simulated patients. The teaching effects of this program seem less for the skills pertinent to the phase of 'exploring the reasons for encounter' and to the 'basic interviewing skills', because the students' growing medical knowledge and the increasing ability to solve medical problems exert a counteracting influence on the acquisition of these easily deteriorating skills. The results might be helpful to curriculum planners in order to make their programs for medical interviewing skills more effective. PMID- 2095451 TI - More attention should be paid to the formation of attitudes in doctors. AB - The scientific explosion of the second half of this century has led in the medical field to a process of specialization and sub-specialization, with heavy emphasis on knowledge and technical skills and neglect of the traditional humane and interpersonal aspects of the practice of medicine. An important part of clinical competence of the physician is thereby threatened. Therefore faculties should be encouraged to devise ways of teaching the formation of the right attitude as an integral part of the curriculum and include the testing of attitude in their evaluation of final competence of the student. PMID- 2095452 TI - Choosing a career within medicine: do the style and structure of medical schools make a difference? AB - Thirty people close to graduation from each of the medical schools at McMaster University (MU), Rijksuniversiteit Limburg (RL), Tufts University (TU) and the University of Edinburgh (UE) were interviewed about their future career choices. Few of them recognized features of the medical programmes as influences on their choices, except for the research experience available to some students in an Honours year in Edinburgh and during electives in RL. For all groups, having done research at any time was associated with plans to do research in the future. Differences in other aspects of their development as physicians were found to be associated more often with whether the medical school had post-secondary education prerequisities for admission (MU, TU) or not (RL, UE), than with whether the programmes used traditional education methods (TU, UE) or not (MU, RL). PMID- 2095453 TI - Assessment of an interactive microcomputer-videodisc programme for teaching medical students to evaluate the peripheral blood smear. AB - An interactive microcomputer-videodisc programme for providing instruction in interpreting the peripheral blood smear was evaluated by 23 medical students. The mean scores of the students on a test of interpretation of photomicrographs of blood smears increased significantly after use of the teaching programme. The students' responses to a questionnaire indicated that they viewed computer based instruction as a useful learning tool. The results of the study suggest that computer assisted instruction may be one method for addressing some of the current problems in medical education. PMID- 2095454 TI - Decision making in cancer treatment: age and socio-economic status as independent variables. AB - Treatment decision making in cancer patients is dependent on tumour variables, patient variables, and physician bias. Patient age and socio-economic status were examined as independent variables in treatment decision making. Bias towards offering treatment options to younger, more socially active patients was found. PMID- 2095455 TI - Hypnosis training enhances communication skills. AB - We hypothesized that attending a brief, introductory hypnosis training workshop enhances communication skills. We speculated that attending such a programme would enable residents in a Family Medicine training programme to identify the psycho-social concerns of their patients more rapidly. To test the hypothesis five residents were videotaped interviewing a standardized patient before and after attending a hypnosis workshop. A blinded observer reviewed the tapes. The observer counted the number of comments made by the residents on their patient's non-verbal behaviour and the time required to confront the patient's primary concern. The residents made more comments on their patient's non-verbal communication after training than before, and more than the controls. They also shortened the time until they addressed the primary concern. This difference was not statistically significant. There was however a strong negative correlation (r = -0.92) between the number of these comments made and the time required to unveil the patient's hidden agenda. An increased awareness of non-verbal cues, achieved through hypnosis training, appears to help reveal a patient's hidden agenda. The implications of these findings are discussed. PMID- 2095456 TI - A practical approach to housestaff teaching conferences in a multi-site training program. AB - The challenges of providing useful didactic teaching conferences for house officers and students on ward rotations in a program with several training sites are reviewed. An approach used by the Division of General Internal Medicine at the University of Washington minimizes these difficulties and may be of interest to others responsible for the teaching of house officers. PMID- 2095457 TI - How much practice makes perfect? A quantitative measure of the experience needed to achieve procedural competence. AB - Based on the general learning curve formula, the authors have devised a method to estimate the experience needed to achieve competence in the performance of medical and surgical procedures. The method quantitates the learning ability of the trainee, the technical difficulty of the procedure, and the expected level of competence. Two retrospective applications demonstrate the ease of use and reliability of the method. PMID- 2095458 TI - Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis. AB - All nucleated animal cells synthesize heme to provide the prosthetic group of respiratory cytochromes. Large amounts of heme are synthesized by erythroid cells for hemoglobin production and by liver cells for drug-induced cytochromes P450. This review focuses on the first enzyme of the heme biosynthetic pathway, 5 aminolevulinate synthase (ALAS), which catalyzes the rate-controlling step in liver and possibly other tissues. We report that there are two distinct human genes for ALAS: one, a housekeeping gene, is probably ubiquitously expressed while the other is active only in erythroid tissue. By contrast it has been reported that, for porphobilinogen deaminase, the third enzyme of the heme pathway, there is a single human gene with two promoters; one functional in all tissues, the other erythroid specific. In liver, transcription of the housekeeping ALAS gene is induced by drugs and repressed by heme. Heme also acts in a novel way to prevent transport of ALAS into mitochondria, its site of function. Porphyrias result from inherited defects in enzymes of the heme pathway subsequent to ALAS and the molecular abnormality is now known for the most common subtype of acute intermittent porphyria. In developing red cells, levels of ALAS are regulated by increased gene transcription and by a post-transcriptional mechanism, in which iron most probably controls translation of erythroid ALAS mRNA through an iron-responsive element identified in the 5' untranslated region of the mRNA. The human erythroid ALAS gene is located on the X-chromosome, suggesting that a defect in this gene may be responsible for X-linked sideroblastic anemias. PMID- 2095459 TI - Non-radioactive in situ hybridization of DNA probes to chromosomes and nuclei. A comparison of techniques. AB - We have used a moderate repeat probe and a number of single copy DNA probes of varying sizes to compare different approaches to non-radioactive in situ hybridization. We have compared the ease and speed of the methods, the sensitivity, resolution, reproducibility, the availability and costs of reagents, and the potential for clinical application. Following biotinylation or mercuration, the probes were hybridized to human metaphases and nuclei and detected by different affinity systems. Visualization of signals was by brightfield, phase contrast, fluorescence or reflection contrast microscopy. As a result of our study, we recommend two simple and reliable methods using the biotinylation approach with either the avidin-peroxidase conjugate and diaminobenzidine detection and reflection contrast microscopy, or the streptavidin-alkaline phosphatase conjugate and bromochlorodinolyl phosphate nitroblue tetrazolium chloride detection using phase contrast microscopy. PMID- 2095461 TI - Methods of detection of single base substitutions in clinical genetic practice. AB - The ability to diagnose human diseases at the DNA level has become possible because of a rapid development in DNA technology, particularly in the area of detection of single base substitutions. Mutations in the genomic DNA of a particular gene may be inferred indirectly using linkage analysis and restriction fragment length polymorphisms. However, direct detection of the mutation is the more favourable approach. The advent of the polymerase chain reaction to amplify specific regions of genomic DNA or mRNA has enhanced the speed and sensitivity of many of the screening and diagnostic procedures. Screening methods have been developed that will detect at least 70% and, with some methods, close to 100% of all mutations. The methods include ribonuclease A cleavage, denaturing gradient gel electrophoresis, chemical cleavage of mismatch and direct sequencing. Choice of method is based on a number of factors and will depend on the structure of the gene to be analysed. Following identification of a mutation using one of the screening procedures, prenatal diagnosis and carrier testing can be offered. The overall aim is to develop a method that has the potential to determine the mutation present in an index case of a previously untested family in a few days, thus allowing any other relevant family member to be tested. PMID- 2095460 TI - Role of acrocentric cen-pter satellite DNA in Robertsonian translocation and chromosomal non-disjunction. AB - The centromeres and short arms of the human acrocentric chromosomes have in common several families of tandemly repeated DNA. Recent analyses have revealed that, within some of these families, clearly distinct subfamilies have evolved that are unique to one or a subset of the different acrocentric chromosomes. The existence and maintenance of subfamilies common to different chromosomes entail a process of regular exchange between the non-homologous chromosomes. This process is suggested for the evolution of an alpha satellite subfamily recently found on chromosomes 13, 14 and 21. The presence of this alpha subfamily may allow pairing between these chromosomes leading to the observed non-random participation of these chromosomes in t(13q14q) and t(14q21q) Robertsonian translocations. The available data also indicate a very similar molecular organisation of the cen pter region for chromosomes 13 and 21. This latter feature may further allow the two chromosomes to undergo a relatively extensive degree of meiotic pairing (in a manner analogous to that seen in the pseudoautosomal regions of the X and Y chromosomes), thus predisposing these two chromosomes to errors in meiotic segregation and non-disjunction. PMID- 2095462 TI - [HIV infection. The biological mechanism]. PMID- 2095463 TI - [Preparation for ceramometal crowns]. PMID- 2095464 TI - [Bite-wing and early diagnosis of interproximal caries]. PMID- 2095465 TI - [The accuracy of ophthalmological measurements]. AB - Main principals of metrology of measurement being conducted in research studies and in practice of ophthalmologists are stated. Characteristics of casual and systematic errors are described and their causes explained. Concrete measures for increasing the accuracy of ophthalmologic measurements are proposed: coordination of works in research institutes and chairs of ophthalmological profile and metrologic organizations of the state standard on metrologic provision; publication of papers devoted to the methods of treatment of measurement results; introduction of foundations of metrology into the program of education for refreshment courses of physicians-ophthalmologists. PMID- 2095466 TI - [A method and a device for the differential diagnosis of retinal pathological states]. AB - A new method and a device--a stimulator ophthalmological KNSO 1-88 "Phosphene" is suggested for differential diagnosis of pathologic conditions of the retina. It is shown that by means of the proposed method, after 20-25 minutes of dark adaptation the threshold of electric sensitivity by phosphene increases differently with respect to the initial level (on the first minute of dark adaptation): in norm--by 15.2%, in optic nerve atrophy--by 14%, in pigmentary and nonpigmentary forms of retinal dystrophy--by 33.2%. Thus, investigation of the threshold of electric sensitivity by phosphene presents valuable supplementary data for differential diagnosis between optic nerve atrophy and nonpigmentary form of retinal degeneration: in optic nerve atrophy the degree of the threshold increase of absolute electric sensitivity differs, as a rule, but a little from normal values, while in pigmentary and nonpigmentary forms of retinal degeneration it is 2-3 time above norm. PMID- 2095467 TI - [The diagnostic importance of the macular color test in vascular optic neuropathies]. AB - A color-macular test is proposed for diagnosing functional changes in the optic nerve in acute vascular optic neuropathies. The diagnostic value of the test was proved in investigation of sick and clinically healthy fellow eyes of 80 patients with acute vascular optic neuropathies associated with atherosclerosis, aged from 30 to 74 years, as compared with a control group (60 persons of the same age and with the same general vascular pathology). PMID- 2095468 TI - [The study of color vision in children]. AB - The paper analyses results after investigation of color perception in 520 children (264 boys and 256 girls), aged 3-5 years, by means of two simple tests: a "Pfluger-Trident Test" (Velhagen) and a "Simplified Test of Color Vision" (Fletcher). It is proved that in children of under school age color perception is already developed enough and can be investigated for detecting disturbances in color vision. PMID- 2095469 TI - [A device for the objective study of accommodation]. AB - The paper describes a method and a device allowing to objectively determine the volume and stability of accommodation. The device is a refractometer having a stimulator of accommodation. The stimulation of accommodation can be realized by changing the distance in the eye system--the test-object, as well as by introducing positive and negative spherical lenses into this system. It is shown that this method is effective for selection of correction for near in patients with asthenopic complaints and a small volume of accommodation. PMID- 2095470 TI - [The complex study of the iris in transformed light]. AB - Complex investigations of the iris in a transformed light by methods of iridochromoscopy, iridochromophotography, examination in a polarized light, transillumination in red light and fluorescence angiography was conducted in 25 eyes of patients with open-angle glaucoma, 10 eyes of patients with anterior flaccid uveitis and in 23 healthy eyes (a control group). It was found that in patients with open-angle glaucoma and anterior flaccid uveitis trophic and vascular changes in the iris predominated, as compared with control. The most typical for open-angle glaucoma changes in the iris were atrophy of the stroma with predominant involvement of the pupillary zone, exogenic pigmentation of the pupillary and ciliary zones, destruction of the pigment margin of the pupil, thickening of the anterior border layer, pseudoexfoliation of the pupillary margin, defects in the posterior pigment layer, being more extensive in the pupillary zone, as well as disturbances in permeability of the iris in a combination with hypoperfusion and rare bundles of microneovascularization in the area of a lesser arterial circle and the ciliary zone. In case of flaccid uveitis, the most frequent changes were diffuse atrophy of the iris, efflorescence of the pupillary margin, destruction of the pigment rim of the pupil, multiple defects in the posterior pigment layer along its whole length, increased permeability of vessel, microneovascularization of the iris stroma in a form of a thin vascular network. PMID- 2095471 TI - [The rhythmic ERG in the diagnosis of diabetic retinopathy in cataract patients]. AB - The paper describes a new method for diagnosing initial stages of diabetic retinopathy in the presence of cataract--analysis of amplitude parameters of averaged ERG. The usage of different frequency stimuli allows to separately judge about the state of peripheral (10 Hz) and central (40 Hz) segments of the retina. The stage of diabetic retinopathy can be judged by degree of depression of rhythmical ERG. Ophthalmoscopic and fluorescein angiographic verification of the method conducted in 70 patients (94 eyes) after cataract extraction confirmed its high informativeness. PMID- 2095472 TI - [A new method for analyzing fluorescein angiograms by using a computer technic]. AB - A new method is proposed for interpretation of fluorescence angiograms by means of computers. The system of analysis of images on the basis of a computer SM-1420 and original program provision was used. Certain methods of fluorogram analysis are discussed. The analysis of curves of fluorescence dilution allowed to detect and quantitatively determine disturbances in arterial blood circulation in pathology of venous circulation. A modified method of profile densitograms is proposed for quantitative determination of changes in the foveal vascular zone. Element-by-element treatment used for quantitative transfiguration of images allowed to reveal the concerned details of the eye fundus images. PMID- 2095473 TI - [A new ultrasonic method for studying the status of the blood supply to the optic nerve]. AB - For investigation of the state of optic nerve blood supply a duplex ultrasound scanning was used. It is known that such equipment begins to gain popularity in general diagnostics. A special method for investigation of the state of optic nerve blood supply (both of the disc and its orbital part) was worked out and allowed to receive 7 hemodynamic parameters characterizing the state of hemodynamics in norm and in optic nerve atrophy or its suspicion. Thus, a pulsatile index being 1.57 +/- 0.21 in norm, increased to 2.11 +/- 0.13 in atrophy. Systolic-diastolic ratio in norm 5.01 +/- 0.21 increased to 7.25 +/- 0.13 in atrophy. The peak systolic rate of blood supply in norm 32.7 +/- 1.8 cm/c decreased to moderate indices 16.9 +/- 1.3 cm/c. Maximum and moderate rates were also decreased twice as compared with norm. Volume rate of blood flow being 5.02 ml/min. in norm, decreased to 2.05 +/- ml/min. in atrophy. The data obtained are statistically authentic. Thus, duplex equipment can be used for investigation of the state of hemodynamics in short posterior ciliary arteries that nourish the optic nerve. PMID- 2095474 TI - [Aberrometry in the diagnosis of eye diseases]. AB - Four methods (by means of Smirnova-Korniushina's aberrometer; with the help of aberroscope--Cherning's lattice; by presenting a figure of a cross; and by automatic refractometry through different portions of the pupil) were used for studying aberration of the optic system of the eye in 490 persons. Among them, 37 were healthy persons, 27--patients with ametropia of moderate degree, 24--with high myopia, 9--with astigmatism above 3.0 D, 16--with monocular diplopia, 327- with keratoconus, 7--with scars of the cornea, 21--with initial cataract, 47- after keratotomy. In norm and in ametropia to 6.0 D, a histogram of refraction distribution by the pupil has a small disperse and a pronounced peak, the Cherning's lattice is straight. In high myopia, the disperse of refraction increases, the peak is slightly pronounced, the lattice is curved along the margins. In astigmatism, the disperse of refraction is great, but there can be peaks. The whole lattice is curved. In monocular diplopia, two more peaks can be seen on the histogram. The lattice is greatly curved. In keratoconus, aberrometry without correction is possible only at the initial stage and shows a rather mixed picture. The histogram of refraction represents a low irregular row. In aberroscopy, the bands are greatly curved, frequently overstep the bounds of the frame that itself looses a form of a circle, becomes oval or polygonal. Contact correction improves the aberration picture considerably. In scars of the cornea, the lattice is distorted and infrequently repeats their forms. In initial cataract, the course of the bands becomes interrupted and rounded spots appear between them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095475 TI - [The current status and prospects for using the method of photoelasticity in ophthalmology]. AB - The paper analyses results after a study of a complex of questions connected with the method of photoresiliency in ophthalmology. The notion about the nature of a strained-deformed state of the cornea, regularities in formation of a photoresilient picture are discussed on the grounds of experiments on eye biomechanics, a study of optic transformation of polarized light, calculations and mathematic simulation. The paper describes a calculation-experimental method for measuring the tensions acting in the cornea, deciphering of isochrome and isocuneiform fields, data on the usage of computers for automatic treatment and analysis of images. On a great group of clinical observations the practical value of the method is shown and perspectives of its further study conformably to the tasks of research studies and practical ophthalmology are determined. PMID- 2095476 TI - [A new method for the diagnosis of uveitis of Neisseria etiology]. PMID- 2095477 TI - [The photosensitization of uveal melanoma cells by ionizing radiation]. AB - A study of the character of changes in melanoma cells "in vitro" subjected to successive beta-radiation and light energy of low intensity has revealed a more expressed loss of cells as compared with a "pure" ionizing action. Essential differences in the cells density in the monolayer appear already by the 3d-8th day and reach the maximum 2-3 weeks later. The dynamics of changes in the cells density isn't connected with the cellular type of the tumor and initial density isn't connected with the cellular type of the tumor and initial density of their distribution in the monolayer. The duration of the culture existence becomes shorter. If monolayers not subjected to the action perished after 54.0 +/- 6.2 days, after beta-radiation 35.2 +/- 2.4 days later, then after combined action they perished 17.2 +/- 2.6 days later. Thus, the effect was revealed that is actually opposite to a recently discovered phenomenon of photoreactivation of ionizing injury. Despite difficulty of interpreting possible mechanisms of the discovered phenomenon, it is already possible to suggest about its possibility to be used in treatment of pigmentary new formations. PMID- 2095478 TI - [The use of magnetic fields in ophthalmology]. PMID- 2095479 TI - [The results of the discussion on the indications for radial keratotomy in low, moderate and high myopias]. PMID- 2095480 TI - [Increased efficiency in detecting and treating initial myopia in children]. PMID- 2095481 TI - [The choice and dosage of antibiotics in bacterial ulcers of the cornea]. PMID- 2095482 TI - [The distribution of insulin-containing cells in the developing tissues of the common frog (Rana temporaria)]. AB - Monoclonal antibodies to pig insulin were used to follow the changes in localization of insulin-containing cells during the ontogenesis of the brown frog, Rana temporaria L., from stage 20 (Dabagian, Sleptsova, 1975) until completion of metamorphosis and beginning of active nutrition. Insulin-containing were localized in brain, surface epithelium, intestine, olfactory epithelium, taste teats, kidney tubules, ciliated epithelium of the oral cavity, pancreas, Jacobson and interjaw glands was found out. Localization of insulin-containing cells and type of their specific fluorescence varied at different stages of development. Formation of the insulin-containing system of amphibians on the whole is typical for the development of diffuse endocrine system in vertebrates. PMID- 2095483 TI - [The differentiation of prolactin cells in an organ culture of chick embryo adenohypophysis]. AB - We have studied differentiation of prolactin cells in explants of cephalic and caudal parts of Rathke's pouch of 4.5 day and 5.5 day old chick embryos after their incubation in vitro lasting for 7-8 days. Indirect immunofluorescence using an antiserum against bovine prolactin was used to detect prolactin cells in the cultures. Differentiation of prolactin cells was detected regularly in explants of the cephalic lobe of the adenohypophysis anlage in 5.5 day old embryos; under certain growth conditions prolactin cells were found in explants of the same lobe in 4.5 day old embryos. Prolactin cells were either absent or found in small numbers in cultures of the caudal part of adenohypophysis of 5.5 day old embryos. Our results provide evidence for the appearance of the committed precursors of prolactin cells in the Rathke's pouch at late stages of its formation and for their regional localization in the cephalic part of the anlage. This localization is in correspondence with the distribution of differentiated cells of this type in definitive adenohypophysis. PMID- 2095484 TI - [Common antigens of oval cells and cholangiocytes in the mouse. Their detection by using monoclonal antibodies]. AB - Monoclonal antibodies (MAb) were produced against antigens (Ag) of oval cells isolated from the preneoplastic murine liver. To suppress the immune response to major antigens common with hepatocytes, the principle of anti-idiotype immunization was employed. Characteristics of three MAb reacting selectively with the foci of oval cell proliferation are described. MAb A6 and G7 detected two different antigens (Ag A6 and Ag G7, respectively) common for oval cells and cholangiocytes. Ag A6 was also found in normal parenchyma (in membranes of single hepatocytes adjacent to portal veins), in the preneoplastic liver (in hepatocytes formed de novo) and in some hepatoma cells. Ag G7 was not detected in hepatocytes. MAb E5 stained the matrix in the areas adjacent to oval cells and large bile ducts. All the three Ag were widely distributed in normal tissues of mice. The significance of the detected Ag as markers of murine liver epithelial cell lines and stages of their differentiation is discussed as well as the possible relationship between Ag A6 and Ag of human blood groups. PMID- 2095485 TI - [The oxidation of different substrates by liver mitochondria from rat pups in early postnatal development]. AB - We have studied the respiratory ratio of liver mitochondria during oxidation of substrates of the carbohydrate and lipid metabolism in newborn rats and during early postnatal development. High rate of respiration coupled with the synthesis of ATP from ADP and phosphate has been found during oxidation of carbohydrate substrates (pyruvate + malate); however, caprilate, a substrate of lipid metabolism, does not support such respiration. However, in the young rats aging from 2 to 30 days utilization of carbohydrate and lipid substrates via the phosphorylating pathway proceeds with similar efficacy. PMID- 2095486 TI - [The school of Lev Aleksandrovich Zil'ber in cancer virology and immunology]. PMID- 2095487 TI - [Electric stimulation of spinal muscles during walking as a method of the treatment of scoliosis]. AB - In the article is summarized the experience of treatment of 15 patients with dysplastic lumbar scoliosis of the II and III degree by the method of electrostimulation of dorsal muscles by means of walking corrector. Stimulation of the given type has been employed as rehabilitation therapy after carrying out of the closed chemonucleolysis for the purpose of muscle jacket restoration. Stimulation of trunk muscles in walking allowed to increase correction and stability of vertebral column distortion. Dynamic observations of patients demonstrated stability of achieved curative effect. Therapy of described type can be employed in complex of conservative treatment of scoliosis. PMID- 2095488 TI - [Early diagnosis of progression of funnel chest in children]. AB - 104 patients with progressive forms of funnel chest deformity of the II-III degree with Ehlers-Danlos-Marfan syndrome, Marfan-like phenotype, isolated funnel chest deformity and unclassified funnel chest deformity of the first degree were subjected to synromologic examination. There were detected 10 dysplastic signs, indicating funnel chest deformity progression: anti-Mongol shape of the eyes, arachnodactyly, high palate, Ehlers-Danlos syndrome, floor of the auricle's dysplasia, dolichostenomely, posture disturbance, mitral valve prolapse, umbilical hernia, wide filter. The results of biochemical examination of collagen metabolite--hydroxyproline++ (the first and the second hydroxyproline++ fraction ratio disturbance, decrease of the first hydroxyproline++ fraction percentage, disturbance of direct correlation between total hydroxyproline++ and percentage of the first hydroxyproline++ fraction)--corroborated the clinical data. PMID- 2095489 TI - [Failure of correction of deformities of the cervical spine after intervertebral spondylodesis]. AB - In an effort to reveal the mechanism and the causes of loss of achieved deformation correction during postoperative period in case of intervertebral spondylodesis of cervical part of vertebral column there has been undertaken an investigation, based on detailed clinical and roentgenologic analysis of 69 operated patients in dynamics, combined with the experimental investigations at the intervertebral spondylodesis model. In all patients there has been stated the loss of originally achieved correction, differing in value and direction. It has been suggested that the main loss of correction is, for the most part, a single stepped and intermittent event, that occurs, as a rule, in the near postoperative period. The system tendency to reach the state of stable equilibrium under the effect of arising external forces turned out to be the mechanism of losses and the main cause is inadequate primary stabilization of the created block. A hypothetic classification of the functional state periods of the operated cervical part of vertebral column has been derived. The main advantages of +ceramic spondylodesis as compared with osteoplastic one have been revealed. There have been determined the necessity of further improvement of endofixative construction and surgical intervention techniques, aimed at the primary stabilization level increase. PMID- 2095490 TI - [Use of demineralized bone sawdust in the treatment of spinal injuries]. AB - The experimental investigation for the purpose of studying the possibility of intervertebral osseous adhesion formation when demineralized osseous sawdust is introduced in the intervertebral disk in case of penetrating fractures of bodies of vertebra has been carried out. In 70% of cases the osseous adhesion is formed at the level of disks which demineralized osseous sawdust was introduced to (adhesion was formed, mainly, as perifocal osseous stratifications). Osseous adhesion, in case of introduction of lekozim to the damaged disk, was noted in 20% of cases (1 animal). Osteogenesis in disks was absent in all observations in the control group. When used in clinics in 12 patients with injuries of vertebral column in 63.6% of them perivertebral osseous connection has been formed during 8 12 months. PMID- 2095491 TI - [Clinico-tactical classification of compression-flexion injuries of the thoracic and lumbar segments of the spine]. AB - In the article is presented classification, which takes into consideration mechanisms and sequence of spinal segment destruction in case of compression flexion violence. On the basis of experimental and clinical data are shown the stages of destruction and their roentgenologic diagnosis, prognostication of some other damages, which are not detected by common methods. Differentiated curative tactics, taking account of necessary restorative measures in correspondence with stages and resolution types, is given. PMID- 2095492 TI - [Aspects of surgery, rehabilitation treatment and medical expert evaluation of spinal cord injuries]. AB - The authors examined 794 patients which endured nonpenetrating backbone traumata at different levels (cervical part--367 patients, thoracal part--186 patients and lumbar part--231 patients). The authors indicate total invalidism of patients with grave injures of spinal cord. Provision of employment of patients with less severe traumata depends, for the most part, upon social activity of invalids. In case of cervical part of vertebral column trauma without spinal cord damage and with surgical treatment the working ability of persons, not engaged in physical labour, can be restored in 4-6 months. Physical labour persons suffer from disablement during 1 year. It is not expedient to extend their doctor's certificate but they should be appointed the 11 group of invalidism by medical and labour examination commission. The same tactics for medical and labour examination should be followed in case of noncomplicated traumata of thoracal part of vertebral column. In case of stable fractures of lumbar part of vertebral column it is recommended to determine temporary disablement with brain work persons up to 6-8 months, and in case of nonstable fractures--8-10 months by doctor's certificate. Occupational employment of physical labour persons is contra-indicated during 2-3 years and therefore in case of difficulties with identical employment provision they are appointed the 3 group of invalidism. PMID- 2095493 TI - [Transposition of scapular muscles in the treatment of injuries of the rotator cuff of the shoulder (RCS)]. AB - An experience of 13 cases of short rotator muscles advancement is reported. These procedures were found to be available in treatment of rotator cuff avulsions with retraction, when anatomical reinsertion or shoe-lace suture after Mclaughlin appeared to be impossible. The authors had performed advancement of the supraspinatus alone in 10 cases and simultaneous advancement of supra-, infraspinatus and teres minor in 3 cases. Only one poor result was obtained that can't but confirm a most high efficacy of the procedures described. PMID- 2095494 TI - [Predicting the outcome in patients with scapulo-humeral periarthritis]. AB - In the article is presented a prognostication table of scapulohumeral periarthrosis outcomes, developed in the process of investigation, which allows to predetermine the possibility of recidivation in these patients depending on the presence and expression degree of revealed inflammatory signs. The tactics of a doctor is determined in prescription of curative and prophylactic measures, concentration, sequence and specificity of which is stipulated by a probability of recurrence in different groups of patients with scapulohumeral periarthrosis. Elaborated scheme of patient control, based on preliminary prognostication of outcomes, has been tested at 150 patients. PMID- 2095495 TI - [Various biomechanical indicators in patients with contractures of the finger joint]. PMID- 2095496 TI - [Reconstruction of the I carpo-metacarpal joint by transplantation of the II metatarsophalangeal joint on the neuro-vascular pedicle]. AB - In the article are presented the results of treatment of a patient with the consequences of severe damage of hand. As the basic method of treatment there was used free microneurovascular autotransplantation of tissue complexes. The main attention was paid to the problem of reconstruction of the I carpometacarpal joint by transplantation of the II metatarsophalangeal articulation on the neurovascular pedicle. There was achieved a favourable anatomic and functional result. There are indicated the advantages of the given method in case of irreversible destruction of the I carpometacarpal joint. PMID- 2095497 TI - [Possibilities of reconstruction of the fingers in relation to individual differences in their topographic-anatomic structure]. AB - On the basis of the results of topographic and anatomical investigation carried out at 44 hands of cadavers are discussed the possibilities of restoration of the first finger by means of movement of damaged fingers on the neurovascular limb. The fundamental methods of surgical technique, developed with regard to the structure of neurovascular formations of the hand and individual variability of their topography, are expounded. PMID- 2095498 TI - [Clinico-roentgenological characteristics of the changes in ischemic Volkmann's contracture]. AB - In the article is presented the study of clinical aspects and roentgenograms of 91 children with Volkmann's contraction. The causes of contraction with 46 patients were supracondylar fractures of arm and with 32--forearm bone fractures. All fractures were associated with massive injures of soft tissues, some of the persons have injures of brachial artery. Tardy or incompletely dissected circular plaster bandage turned out to be a factor of complication. All patients demonstrated typical clinical aspects of acute circulatory disturbance of extremity, in some of them with skin and subcutaneous fat necrosis. Clinical aspects of contraction during residual period were notable for variety of manifestations and depended upon the depth of tissue affection (muscles, tendons, articulations, vessels, bones). The gravity of disease has been aggravated by affection of nerve trunks (66 patients). Roentgenologic picture revealed changes of mutual positioning of articular ends of jointed bones and trophic changes within the bones. Trophic changes were revealed by osteoporosis of different extent, growth disturbances as well as perversion of ossification rate of epiphysis and apophysis of tubular and carpal bones. PMID- 2095499 TI - [Kyphotic-scoliotic deformities of the spine in children and adolescents with Ehlers-Danlos syndrome and their treatment]. AB - In the article are presented the results of observation of 8 patients, aged 4-16 years, with Ehlers-Danlos++ syndrome, one of the most frequent hereditary disease with generalized affection of connective tissue. ++Clinico-roentgenologic characteristic of kyphotic-scoliotic++ deformity of vertebral column indicates its progressive nature, that determines indications for surgical intervention but concomitant changes of cardiovascular system should be considered. Preoperative preparation includes measures for vertebral column mobilization as well as pharmacotherapy with retabolil in combination with ascorbic acid, calcetrine and methyluracil++. Selected method of operative treatment is Harrington-Luck techniques in case of scoliosis prevalence and application of original endocorrector with associated influence at kyphotic component. As a result of treatment scoliosis is corrected, on average, by 49,2% and kyphosis by 62,7%. PMID- 2095500 TI - [Kirner's deformity]. PMID- 2095501 TI - [Changes in electric excitability and metabolism in the muscles of replanted extremity]. AB - The authors have studied the dynamics of variation of redox enzymes in the muscles of replanted extremity in 40 adult dogs, which endured replantation of long-ischemized (18-21 degrees C, 4-6 h) extremities. It was discovered that during the postoperative period of observation (45 days) in the muscles of the replanted extremity are preserved obvious degenerative and dystrophic changes and decrease of metabolic and rehabilitation reaction. On the basis of the obtained data the authors employed the effective pathogenetic therapy. PMID- 2095502 TI - [Functional treatment of congenital clubfoot in infants]. PMID- 2095503 TI - [Antibiotic-resistant cultures and the possibility of developing hospital infection in trauma centers]. AB - Antibiotic sensitivity and relation to typical staphylococcus bacteriophages of 1500 cultures of Staphylococcus and 100 cultures of Gram-negative bacteria, isolated from patients and carriers in clinics and subdivisions of the institute of traumatology and orthopaedics, have been studied. R-plasmids have been isolated from Gram-negative microorganisms, possessing plural resistance to antibiotics and relating to Enterobacteriaceae family. Failed to determine dependence between Staphylococcus cultures, isolated from patients and carriers in order to call them hospital-acquired ones. It has been noted predominance of the 11 phagocyte cultures in orthopaedic clinical picture of children and high percentage (55.1) of Staphylococcus carriage state in the clinical picture of acute traumata. Failed to detect hospital infection under the conditions of traumatologic hospital with application of common methods of bacteriologic investigations. PMID- 2095504 TI - [Injuries of the radius head and neck in children]. PMID- 2095505 TI - [Osteomyelitis of the scapula and its treatment]. PMID- 2095506 TI - [Restorative-reconstructive surgery of the bursal-ligamentous apparatus in chronic lateral instability of the knee joint]. AB - Restorative-reconstruction operations for treatment of chronic lateral instability of knee joint have been worked out. Chronic lateral anterior varus instability is eliminated by restoration of anatomy and biomechanics of anterior cruciate ligament and restructuring of peripheral part of the bursal-ligamentous apparatus by means of creation of fibular lateral ligament and 3 derotators (1 active and 2 passive ones). This operation is indicated as well in case of grave anterolateral instability. Instability of posterior types is treated by reconstruction of precise structure and function of posterior cruciate ligament and restructuring of peripheral part of medial or lateral sections of the bursal ligamentous apparatus (it depends upon the nature of damage) by creation of active and passive derotators. PMID- 2095507 TI - [Diagnosis of flattening of arches of the foot and flatfoot]. PMID- 2095508 TI - [Thermovision in the evaluation of the quality of fitting of acceptable intake sockets of shin prostheses]. AB - The authors investigated the internal surface of the intake socket and thermal reaction of skin surfaces when walking on the crus prostheses by means of thermovision. There has been revealed an obvious improvement of capable-of support stump tissue trophism when walking on the crus prosthesis with full contact socket. The prospects of thermovision application for evaluation of prosthetics quality and in the process of fitting of intake sockets have been determined. PMID- 2095509 TI - [Internal osteosynthesis in pseudarthrosis without inter-fracture tissue dissection]. AB - In the paper is presented the experience of operative treatment of 149 patients with false joints of bones, which were subjected to internal osteosynthesis with preservation of inter-fracture tissues. The operation was carried out in the absence of real danger of suppuration. The most frequently operated were the patients with tibia pseudarthrosis (72.5%), fixed by means of a plate. Adhesion has been achieved with 96.7% of patients. COMPLICATIONS: osteomyelitis (1), skin necrosis (2), fractured fragment dislocation under the action of contractor compression application (2). In the process of treatment of 439 patients by means of internal osteosynthesis with dissection of inter-fracture tissues, separation of bone fractured fragments and medullar cavity opening, adhesion has been achieved with 87.2% of patients. PMID- 2095510 TI - [Biomechanical substantiation of prosthetics of the ankle joint]. AB - In an effort to study the causes of postoperative instability of ankle joint endoprostheses, local mechanical properties of the osseous tissue of tibia and talus were studied in terms of physiological loading on 19 cadaverous preparations in the zones, subjected to resection with the purpose of implant setting. High sensitivity of spongiosa tissue to the local mechanic action and significant reduction of the strength characteristics to the depth from subchondral layer have been noted. It has been ascertained that the main cause of the postoperative instability is the excessively voluminous bone resection, dictated by the structural limitations of the used endoprostheses. Admissible tibia and talus resection zones in case of ankle joint prosthetics have been determined. PMID- 2095511 TI - [Use of UV-irradiated autologous bone marrow in the treatment of bone defects in children]. AB - On the basis of experimental researches has been revealed dose-dependent influence of integral UV-irradiation on osteogenic potential of stromal cells- precursors of bone marrow and determined osteogenesis--stimulating dose (300 J/m2). The technique of photomodified bone marrow application for treatment of osseous defects in children has been worked out. Clinical approval (36 observations) has demonstrated high efficiency of the proposed version of osteoplasty: acceleration of reparative processes, reduction of normal osseous structure restoration terms. PMID- 2095512 TI - [Lengthening and correction of deformation of the femur in children and adolescents using rod and bar-rod apparatus of external fixation]. AB - 55 patients with thigh shortening and deformations have been subjected to 65 operations with the use of the rod-based apparatus with outer fixation. Original arrangement diagrams and indications for application of apparatus with external fixation of different versions are provided. Planned lengthening has been achieved with 54 patients. Decrease of the apparatus mass and dimensions, reduction of operative intervention time period, improvement of conditions of remedial gymnastics carrying out and patient self-servicing are considered as advantages of the rod-based apparatus with external fixation. PMID- 2095513 TI - [Functional treatment of closed fractures of the metatarsal bones]. PMID- 2095514 TI - [Ultrasonic evaluation of biomechanical properties of the interosseus membranes of the forearm. I. Selection of a quality index]. AB - In the article is presented the echographic semiotics of the forearm interosseous membrane, based on the results of 10 forearm examinations. Qualitative echographic parameters, describing the forearm interosseous membrane geometry in different biomechanical situations, have been analysed. It has been determined that the ultrasound echography permits to visualize for certain the forearm interosseous membrane. As the criteria of the membrane geometry can be used such indicators as its area and profile height. Ultrasound echography permits to detect interosseous membrane tissue strain in case of forearm rotation and external compression in interosseous space, due to which its elasticity is evaluated. PMID- 2095515 TI - [Prognostication of expert testimony-labor outcomes in the treatment of open fractures of the shin bones]. AB - In the process of clinical and expert examinations of 202 patients with crus bone open fractures, treated by conservative methods, it has been determined that good and satisfactory results have been obtained with 82 (40.6%) victims. At primary examination 92 (45.5%) patients were given the 11 group of invalidism and 28 (13.9%) patients were given the III group of invalidism. In order to decrease the number of expert mistakes, exclude the cases of unsubstantiated groups of invalidism determination and reduce the duration of the doctor's certificate term for victims of the given category, the authors propose to use 3 variants of prognostication of the expert--labour terminations of these damages. The number of the expert mistakes at primary examination of the patients, owing to the proposed method, has come to only 1.4%. PMID- 2095516 TI - [Pathogenetic aspects of studying clonal properties of bone marrow stromal cells in diseases of the osteoarticular system]. AB - Properties of clonogenic stromal fibroblasts of bone marrow which are precursors of osteo- and chondrogenesis, of patients with different diseases of osteoarticular apparatus have been studied. Peculiarities of their reaction on growth-stimulating influence of nonstromal auto- and xenogeneic cells have been demonstrated. The possibilities of data application for studying of pathogenesis of hereditary osteochondrodysplasias as well as other groups of the skeleton affections are considered. PMID- 2095517 TI - [The state of arthroscopy. Report on the assignment trip to the Federal Republic of Germany ("Karl Storz Endoskope" firm and the orthopedic clinic of the city of Rheinfelden)]. PMID- 2095518 TI - [Our method of surgical removal of congenital wing-shaped folds of the neck]. PMID- 2095519 TI - [A device for "finger" spreading after forearm stump splitting]. PMID- 2095520 TI - [A device for formation of canals in the bones]. PMID- 2095521 TI - [Diagnosis and treatment of diastrophic dysplasia and Larsen's syndrome in the 1st years of life]. PMID- 2095522 TI - [Significance of contrast radiography in the assessment of the state of the muscles and differential diagnosis of extensor contractures of the knee joint]. AB - On the basis of analysis of the roentgen contrast examination of femoral muscles of the patients with extension contractures of knee joint, roentgen systematics of the muscle changes at given pathology is presented and the criteria of differential diagnosis of contractures of different types are proposed. 55 patients (125 examinations) with extension contractures of knee joint (arthrogenic, immobilizing, due to myofascio-tenodesis) of different etiology were subjected to roentgen contrast myography. As a consequence, this offered a means of objective evaluation of the muscle state and enabled one to discover the changes of muscles, specific for contractures in general as well as for each type in particular. The table of roentgenologic signs has been compiled which permits to make differential diagnosis, determine the tactics of treatment, select the type of surgical intervention on the basis of the muscle condition. PMID- 2095523 TI - [Hyperplastic coxarthrosis (clinical aspects, diagnosis and treatment)]. PMID- 2095524 TI - [Classification of congenital clubfoot]. PMID- 2095525 TI - [Characteristics of the development of the proximal end of the femur in conservative treatment of congenital hip dislocation (review of the literature)]. PMID- 2095526 TI - [Insertable orthopedic devices in the treatment of flatness of the anterior section of the foot and valgus deviation of the great toe]. AB - The article draws attention to the urgency of the problem of orthopaedic provision of patients with flatness of anterior section of foot and valgus deviation of the first toe for conservative treatment as well as after surgical intervention. Based on clinical and biomechanical peculiarities of foot, in the institute have been developed insertable orthopaedic devices for mass-produced footwear for mentioned pathology: corrective device with unloading element and curative insole. Orthopaedic articles ensure complex influence upon the foot deforming components, improve redressing effect on the first toe. Mass production is planned for 1991. PMID- 2095527 TI - Performance of three walking orthoses for the paralysed: a case study using gait analysis. AB - Three types of walking orthosis are currently available to enable paralysed people to achieve reciprocal gait. This case study assesses the performance in walking of one patient who was proficient in the use of all three devices. The results of a biomechanical analysis are presented in which comparisons are made between the orthoses in terms of general gait parameters and movement of the lower limbs and pelvis. PMID- 2095528 TI - The Edinburgh-ORLAU prosthetic system to provide reciprocal locomotion in children and adults with complete transverse lower limb deficiency. AB - A novel prosthetic system to provide reciprocal locomotion in children and adults with complete transverse lower limb deficiency is described. This is based on the hip joints from the ORLAU ParaWalker, a system with a proven record of success in the orthotic management of paraplegic patients. The fitting of the prototype system to an eight year old girl is described. This experience shows that the orthotic principles of the ParaWalker, which provides reciprocal locomotion for the paraplegic, is equally applicable to the prosthetic situation. Developments are therefore continuing to improve the design and to enable further fittings. PMID- 2095529 TI - Stiffness and hysteresis properties of some prosthetic feet. AB - A prosthetic foot is an important element of a prosthesis, although it is not always fully recognized that the properties of the foot, along with the prosthetic knee joint and the socket, are in part responsible for the stability and metabolic energy cost during walking. The stiffness and the hysteresis, which are the topics of this paper, are not properly prescribed, but could be adapted to improve the prosthetic walking performance. The shape is strongly related to the cosmetic appearance and so can not be altered to effect these improvements. Because detailed comparable data on foot stiffness and hysteresis, which are necessary to quantify the differences between different types of feet, are absent in literature, these properties were measured by the authors in a laboratory setup for nine different prosthetic feet, bare and with two different shoes. One test cycle consisted of measurements of load deformation curves in 66 positions, representing the range from heel strike to toe-off. The hysteresis is defined by the energy loss as a part of the total deformation energy. Without shoes significant differences in hysteresis between the feet exist, while with sport shoes the differences in hysteresis between the feet vanish for the most part. Applying a leather shoe leads to an increase of hysteresis loss for all tested feet. The stiffness turned out to be non-constant, so mean stiffness is used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095530 TI - Analysis of the swing phase dynamics and muscular effort of the above-knee amputee for varying prosthetic shank loads. AB - The purpose of this study was to determine the effect of varying prosthetic shank mass, while maintaining the mass centre location and moment of inertia, on the swing phase kinematics, kinetics and hip muscular effort of free speed above-knee (AK) amputee gait. Six AK amputees, wearing similar prosthetic designs, had three load conditions applied to their prosthetic shank: 1) Load 0-unloaded (X = 39.1% sound shank mass), 2) Load 1-75%, and 3) Load 2-100% sound leg mass. Despite increases in shank mass from 1.33 to 3.37 kg the AK amputee was able to maintain a consistent swing time and walking speed. As load increased, there were significant changes in the maximum knee and hip displacements, as well as phasic shifting. The prosthetic knee Resultant Joint Moment (RJM) was negligible while the shank was accelerating (periods 1 and 2), but was a major contributor during shank deceleration (periods 3 and 4). During periods 1 and 2 the principle contributors to the shank acceleration (forces resisting excessive knee flexion) were the gravitational moment (S-G) and the moment due to thigh angular acceleration (S-AT). During the periods of shank acceleration (sections 1 and 2), there was not a significant increase in the hip muscular effort. However, during sections 3 and 4, the periods associated with shank deceleration, there were significant increases in the hip muscular effort. The hip muscular effort for the complete swing phase increased as load increased by 36.7% and 71.3% for loads 1 and 2. Despite the significant increases in hip muscular effort, four of the six subjects preferred load 1 condition. PMID- 2095531 TI - An angular alignment measurement device for prosthetic fitting. AB - A device to measure socket/shank angular alignment in a prosthesis equipped with a Berkeley Adjustable Leg is described. Angular alignment in the sagittal plane can be measured over the entire 20-degree range with a repeatability of 1 degree. This device can be a useful prosthetics fitting, teaching, and research tool. PMID- 2095532 TI - Five-year clinical assessment of 14 amalgam alloys. PMID- 2095533 TI - Mercury release from amalgam: a study in vitro and in vivo. AB - Total mercury release from a high-copper and a low-copper amalgam was measured in a study in vitro using atomic absorption spectrophotometry. Conditions of mechanical agitation and sealant coverage were evaluated over time. Mercury release was found under agitation and no-agitation conditions to increase shortly after preparation and then to level off after 24 to 48 hours. No difference in mercury release was observed for either amalgam type. Sealant coverage of amalgam significantly reduced mercury release under agitation conditions. In an experiment in vivo mercury vapor was measured at different times for patients receiving their first amalgam restoration. Sealant coverage was found to significantly reduce mercury vapor after chewing on this restoration compared to a nonsealant-covered amalgam. PMID- 2095534 TI - Two-year evaluation in vivo and in vitro of Class 2 composites. AB - Nineteen class 2 Herculite restorations were evaluated two years after placement. Nine of these were retrieved and examined by clinical inspection out of the mouth. Six of the restorations were then removed and the cavities examined for extent and location of discoloration and secondary caries. Radiolucent defects at the gingival margins were seen in 36% of the teeth. Gaps were evident in 58% of the gingival margins of the retrieved teeth. Secondary caries was diagnosed in four cases, all of them at the cervical margin. Examination of the cavities after removal of the composite resin demonstrated the penetration of the carious process into the dentin. PMID- 2095536 TI - Distinguished Member Award. PMID- 2095535 TI - Fabrication of a crown to fit an existing partial denture using castable glass. AB - In this case report, an accepted technique was used to fabricate a crown to fit an existing removable partial denture in which castable glass was used instead of gold. The use of castable glass allowed the crown to be cast directly from a wax acrylic pattern and eliminated the need for templates to produce accurate facial contours in porcelain. Although castable glass has limitations and cannot be used in all such situations, the material can be used in selected cases where esthetics is important. PMID- 2095537 TI - Longitudinal evaluation of caries patterns form the primary to the mixed dentition. AB - The purpose of this study was to develop a model describing the sites and patterns of dental caries in the mixed dentition for children with one of five caries experiences in the primary dentition. Dental records were used from 317 children followed an average of 7.8 years in private pediatric dental offices to assess specific caries experiences in children from early primary dentition to middle or late mixed dentition. Eighty-four per cent of the children who were caries-free in the primary dentition remained so in the mixed dentition. Children with the pit and fissure caries pattern in the primary dentition were more likely to develop smooth surface caries of primary teeth in the mixed dentition (32%) than caries-free children (14%, X2 = 5.6;P less than 0.05). For children with molar-approximal lesions in the primary dentition, 57% developed lesions on additional molar-approximal surfaces in the primary teeth in the mixed dentition. Children with the faciolingual pattern (baby bottle tooth decay) were at the highest risk of any group for developing additional carious lesions. The model could serve as a basis for a prospective study. PMID- 2095538 TI - Comparison of triazolam to a chloral hydrate/hydroxyzine combination in the sedation of pediatric dental patients. AB - The purpose of this study was to compare the effectiveness of triazolam to chloral hydrate with hydroxyzine when sedating young children for dental treatment. Twenty children, age 21 to 74 months, with a mean age of 44 months, were given triazolam. Twenty children, age 23 to 64 months, with a mean age of 42 months, were given chloral hydrate with hydroxyzine. The children were given an elixir of either .02 mg/kg triazolam or 40 mg/kg chloral hydrate with 25 mg hydroxyzine. All subjects received 50% nitrous oxide and were restrained with a Papoose Board. The sedations were videotaped and evaluated by two pediatric dentists not involved in the study. They rated the success of the sedations by degree of sleep, crying, body movements, and overall behavior. Time until onset of action of the agents given, oxygen saturation of arterial blood, and heart rate were measured. The vital signs were consistent for the two groups. There was no statistical difference in the effectiveness of sedation between the two groups. PMID- 2095539 TI - Comparison of a chloral hydrate/hydroxyzine combination with and without meperidine in the sedation of pediatric dental patients. AB - The purpose of this study was to compare the effectiveness of a chloral hydrate/hydroxyzine combination with and without meperidine in the sedation of pediatric dental patients. Twenty children were given 40 mg/kg chloral hydrate and 25 mg hydroxyzine, and 20 children were given 40 mg/kg chloral hydrate and 25 mg hydroxyzine and 0.5 mg/kg meperidine. All children were between the ages of 24 and 60 months and all medications were given orally 1 hr before treatment. The children received 50% nitrous oxide for the entire procedure. All children were restrained in a Papoose Board. The patients were videotaped and their behavior was rated by two independent pediatric dentists using the Houpt Scale. The independent evaluators did not know which sedation regimen had been used. They rated success of the sedations by degree of sleep, crying, body movements, and overall behavior. Oxygen saturation of arterial blood, and heart rate also were measured. The vital signs were consistent for the two groups. There was no significant difference in the effectiveness of the two drug regimens. PMID- 2095540 TI - In vitro evaluation of fluorescein for testing the permeability of white spots on tooth enamel. AB - This investigation demonstrates the reliability of fluorescein for detecting the permeability of incipient dental caries (white spots). Artificial white spots were created on the buccal surface of 12 human bicuspids by viscous lactic acid (pH 4). Permeability of these lesions was assessed and reassessed before and after 24 and 48 hr of acid challenge using two disclosants: sodium iodide and sodium fluorescein. Estimates obtained from both disclosants showed that the microvoid volume approximately doubled as the decalcification time doubled. The two disclosants exhibited good intraclass reliability and their scores were correlated (r = 0.69 to r = 0.91). However, only fluorescein disclosed the extent of porous white spot lesions. Thus, fluorescein should be considered when the objective is to detect the location and permeability of incipient lesions. PMID- 2095541 TI - Variables influencing Streptococcus mutans testing. AB - When saliva is sampled to estimate S. mutans, variables may influence the results. The purpose of the present study was to assess the reliability of the tongue depressor for saliva sampling, and whether the sampling time during the day influences S. mutans counts. The study population consisted of 27 children, between 24 and 66 months of age. Samples of unstimulated saliva were gathered on tongue blades four times during the day for each subject. Paired samples representing both sides of the tongue blades were inoculated onto elevated agar plates containing a selective medium, and anaerobically incubated at 37 degrees C for 48 hr. After examining 76 paired samples of saliva, no significant differences in S. mutans counts were found between sides of the spatula, suggesting that the sampling technique was suitable. Analysis of variance showed significant differences within each subject over the four sampling times (P less than .01). A significant difference was found between subjects' daily averages (P less than .05). PMID- 2095542 TI - Dilaceration of a primary maxillary incisor associated with neonatal laryngoscopy. AB - Neonatal laryngoscopy and endotracheal intubation often are required for prematurely born, low birthweight children. Previous studies have shown that these procedures are associated with a high prevalence of enamel hypoplasia of the maxillary anterior teeth. The present case report, which describes dilaceration of a left maxillary primary central incisor probably resulting from laryngoscopy, strongly supports the hypothesis that irreversible trauma to the dentition may result from endotracheal intubation. PMID- 2095543 TI - [Molecular and informative mechanisms of genome transmission to to the progeny]. PMID- 2095544 TI - [Prenatal diagnosis and characteristics of chromosome aberrations in families with genetic risk]. AB - Characteristics of the chromosomal aberrations diagnosed in 959 prenatal tests in the II trimester of pregnancy is presented. Chromosomal aberrations were diagnosed in 33 tests (3.4%). Twenty one out of these aberrations (2.2%) were of labile character. Six aberrations resulted from the parental segregation, translocation or chromosomal inversion. In 12 cases fetus inherited stable aberration from one of parents. It amounted to 1.2% of all tested cases. Chromosomal aberrations were diagnosed in 2.7% cases tested due to the risk related to the mother's age. Half of them was trisomy of chromosome 21. Chromosomal aneuploidy in the progeny of families with a child with the same abnormality was diagnosed in 1.6% of cases. Chromosomal mosaicism was diagnosed in 2.2% of cases including 0.2% of cases with true mosaicism and 1.98% of cases with pseudomosaicism. Incidence and type of the diagnosed chromosomal aberrations coincided with foreseen aberrations for each group of the genetic risk. PMID- 2095545 TI - [Favism in Polish families]. AB - Four cases of fawism are presented. The disease was seen in one male patient, one homozygote and in 3 carriers of G6PD deficit. Diagnostic procedures, course of the haemolytic crisis in these patients, and possibility of prophylaxis in the families with fawism are discussed. PMID- 2095546 TI - [Treatment of anemia in patients with renal failure using erythropoietin obtained by genetic recombination]. AB - In 5 haemodialyzed patients with end-stage renal failure an effect of human recombinant erythropoietin (r-huEpo) on haemoglobin, haematocrit and iron metabolism was studied. After 12 weeks of the treatment, a significant increase in haemoglobin and haematocrit but significant decrease in plasma ferritin were noted. During r-huEpo treatment, one patients presented clinical symptoms of increased blood coagulation whereas another patients an increase in blood pressure. r-huEpo did not influence leukocytes and platelets count as well as liver function tests. Our results suggest, that r-huEpo is highly effective and safe in the treatment of anaemia in patients with chronic uraemia. Iron metabolism, blood pressure and blood coagulation must be monitored during therapy with r-huEpo. PMID- 2095547 TI - [A case of Ellis-van Creveld syndrome]. AB - A case of the Ellis-van Creveld syndrome in a 18-year girl with congenital disturbances is presented. In the patients described they were coexisting with insulin dependent diabetes mellitus. PMID- 2095548 TI - [Delayed puberty in an 18-year-old female patient with late diagnosis of celiac disease]. AB - A case of a 18-year female patient is presented. The patient suffered from certain symptoms of malabsorption syndrome. She was also retarded sexually. Celiac disease was diagnosed according to ESPGAN criteria. Gluten -free diet produced body weight increase, pain relief, improved well-being and normal menstruation. PMID- 2095549 TI - [Alloimmune neonatal granulocytopenia caused by anti-NA1 antibodies]. AB - Two cases of neonatal alloimmune granulocytopenia due to fetomaternal incompatibility with granulocyte-specific antigen NA1 are presented. The diagnosis was based on the detection of anti-NA1 alloantibodies in maternal and neonates sera in leukoaglutination and immunofluorescence tests with granulocytes. Both children (twins) had severe granulocytopenia and unfortunately died. PMID- 2095550 TI - [Congenital angioneurotic edema in an 11-year-old girl]. AB - A case of a 11-year girl with the inherited angioedema is presented. Lack of improvement following antiallergic therapy and familial history of the disease were the base of studies leading to the diagnosis of this rare syndrome. Preliminary diagnosis was confirmed by C1q inhibitor and blood level of C4 assays. PMID- 2095551 TI - [New theories on the role of genetically determined alpha 1-antitrypsindeficiency in the development of pulmonary emphysema]. PMID- 2095552 TI - [H-B-VAX II]. PMID- 2095553 TI - [Natural anti-mutagenic and anti-carcinogenic substances]. PMID- 2095554 TI - Structure and evolution of 5S rRNA genes. PMID- 2095555 TI - [Prenatal diagnosis: a chance? risk? dilemma?]. PMID- 2095556 TI - [New types of plasminogen activators]. PMID- 2095557 TI - [High-molecular-weight complexes of amino acyl T RNA synthetases]. PMID- 2095558 TI - [Methods of DNA mutagenesis in vitro]. PMID- 2095559 TI - Optimized inhalation aerosols. II. Inertial testing methods for particle size analysis of pressurized inhalers. AB - Pressurized metered dose inhaler (MDI) output from three different albuterol formulations was characterized using three inertial separation devices. Results were compared for the Delron six-stage cascade impactor (DC16), the Andersen Mark II eight-stage impactor (AC18), and Copley's twin-stage liquid impinger (LI). None of the devices tested in this study was ideal in all respects. All devices could differentiate between formulations in terms of respirable doses (albuterol amount with aerodynamic diameters less than 5.5 through 6.4 microns). Only the high-flow rate LI could differentiate among all three formulations when data were presented in terms of respirable percentage (RP) of drug collected. Values for RP were in excellent agreement for the independently calibrated impactors when the same evaporation chamber was used atop the impactors. The LI appeared to overestimate values for RP in vivo. Results are discussed in light of the debate surrounding the revision of USP aerosol testing requirements. Rigorous specifications for evaporation chambers and methodologies are necessary for meaningful inter- and intra-laboratory comparison of results when any of these devices are used. PMID- 2095560 TI - Analytical approaches to the study of monoclonal antibody stability. AB - The stability of two purified monoclonal antibodies, MN12 and WT31, was investigated. The monoclonal antibodies were incubated for 32 days at different pH values (ranging from 3.0 to 10.0) at 4 and 37 degrees C. Various analytical methods were used to assess changes in physicochemical properties of the proteins. The monoclonal antibodies were more susceptible to degradation at 37 degrees C than at 4 degrees C. At low pH irreversible precipitation occurred. Decomposition of the proteins was enhanced at increasing pH values in the alkaline range. This was concluded from mouse IgG-specific and antigen-specific enzyme-linked immunosorbent assays, flow cytometry, analytical gel permeation chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, and immunoblotting. No substantial change in the apparent affinity constant of MN12 was observed, as determined by an affinity enzyme linked immunosorbent assay. Fluorescence spectra, fluorescence polarization values, and fluorescence quenching parameters of MN12 and WT31 were not substantially affected, indicating that no major irreversible conformational changes had occurred. It was concluded that each of the techniques used has only limited value for stability assessment of monoclonal antibodies and, hence, that the application of several analytical techniques is essential to gain insight into monoclonal antibody stability. PMID- 2095562 TI - The pharmacokinetics of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in the rat. AB - Hydroxypropyl-beta-cyclodextrin was analyzed by HPLC using postcolumn complexation with phenolphthalein and negative colorimetric detection, with a detection limit of 20 micrograms/ml. The pharmacokinetics of beta-cyclodextrin and of hydroxypropyl-beta-cyclodextrin were studied after intravenous administration to permanently cannulated rats. The pharmacokinetic behavior of both cyclodextrins was similar to that of inulin, showing rapid distribution over extracellular fluids. Elimination occurred through glomerular filtration. When a dose of 200 mg/kg beta-cyclodextrin was administered the elimination rate was decreased, probably as a result of nephrotoxicity of beta-cyclodextrin. Within 24 hr after administration most of the cyclodextrin dose was recovered unchanged in urine. After oral administration, only insignificant amounts of intact beta cyclodextrin were absorbed from the gastrointestinal tract. PMID- 2095561 TI - An experimental model for measuring middle ear antimicrobial drug penetration in otitis media. AB - Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean +/- SD volume of 2.09 +/- 0.08 ml and a mean +/- SD surface area of 14.41 +/- 1.48 cm2. To measure the apparent rate constant (Kc) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean Kc +/- SD for amoxicillin was 0.118 +/- 0.013 hr-1, that for a trimethoprim 0.461 +/- 0.090 hr-1, and that for sulfamethoxazole 0.265 +/- 0.062 hr-1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the Kc +/- SD increased for all three drugs (P less than 0.05): amoxicilin to 0.286 +/- 0.089 hr-1, trimethoprim to 0.662 +/- 0.118 hr-1, and sulfamethoxazole to 0.411 +/- 0.056 hr-1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142%). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44%), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095563 TI - Column-switching high-performance liquid chromatographic (HPLC) determination of hydrochlorothiazide in rat, dog, and human plasma. AB - A fully automated HPLC assay for hydrochlorothiazide in plasma has been developed using a column-switching technique. The method involves direct injection of plasma to the extraction column for sample cleanup followed by switching onto the analytical column. Good precision, accuracy, and linearity were obtained over a range of 25 to 2000 ng/ml in rat, dog, and human plasma. The column-switching method has also been validated by comparison with a conventional HPLC method requiring a cumbersome plasma extraction procedure. Since the method is simple, rapid, and reproducible, it is useful for determination of hydrochlorothiazide levels in animal and human plasma. PMID- 2095564 TI - Chiral amines derived from 2-arylpropionic acids: novel reagents for the liquid chromatographic (LC) fluorescence assay of optically active carboxylic acid xenobiotics. AB - For the enantiospecific analysis of optically active carboxylic acids, the availability of readily detectable coupling components is desirable, but highly fluorescent chiral amines are rare. From activated enantiomers of fluorescent 2 arylpropionic acids fluorescent chiral amines were synthesized via Curtius degradation, i.e., under formation of the acyl azide, the isocyanate, and finally, the amine. The formation of isocyanates and of amine hydrochlorides led to an inversion of the direction of rotation of polarized light. Amines derived from R- and S-flunoxaprofen, R- and S-naproxen, and R/S-benoxaprofen were characterized. The amines were found to be applicable for the chiral separation of carboxylic acids (such as 2-arylpropionic acids) as diastereomeric derivatives via high-performance liquid-chromatographic (normal and reversed-phase) and thin layer chromatographic techniques. PMID- 2095566 TI - Amorphous-to-crystalline transformation of sucrose. AB - The transformation of amorphous sugar in the form of lyophilized spheres into crystalline sucrose was studied. The lyophilisate, when exposed to moist atmospheres, picks up moisture to a constant weight. The amount of moisture addition is a function of relative humidity of the atmosphere and temperature. The loose "lyophilisate structure" collapses to form a denser amorphous phase ("hydrated amorphate"). After a lag time which varies with relative humidity of the atmosphere and temperature, the hydrated amorphate loses moisture (weight) and, in the process, forms crystalline sucrose. The phase nature of the hydrated amorphate is equivalent to an aqueous solution that is supersaturated with respect to crystalline sucrose. A model was developed for the lag time which accounts for the experimental results. PMID- 2095565 TI - Sesquiterpene lactones and other constituents from a cytotoxic extract of Michelia floribunda. AB - The pentane and CHCl3 fractions of a crude extract of Michelia floribunda exhibited cytotoxic activity when tested in KB and P388 tumor cell cultures. Repeated chromatography led to the isolation of three cytotoxic sesquiterpene lactones (costunolide, parthenolide, and santamarine) and a cytotoxic isoquinoline alkaloid (liriodenine). Inactive sesquiterpene lactones obtained during the course of this study included dihydroparthenolide and two new glucosides of dihydrotamaulipin A and dihydroreynosin (1 and 2). The structures of these new compounds were determined through interpretation of their spectroscopic data including 2D-NMR spectroscopy. Syringin was also isolated from the extract. PMID- 2095567 TI - Aluminum compounds used as adjuvants in vaccines. AB - The structure of nine commercially manufactured aluminum-containing adjuvants was investigated by X-ray diffraction, infrared spectroscopy, transmission electron micrography, and energy dispersive spectrometry. Seven samples which were labeled as aluminum hydroxide were identified as boehmite, a crystalline aluminum oxyhydroxide [AlO(OH)]. However, the degree of crystallinity varied between the samples. Two samples which were labeled as aluminum phosphate were found to be amorphous aluminum hydroxyphosphate. Buffer anions and sulfate anions substitute for hydroxyls in the amorphous aluminum hydroxide formed by the in situ alum precipitation method. Finally, the aluminum-containing adjuvant in diphtheria and tetanus toxoid, U.S.P., produced by three manufacturers was characterized. PMID- 2095568 TI - Cytotoxicity of three novel fluoropyrimidines in cultured L1210 murine lymphocytic leukemia cells. AB - Cultured L1210 murine lymphocytic leukemia cells were used to compare metabolic activation and cytotoxicity of 5-fluorouracil (FU), Ftorafur (FT), and three novel FU-sulfur analogues. These analogues, 1-(2'-tetrahydrothienyl)-5 fluorouracil (FUS), 1-(2'-tetrahydrothienyl)-5- fluorouracil-1'-oxide (FUSO), and 1-(2'-tetrahydrothienyl)-5-fluorouracil-1'-1'-dioxide (FUSO2), have yet to be fully evaluated for potential therapeutic value based on in vitro cytotoxicity. The role of these FU analogues as prodrugs was evaluated by comparing metabolism of normal pyrimidine pathways and activation by hepatic mixed function oxidases (MFO). Significant differences in biochemical activity and cytotoxicity were measured between FU and FU analogues. FU and FU analogues were cytotoxic to L1210 cells (63-92% growth inhibition of 100 microM concentrations after 72 hr of incubation). However, at equimolar concentration cytotoxicity of the FU analogues after MFO activation (56-66% growth inhibition) was greater than FU (47% growth inhibition). Hypoxanthine, a purine precursor, did not significantly alter fluoropyrimidine cytotoxicity with or without MFO. Thymidine and uridine, pyrimidine precursors, reduced FT and FUS cytotoxicities in the presence (27, 40%) and absence (25, 15%) of MFO but did not modify FU, FUSO, or FUSO2 cytotoxicities. PMID- 2095569 TI - Cutaneous pharmacodynamics of transdermally delivered isosorbide dinitrate. AB - Laser doppler velocimetry (LDV) has been used to assess the cutaneous pharmacodynamics of isosorbide dinitrate (ISDN) following transdermal delivery of the drug from prototypal patches. The delivery systems, which were saturated with ISDN, (a) produced various degrees of skin occlusion and (b) spanned a six-fold range of adhesiveness. The patches were applied to the ventral forearm skin of 10 healthy volunteers and the local ISDN-induced increase in local skin blood flow was determined using LDV by locating the probe in a central hole in the delivery system. Measurements were made for 1.5 hr and the pharmacodynamics were quantified by (i) the maximum LDV response and (ii) the area under the LDV response versus time curve. These parameters were not sensitive to patch occlusivity. They were significantly (P less than 0.01) dependent on patch adhesiveness, though, and decreased with increasing adhesion. Although this observation suggested that ISDN diffusion through the adhesive could determine, at least in part, the rate of drug delivery, it was subsequently demonstrated that ISDN release (in vitro, into a perfect "sink") was unaffected by the level of cross-linking in the adhesive polymer. Because the drug was present in all systems at unit thermodynamic activity, these results cannot be explained on the basis of altered ISDN partitioning at the device-stratum corneum interface. We speculate that the in vivo-in vitro discrepancy may be due to the efficiency of skin contact achieved by different adhesives: that is, the more adhesive, less flexible systems make poorer contact with the skin surface, thereby decreasing the effective surface area of drug delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095570 TI - A method to predict the percutaneous permeability of various compounds: shed snake skin as a model membrane. AB - Penetration of various compounds through shed snake skin was measured in vitro to examine the effect of lipophilicity and molecular size of a compound on permeability through this model membrane. The permeabilities were found to be controlled by the lipophilicity and the molecular size of the permeant. The smaller and the more lipophilic the compound, the greater the permeability. Equations have been developed to predict the permeability from the molecular weight and the distribution coefficient of a compound. Further, the lipophilicity of shed snake skin is similar to that of human skin and the response of shed snake skin to the molecular size of a permeant is more similar to human skin than to hairless mouse skin. Considering the similarities between shed snake skin and human stratum corneum in terms of structure, composition, and permeability characteristics, the same considerations may apply to permeability through human stratum corneum. PMID- 2095571 TI - Investigations on the percutaneous absorption of the antidepressant rolipram in vitro and in vivo. AB - In vitro experiments using full-thickness human skin showed that it was feasible to deliver therapeutic amounts of the new antidepressant drug rolipram. Simple transdermal devices were constructed, and the presence of isopropyl myristate (IPM) in a silicone adhesive (Dow Corning X7-2920) enhanced the flux across excised human skin. The steady-state fluxes from adhesive mixtures containing 0, 5, and 10% IPM were 3, 5.2, and 6 micrograms/cm2/hr, respectively. The in vitro experiments were confirmed in a clinical study involving six healthy male volunteers. The formulations tested were an alcoholic solution and adhesive patches containing 5 and 10% IPM. The dose of drug administered was 0.5 mg/cm2 and the device size 25 cm2. Blood samples were withdrawn over a 24-hr period and analyzed using radioimmunoassay. The topical applications were well tolerated, with only mild or no side effects. A lag time of approximately 2 hr was found for the detection of rolipram in the plasma (detection limit, 50 pg/ml). Interindividual variations both for the peak drug levels and throughout the delivery were quite high but this magnitude of variation has been observed in many other transdermal studies. Plasma levels between 1 and 2 ng/ml were found for all formulations and the AUC0-30 hr was significantly higher for the patch containing 5% IPM. PMID- 2095572 TI - Mechanism of L-alpha-methyldopa transport through a monolayer of polarized human intestinal epithelial cells (Caco-2). AB - The Caco-2 model system (Hidalgo et al., Gastroenterology, 96:736-749, 1989), which is a monolayer of polarized intestinal epithelial cells grown onto a porous polycarbonate membrane, was used to study the mechanism of transcellular transport of an antihypertensive agent, L-alpha-methyldopa (L-alpha-MD). The results showed that the transport of L-alpha-MD was pH, glucose, concentration, and temperature dependent, and it could be inhibited by metabolic inhibitors (e.g., 2,4-dinitrophenol) and by amino acids (e.g., L-phenylalanine) which have an affinity for the large neutral amino acid (LNAA) carrier. In addition, the apparent kinetic constants describing the transcellular transport of L-alpha-MD were altered depending on the time interval between feeding the cells and the transport experiments (postfeeding time, PFT). The apparent maximum carrier flux (Jmax) of L-alpha-MD was significantly increased (from 155 to 547 pmol/mg protein/min) when PFT was prolonged from 8.5 to 56 hr. These results indicated that the transcellular transport of L-alpha-MD through the polarized Caco-2 cell monolayer was carrier mediated via the LNAA carrier. The similarities in the characteristics of L-alpha-MD transport exhibited by the Caco-2 model system and other intestinal models in vitro further substantiate the usefulness of this cell culture model for studying the intestinal transport of nutrients and drugs. PMID- 2095573 TI - Optimization of topical therapy: partitioning of drugs into stratum corneum. AB - To optimize a topical formulation for therapeutic effect generally implies that the flux of drug into the skin be maximized. This requirement means that the product of drug concentration in the vehicle (Cv) and drug partition coefficient (PC) between stratum corneum (SC) and vehicle be as large as possible. While Cv is a formulation variable which can be easily manipulated up to the drug's saturation solubility, PC is a parameter that is difficult to predict a priori. However, there is no question that an ability to evaluate PC would greatly facilitate the efficient screening of drugs and formulations. We have measured the SC/water and SC/isopropylmyristate (a model lipophilic vehicle) PCs of seven drugs; acitretin, progesterone, testosterone, diazepam, estradiol, hydrocortisone, and caffeine, SC/water PCs were determined as a function of the following variables: (i) initial drug concentration in the vehicle, (ii) length of equilibrium, (iii) SC source and preparation technique, and (iv) SC delipidization. The data obtained were reproducible and physicochemically consistent, and they show that useful partitioning information from both aqueous and nonaqueous vehicles can be obtained with the biological tissue of greatest relevance. The SC/water PCs of the steroids were in reasonable agreement with previous measurements. A facile approach to an integral determinant of formulation optimization is suggested, therefore, by these observations. PMID- 2095574 TI - Solubility and ionization behavior of the antiarrhythmic 4-hydroxy-N-phenyl-3,5 bis(1-pyrrolidinylmethyl)benzamide dihydrochloride (DuP 923). PMID- 2095575 TI - Topical irritation of the gastrointestinal tract. PMID- 2095576 TI - Stimulation of cultured iridophores by amphibian ventral conditioned medium. AB - That the ventral integument of adult frogs (Rana pipiens) contains factor(s) that stimulate iridophore expression (adhesion, morphologic appearance, proliferation) was demonstrated on iridophores derived from tadpoles of R. pipiens and Pachymedusa dacnicolor, and maintained in primary culture in a growth medium based upon Leibovitz's L-15. Experimental growth medium (VCM) conditioned by a one-hour exposure to pieces of ventral skin of adult R. pipiens induced iridophores to assume a broad and stellate appearance, to form confluent sheets, and to proliferate over a nine-day period. Iridophores in control medium assumed long thin profiles, detached easily, and exhibited no signs of proliferation. Unknown cells containing reflecting platelets and unusual other organelles appeared uniquely in chromatophore cultures of P. dacnicolor in VCM. The intense stimulation of iridophore expression in VCM is consistent with the known inhibitory effect of this medium on melanization and with its purported role in the determination of dorsal/ventral pigment patterns of amphibians. The results are discussed in terms of a prevailing theory about pigment cell origins and development. PMID- 2095577 TI - [Epidemiology of ischemic heart disease]. PMID- 2095578 TI - [Value of enzymatic studies in the diagnosis of myocardial infarction]. PMID- 2095579 TI - [Use of percutaneous transluminal coronary angioplasty in the acute period of myocardial infarction]. PMID- 2095580 TI - [Phosphocreatine kinase and its multiple forms as a clinically useful indicator]. PMID- 2095581 TI - [Methods of analysis of creatine kinase isoenzymes and isoforms with special reference to CK MM]. PMID- 2095582 TI - [Creatine kinase and its isoenzymes--analytical reliability and diagnostic value]. PMID- 2095584 TI - Decreased collagen concentration in rat uterine implantation sites compared with non-implantation tissue at days 6-11 of pregnancy. AB - Collagen concentrations at implantation sites in the rat uterus were found to be significantly decreased compared with concentrations in adjacent non-involved uterine tissue in early pregnancy (75% by Day 11). The decrease in collagen was most marked in primary decidua and was also observed to a lesser extent (20%) in myometrium at the implantation site. There was a decrease of 20% in the concentration of total proteins at Day 7 (as measured by the ninhydrin method) and a slight increase in water content (2%) at Days 6 and 7. The differences in total protein and water content were transient, but the difference in collagen was maintained throughout early pregnancy. The localized changes in collagen content observed in this study, along with previously reported morphological changes in fibrillar and basement-membrane collagens in the uterus, give support to a theory of remodelling in early pregnancy involving simultaneous synthesis and degradation of extracellular proteins during decidualization. PMID- 2095583 TI - [Hemodynamic disorders of pulmonary circulation and the right ventricle and the extent of myocardial infarction measured by the CK and CK MB activities]. PMID- 2095585 TI - Rapid cryopreservation of sheep embryos by direct transfer into liquid nitrogen vapour at -180 degrees C. AB - The in vitro survival of control and rapidly cryopreserved sheep embryos was examined as a function of the duration of exposure to a vitrification medium (25% glycerol + 25% propylene glycol). Embryos in late morula to late blastocyst stages were permeated by a mixture of 10% glycerol + 20% propylene glycol for 10 min at 18-23 degrees C and then exposed to the vitrification medium for 0.5, 1, 2 or 4 min at 18-23 or 4-12 degrees C. The cryoprotectants were removed without cryopreservation (control embryos) or after rapid cryopreservation by direct transfer into liquid nitrogen vapour at -180 degrees C. The duration of exposure to the vitrification medium at 18-23 degrees C affected the in vitro survival rate of control embryos (P = 0.06) but had no effect on the survival of rapidly cryopreserved embryos. However, at 4-12 degrees C the duration of exposure affected the survival of cryopreserved embryos (0.5 min: 64%, 18/28; 1-4 min: 43%, 34/80; P = 0.074). Overall, the in vitro survival rate of control and cryopreserved embryos increased with advancing development from late morulae (36%) to late blastocysts (70%). The in vivo survival of embryos that had been exposed to the vitrification medium for 0.5 min at 4-12 degrees C and then vitrified was tested. The rate of development to term was 11% (4/35) for late morulae or early blastocysts and 32% (6/19; P greater than 0.1) for blastocysts to hatching blastocysts. These results showed that sheep embryos can be successfully cryopreserved by a simple, rapid procedure. PMID- 2095586 TI - In vitro embryo culture in the production of identical merino lambs by nuclear transplantation. AB - This study examined the viability of embryos developed in vitro from 8- to 16 cell stage blastomeres fused with enucleated oocytes. Of 209 blastomeres recovered and subjected to manipulation and electrofusion procedures, 190 (91%) fused successfully, with 86 (45%) of those undergoing cleavage up to the 4- to 16 cell stage when cultured for 66 h in a synthetic oviduct fluid medium. The viability of the embryos was examined by transferring them to recipient ewes and determining the ewes' pregnancy status by ultrasound on Day 45. Of 86 embryos transferred, 14 developed to fetuses in 8 of the 36 recipients, including four sets of identical twins and one set of quads. In contrast, with uncultured and unmanipulated embryos, 15 fetuses developed from 19 embryos transferred at a similar stage of development. The viability of embryos derived from manipulated zygotes cultured in vitro was comparable to that previously reported for studies employing in vivo culture, indicating the potential of in vitro culture systems based on a simple medium for nuclear-transplantation embryos. PMID- 2095587 TI - In vitro assessment of the viability of sheep zygotes after pronuclear microinjection. AB - Microinjected sheep zygotes were cultured in synthetic oviduct fluid medium (SOFM) for either 1 or 3 days and their subsequent developmental capacity was compared with that of microinjected zygotes cultured in vivo. Two experiments were carried out, using zygotes microinjected with one of three gene constructs containing the CysE and CysM genes from Salmonella typhimurium. In Experiment 1, microinjected zygotes were allocated to one of three treatments: (1) immediate transfer to recipient ewes (in vivo culture) followed by recollection 1 or 3 days later and subsequent transfer of viable embryos to other recipient ewes, (2) culture in SOFM (in vitro culture) for either 1 or 3 days before transfer to recipient ewes, and (3) immediate transfer to recipient ewes without subsequent interference. Recipient ewes were slaughtered on Day 14 of pregnancy and the number of elongated conceptuses determined. Although fewer zygotes failed to divide during in vitro culture than during in vivo culture, there were, overall, no significant differences between treatments in the percentage of zygotes that developed into elongated conceptuses (32.6-50.0%). In Experiment 2, microinjected zygotes were transferred immediately to recipient ewes or cultured in vitro for either 1 or 3 days before transfer. The number of fetuses per ewe on Day 50 of pregnancy and the number of lambs delivered per ewe were recorded. Neither the percentage of recipient ewes that became pregnant (overall 114/166, 68.7%) nor the percentage of zygotes that developed into lambs (overall 186/803, 23.2%) was significantly influenced by the culture treatment or by the gene construct microinjected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095588 TI - Use of oocytes that failed to be fertilized in vitro to study human sperm-oocyte interactions: comparison of sperm-oolemma and sperm-zona pellucida binding, and relationship with results of IVF. AB - A test for human sperm binding to the oolemma was developed with oocytes that failed to be fertilized in vitro. The zonae pellucidae of the oocytes were removed under a dissecting microscope by brief exposure to dilute HCl (pH 2.5 3.0) in 0.9% NaCl. The zona-free oocytes (ZFOs) were incubated with a mixture of equal numbers of motile sperm from men to be tested and fertile donors. The sperm was differentially labelled with fluorescein or rhodamine and the results expressed as a ratio of the number of test to control sperm bound to several ZFOs in order to control for variability in the ability of the oolemma to bind sperm. The number of sperm bound to the oolemma increased with time and sperm concentration. The sperm-oolemma binding ratio determined for 32 patients undergoing in vitro fertilization (IVF) was significantly correlated with the sperm-zona pellucida (ZP) binding ratio but was not correlated with other sperm tests. The sperm-oolemma binding ratio was also related to the IVF rate, but this was not significant if the sperm-ZP binding ratio was included in the logistic regression model. Only four of the 32 patients had failure of fertilization in vitro. The human sperm-oolemma binding test may be useful for studying the interaction between gametes, but the test is unlikely to be as useful clinically as the sperm-ZP binding test for predicting fertilization in vitro. PMID- 2095589 TI - Developmental capacity of mechanically bisected mouse morulae and blastocysts. AB - Mouse embryos were mechanically bisected at the morula, early blastocyst or expanded blastocyst stages of development and cultured in vitro to the expanded blastocyst stage. Their capacity for postimplantation development was assessed after transfer to pseudopregnant foster mice. Embryos bisected at blastocyst stages had a higher survival rate in vitro than those bisected at the morula stage. Half-embryos had approximately half the number of cells at the blastocyst stage as control embryos, but the proportion of cells in the inner cell mass (ICM) was unaltered. The implantation rate of blastocysts derived from bisected embryos was only slightly lower than that of control embryos, but bisected embryos had a significantly reduced capacity to form fetuses. Histological analyses showed that failure to form a fetus is due to the absence of egg cylinder development, which correlates with the reduced number of cells in the ICM of bisected embryos. Postimplantation viability of half-embryos was significantly higher when blastocysts were transferred to Day-3 rather than Day-4 pseudopregnant recipients, presumably because of an increase in cell number in vivo prior to implantation. PMID- 2095590 TI - Cloning, cDNA analysis and prolactin-dependent expression of a marsupial alpha lactalbumin. AB - The gene for alpha-lactalbumin has been cloned from a tammar wallaby (Macropus eugenii) mammary gland cDNA library. Tammar alpha-lactalbumin has approximately 50 and 30% homology to the alpha-lactalbumins of eutherians at the levels of nucleotide and protein sequence respectively. Comparison of the inferred tammar polypeptide sequence with the sequence of the eutherian proteins reveals extensive divergence at almost all of the non-essential amino acid residues. However, the hydropathy plots of the tammar protein are almost identical to those of eutherian alpha-lactalbumins, suggesting that protein conformation is conserved. The tammar gene encodes a transcript of approximately 975 bases. Northern blot analysis of hormone-stimulated mammary gland explants shows that maximal induction of alpha-lactalbumin mRNA is dependent on prolactin and that expression is not modulated by other hormones that play a role in the initiation of lactation in eutherians. PMID- 2095591 TI - Structure and ovarian expression of the oxytocin gene in sheep. AB - In sheep, the oxytocin gene is highly up-regulated in the ovarian corpus luteum as well as in the hypothalamus. This expression is already elevated on Day 2 of the oestrous cycle, representing 1% of all transcripts in this tissue, and it declines thereafter to low levels after Day 6 of the cycle. In order to study the mechanisms involved in luteal oxytocin gene expression, we have cloned and sequenced the oxytocin gene from the sheep. This gene is closely homologous to other known mammalian oxytocin genes, especially the bovine one, and comparison of the gene promoter regions highlights several blocks of putative control elements. PMID- 2095592 TI - Effects of progesterone antagonists RU486 and ZK98734 on embryo transport, development and implantation in laboratory mice. AB - Two progesterone antagonists blocked the actions of progesterone on uterine mitosis and epithelial morphology, but had no oestrogenic, anti-oestrogenic, cytotoxic or gestagenic activities in the mouse uterus. They interrupted early pregnancy and were luteolytic. These actions were reversed by treatment with exogenous progestins, but not dexamethasone. Doses of antagonists which blocked pregnancy and were luteolytic induced premature entry of embryos into the uterus on Day 3 and loss from the tract by Day 4. With the more potent RU486, most embryos remaining in the tract on Day 4 were in the oviduct. This 'tube-locking' and accelerated loss were probably due to 'unopposed' actions of ovarian oestrogen. They were reversed by progestin treatment; this suggests that progesterone is essential for normal embryo transport. Doses of antagonists which prevented normal embryo transport and implantation had little effect on preimplantation embryo development. Small increases in numbers of abnormal embryos on Day 4 were not significant or dose dependent. Abnormalities were not correlated with location of embryos, nor prevented by progestin treatment which reversed antagonist effects on embryo transport and implantation. Hence, progesterone is apparently not essential for successful completion of preimplantation development of mouse embryos in vivo. PMID- 2095593 TI - Y or X--which determines sex? PMID- 2095594 TI - [The role of occlusion and articulation in craniomandibular dysfunction]. AB - Historically, occlusal interferences are considered to be a major etiologic factor of craniomandibular disorders. Recent evidence suggests however that occlusal and articular parameters only play a minor etiologic role, if any. This controversy will only be solved after studies investigating well-defined homogenous patient groups. Concerning treatment, appliance therapy has proven to be a valuable part of the conservative reversible treatment procedure which allows to manage the majority of craniomandibular patients. Irreversible procedures e.g. complex orthodontic or prosthetic therapy, occlusal equilibration or surgery are only necessary in select cases and apply to very strict guidelines. PMID- 2095595 TI - [Selective grinding in dental occlusion]. AB - Occlusion has often to be corrected by grinding, should it be in T. M. J. pain dysfunction cases, in periodontal cases or for the adjustment of prostheses. Indications and contra indications, clinical diagnosis, different means of marking interferences and the technique for grinding them in centric relation, protrusion and laterality are described. Emphasis is put on the necessity of completing the equilibration when it has been started because it is a general feeling that patients might become occlusion conscious and might be in danger of catching parafunctions. PMID- 2095596 TI - [Dental occlusion and orthodontics in children]. AB - Patients with malocclusions frequently function normally and retain their dentition without problems. Strong correlations between occlusal factors and mandibular dysfunction are still controversial. However, signs and symptoms of craniomandibular disorders appear to be prevalent in children as well as in adults. Almost no symptoms of dysfunction have been seen in children aged 3-6 year. Work in the developmental aspects of these disorders has to be done. Orthodontic therapy seems unable to prevent CMD or resolve these problems. Generally, it does not cause or predispose people to develop CMD. If painful symptoms arise during treatment, it may be necessary to modify active treatment. Occlusal equilibration must be carried out with very much caution. PMID- 2095597 TI - [Use of the facial arch: a case for a specialist?]. AB - Ideally, an articulator should reproduce exactly mandibular movements. Therefore, several parameters have to be registered and the first of them is the relationship between the dental arches and the hinge axis. This can be obtained with the face bow and enhances significantly the precision of the movement simulation. The use of a semi-adaptable articulator with an arbitrary hinge axis face bow allows to realise, through rather simple manipulations, nearly all prosthetic works with enough precision. Practitioners ought to use currently this equipment but it is not necessary in simple cases. Description is given of two semi-adaptable articulators offering various possibilities in their use: the CONDYLATOR and the SAM 2. PMID- 2095598 TI - [Integration of occlusal parameters in a combined prosthesis. Illustrated with the aid of a case report]. PMID- 2095599 TI - [Mounting a semi-adaptable articulator]. AB - This article briefly highlights the differences between mounting in articulator with the aid of an arbitrary face bow or an individually determined hinge-axis and discusses the importance of the registration of the central relation. A photo sequence illustrates the clinical use of a SAM face bow. PMID- 2095600 TI - [Occlusion, articulated and articulation]. AB - In this paper the so-called 'normal' or 'ideal' occlusal relationships are described in static centric as well as in dynamic, eccentric positions. However, difference is made between the different occlusal concepts. There is no real antagonism between the 'physiologic occlusal concept' in natural dentition and the 'therapeutic occlusal concept' on which the treatment should be based in restoring the occlusion. The different forms of occlusion and articulation found in the natural dentition are the expression of physiologic, biological variations. The rest position of the mandible is an unreliable reference point in occlusal rehabilitation. Moderate attrition in older patients should not be considered as pathologic and there is no indication for treatment in absence of functional pathology. PMID- 2095601 TI - Gamma delta T cells. PMID- 2095602 TI - A model for gamma delta T-cell development: rearranged gamma- and delta-chain genes incorporated into the germline of mice. PMID- 2095603 TI - Positive selection and extrathymic expansion of gamma delta T cells. PMID- 2095604 TI - Oral immunization with bacterial lysate against infection with Streptococcus pneumoniae in mice. AB - The protective effect of oral immunization against infection with Streptococcus pneumoniae was investigated in mice. Two bacterial lysates, one with an additional lysate of Candida albicans, were investigated. Intranasal inoculation of adult Balb-C mice with a S. pneumoniae type I strain resulted in a lethal infection, with deaths occurring from the 2nd until the 6th day after infection. Oral immunization resulted in a significant decrease in mortality rate (18-48% reduction). No significant difference in mortality rates was observed between the groups immunized with different lysates in the same concentrations. PMID- 2095605 TI - Alterations of the endoalveolar surfactant after surgery with extracorporeal circulation. AB - In 10 patients who required extracorporeal circulation (ECC) during surgery, we studied the damage induced by surgery to the pulmonary surfactant and the effectiveness of ambroxol in preventing changes in the phospholipid pool. There were 5 control patients and 5 patients who were given 1 g/day of ambroxol on the 4 days prior to and the 4 days after surgery. To follow changes in phospholipid concentrations, bronchoalveolar lavage (BAL) was performed before surgery and 24 h and 8 days after ECC. Phospholipids were assayed in the BAL liquid by two dimensional thin-layer chromatography. There were marked decreases in total phosphorus and quantitative alterations of individual phospholipid species in the surfactant of the control group, but not in the patients treated with ambroxol. PMID- 2095606 TI - Evaluation of a turbine flow meter (Ventilometer Mark 2) in the measurement of ventilation. AB - We have evaluated a turbine flow meter (Ventilometer Mark 2, PK Morgan, Kent, UK) at low flow rates and levels of ventilation which are likely to be encountered during exercise in patients with chronic respiratory disease. Pulsatile flows were generated from a volume-cycled mechanical ventilator, the flow wave-form was modified by damping to simulate a human breathing pattern. Comparative measurements of ventilation were made whilst varying tidal volume (VT) from 0.22 to 1.131 and respiratory rate (fR) from 10 to 35 min-1. At lower levels of ventilation the instrument tended to underread especially with increasing fR. The calibration factor must be adjusted to match the level of ventilation if the measurement errors are to be within 5%. PMID- 2095607 TI - Trace metal lung diseases: a new fatal case of hard metal pneumoconiosis. AB - Four subjects working in sharpening and grinding operations of hard metal tools were examined. Only 1 worker, a 37-year-old female exposed for 7 years to hard metal dusts, developed hard metal pneumoconiosis, which rapidly progressed to death. Cytology of the bronchoalveolar lavage (BAL) showed a high number of eosinophils, more than 30% of the cell population. Biopsy of the lung revealed interstitial fibrosis with hyperplasia of the pneumocytes of the second type and inflammatory cellular infiltration of the interstitium. High tungsten (W) and tantalum concentrations were determined in the admission BAL and in the biopsy 4 months later by neutron activation analysis while cobalt (Co) levels were near to normal values. The content of Co and W in blood and urine and particularly in pubic hair and toe nails of the patients was significantly higher than the normal values. This suggests that these biological specimens could be used as indicators of chronic exposure to hard metal dusts. PMID- 2095608 TI - Postmortem effects on the yield and composition of alveolar surfactant from rat lungs. AB - Isolation of alveolar surfactant from human cadaver lungs might be ineffective because of postmortem effects. We studied therefore in the rat the effect of autolysis on the yield and composition of alveolar surfactant at different intervals after death. The total amount of phospholipids in the lavage fluids decreased at 4 h postmortem and increased thereafter again. Increased amounts of proteins, significant deviations from the normal phospholipid composition of surfactant and decreased surface activity were already present from 2 h onwards. However, a normal alveolar surfactant can be obtained up to 16 h after death by using a sucrose gradient centrifugation procedure. With this procedure it is possible to isolate a surfactant with adequate surface activity from mildly, but not from severely autolytic rat lungs. PMID- 2095609 TI - Prognostic score for Pneumocystis carinii pneumonia. AB - Sixty episodes of Pneumocystis carinii pneumonia in 59 patients were evaluated for risk factors predicting fatal outcome within 14 days after bronchoscopy. We found significantly higher values for serum lactate dehydrogenase (p less than 0.001), alveolar-arterial oxygen difference (p less than 0.001) and percentage of bronchoalveolar lavage neutrophils (p less than 0.001) in patients dying within 14 days, but there was considerable overlap of these variables between the two groups. Using a score system combining the three parameters allowed however an excellent discrimination between the two groups. PMID- 2095610 TI - Comparative evaluation of the antitussive activity of butamirate citrate linctus versus clobutinol syrup. AB - In a double-blind randomized study 60 patients with either irritative cough due to seasonal respiratory disorders or chronic cough of any etiology were treated with either butamirate citrate linctus (Sinecod, Zyma) or with clobutinol syrup (Silomat, Boehringer, Ingelheim) for a period of 5 days at a dose regimen of 3 tablespoons daily. Efficacy was assessed based on the reduction of the severity as well as frequency of the cough and on the global opinion of the physician. Both groups showed highly significant improvements for the severity and frequency parameters (p less than 0.001), thus demonstrating the effectiveness of both treatments. No significant differences between groups were detected globally for the whole collective. For cough due to carcinomas (n = 14), however, a significantly better effect of butamirate on the frequency of cough (p = 0.026) was found which originated other significant differences in the global scores (p = 0.013) and in the physician's opinion (p = 0.026). Seven patients in both groups complained about side effects (mainly nausea and drowsiness). PMID- 2095611 TI - Effects of inspiratory and expiratory time and high mouth pressures on calculated DLCO by the single-breath procedure. Results with different methods to measure the effective breath-holding time. AB - We have studied the influence of several manoeuvres modifying inspiratory and expiratory flow, with and without an external obstruction, on measured single breath diffusing capacity (DLCO). By this method, we could evaluate the effects of increased inspiration or expiration time, independently of the influence of high (negative or positive) mouth pressures. Ten tests were performed in each of 11 trained normal subjects. The sequence of repeated manoeuvres was as follows: (1) basal; (2) inspiratory obstruction (IO); (3) expiratory obstruction (EO); (4) slow inspiration without obstruction (SI), and (5), slow expiration without obstruction (SE). A second, inverted sequence was then performed. The obstructive manoeuvres were forced by a unidirectional valve with a circular hole of 5 mm in diameter. Mouth pressures were registered. The slow flows were voluntarily controlled to be similar to the corresponding flows during the obstructive manoeuvre (approximately 15% of each vital capacity/second). Determinations of breath-holding time (tBH) were calculated by the methods of Jones-Meade, Ogilvie and the American Epidemiology Standardization Project (ESP), but using the same expiratory sample. We found that (DLCO) obtained with the three methods were statistically different (p less than 0.0001) from each other for all manoeuvres. Regarding the basal manoeuvre, there were statistical differences (p less than 0.01) with SI on the Jones-Meade, with IO on the ESP and with SI and IO on the Ogilvie timing methods. Between IO and SI, statistical differences (p less than 0.01) were observed in the three methods, but there was no statistical difference between SE and EO by any method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095613 TI - Tuberous sclerosis with pulmonary involvement. AB - Pulmonary involvement in tuberous sclerosis (pTS) is very rare and seems to be associated with a more benign course, compared to tuberous sclerosis without pulmonary manifestation (TS). Furthermore, pTS seems to be related to lymphangiomyomatosis (LAM). We present the case of a 33-year-old woman in whom the overlap of TS, pTS and LAM is demonstrated. Treatment with medroxyprogesterone was initiated, but without success. PMID- 2095612 TI - Sjogren's syndrome with bronchial gland involvement and multiple bullae. AB - A 52-year-old woman with Sjogren's syndrome presented with a dense lymphocytic infiltrate around the bronchial gland disclosed by a transbronchial lung biopsy specimen. Two and a half years after the initial evaluation, her pulmonary status had deteriorated and multiple bullae had developed at both lung bases. PMID- 2095614 TI - [Current medical genetics]. PMID- 2095615 TI - [Megaloblastic anemia in the elderly]. AB - From 1974 to 1984, the authors reviewed the clinical records of 20 elderly patients (10 male) at the Clinics Hospital of the School of Medicine of the University of Sao Paulo, who were admitted with megaloblastic anemia. Ages varied from 62 to 84 (mean 70.4 years). Clinical conditions was varied and usually severe, major systems affected being the hematologic, cardiocirculatory, neurologic, and digestive. Among hematological findings the most common were anemia with elevated cell volume, high neutrophil segmentation rate, leukopenia, thrombocytopenia and hemolysis. Pathological findings were present in all cases where endoscopy and gastric biopsy were performed. Clinical and hematological conditions were similar in patients with folic acid or vitamin B12 deficiency. 19 patients (90.0%) responded to therapy in an usually prompt and clear manner, however some neurological signs may persist. On the other hand, untreated patients may become seriously ill and even die due to cardiac, hemorrhagic, or infectious complications. PMID- 2095616 TI - [Usefulness of HLA-B27 in the diagnosis of ankylosing spondylitis: positive and negative predictive value and the probability ratio of diseases]. AB - The authors discuss the usefulness of the HLA-B27 test in the diagnosis of ankylosing spondylitis (AS). Sensitivity, Specificity, Predictive Value of a Negative Test, Predictive Value of a Positive Test, and Likelihood Ratio are defined and illustrated through the example involving HLA-B27 and AS. The HLA-B27 cannot be used as a screening test for the diagnosis of AS when evaluating an asymptomatic population, however the test is most useful in assisting the diagnosis of AS when used by physicians who understand the principles of probability. PMID- 2095617 TI - [Restandardization of thyroid uptake indices in patients with euthyroidism using 131I]. AB - The authors studied 454 patients in order to review the thyroid uptake pattern in Sao Paulo. They were submitted to clinical examination and hormone dosages (T3, T4 and TSH). Two hundred and fifty-four patients (55.9%) were excluded because they had hormonal dosages out of the normal range of substernal, diffuse and multinodular goiter, or were younger than 12. The 200 remaining patients (44.1%) were included in the euthyroidism group and the results were as follows: 2 hours thyroid uptake = 3 to 12%; 24 hour thyroid uptake = 8 to 32%. PMID- 2095618 TI - [Fine needle aspiration cytology in the diagnosis of head and neck tumors]. AB - The authors studied 166 head and neck tumors of patients admitted to the A.C. Camargo Hospital using the method of fine needle aspiration cytology (FNAC) in order to correlate these findings with pathohistological diagnoses. The correlation was possible in 81 cases: 3 cases were false negative and 1 was false positive. FNAC sensibility was 90.6%, specificity was 97.9%, and efficiency was 95%. PMID- 2095619 TI - [Relationship between hypertensive states and perinatal prognosis in abruptio placentae]. AB - Ninety-one occurrences of abruptio placentae were analyzed by the Department of Obstetrics of the Sao Paulo School of Medicine in Sao Paulo, Brazil during a ten year period, from 1979 to 1988. The purpose was to analyze perinatal prognosis and its relation to hypertensive states. The authors observed that arterial hypertension was present in 75% of the cases, most of which chronic arterial hypertension; they also observed that perinatal mortality increased in the presence of high arterial blood pressure. PMID- 2095620 TI - [Severe acute pancreatitis, laparotomies, and planned reoperation]. AB - Of 111 cases of acute pancreatitis studied, 13 (11.7%) patients had severe pancreatitis with infection and were submitted to planned reoperation or to open peritoneal drainage. Twelve patients were male, ages ranging from 20 to 56. The etiology was biliary in 4 patients, traumatic in 1 patient, and alcoholic in 8 patients. Early treatment included clinical support at the intensive care unit and surgical intervention was performed after the first week based on clinical signs and on ultrasound and CT scan findings. A total of 42 surgeries was performed (mean of 3.23 operations per patient). Mortality rate was 46% due to systemic complications and to multiple organ failure. PMID- 2095621 TI - [Neuropsychiatric disorders in systemic lupus erythematosus: a multidisciplinary review]. AB - Neuropsychiatric alterations appear in 14-75% of lupic patients. Verified in 59% of the patients, psychiatric changes are the most frequent. Psychic symptoms are primarily related to the disease and secondary to uremia, hypertension, infection, and corticosteroids. Manifestations were also seen as a reaction to this chronic disease, which are potentially severe and causing many limitations to the patients. The authors review the literature considering the multidisciplinary aspects of this disease related to its pathogenesis, clinical features, diagnosis, differential diagnosis, and treatment. PMID- 2095622 TI - [Heparins and antivitamins K]. PMID- 2095623 TI - [Iatrogenic pneumothorax caused by acupuncture]. AB - A 68 year-old white male patient with previous diagnosis of pulmonary emphysema was submitted to acupuncture. The needles were inserted into the precordial area and the patient immediately complained of worsening dyspnea. Four days later pneumothorax was detected by chest X-rays. A thoracic tube was inserted with total lung expansion. PMID- 2095624 TI - [Intraperitoneal pacinian neurofibroma (enlarged pacinian corpuscles)]. PMID- 2095625 TI - [A method for permanent fixation of eggs of enteroparasitic helminths]. AB - The results using the Hoyer method for examining eggs of helminths enteroparasites are presented. This method is particularly suited for teaching and on research purposes. Using this technique in fecal sample containing eggs of A. lumbricoides, T. trichiura, Uncinaria sp., Taenia sp., Diphyllobothrium sp., H. nana, H. diminuta and F. hepatica allowed the correct identification of then after 24 hours up to 180 days after the samples were obtained. PMID- 2095627 TI - [Histoplasmin and paracoccidioidin reactions in Serra de Pereiro. (Ceara State- Brazil)]. AB - Intradermal tests using histoplasmin and paracoccidioidin antigens were performed in 138 persons from Pereiro, Ceara, Brazil. The results were positive in 61.5% and 32.5% with histoplasmin and paracoccidioidin antigens respectively. These results suggest infection by H. capsulatum and P. brasiliensis in the people living in the studied area. New studies are necessary to detect histoplasmosis and paracoccidioidomycosis as clinical diseases in that region. PMID- 2095626 TI - [Ecological aspects of American tegumentary leishmaniasis: 8. Evaluation of the enzootic activity of Leishmania (Viannia) braziliensis, in forest and peridomiciliary environments of the Ribeira Valley region, Sao Paulo State, Brazil]. AB - The evidence of mucocutaneous leishmaniasis transmission in the non-forest environment in the Ribeira Valley region, Sao Paulo, Brazil, has made this epidemiologic four years' study possible, viewing the enzootic activity of L. (V.) braziliensis. Furthermore, the natural infection in small mammals and the domestic dog population has been completed in collecting of phlebotomine sandflies in the forest and peridomiciliar environments. Positive test-results have only been found in resident dogs (Canis familiaris) with a rate of 5.6 and 2.4% for serological and parasitological test respectively. Among silvatic and synanthropic rodents collected, Oryzomys (Olygoryzomys) and Rattus rattus are pre eminent having both been collected in equal proportions, in peridomiciliar environment. The sandfly Lutzomyia intermedia has contributed only with 166 feminine specimens due to insecticide (DDT) application on and in the human and domestic habitations. From the general epidemiologic standpoint the fragile L. (V.) braziliensis cycle in the unforested areas as well as the canine and small mammals roles as a domiciliar infection source are discussed, and their potencial in the dispersion of this parasite in the researched area is analysed too. PMID- 2095628 TI - Comparative studies of Yersinia pestis outer membrane isolation techniques and their potential use in plaque epidemiology. AB - In the present study three techniques for obtaining outer membrane enriched fractions from Yersinia pestis were evaluated. The techniques analysed were: differential solubilization of the cytoplasmic membrane with Sarkosyl or Triton X 100, and centrifugation in sucrose density gradients. The sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of outer membrane isolated by the different methods resulted in similar protein patterns. The measurement of NADH dehydrogenase and succinate dehydrogenase (inner membrane enzymes) indicated that the outer membrane preparations obtained by the three methods were pure enough for analytical studies. In addition, preliminary evidences on the potential use of outer membrane proteins for the identification of geographic variants of Y. pestis wild isolates are presented. PMID- 2095629 TI - Differences between in vitro and in vivo obtained schistosomules. AB - The injection of cercariae of Schistosoma mansoni into the peritoneal cavity of naive mice induces cell adhesion to these larvae, and this adherence sharply decreases when the infecting larva changes to schistosomule. This procedure was used to detect differences between schistosomules obtained in vivo and in vitro. Reinoculation of schistosomules obtained in vivo into the peritoneal cavity of mice did not trigger cell adhesion. In contrast, adherent cells were found in 4 and 24-hour-in vitro schistosomules. Our data on schistosomules obtained in vitro indicate that more than 24 hours are needed for complete remotion of molecules involved in the phenomenon of cell adhesion. PMID- 2095630 TI - [Hidrobioid (Mollusca: Mesogastropoda) in Pedro Leopoldo and Lagoa Santa municipalities, MG, Brazil]. AB - Molluscs with shells very similar to Oncomelania nosophora were collected at Pedro Leopoldo and Lagoa Santa counties, MG, Brazil. They were identified, according to shell and soft part morphology, as Idiopyrgus souleyetianus. The others hidrobioids identified in Brazil are also listed. PMID- 2095631 TI - Hepatobiliary alterations in massive biliary ascariasis. Histopathological aspects of an autopsy case. AB - Hepatobiliary alterations found in an autopsy case of massive Biliary Ascariasis, are reported on histological grounds. Severe cholangitis was the main finding, but other changes were also detected, such as pyloric and intestinal metaplasia, hyperplasia of the epithelial lining, with intraductal papillomas and adenomatous proliferation. Remnants of the worm were observed tightly adhered to the epithelium, forming microscopic intrahepatic calculi. Mucopolysaccharides, especially acid, showed to be strongly positive on the luminal border, and in proliferated glands around the ducts. The authors discuss the similarity between such findings and Oriental Cholangio-hepatitis, and suggest that inflammation and the presence of the parasitic remnants are responsible for the hyperplastic and metaplastic changes, similarly with what occurs in chlonorchiasis, fascioliasis and schistosomiasis. PMID- 2095632 TI - Evaluation of enzyme-linked immunosorbent and alternative assays for detection of HIV antibodies using panels of Brazilian sera. AB - Sera from 472 Brazilian subjects, confirmed to be either positive or negative for HIV antibodies and comprising the total clinical spectrum of HIV infection, were utilized in the evaluation of six commercially available enzyme-linked immunosorbent assays (ELISA), as well as of four alternative assays, namely indirect immunofluorescence (IIF), passive hemagglutination (PHA), dot blot and Karpas AIDS cell test. The sensitivities ranged from 100% (Abbott and Roche ELISA) to 84.2% (PHA) and the specificities ranged from 99.3% (IIF) to 80.2% (PHA). The sensitivity and specificity of the PHA and the sensitivity of the Karpas cell test were significantly lower than those of the other tests. Although the IFF and dot blot had good sensitivities and specificities, the six ELISA were more attractive than those tests when other parameters such as ease of reading and duration of assay were considered. PMID- 2095633 TI - [Chronic perirenal hematoma following an overlooked kidney injury. Problems in diagnosis]. AB - Five cases of chronic perirenal hematoma are reported. Preoperative tests were performed to assess the malignant or benign nature of the lesions which were observed some time after the dramatic episode which marked their onset. The varying characteristics of the disease showed by different imaging techniques (urography, arteriography, US, CAT) are such that only surgery can remove all doubts in the majority of cases. PMID- 2095634 TI - [Evaluation of the activity of the bladder detrusor muscle and analysis of bladder function in subjects with diabetes mellitus under insulin treatment]. AB - The present report concerns investigations of detrusor muscle adrenergic innervations in patients affected by bladder neuropathy secondary to diabetes without obstructive disturbances. Detrusor contractile activity evoked by NE is markedly reduced which can probably be attributed to receptor deficit. Urodynamic evaluation demonstrated a prevalence of sensory peripheral neuropathy than a motor conduction abnormality. In vitro study demonstrated that motor conduction abnormality of detrusor contractile activity is present early without bladder disturbances. Therefore early urodynamic measurements are necessary to evaluate bladder dysfunction and neuropathy in diabetic patients. PMID- 2095635 TI - [Intracavernous pharmacotherapy in men who have undergone cystectomy for neoplasia]. AB - Impotentia erigendi is a consequence of radical surgery such as cystectomy due to neoplasia. It is caused by damage to neurovascular structures, and in particular to the nerve fibres of the sacral plexus. Current therapies include the use of penile prostheses or drug therapy. The paper reports the Authors' personal experience of the use of intracavernous drug therapy in 24 patients cystectomised due to vesical carcinoma. Objectively valid results were obtained in 33% of patients. No complications were observed and the treatment represents a valid alternative to mechanical prosthesis. PMID- 2095636 TI - [Therapy of urinary tract infections. Clinical experience comparing norfloxacin to other quinolones]. AB - The paper examines to treatment of 40 cases of urinary infections and compares the efficacy of pipemidic acid, norfloxacin, cinoxacin and ofloxacin. All these compounds demonstrated a good level of therapeutic efficacy, both in terms of management and effectiveness; in particular, norfloxacin and ofloxacin were preferable to the other compounds since they caused fewer side-effects. PMID- 2095637 TI - [Functioning and non-functioning tumors of the adrenal gland. Presentation of 4 cases]. AB - The Authors describe their own experience of functioning and nonfunctioning tumors of the adrenal gland. In two cases the neoplasm was an adrenal adenoma, one causing a Cushing syndrome, the other clinically asymptomatic and associated with renal tuberculosis. In two patients the neoplasm was a clinically unsuspected pheochromocytoma and in one case it proved to be a malignant tumor. PMID- 2095639 TI - [Clear-cell carcinoma of the kidney in a patient with hairy-cell leukemia. Immunologic and epidemiologic considerations]. AB - The paper describes a case of light-cell carcinoma of the kidney in a patient affected by hairy-cell leukemia. The immunological status is assessed revealing a severe deficit of NK phenotype lymphocytes. Therapy with alpha interferon was proposed in order to stimulate killing and recruitment processes of new NK cells. PMID- 2095638 TI - [Leydigoma of the testis. Review of reported cases and presentation of 2 new cases]. PMID- 2095640 TI - [A case of lithiasis and stenosis of the urethra. Diagnostic and therapeutic problems]. AB - The association of urethral stenosis and stones is not frequent. The urethral stenosis, particularly common in males, recognizes, as predisposing causes, urethritis, IPB, perineal trauma, neurogenic bladder and, last, but not the least important, endoscopic treatments or repeated catheterism. The authors report a case of a 42 year old man who underwent, for urolithiasis, several endoscopic examinations, which became urethral-stenosis with stones within four years. With responsible and critical behaviour, etiology, the diagnostic procedures and the therapy (invasive or not) of the urethral-stenosis are examined and evaluated. Diagnosis must be based on a non painful approach (clinical, bacteriological, ultrasonography, uro-dynamic studies); the invasive procedures must be limited as much is possible. Whatever treatment is used, which may always give sequences or complications, a prolonged follow-up is mandatory to have an objective evaluation of the results. PMID- 2095642 TI - [Therapeutic problems in urology]. PMID- 2095641 TI - [Mass transfer of magnesium in hemodialysis]. AB - The rate of mass-transfer (MT) of magnesium during hemodialysis was studied in thirty-five patients with hypermagnesemia (Mg = 3.75 +/- 0.72 mg/dl) undergoing chronic hemodialysis. The aim of the study was to verify which is the best dialytical approach to remove the excess of magnesium. The concentration of Mg in the dialysate was of 1.82 mg/dl for all patients. MT was -0.51 +/- 0.36 g and no statistical difference was found between patients treated with cuprophan hollow fibers dialyzers, PAN and cuprophan plates. Mg MT is not correlated with dialysis duration (r = -0.23; p:ns), urea clearance (r = -0.08; p:ns), KT/V index (r = 0.03; p:ns), blood flow (r = -0.15; p:ns). In conclusion from our data, in agreement with other Authors, reduction of serum Mg levels is more convenient by obtained by a decrease in Mg concentration in the dialysate under 1.82 mg/dl, in order to increase the blood-dialysate concentration gradient. PMID- 2095643 TI - [Inhibition of rat heart and kidney allograft rejection by photochemical treatment of the recipient]. AB - After temporary posttransplant PUVA treatment of graft recipients the survival time of rat heart and kidney allografts was significantly prolonged. In the semiallogeneic F1 model all kidney transplant recipients survived without rejection signs. The mechanism of action should be cleared especially the role of cis-urocanic acid and the introduction of the method into clinical organ transplantation is discussed. PMID- 2095644 TI - [Allogenic cartilage transplantation--immunohistochemical investigations on the antigenicity of the perichondrium]. AB - Perichondrium of human nasal, tracheal, costal and conchal cartilage was analysed by an immunohistological staining technique using monoclonal antibodies against different class II antigens. Our morphological study shows clearly the presence of class II antigens on the perichondrium of nasal, tracheal and conchal cartilage. Therefore the transplantation of cartilage allograft free of perichondrium may be preferred. PMID- 2095646 TI - [Animal experiments for testing the behavior of compacted bone sections using compression osteosynthesis after hyperthermic denaturation]. AB - In animal experiments on domestic pigs the behaviour of hyperthermically denatured autogenic compact bone grafts after orthotopic replantation was investigated histologically. It was shown that the inductive osteogenetic celldifferentiation of the lair tissue caused by the autogenetic osteoimplantation depends on the location relationship of the replanted bone grafts to the lair bone tissue. This differentiation had progressed after 14 and 21 days further in the upper indifference area than in the contact and fissure healing area. PMID- 2095645 TI - [Biocompatibility of various surgical drainage materials in the cytotoxicity and implantation test]. AB - The biocompatibility of 10 materials used for surgical drainage was evaluated in a cytotoxicity test and in rat subcutaneous tissue implantation test. All rubber materials and silikolatex were found to be cytotoxic. There was no correspondence of the results of the cytotoxicity test with those of the implantation test. Therefore various procedures for biocompatibility-testing should be used. PMID- 2095647 TI - [Immunoglobulin therapy of postoperative sepsis]. AB - 35 patients with septic postoperative complications entered a prospectively randomized study. The clinical state of these patients was daily determined using the sepsis score described by Elebute and Stoner. Endotoxin and antithrombin III were measured in the plasma using the limulus-amoebocyte-lysat test for endotoxin determination. The septic patients were treated with an immunoglobulin preparation (Pentaglobin) administered by the intravenous route. This preparation is enriched in IgM and IgA. Due to the immunoglobulin therapy the endotoxin titres decreased; simultaneously a reduction of mortality and shortening of time of hospitalization and of mechanical ventilation were observed. PMID- 2095648 TI - [Connection of immune status, nutritional status and postoperative complications in patients after surgery for organic esophageal stricture]. AB - The postoperative complications were analysed in 64 patients after operation for stricture of the esophagus. The underfeeding in consequence of the esophagus stricture reduced the cellular immune functions and increased the operative risk. The comparison of the feeding and immune parameters of patients with benign and malign strictures of the esophagus showed that the poor immune reactivity is caused by the underfeeding first of all and not by the immune depression due the tumor. PMID- 2095649 TI - [Effect of various fixation agents on ultrasound damping in normal and pathological testicular tissues]. AB - In normal and pathological testicular tissue the influence of various fixing agents (Formalin solution, Bouins solution, Hellys solution, Carnoys solution) concerning the acoustical properties of testicular tissue was examined. By means of an ultrasound spectroscopic measurement technique the ultrasound damping was registered by calculation of the ultrasound damping coefficient alpha. The results show that the most lower alpha values were obtained by fixation with formalin solution as well in normal as in altered testicular tissue. The results of fixation according to Helly, Carnoy and Bouin did show markedly differences. Therefore, the fixation of testicular tissue using formalin solution is the best way for experimental examinations of the ultrasound damping behaviour. PMID- 2095650 TI - [Influence of examining temperature on the ultrasound attenuation in testicular tissue]. AB - By means of an ultrasound spectroscopic measurement technique the influence of examining temperature on the ultrasound attenuation was experimentally investigated on formalin-fixed normal and altered testicular tissue. In the examined tissue specimens a temperature-dependent change of ultrasound attenuation (alpha on 6 MHz) was found in the temperature area between 10 and 50 degrees C. In the altered testicular tissue a higher damping decline could be observed. On the measuring points the specimens were examined by light microscopy. PMID- 2095651 TI - [Experimental investigations on the effect of the transducer-specimen distance on the ultrasound attenuation of formalin-fixed testicular tissue]. AB - Additional information on the tissue structure are possible by estimation of sound physical parameters in comparison with normal B-scan ultrasonography, especially the frequency-dependent ultrasound attenuation. The ultrasound attenuation measurements were made on histochemical normal and pathological testicular tissue with changing transducer-specimen distance. No markedly difference in damaging behaviour was found between normal and pathological testicular tissue at different distances. PMID- 2095652 TI - [Behavior of alkaline serum phosphatase (AP) and its bone isoenzyme in healing of the osteotomized tibia in rabbits--an animal experimental study]. AB - The effectiveness of the electrical stimulation on the healing of an osteotomy was proved by determining the total alkaline phosphatase (AP) in the serum and its bone isoenzyme in rabbits. A non-stimulated animal group served as control. The changes appeared more distinctly by interference stimulation than by stimulation with bipolar rectangle impulses. PMID- 2095653 TI - [Arterio-coronary venous difference in lactate concentration--a new objective and topical available parameter for the estimation of the energy metabolism status of the heart]. AB - Cardiosurgical operations were tested experimentally by means of a perioperative metabolic-energetic monitoring and by the conventional method of the hemodynamic monitoring (Swan-Ganz-catheter). By that could be shown that a perioperative monitoring by means of the arterio-coronary venous difference of the lactate level is possible. Intraoperative information about the topical metabolic energetic condition of the myocardium is to receive as the decisive advantage of this method. An improvement of the therapy results is possible in that way by an optimum of the treatment. A metabolic recovery of the heart during the operation was substantial more favourable for the postoperative myocardial restitution than an early application of catecholamins. This method for perioperative observation should be used specially in risk operations (NYHA-stadium III-IV, reoperations, etc.). PMID- 2095654 TI - [Effect of neurosurgical interventions on serum levels of the essential trace elements zinc and copper--a perioperative study]. AB - The serum-concentrations of the trace-elements zinc and copper were assessed before and after neurosurgical interventions in 60 patients. On the day of surgery the mean values of zinc and copper showed a significant decrease, but had reached their preoperative level one week later. While a influence of dexamethasone on the serum zinc levels could not be deducted, the serum copper concentrations seem to be influenced by dexamethasone. These changes seem to be connected with the activation of the hypothalamus-pituitary-adrenal axis during surgical stress. PMID- 2095655 TI - [Permanent tracheostomy in rats]. AB - For bronchoalveolar lavages (BAL) after lung transplantation in the rat two different tubes for creation of a permanent tracheostoma were devised and tested. Typ I was of plastic material and required closure of the trachea oral of the tube thus excluding the upper respiratory tract for breathing. All these animals deprived of their sense of smell and direction died within 50 hours despite optimal husbandry. Typ II was a T-shaped metall tube allowing normal nasal breathing. This tube was well tolerated by the animals and facilitated repeated BAL. BAL on day 3 following tracheotomy with 5% lymphocytes, 2% polymorphonuclear leukocytes and 95% alveolar macrophages was considered to be normal when compared with human findings. An increase in polymorphonuclear leucocytes and epithelial cells together with bacteria on day 6 was believed to be due to tracheobronchitis. This assumption was supported by the fact, that both cell types and the number of bacteria significantly decreased 3 days later. A steady increase of lymphocytes seems to be associated with repeated BAL. PMID- 2095656 TI - [Hot air coagulator for the treatment of bleeding of parenchymal organs]. AB - Experiences are described about the hemostasis in parenchymatous organs by means of a self-constructed hot air coagulator. Bleedings in liver, spleen, and kidney were caused experimentally in 15 dogs. A certain control of hemorrhage were carried out by hot air. The own hot air coagulator was superior to other coagulators by the little weight and the fast and noiseless working. PMID- 2095657 TI - [The development of theories of avoidance learning and its application to behavioral pharmacology]. AB - How the development of theories changed the definition of avoidance behavior was discussed. Three major theories of avoidance learning; the two-process theory, the species-specific defense reactions hypothesis, and the cognitive expectancy theory were reviewed. Very few innovations were brought to the experimental apparatuses and procedures by which these theories were tested. The paradigms have been applied without any theoretical considerations. Therefore, I claim here that the modification or renewal of experimental paradigms will be needed to make suitable animal models for psychopharmacology. PMID- 2095658 TI - [Microdialysis: a method to construct a microdialysis probe and its applications]. AB - This paper describes a removable microdialysis probe constructed inexpensively and easily from a commercially available iv catheter placement unit and flexible fused silica tubing. The probe is characterized in in vitro recovery tests. As an example of its applications, experimental results measuring extracellular dopamine concentrations in the nucleus accumbens of rats during intracranial self stimulation behavior are reported. PMID- 2095659 TI - [Functional organization of the rat somatosensory cortex and its plasticity]. PMID- 2095660 TI - [Has the frequency of renal cell carcinoma increased in autopsies]. AB - Earlier analyses of autopsy material may show no or only slight increase of renal cancer. However, in Scotland and Connecticut a significantly rise of male renal cell carcinoma was found. Since 1966 in the autopsy material of the area Rugen- Stralsund the frequency of female renal cell cancer have been significantly increased. In these cases the simultaneous occurrence of diabetes mellitus and earlier cholecystectomy is slightly elevated. PMID- 2095661 TI - [Corpus cavernosum injection treatment of erectile impotence]. AB - Through the use of vasoactive substances an improvement of diagnosis and treatment of men suffering from erectile dysfunction was obtained. From June 1988 to December 1989 in 108 patients an intracavernous injection therapy trial was performed. The response rate 85% and in 69% of the patients an organic disorders was found. Five percent of the patients have had a prolonged erection after intracavernous papaverine phentolamine injection. All cases have been treated successfully by local use of the sympaticomimetics Noradrenaline. The use of vasoactive substances is the method of choice in diagnosis and treatment of erectile dysfunction. PMID- 2095662 TI - [Comment on the contribution, "Agenesis of the inferior vena cava"]. PMID- 2095663 TI - [Clinical and morphologic factors for assessment of risk of progression of chronic glomerulonephritis]. AB - In 182 patients suffering from bioptical-proved and functional adapted chronic glomerulonephritis the relation between clinical course, morphological type and progression of disease has been evaluated. The presented results show a significant relation between the clinical course of chronic glomerulonephritis and the progression trend of this disease. The early finding of sclerotic changes may follow a benign course of the disease. PMID- 2095664 TI - [Serotonin uptake of thrombocytes as a measure of thrombogenicity of adsorbents]. AB - Serotonin intake into platelets is an active carrier-mediated metabolic achievement. This uptake may be reduced by unphysiological irritation on platelet membrane. Therefore, it is suitable for judgement of thrombogenicity of biomaterials. The 14C serotonin intake after blood contact with various adsorbents was investigated: Haemoresin (GDR), Adsorba 300 C (USSR) and syrendivinylbenzencopolymer FK 1621 (GDR). Only by the latter the serotonin intake was significantly reduced with 72.5 +/- 2.0% in comparison with siliconized glas (84.0 +/- 1.5%; p less than 0.001). Precision and analytical sensitivity of the method are high with a variation coefficient of 1.5 to 3.5%. PMID- 2095665 TI - [Effect of serum and ultrafiltrate (less than 50 k DA) of normal serum and uremic serum from chronic hemodialysis children on lipid peroxidation and vitality of fetal rat hepatocytes in vitro]. AB - The influence of ultrafiltrate with a molecular exclusion border of less than 50 kDa of hemodialyzed children on viability and lipid peroxidation (LPO) of hepatocytes was investigated in the model of fetal rat hepatocytes. Viability of cells was estimated by trybanblue test and malondialdehyde equivalents (MDA) were estimated by thiobarbiturate method as parameters of LPO. Ultrafiltrate of uremic patients may lead to a concentration-dependent loss of viability and simultaneous reduction of MDA formation of hepatocytes after incubation of 120 min. Uremic serum may reduce the viability, but not the MDA formation of hepatocytes opposite to uremic ultrafiltrate (p less than 0.01). In uremic serum high molecular substances (greater than 50 kDa) may show a cytotoxic effect, but on the other side low and high molecular substances may increase the antioxidative capacity in comparison with serum of healthy volunteers. PMID- 2095666 TI - [Meeting report. Second European Symposium on stone disease, Basel, 22 to 24 March 1990]. PMID- 2095667 TI - [Snoring: an epidemiological study on 1146 adult subjects]. AB - An epidemiological survey of the prevalence of snoring was performed on 1146 adults consecutively observed in the offices of several practitioners. A reliable, previously assessed snoring questionnaire was given to all patients. Snoring was found as a common sign as 31% of the subjects referred to this symptom. However, the prevalence of every-night snoring was 13.5-17.7%. Snoring was an age-related phenomena: its prevalence raised with age. Males more frequently proved to be heavy snorers although no great difference was found between sexes in the later decades of life. PMID- 2095668 TI - [Test-retest reliability of anamnestic data on chronic obstructive apnea]. AB - A questionnaire concerning problems inherent to ronchopathy was evaluated in order to assess its test-retest reliability and the interobserver variability of the items. The results indicate the existence of three orders of variables. The first (class A) was characterized by good intra- and inter- observer reliability. It included all interval variables (i.e. weight, height, arterial pressure) and most ordinal variables (i.e. grading of snoring, excessive daytime somnolence, morning headache, smoking, etc.). The second (class B) was characterized by good intra-observer and poor inter-observer reliability. It included snoring onset time and morning somnolence. The third class (class C) was characterized by both poor intra- and inter-observer reliability. It included sleep apnea. For large epidemiological survey purposes the authors suggest that only class A variables be used. PMID- 2095669 TI - [Use of SPECT in the diagnosis of vertigo syndromes of vascular nature]. AB - Dizziness is doubtlessly one of the most common symptoms to arise in ischemia of the brainstem. In such cases the circulatory deficit can not only cause a direct lesion of the vestibular structures but it may also block the compensatory process. There are, however, significant difficulties in establishing whether such dizziness can be attributed to a brainstem insufficiency (BI). In fact, both CAT and NMR provide data only in the case of permanent CNS tissue lesions and tests such as the Doppler examination of neck blood vessels are unable to establish the true state of cerebral blood flow. In order to obtain semi quantitative data regarding cerebral blood flow 99mTc-HMPAO-S.P.E.T. (Single Photon Emission Tomography) was used in 18 patients suffering from dizziness and for whom there was strong indication that the underlying cause could be vascular. There was a discrepancy between the Doppler and S.P.E.T. findings in 50% of the cases. CAT, however, proved negative in all but one of the cases. These data indicate that Doppler testing of the neck blood vessels can provide useful information regarding the status of the cerebral-afferent vessels but that these cannot be correlated to the level of cerebral blood flow. On the other hand, with S.P.E.T., in 15 of the 18 patients, it proved possible to identify significant alterations in cerebral blood flow in the absence of any permanent tissue lesions as those revealed by CAT and NMR. In the light of the present results cerebral S.P.E.T. appears to be a highly valid tool when, faced with dizziness for which a vascular origin is suspected, one must evaluate cerebral prognosis and therapy. PMID- 2095670 TI - [Evoked auditory potentials in neonatal hyperbilirubinemia]. AB - Neonatal hyperbilirubinemia (greater than 20 mg%) is an audiological risk factor. In order to check early detection of bilirubin-induced neurological damage in the brainstem, 19 newborns were enrolled in the present study. The criteria was a bilirubin level ranging from 12 to 20 mg%. A likely mechanism for bilirubin intoxication may be the slowing and desynchronization of acoustic stimuli in the brainstem. Auditory brainstem responses were performed using non filtered clicks at 100 dB SPL (peak equivalent). Absolute and interpeak latencies of waves I and V were measured and correlated to bilirubinemia upon acoustic stimulation and maximal bilirubinemia observed during neonatal observation. Significant correlations were noted between bilirubinemia and V or V-I latencies. No significant correlation was observed between bilirubinemia and wave I latencies. Similar results were obtained in a restricted group of term neonates with hyperbilirubinemia. It is, thus, concluded that hyperbilirubinemia affects the upper auditory pathways. PMID- 2095671 TI - [Spontaneous reparation of post-traumatic tympanic perforation: an experimental study in rats]. AB - In most patients tympanic membrane perforation spontaneously repairs itself. Nonetheless, in several cases the perforation persists due either to traumatic or phlogistic damage. Although the membrane perforation healing process has been under study for over a century there are still two contrasting theories. One of these theories asserts that repair takes place through the growth of granulation tissue while the other believes that epithelial migration is at the basis of healing. In the present study an experimental animal model (rat) was used in order to assess the staging of the natural evolution of post-traumatic membrane perforation and to characterize, from a morphological and sub-microscopic point of view, the cellular population and microstructural aspects of the extracellular matrix. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were employed to evaluate the progress in tympanic membrane healing and to make a comparison with the most recent theories. Eighteen Sprague-Dawley rats weighing 230-260 gr of the same age (10 weeks) were used in the study. The animals were anesthetized by intraperitoneal injections of Na-pentobarbital (NembutalR) (45 mg/Kg) and, under operating microscope, bilateral perforation of the upper rear quadrant of the pars tensa was performed with a myringotomy lancet. The animals were subjected to periodic follow-ups over next 30 days. Three animals were sacrificed during each control and the tympanic membrane was removed for TEM and SEM study. On the basis of the present study the following conclusions can be drawn: a) primary healing of the lesion is through granulation tissue; b) the healed T.M. is composed of three normal layers as is the normal T.M.; c) the presence of fibroblasts in the intermediate neoformed fibrous layer leads one to conclude that its extracellular matrix is produced and organized "in situ"; d) the neoformed lamina propria has a disorganized, fibrous structure. PMID- 2095672 TI - [Clinical classification of laryngeal carcinoma. Critique of existing classifications and proposal of a new working classification]. AB - Clinical classification of cancer of the larynx is an intriguing problem that has not been yet solved by the several proposals followed on during thirty years. The main disagreement deals with their aims that have become strictly prognostic, with no egard for therapeutic indications in individual cases. Apart from this aspect, the prognostic factors taken into account even by the last drawing (TNM UICC 1987) seem too rough to allow a correct statistical comparison among the different therapeutic modalities that can be applied to each clinical situation. This lack becomes exceedingly relevant when controlled therapeutic trials are to be planned, comparing radiotherapy with the various types of surgical procedure. A careful critical review of the successive clinical classifications (UICC, AJC) is made and a new descriptive working classification (CLM) is proposed. It aims first of all at a more rational organization of the main prognostic factors to be considered for all locations and stages, with no radical distortion of the last TNM UICC staging system, some details excepted. Afterwards each stage is subdivided into substages according to the presence or absence of those prognostic factors of known influence on applicability and outcome of all various therapeutic modalities, with particular emphasis to some pending problems. CLM classification makes it possible to set up homogeneous groups of cases on which every type of prospective or retrospective comparison of different treatments can be made. Advantages of the CLM working classification are: no need for further modification; possibility of giving information, after appropriate check, about therapeutic indications; possibility of moving quickly and simply subcategories of cases with similar prognosis from CLM to TNM. PMID- 2095673 TI - [Electrophysiologic monitoring of the facial nerve during otoneurosurgery]. AB - The use of intraoperative facial electromyography (EMG) during otoneurosurgery facilitates anatomic and functional preservation of the VII nerve recording neural activation evoked both mechanically and electrically. The present work presents a personal experience involving the use of this technique in 27 cases of otoneurosurgery (16 neuromas of the acoustic nerve, 4 tympano-jugular paragangliomas, 5 VII nerve decompressions, 1 vestibular neurectomy, and 1 VII nerve neuroma monitored intraoperatively with Nicolet Nerve Integrity Monitor-1 (NIM-2). The latter is a highly sensitive instrument for intraoperative electromyographic recording. It is equipped with a system for electric stimulation, a display and a speaker for the EMG signal and acoustic alarm. During monitoring basically 3 types of EMG responses can be recorded: "burst", "train" and "pulse". In the present work the various EMG patterns are analyzed in detail as well as the relationship between their emergence and the type of surgical procedure performed. Intraoperative interpretation of the EMG activity makes possible more precise, intricate surgical maneuvers. It is felt that intraoperative monitoring has made it possible to preserve the anatomy and functionality of the facial nerve more frequently than is possible with other unmonitored cases. This becomes most evident when evaluating the long-term results. PMID- 2095675 TI - [Francesco Pocchiari and Superior Institute of Health]. PMID- 2095676 TI - [The Italy-USA program for tumor therapy]. PMID- 2095677 TI - [The AIDS project]. PMID- 2095674 TI - [Intracranial post-traumatic aneurysm of the internal carotid artery as cause of epistaxis: considerations on 2 cases]. AB - Aneurysm of the internal carotid artery is rarely mentioned as a cause of epistaxis. This condition is quite rare but it is important to consider aneurysms in the etiology of epistaxis because of their high mortality rate and since they require management quite different from that of epistaxis of other origins. After arteriosclerosis the most frequent cause of an aneurysm of the internal carotid artery is a closed or penetrating craniofacial trauma injuring the artery. This leads to subsequent aneurysmal dilation of the cavernous and petrous portions of the artery itself. Aneurysms of the cavernous portion of the artery are more frequent. In this location the aneurysm has a close anatomical relationship with the sphenoid sinus as well as the nasal fossae. In the present paper two cases of traumatic intracavernous carotid aneurysms presenting epistaxis are described. In the first case, reported 25 years ago, the diagnosis was made on an autoptic table in young man who died after two severe episodes of massive nasal hemorrhage. The second case involved a 17-year-old man with a severe epistaxis reported one month after a close craniofacial trauma. An intracranial carotid pathology was suspected because of the recurrence of nose-bleeding and the history of reduced visual activity. Therefore angiography was performed which revealed a small aneurysm of the intracavernous segment of the left internal carotid artery. Subsequently, an endovascular balloon embolization of the aneurysm was successful, preserving the parent artery. The importance of considering aneurysms in the differential diagnosis of massive epistaxis is emphasized. PMID- 2095678 TI - [The Information Service of the Instituto Superiore di Sanita]. PMID- 2095679 TI - Professor Francesco Pocchiari: a memoir. PMID- 2095680 TI - [The development of biotechnology in Italy: the insights and role of Domenico Marotta]. PMID- 2095681 TI - [Francesco Pocchiari: the man, his projects and accomplishments]. PMID- 2095682 TI - [In memory of Francesco Pocchiari]. PMID- 2095683 TI - [The scientific contribution of Francesco Pocchiari on the intermediate metabolism of glucose]. PMID- 2095684 TI - [December 1988: the last interview granted by Francesco Pocchiari. The enormous load of activities]. PMID- 2095685 TI - [The Istituto Superiore di Sanita and community biomedical research]. PMID- 2095686 TI - [From the Laboratorio di Chimica Terapeutica to the Progetto Farmaci: development of the pharmaceutical sector of the Istituto Superiore di Sanita]. PMID- 2095687 TI - [The National Inventory of Chemical Substances]. PMID- 2095688 TI - [Collaboration with the World Health Organization]. PMID- 2095689 TI - [The temporomandibular joint: anatomy, physiology, clinical review]. AB - The temporomandibular joint (TM joint) is a synovial joint with two condylar surfaces and an intra-articular cartilaginous disc. Its development has two origins. Its physiology is complex and intimately related to dental occlusion, which is why we talk about the temporomandibular and dental joint. Recent neurophysiological data allow a better approach to TM joint dysfunction. The lateral pterygoid muscle plays decisive role in the pathogenesis of TM joint dysfunction. PMID- 2095690 TI - [Surgical indications in temporomandibular joint dysfunction]. AB - There has been a renewed interest in diseases of the temporomandibular joint over recent years due to a better understanding of the pathophysiology improvement in surgical techniques and, most importantly, the development of multidisciplinary teams. The indication for surgery is still essentially clinical, although medical imaging is increasingly informative. Arthrotomography provides the most reliable information. However, continuing progress in magnetic resonance imaging will probably provide surgeons with the best indications in the future. In this article, the authors clearly distinguish between intra-articular disk and muscular diseases. The operative indications are discussed in relation to the clinical signs and the condition of the joint. PMID- 2095691 TI - [Dynamic MRI of temporomandibular joint: technique and application]. AB - Internal derangements or disk dysfunctions represent the most frequent pathology of the temporomandibular joint (TMJ). The radiological study of TMJ dysfunction was, for a long time, restricted to arthrography. More and more MR is used to study the TMJ, because MR, allows non-invasive visualisation of without the use of X-rays. Moreover a "dynamic" MR technique can be used to study disk movements during mouth opening. A lot of the internal derangement problems can be solved with this technique and arthrography can often be avoided. This dynamic MR technique is described and some cases are discussed. PMID- 2095692 TI - [Temporomandibular arthrography in 1990]. AB - After a description of the normal anatomy of the temporomandibular joint, the technique of examination is reported, including: a) opacification of both lower and upper joint spaces, b) standard films with mouth open and closed, in the sagittal and coronal planes, and c) systematic video-fluoroscopy. The indications are diagnostic and sometimes therapeutic (loosening of adhesions, reduction of meniscal displacement). The authors describe the arthrographic appearance of the various abnormalities observed in a series of more than 600 arthrograms. PMID- 2095693 TI - [Imaging of the temporomandibular joint]. AB - The recent advances in imaging of the temporomandibular joint (TMJ), especially the introduction of MR imaging and surface colls allowing precise visualization of superficial structures led us to reconsider the different techniques used in this very complex anatomical region, due to both its morphology and function. We also tried to determine their respective role, especially in the study of TMJ dysfunction syndromes, that represent the most frequent pathology of this region. Conventional radiography allows us to appreciate the overall amplitude of the joint movements, and to study bone abnormalities, but CT is much more precise in the study of cortical bone. In TMJ dysfunction, the joint itself is studied by either arthrography or MRI, but both techniques have their limitations and remain complementary in some aspects, which are detailed here, so that the choice between them depends on availability and therapeutic indications. PMID- 2095694 TI - [Denta Scan: programme of x-ray computed tomographic reconstruction used for the anatomical evaluation of the mandible and maxilla in preoperative assessment of dental implants]. AB - A radiological technique, using a new CT software program for the evaluation of alveolar process height and width is presented. Our experience with this technique is described. PMID- 2095695 TI - [Scanner in dental implantology]. AB - Computerized tomography allows a life-size morphological study and analysis of bony texture. The life-size documents obtained allow direct measurement on the radiographic coefficient. Computerized tomography guides coefficient. Computerized tomography guides implant procedures: possibility of intra-osseous implantation, choice of implant (length and diameter), position of the implant, site of the implant in the cancellus bone or in contact with the cortex. PMID- 2095696 TI - [Radiology and the tooth]. AB - Radiological examination of the tooth and its appendages (periodontium) was poorly defined for a long time. It is based on a panoramic film, constituting a real scout film often completed by occlusive and intraoral films. The long-cone retro-alveolar assessment allows exact evaluation of dental and periodontal disease and determination of its nature (periodontitis, complex active periodontitis, etc.). Apart from malignant diseases, the CT scan is virtually only used in implantology assessments. PMID- 2095697 TI - [Study of facial neuralgia]. AB - So-called idiopathic, essential trigeminal neuralgia is characterised by typical severe pain in the territory of the trigeminal nerve or one of its divisions. This entity remains a diagnosis of exclusion after investigation by computerized tomography and/or magnetic resonance imaging of the path of the trigeminal nerve and its branches, to exclude any neoplastic, inflammatory, infectious or vascular process. Nevertheless, surgical exploration and now medical imaging have revealed in a large number of cases of "idiopathic" essential trigeminal neuralgia, compression of the trigeminal nerve as it emerges from the brainstem by a vascular loop. PMID- 2095698 TI - [The facial bones. 60 questions and answers]. PMID- 2095699 TI - [The facial bones. 25 questions and answers]. PMID- 2095700 TI - Who's who on Mount Olympus: Bayesian solutions. AB - The computation of genetic risk in the highly endogamous family of an ancient greek god and goddess has been published in this journal as a pleasant puzzle (Ropartz, 1985 and appendix 1). This calculation was assumed to be direct and straightforward. However, a Bayesian computation taking in account most of the available information of the risk is possible. Four solutions of this quiz are given. These solutions illustrate the different strategies which can be followed when facing actual genetic problems. PMID- 2095701 TI - An expanded mouse-human hybrid cell panel for mapping human chromosome 16. AB - A mouse/human hybrid cell panel of human chromosome 16 has been extended to a total of 31 hybrids. These hybrids were derived from constitutional translocations and deletions ascertained during clinical cytogenetic studies. This panel of hybrids, together with four fragile sites, have the potential to divide chromosome 16 into 38 regions. Rapid detailed physical mapping of gene probes or anonymous DNA probes is possible using this hybrid panel. This hybrid cell panel also allows the physical mapping of other chromosomes with three breakpoints on chromosomes 1, 4, 11 and 13 and two on chromosomes 3, 10 and 18. PMID- 2095702 TI - Cytogenetic survey of sixty-one patients with preleukemic syndrome including myeloproliferative and myelodysplastic diseases. AB - The authors report on a cytogenetic survey of 61 patients with preleukemic syndrome (PLS). Of these, 41 had a myeloproliferative disease (MPD) and 20 a myelodysplastic syndrome (MDS). Clonal chromosome abnormalities appeared in 24 patients (39.3%) at disease onset. Such changes had a frequency of 26.8% in patients with MPD and 65% in those with MDS. The authors stress the usefulness of ethidium bromide high resolution techniques. They allow obtaining a larger number of metaphases and elongated chromosomes with higher banding resolution and could account for the frequent detection of chromosome changes in most groups of MDS patients in the present series. Moreover, they discuss the possible significance of some chromosome aberrations suggesting that patients with MPD may live longer than those with MDS because of their higher frequency of normal karyotypes. PMID- 2095703 TI - Reassessment of two apparent deletions of chromosome 16p to an ins(11;16) and a t(1;16) by chromosome painting. AB - Two apparent deletions of the short arm of chromosome 16 were studied by in situ hybridisation using biotinylated DNA from a chromosome 16 specific cosmid library (chromosome painting). One abnormality was delineated as a t(1;16)(p36;p12) and the other as a ins(11;16)(q13;p13.13p13.3). Apparently unbalanced de novo abnormalities detected by classical cytogenetic procedures should be interpreted with caution. In situ hybridization using DNA from chromosome specific libraries provides the appropriate technology to delineate such abnormalities. PMID- 2095704 TI - Cytogenetic analysis of a rare case of pediatric myxolipoma. AB - A cytogenetic analysis was performed in a rare case of big toe myxolipoma derived from a 3-year-old girl. We found in all metaphases analyzed a trisomy 19 and a tetrasomy 1q. The breakpoints of chromosomes 1 were localized in the region p12 p13. None of the chromosome abnormalities usually described in lipomas, were observed. PMID- 2095705 TI - Paracentric inversion 14. AB - A new familial case of paracentric inversion of chromosome 14 inv(14)(q24.1q32.1) ascertained by multiple abortions in a female carrier is presented. A review of the literature revealed 14 cases of paracentric inversion 14 recorded so far. According to the different breakpoints, two major groups of inversions of the long arm of chromosome 14 can be recognized. PMID- 2095706 TI - Mosaicism 45,X/46,X, t dic(Xp:Xp) in a girl with short stature. AB - An eight-year-old girl with marked short stature and no apparent stigmata of Turner syndrome was investigated. Clinical features include bilateral epicanthic folds, frontal bossing, prominent ears and normal intelligence. Ultrasound scanning revealed an apparently normal vagina, streak ovaries and no uterus. Bone age was normal. Karyotype analysis of peripheral blood lymphocytes showed mos 45,X/46,X tdic(Xp:Xp) in the ratio 66:34, respectively. In addition, three cells with different abnormal X chromosomes were present which possibly originated from a 46,XX clone. Replication of the duplicated X chromosome was consistently late and symmetrical. Buccal smear confirmation of the karyotype showed Barr body negative in 90% and large or bipartite in 10% of the cells. Karyotypes of the parents were normal. The clinical manifestations in cases of Xp deletion due to terminal rearrangement associated with or without a 45,X cell line are discussed. PMID- 2095707 TI - Penile enlargement in tetrasomy 18p: an additional feature? PMID- 2095708 TI - Reflections on small supernumerary (marker) chromosomes: could imprinting and isodisomy play a role in the phenotypic expression of hyperdiploidy? PMID- 2095709 TI - Relationship between gastric levels and antiulcerogenic activity of zinc. AB - The relationship between the absorption of an organic zinc salt, zinc acexamate, and its antiulcerogenic activity in a model of cold-restraint stress was studied. Serum and gastric levels of zinc, as well as its antiulcerogenic effect, were determined after oral or intravenous administration of zinc acexamate. Cytochemical and X-ray microanalysis techniques were also applied. In the rats subjected to cold-restraint stress, gastric levels of zinc correlated with the antiulcerogenic effect observed after administration of zinc acexamate. However, it was not possible to establish a relationship between serum levels and the pharmacologic effect of zinc. Our results in animals subjected to regular diet indicate that the antiulcerogenic effect exhibited by zinc compounds could be associated with the presence of zinc at different levels of gastric tissue. PMID- 2095710 TI - Mechanism of the vasodilating action of etozoline and its metabolites in guinea pig aorta. AB - The mechanism of the vasodilating action of the diuretic etozoline and of its metabolites d- and l-ozolinone was studied in isolated aortic strips from reserpine-treated guinea-pigs. Etozoline (10 microM to 1 mM) induced a concentration-dependent inhibition of the contraction evoked by increasing K+ concentrations (15 to 45 mM) in the perfusion medium. The inhibition was of a noncompetitive type. Etozoline also inhibited contractions induced by increasing Ca++ concentrations in the perfusion medium of aortic strips depolarized by 40 mM K+. The inhibition was concentration-dependent and of a noncompetitive type. Tetraethylammonium, at concentrations reported to increase Ca++ influx into smooth muscle cells by closing K+ channels, induced contractions of aortic strips that were highly sensitive to inhibition by etozoline. Analysis of the concentration-response curves for tetraethylammonium showed that the antagonism by etozoline was of a competitive type. The pA2 value for etozoline was 5.01 +/- 0.16. Also arterial spasm, obtained by prolonging the exposure of vascular strips to tetraethylammonium (30 min), was completely suppressed by etozoline. l- and d Ozolinone antagonized tetraethylammonium-induced contractions of aortic strips in an apparently competitive manner, but only at very high concentrations (1 and 3 mM, respectively). These results suggest that the vasodilating action of etozoline and of its metabolites is mediated by an inhibition of Ca++ influx into smooth muscle cells following a specific opening of K+ channels, but only etozoline may act through this mechanism at concentrations likely to be operative in vivo. PMID- 2095711 TI - Antiaggregatory activity of N-methyl- and N-isobutyl-1,2-diphenyl ethanolamines in rat platelets. AB - The ability of N-methyl-1,2-diphenyl ethanolamine (compound M), N-isobutyl-1,2 diphenyl ethanolamine (compound E), diltiazem and verapamil to inhibit in vitro ADP-induced platelet aggregation was examined in rat platelet-rich plasma. Pretreatment of the platelets with the compounds (0.1-3 mM) for 3 min at 37 degrees C, inhibited an ADP-induced aggregation in a concentration-dependent manner. The maximum percentage inhibitions induced by compounds M, E, diltiazem and verapamil were: 95.5 +/- 6.5, 98.4 +/- 7.5, 100 and 95.9 +/- 8.3% at concentrations of 3, 0.64, 0.96 and 0.4 mM, respectively (n = 8 - 12). The inhibitory dose 50 (ID50) values for compounds M, E, diltiazem and verapamil were 1.3 +/- 0.13, 0.29 +/- 0.01, 0.44 +/- 0.03 and 0.2 +/- 0.01 mM, respectively. The antiaggregatory effects were not antagonized by methylene blue (50-200 microM), but were completely antagonized (greater than 95%) by elevation of the Ca2+ level in the platelet-rich plasma by 0.2-0.7 mM. Co-administration of (-)propranolol (17 microM) with anyone of the compounds enhanced the antiaggregatory effects. The compounds (0.1-0.2 mM) enhanced the prostacyclin (0.01 nM)-induced antiaggregatory activity. The antiaggregatory effects of the compounds are likely to be due to an inhibition of influx of Ca2+ into the platelets. PMID- 2095713 TI - Influence of clonazepam on cortical epileptic afterdischarges in rats. AB - Epileptic afterdischarges were induced by low frequency stimulation of the sensorimotor cortex in rats with implanted electrodes. Stimulations were repeated 4 times with 10 min intervals. Stimulation was always accompanied by clonic jerkings of the forepaws and frequently also by rearing and falling of the animals even in cases when no afterdischarge followed. Afterdischarges formed by a spike-and-wave rhythm prevailed, but a transition to spikes superimposed on delta waves ("slow waves superimposed with spikes") as well as a "slow waves superimposed with spikes" type since the very beginning of afterdischarges were recorded. Spike-and-wave afterdischarges were accompanied by the same motor pattern as stimulation, i.e., by minimal clonic seizures. During the "slow waves superimposed with spikes" type of afterdischarges, the rats sat motionless; wet dog shakes appeared towards the end. Mixed types of afterdischarges were accompanied by both motor patterns closely correlated to the actual EEG pattern. Clonazepam (0.02, 0.1 or 1 mg/kg, i.p.) was injected 5 min after the first afterdischarge. The second afterdischarge was shortened in a dose-dependent manner. The shortening was also observed in the third and fourth afterdischarge. Both pure afterdischarge types (spike-and-wave and "slow waves superimposed with spikes") could be induced after clonazepam, whereas a mixed type of afterdischarges was abolished. Motor pattern accompanying stimulation was attenuated but never abolished by clonazepam, whereas the same clonic seizures during spike-and-wave afterdischarges were blocked by the highest dose of clonazepam. Dissociation of EEG and motor epileptic phenomena suggests a preferential action of clonazepam on generalization of epileptic activity. PMID- 2095712 TI - Programmed electrical stimulation in conscious dogs: electropharmacologic testing of amrinone. AB - In order to assess possible proarrhythmic properties of amrinone, serial programmed electrical stimulation was performed via several previously implanted electrodes in 12 conscious dogs during the late reperfusion phase following experimental myocardial infarction. In 6 dogs, programmed electrical stimulation was carried out before and following the administration of amrinone (Wincoram) at cumulative doses of 0.3, 1 and 3 mg/kg, i.v., while the rest served as control group and received matching volumes of saline. Amrinone decreased atrioventricular refractoriness but did not alter ventricular refractory periods in both normal and infarct zones. Amrinone (3 mg/kg) substantially enhanced intraventricular conduction. Induction of ventricular arrhythmias was attempted only at base line and following 3 mg/kg of amrinone. Inducibility was unaltered by amrinone. However, in two experiments we observed more severe forms of arrhythmia to be inducible following drug administration. The number of extrastimuli necessary for the induction of arrhythmias was decreased in two cases during treatment. In the control group, neither the nature of induced arrhythmias nor the number of extrastimuli was changed. We conclude that, in our model, amrinone exerts a moderate proarrhythmic effect when assessed by programmed electrical stimulation. This arrhythmogenic property may be due to an enhancement of intraventricular conduction. PMID- 2095714 TI - Dual effect of N-ethylmaleimide on agonist binding to bovine heart muscarinic receptors. AB - M2-Muscarinic acetylcholine receptors are identified in membrane preparations from calf heart by binding of [3H]quinuclidinyl benzilate. The alkylating reagent N-ethylmaleimide provokes two major changes in the competition binding characteristics of the agonist carbachol. At low temperature (0 degrees C), the reagent provokes a rightward shift and steepening of the competition curve in a GTP-like manner. This can be attributed to alkylation of the adenylate cyclase regulating component Gi. At 30 degrees C, the reagent also increases the affinity of the agonist for the receptor, presumably by direct alkylation of the receptor. PMID- 2095715 TI - Role of vasopressin in the blockade of the development of morphine tolerance by footshock and psychological stress. AB - To elucidate the underlying mechanism for the blockade of the development of morphine analgesic tolerance by footshock and psychological stress, we examined the role of arginine vasopressin in this process. Daily pretreatment with intracerebroventricular anti-arginine vasopressin antiserum suppressed the development of tolerance to morphine. The radioimmunoassayable arginine vasopressin content was decreased in the hypothalamus but not in other regions of mouse brain after exposure to an acute footshock or psychological stress. However, this change disappeared after 5 daily repeated treatments. Neither the development of morphine tolerance nor the brain levels of arginine vasopressin were affected by exposure to forced swimming stress. Neither a single nor 5 daily treatments with morphine induced any appreciable changes in arginine vasopressin content. However, morphine in combination with footshock, lowered this content as did, be it insignificantly, the combination of morphine and psychological stress after chronic treatment. Blockade by footshock and psychological stress of the tolerance development was dose-dependently abolished by daily pretreatment with intracerebroventricular arginine vasopressin. These findings suggest that arginine vasopressin plays a critical role in the blockade, by footshock and psychological stress, of the development of analgesic tolerance to morphine. PMID- 2095716 TI - Interactive effects of physostigmine and exercise on cholinesterase activity in red blood cells and tissues of rat. AB - Physostigmine is considered to be a potential pretreatment agent against organophosphate intoxication. This investigation elicits the effects of three intensities of acute exercise (50, 80 and 100% VO2max), administration of physostigmine (70 micrograms/kg, i.m.) and the combined effect of physostigmine and three intensities of acute exercise on cholinesterase activity in red blood cells and various tissues and endurance time in rats. The cholinesterase activity in red blood cells in exercised rats not exposed to physostigmine was significantly greater than that of unexercised controls (116, 112 and 108% of control, p less than 0.05, at 50, 80 and 100% VO2max, respectively) while in other tissues the cholinesterase activity in general decreased slightly. In unexercised rats given physostigmine, the cholinesterase activity ranges were 73 79, 66-68, 68-74, 67-81 and 57-61% of controls from 10-30 min in red blood cells, brain, heart, diaphragm and thigh muscle, respectively. In exercised rats exposed to physostigmine, the cholinesterase activity ranges were 54-51, 58-50, 77-73, 71 83 and 54-58% of controls from 10-30 min in red blood cells, brain, heart, diaphragm and thigh muscle, respectively. The results indicate that in control rats not given physostigmine, different intensities of acute exercise affect the cholinesterase enzyme to a moderate degree in red blood cells (p less than 0.05) and heart (p less than 0.05) without affecting brain, diaphragm and thigh muscle. Acute exercise modifies the effect of physostigmine significantly (p less than 0.01) by increasing the cholinesterase inhibition in red blood cells and brain without affecting other tissues. Exposure of rats to physostigmine (70 micrograms/kg, i.m.) increases the endurance time in rats (160-200 g weight), possibly due to peripheral vasodilatation and lowering of core temperature. PMID- 2095717 TI - Inotropic effects of tanghinin and acetyl-tanghinin on guinea-pig isolated papillary muscle. AB - Tanghinin and its acetylated derivative acetyl-tanghinin are two cardiotonic glycosides isolated from the seed of Tanghinia venenifera Poir. (Apocynaceae). In vitro, these two heterosides increase the contractile force of the guinea-pig papillary muscle. At an extracellular concentration of 1.2 mM of CaCl2, a concentration of 2.8 x 10(-6) M of tanghinin or acetyl-tanghinin increased muscle tension with 1.3 g and 1.5 g, respectively. In presence of an extracellular concentration of 2.4 mM of CaCl2, maximal effects--1.8 g for tanghinin and 2.2 g for acetyl-tanghinin--were obtained with a glycoside concentration of 2.4 x 10( 6) M. These maximal effects are sustained up to a concentration of 2.8 x 10(-6) M. At higher concentrations, the positive inotropic effect drops rapidly, followed by a rise in diastolic tension. PMID- 2095718 TI - Dichloroacetate attenuates myocardial acidosis and metabolic changes induced by partial occlusion of the coronary artery in dogs. AB - The present study was undertaken to examine whether dichloroacetate, which inhibits pyruvate dehydrogenase kinase and, therefore, increases the activity of pyruvate dehydrogenase, attenuates myocardial acidosis and metabolic changes induced by coronary occlusion. In dogs anesthetized with pentobarbital, the left anterior descending coronary artery was incompletely occluded to reduce the left anterior descending flow to a half to one third of the original flow (partial occlusion) to produce myocardial (regional) ischemia. Partial occlusion was continued for 90 min, and a bolus injection of saline or dichloroacetate was made intravenously 30 min after the onset of occlusion. Partial occlusion decreased myocardial pH significantly. An injection of dichloroacetate (150 mg/kg) increased myocardial pH that had been lowered by partial occlusion. Myocardial metabolites were measured in other dogs. Partial occlusion decreased the myocardial levels of adenosine triphosphate, creatine phosphate and energy charge potential, and increased that of lactate significantly, without affecting the myocardial levels of pyruvate and nonesterified fatty acids. Dichloroacetate attenuated the ischemia-induced changes in the myocardial levels of adenosine triphosphate, creatine phosphate, energy charge potential and lactate. These results indicate that dichloroacetate attenuates the myocardial acidosis and metabolic changes during coronary partial occlusion. PMID- 2095719 TI - [Cardiac Arrhythmia Suppression Trial: a disappointment?]. PMID- 2095720 TI - [Management of complicated myocardial infarction]. PMID- 2095722 TI - [Prevalence of arterial hypertension in Araraquara, Brazil]. AB - PURPOSE: To study the prevalence of high blood pressure (HBP) in Araraquara, Sao Paulo, Brazil. PATIENTS AND METHODS: Cross sectional study: cluster equiprobabilistic sampling of 1.8% of the urban population aged 15-74 years, old (1.199 adults: 533 men and 66 women). For each subject, an interview was performed, with the fulfilling of a questionnaire; measures of blood pressure (BP, systolic and 2nd diastolic) as well as height and weight were taken. Criteria of definition for HBP were those of WHO (greater than or equal to 160/95). RESULTS: Systolic BP (mean +/- standard error) for men 137.6 +/- 0.8 mmHg, and for women 130.9 +/- 1.0 mmHg. Second diastolic BP for men 88.5 +/- 0.5 mmHg and for women 84.0 +/- 0.6 mmHg. Prevalence of definite HBP: 32.0% of men and 25.3% women (28.3% both sexes). Prevalence of borderline HBP; 18.7% of men and 12.0% of women (14.8% for both sexes). The greater part of hypertensives (68.3%) was of mild cases (less than 105 mmHg the second diastolic BP). CONCLUSION: It is the highest prevalence of HBP in Brazil described till now, and, therefore, an important public health problem. PMID- 2095721 TI - [Lymphocytic myocarditis. Response to treatment with immunosuppressive drugs]. AB - PURPOSE: To evaluate immunosuppressive drugs on the treatment of myocarditis. PATIENTS AND METHODS: Right ventricular endomyocardial biopsy was performed in 102 patients with dilated cardiomyopathy. According to histopathologic aspect the patients were divided into two groups: I--with active lymphocytic myocarditis (ALM); II--without ALM: 51 patients. Ten patients from group I (Ib), with moderate or intense myocarditis were treated with prednisone and azathioprine during six months. RESULTS: After six months of observation, in group Ia (41 patients): 41 improved, 22% worsened and 12% died; in group Ib (10 patients): 60% improved, 10% worsened and 30% died; 51 patients in group II: 59% improved, 17% worsened and 10% died. Control biopsy on group Ib showed decrease of myocarditis in 62%. CONCLUSION: Immunosuppressive drugs do not always improve quality of life, or increase the survival, although in more than 50% of the cases it was possible to control inflammatory process. PMID- 2095723 TI - [Cineventriculography with radionuclides and intravenous dipyridamole in the prognostic evaluation after acute myocardial infarction]. AB - PURPOSE: To evaluate safety and usefulness of dipyridamole-radionuclide ventriculography (D-RVG), soon after acute myocardial infarction (MI), in the prediction of future cardiac events. Traditionally performed tests were also compared. PATIENTS AND METHODS: Forty-one patients (4 females) with recent MI underwent rest and dipyridamole (0.58 mg/kg of body weight) radionuclide ventriculography. The criteria for a positive test for ischemia was failure to increase left ventricular ejection fraction in 0.05 from baseline value. All patients had also coronary angiography and 36 patients underwent thallium-201 scintigraphy for comparison. The mean follow-up was 16 +/- 3 months. The following findings were considered future for events: cardiac death, reinfarction, significant angina or heart failure. RESULTS: During the follow-up 18 of the 20 patients who had cardiac events had shown positive dipyridamole-RVG, as opposed to 5 of 21 event-free patients (p less than 0.01). The ventriculographic criteria for a positive test and dipyridamole left ventricular ejection fraction were the strongest predictors of those medical events (p less than 0.01 and p less than 0.001). Among the 36 patients who had thallium-201 imaging, 16 subsequently had cardiac events and the scans were positive in 82% (p less than 0.01). Twelve (29%) patients experienced reactions during dipyridamole infusion although no fatal complications were noted. CONCLUSION: Dipyridamole-RVG is relatively safe and a sensitive predictor of future cardiac events soon after acute MI, although additional experience is required before this new technique should be routinely recommended as an alternative approach. PMID- 2095724 TI - [Ambulatory cardiologic care: comparison between patients from a referral hospital and from community health centers]. AB - PURPOSE--Comparison between patients from a cardiology referral center and those from community health facility. PATIENTS AND METHODS--564 (5.3%) of 10667 patients from the referral center--Instituto do Coracao (InCor) and 105 (58.6%) of 169 from community health facility--Centro de de Santo Amaro (CSSA), Sao Paulo. RESULTS--217 (35.8%) patients in InCor and 27 (25.5%) in CSSA were younger than 40 years of age. Female patients were more frequent: 316 (56%) in InCor and 70 (66.7%) in CSSA. In InCor, 317 (56.2%) patients lived in Sao Paulo City and in CSSA all the patients live in the surroundings. Forty-three percent of the patients sought for medical attention in InCor by themselves, without medical referral. The diagnosis of heart disease was established in 81% of the patients in InCor and in 92.5% of the patients in CSSA. Other tests (besides electrocardiogram and chest roentgenogram) were considered to be indicated in 35% of the patients from InCor. The diagnoses were: a) coronary heart disease in 92 (20.1%) cases (InCor) and in 8 (8.2%) cases (CSSA); b) valvular heart disease in 46 (10.1%) cases (InCor) and in 9 (9.2%) cases (CSSA); c) mitral valve prolapse in 31 (6.8%) cases (InCor) and in 7 (7.1%) cases (CSSA); d) congenital heart disease in 10 (2.2%) cases (InCor) and in 1 (1%) case (CSSA); e) systemic arterial hypertension in 161 (35.2%) cases (InCor) and in 55 (56.1%) cases (CSSA); f) Chagas' infection or Chagas' heart disease in 44 (9.6%) cases (InCor) and in 8 (8.2%) cases (CSSA); g) cardiac rhythm disorders in 38 (8.3%) cases (InCor) and in 8 (8.2% cases (CSSA); h) other diseases in 33 (7.2%) cases (InCor) and in 1 (1%) (CSSA); i) diseases of the aorta in 2 (0.4%) cases (InCor) and in 1 (1%) (CSSA). Medical treatment was recommended to 71.5% of the patients from the InCor and to 92.5% of the patients from CSSA. CONCLUSION--Our data suggest a degree of similarity between the groups of patients cared for in a cardiology referral center in our city in relation to a community health facility. These data may be useful in planning optimal use of referral hospitals facilities in our city. PMID- 2095725 TI - [Pacemaker with mechanical sensors. Accumulated experience in long-term follow up]. AB - PURPOSE: To evaluate the behavior of single chamber stimulation system, rate responsive with vibration sensing, taking into consideration the results of long term clinical follow-up. PATIENTS AND METHODS: From september 1986 to april 1989, 70 patients received pacemakers with vibration sensing. Sixty four patients (91.9%) implanted Activitrax I model and six (8.1%) Activitrax II. Thirty-one (44.3%) were men and the mean age was 51.2 years. Fifty-one patients (72.9%) had complete atrioventricular block, 11 (15.7%) sinus node dysfunction, one (1.4%) sinus node and atrioventricular disease, and one (1.4%) for therapeutic support of arrhythmia. The etiology of these dysfunctions were Chagas' disease in 31.4%, myocardiosclerosis in 35.7%, post-operative in 15.6%, post-av node fulguration in 5.8% and idiopathic in 11.5%. The group was submitted to clinic and electronic evaluation and laboratory examinations: echocardiogram, dynamic ECG, stress test and ergoespirometric test. The mean follow-up as 19.6 months. RESULTS: Clinic evaluations: decrease in congestive heart failure functional class in 86% of the patients. No recurrence of syncopes and no cardiac deaths. Echocardiogram: increase in ejection fraction in 42% of patients. Dynamic ECG: appropriate rate response in 94.3% of patients (good cronotropic response). Ergoespirometry: increase in oxygen consumption in 75% of studied cases, Electronic evaluation: absence of generator dysfunction; complications in 18% of cases, all corrected by reprogramation. CONCLUSION: The single chamber cardiac stimulation system with vibration sensing showed safety, efficacy and low rate of complications. PMID- 2095726 TI - [Acute pulmonary edema as an early manifestation of systemic lupus erythematosus]. AB - A 36 year-old male patient developed acute pulmonary edema due acute mitral insufficiency as early manifestation of systemic lupus erythematosus. The patient was treated with supportive measures, oxygen, furosemide, and isosorbide dinitrate. He was started on prednisone 60 mg daily 14 days later, after the diagnosis of lupus was established. The patients is asymptomatic with mitral systolic murmur 5 months after hospital discharge. PMID- 2095727 TI - [Fatal cardiac tamponade in systemic lupus erythematosus associated with vasculitis similar to polyarteritis nodosa]. AB - We report the case of a 21 year-old woman who developed systemic lupus erythematosus and fatal cardiac tamponade. Necropsy examination revealed cardiac tamponade as well as other findings of SLE and an unsuspected vasculitis similar to polyarteritis nodosa. PMID- 2095728 TI - [Cerebral malformation of the conceptus associated with maternal bacterial endocarditis and with aortic valve replacement during pregnancy]. AB - A twenty-three years old woman, without previous heart disease developed endocarditis with negative bloods cultures on the fourth month of her third pregnancy. Fever was controlled through antibiotics, however she developed cardiac insufficiency and was submitted to surgery for replacement of aortic valve with a bioprosthesis. The post operative period showed no problems and the patient was discharged on the forty second day after admission. On the thirty ninth week of pregnancy she gave cesarean birth, without complications. The newly born, apgar 5 (1 min.) and 7 (5 min) presented signs of neurological problems, characterized on the second month as a cerebral atrophy. Among various possible factors, the most likely would be cardiopulmonary bypass circulation as the cause of the neurological malformation. PMID- 2095729 TI - [Case 5/90 (Instituto do Coracao do Hospital das Clinicas--FMUSP]. PMID- 2095730 TI - [Mitral valve prolapse from the pathological point of view. Controversy about the "prolapse", "billowing", "floppy" and "flail" terms]. PMID- 2095731 TI - [Treatment of lymphocytic myocarditis: an unsolved problem]. PMID- 2095733 TI - [A new balloon catheter]. PMID- 2095732 TI - [Adaptable pacemakers]. PMID- 2095734 TI - Sporotrichoid cutaneous infection due to Mycobacterium chelonei in a renal transplant patient. AB - Atypical mycobacterial infections are becoming more common in dermatological practice due to increasing numbers of immunosuppressed patients. A case of cutaneous Mycobacterium chelonei infection with sporotrichoid spread in a renal transplant patient is described, and the current literature regarding clinical spectrum, histopathology and management of infection with this pathogen is reviewed. PMID- 2095735 TI - Massive cutaneous tumour of the scalp. Sebaceous carcinoma. PMID- 2095736 TI - Hair-Thread Tourniquet syndrome. PMID- 2095737 TI - Kawasaki syndrome. AB - Kawasaki syndrome is an acute multisystem inflammatory disease of young children first described by Tomasaku Kawasaki in the Japanese literature in 1967. He reported 50 cases of this entity under the rubric of acute febrile mucocutaneous lymph node syndrome, a designation that has more recently been superseded by the eponym Kawasaki syndrome. The disorder was further delineated and brought to the attention of American pediatricians in 1974. Recognition of the syndrome followed rapidly, and Melish, Hicks and Larson published the first series of American cases from Hawaii in 1976. Subsequently, Kawasaki syndrome has been documented worldwide. Although the disorder is known to be a systemic vasculitis with predilection for the coronary arteries, the etiology has remained obscure despite intense investigative efforts. PMID- 2095738 TI - Do all melanomas come from "moles"? A study of the histological association between melanocytic naevi and melanoma. AB - Histological examination of 1101 melanomas (990 superficial spreading and 111 nodular melanomas) from 1098 people revealed that 23.3% showed an associated melanocytic naevus. Of these, 56.5% were classified histologically as common acquired, 37.7% as dysplastic and 5.8% as congenital. Of the superficial spreading melanomas, 25.7% showed an associated naevus. By contrast, only 2.7% of nodular melanomas showed histological evidence of a coexisting naevus. When the superficial spreading melanomas were analysed by level, the presence of a naevus varied from 31.3% of level I melanomas to 21.3% of level IV melanomas. When thickness was measured, an associated naevus was found in 27.0% of superficial spreading melanomas less than 1.0 mm thick, and 14.8% of melanomas with a thickness of 1.0 mm or greater. These data suggest that most melanomas do not arise in pre-existing naevi, and accordingly public educational programs for the early detection of melanoma should focus on looking for changes in previously normal skin as well as in pre-existing moles. PMID- 2095739 TI - Retinoid-induced haemorrhagic bullae in Darier's disease. AB - Haemorrhagic epidermal bullae developed in a patient with Darier's disease undergoing long term treatment with the retinoid, etretinate. We suggest that these lesions result from cumulative toxic effects of long term retinoid therapy upon the abnormal keratinocyte found in Darier's disease. PMID- 2095740 TI - Repeat hepatic resections for colorectal metastases. AB - We identified 106 patients who had undergone complete resection of isolated colorectal hepatic metastases. Nine of these patients subsequently underwent repeat liver resections for isolated hepatic recurrences. The median follow-up for these patients was 21 months. One postoperative death was related to the second hepatectomy. At the time of last follow-up, five patients were alive and free of recurrent disease at 9, 19, 31, 50, and 67 months after their second hepatic resection. The remaining three patients were alive, but disease had recurred 11 months after resection in the first patient, 12 months after resection in the second, and 18 months after resection in the third. Among these three patients, two had solitary pulmonary nodules, which were resected, and one had unresectable liver disease. Our experience and a review of the literature suggest that repeat hepatic resection for isolated colorectal metastases can result in long-term survival in selected patients. PMID- 2095741 TI - Radiation-induced energy migration within solid DNA: the role of misonidazole as an electron trap. AB - The "in-pulse" luminescence emission from solid DNA produced upon irradiation with electron pulses of energy below 260 keV has been investigated in vacuo at 293 K to gain an insight into the existence of radiation-induced charge/energy migration within DNA. The DNA samples contained misonidazole in the range 3 to 330 base pairs per misonidazole molecule. Under these conditions greater than 90% of the total energy is deposited in the DNA. The in-pulse radiation-induced luminescence spectrum of DNA was found to be critically dependent upon the misonidazole content of DNA. The luminescence intensity from the mixtures decreases with increasing content of misonidazole, and at the highest concentration, the intensity at 550 nm is reduced to 50% of that from DNA only. In the presence of 1 atm of oxygen, the observed emission intensity from DNA in the wavelength region 350-575 was reduced by 35-40% compared to that from DNA in vacuo. It is concluded that electron migration can occur in solid mixtures of DNA over a distance of up to about 100 base pairs. PMID- 2095742 TI - Variable series elasticity accounts for Fenn effects of skeletal and cardiac muscles. AB - The Fenn effect differs between skeletal and cardiac muscles in the magnitude of energy consumption of shortening contraction relative to isometric contraction at the same preload. The former is typically greater than the latter in the skeletal muscle, whereas the former is smaller than the latter in the cardiac muscle. The present theoretical study examined whether the different Fenn effects could be accounted for by different compliances of the series elasticity (SE) in different muscles. A two-element model consisting of an idealized contractile element (CE) and an SE was used. The compliance of the SE was assumed to be variable. Results show that the skeletal Fenn effect can be simulated when SE is stiff and the cardiac Fenn effect can be simulated when SE is compliant. Moreover, when SE is compliant the total work of CE approximates for force-length area, which has been proposed as a measure of the total mechanical energy and shown to correlate linearly with myocardial oxygen consumption. PMID- 2095743 TI - Diaphragmatic fatigue is associated with decreased inositol 1,4,5-trisphosphate formation. AB - The ability of the rat diaphragm to produce inositol 1,4,5-trisphosphate (InsP3) in response to a maximal contractile stimulus was determine in vitro in both fatigued and nonfatigued diaphragms. InsP3 was produced during a maximal contraction of the diaphragm. After inducing fatigue, there was a significant reduction in the production of InsP3 compared with that in nonfatigued muscle. The maximal force generated by the diaphragm was also decreased after fatigue. A significant positive linear correlation was found between the force developed by the diaphragm and the amount of InsP3 liberated. PMID- 2095744 TI - Bilateral pneumothorax as a presenting feature of metastatic angiosarcoma of the scalp. PMID- 2095745 TI - Ethical considerations in testing victims of sexual abuse for HIV infection. PMID- 2095746 TI - Comparative bacterial clearances of muscle and skin/subcutaneous tissues with and without dead bone: a laboratory study. AB - Seventeen New Zealand White rabbits underwent implantation of three different concentrations of bacteria and a sterile saline control solution with and without dead autologous bone in eight separate muscular and eight separate subcutaneous sites. Following a period of 1 week, each site was surgically explored and samples of tissue were taken for histology and quantitative culture. Results reveal that final bacterial concentrations in the subcutaneous sites were significantly lower than in the muscle sites (p less than or equal to 0.0001) for each concentration of bacteria, with and without dead bone. Dead bone resulted in very significantly greater bacterial concentrations in both subcutaneous and muscle sites. Clinically, these results indicate that a thorough bony wound debridement is more important than the type of tissue used to close the wound. Flap tissue should be selected with regard to the perfusion, contour, and appearance of the recipient site. PMID- 2095747 TI - Coffee consumption and blood pressure: a randomized, crossover clinical trial. AB - OBJECTIVE: To examine the effect of moderate coffee consumption on blood pressure over a prolonged period of time. Previous work in this area has used primarily purified caffeine. DESIGN: A prospective, randomized, crossover clinical trial. SETTING: A hypertension specialty outpatient clinic at the University of Tennessee, Memphis. PATIENTS: Healthy, young, white men who were moderate coffee drinkers (less than 6 cups/day) were recruited. Twenty-four subjects were randomized and 21 (average age 35.5 years) completed the trial. INTERVENTIONS: Subjects were randomized to one of two groups: Group A drank three or more cups of coffee/day for two months, then crossed over to abstaining from coffee for two months; group B abstained from coffee first, then crossed over to drinking coffee. Only filter-brewed coffee was used. Subjects were seen at monthly intervals for blood pressure measurements. MEASUREMENTS AND MAIN RESULTS: The average coffee consumption was 3.6 cups/day during the coffee-drinking phases. There was no difference between the coffee-drinking phase and the abstention phase in either systolic blood pressure (110.1 mmHg vs. 108.0 mmHg, respectively; 95% CI of difference -7.3, 2.5) or diastolic blood pressure (67.2 mmHg vs. 69.6 mmHg, respectively; 95% CI of difference -2.2, 6.4). CONCLUSIONS: Moderate daily consumption of coffee does not elevate blood pressure. PMID- 2095748 TI - Transient stress lymphocytosis during crisis of sickle cell anemia and emergency trauma and medical conditions. An immunophenotyping study. AB - Transient absolute lymphocytosis of peripheral blood has been described in "stress"-related emergency trauma and medical conditions. There are no reports of this phenomenon in patients with sickle cell anemia with vaso-occlusive crisis. We studied initial and follow-up immunophenotypic characteristics of 10 adult patients with sickle cell anemia in crisis and 15 adult patients with emergency conditions who presented with absolute lymphocytosis. On admission, both groups demonstrated increases in the numbers of CD20+ B cells and T cells of the CD2, CD4, CD8, and CD56 (NKH-1) phenotypes compared with control values. Findings in both groups of patients mimicked the results of parenteral epinephrine administration: a pan-B and -T lymphocytosis with marked increase in CD56 (fourfold to fivefold) and CD8 cells (threefold to fourfold) as well as moderate increases in CD20 and CD4 cells (twofold), resulting in a decrease in the CD4/CD8 ratio compared with control values. In patients with sickle cell anemia, there was an expected increase in the CD56 and CD4 populations; however, CD8 cells only doubled at the time of crisis. Therefore, the CD4/CD8 ratio was normal compared with control values. CD20+ B cell numbers exceeded those seen in the patients with medical and trauma emergencies. Elevated corticosteroid levels have been measured after injury in previous studies. Parenterally administered cortisol produces a lymphocytopenia after 4 to 6 hours that selectively decreases T cells. At 10 to 38 hours after admission, there was a marked reduction in the number of T cells in both groups of "stressed" patients, probably reflecting at least partial effects of endogenous corticosteroids. In contrast to the patients with medical and trauma emergencies, the mean lymphocyte count in the patients with sickle cell anemia remained elevated in the "high normal" range and consisted of increased numbers of B cells and CD4 cells. This finding persisted in the patients with sickle cell anemia for up to 3 months after presentation. The lymphocyte responses in both groups probably reflect interactions between adrenergic and steroidal factors. PMID- 2095749 TI - Molecular genetic basis of the diagnosis of hematopoietic neoplasms. AB - New discoveries regarding the molecular genetic basis of lymphoma have begun to shape a model of lymphomagenesis that affords investigators an opportunity to measure the clinical effects of specific altered genes in a major form of human cancer. PMID- 2095750 TI - Estimate of the maximal daily dietary intake of butylated hydroxyanisole and butylated hydroxytoluene in The Netherlands. AB - The daily dietary intake of the phenolic antioxidants butylated hydroxyanisole (BHA) and/or butylated hydroxytoluene (BHT) was estimated using data obtained from a nationwide dietary record survey carried out in The Netherlands in 1987/1988. The estimates were based on the fat content of selected food categories and their respective maximum permitted levels of BHA and/or BHT. The results indicate that it is unlikely that the current acceptable daily intake for BHA (0-0.05 mg/kg body weight) is surpassed, even in individuals with an extremely high caloric intake, except in extreme cases in 1-6-year-olds. However, it cannot be excluded that the acceptable daily intake for BHT (FAO/WHO: 0-0.125 mg/kg; EEC: 0-0.05 mg/kg) is exceeded in all age and sex groups, but particularly in children aged 1-6 years. PMID- 2095751 TI - Evolution of social services for children with emotional disorders. AB - In this article, the authors examine the evolution of America's varied and often conflicting responses to the needs of its children--more specifically, the historical responses to dependent, neglected, and emotionally disordered children. The authors discuss America's historical ambivalence about whether to institutionalize children or keep them with their families, the relationship between social work professionals and clients, and the lessons that can be learned and applied to current practice. The analysis suggests that social work challenge some of the assumptions upon which prior service and advocacy efforts have been based. The magnitude of the current service system problems warrants a family-centered advocacy stance aimed at improving community-based services. This approach could free social workers to operationalize key values of the profession. PMID- 2095752 TI - Severe hemolysis after incomplete mitral valve repair. AB - We report 2 cases of severe intravascular hemolysis after mitral valve repair using a Duran annuloplasty ring. In both patients residual mitral regurgitation was present, hemolysis was severe enough to warrant a second operation, and hemolysis ceased immediately after the second operation. We believe that a high velocity regurgitant jet directed toward the cloth-covered annuloplasty ring was responsible for the hemolysis in both patients. PMID- 2095753 TI - Minimal residual disease in childhood B-lineage lymphoblastic leukemia. Persistence of leukemic cells during the first 18 months of treatment. AB - BACKGROUND: Whether patients in clinical remission for acute lymphoblastic leukemia (ALL) continue to harbor leukemic cells is not known, because methods of detecting residual malignant cells have not been sufficiently sensitive. This information might be useful for predicting recurrence and determining the duration of therapy. METHODS: Using a sensitive new method--identifying complementarity-determining region III sequences with the polymerase chain reaction--we estimated the number of residual leukemic cells in the bone marrow of eight children with B-lineage lymphoblastic leukemia before and after remission. RESULTS: Induction chemotherapy produced a 3-to-4-log reduction in the number of leukemic cells. In all samples obtained up to 18 months after diagnosis, however, 0.004 to 2.6 percent of bone marrow nucleated cells were residual leukemic cells. Among the four patients studied more than 18 months after diagnosis, three had no detectable leukemic cells in marrow samples. Despite this, one of them, who was no longer receiving therapy, had a central nervous system relapse. In one patient receiving maintenance chemotherapy, there was a 60-fold increase in leukemic cells three months before bone marrow relapse. CONCLUSIONS: The complete disappearance of leukemic cells (or their reduction below our method's threshold of detection, 1 in 100,000 cells) may be necessary to achieve a cure of ALL. The quantification of residual leukemic cells in serial marrow aspirates during therapy may allow the early detection of relapse. PMID- 2095754 TI - Earlobe crease and atherosclerosis. An autopsy study. AB - The association between earlobe crease (ELC) and coronary and aortic atherosclerosis in 100 autopsied men ranging in age from 50 to 79 years, who died free of vascular diseases or related conditions, was studied in conjunction with blood pressure and serum total cholesterol (TC) levels. Earlobe crease was graded and defined as groups 1, 2, and 3 according to the depth and length in both ears. The extent of atherosclerosis in the coronary arteries and aortas was visually graded. Coronary atherosclerosis was significantly more severe in group 3 in all the decades examined than in groups 1 or 2. Aortic atherosclerosis in group 3 was significantly greater than in group 1 in all the decades examined, and was greater than in group 2 in the seventh and eighth decades. The TC level was significantly higher in group 3 than in groups 1 or 2 except in the sixth decade. Multivariate regression analyses demonstrated that the degree of ELC was dependent on the extent of coronary and aortic atherosclerosis, but was independent of age. Conversely, the extent of coronary atherosclerosis was dependent on the degree of ELC, but was independent of age. The extent of aortic atherosclerosis was, however, dependent not only on the appearance of ELC and TC, but on age. It is thus concluded that ELC provides a significant external marker for atherosclerosis and may reflect a persistent overload of atherosclerosis risk factors, such as TC. PMID- 2095755 TI - A rational approach to liver transplantation for the alcoholic patient. PMID- 2095756 TI - Changes in myocardial high-energy phosphate stores and carbohydrate metabolism during intermittent aortic crossclamping in dogs on cardiopulmonary bypass at 34 degrees and 25 degrees C. AB - The effect of cooling to 25 degrees C on myocardial metabolism was studied during four periods of global ischemia (10 minutes each) followed by 15 minutes of reperfusion in dogs on cardiopulmonary bypass. Systemic and heart temperature at normothermia (group N, 34 degrees C; n = 15) was compared with general hypothermia (group H, 25 degrees C; n = 16). Before and at the end of each aortic crossclamp period in small myocardial biopsy specimens the adenosine triphosphate, creatine phosphate, inorganic phosphate, glycogen, and lactate content was analyzed. Also, lactate and inorganic phosphate were measured in the coronary effluents during the repetitive periods of reperfusion. Hemodynamic function was not different at 60 minutes after cardiopulmonary bypass compared with pre-cardiopulmonary bypass values, and was not different between the groups N and H. The tissue content of adenosine triphosphate and glycogen decreased progressively during the experimental period, resulting in slightly depressed values in both groups at the end of cardiopulmonary bypass. Pronounced effects of ischemia and reperfusion on tissue content of creatine phosphate, inorganic phosphate, and lactate were observed after each period of ischemia. The net decrease in tissue creatine phosphate content was not different between groups N and H (41 +/- 4 versus 38 +/- 4 mumol.gm-1 dry weight; mean +/- standard error of the mean) after 10 minutes of ischemia. However, during ischemia the net inorganic phosphate increase in myocardial tissue was significantly higher in group H (70 +/- 7 mumol.gm-1) than in group N (44 +/- 3 mumol.gm-1). These findings do not support the notion that myocardial protection is improved during hypothermia. Moreover, quantitatively the release of inorganic phosphate and lactate did not correlate with the amount accumulated in the myocardial tissue during the preceding periods of ischemia. The release appeared to be temperature dependent, that is, significantly reduced at 25 degrees C. The present data demonstrate why clinical outcome is satisfactory in both surgical procedures, when in general the periods of aortic crossclamping do not exceed 10 minutes each and the reperfusion periods in between the ischemic episodes last about 15 minutes. Besides, the findings indicate that hypothermia is not strictly necessary under these circumstances. PMID- 2095757 TI - Opioids in postoperative pain relief. PMID- 2095758 TI - Ascorbic acid is cytotoxic to dividing human Tenon's capsule fibroblasts. A possible contributing factor in glaucoma filtration surgery success. AB - Successful glaucoma filtration surgery depends on the incomplete healing of the surgical wound, with formation of a filtration bleb. In most other tissues, however, complete healing is the rule. I have explored the possibility that the high concentration of ascorbic acid normally present in aqueous humor inhibits wound healing after filtration surgery. At the concentration normally present in aqueous humor (1.1 mmol/L), ascorbic acid decreased the plating efficiency of cell suspensions of human Tenon's capsule fibroblasts by a mean (+/- SD) of 40% +/- 10%. When added to low-density monolayer cultures of fibroblasts, ascorbic acid decreased the cell number by 90% +/- 5%, an effect that was completely prevented by catalase. When added to confluent cultures, the cell number was decreased by only 14% +/- 2%. If ascorbic acid has similar effects on fibroblasts in vivo, it may contribute to the incomplete wound healing that characterizes successful glaucoma surgery. PMID- 2095759 TI - Transcutaneous oxygen tensions in assessing the treatment of healed venous ulcers. AB - Transcutaneous oxygen tension (Ptc,O2) was assessed as an indicator of risk of reulceration in 68 limbs with healed venous ulcers. Ptc,O2 was also used to assess two methods of ulcer prophylaxis. Measurements were made over the gaiter skin, the healed ulcer and the upper arm. The results were expressed as a ratio of the lower limb readings over those taken from the arm. Patients were randomized, after the ulcer had healed, to elastic stockings and stanozolol, or elastic stockings and surgical ligation of incompetent superficial veins. Patients who declined to participate in the study were prescribed elastic stockings only. Those limbs remaining healed at 12 months had Ptc,O2 ratios remeasured. The Ptc,O2 ratios from limbs that reulcerated were not significantly lower than those from limbs remaining healed. The Ptc,O2 ratio was significantly increased in limbs treated by stanozolol and elastic stockings (P less than 0.05) and by surgery and elastic stockings (P less than 0.05). There was no significant increase in Ptc,O2 in limbs treated by elastic stockings alone. In those treated by surgery and elastic stockings, there was a significant improvement in limbs with normal deep veins (P less than 0.01), but not in limbs with post-thrombotic changes on ascending phlebography. Although these two methods of ulcer prophylaxis improve the Ptc,O2 ratio, a high ratio has not been shown to be beneficial in preventing ulcer recurrence. PMID- 2095760 TI - Limitations of tumour markers in screening. PMID- 2095761 TI - Medical education in Rhode Island, 1990. PMID- 2095762 TI - AIDS vaccine conference: is "more" better? PMID- 2095763 TI - The inherited character of cancer--an historical survey. PMID- 2095764 TI - Indications for office radiographs. AB - Radiology is an essential part of the family physician's office practice. Like most diagnostic tools, radiographs can provide valuable information, but they also have the potential to be abused. One of the first tasks in ensuring optimal use of any procedure is to establish criteria for proper patient selection. This article is a review of general and specific indications for office radiographs on both symptomatic and asymptomatic patients based on published expert consensus and studies that have examined indications for radiographs using clinical criteria. For symptomatic patients, indications are discussed for the following radiographs: extremities (traumatic and nontraumatic), skull, abdomen, chest, orbits, sinuses, facial bones, and spine. Indications for asymptomatic patients are discussed with specific attention to lumbosacral spine and chest radiographs. When appropriate indications are followed, the physician can avoid the problem of overuse and its consequent radiation and economic burdens, as well as the problem of underuse with its risk of incomplete evaluation. PMID- 2095765 TI - Chlamydia trachomatis infection in Native American women in a southwestern tribe. PMID- 2095766 TI - Childhood amnesia and distinctions between forms of memory: a comment on Wood, Brown, and Felton. AB - Recently, Wood and his colleagues (1989) presented a case of childhood amnesia as evidence against the distinction between declarative and procedural memory that has sometimes been applied to human amnesia. Their argument was based on the observation that their patient showed some progress in school over the years, i.e., acquired some declarative knowledge, despite severely impaired day-to-day memory ability. We briefly review their case, together with a carefully studied second case of childhood amnesia not mentioned by Wood et al. Their argument is wrong in several ways. First, the utility of the declarative/procedural distinction for amnesia, or the utility of any other distinction between memory systems, depends on whether or not one kind of memory is impaired selectively, not on the severity of the impairment. In particular there is no requirement that one kind of memory be totally absent. Second, they have not provided the data necessary to support their argument; namely, data showing that the amount of declarative knowledge accumulated during years in school was better than would have been expected given the capacity for moment-to-moment or day-to-day memory. Indeed, the patient's moment-to-moment memory ability is better than represented, and the patient's progress in school was abnormally slow. Third, it is not clear that academic achievement scores provide a direct measure of declarative memory abilities (skill learning and recovery of function may also have contributed). We conclude that the evidence from childhood amnesia is fully consistent with the proposal that amnesia reflects a selective impairment in the formation of long term declarative memory. PMID- 2095767 TI - Amphetamine psychosis. PMID- 2095768 TI - Oral effects of chronic alcoholism. PMID- 2095769 TI - Transverse myelitis and antiphospholipid antibodies. PMID- 2095770 TI - Absence of macrocytosis in MS. PMID- 2095772 TI - Addressing the shortage of occupational physicians. PMID- 2095771 TI - Thyroid dysfunction. PMID- 2095773 TI - Bayes' theorem should be considered when making decision limits. PMID- 2095774 TI - Features of Turner's and DiGeorge's syndromes with X;22 translocation. PMID- 2095775 TI - PUVA-induced itching and skin pain. PMID- 2095776 TI - Statistical significance in medical literature. PMID- 2095777 TI - [Erythrocyte glutathione and urinary thioethers in smokers]. AB - The carcinogenic mechanism of smoking is related with the production of electrophilic reactants and their possible covalent binding with DNA. On the other hand, there are detoxifying mechanisms such as glutathione-S-transferase, which results in mercaptopuric derivatives that are excreted in the urine. The integrity of the erythrocyte membrane is maintained by reduced glutathione among other factors. In the present study, the concentrations of erythrocyte reduced glutathione (GSH) and urinary thioethers (UT) were measured in a sample of 81 subjects divided in two groups. Group I: 30 nonsmokers; group II: 51 smokers, subdivided in group IIA (26 individuals smoking 10-20 cigarettes/day) and group IIB (25 individuals smoking more than 20 cigarettes/day). In the present study, the usefulness of GSH and UT as markers of collective internal contamination and of individual risk regarding tobacco exposure were evaluated. A higher concentration of GSH was found in smokers than in nonsmokers (F = 6.84, p less than 0.02). Regarding VT elimination, a significant increase in these parameters was found in association with the grade of smoking (p less than 0.05). They were higher in the subjects from the subgroup IIB than in the subgroup IIA (moderate smokers). PMID- 2095778 TI - Effects of diisopropyl phosphorofluoridate (DFP) on CA3 and CA1 responses in rat hippocampus. AB - Diisopropyl phosphorofluoridate (DFP), an insecticide, is a potent anticholinesterase that binds essentially irreversibly to acetylcholinesterase, resulting in severe, acute neurologic pathology, and less severe, but longer lasting, delayed neuropathy. We report here on the short-term effects of bath applied DFP on extracellularly recorded responses from CA3 and CA1 of rat hippocampus. Exposure to 10 microM DFP evokes low amplitude, spontaneous bursts in CA3 generally within 10 minutes, and the bursting does not reverse with washing. The CA1 neuronal population usually bursts synchronously with CA3, but the population events are of low amplitude and sometimes not detectable, implying a differential sensitivity to DFP. These effects were partially blocked by the muscarinic antagonist atropine, while the cholinergic antagonist gallamine had little effect. Also, the reversible anticholinesterase physostigmine could, within temporal limits, protect slices from DFP's effects, implicating the cholinergic system as the probable mediator in the first stages of DFP-induced epileptogenesis. PMID- 2095779 TI - Increase in glial fibrillary acidic protein following neural trauma. AB - Immunohistochemical staining and quantitative evaluation of glial fibrillary acidic protein (GFAP) were carried out in a stab wound model of neural trauma in the rat. Increased GFAP staining was detected in reactive cortical astrocytes in the vicinity of the wound at 3, 7, and 30 d following injury. Western blots immunostained for GFAP also demonstrated an increase in GFAP in homogenates from the lesioned cortex, compared to the contralateral control side, on days 3, 7, and 30. Specific activity of GFAP expressed as a ratio of lesion/control values showed a fivefold increase from day 0 to day 7, with no further change on day 30. We conclude that neural trauma elicits a quantitative increase in GFAP in the rat cortex during the first week following injury. This increase correlates with both astrocyte hyperthrophy and proliferation. Thus, specific activity of GFAP is a reliable indicator of the onset and progression of astrogliosis in neural trauma. PMID- 2095780 TI - Modification of malathion induced neurochemical changes by adrenalectomy in rats. AB - The neurochemical changes induced by malathion, an organophosphate compound, were determined in rats. Maximal changes were found in the brain 2 h after the administration of malathion in a dose of 500 mg/kg ip. The activities of cholinesterase and succinic dehydrogenase were reduced whereas those of glycogen phosphorylase, phosphoglucomutase, and hexokinase were increased; the lactate content of brain was also increase. In malathion treated adrenalectomized animals, changes in the activities of cerebral cholinesterase and succinic dehydrogenase were still present; other changes were, however, abolished by adrenalectomy. Activities of certain enzymes, glucose-6-phosphatase, glucose-6 phosphate dehydrogenase, and lactate dehydrogenase were not significantly altered by malathion in normal or adrenalectomized animals. The results indicate that cerebral cholinergic mechanism in malathion treated animals was not modified by adrenalectomy which, however, abolished or reduced changes in the activities of certain glycolytic and glycogenolytic enzymes that are involved in the utilization or metabolism of glucose. The brain lactate content in malathion treated adrenalectomized animals was, also, not significantly different from the control values, suggesting that modification of induced changes by adrenalectomy. PMID- 2095781 TI - Seasonal serotonin uptake changes in healthy subjects. AB - Platelet 5-hydroxytryptamine (5HT) uptake was measured in 12 healthy subjects in the spring, summer, and late autumn. The uptake was performed according to the method of Arora and Meltzer (1981). The maximal velocity of 5HT uptake was higher in the spring and in summer than in the autumn. In addition, a significant negative correlation between the Michaelis constant and the photoperiod was observed in spring. These findings seem to indicate the possible evidence of physiological season-related changes of platelet 5HT uptake that may be linked to the photoperiod. PMID- 2095783 TI - Reduced myelinogenesis and recovery in hyperphenylalaninemic rats. Correlation between brain phenylalanine levels, characteristic brain enzymes for myelination, and brain development. AB - In a previous paper (Burri et al., 1990), we have shown that experimental hyperphenylalaninemia (hyper-Phe) in 3-17 d-old rats leads to reduced myelinogenesis. Such treated rats recover during a 6 w low phenylalanine (Phe) period between days 17 and 59. In order to get more detailed information about the disturbed myelinogenesis and recovery, we measured in hyper-Phe rats the developmental pattern of two brain enzymes typical for myelination, cerebroside sulfotransferase (CST), and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), and other developmental parameters. Further, we correlated brain Phe levels with the brain damage in hyper-Phe rats, and we measured brain acetylcholinesterase (AChE) as a neuronal marker. Experimental hyper-Phe rats, injected between postnatal days 3 and 17 with alpha-methylphenylalanine and phenylalanine, showed a delayed age-dependent increase of CST activity, compared to that of controls. In hyper-Phe rats, CST peak activity was reached 2-4 d later, and was lower than in controls. The age-dependent decrease of the CST activity, however, started in test and control rats at the same time, at day 21. Between days 24 and 59, hyper Phe rats had normal CST activity. CNP activity in hyper-Phe rats was lower than in controls from day 10 to 35, and recovered to normal values between days 35 and 59. Our results indicate that recovery from reduced myelinogenesis is possible after the period of fast myelination without compensatory increased CST activity. Further, the brain damage in test rats with Phe levels higher than average is more severe than in test rats with Phe levels lower than average; and there is no effect of hyperphenylalaninemia on brain neurons containing AChE. PMID- 2095782 TI - Modulatory effects of phosphatidylserine on the binding of muscarinic cholinergic receptor ligands. Studies in vitro and in vivo. AB - The modulation of the binding of muscarinic cholinergic receptor ligands by phosphatidylserine purified from bovine cerebral cortex (BC-PS) was examined in vitro and in vivo. The enrichment of bovine cerebral cortical synaptosomal membranes with BC-PS, using a fusion technique, produced a concentration dependent decrease in the affinity (increase in Kd) of [3H]quinuclidinyl benzylate (3H-QNB) specific binding to muscarinic acetylcholine receptors (mAChR), without changes in their maximal number (Bmax). Similar results were observed when [3H]oxotremorine (3H-OXO) was used to label a high affinity subpopulation of mAChR. On the other hand, preincubation of BC-PS liposomes with synaptosomal membranes in a nonoptimum fusion condition (at pH 7.4) did not alter the binding properties of both radioligands. Fusion experiments using a pure phosphatidylserine preparation from spinal cord revealed a similar decrement in the affinity of 3H-QNB specific binding. Five day's intraperitoneal (i.p.) administration of 15 mg/kg of BC-PS liposomes in rats increased the maximal number of cerebral cortical binding sites for 3H-OXO. Scatchard analysis revealed no changes in the apparent dissociation constant. This modification is selective in relation to the neural structure studied. Thus, BC-PS treatment did not modify 3H-OXO binding in the hippocampal formation and cerebellum. In contrast, parallel experiments using the muscarinic antagonist 3H-QNB showed no alteration in the binding properties of mAChR. Five day's i.p. administration of 15 mg/kg/d of phosphatidylcholine from bovine cerebral cortex (BC-PC) liposomes produced quite similar results to those obtained with BC-PS. These results indicate that mAChR are under the modulatory action of phosphatidylserine (PS) and phosphatidylcholine (PC), and suggest that this endogenous phospholipids may play a regulatory role on the mAChR. The possible implications of these findings on the effects of PC or PS treatment in neurological disorders involving a decrease in central cholinergic functions are discussed. PMID- 2095784 TI - Immunization with cholinergic cell bodies induces histopathological changes in rat brains. AB - We have previously shown that sera from patients with Alzheimer's disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergic Torpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization with Torpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease. PMID- 2095785 TI - 1,25-Dihydroxyvitamin D3 affects the synthesis, phosphorylation and in vitro calmodulin binding of myoblast cytoskeletal proteins. AB - Incubation of chick embryo myoblasts with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (10(-10) M, 24 h), markedly stimulated the incorporation of [3H]leucine into total cytoskeletal proteins and this effect was abolished when the sterol treatment was performed in the presence of cycloheximide or actinomycin D. 1,25(OH)2D3 selectively stimulated the de novo synthesis of several proteins with apparent molecular masses (isoelectric points) of 220 kDa (6.1 and 9.7), 150 kDa (7.5), 110 kDa (7.2), 68 kDa (9.5, 7.5 and 4.5), 50 kDa (8.5), 44 kDa (6.3), 27 kDa (7.8) and 15 kDa (5.5). Labelling of proteins with [125I]calmodulin after their separation on SDS-polyacrylamide gels showed that 1,25(OH)2D3-dependent protein of 110 kDa is the major calmodulin-binding component of myoblasts cytoskeleton. In addition, the sterol increased the phosphorylation of several cytoskeletal proteins including that of 110 and 15 kDa whose synthesis potentiates. PMID- 2095786 TI - Rat liver DNase I-like activity and its interaction with actin. AB - Monomeric G actin, total actin and the F:G actin ratio were determined in the rat liver cytosol and nucleoplasm by measuring the inhibition of standard crystalline DNase I. Actin was purified from rat liver nucleoplasm by Sephadex filtration. Accompanying the considerable amount of actin an endogenous DNase I like activity was found in rat liver cytosol and nucleoplasm. It was shown, that similarly to DNase I from bovine pancreas the liver DNase was inhibited by mammalian and avian skeletal muscle actin as well as by endogenous liver actin, as verified by electrophoresis of DNase containing extracts on polyacrylamide gels with incorporated DNA. PMID- 2095787 TI - Tracing the human metabolism of stable isotope-labelled drugs by ex vivo NMR spectroscopy. A revision of S-carboxymethyl-L-cysteine biotransformation. AB - A direct structural identification, and quantitative assessment below the 50 nmol/ml level, of the full pattern of renally excreted metabolites is made possible by 13C NMR measurements of untreated urine samples when stable isotope labelled (13C) drug analogues are administered to humans. The full potential of the new ex vivo NMR approach is exemplified by a study, for a group of volunteers, of S-carboxymethyl-L-cysteine metabolism. The metabolic sulphoxidation pathway of S-carboxymethyl-L-cysteine in man, accepted so far, needs to be profoundly revised on the basis of the 13C NMR results. PMID- 2095788 TI - Comparative luminescence of rat liver Cu-thionein and its chemically synthesized alpha-domain. AB - A peptide corresponding to the alpha-domain of rat liver metallothionein-2 was chemically synthesized employing the solid phase peptide synthesis technique. Its luminescence properties that depend on the coordinated Cu(I) have been studied using luminescence spectrometric titration in the presence of Cu(I). Unlike the intact metallothionein which has been converted into the Cu species, the emission and excitation spectra of the Cu-alpha-fragment showed a red shift by 20 nm and 65 nm, respectively, suggesting a more compact and stable luminophore in the alpha-domain. Saturation of Cu(I) coordination was reached in the presence of 6.5 mol eq Cu(I) when the alpha-fragment was used and 12 mol eq Cu(I) were specifically bound by the intact metallothionein. The emission bands were homogeneous and no decline of the cluster structure was observed when excessive Cu(I) was added after saturation. A rearrangement of the Cu-cluster in metallothionein during its formation seems to be plausible. PMID- 2095789 TI - The effect of glutathion on the reaction of cis-and trans diamminedichloroplatinum(II) with DNA. AB - Differential pulse polarography study was used to investigate the influence of glutathion on cis- and trans-DDP induced alterations of DNA structure. Though the applied concentration of glutathion has no effect on the reaction on DNA with cis DDP, it greatly modifies the reaction with trans isomer. This may be an important reason for the ineffectiveness of the trans-DDP as an antitumor drug. PMID- 2095790 TI - Chemotherapy of filariasis--on the search of new agents effective on the reproductive system of female adult worms. AB - The design and synthesis of a series of alkyl 5(6)-substituted benzimidazole-2 carbamates (1-13), 7-chloro-4-(4-substituted phenyl)aminoquinolines (14-16), 1,2 dimethyl-3-methoxy-carbonyl-4,5-disubstituted pyrroles (17-19) and some compounds belonging to the class pimelonitrile (20), dihydroquinoline (21), pyridine (22), pyridoquinoline (23) and tetrahydro-pyrimidine (24) have been carried out as possible antifilarial agents. All these compounds have been evaluated for their activity against male and female adult worms of Litomosoides carinii in cotton rats. The effect of these compounds was also observed on the reproductive system (condition of developing microfilariae and their release from uterus) of adult female worms. In this study, three types of compounds were discovered: (a) those which showed activity on both the male and female adult worms and also had sterilizing effects on surviving adult females (1-3, 6-9, 13, 19), (b) those which only sterilized the adult females (14-16, 21, 24), and (c) those which had no effect on female reproduction but killed only adult worms (4, 5, 11, 12, 17, 18, 20, 22, 23). This tends to open up a new avenue in the chemotherapy of filariasis and the future scope of work on chemosterilization of adult females has been discussed. PMID- 2095791 TI - Membrane conductance changes associated with the response of motion sensitive insect visual neurons. AB - Intracellular recordings and impedance measurements from directionally-selective visual interneurons of the lobula plate of flies show that during motion, transmembrane conductance increases during both depolarizing responses to preferred directions and hyperpolarizing responses to anti-preferred directions. This provides direct evidence that these interneurons are postsynaptic to two separate populations of excitatory and inhibitory input elements. PMID- 2095792 TI - Simulations of a fox-rabies epidemic on an island using space-time finite elements. AB - The two-dimensional reaction diffusion equations for the spread of rabies in a logistically growing fox population are solved numerically. The method, based upon Galerkin's approach, uses space-time finite elements. The numerical model is shown, quantitatively, to possess the essential features of earlier one and two dimensional models and to reproduce the values of field data accurately. A more realistic illustration of the use of the model, a study of the spread of rabies over the Isle of Anglesey, is then discussed. PMID- 2095793 TI - Automatic control and directed cell movement. Novel approach for understanding chemotaxis, galvanotaxis, galvanotropism. AB - It is shown that chemotaxis, galvanotaxis, galvanotropism, etc. are functions of cells having a goal-seeking system. Even when the involved physicochemical signals are unknown, the cellular system can be treated phenomenologically like an automatic controller having a closed-loop feedback system. The model is verified by means of galvanotaxis and chemotaxis data of human granulocytes. The galvanotaxis and chemotaxis coefficient quantifying the cellular sensibility can be predicted from the coefficient which characterizes the deterministic part of the signal transduction/response system of the cell divided by the coefficient which characterizes the noise strength in the cellular signal transduction/response system. The model is not restricted to directed movement of granulocytes. It is very general and can be applied to any cell type for directed phenomena like chemotaxis, galvanotaxis, phototaxis, magnetotaxis, directed growth, etc. The virus-disturbed directed migration of granulocytes is discussed and it is shown that the virus alters the deterministic part of the cellular controller. PMID- 2095794 TI - Determination of germanium in some plants and animals. AB - The Ge contents of plants and animals were investigated by a wet ashing procedure by hydride generation and inductively coupled plasma atomic emission spectrometry with flow injection. The analytical results obtained indicated that Ge contents widely vary in plant and animal kingdoms in the range of 8-302 ppb. PMID- 2095795 TI - Synergistic action of clotrimazole and certain anionic surfactants may be due to ion pair formation. AB - A synergistic effect of clotrimazole and certain anionic surfactants against a strain of Candida albicans was confirmed. Measurement of apparent partition coefficients indicated that lipophilic ion pairs between clotrimazole and anionic surfactants were formed. It is suggested that the synergistic effect of the drugs may be due to ion pair formation. PMID- 2095796 TI - Relative bioavailability of (+/-)-verapamil hydrochloride administered in tablets and chewing gum. AB - The absorption of verapamil administered orally in chewing gum (23.4-29.7 mg) and perorally in tablets (80 mg) to seven healthy volunteers in a study using an open cross-over design, was compared. Following peroral administration the mean +/- SD AUC/D was (5.4 +/- 1.9) x 10(-3) micrograms ml-1 h per microgram dose and after administration of chewing gum (6.6 +/- 2.3) x 10(-3) micrograms ml-1 h per microgram dose (NS). The AUC ratio of verapamil to the metabolite norverapamil was 1.5 after oral and 0.8 after peroral administration, indicating that a part of the verapamil administered in chewing gum was absorbed through the oral mucosa. PMID- 2095797 TI - The anti-inflammatory activity of 5H-dibenz[c,e]azepine-5,7(6H)dione, 6,7-dihydro 5H-dibenz[c,e]azepine, N-benzoylbenzamide and 1H-benz[d,e]isoquinoline 1,3(2H)dione derivatives in rodents. AB - A series of N-substituted 5H-dibenz[c,e]azepin-5,7(6H)dione, 6-substituted 6,7 dihydro-5H-dibenz[c,e]azepine, 1H-benz[d,e]isoquinoline-1,3(2H)dione and N benzoyl derivatives was shown to have anti-inflammatory and local analgesic activity in rodents. 6-(4-Chlorophenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated greater than 50% inhibition of induced edema and the writhing reflex at 25 mg/kg, I.P. in mice. 6-Methyl-6,7-dihydro-5H-dibenz[c,e]azepine and the N butyl and N-pentyl derivatives of the dibenz-[c,e]azepine and N-benzoylbenzamide series demonstrated potent activity in both screens. The 1H-benz[d,e]isoquinoline 1,3(2H)diones were generally less active than the other three chemical classes of agents tested. However, the 2-(methylthio)ethyl derivative of this series demonstrates good activity in both screens. These agents appeared to be as potent as the standards, indomethacin and phenylbutazone, as anti-inflammatory agents in these animal models. Selected agents, e.g. 6-(4-methylphenyl)-5H dibenz[c,e]azepin-5,7(6H)dione demonstrated anti-arthritic and anti-gout activities in rodents. The N-methyl and N-butyl derivatives of 6,7-dihydro-5H dibenz[c,e]azepine afforded good anti-pleurisy activity in rats at 25 mg/kg x 2. The agents which demonstrated potent anti-inflammatory action were found to inhibit acid lysosomal hydrolytic enzyme activities in mouse liver and macrophages at 10(-5) M concentrations. Trypsin, elastase and collagenase activities were also inhibited by the derivatives. Prostaglandin synthetase activity of bovine seminal vesicles and mouse macrophages was inhibited by the compounds at 10(-5) M concentrations. PMID- 2095798 TI - Pharmaceutical application of biomedical polymers. XXIX. Preliminary study on film dosage form prepared from chitosan for oral drug delivery. AB - The potential of chitosan films containing diazepam as an oral drug delivery was investigated in rabbits. The results indicated that a film composed of a 1:0.5 drug-chitosan mixture might be an effective dosage form that is equivalent to the commercial tablet dosage forms. The ability of chitosan to form films may permit its use in the formulation of film dosage forms, as an alternative to pharmaceutical tablets. PMID- 2095799 TI - Potential antitumor agents XVII (1). Cytotoxic agents from indole derivatives and their intermediates. AB - New indole derivatives and their intermediates were tested as cytotoxic agents on a culture of P388 leukemia cells. The aldehyde 2a was more active than the thiosemicarbazones 3a, b and the nitrosourea 14. The chloroacetyl derivatives 10, 11 were the most potent cytotoxic agents. PMID- 2095800 TI - Smooth muscle relaxing flavonoids from Alchornea cordifolia. AB - Alchornea cordifolia (Schum. & Thonn.) Muell. Arg. (Euphobiaceae) is widely distributed throughout tropical Africa, where it is used extensively in traditional medicine. Conditions for which the plant has enjoyed wide use are: coughs, gonorrhoea, yaws, ulcer, rheumatic pains, fever and bronchial troubles. This paper reports isolation of smooth muscle relaxing flavonoids from the leaves of the plant. PMID- 2095801 TI - The impact of chewing sugarless gum on the acidogenicity of fast-food meals. AB - The objective of this study was to evaluate the effect of chewing sorbitol gum on plaque pH following the ingestion of acidogenic fast-food meals. Plaque pH response was monitored using an indwelling wire-telemetry system in five adult panelists. From a pilot study with 12 fast-food meals, the most acidogenic breakfast, lunch and dinner were selected for this study. In the first test, the fasted, resting plaque pH was recorded for 5 minutes; panelists ingested the selected meals for 10 minutes, rinsed thoroughly with 50 ml of tap water, and the pH response was monitored for the remainder of a 2-hour period. In the second test series, the same procedures were followed through the post-meal ingestion rinse. After the pH response to the meal was monitored for 5 minutes, the panelists chewed a sorbitol gum for 15 minutes in their usual manner and the panelists were encouraged to move the gum around their mouth, however, it appeared as if they favored the side of their mouth without the partial denture. The pH response was monitored for the balance of the 2-hour period. All panelists ate the test foods, with and without the chewing gum, according to a randomized block test design. The results indicated that the use of sorbitol gum significantly raised the plaque pH, prevented the subsequent pH drops after the fast-food meal ingestion and reduced the pH curve area under 5.5. PMID- 2095802 TI - Incidence of hepatitis B exposure among USAF dental laboratory technicians. AB - The purpose of this study was to survey, serologically, the exposure history of USAF dental laboratory technicians to hepatitis B virus (HBV), and to compare the incidence to that found in the general military population. Blood samples from 145 technicians, with an average age of 26.9 (S.D. = 6.9) in four locations in the USA and Europe, were tested for the presence of HBV core antibody using a standard enzyme immunoassay (EIA) procedure. These results were compared against 397 military members in non-medical fields of equivalent age and rank. The binomially distributed data was converted to a z distribution and a statistically significant difference was found in a comparison of the probability of detecting anti-HBc in each population (P = 0.034) where the incidence among the technicians was 2.7% and the military population 0.76%. Use of a "barrier system" in the laboratory, and vaccinations, could prevent any increase in this incidence from an occupational source. PMID- 2095803 TI - Effectiveness of steam autoclaving on the contents of sharps containers. AB - The effectiveness of steam autoclaving on bacterial endospores placed within five types of sharps containers was tested. A variety of container physical orientations within the autoclave were evaluated. Spores were present on commercial spore strips or placed onto capped and uncapped dental needles. All strips and needles present in empty or filled containers could be sterilized within 15 minutes when the containers were placed on their sides and their vents left open. The contents of containers processed in an upward position required between 30-60 minutes of autoclaving before being sterilized. The size and shape of the containers influenced ease of sterilization. PMID- 2095804 TI - The effect of time on the adhesion of light-body to heavy-body Express in the two step reline polyvinylsiloxane impression technique. AB - Often times light-body wash (LB) cannot be added to the heavy-body putty (HB) within 30 minutes when utilizing the two-step reline impression technique. The purpose of this study was to add the LB to the HB at times greater than 30 minutes and test the tensile bond strength. A split aluminum mold which created a bonding area of 1.13 cm2 and tray were filled with Express HB. After HB set the Express LB in a tray was added at varying times. The split molds were then separated and samples tested on the Instron. Ten groups with five samples/group (determined by a pilot study) were made. The times which the LB was added to the set HB and tested were: A) Immediately (one-step procedure); B) 10 minutes and contaminated with saliva (negative control); C) 10 minutes; D) 30 minutes; E) 45 minutes; F) 1 hour; G) 3 hours; H) 24 hours; I) 115 hours; and J) Freshened after 3 months. The results of this study indicate that saliva-contaminated samples were weaker than all other groups (P less than or equal to 0.01) and as far as tensile bond strength between materials is concerned, there appears to be no detrimental effect in tensile bond strength between HB and LB when delaying the application of the light-body material (P less than or equal to 0.01). PMID- 2095805 TI - Extracted human versus bovine teeth in laboratory studies. AB - The purpose of this study was to determine the shear bond strengths and microleakage of Scotchbond 2/Silux to dentin and to evaluate resin penetration into the dentinal tubules of human and bovine teeth. The shear bond strengths (SBS) were determined on occlusal dentin of 25 human permanent molars (H) and on facial dentin of 25 bovine permanent mandibular incisors (B). The test specimens were stored in physiological saline at 37 degrees C for 24 hours prior to the application of a shear load in an Instron machine at a speed of 0.5 mm/min. Microleakage (ML) of Class V restorations placed on the facial surfaces of the roots of 15 human canines (H) and 15 bovine incisors (B) was determined quantitatively. The restored teeth were thermocycled x500 in 2% methylene blue solution, the dye extracted in 50% HNO3 and the dye concentrations determined spectrophotometrically. The resin penetration into the dentinal tubules was evaluated in the SEM. The following results were obtained: SBS (MPa): H, 6.2 +/- 2.9; B, 4.4 +/- 1.2; ML (microgram dye): H, 4.7 +/- 3.2; B, 15.9 +/- 10.5. The data were analyzed by t-test. The shear bond strength of Scotchbond 2/Silux to human dentin was significantly greater (P = 0.0096) and the microleakage significantly less (P = 0.0004) than to bovine dentin despite the fact that the restorative system penetrated more densely into bovine dentin. The use of bovine teeth instead of human teeth in these types of tests is not indicated. PMID- 2095806 TI - Polymeric adhesion to dentin: contrasting substrates. AB - Clinical research has shown that resin dentin adhesive materials often fail prematurely despite encouraging laboratory-derived data. Current adhesives are reported to react with dentin surfaces by chemical and/or micro-mechanical mechanisms. The ionic bonding to calcium and the covalent coupling to collagen are representative chemical strategies employed today. Recent findings suggest that the mechanical interlocking of resins into open dentinal tubules may play an even more important role with present adhesive systems. Dentin surfaces, such as cervical abrasions, undergo changes in the oral cavity and dentinal tubules may become partially or completely obturated by the growth of peritubular dentin or by the precipitation of mineral salts within the tubules. The resulting sclerotic dentin may be less receptive to current dentin adhesives. An examination of clinically aged dentin surface types revealed extreme variability in tubular morphology. The more sclerotic dentin presented, the less effective was dentin conditioning and resin adaptation. Early correlations with ongoing clinical trials appear to substantiate this finding with the greatest failure of restorations occurring in more sclerotic lesions. PMID- 2095807 TI - Laboratory study of the Herculite XR system. AB - The shear bond strengths of the Herculite XR system to dentin were determined the quantitative microleakage of Class V restorations in dentin evaluated; the fluoride release from the XR-Ionomer determined, and fractured test specimens depicting various failure patterns examined in the scanning electron microscope. The shear bond strength of the XR-Ionomer to dentin was 6.6 +/- 1.7 MPa and the Herculite XR 15.4 +/- 3.7 MPa. Sixteen of the 20 Herculite XR test specimens fractured in dentin. The quantitative microleakage of Class V Herculite XR restorations in dentin was 2.22 +/- 1.94 micrograms dye which was significantly reduced to 0.91 +/- 0.63 micrograms when the XR-Ionomer was placed in the floors of the preparations. The fluoride release from the XR-Ionomer dropped sharply during the first 6 days after which it reached a plateau at approximately 0.5 microgramsF.mm-2. PMID- 2095808 TI - Artificial root caries in amalgam restorations: effect of light-cured fluoride releasing liners. AB - The purpose of this study was to examine artificial root caries when light-cured fluoride releasing liners were placed under amalgam restorations. Class V preparations in extracted third molars were used with gingival margins on root surfaces. Ten restorations were used for each of the following groups: 1) Amalgam alone; 2) Two layers of copal varnish and amalgam; 3) Vitrabond, amalgam; 4) Timeline, amalgam; 5) XR Ionomer, amalgam. The teeth were thermocycled and artificial caries were created using a liquid system acidified to pH 4.20 containing 2.2 mM calcium and phosphate but without fluoride. The teeth were sectioned, polished and photographed using polarized light. Areas of recurrent caries were measured using a sonic digitizing pad. The data were analyzed using ANOVA and Duncan's Multiple Range Test. Areas for root lesions for the different groups were: 1) 2.17 +/- 0.35; 2) 1.90 +/- 0.40; 3) 1.30 +/- 0.18; 4) 1.77 +/- 0.28; 5) 1.50 +/- 0.33. Groups 3 and 5 were statistically different from groups 1 and 2, while no differences were observed for enamel lesions. The use of the photo-activated/fluoride releasing liners significantly reduced lesion area. PMID- 2095809 TI - A one-visit composite post-crown restoration: case report. AB - A prefabricated endodontic post was cemented with glass ionomer, then composite resin was used to build up a core and fabricate a crown restoration. This treatment has been successful through a 2-year observation period, and may represent a treatment alternative for certain clinical situations, in which traditional cast procedures are not acceptable to the patient. Further investigation is necessary to evaluate the longitudinal success of composite resin crowns. PMID- 2095810 TI - Reactivity toward cysteine of antimicrobial carbamimidothioic acid phenylalkylesters salts. AB - The rates of reaction toward cysteine of a series of carbamimidothioic acid phenylmethylesters halides were investigated in phosphate buffer pH 7.4 at 37 degrees C under pseudo-first-order conditions. The reaction involves nucleophilic attack of cysteine on the C-S bond of isothiouronium mojety and corresponding benzenemethanethiols were detected as product of the reaction. Apparent first order rate constants were determined. PMID- 2095811 TI - [Use of the "Sartorius" cutaneous absorption simulator for transdermal pharmaceutical forms of NSAIDs]. AB - We report the results of the in vitro-release of the active ingredients (flurbiprofen and ibuprofen) from dermal form obtained by the Sartorius Absorption simulator SM16750. The results show that the choice of the excipients is basic. Using NSAID, the aqueous gel can be considered the suitable formulation to obtained a good in vitro-release. The quantities of the active ingredients released during the time are plotted in diagrams. PMID- 2095812 TI - Effect of surfactants on diffusion of calcium in mucin: a possible mechanism affecting enamel remineralization. AB - By means of in vitro experiments, performed with a three compartment diffusion cell, we show how the presence of surfactants, often present in the formulation of dentifrices and mouthrinses, may affect the availability of calcium and its permeation rate through the proteic layer covering dental enamel (acquired pellicle). Mucin was the protein used to simulate the pellicle. Experiments were performed at different surfactant concentrations (i.s. below and above CMC) and also in the presence of fluoride ions that are capable of enhancing enamel remineralization. The mechanisms involved, mainly related to the interaction of surfactant monomers with the model protein, are discussed in this paper. PMID- 2095813 TI - Follow-up of methylmercury concentration in brain areas of developing rats exposed during prenatal life using cold-vapor absorption spectrometry. AB - The concentration and the distribution of mercury in six different brain areas of developing rats (21 and 60 days of age) exposed to methylmercury (MMC) during prenatal life were determined by using pressure decomposition of the tissues and cold-vapor atomic absorption spectrometry. The distribution of mercury in brain samples showed that the metal distributes to all brain areas, but with different levels. The amount of mercury in the brain areas was about 10-100 times higher, depending on the tested area, in MMC exposed rats than in control, at day 21 of age, while it was practically equal to controls at 60 days of age. These data seem to be of importance in order to correlate the presence of mercury in the brain and its distribution to brain areas after a single exposure to MMC with transient or permanent changes in specific neurotransmitter system and altered behaviors. PMID- 2095814 TI - [Survival of bone tissue in organotypic culture under intermittent mechanical loading. Preliminary results]. AB - With the aim to study the mechanism of transduction of mechanical stimuli in biological ones we have realized an experimental device for the application of intermittent mechanical forces on bone specimens in vitro. The scheme of the device is reported in Fig. 1. It is constituted by a drive shaft which rotates on eccentric axis (1) supporting a longitudinal bar (2) with the load (3). The latter rests on a piston (4) only during a limited period of every shaft revolution, so that the load becomes intermittent. The bone specimen (5) is placed under the piston and the two are placed in a tube containing the culture medium. This latter is BGJ mod. Fitton-Jackson (Gibco), enriched with fetal calf serum (10%) and ascorbic acid (70 microliters/ml). Right metatarsi from 18-day old rats were removed aseptically and placed under the piston for 2-6 days after resection of both ends. The homotypic ones, unloaded, were placed in 30 mm Petri dishes, and used as a control. The incubator environment was 5% CO2 in air (A group), or enriched with O2 (25-35%) (B group). At the end of the experimental period the bone specimens were fixed in 4% formalin buffered and treated for conventional histologic methods. In the A group most of the osteocytic lacunae were empty. The osteoblasts disappeared already at the 2nd day; the periosteal fibroblast dedifferentiated and multiplied. The deposition or calcification of osteoid were completely lacking. The application of mechanical load promoted deposition of granular degenerative material around the bone, and the periosteal cells, well differentiated, were surrounded by metachromatic material, which resembles cartilage matrix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095815 TI - Osteoclast bone resorption is enhanced in the presence of osteoblasts. AB - Bone resorption activity by osteoclasts has been evaluated in a co-culture system in which osteoclasts have been plated in the presence of osteoblasts. The system prevents cell-cell contact but permits diffusion of molecules through the pores of a millipore membrane that separates the two compartments in which the two cell types have been plated. Results demonstrated that osteoblasts exert a stimulatory effect over osteoclast bone resorption due to soluble molecules capable of passing through the membrane pores. The effect is specific since periosteal cells, which do not express osteoblastic characteristics, fail to induce changes in the osteoclast activity. PTH does not affect osteoblast-mediated enhancement of bone resorption, indicating that the stimulatory effect that the hormone exert in vivo occurs via a different cellular system. PMID- 2095816 TI - The role of protein kinase C in the osteoclast activity. AB - Isolated chicken osteoclasts in culture have been treated with 100 nM PMA for 20 minutes, and processed for the decoration of the microfilaments with fluorescent phalloidin. Results demonstrated that this phorbol ester, which activates the protein kinase C, induces the assembly of microfilaments in stress-fibers, and enlarges the microfilamentous core of podosomes. This results indicate that the protein kinase C mediates specific arrangement of microfilaments in osteoclasts. The substratum for protein kinase C-mediated phosphorylation is however still unknown. PMID- 2095817 TI - [Hematic infiltrates and the expression of HLA-DR antigens in naso-sinusoidal polyps of the fibrous type]. AB - In this study fibrous nasal polyps, obtained from four patients, were analyzed by means of immunocytochemical methods for the presence of interstitial hematic cell infiltrate and HLA-DR molecule expression. This histologic type accounted for 36.4% of nasal polyps studied. Our results demonstrated that cells belonging to monocyte-macrophage lineage were mainly detected within fibrous and edematous zones (greater than 50%), whereas T cells were found within the subepithelial peripheral connective tissue (greater than 60%). Surface and gland epithelial cells appeared to be more intensely stained for HLA-DR molecules than nasal epithelium of normal subjects, thus indicating that the intensity of HLA-DR molecule expression correlated with the presence of a hematic cell infiltrate. Nasal polyps are a frequent pathology whose etiology has not yet been completely clarified. The present study provides additional information about the fibrous polyp structure and can support some speculations on the nasal polyp etiology. PMID- 2095818 TI - [Pancreatic passenger leukocytes in organs obtained from cadaver donors for allotransplantation]. AB - In previous studies we have demonstrated that human normal pancreata were populated by interstitial mononuclear cells constituted by dendritic cells (70%), macrophages (30%) and few B cells (less than 1%). Furthermore, the endocrine parenchyma and the centroacinar cells appeared negative for the detection of HLA A,B,C molecules. In the present report, 15 pancreata from cadaver donors were studied by means of immunohistochemical methods. 5 out of 15 organs were found to contain a larger amount of interstitial hematic cells that were constituted mainly by macrophages and B cells, together with a small percentage of granulocytes and T cells. In such "infiltrated" pancreata both endocrine parenchyma and centroacinar cells displayed a positivity for HLA-A,B,C antigens. As HLA-class I antigens have importance in allo-recognition and rejection responses, our data suggest that pre-transplant biopsies may be useful for a better evaluation of the pancreatic tissue immunogenicity. PMID- 2095819 TI - [Social and behavioral organization of horses on the Giara (Sardinia): distribution and aggregation]. AB - In this paper some considerations on the environment of the 42 Kmq of the volcanic-basaltic Giara tableland are discussed. Conditioning by the environment and its effect on the distribution of a population of 712 horses is illustrated in view of their social and behavioural organization. PMID- 2095820 TI - [Administration of glutathione and lipid peroxidation induced during fasting]. AB - It is well known that lipid peroxidation may be initiated or exaggerated by conditions leading to hepatic GSH depletion or altered GSH/GSSG ratio. In our study we evaluated the effects of GSH administration on hepatic, bile and plasma GSH, GSSG and MDA in rats depleted of the tripeptide by a prolonged. fasting. An exteriorized biliary-duodenal fistula was established and GSH or saline solution was administered i.p. for a period of 6h. Rats treated with GSH exhibited an increased GSH and decreased GSSG biliary excretion. Whereas in control rats an opposite pattern was observed, namely enhanced GSSG and decreased GSH biliary excretion. While hepatic GSH and GSSG concentrations were comparable in the two groups, a significant increase in liver and plasma MDA production was found in controls compared to GSH treated rats. Our data suggest a protective role of GSH against the production of lipoperoxidation as evidenced by the decrease of hepatic, biliary and plasma MDA levels and by a decreased percentage of biliary GSSG. In addition, the significant increase of biliary GSH excretion, observed in rats treated with GSH compared to controls, may be due to an increased supply of the tripeptide which is known to be preferentially excreted into bile in the reduced form. PMID- 2095821 TI - Fetal antigens as tumor growth enhancing factors in Yoshida's tumor rats. AB - Malignant neoplastic cells have been shown to have some antigenic features identical to those of embryonic cells. Since several antigens are likely to be shared by both embryonic cells and neoplastic tissue, we tried to understand the meaning of the appearance of such antigens and the type of effect that the immunization with embryonic antigens would have on the survival of Yoshida's tumor rats. Wistar rats were immunized with fetal antigens by fetal cells (1.5 x 10(6)) suspended in 0.5 ml of Hanks solution plus an equal volume of Freund adjuvant, were injected in hind footpads, i.p. and i.m., respectively, for active immunization. Rabbit antigen sera were used for passive immunization. All animals presented ascites and tumor growth. Animals immunized by means of fetal cell antigens showed a mean survival rate after neoplastic transplant of 14 days. Animals that received rabbit immune serum showed a mean survival rate after neoplastic transplant of 17 days. The immunization by means of fetal antigens elicited a scanty effect on the survival of Yoshida's tumor transplanted rats. It can be concluded that antibodies, which are able to cross react with neoplastic cells, do not have cytotoxic effect and do not interfere with the survival of the neoplastic transplanted animals. Therefore, fetal antigens are likely able to carry out an immunosuppressive action. The fact that they appear on neoplastic cells could be seen as a metabolic modification effect or as a growth enhancing factor. PMID- 2095822 TI - [Adaptation of motor nerve fibers to physical activity]. AB - The effects induced by training on the H-reflex of soleus and lateral gastrocnemius muscles have been studied on 19 adult male volunteers; out of these, 10 were non-trained subjects and the remaining 9 were top level athletes engaged in sports requiring very rapid and intense contractions (sprinters and volley-ball players). It has been observed that the latency of the M response is significantly higher in the athletes than in the non-trained subjects. Instead, no significant differences were observed between these two groups, concerning the latency of H response. The increase of M response latency is likely due to a decrease of nerve conduction velocity in the terminal part of motor fibers. The possibility that this conduction speed decrease could be dependent on sprouting and/or terminal branching growth of the motor nerve ending is discussed. PMID- 2095823 TI - [Growth of the Yoshida ascites/hepatoma in co-culture with rat fibroblasts]. AB - Ascites hepatoma cells (Y) co-cultured with rat fibroblasts (F) in Dulbecco Eagle's MEM (DMEM) proliferate rapidly in suspension, at a rate consistent with that shown in vivo after intraperitoneal injection; the population doubling time is about 1 day. The log phase of growth may be retained indefinitely, provided fresh medium is supplied regularly and the F monolayer is changed when necessary. The tumorigenicity is preserved. To maintain a high rate of growth the presence of F seems important: in this study, culturing without F in various media at best only sustained slow proliferation rates; this is in keeping with the notion of normal tissue components supplying useful factors to the neoplastic cells. Adding minced polyester surgical thread (Mersilene - M) into the co-cultures slowed down the growth of Y to some extent, yet no evidence has been obtained of toxic compounds released by M. PMID- 2095824 TI - [Embryotoxicity of fenbendazole in Paracentrotus lividus]. AB - The aim of the present work was to evaluate the embryotoxicity of Fenbendazole, a benzimidazole carbamate-derived anthelmintic drug widely employed in Veterinary Medicine, by using the embryonal development of Paracentrotus lividus (sea urchin) as a experimental model. Embryos were obtained by in vitro eggs fertilization and cultured in seawater. Five embryo suspensions were added by Fenbendazole reaching a final concentration of 5 micrograms/l, 7.5 micrograms/l, 10 micrograms/l, 12.5 micrograms/l and 25 micrograms/l; a suspension was kept drug-free as a control. Embryo development was evaluated by microscopical examination of suspensions at 3 and 40 hours. Our results show that a concentration of 5 micrograms/l of the drug determines a considerable delay of the embryonal development in the 95 percent of the elements observed, and a concentration of 25 micrograms/l produces a block of the embryogenesis at the phase of morula and blastula in all embryos. Results confirm that the effects observed are probably due to an extended inhibition of several enzyme complexes of the embryo cells. PMID- 2095825 TI - Two unusual congenital anomalies of the tricuspid valve. AB - We describe two unusual congenital anomalies of the tricuspid valve discovered incidentally at autopsy. One is an abnormal attachment of the tricuspid septal leaflet to one of two posterior papillary muscles with a concomitant fusion of the right ventricular septal and anterior papillary muscles in a patient with ectodermal dysplasia. The other involves a fenestration defect of the septal leaflet of the tricuspid valve in a patient with aortic stenosis, coronary artery atherosclerosis, and cardiac amyloidosis. PMID- 2095826 TI - Neoplasms metastatic to the heart: review of 3314 consecutive autopsies. AB - Cardiac involvement by metastatic neoplasms is relatively uncommon and usually occurs with widely disseminated disease. Ninety-five cases with cardiac metastases from autopsies performed over a 14-year period (1974-1987) at Loyola University Medical Center are reviewed. During this period, 3314 autopsies were performed with an average annual autopsy rate of 35%. In 806 (24.3%), a malignant disease was found, and in 95 (11.8%), there was cardiac involvement by tumor. The most common malignancies encountered in order of decreasing frequency were lung, lymphoma, breast, leukemia, stomach, melanoma, liver, and colon. Although the percentage of cardiac metastasis compares favorably with previous reports in the literature, an identical rate was present during both halves of the 14-year period studied. Improved diagnostic capabilities and treatment protocols in recent years have apparently not significantly affected the incidence, distribution, or patterns of metastatic spread to the heart. PMID- 2095827 TI - Diagnostic endomyocardial biopsy findings in 160 consecutive patients: the Yugoslavian experience. AB - Percutaneous endomyocardial biopsy was performed for the diagnosis of various heart disorders in 160 consecutive patients in Belgrade, Yugoslavia. Tissue specimens were taken from the left ventricle in 150 patients and from the right ventricule in 10. To determine the clinical merit of endomyocardial biopsy, patients were divided into six groups based upon the existing clinical findings, including cardiomyopathy, myocarditis, specific heart muscle disease, alcohol induced heart disease, major dysrhythmias, and other diagnoses. The clinical value of endomyocardial biopsy was gauged by the number of diagnoses that were histologically confirmed by the procedure. We combined the percentages of histologically suspected clinical diagnoses with those of completely changed clinical diagnoses and found that endomyocardial biopsy provided useful information in 70.6% of cases. Nonspecific histological findings were found in 25.6% of cases. The biopsy proved to be of no clinical value in only 3.8% of the cases. Although some investigators still object to the overall clinical usefulness of diagnostic endomyocardial biopsy, our findings help to underscore the value of this procedure for making an accurate diagnosis. PMID- 2095829 TI - Inotropic interventions during myocardial "stunning" in the pig. AB - To study the effects of inotropic interventions on myocardial "stunning," we subjected pigs to 12 minutes of left anterior descendents (LAD) coronary artery occlusion followed by 2 hours of reperfusion. Measurements were made of segmental shortening (SS%), myocardial blood flow (MBF), adenine nucleotides, the extent of ultrastructural damage, and granulocyte accumulation. Three groups of pigs were compared: control (CON) (N = 6), isoproterenol infused (ISO) (N = 6), and pretreated with triiodothyronine (T3) (30 micrograms/kg ip) (N = 5). Inotropic reserve was tested with a bolus of Ca++. During reperfusion, SS% in the CON reperfused segments showed a relatively constant decrement of 75% throughout the reperfusion period but no alteration in the inotropic reserve. In the ISO group, SS% was maintained at preocclusion levels, but there was a small but significant decrease in the inotropic reserve. In the T3 group, SS% was reduced more than 90% and showed no response to the Ca++. Myocardial blood flow was maintained at control levels in the CON and ISO groups during reperfusion but was greatly reduced in the T3 group. The ATP was reduced 36% in CON, 39% in ISO, and further reduced to 87% of control in the T3 group. Mitochondrial damage in the CON and ISO groups was 5 and 10%, respectively, and reversible, but there was 86% irreversible damaged mitochondria in the T3 group. Using a monoclonal antibody against pig granulocytes, the presence and quantitation of adherent granulocytes were determined. There was no accumulation of granulocytes. These data suggest that some forms of myocardial adrenergic augmentation during stunning may have adverse consequences. Thus, the strength, duration, and types of stimulation may be critical to the preservation of the myocardium in the treatment of myocardial stunning. PMID- 2095828 TI - Reperfusion injury in ischemic myocardium: protective effect of controlled reperfusion. AB - Restoration of coronary artery flow following a period of ischemia often results in further ultrastructural damage to cardiac fibers, a phenomenon known as reperfusion injury. We have compared the ultrastructural effects of uncontrolled reperfusion in vivo of ischemic pig myocardium with the ultrastructural effects of reperfusion controlled at flow rates comparable to preischemia levels. Myocardial ischemia was produced for 60 minutes in 9 pigs by means of a reversible coronary artery occlusion, after which coronary artery flow was restored for 120 minutes. This restoration of flow was complete in four pigs (resulting in uncontrolled reperfusion) and partial in five pigs, with constant monitoring and adjustment of flow to maintain rates near preischemia values (controlled reperfusion). Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and ischemic depletion of glycogen were graded independently and blindly by two investigators using a simple, nonparametric three-point scale. Ischemic damage was greater in pigs receiving uncontrolled reperfusion than in animals receiving controlled reperfusion, and these differences were significant for ischemic effects on nuclei (p less than 0.01), glycogen (p less than 0.02), and myofibrils (p less than 0.05) but not for ischemic effects on mitochondria (p = 0.095). We conclude that uncontrolled, hyperemic flow during reperfusion of ischemic myocardium is responsible, in part, for the phenomenon of reperfusion injury. PMID- 2095830 TI - Inhibition of ectopic calcification of glutaraldehyde crosslinked collagen and collagenous tissues by a covalently bound diphosphonate (APD). AB - Calcification of collagen-derived prosthesis, such as glutaraldehyde crosslinked porcine heart valves or heart valves assembled out of bovine pericardium, presents a major clinical problem. Their subcutaneous implantation into young rats provides us with a reproducible method of assessing this form of ectopic calcification. Long-term implantation is essential, since some materials which do not calcify within the first month frequently exhibit a delayed calcific response. Crosslinked pericardium is much more likely to calcify than crosslinked tendon or reconstituted crosslinked pepsin extracted bovine type I collagen. The covalent binding of a diphosphonate to collagen and collagen-rich tissues can prevent calcification. The binding of this diphosphonate and its ability to inhibit calcification can be enhanced by increasing the number of amino groups on the collagen molecule. The degree of calcification is inversely related to the number of diphosphonate molecules covalently bound to collagen. Under standard conditions, chemical modifications appear to occur primarily on the surface of the collagen fibrils, as evidenced by the relationship between the number of molecules of APD bound and fibril diameter. The bound diphosphonate seems to interfere with crystal growth and prevent the formation of highly insoluble hydroxyapatite on the surface and interstices of the collagen fibrils. PMID- 2095831 TI - Microvasculature sparing with controlled reperfusion of ischemic myocardium. AB - Reperfusion of ischemic myocardium may result in further ultrastructural damage to cardiac fibers, a phenomenon known as reperfusion injury. We have recently shown that controlled reperfusion, with maintenance of reperfusion flow rates near preischemia levels, prevents much of this reperfusion damage. This observation suggests that mechanical damage to the myocardial microvasculature is important in the pathogenesis of reperfusion injury. In this study, we have used electron microscopy to examine the microcirculation of ischemic, reperfused pig myocardium under conditions of uncontrolled and controlled reperfusion. Animals receiving uncontrolled reperfusion (reperfusion flow 3-4 times preischemia levels) showed ultrastructural damage to myocardial capillaries after 1 hour of ischemia and 2 hours of reperfusion. This damage was manifested as depletion of endothelial cell pinocytotic vesicles, plugging of capillaries by erythrocytes, leukocytes, and fibrin-containing microthrombi, and perivascular microhemorrhages. None of these changes were found in animals receiving controlled coronary artery reperfusion. We conclude that mechanical damage to the myocardial microvasculature is important in the pathogenesis of reperfusion injury and that such damage is obviated under conditions of controlled coronary artery flow during reperfusion. PMID- 2095832 TI - Liposarcoma of the heart. A case report. AB - The authors report a tumor of the heart in a 33-year-old man. Preoperative diagnosis was of a cardiac myxoma. Upon operation, the tumor was revealed to arise from the right atrial free wall, occupying most of the atrial and ventricular cavities and causing a noticeable enlargement and obstruction of the tricuspid valve as well as the mentioned cardiac chambers. A smaller part of the tumor was placed on the outside of the right atrial wall, and implants of the tumor in the distal part of the aorta, extending backward to the bifurcation of the pulmonary artery and its branches, were also observed. Histological examination showed a myxoid-type tumor with light and ultrastructural features of liposarcoma. The patient died 13 months after surgery with regional extension of the tumor. PMID- 2095833 TI - Assessment of neuron in congenital heart disease with heart failure. AB - Pathological studies in five hearts from patients with congenital heart diseases have demonstrated that the number of neurons is similar to that found in normal controls. The number of neurons has been counted in a strip of right atrial wall between the venae cavae. The hearts were selected from a wide spectrum of the population, the youngest being 5-months old and the oldest 35 years old (mean age: 12 years); all were in failure. The neuronal counts are comparable to those found in a normal population of mean age 40 years. PMID- 2095834 TI - Dissecting aneurysm of a coronary artery due to percutaneous transluminal balloon angioplasty. AB - Percutaneous transluminal balloon angioplasty (PTCA) is utilized successfully to dilate stenotic coronary arteries. The procedure is a frequent nonsurgical method to restore coronary artery blood flow to ischemic myocardium. In this paper, we report a case of intimal tear and medial dissection of the right coronary artery leading to a dissecting aneurysm and occlusion of the coronary artery. The patient died following coronary artery bypass grafts, and the autopsy demonstrated the dissecting aneurysm of the coronary artery. PMID- 2095835 TI - Aspergillus terreus myocarditis: report of a case and review of the literature. AB - Aspergillus terreus is an uncommon cause of myocarditis, with only six reported cases in the world literature. This report describes a case of severe disseminated Aspergillus terreus infection with extensive involvement of the heart in an immunosuppressed patient after aortic valve replacement surgery. Pathologic findings are similar to those found in Aspergillus fumigatus myocarditis. All six previously reported cases of A. terreus carditis occurred in postoperative cardiac surgery or immunocompromised patients. This pathogen should not be dismissed as simply a colonizing organism or a contaminant in fungal cultures, particularly those from hospitalized or seriously ill patients. PMID- 2095836 TI - Developing intelligible signs with learning-disabled students: a review of the literature and an assessment procedure. AB - The use of sign language as an augmentative medium of communication is a well established approach in working with client groups who are handicapped in their effective use of verbal language. However, students with physical and learning disabilities may continue to experience problems in making themselves understood, because of inaccuracies in sign production which may be considered as analogous to phonological errors in speech. It is suggested in this paper that the evaluation and remediation of sign production errors is most usefully approached through an understanding of the phonological structure of sign language. The paper presents a review of the literature concerning the development of (1) motor patterns involved in sign production, and (2) the four major parameters of handshape, location, movement and orientation, in hearing-impaired and hearing children whose first language is sign, and in students with mental handicaps. A framework for assessing and monitoring sign production is suggested, and possible approaches to the development of intelligible signing are discussed. It is argued that the analysis and remediation of sign errors should always be related to the communication needs of the individual, rather than developed in isolation. PMID- 2095837 TI - Augmentative communication systems taught to cerebral palsied children--a longitudinal study. I. The acquisition of signs and symbols, and syntactic aspects of their use over time. AB - A longitudinal study of augmentative communication training with 40 language impaired, cerebral palsied children examined the acquisition of Blissymbols and Makaton Vocabulary signs and syntactic aspects of their use over an 18-month period. The children made measurable gains in these areas over time, but progress was very slow and they continued to show severe limitations in the repertoires of signs/symbols they acquired and in the average number, length and complexity of utterances they produced in semi-structured conversational settings. Possible reasons for these findings are discussed with reference to subject and system characteristics, and the teaching practices adopted in the schools. Comparisons between the Bliss and signing groups suggest that neither augmentative system facilitated greater progress in sign/symbol acquisition and use than the other. However, there was wide variability in performance among the children within each group. PMID- 2095838 TI - Coordination of sucking, swallowing and breathing in the newborn: its relationship to infant feeding and normal development. AB - Non-invasive, sensitive equipment was designed to record nasal air flow, the timing and volume of milk flow, intraoral pressure and swallowing in normal full term newborn babies artificially fed under strictly controlled conditions. Synchronous recordings of these events are presented in chart form. Interpretation of the charts, with the aid of applied anatomy, suggests an hypothesis of the probable sequence of events during an ideal feeding cycle under the test conditions. This emphasises the importance of complete coordination between breathing, sucking and swallowing. The feeding respiratory pattern and its relationship to the other events was different from the non-nutritive respiratory pattern. The complexity of the coordinated patterns, the small bolus size which influenced the respiratory pattern, together with the coordination of all these events when milk was present in the mouth, emphasise the importance of the sensory mechanisms. The discussion considers (1) the relationship between these results, those reported by other workers under other feeding conditions and the author's (WGS) clinical experience, (2) factors which appear to be essential to permit conventional bottle feeding and (3) the importance of the coordination between the muscles of articulation, by which babies obtain their nourishment in relation to normal development and maturation. PMID- 2095839 TI - Lingual activity in two speech-disordered children's attempts to produce velar and alveolar stop consonants: evidence from electropalatographic (EPG) data. AB - Research is accumulating to suggest that, in the process of phonological acquisition, children pass through a stage of producing subphonemic acoustic cues to distinguish target phonemic contrasts. These subtle, or covert, distinctions occur unnoticed by a transcriber, yet their existence is viewed as having potentially important theoretical and clinical implications. In this study, the technique of electropalatography (EPG) was used to investigate tongue placement in two speech-impaired subjects (sisters), during their attempts to produce alveolar/velar stop contrasts, and their EPG printouts compared to those of a normal subject. Transcription of the impaired subjects' speech showed that, whilst one was able overtly to produce the contrast, the other was using the phonological process of alveolar backing, and so was judged not to have the contrast. However, contrary to the predictions made based on the auditory transcription, the EPG data revealed that both children were making similar, and clearly distinguishable, lingual-palate contacts for the two places of articulation. Examination of the data revealed that the subject who was overtly producing the contrast was able to control the precise sequence of tongue movements necessary in the release phase of the two classes of stops. This critical stage in alveolar/velar stop production had not been mastered by the subject who was not producing a perceptible distinction. The clinical relevance of these findings is discussed. PMID- 2095840 TI - Training counterparts in cleft palate speech therapy in the less developed world: an extended report. AB - This paper describes the training of five counterparts in cleft palate speech therapy which took place in Sri Lanka. The context in which this training occurred is described. The original aims of the training, and criteria drawn up for the selection of the counterparts, are contrasted with the modifications required to these once the British therapists started working in Sri Lanka. Information is given on the training objectives, syllabus, curriculum and methods of evaluation of the counterparts' progress. The achievements of the counterparts are described, and factors relating to the difficulties and ease with which the counterparts were trained are discussed. The paper concludes with a discussion of the cultural, political and clinical problems encountered in this type of training, and highlights the special difficulties encountered in the training of counterparts in the field of speech therapy in less developed countries. PMID- 2095841 TI - Figurative language and reading comprehension in American deaf and hard-of hearing children: textual interactions. AB - The limited evidence on figurative language in deaf children, as well as 'professional intuitions', has led those who teach them to conclude that reading comprehension will be significantly complicated by figurative language. However, there are disagreements among practitioners as to how best to manage figurative language when it appears in text. Generally, some sort of textual modification is made, although those for and against 'simplified texts' are split on this issue. Those who favour them suggest either that complex vocabulary and syntax be reconstructed or that they be gradually introduced. However, reformulations are seldom standard nor are the figurative tropes such as metaphor, simile, personification etc. systematically introduced. Those against simplified texts argue that the problem of figurative language control is not one of linguistic complexity, but one of cognitive processing: deaf children can grasp inferred or indirect meaning so long as the referential domain is made clear. Such comprehension comes by way of demonstration, practice and feedback and figurative language need not present a special problem. In this present study, 14 deaf and hard-of-hearing children and youths who had been randomly assigned to one of two groups were given an original story entitled 'Peaches the Cat' and asked to read it. One group read a literal version of the story and one group read a figurative version in which all textual answers to the question were masked with figurative phraseology. Both groups answered the questions above a chance level and the figurative version did not prove to be more difficult than the literal version. The two groups were comparable on hearing loss and on reading and language ability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2095842 TI - [Diagnostic nucleic acid hybridizations for infectious diseases]. AB - The use of nucleic acid hybridization techniques has expanded into many areas, including studies of gene structure and function, routine diagnosis of human, animal and plant diseases, and also forensic science. In situ hybridization is one of the techniques currently available for nucleic acid hybridization and has some distinct advantages compared with standard techniques such as dot-blot, Southern or Northern hybridization, in which the histological structure is lost during extraction of nucleic acids. On the other hand, immunohistochemical staining is one branch of histochemistry that has received considerable attention in recent years as a very sensitive method for localization of specific proteins and other antigenic macromolecules within tissues and cells. This technique has also been widely used for clinical diagnosis and in various fields of research in medical science and biology. Automation of colorimetric in situ hybridization and immunohistochemistry would greatly contribute to the ease of introducing these techniques for routine pathological diagnosis and would improve the reproducibility of the assay. In this review, author will describe the development of an automated method for in situ hybridization and immunohistochemical staining using an automatic machine for both procedures. PMID- 2095843 TI - [Molecular basis of organic acidemia--propionic acidemia]. AB - Propionic acidemia is an inborn error of organic acid metabolism caused by deficiency of propionyl-CoA carboxylase (PCC: E. C. 6. 4. 1. 3.). We have detected three types of mutation in the same exon of the coding sequence of beta subunit of PCC (beta PCC) from two ethnic background (Caucasians and Japanese): an insertion/deletion which replaces 14 nucleotides with 12 unrelated nucleotides results in the elimination of an Msp I site; a 3-bp inframe deletion results in loss of one of two consecutive isoleucine codons immediately preceding the same Msp I site; the C----T transition results a in loss of the same Msp I site. The insertion/deletion and the C----T transition show high allele frequency in Caucasians (0.32) and in Japanese (0.3), respectively. These results reveal the possibility of the independent origin of the mutation in the two ethnic backgrounds and suggest a key role of this exon in the structure and catalytic function of the beta-subunit of PCC. PMID- 2095844 TI - [Towards cloning the gene responsible for myotonic dystrophy]. AB - For the purpose of cloning the gene of myotonic dystrophy (DM) using the technique of reverse genetics, we have introduced new methods such as microdissection, a YAC library and a Not I linking library and cloned many DNA fragments derived from the region of 19q13.2. Then we have assigned these to chromosome 19 by linkage map (CEPH families and linkage disequilibrium) and physical map (PFGE and in situ hybridization). Here we have described these methods. PMID- 2095845 TI - Possible involvement of bone cells in a new cementum formation. AB - Cells from the gingival lamina propria, bone-derived granular tissues and periodontal ligament (PDL) were isolated after periodontal surgery and subsequently cultured in vitro. The resulting cells were defined as gingival cells, bone cells and PDL cells, respectively. Under a phase contrast microscope, the cultured cells exhibited a spindle and/or a polyhedral shape. On the basis of their appearance under an electron microscope, spindle-shaped cells and polyhedral-shaped cells were identified as fibroblasts and osteoblasts, respectively. Bone cells, a homogeneous population of osteoblasts, had a more rapid growth ability than PDL cells, which were a heterogeneous population of fibroblasts and osteoblasts. Of particular interest was that only bone cells produced bone matrix in the multilayers in vitro. These results support the hypothesis that the phenotype expressed by cells from the alveolar bone establishes a new concept for progenitor cells in the formation of cementum. PMID- 2095846 TI - [Establishment and characterization of a human cell line, HS-MM, derived from a case of clear cell sarcoma]. AB - The characteristics of a new human clear cell sarcoma (CCSa) cell line, HS-MM, established from the pleural effusion in a 39-year-old man with lung metastasis, have been morphologically studied in vitro and in vivo. HS-MM cells growing on a cover-slip were round or spindle in shape with round nuclei containing extremely prominent nucleoli. Heterotransplantation of the cells into nude mice was easily succeeded following tumor development. Light microscopically, HS-MM cells, both in vitro and in vivo, were positive for anti-S-100 protein and anti-melanoma specific antibodies with immunostain, but no melanin pigment was detected in them. Ultrastructurally, the cells had round euchromatin-rich nuclei with large nucleoli revealing conspicuous nucleolonema, and contained a few mitochondria, rough endoplasmic reticulum and lysosomal dense bodies, besides a large amount of glycogen, but no melanosome in their cytoplasm. HS-MM cells retained and fully expressed morphologically unique characteristics as a CCSa, compatible with amelanotic type of malignant melanoma also. This cell line, HS-MM, therefore, proves to be extremely useful for clinicopathological studies on a CCSa. PMID- 2095849 TI - [AIDS and its manifestations in gingival and periodontal tissue]. AB - In 1981 AIDS acquired a lot importance, observing opportunist infections, not common malignant lesion and abnormalities in the immune system which develops in mysterious ways in healthy persons apparently or without pathologic background. The medical and scientific community respond immediately with intensive research to find the cause, prevention and treatment. The Journal American Medical Society is one of the principal sources to inform about AIDS. PMID- 2095848 TI - [Scaling and root hypersensitivity]. PMID- 2095847 TI - [Principles of periodontal therapy]. AB - In this work of adaptation and compilation, periodontal treatment phases and planning are suggested. Periodontal disease and its current classification are explained, It will be shown the factors that can modify the active therapy results as well as supportive therapy. PMID- 2095851 TI - [Gingivitis and periodontitis. Review and current concepts]. PMID- 2095850 TI - [Chemical agents for plaque control]. PMID- 2095852 TI - [Glossary of periodontal terms]. PMID- 2095853 TI - Genomic instability: a challenge for aging research. PMID- 2095854 TI - DNA sequence changes in aging: how frequent, how important? PMID- 2095855 TI - Present state and future development of the therapy of Alzheimer disease. PMID- 2095856 TI - The influence of aging and attentional demands on recovery from postural instability. AB - It is well known that the risk of a debilitating injury from a fall is much higher for elderly than for young individuals. In addition, it is well documented that healthy elderly subjects exhibit increased postural sway during normal stance tasks. In the present experiment, we explored the notion that control of minor postural instability in elderly subjects is attention demanding. Postural sway of eight elderly (mean age = 70.0 years) and eight young (mean age = 20.0 years) subjects was measured under two different secondary demands during stable and mildly unstable upright stance. There were two types of work loads. Either a cognitive (math task) or motor (hand-squeeze) task was performed during the second segment of a 50-second standing trial. The effect of these work loads on mean velocity, range, and variability of range of center of foot pressure was measured during the destabilizing activity of arm swinging and subsequent recovery period. Following seven seconds of 1 Hz arm-swinging activity, elderly subjects showed a marked increase in recovery time to normal stance when concurrently performing an arithmetic task. This result suggests that recovery from a posturally destabilizing activity, involving proprioceptive and vestibular information, places increased attentional demands on the postural support system of the elderly. PMID- 2095857 TI - Staff interaction with vocally disruptive demented patients compared with demented controls. AB - This study addressed the effect of social isolation on vocally disruptive demented patients (V); the results center on the amount of time patients spent in interactions, and the differences in type and time of staff-patient interaction (IA), compared to controls (C). Semi-structured observations were collected (1100 hours) for 37 vocally disruptive patients and 37 controls, all residents of psychogeriatric wards. Quantitative analysis revealed a low frequency of interactions, elicited mainly for procedural matters and short duration of most interaction episodes. Multiple regression analysis showed a significant difference in the type of interaction: there was more correction of undesired behaviour for vocally disruptive patients than for controls. The results show that social isolation is part of the institutionalized demented patients' life. The dominance of short interaction episodes could contribute to overstimulation. The only significant difference found was the frequency of corrective interactions in the group of vocally disruptive patients. We conclude that this is not the cause of their behaviour, but it may reinforce it. Other factors that might cause and maintain this behaviour require investigation. PMID- 2095858 TI - Neuroendocrine markers in aging brain: clinical and neurobiological significance of dexamethasone suppression test. AB - The dexamethasone suppression test (DST) is commonly accepted as an indicator of hypothalamus-pituitary-adrenal (HPA) axis functioning in clinical practice. In this study, DST was carried out in a geriatric population composed of patients with dementia of Alzheimer type (DAT), stroke and age-matched controls. The stress state of the subjects was also functionally assessed by the Symptoms Rating Test (SRT). The results disclosed no significant differences in basal cortisol levels in the three groups. A positive correlation between age and log transformed basal cortisol levels was found in the entire population as well as in each group. After dexamethasone administration, 20% of controls, 49% of DAT patients, and 48% of stroke patients were non-suppressors. At 8.00 a.m. and 11.00 p.m. after dexamethasone, cortisol levels were significantly lower (p less than 0.02) in controls than in pathological groups. A significant positive correlation between age and symptoms of depression and anxiety was found. One-third of stroke patients showing lesions in the right hemisphere were non-suppressors, and presented mostly subcortical infarcts, while 1/4 of them had depressive disorders. This study demonstrated a progressive increase in basal cortisol levels and depressive symptoms with age, a poor diagnostic value of DST in age related pathological conditions such as DAT and stroke, and the role of these cerebral pathologies in amplifying the neuroendocrine dysregulation due to the ageing process itself. DST is a useful biological marker for disclosing the vulnerability of the ageing brain, but it has no diagnostic value. PMID- 2095859 TI - Subjective well-being and its domains across different age groups: an Israeli sample. AB - Subjective well-being (SWB) across the life span was studied in a representative Israeli sample by a national survey of 1183 subjects, ranging from 18 to 80 years of age. Subjects were given "life scales", on which they rated their SWB in their present life, as well as their satisfaction regarding health, relations with friends, family, work, economic status, sense of personal achievement, and sense of control. The results indicate that: (a) SWB is negatively correlated with chronological age; (b) the relative strength of most of SWB domains changes in the different age groups; (c) SWB is best explained by different sets of domains in different age groups; and (d) economic status is the strongest domain, accounting for SWB in 6 out of 8 age groups. Explanations for these results confronted the developmental view of changing tasks across the life span vs cohort-based differences between the age groups. The decreasing number of domains that account for SWB variance with progressing age, as well as some unexpected findings with regard to the oldest age group (71-80) are also discussed. PMID- 2095860 TI - Domestic activities and walking in the elderly: evaluation from a 30-hour heart rate recording. AB - The physical activity pattern among 43 subjects (25 women, 18 men) from the Intervention Study of Elderly in Gothenburg (IVEG) has been evaluated by means of heart rate monitoring, rating of perceived exertion and recording activities over a 30-hour period. These subjects had previously been interviewed about their activity pattern, including the duration of their daily walks. In 91% of the participants the average heart rate was below 100 beats/min during walking. Considerable individual variations were noted in the duration of domestic activities and of walks. Using heart rate levels equal to or above the average heart rate during walking as a criterion, it was found that 68% of the women, but only 17% of the men, spent more time on domestic activities than on walking. Nonetheless, it is suggested that in addition to walking, domestic activities, owing to their duration, are important in maintaining physical fitness in the elderly, especially among women. This should be taken into account when physical activity is being classified (to avoid bias in favour of men). A modified version of a previously published six-grade scale for the classification of physical activity has been suggested. PMID- 2095861 TI - Establishing and implementing the goals of a registry for dementing diseases. PMID- 2095862 TI - Establishing diagnostic criteria for a registry for dementing diseases. PMID- 2095863 TI - New data gathering, instrument selection, and evaluation of existing information for determining entry. PMID- 2095864 TI - Data base management for a registry of dementing diseases. PMID- 2095865 TI - [A mechanism for setting a single rhythm for a multipacemaker sinoatrial node]. AB - Interaction of the system of n pacemaker cells modelling the work of the heart sinoatrial node was studied. Suggesting the interaction additivity an expression was obtained for the system single rhythm. Dependence of the system single rhythm and propagation velocity of excitation delay on the number of pacemakers of the leading centre and connection force between the pacemakers was investigated. The results obtained qualitatively, agree with the experimental evidence available. PMID- 2095866 TI - [Modelling the wave movement of a multisegment biomechanical system]. AB - Modeling of wave motion of human body's multi-segment biomechanical system by examination of forced transverse oscillations of one-dimensional bar system with distributed parameters is performed in javelin throwing. Energy flow value under different changes of model parameters is investigated. The experimental data showing wave front motion and transformation of spectral density of oscillations from segment to segment of the thrower's body are discussed. Share of the energy transferred along the body's segments in the total energy of javelin release is 70-72 per cent according to theoretical estimates for concrete model parameters, and 63-75 per cent according to the experimental data for 8 attempts. PMID- 2095867 TI - [Membrane bound hemoglobin]. PMID- 2095868 TI - [The connection of the electronic structure and biological activity of various derivatives of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine]. AB - Electron structure of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and some of its analogs--the substrates of monoaminooxidase--substituted by phenyl cycles was studied by semiempiric quantum-chemical CNDOR, MINDOB methods. The relationship between the obtained electron and conformation parameters (orientation of the phenyl ring in particular) and biological activity of the compounds under consideration is discussed. A comparative analysis of the distribution pattern of the electron density for the MPTP molecule calculated by the above methods showed a good agreement between the results obtained. PMID- 2095869 TI - [A chlorotetracycline fluorescent probe--an indicator of calcium ion binding with calcium-binding proteins]. AB - It has been found in in vitro experiments that fluorescence intensity of deionized solution containing a chlorotetracycline fluorescent probe increases insignificantly at the addition of calmodulin of S-100 proteins. Subsequent introduction of Ca2+ into the medium results in the pronounced fluorescence increase depending on Ca2+ concentration. Addition of specific protein blockers- W7 (calmodulin inhibitor) and antibodies to S-100 brought about a decrease of fluorescence. In in vivo experiments on chlorotetracycline-stained neurons of Helix Pomatia ganglia subesophageal complex it has been shown that bringing of antibodies to S-100 and calmodulin significantly decreases the fluorescence intensity of these cells. These data suggest that the chlorotetracycline probe is an indicator of calcium ions binding with calcium-binding proteins both in in vitro and in vivo systems. PMID- 2095870 TI - [Fluorescence studies of changes in methemoglobin structure during interaction with liposomes]. AB - Using fluorescence quenching technique the influence of phospholipids on methemoglobin conformation was investigated. The interaction of methemoglobin with model phospholipid membranes was shown to be followed by changes of protein structure-dynamic organization. PMID- 2095871 TI - [Thermodynamic parameters of fibril formation activation of evolutionary differentiated collagens]. AB - Activation parameters of fibril formation of evolutionary differing collagens were investigated. It has been shown that in a heated solution formation of collagen fibrils of different origin proceeds in different temperature regions related with the environmental temperature of species range. Enthalpy and free energy of the activation of fibril formation were measured. The data obtained show that fibril formation is preceded by the conformation of the molecules. Biological significance of the correspondence between the temperature of denaturation and that of the species range is discussed. The above correspondence is the limiting expression of functional dependence of conformational flexibility on temperature. Directed selection realized in the course of evolution is required for maintaining the velocity of collagen synthesis at the constant level. PMID- 2095872 TI - [A kinetic model of stationary calcium metabolism in smooth muscle cells]. AB - A model is proposed for Ca2+ stationary exchange in the myometrium cells in the absence of effects activating calcium channels of the plasmic membrane. The results of the model analysis point to an important role of the calcium pump (but not on Na(+)-Ca2+ exchanger) of the sarcolemma in providing the long-term regulation of physiologically significant concentration of ionized calcium in the smooth muscle cells. Ability of the calcium pump to efficiently compensate Ca2+ basal current continuously entering the myocytes at rest is proved. It is suggested that the stationary transsarcolemmal exchange of calcium (the system "basal calcium current--ATP-dependent transfer of Ca2+") underlies the control mechanism of the myometrium basal tonus, while a disturbance of the stationary state (with the pump inhibition) provides activation of the smooth muscle tonic contraction. PMID- 2095873 TI - [A community model of mutually learning neuronal nets]. AB - A model of a community is suggested whose members are formal neuron nets interacting by signals exchange. As a signal each net can emit an image formed by it when recognising the preceding signal. The emitted signal comes to the inputs of other nets and is used as their initial state for the recognition process. The collective dynamics of such model is discussed for the case of non-learning nets. Possible algorithm of mutual learning of the nets in them course of signals exchange is considered. PMID- 2095874 TI - [Photooptic response of blood plasma to low intensity red light]. AB - Photooptical response, both of the whole blood and of its non-pigmented fraction plasma to the low-intensity red light is investigated. For the case of the blood irradiation in vitro it is shown that the mechanism of the low-intensity red light effect on the blood is not directly associated with the pigmented molecular complexes concentrated in erythrocytes. Thus the effect of the low-intensity red light on living organisms includes the mechanisms not using light absorption by the specialized macromolecule--photoreceptor as a primary photophysical action. PMID- 2095875 TI - Cellular and molecular studies in brain and nervous system oncology. PMID- 2095876 TI - Chemotherapy for malignant brain tumors. PMID- 2095877 TI - Recent advances in neurosurgery. PMID- 2095878 TI - Recent studies on neurotoxicity and on the epidemiology of brain and nervous system tumors. PMID- 2095880 TI - Advances in the diagnosis and imaging of gastrointestinal cancer. PMID- 2095879 TI - Tissue tumor markers in the gastrointestinal tract. PMID- 2095881 TI - Recent developments in colorectal cancer epidemiology and early detection. PMID- 2095882 TI - Advances in the medical management of advanced gastrointestinal cancers. PMID- 2095883 TI - Advances in molecular biology and chemical carcinogenesis. PMID- 2095884 TI - Brain and nervous system. PMID- 2095885 TI - Gastrointestinal tract. PMID- 2095886 TI - Cytogenetics in malignant lymphomas. PMID- 2095887 TI - Diagnosis and staging of Hodgkin's disease. PMID- 2095888 TI - Advances in the treatment of lymphoma. PMID- 2095889 TI - Prognostic factors in non-Hodgkin's lymphoma. PMID- 2095890 TI - Laser and surgical therapy in gynecologic oncology. PMID- 2095891 TI - Chemotherapy, hormonal therapy, and steroid receptors in gynecologic cancer. PMID- 2095892 TI - Radiation therapy for gynecologic cancer. PMID- 2095894 TI - Chemotherapy-induced nausea and vomiting. PMID- 2095893 TI - Immunotherapy for ovarian cancer. PMID- 2095895 TI - Psychologic support and psychotropic medications. PMID- 2095896 TI - Lymphoma. PMID- 2095897 TI - Gynecologic oncology. PMID- 2095898 TI - [Use outside the hospital of 3d generation cephalosporins. Expert Group of the Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica]. PMID- 2095899 TI - [Pattern of antibodies in acute human brucellosis defined by Western blotting]. AB - We have evaluated with Western blotting the serologic response of 144 patients with acute brucellosis and 62 healthy controls to identify a useful antibody pattern to confirm the diagnosis of acute brucellosis. The antigen that we used was a protein extract of whole cells of the strain 115 (rough) of B. melitensis. Patients sera were obtained at the time of diagnosis and before the start of specific therapy. There was antibody response to 21 protein bands. The molecular weights (MW) and frequencies of the most significant bands were the following: 85 Kd (60.4%), 70 Kd (54.1%), 53 Kd (63.9%), 50 Kd (65.3%), 47 Kd (71.5%), 41 Kd (74.3%), 38 Kd (68.7%), 33 Kd (56.2%), 28 Kd (52.8%). At the time of diagnosis, 90.3% of the patients with acute brucellosis had antibody response to 2 or more protein bands of Mw of 47 Kd, 41 Kd, 38 Kd and 33 Kd. In none of the 62 negative control sera there was a response to more than one of the mentioned bands. PMID- 2095900 TI - [Evaluation of the bone marrow in patients with brucellosis. Clinico-pathological correlation]. AB - In the present study the 60 patients with brucellosis and evaluation of bone marrow aspirate seen at the Hospital Base Cayetano Heredia from 1980 to 1986 were included. Iron deficiency was found in the bone marrow in 34.5% of patients, 31% in males and 36% in females. No correlation was found between iron deficiency and severity of the hematological or non-hematological clinical features. Bone marrow cytophagocytosis was found in 28.3% of patients. All had moderate to severe clinical features, and it is postulated that this finding may be helpful as a severity marker in patients with brucellosis. Bone marrow cytophagocytosis was significantly associated with the presence of hematologic abnormalities in general; anemia was the most common of these, followed by thrombocytopenia. This finding suggests that cytophagocytosis is an important mechanism in the pathogenesis of these abnormalities in brucellosis. Bone marrow hypercellularity was present in 70% with normocellularity in 28.3% and one case of pure megakaryocytic aplasia. In thirty-five patients pathological study of bone marrow was carried out 10 of these (28.5%) had granulomas. Their presence was not correlated with the clinical severity. Peripheral blood finding were: anemia in 83.3%, with two cases of hemolytic anemia and positive direct Coombs test, one of them associated with thrombocytopenia (Evans syndrome); leukopenia in 21%, basically due to neutropenia; thrombocytopenia in 33.3%, in one case associated with positive antiplatelet antibodies and with pure megakaryocytic aplasia in others; pancytopenia in 13.5% of cases (8 patients) associated to bone marrow cytophagocytosis in 5 cases (64.5%) and thus suggesting that this might be the major underlying pathogenetic mechanism. PMID- 2095901 TI - [Malaria. Analysis of 149 cases (1981-1987)]. AB - The epidemiological features of the 149 cases of malaria reported to the Institut Municipal de la Salut in Barcelona from 1981 to 1987 are reported. The yearly evolution of the number of cases showed a tendency to increase predominating in the summer months. The incidence rate for 1977 was 1.99/100,000. The districts with the highest rate of involvement were districts I (Ciutat Vella), owing to the immigration, and V (Sarria-Sant Gervasi), probably owing to overseas visitors. There was a remarkable predominance of males (63.8%), patients aged 20 40 years, and cases of African origin (81.81%); 50.42% of these came from Equatorial Guinea. The most commonly isolated plasmodium was P. falciparum (52.53%), with a progressive increase throughout the years. Only 13.43% of patients had followed a correct chemoprophylaxis. Malaria is still the most important protozoan infection in the world. In the present study its possible reintroduction in Spain is discussed. The malarial endemic used to be very important in this country, and its eradication was not achieved until 1964. PMID- 2095902 TI - [Reflex sympathetic dystrophy. A new manifestation of Lyme disease?]. AB - Several syndromes derived from the involvement of central and peripheral nervous system and meninges have been reported in the infection by Borrelia burgdorferi. The features of autonomic nervous system involvement have received a marginal attention. Reflex sympathetic dystrophy is an autonomic picture characterized by regional sympathetic hyperactivity which has not been associated with Lyme disease. We report a 16-year-old female with clinical, radiological and scintigraphic features consistent with reflex sympathetic dystrophy. The usual causes of this syndrome were ruled out and antibodies against Borrelia burgdorferi were detected by immunofluorescence, enzyme immunoassay and Western blotting. Specific IgG and IgM levels had a progressive increase during three months. In Lyme borreliosis causes of false positives were excluded. Antigen antibody bands were detected in increasing number during the evolution, using sonicates of B. burgdorferi and patient's sera with the Western blotting technique. Our data suggest that reflex sympathetic dystrophy is another type of nervous system involvement in the multifaceted Lyme borreliosis. PMID- 2095903 TI - [Skin manifestations of infection by Borrelia burgdorferi]. AB - Interest in Lyme's disease is recent in Spain. We review the dermatological features of the disease caused by B. burgdorferi, its differential diagnosis and its therapy, with reference to three patients with Borrelia burgdorferi infection in whom the diagnosis was made on the basis of the dermatological picture. One patient had migratory erythema developing from the umbilical area, where he had been bitten by a tick. Another patient had arthritis of the knee and meningoradiculitis, together with multiple skin lesions. The last patient had atypical migratory erythema and concomitant arthritis. PMID- 2095904 TI - [VDRL and FTA-ABS reactivity in cerebrospinal fluid: our experience]. AB - The reactivity of 194 samples of CSF against VDRL and FTA-ABS was studied in patients attending the Clinical Hospital in Salamanca over a five years period. This laboratory was asked to rule out an etiology of syphilis. Twelve samples of CSF proved to be reactive (6.2%) against VDRL and/or FTA-ABS. Seven of these corresponded to six adults diagnosed as suffering from neurosyphilis and one to an infant with early congenital syphilis without neurological alterations; these had in common the presence of active syphilis and a reactive FTA-ABS in serum. In the CSF of the six cases of neurosyphilis, VDRL was reactive in two patients (33.3%) and FTA-ABS in five (83.3%). One minimally reactive VDRL and four FTA-ABS were detected in the remaining five patients, with no known previous history of syphilis, that were suffering from different neurological alterations and that had a nonreactive FTA-ABS in serum. The results obtained in this study point to inappropriate use in CSF of VDRL and FTA-ABS to exclude neurosyphilis in our hospital since only 3.6% of the CSF studied corresponded to patients diagnosed as suffering from neurosyphilis and also to the need for improving the criteria for patient selection. PMID- 2095906 TI - [Experimental studies]. PMID- 2095905 TI - [Search for antibodies against human immunodeficiency virus type 2 (HIV-2) in a sample of parenteral drug addicts (IVDA)]. AB - We have retrospectively investigated the antibodies against type 2 human immunodeficiency virus (Ac HIV-2) in sera from parenteral drug abusers (PDA) who had been previously investigated for HIV-1 and who fulfilled established criteria (trips, sexual contacts, etc.). Enzyme immunoassay (EIA) was positive in 7 individuals who were also carriers of HIV-1. When HIV-2 was confirmed with Western blot, in only one case a tenuous band against glycoprotein 105 (gp 105) and the remaining ones from the core was found. PMID- 2095907 TI - [Imported fever in a 4-year-old boy]. PMID- 2095908 TI - [HTLV-I and malignant hemopathies in Barcelona]. PMID- 2095909 TI - [Comparison of a competitive enzyme immunoassay with Western blot in the detection of anti-HIV-1]. PMID- 2095910 TI - [Absence of HIV-2 and HTLV-I infection in prostitutes]. PMID- 2095911 TI - [Enterocolitis caused by Blastocystis hominis and HIV infection]. PMID- 2095913 TI - [Increase in the frequency of cases of listeriosis in adults]. PMID- 2095912 TI - [Pleuropulmonary tuberculosis caused by Mycobacterium africanum in a white male]. PMID- 2095914 TI - [Syphilis and HIV infection]. PMID- 2095916 TI - Tumor suppressor genes. PMID- 2095915 TI - Tumor suppressor genes: studies with hybrid mouse cells. PMID- 2095917 TI - Defining the mechanisms of transformation through analysis of revertant cells. PMID- 2095918 TI - Role of differentiation induction in tumor suppression. PMID- 2095919 TI - Suppression of carcinogenesis: a role for TGF-beta and related molecules in prevention of cancer. PMID- 2095920 TI - Characterization and comparison of virulent bacteriophages of Streptococcus thermophilus isolated from yogurt. AB - Seven virulent bacteriophages of Streptococcus thermophilus were characterized at the molecular level and classified into 2 subgroups (A and B) by DNA/DNA hybridization experiments and analysis of their structural proteins. Two representatives of subgroups A and B were compared to 3 representatives of Neve's subgroups I, II and III (Neve et al, 1989) by Southern blot experiments. These isometric-headed phages possess a double-stranded DNA genome varying between 30 44 kilobase (kb) pairs. Subgroup A is composed of 3 phages (phi 57 as representative) with similar structural proteins as determined by sodium dodecyl sulfate-poly-acrylamide gel (SDS-PAGE) electrophoresis (estimated molecular weights of 31,000 and 27,500 for phage phi 57 and 32,000 and 27,000 for the 2 others). A common structural protein of 43,000 was found for phages of subgroup B. Phages phi 57 (subgroup A) and a10/J9 or PO (Neve's subgroups I or II, respectively) belonged to the same subgroup as determined by DNA/DNA hybridization experiments. Partial DNA homology was detected among all the phages tested except for phage phi ST27 of AW Jarvis. Phage-host interactions were also investigated by cross-propagation of the 7 studied phages on different indicator strains. A complete lack of correlation existed between the DNA homology grouping of the phages and their host range. Various restriction-modification systems were detected in some of the Streptococcus thermophilus strains. PMID- 2095921 TI - Acyl-CoA: 1-acyl-glycero-3-phosphoethanolamine O-acyltransferase and liver plasma membrane fluidity. AB - Investigations have been carried out on the influence of membrane lipid composition and physical state on acyl-CoA: 1-acyl-glycerol-3-phosphoethanolamine O-acyltransferase activity in rat liver plasma membranes. The lipid composition of the membranes was modified either by way of lipid transfer proteins or by partial delipidation with exogenous phospholipases and subsequent enrichment of the membranes with different phospholipids. The results indicated that membrane rigidification by enrichment of the membranes with DPPC or SM reduced the transfer of oleic and palmitic acid to lysophosphatidylethanolamine, whereas all phospholipids inducing membrane fluidization lead to acyltransferase activation. The eventual role of membrane fluidity in the deacylation-reacylation cycle is discussed. PMID- 2095922 TI - A radioactive assay for the physiological activity of the tryptophan synthetase alpha subunit in crude extracts of Escherichia coli. AB - A modified assay has been devised for the physiological reaction, indole-3 glycerol phosphate to Trp, of the enzyme tryptophan synthetase. The assay may be applied to crude bacterial extracts, and is based on the measurement of incorporation of radioactivity from [3H]Ser into Trp. Comparison with previous colorimetric assays indicates an improvement in sensitivity of about 30-fold, and advantages in terms of sample economy and simplified manipulation. PMID- 2095923 TI - Improved method for measuring the catalytic activity of tryptophan synthase alpha subunit in cell extracts. AB - An improved method has been developed for measuring the catalytic activity of tryptophan synthase alpha-subunit in cell extracts using the indole-3-glycerol phosphate (InGP)----tryptophan reaction. The method involves the chemical and enzymatic synthesis of the substrate InGP immediately before use and avoids the preparation of salt-free hydroxylamine. The method is more convenient, safer and more reliable than the traditional method employing the InGP----indole reaction. PMID- 2095924 TI - MoMuLV-derived self-inactivating retroviral vectors possessing multiple cloning sites and expressing the resistance to either G418 or hygromycin B. AB - To facilitate cloning procedures in recombinant murine leukemia virus-derived retroviruses, we have constructed vectors that both carry a polylinker with multiple restriction sites and express resistance to either G418 or hygromycin B. Our vectors are self-inactivating retroviruses that suppress interferences between LTR enhancers and internal promoters and avoid transcriptional stimulation of host cell genes. They can also be used as expression vectors in direct transfection assays, since no translation initiation codon lies between the 5' LTR and the cloning polylinker. PMID- 2095925 TI - Regulation of a thermostable alpha-amylase of Streptomyces thermoviolaceus CUB74: maltotriose is the smallest inducer. AB - We have examined induction and repression by various sugars and carbon sources of the synthesis of a thermostable alpha-amylase in its natural host, S thermoviolaceus CUB74. The smallest molecule capable of inducing synthesis of the enzyme was maltotriose whereas maltose had no effect which might suggest a different control system from that found in other streptomycete amylases. Addition of mannitol to the growth medium impeded the alpha-amylase induction whereas glucose had no effect. After cloning of its gene into a new streptomycete host, S lividans TK24, the S thermoviolaceus alpha-amylase could not be induced by any of the sugars tested. PMID- 2095926 TI - Serum cholesterol reduction with tamoxifen. AB - The serum cholesterol levels of 123 consecutively and newly diagnosed women with Stage I and II breast cancer taking tamoxifen were compared with a control group of 81 consecutively newly diagnosed women with Stage I and II breast cancer who were not taking a hormonal treatment or supplement. Other factors that were evaluated were age, menopausal status, tumor size, weight, height, Quetelet index, and smoking and alcohol intake history. The mean cholesterol change in patients on tamoxifen (34.2 +/- 3.6 mg/dl) was significantly greater than controls (1.0 +/- 4.1 mg/dl) (P less than 0.001). Serum cholesterol fell by more than 10 mg/dl in 72.9% of women on tamoxifen vs. 35.1% of controls and by more than 40 mg/dl in 39.9% of women on tamoxifen vs. 12.6% of controls. Multivariate analysis revealed that tamoxifen administration (P less than 0.0001), initial cholesterol level (P = 0.001), and age (P = 0.04) were significant factors in producing a decrease in serum cholesterol. The administration of tamoxifen as adjuvant therapy to women with newly diagnosed breast cancer resulted in a significant fall in serum cholesterol. This effect of tamoxifen on the serum cholesterol may prove to be an additional benefit in the form of reduced cardiovascular risk in these women. PMID- 2095927 TI - Megestrol acetate: phase II study of a single daily administration in advanced breast cancer. AB - A new formulation of megestrol acetate, a semisynthetic oral progestin used in the hormonal treatment of breast cancer, allows the administration of 160 mg of the drug in a single daily dose. Sixty-nine postmenopausal patients with advanced breast cancer have been treated with this regimen: five patients received megestrol acetate as first-line treatment of their metastatic disease, while all the others had been previously treated with one or more regimens of chemotherapy and/or hormone therapy. The median duration of the treatment for evaluable patients was 3 months (range 1-13+). Among 65 evaluable patients 2 complete responses and 12 partial responses (objective response rate 21.5%; 95% confidence limits 12.31%-33.49%) were observed. Median duration of response was 7 months (range 2-12+). Responses were observed both in visceral and in non-visceral sites of disease. Twenty-nine patients obtained a stabilization of disease (44.7%), and twenty-two progressed (33.8%). Median duration of stabilization was 4 months (range 3-13+). Median survival for all patients from the start of megestrol acetate was 9 months (range 1-22+). The most common side effect of therapy was weight gain, occurring in 36% of patients. Megestrol acetate on a single-daily dose schedule can be considered as an interesting hormonal treatment for advanced breast cancer, especially in the clinical instance of patients who, after having obtained a remission or stabilization of disease with tamoxifen, need further palliative treatment. PMID- 2095928 TI - Breast epithelial antigen levels and breast tumor antigen content. AB - The relationship between the primary tumor expression of a breast epithelial antigen, called non-penetrating glycoprotein (NPGP) or breast epithelial mucin, and the same patient's serum level of this antigen at the time of relapse was studied in 23 cases. The expression of NPGP on breast tumors was measured by immunoperoxidase staining using monoclonal antibody Mc5, and quantitated by a histopathological index created for this purpose. Serum levels were measured by a competitive RIA using the same monoclonal antibody. An inverse correlation between these parameters was found, such that tumors having high NPGP levels in serum had a low index, while low NPGP serum levels had a high index. These results show that cellular events in breast tumors could participate in determining NPGP serum levels in breast cancer. PMID- 2095929 TI - Inter-laboratory comparison of DNA flow cytometric results from paraffin-embedded breast carcinomas. AB - Consecutive sections from 33 paraffin-embedded human breast carcinomas without intratumor heterogeneity were sent for flow cytometric (FCM) DNA analysis in two experienced laboratories. FCM instruments, run conditions, and tumor disaggregation procedures were different in the two laboratories. In four cases (12%) the laboratories reported a different DNA ploidy and DNA index (DI). These variations were due to analytical reasons, differences in the detection rates of near-diploid and tetraploid DIs, not due to interpretation of data or the criteria used for aneuploidy. There was a significant correlation between S-phase fractions (SPF) obtained in the two laboratories (r = 0.90, p less than 0.0001) if only cases with concordant DI were included. Discordant DI usually led to very different SPF values. PMID- 2095930 TI - Serum placental isoferritin and breast cancer prognosis. PMID- 2095931 TI - Nuclear polymorphism--a prognostic parameter to evaluate local recurrence of female breast cancer. AB - Between 1980 and 1986 676 patients underwent surgery for primary breast cancer. Of these, 35 patients developed locoregional recurrence. Retrospective analysis of the spontaneous postoperative development revealed 2 groups: group A had subsequent distant metastases, group B was tumor-free after surgical treatment of local recurrence. Analysis of the commonly employed characterization criteria of primary tumors (tumor size, lymph node involvement, estrogen receptors, histologic grading of primary tumors, and excised locoregional recurrence) showed no statistically significant difference between the two groups. However, a more detailed differentiation of the subcriteria for the histologic grading according to Bloom and Richardson revealed a prevalence of anaplastic nuclei in the primary tumors of group A (9/11). Even in this small patient population the parameter of nuclear polymorphism revealed a highly significant statistical difference between the two groups. PMID- 2095932 TI - Development of a judicial response to substance abuse. AB - The American juvenile justice system continues to be an arena in which a myriad of varying values and practices come under constant challenge and close scrutiny, not only from those outside the system, but particularly by those within the system, those on the firing-line--the judges, court administrators, prosecutors, defenders, police, social workers and probation officers who are responsible for the operation of the system. Every juvenile court and the personnel who work with it are faced with the difficult process of evaluating and adapting to multiple "standards" and the challenges of implementing effective change within the perimeters of varying systems and statutes. The National Council of Juvenile and Family Court Judges recognizes that the responsibility for further improvement, for effective and long-lasting change, in a juvenile justice system that operates in a vastly complex society will rest even more heavily in the future where it has been in the past--on the individual judge and practitioner. PMID- 2095933 TI - Drug control strategies of United States law enforcement. AB - The American approach to drug control is conditioned by several national characteristics, including fragmentation of the law enforcement system, a 12,000 mile international boundary and a legal system that restricts police authority to search, arrest, detain, eavesdrop and maintain intelligence files. Drug problems in the United States, though, are by all accounts greater than in any other country. Enforcement has traditionally emphasized street-level arrests, investigation of distribution networks, crop eradication and smuggling interdiction. These practices can be shown to produce arrests and seizures, but there is little evidence to show that they reduce drug supply or drug abuse. More contemporary and promising approaches include community policing, problem oriented policing, financially oriented investigations, increased international co-operation and a renewed emphasis on drug demand reduction. The most pressing needs in law enforcement are (a) improved intelligence-gathering and analysis and (b) research on the illicit drug industry and on the effectiveness of drug control strategies. PMID- 2095934 TI - Projections for the future development of international drug control policies. AB - With the adoption of the Declaration and the Comprehensive Multidisciplinary Outline of Future Activities in Drug Abuse Control by the International Conference on Drug Abuse and Illicit Trafficking (ICDAIT) in 1987 and the formulation in 1988 of the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, the United Nations has made significant contributions to international drug control policy, in line with its responsibilities under article 55 of the Charter. Governments are acting, separately and through regional and other collective organizations, to adapt these policies to their own particular needs and to make the legislative changes needed to enable ratification of the new Convention. Simultaneously, the Commission on Narcotic Drugs continues to carry out its policy-making function by identifying areas of concern on which consensus can be achieved as well as appropriate techniques for achieving effective international co-operation as foreseen in the Charter of the United Nations. The present article draws attention to recent developments pointing to possible areas of policy formulation. These include enhanced cooperation of law enforcement agencies with overlapping jurisdictions; judicial methodology and inter-system co-operation to follow on from seizures from the illicit traffic and detention of suspects to consideration of treatment methodology; and adaptation of demand reduction techniques to target groups beyond the reach of formal educational institutions. The trend towards horizontal integration of trafficking networks is examined in the context of indications linking illicit traffic in psychotropic substances to the production and trade of chemical weapons, such as poison gas, and to the cultivation of new markets in response to the saturation of certain North American markets for specific illicit drugs. PMID- 2095935 TI - Women, drug control and the law. AB - Legal regulation of drugs in the United Kingdom of Great Britain and Northern Ireland has tended to centre on the criminalization of the production, supply, possession, purchase, use and abuse of drugs, in which women and men are generally treated similarly. Women have, however, received differential legal treatment in the context of their role as mothers, where drug use can result in what may be considered the ultimate sanction against drug use for a woman: the loss of custody of a child vis-a-vis another parent or guardian, an adopter or even the State. Even drug use prior to the birth of the child can be relevant. PMID- 2095936 TI - Preventive education to cope with the drug problems of Latin America. AB - Insufficient resources, services, staff, facilities and attention at the policymaking level are devoted to demand reduction measures, especially preventive education for young persons. Instead, emphasis is placed on and disproportionate resources are allocated to supply reduction measures and activities such as suppressing and/or limiting the availability of illicit drugs. Prevention policy constitutes a viable approach to solving the problem of illicit drug trafficking and consumption. The crux of the problem is not the availability of illicit drugs, but the demand of consumers for the substances. Preventive education for the young is an indispensable ingredient of effective prevention policy. The school environment can be instrumental in developing systematic and lasting preventive education. An essential condition, which, according to the author, is lacking in Latin America, is that educators should be provided with the training and training tools needed to enable them to perform properly as agents of prevention policy. A number of recommendations to reduce illicit drug demand and consumption through prevention are made, including giving priority to a comprehensive and systematically applied prevention policy focusing on the young and involving an educational approach and tools that are progressive and highly specialized, as well as research that is intensified and of better quality. PMID- 2095938 TI - Maritime drug trafficking: an underrated problem. AB - Seizure data indicate that a substantial proportion of the total quantity of drugs seized is confiscated from maritime modes of conveyance or has been transported by sea. The trafficking of narcotic drugs by sea has virtually become an industry comprised of many individual enterprises of varying size and organization. The maritime medium is one of the main ways by which drugs may enter some countries. In response to the problem, various sophisticated anti trafficking offensives and strategies have been established or contemplated in certain geographical areas. The shipment of drugs to the primary consuming countries has not been curbed, however, and there is every indication that the overall movement of drugs is still unimpeded. PMID- 2095937 TI - The experimental use of cocaine in human subjects. AB - Continuation of the practice of experimental administration of cocaine to cocaine addicted volunteers has been recommended by some investigators. The author's view is that the risk of experimental use of cocaine outweighs its benefits and that this practice should not be pursued. The author describes the damaging effects of cocaine on the cardiovascular system, particularly its ability to induce myocardial band necrosis, and the unique reinforcing properties of the drug. The legal and ethical issues raised by the experimental use of cocaine are also discussed. PMID- 2095939 TI - The legal regulation of narcotic drugs and psychotropic substances in the Union of Soviet Socialist Republics. PMID- 2095941 TI - The social psychiatry of later life. PMID- 2095940 TI - Sight and insight: regional cerebral metabolic activity in schizophrenia visualised by positron emission tomography, and competing neurodevelopmental perspectives. PMID- 2095942 TI - Relatives and patients as partners in the management of schizophrenia. The development of a service model. AB - Considerable advances have been made in the family management of schizophrenia but there remains a major challenge for the psychiatric services to integrate these innovations into clinical practice. A number of important issues need to be considered in developing routine clinical services: the problem of engaging families in a therapeutic programme; the utility of the concept of 'expressed emotion'; and procedures for clinical practice. The latter include the needs of low-EE families; maintaining quality of intervention in a clinical context; responding to the multiplicity of needs of the patient and family; and integrating family interventions with ongoing rehabilitation practice. A model of service provision is described. PMID- 2095944 TI - Responses of growth hormone to desipramine in endogenous and non-endogenous depression. AB - Desipramine, a monoamine reuptake inhibitor, was used to stimulate release of growth hormone (GH) in 29 DSM-III major depressives and in 10 healthy controls. Eighteen of the depressives showed a blunted response. The GH-stimulation test was unable to distinguish endogenous from non-endogenous patients. The 13 dexamethasone non-suppressors were more likely to have a blunted GH response than the 14 suppressors. The results indicate that at least a subset of non-endogenous depressives have significant neuroendocrine abnormality. PMID- 2095943 TI - Depression among elderly residents of local-authority residential homes. Its nature and the efficacy of intervention. AB - Of 390 residents in 12 local-authority homes for the elderly, 93 had evidence of depression on screening and underwent standard clinical assessment. Half had an affective disorder, and a further third had depressive symptoms in the setting of an organic mental disorder. The 93 residents had a high rate of physical illness and disability, undertook little social activity, and were visited infrequently. A range of interventions for depressed residents, the majority social in type, mostly proved difficult to implement. There was no evidence of efficacy of psychiatric intervention at three months; at one-year follow-up a quarter of study participants had died, and 28% of those who were reassessed for depression showed evidence of recovery. PMID- 2095946 TI - The friendships and recent life events of anxious and depressed school-age children. AB - The number of moderate to severe undesirable life events and the quality of friendships were compared between a consecutive series of 100 children aged 7-16 years with emotional disorders and a series of community controls matched for age, sex, and social class. Undesirable events and friendship difficulties exerted independent direct effects of similar magnitude on the probability of developing emotional disorders; 33% of disturbed children experienced both adversities compared with 6% of controls. An additive interaction was found for the two factors. The results were uninfluenced by the sex or pubertal status of the subjects. There appears to be no greater probability of being anxious rather than depressed in the presence of life events, alone or in combinations with friendship difficulties. Recent undesirable life events and friendship difficulties arise through independent social pathways and may exert their effects through different psychological mechanisms. PMID- 2095945 TI - The stress profile. AB - The Stress Profile consists of a number of questionnaires which have been developed to assess the severity of stress in nine areas of life: social habits, social relationships, life events, sexual problems, sleep, psychiatric symptoms, old age, menstrual stresses, and 'stress and the heart'. The questionnaires have been validated for inter-rater reliability and against the Hamilton anxiety and depression rating scales. Using the Profile, the inter-relationships between different stress areas can be assessed, appropriate treatments advised, and the response to treatment in relation to different components evaluated. PMID- 2095947 TI - Childhood sexual experiences with adults reported by women with eating disorders: an extended series. AB - A total of 158 women presenting with clinical eating disorders have been investigated using a self-report questionnaire and subsequent interview concerning their recollections of sexual experiences with adults before the age of 16 and later adverse sexual experiences. About a third reported events in childhood and over half described some adverse experiences. It may be that these experiences are relevant to the subsequent illness in some cases, but greater certainty must await further research. In the meantime, inquiring about such matters would seem to be advisable in the assessment and therapy of eating disordered patients. PMID- 2095949 TI - Violent death and mental illness. A study of a single catchment area over eight years. AB - The names of 412 residents of the catchment population of a district general hospital unit who died potentially self-inflicted deaths in the eight years 1974 81 were identified. They were classified as suicide (245), accidental death (126), and undetermined (41). In each group, over half had a lifetime history of psychiatric treatment and over a third were psychiatric patients at the time of their death. The relative risk of a violent death for those who died within a year of their last psychiatric contact was 27 times greater than that of residents with no recent psychiatric contact. The relative risk was highest for those aged 35-44 and lowest for those of 75 years and over. PMID- 2095948 TI - The influence of social factors on common mental disorders. Destabilisation and restitution. AB - This study distinguishes between processes that cause individuals to experience symptoms--destabilisation--and those that are associated with loss of symptoms over time--restitution. It is shown that different clinical, social, and personality variables are associated with each of these processes. Where destabilisation is concerned, it is shown that different variables were associated with the development of symptoms of anxiety and those of depression. Different variables were associated with restitution, and they did not show the same relationship with the symptom dimensions of anxiety and depression as those which were associated with destabilisation. PMID- 2095950 TI - Asperger's syndrome: to be or not to be? AB - It has been questioned whether Asperger's syndrome (AS) is in fact a specific (high functioning) subgroup of autism, rather than a distinct entity. Thirteen AS patients were compared with 13 autistic patients and 13 developmentally disordered controls. While there was symptom overlap between AS and autism, patients could be separated into one or other group. However, current criteria are based on symptoms, and it is argued that studies of genetics and treatment response are needed to elucidate the relationship between these developmental disorders. PMID- 2095951 TI - Mentally retarded criminal offenders in Denmark. AB - Based on data from the Danish Central Criminal Register, the total number of mentally retarded offenders serving statutory care orders on a census day decreased from 290 in 1973 to 91 in 1984. The reduction was caused by shorter sentences and a dramatic decrease in the number of sentenced borderline retarded offenders: the total number of sentences per year slightly decreased, and the number of first-time sentences was stable. Crimes of property are decreasing among this population, while violence, arson, and sexual offences are increasing. Behaviour disorder was found in 87.5% of 91 offenders serving care orders in 1984. Offensive behaviour was significantly predicted by early institutionalisation, having retarded or divorced parents of low socio-economic status, and behaviour disorder of social-aggressive type. Independent significant effects were attributed to behaviour disorder and low socioeconomic background. All predictors were closely correlated. Biological factors did not have any significant predictive value. PMID- 2095952 TI - A study of psychotropic medication given 'as required' in a regional secure unit. AB - Within the setting of a regional secure unit, all doses of medication given p.r.n. over three months were ascertained and the details of each administration determined from prescription charts and a semistructured interview with the nursing staff involved. Thirty-two patients were resident for all or part of the study, all compulsorily detained. Only 15 were given medication p.r.n.; compared with the other patients they were significantly younger and more likely to be detained under civil orders than under the criminal provisions of the Mental Health Act 1983. Rarely was the medication the sole intervention in a crisis. In terms of effects on the overall treatment programme of the patient, medication given p.r.n. seemed to have an impact in only one small subgroup. PMID- 2095953 TI - Changing interactions between bipolar affective disorder and anoxic brain damage. AB - A manic-depressive young woman received mild brain damage from anoxia after attempting suicide by hanging. The case conference was held to elucidate whether her subsequent symptoms were functional or organic, and what courses of treatment should be tried in this very refractory case. PMID- 2095954 TI - Asian patients and the HAD scale. PMID- 2095955 TI - HAD and ROC. PMID- 2095956 TI - CT findings in schizophrenia. PMID- 2095957 TI - Chronic psychoses in Turner's syndrome. PMID- 2095958 TI - Auditory hallucinations during oculogyric crises. PMID- 2095959 TI - Reviewing reviewers. PMID- 2095960 TI - Failure to convulse with ECT. PMID- 2095961 TI - Asian suicides. PMID- 2095962 TI - Olfaction and psychiatry. PMID- 2095964 TI - Gastroesophageal reflux. PMID- 2095965 TI - Gastroesophageal reflux and allergy. PMID- 2095963 TI - Durkheim's views on suicide. PMID- 2095966 TI - Interactions, associations, and relationships between the lungs and the esophagus. PMID- 2095967 TI - Interference between gastroesophageal reflux and sleep in near miss SIDS. AB - GER may be considered as one of the triggering factors in some apparently life threatening events or even SIDS. Also at the present time, many teams perform 24 h pH monitoring in at-risk infants and treat those with abnormal scores. However, further investigations are needed to answer the question: Which unknown additional factor(s) is present when a specific episode of GER causes apnea and/or bradycardia either during sleep or wakefulness? PMID- 2095969 TI - The relationship between gastroesophageal reflux and chronic respiratory diseases. PMID- 2095968 TI - Gastroesophageal reflux and upper airway diseases. AB - GER can have important impacts on the upper airway passages, and in turn, upper airway obstruction can certainly aggravate reflux. This relationship should be considered in the newborn or young infant, faced with a sudden life-threatening event, and in the older child or adult presenting with chronic head and neck complaints, either unexplained or unresponsive to adequate medical therapy. A causal relationship may be difficult to establish, based first on clinical expertise as a guideline, on laboratory tests, among which pharyngeal pH monitoring could be promising, and on response to medical antireflux therapy. A better understanding of the significance of high levels of reflux and defective acid clearance, as well as a more precise knowledge of the maturation and functioning of upper airway protective mechanisms, would open the way to more accurate diagnostic procedures, to a more reliable definition of the abnormal, and to greater efficiency in the management of these patients. PMID- 2095970 TI - Diagnosis of gastroesophageal reflux. PMID- 2095971 TI - Gastroesophageal reflux and chronic respiratory disease in adults. Influence and results of surgical therapy. PMID- 2095972 TI - [Primary pulmonary hypertension: a retrospective study of 13 patients]. AB - Twenty-four patients (9M and 15F, mean age 28 years) with primary pulmonary hypertension underwent cardiac catheterization in our institution from 1955 to 1989. The prevalence of the disease in our population was lower (0.2%) than that reported by other Authors (1%). Thirteen of these patients (4 M and 9 F, mean age 32 years) evaluated between January 1979 and December 1989, were followed. Five were alive after 52 +/- 30 months (Group A) while 8 died after 11 +/- 9 months (Group B). In Group B mean pulmonary pressure was significantly higher than in Group A (66.7 +/- 17.2 vs 41.2 +/- 19.0 mmHg, p less than 0.05, respectively). Cardiac index and systolic volume index were lower in Group B than in Group A (2.07 +/- 0.85 vs 3.72 +/- 1.32 l/min/m2, p less than 0.01 and 24.43 +/- 10.25 vs 41.08 +/- 16.97 ml/m2, p less than 0.05, respectively). Pulmonary resistance index and systemic resistance index were higher in Group B than in Group A (3039 +/- 1519 vs 1181 +/- 1236 dyne x s x cm-5/m2, p less than 0.01; 4277 +/- 1794 vs 2309 +/- 1238 dyne x s x cm-5/m2, p less than 0.01). One patient underwent repeated cardiac catheterization after 2 years. This patient showed a deterioration of the hemodynamic parameters, consistent with the worsening of the clinical conditions. In conclusion, in our population of patients with primary pulmonary hypertension, an increase in pulmonary artery pressure and pulmonary resistances, as well as a decrease in cardiac index, are associated with a reduced life expectancy. On the other hand, right atrial pressure does not affect mortality. PMID- 2095973 TI - Evaluation of the effects of gallopamil in patients with effort angina by transesophageal atrial pacing two-dimensional echocardiography. AB - Transesophageal atrial pacing (TAP) 2D echocardiography was performed after placebo (P) and gallopamil (G) (0.03 mg/kg iv) in 12 patients with stable, reproducible, effort angina. If compared to P study, during G the following changes were observed: 3 out of the 12 patients did not experience angina, time to ST-1mm increased from 5.3 +/- 1.3 to 6.6 +/- 1.6 min (p less than 0.05), wall motion score was improved both at 130 b/min (15.3 +/- 4.1 drug P, 17 +/- 4.8 drug G, p less than 0.01) and at 150 b/min (10.9 +/- 5.7 drug P, 12.8 +/- 6.3 drug G, p = 0.07). In conclusion, gallopamil has a beneficial effect on atrial pacing induced ischemia: it increases pacing time to ischemic threshold and reduces during ischemia the extent of dysfunctional myocardium. PMID- 2095974 TI - [Effects of magnesium pidolate on cardiovascular hemodynamics]. AB - Aim of this study is to define the hemodynamic effects of magnesium (Mg) in patients with ischemic heart disease. Thus, the effects of 1 g of Mg pidolate injected over 3 min iv were evaluated in 10 patients by analysis of pressure data from a micromanometer catheter in the left ventricle and of volume data derived from Doppler and 2-dimensional echocardiography. Recordings were made before and immediately after the injection, at 3, 5, and 8 min. At 5 min, Mg induced a significant reduction in left ventricular peak systolic pressure (from 132.4 +/- 19.4 to 122.7 +/- 17.5 mmHg, p = 0.015, with early filling notably augmented (E wave of Doppler curve; from 39.4 +/- 8.5 to 43.9 +/- 9.7 cm/s, p = 0.013) and a slight increase in cardiac output (from 6.23 +/- 1.4 to 6.9 +/- 1.7 l/min, p = 0.092). Heart rate increased (from 75.9 +/- 9.6 to 78.13 +/- 8.4 b/min, p = 0.062) and the constant of isovolumetric pressure decay decreased (from 48.9 +/- 13.2 to 45.7 +/- 14.9 ms, p = 0.065), probably as a final effect of aortic pressure reduction. The diastolic pressure-volume relationship was insignificantly displaced downward (p = 0.11) and to the right (p = 0.62). In conclusion, Mg unloads the ischemic left ventricle through a reduction of systemic aortic pressure, with a secondary increase in early filling; this increase may derive from a rise in the atrioventricular diastolic gradient, subsequent to an improvement in ventricular emptying. Active relaxation is improved, and passive diastolic properties are not affected, in spite of the reported calcium-antagonist action of the drug. PMID- 2095975 TI - [Coronary angioplasty with balloon catheter: construction materials and mechanical performance]. PMID- 2095976 TI - The significance of left ventricular morphology and function in dilated cardiomyopathy. PMID- 2095977 TI - Dilated and arrhythmogenous cardiomyopathies: old and new concepts. PMID- 2095978 TI - [Involvement of the immune system in atherosclerosis]. PMID- 2095979 TI - [Expansion of the infarct area in anterior myocardial infarct: a short-term clinical and echocardiographic study]. AB - Forty-five patients with a first anterior myocardial infarction were studied by serial two-dimensional echocardiographic examinations to evaluate the incidence, short-term evolution and clinical significance of infarct expansion. Infarct expansion was found in 26 patients (58%); in 22 cases it was detected at the first examination 24 hours after the onset of symptoms, while in the other 4 it developed later. In 20 (77%) patients expansion involved only the septal and apical regions, while in 6 (23%) it extended to the antero-lateral wall. Two out of 22 patients with early expansion died of cardiogenic shock; expansion of the infarcted area progressively increased in 10 of the remaining 20 patients and remained stable in the other 10. Compared to the patients without expansion those with expansion had a higher CK peak level, a greater number of pathological Q waves and a greater echocardiographic asynergy score; moreover, in-hospital mortality and the incidence of left ventricular failure were higher in the group with expansion (8% vs 0% and 54% vs 10% respectively). Thus our results show that in patients with anterior infarction, expansion is a frequent event which usually develops early and may have a progressive course; infarct expansion, especially when it is large and progressive, is associated with a high incidence of early left ventricular failure and has a poor prognostic significance. PMID- 2095980 TI - [Evaluation of the predictive stable hypertension validity during the ergometric test in borderline hypertension]. AB - Aim of this study was to assess blood pressure (BP) response to exercise in borderline hypertensive subjects and to evaluate its predictive value for subsequent established hypertension development: 74 male subjects (28 borderline subjects, 26 normotensive subjects and 20 subjects with established hypertension) underwent a maximal exercise testing in the sitting position with a bicycle ergometer at the beginning of the study and then after 1 and 2 years; besides casual BP was controlled every 3 months for 2 years. Systolic BP exceeding 220 and/or diastolic BP exceeding 105 mmHg at maximal exercise and/or diastolic BP exceeding 100 mmHg at th fifth min of recovery were considered as abnormal. On the basis of BP response to exercise we divided our study group in: normotensive subjects with a normal BP response (Group A: 88%); normotensive subjects with an abnormal BP response (Group B: 12%); borderline subjects with a normal BP response (Group C: 46%); borderline subjects with an abnormal BP response (Group D:56%). At the end of a 2-year follow-up established hypertension developed in 1 subject of Group B (33%), in 2 subjects of Group C (15%) and in 10 subjects of Group D (67%); 7 subjects of Group C returned to normotension (54%). The incidence of established hypertension is significantly higher in borderline subjects with an abnormal BP response to exercise. This finding is probably due to both functional and organic factors and stresses the predictive value of exercise testing in borderline hypertension. PMID- 2095982 TI - [Determination of naphthidrofuryl and naphthidrofurylic acid in human plasma using RP-HPLC and fluorimetric detection]. AB - An analytical method was developed for the determination of naphthidrofuryl and its principle metabolite--naphthidrofurylic acid in human plasma by the RP-HPLC method with fluorimetric detection. The analytical method is based on a single extraction with a 5 ml mixture ether: hexane (1:1 by volume), with salting out by means of potassium chloride after which the organic phase after centrifugation, evaporation and reconstitution is sprayed on the reverse phase of HPLC and the separated substances are determined fluorimetrically (excitation 271 nm, emission 240 nm). Lonazolac served as the internal standard. The mobile phase consisted of 72% methanol, 1% triethylamine, 0.6% phosphoric acid. Optimization of the composition of the mobile phase from the aspect of the amino base, dependence of the percent content of methanol in the mobile phase and dependence of the recovery of substances on the composition of the extracting reagent are presented. The limit of detection was 4 ng/ml of plasma for naphthidrofuryl. The stability of compounds (a minimum of 2 months) and interference of some other drugs are shown. PMID- 2095983 TI - [Requirements for standards for monoclonal anti-A and anti-B antibodies]. AB - On the model of the Soviet monoclonal anti-A and anti-B antibody--erythrocytes of the groups A1, A2, A1B and A2B the conditions for the elaboration of the branch standard for anti-A and anti-B monoclonal antibodies were worked out. In comparison with the standard for human sera determining the ABO groups, the requirement for avidity can be increased, furthermore it seems necessary to determine the percentage of non-A blood cells in the A2B group, which should not exceed 30%, and the percentage of non-B blood cells in A1B erythrocytes, which should not exceed 10%. PMID- 2095981 TI - Ca2+ entry in T cells is activated by emptying the inositol 1,4,5-triphosphate sensitive Ca2+ pool. AB - Using alpha-linolenic acid (ALA), one of several polyunsaturated fatty acids (PUFAs) that have previously been shown to both mobilize intracellular Ca2+ from the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ pool independently of IP3 production and inhibit Ca2+ influx, the relationship between Ca2+ mobilization from intracellular stores and Ca2+ influx in T cells (JURKAT) was studied. JURKAT cells were treated with 30 microM ALA to deplete the IP3-sensitive Ca2+ pool. When the intracellular free Ca2+ concentration [( Ca2+]i) returned to basal level, fatty acid free bovine serum albumin (BSA) was added to remove extracellular and membrane bound ALA. This resulted in a sustained increase in [Ca2+]i in the absence of inositol phosphates' formation. This sustained increase in [Ca2+]i was insensitive to protein kinase C activation but was inhibited by Ni2+ ions. The extent of Ca2+ influx was found to be correlated to the amount of Ca2+ initially discharged from the IP3-sensitive Ca2+ pool by sub-optimal concentrations of ALA. Ligation of the CD3 complex of the T cell antigen receptor with an anti-CD3 antibody (OKT3) during the sustained [Ca2+]i increased (induced by a sub-optimal concentration of ALA), produced a greater response. No increase in the sustained response was observed when the CD3 complex was activated in cells pretreated with an optimal concentration of ALA. In summary, Ca2+ entry in T cells is activated by emptying of the IP3-sensitive Ca2+ pool which can be dissociated from inositol phosphate production. The rate of Ca2+ influx appears to be closely correlated to the initial discharge of Ca2+ from the IP3-sensitive Ca2+ pool, suggesting that Ca2+ may first enter the depleted pool and then is released into the cytosol. PMID- 2095984 TI - [Unscheduled DNA synthesis and evaluation of the effects of drugs]. AB - Unplanned DNA synthesis (UDS) represents one of the methods for the evaluation of genetic risk due to the action of xenobiotics in the organism. UDS is a parameter enabling quantification of the process of excisional repair of DNA, which results in the regeneration of the integrity of the genetic information (i. e,. correct sequence of nucleotides in DNA) after interaction with a mutagen. If the activity of the repair enzymic systems is not sufficient, the gene expression is affected, disorders in the functions of the damaged cells and tissues occur, or the cells die. The most important result is, however, the initiation of the process of carcinogenesis. A study of UDS within the framework of testing of novel drugs would markedly contribute to reveal possible negative as well as positive effects of the drugs tested both in vitro and in vivo tests. The present paper thus discusses possible uses of UDS study within preclinical and clinical testing of novel drugs. PMID- 2095986 TI - [Present problems and perspectives in pharmacy education and use of the pharmacist in practice]. PMID- 2095985 TI - [The importance of studying lipid peroxidation in testing new drugs]. AB - The drugs which are foreign to the organism can increase the production of free oxygen radicals either spontaneously or by means of metabolic activation, or they can act as inhibitors of protective enzymic systems. They can thus activate the process of peroxidation of lipids (LPO) causing gradual structural degradation of biomembranes, thus negatively affecting the course of both pathological and physiological processes in the organism. Investigation of the inductive or inhibitory effect of newly developed drugs on LPO should become a part of their preclinical and clinical testing. The present paper proposes and recommends on the basis of the present authors' results the methodical approaches to the investigation of LPO processes. PMID- 2095987 TI - [Basic pharmaceutical categories]. PMID- 2095989 TI - Hydrocarbon chain packing modes in lipids: effect of altered sub-cell dimensions and chain rotation. AB - The lateral hydrocarbon chain packing modes of lipids have been described in terms of specific hydrocarbon sub-cells as deduced from single crystal structural studies. To understand the changes in hydrocarbon chain packing in lipid bilayers induced by variations in temperature, hydration, ion-binding, etc., we have examined the effect on the calculated X-ray diffraction pattern of (a) systematic variations in the dimensions of the hydrocarbon sub-cell and (b) the effect of chain rotation at fixed lattice sites. For the O perpendicular (orthorhombic) sub cell, the a and b sub-cell parameters were varied from as = 4.96 to 4.85 A and bs = 7.42 to 8.40 A in six steps and the positions (s = 2 sin theta/lambda) and intensities (Icalc = F2) of the strong sub-cell reflections calculated. In this way, the conversion of the O perpendicular sub-cell (with either fixed chain orientations or simulated chain rotation) to the hexagonal (H) sub-cell (with chain rotation) was followed. Notably, the two strong reflections characteristic of the O perpendicular sub-cell at 4.12 A (110) and 3.71 A (020) show progressive shifts in position and intensity, finally merging to give the strong (O1O) reflection at 4.2 A characteristic of the hexagonal sub-cell. Similar calculations were performed for the orthorhombic (O' perpendicular) and monoclinic (M parallel) sub-cells. This approach can be used to analyze changes in the X-ray diffraction data due to modifications of the hydrocarbon chain packing modes characteristic of simple and complex lipids. PMID- 2095988 TI - Interaction of the herbicide atrazine with model membranes. II: Effect of atrazine on fusion of phospholipid vesicles. AB - The effect of atrazine on Ca2+ induced fusion of cardiolipin(CL) and phosphatidylserine (PS) vesicles is studied by Tb3+/dipicolinic acid fluorescence and turbidity measurements. The interaction of herbicide with CL and PS membranes is studied by DPH fluorescence polarization. At low concentrations the pesticide partially inhibits fusion, especially in CL vesicles. Higher concentrations of atrazine decrease inhibition of fusion in CL, while fusion is slightly increased in PS. The Ca2(+)-induced increase of turbidity is not affected by atrazine in both PS and CL aggregation experiments. DPH polarization measurements show a perturbation only of the membrane hydrophobic core of PS, in presence of Ca2+. It is hypothesized that this biphasic effect shown by low and high atrazine concentrations on Ca2(+)-induced fusion of vesicles is due to a different localization of the pesticide in the membrane. PMID- 2095990 TI - Infrared and time-resolved fluorescence spectroscopic studies of the polymorphic phase behavior of phosphatidylethanolamine/diacylglycerol lipid mixtures. AB - Fourier transform infrared (FTIR) and time-resolved fluorescence spectroscopy have been employed to examine the structural dynamics of lipid fatty acyl chains and lipid/water interfacial region of a binary lipid mixture containing unsaturated phosphatidylethanolamine (PE) and diacylglycerol (DG). Infrared vibrational frequencies of the CH2 symmetric stretching and the C = O stretching bands of the lipids were measured at different lipid compositions and temperatures. For 0% DG, the lamellar gel to lamellar liquid crystalline (L beta L alpha) and the L alpha to inverted hexagonal (L alpha-HII) phase transitions were observed at approximately 15 degrees and 55 degrees C, respectively. As the DG content increased gradually from 0% to 15%, the L alpha-HII phase transition temperature decreased drastically while the L beta-L alpha phase transition temperature decreased only slightly. At 10% DG, a merge of these two phase transitions was noticed at approximately 10 degrees C. For the composition study at 23 degrees C, the L alpha-HII transition occurred at approximately 6-10% DG as indicated by abrupt increases in both the CH2 and C = O stretching frequencies at those DG contents. Using time-resolved fluorescence spectroscopy, abrupt decreases in both the normalized long time residual and the initial slope of the anisotropy decay function of lipid probes, 1-palmitoyl-2-[[2-[4-(6-phenyl-trans 1,3,5- hexatrienyl)phenyl]ethyl]carbonyl]-3-sn-phosphatidylcholine, in these PE/DG mixtures were observed at the L alpha-HII phase transition. These changes in the anisotropy decay parameters suggested that the rotational dynamics and orientational packing of the lipids were altered at the composition-induced L alpha-HII transition, and agreed with a previous temperature-induced L alpha-HII transition study on pure unsaturated PE (Cheng (1989) Biophys. J. 55, 1025-1031). The fluorescence lifetime of water soluble probes, 8,1-anilinonapthalenes sulfonate acid, in PE/DG mixtures increased abruptly at the L alpha-HII phase transition, suggesting that the conformation and hydration of the lipid/water interfacial region also undergo significant changes at the L alpha-HII transition. PMID- 2095991 TI - Enhancement of biophysical activity of lung surfactant extracts and phospholipid apoprotein mixtures by surfactant protein A. AB - The effects of surfactant protein (SP)-A on the dynamic surface tension lowering and resistance to inhibition of dispersions of calf lung surfactant extract (CLSE) and mixtures of synthetic phospholipids combined with SP-B,C hydrophobic apoproteins were studied at 37 degrees C and rapid cycling rate (20 cycles/min). Addition of SP-A to CLSE, which already contains SP-B and -C, gave a slight improvement in the time course of surface tension lowering on an oscillating bubble apparatus in the absence of inhibitory protein molecules such as albumin or hemoglobin. However, when these proteins were present at concentrations of 10 50 mg/ml, SP-A substantially improved the resistance of CLSE to their inhibitory effects. The beneficial effect of SP-A required the presence of Ca2+ ions, and disappeared when EDTA was substituted for this divalent cation in the subphase. The effect was also retained when SP-A was heated to 50 degrees C prior to addition to CLSE, but was abolished by heating SP-A to 99 degrees C. Additional studies showed that similar improvements in resistance to inhibition were found when SP-A was added to synthetic mixtures of dipalmitoyl phosphatidylcholine (DPPC):egg phosphatidylglycerol (PG) (80:20 by weight) reconstituted with 1% SP-B or SP-B and -C, but not to phospholipid mixtures containing only SP-C. The requirements for SP-B and calcium for the beneficial effects of SP-A on surface activity suggest that the formation of ordered, larger phospholipid-apoprotein aggregates may be involved in the process. The finding that SP-A enhances the ability of CLSE and other surfactant mixtures containing SP-B to resist inhibition is an advantage that will need to be weighed against other factors such as increased antigenicity and heat sensitivity in therapeutic applications in surfactant replacement therapy. PMID- 2095992 TI - Interaction of cholesterol with saturated phospholipids: role of the C(17) side chain. AB - Cholesterol and 5-androsten-3 beta-ol differ structurally only in the presence of an eight carbon side chain at the C(17) position in the former sterol. Both molecules decrease the main transition enthalpy change (delta H) in a series of phosphatidylcholines and phosphatidylethanolamines, of acyl chain length n, with the reduction being a linear function of sterol concentration (c). The sterol concentrations at which delta H = 0 bear a straight line relationship to n and are equivalent for both cholesterol and 5-androsten-3 beta-ol. In addition, both sterols give identical delta H versus c slopes. These results underscore the importance of acyl chain length in the cholesterol/phospholipid interaction and also indicate that the cholesterol C(17) side group is not an essential requirement for the capacity of the sterol to decrease the enthalpy change of the main transition. PMID- 2095993 TI - [Construction of a genomic DNA library of Toxoplasma gondii (ZS2 strain), screening of specific clone and DNA diagnosis of toxoplasmosis]. AB - We have constructed a genomic DNA library of Toxoplasma gondii (ZS2 strain) and screened out a specific DNA sequence for T. gondii. The restriction map of the cloned DNA fragment (1.1kb) was analysed. The Southern and dot-blot analyses showed that the 32P-labeled cloned DNA fragment hybridized to the parasite DNA, DNAs from peripheral white blood cells and thymus of baby pigs artificially infected with T. gondii and DNAs of T. gondii- positive anencephalus and hydrocephalus, but did not hybridize to DNAs from controls, i. e., normal human and baby pig peripheral white blood cells, spleen of normal mouse, Plasmodium falciparum, Pneumocystis carinii and pBR322. As few as 100 T. gondii parasites or 500pg purified DNA from T. gondii can be detected by dot blot hybridization. This established DNA probe method was specific and sensitive and has been successfully used in detecting various cases infected with T. gondii. PMID- 2095994 TI - [Detection of circulating antigen and/or antigen-antibody complex by using McAb against surface membrane antigen of adult Schistosoma japonicum]. AB - In the present paper, the results of detecting circulating antigen and/or antigen antibody complexes by McAb against surface membrane antigen of adult Schistosoma japonicum were reported. The McAb, coded as 8SE4, was prepared by fusion of SP2/0 myeloma cells with spleen cells of the BALB/c mice immunized with the saline extract of adult S. japonicum. The 8SE4- directed antigen was proved to be located on the surface of the adult worm. After being purified by a DE52 column, 8SE4 was labelled with HRP and the conjugate (HRP-8SE4) was used in the test. For testing, the serum sample was first incubated with HRP-8SE4, then PEG (mw. 6,000) was added to precipitate the antigen-antibody complex. Upon centrifugation, OPD was added to the precipitate. Results were read by ELISA reader at 492nm. The OD value was found to be proportional to the amount of circulating antigen and/or antigen-antibody complexes. Results from 5 heavily infected (1,500-2,000 cercariae) rabbits showed that the OD values were raised significantly at the 6th week post infection, being 1.9-4.5 times higher than those before infection. The OD values of the 5 rabbits each lightly infected with 10-500 cercariae were also markedly raised 6 weeks post infection and reached the peak at the 8th week, then maintained in high levels until 11th week post infection. The worm burden of the 5 lightly infected rabbits were 4-326. No obvious correlations between OD values and worm loads were observed. The results suggested the existence of surface membrane-related antigen and/or antigen-antibody complexes in the circulation of infected rabbits. PMID- 2095995 TI - [Free amino acid components of cystic fluid of Cysticercus cellulosae]. AB - The free amino acids in the cystic fluid of Cysticercus cellulosae were determined quantitatively by using automatic amino acid analyzer. The cystic fluids of both subcutaneous-muscular Cysticercus cellulosae from 14 pigs and cerebral Cysticercus cellulosae from 10 pigs were detected. Among the 18 amino acids detected, alanine was found to be the predominant amino acid in both of the cystic fluids. The quantities of glycine and proline were higher than other amino acids in subcutaneous-muscular Cysticercus cellulosae, while threonine was higher than the rest in the cerebral Cysticercus cellulosae. A comparison was made between the quantities of amino acids in the fluids of both subcutaneous-muscular and cerebral Cysticercus cellulosae of 7 pigs by the T-test method. The results showed that the quantities of 12 out of 15 amino acids were significantly different, with particular reference to threonine, alanine, serine, and valine, suggesting that the difference in the metabolism of amino acids in Cysticercus may be related to the parasite's location in their respective hosts. PMID- 2095996 TI - [Studies on chromosomes of periodic Brugia malayi]. AB - A study was carried out on the chromosomes of periodic Brugia malayi using air drying preparations of testis, ovary and uterus. The results showed that the oogonial metaphase consisted of 4 pairs of small-sized autosomes and one pair of large-sized sex-chromosomes, that the spermatogonial metaphase consisted of 4 pairs of small-sized autosomes and one large-sized and one medium-sized sex chromosome, the oocytes at diakinesis had 5 bivalents, the secondary spermatocytes 5 univalents and the fertilized eggs 10 chromosomes. The above mentioned findings revealed that the chromosome number was 2n = 10 and that the sex-determining mechanism was of the XY-XX type in this type of B. malayi. PMID- 2095998 TI - [Quantitative study on infestation and distribution of human Demodex on the face]. AB - We have tried to use 1.2 cm x 5 cm (6 cm2) adhesive cellophane tape technique for quantitative detection of Demodex. 618 mites were detected on the 24 tapes applied on various parts of the face of a healthy individual. In an investigation of 8 person-times, the numbers of mites found on various parts of the face were in the following order: upper-cheek (233), mid-cheek (153), lower-cheek (114), chin (78), forehead (59.5), nose (55), infraorbital (54.5), paraoral (49.5), nasal groove (45), mites found on other parts being negligible. Demodex brevis were found scattering singly on the tapes, while D. follicutorum were found 1-6 in number in one or several follicles. All of them were in the follicle opening, indicating that transmission was readily affected through direct or indirect contacts. The results also showed that when a large number of mites were sticked off, the intensity of infestation was decreased. PMID- 2095997 TI - [On the transmission role of residual microfilaremia cases in the area with filariasis virtually eradicated]. AB - The transmission role of the residual microfilaremia cases was studied in Pingle Village, Liangqing Township, Yongning County where bancroftian filariasis had been virtually eradicated during 1984-1988. The results indicated that after the microfilarial rate of the human population met the criterion of elimination of filariasis, namely below 1% of the total population in all the administrative villages, and the average density of microfilaria being around 5 per 60 microliters peripheral blood, subsequent control measures might be no longer instituted while the microfilaria rate and its density could continue to decline. Some residual microfilaremiae cases having higher microfilarial density turned negative gradually, so did the natural infection rate of Culex quinquefasciatus with filaria larvae and its density year by year. No filaria larvae were found in vector mosquitoes in 1987-1988. The authors deemed that the filariasis transmission in this area has been interrupted. PMID- 2095999 TI - [Successful axenic cultivation of a local human strain of Giardia lamblia in suckling gerbil]. AB - G. lamblia cysts isolated from the fresh feces of a Giardia-infected boy in Beijing rural area were inoculated into suckling gerbils (Meriones unguiculatus). Trophozoites of G. lamblia obtained from the intestines of infected gerbils were cultivated in modified TYI-S-33 medium enriched with dehydrated bovine bile. The parasites grew luxuriantly and formed an intensive monolayer on the surface of the culture tube on day 14 after initial cultivation. The culture has been maintained for more than 12 months and more than 120 subcultures have been made. The growth curve of the organism showed that the peak growth of the trophozoites was attained at the 120th hour after seeding. The generation time was 15 +/- 2.0 hours. Periodic examinations of Giardia cultures for bacteria contamination, with Petri dishes of blood agar and beef broth, proved negative. After being cryopreserved in liquid nitrogen for 1 week or longer, the average viable rate of the organism was 65.7% and the resuscitated parasites grew luxuriantly in subcultures. PMID- 2096000 TI - [Studies on the efficacy of five repellents against Phlebotomus alexandri]. AB - The efficacy of five repellents were tested against Phlebotomus alexandri both in the laboratory and in the field in Meiyaogou, Turfan City, Xinjiang Uygur Autonomous Region during 1986-1987. A total of 3,301 female Ph. alexandri were used in the laboratory and 306 man-times of volunteers were tested in the field. At a dose of 0.25 microliters/cm2, the protective durations of mosquito repellent perfume (MRP), N, N-diethyl-mtaluamide (DETA), mosquito repellent liquid (MRL), dimethyl phthalate (DMP) and dibutyl phthalate (DBP) were 7.50 h, 5.00 h, 3.75 h, 1.25 h and 1.00 h, respectively. At a dose of 0.75 mg/cm2, the protective durations of the essential balms of DETA, DMP and DBP were 5.50 h, 3.50 h and 3.00 h, respectively. The repelling effect on volunteers in the field was the same as that tested in the laboratory. The relative efficacy of the five repellents was in the order of MRP greater than DETA greater than MRL greater than DMP greater than DBP. The above-mentioned repellents may be of practical use for individual protection against kala-azar transmission in the field. PMID- 2096001 TI - [Dot-ELISA in the diagnosis of neurocysticercosis]. AB - The dot-enzyme-linked immunosorbent assay was used to detect Cysticercus cellulosae antibodies in sera of patients with neurocysticercosis. Among 108 confirmed cases of neurocysticercosis 81.6-96.1% showed positive reactions. Two out of 54 normal control sera reacted at a serum dilution of 1:20, but none at a 1:40 (range 40-640). No cross reactions were observed with sera from cases of paragonimiasis and clonorchiasis, but it did occur to some extent with sera from cases of echinococcosis and cerebrovascular diseases. The results indicated that the dot-ELISA was sensitive, specific and economic for the diagnosis of neurocysticercosis. PMID- 2096002 TI - [Studies on dynamics of antibodies in sera from rabbits immunized with homologous and heterologous adult filarial antigens]. AB - The indirect immunofluorescent antibody test (IFAT) and immunoenzymatic staining technique (IEST) with frozen sections of Brugia malayi and Setaria cervi adult worms as antigens were used to detect IgG levels in rabbits immunized with three different filarial antigens. The results showed the dynamics of the specific IgG antibody in the course of immunization. The peaks (GMRT 76.11-861.08) of IgG levels in immunized rabbits appeared at the 4th week after primary immunization, which returned to (4.00-32.0 up to the 8th week after primary immunization and rose to (20.11-181.02) at the 1st week after second immunization. It is suggested that IFAT and IEST, especially the latter, can be applied for serodiagnosis of filarial infection and both antigens are considered to be of similar diagnostic effect. PMID- 2096003 TI - [Intestinal myiasis in Macao]. AB - Six cases of intestinal myiasis were diagnosed in Macao from January 1987 to August 1989, during a survey of intestinal parasites in inhabitants and on stool routine examination in hospitalized patients. The species of flies identified were Stomoxys calcitrans in 4 cases and Megalesia (Megalesia) insulana in 2 cases, M. insulana being a new record in mainland of China. During the survey of intestinal parasites 1889 human fecal samples were collected from Chinese inhabitants. 45 samples were collected on September 2 and 15 samples on September 11, 1987 in an aged home. Among them 4 samples were found to have some moving larvae, which were later identified morphologically as S. calcitrans. All these four cases were old ladies living in the aged home and they complained of mild diarrhea and abdominal pain. The fifth case was a patient with dermatosis, who had an eosinophil count of 18%. On stool examination, eggs of Clonorchis sinensis and larvae of flies were found. These larvae were cultured in food stuff containing wheat bran (100g), milk powder (18g) and water (200ml) at 30 degrees C. Within a week these larvae became pupa from which hatched adult flies identified as M. insulana which were known to be distributed in the Philippines and Hawaii but not found in the mainland of China before. 3 months later the stool from the patient was re-examined, about 200 larvae were counted in 5 ml of feces, the fly species being the same. The sixth patient was a pediatric case, again in his stool sample larvae of flies were found which were identified as M. insulana after culture. M. insulana is distributed in the Philippines, Hawaii, etc. Since a great amount of fruits was constantly imported from the Philippines and Hawaii, it remains to be confirmed whether M. insulana is imported into Macao through fruits. PMID- 2096004 TI - [Clinical manifestation and treatment of pulmonary acariasis]. AB - A survey on pulmonary acariasis was carried out in the grain store and in the Chinese medicinal herb plant. Of 363 persons examined, 92(25.3%) were mites positive in their sputum. 65 of them had symptoms and signs attributed to pulmonary acariasis, the incidence being 17.9%. The main clinical manifestations were productive cough, hemoptysis, chest pain, dyspnea asthma and marked eosinophilia. Roentgenogram of these cases revealed widening hilum shadow, increased and disordered lung markings, multiple cloudy shadow and nodular opacities ranging from 1-5mm in diameter scattered throughout the lower field of lungs. All the patients were treated with three courses of metronidazole. In each course a daily dose of 0.6g (0.2g tid) or 0.8g (0.4g bid) was given orally for seven days with an interval of 7-10 days between two courses. After three courses, the clinical manifestations and radiographic findings were much improved in most cases, eosinophilia dropped to normal limit, mites disappeared from sputum in 94.4% of patients. All these showed that metronidazole is rather effective in treating pulmonary acariasis. PMID- 2096005 TI - Autoantibodies to the TSH receptor in patients with autoimmune thyroid disease. PMID- 2096006 TI - The immunoreactive inhibin secretion pattern in the midluteal phase: relationships with luteinizing hormone and progesterone. AB - With the development of a sensitive radioimmunoassay for inhibin, luteal phase inhibin levels have been noted to parallel progesterone levels and be acutely dependent upon luteinizing hormone (LH) stimulation. To define the midluteal secretory pattern of immunoreactive inhibin and its relationships with LH and progesterone, blood samples were obtained from five normal women every 20 min for a period of 24 h. Individual data series of LH, progesterone and inhibin were analysed for pulsatile secretion using an adaptive-threshold method. Inhibin levels exhibited a relatively frequent, low-amplitude pulsatile secretory pattern (14.6 +/- 6.9 pulses/24 h (mean +/- SE), amplitude = 17% of the mean inhibin level). In contrast, LH levels demonstrated an infrequent high amplitude secretory pattern (6.2 +/- 0.7 pulses/24 h, amplitude = 139% of the mean LH level). The average progesterone pulse frequency and amplitude were intermediate to LH and inhibin (9.2 +/- 1.2 pulses/24 h, amplitude = 36% of the mean progesterone level). In addition, each individual's hormone data were analysed for coincident pulsatile secretion and cross-correlations were performed on the data, with one hormone pattern shifted relative to another by 20-min time intervals. None of the individual inhibin data series showed significant pulse coincidence when compared to the LH or progesterone data series. The cross correlation analysis, however, revealed a significant (P less than 0.05) relationship in general trends between the inhibin and LH data series, and the inhibin and progesterone data series in three subjects. PMID- 2096007 TI - Pulsatile GnRH-stimulated LH release from the human fetal pituitary in vitro: sex associated differences. AB - An in-vitro perfusion system was utilized to examine LH release from human fetal (19-24 weeks gestation) anterior pituitaries during repetitive GnRH stimulations. Pituitaries (five male, four female) were dissected into halves, and one hemipituitary of each pair was stimulated with 10-min pulses of 1 nM GnRH administered at 60-min intervals over 24h, whereas the matching hemipituitary received pulses of medium alone. Basal (no GnRH stimulation) LH release from female hemipituitaries was significantly (P less than 0.01) greater than from male hemipituitaries, and the amplitude of LH release associated with GnRH pulses was sixfold greater (P less than 0.001) with female hemipituitaries. Furthermore, the magnitude of LH release associated with individual GnRH pulses was significantly (P less than 0.001) enhanced during the course of female hemipituitary perfusions, but not during perifusion of male hemipituitaries. These studies demonstrate that LH secretion by the female, but not male, mid gestational human fetal pituitary is increased in response to a physiological pattern and interval of repeated pulsatile GnRH stimulation in vitro. PMID- 2096008 TI - The dawn phenomenon is related to overnight growth hormone release in adolescent diabetics. AB - We have investigated the relation between nocturnal insulin requirements and nocturnal growth hormone (GH) release in 26 diabetic adolescents at various puberty stages and have examined the effect of nocturnal GH suppression on pre breakfast insulin requirement. In all the studies, euglycaemia was maintained overnight using a computer-calculated variable-rate insulin infusion, and 15-min blood samples were collected for GH assay. During initial clamp studies, insulin infusion rates were greater from 0500-0800 h (15.22 +/- 0.95 mU/kg/h, mean +/- SEM) than from 0100-0400 h (12.42 +/- 0.84 mU/kg/h, P less than 0.001). The increase in insulin infusion rate correlated with mean overnight GH concentration (r = 0.68, P less than 0.001), and was maximal at puberty stage 3 in both sexes. In seven of the subjects, a second identical clamp was performed following administration of 100 mg oral pirenzepine. During these studies, mean overnight GH levels were reduced by 11-85%, from 17.6 +/- 1.6 to 7.5 +/- 2.2 mU/l; P less than 0.01. Insulin requirements were not significantly different between the periods 0100-0400 and 0500-0800 h during these studies, and the reduction in pre breakfast (0500-0800 h) insulin requirement when compared with the baseline studies correlated with the fall in GH secretion (rs = 0.82, P less than 0.01). The dawn increase in insulin requirement in adolescents with IDDM is related to the overnight GH secretion during puberty, and pre-breakfast insulin requirement can be reduced by suppressing nocturnal GH release. PMID- 2096009 TI - Glucose metabolism in quinine-treated patients with uncomplicated falciparum malaria. AB - To investigate host and drug effects on glucose metabolism in acute falciparum malaria, 10 previously untreated, fasting Thai males with uncomplicated infections were given a 2-h intravenous glucose infusion (5 mg/kg ideal body weight min) with an infusion of quinine dihydrochloride (10 mg/kg body weight) during the second hour. Eight patients were restudied in convalescence. Fasting plasma glucose (mean +/- SD) and insulin (geometric mean (-SD to + SD] were higher during acute illness (5.5 +/- 1.0 mmol/l and 6.2 (5.0-7.7) mU/l) than in convalescence (4.2 +/- 0.25 mmol/l and 3.7 (2.1-6.7) mU/l; P less than 0.001 and P = 0.058 respectively). After 1 h, both plasma glucose (9.3 +/- 1.4 vs 7.5 +/- 0.8 mmol/l, P less than 0.001) and insulin (21.2 (13.8-32.5) vs 15.2 (11.2-20.8) mU/l, P = 0.089) remained higher during acute illness; mathematical model (CIGMA) assessment of these values indicated lower tissue insulin sensitivity on admission (97% (71-134] than in convalescence (139% (109-178), P less than 0.025) but normal beta-cell function on both occasions. Two-hour plasma glucose (9.5 +/- 2.0 mmol/l) and insulin (81.8 (51.5-129.9) mU/l) concentrations during acute illness were also significantly higher than in convalescence (7.2 +/- 1.2 mmol/l and 40.1 (23.5-68.4) mU/l, P less than or equal to 0.025) despite similar end infusion free plasma quinine concentrations (P greater than 0.5). Basal plasma free fatty acid concentrations were increased in acute illness (0.68 +/- 0.24 vs 0.21 +/- 0.12 mmol/l, P less than 0.001) but fell to low levels at 2 h in both studies. These data suggest tissue insulin resistance and augmented quinine stimulated insulin secretion in acute falciparum malaria, factors which are likely to influence the clinical situation in which malaria-associated hypoglycaemia occurs. PMID- 2096011 TI - Intratesticular control of steroidogenesis. PMID- 2096010 TI - Detection of autoantibodies to recombinant human thyroid peroxidase by sensitive enzyme immunoassay. AB - Autoantibodies to thyroid peroxidase (TPO), the thyroid 'microsomal' antigen, are widely utilized in the diagnosis of human autoimmune thyroid disease. Crude human thyroid preparations of TPO are of differing potency, contain residual thyroglobulin (Tg) and other human membrane antigens, and are available in only limited amounts. Hence, immunoassays for anti-TPO are unstandardized and of variable sensitivity and specificity. We co-transfected the Chinese hamster ovary (CHO) cell line with a full-length human TPO cDNA expression plasmid. We selected a high expressing recombinant TPO positive cell population (CHO-TPO) by Northern blot analysis, then fluorescence laser flow cytometry using both human polyclonal and murine monoclonal anti-TPO antibodies. Solubilized 100,000 g membrane preparations from both CHO-TPO and CHO cells were used as antigens in a specific ELISA with CHO antigen serving as background control. In a selected series of known anti-TPO positive (n = 46) and negative (n = 73) sera there was a high correlation between ELISAs utilizing recombinant or natural-TPO antigen (r = 0.93). There appeared to be no difference in the affinity of high titre human anti-TPO for recombinant and natural-TPO antigen with both ELISAs able to detect 0.05 U/ml of anti-TPO activity (reference preparation NIBSC 66/387). These data predict a new era in standardized thyroid autoantibody testing utilizing recombinant antigen preparations. PMID- 2096012 TI - Screening tests for Cushing's syndrome. PMID- 2096013 TI - Actin-associated proteins in Dictyostelium discoideum. AB - The cellular slime mold Dictyostelium discoideum is becoming the premier system for the explication of the biochemical and cellular events that occur during motile processes. Proteins associated with the actin cytoskeleton, in particular, appear to play key roles in cellular responses to many external stimuli. This review summarizes our present understanding of the actin-associated proteins in Dictyostelium, including their in vitro activities and their structural and/or functional analogues in mammalian cells. PMID- 2096014 TI - Ponticulin, a developmentally-regulated plasma membrane glycoprotein, mediates actin binding and nucleation. AB - Ponticulin is a 17,000-dalton transmembrane glycoprotein that is involved in the binding and nucleation of actin filaments by Dictyostelium discoideum plasma membranes. The major actin-binding protein isolated from these membranes by F actin affinity chromatography, ponticulin also binds F-actin on blot overlays. The actin-binding activity of ponticulin in vitro is identical to that observed for purified plasma membranes: it resists extraction with 0.1 N NaOH, is sensitive to high salt concentrations, and is destroyed by heat, proteolysis, and thiol reduction and alkylation. A cytoplasmic domain of ponticulin mediates binding to actin because univalent antibody fragments directed against the cytoplasmic surface of this protein inhibit 96% of the actin-membrane binding in sedimentation assays. Antibody specific for ponticulin removes both ponticulin and the ability to reconstitute actin nucleation activity from detergent extracts of solubilized plasma membranes. Levels of plasma membrane ponticulin increase 2- to 3-fold during aggregation streaming, when cells adhere to each other and are highly motile. Although present throughout the plasma membrane, ponticulin is preferentially localized to some actin-rich membrane structures, including sites of cell-cell adhesion and arched regions of the plasma membrane reminiscent of the early stages of pseudopod formation. Ponticulin also is present but not obviously enriched at phagocytic cups of log-phase amebae. These results indicate that ponticulin may function in vivo to attach and nucleate actin filaments at the cytoplasmic surface of the plasma membrane. A 17,000-dalton analogue of ponticulin has been identified in human polymorphonuclear leukocyte plasma membranes by immunoblotting and immunofluorescence microscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096015 TI - Cell-cell adhesion and morphogenesis in Dictyostelium discoideum. AB - During development of Dictyostelium discoideum, cells acquire EDTA-resistant cell cell adhesion at the aggregation stage. The EDTA-resistant cell binding activity is associated with a cell surface glycoprotein of Mr 80,000 (gp80), which mediates cell-cell binding via homophilic interaction. Analysis of the structure of gp80 deduced from cDNA sequence reveals the presence of three internally homologous segments in the NH2-terminal domain, which also contains regions with homology to the neural cell adhesion molecule. Secondary structure predictions show an abundance of beta-structures and very few alpha-helices. This is confirmed by circular dichroism measurements. It is likely that the homologous segments are organized into globular structures, extended from the cell surface by a Pro-rich stalk domain. The cell binding activity of gp80 resides within the first globular repeat of the NH2-terminal domain and has been mapped to a 51 amino acid region between Val123 and Leu173. Synthetic oligopeptides corresponding to sequences within this region have been prepared and assayed for their ability to bind to cell surface gp80. Results lead to identification of the homophilic binding site to an octapeptide sequence within this region. Synthetic peptides containing this octapeptide sequence and univalent antibodies directed against this site block the formation of organized cell streams during aggregation. Although cell aggregates are eventually formed, most fail to undergo further development to give rise to slugs and fruiting bodies, indicating that cell-cell adhesion involving gp80 is an important step in normal morphogenesis. PMID- 2096016 TI - Quantification of transformation efficiency using a new method for clonal growth and selection of axenic Dictyostelium cells. AB - A new method for clonal growth of Dictyostelium axenic amoebae has been developed. Cells are plated in growth medium containing 1% ultra-low gelling temperature agarose. Cells grow normally in the agarose and form colonies up to several millimeters in diameter. When the colonies have grown to a sufficient size, they begin multicellular development. Pseudoplasmodia are formed, migrate to the surface of the agar, and then undergo fruiting body formation. Cells can be removed from the soft agarose colonies with a toothpick or by picking spores from the fruiting bodies. This method should be useful for drug, auxotrophic, and temperature selections where clonal maintenance of axenic colonies is important. This method has been used in combination with a selection for resistance to G418 to isolate independent colonies following DNA-mediated transformation. Several parameters in the calcium phosphate and electroporation transformation protocols have been optimized and the transformation frequency quantified. Independent transformed colonies are obtained at a frequency of 1 in 10(4) to 1 in 10(5) cells when integrating plasmids are introduced using calcium phosphate coprecipitation. The frequency is about tenfold higher when extrachromosomal shuttle vectors are introduced into cells. PMID- 2096017 TI - Nonsense suppression in Dictyostelium discoideum. AB - We describe the generation of Dictyostelium discoideum cell lines that carry different suppressor tRNA genes. These genes were constructed by primer-directed mutagenesis changing a tRNA(Trp)(CCA) gene from D. discoideum to a tRNA(Trp)(amber) gene and changing a tRNA(Glu)(UUC) gene from D. discoideum to a tRNA(Glu)(ochre) as well as a tRNA(Glu)(amber) gene. These genes were stably integrated into the D. discoideum genome together with a reporter gene. An actin 6::lacZ gene fusion carrying corresponding translational stop signals served as a reported. Active beta-galactosidase is expressed only in D. discoideum strains that contain, in addition to the reporter, a functional suppressor tRNA. Both amber suppressors are active in D. discoideum without interfering significantly with cell growth and development. We failed, however, to establish cell lines containing a functional tRNA(Glu)(ochre) suppressor. This may be due to the fact that nearly every message from D. discoideum known so far terminates with UAA. Therefore a tRNA capable of reading this termination codon may not be compatible with cell growth. PMID- 2096018 TI - Analysis of developmentally expressed antigens in Polysphondylium pallidum. AB - A series of monoclonal antibodies were previously raised against developing Polysphondylium pallidum cells. In this work, six of these antibodies have been used as probes to identify and characterize antigens regulated during development. Soluble and membrane fractions of P. pallidum cells at six stages of development or three stages of cyclic adenosine monophosphate (cAMP)-induced development were run in sodium dodecyl sulfate (SDS)-polyacrylamide gels and subjected to Western blot analysis. Three of the monoclonals, anti-Tp200, anti Tp423, and anti-Pg101, stain sorogen tips. Tp423 and Tp200 are membrane associated antigens; both are stable to urea extraction, and Tp200 remains in the membrane after NaOH extraction. Tp423 is present in starved cells but is more prominent in sorogens and particularly in cAMP-developed cells. In contrast, Tp200 is first detected in early to mid-aggregation and is more abundant late in development. Pg101, which is expressed as a gradient with its highest concentration in tips, first appears in tight aggregates but is much more abundant in sorogens; unlike the Tp antigens, Pg101 is not greatly induced in cAMP-developed cells. All three of these antigens undergo changes in apparent molecular weight at the tight aggregate or sorogen stage: The gel mobilities of Tp200 and Pg101 increase, whereas that of Tp423 decreases. In addition to the tip specific monoclonals, two monoclonals that stain all but the tips of sorogens have been used for analysis. One of these, anti-3D10Pnk stains most cells within secondary tips, whereas anti-3D10Dif does not. 3D10Dif is membrane associated; it is present very early in development, increasing two- to threefold through the sorogen stage and diminishing in late cAMP-developed cells. 3D10Pnk is a mostly soluble species first detected in late streaming. Anti-1c3, a sixth monoclonal, which stains nuclei uniformly throughout sorogens, is also developmentally expressed. 1c3 is mainly membrane associated and is expressed from late streaming through the sorogen stage. PMID- 2096019 TI - Regulation of the anterior-like cell state by ammonia in Dictyostelium discoideum. AB - Ammonia appears to be an important regulatory signal for several aspects of the Dictyostelium life cycle. The postulated role of ammonia in the determination of the prespore pathway in cells of the slug stage has led us to examine the effect of ammonia on the prestalk/prespore ratio of migrating slugs. In the presence of 10(-3) M ammonium chloride, the volume of the prestalk region decreases by 40.8%. The kinetics of the process make it unlikely that this is due to a shift in the differentiation pathway. A test of the hypothesis that the decrease in volume of the prestalk region is due to the conversion of prestalk cells to anterior-like cells shows that the percent of anterior-like cells in the posterior region increases by the amount predicted by the hypothesis. This suggests that ammonia may be the molecular signal, produced by the tip, that prevents anterior-like cells from chemotactically migrating to the tip and thereby becoming anterior cells. The effect of enzymatic removal of ammonia from vitally stained migrating slugs is the appearance of a series of dark stripes beginning at the posterior end and progressing forward. We interpret this as a result of progressive removal of anterior-like cells from tip dominance and essentially as the formation of new potential tips. Indeed, in a few cases one or even two of the stripes separate from the posterior of the cell mass and form small fruiting bodies. We consider the phenomenon of stripe formation further evidence that the tip acts on anterior like cells through ammonia. PMID- 2096020 TI - Formation of the Dictyostelium spore coat. AB - The spore coat forms as a rigid extracellular wall around each spore cell during culmination. Coats purified from germinated spores contain multiple protein species and an approximately equal mass of polysaccharide, consisting mostly of cellulose and a galactose/N-acetylgalactosamine polysaccharide (GPS). All but the cellulose are prepackaged during prespore cell differentiation in a regulated secretory compartment, the prespore vesicle. The morphology of this compartment resembles an anastomosing, tubular network rather than a spherical vesicle. The molecules of the prespore vesicles are not uniformly mixed but are segregated into partially overlapping domains. Although lysosomal enzymes have been found in the prespore vesicle, this compartment does not function as a lysosome because it is not acidic, and a common antigen associated with acid hydrolases is found in another, acidic vesicle population. All the prespore vesicle profiles disappear at the time of appearance of their contents outside of the cell; this constitutes an early stage in spore coat formation, which can be detected both by microscopy and flow cytometry. As an electron-dense layer, the future outer layer of the coat, condenses, cellulose can be found and is located immediately beneath this outer layer. Certain proteins and the GPS become associated with either the outer or inner layers surrounding this middle cellulose layer. Assembly of the inner and outer layers occurs in part from a pool of glycoproteins that is shared between spores, and unincorporated molecules loosely reside in the interspore matrix, a location from which they can be easily washed away. When the glycosylation of several major protein species is disrupted by mutation, the coat is assembled, but differences are found in its porosity and the extractibility of certain proteins. In addition, the retention or loss of proteolytic fragments in the mutants indicates regions of spore coat proteins that are required for association with the coat. Comparative examination of the macrocyst demonstrates that patterns of molecular distributions are not conserved between the macrocyst and spore coats. Thus spore coat assembly is characterized by highly specific intermolecular interactions, leading to saturable associations of individual glycoproteins with specific layers and the exclusion of excess copies to the interspore space. PMID- 2096021 TI - Management of cataracts. PMID- 2096022 TI - Contact sensitization of mice to nickel sulphate and potassium dichromate. AB - The ability of nickel sulphate and potassium dichromate to induce contact sensitization in mice has been investigated. Topical exposure of mice to 0.5% potassium dichromate in dimethylsulphoxide (DMSO) under occlusion resulted in specific contact sensitization in each of 7 experiments. Although sensitization to nickel sulphate under the same conditions was weak and somewhat variable, evidence for significant levels of contact allergy was obtained in 4 of 7 experiments. In addition, repeated topical application of both nickel sulphate and potassium dichromate in DMSO was found to result in the induction of lymphocyte proliferative responses in lymph nodes draining the site of exposure. These data indicate that epicutaneous exposure to both metal salts may cause specific contact sensitization in mice. PMID- 2096023 TI - Inhibitory effect of zinc oxide on contact allergy due to colophony. AB - Contact allergy to a wound dressing with an adhesive mass consisting of colophony, zinc oxide and rubber (Mezinc) was studied in 179 patients with a history of eczema. 12 patients were found to be allergic to colophony, whereas only 4 of these patients also showed a positive patch test reaction to the wound dressing. 14 patients with verified moderate contact allergy to colophony were patch tested with adhesive mass (10%), Portuguese colophony (10%), zinc oxide (10%), purified resin acids (10%), and Portuguese colophony (10%), in combination with zinc oxide. Only 3 patients reacted to the adhesive mass, whereas all patients showed a positive patch test reaction to Portuguese colophony. A combination of zinc oxide (10%) with Portuguese colophony (10%) provoked a positive patch test reaction in only 5 of these 14 patients. An allergic reaction to abietic acid (90-95% purity) was found in 7 patients and to neoabietic acid (99 + %) in 3 patients, whereas no reactions to dehydroabietic (99 + %), isopimaric (99 + %) or levopimaric acids (98 + %) were found. PMID- 2096024 TI - Contact allergy due to colophony (VII). Sensitizing studies with oxidation products of abietic and related acids. AB - 9 oxidation products of abietic acid, dehydroabietic acid, and levopimaric acid were prepared synthetically to determine their sensitizing potential in guinea pigs. It was found that compounds with epoxy and peroxo groups in rings A and B had a notable sensitizing potential. The same result was found with 7-oxode hydroabietic acid identified earlier in rosin (3) and a polar fraction obtained from commercial abietic acid, suggesting the presence of still unidentified oxidation products. Hydroxylation of rings A or B, or conversion to the methyl esters, considerably decreases the sensitizing potential. A model is presented underlining the importance of hydrophobic and polar domains, in addition to chemically reactive groupings, in the allergen. Insertion into the lipid bilayer may play an important role in contact sensitivity. PMID- 2096025 TI - Detection of rosin (colophony) components in technical products using an HPLC technique. AB - A method for detection of rosin (colophony) in technical products has been developed. The technique, using HPLC, is based on the analysis of abietic acid and dehydroabietic acid, major components of rosin. In the procedure described in this paper, the limit of detection was 0.001% for abietic acid and 0.015% for dehydroabietic acid. An average recovery of 88.9% for abietic acid and 88.2% for dehydroabietic acid was obtained. The lowest detectable amount of abietic acid (0.001%) corresponds to a content of 0.003% unmodified rosin in the product, assuming that the resin acid content in rosin is 90%, of which 30-50% is abietic acid. This is an acceptable limit compared to the reactivity in patients with known allergy to rosin. Technical products for analysis were supplied by different Swedish manufacturers, who also gave the approximate content of rosin in the various products. The content of rosin determined in the products was in accordance with the contents given by the manufacturers. PMID- 2096026 TI - Tikka dermatitis. PMID- 2096027 TI - Allergic contact conjunctivitis from synthetic detergents in a nurse. PMID- 2096028 TI - Sensitization to nickel, cobalt and chromium in surgical patients. PMID- 2096029 TI - Cinnamic aldehyde 2% pet. is irritant on patch testing. PMID- 2096030 TI - Pitfalls in patch testing: problems with rather than from Kathon CG. PMID- 2096031 TI - Family reunification. PMID- 2096032 TI - Residential placement of youth: pathways, alternatives and unresolved issues. PMID- 2096033 TI - [Cancer of the hypopharynx and cervical esophagus. Role and limits of the surgical treatment]. AB - From 1975 to 1988, we observed 169 patients with a carcinoma of the cervical esophagus, 85 with a carcinoma involving the hypopharynx and the cervical esophagus, and 27 with a carcinoma of the cervical esophagus occurring after laryngectomy for laryngeal carcinoma. The average age was 57.5 years (41-73). Exploration was surgical for 167 patients (operability ratio 59.5%), and the lesion was resected in 152 cases (resectability ratio 81.1%). Resection was complete in 129 patients (84.5%) and palliative in 23 (14.5%). A laryngopharyngoesophagectomy involving the cervical esophagus and requiring the transplantation of a free intestinal loop was performed in 33 cases, with an operative mortality rate of 6.1%. Pharyngolaryngectomy with total esophagectomy was performed in 101 patients, and the digestive tract was reconstructed by means of pharyngogastrostomy or pharyngocolostomy (respectively 85 and 16 cases) with an operative mortality rate of 12.9% and 18.3%, respectively. Complete esophagectomy without laryngectomy was performed for 18 patients with carcinoma of the distal cervical esophagus who refused laryngectomy, the hospital mortality rate being of 5.5%. The actuarial survival rate after 5 years (not including operative mortality) was 15.8%. Better results were achieved after complete resection for carcinoma of the hypopharynx than for carcinoma of the cerebral esophagus. The actuarial survival rates after 2 and 5 years were 59% vs. 26% and 43% vs. 17% respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096034 TI - [Use of the calvarium for bone grafting in cranio-maxillo-facial surgery]. AB - Bone grafts's traditional donor sites in cranio-maxillo-facial surgery have been for many years and are still in some occasions the ribs, iliac crest and tibia. Bone grafts taken from the calvaria have been used by some surgeons in the past but its wide acceptance was only achieved after Paul Tessier had reported his own experience. The calvaria is composed of inner and outer tables that encloses a layer of cancellous bone called the diploe. A high degree of variability exist with respect to skull thickness. Nevertheless parietal bones is the preferable site for the harvesting of the graft. The embryonic origin of the cranium should be responsible for greater survival of the graft. Membranous bone would maintain its volume to a greater extent than endochondral bone when autografted in the cranio-facial region. However this remains controversial. Two techniques can be used for the harvesting of a calvarial bone grafts. A split thickness calvarial graft involves removal of the outer table while leaving the inner layer in place. Its main disadvantage is the relatively thinness of the bone transferred. A full thickness segment of skull involves the cranium cavity be entered. A half of the graft can be split along the diploe space and returned to fill the donor site. The other half is used for reconstruction. It is a more complicated procedure. Cranial grafts have been used in the following cases. Correction of contour defect of the forehead and zygomatic bones, orbital floor reconstruction, restoration of the nasal bridge, bone grafting of the maxilla and mandibule. The advantages are the following: the donor and recipient sites are in adjacent surgical fields, the donor site scar is hidden in the scalp, morbidity associated with removing the graft is almost inexistent. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096035 TI - [Value of early decompression in compartment syndrome of the burnt hand]. AB - Our experience with over one hundred burned hands has shown that the compartment syndrome is a frequent occurrence in the hand and fingers. It is often underestimated because clinical diagnosis is difficult and an infra-clinical ischaemia may exist although the pulse is present. We believe it is important to carry out systematically Whiteside's method of investigating pressure in the compartments of the hand. When pressure exceeds 40 mm Hg the interosseous compartments and sometimes the digital canals or even the antebrachial compartment should be opened. This simple technique followed by early excision and graft and intensive rehabilitation has in our experience transformed the prognosis of burned hands. PMID- 2096036 TI - [Cutaneous expansion in burns sequelae]. AB - This technique of skin expansion with inflatable balloons has rapidly become generally used since Neuman's and Radovan's work. It offers new prospects for the treatment of the sequellae of burns as it allows increasing the surfaces of the remaining unaffected skin and using them to cover the excision of scar lesions by local or remote flaps. Experience with more than 500 implanted balloons is assessed, demonstrating very satisfactory general results in spite of a still too high number of complications, which increasingly refined techniques aim at reducing. PMID- 2096037 TI - [Surgical indications of hyperbaric oxygen therapy]. AB - Beside clostridial myonecrosis surgical utilization of hyperbaric oxygen remain unprecise. After review of literature, analysis of their experience, the authors define: principles and effects of hyperbaric oxygen, his position with regard to surgical intervention, its surgical utilizations: unquestionable (non clostridial and clostridial gas gangrene), relative (aerobic cellulitis, diabetic arterial disease), preventive. PMID- 2096038 TI - [Is the excision surgery of bronchial cancer in patients over 70 years of age justified?]. AB - The retrospective analysis of 331 files relating to primary bronchial cancer shows that 30% of the patients are 70 years old or over. This patient group is compared to younger subjects who were operated during the same period. For this surgical series, the disease studied is the same whichever the age (detection conditions, excision types, TNM classification). Mortality for excision is comparable (5.1% vs 8.2%), but the type of mortal complications differs according to the age. Our analysis allows isolating two factors of risk (cardiovascular defects and obstructive chronic respiratory failure). Provided that a pre operation rigorous selection of the patients over 70 years has been made, pneumonectomy does not seem more serious than lobectomy (mortality 3.7% vs 10.3%). For identical stages, remote survival after excision can be compared to that of operated patients under 70 years old. Excision beyond 70 years old seems justified provided that: a selection of patients, from which subjects having major defects (cardiovascular and respiratory) should be excluded, is carried out by appreciating physiological age and not actual age, a pre-operation respiratory preparation is performed, a careful operating technique which allows avoiding surgical complications is used, a peri-operating assistance is provided. PMID- 2096039 TI - [Laryngotracheal stenosis in children. Current aspects of the surgical treatment and prevention]. AB - In the past 6 years, 40 children underwent surgery for laryngotracheal stenosis; 32 by the external approach, 8 by endoscopic CO2 laser. Twenty-seven children (67%) were less than 5 years old at the moment of treatment and 80% of the stenoses (n = 32) corresponded to an etiology that is secondary to endotracheal intubation and/or tracheotomy. By grading the stenoses according to the amount of narrowing of the lumen, the authors emphasize the interest of conservative treatment (endoscopic) for grade I (less than 70%, n = 8), and treatment by external surgical methods for grade II (70%-90%, n = 13), grade III (90%-99%, n = 14), and grade IV (total obstruction, n = 5). At this time, the most commonly used technique is laryngotracheoplasty with costal cartilage interposition. In this series, 88% of the patients were successfully decannulated. As for the treatment of stenosis in infants, the authors describe their recent experience of laryngotracheofissure in 7 patients as an alternative to either tracheotomy in cases of difficult extubation or laryngotracheoplasty when the child is underweight. PMID- 2096040 TI - [Antibiotic prophylaxis in abdominal surgery]. AB - In order to compare the efficacy of antibiotic therapy using Cefalozin or Cefotaxime, 3,137 patients operated with an abdominal approach were included into a multidepartmental prospective study by lot. The patients were distributed into 4 levels according to the degree of intraoperative contamination and to the risk factors they presented. The patients in each level were distributed by lot into three treatment groups: 1) Cefalozin, 2) Cefotaxime, 3) no treatment. The antibiotics were delivered perioperatively in 3 doses of 1 g every eight hours. The patients having had colic surgery or operated for peritonitis were excluded from the study. The number of intestinal wall abscesses was significantly lower in the treated groups, except in level 3 (contaminated surgery). The percentage of postoperative peritonitis was twice lower in the treated groups than in the control group. There was no difference between the treated groups. The patients included in the treated groups were given significantly less antibiotics than the patients of the control group. As far as costs are concerned, antibiotic prophylaxis with Cefalozin is effective in all procedures of abdominal surgery in which the degree of contamination by anaerobes is low. PMID- 2096041 TI - [Homeopathy for the restoration of transit after abdominal surgery]. AB - Six hundred patients were alloted to one of 4 groups and given: 1) no treatment, 2) a homeopathic treatment (Opium and Raphanus), 3) Opium + a placebo, 4) two placebos. This work does not confirm the role of either Opium or Raphanus in the restoration of transit following abdominal surgery. PMID- 2096042 TI - [Manual or mechanical right colon anastomosis?]. AB - One hundred and forty patients were included in a prospective, randomized, multidepartmental study in order to compare four manual and on mechanical type of ileocolic anastomoses after right hemicolectomy for cancer. The study was designed as a pragmatic trial as defined by Schwartd. The main criterion of assessment was the anastomotic dehiscence judged with clinical criteria or a systematic follow-through with Gastrograffine on the tenth day postoperatively. All groups were similar except for a lower incidence of intraoperative septic factors for the group treated with mechanical anastomoses. The results show that the mechanical anastomosis produces fewer anastomotic dehiscences than all the other procedures except the terminolateral anastomosis with separate stitches using a slow-absorption suture material. Although it is about ten times as expensive as manual anastomosis, we suggest performing a mechanical ileocolic anastomosis after right hemicolectomy for cancer or, failing that, a manual terminolateral anastomosis with separate stitches. PMID- 2096043 TI - [Extend of colonic excision in the curative treatment of cancers of the left colon. Left or segmental hemicolectomy? A controlled prospective multicenter study]. AB - The ideal extent of colic excision in the curative treatment of left colic cancers has not yet been defined. The aim of this study is to compare the survival rates following left hemicolectomy and segmental colectomy. Over a period of 5 years from 1980 to 1985, 270 consecutive patients with cancer of the left colon without visceral metastases nor invasion of neighboring organs were included in the study. Survival at 5 years was the main criterion of assessment, with mortality and morbidity being the secondary criteria. 10 patients were excluded a posteriori. Out of the remaining 260 patients, 131 were operated with left hemicolectomy and 129 with segmental colectomy. Both groups were comparable as regards age; sex, risk factors (diabetes, renal failure), radiation therapy, antimitotics, procedure of anastomosis (hand or machine), protective colostomy, size of the tumor, and Dukes' stage. Only the length of the colon resected proximel to the tumor was greater in left hemicolectomy. 16% of the patients had a Dukes A adenocarcinoma. Postoperative mortality was higher after left hemicolectomy (6.1%) than after segmental colectomy (2.3%), but not significantly. Morbidity was similar. The survival rate at 5 years, including immediate deaths, was 64.8% after left hemicolectomy and 65.8% after segmental colectomy. Both survival charts could be strictly superimposed without significant differences. Left hemicolectomy therefore produced results that were comparable to those of segmental colectomy. PMID- 2096044 TI - [Colorectal anastomosis: manual or mechanical? A controlled multicenter study]. AB - 272 patients underwent randomly 133 hand sewn anastomosis and 139 stapled anastomosis (159 proximal and 119 distal) after elective colorectal resection for 194 carcinomas, and 78 sigmoid diverticulosis and benign tumors. Both groups were comparable with regard to mortality (3.3 p. cent), wound abcesses (3 p. cent) extra abdominal post operative complications (20 p. cent). There were however more reoperations in the stapled group (10 versus 6), and also more low intestinal anastomotic bleeding (9 versus 5). Stapled anastomosis were associated with less clinical fistulas (8 p. cent versus 12 p. cent) and only after low colorectal anastomosis (9 p. cent versus 20 p. cent). Stapling devices decrease the duration of the anastomosis by 8 mn, but this gained time does not influence the total duration of the operation. These advantages must be weighed against the risks inherent to their uses, mishaps (14 p. cent), hemorrhages (6.5 p. cent), strictures (8 p. cent), and their higher cost (15 times as much). PMID- 2096045 TI - [Villous tumors of the rectum. 50 cases treated surgically]. AB - The authors report a study of 50 patients who underwent surgery for a villous adenoma between 1978 and 1988 (29 men and 21 women). Mean age was 70 years old. 84% of the lesions were sessile. They ranged from 1 to 15 centimeters in size. They were associated 12 times with colon adenomas and 3 times with adenocarcinomas. All these lesions were biopsied preoperatively. Removal was performed: in 38% of cases vie a transanal approach in 38% of cases by colorectal resection vie an abdominal approach in 12% of cases by rectal amputation vie both an abdominal and perineal approach, in 12% of cases by Kraske's procedure. 22 adenocarcinomas and 28 benign lesions were discovered. 2 patients died in the early post-operative course after colorectal resection performed vie an abdominal approach. At long term (minimum of 2 years) there were 5 complications and 9 recurrences, the later occurring after tumorectomies. It is essential to know the lesions histologic characteristics in order to administer appropriate therapy, but this is not only possible to determine precisely before excision. Even biopsy specimens may miss the malignant portion of a lesion. Only complete pathological examination of the tumor can establish the diagnosis of a malignancy. Surgery remains the principal method of treatment of these lesions because it permits complete histologie examination and properly adapted management: simple removal for benign tumors or those with malignant degeneration in situ, wide excision for invasive tumors. PMID- 2096046 TI - [Indications for surgical treatment of fractures of the acetabulum]. AB - The indications for surgery in fractures of the acetabulum within 3 weeks from the accident are currently based on 2 main factors: 1) post-traumatic articular incongruence doubtlessly is the cause of traumatic coxitis: 2) however, it has been proved that fractures with partial post-traumatic incongruence that have not been treated may produce very good results. The current problem is that it is impossible to assess the degree of incongruence that can be tolerated to avoid surgery and guarantee good long-term results. Computers will maybe help to solve this problem. The indications are currently based on the approximate assessment of congruence on the basis of 3 plain radiographs, tomography and CT. Osteonecrosis of the femoral head is much less frequent than it is said to be, and most often actually consists in the wear of the femoral head on a non-reduced line of fracture, whether or not the patient has been operated. PMID- 2096047 TI - [Current role of decortication in problems of bone healing]. AB - The authors present the results of 101 osteo-periostal decortications. This technique was used in 72 cases of aseptic non-union, 15 cases of infected non union and 14 cases with malunion. Stable fixation was carried out using a plate or an external Judet fixator. An autologous cancellous or cortico-cancellous bone graft was added in 12 cases. Union was achieved in 98 of 101 patients after an average of 45 days to 4 months, depending on the localisation and the etiology involved. The 3 failures were due to technical errors or presence of an unfilled bone defect. Osteoperiostal decortication is a reliable and reproductible solution to many problems of malunion or non-union. We consider bone grafting to be necessary only in patients with a major bone defect. PMID- 2096048 TI - [Taloscaphoid arthrodesis and foot statics]. AB - The talo-navicular joint takes a part in both talocalcaneal and midtarsal joints's motion. Its arthrodesis produces all but suppression of subtalar joint motion. If there is surgical indication for deformed but flexible foot, better than a standard resectional subtalar arthrodesis, talo-navicular arthrodesis, with easy technique, is successful to maintain correction in right position, specially for valgus flat foot. PMID- 2096049 TI - [Therapeutic problems caused by rupture of large hepatic adenoma with central location. Apropos of 3 cases]. AB - We report three cases of young female patients (26, 30, 36 years) with intraperitoneal hemorrhage associated with a rupture of a liver cell adenoma. Their topography was central or with central extension. Three patients had taken oral contraceptives, for a period of 10 years, before diagnosis in two cases and for only three weeks in the remaining patient. The diagnosis of hemoperitoneum from a liver tumor was established on initial symptoms and ultra sonographic examination. Angiography and CT were the most valuable investigations. The control of hemorrhage was obtained by hepatic artery ligation (2 cases) and angiographic embolization (1 case). We observed one patient with liver adenomatosis, uncommon lesion consisting of numerous adenomas in an otherwise normal hepatic parenchyma. In emergency major hepatic resection for an adenoma, in central localization, is too a high risk procedure for a benign tumor. Control of hemorrhage should be the aim of treatment, best achieved by alternative treatment, such as hepatic artery ligation of angiographic embolization, highly effective in our experience. Resection may be delayed for a residual tumor. PMID- 2096051 TI - [Extracorporeal shock wave lithotripsy in the treatment of biliary stones]. AB - From Sep. 1988 to Dec. 1989, 163 patients with gallstones and 7 with choledocholith were treated by biliary extracorporeal shock wave lithotripsy (ESWL). After lithotripsy, ursodeoxycholic acid was administered in 74 patients, and self-made lithoexpulsive in 44 patients. The remaining 52 patients were given both ursodeoxycholic acid and lithoexpulsive. The total rate of stone fragmentation was 97.6%. One hundred and twenty patients were followed up after ESWL. Biliary stones disappeared in 26.6% of the patients within one month after ESWL, in 33.3% within one to three months, and in 36.6% within six to eight months. There were no severe complications. 10.1 percent of the patients had abdominal discomfort during the procedure of ESWL, and cutaneous petechiae were found in 12.2% of the patients. Other complications included biliary colic in 6, jaundice in 2, and hematuria in 2. Serum enzymology and chest X-ray remained unchanged after ESWL. PMID- 2096050 TI - [Knee prosthesis in 1990. Apropos of a 15 years' experience]. AB - Knee prostheses have been greatly refined over the past ten years. A range of prostheses with various designs are currently used. On the basis of their 15-year experience, the authors assess the role of the various prostheses. Among partial prostheses, the femoropatellar prosthesed have a restricted place and are reserved for isolate degenerative diseases of the femoropatellar joint without femorotibial involvement: 34 such prostheses have been used by the authors and the department of professor J.H. Aubriot in Caen. About 75% of the results are satisfactory, with a follow-up in time of more than 8 years in 6 of these cases. Single-compartment prostheses are used in degenerative disease on an angular deviation, condylar necrosis or post-traumatic lesions, as far as one compartment only is affected. The authors have inserted 115 "Lotus" uni-compartment prostheses at Saint-Louis hospital. 75.6% of these have very good or good results maintained in time, as 72% of the 32 prostheses still produce satisfactory results after 5 years or more. The greatest progress was made above all for total prostheses replacing all the compartments of the knee. Hinge prostheses now have only rare indications as first-intention prostheses due to the immediate vital risks and to the high percentage of suppuration and long-term loosening. Sliding prostheses have taken an increasingly dominant place. The authors used Insall's total condylar prostheses, which do not preserve the posterior cruciate ligament, until 1983. 45 prostheses were followed up for 1 to 10 years, showing 71% of very good or good results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096052 TI - [Clinical study of lung injury in acute pancreatitis]. AB - Lung injury is a common and severe complication in acute pancreatitis. The pathogenesis of which has not been completely understood. To explore the mechanism of lung injury, ST and FFA and PLA in bronchoalveolar perfusate, FFA and PLA in blood were measured; clinical symptoms and chest film were analysed; blood gas analysis was performed. The results indicated that lung injury mostly occurs in ABNP and less in AEP. Pulmonary edema and atelectasis are essential changes of lung injury. It is believed that FFA is an important factor responsible for pulmonary edema. PLA, which plays the most important role in lung injury, not only results in atelectasis by degradating the SA in alveolar, but also induces pulmonary edema. The main reason for the increase of ST is the degradation of SA in alveolar. The levels of FFA and PLA in the blood may indicate the severity of acute pancreatitis. However, it remains unknown whether the synthesis of SA in patient with acute pancreatitis is inhibited. PMID- 2096053 TI - [Cystic duct anomalies found by ERCP and their clinical implications]. AB - The site of confluence of cystic duct (CD) and common bile duct (CBD) was surveyed by ERCP in 1100 cases. Abnormal confluence was found in 65 (5.9%). There were three types of variations: (1) Low-sited confluence in 54/65 (83%), in which the length of CBD was significantly shorter than that of common hepatic duct (CHD). (2) Very low-sited confluence in 9/65 (13.8%), in which CD joined CBD at the level of CBD sphincter (3) High-sited confluence in 2/65 (3.2%), in which CD joined right hepatic duct or the beginning of CHD. The clinical implications of these anatomical variations are discussed. PMID- 2096054 TI - [Value of 5-hour glucose tolerance test in the diagnosis of insulinoma]. AB - We probed into the role of glucose tolerance test (GTT) in the diagnosis of insulinoma. According to the test results, 63 cases of insulinoma fell into four types. Insulinomas failed to respond normally to the stimulus of glucose and the response of insulinoma was nonspecific within 120 minutes after glucose load. The peaks of glucose tolerance curves were delayed and hypoglycemia was the rule before and 300 minutes after glucose load. GTT results of the same patient were varied from time to time. The results suggest that five-hour GTT is superior to three-hour GTT in the diagnosis of insulinoma. PMID- 2096055 TI - [Surgical treatment of multiple primary carcinoma of the alimentary tract: report of 15 cases]. AB - From March 1964 to December 1986, 26 cases of multiple primary carcinomas were treated in our clinic. Among them 15 cases (57.7%) were multiple primary carcinomas of the alimentary tract including 9 cases of synchronous carcinomas and 6 cases of metachronous carcinomas. All the cases were confirmed by operation and pathological examination. There were 12 males and 3 females. Their ages ranged from 33 to 68 years and most (86.7%) were between 50 and 68 years. The combination of involved organs were mainly esophagus and gastric cardia (11 cases) and colon and gall bladder (2 cases). The pathological combinations were squamous carcinoma and adenocarcinoma (53.3%), adenocarcinoma and adenocarcinoma (26.7%), and squamous carcinoma and carcinoma in situ (6.7%). The follow-up data showed that treatment results of multiple carcinomas of the alimentary tract were poor. PMID- 2096056 TI - [Traumatic respiratory distress syndrome on plateau: diagnosis and treatment]. AB - Twenty-seven adult patients, living at plateau, developed acute respiratory syndrome after severe trauma or major operation, were reported. Seven of them died. The clinical pictures were also of severe air-hunger, cyanosis and hypoxemia associated with diffusive interstitial edema of lungs, while the mean values of blood gases were much less compared with those of patients on plain, being P-a O2 33 mm Hg, Sat. O2 71%, PaCO2 31 mmHg, A-aDO2 426 mm Hg. The diagnostic points of ARDS of patient on plateau have been suggested and the urgent requirement of management for these patients on plateau has been emphasized and described. PMID- 2096058 TI - [Indications and complications of omental transplantation to the spinal cord]. AB - From 1984 to 1986, 56 cases with traumatic paraplegia were treated by transplanting the intact omentum to the injured spinal cord. All patients were followed up 1 to 4 years. In these patients, the sensory level descended variously in 80.0%, muscular power increased in different degrees in 60.9% and sphincter function improved in 76.8%. The indications of this operation are incomplete paraplegia with EMG showing nervous activity. Satisfactory effects can be expected in injuries of the thoracolumbar segments and in mild contusion spinal cord. Fistula with of leak of cerebrospinal fluid, is a severe complication, it may be prevented by suturing the omentum to the dura, complete hemostasis, and tight muscular suturing. The absorb function of the omentum also helps in its prevention. PMID- 2096057 TI - [Changes in platelet aggregation, TXB2 and 6-keto-PGF1 alpha in surgical shock]. AB - Platelet aggregation rate (PAR), plasma concentration of TXB2 and 6-Keto-PGF1 alpha were measured in 26 patients with shock (hypovolumic shock 10 and septic shock 16) and 10 controls. PAR, plasma TXB2 and 6-Keto-PGF1 alpha were increased during shock, with TXB2 increased more significantly than 6-Keto-PGF1 alpha, accordingly the TXB2/6-Keto-PGF1 alpha ratio were raised during shock, especially in the septic cases. PAR, plasma TXB2 and 6-Keto-PGF1 alpha will decrease while shock become subsiding, and elevate while shock become irreversible. As a rule, the change of PAR is parallel with the concentration of plasma TXB2. The speed of platelet aggregation and plasma TXB2 concentration were higher in eleven mortal cases. PMID- 2096059 TI - [The unilateral axial dynamic fixator study of its biomechanical property and clinical application]. AB - The home made UADF after Bastiani's pattern was mechanically tested in our lab on fracture of cadaveric femurs. For comparison, the same test was also carried out with conventional semicircular external fixator. The results showed that the rigidity and stability of fixation closely related with the diameter of the bone pin used. The diameter of the treated pins used in UADF was one time larger than that of the round pin used in conventional semicircular external fixator. The compression rigidity of the former frame was 3.5 times stronger than that of the latter one; the extent of displacement of the fragments happened in the former frame was much less than that occurred in the latter one. Clinical Application of UADF. on fracture of tibia and fibula in 31, of femur in 8, knee arthrodesis and osteotomy of tibia and fibula one in each, brought bony healing on successfully. It is apparent that the UADF is multifunctional, universal and adaptable in use, leading to success. PMID- 2096060 TI - [Surgical treatment of chronic constrictive pericarditis]. AB - From April, 1969 to December, 1988, partial pericardiectomy was performed in 78 patients with chronic constrictive pericarditis. The long-term follow-up study in 60 patients showed a satisfactory functional result. The authors considers that the median sternotomy is a better approach, the effectiveness of operation should be gauzed by dropping the vena cave pressure below 140 mmH2O, resection of pericardium from left to right is logical, and rational use of cardiotonic agents is important. PMID- 2096061 TI - [Ultrasonographic diagnosis of achalasia: report of 27 cases]. AB - In this paper the ultrasonographic findings of 27 cases with achalasia are reported. The result of ultrasonic diagnosis of 27 cases were all in conformance with the final diagnosis. The ultrasonographic features of achalasia are described detail. The usefulness and advantages of ultrasonography in the diagnosis and differential diagnosis for achalasia are discussed. PMID- 2096063 TI - [Diagnosis and treatment of bladder transitional cell carcinoma in 19 hospitals in Tianjing]. AB - From 1978 to 1987, 1108 cases of bladder tumors were admitted in 19 hospitals in Tianjing, among which 91.8% (997 cases) was bladder transitional cell carcinoma and accounted for 10% of all the inpatients admitted at the urology department during the same period. The conditions of the diagnosis and treatment of the bladder transitional carcinoma are analysed, the present problems and the improvement opinions are suggested in the present report. PMID- 2096062 TI - [Experience in 712 cases of tuberculosis of chest wall by surgical treatment]. AB - From 1976 to 1987, 712 cases of tuberculosis of chest wall were treated surgically in our hospital. The primary cure rate was 97.2% (692/712). In 20 cases, the disease recurred and were cured after the second operations. The Diagnostic criteria, operative methods and causes of recurrence are discussed. PMID- 2096064 TI - [Comparison of renal carcinoma in two periods: analysis of 129 cases]. AB - From 1954 to 1988, 129 patients of renal carcinoma were admitted to our hospital. The 129 cases were divided into two groups for comparison and analysis. Since 1980, examinations of model B ultrasound, CT scanning and arteriography have been popularly used in the diagnosis, many cases of renal cell carcinoma can be early found and treated, so the prognosis has been markedly improved. In this group, the total 5-year survival rate was risen from 27.7% to the 58.8%. PMID- 2096065 TI - [Indirect lymphography for diagnosis of limb lymphedema]. AB - Twenty patients with various forms of lymphedema were studied by indirect lymphography. Isovist (Schering AG, Berlin) used for intradermal infusion is a new non-ionic, water-soluble, dimeric contrast media. It has following advantages: ideal iso-osmolarity, lowest physical-chemicotoxicity, and excellent tissue tolerance. Simultaneous indirect lymphography was recommended. Characteristic patterns of lymphatics were demonstrated. The newly developed Isovist allows visualization of initial lymphatics by intradermal infusion. However they are not displayed with direct lymphography unless in the presence of valvular insufficiency. It can be performed within 30 minutes. No chemical injury to lymphatics would happen so that this procedure could performed repeatedly. PMID- 2096066 TI - [A lingulate valve formed from full layer of the jejunum in Roux-en-Y choledocho jejunostomy and its effect against regurgitation of intestinal contents]. AB - A lingulal valve formed from full layer of the jejunum designed to work against regurgitation of intestinal contents was reported. Animal experiment and the observation on fresh bodies documented that it could prevent regurgitation at the pressure of 2.94 kPa (300 mmH2O). The valve-plasty was added to Roux-en-Y choledocho (pancreatico)-jejunostomy in ten cases with satisfactory results. The procedure is not technically difficult, and long term follow-up found no severe complications. PMID- 2096067 TI - [Promoting effect of L-dopa on experimental fracture healing]. AB - This study was planned to investigate the effect of oral administration of L Dopa, made in China, on fracture healing and to look into its activity or metabolic influence on biomechanical healing process. Both the tibia and fibula of left leg of 185 Wistar rats were manually fractured, but left alone without fixation, and were treated for 15 days. For the experimental group of animals, L Dopa in suspension, 0.4 gm/kg BW, was given daily; for the control one, only the same amount of saline solution. 12 to 24 hours following intraperitoneal injection of radioisotope tracers, 35S-sodium sulfate and 45Ca-calcium chloride non-carrier solution, were used. The animals in group were put to death at the 5 10 15 20 30- and 40-th day respectively after fracture. The fracture specimens were taken and processed for examination and quantitative assessment. The data showed that the amount of sulphur in the primary callus was increasing up to the peak on the tenth day; it was greater, statistically significant, in the test group (0.19 +/- 0.05 DPM%) than in the control one (0.13 +/- 0.05 DPM%). They showed too that the amount of calcium incorporated in the callus was also increasing up to a top point but at the 15-th day; it was as well greatly, statistically significant in the test group (4.50 +/- 1.16 DPM%) than in the control one (2.65 +/- 1.90 DPM%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096068 TI - [Experimental study of multiple organ injuries after high-velocity missiles]. AB - Multiple organ injuries after high-velocity missiles shot were studied on the 8 pigs. The experimental results showed that (1) more than two organs (the maximum six organs) wounded could be seen in all the pigs; (2) the injuries were characterized by hemorrhage, tissue rupture and hematoma, etc., the pathologic changes were local edema and necrosis; (3) the marked increase of LPO on the vital organs indicates that multiple organ injuries can also occur at the molecular level; (4) they are due to direct effects of pressure waves and not to shock or infection. PMID- 2096069 TI - [A comparative experimental study of side-to-side and end-to-side mesocaval shunt]. AB - In this study, the side-to-side (MCS-SS) and end-to-side (MCS-ES) mesocaval shunt were performed in two groups of thioacetamide (TAA)-induced cirrhosis of rats. The anastomotic stoma was made equal to the calibre of mesenteric veins. It was found that the portal vein pressure after MCS-SS was lower than that after MCS-ES owing to the more effective drainage of both extra- and intrahepatic portal blood flow. It was also found that with MCS-SS, some inflow from the superior mesenteric vein was reserved to irrigate the liver and the content of insulin in the portal vein was not affected. The authors came to the conclusion that MCS-SS was superior to MCS-ES for less likely causing post-shunt encephalopathy and the deterioration of hepatic function. PMID- 2096070 TI - [Experimental study of healing process of anastomosis after "tunnel" esophagogastrostomy]. AB - The "Tunnel" esophagogastrostromy has been clinically proven to be effective in reducing the postoperative anastomotic leakage. An experimental study was carried out in 28 dogs to compare the healing process of "Tunnel" esophagogastrostomy (group A) and end-to-side anastomosis (group B), aiming at finding out the mechanism of prevention of anastomotic leakage after "Tunnel" esophagogastrostomy. The results showed that the mucosa of the esophagus and the stomach had fused at the site of the anastomosis on the fifth day in group A and the same processes had completed on the seventh day in group B. The blood supply of "Tunnel" anastomosis is better than that of the conventional end-to-side anastomosis, hence the hastening of the healing process. The protecting barrier formed with the gastric seromuscular in the "Tunnel" anastomosis plays an important role in preventing the occurrence of postoperative anastomostic leakage. PMID- 2096071 TI - Epithelial damage beyond the tip of the endotracheal tube. AB - The effects of ventilator rate and inspired humidity on the large airway epithelium of newborn lambs have been studied using scanning electron microscopy. Significant deciliation, denudation and necrosis occurred at both high and conventional rates if the inspired gas had low humidity. The damage observed was mild in the high humidity groups. PMID- 2096073 TI - Classification schemes of small-for-gestational age and type of intrauterine growth retardation and its implications to early neonatal mortality. AB - Classification of small-for-gestational age (SGA) and pattern of intrauterine growth retardation (IUGR) and their relationship to early neonatal mortality (first 3 days) were studied in a population of 9201 full-term infants in a maternal and child center in Mexico City. SGA infants were classified on the basis of two methods: one, using the tenth percentile of a birth weight (BW) by gestational age reference growth distribution, and the other, using a cut-off point of birth weight of 2900 g. Crown-heel length (CHL) and Rohrer's ponderal index (PI = BW/CHL3) were used to classify patterns of proportionate and disproportionate IUGR. Overall, infants classified as SGA and type of IUGR had an increased risk of death in comparison to full-term appropriate-weight infants. IUGR proportionate infants with short CHL had a significantly greater mortality than disproportionate IUGR infants with normal CHL. A slightly but not significantly greater mortality was observed for IUGR disproportionate versus proportionate using PI regardless of the method of SGA used. The combination of misclassification for SGA and for type of IUGR were examined relative to the availability of gestational age and the uses of data for clinical management versus research. It is concluded that hospitals may tolerate misclassification of SGA but should pay close attention in assessing the pattern of IUGR when evaluating the mortality of newborn term infants. PMID- 2096072 TI - Fetal and neonatal cerebral blood velocity in the normal fetus and neonate: a longitudinal Doppler ultrasound study. AB - In a longitudinal Doppler ultrasound study fetal and early neonatal cerebral blood flow velocities were assessed in the middle cerebral artery in 40 uncomplicated pregnancies during the third trimester of pregnancy and in 22 neonates born from these pregnancies. Peak systolic (PSFV), temporal mean (TMFV), and end diastolic flow velocities (EDFV) were determined and pulsatility index (PI = (PSFV - EDFV)/TMFV) and Pourcelot's resistance index (RI = (PSFV - EDFV)/PSFV) calculated. PSFV, TMFV and EDFV increased during the third trimester of pregnancy and were significantly higher from 36 weeks of gestation onward as compared to values obtained at 28 weeks of gestation, suggesting an increase in actual cerebral blood flow. PI and RI of the MCA did not differ significantly during this period. Immediately after birth PSFV, TMFV and EDFV decreased significantly and remained lower during the first 5 postnatal days compared to fetal values. PI and RI of the MCA tended to decrease during the first postnatal day, but stabilized afterwards. PMID- 2096074 TI - Upper limits of brain blood flow autoregulation in stable infants of various conceptional age. AB - In healthy adults cerebral blood flow is autoregulated and kept constant over a wide range of mean arterial blood pressures (MAP) between 60 and 150 mmHg. In 27 stable infants with different conceptional ages ranging from 33 to 50 weeks, Doppler measurements of mean flow velocity at the anterior cerebral artery have been recorded simultaneously with mean arterial blood pressures (MAP) during a period of 6 h. The range of autoregulation and its upper limit could thus be determined. The upper limit was found to increase with advancing age. In the infants with conceptional ages between 33 and 35 weeks, the upper limit of autoregulation varied between 45 and 60 mmHg, while the upper limit shifted to a MAP of 100 mmHg at 47 weeks conceptional age. A significant positive linear relationship existed between the upper limit of autoregulation and conceptional age. PMID- 2096075 TI - Liver thiol content under varying glucoregulatory states in rats. AB - The influence of varying glucoregulatory states as induced by fasting, feeding and intravenous glucose infusion on liver thiol content has been assessed in the male rat. As expected, increasing the serum glucose levels from 131 +/- 7 mg/dl to 343 +/- 12 mg/dl (mean +/- S.E.) caused a corresponding increase in serum insulin responses. Rising from 3.2 +/- 0.4 mumol/g w.w. in the fasted group to a peak value of 6.3 +/- 0.4 mumol/g (P less than 0.01) in the group infused by 10% glucose solution, hepatic non protein bound sulphydryl groups (NP-SH) were closely related to serum glucose levels up to 244 +/- 11 mg/dl. When higher glucose doses were infused. NP-SH values fell steadily, they even inclined below the level of the fasted rats after infusion of 30% and 40% glucose solutions (1.3 +/- 0.4 mumol/g w.w., P less than 0.05 and 0.7 +/- 0.3, P less than 0.01, resp.), mean serum glucose levels being 291 +/- 12 and 343 +/- 13 mg/dl, resp. Hepatic protein bound thiols were not affected by any of the glucoregulatory states experimentally induced. The data demonstrate that the glucoregulatory state influences hepatic NP-SH content divergently. The study suggests that under physiological conditions liver NP-SH content covariates positively with serum insulin and glucose levels. PMID- 2096076 TI - Effect of varying glucosinolate and iodine intake via rapeseed meal diets on serum thyroid hormone level and total iodine in the thyroid in growing pigs. AB - In a trial with 50 fattening pigs (20 kg initial body weight), the effect of untreated rapeseed meal (RSM) (148 mmol glucosinolates and aglucones per kg dry matter) on the thyroid was compared with RSM treated with Cu2+ (9.5 mmol glucosinolates and aglucones per kg dry matter) and soybean meal (SBM). The diets containing 8% RSM were supplemented with 0.0625-1.0 and the SBM diet (control) with 0.125 mg iodine kg-1 (I). In comparison with SBM fed control, RSM treatment with Cu2+ resulted in a complete normalization of feed intake and growth. Only untreated RSM without I supplementation depressed performance and resulted in symptoms of I deficiency, but the thyroid and liver weight were also increased and the serum T4 content was significantly reduced in animals which were given RSM not supplemented with I, but treated with Cu2+. In young pigs (4 weeks) a plateau of the serum T4 content was achieved from 0.5 mg I kg-1 of the RSM diet onwards. In contrast, when the concentration of goitrogens was reduced by the treatment with Cu2+, the serum T4 level was increased significantly in groups fed with 0.125 mg I kg-1 diet and more. In older pigs (15 weeks) neither the content of goitrogens nor the I dosage affected the serum T4 level. On the other hand, the I content in the thyroid was a good indicator of the different goitrogenicity of the diet in the case of a low I supply. The present investigations show that pig diets with RSM (greater than 10 mmol glucosinolates and aglucones kg-1) should contain at least 0.5 mg I kg-1, but 0.1 mg supplementary I per kg is sufficient in diets without or with a low content (less than 1 mmol glucosinolates and aglucones per kg-1) of antithyroid compounds. PMID- 2096077 TI - Nuclear binding of thyroid hormones and activity of malic enzyme and ornithine decarboxylase in rat liver during postnatal development. AB - The binding of 3,5,3'-L-triiodothyronine (T3) and thyroxine (T4) on liver nuclear receptors and the activity of malic enzyme and ornithine decarboxylase was examined in infantile rats aged in 1, 3, 7, 23, 29 days and in adult rats. No changes in the affinity constants (Ka) of nuclear receptors were observed for T3 or T4. The maximum binding capacity (MBC) estimated with the use of Scatchard plot analysis was unchanged for T3, the highest MBC for 125I-T4 being noted in rats aged 7 days. Malic enzyme activity in rat liver during the first three neonatal weeks was almost undetectable, but markedly increased on the 29th day. Ornithine decarboxylase activity was found to be significantly higher on the first day after birth as compared with that of the remaining age groups. The findings indicate that the thyroid hormone-nuclear receptor complex in rat liver does not seem to be sufficient for the induction of these enzymes in postnatal period of life. PMID- 2096078 TI - Nonsteroid antiandrogen inhibiting effect on testosterone metabolism in rat prostate and liver. AB - The effect of nonsteroid antiandrogen flutamide on 3H-testosterone (3H-T) metabolism in vitro was studied in Wistar male rat prostatic and hepatic homogenates. Flutamide was administered per os in a dose of 25 mg/kg daily for 3, 10 or 30 consecutive days. Following 30 days 5 alpha-dihydrotestosterone (DHT) formation in the prostate was reduced by 50%. In castrated animals antiandrogen abolished the recovering action of testosterone propionate (TP) on 5 alpha reductase activity. When added to incubation medium flutamide proved ineffective, while hydroxyflutamide appeared to decrease DHT formation. The metabolic utilization of 3H-T in the liver of rats receiving flutamide for 30 days was found to be 3 times lower. The formation of DHT, androsterone, ethiocholanolone and androstenedione was substantially suppressed. In castrated rats, both treated and nontreated with TP, flutamide also inhibited the formation of steroid metabolites of 3H-T. Synergism to flutamide and TP action on androgen metabolism in the liver is suggested to be related to antiandrogen ability of interaction with an unusual estrogen-binding protein of rat liver. The decrease in DHT formation induced by flutamide may play a role in the mechanism of its therapeutic action in prostatic cancer patients. PMID- 2096079 TI - The influence of PRL, LH alone and in combination upon progesterone secretion by porcine luteal cells in aggregate culture. AB - Corpora lutea removed from ovarian of cycling pigs in early luteal phase (1-3 days) were used. After enzyme dispersion the luteal cells were suspended in medium M 199 supplemented with 10% of calf serum. Cultures were carried out in triplicate and incubated at 37 degrees C for 24 h. After that time the following hormones were added to the culture medium; 100 ng LH, or 100 ng PRL or 100 ng LH plus 100 ng PRL. The cells were incubated with hormone for 6, 12, 24 and 48 h. LH added to the medium resulted in the increase of progesterone secretion (P less than 0.05) only during 6 h incubation (140% of control progesterone). Stimulatory effect of PRL was observed only after 12 h incubation (300% of control progesterone; P less than 0.001). The addition of LH plus PRL decreased progesterone secretion after 6 h incubation (33.3% of control progesterone; P less than 0.05), a little stimulatory effect being observed after 24 h incubation (141% of control progesterone). This study confirmed the results obtained with monolayer cultures previously described. PRL appeared to be a luteotrophic hormone which is responsible for the increase of progesterone secretion by the early developing corpus luteum of pig. From these data it was concluded that luteal cells may require either LH or prolactin but not both at a time to sustain higher level of progesterone secretion. PMID- 2096080 TI - Cell-mediated immunity: role of IL-3 and IL-6 in the regulation of contact sensitivity reaction. AB - Delayed type hypersensitivity reaction (DTH) consists of a sequential cascade of steps depending on different types of T cells, as well as mast cells, endothelial cells and macrophages. Recently it has been shown that CD4+ TH1 lymphocytes ("inflammatory type") play a central role in DTH reaction. Activated TH1 cells produce a characteristic pattern of cytokines: IL-2, IL-3, TNF-beta, IFN-gamma. Using the contact sensitivity (CS) reaction on mice as a model system, the role of cytokines in the regulation of DTH is presented, particularly the significance of IL-3 and IL-6. The recent data can be interpreted to show that IL-6 released by activated macrophages (APC cells) in the induction phase of the CS reaction probably stimulate CD8+ T suppressor cells. These in turn inhibit the production of IL-2 and IL-3 by CD4+ TH1 cells followed by a state of unresponsiveness. PMID- 2096082 TI - Expression of GFAP (glial fibrillary acidic protein) antigenicity and differentiation of glioma tumor cells of astrocytic origin. AB - Polyclonal antibodies were used in the diagnostic procedure of brain tumors of astrocytic origin. Investigations were undertaken to determine the percentage of GFAP positive and negative cells in arbitrary selected fields of the tumor specimen taking into account the number of mitotic figures and the diameter of the cell nucleus. It has been found that 18.0% cells were GFAP positive in fields with mitotic figures and in 29.8% cells in fields without mitoses. If the differences in nucleus diameter are concerned the GFAP positive cells constituted 64.2% of cells with diameter between 6 to 10 microns. Instead 78% of GFAP negative cells had a diameter of 6.4 to 7.2 microns. The results indicate that cells with a smaller diameter of the nucleus and localized in fields with mitotic figures are considerably less frequently GFAP positive as compared with cells of larger diameter of the nucleus and localized outside the fields with mitoses. It is suggested that cells of higher differentiation show an undisturbed organization of the cytoskeleton as compared with their counterparts. Thus the determination of GFAP antigenicity can be considered as a tool in the evaluation of differentiation of the tumor and as an indicator of its heterogeneity. PMID- 2096081 TI - Indoxyl alfa-D-galactoside as the temporarily last substrate for glycosidase histochemistry. The present state of the art in histochemical glycosidase research using indoxyl glycosidas. AB - Initiated by the recently published histochemical method for the investigation of alfa-D-galactosidas with an indoxyl substrate, the current state of this group of synthetic compounds in light and electron microscopic histochemical glycosidase research is evaluated whereby historical, functional, methodological and applied aspects are considered. Beginning with the introduction of indoxyl acetate for non-specific esterase in 1951 and 1952 numerous other indoxyl substrates and mostly substituted in the 5- and 4-position of the indol ring by Br and Cl were developed to study histochemically non-specific phosphatases and glycosidases and frequently used in indigogenic, azoidoxyl, tetrazolium salts and metal salt techniques for catalytic (activity) histochemical and less often for immunohistochemical, affinity histochemical and hybridohistochemical purposes. The last substrate which became available and was validated for activity histochemistry was 5-Br-4-Cl-3-indoxyl alfa-1-galactoside for alfa-1 galactosidase. At present, the indoxyl glycosides are more widely used than 5-Br 4-Cl-3-indoxyl acetates and phosphates when compared with the alternative synthetic (artificial) naphthol, 6-Br-2-naphthol or ternative synthetic (artificial) naphthol, 6-Br-2-naphthol AS substrates, and among the indoxyl glycosides those for the oxoglycosidases lactase, maltase-glucoamylase, glucoamylase, acid beta-D-galactosidase, neuroaminidase and alfa-D-galactosidase are superior to other artificial compounds. When one considers in addition, electron microscopic catalytic glicosidase histochemistry (ultracytochemistry, 5 Br-4-Cl-3-indoxyl is the only suitable moiety for this purpose. These glycosidase can mostly be localized in plasma membranes or lysosomes and also measured there in tissue sections but are also found in secretion granules, endoplasmic reticulum and organ lumina. PMID- 2096084 TI - [Effects of surface-active substances with antistatic properties on several immunity indices]. AB - In experiments performed on rats, it was established that the antibodies' formation was stimulated as a result of a combination of staphylococcal anatoxin or E. coli vaccine immunization with the administration of the non-ionogenic surface-active substances (SAS) Stearox-920 and OC-20. Those SAS proved to have immunostimulating properties, and Stearox-920 was more effective. Another experimental study revealed a growing bactericide activity of the skin, which could be seen from the rate of its self-cleaning from the standard E. coli suspension. PMID- 2096086 TI - [A comparative hygienic evaluation of new forms of labor organization in the Kuzbass coal mines]. AB - It was established that transition to the contract forms of organization of labour in mines, in spite of higher moral incentives for miners and improved psychological climate in work teams, led to increased influence of industrial factors, physical and neuro-psychic overload, which potentially is fraught with health state degradation. In case with new forms of organization of labour, preventive measures should be directed towards the improvement of hazardous labour conditions, norms of workload and stimulation of rehabilitation activities. PMID- 2096085 TI - [Occupational health in the manufacturing of lithium, niobium and tantalum-based monocrystals]. AB - The article contains a complex hygienic assessment of the technological processes, labour conditions and equipment in processing and use of lithium, niobium and tantalum based monocrystals. Major hazardous factors were established with a set of preventive measures elaborated. PMID- 2096083 TI - [Combined effects of formaldehyde and increased barometric pressure in animals]. AB - A study was performed on white rats of the physiological, biochemical, haematological and pathomorphological indices in separate and combined actions of formaldehyde (FA) (60.0 +/- 12.7 mg/m3 in one-time exposition and 7.2 +/- 1.2 mg/m3 in a 30-day long experiment) with a concomitant increased barometric pressure (IBP) characteristic of deep coal mines (111 and 123 kPa corresponding to 1000 and 2000 m deep mines respectively). It was established that, at 123 kPa, lipoid peroxide oxidation process was stimulated in combination with microcirculatory disorders, growing FA concentration in the serum and pulmanary tissues. The shifts were still more vivid at growing IBP. PMID- 2096087 TI - [Labor conditions and health status of the workers engaged in the production of inorganic salts of manganese]. AB - It was established that the major hazardous factor in nitrate, sulphate and manganese basic carbonate processing shops was the dust of the final product. Upper respiratory tract (catarrhal, subatrophic rhinitis, pharyngitis, laryngitis), skin (allergic and contact dermatitis) and cardiac disorders were specified as the predominant pathology among manganese compounds processing shop workers. Mineral exchange disorders, lowered glucose content in the blood and violation in the acid persistence of the erythrocytes were revealed through medical examinations. PMID- 2096088 TI - [Morpho-functional state of the spermatogenic epithelium in rats under chronic inhalation effects of dispersible 2K orange azo dye]. AB - The article contains a morphofunctional evaluation of spermatogenic epithelium state in rats after chronic inhalation of Orange-25 disperse azo dye. The result of the study revealed gonadotoxic effects at both concentration levels 28.5 mg/m3 and 5.6 mg/m3, which manifested themselves through violations in the spermatozoa functional states and changes in the seminiferous epithelium morphometric indices. Judging from the affection of the blood, the concentration 28.5 mg/m3 can be considered toxic, and 5.6 mg/m3 can be regarded liminal. Thus, the gonadotoxic effect was a secondary one, as in male rats in both groups, a hemotoxic effect was revealed at toxic and liminal dosage concentrations. PMID- 2096089 TI - [Physiological-hygienic assessment of traditional and new ways of work organization at raw materials shops in meat processing industries]. PMID- 2096090 TI - [Physiological-hygienic aspects of the work of tractor drivers engaged in open soil vegetable planting]. AB - The labour conditions of tractor drivers engaged in open soil vegetable planting in subtropical zones were characterized by the unfavourable influence of weather, noise and vibration, dust and exhaust contamination, and by static tension. The physiological studies performed revealed considerable tensions of the CVS, CNS, thermoregulatory and muscle systems in the drivers. The specificity of the identified changes confirmed marked decrease in the functional resources of the organism, which should be taken into account when providing medical services to the drivers. PMID- 2096091 TI - [Morphology of experimental extrinsic allergic alveolitis caused by dust typical to swine-breeding farms]. AB - Prolonged experiments performed on white rats revealed that inhalation of the dusts of swine-breeding farms caused the development of exogenous allergic alveolitis with the clinical picture of its acute and preacute stages. The characteristics of the immuno-morphologic changes fully depended on the dust concentration levels and the duration of the contact. PMID- 2096092 TI - [Gas chromatography methods of the measurement of concentrations of 2-bromo-6 chloro-4-nitroaniline, N,N-dioxyethyl-M-chloroaniline, N-oxyethyl-N-beta cyanoethylaniline and N-ethyl-N-beta-cyanoethyl-M-toluidine in the working zone air]. PMID- 2096093 TI - [Use of thin-layer chromatography in the measurement of concentrations of red brown G, grey C and bright pink C vat dyes in the work zone air]. PMID- 2096094 TI - [Determination of dimethyl cadmium in the air]. PMID- 2096095 TI - [Laser therapy in dust bronchitis]. AB - Laser therapies of 43 dust bronchitis patients (4 cases in 1st stage and 39 cases in 2nd stage) were performed in comparison with routine therapeutic procedures of 28 patients (6 cases in 1st stage and 22 cases in 2nd stage). 14 acupuncture points were selected. A good therapeutic effect was attained in 16.3% sample group and 7.1% control group patients, satisfactory results--in respectively 58% and 42.9% cases, insignificant results--in 25.6% and 50% cases. Along with the favourable therapeutic effect, a positive influence of laser therapy on the immune system was established, particularly on the immunity T-system, in dust bronchitis cases. Laser therapy was recommended as part of complex treatment procedures for dust bronchitis patients. PMID- 2096096 TI - [A system of measuring physiological characteristics of the state of laboratory animals by rapid analysis]. PMID- 2096098 TI - [Experimental data on elaboration of a diet in conditions affected by phenol and formaldehyde]. PMID- 2096097 TI - [Hygienic assessment of the contents of hazardous substances in plywood glue shop]. PMID- 2096099 TI - Vitamin E activity of 1-thio-alpha-tocopherol as measured by the rat curative myopathy bioassay. AB - The bioactivity of the acetate of the all-racemic, 1-thio analog of alpha tocopherol (all-rac-1-thio-alpha-tocopheryl acetate) has been determined by measuring its ability to decrease plasma levels of pyruvate kinase in vitamin E deficient rats using the curative myopathy bioassay. The thio analog is only 0.22 times as active as RRR-alpha-tocopheryl acetate and is therefore approximately 0.33 times as active as all-rac-alpha-tocopheryl acetate, since the latter has been shown to be 1.47 times less active than RRR-alpha-tocopheryl acetate in the same bioassay (H. Weiser, M. Vecchi and M. Schlachter, Internat. J. Vit. Nutr. Res., 55, 149-158 (1985)). The 0.33:1.0 ratio is similar to the ratio of 0.41:1.0 measured for the in vitro antioxidant activities of the corresponding free phenols. This finding lends further support to our view that the vitamin E activity in the curative myopathy bioassay of close structural analogs of alpha tocopherol is determined primarily by the in vitro antioxidant activity of the analog relative to alpha-tocopherol, consistent with the belief that vitamin E functions primarily as a general purpose, lipid-soluble antioxidant in mammals. PMID- 2096100 TI - Redox buffering ability of lymphoid cells evaluated by the oxidation of 2',7' dichlorofluorescin. AB - The redox buffering activity of several lymphoid cells against endogenous and exogenous H2O2 has been evaluated using 2',7'-dichlorofluorescin diacetate (DCFH2 DA). The mechanism of 2',7'-dichlorofluorescin (DCFH2) oxidation has also been investigated. It was found that while the oxidation by external H2O2 is completely inhibited by azide or cyanide, the oxidation by endogenous species is still present, even under anaerobic conditions. The data herein reported indicate that autoxidation and peroxidation of DCFH2 are distinct reactions. Hence only by addition of increasing concentrations of exogenous hydrogen peroxide, the fluorescence of DCF can be used to evaluate the cellular ability of scavenging H2O2. By this method we have found that the erythroleukaemia cell line K562 and promyelocytic line HL-60 show a faster rate of DCFH2 oxidation than peripheral blood leukocytes (PBL), mature T-cells (MOLT-3 and MOLT-4) and B-cells (DAUDI). Using this method the balance between antioxidant enzymes activity and the redox state of the cell can be easily assessed by fluorescence both in single cells and in cell populations. PMID- 2096101 TI - Normolipidaemic activity of liposomal-encapsulated superoxide dismutase in rats. AB - To determine the regulatory effects of superoxide dismutase (SOD) on lipid metabolism a simple model of hyperlipidaemia induced by a hypercholesterolaemic (HCT) diet in rat was used. In animals fed a HCT diet, triglyceride (TG) were increased by 126%, total cholesterol (TCT) by 40%, very low density lipoprotein (VLDL) by 124% and the TCT/HDL ratio by 82%. The procedure would therefore appear to model some of the risk factors of atherogenesis. In animals fed a hypercholesterolemic diet, liposomal Cu-SOD (200 micrograms/kg i.m. every two days; 1000 micrograms/kg i.m./day) decreased TG by 29 and 49%, TCT by 14 and 36%, TCT/HDL ratio by 32 and 60%, VLDL by 52 and 55% respectively and increased high density lipoprotein cholesterol (HDL-C) by 17 and 46% respectively. The present experiments show therefore that the administration of liposomal SOD has a marked effect on lipid parameters (particularly TCT and TG) and might therefore reduce the atherogenic risk by increasing HDL and decreasing VLDL and cholesterol atherogenicity ratio (CAR). PMID- 2096103 TI - Pharmacological aspects of chiral nonsteroidal anti-inflammatory drugs. AB - Most NSAIDs are chiral molecules: they exist under 2 configurations of non superimposable mirror images which are termed enantiomers or optical isomers or optical antipodes. Direct or indirect (resolution) methods are used to separate this equal mixture of compounds. Some of the enantiomers of the NSAIDs are able to undergo chiral inversion from the inactive R(-) to the active S(+) form. The pharmacokinetics in terms of absorption, distribution, metabolism, protein binding and elimination may be different for the 2 enantiomers, leading to interindividual variability in clinical response and drug toxicity. PMID- 2096102 TI - Effects of CCl4 poisoning on metabolism of dolichol in rat liver microsomes and Golgi apparatus. AB - Carbon tetrachloride (CCl4) poisoning affects glycoprotein processing and maturation at the level of rat liver microsomes and Golgi apparatus. HPLC analysis showed that within 5-60 min after CCl4 administration the levels of total dolichol, free dolichol and dolichyl-phosphate strongly decreased both in total microsomes and in Golgi apparatus. The most marked and early reduction of total dolichol was observed in the secretory membranes of Golgi area already 15 min after CCl4 poisoning. The incubation of CCl4-pretreated isolated hepatocytes with [3H]-mevalonate showed a significant slowing down of the label incorporation into both free-dolichol and dolichyl-phosphate. Moreover, lipid peroxidation might cause alterations in the molecular structure of both free-dolichol and dolichyl-phosphate. A notable prevention of dolichol decrease was observed in animals pretreated with vitamin E. The results suggest that the prooxidant activity of CCl4 is able to affect the metabolism of dolichol either by increasing the oxidative degradation or impairing the biosynthetic pathway. PMID- 2096104 TI - Pharmacokinetics of flunitrazepam following single dose oral administration in liver disease patients compared with healthy volunteers. AB - The pharmacokinetic behaviour of flunitrazepam and its main active metabolite, N desmethyl flunitrazepam, was investigated in 12 patients with liver disease (cirrhosis or hepatitis) compared to 6 healthy volunteers. A gas-liquid chromatographic method allowing for simultaneous determination of flunitrazepam and N-desmethyl flunitrazepam in plasma samples was developed. The accuracy and the precision near the quantification limit of ca. 1 ng/ml were better than 5%. Plasma levels of flunitrazepam were not significantly altered by hepatic failure, whereas plasma levels of N-desmethyl flunitrazepam were lower in patients than in healthy subjects. Pharmacokinetic parameters did not differ significantly between healthy subjects and liver disease patients: the oral clearance was 3.5 +/- 0.8, 3.5 +/- 1.9 and 4.0 +/- 1.2 ml/min/kg, respectively in healthy subjects, patients with hepatitis and patients with cirrhosis. The apparent elimination half-life was 22 +/- 5 h in healthy subjects, 25 +/- 10 h in patients with hepatitis and 20 +/- 6 h in patients with cirrhosis. However, the expected increase of the drug free fraction during liver disease could decrease the therapeutic and toxic ranges of flunitrazepam in these patients. PMID- 2096105 TI - Tianeptine and its main metabolite. Disposition in chronic renal failure and haemodialysis. AB - The disposition of the antidepressant tianeptine and its MC5 metabolite (pentanoic acid analogue of tianeptine) was studied following a single 12.5 mg oral dose of tianeptine sodium salt in 20 patients with chronic renal failure. In 12 patients (group I) having a creatinine clearance of less than 19 ml.min-1 the pharmacokinetics parameters for tianeptine and MC5 metabolite were determined and compared with those obtained in a matched control group (group II). The other 8 patients (group III) were functionally anephric and were studied during 1 dialysis to assess the haemodialysis clearances of tianeptine and MC5 metabolite. The comparison between groups I and II showed that renal failure did not appear to affect the disposition of parent tianeptine. However, the MC5 metabolite terminal half-life was found to be increased in renal patients compared to controls (14.2 +/- 9.3 h vs 4.9 +/- 1.7 h). Due to a large interindividual variability the difference did not reach a significant level (P = 0.054). According to the antidepressant activity of the MC5 metabolite in pharmacological tests, the sustained rise in its plasma level suggests that a reduced daily dose should be administered and 12.5 mg of tianeptine should be given twice daily to patients with chronic renal failure. In patients from group III elimination of the compounds by haemodialysis was found to be low. The dialysis clearances were 3.9 +/- 9.9 ml.min-1 and 19.2 +/- 8.6 ml.min-1 for tianeptine and its MC5 metabolite respectively. This low dialysability has 2 clinical implications. Firstly, patients currently undergoing haemodialysis and treated by tianeptine could be given the drug without taking dialysis into account. Secondly, haemodialysis does not appear to be an effective method for tianeptine elimination in cases of overdosage. PMID- 2096106 TI - Effect-kinetic characterization of dimethindene maleate following oral administration (Fenistil, Tropfen). AB - Dimethindene maleate is a well known H1-receptor antagonist with strong affinity to the H1-receptor. In order to evaluate the time course of its activity, dimethindene maleate was investigated in a histamine provocation model in man. Eight healthy male volunteers were treated either with 4 mg dimethindene maleate using a commercially available solution (Fenistile, Tropfen) or an identically appearing placebo solution (po) following a double-blind, crossover study design. Intracutaneous histamine injections were administered at -1, 2, 5, 14, 17, 20, 23, 26 and 29 h following drug administration. Areas of flares and weals were measured 5, 10, 20, and 30 min following histamine provocation. A strong inhibition of the development of flares and weals was observed to be more pronounced in flares than in weals. Baseline adjusted areas under the curve differ statistically significantly following verum and placebo treatment conditions (P = 0.0028). According to the time schedule of the study maximal effects were observed at time point 5 h. The mean residence times of the inhibitory effects were calculated to be congruent to 13 h compared to the mean residence times of dimethindene blood levels of approximately 8 h indicating a non-linear relationship between blood level and effect. PMID- 2096107 TI - Influence of diuretics on brachial artery diameter and distensibility in hypertensive patients. AB - Blood pressure, brachial artery diameter and pulse wave velocity were determined before and after diuretic treatment in 2 groups of hypertensive patients treated either by indapamide (2.5 mg per d) or by canreonate (50 mg per d). Brachial artery diameter, measured from pulsed Doppler flowmetry, and pulse wave velocity, evaluated from mechanography, did not alter significantly despite a significant blood pressure reduction. The study indicates that, in hypertensive patients of middle age, diuretics did not change brachial artery diameter and distensibility, whether the drug caused an increase or a decrease in plasma potassium levels. PMID- 2096109 TI - [Data transfer between articulator and cephalograms for preparation of diagnostic set up and visual treatment objective in complex treatment case]. PMID- 2096108 TI - Randomized double-blind trial of injectable heptaminol for controlling spontaneous or bromocriptine-induced orthostatic hypotension in parkinsonians. AB - Heptaminol is a molecule with experimental cardiovascular analeptic properties. In this double-blind vs placebo trial, the potency, so far unproven, of the injectable form of a 626 mg dose of heptaminol chlorhydrate on spontaneous or induced orthostatic hypotension (OH), was assessed. Nineteen patients were included in the study: 7 displayed spontaneous OH, and in the other 12 OH was induced by bromocriptine, as monitored 103 min/after an oral intake of 6.6 mg on average. Neither spontaneous nor induced OH were recorded in 32% of the Parkinsonian population registered, with no obvious distinctive characteristics. Potency tilt-trials, performed 15, 30 and 45 min after parenteral administration of heptaminol, revealed a significant and expressive potency of the molecule on the systolic blood pressure after 15 min (P less than 0.05). Clinical and biological tolerance was excellent. Low plasma renin activity and the absence of response to orthostatism indicated, in this population of Parkinsonian extrapyramidal syndromes, a loss in positive tonus likely to be of sympathetic origin. The anti-hypotensive action of heptaminol does not seem to be related to any renal or even sympathetic interaction. PMID- 2096110 TI - Does vasectomy have long-term effects on somatic and psychological health status? AB - All the major international articles on the somatic and psychological consequences of vasectomy published over the last 10 years have been reviewed and analysed. Although some experiments on animals have revealed harmful effects, none of the large-scale epidemiological studies has pointed to any increase in health risks (cardiovascular, hypertensive, psychiatric) in vasectomized men. The contradictions which arise between the clinical and large-scale epidemiological studies may be the result of methodological or experimental conditions. As our knowledge stands at present it can therefore be considered that vasectomy has no major effects on the physical or mental health of men. PMID- 2096111 TI - Immunohistochemical localization of inhibin-alpha in the testes of normal men and in men with testicular disorders. AB - Testicular biopsies from normal men and from men with testicular disorders were examined by immunohistochemistry for the presence of the inhibin-alpha subunit using two different antisera. Immunoreactive inhibin-alpha (irI-alpha) was found in Leydig cells in normal, oligospermic, and azoospermic men and in men with Klinefelter's syndrome, and it was also found in a Leydig cell tumour. hCG treatment apparently increased the amount of immunoreactive inhibin-alpha, particularly in Leydig cells. Sertoli cells also contained irI-alpha but the staining intensity was considerably stronger in testes with impaired spermatogenesis or Sertoli-cell-only syndrome than in normal testes. It is suggested that the serum concentration of irI-alpha and inhibin in humans may, in a complex way, be related to both Leydig and Sertoli cell function, and that the relative contribution from these cells may change in cases of testicular malfunction. PMID- 2096112 TI - Distribution pattern of testicular sulphydryloxidase immuno-activity in the djungarian hamster (Phodopus sungorus) during photoperiodically induced involution and recrudescence. AB - The distribution pattern of testicular sulphydryloxidase (SOx) immuno-activity was investigated in the djungarian hamster during photoperiodically induced testicular involution and recrudescence. SOx immuno-activity, indicating functional integrity of labelled cells, did not change in pachytene spermatocytes and spermatids as long as these cells were present in the seminiferous epithelium. Its disappearance coincided with the degeneration of spermatocytes in phases IV and V of involution and reappeared during recrudescence, when the first spermatogenic wave had reached the pachytene stage. In tubules at phase VI of involution (showing maximal regression), the apical cytoplasm of Sertoli cells showed immuno-activity. This immuno-activity disappeared during recrudescence prior to the differentiation of pachytene spermatocytes. Changes in SOx immuno activity resembled those of lactate dehydrogenase-X (LDH-X) in photo-inhibited testes or during puberty, indicating a close functional relationship which still remains to be elucidated. The data suggest that the hamster exposed to different photoperiods can be used as a suitable model to study the relationship between testicular morphology and function in different states of gonadal activity. PMID- 2096113 TI - Are eosinophil leucocytes involved in the oestrogenic response of the postnatal rat epididymis? AB - The effects of oestrogens and androgens, alone or in combination, on several epididymal parameters have been studied in 15-day-old rats after neonatal treatment. Oestrogens induced several responses, such as increased growth of the fibromuscular stroma and eosinophil leucocyte accumulation, whereas the proliferative activity of the epithelium was decreased significantly. Otherwise, the density of intra-epithelial leucocytes was not modified. Different oestrogen induced responses, such as the increase in volume of the fibromuscular stroma and eosinophil leucocyte accumulation were inhibited by treatment with testosterone, whereas dihydrotestosterone had no appreciable effect. This study raises the possibility that eosinophils are mediators of some of the oestrogenic responses in the early postnatal rat epididymis. PMID- 2096114 TI - Studies of pyrimidine metabolism during chick development: two enzymes involved in UMP breakdown. AB - The pattern of uridylate phosphatase and uridine phosphorylase has been studied in the liver, brain, heart and thigh muscles of the chick during development. The study of enzymes involved in pyrimidine metabolism confirms that differences in utilisation of the metabolic pathways exist during ontogenesis. In the liver, starting from the 12th day, an active metabolic pathway, leading to UMP via cytosine should be added to the catabolic ones. In the brain, the second period of embryogenesis should be characterized by a lower utilisation of the catabolic pathways and by an increase of the anabolic ones. In the heart, pyrimidine metabolism during development regards especially UMP. In skeletal muscle, pyrimidine metabolism shows low activity. PMID- 2096115 TI - Fucose-carrying nuclear glycoproteins: distribution and tissue specificity. AB - Glycoproteins recognized by Ulex europaeus lectin I, specific for fucose residues, have been identified in chromatin prepared from pig liver, heart and kidney nuclei. They are present among the proteins dissociated from DNA with salt solutions and, in higher amount, among the proteins dissociated with urea and guanidine. In any case these fucose-containing glycoproteins appear to have a marked tissue specificity, which suggests that they have specific regulatory roles in the processes taking place in the nuclei. PMID- 2096116 TI - Stressors, coping mechanisms, and perceived health in persons with epilepsy. AB - Knowledge is lacking about the nature of stressors experienced by persons with epilepsy and the strategies used to cope with these stressors. This study explored epilepsy-specific stressors, coping strategies used, level of trait anxiety, and perception of health in 107 adults who had had epilepsy for 1 year or longer. 'Need to take medications regularly' and 'Uncertainty about when a seizure will occur' were the stressors subjects ranked highest. 'Try to maintain some control over the situation', 'Hope things will get better', and 'Think through different ways to solve the problem' were the top coping strategies used. Persons who perceived their health as better used more problem-oriented strategies than did those who rated their health as poor. The mean level of trait anxiety was 42.1, which is higher than that for a normal population. Continued studies are needed to more clearly identify stressors experienced at various times in the trajectory of epilepsy and the precise coping strategies used for specific stressors. PMID- 2096117 TI - The effects of physical exercise training and cardiac education on levels of anxiety and depression in the rehabilitation of coronary artery bypass graft patients. AB - OBJECTIVE: to evaluate whether an exercise and education-based rehabilitation programme is sufficient treatment for individuals with clinically significant levels of anxiety or depression following coronary artery bypass graft (CABG) surgery. DESIGN: follow-up and repeated assessment after surgery. SETTING: outpatient cardiac rehabilitation programme. PATIENTS: all 88 attenders after CABG surgery. ASSESSMENTS: structured interview and Hospital Anxiety and Depression (HAD) scale (using 8 as the cut-off) administered by rehabilitation nurses at start of course and HAD repeated at 12 weeks and 6 and 12 months (by post after discharge). RESULTS: return rates of 76 and 80% at 6- and 12-month assessments, respectively; statistically significant reductions in levels of anxiety and depression found between first and all subsequent assessments; subdividing into groups revealed significant reduction in anxiety and depression in the anxious and depressed groups at 12 weeks and 6 months, respectively, but at 12 months there was no significant reduction. CONCLUSIONS: there is a need to address the problems of anxiety and depression directly by screening and treatment, and to provide more psychologically-orientated cardiac rehabilitation programmes. PMID- 2096118 TI - Clinical, social, and psychological factors and outcome in a 5-year follow-up study of 276 patients hospitalized because of suspected lumbar disc herniation. AB - The study consisted of 276 patients who were hospitalized between 1980 and 1982 because of suspected lumbar disc herniation. No randomization of treatment was used. On the basis of clinical indications 179 patients were operated on and 97 had further conservative treatment. Results of physical, social, and psychological examinations performed after 1 year were related to the 5-year outcome defined by occupation handicap of the WHO system. For operated patients, subjective working incapacity, sensory deficit of leg, tightness of hamstrings, age, and pain in lumbar extension predicted a poor outcome. Predictive factors for non-operated patients were increased occurrence of occupational hazards and co-morbidity. PMID- 2096119 TI - Outcome following physical trauma: a comparative approach. AB - This study aimed to examine physical and psychosocial changes after injury in a range of trauma patients. Three groups were selected for comparison purposes: severely head-injured patients, patients with major trauma, and those with minor trauma (n = 102). Outcomes were assessed by questionnaires and inventories administered to a family member or friend of the trauma survivor, approximately 1 year post-injury. Severely head-injured patients were reported to have the greatest degree of difficulty in self-care and mobility, and in community living skills, followed by other major trauma patients and then minor trauma patients. Severely head-injured patients also had relatively more frequent reports of behavioural changes than the other two groups. None the less, more than half of the major trauma group were reported to act differently after the accident. The relative frequency of adverse outcomes in the major trauma group was greater than expected and should be the focus of further research. PMID- 2096120 TI - Gait recovery after hemiplegic stroke. AB - We prospectively evaluated gait recovery in 197 elderly subjects after hemiplegic stroke by measuring serial walking speed. Fifty-seven per cent of subjects (113/197) could not walk without human assistance on day 7 post-stroke. About 40% of this group achieved gait independence at months 1, 2, 3, and 4 post-stroke. In contrast, about 95% of those walking on day 7 maintained gait independence 1, 2, 3, and 4 months post-stroke. Using multiple logistic regression, the best predictors of independent ambulation among the 113 subjects not walking on day 7 were age, line bisection error, and leg power. PMID- 2096121 TI - A short screening test for visual neglect in stroke patients. AB - OBJECTIVE: to extend a preliminary study of the internal structure of six measures comprising the 'conventional' subtests of the Behavioural Inattention Test (BIT) in order to develop a short screening test for visual neglect. DESIGN: discriminant function analysis of the 15 tests constituting BIT. SETTING: rehabilitation centre. PATIENTS: 59 selected from consecutive stroke patients entering the centre. SELECTION CRITERIA: absent prior history of major CNS disorder, at least 1 week post-stroke, right-handed for writing, absent significant visual impairment other than visual field deficit, no psychiatric overlay or generalized intellectual deterioration, and ability to comprehend and respond to the visuomotor tasks administered. COMPARISON GROUP: 50 non-brain damaged subjects (hospital employees, members of University subject panel, and local community volunteers). ASSESSMENTS: the 15 tests constituting the BIT. RESULTS: two subtests, letter cancellation and star cancellation, were the most sensitive measure, identifying 74% of neglect patients with no false positives. CONCLUSIONS: letter and star cancellation offer an adequate yet brief screening test for determining which patients might benefit from administration of the complete neglect test battery. PMID- 2096122 TI - Cytotoxic therapy. Role of durable venous access. AB - Aggressive chemotherapy regimens and supportive measures in haemato-oncology patients demand reliable venous access. Experience with this method in India has been limited. During a period of six months, we have used 42 subclavian indwelling catheters and 31 cubital Cavafix long lines. The mean age of patients in the two groups was 32 years and 7 years respectively. Subclavian catheters had a median duration of catheter placement of 46 days (range 4-145) and total 1494 catheter days, while cubital longlines yielded a median duration of insertion of 14 days (range 4-27) and total 508 catheter days. Catheter related complications were infection in 25% of patients, thrombophlebitis in 22%, blockade in 12% and misplacement in 17% in both groups taken together. The patients and families were extremely satisfied with the devices. Our experience supports further use of durable venous access in cancer patients. Implanted central venous catheters should be preferred whenever feasible. PMID- 2096123 TI - Chronic granulocytic leukaemia. A study of 160 cases. AB - Chronic granulocytic leukaemia (CGL) is the commonest leukaemia among adults in India. Case records of 183 CGL patients diagnosed between 1975 and 1985 were reviewed. The median age at diagnosis was 40.5 years. Most patients presented with weakness, fullness in the left upper abdomen and fever. Splenomegaly and hepatomegaly were present in 90% and 48% respectively. Patients were treated with oral, intermittent busulphan with monitoring of total leucocyte count. Overall, 87 patients expired, including 63 (72%) due to blast crisis. The median survival was 33 months from diagnosis and 44 months from the onset of symptoms. PMID- 2096124 TI - Pregnancy with heart disease. Experience at Postgraduate Institute of Medical Education and Research, Chandigarh. AB - Pregnant patients with heart disease seen between 1980 and 1985 were studied. The incidence of heart disease in pregnancy was 1.3%. Rheumatic heart disease was the commonest lesion (78%), followed by congenital heart disease (18.7%). In the rheumatic heart disease group, mitral stenosis was the commonest lesion (71.54%), and patients who had been or were operated on for their heart disease had less severe dyspnoea and fewer complications. The mode of delivery and the foetal and maternal mortality did not differ significantly in operated and non operated patients. PMID- 2096125 TI - Complications of intermittent peritoneal dialysis. AB - Two hundred and ninety three sessions of intermittent peritoneal dialysis were carried in 158 cases of renal failure between 1984 and 1987. The complications encountered during the procedure were grouped as mechanical in 29 (17.9%), circulatory in 26 (15%), neurologic in 21 (13.4%) and biochemical in 54 (34.1%) cases. Unexplained respiratory arrest with spontaneous recovery occurred in 2, infections in 5 and miscellaneous complications in 19 (12%) cases. Bradycardia and cardiac standstill were observed in one patient. Most of the complications were managed uneventfully. There was no mortality. PMID- 2096126 TI - Renal papillary necrosis in diabetes mellitus. AB - Renal papillary necrosis in 4 diabetic patients is described. Two of them had underlying diabetic nephropathy. Urinary tract infection was present in all of them. Three patients had passed fleshy material in the urine while in one the diagnosis was established by excretory urography. Two patients required haemodialysis for acute renal failure caused by sloughed papillae. The condition should be suspected in diabetic subjects who develop recurrent episodes of urinary tract infection, renal colic, haematuria or obstructive uropathy. PMID- 2096127 TI - Effects of commonly used NSAID's on gastric mucosa. A clinico-endoscopic and histopathological study. AB - Non steroidal anti-inflammatory drugs (NSAID's) are one of the most commonly used agents in clinical practice today. All these drugs are known to produce gastro intestinal lesions. In the present study we found that aspirin, indomethacin and phenylbutazone caused gastric mucosal damage in 90.9%, 100%, respectively while ibuprofen and paracetamol caused gastric mucosal damage in 33.3% and 37.5% respectively. Thus latter two drugs were safer NSAID's. Further more we have demonstrated that endoscopic monitoring of the patients on NSAID's is a sensitive method of early detection of gastric mucosal damage. This monitoring may be particularly valuable in high risk subjects on NSAID's. PMID- 2096128 TI - Controlled trial of twice a day versus once a day cimetidine therapy for duodenal ulcer. AB - A randomized controlled trial was carried out to compare the efficacy of conventional 400 mg twice daily dose of cimetidine with single bedtime 800 mg dose, in 40 patients with endoscopically proven duodenal ulcer. At repeat endoscopy after four weeks of therapy, complete ulcer healing was achieved in 78% of patients on twice daily dosage and 79% of patients on single daily dosage. A more convenient single nocturnal dosage of cimetidine is as effective in the treatment of duodenal ulcer as a twice daily dosage in the Indian population. PMID- 2096129 TI - Haemorheology in diabetes. AB - The rheology of blood is disturbed in diabetes due to increased viscosity of blood and decreased deformability of red blood cells. This disturbed haemorheology contributes to diabetic vasculopathy and is reversible with treatment with insulin. PMID- 2096130 TI - "Holiday heart" syndrome. PMID- 2096131 TI - Statistics for clinicians. 2. Nominal data (I). AB - Nominal data consist of items assigned to well defined classes. They are presented as a proportion or percentage of the total. From a sample percentage we can estimate the population percentage with a desired degree of confidence, using standard error of the percentage as a measure of chance variation. We can compare the difference in percentage between two groups by means of the z-test or the chi square test. If the number of observations is less than 40, Fisher's test is preferable to the chi-square test. When chi-square test is done on 2x2 tables, Yates' correction is recommended. For tables larger than a 2x2, Yates' correction is not used. When testing paired data for significance of difference, we need to use McNemar's modification of Chi-square test. Chi-square test is useful not only to test the significance of differences but also to test the significance of an association between attributes. PMID- 2096132 TI - Axillary artery thrombosis following heavy isometric exercise. PMID- 2096133 TI - Electrocardiographic manifestations following household electric current injury. AB - Electrocardiographic monitoring of a 24 year old male, who sustained household electric current injury, showed low voltage ECG complexes, varying degrees of atrioventricular (AV) blocks, and ventricular fibrillation. The low voltage ECG complexes and varying AV blocks disappeared spontaneously and ventricular fibrillation reverted to normal after cardioversion. PMID- 2096134 TI - Capsular involvement and sensorimotor stroke with posterior cerebral artery territory infarction. AB - The traditional concept of a clear demarcation between the vascular supply of the internal capsule and the thalamus cannot be regarded as absolute. Two cases of sensorimotor stroke due to posterior cerebral artery territory infarction are described, with CT evidence of internal capsular involvement. PMID- 2096135 TI - Retino-cephalic vascular malformation. AB - Unilateral vascular malformation of the retina, brain and parts of the face constitute a rare syndrome named after Wyburn-Mason or as Bonnet-Dechaume-Blanc syndrome. We report this case because of its rarity. PMID- 2096136 TI - Vertebral compression fracture. An unusual presentation of childhood acute lymphoblastic leukaemia. AB - Vertebral compression fracture is a rare presenting feature of childhood acute lymphoblastic leukaemia. These cases are often characterized by indicators of good prognosis and show a relatively good treatment outcome. PMID- 2096137 TI - Idiopathic ventricular tachycardia in a young man. PMID- 2096138 TI - Jaccoud's arthritis. AB - A 16 year old girl with multivalvular heart disease and recurrent episodes of polyarthritis with correctable deformities of hands and feet fitting into that of Jaccoud's arthritis is reported. The condition is rare and often difficult to differentiate from rheumatoid arthritis. PMID- 2096140 TI - Non-compressive thrombotic obstruction of superior vena cava. PMID- 2096139 TI - Acute paralysis due to barium carbonate. AB - Poisoning due to barium carbonate (rat poison) resulting in areflexic quadriplegia and respiratory muscle paresis in a young patient is described. The various effects of barium salts on the human body and their treatment are highlighted. PMID- 2096141 TI - Paget--Schroetter's syndrome. AB - Primary thrombosis of the subclavian axillary veins is known as Paget Schroetter's syndrome. A 35 year old male with classical features of this syndrome is being reported. Antecubital venogram showed bilateral subclavian thrombosis. PMID- 2096142 TI - Gustatory sweating and diabetes mellitus. PMID- 2096143 TI - A study of blood cations in untreated cases of essential hypertension. PMID- 2096144 TI - Methaemoglobinaemia--a rare cause of myocardial ischaemia. PMID- 2096145 TI - Subgaleal haematoma following hair pulling. PMID- 2096146 TI - Effect of antitubercular treatment and radiotherapy on Aspergillus precipitin seropositivity in a concomitant case of pulmonary tuberculosis and bronchogenic carcinoma. PMID- 2096147 TI - Budd-Chiari syndrome: a not so rare presentation of renal cell carcinoma. PMID- 2096148 TI - [Conservative restoration with composite resins]. AB - At the beginning of the century the radical approach to treatment of an occlusal surface carie of a molar were related to the principles developed by G.V. Black. Extension for prevention in the occlusal fissures, whether they were decayed or not, respected the needs of that era. Those ideas were based on the epidemiology of dental caries and mechanical properties of the filling materials in use to treat them. The parameters of treatment have changed, the reality is not the same. Nowadays, conservative composite resin restorations, demand a less destructive approach for small carious pit and fissure lesions in both the primary and permanent dentitions. PMID- 2096149 TI - The evolution of dental esthetics. AB - Dental esthetics has been based for a long time, on time-honoured theories where the restored or replaced teeth had to match the face shape while providing due respect to the sex, the age and the personality of the patient. Most of these theories have since been disproved and the standards of dental esthetics have been revised following surveys of naturally perfect smiles and patients' preferences. Guidelines are presented in a sequence of 5 easily applicable steps with the objective of creating the right smile for the right patient. PMID- 2096150 TI - [Esthetics in multiband orthodontics]. AB - It is a known fact that many patients who need major orthodontic treatment, simply refuse treatment for reasons related to the esthetics of fixed appliances. These refusals, which occur more often among adults, usually jeopardize the patient's entire treatment plan, and in the long run will endanger the patient's oral health. This article reviews the different alternatives which are available, in order to resolve this major inconvenience which some people tend to have when they need fixed orthodontic appliances (braces). In each case, their advantages and inconveniences, and their indications and contra-indications are described. PMID- 2096151 TI - [Closing diastemas with direct technic]. AB - Diastema closure by simple direct techniques has to take advantage of modern photo-cure systems. This paper reviews the basic concepts of diastema closure and describes a technique that does not necessitate the use a conventional matrix. PMID- 2096152 TI - [The single implant restoration: surgical-restorative relations]. AB - Single tooth replacement using an implant is a relatively new technique. During a study at Universite de Montreal, the esthetic appearance of a single tooth restoration was directly related to the presurgical evaluation and to the implant placement. The goal of this article is to enumerate the clinical requirements and to illustrate the prosthetic results in relation to implant placement. PMID- 2096153 TI - Aesthetics and osseointegration for the completely edentulous. AB - The completely edentulous patient who has been fitted with osseointegrated implants poses new challenges for the restoratie dentist. Besides having to make up for loss of teeth and alveolar bone, the prostheses have to provide function and aesthetics, and be designed to facilitate oral hygiene procedures. The metal superstructure should be strong, have a passive fit, be resistant to corrosion and be easy to clean. Three designs are proposed: the sanitary bridge, the aesthetic bridge and the removable overdenture. The patient's expectations regarding function and aesthetics should be assessed initially by the restorative dentist. General principles of aesthetics in complete dentures are still to be followed: proper upper anterior tooth selection (shape and shade), and correct tooth positioning in relationship to lip line, smile line and profile. Lower teeth should be level with the lower lip and the retromolar pad. Success is based on the patient's capacity to adapt and the dentist's sound application of basic principles. PMID- 2096154 TI - Pulsatile secretion of luteinizing hormone in agonadal men before and during testosterone replacement therapy. AB - We have reevaluated the question regarding the pulsatile pattern of LH secretion in agonadal men before and following testosterone replacement therapy. Five normal males were used as a reference group and four agonadal men were studied before and during replacement therapy with testosterone enanthate. All the subjects were sampled every 5 min for 12 h (08:00 to 20:00). Data were analyzed using the statistically based and validated pulse detection program DETECT. The normal subjects showed an LH pulse frequency of 10.2 +/- 1.7 peaks/12 h (mean +/- SEM) and a mean duration of 48.8 +/- 14 min, while in agonadal patients without testosterone replacement the frequency of LH peaks (27.5 +/- 2 peaks/12h) was significantly higher than for normal subjects (p less than 0.05), and the mean duration of peaks was lower than in controls (17.2 +/- 1.2 min; p less than 0.01). Following chronic testosterone enanthate replacement therapy (200 mg im every two weeks) these patients showed an increase in the duration and a significant reduction in the frequency of LH peaks (from 27.5 +/- 2 to 18.2 +/- 2.1 peaks/12 h; p less than 0.01) but pulse frequency remained significantly higher than for normal subjects (p less than 0.01). This finding is independent of the choice of p values for false positive detection rate (p = 0.01 or p = 0.005), but it does depend on sampling frequency and is influenced by large (four fold) changes in the thresholds for peak detection. Using a "discrete deconvolution" technique we estimated the instantaneous secretory rate (ISR) for the two groups of patients. The results using ISR corroborated the findings obtained using analysis of observed plasma LH measurements. ISR computation also showed that the duration of the secretory events of the gonadotropes is significantly shorter (p less than 0.01) than the one estimated on plasma concentration, both in normal subjects and in agonadal patients before and during testosterone administration. IN CONCLUSION: LH pulse frequency observed in basal conditions in agonadal men was much higher than previously reported in primary testicular failure; during conventional testosterone replacement therapy LH pulse frequency of agonadal men was significantly reduced but still higher (p less than 0.01) than in normal men. This finding is probably related to the subnormal plasma levels of testosterone found in agonadal men during the replacement therapy; the analysis of data using a sampling interval of 10 min gave results similar to previous reports, confirming that the choice of sampling interval can markedly affect the evaluation of frequent LH pulsatile secretion. PMID- 2096155 TI - Resistance to insulin suppression of plasma free fatty acids in liver cirrhosis. AB - Insulin action on carbohydrate metabolism is known to be reduced in liver cirrhosis. However, little is known about the effect of insulin on free fatty acid (FFA) metabolism in these patients. To investigate this aspect we performed a two-step insulin euglycemic clamp in 11 cirrhotic patients and 6 controls. Insulin was infused at 0.25 mU/Kg min from 0 to 100 min and at 1 mU/Kg from 100 to 200 min. The FFA lowering capacity of insulin was studied during the first step; the glucose metabolizing capacity (M) was evaluated during the second step. In the cirrhotic patients, the M value was lower than in controls (3.91 +/- 0.48 vs 7.75 +/- 1.09 mg/kg/min, respectively). During the low insulin infusion, FFA and glycerol plasma levels were decreased in both groups. However, the ability of insulin to suppress plasma FFA and glycerol was lower in cirrhotics than in controls. In fact, at 100 min, FFA were 50% of basal values in cirrhotics and 20% in controls (p less than 0.01), while glycerol plasma levels decreased to 70% of basal values in patients and to 56% in controls. The slope of the linear regression obtained between Ln-FFA concentrations vs time was significantly less in cirrhotic patients than in controls (p less than 0.001). In addition, a positive correlation was found between the M value (r = 0.70; p less than 0.01) and the slope of the Ln-FFA in each patient. These findings suggest that in cirrhotic patients the effects of insulin on both FFA and glucose metabolism are reduced. PMID- 2096157 TI - Evaluation of clonidine suppression and various provocation tests in the diagnosis of pheochromocytoma. AB - Recent investigations have shown that the widely used clonidine suppression test is sometimes fallible for the diagnosis of pheochromocytoma. A comparative assessment was made of the following suppression and provocation tests, the clonidine suppression test, and the glucagon, metoclopramide, and naloxone provocation tests. The assessment was performed in 6 patients with pheochromocytoma and in 19 patients without pheochromocytoma who were initially suspected of harboring a tumor. BP response did not predict the presence of pheochromocytoma in any test. Plasma norepinephrine (NE) concentrations determined at 120 and 180 min after oral 150 micrograms of clonidine gave false negative results in 2 of the 5 patients with pheochromocytoma tested. Both plasma NE and epinephrine (E) concentrations were measured before and sequentially after each provocative agent. Neither NE nor E responded to 1 mg of glucagon iv in 2 of the 4 patients with pheochromocytoma tested. Determination of the peak level, peak increment, and % peak increment of NE and E following 10 mg of naloxone iv did not distinguish the two groups. The % peak increments of both NE and E in all 4 patients with pheochromocytoma given 5 mg of metoclopramide iv exceeded the mean + 3 SD values of the patients without pheochromocytoma (25 + 28% for NE, and 25 + 42% for E). These results suggested that, when performed with judicious patient selection (ambiguous plasma or urinary catecholamine levels), the measurement of plasma catecholamines in response to metoclopramide can be a useful adjunctive tool in the diagnosis of pheochromocytoma. PMID- 2096156 TI - Differential levels of thyroid peroxidase and thyroglobulin messenger ribonucleic acids in congenital goiter with defective thyroglobulin synthesis. AB - The biosynthesis of thyroid hormones requires iodide, thyroid peroxidase (TPO), thyroglobulin (Tg) and H2O2. We have studied two sisters with congenital large goiters and hypothyroidism. Perchlorate tests were negative. Serum T3 and T4 were decreased, TSH was increased and Tg was within the lower limit of normal. Biochemical and molecular studies were performed on goiter samples obtained after surgery. Tg content in both tissues was negligible. Paper chromatography of labeled iodocompounds showed a decrease in T4, and the presence of a pronase/pancreatin-resistant iodoprotein. TPO activity was normal in the tissues. Sephacryl S-300 gel filtration demonstrated labeled iodoalbumin-like protein and the absence of a Tg peak. Salting out studies of soluble protein fraction gave an abnormal pattern. Agarose gel electrophoresis showed the presence of an iodoalbumin-like protein and the absence of Tg in the tissues. This last finding was confirmed by immunoelectrophoresis. The Tg and TPO mRNAs levels were also analyzed. Dot-blot hybridization studies with pM5 (TPO cDNA) and phTgM2 (Tg cDNA) probes showed increased and decreased signals, respectively. The increase in TPO mRNA can be explained as a compensatory mechanism vis a vis an increase in serum TSH caused by decreased serum T3 and T4 due to the impairment in Tg mRNA. The Tg mRNA of both patients was further studied with four different probes covering 5' and 3' regions (phTgM1, phTgB1, phTgB2 and phTgB3). Hybridization was observed with all four probes, thus excluding a dramatic deletion defect. Northern transfer showed a clear signal of hybridization with the phTgB1 probe in the 8-9 Kb range. We may conclude that the biochemical and molecular abnormality of these patients is characterized by a decrease of Tg mRNA and of Tg translation. PMID- 2096158 TI - Gangliosides and phospholipids in human thyroids responsive and unresponsive to thyrotropin. AB - The patterns of gangliosides and phospholipids and their relation to TSH response were examined in twenty-six malignant thyroid tumors (4 follicular, 6 papillary, 5 medullary, 11 anaplastic carcinomas) and thirty-six hyperplastic goiters. Thirteen thyroid tissues adjacent to benign tumors with no evidence of macroscopic or microscopic abnormalities were used as normal tissue. In normal thyroids the major ganglioside was GD3 (44%) and GM3 was the second ganglioside (20%). In minor amounts GD1a (8.6%), GD1b (6.2%), GT1b (5.7%) and GM1 (5.6%) were present. In hyperplastic goiters and in follicular carcinomas the patterns of gangliosides were similar to that of normal tissue except for GM3 which, in the last tissue, was higher (34%). In papillary carcinomas low levels of GM3 (11%) and GT1b (0.8%) with a high level of GD1b (12.6%) were found. In anaplastic carcinomas GM3 was very high (47%) whereas GD3 was low (18%). In these tumors also a high percentage (14.0%) of GD1a was found. In medullary carcinomas the lowest levels of GM3 (4%) with the highest level of GD3 (64%) were found. Although large differences of the gangliosides distribution were clearly encountered in the various pathological human thyroid, no correlation between lack of TSH response and some individual ganglioside could be made. No differences in the individual phospholipid in the various tissues studied were found. PMID- 2096159 TI - Two cases of Graves' disease with antithyroid hormone antibodies: implication on the role of thyroglobulin as an antigen. AB - We have experienced two cases of Graves' disease with antithyroid hormone autoantibodies (Case 1: anti-T4; Case 2: anti-T3) who finally underwent subtotal thyroidectomy after antithyroid drug treatment. Using serial sera obtained before and after operation, the correlation between titers of antithyroglobulin (anti Tg) and anti-T4 or anti-T3 autoantibodies was examined in each case. There was a significant positive correlation between titers of anti-T4 (Case 1, r = 0.90, p less than 0.05), or anti-T3 (Case 2, r = 0.64, p less than 0.01) and anti-Tg antibodies. Using the homogenate of the thyroid tissue, it was found that the sole iodoprotein in the thyroid gland in each patient was 660 KDa Tg. In addition, Tg purified from the thyroid gland from Case 2 showed different immunological activity with normal Tg in two out of four murine monoclonal anti Tg antibodies tested. On the other hand, Tg from Case 1 had identical immunological activity with normal Tg in every four monoclonal antibodies. These results are consistent with the view that the antigen responsible for the development of antithyroid hormone autoantibodies is Tg, at least in our two cases. The reason for the persistence of anti-T3 autoantibodies in Case 2, despite the subtotal thyroidectomy, could be due to some unidentified structural abnormalities of Tg which was detected only by the monoclonal anti-Tg antibodies. PMID- 2096160 TI - Growth hormone therapy in a poorly growing child with hypophosphatemic rickets. AB - We treated a 10 6/12 year old prepubertal male with hypophosphatemic rickets, who was growing poorly despite appropriate treatment with calcitriol and phosphate, with exogenous growth hormone (for an initial trial period of 4 months, followed by 14 months of continuous treatment at a dose of 4 IU three times weekly) even though his growth hormone testing proved to be normal. His growth rate increased significantly during treatment with synthetic growth hormone (from a basal rate of 3.9 cm/yr to 9 cm/yr during the first 4 months of therapy and from 2.7 cm/yr to 6.0 cm/yr during next 14 months of treatment) and his predicted adult height increased as well. Slight metabolic changes were detected in this patient during treatment, with an increase in serum phosphorus and a decrease in twenty-four hour urine calcium concentrations. It would seem reasonable to evaluate the growth hormone status of children with hypophosphatemic rickets who are growing poorly despite appropriate therapy with calcitriol and phosphate and to consider a trial period of therapy with growth hormone in some of them. PMID- 2096162 TI - Confirmation of high blood flow rates through 150 mu filter/high-flow tubing. AB - Many new products designed to assist in rapid blood infusion are appearing. Some highly touted and routinely used devices for intravenous (IV) infusion have recently been shown to be, at least in part, defective. A tubing with an in-line 150 mu filter (150 mu High-Flow Blood Filter; Saftifilter Blood Administration Sets; Cutter Biological, Berkeley, CA 94710) has recently been introduced to facilitate rapid blood transfusion. It is claimed that at least 8.5 units of blood can be rapidly run through each set before replacement is necessary. To test this under simulated clinical conditions, four sets of ten random units of outdated erythrocytes at 4 to 9 degrees C were each admixed with 250 mL 70 degrees C 0.9 NaCl and infused through the system under a constant 300 mmHg pressure. Two sets infused through unmodified tubing flowed at an average of 25 mL/sec (1500 mL/min) before there was an appreciable slowing of the flow rate. Two sets with 8 Fr catheters attached infused at an average of 22 mL/sec (1320 mL/min) before there was an appreciable slowing of the flow rate. Even after the flow slowed, the 9th and 10th units infused at an average greater than 10 mL/sec (600 mL/min). The tubing/filter exceeded the manufacturer's published claims. This tubing/filter appears to be one element that could be an effective component of a high-flow infusion system. PMID- 2096161 TI - Pseudohyperaldosteronism from liquorice-containing laxatives. AB - Four cases of pseudohyperaldosteronism due to chronic ingestion of liquorice containing laxatives are described. All patients had hypertension and hypokalemia with suppression of plasma renin activity and aldosterone; the diagnosis was based only on retrospective grounds. In patients with hypokalemia and hypertension a possibility of such a cause must be excluded to avoid unnecessary diagnostic procedures. PMID- 2096163 TI - Microscopic hematuria and calculus-related ureteral obstruction. AB - The evaluation of patients with ureteral calculi in the emergency department has historically included urinalysis (UA) and intravenous pyelograms (IVP). This retrospective study was done to determine if a statistically significant relationship existed between the degree of calculus-related ureteral obstruction, proven by IVP, and the presence or absence of microscopic hematuria. Urine red blood cells were recorded as less than 3 rbc/hpf (negative) or greater than or equal to 3 rbc/hpf (positive). IVPs were recorded as nonsevere or severe. IVP criteria were based on the presence or absence of extravasation, greater than 2 hour ureteral filling times, and a numerical scoring system of 1 to 4 for ureteral or calyceal dilatation and nephrogenic effect. Eighty-nine men (72%) had non-severe obstructions and 34 (28%) had severe obstructions. Twenty-five women (68%) had nonsevere obstructions and 12 (32%) had severe obstructions. Of the 28 patients with normal UAs, 11 had severe ureteral obstructions and 17 had nonsevere ureteral obstructions. There were no statistically significant differences between the presence or absence of significant microscopic hematuria and the presence or absence of severe ureteral obstruction. Microscopic hematuria is neither sensitive nor specific in determining the degree of calculus-related ureteral obstruction. PMID- 2096164 TI - Radiograph ordering: agreement between the triage nurse and the physician in a pediatric emergency department. AB - We hypothesized that the triage nurse in a busy pediatric emergency department (ED) could accurately order radiographs, ultimately reducing patient waiting time. Protocols utilized to reduce patient waiting time are of importance in busy emergency departments. All patients registering at the ED of the Children's Hospital in a one-week period were entered into the study. The triage nurse documented whether they would send the patient for a radiograph, if allowed to, and were asked to designate a specific radiograph. The radiographs that were actually ordered by the physicians were subsequently obtained from radiology records. Data were analyzed for agreement beyond chance (kappa), positive (PPV) and negative predictive values. The results showed excellent agreement for extremity radiographs and poor agreement for nonextremity radiographs. PMID- 2096166 TI - Beriberi heart disease in a schizophrenic with an unusual diet. AB - A 37-year-old male presented with peripheral edema of sudden onset. Other signs of heart failure were absent. Subsequent evaluation revealed that the patient was a schizophrenic whose diet consisted almost entirely of carbohydrates. A clinical diagnosis of beriberi heart disease was made and the patient improved dramatically within several days of thiamine supplementation. The presentation of beriberi heart disease in developed countries is discussed. Emphasis is placed on food faddists and psychiatric patients in whom clinical findings may be subtle or absent. PMID- 2096165 TI - Wound infection due to fresh water contamination by Aeromonas hydrophila. AB - We report the case of a 24-year-old man who sustained a scalp laceration in a diving accident. His wound became infected, and he was treated with an oral cephalosporin, with subsequent progression of the infection. Cultures subsequently grew Aeromonas hydrophila. Many strains of Aeromonas are not sensitive to the antibiotics commonly used for wound infections. Aeromonas must be suspected as a pathogen in all wounds occurring in fresh water if proper treatment is to be initiated. PMID- 2096167 TI - A simple sore throat? Retropharyngeal emphysema secondary to free-basing cocaine. AB - A case of retropharyngeal emphysema associated with drug abuse is presented. Although chest symptoms of pneumomediastinum have been widely reported with substance abuse, pain localized to the neck is rarely described. In the present case, localized dysphagia was the only complaint, and no free air could be demonstrated within the thorax. For uncomplicated cervical emphysema or pneumomediastinum due to substance abuse, extensive workup may be unnecessary, and conservative therapy, including administration of 100% oxygen and observation is recommended if resolution is prompt. PMID- 2096168 TI - Traumatic rupture of the stomach after Heimlich maneuver. AB - Fatal complications following the performance of the Heimlich maneuver have been reported. A 76-year-old woman presented to the emergency department with signs of respiratory distress, abdominal pain and distension one day after airway obstruction and subsequent resuscitation. Despite successful immediate laparotomy and repair of a ruptured stomach, she later succumbed to the sequelae of aspiration of gastric contents and dehiscence of the gastric tear. This is the 4th case of stomach rupture and the 7th reported fatal complication following the Heimlich maneuver. It is recommended that persons who undergo the Heimlich maneuver be examined and observed by a physician, as soon as possible, to rule out complications. PMID- 2096169 TI - Cardiopulmonary arrest following an infusion of calcium 2-amino ethanol phosphate. AB - The intravenous infusion of calcium 2-amino ethanol phosphate was coincidental with cardiopulmonary arrest in a 53-year-old woman with a history of multiple sclerosis. Resuscitation was followed by massive hemolysis, renal failure, adult respiratory distress syndrome, shock liver, and disseminated intravascular coagulation. This agent, in use by at least one practitioner in West Germany for the treatment of inflammatory and autoimmune disorders is not FDA approved for use in the United States, nor is clinical investigation underway. It is currently thought to be in use by about 200 practitioners throughout this country as treatment for multiple sclerosis. It is apparently obtained in West Germany and brought illegally into the United States. This is the first known report of an adverse drug reaction associated with the use of this product. PMID- 2096170 TI - Acute cor pulmonale secondary to metastatic tumor to the heart: a case report and literature review. AB - Metastatic tumors to the heart are becoming more common due to improved survival afforded by advanced treatment of malignancies. Their presence should be sought in a cancer patient who develops new primary cardiac symptoms. We present a case of a 50-year-old woman who succumbed to acute cor pulmonale secondary to metastatic laryngeal carcinoma to the right ventricle with subsequent tumor emboli to the pulmonary vasculature. PMID- 2096171 TI - Cough-variant asthma in children and adults: case reports and review. AB - Two cases of cough-variant asthma are presented, one in an adult and one in a child. We discuss the diagnosis, treatment, and course of this common, yet often unrecognized entity. The keys to diagnosis are a typical history, clinical suspicion, and subsequent response to bronchodilator therapy. Treatment of cough variant asthma is no different from that of classic asthma. PMID- 2096174 TI - Interpretation and clinical significance of the QRS axis of the electrocardiogram. AB - The frontal plane QRS axis of the standard 12-lead electrocardiogram (ECG) is easily and accurately measured by the clinician. A simple method of estimating this axis is discussed. This axis is age-dependent. We reviewed the literature to determine if evidence exists of an association between an "abnormal" QRS axis and clinically significant myocardial disease. We also examined the literature for clinical correlation of a "normal" QRS axis with the absence of myocardial pathology. We found that although an abnormal QRS axis (falling outside the limits of +30 degrees and +90 degrees) occurs in a small number of normal individuals, its presence should prompt a thorough evaluation of all the parameters of the ECG to look for myocardial disease. PMID- 2096173 TI - The beginnings of urban ambulance service in the United States and England. AB - Urban ambulance systems emerged in the second half of the 19th century as an outgrowth of military experiences in both Europe and America. Developing first in cities such as Cleveland and New York, these systems quickly adapted to the urban environment, and modifications in ambulance construction and procedures soon followed. Since first-aid texts for urban ambulances were rare, military texts on battlefield medicine were adapted to emergency medicine in civilian accidents. PMID- 2096175 TI - Making tympanocentesis [correction of tympanpanocentesis] easier. AB - Tympanocentesis can be of great value in identifying the etiologic agent of acute otitis media. Unfortunately the trepidation with which clinicians approach this procedure may limit its application. This report of a method of tympanocentesis suggests a short-cut using instruments readily available in emergency departments and in many doctors' offices. The manuscript describes a means of stabilizing the needle in the middle ear during aspiration and details a simple method of handling middle ear aspirates which should ensure the viability of middle ear bacteria until they reach the laboratory. PMID- 2096176 TI - Artistic and scientific revolution. PMID- 2096172 TI - "Designer drugs"--a current perspective. AB - Since the late 1970s, in an effort to quench the ever burgeoning appetite for pharmacological substances of abuse and to satiate their own need for profit, unscrupulous chemists have set up clandestine laboratories to produce and market new drugs for street sale. Using fairly common industrial chemicals, they have altered or modified preexisting controlled substances such as fentanyl, meperidine, mescaline, amphetamine, and phencyclidine, producing derivatives of these parent compounds that, up until 1986, were able to temporarily elude the guidelines of the Federal Controlled Substances Act due to their new and unique chemical structures. Unsuspecting users continue to use the drugs recreationally. This article will present a comprehensive review of these "Designer Drugs" looking at historical data, pharmacokinetics, treatment, abuse trends, and some of the more recent additions to the social pharmacopoeia. PMID- 2096177 TI - Hospital mergers: legal and personal implications for emergency physicians. AB - In east central Illinois over the last three years, three hospitals in which the authors were contracted as emergency physicians have been in various stages of merger with nearby hospitals. In all, six hospitals will be merged into three "medical centers." This is a basis of experience to be shared with other emergency physicians, as consolidation of health care facilities seems to be a wave of the future due to financial constraints of the health care setting. Lessons to be learned from these experiences involve many issues, including work contract, malpractice insurance payment, physician and nurse staffing, and public information problems. PMID- 2096178 TI - The etiology of medical gridlock: causes of emergency department overcrowding in New York City. AB - Overcrowding of emergency departments in New York City is the most apparent symptom of a crumbling health care system. There is a growing need for the care of a largely impoverished population suffering from an increasing prevalence of AIDS, substance abuse, and psychiatric disease. Institutions crippled by critical shortages of inpatient beds and nurses lack the resources to meet this rising demand. Although the epidemic of medical gridlock began in New York City, it is spreading rapidly to involve other areas of the country. Short-term efforts to resolve this crisis have thus far been unsuccessful. Long-range solutions are likely to be costly and may require a reconfiguration of societal health care priorities. PMID- 2096179 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: emergency medical services. AB - Emergency Medical Services are an area of special interest in emergency medicine. Many emergency physicians are called upon to direct, train, or manage emergency medical services. Residents training in emergency medicine have a need for a defined curriculum in emergency medical services. Residency training should provide a basic foundation in EMS including on- and off-line medical control, medicolegal aspects, communications, disaster management, and EMS history, structure, and function. The resident must gain experience through on-scene observation, EMT/Paramedic education, medical direction, and quality assurance activities. This paper is one in a continuing series of goals and objectives to direct resident training in off-service rotations. Specific resources, learning objectives, and experiences are suggested. PMID- 2096180 TI - Immunogenetic aspects of human thyroglobulin-reactive T cell lines and hybridomas. AB - The in vitro proliferative response to T cells primed with human thyroglobulin (Tg) was compared in 11 independent haplotypes on B10 background. B10.K and B10.S mice were the most responsive, whereas, with the exception of B10.PL (H-2u), all other B10 congenics were intermediate responders. The two best responders to in vitro challenge with human Tg, of the k and s haplotype, are the same as those showing H-2-linked susceptibility to induction of experimental autoimmune thyroiditis (EAT) with mouse Tg. Since shared epitopes on human and mouse Tgs have been shown to be thyroiditogenic by adoptive transfer studies in CBA (H2k) mice, the findings indicate that shared epitopes may be studied in appropriate (i.e. EAT-susceptible) strains of mice. Therefore, we proceeded to develop methods to produce T-cell lines and hybridomas to human Tg in B10.K and B10.S mice, test their cross-reactivity to heterologous Tgs and their Ia restriction patterns. By using antigen-presenting cells from recombinant strains, we identified restriction elements encoded by the I-A subregion alone and a combinatorial molecule from the I-A/I-E subregions. PMID- 2096181 TI - Increased interleukin-2 receptor affinity in normal HLA A1 B8 DR3 subjects. AB - Twenty-two subjects (11 HLA A1 B8 DR3, 11 non-A1 B8 DR3) were tested for the capacity of their lymphocytes to express Tac molecules and interleukin-2 (IL-2) receptors (quantified using radiolabelled IL-2) after mitogen stimulation. Ten of these subjects (five A1 B8 DR3 and five non-A1 B8 DR3) were also tested for the ability of their lymphocytes to proliferate under IL-2 stimulation. A1 B8 DR3 subjects express a normal number of high-affinity IL-2 receptor sites, but the affinity of these receptors sites is significantly increased. Unexpectedly, A1 B8 DR3 lymphoblasts show a lower response to IL-2 than non-A1 B8 DR3 for high doses of recombinant IL-2. PMID- 2096182 TI - Characterization of MHC ancestral haplotypes associated with insulin-dependent diabetes mellitus: evidence for involvement of non-HLA genes. AB - Insulin-dependent diabetes mellitus (IDDM) is associated with several DR3- or DR4 containing ancestral haplotypes (AHs). Using pulsed field gel electrophoresis (PFGE), long range maps of 35 haplotypes have been derived and classified. Two diabetogenic DR3-containing AHs (8.1 and 18.2) possess deletions in the central non-HLA region; these have not been found on non-diabetogenic AHs tested to date. In addition, 8.1 and 18.2 also carry other deletions not found on other AHs. Three DR4 containing AH lack a Not I site, which may imply excision of an unidentified gene. These and other data suggest that deletions may be relevant to the pathogenesis of autoimmune disease, possibly through causing quantitative differences in autoimmune responses involved in IDDM. The MHC contains several regions of potential interest in relation to susceptibility to IDDM; these may explain the association with only certain DR3- and DR4-carrying AH and DR3,4 heterozygosity in terms of cis and trans interactions. On the other hand, the class II region may be particularly important in protection. PMID- 2096183 TI - Characterization of soluble HLA molecules in sweat and quantitative HLA differences in serum of healthy individuals. AB - Soluble class I molecules were immunoprecipitated from human sweat and serum using the BB7.7 monoclonal antibody (mAb) coupled to immunomagnetic beads. Molecules were analysed biochemically on SDS-PAGE gels and finally by ID isoelectric-focusing (IEF). Serum- and sweat-HLA IEF-band patterns of the same individual were fully identical, showing that HLA excreted in sweat possess polymorphic structures like those in serum. Quantitatively, we used a highly sensitive competitive enzyme-linked immunosorbent (ELISA) assay to determine soluble class I concentrations. The first group was that of non-HLA-A9 and -Bw62 sera, which were found to contain HLA levels with a mean concentration of 0.82 +/ 0.63 microgram/ml (n = 44). However, sera that were HLA-A23 or -24 (splits of HLA-A9) contained higher levels, with a mean of 3.2 +/- 0.94 microgram/ml (n = 20). Similarly, HLA-Bw62 individuals had a higher mean of 2.05 +/- 0.65 micrograms/ml (n = 10). The difference of the HLA-A9 group to the first group was statistically highly significant, P less than 0.0001, and that of the HLA-Bw62 to the first was also significant, P less than 0.004. Individuals who were both HLA A9 and -Bw62 (n = 5) did not express significantly higher levels than those who only had one of these specificities. Sweat HLA levels had a mean of 0.42 +/- 0.4 microgram/ml (n = 10). These results show for the first time that soluble class I peptides are excreted in relatively high concentrations in sweat and possess polymorphic structures identical to those of serum HLA and that serum HLA levels are allotype dependent. PMID- 2096185 TI - Chemical dependency and drug testing in the workplace. AB - Urine testing for drug use in the workplace is now widespread, with the prevalence of positive drug tests in the work force being 0% to 15%. The prevalence of marijuana use is highest of the illicit drugs being tested. Highly prevalent drugs can be reliably tested. Although it is prudent to rid the workplace of drug use, there is little scientific study on the relationship of drug use and workplace outcomes, such as productivity and safety. Probable-cause testing and preemployment testing are the most common applications. Random testing has been less accepted owing to its higher costs, unresolved legal issues, and predictably poor test reliability. Legal issues have focused on the right to privacy, policy agreements, discrimination, and the lack of due process. The legal cornerstone of a good program is a policy that is planned and agreed on by both labor and management, which serves both as a contract and as a procedure in which expectations and consequences are known. Moreover, NIDA is certifying laboratories doing employee drug testing. Testing methods, when done correctly, are less prone to error than in the past, but screening tests can be defeated by adulterants. Although the incidence of false-positive results is low, such tests are less reliable when the prevalence of drug abuse is also low. PMID- 2096184 TI - Identifying and responding to drug abuse in the workplace: an overview. AB - A realistic program for managing drug abuse in the workplace requires a clear understanding of the nature and effects of both licit and illicit drugs, as well as a knowledge of reliable methods for identifying and responding to both industry and individual needs. This article reviews the nature and effects of psychoactive drugs and discusses the medical steps to be taken when they are being abused. In addition, an overview of the means for identifying workplace drug abusers is presented. Testing methods and procedures are described, and such problems as false-positive and false-negative test results are clarified. The formation of corporate drug abuse policies is discussed and a continuum of industry interaction with health and drug abuse treatment professionals is presented. The roles of industry medical review officers, employee assistance programs, and other pertinent groups and individuals are also discussed. PMID- 2096186 TI - Drug-testing methods and reliability. AB - The methods used by laboratories to analyze urine collected from employees are described. Federally designed procedures designed for analyzing government employee samples have become the highest standard for performing such tests, although at present there are no guidelines that specifically address drug testing in the private sector. Samples and analysis should be handled in a manner that ensures that test results are legally defensible. Enzyme immunoassay is the technique used to perform the initial test on these samples. Positive test samples identified by this method are tested again by gas chromatography-mass spectrometry. Potential problems with these analytical methods, additional safeguards, and data demonstrating the reliability of this approach are presented. PMID- 2096187 TI - The medical review officer. AB - The role and responsibilities of the medical review officer are considered in relation to drug testing in the workplace. Knowledge of substance abuse disorders, pharmacology and toxicology, laboratory techniques for screening and confirmation, forensic collection techniques, and the relevant rules and regulations that govern drug testing is essential. The means for detecting adulterated urine samples are offered, and a procedure for the management of urine-testing results is provided. PMID- 2096188 TI - The medical review officer and workplace drug testing. AB - Rational drug-testing programs attempt to balance the need for accuracy of the process with the need to preserve the rights and dignity of the people being tested. U.S. Department of Transportation regulations prescribe the specifics of how urine specimens are to be collected, how to inform the specimen donor of the process to which he or she will be subjected, and certification of laboratories by the National Institute of Drug Abuse. These guidelines are an effort to assure that each collection site and each laboratory testing the urine of employees adheres to certain basic standards of quality control. PMID- 2096189 TI - Monitoring, reentry, and relapse prevention for chemically dependent health care professionals. AB - Monitoring and reentry programs for chemically dependent health care professionals are increasingly being recognized as important components of recovery efforts targeted at this population. Such monitoring and preventive programs should incorporate certain eligibility requirements, patient-monitoring program contracts, recovery maintenance activities and adjuncts, work-site assessments and reentry recommendations, random body fluid analysis, relapse management, and clear explanations of financial responsibility. Monitoring and reentry programs need to be fully integrated within the spectrum of resources available to health care professionals. PMID- 2096190 TI - Medicines and drug testing in the workplace. AB - Drug testing at work is rapidly becoming the standard in the United States. For drug testing to fulfill its promise as a vital part of the effort to end the drug abuse epidemic, it is essential that the tests be reliable so that people who are not using drugs are not falsely accused and that legitimate medical use of controlled substances not expose employees to harassment or labeling as drug abusers. To merit employee confidence, workplace drug testing needs to be made part of a program that includes these basic elements: (1) a clear and comprehensive policy; (2) secure collection; (3) chain-of-custody procedures; (4) retained positive samples; (5) an initial screening test; (6) a sophisticated confirmatory test; (7) a medical review officer; (8) a retest of retained positive samples in disputed cases; and (9) a system of quality control. In addition, this drug testing program needs to be built on a solid foundation that distinguishes between legitimate use of prescribed medicines and nonmedical drug use. This differentiation is the primary responsibility of the medical review officer. PMID- 2096192 TI - The smoke-free workplace. AB - As the significance of drug use and/or abuse in the workplace is explored, and the public is encouraged to embrace the War on Drugs, policymakers and treatment personnel must not concentrate only on illicit drugs but on licit drugs as well. This article explores the impact of cigarette smoking in the workplace and reviews alternatives for decreasing or eliminating exposure to involuntary smoke in the workplace. PMID- 2096191 TI - Psychiatric diagnoses and perceived health problems in a sample of working Swedes treated with psychoactive medications. AB - Findings of formal and subjective mental health problems among Swedish employees are presented as well as reviews of current Swedish policies on substance abuse and drug screening in the workplace. The focus is on the potential violation of medical confidentiality for employees with legitimate psychoactive drug medications and the lack of evidence linking the detection of various substances with impaired work performance. Data are drawn from a study of a sample of working Swedes, which revealed that approximately 3% reported taking psychoactive medications regularly. This was correlated with increases in long-term sick leave, periods of unemployment, and frequent job changes by both sexes. These workers also scored high for neuroticism, and had high rates of inpatient psychiatric treatment and suicide. With these high rates of formal mental health problems among employees who self-medicate with psychoactive drugs, discriminatory personnel management, including drug screening, jeopardizes confidentiality of treatment and civil rights. PMID- 2096193 TI - To test or not to test? Social welfare versus worker freedom. AB - Workplace testing for drug use is a form of warrantless search for incriminating evidence that if found will lead to an array of sanctions. An argument is presented that such testing is constitutionally impermissible, with two exceptions: (1) employers may use drug testing as a device to screen out prospective employees; and (2) employers may use involuntary workplace drug testing to help employees become drug free, so long as no further sanctions are involved. Of course, should workers accept employment in workplaces with prior existent drug-free rules, they have voluntarily submitted those rules, possibly including drug testing, and the explicit sanctions attached to them. PMID- 2096194 TI - Comparison of the rat pinealocyte ultrastructure with melatonin concentrations during daytime and at night. AB - The aim of this study was to investigate the ultrastructure of rat pinealocyte during daytime (1600 h) and at night (0100 h) and to compare these observations with serum melatonin levels in the same animals. In addition, pineal melatonin concentrations were determined in other animals. Both serum and pineal melatonin concentrations were significantly higher at night than during daytime (34 and 21 times, respectively). Sizes of pinealocytes, their nuclei, and nucleoli, as well as cross-sectional areas of mitochondria and granular endoplasmic reticulum were also higher at night than during daytime, whereas areas of lysosomes, Golgi apparatus, and vacuoles containing flocculent material did not differ at the time points studied. In contrast, the number of dense-core vesicles was higher during daytime. The results of the present study show that morphological patterns of higher metabolic activity of the rat pinealocyte at night when compared to those during daytime correlate with melatonin concentrations. PMID- 2096195 TI - Evidence for an effect of ELF electromagnetic fields on human pineal gland function. AB - A study was carried out to determine possible effects of 60-Hz electromagnetic field exposure on pineal gland function in humans. Overnight excretion of urinary 6-hydroxymelatonin sulfate (6-OHMS), a stable urinary metabolite of the pineal hormone melatonin, was used to assess pineal gland function in 42 volunteers who used standard (conventional) or modified continuous polymer wire (CPW) electric blankets for approximately 8 weeks. Volunteers using conventional electric blankets showed no variations in 6-OHMS excretion as either a group or individuals during the study period. Serving as their own controls, 7 of 28 volunteers using the CPW blankets showed statistically significant changes in their mean nighttime 6-OHMS excretion. The CPW blankets switched on and off approximately twice as often when in service and produced magnetic fields that were 50% stronger than those from the conventional electric blankets. On the basis of these findings, we hypothesize that periodic exposure to pulsed DC or extremely low frequency electric or magnetic fields of sufficient intensity and duration can affect pineal gland function in certain individuals. PMID- 2096196 TI - Chronic administration of pineal peptides change the circadian locomotor activity and time-course of forced swimming in rats. AB - After chronic administration of epithalamin (a pineal peptide drug), an increase in the amplitude and shifts in the acrophase of rat's circadian locomotor activity to late hours were observed. These results were obtained only in rats with low initial amplitude of their circadian rhythm. Epithalamin also changed the time-course of forced swimming and decreased the rhythmic index of depression. These observations suggest that the pineal gland of the rat, via its peptides, may prevent the development of depressive-like events. PMID- 2096197 TI - Sphygmomanometer cuff sizes--new recommendations. PMID- 2096199 TI - Casual urine concentrations of sodium, potassium, and creatine in population studies of blood pressure. AB - The relationships between blood pressure and the concentrations of urinary sodium, potassium and creatinine have been examined using casual urine specimens collected from a random sample of 1,556 men aged 40-59. Partial correlations with systolic blood pressure after adjustment for age, body mass index (BMI), alcohol consumption, and town showed that sodium was not significantly associated with BP, but potassium [r = -0.09 (P less than 0.001)] and creatinine [r = -0.07 (P less than 0.01)] were negatively associated. The sodium/creatinine ratio [r = 0.10 (P less than 0.001)] and sodium/potassium ratio [r = 0.11 (P less than 0.001)] were positively correlated with SBP. Comparable results were found throughout for diastolic pressure. Multiple regression analysis suggested that it was creatinine rather than sodium that was the important component of the sodium/creatinine ratio, and raised the possibility that potassium may play a part in this association because of the strong correlation between potassium and creatinine. Similarly, potassium appeared to be the more important component of the sodium/potassium ratio. The regression coefficients for sodium, potassium, and the sodium/potassium ratio in this study of casual urine samples were found to be similar in direction and magnitude to two large studies using 24 hour urine collections. We suggest that causal specimens may be useful for estimating sodium and potassium intake in population studies. PMID- 2096198 TI - Potassium effects on blood pressure: is the conjugate anion important? AB - Potassium salts, often in the form of KCl, have had variable hypotensive effects in experimental animals and man. The chloride anion has recently been implicated as the hypertensive agent in salt-sensitive hypertension. We therefore hypothesized that non-chloride salts of potassium would have superior hypotensive effects to KCl. In randomized, double-blind fashion, we administered placebo, KCl (75 mmol/day) or potassium citrate (75 mmol/day) to 24 normotensive adult males. In these subjects, neither KCl nor potassium citrate affected blood pressure, despite urinary verification of potassium supplement intake. Thus, in these experimental circumstances, neither potassium nor its conjugate anion were of importance in lowering blood pressure. PMID- 2096201 TI - Blood pressure and physical fitness in a population of children--the Odense Schoolchild Study. AB - This cross-sectional study examined the association between blood pressure and physical fitness in 1,369 children (81.5% of the eligible population) aged 8-10 years participating in the first phase of a primary intervention study with physical training. An inverse correlation between BP and physical fitness was demonstrated, and significant differences have been found between quartiles of distribution of physical fitness in girls with regard to systolic BP and in boys and girls with regard to diastolic BP respectively. Important determinants of physical fitness seemed to be dependent on confounding variables representing body mass index, height, heart rate and age. Our observations suggest that the contribution of confounding variables may explain the relationship between BP and physical fitness in childhood. PMID- 2096200 TI - On the sex ratio of urinary cation excretion obtained from Intersalt and other epidemiological studies. AB - Large differences exist within populations in the dietary intake of nutrients between men and women and these differences are still largely unknown. Using data obtained from the Intersalt study and from other relevant epidemiological studies, the sex ratio of the 24 h urinary excretion of different cations was obtained. Highly significant correlations (P less than 0.001) were found between the 24 h urinary cation and creatinine excretions of men and women. Highly variable sex ratios of 24 h urinary excretion of cations were obtained between populations, presumably due to the different levels of physical activity between men and women. The sex ratio of blood pressure did not correlate with the sex ratio of the 24 h urinary excretion of sodium, potassium, calcium or magnesium, but correlated significantly with the sex ratio of the BMI (P less than 0.01). On a global scale men had a nearly 22% higher urinary excretion of cations than women, pointing towards a 22% higher dietary intake of the cations considered. PMID- 2096202 TI - Blood pressure in a multiracial urban Sudanese community. AB - A study was conducted into blood pressure in a sample of 510 urban Sudanese working in the post office in Khartoum. The mean age was 35 years and 65% of the workers came from Northern Sudan. Cigarette smoking and any consumption of alcohol was commonest amongst those from Southern Sudan. Both systolic and diastolic BPs rose with age. The prevalence of hypertension (140/90 mmHg or greater) was 7.5%. BP levels in this study were lower than those reported in Nigerians or blacks in the Caribbean or the United States. There was a significant positive correlation between SBP and DBP and age, weight, body mass index and duration of residence in the city. These data confirm that hypertension is becoming an important health problem in the Sudan. PMID- 2096203 TI - Reproducibility of ambulatory blood pressure load. AB - Twenty-two hypertensive patients were monitored during two separate drug-free occasions with a Del Mar Avionics ambulatory device. Blood pressure loads (percentage of systolic and diastolic readings more than 140 and 90 mmHg, respectively) and mean BP were measured both to determine their reproducibility and to examine how they correlate with each other. The systolic and diastolic mean awake BPs for day 1 and day 2 were 140/93 mmHg and 140/91 mmHg, respectively, and BP loads were 45%/55% and 43%/54%. Moreover, mean BP loads correlated highly (r = 0.93) with mean BP values taken on the same day. Both ambulatory mean SBP and BP load were highly reproducible (r = 0.87 and 0.80, respectively, during the awake hours), and mean DBP and load were fairly reproducible (r = 0.59 and 0.39, respectively, during the awake hours). Clinically, however, both were consistent from day 1 to day 2. Mean and individual standard deviations also were reproducible for both systolic and diastolic pressures and loads. PMID- 2096204 TI - Placebo effect and adaptation to noninvasive monitoring of BP. AB - Three 24 h ambulatory monitorings of BP were performed at two-week intervals in 21 untreated hypertensives (mean age 38 +/- 10 yrs, 13 males and 9 females). After the first baseline monitoring, the patients were randomised, according to a cross-over design, to one of the following sequences: no therapy to placebo or placebo to no therapy. At the end of each period, noninvasive ambulatory monitoring was performed. Mean +/- SE 24 h systolic (SBP) and diastolic (DBP) pressures recorded at the first monitoring were 129.2 +/- 3.5 mmHg and 81.7 +/- 2.3 mmHg respectively. At the second and third monitorings, mean 24 h BP differences versus baseline levels were -2.9 +/- 1.8 and -4.7 +/- 1.7 mmHg for SBP, and -2.0 +/- 1.1 and -2.7 +/- 1.5 mmHg for DBP. Both SBP and DBP differences at repeated monitorings were significant by analysis of variance (P less than 0.05). No significant effects on BP of treatment sequence or of placebo administration were found. Analysis of covariance showed a significant relationship between initial 24 h BP and subsequent mean 24 h BP differences (SBP: beta = -0.260, DBP: beta = -0.124). ANOVA performed on waking and sleeping BP separately showed the observed differences to be significant only during waking hours. Regression analysis showed that the decrease in 24 h BP at repeated monitorings was significantly related to the extent of 'white coat'-induced BP increase only for DBP (P = 0.022). For both 24 h SBP and DBP, however, a negative correlation between the alarm reaction to the presence of the physician and 24 h BP decrease at repeated monitorings was observed. It is concluded that noninvasive ambulatory monitoring is subject to adaptative phenomena but not to placebo effect. Factors influencing the defence reactions to manual measurements and to ambulatory monitoring might be partly different. PMID- 2096205 TI - Clinical assessment of blood pressure. AB - This study was performed to determine the blood pressure measuring techniques and accuracy of sphygmomanometers used by physicians in ambulatory care clinics on the Avalon Peninsula of Newfoundland. Of the 114 participating physicians, no physician completely followed all the recommended BP measuring techniques of the American Heart Association. Almost all physicians supported the patient's arm at heart level to measure BP. Fewer physicians used the following recommended techniques; palpation to initially assess systolic BP (38%), measurement of BP in both arms (23%), an appropriate rate of cuff deflation (18%), measurement of BP in recommended patient positions (10%), the appropriate length of rest (4%) or use of a cuff of appropriate size (3%). Approximately 8% of mercury sphygmomanometers were out of calibration by at least 4 mmHg but none were out by more than 6 mmHg. Forty percent of aneroid sphygmomanometers were out of calibration by at least 4 mmHg and of these 30% were out by 10 mmHg or more. Mercury and aneroid sphygmomanometers were used by 60% of physicians. Aneroid sphygmomanometers were used exclusively by 34% of physicians, while 5% of physicians relied solely on mercury devices. Standardized techniques for BP measurement are not used and inaccurate sphygmomanometers are common; these factors may lead to misclassification of blood pressure and inappropriate treatment of patients. PMID- 2096206 TI - The relative accuracy of simultaneous same arm, simultaneous opposite arm and sequential same arm measurements in the validation of automated blood pressure measuring devices. AB - With the increasing demand for accurate BP measuring devices there comes also the need for validation. Most validation procedures assess the accuracy of a test device against a known standard, most commonly a mercury sphygmomanometer. The best method for assessing device accuracy is to measure BP simultaneously in the same arm with the test device and a mercury sphygmomanometer. This is not always possible because the deflation mechanism of the test device interferes with the ability of an observer to auscultate the Korotkov sounds accurately. In this study a mathematical method of sequential comparison between the test device and a mercury standard in the same arm is described which is almost as accurate as simultaneous measurement in the same arm. PMID- 2096207 TI - Hypertension, creatinine, and plasma renin activity in heart transplant recipients. AB - Development of de novo hypertension in a large proportion of orthotopic heart transplant recipients receiving cyclosporine has previously been reported. This hypertension is characterized by a persistence of increased peripheral resistance, sodium retention, and loss of nocturnal decline in BP. Vascular nephropathy with plasma renin activity (PRA) elevation from cyclosporine (CsA) may also be major factor in the progress of hypertension. To investigate this hypothesis, observations of BP, creatinine (Cr), and PRA were made in 144 heart transplant recipients followed for up to four and a half years. Median Cr was 133 mumol/l. Average diastolic BP and mean PRA values were significantly higher in patients with Cr greater than or equal to the median. Cr and PRA were significantly correlated (r = 0.4; P less than 0.001) in recipients with Cr greater than or equal to 133 mumols/l but not in those with Cr less than 133 mumols/l. In a selected subsample of heart transplant recipients with repeated Cr and PRA values, Cr and PRA appeared to increase longitudinally after transplant. These data are derived from a case series of patients managed on a variety of antihypertensive agents (excluding ACE inhibitors) needed to control the persistent hypertension. PMID- 2096208 TI - A comparison of the management of hypertensive patients by nurse practitioners compared with conventional hospital care. AB - Patients with hypertension (n = 198) managed by a nurse practitioner hypertension clinic (NPC) were compared over a four-year period with an age-sex matched group of patients attending conventional hospital hypertension outpatient clinics (CHC) for follow-up in two other hospitals in the same city. Mortality is reported for an additional two years from initial presentation. There was no difference between the groups for initial supine systolic or diastolic blood pressure, weight, obesity index, alcohol use, cholesterol or glucose. The reported causes of hypertension were similar. There were more smokers initially in the CHC (46% vs. 37%). Initial drug treatment was less varied in the NPC. At the end of one year there was no significant weight loss in either group, and drug treatment was broadly similar between the two groups. Those attending the NPC, however, had a greater decrease in both supine systolic blood pressure (P less than 0.05) and diastolic blood pressure (P less than 0.01). At the end of four years there were 136 patients (69%) attending the NPC and 70 (35%) remaining in the CHC. For those remaining systolic blood pressure control was similar. Diastolic blood pressures were lower in the NPC (P less than 0.001). Mortality was not significantly different between the groups over a six-year period. This study shows that a nurse practitioner clinic can control blood pressure in a greater proportion of patients, maintain contact with more efficient follow-up of a greater percentage of patients and collect the information needed to assess the effectiveness of care over the long term. PMID- 2096209 TI - Long term follow-up of the effect of captopril on severe proteinuria in hypertensive diabetic patients. AB - We have studied the long term effects of captopril therapy on proteinuria in ten patients with non-insulin-dependent diabetes mellitus with hypertension and nephropathy. There were 7 males and 3 females, with a mean age of 53.3 +/- 10.6 years. After a run-in period of two weeks, therapy with captopril was started. The following parameters were studied: serum glucose, sodium, potassium, cholesterol and triglycerides, glycosylated haemoglobin, renal function and 24 hour urine protein excretion before and at six month intervals for up to 24 months. Average BP fell significantly from 182.5 +/- 28/95 +/- 7.1 to 146 +/- 16.7/76 +/- 18.1 mmHg although no significant changes were seen in the biochemical parameters studied, except a reduction in 24 hour urine protein excretion from 3.86 +/- 2.85 to 0.88 +/- 1.08 g/24 h after 24 months of treatment (P less than 0.01). No correlation was observed between the reduction in proteinuria and any other parameters studied. Our results confirm the reduction of proteinuria in patients with type II diabetes mellitus and stable diabetic nephropathy treated with captopril. This effect was maintained for a period of 24 months. PMID- 2096210 TI - Comparative effects of propranolol and diltiazem on systolic and diastolic left ventricular function in essential hypertension. AB - The effects of propranolol and diltiazem on left ventricular systolic and diastolic function in hypertensive subjects (DBP 90-114 mmHg) were examined with M-mode and 2D echocardiograms in 21 patients in a double-blind fashion prior to and after 4 months of treatment. Systolic function was assessed by measurement of fractional shortening, mean velocity of fibre shortening, peak systolic pressure/end systolic dimension ratio, and end systolic stress/end systolic dimension ratio. To assess diastolic function, maximal rate of change in left ventricular dimension (MAXD), maximal rate of change in posterior wall thinning (MAX PWT) and early diastolic (EDD) and late diastolic dimension changes (LDD) were calculated using digitised M-mode images of mid-wall diameter. Both propranolol and diltiazem reduced systolic and diastolic pressures similarly. No significant changes were observed in any of the parameters of systolic function with either drug. Similarly neither propranolol nor diltiazem altered MAXD or EDD significantly. Although changes in maximal rate of posterior wall thinning (MAX PWT) were not significant with either drug, diltiazem improved MAX PWT in 7 of 8 patients. The results of the study demonstrate that both propranolol and diltiazem reduce blood pressure without significant deleterious effects on systolic or diastolic function. Diastolic functional parameters, which were not abnormal at baseline, showed no consistent change with either propranolol or diltiazem. PMID- 2096211 TI - Effect of clonidine on serum inorganic phosphorus in patients with essential arterial hypertension. AB - The decrease in arterial blood pressure in patients with essential arterial hypertension treated with clonidine is associated, in 88.9% of cases, with a rise in serum inorganic phosphorus. The increase of inorganic phosphorus in the serum of patients with hypophosphataemia, during clonidine therapy, is higher (P less than 0.001) than in hypertensive patients with normal values of serum phosphorus (P less than 0.01). This effect is more significant in overweight hypertensive patients (P less than 0.0005) than in normal weight hypertensives (P less than 0.02). No correlation was noted between the rise of serum inorganic phosphorus and the decrease in systolic and diastolic arterial blood pressure. The rise of serum phosphorus concentration in hypertensive patients is attributed to inhibition of insulin release and enhancement of growth-hormone secretion induced by clonidine. PMID- 2096212 TI - Effects of nisoldipine on stress-induced changes in haemodynamics and plasma catecholamines in normotensives and hypertensives. AB - In a double-blind, placebo-controlled crossover study 10 mg nisoldipine was given orally twice daily for 3.5 days to 12 normotensives and 12 essential hypertensives. In each study period, subjects were exposed to 6 min of physical exercise and 3 min of mental stress following the morning dose on day 3 and 4, respectively. Blood pressure, heart rate, systolic time intervals (day 3 only) and plasma levels of noradrenaline, adrenaline, dopamine as well as dihydroxyphenylglycol (DOPEG; the main presynaptic metabolite of noradrenaline) were determined at rest and at the end of both tests. Nisoldipine increased resting heart rate in normotensives and hypertensives, but reduced resting BP and BP during mental stress in hypertensives only. It also increased plasma concentrations of noradrenaline and DOPEG at rest and plasma noradrenaline concentrations during mental stress in both groups. However, nisoldipine affected neither exercise- nor stress-induced changes in any of the parameters monitored here. There was a correlation between the drug-induced percentage fall in resting BP and the height of BP during placebo treatment. While the resting values of plasma DOPEG were higher in hypertensives than in normotensives, those of plasma noradrenaline were not. Consequently, the linear relationship that existed between the resting plasma concentrations of DOPEG and noradrenaline in both groups was shifted to higher DOPEG levels in hypertensives when compared with normotensives. In conclusion, the effectiveness of nisoldipine in lowering BP was the more pronounced the higher the BP to begin with. Nisoldipine did not attenuate exercise- or stress-induced increases in plasma catecholamines. Essential hypertension may be associated with an enhanced presynaptic formation of DOPEG. PMID- 2096213 TI - Pharmacokinetics of carvedilol in older and younger patients. AB - Carvedilol, a combined beta- and alpha 1-blocking drug, was given to 8 young (age 39-47) and 21 old (age 64-79) patients with essential hypertension. Clinical and pharmacokinetic responses to 12.5, 25 and 50 mg were determined and compared. In both age groups, pharmacokinetic data were similar with all three doses of carvedilol. Peak blood levels were reached within 90 minutes and at 24 hours the trough blood level was less than 10% of the peak level. Carvedilol or its metabolite did not accumulate. Falls in systolic and diastolic BP were greater than 7 mmHg in 28 of the 29 patients. The falls in diastolic BP did not differ between groups but the older group had a greater fall in systolic BP. However, the systolic BP of the older group was higher and expressed as a percentage, the falls in BP did not differ. The time to peak fall in BP was about 4 hours and was always after the time to peak blood level. There was no correlation between blood level and BP fall. When the drug was administered 24 h after the previous dose, a further fall in BP was seen indicating a greater effect at peak drug levels. Side effects were few and, during the chronic study, there was no postural hypotension or postural hypotensive symptoms. On the study days, five patients developed postural hypotension with symptoms. These were not observed at other times and may have been due to decreased sympathetic outflow on the study days. Carvedilol lowered BP in order and younger patients. There were no significant effects of age on its pharmacokinetics. Carvedilol is an effective antihypertensive agent that can be used in people with essential hypertension in all age groups. PMID- 2096214 TI - Equivalent antihypertensive effects of combination therapy using diuretic + calcium antagonist compared with diuretic + ACE inhibitor. AB - To test the hypothesis that the combination of a calcium antagonist and diuretic is less effective in lowering BP than the combination of ACE inhibitor plus diuretic, we compared two groups of patients. The first was a group of 157 consecutive patients (32% male, 90% black, aged 57 +/- 1 years) in whom the only change in therapy was the addition or deletion of either a calcium antagonist or diuretic. Each patient served as his/her own control, with a follow-up time of 41 +/- 4 days. The BP responses of this group were compared with those of another group of 170 consecutive patients (33% male, 85% black, aged 55 +/- 1 years), who had had the addition or deletion of an ACE inhibitor or diuretic some 32 +/- 2 days previously. As there were no statistically significant differences either between drugs within the classes or between the addition or deletion of a drug, the BP results were pooled. Combination therapy with calcium antagonist + diuretic was associated with a 13.4 +/- 1.7/5.4 +/- 0.9 mmHg drop in supine BP; the ACE inhibitor + diuretic combination lowered supine BP by 12.3 +/- 1.6/8.0 +/ 0.9 mmHg compared with monotherapy (all P less than 0.001 by paired t-test). The effects on standing BP were similar: calcium antagonist + diuretic, 13.2 +/- 1.9/5.6 +/- 0.9 mmHg; and ACE inhibitor + diuretic, 12.3 +/- 1.5/7.0 +/- 0.9 mmHg (all P less than 0.001). There were no significant differences in BP responses between the calcium antagonist + diuretic and ACE inhibitor + diuretic combinations. These data indicate that, regardless of the order of addition or subtraction, the combination of calcium antagonist + diuretic was more effective in lowering BP than either agent used alone, and that the combination of calcium antagonist + diuretic was as effective as the ACE inhibitor + diuretic combination. PMID- 2096215 TI - Blood pressure and liver cirrhosis. PMID- 2096216 TI - Neonatal modulation of adult rat hepatic microsomal benzo[a]pyrene hydroxylase activities by Aroclor 1254 or phenobarbital. AB - The constitutive and Aroclor 1254-induced activities of hepatic microsomal benzo[a]pyrene hydroxylases in male and female rats were determined in animals from ages 11 to 120 days. In 11-day-old noninduced male rats, benzo[a]pyrenediones and 9-hydroxybenzo[a]pyrene were the major microsomal metabolites; in 21-day-old males benzo[a]pyrene-diones and benzo[a]pyrene-9,10 dihydrodiol were predominant. In 60- and 120-day-old animals 3 hydroxybenzo[a]pyrene was the major microsomal metabolite. A similar trend was observed for the development of benzo[a]pyrene hydroxylase activities in female rats. With the exception of 4,5-dihydrodiol formation, the highest induction of individual and total benzo[a]pyrene hydroxylase activities by Aroclor 1254 was observed in the 21-day-old immature male rats, in which there was a 330- and 4.5 fold increase in the formation of 3-hydroxybenzo[a]pyrene and quinone metabolites, respectively. The induction of benzo[a]pyrene total metabolite formation by Aroclor 1254 in female rats from 11 to 120 days of age was relatively constant (i.e., 13.3- to 10.1-fold induction); however, the relative induction of the individual benzo[a]pyrene hydroxylases was highly variable. In a second set of experiments, male and female rats were neonatally exposed to phenobarbital (600 mumol/kg) or Aroclor 1254 (100 mumol/kg), and the effects of these xenobiotics on neonatal imprinting of hepatic microsomal benzo[a]pyrene hydroxylase activities were determined in the 120-day-old animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096217 TI - Differential enzyme induction of mouse liver and lung following a single low or high dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AB - The induction response of cytochrome P-450-dependent enzyme activities to a single low (5 nmol/kg) or high (50 nmol/kg, intraperitoneal [ip] dose of TCDD was examined in liver and lung homogenates over a 12-week time course in an outbred, Ah-responsive strain of mice (National Institutes of Health [NIH] Swiss). Total hepatic cytochrome P-450 was quantified, and the dealkylation of ethoxy- and benzyloxyresorufin (activities of P-450 IA1 and IIB1, respectively) were measured in both tissues at 48 and 96 hr and at 1, 4, and 12 weeks post-TCDD administration. Western immunoblotting with monoclonal antibody 1-7-1 was conducted to confirm the specific IA1-inductive effects of each dose of TCDD over the same time course. Following the low dose, specific IA1 induction was apparent in liver at the earliest time point, was maximal at 1 week, and declined to control values at 12 weeks. Pulmonary IA1 was near-maximally induced at 48 hr, and remained at that level for 4 weeks. In contrast, a tenfold higher dose of TCDD elicited similar IA1 induction profiles for both tissues, with a maximum at 1 week and a progressive loss at 4 and 12 weeks postexposure. P-450 IIB1 activity was elevated in TCDD-treated animals by enzymatic assay; however, Western immunoblotting did not confirm this finding. These data demonstrate persistent dose-dependent P450 induction over many weeks by a single TCDD dose, with significant organ-specific differences: (a) lung is more sensitive than liver to a nonmaximal inducing dose of TCDD, and (b) at a maximally inducing dose of TCDD, lung is very similar to liver in both the level and time course of IA1 induction. PMID- 2096218 TI - Oxidatively stressed lymphocytes remain in G0/G1a on mitogenic stimulation. AB - Thiol modifiers and oxidants inhibit lymphocyte activation. To investigate which of the many cell functions sensitive to oxidation are critical in this inhibition, mouse splenic lymphocytes were treated with oxidants prior to exposure to mitogen, and progression into the cell cycle was assayed. Different treatments were used to chemically dissect different potential targets within the cell: copper phenanthroline (CuP), to oxidize surface sulfhydryls; N-ethyl maleimide (NEM), to alkylate extra- and intracellular thiols; and hydrogen peroxide, which generates the highly reactive hydroxyl radical within the cell. Progression into the cell cycle was assayed with acridine orange (AO) and assays of interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) expression. The contribution of ADP-ribosylation to inhibition of mitogenesis was assessed using 3-aminobenzamide (3AB) to inhibit adenosine 5'-diphosphate (ADP)-ribose transferases. The results indicate that the CuP and NEM treatments both produce two independent inhibitory effects, that is, a failure in the production of and response to IL-2. Cells treated with these compounds were able to progress only through G1a upon mitogenic stimulation. H2O2 had more complex effects. Both ADP ribosylation and modulations of cytosolic Ca2+ were involved in the inhibitory effects. With lower inhibitory doses of H2O2, lymphocytes were completely unresponsive to mitogen and failed to exit Go upon mitogenic stimulation. If intra- and extracellular Ca2+ were buffered before treatment with H2O2, higher concentrations were required, and under these conditions cells were able to enter G1a but could not progress into G1b. Under neither of these conditions could cells produce IL-2 or express IL-2R. PMID- 2096219 TI - Diethylstilbestrol potentiates and testosterone antagonizes the action of 3 methylcholanthrene on benzo(a)pyrene metabolism in Hep G2 cells. AB - We have used the human hepatoma cell line, Hep G2, to examine the ability of hormones and xenobiotics to modulate the hepatic induction of benzo(a)pyrene hydroxylase and epoxide hydrolase. Hep G2 cells were cultured in Eagle's Minimum Essential Medium supplemented with 10% fetal calf serum. 3-Methylcholanthrene, diethylstilbestrol, testosterone propionate, and combinations of 3 methylcholanthrene, and each of the hormones were added directly to the culture media. We subsequently studied the metabolism of benzo(a)pyrene using cell lysates of the Hep G2 cells. Metabolites were quantitated by high-performance liquid chromatography (HPLC) using fluorodetection. Exposure to 3 methylcholanthrene alone resulted in an eightfold increase in total benzo(a)pyrene metabolites with a change of the predominant metabolite from the 3 hydroxybenzo(a)pyrene to the carcinogenic pathway of the benzo(a)pyrene-7,8-diol. Diethylstilbestrol and testosterone propionate resulted in small, but significant, decreases in metabolism of benzo(a)pyrene. When exposed in combination with 3-methylcholanthrene, testosterone propionate antagonized and diethylstilbestrol potentiated the metabolism of benzo(a)pyrene. 3 Methylcholanthrene, diethylstilbestrol, and combinations of 3-methylcholanthrene and diethylstilbestrol or testosterone propionate resulted in increased epoxide hydrolase activity as compared to controls. These results, carried out in a human hepatoma cell line, lend support to a concern for potentiated toxicity and carcinogenicity following exposure to complex chemical mixtures. PMID- 2096220 TI - Oxidant injury increases cell surface receptor binding of angiotensin II to pulmonary artery endothelial cells. AB - Nitrogen dioxide (NO2), an environmental oxidant, is known to activate phospholipase A1 and modulate the plasma membrane structure of porcine pulmonary artery endothelial cells. We evaluated the effects of exposure to NO2, purified phospholipase B (which acts as phospholipase A1 and A2), or phospholipase A2 on 125I-angiotensin II (Ang II) receptor binding, internalization, or both in pulmonary endothelial cells. Exposure to 5 ppm NO2 for 48 hr at 37 degrees C or 0.075 U each of phospholipase B or A2 in phosphate-buffered saline (PBS) for 30 min at 24 degrees C resulted in an increase in total Ang II binding (i.e., cell surface bound and internalized) by 45% (p less than 0.05), 50% (p less than 0.05), and 85% (p less than 0.001), respectively, compared to controls. An Ang II receptor antagonist, [Sar1 Ile8] Ang II, competitively displaced Ang II binding to control, NO2-, phospholipase B-, and phospholipase A2-exposed cells. Dissociation of bound Ang II in the presence of PBS was less than 1% of total bound Ang II in control, NO2-, and phospholipase B-exposed cells and was 50% of total bound Ang II in phospholipase A2-exposed cells. In the presence of isotonic acetic acid/NaCl, in excess of 90% of cell surface-bound Ang II was dissociated from control, NO2-, and phospholipase B-exposed cells, and there was less than 2% of Ang II detectable when acid-treated cells were subjected to NaOH solubilization. In cells exposed to phospholipase A2, acetic acid treatment did not release cell-bound Ang II, and the remaining Ang II was recovered in the NaOH solubilized fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096221 TI - Role of hypergastrinemia in the antiatrophy effect of 2,3,7,8-tetrachlorodibenzo p-dioxin on oxyntic gland mucosa of the rat stomach. AB - Atrophy of the gastrointestinal mucosa that occurs in pair-fed control rats is not observed in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats (1). Our objective was to determine if the gastrointestinal trophic hormone, gastrin, is involved in the antiatrophy effect of TCDD on the gut mucosa. Adult male Sprague Dawley rats treated with 100 micrograms/kg of TCDD were slightly hypergastrinemic 7 days after dosing and markedly hypergastrinemic 14 days after treatment whereas pair-fed control rats were normogastrinemic. After 14 days of feed restriction, atrophy of the oxyntic gland and ileum mucosa occurred in pair-fed control rats but only atrophy of the ileum mucosa developed in TCDD-treated animals. The oxyntic gland mucosa of TCDD-treated rats was protected from mucosa atrophy as well as from mucosa erosions. The protection against feed restriction-induced atrophy was demonstrated by measurements of oxyntic gland mucosal height and DNA and protein content. Since hypergastrinemia stimulates growth of oxyntic gland mucosa, but not ileum mucosa, the antiatrophy effect of TCDD on mucosa of the oxyntic gland might in part be due to hypergastrinemia. In support of this interpretation, TCDD treatment exerted an antiatrophy effect on the oxyntic gland mucosa only when TCDD-treated animals were hypergastrinemic. For example, hypergastrinemia does not develop within the first 48 hr after TCDD administration, and TCDD treatment affords no protection against fasting-induced atrophy of the oxyntic gland mucosa during this time. On the other hand, the ability of TCDD treatment to protect against feed restriction-induced erosions of the oxyntic gland mucosa might be mediated by hypergastrinemia since these events occur at a later time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096222 TI - Spectroscopic quantitation of cytochrome P-450 in human lung microsomes. AB - The cytochrome P-450 content of human lung microsomes was measured by difference spectroscopy of the carbon monoxide-complexed hemoprotein. These measurements were only possible after the microsome preparation had been subjected to centrifugation over a discontinuous sucrose gradient, to remove an opaque black contaminant. The specific concentration of total cytochrome P-450 in human lung microsomes is essentially identical to that of microsomes prepared under identical conditions from untreated baboon lungs, but is only 0.7% of the specific content found in lung microsomes from untreated rabbits. These measurements correspond well to the observed metabolic capacities of the various microsome samples. PMID- 2096223 TI - A new technique of in vitro assay of antifilarials using different life-forms of Acanthocheilonema viteae. AB - An approach has been made to develop an in vitro screening system to evaluate antifilarial efficacy of compounds and an effort has been made to establish correlation between in vivo and in vitro screening technique. The in vitro experiments were conducted simultaneously using three life-forms (adult, microfilaria and infective larva) of Acanthocheilonema viteae using five antifilarial agents representing four chemical groups. All the selected antifilarials were known to be active against one or more life-stages of human lymphatic or animal filariids. Diethylcarbamazine and Centperazine showed 100% microfilaricidal and infective larvicidal actions at concentrations of 0.5 and 0.25 mg/ml and 0.5 and 0.0313 mg/ml respectively with no effect on adult worms even at 1 mg/ml. Levamisole was effective against all the three life-stages killing 100% adult worms at 1 mg/ml, infective larvae at 0.0625 mg/ml and microfilariae at 0.0125 mg/ml, while mebendazole exhibited activity only against adult worms (100% at 0.5 mg/ml). Ivermectin killed adult females and microfilariae at 0.063 and 0.5 mg/ml respectively but did not affect infective larvae even up to 1 mg/ml concentration. The study indicated that in vitro screening system can be used for primary screening of potential antifilarial agents provided three life-forms of A. viteae are used simultaneously to avoid false negative results. It would however be more appropriate if a few compounds of a particular chemical class are initially assessed both in vivo and in vitro for validity of subsequent test results in vitro. PMID- 2096224 TI - Characterization and change of phospholipids in the aorta of Watanabe hereditable hyperlipidemic rabbit. AB - The characterization and change of lipids in aorta with the progression of atherosclerosis were elucidated in Watanabe hereditable hyperlipidemic (WHHL) rabbit, an animal model for human familial hypercholesterolemia as compared with those of normal rabbits. The amount of total phospholipids in the aorta of WHHL rabbit increased about 6-fold that of normal level. Sphingomyelin showed the largest increase and phosphatidylcholine the second in the aorta of WHHL rabbit. The fatty acid composition of sphingomyelin was characteristic of higher content of unsaturated fatty acids. It was suggested that the specific increase in both sphingomyelin and its unsaturated fatty acid content might be ascribed to regulation mechanism to recover the membrane fluidity which was reduced by the marked accumulation of cholesterol in the aorta of WHHL rabbit. Glycerophospholipids in the aorta of WHHL rabbit also contained more unsaturated fatty acids than those in normal ones. It was suggested that the higher amounts of unsaturated fatty acids of glycerophospholipids might be derived from those of serum lipoproteins and that they also might help to restore or recover membrane fluidity in the cholesterol-accumulated aorta of WHHL rabbit. Phosphatidylcholine in the aorta of WHHL rabbit contained a large amount of alkylacyl type-homologue (25-fold normal level) which was a precursor of platelet-activating factor (PAF). The increase of lysophosphatidylcholine, a potent chemotactic factor for monocyte, was also observed in WHHL rabbit. The increase of these chemical mediators indicated severe pathologic state in the atherosclerotic lesions of the aorta of WHHL rabbit. PMID- 2096225 TI - [Effects of cultural conditions on hexavalent chromium uptake and the cytotoxicity thereof in KB cell culture]. AB - To reveal the effects of cultural conditions on the cytotoxicity of hexavalent chromium, the uptake of sodium chromate (Na2CrO4) by KB cells and the colony forming efficiency of the cells were examined under various cultural conditions. The results were summarized as follows: 1) The chromium uptake by the cells after a certain period of incubation with hexavalent chromium was inhibited with the decrease of the temperature (3 degrees, 20 degrees, 37 degrees C), increase of the serum concentration (0, 10, 20, 30%) and increase of pH (6.8-8.2) of the medium. In particular, low temperatures inhibited the chromium uptake by the cells remarkably. However, in relation to the serum addition, no marked effect was found. 2) The chromium uptake by the cells increased with the volume of the medium containing an identical concentration of chromium (2 ppm) and then reached saturation when it was about 0.23 microgram per 10(6) cells. On the other hand, the chromium uptake positively correlated with the concentration of chromium and the total chromium in the medium. 3) The difference of chromium uptake by the cells in different culture media was more marked at acidic pH than that at alkaline pH. However, there was no effect of calcium chloride and glucose concentrations on the uptake of chromium. The chromium uptake by the cells in Ca Mg-free phosphate-buffered solution (PBS(-] was higher than that in other culture media. Consequently, the above results suggested that the chromium uptake by the KB cells might be affected by the various cultural conditions, especially by temperature, pH and medium volume. PMID- 2096226 TI - [The suspended particulate matter (SPM) and polycyclic aromatic hydrocarbons (PAHs) in indoor and outdoor air along a main road]. AB - The change in concentration of suspended particulate matter (SPM) in indoor and outdoor air in the Tokyo metropolitan area was studied using a new portable sampler (SPMP-sampler). The relationship between the airborne particle concentration in indoor and outdoor air varied with the aerodynamic diameters of the particles. The concentration of the SPM in indoor air increased in proportion to that in outdoor air. The polycyclic aromatic hydrocarbon (PAH) concentration in SPM also varied with the aerodynamic diameters of the particles. Fine particles with diameters of less than 2 microns contained high concentrations of PAH. The PAH concentration in indoor air increased in proportion to that in outdoor air. There were significant correlations between the concentrations of B(k)F, B(a)P, and B(ghi)P in indoor air. The mutagenic activities in the airborne particles also varied with the aerodynamic diameters of the particles. Fine particles with diameters of less than 2 microns had high mutagenic activities. PMID- 2096227 TI - [Evaluation of qualitative and quantitative tests for proteinuria and glucosuria as screening tests for cadmium-induced renal tubular dysfunction]. AB - To evaluate the screening tests for cadmium-induced renal tubular dysfunction, qualitative and quantitative tests for urinary protein and glucose have been done in 146 urine samples obtained from subjects who had lived in the cadmium-polluted Jinzu River basin in Toyama Prefecture, Japan. The subjects consisted of 66 men and 80 women aged 55 to 71 years with beta 2-microglobulinuria exceeding 1,000 micrograms/g creatinine. The results obtained from this study were as follows; 1) The positive reaction (above 1+) for protein by the dipstick method was seen in 19.7% of men and 20.0% of women, and for glucose using Tes-tape in 48.5% of men and 33.8% of women. 2) The geometric means of protein and glucose concentrations in urine were 16.4 mg/dl and 12.7 mg/dl in men, and 14.2 mg/dl and 6.8 mg/dl in women, respectively. 3) The criteria of the primary screening in the health survey system for the residents in cadmium-contaminated areas conducted by the Japan Environment Agency were a proteinuria level exceeding 10 mg/dl and a glucosuria above (+/-) with Tes-tape. Nearly all subjects with urinary beta 2 microglobulin exceeding 30 mg/g creatinine were screened by these criteria in both sexes, whereas only 52.9% of men and 30.0% of women who had urinary beta 2 microglobulin between 10 to 30 mg/g creatinine could be screened in this manner. These results indicate that semiquantitative tests are insufficient as initial tests for screening cadmium-induced renal tubular dysfunction. PMID- 2096228 TI - [Risk evaluation of stratospheric ozone depletion resulting from chlorofluorocarbons (CFC) on human health]. AB - Chlorofluorocarbon-11 (CFC11) lasts for an average of 74 years in the atmosphere, CFC12 for an average of 111 years, and CFC113 for an average of 90 years. Every CFC molecule destroys thousands of molecules of stratospheric ozone. Recently, the extent of the Antarctic ozone hole has been recognized. The depletion of stratospheric ozone may lead to increase ultraviolet-B (UV-B) radiation. UV-B radiation has many damaging effects on human health, such as snow blindness, cataract and skin cancer. UV-B radiation also suppresses the immune defenses against certain infections. While it is difficult to estimate the numerical effect on the basis of epidemiologic data in the U.S. A., UNEP and WHO estimate that for every 1% decrease in stratospheric ozone, there will be between a 0.3 to 0.6% increase in cataract. They also estimate that for every 1% depletion of ozone, the incidences of basal cell carcinoma, squamous cell carcinoma and malignant melanoma will increase 2.7, 4.6 and 0.6%, respectively. There is also concern that increased UV-B radiation might lead to an increase of the incidence and severity of infectious diseases due to suppression of the immune system. Since the data on UV-B exposure are extremely limited, it is necessary to confirm the incidence rate of skin cancer in various countries in relation to UV-B exposure. PMID- 2096229 TI - [Life styles and blood pressure: the protective effect of apple-eating habits on high blood pressure in a high-salt population]. AB - Prospective epidemiological studies of blood pressure in a high-salt population in northeastern Japan were investigated along with dietary habits such as miso soup, rice, apple, fish, milk and sake consumption as well as smoking habits. Blood pressures of the populations in 3 villages were determined once or twice a year by mass surveys from 1954, 1957 or 1958 through 1975. The means and transitions of the personal blood pressure were calculated by regression analysis of the data obtained during each entire period. The number of persons was 1127 males and 1369 females and the response rate was 98.7 percent. The average number of times of determination of blood pressure for a person was 12.9. Stepwise multiple regression analyses were run with the means and transitions of systolic and diastolic blood pressure as the dependent variables and the life styles of the population in 1958 as an independent variable based on data of persons whose blood pressures were determined 5 or more times during the entire period. According to the backward stepwise method this study confirmed the positive relationship of age and sake drinking and the negative relationship of apple eating habits to blood pressure. PMID- 2096230 TI - [Effects of sodium chloride, acetic acid and citric acid on the dissolution of aluminum from aluminum cooking utensils]. AB - In order to investigate the effects of sodium chloride and organic acids on aluminum elution from cooking utensils made of aluminum, the quantities of aluminum elution were measured in solutions with various concentrations of sodium chloride, acetic acid and citric acid by flameless atomic adsorption spectrophotometry. The increase of the aluminum elution rate from a pudding cup, an aluminum pan and an alumite pan could be clearly distinguished by the coexistence of acetic acid or citric acid and sodium chloride. The elution was low in the presence of sodium chloride at room temperature, but it was distinctly accelerated by heating. Although alumite treatment had the effect of protection against aluminum elution, such elution obviously increased, as shown by the existence of acid and sodium chloride at high temperatures. Aluminum elution rates from surface-untreated cooking utensils made of aluminum were increased by heating by a factor of several thousand. PMID- 2096232 TI - [Prophylactic effects of diets on the development of cerebrovascular lesions in stroke- prone spontaneously hypertensive rats (SHRSP)--effects of a fish-protein diet and alterations of lipoprotein metabolism]. AB - It is generally accepted that a high-protein diet prevents the development of cerebrovascular lesions and improves the survival rate in studies using stroke prone spontaneously hypertensive rats (SHRSP). Moreover, it is well documented that the preventive effect is largely due to attenuation of the development of severe hypertension. However, in addition to the reduction of blood pressure, there must be some other mechanisms which are nutritionally effective. In order to elucidate nutritionally effective mechanisms, we investigated the prophylactic effect of a protein diet (the K diet) on the development of cerebrovascular lesions in SHRSP. The diet was composed of dried bonito protein as the protein source and contained the same amount of protein as the control diet (the Funabashi SP diet). Experimental groups were maintained on the K diet from 5 (ca. 130 mmHg), 8 (ca. 200 mmHg) or 10 (ca. 230 mmHg) weeks of age and the control group was maintained on the Funabashi SP diet, with free access to the diet and to drinking water. In the experimental groups administered the K diet from 5 or 8 weeks of age, the development of hypertension was attenuated, there was a reduction of the incidence of cerebrovascular lesions and elongation of the life span was observed. On the other hand, in the experimental group administered the K diet from 10 weeks of age, a reduction of the incidence of cerebrovascular lesions and an elongation of the life-span were observed without the reduction of blood pressure. Taking the above results into account, we investigated the serum lipid metabolism, which might be affected by the administration of the K diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096231 TI - [Effects of endurance training on blood lactate, plasma noradrenaline, heart rate, and systolic blood pressure at submaximal exercise]. AB - The purpose of this study was to investigate the effects of low-intensity endurance training on the lactate threshold (LT) and the onset of blood lactate accumulation (OBLA), as well as the relationship among blood lactate, heart rate, systolic blood pressure and the plasma noradrenaline (NA) concentration during submaximal exercise before and after training. Seven middle-aged women aged 33-57 years performed endurance training on a bicycle ergometer for 60 min 3 days a week for 6 weeks at an intensity corresponding to 50% of their maximum oxygen uptake. The results were summarized as follows: 1) LT and OBLA increased significantly by 32% (p less than 0.05) and 16% (p less than 0.05), respectively, after the training. 2) The increase rate of OBLA correlated negatively to its initial level (p less than 0.05) but the increase rate of LT did not. 3) Heart rate, systolic blood pressure and the pressure rate product (systolic blood pressure x heart rate x 10(-2] at LT and OBLA did not change significantly after the training. 4) A significant linear correlation between blood lactate and NA was observed during the submaximal exercise before (p less than 0.05) and after (p less than 0.05) the training, but the slopes of the two regression lines did not differ significantly. It was concluded that low-intensity training results in a significant improvement in LT and OBLA for middle-aged women. It was further suggested that, after the training, diminished responses of the cardiovascular and sympathetic nervous system are in parallel with the decrease in the blood lactate concentration during submaximal exercise. PMID- 2096233 TI - [Development of an improved system for monitoring the peripheral circulation and its application. Part 2. Its application to the cold water immersion test in workers using vibratory tools]. AB - Using an improved system for measuring skin blood flow by the thermal clearance curve, the change of the skin blood flow in the finger (finger blood flow) of the workers using vibratory tools induced by 10 degrees C cold water immersion for 10 min was observed in order to clarify the pathogenesis of vibration-induced white finger (VWF) from the aspect of peripheral circulatory function and simultaneously to demonstrate the efficiency of the system. The subjects constituted a group of 10 workers with VWF (VWF group) and 10 healthy workers without a history of hand-arm symptoms (control group). Ages and years of exposure to vibration in the two group were almost equal. The results were as follows. 1) While the finger blood flow in the control group was remarkably decreased at 1 min after the immersion, the decrease in the VWF group was low as compared with that in the control group. This result shows that vasoconstriction just after the immersion in VWF patients is not as great as that in the control group. 2) The finger blood flow in the control group at 5 min after the immersion was increased. In contrast no increase in the VWF group was observed. These results showed that cold-induced vasodilatation (CIVD) in VWF patients diminished. 3) An increase of the finger blood flow at 1 min after stopping the immersion was observed in the VWF group. These results suggest that the property of reaction to cold in VWF patients is not excessive vasoconstriction as has been hypothesized, but the diminution of CIVD. Apart from 10 workers of VWF group, observing the change of the finger blood flow in a case in which VWF was provoked by the immersion, the author found an abnormal decrease of the finger blood flow at 5 min after the immersion. This finding supports the hypothesis that the diminution of CIVD plays an important role in VWF attack as well. Concerning the characteristics of peripheral circulatory function in VWF patients, it can therefore be considered that its reaction in VWF attack is vasospasms, while the reaction to cold is the diminution of CIVD in the non-attack phase. The cold water immersion test using the system was recognized to be useful for diagnostic examination because the estimation of finger blood flows at both measuring points, 1 min and 5 min after the immersion, could fairly well discriminate VWF patients from healthy workers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2096234 TI - An epidemiological study of tics. AB - We devised a questionnaire for estimation of each tic, and used a two-step investigation procedure, first by a parent questionnaire with 1,218 responses and second by a confirmatory telephone interview for 197 positive responses. The average estimated values were 11.3% for boys and 5.2% for girls. The prevalences were--blinking: 4.2%, head-jerking: 1.6%, shrugging: 1.2%, mouth-twitching: 0.6%, face-distortion: 0.5%, mouth-opening: 0%, throat-clearing: 2.7%, sniffing: 0.6%, and vocalization: 0.2%. According to the criteria in DSM-III-R, 5.1% of 1,218 had TTD, 2.2% had CMVTD, and 0.5% had Tourette disorder. PMID- 2096235 TI - A delusional disorder that occurred in one of a pair of monozygotic twins. AB - The authors reported a pair of male monozygotic twins in one of whom a delusional disorder occurred, and discussed the etiology of that disorder. The analysis of the twins indicates the following: 1. The disposition for the delusional disorder might be related to a psychological tendency to experience a delusion that might be based on a genetic factor. This might be strengthened by the development of a hypersensitive personality (Kretschmer, E.) promoted by environmental factors. 2. A hypersensitive personality might be a significant risk factor for the delusional disorder. PMID- 2096236 TI - Psychogeriatric patients in a general hospital: role of geropsychiatric consultation. AB - A total of 505 elderly patients aged 65 and over, seen at the Department of Psychiatry of Tosei General Hospital, were investigated retrospectively and classified according to the DSM-III-R criteria. The increase in the number of psychogeriatric patients over the last two decades was statistically significant. Organic mental disorders were most frequent (51%), followed by mood disorders (22%), sleep disorders (7%), somatoform disorders (6%), anxiety disorders (5%) and others. A high referral rate (42%) and a high incidence of various concurrent physical disorders (52%) were observed, and the role of geropsychiatric consultation in a general hospital was evaluated and discussed. PMID- 2096237 TI - Psychiatric patients showing irregular beta activities in EEGs and treatment with antiepileptic drugs: a report of 15 cases. AB - Fifteen psychiatric cases are reported who were clinically diagnosed as schizophrenic, affective disorders, or neurotic, but resisted standard medication regimens, all showing irregular beta activities on EEGs. The cases tended to display symptoms in common, such as dysphoria, emotional instability or frequent physical complaints. These characteristic symptoms share something mutually with the symptoms shown in some epileptic patients or psychiatric patients with epileptic EEG abnormalities without clinical seizures. Antiepileptic drugs seemed more specifically effective to the above symptoms. More than half of these cases showed improvement on EEG findings such as a decrease in irregular beta activities and an increase in rhythmicity or regularity of alpha activities along with clinical improvement with the administration of adjunctive antiepileptic drugs. These results suggest that the adjunctive administration of antiepileptic drugs to patients with irregular beta activities on EEGs is clinically useful and an EEG examination has much value in psychiatric practice to find the criteria of drug therapy. PMID- 2096238 TI - REM sleep without muscle atonia (stage 1-REM) and its relation to delirious behavior during sleep in patients with degenerative diseases involving the brain stem. AB - Nocturnal sleep was examined in 12 patients with degenerative diseases involving the brain stem and in 2 patients with late cerebellar cortical atrophy (LCCA). A peculiar sleep state, characterized by the concomitant appearance of a low voltage mixed frequency EEG, rapid eye movements (REMs) and tonic EMG in mental muscles, repeatedly appeared during nocturnal sleep in all of the 12 patients with degenerative diseases involving the brain stem and it was called stage 1-REM after Tachibana et al. In 8 of the 12 patients, delirious or oneiric behavior appeared during, or soon after, the episodes of stage 1-REM. Inner experiences reported by one of the subjects well corresponded to his behavior during the episode of stage 1-REM. Stage 1-REM was not observed during nocturnal sleep of the patients with LCCA. These results indicate that a degenerative lesion in the brain stem induced stage 1-REM and delirious behavior during nocturnal sleep through abolishing muscle atonia of REM sleep and causing dissociation of the functional components characterizing REM sleep. PMID- 2096239 TI - Enlargement of the anterior horn of the lateral ventricle in schizophrenic patients: chronological and morphometrical studies. AB - The anterior horn and lateral ventricular sizes of the brain CT were selected for measurement and comparison between 47 schizophrenic patients and 48 neurotic cases, which constituted the control subjects. The ventricular brain ratio (VBR) and the linear ratio (LR 1-6) in multiple age groups were calculated, analyzed and compared using the Student's t test, the two-way ANOVA and Bonferroni's methods. It was found that the VBR of the anterior horn and modified bicaudate cerebroventricular index of the teenage schizophrenics were significantly greater than those of the teenage controls (p less than 0.01) and the ventricular sizes were not associated with the different stages of age except for the cases of the teenage group. These results support the hypothesis of previous investigators that the ventricular enlargement is present early in the course of schizophrenia and provide additional evidence that in teenage schizophrenic patients there is a tendency of the enlargement of the anterior horn of the lateral ventricle which may be related with a morphological vulnerability in the prefrontal cortex. PMID- 2096240 TI - Three cases of chronic subdural hematoma with depressive state. AB - The authors described 3 cases of chronic subdural hematoma (CSDH) with a depressive state. There were no abnormal findings from general and neurological examinations. Computed tomographic (CT) brain scans revealed sickle-shaped low density areas in the bilateral frontal lobes. Two of the 3 cases had not had episodes of head contusion, and it was not until the CT brain scanning that they were found to have CSDH. Evacuation of the hematomas was not considered suitable and the depressive state of these 2 cases was improved by antidepressants. The remaining case seemed to have become depressive because of failure in business. After the head contusion, his depressive state gradually became more severe. A neurosurgical operation was carried out to evacuate the hematoma. CSDH seemed to aggravate his depressive state. These 3 cases show that CSDH located in the bilateral frontal lobes may cause and/or influence affective disorder. PMID- 2096241 TI - Influence of indeloxazine hydrochloride upon photic driving responses elicited by flickering dot pattern and red flicker stimuli in elderly patients. AB - We studied the influence of indeloxazine hydrochloride (IH) upon photic driving responses (PDRs) elicited by a 5 Hz flickering dot pattern and red flicker stimuli. Comparisons were made from a total of 22 elderly patients. By oral IH administration, clinical improvement was found in 12 patients with cerebral arteriosclerosis (improved group), whereas it was not observed in 6 patients with cerebral arteriosclerosis, 2 patients with multiinfarct dementia and 2 patients with Alzheimer's disease (unimproved group). Before and after the IH administration, an EEG examination by the above visual stimuli was carried out in each patient; a power spectral analysis of the occipital PDRs elicited by the visual stimuli was then made. The powers of PDRs elicited by the flickering dot pattern stimulation were not significantly different in both groups; those of 10 and 15 Hz PDRs elicited by the red flicker stimulation, however, decreased significantly by the IH administration in the improved group. It was suggested that such an analysis of PDRs elicited by the red flicker stimulation might perhaps be useful as one of the indicators to evaluate the efficacy of IH. PMID- 2096242 TI - Auditory brain stem response (ABR) in eating disorder. AB - Auditory brain stem responses were recorded in 10 eating disorder patients and 10 normal control subjects. Absolute latencies, interwave latencies, absolute amplitudes, and amplitude ratios were investigated. A nonsignificant difference was found between the eating disorder group and the normal control group as far as the absolute latencies and interwave latencies were concerned. But the eating disorder patients had significantly smaller amplitude ratios (III/I, IV-V/I) and absolute amplitude (V) than did the control subjects. These findings suggest that some dysfunction exists in the region of brain stem. It may be related with the pathophysiology in patients with eating disorder. PMID- 2096243 TI - Carmofur-induced organic mental disorders. AB - Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe. PMID- 2096244 TI - Electroencephalographic changes during and after water intoxication. AB - A case of water intoxication with remarkable hyponatremia was investigated with a special reference to EEG changes during and after the episode. The patient recovered his EEG as his consciousness disturbance had improved through an intravenous infusion of high osmolality saline, correlating with the serum sodium level. Further, the clinical importance of recording EEG for water intoxication was stressed. PMID- 2096245 TI - Chronic herpes simplex encephalitis with somnambulism: CT, MR and SPECT findings. AB - A 64-year-old male with herpes simplex encephalitis had shown somnambulism and memory disturbance for nine months before consciousness disturbance appeared. Brain CT, MR and SPECT revealed lesions in the right temporal lobe. The atypical clinical course of this patient, including chronicity and focal symptom, is discussed. PMID- 2096246 TI - The complex episode of transient global amnesia. AB - In most reports, Transient Global Amnesia (TGA) consisted of a single episode of total amnesia. The detailed investigation on the process of recovery from amnesia in the present two cases of TGA indicated the existence of a complex episode of TGA which consisted of a sequence of episodes of total amnesia. PMID- 2096247 TI - [Effect of resuming work after myocardial infarction on its recurrence and mortality in long-term observations]. AB - 60 to 95% pts in the age group below 60 return to work after having* suffered the first M.I. Up to the present moment, it has not been proved whether such return influences in any (positive or negative) way the recurrence of M.I. or the mortality rate. Two groups of pts who underwent M.I. in the years 1976-84 were included in the long term questionnaire observation: 1. 222 men (mean age 49.3 +/ 3.8 yrs) who resumed work and; 2. 153 men (mean age 50.7 +/- 8.4 yrs) who did not return to work after the first M.I. All pts were sent the questionnaires by post annually. The aim of the questionnaire was to establish whether the patient is alive, if he underwent reinfarction and, in case of death--what was its cause. Until 1985 reinfarction occurred in 25%, and until 1989--in 33% of the pts who resumed work, and 42% of pts who did not. The mean value of reinfarction was about 1.4 in the first group and 1.5 in the latter. Until 1985 the death rate was respectively 15% and 12%. Until 1989--the death rate was 28% and 30%. Thus, the differences between those two groups were statistically insignificant. In conclusion, it may--indirectly--speak in favour of resuming work after the first M.I., showing that, although it does not decrease the reinfarction and mortality rates, it also does not increase the risk. PMID- 2096248 TI - [Sinoatrial node in primary mitral valve prolapse (electrophysiological study)]. AB - 40 patients with MVP (mean age 36 years--group I) and 20 controls without any heart disease (mean age 40 years--group II) after thorough clinical examination (including Holter monitoring) were subjected to electrophysiological study for sinoatrial node function assessment. The following parameters were studied (before and after "pharmacological denervation"):, SNRT, CSNRT, SP and SACT (using direct method and Strauss and Narul's method). SN dysfunction was found in 19 patients with MVP (37.5%) and in 3 controls (15%) in 24-hour Holter ecg. In the electrophysiological study SN dysfunction was diagnosed in 13 patients (32.5%) of group I. 10 of them displayed also electrocardiographic symptoms of SN dysfunction. "Pharmacological denervation" of the heart (propranolol 0.1 mg/kg, atropine 0.02 mg/kg) revealed 4 cases of concealed SN dysfunction defining the functional background of abnormalities in 7 out of 13 patients. Our data show that SN dysfunction is common in patients with MVP. Electrophysiological study performed with "pharmacological denervation" may disclose cases of concealed SN dysfunction and define them as functional or organic. PMID- 2096250 TI - [Usefulness of determining creatine kinase BB isoenzyme activity in early diagnosis of myocardial infarction]. AB - The value of radioimmunoassay for creatine kinase BB isoenzyme (CK-BB) determination in early diagnosis of acute myocardial infarction was estimated. The clinical material consisted of 35 randomly selected patients admitted to a coronary care unit during the 4 h after chest pain suspected for myocardial infarction. In all patients standard 12 lead electrocardiograms were obtained on admission and at 24, 48 and 72 hours after admission. Blood samples for CK-BB analysis were collected on admission and at 4 hourly intervals for 48 h after admission. Aspartate aminotransferase (GOT) activity was determined in all patients on admission and in samples obtained at 24 and 48 hours. The patients were classified to 3 groups according to electrocardiographic and clinical findings. The first group consisted of 10 patients whose electrocardiograms fulfilled the criteria of transmural infarction. The electrocardiograms of 10 patients of the second group fulfilled the criteria of subendocardial infarction. The remaining 15 patients made up a third group of coronary insufficiency. The activity of CK-BB at various time intervals after chest pain in all groups was compared in order to estimate the value of this method for differentiation of the 3 causes of coronary pain. The frequency of positive results (the values exceeding upper limits of normal range for healthy people) at various time intervals after pain obtained with both enzymatic methods was compared in order to estimate the sensitivity of analysed method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096249 TI - [Comparison of the course of myocardial infarction and post-infarction morbidity among urban and rural populations in the Kielce region]. AB - An analysis is made of the course of myocardial infarct and the post-hospital period of the illness in 997 patients from the Kielce Region who were hospitalized in the Clinical Department of Cardiology in the years 1977-1985. The patients were classified into three groups: I--a group of 226 patients who have resided in town since birth, II--a group of 507 patients who resided in the rural areas till the age 14-18 years and who later moved to towns, and III--a group of 264 patients who have lived in rural areas since birth. All the three groups were comparable with one another with respect to the proportion of hospitalized men and women, the average age of hospitalized men and women, frequency of occurrence of supraventricular and ventricular arrhythmias in the course of the hospital phase of illness, hospital death rate up to the age of 70 years, an increased proportion of hospital death rate of women in relation to that of men and the structures of causes of death during the hospital period of illness. The main differences concerned: a markedly lower hospital death rate in the group of rural population over the age of 70 (p less than 0.001), a markedly more frequent occurrence of the risk factors of ischaemic heart disease in the group of urban population, and a markedly more frequent occurrence of block A-V IIIo and the arrhythmia disturbances of intraventricular conduction in the group of rural population. Hospital death rate in the analyzed period was 19.2%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096251 TI - [Unusual location of mural thrombi in the right atrium caused by pathological changes in the sinoatrial node]. AB - We present a post-mortem examination of two hearts in which we found organized mural thrombi attached to the right atrial endocardium in the recess called antrum atrii dextri. This region is a place where the sinus node is situated very close to the endocardium of right atrium. Any pathological process involving the node (inflammation, degeneration) may reach this part of endocardium by continuity, this in turn creates convenient conditions for mural thrombi formation. The first case--a 52-year old man who died of severe congestive heart failure caused by rheumatic disease with mitral and aortic stenosis. Atrial fibrillation had developed several years before his death. Apart from typical changes of mitral and aortic valves a post-mortem examination revealed an organized, globular thrombus in antrum atrii dextri. In the microscopical findings of the sino-atrial region the fatty degeneration of the sinus node with multiple mononuclear cell infiltration was the most striking feature. The sinus node artery was narrowed due to fibro-muscular dysplasia of its wall. The second case--a 74-years old man who suffered from arterial hypertension and chronic pyelonephritis with a history of heart infarct in the past. The ECG recording showed multifocal atrial rythm with variable P wave morphology and P-Q distance. At necropsy the whole heart was significantly enlarged with no scars or any other signs of healed infarct. The microscopical findings revealed the heart muscle to be infiltrated by amyloid deposits particularly apparent in the sinus node. Similar thrombus of 1.5 cm in diameter was found in antrum of the right atrium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096252 TI - [Effect of coronary disease risk factors on the progression of coronary arteriosclerosis]. AB - A group of 43 patients (pts) from a larger group 451 pts with coronary artery disease (CAD) confirmed by coronary angiography were recatheterized because of deterioration of symptoms. After the first angiography patients had no indications to coronary artery bypass grafting (CABG) or gave no consent to surgery. The group comprised 3 women and 40 men aged 27 to 62 years (mean age 45 +/- 8 years). The mean interval between coronarography was 35 +/- 22 months. Four independent reviewers evaluated 15 segments of coronary arteries according to American Heart Association. The coronary lesions were scored on the basis of reduction in luminal diameter as follows: 0 point = 0-29%, 1 = 30-49%, 2 = 50 69%, 3 = 70-98%, 4 = 90-99%, 5 = 100% occlusion. The influence of the following risk factors on the progression was evaluated: age, sex, hypertension, diabetes, lipid disturbances, smoking, hyperuricaemia, family history. The patients were divided into 3 groups: group I--no or slight progression (0 to 4 points) in two successive coronary angiographies, group II--moderate progression (5 to 9 points) and group II--significant progression (10 points or more). The number of patients in these groups was 14, 12 and 17 respectively. In such isolated groups, the clinical events were compared: unstable angina, myocardial infarctions, need for CABG, cardiac deaths within follow-up period. The ejection fraction of the left ventricle was also evaluated. STATISTICAL ANALYSIS: was conducted by multiple regression model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096253 TI - [Cor triatriatum dextrum: a subsequent anatomic form]. PMID- 2096254 TI - [Mitral valve prolapse--a mysterious clinical syndrome]. PMID- 2096255 TI - [Blood viscosity and myocardial microcirculation]. PMID- 2096256 TI - [Hemochromatosis of the heart]. PMID- 2096257 TI - Isolation of Staphylococcus hyicus subsp. hyicus from pigs affected with exudative epidermitis and experimental infection of piglets with isolates. AB - Five strains of Staphylococcus hyicus subsp. hyicus were isolated: three strains (P-1, P-2 and P-3) from the crust on the body surface of 6-month-old pigs on a farm in Aomori prefecture, and two (P-5 and P-6) from both the crust on the body surface and the joint of a 1-month-old piglet with exudative epidermitis (EE) on another farm. The characterization of the isolates and the experimental infection of the piglets with strain P-1 were carried out. Subcutaneous inoculation with the bacterial suspension (10(10) CFU) produced EE to all nine piglets. Eight of them had exudation and exfoliation within 24 hr of infection. Histopathologically, disappearance of stratum corneum and necrosis with vacuolar degeneration of prickle cells were remarkable in the epidermis. Infiltration of neutrophils and lymphocytes were observed in the dermis. The results clearly indicate that S. hyicus is responsible for incrustation of the body surface of weanling pigs and exudative epidermitis in young piglets. PMID- 2096258 TI - Drug resistance plasmids of Actinobacillus (Haemophilus) pleuropneumoniae serotype 2 strains isolated from swine. AB - Drug resistance plasmids were detected in two drug resistant strains of Actinobacillus (Haemophilus) pleuropneumoniae serotype 2 isolated in Japan. One strain, Hpn25, was resistant to ampicillin, kanamycin, streptomycin and sulfonamides, and harbored two plasmids with a molecular size of 3.7 and 4.1 kilobases (kb). The other strain, Hpn18, which was resistant to streptomycin, tetracycline, and chloramphenicol, harbored three plasmids with a molecular size of 2.2, 12, and 35 kb. The resistance of Hpn 25 to streptomycin and sulfonamides is mediated by a 4.1 kb plasmid and that of Hpn 18 to streptomycin and chloramphenicol by one or more of the 2.2, 12, and 35 kb plasmids. PMID- 2096259 TI - The epithelial neoplasm observed in the cultured coho salmon, Oncorhynchus kisutch. AB - The epithelial neoplasms were observed on the mouth of the cultured coho salmon, Oncorhynchus kisutch. Histopathologically, the tumors were formed to be proliferative epithelial cells, but no change was observed in other organs. The virus from this tumor was isolated in RTG-2 and CHSE-214 cells and developed the cytopathic effect which characterized to be the formation of syncytia and the migration of chromatin. This virus was neutralized with anti-Oncorhynchus masou virus (OMV) rabbit serum. PMID- 2096260 TI - Dr. Toju Hata and Dr. Satoshi Omura received the Japan Academy Award. PMID- 2096261 TI - [Density distribution and direction of bending strength in cross- sections of the tibial head in humans]. PMID- 2096262 TI - Possible binding proteins of ras p21 in human erythrocyte membrane. AB - The direct binding protein(s) of ras p21 was investigated in the inside-out vesicles of human erythrocyte ghosts using the pure v-Kirsten (Ki)-ras p21 synthesized in E. coli. The bound ras p21 was detected immunochemically using an anti-v-Ki-ras p21 monoclonal antibody. ras p21 was overlaid on the vesicle proteins immobilized on a nitrocellulose sheet transferred from the gel of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. ras p21 bound to bands 4.2 and 6. ras p21-binding to bands 4.2 and 6 was reduced by prior incubation of ras p21 with the purified band 4.2 or 6 protein. Furthermore, when ras p21 was mixed with inside-out vesicles and then centrifuged, ras p21 was coprecipitated with the vesicles. Prior digestion of the vesicles with trypsin reduced this binding significantly. These results indicate that v-Ki-ras p21 can bind directly to bands 4.2 and 6 of human erythrocyte membranes as fat as tested in an in vitro cell-free system. PMID- 2096263 TI - Differential regulation of protein kinase C subspecies in human promyelocytic leukemia cell line HL-60 during differentiation induced by retinoic acid. AB - Protein kinase C (PKC) is a multifunctional protein-Ser/Thr kinase and is generally accepted to be involved in a wide variety of cellular signal transduction. Recent biochemical fractionation of PKC as well as sequence analysis of its cDNA clone has revealed the existence of multiple subspecies of this enzyme with obvious tissue- and cell-specific expression. The present study is concerned with the differential regulation of expression of PKC subspecies of human promyelocytic leukemia cell line HL-60 during differentiation toward granulocyte-like cells induced by retinoic acid. PKC in HL-60 cells is resolved into three distinct subspecies (peak a, b, and c) by the hydroxyapatite column chromatography. Biochemical and immunochemical analyses revealed that peak a and c enzymes were identified with the type II (beta II) and type III (alpha) PKC subspecies previously identified and characterized from brain. On the other hand, peak b enzyme was separable from type I, II and III PKC, and is suggested to be unidentified PKC subspecies possessing subtly different characters from others. Treatment of HL-60 cells with 1 microM retinoic acid caused the decrease in peak b activity within 24 h, while peak a activity was increased and peak c activity was slightly decreased within 48 h. The elution profile of PKC subspecies in human peripheral neutrophils resembled that obtained with HL-60 cells treated with RA. The results imply that activities of PKC subspecies in HL-60 cells may be distinctly regulated by retinoic acid treatment prior to the achievement of cell differentiation. PMID- 2096264 TI - [Major depression and "deterioration" of intellectual function]. AB - Forty five subjects with major depression or bipolar disorder were studied during the symptom-free period using the Wechsler and Rorschach tests. The tests revealed a reduced capacity to utilise data obtained by analysis and to integrate them by the organisation of complex thought processes as well as frequent loss of contact with reality. This finding seems to demonstrate that the apparently symptom-free periods of depression often display alterations in the capacity for thought. PMID- 2096265 TI - [Use of DSM-III R and other psychometric tests in consultation psychiatry. Consideration of 85 patients]. AB - DSM-III R diagnostic categories were used in 85 consecutive patients attending consultation at the Liaison Psychiatry Service of Padua University School of Medicine. The aim was to render the diagnosis as objective as possible. The same patients were asked to fill in three well-known self-rating scales (Eysenck Personality Inventory, Illness Behaviour Questionnaire, Symptom Rating Test) and the scores obtained were correlated with the diagnostic categories. In the Authors' opinion, the use of diagnostic instruments in the traditional psychiatric setting of the consultation allows a marked improvement in the understanding of the content of the prescription written by the referring physician. DSM-III R is an instrument which meets such requirements. The same cannot be said of the rating scales used, which were found less useful. PMID- 2096266 TI - [Psychopathological characteristics of psychiatric disturbances in the elderly]. AB - A series of studies have focused on the problem of identifying and defining the specific characteristics of senile psychiatric pathology with greater precision. The aim of the present study was to examine symptomatological aspects of a group of psychiatric patients divided into different age ranges. The possible presence of psychopathologically defined (e.g. phobia, obsession, convulsive symptoms, hallucinations, deliria) and more aspecific symptoms (e.g. those which are generically involutive, confusion, anxiety, depression, insomnia, suicide attempts) was assessed in a group of 2018 psychiatric out-patients. It was found that senile psychiatric pathology presents a symptomatology which is generally aspecific and not clearly defined, and that there are peculiarities which differentiate it from that in the adult. PMID- 2096267 TI - [Social adjustment and psychiatric re-admission: a study using a self-rating scale]. AB - The paper describes the results of a study on the relationship between the degree of social adjustment and re-admission of discharged psychiatric patients using the Italian version of the SAG (Self Assessment Guide). The validity of such a scale has been described in previous works. In this study, the test-retest assessment has proved the reliability of the scale. The test was administered to a sample of 51 patients during the first week of hospitalization, 26 of whom were followed up three months after discharge. A statistically significant improvement was observed, on the SAG score obtained during the follow-up, in patients (n = 16) who were not admitted to hospital in the 12 month period following discharge. This was unlike the case of those who required a new admission. The improvement concerned mainly the total score, the affectivity, the interpersonal functioning and aggressivity scales. PMID- 2096268 TI - [Learning disturbances in developmental ages. Consideration of some clinical cases studied with a neuropsychiatric approach]. AB - The psychoanalytic and neuropsychiatric literature on learning disturbances has been reviewed. Relations between learning disturbances, psycho-affective, cognitive and neurological development are examined. Particular attention is paid to Klein's theory of intellectual inhibition and the integrative approach described by Rothstein. Four clinical cases, which seem to exemplify the infantile neuropsychiatric integrative approach are then presented. Finally, stress is laid on the pathogenetic interrelations between psychopathological and organic aspects of the children considered and the similarities between learning disturbances and pseudo mental deficiency. PMID- 2096271 TI - [The "myth", psychopathological component and variant]. AB - With reference to their years of experience in psychiatric work, pre- and post Law 180, in various institutional contexts and sociocultural situations, the "myth" element (term counter-posed to "logos") is considered to be an important psychopathological component, above all in an anthropological reflexion on the major teachings of the European psychopathological school. Nevertheless, in the current phase of cultural massification, this component seems to dissolve, and today there is a prevalence of a psychopathological phenomenology dominated by elements of negative type (autism, inhibition, depression). PMID- 2096269 TI - [Problems in training operatives in mental health service ]. AB - The Author talks about psychiatric training and the difficulties it can provoke in students and teachers. He underlines the importance of the psychiatrist patient relationship and the importance to hearing and listening without judging; he also points out that too often the attitude toward psychiatric patients is too "medicalistic". An institutional, structural and cultural change is needed to be able to really modify things. PMID- 2096270 TI - [Protection and risk factors with respect to "burnout" of operatives. A comparative study of the psychosocial centers of Milan and Trieste]. AB - The Maslach Burn Out Inventory (1981) has been applied to a group of workers at three Psychosocial Centres at Milan and Trieste characterised by differing work styles. Point scores were related to a number of variables relative to the professional situation and work organisation. The same scores were related to the results of a questionnaire (Contessa 1987) on the operator's perception of his activity and on motivational factors with respect to the professional choice in actuality and at the beginning of the career. It was therefore possible to identify a set of positive correlations that indicate the presence of factors which increase or reduce B.O. Level. PMID- 2096272 TI - [Depression and environmental, cultural and psychosocial variables in aging: "the delusions and sweet sadness of the elderly"]. AB - The need to distinguish, in the elderly, a condition that is strictly and exclusively psychological characterised by an attitude of "sweet sadness" from a frankly pathological situation typical of the clinical picture of depression is underlined. PMID- 2096273 TI - [Psychology and psychopathology of women undergoing voluntary abortion]. AB - When facing the abortion question the following are necessary: more complete information on the consequences of indiscriminate sexual relations; a wider spread knowledge of contraceptive practices; the institution of special aid to unmarried mothers so as to prevent abortion remaining the only possible solution for an unbearable situation and which hides a serious psychological risk. PMID- 2096274 TI - The immune system in inflammatory bowel disease. PMID- 2096275 TI - The role of the epithelial cell in immunoregulation: pathogenetic and therapeutic implications. PMID- 2096276 TI - Antimetabolites in inflammatory bowel disease: long-term experience. PMID- 2096277 TI - Immunomodulation in rheumatic and related diseases. PMID- 2096278 TI - Worldwide experience with Sandimmune (cyclosporine) in autoimmune diseases: multiple sclerosis, rheumatoid arthritis, psoriasis. PMID- 2096279 TI - Cyclosporine therapy in inflammatory bowel disease: open-label experience. PMID- 2096281 TI - Assessing therapeutic efficacy: how well does anything work? PMID- 2096280 TI - Cyclosporine and the kidney: lessons for the gastroenterologist. PMID- 2096282 TI - Drugs and violence: causes, correlates, and consequences. PMID- 2096283 TI - Introduction: exploring the substance abuse-violence connection. PMID- 2096286 TI - Gangs, drugs, and violence. PMID- 2096284 TI - The relationship between cocaine use, drug sales, and other delinquency among a cohort of high-risk youths over time. PMID- 2096287 TI - The interrelationships between alcohol and drugs and family violence. PMID- 2096285 TI - The drug use-violent delinquency link among adolescent Mexican-Americans. PMID- 2096288 TI - Drug-related violence and street prostitution. PMID- 2096289 TI - Drug disorder, mental illness, and violence. PMID- 2096290 TI - Who's right: different outcomes when police and scientists view the same set of homicide events, New York City, 1988. PMID- 2096291 TI - Summary thoughts about drugs and violence. PMID- 2096292 TI - Violence associated with acute cocaine use in patients admitted to a medical emergency department. PMID- 2096293 TI - The operational styles of crack houses in Detroit. AB - This chapter identified three methods by which crack cocaine is distributed at the retail level: the street-corner or walk-up sales system, the runners and beepermen system, and the crack house. The chapter devoted primary attention to the crack house, because it appears as the most popular method for distribution. In examining the crack house, it is noted that there are identifiable styles of crack-house operations. If the quality and quantity of social interaction, as well as the situation in which sellers posture themselves, are taken as indices, then a typology can be created characterizing crack-house operations. One end of the scale is an austere method in which social interaction between buyer and seller is severely restricted; on the other, crack houses operate as tavern-style exchange locations, which include socialization above and beyond that required for the exchange of money for crack. The nature of these exchanges are themselves important, since they involve social behaviors that are of concern. One concern is the degree and nature of violence as it is associated with drug abuse. The data in this chapter describe some ways in which violence appears within the crack subculture. This violence comes from multiple sources, but some prominent ones appear to be the businesslike operations of crack distribution, the personal disorganization that surrounds and characterizes the crack-consuming environment, and the distortions of character that crack users describe as often accompanying significant binges of crack consumption. Distributors use violence to control situations. Violence is most prominently used for security at the point of retail sale, to periodically resolve conflicts with rivals, and to discipline employees when necessary. Insofar as it is described by this group of informants, crack as a social phenomenon is tied to violent and abusive behavior. This chapter reports on behaviors that, although not traditionally violent, are of concern and bear upon public health and safety. Tavern-style crack houses may encourage and make possible hypersexuality among participants and thus increase STD and HIV risks. The use of barter as a supplement to a cash economy in the crack trade represents further complications in creating social policies in reaction to this behavior. A range of other illegal and problematic behaviors was also described, illustrating the complexity of interactions that constitute the life of street-level crack users. The social policies that may be called for in response to these social events are not simple and are most certainly not defined by these particular data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2096294 TI - Violence as regulation and social control in the distribution of crack. PMID- 2096295 TI - The crack-violence connection within a population of hard-core adolescent offenders. PMID- 2096296 TI - Determination of muscarinic agonist potencies at M1 and M2 muscarinic receptors in a modified pithed rat preparation. AB - The agonistic potencies of (+/-)muscarine, (+/-)cis-2-methyl-5- [(dimethylamino)methyl]-1,3-oxathiolane methiodide (cis-oxathiolane) and its two enantiomers were determined at muscarinic M1 and M2 receptors in the pithed rat. In non-pretreated animals, i.v. administration of these agents produced bradycardic effects mediated by cardiac M2 receptors followed by increases in heart rate mediated by M1 receptors in sympathetic ganglia. As these responses have been shown to partly overlap, "true" M1 and M2 potencies were determined after selective blockade of M1 and M2 receptors by pirenzepine and methoctramine, respectively. A similar rank order of agonist potencies was obtained at M1 and M2 receptors: (+)cis-oxathiolane greater than (+/-)cis-oxathiolane greater than (+/ )muscarine greater than (-)cis-oxathiolane. At both receptor subtypes, (+)cis oxathiolane was considerably more potent (ca. 30-fold) than its corresponding (-) enantiomer indicating that the agonist binding sites of the two receptor subtypes may have similar stereochemical properties. While (+/-)muscarine showed similar potencies at M1 and M2 receptors, racemic cis-oxathiolane and its two enantiomers showed a slight selectivity (3-7 fold) for M1 receptors indicating the potential usefulness of these compounds in the development of selective M1 receptor agonists. PMID- 2096297 TI - Cocaine effects in the ventral tegmental area: evidence for an indirect dopaminergic mechanism of action. AB - Behavioral studies have implicated central dopaminergic systems, especially the ventral tegmental area of Tsai (VTA), in the mediation of the reinforcing effects of drugs of abuse such as cocaine. A brain slice preparation of the VTA was used to assess the direct effects of cocaine on the spontaneous activity of dopamine type neurons. When superfused with 1-10 microM cocaine the firing rate of spontaneously active VTA neurons was decreased, with no corresponding change in spike height. While there was a considerable variability in the response to a given concentration of cocaine among the individual units, every cell inhibited by dopamine was also inhibited by cocaine. The local anesthetic lidocaine had variable effects on firing rate, but never potentiated the inhibitory effects of dopamine. Inhibitory responses to either dopamine or cocaine were blocked by the specific D2 dopamine receptor antagonist sulpiride. Small concentrations of cocaine (0.1-0.5 microM), which by themselves had little or no effect on spontaneous activity, potentiated the inhibitory effect of exogenously applied dopamine. Furthermore, the inhibitory action of apomorphine on spontaneous activity in the VTA was not potentiated by cocaine. These observations suggest that in low concentrations, cocaine can act as a dopamine reuptake inhibitor in the VTA, and that the resultant increase in extracellular dopamine acts upon dopamine autoreceptors to inhibit cellular activity. PMID- 2096298 TI - Involvement of capsaicin-sensitive neurones in hyperalgesia and enhanced opioid antinociception in inflammation. AB - The effects of capsaicin pretreatment of adult rats was investigated on consequences of unilateral paw inflammation induced by inoculation with Freund's adjuvant. Decrease in mechanical nociceptive threshold in the inflamed paw, as measured by the paw pressure test, was dose-dependently inhibited by capsaicin (20-150 mg/kg s.c.). In control rats, the antinociceptive action of morphine (0.8 1.9 mg/kg s.c.) was greater in the inflamed than in the non-inflamed paw; this difference was absent in capsaicin-treated animals. Increased volume or skin temperature of the inflamed paw was not influenced by capsaicin. It is concluded that capsaicin-sensitive, presumably C-fibre neurones, but not an alteration of the inflammation itself by capsaicin, mediate hyperalgesia and increased morphine antinociception in the rat paw with adjuvant-induced inflammation. PMID- 2096299 TI - Desensitization of capsaicin-evoked neuropeptide release--influence of Ca2+ and temperature. AB - Capsaicin-induced stimulation and desensitization of neuropeptide release from primary afferent neurons was investigated in the rat urinary bladder in-vitro. The capsaicin (5 min contact time)-evoked release of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) was dose-dependent; threshold to produce detectable release was 0.1 mumol/l, the EC50 was 0.17 mumol/l. Pre-exposure of tissues to capsaicin (0.1-1.0 mumol/l, 5 min contact time) caused a dose dependent reduction of the amount of CGRP-IR which was released by a second exposure to capsaicin. At 0.1 and 0.3 mumol/l, capsaicin was less effective to inhibit the subsequent K(+)-evoked release than that evoked by a second capsaicin exposure. Pre-exposure to 1 mumol/l capsaicin completely prevented subsequent K(+)- or capsaicin-evoked release of CGRP-IR. Exposure of the preparation to capsaicin (0.3 mumol/l) in a Ca2(+)-free, EDTA-containing medium did not produce release of CGRP-IR. A subsequent stimulation with capsaicin in a 2.5 mmol/l Ca2(+)-containing superfusion solution was not less effective to release CGRP-IR than in tissues which had not been pre-exposed to capsaicin. At 18 degrees C, the capsaicin-evoked release of CGRP-IR was reduced to 20% of the value obtained by the same dose (0.3 mumol/l for 5 min) of capsaicin at 37 degrees C. Comparison of the desensitizing effect of 0.3 and 0.1 mumol/l capsaicin at 18 degrees C and 37 degrees C, respectively, showed significant inhibition of desensitization at 18 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096300 TI - Effects of bepridil and lidocaine on the intraventricular conduction in acutely ischaemic and infarcted canine myocardium. AB - Effects of bepridil, an antiarrhythmic and antianginal drug, on intraventricular conduction in acutely ischaemic and infarcted myocardium were examined in anaesthetized dogs, and compared with those of lidocaine. Bepridil at doses of 2 and 5 mg/kg markedly prolonged the conduction time of a premature excitation induced by a ventricular stimulation in the infarcted zone. The effect of bepridil was dependent on a coupling time of the stimulation. Bepridil showed a marked effect at a coupling time of 150 ms, while it showed no significant effect at a prolonged coupling time of 1 s. In other words, the effect of bepridil was interval-dependent. Lidocaine showed a similar interval-dependent effect, but the effect of lidocaine at a longer coupling time was less than that of bepridil. The premature stimulation produced severely delayed conduction which resulted in reentrant beats. Bepridil blocked these conductions, thereby preventing reentrant beats. In contrast to the depressant effect of bepridil in the infarcted myocardium, bepridil prevented the prolongation of conduction time during acute ischaemia. The alternation of the ST-T complex during acute ischaemia which is also an important arrhythmogenic factor was also attenuated by bepridil. Contrary to bepridil, lidocaine significantly enhanced the conduction delay and the alternation in the ST-T complex. In conclusion, bepridil as well as lidocaine showed an interval-dependent depression of the conduction in the infarcted zone of the heart, whereas during acute ischaemia bepridil in contrast to lidocaine attenuated the conduction delay and ST-T alternans. PMID- 2096301 TI - Concentration- and rate-dependent electrophysiological effects of restacorin on isolated canine Purkinje fibres. AB - The cellular electrophysiological effects of restacorin, a new antiarrhythmic agent were studied using conventional microelectrode techniques in isolated dog cardiac Purkinje fibres. Restacorin (1-30 mumol/l) decreased the maximum rate of rise of the action potential upstroke and action potential amplitude while action potential duration measured at 90% of repolarization was shortened in a concentration-dependent manner during pacing at a constant basic cycle length of 500 ms. The effect of 10 mumol/l restacorin on maximal rate of rise of the action potential upstroke and on action potential duration measured at 90% of repolarization were also studied while varying the constant pacing cycle length between 300 and 5000 ms. The results of these studies indicated a rate-dependent effect of restacorin on the action potential characteristics examined. After abrupt changes in cycle length, 10 mumol/l restacorin slowed the fast component of the relation for restitution of action potential duration from 155.3 +/- 5.2 ms (control, n = 6) to 217.1 +/- 17.8 ms (n = 6, P less than 0.05). In the presence of restacorin (10 mumol/l), a second slow component for recovery of maximal action potential upstroke rising velocity was expressed having a time constants of 8.5 +/- 1.2 s. The range of premature action potential durations was significantly decreased (by 57.1%, P less than 0.01) by 10 mumol/l restacorin. These results indicate that the cellular electrophysiological effects produced by restacorin in dog cardiac Purkinje fibres best resemble those produced by recognized class Ic antiarrhythmic drugs. PMID- 2096302 TI - Platelet-activating factor (PAF) inhibitory profile of KO-286011 on blood platelets in vitro and in vivo. AB - A newly synthesised structural analogue of PAF, coded KO-286011 (1-O-hexadecyl-2 O-ethyl-rac-glycero-3-phosphoric acid 4-(N,N-dimethylamino)pyridinium butylester), was proved for its ability to inhibit PAF-mediated platelet responses in vitro and in vivo. The compound inhibited effectively the PAF induced aggregation and secretion of human and rabbit platelets. In contrast, there was little influence on ADP-, collagen-, and arachidonic acid-triggered platelet responses. Schild-analysis of aggregation data ascertained in human platelet-rich plasma was consistent with a simple competitive antagonism and yielded a pA2 of 6.44. Proaggregatory activity of KO-286011 was excluded turbidimetrically as well as by means of a single cell counting technique. [3H]PAF binding studies provided evidence that KO-286011 exerts its inhibitory action at the PAF-receptor level. A significant inhibition of the ex vivo PAF induced platelet aggregation was found after i.v. administration of 0.5 mg/kg KO 286011 to rabbits. The effect was most pronounced 5 min after dosing the inhibitor and detectable over a period of 30 min. Intravenous administration of 10 and 25 micrograms/kg KO-286011 to guinea pigs prevented dose-dependently the PAF-induced formation of thromboxane A2. The PAF-inhibitory action of KO-286011 was more potent than that of the ginkgolide BN 52021. PMID- 2096303 TI - Demonstration of dopamine DA-1 receptor sites in rat juxtaglomerular cells by light microscope autoradiography. AB - The binding of the selective DA-1 receptor antagonist [3H]-SCH 23390 in sections of rat kidney was studied using combined in vitro biochemical radio-receptor assay and autoradiography. [3H]-SCH 23390 was bound to sections of rat kidney in a manner consistent with the labeling of DA-1 receptors with a dissociation constant value of 4.2 nmol/l and a Bmax value of 180.6 fmol/mg protein. Light microscope autoradiography revealed a dense accumulation of silver grains in juxtaglomerular cells and in proximal convoluted tubule cells. These findings suggest that the stimulation of renin release elicited by dopamine and DA-1 receptor agonists may be mediated by the activation of DA-1 receptors located on juxtaglomerular cells. PMID- 2096304 TI - [Pulp response to restorative materials]. AB - Restorations may affect the pulp negatively, rather due to microleakage than to toxic properties of the materials used. Hyperalgesia occurs more frequently after restoration with composite resins than with amalgam, though the resins in contrast to amalgam may be bonded to the enamel margins. A number of recommendations are presented in order to minimize the marginal gap between cavity walls and amalgam and to prevent marginal fracture. PMID- 2096305 TI - [Microleakage and pulp protection]. AB - Clinically undetectable leakage around amalgam and composite restoration, normally referred to as microleakage, will cause a bacterial invasion of the dentinal tubules. Such an invasion demands precautions. Although without a protective base many patients do not have complaints, this does not imply that the pulp is not affected. Therefore, dentin which is exposed during dental treatment should always be sealed hermetically. Of the lining materials, calcium hydroxide and glass-ionomer are strongly favourable among the general practitioners. Disadvantages of these popular materials justify, however, the conclusion that other linings are to be preferred. PMID- 2096306 TI - [Characterizing the smear layer]. AB - The smear layer was first described as a debris layer which is left on all cavity walls following tooth preparation. It is composed of an outer contiguous layer of amorphous instrumentation matrix which covers all cavity walls, and a deeper zone of matrix plugs which obturate the cut tubules. Recent scanning electron microscopic (SEM) studies have characterized the smear layer as mineralized collagen fibers appearing as globules dispersed within an amorphous cutting matrix. Removal of smear plugs increases the outward hydraulic conductance (Lp) of dentinal fluid flow which may lead to dentinal hyperalgesia, bacterial infection and pulp pathosis if left untreated. PMID- 2096307 TI - [Bonding to dentin]. AB - The development of adhesive systems is mainly concentrated on the possibility of chemical bond formation. Although glass-ionomer bonds chemically both to enamel and dentin and proved to be a successful restorative in class V restorations, the ultimate goal is to accomplish a strong and durable bond with the esthetic composite materials. The mechanism of chemical bonding to dentin apatite and collagen is discussed for a number of recently developed dentin bonding agents. Bond strengths up to 15 MPa can be obtained, but these are still not able to resist the forces of polymerization shrinkage of the composite materials. PMID- 2096308 TI - [Complete sealing of dental cavities]. AB - Notwithstanding the adhesive capacity of composites and glass-ionomers, bonding is jeopardized by the curing shrinkage. Curing contraction in an adhesive restoration is reduced partly by elastic strain, partly by plastic flow and partly by local fracture. With respect to the class V composite restoration, material properties are discussed and selection criteria are given in order to achieve a perfect marginal seal. PMID- 2096309 TI - [Long term results of overdentures]. AB - This article describes the long term results of overdenture therapy. The main goal--prevention of alveolar bone loss--appears to be achieved. Without preventive measures caries and periodontal diseases are frequently found. With the use of fluoride, possibly combined with chlorhexidine, and an optimal oral hygiene the prognosis is good. Taking these results into account the preservation of (roots of) teeth is highly recommended in the scope of preventive prosthodontics. PMID- 2096310 TI - [Microleakage: evaluation and treatment]. AB - Microleakage is a biological phenomenon with several implications. The affective component patient hyperalgesia (pain/hypersensitivity) of dentin which is a function of episodic hydrodynan (fluid) movement. The effective component is the disease process which signals the dentin-pulp complex to respond by disposition of sclerotic and/or reparative dentin. Vital dentin is an extension the pulp, presenting the first line of response to the consequences of microleakage. Recent data has demonstrated a correlation between pulp response and material biocompatibility when microleakage is prevented. Dentin-pulp healing is ensured when a proper hermetic seal is provided to control prevent microleakage. A critical evaluation of various clinical procedures is discussed. PMID- 2096311 TI - Mad cows and Englishmen: bovine spongiform encephalopathy. PMID- 2096312 TI - Pilot study of the prevalence of major neurologic disorders in a rural population of India. AB - A study of the prevalence of major neurologic diseases will be carried out in a rural population near Ballabgarh. India, using the World Health Organization protocol for epidemiologic studies of neurologic disorders and other internationally standardized survey techniques, screening procedures, and diagnostic criteria. Before applying any protocol developed in one population to another population, it must be intensively tested. Here, we describe the adaptation of the WHO protocol to the local conditions in rural Ballabgarh, and the findings of the pilot study conducted to test the protocol. PMID- 2096313 TI - 5-year study of incidence rates of hospitalized cases of head injuries in the US Army. AB - Incidence rates of hospitalized head injury cases in the US Army were calculated by age, race, and sex. Skull fractures and intracranial diagnoses were found almost exclusively in males. For concussion, white males were at about 1.5 times greater risk compared to black males, and white females were at about 2 to greater than 3 times the risk compared to black females. For other intracranial injury, males were at 1.25 to about 2 times increased risk compared to females, white males were at about 1.5 times risk compared to black males, and white females were at 1.5-2 times greater risk compared to black females. Ten percent of head injury cases had an alcohol-related additional diagnosis and 97% of these were found in males. PMID- 2096314 TI - A case control study of some hematological and biochemical variables in acute stroke and their prognostic value. AB - Hematocrit, total white cell and platelet counts, plasma urea and creatinine concentrations were estimated in 291 patients (mean age 70 +/- 12 years) admitted consecutively over a 6-month period to a district general hospital with acute stroke. Urinary albumin/creatinine ratio was also determined in a subgroup of patients during a follow-up visit 3 months after ictus. Results were compared with those from age- and sex-matched community controls. Total white cell count was elevated in all types of stroke compared with values from control subjects. Platelet count, plasma urea and creatinine concentrations were higher and the plasma albumin/globulin ratio was lower among patients with ischemic stroke. Elevated total white cell count, urea and creatinine, which were of prognostic significance, were found to be associated with the severity of stroke as indicated by the Glasgow coma score, and did not have any independent prognostic value. Elevated hematocrit was not shown to be a risk factor and did not have any prognostic significance. A low plasma albumin/globulin ratio, an index of plasma viscosity, was a possible risk factor for ischemic strokes. Urinary albumin/creatinine ratios in the highest quintile increased the risk of stroke 13 fold. PMID- 2096315 TI - Hereditary ataxias: epidemiological aspects. AB - Hereditary ataxias, hereditary spastic paraplegia and Charcot-Marie-Tooth syndrome (HA) are chronic progressive neurological diseases. Epidemiologic studies of these disorders are few. In a geographically well-defined Danish population, we present incidence rates, cumulated incidence rates and prevalence for patients with HA based on modern continuous-time survival analysis techniques. From these, prevalence has been estimated to be 6.06 per 10(5) in the 10 to 50-year-old population. Combined risk of HA was found to be 0.16% for women and 0.20% for men up to their 51st birthday. PMID- 2096316 TI - Histomorphometric and histopathological study of the human cricopharyngeus muscle: in health and in motor neuron disease. AB - Abnormalities in muscle histology have been reported frequently for the cricopharyngeus muscle of patients with oculopharyngeal muscular dystrophy, motor neuron disease and other neurological disorders in which dysphagia is a common clinical sign. However, there are few detailed reports of the normal structure of this muscle nor quantitative baseline data with which to compare the diseased state. In this study, cricopharyngeus muscles from 21 healthy individuals and four patients with motor neuron disease underwent quantitative histological and histochemical examination. In addition to the extensive connective tissue content (40%), comprising abundant elastic fibres, cricopharyngeus muscles from normal individuals possessed small calibre striated muscle fibres (mean narrow diameter 30 microns) of widely varying size (coefficient of variation 41%). The majority of fibres were histochemically type I (82%) and highly oxidative. All muscles comprised numerous muscle fibres with aberrant histological and histochemical features (internalized nuclei, 'ragged red' crescents, splits, degenerating fibres, 'moth-eaten' fibres, or nemaline rods.) The histomorphometric and histopathological features were similar in males and females and some showed a correlation with age. There were increases in fibre size and roundedness and decreases in the numerical density and percentage of type I and split fibres in the specimens from older individuals. Cricopharyngeus muscles from patients with motor neuron disease were not significantly different from the controls for most parameters. It is therefore suggested that previous descriptions of specific cricopharyngeal pathology accompanying neuromuscular disease or dysphagia be interpreted with caution. The importance of obtaining normal structural, morphometric and histopathological data from muscles other than the usually biopsied limb muscles, is emphasized. PMID- 2096317 TI - Neuronal cytoskeletal lesions induced in the CNS by intraventricular and intravenous aluminium maltol in rabbits. AB - The antigenicity of neuronal cytoskeletal lesions was studied immunohistochemically in adult New Zealand white rabbits after intraventricular (subacute) and intravenous (chronic) administration of a water-soluble aluminium compound, aluminium (Al) maltol. After short-term intraventricular administration, rabbits developed widespread neurofibrillary degeneration (NFD) involving pyramidal neurons of the isocortex and allocortex, projection neurons of the diencephalon, and nerve cells of the brain stem and spinal cord. There was a predilection for motor neuron involvement and for the infratentorial portions of the neuraxis. Perikarya and proximal neurites were especially affected. Bundles of 10 nm filaments were frequently present. Three of the animals treated intravenously for 12 weeks or longer displayed NFD in the oculomotor complex and in the pyramidal neurons of the occipital isocortex. Following either mode of administration, the affected neurons exhibited immunostaining with a panel of monoclonal antibodies (MAbs) against phosphorylated (SMI-31), non phosphorylated/phosphatase-sensitive (SMI-32), and dephosphorylation-independent (SMI-33) epitopes of high and middle molecular weight neurofilament (NF) protein subunits. They were non-reactive with MAbs to microtubule-associated protein 2 and the class III neuron-associated beta-tubulin isotype. Our findings indicate that intraventricular Al maltol produces similar, but more widespread degeneration of projection-type neurons than the less water-soluble Al compounds as reported by others. The NFD lesions are compared with those of senile dementia of the Alzheimer type (SDAT) and motor neuron disease. PMID- 2096318 TI - Proceedings of the eighteenth meeting of the British Neuropathological Society. Birmingham, 12-13 July 1990. Abstracts. PMID- 2096319 TI - Posttetanic potentiation of primary response and late negative wave in the somatosensory region of the cortex of the cat. AB - The experiments were carried out on cats under nembutal anesthesia. Stimulation of the ventroposterolateral nucleus of the thalamus or the white matter by a single stimulus elicited a primary response in the middle layers of the somatosensory cortex, and after it, a late negative wave, the duration of which reaches 40-70 msec. This potential does not have dipole reflection on the surface of the cortex and is apparently generated primarily by stellate cells. As a result of the tetanization of the ventroposterolateral nucleus or the white matter, a sharp increase in the amplitude of the late negative wave is observed, i.e., its posttetanic potentiation, while the primary response changes to a significantly lesser degree. Posttetanic potentiation is observed for 2-2.5 h. Posttetanic potentiation of the late negative wave is probably governed by processes occurring at the level of the middle layers of the cerebral cortex. PMID- 2096320 TI - Hyperbaric oxygenation in comprehensive treatment of parkinsonism. PMID- 2096321 TI - Interaction of serotonin- and dopaminergic systems of the brain in mechanisms of latent inhibition in rats. AB - The activity of serotoninergic neurons of the medial raphe nucleus was turned off by local injection of the neurotoxin, 5,7-dihydroxytryptamine. Seven days later, a conditioned passive avoidance reaction was developed following 20 preexposures to the conditional stimulus (the presentation of the experimental chamber). As compared with the sham-operated control, in which 20 preexposures to the stimulus elicited latent inhibition, i.e., attenuation of the reproduction of the conditioned passive avoidance reaction, prolonged maintenance at the formed level, and lack of susceptibility to amnesia, all of the enumerated features were disturbed in animals administered the neurotoxin. The administration of haloperidol (0.5 mg/kg) 1 h prior to training reestablished the state of latent inhibition which had been disrupted by the switching off of the mesolimbic serotonin system. It is hypothesized that the process of the suppression of attention to the nonreinforced signals during the preexposure to the stimulus is achieved by the interaction of the serotoninergic and dopaminergic systems. PMID- 2096322 TI - Dependence of electrical activity of the amygdaloid complex on level of motivation and emotional state of the dog. AB - The effect of an increment in the power of the rhythmic activity of the amygdala during changes in the level of motivation in conditions of the dominance of alimentary or defensive motivation, irrespective of type, was discovered on the basis of spectral analysis of prolonged recordings of electrosubcorticograms of the amygdaloid complexes of three dogs. The resonance characteristics of the system responsible for the generation of this rhythm remain unchanged in the process, which allows explanation of the increase in the spectral peak by an increase in the inflow of afferent impulse activity into the amygdala. Summation of the influences of each of them is not observed in the presence of competing motivations, while a more complex influence on rhythm in the amygdala emerges. PMID- 2096323 TI - Pentagastrin modulation of sensitivity of neurons of the lateral hypothalamus to noradrenaline and dopamine. AB - The chemical sensitivity of neurons of the lateral hypothalamus of hungry and fed rabbits to pentagastrin (PG) and to the mediators, noradrenaline (NA) and dopamine (DA), was investigated utilizing indices which permit the assessment of the structural-functional organization of the impulse stream of nerve cells. It was demonstrated that the neurons of the lateral hypothalamus possess varied chemical sensitivity in the presence of alimentary motivation and during the satisfaction of the corresponding need. The microiontophoresis of PG changes the sensitivity of cells in hungry animals to a higher degree to DA (60%) than to NA (30%), while in fed animals, to a higher degree to NA (48%) than to DA (23%). The administration of NA against the background of the action of PG to fed rabbits decreased the percent of neurons with spike train complex activity. The number of cells in the deprived animals with impulse activity of a similar character decreased following the microiontophoresis of DA alone and DA against the background of the action of PG. It is concluded that PG exerts a modulating influence on the effects of NA and DA on the impulse activity of the neurons, and that the character of the effect of PG depends on the initial state of the animal. PMID- 2096324 TI - Comparison of coupling of impulse activity of cerebral cortical neurons and spatial synchronicity of the EEG. AB - The coherence of the EEG and the coupling of the impulse activity of neurons of the visual and sensorimotor areas of the neocortex of rabbits, recorded simultaneously from the same electrodes, were compared under chronic experimental conditions. An association was found between the presence and properties of the conjugated functioning of neurons and the coherence of the EEG at various frequencies. Greater coherence of the EEG was observed during the correlated functioning of neurons at frequencies of 3-4.5 Hz than during independent functioning. The neurons discharged in pairs, with a smaller delay between them at the highest level of EEG coherence, and a common source participating more often in their synchronization than at the lowest level of EEG coherence. PMID- 2096325 TI - Functional characteristics of the mature and developing brain following neuroimmunization: analysis of short-term plasticity in the rat hippocampus. AB - The influence of neuroimmunization by the total antigens of the cytosol fraction of hippocampal tissue or neocortical tissue on the indices of short-term plasticity in adult and developing (3 to 4 week old) Wistar rats has been investigated. Short-term plasticity was evaluated on the basis of changes in the slow-wave component of the focal potentials (FP) of the CA3 field of the hippocampus upon stimulation of the region of the dentate gyrus. The FP were recorded under nembutal anesthesia. In the groups of the hippocampus of adult and developing immunized rats, the greatest changes in short-term plasticity in the form of extreme intensification of the expressivity of the properties of paired facilitation and frequency potentiation were confined to the pyramidal layer. In the neocortex groups, the changes, as a rule, were less marked, and had the opposite sign; the main differences were found in the recording of the FP in the zone of the apical dendrites of the pyramidal neurons. It was noted that the focal activity of the young immunized animals is characterized by greater maturity as compared with the age norm. A conclusion is drawn regarding the different primary localization of the targets of the neuroimmune effect when antigens of different brain structures are used, namely hippocampus versus neocortex, and regarding the dependence of the physiological effect of neuroimmunization on the degree of maturity of the target structure. PMID- 2096326 TI - Neuronal activity of medial wall of frontal cerebral cortex of rats at various stages of learning. AB - The activity of neurons of the medial wall of the frontal cortex of the brain of rabbits was investigated during their performance of a task of delayed spatial choice. The recording of neuronal activity was carried out in two groups of animals which were at different stages of training. Different types of spatially selective neurons were found. The possible association of the character of the neuronal reorganizations with the level of learning of the animal is discussed. PMID- 2096327 TI - Modeling of latent inhibition in rats by activation of the central serotoninergic system. PMID- 2096328 TI - Features of formation of conditioned responses in isolated LPa3 neuron of the edible snail. PMID- 2096329 TI - Pathways of activation and change of the endocrine function of testes elicited by effect of presence of the female. PMID- 2096330 TI - Mechanism of origination of neuroparalytic keratitis. PMID- 2096331 TI - Features of the ensemble organization of the human cerebral cortex from birth to 20 years of age. PMID- 2096332 TI - Nutritional therapy for infants with diarrhea. AB - The appropriate choice of treatment for infants with diarrhea has long provoked debate. Growth of infants with diarrhea is adversely affected by associated diseases including anorexia, malabsorption, catabolic response to infection, and iatrogenic starvation. To prevent the negative effects of diarrhea on the nutrition of infants, continued feeding during the active and early convalescent phases has been recommended. Although this concept is not new, until recently it has been little used in the treatment of diarrhea. In this article we examine the current knowledge about, and trends in, feeding infants with diarrhea. We will discuss treatments for the well-nourished infant with acute diarrhea, the infant with prolonged diarrhea, and the malnourished infant. Information regarding the use of local staples will also be provided. PMID- 2096333 TI - Guarding against cellular glutathione deficiency. PMID- 2096334 TI - Triacylglycerol metabolism and hypertriglyceridemia. PMID- 2096335 TI - Postprandial lipemia and reverse cholesterol transport. PMID- 2096336 TI - Biotin in animal nutrition. PMID- 2096337 TI - How glucose gets into cells. PMID- 2096338 TI - Brain cholecystokinin receptors and satiety. PMID- 2096339 TI - The dangers and advantages of deciding on therapy on the basis of theory. PMID- 2096341 TI - Results from 7-mm bilateral recessions of the medial rectus muscles for congenital esotropia. AB - We reviewed the surgical records of 77 patients who had undergone 7-mm bilateral medial rectus recessions for large-angle congenital esotropia. The mean age of onset of esotropia in these patients was 3.5 months, and the mean age at the time of surgery was 12.9 months. The mean preoperative deviation was 69 delta of esotropia. This procedure resulted in satisfactory horizontal alignment in 47 patients (61%) at their latest follow-up examination (mean, 27 months; range, 6 months to 6 years). The esotropia was undercorrected in 21 patients (27%) and overcorrected in nine (12%). Amblyopia was noted in 30%, oblique muscle dysfunction in 44%, and dissociated vertical deviation in 36% of the patients. Regression analysis of multiple variables showed alignment at 6 weeks to be the only predictor of the final outcome (R = .83). Extramacular fusion was achieved in 10 of 11 patients for whom reliable sensory data were available. The mean age at surgery of these patients was 9.7 months. Seven-millimeter bilateral medial rectus recessions are an effective alternative to three- and four-muscle procedures in the initial treatment of large-angle congenital esotropia during infancy. PMID- 2096340 TI - Comparison of the effects of two viscoelastic agents, Healon and Viscoat, on postoperative intraocular pressure after penetrating keratoplasty. AB - Sixty-two patients undergoing penetrating keratoplasty were randomized to receive Healon (1% sodium hyaluronate) or Viscoat (3% sodium hyaluronate and 4% chondroitin sulfate) as a means of maintaining the anterior chamber during surgery. Neither viscoelastic agent was irrigated from the eye at the end of the procedure. Intraocular pressures (IOPs) were measured at 4, 10, 24, and 72 hours postoperatively. For the Healon group, IOPs were 16.52, 23.50, 28.31, 23.27, and 16.03 mm Hg at baseline and at the four follow-up periods, respectively. For the Viscoat group, they were 19.10, 28.33, 23.48, 18.62, and 16.17 mm Hg at those points, respectively. IOPs were significantly elevated over baseline in the Healon group at 4, 10, and 24 hours, and in the Viscoat group at 4 and 10 hours. There were no statistically significant differences between the Healon and Viscoat groups at 4, 10, and 72 hours. At 24 hours, the Healon group had a mean pressure rise over baseline of 6.5 mm Hg, while the Viscoat group had returned to baseline levels (P = .02). We conclude that both Healon and Viscoat raise postoperative IOPs, but that Healon appears to elevate IOPs for a longer period after surgery than Viscoat. PMID- 2096342 TI - Intraocular gas injection in the treatment of cornea-lens touch and choroidal effusion following fistulizing surgery. AB - Five eyes with large choroidal detachments and flat anterior chambers following fistulizing surgery were treated with injection of perfluoropropane into the anterior chamber. In all cases the choroidal detachments resolved within 4 days, without the need for drainage. Three phakic eyes developed anterior capsular opacification in the area of contact between the gas bubble and the anterior capsule. Injection of perfluoropropane is recommended as a simple and effective approach to the management of choroidal detachments with flat anterior chamber in pseudophakic eyes and in cataractous phakic eyes. PMID- 2096343 TI - Quantitative CW Nd:YAG pars plana transscleral photocoagulation in postmortem eyes. AB - The effect of different types of burns and numbers of lesions on, and the role of initial pressure head in, the rate of aqueous outflow was studied in enucleated human and porcine eyes. Noncontact and contact CW Nd:YAG laser applied to human eyes 3 mm posterior to the limbus produced a 34% and 51% increase, respectively, in outflow as compared with controls (P = .01). In porcine eyes, outflow increased directly with the number of noncontact burns as well as with the amount of perfusion pressure. Our results suggest that intraocular pressure and outflow are functions of both the intensity of irradiation and the surface area treated, and that each individual pressure head may require an optimal pars plana area of treatment of therapeutic degree to lower pressure and yet prevent overfiltration and phthisis. Our results also suggest that there may be a passive transneuroepithelial and transscleral outflow component in clinical laser cycloablation and, therefore, a need to grade laser treatments in order to prevent visual loss through unnecessary injury. PMID- 2096344 TI - Clearance of fluorescein incorporated into microspheres from the cornea and aqueous after subconjunctival injection. AB - The clearance of sodium fluorescein from the cornea and aqueous humor of albino rabbits was quantitated after subconjunctival injection of fluorescein entrapped in lactide/glycolide (group 1) and lactide (group 2) microspheres. Seven hours after injection, approximately equal concentrations of fluorescein were measured in both groups in the cornea and aqueous. Fluorescein concentrations in the cornea were more than three times those found in the aqueous. Fluorescein concentrations in both groups decreased at 22 hours, and remained constant at 46 hours. Corneal fluorescein levels in group 2 were slightly higher than in group 1 at 22 and 46 hours. All eyes showed conjunctival inflammatory reaction at the injection sites after 6 days. One eye showed conjunctival necrosis at the injection site after 13 days. PMID- 2096345 TI - Iontophoresis for eyelid anesthesia. AB - Local anesthesia is appropriate for eyelid surgery, but patients fear the pain of injections. We evaluated iontophoresis of lidocaine for eyelid skin anesthesia to pinprick pain sensation in normal subjects, and prior to regional infiltration of the anesthetic agent in patients undergoing eyelid surgery. After iontophoresis of lidocaine hydrochloride 4% solution to one randomly chosen eyelid, pinprick skin sensation was tested in a double-masked manner. Subjective pain scores of 10 subjects were significantly less (P less than .008) on the iontophoresis treated eyelids (0.25) than on the untreated eyelids (2.55). Nine patients undergoing bilateral upper eyelid surgery had iontophoresis applied to one randomly chosen eyelid prior to the usual anesthetic injections. In this double-masked evaluation, patients reported significantly less pain (P less than .02) on the treated eyelids (1.4) than on the untreated eyelids (4.7). We conclude that iontophoresis is effective for achieving short-term, superficial anesthesia of eyelid skin. PMID- 2096346 TI - Scleral fixation suture for dislocated posterior chamber intraocular lens. AB - The posterior dislocation of an intraocular lens is a serious complication of extracapsular cataract extraction with implantation of a posterior chamber intraocular lens. We describe a method of repositioning and suturing such a lens, using pars plana techniques. The method we recommend has several advantages over previously described methods, including the use of radially oriented scleral fixation sutures. PMID- 2096347 TI - Retinal detachment adherent to posterior chamber IOL after Molteno implant surgery. AB - A patient with refractory glaucoma 1 year after cataract extraction and trabeculectomy had Molteno implant surgery. Three days after surgery a kissing choroidal effusion and retinal detachment adherent to the posterior chamber IOL were detected. Repeated choroidal taps were unsuccessful. Removal of the Molteno implant, vitrectomy, and silicone oil injection were required to reattach the retina. PMID- 2096348 TI - Intraocular pressure profile during general anesthesia. AB - The effect of some anesthetic drugs on intraocular pressure (IOP) was studied in 120 normal healthy patients undergoing non-ophthalmic surgical procedures. IOP rose significantly following the injection of succinylcholine (SCh) alone, or when such injection had been preceded by a pretreatment with a "self-taming" dose of SCh or d-tubocurarine (d-Tc). Though the rise in IOP after diazepam pretreatment was significant, the magnitude was lower than that observed in the groups pretreated with the other two agents. Halothane brought the IOP down faster and lower than ether. SCh is unsafe for intubation for the administration of general anesthesia in cases involving penetrating ocular injuries. It can, however, be used safely for routine ophthalmic surgery, providing that 8 minutes are allowed to elapse between injection and corneal or scleral incision. Halothane is preferred to ether, since the former lowers IOP faster and in a greater amount than the latter. PMID- 2096349 TI - Dual camera sequencer for microsurgical documentation. AB - All currently available documentary formats have inherent compromises. The use of both video and 35-mm still photography seems to be a practical solution but introduces image quality loss (when using a beam splitter type of dual camera adapter) or increased complexity of operation and resultant surgeon distraction (when using a movable mirror type of dual camera adapter). An electronic sequencer was designed to simplify the operation of a movable mirror type of dual camera adapter, permitting the efficient production of high image quality video recordings and 35-mm slides. PMID- 2096350 TI - On the practicalities of eye camp cataract extraction and intraocular lens implantation in Nepal. AB - Based on our experience in Nepal, we discuss the practicalities of performing extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation in the context of the third-world eye camp. At slightly less than 30 minutes per case, while not as quick as an intracapsular cataract extraction (ICCE) with a Graefe section, the trade-off between vision result and operation time, according to patients, is very much in favor of the ECCE/IOL technique. Also, although IOLs remain expensive, by using donated lenses, the overall costs of providing ECCE/IOL surgery need not exceed those of providing ICCE. PMID- 2096351 TI - Intraocular lens implantation in India. PMID- 2096352 TI - Panretinal photocoagulation using the Volk Quadraspheric lens. PMID- 2096353 TI - Oculocutaneous albinism in Cameroon. A 15-year follow-up study. AB - Oculocutaneous albinism in Cameroon was studied from 1972 to 1987. Two hundred and seventy-three albinos (160 males and 113 females) were registered. The sex ratio of 1.42 (male/female) was significantly different from unity but this apparent discrepancy may be explained by social and geographical reasons. The highest prevalence occurred in the Bamileke group (190/273 albinos, i.e., 70%) for which the rate was 1 in 7,900, using an estimate of 1,500,000 Bamileke people. The high frequency of the albino gene was thought to result from a greater inbreeding tendency, to the special organization of the Bamileke society in mini-states or kingdoms and to a founder effect in the case of Balengou kingdom. The death of albinos was mainly due to skin cancer induced by solar radiation during the second, third or fourth decade. Cameroon, located from 2 degrees to 12 degrees above the equator, is sunny throughout the year. Registering all albinos early in life, educating them to prevent the damaging effect of the sun (protective clothing, sun-screening agents and indoor occupations), detecting and treating premalignant and malignant lesions are of great importance in this country. PMID- 2096354 TI - X-linked ocular albinism. Characteristic pattern of affection in female carriers. AB - The authors report on a family with X-linked ocular albinism. Examined were one of three affected males and eight females. Six women were carriers and showed iris retroillumination and typical abnormalities of the fundus. The patchy or striated hypopigmentation of the retinal pigment epithelium is thought to be due to random inactivation of the paternal or maternal X-chromosome respectively. The pattern of affection however represents a nonrandom embryological developmental pattern of the retinal pigment epithelium. PMID- 2096355 TI - Hypomelanosis of Ito (incontinentia pigmenti achromians). Ophthalmological evidence for somatic mosaicism. AB - The authors report on a ten-year-old boy with hypomelanosis of Ito. He suffered from epileptic seizures and exhibited typical generalized partial skin hypomelanosis in whorl-like and striated pattern following Blaschko's lines. The fundi showed patchy, mottled hypopigmentations becoming increasingly striated in the periphery with a general orientation to the optic nerve head. This pattern of affection reminds of the retinal findings in carrier women for X-linked ocular albinism. Magnetic resonance imaging revealed multiple small areas of increased relaxation time scattered in the white matter of the brain, which are interpreted as porencephalic cysts. These clinical findings suggest somatic cell mosaicism even though the cytogenetic study was not conclusive. PMID- 2096356 TI - Familial pericentric inversion of chromosome 11 in a child with sporadic unilateral retinoblastoma. AB - The authors treated a 12-month-old Japanese boy with sporadic unilateral retinoblastoma and hereditary chromosomal inversion inv(11)(p11q23). This chromosomal inversion was also present in the father of the boy. Cytogenetic analyses of the mother and sister were normal. Retinoblastoma is associated with constitutional deletion of the long arm of chromosome 13. The breakpoint in the chromosome 11q23 region is involved in several malignant hematological diseases, and may be important in malignant transformation. Therefore, a large number of such patients with pericentric inversion of chromosome 11 has to be identified before significance of this chromosomal abnormality can be determined. PMID- 2096357 TI - Golden tapetal reflex in male patients with X-linked retinitis pigmentosa. Case report and practical implications. AB - The golden tapetal reflex in the ocular fundus is considered pathognomonic of the carrier state in some families with X-linked retinitis pigmentosa (XRP). Reports concerning affected males with this characteristic reflex are scarce. A six-year old boy with XRP having a tapetal reflex is described. Recently the tapetal reflex has drawn attention in linkage studies. XRP is probably genetically heterogeneous and has at least two genetic forms. The finding of a tapetal reflex in one or more female carriers in a family with XRP may be helpful in differentiating between these two genetic forms. PMID- 2096358 TI - Dental abnormalities as a component of the Laurence-Moon-Bardet-Biedl syndrome. AB - Previous reports have described the diversity of the phenotypic expression of the Laurence-Moon and Bardet-Biedl syndrome. This report describes two brothers whose features include the previously unreported defect of oligodontia in addition to retinitis pigmentosa, hypogenitalism, strabismus, short stature, and developmental delay. The reports over the last century have emphasized the varied expression from family to family and even differences among members of the same family. This report broadens the already pleomorphic nature of this syndrome. PMID- 2096359 TI - Pars planitis in father and son. AB - The authors examined a family in which father and son presented with pars planitis. Both of them and the paternal grandparents were HLA typed; no association between HLA antigens and pars planitis was found. Present and previous data suggest a relation between pars planitis and allergic predisposition. PMID- 2096360 TI - Appearance and reality (1): A number of ideas. PMID- 2096361 TI - Coherence determines speed discrimination. AB - The visual system must determine which elements in a scene to regard as parts of a single object and which to regard as different objects. We can create stimuli that are ambiguous, ie consistent with more than one interpretation, and ask in what situations the stimulus elements are interpreted as part of a single object and when they are interpreted as multiple objects. The ambiguous stimuli in this study were moving plaid patterns--the sum of two drifting gratings with different orientations. Observers may see a rigid coherent plaid object moving in one direction, or may see two gratings moving in different directions sliding over one another. When the gratings have similar contrasts they appear to cohere and only the plaid speed is perceptually available; when the gratings have different contrasts they appear to slide and only the speeds of the gratings are perceived. Coherence thus determines what speed information is passed to higher stages of motion processing. A two-stage model of plaid motion perception is presented which agrees with the model proposed by Adelson and Movshon and extends it, detailing the relationship between coherence and speed discrimination. PMID- 2096362 TI - The relationship between visual persistence and event perception in bistable motion display. AB - Observers viewed two alternating frames, each consisting of three rectangular bars displaced laterally by one cycle in one frame with respect to the other. At long interframe intervals (IFIs) observers perceived a group of three bars moving as a whole (group motion), and at short IFIs the overlapping elements in the two frames appeared stationary, while the third element appeared to move from one end of the display to the other (element motion). The upper temporal limit for perceiving element motion was reduced when bars with blurred edges were used and when either frame duration or bar size was increased. However, when inner and outer elements had different sizes, the element motion percept was dominant up to 230 ms IFI. These findings may be interpreted in terms of spatial tuning of motion mechanisms involved in the perception of bistable apparent motion. PMID- 2096363 TI - The magic wand: a new stereokinetic anomalous surface. AB - When a disc with two dots stuck on it a few centimetres apart is set in slow rotatory motion, the two dots appear displaced in depth and rigidly connected to form the two extremities of a rod. The rod appears as a diaphanous transparent object, slightly tinted to the same colour as the dots. Experimental analysis of the phenomenon shows that it is different from previously observed 'moving phantoms', 'motion-induced contours', and 'stereokinetic induced phantoms'. But it shows similarities with all three phenomena: the colour spreading along the apparent rod is facilitated by low illumination and is clearly visible under high illumination with bright colours only; it is seen only when the two dots appear to move with apparent displacement in depth and not when they appear to lie on the plane of the disc. When line-drawn circles instead of full colour dots are used, the anomalous surface of the rod appears to have colourless vitreous transparency. With half-line circles it is clearly visible as an opaque rod of the same colour as the background. When squares or diamonds are used instead of dots, a three-dimensional prism can be observed which has similar appearance to the rod. PMID- 2096364 TI - Visual localization and estimation of extent of target motion during ocular pursuit: a common mechanism? AB - The ability to localize a visual target and to estimate the distance through which it moves was studied during ocular pursuit. In the first experiment observers had to localize the position of a visually tracked moving target when they heard an acoustic signal. The signal was sounded near the beginning or near the end of the motion. The distance between the perceived positions was shorter than the distance between the corresponding physical positions of the target. The 'shortening' became more pronounced with higher tracking velocity. In another condition the observers estimated the length of the motion path between two successive sound signals, one presented near the beginning and one near the end of the motion. The length of path travelled was underestimated, the effect being stronger with higher tracking velocity. In the second experiment this effect of velocity on the underestimation of distance was shown to exist only during ocular pursuit and not during steady fixation. The hypothesis that localization and estimation of distance during ocular pursuit share a common mechanism is discussed. PMID- 2096365 TI - An acceleration illusion caused by underestimation of stimulus velocity during pursuit eye movements: Aubert-Fleischl revisited. AB - When the eyes pursue a fixation point that sweeps across a moving background pattern, and the fixation point is suddenly made to stop, the ongoing motion of the background pattern seems to accelerate to a higher velocity. Experiment I showed that this acceleration illusion is not caused by the sudden change in (i) the relative velocity between background and fixation point, (ii) the velocity of the retinal image of the background pattern, or (iii) the motion of the retinal image of the rims of the CRT screen on which the experiment was carried out. In experiment II the magnitude of the illusion was quantified. It is strongest when background and eyes move in the same direction. When they move in opposite directions it becomes less pronounced (and may disappear) with higher background velocities. The findings are explained in terms of a model proposed by the first author, in which the perception of object motion and velocity derives from the interaction between retinal slip velocity information and the brain's 'estimate' of eye velocity in space. They illustrate that the classic Aubert-Fleischl phenomenon (a stimulus seems to be moving slower when pursued with the eyes than when moving in front of stationary eyes) is a special case of a more general phenomenon: whenever we make a pursuit eye movement we underestimate the velocity of all stimuli in our visual field which happen to move in the same direction as our eyes, or which move slowly in the direction opposite to our eyes. PMID- 2096366 TI - Apparent brightness enhancement in the Kanizsa square with and without illusory contour formation. AB - The perceived strength of darkness enhancement in the centre of surfaces surrounded or not surrounded by illusory contours was investigated as a function of proximity of the constituent elements of the display and their angular size. Magnitude estimation was used to measure the perception of the darkness phenomenon in white-on-grey stimuli. Darkness enhancement was perceived in both types of the stimuli used, but more strongly in the presence of illusory contours. In both cases, perceived darkness enhancement increased with increasing proximity of the constituent parts of the display and with their angular size. These results suggest that the occurrence of darkness (or brightness) enhancement phenomena in the centre of the displays is not directly related to illusory contour formation. PMID- 2096367 TI - Ambiguous fluidity and rigidity and diamonds that ooze! AB - If white hemicircles rotate over the edges of a black diamond, there occurs an ambiguity of rigidity and motion. As the hemicircles obscure the vertices of the diamond, the figure transforms from a diamond to a rotating, nonrigid cross made of a tar-like fluid. When the corners reappear, the stimulus again becomes a rigid, solid diamond. Visibility of the vertices implies rigidity. If white squares are rotated, fluidity is not perceived. If the diamond has sawtooth edges and the hemicircles are rotated, no fluidity is perceived. Similarly, if illusory contours suggest the amodal completion of the vertices, rigidity is maintained. PMID- 2096368 TI - Transparency: relation to depth, subjective contours, luminance, and neon color spreading. AB - The perception of transparency is highly dependent on luminance and perceived depth. An image region is seen as transparent if it is of intermediate luminance relative to adjacent image regions, and if it is perceived in front of another region and has a boundary which provides information that an object is visible through this region. Yet, transparency is not just the passive end-product of these required conditions. If perceived transparency is triggered, a number of seemingly more elemental perceptual primitives such as color, contour, and depth can be radically altered. Thus, with the perception of transparency, neon color spreading becomes apparent, depth changes, stereoscopic depth capture can be eliminated, and otherwise robust subjective contours can be abolished. In addition, we show that transparency is not coupled strongly to real-world chromatic constraints since combinations of luminance and color which would be unlikely to arise in real-world scenes still give rise to the perception of transparency. Rather than seeing transparency as a perceptual end-point, determined by seemingly more primitive processes, we interpret perceived transparency as much a 'cause', as an 'effect'. We speculate that the anatomical substrate for such mutual interaction may lie in cortical feed-forward connections which maintain modular segregation and cortical feedback connections which do not. PMID- 2096369 TI - Preattentive vision and perceptual groups. AB - Recent evidence suggests that preattentive processing may not be limited to the analysis of simple stimulus features as previously suggested. To explore this idea a visual search task was used to test whether the shapes of several perceptual groups can be processed in parallel. Textured displays that give rise to strong perceptual grouping were used to create figures on a background. Search times for a target figure distinguished by a unique shape were found to be independent of the number of distractor figures in the display. This result indicates that perceptual groups may be processed in parallel and suggests an expanded role for preattentive processing in vision. PMID- 2096370 TI - Shape from shading in different frames of reference. AB - It has often been reported that, in the absence of information about the direction of illumination, people interpret surface convexities and concavities in accordance with the assumption that illumination comes from above. However, 'above' could mean with reference to gravity, the head or the retina. Yonas et al reported that four-year-old infants use the head more than gravity as the frame of reference in interpreting surface relief but that seven-year-olds make about equal use of the two frames of reference. The potency of these two frames of reference when acting separately and when pitted against each other was measured on adult subjects. For all subjects the 'assumption' about the direction of illumination was predominantly with respect to the head. The gravitational frame was used only when the headcentric frame was irrelevant, and then not consistently. PMID- 2096371 TI - Sensitivity to the displacement of facial features in negative and inverted images. AB - Subjects have previously been reported to show difficulties in recognising faces which are either inverted or in photographic negative. Experiments are reported in which a two-alternative forced-choice technique was used to measure sensitivity for distinguishing faces which have been modified by having the eyes moved vertically or horizontally. Subjects were less sensitive to such changes for inverted faces or negative faces, and were even less sensitive for faces that were both inverted and negative. No such effects were found for a control stimulus consisting simply of three solid circles in the same positions as the eyes and mouth of a face. When the stimuli consisted of eyes, nose, and mouth, but without a surround, no evidence of inversion or negation effects was found, which suggests that a facial surround is necessary. When the stimulus consisted of a facial surround with the eyes, nose, and mouth replaced by solid circles, effects of negation were found, but no effects of inversion. This dissociation of the effects of negation and inversion may suggest that they are the result of different underlying mechanisms. PMID- 2096372 TI - The rising fastball: baseball's impossible pitch. AB - Batters in professional baseball are confronted with pitches that appear to curve, dip, wobble, or rise. The rising fastball is a pitch where the ball appears to hop up as much as a third of a meter with a sudden increase in speed. Physics experiments confirm that many reported trajectories are possible, but not the rising fastball. The present paper shows how the apparent rise may be explained as a perceptual illusion due to the hitter underestimating original speed of the pitch. PMID- 2096373 TI - [Developmental phases and diagnostic criteria in diabetic nephropathy]. PMID- 2096374 TI - [Effect of chromatographic fractions of blood ultrafiltrates of patients with chronic uremia on the fibrinolytic activity]]. AB - Ultrafiltrates obtained from the patients with chronic uremia were chromatographically separated in the column filled with Sephadex A25. "Middle" molecular weight substances were localized mainly in a single peak. Dialysis decreased their contents. Determination of the fibrinolytic activity of each chromatographic fractions with caseinolytic and fibrinplate techniques has shown activating effect of the fractions 10-12. Dialysis decreased fibrinolytic activity statistically significantly. PMID- 2096375 TI - [Computer-assisted diagnosis of acute renal failure in children]. PMID- 2096376 TI - [Steroid-dependent nephrotic syndrome in children with IgA nephropathy]. AB - Nephrotic syndrome was diagnosed in 5 out of 14 children with IgA nephropathy. It was steroid responsive in two children. Clinical course of the disease was characterized by multiple recurrencies and variable response to steroid therapy. Periods of a complete sensitivity to prednisone were alternating with the periods of steroid-dependence, and resistance to steroids in on patient. Steroid sensitivity of the nephrotic syndrome in IgA nephropathy in childhood is rare. Therefore, the authors emphasize features of a positive prognostic value. PMID- 2096377 TI - [A case of renal failure in sarcoidosis]. PMID- 2096378 TI - [Etiopathogenesis of early stages of diabetic nephropathy]. PMID- 2096379 TI - [Nephrological complications after bone marrow transplantation]. PMID- 2096380 TI - [Is it worth to deal with the methods of editing of medical scientific publications?]. PMID- 2096381 TI - 5-Hydroxytryptamine receptor subtypes. AB - Significant advances in the molecular pharmacological analysis of 5 hydroxytryptamine (5-HT) receptor subtypes occurred in the 1980's. To a significant degree, this progress resulted from 2 independent approaches: molecular biology and molecular pharmacology. This review focuses on the pharmacological data derived from radioligand binding studies. At the present time, 5-HT receptor subtypes are often categorized into at least 3 major "families" as well as a few "orphan" receptors that cannot yet be placed into the major categories. Each "family" consists of multiple receptor subtypes which share similarities in their molecular biological, pharmacological, biochemical and physiological properties. In order to provide a comparative pharmacological analysis of the 7 most extensively characterized 5-HT receptor subtypes, potency information is presented on the 30 pharmacological agents that have been, to date, studied most extensively in the published literature. PMID- 2096382 TI - Exposure of rats to high concentrations of 1,1,1-trichloroethane and its effects on brain lipid and fatty acid composition. AB - Exposure of rats to 1,1,1-trichloroethane (TRI) (1200 p.p.m.) for 30 days resulted in changes in the fatty acid pattern of the brain ethanolamine phosphoglyceride. A decrease was observed in stearic acid (18:0) and arachidonic acid (20:4), while the 22-carbon (n-3) fatty acids were increased. These changes in the fatty acid pattern were similar to that observed previously in the rat for another solvent, perchloroethylene, at a lower exposure concentration (320 p.p.m). Both these solvents are little metabolised and it seems that a common mechanism exists whereby these solvents alter the fatty acid pattern of brain phospholipid upon exposure. The relatively low uptake of TRI makes a high exposure level (1200 p.p.m.) necessary to attain a blood concentration high enough for the changes to appear. PMID- 2096384 TI - Mechanisms behind the relaxing effect of furosemide on the isolated rabbit ear artery. AB - The effect of furosemide on isometric contraction and 86Rb uptake were studied in the isolated rabbit central ear artery (CEA). A concentration-dependent relaxing effect of furosemide (0.06 mM-1.0 mM) was found in vessel segments with intact endothelium. The maximal relaxation was 28.6 +/- 3.9% (10). The effect was not diminished in segments deprived of endothelium, and removal of endothelium itself caused no change of the force development to electrical field stimulation. The relaxing effect was time-dependent and stimulation-dependent and was not significantly affected by membrane depolarization induced by increasing external [K+] from 10 to 120 mM. The 86Rb uptake was inhibited by both furosemide and ouabain (8.0 +/- 0.5(8) and 5.3 +/- 0.5(8) versus 12.8 +/- 0.9(16) nmol (K+).mm 1.(10 min.)-1 in the furosemide (1.0 mM), ouabain (1.0 mM) and control groups, respectively) without interaction between the two drugs. The 86Rb uptake was not further inhibited by increasing the furosemide concentration from 0.12 mM to 1.0 mM. Our results suggest: firstly, the direct relaxing effect of furosemide on isolated vessel segments is endothelium-independent and secondly, the inhibition of the Na(+)-K(+)-Cl- cotransport and a possible consequent hyperpolarization of the membrane is unlikely to be the sole mechanism responsible for the vasorelaxant effect of furosemide. The demonstrated direct effect on vascular tone may be of clinical importance in situations with very high plasma concentrations of the drug or very low concentrations of serum albumin. PMID- 2096383 TI - Antidotal effect of lipopolysaccharide against acetaminophen-induced mortality in mice. AB - The possibility that pretreatment with LPS (lipopolysaccharide obtained from Escherichia coli), an immune system stimulant and interferon inducer, could prevent the hepatotoxic effects of acetaminophen (NAPAP) was investigated in mice. When mice were pretreated with LPS (4 mg/kg), intraperitoneally for 24 hr the mortality caused by NAPAP was considerably reduced. Histological examination of the livers and leakage of the enzymes into the blood demonstrated that NAPAP induced necrosis was decreased in LPS-treated mice compared to that induced by NAPAP alone. Pretreatment with 400 mg/kg or 800 mg/kg of NAPAP decreased the amount of covalently-bound acetaminophen metabolites. Since the level of hepatic glutathione and microsomal cytochrome P-450 were depressed in these experiments, it is concluded that LPS depresses the cytochrome P-450 species responsible for the formation of the toxic metabolites and that less reactive species are available for binding to cell macromolecules. PMID- 2096385 TI - Effect of sodium fluoride on growth of human diploid cells in culture. AB - Cytotoxicity of sodium fluoride (NaF) on human diploid cells in exponential growth was investigated using a) Flow 1000 cells, passage No. 13, obtained from skin and muscle tissues of male black foetus, b) IMR-90 cells, passage No. 22, derived from lung tissue of female Caucasian foetus and c) primary fibroblast like cell cultures from 5 Japanese whole foetuses. Diploid cells did not survive at 20 p.p.m. of ionic fluoride (F-) concentration. However, the cells were capable of proliferation with no significant impairment of growth up to 0.2 p.p.m. F-, a level which is much higher than the plasma concentration in human subjects from areas with highly fluoridated water. The growth of the cells was markedly affected by F- concentrations greater than 2 p.p.m. PMID- 2096386 TI - Mechanism of pharmacodynamic and pharmacokinetic interactions between acetohexamide and phenylbutazone in rabbits. AB - The interaction of acetohexamide (AH) with phenylbutazone (PBZ) was investigated in rabbits. Orally administered PBZ caused a potentiation of hypoglycaemic action after oral administration of AH. This can be explained by the fact that the co administration of PBZ significantly increased both the serum concentrations of AH and its pharmacologically active metabolite. (-)-hydroxyhexamide [(-)-HH], after AH administration. The co-administration of PBZ decreased the renal clearance (Clr) and non-renal clearance (Clnr) of AH. PBZ inhibited the in vitro reduction of AH to (-)-HH and decreased the accumulation of (-)-HH by the kidney cortical slices. These results indicate that the mechanism of in vivo interaction of AH with PBZ is complicated. PMID- 2096387 TI - Accumulation and distribution of aliphatic (n-nonane), aromatic (1,2,4 trimethylbenzene) and naphthenic (1,2,4-trimethylcyclohexane) hydrocarbons in the rat after repeated inhalation. AB - The concentrations of the C9 hydrocarbons n-nonane, 1,2,4-trimethylbenzene and 1,2,4-trimethylcyclohexane were measured in rat blood, brain and perirenal fat after exposures to 1000 p.p.m. of the individual compounds. Measurements were made by head space gas chromatography at the end of 12 hr exposures on days 1, 3, 7, 10 and 14 of the exposure periods. The relative concentrations of hydrocarbons in each organ were, brain: n-nonane "trimethylcyclohexane approximately trimethylbenzene, blood: trimethylbenzene "n-C9 greater than trimethylcyclohexane and perirenal fat: trimethylbenzene greater than n-nonane greater than trimethylcyclohexane, showing the widely different distribution properties of the different hydrocarbons. Brain/blood ratios of 11.4, 2.0 and 11.4, and fat/blood ratios of 113, 63 and 135 were found for n-nonane, trimethylbenzene and trimethylcyclohexane, respectively. A marked decrease in biological concentrations of trimethylbenzene and trimethylcyclohexane during the initial phase of exposure indicate that these hydrocarbons are capable of inducing their own metabolic conversion resulting in lower steady state levels. A special attention was made to n-nonane showing the highest concentration in brain concomitantly with a low blood concentration. This observation demonstrate that biological monitoring of occupational exposure by blood measurements not should be performed without knowledge of the distribution properties of the compounds investigated. PMID- 2096388 TI - The loss of glucoprivic feeding is an early-stage alteration in TCDD-treated Han/Wistar rats. PMID- 2096389 TI - Inactivation of hydrofluoric acid by solutions intended for gastric lavage. PMID- 2096390 TI - Clinical testing of prolonged action forms with special reference to extended release forms. CPMP Working Party on Efficacy of Medicinal Products. PMID- 2096391 TI - Evaluation of anticancer medicinal products in man. CPMP Working Party on Efficacy of Medicinal Products. PMID- 2096392 TI - Cocaine and body temperature in the rat: effects of exercise and age. AB - The laboratory rat is being used to determine if abuse of cocaine is a risk factor in the pathogenesis of exercise-induced heatstroke. The effect of running on a treadmill on the core temperature (Tc) has been studied in two groups of rats: animals approximately 20 weeks old ('young rats') and animals approximately 52 weeks old ('old rats'). During 60 min running the Tc increased to a steady level, within 15-30 min, which was higher in the old than in the young animals at environmental temperatures (Ta) of 25 and 30 degrees C. A significantly greater rise occurred in both groups of animals at Ta of 30 compared to 25 degrees C. Injection of cocaine (20 mg/kg) was without effect on the rise in Tc in young animals running at a Ta of 25 degrees C but significantly increased the hyperthermia in the old rats. It is suggested that the rise in the thermoregulatory set point induced by muscle exercise is greater with advancing age. Also in older animals, the effect of cocaine on the central nervous system may be enhanced. PMID- 2096393 TI - Lack of tolerance to imipramine or mianserine in two animal models of depression. AB - Few clinical reports describe tolerance induced by antidepressants and this question is considered an unsolved problem for clinical use of this group of drugs. The present report deals with the effects of imipramine and mianserine on two animal models of depression, after acute or prolonged previous treatment with these antidepressants. Imipramine and mianserine potentiated amphetamine-induced anorexia both after acute administration or after prolonged previous treatment with each drug. Mianserine effects were not detected in the behavioral despair test and imipramine reduced rats immobility equally after acute and prolonged previous treatment. It was concluded that imipramine and mianserine do not induce detectable tolerance when previously administered to animals submitted to amphetamine anorexia or behavioral despair. PMID- 2096395 TI - Effect of the new zinc compound beta-alanyl-L-histidinato zinc on bone metabolism in elderly rats. AB - The effect of a new zinc compound beta-alanyl-L-histidinato zinc (AHZ) on bone metabolism was investigated in aged rats (30 weeks old). AHZ (1.0, 2.5 and 7.5 mg/100 g body weight) was orally administered to rats 3 times at 24-hour intervals, and the rats were bled 24 h after the last administration. The administration of AHZ (7.5 mg/100 g) did not cause an appreciable alteration of calcium and inorganic phosphorus concentrations in the serum, and zinc, calcium and deoxyribonucleic acid contents in the femoral diaphysis were significantly increased by the administration of AHZ (7.5 mg/100 g). The bone alkaline phosphatase activity was significantly increased by doses of 1.0-7.5 mg AHZ/100 g. These results suggest that AHZ has a stimulatory effect on bone formation and calcification in aged rats. PMID- 2096394 TI - Beta-alanyl-L-histidinato zinc prevents the toxic effect of aluminium on bone metabolism in weanling rats. AB - The preventive effect of beta-alanyl-L-histidinato zinc (AHZ) on the toxic action of aluminium on bone metabolism was investigated in the femoral diaphysis of weanling rats. Aluminium chloride (5.0, 10.0 and 20.0 mumol A1/100 g body weight) was orally administered for 3 days. The dose of 10.0 and 20.0 mumol A1/100 g caused a significant increase in serum calcium concentration and bone acid phosphatase activity, while bone alkaline phosphatase activity and calcium content were not altered significantly. Moreover, the bone DNA content was significantly decreased by the doses of 10.0 and 20.0 mumol A1/100 g. Meanwhile, the increase in serum calcium concentration caused by the administration of aluminium (20 mumol/100 g) was completely prevented by the simultaneous administration of AHZ (1.0 and 2.5 mg/100 g) for 3 days, although AHZ alone did not have any effect. Also, the effects of aluminium (20.0 mumol/100 g) to increase bone acid phosphatase activity and to decrease the bone DNA content were completely blocked by the simultaneous administration of AHZ (1.0 and 2.5 mg/100 g). AHZ (1.0 and 2.5 mg/100 g) alone had the effect to increase bone DNA content but not bone acid phosphatase activity. The present study indicates that AHZ can prevent the revelation of the toxic effect of aluminium on bone metabolism in rats. PMID- 2096396 TI - Antitumour activities of copper-ATP complex on transplantable murine lymphoma. AB - A synthetic metal-nucleotide complex [Cu3(ATP)26H2O]2- has been found to have a significant tumour inhibitory effect on Dalton's lymphoma. Moreover, the haematopoietic system of the treated hosts is favourably disposed and the life span is much increased. It is noteworthy that the tumour inhibitory effect is enhanced by combination therapy. PMID- 2096397 TI - Plasmid transformation of Bacteroides spp. by electroporation. AB - Transformation of Bacteroides spp. with a variety of plasmid DNAs was accomplished using electroporation. The standard transformation assay system used to deduce the optimal electroporation parameters employed a 50-to 100-fold concentrated cell suspension of mid-logarithmic phase Bacteroides fragilis strain 638 and the 5.4-kb clindamycin resistance (Ccr) vector, pBI191. A variety of electroporation buffers were used successfully in transformation experiments but of these, 1 mM MgCl2 in 10% glycerol was superior. The incorporation of MgCl2 was essential for optimum viability prior to electroporation and for optimum transformation. Transformants were routinely obtained using 5-ms pulses over a range of field strengths from 5 to 12.5 kV/cm, with a maximum of greater than 10(6) micrograms-1 DNA at 12.5 kV/cm. The number of transformants increased linearly with respect to DNA concentration over the range 0.01-2 micrograms tested. Recovery of transformants required an expression period of up to 2.5 h following exposure to the electric field. This period, however, was dependent on the antibiotic resistance marker used for selection of transformants, with a significantly shorter incubation required when chloramphenicol rather than clindamycin was used in the selective medium. The effect of the DNA source on transformation was tested using the shuttle vector pFD288. Plasmid DNA isolated from Bacteroides uniformis, Bacteroides ovatus, or Bacteroides thetaiotaomicron transformed B. fragilis 638 at frequencies 7.5- to 12.5-fold less than those observed for controls with homologous DNA. Further reductions were seen with Escherichia coli purified pFD288, which transformed at 1000-fold lower frequencies. Finally, using homologous pFD288 or pBI191 isolated from strain 638, several strains of B. fragilis, B. uniformis, and B. ovatus were transformed successfully without modification of the standard assay system. Two strains each of B. thetaiotaomicron and Bacteroides ruminicola were not transformed using the methods described here. PMID- 2096398 TI - The sequences of genes bordering oriT in the enterotoxin plasmid P307: comparison with the sequences of plasmids F and R1. AB - The nucleotide sequences of the enterotoxin plasmid P307 transfer genes traM, finP, traJ, traY, and gene 19 were determined. Gene 19 is highly conserved; its product is very similar to that coded by the F and R1 plasmids. The TraM protein is similar in P307 and in F; the R1 sequence shows differences in the 40 N terminal amino acids. The traJ product is very different in P307, F, and R1. The traY gene from P307, which in F is almost twice as long, is similar in size to that from R1. The finP RNA shows a high degree of homology with that from R1 and F, except for the two loop regions where base changes were observed. The genes coding for proteins, except traY, could be expressed in minicell- and T7 promoter driven expression systems, whereas traJ and gene 19 could be expressed only in the latter system. PMID- 2096399 TI - Amplification on the Amycolatopsis (Nocardia) mediterranei plasmid pMEA100: sequence similarities to actinomycete att sites. AB - An amplification of a 2.0-kb fragment was found on the plasmid pMEA100 isolated from a subculture of the wild-type strain LBG A3136 of Amycolatopsis (Nocardia) mediterranei. Plasmid preparations contained a mixture of molecules with copy numbers of the amplified unit in the range of 2 to 10. The amplification on pMEA100 was stable; propagation of cells for many generations did not change the pattern of the amplified DNA. Fragments of the plasmids containing the amplifiable unit of DNA (AUD) and the amplified DNA sequence (ADS) were subcloned and characterized. Sequencing of the AUD terminal regions and the junction between ADS units showed that the amplifiable unit of DNA was flanked by 12-bp direct repeats. The DNA segments adjacent to the 12-bp sequence common to the left and right AUD terminal regions also showed significant similarities. In addition, the left AUD terminal region flanking the 12-bp repeat exhibited considerable sequence similarity to actinomycete plasmid attachment sites, particularly to the pMEA 100 att site. PMID- 2096400 TI - High-level expression vectors for Caulobacter crescentus incorporating the transcription/translation initiation regions of the paracrystalline surface-layer protein gene. AB - A number of plasmid vectors were constructed for high-level gene expression in the dimorphic gram-negative bacterium Caulobacter crescentus. These vectors incorporate the transcription and translation initiation regions of the C. crescentus CB15A rsaA gene, which codes for the abundantly synthesized protein comprising the bacterium's paracrystalline surface layer. The expression vectors are based on the broad-host-range IncQ plasmid RSF1010 (R300B) and incorporate the rsaA promoter and transcription start site. Some vectors also contain translation initiation information; these can result in the addition of as little as a single glycine residue to the protein encoded by the cloned segment. The vectors can be introduced into C. crescentus by electroporation at high frequency (ranging up to 10(6)-10(7) electroporants/micrograms DNA with surface-layer deficient mutant C. crescentus CB2A) or conjugal transfer. They range in size from 10 to 12 kb, specify either chloramphenicol or kanamycin resistance, and possess the restriction sites EcoRI, BamHI, KpnI, and SstI for cloning genes downstream of the rsaA gene sequences. For a number of the vectors, the complete nucleotide sequence is known. A comparison was made between the expression of an endoglucanase gene from these plasmids in C. crescentus CB2A and CB15A and similar constructions under the control of lacZ alpha transcription and translation initiation signals carried on a pUC9 vector in an Escherichia coli host. The two expression systems compared favorably; cell lysates prepared from C. crescentus CB2A exhibited 40% of the endoglucanase activity of similarly prepared lysates from E. coli JM101. Lysates prepared from C. crescentus CB15A exhibited only 8% of the endoglucanase activity of E. coli lysates. PMID- 2096401 TI - Isolation of a second cryptic plasmid from Mycoplasma mycoides subsp. mycoides. AB - Plasmids have rarely been detected in organisms constituting the genus Mycoplasma. Recently, the isolation of a cryptic plasmid from Mycoplasma mycoides subsp. mycoides has been described, and we report here the isolation of a second cryptic plasmid from this species. Restriction map and Southern blot analyses show that the second plasmid is distinct from the previously described plasmid, although a limited region of homology was detected. The availability of mycoplasmal cryptic plasmids may lead to the development of cloning vectors that replicate in these organisms. PMID- 2096402 TI - Chloramphenicol acetyltransferase expression in marine Rhodobacter sp. NKPB 0021 by use of shuttle vectors containing the minimal replicon of an endogenous plasmid. AB - A vector, pUK318, was constructed to allow the expression of foreign genes in the marine photosynthetic bacterium Rhodobacter sp. NKPB 0021. This strain has been cured of its two endogenous plasmids. pUK318 consists of a 2.3-kb PstI-BamHI restriction fragment, containing a marine Rhodobacter plasmid replication region, cloned into pUC18. This fragment was derived from plasmid pRD31, a 3.1-kb endogenous plasmid purified from the marine strain Rhodobacter sp. NKPB 043402. A kanamycin resistance gene from Tn903 was cloned into the PstI restriction site to provide antibiotic selection. pUK318 was transferred to Rhodobacter sp. NKPB 0021 by transformation, and efficiencies of 7.2 x 10(-5) were obtained. Furthermore, pUK318 was stably maintained when transformants were grown either heterotrophically or photosynthetically in the absence of antibiotics. pUK318 was used to express the Escherichia coli chloramphenicol acetyl transferase (CAT) gene in Rb. NKPB 0021. Transformants expressed a maximum CAT activity of 1.12 mmol/min/g dry cells. In addition, the DNA region essential for pUK318 replication in Rb. NKPB 0021 was localized to a 1.36-kb HincII-PstI fragment. This is the first report of a plasmid vector containing a marine Rhodobacter specific replicon that allows stable expression of foreign genes in the absence of antibiotic selection. PMID- 2096403 TI - Drug interactions in the reinforcing effects of over-the-counter cough syrups. AB - Drug interactions in reinforcin effects of over-the-counter cough syrups were investigated by utilizing place preference conditioning in rats. Dihydrocodeine (2 mg/kg, IP) induced a small, non-significant place preference. On the other hand, concurrent dosing of dihydrocodeine (2 mg/kg, IP) and a mixture (SC) of methylephedrine (4 mg/kg), caffeine (4 mg/kg) and chlorpheniramine (0.8 mg/kg) produced a significant place preference, the mean conditioning score in this group being about 3 times higher than that in the dihydrocodeine alone group. The potentiation of dihydrocodeine-conditioned place preference was observed by combination with chlorpheniramine (0.8 mg/kg, SC) alone as well as with the mixture, but neither with methylephedrine (4 mg/kg, SC) nor with caffeine (4 mg/kg, SC). Chronic infusion of the dopamine D1 receptor antagonist SCH23390 (1.0 mg/kg/day, SC) during conditioning abolished the appetitive effects of dihydrocodeine combined with chlorpheniramine. In conclusion, it is suggested that the potentiation of appetitive effects of dihydrocodeine is mostly due to chlorpheniramine among three ingredients in the cough syrups, and that the dopaminergic system, especially D1 receptor, may play an important role in the potentiation effect of chlorpheniramine on the reinforcing effects of dihydrocodeine. PMID- 2096404 TI - Cocaine-base smoking in rhesus monkeys: reinforcing and physiological effects. AB - Four rhesus monkeys were trained to smoke cocaine-base under a progressive ratio (PR) schedule, with ten smoking trials available each day. Unit dose was varied from 0.25 to 3 mg/kg, and lidocaine (2 mg/kg) was substituted for cocaine. Number of responses and break-point on the PR schedule increased with dose while the number of smoke deliveries increased only slightly. Maximum daily smoke deliveries ranged from six to nine across monkeys. When lidocaine (2 mg/kg) was substituted for cocaine-base, responding decreased to approximately half of that maintained by cocaine, and when cocaine was reinstated, higher response rates returned. Cardiovascular changes associated with cocaine smoking were monitored with an indwelling radio transmitter. There was an initial decrease in heart rate (30 s) followed by a rapid rise and decline by the end of the 15-min trials. Blood pressure increased rapidly after trial onset and returned to pretrial baseline by 15 min. Over the eight trials completed during a session, heart rate and blood pressure steadily increased over presession base-lines during the first four trials, but there was then a decline suggesting acute tolerance development. Observations of the monkeys after each trial revealed dilated pupils and slightly agitated, hyperactive behavior. These findings indicated that smoked cocaine-base was rapidly established as a reinforcer for monkeys, and the physiological effects were similar to those reported in studies of human subjects. PMID- 2096405 TI - Effects of intranasal cocaine on human learning, performance and physiology. AB - The behavioral and physiological effects of intranasally administered cocaine (placebo, 48, 96 mg/70 kg) were examined in eight recreational cocaine users under controlled laboratory conditions. The 48 and 96 mg doses of cocaine significantly improved subjects' performance on the Digit Symbol Substitution Test above levels observed either prior to drug administration or when placebo was administered. These effects were discernible for up to 120 min after cocaine administration. Cocaine had no statistically significant effects on learning and performance of ten-response sequences. The 48 and 96 mg doses increased heart rate and blood pressure for up to 180 min, and increased subject ratings of drug effects and decreased skin temperature for 60-90 min after drug administration. Cocaine produced no significant effects on the electrocardiogram. To our knowledge, this is the first experimental demonstration that acutely administered cocaine can improve behavioral performance in rested subjects. In addition, the duration of cardiac effects in this study was longer than previously reported with intranasal cocaine, perhaps due to the concurrent behavioral testing. PMID- 2096406 TI - Serenics fluprazine (DU 27716) and eltoprazine (DU 28853) enhance neophobic and emotional behaviour in mice. AB - Two tests designed to elicit responses to novelty and to aversive stimuli were used to study the effects of the serenics fluprazine and eltoprazine on the behaviour of male Swiss mice: a free exploratory test (fluprazine; 2.5, 5 and 10 mg/kg; eltoprazine: 2.5, 5, 10 and 15 mg/kg) and a two-box choice procedure (fluprazine: 1.25, 2.5, 5 and 7.5 mg/kg; eltoprazine: 2.5, 5, 7.5 and 10 mg/kg). Both drugs increased the neophobic reaction, as well as the avoidance of a brightly illuminated box. These effects closely resemble those of psychostimulant drugs such as methamphetamine and caffeine. It is hypothesized that the behavioural changes induced by these drugs may be due to a nonspecific increase of the emotional reactivity of animals. PMID- 2096407 TI - Desipramine and restraint stress induce odor conditioned aversion in rats: suppression by repeated conditioning. AB - Rats exposed to one, three, or seven conditioning sessions defined by an olfactory conditioned stimulus and stress or antidepressant administration as unconditioned stimulus were later tested for their preference for the conditioned olfactory stimulus. A significant reduction of the time spent in the conditioned stimulus was observed in animals exposed to one and three pairings with stress or three pairings with desipramine. A lack of conditioned aversion was observed in animals exposed to seven pairings with either reinforcer. These data could indicate that the adaptative mechanisms elicited by repeated stress or desipramine may be involved in the decrease of conditioned aversion. PMID- 2096408 TI - Reduced haloperidol plasma concentration and clinical response in acute exacerbations of schizophrenia. AB - Twenty-nine hospitalized patients suffering acute exacerbations of schizophrenia were treated for 2 weeks with fixed daily oral doses of haloperidol prospectively calculated to achieve a haloperidol plasma concentration of either 8-18 ng/ml or 25-35 ng/ml. Reduced haloperidol as well as haloperidol concentrations were assayed to determine if the former enhanced the predictability of response. Wee 2 haloperidol plasma concentrations were negatively correlated to clinical response as measured by the percentage change in the BPRS score from baseline (r = -0.43, P less than 0.05). In contrast, week 2 plasma concentrations of reduced haloperidol, total haloperidol (haloperidol + reduced haloperidol), and reduced haloperidol/haloperidol ratio did not correlate with the change in the BPRS score. Chi-square analysis concluded that patients with ratios greater than one were no less likely to be treatment responders (less than 25% improvement in BPRS from baseline and week 2 BPRS less than 55) than those with ratios less than one. Although these data lend additional support to reports of a curvilinear relationship between haloperidol plasma concentration and clinical response, they also suggest that reduced haloperidol plasma concentrations are of no value in predicting treatment response. PMID- 2096409 TI - Behavioural effects of the nicotinic agonists N-(3-pyridylmethyl)pyrrolidine and isoarecolone in rats. AB - The nicotinic agonists N-(3-pyridylmethyl)pyrrolidine (PMP) and isoarecolone have been compared with (-)-nicotine in three behavioural procedures and as inhibitors of [3H]-(-)-nicotine binding. Locomotor activity was recorded as movements between beams of infra-red light (ambulation). In experimentally naive rats, nicotine, PMP and isoarecolone reduced ambulation. In rats receiving nicotine chronically and previously exposed to the activity cages, nicotine and PMP increased ambulation in a dose-related manner. However, isoarecolone did not increase ambulation at doses that were active in other procedures. In rats trained to discriminate nicotine from saline in a two-bar operant conditioning procedure with food reinforcement, there was full generalization to PMP. It was also found that PMP potently inhibited the binding of [3H]-(-)-nicotine to rat brain membranes in vitro. These results were discussed with previous data for the discriminative stimulus and ligand-binding effects of isoarecolone obtained under similar conditions. The relative potency of PMP in different behavioural procedures was similar to that of (-)-nicotine. However, isoarecolone was relatively 10 times more potent in decreasing ambulation than would have been expected from its potency in the ligand-binding and discriminative stimulus procedures. The results suggest that the pharmacodynamic action of isoarecolone differs from that of nicotine and PMP, and that it will be a useful probe in further analyses of central nicotinic mechanisms. PMID- 2096410 TI - Lateral striatal cholinergic mechanisms involved in oral motor activities in the rat. AB - These experiments were undertaken to determine if local injection of pilocarpine in the neostriatum of the rat produces oral motor activities that are similar to those produced by systemic administration. In the first experiment, IP administration of 2.0-8.0 mg/kg pilocarpine increased chewing movements and tongue protrusions. In the second experiment, chronic guide cannulae were implanted bilaterally in ventromedial or ventrolateral striatum, and rats were injected with saline, 30, and 60 micrograms pilocarpine (per side). A dose related increase in vacuous chewing was induced by injections of pilocarpine in the ventrolateral but not the ventromedial striatum. Tongue protrusions were induced by injections of pilocarpine into the ventromedial and the ventrolateral striatum. A third experiment demonstrated that this response was blocked completely by 10 micrograms scopolamine co-administered via the same cannulae, but the response was not reduced significantly by 10 micrograms haloperidol. These results indicate that ventrolateral striatal cholinergic mechanisms are involved in oral motor activities in the rat. This syndrome may provide a model for human clinical phenomena such as parkinsonian tremor. PMID- 2096413 TI - Selenium supplementation improves mood in a double-blind crossover trial. AB - The possibility that a sub-clinical deficiency of the trace element selenium might exist in a sample of the British population was examined by giving a selenium supplemented for 5 weeks. Using a double-blind crossover design 50 subjects received either a placebo or 100 micrograms selenium on a daily basis. On three occasions they filled in the Profile of Moods state. Mood did not change when taking the placebo, whereas when taking the selenium the subjects reported a substantial improvement after both 2.5 and 5 weeks. PMID- 2096412 TI - Brain 5-HT1 binding sites in depressed suicides. AB - 5-HT1 and 5-HT1A binding sites were measured in brain tissue obtained at postmortem from 19 suicides, with definite evidence of depression, and 19 sex and age-matched controls. Thirteen of the depressed suicides had not been prescribed psychoactive drugs recently (drug-free suicides); six had been receiving antidepressant drugs, alone or in combination with other drugs (antidepressant treated suicides). No significant differences were found in the number or affinity of 5-HT1 and 5-HT1A binding sites in frontal or temporal cortex between drug-free suicides and controls. The number of 5-HT1 sites was significantly lower (by 20%), affinity unaltered, in hippocampus and the affinity significantly lower (by 33%), number unaltered, in amygdala of drug-free suicides than controls. The number of 5-HT1 binding sites tended to be higher and the affinity lower in the antidepressant-treated compared to drug-free suicides, and significantly so in hippocampus. The present results, together with our previous studies, provide no evidence of altered cortical 5-HT markers in depressed suicides, but further emphasise abnormalities in the hippocampus. PMID- 2096411 TI - Comparison of the effects of Alzheimer's disease, normal aging and scopolamine on human transient visual evoked potentials. AB - Transient visual evoked potentials elicited by the onset of a patterned stimulus were recorded in patients suffering from Alzheimer's disease (AD), in healthy elderly controls and in healthy young individual. The latencies and amplitudes of both the components studied were adversely affected by normal aging and one of the components, CI, but not the other, CII, showed further deterioration in AD. These changes occurred over a range of stimulus contrast levels. The changes found in AD, but not those seen in normal aging, could be mimicked by administration of the cholinergic antagonist scopolamine to young volunteers. PMID- 2096414 TI - Self-inhibiting action of nortriptyline's anti-immobility effect at high plasma and brain levels in mice. AB - Animals were treated acutely with 0, 2.5, 5, 10, 20 and 40 mg/kg nortriptyline (NT) 30 min before the tail suspension test (TST). They were sacrificed after test for evaluation of plasma and brain levels of NT. The anti-immobility effect increased with increasing doses and concentrations of the drug, reaching statistical significance (P less than 0.01, Dunnett test) at a dose of 20 mg/kg, 865 ng/ml in plasma and 11 micrograms/g in brain tissue. The anti-immobility effect was, however, blocked with the highest, non-toxic, concentrations. Results seem to indicate a biphasic curvilinear relationship between plasma and brain levels of NT and behaviour in mice. PMID- 2096415 TI - Discrimination of an amphetamine-pentobarbitone mixture by rats in an AND-OR paradigm. AB - Rats were trained to discriminate a mixture of amphetamine plus pentobarbitone from either drug separately in a two-bar procedure with food reinforcement. Discrimination was 86% accurate after 48 sessions, and no dose of amphetamine or pentobarbitone alone produced mixture-appropriate responding. Some mixtures increased response rates whereas the same doses of each drug separately had little effect. The same rats were then trained to discriminate a mixture from saline. There was a continuing lack of discriminative response to amphetamine and only a partial response to pentobarbitone, and under these conditions mixtures did not increase overall response rates. Thus, the way rats are trained, and their previous history, can determine the characteristics of the cue obtained. PMID- 2096417 TI - [Multiple sclerosis: review of main experimental data and pathogenic hypotheses]. AB - The pathogenesis of multiple sclerosis (MS) is considered from three different viewpoints: genetic, viral and immunological. A genetic predisposition intervenes, as testified by the familial forms of MS and by the frequency of HLA A3B7 and DR2 groups in MS patients. The hypothesis of an inherited enzyme deficiency in oligodendrocytes is discussed. Many viruses are known to induce demyelination in animals, and the intrathecal production of antibodies to measles virus as well as the in vitro discovery of DNA transcripts of this virus in patients are suggestive of a viral factor. Experimental allergic encephalomyelitis (EAE) and chronic EAE have made it possible to study the immune and other mechanisms which might be involved in MS. While the myelin basic protein and the M2 antigen appear to be the first antigen targets, the demyelinating agents in this model are antibodies to galactocerebroside. The factors responsible for demyelination in MS have not yet been elucidated, but the antibodies present in the cerebrospinal fluid do not seem to be demyelinating in vitro. Descriptions of the cells which constitute the lesions and of the antigen markers they express suggest that endothelial cells and astrocytes (possibly presenting antigens to lymphocytes) might play a part in the genesis of the lesions. Experiments concerning the modulation and suppression of EAE allow new therapeutic approaches to be envisaged. PMID- 2096418 TI - [Anti-aggregants in 1990]. AB - Antiplatelet drugs are increasingly used in the prevention of arterial thrombosis. Aspirin in doses of circa 300 mg day may be recommended for the primary prevention of myocardial infarction, but only in subjects at moderate to high risk of cardiovascular disease. Antiplatelet agents are useless in stable angina, but aspirin reduced by about 50% the risk of myocardial infarction and the overall mortality rate among patients with unstable angina. A lower dose of aspirin (150 mg/day) also reduces mortality by 23% in the acute phase of myocardial infarction. In doses of 300 mg/day, aspirin is useful in the secondary prevention of myocardial infarction and reduces the overall mortality rate by 15%. Various antiplatelet agents, including aspirin (alone or combined with dipyridamole) and ticlopidine, have proved useful to avoid thrombosis in aorto coronary grafts, provided treatment begins at the latest 6 hours after surgery. The usefulness of antiplatelets has been well established in the prevention of immediate reocclusion following coronary angioplasty, but not in the prevention of late reocclusion. Aspirin and ticlopidine are useful in the extracorporeal circulation techniques. In patients with cardiac valve prosthesis, antivitamin K anticoagulants are still indispensable, but their antithrombotic effect can be reinforced by dipyridamole or aspirin. Diuretics probably provide the best primary protection against cerebrovascular accidents, although medium doses of aspirin may be considered in elderly people at high risk of such accidents. Aspirin (alone or combined with dipyridamole) and ticlopidine may be recommended for the secondary prevention of cerebral ischaemic accidents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096416 TI - [Aspects of pneumocystosis seen in a French pneumonology department in 1987 1988]. AB - Over a 2 years' period, 49 AIDS patients and 3 non AIDS patients were treated for pneumocystosis in our chest department. Forty-six were male and 6 were female. Pneumocystosis was the first opportunistic infection in 77 p 100 of patients. Fever above 38.5 degrees C was the major symptom in 92 p 100. Cough was present in 90 p 100 and dyspnoea in 94 p 100. Clinical symptoms had begun 21.7 +/- 15.7 days before diagnosis. Mean PaO2 value was 50.9 +/- 15.7 mmHg. Forty-eight patients were initially treated by daily intravenous administration of trimethoprim 960 mg and sulfamethoxazole 4,800 mg. Three patients received a pentamidine aerosol and one received DFMO. Treatment was effective in 39 patients; 11 patients died between the 5th and the 29th days of treatment; 2 had an early relapse. Fever disappeared after 9.8 +/- 6.6 days, and blood gases returned to normal within 10.8 +/- 7.7 days. All patients whose PaO2 was above 56 mmHg were cured. Thus, the trimethoprim-sulfamethoxazole combination proved active in the treatment of pneumocystosis. Other treatments are useful in case of side-effects or failure of the initial therapy. Failures can be suspected on the fourth day of treatment and in such cases CMV co-infection must be looked for and treated. PMID- 2096419 TI - [Oncogenes, anti-oncogenes and their alterations in human tumors]. AB - This review summarizes the discovery of oncogenes which are the activated versions of normal cellular protooncogenes which serve essential functions in the control of cell proliferation and differentiation. Their activation disrupts the normal control mechanism which rests on the subtle balance between their effects and those of anti-oncogenes or tumor suppressor genes. One may reasonably hope that defining a complete profile of alterations of both these types of essential genes in the tumor or in the clinically healthy individual will be invaluable to assess prognosis or genetic predisposition, respectively. PMID- 2096420 TI - [Infectious esophagitis in HIV infection]. AB - Infectious oesophagitis is the most frequent of digestive tract diseases occurring in patients with AIDS. It is diagnosed by endoscopy which permits brushing and biopsy of mucosal lesions for cytological, histological and microbiological examinations. In 40 to 50 percent of HIV positive patients, Candida is responsible for oesophagitis which is often asymptomatic and almost regularly associated with oral candidiasis. Brushing is preferable to biopsy to confirm a diagnosis which is frequently obvious at endoscopy. The prevalence of CMV and HSV oesophagitis has perhaps been underestimated. Diagnosis rests on the finding of intranuclear inclusions, usually in endothelial cells of the chorion for CMV and in epithelial cells for HSV. The demonstration of viral antigens by immunoperoxidase staining is useful in difficult cases, as is viral culture. Antiviral agents (gancyclovir against CMV, acyclovir against HSV) are usually effective. Co-infection with both Candida and a virus is not uncommon. The other pathogens, such as bacteria or mycobacteria, are exceptional. The authors suggest a therapeutic strategy taking into account epidemiological and clinical data. PMID- 2096421 TI - [Sternal site of sarcoidosis]. AB - Sarcoidosis is seldom revealed by bone lesions since these are almost exclusively seen in the chronic forms of an already diagnosed disease. We report a case of sarcoidosis where sternal lesions were the first to appear. The diagnosis was suggested by radiological findings and confirmed by the presence of other manifestations of sarcoidosis, notably lymph node involvement. Pain and functional impairment were such that we had recourse to corticosteroid therapy. PMID- 2096422 TI - [Acute and reversible interstitial granulomatous nephropathy after treatment with captopril]. AB - Angiotensin-converting enzyme inhibitors (CEI) have been found effective in numerous cases of arterial hypertension, even non renovascular, and they are now widely used. However, the reference compound, captopril, has exhibited various side-effects, including acute renal failure. Different mechanisms may be responsible for this complication. In some case haemodynamic changes occur which are rapidly reversible after treatment is discontinued. In other, less frequent cases, captopril induces an immunoallergic interstitial nephritis, sometimes accompanied by skin rashes and/or eosinophilia. Since renal biopsies have been performed in only a few cases of CEI-induced nephropathy, we thought that it might be of interest to report a case of acute renal failure due to acute interstitial nephritis with epithelioid granulomas in the interstitium. The favourable outcome was confirmed by two successive follow-up renal biopsies. PMID- 2096423 TI - [Anemia caused by iron deficiency and pagophagia. Apropos of a case]. AB - The authors report a case of a 17 year old young man, who entered our hospital for a severe iron lack anemia reported to ice cubes ingestion (Pagophagia). Such cases are reported in the literature. Usually, Pagophagia is a compulsive eating (Pica) caused by iron deficiency. Pagophagia could improve non hematologic symptoms of iron deficiency such as stomatitis and glossitis. PMID- 2096424 TI - [Generalized status epilepticus after ingestion of ibuprofen (Brufen), disclosing systemic lupus erythematosus]. AB - We report a case of aseptic meningoencephalitis induced by ibuprofen (Brufen) in a 24-year old unmarried woman with unrecognized systemic lupus erythematosus. The neurological manifestations induced by ibuprofen revealed the systemic disease. Clinicians confronted with aseptic meningitis or meningoencephalitis developed after treatment with a non-steroidal anti-inflammatory drug, notably ibuprofen, should investigate for systemic disease. PMID- 2096426 TI - [Efficacy of azidothymidine in thrombopenia associated with HIV infection]. AB - We report an observation where a patient suffering HIV related thrombocytopenia was followed up for 23 months. Introduction or reintroduction of azidothymidine obtained a raise of platelet rate. When azidothymidine was stopped, platelet rate climbed down. This observation is in agreement with recent data suggesting efficiency of azidothymidine on HIV related thrombocytopenia. PMID- 2096425 TI - [Adrenal adenoma disclosing after delivery]. AB - Pregnancy and Cushing's syndrome are seldom found together (40 cases in the literature), since hyperadrenocorticism is often responsible for anovulation by gonadotropin suppression. We report the case of a 25-year old para II woman whose pregnancy was complicated by diabetes and arterial hypertension at 31 weeks and who received the conventional treatments (special diet, insulin therapy, pindolol). Caesarean section, motivated by premature rupture of the membranes, was performed at 37 weeks, delivering a healthy infant. The diagnosis of hypercortisolism with low ACTH level was made post partum. An adrenal tumour (the most frequent cause of Cushing's syndrome occurring during pregnancy) was removed after pre-operative treatment with ketoconazole, and endocrine functions returned to normal. PMID- 2096427 TI - [Visceral leishmaniasis of favourable course in a patient with renal transplantation]. AB - The authors report a case of non fatal visceral leishmaniasis in a renal transplant recipient and underline the fact that immunosuppressive treatments facilitate the occurrence of this disease. In patients with fever, pancytopenia and spleen enlargement, it is capital to inquire whether they have sojourned in a country where leishmaniasis is endemic. The diagnosis is then confirmed by bone marrow examination. Treatment rests on antimony derivatives, but these must be handled with caution in immunocompromised patients. PMID- 2096428 TI - [Association of sarcoidosis and primary biliary cirrhosis: review of the literature apropos of a new case]. AB - We report a case of sarcoidosis associated with primary biliary cirrhosis in a 56 year old woman, with a 5 years' follow up. Sarcoidosis was ascertained by chest X ray, gallium scintigraphy, broncho-alveolar washing and liver biopsy (intralobular epithelioid granulomas). The diagnosis of primary biliary cirrhosis was based on IgM level increase (4 g/l), AMA positivity (1/1000) and liver biopsy assessment (non suppurative chronic cholangitis). Such an association is rare (12 detailed cases in literature), brings out pathophysiological questions and points to an additional mechanism of cholestasis in patients with sarcoidosis. PMID- 2096429 TI - [Realization of an assisted system for medical decision and follow-up in hematologic diseases treated with sequential chemotherapy]. AB - The follow-up of patients treated with sequential chemotherapy in internal medicine departments with special interest in haematology imposes a heavy burden on the entire treating staff. The chances of errors, notably in medical prescriptions and care, are not negligible, and these errors result in iatrogenic complications, readmissions and prolonged stays in hospitals. Designing a medical decision and therapeutic follow-up aid system should be time-saving for the staff and ensure good quality and safe prescriptions as well as reliable therapeutic evaluations and better hospital management. The system described here is developed on 4D Macintosh computer which handles a relational data-base. It includes the data-base, i.e. a knowledge-based system devised by the expert clinician containing "declarative" data and deduced rules which represent the expert's reasoning and determine the action to be taken, and the interface between them. The system easily accepts many parameters, thereby enabling medical knowledge and therapeutic attitudes to be updated. PMID- 2096430 TI - [Familial hypobetalipoproteinemia. Familial study of 4 cases]. AB - A familial study of four cases with hypobetalipoproteinemia is reported. Three members are heterozygous and one is homozygous. This congenital fat malabsorption in homozygous state is commonly associated with an absence of serum apoprotein B and LDL. Neuromuscular and ophthalmological signs are absent in this case. The major role of upper digestive endoscopy in the diagnostic procedure is emphasized. Histochemical and immunoenzymatic stains of enterocytes and intestinal organ culture show defective synthesis apo B in the homozygous patient. Studies of DNA polymorphism in the homozygous patient have shown that the apo B gene doesn't certain major insertions or deletions. These results are discussed. PMID- 2096431 TI - [Coccygodynia disclosing Tarlov's cysts]. AB - In a 63-year old male patient coccygodynia, initially isolated then complicated by incomplete cauda equina syndrome, could be attributed to large perineurel meningeal cysts on the sacral nerve roots. The diagnosis was suspected at computerized tomography and nuclear magnetic resonance and confirmed by sacculoradiculography. Intradural injections of corticosteroids provided lasting pain relief. Arachnoid cysts are often asymptomatic, by they may be responsible for coccygodynia and/or incomplete cauda equina syndrome. Their presence is suggested by the characteristics of the symptoms which are paroxysmal, exacerbated in standing position, relieved in dorsal position and revived by percussing the sacrum. Treatment is medical in most cases. The decision to operate depends on the persistence and intensity of pain and on whether signs of neurological defecit are present. PMID- 2096432 TI - [Genital sites of giant-cell arteritis]. AB - Temporal arteritis is one of the localisation of the giant cell arteritis. The involvement of the female genital tract had been rarely reported with only 16 cases in the literature. We report 3 cases revealed by a tumor of the genital tract. Histologic features are found in the vessels of ovaries, fallopian tubes and myometrium. Only one patient had symptoms suggestive of temporal arteritis. PMID- 2096433 TI - [Neutrophilic leukocytosis of systemic or bacterial origin: discriminative C reactive protein?]. AB - Neutrophilic leucocytosis is frequent in systemic diseases and often leads to confusion with infective diseases. A C-reactive protein (CRP) level of 100 mg/l or more has been claimed to indicate a bacterial infection in over 80% of the cases. The purpose of this study was to test the discriminative value of CRP in patients with neutrophilic leucocytosis of bacterial or systemic origin. Sixty patients presenting with an inflammatory syndrome with neutrophilia entered the study and were divided into 2 groups. Group I comprised 30 patients with Horton's disease (n = 9), systemic vasculitis (n = 6), deep cancer (n = 5), connective tissue disease (n = 4) or Still's disease (n = 4). Group II consisted on 30 patients with infective diseases: septicaemia (n = 13), bacterial pneumonia (n = 12), pyelonephritis (n = 4) or cholecystitis (n = 1). In both groups the number of neutrophils was higher than 12,000/cubic mm. Mean CRP values were lower in group I (75.3 +/- 70 mg/l) than in group II (153 +/- 61 mg/l) (P less than 0.01). With values above 100 mg/l the specificity and sensitivity of CRP for infection were 45% and 55% respectively; the positive predictive value of CRP was 66% and its negative predictive value 76%. Specificity rose to 65% with a CRP level higher than 150 mg/l, and 74% for a CRP level higher than 200 mg/l, but such values were also observed in 4 patients of group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096434 TI - [Arterial hypertension in patients with obesity. Role of hyperinsulinism and insulin resistance]. AB - The association between arterial hypertension and obesity has been known for many years and demonstrated by epidemiological studies. The physiopathological mechanisms involved consist of increased extracellular volumes, hyperactivity of the sympathetic nervous system and the renin-angiotensin-aldosterone system, and abnormal ion exchanges between extra- and intracellular compartments. Recent studies have demonstrated an association between arterial hypertension and insulin resistance. Insulin resistance may well be the most important aetiological factor in this type of arterial hypertension as it stimulates both renal sodium reabsorption and sympathetic nervous system activity and reduces vascular Na-K-ATPase activity. PMID- 2096435 TI - [Intolerance to carbohydrates: the seven questions]. AB - The borderline between diabetes and intolerance to carbohydrates has been drawn on the basis of prospective studies which determined a glycaemic threshold marking the risk for microangiopathy. On the other hand, the borderline between intolerance to carbohydrates and normal glucose tolerance remains arbitrary: 25% for subjects who are intolerant to carbohydrates return to normal glucose tolerance within 10 years. This is due to the fact that intolerance to carbohydrates is a heterogeneous entity which should be dismembered according to the severity of insulin deficiency and to the degree of insulin resistance. Alteration of insulin secretion is perhaps the most specific marker of susceptibility to non insulin dependent diabetes, but insulin resistance is certainly the principal factor exhausting insulin secretion and leading to non insulin dependent diabetes. Insulin resistance and the hyperinsulinism it creates seem to facilitate atherogenesis, even when glucose tolerance is still normal, so that the oral glucose tolerance test is not only poorly reproducible but loses a great deal of its value in the early detection of vascular risk. Measurements of fasting and post-prandial glucose levels and of A1C haemoglobin, cholesterol, triglyceride, and HDL cholesterol levels usually make it possible to classify subjects into one of the three following categories: (1) no risk of macro- or microangiopathy; (2) diabetes with a risk of macro- or microangiopathy; (3) intolerance to glucose with risk of atherogenesis but no risk of microangiopathy. The oral glucose tolerance test probably remains useful within a small set of values that are either very slightly above normal or dissociated. Measuring blood insulin levels might be a better way of assessing the risk of atherogenesis, but the clinical use of this test requires evaluation. PMID- 2096436 TI - [Chronic myeloid leukemia: from cytogenetics to molecular biology]. AB - Chronic myeloid leukaemia (CML) is an excellent model for the study of molecular rearrangements caused by a cytogenetic anomaly associated with a disease. The formation of a Philadelphia chromosome by translocation between chromosomes 9 and 22 provokes the breaking and migration of a cellular oncogen (ABL), located in the 9q34 region, towards chromosome 22 and the 22q11 region where the PHL gene is situated. This gene is broken in the bcr area the rearrangements of which are specific to CML. The ABL and PHL genes fragments fuse together, creating a new hybrid gene which is transcribed into an 8.5 kilobase messenger RNA specific to CML. This RNA is translated into a 210 kilodalton protein whose abnormally high tyrosine kinase activity seems to contribute to the development of the disease. Genetic engineering techniques improve our understanding of CML molecular mechanisms and can be very useful to clinicians as they permit the diagnosis of CML in some cases devoid of chromosomal markers, and the detection of a possible relapse in marrow-grafted patients with a much greater sensitivity (one in 100,000 cells) than that of cytogenetics. PMID- 2096437 TI - [Sneddon's syndrome: review of the literature apropos of a case]. AB - The authors report the case of a young woman with Sneddon's syndrome and expose literature review. This rare entity is characterized by idiopathic livedo reticularis, ischemic stroke, and occasionally, mild arterial hypertension. Skin biopsy shows endarteritis obliterans of deep dermal arteries. The pathogenesis of this disorder is still unknown and the treatment is not clearly established. PMID- 2096438 TI - [Cutaneous neuroendocrine carcinoma. Apropos of a case]. AB - Cutaneous neuroendocrine carcinoma (CNEC) is a rare tumour. We report the case of a 75-year old woman affected with a rapidly progressive CNEC of the right cheek which kept recurring despite surgical excision followed by radiotherapy. The clinical features of CNEC are not specific. The tumour is located in the dermis, and the tumoral cells (Merkel cells) have a monotonous appearance. Gould's classification of these carcinomas into three types has a prognostic value. Immunohistochemistry is a mandatory complement to light microscope examination. It is very difficult to distinguish between CNEC and metastasis from a visceral small cell carcinoma. Treatment consists of surgery combined with radiotherapy. Chemotherapy was very successful in our patient and should be considered in other cases. PMID- 2096439 TI - [Inappropriate antidiuretic hormone secretion by hematoma of the caudate nucleus]. AB - The authors report the favorable evolution of one case of inappropriate antidiuretic hormone secretion after a cerebral hemorrhage limited to the caudate nucleus. The limitation of the lesions explains the transient desinhibition of ADH producing centers. PMID- 2096440 TI - [Kaposi's sarcoma complicating long-term corticotherapy for severe asthma]. AB - Kaposi's sarcoma frequently develops in patients with immune deficiency which may be drug-induced (corticosteroids, immunodepressants). We report a case of Kaposi's sarcoma in a 75-year old man who had been taking oral prednisone continually for 7 years as treatment of severe asthma. Data from the literature clearly show that corticosteroid therapy may trigger the development of Kaposi's sarcoma in patients who usually possess several other pathogenetic factors of that disease, such as pre-existing immune deficiency, environmental (viruses) or genetic factors. In some cases, withdrawing corticosteroids may result in complete remission of the cutaneous lesions. PMID- 2096441 TI - [Agranulocytosis and connectivitis different from Felty's syndrome: 4 cases. Success of cyclosporin in a case]. AB - Four cases of chronic agranulocytosis in patients with systemic diseases different from Felty's syndrome are reported. Two patients had primary Sjogren's syndrome (confirmed in one, suspected in the other), one had systemic lupus erythematosus and the last patient had an unclassifiable connective tissue disease. Only one severe infection was recorded. The pathophysiological mechanisms involved are discussed. There is a strong suspicion that the cytopenia is of immune origin. Corticosteroid therapy was effective in all four patients. One patient who could not tolerate corticosteroids was successfully treated with cyclosporin A. PMID- 2096442 TI - [Value of biopsy of accessory salivary glands for the diagnosis of amyloidosis]. AB - There are few reports of amyloidosis diagnosed by deliberate biopsy of accessory salivary glands. Usually, a biopsy performed for dry mouth syndrome reveals an unsuspected amyloidosis. We report the case of 2 patients with lambda-type light chain monoclonal gammapathy complicated by generalized amyloidosis and in whom biopsy of the accessory salivary glands showed signs of amyloidosis. In the first patient accessory salivary gland biopsy was performed because these glands were enlarged, and the monoclonal dysglobulinaemia was subsequently diagnosed by serum immunoelectrophoresis. In the second patient with nephrotic syndrome, renal biopsy could not be carried out owing to the presence of a renal malformation; amyloidosis was confirmed by periumbilical fat aspiration, and a systematic biopsy of accessory salivary glands also showed evidence of amyloidosis. Biopsy of accessory salivary glands seems to be a particularly simple and safe method to detect generalized amyloidosis in patients with chronic inflammatory disease or monoclonal dysglobulinaemia. PMID- 2096443 TI - [Turner's syndrome and autoimmune dysthyroidism]. AB - The authors report a case of Turner's syndrome associated with Hashimoto's thyroiditis and present the various physiopathological hypotheses currently offered to explain the frequent association of an autoimmune pathology and a gonadal dysgenesis with an absence of X chromosome which is held responsible for autoimmunity. Is the chromosomal abnormality a factor predisposing to autoimmunity or does it result from a disturbance of the immune mechanism? Environmental factors, such as bacteria, viruses or some pollutants might be responsible for both the immune disorders and the chromosomal abnormality. The association of the two types of disease may also be accidental. In the present state of our knowledge, there is no answer to these questions. PMID- 2096444 TI - [Does hypothyroidism potentialize muscular toxicity of fibrates?]. PMID- 2096445 TI - [A comparative analysis of patients with coronary stenotic and ectatic lesions]. AB - A total number of 177 patients with coronary lesions were studied. Sixty nine of them presented either a combination of stenotic and ectatic lesions (n = 18) or isolated ectatic lesions (n = 51) and 108 presented only stenotic lesions. Analyzing several clinical and epidemiological parameters we observed a significant difference with respect to the higher prevalence of hypertension among the group affected by ectatic lesions. We verified as well a higher prevalence of myocardial infarction in the group of ectasia associated to the stenotic lesions. Finally, a higher global mortality was observed in the group of ectasia associated to stenotic lesions after medical or surgical treatment. PMID- 2096446 TI - Sindrome de Poland. Presentacion de un caso. [Poland's syndrome. A case report]. AB - A case of Poland's syndrome in a 19-year-old male is briefly described. This syndrome is characterized by congenital absence of the pectoralis major and minor muscles as well as homolateral brachysyndactyly. The etiology is unknown. Surgical repair is aimed at constructing a functional hand. Chest deformities usually does not require surgery except in cases of lung herniation or breast hypoplasia. PMID- 2096447 TI - [The psychopathological aspects related to breast cancer]. AB - During the last 30 years, many articles have been published in scientific journals dealing with psychological aspects of breast cancer and its treatment. This work, through a bibliographic revision, tries to come across the psychopathologic and psychosocial data concerning breast disease. It exposes its influence on body image, symptom appearance (essentially psychopathology, marital and social adjustment) and sets up some adjustment predictors that can improve support for breast cancer patients. PMID- 2096448 TI - [The risk and treatment of hyperlipoproteinemias]. AB - The role of lipid disorders in the pathogenesis of coronary heart disease is reviewed. It is also presented the pathophysiology of hyperlipidemias and its current therapeutic policies. PMID- 2096450 TI - [Purpose in biology]. PMID- 2096449 TI - [Infectious complications in the orthoptic liver transplant]. AB - Orthotopic liver transplantation is a therapeutic option for selected patients with end-stage liver disease. Among the complications of orthotopic liver transplantation infectious problems are a major cause of mortality. In this report the different types of infection following orthotopic liver transplantation are reviewed. In addition, currently available data regarding to transmission of infectious agents from organ donor to transplant recipient are reported. PMID- 2096451 TI - [Pulmonary and pleural localizations of Kaposi's sarcoma in AIDS]. AB - Intrathoracic Kaposi's sarcoma (KS) in AIDS is remarkable for its frequency and severity. It is responsible for 10% of "pneumonias" and almost 50% of pleurisies observed in these patients. The time elapsed between the discovery of the lesion and the patient's death does not exceed a few months on average. The initial manifestations of pulmonary KS are usually discreet and consist of cough and/or dyspnoea in patients with KS of the skin and mucosae. Fever is lacking or moderate. The most suggestive radiological findings are dense, nodular, tumour like opacities and bilateral linear and/or micronodular opacities around the bronchi and vessels. The diagnosis rests on bronchial fibroscopy which shows red, non friable lesions which, to a trained endoscopist, are very characteristic. When these lesions are absent, thoracotomy may be necessary for diagnostic purposes. Treatment essentially consists of chemotherapy; zidovudine therapy and prophylaxis of pneumocystosis are indicated if the circulating CD 4 cell count falls below 200/mm3. When its symptoms are predominant, pleural KS is typically progressive, with normal or slightly elevated temperature, associated parenchymal lesions that are clearly visible on CT scans and copious, bilateral, blood stained serous or chylous pleural fluid. When these signs are absent throacoscopy or thoracotomy may be necessary. Future advances in this field will be due not only to improvements in chemotherapy but also to a better understanding of the physiopathology of intrathoracic Kaposi's sarcoma. PMID- 2096452 TI - [Diagnostic pitfalls, artefacts and difficulties of thoracic radiography]. AB - The antero-posterior X-ray film of the chest is still a basic examination in everyday clinical practice. It supplies multiple data but reading of the image is difficult and requires much accuracy and method. In this review paper we examine all the artefacts, pitfalls and diagnostic problems we have encountered in many years of experience, irrespective of their cause (technical, iatrogenic) or origin (parietal, intrathoracic, pleural, vascular, gastrointestinal, mediastinal, pulmonary). We consider that all pneumologists should have in mind these problems when faced with doubtful or abnormal radiographs of the chest. PMID- 2096453 TI - [Abnormalities of respiratory function in civil defence firefighter-submarine divers. Respective role of diving and occupational exposure related to occupational firefighter's functions]. AB - Lung function was studied in 20 firemen-submarine divers (mean age 36 +/- 1.2 years) of the French civil defence undergoing the medical check-up compulsory for professional divers (lung function tests are not systematically performed in ordinary firemen). Compared with the CECA standards: (1) vital capacity (VC) was increased, residual volume (RV) was decreased and total lung capacity (TLC) was unchanged; (2) with the exception of peak respiratory flow, all expiratory flow values (FEV1, MEF50, MEF25) were decreased; (3) the permeability factor (KCO) was decreased. These functional abnormalities were moderately worse in subjects who smoked. Some abnormalities (increased VC, decreased RV) are typical of diving activities, but the deterioration of effort-dependent expiratory flow values and alveolar-capillary diffusion must be ascribed to specific nuisances (fumes, polluants, toxic substances) associated with fireman's activities. Monitoring lung function in all professional firemen therefore seems to be necessary, if not indispensable. PMID- 2096454 TI - [Radiological case: a peculiar ganglio-pulmonary involvement]. PMID- 2096455 TI - [Extralobar pulmonary sequestration. A diagnostic pitfall]. AB - The authors report a case of dual malformation: pulmonary (sequestration) and mediastinal (pericardial). This case is original in that clinically and at standard radiography sequestration was mistaken for hydatid cyst. The diagnosis was corrected after anatomico-pathologicale examination of the operative specimen. PMID- 2096457 TI - Anatomic basis of a dorso-commissural flap from the 2nd, 3rd and 4th intermetacarpal spaces. AB - This study relates to an island skin-flap constructed on the dorsal aspect of the hand, between the heads of the 2nd, 3rd, 4th and 5th metacarpals. The vascular pedicle consists of the subcutaneous fatty tissue of the dorsal aspect of the proximal phalanx. This fatty tissue is richly vascularized by the dorsal branches of the proper palmar digital artery and by the periarticular circle of the proximal interphalangeal joint. The point of rotation of the flap is situated at the level of the proximal interphalangeal joint. The length of the pedicle allows the skin flap to cover losses of substance of the dorsal aspect of the middle and distal phalanges. Its chief advantage is that it does not sacrifice the proper palmar digital artery. PMID- 2096456 TI - [Intestinal metastasis of pulmonary cancers. Apropos of 2 cases]. AB - We report 2 new cases of intestinal metastases from lung cancer. Such metastases are not exceptional, but their clinical manifestations are rare and their diagnosis during evaluation of lung cancer is difficult. This diagnosis could be suggested by the presence of iron deficiency anaemia or melena in a patient being investigated for lung cancer. Other metastases are often present, and the prognosis is fatal at short term. PMID- 2096458 TI - Basic vascular anatomy and the reimplantation of the amputated hand through the palm. AB - Thirty adult upper extremities were used to study the blood vessels of the hand by angiography, cross-sectional measurement and operative microscopic dissection. The arteries in the middle segment of the palm are arranged in three planes, while in the upper or lower segment there are two planes only. The division of the territories of the radial and ulnar arteries are not same in the three different layers. There are three main anastomotic pathways between the radial and ulnar arteries in the radial-ulnar direction, while in the palmar-dorsal direction there are three anastomotic zones between the palmar and dorsal planes. According to the rate of appearance, sources, cross-sectional area, irrigation territories and anastomoses of the arteries in the three segments, the clinical significance in the reimplantation of the amputated hand through the palm has been discussed. PMID- 2096459 TI - Arterial vascularization of the operated stomach: highly selective vagotomy, anterior lesser curve seromyotomy, esophageal replacement by transposed stomach after esophagectomy or circular pharyngolaryngectomy. AB - The rich vascularisation of the stomach is well known and the remarkable tolerance of the organ to vascular ligatures has been emphasised. However, some clinical observations as well as more and more detailed anatomical studies suggest some modification of this classical concept, especially when operating on the viscus. The aim of this work was to evaluate particularly the importance of parietal ischemia which follows hyperselective vagotomy and the more recent anterior seromyotomy, on the one hand, and the gastrolysis that precedes gastro esophagoplasty after esophagectomy or circular pharyngolaryngectomy on the other hand. The stomachs of 40 unembalmed adult cadavers were studied by angiography in various ways, according to the operation which was being considered. The findings indicated that hyperselective vagotomy caused an avascular band 2 cm wide along that part of the lesser curve affected by the surgical intervention, and that anterior seromyotomy (allowing for some technical artifacts) caused almost no parietal ischemia, and lastly, that the ischemia from gastro-esophagoplasty varied according to the technique used. Useful conclusions, supported by numerous illustrations, will allow the surgeon to define better the vascular requirements when choosing the procedure to be used, taking account of the clinical situation. PMID- 2096460 TI - Microsurgical anatomy of VII and VIII cranial nerves and related arteries in the cerebellopontine angle. AB - The relationships of VII and VIII cranial nerves and related arteries are reviewed in 26 preparations by microdissection techniques. These vessels may be grouped in large (AICA, PICA), medium (LA, SA, CSA, RPI) and small calibre (vasa nervorum, radicular and medullar branches). The importance of these structures in acoustic neuroma surgery, vestibular neurectomy and cross-compression syndromes is discussed. "Vascular loops" and "elongated arteries" are normal structures present at birth. PMID- 2096461 TI - Median nerve entrapment. Pronator teres syndrome. Surgical anatomy and correlation with symptom patterns. AB - The surgical anatomy of interest in the pronator teres syndrome was studied to shed light on the ramifying pattern of the median nerve, the number of its muscular branches and their branching levels and to pinpoint the location of the fibrous bands which may cause median nerve entrapment. The fibrous arch of the pronator teres muscle (pronator arch) was found to lie 3 cm to 7.5 cm below Hueter's line, that of the flexor digitorum superficialis muscle (superficialis arch), which is distal to the pronator arch, was found to lie 6.5 cm below Hueter's line in its most proximal position. Symptom patterns in terms of muscle weakness caused by median nerve entrapment at different levels were also evaluated. PMID- 2096462 TI - Holographic interferometry in the biomechanical study of femoral behavior, with and without prosthesis. AB - The authors studied the strains acting on a normal femur, and on the same femur fitted with an uncemented screwed prosthesis, by means of the method of holographic interferometry. This modern optical method has the advantage of not requiring any preparation of the surfaces or modification of the bone to be studied. It is non-destructive and can be repeated. This study required 40 interferograms for each case, using two or even three views. Comparison of the images obtained showed major modifications: disappearance of the physiologic flexion of the diaphysis, overload of the upper third, and zones of excess constraint. PMID- 2096463 TI - The papillary muscles of the left ventricle and the cardiac segments. AB - The relationship between the arterial anatomicosurgical segments and the papillary muscles of the left ventricle was investigated in 38 human hearts of adult individuals of both sexes. The specimens were studied after (a) vinyl acetate injection and corrosion (28 hearts) or (b) formaldehyde fixation (10 hearts). In 4 of the corrosion casts, the cardiac chambers were not filled with the plastic substance and, prior to corrosion, the position of the papillary muscles was marked with threads or pins. The anterior papillary muscle was related to the (a) anterior interventricular segment (I SV); (b) lateral (II SV); and (c) left marginal segment (III SV). The medical portion of the anterior papillary muscle is supplied by the artery of the I SV whereas the lateral portion is supplied by the artery of the II or III SV. The posterior papillary muscle was related to the (a) anterior interventricular segment (I SV); (b) left marginal (III SV); (c) posterior interventricular segment (III DV) and (d) posterior ventricular (IV SV). As a rule, the papillary muscles are supplied by more than one segmental artery, therefore, anatomical variations may play an important role in functional alterations produced by ischemic lesions of the myocardium. PMID- 2096464 TI - Evaluation of encephalic ventricular volume from the magnetic resonance imaging scans of thirty-eight human subjects. AB - Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for "normal" subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm3, while that for males was 16.3 cm3 and that for females was 18.0 cm3. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age. PMID- 2096465 TI - The fibrous frame of the supraspinatus muscle. Correlations between anatomy and MRI findings. AB - 30 MRI investigations of shoulders and 20 dissections of non embalmed cadaveric shoulders allowed us to demonstrate a particular organization of the supraspinatus muscle. In the anterior part of the muscle is an important fibrous frame with obliquely inserted muscle fibers. This organization suggests that this part of the supraspinatus muscle works as a "contractile tendon". PMID- 2096466 TI - Embolisation of the ophthalmic artery branches distal to its visual supply. AB - A study of the embryology and the anatomy of the ophthalmic artery shows that the branches to the important sensory structures arise proximal to the second intraorbital segment of the vessel. Damage to vision will be avoided if embolisation is restricted to vessels anterior to this "safety point", which is easily recognised on an angiogram. The ideal point of injection of emboli is even more distal and varies with the extent of the lesion and the material used. Three cases are described with vascular lesions supplied by the ophthalmic artery and embolised with Histoacryl. PMID- 2096467 TI - Intraparenchymal pulmonary lymph node: case report and literature review. AB - A case of a 44-year-old woman with a solitary pulmonary coin lesion is presented. Histologic study of this nodule revealed a normal intraparenchymal pulmonary lymph node. A review of the literature discusses the incidence and characteristics of this entity. PMID- 2096468 TI - Pseudocoarctation of the aorta associated with retro-aortic left brachiocephalic vein: a case report. AB - The authors report a case of pseudocoarctation of the aorta associated with a retro-aortic left brachiocephalic vein. This exceptional congenital malformation, never described before, was studied by aortography, computed tomography and magnetic resonance imaging. PMID- 2096469 TI - The role of interleukin-4 in IgE and IgG subclass formation. PMID- 2096473 TI - Urinary mercury clearance of dental personnel after a longterm intermission in occupational exposure. AB - The objective of this study was to get an estimate of the overall halftime for clearance of urinary mercury after cessation of a mercury vapor exposure. Ten dentists and dental nurses were selected and their urinary mercury excretion rates prior and after a summer vacation were measured. Estimates of their basic mercury excretions, originating from the environmental background and their own amalgam restorations, were individually subtracted to get the contributions deriving from occupational work. If assuming a first order of kinetics for the clearance of urinary mercury a median value of 41 days was achieved for the halftime searched, a value somewhat lower than those previously published. An explanation might be that the tailing effect of the decay curve here was eliminated by the taking of the background excretions into account. PMID- 2096472 TI - Malignant tumours in Swedish dental personnel: a comparative study with the total population as well as with some specific occupational groups. AB - By linking the records between the Swedish census of 1970 and the cancer register for the period 1971-1984 the question was investigated as to whether an increased risk of, in the first hand, tumours of the liver, the kidneys or the nervous system could be found among dental personnel, and if so, whether it could be correlated with age. No significant higher risk could be demonstrated for any of these sites of tumours, neither for dentists, nor for dental nurses, dental technicians, nor for dental personnel collectively in comparison to the risk in the general Swedish population. For dental personnel the SIR value for primary liver tumours was 1.3, 95% CI: 0.6-2.4, for tumours of the kidneys the SIR was 1.0, 95% CI: 0.6-1.5, and for tumours of the nervous system the SIR was 1.1, 95% CI: 0.8-1.6. When these groups of tumours were taken together, a significantly increased risk (p less than was found only for male dentists, where 33 cases were observed against 22 expected. This increased risk does not seem to have any counterpart in any other category of dental personnel, and therefore the significant figures may be interpreted as a chance result. The noticeably increased and decreased risk levels which were found in other sites of tumours for dentists could also be demonstrated in other groups with university education with one exception: haemo-lymphatic malignancies for which male dentists display a significantly lower risk. For all types of malignant tumours of dental personnel there was a nonsignificantly increased risk, the SIR = 1.07, 95% CI: 0.99-1.15.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096471 TI - Cytokine-induced human basophil/mast cell growth and differentiation in vitro. AB - The growth and differentiation in vitro of rodent mast cells, a process dependent upon interleukin (IL)-3, has already been well established. Only recently, however, have the mechanisms underlying the development in vitro of human metachromatic cells (basophils and mast cells) begun to be delineated. Precursors of human metachromatic cells are found in bone marrow, peripheral blood, cord blood, fetal liver and are represented by some leukemic cell lines. These are dependent upon the presence of several cytokines or accessory cells for their proper growth and differentiation. IL-3 as well as granulocyte-macrophage/colony stimulating factor (GM-CSF) appear to be the principal human metachromatic cell hemopoietic factors; contributory roles to metachromatic cell differentiation can also be shown for IL-5 and nerve growth factor. Stromal cell populations, including fibroblasts and epithelial cells, especially from allergic or inflamed tissue microenvironments, elaborate GM-CSF and possibly novel metachromatic cell differentiation factors. Questions remain regarding cell origins, specific hemopoietic factors and lineage inter-relationships for human mast cell subtypes and basophils. The intriguing possibility of mast cell-drived hemopoietic cytokines, which could perpetuate human allergic reactions, is currently under scrutiny. The relevance of existing data and future research in this area to diagnosis and therapy of a large group of human immune-inflammatory conditions is not to be underestimated. PMID- 2096470 TI - IgG subclass-restricted immune responses to allergens. AB - The IgG responses to a variety of allergens are predominated by IgG1 and IgG4 antibodies. With several allergens, the IgG1 response appears to precede the IgG4 response and this switch may be driven by repeated allergen exposure. It remains to be determined whether there is any causal relationship between subclass restriction and the regulation of specific IgE. The question of whether IgG4 antibodies are protective or pathological is still unresolved. Human models are needed to further analyze the interrelationships between T cells, cytokines and B cell isotype expression. The antibody response to allergens appears to be an ideal experimental system for studying antigen-specific isotype regulation in humans. The subclass patterns are remarkably reproducible between individuals, and allergic and normal human subjects, who have been immunized naturally or therapeutically, are readily available as a source of cells. Isolation of allergen-specific T cells that putatively regulate subclass expression would seem to be a worthwhile endeavor. Understanding the molecular and cellular events that initiate and control isotype expression will play an important role in the rational design of immunogens and therapeutics, aimed at optimizing protective immunity and diminishing the pathological effects of autoimmune and allergic responses. PMID- 2096474 TI - Dental caries in players belonging to a Swedish soccer team. AB - Since dental caries is associated with frequent use of sugar-containing products and since there is a potential risk for such a consumption among sportsmen, we conducted a clinical study of a group (n = 30) of 17-30-year old elite soccer players, including DFS and various caries-related factors, such as plaque index, numbers of cariogenic microorganisms in saliva and sugar intake frequency. Each player was asked to identify one friend of the same age, sex and social background but not active in any sport (n = 28). The mean values for DFS, plaque index, mutans streptococci and lactobacilli were less favourable for the players, but none of the differences were statistically significant, except for the dietary score (p less than 0.05). Thus, soccer players on an elite level seem to have a somewhat higher risk to develop dental caries than nonplayers. However, their regular use of fluoride-containing toothpaste probably to some part compensates for this increased risk. PMID- 2096476 TI - Tensile and shear strength of orthodontic bracket bonding with glass ionomer cement and acrylic resin. An in vitro comparison. AB - The tensile and shear strength for a polyalkeonate luting cement (AquaCEM) and a no-mix acrylic resin (Unite) in orthodontic bracket bonding were compared in an in vitro test. Brackets bonded/cemented to extracted premolar teeth were subjected to loads in a universal testing apparatus and the dislodging forces were recorded. The possible influences of setting time and of bracket base design were also studied. No significant differences between the cement and the resin were found after allowing 24 hours of setting time. This in contrast to the significantly stronger tensile strength but inferior shear strength for the polyalkeonate cement when stress was applied after 15 minutes. A significantly higher tensile strength value was recorded for a foil-meshed bracket base type compared to an integral base type with cut grooves after 15 minutes, but not after 24 hours. While the polyalkeonate cement adhesion mostly fractured within the cement layer, the acrylic bond more often failed in the enamel-adhesive interface. The results support the use of the fluoride-containing cement as an alternative to acrylic adhesives in orthodontic bracket bonding, especially in high-risk caries patients. PMID- 2096475 TI - Glass ionomer cements as a fluoride release system in vivo. AB - Fluoride release to saliva from three glass ionomer cements, Vitrabond, Ketac Fil, and ChemFil II, was followed for six weeks in vivo. Colony forming units (CFU) of S. mutans present in saliva before and after placement of glass ionomer restorations were analysed. Thirty-six children received 1-6 glass ionomer cement restorations of one of the three materials. Unstimulated saliva was collected and analysed before insertion of restorations (baseline measurement), immediately after treatment, after 3 weeks and after 6 weeks. The fluoride concentration was measured according to a method slightly modified from Ekstrand (1977) and Duckworth et al. (1987). Baseline concentration of fluoride was between 0.038 and 0.050 ppm. Immediately after placement of GIC restorations, fluoride concentrations increased to 0.8 for ChemFil II and 1.2 ppm for Ketac-Fil and Vitrabond. After 3 weeks, concentrations of released fluoride decreased about 35% for all three materials, and after 6 weeks, concentrations decreased another 30%. However, still after 6 weeks, the fluoride concentrations of unstimulated saliva was 10 times higher than the baseline values. The more restored teeth surfaces the higher was the saliva fluoride concentration found. The prevalence of S. mutants in saliva decreased after placement of the GIC restorations. PMID- 2096477 TI - Effects of the new undergraduate dental curriculum of 1979. AB - A new curriculum for dental education was introduced in Sweden in 1979. Among other things the basic training was cut down from 10 to 9 semesters and a preregistration year in the Public Dental service was added. In this study two cohorts of dentists, one having studied under the old and one under the new curriculum, having 1 to 3 years practical experience of the dental profession, were asked to evaluate their undergraduate education as seen from a practising dentist's point of view. The results showed that the dentists trained under the new curriculum regarded their theoretical knowledge, clinical skills, and the relevance of their training generally higher than those trained under the old curriculum. However, the correlations between the old and the new curriculum with respect to the rankings of the individual subjects were high, indicating that no radical changes had occurred in the preference orders of the subjects. The self estimated importance of different subjects for the dental profession may reflect the dentists' present working situation, e.g. the Public Dental Service or private practice. PMID- 2096478 TI - [Endocrinological diagnosis of normocyclic functional sterility]. AB - Normocyclic functional sterility can be regarded as a starting point to the common pathophysiology of different endocrinopathies. Those are finally leading to secondary amenorrhoea, as the most severe sign of ovarian insufficiency. The incidence of abnormal hormonal parameter increases parallel to the duration and the extent of the respective endocrinopathy. For a better causal classification of the endocrine disorder a complete hormonal assessment is mandatory, as characteristic historical data or significant clinical signs will often be missed in infertile patients. The completion of one single basic hormonal examination might lead to an exact differentiated diagnosis and then allows accordingly for the induction of a purposeful treatment. The pregnancy rates are considerably high proving the effectiveness of the thoughtful pretherapeutic diagnostic evaluation. The principle of cost-effectiveness is as well maintained by the follow-up of complete diagnosis and master-tailored therapy. PMID- 2096479 TI - [Steroid receptors in the gestagen treatment of endometriosis]. AB - In 35 patients with laparoscopically proved endometriosis we determined the cytosolic estrogen and progesterone receptor content in endometrial samples before and after a 3-month course of progestagen treatment (DCC method). Dienogest was given in 20 cases, norethisterone in an other group of 15 patients. Compared with a normal group the receptor content was clearly higher in endometriosis patients. It correlated closely to the histological findings dated according to Noyes. In more than 60% of the pretherapeutic cycles there were some signs of disturbed differentiation. After 3 month of therapy the binding capacity of steroid receptors significantly decreased, particularly in norethisterone patients. Both clinical results and receptor conditions correspond to previous investigations concerning the competition behaviour, having confirmed different binding affinity to the receptor for the two gestagens here tested. PMID- 2096480 TI - [Clinical experiences with femovan (Gynera)]. AB - The low dose oral contraceptive Femovan/Gynera which contains 0.03 mg Ethinylestradiol and 0.075 mg Gestoden was examined in several clinical trials. Those trials proved its contraceptive effectiveness, its controlling influence on the menstrual cycle and a low incidence of unwanted side-effects. The data reported are based on the experience of more than 100,000 women representing nearly 600,000 treatment cycles. The results of all the different investigations compiled here underline a high contraceptive effectiveness and excellent control of the cycle when using the respective preparation. The rate of unwanted side effects was low. PMID- 2096481 TI - [Hormone substitution in the female climacteric--goals, means, effects]. AB - Traditional beliefs about climacteric symptoms and widespread imaginations about unwanted effects of estrogens in the pill have long been interfering with the recommendation of an early onset of effective replacement therapy. The somatic symptoms of rush or genital atrophia have later on been classified as hard evidence to justify a therapy, much more than the predominant psychic signs occurring in the postmenopausal years as mental depressions, decrease or lacking of libido, nervousness, insomnia. Those signs were neglected as weaker indications responding even to a placebo treatment. The present knowledge understands somatic and psychosomatic signs as an entiety, both being accessible to hormonal replacement therapy. 85% of the postmenopausal signs can effectively be treated with hormones. What is now known about atherosclerosis, lipid metabolism and osteoporosis in ageing woman adds further justification to even the prophylactic use of estrogens. Natural estrogens administered orally, transdermally or parenterally are the means of choice. The dosage might be tailored on the relief of symptoms (and afterwards reduced to a mere maintaining dosage), or given in a fixed cyclic regimen. The treatment cycle will be three or four weeks, a progestogen should be added for the last 12-14 days. Only one estrogen-androgen combination has survived (Gynodian). The transdermal application (in three different concentrations) with administration twice a week is in progress. Indications and contraindications for transdermal estrogens are similar to estrogens administered orally. PMID- 2096482 TI - [Current approach in the diagnosis and therapy of alopecia in gynecology]. AB - With an increasing frequency patients complaining problems with their hair show up in gynecologic office practices. We observe cases with alopecia androgenetica; both alopecia climacterica and postpartualis, being subgroups of alopecia androgenetica. From symptomatic as well as from pathogenetic point of view two other forms can be subdivided, to be named alopecia diffusa and alopecia areata. At the Department of Obstetrics and Gynecology of the University of Heidelberg an outpatients consulting programme for women with androgenetic symptoms was established some years before. The diagnostic procedures for a possible classification of the alopecia was intensified. The search for underlying internal diseases and/or endocrinopathies will be the first step towards a pathogenetically correct diagnosis, and if there is no plausible explanation reached by that, the investigation will be extended for heavy metal tracing or for the detection of other ecological damaging influences. A local treatment with thymus gland preparations (Thymu-Skin) was examined by following the conditions of a protocol. After treatment with the preparation (Thymu-Skin) 73% of all cases show improvement of the alopecia. The formula seems to be an effective alternative to the hormonal therapy. It is easy to administer and has no side effects or contraindications. It proved also to be advisable for prophylactic use in combination with chemotherapy. PMID- 2096483 TI - [Sterility therapy of women in the course of time]. AB - In all eras and cultures infertility has been regarded as one of the worst female diseases. Consequently, infertility investigation has always been one of the central diagnostic and therapeutic problems in medicine. We have attempted a summary of the tremendous evolution of infertility investigation and therapy, culminating in the modern concept of investigation and therapy of the infertile couple as a unit. PMID- 2096484 TI - The anticoagulant and antithrombotic properties of hirudins. PMID- 2096485 TI - von Willebrand factor antigen is less sensitive than ristocetin cofactor for the diagnosis of type I von Willebrand disease--results based on an epidemiological investigation. AB - Recently, in an epidemiological investigation involving 1,218 children aged 11 14, we demonstrated that the prevalence of von Willebrand's disease, based on a low ristocetin cofactor activity (RiCof) in children with a personal and/or family history of hemorrhage, was at least 1% (Blood 1987; 69: 454). All the diagnosed cases had multimeric patterns typical of type I von Willebrand's disease (vWd). Since standardization of RiCof is difficult and the test is not easily performed in a clinical laboratory, we measured von Willebrand factor antigen (vWf:Ag) in all available unthawed plasma samples of previously investigated children by ELISA, to assess the relative sensitivity of this more simple test for diagnosing vWd. Separate normal ranges were calculated by non parametric methods for 0 and non-0 subjects, and for children and adults, since values were higher in non-0 subjects and in children. Taking into account the 90% confidence interval around the lower limit of the normal range, 7 (50%) of the 14 cases diagnosed by RiCof were detected by vWf:Ag. Furthermore, two new cases would have been diagnosed by vWf:Ag, leading to a relative Ag/RiCof global sensitivity of 64%. A similar figure was obtained when the two tests were compared in the group of relatives of the affected children. In conclusion, measurement of vWf:Ag seems to be definitely less sensitive than the RiCof assay for detecting patients with vWd, even in type I patients, and RiCof remains the test of choice for screening for vWd in hemorrhagic patients. PMID- 2096486 TI - Prediction of vitamin K response using the Echis time and Echis-prothrombin time ratio. AB - Echis carinatus venom contains proteases capable of activating both normal and descarboxy prothrombin. We showed this venom (Sigma) principally activates prothrombin with almost no factor X activation. Echis time in combination with prothrombin time can predict vitamin K responsiveness since the Echis time is usually normal in the presence of descarboxy prothrombin associated with vitamin K deficiency. 38 patients with abnormal routine prothrombin times (PT) had both coagulant and immunogenic factor II assays along with Echis times done before and after vitamin K. Of 22 patients responding to vitamin K, based on correction of PT, 21 had normal initial Echis times and of 16 not responding, 11 had abnormal Echis times, giving a sensitivity of 95.4% and specificity of 68.8% for vitamin K responsiveness. 90% of patients with a PT/Echis time ratio less than 1.3 and a prolonged Echis time did not correct their PTs with vitamin K therapy. The 5 non responders with normal Echis times all showed normal initial coagulant and antigenic prothrombin, but 3 had low F V and/or F VII. PMID- 2096487 TI - Subcutaneous desmopressin (DDAVP) shortens the prolonged bleeding time in patients with liver cirrhosis. AB - The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) shortens the prolonged bleeding time in patients with congenital or acquired bleeding disorders, including patients with uremia or liver cirrhosis. We carried out a double-blind, placebo-controlled crossover study in ten patients with liver cirrhosis to evaluate whether or not their prolonged bleeding times could be shortened by subcutaneous injections of DDAVP (0.3 microgram/kg), a more practical route of administration than intravenous infusions. One hour after DDAVP injection the bleeding time was significantly shortened (p less than 0.05). After 4 h, however, the bleeding time shortening was no longer statistically significant. There was no bleeding time change after placebo. Plasma levels of von Willebrand factor antigen (vWF:Ag) did not significantly increase after DDAVP or placebo. The study shows that subcutaneous DDAVP is an alternative method for short-term shortening of the bleeding time in liver cirrhosis. PMID- 2096488 TI - Increased heparin cofactor II levels in women taking oral contraceptives. AB - Heparin cofactor II (HCII) is a thrombin inhibitor present in human plasma whose activity is enhanced by heparin. HCII exhibits important homologies with antithrombin III, the main heparin-enhanced thrombin inhibitor. Cases of recurrent thromboembolism have been recently reported in patients with HCII deficiency. Since the use of oral contraceptives (OC) is associated with an increased risk of thrombosis, the study of the plasma levels of HCII was undertaken in women taking contraceptive pills. Plasma HCII levels were found significantly higher in 62 women taking low-estrogen content OC (1.20 +/- 0.28 U/ml) than in 62 age matched women not taking OC (0.94 +/- 0.16 U/ml) or in 62 men (0.96 +/- 0.19 U/ml). Significant correlations between HCII and fibrinogen levels were reported in the three groups. From the pooled data of the two control groups (men and women not taking OC), the normal range for plasma HCII levels was defined to be between 0.60 and 1.30 U/ml (mean +/- 2 SD). Two cases of low HCII levels (less than 0.60 U/ml) were found in the control groups, but none in the group of women taking OC. It is concluded that the use of oral contraceptives is associated with a rise in HCII levels and that the screening for HCII deficiency has to be performed at distance of any OC therapy. PMID- 2096489 TI - Two mutations of the factor IX gene including a donor splice consensus deletion and a point mutation in a Dutch patient with severe hemophilia B. AB - The abnormal factor IX gene of a patient with severe hemophilia B (hemophilia B Ursem) was selected for study. All of the coding and their flanking regions and parts of the 5'- and 3'-untranslated regions of the factor IX gene were amplified from the patient's genomic DNA by using the polymerase chain reaction (PCR). By analyzing the nucleotide sequence of the PCR products we have identified two mutations in the patient's factor IX gene, viz. a tetranucleotide deletion (GAGT, nt 6492 to 6495) or (TGAG, nt 6491 to 6494) in the 5'-donor splice site consensus at the exon 2-intron B boundary, and a point mutation at nucleotide 31103 in the catalytic domain (exon 8) of factor IXa, which changes the codon for valine 328 (GTT) to one for isoleucine (ATT). PCR-amplified exon 8 from 45 normal males and 55 normal females had the codon for valine-328. We propose that the deletion within the donor splice-site consensus is the cause of the disease in this individual, whereas the substitution of valine-328 by isoleucine may be a neutral variant which is, at least, very rare in the normal population. In a family study the DNA sequence of the patient's mother shows both the G to A transition in exon 8 and the 5'-donor splice consensus deletion in intron B in one allele. PMID- 2096490 TI - Formation and persistence of procoagulant and fibrinolytic activities in circulation after strenuous physical exercise. AB - Seven healthy male volunteers were subjected to exercise of short (STR; 1.7 km), middle (MTR; 4.8 km) and long (LTR; 10.5 km) term runs at a speed close to maximal capacity. Blood samples were drawn before, immediately after exercise and at intervals over the next 10 h. FVIIIR:Ag (von Willebrand factor) rose 2.2-3.2 fold and persisted at higher levels than baseline during the observation time. A spontaneous drop in FVII (p less than 0.03) was found immediately after STR (13.5 +/- 2.5%) and LTR (18.3 +/- 2.4%), whereas only a minor decrease (7.5 +/- 6.5%) occurred in MTR. The procoagulant activity of monocytes isolated from whole blood exposed to LPS showed a striking enhancement in STR and MTR. An immediate enhancement in fibrinolytic activity was found in all groups (p less than 0.03) assessed by increased plasma levels of t-PA and shortened whole blood clot lysis time (WBCLT). The transient shortening of WBCLT was succeeded by a tendency to prolongation of the lysis time. A 45-year old male differed markedly from the others by demonstrating an extreme and consistent prolongation of WBCLT. Thus, it has been speculated that strenuous exercise possibly makes a subject more susceptible to a thrombotic event. PMID- 2096491 TI - Correlation between progressive adsorption of plasminogen to blood clots and their sensitivity to lysis. AB - The binding of plasminogen to preformed human plasma clots immersed in citrated human plasma was measured and correlated with the sensitivity of these clots to lysis with recombinant tissue-type plasminogen activator (rt-PA), recombinant single-chain urokinase-type plasminogen activator (rscu-PA) or two chain urokinase-type plasminogen activator (tcu-PA, urokinase). When 0.15 ml plasma clots were compressed mechanically to about 1% of their original weight, and immersed in 0.15 ml plasma, 131I-labeled native plasminogen (Glu-plasminogen) adsorbed progressively from the plasma milieu onto the clot; binding was 3 +/- 1% (n = 10) after 1 h, 7 +/- 1% after 12 h and 12 +/- 1% after 48 h. This was associated with an increased sensitivity of the clot to lysis; 50% clot lysis in 4 h was obtained with 65 +/- 5 ng/ml (n = 3) rt-PA before and 30 +/- 5 ng/ml (n = 3) after 48 h preincubation in plasma (p less than 0.01), with corresponding values of 660 +/- 55 ng/ml (n = 3) and 280 +/- 25 ng/ml (n = 3) for rscu-PA, (p less than 0.01), and 800 +/- 85 ng/ml (n = 3) and 270 +/- 35 ng/ml (n = 3) for urokinase (p less than 0.01). Additional binding of plasminogen and increased sensitivity to lysis were reduced or abolished when the clot was preincubated in plasminogen-depleted or in t-PA-depleted plasma, or when 20 mM 6-aminohexanoic acid or 2,000 KIU/ml aprotinin were added.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096492 TI - The anticoagulant mechanism of action of recombinant hirudin (CGP 39393) in plasma. AB - We studied the inhibitory action of recombinant desulphatohirudin (CGP 39393) on thrombin generation in whole plasma. Human plasma was activated either with thromboplastin or factor IXa. Hirudin delayed thrombin generation, but it was unable to prevent the explosive appearance of thrombin. The dose-dependent prolongation of the lag phase of the intrinsic and extrinsic thrombin generation curve was not the result of titration of thrombin activity by hirudin but the result of a delayed formation of the prothrombin converting complex (prothrombinase). In case of extrinsic activation, hirudin did not affect factor Xa generation, but prolonged the lag phase of the factor Va generation curve, causing its appearance when factor Xa generation was already in the decay phase. Because of its inhibitory action on the thrombin-mediated activation of factor VIII, hirudin prolonged the lag phase of the factor X converting complex that consists of factor IXa and factor VIIIa. Our observations with hirudin are in keeping with the notion that inhibition of the thrombin-mediated amplification reactions in blood coagulation is a very efficient way to delay or inhibit completely thrombin generation. However, although hirudin neutralizes stoichiometric amounts of thrombin, the interaction between in situ generated thrombin and hirudin appears not to be fast enough to prevent trace amounts of thrombin to activate factors VIII and V. Consequently, an explosive thrombin generation is observed even when free hirudin is present. PMID- 2096493 TI - Chlorobutanol, a preservative of desmopressin, inhibits human platelet aggregation and release in vitro. AB - Therapeutic preparations of desmopressin for parenteral use contain the preservative chlorobutanol (5 mg/ml). We show here that chlorobutanol is a potent inhibitor of platelet aggregation and release. It exhibited a significant inhibitory activity toward several aggregation inducers in a concentration- and time-dependent manner. Thromboxane B2 formation, ATP release, and elevation of cytosolic free calcium caused by collagen, ADP, epinephrine, arachidonic acid and thrombin respectively were markedly inhibited by chlorobutanol. Chlorobutanol had no effect on elastase-treated platelets and its antiplatelet effect could be reversed. It is concluded that the antiplatelet effect of chlorobutanol is mainly due to its inhibition on the arachidonic acid pathway but it is unlikely to have a nonspecific toxic effect. This antiplatelet effect of chlorobutanol suggests that desmopressin, when administered for improving hemostasis, should not contain chlorobutanol as a preservative. PMID- 2096494 TI - How much aspirin? PMID- 2096495 TI - Investigation of platelet/leukocyte interaction by whole blood aggregometry. PMID- 2096496 TI - The polymerase chain reaction and infectious diseases: hopes and realities. PMID- 2096497 TI - Synergism between arteether and mefloquine or quinine in a multidrug-resistant strain of Plasmodium falciparum in vitro. PMID- 2096498 TI - Quinoline esters as potential antimalarial drugs: effect on relapses of Plasmodium cynomolgi infections in monkeys. AB - Two compounds of the quinoline ester series, WR 197236 (6-butyl-4-hydroxy-3 methoxycarbonyl-7-beta-phenoxyethoxyquinoline ) and WR 194905 (4-acetoxy-6 decyloxy-7-isopropoxy-3-methoxycarbonylquinoline++ +), exhibit anti-relapse activity against sporozoite-induced Plasmodium cynomolgi B infections in rhesus monkeys. Both the compounds have been found to be curative when given intramuscularly in 7 daily doses of 15 mg/kg, and no relapses were observed during the observation period of 120 d. PMID- 2096499 TI - Clinical efficacy of mefloquine in children suffering from chloroquine-resistant Plasmodium falciparum malaria in Nigeria. AB - One hundred and thirteen children with symptomatic uncomplicated falciparum malaria were treated with either chloroquine 25 mg/kg body weight over 3 d (51 subjects) or mefloquine 25 mg/kg body weight single dose (62 subjects). The cure rate in the chloroquine group was 65% and in the mefloquine group 100%. 14 patients with chloroquine-resistant falciparum malaria (7 RI, 6 RII and one RIII) were successfully treated with mefloquine. The clearance times of parasitaemia and fever were 60 +/- 21.5 h and 24.7 +/- 10.1 h respectively in the chloroquine sensitive group and 52.3 +/- 18.2 h and 24.5 +/- 23.7 h respectively in the mefloquine group. In the chloroquine-resistant group treated successfully with mefloquine, these clearance times were 44.0 +/- 8.9 and 24.0 h respectively. The only remarkable adverse reaction in the chloroquine group was pruritus which occurred in 7 subjects. Abdominal pain and diarrhoea (8 subjects) and dizziness (3 subjects) were the only important adverse reactions in the mefloquine group. It is concluded that, despite previous reports of primary reduced susceptibility to mefloquine in vitro of some West African isolates of Plasmodium falciparum, this drug may be useful in the treatment of both chloroquine-sensitive and chloroquine-resistant falciparum malaria in West Africa. PMID- 2096500 TI - Audiometry as a possible indicator of quinine plasma concentration during treatment of malaria. AB - The spread of chloroquine-resistant malaria has led to a resurgence of quinine in clinical use. One of the well-known side effects of quinine, reversible hearing loss, is closely related to the plasma concentration. We suggest that this hearing effect could be used as an aid in therapy control when quinine drug assay is not available. PMID- 2096501 TI - Sustained protection against mortality and morbidity from malaria in rural Gambian children by chemoprophylaxis given by village health workers. AB - Mortality and morbidity from malaria were measured in children for a one-year period in a rural area of The Gambia 3-4 years after the introduction of a primary health care programme into some villages in the study area. Among children resident in primary health care villages who received treatment for febrile illnesses from a village health worker resident in their village there was no reduction in overall mortality or in morbidity from malaria compared with levels found in villages without a primary health care worker. However, among children aged 3-59 months who received malaria chemoprophylaxis from a village health worker in addition to treatment there was a 49% reduction in mortality and a 73% reduction in attacks of clinical malaria. The level of protection against malaria achieved by chemoprophylaxis given by village health workers 3-4 years after the chemoprophylaxis programme was started was as high as that obtained shortly after the introduction of the primary health care programme. PMID- 2096502 TI - Effects of untreated bed nets on the transmission of Plasmodium falciparum, P. vivax and Wuchereria bancrofti in Papua New Guinea. AB - The impact of untreated bed nets on the transmission of human malaria and filariasis in a village in a hyperendemic area of Papua New Guinea was studied. In anopheline mosquitoes, the Plasmodium falciparum sporozoite antigen positivity rate, filarial infection rates and human blood indices dropped significantly after bed nets were introduced. This reduction in human-vector contact did not affect mosquito density as no significant difference in either landing rates or indoor resting catches was found. The number of bed nets in a house and ownership of dogs were factors significantly associated with a reduction in the number of indoor resting mosquitoes. However, the reduction in the P. falciparum sporozoite antigen rate in mosquitoes was not accompanied by a reduction in either malaria parasite or antibody prevalences or titres against the P. falciparum circumsporozoite protein. PMID- 2096503 TI - Malaria and mosquitoes: how often for how long? PMID- 2096504 TI - C-reactive protein and the liver stage of Plasmodium vivax and P. berghei. PMID- 2096505 TI - Experience with the Becton Dickinson QBC II centrifugal haematology analyser for haemoparasites. PMID- 2096506 TI - Leishmania (Viannia) braziliensis isolated from cutaneous and mucosal lesions of patients residing in Tres Bracos, Bahia, Brazil differ in virulence for the golden hamster. PMID- 2096507 TI - The characterization of Leishmania major from Phlebotomus papatasi (Scopoli) caught in northern Sinai, Egypt. PMID- 2096508 TI - The importance of rapid diagnosis of new cases of cutaneous leishmaniasis in pin pointing the sandfly vector. PMID- 2096509 TI - Serum lipid and lipoprotein abnormalities in human African trypanosomiasis. AB - We have studied the serum lipoprotein system in human African trypanosomiasis (Trypanosoma brucei gambiense infection). The study was carried out on 74 Congolense patients suffering from sleeping sickness and 34 Congolense control subjects living in the endemic region of Boko Songho. We have determined the serum concentrations of lipids (triglycerides, cholesterol, phospholipids) and apolipoproteins (apolipoprotein A-I and B), and the separation of serum lipoproteins by electrophoresis. For the patients infected with T. b. gambiense, in comparison with control subjects, the results have shown (i) a significant increase in triglyceride concentration and a decrease in cholesterol concentration; (ii) a significant rise in apolipoprotein B concentration and a significant reduction in apolipoprotein A-I concentration; and (iii) an increase in low density lipoproteins and a decrease in high density lipoproteins. We conclude, therefore, that human African trypanosomiasis is associated with marked alterations in the composition and levels of host lipoproteins. PMID- 2096510 TI - The somnogenic T lymphocyte suppressor prostaglandin D2 is selectively elevated in cerebrospinal fluid of advanced sleeping sickness patients. AB - To help to elucidate the changes induced by Trypanosoma brucei gambiense in the central nervous system (CNS) in advanced sleeping sickness patients, levels of interleukin-1 (IL-1) and prostaglandins D2 (PGD2) and E2 (PGE2) were measured by radioimmunoassay in the cerebrospinal fluid (CSF) from 24 patients diagnosed on the criteria of CSF protein, leucocyte count and parasite presence as having CNS (i.e. late stage) involvement, and from 12 patients without CNS involvement. PGD2 concentrations were selectively and markedly elevated in the late stage patients. The increased PGD2 may in part account for the increased somnolence and the immunosuppression within the CNS. Measurement of PGD2 levels in CSF may be a useful criterion for CNS involvement. PMID- 2096512 TI - Entamoeba histolytica infections in flight personnel of an international airline. AB - A cohort of 99 subjects, members of the flight staff of Lufthansa German airlines, all infected with Entamoeba histolytica, were followed over a period of 2.5 years to monitor their clinical and parasitological status. All but 4 of the subjects were infected with non-pathogenic zymodemes of E. histolytica and had negative amoebic serology, and most were clinically well. One male heterosexual carrying a pathogenic zymodeme was found, despite massive treatment regimes, to carry the infection persistently for 12 months. Most non-pathogenic infections were left untreated. PMID- 2096511 TI - Infection with Pneumocystis carinii is prevalent in healthy Gambian children. AB - Pneumocystis pneumonia is rarely identified in the many immunosuppressed individuals with acquired immune deficiency syndrome (AIDS) and malnutrition in Africa. To test whether infection with Pneumocystis carinii occurs in the continent we conducted a comparative serological study, measuring by enzyme linked immunosorbent assay antibodies to the parasite in 150 healthy young individuals from both Britain and the Gambian savanna. The prevalence of significant titres of antibody to P. carinii steadily increased with age and included more than 70% of both populations by 8 years of age. Infection with P. carinii is, therefore, common in the Gambia. Thus opportunistic pneumocystis pneumonia may be an important but largely unrecognized disease in the continent, though its impact is probably diminished by the prevalence of fatal tuberculous infection, particularly in the AIDS population. PMID- 2096513 TI - Prevalence of Giardia in dogs in Malaysia: survey of a residential housing estate. PMID- 2096514 TI - Pathogenic zymodemes of Entamoeba histolytica remain unchanged throughout their life-cycle. PMID- 2096515 TI - Diagnosis of Strongyloides and hookworm infections: comparison of faecal and duodenal fluid microscopy. AB - Faecal microscopical diagnosis of Strongyloides and hookworm infections is insensitive. We have therefore compared duodenal fluid and faecal microscopy for detection of these parasites in a group of 292 patients being investigated for gastrointestinal symptoms who were examined by both techniques. Thirty-three of these patients (8%) were infected with Strongyloides stercoralis and 88 (30%) had hookworm infections. Microscopical examination of up to 3 faecal specimens detected only 33% and 65% of patients with Strongyloides and hookworm infections, respectively. Microscopical examination of a single specimen of duodenal fluid was more sensitive for detection of strongyloidiasis, identifying 76% of patients; the parasite was found exclusively in duodenal fluid (and not in faeces) in 67% of patients. For hookworm, the diagnostic sensitivity was similar with both techniques but duodenal fluid microscopy detected some patients (35%) who had not been identified by faecal microscopy. This study confirms previous work indicating the insensitivity of faecal microscopy in these infections and emphasizes the need to consider routine examination of duodenal fluid to exclude chronic strongyloidiasis. This may have particular relevance for south-east Asian war veterans and immunocompromised patients. PMID- 2096516 TI - Albendazole in the therapy of cutaneous larva migrans. PMID- 2096517 TI - Reinfection of Somali children with Trichuris trichiura after chemotherapy: relevance of immunostimulation. AB - The intestinal helminth status of an age-stratified sample (6 to 20 years old) from a Somalian community has been assessed and the typical pattern of highly aggregated parasite distribution found. A reinfection study on a sample of 40 children (treated and untreated with a pentapeptide identical to the active site of the thymic hormone thymopoietin) seemed to indicate that immunological factors play a significant role in modulating the population dynamics of infection in endemic communities. PMID- 2096518 TI - Effect of two successive annual treatments with single doses of ivermectin on microfilaraemia due to Wuchereria bancrofti var. pacifica. AB - Between 1986 and 1988 a single-blind, dose-ranging study was carried out in French Polynesia to determine the efficacy and tolerability of single 50, 100, 150 and 200 micrograms/kg doses of ivermectin in Wuchereria bancrofti carriers. Forty male microfilariae (mf) carriers between 18 and 50 years of age, in whom mf density was greater than or equal to 20 mf/ml, were treated twice at a one-year interval. Twelve months after the second treatment, in carriers who were given a dose greater than or equal to 100 micrograms/kg, mean mf density was 4-7% of the initial pretreatment mf density. Therefore, several successive annual treatments with single doses greater than or equal to 100 micrograms/kg of ivermectin should result in reducing mf densities to a very low level. Nevertheless, at 9 months after the second treatment, residual parasitaemia ranged from 1 to 2182 mf/ml (median 85) in 30 patients. Finally, in patients with pretreatment mf counts less than or equal to 150 mf/ml, mean mf density was 2.8 and 8.9 mf/ml, respectively, during the 2 six-month periods following treatment, while in patients with pretreatment mf densities greater than 150 mf/ml (median 1500) it was 92.3 and 334.1 mf/ml during the same periods. These results suggest that, when implementing filariasis control programmes, the best strategy might be administration of several treatments with a single dose of ivermectin every 6 months to the entire population, at least in French Polynesia. Afterwards, when mf densities had been reduced to a relatively low level (100-150 mf/ml), annual treatments could be considered. PMID- 2096519 TI - Comparison of adult somatic and excretory-secretory antigens in enzyme-linked immunosorbent assay for serodiagnosis of human infection with Paragonimus heterotremus. AB - Adult somatic antigen extract of Paragonimus heterotremus was compared with excretory-secretory (ES) antigen in an enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of human paragonimiasis. The absorbence values in ELISA using the adult somatic antigen were not significantly different from the values obtained using ES antigens (P greater than 0.05). The sensitivity of the ELISA using either antigen was 100%, but the specificity was 96% with somatic and 98% with ES antigens due to a cross reaction with fascioliasis sera. It appears that both somatic and ES antigens are effective antigens for use in serodiagnosis of human paragonimiasis heterotremus. PMID- 2096520 TI - Serological evidence of infection of dogs and man in Nigeria by lyssaviruses (family Rhabdoviridae). AB - A survey was conducted for serum neutralizing antibodies against 3 members of the Lyssavirus group (rabies, Lagos bat and Mokola viruses) in Nigerian dogs and humans. Of 463 unvaccinated dogs sampled, 142 (30.7%) had antibodies against rabies; 39.2% of the stray dogs were positive. Of 241 dogs tested, 17.4% had antibodies against Mokola virus and 5.8% against Lagos bat virus. 28.6% of human samples tested had antibodies against rabies and, of 158 human samples tested, 12 (7.5%) had antibodies against Mokola virus and 4 (2.5%) had antibodies against Lagos bat virus. PMID- 2096521 TI - Non-viraemic transmission of Thogoto virus: vector efficiency of Rhipicephalus appendiculatus and Amblyomma variegatum. AB - Previous studies have demonstrated that Thogoto virus is transmitted from infected to uninfected ticks when co-feeding on uninfected guinea-pigs, even though the guinea-pigs do not develop a detectable viraemia. Furthermore, tick to tick transmission is potentiated by factors associated with the salivary glands of ticks (saliva activated transmission). The vector efficiency of 2 ixodid tick species, Rhipicephalus appendiculatus and Amblyomma variegatum, for Thogoto virus was assessed using this model. The number of uninfected recipient ticks that acquired Thogoto virus when co-feeding with virus-infected ticks (donors) on uninfected guinea-pigs was determined. When nymphs of either tick species were employed as donors, there was no significant difference in the number of infected recipient nymphs. In contrast, a significant difference in the vector efficiency of adults ticks was observed: 77.0% of recipient ticks which co-fed with R. appendiculatus donor adults acquired Thogoto virus compared to 44.7% of recipient ticks which co-fed with A. variegatum donors. No significant difference in susceptibility to Thogoto virus infection was observed between recipient ticks of the 2 species. Thus, adults of R. appendiculatus are more efficient than A. variegatum in mediating non-viraemic transmission. PMID- 2096522 TI - Hypoadrenalism in patients with pulmonary tuberculosis in Tanzania: an undiagnosed complication? AB - Addison's disease is rarely diagnosed in most African countries although tuberculosis, one of its major causes, is a widespread problem. In this study adrenal function was assessed using the Synacthen test in 50 patients with chronic pulmonary tuberculosis admitted to hospital in Dar es Salaam. Sixteen patients (32%) had an impaired response. Two had subnormal basal cortisol levels, one of whom had a normal response to Synacthen. There was no significant difference between the patients with an impaired cortisol response and those with a normal response with respect to frequency of non-specific symptoms, weight loss and body mass index. The mean supine and erect diastolic blood pressures were, however, significantly lower in those with an impaired cortisol response compared to the normal cortisol response group (64 mm Hg vs 74 mm Hg supine (P less than 0.01), and 62 mm Hg vs 73 mm Hg erect (P less than 0.005]. Basal and one-hour plasma cortisol levels correlated significantly with systolic and diastolic blood pressure, and correlated negatively with duration of tuberculosis and diastolic blood pressure. These findings are consistent with reported observations in Zulu patients with pulmonary tuberculosis, and suggest that impaired adrenal function may contribute to morbidity and even mortality among patients with tuberculosis in Africa. Adrenal hypofunction should be considered in any tuberculosis patient with hypotension and poor response to chemotherapy. PMID- 2096523 TI - Tick-borne relapsing fever in central Tanzania. AB - Between October 1985 and September 1986, 488 children aged less than 15 years, 45 pregnant women, 21 other women and 18 men with tick-borne relapsing fever (TBRF) were seen at Mvumi Hospital, Central Tanzania. 88% of the children were less than 5 years old and 36% were less than 1 year. Twelve children were less than 1 month old and some of the 10 infants diagnosed at between 4 and 12 days of age were cases of congenital infection. The clinical features of TBRF in the children and pregnant women were compared with 129 children with a similar age distribution and 52 pregnant women, respectively, who had blood smears positive for malaria but negative for spirochaetes. The common presenting features in children with TBRF were a high fever, splenomegaly, convulsions, and meningism. The difficulty of differentiation from malaria is described. Severe disease in both children and adults was associated with high density of spirochaetes in blood smears. Of the 45 infected pregnant women, 22 (49%) went into labour. One of the deliveries was an abortion and 10 were preterm infants, 4 of whom died. There were no maternal deaths. The estimated overall mortality for children was 1.6%, and 2.3% for those aged less than 1 years; for the 95 children admitted it was 8.4%. Penicillin was a satisfactory treatment for all ages, with a relapse rate of 4.7%. Recommendations for patient management are given. PMID- 2096524 TI - Transient risk factors for acute childhood diarrhoea in an urban community of Papua New Guinea. AB - Transient risk factors may play an important role in the aetiology of acute diarrhoea. These factors have not been well elucidated. To assess them, we monitored 479 children below the age of 5 years living in a well-defined urban community in Port Moresby, Papua New Guinea, for one year, using the nested case control method with density sampling. Comparing the odds ratios, we found that eating food that had been kept for more than 12 h, eating away from home, temporary absence of mother from home for more than one day, and the presence of respiratory infection in the child, were statistically associated with an increased risk of diarrhoea. We conclude that these transient factors must be addressed if effective control of diarrhoea is to be achieved. We believe that further studies will identify the factors more precisely and provide a better understanding of the method we have employed. PMID- 2096525 TI - Preliminary investigation of diarrhoeal diseases among children in Sanaa, Yemen Arab Republic. PMID- 2096526 TI - Chlamydial genital infection in Algiers: a sero-epidemiological survey. AB - Using a microimmunofluorescence test, the prevalence of antichlamydial immunoglobulin (Ig) G in 720 people in Algiers was studied. 34 (36%) of women with low genital infection, 28 (30%) of 91 patients attending a cancer screening clinic, and 44 (100%) of prostitutes had antichlamydial IgG at a titre greater than or equal to 1:16. Among 180 women seeking a rubeola test, 48 (26.6%) had IgG titres greater than or equal to 1:16. 144 infants less than 3 months old were also tested and 16.6% of them had IgG titres greater than or equal to 1:160; 20 (20.7%) of 97 men with chronic urethritis had IgG titres greater than or equal to 1:16. Antibody titres suggesting active disease in prostitutes, patients attending the cancer screening clinic and women with low genital infection were found in 95%, 11% and 17% respectively. PMID- 2096528 TI - Synergy of antithrombin III concentrate and antivenom in preventing coagulopathy in a rat model of Malayan pit viper envenoming. AB - The effects of unrefined equine antivenom and antithrombin III (AT-III) concentrate on the coagulopathy induced by systemic envenomation by Malayan pit viper (Calloselasma rhodostoma; MPV) venom were investigated in a rat model. 37 rats received an intramuscular injection of MPV venom and serial blood samples were taken from the femoral vein for simple whole blood clotting tests and measurement of AT-III activity. 30 min after venom injection, treatment (antivenom, AT-III or both) was given intravenously. 6 rats were untreated and all developed uncoagulable blood and AT-III depletion 90-210 (median 180) min after venom injection. A combination of high dose AT-III concentrate (0.5 units/g) and antivenom (20 micrograms/g) prevented abnormal clotting (P less than 0.001), whereas AT-III alone, antivenom alone, or a combination of low dose AT III (0.25 units/g) and antivenom did not (P less than 0.05). These results suggest that the coagulation abnormality in MPV envenomation is secondary to activation of the coagulation cascade at several levels, and that treatment with antivenom alone may not be sufficient to reverse or prevent this phenomenon. PMID- 2096527 TI - Arboreal green pit vipers (genus Trimeresurus) of South-East Asia: bites by T. albolabris and T. macrops in Thailand and a review of the literature. AB - In Thailand 29 patients were proved to have been bitten by arboreal green pit vipers: 24 by Trimeresurus albolabris and 5 by T. macrops. They were studied in order to define the clinical effects of envenoming, to characterize the haemostatic abnormalities and assess the efficacy of Thai Red Cross antivenom. T. macrops caused only local painful swelling, neutrophil leucocytosis and thrombocytopenia. T. albolabris caused more severe envenoming with local blistering and necrosis, shock, spontaneous systemic bleeding, defibrination, thrombocytopenia and leucocytosis. There was no evidence of disseminated intravascular coagulation, but fibrinolytic activity was increased. Platelet function was normal. The product of admission venom antigen concentration and the delay between bite and admission was significantly higher in defibrinated patients than in those without severe coagulopathy. Antivenom (5 ampoules intravenously) restored blood coagulability, but there was persistent venom antigenaemia, associated in some cases with recurrent coagulopathy. The literature on bites by south Asian green pit vipers of the genus Trimeresurus is reviewed; these bites are common medical problems and causes of morbidity. The identification of individual species is difficult, but may be important if antivenom is to be improved and used appropriately. PMID- 2096529 TI - The significance of particle size of soils as a risk factor in the etiology of podoconiosis. PMID- 2096530 TI - Intestinal helminths in northern Namibia. PMID- 2096531 TI - Congenital malaria in Papua New Guinea. PMID- 2096532 TI - Leishmania infantum as a cause of cutaneous leishmaniasis. PMID- 2096533 TI - [The cytomorphology of goblet cells of the fetal intestine. Studies of the large intestine of cattle (Bos primigenius taurus)]. AB - In the region of the base of the intestinal crypts undifferentiated goblet cells display a configuration and constellation of organelles and membrane structures that are indicative of their importance for function. These images at this stage of development deliver a scenario of the mechanism of secretory granule production: aggregates of protein vesicles from the "transitional elements" (PALADE) of the granular endoplasmic reticulum are, so to speak, rolled up on the trans side of the Golgi apparatus by inversion of peripheral membrane segments of the innermost Golgi lamellae, thereby forming corpuscles. The origin of the capsulated vacuoles, which contain vesicles as single elements or as conglomerates, is well established. Their capsule consists of a trilaminar external and external and internal membrane; between them lies condensed material of the Golgi apparatus. In the opinion of the present author, the development of the ensheathed vacuoles represents a basic, more general mechanism. In contrast, the further steps of synthesis, for the formation of secretory granules, are more heterogeneous. Condensation of the vesicles and the inner capsular membrane results in the formation of a prosecretory granule, which in the basic element in the process of secretory granule production. The prosecretory granules develop singly or by fusion with other granules to give primary secretory granules. The complexity of this mechanism of secretory granule formation, however, becomes evident when considering the apposition of capsulated vacuoles and prosecretory- primary--secondary secretory granules, of prosecretory and primary secretory granules as well as prosecretory granules and secondary secretory granules. Generally, primary granules show a tendency to become secondary secretory granules or to fuse with them. During maturation of the goblet cells the secretory granules fuse to form larger mucous bodies in the theca by fusion of the laminae of the membranes; a final product, there is a homogeneous mucous mass devoid of membranes. PMID- 2096534 TI - Morphometric analysis of the development of the cortical layers and extension of the forceps major of the corpus callosum in the mouse. AB - The reduction of the forceps major of the corpus callosum was estimated quantitatively in relation to the lesions to the neocortex in animals to which methylazoxymethanol-acetate (MAM) had been administered on the 13 th, 15 th or 17 th day of embryonic development. The specimens which received a prenatal injection of MAM the 13 th or 15 the day of gestation show noticeable reductions in both the extension of the occipital neocortex and the forceps major of the corpus callosum. Parallelly in MAM 13 there is a significant reduction in cell density both in the deeper layers and the more superficial ones, whereas in MAM 15 only the supragranular layers seem to be altered. Such a quantitative analysis shows a close correlation among the decreases in the area of the forceps major of the corpus callosum, in the area of the occipital neocortex and in cell density of the infragranular and supragranular layers. PMID- 2096535 TI - [The human peritoneum and human peritonitis in ultrastructural and immunohistochemical studies]. AB - This paper describes observations of the normal and irritatingly changed morphology of the human peritoneum and about alterations in human peritonitis. The results were obtained by transmission- and scanning electron microscopy, immunohistochemical reactions, and other supplementary light microscopic investigations on surgically collected tissue material. Special attention was given to the superficial structure and the openings of the peritoneum. The superficial liquid film and the microvilli of the mesothelium are influenced by irritative conditions. In the human peritoneum, there are separated areas of small high and of large flat mesothelial cells. The small-cell areas of the peritoneum are connected with openings, special mesothelial cell glades, and cell migrations from deeper parts. There are signs of mesothelial secretion into the peritoneal cavity from mesothelial cells and intercellular spaces of the mesothelium too. The stomata--openings of the peritoneum--are of conditioned character. These depends upon the state of the superficial mesothelium and upon topical loci between the mesothelial cells. Special attention requires the so called Dreierpunkt. In peritonitis, there are also openings in the fibrin layer. On this condition, the superficial layer of mesothelium mostly becomes destroyed. The keratin reaction is the most essential among the immunohistochemical investigations. It allows to demonstrate preserved mesothelial cells in the deepness of inflammatory tissue in peritonitis. PMID- 2096536 TI - Ultrastructural study of small granule containing (SGC) cells in the lower mesenteric ganglion in drug treated guinea-pigs. AB - Small granule containing cells (SGC or SIF cells) in the lower mesenteric ganglion of the guinea-pig were studied in control and experimental animals. After reserpine administration a decrease of dense population of granular vesicles was found. After injection of nialamide and dopamine to the animals in SGC cells significantly increased the number and density of granular vesicles. No real efferent synapses were found on SGC cell processes, although sites with accumulated synaptic-like vesicles, mostly with a dense core, were often observed. PMID- 2096537 TI - Ultrastructural alterations in mouse spermatogenic cells after treatment with anticancer drug biocarbazine. AB - Single doses of anticancer drug biocarbazine (BC)--DTIC synonym--were injected intraperitoneally at 50 and 200 mg/kg body weight to sexually mature BALB/c mice. Among other features previously reported (Martinova et al. 1989) BC causes ultrastructural alterations in spermatogonia and spermatocytes significantly expressed after administration of higher dose. In addition BC induces some defects in acrosome formation of early spermatids in Golgi and cap phase, while spermatids in later stages of maturation showed marked resistance to BC treatment. PMID- 2096538 TI - The occurrence of the Golgi apparatus in mouse oocytes. Demonstration of thiamine pyrophosphatase activity. AB - Location of thiamine pyrophosphatase activity as a marker of the Golgi apparatus was studied ultracytochemically in mouse oocytes with germinal vesicle (OGV), oocytes at metaphase I (OMI) and oocytes at metaphase II (OMII), and further in cells of the respective cumulus oophorus serving as comparative objects. TPPase activity in cumulus oophorus cells and in OGV was found exclusively in the Golgi apparatus. In OMI the reaction product of TPPase activity was observed in isolated smooth vesicles, and in only one case in structures identifiable as the Golgi apparatus. In OMII the occurrence of TPPase activity was also recorded in isolated smooth vesicles in cortical cytoplasm and further, exceptionally, in smooth concentrically arranged vesicles or tubules. The TPPase activity was not present in vesicular complexes. The results have shown that after the resumption of meiosis the occurrence of the reaction product of TPPase activity drops abruptly due to the reduction of the Golgi apparatus. Changes affecting the Golgi apparatus after the resumption of meiosis are related to the loss of the nucleus after the germinal vesicle breakdown. PMID- 2096539 TI - Ultrastructural characteristics of the cranial dura mater-arachnoid interface layer. AB - The ultrastructural features of the encephalic dura mater-arachnoid borderline (interface) layer (zone) of rats, rabbits, cats and humans were studied. The rat's interface zone included the electron-lucent epithelium-like arranged fibroblasts of the inner dural layer, the rich in filaments cells of the dural neurothelium, a 20 nm wide intercellular cleft filled with electron-dense material and the dark mitochondria-rich cells of the outer arachnoidal layer; in rabbits and cats, this laminar distinction was less prominent, while in man, it was almost absent. PMID- 2096540 TI - [A room in County Council's nest. Virpi gets a contract for her apartment. Interview by Carina Roxstrom]. PMID- 2096541 TI - [A room in County Council's nest. Charlotta must leave job behind in order to have an apartment. Interview by Carina Roxstrom]. PMID- 2096542 TI - [Monica gives hospice care--we offer our services and shelter, a last stopover before dying. Interview by Maria Ejd]. PMID- 2096543 TI - [New times in Czechoslovakia. Party-top's aerie is the people's hospital]. PMID- 2096544 TI - [Working with refugees gives new insight in health care. Interview by Jonny Saganger]. PMID- 2096545 TI - [Focus on work environment. The soul fares ill when the work environment is poor]. PMID- 2096546 TI - [Focus on work environment. We depend on the Working Living Foundation for help to improve the environment]. PMID- 2096547 TI - [Focus on work environment. Lack of influence makes the biggest problems. Interview by Maria Ejd]. PMID- 2096549 TI - ["Stripping of politics" (m)-medicine for health care]. PMID- 2096548 TI - [Summer holiday]. PMID- 2096550 TI - [Norwegians decreed higher salaries for women in laboratories]. PMID- 2096551 TI - [Pia has lifted Kisamor from dark obscurity. Interview by Elisabet Forslind]. PMID- 2096552 TI - [SHSTF's wage policy discussed at every working place. Interview by Jan Thomasson]. PMID- 2096553 TI - [7 years of wandering within the justice machinery]. PMID- 2096554 TI - [Do nurses go to the European court?]. PMID- 2096555 TI - [Inger Ohlsson on the 'no' of the Higher Court. Nurses have been sacrificed]. PMID- 2096556 TI - [Trouble over health center in Gavle--medical society says no to nurse as administrator]. PMID- 2096557 TI - [Solidarity strives for power, but not for many]. PMID- 2096558 TI - [We negotiate the same wages for everyone]. PMID- 2096559 TI - [Establish a committee of inquiry]. PMID- 2096560 TI - [Women and AIDS in the international AIDS meeting]. PMID- 2096561 TI - [One can learn not to put up with so much. Interview by Carina Roxstrom]. PMID- 2096562 TI - [They study health care economics in order to be better administrators]. PMID- 2096563 TI - [They must be allowed to show feelings. Interview by Carina Roxstrom]. PMID- 2096564 TI - [Intrigue bungles reforms in health care and nursing of the aged. Interview by Kaj Nyman]. PMID- 2096565 TI - [Social democrats and people's party agree on reforms in care for the aged]. PMID- 2096566 TI - [Quality circles stimulate]. PMID- 2096567 TI - [Students meet reality of nursing care. An operation is something to pin your hopes on. Interview by Carina Roxstrom]. PMID- 2096568 TI - [Students meet reality of nursing care. The school gives an ideal picture. Interview by Carina Roxstrom]. PMID- 2096569 TI - [Perspectives of child and adolescent psychiatric care]. PMID- 2096570 TI - [Stability, reliability and factor structure of a German version of the Children's Depression Inventory (Kovacs 1983)]. AB - A German version of the Children's Depression Inventory (Kovacs, 1983) was used three times in a study with 84 elementary school pupils (4th grade) aged between 9 and 12. The scale was sounded out on its psychometric properties. Results obtained offered a satisfactory reliability (Cronbachs's alpha between .81 and 87, Retest-reliability = .80 for an four weeks interval) and stability (r = .75 and r = .72 for intervals of 5 and 6 months). The factor analyses indicate that the German version of the CDI is an unidimensional scale. The results are compared with those of the American original and to other German CDI-Versions. PMID- 2096571 TI - [The problem of divorce in adolescence]. AB - In the available literature concerning divorce the situation of affected adolescents rarely is considered. In contrast to younger siblings who exhibit their distress in numerous ways, adolescents seem to be affected to a much lesser extent. Reexaminations over longer periods of time by Wallerstein and Kelly (1980) show however, that adolescents do have medium or long term impairments in their development: school and career problems, lack of emotional attachment and interpersonal relations are well above average. Own results are reported from the work with adolescents who experienced the separation and divorce of their parents, and compared with ideas of adolescents about partnership and marriage who are rather idealized and show a high level of morality. Experiences with a group of adolescents (thematic work) are outlined and compared with experiences from the literature. PMID- 2096572 TI - [Changes in the incidence of restrictive and confining measures in inpatient psychiatric treatment of children and adolescents with residential care experience before and after abolition of closed residential centers in Hamburg]. AB - Results from the investigation of 542 medical records of children and adolescents being admitted to the department of psychiatry of the university of Hamburg are presented and discussed. Analysis of medical records concerned the frequency of admissions in general, the diagnosis conduct disorder, the frequency of closed ward admissions and the item residential care. Data from a time period before (1976-1978) and after (1985-1987) abolition of closed ward admissions to the department of psychiatry among children and adolescents with a history of residential care. Due to the lack of research accompanying the administrative measure of abandoning closed residential care and the thereof resulting methodological problems, the obtained result can not be looked at as a substantial proof but indicates a correlation between the abolition of closed residential care and the increase in closes ward admissions to psychiatric departments. PMID- 2096573 TI - [Differential results of treatment in pedagogic-therapeutic long-term intervention in residential treatment centers for children]. AB - In a longitudinal evaluation study the developmental progress of 223 children, who have been treated between 1968 and 1987 in a residential facility for psychiatric care, was explored from referral until time of discharge. Initial state and state at discharge were defined multidimensionally according to MAS. Comparisons between children with different initial clinical diagnosis met expectations, that introversive disturbances recover more frequently than autistic as well as conduct disorders or hyperactivity. Associations between recovery and initial cognitive-intellectual state did not reach statistical significance, when type of disorder was controlled for. But rate of recovery appeared to be throughout higher for children with learning disabilities than for children without such deficits. Age at onset and age at referral were apparently rather irrelevant for the state at discharge. But rate of recovery was in general clearly reduced, when length of time between onset and referral had been above average. The relation between duration of treatment and state at discharge depended on the type of disorder. For children with conduct or autistic disorders the rate of recovery increased with longer duration of treatment, whereas for children with introversive disturbances the contrast was true. This could suggest confounding effects of severity of disorder. When the treatment in the facility had been precociously terminated, rate of recovery in general was remarkably lower than in case of a planned termination. Analysis on effects of alternative methods of treatment was only with restrictions possible and did not suggest a general or differential superiority of a special type of treatment. PMID- 2096574 TI - [The significance of genetic factors in the etiology of early infantile autism]. PMID- 2096575 TI - [The problem of communication in children with hearing disorders in relation to general aspects of the development of communicative behavior. A review]. PMID- 2096576 TI - [Comment on the report of the 21st scientific meetings of the German Society of Child and Adolescent Psychiatry by Prof. Remschmidt]. PMID- 2096577 TI - [Diagnosis and therapy in child and adolescent psychiatry]. PMID- 2096579 TI - [Aspects of impartial choice of filling materials]. PMID- 2096578 TI - [Development of child guidance centers in West Germany and West Berlin]. PMID- 2096580 TI - [Practice shock in dentists?]. PMID- 2096581 TI - [Paraplegic patients: use of teeth to handle environment]. PMID- 2096582 TI - Cisapride, a drug for long-term treatment? PMID- 2096583 TI - Long-term use of cisapride (Prepulsid) in premature neonates. AB - In order to study the effect of cisapride on gastric stasis and to evaluate the possible risk of cholestasis, 20 premature neonates born in the hospital during one year were orally treated with cisapride 0.15 mg/kg q.i.d., over a mean period of 38 days. The gestational age ranged from 26 to 34 weeks and the mean age at the start of the cisapride treatment was 18 days. All patients were ventilated, 13 had a respiratory distress syndrome (hyaline membrane disease), and 9 had gastro-oesophageal reflux (GOR). All patients were given a semielementary formula by means of a continuous nasogastric infusion. The gastric residue was studied during three days: 24 hour baseline and 48 hours under cisapride treatment. The mean residue decreased (p less than 0.0001) from 50.6% during the last 6 baseline hours to 12.1% during the last 6-hours of the cisapride period. The mean feeding volume increased from 24.2 ml to 34.2 ml (p less than 0.001). A group of four patients had reversible cholestasis against the background of an outbreak of Candida, three before and one during cisapride treatment. Therefore, it could not be demonstrated that cisapride plays a role in the development of cholestasis. Because of the risks of GOR and the drawbacks of delayed enteral feeding, it is concluded that the use of cisapride is justified in premature neonates with gastric stasis. PMID- 2096584 TI - [Vascularization of the pharyngo-esophageal transition zone]. AB - The arterial blood supply and the venous drainage of the area around the pharyngo oesophageal sphincter are still virtually unknown. We performed vascular injections with a gelatin-india ink solution on autopsy specimens. After fixation the specimens were dissected under a stereomicroscope. From our anatomic studies we conclude that the inferior thyroid artery gives rise to a special branch, the "laryngopharyngeal artery", that supplies the pharyngo-oesophageal sphincter through numerous transversal branches. This density can be explained by the oxidative metabolism of the cricopharyngeal muscle. This structural adaptation is necessary for the maintainance of a continuous tone within the pharyngo oesophageal sphincter. The pharyngo-oesophageal venous plexus in the laryngopharynx and cervical oesophagus provides rigidity to the surrounding corium and so ensures the integrity of the corium during sphincter relaxation. PMID- 2096585 TI - [Leiomyosarcoma of the small intestine in the young adult: unusual diagnostic approach]. AB - The authors report the case of a 40-year-old woman with fever and diarrhoea in whom a tumour of the small intestine was discovered by computerized tomography (CT), the barium meal being not contributory. Transcutaneous fine needle aspiration biopsies under CT guiding revealed a grade II leiomyosarcoma. Twenty months after radical resection, the patient is alive and asymptomatic. The authors review the literature about the histological grading and the immunocytochemical characteristics of leiomyosarcoma, its treatment and prognosis. PMID- 2096586 TI - [Primary ulcer of the small intestine. The value of peroperative endoscopy]. AB - A case of primary non-specific small bowel ulceration in a 39-year-old man is reported. Because of massive bleeding, an exploratory laparotomy was performed and the jejunal ulcer was discovered by fiberoptic endoscopy through a small jejunal enterotomy. The authors review the literature about the incidence, the diagnostic approach, the pathology, the aetiopathogenesis and treatment of this rare disease. PMID- 2096587 TI - A practical endoscopic procedure for jejunal intubation in presence of gastroparesia or (pseudo)-obstruction. AB - Patients with gastroparesia or intestinal pseudo-obstruction frequently have a motility disorder of the antro-pyloric region that makes the passage of tubes through the pylorus impossible or a very long procedure. We describe a rapid endoscopic method, inspired by the one used for nasobiliary drainage, that simplifies this procedure. In our manometric studies, we observed that spontaneous positioning needed a mean of 57 min (SD 34) in nondyspeptic subjects and a mean of 147 min (SD 68) in non-organic highly dyspeptic patients. Our method allowed us to shorten to a mean of 22 min (SD 5) the time needed to position the manometric tube and to start the recording of gastro-intestinal contractions in highly dyspeptic patients. PMID- 2096588 TI - The rationale for using ursodeoxycholic acid in chronic liver disease. AB - The authors make a review of the literature and of their personal experience about the possible mechanisms of action and the beneficial therapeutic effects of ursodeoxycholic acid in primary biliary cirrhosis. They postulate that owing to its hydrophilic properties, ursodeoxycholic acid is more efficiently absorbed by the ileum than the other bile acids, so replacing the other bile acids in the bile acid pool, and that ursodeoxycholic acid is less toxic for hepatocytes than the other bile acids accumulating in the plasma and is also a choleretic. PMID- 2096589 TI - [A historical case of laryngeal cancer (the death of Frederick III of Prussia)]. AB - The clinical evolution of the disease which lead to the death of Frederick III of Prussia on the 15th of June, 1888 is reconstructed through testimony of the times. The diagnosis of laryngeal cancer was made only after it was too late for surgery to have any effect and this delay was due to the differences in opinion between the attending laryngologists; particularly between that of the English physician Morell Mackenzie and the Germans Gehrardt and Bergmann. PMID- 2096590 TI - Pathology of soft tissue sarcomas. Selected current issues. AB - Soft tissue sarcomas are a heterogeneous group of malignant tumors with a wide range of clinical presentation, morphologic features and biologic behavior. During the past two decades, many acceptable new entities have been proposed, and the diagnosis and classification of these tumors have been modified. This paper reviews several current issues that are considered worthy of note for the histologic diagnosis of soft tissue sarcomas. PMID- 2096591 TI - Epithelial cell nodules developing in the cecum of irradiated mice. Some comparisons with jejunal nodules. AB - A method for producing macroscopic epithelial nodules was developed in order to investigate the properties of epithelial stem cells in the large intestine of mice. The cecum was exteriorized and exposed to various doses of X-ray radiation. Numbers of nodules subsequently developing were counted and plotted against radiation dose. From the logarithmic regression line, the susceptibility to irradiation of nodule-forming stem cells (NFSC) was determined. The susceptibility of cecal NFSC was comparable to the value reported for jejunal NFSC. Mice of (C57BL/6 x DS) F1-Pgk-1b/Pgk-1a that carried X-chromosome inactivation mosaicism for the phosphoglycerate kinase gene were used for examination of nodule clonality. Most cecal nodules contained only 1 type of phosphoglycerate kinase, suggesting a monoclonal origin of the nodules. Histochemical studies showed the presence of absorptive epithelial, goblet and entero-endocrine cells in 17-day-old nodules, implying multipotentiality of the NFSC. In spite of these similarities between cecal and jejunal NFSC, the macroscopic appearance of cecal nodules was quite different from that of jejunal nodules. Only crypt-like structures were observed in the former, whereas both crypt-like and villus-like structures were present in the latter. A comparison between cecal and jejunal nodules may be useful for understanding the morphogenesis of the intestinal mucosa. PMID- 2096592 TI - Biliary sludge and microcalculi in intrahepatic bile ducts. Morphologic and X-ray microanalytical observations in 18 among 1,179 consecutively autopsied livers. AB - To clarify the morphology and pathogenesis of intrahepatic calculi in the incipient stage, we examined biliary sludge and microcalculi in intrahepatic bile ducts by morphologic and X-ray microanalytical methods in 18 (1.5%) among 1,179 autopsied livers. The hepatobiliary conditions of these 18 livers were intra- and extrahepatic biliary obstruction in 14 cases, hepatic fibrosis in three cases, and cirrhosis with hepatocellular carcinoma in the remaining one. Grossly, brown pigmented microcalculi were observed floating in biliary sludge. Microscopically, the biliary sludge was composed of mucin, fibrinous materials, desquamated epithelial cells and a few bilirubin granules. The microcalculi were embedded in the sludge and consisted of mucin and precipitates of bilirubin with a granular, lamellar or amorphous appearance. Bacterial colonies were recognized in both the sludge and microcalculi in all but three cases. Intrahepatic bile ducts harboring sludge and microcalculi showed a minimal to moderate degree of glandular proliferation with mucin production. X-ray microanalysis disclosed that the sludge contained little calcium ion, whereas microcalculi were calcium-rich. These findings suggest that biliary obstruction, bacterial infection and mucin hypersecretion play an important role in the formation of intrahepatic biliary sludge and microcalculi, and that sludge is causally related to the formation of intrahepatic microcalculi. Intrahepatic microcalculi and biliary sludge may represent a pathogenetic sequence in the early stage of calcium bilirubinate hepatolithiasis. PMID- 2096593 TI - Leukocytic fragments in blood smears. AB - We retrospectively reviewed blood smears from patients with septic shock and/or disseminated intravascular coagulation (DIC) in order to determine whether the appearance of leukocytic fragments on blood smears has any clinical significance. Leukocytic fragments were seen in six of twelve cases with septic shock but in none of three cases of DIC without sepsis. All six cases with leukocytic fragments also showed fragmented erythrocytes. The fact that five of these six cases died and that four were dead within two days after the leukocytic fragments were noted may indicate that this appearance heralds a severe and terminal condition of sepsis. Although the exact reason for the appearance of these fragments is unclear, it seems to be related either to mechanical shearing through microangiopathic fibrin strands, which may also cause erythrocytic fragments, or to a complex alteration in the cell membrane due to bacteria, endotoxin, or other factors. We would like to stress that the presence of leukocytic fragments on blood smears provides an important clue to the patient's prognosis. PMID- 2096595 TI - Aggressive angiomyxoma of the vulva. Report of a case. AB - A case of aggressive angiomyxoma of the vulva is reported. A 43-year-old woman presented initially in 1987 with a left vulvar mass which clinically was thought to be a lipoma or a Bartholin gland cyst. Local excision was performed after a 27 month follow-up without any change in size. The resected tumor measured 2.7 x 2.0 x 2.0 cm and had a smooth, glistening and myxoid cut surface. Histologically, the lesion was composed of spindle-shaped or stellate neoplastic cells, which were loosely textured in the fibromyxoid matrix, and a prominent vascular component characterized by randomly distributed vascular channels of variable caliber. Immunohistochemically, the tumor cells were positive for vimentin, but not for desmin and myosin. The fine structure of the neoplastic cells was compatible with that of fibroblasts rather than myofibroblasts. These findings suggest the fibroblastic differentiation of this tumor. The patient is currently well with no evidence of recurrence, 7 months after excision of the tumor. PMID- 2096594 TI - A case of epidural granulocytic sarcoma preceding acute leukemia. AB - A 20-year-old male developed both coccygeal and leg pain and followed by rectocystic disturbance. Disc herniation between L5 and S was suspected and laminectomy was performed. At surgery, an easily curretable tumor occupied the epidural space from L5 to the end of the sacrum. In part, the tumor spread out of the vertebral canal and invaded the surrounding muscle tissue. This muscle tissue and part of the lamina were checked histologically. Initial blood analysis revealed 5% blast-like cells, but failed to confirm them as leukemic cells. Histologically, the tumor cells had round or oval nuclei with large nucleoli and scanty cytoplasm without granulocytic differentiation. Malignant lymphoma or Ewing's sarcoma was initially suspected, but the definite diagnosis was uncertain. Immunohistochemical staining with the PAP method and enzyme histochemistry revealed that the tumor cells were positive for lysozyme and naphthol ASD chloracetate esterase. Thus, granulocytic sarcoma was finally diagnosed. Electron microscopic findings supported this diagnosis. Subsequent karyotyping of bone marrow cells revealed 8; 21 translocation, thus the final diagnosis of this patient was myelodysplastic syndrome, refractory anemia with excess blast cells in transformation or acute myelogenous leukemia, M2, by the FAB classification. PMID- 2096596 TI - Pigmented dermatofibrosarcoma protuberans (Bednar tumor). An autopsy case with systemic metastasis. AB - An autopsy case of pigmented dermatofibrosarcoma protuberans (Bednar tumor) with systemic metastasis is reported. No previous example of this tumor showing widespread metastasis has been reported in the literature. The patient, a 45-year old man, developed a tumor on the right upper arm. The tumor recurred twice and metastasized to other parts of the skin, lungs and brain during the 8-year clinical course. The primary tumor contained melanin-laden tumor cells and showed a storiform growth pattern. Autopsy confirmed multiple metastatic lesions in the skin, lungs, brain, thyroid, pancreas, stomach, small intestine and thigh muscles. The recurrent and metastatic tumors lacked both melanin production and the storiform arrangement, and instead revealed "fibro-sarcomatous" change with a herring-bone or interlacing pattern of growth. PMID- 2096597 TI - In vivo and in vitro induction of 2'-5' oligoadenylate synthetase by interferon alpha in nodular non-Hodgkin's lymphoma and correlations with the clinical response. AB - We investigated the correlations between the in vivo-in vitro induction of 2'-5' oligoadenylate synthetase (2-5A synthetase) by IFN-alpha in cells isolated from patients with low-grade nodular non-Hodgkin's lymphoma (NHL) and subsequent clinical responses of these patients to IFN-alpha therapy. Eleven patients were treated daily with 9 x 10(6) U of IFN-alpha 2a in a phase II trial. After an eight week treatment, four patients achieved complete remission, one a partial response, one a minor response, and five failed to respond. Basal levels of 2-5A synthetase in lymph node tumor B cells and peripheral blood mononuclear cells (PBMC) isolated before therapy differed from patient to patient and were significantly lower than in PBMC from healthy donors (P less than 0.03). In vivo single injections of 9 x 10(6) U IFN-alpha 2a induced the 2-5A synthetase in PBMC from all patients to various degrees without quantitative relation to the clinical responses. Injection of a tenfold lower dose resulted in effects of similar extent in most cases. In vitro, IFN-alpha 2a induced the 2-5A synthetase in lymph node tumor B cells isolated before therapy, and the degree of induction was significantly higher in patients who proved to respond to therapy than in patients who displayed no or minor responses (P less than 0.013). This indicates that, in nodular NHL, the 2-5A synthetase assay may have some predictive value for responsiveness to IFN-alpha therapy. PMID- 2096598 TI - Low level toxicity and antitumor activity of butyric mono- and polyester monosaccharide derivates in mice. AB - This study compares the antitumor activity of five mono- and polyesters of n butyric acid derived from monosaccharides in the murine model of Crocker 180 TG Sarcoma. Tumor incidence at ten days, mean survival time and final survival rate were significantly affected in all cases. Combined treatment by butyric esters, alpha/beta interferon (IFN) and/or Corynebacterium parvum used as immunestimulator improved the antitumor protection. Studies of acute toxicity in mice, performed by i.p. and oral routes, showed the low toxicity of butyric esters, which were devoid of detectable side effects with no incidence on ponderal growth when administered per os in rats daily for one month. Finally, a comparative study of antitumor activity, toxicity and water-solubility of various butyric esters enabled us to select among these new molecules two isomers (carbon 3 and carbon-6 of the glucose ring substituted with n-butyric acid) derived from monoacetone glucose for further investigations of their biological mechanism in vivo and in vitro. PMID- 2096600 TI - Interferon levels in human pulmonary tumors are lower than plasma levels. AB - It is uncertain whether interferon levels in the interstitial fluid of tumors are equivalent to interferon plasma levels and we have investigated this problem in human pulmonary tumors by infusing human recombinant interferon alpha A and natural interferon Beta for about three hours before surgery. By determining the hematocrit and hemoglobin content it was possible to calculate interferon values (International Units/g wet tissue) present in the interstitial fluid of tumor and lung samples, simultaneously. In 14 patients (epidermoids, n = 9 and adenocarcinomas, n = 5) interferon levels in tumor and "normal" lung expressed as percentages of interferon plasma levels were: 9.5 +/- 3.9 and 29.8 +/- 6.9 for recombinant interferon alpha A and 3.1 +/- 0.4 and 10.1 +/- 2.4 for natural interferon Beta, respectively. Differences for both interferons are statistically significant (p less than 0.05). To our knowledge these are the first data indicating that interferon levels in pulmonary tumor interstitial fluid are markedly lower than those in normal lung although they do not clarify the main factor responsible for the decrease, they explain at least in part the negligible therapeutic activity of interferons in these tumors and emphasize the need for new approaches for improving the therapeutic index of interferons. PMID- 2096601 TI - War on the road. Prevention of the head trauma. PMID- 2096599 TI - A mannoprotein constituent of Candida albicans cooperates with antigen in the induction of a specific primary antibody response in cultures of human lymphocytes. AB - The effects of Candida albicans mannoproteins on the induction of a primary antibody response to a T-dependent antigen, sheep erythrocytes (SRBC), in cultures of human blood lymphocytes, were investigated. Two experimental systems (bulk and limiting dilution cultures) allowing the detection of both enhancing and inhibitory effects, were used. In bulk cultures, antigen alone elicited a small number of specific antibody forming cells, unless IL-2 was supplied. Addition of the fungal mannoprotein extract or of a purified constituent of it increased 5 to more than 10 times the specific response. When limiting dilution analysis was performed, we observed that: a) a similar number of specific precursor cells was induced by antigen and either IL-2 or mannoprotein; b) the plot of the number of seeded cells versus the log of the fraction of negative cultures was linear in antigen and IL-2 triggered cultures but constantly deviated from linearity when the candidal stimulant was added. Thus, more than one type of precursor cell was limiting in these cultures, and the immunoenhancing effect of mannoprotein may involve multiple cellular interactions. PMID- 2096602 TI - Dose escalation trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage. AB - The initial dose-escalating clinical trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage is reported. AT877 is characterized by its strong spasmolytic activity, its inhibition of intracellular calcium ion activity, and the inhibition of several protein kinases. A total of 113 patients (Hunt and Hess grades I to IV) who had undergone surgery within 3 days of aneurysmal rupture entered the study. Patients were divided into 5 groups according to the total daily dose of AT877: I: 20 mg; II: 40 mg; III: 60 mg; IV: 90 mg; and V: 120-180 mg. AT877 was given by intravenous infusion over 30 min two or three times a day for 14 days after surgery. Although AT877 did not completely abolish angiographic vasospasm, severe vasospasm was seen less frequently in patients given higher doses. Vasospasm was the cause of a poor clinical outcome (Glasgow outcome scale rating 3 or greater) in 19%, 7%, 9%, 8%, and 6% of the patients in groups I to V, respectively. The results indicated a favourable clinical effect of AT877 at doses above 40 mg per day. Only mild hypotension was seen, even when 60 mg of AT877 was infused over 30 min. AT877 appears to be effective in patients with subarachnoid haemorrhage. Part of its effect may be attributable to protection of the brain from ischaemic insults due to chronic cerebral vasospasm. However, the drug still needs to be evaluated in a placebo controlled double-blind trial (which is currently being carried out). PMID- 2096603 TI - Comparative study of lyophilized human dura mater and lyophilized bovine pericardium as dural substitutes in neurosurgery. AB - In a prospective, controlled randomized study either lyophilized bovine pericardium or lyophilized human dura mater have been used as a patch for the closure of the dura in 102 patients. The aim of this investigation was to compare both materials in terms of immunogenic response of the patients. The rate of post operative complications was comparably low in both groups (wound infection in 1/51 patients each). In regard of workability, thickness of the material and flexibility the pericardium patches were judged to be by far superior. Neither signs of a cellular nor of an intesified humoral response could be detected in patients who received the pericardium implants. Thus, lyophilized bovine pericardium seems to be a superior alternative for the surgical repair of dural defects. PMID- 2096605 TI - Microsurgical cordotomy in 20 patients with epi-/intradural fibrosis following operation for lumbar disc herniation. AB - Using an improved microsurgical technique, cordotomy was carried out by the cervicothoracic route in 20 patients with persistent radicular pain due to epi /intradural fibrosis following operation for lumbar disc herniation. 65% of them had good long-term results with respect to radicular pain (follow-up period 6-132 months; mean 66 months). Permanent severe motor impairment was not observed. In patients with severe pain of benign organic origin microsurgical cordotomy can be considered as a "last resort". PMID- 2096604 TI - Clinical results of the foraminotomy as described by Frykholm for the treatment of lateral cervical disc herniation. AB - During the period between 1980 and 1989, foraminotomy as described by Frykholm was performed on 230 patients suffering from lateral cervical disc herniation with exclusively radicular symptomatology. Following an average postoperative period of 3.5 years, the subjective alleviation of symptoms and the neurological symptomatology were examined in 161 patients. The mortality was nil; the morbidity was 5%, with a rapid full recovery in 4% of cases. In addition to the intra-operative findings of soft and hard disc lesions, a third group with combined findings was created. Excellent or good results were obtained in 98% of the patients with soft disc lesions, in 91% of the patients with combined findings, and in 84% of those with hard disc lesions. In 93% of the cases, there was a complete or marked improvement of paresis; in 82%, of the sensory deficits. A total of 92% of the patients were able to carry out their previous occupation to the full extent. The high efficacy of foraminotomy and the low incidence of complications described in previous studies was thereby confirmed. PMID- 2096607 TI - Exophytic gliomas of the spinal cord. AB - Intradural extramedullary glial tumours of the spinal cord are rare. We report for such tumours arising from the dorsal cord. Myelography and operative findings were almost similar to that of an intradural neurofibroma. Surgical removal had resulted in rewarding neurological recovery. One of them had a recurrence after six years and was re-explored. Anterolateral attachment near the root entry zone suggests its origin probably from the spinal cord with an exophytic growth. PMID- 2096606 TI - Metastatic spinal cord compression. Occurrence, symptoms, clinical presentations and prognosis in 398 patients with spinal cord compression. AB - We reviewed all medical records concerning patients suffering from spinal cord or cauda equina compression (SCC) secondary to cancer, in the eastern part of Denmark, from 1979 through 1985. During the period the incidence of SCC in cancer patients went up from 4.4% to 6%. However, this increase was not significant. The series comprised 398 cases, with carcinoma of the prostate (19%), lung (18%), breast (14%) and kidney (10%) accounting for 61%. The symptoms were evaluated in accordance with the patients rating of pain, motor deficits, sphincter control and paraesthesia, whereas the clinical manifestations were classified on the basis of motor deficit and bladder dysfunction. During the period preceding the diagnosis of SCC, 83% of the patients suffered from back pain, 67% from deteriorating gait and 48% had retention of the urine. In 35% of the patients there was no sphincter disturbance and 10% had normal sensory function. The outcome of treatment was estimated by changes in motor deficits and sphincter function, and depended primarily on the patients condition at the time of the diagnosis. Of the patients who were able to walk before treatment, 79% remained ambulatory, whereas only 18% of the non-ambulatory patients regained walking ability. Patients treated by decompressive laminectomy followed by radiotherapy apparently had a better response than patients treated with surgery or irradiation alone, but when the patients pre-treatment motor function was taken into account, no significant difference was observed. The study may call for a properly randomized trial with careful stratification of tumour biology, performance status and neurological deficits. PMID- 2096608 TI - Treatment of intracranial meningiomas in patients over 70 years old. AB - The neurosurgeon often finds himself in the position to having to decide whether or not to operate on an elderly patient suffering from intracranial meningioma. The decision is rarely easy and the results often disappointing. We studied 46 cases of intracranial meningioma in patients over 70 years of age, 34 patients were operated on while 12 patients were not, although both groups were subjected to long term follow-up. The operative mortality rate was 12%, a rate which increased to 20% at 3 months follow-up. Various unfavourable prognostic factors were taken into consideration, the most significant of which were: poor overall clinical condition, peritumoral oedema, the presence of diabetes mellitus and the duration of surgery. A scored grading system was created to standardize surgical indications in elderly patients with cerebral meningioma. An analysis of the grading system, when applied to patients submitted to surgery, showed that the decreased patients within 3 months of surgery had a score which varied from 7 to 12, with a mean score of 10. The surviving patients had a score averaging from 10 to 16 with a mean of 13. The patients with the lowest scores (7-9) had a 100% mortality rate while those in the upper ranges (13-16) demonstrated a mortality rate of 0%. Among the conservatively treated patients the worst outcome was seen in patients with a grading equal to or less than 12. PMID- 2096609 TI - Intracranial haemodynamics in diffuse and focal brain injuries. Evaluation with transcranial Doppler (TCD) ultrasound. AB - Intracranial haemodynamics were studied in 20 patients with diffuse and focal brain injury and experimental animals with acute intracranial hypertension by the use of TCD ultrasound. The mean flow velocity in the middle cerebral artery (MCA) commonly decreased on the side of the haematoma depending on intracranial pressure (ICP) elevation and cerebral perfusion pressure (CPP) reduction in focal injury. The decrease of the MCA flow velocity returned to normal after treatment. The flow velocities decreased bilaterally and there was no difference between the right and left side in diffuse injury. But the velocities increased in spite of ICP elevation when diffuse cerebral swelling developed. Cerebrovascular CO2 reactivity was impaired in two groups of patients with low Glasgow Coma Scale (GCS) scores. The mean velocity of the MCA and blood flow in the internal carotid artery exhibited flow patterns which changed correlatively depending on CPP reduction in experimental animals. Noninvasive study by use of TCD ultrasound can provide valuable information on variant haemodynamic phenomena in patients with diffuse and focal brain injury. PMID- 2096610 TI - Primary intraosseous meningiomas of the skull base. AB - Four cases of primary intraosseous meningiomas were seen among 373 cases of intracranial meningiomas operated upon in the Neurosurgical Clinic of the Krankenhaus Nordstadt, Hannover, FRG between January 1978 and December 1988. These 4 cases represent 1% of all intracranial meningiomas. Patients' age ranged between 21 and 66 years; 2 were females and 2 males. Presenting symptoms were localized orbital pain in 1 case, protrusion of the eye in 1 patient, pain in the orbit and forehead and protrusion of the eye in 1 patient, and peripheral facial palsy in 1 case. Symptoms lasted between 3 and 10 years. Two tumours were in the bony orbit, 1 in the bony orbit and in the frontal bone and 1 in the temporal bone. All tumours were surgically completely removed. All patients are clinically and computer tomography free of tumour 1 to 8 years after the operation. PMID- 2096611 TI - A simple method of estimating the size of large pituitary adenomas. AB - A method of measuring the volume of large pituitary adenomas is described. Measurements obtained are useful in the follow-up of patients whose tumours are treated by partial excision and radiotherapy. The method is felt also to be useful in judging whether or not a tumour should be designated a giant one thereby aiding management as well as follow-up. The method is simple and easily repeatable. PMID- 2096612 TI - Extramedullary impedance monitoring and stimulation of the spinal cord surface in percutaneous cordotomy. Technical note. AB - A needle with an insulated inner stylet has been developed for monitoring of impedance when the subarachnoid space is punctured in percutaneous cordotomy. Electric stimulation of the surface of the spinal cord with a flat-tipped electrode has been used in order to locate the optimal site for the subsequent penetration of the cord with a sharp lesion-making electrode. PMID- 2096613 TI - Eleven times recurrences of a parasagittal falxmeningioma. Case report. AB - Although meningiomas are of benign character and generally of encapsulated growth, recurrence is a known problem in treatment. The authors present the time course of a recurrent parasagittal meningioma of the falx, which recurred eleven times. Despite modern radiological diagnostic methods, which made early diagnosis of recurrent tumour possible, and the use of modern microsurgical techniques with radical tumour extirpation and followed by radiotherapy, the fatal course of benign tumour disease could not be stopped. PMID- 2096614 TI - Epidural spinal meningioma. Role of magnetic resonance in differential diagnosis. AB - A rare case of an extradurally growing spinal meningioma in an elderly woman is reported. Neuro-imaging, particularly magnetic resonance (MR), allowed to recognize the lesion, which, otherwise, could raise problems of differential diagnosis with a spinal metastasis. An emergency operation, required by a sudden neurological deterioration, was decisive in recovery of neurological deficits. In a review of the literature, extradurally growing spinal meningiomas appear to occur with a higher frequency than it is thought. Therefore, they are to be suspected when dealing with extradural spinal lesions. PMID- 2096615 TI - pH changes in front of the hydrogen generating electrode during measurements with an electrolytic hydrogen clearance sensor. PMID- 2096616 TI - Diffusion of oxygen and hydrogen gas is faster through a layer of suspended cultured C6 cells than through the medium. PMID- 2096617 TI - A method for measuring the rate of oxygen release from flowing erythrocytes in microvessels. PMID- 2096618 TI - Spatial variation of the local tissue oxygen diffusion coefficient measured in situ in the cat retina and cornea. AB - A method for measuring the local oxygen diffusion coefficient (D) in an intact tissue, in situ, in a living cat is described. Values of D were calculated from nonlinear regression analysis of the polarographic (turn-on) transients using a semi-empirical model for the retina and a theoretical one for the cornea. Two types of microelectrodes were employed: in the retina, ones with extremely short recesses; and in the cornea, bare metal needles. The local D in the cat retina was practically homogeneous with a mean of 1.97 +/- 0.11.10(-5) cm2/s, at its body temperature of 37-38 degrees C, 70.6 +/- 3.3 percent of that in isotonic saline at 37 degrees C. In the cat corneal stroma, at its normal temperature in situ of 33 degrees C, D was also virtually homogeneous with a mean of 1.19 +/- 0.20.10(-5) cm2/s, 42.8 +/- 7.3 percent of that in isotonic saline at 37 degrees C. PMID- 2096619 TI - Concentric oxygen diffusion in tissue with heterogeneous permeability and consumption. PMID- 2096621 TI - A new model for long-term investigations of cerebral oxygen supply in rats. PMID- 2096620 TI - A method to measure the diffusion coefficient of myoglobin in intact skeletal muscle cells. PMID- 2096622 TI - An experimental set-up for the blood perfused working isolated rat heart. PMID- 2096623 TI - Comparative distributions of numerical and areal indices of tissue capillarity. PMID- 2096624 TI - Facilitated transport of oxygen through hemoglobin solutions. AB - A method for quantitative analysis of hemoglobin color to estimate the oxygen saturation was developed. The method uses an image-input and -processing system composed of a 3-tube video camera and a digital image analyzer. When the system is connected to a microscope, the facilitated diffusion of oxygen in hemoglobin solutions can be observed and analyzed in a position-sensitive manner. The results led to a new transport model expressed as: J = k'CY/d, where J is the oxygen flux, C is the hemoglobin concentration, Y is the oxygen saturation of hemoglobin, d is the distance between the entrance of oxygen and the diffusion front, and k' is a constant. PMID- 2096625 TI - Carbon monoxide binding in a model of hemoglobin differs between the T and the R conformation. AB - The ratio between carbon monoxide affinity and oxygen affinity (M) is usually assumed to have a fixed value (Haldane's law), which is about 200. However, this ratio is not a constant but depends on the level of saturation (Roughton, 1970) as well as on pH (Joels and Pugh, 1958). This means that simple procedures cannot be used to calculate the combined effects of simultaneous oxygen and carbon monoxide binding. Application of our mathematical model of hemoglobin (Zock, 1987) shows that this model can account for the above-mentioned phenomena in a straightforward way. Within the context of this mathematical model of human hemoglobin the differences in shape between oxygen equilibrium curve and carbon monoxide equilibrium curve of human hemoglobin could be readily explained by assuming that the ratio between oxygen affinity and carbon monoxide affinity differs between the T and the R conformation. PMID- 2096626 TI - Carbon monoxide equilibrium curve of human umbilical cord blood. PMID- 2096627 TI - Oxygen pressures calculated in a tissue volume with parallel capillaries. PMID- 2096628 TI - Stroma-free hemoglobin solutions prepared by crystallization and ultrafiltration methods; comparison of composition and coronary vasoconstrictor potency. AB - Stroma-free hemoglobin solutions (SFHS) were prepared by the crystallization and ultrafiltration methodologies. The preparations were partially characterized with respect to their effects upon the isolated perfused rat heart. SFHS prepared by ultrafiltration is characterized by a substantially lower content of residual membrane phospholipid and a more restricted protein composition. This preparation is also essentially free of vasoconstrictor and contractility-depressant actions on the ex vivo perfused heart. In contrast, crystallization-produced SFHS is less well purified of both phospholipid and protein constituents, is likely to generate denatured protein aggregates during storage and exhibits vasoconstrictor and contractility-depressant activity which may vary significantly, from batch to batch. These findings indicate that preparative methodology based on ultrafiltration and size-exclusion, yields SFHS which is superior in these respect to that produced by a crystallization method. PMID- 2096629 TI - Oxygen transport by pyridoxylated polyhemoglobin solution. AB - Pyrodoxylated Polyhemoglobin (PolyHb-PPa) with physiological oxygen affinity (P50 27 mm Hg) was used in vitro and in vivo. The oxygen binding coefficient was 1.1 ml O2/dl/g Hb, the oxygen capacity of 8.5% PolyHb-PPa solution 9.3 ml O2/dl, Hill coefficient 1.7, Met-Hb content below 2%. Exchange transfusion of whole blood with PolyHb-PPa results in a significant, linear increase in total oxygen capacity, in contrast to exchange transfusion with asanguineous solutions. In vitro analysis of oxygen equilibrium curves of mixtures of whole blood with PolyHb-PPa, however, shows a nonlinear release of the additional blood oxygen capacity. Significant amounts of PolyHb-PPa-bound oxygen are made available only when hemodilution exceeds 25%; only at 75% hemodilution does oxygen delivery by PolyHb-PPa account for 50% of the unloaded oxygen. In vivo results after therapy for hemorrhagic shock in minipigs clearly shows the efficacy of oxygen transport by PolyHb-PPa. At 70% hemodilution, PolyHb-PPa bound oxygen was twice that of erythrocytic oxygen. Availability of this additional oxygen capacity was demonstrated by an oxygen extraction ratio of 0.40%. The utility of PolyHb-PPa solution with "normal" P50 in the therapy of moderate anemia, however, remains to be proved. PMID- 2096630 TI - Coronary capillary development following treated and untreated fetal hypoxia in the rat. PMID- 2096631 TI - Perfluorochemical oxygen carriers and ischaemic tissues. AB - This paper has outlined the potential beneficial effects of emulsified PFCs for ischaemic tissue rescue. There are very strong indications that PFC emulsions will come to play an important part in the management of the ischaemic tissues. However, the immediate goal of future studies should be to assess the value of improved formulations in this context together with analysis of their mechanism(s) of action, both alone and in combination with other therapeutic agents. PMID- 2096632 TI - Oxygen-transport fluid based on perfluorochemicals: effects on liver biochemistry. AB - The effects of (1) i.v. injection of various perfluorochemical (PFC) emulsions, (2) different fractions of the non-ionic poloxamer surfactant, Pluronic F-68, or (3) i.p. injection of component PFC oils have been studied separately in male and female rats. Injection of 10 ml/kg body wt of either Fluosol-DA 20% (F-DA) or a novel perfluorodecalin emulsion containing a C-16 oil additive in male rats increased liver weight up to 7 days later; no corresponding effect occurred in response to injection of Oxypherol (FC-43). Liver weight was also increased in female rats at 72 hr after injection of the novel emulsion but this was less pronounced than in males; liver weight in female rats was unchanged in response to injection of either F-DA or FC-43 but was 12% greater at 72 hr after injection of FDC oil. Mean liver microsomal cytochromes P-450 concentrations in male rats were increased 2-3 fold at 72 hr after injection of either FDC, F-DA or the novel emulsion; a less pronounced increase was also seen at 7 days in animals receiving the novel emulsion. No significant alterations in cytochromes activity occurred in response to injection of FTPA, FTBA, the C-16 oil, FC-43 or either commercial grade or purified pluronic solution. Liver cytochromes P-450 concentrations in female rats were unaffected by any of the experimental treatments. PMID- 2096633 TI - Perfluorochemicals and photodynamic therapy in mice. AB - The effects of pre-treatment with a novel PFC emulsion on PDT-induced tumor necrosis have been studied in mice. Injection of emulsion either 2.5 hr or 24 hr before PDT did not affect the depth of tumour necrosis. However, pre-treatment with the emulsion appeared to protect skin against photodynamic damage although the mechanism(s) and active principle(s) involved were not identified. These results suggest that there may be specific advantages in using emulsified PFCs in conjunction with PDT which may be independent of changes in tumour oxygenation. PMID- 2096634 TI - Perfluorochemicals for gas transport and improvement of cell cultures. AB - This paper has considered the effects and potential application of PFCs, their emulsions and emulsion components for regulating growth and metabolic functions of microbial, animal and plant cells in culture. PFCs will help to overcome problems encountered in conventional culture systems (e.g. limited gas supply, mechanical damage), especially where cells are grown to high density. While the commercial potential of PFCs for in vitro systems has not yet been fully exploited, the most exciting areas for future developments are in the culture of animal and plant cell lines of importance in biotechnology and medicine. PMID- 2096635 TI - The cardiovascular effects of the surfactant pluronic F68 in anesthetized dogs. AB - We tested the cardiovascular actions of the surfactant Pluronic F68 by infusing it into anesthetized dogs, in doses approximating those which would be received when Fluosol-DA were used to resuscitate moderate or severe hemorrhage (0.66 and 1.11 g/Kg). In order to alleviate the reactions to Pluronic, the surfactant was purified by treatment with activated charcoal and the dogs were pretreated with corticosterone. Pluronic F68 caused dose-dependent increments in cardiac filling pressures and in systemic and pulmonary arterial blood pressure. Heart rate and contractility remained unchanged. There was an increase in the cardiac output which was dose-dependent and unrelated to the filling pressures. Regional blood flow, as determined by radionuclide-labelled microspheres, tended to increase, but only that to the heart, kidney cortex and lung (bronchial arterial) increased to a statistically significant extent. It would appear that Pluronic F68, when purified with charcoal and after steroid prophylaxis, possesses significant hemorheologic and cardiovascular effects, indicating the need for further investigation of various purification methods and the effects of purified preparations. PMID- 2096636 TI - Oxygen supply and brain function in vivo: a multiparametric monitoring approach in the Mongolian gerbil. PMID- 2096637 TI - Dependence of cerebral capillary hematocrit on red cell flow separation at bifurcations: a computer simulation study. AB - The influence of preferential red cell entry into microvascular branches with higher flow on microvessel hematocrit distribution was studied by mathematical modeling in a reconstructed cerebrocortical microvascular network. More heterogeneous hematocrit distribution was obtained at stronger cell partitioning. Small variations in the cell separation parameter resulted in significantly different hematocrit distributions. The significance of these findings in vivo should be further evaluated. PMID- 2096638 TI - Brain ischemic depolarization and vasospasm in the Mongolian gerbil: the dependence on energy depletion levels. PMID- 2096639 TI - Carbonic anhydrase inhibition and cerebral cortical oxygenation in the rat. AB - We report here the results of our study of the carbonic anhydrase inhibitor acetazolamide on cerebral vascular and metabolic function, correlated with the effects of this agent on systemic arterial blood gases and pH. We found that the effects of acetazolamide were to increase PaO2, decrease bicarbonate ion concentration and decrease pH. While these effects were maintained for many hours after both high and low dose acetazolamide, the cerebral metabolic and vascular effects of the drug were transient. The central effects of carbonic anhydrase inhibition were consistent with increased oxygen delivery and increased tissue oxygenation. Hypoxia such as encountered at altitude, represents a challenge to the mechanisms which control blood flow in the brain. The decreased arterial oxygen content at altitude is a ventilatory drive which has the effect of 1) increasing somewhat the PaO2; 2) decreasing the PaCO2; 3) alkalinizing the blood. The decreased PaCO2 then leads to decreased CBF compounding the problem of hypoxemia. In this situation, increasing CBF helps to relieve the tissue hypoxia. This has been done by either increased inhalation of CO2 (Harvey et al., 1988) or by acetazolamide (Cain and Dunn, 1966; Forwand et al., 1968). A common feature in both treatments might be increased tissue CO2 retention (Kjallquist et al., 1969; Meyer et al., 1961) and tissue acidification (Heuser et al., 1975). The two treatments are not identical since acetazolamide seems to have additional effects on cerebral metabolism that elevated CO2 does not. Thus, we can deduce that the primary pathologic effects of acute hypoxia are due to the decreased cerebral blood flow produced by hyperventilation-induced hypocapnia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096640 TI - Platelet activating factor antagonists do not alter normal cerebral blood flow or cerebral oxygen consumption. PMID- 2096641 TI - Membrane resistance to oxygen transport inside hybridoma cells in suspension culture. AB - We have examined oxygen transport from media to a single hybridoma cell for different dissolved oxygen concentrations in media and oxygen consumption rates of cells. Intracellular oxygen concentration profiles inside the cell were simulated using currently available parameters. From the simulation, it was found that mass transfer resistance at the boundary layer does not seem to be significant. Intracellular oxygen concentrations did not differ very much from outside media concentration and the concentration gradients were relatively low for all five different media DOC's (from 0.1 to 100% air saturation). From these results, it is suspected that either hybridoma cells have better tolerance to high intracellular oxygen concentrations than normal cells or that the cell membrane has a certain mechanism for limiting oxygen transport into the cell to avoid the oxidative damage. PMID- 2096642 TI - Spinal cord repair: is tissue oxygenation an important variable? AB - We have demonstrated the reliability and feasibility of making PtO2 recordings from graft and host tissue in the injured spinal cord. The data suggest that the oxygen microenvironment of developing graft and host spinal tissue is clearly different from that found in normal spinal tissue or in transplants that have not survived or integrated well. These same constraints seem to apply to cavitation in developing grafts and poorly developed graft/host interfaces. The similarity between these findings and those from previous studies in other fetal vertebrates suggests that oxygen tensions in the spinal cord probably reflect the developmental status of the regenerating tissue. Our future studies will seek to define the relationship between anatomical development of transplant tissue and these functional (PtO2, microvascular development and tissue metabolism) indicators of graft development. These investigations should also provide a background for those later studies which seek to establish the mechanisms by which these relationships come about i.e. oxygen consumption of host/transplant tissue, blood flow to transplants, studies of glycolytic metabolism (2-DG autoradiography), etc. In this way, we can begin to understand the role of tissue metabolism in graft-mediated repair. PMID- 2096644 TI - Comparison of Tyrode and blood perfused working isolated rat hearts. PMID- 2096643 TI - Effect of tachycardia on intracellular PO2 and reserves of O2 transport in subendocardium of mouse left ventricle. AB - Intracellular PO2 (PmbO2) was determined by cryospectrophotometry in individual cardiac myocytes. The rate of progression of the freezing front was sufficient to trap the O2 distribution across the wall of the mouse left ventricle. The transmural PmbO2 distribution was uniform despite moderate tachycardia. Maximal heart rate produced a small but statistically significant transmural O2 gradient but no hypoxic myocytes in subendocardium. Reserves of diffusive as well as convective transport contribute to maintenance of aerobic metabolism during tachycardia. PMID- 2096645 TI - Response time of mitochondrial oxygen consumption following stepwise changes in cardiac energy demand. AB - We determined the speed with which mitochondrial oxygen consumption and therefore the mitochondrial ATP-synthesis adapted to changes in metabolic demand in the rabbit heart. This was done by measuring the oxygen uptake of the whole heart during a stepwise change in heart rate and correcting for the time taken by diffusion and by convective transport in the blood vessels. Data for the correction for transport time were obtained from the response of venous oxygen concentration to a stepwise change of arterial oxygen concentration. The time constant of the response of mitochondrial oxygen consumption to a step change in heart rate was found to be 4-8 s. PMID- 2096646 TI - Left ventricular surface tissue oxygen pressures determined by oxygen sensitive multiwire electrodes in pigs. PMID- 2096648 TI - Effect of local anaerobiosis on heart rate. AB - The isolated leg of a rat was connected to the body only by nerve and bone and was perfused with hypoxic Tyrode solution. Heart rate increased when metabolic parameters (PCO2, pH and lactate) reached values similar to those observed at the beginning of exercise. When the muscle was additionally stimulated by electric stimuli a significant temporal correlation between lactate and heart or respiratory rate was found. Metabolic changes caused by hypoxia and muscular contraction, in particular lactic acid, appear to act as chemical stimuli for metabolic muscle receptors participating in the generation of circulatory and respiratory responses to physical exercise. PMID- 2096647 TI - Epicardial oxygen tensions during changes in arterial PO2 in pigs. AB - Arterial hypoxemia decreased epicardial tissue PO2, measured by means of a multiwire surface electrode, as well as coronary venous PO2 and myocardial lactate extraction. Left ventricular blood flow increased, O2 delivery, O2 demand and O2 consumption of the left ventricle remained unchanged. Thus, epicardial and coronary venous PO2 indicated decreased capillary and interstitial PO2 rather than cellular hypoxia. A linear relation between mean epicardial PO2 and coronary venous PO2 proves both parameters equally effective in reflecting changes in myocardial tissue oxygenation. However, PO2 distribution curves provide additional information and epicardial PO2 is superior in models with regional changes of myocardial oxygenation. PMID- 2096649 TI - Hypoxia tolerance of coronary endothelial cells. PMID- 2096650 TI - Development of a micro transmission cell for in vivo measurement of SaO2 and Hb. PMID- 2096651 TI - Heterogeneous NADH fluorescence during post-anoxic reactive hyperemia in saline perfused rat heart. AB - In the present study epicardial NADH fluorescence photographs were taken of rat hearts during dynamic transitions of oxygen content of the myocardium. Hearts were perfused in a Langendorff set-up where it was possible to switch between low and high-pO2 perfusates. NADH fluorescence photographs were taken with a suitable fluorescence set-up and photo negatives digitized and analyzed by use of a computer. Restoration of perfusion with a high-pO2 solution resulted in a reactive hyperemic flow being established. Prior to the occlusion being lifted high NADH fluorescence was observed. Reactive hyperemic flow was associated with heterogenic NADH fluorescence patterns which diminished as control flow was restored. The patterns observed during reactive hyperemia were identical to those observed when tissue oxygen was restored by high-pO2 perfusion following high flow hypoxia achieved by low-pO2 perfusion. This study shows that heterogenic epicardial flow patterns are associated with reactive hyperemia. PMID- 2096652 TI - Myocardial oxygen supply in coronary artery disease. AB - In patients with coronary artery disease investigated during cardiac catheterisation, myocardial blood flow and myocardial oxygen consumption were significantly decreased as compared to control patients without signs of coronary artery disease. At the same time left ventricular function was impaired. In addition to regional contraction abnormalities observed in 77% of the patients, mean heart index and mean left ventricular work were diminished and mean enddiastolic pressure elevated. Among the coronary artery disease group, patients with normal blood pressure had a significantly higher left ventricular enddiastolic pressure than patients with hypertension. PMID- 2096653 TI - Arterial O2-partial pressure at positive endexpiratory pressure in hyperoxia for verification of patent foramen ovale? PMID- 2096654 TI - Tissue oxygenation of the skeletal muscle and of the heart during hemodynamic alterations in rats. AB - In the anaesthetized, open-chest rat, electrical stimulation of the sympathetic or parasympathetic nerves in the cervical area produced significant changes in the heart rate. The subsequent alterations in cardiac output and in total peripheral resistance did not alter the oxygenation of resting skeletal muscle. This means that the skeletal muscle of intact rats provided sufficient O2 to withstand shortlasting changes in hemodynamics. The increase in mean tissue PO2 on the heart after the bilateral vagotomy was the consequence of an increased perfusion due to the increased heart rate. The absence of vasoconstrictor nerve impulses after the bilateral dissection of the sympathetic cord induced a dilation of the vascular bed and therefore an increase in the tissue PO2 of the heart. PMID- 2096655 TI - Oxygen partial pressure distribution within skeletal muscle: indicator of whole body oxygen delivery in patients? AB - Simultaneously with determination of cardiac output, the distribution of oxygen partial pressure within biceps muscle was measured during and after open heart surgery in 29 patients. During extracorporeal circulation (ECC) mean muscular oxygen partial pressure (MPO2m) decreased from 25 mmHg to 14 mmHg with an increase of MPO2 values below 5 mmHg from 4% to 20%. Sustained decrease of MPO2m (greater than 1h) did not occur after ECC. Before ECC and in the postoperative period, MPO2m was lineary correlated (r = 0.85) to whole body oxygen delivery (Ox. offer) suggesting that local oxygen delivery within biceps muscle was sufficiently indicated only by systemic parameters of oxygen transport which require determination of cardiac output. Particularly with regard to relative changes, MPO2m might be used for estimation of whole body oxygen offer clinically. PMID- 2096656 TI - Tissue oxygen partial pressure distribution within the human skeletal muscle during hypercapnia. AB - In ten subjects CO2-inhalation elicited a significant increase in mean oxygen partial pressure within biceps muscle by more than 35%. Though mean oxygen partial pressure within biceps muscle increased, the distribution of oxygen partial pressure (pO2-histogram) did not change suggesting a physiological distribution of oxygen delivery within biceps muscle during hypercapnia. Buffering the blood pH did not abolish the effects of the CO2-inhalation. Therefore, a decrease of peripheral blood pH could not account for the hypercapnia induced increase of mean oxygen partial pressure within biceps muscle. Our data suggest that oxygen delivery to skeletal muscle was increased during hypercapnia, most probably due to a hypercapnia induced rise of mean capillary blood flow. PMID- 2096657 TI - Online measurements of SaO2, Ht and Hb using a micro transmission cell. AB - Recently a Micro Transmission Cell has been developed based on spectrophotometry for in vivo monitoring of SaO2 together with Hb. A study in pigs was performed to compare the cell with standard methods for measuring SaO2, Hb and Ht. The results show that the cell is capable of following the trends of SaO2, Hb and Ht at different Hb concentrations and/or O2 saturations. PMID- 2096658 TI - Muscle oxygenation and performance during low level carbon monoxide exposure. PMID- 2096659 TI - Superposition of arteriolar vasomotion waves and regulation of blood flow in skeletal muscle microcirculation. AB - In skin muscle microcirculation of Syrian hamsters, rhythmic diameter changes were studied along the arteriolar network, under normoxic conditions, at rest. A teflon coated-aluminum chamber was implanted in the dorsum skin of animals. The microcirculation was investigated using intravital microscopy technique. Vessel diameters were determined by a computer-assisted method. Power spectrum analysis of vasomotion recordings was carried out with Fast Fourier Transform and Autoregressive modelling. To determine vasomotion waveform spreading, cross spectral data (amplitude and phase) were computed, using the modified periodogram method (FFT). The arterioles were classified according to Strahler's method. Order 1 vessels (diameter: 7.50 +/- 1.16 microns) showed the highest frequency, 4 15 cycles per min, and percentage amplitude in the range 60-100%. Order 2 and 3 arterioles had intermediate frequencies, and amplitude in the range 50-100%, and 15-50%, respectively. The largest order 4 vessels (diameter: 28.97 +/- 9.55 microns) had the lowest frequency, 0.3-3 cpm, and amplitude in the range 5-20%. In most networks, cross-correlation analysis revealed two groups of frequency components. Low frequency group was propagated from order 4 and 3 vessels downstream. High frequency components were transmitted upstream from order 1 and 2 arterioles. Therefore, a complex superposition of waveforms resulted from the activity of discrete points along the microvasculature. In conclusion, rhythmic diameter changes of arterioles in skeletal muscle microcirculation regulate blood flow distribution in capillary units and control tissue oxygenation. PMID- 2096660 TI - Skeletal muscle PO2 during hypodynamic sepsis. PMID- 2096661 TI - Krypton filled flashlamp: a possible new light source for near infrared spectroscopy in vivo. AB - We have designed a reliable and flexible low cost instrument for NIR spectroscopy. A krypton filled flashlamp was used as inexpensive light source. Providing a number of suitable emission peaks in the NIR, this flashlamp is ideal for NIR spectroscopy. Application to other NIR spectroscopy systems, e.g. to CCD (Charge Coupled Device) spectrophotometers, should be possible. The introduced system was tested on human arm tissue during arterial occlusion. Results equivalent to those described by other authors could be obtained by this new technical approach. PMID- 2096662 TI - Cardiogenic oscillations of He and SF6 in expired gas in dogs. AB - Quantitative analysis of cardiogenic oscillations of He and SF6 during airway and venous loading demonstrated that both VA/Q and VA/VA inequalities were involved in the lung gas inhomogeneity producing cardiac oscillations in the expirogram. Both inequalities were coupled in such a manner that low VA/Q units had high VA/VA. The oscillations were modified in conducting airways where SF6 oscillations were attenuated more than He oscillations, probably by laminar Taylor dispersion. PMID- 2096664 TI - Assessment of stratified inhomogeneity within distal alveolar space with respect to oxygen uptake. AB - Investigations were made as to whether or not there is a limitation of oxygen transport by stratified inhomogeneity in distal alveolar gas. Experiments were performed on 2 subjects. Single breath manoeuvres were carried out with similar phases of inspiration and expiration but varying breath-hold times. The inspiratory gas contained a small amount of oxygen labeled carbon dioxide, C18O2. End-expiratory gas was analysed on its residual C18O2 partial pressure by mass spectrometry. For evaluating a stratificational conductance, compartment model analysis was applied on the breath-hold data. Stratificational conductance has been found to be higher than 553 ml.mmHg-1. min-1. When transferred to oxygen transport, this means that stratificational conductance is more than 10 times higher than oxygen diffusing capacity. It can be concluded that (i) stratified inhomogeneity in distal alveolar space does not exhibit a limiting factor of oxygen uptake in lungs, (ii) a contribution of stratificational effects to sloping alveolar plateau is expected to be of minor importance. PMID- 2096663 TI - Significance of cardiogenic mixing in dog lungs. AB - Single-breath washout of two inert gases (He and SF6) in anesthetized mechanically ventilated dogs in normal conditions with the heart beating and during reversible heart arrest revealed no effects attributable to the action of the beating heart. It is concluded that in the conditions of the experiments convective mixing by the cardiac action played an insignificant role in promoting intrapulmonary mixing and transport. PMID- 2096665 TI - Computer modeling of gas phase O2 airway transport. PMID- 2096666 TI - Oxygen transport through lung surfactant and the surfactant specific proteins. AB - At the very beginning of its migration pathway to any tissue, oxygen has to cross the lung surfactant surface layer (LSSL) and the underlying aqueous hypophase. The influence of human broncho-alveolar lavage and its lipid and specific protein components on oxygen transport were studied in vitro using sensitive electrochemical techniques. LSSL adsorbing from BAL at the dropping mercury electrode/saline interface shifted the peak potentials of oxygen reduction Ep towards more negative values. The magnitude of delta Ep was dependent on the quality of BAL. The kinetics of the oxygen transport were evaluated by measuring changes in the intensities of the reduction current. Storage of oxygen in BAL was several times higher than in saline and indicated the presence of one or more binding sites or promoters for oxygen among BAL components. The surfactant specific protein was found to be one of the binding sites (or promoters) for the oxygen. Since electron microscopic immuno-gold labelling demonstrated the presence of this protein in the LSSL, and electrochemically it proved to transport lipids from the surface layer to the subphase, it was suggested that Sp A plays the role of an oxygen carrier. PMID- 2096667 TI - An ultrastructural study of pulmonary capillary vessels in blood volume overloaded rat. AB - Blood volume overload to pulmonary capillaries was experimentally induced by arterio-venous fistula between the left common carotid artery and the left external jugular vein in 42 S-D rats. The animals were sacrificed 1,2,4,8 and 24 weeks after the operation. Just after anastomosis, blood flow index of the shunted rats was about 4 times larger than in the controls and the high value was kept throughout the experiment (p less than 0.05). The relative right ventricular weight was about 1.5 times larger than in the controls (p less than 0.05). The capillary endothelium of the alveolar septum showed nuclear enlargement, swelling of the cytoplasm with microvillous projection, and increases of pinocytotic vesicles and microfilaments. In some cases, focal edema was seen accompanied with an increase of immature stromal cells. The basement membrane showed vague in contour in edematous area, especially in the epithelial side of the alveolar septum. These changes appeared most predominantly in 2 weeks and subsided almost completely in 24 weeks. Number of endothelial nucleus of the shunted rats increased significantly in 2 and 4 weeks and was normalized in 24 weeks. The surface area and volume of the capillaries also increased significantly in 2 and 4 weeks of the shunted animals. These findings showed that the capillary endothelium reacted and then was adapted to the blood volume overload. PMID- 2096668 TI - Severity of oxygen free radical effects after ischemia and reperfusion in intestinal tissue and the influence of different drugs. AB - The influence of different drugs on ischemia induced oxygen free radical damage was examined in intestinal tissue of rats by determination of thiobarbituric acid reactive substances (TBARS). Some methodical aspects of this method were considered. Experiments were done with and without the use of polymerized stromafree hemoglobin (PHb) as an additional oxygen carrier. Reversible total occlusion of the superior mesenteric artery was performed for 90 min, reperfusion time was 2.5 hours. Despite higher O2 availability PHb did not increase the TBARS level any further. Superoxide dismutase with catalase; allopurinol; ciprofloxacin; and deferoxamine produced a highly significant reduction of TBARS, even if used together with PHb. PMID- 2096670 TI - Redistribution of local hepatic blood flow during acute bleeding and prolonged hemorrhagic hypotension studied using fluorochromed plasma proteins and surface PO2 measurements. AB - The present study was performed in order to study the development of sinusoidal blood flow heterogeneity during stepwise bleeding and during prolonged hemorrhagic hypotension. Two methods have been applied: Hepatic surface oxygen tension was measured by a multi-gold-wire-cathode. Sinusoidal perfusion patterns were demonstrated by use of fluorochromed plasma proteins. During stepwise bleeding the relative decrease of the five individual sPO2 curves showed different slopes in the same rat thus indicating a flow dependent heterogeneity. The corresponding perfusion patterns were characterized by an irregular convection front. Time dependent flow heterogeneity resulted in a perfusion pattern showing predominantly perfused sinusoids and low or no flow sinusoids, whereby the predominantly perfused sinusoids might be taken as sinusoidal shunts. It is concluded that stepwise bleeding results in a functional redistribution depending upon the degree of reduced flow, while long time induced microcirculatory changes result in sinusoidal shunt flow depending upon morphological alterations. PMID- 2096669 TI - Effect of ethanol on hepatic oxygenation: evidence of hepatic hypoxia. AB - The effects of low (1 g/kg body wt) and high doses (4 g/kg body wt) of ethanol on hepatic oxygenation in rats was investigated employing an in vivo microscopic and spectrophotometric system and also a micro oxygen electrode. The low dose of ethanol increased sinusoidal blood hemoglobin oxygenation (ISO2) at periportal regions in the liver lobule. The high dose of ethanol increased ISO2 at periportal regions, but decreased ISO2 at pericentral regions. The low dose of ethanol increased hepatic surface tissue PO2, but the high dose decreased this PO2. From these data it is concluded that the increase of hepatic blood flow, after administration of a low dose of ethanol, compensated for the increase of oxygen demand in hepatocytes but that administration of a high dose of ethanol reduced hepatic tissue oxygenation via an imbalance between delivery and demand of oxygen in pericentral regions of the liver lobule, resulting in local hypoxia in surface hepatic tissue. PMID- 2096671 TI - Support of hypoxic renal cell volume regulation by glycine. AB - PO2 declines to less than 10 mm Hg in local regions of the renal cortex. Amino acids seem to modify the hypoxic tolerance of renal cells. It was suggested that glycine may support renal function in hypoxia. Aim of the present study was to test the effect of glycine on renal cellular hypoxic tolerance. We isolated tubules of the rat kidney cortex (ITS) by collagenase treatment and measured cellular function at different levels of extracellular oxygen tensions (1, 2.5, 5, 10, 40, and 100 mm Hg) both with and without glycine in the incubation medium. No significant effects were observed in the "physiological" range at an extracellular PO2 = 100-10 mm Hg. With no glycine in the incubation medium, the outer tubular diameter of ITS rose at lower oxygen tensions, at PO2 of 1 mm Hg by about 170%, and the loss of 4 marker enzymes increased about 2-4 fold. Hypoxic lactate formation increased at extracellular oxygen tensions less than 10 mm Hg. Intracellular K+ fell in parallel to about one third of the aerobic control values. Addition of glycine to the incubation medium did not significantly change intracellular K+ or anaerobic lactate formation. In contrast, the loss of marker enzymes was significantly suppressed by glycine, lysosomal APase and mitochondrial GlDH by about 30%, cytoplasmatic LDH and brush border tau GT by about 50%. Accordingly, at PO2 = 1 mm Hg the hypoxic swelling of renal cells was suppressed in the presence of glycine by about 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096672 TI - A time resolved spectroscopic (TRS) study of migration of visual to infrared waves in brain tissue in relation to absorption of hemoproteins. PMID- 2096673 TI - Aerobic glycolysis in the retina of the crab Ocypode ryderi. AB - Our experiments on the isolated and superfused crab retina reveal that pronounced gradients for PO2 and pH exist in this tissue. The PgO2 profiles and a delayed recovery of the PgO2 after hypoxia seem to be a consequence of the oxygen consumption inside the tissue, as much as both characteristics can be abolished by impairment of electron transport in the respiratory chain after application of antimycin A. The pH profile is obviously created by a production and steady release of lactate, which could be measured in the superfusate. As this lactate release is occurring inspite of a sufficient oxygen supply and consumption, it can be concluded that this tissue performs aerobic glycolysis. PMID- 2096674 TI - An isolated perfused frog skin preparation for the study of gas exchange. PMID- 2096675 TI - Alterations in intrauterine oxygen tension during the estrous cycle in the rat and hamster and its regulation by ovarian steroid hormones: a comparative study. AB - The results indicate that marked fluctuations in oxygen availability occur during the estrous cycle in both rats and hamsters. Patterns of luminal pO2 were similar in that levels were intermediate during metestrus and maximal during diestrus. By contrast, minimal pO2 levels occurred during estrus in the rat vs. during proestrus in the hamster. The species also differed in the range of mean pO2 occurring during the cycle: approximately 5-50 mmHg in the hamster vs. 25-50 mmHg in the rat. Ovariectomy results in marked increases in luminal pO2 in both species. The increase is reduced by hormone replacement. PMID- 2096676 TI - Two-dimensional model of tissue oxygen gradients in avian growth cartilage. PMID- 2096677 TI - Effect of long-term hypoxia on oxygen transport properties of blood in pregnant guinea pigs. AB - Pregnant guinea pigs undergoing long-term hypoxia were studied and the results compared with those of control animals (pregnant, but non-hypoxic). Hypoxic animals demonstrated a decrease of O2 affinity (-7%) and an increase of O2 capacity (+35%). In addition, the HCT was found to be higher in the hypoxic group (+41%), causing haemorheological disadvantages; in a shear model study the blood of hypoxic animals had to be exposed to the gas compartment of the rheo-oxymeter up to 62% longer than that of the control group. We have postulated, that this rheological impairement is compensated, since no abnormalities in number and abortion rate of fetuses (due to a possible O2 delivery impairment) were found. Our morphological studies in fact support this opinion, showing e.g. more capillary branchings and loops and a reduction of diffusion distances between maternal and fetal blood in hypoxic guinea pig placentae. The results emphasize the importance of more detailed rheological studies in connection with other investigations for a complete description of compensatory mechanisms. PMID- 2096678 TI - Alterations of the fetal capillary bed in the guinea pig placenta following long term hypoxia. AB - Oxygen supply is an important regulator of the fetal placental capillarization. To determine the effects of long-term hypoxia on the fetal placental vessel arrangement pregnant guinea pigs were kept under hypoxic conditions (12% O2 for 45 days). Vessel casts showed a significant difference in branching and orientation of the vessels between the controls and the hypoxic animals. The hypoxic group had a less orientated capillary bed with increased branching and coiling. By light- and transmission electron microscopical studies, there was a decreased diffusion distance, a decreased diameter of the fetal capillaries, and an increased number of capillary cross-sections. These results are consistent with the hypothesis that chronic hypoxia is responsible for increased branching and coiling of the capillaries resulting in a dense network of short and narrow capillaries in the placenta. PMID- 2096679 TI - The effect of optode positioning on optical pathlength in near infrared spectroscopy of brain. PMID- 2096680 TI - Perinatal changes in hemoglobin concentration in rats. PMID- 2096681 TI - Effects of normobaric hyperoxia on hemodynamics and O2 utilization in conscious dogs. AB - Normobaric hyperoxia decreased resting whole-body O2 consumption in conscious dogs by equal (Fick) contributions from decreases in cardiac output and in the arterial-venous difference in O2 content. The decrease in O2 consumption was fully developed by 20 min, was maintained for at least 1 h, and was both reversible and reproducible. Hyperoxia also decreased heart rate, right and left ventricular work rates (and therefore, presumably myocardial O2 consumption), and pulmonary vascular resistance; and increased systemic vascular resistance and right atrial pressure. Paradoxically, hyperoxia did not change O2 delivery. This latter observation together with the decrease in O2 consumption produced a unique vertical orientation to the O2 consumption-delivery relationship induced by hyperoxia. It is concluded that hyperoxia may decrease metabolic rate and substantially alter hemodynamics, which may have important implications for understanding the metabolic regulation of oxygen utilization and for the medical and nonmedical uses of oxygen. PMID- 2096682 TI - Acid-base characteristics of steady-state exercise in rats adapted to simulated altitude. PMID- 2096683 TI - Experimental support for the theory of diffusion limitation of maximum oxygen uptake. AB - The four experiments summarized above demonstrate that there is a strong relationship between both measured muscle venous PO2 and calculated mean muscle capillary PO2 and VO2max. This is true for whole body or exercising muscle VO2max, and is seen both in isolated canine gastrocnemius and intact man. This behavior is exactly what would be expected if the diffusing properties for oxygen in skeletal muscle play a constraining role in setting maximum VO2. These data therefore support the hypothesis we advanced (Wagner, 1988a; Wagner, 1988b), that it is a quantitative integrative relationship between convective and diffusive phenomena that combine to set maximum VO2. A specific prediction of this integrative hypothesis (i.e., the non-uniqueness of VO2max as a function of convective oxygen delivery) was confirmed (Experiment 3). While at this point in time phenomena such as perfusion heterogeneity and muscle shunts cannot be quantitatively taken into account in such analyses, the remarkable concurrence between expectations of the hypothesis and experimental data continue to lend support to the basic idea that maximum VO2 is not limited by any single step of the oxygen transport pathway from atmosphere to mitochondria, but rather by the way in which each and every step combines with every other step to determine oxygen supply. PMID- 2096684 TI - O2 supply dependency in patients without hyperlactemia. PMID- 2096685 TI - The effect of epinephrine on oxygen consumption, overall energy metabolism, and substrate utilization in rats. AB - In this study the influence of epinephrine (E) on oxygen consumption, overall energy metabolism, and substrate utilization in rats has been investigated. Therefore E was infused at rates of 20, 35, and 50 ng/min for 40 min. Infusion of the solvent, saline, served as control experiment. Before, during, and after the infusion, VO2, as parameter for total metabolism, and RQ, as parameter for substrate utilization, were determined using an open circuit. In addition blood samples were taken for determination of blood glucose, plasma free fatty acids (EFA) and plasma insulin concentrations. The results show a rise in VO2 and blood glucose during infusion of E. Plasma FFA concentrations were elevated during infusion of E and of saline. Plasma insulin decreased when E was administered. RQ values were increased when E was infused at rates of 35 and 50 ng/min. The results suggest that E can influence the ratio in which glucose and FFA are utilized. This influence seems to be excerpted indirectly by influencing the availability of the substrates, rather than directly, by influencing utilization. PMID- 2096686 TI - Oxygen transport variables and muscle tissue oxygenation in critically ill patients with and without sepsis. PMID- 2096687 TI - Autoregulation remains intact during stable xenon inhalation in the baboon. AB - To test the possible effect of 32% end-tidal Xe concentration upon autoregulation, 5 baboons, Papio anubis/cynocephalus, were anesthetized/paralyzed with propranolol 0.02, diazepam 0.1, morphine sulfate 0.1, and pancuronium 0.2 (mg/(h.kg)). The animals were subjected to a servocontrolled blood infusion withdrawal program to control central aortic blood pressure (CAP). PaCO2 was held to 30 to 35 torr, with individual variation less than 3 torr by control of ventilation and by including CO2 in the Xe/O2 mixture. Three to six CBF measurements were made in each subject over the above range. In four animals the CAP was varied between 18 and 150 torr, with corresponding CBF measurements. The CAP range was extended to 196 torr in the 5th animal by IV administration of phenylephrine. Significant lowering of global blood flow did not occur above 40 torr mean CAP. While regulated flow persists to about 150 torr at the high end, there is a breakaway between 150 and 190 torr where flow increased 90%. A 4th order polynomial fit of the data has the characteristic appearance of the familiar autoregulation curve. We conclude that autoregulation is preserved even in the presence of FIXe of 32% in the breathing mixture. PMID- 2096689 TI - Analysis of oxygen transport to tissue during extreme hemodilution. PMID- 2096688 TI - Cardiovascular responses, hemodynamics and oxygen transport to tissue during moderate isovolemic hemodilution in pigs. AB - In conclusion, in contrast to many reports obtained from dogs, in pigs the rise in CO during moderate isovolemic hemodilution is, besides the increased venous return, more induced by increased work performance of the heart and less by a decreased SVR. The rise in CO did not compensate for the decrease in oxygen transport capacity. Our results confirm most of the reported findings in humans at the same stage of hemodilution. Besides changes in hemodynamics, in our study a gradual decreased oxygen affinity of hemoglobin could be observed. That the pig animal model for studying hemodilution and oxygen transport to the tissue is more appropriate than the dog model is open to discussion. PMID- 2096690 TI - Size-dependent oxygenation and energy status in multicellular tumor spheroids. AB - To evaluate interrelationships among the oxygenation, the energy status, and the development of necrosis in tumor microregions, oxygen tensions were measured with microelectrodes, and ATP distributions were determined with a quantitative imaging technique using multicellular spheroids as in vitro tumor models. The results obtained show a positive correlation between central oxygen tensions and ATP concentrations in spheroids. During spheroid growth, both quantities decrease from rather high values to recordings close to or at the background level within similar ranges of spheroid size. Since the emergence of central necroses precedes this drop in energy-rich phosphate, the data may suggest that energy metabolism is not directly involved in the development of necrosis in the spheroids investigated. PMID- 2096691 TI - Blood flow, oxygen consumption and tissue oxygenation of human tumors. AB - The objective of this article was to summarize current knowledge of blood flow and oxygen supply to human tumors, parameters which go hand in hand, and in turn critically determine the cellular metabolic microenvironment of human malignancies. A compilation of available data on blood flow, oxygen supply, and tissue oxygen distribution in human tumors is presented. Though data on human tumors in situ are scarce and there may be significant errors associated with the techniques used for measurements, experimental evidence is provided for the existence of a compromised and anisotropic blood supply to many tumors. Comparable to rodent tumors, O2-depleted areas develop in human malignancies which coincide with nutrient and energy deprivation, and with a hostile metabolic microenvironment. Significant variations in these relevant parameters have to be expected between different locations within the same tumor, at the same location at different times, and between individual tumors of the same grading and staging. PMID- 2096692 TI - Interaction of oxygen partial pressure and energy metabolism with the relaxation rate of inorganic phosphate: a 31P NMR study. PMID- 2096694 TI - Biochemistry, molecular biology, and physiology of phospholipase A2 and its regulatory factors. PMID- 2096693 TI - Phospholipases, enzymes that share a substrate class. AB - Considerable work has gone into the study of PLs since the first suggestions of their existence nearly a century ago. This work has intensified enormously since the mid-1970s when their role in signal-coupling mechanisms and in pathophysiology was recognized. While much has been done to understand this diverse group of enzymes at the molecular and mechanistic levels, the discovery of new PLs has far outstripped our capacity to study them in sufficient detail to appreciate what makes each unique while perhaps having some common mechanisms of action and regulation. One would almost plead: No new PLs - Let us study those at hand! That is not the case in our field and the discovery of new PLs will continue. It is important, however, that an understanding be gained of these enzymes at the molecular level, how they interact with their substrates, and how regulatory factors can target the function of PLs in situ. PMID- 2096695 TI - Antiflammins inhibit synthesis of platelet-activating factor and intradermal inflammatory reactions. PMID- 2096696 TI - Comparative anatomy of phospholipase A2 structures. PMID- 2096697 TI - Activation of phospholipase A2 in rheumatoid arthritis. PMID- 2096698 TI - Soluble phospholipase A2 in human pathology: clinical-laboratory interface. PMID- 2096699 TI - A novel bifunctional mechanism of surface recognition by phospholipase A2. PMID- 2096700 TI - Activation, aggregation, inhibition and the mechanism of phospholipase A2. PMID- 2096701 TI - Probing the mechanism of pancreatic phospholipase A2 with the aid of recombinant DNA techniques. PMID- 2096702 TI - Molecular aspects of phospholipase A2 activation. PMID- 2096703 TI - [Roentgencephalometric evaluation of inclination and the position of incisors in orthodontic malocclusions and normal occlusion]. AB - The aims of the study were: --to determine sagittal differences in the position and inclination of incisors in defined orthodontic anomalies as compared to eugnathic occlusion; --to assess the importance of variable interrelationships for the evaluation of incisor orientation; and --to describe the distribution of compatibility of all linear and angular assessments of incisor orientation studied in relation to both jaws, direction of deviation and type of malocclusion. A sample of 436 roentgenograms taken in subjects of both sexes aged 10-18 years (180 with eugnathic occlusion and 256 with orthodontic anomalies) were analyzed. Five dentoalveolar variables were observed. Use of the 3 degrees = 1 mm principle allowed the inclination and position of incisors to be compared. The following conclusions were reached: --as compared to eugnathic subjects, dentoalveolar variables were changed in defined orthodontic malocclusions with clear differentiation according to type of anomaly; --a significant relationship was found for most variables used to assess the position and inclination of incisors; --a complete compatibility between the position and inclination was recorded in 16.7% and 15.7% of cases in the maxilla and mandible, respectively; - compatibility between the inclination and position was highest in subjects with eugnathic occlusion; and --inclination and position of incisors may be mutually independent or even contradirectional in one and the same subject, necessitating separate analytical evaluation. PMID- 2096704 TI - [Antibody titer in saliva and serum of experimental animals]. AB - This paper reveals the antibody titer of plaque microorganisms in experimental gingivitis rats of differents ages and immunization. Before sacrificing experimental animals status of gingival tissue was assessed. Further on speciments of saliva and serum were taken for antibody titer measurements. None of the young rats developed gingivitis during experiment, where as the adult immunized rats bled on probing. Low values of antibodys point out the absence of intensive synthesis of specific antibodys in saliva upon the antigen stimulation of plaque maicroorganisms. Serum antibody titers were low in young rats, moderate in adult, and high in adult immunized rats. These results indicate that adult rats react stronger to plaque antigents than young rats and that previous contact with the antigens increases the reaction. PMID- 2096705 TI - [Prevention of infection transfer in dentistry]. AB - Dental team and dentist's office should not represent an infective risk of transfer of bacterial and viral infections for patients. As the number of such infections is on an increase, we have to take additional measures of precaution besides the standard hygienic ones. We will protect ourselves by continuous use of personal protective means (gloves, masks, glasses, caps) and proper hand hygiene, and our patients by use of disposable facilities (plastic glasses, suction-pumps for saliva, injection needles, syringes, paper napkins). After each patient, all accessories and surfaces that were in contact with him should be disinfected, and the same applies to all matrices and prosthetic devices after oral testing. Efficient disinfectants should be used following the manufacturer's instructions thereby. Our offices should also be equipped with thermodisinfectors, ultrasonic cleaners and rapid autoclaves for sensitive instruments. PMID- 2096706 TI - [Frequency of apical, lateral and furcational accessory canals]. AB - Two hundred and thirty permanent roots were examined stereomicroscopically to determine the frequency of apical, lateral and furcational accessory canals. The frequency of apical accessory canals averaged 19.6% and lateral 8.3%. The furcational accessory canals were observed in 32.0% of all furcations. These findings emphasize the necessity for undertaking the meticulous disinfection and qualitative obturation of endodontic space. PMID- 2096707 TI - [Radiographic analysis of condyle position in patients with TMJ dysfunctions]. AB - Decreased joint space is one of the basical radiographic signs of joint disease and correlation with crepitus the real clinical symptom of structural joint damage. The aim of this investigation is to find out if there is any correlation between the intrajoint condyle position and joint dysfunction symptomatology, by means of TMJ tomography evaluation. Among the patients with characteristic symptoms of TMJ dysfunction examined in our Departments, a group of hundred were tomographed (Polytom--Philips-Massiot). Thirty students not showing any anamnestic or clinical symptoms formed the control group. In the evaluation of radiographic findings we accepted the static relation between condyle and glenoid fossa in the maximal intercuspal position, where the joint space was divided in three almost equal parts. The radiographic findings of the relationship between condyle and glenoid fossa in the maximal intercuspal position are presented on with the intention of establishing the most characteristic differences between the groups. The statistical elaboration has been carried out by multivariante analysis of variance. The characteristic radiographic findings in our group of patient are: --excentric condyle position, --posterior condyle displacement and - marked asymmetry. Therefore, these findings represent efficient aid in TMJ dysfunction diagnosis, and show direction for repositioning of condyle in therapy dysfunction. PMID- 2096708 TI - [Physical and psychological traumatism. Dialectic of singular tragedy and biology]. AB - A good clinical assessment and a strict hospital's organization characterized essentially by the best climate of cooperation between the different departments permits now to control and to prevent some surgical sequelae. For a long time (approximately the 50's) generalists physicians, psychiatrists, behaviourists, have been limited in diagnosis and treatment afterwards. They could not take preventive measures, because the lack or insufficient acknowledge about this area. In fact, every surgical intervention implies psychic and existential, acute or long term disorders. A briefly summarized clinical case illustrate principles for the practice. The preventive approach of the post-surgical psychic troubles concern a lot of elements related to the patient's environement: social interactions, technic cares, types of drugs, style of relation between the specialized teams and patient, social and professional support and so on... The events, even the apparently minor, have to be enough mastered into the resuscitation's setting. The most important trouble is the "post-traumatic stress disorder" (cf D.S.M. III R), or (in the european traduction) a "nevrose traumatique". It is a stress or illness of the whole existence, especially in the case of delayed subtype. The authors emphasize the notion of "second traumatism", often withdrived from social, familial and medical supports. PMID- 2096709 TI - [Cognition, memory and affect]. AB - The flow of information within the brain and the sequence of operations which process it get enriched through a twofold mediation, that of the current affective states and that of the references made to an individual life-history. Affectivity and memory are closely linked in the elaboration of action (thought acts, speech acts, behaviours) since it is especially through the mediation of affective states and emotions that the current action is both a partial reactualization of the past and one of the major determinants of future action. Whenever the processing of information derived from the present real world induces a certain affective state, the latter acts in return so as to filter, reorient and focalize the reading of the real, while it further facilitates the memorizing--and later on the recalling--of the very information that induced it. In the elaboration of the historical and affective dimensions of mental life and of the behaviours that express it, one may distinguish--within the brain--three levels of integration, organization and adaptation. It matters to know the role played by each of these functional levels. Indeed, though the latter closely interact with one another under normal conditions, various pathological processes are likely to provoke a dissociation, together with a possibly resulting functional "regression". PMID- 2096710 TI - [Communication on awakening]. AB - When Thomas and Karin come to reeducation center after intensive care unit, they appeared in the same medical conditions. However, after a four month stay at awakening center, one will awake and recover exchanges and verbal communication while the other will develop a vegetative state, classically called "chronic". Some questions flow from these two cases: What is awakening? When can we talk about awakening? Every one, according to personal practice, has a different way to approach this phase. And that is why this concept is very difficult to define. During how much time can we talk about awakening stage? From when can we consider that patient has reached a chronic vegetative state? PMID- 2096711 TI - [Intersubjective approach of traumatic coma in a rehabilitation center]. AB - Some clinical factors make coma a particullary significant time on human level: in so far as a receptivity to others exists during coma, could some residual marks of memory be found, and therefore possible desire? In other respects, after a coma why a statistical disproportion is noticed between psychotic states and depressive states? This questions expound why this research is based upon an intersubjective accompanying during the coma. Results introduces a reflection on coma, its libidinal mobilization and its signification. PMID- 2096712 TI - [What resuscites child resuscitation?]. AB - At the crossroads of the psychological and the somatic course, a symptom appears as a crisis for the patient (the child), his environment and the medical and paramedical staffs who are in contact with him. Starting concrete situations, this article describes what happens when the family is confronted with the reanimation of a child. PMID- 2096713 TI - [Psychic life and awakening from coma in neurosurgical intensive care]. AB - What is knowable concerning the lived experience and the psychopathology of patients during the border state between coma and waking? The waking up period appears divided in two parts: "apparent incommunicability" and "waking in strangeness". A pluridisciplinary follow-up seems necessary for patients beginning with the neurosurgical reanimation process. PMID- 2096714 TI - [Post-traumatic coma and pre-traumatic memory]. AB - Instead of thinking that it is impossible to enter in the internal world of a comatose patient, we are now put before a new and encouraging prospective, that of the possibility, even though minimal, of influencing the vital residual organisation of the patient and to induce him perhaps to accept again external stimulations, which previously were too intense. As loss of conscience often causes loss of memory, our intention was to examine the problem of memory loss in comatose patients after accidents. The analysis of 50 questionnaires distributed to trauma-patients awakening from a comatose state and interviews give clear indications that: 1) the patients remember absolutely nothing during the time of the coma; 2) in the majority of cases (34) the patients remember in the moment preceding the accident a clear autodestructive tendency especially if they were the cause of the accident; and 3) almost all patients (41) agree to have benefited greatly from the trauma itself and from its memory. PMID- 2096715 TI - [Neuropsychic disorders after cardiac arrest]. AB - This study reports on a group of eight patients having experienced a cardiac arrest while in the hospital. After a quick recovery from the accident they are screened for neuropsychic disorders during and up to six months after their hospitalization. These symptoms are aspecific and are similar to those encountered after any hospitalization in an intensive care unit. Only patients with coronary artery disease exposed to the risk of recurrence, remain with a feeling of insecurity partially supported by the family. PMID- 2096716 TI - [Clinical evaluation of coma states]. AB - Coma is difficult to define and the different gradings and scales (Glasgow, Liege) are practically used and usefull. The development of pre-hospital management and patient imaging make clinical evaluation in the acute phase of lesser importance. Brain death pose a problem for diagnostic, features (permanent loss of cerebral functions) and legal aspects. Loss of integrated neuronal functions with persistent brain stem activity will define persistent vegetative state. PMID- 2096717 TI - [Psychologic and human implications of intensive care and rehabilitation of severe head injuries patients]. AB - Consequences which are involved in intensive care and rehabilitation of severely head injuries patients seem to be numerous, variable in different times and different situations. However, the authors, for more than ten years, have taken care of severely injured patients from coma to socio-professional reinsertion, and so, it allowed them to concentrate their interest to that main point: it is necessary to make a place to the patient as a desiring patient, and not only as brain injured patient who needs medical care, medical knowledge and who needs be repaired. So the Psycho-Rehabilitation Unit works this way, to allow a new intra and intersubjective homeostasis, in spite of injury and sequellae. PMID- 2096718 TI - [Short- and long-term outcome of 250 patients admitted in surgical intensive care units after multiple injuries]. AB - Two hundred and fifty polytrauma patients (mean age: 30 years) had been hospitalizated in the same trauma center, along a period of two years. Hospital mortality rate was 33% (11% in the first day). The mean I.S.S. of alive patients was 25, and 35 for dead patients. Long term survey was analysed by three questionnaires (before one year, between one and two years and after two years). Answer rate was about 80%. Sixty hundred p. cent of patients worked less than one year after multiple trauma, and 80% between one and two years; 75% noted that their family life was normal less than one year after injury; 80% presented sequelae two years after; they were subjective in 60% of cases. These sequelae did not interfere with family life or work. There was no parallelism between objective sequelae and duration of work stop in one side and gravity of lesions (I.S.S.) in other side. PMID- 2096720 TI - [Intercommunication psychiatry in a burn center]. AB - The support of psychiatric disorders in a burn centre has been effected since three years, in Saint Luc Hospital (Lyon) thanks to a liaison group. One hour a week, several cases of patients are approached in this group which gathers two psychiatrists and the team dealing with burnt patients. Psychiatrists are attached to clarify the relation between people who attend and patients, to give a diagnosis and propose a strategy in front of difficulties they meet. The psychiatric care is reintegrated in the somatic support and assured by people who are daily effectively in contact with patients. This paper describes the advantages of the liaison psychiatry with regard to a direct intervention of the psychiatrist on the patient. It defines the targets these therapeutic weapon can aim and details the obtained results: for 3 years, the group has met 104 times for 241 "indirect consultations" concerning 99 different patients and count 50 good results on site and 5 specialized orientations; 10 deaths and 11 quick departures exclude 21 patients from the study; 17 cases have been stayed without continuation and 6 without any change. PMID- 2096719 TI - [Delivery and coma: where is my child?]. AB - In three cases of parturition by Caesarean during a coma (provoked by eclampsia for both of them), the resumption of the quotidian activities for the three women at the time of the return at home was comprised by disorder states and nocturnal psychomotor agitation. Investigation and psychological interviews are focused on the emptiness (of words, representations, sensibilities) which surrounded the parturition during the coma. PMID- 2096721 TI - [Round table discussion: Coma, awakening, subjective experience]. PMID- 2096722 TI - [Parent-child psychotherapeutic management in pediatric and neonatal intensive care]. AB - In spite of medical and nursing staff competence, as well as the quality of technology, paedriatric and neonatal Intensive Care Unit (I.C.U.) are still dependent on the patient for setting up diagnosis and cares guidance. Parents, by their relation with both child and staff, can amplify or reduce feelings of despair or helplessness which seems to mark the reanimation of some children. Isolating the child from his parents with the aim to reduce tensions which are supposed to be able to slow or prevent him from being cured, proved to generate troubles at term. A psychologist working in paediatrics I.C.U. is needed in difficult situations expressed by patient symptoms or the feeling of such a situation by parents or staff. Psychologic therapy of the child and his parents have been instored and performed during the whole period of stay in the I.C.U. and that whatever the age or consciousness of the child. In spite of the vicissitudes of such taking in charge, it permit to restore a necessary continuity in patient life history and his parental's relationship. PMID- 2096723 TI - [Psychotherapy of young burnt children and members their family]. AB - Severe burns, together with certain conditions of treatment, through their effect on verbal and non-verbal channels of communication, disorganise the 'tuning' process involved in early parent-child interactions. The effects risk being all the more patrhogenic since the mother is psychically incapacitated as far as her ability to mentalize the traumatic experience of the child is concerned. PMID- 2096724 TI - [Long time hospitalization in pediatric surgical intensive care units]. AB - If the great majority of children stay in intensive care unit only for few days, a small group of patients stay for a long period of time, varying from 3 months to five years or even more. The small group include two very different entities. On the one hand, newborns with a congenital malformation, often digestive e.a. with a short small intestine, need a long time parenteral nutrition. In such cases, the family disturbance, the opening of the unit to the parents, the awakening of the infant, his psychomotor and affective attainments are as many problems for the whole medical team. On the other hand, children severely injured in accidents, that occurred on public thoroughfares or in domestic house holds, most of the time are older than 3 years. These children may present important central neurologic sequelae, or other major sequelae (multiple trauma, burn injuries, hypoxic cervical spinal cord injury). Their education, activities, games, and family relations must be actively supported. Does the hospital structure, and particularly the intensive care unit, meet such requirements in very long time hospitalization? PMID- 2096725 TI - [Memory of intensive care in children. Onset of research, first results of a survey]. AB - This document presents results about research by children (3 to 10 years old) who passed in Intensive care Unit, 1 to 7 years before. This research concerns subjective experience memories, and follows from the work we drive for some years by grown-up people which showed how those experience were near from states, psychical contents, hypothesis and constructions about early child experiences that psychological and psychoanalysis literature do describe too, but also difficult or impossible to explore. This new research props up our first hypothesis with new, surprising, observations: mnesic traces, psychological, material are the same by children or grown-up. Some clinical, theoretical and therapeutical aspects may be surrounded. PMID- 2096726 TI - [Neonatal surgery: experience of a neonatal obstetrical and surgical unit]. AB - A prospective and retrospective study of the consequences of neonatal surgery started recently in a neonatal intensive care unit. After a prenatal diagnosis of a surgical malformation has been established, the importance of a meeting with parents, neonatologists and surgeons is stressed. The relationships between the family and the neonatal team were good, although sometimes the surgeons seemed to be "forgotten". The infant's pain was usually prevented. Infants were actively managed before surgery and after surgery their rhythms were better respected. PMID- 2096727 TI - [Round table discussion. The child in surgical intensive care units]. PMID- 2096728 TI - Development of analytical instruments for industry. PMID- 2096729 TI - The human genome initiative: first steps. PMID- 2096730 TI - Electrochemical studies of the interaction of metal chelates with DNA. 4. Voltammetric and electrogenerated chemiluminescent studies of the interaction of tris(2,2'-bipyridine)osmium(II) with DNA. AB - Cyclic voltammetric and electrogenerated chemiluminescent data were used to study the binding of tris(2,2'-bipyridine)-osmium(II), Os(bpy)3(2+), an electrostatic binder, to calf thymus DNA. The oxidized form of the osmium complex, Os(bpy)3(3+), has a stronger association to DNA than the reduced form, Os(bpy)3(2+), as indicated by the negative shift of E0' of the CV waves (K3+/K2+ = 3.35). The calculated binding constant, K2+, and binding site size, s, for the Os(byp)3(2+)-DNA system depended slightly on whether a mobile or a static equilibrium was assumed. In 10 mM NaCl, 10 mM Tris pH 7, K2+ = (7.3 +/- 0.4) x 10(3) M-1 and s = 3 base pairs (mobile) and K2+ = (5.0 +/- 0.2) x 10(3) M-1 and s = 3 base pairs (static). Electrogenerated chemiluminescence (ECL) was produced upon oxidation of Os(bpy)3(2+) at a Pt electrode in a solution containing 10 mM C2O4(2-) and 10 mM phosphate at pH 5. Addition of DNA caused a decrease in the emission intensity (I); a plot of I vs relative DNA concentration yielded K2+ = (6.5 +/- 0.5) x 10(3) M-1 and s = 3 base pairs. The osmium complex produced ECL when bound to the DNA molecule with an efficiency of 30% that of the unbound chelate. PMID- 2096731 TI - Homogeneous enzyme-linked binding assay for studying the interaction of lectins with carbohydrates and glycoproteins. AB - A simple and rapid homogeneous enzyme-linked binding assay method for studying lectin-carbohydrate interactions is described. The method is based on the homogeneous inhibition of appropriate enzyme-saccharide conjugates by specific carbohydrate-binding lectins. In the presence of carbohydrate structures recognized by the lectins, enzyme activity is regained in an amount of proportional to the concentration of carbohydrate. The new method can be used to rapidly assess the relative carbohydrate specificity of the various lectins and for the selective analytical detection of simple saccharides and complex glycoproteins. Indeed, when Jacalin lectin is used in conjunction with a malate dehydrogenase-galactose conjugate, selective measurement of human IgA (immunoglobulin A) at microgram per milliliter levels in less than 10 min is possible. The potential for using this analytical methodology for determining changes in the carbohydrate structure of intact recombinant glycoproteins is also discussed. PMID- 2096733 TI - Quantitative structure-retention relationship studies of odor-active aliphatic compounds with oxygen-containing functional groups. AB - High-quality regression equations (R greater than 0.996) modeling the gas chromatographic retention indices of 115 odor-active compounds on stationary phases of different polarity are generated by using the ADAPT software system. Multiple linear regression techniques are used to describe the statistical relationship between the Kovats retention indices and structure-based molecular descriptors. These descriptors encode topological, geometrical, and electronic features of the molecules. The utility of several new descriptors encoding functions of partial atomic charge and solvent accessible surface area is demonstrated. Quantitative predictions of odor threshold values for a subset of these compounds containing the alcohol functional group are also calculated by using a similar methodology. PMID- 2096732 TI - Liquid chromatographic determination of 2-thioxothiazolidine-4-carboxylic acid isolated from urine by affinity chromatography on organomercurial agarose gel. AB - Urinary 2-thioxothiazolidine-4-carboxylic acid is a useful indicator to assess the degree of occupational exposure to carbon disulfide. A new procedure is described for the isolation of this compound from urine prior to reversed-phase high-performance liquid chromatography. It is based on liquid-liquid extraction with methyl tert-butyl ether, followed by affinity chromatography on organomercurial agarose gel. 5-Carboxythiouracil is used as internal standard. The superior selectivity of affinity chromatography for the isolation of 2 thioxothiazolidine-4-carboxylic acid from urine permits an isocratic high performance liquid chromatographic analysis. The total recovery of 2.5 mg of 2 thioxothiazolidine-4-carboxylic acid/g of creatinine in spiked urine by liquid liquid extraction combined with affinity chromatography was 48.0% (SD 2.0%, n = 8). Within-run and within-day relative standard deviations averaged 4.0% (means = 2.48 mg/g of urinary creatinine, n = 9) and 6.5% (means = 1.19 mg/g of urinary creatinine, n = 15), respectively. The detection limit of the method was estimated at 0.05 mg of 2-thioxothiazolidine-4-carboxylic acid/g of urinary creatinine. The identity and spectral purity of 2-thioxothiazolidine-4-carboxylic acid detected in the urine extracts were confirmed by diode-array UV-vis detection. Typical 2-thioxothiazolidine-4-carboxylic acid levels in individual workers exposed to carbon disulfide ranged from nondetectable to 11 mg/g of urinary creatinine, several of which exceeded the generally accepted biological exposure index of 5 mg/g of urinary creatinine. PMID- 2096734 TI - Prediction of gas chromatographic retention indexes for polychlorinated dibenzofurans. AB - A model has been developed by using molecular connectivity to describe the relationship between the molecular structure of polychlorinated dibenzofurans (PCDFs) and their gas chromatographic linear temperature-programmed retention characteristics on a 30-m fused silica column coated with a DB-5 stationary phase. Model variables account for the number of chlorine atoms present, the position and the relationship on each aromatic ring, the chlorine atom interaction between the two rings, and the skeletal structure of each PCDF isomer. PMID- 2096735 TI - Spectral peak verification and recognition using a multilayered neural network. AB - The verification and recognition of peak-shaped signals in analytical data are ubiquitous scientific problems. Experimental data contain overlapping signals and noise, which make sensitive and reliable peak recognition difficult. A peak detection system based on a class of neural networks known as "multilayered perceptrons" has been created. The network was trained and evaluated with use of vapor-phase infrared spectral data. The results of varying the network architecture on system training and prediction performance along with refinement of the form of the input pattern are presented. PMID- 2096736 TI - Optical method for monitoring the concentration of general anesthetics and other small organic molecules. An example of phase transition sensing. AB - As an example of chemical sensing based on perturbations of thermal phase transitions, we have shown that phospholipids labeled with a fluorescent dye may be used to measure the concentration of general anesthetics and other small organic molecules. The emission maximum of the hydrophobic fluorescent probe Laurdan in phospholipid bilayers shifts from a wavelength of 445 nm below the main phase transition of the lipid to 480 nm above it, with an isosbestic point at approximately 475 nm. The greatest changes in intensity at the transition occur at 440 and 500 nm, so the ratio of the intensities at these two points was used as an "order parameter". The effects of variation of the liposomal preparation method on the order parameter were explored, and it was found that in mixed lipids the parameter varied nearly linearly over the physiological temperature range. Fluorometry detected changes in the order of bilayers caused by solubilization of the anesthetic isoflurane (Forane) and of ethanol. At a defined temperature, the intensity ratio measured in the presence of anesthetic decreases in a concentration-dependent manner. Immobilizing the liposomes in a hydrogel did not perturb the response of the system. This work demonstrates the potential for using lipid phase transitions in an optical sensor for monitoring anesthetics and other small nonpolar molecules. PMID- 2096737 TI - Glucose fast-response amperometric sensor based on glucose oxidase immobilized in an electropolymerized poly(o-phenylenediamine) film. AB - o-Phenylenediamine has been used for glucose oxidase (GOx) immobilization on Pt electrodes by electrochemical polymerization at +0.65 V vs SCE. By this approach the enzyme is entrapped in a strongly adherent, highly reproducible thin membrane, whose thickness is around 10 nm. This one-step procedure produces a glucose sensor with a response time less than 1 s, an active enzyme loading higher than 3 units/cm2 of electrode surface, a high sensitivity, and a sufficiently wide linear range. The glucose response shows an apparent Michaelis Menten constant, K'm = 14.2 mM, and a limiting current density, jmax of 181 microA/cm2. The product kD of partition and diffusion coefficients of glucose in the polymer film is on the order of 10(-13) cm2/s. Due to permselectivity characteristics of the membrane, the access of ascorbate, a common interfering species, to the electrode surface is blocked. To our knowledge, this represents the first report of a membrane capable, at the same time, of immobilizing GOx and rejecting ascorbate. The interesting electrode behavior can be rationalized by using an existing model predicting the amperometric response of an immobilized GOx system. PMID- 2096738 TI - Controlled-potential electrolysis of bulk solutions at a modified electrode: application to oxidations of cysteine, cystine, methionine, and thiocyanate. PMID- 2096739 TI - Nitrous oxide and infertility. AB - Our laboratory has reported changes in luteinizing hormone releasing hormone (LHRH) from the hypothalamus following nitrous oxide (N2O) exposure. LHRH augments LH release, which in turn causes ovulation. This study evaluated how N2O disrupts ovulation and the possible resulting infertility. Adult virgin female rats (N = 64) were housed with a 12 h:12 h light cycle. Daily vaginal smears were taken and only rats exhibiting two consecutive normal 4-day ovulatory cycles were used. Thirty-two rats were placed in an environmental chamber and exposed to a mix of hydrated 30% N2O and compressed air delivered at 1.6 L/min for 8 h/day for 4 days (one cycle); controls received compressed air. All rats exposed to N2O exhibited disrupted cycles following the first day of the 4-day exposure. From a group of 12 N2O-exposed rats, 11 went into constant proestrus (day of ovulatory surge) for up to 3 weeks. Control rats cycled normally. Following each exposure, eight rats were perfused, brains sectioned, and LHRH cells identified by immunocytochemistry. Eight control rats also underwent this procedure. A threefold increase in LHRH cells was noted in N2O rats. In addition, 12 rats received 30% N2O for 4 days, followed by mating with proven male breeders for 4 days, as were controls. Six of 12 N2O rats and 12 of 12 control rats gave birth. Contrary to previous reports, no significant difference was noted in litter size or weight. The constant proestrus seen after N2O exposure is due to disruption of LHRH cells in the hypothalamus (blocked LHRH release). It is this disruption of LHRH, and therefore ovulation, which results in infertility. PMID- 2096740 TI - Antinociceptive action of tricyclic antidepressant drugs in the rat. AB - The antinociceptive effects of controlled release amitriptyline, desipramine, and placebo pellets were studied over 3 weeks using the hot plate method in 45 rats. Animals treated with desipramine at total doses of 50 mg (8 mg/kg/day) and 100 mg (16 mg/kg/day) displayed analgesia for up to 48 hours compared with the matching placebo groups. Amitriptyline did not produce significant analgesia at the same doses. By 72 hours until the final evaluation period at 21 days, the antinociceptive action of desipramine was no longer evident. These results suggest that relatively small continuously released doses of desipramine produce analgesia within 24 hours in this animal model, but an apparent analgesic tolerance develops within 3 days. PMID- 2096741 TI - Noneffectiveness of midazolam on the thalamic-evoked responses in ventrobasal complex. AB - The effect of midazolam on the rat thalamic-evoked responses in ventrobasal complex following strong electrical stimulation of the upper lip was investigated. The animals received i.p. doses of 5, 10, 20 mg/kg midazolam, or physiological saline. Relative amplitudes of the large negative potentials, which were considered to be an excitation of ventrobasal cells, were not suppressed after midazolam injection. No significant differences were found in latencies of the potentials before and after administration of the drug. It is suggested that the effective sites of midazolam may not be located at a diencephalon level. PMID- 2096742 TI - A clinical trial of long-acting local anesthetics for periodontal surgery. AB - The efficacy of long-acting local anesthetics for anesthesia during periodontal surgery and for analgesia during the immediate postoperative period was evaluated. The rationale for using long-acting local anesthetics such as etidocaine and bupivacaine is that they can provide surgical anesthesia and, because of their long duration, prevent discomfort that may occur for 4-6 hours postoperatively. Two clinical trials were performed. The first enrolled patients requiring bilateral periodontal surgery. Using a matched pair design and double blind randomized study conditions, 2% lidocaine 1/100,000 epinephrine was compared with 1.5% etidocaine 1/200,000 epinephrine for periodontal surgery. The time until complete recovery and the time until pain onset were found to be longer for the etidocaine surgeries. Postoperative pain appeared more severe, and the need for oral analgesics was greater for the lidocaine surgeries. Surgeons' rating of surgical bleeding was significantly greater for the etidocaine procedures. When matched bilateral surgeries were not available, a second double blind randomized parallel trial was performed that compared 1.5% etidocaine 1/200,000 epinephrine to 0.5% bupivacaine 1/200,000 epinephrine. No significant differences were seen in the quality of anesthesia, degree of bleeding, or postoperative pain between these two long-acting anesthetics. PMID- 2096743 TI - Analysis of 526 cases of intravenous flunitrazepam sedation in dentistry. AB - Intravenous flunitrazepam sedation was evaluated in 526 dental out-patients. The sedative effect and amnesia to the local anesthetic injections was acceptable, as was the patients' evaluation of the method. Cardiorespiratory changes were minimal and venous complications extremely rare. Romberg's test performed 120 minutes after administration was normal in almost all cases. The patients' most common complaint after leaving the clinic was oral pain from the dental procedure. The results of this case series that intravenous flunitrazepam sedation is useful for dentistry. PMID- 2096746 TI - Comparison of articaine and prilocaine anesthesia by infiltration in maxillary and mandibular arches. AB - Claims that labial infiltration of the local anesthetic articaine HCl (Ultracaine DS) results in anesthesia of mandibular pulpal as well as maxillary and mandibular lingual soft tissue have never been scientifically substantiated. The aim of this investigation was to evaluate these claims, by comparing articaine to a standard anesthetic, prilocaine HCl (Citanest Forte). To investigate this, a double blind, randomized study was conducted in healthy adult volunteers. In each volunteer, the ability to induce maxillary and mandibular anesthesia following labial infiltration with articaine was compared to prilocaine given contralaterally. Anesthesia was determined by measuring sensation to electrical stimulation at the tooth, labial and lingual soft tissue for each of the 4 non carious, non-restored, canines. Results showed that mandibular canine pulpal anesthesia had a success rate of 65% for articaine and 50% for prilocaine. Success rates for palatal and lingual anesthesia averaged 5% for each agent. As determined by chi-square analysis, no statistically significant differences were found between articaine and prilocaine for any tissue at any of the 6 sites (P greater than 0.05). A time-course assessment also failed to demonstrate a difference between the two drugs. Therefore these data are not consistent with superior anesthesia efficacy being produced by articaine at any site, including the mandibular pulpal, lingual or maxillary palatal tissues, in the canine teeth studied. PMID- 2096745 TI - Utilization and mechanism of action of tricyclic antidepressants in the treatment of chronic facial pain: a review of the literature. AB - Tricyclic antidepressants show promise in the treatment of chronic facial pain. The antinociceptive activity of this class of drugs appears to be independent of any antidepressant effects. An hypothesis is proposed that tricyclics antidepressants activate a descending serotonergic (5-HT1) antinociceptive pathway which in turn influences endogenous opioids. This antinociceptive pathway appears to utilize an endogenous pain modulation system. Future studies may demonstrate the operative mechanisms of action and open understanding as to etiologic factors. PMID- 2096748 TI - Evaluation of the accuracy of non-invasive automatic blood pressure monitors. AB - Non-invasive automatic blood pressure monitors (BP-103N, DINAMAP 845XT, Finapres 2300) were compared with the auscultatory method. The blood pressure readings given by the oscillometric method (BP-103N, DINAMAP 845XT) were accurate and reproducible. Agreement with the auscultatory method was especially good for systolic pressure. For diastolic pressure readings, there was less agreement with the results of the auscultatory method. The finger arterial pressure method (Finapres 2300) occasionally displayed greater variability than the devices using the oscillometric method. PMID- 2096747 TI - Comparative trial of succinylcholine vs low dose atracurium-lidocaine combination for intubation in short outpatient procedures. AB - Despite its many disadvantages, succinylcholine is the most commonly used drug for intubation of patients for short out-patient procedure. This double blind trial compared a low dose atracurium/lidocaine combination to succinylcholine for intubation in 40 ASA1 adult patients. Low dose atracurium/lidocaine provided clinical intubating conditions at two minutes and cardiovascular stability equivalent to succinylcholine with significantly less myalgia. Spontaneous respiration was slower after low dose atracurium/lidocaine relative to succinylcholine. Low dose atracurium/lidocaine may provide an acceptable alternative to succinylcholine for intubation in short outpatient procedures. PMID- 2096749 TI - Administration of methohexital for pediatric outpatient dentistry. AB - Rectally administered methohexital is a safe, effective sedative to ameliorate the stress of the surgical experience for the uncooperative child. The rapid onset, relatively short duration, and patient acceptance of this technique make it applicable for many pediatric outpatient procedures. Induction doses of 20-30 mg/kg of a 10% methohexital solution can produce sleep in 7-8 minutes. In some situations, the rectal route of administration has advantages over more commonly used techniques. PMID- 2096744 TI - Summary of the scientific literature for pain and anxiety control in dentistry. PMID- 2096751 TI - Peripheral nerve injury during anesthesia. AB - A case is presented where a peripheral nerve injury occurred due to the pressure of a restraint buckle causing a postoperative motor and sensory deficit. Because these are iatrogenic injuries it is useful to review the mechanism of injury and means of prevention. PMID- 2096750 TI - Scavenging system developed for the Magill anesthetic circuit for use in the dental office. AB - Numerous potential problems have been associated with long term or occupational exposure to both nitrous oxide and halothane. Despite the lack of firmly established cause-and-effect relationships, particularly in humans, it would seem prudent to use techniques that minimize operator exposure. With this in mind, a scavenging system for use in both conscious sedation and general anesthetic techniques was developed which fulfills the requirements of both general dentists as well as those administering general anesthesia. This paper describes this system and its adaptation to the commonly used Magill circuit. It also briefly reviews the factors involved in potential toxicity caused by long term exposure to nitrous oxide and halothane. PMID- 2096752 TI - [Diabetic nephropathy. Prevention and early diagnosis]. PMID- 2096754 TI - [Prospective immunologic study of mothers of HIV positive children]. AB - From a cohort of 162 children born to 161 mothers belonging to risk groups for human immunodeficiency virus (HIV) infection, we have studied 32 asymptomatic HIV seropositive and 19 HIV seronegative mothers and their offspring seropositive mothers when compared with the seronegative group had lower counts of leukocytes, lymphocytes, CD4+ cells and CD4+/CD8+ ratio as well as higher IgG and IgM serum levels. The offspring from HIV seropositive mothers differed from children born to HIV seronegative mothers in having higher lymphocyte counts, serum IgG level and spontaneous in vitro IgG production. The number of lymphocytes and the IgG serum level correlated in the child HIV seropositive mother pairs. Two children born to HIV seropositive mothers had a CD4+/CD8+ ratio below 0.8. The significance of these abnormalities and its possible relationship with active HIV infection in children is at present unknown. PMID- 2096753 TI - [Meningitis caused by Haemophilus influenzae: study of 28 cases]. AB - 28 cases of Haemophilus influenzae meningitis were retrospectively treated in a children's hospital between October 1980 and March 1987. The average age was between 23 +/- 36 months, ranged between 3 months and 13 years. Eight were females and 20 males (1/2.5). Antibiograms were obtained from 14 samples (50%), 36% was resistant to ampicillin, 7% to chloramphenicol and 7% to both. All patients, with two exceptions, were treated with third generation cephalosporins. During the hospitalization period, the following complications were found: convulsions (18%), tone and/or mobility alterations (18%), hydrocephalus or transventricular echographic dilations (14%), early deafness (3%). 54% did not develop any complications and only one patient died. Considering the high proportion of cases resistant to ampicillin, chloramphenicol or both, it is suggested to evaluate cephalosporins as an alternative for the standard therapy. PMID- 2096756 TI - [Neonatal osteomyelitis. Study of a series of 35 cases]. AB - After a brief literature review, we analyze the results obtained with a retrospective study of 35 neonatal osteomyelitis diagnosed between 1-January-75 and 31-December-87. The valuated frequency was of 0.40% alive newborns. Between the antecedents, we find previous neonatal sepsis in 68% of the cases. The clinical general findings were less apparent, emphasizing among the local symptoms the pain to passive mobilization and swelling. From acute phase reactants, this study rebounds the high sensitivity of C reactive protein and globular sedimentation rate. The most frequently germ isolated was S. aureus followed by K. pneumoniae. The osteomyelitic injure was unifocal in 71% of the cases and the femur was the most probable bone to be affected. At the initial treatment we associated a beta-lactamic antibiotic with an aminoglycoside one in all cases, with surgical removal in 94%. The mortality was null, but grave arthritic sequels appeared in 14% of the patients. Finally, we propose the employance of seriated quantification of C-reactive protein in the follow-up and control of therapeutic efficiency. PMID- 2096755 TI - [The usefulness of HIV serology in the follow up of vertical transmission of AIDS]. AB - We study 37 children with mothers infected by human immunodeficiency virus type 1 (HIV-1) at birth and over the following three years. HIV-1 serology of these patients is reported, i.e., HIV-1 antigen p24 and antibodies using two commercially available enzymatic methods and Western blot. Throughout follow-up, IgG antibodies to HIV-1 showed a statistically significant tendency to decrease (p less than 0.001). After 12 months, 70% of the children lacked HIV-1 antibody banding by Western blot; this was taken to constitute a definitive criterion of lack of antibodies to HIV-1. Five children presented p24 antigenemia during the study, four persistently so. Of the patients over 18 months of age, 8 presented HIV-1 infection symptoms (30.7%), and three suffered AIDS (11.5%). PMID- 2096758 TI - [Pericentric inversion of chromosome 9. Summary of the authors' results]. AB - A review is given of our experience in the pericentric inversions of chromosome 9 (26 cases). We examine the relevance of this pericentric inversion in the phenotype of the carriers, the significance of pericentric inversions of chromosome 9 in infertility, and the occurrence of aneusomic recombinants. We also discuss the importance of pericentric inversions of chromosome 9 in the genetic counselling and their use as a family maker. PMID- 2096757 TI - [Relapses and complications of acute lymphoblastic leukemia in childhood: a review of cases]. AB - The relapses and complications happened on the 17 cases of children with acute lymphoblastic leukemia in the Hospital General de Segovia have been reviewed from November 1974 to September 1989. Those which have a higher interest because of their relevance or infrequency have been under discussion. Among the relapses the pulmonary and the testicular are singled out. We differentiate between the complications produced during the treatment and the long-term ones, pointing up varicella as an infectious complication. PMID- 2096759 TI - [Lupus nephropathy in children. Based on the authors' caseload]. AB - We studied retrospectively 12 children with lupus nephritis divided in two groups according to the treatment made. The patients in the first group received oral 6 methyl-prednisolone alone, until children in the second received too oral cyclophosphamide. At the moment of the admission, no statistical differences were seen between both groups in terms of age, sex, clinical features, renal function, laboratory values and renal pathology based on the classification of the World Health Organisation. Patients in the second group showed a significantly better evolution in mortality (p less than 0.05), improvement of proteinuria and glomerular filtration rate (p less than 0.01 and p less than 0.05 respectively) and laboratory values, without important adverse effects. It seems that the addition of cyclophosphamide in the treatment of patients with lupus nephritis is useful to improve the prognosis of the illness in our patients. PMID- 2096760 TI - [Follow up protocol of patients with hyperphenylalaninemia]. AB - The protocol of treatment and follow-up of diagnosed as hyperphenylalaninemia (4 mg/dl) by neonatal screening patients, is presented. When admission to the Reference Center for Cataluna in relation to their concentration of phenylalanin in plasma. The only infants who receive restricted in this aminoacid diet, are those with plasma concentrations greater than 10 mg/dl. PMID- 2096761 TI - [Clinical variations in Leri-Weill dyschondrosteosis]. AB - A newborn male baby and two female relative with the Leri Weill's syndrome are described. The disease is a mesomelic dwarfism with mild to moderate shortness of stature and typical radiological deformation know as Madelung's deformity. In a family in which one or more individuals have typical disease, a relative with simple Madelung's deformity would be considered as affected. PMID- 2096762 TI - [Hanhart syndrome (aglossia-adactylia syndrome). Report of 2 cases]. AB - We discuss two cases of Hanhart syndrome, diagnosed at 3 days and 4 months respectively. Minimal diagnostic criteria (micrognathia and peromelia) are reported, and various etiologic hypothesis are discussed. This syndrome includes others as: aglossia-adactylia, hypoglossia-hypodactylia, oro-acral, oro mandibular-limb-hipogenesis, ankyloglosia superior, glossopalatine ankylosis, peromelia and micrognathia. Emphasize the impossibility of prevention; the patients may die because of food aspiration, both parents an children being subsidiary of psychological support. The possibilities of logopedical treatment and prothesis of peromelic limb must be evaluated. PMID- 2096763 TI - [Degenerative encephalopathy of probable viral etiology in the course of congenital agammaglobulinemia]. PMID- 2096764 TI - [Non-calculous biliary disease in two cases of typhoid fever]. PMID- 2096766 TI - [Psittacosis in childhood: report of 4 cases]. PMID- 2096765 TI - [Ganglionic mediastinal tuberculosis with severe tracheal stenosis]. PMID- 2096768 TI - [Congenital chylous ascites. Report of a case]. PMID- 2096767 TI - [Systemic contact dermatitis caused by mercury]. PMID- 2096769 TI - [Partial trisomy 3, 22: 47, XX, +der (22) t (3; 22) (q29; q11,1) mat.: report of a case]. PMID- 2096770 TI - [Castleman's disease. Clinico-radiologic aspects]. PMID- 2096772 TI - [Cancer of the bladder]. PMID- 2096771 TI - [Cancer of the bladder: where are we?]. PMID- 2096773 TI - [Laser therapy of superficial tumors of the bladder]. AB - Based on the treatment with Nd-YAG laser of 109 superficial bladder tumors (52 initial cases and 57 recurrences), herein we report on its indications, technical aspects, and clinical advantages. In order to evaluate the difference between laser therapy and TUR, three groups were studied to compare both techniques. 1) We evaluated the incidence of tumor recurrence in 27 cases submitted to laser therapy and 26 cases submitted to TUR. At 2 years no significant differences were observed relative to tumor recurrence or progression for both groups. 2) We evaluated bladder parietal involvement for each technique. All but one of 109 cases that had been submitted to laser therapy had preserved initial bladder capacity. Biopsies performed in areas post-laser therapy (31) and post-TUR (24), and with the resector loop in 22 cases, revealed no histologic difference between both groups (replacement fibrosis and elastic fibers). 3) We evaluated the incidence of urethral stenosis after laser therapy (22) and TUR (55). Urethral stricture was significantly lower (4.5%) for those treated with laser than for those treated by TUR (16.3%). On the basis of the overall (109 cases) and the partial (study groups) results, we consider laser treatment of superficial bladder tumors to be limited to single, less than 2-3 cms, or small, multiple initial or recurrent neoformations. PMID- 2096774 TI - Intravesical bacillus Calmette-Guerin (BCG) in superficial bladder tumors. An overview. PMID- 2096775 TI - [Primary superficial bladder carcinoma. Prognostic factors for recurrence]. AB - To evaluate the risk of tumor recurrence, we have studied the prognostic significance of the clinical features and chemoprophylaxis following transurethral resection (TUR) in 155 patients with primary superficial bladder carcinoma (Ta, T1, Tis). Thiotepa, adriamycin and cisplatin instillations in the bladder were utilized. The mean follow-up was 44 months (range 6-106). Considering the first tumor recurrence as an indication of failure of chemoprophylactic therapy, thiotepa was shown to afford better control. The significance of each variable (age, sex, drug, tumor stage, grade, number and size) was determined for each individual patient relative to the risk of recurrence after TUR and prophylactic treatment and the significant variables were then subjected to multivariant analyses (multiple logistic linear regression). Tumor number, stage and the drug utilized were shown to be significant prognostic factors (p = 0.04, 0.04 and 0.008, respectively). Based on the results of the multivariant analyses, mathematical models of prediction were assigned combining the more favourable individual prognostic values. The use of the mathematical models obtained to calculate the recurrence risk for each individual patient allowed us to classify these cases as being at high, medium or low risk for tumor recurrence. PMID- 2096777 TI - [Bladder substitution surgery versus continent diversions]. AB - Continent urinary diversion and bladder replacement procedures have been developed in an attempt to improve patient quality of life. When the oncologic objective is not compromised by the choice of diversion procedure, we prefer performing bladder replacement after cystectomy. Herein we discuss the advantages and disadvantages of continent urinary diversion highlighting the standard technique (Brickner). Similarly, the different types of continent diversion procedures and their rationale are discussed. We analyzed a series of 54 cases submitted to tubular and detubularized bladder replacement procedures. The surgical techniques are described with a special focus on mortality and morbidity. The results of the present study revealed preservation of sexual function was achieved in 16%, diurnal and nocturnal continence were achieved in 99.5% and 56%, respectively, and intussusception as an antireflux mechanism was effective in 90%. All the foregoing results have prompted us to continue this approach, particularly since there is no universal diversion or replacement procedure applicable to all patients. On the contrary, the currently available surgical procedures must be selected on the basis of each individual case in order to achieve the best possible results. PMID- 2096776 TI - [Immunotherapy of urothelial neoplasms. Experimental and clinical implications of alpha interferon]. PMID- 2096778 TI - Systemic chemotherapy in the management of advanced bladder cancer. PMID- 2096779 TI - [Neoadjuvant chemotherapy (M-VAC) in invasive cancer of the bladder. Our experience]. AB - Thirty-three patients with locally advanced T2-4NxM0 muscle infiltrating bladder carcinoma were treated with M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) following TUR. Twenty-eight patients were evaluable since 4 had been receiving the foregoing treatment and 1 was being reevaluated after having undergone a partial cystectomy procedure prior to the chemotherapeutic regimen. Eighteen patients underwent radical cystectomy after neoadjuvant chemotherapy, 2 bladders could not be resected, 2 patients refused the procedure and the remaining 6 patients had a functioning bladder. Of the 28 patients, 46.42% (pCR) were pT0 (including the 6 patients with a functioning bladder, and 10.71% (pPR) were down-staged. This represents a pGR of 57.13%. Four of the 18 patients who underwent cystectomy had a higher pathologic stage evidenced by the surgical specimen than the initial finding at TUR indicating that 22.22% had been understaged. Noninvasive diagnostic methods (TUR, cytology, ultrasound, CT...) could not demonstrate the presence of tumor in those patients with preserved bladder. The cRC is similar (46.42%) and the cRP was 7.14%, giving a total cRG of 53.56%. With a mean follow-up of 13.63 months (range 5-36+), 54.54% are alive and disease-free, including the 6 patients with preserved bladder, and 21.21% are alive with locoregional recurrence or distant metastasis. Currently the mortality rate is 9.09%. The correlation of the data gleaned from the clinical response and that of the pathological condition, the possible understaging of the preserved bladders and the outcome in a series with a very short follow-up have as yet to be elucidated. PMID- 2096780 TI - [Stage T4 bladder cancer. Impact of neoadjuvant chemotherapy on T4b tumors]. AB - The present article studied the biological behaviour of T4a versus T4b tumors. Of 29 patients with T4a tumors, 24 were treated by radical cystectomy and 5 were treated by diversion alone on detecting pathologic gross adenopathies at laparotomy. Of these 10/28 (35.7%) are alive and tumor-free. Of 11 patients with T4b tumors, 7 were initially treated with systemic chemotherapy (6 M-VAC and 1 5 FU + ADM) which achieved a clinical response in 4; 1 (14.2%) was RCc. Posteriorly, all these patients underwent radical cystectomy that revealed 2 had RPp and 2 had tumor progression (N+), accounting for an RPp rate of 28.5% and tumor progression of 71.5%. Overall, with a mean follow-up of 13.3 months, only 1 patient is tumor free. The foregoing findings show the different behaviour of these two groups of patients with an incidence of tumor positive adenopathies of 48.2% and 72.7% and tumor-free survival of 35.7% and 9.0% for patients with T4a and T4b, respectively. PMID- 2096781 TI - Chemotherapy for invasive bladder cancer: facts and fallacies. PMID- 2096782 TI - Chemotherapy in advanced bladder cancer: a review with emphasis on future studies. PMID- 2096783 TI - Selection of treatment for muscle infiltrating transitional cell bladder cancer. AB - 1. Cancers of the bladder are heterogeneous. 2. A variety of surgical and radiation treatments has been useful in local tumor control. 3. Rational selection for optimal local therapy requires definition of more specific selection criteria. 4. The favorable effects of chemotherapy in patients with advanced bladder cancer warrant clinical investigation of such treatment in adjuvant and neoadjuvant settings while the search for more effective chemotherapy continues. PMID- 2096784 TI - Effect of Rift Valley fever virus on pregnant and non-pregnant local Barki ewes after artificial infection. AB - Studies were conducted into effects of Rift Valley fever virus on oestrous and vaginal cytology in non-pregnant ewes. 6 pregnant and 8 non-pregnant local Barki ewes were subcutaneously inoculated with different doses of virus isolated from Sharkia Province. Observed were irregularities in the oestrous cycle (20-28 days inoculation) and anoestrum. The anoestrum smears included large non-cornified epithelial cells with large well stains centrally located nuclei together with a large number of bacteria. Abortion and retention of placenta occurred in pregnant ewes with prolonged puerperal heat up to 70 days. Inoculation of virus was followed by thermal response. Re-isolation of virus in BHK cells was possible from aborted foetuses and placenta. PMID- 2096785 TI - [Intracellular distribution and destruction of liposomes after in vitro phagocytosis by alveolar macrophages]. AB - Electron microscopy was used to watch and monitor free as well as phagosomically incorporated multilamellar vesicles (MLV) which were considered to be signs of rapid recycling of phagosomal membranes. Close relations were found to exist between lysosomes, on the one hand, and MLV in phagosomes, on the other. The same applied to MLV and mitochondria or nuclear membranes. Destruction of MLV was highly differentiated. Hints are given in this paper on the kinetics of such processes. These results are considered to be of some relevance to the suitability of liposomes as carriers of pharmaceutical substances. PMID- 2096786 TI - [Concanavalin A binding sites on the cell membrane and other membrane structures of alveolar macrophages]. AB - Concanavalin-A points of linkage were positively detected on cell membranes of alveolar and peritoneal macrophages by means of Con-A ferritin conjugate. Quantitative conclusions were drawn from these findings with regard to the number of mannose and glucose residues per 1 micron 2 of membrane area. With different incubation periods, 15, 25, and 45 minutes, various distribution patterns of ferritin molecules were recorded. They were diffusely distributed in cytoplasma as well as on the outer nuclear membrane. Ferritin particles were identified also on vacuolar membranes and in direct contact with lysosomes. PMID- 2096787 TI - Dynamic-interaction of vitamin K and levamisole on phenylbutazone activities. AB - The results showed that co-administration of either vitamin K or levamisole along with phenylbutazone abolished the latter's anti-inflammatory and antipyretic activities and reduced its analgesic effect. Prolonged administration of phenylbutazone alone to rats for 21 days increased significantly serum glutamate oxalacetate transaminase (SGOT) activity, urea and creatinine concentrations, while it decreased with significance uric acid concentration in the serum. Vitamin K, when administered together with phenylbutazone, reduced its effect on SGOT activity and creatinine concentration. Levamisole antagonised the uricosuric effect of phenylbutazone, when both were concomitantly given. Histopathological examination of the liver of rats, given phenylbutazone alone, showed mild degenerative changes, whereas in combination with levamisole these changes were exacerbated. Kidney showed oedema, degeneration, congestion, and haemorrhage. These changes were severe in rats, given phenylbutazone alone, moderate in levamisole-treated animals, and mild in those given both drugs. Combination of levamisole with phenylbutazone not only decreased the congestion of gastric mucosa but also activated the gastric glands. PMID- 2096788 TI - [Histologic and biochemical studies on the uteri of ovariectomized gilts during the first two months of pregnancy after different hormone substitutions. 1. Changes in the structure of the placenta during pregnancy weeks 3-8 after constant high doses of progesterone and estradiol benzoate]. AB - Sixteen pregnant gilts were ovariectomised (Groups 1 and 2: 11th to 15th days of gravidity, Group 3: 19th to 22nd days of gravidity, Group 4: 34th to 45th days of gravidity). Daily intramuscular injections of 120 mg of progesterone and 250 micrograms of oestradiol benzoate were applied to them, beginning on the day of ovariectomy to preserve gravidity. All experimental animals were sacrificed between the 21st and 25th days of gravidity (Group 1) and between the 31st and 37th days (Groups 2 and 3) as well as between the 52nd and 61st days (Group 4). Living and dead embryos were numerically recorded, and histological als well as biochemical studies were conducted in all uteri. Embryo survival rates were normal, that is between 62.8 and 80 percent in Groups 1, 2, and 3, with the numbers of living embryos being 9.5, 7.5, and 8.0. Gravidity-specific uterus alterations were typical, despite constant hormone substitution. The thickness of endometrium declined with significance over the period under review. Plication was intensified, while the surface epithelium was flattened. Vascularisation increased, particularly in the subepithelial region, and the endometrial stroma became more oedematous. Full functionality was retained by the uterine glands in the period under review (increase in glandular epithelium as well as rising activity of alkaline phosphatase). Significant increase was recorded from the activity of acid phosphatase, whereas glycogen concentrations went down in the myometrium. PMID- 2096789 TI - [Histologic and biochemical studies of the uteri of ovariectomized gilts during the first two months of pregnancy after different hormone substitutions. 2. Effects of reducing the progesterone dosage on the survival rate of embryos and the structure of the placenta and the influence of oral administration of norgestrel]. AB - Studies were conducted into ovariectomised gilts in early gravidity, with the view to finding out if reduction of daily progesterone doses had an impact upon embryo survival rate and on the structure of the placenta and if experimentally induced progesterone deficit could be offset by oral administration of norgestrel, a synthetic progestagen. Embryo survival were found to drop from 80 to 26.1 percent in response to reduced progesterone dosage from 120 mg to 40 mg, average numbers of living embryos per animal being 9.6 or 3.0. Oral administration of 12 mg of norgestrel, in addition to injection of 40 mg of progesterone, enhanced the survival rate to 64.6 percent, the average number of living embryos coming to 8.9. Reduction of progesterone doses compared to animals with sufficient progesterone supply. Depressed the beginning decrease of the thickness endometrium and surface epithelium oedematisation of the endometrial stroma was mitigated, and subepithelial hyperaemia disappeared altogether. The secretory activity of uterine glands declined, and so did the endometrial activities of acid and alkaline phosphatases. Administration of norgestrel proved helpful in substantive removal of manifestations observed in the progesterone deficit group. PMID- 2096790 TI - [Histologic and biochemical studies of the uteri of ovariectomized gilts during the first two months of pregnancy after different hormone substitutions. 3. Local effects of the conceptus on the structure of the placenta and its modification by different progesterone and norgestrel administration]. AB - Optical light microscopy was used in investigations of ovariectomised gravid gilts to which progesterone doses between 120 mg and 40 mg as well as 250 micrograms of oestradiol benzoate had been daily applied to preserve gravidity, with 12 mg of norgestrel being additionally administered to some of them. These investigations were conducted for the purpose of studying locally delimited effects of conception on the placental structure. Uterus tissue was sampled from living and dead embryos (centre and sides of ampullae) as well as from uterus regions free of foetal membranes (in-between ampullae). With adequate progesterone supply, embryos were shown to clearly affect the endometrial structures. Endometrium in the centre of ampullae, with living embryos, was lower than at points without embryos. Surface epithelium was flattened, and endometrial stroma was more strongly oedematised. Strongly pronounced hyperaemia occurred to subepithelial stroma in the centre of ampullae, and uterine glandular function was unambiguously stimulated. These embryo-triggered effects were much less or no longer detectable at all under conditions of inadequate progesterone supply (40 mg/die). Administration of 12 mg of norgestrel, in addition to 40 mg/die of progesterone, enabled embryos to exercise gravidity-specific influence upon the endometrium, as in cases of sufficient progesterone supply. PMID- 2096791 TI - [Experimental udder infection with Escherichia coli. 1. The behavior of selected clinical, hematological and other parameters concerned with milk composition]. AB - Four cows with clinically intact udders in high lactation were intracisternally infected by a pathogenic field strain of Escherichia coli. Infections were induced by quarters and with time intervals. Hence, when the animals were slaughtered six hours from beginning of the experiment, epithelial samples could be collected from cisternal walls and lactiferous ducts which, by the time of sampling, had been in contact with pathogens for one, four, and six hours. Highly acute mastitis began to develop two hours from experimental infection and exhibited typical clinical symptoms, including general disorders, unambiguous alterations to the white blood count, and changes in milk composition. These changes were typical of acute toxin action on the udder quarters. Concomitant reactions of non-infected control quarters, detectable by clinical manifestations or by laboratory diagnosis, were not observed. PMID- 2096792 TI - [Experimental udder infection with Escherichia coli. 2. Morphological changes of the epithelium in the area of the glands of the milk cistern and the large milk ducts]. AB - Optical light, transmission, and scanning electron microscopy were used in investigations of epithelia in the glandular region of the milk cistern and greater lactiferous ducts and yielded the following findings, four and six hours from infection: degeneration and necrosis of epithelial cells, intraepithelial foreign cell infiltration (neutrophilic granulocytes, lymphocytes, macrophages), intra-epithelial oedema and locally delimited epithelial loss. The lesions differed by intensity in various regions, so that a distinction could be made among five froms of epithelial alterations. The epithelial cells revealed their capability of absorbing pathogenic material and storing it in cytoplasmic vacuoles. This was considered to reflect active involvement of epithelium in antibacterial defence, and consequently, to reflect the role played by epithelium as a defence barrier in the milk cistern and greater lactiferous ducts. PMID- 2096793 TI - [Experimental udder infection with Escherichia coli. 3. Morphological changes directly to subepithelially situated structures in the area of the glands of the milk cistern and the large milk ducts]. AB - Alterations were recorded from capillaries and connective tissue by means of optical light and electron microscopy in investigations of subepithelial structures, following experimental Escherichia coli infection. These alterations led to an impairment of the blood-udder barrier and thus to increased extravasation of cells (especially neutrophilic granulocytes). They were found to accumulate in subepithelial connective tissue and, eventually, to penetrate in high quantity the epithelium proper, and, consequently, to be considerably involved in alterations to the latter. PMID- 2096794 TI - [Experimental udder infections with Escherichia coli. 4. Discussion of the pathogenesis of acute mastitis]. AB - The correlations among findings obtained from experimental Escherichia coli udder infection and reported in the three previous communications are discussed in this paper. The defence capabilities elucidated included specific and unspecific activities of non-epithelial cells, primarily neutrophilic granulocytes, macrophages, lymphocytes, plasma cells, and mast cells, as well as the capability of epithelial cells proper of absorbing pathogenic material from lumens of lactiferous ducts and milk cisterns and of storing such material within intracytoplasmic vacuoles. Hence, alterations in the course of pathogenesis of acute coli mastitis were found to be of complex nature and could be properly followed up by their morphological patterns. PMID- 2096795 TI - [The dose precision of PMSG for gilts and old sows in procedures for ovulation synchronization. 2. Organometric and histometric findings after diagnostic slaughtering]. AB - An account is given in this paper of organometric and histometric findings obtained, on three farms, N, B, and D, from ovaries, uteri, and oviducts of biotechnologically treated gilts and adult sows, using differentiated PMSG doses (600, 800, and 1,000 IU on gilts and adult sows of N and B; 500, 1,000, and 1,500 IU on gilts of D). Ovulation potentials were within the biological normal in response to low dosage (with an average of 12 to 15 follicles in gilts and 17 in adult sows). The 800 IU dose caused significant stimulation, which had to be interpreted as overstimulation for PMSG-sensitive probands of N. Ovarian reaction and induced cycle should by duly considered for interpretation of histometric findings. PMID- 2096796 TI - Pathogenicity of peste des petits ruminants virus isolated from Egyptian goats in Egypt. AB - 2 Egyptian goats and Boscat rabbits were experimentally inoculated with peste des petits ruminants (PPR) local Egyptian strain (PPR, Egypt 87). The inoculated animals contracted the disease with minor clinical manifestations, accompanied by rise of neutralizing antibodies to PPR virus. Virus was isolated from ocular and nasal secretions, buffy coat, spleen, and liver. No contact infection was observed between inoculated and healthy goats. PMID- 2096797 TI - Synthesis of 3'-(4-nitroimidazol-1-yl)-2',3'-dideoxynucleosides of pyrimidine analogues and their biological evaluation against HIV. AB - Reaction of 1,5-di-O-acetyl-2,3-dideoxy-3-phthalimido-beta-D-erythro-pento-fur anose (1) with silylated pyrimidinediones 2a-c using the Lewis acid trimethylsilyl triflate as catalyst afforded nucleosides 3a-c and 4a,c which were deprotected with 33% methylamine/ethanol to give the corresponding 3 aminonucleosides 5a-c and 6. These were reacted with 1,4-dinitroimidazoles 7a,b to give the 3-imidazolyldideoxynucleosides 8a,b and 9a-f. At sub-toxic concentrations these compounds were ineffective against HIV-1. PMID- 2096799 TI - Synthesis of N-substituted 3'-amino-3'-deoxythymidines and their biological evaluation against HIV. AB - Treatment of 3'-amino-3'-deoxythymidine (1) with carboxylic acid anhydrides afforded the corresponding acylamino derivatives 2a-f. Reaction of 1 with a variety of isothiocyanates led to the corresponding thioureido derivatives 3a-i. Also, conversion of 1 into 3'-carbylamino-3'-deoxythymidine (7) is reported. The compounds 2, 3, and 8 were evaluated for their anti-HIV activity in MT-4 cells, but did not show sufficient efficacy. PMID- 2096798 TI - Syntheses of metabolites of S-carboxymethyl-L-cysteine and S-methyl-L-cysteine and of some isotopically labelled (2H, 13C) analogues. AB - The chemical syntheses of human metabolites of S-carboxymethyl-L-cysteine (3) and S-methyl-L-cysteine (12) are described. The additional preparation of some 2H- and 13C-labelled isotopomers enabled the direct evaluation of the stabilities of 3 and 12 under physiological conditions and also facilitated the unambiguous assignments of the signals in the 13C-NMR spectra of all compounds mentioned. PMID- 2096800 TI - [Airway mucociliary transport]. PMID- 2096801 TI - [Release of leukotrienes (LTC4, D4, E4, B4) from peripheral leukocytes in patients with bronchial asthma]. AB - To evaluate the pathogenetic role of leukotrienes in bronchial asthma, the levels of leukotrienes released from leukocytes stimulated by calcium ionophore A23187 were measured by the HPLC-RIA method in 32 asthmatic patients (12 infectious type, 12 non-hyposensitized atopic type, and 8 hyposensitized atopic type). The following results were obtained: 1) The level of leukotrienes released from the leukocytes of asthmatic patients were higher than those of healthy subjects, but there was no significant difference in the levels of leukotrienes between mild and moderate asthmatic patients. 2) The levels of leukotriene B4 released from the leukocytes of the infectious-type asthmatic patients were higher than those of the atopic asthmatic patients (non-hyposensitized group). There was a tendency for levels of leukotriene C4 released from the leukocytes of the infectious-type asthmatic patients to be higher than those of the atopic-type asthmatic patients. 3) The levels of peptide leukotriene released from the leukocytes of the atopic hyposensitized patients were lower than those of the patients in the atopic non hyposensitized group, but there were no significant differences in leukotriene B4 between the groups. In addition, the levels of leukotriene C4 released spontaneously from the leukocytes of the hyposensitized group of patients were lower than those in the non-hyposensitized group. 4) Though the mechanism of the efficacy of hyposensitization has not been completely clarified, the reduction of leukocyte ability to release peptide leukotrienes through immunotherapy seems to be part of this mechanism. These results suggest that leukotrienes may play some role in the pathogenesis of both atopic- and infectious-type bronchial asthma. PMID- 2096803 TI - [Cough provocation test in asthmatic children]. AB - The effects of pH and osmolarity on cough receptors were evaluated by inhalation of aqueous aerosol in 37 children with bronchial asthma. Each of 3 different pH solutions (low 1.85-3.25, neutral 6.9-7.1, high 8.0-8.4) was combined with 3 different osmolarities (hypo 0-31, iso 254-292, hyper 830-1117 mOsm/kg), and 9 solutions were prepared. To evaluate the effect of low chloride ion concentration, neutral pH and iso-osmolar solution including low chloride ion was also prepared. These aqueous aerosols were administered from a Devilbiss 646 nebulizer for 10 seconds. Coughing was induced in 28 subjects (76%) by inhalation of low pH and hyperosmolar solution, in one subject (3%) by low pH and iso osmolar, in one (3%) by low pH and hypo-osmolar, in three (8%) by neutral pH and hypo-osmolar, and in none by any of the other solutions. It was suggested that the alteration of pH or osmolarity alone could not induce coughing effectively, and that the combination of pH and osmolarity was the important factor for the induction of coughing. PMID- 2096802 TI - [Creola bodies and the eosinophil cationic protein in sputum in acute asthmatic attacks with respect to their clinical significance]. AB - Creola bodies (CrB) are characteristically present in sputa from patients with asthma. We studied the relationship among the numbers of CrB, the course of asthmatic attacks and the concentration of sputum eosinophil cationic protein (ECP). Twenty-two asthmatic attacks in 17 patients were studied. Sputum collections pulmonary function tests were made before or during treatment in patients who came to the outpatient clinic or emergency room. Smears of 100 microliters of sputum were made on glass slides and CrB were studied over the whole area of glass slide stained with Papanicolaou's stain. CrB scores were determined from the number and the size of CrB on each slide. In hospitalized patients the CrB scores, the concentrations of sputum ECP and the severity scores of asthmatic attacks were highest on the day of admission, decreasing in association with each other and returning to the baseline level in approximately 5 days. There were significant correlations among the CrB score, the concentration of sputum ECP and %FEV1.0 (p less than 0.001). The CrB score on the day of clinical appraisal significantly correlated with the number 6f days of treatment needed for remission. These results are in keeping with the hypothesis that eosinophils cause desquamation of respiratory epithelial cells resulting in prolongation of asthmatic attacks. Observation of CrB seemed to be useful as a marker of duration of asthmatic attacks. PMID- 2096804 TI - [The participation of epithelial desquamation in the increase of bronchial hyperresponsiveness after antigen challenge in patients with bronchial asthma]. AB - Bronchial hyperresponsiveness (BHR) was evaluated before and after antigen challenge in 12 patients with bronchial asthma as allergic reaction to house dust mites. Six out of the 12 showed an increase in BHR 48 hours after antigen challenge. Although there was no difference in the decrease of FEV1.0 in IAR and LAR between patients with (group A) and without (group B) the increase of BHR after antigen challenge, patients in group A expectorated a significantly larger number of clumps of respiratory epithelial cells (Creola bodies, CrB) in their sputum in both IAR and LAR. In addition, the degree of the increase of BHR significantly correlated with the CrB score, which was determined from the number and the size of CrB. These results suggest that epithelial desquamation participates in the increase of BHR after antigen challenge. The concentration of the eosinophil cationic protein (ECP) in their sputum did not change significantly in IAR and LAR compared with that before antigen challenge. There was no difference in the concentration of ECP in their sputum between the two groups either. One antigen challenge seemed to be too mild to induce an elevation of the concentration of ECP in their sputum. Judging from the fact that CrB could be observed not only at LAR but also IAR, epithelial desquamation seemed to be dependent on the degree of damage before antigen challenge rather than on the activation of eosinophils after antigen challenge. PMID- 2096805 TI - [3 cases of food-dependent exercise-induced anaphylaxis in which aspirin intake exacerbated anaphylactic symptoms]. AB - Exercise-induced anaphylaxis (EIAn) is a distinct form of physical allergy. As one of the predisposing factors of EIAn, food intake is often cited, and such cases are classified as food-dependent EIAn. Another factor reported is the administration of drugs. Recently we had 3 patients with food-dependent EIAn who showed more severe symptoms when they took aspirin orally. None of them had shown symptoms when they took aspirin alone. Symptoms were provoked only when they took aspirin for common cold, headache or toothache followed by certain foods and exercise. Two out of the 3 patients had experienced food-dependent EIAn before. However, after taking aspirin, their anaphylactic symptoms were more severe with more slight degree of exercise. Results of exercise challenge by treadmill showed that exercise alone induced an increase in plasma histamine concentrations in 2 out of the 3 patients 5 to 15 minutes after the challenge. These data suggest the possibility that our patients have an increased histamine releasability from mast cells responding to exercise, and that aspirin intake might enhance the process. PMID- 2096806 TI - [Studies on the pathogenic mechanism of beta-lactam hypersensitivity by the detection of leucocyte migration activating factor and leucocyte migration inhibitory factor]. AB - In 145 suspected cases of beta-lactam hypersensitivity, the identities of the allergenic drugs were performed by leucocyte migration inhibition test (LMIT). The involvement of cell-mediated immunity using leucocyte migration activating factor (LMAF) and leucocyte migration inhibitory factor (LMIF) was investigated for each allergic symptom. The proportion of LMIT positives was 74% of all 145 cases, and more than 70% for each allergic symptom except for anaphylactic shock, and in particular more than 90% for fever and eosinophilia. LMAF and LMIF were detected 39% and 35% of 145 cases, respectively, however LMAF was more frequently detected than LMIF in cases with hepatopathy. LMAF was more frequently detected than LMIF when the latent period (the duration of sensitization) of skin eruption or fever was less than 10 days, whereas LMIF was more frequently detected than LMAF when it was more than 10 days. The same result also was obtained at the boundary between 14 days of the latent period in hepatopathy. These results indicate that in the pathogenesis of beta-lactam hypersensitivity, cell-mediated immunity plays a major role. Both LMAF and LMIF are involved, and their production is dependent on the duration of allergenic drug-sensitization, LMAF is produced during the early period of sensitization, whereas LMIF is produced during the late period of sensitization. PMID- 2096807 TI - [A new counting method for airborne Japanese red cedar and grass pollen allergens by the immunoblotting technique]. AB - We devised a new counting method of pollen allergen particles which improved the fluorescence immunoblotting technique by Schumacher et al (1988). And by which airborne pollen allergens became visible under 10X magnifier or naked eyes. Airborne pollen allergens collected on the Burkard's sampling tape were transferred onto nitrocellulose membrane and were reacted with anti Cry j I rabbit serum or anti Lol p I rabbit serum, and then treated with alkaline phosphatase conjugated F(ab')2 anti rabbit IgG. Finally, bluish purple spots were obtained by staining with BCIP/NBT phosphatase substrate system. This technique does not require any skillful morphological observation, and is more suitable to measure the amounts of airborne pollen allergen for given pollinosis patients because total pollen allergen particles with common antigenicity are measured. In Japanese red cedar pollen counts, we could not count the spots more than 400 grains per 0.16 cm2 of the sample trapping area due to many overlapping spots. In this case, we tried to calculate the value from the ratio of bluish purple coloured area to one pollen area. However, a more suitable method for estimating the content of pollinosis caused airborne allergens may be colorimetric quantitation using densitometry and displaying the value as allergen content. PMID- 2096808 TI - Effects of N-556 on experimental allergy models in rats. AB - The oral anti-allergic effect of 1,3-bis-(2- ethoxycarbonylchromon-5-yloxy)-2 ((S)-lysyloxy)propane dihydrochloride (N-556, KY-556) was investigated. 1) N-556 (10-100 mg/kg, p.o.) inhibited dose-dependently the 48-hr homologous PCA in rats, and the duration of action was longer than that of intravenous DSCG. 2) N-556 (20 and 100 mg/kg once a day for 20 consecutive days, p.o.) tended to inhibit the histamine release from actively sensitized rat lung fragments. 3) N-556 (100 mg/kg, p.o.) showed the prolongation of survival time in the rat systemic anaphylaxis. 4) N-556 (100 mg/kg, p.o.) significantly inhibited the increased airway resistance in experimental asthma in rats. These results suggest that N 556 is a promising and orally-active pro-drug of disodium cromoglycate (DSCG) against allergic diseases. PMID- 2096809 TI - [Bronchial responsiveness to methacholine in the mouse tested by a new apparatus measuring respiratory resistance]. AB - We developed a new apparatus for the measurement of mouse respiratory resistance (Rrs) by an oscillation method. Bronchial responsiveness to methacholine was studied in mice sensitized or not with egg albumin using this apparatus. All of the sensitized mice showed clearly increased bronchial reactivity upon nasal challenge with methacholine compared to normal control mice. The lung obtained from a sensitized mouse showed remarkable contraction of the bronchial smooth muscle, submucosal edema and cell infiltration around the bronchi. These results indicate that mouse Rrs is successfully measured by our newly developed apparatus and suggested that repeated sensitization of mice with allergen render their airway hyperreactive to methacholine. PMID- 2096810 TI - Cerebral malaria--an analysis of 55 cases. AB - This study reflects the clinical pattern, diagnosis and management of cerebral malaria in 55 consecutive patients from Chittagong Hill Tracts. The predominant clinical features were: impaired consciousness with convulsion in a febrile patient with temporary residence in the endemic zone. Younger people were more prone to develop this condition. Thirty two patients (58.18%) were between 18-25 years. A high incidence of cerebral malaria was noted in blood group 'O' (37.5%) and group 'B' (33.33%). The malarial parasite count MPC was not proportional to the severity of the disease. Twenty four patients (43.63%) had malarial parasite count below 100% cumm. Anaemia (63.63%) and Jaundice (34.54%) were common, Splenomegaly (7.27%) was uncommon. Clinical features of cerebral oedema/raised intracranial pressure were not evident. CSF study was unremarkable except for raised pressure in 7 patients (12.65%). Response to intravenous quinine was satisfactory and yet the mortality was 11%. PMID- 2096811 TI - Stroke in patients having inadequate or irregular antihypertensive therapy. AB - One hundred consecutive hypertensive patients with stroke admitted to the medicine units of Dhaka Medical College Hospital were studied. The main objective was to study the extent of drug compliance and control of blood pressure in hypertensive patients who had suffered a stroke. Detailed history and clinical examinations were performed in all patients and outcome was recorded. Of the 100 patients studied there were 73(73%) males, 27 (27%) patients had no formal schooling and 53 (53%) had some education. 48 (48%) patients were from middle class and 36 (36%) were poor, 66 (66%) patients were aware that they were hypertensive though only 8 (12.9%) were taking anti-hypertensive drugs regularly. 62% of the patients had suffered from stroke within 5 years of detection of hypertension, and 15 (15%) patients died in the hospital. PMID- 2096812 TI - Multiple reuse of disposable insulin syringes in hospital. AB - In a prospective study disposable insulin syringes were repeatedly used for injecting insulin to 92 insulin-taking diabetic patients admitted in hospital with various illnesses. One separate syringe was used for each patient; the syringes were not washed or boiled and were not kept in spirit or in refrigerator during reuse. Syringes were flushed with air, needle recapped and replaced into their plastic cover. Number of injections made using one syringe was 2 to 120 (mean 31.3, SEM 2.3). For the patients' total insulin - taking period in hospital one disposable syringe per patient was enough in all but six cases. There were 2792 reinjections and incidence of infection of the injection site was zero. PMID- 2096813 TI - Smoking habit among Bangladesh Secretariat staff. AB - The paper assesses the smoking behaviour among the Bangladesh Secretariat Staff, Dhaka. The findings are based on interviewing 2008 respondents of whom 775 (38.6%) were reported to be smokers. Amongst the three categories of the respondents selected for interview, the prevalence of smoking was the highest (49%) for the respondents belonging to the lowest socio-economic group. The mean age at commencement of smoking was in the neighbourhood of 18 years. Majority of the smokers (76.5%) were motivated by their friends. Advertisement did not appear to have any influence of smoking. Nearly 17% were self motivated. Respondents' current age, level of education and employment status were found to have strong influence on smoking habit. PMID- 2096815 TI - Molecular similarities and differences between immunoglobulin and T cell receptors. PMID- 2096814 TI - A Bangladeshi family with three sisters 'Bombay' or Oh phenotype. AB - Three sisters in a same family (MIAH FAMILY) are of 'Bombay' phenotype. These being the first known female examples of 'Bombay' blood group have been detected in Bangladesh. As predicted by current theory their red cells are Le(a+b-) and their saliva do not contain any of the antigens A, B and H except Lea substance. Family studies showed that individuals with 'Bombay' or Oh phenotype may have A or B gene which are not expressed. This very particular type of blood is one of the rarest in any other parts of world except in India. Due to the presence of anti-H antibody in the plasma of Oh phenotype, when considering such patients for transfusion only blood of identical Bombay type can be safely transfused. PMID- 2096816 TI - Gene technologies for antibody engineering. PMID- 2096818 TI - Cloning for expression of immunoglobulin variable region genes and generation of variable region gene repertoires. PMID- 2096817 TI - Construction, function and immunogenicity of recombinant monoclonal antibodies. AB - Much of the interest in chimaeric antibodies stems from their presumed lack of immunogenicity in humans. We have tested this assumption using mouse models and have concluded that whilst chimaerisation can certainly lead to a reduction in the total anti-antibody response, a substantial anti-variable region response can nevertheless remain. As it therefore seems likely that determinants within the variable region lead to this anti-antibody response, we have initiated experiments to test whether it might be possible to use transgenic mice that carry human immunoglobulin gene segments in their germline configuration as a means of making a repertoire of entirely human antibodies. PMID- 2096819 TI - Recombinant monoclonal antibodies in tumor therapy. AB - The application of monoclonal antibodies (MAb) of non human origin in the treatment of human diseases is hampered by the immunogenicity of those molecules in patients. The development of molecular biology provides us with the opportunity to overcome the problem of immunogenicity and even allows the development of new immunotherapeutic approaches. These approaches use the MAb as carriers to deliver certain properties (MAb + X) to a specific site in the patient. These properties can be toxic principles like radioactivity or cytostatically active substances, enzymatic activities or specific receptor functions. In addition to the molecular biology of MAb a detailed analysis of the pharmacokinetic behaviour of molecules of MAb size (150 KD) and of small molecules (less than 1KD) in solid tissues gave rise to a new therapeutical concept called two phase immunotherapy. This concept is based on the separation of the localisation phase, the phase in which the MAb + X molecule localises at the position where therapy is desired, from the toxic phase. During the toxic phase, a untoxic "substance" develops a toxic activity by the action of the MAb + X only at the desired localisation. This concept is presently converted into practice in numerous different approaches, for example in a two phase tumor radioimmunotherapy, in a immune specific enzyme mediated chemotherapy (ISEC) and in a concept using Major Histocompatibility (MHC) antigen specific CTL as toxic agents to destroy MHC class I labeled target cells. PMID- 2096820 TI - Properties of FV and Fab fragments of the antibody McPC603 expressed in E. coli. AB - The FV and Fab fragments of the phosphorylcholine binding antibody McPC603 were functionally expressed in E. coli. This was achieved by the co-expression and co secretion of both chains to the periplasm, where correct processing, folding and assembly occurred. Interestingly, the fraction of correctly folded Fab fragment is smaller than that of the Fv fragment in E. coli. The intrinsic hapten binding affinity was shown to be identical for the recombinant FV or Fab fragment, the whole antibody and the Fab fragment obtained by proteolysis from the mouse antibody. Fluorescence and crosslinking analyses showed that the FV fragment dissociates at high dilution, but that it is stabilized by hapten binding. The recombinant FV fragment was shown to have catalytic activity to hydrolyze choline p-nitrophenyl carbonate and constitutes therefore a promising model system with which the structural requirements of catalytic antibodies can be studied by altering the protein itself. PMID- 2096821 TI - Percolation and binding of MAB BW 494 to pancreatic carcinoma tissues during high dose immunotherapy and consequences for future therapy modalities. AB - The distribution of the monoclonal antibody (MAb) BW494 in human pancreatic carcinoma biopsies during high dose i.v. immunotherapy was investigated. Using immunohistochemical techniques combined with anti-idiotypic, endothelial cell specific and bispecific MAbs it was shown that 3 days after onset of immunotherapy, MAb BW494 was bivalently bound to tumor cells in some highly vascualized areas near capillaries. No binding was observed in other highly vascularized tumor cell areas although the epitope detected by MAb BW494 was present. In contrast to our expectation the majority of the tumor cells was not yet saturated by the antibody, probably due to diffusion barriers in the solid tumor tissue. PMID- 2096822 TI - Biosynthesis and assembly of MHC antigens. PMID- 2096823 TI - [Synthesis and antitumor activity of new analogs of anthracycline antibiotics modified by aglycon]. AB - Anthracycline antibiotics widely used, along with their semisynthetic analogues, in human cancer chemotherapy, are O-glycosides having as aglycon 7,8,9,10 tetrahydronaphtacenequinone-5,10-with some hydroxy groups, a side chain at C-9 and sugar(s) residues, usually at C-7. The review includes the most important studies on the chemical modification of the aglycon moiety of daunorubicin, doxorubicin and carminomycin during last ten years. Activity of the compounds on experimental tumours is described and their structure-activity relationship is discussed. PMID- 2096824 TI - [Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid]. AB - A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested. PMID- 2096825 TI - [Formation of models of the interaction between organophosphate compound structure and their ability to inhibit cholinesterase]. AB - On the basis of a discrete-regression model earlier proposed by the authors, computer modelling of relationships between structure of organophosphorous compounds and their anticholinesterase activity was carried out. Values of kinetic constants of reversible and irreversible inhibition of human erythrocyte acetylcholinesterase and horse serum butyrylcholinesterase by more than 240 phosphoryl and thiophosphoryl compounds (from own and literature data) were used as initial basis. For description of these compounds' structure informational topological, physico-chemical and donor-acceptor descriptors were used. By means of procedures of discriminant, regression and cluster analysis, the compounds studied were divided into groups according to the structure, and quantitative structure--activity correlations were found in most of the clusters. This study revealed some functional peculiarities of these compounds and allowed for rationalisation of search of effective compounds with anticholinesterase activity. PMID- 2096826 TI - [Reactivity of oligonucleotide derivatives, containing methylphosphonate groups. VI. Increase in the effectiveness of directed action of alkylating derivatives of oligonucleotide methylphosphonate analogs on nucleic acids in the presence of effectors--3',5'-bis-N-(2-hydroxyethyl)-phenazine derivatives of oligonucleotides]. AB - Effectors for increasing the efficiency of DNA modification with the alkylating methylphosphonate analogues of oligodeoxyribonucleotides (MFAO) were suggested. Oligodeoxyribonucleotide d(pC5A8ACAATG) used as a target DNA treated with alkylating derivatives of octathymidylate having alternating methylphosphonate and phosphodiester internucleotide bonds (both Rp- and Sp-individual diastereoisomers of MFAO were used) and bearing alkylating 4-(N-methyl-N-2 chloroethylamino)benzyl phosphoramide residue at the 3'-end. The reactions were carried out in the presence of an effector, hexadeoxyribonucleotide derivative PhnNH(CH2)2NHpCATTGTpNH(CH2)2NHPhn bearing two N-(2-hydroxyethyl)phenazinium (Phn) residues at the 3'- and 5'-ends and being complementary to the part of the target DNA neighbouring with octaadenylate. It was shown that Tm of the duplex formed by the target DNA, octathymidylate and effector is by 7-13 degrees C higher than in the absence of the effector, thus considerably increasing the efficiency of the intracomplex alkylation of the target (e.g., at 40 degrees C, the increase for the reagent based on the Rp-isomer is sixfold). Specificity of the target DNA modification by the MFAO alkylating derivatives in the presence of effector is same as with reagents based on oligodeoxyribonucleotides with natural internucleotide bonds. PMID- 2096827 TI - [Synthesis of oligoribonucleotides by the N-phosphonate method using alkali labile 2'-o-protective groups. II. Various aspects of using 2'-o-benzoyl and anisole protective groups]. AB - The N-acyl, 5'-O-trityl (MeOTr, (MeO)2Tr, Me3Tr), 2'-O-benzoyl (and anisole) nucleosides were prepared by selective aroylation of N,5'-protected nucleosides. By means of the reverse-phase microcolumn liquid chromatography it was shown that the rate of the aryl 2'----3'-isomerisation is lower in case of 2' anisoylnucleosides and depends on structure of the 5'-O-protecting group. The prepared synthons were used for the manual H-phosphonate solid-phase synthesis of oligoribonucleotides (6-10-mers). PMID- 2096828 TI - [A crustacean-specific neurotoxin from the venom of the black widow spider Latrodectus mactans tredecimguttatus]. AB - A method of the isolation of a crustacea-specific neurotoxin from the venom of the Latrodectus mactans tredecimguttatus spider by means of ion exchange chromatography on Mono Q and Mono S columns and hydrophobic chromatography on Phenyl-Superose column has been developed. LD50 of the toxin has been elucidated. PMID- 2096829 TI - [Synthesis of the mature human interleukin-1(alpha) gene by amplification of an mRNA-cDNA duplex in vitro]. AB - Mixture of polyadenylated mRNAs from human monocytes has been subjected to the reverse transcription specifically initiated from the mRNA encoding interleukin 1 alpha by a synthetic polynucleotide complementary to the mRNA's coding 3'-end to yield the corresponding mRNA-cDNA duplex. Under conditions of the polymerase chain reaction, with the above polynucleotide as a downstream primer and an upstream primer corresponding to the beginning of the mature interleukin 1 alpha (AA 113-271) gene, the mRNA-cDNA duplex yielded the desired gene, whose structure was proved by the restriction and sequence analyses. The gene, containing translation initiation and termination triplets, can be used for producing interleukin 1 alpha in various expression systems and as a probe in studies of the lymphokine's biosynthesis. This method of the gene synthesis does not need construction and analysis of cDNA libraries nor synthesis of double-stranded DNA, and can, in principle, make use of the total (non-fractionated) cellular RNA. PMID- 2096830 TI - The validity of animal models in the search for drugs for the aging brain. AB - The search for drugs of use in the treatment of age-associated memory impairment, multi-infarct dementia, and Alzheimer's disease is frustrated by the expense or inadequacy of animal models of these conditions. We hope that this critical review of existing models will stimulate the use and proper interpretation of the best of these models, and encourage thinking in devising new models. PMID- 2096832 TI - Brain and CSF specific chemical delivery systems for beta-lactam antibiotics. Study of two dihydropyridine derivatives of benzylpenicillin in rabbits and dogs. AB - Following previous studies in rats, the ability of two chemical delivery systems (CDSs) to deliver benzyl penicillin (1) to the central nervous system of rabbits and dogs was investigated. One of the systems (3) was a diester of methylene diol, and the other (5) a diester of ethylene 1,2-diol; in both, one hydroxyl group of the diol was esterified by the 3-carboxylic acid group of benzylpenicillin, and the other by the carboxy group of an N methyldihydropyridine (dihydrotrigonelline). The basis of the system is the ability of the dihydropyridine components to undergo oxidation to quaternary pyridinium salts (2 from 3, and 4 from 5). In vitro relative stability studies were first performed in 10% rabbit brain homogenate, rabbit CSF and dog CSF. The results showed that the CDSs (3 and 5) were more stable than the corresponding quaternary salts (2 and 4). Hydrolysis of 2 and 3 resulted in the release of 1, whereas hydrolysis of 4 and 5 released both 1 and the hydroxyethyl ester (6) of 1. In vivo distribution studies were performed in rabbits and dogs. After i.v. administration of equimolar doses of 1 or the CDSs, levels of 1 in brain and CSF were substantially higher and more prolonged in the cases of the CDSs than in the case of 1 itself. Brain levels of 1 were lower following administration of 5, as compared with 3, due to the release of the intermediate compound, the hydroxyethyl ester (6) of 1, which was not hydrolyzed efficiently to 1 in rabbit or dog brain. The substantially increased and prolonged penicillin levels following administration of the CDSs arise as the result of improved penetration of the lipophilic CDSs across the blood-brain barrier, and a "lock-in" effect of the corresponding quaternary salts generated in situ. PMID- 2096831 TI - Synthesis and calcium channel antagonist activity of nifedipine analogues containing 4-pyridyl and 3-arylethyloxycarbonyl substituents. AB - A series of unsymmetrical 3-arylethyl 5-isopropyl ester analogues of nifedipine, in which the 2'-nitrophenyl group at the 4 position is replaced by 2'- or 3' pyridyl, were prepared and evaluated as calcium channel antagonists. The point of attachment of the pyridyl substituent was a determinant of activity, 2'-pyridyl analogues always being more potent than corresponding 3'-pyridyl analogues. The introduction of a substituent at the para-position of the phenethyl group in 3 phenethyl ester analogues usually enhanced the activity. The most potent compound was 3-(4'-bromophenethyl) 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-(2'-pyridyl)-3,5 pyridinedicarboxylate. It was 82-fold more potent than nifedipine, and it did not exhibit a negative inotropic effect on guinea pig left atrium. Desirable features in 1,4-dihydropyridine calcium antagonists of the unsymmetrical 3,5-diester type are therefore a 4-(2-pyridyl) substituent in conjunction with a hydrophobic 3-(4 substituted-phenethyl) ester substituent. The arylethyl ester and the 4-(2' pyridyl) substituents appear to provide important interdependent contributions to the calcium channel antagonist activity. PMID- 2096833 TI - Charge densities of atoms of conjugated styryl ketones having activity against L1210 leukemia cells. AB - Electron density calculations were undertaken on several atoms in a series of 3 substituted-4-phenyl-3-buten-2-ones in order to gain insight into the molecular features which affect charge densities. The results indicate that substituents at position 3 alter the electron densities of the olefinic group but have little effect on the acetyl function. The compounds were tested against L1210 cells in vitro, and the results suggest that electronic--but not steric--factors are important in affecting cytotoxicity. The most active compound was 3 phenylmethylene-2,4-pentanedione (1c) with an ED50 value of 1.06 x 10(-8) M. PMID- 2096834 TI - Cytotoxicity of Mannich bases of alpha-arylidene-beta-ketoesters and related compounds against EMT6 mammary carcinoma cells. AB - A number of Mannich bases 2 derived from alpha-arylidene-beta-ketoesters, some corresponding deaminated products 3, and a thiol adduct 5 were prepared. High resolution 1H NMR spectroscopy revealed that, in solution, most of the bases 2 existed principally in acyclic forms, but that all members of this series underwent some intramolecular cyclization. The compounds 2, 3 and 5 possessed activity against EMT6 mammary carcinoma cells. The Mannich bases 2a-e had the highest cytotoxicity. Topliss analysis of these compounds revealed an E4 parameter dependency, in which intramolecular cyclization was minimal. The Mannich base 2f--which existed principally in the cyclic forms 6 in deuterium oxide, the deamination products, and a thiol adduct had approximately one-sixth of the activity of 2a-e. PMID- 2096835 TI - Inhibitory effect of beta-cyclodextrin on ampicillin polymerization in aqueous solution. AB - Ampicillin polymerizes in aqueous solution to produce antigenic polymers; the polymers were separated by anion-exchange chromatography and shown to consist of a dimer, trimer, tetramer and pentamer of ampicillin by the masses found in fast atom bombardment mass spectroscopy. The presence of an intact beta-lactam ring in each of the polymers was revealed by the characteristic positive Cotton effect near 230 nm in their circular dichroism spectra. beta-Cyclodextrin was found to inhibit this polymerization by complex formation involving equimolar quantities of the constituents. Formation of this complex was complete in 10% aqueous solution within 6 hr at 24 degrees C. The positive Cotton effect arising from the beta-lactam ring decreased as the degree of polymerization increased, but was unchanged by the complex formation with beta-cyclodextrin. PMID- 2096836 TI - [Dynamics of changes of anteroposterior jaw positions relative to the cranial base during the second trimester of normal intrauterine growth]. AB - The aim of this investigation was to estimate dynamics of changes of maxillary (SNAns) and mandibular (SNMe) prognathism relative of the cranial base from 14th to 24th week of normal intrauterine growth. Investigation was performed on lateral cephalometric radiographs of 50 fetuses, both sexes, derived from artificial abortions in advanced uncomplicated pregnancies, due to social indication. Estimation of gestational ages was made according to contemporary ultrasonic standards of the normal fetal growth. The results obtained from this study showed that enlargement of the SNAns angle was relatively more rapid and regular (2.806 degrees +/- 0.483 degrees per week). The average change of this angle was from 61.047 degrees (in 14th week) to 89.107 degrees (in 24th week), with total change of 28.060 degrees during the period investigated. On the other hand, enlargement of the SNMe angle was, relatively, moderate an variably of 1.678 degrees +/- 0.597 degrees per week. Changes of this angle were ranged, in average from 46.295 degrees (in 14th week) to 63.074 degrees (in 24th week), with the total change of the 16.780 degrees during the same period. Rhythm of enlargement of SNAns angle was 76.222% more rapid than in SNMe angle (p less than 0.05). However, individual variability of SNMe angle enlargement was 23.602% higher compared with SNAns angle (p greater than 0.05). The author concluded that changes of anteroposterior position of the upper jaw relative to the cranial base ranged from marked retrognathism to mild prognathism. During the period investigated, changes of anteroposterior position of the lower jaw relative to the cranial base ranged from marked to moderate retrognathism. PMID- 2096837 TI - [Craniofacial dimensions in twins]. AB - In order to estimate the role of the genetic and ecological factors in the craniofacial growth, study has been made on 36 monozygotic (MZ) and 31 dizygotic (DZ) twin pairs of the same sex. Standard anthropological instruments were used. The following dimensions were examined: the stature, Eu-Eu, G-Op, Zy-Zy, Go-Go, N Gn and N-Pr. The results are represented in 2 tables and 3 histograms. The result indicate the largest variability of N-Pr and the smallest variability of Zy-Zy within the MZ twins while within the DZ twin pairs it is revers, which suggests that the bizygomatic width is more genetically dependent than the upper height of the face. No statistically significant differences occur within the MZ pairs, except for the stature. On the other hand, within DZ pairs the differences are statistically significant (except for G-Op). The intracorrelations are greater for all the MZ variables. The heredity and cultural inheritance index show higher value of c2 for all variables, which suggests a higher influence of the environmental than that of the genetic factors (h2). A hypothesis would be that the shape of the head and the upper facial height are easily influenced than the Zy-Zy and the morphological face height. PMID- 2096838 TI - [Roentgen cephalometric analysis of linear variables in a sample with normal occlusion]. AB - Eight linear variables have been analysed in a sample of 200 persons with normal occlusion. Selected variables define the cranial base, basal planes of both jaws, anterior face height, upper and lower segment of the anterior face height, posterior face height and mandibular height. Particular aim of this investigation was to establish the differences according to age and sex, to describe the correlations as well as to define the proportional relations among the selected linear variables. From the results obtained the following conclusions were drawn: All variables increased by growing up; the greatest increase was found in posterior face height, and the smallest in cranial base length, The highest correlation was found between variables defining both facial heights. Index defining proportion between posterior and anterior face height (65.4) showed a horizontal growth tendency in the population investigated. PMID- 2096839 TI - [Cephalometric analysis of morphological characteristics of the cranial base in cases with unilateral and bilateral clefts of the lip and palate]. AB - Lateral cephalometric radiographs of 31 cases with unilateral clefts of the lip and palate, 31 cases with complete bilateral clefts of the lip and palate as well as 31 cases with skeletal class I relationship were used for this study. The following angular and linear measurements were analysed: NSBa, SBaN, BaSN, S-N, S Ba and N-Ba. The groups were compared with each other for all measurements studied. There was no significant difference between these groups for NSBa and SBaN angles. The mean value of the BaSN angle was significantly lower in the group with complete unilateral clefts of the lip and palate than in the remaining two groups. The mean values for linear measurements investigated were significantly lower in the group with unilateral clefts than in the remaining two groups. PMID- 2096840 TI - [Variations of sagittal skeletal relationships in cases with normal occlusion]. AB - Cephalometric radiographs of a sample of 92 cases with normal occlusion were used to study variations in the sagittal jaw relationship. The Schwarz's and Steiner's cephalometric methods of analysis were employed. Results obtained by the Schwarz's method showed that 58.7% of cases had Class I, 16.3% Class II and 25% Class III skeletal relationship. On the other hand, the Steiner's method demonstrated Class I skeletal relationship in 59.8% cases, Class II skeletal relationship in 8.7% of cases and Class III skeletal relationship in 31.5% of cases. Both cephalometric methods indicated Class I skeletal relationship in 39.1% of all cases investigated. In addition, both methods showed the same skeletal relationship (Class I, Class II or Class III) in 58.6% of all cases investigated. PMID- 2096841 TI - [3. L Cephalometer]. AB - Authors present an original approach to the cephalometric measuring by obtaining absolute coordinates of the cephalometric points in a coordinate system fixed on the skull. An instrument especially constructed for that purpose is shown, and also the way of using it in vivo. PMID- 2096842 TI - The physical and chemical characteristics of particles in indoor air where high fluoride coal burning takes place. AB - In China, more than 10 million people suffer from fluorosis caused by the burning of high fluoride coal. Analysis of the particulate matters of indoor air from these fluorosis areas reveals a logarithmic distribution of particle sizes. The levels of F- and SO4(2-) adsorbed or absorbed on the particles ranged from 16.27 to 46.18 micrograms/m3 and from 244.7 to 374.6 micrograms/m3, respectively. Gaseous and soluble fluorides constituted a considerable proportion of the inorganic fluorides. Nevertheless, the level of F- in air was considered to be inadequate to cause the observed severity of fluorosis. It is speculated that additional intake of F- from contaminated foods might also be a major factor contributing to the fluorosis. Additionally, some volatile elements (e.g., sulfur and its derivatives) might have some relation to fluorosis of this type. PMID- 2096843 TI - Stimulation of ammonification and nitrification in soils by the insecticides monocrotophos and quinalphos. AB - The application (up to 5 kg ha-1) of monocrotophos or quinalphos to four types of agricultural soils significantly stimulated the mineralization of peptone nitrogen and the oxidation of ammonium-nitrogen. In soils treated with 2.5 kg ha 1 of either insecticide, the rate of ammonification and nitrification was fairly rapid after 2 and 4 weeks of incubation. The enhancement of both transformations, mediated by microorganisms, was significantly more in the quinalphostreated soils. The results suggest that a balance between the effect of insecticides on insect pests and their impact on beneficial microbial activities in soil must be determined. PMID- 2096844 TI - Use of in situ structural and functional variables of phytoplankton of the river Ganga for assessment of heavy metal toxicity. AB - Toxicity of Cd and Zn on autotrophic index, pigment diversity. 14C uptake, and in situ nitrogenase activity of phytoplankton of the river Ganga has been studied for the first time in India using CEPEX enclosures. Maximum reduction in algal population was noted at 8.0 micrograms ml-1 Cd followed by 8.0 micrograms ml-1 Zn. Complete elimination of two and four species was observed respectively at 4.0 and 8.0 micrograms ml-1 Cd and Zn. The filamentous forms showed greater tolerance against Cd and Zn, whereas unicellular forms were more sensitive to test metals used. Bacillariophytes in general depicted greater sensitivity for both the metals. A concentration-dependent metal-specific increase in autotrophic index and pigment diversity of phytoplankton was noted for Cd and Zn. Inhibition of carbon and nitrogen fixation was, however, concentration dependent and metal specific. Looking at the sensitivity of 14CO2 uptake rather than other variables, we recommend the employment of this parameter for assessment of heavy metal toxicity in an aquatic ecosystem. PMID- 2096845 TI - The effect of Chinese tea on the occurrence of esophageal tumors induced by N nitrosomethylbenzylamine formed in vivo. AB - Five groups of rats (22 per group) were intubated with precursors of N nitrosomethylbenzylamine (NMBzA), i.e., methylbenzylamine (1 mmol/kg body wt) and sodium nitrite (0.5 mmol/kg body wt), and with five different varieties of Chinese tea twice a week. One positive control group was intubated with precursors of NMBzA without tea, and a negative control group was given tap water and sodium nitrite only. After 12 weeks of treatment, significantly fewer lesions and papillomas in the esophageal mucosa were found in the tea-treated group than in the positive control group. The results confirmed the anticarcinogenic effects of Chinese tea in rats by blocking the in vivo formation of NMBzA. PMID- 2096846 TI - Acute toxicity of methyl isocyanate in mammals. III. Electroencephalographic changes in rabbits. AB - Electroencephalographic (EEG) changes in rabbits following subcutaneous administration of methyl isocyanate (MIC) remained essentially similar at both 0.5 LD50 and 1.0 LD50 except for the magnitude. There was slowing of the EEG, depicting a synchronized pattern with frequent delta waves. Compressed spectral analysis revealed a spreading of power to a higher frequency. Power spectral analysis showed a reduction in all four bands in the frontal-transverse leads. This study demonstrates that MIC intoxication leads to the impairment of brain function, probably through stagnant hypoxia. PMID- 2096847 TI - The effect of selenium-fortified table salt in the prevention of Keshan disease on a population of 1.05 million. AB - The preventive effect of selenium (Se)-fortified table salt against Keshan disease (an endemic myocardiopathy) was tested on 1.05 million people with another 0.6 million people as the control. The average annual incidence of acute and subacute types of the disease significantly decreased from 25.23 to 2.7 per 100,000 in the Se-supplemented population, while the corresponding rate in the control decreased from 19.76 to 7.36 per 100,000. Furthermore, the detection rate of new cases of a latent type of Keshan disease in the Se-supplemented group (0.18%) was significantly lower than that in the control group (1.07). PMID- 2096848 TI - Decontamination of landfill leachate by soils with different textures. AB - Soils with different textures (sandy, loamy, and clay soils) were used as filters to attenuate leachate from the Gin Drinkers' Bay landfill. They were used to pack columns of different depths: 0.2, 0.6, and 1.0 m. Eight millimeters of leachate was drained into the soil columns each day for 56 days. The percolated leachates were collected weekly and their properties analyzed. It was revealed that the properties became rather stable at Day 28 and therefore only the data from Day 28 are presented. The effluents from the loamy and clay columns with depths of 0.6 and 1.0 m contained significantly lower (P less than 0.05) ammonia contents and had lower chemical oxygen demand than those from sandy soil columns. Moreover, the depth of the columns of loam and clay did not show a significant difference (P greater than 0.05). Sandy soil was the least effective in attenuating the leachate. The efficiency of all the soil columns decrease as the soil depth decreased. It was also noted that growing of tree seedings (Acacia confusa) could further improve the efficiency of the loamy soil, especially for the removal of Na. The phytotoxicity of the raw and percolated leachate was evaluated using seed germination of two plant species (Brassica chinensis and Lolium perenne) and the growth of an uncellular green alga (Chlorella pyrenoidosa). In general, the raw leachate was toxic and inhibited seed germination and root growth of the two plant species and the growth rate of the unicellular green alga. The toxicity was due to the high levels of ammonia-nitrogen. COD, iron, manganese, and sodium ions. Percolated leachate, especially from loamy and clay soil columns, exhibited a decrease in phytotoxicity. Clay or loamy soil columns of 0.6-m soil depth seemed to be sufficient to remove the phytotoxic substances in landfill leachate. PMID- 2096849 TI - Airborne endotoxin concentrations in various work areas within two cotton textile mills in the People's Republic of China. AB - As part of a multidisciplinary longitudinal approach to assess the roles of airborne cotton dust and endotoxins in affecting the respiratory health of cotton textile workers, this study was designed to quantify the endotoxin contamination of airborne vertically elutriated and total dusts. Yarn preparation areas (opening through fine spinning) were studied at two cotton textile mills which had been studied 5 years previously in Shanghai. People's Republic of China, Filter, with vertically elutriated (VE) or total dusts were mailed to the United States and endotoxin analyses were performed for each filter in duplicate with the quantitative chromogenic modification of the Limulus amebocyte lysate assay. Dusts from all areas of the textile mills contained endotoxins. Endotoxin burdens in VE dusts from the carding area were similar in both milk while the endotoxin contamination of total dust from carding in Mill 1 was over threefold greater than that of total dust from carding in Mill 2. All other areas differed between milk in both VE and total dust endotoxin burdens. Mean endotoxin levels in VE dusts from all areas of both mills were well above the reported threshold of 90 EU/m3 for acute pulmonary function effects in humans. Comparison of selected areas of both mills from the present study with the same work areas from the previous study showed that, in general, the airborne endotoxin burden was higher than levels found 5 years ago in these two mills. The data suggest that even with reduced or unchanged gravimetric dust levels in these two cotton textile mills, airborne endotoxin levels were higher and provided an increased potential for adverse respiratory response in exposed workers. PMID- 2096850 TI - Long-term toxicity studies of styrene maleic anhydride in rats. AB - In male Charles Foster rats, polymer styrene maleic anhydride was injected into the lumen of the vas deferens at dose levels of 1.0, 2.5, and 5.0 mg in each vas deferens of Groups II, III, and IV, respectively, while controls (Group I) received 0.03 ml dimethyl sulfoxide in each vas deferens. The rats were observed for 6 months for toxicity. No change in any of the toxicity parameters in test animals as compared to controls was revealed. Hence, the polymer is safe at the doses used within 6 months of injection. PMID- 2096851 TI - Evaluation of prenatal nutrition counseling: maternal nutrition status and infant birthweight. AB - A prospective study on the effect of prenatal nutrition counseling on maternal nutrition status and infant birthweight was conducted at an antenatal care clinic by comparing a group of 80 women who attended nutrition counseling sessions with another group of 63 women who did not participate in nutrition counseling (controls). The daily intake of protein, calcium, iron, retinol, and riboflavin in the counseled group was higher than that in the control group. Moreover, the daily intake of nutrients of the counseled women met the recommended dietary allowance. Blood constituent determinations revealed that the levels of serum total protein, albumin, vitamin A, vitamin E, zinc, copper, magnesium, and hemoglobin in the blood of mothers and in umbilical blood at delivery were higher in the counseled group than in the control group (P less than 0.01). The women receiving counseling had fewer low-birthweight infants (1.52% vs 2.70%) and the incidence of maternal anemia was 39.1% against 55.6%, a significant difference (P less than 0.01). PMID- 2096852 TI - Mental health services in Japan. PMID- 2096853 TI - Etiology and outcome of acute viral hepatitis in Korean adults. AB - One hundred and sixteen Korean adults with biopsy-proven acute viral hepatitis were studied to determine the etiology and the outcome of the disease using paired sera obtained during acute and convalescent phases. The prevalence of acute viral hepatitis A, B, D and non-A non-B were 3.4%, 60.3%, 0.9% and 35.3%, respectively: hepatitis B virus infection was the most common cause and the hepatitis D virus superinfection was almost negligible. Only eleven (26.8%) of 41 patients with AVH NANB were negative for all serological markers of HBV. The rest (73.2%) were positive for at least one HBV marker: HBsAg was positive in 31.7%. Therefore, the presence of HBV serologic markers in the sera does not exclude the diagnosis of AVH NANB in Korea. In patients with acute viral hepatitis B, 27% remained positive for HBsAg. Chronic hepatitis developed in 12.8% and 17% patients with acute hepatitis B and non-A non-B, respectively. Progression to chronic hepatitis in patients with acute viral hepatitis B and non-A non-B occurred more commonly, although statistically not significant, in male sex and in patients who did not have clinical jaundice during the acute phase and who showed bridging necrosis in their liver biopsies. Age did not influence the progression to chronic hepatitis. PMID- 2096854 TI - Cervical intramedullary neurofibroma. AB - Intramedullary spinal neurofibroma is extremely rare. A case of cervical intramedullary neurofibroma is presented in a 21-year-old man. Only 20 case have been previously reported in the literature. The site of origin is discussed with various hypotheses. PMID- 2096855 TI - Two cases of suspected arteriosclerotic optical chiasmal syndrome. AB - Optic chiasmal syndrome due to arteriosclerotic vascular changes is rate. To our knowledge, there has been no report of arteriosclerotic chiasmal syndrome in Korea. In our two cases, other causes of chiasmal syndrome were not detected by MRI, four-vessel cerebral angiography, CSF study, and special laboratory examinations including ANA test, RA factor, and LE cell. With conservative treatment, the visual fields of the two patients are showing progressive improvement. We report here two cases of suspected arteriosclerotic optic chiasmal syndrome. PMID- 2096856 TI - Nasal hemangiopericytoma--a case report. AB - A case of rare intranasal hemangiopericytoma in a 68-year-old male was reported with typical histological and ultrastructural findings. The lesion clinically resembled a nasal polyp. The experience in the present case raised the need for differential diagnoses of vascularised spindle cell tumors and of traditional hemangiopericytoma in soft tissue. PMID- 2096857 TI - Postoperative problems: current nursing management. PMID- 2096858 TI - Pulmonary problems. AB - Prevention of pulmonary complications continues to be a major goal of therapy in the care of patients in the postoperative period. Numerous factors, including anesthesia and surgery-induced diaphragmatic dysfunction, reductions in lung volumes and capacities, and release of mediators that damage the endothelium, set the stage for the development of complications such as atelectasis, pneumonia, and ARDS. Nursing assessment focuses on the early identification and evaluation of respiratory distress and degree of oxygen supply/demand imbalance. Intervention focuses on restoration of appropriate ventilation/perfusion matching and provision of adequate oxygen to meet tissue metabolic demands. PMID- 2096859 TI - Pain management. AB - Postoperative pain management in the critically ill patient is a challenge for nurses. Knowing the basis of pain transmission and mechanisms of action of interventions can assist the critical care nurse in making clinical decisions regarding pain control for individual patients. There are a number of modalities available to treat postoperative pain including both pharmacologic and nonpharmacologic interventions. Techniques such as PCA not only can provide good analgesia, but allow the critically ill patient at least one aspect of control in the otherwise highly controlled environment of the critical care unit. Epidural or intrathecal analgesia, using either opioids or LAAs alone or in combination, provides excellent analgesic effect (with minimal side effects) and may improve patient outcomes. Nonpharmacologic techniques, unfortunately, are commonly overlooked as adjuncts to traditional analgesia routines because of the nature of the illness in the critically ill patient. Nonpharmacologic techniques of pain management have a place in the care of the critically ill when applied based on the assessment of an individual patient's needs and abilities to participate in his or her care. Ensuring optimal patient comfort can benefit critically ill patients and improve clinical outcomes. PMID- 2096860 TI - Postoperative bleeding. Current nursing management. AB - The critical care nurse caring for the postoperative bleeding patient must have a thorough knowledge of basic hemostatic principles and inherited and acquired disorders. Early recognition and treatment of bleeding problems reduces surgical morbidity and mortality; therefore astute clinical observations and a thorough understanding of selected laboratory testing are imperative. Because of the risk of disease transmission associated with homologous blood transfusion, new alternatives in blood therapy--autologous blood from preoperative and perioperative salvage; the conservative and individualized use of homologous blood and its components; blood substitutes to support oxygen transport (e.g., modified hemoglobin solutions and perfluorochemical emulsions); new pharmacologic approaches for minimizing blood loss (e.g., desmopressin); and increasing the body's ability to produce blood (e.g., recombinant erythropoietin)--must be considered and the patient response carefully assessed. A broad knowledge base and clinical expertise are requisite in meeting the critical needs of the postoperative bleeding patient in a climate of rapidly developing diagnostic and therapeutic alternatives. PMID- 2096861 TI - Postoperative perfusion deficits. AB - The three keys to successful recovery of the critically ill postoperative patient are: (1) in-depth preoperative assessment and risk evaluation; (2) review of intraoperative course and evaluation of risk for perfusion deficit; and (3) diligent postoperative monitoring for early onset of perfusion deficit. Complications arise when metabolic demands exceed the body's ability to supply essential nutrients. The choice of treatment modality is related to the cause of perfusion deficits. Decreased preload and afterload is treated with fluid and vasopressor therapy. Increased preload is best managed by diuretics and venous dilation. Afterload reduction is accomplished with vasodilator therapy and decreases in sympathetic stimulation. Contraction is enhanced with inotropic therapy and management of preload and afterload within normal ranges. Metabolic demands are best managed with tight control of the patient's hemodynamic profile, oxygen consumption, and environmental stimuli. The challenge of managing the critically ill postoperative patient is great, but the rewards of successful recovery are tremendous. PMID- 2096862 TI - Postoperative confusion. AB - Confusion is a terrible feeling, a feeling of being lost in the most basic sense. The markers, maps, cues, and senses used to orient oneself to the immediate environment are not recognizable. This applies to what one sees, hears, and feels. The person searches for something that makes sense, that he or she can anchor thoughts or actions to. Sitting up, getting up, and walking are anchoring responses. Using hands to touch one's own body, fingering objects, and "calling out" reflect a searching for something that is meaningful to the individual. Patients in various clinical settings who have experienced confusion all report common feelings: anxiety, fear of dying or being hurt, pain, falling, floating, suffocating, feelings of being crazy, being chained, or being lost. The severely confused seem only able to share the experience through their behavior; but it is clear that acute confusion is a physiologic and psychological assault on the body and mind, often worsened by nursing and medical interventions. Acute confusion continues to be a misdiagnosed and undertreated problem. Continued clinical inquiry and research into acute confusion and the use of such knowledge in the practice setting can reverse this trend. PMID- 2096863 TI - Temperature problems in the postoperative period. AB - Postoperative patients have difficulty maintaining thermal balance for several reasons. Normal thermoregulation is suppressed by anesthesia, neuromuscular blocking agents, and other drugs, and cool environmental conditions and exposure contribute to heat loss. Specific patient groups at high risk for hypothermia include infants, the elderly, and the neurologically impaired. Temperature drift, afterfall, shivering, malignant hyperthermia, and fever are among the temperature related conditions requiring vigilant assessment and nursing action during the postoperative period. PMID- 2096865 TI - Thrombolytic therapy. PMID- 2096864 TI - Postoperative care of the critically ill child. AB - Postoperative care of the pediatric surgical patient requires knowledge of the signs of cardiorespiratory and neurologic deterioration in the child as well as familiarity with particular postoperative complications associated with various types of surgery. This article briefly reviewed the principles of postoperative care of the critically ill child, and included references for more comprehensive sources of information. PMID- 2096866 TI - Pharmacologic review of thrombolytic agents. AB - Thrombolytic therapy has significantly reduced the morbidity and mortality that was once associated with acute myocardial infarction. Because of the substantial benefits associated with this therapy, investigation has intensified in search of the optimal agent or agents. Five agents are currently being investigated individually and in various combinations to determine which agent(s) will outperform the others in terms of reperfusion, patency, mortality reduction, and clinical events. Two of the agents, t-PA and scu-PA, are considered fibrin selective, whereas the other three, streptokinase, urokinase and APSAC are nonselective. Whether this distinction provides substantial benefit is still not known. All of the FDA-approved agents (streptokinase, t-PA, and APSAC) have demonstrated survival benefit and will continue to be administered in AMI patients. In addition, the 1990s begins a new era that includes broadened selection criteria for AMI patients as well as expanding cardiovascular indications for thrombolytic therapy. The challenge to nurses is to improve and implement nursing care practices at the same rapid pace set by the medical discipline. This includes astute assessment and observational skills necessary to prevent and detect potential complications associated with thrombolytic therapy. Rapidly changing medical techniques mandate ongoing nursing research, which is needed to determine the most effective interventions in reducing complications associated with thrombolytic therapy and in promoting positive adaptive behaviors in the AMI patient. Thrombolytic therapy is an intervention for the 1990s, and nursing care is essential in maintaining the beneficial effects of this dynamic therapy. PMID- 2096867 TI - Quality-assurance monitoring in thrombolytic therapy. AB - Use of thrombolytic agents for patients within the first 6 hours of AMI has become a standard approach to care. With this standard approach the nurse is charged with the task of not only skillfully administering this therapy, but also with monitoring its safe, effective, and appropriate use. The presence of well established standards for thrombolytic therapy serve a twofold purpose: that of promoting continuity and consistency of care. The QA process evolves out of these set standards. It seeks to determine compliance to standards and to identify existing problems. One of the most effective approaches to this process is a unit based approach. This type of approach enhances clinical competence and increases professional accountability. Finally, the QA process is a systematic means by which identified problems are addressed and reevaluated. In so doing, quality in the use of thrombolytic therapy may be maintained. PMID- 2096868 TI - Methods to limit reinfarction and ischemia after thrombolytic therapy. AB - Thrombolytic therapy has greatly influenced the long-term outcome of thousands of patients suffering AMI. The incidence of reocclusion and recurrent ischemia are continuing problems that need to be confronted if thrombolytic therapy is to have its full impact on the care of these patients. Clinical studies are providing more information on the best adjunctive therapy to accompany thrombolysis. Nursing has the potential to improve the outcome of patients by assuring the methods of preventing reocclusion we have available are skillfully implemented. If reocclusion occurs, nurses can identify the event and initiate treatment before substantial myocardium is lost. In the future, noninvasive methods to identify which patients will reocclude may be available. Thrombolytic "cocktails" or medications such as antiplatelet antibodies may be useful and may abolish reocclusion completely. PMID- 2096869 TI - Thrombolytic therapy and the nursing profession. Results of a statewide survey. AB - A statewide survey of 624 nurses in 92 hospitals in Massachusetts indicates that recombinant tissue-type plasminogen activator and streptokinase are the most widely available thrombolytic agents. Nurses play an active role in drug reconstitution and administration, but only 20% of the total respondents participate consistently in screening procedures. The majority of patients were informed about the risks and benefits of treatment before initiation of therapy. Nurses reported their major management concern was internal bleeding, with cost of treatment being a minor concern. PMID- 2096870 TI - Myocardial reperfusion injury. AB - A review of the mechanism of ischemic-reperfusion injury, proposed interventions to prevent injury, and future directions have been presented to enhance the practitioner's knowledge of this new, exciting concept in myocardial injury. There is increasing evidence in the literature that reperfusion injury may occur in other organ systems and is responsible for some of the more prevalent pathologies seen in critically ill patients. Investigators have indicated that the tissue damage in sepsis, the development of adult respiratory distress syndrome (ARDS), delayed organ recovery in transplanted organs, and delayed ventricular recovery after cardiopulmonary bypass may be attributed to reperfusion injury. The next few years will prove to be exciting as this concept is further investigated and refined. Critical care nurses need to understand the concept of reperfusion injury and may soon begin to apply the results of ongoing research studies to patients undergoing reperfusion. PMID- 2096871 TI - Findings on the efficacy and safety of thrombolytic therapy. An analysis of key clinical trials. AB - This past decade has seen remarkable progress in the use of thrombolytic agents to increase survival after AMI. Early IC strategies and several reperfusion trials of thrombolytic therapy visually demonstrated the efficacy of these agents. The life-saving benefits of thrombolysis have been illustrated by the large multicenter mortality trials with decreases in mortality from 15% to 8%. Mortality rates in AMI treated with rt-PA has been shown to be much lower in studies using full-dose IV heparin: TIMI IIB 4.9% (6 weeks), ASSET 7.2% (1 month), ECSG 3.7% (21 days). SK and APSAC are most effective at achieving thrombolysis when administered early in the course of AMI; rt-PA retains its superior efficacy on the older thrombus. When patients are properly screened for contraindications, IV-thrombolytic therapy is a safe and highly effective treatment for AMI. The choice of agent remains that of personal or institutional preference. Only when definitive results of ongoing and future head-to-head clinical trials are published can the effectiveness of the agents be compared accurately. Until these data are available, the most important lesson is to treat and treat quickly. PMID- 2096872 TI - Peripheral arterial thrombolytic therapy. AB - The management of the patient with an acute arterial occlusion or pulmonary embolus presents many challenges. Thrombolytic therapy offers a treatment option that was not available in the past. We now have several nonsurgical options for treating patients with both peripheral arterial and pulmonary arterial occlusions. There are choices as to the appropriate drug as well as the route, dose, and length of administration. The work underway is aimed at refining technique. Studies that are ongoing now focus on which drug and mode of delivery benefits certain groups of patients. Although each clinical situation is unique, the guidelines to be established through further investigations will aid clinicians in selecting the appropriate therapeutic modality. PMID- 2096873 TI - Early recognition and treatment of the patient suffering from acute myocardial infarction. A description of the Myocardial Infarction Triage and Intervention Project. AB - Involving emergency medical personnel in the evaluation and treatment of the AMI patients is feasible. A standard, organized approach saves time. Obtaining an ECG in the prehospital setting is also feasible and decreases the delay to diagnosis and subsequent treatment for patients after hospital arrival. Early findings from the MITI registry suggests that only 20% to 30% of patients with AMI are currently eligible to receive thrombolytic medications. This seems to indicate that either current treatment guidelines need to be broadened or that thrombolytic therapy is not appropriate for all AMI patients and, therefore, alternative acute treatment approaches need to be investigated further. PMID- 2096874 TI - [Inhibition and efferent facilitation of sensory activity in the isolated labyrinth of the frog]. AB - The functioning modalities of the efferent system were analysed in the isolated frog labyrinth. The efferent synapses of the posterior canal were activated via an axon reflex by antidromic electrical shocks (10-200 Hz) applied for increasing times (250 ms-10 s) to the anterior-horizontal nerves. Either decrease (inhibition) or increase (facilitation) in the resting discharge rate were observed in the majority of the units examined. Inhibition and facilitation, however, are peculiar to any given unit since inhibition does not reverse to facilitation or vice-versa. This fact as well as the long response latency (not less than 10 ms) and the linear dependence of both effects on the stimulation frequency suggest that inhibition and facilitation are due to the repetitive activation of two different types of efferent fibres synapsing on the hair cells. The drastic modifications in the afferent synaptic discharge produced by full activation of the efferent system indicate that the static properties (response asymmetry) as well as the dynamic properties (response adaptation) of the mechanically driven afferent response can be substantially controlled by the central nervous system at the receptor level. PMID- 2096876 TI - Diet restriction decreases the membrane microviscosity of cerebellar membranes of old female Wistar rats. AB - The microviscosity of cerebellar membranes from female Wistar rats during aging and subsequent to diet restriction has been investigated. Diet restriction was applied feeding the animals on every-other-day schedule starting from the age of 3.5 months. Undernutrition increased the lifespan of the animals and retarded the appearance of the age-dependent increase of microviscosity of cerebellar membranes. PMID- 2096875 TI - Antioxidant enzymes in erythrocytes from old and diet restricted old rats. AB - Diet restriction, prolonging the lifespan of rodents, represents an interesting model for gerontological studies. We analyzed the activity of antioxidant enzymes, Superoxide Dismutase, Catalase and Glutathione Peroxidase in erythrocytes from young, old and old food restricted Wistar rats. Diet restriction was applied feeding the animals on every-other-day schedule starting from the age of 3.5 months. The age-dependent decrease of Catalase and Glutathione Peroxidase activities was prevented by food restriction, whereas Superoxide Dismutase activity was not influenced either by aging and dietary intervention. Present results support the hypothesis that diet restriction increases the protection of cell structure against the peroxidative damage, preserving the activity of antioxidant enzymes. PMID- 2096877 TI - [Serum levels of Cd, Pb, Cu and Zn in cigarette smokers]. AB - In order to show the accumulation of Cd, Pb, Cu and Zn in smokers, levels of these metals in serum were determined in 108 subjects: 32 non-smokers, 37 average cigarette smokers and 39 heavy cigarette smokers. The analysis was carried out by potentiometric stripping analysis (PSA) with the Tecator "Striptec System". Backward oxidation time of the amalgamated metals, by means of electrolysis, in a thin "film" of mercury in an electrode, gives their concentration measure. Our data showed an increase in average values of Cd and Pb in the serum of heavy smokers compared with average and non-smokers. Instead, as regards Cu and Zn, no differences were found in the two groups of smokers compared with the non-smokers used as controls. Results obtained of the Cd and Pb levels in serum are compatible with the presence of these metals in cigarette tobacco and inhaling them could contribute to disease connected with their accumulation in the human organism. For these subjects the increase in Cd values is of particular importance as it could predispose pulmonary emphysema. PMID- 2096878 TI - [Study of the glycoconjugates in the mesonephros of the chick embryo using peroxidase-conjugated lectin]. AB - The distribution of the sugar residues in glycoconjugates along the mesonephric nephron of chick embryo from the 4th day of incubation till hatching has been investigated, by means of six different horseradish peroxidase-labelled lectins. ConA and WGA showed an ubiquitous presence of alpha-D-mannose and N-acetyl-D glucosamine along the nephrons. SBA was found to be a specific marker of the proximal tubule. PNA and LTA reacted only for a short time at some sites during the considered period of incubation. Sialic acid was detected at the glomerulus in the podocytes, capillary wall and, with a lesser extent, in the mesangial cells. Significant changes of the glycosylation pattern of the glycoconjugates during the period of mesonephric activity and the period of involution were seen. PMID- 2096880 TI - Further researches upon the inhibiting action of lycorine on ascorbic acid biosynthesis. AB - Lycorine, an alkaloid extracted from Amarillidaceae, strongly inhibits the "in vivo" conversion of galactono-gamma-lactone to ascorbic acid. Lycorine seems to act as a non-competitive inhibitor on galactono-gamma-lactone oxidase, because the alkaloid rapidly forms a stable bound with the enzyme. In fact, a short incubation period with 50 microM lycorine gets a high inhibitory effect that persists when the alkaloid is removed from the incubation medium. Considering that lycorine induces scurvy-like symptoms in ascorbic acid-synthesising animals, it is reasonable to suppose that in both plants and animals lycorine inhibits the last step in the biosynthetic pathway leading from sugar to ascorbate. PMID- 2096879 TI - [Effect of dimethyladipimidate and dimethylsuberimidate on cell-cell adhesion in rat fibroblasts]. AB - In a study performed to identify the molecular mechanisms which regulate cell to cell adhesion and contact inhibition in neoplastic and syngeneic normal cells of the rat we have observed that the adhesive capacity depends on the reagents used, either EDTA or trypsin, to release the cells from monolayer. Taking profit of this last property and of the possibility of blocking free -NH2 groups on membrane proteins with specific cross-linking reagents "in vitro", we have studied in this work the behaviour of the proteins of the cell coat involved in cell to cell adhesion of rat fibroblasts FG/2. The cross-linking reagents used were dimethyladipimidate (DMA) and dimethylsuberimidate (DMS). The cells were exposed to the reagents at 0 degrees C for 30'. Cell to cell adhesion was measured by determining the percentage of single cells labeled with 3H-leucine, adhering to a confluent monolayer at different incubation times. The inhibitory effect on cell to cell adhesion brought about by cross-linking reagents indicates that a) EDTA-released cells are more sensitive to both imides than those released with trypsin, b) DMA is more effective on trypsin-released cells and c) DMS is more effective on EDTA-released cells. Therefore, we conclude that the inhibition of adhesion by reaction with the two cross-linking reagents is more likely due to a stiffening of the molecules of the cell coat involved in the adhesion, rather than to the modification of -NH2 residues which should specifically participate to adhesive process. PMID- 2096881 TI - [Evaluation of various hemorheological parameters in nonagenarians: evidence of an increase of fibrinogen]. AB - Cardiovascular disease is the most frequent cause of mortality in the elderly. A reduced microvascular blood flow associated with an increase in atherosclerosis might contribute to age related increases in the incidence of ischemic vascular disease. In order to evaluate the effect of age on some haemorheological parameters, blood and plasma viscosity and fibrinogen have been measured in 10 healthy elderly subjects, aged between 88 and 96 years, compared with 15 healthy young subjects (mean age 37 years). Elderly subjects showed a significant increase in plasma fibrinogen (p less than 0.0005) and a trend to an increase in plasma viscosity, whereas no difference was present in blood viscosity. These data confirm that aging is associated with a greater deal of thrombotic risk factors, the most important of which seems to be fibrinogen. PMID- 2096882 TI - [Histochemical demonstration of CEA in pathology of the colorectum]. AB - The evaluation of CEA serum levels and CEA tissue staining is one of the most common parameters used to help in the diagnosis and prognosis of colon-rectum disease. To this aim, an immunohistochemical demonstration of the CEA was carried out with the ABC staining system in sections of normal and diseased colon. 24 patients with polyps of the large intestine, 17 with rectocolitis, 22 with colon rectum cancer and 11 normal subjects were studied. Results were positive in 9, 1% of the normal mucosa, 37, 5% of the polyps, 41, 2% of the rectocolitis and 100% of the carcinomas. However, the CEA in the positive reactions showed different degrees of staining and different cellular localization. From our results it would appear that the intracellular localization of this marker is connected with the degree of atypia in the histological sections. Immunohistochemical localization of the CEA could therefore be useful, above all in assessing the prognosis of colon-rectum disease. PMID- 2096883 TI - [Insulin resistance in the uremic patient: effects of hemodialysis]. AB - The carbohydrate metabolism abnormalities present in uremia have been attributed to a combination of peripheral resistance to insulin and inhibition of insulin release secondary to beta cells insensitivity. Previous studies evaluated the chronic effects of hemodialysis on glucose metabolism, while acute effects were not examined. In 12 uremic subjects undergoing hemodialysis (3 times a week) the fasting serum levels of glucose, insulin and C-peptide were measured, and the glucose/insulin ratio was calculated as an index of peripheral sensitivity to insulin before and after dialysis. While glucose did not change, insulin and C Peptide rose significantly after dialysis. The rise in insulin and C-Peptide was directly correlated with the fall in body weight due to the fluid loss. This might indicate that the increase in insulin and C-peptide was due to a concentration phenomenon. However, it could reflect a reaction to hypoglycemia. The glucose/insulin ratio exhibited trend towards a fall after hemodialysis. Although not significant, this might indicate an acute worsening of the peripheral sensitivity to insulin, induced by the procedure. PMID- 2096884 TI - Enzymatic semisynthesis of human insulin: an update. AB - Peptide bond formation can be enzymatically catalysed by the reverse reaction of proteases. Application is seen in the industrial production of human insulin. Human insulin derivative can be enzymatically prepared using either porcine insulin or the single chain B(1-29)-A(1-21) insulin precursor as the starting material. This is accomplished by either (1) digesting the starting material at Lys29 with Achromobacter lyticus protease I (Ach) and then coupling with Thr-X (X = blocking residue) (two-step reaction) or (2) subjecting Ala-B30 of porcine insulin or Gly-A1 of the single chain insulin precursor to transpeptidation with Thr-X (one-step reaction). Trypsin and Ach can be used for either type of reaction and, in the immobilized form, for the two-step reaction. Since the single chain insulin precursor can be produced by gene technology (yeast), use of immobilized trypsin or Ach and the two-step reaction using the single chain insulin precursor as the starting material ensures the continuous production of human insulin making it a feasible method for industrial manufacture. PMID- 2096885 TI - Purification and characterization of Fab fragments from anti-mouse NGF polyclonal antibodies. AB - A functional role for Nerve Growth Factor (NGF) in the peripheral nervous system is well-documented, but a similar case for NGF in the central nervous system remains to be established. One approach to answering this question would be the availability of high-affinity monospecific Fab fragments obtained against NGF. In the present studies we describe the preparation and characterization of such Fab fragments from anti-mouse NGF polyclonal antibodies. Following their purification by the use of a NGF Sepharose-coupled affinity column, the Fab fragments were examined for biological competence in several ways. In vitro, the anti-Fab fragments blocked the neuronotrophic activity of NGF, as measured by the survival of chicken embryonic day 8 dorsal root ganglion neurons. In vivo, these Fab fragments, when administered systemically to neonatal rats, produced a decrease of noradrenaline levels in two sympathetically innervated organs, the heart and the spleen. These findings suggest that affinity purified Fab fragments of anti NGF antibodies can be a useful tool for studying the physiological function of NGF in the nervous system. PMID- 2096886 TI - Binding of the soybean Bowman-Birk proteinase inhibitor and of its chymotrypsin and trypsin inhibiting fragments to bovine alpha-chymotrypsin and bovine beta trypsin. A thermodynamic study. AB - The effect of pH and temperature on the apparent association equilibrium constant (Ka) for the binding of the soybean Bowman-Birk proteinase inhibitor (BBI) and of its chymotrypsin and trypsin inhibiting fragments (F-C(p), F-T(p) and F-T(t), respectively) to bovine alpha-chymotrypsin (alpha-chymotrypsin) and bovine beta trypsin (beta-trypsin) has been investigated. On the basis of Ka values, the proteinase inhibitor affinity can be arranged as follows: alpha-chymotrypsin: BBI approximately beta-trypsin:BBI approximately beta-trypsin:F-T(t) approximately beta-trypsin:F-T(p) much greater than alpha-chymotrypsin:F-C(p). F-C(p), F-T(p) and F-T(t) do not inhibit beta-trypsin and alpha-chymotrypsin action, respectively. On lowering the pH from 9.5 to 4.5, values of Ka for BBI, F-C(p), F T(p) and/or F-T(t) binding to alpha-chymotrypsin and beta-trypsin decrease, thus reflecting the acid-pK shift of the invariant His57 catalytic residue from 7.0, in the free enzymes, to 5.2, in the proteinase:inhibitor complexes. Considering the known molecular models, the observed binding behaviour of BBI, F-C(p), F-T(p) and F-T(t) was related to the inferred stereochemistry of the proteinase:inhibitor contact regions. PMID- 2096887 TI - Specific isolation by anhydrotrypsin-agarose chromatography of a recombinant protein tagged with an affinity tail arginine at the C-terminus. AB - A characteristic property of anhydrotrypsin, i.e., its ability to strongly bind C terminal arginine, proved to be useful as a tool for specific enrichment of a recombinant protein. An arginine tail was introduced at the C-terminus, for example, of a human beta-galactoside-binding lectin by site-directed mutagenesis. The resulting mutant recombinant lectin, which retained sugar-binding activity as high as the wild-type lectin, became recognizable by anhydrotrypsin. It was adsorbed on an anhydrotrypsin-agarose column and eluted with benzoylglycylarginine. The added arginine tail could be specifically removed by carboxypeptidase B. When E. coli lyzate containing the mutant lectin was applied to the column more than 10-fold enrichment of the mutant lectin was attained. This procedure should be generally applicable and may be advantageous because the addition of a single arginine residue may have minimal effect on the structure and function of the target protein. PMID- 2096888 TI - Citrate synthase 1 interacts with the citrate transporter of yeast mitochondria. AB - We have previously shown that citrate synthase binds to an intrinsic protein of the mitochondrial inner membrane (D'Souza and Srere, 1983). In this paper we present evidence that this citrate synthase binding protein is the citrate transporter. We have used citrate synthase 1 mutants of Saccharomyces cerevisiae and transformants containing citrate synthase inactivated by site-directed mutagenesis to study the effect of the CS1 protein upon mitochondrial function (Kispal and Srere). In the present study citrate uptake and oxidation were measured during state 3 conditions (presence of 200 microM ADP) in the mitochondria of several strains of Saccharomyces cerevesiae: a parental strain containing wild-type mitochondrial citrate synthase (CS1) and strains derived from a CS1 deficient strain in which the CS1 gene was disrupted by insertion of the LEU2 gene. These strains were generated from the CS1- cells by transformation with vectors encoding site-specific mutants of CS1 possessing very low levels of enzymatic activity. One such strain in this study was subsequently found to have undergone reversion to produce a strain which had activity very similar to wild type. Positive correlation between citrate uptake and the rate of citrate oxidation was found, suggesting coupling of the two processes. Both mitochondrial citrate uptake and oxidation were decreased in the mutant lacking any form of CS1 protein. Reintroduction of mutagenized CS1 into yeast causes an enhancement in the rate of state 3 oxygen consumption and of citrate uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096889 TI - Characterization of specific interactions of coenzymes, regulatory nucleotides and cibacron blue with nucleotide binding domains of enzymes by analytical affinity chromatography. AB - The dissociation constant for the complex of rhodanese and Cibacron Blue, determined by analytical affinity chromatography using rhodanese immobilized on controlled-pore glass (CPG) beads (200 nm pore diameter) and aminohexyl-Cibacron Blue, was 44 microM which agreed well with the kinetic inhibition constant, suggesting that the dye binds at or near the active site of this enzyme. Formation of a binary complex of the dye and lactate dehydrogenase (LDH) was also characterized by direct chromatography of LDH on CPG/immobilized Cibacron Blue (KD = 0.29 microM). The binary complex formed between LDH and NADH was characterized by analytical affinity chromatography using both CPG/immobilized LDH and immobilized Cibacron Blue. Since the dye competes with NADH in binding to the active site of LDH, competitive elution chromatography using the immobilized dye allows determination of the dissociation constant of the soluble LDH.NADH complex. Agreement between the dissociation constants determined by direct chromatography of NADH on immobilized LDH (KD = 1.4 microM) and that determined for the soluble complex (KD = 2.4 microM) indicates that immobilization of LDH did not affect the interaction. Formation of various binary, ternary and quaternary complexes of bovine liver glutamate dehydrogenase (GDH) with glutamate, NADPH, NADH, and ADP was also investigated using immobilized GDH. This approach allows characterization of the enzyme/ligand interactions without the complicating effect of enzyme self-association. The affinity for NADPH is considerably greater in the ternary complex (including glutamate) as compared to the binary complex (0.38 microM vs 22 microM); however, occupancy of the regulatory site by ADP greatly reduces the affinity in both complexes (6.4 microM and 43 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096890 TI - Efficiency of glass ionomer cement linings in preventing microleakage under Class V composite resin restorations. AB - The ability of glass ionomer linings to aid in the prevention of microleakage under Class V composite resin restorations has been investigated. A conventional glass ionomer lining (Ketac-bond) and two light cured linings (Vitrabond and Timeline) were evaluated with respect to their ability to reduce microleakage. Seventy two Class V cavities were restored either by a bulk fill or incremental fill technique, and following restoration, half the teeth were thermocycled in artificial saliva. Dye penetration, using a Procion orange dye was recorded along the gingival dentine wall and at the occlusal enamel margin for all teeth. The results showed significant differences in leakage along the gingival dentine wall between the various linings under all conditions. Vitrabond produced significantly less leakage than Ketac bond which in turn produced significantly less leakage than Timeline. Significant differences in microleakage were noted between the thermocycled and non-thermocycled groups. Little or no significant differences in leakage were shown between the bulk filled and incremental filled teeth. PMID- 2096891 TI - Significance of variable parameters in magnetic resonance imaging of the temporomandibular joint. AB - Twelve asymptomatic volunteers were examined using three different groups of Magnetic Resonance Imaging (MRI) acquisition parameters (Group a: TE 30 ms, TR 480 ms; Group B: TE 20 ms, TR 315 ms; Group C: TE 30 ms, TR 1200 ms). Altering the parameters was aimed at improving the signal to noise (S:N) ratio. Group C parameters demonstrated the best clarity of the three groups. Closed jaw views gave better images than open views in all three groups. PMID- 2096892 TI - Psychological factors in temporomandibular joint dysfunction: life events. AB - Psychological and emotional factors are clearly involved in the development of temporomandibular joint dysfunction (TMJD). They also are involved in whether the patient chooses to present for treatment and how they react to the health care professional and treatment. However, many previous studies have been simplistic in that they look at a particular psychologic aspect in isolation. In this series of studies, a multivariate analysis of a broad range of psychologic and physical variables in a TMJD group (N = 105) and a matched control group (N = 90) was performed. The methodology of the study is described in detail in this paper. Patients with high life events were compared with those with low life events. A simple relationship of high life events to development of TMJD was not demonstrated. However, high life events did correlate directly with other psychological parameters and to the development of illness behaviour. PMID- 2096893 TI - Psychological factors in temporomandibular joint dysfunction: anxiety. AB - This study was to clarify the relationship between anxiety and temporomandibular joint dysfunction (TMJD) in a group of patients with TMJD (N = 105) and a matched control group (N = 90) using measures of anxiety, relevant physical parameters and a number of other psychological variables. Patients were divided into high and low anxiety groups using the Spielberger Anxiety Inventory and compared using measures obtained from the Gerke-Goss Inventory on Dental and Psychological Factors. Statistical comparison revealed no significant differences between the anxiety groups in physical parameters. Both of the TMJD groups (high and low anxiety) revealed more prominent features of Abnormal Illness Behaviour as compared to the control groups (high and low anxiety). This prominence of Abnormal Illness Behaviour was most evident in the TMJD group with low anxiety, a finding which may have further clinical implications. PMID- 2096894 TI - Psychological factors in temporomandibular joint dysfunction: depression. AB - This study was to clarify the relationship between anxiety and temporomandibular joint dysfunction (TMJD) in a group of patients with TMJD (N = 105) and a matched control group (N = 90) using measures of depression, relevant physical parameters and a number of other psychological variables. Patients were divided into high and low depression groups using the Zung self-rating depression scale and compared using measures obtained from the Goss-Gerke Inventory on Dental and Psychological Factors. Statistical comparison revealed no significant differences between depression groups in physical parameters. The TMJD groups were generally more depressed than the control group. The highly depressed TMJD group had a greater degree of abnormal illness behaviour and generally were similar to those patients identified in other studies as being refractory to treatment. PMID- 2096895 TI - The evolution of implants over the last fifty years. AB - In discussing the evolution of implants over the last fifty years, one must consider the objectives of the use of the dental implant, the nature of its design, the biocompatibility of materials with the oral environment, research data, and finally the long-term clinical trials which have influenced the developments of such implants. PMID- 2096896 TI - Clinical study of the modified Equipoise clasp. AB - The modified Equipoise clasp has been developed to overcome the negative aesthetics of anterior clasping. Fifteen patients involving twenty-two Equipoise clasps were followed up for retention, aesthetics and oral health. Examiners found that 36.4% of the clasps gave poor retention, 18.1% were reasonable and 45.5% were good. Aesthetics were 23.6% poor, 36.4% reasonable and 50% good. Oral health was 9.1% poor, 50% reasonable and 40.9% good. The patients reported that retention was 13.3% reasonable and 86.7% good. Twenty percent of the patients felt aesthetics were reasonable and 80% felt it was good. The clasps were reasonably comfortable in 13.3% and most comfortable in 86.7%. The Equipoise clasp can be used with success for, among others, the Kennedy Class IV case if the correct clinical and laboratory procedures are followed. However, it is unsuitable in, for example, a Class I dentition where posterior stability is poor. Its lingual window can adversely affect oral hygiene and careful patient selection is necessary. PMID- 2096897 TI - System of denture assessment. AB - Denture complaints and problems can be complex in origin, time consuming to analyse, and sometimes expensive to rectify. A phased or sequential system of assessment can provide a framework on which to base the many clinical tests that may be required for the successful diagnosis of a denture problem, and will help ensure that no important factor is accidentally missed. A short mnemonic is presented which covers the assessment of the patient, the denture base and the teeth of the prosthesis. A variation of the mnemonic has been is use for several years. It is hoped that its publication might prove of value to those who, from time to time, are presented with a patient who has a denture problem. PMID- 2096898 TI - Voltammetric studies on the electrochemical behaviour of membrane-entrapped hemes. AB - The electrochemical behaviour of Fe(III)-protoporphyrin IX entrapped into a cellulose triacetate membrane has been investigated by cyclic voltammetry. The physical entrapment into a solid matrix does not modify the redox properties of the entrapped hemes, which also act as efficient promoters in the electrochemistry of cytochrome c. Such a system represents a promising example of a simple 'solid-state' promoter, and stimulates further investigations in order to obtain more complex systems that may be of significance for basic and applied bioelectrochemistry. PMID- 2096899 TI - Dynamic fluorescence in copper proteins. Selected examples. AB - The fluorescence properties of three copper proteins, namely human superoxide dismutase, Pseudomonas aeruginosa azurin and Thiobacillus versutus amicyanin have been studied. All these proteins show a non-exponential decay of fluorescence, though the tryptophanyl residues responsible for the emission are very differently located in the three proteins. All the three decays can be fitted by at least two lifetimes or better with one or two lorentzian-shaped, continuous distributions of lifetime. In each case the removal of copper affects the quantum yield of fluorescence without affecting the shape of the emission. PMID- 2096900 TI - Copper transfer through the intestinal wall. Serosal release of metallothionein. AB - The elucidation of the molecular side of copper transport in biological systems is a promising task. In this context the transfer of ingested copper into the portal blood plasma was examined. Intralumenal addition of 200 microM copper caused the release of Cu-thionein into the venous effluent. This Cu-thionein became detectable after prior perfusion of the porcine small bowel using a modified isotonic phosphate-buffered saline (Pi/NaCl) medium. The protein was characterized by gel chromatography, luminescence, electronic absorption and immunological identification. ELISA and immunoblotting employing a murine monoclonal antibody to rat liver metallothionein-I proved to be most convenient. Using buffer-loaded sacs of porcine jejunum into which Cu2+, Zn2+ and Cd2+ were added, the release of metallothionein into the serosal fluid was successfully seen by ELISA. The observed excretion of metallothionein into the portal compartment may be a genuine metal transport system for many biochemically active metals. PMID- 2096901 TI - A quarter-century biochemistry of copper with Bill Blumberg. PMID- 2096902 TI - cDNA cloning and sequencing of tarantula hemocyanin subunits. AB - Tarantula heart cDNA libraries were screened with synthetic oligonucleotide probes deduced from the highly conserved amino acid sequences of the two copper binding sites, copper A and copper B, found in chelicerate hemocyanins. Positive cDNA clones could be obtained and four different cDNA types were characterized. PMID- 2096903 TI - Analysis of patterns of twist angles in DNA double helix. AB - We have analysed theoretically the patterns of twist angles of B-DNA by the Tung Harvey model mainly. It is shown that for a sequence of twist angles a smaller twist angle tends to follow a larger one and vice versa. Therefore the sequence of twist angles always takes a gentle zig-zag form. For simplicity we convert the sequence of twist angles to a symbolic sequence consisting of L and S, where L or S represents a large or a small angle, respectively. The -10 and -35 regions of 112 well-defined promoters for E. coli RNA polymerase, which were compiled by Hawley and McClure, have been analysed in terms of LS sequences in detail. The results shows that the number of LS sequences for promoters is considerably limited and the promoter mutations do not change the patterns of LS sequences in most cases. Several new ideas, which are believed to be useful in the further study, have been presented. PMID- 2096904 TI - Creep measurements on gelatin gels. AB - The present work describes creep measurements on a series of concentrations of gelatin gels well above the critical gel concentration C0, using a high precision constant stress rheometer. Results for the concentration dependence of compliance are close to those expected both from theory and from dynamic oscillatory measurements of gel modulus. The concentration dependence of viscosity follows an approximate power law behaviour, with eta proportional C1.1. This exponent is consistent with relaxation in the sol fraction, and in regions of dangling chain attached to the gel. At concentrations closer to C0 we predict that a higher power law regime will prevail. PMID- 2096905 TI - Molecular evolution of plants as deduced from changes in free energy of 5S ribosomal RNAs. AB - The nucleotide sequence of Pinus silvestyris 5S rRNA was determined using two independent methods and compared with other plant 5S rRNAs. It shows more than 90% sequence homology with gymnosperm 5S RNAs. The free energy (delta G) analysis of 5S rRNAs from gymnosperms, angiosperms and the other higher plants revealed that the free energy of this ribosomal RNA decreases with evolution. PMID- 2096906 TI - Ligand-induced conformational changes in cytosolic protein kinase C. AB - The changes in intrinsic spectral properties of protein kinase C were monitored upon association with its divalent cation and lipid activators in a model membrane system. The enzyme demonstrated changes in both its intrinsic fluorescence and far ultraviolet circular dichroism spectra upon association with lipid vesicles in the absence of calcium. The acidic phospholipid, phosphatidylserine, significantly quenched the intrinsic tryptophan fluorescence and was also the most potent lipid support for the phosphorylating activity of the enzyme. The enzyme was fully activated by a number of Ca2(+)-lipid combinations which correlated with maximal fluorescence quenching (40-50%) of available tryptophan residues in hydrophobic domains. The circular dichroism structure of the associated active-protein Ca2(+)-lipid complexes suggested different active enzyme secondary structures. However, the Ca2(+)-dependent changes in fluorescence and circular dichroism spectra were observed only after the enzyme associated with the lipid vesicles. These data suggest that protein kinase C has the properties of a complex multidomain protein and provides an additional perspective into the mechanism of protein kinase C activation. PMID- 2096907 TI - Photoresponsive peptide and polypeptide systems: 10. Synthesis and reversible photochromism of azo aromatic poly(L-alpha,beta-diaminopropionic acid). AB - Poly-L-alpha,beta-diaminopropionic acid) having azo aromatic side chain was synthesized by the water-soluble carbodiimide procedure. The photochemical properties of the azo polypeptide poly[N beta-p-(phenylazo)benzoyl-L-alpha,beta diaminopropionic acid] (PPABLDPA) was investigated by absorption and circular dichroism (c.d.) spectroscopy in hexafluoro-2-propanol (HFIP) and dimethylformamide. The photochromism of the absorption band in the visible and ultraviolet wavelength regions was found to be mostly reversible as a function of irradiation time at different wavelengths due to the photostationary state (88% trans)-cis photoisomerization of the azo aromatic moieties. The c.d. spectra exhibited two and three-stage photochromism on irradiation by light. The reversible photo-induced solubility change was also studied. On irradiation PPABLDPA is soluble under ultraviolet light (cis) and precipitates under visible light (88% trans) in HFIP-water. A discussion was presented that includes our previous results on this azo aromatic polylysine homologue series. PMID- 2096908 TI - Differential scanning calorimetric studies on bovine serum albumin: I. Effects of pH and ionic strength. AB - Using defatted and SH-blocked bovine serum albumin (BSA), the measurement of differential scanning calorimetry (d.s.c.) was performed in the range pH 3-11 and ionic strength 0.001-1 M. The shape of the d.s.c. curve was classified into four regimes: (i) the curve with no peak, (ii) that with a peak, (iii) that with a peak having a shoulder, and (iv) that with two peaks. The presence of two peaks was interpreted by the concept of 'heat-induced transition'. The BSA molecule is composed of two domains, thermodynamically independent owing to the formation of a crevice in BSA in a particular range of pH and ionic strength; this gives two peaks in the d.s.c. curve. The enthalpy (delta H) from the d.s.c. curve was plotted against pH and against the NaCl concentration. The value of delta H increased with the increase in the ionic strength in the pH range 5.6-9.0. The temperature of thermal denaturation (the temperature of the peak maximum, Td) was raised with the increase in the ionic strength in the pH range 4.5-9.0, but was lowered in the pH range 3.5-4.0. BSA was stabilized in the neutral-alkaline pH range by the presence of NaCl, but was destabilized in the acidic pH range. PMID- 2096909 TI - Effects of calcium and calmodulin antagonists on calpain II subunit conformations. AB - Only the 80-kD catalytic subunit of smooth muscle calpain II shows a change in intrinsic fluorescence on binding calcium, but both the 80-kD and 30-kD subunits show fluorescence changes in bound toluidinyl-naphthalenesulphonate as a result of calcium binding. Both subunits also show changes in intrinsic fluorescence in the presence of calmidazolium and felodipine. These studies indicate that both subunits have binding sites for calcium and the calmodulin antagonists, which are probably located in the calmodulin-like domain of each subunit. PMID- 2096910 TI - Circular dichroism of the non-enzymatic browning products of poly-L-lysine and albumin. AB - Poly-L-lysine (PLL) and bovine serum albumin were used as models in the investigation of non-enzymatic glycation and browning reaction by circular dichroism measurements. Different sugars (glucose, glucose-6-P and ribose) induced different extents of reaction and produced different chromophores that absorbed light in the near u.v. region. All glycated samples gave a common spectral feature in absorption and blue fluorescence, but they gave distinctly different near u.v. c.d. features, indicating that the browning products containing yellow chromophores are different for glycated samples and may have rigid moieties. The ribocated PLL (at pH 11.0, alpha-helix) and albumin were unable to convert completely to beta-conformation upon heating, indicating that browning reaction may have changed the tertiary structure. PMID- 2096911 TI - A brief guide to nucleic acid chemistry. PMID- 2096913 TI - Immunoconjugate design: a predictive approach for coupling of daunomycin to monoclonal antibodies. AB - There is increasing interest in the development of daunomycin-antibody immunoconjugates for the targeting of drug to specific cells or tissues. To this end, we have examined the factors influencing the synthesis of daunomycin monoclonal antibody conjugates linked covalently by an acid-labile cis-aconitic spacer (which is considered to aid drug release from immunoconjugates in the lysosomes and thus enhance their cytotoxic potential). A rapid and efficient procedure for the purification of drug from contaminants and stabilizers was first developed; conditions for the optimal preparation of cis-aconityldaunomycin were established; products were analyzed and identified by TLC and HPLC. The coupling of cis-aconityldaunomycin to antibody was accomplished by activating the modified drug with a carbodiimide before addition to antibody. Several factors were identified which influenced the efficiency of the conjugation; in particular, the compositional features of the antibody which determine its electrophoretic charge characteristics were of profound effect. However, by appropriate choice and control of buffer pH during conjugation, it was possible to define conditions resulting in the controlled substitution of antibody with drug. The consequent effects upon the cell-binding activity of immunoconjugates were established and related to the extent of substitution. The procedures described enable appropriate reaction conditions to be selected for the linkage of daunomycin to antibody (at set drug/antibody molar ratios) and in good yield, based upon consideration of the compositional and charge properties of the antibody. PMID- 2096912 TI - Labeling of human IgG with rhodium-105 using a new pentadentate bifunctional ligand. AB - We report the labeling of human gamma globulin with the 105Rh complex of a new pentadentate bifunctional ligand, 1,7-bis(2-hydroxybenzyl)-4-(p aminobenzyl)diethylenetriamine. Complexes of this ligand with 105Rh were prepared by refluxing rhodium carrier spiked with 105Rh at pH9 in bicarbonate buffer. The complex was treated with an excess concentration of thiophosgene to prepare the isothiocyanate derivative which was extracted into CHCl3. The CHCl3 extract was dried and dissolved in DMF and reacted with a borate solution of human gamma globulin. Labeling yields were generally high and varied from 73% to 93%, depending upon the concentration of human gamma globulin and the isothiocyanate derivative of the complex used. The overall recovery of rhodium activity varied from 59% to 75% without taking into account activity lost due to decay. The conjugation reaction was complete by 4 h. From 0.4 to 8.5 atoms of Rh could be incorporated per molecule of protein by this method. The activated isothiocyanate complex did not show any degradation when stored at room temperature for up to 4 days and then used for conjugation. PMID- 2096914 TI - Simplified method for conjugating macrocyclic bifunctional chelating agents to antibodies via 2-iminothiolane. AB - A one-step method for conjugating macrocyclic chelators to antibodies using the protein modification reagent 2-iminothiolane controls aggregation, maintains immunoreactivity, and produces consistent chelate/antibody ratios. Conjugation conditions have been investigated with the macrocyclic chelates 6-[p (bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N ',N",N"' tetraacetic acid and 2-[p-(bromoacetamido)benzyl]-1,4,7,10-tetraazacyclododecane N,N',N ",N"'-tetraacetic acid, with three different monoclonal antibodies. The bifunctional chelating agents are prepared by bromoacetylation of their amine precursors using a two-phase H2O/CHCl3 system, which improves product purity. PMID- 2096915 TI - Enzymatic solid-phase assay for biotin and a biotin-benzodiazepine conjugate. AB - A novel enzymatic ligand binding assay for biotin and its benzodiazepine conjugate is based on their binding to horseradish peroxidase-avidin conjugate (A P) followed by the uptake of biotin-unsaturated A-P onto polystyrene beads coated with biotin-BSA. The detection limit is 1.3 x 10(-16) mol per tube (300 microL) with a 3.3 x 10(-12) M A-P solution and varies with the conjugate concentration employed. The coefficient of variation for 10 repetitive assays of 10(-15) mol of biotin is 6.22%. PMID- 2096917 TI - Electrophilic analogues of daunorubicin and doxorubicin. AB - Daunorubicin (DNR) or doxorubicin (DOX) was modified with one of four "linker reagents" to produce electrophilic drug analogues for synthesis of bioconjugates. Synthesis and characterization of two new reagents [p-isothiocyanatobenzoyl chloride and 3-(p-isothiocyanatophenyl) propionyl chloride] are described here for the first time. Adding one of the new reagents, bromoacetyl bromide, or p (fluorosulfonyl)-benzoyl chloride in chloroform to an alkaline aqueous solution of DNR (or DOX) provided excellent yields of the corresponding, electrophilic 3' N-amide analogue. The DNR and DOX analogues were characterized by thin-layer chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy. Bioconjugates were produced with the electrophilic DNR or DOX analogues by mixing them with bovine serum albumin (BSA), mouse IgG, or a monoclonal antibody (OC125, which specifically binds to the CA125 antigen from human ovarian carcinoma). The relative reactivity of the 3'-N-substituents toward protein is p-(fluorosulfonyl)benzoyl greater than phenylisothiocyanato greater than bromoacetyl. Overall, the new phenyl isothiocyanate acid chlorides are superior to p-(fluorosulfonyl)benzoyl chloride or bromoacetyl bromide as reagents with which to produce electrophilic DNR or DOX analogues for conjugation with monoclonal antibodies. The bioconjugates DNR-OC125 and DOX-OC125 are selectively toxic to two human ovarian cancer cell lines in vitro (1) and bind with high specificity to human ovarian tumor sections (2) that express the CA125 antigen. PMID- 2096916 TI - Synthesis and tissue distribution of fluorine-18 labeled trifluorohexadecanoic acids. Considerations in the development of metabolically blocked myocardial imaging agents. AB - A versatile method for the synthesis of trifluoro fatty acids, potential metabolically blocked myocardial imaging agents, has been developed. Two trifluorohexadecanoic (palmitic) acids have been prepared [6,6,16 trifluorohexadecanoic acid (I) and 7,7,16-trifluorohexadecanoic acid (II)], each of which bears two of the fluorine atoms as a gem-difluoromethylene unit on the fatty acid chain (at C-6 or C-7) and the third at the omega (C-16) position. The metabolic stability of carbon-fluorine bonds suggests the gem-difluoro group may block the beta-oxidation pathway, while the terminal fluorine could be the site for labeling with fluorine-18. The convergent synthetic approach utilizes a 2 lithio-1,3-dithiane derived from 10-undecenal or 9-decenal, which is alkylated with the OBO (oxabicyclooctyl) ester of 5-bromopentanoic acid or 6-bromohexanoic acid, respectively. Hydroboration-oxidation and alcohol protection are followed by halofluorination to convert the 1,3-dithiane system to a gem-difluoro group. The third fluorine is introduced by fluoride ion displacement of a trifluoromethanesulfonate. This synthesis is adapted to the labeling of these trifluoro fatty acids with the short-lived radionuclide fluorine-18 (t1/2 = 110 min), with the third fluorine introduced as fluoride ion in the penultimate step. The radiochemical syntheses proceed in 3-34% radiochemical yield (decay corrected), with an overall synthesis and purification time of 90 min. Tissue distribution studies in rats were performed with I and II, as well as with 16 [18F]fluoropalmitic acid (III), [11C]palmitic acid, and [11C]octanoic acid. The heart uptake of the fluoropalmitic acids decreases with substitution, the 2-min activity level for 16-fluoropalmitic acid being 65% and that for both 6,6,16- and 7,7,17-trifluoropalmitic acids being 30% that of palmitic acid. Fluorine substitution results in some alteration in the retention of activity by the heart: 16-fluoropalmitate actually clears more rapidly than palmitate, but the two trifluoropalmitates (particularly 6,6,16-trifluoropalmitate, I) show somewhat slower clearance of activity, although the improvement of I over palmitate is only modest. There is considerable accumulation of activity in the bone after administration of the fluorine-18 labeled fatty acids, suggestive of metabolic defluorination. These results indicate that fluorine substitution alters the physicochemical properties of the fatty acid so that uptake by the myocardium is diminished. Furthermore, while the gem-difluoro substituents at C-6 and C-7 may block beta-oxidation, the chain-terminal radiofluorine substituent is subject to omega-oxidation that releases it as fluoride ion. PMID- 2096918 TI - Electrochemical investigations of the interaction of metal chelates with DNA. 3. Electrogenerated chemiluminescent investigation of the interaction of tris(1,10 phenanthroline)ruthenium(II) with DNA. AB - The electrogenerated chemiluminescence (ECL) that results from the oxidation of tris(1,10-phenanthroline)ruthenium(II), at a gold electrode in the presence of oxalate, was used to investigate the interaction of the Ru(II) chelate with calf thymus DNA. The decrease in ECL emission from the excited state, Ru(phen)3(2+*), in the presence of DNA, is ascribed to binding to binding of the chelate to the DNA strand. An ECL titration of the metal complex with DNA allowed determination of the equilibrium constant (K) and binding-site size (s) for association of Ru(phen)3(2+), under the assumption that only the free metal complex contributes to the observed emission. In 25 mM Na2C2O4, 2 mM phosphate buffer, pH 5, 0.05% Tween-20, 0.05% Triton X-100, regression based on the McGhee/von Hippel model, which accounts for free base pair gaps between binding sites, yielded K = 8.1 (+/ 0.2) x 10(3) M-1 and s = 4 bp. PMID- 2096919 TI - Antitumor activity of a thioether-linked immunotoxin: OVB3-PE. AB - A thioether-linked immunotoxin was made between Pseudomonas exotoxin and the monoclonal antibody OVB3. This conjugate, OVB3-PE, was cytotoxic for the human ovarium cancer cell line OVCAR-3 (ID of 2.5 x 10(-12) M) and it was therefore tested for antitumor activity in a nude mouse model of ovarian cancer. This model employs the injection of a lethal number of OVCAR-3 cells into the peritoneal cavity of nude mice. When 0.2-1 micrograms of OVB3-PE was injected intraperitoneally on three successive days beginning 3-5 days after OVCAR-3 cell implantation, the survival of the tumor-bearing mice was increased 2-4-fold compared to that of untreated control mice. Median survival times for control mice ranged from 44 to 50 days while survival times of 150 days or greater were seen in mice treated with OVB3-PE. When OVB3-PE administration was delayed until 2-4 weeks after tumor cell implantation, OVB3-PE treatment also showed antitumor activity, but the duration of survival was less than with the early treatments. OVB3-PE was also cytotoxic for MCF-7 breast carcinoma cells, HT-29 colon carcinoma cells, and A431 epidermoid carcinoma cells. PMID- 2096920 TI - Protein radiohalogenation: observations on the design of N-succinimidyl ester acylation agents. AB - In previous studies we have demonstrated that antibodies radioiodinated with N succinimidyl 3-iodobenzoate (SIB) are less susceptible to loss of radioiodine in vivo than antibodies iodinated directly by electrophilic substitution on their tyrosine residues with Iodogen. Since the Bolton-Hunter reagent, N-succinimidyl 3 (4-hydroxy-3-iodophenyl)propionate, is identical with SIB except that it contains a hydroxyl group on the aromatic ring and a two-methylene spacer, a comparison of their coupling chemistry and in vivo behavior was performed to better understand the structural requirements for a useful iodinated acylation agent. Protein concentration and pH had a significant effect on the coupling efficiency of both SIB and the Bolton-Hunter reagent; however, protein-labeling yields with SIB were generally higher by a factor of 2. Paired-label biodistribution studies in mice demonstrated that thyroid uptake (a monitor of dehalogenation) of antibody labeled by the Bolton-Hunter method was twice that of antibody labeled with SIB but only 7% of that observed for antibody labeled with Iodogen. These results suggest that even minor differences in iodination site can profoundly alter the retention of label on a protein in vivo. PMID- 2096921 TI - A conjugate of 5-fluorouridine-poly(L-lysine) and an antibody reactive with human colon carcinoma. AB - The ribose moiety of 5-fluorouridine (FUR) was oxidized with periodate and the product was bound through a poly(L-lysine) bridge to monoclonal antibodies, denoted SF25MAb, reactive with a human colon carcinoma LS180. The antibody was linked via its polysaccharide (previously oxidized with periodate) to the poly(L lysine)-drug conjugate. The linking of FUR-poly(L-lysine) to the antibody markedly increased the latter's binding to the tumor cells. A relatively lower increase was also observed with conjugates of nonrelated antibodies, such as anti hepatitis B surface antigen and anti-epidermal growth factor receptor antibodies. The pharmacological activity of the specific conjugate FUR-poly(L-lysine) SF25MAb was higher than that of the drug-substituted polymer alone. The poly(L lysine) bridge caused toxic effects in vivo, even though substituted both by FUR and by antibody. Therefore, the additional unreacted lysyl residues were blocked by succinylation. Partial blocking of free amino groups on the conjugate rendered it nontoxic but decreased its cell-binding capacity, though to a level still higher than that of the original unmodified antibody. The pharmacological activity of the specific conjugate after blocking was also reduced and necessitated prolonged incubation periods or higher concentrations. Following periodate oxidation and reduction, FUR was as effective as the clinically preferred compound 5-fluoro-2'-deoxyuridine in vitro and in vivo, against the LS180 colon carcinoma. Experiments in nude mice, with LS180 tumor subcutaneous xenotransplants, showed that FUR-poly(L-lysine)-SF25MAb (blocked by succinylation) was not toxic and was effective in the retardation of tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096922 TI - Succinylated polylysine as a possible link between an antibody molecule and deferoxamine. AB - Modification of antibodies with chelating polymers may be helpful for radioimmunoimaging, radioimmunotherapy, and NMR tomography. Succinylated polylysine was activated with carbodiimide/N-hydroxysulfosuccinimide in dimethyl sulfoxide and isolated as a dry solid. Sulfosuccinimide-esterified polymer was used for the two-stage coupling of an amino-containing chelating agent (deferoxamine) to monoclonal R11D10 (IgG) or its Fab fragment. Conjugates were separated from free components by using gel-chromatography and anion-exchange chromatography. Antibody-coupling efficiency and the loss of its immunoreactivity upon modification have been studied for polymers with different deferoxamine content. Specific binding of 67Ga to the corresponding antigen via the conjugate has been demonstrated. PMID- 2096924 TI - Longitudinal study of proteins in plasma and dialysate during continuous ambulatory peritoneal dialysis (CAPD). AB - The aim was to evaluate plasma proteins during continuous ambulatory peritoneal dialysis (CAPD) in relation to dialysis losses, membrane permeability, renal insufficiency, and time on CAPD. Ten male patients, established on CAPD for at least 14 months, were studied every 8 weeks for 56 weeks. Blood and dialysate from the morning exchange were analysed for urea, creatinine, and 7 proteins, and used to calculate dialysate to plasma concentration ratios (D/P). These ratios were not significantly changed suggesting that permeability remained constant. However, there was a trend for beta 2-microglobulin, creatinine, and urea to increase progressively. After 56 weeks, beta 2-microglobulin had increased from 27.9 to 31.3 mg/L (p less than 0.05) and creatinine 1006 to 1099 mumoL/L (p less than 0.05) and both correlated with time on CAPD (p less than 0.001). Plasma alpha 1-acid glycoprotein, albumin, transferrin, IgG, IgA, and complement C3 were not significantly changed, although IgA and complement C3 were each negatively correlated with time on CAPD (r = -0.70 and -0.67, respectively), creatinine (r = 0.51 and -0.54), and urea (r = -0.61 and -0.61) (p less than 0.001 for all). It is concluded that increases in beta 2-microglobulin, creatinine, and urea are not due to loss of membrane permeability but reflect a slight increase in uraemia. Long-term decreases in immunological proteins may be caused by uraemia or progressive depletion. PMID- 2096923 TI - The oxidative cleavability of protein cross-linking reagents containing organoselenium bridges. AB - The intensive use of cleavable cross-linking reagents to study macromolecular biological interactions has shown a demand for optimizing these reagents in such a way that the involved macromolecules remain intact. The present work focuses on the development of selenium linkers that are cleavable by mild oxidation. The efficiency of cross-linking and subsequent cross-linker cleavage with a new series of such homo- or heterobifunctional cross-linking reagents have been tested in a simple model system, consisting of albumin and cytochrome c. Resultant, or residual, covalent complex formation is examined by SDS polyacrylamide gel electrophoresis. From this work it can be concluded that diallyl selenides are readily cleaved by mild oxidation, whereas dialkyl selenides and benzyl alkyl selenides can only be cleaved when the alkyl part of the selenide has an electron-withdrawing group next to the beta-carbon from selenium. PMID- 2096925 TI - Factors predisposing and contributing to peritonitis during chronic peritoneal dialysis in children: a ten-year experience. AB - Factors contributing and predisposing to peritonitis were studied retrospectively in 83 children treated with continuous ambulatory (CAPD) or continuous cycling peritoneal dialysis (CCPD) from 1978 to 1988. Recurrent peritonitis was the most frequent complication and the major reason for peritoneal dialysis failure. Fifty patients had 171 episodes of peritonitis during the ten years and 33 remained peritonitis-free. The duration of dialysis was significantly shorter in the peritonitis-free group. The incidence of peritonitis was lower with CCPD than with CAPD. Leucopenia was not a predisposing factor nor was blood leucocytosis helpful in diagnosing peritonitis. Serum IgG was low in 33% of patients with episodes of peritonitis, but there was no correlation or predictive value in this finding. The C3 component of complement was relatively lower than the C4 but both components was relatively lower than the C4 but both components were usually in the normal range. Serum albumin was low in all patients, but lower in those with peritonitis episodes. Age, sex, primary disease, diapers, pyelostomies, dialysis training, and living conditions were not significantly associated risk factors. Sterile dressings gave no benefit over the shower technique. Patient noncompliance, upper respiratory tract infection, skin infections, and dental treatment were potential risk factors. However, peritonitis seemed to be distributed randomly among the patients. PMID- 2096926 TI - The management of hydrothorax in continuous ambulatory peritoneal dialysis (CAPD). AB - Four patients on continuous ambulatory peritoneal dialysis (CAPD) developed large, symptomatic pleural effusions after commencing peritoneal dialysis. Pleuroperitoneal fistula in each case was diagnosed by the presence of a high glucose content in pleural fluid, with a normal corresponding blood sugar, and was confirmed by isotope or contrast peritoneography. Two patients had their effusions drained percutaneously, and then underwent pleural sclerosis with intracavitary tetracycline. Two patients had a thoracotomy performed, of which no fistula was identified in one case, and the other patient underwent pleurectomy. All four patients successfully recommenced CAPD several weeks after therapy, without recurrence of effusions. We conclude that pleuroperitoneal connections associated with CAPD do not mandate cessation of peritoneal dialysis and conversion to maintenance haemodialysis. Definitive diagnosis requires aspiration of pleural effusions for glucose estimation. Contrast or isotopic peritoneography is helpful in localising the fistula, but in our experience did not alter management. Simple sclerotherapy is effective and avoids the need for a formal thoracotomy. PMID- 2096927 TI - Hematocrit values in the CAPD/CCPD population: a report of the National CAPD Registry. AB - A survey of the National CAPD Registry population was conducted to assess the distribution of hematocrit levels in a large group of peritoneal dialysis patients, to characterize the anemia of the population, and identify factors which relate to variation in hematocrit levels. A random sample of 812 patients was selected from the Registry population. Information was provided on 608 patients. Characteristics of sampled patients were similar to the Registry population as a whole. The mean hematocrit level in this cohort was 29.4% and the median was 29% Recent peritonitis, time on CAPD, folate therapy, androgen therapy, and iron therapy had no obvious influence on hematocrit distributions. Significantly higher hematocrits were seen in males, whites, and patients with polycystic kidney disease. Significantly lower hematocrits were seen in surgically anephric patients and in patients who had received transfusions 60 days before the survey. Eighty-nine percent of patients had not received a transfusion 60 days prior to the survey. Some patients, especially those with hematocrits below the median, might benefit from recombinant erythropoietin therapy. PMID- 2096928 TI - Hematocrit and residual renal creatinine clearance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). AB - In a recent report, the relationship between renal creatinine clearance and hematocrit in patients with renal creatinine clearances, ranging from 55 to 8 mL per min. per 1.73 square meters of body surface area, was analyzed. The authors of this study have performed a cross-sectional analysis of the relationship of hematocrit to residual renal creatinine clearance in patients on continuous ambulatory peritoneal dialysis (CAPD). The authors of this study wanted to examine whether or not these hematocrits fall within extrapolations of the published 95% confidence limits for males and females with renal failure prior to end-stage renal disease and dialytic intervention. Authors also compared regression intercepts at residual creatinine clearances of 0. Most of the CAPD patients had hematocrits within the upper half or above the extrapolated 95% confidence limits for the predialysis population. Within the CAPD population, there were no significant correlations of hematocrit with residual creatinine clearance at these lower ranges. The degree of scatter in the CAPD population for hematocrit values was similar to that in the predialysis population. Residual creatinine clearance appears to be a crude index of the increasing severity of multiple factors that may contribute to the anemia. CAPD appears to maintain or improve hematocrit as renal mass and function decline. PMID- 2096929 TI - Vancomycin absorption from the peritoneal cavity during dialysis-related peritonitis. AB - The uptake of vancomycin from the peritoneal cavity during acute episodes of peritonitis was compared to noninfected patients in 14 patients, 7 of whom had dialysis-related peritonitis. Treatment consisted of 8 hourly dialysate exchanges, followed by 4-h dwells containing 37.5 mg/L of vancomycin. On day 4, serum vancomycin concentrations were 13.4 +/- 4.8 mg/L in the controls and 15.5 +/- 6.8 mg/L in the group with peritonitis. After 180 min in the peritoneal cavity, 61% +/- 13% of the infused vancomycin remained in controls and 30% +/- 15% in patients with peritonitis (p less than 0.05). Uptake of vancomycin from the peritoneal cavity is enhanced during episodes of peritonitis. PMID- 2096930 TI - Stability of amphotericin B in CAPD fluid. AB - Amphotericin B is the drug of choice in continuous ambulatory peritoneal dialysis (CAPD) associated fungal peritonitis and is usually administered intraperitoneally. The drug is stated to be incompatible with anions. All CAPD fluids contain chloride and lactate anions. Therefore, the physical and chemical compatibility of amphotericin B with dextrose 5%, Dianeal 1.36% CAPD fluid, and Dianeal 1.36% peritoneal effluent was studied at amphotericin B concentrations of 1, 2, and 5 mg/L. Amphotericin B was most stable in Dianeal CAPD fluid. The rate of degradation was concentration dependent in dextrose 5% and peritoneal effluent. The higher the concentration, the lower the rate of degradation. After an incubation of 6 h at 37 degrees C, no significant decomposition was found at all concentrations studied in Dianeal CAPD fluid whereas 12-18% decomposition was found in effluent. No physical incompatibility with any solution was observed. PMID- 2096931 TI - Pharmacologic modification of transperitoneal movement of water. AB - Investigations concerning the influence of pharmacologic agents on transperitoneal water movement are predominantly undertaken in the hope that their results can help in a restoration of net ultrafiltration (UF) volume toward normal in cases with declining UF during long-term dialysis treatment. Net UF volume represents the difference between net transcapillary UF and lymphatic absorption. The choice of a pharmacological agent for enhancing UF depends on the mechanisms responsible for net UF loss, which include: (a) early dissipation of the transperitoneal osmotic gradient; (b) decrease in the peritoneal surface area; (c) lymphomonokine overproduction; (d) enhanced lymphatic absorption; (e) high residual volumes left in the peritoneal cavity; or (f) a combination of these factors. Leakage of dialysate to the abdominal wall sometimes occurring in peritoneally dialysed patients (1), according to a definition of net UF volume, cannot be regarded as a true UF loss. PMID- 2096932 TI - Tobramycin absorption from the peritoneal cavity. AB - Previous studies have found serum tobramycin concentrations greater than 8 mg/L among patients undergoing treatment for peritonitis using hourly dialysate exchanges containing 10 mg/L of tobramycin. In this study, tobramycin absorption from the peritoneal cavity was evaluated among patients treated with exchanges of 180 min. intraperitoneal duration. Six patients in each group were studied. Mass transfer coefficients [MTC (mL/min.)] were calculated for noninfected (C) and peritonitis (P) periods. The mean MTC for C was 6.5 +/- 2.1 (SD) mL/min., and for P, 18.5 +/- 8.2 (SD) mL/min. (p less than 0.01). Peritonitis increased the rate of uptake from the peritoneal cavity. In these acute studies, the total dose of tobramycin delivered was small, so that serum concentrations remained less than 0.2 mg/L among controls and 0.5 mg/L among patients with peritonitis. Prolonged exposure to tobramycin, in association with more rapid absorption from the peritoneal cavity, may lead to serum concentrations greater than 8 mg/L. PMID- 2096933 TI - Mechanical cardiopulmonary resuscitation choice of patients on chronic peritoneal dialysis. AB - Fifty-five adult patients (5 women, 50 men) on chronic peritoneal dialysis, mostly continuous ambulatory peritoneal dialysis (CAPD), for 2 to 155 mon were asked whether or not they wanted to have mechanical cardiopulmonary resuscitation (CPR) in case of sudden death. Thirty-five patients (65%) opted for CPR and 20 (36%) declined. Statistically, sex (although the number of women interviewed was too small for a valid sample) and duration of dialysis had no effect on choice of CPR, whereas older age, the presence of diabetes, advanced medical disability, and advanced socioeconomic disability were associated with a tendency to decline CPR. Among the 10 patients who had CPR, 5 developed flail chest, 4 had multiple rib fractures, and only 1 had no chest wall trauma from CPR. Two patients left the hospital alive. One third of the patients on chronic peritoneal dialysis do not want CPR. Advanced age, diabetes, and poor medical and socioeconomic states predispose peritoneal dialysis patients to decline CPR. PMID- 2096934 TI - Treatment of severe hypophosphatemia with intraperitoneal phosphate. PMID- 2096935 TI - Erythropoietin may improve the ultrafiltration in peritoneal dialysis: a case report. PMID- 2096936 TI - Tuberculous peritonitis in CAPD--a cause of hypercalcaemia. PMID- 2096937 TI - A simple method of preventing accidental disconnection at the peritoneal catheter adapter junction. PMID- 2096938 TI - Comparison of Cytur-test and Chemstrip LN for detecting neutrophils in CAPD effluents. PMID- 2096939 TI - Pharmacokinetics of intraperitoneal cefotaxime in children with peritonitis undergoing continuous ambulatory peritoneal dialysis. PMID- 2096940 TI - Alternaria peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis. PMID- 2096941 TI - Literature. October-December 1990. PMID- 2096942 TI - Substance abuse among American Indians in an urban treatment program. AB - Chart reviews were used to describe demographic and clinical characteristics of 68 urban American Indian people attending an Indian-oriented outpatient substance abuse treatment program in Denver, Colorado, and to describe program staff's assessment of client's response to treatment. Alcohol and marijuana were the drugs abused most frequently. The program admitted about equal numbers of males and females; age averaged 24 years. Although Colorado has only Ute reservations, 49% of clients were Sioux, while none were Ute. Moreover, 87% of clients were not active in Indian religion and culture. Clients had low educational achievement and very low income. Few were in stable marriages. In comparison to counselors, clients underestimated the severity of their problems. By counselors' assessment, 78% of clients did not finish the program, and only two fully achieved the treatment goals. Areas for further clinical research are suggested. PMID- 2096943 TI - Determinants of blood pressure in Navajo adolescents. AB - Hypertension is becoming more common among Navajo people, especially among young men. In a group of 580 Navajo adolescents, we looked for factors associated with variations in blood pressure level. Using our criteria, 11.1% of adolescent males and 1.6% of females had an elevated screening blood pressure. In males, blood pressure was a function of age only, and not significantly related either to obesity (body mass index) or measures of acculturation and personal adjustment. In females, blood pressure was not related to age, but was associated with body mass index. Systolic pressure in females was also associated with poor personal adjustment. Level of acculturation (by our index) had no bearing on blood pressure level in this population. PMID- 2096944 TI - The ethics of heroism in medieval and American Indian tales. AB - Oral-traditional stories detail their heroes' growth through a narrative pattern of exile and return that places the heroes in situations repeatedly challenging their strength and resolve. Through the motif of the quest, medieval and American Indian tales alike reaffirm general psychological truths that bear upon our understanding of human nature. Stories about heroes are stories about us: about our desires to grow up, to defeat death, to prove ourselves in difficult situations, and to achieve recognition or admiration among our peers (Becker, 1973, p. 4). In this way, medieval and American Indian tales are about self actualization. They maintain that "one has within oneself proclivity toward growth and unity of personality ... and an automatic thrust toward expression" of these qualities (Yalom, 1980, p. 9). All forms of literature, however, reflect ideas peculiar to their cultures. The ways in which these basic human truths are represented in medieval and American Indian tales suggest the differing religious or social concerns that have informed these truths and have given them shape. To a large degree, the medieval knight's view of "self" and "other" encompasses the view that Western humanity has had (and continues to have) of itself. This is a view conditioned upon the superiority of the "self" as measured against the inferiority of the "other," reinforced through existing social (hierarchial) and religious (Judeo-Christian) codes of behavior. Such codes are not only inadequate to the task of interpreting American Indian perceptions of "self" and "other," they are inimical to the ethical foundation underlying them. Scott Momaday remarks that "you cannot understand how the Indian thinks of himself in relation to the world around him unless you understand his conception of what is appropriate; particularly what is morally appropriate within the context of that relationship" (Basso, 1984, p. 46). For the American Indian hero, self actualization is self-transcendence. By "becoming a part of something greater" than himself, the American Indian hero sustains a moral vision that not only reveals his "latent nobility" but also protects, even strengthens, the relational fabric of his community. By reading these and other American Indian tales, Western healers may become more sensitive to the moral conflicts uniquely experienced by American Indians and to the needs of others who desire to revise or strengthen their own moral structures by including ideas of relatedness and relationship. PMID- 2096945 TI - A comparison of time Ojibway adolescents spent with parents/elders in the 1930s and 1980s. AB - This study compared quantity and quality of family time spent with parents/elders by American Indian Ojibway adolescents (ages 12-18) in the 1980s to Ojibway adults (ages 55-70) who were adolescents in the 1930s. Results indicated that 1980s adolescents spent an average of 12.5 hours per week with parents/elders compared to 62 hours per week indicated by respondents who were adolescents in the 1930s. The 1980s adolescents reported significantly more adult substance use and family abuse within their homes, and indicated significantly less favorable well-being responses than 1930s adolescents. PMID- 2096946 TI - [A comparative analysis of chromatographic, kinetic and antigenic properties of casein kinase type 2 from bovine liver and the phytopathogenic mushroom Verticillium dahliae]. AB - Homogeneous preparations of casein kinases 2 have been isolated from bovine liver and the phytopathogenic fungus Verticillium dahliae. The isolation procedure was similar in both cases and included consecutive chromatography on heparin Sepharose, phosphocellulose PII and monoQ. The bovine liver enzyme consists of two subunits with molecular masses of 38 kDa and 27 kDa, while the fungus kinase has three subunits with Mr of 53 kDa, 41 kDa and 38 kDa. Self-phosphorylation of casein kinase 2 in vitro resulted in phosphate incorporation into the smaller subunit of the mammalian enzyme and into all the three subunits of the fungal enzyme. The Km value of casein kinase 2 from bovine liver for ATP is 3.1 microM; that for GTP is 22.0 microM. The corresponding parameters of the fungal kinase are 14.3 and 18.2 microM, respectively. Specific antibodies to each kinase have been raised. The lack of antigenic cross-reactions between the two enzymes has been demonstrated by ELISA. PMID- 2096947 TI - [Functional characteristics of cytochromes P-4501A1 and P-4501A2 in rodent liver]. AB - Antibodies to mouse liver cytochrome P3-450 (anti-P3-450) and antibodies to rat liver cytochrome P-450d (anti-P-450d-c) inhibit the 0-deethylation of 7 ethoxyresorufin (ER) in liver microsomes of benz(a)pyrene-induced (BP) mice but do not inhibit the 0-deethylase activity in liver microsomes of BP-induced rats. Anti-P3-450 and anti-P-450c inhibit BP-hydroxylation in BP-induced mouse liver microsomes by 20%, but they do not inhibit this reaction at all in BP-induced rat liver microsomes. In a reconstituted monooxygenase system isolated cytochrome P3 450 metabolized 7-ER and BP. In contrast, its homologue, cytochrome P-450d, did not metabolize these substrates. The fraction containing cytochrome P1-450 metabolized 7-ER at a low rate and BP at a rate of 3.6 nmol product/min/nmol cytochrome. Western blot analysis with anti-P-450c + d revealed two bands in SDS PAGE gels containing BP-induced mouse liver microsomes. The interaction of mouse liver BP-microsomes with anti-P3-450 and anti-P-450d-c was accompanied by the appearance of a single band (cytochrome P3-450). PMID- 2096948 TI - [Isoelectric focusing of 3-hydroxy-3-methylglutaryl-CoA-reductase from the postmicrosomal fraction of rat liver]. AB - Using isoelectrofocusing, the existence of multiple forms of 3-hydroxy-3 methylglutaryl-CoA reductase (EC 1.1.1.34) in the postmitochondrial fraction of rat liver has been demonstrated for the first time. The isoelectric points for the enzyme isoforms are 6.25, 7.5 and 8.25. PMID- 2096949 TI - [Study of the affinity characteristics of monoclonal antibodies by solid-phase immunoenzyme analysis]. AB - An approach is proposed for measuring the binding constant (Kb) for monoclonal antibodies (MA) interacting with an immobilized antigen in indirect ELISA. This approach allows the measurement of optical density (A405) in the peroxidase reaction initiated by the conjugate at different concentrations (C0) of antibodies. Using the Scatchard plots, the dependence of A405/C0 = f (A405) for the whole range of MA concentrations was examined, and the tangential of the slope (tg alpha = Kb) of the linear portion of the antigen molecule was calculated. Analysis of MA affinity parameters by using this approach may find wide use in immunodiagnostic studies aimed at measuring antigen and antibody concentrations in biological fluids as well as for estimating the efficiency of vector drugs in which the diagnostic or therapeutic component is conjugated with the vector (MA or F(ab) fragment) responsible for the drug transport to target cells. The method proposed was used for testing mouse (BALB/C) monoclonal antibodies (IgG1) to pig insulin produced by various hybridomas as well as for estimating the effect on MA of pH, temperature and hydrophobization. The minimal detectable concentration (method sensitivity) was found to depend on Kb. PMID- 2096950 TI - [Comparative study of aromatic ring meta-cleavage enzymes in Pseudomonas strains with plasmid and chromosomal genetic control of the catabolism of biphenyl and m toluate]. AB - It was shown that two different enzymes of aromatic ring oxidative meta-cleavage (2,3-dihydroxybiphenyl-1,2-dioxygenase), DBO and catechol-2,3-dioxygenase, C230) function in Pseudomonas strains with a plasmid and chromosomal genetic control of biphenyl and toluate catabolism. A comparative analysis of DBO's and C230's expressed by the pBS241 biphenyl degradative plasmid in P. putida BS893, pBS311 in P. putida U83, chromosomal genes in P. putida BF and C230 from P. putida PaW160 (pWWO) was carried out. It was found that the DBO's of all strains under study are highly specialized enzymes in respect of 2,3-dihydroxybiphenyl cleavage and are also able to cleave 3-methyl-catechol and catechol (but not 4 methylcatechol) at low rates. In contrast with DBO's, in Pseudomonas strains the substrate specificities of all C230's are variable. The C230's expressed by the D plasmids pBS241 and pBC311 have a moderate affinity for catechol, 3-methyl- and 4 methylcatechol, but are unable to cleave 2,3-dihydroxybiphenyl. The C230 which is encoded by the chromosomal structure gene from P. putida BF is very similar to C230 which codes for the TOL-plasmid pWWO. These plasmid differ from C230's expressed by biphenyl D-plasmids due to their capability to cleave 2,3 dihydroxybiphenyl in addition to catechol cleavage. All DBO's and C230's under study possess a number of properties that are typical for the enzymes having an oxidative meta-cleaving effect. The different roles of these enzymes in biphenyl and toluate catabolism in Pseudomonas strains are discussed. PMID- 2096951 TI - [Chemical modification of rabbit immunoglobulin G by dansylaziridine and study of the properties of modified antibodies]. AB - To elucidate the effect of the antigen binding fluorescent thiol reagent, N dansylaziridine (DAZ) which is sensitive to microenvironmental changes, was used for modification of the rabbit IgG hinge region cystine residue. DAZ binds to the hinge region Cys 226 as could be evidenced from the structural analysis data. Labelling of IgG with DAZ does not alter either its conformation and hydrodynamic behaviour or its antigen binding properties. Upon antigen binding the fluorescence intensity of modified IgG increases up to about 80%. This finding suggests that the interaction of antibodies with the antigen is accompanied by conformational changes in the IgG hinge region. PMID- 2096952 TI - [Intracellular aminopeptidase from Xanthomonas rubrilineans, hydrolyzing alpha amino acid esters and cefalexin]. AB - The aminopeptidase was isolated from cell-free extracts of Xanthomonas rubrilineans by protein precipitation by isopropyl ester with subsequent purification by affinity chromatography on CABS-Sepharose, bacitracin-Sepharose, gel filtration through Sephadex G-200 and ultrafiltration, the total yield being 32% with 2200-fold purification. The enzyme was homogeneous during SDS-PAAG electrophoresis. Apart from the broad spectrum of the peptidase activity, aminopeptidase possesses a hydrolase activity towards beta-lactam antibiotics and an esterase activity towards L- and D-amino acids. Besides, this enzyme catalyzes the acetyl transfer reaction during cephalexin synthesis from the D-phenylglycine ester and 7-aminodesacetoxycephalosporanic acid. The maximal enzyme activity during L-Ala-pNA and cephalexin hydrolysis is manifested at pH 6.5. The enzyme is stable at pH 4.0-8.0 and is inhibited by o-phenanthroline, p chloromercuribenzoate, hydrogen acetate and N-bromosuccinimide. The molecular mass of the enzyme is 270-280 kDa. The enzyme is a tetramer; the molecular mass of each of its four subunits is 70 +/- 2 kDa. The isoelectric point for the enzyme is 6.8. The amino acid composition of the enzyme appears as follows: Asp63, Thr33, Ser32, Glu72, Gly55, 1/2Cys3-4, Val45, Ile24, Leu53, Tyr23, Phe24, Lys23, His16, Arg36, Pro60, Met25, Ala55. PMID- 2096953 TI - [Regulation of thyroid hormones of the interaction of mitochondria with low molecular weight cytoplasmic mediators, induced by phosphate- dependent transport of K+ and H+ ions through the mitochondrial inner membrane]. AB - In vivo thyroid hormones control the binding to mitochondria of low molecular weight water-soluble cytoplasmic mediators that are capable to induce oxidative phosphorylation uncoupling, by increasing the sensitivity of mitochondria to the effects of these mediators. In hyperthyroid rat liver mitochondria cytoplasmic mediators stimulate the phosphate-dependent transport of K+ and H+ in a greater degree than in liver mitochondria of control rats. The increase in the oxidative phosphorylation uncoupling by cytoplasmic mediators is one of mechanisms of thermogenesis stimulation by thyroid hormones. PMID- 2096954 TI - [The effect of media pH and autocatalytic phosphorylation on the interaction of kinase phosphorylase with calmodulin]. AB - Using calmodulin covalently labeled with dansyl, the Ca2(+)-dependent interaction of phosphorylase kinase with calmodulin has been studied. It has been shown that at pH 6.8 the (alpha beta gamma delta) protomer of the enzyme binds 2.1 +/- 0.8 mol of calmodulin with Kd = (6.67 +/- 1.77).10(-8) M. The enzyme activation induced by the pH increase up to 8.2 does not affect the enzyme interaction with calmodulin [2.14 +/- 0.58 mol calmodulin per mol of (alpha beta gamma delta)]; Kd = (4.14 +/- 1.22).10(-8) M. However, the enzyme activation during its autocatalytic phosphorylation eliminates this effect practically completely. PMID- 2096955 TI - Effect of interchanging two composite resin system with a dentine adhesive. AB - There is a tendency to interchange dentine adhesives and composite resins when using composite resins for restorations. This study used marginal contraction gaps to test the effect of changing composite resins with a dentine adhesive. Cylindrical butt-joint cavities were prepared entirely in dentine using extracted human teeth. Two groups of control cavities (30 cavities per group) were restored with Prisma-Bond/Prisma-Fil and Heliobond/Heliomolar respectively. Two groups of test cavities (30 cavities per group) were restored using the dentine adhesive. Prisma Universal Bond with Prisma-Fil on one group and Prisma Universal Bond and Heliomolar in the other. Following thermocycling the marginal contraction gaps were measured and assessed. The results showed a significant reduction in marginal contraction gaps when using either composite resin with Prisma Universal Bond. This indicates a compatibility of both resins with the adhesive in this instance. PMID- 2096956 TI - Immunology of chronic generalized periodontitis. 1. Estimation of cellular and humoral immune status. AB - Cell-mediated and humoral immune responses were assessed in forty patients with chronic generalized periodontitis (CGP), and in an equal number of control subjects. The cell mediated immunity assessed by enumeration of total rosette forming cells [TRFC] and high affinity rosette forming cells [HARFC], were found to be slightly depressed in CGP patients compared controls. The humoral immune response was assessed by estimation of serum immunoglobulins G,A,M,D and E by single radial immunodiffusion technique (RID). Except IgD all the other immunoglobulins were found to be elevated significantly. These immunological derangements found in CGP patients may be the cause or effect of the disease process. PMID- 2096957 TI - Efficacy of various eugenol and non-eugenol root canal sealers in the treatment of teeth with periapical radiolucent area--a clinical and radiological study. AB - A clinical and radiological study was conducted to compare the efficacy of various eugenol containing Viz. Zinc oxide eugenol, CRCS and Rosen's Cement and non eugenol containing sealers and N2 on forty eight non-vital anterior teeth, with a periapical radiolucent area of 1-7mm in diameter. The patients were recalled after 30,90,150 and 210 days On radiological examination after 210 days CRCS showed maximum decrease in periapical radiolucency from 4.39 mm. to 1.80mm. The teeth treated with N2 as root canal sealer showed minimum decrease in the periapical radiolucency from 3.0 mm. to 2.15mm. On clinical examination the results were 100% successful in both the eugenol and non-eugenol groups. The radiological findings indicate that the eugenol containing are better as compared to non-eugenol containing root canal sealer. Out of eugenol containing root canal sealers CRCS showed maximum decrease in radiolucency and from non-eugenol containing group N2. PMID- 2096958 TI - Reasons for choice of dentistry as a career in Calcutta: a survey report. AB - A survey was carried out on a randomly selected student sample among the students of Dr. R Ahmed Dental College & Hospital, Calcutta to find out the main reasons for dentistry for a career. The main aim of the survey was to provide base line data on the topic. The reply rate was 71%. Among the sample, 71% chose dentistry as a second choice of career making. Only 5% were influenced by their dentists regarding their choice. 79% of the students were not well aware about the profession prior to admission. That dentistry offers a specialized profession was the commonest reason for its choice of a career. There were significant difference among males and females with respect to reasons other than the main ones. Further studies have been suggested and a need to popularise the profession among the potential applicants has been suggested to increase the applicant pool for dentistry. PMID- 2096959 TI - Orofacial manifestations of myofascial pain dysfunction syndrome amongst dental patients. AB - Orofacial manifestations in cases of Myofascial Pain Dysfunction Syndrome (MPD) diagnosed amongst 71 Dental patients were studied in detail. Findings of this study show that the chief complaint and associated orofacial manifestations of MPD are related to muscular hypertonicity. Stressful situations may produce muscular hypertension, which leads to muscle tenderness as a symptom of over work and fatigue. MPD may be considered a psycosomatic disease. PMID- 2096960 TI - Serological investigation of refractory human adult periodontitis. AB - This study examined the difference between the serum antibody profiles in refractory adult periodontitis patients (group A), and compared to those (group B) who responded well to conventional periodontal treatment. The levels of specific IgG antibody to Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, Fusibacteriumnucleatum, and Eikenella corrodens were assessed in a group of 19 patients (group A) and 11 patients (group B). Specific IgG serum antibody levels were estimated using biotin-avidin linked immunosorbent assay (BALISA). Results indicated that Actinobacillus actinomycetemcomitans, and Bacteroides gingivalis had very high levels of specific circulating antibody in the sera of both groups of patients; whereas, Fusobacterium nucleatum and Eikenella corrodens showed considerable lower levels of antibody than the other two antigens. However, the differences between the two groups with regard to the antibody levels against different bacterial antigens were not statistically significant. PMID- 2096962 TI - Biogenic amines in human gingiva in healthy and inflamed states. AB - As inflammatory disturbance are of significance in every aspect of periodontal disease, it was deemed pertinent to conceive on experimental study exploring the existence and relationship of biogenic amines, at least in the inflammatory gingiva. Gingival samples from 50 human individuals representing varying grades of inflammatory involvement have been utilised in the present work. From the results of this study, it could be elucidated that biogenic amines (noradrenaline, dopamine and 5-hydroxytryptamine) should show elevated concentration in inflammatory states of the gingiva. Further, these amines turnover was confirmed by studying monoamine oxidase which is a catalyzing enzyme of noradrenaline and 5-hydroxytryptamine; and 5-hydroxy indole aceticacid is a metabolic end product of 5-hydroxytryptamine. This was of a transitory nature indicating increased levels at the early stages of inflammation followed by a decrease at the peak of the gingival inflammation. It is assumed that biogenic amines helps in regeneration of connective tissue of the oral mucosa during the initial development of inflammation rather than final stages of the process, thereby emphasizing its transitory role in the inflammatory process. PMID- 2096961 TI - Cholinergic components in human gingiva in healthy and inflamed states. AB - Acetylcholine (ACh) and acetylcholinesterase (AChE) are main components in cholinergic nervous system. ACh is a natural constituent of many parts of the nervous system and its chief role is neurotransmission. It is not entirely unique in function to the cholinergic tissues of the human body. Gingiva is the part of the oral mucosa which contains numerous mast cells. They contain a variety of biologically active substances including neurotransmitters such as 5 hydroxytryptamine, histamine etc. In the dental literature accessible to authors no data were found on ACh and AChE in the different oral structures in health and inflamed conditions. Therefore gingiva samples from 50 human individuals representing varying grades of inflammatory involvement have been utilised in the present study. ACh and AChE were estimated in the gingiva tissues by flurometric and spectrophotometric methods. This study established hithero unknown "norms" for the ACh and AChE contents of the clinically normal gingiva, which are found to be 0.85 +/- 0.06(SE) ug/g and 210 +/- 18(SE) micromoles ACh hydrolysed/hr/gm/wet tissues. Results also revealed that the range of variations of ACh is high and AChE is low in all the inflamed states of gingival tissues. PMID- 2096963 TI - Evaluation of methyl cellulose as controlled release matrix material. AB - The formulation for the controlled release of NaF from matrix tablets using Methyl cellulose to prepare chewable NaF tablets for the prevention of dental caries is developed. Various micromeritic studies of granules and tablets containing different concentrations of matrix were studied. Dissolution studies were also carried out in distilled water at 37 +/- 1 degrees C. Significant variations in granule and tablet characteristics were observed depending upon the concentration of the Methyl cellulose used observed. The in vitro drug release reveals that, T 80% values for 30% concentration of matrix is greatest, which seems to be ideal concentration. The drug dissolution is diffusion controlled and follows the Higuchi equation. The fraction of the drug release is proportional to time 1/2 Clinical study is in progress and is encouraging. PMID- 2096964 TI - [Deinstitutionalization, the patients, the families and women: interests to reconcile]. AB - Deinstitutionalization is very demanding for families. Forced to fill in the gaps of the system, their role is one of creating a therapeutic environment while receiving little support from government service organizations. Cohabitation often leads to difficult relations between a patient and his or her family. In such a context, a large proportion of families experience problems in their attempt to fill their parental role. Women are more affected by this situation seeing they provide a large part of the emotional support to chronically ill mental patients and maintain the contact with service organizations. Also, they must confront professionals who often judge them as overprotective or responsible if the patient is their own child. The authors definitely agree that collective responsibility must complement family responsibility to ensure the respect of patients', families', and women's rights. PMID- 2096965 TI - [The autonomy of women: some reflections-statements on the goal]. AB - The author reflects on women's reproductive autonomy and raises questions on the true significance of advancements in feminism in recent years. Does today's context of social interaction between sexes not promote a biologistical femininity characterized by a negative perception of the feminine body and of its reproductive potential? Does women's "liberation" not imply the rejection of the feminine body and of its difference? In order to avoid the perverse effects of the search for autonomy, it is not more appropriate to redefine the feminine body with reference to women instead of with reference to the male universe, as it seems to be the case today? PMID- 2096966 TI - [And if we speak about men?]. AB - This article raises questions about some of the perverse effects of the reasoning behind correlations between sex and health in our socio-cultural context. Such a reasoning strongly denounces the psychosocial problems of women, but tends to forget the vulnerability of men which is nonetheless clearly evident in official statistics on suicide, dependence on alcohol and other drugs, violence and itinerancy. PMID- 2096967 TI - [A new space for feminine desire]. AB - Psychoanalitical literature evolved around the idea of a space for desire structured according to the boy-mother relationship model. Is the feminine clinical approach, together with the historical contribution of feminism, discovering a new space for feminine desire? The psychotic female, for whom the role of the father has no meaning in the mother's discourse, refuses the Law as a symbol of social authority. As for the hysteric female, she does not rely on the Father as a safeguard against the emptyness that lies behind the Laws and the beliefs of men. In its own way, feminism adopts these positions of psychotic rejection and hysteric contestation by projecting them on to the social landscape. Furthermore, feminism requires new forms of social interaction that embody the esthetical space women need to experience life as full-fledged citizens. PMID- 2096969 TI - [Go take care of yourself, your factory is sick: the place of mass hysteria in the problem of women's health at work]. AB - Mass hysteria is defined as the epidemic occurrence of a series of physical symptoms in the absence of organic disorder and identifiable pathogen agents. In spite of substantial individual and contextual variations, there are striking similarities that unite the different episodes reported in the literature: existence of a triggering event, progression and rapid regression of unrelated symptoms, and cases involving predominantly women. The authors summarize research in that field and discuss the overrepresentation of women through hypotheses linked with: 1) biology and the weight of differential socialization of women and men; 2) the poor evaluation of environmental, organizational and ergonomical risks in areas where mass hysteria is witnessed. Feminist interpretation tacitly confronts the preconcept notion of feminine vulnerability in order to shed light on the fact that women's adverse working conditions are indeed underestimated. PMID- 2096968 TI - [Masculine inexpressiveness: myths and facts]. AB - This article examines the common admission that men express their emotions less than do women. Research data shows little difference between the behaviours of boys and girls before adolescence. During adulthood, however, evidence points to men being less expressive than women except in situations involving aggressive behaviour. Men's diminished expressiveness is apparent in a context of intimate interaction. But in situations where they compete for social status, men seem more likely to express emotions. The authors suggest that more studies take into account the social contexts of emotional expressiveness generated by division of labor based on sex. PMID- 2096970 TI - [10 years of feminist intervention in Quebec: statement and perspectives]. AB - The authors start off by reviewing the origins and principal characteristics of feminist therapy as it appeared in the United States at the end of the 1960s. Following this step are analyzed the conditions for the emergence of feminist intervention in Quebec and its specificity, terms commonly used by Quebec practicians when describing their work among women. Emphasis is placed on the analysis of feminist intervention in institutional environments due to its remarkable development over the last few years. The article concisely presents the two main theoretical approaches that inspire the intervention, namely the socio-behavioral approach and the awareness approach. Following a brief overview of feminist intervention in Quebec, the authors raise questions about its future. PMID- 2096971 TI - [Feminism and interventions with women; an experience with female alcoholics and drug abusers at Domremy Trois-Rivieres]. AB - With the advent of feminist ideology, women believed they could fashion made-to measure tools to end their oppression and emancipate themselves. However, passing from ideology to practice has led to a certain number of difficulties. On the other hand, the feminist viewpoint has made a major and undeniable contribution to society. This article discusses the trials and tribulations as well as the successes of feminist practice. PMID- 2096972 TI - [Alcoholism, mental health and homosexuality: 3 female lesbian cases]. PMID- 2096973 TI - [Support for persons caring for aged persons with loss of autonomy: a group intervention, an alternative? Presentation of a research project in the Lanaudiere region]. PMID- 2096974 TI - [Conception of an information system in mental health organizations in the Haut Richelieu territory]. PMID- 2096975 TI - [In praise of mediocrity ... a little mental health exercise for the forty year old on the edge of burnout]. PMID- 2096976 TI - [A study of suicidal tendencies in adolescents in the secondary level]. AB - A study carried out among 2,850 Quebec adolescents, aged 12 to 18 and coming from four high schools in the Trois-Rivieres area, shows that 15.4% of them admit to having seriously thought of committing suicide. These teenagers are at different stages of the suicidal process. Hence, 4% admit to nurturing serious thoughts about suicide: 7.9% say they are at the planning stages and 3.5% have actually attempted suicide. The characteristics of the families involved are fairly the same for all categories of suicidal tendencies. However, the fathers of the youth who have made attempts have less schooling than the father of the other teens with suicidal tendencies. Furthermore, the adolescents who have attempted suicide report a greater number of events that are key to their suicidal thoughts. The persistence of suicidal thoughts, the depressive state, the feelings of an existential void and the despair all grow in function of the seriousness of suicidal tendencies. These affective-type variables best distinguish the different categories of suicidal tendencies. PMID- 2096977 TI - [By way of a preface: the construction of the I/WE in women]. PMID- 2096978 TI - [Suicide and social policy in Quebec]. AB - Starting from three documents published by organizations set up by the Quebec government, the author examines how the government intends to give direction to and build a framework for social intervention in the area of suicide. The article looks at the fate that social policies could and, according to the author, should reserve for suicide. The author argues for an approach that fully recognizes the social dimension of suicide and that emphasizes primary prevention as well as government support for an autonomous community network that would have equal footing with the public network. PMID- 2096979 TI - [Women and the mental health policy]. AB - This article analyzes Quebec mental health policy from a feminist point of view. The critique focuses on the decyphering of three tacit premises that the author describes as wanting. On the base of these premises, the author argues that the policy avoids differences in sex and in gender role and their impact on mental health/disorders, that it belongs to a "naturalist" trend that wants to benefit families through the social integration of psychiatrized patients, and that it offers a scuttled partnership with women's groups. The author concludes by pointing out the policy's limits and dangers for women and women's groups, and by raising the issue of the relationship feminist services maintain with the State. PMID- 2096980 TI - [The feminist movement and mental health: what is left of our loves?]. PMID- 2096981 TI - [Women and family policy between ambivalence and implication]. AB - The eighties mark the Quebec government's setting up of a family policy. But all the facts indicate that this policy wavered between a family policy, a birth policy and a population policy. Women's groups and feminists, already reticent in dealing with traditional family and maternity institutions, were possessed with somewhat of an ambivalent attitude towards these policies mostly because of their fear of being trapped and undermined. All in all, it's the will to disseminate their point of view and to defend their interests that motivated women to get involved in these debates. The article concludes by advancing principles that should promote a family policy that is more sensitive to women's interests. PMID- 2096982 TI - Merozoite selection of erythrocytes by age and the induction of protective immunity. PMID- 2096983 TI - Three-dimensional reconstruction of the feeding process of the malaria parasite. AB - The use of serial sectioning followed by three-dimensional (3D) reconstruction is a convenient way to study the spatial morphology of any structure (organ, cell, organelle). This method was applied to the study of the feeding mechanism of some strains of murine and human Plasmodium and enabled clarification of morphological features of this process. The feeding and digestive system of Plasmodium is polymorphic: in single sections, it shows rounded or elongated vesicles or vacuoles of very different sizes and content. The 3D reconstruction allowed us to describe the phenomenon both in space and in time. The contents of the host cell are taken up through the cytostome to form a sausage-shaped cytostomal tube. Individual digestive vesicles are either pinched off from the terminal portion of the tube or by the individualization of the different portions of the tube itself. The cytosomal system can be made of several tubes or vesicles always originating from cytostomes that can disappear when the tube is fully developed. A second feeding mechanism is also observed. Smaller vesicles are formed from the cytostomal vacuoles or tubes, or from the surface of the so-called "food vacuole, " or from the whole erythrocyte/parasite interface. Very few differences appear when the different strains are compared. In the chloroquine-resistant strain of P. berghei or in the P. falciparum FCR3 strain, there appears to be a large increase in the number of cytostomal vesicles, with several functional cytostomes in P. falciparum. The chronology of the appearance of the two systems is comparable between the different species except in P. falciparum, where the pigment vesicles fuse together very rapidly to form a large residual vacuole with which the subsequently formed and degraded digestive vacuoles fuse. PMID- 2096984 TI - Intra- and extracellular routing in P. falciparum. PMID- 2096985 TI - Heterogeneous and substrate-specific membrane transport pathways induced in malaria-infected erythrocytes. PMID- 2096986 TI - The role of calcium ions in the invasion of Plasmodium falciparum. PMID- 2096987 TI - Is the increased erythrophagocytosis of malaria-infected variant erythrocytes due to early expression of normal senescence markers or to the formation of new and specific removal markers? PMID- 2096988 TI - The role of reactive oxygen intermediates in vitro and in vivo: some comments. PMID- 2096989 TI - Tumor cell adhesion to frozen lymph node sections--a correlate of lymphatic metastasis in breast carcinoma models of human and rat origin. AB - The role of tumor cell adhesion in lymphatic metastasis of breast cancer was investigated in vitro using a rat mammary carcinoma model of four cell lines with different metastatic phenotypes, two human breast cancer cell lines, and cryostast sections of normal rat or human lymph nodes, respectively. A positive correlation was found between the adhesion levels obtained with three metastatic rat mammary cell lines (TMT-081 greater than MT-100M & TMT-50) and a non metastatic line MT-W9B, the latter being 3-4 fold less adhesive to the lymph node sections than the metastatic tumors. This selective adhesion was specific, as it was not found with cryostat sections of rat liver and brain. Enzyme assays indicated that cell surface glycoproteins bearing terminal beta-galactoside residues were involved in the adhesion of the rat tumors. Adhesion of the human breast carcinoma cells Hs578T to sections of human lymph nodes was significantly higher than that of the normal breast epithelial cell line Hs578Bst, and comparable to adhesion of a second breast carcinoma line, MCF-7. Moreover, Hs578T cells isolated from regional lymph nodes of tumor-bearing nude mice were significantly more adhesive to human lymph node sections than the parental line. Adhesion of both human and rat tumors could be partially blocked by the addition of the synthetic peptide GRGDSPK and by antibodies directed to the beta 1 chain of integrin, suggesting that an integrin receptor may played a role in the adhesion. The results suggest that tumor cell adhesion to cryostat sections of lymph nodes is a correlate of the malignant phenotype in mammary tumors of diverse origins, and could be used to delineate the adhesion factors mediating lymphatic metastasis. PMID- 2096990 TI - Cultured cell lines from human breast cancer biopsies and xenografts. AB - Eighty-five breast cancer specimens were processed as part of a program in tumor acquisition, propagation, and preservation for biotherapy. Nine long-term culture cell lines were developed. Four cell lines were from solid tumor metastases, two lines were from pleural fluid specimens, and three were from xenograft tumors grown in nude mice. Two of the xenograft-derived cell lines were from biopsies which produced tumor cell lines as well. Success in establishing cultures did not correlate with the viability of the biopsy received. Poor tumor cell attachment to culture plastic was the most common problem. For certain specimens, attachment and growth were enhanced on collagen and extracellular matrix substrates. Collagen was beneficial in the development of one cell line. The cell lines were characterized and each of the lines contained more nuclear DNA than found in normal cells. Four of five lines tested were tumorigenic in nude mice. Five of nine were clonogenic in soft agar. Each of the cell lines tested reacted with at least two anti-tumor monoclonal antibodies. Xenograft and biopsy-derived cell lines from the same tumor were similar in their characteristics. While breast cancers are indeed difficult to establish and propagate in culture, the use of xenografts and special substrates appears to be beneficial in the development of cell lines from some tumors. PMID- 2096991 TI - Phase II study of deoxydoxorubicin in previously untreated metastatic breast cancer. AB - With the objective of identifying new chemotherapeutic agents active against breast cancer, we administered the phase II agent deoxydoxorubicin (DxDx) to 25 patients who had received no prior chemotherapy for their metastatic breast cancer. A dose of 30-35 mg/M2 given at 3 week intervals resulted in a response rate of 12%. The patients were subsequently treated with a combination of 5 fluorouracil, methotrexate, vincristine, cyclophosphamide, and prednisone. A response rate of 38% was achieved with this combination as second line therapy. Toxicity of DxDx was predominantly hematopoietic. One patient developed congestive heart failure. Median survival from onset of treatment with DxDx was 39 weeks. DxDx appears to be minimally active against metastatic breast cancer. Whether the administration of phase II agents as first line therapy offers an advantage in the overall management of metastatic cancer, needs further evaluation. PMID- 2096992 TI - Adriamycin effects on hydroperoxide metabolism and growth of human breast tumor cells. AB - Human breast tumor cells MCF-7 were grown during 5 days in the presence of Adriamycin and the IC50 was 50 nM with the highest sublethal concentration 0.1 microM. At this latter concentration Adriamycin produced a complete inhibition of cell division and a partial reversion to a normal breast epithelial appearance. Similar effects of Adriamycin were observed in cells cultured in the presence of 10% FBS and in a chemically defined medium, with Se-glutathione peroxidase activities of 3.8 and 1.3 U/mg of protein, respectively. Cell size and cell oxygen uptake were increased by 41% and by 50%, respectively, in Adriamycin treated cells. The spontaneous chemiluminescence of monolayers of intact MCF-7 cells (81 +/- 9 cps/mg protein) was increased by 48% in the Adriamycin-treated cultures (120 +/- 11 cps/mg of protein) in agreement with a 91% higher concentration of malondialdehyde in the same cultures. Adriamycin treatment produced a 71% increase in the steady state concentration of H2O2, which was estimated assuming diffusion equilibrium with the external medium, from 1.38 microM in the control cells to 2.38 microM in the treated cells. Cyanide insensitive respiration was also higher in the cells exposed to the drug than in the control cells. Adriamycin did not affect the activity of the antioxidant enzymes, Cu-Zn and Mn-superoxide dismutase, Se and non-Se-glutathione peroxidase, and catalase. These results contribute to the current hypothesis that oxygen free radicals produced by Adriamycin redox cycling are responsible for at least part of the cytotoxic effects due to this drug. PMID- 2096993 TI - Progesterone antagonists block the growth of experimental mammary tumors in G0/G1. PMID- 2096994 TI - Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer. AB - The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15 3, another member of the human mammary epithelial antigen family. Serum BCM was evaluated in 151 and CA 15-3 in 134 patients with breast cancer, in 30 normal controls, in 9 pregnant women, and in 13 cancer patients (non-breast). Neither the normal controls nor the pregnant women had BCM levels greater than 25 U/ml. In contrast, 87 of 115 patients (75%) with metastatic breast cancer had BCM levels greater than 25 U/ml. All control persons had CA 15-3 levels less than 25 U/ml, but 2 out of 9 pregnant women (22%) had levels greater than 25 U/ml. Seventy-four out of 97 patients (76%) with metastatic breast cancer had CA 15-3 levels greater than 25 U/ml. A statistically significant correlation was found between BCM and CA 15-3 in the breast cancer patient group (r = 0.883, p less than 0.001, n = 134) and in the normal control group (r = 0.743, p less than 0.001, n = 30). BCM and CA 15.3 both showed no correlation with CEA in breast cancer patients (r = 0.060, n = 81; and r = 0.146, n = 78, respectively). BCM had a range of sensitivity similar to that of the CA 15-3 RIA. Our results suggest that BCM may be a useful new marker for monitoring the clinical course of patients with breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2096995 TI - Axillary versus peripheral blood levels of sialic acid, ferritin, and CEA in patients with breast cancer. AB - Serum levels of total sialic acid, carcinoembryonic antigen (CEA), ferritin, lactate dehydrogenase, and creatine phosphokinase were measured both in tumor drainage blood (axillary vein) and in peripheral blood obtained from 121 breast cancer patients during surgery. No significant differences between mean values in peripheral and tumor draining blood, between cancer patients and healthy controls, or between patients with or without axillary lymph node metastases were found for any of the markers. Both ferritin and CEA levels were higher in axillary and peripheral blood from patients with central breast cancer versus other sites but the difference was significant only for CEA (p less than 0.05). CEA levels were significantly higher (p less than 0.01) in patients with greater than 2 cm diameter carcinomas versus T1 stage patients in axillary but not in peripheral blood. When the cephalic vein was clamped before the axillary sample was taken, ferritin showed a significant increase (p less than 0.05). We conclude that measurement of sialic acid, CEA, and ferritin in axillary venous blood in breast cancer patients is not of clinical benefit, although further data are needed to clarify whether other advantages can be derived. PMID- 2096997 TI - Comparison of ligand binding assay and enzyme immunoassay of oestrogen receptor in human breast cancer cytosols. Experience of the E.O.R.T.C. Receptor Group. AB - Nine laboratories cooperating in the Receptor Study Group of the EORTC compared results of ligand binding assay supplemented with Scatchard plot analysis (LBA) and enzyme immunoassay (EIA) for the assessment of oestrogen receptors in 1665 breast cancer cytosols. An excellent agreement was observed between results of Scatchard plot analysis and EIA in each laboratory. Linear correlation coefficients of log-transformed data (log [(ER + 10)/10]) ranged from 0.839 to 0.977 (n = 52-373; P less than 0.001); Spearman's R ranged from 0.797 to 0.972 (P less than 0.001). Orthogonal regression analysis on log-transformed data revealed slopes of 0.794 to 1.141 and intercepts of -0.057 to 0.154 corresponding to -1.2 to 4.3 fmole/mg protein. Both assays compared equally well for pre- as well as postmenopausal patients, which confirms that occupied receptors are not extracted during the preparation of cytosol. The percentage discordance in the classification of tumours as ER positive or negative varied from 4.1 to 13.3 when a cut-off value of 10 fmol/mg protein was used, and from 1.4 to 7.5 at a cut-off level of 20. Considerable variations were observed in the actual receptor levels reported by each laboratory. Since these differences occurred in the results of both methods, they are attributed to differences in tissue handling. It is concluded that the ER-EIA is an excellent alternative to Scatchard plot analysis for the assay of oestrogen receptors. It is recommended, however, that laboratories performing assays on samples obtained from patients who are eligible for entrance in EORTC clinical trials and who wish to use the EIA should validate this assay against the Scatchard plot assay in their own setting. PMID- 2096996 TI - Epidermal growth factor receptors and prognosis in primary breast cancer. AB - A retrospective study was performed on 109 human breast tumors stored in liquid nitrogen in order to assess the prognostic value of epidermal growth factor receptor (EGF-R) (median patient follow-up 5 years). A significant inverse relationship was observed between EGF-R and both estrogen (ER) and progesterone receptors (PR). Univariate analysis showed a trend towards a shorter metastasis free survival both in the overall population and in node-negative patients with EGF-R positive tumors. Multivariate analysis of the overall population showed that lymph-node involvement and PR status were the only significant variables in predicting metastasis-free survival. However, in patients receiving no adjuvant treatment (hormone therapy or chemotherapy). EGF was the only significant variable in the multivariate Cox analysis. No c-erbB-1 amplification was detected in these tumors. PMID- 2096998 TI - Protein tyrosine kinases in human breast cancer: kinetic properties and evidence for the presence of two forms of native enzyme. AB - The protein tyrosine kinase (PTK) of human breast tumors classified as positive (TM+) or negative (TM-) according to their estrogen and progestin receptor levels was partially characterized with regard to its distribution, kinetic parameters, molecular size, and ability to phosphorylate endogenous mammary proteins. For both types of tumors, PTK activity depended upon the presence of Mn++ (2-5 mM) and/or Mg++ (10-20 mM). The activities, total (per g of tissue) and specific (per mg of protein), were similar for both types of tumors, and an average of 60% of activity was located in cytosolic fractions. The autoradiographic detection of alkali-resistant phosphoproteins after SDS-PAGE showed very similar patterns between corresponding fractions from both types of tumors. Upon gel filtration, two peaks of activity of apparent Mr 245 kDa (peak I) and 47 kDa (peak II) were observed. Peak II was found in both cytosols and extracts from particulate fractions, while peak I was present only in the latter fraction for both TM+ and TM- tumors. The apparent Km's for ATP ranged from 4.1 to 6.6 microM, and from 11 to 34 micrograms/ml for the synthetic substrate poly [Glu80, Tyr20], at an optimal pH of 6.5-7.5. When endogenous alkali-resistant phosphorylation of peaks I and II was determined by autoradiography after SDS-PAGE, two major mammary proteins of Mr 60 and 45 kDa were phosphorylated by peak II and three, Mr 145, 74, and 62 kDa, by peak I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097000 TI - Effects of cold shock treatment on amphibian oocytes: alteration of heterogenous nuclear RNP morphology. AB - In cold-stressed oocytes of Pleurodeles waltl, lampbrush chromosome lateral loops exhibited important structural modifications which were visualized under light microscopy. Electron microscopy study revealed that the RNP particles associated with growing transcripts in the matrix of these loops were 15 nm at 8 degrees C compared to 30 nm at normal temperature (20 degrees C); hnRNP isolated from cold stressed oocytes sedimented at 15 S in sucrose, while those from control oocytes sedimented at 30 S, as expected. However, under both normal and cold stress conditions, hnRNP possessed a buoyant density of 1.38 g/cm3 in CsCl, indicating that their typical RNA/protein ratio was maintained at 8 degrees C. Our results demonstrate that cold stress affects the structure of hnRNP in amphibian oocytes. PMID- 2096999 TI - Confocal microscopy as a tool to reveal the tridimensional organization of intracellular lumens and intercellular cysts in a human colon adenocarcinoma cell line. AB - Adenocarcinoma cells often form intracellular lumens and intercellular cysts. In order to study the structural relationships between these lumens and the apical domain of normal enterocytes, we have applied electron microscopy and confocal microscopy to a cloned cell line derived from the human colon adenocarcinoma cell line LoVo which express a high number of intracellular lumens and intercellular cysts. Microvilli reminiscent of those detected in the brush border of small intestinal cells are formed in the two types of compartments. By immunofluorescence, we found that a 135 kDa membrane glycoprotein characterized by a monoclonal Ab and normally associated with the brush-border of enterocytes is expressed at the surface of the intracellular lumens and intercellular cysts present in the adenocarcinoma cells. Comparison of fluorescence and reflection contrast micrographs obtained by confocal microscopy demonstrate the presence of spherical intracellular lumens in the juxtanuclear region of single cells, and of more complex shaped intercellular cysts located within clusters of cells. The later cells form junctional complexes limiting an apical plasma membrane domain in contact with the intercellular cyst. It is suggested that the intracellular lumens may represent the abortive form of an apical plasma membrane due to the lack of components required to establish epithelial cell contacts. As opposed to conventional fluorescence microscopy, confocal microscopy allows rapid inspection of the tridimensional organization of intracellular lumens and intercellular cysts even when they are located in cell multilayers. PMID- 2097001 TI - High levels of HMG1-2 protein expression in the cytoplasm and nucleus of hydrocortisone sensitive amphibian thymocytes. AB - A major 26 kDa protein was identified in the cytoplasmic and nuclear compartments of axolotl thymocytes. A polyclonal antiserum was produced against the denatured form of this protein. High levels of 26 kDa were expressed by hydrocortisone sensitive lymphocytes which represent a major thymocyte subpopulation in young animals. However, no further expression of the 26 kDa protein was observed in involuted thymus of adult animals nor in thymus of young artificially metamorphosed axolotls. The 26 kDa was never expressed by splenic and blood peripheral lymphocytes at any stage of development. Partial N-terminal amino acid sequence and amino acid composition demonstrate that the 26 kDa polypeptide is strongly homologous to HMG1-2 proteins, the most abundant members of the high mobility group (HMG) non-histone chromosomal proteins. HMG1-2 are thought to be involved in the organization of chromatin structure, as well as in the stability, replication and transcription of DNA. It was confirmed that the 26 kDa axolotl polypeptide is recognized by a well characterized rabbit antiserum to rat HMG1-2 proteins. PMID- 2097002 TI - Quantitative immunocytochemical studies of endogenous albumin in rat aortic endothelial and mesothelial cells. AB - Endogenous albumin was revealed over cellular structures of rat ascendent aorta endothelia and mesothelium, with high resolution and specificity, by applying the protein A-gold immunocytochemical approach. This approach allows albumin distribution to be studied under steady-state conditions. The cellular layers evaluated were the aortic endothelium, the capillary endothelium (vasa vasorum), and the mesothelium externally lining the aorta at this level. Gold particles, revealing albumin antigenic sites, were preferentially located over plasmalemmal vesicles and intercellular clefts of endothelial and mesothelial cells, though with different labeling intensities. The interstitial space was also labeled. Morphometrical evaluation of plasmalemmal vesicles demonstrated a higher surface density for these structures in capillary endothelial cells (12%) compared with those in aortic endothelial (5%) and mesothelial cells (2%). Quantitation of gold labeling intensities over these structures revealed a higher labeling over plasmalemmal vesicles of capillary endothelium than over those of aortic endothelium and mesothelium. This result, together with the higher surface density of plasmalemmal vesicles found in capillary endothelium, suggest an important role of these structures in the transendothelial passage of endogenous albumin, particularly for capillary endothelium. On the other hand, labeling densities over mesothelial clefts were found to be higher than those of capillary and aortic endothelia. Results from this study concur with the proposal of a differential passage of albumin according to the cell lining considered, and suggest to a role for mesothelial intercellular clefts in contributing to the presence of albumin in interstitial spaces. PMID- 2097003 TI - Relationship between vitamin D status and deposition of bound calcium in skeletal muscle of the rat. AB - The effects of vitamin D on the intramuscular distribution of total and bound calcium, phosphate and on available cytosolic calcium, were investigated in skeletal muscle. Total calcium and phosphorus were measured on ashed subcellular fractions of muscles from vitamin D-repleted and vitamin D-deprived rats. The variations in available calcium were followed by determining the activities of calcium-sensitive enzymes in isolated cytosol. Bound-calcium was revealed ultra microscopically by pyroantimonate. In vitamin D-repleted muscles, the pyroantimonate method revealed specific areas of intense bound-calcium deposition: the myofibrils, where they formed pronounced lines parallel to the Z bands. In vitamin D-deficient muscles, the calcium-pyroantimonate deposits appeared clearly reduced. This loss was accompanied by a marked reduction in total calcium and phosphorus in all the subcellular fractions, as compared to vitamin D-repleted muscles. Unexpectedly, the activity of the Ca(+)-activated isocitrate-dehydrogenase was increased in the cytosol, while that of the Ca2(+) inhibited pyruvate-kinase decreased. Prolonged vitamin D-administration to vitamin D-repleted rats led to an intensification of calcium-pyroantimonate deposits and a general increase in total calcium and phosphorus, but no change in the cytosolic Ca2(+)-sensitive enzyme activities. Cessation of vitamin D administration to vitamin D-repleted rats produced a regression of calcium pyroantimonate deposits, a general decrease of total calcium and phosphate levels, and stimulation of the Ca2(+)-activated isocitrate-dehydrogenase accompanied by lowering of the Ca2(+)-inhibited pyruvate-kinase. The results clearly indicate a correlation between vitamin D-repletion and the total and bound calcium content of skeletal muscle. In addition, they demonstrate an apparent contradiction between the decrease of total and bound calcium, and the activities of cytosolic Ca2+ sensitive enzymes during vitamin D-deprivation, which can only be explained by an increase in available calcium. It is suggested that vitamin D stimulates intramuscular mechanisms tending to lower available calcium by inactivating the cation via the formation of calcium chelates. PMID- 2097005 TI - How best to analyse new strategies in bone marrow transplantation. PMID- 2097004 TI - The stroma-vascular fraction of rat inguinal and epididymal adipose tissue and the adipoconversion of fat cell precursors in primary culture. AB - The stroma-vascular fraction (SVF) of inguinal and epididymal fat pads of 4 week old rats was studied by electron microscopy. Among the various cell types, endothelial cells and preadipocytes were found in both SVF, while mesothelial cells were only detected in the epididymal SVF. The resulting heterogeneity of primary culture and the adipoconversion of the fat cell precursors were studied in a serum-supplemented medium enriched with insulin (14.5 nM) and exogenous triglycerides. Despite the heterogeneity of the inoculum, the primary cultures were rather homogeneous, fat cell precursors being the main cell type. Distinctive contaminant fibroblast-like cells were observed in both cultures, whereas epithelial-like cells, which correspond most probably to mesothelial cells, were only found in epididymal cultures. Differentiation of fat cell precursors was assessed by the appearance of lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPDH). LPL activity was found in the same level in cells of both deposits while GPDH activity was elevated in inguinal vs epididymal derived stroma-vascular cells. The different adipose conversion pattern of both cultures was confirmed by morphological quantification: the maturation of epididymal fat cell precursors was faster but less extensive. These differences could be related mainly to regional localization rather than to different maturation of the two fat deposits. PMID- 2097006 TI - Neutrophils are responsible for the reappearance of chemiluminescence after allogeneic bone marrow transplantation. AB - The nature of the cells generating the early chemiluminescence (CL) response after allogeneic bone marrow transplantation (BMT) was studied in six patients; five transplanted for acute leukaemia and one for multiple myeloma. Peripheral blood was fractionated into 14 fractions with Percoll narrow range density gradient centrifugation on days +14, +17, +20, and +27 after BMT. The leucocytes were recovered in fractions 7-14 which were analysed for cell morphology and CL response. On days +14 to +20 after BMT the CL response was detected in the fractions containing morphologically mature neutrophils. In one of these fractions the CL response per phagocyte was significantly higher than in the neighbouring fractions although morphologically the cells were similar. The results suggest that the cells responsible for the early CL after BMT are neutrophils and possibly an active subpopulation of neutrophils produced by the marrow graft. PMID- 2097007 TI - T cell depletion of human bone marrow using an oxidase-peroxidase enzyme immunotoxin. AB - We have shown in a previous paper that an antibody-enzyme immunotoxin (eIT) constructed by chemically coupling the 097 monoclonal antibody to glucose oxidase and to lactoperoxidase (097 eIT) effectively eliminated T cells of human peripheral blood origin and killed cultured human thymoma cells. Here we tested its effectiveness against T cells present in human bone marrow cell suspensions contaminated by large numbers of erythrocytes. The T cell-depleting capacity of the 097 eIT was assessed by means of four different assay methods, three of which gave concordant results and indicated an effective depletion comparable in efficiency to published work. For example, by limiting dilution analysis assay of IL-2-producing T cells we found approximately 3 logs of T cell depletion. The growth of bone marrow stem cells (CFU-GM, CFU-E and BFU-E) was not affected by treatment with the 097 conjugates. PMID- 2097008 TI - Use of the polymerase chain reaction to monitor engraftment following allogeneic bone marrow transplantation. AB - Engraftment following allogeneic bone marrow transplantation (BMT) was assessed in three cases, two of which were sex-mismatched and one sex-matched. The polymerase chain reaction (PCR) was used to amplify the hypervariable region lying 3' to the apolipoprotein B gene on chromosome 2. Amplification of this region provided informative marker bands capable of distinguishing host/donor populations in each case. The method allowed rapid analysis of minimal numbers of cells from peripheral blood and bone marrow in the early stages following BMT and was predictive of either successful engraftment or graft failure. PMID- 2097009 TI - Ophthalmological and other toxicities related to cytosine arabinoside and total body irradiation as preparative regimen for bone marrow transplantation. AB - Cytosine arabinoside, 3 g/m2, every 12 h for 6 days, followed by fractionated total body irradiation, 200 cGy twice daily for 3 days, was administered to 39 adult patients undergoing bone marrow transplantation. Allogeneic transplant patients received cyclosporin and methotrexate for prophylaxis of graft-versus host disease. There were 21 autologous transplants (16 with acute leukemia, four with an advanced stage of chronic myelocytic leukemia, and one with lymphoma) and 18 allogeneic transplants (14 with acute leukemia, two with an advanced stage of chronic myelocytic leukemia and two with myelodysplastic syndrome). Toxicities were compared between the two groups. There was a significantly greater degree and duration of mucositis and a greater frequency of radiation-type retinopathy developing in the allogeneic group, predominantly in those having had radiation for prophylaxis or treatment of central nervous system leukemia. Seven of 11 acute leukemic patients who received autologous transplants in remission survive. Two of seven acute leukemias who received allogeneic transplants while in remission survive. Although the increased morbidity, retinitis and mucositis, observed in the allogeneic group indicates that this regimen when combined with methotrexate and cyclosporin is too toxic, the results in autologous transplantation in acute leukemia in remission are encouraging. PMID- 2097010 TI - Psychological distress in parents consenting to child's bone marrow transplantation. AB - The purpose of this study was to determine the nature and prevalence of the psychological symptomatology in parents of children undergoing bone marrow transplantation (BMT) and to investigate the manner in which certain psychosocial factors are related to parental distress associated with the informed consent process. A total of 61 parents (46 mothers and 15 fathers) were assessed with respect to psychological distress, coping styles, quality of physician-patient communication, and recall of BMT information after providing written consent for their child to have BMT. Forty-seven percent of fathers and 60% of mothers exhibited significant psychological distress of a generalized nature. Mothers exhibited a broader range of specific psychological symptomatology and more severe levels of depression and phobic anxiety than did fathers. The level of parents' distress was unrelated to characteristics of their child's disease or treatment milieu, or to parents' recall of BMT information. However, emotional coping was positively related to psychological distress whereas the quality of the communication between physician and parent was inversely related. The findings from this study suggest that approximately 50% of all parents could benefit from psychological interventions which promote the efficient utilization of coping strategies and highlight the importance of the nature of the communication style used by oncologist-investigators in obtaining informed consent. PMID- 2097011 TI - In vitro comparison of two methods of T cell depletion associated with different rates of graft failure after allogeneic marrow transplantation. AB - Clinical trials in another center have shown a substantially lower risk of graft failure associated with T cell depletion by treatment of donor marrow with the use of an antibody against CD6 compared to depletion with a mixture of eight antibodies previously used for clinical trials in our center. In order to evaluate mechanisms possibly responsible for this difference, we compared lymphoid cell surface phenotypes and in vitro functions in marrow cells treated by complement-mediated lysis with anti-T12 (CD6) or with the eight antibody mixture. Treatment with the eight antibody mixture produced more than three log depletion of precursors for IL-2-producing cells (pIL-2) and approximately one log depletion of precursors for NK cells. On the other hand, treatment with anti T12 produced approximately one log depletion of pIL-2 and had no effect on NK precursors. Additional studies were carried out with treated marrow cells cultured in medium containing recombinant IL-2. Compared to cells treated with the eight antibody mixture, the marrow cells that remained after anti-T12 treatment had more cytotoxic activity against K562, Daudi and an EBV-transformed human B cell line during the first 6 days of culture, but marrows treated by the two methods showed similar cytotoxic activity after 10 days of culture. Cultures from marrow treated with anti-T12 contained more CD3+ and CD6+ cells than cultures from marrow treated with the eight antibody mixture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097012 TI - Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purged marrows for children with acute non-lymphoblastic leukemia in second remission. AB - Although autologous bone marrow transplantation (ABMT) following purging with 4 hydroperoxycyclophosphamide (4HC) has been effective for some adults with acute non-lymphoblastic leukemia (ANLL), there are few data on ABMT for children. We have performed ABMT for 13 patients (median age, 5 years) with ANLL in second remission. Bone marrow was treated ex vivo with 4HC to kill residual leukemic cells. In order to enhance the anti-leukemic effect of 4HC, exogenous red blood cells were eliminated from the marrow/4HC mixture. All patients were conditioned for transplantation with busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg), followed by infusion of the 4HC treated marrow. Eleven of 13 patients had complete hematologic reconstitution; there were no transplant-related deaths. Five patients relapsed at 2, 4, 5, 6 and 6 months post-BMT. Eight patients are disease-free survivors; the median time for survival is 24 months, with a projected disease-free survival of 61%. ABMT is a safe and efficacious treatment modality for children with ANLL in second remission. Our results suggest that the disease-free survival for pediatric patients may be superior to that seen in adults. PMID- 2097014 TI - Anesthetic management of marrow harvesting from a 7-week-old premature baby. AB - Bone marrow was harvested from a 3.95 kg premature 7-week-old female baby for donation to a 13 kg HLA-identical sister with severe aplastic anemia. Two hundred ml of donor bone marrow were aspirated, containing a calculated dose of 3 x 10(8)/kg nucleated bone marrow cells for the recipient. This was equivalent to two-thirds of the donor's calculated blood volume (320 ml). Peri-operative care included invasive monitoring of intravascular pressures, arterial blood gas analysis, careful temperature control and the infusion of 150 ml of packed red cells, 150 ml of colloid and 50 ml of crystalloid. Rapid engraftment occurred. There were no complications and both donor and recipient are healthy 12 months later. PMID- 2097013 TI - Informed consent for bone marrow transplantation: identification of relevant information by referring physicians. AB - Two hundred Michigan hematologists-oncologists were sent a 34-item questionnaire designed to assess what patients should know at the time of giving consent to bone marrow transplant (BMT). Sixty-three (32%) responded to a single mailing and rated items on a 8-point scale, varying from 0 = no need to know to 7 = appreciation of consequences essential. The mean rating across items was 5.2, indicating that all items were important. Statistically, the items separated into three groups: (1) above average importance - 13 items; (2) average importance - 9 items; (3) below average importance - 12 items. Items of above average importance included the rationale for BMT and the collective risks and benefits of the process, including the patient's well-being post-transplant. Informed consent documents did not include 5/13 items of above average importance, yet 12/21 items of average and below average importance were included. Fourteen demographic variables were correlated with each item and none were significant, indicating that the ratings represent a broad consensus in the referring physician community as to what a patient should understand before consenting to BMT. The vast majority of referring physicians agreed that patients usually have an adequate understanding of BMT at the time of giving informed consent and that a fully informed patient is more likely to adhere to the treatment regimen. PMID- 2097015 TI - Acute megakaryoblastic leukemia with massive myelofibrosis: complete remission and reversal of marrow fibrosis with allogeneic bone marrow transplantation as the only treatment. AB - We report results of allogeneic bone marrow transplantation in an 8-year-old boy with acute megakaryoblastic leukemia characterized by intense fibrosis together with 20% blast cells in the bone marrow, who was transplanted without preceding chemotherapy for remission induction. Conditioning comprised cytosine arabinoside, cyclophosphamide and total body irradiation. The donor was his HLA identical sister. The patient is well with minor chronic graft-versus-host disease and normal hematologic values 670 days post-transplant. PMID- 2097016 TI - Interferon induced cytogenetic improvement in CGL patients in haematological relapse post allograft. PMID- 2097017 TI - Microwave diathermy. PMID- 2097018 TI - Overtraining syndrome. AB - This review discusses the overtraining syndrome which is characterized by fatigue and underperformance precipitated by stress of training. Other stresses, depression and an increased susceptibility to infections may be important. Treatment requires rest and a stress management program over 3 months. PMID- 2097019 TI - Intensive training in young athletes. AB - An increasing number of children take part in organized sporting activities, undergoing intensive training and high level competition from an early age. Although intensive training in children may foster health benefits, many are injured as a result of training, often quite seriously. This paper reviews some of the areas of research dealing with intensively trained young athletes, and focuses on physical, cardiovascular and muscular effects, sports injuries and psychological effects of intensive training. It is concluded that measures should be taken to modify present training and competition schemes to avoid the deleterious effects of intensive physical activity on these children. PMID- 2097020 TI - Cost of a roller skating rink to the local accident and emergency department. AB - A 14 month retrospective study was undertaken to determine the cost implications of the opening of a roller skating rink to the local hospital accident and emergency department (A and E). A total of 398 patients attended following injury at the roller skating rink, of whom 384 were included in the study. The estimated cost of their injuries was determined by the hospital accounts department. The average cost per patient attending the A and E department following roller skating injury was about 100 pounds. The total cost to the A and E department of all injuries sustained at the rink over this period was 38,412 pounds. The cost implications of opening a roller skating rink for the A and E department are considerable. If proposals for self-budgeting are applied, A and E departments will have to seek additional funding if such leisure facilities are opened in their vicinity. PMID- 2097021 TI - Sacral stress fracture in a runner. PMID- 2097022 TI - Ulnar nerve compression in the cyclist's hand: two case reports and review of the literature. PMID- 2097023 TI - Stress fracture of the sixth rib in a canoeist. PMID- 2097024 TI - Rest in underperforming elite competitors. AB - This study examines the effects of 3-5 weeks of physical rest on selected physical, physiological and psychological parameters obtained from 12 Olympic but latterly underperforming competitors and their matched control subjects. Cardiorespiratory data were directly determined from their work to volitional exhaustion on either a treadmill, cycle, or rowing ergometer. Anaerobic power and capacity were evaluated through modified Wingate tests. For psychometric assessments, the Profile of Mood States (POMS) was used. For the Olympic competitors, one-way analyses of variance (ANOVA) revealed significant increases (p less than 0.05) in body weight, maximum respiratory exchange ratio, maximum oxygen consumption, and heart rate at the anaerobic threshold, following the rest period. There was also a significant reduction in fatigue and mood profile score, and a significant increase in vigour. No significant changes were found in the matched control subjects. The present data show that resting for 3-5 weeks assists underperforming elite competitors to improve their aerobic performance. PMID- 2097026 TI - Amateur soccer: injuries in relation to field position. PMID- 2097025 TI - Criteria to indicate testosterone administration. AB - A detection method for testosterone administration was developed using radioimmunoassay to measure the urinary ratios of testosterone (T) to epitestosterone (E) and to luteinizing hormone (LH). A comparative study of the effect on these ratios of a single intramuscular injection of testosterone heptanoate followed by stimulation with human chorionic gonadotrophin (HCG) in three normal men was undertaken. To allow immediate investigation, a commercially supplied epitestosterone antiserum was used. This study showed that both T/E and T/LH ratios could be used to detect testosterone administration, the latter also being an indicator of HCG use due to cross-reactivity with the LH antiserum. Subsequently, an epitestosterone antiserum of superior specificity was raised and used in a study to demonstrate the insignificant effect of exercise on these ratios. Finally, an intramuscular injection of a combined preparation of testosterone/epitestosterone heptanoates resulted in raised ratios of T/LH but not of T/E. This demonstrated the importance of the T/LH ratio in circumstances where the T/E ratio can be easily circumvented. PMID- 2097027 TI - Gastrointestinal disturbances in marathon runners. AB - To determine the prevalence of various gastrointestinal disturbances related to long-distance running and its effect on weight, diet and everyday digestive problems, we gave a questionnaire to 279 leisure-time marathon runners, comprising 10% of the participants in a local marathon race. Their answers disclosed a prevalence of dietary changes, weight reduction and altered bowel habits (mainly looser stools and/or more frequent defaecation) of 37, 38 and 48% respectively. A quarter reported earlier long lasting gastrointestinal problems, which improved in 41% of the runners after they started regular training. Thirty four percent experienced gastrointestinal disturbances during or after running, 20% to such an extent that it seriously affected their performance. PMID- 2097029 TI - Effects of setting eggs small end up on hatchability and posthatching performance of broilers. AB - 1. Hatchability of fertile eggs incubated with their small ends up (SEU) was 16 to 27% lower than for eggs set with their large ends up (LEU). In addition, the SEU position produced more nonviable chicks. 2. There were no differences in post hatching performance between the two incubation treatments. 3. A survey in a commercial hatchery revealed that the frequencies of eggs set upside down by mistake varied from 0.3% to 3.4%. The setting of eggs upside down was attributed not to difficulties in distinguishing the large and small ends of the eggs but to human error. A decrease in the number of Grade-A chicks of about 0.2% was observed for every 1% of eggs set upside down, suggesting it may be of economic importance to ensure that the eggs are set properly with their large ends up. PMID- 2097028 TI - Injuries at the BMX Cycling European Championship, 1989. AB - At the BMX Cycling European Championship in 1989 with 976 participants of both sexes, aged between six and 40 years, all injuries were registered. A total of 6.3% of the participants sustained injuries (1.6% per individual start), 52.5% required medical attendance and 3.3% necessitated hospital admission. Women were injured twice as frequently as men. Most injuries, 72.1%, were minor, 6.6% were fractures with 75% of the fractures affecting the upper limbs. BMX bicycle riding has the high injury risk of 1190 injuries per 1000 competition hours. PMID- 2097030 TI - Potential of chemical regulation of food intake and body weight of broiler breeder chicks. AB - 1. Two experiments were performed to evaluate the potential of phenylpropanolamine hydrochloride and monensin sodium as appetite- and weight control agents for Indian River broiler breeder chicks. 2. In experiment 1, a total of 300 day-old sexed broiler breeder chicks were individually weighed and placed in battery cages. They were randomly assigned to 5 dietary treatments, namely 0, 50, 100, 200 and 400 mg/kg of phenylpropanolamine hydrochloride added to a maize-soyabean meal basal diet. 3. In experiment 2, a total of 400 day-old sexed broiler breeder chicks were randomly assigned to 10 dietary treatments which were a combination of two concentrations of dietary crude protein (200 and 150 g/kg) and 5 different concentrations of added drugs in the diet, namely 0, 500 and 800 mg/kg of phenylpropanolamine hydrochloride and 200 and 300 mg/kg of monensin sodium. 4. Food consumption and body weight gain were significantly reduced by feeding diets containing the drugs but mortality was not significantly affected. Birds showed evidence of increased tolerance, with age, to phenylpropanolamine but not to monensin. 5. Monensin sodium, at high inclusion rates, was found to be a more potent and effective appetite- and growth depressing agent for broiler breeder chicks than phenylpropanolamine and may have application in broiler breeder production using an ad libitum feeding programme. PMID- 2097031 TI - The relationships between dietary crude protein, body weight, and fertility in naturally mated broiler breeder males. AB - 1. Naturally mated male broiler breeders were fed to achieve five levels of body weight gain on a high (160 g crude protein (CP)/kg) or low (110 g CP/kg) protein diet. Males were separately fed in 9 of the experimental treatments and fed with the females in the other. 2. There was an optimum body weight for maximum fertility which changed with age. The best fertility was shown by males weighing 3.2 kg at 26 weeks rising to 4.0 kg at 60 weeks of age. 3. The low protein diet was associated with higher fertility, particularly during the latter part of the breeding period (49-60 weeks). 4. Head width reached a plateau after 26 weeks of age and was 1 mm greater in males weighing more than 5 kg compared with males weighing 3 to 4 kg at 60 weeks of age. PMID- 2097032 TI - Reassessment of riboflavin requirement for single comb White Leghorn pullets from 0 to 6 weeks of age fed on maize-soyabean meal diets and its subsequent effect on sexual maturity and egg production. AB - 1. Two experiments were conducted using a total of 228 Hyline W-26 1-d-old pullets in each experiment. The purpose of the study was to reassess the riboflavin requirement from 0 to 6 weeks of age (WOA) and its subsequent effect on sexual maturity and egg production using a maize-soybean meal diet. 2. Approximately 10% incidence of curly toe paralysis was observed among birds fed on the diet with no added riboflavin (1.5 mg total riboflavin/kg diet). 3. Applying the non-linear regression model to the body weight gain data at 3 and 6 WOA in both the experiments, it was found that the minimum total riboflavin required to achieve maximum body weight gain for the two age periods was 2.3 and 2.0 mg/kg of the total diet. This is equivalent to 5.0 and 5.7 micrograms riboflavin/g of body weight gain from 0 to 3 and 3 to 6 WOA respectively. 4. Birds fed on the diet containing no added (1.5 mg total/kg) riboflavin laid fewer eggs and had lower body weights at 24 weeks. 5. We conclude that, from 0 to 6 WOA, at least 2.3 mg total riboflavin/kg should be present in the diet to prevent curly toe paralysis, obtain the maximum body weight gain and sustain the subsequent performance at sexual maturity. PMID- 2097033 TI - Effect of feeding technique, ad libitum, dry or wet force feeding, on the metabolisable energy values of raw materials for poultry. AB - 1. Metabolisable energy values (AME, AMEn, TME and TMEn) of three raw materials (maize, sunflower meal and soyabean meal) were determined in adult cockerels using two classical feeding e techniques (ad libitum and force-feeding of dry food) and a new one in which birds were force-fed wet diets. 2. In the wet force feeding assay nitrogen balances and food intakes were similar to those achieved with ad libitum feeding. The duration of the assay using wet force-feeding was only 2 d as compared to the 3 or 7 d experimental periods for the dry or the ad libitum assays respectively. 3. TMEn values were not dependent on the feeding technique used; AME and AMEn data obtained in the ad libitum and wet force feeding assays were close to TMEn values. As expected, these values were underestimated in the dry force-feeding assay. PMID- 2097034 TI - Protein requirement of fast- and slow-growing chicks. AB - 1. Responses of male broiler chicks and male chicks of an egg-laying stock to dietary crude protein (CP) concentrations ranging from 167 to 251 g/kg (metabolisable energy content 13 MJ/kg) were compared from 0 to 21 d of age, using 20 groups of 9 or 10 chicks (5 diets x 2 stocks x 2 replicates). 2. Average growth rate in the broilers was three times that of the layer chicks. The broilers needed at least 251 g CP/kg to maximise their liveweight gain but the layer chicks needed only about 188 g CP/kg. 3. The broiler chicks ate less than twice as much food as the layers and their maximum gain/food ratio was 0.6 compared with 0.4 for the layer chicks. These maximum efficiencies of conversion of food to liveweight were achieved in both cases with a diet containing 230 g CP/kg. 4. The efficiency of protein utilisation (above maintenance) was the same in fast- and slow-growing genotypes (about 0.47 g protein gain/g protein consumed). 5. Carcase analysis at 3 weeks of age showed that the broilers had deposited more fat than the layers and that protein content of the diet had markedly influenced fat deposition in both stocks. Fat in the whole body increased from 29 to 87 g/kg in the layer chicks and from 81 to 123 g/kg in the broilers as dietary protein was reduced from 251 to 167 g/kg. 6. The optimum protein to energy ratio of a chick starter diet will depend on the growth potential of the stock, as well as the cost of ingredients and the value of fatter or leaner carcases. PMID- 2097035 TI - Anti-nutritive activity of wheat pentosans in broiler diets. AB - 1. To assess their possible anti-nutritive activity wheat pentosans were isolated from a milling by-product and added at graded levels to a sorghum-based broiler chicken diet. 2. A water-insoluble pentosan preparation (WIP, 720 g arabinoxylan/kg) caused a depression of apparent metabolisable energy (AME) of 1.63 MJ/kg DM at the highest level of inclusion (41.9 g/kg). Broilers maintained on this diet showed significant growth depression and a decrease in feed conversion efficiency. 3. A water-soluble pentosan preparation (WSP, 520 g arabinoxylan/kg) showed less anti-nutritive activity. 4. In a second experiment the AME of rice (pearled), maize, sorghum, wheat, triticale, barley and rye was determined. The AME values obtained were highly correlated (r = -0.98, P less than 0.001) with the summed levels of pentosans and beta-glucans found in the cereals. 5. It was concluded that the pentosans of wheat possess anti-nutritive activity when present in broiler diets and that similar polysaccharides may influence the nutritive value of other cereals. PMID- 2097036 TI - Effects of blood sampling on plasma concentrations of corticosterone and glucose in laying hens caged in groups. AB - 1. The effects of taking a blood sample from one bird in a caged group on plasma concentrations of corticosterone and glucose in birds from its own group and birds from other groups were investigated. 2. Two blood sampling protocols were used: successive (all birds within a group were sampled one immediately after another) and alternative (birds from different groups were sampled one after another until all birds in all groups had been sampled). 3. Neither sampling protocol nor between or within group sampling rank was related to plasma concentrations of corticosterone and glucose. 4. The time taken to remove a blood sample (generally more than 45 s but less than 2 min) did not influence circulating corticosterone and glucose. 5. In individual birds plasma concentrations of corticosterone and glucose were poorly correlated with one another. 6. It is concluded that it is possible to take blood samples from a bird, kept in a group, without affecting plasma concentrations of corticosterone and glucose in other birds from that group or in birds from other groups in other cages. PMID- 2097037 TI - Changes in the plasma concentrations of prolactin, luteinising hormone, progesterone and D-(beta)-hydroxybutyrate in turkey hens (Meleagris gallopavo), during treatment of broodiness under commercial conditions. AB - 1. An experiment was done under commercial conditions to investigate the physiological effects of isolating broody turkey hens, for 72 h, in sand and wire floored pens on the third, 10th and 16th weeks of production. 2. Hens identified as broody and removed from the flock had higher plasma prolactin concentrations than the laying hens at each of the three experimental stages. 3. Confinement in sand and wire floored pens, induced a decline in plasma prolactin concentrations. This decline probably impeded immediate development of broody behaviour. Alternately, levels of prolactin higher than those of laying hens were again measured 7 and 14 days after treatment during third week but not after the 10th and 16th week of production. 4. Confinement did not induce consistent changes in luteinising hormone (LH) and progesterone concentrations from one period to an other. 5. An increase in the plasma concentration of D-(beta)-hydroxybutyrate was observed in the hens which had an egg present in the oviduct on day 2, 3 and/or 4 of the treatment. Subsequently, a decrease in ovulation rate was observed in the hens with higher concentrations of D-(beta)-hydroxybutyrate while under treatment, during the 10th week of production. 6. These data confirm that the effectiveness of the traditional methods for broodiness prevention under commercial conditions is related to the induction of a decrease of prolactin. PMID- 2097038 TI - Effects of sex and gonadal steroids on arginine vasotocin and mesotocin in the pineal gland and neurohypophysis of White Leghorn fowls. AB - 1. Pineal and neurohypophysial arginine vasotocin (AVT) and mesotocin (MT) were measured in White Leghorn hens, cockerels and castrated males treated with either testosterone propionate (TP) or oestradiol benzoate (EB) (n = 10/group). The lighting regimen was 14 h light: 10 h dark, supplied by natural diffused sunlight and incandescent bulbs. 2. Both AVT and MT were detected in the pineal gland of all the chickens. 3. There was no significant effect of either sex or treatments on pineal MT. 4. Females had about 4 times more pineal AVT than males, regardless of their treatment. There was no effect of the treatments on pineal AVT in the males. 5. No sexual difference in neurohypophysial AVT was detected, but the neurohypophysis of the castrated males treated with EB contained less AVT than the neurohypophysis of the intact males. 6. Intact males had about twice as much MT in the neurohypophysis as females. Castrated males treated with either TP or EB had similar concentrations of neurohypophysial MT, which were lower than that of the intact males, but higher than that of the females. PMID- 2097039 TI - Incubation and maternal behaviour in domestic hens: influence of the presence of chicks on circulating luteinising hormone, prolactin and oestradiol and on behaviour. AB - 1. The consequences of the adoption of chicks and their subsequent removal on behaviour and plasma hormone concentrations of incubating hens were investigated. Birds were divided into two group: in group A, incubating hens were given chicks for 11 d; in group B chicks were left with the hens for 3 d only. 2. Incubating hens given chicks immediately showed maternal responses. The introduction of chicks induced a gradual nest desertion. Their removal stopped nest desertion temporarily on day 4 in group B hens. 3. Plasma prolactin concentrations fell one day after introduction of chicks and continued to decline for about one week in group A hens, although there was no further significant decrease in group B hens. Circulating prolactin tended to decrease with time in both groups. 4. Plasma luteinising hormone (LH) concentrations increased concurrently with the decrease of prolactin. The increase was more abrupt in group B hens. 5. Plasma oestradiol concentrations decreased slightly on the day chicks were introduced. The decline was arrested by removal of chicks in group B; in group A the tendency was reversed about 10 days after chick introduction. 6. Irrespective of group, before chick removal hens which deserted their nest rapidly had less contact with chicks and lower prolactin concentrations. PMID- 2097040 TI - Estimation of the quality of irradiated spermatozoa from cockerels using the classical method and zona-free hamster ova. AB - 1. The quality of gamma irradiated spermatozoa from cockerels was investigated by measuring motility, oxygen consumption and ability to penetrate zona-free hamster ova. 2. Doses of 750 Gy slightly reduced motility and oxygen consumption; however, irradiated spermatozoa penetrated on average 56% (minimum 33%) of hamster ova. 3. The zona-free hamster ova test may be useful for estimating avian sperm quality. PMID- 2097041 TI - Reproductive senescence in domestic fowl: effects on egg production, sequence length and inter-sequence pause length. AB - 1. Age-related changes in egg production, oviposition sequence length and inter sequence pause length were studied by analysis of oviposition records of 50 individually-caged broiler breeders from 24 to 62 weeks of age. 2. The 44 surviving hens exhibited a production profile characteristic of broiler breeders (184 eggs per hen), with a peak mean sequence length of 19 eggs at 32 weeks of age. Inter-sequence pause length was maximum (1.6 d) at 54 weeks of age. Overall, the hens averaged 48 sequences, with a mean sequence length of 4.1 d. 3. Most hens had a single characteristically long sequence about the time of peak egg production (average: 24.3 d). The term 'prime' is suggested to denote this sequence. 4. Sorting the hens into groups on the basis of total egg output (upper and lower 50% and upper and lower 25%) indicated that high producing hens (upper 50% and 25%) had a very long prime sequence early in lay, and had few inter sequence pauses of greater than 1 d duration. The converse was true for low producers (lower 50% and 25%). 5. The length of the prime sequence may be a good indicator of reproductive efficiency of hens later in life. PMID- 2097042 TI - Risks of having epilepsy. PMID- 2097043 TI - Dilantin hyperplasia: a preventable lesion? PMID- 2097044 TI - Prevention and treatment of Dilantin-associated gingival enlargement. PMID- 2097045 TI - Gingival overgrowth: hereditary considerations. PMID- 2097047 TI - Hypnosis, Part III: Uses in dentistry. AB - This article will discuss the uses of hypnosis in selected dental situations. In certain cases, the verbalization of the dentist during the procedural steps will be condensed or referenced in the literature. PMID- 2097046 TI - Vertical dysplasias and myofascial pain dysfunction syndrome. AB - The word myofascial describes the muscles (myo, Greek) and connecting tissue (fascia, Latin) of the face. This article discusses a group of symptoms that involves pain in the muscles around the face. PMID- 2097048 TI - Differential diagnosis of white and red/purple lesions in HIV-infected individuals. PMID- 2097050 TI - Median rhomboid glossitis: review of a puzzling entity. AB - This article discusses changing theories concerning median rhomboid glossitis (MRG). MRG is an uncommon lesion and when improperly diagnosed may be confused with carcinoma. PMID- 2097049 TI - Assessment of endodontically treated teeth for restorative procedures. AB - This article describes a case report in which cementation of cast posts and cores in endodontically treated upper central incisors resulted in extrusion of zinc phosphate cement into the periapical tissues. This case demonstrates the necessity for careful evaluation of existing endodontic therapy before proceeding with the restorative phase of treatment. Some primary indications for endodontic re-treatment are suggested. PMID- 2097051 TI - General dentist and periodontist working together. AB - An orthodontist, endodontist, or pedodontist, whether in teaching, private, or clinical practice, should be as alert and attentive to the maintenance of periodontal health as is a general practitioner or periodontist. The complete dental team is responsible for the health care of the dentition and supporting tissues of the mouth. This article is directed primarily to the general practitioner and periodontist. It relates to the team approach in this phase of oral health care and the mechanism and technique of referrals. There is an art to the referral protocol and proper communication among the general practitioner, periodontist, and patient. PMID- 2097052 TI - A serious complication following the inadvertent injection of sodium hypochlorite outside the root canal system. AB - During an attempt to negotiate a calcified root canal in a maxillary lateral incisor, a midroot distobuccal perforation was created, and sodium hypochlorite (NaClO) was extruded through the opening into the supporting tissues. This procedural accident caused an immediate burning sensation, severe pain, and marked facial swelling, with the subsequent loss of the tooth. PMID- 2097053 TI - Acute dental pain, Part 1: Diagnosis and emergency treatment. AB - The diagnosis and emergency treatment of acute dental pain that arises from periodontal or pulpal involvement are presented. Part I of this two-part series investigates periodontal-related emergencies that manifest as abscesses, cysts, and necrotizing ulcerative gingivitis (NUG). An attempt is made to clarify the differences among these emergencies by presenting their commonly associated symptoms and suggesting a logical approach to diagnosis and treatment. PMID- 2097054 TI - Oral herpetic lesions in an edentulous patient. AB - This article reports a case of oral herpetic lesions that recurred several times over 1 1/2 years in an edentulous 65-year-old woman. The patient was under treatment for complete dentures at the New Jersey Dental School. A differential diagnosis of mucosal ulcerative lesions is described, along with the laboratory methodology for confirmation of herpes simplex virus type 1 (HSV-1) infection. PMID- 2097055 TI - Use of a prefabricated splint for segmental augmentation of the mandibular alveolar ridge with hydroxyapatite. AB - Hydroxyapatite is a biocompatible material for augmentation of edentulous ridges to improve patient comfort and denture stability. The problems associated with hydroxyapatite are generally related to the amount of material introduced and the site of implantation. This article describes the use of a prefabricated splint that permits localization of the implant material to selected sites of the mandible and restricts the amount of material used. Fabrication of this splint under the guidance of the prosthodontist and oral surgeon permits the most effective use of this technique. PMID- 2097056 TI - Acute dental pain, Part II: Diagnosis and emergency treatment. AB - Part II of this two-part series differentiates and explores endodontic-related emergencies with reversible and irreversible pulpitis. Indications and contra indications for vital pulp therapy are explained, and treatment is outlined. The inflammatory process involved in irreversible pulpal disease is summarized, and the clinical signs, symptoms, and treatment of irreversible pulpitis (with and without acute periradicular involvement, with pulp necrosis, and acute periradicular abscess with and without cellulitis) are discussed. PMID- 2097057 TI - Prosthetic replacement of congenitally missing teeth using single-tooth osseointegrated implants: a case report. AB - This article presents the use of single-tooth implants in the rehabilitation of a 17-year-old patient with congenitally missing teeth. Treatment options are discussed, and advantages of the use of osseointegrated fixtures in the rehabilitation of partial anodontia patients are presented. A dental team approach is advocated. PMID- 2097058 TI - Management of teeth with open apexes and necrotic pulps: representative cases. AB - This paper briefly reviews the pros and cons of five methods used to treat a tooth with a necrotic pulp and an open apex (incompletely developed root), and presents representative treatments of open apex cases. These treatments include customized cone, short-fill, periapical surgery, apexification, and one-visit apexification. PMID- 2097060 TI - Becoming a more compassionate dentist by improving interpersonal skills. AB - Because of exposure to violence and other acts of inhumanity common today, there is a danger that the dentist could lose sensitivity for members of society and some sense of what it means to be human. This article reviews possible actions a dentist can take to ensure that the patient receives necessary attention during treatment. PMID- 2097059 TI - Posts, points, and instruments: how to retrieve them, Part 1. AB - Retrieving metallic objects from teeth and canals produces anxiety, particularly if the dentist retrieving the object placed it there purposely, as in the case of a post, or inadvertently, as in the case of an accidental separation. Part I of this two-part series describes three methods that can be used to retrieve such objects. Case reports are used to exemplify each method. This series cannot turn the experience into an enjoyable one, but it will point out some ways to remove unwanted fragments from root canals. PMID- 2097061 TI - Spontaneous rhythmic contractile behaviour of aortic ring segments isolated from pressure loaded regions of the vasculature. AB - STUDY OBJECTIVE: The aim was to study contractile responses of segments of rat arteries taken from pressure loaded and pressure protected regions and to examine the role of endothelial derived factors on the spontaneous activity of pressure loaded ring segments. DESIGN: Rats were subjected to complete aortic coarctation between the origins of the renal arteries and allowed to recover for 8 d. After 8 d arterial pressures were measured in awake animals from the pressure loaded and pressure protected regions simultaneously. Ring segments (2-3 mm) were taken from the two regions and mounted in a tissue bath for isometric force measurements. Similar studies were conducted in sham animals and in animals in which the kidney distal to the coarctation had been removed. EXPERIMENTAL MATERIAL: Female Sprague Dawley rats, weight 200-250 g, were used. MEASUREMENTS AND MAIN RESULTS: Eight days after coarctation mean aortic pressure proximal to the occlusion was 168(SEM 1.29) mm Hg (n = 104) while distally it was 38(2.42) (n = 40). Of the rings tested 96% showed spontaneous rhythmic activity, having a mean frequency of 3.94(0.17) cycles.min-1. Spontaneous activity was not present in the pressure protected segments taken from the same animals. Rats with the distal kidney removed (n = 25) failed to become hypertensive and similarly prepared ring segments failed to show spontaneous rhythmic activity. Prior removal of the endothelial layer had no effect on the spontaneous contractile responses in pressure loaded segments. Histological examination showed that the media to lumen ratio was increased in coarcted rats in both pressure loaded and pressure protected regions compared to similar regions in sham operated animals. CONCLUSIONS: Pressure loaded arterial segments show spontaneous contractile activity when compared to sham segments by mechanisms not dependent on endothelial derived factors. The increase in pressure proximal to the occlusion is dependent on the renin-angiotensin system, since pressure was not increased when the distal kidney was removed. We hypothesise that the chronic pressure load induces fundamental changes in membrane permeability which leads to spontaneous contractile activity. PMID- 2097063 TI - Evidence for an intrinsic mechanism regulating heart rate variability in the transplanted and the intact heart during submaximal dynamic exercise? AB - STUDY OBJECTIVE: The aim was to assess the changes in sympatho-vagal balance which occur with exercise. DESIGN: The power spectrum of RR interval fluctuations (low frequency [LF] and high frequency components [HF]) was determined before, during, and after graded work load exercise on a cycle ergometer. The power spectrum of the respiratory signal, oxygen consumption, and respiratory volumes were also evaluated. In all subjects HF was considered to be an index of respiratory sinus arrhythmia. In normal subjects HF and LF were considered to be indices of relative vagal and sympathetic activity, respectively, whereas in heart transplant subjects HF was considered as a respiratory modulation of the intrinsic heart rate, and not dependent on autonomic tone. Heart rate variability was evaluated as RR interval variance. SUBJECTS: 15 normal subjects (six trained cyclists and nine healthy sedentary subjects) and six orthotopic heart transplant recipients took part in the study. MEASUREMENTS AND MAIN RESULTS: During the first part of exercise, heart rate increased, RR interval variance decreased, HF decreased, and the relative amount of LF increased both in sedentary and athletic subjects, suggesting a relative increase in sympathetic tone. However, when approaching peak exercise, while heart rate further increased and the variance slightly decreased, the relative proportion of LF decreased and HF proportionally increased. At peak exercise HF accounted for 99.9% of heart rate variability in athletic subjects and for 88.9% in sedentary subjects (p less than 0.001 v baseline and v LF in both groups). In heart transplant subjects both the variance and the HF increased from the beginning of exercise (p less than 0.05), and showed a direct correlation with ventilatory variables and an inverse correlation with heart rate (r = 0.794, p less than 0.001, multiple regression analysis). No measurable LF components could be obtained in these subjects. During recovery, while the heart rate decreased and the RR interval variance increased, there was a relative increase in LF and a relative decrease in HF in normal subjects (either sedentary or athletic). Similarly, in heart transplant subjects, there was a decrease in HF during recovery. Thus the increase in HF at peak exercise in normal subjects contrasts with all the other data which suggest a prevalence in sympathetic tone during the entire exercise and the early recovery period, but appears similar to the increase in HF observed in heart transplant subjects due to the effect of increased ventilation during exercise. CONCLUSIONS: These findings suggest that at peak exercise a non-autonomic mechanism, possibly intrinsic to the heart muscle, may determine heart rate fluctuations in synchrony with ventilation in the intact as well as in the denervated human heart. PMID- 2097062 TI - Cardiovascular responses to graded treadmill exercise during the development of doxorubicin induced heart failure in rabbits. AB - STUDY OBJECTIVE: The aim was to examine the haemodynamic and humoral responses to graded treadmill exercise, serially during the development of congestive heart failure. DESIGN: Doxorubicin (1 mg.kg-1) was given to rabbits twice weekly intravenously over 8 weeks to induce a low output congestive cardiomyopathy. Treadmill exercise at 8 and 16 m.min-1 was performed at weeks 0, 2, 4, 6, 7, and 8. During each exercise study, continuous recordings were made of cardiac output, mean arterial pressure, and heart rate, and central venous blood was sampled at rest and during the last 10 s of exercise for plasma noradrenaline and plasma renin activity. EXPERIMENTAL MATERIAL: Six cross-bred English rabbits, mean weight 2.6 kg, received doxorubicin treatment; three control rabbits received vehicle injection. MEASUREMENTS AND MAIN RESULTS: Over the first 2 weeks, resting haemodynamic variables and responses to exercise were normal in all rabbits. Thereafter, doxorubicin treated rabbits had progressive falls in resting cardiac index and mean arterial pressure, and rises in resting heart rate and systemic vascular resistance. The normal increases in cardiac index and mean arterial pressure with exercise were progressively attenuated, despite an increase in resting and exercising heart rate. The resting levels of plasma noradrenaline and plasma renin rose after the fourth week of doxorubicin treatment. Throughout the experiment, exercise consistently raised plasma noradrenaline and renin, but the exercising levels of both hormones increased as heart failure progressed. Four of the six doxorubicin treated rabbits became exhausted in the final run and there was an intense rise in systemic vascular resistance. CONCLUSIONS: In this rabbit model of chronic heart failure, sympathetic vasoconstrictor drive is greater than normal at rest, and is greatly exaggerated during exercise. It is suggested that this abnormal response to exercise results from a combination of failure of arterial pressure to reach the elevated set point of the arterial baroreflex, increased afferent input from exercising muscles due to their underperfusion, and increase in central command due to muscle fatigue. PMID- 2097064 TI - Myocardial pathology in rats exposed to prolonged environmental heat. AB - STUDY OBJECTIVE: The aim was to assess the role of continuously high environmental temperature in the genesis of tropical cardiomyopathies. DESIGN: Rats were kept in a climatic chamber at a constant temperature of 34 degrees C (40% relative humidity) for 1 or 2 months. Controls were kept at 24 degrees C. The hearts, either taken directly from the animals or following Langendorff perfusion, were then examined by light and electron microscopy. EXPERIMENTAL MATERIAL: 69 rats of two different strains, aged about 1 month, were used as the study group. There were 32 suitable controls. MEASUREMENTS AND MAIN RESULTS: The weights of the heated rats and their hearts were lower than controls but the body to heart weight ratio was unchanged. The maximum pressure developed by the left ventricle was higher. With light microscopy, focal necrosis, lymphoid and mast cell infiltrations, fibrosis, and occasional calcifications were seen in most heat exposed rats. With electron microscopy most myocytes appeared normal when taken from whole animals. The additional trauma of heart suspension or hypo osmolar perfusion caused severe membrane related pathology, while controls remained unaffected. CONCLUSIONS: Prolonged exposure to heat produces focal cellular reactions and disturbance of the myocyte membrane. The pathogenesis of the changes is as yet uncertain. It may be multifactorial and include calcium and/or oxygen derangements mediated by mast cells, catecholamines, hypothyroidism, and heat shock proteins. PMID- 2097065 TI - Intracoronary endothelin-1 increases coronary retrograde pressure by constricting arterioles. AB - STUDY OBJECTIVE: The aim was to determine the site of coronary vasoconstriction induced by endothelin, by investigating the response in terms of retrograde pressure and reactive hyperaemia. EXPERIMENTAL MATERIAL: Twelve anaesthetised mongrel dogs, 12-14 kg, were used for the studies. DESIGN: The left anterior descending coronary artery was cannulated and perfused with blood through an extracorporeal bypass. The effects of intracoronary endothelin-1 (1-500 pmol) on coronary blood flow, coronary flow reserve (the peak reactive flow and the repayment after 15 s coronary occlusion), and retrograde coronary pressure during coronary occlusion were studied (n = 7). The retrograde coronary flow was collected from the bypass at each dose (n = 5). MEASUREMENTS AND MAIN RESULTS: At doses of greater than 20 pmol the coronary flow decreased dose dependently and reached almost zero flow at 500 pmol. The coronary flow reserve also decreased; however, the retrograde pressure was raised dose dependently at doses of greater than 10 pmol. At a dose of 500 pmol, the retrograde pressure was increased to 61 mm Hg [82(SEM 12)% of the coronary perfusion pressure]. Retrograde flow remained unchanged throughout the experiment. CONCLUSIONS: The endothelin-1 induced rise in retrograde pressure is in accordance with a dose dependent reduction in coronary flow reserve, and collateral flow was not augmented by endothelin. It is concluded that the effect of endothelin-1 on coronary circulation in situ was mainly due to the constriction of small resistant vessels. PMID- 2097066 TI - Protective effects of calcium channel blockers on hydrogen peroxide induced increases in endothelial permeability. AB - STUDY OBJECTIVE: The aim was to examine the effects of calcium channel blockers on the permeability of endothelial cells and to determine whether these agents could protect against increases in endothelial permeability induced by hydrogen peroxide (H2O2). DESIGN: Endothelial cells were cultured on collagen coated micropore filters. When they were confluent on the filter, albumin transfer and electrical resistance across the endothelial monolayers were measured. EXPERIMENTAL MATERIAL: Endothelial cells were obtained from human umbilical veins. The cells at the 2nd to 4th passage were used for the experiments. MEASUREMENTS AND MAIN RESULTS: Nilvadipine (10(-8) M) suppressed endothelial albumin transfer by 37.2% (p less than 0.01) and enhanced electrical resistance by 25.8% (p less than 0.01), whereas nicardipine (10(-7) M), diltiazem (10(-7) M), and verapamil (10(-7) M) had no significant effect on either variable without the addition of H2O2. H2O2(0.2 mM) increased albumin transfer by 164% (p less than 0.01) and reduced electrical resistance by 67% (p less than 0.01) across endothelial monolayers without endothelial cell lysis. Nilvadipine (10(-8) M) and nicardipine (10(-7) M) inhibited the (0.2 mM) H2O2 induced increases in endothelial albumin transfer and decreases in electrical resistance more strongly than diltiazem and verapamil, although all of these agents significantly reduced such injury. CONCLUSIONS: Nilvadipine is a potent inhibitor of endothelial permeability and of hydrogen peroxide induced increases in permeability. PMID- 2097068 TI - The cellular mechanism of circadian rhythms--a view on evidence, hypotheses and problems. AB - A stable period length is a characteristic property of circadian oscillations. The question about whether higher frequency oscillators (0.5-8 hr) contribute to or establish the stable circadian periodicity cannot be answered at present. A sequential coupling of quantal subcycles appears possible on the basis of known "ultradian" oscillations. There is, however, no supporting evidence for such a concept. Phase response curves of the circadian clock derived from various perturbing pulses allow qualitative conclusions concerning the perturbed clock process. Deductions from computer simulations also allow conclusions about the phase of this oscillatory process. The distinction between processes (a) essential to the clock mechanism, (b) maintaining and controlling the clock (inputs) and (c) depending on the clock (outputs) on the basis of "oscillatory" and "change of psi or tau after perturbation" seems to be useful but not stringent. Protein synthesis may be an essential or input process. Oscillatory changes of this process may be due to periodic translational control or RNA supply. Circadian changes in protein concentration and/or activity may depend on periodic synthesis, proteolysis, covalent modifications or aggregations. Specific essential proteins have not been identified conclusively. The large overlap between the group of agents and treatments that phase shift the clock and the group that induces stress proteins suggest that the latter may play a role in the controlling (input) or essential domain. The role of membranes in the clock mechanism is not clear: concepts assuming an essential function are based on circumstantial evidence. The membrane potential as well as Ca2+ may be involved in either input or essential function. Ca(2+)-calmodulin may also be important as concluded from inhibitor experiments. It is tempting to assume that a calmodulin dependent kinase is part of a periodic protein phosphorylation process, yet it is not clear whether the periodic protein phosphorylation that has been observed is essential or is just another output process. PMID- 2097067 TI - Coronary reactivity in the porcine heart after short lasting myocardial ischaemia: effects of duration of ischaemia and myocardial stunning. AB - STUDY OBJECTIVE: The aim was to characterise reactive hyperaemia and endothelium dependent (ADP) and independent (adenosine) vasodilatation after ischaemic periods of increasing duration, and in the stunned myocardium. DESIGN: The left anterior descending coronary artery was occluded 5-7 cm distal from its origin for consecutive periods of 2, 2, 5, 10, and 2 min separated by 30 min of reperfusion. Coronary flow was continuously measured by Doppler flowmetry proximal to the occlusion site. ADP and adenosine were infused into the left coronary artery proximal to the flowprobe. EXPERIMENTAL MATERIAL: 11 domestic pigs, weight 25-36 kg, were used. MEASUREMENTS AND MAIN RESULTS: In the stunned myocardium maximal reactive hyperaemia after 2 min of ischaemia was preserved, whereas all other variables describing reactive hyperaemia were diminished: time to maximal hyperaemia by 40% (p less than 0.01), duration of hyperaemia by 44% (p less than 0.001), volume of hyperaemia by 53% (p less than 0.001), and repayment of flow debt by 43% (p less than 0.001). The vasodilating effects of ADP and adenosine (dose-response curves) were not altered after development of stunning. CONCLUSIONS: Preserved maximal hyperaemia and vasodilation during ADP and adenosine infusion, but reduced volume of hyperaemia, indicate normal coronary reactivity but diminished release in the stunned myocardium of the vasodilator(s) responsible for the prolonged postischaemic flow increase. PMID- 2097069 TI - The influence of the athymic mutation nude on the components of the circadian rhythm of activity in mice. AB - The mutation known as nude brings about the lack of a thymus gland in mice. This immunodeficiency akes it possible to graft normally unaccepted, human cancerous tumors onto the mouse. Consequently, this animal is frequently used as a model for evaluating anti-cancer therapies. The effect of this mutation on biological rhythms constitutes a necessary step before using this model for cancer chronotherapy research. We evaluated the circadian and ultradian components of the rest-activity cycle in the following strains of mice: C57BL/6 with homozygous nu/nu, heterozygous nu/+, thymectomised +/+, and sham-operated +/+. The amount of activity was reduced in nu/nu as compared to the other groups. Nonetheless, neither the nude mutation nor thymectomy yielded any notable change in the circadian rhythm of activity. PMID- 2097070 TI - Circadian rhythmicity in the rat exocrine pancreas: chronomorphological patterns. AB - Circadian rhythmicity of the structural morphometric model of rat endocrine pancreas has been studied in 24 Wistar female rats, four months old, kept in LD 12:12. The following parameters were evaluated: the volume fractions of nucleus and cytoplasm of exocrine cells, the size distribution and number in unit tissue volume of acinar cell nuclei, the mean nuclear diameter, the shape coefficient of glandular acini (that is the ratio acinar area/perimeter2 which indicates the shifting of structures from circularity). A statistically significant circadian rhythm was demonstrated for the shape coefficient of glandular acini. Results obtained in the present experiment are compared with data recorded in a previous study. PMID- 2097071 TI - Characteristics of food-entrained circadian rhythms in rats during long-term exposure to constant light. AB - Rats possess a system of circadian oscillators that permit entrainment of circadian activity rhythms independently to 24 hr cycles of light-dark and food access. The nature of interactions between food- and light-entrainable oscillators was examined by observing the generation and persistence of food entrained circadian rhythms in rats whose light-entrainable rhythms were eliminated by long-term exposure to constant light. Most of these rats showed a delayed generation of food-entrained rhythms and only one of eight animals showed persistence of food associated rhythms during a 4-day food deprivation test. Rats whose light-entrainable rhythms are eliminated by suprachiasmatic nuclei ablation show, in contrast, normal generation and persistence of food-entrained rhythms. The results suggested a disruptive influence of constant light on non-photic entrainment, possibly due to coupling forces between damped light-entrainable oscillators and the food-entrainable oscillators. PMID- 2097072 TI - Gentamicin-induced chronotoxicity: use of body temperature as a circadian marker rhythm. AB - Aminoglycoside antibiotics produce varying degrees of ototoxicity, dependent on dosage time, in animals synchronized for rhythm study. Herein, we illustrate the use of an economical and reliable system to telemeter body temperature of laboratory animals as an endogenous marker rhythm for gentamicin-induced ototoxicity. Two groups of 3 male Sprague-Dawley rats (250-400 gm) were housed in separate cages in a temperature-controlled room programmed with a 12:12 LD schedule and monitored for hearing thresholds at the frequencies of 8kHz, 16 kHz, 24 kHz and 32 kHz at 2-week intervals. Each rat was dosed with 100 mg/kg/day gentamicin subcutaneously for a duration of 28 days. The animals from one group were dosed at their daily temperature maximum, while the animals of the other group were dosed at their daily temperature minimum. Both after 14 and 28 days of gentamicin treatment there was no important changes in auditory thresholds from baseline values when treatment was timed daily to the circadian peak of body temperature. Animals dosed daily at the trough of the circadian temperature rhythm evidenced an auditory threshold shift of between 5 and 25 dB after 14 days of treatment and a total hearing loss (80-90 dB) after 28 days of such treatment. These results document a dramatically greater level of hearing loss induced in those animals dosed with gentamicin at the body temperature trough (diurnal rest span) as compared to those dosed at the acrophase (nocturnal activity span). The findings indicate that the peak and trough of the circadian pattern of body temperature serve as meaningful markers of the resistance and susceptibility, respectively, of gentamicin-induced ototoxicity in rodent models. PMID- 2097074 TI - Circadian rhythm of trehalose in the face fly Musca autumnalis de Geer. AB - Trehalose levels were determined over two 24 hr spans in groups of face fly adults 3-4 days after emergence from the puparium. Face fly pupae were placed in rearing chambers at 27 degrees C in a staggered light-dark regimen, LD 16:8, so that at a given clock hour, samples could be obtained at several different hours after lights on (HALO). Trehalose was determined in hemolymph collected from a puncture in the intersegmental membrane of the abdomen. Treated hemolymph samples were passed through a Bio-Rad Amino 5-S disaccharide column and a Waters 410 refractive index detector was used to differentiate among sugars. The circadian acrophase derived by cosinor analysis in hemolymph trehalose (when the values were 25.49 and 26.86 micrograms/microliters on the first and second days respectively) occurred at -226 degrees (ca 15 HALO) and the bathyphase at 24 HALO. The mesor = 11.82 micrograms/microliters trehalose, the amplitude = 8.57 micrograms/microliters trehalose and the P-value for presence of a rhythm was 0.003. Based on these data, differences between control and test flies in a bioassay of hypertrehalosemic activity would be most easily observed at 0-8 HALO, while exogenous hypotrehalosemic activity would be best assayed at 12-20 HALO. PMID- 2097073 TI - Temporal variation in the effects of warfarin on the vitamin K cycle. AB - In this in vivo study, the time-dependent effect of oral sodium warfarin was studied in male rats synchronized under a 12-hr light-dark cycle (light 0600 1800). Groups of 5 animals received an oral dose of 500 micrograms/kg of warfarin or saline at 0600 or 1800 and 1 mg/kg of vitamin K 8 hr later and the rats were sacrificed 240 min after vitamin K administration. The activities of the vitamin K reductase and vitamin K epoxide reductase were measured indirectly by determining the content of vitamin K1 and vitamin K epoxide reductase in the plasma and liver. The data obtained in control rats indicated that vitamin K and vitamin K 2,3 epoxide concentrations in plasma and liver were higher (P less than 0.05) at 1800 than at 0600. Warfarin had a greater (P less than 0.05) inhibitory effect on the vitamin K and vitamin K-epoxide reductases at 0600 compared to 1800; plasma levels of S- and R-warfarin did not vary with time of administration. The findings suggest that the activity of both reductases under control conditions, and the warfarin-induced inhibition of these enzymes varied depending on the time of drug administration. PMID- 2097075 TI - Role of corpus allatum on the modulation of feeding rhythm in the semilooper caterpillar, Achaea janata (L). AB - A circadian feeding rhythm which may be entrained by photoperiod was found in fifth instar caterpillars of the lepidopteran, Achaea janata (L.). Allatectomy reduced the amount of food consumed; this consumption was significantly lower during the fifth instar in both allatectomized and sham-operated insects. An apparent circadian feeding pattern appeared on day 2 in the sham-operated caterpillars. Topical application of the anti-allatin, Precocene-II (50 micrograms/animal) also reduced leaf consumption significantly compared to the respective controls, although these controls maintained the same apparent circadian feeding rhythm on day 2. PMID- 2097076 TI - Removing masking factors from urinary rhythm data in humans. AB - We have previously developed simple models that enable the exogenous and endogenous components of the circadian rhythm of body temperature to be separated. The present paper extends the method to urinary data. First, we have shown that the basic superiority of the two-component model over the one component model persists when temperature data are converted into a format that is appropriate for urine sampling (that is, a single overnight sample and two hourly samples during waking). Second, we provide normative endogenous data for urinary sodium, potassium and urate, data obtained from about 80 constant routines. These data are required for the two-component model. Third, we have compared the rate of adjustment to a simulated eastward time-zone transition of 8 hr in 8 subjects. This showed that the rate of adjustment assessed by the two component model was significantly less than that assessed by the one-component model and much closer to that assessed in separate experiments (n = 15 subjects) using constant routines. We conclude that the two-component model can be used upon urinary data to give a closer approximation to the shift of the endogenous component, as assessed by constant routines, than can estimates that do not take into account the problem of masking caused by exogenous factors. PMID- 2097077 TI - Circadian distribution of proteins in urine from healthy young men. AB - Urine samples were collected at 3-hr intervals over a single 24-hr period from each of seven clinically healthy men who ranged in age from 21-25 years. Urines at each collection time were subsequently pooled using 20% of each volume and serially dialyzed against ammonium-barbituric acid buffer (pH 7.35 +/- 0.02), using a cellulose membrane permeable to compounds of less than 12,000-14,000 molecular weight (mw). When the dialyzed portions were then analyzed for total proteins, the sum of proteins in eight pools amounted to 74 mg. A 1 ml aliquot of each pool, representing approximately 50 micrograms of proteins, was concentrated and reconstituted. Approximately 20 micrograms of reconstituted proteins were then subjected to polyacrylamide gel electrophoresis. The stained gel was then scanned by laser densitometry and planimetry. Each aliquot revealed eight segments as identified by Coomassie and silver staining. Their molecular weights, estimated by extrapolation from concurrently run protein standards, and their total protein amounts were: 116,000 mw (9.44 mg), 91,000 mw (3.3 mg), 68,000 mw (11.58 mg), 53,000 mw (2.58 mg), 43,000 mw (9.12 mg), 32,000 mw (7.13 mg), 24,000 mw (4.52 mg) and 20,000 mw (5.27 mg). A statistically significant rhythm (P = 0.022 from ANOVA and 0.011 from Single Cosinor) was found for the excretion of total proteins, with an acrophase in the afternoon (1537) for these diurnally active subjects. PMID- 2097078 TI - Reference values for circadian rhythms of 98 variables in clinically healthy men in the fifth decade of life. AB - Nine clinically healthy men, 41-47 yr of age, served as subjects in a 24-hr study conducted at the Edward Hines Jr Veterans Administration Hospital in the Chicago area in May 1988. Physiologic measurements, and blood and urine samples were collected at 3-hr intervals over a single 24-hr period beginning at 1900. The number of variables measured or calculated (total = 98) included: 6 vital signs (oral temperature, pulse, blood- and intraocular pressures); 16 in whole blood (counts and differentials); 50 in serum (SMAC-24, lipids, hormones, electrophoresis of LDH and proteins); and 26 in urine (solids, proteins, creatinine, catecholamines, melatonin, cortisol, electrolytes and metals). Data were analyzed for time effect by analysis of variance (ANOVA) and for circadian rhythm by single cosinor. Individual rhythm characteristics for each variable were summarized for the group by population mean cosinor. The vast majority of variables revealed statistically significant within-day changes in values as validated by one-way ANOVA. All vital signs (except for intraocular pressures) and all serum hormones displayed a prominent circadian rhythm for the group, as did most variables in whole blood, while only about half of the variables in urine demonstrated a significant group rhythm. The results obtained are meant to: (a) document the circadian time structure; and (b) serve as reference values for circadian rhythm characteristics (range of change, mesor, amplitude and acrophase) for a defined group of individuals: clinically-healthy adult men in the prime of life. PMID- 2097079 TI - Effect of rubidium on the course of illness and the circadian rectal temperature in a 66-year-old depressive woman. AB - Rubidium (Rb+) has an antidepressive effect and shortens the circadian period in animals, whereas Li+, another alcalic metal, lengthens it. When we treated a depressive Li+ nonresponder with Rb+, we found an improvement of depression as well as a phase advance of the temperature rhythm in relation to the rest activity rhythm. PMID- 2097080 TI - Common migraine as a weekly and seasonal headache. AB - The aim of this study was to demonstrate that a possible recurrence may pertain to migraine attacks (MAs). The study was carried out by checking the personal diaries of 30 migraine sufferers ("migraineurs") who carefully annotated the date of their MA over twelve consecutive months. The group was composed of 15 males and 15 females, ranging in age from 17 to 37 years. The individual MAs were summarized in order to obtain the time-qualified frequency per each time period of recurrence. The periodicity in time data series was analysed by means of the Single Cosinor method. The rhythmometric analysis was found to be highly statistically significant; the circaseptan (P = 0.007) and circadian (P = 0.004) recurrence of MA showing critical incidence on Sunday and in January, respectively. No circatrigintan periodicity was validated in relation to the solar and lunar months or menstrual cycle. These findings suggest to us a possible linkage of MA to environmental factors which entrain the routine of our lives. Because of the circaseptan and circannual repetitivities, common migraine syndrome was defined as a "weekly and seasonal headache". PMID- 2097081 TI - Chronobiology and chronotherapy of cancer. PMID- 2097082 TI - The role of cellular proteases and their inhibitors in invasion and metastasis. Introductionary overview. PMID- 2097084 TI - Cathepsin B and its endogenous inhibitors: the role in tumor malignancy. AB - Several lysosomal proteinases including the cysteine proteinase cathepsin B have been implicated in malignant progression of tumors. Many investigators have demonstrated correlations between increased activity of cathepsin B and increased metastatic capability of animal tumors or malignancy of human tumors. Such increases in cathepsin B activity in malignant tumors may reflect alterations in synthesis, in activation and processing, and/or in intracellular trafficking and delivery as well as in the endogenous inhibitors of cathepsin B. Increases in mRNA transcripts for cathepsin B have been observed in both murine and human tumors and multiple transcripts for cathepsin B have been identified, but an association of multiple transcripts with malignancy has not been confirmed. Cathepsin B precursors found in human malignant ascites fluid do not possess mannose-rich carbohydrates suggesting that a defect in the post translational processing of carbohydrate moieties on tumor cathepsin B may be responsible for the release of cathepsin B observed in many tumor systems. However, the intracellular trafficking of cathepsin B responsible for its association with plasma membrane/endosomal systems and for its release will require further study as both latent, precursor forms of cathepsin B and native forms of cathepsin B are involved. We speculate that malignant tumor cells adherent to basement membrane are capable of forming a digestive microenvironment in which lysosomal proteinases such as cathepsin B function optimally, a microenvironment similar to that formed between adherent osteoclasts and bone. One of the endogenous cysteine proteinase inhibitors, stefin A, also is affected by malignancy. Reduced expression (mRNA and protein) of stefin A is found as well as a reduction in its inhibitory capacity against cysteine proteinases. The data to date at both the molecular and protein levels supporting a functional role(s) for cathepsin B and its endogenous inhibitors in cancer progression are only correlative. Experimental approaches utilizing well-defined model systems in conjunction with genetic manipulation of cathepsin B and its endogenous inhibitors are needed to provide convincing evidence that cathepsin B has an important role in cancer. PMID- 2097087 TI - Minor oral surgery for the general practitioner--apicoectomy. PMID- 2097085 TI - Mechanisms of trophoblast invasiveness and their control: the role of proteases and protease inhibitors. AB - Implantation and subsequent placental development in many species including the human are dependent on trophoblast invasion of the uterine epithelium, the underlying basement membrane, connective tissue and blood vessels. However, trophoblast invasion in situ is strictly controlled by the microenvironment provided by the pregnant uterus. Key mechanisms underlying various steps in trophoblast invasion of basement membrane and stroma are similar to those identified in the case of invasive tumor cells: (a) attachment to basement membrane by binding to laminin and possibly other basement membrane components; (b) detachment from the basement membrane matrix prior to its penetration, a process that requires the presence of complex-type oligosaccharides on the cell surface; (c) breakdown of basement membrane components by trophoblast-derived metalloproteases (type IV and interstitial collagenase) and serine proteases (plasminogen activator). Type IV collagenase activity is stimulated by binding to laminin, a molecule also secreted by the trophoblast. Activation of trophoblast derived metalloproteases appears to be plasmin-dependent. Plasmin results from the cleavage of plasminogen by trophoblast-derived plasminogen activator. Control of trophoblast invasion in situ is mediated by decidua-derived transforming growth factor beta (TGF beta) which in turn induces tissue inhibitor of metalloproteases (TIMP) both in the decidua and the trophoblast. We suggest that this control of trophoblast invasiveness is regulated both spatially as well as temporally during gestation. A preprogrammed decline in trophoblast invasiveness with increasing gestational age remains an additional possibility. The nature of the loss of control of trophoblast invasiveness in choriocarcinoma remains to be identified. Refractoriness to TGF beta action remains to strong possibility. PMID- 2097083 TI - Stromelysin in tumor progression and metastasis. AB - There are several characteristics of stromelysin that suggest that expression of this enzyme may play an important role in tumor invasion and metastasis; the stromelysin gene is expressed in response to stimulation by oncogenes and tumor promoters, and the protein product of this gene is a metalloproteinase capable of degrading multiple components of the extracellular matrix. Experimental evidence to support this hypothesis has been derived from several animal model systems, in which a positive correlation has been observed between stromelysin expression and tumor progression and metastasis. In addition, in vivo experiments in which the levels of TIMP, the tissue inhibitor of metalloproteinases, were altered also strongly suggest a causal role for metalloproteinases in tumor metastases. The expression of active stromelysin in tumor cells requires the fulfillment of several criteria, and this multistep process is reminiscent of the molecular events that are currently understood to contribute to tumor progression and carcinogenesis. Expression of stromelysin mRNA requires both a stimulus, a step which may correspond to the activation of an oncogene in multistep carcinogenesis, as well as the lifting of transcriptional repression, which may correspond to the loss of tumor suppressor function. Both positive and negative modulation of stromelysin transcription appear to utilize pathways that involve the protooncogenes c-fos and/or c-jun. The expression of active stromelysin enzyme also requires conversion of the proenzyme to an active form, and a proper balance between the expression of inhibitors and the levels of active enzyme. The multiple levels of stromelysin regulation support the concept of multistep carcinogenesis and may provide a tool for further understanding of the molecular nature of the events that lead to tumor progression, invasion, and metastasis. PMID- 2097088 TI - Complete dentures for elderly patients. PMID- 2097086 TI - Proteases in the schistosome life cycle: a paradigm for tumour metastasis. AB - Cancers and parasites have a number of properties in common, particularly those that relate to their respective capacities to evade host defence mechanisms. This review highlights the similarities between metastatic tumours and schistosomes in particular, and describes the role that proteases may have in the migration, growth, survival and transmission of the different stages of the schistosome life cycle in the vertebrate host. An elastase-like serine protease of schistosome larvae has been particularly well characterized, and its substrate profile and other properties are indicative of a role in facilitating migration of the parasite through skin tissue early after infection. The primary structures of a cathepsin B-like enzyme, and a putative 'haemoglobinase' found in adult worms have also recently been derived, these enzymes being responsible for degradation of haemoglobin in erythrocytes upon which the adults feed. Adult schistosome worms reside and produce eggs intravascularly, and the processes that mediate the extravasation and subsequent migration of the egg through host tissue are dependent on both blood platelets and the immune response. Fibrino(geno)lytic enzymatic activity that is present in the egg could modulate the thrombogenic potential that eggs might have as a result of their capacity to cause platelet aggregation in vitro and in vivo. The roles of other proteases and peptidases that have been found in schistosome larvae, worms and eggs are less clear. Some of these enzymes may modulate immunological and haemostatic defence mechanisms and thus prolong survival of the parasite, and the consequences of the interactions between schistosomes and host protease inhibitors could also be immune modulatory. PMID- 2097089 TI - Study of the eruption times of the permanent dentition of the children in Israel. PMID- 2097090 TI - UK Prospective Diabetes Study 6. Complications in newly diagnosed type 2 diabetic patients and their association with different clinical and biochemical risk factors. AB - The prevalence of various diabetic complications, their association with each other and with many risk factors, has been assessed in 2,337 newly diagnosed Type 2 diabetic patients. The patients entered into the UK Prospective Diabetes Study were aged between 25 and 65 (mean age 52 yr) and 33% had either an abnormal ECG or retinopathy. Different macrovascular complications such as strokes, heart attacks or abnormal ECG, and peripheral vascular disease showed little association one with another, and each was associated predominantly with different risk factors, e.g., strokes with hypertension, heart attacks with hypertriglyceridaemia and peripheral vascular disease with smoking and a low HDL cholesterol. Retinopathy was associated with reduced vibration perception but not with other complications. Reduced vibration perception and absent reflexes were associated with absent foot pulses and ischaemic skin changes, raising the possibility of a macrovascular, as well as microvascular, contribution to peripheral neuropathy. Microalbuminuria was associated with hypertension, which might be a factor predisposing to renal microvascular disease or be a consequence of it. Microalbuminuria was also associated with an abnormal ECG. Retinopathy, with exudates and or haemorrhages rather than just microaneurysms, was associated with hyperglycaemia. The occurrence of a particular complication in a diabetic patient is probably dependent on a combination of specific risk factors, many of which are related to, and probably affected by, potentially avoidable factors such as hyperglycaemia, obesity, smoking and hypertension. PMID- 2097091 TI - Autoantibodies in the sera from newly diagnosed diabetic nod mice: evidence against cross-reactivity with a putative beta-cell surface autoantigen. AB - In insulin-dependent diabetes mellitus in humans, the BB rat and the NOD mouse, serum has been reported to contain autoantibodies that precipitate a 64,000 Mr protein from (32S) methionine labeled histoincompatible non-autoimmune rat or mouse islet cell proteins. Because experimental data reported recently have brought into question the role of the 64,000 Mr protein in targeting autoantibodies and hence initiate beta-cell destruction, we report differently designed experiments to clarify the apparent 64,000 Mr autoantigen enigma. Using an in vitro model of NOD mouse origin mimicking diabetic insulitis we found that target beta-cells induced a 6-fold increase in proliferative response of splenic L3T4+, Thy-1,2+ T cells. The magnitude of the proliferative response was not affected when target beta-cells were pretreated with 50% (vol/vol) partially purified immunoglobulins ((NH4)2SO4 precipitation at 33% saturation) from sera from newly diagnosed (less than 4d after onset) diabetic NOD mice. Cytofluorimetric analysis of beta-cells pretreated with partially purified immunoglobulins plus FITC-conjugated goat antimouse IgG as a second-step antibody were negative and thus gave no indication of an autoantigen-autoantibody complex formed on the surface of the beta-cells. We conclude from the experimental data that it remains still in question whether an autoantigen is targeted by an islet cell surface specific autoantibody and plays a role as a triggering event in the pathogenesis of diabetes in NOD mice. PMID- 2097092 TI - Effects of diets rich in sucrose, coconut fat and safflowerseed oil on the development of the obese hyperglycaemic (ob/ob) syndrome in mice. AB - The effect of dietary sucrose and fat in the form of coconut fat (rich in saturated fatty acids) or safflowerseed oil (rich in polyunsaturated fatty acids) was examined on the development of obesity and impaired glucose homeostasis in ob/ob mice. Isoenergetic high sucrose or high fat diets were fed to ob/ob mice from 3-11 weeks of age. Energy intake of mice fed diets rich in fat were similar, and exceeded that attained with the sucrose diet. Body weight gain was greatest in the sucrose-fed mice and least in those fed safflowerseed oil. With the exception of insulin sensitivity which was enhanced with safflowerseed oil, plasma concentrations of glucose and gastric inhibitory polypeptide (GIP), glucose tolerance, intestinal GIP content and the GIP response to oral fat were similar. However, mice fed the high sucrose diet exhibited markedly elevated plasma insulin concentrations and an enhanced pancreatic insulin content. Since the hyperinsulinaemic action of sucrose cannot be attributed to elevated GIP or glucose concentrations, the involvement of other insulin-releasing hormones released from the intestine by sucrose is suggested. The results indicate that the relative amounts of carbohydrate and fat in the diet have an important modulating effect on the development of the ob/ob syndrome. The type of fatty acids in the diet does not appear to be a particularly important determinant for expression of the ob gene. PMID- 2097093 TI - Transplantation of islets of Langerhans isolated by Trowell's T8 medium in outbred rats: effect of cyclosporine. AB - This study was carried out to investigate the efficacy of cyclosporine to prolong islets isolated by collagenase in Trowell's T8 medium and Ficoll gradient separation. Our results demonstrate that a short course of cyclosporine is effective in minimizing rejection of transplanted islets in outbred rats. PMID- 2097094 TI - Insulin secretion in rats: effects of neuropeptide Y and noradrenaline. AB - Neuropeptide Y (NPY) occurs within nerves in the rat pancreas, some of which are adrenergic. Therefore, we examined the influence of NPY alone and together with noradrenaline (NA) on insulin release in the rat. When infused alone for 30 min under basal conditions, NPY increased basal plasma insulin concentrations by 32 +/- 13 microU/ml at the highest dose level tested (68 pmol/min), as compared to +7 +/- 7 microU/ml in the controls (p less than 0.05). In contrast, NPY at 17 pmol/min reduced the plasma insulin response to both glucose (by 11%; p less than 0.001) and to arginine (by 26%; p less than 0.001). Infusion of NA alone (340 pmol/min) significantly elevated the basal plasma insulin levels by 41 +/- 4 microU/ml (p less than 0.001). NPY (17 pmol/min) completely abolished this effect (p less than 0.001). When NA (340 pmol/min) was added to an ongoing glucose infusion, the plasma insulin levels were markedly reduced (by 48%; p less than 0.001). By introducing NPY (17 pmol/min), this inhibitory action occurred more rapidly. However, NPY did not affect the maximal response to NA. In isolated rat islets, both NPY (10(-6) M) and NA (10(-6) M) inhibited glucose-stimulated insulin secretion. However, the maximal inhibitory effect exerted by the two neurotransmitters was not altered by giving them together. We conclude that, in the rat, NPY and NA both elevate basal plasma insulin levels and inhibit stimulated insulin secretion. In combination, NPY also induces a more rapid onset of the inhibitory action of NA on glucose-induced insulin secretion. PMID- 2097095 TI - Glucose turnover in BHE rats fed EFA deficient hydrogenated coconut oil. AB - The effects of feeding corn or hydrogenated coconut oil on various parameters of glucose metabolism in prediabetic BHE rats was studied. Weanling rats were fed a 6% fat-64% sucrose diet. At seven weeks of age, the rats were weight matched within diet treatments. Half of the rats were injected with 6(3)H/U14C glucose while their weight matched counterparts were injected with U14C alanine and 3HOH. Diet had no effect on glucose mass, glucose space, hepatic glycogen or blood glucose levels. However, diet did affect other parameters. HCO fed rats had higher fractional irreversible glucose turnover rates, fractional glucose carbon recycling, hepatic fatty acid synthesis rates, adipose fatty acid synthesis rate, lower muscle glycogen and lower rates of incorporation of glucose into muscle glycogen than corn oil fed rats. These differences in glucose flux explain the maintenance of glucose homeostasis in these prediabetic coconut oil fed rats in the face of increased fatty acid and glucose synthesis. PMID- 2097097 TI - Playing phone tag to win. PMID- 2097096 TI - Crossing state lines. WICHE grads tell their stories. PMID- 2097098 TI - Filling niches for dentists. PMID- 2097099 TI - Should we set standards? PMID- 2097100 TI - The protective effect of mepacrine on acute lung edema induced by phorbol myristate acetate in rats. AB - A good model of adult respiratory distress syndrome is lung injury induced by phorbol myristate acetate (PMA). In the present study we examined the effect of mepacrine, an inhibitor of phospholipase A2, on lung injury induced by PMA in isolated blood-perfused rat lungs. In the isolated lung, saline (1 ml) or mepacrine (75 microM) alone in the perfusion system did not discernibly change the pulmonary arterial pressure (PAP) and lung weight (LW). After administration of PMA (0.16 micrograms/ml), severe hypertension and lung edema developed (delta PAP = 40.1 +/- 6.0 mmHg, p less than 0.001; delta LW = 5.5 +/- 0.7 g, p less than 0.001). Whereas, the addition of mepacrine (75 microM) prevented PMA-induced lung edema and pulmonary hypertension (delta PAP = 4.7 +/- 2.2 mmHg, delta LW = 0.2 +/ 0.2 g). To further elucidate the protective mechanism of mepacrine on lung injury, a vasodilator (nitroprusside) was given to decrease PAP levels to +6 mmHg from baseline values in the PMA group, as well as in the mepacrine-pretreated PMA (MPMA) group. During a subsequent venous pressure challenge, severe lung injury developed in the PMA group (delta LW = 9.5 +/- 2.1 g, p less than 0.001). However, with the same venous pressure challenge in the MPMA the lung weight was markedly less than that of the PMA group (delta LW = 1.0 +/- 0.2 g). Histologic findings examined by light microscopy presented intraalveolar hemorrhage and fluid accumulation, disruption of vascular basements and alveolar septa, and aggregation of inflammatory cells within the parenchyma in the lungs of the PMA group. In the MPMA group there was no evidence of intraalveolar hemorrhage and alveolar fluid accumulation, however, the occasional presence of granulocytes in the parenchyma and slight interstitial edema were still observed. In addition, depressed the chemiluminescence release from PMA activated granulocytes which were in a dose-dependent manner in vitro. These observations suggest that mepacrine inhibits PMA-induced lung injury chiefly by protection of vascular permeability. The mechanism of the protection may be due to the inhibition of oxygen radicals released from activated neutrophils and the reduction of neutrophil chemotaxis. PMID- 2097101 TI - Potentiated depression of indirectly evoked twitch tension of rat soleus muscle following arterial blood occlusion in the presence of ketamine. AB - The presence of ketamine, in a dose insufficient to depress the indirectly evoked twitch tension of soleus muscle, was shown to significantly potentiate the depression of the indirectly evoked twitch tension following a 10-min occlusion of the arterial blood to this muscle. Since ketamine was known to be an uncoupling agent in oxidative phosphorylation, it was possible that its uncoupling property potentiated the effect of the 10-min blood occlusion to depress the indirectly evoked twitch tension of soleus muscle. PMID- 2097102 TI - Effects of biogenic amine precursors on ovarian steroid-induced LH release in acutely ovariectomized rats. AB - Effects of catecholamines and indoleamine precursors on the luteinizing hormone (LH) release induced by estradiol (E2) and progesterone (P4) in acutely ovariectomized (Ovx) rats were studied. Rats were Ovx on diestrus day 1 (D1) and received a spaced injection of E2 and P4 on D1 and D2, respectively. One of the following substances: L-beta-3, 4-dihydroxyphenylalanine (L-DOPA), DL-threo dihydroxyphenylserine (DOPS), or 5-hydroxy-L-tryptophan (5-HTP) was administered intraperitoneally at 0900h on the expected diestrus day 2 (D2). The control group received saline. Serial blood samples were collected in the afternoon of D2 and plasma concentrations of LH were measured by radioimmunoassay. Results indicate that E2 and P4-induced LH release could be facilitated, but not significantly, by DOPS, delayed/inhibited by L-DOPA, and completely inhibited by 5-HTP as compared with saline controls. Exogenous administration of luteinizing hormone releasing hormone (LHRH) induced significantly higher LH release in E2/P4-primed Ovx than in control Ovx rats. Results imply that the classical neurotransmitters in the central nervous system might modify the threshold of LHRH neurons in the hypothalamus. PMID- 2097103 TI - Serotonin-stimulated prolactin secretion may not involve the dopaminergic system. AB - The possible involvement of the dopaminergic system in the serotonin (5-HT) stimulated prolactin (PRL) secretion was tested in this study. Adult female rats were ovariectomized for two weeks and treated with estrogen (polyestradiol phosphate, 0.1 mg/rat, sc) for 6 days before use. They either received pretreatment with alpha-methyl-p-tyrosine (250 mg/kg BW, ip), a dopamine (DA) synthesis inhibitor, or two DA antagonists, domperidone and haloperidol (0.1 mg/kg BW, iv) before receiving 5-HT (1 mg/kg BW, iv) or quipazine (1 mg/kg BW, iv), a 5-HT agonist. Blockade of DA synthesis or antagonism of DA action invariably induced elevated plasma PRL levels. 5-HT or quipazine, however, could still induce significant PRL secretion on top of the increased PRL levels. Minor difference was found between the action of domperidone and that of haloperidol. In conclusion, the dopaminergic system may not be involved in the action of 5-HT to stimulate PRL secretion. PMID- 2097104 TI - Induction and repression of specific estradiol sensitive proteins in the rat corpus luteum. AB - In the pregnant rat estradiol causes luteal cell hypertrophy and a dramatic increase in overall protein synthesis. The aim of this investigation was to determine whether estradiol induces the synthesis of specific proteins in luteal cell subcellular fractions and to examine estradiol-regulated translational products in order to identify a specific protein marker of estradiol action in the corpus luteum. Corpora lutea obtained from day 12 hypophysectomized hysterectomized pregnant rats treated with or without estradiol (2 cm implant) for 3 days were incubated with Trans35S-label for 8 hours at 37 degrees C in an atmosphere of 95% O2 - 5% CO2. Nuclear, mitochondrial, microsomal and cytosolic subcellular compartments were obtained by differential centrifugation. RNA was extracted and translated using a rabbit reticulocyte lysate reaction mixture. Radiolabeled proteins were separated by SDS-PAGE, visualized by fluorography and quantified by densitometry. Estradiol-treatment significantly increased 35S-amino acid incorporation into luteal proteins. Specific estradiol-induced proteins within cellular fractions included mitochondrial 80, 50, and 32 x 10(-3) Mr proteins; microsomal 100, 80, 32 x 10(-3) Mr proteins; and cytosolic 80, 60, 50 and 14 x 10(-3) Mr proteins. Estradiol-treatment increased the secretion of two proteins (60 and 45 x 10(-3) Mr) while no major estradiol-induced proteins were noted in the nuclear fraction. In vitro translation of mRNA indicated that estradiol markedly enhances the message for a protein with apparent Mr 32 x 10( 3) Mr. The 32 x 10(-3) Mr translated protein appeared as the major estradiol induced protein in mitochondrial and microsomal fractions. Estradiol also reduced the expression of a 38 x 10(-3) Mr protein (pI 7.0) in the cytosolic compartment. The major estradiol sensitive protein observed in luteal particulate and translation profiles was a 32 x 10(-3) Mr protein with a pI greater than or equal to 8.5. This protein may serve as a potential protein marker of estradiol action in the rat corpus luteum. PMID- 2097105 TI - [The parathyroid risk in thyroid surgery. Argument against the early postoperative prescription of vitamin D. Experience with 729 thyroidectomies in 1988]. AB - 729 consecutive patients underwent thyroidectomy in 1988 in the same institution, including 477 (68%) bilateral resections and 242 (33%) total thyroidectomies. An effort was made to see and save all 4 parathyroids and their blood supply. Early post-operative hypoparathyroidism was defined at day 5, by serum calcium less than 8 mg/dl. and serum phosphate less than 4 mg/dl or by serum calcium only if greater than 7.5 mg/dl. Patients afflicted with early hypoparathyroidism were given calcium tablets without any vit D for 1 year at most. Follow-up, checking serum Ca, P and i PIH was done on a 3 months basis during 1 year. Permanent hypoparathyroidism was defined by persistence of the above-mentioned criteria after 1 year, and eventually vit D was started. 27 patients (5.6% our of 477 bilateral thyroid resections) experienced early post-op hypoparathyroidism. Inciting factors were previous thyroid surgery (4), radioiodine treatment (2), modified neck dissection (2), sternal split with mediastinal node clearance (1), visualization of 1 parathyroid gland only (3 redo cases) and autotransplantation of more than 1 parathyroid (1 case). 1 patient was lost for follow-up. 25 others recovered a normal parathyroid function. 1 is permanently hypoparathyroid (1 redo case with other risk factors). Painstaking parathyroid dissection allows a 0% rate of permanent hypoparathyroidism after primary surgery, if vit D is not given in the early post-operative period. We suggest that avoidance of early vit D prescription in cases of early post-operative hypoparathyroidism, leading to mild sustained hypocalcemia, stimulates the spared parathyroid glands (including a possible 5th) and therefore allows full recovery of the parathyroid function. PMID- 2097106 TI - [Surgical research in France. Evaluations and prospects]. PMID- 2097107 TI - [Antenatal diagnosis of obstructive uropathies]. AB - Many cases of low or bilateral obstructive uropathy due to malformations lead to death, either in utero or at birth, as the absence of diuresis leads to oligoamnios, which in turn causes hypoplasia of the lungs that does not allow neonatal survival. The associated chromosomal anomalies or multiple malformations also have harmful effects. These severe prenatal forms had not been taken into account for pediatric statistics, and were previously not studied. Thus it proved essential for prenatal medicine not to be content with arriving at diagnoses, but rather to try and foresee the prognosis of the abnormalities revealed by assessing the renal function of the fetus in each case. A number of data on fetal urine, such as the sodium, 2-microglobulin or calcium levels, make this assessment possible. Correlations between the fetal urinary parameters and the renal function in the child at age one have been established. These criteria now allow distinguishing the fetuses that will not survive from those that will have renal insufficiency and, finally, from those whose renal function will be normal at age 1. PMID- 2097108 TI - [Digestive physiopathology of the fetus]. AB - The evolution en enzymatic activity in the amniotic fluid follows the various stages of development of the gastrointestinal tract during pregnancy. Before 12 weeks of amenorrhea, no enzymatic activity can be detected, as this period corresponds to the persistence of the pharyngeal and anal membranes. At 13-14 weeks, a very high level of enzymatic activity is suddenly observed in the amniotic fluid, reaching its peak at 16-18 weeks. This phase corresponds to the opening of the pharyngeal membrane, the appearance of swallowing and the opening of the anal membrane. After 18 weeks, the digestive enzyme level progressively decreases until 22-24 weeks, after which date no gastrointestinal enzymatic activity can be evidenced in normal fetuses (probably because of functional anorectal obstruction). We have determined the enzymatic anomalies related to some gastrointestinal deformations (duodenal atresia, cystic fibrosis, atresia of the bile ducts, anorectal atresia). PMID- 2097109 TI - [Role of fetal surgery in the treatment of abnormalities. Apropos of diaphragmatic hernia]. AB - Therapeutic operations on fetuses have been attempted for the first time in the 60's. The major problem for obstetricians at that time was the Rh incompatibility, and Lilley performed the first successful intraperitoneal intrauterine fetal blood transfusion in 1963. Since then the attempts have become increasingly numerous, and experiments in animals proved their feasibility and surgical safety both for the mother and for the fetus. The possible advantages of fetal surgery are not readily assessed, and the indications for fetal surgery can currently be justified only if the natural history of the malformation is known, the physiopathology of the affected organ studied, and the correction of the anatomical abnormality proved to produce the resumption of organ development. The surgical indications should be discussed with practitioners not involved in the program, with the informed consent of the parents, and all the results, whatever they be, should be communicated to the medical community. PMID- 2097110 TI - [Prenatal medicine: what responsibility?]. AB - Prenatal diagnosis demands technical and human choices from both the parents and the practitioners, which require a real dialogue. The actual legal problem raised by prenatal diagnosis is much less a problem of responsibility than one of information. PMID- 2097111 TI - [Antenatal diagnosis and ethical problems]. AB - The fast development of techniques detecting diseases or malformations of the fetus during the 2nd third of pregnancy has led to a real evolution in our knowledge. We can recognize minor or major abnormalities, as well as many hereditary or acquired diseases. This revolution raises considerable ethical problems because, at the same time, our ability to receive and operate the children with malformations as early as birth is ever improving. And yet the mothers often ask for induced abortion. What are we supposed to do? What are the acceptable limits? PMID- 2097112 TI - Students at risk: chemical dependency & the dental student. PMID- 2097113 TI - Nitrous oxide becomes the vice of dentists. PMID- 2097114 TI - Amalgam controversy: an update for dental students. PMID- 2097115 TI - Antiamalgamists move amalgam controversy into legislatures. PMID- 2097116 TI - Radiovisiography reduces dentist, patient exposure to harmful x-rays. PMID- 2097117 TI - Dental students should not neglect getting immunization against hepatitis B. PMID- 2097118 TI - Up to snuff? Students voice concerns on tobacco use. PMID- 2097119 TI - [The antimutagenic action of amino acids on UV-irradiated E. coli cells: the demonstration of the existence of metabolic regulation of the antimutagenic activity]. PMID- 2097120 TI - [The discovery of a possible cell receptor for the tick-borne encephalitis virus (TBE) by using anti-idiotypic antibodies to viral protein E]. PMID- 2097121 TI - [The pharmacokinetics of zosterin--a pectin from the eelgrass Zostera asiatica]. PMID- 2097122 TI - [The motor innervation of the skeletal neck muscle in the mouse]. PMID- 2097123 TI - [The effect of typhoid endotoxin on erythrocyte membrane resistance in vitro]. PMID- 2097124 TI - [Krezatsin--an experimental stimulant of the activity of regenerating hepatocytes]. PMID- 2097125 TI - [Acid polypeptides as inhibitors of the repair of double-stranded DNA breaks induced by the gamma irradiation of HeLa cells]. PMID- 2097126 TI - [The possibility of the circulation of vaccinal influenza A viral strains in the biosphere]. PMID- 2097127 TI - [The autodyne diffraction radiation generator method for research on biological objects]. PMID- 2097128 TI - [The desensitization kinetics of nicotinic cholinoreceptors depends on intracellular ATP]. PMID- 2097129 TI - [Calorimetric proofs for 2 conformational states of the myosin subfragment-1 complex with nucleotides]. PMID- 2097130 TI - [New findings in the mechanics of human forced breathing in a gaseous environment of extremely high density]. PMID- 2097131 TI - [Regulation of the motor activity of the chick embryo amnion. The role of serotonin and catecholamines]. PMID- 2097132 TI - [The immobilization of enzyme-membrane complexes--a new approach to creating highly efficient biocatalysts]. PMID- 2097133 TI - [The serum element (SRE)--the probable target for the negative control in the regulation of the proto-oncogene c-fos promoter]. PMID- 2097134 TI - [The cellular activity of the brain limbic structures in a conflict situation]. PMID- 2097135 TI - [The zone of human thermal neutrality in heat adaptation]. PMID- 2097136 TI - [The redox potential of the rabbit cerebral cortex during hypnosis (immobilization stress)]. PMID- 2097137 TI - [The characteristics of heat-shock protein synthesis in the blood cells of the camel Camelus dromedarius]. PMID- 2097138 TI - [The age-related characteristics of skeletal muscle regeneration in guinea pigs]. PMID- 2097139 TI - [The coordination of the mitotic stability of the genetic structures and the radiosensitivity of saccharomycete yeasts]. PMID- 2097140 TI - [The effect of x-ray irradiation on the "cell cycle-dependent" expression of the proto-oncogenes c-fos and c-Ha-ras in the hepatocytes of rat regenerating liver]. PMID- 2097141 TI - [The expression of the human interleukin-2 gene in Escherichia coli bacteria]. PMID- 2097143 TI - Ramoplanin versus methicillin-resistant Staphylococcus aureus: in vitro experience. AB - The authors have investigated the activity of ramoplanin against 162 isolates of MRSA from some twenty-six countries around the world. MICs were determined by the plate dilution method in isosensitest agar with an inoculum of 10(6) cfu. MBCs were measured by replication, using velvet pads, from MIC plates after 24 h incubation at 37 degrees C. Time-kill curves were determined from viable counts of cultures in Isosensitest broth (inoculum ca. 5.0 x 10(6) cfu/ml) taken at intervals during shaking culture at 37 degrees C for up to 24 h. Ciprofloxacin, mupirocin, rifampicin, teicoplanin and vancomycin were used as comparison compounds. The following MIC90 (MBC90) values (mg/l) were obtained against a selection of 60 strains: ciprofloxacin 0.8 (1.8), mupirocin 0.27 (19.0), ramoplanin 0.5 (1.0), rifampicin 0.007 (0.01), teicoplanin 1.2 (greater than 32) and vancomycin 2.2 (greater than 32.0). In time-kill experiments, ramoplanin at 20 mg/l and ciprofloxacin at 3.0 mg/l produced 99.9% killing in less than 4h. Mupirocin at 4.0 mg/l was only slowly bactericidal. No resistance was found to mupirocin, ramoplanin, teicoplanin or vancomycin in the 162 isolates tested, whereas ca. 20% resistance was found to ciprofloxacin and rifampicin. The absence of resistance, the high intrinsic activity and the rapid bactericidal effect of ramoplanin against this diverse group of MRSA are very encouraging, and suggest that clinical trials are indicated. PMID- 2097142 TI - [The identification of the binding sites of nuclear factor I in the region of the bovine beta-casein gene]. PMID- 2097144 TI - Efficacy of dactimicin plus clindamycin compared with gentamicin plus clindamycin in the treatment of experimental intra-abdominal infections in rats. AB - A reproducible experimental model of intra-abdominal infections in rats has been developed in order to simulate intra-abdominal sepsis in patients. A 1-cm segment of ileum was isolated on its vascular pedicle. The intestine was then divided at each end of the segment and intestinal continuity was re-established by an end-to end anastomosis. Dactimicin is a new aminoglycoside antibiotic with a broad antibacterial spectrum including both aerobic Gram-positive and Gram-negative bacteria. The experimental model was used to compare the efficacy of dactimicin in combination with clindamycin with the combination gentamicin/clindamycin in the treatment of intra-abdominal infections. Of the untreated animals, 70% died within two days. Animals treated with dactimicin plus clindamycin or gentamicin plus clindamycin exhibited significantly decreased mortality and increased cure rates during the experimental period. Only 5% of these animals died. Thus the combination dactimicin/clindamycin seems to be useful in the treatment of intra abdominal infections. PMID- 2097145 TI - Biliary elimination and hepatic disposition of a new fluoroquinolone, temafloxacin: experimental evaluation. AB - Temafloxacin is a new quinolone derivative presently under evaluation. Its pharmacokinetic profile, and particularly its biliary elimination and hepatic disposition, remains undefined. The present study describes an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for 3h (h) with reconstituted blood in a closed circuit; 10 mg of temafloxacin were added to the circulating blood at the onset of the procedure. Bile was recovered throughout the experiments and liver fragments were taken at the conclusion. Assays were carried out by high-performance liquid chromatography. Pharmacokinetic analysis was performed with reference to a monocompartmental open model. Under these conditions, the serum half-life of temafloxacin was 3.1 and the maximal biliary concentration of 19.3 +/- SEM 3.1 micrograms/ml was reached between 30 and 60 min; the cumulative biliary elimination (0-3 h) amounted to 92 +/- 16 micrograms (0.9% of the added dose). Total and hepatobiliary clearances were calculated as respectively 134 and 2.38 ml/h and the hepatobiliary elimination rate as 0.0042 (h-1). At the end of the procedure, 25.7 +/- 3.5% of the added dose of temafloxacin was still present in the circulating blood, and 13.7 +/- 2.4% in the liver. Degradation of the antibiotic in the perfusion device concerned only 2.4% of the dose. The percentage of temafloxacin undergoing hepatic biotransformation, determined by subtraction, was high (57.3%). Under these experimental conditions, temafloxacin appears to be particularly stable in serum, poorly eliminated as parent compound in the bile, highly fixed in the liver and above all subject to a probable hepatic biotransformation. Extrapolation of these experimental data to other species or to the whole organism would be hazardous, but these results should stimulate studies on a possible hepatic metabolism of this new trifluoroquinolone in man. PMID- 2097146 TI - Antibiotic susceptibility of periurethral anaerobic microflora in healthy girls. AB - The in vitro susceptibility of sixty-four isolates of periurethral anaerobic bacteria to nine commonly used antibiotics was analyzed. Using a quantitative sampling method, the three predominant anaerobic strains were isolated from each periurethral sample of twenty-one healthy prepubertal girls. The majority of strains showed high sensitivity to ampicillin and phenoxymethylpenicillin, whereas trimethoprim and trimethoprim--sulfamethoxazole showed no or only slight inhibition of growth of most strains. Intermediate sensitivity was found to erythromycin, cefuroxime, pivmecillinam, norfloxacin and nitrofurantoin. Our data suggest that several antibiotics used in paediatric praxis might influence the indigenous periurethral anaerobic microflora. Hypothetically, this may be a factor of importance in the pathogenesis of ascending urinary tract infections. PMID- 2097147 TI - Topical antibiotic therapy: current status and future prospects. AB - As we enter a new decade, topical antibiotics are the subject of much renewed interest and are being used on a wider scale than ever before. The reasons for using topical rather than oral therapy for a variety of dermatoses include the reduced risk of systemic side effects, the avoidance of resistance selection in the gut microflora, the higher achievable concentration of antibiotic at the site of action and the overall usage of less drug. Somewhat surprisingly, treatment costs are not reduced by the use of topical therapy. The number of antibiotics licensed for topical use has increased in recent years and now includes representatives of the tetracycline, macrolide, lincosamide, aminoglycoside and peptide families of antibiotics in addition to fusidic acid, chloramphenicol and pseudomonic acid. Opinions regarding the clinical efficacy of topical antibiotics are conflicting, and for most indications alternative oral therapies are available. Topical antibiotics are the drugs of choice for the elimination of nasal carriage of Staphylococcus aureus and for the therapy of eye and external ear infections. They are also effective in the treatment of impetigo and other superficial pyodermas and in the management of localised infected eczema. Topical preparations of erythromycin, clindamycin and tetracycline are widely prescribed for the therapy of acne and are of clinical benefit in mild--moderate cases. However, they are no more effective against inflamed lesions than benzoyl peroxide and are less effective against non-inflamed lesions. They are not as effective as oral tetracycline in moderate to severe acne and should not be considered as a therapy for severe acne, for which 13-cis-retinoic acid is the drug of choice. It is well known that many antibiotics, when used topically, especially for prolonged periods, select for antibiotic-resistant staphylococci at the skin surface. Tetracyclines, erythromycin and clindamycin also select for resistant staphylococci on the surface of intact skin when delivered by the oral route. The contribution of topical antibiotic usage to the current high level of antibiotic resistance in coagulase-negative staphylococci, which are increasingly implicated in infections of compromised hosts, has not been quantified, although it is known that cutaneous staphylococci possess a large pool of transferable resistance genes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2097148 TI - Preoperative serum CA-125 levels in early stage ovarian cancer. AB - Preoperative serum CA 125 levels were elevated in only 23% (9/39) of patients with FIGO Stage I invasive ovarian epithelial carcinoma whereas 88% of patients with Stages II-IV disease had elevated CA 125 levels preoperatively. No preoperative serum CA 125 levels in any patient with Stage I disease exceeded 300 U/ml. PMID- 2097150 TI - The modifications of T-lymphocyte cell subpopulations in patients with beta interferon intracavitary treatment. AB - 18 patients with malignant genital or mammary neoplasia, treated with endocavitary Beta-Interferon (intrapleural or intraperitoneal), were examined in order to study the modifications of T-lymphocyte subpopulations (T3, T4, T8, T4/T8) in the peripheric blood. An improvement in the immune state in complessively 50% of the patients treated was observed, while there were no modifications in the remaining patients (in 3 patients with advanced ovarian cancer there was persistence of immunodepression preexisting to treatment). This indicates that endocavitary Beta-Interferon induced very poor immune response at peripheric level (contrary to what other Authors have described at peritoneal level), correlated to the dose used and to the extent of serous surface exposed to the drug. PMID- 2097149 TI - Randomized comparison of cyclophosphamide, doxorubicin and cisplatin (CAP) versus cyclophosphamide and doxorubicin (CA) for the treatment of advanced ovarian cancer (ADOVCA). A EORTC Gynecological Cancer Cooperative Group Study. AB - The possible advantage of adding cisplatin (P) to cyclophosphamide (C) + adriamycin (A) in the management of stages III and IV ovarian cancer of epithelial origin was tested in a trial in which 149 patients were randomized to receive, after initial surgery, either CAP (C = 600 mg/sqm, A = 45 mg/sqm, P = 50 mg/sqm) or CA (C = 600 mg/sqm, A = 45 mg/sqm) every 4 weeks for 6 to 12 cycles, at which time follow-up laparotomoy was to be performed in responding or clinically disease-free patients. Fifteen patients were not included in the final analysis and the remaining 134 patients were considered fully or partially evaluable and are used in analysis of response and survival. The complete and partial response rates were 45.6% in the CAP arm and 45.4% in the CA arm, but the CAP regimen is of special importance in patients with bulky disease. Median survival CAP = 24 m and CA = 24.2 m), time to progression and survival was found not significantly different when CAP and CA were compared. However, more patients in the CA regimen had no macroscopic disease left after surgery than in CAP regimen (11 versus 6) and more patients in the CAP arm dose reductions and schedule delays than in the CA arm (61.1% versus 38.2%). PMID- 2097151 TI - Placental alkaline phosphatase (PLAP)/PLAP-like alkaline phosphatase as tumour marker in relation to CA 125 and TPA for ovarian epithelial tumours. AB - The significance of the PLAP (Placental alkaline phosphatase)/PLAP-like isozyme as tumour marker in relation to CA 125 and TPA for the monitoring of patients with malignant ovarian epithelial tumours was evaluated. Of all patients (n = 85), 40% had all three markers elevated. CA 125 being the most sensitive (60%), and the PLAP/PLAP-like isozyme and TPA both 40%. A tendency to certain tumour marker patterns of these three antigens in serum can be seen with regard to histopathology. Serous and anaplastic adenocarcinomas usually have all three markers moderately elevated, mucinous and mesonephric adenocarcinomas both have low incidences and low average levels of all three markers. Endometrioid and non mucinous adenocarcinomas are often associated with high levels of the PLAP/PLAP like isozyme and CA 125, while TPA shows moderate elevation. The PLAP/PLAP-like isozyme is positively correlated to tumour burden and the outcome of the disease. It may provide additional information on CA 125 in the monitoring of patients with ovarian cancer. PMID- 2097152 TI - Endometrial cancer: our experience. AB - The Authors have referred to their experience based on 293 endometrial cancer patients operated at the II University Gynecological Clinic in Catania, between 1975 and 1989. Many prognostic indicators such as stage, histologic grade, myometrial invasion depth, lymph-node metastasis, non-neoplastic endometrium histology, tumor size and histology were studied; the Authors affirm the validity of two risk factors such as tumor size and the histology of the non-neoplastic endometrium, readily observable by hysteroscopy during the preoperative assessment and which are well correlated with the depth of myometrial invasion and lymph node methastasis. PMID- 2097153 TI - Serum CA 125, CA 15.3 and CA 19.9 levels and surgical findings in patients undergoing second look operations for ovarian carcinomas. AB - Sera from 52 ovarian cancer patients undergoing chemotherapy and second look operation were studied. CA 125, CA 15.3 and CA 19.9 assays were performed during chemotherapy and prior to relaparotomy. Twenty-six patients (50%) had no evidence of disease whereas 2 (3.8%) and 24 (46.1%) had microscopic and macroscopic disease. In general although the predictive value of an elevated CA 125 or CA 15.3 level is excellent, a normal value (less than 35 U/ml) has limited significance. Moreover, we found no improvement in negative predictive and positive predictive value by adding the determination of CA 19.9. PMID- 2097154 TI - The treatment of endometrial carcinoma: our experience in the period 1983-89. AB - The Authors evaluated 87 cases of endometrial carcinoma, of whom 65 (74.7%) at pathological stage I. The surgical ratio was (96.5% 84/87 cases), and 31 cases were subjected to adjuvant postsurgical Radiotherapy because of the presence of risk factors. The incidence of relapses resulted complessively in 14.2%, with a NED-survival of 86.1% and an overall survival of 91.9% at the pathological stage I. The Authors emphasise particularly the importance of post-surgical Radiotherapy in the cases at risk, which allowed an important decrease of the incidence of relapses at stage I with regard to previous studies. PMID- 2097156 TI - Experience in the treatment of epithelial ovarian carcinoma with cisplatinum containing combination chemotherapy and dose intensity calculation. AB - Twenty-six patients with epithelial ovarian carcinoma, were treated by cisplatinum--containing combination chemotherapy following initial laparotomy. The mean number of treatment cycles was 7.8 (median: 9). The mean dose intensity (DI) and mean relative dose intensity (RDI) respectively were for cyclophosphamide: 108 mg/m2/week and 0.65, for doxorubicin: 8.6 mg/m2/week and 0.51, and for cisplatinum: 9.8 mg/m2 week and 0.59. The mean average relative dose intensity (ARDI) was 0.53. The three-year survival for all patients was 43%. No statistically significant difference in the three-year survival between patients receiving RDI's and ARDI of less than median dose and those receiving RDI's and ARDI of more than median dose could be demonstrated. Larger series are needed to test whether, and to what extent, dose intensity contributes to outcome, independently of the total amount of drug given. PMID- 2097155 TI - Estrogen and progestin receptor levels in uterine leiomyomata: relation to the tumour histology and the phase of menstrual cycle. AB - Estrogen receptor (ER) and progestin receptor (PR) levels in the myometria and uterine leiomyomata of 26 normally menstruating women were studied. No significant menstrual cycle-related change in ER level was found in the leiomyomata or normal myometria. The ER levels in normal myometria and in cellular leiomyomata, but not in usual leiomyomata, tended to be higher in the follicular phase than in the luteal one. The "cytosolic" PR levels in cellular leiomyomata and in usual leiomyomata with no or with slight hyalinization as well as in their parental myometria were significantly lower in the luteal than in the follicular phase. This was not the case in usual leiomyomata with more intense hyalinization. The findings show that the reactivity of uterine leiomyomata to estrogens and/or progestins may be related to the histological features of the tumors. This should be realized when studying the steroid receptor levels in the tumours and possibly also when planning an endocrine therapy for the leiomyomata. PMID- 2097157 TI - Adenocarcinoma of a neovagina constructed according to the Baldwin-Mori technique. AB - The Authors describe a case of cancerization of a neovagina constructed according to the Baldwin-Mori technique, occurring 39 years after the initial operation. Description of the clinical case is followed by a number of anatomo-pathological considerations. The risk of cancerization and the adverse events associated with this type of neovagina militate against the use of autologous transplant operations in neovagina construction. PMID- 2097158 TI - Wertheim-Meigs operation in the Gynaecologic and Obstetric Institute of Sassari in the ten-year period 1980-89. AB - In a retrospective study we examined 42 radical hysterectomies according to Wertheim-Meigs in the ten year period 1980-89, of whom 39 for carcinoma of the cervix, two for endometrial carcinoma at stage II one for microinvasive vaginal carcinoma. The incidence of relapses was 11.9% (5 cases) globally, with 3.7% at pathologic stage I, while the actuarial survival was 95.4% at stage I. The intraoperative, perioperative and postactinic complications related to integrated treatment are described, underlining the importance of post-surgical Radiotherapy in cases at risk. PMID- 2097159 TI - Radioimmunoassay of corticotropin-releasing hormone. AB - A specific double antibody radioimmunoassay (RIA) for human-Corticotropin Releasing Hormone (hCRF) using an antibody to synthetic hCRF was established. This antibody allowed a usable range of 10 pg to 5 ng of CRF per ml in the assay. Comparing the efficiency of various plasma extraction procedures, the extraction with ice-cold methanol was found to be the most simple and rapid method with an extraction efficiency of more than 80%. The reliability of the radioimmunoassay was shown under physiological and pathophysiological conditions. PMID- 2097160 TI - Aldosterone content in plasma, erythrocytes and skeletal muscles in Icenko Cushing's syndrome. AB - Aldosterone concentration was measured in plasma, erythrocytes and skeletal muscles in 34 patients with Icenko-Cushing's syndrome (ICS). It was established that aldosterone levels in the erythrocytes and whole blood of these patients were elevated, while aldosterone content in the plasma and muscular tissue of the patients was normal. Only in a small group of patients (N = 4) aldosterone levels positively correlated with arterial pressure (BP) and central hemodynamic parameters. Following 10 minutes of headdown tilt (-15 degrees), erythrocyte aldosterone level in the group of healthy controls (N = 12) was markedly elevated, but not in the group of patients with ICS. The results of the study suggest that erythrocytes can be viewed as a mobile aldosterone "depot" and may operate to mediate depressor effects of certain hormones on central hemodynamics. PMID- 2097161 TI - Circannual oscillations of function compared with morphometric changes in the thyroid gland of the Wistar-rat. AB - To investigate biological rhythms of the thyroid gland circannual oscillations of thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) were compared in serum samples of untreated young male Wistar-rats with the circannual changes of thyroid weights and with the relative proportion of colloid, epithelium, and interstitium of the thyroids. Animals were kept under standard environmental conditions, however, lighting conditions simulated the natural day-night changes. Thyroid weights, T4, T3, and TSH showed a statistically significant circannual rhythm with maxima in winter and spring and minima in summer and autumn. The same circannual patterns were observed in the proportion of epithelium and interstitium of the thyroids, while the colloid exhibited an inverse circannual pattern. These data were verified by biomathematical methods, like locally adjusted functional approximation, analysis of variance, and Spearman rank correlation. Our results represent an example for the concordance between functional and morphometrical changes in the course of circannual oscillations. Furthermore, these data confirm our earlier results describing higher T4-levels in the winter time (short-day) and lower serum titers in the summer time (long day). PMID- 2097162 TI - Effect of estrogen-receptor interaction on the levels of fatty acid-binding proteins and spectra of free acids in small intestinal mucosa of rabbits. AB - Data on the possibility of estrogens to regulate absorption of free fatty acids (FFA) during absorption of lipids in small intestine with associated estrogen receptor interaction and changes in fatty acid-binding protein (FABP) levels are reported. In particular, characteristics of cytoplasmic estrogen receptors, estradiol metabolism, FABP levels and spectra of FFA in FABP fraction were studied in small intestinal mucosa of sexually mature and immature female rabbits, intact or after ovariectomy and estradiol dipropionate administration. The dissociation constants (Kd) and number of binding sites were determined in coordinates of Scatchard. FABP levels were demonstrated spectrophotometrically after ultracentrifugation (K-32M) and gel filtration (G-75). FFA composition of FABP fraction, chyme and enterocytes were analyzed by a chromatographic method (Tsvet-110). Levels of body estrogens were monitored by high-performance liquid chromatographic analysis (Tsvet-306) of estrogens in daily urine. The study has demonstrated a specific relation between FABP levels and their lipid component, FFA, on the one hand and endo- and exogenous estrogen levels on the other hand, in female rabbits maintained on a standard fat-free diet. PMID- 2097163 TI - Effect of calcitriol and trifluoperazine on glucose stimulated B cell function in healthy humans. AB - The authors investigated the effects of pharmacological doses of calcitriol (1,25(OH)2-vitamin D3) and trifluoperazine on metabolic and hormonal indicators of glycoregulation in the course of the intravenous glucose tolerance test (IVGTT) in healthy subjects. Calcitriol administered by the oral route for four days, 3 micrograms/d, did not alter the blood sugar and plasma IRI levels at rest nor glucose stimulated values throughout the IVGTT. The slight increase of the glucose assimilation coefficient was not significant, as compared with values of the control test (Kg = (3.9 +/- 0.5) x 10(-2) [min-1] vs. Kg = (3.4 +/- 0.3) x 10(-2) [min-1], respectively). C-peptide plasma levels after calcitriol were slightly higher, significantly during the 14th minute following glucose administration (p less than 0.05), while the two-peak shape of the curve was preserved. Trifluoperazine administered by the oral route for seven days, 10 mg/d, did not significantly affect the blood sugar, IRI and C-peptide values at rest nor glucose induced values throughout the IVGTT nor values of glucose assimilation (Kg = (3.0 +/- 0.4) x 10(-2) [min-1] vs. Kg = (3.4 +/- 0.3) x 10(-2) [min-1] in the control test). In conclusion, neither calcitriol nor trifluoperazine treatment leads to clinically significant alteration of glycoregulation. PMID- 2097164 TI - Effect of training on the performance of blood glucose monitoring using a reagent strip (Glucoprofil). AB - A relatively simple, new test-strip for blood-glucose monitoring, the Glucoprofil strip with a reaction-zone of film-foil, was evaluated by testing 100 different blood glucose concentrations between 2.1 and 29.7 mmol/l. The results were obtained visually before and after training to read the color changes of the strip according to the scale on the strip-container. Plasma glucose measurements with the Beckman Glucose-Analyzer were used for reference. The results show that the Glucoprofil-strip readings correlated well with the reference method (r = 0.97), thorough training provided. The mean deviation of the strip results was less than 1 mmol/l. Similar results were obtained using another blood glucose strip, the Haemoglukotest 20-800 R. Our study indicates that the performance of the Glucoprofil strip is satisfactory, and hence the strip may be useful for clinical purposes. Consistent with previous reports we could demonstrate that training improved the reading results of the Glucoprofil strip. PMID- 2097165 TI - Impairment of cardiorespiratory reflexes and its association with distal somatic neuropathy in diabetic patients free from clinical symptoms of autonomic neuropathy. AB - Signs of autonomic cardiac neuropathy and its association with distal somatic neuropathy were investigated in 36 type 1 and 28 type 2 diabetic patients free from clinical symptoms of autonomic neuropathy. Using bedside tests (deep breathing, Valsalva manoeuvre and lying-to-standing) definitive cardiac autonomic neuropathy was found in 28 patients (44%), early cardiac autonomic neuropathy was observed in 19 patients (30%) while 17 patients (26%) showed no alterations. The values of motor nerve conduction velocity in peroneal nerves (41.8 +/- 0.7 m/s, mean +/- SEM) were significantly (p less than 0.01) lower in patients with definitive cardiac autonomic neuropathy than those (45.8 +/- 1.1 m/s) of patients without any signs of cardiac autonomic neuropathy. These latter values were, however, significantly (p less than 0.001) lower than those (53.7 +/- 0.7 m/s) of control subjects (n = 50). Signs of early or definitive cardiac autonomic neuropathy were recorded in 31 of 35 diabetic patients with distal somatic neuropathy assessed by measurement of motor nerve conduction velocity in peroneal nerves. It was concluded that abnormal results of noninvasive tests for autonomic neuropathy, i.e. alterations in cardiorespiratory reflexes indicating parasympathetic impairment of cardiac innervation could be often found in diabetic patients without clinical signs of autonomic neuropathy. These alterations could be frequently observed in diabetic patients with distal symmetrical somatic neuropathy. PMID- 2097166 TI - Effect of sodium depletion on the renin-angiotensin-aldosterone system and renal prostaglandins in acromegalic patients. AB - The effects of 5 days low sodium diet and diuretic were studied in 7 normotensive acromegalics, 8 hypertensive acromegalics and 12 normal subjects. Plasma renin activity was significantly lower in both groups acromegalics, compared with that of normal subjects. Plasma aldosterone was similar in normotensive acromegalics and healthy controls. The hypertensive acromegalics showed increased plasma aldosterone levels and blunted responses of plasma renin activity and plasma aldosterone to sodium depletion. Urinary prostaglandin E2 was significantly lower in hypertensive acromegalics before and after sodium depletion in comparison with normal subjects. Urinary 6-keto prostaglandin F1 alpha and thromboxane B2 were similar in all groups studied. The decreased production of PGE2 could contribute to the development of arterial hypertension in actomegaly. PMID- 2097167 TI - Different response of porcine large and small luteal cells to PRL in terms of progesterone and estradiol secretion in vitro. AB - The extent of progesterone and estradiol secretion by isolated either large or small luteal cells was examined during incubation of separate cell types in medium without and with 100 ng/ml PRL. Small and large luteal cells were isolated from early corpora lutea of pig by means of Ficoll continuous gradient. The amount of progesterone released by large cells into the incubation medium was 5 fold higher than that by the small ones. In the presence of PRL large cells secreted more progesterone (1.5 fold) than the control ones. We did not observe any stimulatory effect of prolactin on progesterone secretion by small luteal cells. On the other hand, prolactin added to the medium decreased estradiol production by both cell types. PMID- 2097168 TI - Oxidative stress as a causal factor in differentiation and aging: a unifying hypothesis. AB - In this article, the authors have pointed out flaws in the current version of the free radical hypothesis of aging and have advanced a new hypothesis that reconciles and encapsulates existing information. The main premise of this hypothesis is that aging is a continuation of development and is thus influenced by genetically programmed phenomena. Completion of various genetic programs and the duration of life are linked to a metabolic potential which is itself a genetically determined sum of energy expenditure. Nevertheless, the rate at which metabolic potential is reached is linked to the rate of metabolism and the level of oxidative stress both of which are influenced by epigenetic stimuli. The current version of the free radical hypothesis postulates that partially reduced oxygen species are produced in aerobic cells in an uncontrolled fashion and do not play any useful physiological function. The principle tenet of the free radical hypothesis is that molecular damage is the underlying cause of aging and that O2- radicals and derivatives induce most of the damage sustained by cells during aging. The authors regard this hypothesis as flawed because it fails to explain either low randomly occurring damage can lead to age-associated changes that are species-specific, or the sequential nature of the changes that occur in aging organisms. In contrast to the free radical hypothesis, our hypothesis can explain the specific and sequential nature of aging-related changes because they are postulated to be neither dependent upon uncontrolled damage nor the cellular capacity to prevent it. Instead, the authors suggest that the damage accumulated during aging is a secondary effect rather than a direct cause of senescence. The authors have shown that cells exert control not only on their level of antioxidant defense but also on their rate of oxidant production. The authors postulate that aging is the terminal stage of development, and as such is influenced genetically. The authors also postulate that a definite sum of energy is required to complete the genetic programs associated with aging. Thus, the rate of aging is linked to the level of oxidative stress; the rate of energy utilization is postulated to determine the level of oxidative stress. Oxidative stress is one of the factors which appears to govern changes in gene expression during differentiation and we suggest that it causes alterations in gene expression during aging. In the authors revised hypothesis, free radicals promote aging by affecting specific genetic programs and the incidental damage they inflict in cells is only a by-product of this process.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2097170 TI - GABA content and synthesis in the aging rat brain. AB - The content and synthesis of GABA were measured in the cortex and striatum of young adult (4 months), mature (14 months), and old (24 months) male Wistar rats. GABA synthesis was determined from the GABA accumulation induced by aminooxyacetic acid (AOAA). Aging did not affect GABA content in the cortex (1.03 +/- 0.04 mumoles/g in young and 1.06 +/- 0.04 mumoles/g in old rats), or in the striatum (1.63 +/- 0.04 mumoles/g in young and 1.56 +/- 0.05 mumoles/g in old rats). Aging did not significantly change the AOAA-induced GABA accumulation in the striatum (+34% in young, +16% in mature, and +28% in old rats), but significantly reduced it in the cortex where this process takes place to a greater extent than in the striatum: +164% in young, +116% in mature, and +120% in old animals. It can be concluded that while in the striatum aging did not affect AOAA-induced GABA accumulation, in the cortex this was less in mature than young rats, with no further change in the old ones. GABA content was not affected by aging in either region. PMID- 2097169 TI - Body temperature rhythms, cold tolerance, and fever in young and old rats of both genders. AB - The circadian rhythm of body temperature (CTR) of male and female rats living at 23 degrees C, as well as their body temperature response to a yeast injection or to a 2-h exposure to 0 degree C, was investigated by telemetry. Young rats had a clear CTR with a mean nocturnal peak of 38.0 +/- 0.1 degree C and diurnal trough of 36.2 +/- 0.1 degree C. Older rats, starting at about 18 months of age, tended to have poor (that is, lower amplitude) rhythms. Mean daily body temperature was 37.1 +/- 0.2 degree C at all ages. After exposure to the cold, the body temperature of young rats, old rats with a strong CTR, and old rats with a poor CTR changed in the ranges of -0.3 to +1.5 degree C, -3.1 to +0.7 degree C, and 5.2 to +0.4 degree C, respectively. This indicates that old animals, especially but not exclusively those with poor CTRs, are less resistant to cold stress. On the other hand, the capacity to develop a fever in response to a yeast injection was equivalent in the three groups of animals, although females had a smaller response than males. It is concluded that the process of aging does not have a generalized debilitating effect on temperature regulation in rats. Rather, aging seems to affect individual components of the thermoregulatory system differentially. PMID- 2097171 TI - Strain specific respiratory air space enlargement in aged rats. AB - We studied lung structure and function in Fischer-344 and Sprague Dawley rats to compare the pathophysiologic features of the aged lung in animal strains. Both strains were maintained under identical conditions of minimal exposure to injurious environmental agents. We measured the number, size, and surface area of alveoli, pressure-volume characteristics and connective tissue content of lungs at midlife (12 or 14 months of age) and old age (24 months of age). Results showed differences in the older versus younger group of the Sprague Dawley strain as indicated by enlarged air spaces [154 +/- 21 (SEM) versus 118 +/- 13 micromicroliter] (p less than 0.05), increased collagen (hydroxyproline content 4.1 +/- 0.1 versus 3.0 +/- 0.1 mg/lung) (p less than 0.05), and a leftward shifted pressure-volume curve. There was no change in surface area or alveolar number. The structural lesions are consistent with air space enlargement with fibrosis and not emphysema. In contrast, no major changes were found in the lungs with age in Fischer-344 rats. We hypothesize that in the Sprague Dawley strain the aging process impairs the ability of the lung to maintain normal structure and function. Two strains of rats which differ pathologically in old age may be useful in the study of the effects of aging on the lung. PMID- 2097172 TI - Life span differences in digoxin uptake and excretion. AB - Little is known about the underlying mechanisms for the altered susceptibility to digitalis with age. To this end, we investigated the digoxin uptake and excretion in mice and rats of different ages through the life span, including the periods of growth, maturity, and aging. Digoxin uptake by cardiac slices was linear from 0 to 15 min, with steady state occurring at 45 min. The rate in the mature 12 month mouse was significantly less than that of the senescent 30-month mouse. The kinetic parameters revealed a significant decrease in Km with a concomitant increase in Vmax during senescence. On the other hand, digoxin uptake by renal cortical slices was highest during growth, decreased to a maturation plateau and then declined further during senescence. Renal clearance and the secretory capacity for digoxin increased 30 and 62%, respectively, during growth and progressively decreased from maturity through senescence and were 59 and 77%, respectively, during aging. In summary, there was an increase in digoxin clearance and tubular activity during growth, and an increase in myocardial uptake of digoxin and a decrease in renal excretion during aging. Thus, these results may explain the clinical observations of altered susceptibility to digitalis with age. PMID- 2097173 TI - Renal tubular cell or hepatocyte hyperplasia is not associated with tumor promotion by di(2-ethylhexyl)phthalate in B6C3F1 mice after transplacental initiation with N-nitrosoethylurea. AB - B6C3F1 mice of both sexes that had been exposed transplacentally on day 18 of gestation to 0.5 mmole N-nitrosoethylurea (NEU) were fed either normal diets or diets containing di(2-ethylhexyl)phthalate (DEHP) at 6,000 ppm beginning at 6 wk of age and continuing to 78 wk of age. At 52 and 78 wk of age, 6-26 mice from each group received a single injection of 5-bromo-2'-deoxyuridine (Brdu) at 200 mg/kg i.p. and were sacrificed 1 h later for determination of the levels of renal and hepatic DNA synthesis by the Brdu immunohistochemical technique. No differences occurred in incidences of gross or microscopic renal tubular cell tumors between the NEU (males 15%, females 21%) and NEU-DEHP groups (males 10%, females 15%) at 78 wk. The labelling index (LI) of renal cortical tubular cells was significantly increased at 78 wk (22.3 +/- 3.7/mm2 for males, 21.8 +/- 1.2 for females) in mice given NEU and DEHP as compared with NEU alone (9.7 +/- 1.0 for males, 6.9 +/- 0.7 for females). The number and sizes of focal hepatocellular proliferative lesions (FHPL), including hyperplastic foci, hepatocellular adenomas and carcinomas, were quantified by image analysis and stereology. DEHP significantly enhanced the mean volume and volume % of FHPL, including liver tumors, but not numbers of FHPL/liver. Hepatocyte LI was also not affected, at least as detected by the technique used, while FHPL had significantly increased LI (14.5-48.3) as compared with normal hepatocytes (0.5-2.4). This study provides some evidence that enhanced chronic cell replication in the kidney may not always be associated with renal carcinogenesis of tumor promotion, while tumor promotion in liver may be a consequence of increased DNA synthesis in initiated or focus cells rather than in nonproliferative parenchymal hepatocytes, which may not be target cells of some tumor promoters. PMID- 2097174 TI - The ontogenesis of skin and organ characteristics in the Syrian golden hamster. II. Body and organ weights as well as blood glucose and plasma insulin levels. AB - The ontogenesis of the organ weights of the liver, kidneys, adrenals, testes and ovaries as well as the blood glucose and plasma insulin levels were studied in a total of 464 golden hamsters of both sexes of the acromelanic white inbred strain Bio 1.5 and agouti coloured outbred strain Han:AURA. Familial and seasonal influences were excluded by means of randomisation (25 groups from 1-365 days of life). Body weight development was found to be sigmoid and showed significant differences in terms of age, sex, and strain. Liver and kidney weights developed in parallel. Here, too, strain differences (agoutis greater than acromelanics) were seen, and sex differences were observed in the case of the kidneys (females greater than males). The increased adrenal weight in male hamsters compared to females was in accordance with species- but not rodent-typical behaviour. Both the testes and ovarian weights varied considerably. Age as well as, in part, strain differences were seen in the case of the blood glucose and insulin levels. The continual development of body and organ weight could be explained in terms of physiological changes. PMID- 2097176 TI - Blood vessel endothelia of the cerebral white matter of rats exposed to hypoxia. Karyometric and cytophotometric evaluation. AB - Hypoxic hypoxia is used as one of the models for examining the unfavourable effect of oxygen deficit on the nervous system. Since some morphological studies concerning the effect of hypoxia on the central nervous system have given consideration to perivascular lesion zones and glia alterations in the white matter, the present evaluation of the effect of hypoxia has been directed to vascular endothelia of the white matter. Examinations were conducted on adult rats of the Wistar strain which were exposed to acute hypoxia by being placed in a gas mixture containing 2% O2 or to moderate hypoxia - in a gas mixture containing 7% O2. Experimental animals were sacrificed 4 and 24 h after hypoxia and 14 and 60 d after hypoxia. The behaviour of vascular endothelia after hypoxia was evaluated by karyometric and cytophotometric methods. The measurements show an edema of endothelial nuclei in capillaries of the cerebral white matter of the rat in the first 24 h after hypoxia accompanied by nuclear chromatin index alterations proportional to the intensity of hypoxia. The measurements of endothelial nuclei 14 and 60 d after hypoxia show a development of a degenerative process in these nuclei, manifested by their decreasing size and by nuclear chromatin concentration in their central parts. The morphometric and cytophotometric examinations point to long-term alterations induced by hypoxic hypoxia. PMID- 2097175 TI - Hemodynamically induced heart lesions in the dog after the administration of cardio-active substances. PMID- 2097177 TI - Interindividual comparability of blood glucose alterations after meals of complex carbohydrates. AB - Young male and female probands underwent an DGTT (oral glucose tolerance test) using a glucose load of 1 g/kg b.wt. The alterations in blood glucose levels were checked and plotted by a Biostator. A week later groups of those probands were fed an isocaloric meal of complex CH, namely either potatoes, noodles or white bread. The resulting BG curves were also checked by a Biostator. It turned out that: 1. the shapes of the BG curves after glucose load were not interindividually comparable. 2. there was neither a similarity of the shapes of the BG curves within the groups after any of the different CH levels. 3. But if one compares the shape of the BG curves after glucose load and after a meal of any of the complex CH of one and the same person, there is a striking similarity in those curve shapes. The differences between them lie just in the mostly lower BG values of the curves after CH meals compared with those after glucose load. 4. Therefore the resulting graph of both of those curves is in all observed cases a straight line with a probability better than 0.001, called OGTT-calibrating resulting graph. PMID- 2097178 TI - Leukemia L 1210 cells induce depletion of Lyt 2+ thymocytes. AB - The thymocytes were analyzed on the 7th day after i.p. inoculation of 10(6) leukemia L 1210 cells to syngeneic DBA/2 Wf mice. A three-fold decrease of the total number of thymocytes was found as well as 1.7-fold decrease of the per cent of thymocytes with Lyt 2+ phenotype, while the per cent of cells with phenotypes Thy 1.2+ and Lyt 1+ was unchanged. PMID- 2097179 TI - Cytochalasin B-induced depolymerization of F-actin in chick embryo fibroblasts is dependent on cell density and anchorage to substratum. AB - The effect of cytochalasin B on F-actin amount and organization was measured in chick embryo fibroblasts (CEF) grown on solid substratum at low density, at high density, and suspended in a fluid medium. It was found that: 1) Cytochalasin B induced decrease in F-actin content only in cells growing at low density, in density-inhibited or suspended cells cytochalasin B had no effect on F-actin amount. 2) In cells grown at low density F-actin filaments organized in stress fibers are more resistant to cytochalasin B than F-actin which is not organized in fibrils. In cell density-inhibited or suspended in a fluid medium F-actin filaments are insensitive to the action of cytochalasin B, although they are not organized in stress fibers. These results are interpreted to reflect the influence of contact reactions on treadmilling in F-actin filaments. PMID- 2097180 TI - Topography of oxytocinergic estradiol target neurons in the mouse hypothalamus. AB - Combined (3H) estradiol autoradiography and oxytocin immunocytochemistry were used in order to study co-localization of cytoplasmic oxytocin immunoreactivity and nuclear uptake of (3H) estradiol in the forebrain of adult ovariectomized mice. Labelling with (3H) estradiol was found in subpopulations of neurons that constitute between 10 to 40% of the oxytocinergic cells in the paraventricular nucleus, the supraoptic nucleus and the intersupraoptico-paraventricular islands. Oxytocinergic neurons in the septohypothalamic nucleus, the anterior commissural nucleus, the periventricular nucleus and the zona incerta only occasionally showed nuclear uptake of (3H) estradiol. The results indicate that oxytocinergic cell groups within the classical magnocellular nuclei have much higher numbers of estrogen receptors than the so called accessory oxytocin neurons. Oxytocinergic neuronal systems seem to constitute functionally heterogenous populations of cells, differently influenced by estradiol. PMID- 2097181 TI - Comparison of bone formed in transplants of isolated scapular and vertebral osteoblasts. AB - To compare the properties of osteoblasts from various endochondrilia bones, scapular and calvarial osteoblasts were intramuscularly transplanted in "sandwiches" made of devitalized calvarial vaults. The structure of transplants produced by both types of bone cells appeared similar. In 4 week-old transplants woven bone with numerous osteoclasts predominated. The area occupied on the cross sections of transplants by bone tissue was considerably larger than that of the bone marrow cavities. Transplants of 8-week-duration contained mainly cancellous bone, the number of osteoblasts was low and the area taken by medullary space was larger than that of bone tissue. This finding indicates that either osteoblasts from various endochondrlia bones have similar properties or that the possible differences in intrinsic features of these osteoblasts were masked by the conditions of transplantation. PMID- 2097182 TI - Intraperitoneal injection induces prostaglandin-mediated protection from bile acid intestinal mucosal injury in rats in vivo. AB - The production of endogenous prostaglandins by the gastrointestinal mucosa can be induced by many processes. Whether the commonly used technique of intraperitoneal injection alone can also induce significant endogenous prostaglandin-mediated mucosal injury induced in vivo by perfusion for 45 min with 5 mM chenodeoxycholic acid. 10 control rats received 1 ml/kg of normal saline subcutaneously on abdomen tree hours before exposure to chenodeoxycholic acid. Another group of 10 rats received 1 ml/kg of saline intraperitoneally before injury. Mucosal injury was assessed histologically by measuring villus tip epithelial cell denudation by computerized quantitative morphology. Injury was assessed functionally by measuring water and mannitol absorption from the lumen. To examine the role of endogenous prostaglandins in this phenomenon, the above experiment was repeated with 10 and 12 rats respectively by replacing the saline with 10 mg/kg injections of indomethacin. Intraperitoneal injection of saline reduced the average denudation/villus caused by chenodeoxycholic acid: Subcutaneous = 100.8 microns +/- 14.7 (SEM). Intraperitoneal = 65.1 +/- 6.4 (p less than 0.5). Parallel reductions were noted in the increase in water secretion and mannitol absorption caused by chenodeoxycholic acid. All of these differences were reversed by exchanging indomethacin for saline. This study suggests there exists a mechanism by which the simple act of performing an intraperitoneal injection induces endogenous intestinal mucosal protection. That this protection is negated by pretreatment with indomethacin suggests it is prostaglandin mediated. PMID- 2097183 TI - Effects of aluminum on erythroidal cells in bone marrow in rats. AB - The study has been carried out on Wistar rats. The aim of the present study was to trace the effect of aluminum on erythroidal cells in bone marrow in rats. The number of proerythroblast after 10 days of experiment with aluminum slowly decreased up to 80 days of experiments. However, the number of basophilic erythroblasts after 10 days insignificantly increased but after 20 days gradually decreased up to 80 days of experiments. The bone marrow polichromatic erythroblasts after 10 days of experiment slightly decreased, however after 20, 40 and 80 days of experiments the values decreased significantly. The quality of orthochromatic erythroblasts after 10 days of experiments dropped and after 20, 40 and 80 days of experiments significantly decreased compared to the control value. Aluminum also brings about histological changes in the bone marrow. The statistical significant reductions of hemoglobin and hematocrit levels were found in the aluminum exposed rats. PMID- 2097184 TI - Stereological studies on the ultrastructural markers of renal tubular transport during accelerations acting along the +Gz axis. AB - The study was carried out on rats. Electron micrographs of the kidney obtained under +Gz accelerations were analysed. Using stereological methods the estimation of ultrastructural markers of active transport (mitochondria energy state), and passive transport (intercellular spaces and basal infolded channels) was performed in the proximal and distal tubules. The results obtained indicated that during the actions of accelerations active tubular transport was impaired as reflected by a lowering of mitochondrial energy states (similar to condensed) in the proximal and distal tubules. Widening of intercellular spaces and basal infolded channels was also observed, which suggests fluid stasis and thus impairment of passive transport. PMID- 2097185 TI - Analysis of the cell cycle in the root meristem of Allium cepa under the influence of ledakrin. AB - The influence of a polish anticancer drug on the cell cycle using Allium test was studied. Methods of aceto-orcein squash slides, curve of labelled mitoses after 3H-thymidine incubation and cytophotometrics after Feulgen's reaction were employed. Ledakrin acts strongly antimitotically, but it does not block the cell cycle completely. The cytostatic activity of ledakrin results from its action on the interphase. The phases G1 and S are prolonged while M is unchanged after 6h incubation with ledakrin. During postincubation in water without ledakrin it was noted, at the beginning, that the mitotic activity decreases and it is brought about the lengthening of S and G2 phases. The duration of the cell cycle phases returns to the control level during further postincubation. The results of analysis of chromatin aberrations and the micronucleus test point to a mutagenic effect of ledakrin. PMID- 2097186 TI - [Mouth breathing child and his craniofacial development. 1]. PMID- 2097187 TI - [Individual cast posts for single anterior implants]. AB - The Authors utilized in order to replace anterior missing teeth osseointegrated implants provided with individual angled posts. These types of abutment are used to allow a good parallel situation between implants with different angulation and also between implants and proximal teeth. The head of this abutment is thread to receive the screw that allows the crown to be fastened. PMID- 2097188 TI - [Condensation of gutta percha after McSpadden]. AB - The Authors have studied the efficacy of the sealing effect of thermomechanical compaction of guttapercha according to McSpadden with an in vitro analysis on undecalcified tooth sections and with a clinical evaluation of ten patients with periapical lesions. The analysis of the results has shown a good sealing capacity of the McSpadden technique. PMID- 2097189 TI - [Glass-ionomer cements in Class V restorations]. AB - The aim of the present study was to evaluate the effect of two different techniques of glass-ionomer application on the marginal microleakage in Class V restorations. Two types of composite resins were also used. Nonretentive Class V cavities were prepared at the cementum enamel junction of human extracted third molars. Glass-ionomer cements were applied with a chamfer technique or as base in the floor of the cavity. After restoration, the samples were stored in dye solution, sectioned and observed under optical stereomicroscope. The base technique for glass-ionomer cements showed less microleakage than the other restorative methods. PMID- 2097190 TI - [Severe tooth agenesis. Presentation of a case]. AB - In the present work the Authors describe a case of a patient affected by Duchenne disease as well as by dental multiple agenesis. It is a particular case of such rare syndromes in the same subject. PMID- 2097191 TI - [Training and professional profile of dentistry in the EEC. 9]. PMID- 2097192 TI - [Implantology in the USA--Technique of a restoration]. PMID- 2097193 TI - [Acrylic denture in the partially edentulous arch]. PMID- 2097194 TI - [Advantages and risks of composite inlays]. PMID- 2097195 TI - [Fixator--no substitute for the articulator]. PMID- 2097196 TI - [Modified inlay bridge--division with hinged attachment]. PMID- 2097197 TI - [Sequelae to Gysi Prize '90. Report of two participants]. PMID- 2097198 TI - [Modern occlusal surface--a synthesis of form and function]. PMID- 2097199 TI - [Thoughts on the total prosthesis]. PMID- 2097200 TI - [Full ceramic restorations of Optec HSP]. PMID- 2097201 TI - [Experiences with one housekeeping system]. PMID- 2097202 TI - [Esthetics and function of a prosthetic rehabilitation]. PMID- 2097203 TI - [Manufacture of an inlay bridge--fixing of unsuspended pontics]. PMID- 2097204 TI - [Bond strength of the biopaque system--testing of various alloys]. PMID- 2097205 TI - [Materials science analysis of the uses of the SR-Ivocap polymerization system]. PMID- 2097206 TI - [Silicoater increases bonding strength in the adhesive technique]. PMID- 2097207 TI - [Conus-connector-system. Stress-free connection to the secondary part]. PMID- 2097208 TI - [Mrs. B. is fitted with a full denture]. PMID- 2097210 TI - [Achievable esthetics in the daily work practice]. PMID- 2097209 TI - [Variation in full ceramic restorations--possibilities and seeming impossibilities]. PMID- 2097211 TI - [Abrasion resistance of dental veneering materials]. PMID- 2097212 TI - [Dental screw systems--New tool kit simplifies the process]. PMID- 2097213 TI - [Sore spots on the denture base--causes; effects and their prevention]. PMID- 2097214 TI - [Fixed-removable tooth replacement combined with precision "APS-T-attachments" (Degussa)]. PMID- 2097215 TI - [Surface improvement coatings--an alternative to the titanium casting technique?]. PMID- 2097216 TI - [Mrs. B. is fitted with a new denture]. PMID- 2097217 TI - [In-Ceram: unexpected progress in the metal-free ceramic technique]. PMID- 2097218 TI - ["SG" attachment by Degussa. An advance of the pin-attachment?]. PMID- 2097219 TI - [Application of computer-assisted occlusal diagnosis]. PMID- 2097220 TI - [Manufacture of sintered tooth replacements--the first clinical results]. PMID- 2097221 TI - [Conceptual manufacture of an inlay-onlay partial restoration]. PMID- 2097222 TI - Radiographic study of structural changes in the temporomandibular joint after oblique sliding osteotomy: comparison between the extra-oral and intra-oral approaches. AB - Oblique sliding osteotomy of the mandibular rami was performed on 41 patients by either an intra-oral (21 patients) or extra-oral (20 patients) approach. The temporomandibular joints were radiographed preoperatively and then immediately and 18 months postoperatively. Signs of structural changes were recorded so as to compare the two approaches to osteotomy. The most common findings following the operation were signs of sclerosis and bone remodelling in 85% and 73% respectively of the two groups but these differences were not statistically significant. PMID- 2097223 TI - Analysis of the diagnostic process in sialography. AB - The diagnostic process in sialography was evaluated using the mouse parotid gland as a model. The relative significance of each of the three diagnostic phases, psychophysical, psychological and nosological, was determined by analysing observer accuracy in detecting sialoadenitis and sialodochitis on digital and analogue microsialograms. Automated diagnosis based on parametric values of the digitized image was compared with the human system using ROC analysis. The overall accuracy of automated diagnosis was superior to that of an observer with analogue images. It is concluded that if observers were to be given the same quantitative information and informed of its diagnostic value in the psychological phase, then variation in the detection of the abnormalities could be reduced and the overall diagnostic accuracy in sialography improved. PMID- 2097224 TI - Influence of different developing solutions and developing times on radiographic caries diagnosis. AB - One hundred extracted premolars were radiographed under standardized conditions with D- and E-speed films. The films were developed with conventional and rapid processors using varying developing times. The influence of different developers and developing times on the diagnostic accuracy of radiographic caries diagnosis was evaluated with the aid of ROC technique. Rapid processing using the developing time recommended by the manufacturer led to a lower density and contrast compared with the conventional developer. Underdeveloped films using the rapid processors resulted in an unacceptable low level of diagnostic accuracy, but otherwise it was the same for all developers, developing times and both types of film. PMID- 2097225 TI - Computerized generation of lesion models for evaluating subtraction radiography. AB - Digital subtraction radiography is a technique that has been shown to provide greater sensitivity and specificity in detecting bur-induced crestal bone change than the traditional comparison of two radiographs. It is questionable, however, to what extent these reports relate to clinical situations. A computerized method of extracting lesion areas from clinical subtraction images and imposing them on radiographs of experimental sites has been developed with the goal of producing a more relevant model for evaluating subtraction radiography. Observers were unable to distinguish between natural lesions and those produced by this method. PMID- 2097226 TI - Ultrasound diagnosis of lymph node metastasis in head and neck cancer. AB - The role of ultrasonic (US) examination in the detection of cervical lymph node metastasis from head and neck cancer has been evaluated. The subjects were 57 patients with carcinoma of the oral cavity, maxillary sinus or oropharynx who underwent radical neck dissection. The preoperative US and postoperative histopathological findings were compared in 181 lymph nodes (LNs) of 5 mm or more in diameter. LNs were evaluated by US with reference to their size, shape, boundary and internal echoes. The histologically positive rate was higher for larger LNs on US scans: 96% (44/46) of LNs of 15 mm or more were positive. On the other hand, 95% (18/19) of the flat LNs were negative. The positive rate was higher for well delineated than poorly delineated LNs, but similar among the homogeneous, heterogeneous and reflective core patterns of internal echoes. No LNs were detected by US in six of the 57 patients, of which four were true negative and the other two false negative. In the two false negative patients, histopathological examination showed a total of four LNs with two showing extensive extranodal spread of tumour and fibrosis of the surrounding tissue due to previous radiotherapy. Whether LNs are metastatic or not is difficult to determine directly by US. However, the positive rate can be enhanced by evaluation of the size, shape and boundary of the LN. US is indispensable for diagnosing cervical lymph node metastasis in patients with malignant head and neck tumours. PMID- 2097227 TI - The synchondrosis between the greater horn and the body of the hyoid bone: a radiological assessment. AB - The synchondrosis between the greater horn and the body of the hyoid presents as a vertical radiolucent line, which may be mistaken for a fracture. The incidence of its presence on dental radiographs was assessed in two age groups. Since it is a normal feature in many hyoid bones, especially in the younger age group, it is important to identify it as such. PMID- 2097228 TI - Parameters affecting radiographic contrast. AB - Kilovoltage, in most cases a variable readily controlled by the operator, and half-value layer have come to be regarded as factors defining image contrast. This has led to the assumption that comparable levels of image contrast may be obtained using X-ray units operated at the same kilovoltage and with the same half-value layer. To ascertain the validity of this view X-ray beams generated by seven X-ray units were compared with each other and with those from a Gendex Model 1000 operated at the same kilovoltage. The basis for comparison was the level of image contrast the X-ray beams were capable of producing after passage through selected thicknesses of aluminium absorber. While results showed no correlation between the nominal (stated) operating kilovoltage of any X-ray generator studied and the level of image contrast produced, a correlation (-0.98) was found between the measured half-value layer and image contrast when the units tested were compared with the Model 1000. This information should significantly affect the criteria used for the selection and/or operation of X-ray generators. PMID- 2097229 TI - Mucous cyst of the sphenoid sinus. AB - Sphenoid sinus mucous cysts are rare, benign, expansile masses, which can form mucoceles if the entire sinus is filled. Due to their close proximity to numerous important anatomical structures, they can cause a variety of different symptoms. The incidental finding of a sphenoid sinus mucous cyst during cephalometric radiology for orthodontic analysis is reported. PMID- 2097230 TI - Basal cell carcinoma syndrome: report of 10 cases. AB - Ten cases of basal cell carcinoma syndrome are presented. The jaw cysts were proved histopathologically to be odontogenic keratocysts. The multiple naevoid lesions on the skin were identified as basal cell carcinoma in two cases. Skeletal anomalies and intracranial calcification were present in all cases. A positive family history with others affected by the syndrome was traced in two cases. PMID- 2097231 TI - Principles of forensic dentistry: 1. Identification procedures. AB - From time to time the general dental practitioner may become involved in forensic cases, when he or she will need to be aware of the general principles involved and the increasing variety of modern techniques available. This two-part article reviews those principles and techniques. In Part 1 procedures used in identifying bodies are discussed. Part 2 will concentrate on non-accidental injury to children and analysis of bite marks, and discuss archaeological investigations. PMID- 2097232 TI - Night guards and occlusal splints. AB - Occlusal splints/night guards can be an effective, inexpensive and reversible treatment for a wide range of dental problems. The author describes their clinical uses, discusses some of the rationales that have been given for these uses, and outlines the designs that have the widest clinical application. PMID- 2097233 TI - Chemical control of plaque. AB - Plaque is generally accepted as the prime agent in the aetiology of gingivitis and caries. However, it has been estimated that the oral microbial load must be reduced by some 99.9% in order to produce a significant effect on plaque formation--and mechanical tooth cleaning alone is unlikely to achieve this. Considerable effort has therefore been put into researching chemical means of controlling plaque. In the final article of this eight-part series, the author reviews the efficacy and modes of action of the chemical agents currently available. PMID- 2097235 TI - Intravenous sedation and patient response to minor oral surgery--experience of 408 cases. AB - This article presents the results of a patient questionnaire on response to minor oral surgery carried out under local anaesthetic and intravenous sedation. The predominantly favourable response of the respondents leads the author to suggest the use of IV sedation as a means of reducing patient anxiety, and so increasing dental attendance. PMID- 2097234 TI - Root canal retained restorations: 3. Root-face attachments. AB - It has been common practice for many years to use retained roots to provide support and stability for partial or full dentures. The retention of such overdentures is greatly enhanced if the remaining roots are modified and restored with posts and root-face attachments. The final article in this series on root canal retained restorations classifies and describes some of the root-face attachments currently available, and also describes a number of prefabricated post systems with integral overdenture attachments. Guidelines for clinical and laboratory procedures are given. PMID- 2097236 TI - Congenital epulis interfering with feeding in a day-old baby girl. PMID- 2097237 TI - Professional negligence in dentistry. AB - Society is becoming more litigious, and dentistry has not been exempt. However, by following correct and prudent professional procedures at all times, dentists may sensibly expect to avoid serious litigation. In the first of an irregular series on dento-legal topics, Bernard Smith reviews the thorny subject of negligence in dentistry, and gives advice on both how to prevent and how to respond to accusations. Other articles in the series will look at particular legal problems in the dental specialties. PMID- 2097238 TI - Cermet--an ideal core material for posterior teeth? AB - Both amalgam and composite have limitations as core materials. Cermet cements, with their ease of preparation and placement, cariostatic effect, and adhesion to tooth substance, have some advantages over both of these commonly used materials. This article reviews the suitability of glass-ionomer/cermets for use in building up cores on posterior teeth, and provides a guide to the clinical technique. PMID- 2097239 TI - Understanding pathologists (an exercise in communication): 1. Understanding pathology. AB - Pathology is a discipline that is often approached with some reserve by nonpathologists. In this four-part series the author aims to 'demystify' the subject. The objective of this first article is to improve understanding of the purposes, limitations and methodology of pathology. In essence the role of the diagnostic histopathologist is to help the clinician help the patient. If, in the request for help, the clinician states clearly why a histological examination is required and gives a relevant history, the pathologist finds it much easier to return a useful report. The subsequent three articles in this series will look in some detail at biopsy techniques, the pathologist's report and special laboratory investigations. PMID- 2097240 TI - Principles of forensic dentistry: 2. Non-accidental injury, bite marks and archaeology. AB - From time to time the general dental practitioner may become involved in forensic cases, when he or she will need to be aware of the general principles involved and the increasing variety of modern techniques available. This two-part article reviews those principles and techniques. In Part 1 the principal procedures used in identifying bodies were discussed. Part 2 now reviews the role of the forensic dentist with respect to non-accidental injury to children, analysis of bite marks, and archaeological investigations. PMID- 2097241 TI - Gray translucent teeth. PMID- 2097243 TI - Fit failures of dental laboratory castings. PMID- 2097242 TI - Oral surgical complication. PMID- 2097244 TI - Association between cigarette smoking and the prevalence of dental caries in adult males. PMID- 2097245 TI - Simplified approach to dental statistics. PMID- 2097246 TI - Evolving pattern of dental practice. PMID- 2097247 TI - Comparative radiopacity of intermediary bases. PMID- 2097248 TI - Use of glass ionomer cements by Iowa dentists. PMID- 2097249 TI - Anodontia and jaw dysplasia syndrome: an isolated, idiopathic aberration. PMID- 2097250 TI - Incisal rest extrusion bar. PMID- 2097251 TI - Journal of functional orthodontics interviews Dr. Brendan Stack on TMJ. Interview by Dr. Jimi Mehta. PMID- 2097252 TI - Use of powerful small magnets to achieve rapid tooth movement. PMID- 2097253 TI - Case report by Dr. Sang Duk Lee. Treatment of Class III malocclusion by sagittal appliance and fixed appliance. PMID- 2097254 TI - Role of trigger points in the management of head, neck, and face pain. PMID- 2097255 TI - Simple solution to open-bite treatment: elastodontics. PMID- 2097257 TI - Adult orthodontic and TMJ retreatment with elastodontic appliance. An early progress report. PMID- 2097256 TI - Case report: Shane Holcome. PMID- 2097258 TI - Lynn Magnathologic Corrector. AB - The Lynn Magnathologic Corrector is an orthopedic mechanical and magnetic traction device designed to enhance the concepts of the Bio-Finisher. Dr. Lynn invented the Bio-Finisher to eliminate the problem of not achieving adequate vertical alveolar (osseous) and dental support for the neuromuscular tissue operating system. The Lynn Magnathologic Corrector is an evolutionary advance in both performance and convenience for the doctor and the patient. PMID- 2097259 TI - Immunophenotypic, cytogenetic and molecular investigations in two cases of CALLA positive acute myeloid leukemia. AB - Clinicopathological and cytogenetic features of two patients with acute myelogenous leukemia (AML) whose blast cells coexpressed myeloid-associated antigens and CALLA are described. Leukemia cells revealed myelomonocytic (FAB-M4) and monocytic (FAB-M5) features, while the nonblast cell population exhibited trilineage myelodysplasia in both cases, a finding suggestive of multiple-cell lineage involvement. Cytogenetically, a deletion of the long arm of chromosome 6 was found in one patient, and normal metaphases were detected in the other. Molecular studies disclosed a rearrangement of the IgH locus in one patient. Clinically, these patients were unresponsive to antimyeloid regimens including Daunorubicin and Cytarabine, two agents normally also effective on lymphoblastic leukemias, possibly indicating the need for alternative protocols for the treatment of CALLA positive AML. PMID- 2097260 TI - Comparative evaluation of differential leukocyte counts by Coulter VCS cytometer and direct microscopic observation. AB - Comparative analyses of the leukocyte differential counting were performed using a Coulter VCS Hematology Flow Cytometer and direct microscopic observation on 547 unselected individuals analyzed at the outpatient clinic of the Institute of Hematology "L. e A. Seragnoli" of Bologna. The Coulter VCS is able to provide leukocyte differential counting by measuring cell volume, conductivity and laser light scatter. Negative (true negative: 50.8%) results were observed in 278 subjects by both automated and direct observation methods. Abnormal cells in the blood samples (true positive results) were detected both by VCS and by direct observation in 199 cases (36.4%). Regional distribution of the cells in specific "flags" on the scatterplot was often associated with specific cell types. In 66 cases (12.1%) no abnormal cell was detected by direct observation, while Coulter VCS gave an abnormal pattern, even if only to a slight extent (false positive cases). In 4 cases only (0.7%), false negative results were given by the VCS system. The correlation of the results given by the VCS system with those given by direct microscopic analysis was very high; however careful control by the operator was essential in evaluating the data given by the automated system and in identifying the type of abnormal cells detected. PMID- 2097261 TI - Factors leading to the appearance, after BMT, of cytotoxic antibodies against T, B and activated T lymphocytes: critical appraisal. AB - In order to investigate the role of lymphocytotoxic antibodies, acquired after allogeneic and autologus bone marrow transplantation, we studied 309 sera from 42 transplanted patients (16 adults and 26 children). We tried to correlate antibody elicitation towards T, B and activated T lymphocytes with the following parameters: genetic (recipient's and donor's sex, HLA profile), clinical (recipient's primary disease, GvHD, transplant outcome) and technical (bone marrow purging, auto-or allotransplant). There is evidence that anti-T and -B cytotoxic antibodies appear earlier than anti-activated T antibodies. Anti-HLA specific antibodies seem to be produced by the transfusional stimulus: they appear early after BMT and wane after the first year. Humoral responsiveness seems to be age related (adults are more responsive than children) and conditioned by GvHD (the level of cytotoxic antibodies decreases when GvHD is prevented by bone marrow purging). The level of cytotoxicity is significantly lower in the sera of autotransplanted patients compared with the allotransplanted ones. It appears that anti-activated T antibodies are produced by cell activation at different times in adults and children: in adults this occurs during GVHD and in children during the relapse of disease. PMID- 2097262 TI - Haematologic abnormalities in the acquired immunodeficiency syndrome. AB - During the clinical history of HIV infection, haematological abnormalities represent a common finding which not only contributes to worsening the clinical condition but also limit the use of antibacterial as well as antiviral agents. On the basis of the regulatory role played by the immune system on haemopoiesis, in the present review the foremost derangements of the immunoregulatory circuits are first discussed. The main functional and quantitative defects of peripheral blood erythrocytes, granulocytes, platelets and monocytes are then analysed, and the different bone marrow pictures observed during the progression of the disease are described. To elucidate the physiophatogenetic mechanisms responsible for bone marrow and peripheral cytopenia, the most relevant in vitro studies are reported and discussed. These studies suggest that both a direct cytopathic effect of HIV on haemopoietic progenitors and an immune system mediated mechanism are involved. In view of the HIV selective tropism for lymphocytes and macrophages, which are a major source of haemopoietic growth factors, the new therapeutical strategies for the treatment of cytopenias based on exogenous administration of these cytokines, alone or in combination with antiviral drugs, are briefly reported. PMID- 2097264 TI - Cold agglutinin hemolytic anemia in a patient with adult-onset Still's disease. AB - We report on a patient with adult Still's disease who developed, at the onset of her illness, an autoimmune hemolytic anemia (AHA) due to cold agglutinin (CA). Hemolysis spontaneously subsided and CA disappeared before starting therapy with aspirin and prednisone. The occurrence of AHA in patients affected with collagen diseases is currently explained by a loss of tolerance, leading to the emergence of multiple autoreactive clones. In our case the self-limiting course of AHA leads us to propose another interpretation, i.e. that the cold reactive autoantibody might have been related to a transient infection able to play a pathogenetic role in the systemic disease, as suggested by several authors. PMID- 2097265 TI - Unicentric Castleman's lymphadenopathy presenting with Behcet's syndrome: a case report. AB - We describe a male patient with Behcet's syndrome and Castleman's lymphadenopathy. He was affected by severe oral and genital ulcers, bilateral uveitis, necrotic purulent nodules on both hands. A CT scan of the mediastinum showed the presence of a mediastinal mass. On the basis of histological and immunohistological findings, a diagnosis of Castleman's disease, angiofollicular type, was formulated. The lymphadenopathy was unicentric. After the surgical excision of the mediastinal mass (January, 1989) until now, Behcet's syndrome is in complete remission with a low dosage of prednisone. PMID- 2097263 TI - Unusual sickle cell disease observed for the first time in Italy: Hb S-Hb D Los Angeles. AB - In Italy sickle cell disease is mainly represented by sickle cell anemia (beta s/beta s) and sickle cell thalassemia (beta s/beta oth or beta s/beta+ th). Association of Hb S with other beta variants has been observed in other ethnic groups. Since some of these variants have electrophoretic mobility at alkaline pH similar to Hb S, they are frequently misinterpreted as Hb S in the homozygote state. This paper reports the first case of Hb S/Hb D-Los Angeles observed in Italy. The authors underline the need to perform accurate and specific tests in all patients with sickle cell disease and available relatives, in order to exclude combinations of Hb S with other beta hemoglobin variants. PMID- 2097266 TI - Chronic myelogenous leukemia following radiotherapy and chemotherapy for non Hodgkin lymphoma. AB - We report here a women who developed chronic myelogenous leukemia (CML) after successful radiotherapy and chemotherapy for non-Hodgkin lymphoma. Review of the literature indicates that exposure to ionizing radiation is associated with an increased risk of CML. PMID- 2097268 TI - Prognosis in Hodgkin's disease: verification of a new predictive equation. PMID- 2097267 TI - An unusual case of Candida tropicalis sepsis in a patient submitted to allogeneic bone marrow transplantation. AB - We describe an exceptional case of Candida tropicalis sepsis in a patient submitted to allogeneic BMT; the diagnosis was made on a peripheral blood smear, when the pt was neutropenic and only mildly febrile. The combination of GM-CSF to accelerate hematological recovery and the possibility of administering large doses of a liposomal form of Amphotericin B were the contributing factors to the resolution of the infection. PMID- 2097269 TI - Carcinoma of Vater's papilla in patient affected by multiple myeloma. PMID- 2097270 TI - Effects of interferon and 5-methylthioadenosine on HL60 cell line proliferation. PMID- 2097271 TI - Thalassemia intermedia and recurrent priapism following splenectomy. PMID- 2097272 TI - Urateoxidase in severe hyperuricemia during acute renal failure after heart transplantation. PMID- 2097273 TI - Simultaneous occurrence of larynx carcinoma and acute blastic transformation in a patient with essential thrombocythemia. PMID- 2097274 TI - Apparent maternal exclusion due to Duffy phenotypes. PMID- 2097275 TI - 1,25-Dihydroxyvitamin D3 administration in a case of hairy cell leukemia. PMID- 2097276 TI - Serum C-reactive protein and infections in malignant hematological disorders. PMID- 2097277 TI - [Use of monoclonal antibodies for studying cytochrome P-450 forms. Use of interspecies homology of amino acid sequence]. AB - The current research on utilization of monoclonal antibodies for isolation of cytochrome P-450 forms, substrate specificity determination, localization in tissues and contribution in DNA adduct formation is reviewed in this paper. Usefulness of monoclonal antibodies directed against rodent cytochrome P-450 isoenzymes to human investigations is emphasized. PMID- 2097279 TI - [Effect of monoclonal antibody against methylcholanthrene-induced cytochrome P 450 forms on benzo(a)pyrene metabolism in hepatic microsomes of C57BL/10 mice]. AB - In this study, hepatic microsomes from 5,6-benzoflavone induced C57BL/10 mice were used. To inhibit monooxygenase activities, the monoclonal antibody MAb 1-7-1 recognizing two isoenzymes of methylcholanthrene-induced cytochrome P-450 was applied. Microsomes were incubated with tritium labeled benzo(a)pyrene [G-3H]BP for 10 min at 37 degrees C. The incubation mixture contained: 50 mM potassium phosphate buffer, pH 7.25; 30 mM KCl; 3 mM MgCl2; 2 mM NADPH; 80 microM [G-3H]BP (specific activity 50 mCi/mmol); and monoclonal antibody MAb 1-7-1 or ascites fluid (NBS) containing nonspecific IgG as a control. The ratio of antibody protein/microsomal protein was 2:5. BP metabolites were extracted from incubation mixtures by ethyl acetate. The organic layer was dried over sodium sulfate, and evaporated under a stream of nitrogen. To separate BP metabolites HPLC technology was used. The column was eluted with methanol gradient (60-100%) for 45 minutes. The radio-activity of collected samples was determined using liquid scintillation counter. Differential inhibitory effects of MAb 1-7-1 on BP-metabolites formation were found, e.g. 7,8-diol was inhibited by 86.1% and quinones by 62.5%. The predominant metabolite, 3-OH-BP, was inhibited by 80.4%. Moreover, it was found that MAb 1-7-1 inhibition of benzo(a)pyrene hydroxylase activity (by 75.8%, as measured by fluorescent technique) was very similar to the inhibition of 3-OH-BP along with 9-OH-BP formation (as measured by HPLC). PMID- 2097280 TI - [Effects of age and selected inductors of aromatic hydrocarbon hydroxylase (AHH) activity in the rat liver]. AB - The effects of treatment with phenobarbital, beta-naphthoflavone and dexamethasone on 0,5, 1, 2, 4, 8, 12, 20 and 28 month old male Wistar rats was studied. The animals were treated intraperitoneally with phenobarbital (50 mg/kg; two times), beta-naphthoflavone (20 mg/kg; three times) or dexamethasone (10 mg/kg; three times). The rats were killed and Dallner method hepatic microsomes were isolated. In this fractions the protein by Lowry method and AHH activity according to Gelboin were determined. The AHH activity changes was not observed with age. In all studied animals (with 28 months old rats) phenobarbital inhibited AHH activity. The beta-naphthoflavone markedly increased the AHH activity; particularly in sex maturation and senescent. The dexamethasone injections also increased activity of the enzyme but in young rats only. PMID- 2097278 TI - [Benzo(a)pyrene metabolism in human fibroblasts--effect of 7,8-benzoflavone]. AB - Benzo(a)pyrene (BP) metabolism was studied in cultured fibroblasts from healthy donor. Cells were cultured in Eagle medium supplemented with 10% fetal calf serum, 2 mM 1-glutamine, 100 U/ml penicillin and 100 micrograms/ml streptomycin. Cultures were grown at 37 degrees C to confluence in 45 cm2 culture flasks containing 15 ml medium and refed with fresh medium 24 h prior to treatment with BP. Cells were treated for 24 h with [G-3H]BP diluted with BP to give a final concentration 10 microM and a specific activity of 0.3 Ci/mmol. The metabolites were extracted by ethyl acetate, dried with Na2SO4, evaporated with nitrogen and injected into high pressure liquid chromatograph. The column (LiChrosorb RP 18) was eluted with a linear gradient of 60% methanol in water to 100% methanol in 45 min at a flow rate 0.8 ml/min. Radioactivity of fractions was measured. Following metabolites were identified: 3-hydroxy-BP (23.7%), 9-hydroxy-BP (17.0%), quinones (22.9%), 7,8-dihydroxy-BP (6.1%), 9,10-dihydroxy-BP and other derivatives (30.3%). 7,8-benzoflavone--an inhibitor of BP hydroxylase and epoxide hydrase, strongly inhibited the metabolism of BP in human fibroblasts, changing the proportions in the amounts of the metabolites. The ratio of phenols to the other metabolites increased twice under the influence of 7,8-benzoflavone. This suggests that 7,8-benzoflavone has the stronger inhibitory effect on epoxide and diol formation in comparison with BP hydroxylation. PMID- 2097281 TI - [Evaluation of the inducing and autoinducing properties of pyrene, fluoranthene and benz(a)anthracene]. AB - In the present study we have examined the effect of treatment with benz(a) anthracene (BaA), pyrene (P) and fluoranthene (Fl) on the total liver microsomal content of cytochrome P-450 and elimination of these PAH from blood in rats. The experiment was carried out on adult male rats Wistar breed. Oil solution of inducers: benz(a)anthracene, pyrene and fluoranthene in dose 20 mg/kg were administered individually one or threefold by gavage. 24 h after a single dose of PAH cytochrome P-450 content in rat liver determined by the method of Omura and Sato was the same as in control group. When PAH were administered p.o. for three consecutive days in the fourth day of experiment cytochrome P-450 content was increased from about 0.68 nM/mg protein to about 1.2 nM/mg. Since the increase of cytochrome P-450 may influence on elimination of xenobiotics we have determined affect PAH on their blood level after i.v. administration. One hour after BaA administration and two hours after Fl and P blood samples were collected. Concentration of PAH in blood was determined by gas-liquid chromatography. Pretreatment of rats with BaA decreased elimination of Fl, P, BaA from blood in comparison to the control rats. It indicated on the self-inducing effect of BaA on its own metabolism and inducing effect of metabolism other PAH. Pretreatment of rats with pyrene decreased elimination of BaA. It seemed that pyrene inhibited the oxidation of BaA in rat liver microsomes. PMID- 2097282 TI - [Specificity of cytochrome P-450 forms in the rat liver after inhalation of multicomponent hydrocarbon mixture]. AB - Rats were inhaled with C6-C9 petroleum fraction 12 hrs daily for 9 days. The hydrocarbons and their metabolites gas chromatographic profiles from liver, kidney, brain and blood were investigated by means of head space technique. The observed characteristic profile composed of some hydrocarbons and secondary alcohols does not undergo qualitative changes and internal quantitative proportions remain constant in spite of cytochrome P-450 induction. Only total amount of hydrocarbons and their metabolites was varied. The results suggest that C6-C9 petroleum fraction inhalation does not induce new forms of cytochrome P-450 with different catalytic properties, but at the same time substrate binding site is modified to facilitate biotransformation of hydrocarbons and their metabolites. PMID- 2097283 TI - [Spectral interactions of cytochrome P-450 with n-heptane and methanol]. AB - Methanol interacts with cytochrome P-450 to produce the reversed type I spectral change. In the presence of type I substrate n-heptane, the methanol induced spectrum disappears without detectable effects of interaction suggesting that methanol is a very weak ligand for heme iron of cytochrome P-450. Methanol strongly lowers the apparent spectral dissociation constant (Ks app) of n-heptane binding with rat liver cytochrome P-450 both in control and C6-C9 petroleum fraction inhaled group. In control group, titration of cytochrome P-450 with methanolic solutions of n-heptane does not change the maximal spectral interaction (Amax) observed with pure n-heptane. However in the inhaled group during titration of induced cytochrome P-450 with methanolic solutions of n heptane an additional type I spectral change is observed. Thus addition of "equivalent" amounts of methanol into the reference cuvette during titration with methanolic solutions overestimates the true magnitude of type I spectral change of cytochrome P-450 with n-heptane. PMID- 2097284 TI - [Induction of cytochrome P-450 monooxygenase after combined exposure of rats to xylene and ethanol]. AB - Increased biological risk following from combined exposure to xylene, an industrial solvent, and ethanol, the most likely additional factor to occupational exposure, may result from inductive effects of the chemicals on cyt. P-450 monooxygenase, where biotransformation of xylene and, in part of ethanol, takes place. Studies were carried out on rats: 1) preinduced with ethanol (10% solution in drinking water for 8 months) and for next 9 days jointly exposed to xylene vapour at concentration of 12,000 mg/m3; 2) preexposed to m-xylene vapours at concentration of 4,000 mg/m3 for 6 and 12 weeks or at concentration of 400 mg/m3 for 5 months and for next 3 days jointly administered ethanol (5 doses of 2.5 g/kg in 12 hours intervals). It has been found that ethanol and xylene in both models of combined exposure exert additive stimulatory effects on the activity of cyt. P-450 monooxygenases (aniline p-hydroxylase, microsomal ethanol oxidizing system, NADPH-cyt. c reductase, cytochrome P-450) and intenseness of the effects depends both on the level and duration of exposure to xylene/m-xylene and ethanol. PMID- 2097285 TI - [Stimulation of microsomal lipid peroxidation as the effect of combined action of xylene and ethanol]. AB - The aim of the study was to evaluate if in the case of combined exposure of rats to xylene and ethanol stimulation of lipid peroxidation in the liver microsomes (an index of interaction with lipids and derangements of integrity/fluidity of membranes) might occur. Experiments were carried out on male Wistar rats in the conditions of prolonged, inhalatory preexposure to m-xylene at concentration of 4000 mg/m3 for 6 and 12 weeks, and next joint 5-fold treatment with ethanol (2.5 g/kg oral doses in 12 hours intervals for 3 days). The degree of lipid peroxidation was assessed both in vivo and in vitro under chemical stimulation: enzymatically (NADPH, Fe2+) and nonenzymatically (ascorbic acid, Fe2+). The chemical stimulation permits to measure multiplied biological effects of chemicals acting in vivo. As a results of performed studies it was found that the highest increase of lipid peroxidation appeared in the case of prolonged, 12 weeks exposure to m-xylene (4000 mg/m3) and successively under subacute ethanol treatment and 6-week m-xylene exposure. Thus, it was evidenced that stimulation of lipid peroxidation depends on the duration of exposure to m-xylene. Stimulation of lipid peroxidation, revealed here, may arise from the processes of biotransformation of xylene in cyt. P-450 monooxygenase system where generated oxygen free radicals may attack the lipid components of microsomal membrane as well as from the mechanisms leading to decrease of antioxidant ability of the organism (decrease of glutathione-SH and vitamins E and C levels). PMID- 2097286 TI - [Evaluation of the inducing action of aroclor 1254 in rats in long-term experiment]. AB - The pharmacokinetics of antipyrine in a dose of 20 mg/kg i.v. and cytochrome P 450 level in liver, were studied in control and pretreated rats with 1, 5, 25 ppm polychlorinated biphenyls in food for up to 120 days. The objective of this work was to quantitate the effects of low environmental levels of the contaminant and enzyme inducer (PCB) on the pharmacokinetics of antipyrine, a drug whose primary elimination route is liver metabolism. After 30 days of pretreatment only the 25 ppm treated rats showed any significant acceleration of antipyrine elimination. At the 60 and 120 days samplings, both the 5 and 25 ppm pretreatments show significant acceleration of antipyrine elimination. The changes in cytochrome P 450 lever were similar and no significant effects on body weight and volume of distribution was observed. PMID- 2097287 TI - [Benzodiazepines as cytochrome P-450 and cytochrome b5 inductors in rat liver microsomes]. AB - Among the benzodiazepines tested (diazepam, oxazepam, clonazepam, nitrazepam and chlordiazepoxide ) chlordiazepoxide is the most potent inducer of cytochrome P 450, diazepam is a poor inducer, whereas clonazepam and nitrazepam do not possess a capacity to induce of cytochrome P-450. On the other hand, microsomal cytochrome b5 is induced by diazepam only. The extent of induction of cytochrome P-450 and cytochrome b5 depends on the environmental temperature. Chlordiazepoxide is the most potent inducer of cytochrome P-450 in rats exposed to an ambient temperature of 28 degrees C, whereas diazepam have the highest induction ability in rats exposed to 35 degrees C. On the other hand, nitrazepam increased the content of cytochrome b5 in rats exposed to temperature of 35 degrees C only; diazepam was the most potent inducer of cytochrome b5 in rats exposed to temperature of 21 degrees C. These results indicate that high ambient temperature is a factor modifying the ability of benzodiazepines to induce of microsomal cytochrome P-450 and cytochrome b5. PMID- 2097288 TI - [Structure and effects of benzodiazepines on hepatic microsomal monooxygenases in rats exposed to environmental temperature]. AB - Five benzodiazepines (diazepam, oxazepam, clonazepam, nitrazepam and chlordiazepoxide) were compared with respect to their capacity to affect microsomal aniline hydroxylase, aminopyrine N-demethylase and 4-nitroanisole O demethylase of rats exposed to the high ambient temperature of 28 degrees C or 35 degrees C. We have stated that the highest effect on the microsomal enzyme activities was observed after chlordiazepoxide, clonazepam or nitrazepam treatments. These results indicate that the presence of nitro group at position 7 or N-oxide at position 4 of benzodiazepine is important for the ability of benzodiazepines to affect the hepatic microsomal enzymes. High environmental temperature modifies the effect of benzodiazepines on tested microsomal enzymes. PMID- 2097289 TI - [Diurnal rhythm of phenacetin and antipyrine elimination in rats]. AB - Pharmacokinetic studies indicate the diurnal rhythmicity of metabolism of many drugs. Partially it is a result of circadian variations of mixed function oxidase system, which metabolizes some drugs. The aim of the experiment was to evaluate the elimination rate phenacetin and antipyrine in different periods of day under standard light/dark (L/D) conditions (08.00-20.00/20.00-08.00). Studies were carried out on rats intragastrically treated with phenacetin in a dose of 0.42 mmol per kilogram of body weight or antipyrine in a dose of 0.17 mmol/kg at 14.00, 20.00, 02.00, 08.00 and 14.00 o'clock. The rate constants (k) were calculated on the basis of concentration of both substances in blood 2 and 3 hours after administration. Excretion of p-aminophenol in urine was determined in mentioned hours after administration of phenacetin in a dose of 0.28 mmol/kg per os. Differences of rates of elimination of both drugs were found. The maximum occurred at 10.00, and minimum at 22.00 o'clock, which indicate circadian periodicity of metabolism. PMID- 2097290 TI - [Systemic localization of mixed function oxidases]. AB - The localization of cytochrome P-450 dependent monooxygenase system in particular organs as well as in cellular structures has been presented. Attention was paid to microsomal, mitochondrial (inner membrane), nuclear (nuclear envelope), nucleolar localization of the system. In the liver cytochrome P-450 dependent monooxygenases occur in their maximum concentration, clustering in hepatocytes of the III acini zones. Cytochrome P-450 contents and the activity of its reductase gradually decrease in cells of the II and I zones. In the nephron the system under consideration also occurs in mitochondria and microsomes especially within the main nephron, that is, in the proximal convoluted tubules and in straight tubules. It has been estimated that the metabolic potential of the system does not exceed 15-20% of its hepatic potential. In the lungs which are an important pathway of xenobiotic penetration, cytochrome P-450 is found in Clara cells of the bronchioli, macrophages, II type alveolocytes and in the cells of endothelial blood vessels. In the alimentary tract the maximal concentration of the system in the proximal segment of the small intestine and its gradual reduction towards the rectum have been noted. In the villi and intestinal folds, enterocytes located on the peaks of the mentioned structures are characterized by the highest contents and activity of biotransformatic enzymes. The localization and role of the system in the placenta, elastic vessels, brain and prostatic gland have also been discussed. PMID- 2097291 TI - Investigation of subclinical signs of autonomic neuropathy in the early stage of childhood diabetes. AB - It has been suggested that subclinical signs of neuropathy appear earlier than microvascular complications of diabetes. To evaluate the occurrence of autonomic nervous system dysfunction in the early stage of childhood diabetes, subclinical signs of autonomic neuropathy (resting heart rate, hyperventilatory arrhythmia, standing/lying heart rate ratio, orthostatic decrease in blood pressure, and increase in blood pressure during sustained handgrip) were investigated in 54 children with type 1 diabetes divided into three groups: 14 recent-onset diabetics (3 weeks after the diagnosis), 20 diabetics in the remission phase, and 20 patients after the remission phase. 30 healthy age-matched children were used as control group. The mean resting heart rates of the diabetic groups in the remission phase and after the remission phase were significantly higher than those in the healthy control group (81.7 +/- 5/min and 88.5 +/- 6/min vs. 72.2 +/ 8/min; p less than 0.01). The hyperventilatory arrhythmia in the group of diabetic children after the remission phase in comparison with the control group was significantly decreased (29.1 +/- 4/min vs. 22.7 +/- 3/min; p less than 0.01). In a few cases of the recent-onset diabetic group, the increase in resting heart rate, the decrease in hyperventilatory arrhythmia, and the standing/lying heart rate ratio proved to be significant. In the remission phase, the same parameters showed abnormal values in one third to one fifth of the children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097292 TI - Determination and characterization of arginine-vasopressin in extracted and unextracted urine and its urinary excretion in normal children and adolescents. AB - Arginine-vasopressin (AVP) was measured by radioimmunoassay in extracted and unextracted urine using two different antisera. The specificity of the assay was confirmed by high-performance liquid chromatography. By the use of a high specific antiserum, AVP can reliably be measured in unextracted urine. Measurements with a less specific antiserum revealed higher concentrations, probably due to nonspecific binding. The extraction of AVP by the use of octadecasilyl-silica columns is unable to separate the intact hormone from substances interfering with the assay. The urinary AVP excretion in 34 normal children and adolescents ranged between 3.5 and 120 ng/m2/24 h with a mean of 39.1 +/- 29.9 ng/m2/24 h. PMID- 2097293 TI - Inverse relationship between glucose metabolism and glucose-induced insulin secretion in rat insulinoma cells. AB - Slowly growing X-ray-induced rat insulinomas and derived cell lines have been used as a model system for glucose-induced insulin release. During perfusions of tumors transplanted under the kidney capsule, the carbohydrates glucose and D glyceraldehyde increased insulin secretion. These stimuli and the amino acids leucine and alanine also provoked insulin release in freshly isolated tumor cells. Under these conditions, glucose utilization had a Km of 4.6 mM and maximal velocity of 0.9 nmol/min/10(6) cells. A continuous cell line was established from such a preparation. In culture, glucose-induced insulin secretion was no longer detectable while responses to D-glyceraldehyde and amino acids were retained. Glucose metabolism in the cell line showed a decrease in Km to 0.7 mM glucose and an increased maximal velocity of 1.4 nmol/min/10(6) cells. Attempts to revert these alterations were undertaken using glucose-deficient culture medium to diminish glycolytic flux. Basal insulin release was lowered, while the growth pattern of the cells remained unchanged. Another approach involved the use of sodium butyrate which has been demonstrated to promote differentiation in other cell systems. Whereas sodium butyrate markedly increased cellular insulin content, the secretory responses were not improved. These results provide evidence that the loss of glucose-induced insulin secretion is paralleled by alterations in glucose metabolism. PMID- 2097294 TI - From PhD to parasites over 25 years: results, discussion and acknowledgements. PMID- 2097296 TI - The effect of glutamine on murine splenic leukocyte responses to T and B cell mitogens. AB - Murine splenic leukocytes cannot be stimulated to synthesize [3H]-DNA by various concentrations of either the T cell mitogens, Concanavalin-A (Con-A) or phytohaemagglutinin (PHA) or the B cell mitogen, lipopolysaccharide (LPS), unless glutamine is present in the culture medium. The optimum concentration of the T cell mitogens (Con-A, PHA) remained constant for all levels of glutamine while that of the B cell mitogen (LPS) increased as the concentration of glutamine in the medium increased. PMID- 2097295 TI - Effect of exogenous prostaglandin E2 and actinomycin D on plasma leakage induced by neutrophil-activating peptide-1/interleukin-8. AB - Neutrophil accumulation and plasma leakage were measured in rabbit skin at sites stimulated with recombinant human neutrophil activating peptide-1/interleukin-8 (NAP-1/IL-8). Neutrophil accumulation occurred at doses equal to or greater than 10(-11) moles NAP-1/IL-8 per site. Co-injection of prostaglandin E2 (PGE2) extended the threshold of inflammatory activity of NAP-1/IL-8 to less than 10( 13) moles/site and caused approximately three-fold increases in neutrophil accumulation and ten-fold increases in plasma leakage at the higher doses of NAP 1/IL-8 examined. Plasma leakage declined more rapidly than did neutrophil accumulation as lesions aged. It was postulated that an endothelial response may be initiated to limit plasma leakage during ongoing neutrophil emigration at sites stimulated with NAP-1/IL-8. The induction of vasodilatation by injection of PGE2 masked the decline of plasma leakage with time in lesions up to 120 min old. Co-injection of the RNA synthesis inhibitor, actinomycin D, failed to abrogate the decline of plasma leakage with time, suggesting that de novo protein synthetic events such as production of the vasoconstrictor peptide, endothelin, are unlikely to contribute to the mechanism that restricts plasma leakage in older lesions. Although plasma leakage induced by NAP-1/IL-8 is dependent on the emigration of neutrophils, the results indicate that a mechanism, independent of de novo protein synthesis, restricts the rate of plasma leakage per neutrophil as lesions age. PMID- 2097297 TI - Amelogenin gene similarity in vertebrates: DNA sequences encoding amelogenin seem to be conserved during evolution. AB - Mouse amelogenin cDNA was used in hybridization assays with genomic DNA, cut with the restriction enzyme Eco RI, from the edentulous chicken (Gallus domesticus), the monophyodont mouse (as control), diphyodont man, and the polyphyodont fishes Atlantic salmon (Salmo salar) and seawolf (Anarrhichas lupus). The hybridization assay was performed under stringent conditions with non-radioactive probes. Hybridization was obtained with mouse (6.4-kb band), man (9-kb and 13-kb bands), and seawolf (18-kb band) genomic DNA. This demonstrates DNA sequence similarities between these species, and supports the theory that DNA sequences encoding enamel proteins appear to be highly conserved during the evolution of vertebrates. Lack of hybridization in salmon and chicken may be due to sequence divergences or structural differences in an amelogenin gene analog, or it may be that no amelogenin gene is present in these animals. PMID- 2097298 TI - Cardiac output and stroke volume in swimming harbor seals. AB - Cardiac output was measured by the thermodilution method in three young harbor seals, at rest and while swimming up to the maximum effort for which they could be trained. Stroke volume was determined by counting heart rate simultaneously with determination of cardiac output. Cardiac outputs varied widely between surface breathing (7.8 ml.kg-1.s-1) and breath-holding while swimming under water (1.8 ml.kg-1.s-1). Stroke volume while at the surface was almost twice the volume while submerged. Surface cardiac output was always near maximal despite work effort, whereas submerged cardiac output gradually increased at higher work efforts. The cardiovascular performance of seals at the maximum MO2 we could induce from them is equivalent to that of the domestic goat. PMID- 2097299 TI - Primary structure of a pheromone-binding protein from Antheraea pernyi: homologies with other ligand-carrying proteins. AB - An antennal cDNA clone encoding the complete sequence (163 amino acids) of a pheromone-binding protein precursor from the male silk moth, Antheraea pernyi, was isolated using oligonucleotide probes. The cloned cDNA was expressed and the translation product detected by specific antibodies. The deduced protein sequence consists of a signal peptide of 21 amino acids and a mature binding protein of 142 amino acid residues. The predicted structure of this protein is homologous to binding-proteins from different insect species which have previously been identified, but shows no similarities to odorant-binding proteins from vertebrates, suggesting that soluble odorant-binding proteins in insects and vertebrates represent an evolutionary convergence. PMID- 2097300 TI - Circulatory water concentration in suckling and fasting northern elephant seal pups. AB - This study examined circulatory water concentrations in the neonatal northern elephant seal (Mirounga angustirostris) in order to determine how suckling and fasting would alter the percentage of water in the whole blood, plasma, and red blood cells (RBC). Plasma water concentration dropped by about 3% during suckling and recovered about 1% during the fast (92.38 +/- 0.48% less than 1 week old, 90.15 +/- 0.36% weaning, 91.02 +/- 0.68% end of fast). RBC water values during this time were more variable than plasma values: RBC water increased about 1% during the first 2 weeks of suckling (from 67.80 +/- 0.28% to 68.68 +/- 0.51%) but dropped to slightly below original neonatal values by weaning (67.15 +/- 0.63%). The first several weeks of fasting were marked by wide variability in RBC water, but by the end of the fast RBC water was comparable to that at weaning. These results indicate: 1) Northern elephant seal pups do not exhibit circulatory dehydration during 10 weeks of fasting; 2) Measurements of plasma or RBC metabolites (such as plasma glucose or RBC hemoglobin) may show variations or trends due not to metabolic regulation but rather to changes in circulatory water concentration. PMID- 2097301 TI - Absorption of ascorbic acid and ascorbic sulfate and ascorbate metabolism in common carp (Cyprinus carpio L.). AB - Ascorbate metabolism was analyzed in fasted common carp and carp offered diets lacking ascorbic acid or supplemented with ascorbic acid (AA) or ascorbic sulfate (AS). Ascorbic acid and ascorbic sulfate were analyzed in the contents collected from various parts of the digestive tract. The major site of the dietary ascorbate absorption was located in the first 20% of the anterior intestine region (58.7 +/- 10.2%), whereas absorption increased to 94.3 +/- 1.9% (in the whole gut). Considerable secretion of ascorbate into the initial part of the intestine was found (71 micrograms AA.g-1 dry food) in fish offered the diet lacking ascorbate, but this amount was completely reabsorbed in the following portions of the intestine. AS was concentrated in the contents of the digestive tract and the external marker method revealed no absorption of AS from the intestine. In fish fed the AA-supplemented diet, the concentration of ascorbate in plasma, hepatopancreas, kidney, intestine, spleen, and brain was significantly (P less than 0.01) higher than in similar tissues from the other groups, suggesting that ascorbic sulfate hydrolysis was ineffective. Small amounts of AS were found in the intestine and spleen of fish fed a diet supplemented with AS. Ascorbate analysis in the whole fish allowed the estimate of the catabolic rate of fasting and scorbutic-diet-fed fish, which amounted to 0.7% and 1.46% daily of the ascorbate body pool, respectively. There was no indication that ascorbic sulfate sulfohydrolase activity was induced in hepatic, kidney, or intestinal tissue of fish offered a diet with AS in comparison to other groups. It seems unlikely that cyprinid fish are able to utilize ascorbic sulfate as a vitamin C source, and thus resemble scurvy-prone mammals in this respect. PMID- 2097302 TI - Capillarity and diffusion distances in skeletal muscles in birds. AB - Tissue capillarity and diffusion distances were determined for red and white skeletal muscles of adult birds ranging in mass from 10.8 to 6200 g. In addition, literature values for capillarity and diffusion distances in skeletal muscles of mammals were incorporated into the data set. Muscle mass was closely coupled to body mass. However, no significant allometric relations were found for any of the other variables measured. Number of capillaries per fiber was not correlated with cross sectional area of individual muscle fibers. Thus, capillary density decreased in a hyperbolic manner against fiber area and diffusion distance decreased in a hyperbolic manner against the number of capillaries per muscle fiber. Red muscles had significantly higher numbers of capillaries per fiber and significantly shorter diffusion distances than did white muscles. The patterns for tissue capillarity and diffusion distances in avian muscle reported here are similar to values reported previously for mammalian muscles. In both taxonomic groups capillarity and diffusion distances are independent of body mass. In addition, diffusion distances are characteristic of capillaries distributed in random arrays through the muscle cross section. PMID- 2097303 TI - Reproducibility of mean transit time for maximal myocardial flow assessment by videodensitometry. AB - In the assessment of myocardial perfusion by ECG-triggered digital radiography, time parameters are calculated from the time density curve (TDC) and related to blood flow. Recently we developed a method which uses mean transit time (Tmn) as time parameter, and which is in accordance with the original principles of indicator dilution theory. In this approach, variability in vascular volume is excluded and Tmn-1, determined at maximal hyperemia, showed an excellent correlation with maximal flow in animal validation studies. For calculation of Tmn, however, a large part of the descending limb of the TDC has to be known for reliable extrapolation, and especially this part of the curve is subject to variability in image quality in man. Therefore we tested reproducibility of Tmn in 30 arteries in 20 patients. Tmn was derived from the TDCs, obtained from paired studies under identical circumstances with an interval of 10 minutes. Satisfactory images could be obtained in all but one patient. Image processing was performed in an identical way in the paired studies. Reproducibility proved to be excellent for all three coronary arteries. The absolute value of the relative differences between the first and second determination was 7 +/- 7% for the LAD, 6 +/- 3% for LCx and 4 +/- 2% for the RCA (mean +/- SD). Correlation coefficients between both measurements were 0.97, 0.95 and 0.95 for the respective arteries. Therefore, it is concluded that, using this approach, Tmn at maximal hyperemia can be determined reproducibly in man and used for maximal myocardial flow assessment. PMID- 2097304 TI - Quantification of regurgitant lesions by MRI. AB - We examined 46 patients with angiographically documented regurgitant lesions (26 patients with mitral regurgitation, 20 patients with aortic regurgitation) using an 0.5 Tesla magnet. In each patient a multislice-multiphase spinecho sequence in sagittal-coronal double angulated plane was performed to assess left and right ventricular volumes, ejection fraction and regurgitant fraction. Additionally a blood flow sensitive gradient echo technique was done to visualize direction and extension of the regurgitant jet. MRI data were compared with quantitative and qualitative assessment of regurgitation by angiography and echocardiography. Using the gradient echo technique MRI could demonstrate the regurgitant jet in all patients. A linear correlation for volume parameters by MRI and angio was found with best correlation for the left ventricular stroke volume (r = 0.82, p less than 0.0001). Furthermore MRI regurgitant fraction correlated with angiographically determined regurgitant fraction in patients with aortic regurgitation (r = 0.91, p less than 0.0001) and mitral regurgitation (r = 0.67, p less than 0.001), respectively. Semiquantitative assessment of regurgitation by gradient echo technique showed an agreement with angiographic grading by Sellers in 70% of mitral and 75% of aortic regurgitation, respectively. The comparison of MRI and color Doppler sonography showed only moderate correlation of r = 0.72 (p less than 0.01). PMID- 2097306 TI - Relationships between the lung-heart ratio assessed from post-exercise thallium 201 myocardial tomograms, myocardial ischemia and the extent of coronary artery disease. AB - Uptake of thallium (Tl)-201 in the lungs has been proposed as a measure of left ventricular dysfunction. In this study we were interested in pursuing two goals: 1) to assess possible relationships between the post-exercise Tl-201 lung-heart (LH)-ratio determined from the anterior view during SPECT-acquisition, myocardial ischemia and the extent of coronary artery disease; and 2) to explore the effects of coronary revascularisation procedures on the LH-ratio. The study group consisted of 145 patients with early and late postexercise Tl-201 tomograms, including 32 PTCA-patients with pre- and post-PTCA studies and 20 patients who underwent coronary artery bypass surgery (CABG) with corresponding pre- and post CABG studies. Ischemia was defined as evoked angina during the exercise test in combination with greater than or equal to 1 mm horizontal or downsloping ST depression on the ECG. The severity of coronary obstructions was assessed from coronary angiograms with a PC-based digital caliper technique; a stenosis was defined to be significant when its severity exceeded 50% diameter stenosis. The LH-ratio was defined by the ratio of the mean pulmonary counts and the mean myocardial counts assessed from corresponding regions of interest (ROI's) positioned over the left lung and the heart, respectively in the anterior view of a tomographic data acquisition procedure. Our results made clear that the LH ratio was not significantly different between patients with and without ischemia during exercise, and between patients with single vs. multiple vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097307 TI - Angiographic morphology of recurrent stenoses after percutaneous transluminal coronary angioplasty: are lesions longer at restenosis? AB - Angiographic morphology was analysed in 32 patients who developed restenosis after initially successful coronary angioplasty. The mean minimal luminal diameter of the dilated coronary segments increased from 0.9 mm to 2.3 mm after dilatation, but decreased to 0.9 mm at restenosis. The reference diameter was unchanged after dilatation and at restenosis. Mean stenosis length before the initial angioplasty was 7.0 mm but at the repeat procedure had increased to 8.7 mm (mean increase 1.7 mm, 95% confidence interval 0.6 to 2.8 mm, p less than 0.01). There were no significant differences in mean trans-stenotic pressure gradient and mean eccentricity ratio between the initial and repeat angioplasty procedures. In individual patients the changes in stenosis morphology were unpredictable, but overall stenoses tended to be longer at restenosis. In some patients stenosis length increased by several millimetres but the success rate of repeat angioplasty was high and the clinical importance of the changes in stenosis morphology are uncertain. PMID- 2097305 TI - International nifedipine trial on anti-atherosclerotic therapy (INTACT)- methodologic implications and results of a coronary angiographic follow-up study using computer-assisted film analysis. AB - Animal experiments demonstrated a significant suppressive effect of various calcium channel blockers on the formation of atherosclerotic lesions. Therefore, a prospective, placebo-controlled, randomized, double blind multicenter study was performed to investigate the inhibitory influence of the calcium channel blocker nifedipine (80 mg/day) on the progression of coronary artery disease in man. Study endpoints were changes of coronary morphology documented by coronary angiography with particular respect to the formation of new coronary stenoses. In 348 out of 425 patients included in the study, coronary angiograms were repeated after three years. The angiograms were standardized by induction of a maximal coronary vasodilation with high doses of nitrates and by using absolutely identical angiographic projections. Quantitative analysis of coronary cineangiograms was performed with the computer-assisted contour detection system CAAS. Parameters were mean and minimal diameter of all segments and minimal stenosis diameter, percent diameter stenosis, length and plaque area of all stenoses. Continuous intake of study medication was registered in 282 patients, 134 on nifedipine and 148 patients on placebo. In these patients, a total of 3808 coronary segments with 893 stenoses (greater than or equal to 20% diameter reduction in at least one angiographic projection) were compared on the baseline and follow-up cineangiograms. The changes in all angiographic parameters analyzed averaged over all patients by considering all angiographic projections analyzed, indicated significant progression of the disease (p less than 0.006). The average changes in all parameters were even about three times more profound, when in the individual patients only the respective projections indicating the maximal changes were considered for the calculation (p less than 0.001). However, with neither of these two analysis modes, the differences in progression between the treatment groups were statistically significant. In the follow-up angiograms, a total of 196 new coronary lesions (185 stenoses, 11 occlusions) were found at previously normal arterial sites. In patients on nifedipine, an average of only 0.58 new lesions per patient were detected versus 0.80 lesions per patient on placebo (-27%; p = 0.031). INTACT is the first prospective angiographic trial on the progression of coronary artery disease using computer-assisted quantitative coronary angiography in such a high number of patients. All parameters analyzed indicated significant progression of coronary artery sclerosis. Nifedipine had no influence on the progression of preexisting coronary stenoses, but inhibited significantly the formation of new angiographically recognizable lesions. Further prospective coronary angiographic trials with calcium channel blockers using a comparably exact method are needed to confirm the results of this study. PMID- 2097308 TI - Ischemic heart disease and regional left ventricular wall motion: a study comparing radial, centerline and a video intensity based slope technique. AB - Left ventricular regional wall motion in ischemic heart disease was evaluated and compared using three different methods based on radiographic ventriculograms. Radial method uses an internal reference system, and centerline method employs an external reference system, both methods are based on two frame analysis. The last method, an automated video intensity technique, analyzes on a frame by frame basis utilizing an external reference system. A total of 42 patients were included in the study, of these 12 had a history of myocardial infarction. Significant coronary artery stenosis was defined as 50% measured diameter reduction. Right coronary artery (29/42) was most commonly involved. Single vessel disease was present in 18 patients, two vessel disease in 15 and three vessel disease in eight patients. The radial method detected abnormal wall motion in 16/42 patients, centerline method yielded a detection accuracy of 22/42 and with the new technique, asynchrony was noted in 39/42 patients. All three methods detected regional wall motion abnormalities with a higher sensitivity in patients with prior myocardial infarction. The centerline method had highest sensitivity for the right coronary artery bed (55%). The radial method (45%) and the video intensity based technique (95%) had the highest sensitivity for regions supplied by the left anterior descending artery. PMID- 2097309 TI - Doppler documentation of aortic and tricuspid incompetence in left atrial myxoma. AB - A case of prolapsing left atrial myxoma with Doppler documented aortic and tricuspid incompetence is reported. The valves were structurally normal. Constant trauma to the central fibrous body by the prolapsing myxoma could be responsible for incompetence of tricuspid and aortic valves. PMID- 2097310 TI - The study of ocular hypotensive effect of 6-hydroxyethoxy-2-benzothiazole sulfonamide: a topical carbonic anhydrase inhibitor. AB - A newly synthesized topical carbonic anhydrase inhibitor, 6-hydroxyethoxy-2 benzothiazole sulfonamide (6-HS), was administered systemically and topically to alpha-chymotrypsin-induced glaucoma rabbits to evaluate its ocular hypotensive effect. A significant IOP lowering effect was observed after topical application of 50 microL of 3% 6-HS gel, but a dose of 50 microL of 3% 6-HS suspension failed to reduce IOP. The maximal magnitude of reduced IOP after topical gel instillation was 24.4%, very close to the result obtained following intravenous injection of 6 mg/kg of 6-HS (23.3%). However, the blood levels of 6-HS after topical instillation with 3% 6-HS gel was much lower than that following 6 mg/kg of 6-HS injected intravenously (less than 5%). Since a lower dose of 6-HS (1 mg/Kg) administered intravenously did not cause a significant drop in IOP, it is reasonable to deduct that the ocular hypotensive effect of 6-HS applied topically can then be attributed to the inhibition of intraocular carbonic anhydrase activity. It was also noted that a larger dose of intravenous administration of 6 HS (20 mg/Kg) had a more profound IOP and blood pressure reducing effect with moderate metabolic acidosis. PMID- 2097311 TI - Provocation and medical treatment in post-iridectomy glaucoma. AB - Residual glaucoma after an iridectomy in primary angle-closure glaucoma, or so called post-iridectomy glaucoma, is rather well recognized recently. It is also realized that probably different mechanisms in addition to the pupillary block mechanism co-exist in the same glaucoma eye. The efficacy of medical treatment for such glaucoma was evaluated by dark prone provocative test after timolol or pilocarpine topical instillation to compare with non-medication as control in 72 iridectomized eyes. The results revealed pilocarpine medication has only six eyes positive (8.3%) and significantly prevents IOP elevation in the test while timolol has no significant effect (23 eyes positive, 31.9%) when both were compared with the control study (31 eyes positive, 43.1%). The results may also suggest additional different mechanisms involved in this glaucoma. PMID- 2097312 TI - Influence of intraocular pressure on axial elongation. AB - The role of intraocular pressure (IOP) on axial elongation was studied by the following three experiments. 1) Thickness of the sclera in the lid-sutured-myopia of three monkeys was examined by light microscopy. The sclera of the experimental eye in the posterior pole was thinner than that of the control eye, but no differences were found in the equatorial and limbal parts of the sclera. 2) By increasing IOP, the scleral wall extensibility in 8 normal, enucleated rabbit eyes was measured by placing the foil strain gauges on the sclera. Extensibility of the sclera in the posterior pole showed a different response from that at the equator and in the limbus. 3) IOPs of the 184 human myopic eyes were measured by a Mackay-Marg tonometer in various postures. IOP elevations in high myopia and postural variations of IOP were obtained. From these experiments, it was suggested that IOP seemed to be one of the main factors in increasing the axis to the posterior pole. PMID- 2097313 TI - Effect of the calcium antagonist, nifedipine, on ischemic retinal dysfunction. AB - The therapeutic effectiveness of calcium channel antagonists (CCA) in hypertension and angina are well established. More recently, CCAs have also been demonstrated to ameliorate neurologic dysfunction that often accompanies ischemia associated with subarachnoid hemorrhage and stroke. We have hypothesized that retinal degeneration associated with ischemia may also result from the accumulation of calcium intracellularly, so-called "Ca++ overload". To test this hypothesis, a rat model of acute retinal ischemia, produced by direct occlusion of posterior ciliary and central retinal arteries, was developed. The extent of retinal dysfunction induced by ischemia was evaluated by electroretinograms (ERGs). Occlusion of the retinal arteries resulted in the disappearance of both a and b-waves during the occlusion period (30 minutes) in vehicle-treated rats. Total retinal ischemia did not produce any significant change in magnitude of ERG a-wave amplitude during three-hours of reperfusion. However, ERG b-waves amplitudes were significantly reduced by more than 60%. In rats, pretreatment with nifedipine (0.33 to 3.3 mg/kg, i.p.) 30 minutes prior to the occlusion of the retinal vessels produced a significant dose-dependent increase in the recovery of b-wave amplitude when compared to vehicle-treated rats. These data support the idea that "Ca++ overload", resulting from the deregulation of intracellular Ca++ homeostasis, is a primary factor involved in ischemic retinal degeneration and that CCAs can protect the retina from ischemic damage. PMID- 2097314 TI - Modulation of experimental autoimmune uveitis with formosanin-C in guinea pigs. AB - Formosanin-C, a diosgenin saponin, was isolated from a perennial herb, Paris formosana Hayata (Liliaceae) which has been used as a folk remedy for snake bite and as an anti-inflammatory or anti-neoplastic agent. Its effect on the development of S-antigen-induced experimental autoimmune uveitis (EAU) in guinea pigs was studied. Guinea pigs treated with formosanin-C (1.5 mg/kg/2 days and 0.5 mg/kg/2 days) were compared with untreated guinea pigs in regard to the development of EAU, lymphocytic proliferative responses, and anti-S-antigen serum antibodies. The higher dosage of formosanin-C (1.5 mg/kg) obviously delayed the onset of EAU. Treatment of this drug, 1.5 mg/kg and 0.5 mg/kg doses, significantly inhibited the specific lymphocytic response of lymph node and spleen cells to S-antigen. On the contrary, treatment in 1.5 mg/kg dose significantly increased the response of lymph node and spleen cells to the polyclonal T cell mitogen, phytohemagglutinin (PHA). Treatment with formosanin-C in both the 1.5 mg/kg and 0.5 mg/kg doses had a minimal effect on the lymphocytic response of lymph node to concanavalin-A (ConA), while a noticeable suppressive effect on the response of spleen cells to ConA was observed in the 1.5 mg/kg dose. This agent in 1.5 mg/kg and 0.5 mg/kg doses significantly inhibited the anti-S-antigen antibody production by days 14 and 18 postimmunization. This study suggests that formosanin-C, an immunomodulator, may offer a new approach to modulate the development of EAU. PMID- 2097316 TI - 13-cis retinoyl-beta-glucuronide in lacrimal gland fluid of rabbits treated with 13-cis retinoic acid. AB - When rabbits and humans are treated with orally administered 13-cis retinoic acid, the retinoic acid and a more polar retinoid metabolite appear in tears and lacrimal gland fluid. This study tested the hypothesis that this metabolite was a retinoyl-beta-glucuronide. Lacrimal gland fluid from rabbits treated with a pharmacologic dose of 13-cis retinoic acid was analyzed. Based on chromatographic retention time, absorbance maximum, and degradation to 13-cis retinoic acid by the enzyme beta-glucuronidase, it was shown that this retinoid metabolite is 13 cis retinoyl-beta-glucuronide. The 13-cis retinoyl-beta-glucuronide was also extracted from the lacrimal gland itself. It is concluded that 13-cis retinoyl beta-glucuronide is a major metabolite of 13-cis retinoic acid in the rabbit and that this retinoid is secreted by the lacrimal gland. PMID- 2097315 TI - Corneal and scleral penetration studies of 6-hydroxyethoxy-2-benzothiazole sulfonamide: a topical carbonic anhydrase inhibitor. AB - A newly synthesized topical carbonic anhydrase inhibitor, 6-hydroxyethoxy-2 benzothiazole sulfonamide (6-HS), was used as a model drug to determine its corneal and scleral permeabilities in rabbit eyes. The corneal permeability coefficient of 6-HS for short duration glaucoma and normal rabbit eye was not significantly different (its mean value was around 2.9 x 10(-6) cm/sec), while the corneal permeability coefficient for long duration glaucoma rabbit eye was 1.8 times greater than that for the normal eye. The sclera was found to have a higher permeability than the cornea in that after four hours perfusion the amount of drug which passed through the sclera was 11 times greater than that of the cornea. In addition, it was also noted that after topical instillation of 50 microL of 3% 6-HS gel the aqueous humor concentrations of 6-HS in short duration glaucoma eye and normal eye were not statistically different. PMID- 2097317 TI - Review: mediation of the ocular response to injury. AB - The structure of the anterior segment of the eye provide aqueous humour for metabolic traffic, regulation of intraocular pressure and the maintenance of a functional permeability barrier to separate internal compartments from general systemic influences. Irritative and injurous insults to the eye elicit an acute defensive miotic and vascular response which upsets the aqueous dynamics and provokes the influx of blood plasma proteins into the aqueous chambers. These events are initiated by antidromic activation of sensory elements within the anterior segment, releasing substance P and calcitonin gene-related peptide (CGRP) which, in lower mammals at least, stimulate respectively the miotic and vascular reactions. Considerable species differences can be found in the responsiveness of the eye to injury and in the effects of exogenous CGRP and substance P. PMID- 2097318 TI - The effects of the preincubation with vitamin B2-acid on ferredoxin-NADP+ reductase. AB - The effects of vitamin B2-acid on both cytochrome c reductase and diaphorase activities of ferredoxin-NADP+ reductase [EC 1.18.1.2] were investigated with enzyme kinetics. Vitamin B2-acid was shown to serve as an electron carrier for the two activities, as well as riboflavin or flavin mononucleotide (FMN). The two activities, however, were irreversibly affected by the preincubation of the enzyme with vitamin B2-acid under certain conditions, while riboflavin or FMN did not show such effects. PMID- 2097319 TI - Biosynthesis of biotin-vitamers by family Enterobacteriaceae. AB - The biosynthesis of biotin-vitamers from various carbon sources by the members of the Enterobacteriaceae as one of the groups of intestinal bacteria was investigated. The biotin-vitamers synthesized in each case included one or more of dethiobiotin (main product), 7-keto-8-aminopelargonic acid, and biotin. True biotin was shown to be synthesized under aerobic conditions but not under anaerobic conditions by each of several strains belonging to one of the genera, Erwinia, Escherichia, Proteus, and Serratia, and using culture media containing one of galactose, peptone, Polypepton, or casamino acid. In addition, a biotin precursor, pimelic acid, was also synthesized by several bacteria utilizing carbon sources such as maltose, mannose, galactose, peptone, or casamino acid. PMID- 2097320 TI - Effects of dietary excess amino acids on the concentrations of cholesterol, alpha tocopherol, ascorbic acid, and copper in serum and tissues of rats. AB - An experiment was conducted with growing rats to investigate the effects of feeding excessive specific L-amino acids for 8 days on serum and tissue cholesterol, alpha-tocopherol, ascorbic acid, and copper, and on liver microsomal cytochrome P-450. To a 10% casein diet were added 4% L-methionine, 5% L-cystine, 5% L-histidine, 5% L-threonine, 5% L-tryptophan, 5% L-phenylalanine, 5% L tyrosine, 6% L-valine, 7% L-isoleucine, 7% L-lysine, or 8% L-leucine. Excessive cystine and histidine increased serum cholesterol and alpha-tocopherol. Excessive cystine and methionine increased liver and kidney alpha-tocopherol and ascorbic acid. Excessive tyrosine and phenylalanine caused a marked increase in serum copper and ceruloplasmin activity, whereas excessive cystine, methionine, and histidine caused a decrease in the ceruloplasmin activity. Excessive histidine increased liver cytochrome P-450, whereas excessive tyrosine markedly decreased liver cytochrome P-450. PMID- 2097321 TI - Diurnal variations of cephalic exocrine pancreatic response in dogs. AB - The purpose of this study was to determine effects of oral stimulation of sucrose on the diurnal output of pancreatic secretion in conscious dogs. Male beagle dogs weighing 9-11 kg were prepared with gastric and duodenal fistulae. Once a day at 14:00 the animals were trained to eat a sufficient amount of a commercial stock diet to maintain their body weight. Gustatory receptors were stimulated at 9:00, 13:00, 15:00, and 18:00 for 5 min with 100 ml of 0.5% agar solutions containing 0.3 M sucrose. Pancreatic juice was collected every 5 min before and after stimulation, and volume flow and protein output were measured. As a result, we demonstrated daily fluctuations timed by feeding not only in the pancreatic basal secretions but also in pancreatic responses to the gustatory stimulation. These results suggest the significant role of taste stimuli in the nutrition of, at least digestion in, animals. PMID- 2097322 TI - Antioxidant activity of ubiquinol in solution and phosphatidylcholine liposome. AB - The antioxidant activities of ubiquinol and ubiquinone were measured in the free radical-mediated oxidations of methyl linoleate in solution and phosphatidylcholine liposomes in aqueous dispersion. Ubiquinol-10 suppressed the oxidation of methyl linoleate in hexane, although its reactivity toward peroxyl radical was about 10 times less than that of alpha-tocopherol. Ubiquinone-10, on the contrary, did not show any antioxidant activity. On the other hand, ubiquinol 10 inhibited the oxidation of phosphatidylcholine liposomal membranes as efficiently as alpha-tocopherol. When both ubiquinol-10 and alpha-tocopherol were present, ubiquinol-10 decreased first and alpha-tocopherol decreased after all ubiquinol-10 was consumed in both solution and liposomes. These results and electron spin resonance (ESR) study suggest that ubiquinol-10 regenerates alpha tocopherol by reducing alpha-tocopheroxyl radical. PMID- 2097324 TI - Highly sensitive determination of PLP in human plasma with HPLC method. AB - To investigate the validity of using HPLC procedure with the fluorescence detection for the estimation of the pyridoxal 5'-phosphate (PLP) concentration in human blood plasma, we modified the conditions of our previous HPLC method for PLP. By changing the pH of the mobile phase (pH 5.5) and by altering the detection wavelengths in fluorescence (excitation at 322 nm and emission at 417 nm), both the improved sensitivity for pyridoxic acid 5'-phosphate and elimination of interfering extraneous peaks were attained. We reported the total vitamin B6 content of healthy adult volunteers obtained by this HPLC method. PMID- 2097323 TI - Membrane stabilizing effect of vitamin E: existence of a hydrogen bond between alpha-tocopherol and phospholipids in bilayer liposomes. AB - In order to elucidate the existence of a hydrogen bond between alpha-tocopherol and phospholipids in bilayer liposomes, the effects of the presence or absence of alpha-tocopherol or its acetate on either the permeability of liposomes to chromate ions or the fluidity of liposomes composed of the different kinds of lecithin [egg yolk phosphatidylcholine (EPC), 1-oleoyl-2 palmitoylphosphatidylcholine (OPPC), or 1-O-oleyl-2-O palmitoylphosphatidylcholine (OPPCE)] were examined. From the results obtained, it was concluded that the hydroxyl group of alpha-tocopherol is hydrogen bonded to the carbonyl group of a fatty acid ester in the phospholipids of bilayer liposomes in order to retain alpha-tocopherol molecule in the space close to the surface of membranes formed by the unsaturated fatty acid moiety of phospholipids. PMID- 2097326 TI - The effect of dietary protein source on plasma cholesterol level and fecal steroid excretion in obese mice. AB - Both goldthioglucose (GTG)-treated and the genetically obese (C57BL/6J ob/ob) mice were fed semisynthetic diets containing either soy protein isolate (SPI) or casein as a protein source, or laboratory chow. In GTG-induced obese mice, the plasma cholesterol level correlated positively with their body weight. The level was highest in mice fed high-fat diet, and lowest in ones fed laboratory chow. No difference was observed between SPI and casein groups whether the diet was low fat or high-fat. Thus, in the GTG-treated mice, SPI did not have a hypocholesterolemic effect while dietary fat had a hypercholesterolemic effect, and laboratory chow contained some component(s) which can lower the plasma cholesterol level. Both neutral and acidic steroid contents in feces of the SPI group were not different from those of the casein group, and both groups of mice excreted a smaller amount of steroids than mice fed laboratory chow. Results of essentially the same tendency were obtained with normal mice regarding the effects of SPI and casein, although the degree of hypercholesterolemia was lower in high-fat-fed normal mice than in similarly fed GTG-treated mice. These results strengthened the inverse correlation between the amount of fecal steroids and the plasma cholesterol level upon feeding various proteins, indicating that the former is one of the important factors that determine the latter. The ob/ob mice showed a marked hypercholesterolemia irrespective of the kind of diet. The amount of fecal steroids was highest in the laboratory chow group and lowest in the casein group. This indicates that some factor(s) other than fecal steroid excretion is dominantly responsible for their hypercholesterolemia. PMID- 2097327 TI - Effects of a high protein diet on bone formation and calcium metabolism in rats. AB - The effects of a high protein diet on bone formation and calcium (Ca) metabolism were evaluated in rats using an ectopic endochondral bone induction model. A control diet (18% casein) or a high protein diet (18% casein + 20% lactalbumin) was given to 50-day-old rats. Ten days after the feeding of the experimental diet, rats were intramuscularly implanted with demineralized bone powder (day 0). On day 14 and day 21, the implanted bone powder was harvested, and blood and urine samples were also obtained. Urinary Ca excretion was not increased on day 12-14; however, it was elevated on day 19-21 in rats fed the high protein diet compared with rats fed the control diet. The high protein diet remarkably stimulated urinary sulfate excretion in both sampling periods, which reflected dietary sulfur-containing amino acids contents. Also, rats fed the high protein diet exhibited a decrease in serum Ca concentrations. There was little difference in Ca contents and the activities of alkaline phosphatase and acid phosphatase in the implants between control group and high protein diet group on day 14 and day 21. Histological examination in the implanted demineralized bone powder on day 14 indicated only cartilage in rats fed the high protein diet in contrast to the occurrences of osteogenesis and remodeling in those fed the control diet. Retarded bone formation in rats fed the high protein diet might be owing to, in part at least, a restricted amount of Ca utilized at the stage of cartilage calcification. PMID- 2097325 TI - Concentrations of lactoferrin and iron in human milk at different stages of lactation. AB - Lactoferrin (LF) was isolated from human milk by serial procedures of 45% ammonium sulfate precipitation, CM Sephadex C-50 ion-exchange chromatography, Sephadex G-100 gel filtration, and Cu-affinity chromatography, in which 59Fe lactoferrin was used as the tracer. The recovery of LF from human milk was 3.3%. LF from human milk was a single component having a molecular weight of 78k on SDS PAGE, and showed pI 8.02 by isoelectric focusing on slab gel. The LF concentration was measured by rocket immunoelectrophoretic assay using anti-human LF antiserum in human colostrum and milk, from 1 to 60 days after parturition (125 samples). The LF concentrations in colostrum (1-3 days of puerperium, n = 35), the transitional milk (4-7 days, n = 60), and mature milk (20-60 days, n = 30) were 6.7 +/- 0.7, 3.7 +/- 0.1, and 2.6 +/- 0.4 (mean +/- SEM) g/liter, respectively. Both the LF and total protein (TP) concentrations showed significantly inverse correlations with the days after parturition (p less than 0.001). The lactoferrin/total protein ratio (LF/TP) in the mature milk (16.1 +/- 1.4%) was significantly less than that in the colostrum (20.4 +/- 1.2%, p less than 0.05) and the transitional milk (21.4 +/- 0.9%, p less than 0.05). Furthermore, iron concentration (Fe) in human milk was also measured by the internal standard technique of the spiked method on atomic absorption, and the lactoferrin iron saturation (LS%) was calculated. Neither Fe nor LS% had significant difference among these three stages of the lactation. The means (n = 125) of Fe and LS% were 60.6 +/- 5.4 micrograms/100 ml and 11.8 +/- 1.1%, respectively. However, significant correlation was observed between LF and Fe (p less than 0.005) or between LF/TP and both of Fe (p less than 0.05) and TP (p less than 0.001) in the mature milk. These results suggest that the mechanism stimulating the synthesis and secretion of LF is different from those of other proteins and LF can play variable roles in iron nutrition of babies at the different stages of lactation. PMID- 2097328 TI - Influence of a high ambient temperature and administration of clenbuterol on body composition in rats. AB - This study was conducted to determine the effects of the oral administration of the beta agonist clenbuterol on body composition in growing rats reared under a high ambient temperature. Forty-three male Wistar-strain rats of 5 weeks of age were divided into 6 groups: 2 levels of ambient temperature (26 and 33 degrees C) and 3 dose levels of clenbuterol (0, 50, and 100 micrograms/kg diet) under each ambient temperature. All rats were raised for 7 weeks. From the 3rd week, rats in the clenbuterol-treated groups were fed a diet containing clenbuterol. Both the lipid and cholesterol content in the rat liver, and the epididymal adipose tissue weight were significantly higher in the hot environment than in the temperature environment. Body fat component was significantly higher in rats in the 33 degrees C groups in comparison with that in rats in the 26 degrees C groups. On the other hand, body protein component was significantly lower in the 33 degrees C groups than in the 26 degrees C groups. Although the administration of clenbuterol significantly decreased fat and increased protein in the 26 degrees C groups, no particular influence of clenbuterol administration on body composition was observed in the 33 degrees C groups. PMID- 2097329 TI - Effect of vitamin A deficiency on oxalate uptake by rat intestinal brush border membrane vesicles (BBMV) and its contribution towards urolithiasis. AB - The intestinal uptake of [14C]oxalate, [14C]glyoxylate, and [14C]glycolate are studied in brush border membrane vesicles (BBMV) isolated from vitamin A deficient and pair-fed control rats. The data obtained indicate that oxalate and its precursors are transported across the BBMV by passive diffusion. The intestinal uptake of glyoxylate and glycolate remains unaltered in vitamin A deficiency, while uptake rate of oxalate was significantly increased (p less than 0.01) in vitamin A-deficient rats as compared to pair-fed controls. In conclusion, the results indicate that vitamin A deficiency leads to hyperabsorption of oxalate through the gut. PMID- 2097330 TI - Formulation, nutritive value and sensory evaluation of a new weaning food based on sweet corn (Nutrimaiz) dehydrated pulp. AB - The objective of the present work was to develop a formulation for complementary infant and child feeding employing linear programing as a mathematical model for optimization. High lysine/high tryptophan sweet corn pulp in the dehydrated form was used as the main ingredient. The restrictions imposed on the model were nutrient requirements, adequate protein/energy ratio and minimum cost. The formula derived by the computer (FC) matched the amino acid requirements, the protein/energy ratio (NDPCal%) and was rated high in laboratory tests in terms of sensory qualities. The cost determined for this formula was competitive in relation to commercial products used for the same purpose. Formula A, which contained 5% more sweet corn pulp and 10% less whole powdered milk, did not differ in nutritional, sensorial and functional properties from the formula FC and was chosen for the field acceptability trial because of its lower cost. Formula A had protein efficiency ratio and Biological Value similar to casein for the rat but protein digestibility and net protein utilization were statistically lower (p less than 0.05) for formula A than for casein. Acceptability tested on children who were 8-18 months of age ranged from 80-90%, average value 87%. PMID- 2097331 TI - Maternal dietary leucine supplementation affects apparent lactational activity and pup development in rats. AB - Previous work from this laboratory has shown mildly elevated dietary leucine to alter the rhythm of prolactin secretion and to interfere with normal estrous cycling in the intact female rat. In this study, we have determined whether these observed effects on prolactin and cycling in turn affected fertility, gestation, mammary gland development or mammary gland morphology during lactation. Groups of control and leucine-supplemented mothers were mated with tested male breeders and a daily record was kept of pup births, pup deaths and general health and development of the pups. The day after weaning, mammary tissue was removed from dams in both groups and prepared for histological examination. In light of the previous results showing estrous cycle interruption and altered prolactin secretion, we report what was a surprising lack of effect of leucine supplementation of fertility, maintenance of gestation or overall development of the mammary glands in this species. Interestingly, however, dietary leucine supplementation was found to markedly after the histological appearance of lactating mammary tissue and to cause a significant increase in the number of litters that contained notably underdeveloped pups. PMID- 2097332 TI - Relationship among malondialdehyde, TBA-reactive substances, and tocopherols in the oxidation of rapeseed oil. AB - Relationship among malondialdehyde (MDA), 2-thiobarbituric acid (TBA)-reactive substances (TBA-RS), and tocopherols in the oxidation of rapeseed oil was investigated. MDA was determined by a new HPLC method with chemical derivatization. When the oil was heated at 170 degrees C, TBA-RS and MDA increased. The contents of TBA-RS were approximately 1.6 times higher than those of MDA. Correlation between the increase in formed MDA and the decrease in tocopherols was observed. When the oxidation of the oil was initiated using 2,2' azobis-(2,4-dimethylvaleronitrile) at 40 degrees C, TBA-RS dramatically increased during the initial stage and reached plateau. Thereafter, little increase was observed. The relative ratio of MDA to TBA-RS was much lower in the reaction performed at 40 degrees C than that observed at 170 degrees C. These results indicated that the decrease of tocopherols was accompanied by the increase of MDA but TBA-RS did not correlate with the change of tocopherols. PMID- 2097333 TI - Cerebral blood flow velocity recordings and the prediction of intracranial haemorrhage and ischaemia. AB - Doppler ultrasound was used to study prospectively cerebral and cardiovascular hemodynamics in a cohort of 120 preterm infants to see whether it was possible to predict infants at increased risk of developing cerebral pathology. The infants were divided into four outcome groups: Group I (n = 65, median gestation = 30 weeks) did not develop periventricular haemorrhage (PVH) nor periventricular leukomalacia (PVL) Group II (n = 43, median gestation = 28 weeks) developed PVH as the first or only cerebral lesion Group III (n = 7, median gestation = 29 weeks) developed PVL as the first or only cerebral lesion Group IV (n = 5, median gestation = 28 weeks) developed PVH and PVL simultaneously. Cerebral blood flow velocity (CBFV) and aorta blood flow velocity (ABFV) recordings made before the onset of PVH or PVL were compared between the four groups on each postnatal day but it was not possible to demonstrate a statistically significant difference between these variables in the four outcome groups. We conclude, therefore, that it is not possible to identify the infants who will go on to develop haemorrhage or ischaemic lesions on the basis of Doppler cerebral haemodynamic studies. PMID- 2097334 TI - Cervical ripening of the rat in dependence on endocrine milieu; effects of antigestagens. AB - The circumstances which cause the ripening of the cervix during the initial phase of parturition are still unexplored. In addition, complications during labour such as cervical dystocia still necessitate cesarian section. Therefore we examined the biomechanical alterations of the cervix during the last trimester of pregnancy. We developed a special method to measure dilatation and resistance of the rat cervix. After testing several substances, the antigestagen Mifepristone turned out to be most effective in causing cervical softening. Further investigations with light and scanning electron microscopy showed an increase of collagen and a possible loosening of collagen fibers after antigestagen treatment. Therefore it might be possible to use Mifepristone, perhaps in combination with a prostaglandin to promote cervical ripening when certain obstetric problems arise. PMID- 2097335 TI - A method of macro-auditing and assessing the preventability of infant mortality using large volume computerized files. AB - We present a method for auditing and evaluating infant mortality with the aid of a preventability grading system, based on national computerized files of livebirths and infant deaths. Diagnostic categories and specific causes of deaths were classified into one of the following three preventability grades: Preventable (P), Possibly Preventable (PP) and Non Preventable (NP). This classification was then applied to two different scales: Preventability of Condition (PC) and Preventability of Death (PD) from which a third scale- Preventability of Mortality (PM)--was derived. The method was then applied to matched records of 39,786 livebirth and 452 infant death certificates between 1977 and 1984, in a semi-urban region in Israel encompassing 220,000 inhabitants. Comparison of mortality rates, according to the proposed preventability scores, demonstrated that higher infant mortality rate in non-Jewish population, or in Jewish mothers with a lower educational, was present only in the preventable categories (P or PP), while death rates due to non preventable causes were identical for all groups. The suggested macro-auditing method facilitates the assessment of large scale infant mortality rates in terms of preventability. PMID- 2097336 TI - Interval between birth of the first and the second twin and its impact on second twin perinatal mortality. AB - We investigated the impact of a long interval between the birth of the first and the second twin on second twin perinatal mortality (PNM). National data in the Swedish Medical Birth Registry were used on 7533 second twins born in Sweden between 1973 and 1985. PNM as a function of the time interval between the births of the twins was studied in data from two time periods: during 1973-78 (n = 4008) and 1979-85 (n = 3525). During the first period, PNM was significantly higher at intervals of 30 min or more between the births of the twins than at shorter intervals (chi 2 = 11.1, p less than 0.001). When studied within broad birth weight classes, a significant trend was seen for twins weighing 1500-2499 g with an increasing interval (chi 2 = 8.1: p less than 0.01). A non-significant trend was also found for twins weighing less than 1500 g but none for twins weighing greater than or equal to 2500 g. During the second period, abdominal delivery of the second twin after vaginal delivery of the first twin was significantly more common than during the first period (2.0% vs 0.3%, chi 2 = 52.7, p less than 0.001). During the second period, the interdelivery interval had little impact on second twin PNM. The results of this study seem to indicate that with modern management of labor and delivery, as seen in Sweden since 1979, the interdelivery interval has little impact on second twin PNM. PMID- 2097337 TI - Adherence of group B streptococci to buccal epithelial cells in neonates with different gestational ages. AB - Adherence of group B streptococci to buccal epithelial cells was determined in 81 neonates with different gestational ages. There was a significant curvilinear increase in adherence in premature neonates with decreasing gestational ages. Amniotic fluid did not inhibit attachment of group B streptococci to epithelial cells. Increased adherence of group B streptococci to premature neonates may explain, in part, the increased susceptibility of these infants to disease from this organism. PMID- 2097338 TI - Growth dynamics of the heart from perinatal period to childhood. AB - In order to obtain information useful for the diagnosis of fetus and newborn heart disease, we established a theoretical model of perinatal cardiac growth. We measured with the use of ultrasonic cross-section imaging system the mitral valve ring dimension, tricuspid valve ring dimension, and total cardiac dimension as morphological parameters of the heart in 45 cases composed of fetuses and children. The obtained data were entered into a computer. With the use of these data, simulation was made on the basis of the general theory of biological development. The present simulation showed that from the fetal stage to childhood the growth rates of the foregoing three morphological parameters mutually differ, but during the period of growth to the age of 12 years of the present study, they all demonstrated continuous growth up to 3 1/2 years after birth when they reached a growth saturation level. PMID- 2097339 TI - A computer-based behavior monitoring system for low-birth weight infants under intensive care. AB - For the intensive care of low-birth weight infants, it is important to continuously monitor behavioral changes. From this point of view, we have developed a computer-based monitoring system to analyze the body movements of low birth weight infants under intensive care. The system consisted of a video recorder with a micro CCD camera for observing infant's body movements and a real time image processor for analyzing video frames. A 16 bit personal computer equipped with an image processor converted a video frame into a binary image that is a 256 by 256 matrix of pixels. The computer assessed each pixel of the matrix to determine whether the brightness changed between successive binary images or not. The number of changed pixels was counted every 1/30 sec, and such change reflected a infant's body movements. Using the system, body movements of a low birth weight infant in an incubator were videotaped during 24 hours and analyzed. Results indicate that the behavior monitoring system developed in the present study has not only the ability to detect occurrences of movements of low-birth weight infants, but also the ability to qualitatively describe the pattern of movements. PMID- 2097340 TI - Maternal serum lipid profile in pregnancies complicated by hypertensive disorders. AB - Plasma lipoprotein, cholesterol and triglycerides were determined in 34 hypertensive pregnant patients and in 17 healthy full term pregnant women. Pregnancy induced hypertension was diagnosed in 21 patients and chronic hypertension in the remaining 13 women. Serum triglyceride levels were significantly elevated in the hypertensive patients. This elevation was not influenced by either the severity or the etiology of the hypertension. The total cholesterol/HDL and the LDL/HDL ratios were significantly elevated in the severely hypertensive patients, and furthermore the LDL/HDL ratio was elevated in patients receiving anti-hypertensive treatment. The lipid profiles found in hypertensive pregnant patients could be associated with enhancement of pathological lipid deposition in predisposed vessels such as the uterine spiral arteries. Furthermore, the hypertriglyceridemia found in the hypertensive patients may be associated with the hypercoagulability reported in pregnancy induced hypertension. PMID- 2097342 TI - Recurrent respiratory symptoms in the first year of life following preterm delivery. AB - Recurrent respiratory symptoms in the first year of life following preterm delivery were documented in two studies. In the first study a questionnaire was sent to all parents of preterm very low birth weight (VLBW) infants who had been admitted during a six-month period to the Neonatal Intensive Care Unit (NICU) at King's College Hospital (KCH) and who lived within the local district. Questionnaires were also sent to parents of a control group of infants who were recruited by random selection. All the controls lived locally and were delivered at KCH in the same six-month period as the study group, but were born at 37-41 weeks of gestation and had had no neonatal problems. The questionnaire documented frequency of cough and wheeze, medication and hospital admissions. Recurrent respiratory symptoms (wheeze or wheeze and cough) occurred in 65% of the preterm VLBW infants but only 33% of the controls p less than 0.001. Less than 10% of infants in either group had received bronchodilator therapy. Admission to hospital in both groups was more common amongst children who had recurrent wheeze (p less than 0.01). In the second study all preterm VLBW infants admitted to the NICU in a six-month period were followed prospectively over the first year of life. The nature and frequency of respiratory symptoms and frequency and length of re-admission was documented and related to the duration of neonatal ventilation. Twenty-three of the 44 preterm VLBW infants (53%) followed prospectively had recurrent wheeze and/or cough.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097341 TI - Maternal kinetics of morphine during labour. AB - The disposition of parenterally administered morphine was investigated in 13 nulliparous parturients in comparison with six healthy non-pregnant women of child-bearing age. Morphine was administered intravenously or intramuscularly and repeated venous blood samples were taken up to 360 minutes after the dose, or until delivery. At delivery samples were taken from the umbilical artery and vein. The plasma concentrations of morphine and M3G (morphine-3-glucuronide) were determined. The elimination half-life of morphine was shorter (43 +/- 19 versus 84 +/- 40 min) and the plasma clearance larger (3.4 +/- 1.4 versus 2.0 +/- 0.5 l/min) in the parturients than in the non-pregnant women. There was no difference in the apparent volume of distribution of morphine between those two groups. The time to peak plasma concentration of M3G was shorter (11 +/- 3 versus 21 +/- 6 min) and the M3G/morphine concentration ratio at 10 minutes higher (6.4 +/- 1.0 versus 3.4 +/- 0.6) in parturients than in non-pregnant women. In all but one infant, three of whom were born within three hours after the dose, no morphine was detectable. The rapid elimination of morphine by the parturients, resulting in only a short period of intrauterine exposure of the fetus to this drug, may be of clinical importance in the choice of obstetric analgesic agent. PMID- 2097343 TI - Cholesterol side-chain cleavage activity in the human umbilical cord in vitro. AB - With a view to establish whether cells of the human umbilical cord possess cholesterol side-chain cleavage activity, homogenates of term umbilical cord obtained following spontaneous vaginal delivery from uncomplicated pregnancies (n = 6; 38-40 weeks gestation) were incubated with 26-14C cholesterol. Controls were homogenates heating in a boiling water bath for 10 min. Proof of the existence of cholesterol C-20, 22-desmolase activity in the viable tissue was established by associating radioactivity due to the labelled carbon 26 of 26-14C cholesterol with the p-bromophenacyl ester of isocaproic acid by reverse-isotope dilution analysis. The desmolase efficiency expressed as specific activity of 14C isocaproic acid, dpm g-1 tissue varied from 110 to 351 with a mean of 202. The small but definite conversion indicates that the cholesterol side-chain cleavage reaction previously believed to be exclusive to the steroidogenic pathway operating in the adrenal, gonads and placenta does exist in the human term umbilical cord in vitro. PMID- 2097344 TI - A cytoplasmic factor involved in the expression of resistance to C8-ATC in Saccharomyces cerevisiae. AB - A dozen mutants of Saccharomyces cerevisiae, resistant to C8-ATC have been characterized. C8-ATC was previously established as a biologically toxic compound. Frequency of mutants (10(-7)) was typical for spontaneous mutations. One very stable mutant was characterized extensively. The genetical analysis revealed that resistance in this mutant was determined by single-gene mutation. The rho 0 cells, obtained by ethidium bromide (EB) mutagenesis of the resistant strain, were completely devoid of resistance. A large percentage of rho- cells, obtained by a moderate EB treatment of resistant cells were still able to express resistance to C8-ATC. Therefore we hypothesized that, in our particular strain, a cytoplasmic factor is involved in nuclear determination of resistance. PMID- 2097345 TI - Purification and properties of a malolactic enzyme from Leuconostoc oenos ATCC 23278. AB - The malolactic enzyme of Leuconostoc oenos ATCC 23278 was purified 136fold. The molecular weight was estimated at 132,000 when determined by gel filtration. The enzyme contained two identical subunits (Mw = 66,000 using sodium dodecyl sulfate gel electrophoresis). The malolactic enzyme catalyzes the NAD(+)- and Mn(+) dependent reaction L-malate----L-lactate + CO2. The apparent Km values for malic acid, NAD+, and Mn2+ were 17 mM, 0.044 mM, and 0.017 mM, respectively. The optimal pH and the optimal temperature for activity were 5.0, and 37 degrees C, respectively and the isoelectric point was pH 4.30. L-lactate and ethanol were non-competitive inhibitors, whereas succinate, citrate, and D-tartrate showed competitive type inhibitions. PMID- 2097347 TI - Plasma fibrinogen levels in stroke. AB - Plasma fibrinogen levels were estimated in 56 patients of stroke, admitted in the hospital within 24 hours of symptoms. The levels were found to be raised significantly (531.73 +/- 74 mg%) compared to those of the age and sex matched control group (445.78 +/- 92.28 mg%). When the levels in stroke group with one risk factor were compared to those of individuals with comparable control group with same risk factor, a significant difference was observed in hypertensive, smokers, alcoholics and atherosclerotic stroke groups, which indicates that the observed rise is related to phenomenon of stroke rather than the associated risk factors. However, the rise observed in hypertensive stroke group (554.26 +/- 47.08 mg%) is significantly more (p. less than 0.01) than that occurring for nonhypertensive stroke group (497.82 +/- 93.12 mg%) indicating that the presence of hypertension does contribute to the rise. PMID- 2097346 TI - Ultrastructural features of microbial colony organization. AB - The ultrastructure of microbial colonies was studied. Inside the colonies three types of intercellular contacts were demonstrated. In the colonies of Gram negative bacteria, the cells were found to be connected by tight adhesions of outer membranes of the cell walls and membrane bridges. In the colonies of Gram positive bacteria, the intercellular contacts were formed by fusion of peptidoglucan layers of the cell walls. Bacterial cells were differentiated by the presence of a capsule-like envelope. The obtained data indicate the existence of elements of cellular cooperation and specialization in microbial colonies. PMID- 2097348 TI - Role of hyperbaric oxygen therapy in the rapid control of gas gangrene infection and its toxaemia. AB - Fifteen cases of proved gas gangrene infection were studied to assess the rapidity of control of infection and associated toxaemia, by hyperbaric oxygen therapy at 2 1/2 atmospheres pressure. Within 3-5 sittings, all the cases (100%) were found to become devoid of clostridial organisms as judged by smear and culture methods. PMID- 2097349 TI - Histiocytosis-X: role of histology and S-100 protein in grading the severity of disease. AB - Histiocytosis-X encompasses a wide clinical spectrum from a benign localised lesion to acute generalised disease with malignant behaviour. We have reviewed material from our 18 retrospective cases comparing histological features with clinical data. Degree of positivity for S-100 protein was studied by immunoperoxidase method. Our results indicate that diagnosis of histiocytosis-X necessitates histological confirmation but grading of histological criteria and S 100 positivity do not allow prediction of severity and extent of the disease. PMID- 2097350 TI - Pediatric ocular trauma--a clinical presentation. AB - A year long study of ocular injuries in children below the age of 15 years was conducted in the Ophthalmology Department of a general hospital. Fortyfour cases were studied. Of these 45.45% were in the age group of 6-10 years. The male to female ratio was 5.28 : 1. Pointed objects viz. sticks, wires etc. were found to be the common causative agents; the recent trend being of bow and arrow injuries. Ocular perforation was observed in 28 cases. On follow up of all the cases with ocular trauma, only 12 patients were found to have a visual acuity better than 6/18; perception of light was absent in 7 patients. A need for increased parental awareness and supervision of children is stressed upon. PMID- 2097351 TI - Paroxysmal nocturnal hemoglobinuria: a study of 17 cases. AB - Retrospective analysis of 17 cases of paroxysmal nocturnal hemoglobinuria (PNH) was carried out. The presenting feature of anaemia and hemoglobin of less than 9 gm% were observed in all cases. Fever, jaundice and bleeding tendency were observed in 8, 8 and 7 cases respectively. Bone marrow examination revealed megaloblastic features, erythroid hyperplasia and hypocellularity in 8, 7 and 2 cases respectively. Fourteen cases were refractory to the treatment, while only 3 showed response. PMID- 2097352 TI - Gastric carcinoma in the young (review of 14 cases). AB - A retrospective study of 14 cases of gastric carcinoma in the age group of 19 to 35 years is presented. The relevant literature has been reviewed. PMID- 2097353 TI - Boari flap calycovesicostomy: a salvage procedure for giant hydronephrosis due to ureteropelvic junction obstruction. AB - The surgical management of two patients with giant hydronephrosis in a solitary kidney treated by Boari flap calycovesicostomy is presented. In one patient, this operation was done following unsuccessful previous pyeloplasty, while in the other this was done as the primary operation. Though free reflux was observed in both the cases, the refluxed contrast emptied satisfactorily after double voiding. No deterioration of renal function was noted during the follow-up period of 12 months. PMID- 2097354 TI - Marfan's syndrome: a neonatal presentation (a case report) PMID- 2097355 TI - Solitary extramedullary plasmacytoma (a case report). AB - Solitary plasmacytoma of the upper air and food passages is a rare tumour. This paper deals with such a case along with a brief account of the etiology, clinical features and therapeutic measures. PMID- 2097356 TI - Cystic degeneration in an adenomyoma (a case report). AB - Cystic degeneration though often seen in a leiomyoma, has not been reported so far in an adenomyoma. Hence, a unique case of cystic degeneration in an adenomyoma of the uterus is presented. PMID- 2097357 TI - Congenital lipodystrophy with defective leucocyte function (a case report). AB - A 6 1/2 year old female child with congenital lipodystrophy is being presented. The noteworthy feature in this case was the defective leucocyte function and its association with tuberculous pericardial effusion. PMID- 2097358 TI - Effect of intravenous infusion of verapamil in patients of severe hypertension. AB - Thirty patients with diastolic blood pressure of 120 mm Hg or more were administered a bolus dose of verapamil (0.15 mg/kg) followed immediately by an intravenous infusion at a rate of 0.005 mg/kg/min for one hour. The patients were monitored during this period and three hours following the discontinuation of the infusion. The systolic, diastolic and mean blood pressures before verapamil administration were 221.4 +/- 7.5, 134.3 +/- 2.7 and 163.4 +/- 4.1 mm Hg respectively, which decreased to 170.1 +/- 5.2, 99.1 +/- 3.7 and 122.8 +/- 3.6 mm Hg after intravenous bolus of verapamil. The fall in all the levels of blood pressure was significant (p less than 0.001) and was maintained at the lower levels throughout the infusion period and even three hours after discontinuation of the therapy. No untowards effects were observed and there was no significant change in heart rate and electrocardiogram. It, thus, proves to be an useful addition to the therapeutic armamentarium in the acute management of severe hypertension. PMID- 2097359 TI - Duane's retraction syndrome with facial hemiatrophy (a case report). AB - This report deals with a young girl with Duane's retraction syndrome who also had left facial hemiatrophy (Parry-Romberg syndrome). Report of such an association is probably first of its type to be documented in literature. PMID- 2097360 TI - Persistent undeveloped mesonephric duct (a case report). AB - The mesonephric duct may fail to develop, resulting in congenital absence of the kidney and ureter. A unique case of persistence of the mesonephric duct without development into the kidney and ureter is presented. PMID- 2097362 TI - Evaluation of penfluridol in hospitalised chronic schizophrenic. AB - Thirty chronic schizophrenic patients completed 12 week treatment with a single weekly dose of 20 mg penfluridol, a new long acting oral neuroleptic. The patients were evaluated by using modified rating scale. Significant reduction in scores was demonstrated in 15 out of 26 symptom variables. Few side effects were reported which were easily controlled by conventional antiparkinson agents. Laboratory investigations remained within normal limits. PMID- 2097361 TI - Opponensplasty--an experience of twenty-three cases using three techniques. AB - Twenty-three opponensplasties were performed in 21 subjects. Flexor sublimis transfer was carried out in 15 hands, brachioradialis transfer in 4 hands, Makin's translocation of flexor pollicis longus in 2 hands and our modification of Makin's procedure in 2. The results were graded as excellent in 13 hands, good in 6 hands, fair in 3 hands and poor in 1 hand. Further, the power of pinch was graded as good in 14 hands, fair in 7 hands and poor in 2 hands. We suggest that it is almost always possible to devise an appropriate procedure to restore the opposition of the thumb. PMID- 2097363 TI - Predictive value of the nonreactive nonstress test in evaluating neonatal outcome. AB - High-risk pregnancies were followed up with antepartum foetal heart testing, in terms of perinatal mortality, Apgar score and incidence of caesarian section for foetal distress to look for the significance of a nonreactive nonstress test in 143 cases. The mean sensitivity was 65.64%, mean positive predictive value was 23.12%, and mean false positive rate was 76.87% for the nonreactive test results. PMID- 2097364 TI - Primary lupus vulgaris of the pharynx (a case report). PMID- 2097365 TI - Congenital hernia through the foramen of Morgagni (a case report). PMID- 2097366 TI - Neuralgic amyotrophy: a long term follow-up of four cases. AB - Neuralgic amyotrophy or brachial plexus neuralgia is a condition of uncertain etiology. It needs to be differentiated from the usual brachial plexus injuries. Nerves outside the plexus especially the spinal accessory nerve are involved. Neuralgia is also a feature. Four cases were followed-up in detail over a period of two years. The condition usually resolves almost completely on its own. PMID- 2097368 TI - Ileal endometriosis (a case report). AB - A case of endometriosis involving small bowel is reported here. It is the first case reported at our institution in the last 10 years period. PMID- 2097367 TI - Management of a case of lagophthalmos by Gillies' method (a case report). AB - A case of facial palsy with lagophthalmos with exposure keratitis was corrected surgically by a method of temporalis transfer. When the slings were tightened leaving 1 cm gap in the palpebral aperture, lagophthalmos persisted. A secondary tightening procedure causing overlap of the upper lid over the lower yielded good results. PMID- 2097369 TI - Impedance plethysmography: basic principles. AB - Impedance Plethysmography technique has been discussed with explanation of two compartment model and parallel conductor theory for the estimation of peripheral blood flow and stroke volume. Various methods for signal enhancement to facilitate computation of blood flow are briefly described. Source of error in the estimation of peripheral blood flow is identified and the correction has been suggested. PMID- 2097370 TI - Technical aspects of impedance plethysmography. AB - This paper describes the basic methods for measurement of body impedance, electrodes and their configuration, and the measuring instrument with its limitations. A microcomputer assisted impedance plethysmograph system, developed at BARC and different lead configurations for impedance plethysmographic investigation are also described. Typical impedance plethysmographic waveforms recorded from a normal subject and measurement of their amplitude and various time intervals are illustrated. PMID- 2097371 TI - Physiological correlates of impedance plethysmographic waveform. AB - A review of investigations into the origin of impedance plethysmographic waveform is presented in this article. Attempts made by several investigators in the comparison of impedance plethysmographic estimations of peripheral blood flow with that obtained by standard methods are briefly described. Investigations indicating the negligible contribution from contact impedance at body electrode interface are highlighted. Temporal correlation of impedance plethysmographic waveform recorded from thorax with various important events of the cardiac cycle is summarised and various hypotheses on the genesis of this waveform are presented. PMID- 2097372 TI - Diagnosis of aortic occlusive diseases using impedance plethysmography. AB - Impedance plethysmographic observations have been correlated with aortographic observations in 57 patients suspected of aortic occlusive diseases. Aortic occlusions have been characterised by marked decrease in blood flow index and significant increase in differential pulse arrival time at thigh level bilaterally. Atherosclerotic affection of the aorta has been featured by a bilateral decrease in the value of blood flow index as well as differential pulse arrival time at thigh level. Leriche's syndrome, however, has been found to decrease the blood flow index moderately at thigh in both the legs without any significant change in differential pulse arrival time. Aortography in all the patients has confirmed the diagnosis made by impedance plethysmography. PMID- 2097373 TI - Clinical and mycological spectrum of cutaneous candidiasis in Bombay. AB - A total of 150 patients with cutaneous candidiasis were studied. A detailed clinical history was taken. Scrapings were examined in 10% KOH, and the material cultured on Sabouraud's agar. Species were identified by the serum germ tube test, sugar fermentation and sugar assimilation tests. Of 150 patients 79 were females. The commonest presentation was intertrigo (75), vulvovaginitis (19) and paronychia (17). A history of chronic exposure to water was obtained in 94 cases, all had erosio interdigitalis blastomycetica and/or paronychia. Diabetes melltius as a predisposing factor was observed in 22 patients. The 10 cases of balanoposthitis had associated diabetes mellitus. Smear and culture were positive in all the patients. C. albicans was isolated in 136 cases, C. tropicalis in 12, and C. guillermondi in 2. The cultures of C. albicans had positive serum germ tube test. The 6 patients in the paediatric age group having perianal/genital involvement had a stools culture positive for C. albicans. PMID- 2097374 TI - Hashimoto's thyroiditis--a clinical review. AB - Hashimoto's thyroiditis constituted 5.15% of total thyroid disorders examined from January 1983 to July 1987. Females were predominant sufferers. Average age of patients was 41.14 years. Functionally 10 patients were euthyroid, while hyperthyroidism was present in 4 cases. Its preoperative diagnosis was not possible in any of the case. All patients were subjected to surgery and postoperative thyroxine supplement. PMID- 2097375 TI - Effect of Asparagus racemosus (Shatavari) on gastric emptying time in normal healthy volunteers. AB - Asparagus racemosus (Shatavari) is used in Ayurveda for dyspepsia (amlapitta) and as a galactogogue. It was hence compared with a modern drug, metoclopramide, which is used in dyspepsia to reduce gastric emptying time. Gastric emptying half time (GE t1/2) was studied in 8 healthy male volunteers using a cross-over design. The basal GE t1/2 in volunteers was 159.9 +/- 45.9 min (mean +/- SD) which was reduced to 101 +/- 40.8 min by Shatavari (p less than 0.001) and to 85.3 +/- 21.9 by metoclopramide (p less than 0.001). Metoclopramide and Shatavari did not differ significantly in their effects. PMID- 2097376 TI - Induction of heat shock (stress) genes in the mammalian brain by hyperthermia and other traumatic events: a current perspective. AB - Is the heat shock response physiologically relevant? For example, following hyperthermia or ischemia, what neural cell types show induction of heat shock genes and what is the time course of the effect? Initial experiments in this area demonstrated the prominent induction of a 70 kDa heat shock protein (hsp70) when labeled brain proteins isolated from hyperthermic animals were analyzed. Recently, in situ hybridization and immunocytochemistry have been utilized to map out the pattern of expression of both constitutively expressed and stress inducible members of the hsp70 multigene family. Different types of neural trauma have been found to induce characteristic cellular responses in the mammalian brain with regard to the type of brain cell that responds by inducing hsp70 and the timing of the induction response. Fever-like temperature causes a dramatic induction of hsp70 mRNA within 1 hr in fiber tracts of the forebrain and cerebellum, a pattern consistent with a strong glial response to heat shock. Tissue injury, namely, a small surgical cut in the cerebral cortex, induces a rapid and highly localized induction of hsp70 mRNA in cells proximal to the injury site. Using an immunocytochemical approach, a neuronal pattern of induction of hsp70 has been demonstrated following ischemia or kainic acid induced seizures. It is apparent that the pattern of induction of hsp70 may be a useful early marker of cellular injury and may identify previously unrecognized areas of vulnerability in the nervous system. PMID- 2097377 TI - Specific antibodies for tyrosinated and detyrosinated tubulin recognize retina tubulin subpopulations that do not participate in the posttranslational tyrosination/detyrosination cycle. AB - We have used the monoclonal YL 1/2 (Tyr antibody) and polyclonal (Glu antibody) antibodies, specific for tyrosinated and detyrosinated tubulin, respectively, to determine the levels and cellular distribution of these tubulin species in chick retina during development. At embryonic day 4, detyrosinated tubulin was restricted to the ganglion cells of the fundic region. As development progresses, immunofluorescence also appears, first, in the outermost zone of the retina and then in the plexiform layers. The Tyr antibody staining was found in the different layers and it was fairly homogeneous in distribution. Analysis by dot immunobinding showed that the ratios of tyrosinated to detyrosinated tubulin obtained at different ages do not agree with those obtained previously by an enzymatic method based on the incorporation of [14C]tyrosine. We found that the lack of coincidence is due to the fact that a fraction of the tubulin species determined by the Tyr and Glu antibodies does not participate in the posttranslational tyrosination/detyrosination cycle. This is a novel concept that should be considered in the interpretations of immunofluorescence studies concerning the cellular distribution of tyrosinated and detyrosinated tubulin. PMID- 2097378 TI - Rat facial motoneurons express increased levels of calcitonin gene-related peptide mRNA in response to axotomy. AB - The expression and localization of the mRNA encoding the calcitonin gene-related peptide (CGRP) were analyzed in the rat facial nucleus after axotomy by Northern blot analysis and by in situ hybridization histochemistry (ISH) using a synthetic 32P-labeled oligonucleotide probe. Northern blot analysis revealed the presence of the 1.2 kb CGRP mRNA in RNA extracted from the facial nucleus. This mRNA species was strongly increased after axotomy of the facial nerve. By ISH increased levels of CGRP mRNA were observed as soon as 16 hr after axotomy compared with the unoperated nucleus. CGRP mRNA could be localized in more than 50% of the motoneurons. Three populations of motoneurons with no, moderate, or strong labeling for CGRP mRNA could be distinguished. Peak expression of CGRP mRNA during the first 48 hr was followed by a decline to moderate levels at day 4 after lesion, and to almost basal levels at days 7 and 9. These data demonstrate that axotomy of the facial nerve leads to an early and strong induction of CGRP gene expression in motoneurons of the facial nucleus. PMID- 2097379 TI - Nicotinic acetylcholine receptor subtypes in human frontal cortex: changes in Alzheimer's disease. AB - Molecular genetic and pharmacological studies have suggested that several subtypes of nicotinic acetylcholine receptors exist in the mammalian and avian brain. Combining 3H-(-)-nicotine, 125I-alpha-bungarotoxin, and 125I-kappa bungarotoxin as ligands, we report here the first evidence for the existence in human frontal cortex of at least three different subtypes of nicotinic receptors. Autoradiographic analysis shows that specific 125I-kappa-bungarotoxin binding sites are concentrated mainly in several cortical layers. We also show that kappa bungarotoxin, but not alpha-bungarotoxin decreases the evoked release of 3H acetylcholine in rat cortical slices, indicating a likely presynaptic localization for some of the alpha-bungarotoxin-insensitive kappa-bungarotoxin sites in mammalian brain. The brains of patients with Alzheimer's disease show marked decreases in Bmax values for low-affinity 125I-kappa-bungarotoxin sites and both high- and low-affinity 3H-nicotine sites, whereas 125I-alpha bungarotoxin sites are not significantly different in number from age-matched control brains. We conclude that Alzheimer's disease does not affect all subtypes of nicotinic receptors in the frontal cortex to the same extent. PMID- 2097380 TI - Type II glucocorticoid receptors are expressed in oligodendrocytes and astrocytes. AB - Glucocorticoid hormones affect gene expression directly at the level of transcription via intracellular receptors that translocate to the nucleus in the presence of steroid. In the brain, two types of high-affinity receptors bind glucocorticoids, the type I, mineralocorticoid receptor and the type II, glucocorticoid receptor (GR). Both receptor types are expressed by many types of neurons. Although binding studies have suggested that glial cells may also express receptors, the expression of these receptors in specific classes of glia has not been studied previously. This immunocytochemical study was undertaken to determine which of the different classes of glial cells express type II GR. Primary cultures of mixed glial cells from rat cerebrum and cerebellum, purified oligodendrocytes and astrocytes, as well as two glial tumor cell lines were screened for the expression of glucocorticoid receptors using a mouse monoclonal antibody directed against rat liver GR (BuGR-2). Glial cell types were identified by morphology and immunoreactivity (IR) with antibodies directed against glial fibrillary acidic protein (GFAP), cyclic nucleotide phosphodiesterase (CNP), or myelin basic protein (MBP). Double immunofluorescence microscopy revealed that all GFAP-IR cells (type 1 and type 2 astrocytes), all CNP- or MBP-IR cells (oligodendrocytes), as well as immature and intermediate cell types expressed GR, although at different levels. C6 glioma and JScl1 Schwannoma cells were observed to express moderate to high levels of GR. Furthermore, cells grown in the absence of glucocorticoids had diffuse GR staining over the cytoplasm, whereas cells grown in the presence of the synthetic glucocorticoid dexamethasone had strong nuclear staining. These results demonstrate that, in vitro, all classes of glial cells express glucocorticoid receptors that can translocate to the nucleus in the presence of hormone. These observations suggest that glial cells are major targets for glucocorticoid-directed control of gene transcription in the nervous system. PMID- 2097381 TI - Glass micro-fibers: a model system for study of early events in myelination. AB - A system was developed to analyze early events in the process of myelination. Primary cultures of rat oligodendrocytes were maintained in the presence of glass micro-fibers which served as artificial axons. A culture chamber was constructed which allowed the close apposition of fibers and cells in a three-dimensional arrangement designed to resemble an in vivo environment. Cells cultured in the presence of glass micro-fibers coated with a glial cell matrix extract were induced to organize into clusters around the fibers. Examination of oligodendrocyte-fiber sandwiches by SEM revealed the presence of a number of cell contacts with the fibers. TEM images showed that, in most cases, fibers were surrounded by the cells and not multiply wrapped. Only occasionally was a loose wrapping of cell membrane observed around the fibers. Cells cultured in the presence of matrix-coated glass micro-fibers showed an increased production of sulfolipids that was at least partially dependent on the presence of the matrix coating. Coating of these "artificial axons" may aid in the identification of signal molecules produced by neurons which enable them to be myelinated. PMID- 2097383 TI - [Calcium antagonists in cardiological practice]. PMID- 2097382 TI - Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules. AB - During central nervous system (CNS) development, glial precursors proliferate in subventricular zones and then migrate throughout the CNS to adopt their final destinations and differentiate into various types of mature glial cells. Although several growth factors promoting the proliferation and/or differentiation of glial precursors have been identified, very little is known about the nature of signals that guide glial cell migration in the CNS. Therefore, we have investigated whether polypeptide growth factors and/or extracellular matrix molecules may mediate the migration of two major glial cell types, type 1 astrocytes and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells. We show that, in a microchemotaxis chamber assay, type 1 astrocytes move toward laminin and complement-derived C5a. Astrocyte migration toward laminin is inhibited by a laminin-specific pentapeptide, YIGSR-NH2. In contrast, O-2A progenitors migrate toward platelet-derived growth factor (PDGF), which also functions as a mitogen for these cells. Using a new method to simultaneously assay migration and DNA synthesis, we also demonstrate that O-2A progenitors can migrate toward PDGF even when DNA replication is inhibited with an antimitotic agent. Thus, migration of different types of glial cells can be induced in vitro by specific signaling molecules, which are present in the developing brain and may stimulate migration of glial cells prior to CNS myelination. PMID- 2097384 TI - [Diastolic mitral regurgitation in a patient with associated mitral valve defect caused by systemic scleroderma]. PMID- 2097385 TI - [Trans-esophageal electric cardiac stimulation in the diagnosis and treatment of arrhythmia (II)]. PMID- 2097386 TI - [Chronopharmacodynamics of delayed-action cardiac glycosides and nitrates]. AB - In 96 patients with coronary heart disease and stage II circulatory failure, the chronopharmacodynamics of strophanthin, corglycon, and nitrosorbide was studied by using acute clinical and pharmacological tests in the morning (8.00 a.m.), in the afternoon (2.00 p.m.), and in the evening (8.00 p.m.). Central and peripheral hemodynamic parameters were measured prior to and following 5, 15, 30, 60, and 120 min of intravenous injection of cardiac glycosides or sublingual administration of nitrosorbide in a dose of 10 mg for 240 min. The investigations showed that there were the most profound hemodynamic changes in the morning if strophanthin was used and in the afternoon if corglycon was given. The maximal reduction in heart pre- and afterload was seen in the morning when nitrosorbide was applied, the most improvement in central hemodynamic parameters was observed in the evening when nitrosorbide was used. PMID- 2097387 TI - [Use of prazosin in the treatment of heart failure in patients with post infarction cardiosclerosis]. AB - The study was undertaken to examine the effects of prazosin on clinical manifestations of the disease, hemodynamic parameters and myocardial contractility in 33 patients with coronary heart disease, postinfarction cardiosclerosis. The study was performed during an acute and chronic drug test. The efficiency of the therapy was checked by conventional clinical tools and examination of hemodynamic parameters and myocardial contractility from echocardiographic evidence. In the acute and chronic drug test, prazosin was found to cause a significant reduction in systemic and pulmonary pressures, total peripheral resistance and an improvement of total and regional myocardial contractility. Its two- or three-week therapy suffices to achieve the steady therapeutic effect of the drug. PMID- 2097388 TI - [Effect of bezamidine on plasma cholesterol and triglyceride levels in patients with familial hyperlipoproteinemia]. AB - The hypolipidemic agent bezamidine, a fibroic acid derivative (KPKA, Yugoslavia), was applied to treat Types 2a, 2b, 4 and 5 familial hyperlipoproteinemias. The highest reduction in plasma cholesterol and triglyceride concentrations was found in patients with Types 2b, 4 and 5 familial hyperlipoproteinemias. No clear-cut adverse effects of the drug were found during 3 months. PMID- 2097389 TI - [Study of the relations between prazosin administration schedule for patients with subacute myocardial infarction and the type of central hemodynamics based on pharmacokinetic data]. AB - The model-independent pharmacokinetics and hemodynamics were studied in 48 patients (35 males and 13 females; mean age, 60.0 +/- 1.3 years) with primary myocardial infarction of various sites. After a single dose of 2-5 mg prazosin, the mean prazosin molecule retention time, systemic clearance and distribution were found to be substantially different from those in the groups formed by the central hemodynamic types recorded before the drug administration. The interval between the maintenance doses was recommended to be 8 hours for the hypokinetic type, 7 hours for the hypovolemic type and 6 hours for the congestive and eukinetic types. In the models with "saturated" effects it was calculated that the optimal therapeutic effect of prazosin in patients with myocardial infarction was seen in the plasma concentration range of 50-80-100 ng/ml, whose attainment required its single dose of 3-5 mg 3-4 times a day during its course monotherapy. PMID- 2097390 TI - [Prognosis of the outcome of myocardial infarction by using early dynamic exercise tests]. AB - A total of 158 males with a history of myocardial infarction were examined. The examination involved collection of information on their histories, course of the disease and symptoms in the hospital period and early (mean, on day 13) bicycle ergometric exercise tests. A multifactorial analysis made it possible to derive the decision rule to predict the condition of a patient within the first year following the onset of myocardial infarction, which involved prognostically unfavorable history data, such as disability prior to myocardial infarction, alcohol usage, exertional anginal hospital-stage parameters, such as bradycardia, premature contraction, circulatory failure, nodal rhythm, as well as 1 mm or more of ST-segment elevation during the early bicycle ergometric exercise test. The sensitivity of the predictive rule developed was 88.5%, its specificity was 78.5%. The study shows that it is impossible to successfully solve the problem in attempting to predict the outcome from some parameters, including the bicycle ergometric test findings. It is possible to do so only when the complex of data on a patient is taken into account. PMID- 2097391 TI - [Constant-frequency trans-esophageal electric atrial stimulation for evaluation of the severity of illness in patients with stenocardia and the anti-angina effect of erinit]. AB - Constant-frequency transesophageal atrial pacing was used in 87 patients with coronary heart disease concurrent with stable angina pectoris of various functional classes (I-IV). This technique, as a bicycle ergometric test, allows one to assess the functional class of patients with angina and to ascertain the antianginal effect of agents, which was exemplified by erinit given in doses of 80 and 120 mg. PMID- 2097392 TI - [Characteristics of dilzem treatment of patients with ischemic heart disease]. AB - In 47 patients with coronary heart disease, the function of platelet was studied and ECG ST-segment was monitored. It was found that lower platelet function was more common in patients with severe coronary heart disease if they had long episodes of transient myocardial ischemia. Following 12 days of dilzem monotherapy, the most marked ++anti-ischemic and antianginal effects were observed in patients who had had higher platelet function. PMID- 2097393 TI - [Effect of 4-week metoprolol treatment on clinical manifestations and cardiac hemodynamics in patients with ischemic heart disease]. AB - Metoprolol was examined for its effects on clinical manifestations of the disease, peripheral hemodynamic and myocardial contractile parameters in 46 patients with coronary heart disease. The examination was performed during an acute drug test and continuous treatment for 4 weeks. The efficiency of the therapy was monitored by conventional clinical tools, bicycle ergometric test, studies of intracardiac hemodynamic parameters from echocardiographic evidence. With metoprolol, its antianginal effect was attained in 67.5% of the patients, there were significant antihypertensive and negative chronotropic effects and moderate cardiodepressive action. PMID- 2097395 TI - [Indications for cerebral revascularization through the system of the external carotid artery]. AB - The paper analyzes the study into the specific features of cerebral hemodynamics in patients with internal carotid artery occlusion. The study was performed by using Doppler ultrasound techniques. It revealed three different types of collateral blood flow of the brain according to the function of orbital anastomosis. The authors propose a new unique assessment of indications for a reconstructive operation on the external carotid artery for brain revascularization. The criteria proposed by the authors for assessing the cerebral hemodynamics enable the clear-cut indications for the above operation to be defined. The paper also summarizes the experience in examining and surgically managing 38 patients with internal carotid artery occlusion, who underwent revascularization of 39 channels of the external carotid artery. PMID- 2097394 TI - [Indications for using a method of pulsed therapy with cyclophosphamide and 6 methylprednisolone in patients with nonspecific aortoarteritis in the acute and subacute stages]. PMID- 2097396 TI - [Surgical tactics in arteriovenous dysplasias in relation to the site and extent of the lesion]. AB - Current procedures (venous occlusive plethysmography, Doppler ultrasound echocardiography, transcutaneous oxygen tension determination and computed tomography) for examining patients allow one to clarify the nature, extent, site, and features of anatomic relationships between the intact tissues and angiodysplasia-afflicted areas, to substantially facilitate the choice of surgical management of such patients. Application of current procedures for anesthesiological protection of the patients with the use of hemodilution, drug controlled hypotension, as well as the patient's autoblood during the operation ensures a radical intervention provided that the surgical concept is based on stepped therapy by using the endovascular occlusion techniques and following the due dates of each intervention stage. PMID- 2097397 TI - [Effect of indapamide preparations on myocardial contractility and hemodynamics in patients with hypertension]. AB - The hemodynamics and myocardial contractility were studied in 64 patients with Stages I-II hypertensive disease during 12-week monotherapy with indapamide agents (Fludex, Arifon, Lorvas). Their antihypertensive effect occurred 7-8 days later, with its peak at week 4, and was recorded in 64% patients, by normalizing the above parameters in 48% who had mainly lower or normal ejection and higher peripheral resistance. Improvement of hemodynamic and myocardial contractile parameters was parallel to a reduction in blood pressure. PMID- 2097398 TI - [Radionuclide ventriculography in the evaluation of left-ventricular function in patients with arterial hypertension]. AB - Systemic and intracardiac hemodynamic parameters were examined in 29 patients with arterial hypertension by radionuclide ventriculography. No impairments were found in resting left ventricular pump function in the patients. Left ventricular diastolic function exhibited 24 and 34.5% reductions in left ventricular filling rate and its peak filling rate, respectively, as well as a 44.8% increase in peak filling rate time. To assess the potentialities of myocardial adaptation to a postoperative decrease in blood pressure, artificial hypotension test by using the antihypertensive agent naniprus was performed in 15 patients. This test identified a group of patients with pronounced left ventricular diastolic dysfunctions who required a goal-oriented preoperative preparation. It also defined the principles of this preparation. PMID- 2097399 TI - [Comparative study of hypotensive effects of foridon and corinfar (results of the single-blind placebo-controlled study)]. PMID- 2097400 TI - [Use of peripheral vasodilator agents corbaton and corinfar combined with digoxin in patients with congestive heart failure of rheumatic etiology]. PMID- 2097401 TI - [The role of septic endocarditis in the development of functional disorders of heart valve prostheses]. PMID- 2097402 TI - [Variants of hemodynamic reactions to the calcium antagonist finoptin in patients with hypertension]. PMID- 2097403 TI - [Diurnal fluctuations of plasma renin activity and aldosterone level in patients with arterial hypertension]. PMID- 2097404 TI - [Glucocorticoid function of the adrenal cortex in patients with myocardial infarction: diurnal rhythms of plasma glucocorticoid levels]. PMID- 2097405 TI - [Indicators of gas exchange and physical work capacity of patients with initial symptoms of ischemic heart disease]. PMID- 2097406 TI - [Characteristics of central hemodynamics and autonomic regulation of cardiac rhythm at rest and after meals in patients with ischemic heart disease associated with duodenal ulcer]. PMID- 2097407 TI - [Effect of meteorological factors on the development of myocardial infarction]. PMID- 2097409 TI - [A case of intravital diagnosis of bilateral pulmonary artery aneurysm]. PMID- 2097408 TI - [Low-energy transvenous cardioversion in recurrent ventricular tachycardia in the acute period of myocardial infarction]. PMID- 2097410 TI - [Laser correction of arrhythmia]. PMID- 2097411 TI - [The role of spasm in the pathogenesis of stenocardia]. PMID- 2097412 TI - [Mitral valve prolapse]. PMID- 2097413 TI - [Episodes of palpitations and the changes in the configuration of the QRST complex]. PMID- 2097414 TI - [Clinical aspects and diagnosis of infectious endocarditis]. PMID- 2097415 TI - [Retroperitoneal and pelvic-presacral teratogenic tumors in early childhood--the diagnostic and surgical treatment problems]. AB - Teratogenic tumors are characteristic for childhood. For a period of 15 years the authors have observed 12 children with retroperitoneal and pelvic-presacral localization of teratogenic tumors. They were most common in girls under one year of age. The clinical symptoms, the methods applied for diagnosis are analysed; the diagnostic importance of rectal digital examination, inferior venacavography and especially of computer tomography is emphasized. Radical removal of the tumor was performed in 11 children and biopsy in 1. The most convenient operative access to pelvic-presacral-retroperitoneal tumors is a one-step double access (abdomino-sacrococcygeal). As a result of complex treatment--surgical and chemotherapy--the postoperative results were good in 9 children. PMID- 2097416 TI - [Transduodenal papillosphincteroplasty in the treatment of benign diseases of the terminal choledochus and papilla Vateri]. AB - The modern state of the problem and the indications and contraindications for performing transduodenal papillosphincteroplasty are discussed. Personal experience is recorded with 67 transduodenal papillosphincteroplasties, performed for the period 1983-1989, against the background of 1091 operations on the hepatobiliary system, 171 of them on the extrahepatic bile ducts, performed during the same period. Proceeding from their own experience and from available data in the literature, the authors analyse and evaluate the surgical and nonsurgical methods of treatment of benign diseases of the terminal common bile duct and the duodenal papilla, manifested by stenotic lesions. The most important indications and contraindications for applying the different therapeutic methods are adduced. Remarks are made on the technique, which is of major practical importance and the respective conclusion is substantiated. PMID- 2097417 TI - [The remnant cystic duct in the syndromal complex of the postcholecystectomy syndrome]. AB - Some modern aspects of the postcholecystectomy syndrome and the importance of d. cysticus remnant for its arising are discussed. Analysis is made of 13 patients with postcholecystectomy syndrome surgically treated at the Department of Propedeutics of Surgical Diseases, Research Institute of Surgery, over the period 1983-1989. Results are reported of a study of 180 operated patients (cholecystectomized), in in 7.8 of whom low-grade postcholecystectomy syndrome developed. Accent is laid on the importance of the intraoperative diagnosis and on some characteristics of technical nature, requiring precision in processing d. cysticus. Conclusion is drawn, aimed at reducing to a minimum the percentage of postcholecystectomy syndrome. PMID- 2097419 TI - [Echinococcosis of the heart]. AB - From 1971 through 1987 six patients with echinococcus of the hear have been operated. In four of them the hydatid cyst was localized in the right portion of the heart and in two in the left ventricle. Left thoracotomy was used for the operation of the former four patients, whereas the hydatid cysts localized in the left ventricle were operated under bypass circulation. None of the operated patients died. The diagnosis was established by using computer tomography, which provided exact localization of the hydatid cyst and determined the operative approach. Echinococcosis of the heart is rare and creates diagnostic difficulties. This diagnosis is an absolute indication for operative intervention which under contemporary conditions should be performed by use of bypass circulation. PMID- 2097421 TI - [Congenital anomalies of the coronary arteries]. AB - Two patients with congenital anomalies of the coronary arteries were operated. One them had aneurysm of the Valsalva sinus and anomalous drainage of the right coronary into the right ventricle with 60 per cent arterio-venous shunt. The second had angiodysplastic-type anomaly of the left coronary artery. Both patients were operated on functioning heart, using II-shaped sutures through teflone appliances. However rare, congenital anomalies of the coronary arteries raise diagnostic difficulties. Exact diagnosis is feasible only after coronarography which determines also the type of operative intervention. The operation should preferably be made under bypass circulation. PMID- 2097418 TI - [Surgery and AIDS]. PMID- 2097420 TI - [The diagnostic difficulties in multiple tumors of the urothelium]. AB - Early diagnosis of all the foci in multiple urothelial tumors keeps on being difficult. On comparison of the clinical and postmortem diagnosis the tumor of the renal pelvis remains unrecognized in about 31 per cent of the cases and the tumor in the ureter in more than 50 per cent. A case is reported of primary multiple urothelial tumor, for whose diagnosis all modern methods were used. In spite of all this, the focus in the renal pelvis was diagnosed four years after the onset of clinical manifestations of the disease. In this connection, the possibilities of the different methods of examination are discussed. PMID- 2097422 TI - [Percutaneous cholecystectomy and litholysis with methyl tert-butyl ether under ultrasonic control]. AB - The first percutaneous cholecystostomies under ultrasound control with therapeutic purpose, performed in Bulgaria, are reported. They furnish the opportunity for local treatment of acute cholecystitis and chemical litholysis in biliary calculosis. Control of the latter was realized by microscopic determination of the amount of cholesterine crystals in periodically aspirated bile. Indications for this procedure are defined after thorough discussion by internist and surgeon. Transhepatic approach and long-term treatment with methyltertiary-butyl ether are considered obligatory. PMID- 2097423 TI - [Arterial hypertension following kidney transplantation in patients on conventional immunosuppressive therapy and in those on cyclosporin A]. AB - The incidence and causes of arterial hypertension following 110 kidney transplantations in 109 patients were studied. Seventy-five patients with satisfactory renal function were observed over a period of more than a year. Of these, 46 + 2 patients received Azathioprin and 27 of them had arterial hypertension; of the 29 + 5 patients who received cyclosporin A, 18 had arterial hypertension. The incidence of hypertension and its levels were significantly higher in Azathioprin treated patients, than those on cyclosporin A treatment. Slight counter relation between arterial hypertension and blood cyclosporin A level was found. Arterial hypertension reached peak values during the first month with slight decrease on the third month, followed by further elevation. The basic reasons for arterial hypertension were rejection reactions, the own kidneys left in situ and arterial stenosis of the grafted kidney. PMID- 2097424 TI - [The risk factors and course of acute cholecystitis in youth]. PMID- 2097425 TI - [Lord's operation in the treatment of idiopathic hydrocele]. AB - In spite of observing the requirements for thorough hemostasis and minimal trauma, the routine methods applied so far for treatment of idiopathic hydrocele have shown high percentage of postoperative complications. In a search for a more reliable and atraumatic operative method, since November 1988 the authors have performed operative treatment in 14 patients by the method of Lord. The operative technique is presented and the first results reported. Although the early results were good, for an overall appraisal of the possibilities of this method it will be necessary to gain more experience and then make comparative assessment with the routine methods applied thus far. PMID- 2097426 TI - [The postcholecystectomy syndrome in youth]. PMID- 2097427 TI - [The potentials of intrarectal echography for the preoperative staging and postoperative follow-up of rectal cancer]. AB - The method is reported of intrarectal echography and the ultrasound changes of the rectal wall in cancer. The report is based on experience with 38 patients. The basic criteria for preoperative grading of rectal cancer by the TNM system are determined and the diagnostic exactness of the method is discussed (89.5 per cent). The value of intrarectal echography in determining the extent of the surgical intervention and the postoperative control of the patients is debated. PMID- 2097428 TI - [The incidence of duodenogastric reflux and its relation to stomach and duodenal diseases]. AB - The data available in the literature on the incidence of duodenogastric reflux and its relation with diseases of the stomach and duodenum are controversial. A study was performed based on the results of 4256 primary endoscopies of the stomach and duodenum: 3673 in nonoperated patients and 583 in patients having undergone vagotomy and resection. For duodenogastric reflux one judged from the yellow coloration of the gastric juice and regurgitation of bile at the moment of examination. Reflux had 428 patients (10.05 per cent)--330 in the nonoperated group (8.98 per cent) and 98 in the operated group (16.81 per cent). Inference is drawn that duodenogastric reflux does not coincide in incidence with reflux gastritis and that causal relation might be searched between gastritis, reflux esophagitis and duodenitis, on the one hand, and duodenogastric reflux, on the other. PMID- 2097429 TI - [The surgical treatment of hemorrhoids. Their suturing ligation without excision]. AB - Analysis is made of the results of application of a modified method offered by the author "suturing ligature without excision" in hemorrhoids. It consists of suturing ligature of the vascular bundle, including ligation of the hemorrhoid node itself without excision. For the period 1981-1988 the method was applied on 32 patients. The results were compared with those in a control group of 105 patients operated by the method of Milligan, Morgan. The mean postoperative hospital treatment lasted 3.2 days, vs. 11.4 days in the control group. It was moreover characterized by minimal pain, good state of well-being and hygiene, normal intestinal passage from the first day with flatulence and defecation. Pain lasting more than 24 hours had only 2 patients, vs. 97 in the control group. There was no constrained retention of bowel movement, which in the control group led to difficult flatulence in 101 patients and exacerbation of colitic complaints. The method is pathogenetically substantiated. It provides ligation of the terminal branchings of a. rectalis sup. averts relapses and postoperative bleeding, preserves a sufficient mucosal surface to ensure the physiologic act of flatulence. PMID- 2097430 TI - [The surgical procedure in treating hemorrhoidal disease]. PMID- 2097431 TI - [Liposuction--the current potentials]. PMID- 2097432 TI - [Spontaneous internal biliary fistulae (their pathogenesis and pathological anatomy)]. PMID- 2097433 TI - [Closure of the double-barreled colostomy]. AB - In a survey of the literature the authors discuss the problem of double-barreled colostomy closure, which a remains controversial. The high percentage of postoperative complications--up to 50 per cent and mortality up to 2.1 per cent are responsible for nondetermination of the method of choice, depending on the type of colostomy, of the colostomy complications and the absence of indications for choice of the time of colostomy closure. PMID- 2097434 TI - [A case of a primary tumor of the ureter]. PMID- 2097435 TI - [A case report of Bouveret's syndrome]. PMID- 2097436 TI - [The results of using a new surgical method in carcinomas located in the proximal portion of the lower third of the rectum]. AB - A new type of abdomino-transanal resection of the rectum instead of its extirpation is being applied in tumors localized in the proximal part of the lower one third of rectum (5-6 cm from the anorectal line). For removing the whole lymph collector of the lower one third of the rectum the authors remove the levator tunnel as well. What remains intact is only the anal mucosa and the external anal sphincters. The anastomosis is realized by preliminary placing all catgut. Prophylactic transversostoma is also an obligatory procedure, so that the anal sphincters may remain at rest for 2-3 months after the operation. During this time the anal sphincters and the neorectum are fixed to the adjacent tissues and the anal tonus is fully restored. This operation was applied in 15 patients with very good result, as regards anal continence, without any case of relapse of the tumor so far. PMID- 2097437 TI - [The use of a new method for the restoration of duodenal passage following the partial extirpation of its wall in treating locally advanced tumors of the right half of the colon]. AB - When excision of the tumor infiltration of the duodenum is followed by formation of a small defect, the authors apply a personal modification of two-story suture. Then the duodenal suture is fully covered with the serosa of the small-intestinal loop. Thus the suture is hermetically sealed and remains in a relative rest. When a large defect remains after excision of the tumor infiltration of the duodenum, a short jejunal loop is taken and a longitudinal section is made on it of equal length with that of the duodenal defect. Laterolateral anastomosis is made between the duodenal defect and the jejunum. Brown's anastomosis is made somewhat distally from the duodenojejunostomy. In this way the duodenum is not narrowed, the tissues are sutured without any tension and postoperative duodenal stasis is minimal. The first variant of the method was applied in 3 patients and the second in 3 patients with very good postoperative result. PMID- 2097438 TI - [Incisions for an approach to the cervical segment of the thoracic duct]. AB - After a brief review of available data in the literature on the sections for surgical approach to the cervical segment of the thoracic duct, the authors made a comparative analysis, using time-honoured objective criteria on surgery, between the universal transverse cervical section (20 operated patients) for approach to the cervical segment of the thoracic duct and the oblique cervical section which they suggest (28 operated patients) it passes along the bisector of the angle formed between the thoracic pedicle of the sternocleidomastoid muscle and the upper edge of the left clavicle. It is concluded that the oblique cervical section for approach to the cervical segment of the thoracic duct is superior, with respect to accessibility and inflicted trauma. PMID- 2097439 TI - Hemodynamic changes in skin microcirculation induced by vibration stress in the conscious rabbit. AB - Cutaneous microcirculatory responses to vibration stress were observed by microphotoelectric plethysmography in a transparent round window installed in the ears of conscious rabbits. Vertical vibrations at frequencies ranging from 8 to 250 Hz were applied to the abdomen of the rabbits for 5 min. The vibrations produced an increase in heart rate and the index of discomfort, and a decrease in blood flow in the skin microcirculation. The maximum response was observed at 63 Hz. Rhythmic fluctuations in microcirculation were associated with two components: component A had a small amplitude and high frequency, and component B had a large amplitude and low frequency. Vibration exposure led to a large increase in component B and a smaller increase in component A. During vibration exposure, component A was suppressed by treatment with diltiazem, a calcium channel blocker, and was not affected by bunazosin, an alpha-1 adrenoceptor antagonist. The opposite changes were observed for component B. This indicates that components A and B of the rhythmic fluctuations are regulated by myogenic and neurogenic activities, respectively. Thus, the hemodynamic changes of skin microcirculation induced by vibration may actually be due to a neurogenic factor, especially sympathetic nerve activity. The responses appear to depend on the frequency of the vibrations. PMID- 2097440 TI - A clinical study of percutaneous nephroureterolithotripsy. AB - Percutaneous nephroureterolithotripsy was performed a total of 309 times in 225 renal units of 209 patients with upper urinary tract calculi, a mean of 1.37 times per kidney. Residual calculi, 5 mm or greater in diameter, were observed in 3 of 100 kidneys (3%) with single calculi, 12 of 102 kidneys (11.8%) with multiple calculi, and 8 of 23 kidneys (34.8%) with staghorn calculi. The number of sessions, duration of nephrostomy, and the frequency of residual calculi were significantly higher in problem calculi, such as multiple, large and staghorn calculi, than in other calculus types. A combination of percutaneous nephroureterolithotripsy and extracorporeal shock wave lithotripsy was considered to be necessary to improve the efficiency of lithotripsy. Complications included a transient fever, bleeding requiring transfusion and perforation of the renal pelvis in a small number of cases, but these were all mild and could be managed by conservative treatment, alone. PMID- 2097441 TI - Effects of anticonvulsants on the electroconvulsive threshold lowered by DA, 5-HT or GABA depletion. AB - A cannula was chronically implanted in the rat ventriculus, and anticonvulsants were administered through the cannula. The effects of the anticonvulsants applied, intraventricully, were investigated on the decreased electroconvulsive threshold induced by pretreatment with alpha-methyl-p-tyrosine (alpha-MT), p chlorophenylalanine (PCPA) or allylglycine. The TRH analog, DN-1417, valproate (VPA), and phenobarbital (PB) raised the electroconvulsive threshold which had been lowered by alpha-MT. The reduced electroconvulsive threshold from PCPA was raised by DN-1417, but not by VPA or PB. The allylglycine induced lowering of the electroconvulsive threshold was raised by VPA and PB, but not by DN-1417. Phenytoin had no anticonvulsant effect on rats pretreated with these drugs. From these results, it was concluded that the anticonvulsant action of DN-1417 could be due to enhancement of dopamine and/or serotonin turnover. PMID- 2097442 TI - Benign exertional headaches induced by swimming. AB - A 57 year-old woman with benign exertional headaches induced by swimming is described. The headaches were bilateral, throbbing and occurred while swimming. She had a history of occasional similar headaches while straining during bowel movements. The neurological examination and computed tomographic (CT) scanning were normal. The electroencephalogram (EEG) had diffuse alpha activity, and no symptoms or significant changes of the EEG were triggered by the Valsalva maneuver, which causes a transient increase in cranial blood pressure and alters the normal vascular balance. She has stopped swimming and since then has never had a headache. No medications were needed. This case demonstrates that not all headaches are triggered by intracranial lesions. Benign exertional headaches should also be considered in the differential diagnosis of this type of headache in the elderly. PMID- 2097443 TI - Clinical and pathological evaluation of early cancer in the gastric cardia. AB - We report 9 rare cases (7 males and 2 females) of early gastric cancer of the esophagogastric junction. From 1976 to 1988, 1308 cases of gastric cancer were resected in our Institute. Of these, 479 (36.6%) cases were early gastric cancer. Among all 479 early gastric cancers, 9 (1.9%) were located within 2 cm of the esophagogastric junction on the lesser curvature and/or posterior wall of the cardia. This represents 11.7% (9/77) of the cases of cancer at the esophagogastric junction. This incidence contrasts with the 39.5% of early cancers elsewhere in the stomach. Overall, 36.6% (479/1308) were early gastric cancer. Eight of these 9 patients were resected through the abdominal approach and one by the thoracoabdominal approach. Seven underwent proximal and 2 underwent total gastrectomy. On microscopic examination, one cancer was m-cancer, and 8 were sm-cancer. Lymphnode metastasis was found to be absent in all 9 cases. The prognosis of cancer of the cardia is generally poorer than that for adenocarcinoma in the corpus or distal stomach. However, cancer recurrence 22-91 months postoperatively was zero in these 9 cases of early gastric cancer at the esophagogastric junction. PMID- 2097444 TI - Retrospective studies of gastric cancer with hepatic metastases. AB - From 1979 to 1988, a total of 1265 cases of gastric cancer were admitted to our Institute. Of these, 80 cases (6.3%) involved hepatic metastasis. Thirty-eight cases (47.3%) underwent gastrectomy (24 distal, 2 proximal, 11 total and one partial). Of these 38 cases, 7 underwent a combined resection of a simultaneous metastatic hepatic tumor. A total of 19 (67.9%) of the 28 cases in H1, 6 (37.5%) of the 16 cases in H2, and 13 (36.1%) of the 36 cases in H3 underwent gastrectomy. Hepatic metastasis occurred most frequently (18.2%) in Borrmann type 1, 5% in type 2, 14.9% in type 3 and 8.7% in type 4. Of all 593 resected advanced cases, there were 283 differentiated type, with a hepatic metastasis rate of 14.5%, and 310 undifferentiated type with 7.1% rate of hepatic metastasis. In H1 and H2, the prognosis after primary gastric cancer resection was better than for unresected cases. Moreover, there have been reports recently of long-term survival using continuous hepatic arterial infusion of anti-cancer drugs, and of combined resection of the metastatic hepatic tumor after curative gastrectomy. Therefore we should not give up these H1 and H2 patients. PMID- 2097445 TI - Survival of rectal carcinoma patients studied with flow cytometric DNA analysis. AB - The cellular DNA content was measured with flow cytometry from paraffin-embedded materials in 197 patients with primary rectal cancer who had had "curative" resection. All patients were followed clinically for from 2.5 to 7 years. There was a significant difference in recurrent rate between DNA diploid and aneuploid tumors. The cumulative survival rate (Kaplan-Meier) of curative operative rectal carcinomas was worse in DNA aneuploid than in DNA diploid tumors (p less than 0.05). These data suggest that tumor DNA content is an important prognostic indicator for both recurrence and overall survival in patients with primary rectal carcinoma. PMID- 2097446 TI - Evaluation of the therapeutic effect of percutaneous nephroureterolithotomy by Tc 99m diethylenetiaminepentaacetic acid (DTPA) renal scintigraphy--alteration of the renal fraction of blood flow, split-GFR, and renal mean transit time. AB - To evaluate the therapeutic effects of percutaneous nephroureterolithotomy, the renal function of eleven patients with renal calculi was studied, pre- and post intervention. Renal function was determined, by renal scintigraphy with the renal agent, Tc-99m diethylenetriaminepentaacetic acid (DTPA). In each renal scintigram the renogram curve was analyzed and the following were determined by deconvolution analysis; the renal fraction of blood flow (RFBF), DTPA-glomerular filtration ratio (GFR), and the renal mean transit time (MTT). The successful results in percutaneous nephroureterolithotomy (PNL) was proven using the radionuclide technique in most cases. From these results it can be concluded that renal scintigraphy is an effective procedure to evaluate the effect of PNL for treating renal calculi and secondary hydronephrosis. PMID- 2097448 TI - The effects of 5-hydroxytryptamine on cat sympathetic preganglionic neurons in vitro. PMID- 2097447 TI - Congenital epulis--an electron microscopic observations of two cases. AB - Two cases of congenital epulis occurring in the gingiva at the site where the lower deciduous incisors were to erupt are described. The first patient was a 7 day-old female infant. Her epulis was diagnosed, histopathologically, as a granular cell tumor. Electron microscopy revealed that the tumor cells were large with small eccentric nuclei. The cells were filled with granular structures. These granular substances varied in size and electron density. Case 2 involved a 37 day-old male infant. A histopathological diagnosis of fibromatosis was made. Electron micrographs showed a proliferation of cells which resembled fibroblasts. These cells varied in shape, including some with thin, long processes. Abundant reticular and collagen fibers were present in the stroma. In both cases, the postoperative course was uneventful without recurrence. PMID- 2097449 TI - [The detection of hepatitis B virus DNA in nerve tissue: the procedural aspects]. AB - A patient with HBsAg-positive chronic aggressive hepatitis and HBeAg and hepatitis B virus DNA (HBV DNA) developed fatal Creutzfeldt-Jakob disease. The investigation of cerebrospinal fluid and a temporal lobe brain tissue post mortem sample with radioactive probes of previously cloned HBV DNA showed the unquestionable presence of viral nucleotide sequences in the nervous tissue (about 9 viral genomes per cell). Although a pathogenetic role in the underlying neurologic disease cannot be attributed to HBV, our observation widens the spectrum of tissues where HBV has been detected, and supports the contention that there are replicative extrahepatic foci where the immunologic system of the host is permissive for the virus. PMID- 2097451 TI - [The serum and intraerythrocyte concentration of ferritin in the anemia of rheumatoid arthritis]. AB - Serum concentration of ferritin (Ft) and its glycosylated fraction (Ft-Gl) and intraerythrocytic ferritin (Ft-e) concentration were measured in 26 patients with anemia and active rheumatoid arthritis. Patients were divided into 2 groups according to the presence of anemia of chronic diseases (n = 13) or associated ferropenia. Unlike the first group, patients with associated ferropenia had lower concentration of the above parameters than 31 control subjects. The logarithmic value of FT (log FT) directly correlated with globular sedimentation velocity. Ft Gl and log Ft-e correlated with transferrin saturation (r = 0.603, p less than 0.01 and r = 0.444, p less than 0.05). Log Ft-e also correlated with Ft (r = 0.504, p less than 0.01). The probability of ferropenia when Ft was 60 micrograms/l or lower was 0.91, and when Ft-e was 1.5 ag/cel or lower was 0.66. It is concluded that the ferropenic status in active rheumatoid anemia decreases the iron dependent synthesis of ferritin (Ft-Gl) more than that mediated by the acute phase response. The intraerythrocytic content is low due to the scanty iron supply to the erythroblast. Ft is more efficacious than Ft-e in the diagnosis of ferropenia. PMID- 2097450 TI - [The introduction of liquid oxygen as a portable source in continuous home oxygen therapy]. AB - The most widespread types of oxygen delivery at home in our area are bottles where the gas is stored under pressure and concentrators. Both devices can only be used at rest. We have assessed a new system for the delivery of liquid oxygen to be used at home, provided with a portable unit which permits that the patients receive oxygen also outside their homes. Seven such devices have been implemented in the Barcelona area, with an excellent acceptance and without technical problems. To verify the clinical indication, exercise tests were carried out both in baseline conditions and receiving oxygen from the portable source. Oxyhemoglobin saturation and the walked distance were continuously measured. In all patients important drops in the saturation of oxyhemoglobin were recorded during walking, which was corrected with oxygen administration. Liquid oxygen with a portable source is a good delivery system for oxygen therapy at home, permitting to receive oxygen throughout the day, particularly during exercise. Although the availability of liquid oxygen is limited, it should be recommended to the patients in whom exercise hypoxemia is shown to be corrected and who desire an active social life. PMID- 2097452 TI - [The extrahepatic localization of the hepatitis B virus]. PMID- 2097453 TI - [Dyslipidemias and the secondary prevention of arteriosclerosis]. PMID- 2097454 TI - [T lymphoblastic leukemia with leukemoid reaction or the extramedullary blast crisis of Philadelphia chromosome-negative chronic myeloid leukemia? Comments apropos 2 cases]. AB - Reactive leukocytosis has been reported in patients with non-Hodgkin's lymphoma of different histologic types. On the other hand, the blastic crisis of chronic myelocytic leukemia (CML) can sometimes be localized outside the bone marrow and simulate lymphoma, particularly when the blasts are of lymphoid lineage and the blastic crisis is the presenting feature of the disease. We report two patients in whom the differential diagnosis between lymphoblastic lymphoma with reactive leukocytosis and blastic crisis of CML outside the bone marrow was raised. They were two males aged 32 and 22 years, respectively, with lymphadenopathy (and one with splenomegaly), who were initially diagnosed of T lymphoblastic lymphoma. In both cases, leukocytosis was detected with myelemia and dysgranulopoiesis in the onset in one of them and when lymphadenopathy reappeared after remission in the other one. In addition, one patient had marked eosinophilia. In the bone marrow there was marked granulopoietic hyperplasia, with a reduction of fatty cells, and the granulocyte alkaline phosphatase index was reduced. However, the cytogenetic study did not disclose the existence of Philadelphia (Ph) chromosome, and bcr/abl molecular rearrangement was also not observed in the molecular study of both cases. We discuss the basic aspects of differential diagnosis between T lymphoblastic lymphoma with leukemoid reaction and T lymphoid lymphadenopathic blastic crisis of Ph-negative, bcr/abl-negative CML. PMID- 2097455 TI - [Notes on the organization of a congress]. PMID- 2097457 TI - [Integrins: the importance of cell adhesion]. PMID- 2097456 TI - [Clonidine-naltrexone: a new technic for the detoxification of opiate addicts]. PMID- 2097458 TI - [Massive hemoptysis secondary to an aortobronchial fistula: a rare complication of staphylococcal pneumonia]. PMID- 2097459 TI - [Cough associated with angiotensin-converting enzyme inhibitors]. PMID- 2097460 TI - [The limitation of joint movement in diabetes mellitus]. PMID- 2097461 TI - [Varicella complicated by acute pericarditis]. PMID- 2097462 TI - [Cholestatic jaundice as a form of presentation of miliary tuberculosis]. PMID- 2097463 TI - [Pyramidal and extrapyramidal involvement as a sequela of heat stroke]. PMID- 2097464 TI - [Respiratory symptoms and ventilatory capacity of sewage canal workers]. AB - Respiratory symptoms and ventilatory capacity were studied in a group of 70 subjects employed as sewage workers. It was found that exposed workers had an increase in the prevalence of chronic respiratory symptoms when compared with control workers, although the difference was statistically significant only for chest tightness (p less than 0.01). In exposed workers there was a high prevalence of acute symptoms which develop during the shift being particularly pronounced for eye irritation, dyspnea and cough. A large number of sewage workers complained of skin disorders. Results of lung function testing demonstrated reduction of FEV1, FEF50 and FEF25 in relation to predicted normal values suggesting obstructive changes mostly located in smaller airways. Our data confirm that sewage workers are exposed to different occupational noxious agents which may lead to the development of chronic lung function changes. PMID- 2097465 TI - Mycoplasmas, a review of surveys examining human genital infections and experimental infection in mice with special reference to in vitro fertilization. AB - Patients attending an "In Vitro Fertilization" clinic were shown to be commonly infected in the semen with Ureaplasma urealyticum (29%) and Mycoplasma hominis (12%). Other mycoplasmas were rarely recovered. M. hominis was not eradicated from sperm by washing, although washing removed 71% of the ureaplasmas from infected semen. There was a significantly higher incidence of U. urealyticum and M. hominis in patients with cervical intraepithelial neoplasia (P = less than 0.05 and P = less than 0.01 respectively) than in controls. The results showed a possible association of U. urealyticum and M. hominis with CIN type 3. Mouse experiments showed that M. pulmonis has an affinity for genital tissue, adhered to the surface of eggs and could penetrate the zona pellucida, but did not affect fertilization except where pus was present in the oviduct. PMID- 2097466 TI - [Familial cardiovascular risk factors]. AB - In a 16 per cent systematic sample of the fifth grade elementary school pupils from Split, Yugoslavia (198 boys and 250 girls, aged 11.3 +/- 0.4 years; mean +/- SD), 116 children (25,9% of the sample; 61 girls and 55 boys) were found at risk for cardiovascular diseases, having the values of one or more of the recognized risk factors above the 90th percentile of distribution for age and sex, e.g. serum cholesterol greater than 5.6 mmol/l. After the 3-year follow-up period the parents and the available relatives of these children were checked for the same risk factors in order to evaluate the magnitude of family aggregation. The prevalence of cardiovascular risk factors was 3-5 times higher for the parents of the children at risk than for the control parents (e.g. 57.1 vs 11.8 per cent in boys; p less than 0.001). The observed parent-child agreement was highest for serum cholesterol and triglycerides (range 30.0-37.5%; p less than 0.01). The family clustering of risk factors was prominent in the second generation (e.g. grandparents, p less than 0.01) as well, and even among the other relatives (p less than 0.05). It is concluded that the probability of adverse cardiovascular outcome increases not only with the individual level of aberration and with the mutual enhancement of risk factors, but with positive history and family aggregation as well: these phenomena have important influence on the process of physicians' decision making, with obvious practical implications. PMID- 2097467 TI - [Etiopathogenesis of varicosities of the lower extremities]. AB - To investigate the significance of heredity in the development of varicosities of the lower extremities, and to establish the association between the sclerotherapy and the pathologic changes of the perforating and deep veins as well as the share of trauma in the development of perforating venous insufficiency of the lower part of the leg, the author studied 484 hospitalized patients. By using modern diagnostic procedures, the pathologic changes of the venous system were identified and located and varicosities were classified into five groups. A positive family anamnesis was found in 64.5% of the treated patients. The relationship between the heredity and the pathologic changes of the venous system is shown in tables. Of all the treated patients, 12.2% underwent sclerotization before the admission to the hospital. In 50.8% of these patients, the author found pathologic changes of the perforating veins and in 22% pathologic changes of the deep veins, as well. Due to perforating venous insufficiency 135 patients were operated. Among these patients, 21.4% reported positive history of trauma, while in 14.1% of surgically treated patients some degenerative changes of the fatty-connective tissue of the crural fascia were found. This speaks in favour of the assumption that trauma of the lower extremities may lead to perforating venous insufficiency. PMID- 2097468 TI - [Mycetismus in children--report of an epidemic of poisoning]. AB - In the autumn of 1988 an outbreak of mushroom poisoning occurred in the surroundings of Zagreb. In less than 3 week period about 140 cases of poisoning were recorded, 17 of whom were children treated at the Department of Pediatrics. Nine children developed gastrointestinal and 18 phalloid syndrome. In the differential diagnosis of each gastroenterocolitis, mushroom poisoning should be taken into consideration, especially during warm and wet summer and autumn. The detection and identification of the poison is the main principle in diagnostics and medical treatment of each poisoning, thus of mushroom poisoning. Incriminated mushroom was identified in 21 of 27 patients (77.8%). Timely application of general therapeutic procedures, especially thorough gastric lavage in each patient, and application of plasmapheresis in case of Amanita phalloides poisoning have been found effective in reducing lethality and in rapid clinical recovery. Of the total number of 18 Amanita phalloides poisoned children, 4 died which is a lethality rate of 22%. In health education it should be pointed out that there are no simple methods for distinguishing edible mushrooms from poisonous ones. PMID- 2097469 TI - [Acquired renal cysts in patients on chronic hemodialysis treatment]. AB - The kidneys of chronic hemodialysis patients are subject to different morphological modifications, although they are in fact functional. One of those modifications, cystic transformation of the kidneys, is the object of this study. Seventy-nine chronic hemodialysis patients treated at the Hemodialysis Centre of the Osijek General Hospital underwent ultrasonographic examinations in 1987. Subsequently, the rest of 56 patients underwent scanning again. Only the group of patients that could be followed up for the two-year period was analysed. It has been noticed that the number of patients having cysts has been higher after some time (19 to 47), as well as of those having more than 3 cysts (2 to 8) and of those having bilateral cysts (4 of 19 to 37 of 47). The patients having more than 3 cysts in the kidney do not essentially differ in age, daily diuresis, average hematocrit values and kidney size from the patients having solitary cysts or from those without any cyst. On the other side, those patients take significantly more time to be treated by chronic hemodialysis. Following the results obtained in this study, we conclude that cystic transformation of the kidneys in chronic hemodialysis patients is the benign disease. The findings pointing out at solitary cysts among this group of patients may also present a stage in the development of acquired multicystic kidney transformation. Only partial reliability of diagnosing the disease by ultrasonography and benignity suggest that regular ultrasonographic controls of those patients are not necessary. PMID- 2097471 TI - [Strumal carcinoid tumor of the ovary--histologic and electron microscopy characteristics of the tumor]. AB - Strumal carcinoid tumor is a very rare primary tumor of the ovary in which carcinoid is admixed with tissue resembling thyroid follicles. We report a 44 year-old women with benign strumal carcinoid tumor of the ovary and without any clinical symptoms. Histochemical and electron microscopical examinations of the tumor showed intracytoplasmic dense core secretory granules, indicating that this neoplasm is a pure carcinoid tumor with acinar differentiation resembling thyroid tissue. PMID- 2097470 TI - [Tuberous sclerosis with epilepsy in monozygotic twins--a new mutation]. AB - A 4.5-year-old female twins with tuberous sclerosis are presented. The main clinical manifestations were partial epileptic seizures with complex symptomatology. Repeated EEGs were normal in both twins, while CT scans revealed periventricular calcifications of the brain. The twins were assumed to be monozygotic, what was confirmed with laboratory findings: HLA, identical erythrocyte, enzymatic and protein antigens were found. Skin transplant exchange was not performed. Since both parents do not have any signs of tuberous sclerosis, in this case the disease which is otherwise inherited as an autosomal dominant trait most probably was due to a new mutation which had occurred. PMID- 2097472 TI - [Syncope caused by iatrogenic hypercalcemia]. AB - A course of the disease of a 68-year-old female who had been taking medigoxin, furosemide, verapamil and an unknown amount of spironolactone and potassium salt due to congestive heart failure is presented. She was admitted to emergency department of the University Hospital Rebro after an episode of syncopal attack because of arrhythmia due to hyperkalemia (8.9 nmol/L). She has had a fast idioventricular rhythm, followed by atrial tachycardia after that and with fast ventricular rhythm, S-T segment depression and a tall and peaked T-wave. In the following electrocardiograms left anterior hemiblock appeared, a tall R-wave of the anterolateral location, supraventricular and ventricular premature beats and atrioventricular block of the first degree. The patient had signs of non-oliguric form of acute renal failure at the admission which was a partly explanation for the development of hyperkalemia, together with the use of spironolactone and potassium salt. After the treatment she had normal serum creatinine values. She suffered from combined mitral valve disease: stenosis with a predominant regurgitation of the II/III degree. She was discharged from the hospital in a compensated state with normal serum potassium values. PMID- 2097474 TI - [Primary neuroendocrine carcinoma of the skin (Merkel cell tumor)]. AB - Three cases of neuroendocrine carcinoma of the skin studied by light and electron microscopy and by immunohistochemical methods, are presented. It is generally accepted that these tumors originate from Merkel's cells. Some consider that they belong to the group of APUD-omas. Positive findings of epithelial (EMA, CAM 5.2) and neuroedocrine marker (NSE) in these three cases support the hypothesis of neuroendocrine differentiation in a neoplasm of epithelial origin. PMID- 2097473 TI - [Adenocarcinoma of the colon in a 14-year-old boy]. AB - We report the case of a 14-year-old boy with adenocarcinoma of the colon. The diagnosis was established 3 months following the initial symptoms. The tumor was located in the region of the descending colon and was of Dukes B stage. The patient underwent left hemicoloctomy followed by chemotherapy and irradiation. In the follow-up period of two years the patient has been well. It is concluded that early diagnosis, adequate monitoring of patients by the determination of carcinoembryonic antigen and regular follow-up visits could lead to better prognosis. PMID- 2097475 TI - [The fragile X (Martin-Bell) syndrome]. AB - Fra (X) or Martin-Bell syndrome is the most common X-linked mental retardation with an incidence of 1/1000-2000 newborns. Chromatid break, double chromatid break or total loss of distal part of X chromosome (which occurs most often inside the C positive band q 27.3) is demonstrated in most male hemizygotes as mental retardation and specific phenotypic features. Fra (X) syndrome is proved in the cultured lymphocytes or fibroblasts with special cytogenetic methods. The prenatal diagnosis is possible by examining of amniotic fluid or the lymphocytes from the umbilical cord. We report two families with fra (X) syndrome. In the first one, 6 year- and 9-month-old boy with mental retardation and characteristic phenotypic features has been recognized as the carrier of fra (X) syndrome and after that his 4-year-old brother with similar symptoms. In the second family, there is a severe mentally retarded 3-year-old boy with fra (X) syndrome who besides typical phenotipic changes also exhibits symptoms of autism. The percentage of the cells with fra (X) chromosome in our patients (30%, 28%, 18%) is not correlated with the degree of their mental retardation. The mothers of our patients are the heterozygous carriers of the syndrome (3% and 1.5% fra (X) chromosome). PMID- 2097476 TI - [Inborn metabolic errors of urea cycle synthesis. Present possibilities of treatment]. AB - The case history of an infant with congenital hyperammonaemia due to inherited ornithine-transcarbamylase deficiency is presented together with some basic data on his family. The metabolic cycle of urea synthesis is delineated with its enzymes and the possible inherited defects. The differential diagnosis of hyperammonaemia in the newborn infant is given. The successful contemporary method of therapy of urea cycle disorders is presented. PMID- 2097477 TI - [Immunology of cardiovascular diseases in children]. AB - Cardiovascular diseases in children are most usually caused by the disturbances in the immune system. The disease very often occurs after infections with a secondary immune response to the cardiovascular system; lately there are more frequently secondary responses after surgical treatment on the heart. Passive transfer of maternal antibodies through the placenta results particularly in congenital complete heart block in newborns and infants. Rheumatic heart disease is the most usual manifestation of humoral and cell-mediated reactivity in patients. Due to cardiotoxicity of eosinophils, endomyocardial diseases with eosinophilia are developed. There is a problem of arteritis of the coronary arteries as part of some allergic diseases, especially of Kawasaki disease. Immunologically mediated diseases of the cardiovascular system in children need further studies. PMID- 2097478 TI - [Incorrect use of the term "cuspis"]. PMID- 2097479 TI - [Hospital treatment of child-tourists at the Pula Medical Center 1983-1988]. AB - During the 6-year period, 687 children-tourists, aged up to 12 years, were treated at the departments of the Medical Center of Pula; on average 114.5 (standard deviation +/- 17.79) children per year. There were 449 (65.4%) patients from different parts of Yugoslavia and 238 (24.6%) from abroad. Two hundred and fifty-four (37.9%) patients were treated at the Department of Paediatrics 231 (33.7%) at the Department of Surgery, 168 (24.4%) at the Department of Infectious Diseases, then 30 (4.4%) at the Department of Ear, Nose and Throat, 3 female patients (0.4%) at the Department of Gynecology and only one boy was treated at the Department of Ophthalmology. There were 22 (3.2%) newborns, 48 (7%) infants, 143 (20.8%) were one to three years old, then 130 (18.9%) were 4 to six years old and 344 (50.1%) older than 7 years. During the 6-year period, children-tourists accounted for 5.1% of the hospitalized children. 81.3% of the patients were treated during June, July and August, the peak being in July (39%). The most frequent diseases were from the group "infectious and parasitic diseases" (188 patients = 27.4%) and among them "diarrheal syndrome" in 82% of patients, then the group "injuries and poisons" (140 patients 20.4%) among which there were 57 (40.4%) superficial injuries, contusions and open wounds, then in 33 (23.5%) patients different fractures; in this group 10% of children were poisoned mostly by drugs (sedatives and tranquilizers) used by their parents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097480 TI - Flumazenil as an antagonist for midazolam anesthesia in outpatient surgery. AB - Rapid recovery is an essential component in the anesthesia of OPD surgery. In this study midazolam, the short-duration benzodiazepine, was used as an intravenous anesthetic in OPD surgery. At the end of the operation flumazenil, the specific antagonist of benzodiazepines, was given to reverse the effect of midazolam. Recovery of these patients was compared with those in the control group who received saline instead of flumazenil. In a randomized, placebo controlled clinical study the antagonistic effect of flumazenil on midazolam was investigated in fifty ASA class I-II gynecologic outpatients subjected to D & C procedure under anesthesia induced with midazolam (0.3 mg/kg). They were divided into group A (flumazenil group) and group B (placebo group) with 25 patients in each. At the end of operation patients in group A were given 0.2 mg flumazenil intravenously to antagonize the residual effect of midazolam while patients in group B were given 2 ml normal saline intravenously as control. Our results showed that patients in group A exhibited a rapid and steady return of consciousness scaled by alertness, orientation of time and place and activity collaboration at 5, 30 and 60 min intervals following administration of flumazenil (p less than 0.005). There were no significant changes found in the hemodynamic or respiratory aspect between groups (p greater than 0.05). All the patients tolerated midazolam and flumazenil well. It is concluded that the use of flumazenil to antagonize the residual effect of midazolam is safe and effective as far as outpatient procedure is concerned. PMID- 2097481 TI - [Renal effect of isoflurane]. AB - Isoflurane is a pentafluorinated methyl ether and can be metabolized to inorganic fluoride in man. Nephrotoxicity may be developed after it's administration. The present study was carried out to evaluate the effects of isoflurane on renal hemodynamic and excretory function in 15 patients. The systolic, diastolic and mean arterial pressure and renal function were measured before, during and after induction of anesthesia by isoflurane. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were estimated by the clearances of paraaminohippuric acid and inulin, respectively. The results showed that a slight reduction in systolic pressure but no significant change in diastolic and mean blood pressures were found during anesthesia. There were 30% and 50% reductions in RPF and GFR, respectively. The filtration fraction increased significantly. Simultaneous decreases in urine flow, absolute and fractional excretions of sodium, absolute excretion of potassium, osmolar clearance and free water reabsorption rate were observed during isoflurane anesthesia. However, the blood pressure and renal function returned to pre-anesthesia levels 30-60 minutes after termination of anesthesia. These data suggest that isoflurane induces renal depressive effect which is reversible and temporary. PMID- 2097482 TI - Subpleural block in patients with multiple rib fractures. AB - Multiple rib fractures result in agonizing pain as well as impaired pulmonary functions. Mechanical ventilations are frequently indicated for those with poor respiratory reserves. Regional anesthesia has been advocated for easing pain and discomfort. We evaluate the efficacy of subpleural block in the treatment of multiple rib fractures. Ten patients who sustained multiple rib fractures were observed on the arrival of emergent service. One sustained flailed chest with respiratory distress which necessitated mechanical ventilation in intensive care unit. Subpleural block with 20 ml 0.5% bupivacaine was done to each patient. The location of catheter was identified by the injection of contrast medium. Serial visual analogue pain scale, arterial blood gas, and pulmonary function test were taken before and after subpleural block. Pulmonary function test significantly improved after subpleural block. Pain relief was immediate and desirable. The case in ICU weaned from ventilator 3 days later. There were no major complications after subpleural block. Inadvertent epidural spread and recurrent laryngeal nerve blocks were detected both clinically and radiologically without sequela noted. Subpleural block is effective both in pain relief and in improving pulmonary functions. Image intensifier is essential to subpleural block in order to prevent the misplacement of catheter. We recommend subpleural block to be an alternative approach of regional anesthesia in patients with multiple rib fractures. PMID- 2097483 TI - Assessment of atracurium during anesthesia and surgery. AB - Atracurium is a competitive neuromuscular blocking agent which goes through Hofmann elimination. It does not accumulate even after several bolus doses or infusion lasting several hours. The purpose of this study was to evaluate the effectiveness of atracurium on bolus injection for intubation and continuous infusion for subsequent surgery with the manufacturer's suggested dose. Forty-six patients (23-78 yr, ASA I-IV) undergoing laparotomy were included in the study. The patients were induced with Thropental and fentanyl, then a bolus of atracurium (0.5 mg/kg) was given and intubation done 90 sec later. Anesthesia was maintained with nitrous oxide, oxygen and isoflurane. Twenty minutes later atracurium 0.3 mg/kg/hr was infused continuously. The infusion continued until skin closure or an estimated 20-30 min before the end of the operation. Quality of muscle relaxation for intubation and surgery was evaluated by the surgeons and the anesthesiologists. Train-of-four (TOF) count was also recorded in the beginning and at the end of infusion. After extubation, residual curarization was evaluated clinically and with the TOF count method in the recovery room. Intubation quality was rated fair to poor in 67% of cases. Muscle relaxation assessed by the surgeons as excellent to good amounted to 96% of cases. All patients were extubated within 30 min after completion of surgery except for five patients who had poor postoperative conditions because of underlying diseases. No patient showed residual curarization or complication in the recovery room. With doses suggested by the manufacturer, our study indicated that intubation was not satisfactory while continuous infusion for muscle relaxation during surgery was acceptable. PMID- 2097484 TI - The effect of volume of epidural morphine on postoperative analgesia in patients undergoing cesarean section. AB - Ninety paturients undergoing elective cesarean section were included in this randomized study to compare the influence of the injected volume of epidural morphine (EM) on postoperative analgesia. Three similar groups of patients (n = 30 each) received 2 mg EM in 2 ml, 10 ml, and 20 ml saline respectively one hour after the last dose of 2% lidocaine. Pain scores (0-10) at rest (including uterine contraction pain) at the 2nd, 4th, 8th, 12th, 18th, and 24th h were compared among the three groups. There were no statistically significant differences of pain score among the three groups although lower pain score was present in the 20 ml group since the 8th h and thereafter. Regarding the number of patients who requested additional meperidine for pain relief 3 in 2 ml group, 2 in 10 ml group and 1 in 20 ml group respectively. The result may suggest that the influence of the injected volume of EM on postcesarean analgesia is not obvious. PMID- 2097485 TI - The evaluation of subarachnoid administration of fentanyl for surgery and postoperative analgesia in patients undergoing cesarean section. AB - The use of spinal opioids for postoperative analgesia has gained popularity in recent years. In this study, subarachnoid fentanyl 20 micrograms was evaluated to determine its efficacy for postoperative analgesia, its possible side effects and its effects on the newborn. Sixty ASA class I or II at-term parturients undergoing elective cesarean section were randomly divided into two groups. In one group fentanyl 20 micrograms (0.4 ml) with 0.5% heavy marcaine 2.0 ml was given intrathecally and in the other group only 0.5% heavy marcaine 2.0 ml with CSF 0.4 ml was given intrathecally. The average time for patients in the fentanyl group to demand the first dose of narcotic for pain was 6.8 +/- 3.2 h and in the control group it was 3.9 +/- 1.1 h. The incidences of postoperative nausea and vomiting were higher in the fentanyl group than in the control group. Pruritus was only found in the fentanyl group and amounted to 50%. Early or late respiratory depression was not found in the fentanyl group. During operation, all patients were wakeful and alert. Neonatal condition as determined by 1-min and 5 min Apgar score was satisfactory and showed no significant difference in both groups. Examination on neurobehavior and reflexes done at the baby room showed no abnormality in both groups. PMID- 2097486 TI - [Does flumazenil antagonize the anesthetic effect of ketamine, etomidate or thiopental?]. AB - The effect of flumazenil, a benzodiazepine antagonist, was assessed in a random, double-blind clinical study in which each of the four groups of surgical outpatients comprising 20 in each was given either ketamine 100 mg (K), etomidate 20 mg (E), thiopental 300 mg (T) or flunitrazepam 4 mg (F) for induction of anesthesia. On emergence, patients in each group were randomly given 2cc of either 2 coded solutions, one of which contained 0.2 mg flumazenil and the other of which was normal saline. Following injection of coded solution, all patients were assessed at 0, 5, 15, 30, 60 and 120 min for wakefulness. All 10 patients of group F who received flumazenil were alert and able to recall at 5 min, whereas in group T this was noted from 15 to 30 min. Patients of group E and K responded alike in a manner as of those who received normal saline placebo with onset of wakefulness at 30 and 60 min respectively. These results confirm that flumazenil antagonizes flunitrazepam (within 5 min) and also indicate that the antagonizing effect occurs 30 min following injection for thiopental, suggestive of some cross reactivity between these two drugs. PMID- 2097488 TI - The use of ketanserin for postoperative hypertension after abdominal surgery. AB - Eighteen adult patients who developed hypertension (systolic blood pressure greater than 160 mmHg, diastolic blood pressure greater than 90 mmHg or both) at the early recovery period after major abdominal surgery were included in the study. Following intravenous injection of 10 mg ketanserin, eleven out of eighteen patients (61%) had their systolic or diastolic blood pressure fell below the target mark (160 mmHg and 90 mmHg), and the decrease was statistically significant (p less than 0.01 up to 120 min). There was no statistically significant change in heart rate. Four patients (22%) responded to 20 mg of ketanserin. Three patients (17%) did not have significant decrease of the blood pressure after 20 mg of ketanserin and they received other antihypertensives instead. No severe hypotensive episode was noted. We concluded that ketanserin is a moderate, rapid-onset and safe antihypertensive agent in treating postoperative hypertension following major abdominal surgery. PMID- 2097487 TI - [The effect of epidural anesthesia on tourniquet pain: a comparison of 2% lidocaine and 0.5% bupivacaine]. AB - The incidence of tourniquet pain was evaluated in two groups of patients with 20 each undergoing orthopedic surgery of the lower extremities during epidural anesthesia using plain solution of either 2% lidocaine or 0.5% bupivacaine. The drugs were administered in a randomized fashion. Measurement of the levels of sensory loss to pinprick and incidence of tourniquet pain were made by blind trust. The maximum analgesia level, time between 1st injection and onset of pain, time between tourniquet inflation and onset of pain were recorded similarly in both groups of patients. The incidence of tourniquet pain was significantly greater in patients given 2% lidocaine (40%) than in patients given 0.5% bupivacaine (10%). The incidence of pain was not related to the time of tourniquet inflation, because patients in the bupivacaine group had a significant longer duration of tourniquet inflation than did patients in the lidocaine group. The incidence of pain was also not related to tachyphylaxis, because 7 of 8 patients who complained tourniquet pain in lidocaine group received less than 3 injections for maintenance of analgesia when tourniquet pain started. In summary, it is apparent that tourniquet pain occurs less frequently when bupivacaine is employed for epidural anesthesia as compared to lidocaine. PMID- 2097489 TI - Anesthesia for cardiac transplantation. PMID- 2097490 TI - Clinical application of infrared thermography in diagnosis and therapeutic assessment of vascular ischemic pain. AB - Temperature is a very important and useful manifestation of various disease entities. The importance of body temperature as an indicator of disease has been known for centuries but in recent years attention has also been paid to how to conveniently and effectively make use of skin temperature as a diagnostic tool. Skin temperature can be measured with thermocouples, electronic thermistor thermometers, electronic integrators, liquid crystal thermography, and infrared thermography. The temperature of extremities is largely dependent on the blood flow through peripheral vessels, and in the study of vascular diseases thermography has been, therefore, found to be useful. Blood flow can be assessed by many methods including washout techniques or laser Doppler flowmetry. Of these, infrared thermography has the advantages of being noninvasive, remote from the patient when in use, and capable of producing multiple recordings at short time intervals. Here we present a case of vascular ischemic pain which was diagnosed and therapeutically assessed by thermography. PMID- 2097491 TI - [Burns caused by electrocautery during surgery]. AB - A 19-year-old male suffering from crushed injury on the neck and anterior upper chest with suspected laceration of the trachea underwent emergent operation for surgical restoration of the trachea. First and second degrees of electric burns over the neck and upper back regions(4%) were accidentally caused by electrocautery during surgery. Short circuit due to over-wetting of the sheet and EKG leads may be responsible for this avoidable accident. PMID- 2097492 TI - Characterization of outer membrane proteins from Actinobacillus actinomycetemcomitans. AB - Outer membranes were prepared from whole cells of various strains of Actinobacillus actinomycetemcomitans and analysed by SDS-polyacrylamide gel (12.5%) electrophoresis (SDS-PAGE). In all strains four common major outer membrane proteins (OMPs) with molecular masses of 30, 34, 36 and 39 kDa could be distinguished. Heating the OMP preparation of strain Y4 at 60, 70, 90 and 100 degrees C produced a band of 30 kDa, which gradually lost its intensity from 70 degrees C onwards concomitantly with the development of two new protein bands of 34 and 36 kDa. Furthermore, the 36 kDa OMP appeared susceptible to proteolysis by trypsin; degraded products apparently produced a new electrophoretic band of 27 kDa. Y4-derived OMP fractions were solubilized with a Triton-SDS mixture to investigate the presence of peptidoglycan-associated proteins. The 39 kDa OMP was found to be peptidoglycan-associated. PMID- 2097493 TI - Vaccination of chickens with a Salmonella enteritidis aroA live oral Salmonella vaccine. AB - A mouse-virulent strain of Salmonella enteritidis, Se795 (LD50 less than 10 organisms for mice), was non-virulent for 12-day-old chickens given 10(6) cfu intravenously; the organisms were cleared from liver and spleen by day 14 as measured by direct plating and by day 21 by enrichment. An Se795aroA mutant, CU58, was also cleared from liver and spleen by day 14 after intravenous inoculation of 10(7) cfu. Day-old chicks vaccinated orally with either one dose of 10(9) CU58 at 1 day of age, 10(7) at 1 and 14 days, or 10(5) at 1 and 7 days followed by 10(9) at 14 and 21 days of age, were challenged orally with a nalidixic acid resistant variant of the virulent phage type 4 S. enteritidis strain 109. All vaccinated groups showed a reduction in faecal shedding of the challenge. Chickens given four doses of CU58 showed a significant reduction of cfu in liver, spleen and faeces following intravenous challenge with virulent strain 109. Intramuscular vaccination with 10(9) cfu of Aro strain CU58 at 1 day of age gave no protection against oral challenge with virulent strain 109. Serum antibody production to LPS (ELISA) was minimal in all vaccinated birds. The results indicate that oral vaccination with Aro- S. enteritidis can confer protection to day old chicks against virulent S. enteritidis. PMID- 2097494 TI - The effect of Streptococcus pneumoniae pneumolysin on human respiratory epithelium in vitro. AB - Streptococcus pneumoniae culture filtrates and pneumolysin both slow human ciliary beating and damage respiratory epithelium in vitro. A polyclonal pneumolysin antibody bound to sepharose beads removed pneumolysin from culture filtrates and showed that pneumolysin alone was responsible for the effects on epithelium. In a 48-h organ culture pneumolysin caused ciliary slowing and epithelial disruption in a dose-dependent manner down to 5 ng/ml. Comparison of the ciliary slowing activity and pneumolysin concentration in filtrates in a continuous broth culture showed a maximal effect at 16 h (pneumolysin 7.5 micrograms/ml). Later the activity decreased while the pneumolysin concentration increased (8.8 micrograms/ml). This loss of activity was prevented by neutralisation of the acid pH of the culture medium. Eight different culture filtrates produced significant (P less than 0.05) ciliary slowing which correlated (r = 0.95) with simultaneously measured haemolytic (pneumolysin) activity. Substitution of tryptophan (position 433) by phenylalanine reduced the haemolytic and ciliary slowing activity of pneumolysin, but did not affect its ability to activate complement. There was no correlation between the ciliary slowing produced by the culture filtrate and that produced by the autolysate of a particular strain, nor between ciliary slowing and the extent of autolysis or the serotype of the strain. PMID- 2097495 TI - Cyclophosphamide and prednisolone exacerbate the severity of intestinal paratuberculosis in Mycobacterium paratuberculosis monoassociated mice. AB - In this study we examined the effects of continuous oral administration of the immunosuppressive agents cyclophosphamide and prednisolone on the susceptibility of gnotobiotic nu/+ BALB/c mice to intestinal paratuberculosis. Treatment with either cyclophosphamide or prednisolone led to fecal shedding of Mycobacterium paratuberculosis, and increased the numbers of M. paratuberculosis recovered from the intestinal tract and liver, to levels similar to those recovered from untreated nu/nu mice. Numerous acid-fast bacilli and granulomas were observed within the intestinal tracts and livers of cyclophosphamide and prednisolone treated nu/+ and untreated nu/nu mice. In contrast, untreated control nu/+ mice infrequently shed small numbers of bacilli, harbored low numbers of M. paratuberculosis in their intestinal tracts, and did not have visible granulomas and acid fast bacilli in their tissues. Spleen cells from cyclophosphamide and prednisolone treated nu/+ mice, and from untreated nu/nu mice, had a reduced ability to proliferate in vitro in response to mitogen and antigens. These observations are consistent with previous evidence that cellular immunity restricts the development of intestinal paratuberculosis. PMID- 2097496 TI - Adherence of Helicobacter pylori cells and their surface components to HeLa cell membranes. AB - Four Helicobacter pylori strains were used to develop in vitro methods to assess adherence to HeLa cells. Using direct detection by microscopy, adhesion scores increased with the initial bacteria-to-cell ratio. The urease method assessed H. pylori bound to HeLa cells by their urease activity. The percentage of the original inoculum adhering to HeLa cells remained constant for initial ratios from 10(2) to 10(5) bacteria per cell. An ELISA using anti-H. pylori serum assessed whole bacteria or components bound to HeLa cell fractions. By all three methods, the four H. pylori strains were adherent to HeLa cells or membranes whereas Campylobacter fetus and Providencia control strains were not. The adherence of H. pylori whole cells decreased following extraction with saline, water, or glycine buffer and most of the superficial adhering material (SAM) was present in the saline or water extracts. SAM bound better to HeLa membranes than to calf fetuin or bovine serum albumin (BSA); binding was inhibited by preincubation of SAM with HeLa membranes but not with fetuin or BSA or by pretreatment of HeLa membranes with neuraminidase. These data indicate that SAM has a specific receptor on the HeLa cell membranes. By gel exclusion chromatography of bacterial extracts, the most adherent components were found in the fractions which also contained the highest urease activity; these fractions included urease subunit antigens. We conclude that adherence of H. pylori can be assessed by microtiter assays and involves bacterial surface material which co purifies with urease and is different from the N-acetyl-neuraminyl-lactose binding hemagglutinin. PMID- 2097497 TI - [The isolation and characteristics of variant plague microbes not producing the capsular antigen]. AB - Fifteen stable variants of Yersinia pestis strains exhibiting different degrees of virulence for white mice and guinea pigs were obtained. Multiple passages of the organisms at 37 degrees C in a fluid nutrient medium containing antiplague agglutinating serum were found to be the most efficient method for obtaining noncapsular forms of the plague agent. Acquisition of the Fra(-) phenotype both by wild and laboratory strains was not associated with a loss of the high molecular plasmid by cells but was probably a result of mutational alterations in the plasmid genes. PMID- 2097498 TI - [The choice of the optimal aeration conditions for the stab cultivation of Bacillus thuringiensis H14 266/2-1]. AB - Optimal conditions of aeration with depth regime of cultivation of Bacillus thuringiensis H14 266/2-1, their effect on the output of biomass, endotoxin and activity of bacteria have been studied. The aeration conditions are optimized using the mathematical method of experiment planning. It is established that the air supply favours an increase of the bacillary biomass and insecticide activity for the whole cultivation period. In the first day of fermentation it is inexpedient to increase to rate of the medium agitation. To obtain a high titre of cells of the studied bacilli and to retain their activity a specific air consumption is recommended amounting to 0.5 1/1/min for the first 12h with an increase to 1.01/1/min in the following hours of fermentation, the constant rate of the medium agitation being 500 rev/min. PMID- 2097499 TI - [The antimicrobial activity of desoxon-5 in the disinfection of plastics used in dental practice]. AB - The disinfecting effect to the new preparation--desoxon-5 when decontaminating plastics, used in stomatology, plastic removable [correction of demountable] dentures and orthodontic, apparatus, infected by test microbes has been studied. One of the results of the work is the determination of desoxon-5 concentrations, causing the death of test microbes on the surface of plastic objects. It is proposed to include the use of desoxon-5 as an active decontaminating preparation into the number of means on looking after removable [correction of demountable] plastic dentures. PMID- 2097501 TI - [Suppression of the "fast" IPSP when superimposed on the "slow" IPSP as a possible cause of priming in the mouse hippocampus]. AB - Extra- and intracellular responses of the mouse hippocampus were recorded at CA1 region after stimulation of two independent inputs from the Schaffer collateral/commissural fibres: conditioning or priming input (C1) and testing or primed one (C2). Duration and amplitude of primed field potentials (FP) and excitatory postsynaptic potentials (EPSP) as well as amplitudes of early (IPSPa) and late (IPSPb) components of inhibitory postsynaptic potentials (IPSP) were measured with variation of C1-C2 intervals from 0 to 1 s. An increase in the FP duration as well as EPSP duration and amplitude and suppression of the IPSP amplitude occurred after conditioning with intervals of 50-500 ms, maximal effect was at 200 ms ("priming" effect). These changes correlated with the amplitude of priming IPSPb. The most prominent effect was observed in cells with hyperpolarizing IPSPa. It is assumed that primed FP and EPSP increase due to suppression of the primed IPSPa, when it is superimposed on the priming IPSPb. PMID- 2097500 TI - [A method for determining phospholipases in microorganisms]. AB - A method is suggested for the determination of bacteria phospholipases in dense nutrient medium. The medium contains the egg-yolk solution, buffer pH 9.2, meat extract, calcium chloride and toluidine blue. The enzyme activity is estimated by the diameter value of the medium clarification zone around the bacterial mass inoculation by injection into an agar plate. It is possible to study 6-8 strains on one Petri dish. This method is a simple one and thus it can be used in the bacteriological practice when determining phospholipases of bacteria, especially in strains of those species where this enzyme is a pathogenicity factor. PMID- 2097502 TI - [The connections of the parietal cortex with the lateral suprasylvian gyrus (the Clare-Bishop field) and the auditory cortex in the cat]. AB - It has been shown that a parietal projection to the Clare--Bishop area is moderate and organized in a topographic manner. Associative fibres of area 5 terminate in the anterior part of the Clare--Bishop area, which corresponds to the intermediate and anterior part of the posterior suprasylvian sulcus belt. Area 7 projects to the posterior part of the intermediate and posterior suprasylvian sulcus belt. Area 5 and 7 send a few fibres to the auditory cortex. Associative fibres of area 5 terminate in the middle ectosylvian and sylvian gyri: areas 22, 50. Area 7 is connected only with the superior extremity of the middle ectosylvian gyrus or of areas 22, 50. PMID- 2097503 TI - [Plastic synaptic reorganization in the sensorimotor cortex of adult cats after destruction of the contralateral nucleus intermedius of the cerebellum]. AB - Using the intracellular microelectrode technique the reactions were investigated in corticospinal neurons (CSN) after stimulation of contralateral (cIP) and ipsilateral interpositus nucleus of cerebellum as well as ventrolateral nucleus of thalamus. Experiments were made on adult intact cats and the same preliminary lesion of cIP nucleus (exposition from 1 to 6 months). Acceleration of the monosynaptic thalamo-cortical EPSPs time to peak in slow CSN was revealed in operated animals. It indicated that there was remote terminal dendrosomatic sprouting and formation of new synapses on proximal segments of SD-membrane of CSN. This made it possible to suppose that there was formed ipsilateral interposito-thalamocortical way which duplicated the same contralateral in intact animals. The contralateral cortico-interposital collaterals in intact and the analogic ipsilateral sprouting in operated animals have been shown. PMID- 2097504 TI - [A cytophotometric study of the monoamines and energy metabolism enzymes in the neurons of the paravertebral ganglia under cold-induced and emotional stress]. AB - The content of monoamines and energy exchange enzymes in neurons of the stellate ganglion (SG) and Th6-Th10 thoracic sympathetic trunk ganglia (TSTG) was studied histochemically using a computer analysis. Intensification of the monoamine fluorescence and energy exchange enzyme activity in SG neurons was found both during cold and emotional stress. Similar changes in TSTG were observed only during hypothermia. A selective activation of neurons of the paravertebral ganglia under different stresses is suggested. PMID- 2097505 TI - [Taurine-activated currents in isolated neurons of the rat cerebellum]. AB - Taurine-activated currents in isolated neurons of the rat cerebellum were studied by voltage and "concentration" clamp methods. They were transmitted by potassium and chloride ions. The dose-response curve with the dissociation constant 2 x 10( 3) mol/l was obtained. The cross-desensitization between taurine and GABA, but not between taurine and glycine was shown. These currents were also blocked by bicucullin and strychnine, but in a different manner. PMID- 2097506 TI - [The neuronal mechanisms of the defensive reaction to stimulation of the cutaneous nerve in the freshwater snail]. AB - The whole body withdrawal reaction of freshwater snail Planorbarius corneus consists of two phases. In the first phase the shell is rapidly moved down to cover the head, in the second one the body is slowly retracted into the shell. The columellar muscle is involved in this behaviour. Motoneurons of the columellar muscle are identified in the cerebral, parietal and pedal ganglia. In the preparation of the central nervous system connected with the columellar muscle it is demonstrated that stimulation of the lip nerve evoked a biphasic motoneuron excitation responsible for two phases of the muscle contraction. A similar biphasic excitation of the motoneurons could arise spontaneously. This implies that the whole body withdrawal reaction is, at least partly, a fixed act generated by a central mechanism (a central program) which is triggered by a sensory stimulus. The central mechanism of the withdrawal reaction could be also activated by a depolarization of some columellar motoneurons. This suggests that the central mechanism received a feedback from the motoneurons. PMID- 2097507 TI - [The neuronal mechanisms of the escape reaction to stimulation of the statocyst receptors in the freshwater snail]. AB - Tilts of the freshwater snail Planorbarius corneus, resulting in statocyst receptor stimulation, induced the defensive reaction including pulling down of the shell, shortening of the foot, inhibition of locomotion and feeding. The preparation of the central nervous system has demonstrated that many inter- and motoneurons from different ganglia were involved in this reaction. Usually the reaction was of "all or none" manner. The repeated reaction of the second tilt could be evoked not earlier than 10-20 s after the previous one. It is concluded that the defensive reaction to statocyst receptor stimulation is a "fixed act" determined by a special central mechanism (a central program). The reactions to stimulation of statocyst receptors and skin nerve are proved to be generated by the same mechanism. PMID- 2097508 TI - [A dynamic study of the impulse processes in human cerebral neurons by using the principal-component method]. AB - Evoked activity (EA) of single neurons to verbal (or sensory) stimuli was recorded by microelectrodes in the nucleus reticularis and some other thalamic nuclei of the human brain during stereotaxic operations. An approach is considered which results from the assumptions of the cumulativeness and variability of the EA pattern and is based on the principal component analysis and peristimulus covariation matrices. Application of these methods for estimating unitary responses showed their efficiency for the quantitative analysis of the dynamic structure and interneuronal relations within the EA patterns during the performance of voluntary motor acts. PMID- 2097509 TI - [The possible role of changes in calcium conduction in the early enhancement of spinal reflex responses after dissection of the sciatic nerve]. AB - Effects of imidazol, 4-aminopyridin and verapamil on evoked monosynaptic responses 5-7 days after cutting of the sciatic nerve have been studied in white rats. Imidazol induced no changes for certain 4-aminopyridin increased and verapamil decreased amplitude of responses on the side of cutting nerve. PMID- 2097511 TI - Characteristics of Cl(-)-dependent L-[35S]cysteic acid transport into rat brain synaptic membrane vesicles. AB - Uptake of L-[35S]cysteic acid (L-CA) in rat synaptic membrane vesicles was investigated. Preincubation with either 10 mM L-glutamic acid (L-Glu), 25 mM L CA, 10 mM DL-homocysteic acid, or 25 mM DL-2-amino-4-phosphonobutyrate on membrane vesicles enhanced L-[35S]CA and L-[3H]Glu uptake. Na+ (5 mM) and omission of Cl- from the assay medium decreased L-[35S]CA uptake into both 10 mM L-Glu-loaded and non-loaded membrane vesicles. The anion transport blockers, 4 acetamide-4'-isothiocyano-2,2'-disulfonic acid stilbene (SITS) and 4,4' diisothiocyano-2,2'-disulfonic acid stilbene (DIDS), inhibited L-[35S]CA uptake in a dose-dependent manner. The maximal uptake rate for L-[35S]CA was decreased by 50 microM SITS, while the apparent Km value of L-CA was not changed. SITS increased the EC50 value of Cl- for L-[35S]CA uptake from 5 mM to 10 mM with reduction of the maximal effect. These results suggested that L-[35S]CA uptake into synaptic membrane vesicles was mediated by a SITS-sensitive hetero-exchange transport with non-labeled substrates. PMID- 2097510 TI - [The organizational characteristics of the motor representation of the vibrissae in the frontal cortex of the rat]. AB - Bilateral mapping of the frontal cortex of rat has been performed. The internal topographic organization of motor zones of the vibrissae was revealed with the low-threshold microstimulation. The comparison of the right and left hemispheres demonstrated some asymmetry in the vibrissae motor representation, its territory in the right hemisphere being larger than that in the left one. PMID- 2097512 TI - Patterns of endogenous gangliosides and metabolic processing of exogenous gangliosides in cerebellar granule cells during differentiation in culture. AB - The qualitative and quantitative pattern of endogenous gangliosides and the routes of metabolic processing of exogenous GM1, 3H labeled in the sphingosine moiety (Sph-3H GM1) were studied in cerebellar granule cells during differentiation in vitro. During the first 7-8 days in culture the ganglioside content markedly increased, and the qualitative pattern showed, in percentage terms, a drastic decrease of GD3 and a marked increase of GD2, O-Ac-GT1b, O-Ac GQ1b and GQ1b. After pulse with (Sph-3H) GM1, at all the investigated days in culture, different radiolabelled lipids were formed indicating that taken up exogenous GM1 was degraded and that its catabolic fragments, and partly GM1 itself, were used for biosynthetic purposes; moreover radioactive water was measured in the culture medium during chase indicating that labelled sphingosine underwent also degradation. The uptake of exogenous GM1 and the extent of its metabolic processing per cell unit increased during differentiation: a) GM2 was the major metabolic product and was relatively more abundant at 2 than 7 days in culture; b) the percentage of metabolites of biosynthetic origin over total metabolites increased during differentiation, especially at the short pulse times; c) among the metabolites of anabolic origin sphingomyelin equalled gangliosides at 2 days, whereas it was largely overcome by gangliosides at 7 days in culture; d) at 4 and 7 days in culture a radioactive substance, not yet identified, was present, whereas no trace of it was found at 2 days. In conclusion, cerebellar granule cells in culture feature a different pattern of endogenous gangliosides and display different ability to metabolically process exogenous GM1 ganglioside in the undifferentiated and fully differentiated stage. PMID- 2097514 TI - Cu(II) and Zn(II) ions alter the dynamics and distribution of Mn(II) in cultured chick glial cells. AB - Previous studies revealed that Mn(II) is accumulated in cultured glial cells to concentrations far above those present in whole brain or in culture medium. The data indicated that Mn(II) moves across the plasma membrane into the cytoplasm by facilitated diffusion or counter-ion transport with Ca(II), then into mitochondria by active transport. The fact that 1-10 microM Mn(II) ions activate brain glutamine synthetase makes important the regulation of Mn(II) transport in the CNS. Since Cu(II) and Zn(II) caused significant changes in the accumulation of Mn(II) by glia, the mechanisms by which these ions alter the uptake and efflux of Mn(II) ions has been investigated systematically under chemically defined conditions. The kinetics of [54MN]-Mn(II) uptake and efflux were determined and compared under four different sets of conditions: no adducts, Cu(II) or Zn(II) added externally, and with cells preloaded with Cu(II) or Zn(II) in the presence and absence of external added metal ions. Zn(II) ions inhibit the initial velocity of Mn(II) uptake, increase total Mn(II) accumulated, but do not alter the rate or extent Mn(II) efflux. Cu(II) ions increase both the initial velocity and the net Mn(II) accumulated by glia, with little effect on rate or extent of Mn(II) efflux. These results predict that increases in Cu(II) or Zn(II) levels may also increase the steady-state levels of Mn(II) in the cytoplasmic fraction of glial cells, which may in turn alter the activity of Mn(II)-sensitive enzymes in this cell compartment. PMID- 2097513 TI - Precursors of glutamic acid nitrogen in primary neuronal cultures: studies with 15N. AB - We utilized gas chromatography-mass spectrometry to study the transfer of 15N from [2-15N]glutamine, [15N]leucine, [15N]alanine, or 15NH4Cl to [15N]glutamate and [15N]aspartate in cultured cerebrocortical GABA-ergic neurons from the mouse. Initial rates of 15N appearance (atom % excess) were somewhat higher with 2mM [2 15N]glutamine as a precursor than with 1mM [15N]leucine or 1mM [15N]alanine, but initial net formation (nmol [15N]glutamate/mg protein.min-1) was roughly comparable with all precursors. At steady-state 15N labeling was about two times greater with 2mM [2-15N]glutamine as precursor. The subsequent transfer of 15N from glutamate to aspartate was extremely rapid, the labelling pattern of these two amino acid pools being virtually indistinguishable. We observed little reductive amination of 2-oxo-glutarate to yield [15N]glutamate in the presence of 0.3mM 15NH4Cl. Reductive amination through glutamate dehydrogenase was much more prominent at a concentration of 3.0mM 15NH4Cl. Glutamate formation via reductive amination was unaffected by inclusion of 1mM 2-oxo-glutarate in the incubation medium. These results indicate that glutamate synthesis in cultured GABA-ergic neurons is derived not only from the glutaminase reaction, but also from transamination reactions in which both leucine and alanine are efficient N donors. Reductive amination of 2-oxo-glutarate in the glutamate dehydrogenase pathway plays a relatively minor role at lower concentrations of extracellular ammonia but becomes quite active at 3mM ammonia. PMID- 2097515 TI - Induction of a heat shock gene (hsp70) in rabbit retinal ganglion cells detected by in situ hybridization with plastic-embedded tissue. AB - Elevation of body temperature by 2-3 degrees C induces a 2.7 kilobase hsp70 mRNA species in the rabbit retina within 1 hr. In situ hybridization with thin sections derived from plastic-embedded tissue permitted a higher level of resolution of retinal cell types compared to procedures which involved the use of frozen tissue sections. A prominent induction of hsp70 mRNA in retinal ganglion cells was observed when an hsp70 riboprobe was utilized for in situ hybridization. These results indicate that this neuronal cell type responds rapidly to fever-like body temperatures by inducing one of the major heat shock genes. PMID- 2097516 TI - Chromogranin A in the olfactory system of the rat. AB - The olfactory bulb of the rat contains chromogranin A at a similar level as the adrenal gland or the hypophysis as revealed by immunoblots. Olfactory chromogranin A also displays the same size as chromogranin A of endocrine cells. In the hippocampus and other brain regions, we could not detect chromogranin A by immunoblotting. In contrast, chromogranin A messenger ribonucleic acid (using S1 nuclease protection assays) was observed in all brain regions examined, including the olfactory bulb. By in situ hybridization histochemistry with a complementary ribonucleic acid probe (280 nucleotides), and by immunocytochemistry, chromogranin A synthesis could be localized to cell bodies of the mitral cell layer, of the external plexiform layer and of the periglomerular region of the olfactory bulb. Immunocytochemically, chromogranin A was also detected in the central projection areas of mitral and tufted cells in the primary olfactory cortex and the anterior amygdaloid area but not in the olfactory glomeruli, where the incoming olfactory nerve fibers of the primary olfactory neurons establish synaptic contacts. Taken together the data show that chromogranin A, following biosynthesis in the perikarya of the mitral and tufted cells, is specifically transported into their axonal terminals but not into their primary dendrites. We propose that the rat olfactory system could serve as a model for the study of chromogranin A regulation and function in neurons. PMID- 2097517 TI - Release of endogenous 5-hydroxytryptamine in rat ventral hippocampus evoked by electrical stimulation of the dorsal raphe nucleus as detected by microdialysis: sensitivity to tetrodotoxin, calcium and calcium antagonists. AB - We have utilized the brain microdialysis technique in an attempt to measure excitation-secretion coupled release of endogenous 5-hydroxytryptamine in rat brain in vivo and investigated the pharmacology of the voltage-sensitive calcium channel involved in this process. All experiments were carried out using chloral hydrate anaesthetized rats. Ascending serotoninergic neurons were electrically stimulated using an electrode implanted into the dorsal raphe nucleus. A dialysis probe was implanted into the ventral hippocampus and continuously perfused with artificial cerebrospinal fluid containing the selective 5-hydroxytryptamine uptake inhibitor citalopram (1 microM). Twenty-minute perfusates were analysed for endogenous 5-hydroxytryptamine using high performance liquid chromatography with electrochemical detection. Electrical stimulation (cathodal monophasic 1 ms pulses, 300 microA, 2-10 Hz) of the dorsal raphe nucleus for 20 min induced an immediate release of 5-hydroxytryptamine which lasted for the duration of the stimulus and was frequency-dependent. The calculated amount of 5 hydroxytryptamine release per electrical impulse was constant over the frequency range used. Addition of tetrodotoxin (10 microM) to, or omission of calcium from, the perfusion medium reduced the spontaneous output of 5-hydroxytryptamine by 60 70% and caused a near complete inhibition of the effect of low frequency (3 Hz) electrical stimulation of the dorsal raphe nucleus. Local perfusion with cadmium (30 and 300 microM), which is reported to antagonize both N- and L-type voltage sensitive calcium channels, also caused a pronounced decrease of basal output of 5-hydroxytryptamine and a marked, but not complete inhibition of the effect of nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097518 TI - The role of serotonin release and autoreceptors in the dorsalis raphe nucleus in the control of serotonin release in the cat caudate nucleus. AB - Using a push-pull cannula technique and an isotopic method for estimating [3H]serotonin continuously synthesized from [3H]tryptophan, the effects of changes in the release of serotonin in the dorsalis raphe nucleus on in vivo release of [3H]serotonin in the cat caudate nucleus were investigated. The increase in the release of serotonin in the dorsalis raphe nucleus caused by local application of parachlorophenylethylamine (10(-6) M) reduced striatal [3H]serotonin release. This inhibition in serotonin release in the striatum was blocked by the prior and continuous local superfusion of the dorsal raphe with methiothepin (10(-6) M), a serotonin autoreceptor antagonist. GABA (5 x 10(-5) M) applied to the dorsalis raphe reduced both local and striatal release of [3H]serotonin. However, picrotoxin (10(-5) M), a GABA A receptor antagonist applied locally in the dorsalis raphe nucleus increased [3H]serotonin release while decreasing striatal [3H]serotonin release. This decrease in serotonin release in the striatum was again blocked by continuous superfusion of the raphe with methiothepin. Furthermore, superfusion of serotonergic cell bodies of the dorsalis raphe nucleus with methiothepin alone never altered local release or striatal release of [3H]serotonin. These data strongly suggest that the release of serotonin from the cell body in the dorsalis raphe nucleus phasically controls release of the amine at the axonal nerve ending through serotonergic autoreceptors located on serotonergic nerve cell bodies in the dorsalis raphe nucleus. The origin of the serotonin released in the dorsalis raphe nucleus and the possibility that this type of regulation could be related to changes in nerve impulse conduction of the serotonergic raphe-striatal system are discussed. PMID- 2097520 TI - Midbrain areas required for locomotion initiated by electrical stimulation of the lateral hypothalamus in the anesthetized rat. AB - Locomotor stepping in the Nembutal-anesthetized rat was elicited by electrical stimulation of either of two sites in the right or left posterolateral hypothalamus. Essential midbrain loci were identified by reversibly blocking the elicited locomotion through local injections of the anesthetic procaine (15%, 0.5 microliter). Two types of critical midbrain sites were found. At ipsilateral block sites (n = 21), procaine blocked only that locomotion elicited by ipsilateral stimulation. These sites could be along the course of a direct descending ipsilateral pathway although a possible bidirectional pathway is not to be excluded. At bilateral block sites (n = 21), procaine blocked locomotion elicited by both ipsilateral and contralateral stimulation. These sites could be involved in functions prerequisite for the initiation of locomotion or in the generation of the stepping pattern. Procaine injections in 35 sites had no effect on locomotion. Ipsilateral and bilateral block sites were intermixed and generally located in regions ventral to the midbrain central gray: chiefly the anterior ventromedial midbrain, the pontis oralis nucleus and the pedunculopontine nucleus. Negative sites were located in both the dorsal and ventral midbrain. Ipsilateral block sites were relatively prevalent in the anterior midbrain, indicating that the locomotor initiation signals are lateralized at this level. Bilateral block sites were more prevalent in the posterior levels, suggesting that the initiation signals are proximal to, or interact with, circuits that have a bilateral influence on locomotion. PMID- 2097519 TI - Biochemical and in vivo voltammetric evidence for differences in striatal dopamine levels in inbred strains of mice. AB - High performance liquid chromatography with electrochemical detection and differential pulse voltammetry were used to provide a direct measurement of tissue content of dopamine and its metabolites and extracellular dopamine levels, respectively, in the striata of BALB/c and CBA inbred strains of mice. We found that levels of striatal dopamine and its metabolite, dihydroxyphenylacetic acid, were significantly higher in the CBA strain than in the BALB/c strain, whereas levels of homovanillic acid were not significantly different between the strains. Levels of the dopamine metabolite 3-methoxytyramine, on the other hand, were higher in the BALB/c mice. Dopamine turnover rates were significantly higher in the CBA strain when the homovanillic acid/dopamine ratio was used as an index of dopamine activity. Voltammetric recording showed that the local infusion of K+ in pargyline-treated mice resulted in the immediate appearance of a peak at +85 mV, which has been shown to correspond to extracellular dopamine in the rat. The mean height of this peak detected in vivo following K+ stimulation corresponds to in vitro dopamine concentrations of 25 +/- 8 microM for BALB/c mice and 7 +/- 2 microM for CBA mice. K(+)-stimulated dopamine release in the BALB/c mice could be evoked every 10-15 min with similar magnitude. In contrast, very little dopamine release in CBA mice could be evoked after the first stimulation. Since striatal dopamine levels are higher in CBA mice, these data suggest that (a) BALB/c strain may have more dopamine in the readily releasable pool, whereas the CBA mice have a larger storage pool of dopamine, and/or (b) that dopamine uptake in the CBA mice is much more avid than in BALB/c. PMID- 2097521 TI - Neurons containing messenger RNA encoding glutamate decarboxylase in rat hypothalamus demonstrated by in situ hybridization, with special emphasis on cell groups in medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus. AB - Previous deafferentation studies have suggested that most hypothalamic GABAergic innervation originates from neurons within the hypothalamus. We have investigated the distribution of GABAergic cell groups in the rat hypothalamus by means of the in situ hybridization technique, using a cDNA probe for messenger RNA encoding glutamate decarboxylase. Several major GABAergic cell groups were demonstrated, including cells of the tuberomammillary nucleus, arcuate nucleus, suprachiasmatic nucleus, medial preoptic area, anterior hypothalamic area, the dorsomedial hypothalamic nucleus, perifornical area, and lateral hypothalamic area. The most prominent glutamate decarboxylase mRNA-containing cell groups were located in the medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus, and were composed of small- to medium-sized neurons. Compared to previously well-characterized GABAergic cell groups in the tuberomammillary nucleus, reticular thalamic nucleus, and non-pyramidal cells of cerebral cortex, the cells of these GABAergic groups demonstrated only weak cDNA labelling, indicating that they contain lower levels of glutamate decarboxylase mRNA. Several types of control experiments supported the specificity of this cDNA labelling, and the GABAergic nature of these cell populations was further supported by detection of glutamate decarboxylase and GABA immunoreactivity. Abundance of GABAergic cells in many hypothalamic nuclei indicates that GABA represents quantitatively the most important transmitter of hypothalamic neurons, and may be involved in neuroendocrine and autonomic regulatory functions. PMID- 2097522 TI - Morphological plasticity that occurs in the neurohypophysis following activation of the magnocellular neurosecretory system can be mimicked in vitro by beta adrenergic stimulation. AB - The osmotic stress to rats of replacing drinking water with 2% NaCl for four days (salt loading) led to dramatic ultrastructural morphological changes in the neural lobe of the pituitary, including a decrease in the ratio of glial to neurosecretory terminal coverage of the pericapillary basal lamina. The decrease in the proportion of the basal lamina covered by pituicytes, the specialized astrocytic glial cells of the neural lobe, was due to a decrease in the number of pituicyte processes reaching the pericapillary spaces. The concomitant increase in the proportion of neuronal coverage was due to the combination of an increase in the length of individual nerve terminals and a change in the number of terminals. Similar structural changes to those seen in vivo were produced by incubation of the isolated neural lobe with the beta-adrenergic agonist isoprenaline. A decrease in the ratio of glial to neuronal coverage of the basal lamina was achieved within 1 h and could be blocked by inclusion of the beta adrenergic antagonist propranolol. It is proposed that the morphological plasticity is explained by the active movement of pituicyte cytoplasm. PMID- 2097523 TI - Release of vasopressin from isolated permeabilized neurosecretory nerve terminals is blocked by the light chain of botulinum A toxin. AB - The intracellular action on exocytosis of botulinum A toxin and constituent chains was studied using permeabilized isolated nerve endings from the rat neural lobe. The release of the neuropeptide vasopressin was measured by radioimmunoassay. In the presence of the reducing agent dithiothreitol, the two chain form of botulinum A toxin inhibited vasopressin release induced by 10 microM free calcium. Half maximal inhibition was obtained with 15 nM botulinum A toxin. In the absence of the heavy chain the light chain of the toxin strongly inhibited exocytosis with a half maximal effect of 2.5 nM. The inhibitory effects on secretion could be prevented by incubating the light chain with an immune serum against botulinum A toxin. The heavy chain of botulinum A toxin did not affect vasopressin release. However, it prevented the inhibitory effects of the light chain on stimulated exocytosis. It is concluded that botulinum A toxin inhibits the calcium-dependent step leading to exocytosis by interfering with a target present in the isolated and permeabilized nerve terminals. The functional domain of this neurotoxin, which is responsible for the inhibition of vasopressin release, is present in its light chain. PMID- 2097524 TI - Oxytocin localization and function in the A1 noradrenergic cell group: ultrastructural and electrophysiological studies. AB - Antibodies to oxytocin and noradrenalin were utilized in an immunocytochemical study of the caudal ventrolateral medulla of the rat brainstem. Noradrenalin was visualized by using antibodies to noradrenalin and by means of a silver-gold intensification of diaminobenzidine, whereas oxytocin could be demonstrated in the same section by using the diaminobenzidine precipitate as a marker. At the light microscopic level, oxytocin fibers were densely distributed around the A1 cell bodies. At the ultrastructural level, oxytocin-containing fibers were seen to terminate synaptically onto noradrenalin-containing neurons. Previous studies have shown that electrical stimulation of A1 neurons selectively activates vasopressin-secreting neurons in the supraoptic nucleus. Therefore, separate electrophysiological studies were set up, in which we observed that oxytocin infusions (100-200 pg) into the A1 area enhanced the activity of 16 out of 19 putative vasopressin-secreting neurons and elicited no response from any of 10 oxytocin-secreting neurons. This finding suggests that some of the parvicellular neurons in the paraventricular nucleus of the hypothalamus, from which the A1 neurons derive their oxytocin innervation, can activate the A1 cell group via this peptidergic neurotransmitter. One of the consequences of A1 neuronal activation is enhanced firing of hypothalamic supraoptic (and paraventricular) vasopressin-secreting neurons, and a consequent rise in plasma vasopressin. PMID- 2097525 TI - Expression of beta-preprotachykinin mRNA and tachykinins in rat dorsal root ganglion cells following peripheral or central axotomy. AB - The changes in gene expression and protein synthesis induced in neurons by axotomy usually lead to increased production of axon constituents and decreased production of molecules related to neurotransmission. Exceptions to this generalization occur, however, and it is unclear whether the injury itself changes the pattern of synthesis or whether individual mechanisms regulate the synthesis of the various axonal components. We used in situ hybridization histochemistry and immunocytochemistry to compare the changes in L4 and L5 rat dorsal root ganglion neuron levels of preprotachykinin mRNA and tachykinin peptides caused by sciatic nerve injury with those caused by dorsal root injury. Both lesions elicit regeneration, although only the axotomized peripheral processes re-establish functional contact with their targets. In the contralateral, intact dorsal root ganglia approximately 17% of neurons contained detectable levels of both mRNAs and peptides. Sciatic nerve section decreased by 70% the number of neurons labeled for preprotachykinin mRNA at three days post operatively. Not all cells in the ganglion are axotomized by the sciatic nerve lesion; grain counts over the cells spared by the lesion showed an increased level of labeling, possibly a result of collateral sprouting by these spared cells. By two weeks, the number of cells labeled for preprotachykinin mRNA had decreased to 80% of control levels. The numbers of neurons labeled for tachykinin peptides decreased more slowly and reached approximately 50% of control numbers at two weeks. By six months post-operatively, when regeneration is largely complete, the number of neurons containing both mRNAs and peptides returned to normal. In contrast, dorsal root section did not elicit a decrease in the number of neurons labeled either for the mRNAs or the peptides at any of the post operative intervals examined. These results indicate that axotomy is not the stimulus that elicits changes in the expression of genes coding for tachykinins. Evidence is considered indicating that interruption of the supply of peripherally derived nerve growth factor may be responsible for the changes in gene expression for tachykinins after axotomy. PMID- 2097526 TI - Differential effects of antiepileptic drugs and beta-carbolines on seizures induced by excitatory amino acids. AB - Agonists acting at subtypes of glutamate receptors, N-methyl-D-aspartate, kainate and quisqualate, induce convulsions in rodents. Clonic seizures induced in mice by intracerebral administration of N-methyl-D-aspartate, kainate or quisqualate were used to study the anti- and proconvulsant potential of antiepileptic drugs and beta-carbolines. Systemic administration showed that the benzodiazepines clonazepam and midazolam blocked convulsions induced by kainate and had no effect on seizures triggered by N-methyl-D-aspartate and quisqualate. In contrast, diazepam blocked convulsions induced by either excitatory amino acid, as did valproate. The benzodiazepine receptor agonist beta-carboline ZK 93423 blocked convulsions induced by kainate but had no effect on seizures induced by N-methyl D-aspartate or quisqualate. The antagonist beta-carboline ZK 93426 did not affect convulsions induced by excitatory amino acids, while the inverse agonists FG 7142 and ethyl-beta-carboline-3-carboxylate increased the sensitivity of mice to kainate. Phenobarbital and 2-chloroadenosine protected mice against seizures induced by quisqualate and kainate, while baclofen was active against convulsions produced by kainate. MK-801 selectively blocked convulsions induced by N-methyl-D aspartate, and enhanced the susceptibility of mice to seizures triggered by kainate and quisqualate. Ethosuximide increased the susceptibility of mice to N methyl-D-aspartate and had little or no effect on other types of seizures. Diphenylhydantoin enhanced the convulsant potential of quisqualate. Trimethadione and carbamazepine did not affect convulsions induced by N-methyl-D-aspartate, kainate or quisqualate. Intracerebral administration of midazolam protected mice against seizures induced by kainate. Ethosuximide increased the susceptibility of mice to N-methyl-D-aspartate, while diphenylhydantoin to quisqualate convulsions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097527 TI - Effect of acetylcholine on single Ca2(+)-activated K+ channels in bovine chromaffin cells. AB - The single channel current amplitudes of "maxi" Ca2(+)-activated K+ channels from bovine chromaffin cell membranes are reduced when acetylcholine is applied to the internal surface of the membrane, which can be explained by a fast channel block. The block is concentration dependent with moderate affinity. It becomes progressively greater with depolarization although the voltage dependence is not pronounced. Acetylcholine reduces the probability of the open state in the same concentration range and in an essentially voltage independent manner. The changes in the channel kinetics are complex. Whilst the long component of the open intervals is shortened (by 48%; from 9.5 to 5.1 ms), the long component of the closed intervals is prolonged (by 96%; from 45 to 89 ms). The short components (open and closed) are essentially unaffected. Short open intervals are reduced by 4% (from 1.09 to 1.05 ms), whilst short closed intervals are reduced by 5% (from 2.3 to 2.2 ms). These changes in the channel kinetics can be explained at least partly if one assumes that acetylcholine, in addition to its fast channel blocking activity, acts also as a slow blocker. If so, both binding sites are expected to be located close to the mouth of the channel pore. Alternatively, acetylcholine may be affecting the gating mechanism, presumably by interfering with the Ca2+ binding. PMID- 2097528 TI - Response properties and descending control of rat dorsal horn neurons with deep receptive fields. AB - The study was designed to obtain information on the spinal processing of input from receptors in deep somatic tissues (muscle, tendon, joint). In anaesthetized rats, the impulse activity of single dorsal horn cells was recorded extracellularly. In a pilot series, the proportion of neurons responding to mechanical stimulation of deep tissues was determined: 46.7% had receptive fields in the skin only, 35.5% could only be driven from deep tissues (deep cells), and 17.7% possessed a convergent input from both skin and deep tissues (cutaneous deep cells). In each category, neurons with low and high mechanical thresholds were encountered. Experiments employing a reversible cold block of the spinal cord showed that deep cells with high threshold were subject to a stronger descending inhibition than low-threshold deep cells. In cutaneous-deep neurons the input combination high-threshold cutaneous and high-threshold deep was the most frequent one (48.7% of the cutaneous-deep cells). In these presumably nociceptive cells the descending inhibition had a differential action in that the input from deep tissues was more strongly affected than was the cutaneous input to the same neuron. The recording sites of the neurons with deep input were located in the superficial dorsal horn and in and around lamina V. The results suggest that in the rat a considerable proportion of dorsal horn cells receives input from deep nociceptors and that this input is controlled by descending pathways in a rather selective way. PMID- 2097530 TI - The influence of transplantable epithelioma Guerin on myoelectrical activity. PMID- 2097529 TI - Motor response of the human isolated colon to capsaicin and its relationship to release of vasoactive intestinal polypeptide. AB - The aim of this study was to obtain indirect evidence of the presence of capsaicin-sensitive afferents in the human colon by studying the motor response to capsaicin of longitudinal strips from the human isolated taenia coli in parallel to the ability of capsaicin or KCl to induce peptide release from the human superfused colon. Capsaicin (1 microM) evoked a relaxation of the taenia, approaching 60-80% of the response to isoprenaline. Tachykinins evoked contractions of the taenia, while calcitonin gene-related peptide induced a relaxation. Neither tachyphylaxis to calcitonin gene-related peptide nor preincubation with an anti-calcitonin gene-related peptide serum did block the response to capsaicin which was also unaffected by tetrodotoxin, apamin, naloxone or an anti-galanin serum. Vasoactive intestinal polypeptide produced a concentration-dependent tetrodotoxin-resistant relaxation which was shifted rightward in the presence of anti-vasoactive intestinal polypeptide serum. The anti-vasoactive intestinal polypeptide serum reduced the response to capsaicin and application of capsaicin prevented the ability of anti-vasoactive intestinal polypeptide serum to block exogenous vasoactive intestinal polypeptide. Capsaicin (1 microM) evoked a significant release of vasoactive intestinal polypeptide-like immunoreactivity from the superfused muscle but not mucosa of the human colon. A significant vasoactive intestinal polypeptide-like immunoreactivity release was also observed in response to KCl (80 mM). KCl but not capsaicin evoked a significant release of neurokinin A-like immunoreactivity from colonic muscle and mucosa. No significant release of either substance P-, neuropeptide Y-, galanin- or calcitonin gene-related peptide-like immunoreactivity was detected in response to capsaicin or KCl although detectable levels of each peptide were evident in tissue extracts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097532 TI - Basement membrane component changes during experimental skeletal muscle degeneration and regeneration. PMID- 2097531 TI - [Chronic eosinophilic meningitis caused by cysticercosis cerebri]. AB - The authors describe a case of encephalomeningitis chronica eosinophilia in a 60 year-old woman. The etiology was not investigated clinically. The autoptic diagnosis was cerebral cysticercosis. PMID- 2097534 TI - Paraneoplastic cerebellopathies in infants. PMID- 2097533 TI - Regenerative capability of denervated rat skeletal muscle: ultrastructural study. PMID- 2097535 TI - Cerebral ischemia reduces the density of 125I-iodipine binding sites in the rat brain. PMID- 2097536 TI - Protective effect of the calcium entry blocker nimodipine on hippocampal rat cultures submitted to anoxia. PMID- 2097537 TI - The blood-brain barrier (BBB) permeability in multiple sclerosis. PMID- 2097538 TI - [The influence of CCNU (lomustine) on the neurosecretion of hypothalamic nuclei and the neurohypophysis during early stages of extrauterine development of the rat]. AB - The hypothalamo-neurohypophyseal neurosecretory system was investigated in 8-, 15 and 30-day-old rats subjected to three intragastric doses of CCNU - 12.5 mg/kg b. wt. each on the 3rd, 5th and 7th day after birth. Neurosecretory neurons in the hypothalamus were visualized in the paraffin sections by the immunoenzyme (PAP) technique using antibodies against neurophysin and by Gomori chrome hematoxylin staining. Accumulation of neurophysin was observed in these cells after treatment with CCNU. Karyometric measurements showed an increase of the mean nuclear cross-section area in PVN neurons in 8-day-old rats exposed to CCNU. In four experimental rats disseminated intracerebral hemorrhagic foci were present. Plasma osmolality was far below the normal values on the 8th day, on the 15th day of life it shifted to hyperosmolality and returned to normal at the age of 30 days. Discussion of the results leads to the conclusion that the increase of the neurosecretory function observed in this experiment was secondary to vasogenic changes. PMID- 2097539 TI - [Histology of the central nervous system in rats after intensive chronic ethanol intoxication]. AB - The influence of intensive chronic intoxication with ethanol on adult Wistar rats was investigated. The animals received through a stomach pump 5 ml of 40% ethyl alcohol solution daily for three months. Structural lesions of the CNS observed in the light microscope consisted of acute and chronic edematous changes with infiltration of mononuclear cells and presence of lymphocytic-microglial nodules and myelin discoloration. Sclerotization of nerve cells with reactive gliosis was also noted in the CA1 sector of ventral hippocampus. The pattern of changes is comparable with the most frequently observed pathological abnormalities observed in the CNS of humans after alcohol abuse. PMID- 2097540 TI - Dynamics of pathomorphological changes in the brain of rats after clinical death. PMID- 2097541 TI - Some new trends in studies of postresuscitation brain pathology. PMID- 2097542 TI - Postischemic halothane anesthesia and motor hyperactivity in gerbil. PMID- 2097543 TI - Ultrastructural findings in the gerbil hippocampus after brief global ischemia and long survival times. PMID- 2097544 TI - Some individual peculiarities of brain energy metabolism and their changes in the condition of brain ischemia. An in vivo 31P nuclear magnetic resonance study. PMID- 2097545 TI - Experimental treatment with prostacyclin of global cerebral ischemia in rabbit- new data. PMID- 2097546 TI - Late changes in cerebral hemispheres after perinatal anoxic damage. PMID- 2097547 TI - Infantile brain damage due to hypoxia with special reference to formation of dendritic spines. PMID- 2097548 TI - Myelin proteins in the late period after moderate hypoxia. PMID- 2097549 TI - Free fatty acids of cerebral white matter in the late period after severe hypoxia. PMID- 2097550 TI - Morphometric studies of the myelin-oligodendroglia complex in the late period after hypoxia. PMID- 2097551 TI - Karyometric analysis of vascular endothelia in the fornix columns of rat brain in the late period after hypoxia. PMID- 2097552 TI - The role of hypoxia in diseases of peripheral nerves. PMID- 2097553 TI - Fibrinogen degradation products in serum and cerebrospinal fluid in cerebrovascular diseases. PMID- 2097554 TI - Influence of moderate hypoxia on the composition of fatty acids in myelin lipids. PMID- 2097555 TI - Comparative evaluation of blood vessel endothelia in white matter structures of rat brain following hypoxia. PMID- 2097556 TI - Myelin proteins of senile rat brain. PMID- 2097557 TI - Karyo- and cytophotometric studies on vascular endothelia in the white matter of the aging rat brain. PMID- 2097558 TI - [Progress in the diagnosis of unknown primary neoplasms]. AB - About 5% of tumours clinically begin as unknown origin metastases involving some difficult diagnostic and therapeutic problems. In these cases the main goal is the formulation of the diagnosis as rapidly as possible because only about 10-15% of diagnosed patients are susceptible of treatment. Between 1973-1989 we observed 59 patients with unknown origin metastases. The diagnosis has been expressed in 5 patients by means of histochemical and immunohistochemical analysis, in 6 patients by means of radiologic and instrumental tests and in 3 patients spontaneously after 2-3 months. PMID- 2097559 TI - [The prognostic value of Jass' histopathological classification of cancer of the left colon and rectum]. AB - Histological material from 121 patients who underwent surgery for cancer of the left colon and rectum was reexamined by two pathologists according to criteria put forward in Jass' histopathological classification. A prevalence of Jass' grades II (36.4%) and III (47.9%) were observed in this series. There was no correlation between the site of neoplasia but there was a clearly increased incidence of advanced stages C and D according to Dukes-Kirklin's classification within Jass' grades II, III and IV (p less than 0.005) and growth pattern, but not for the configuration of tubules. The new histopathological model proved to be more reliable in prognostic terms in the case of cancer of the rectum compared to that of the left colon, but at present its clinical significance is limited to specifying the site and stage of the neoplasia. The latter was found to be the most reliable prognostic parameter. PMID- 2097560 TI - [Autotransfusion in vascular surgery]. AB - This report describes 51 vascular patients with peripheral vascular disease treated intraoperatively by means of the autotransfusion apparatus with a minimum of 750 cc of reinfused blood. An early decrease of Hct, Hb, RBC, fibrinogen and Plt count was observed without any significant coagulation disorder. PMID- 2097561 TI - [The use of the expanded PTFE (Gore-Tex) prosthesis with progressive preoperative pneumoperitoneum in the repair of massive inguinal hernias and large laparoceles]. AB - The authors present two cases of massive inguinal hernia and large recurring abdominal wall defect, in which hernia repair and wall reconstruction is made possible thanks to the use of large patches of expanded PTFE (Gore-Tex). The authors moreover insist on the efficacy of using the progressive preoperative pneumoperitoneum as a technic to prepare the patient to surgery together with respiratory physiotherapy, for the purpose of preventing the occurrence of unfavourable repercussions falling upon the cardiorespiratory apparatus with the repositioning into the abdomen of the hernias. PMID- 2097563 TI - [The value and limits of the follow-up in patients operated on for breast carcinoma. Our experience]. AB - The aim of follow-up is essentially that of diagnosing possible recidivation at a relatively early and practically asymptomatic stage in order to optimise the results of appropriate treatment and to improve both the overall survival rate and the patient's quality of life. In spite of the correct and systematic planning of controls, the authors underline that in their experience only 64.7% of relapses are diagnosed during the asymptomatic phase. However, the authors have confirmed that the expectation of relapse has a barely significant influence on survival. After five years of first receiving treatment, 83% of patients with relapses diagnosed in a symptomatic phase had died, compared to 81.7% of those with relapses diagnosed during the asymptomatic phase. In conclusion, in spite of the fact that it is possible to obtain early diagnosis of recidivation during follow-up, it is equally true that this has no influence at all on the survival rate. However, irrespective of these results, the authors maintain that it is useful to follow patients undergoing breast surgery through a periodic follow-up to evaluate the evolution of disease and acquire an increasingly precise and definite knowledge of its natural history. The authors put forward a protocol for follow-up in which patients are divided into groups on the basis of lymph node status and pre- or postmenopause. PMID- 2097562 TI - [The value of the triad: clinical examination, mammography and needle aspiration cytology in the diagnosis of breast carcinoma. Our experience]. AB - Based on the authors' personal experience of the use of the triad, clinical examination, mammography and needle-aspiration cytology, in the strategic diagnosis of breast cancer, the paper emphasizes the importance of early diagnosis as the sole means of obtaining an improved outcome. Using this integrated methodology the authors have obtained a specificity of 99%, sensitivity of 97.8%, and a diagnostic accuracy and prognostic value for positive tests of 98%. In conclusion, the authors affirm that the comparative interpretation of clinical examination, mammography and cytology appears to be an extremely efficacious and reliable method for the diagnosis of the nature of breast nodules. PMID- 2097564 TI - [The current value of the whipstitch suture following carotid TEA]. AB - There is no consensus of opinion regarding the type of suture to be used followed carotid TEA. The paper reports a study carried out in 123 operated patients who were followed for a variable period ranging from 6 months to 4 years with six monthly controls using B-mode echotomography, supplemented by digital angiography via a venous route if necessary. A direct suture was used in 92 of the patients, while a venous patch was applied in the remaining 31. Subsequent controls revealed a relative frequency of restenosis of a fundamentally benign nature at a point which was proximal or distal to TEA. In addition, the study showed that continuous suture may be valid in male patients but doubts continue to exist regarding its use in female patients. In the latter, it is therefore preferable to encourage a more widespread use of the venous patch. PMID- 2097565 TI - [The prevention of deep venous thromboses after radical or modified mastectomy interventions]. AB - With the aim of preventing deep vein thrombosis after radical or modified mastectomy, 100 patients were randomly assigned to one of two different groups: the first group was treated with defibrotide (400 mg b.i.d. e.v.) starting from the day before the operation and continuing for the following seven days. The second group was given calcium heparin (5,000 IU b.i.d. by s.c. route) from day 0 to the 7th post-operative day. Neither side effects nor DVT or PE were observed. The quantity of fluids from the drainages rapidly decreased in both groups from the first day to the third one, while the quantity of blood cells was negligible starting from the second post-operative day. On this basis defibrotide may be considered an effective and well tolerated drug for the prevention of DVT. PMID- 2097566 TI - [Retroperitoneal ruptures of the duodenum. Our experience]. AB - The authors describe a case of retroperitoneal rupture of the duodenum following blunt abdominal trauma. The aetiology, symptomatology of these lesions are discussed and treatment is stressed. Duodenal fistula continues to be a serious postoperative complication. Primary repair with drainage is the preferred treatment. Gastrostomy, internal decompression and feeding jejunostomy are usefully added in the most severe duodenal injuries. PMID- 2097567 TI - [Infarct of the sigmoid: a rare cause of peritonitis. Apropos a clinical case]. PMID- 2097568 TI - [Mesenteric panniculitis of the sigmoid. A case report and review of the literature]. AB - Mesenteric panniculitis is an extremely rare disease in which the normal fatty architecture of the mesentery is replaced by fibrosis, necrosis and calcification. One hundred twenty-four cases of mesenteric panniculitis have been described in the literature; only five of these involved the sigmoid mesentery. The following case report is of mesenteric panniculitis confined to the sigmoid colon. Symptomatology, pathology, treatment and outcome of this disorder are discussed. It seems that this disease is a well established clinical entity of unknown etiology with a benign course and favorable outcome. Radical surgical treatment is not advised. If mesenteric panniculitis is encountered at operation, biopsy to establish the diagnosis is indicated. If the mechanical effects are significant, they should be corrected. PMID- 2097569 TI - [A case of cystic lymphangioma of the liver]. AB - Here is a case report about a cystic lymphangioma of the liver, a rare benign tumor, extremely difficult to diagnose with certainty in spite of the wide range of examinations today available. Surgical intervention is still the most important means to achieve the final diagnosis. The authors also provide a discussion about the pathogenesis and the clinical manifestation of the disease. PMID- 2097570 TI - [Stenosis of the popliteal artery due to adventitial cysts]. AB - The authors report a case of popliteal artery adventitial cystic disease. They discuss diagnosis and treatment. PMID- 2097571 TI - Cells of origin of ascending and descending as well as branching fibers in the cervical spinal cord of the pigeon. AB - Ascending and descending projections of spinal neurons (cervical enlargement) were studied with the retrograde transport of horseradish peroxidase (HRP) and with the fluorescent tracers Fast blue and rhodamine isothiocyanate (single and double labeling). Ascending and descending projections arise from the same laminae of the spinal grey except for neurons in contralateral lamina I and avian cervical Clarke's column which have ascending fibers only. A significant number of cervical nucleus proprius neurons (lamina IV) descends to the lumbar enlargement. Neurons with branching fibers were rare (less than 10 per cent). PMID- 2097572 TI - Stimulation of the nucleus basalis of Meynert does not influence glucose utilization of the cerebral cortex in anesthetized rats. AB - The effect of focal electrical stimulation of the nucleus basalis of Meynert (NBM) on the regional cerebral metabolic rate for glucose (rCMRglc) was examined in halothane-anesthetized rats using the quantitative [14C]2-deoxy-D-glucose method. The stimulation of the unilateral NBM (with parameters of 200 microA, 0.5 ms, 50 Hz for 45 min) did not influence rCMRglc in any brain regions except for the stimulated NBM itself. In cerebral cortex ipsilateral to the NBM stimulated, the regional cerebral blood flow (rCBF) was increased by the NBM stimulation through the stimulated period, while rCMRglc was not increased. These results suggest that the increase in rCBF in the cortex following focal electrical stimulation of the NBM is not a consequence of an increase in rCMRglc in the cerebral cortex. PMID- 2097573 TI - The central inhibitory effect of interleukin-1 on gastric acid secretion. AB - The effect of interleukin-1 (IL-1) on gastric secretory functions was examined in pylorus-ligated conscious rats. Intracisternal (i.c.) injection of IL-1 beta (1 100 ng) induced dose-related, long-lasting inhibition of gastric acid output, which was due to the reductions of both the amount and the acid concentration of the gastric juice. A much higher dose of IL-1 alpha was required to achieve identical effects on gastric acid secretion when it was given by intravenous routes. The i.c. injection of IL-1 alpha also had an inhibition of gastric secretion. This inhibitory effect of i.c. applied IL-1 beta on gastric acid secretion was completely abolished in indomethacin-pretreated animals but not in reserpine-pretreated ones. These results suggest that IL-1 may have an inhibitory action on the regulation of gastric secretory functions by its central action which is dependent on the eicosanoid metabolism. PMID- 2097574 TI - Variations by layers and developmental changes in expression of telencephalin in the visual cortex of cat. AB - The expression of telencephalin in visual cortex of cat and monkey was studied immunohistochemically. In adult cats and monkeys, immunoreactivity to a polyclonal antibody raised against telencephalin was especially low in layer IV, which receives massive afferent input from the thalamus. In kitten visual cortex, the antibody bound both layer IV and other cortical layers during the most sensitive period for ocular dominance plasticity. Outside the sensitive period, the staining of layer IV was selectively reduced. These findings suggest that the expression of telencephalin is developmentally regulated during the early period and may play a role in regulating plasticity during the sensitive period. PMID- 2097575 TI - Opiates inhibit pedunculopontine neurones in guinea pig brainstem slices. AB - Intracellular recordings were obtained from pedunculopontine neurones in guinea pig brainstem slices. These cells were characterized by a broad action potential, an A-like conductance and fired spontaneously in a regular manner. These neurones were inhibited by bath-application of both carbachol and serotonine at concentrations of 10(-4) M. Opioid peptides induced a dose-dependent hyperpolarization and a reduction in the spontaneous firing. These latter effects could be blocked by the opiate antagonist naloxone and were direct as they persisted in presence of tetrodotoxine or high magnesium/low calcium-containing salines. They were mediated by an opiate receptor of the mu type since they were obtained with the mu-preferring enkephalin analogues FK 33-824 and DAGO, but neither with the delta nor the kappa analogues such as DPLPE or U-50,488. PMID- 2097576 TI - Vasopressor effects of intracerebroventricular injections of PEC-60, a novel porcine 60-residue intestinal peptide, in the awake unrestrained male rat. AB - Intracerebroventricular injections (140-4300 pmol) of a 60-residue polypeptide (now designated PEC-60) isolated from pig intestine produced a dose-dependent increase (peak action 21% +/- 2; ED50 value of 1.7 nmol for the peak effect) in mean arterial blood pressure (MAP) in the awake, unrestrained male rat. The heart rate (HR) was significantly reduced with the highest doses used (1400 and 4300 pmol). The pancreatic secretory trypsin inhibitor (PSTI), with a high degree of sequence similarity to PEC-60, did not significantly change MAP and HR (4300 pmol). These results may indicate a biological role for the putative PEC-60-like peptide demonstrated within central catecholamine cardiovascular neurons. PMID- 2097577 TI - Fibronectin involvement following herpes simplex infection of cultured rat astrocytes. AB - To evaluate the potential impact of a strongly neurotropic virus on the matricial fibronectin (FN) of a given neural cell type, first subculture of rat astrocytes were inoculated with either a low (0.1-0.5) or a high MOI (10-100) of Herpes simplex virus-type 1 (HSV-1). Infected samples, as well as matched controls, were harvested from 12 to 72 h post-inoculation and processed for extracellular FN labeling by the peroxidase-antiperoxidase (PAP) method. Following low MOI, multinucleated cell formation and syncytial development drastically modified peripheral FN, since the typical loose network was largely replaced by a patch like appearance. At high MOI, when viral action caused further cytoplasmic retraction leading to rounded or stellate cells, the FN pattern was remarkably altered, even with total FN loss around highly retracted cells. It may be concluded that a virus such as HSV-1, capable of modifying astrocyte morphology, induces a redistribution or loss of pericellular FN. PMID- 2097578 TI - Influence of intensity of illumination during the light period on diurnal variations of pineal indoles in rats and mice. AB - The diurnal variations of pineal indoles in New-Zealand Black (NZB) mice and Wistar rats were determined by HPLC fluorometry. Pineal N-acetylserotonin (NAc5HT) in NZB mice showed a marked diurnal variation, but no melatonin (MLT) was detected at any time of day or night. The night-time increases of NAc5HT in NZB mice and MLT in Wistar rats were delayed about one hour in animals kept under illumination of high intensity (2000 lux) during the light period (12 h) compared with those in animals kept under illumination of low intensity (10 lux). These results suggest that the intensity of illumination during the light period affects the diurnal rhythms of pineal indoles in experimental animals. PMID- 2097579 TI - K(+)- and temperature-evoked taurine efflux from hypothalamic astrocytes. AB - Hypothalamic astrocytes in culture released taurine, a suspected inhibitory amino acid neurotransmitter/neuromodulator/osmoregulator, in response to isoosmotically increasing extracellular K+ in a dose-dependent fashion. In the absence of added Ca2+, basal release levels rose to approach those obtained after exposure to 60 mM K+ in the presence of 2.5 mM Ca2+, and were only partially lowered by the addition of 10 mM Mg2+. Stimulation with K+ (60 mM) did not further increase taurine efflux above the high basal levels seen in the absence of Ca2+. Under standard conditions complete replacement of Na+ with choline Cl had little effect on basal taurine release, but reduced K(+)-evoked (60 mM) efflux by 60%. The temperature dependence of the basal levels of taurine released from hypothalamic astrocytes was similar to that seen for cultured cerebellar astrocytes and neurons over the range 5-50 degrees C. Taurine release increased from 5 to 15 degrees C, remained constant between 15 and 33 degrees C, decreased between 33 and 37 degrees C and increased thereafter. The infection point of increased basal taurine release seen around 37 degrees C (most prominent in astrocytes), may be of physiological significance. Results presented also show that the ion (Na+, Ca2+ and K+) sensitivities of taurine efflux for cultured hypothalamic astrocytes are similar to those previously reported for cultured astrocytes from the cerebellum. PMID- 2097580 TI - Lack of age effects on human brain potentials preceding voluntary movements. AB - We examined age effects on Movement related potentials (MRPs) in 13 young (mean age = 29.3 years) and 13 old (mean age = 67.2 years) normal adults in right, left and bimanual self-paced button press conditions. Both the groups generated a slowly rising readiness potential (RP) at about 1000 ms, a negative shift (NS') at about 450 ms and a motor potential (MP) at about 100 ms prior to movement. The RP was symmetrical, bilaterally distributed and maximal at the vertex in all conditions in both the groups. Both the groups produced contralaterally enhanced NS' and MP components in unimanual conditions. In contrast to prior reports, topographical distribution, onset latency and mean amplitude were comparable between young and old subjects for the RP, NS' and MP components of the MRP. The results indicate that motor programming as indexed by MRPs is unaffected by normal aging. PMID- 2097581 TI - Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease. AB - Alzheimer senile plaques are comprised of extracellular deposits of beta-amyloid. The cell type responsible for the secretion of this amyloid, however, is unknown. In the present study, compact amyloid 'stars' and the cellular elements directly apposed to them were examined at the ultrastructural level. In many cases, amyloid fibrils were closely interdigitated with the plasma membrane of cells with dark cytoplasm, dense bodies and distinctive nuclei. These cells were morphologically identified as microglia, the resident macrophages of the brain. Previous work has described an identical morphologic association between macrophages and several types of systemic and cerebral amyloidoses. Taken together, these data suggest that beta-amyloid may be secreted by microglia. PMID- 2097582 TI - Denervation-induced inflammation in the rat. AB - We report that section of the sciatic and saphenous nerves, in the hindlimb of the rat, evokes an inflammatory response in the denervated tissue that can be distinguished from the previously described peptide-mediated neurogenic inflammation. This novel form of neurogenic inflammation has a very delayed onset (9.75 +/- 2.1 h, mean +/- S.E.M., n = 8), persists for more than 30 h, and is characterized by a marked neutrophilic cellular infiltrate. These features cannot be mimicked by electrical stimulation of the peripheral nerve and are not prevented by either prior application of local anesthetics to the nerve lesion site or by neonatal treatment with capsaicin. PMID- 2097583 TI - The effects of adenosine on the development of long-term potentiation. AB - In previous work we found that a brief period of hypoxia occurring within 1-2 min of high-frequency stimulation disrupts the development of long-term potentiation (LTP) in the CA1 field of rat hippocampal slices. We now report that extracellular application of adenosine if applied within 1 min but not 5 min after high-frequency stimulation similarly prevents LTP. Adenosine was ineffective if DPCPX (1,3-dipropyl-8-cyclopentyl-xanthine), a selective antagonist of adenosine A1 receptors, was present. The post-stimulation application mode excludes the possibility that adenosine interferes with NMDA receptor activation and its role in initiating LTP. It suggests instead that changes in intracellular control systems linked to adenosine receptors can during a brief vulnerable period interrupt the biochemical processes leading to the expression of long-term potentiation. PMID- 2097584 TI - Parvalbumin immunoreactivity in the central auditory system of the gerbil: a developmental study. AB - Changes in parvalbumin-like immunoreactivity were studied during ontogenetic development of the central auditory system of the Mongolian gerbil (Meriones unguiculatus). The nucleus of the trapezoid body contained cells that could be stained on the day of birth while in the superior olivary complex, prominent staining of cell somata was only found at P15 (postnatal day 15). Neurons located in the ventral nucleus, in the dorsal nucleus of the lateral lemniscus and in the inferior colliculus developed parvalbumin immunoreactivity mostly between P11-P15 (ventral nucleus), P15-P19 (dorsal nucleus) and P15-P19 (inferior colliculus), respectively. The accumulation of PV correlates reasonably well with the functional maturation of the neurons in these areas. PMID- 2097585 TI - Distribution of Met-enkephalyl-Arg-Gly-Leu in rat larynx: partial coexistence with vasoactive intestinal polypeptide, peptide histidine isoleucine and neuropeptide Y. AB - Using light microscopic (LM) enzyme-immunohistochemistry on deparaffinized adjacent sections Met-enkephalyl-Arg-Gly-Leu (ME-RGL) immunoreactivity was found to partially coexist with immunoreactive neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in intrinsic laryngeal neurons of the rat. Further ME-RGL-immunoreactive (ir) fibres were found around glands in the subepithelium, in connective tissue of striated muscle and in the perichondrium, as well as around arterial and venous blood vessels. They frequently contacted mast cells and macrophages. The presence of ME-RGL indicates pro-enkephalin-related origin of this novel laryngeal opioid system. From the specific target relations and close interrelations of fibres staining for opioids with those staining for the other peptides--which are known to be more or less characteristic of the sympathetic (NPY), parasympathetic (VIP, PHI) and sensory (calcitonin gene-related peptide; CGRP) subdivisions of the peripheral nervous system--we deduce that opioid/non-opioid interactions might co control various laryngeal functions, e.g. glandular secretion, blood flow, immune and inflammatory responses and/or might be of relevance in trophic mechanisms. PMID- 2097586 TI - Exogenous aluminum accumulates in the lysosomes of cultured rat cortical neurons. AB - In order to study the intracellular localization of aluminum, 0.01% AlCl3 was added to rat cerebral organotypic cultures following 14 days incubation in a standard medium. The cultures were maintained in the aluminum (Al)-containing medium for 1 or 3 days. Subsequently, electron probe X-ray micro-analysis (EPXMA), was used to localize aluminum in the neurons. The Al was found in the cells as early as after 1 day of AlCl3 exposure. The Al was detected exclusively in the neuronal lysosomes, in 66% (1 day exposure) and 97% (3 days) of the measured lysosomes. This localization was confirmed by laser microprobe mass analysis (LAMMA) measurements. Our results demonstrate an Al localization in the neurons, exposed to exogenous Al, different from that in the brains of patients with Alzheimer's disease. PMID- 2097587 TI - Unusual features of GABA responses in layers IV-V neurons of neocortex. AB - Perikaryal application of GABA produced a hyperpolarization and increased the input conductance in neurons of layers IV-V of neocortex (guinea pig). This response faded during brief applications and had a long duration when the application period was increased from 4s to greater than 10 s. The sensitivity of the first response to blockade by the selective antagonist, bicuculline, indicated a mediation by gamma-aminobutyric acid-A (GABAA) receptors. The longer duration response was mimicked to some extent by the GABAB agonist, baclofen. Dendritic application of GABA induced a depolarization and a conductance increase - a response which was not particularly sensitive to antagonism by bicuculline. The depolarizing response also did not have a clearly defined reversal potential and may be a consequence of complex changes in membrane conductance, possibly for Cl and Ca or Na. Fading in both types of responses may result from a concomitant postsynaptic activation of a Cl conductance with Na-dependent GABA uptake. PMID- 2097589 TI - Pneumotaxic mechanisms in the non-human primate: effect of the N-methyl-D aspartate (NMDA) antagonist ketamine. AB - We tested the possible involvement of N-methyl-D-aspartate (NMDA) receptors in the central inspiratory-termination mechanism in non-human primates. Inspiratory bursts were recorded from the phrenic nerve in Macaca fascicularis monkeys paralyzed and ventilated by means of a servoventilator driven by the inspiratory discharge of the phrenic nerve. The central inspiratory termination mechanism was tested by withholding lung inflation. This transiently suppressed the vagal feedback from the lungs which produces inspiratory off-switching independent from the central mechanism. Under anaesthesia with ketamine, a potent NMDA antagonist, non inflation increased inspiratory time to 4s (1s with lungs inflated) whereas no such effect was observed during halothane anaesthesia. We conclude that the termination of inspiration in primates is controlled via central mechanisms in which NMDA receptors are involved. PMID- 2097588 TI - Distribution and co-existence of Met-enkephalin-like and mesotocin-like immunoreactivity in the neural lobe of the pituitary of the frog. AB - Content and distribution of Met-enkephalin (Met-ENK)-like immunoreactivity in the hypothalamo-hypophysial system of bovine, rat and frog were examined using specific radioimmunoassay and immunohistochemistry. Ultrastructural localization and co-existence of Met-ENK-, mesotocin (MT)- and vasotocin (VT)-like immunoreactivity in the neural lobe of the frog pituitary was examined by a method combining pre-embedding peroxidase-antiperoxidase immunostaining for Met ENK with post-embedding immunocolloidal gold staining for MT or VT. The highest concentrations of immunoassayable Met-ENK were present in the neural lobe of the pituitary of the frog. In addition to nerve fibers showing only MT-like or Met ENK-like immunoreactivity, nerve fibers containing neurosecretory granules showing both MT- and Met-ENK-like immunoreactivities were very rich. But VT-like and Met-ENK-like immunoreactivity was confirmed separately in different axon terminals. PMID- 2097590 TI - Restraint stress and adrenalectomy do not affect the level of rat cerebral enolase. AB - Gamma gamma (gamma gamma) enolase amount and enolase isozyme activities were measured in brain structures involved in stress response (hypothalamic paraventricular and supraoptic nuclei, locus coeruleus, hippocampus, A1 and A2 regions, hypophysis). Analyses were made in rats after immobilization or adrenalectomy, two experimental conditions that have been reported to increase brain glucose consumption and protein synthesis. In control rats enolase content was highest in the A1 region and hippocampus and lowest in hypophysis. A positive correlation was found between the enzyme level and its activity in the brain regions studied. However, in stressed or adrenalectomized rats, the level of glycolytic enzyme enolase was not significantly modified. PMID- 2097591 TI - Age-related changes in the subcortical afferents to the medial frontal cortex in mice: a WGA-HRP study. AB - The subcortical afferent projections to the mediodorsal part of the frontal cortex were studied both qualitatively and quantitatively in young (3 months), adult (12 months) and aged (22 months) Balb/c mice by means of the retrograde transport of wheat germ agglutinine-horseradish peroxidase (WGA-HRP). A progressive decrease in the number of afferents was observed during aging with a differential pattern of reduction as a function of the subcortical structures. In adult mice a large reduction of afferents occurs in the diagonal band of Broca, the posterior thalamic nucleus, the zona incerta, the lateral hypothalamic area, the nuclei of amygdaloid complex, the posterior hypothalamic nucleus, the reticular pontine nucleus, the dorsal and medial raphe nuclei and the dorsal tegmental nucleus. In aged animals, only the anteromedial and mediodorsal thalamic nuclei, as well as the locus coeruleus appear to be clearly affected. PMID- 2097592 TI - Some central effects of brofaromine given repeatedly are phase-dependent. AB - Effects of the MAO-A-inhibitor brofaromine (BRO), 10 mg/kg po after repeated (twice daily for 14 days) administration on the spontaneous behavior (exploratory and basal locomotor activities) and the exploratory activity modified by methoxamine, clonidine and d-amphetamine in male Wistar rats were studied in both light and dark phases of a diurnal cycle (L: 0700-1900 h). After single administration BRO in the light phase had no effects. In the dark phase BRO decreased the exploration (62% of control, p less than 0.01), increased the clonidine-evoked hypoactivity and amphetamine-evoked hyperactivity. The L-D differences occurred also after repeated administration. BRO in the light phase did not influence the exploration, decreased basal locomotor activity, did not change methoxamine and clonidine action and potentiated the action of amphetamine. In the dark phase, however, it did not influence the exploration and basal locomotor activity, intensified the methoxamine effect, and did not change the clonidine and amphetamine actions. The results demonstrate that the effects of BRO on behavior in rats: 1) differ from the effects caused by other antidepressants which are not MAO inhibitors; 2) are phase-dependent after both single and repeated administration. PMID- 2097593 TI - Shuttle-box avoidance facilitation by minaprine in mice. AB - The effects on shuttle-box avoidance acquisition of the new antidepressant minaprine (1, 2.5, 5 or 10 mg/kg) and of the classical antidepressant desipramine (0.5, 1, 2.5 or 5 mg/kg) were tested, without pretreatment or after a 5 day pretreatment, in mice of the CD-1 strain, subjected to five daily 100-trial training sessions. Minaprine, recently proposed as a new nootropic agent, facilitated avoidance performance when given to pretreated animals at a dose of 10 mg/kg, which had no effect on spontaneous locomotor activity. Desipramine did not exert any significant effect on avoidance responses. The results are in agreement with previous findings showing learning improvements by minaprine, but do not clarify the mechanism involved in the avoidance facilitation. PMID- 2097594 TI - The effect of ethanol and serotonin on blood vessels of the rat. AB - In in vitro conditions ethanol dose-dependently contracts the isolated tail artery and aorta of the rat. In concentration 0.03 M ethanol did not change the perfusing pressure in isolated vessels, but potentiated the contracting action of serotonin. In concentration of 0.1 M ethanol did not change the sensitivity of blood vessels to serotonin, and in concentration of 0.3 M inhibited it. Statistically significant changes were observed only in tail artery. The tail artery isolated from the rat receiving a single dose of ethanol (2 g/kg) displayed decreased sensitivity to action of serotonin. Chronic administration of ethanol (6 g/kg/day for 14 days) did not change the serotonin-induced contraction of the isolated tail artery of the rat. The present data indicate that ethanol modifies the sensitivity of rat blood vessels to serotonin. PMID- 2097595 TI - The effects of ethanol treatment on endogenous opioid peptides level and analgesia in monoarthritic rats. AB - The effect of acute and repeated exposure to ethanol on endogenous opioid peptides level in rats was studied. Acute ethanol administration decreased beta endorphin level in hypothalamus and anterior lobe of pituitary as well as alpha neoendorphin in the spinal cord. In contrast, repeated ethanol treatment increased hypothalamic beta-endorphin content and did not affect the peptide level in the pituitary. No changes in alpha-neoendorphin and dynorphin level after repeated ethanol administration were observed. Exposure of rats to long term noxious stimuli by means of induction of monoarthritis prevented the increase in hypothalamic beta-endorphin level by repeated ethanol treatment. As measured by tail-flick test only the first two administrations of ethanol resulted in analgesia. Further administration of increasing doses of ethanol did not affect the pain threshold. Altered response of endogenous opioid systems to repeated ethanol treatment as compared with effects of its acute administration may suggest involvement of these systems in development of tolerance to ethanol. PMID- 2097596 TI - Different calcium requirements during incorporation of myo-inositol into membrane lipids for phosphatidylinositol hydrolysis stimulated by carbachol and noradrenaline. AB - Stimulation of phosphatidylinositol hydrolysis by noradrenaline requires the presence of calcium in the medium during the whole incubation and preincubation procedure, while carbachol-induced inositol phosphate formation is equally efficient in calcium-free and calcium-containing medium. This finding confirms the notion that phosphatidylinositols mobilized after stimulation of various receptors are present in different metabolic pools: the pool mobilized by alpha 1 adrenoceptors is apparently formed from myo-inositol incorporated into membrane phospholipids by a calcium-dependent process. PMID- 2097597 TI - Erythrocyte membrane stabilization by calcium channel blockers, calmodulin antagonists and scavengers of oxygen free radicals. AB - Calcium channel blockers (nifedipine, verapamil, diltiazem), calmodulin antagonists (trifluoperazine, calmidazolium, compound 48/80) and anti-free radical agents (allopurinol, desferrioxamine, mannitol, L-methionine) were tested for their potency to stabilize human erythrocytes against hypotonic hemolysis. The anti-free radical agents and compound 48/80 did not confer the membrane stabilization. Nifedipine, verapamil, diltiazem, calmidazolium and trifluoperazine at low concentrations, protected the cells from the hypotonic hemolysis while at higher concentrations they caused lysis. Similar biphasic changes were produced by the detergents sodium dodecyl sulphate (SDS) and Triton X-100. The drug concentration-dependency of the biphasic changes in the erythrocytes osmotic fragility produced by calcium channel blockers and calmodulin antagonists was not affected by low concentrations of SDS and Triton X 100. On the other hand, these drugs did not prevent the hemolysis produced by high concentrations of the detergents. The above as well as the observation that the membrane stabilization is conferred only by relatively high concentrations of calcium channel blockers and calmodulin antagonists suggest that membrane stabilization is not responsible for anti-ischemic effects of these agents reported in the literature. PMID- 2097598 TI - Pharmacokinetics of mexiletine and its metabolites, hydroxymethylmexiletine and p hydroxymexiletine, after single oral administration in healthy subjects. AB - Pharmacokinetics of mexiletine and its major metabolites, p-hydroxymexiletine and hydroxymethylmexiletine, were studied in 10 healthy subjects after administration of a single oral 400 mg dose. Mexiletine was extensively metabolized to hydroxymethylmexiletine and less to p-hydroxymexiletine. Mean metabolic ratio (Rm) was 0.54 and 0.18 respectively. Peak serum concentrations (Cmax) for mexiletine (0.686 +/- 0.110 micrograms/ml), hydroxymethylmexiletine (0.507 +/- 0.087 micrograms/ml), and p-hydroxymexiletine (0.096 +/- 0.046 micrograms/ml) occurred after 3.0, 4.0 and 4.2 +/- 0.6 h. Disposition parameters for mexiletine were as follows: volume of distribution (V lambda), 5.44 +/- 1.44 l/kg; serum clearance (CL) 8.08 +/- 1.23 ml/min/kg. There were no significant differences in elimination half-life (t1/2) and mean residence time (MRT) for mexiletine and its metabolites. Double-peak phenomenon was observed for all the subjects on elimination phase of mexiletine, hydroxymethylmexiletine and p-hydroxymexiletine. PMID- 2097599 TI - Derivatives of (R,S)-1-N-(theophyllinyl-7'-ethyl)-amino-2-propanol with antiarrhythmic activity. AB - Three (R,S)-1-N-(theophyllinyl-7'-ethyl)-amino-2-propanol derivatives were obtained as soluble hydrochlorides and tested in four models of experimental arrhythmia. Two compounds 1a and 2 have shown antiarrhythmic properties and very low toxicity. PMID- 2097600 TI - [Surface antigens of male germ cells--their identification and functional analysis]. PMID- 2097601 TI - [Ethanol: current theories on its toxic effect with special reference to the effect on the central nervous system of adult mammals and during individual development]. AB - Present-day views on the molecular mechanism of ethanol action upon the central nervous system of adult mammals as well as consequences of the brain exposure to ethanol during fetal life, and upon the development and function of this organ in postnatal life are reviewed. Mechanisms of teratogenic effect of ethanol are also discussed. PMID- 2097602 TI - [Neurologic manifestations of chronic alcoholism]. AB - The authors have analyzed histories of 146 alcoholics admitted to the Clinic of Neurology. Results of this analysis and review of the literature became background for presentation of contemporary views on the clinic and neuropathology of chronic alcoholism. PMID- 2097603 TI - [Current theories on biotransformation and metabolism of mercury]. AB - The authors discuss problems connected with the natural occurrence, biotransformation and metabolism of mercury. The presented data indicate the methylation and demethylation of mercury both in the environment and in laboratory animals and in human subjects occupationally exposed and non-exposed to mercury in terms of absorption, distribution and elimination. PMID- 2097605 TI - [Von Willebrand factor]. AB - During the last decade a considerable amount of research has been dedicated to von Willebrand factor. In the first part of this article recent data on primary structure of von Willebrand factor and biosynthesis of von Willebrand factor multimers are presented. The second part focuses on the role of von Willebrand factor in hemostasis. PMID- 2097604 TI - [Immunochemistry of eukaryotic ribosomes]. AB - Immunochemical investigations of ribosomes should correlate with basic knowledge of the function, structure and activity of organelles in the cell processes. Our paper presents data of immunochemical methods used to determine the structure, function and differences of ribosomes. We present the usefulness of immunochemical methods to test human ribosomes, diagnosis and therapy of many diseases. PMID- 2097606 TI - [Structure and function of the outer membrane of Gram-negative bacteria]. PMID- 2097608 TI - [The role of leukocytes in hemostatic reactions]. PMID- 2097607 TI - [Interleukin 3--biochemical properties and biological activities]. PMID- 2097610 TI - [Structure and properties of neuraminidase originating from various sources]. AB - Glycoprotein such as neuraminidase is an enzyme occurring in some viruses and bacteria. It is characterized by a series of specific biochemical, enzymatic and immunological properties. The observed prevalence of chronic virus infections as well as liver diseases, glomerulonephritis, conjunctive tissue diseases and other autoaggressive illnesses which occur in their course have become the reason for experimental studies in which according to established patterns enzymatically active and inactive neuraminidase was administered to rabbits in a prolonged way. PMID- 2097609 TI - [Autoimmune thyroid diseases--cell mediated immunity]. AB - Some aspects of cellular immunity of autoimmune thyroid diseases are reviewed. Changes in number subpopulations and functions of T-lymphocytes in Graves' and Hashimoto's diseases with special attention to leucocyte migration inhibition test are described. Correlation between cellular and humoral immune factors is discussed. PMID- 2097611 TI - [Nephrotoxicity of aminoglycosides]. AB - The paper presents recent views on the aminoglycoside (AG) nephrotoxicity. The risk factors for nephrotoxicity in the patients treated with AG are discussed. PMID- 2097613 TI - [Mechanism of action and applications for glucose analogs]. AB - The paper presents recent problems of the mechanism of the action of glucose analogs (especially 2-deoxy-D-glucose and 5-thio-D-glucose) at the cellular level as well as their application in experimental and clinical medicine. It has been discussed, whether 2-DG and 5-TG could be assumed to represent nonmetabolizable antimetabolites of glucose. PMID- 2097612 TI - [Is chirality a key to stereoselective drug action?]. AB - The aim of this paper is to analyse examples of stereoselective binding of drugs to receptor sites. Selected examples are also given for the binding of drugs to serum albumin and for stereochemical aspects of drug metabolism. PMID- 2097614 TI - [Nitrates and nitrites in the environment and their effect on human health]. AB - The review was made on the major sources of human exposure to nitrates and nitrites, metabolism of these chemicals and their content in different body fluids. The health consequences of ingestion of nitrates and nitrites were presented. The methods of determination of nitrates, nitrites and nitrosamines were discussed. PMID- 2097615 TI - IV Inter-regional Meeting of the Liguria, Lombardia, Piemonte Valle d'Aosta Group of the Italian Pharmacological Society. Genoa, 2 February, 1990. PMID- 2097616 TI - Behavioural effects of A1/A2 adenosine-selective antagonists in the mouse. PMID- 2097618 TI - Effects of rubidium chloride and piracetam upon consolidation of memory in mice. PMID- 2097617 TI - Side effects of imipramine therapy in enuretic children. PMID- 2097619 TI - Influence of bestatin on feeding behavior. PMID- 2097620 TI - The effect of histidine on the cytotoxicity of hydrogen peroxide in cultured mammalian and bacterial cells. PMID- 2097621 TI - The inhibition of hepatic microsomal drug metabolism in rats by non-steroidal anti-inflammatory drugs. PMID- 2097622 TI - Effects of adenosine on the SA and AV nodes in different species. PMID- 2097623 TI - Frequency of stimulation affects ouabain-amiloride interaction in isolated atria: role of Na+/Ca2+ exchange. PMID- 2097624 TI - Effect of BBR 2160 on ICa recorded from guinea-pig isolated myocytes. PMID- 2097625 TI - Etozoline and vascular spasm. PMID- 2097626 TI - Gangliosides improve urinary bladder dysfunction in experimental diabetic autonomic neuropathy. PMID- 2097627 TI - Analysis of the effects of Ca++ modulating drugs on F10/B16 melanoma cells. PMID- 2097628 TI - Quantified EEG in different hypertensive rat strains and its modifications by oxiracetam (OXI). PMID- 2097629 TI - Biochemical and autoradiographic identification of prolactin binding sites in the rat hypothalamus. PMID- 2097630 TI - Behavioural effects of different calcitonins in rats. PMID- 2097631 TI - Effects of 17-beta-estradiol on the ontogenesis of striatal dopaminergic receptors. PMID- 2097632 TI - Importance of cholinergic pathways in the regulation of colonic motility in the rabbit. PMID- 2097633 TI - In vivo [3H]oxiracetam binding to rat brain. PMID- 2097634 TI - Absence of tumor initiating effect in the liver of rats treated with chlordiazepoxide plus sodium nitrite. PMID- 2097635 TI - Influence of chronic morphine treatment on dopaminergic sensitivity. PMID- 2097637 TI - V Inter-regional Meeting of the Basilicata, Calabria, Campania, Puglia, Sicilia, Sardegna Group of the Italian Pharmacological Society. Copanello (Catanzaro), 4-5 May, 1990. PMID- 2097636 TI - A dopaminergic mechanism mediates the d-amphetamine- and apomorphine-induced increase of ascorbic acid metabolism in the rat striatum. PMID- 2097638 TI - Analysis of immobilization stress-induced changes of ascorbic acid, noradrenaline, and dopamine metabolism in discrete brain areas of the rat. PMID- 2097639 TI - D1 receptors mediated vacuous chewing in the rat: a model of tardive dyskinesia. PMID- 2097640 TI - Effect of calcium antagonists on [3H]dopamine uptake. PMID- 2097641 TI - Conditioned place preference induced by ethanol in a rat line selected for ethanol preference. PMID- 2097642 TI - Correlations among receptor status, estrogen receptor (ER) form (8S and/or 4S) and labelling index (LI) in human breast cancer. PMID- 2097643 TI - Influence of pineal gland lesion on interleukin-2 production and natural killer activity in C57BL/6 mice. PMID- 2097644 TI - Interleukin-6 mediates neural-immune interactions: study on prolactin release and intracellular transducing mechanisms. PMID- 2097645 TI - Effect of chronic ethanol administration to adult or pregnant rats on phorbol ester binding in various brain areas. PMID- 2097646 TI - Effect of Vaccinium myrtillus anthocyanins on triiodothyronine transport into brain in the rat. PMID- 2097647 TI - Rat hypothalamic corticotropin-releasing hormone secretion is stimulated by interleukin-1 in an eicosanoid-dependent manner. PMID- 2097648 TI - Endothelin responses in bovine pulmonary arterial muscle preparations in vitro: modification by potassium ion alterations. PMID- 2097649 TI - Responsiveness and sensitivity to cholinergic agonists and antagonists in bovine isolated bronchial muscles. PMID- 2097650 TI - Influence of essential fatty acid deficient diet on some manifestations of endotoxin shock in rats. PMID- 2097651 TI - Release of EDRF from human umbilical vessels. PMID- 2097652 TI - Evidences for a role of tumor necrosis factor (TNF) in splanchnic artery occlusion shock in the rat. PMID- 2097653 TI - Diethylstilbestrol (DES) and recombinant human growth hormone (rhGH) as modulators of breast cancer proliferative activity. PMID- 2097654 TI - Nimodipine and phosphatidylcholine in clinical hemorheology. PMID- 2097655 TI - Electrophysiological and haemodynamic effects of some active principles of Harpagophytum procumbens DC. in the dog. PMID- 2097656 TI - Influence of fructose 1,6-diphosphate on the lung antioxidant defenses of mice with endotoxemia. PMID- 2097657 TI - A cytotoxic effect of H2O2 on Trichomonas vaginalis may be correlated to cytoskeleton modification. PMID- 2097658 TI - Research on heterocyclic compounds. Phenyl derivatives of fused imidazole systems: antiinflammatory activity. PMID- 2097661 TI - V Inter-regional Meeting of the Emilia-Romagna, Friuli-Venezia Giulia, Marche, Trentino-Alto Adiage, Veneto Group of the Italian Pharmacological Society. Trieste, 1 June, 1990. PMID- 2097660 TI - Effect of L-649, 923, an LTD4 antagonist, on phospholipase A2-induced hypotension. PMID- 2097659 TI - Research on heterocyclic compounds. Antiinflammatory activity of some imidazo(1,2 c)pyrimidine derivatives. PMID- 2097662 TI - In vitro cytostatic activity on new ruthenium complexes with heterocyclic dithiocarbamates. PMID- 2097663 TI - Exposure of an adriamycin-binding site on mast cell surface during exocytosis. PMID- 2097664 TI - Enhancement of antimicrobial drugs by normal rat serum and pleural carrageenan exudate. PMID- 2097665 TI - Genotoxic risk associated with pesticides: evidences on short-term tests. PMID- 2097667 TI - Adrenergic neuron blocking agents, psychological stress and tumor metastasis formation in mice. PMID- 2097668 TI - A possible role of proopiomelanocortin peptides in self-injurious behavior. AB - 1. The hypothesis that opioids may be involved in self-injurious behavior is supported by fifteen years of basic animal research suggesting that opioid peptides of the brain and spinal cord participate in the modulation of antinociception in animals, and research of animal models for self-injurious behavior utilizing exogenously administered opiate agonists. 2. Clinical biochemical and pharmacological research conducted over the past five years has also suggested the possibility that opioid peptides may play an important etiological role in the elaboration of self-injurious behavior in some individuals. 3. An opioid overactivity self-injurious hypothesis is supported by results of one study indicating elevated Fraction II opioids (enkephalins) in the lumbar-thecal cerebrospinal fluid of self-injurious children compared to controls, and by the five out of six published studies demonstrating statistically significant decreases in the frequency of self-injurious behavior with the opiate antagonist, naltrexone. 4. A very recent investigation has suggested that some self-injurious individuals show abnormalities in their plasma proopiomelanocortin peptide response to naltrexone, thereby indicating a possible dysfunction in the responsitivity of the proopiomelanocortin system of the hypothalamic-pituitary-adrenal axis of these individuals. 5. These data and results of other investigations have resulted in the elaboration of the original opioid hypothesis to a more comprehensive biochemical model that focuses on this proopiomelanocortin dysregulation. 6. Because of biochemical and functional interrelationships between proopiomelanocortin peptides and certain other neurochemical systems in the brain, it is proposed that pineal melatonin and serotonin may also be involved in this dysregulation. Further basic and clinical research will be needed to test the proposed biochemical model for self-injurious behavior. PMID- 2097666 TI - Reduction of MCa mammary carcinoma in mice fed with egg-white lysozyme. PMID- 2097670 TI - A review of pharmacological agents for self-injurious behavior. AB - 1. The clinical literature regarding the effects of various psychotropic agents on self-injurious behavior is reviewed. Anecdotal reports, open trials and controlled studies are each reviewed. 2. The absence of controlled studies and the failure to distinguish self-injurious behaviors from other forms of aggression are highlighted. 3. However, the review does raise the possibility that a wide range of agents may be useful for treating self-injurious behaviors and these appear to be similar to the agents used to treat other forms of aggression. PMID- 2097669 TI - The behavioral neurobiology of self-injurious behavior in rhesus monkeys. AB - 1. Self-injurious behavior (SIB) is prevalent among institutionalized children, but the efficacy of current behavioral and pharmacological treatments is marginal. 2. There is evidence that SIB in humans has a neurobiological basis. A better understanding of the neurobiological factors that may promote or cause SIB is necessary for the development of effective pharmacologic treatments. 3. SIB that is similar in some respects to SIB in humans occurs in nonhuman primates that have been deprived of social experience early in life. An analysis of the "cause" of SIB suggests that it is a relatively straight-forward example of the development of neurobiological and behavioral aspects of aggressive behavior in the absence of social factors that would normally bring the behavior under environmental control. Once induced, however, it becomes environmentally autonomous and its proximal cause is neurobiological in nature. 4. There are three lines of evidence that nonhuman primate SIB is linked to malfunctions in the norepinephrine (NE) and serotonin (5HT) neurotransmitter systems. The activity of these systems appears to be altered by psychosocial deprivation. The functional relationship between the two systems appears to be altered or absent in socially deprived monkeys. Pharmacologic agents that act on these systems alter SIB in monkeys. 5. Preliminary data from socially deprived rhesus monkeys are consistent in major respects with studies linking altered serotonin systems to self-injurious behavior and suicidal motivation in humans who also probably suffer from social deprivation. 6. Taken together, these findings indicate that developmental study of biogenic amine systems, particularly finding ways to circumvent deficits in, or restore functional linkages between, the 5HT and NE systems, will lead to a greater understanding of the neurobiologic basis of SIB in humans and animals and will enable us to develop more effective treatments of SIB. PMID- 2097671 TI - Neurochemical effects of chronic haloperidol and lithium assessed by brain microdialysis in rats. AB - 1. Psychotropic drugs ameliorate psychotic symptoms only after repeated administration. 2. To assess the neurochemical effects of chronic haloperidol and lithium administration, microdialysis was performed simultaneously in the prefrontal cortex, the nucleus accumbens, and the striatum after haloperidol, and separately in the lateral hypothalamus and the hippocampus after lithium. 3. Chronic administration of haloperidol decreased dopamine turnover in the prefrontal cortex and the striatum. It did not affect the nucleus accumbens detectably. 4. No tolerance to haloperidol developed in any of the three regions. 5. Lithium enhanced the response of the serotonergic system to amphetamine in the lateral hypothalamus but not in the hippocampus. 6. The antipsychotic effect of haloperidol might be related to dopamine turnover decrease in the prefrontal cortex. 7. The antidepressant effect of lithium might be related to enhancement of serotonin responsiveness in the hypothalamus. PMID- 2097672 TI - In vivo measures of monoamines during amphetamine-induced behaviors in rats. AB - 1. Using a removable in vivo microdialysis probe, and remote sample collection, the temporal and dose-related behavioral and monoamine response to amphetamine (AMPH) were examined in freely-moving rats. Extracellular dopamine, serotonin and their metabolites were monitored concomitant with detailed characterization of the locomotor and stereotypy profiles. Consistent with previous results, AMPH (0.5-5.0 mg/kg) induced a rapid dose-dependent increase in dopamine concentration and decrease in the concentrations of the dopamine metabolites. Dopamine and metabolites exhibited contrasting temporal and dose-related patterns, suggesting that the decline in dopamine metabolites is functionally dissociated from the AMPH-enhanced dopamine release, and that metabolite levels do not provide an accurate index of functional dopaminergic activity. 2. Dose response comparisons revealed a significant relationship between AMPH-induced increases in behavioral perseveration and the magnitude and duration of the dopamine release. However, the temporal patterns of the neurotransmitter response and individual components of stereotypy were not parallel, suggesting that the presence of stereotypies is not associated simply with quantitative differences in striatal dopamine release. 3. Consistent with this interpretation, we found that a variety of manipulations including reserpine, apomorphine, and chronic amphetamine pretreatment, produced a dissociation between the alterations in the behavioral and dopaminergic responses to amphetamine. The behavioral response to amphetamine may be influenced by the interaction between levels of dopamine and serotonin, by the state of their respective receptors, and by the relative contributions of additional dopaminergic systems. PMID- 2097673 TI - Microdialysis as an approach to quantitate the release of neuropeptides. AB - 1. In vivo microdialysis was performed on anesthetized and awake rats to measured release of cholecystokinin from the posterior nucleus accumbens. 2. Basal levels of cholecystokinin were detectable by radioimmunoassay in some, but not all animals. 3. Recovery through the microdialysis probe ranged from 0.1-2.4% for cholecystokinin, suggesting practical limitations to this approach with present technology. PMID- 2097674 TI - Utilization of microdialysis for assessing the release of mesotelencephalic dopamine following clozapine and other antipsychotic drugs. AB - 1. In vivo microdialysis was utilized to assess the effect of clozapine, haloperidol, and sulpiride on the release of dopamine from the nucleus accumbens, striatum, and prefrontal cortex of the rat. 2. The results suggest that acute administration of various classes of antipsychotic drugs may differentially increase the extracellular concentration of dopamine in mesotelencephalic systems. Haloperidol and sulpiride were more effective in releasing dopamine from the terminals of the nigrostriatal dopamine system while clozapine had a more prefrontal effect on the mesolimbic and particularly the mesocortical dopamine systems. PMID- 2097675 TI - Self-injurious behavior. Introduction. PMID- 2097676 TI - Passing rates of American children and youth on the FITNESSGRAM criterion referenced physical fitness standards. AB - The purpose of this study was twofold: (1) to determine the percentage of 6-18 year-old students who passed the FITNESSGRAM criterion scores for percent body fat (%BF), body mass index (BMI), mile run (MR), sit-ups (SU), pull-ups (PU), and sit and reach (S&R), and (2) to suggest and illustrate the instructed uninstructed/mastery-nonmastery technique for the validation of criterion referenced cut-off scores. The data base consisted of the NCYFS I and II national probability samples of students. Results showed that the most frequently passed item was the S&R (M = 90%; F = 97%), followed by the two body composition items (%BF: M = 89%; F = 91%) (BMI: M = 88%; F = 85%), the MR (M = 77%; F = 60%), SU (M = 65%, F = 57%), and finally the PU (M = 73%; F = 32%). It is recommended that the criterion cut-off scores be statistically validated using the illustrated technique when the active (instructed) group has been trained with documented levels of frequency, intensity, and duration and the inactive (uninstructed) group is truly sedentary. PMID- 2097677 TI - Cardiorespiratory and perceptual responses to arm crank and wheelchair exercise using various handrims in male paraplegics. AB - The purpose of the present study was to determine the effects of 10-in [0.25-m] versus 16-in [0.41-m] wheelchair handrims on cardiorespiratory and psychophysiological exercise responses during wheelchair propulsion at selected velocities. Fifteen male paraplegics (27.0 +/- 5.5 yrs) performed three discontinuous exercise tests (ACE = arm crank ergometer; WERG = wheelchair roller ergometer) and two 1600-m performance-based track trials (TRACK) under simulated race conditions. There were no significant differences in HR, VO2, VE, HLa, or category-ratio ratings of perceived exertion (RPE) using different handrims during wheelchair propulsion at 4 km.h-1. In contrast, at 8 km.h-1 subjects demonstrated a 13% lower steady state VO2 (p less than .05) using the 10-in handrims, coincident with a 23% lower VE. Steady state HR during WERG at 8 km.h-1 using the 10-in (124.4 +/- 3.9 b.min-1) or 16-in (130.6 +/- 4.6 b.min-1) handrims were not significantly different. There were also no significant differences between ACE or WERG conditions during maximal effort for VO2 or VE. However, HRpeak during ACE was 7% higher than HRpeak during WERG16 (183 +/- 15 b.min-1 vs. 171 +/- 12 b.min-1, p less than .05), and whole blood HLa during ACE was also significantly higher (by 2.3-2.5 mmol; p less than .05) compared to WERG. There were no significant differences for HR, performance time, or RPE between trials using different handrim diameters during the 1600-m event.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097678 TI - An analysis of the validity of the three-mile run as a field test of aerobic capacity in college males. AB - The purpose of the present investigation was to examine the concurrent and construct validity of the three-mile (4.83 km) run as a field test of aerobic capacity. Subjects included 109 college-aged males whose three-mile run time (M = 1310.31 +/- 184.48 s) was measured. Fifty of the subjects were given a maximal treadmill stress test, and their peak oxygen consumption (VO2peak) (M = 54.23 +/- 7.08 ml.kg-1.min-1) was measured. The three-mile run was conducted on an outdoor 0.25 mile (0.425 km) track, and split times were recorded each 110 yds (100.32 m) for the first and last laps and total time was recorded for laps 2 through 11. The correlation coefficient between the run time and VO2peak was -.58, indicating only moderate concurrent validity for the run as a field test for aerobic capacity. A factor analysis conducted on the split time data revealed a three factor structure of a stable pace phase, an initial sprint, and a final sprint with the stable pace factor accounting for most of the common factor variance (69%). The three-mile run time was used to discriminate successfully between two known groups of subjects in aerobic capacity. These data provide a degree of support for the construct validity of the three-mile run as a field test of aerobic capacity. PMID- 2097680 TI - Effects of exercise on bone mineral content in postmenopausal women. AB - The purpose of this study was to test the effects of a 10-month exercise program on bone mineral content (BMC) and bone mineral content/bone width (BMC/BW) of postmenopausal women. Thirty-one women (ages 57-83) completed either a general aerobics exercise program (n = 10), a general aerobics plus upper body weight training exercise program (n = 10), or served as nonexercising control subjects (n = 11). Average compliance rates for the exercise subjects ranged from 72 to 80%. All subjects were pre- and posttested for BMC and BMC/BW in the radius of the nondominant forearm. ANOVA results indicated that there were significant differences between the exercise and control subjects in the amount of change in BMC and in BMC/BW (p less than .05) during the course of the study. The exercise subjects experienced mean increases of 1.38% and 1.33% in BMC and BMC/BW, respectively, whereas the control group had decreases of 2.50% and 2.58%. No significant differences were found for subjects in the two types of exercise programs, suggesting that the effects of exercise relative to maintenance of bone density may be general as well as localized. PMID- 2097679 TI - Sex differences in static strength and fatigability in three different muscle groups. AB - Maximal voluntary static muscle force production was assessed both in strength trials and during 2-min contractions by three muscle groups (right-hand finger flexors [RHF], right-leg extensors [RLE], and both leg extensors [BLE]) in young males (n = 13) and females (n = 14). There was a significant difference (p less than .01) between males and females for RHF strength and BLE strength but no significant difference between sexes for RLE strength. During the 2-min task, impulse (force x time) declined significantly (p less than .001) and there was a significant difference (p less than .001) between muscle groups, but there was no difference between sexes. There was a significant (p less than .05) sex x time interaction for the impulse values indicating that the fatigability was greater in males than females. PMID- 2097681 TI - The relation between children's accuracy estimates of their physical competence and achievement-related characteristics. AB - The relationship between perceptions of competence and control, achievement, and motivated behavior in youth sport has been a topic of considerable interest. The purpose of this study was to examine whether children who are under-, accurate, or overestimators of their physical competence differ in their achievement characteristics. Children (N = 133), 8 to 13 years of age, who were attending a summer sport program, completed a series of questionnaires designed to assess perceptions of competence and control, motivational orientation, and competitive trait anxiety. Measures of physical competence were obtained by teachers' ratings that paralleled the children's measure of perceived competence. Perceived competence and teachers' ratings were standardized by grade level, and an accuracy score was computed from the difference between these scores. Children were then categorized as underestimators, accurate raters, or overestimators according to upper and lower quartiles of this distribution. A 2 x 2 x 3 (age level by gender by accuracy) MANCOVA revealed a significant gender by accuracy interaction. Underestimating girls were lower in challenge motivation, higher in trait anxiety, and more external in their control perceptions than accurate or overestimators. Underestimating boys were higher in perceived unknown control than accurate and overestimating boys. It was concluded that children who seriously underestimate their perceived competence may be likely candidates for discontinuation of sport activities or low levels of physical achievement. PMID- 2097682 TI - Sex bias and the validity of believed differences between male and female interscholastic athletic coaches. AB - Previous research indicates that young athletes as well as athletic administrators hold gender-role stereotypical beliefs about coaches that disfavor females. The validity of two such beliefs (lack of qualified female coaches and time constraints due to family responsibilities) was examined in a statewide survey of 256 female and 296 male interscholastic coaches and a nationwide survey of 2,719 male and 1,449 female interscholastic coaches. Statistical analyses (p less than .001) indicated that female coaches were (a) more qualified than their male counterparts with respect to coaching experience with female teams, professional training, and professional experience; (b) as qualified as male coaches with regard to intercollegiate playing experience; and (c) less qualified than male coaches with respect to high school playing experience and coaching experience with male teams. Findings also indicated that male rather than female coaches more often experienced time constraints due to family responsibilities. PMID- 2097683 TI - Validation of a procedure to induce pain of varied intensities. PMID- 2097684 TI - An analysis of the NCYFS II Modified Pull-up Test. AB - The findings of this study are summarized as follows: 1. To obtain a reliable pull-up score for male subjects, it is necessary to administer the test on two days and use the mean of the two scores. For female subjects, a reliable score may be obtained by administering the test once. 2. The test scores are weight dependent for both sexes, but particularly for the older females. 3. The test is far superior to the pull-up and flexed-arm hang tests in regard to the zero-score problem. Zero scores are virtually eliminated with the modified pull-up test. In conclusion, the NCYFS II Modified Pull-up Test has two weaknesses--reliability for male subjects and weight dependency. The test, however, seems to be less weight dependent than the pull-ups or flexed-arm hang tests and virtually eliminates the zero-score problem. It therefore seems to be the most desirable of the tests of upper body strength currently in use. Further research regarding the validity of the test is recommended. PMID- 2097685 TI - Testing for hypothesized equality. PMID- 2097687 TI - Precision of knowledge of results: consideration of the accuracy requirements imposed by the task. PMID- 2097686 TI - A further analysis of the 12-minute run prediction of maximal aerobic power. PMID- 2097688 TI - The context of measurement instruction in physical education. PMID- 2097690 TI - [Erosion of tooth substance]. PMID- 2097689 TI - Gender-role orientations of male and female coaches of a masculine-typed sport. PMID- 2097691 TI - [Evaluation of effects of working conditions on quality of performance of dental health care workers in a health care center]. PMID- 2097692 TI - [Dental anxiety expressed in drawings by children]. PMID- 2097693 TI - [Use of sweeteners in medication]. PMID- 2097694 TI - [Reinforcement of prosthetic materials]. PMID- 2097695 TI - [Evaluation of reasons given for broken appointments by young adults]. PMID- 2097696 TI - [Critique by heads of dental departments in health care centers on the orientation of new dental graduates]. PMID- 2097698 TI - [International cooperation in the field of periodontics]. PMID- 2097699 TI - Paradoxical effects of antibiotics. AB - The paradoxical effect of antibiotics is defined as a substantially reduced bacterial killing at antibiotic levels above the minimal bactericidal concentration in vitro. This phenomenon which was originally described for beta lactam antibiotics in their reactions against Gram-positive bacteria has later been noted with aminoglycosides against Gram-negatives and other antibiotic microorganism combinations, indicating a multifaceted background. The clinical significance of the paradoxical effect is unknown. However, the phenomenon can be demonstrated in vitro at levels easily achievable in clinical situations, as illustrated in our own experiments, where clinical isolates of Staphylococcus aureus were tested for a paradoxical effect versus several penicillins. In most strains exhibiting a paradoxical effect, this effect occurred at concentrations as low as 10xMIC. The relationship between paradoxical effect and tolerance is discussed. PMID- 2097697 TI - [University education in periodontics from 1950 to 1990. A perspective of the future]. PMID- 2097700 TI - Metabolic and ultrastructural effects induced by ciprofloxacin in Staphylococcus aureus during the postantibiotic effect (PAE) phase. AB - The new quinolone antibacterial agents have been found to produce a postantibiotic effect (PAE) of 1-4 h in bacteria but the underlying mechanism is still unknown. After exposure to ciprofloxacin in concentrations of 1-16 x MIC for 1 hr the DNA synthesis in S. aureus ATCC 25923 was investigated during the PAE. Ultrastructure was also investigated by electron microscopy after exposure to a concentration of 2 x MIC. The rate of DNA synthesis per organism (measured as CPM/cfu/ml) increased progressively up to a maximum value at 1 1/2 h after drug removal. The maximal 3H-thymidine incorporation per organism at this moment correlated directly with the duration of the PAE. Bacterial swelling with scarcity and vacuole-formation of the cytoplasm characterized the majority of the staphylococci during the PAE. The physiological importance of the increased DNA synthesis is unknown, but the increased metabolic activity, coincident with increased duration of the PAE, suggests a possible common mechanism. PMID- 2097701 TI - Prediction of antibiotic dosing intervals from in vitro susceptibility, pharmacokinetics and post-antibiotic effect: theoretical considerations. AB - Because of the complexity of determining minimum inhibitory concentration (MIC) values on multiple drugs in routine laboratories, susceptibility testing has been designed to generate 2 or 3 broadly-predictive susceptibility categories: susceptible, (intermediate), and resistant. In contrast, recent dosing studies in vivo have shown that for some antibiotics optimum efficacy is best predicted by time above the known MIC and any postantibiotic effect (PAE). It is possible that the optimum dosing interval can be approximated by the sum of the time greater than MIC and the duration of PAE. PAE is known to be related to AUC of drug concentration and time of exposure. Formulae are presented that should make it possible to calculate the optimum dosing interval mathematically by knowing (i) the drug's pharmacological parameters and dose, (ii) the organism's MIC and (iii) the relationship between AUC and PAE for the drug-organism combination. Both (i) and (iii) are predetermined values obtained from studies. For some bacterial species, isolates in the susceptible range have very similar MICs (narrow range) and the MIC is therefore reasonably predictable. However, for other species, the precise MIC needs to be measured to perform the calculations. Examples of the application of these formulae are given. PMID- 2097702 TI - Impact of the antibiotic dosage schedule on efficacy in experimental soft tissue infections. AB - Soft tissue infection models have been used to study both the postantibiotic effect (PAE) and the effect of dosage intervals on antimicrobial efficacy. In vitro findings were mostly confirmed. For drug-organism combinations which showed a predominantly time-dependent killing pattern and absence of a PAE (beta-lactams vs Gram-negative organisms), frequent drug dosing was most efficacious. In contrast, a fast, predominantly concentration-dependent bactericidal effect followed by a PAE in vitro (e.g. aminoglycosides vs Gram-negative bacteria) correlated (though inconsistently) with superiority of bolus dosing over more continuous drug administration in vivo. Thus, the ratio of peak serum concentrations to MICs of target pathogens is possibly a valid predictor of efficacy for the aminoglycosides but not so for the activity of beta-lactam antibiotics where the duration of coverage at supra-MIC levels was clearly more important than the magnitude by which initial peaks exceeded the MIC of the target organism. It is not clear to what extent the results obtained in experimental soft tissue infections may hold true in man. Thus far, only a limited number of drug-organism combinations have been studied in well defined experimental settings using mostly small, granulocytopenic animals which differ pharmacokinetically from man. In addition, results are probably affected by the density of bacteria, their growth rate and metabolic activity, but also by the extent of inflammation at the site of infection. PMID- 2097703 TI - Antibiotic uptake and transport by bacteria. AB - A few antibiotics, e.g. polymyxins, disorganize the bacterial wall. For most, however, the wall is an obstacle to be crossed. The extent of this barrier varies with the target to be reached, the drug and the bacterial species. Staphylococci and streptococci have only capsular material and peptidoglycan external to the cytoplasmic membrane (CM). These components afford little shielding and agents with targets on the outer surface of the CM (e.g. vancomycin and beta-lactams) have unhindered target access. Antibiotics with cytoplasmic or ribosomal targets must however cross the CM, usually by active transport. Mycobacteria have outer barriers beyond the CM, as do Gram-negative species. The latter organisms have an outer membrane (OM) located externally to the peptidoglycan and CM. Being hydrophilic, most antibiotics cross the OM by passive diffusion through pores composed of 'porin' proteins. Uptake varies with the drug's charge, size and hydrophilicity, also with the number of pores. Antibiotics larger than 800 D are excluded. Once across the OM, the antibiotics have access to the CM, which must be crossed by those with ribosomal or cytoplasmic targets. Resistance can arise by porin loss, or by loss of an active uptake pathway in the CM. Often the barrier is not absolute: rather uptake is reduced relative to drug removal or detoxification. Occasionally, e.g. with tetracyclines, resistance entails drug excretion or 'coating' of the ribosome. PMID- 2097704 TI - Impact of the antibiotic dosage schedule on efficacy in experimental lung infections. AB - In agreement with results obtained in the thigh infection model for which there is no human equivalent, the impact of the dosage schedule on efficacy in various clinically relevant experimental lung infections is related to the class of antibiotic. The efficacy of beta-lactams increases with increasing frequency of administration. Sustained antibiotic concentrations in serum at a relatively low level are more effective than high peak concentrations at intervals. In contrast, the dosing interval has little impact on the activity of aminoglycosides, which is mainly dependent on the total amount of antibiotic in serum during treatment, either as short lasting high peaks or as long lasting relatively low concentrations. Limited data available on quinolones suggest a slight increase in efficacy with increasing dosing intervals. These differences in efficacy correlate with differences in the pharmacodynamics of antibiotics of different classes as seen in vitro as well as in the lungs of infected animals. Knowledge about both the pharmacokinetics and pharmacodynamics of antibiotics is required for the correct interpretation of comparative studies on antibiotic efficacy in experimental infections, and also for the evaluation of experimental data as support for the proper design of clinical trials. PMID- 2097705 TI - Impact of the antibiotic dosage schedule on efficacy in experimental endocarditis. AB - The animal model of endocarditis provides a reliable and reproducible model of acute infection and appears appropriate for studying the parameters involved in the in vivo efficacy of antibiotic therapy. The following points are discussed: (i) beta-lactam antibiotics exhibit a time-dependent bactericidal effect which explains the importance of t1/2 beta in the determination of dosing intervals and the need for large unitary doses for increasing efficacy through extending the period of serum levels greater than MIC (ii). The impact of unitary doses and dosing intervals of aminoglycosides on their in vivo synergism with beta-lactams has been investigated in Escherichia coli and streptococcal infections. Once- daily dosing of netilmicin appears very synergistic with ceftriaxone on E. coli, and the aminoglycoside has a significant dose effect. Conversely, divided doses are necessary to exhibit full synergistic effect with penicillin G on E. faecalis. Different patterns of in vivo synergism can therefore be individualized (iii). The rapid bactericidal effect of quinolones and their in vivo post antibiotic effect allowing large intervals between doses have been investigated with ciprofloxacin (iv). The importance of t1/2 beta on the in vivo effect of glycopeptides is illustrated by data comparing teicoplanin and vancomycin. It is concluded that in vitro killing rate within 3 h is the major factor interfering with the dose interval, followed by t1/2 beta which is of major importance for those drugs whose bactericidal effect is time-dependent. These parameters appear to have a similar importance in experimental endocarditis to that in other experimental models. However, infected vegetations represent a particular focus of infection incorporating heterogeneity of antibiotic distribution, high density of bacteria and reduced metabolic activity of microorganisms. These factors may explain the lack of in vivo postantibiotic effect observed with some antibiotics, correspondingly shorter dosage intervals in endocarditis than in other types of infections and a need for high unitary doses. PMID- 2097706 TI - Pharmacodynamics of antibiotics in experimental bacterial meningitis--two sides to rapid bacterial killing in the cerebrospinal fluid. AB - In bacterial meningitis, several pharmacodynamic factors determine therapeutic success--when defined as sterilization of the cerebrospinal fluid (CSF); (i) local host defense deficits require the use of bactericidal antibiotics; (ii) CSF antibiotic concentrations that are at least 10-fold above the MBC are necessary for maximal bactericidal activity; (iii) high CSF peak concentrations that lead to rapid bacterial killing appear more important than prolonged suprainhibitory concentrations, probably because very low residual levels in the CSF prevent bacterial regrowth even during relatively long dosing intervals; (iv) penetration of antibiotics into the CSF is significantly impaired by the blood-brain barrier, thus requiring high serum levels to achieve the CSF concentrations necessary for rapid bacterial killing. Beyond these principles, recent data suggest that rapid lytic killing of bacteria in the CSF may have harmful effects on the brain because of the release of biologically active bacterial products. The conflict between the need for rapid CSF sterilization and the harmful consequences of bacterial lysis must be addressed in the therapy of meningitis. PMID- 2097707 TI - In vivo efficacy of cefcanel daloxate in comparison with cefaclor. AB - Cefcanel daloxate is a new prodrug cephalosporin for oral use, with cefcanel as the antibacterially active principle. The in vivo efficacy of this prodrug in comparison with cefaclor was assessed in a localized thigh infection model in mice. Mice were infected intramuscularly in the thigh and treated orally with cefcanel daloxate or cefaclor with three doses given 70 min apart. One strain each of S. aureus, Escherichia coli and Klebsiella pneumoniae was used as test organism. The first dose was given 60 min after staphylococcal infection or 15 min after infection with the Gram-negative strains. The doses given were 0.1 or 0.5 mmol/kg body weight, respectively. The animals were killed at predetermined times, the thigh was excised and homogenized and a count of viable bacteria was made. Decrease in bacterial numbers was used as a measure of the efficacy. The plasma and muscle concentrations of the two investigated drugs were also determined. Both drugs caused a reduction in viable count by approx. 90% for all test organisms, while in the untreated animals the number of bacteria increased 4 to 10 times within 6 hours after challenge. The plasma and tissue peak levels of cefcanel following administration of the daloxate were lower than those for cefaclor but cefcanel displayed a longer half-life. PMID- 2097708 TI - The postantibiotic effect of cefcanel on beta-hemolytic streptococci group A in vitro and in vivo. AB - The postantibiotic effect (PAE) of cefcanel, a new oral cephalosporin with high in vitro activity against Gram-positive bacteria, was investigated. Ten clinical isolates of Streptococcus pyogenes group A and one reference strain (M12, P1800) were exposed to 5 X MIC of cefcanel for 2 h in vitro. The PAE was found to be 2.3 (range 1.7-3.2) h. To investigate the PAE in vivo, a newly developed animal model with implanted tissue cages in rabbits was used. The rabbits received different doses of cefcanel i.v. and unbound concentrations in the tissue cage fluid (TCF) were measured. The protein binding of cefcanel in TCF was approximately 98%. Above a certain dose level, unexpectedly high TCF concentrations were found, indicating that the albumin binding capacity for the drug was surpassed. A PAE in vivo of 0.9-2.6 h was confirmed for cefcanel when the free drug concentration in TCF exceeded 3 X MIC. PMID- 2097709 TI - Intracellular pharmacokinetics and localization of antibiotics as predictors of their efficacy against intraphagocytic infections. AB - To be effective against intracellular bacteria, antibiotics must not only reach and preferably be retained in the infected subcellular compartments, but also be able to express their activity therein. beta-lactams are most often ineffective because they fail to concentrate in phagocytes. Aminoglycosides are taken up at a very slow rate and localize almost exclusively in lysosomes where their activity is largely defeated by the acid pH. Lincosamides and macrolides accumulate rapidly by phagocytes, and distribute both in lysosomes and in cytosol. Yet, most surprisingly, macrolides are active, whereas lincosamides are not, or only weakly active against sensitive organisms. Fluoroquinolones are also accumulated by phagocytes, but are not associated with a specific organelle. They show good activity against most sensitive organisms. A model of Staphylococcus aureus infected macrophages is presented to determine the intrinsic intracellular activity of antibiotics, i.e. to distinguish the influence of drug uptake from the other factors that modulate drug activity such as drug disposition and inactivation. This approach confirms the superiority of the fluoroquinolones as compared to presently available macrolides or to lincosamides. Thus, analysis of the pharmacokinetic and pharmacodynamic behavior of antibiotics in appropriate models of infected cells may help in directing future research towards improved derivatives, and may rationalize their use in vivo. PMID- 2097710 TI - Correlation of pharmacokinetic parameters to efficacy of antibiotics: relationships between serum concentrations, MIC values, and bacterial eradication in patients with gram-negative pneumonia. AB - In vitro, antibiotics are known to kill bacteria in predictable relationships to their broth concentrations. It was our hypothesis that serum concentration was an important determinant of the rate of bacterial eradication in patients. This contention was reinforced by animal studies, which have clearly demonstrated concentration-related antibacterial activity. The animal models rely on reduction of bacterial colony counts as an endpoint of effect, and demonstrate that colony count reductions are related to antibiotic dose and probably to serum concentration. We adapted these methods for use in intubated patients with Gram negative pneumonia. Briefly, each patient had extensive staging of the pneumonic process, and the Gram-negative organism was isolated and its minimal inhibitory concentration (MIC) was determined. In each patient measurement of the antibiotic serum concentrations in the interval between two doses of the drug was also performed. The pharmacokinetic profile of the drug was then superimposed on the bacterial MIC, and we then derived the patients individual peak to MIC ratio, area above MIC, and time above MIC. Each of these pharmacokinetic parameters was then related to the time required to eradicate the bacterial pathogens in the patient. For beta-lactams and quinolones, time above MIC was the most predictive of bacterial eradication times. Clearly, these methods can be used to develop dosing strategies for patients, as well as to determine clinically relevant doses and dosing strategies in clinical trials. Further work is needed, however, to assess whether these concepts hold for other types of bacteria (such as Gram positive) or apply as accurately to other infection sites in addition to pneumonia. PMID- 2097711 TI - Pharmacokinetics of antibiotics in tissues and tissue fluids: a review. AB - The majority of bacterial infections occur outside the vascular compartment and, thus, considerable interest has been devoted to studies of antibiotic concentrations in different tissues. This review deals with the pharmacokinetics of antibiotics in tissues where the drug is distributed by passive diffusion. It is not always recognized that tissue levels of antibiotics represent the means of different concentrations in the major tissue compartments: interstitial fluid, cells and blood capillaries. Non-lipophilic drugs, such as beta-lactam antibiotics, which do not penetrate cells, are confined to the extracellular fluid volume, which constitutes approximately 20% of the tissue. Consequently, whole tissue levels are low. Conversely, drugs that penetrate and accumulate in cells may well yield tissue levels exceeding the serum levels. Since most bacterial infections start and progress in the interstitial fluid, whole tissue levels are therapeutically meaningless, but are nevertheless often compared to the MICs of bacteria. For protein-bound drugs, the lower albumin concentrations in extracellular fluids is another important factor that may lead to erroneous conclusions regarding the ability of an antibiotic to distribute into tissues. Different models have been developed to study antibiotic levels in the interstitial fluid. The geometry of the tissue fluid compartment (ratio of surface area to volume: SA/V) has been recognized as one of the most important determinants of antibiotic pharmacokinetics in these models. In healthy tissues (high SA/V) similar concentrations are found in serum and tissue fluid. Although limited information is available regarding antibiotic pharmacokinetics in infected tissues, it seems that in acute bacterial infections, the most relevant concentrations to relate to pharmacodynamic parameters are the unbound levels of the drug in serum. PMID- 2097712 TI - Human pharmacodynamics of beta-lactams, aminoglycosides and their combination. AB - In-vitro and animal model data indicate that the time beta-lactam serum concentrations remain above the MIC is an important determinant of the organism kill at the primary infection site. Similarly, for aminoglycosides, area under the curve and peak concentrations have been linked to organism kill and suppression of resistance. It is only in clinical patients that these data can be validated as to their significance. For beta-lactams, little clinical data exist regarding these concepts. However, Bodey & colleagues have shown that profoundly, persistently neutropenic cancer patients fared better when one of their beta lactams was administered continuously. Our group was able to correctly predict outcome in 9/10 patients bacteremic with a Gram-negative bacillus when receiving a single beta-lactam on the basis of the time free drug concentrations remained above the MIC. Schentag et al studied patients with lower respiratory tract infection treated with cefmenoxime alone and found a significant relationship between time greater than MIC & time to clearance of the pathogen from cultures of the tracheobronchial tree. These data would seem to validate the predictive nature of the findings from in-vitro & animal model studies. With aminoglycosides, Moore, Smith & Lietman were able to demonstrate a highly significant correlation between outcome and the maximal peak concentrations to MIC ratio achieved for patients with single organism Gram-negative rod infections. This is somewhat at variance with some animal models, but as the studies were performed with a fixed dosing interval, the outcome is not surprising. Little has been done with combinations of these agents in patients. Barriere & colleagues have proposed the AUC of the reciprocal serum bactericidal activity curve as a way to integrate the activity of combinations. We have developed a method employing logistic regression analysis to integrate the activity from the administration of multiple agents. The integration of this approach with each drug's pharmacokinetics allows the generation of a plot of the probability of the blood remaining sterile over a steady state dosing interval. This approach has been preliminarily tested in 6 individuals with excellent concordance between outcome and prediction. Development of data in-vitro and in animal models with validation in patients will hopefully provide the impetus to optimize therapy, and thence, outcome for the most seriously ill individuals. PMID- 2097713 TI - Efficacy and safety of aminoglycosides once-a-day: experimental and clinical data. AB - In vitro and animal data show that the efficacy of an aminoglycoside is primarily related to its serum peak levels and AUC, whereas its toxicity is critically dependent upon the schedule of the administration of the daily dose as well as the duration of the treatment and the total amount of drug administered. The reduction of toxicity by intermittent dosing, e.g. once-a-day dosing (q.d.) versus splitting the daily dose in multiple administrations is connected with the saturable character of the aminoglycoside transport within inner ear and renal tissues. Clinical trials have been conducted in various types of infections in order to investigate the efficacy and tolerance of aminoglycosides q.d. Using conventional criteria of evaluation, this mode of administration was found to be equally efficacious and marginally less toxic than aminoglycosides in conventional dosing regimens. We have studied the pharmacokinetics and the early signs of renal (phospolipiduria) and auditory (high frequency audiometry) alterations of aminoglycosides given q.d. and by conventional dosage schedules to patients with pelvic inflammatory disease. It was shown that netilmicin and amikacin were better tolerated q.d. than after t.i.d. or b.i.d. administration. In addition, amikacin induced less alterations than netilmicin. PMID- 2097714 TI - Efficacy and safety of antibiotic treatment in relation to treatment time. AB - Decisions on treatment times with antibiotics are often arbitrary and based on empirical decisions or clinical trials which are too small to exclude even considerable differences between two study groups. Single-dose treatment of uncomplicated cystitis in women has been advocated by many but a careful analysis of available information clearly shows that a single-dose has so far always been inferior to 3-day or greater than 5-day treatment. With trimethoprim-sulphonamide combinations, no further efficacy is gained by increasing the treatment time in uncomplicated cystitis above three days while frequency of side effects increases drastically with extended treatment. In contrast, treatment with beta-lactams, for less than five days seems to result in unacceptable failure rates. In pyelonephritis there are few studies of the efficacy of antibiotic treatment for less than ten days. A comparison of two and six weeks' treatment showed no advantages with the extended time. There has also been a tendency towards reduced treatment times in upper respiratory tract infections such as streptococcal pharyngotonsillitis. However, two studies comparing 10-day treatment to 7-day and 5-day treatments, respectively, have clearly shown that the shorter treatment times give much higher rates of both clinical and bacteriological relapse. In more severe infections such as meningitis, no studies comparing treatment times have been carried out. It seems possible to use treatment for five days or less in meningococcal meningitis while other pathogens should be treated for ten days or longer. In endocarditis, the treatment time must vary with causative pathogens and can only rarely be shorter than four weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097715 TI - Pharmacodynamics of cefepime. AB - The microbiological activity of cefepime was assessed in vitro against 232 clinical isolates coupled with a pharmacokinetic evaluation at steady state in six patients receiving 1 g every 12 h. MIC90s were less than or equal to 0.25 mg/l for Enterobacteriaceae and streptococci. 1 mg/l for Staphylococcus aureus and 8 mg/l for Pseudomonas aeruginosa. Mean serum concentrations in patients were 62.5 +/- 2.7 mg/l (end infusion) and 1.1 +/- 0.8 mg/l (at 12 h) with an elimination half-life 2.72 +/- 0.59 h. These data together with those published for currently marketed cephalosporins were integrated to generate an Intensity Index incorporating both the magnitude and duration that drug concentrations exceed the MIC during steady-state dosing. Cefepime demonstrated comparable or superior indices to cefazolin against Gram-positive microorganisms and to cefuroxime and ceftazidime against Gram-negatives. Serum bacteriostatic and bactericidal activity from the kinetic samples corresponded with the duration that serum cefepime concentrations exceeded the MIC and MBC, respectively, for selected strains. This pharmacodynamic evaluation suggests that cefepime 1 g every 12 h potentially provides inhibitory serum concentrations for the majority of common Enterobacteriaceae, streptococci and S. aureus over the dosing interval but that higher doses or more frequent administration may be necessary for some pseudomonal infections. PMID- 2097716 TI - Simplified monitoring of aminoglycoside treatment. AB - Aminoglycosides are effective but toxic antibiotics. They are usually administered by repeated daily injections with the dosage adjusted according to twice-weakly monitoring of serum concentrations. A recent study involving 60 patients with severe infections proposed simplified administration and monitoring of aminoglycosides. The patients were randomly treated with either gentamicin or netilmicin given by once daily or thrice daily injections. No difference was found in efficacy or in toxicity between the various groups. In drugs excreted by glomerular filtration, the daily dose should be proportional to renal clearance. This we assessed by aminoglycoside clearance, calculated from trough and peak concentrations of the drug in serum. We also estimated creatinine clearance by a simple equation derived from the knowledge that the urinary excretion of creatinine is proportional to the muscle mass, decreasing with age. For women, creatinine clearance (ml/min) should be [150.age (years)].body weight (kg)/serum creatinine (mumol/l). For men less than 70 years, the figure 150 should be substituted by 170, and at 70 years or older, by 160. We used 51Cr-EDTA clearance as an independent arbiter to decide which mode was best suited for monitoring aminoglycoside therapy. The results showed that estimated creatinine clearance corresponded better to 51Cr-EDTA clearance than did aminoglycoside clearance based on assay of serum concentrations (correlation coefficients for patients with single-dose treatment 0.81 vs. 0.72). In the study we monitored aminoglycoside treatment in the conventional manner according to the patient's weight and adjusted the dose after assay of the drug's serum concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097718 TI - Interactions between antibiotics and phagocytosis in bacterial killing. AB - The interaction between antimicrobial agents and phagocytic killing can be studied using three different approaches. The first approach, which is probably the most clinically relevant, is to study intracellular penetration and bioactivity against microorganisms relevant to a particular subcellular 'sequestration' site. The second approach, as yet of uncertain clinical relevance, is to study the toxicological impact of antimicrobial agents on phagocytic functions. This approach has shown that the cell membrane is the target for many enhancing or depressing effects associated with amphotericin B, antimalarials, coumarines, rifampicin and semi-synthetic cephalosporins. Of probable clinical relevance, the third approach is to study the effect on the phagocytic function of preincubating the microorganism. Modification of opsonisation has been the most frequently recognized mechanism, although the release of activating substances and sensitization of the microorganism to oxygen dependent or -independent killing mechanisms have been described. PMID- 2097717 TI - Liposomes and lipid carriers in the treatment of microbial infections. AB - Since antibiotic treatment of severe infections is not always successful, intensification of the antibiotic treatment is needed. Targeting of antibiotics to infected tissues or cells by encapsulation in liposomes is under investigation and may be of importance in the treatment of infections that prove refractory to conventional forms of antibiotic therapy. In animal models of intracellular infections involving the mononuclear phagocyte system--parasitic, fungal, bacterial and viral infections--an improved therapeutic index and reduced toxicity resulting from encapsulation of the antibiotics in liposomes have been demonstrated. By varying the lipid composition of the liposomes it is possible to manipulate their intracellular degradation and thereby the intracellular release and therapeutic availability of the antibiotic. Efficacy of liposome-encapsulated antibiotics in the treatment of infectious diseases outside the mononuclear phagocyte system may be realized by manipulation of the liposome composition. Evidence for this is found in the treatment of systemic fungal infections, in which liposome appear to be very effective as a carrier of amphotericin B. The most advanced application of liposome-based therapy is in this field, and clinical studies with liposome-encapsulated amphotericin B have been in progress for several years. PMID- 2097719 TI - Pharmacokinetic studies of antibacterial agents using the suction blister method. AB - The suction blister technique was used for pharmacokinetic studies with sulfonamides and trimethoprim. Blisters produced by suction (-0.3 kg/cm2) for 1.5 h contained approximately 0.15 ml fluid with a protein content of 40-50% of that in plasma, the main protein fractions being present in the same ratio as in plasma. 2 g sulfaisodimidine was given as bolus injection, i.v. infusion or orally to groups of 4 volunteers. The peak blister fluid concentrations after oral administration (120 +/- 18 mmol/l) was only marginally lower than the concentrations after i.v. infusion (122 +/- 28 mmol/l) and i.v. bolus injections (134 +/- 37 mmol/l). The total drug blister fluid concentration started to decrease before the plasma level was reached. However the relative concentration increased from 53% of that in plasma at 8 h to 66% at 12 h after drug administration. Considering the protein binding of the drugs, the interstitial fluid levels of free drug were presumably higher than the plasma level after 8 h. Comparison of drug concentrations in blisters produced before and after the drugs were given showed higher concentrations in the latter for the first 2-6 h. However, after 8-12 h the concentrations of the drugs in the two types of blisters were similar. The suction blister method produces blisters of uniform size. The drug concentrations in different experiments showed the coefficient of variation for blister fluid concentrations to be no greater than for plasma levels. The consistent results of the standardized suction blister method makes this method useful for studying drug penetration to extravascular compartments in humans. PMID- 2097720 TI - Killing and regrowth of bacteria in vitro: a review. AB - Minimum inhibitory and bactericidal concentrations do not describe the time course of a drug's antimicrobial activity against bacteria. Some antimicrobials exhibit concentration dependent killing over a wide range of concentrations (e.g. aminoglycosides and quinolones), while others show maximal killing at concentrations near the MIC (e.g. beta-lactams and glycopeptides). The aminoglycosides and quinolones can require high drug concentrations (about 10 fold higher than the MIC) to prevent the selection of resistant subpopulations of bacteria. Persistent suppression of bacterial growth after antimicrobial exposure is called the 'postantibiotic effect' (PAE) and varies in duration depending on the drug-organism combination, as well as the concentration and duration of drug exposure. Antimicrobials which are inhibitors of protein and nucleic acid synthesis exhibit prolonged PAEs with a large variety of bacteria. While beta lactam antibiotics demonstrate PAEs with Gram-positive cocci, very short or no PAEs are observed with these drugs with Gram-negative bacilli. The only exception is that penem antibiotics can induce PAEs with some strains of Gram-negative bacilli, primarily Pseudomonas aeruginosa. Thus, the pharmacodynamic activity of an antimicrobial can vary markedly depending on the microorganism and the class of drug and its concentration. PMID- 2097721 TI - Pharmacodynamic effects of subinhibitory antibiotic concentrations. AB - The pharmacodynamic effects of subinhibitory antibiotic concentrations (sub-MICs) on bacteria can be evaluated in different ways. A direct effect in vitro can be expressed as the minimum antibiotic concentration that produces a structural change in the bacteria seen by light or electron microscopy, or as the concentration that produces one log10 decrease in a bacterial population compared to controls. A direct effect of sub-MICs has also been reported in vivo, both in animals with normal host defenses and in humans. In these cases, it has been shown that subinhibitory antibiotic concentrations can be sufficient to clear an infection. Another effect of sub-MICs can be seen when bacteria are pretreated with suprainhibitory antibiotic concentrations and then exposed to subinhibitory concentrations. Here, sub-MICs may produce a long period of delay before regrowth and even yield a bactericidal effect, especially in antibiotic/bacterial combinations where a postantibiotic effect is present. It seems that subinhibitory antibiotic concentrations may be of great importance for the success of intermittent dosing in certain combinations of antibiotics and bacteria. PMID- 2097723 TI - Circulating immune complexes in localised juvenile periodontitis. AB - This study determined the quantity and type of circulating immune complexes (CIC) in the sera of 15 patients with localised juvenile periodontitis (LJP). There was a significantly higher level IgG and IgM in LJP patients as compared with the controls. The possible role of CIC in the pathogenesis of juvenile periodontitis is discussed. PMID- 2097724 TI - Institutional advertising: boon or bane? AB - Dental advertising has long been considered an anathema by the dental profession. However, in recent years, legalisation of dental advertising in the United States and later, Britain, introduced a new dimension into dental advertising. Professional organisations which decided on institutional advertising had reported impressive returns. The benefits and shortcomings of institutional advertising are discussed. PMID- 2097722 TI - Delivery of periodontal therapy by general practitioners in Singapore. AB - The objective of this survey was to determine the capacity of general practitioners to deliver periodontal therapy. This study revealed that only 33% of the dentists surveyed routinely carried out periodontal therapy. The remaining 67% selectively or seldom delivered periodontal therapy. Of the variables investigated, the only variable which played a significant role in the delivery of periodontal treatment was the time since graduation of the dentists, all other factors had no significant influence. 35% of practitioners who had graduated less than 5 years ago routinely carried out periodontal treatment, whereas 50% of practitioners who had been in practice for more than 20 years seldom carried out periodontal therapy. The possible reasons for not delivering periodontal treatment more frequently are discussed. PMID- 2097726 TI - Transpositions of maxillary teeth. AB - Transposition of teeth is a rare and special type of ectopic eruption where two contiguous teeth are found occupying each other's respective normal positions. Nine patients with transposed maxillary teeth are reported. The literature on transpositions, especially on the theories regarding the aetiology, is reviewed. PMID- 2097727 TI - Talon cusp in primary dentition--case report. AB - A case of talon cusp in the primary maxillary left central incisor is reported. This dental anomaly was not associated with any other somatic or dental abnormality. Though pulpal extension into the cusp was detected radiographically, clinical examination after the cusp was ground failed to reveal any pulpal extension. The tooth was badly carious and was restored with a polycarbonate crown. PMID- 2097725 TI - Electrodeposition in dentistry. 1. Background. AB - This paper presents the technical background and research relevant to the electroplating technique. Electroforming is a process whereby a metallized layer is applied to an object via a chemical process referred to as electrolysis. Electrodeposition of dental elastomeric impressions enables a metallized die to be fabricated. Different die materials and techniques exist for the fabrication of dental prostheses via the indirect technique. Electrodeposition of elastomeric impressions offers many advantages, provided an understanding and application of principles is adhered to. PMID- 2097728 TI - Combined granular cell ameloblastoma and plexiform granular cell odontogenic tumour. AB - Granular cell ameloblastomas are uncommon lesions accounting for about 3-5% of all histologic subtypes of ameloblastoma. The plexiform granular cell odontogenic tumour, on the other hand, is a newly described lesion characterised by a monophasic plexiform pattern of granular cells. This article reports a tumour found occurring in the left mandible of a 67-year-old Indian male which histologically showed features of both the aforementioned lesions. PMID- 2097729 TI - Comorbidity of stuttering and disordered phonology in young children. AB - Young stutterers frequently exhibit concomitant speech and/or language disorders. The co-occurrence of these disorders is, however, not yet well understood. The purpose of this paper is to introduce the notion of "comorbidity" as it relates to the field of speech-language pathology: specifically, to discuss comorbidity (coexistence) of stuttering and disordered phonology in young children. Literature on concomitant speech and language disorders in young stutterers is reviewed, with special reference to the prevalence of articulatory/phonological disorders in young stutterers. Future research on the coexistence of two speech and language disorders is encouraged, as well as the consideration of diagnostic treatment and prognostic implications for children who exhibit both stuttering and disordered phonology as opposed to children who exhibit each disorder in isolation. PMID- 2097732 TI - [A comparison of the influence of certain contextual factors on the symptoms of persons with acquired verbal apraxia and verbal developmental apraxia]. AB - Data on the individual symptoms of patients with acquired apraxia of speech and developmental apraxia of speech is of theoretical significance in the study of this disorder. A comparison of individual symptoms may shed light on error patterns in apraxia of speech, the possibility of types of apraxia of speech and on the nature of the disorder. In this study which was part of the wider investigation into the effect of variation in contextual factors on apraxia of speech (Van der Merwe, Uys, Loots and Grimbeek, 1987; 1988; Van der Merwe, Uys, Loots, Grimbeek and Jansen, 1989) the symptoms of four patients with acquired apraxia of speech and one subject with developmental apraxia of speech were compared. The auditorily perceived symptoms and the deviations in voice onset time, vowel duration and utterance duration of all the subjects were compared. The results indicated that the frequency of occurrence of certain symptoms created individual error patterns but also that all subjects had the high occurrence of symptoms which reflect the nature of the disorder in common. The subject with developmental apraxia of speech had all symptoms in common with the other subjects but exhibited less deviancy in the temporal flow of speech and in the duration of the utterance. He presented with more sound substitutions than did the acquired group. The theoretical implications of the results are discussed. PMID- 2097730 TI - Commemorative issue: Prof M L Aron. PMID- 2097731 TI - The development of a framework for assessing developing conversational skills. AB - A framework for investigating the development of conversational skills in children, comprising the areas of topic control, repair of communication breakdown and linguistic cohesion, was devised. This was undertaken by a process of collating information from some existing pragmatic profiles and the developmental literature. The framework was then modified inductively to accommodate features of the data obtained from 12 normally developing English speaking children in the age groups three, four and five years. A number of age related trends emerged that were supported by the developmental literature. This study emphasizes the need for the development of more refined pragmatic assessment procedures which will aid the collection of normative data presently lacking. PMID- 2097733 TI - Stuttering: can research unravel the riddle? AB - In spite of decades of research on stuttering there are few unequivocal findings. Several reasons for this are offered and discussed. Particular attention is paid to the lack of one accepted definition of stuttering. Other issues concern the unit of stuttering, inter- and intra-stutterer variability, the overt and covert features of stuttering, objective and subjective measures in stuttering research and the sampling of material for study. These are some of the problems which pertain to study of the nature of stuttering. They apply also to research on therapy, which presents additional challenges to the researcher. PMID- 2097734 TI - [The influence of otitis media on the central auditory abilities of children with sensory integration problems]. AB - In recent literature otitis media is linked to speech and language problems, behavioural problems and learning disabilities. Until recently limited research has been done in order to determine the influence of otitis media on the central auditory abilities. The aim of this study was to determine whether otitis media has an influence on the central auditory abilities of children with sensory integration problems. Thirteen persons diagnosed as children with sensory integration problems were selected as subjects. They were divided into two groups, namely eight subjects with a history of otitis media (group A) and five subjects without a history of otitis media (group B). A test battery was compiled for evaluation of the central auditory abilities and was used on the subjects. In terms of group A deviating results were obtained on every subtest of the central auditory test battery which indicated a possible brainstem involvement. Group B obtained normal results in more or less all the tests. The results therefore suggest that chronic otitis media has an influence on the central auditory abilities, i.e. in terms of insufficient brainstem functioning. Implications for research and treatment were discussed. PMID- 2097735 TI - The effect of guessing on the speech reception thresholds of children. AB - Speech audiometry is an essential part of the assessment of hearing impaired children and it is now widely used throughout the United Kingdom. Although instructions are universally agreed upon as an important aspect in the administration of any form of audiometric testing, there has been little, if any, research towards evaluating the influence which instructions that are given to a listener have on the Speech Reception Threshold obtained. This study attempts to evaluate what effect guessing has on the Speech Reception Threshold of children. A sample of 30 secondary school pupils between 16 and 18 years of age with normal hearing was used in the study. It is argued that the type of instruction normally used for Speech Reception Threshold in audiometric testing may not provide a sufficient amount of control for guessing and the implications of this, using data obtained in the study, are examined. PMID- 2097736 TI - Methodological considerations in employing the continuous discourse tracking procedure with hearing-impaired adults. AB - This article addresses the various methodological issues involved in the use of the Continuous Discourse Tracking (CDT) procedure as a test instrument for evaluating communication efficiency in hearing-impaired adults. An overview of the potentially confounding variables associated with the CDT technique is provided and consideration is given to the reliability of this procedure with reference to areas requiring systematic investigation. It is proposed that the adoption of an alternative paradigm as well as interdisciplinary approach to test construction may facilitate a multi-dimensional perspective to the assessment of speechreading and communicative ability in the hearing-impaired population. PMID- 2097738 TI - [Curriculum development in speech-language therapy and audiology: basis and principles]. AB - The aim of this article is to discuss some of the important issues that form the basis of curriculum development for education in speech-language therapy and audiology. The demands of the profession are such that a horizontal occupational structure is no longer adequate in the multicultural, multilingual RSA context. It is therefore necessary to investigate alternative educational options to accommodate current needs. These may include diploma training for technicians, certificate programmes for community rehabilitation workers and professionally directed masters courses. It is also apparent that the professional functions of the speech-language therapist and audiologist have extended to the point where aspects such as computer literacy, management functions, community work and consultation should play a greater role in the curriculum than is the case at present. PMID- 2097737 TI - Diagnostic reference data for the monaural brain-stem auditory evoked response (BAER). AB - The objective of the investigation was to establish diagnostic reference data for the normal BAER. BAERs were elicited from the target (R) ear using clicks presented at 70dBnHL. Relevant latency and amplitude data were obtained from 60 selected normal hearing Indian undergraduate females (N = 30; mean age = 20.33 years) and male (N = 30; mean age = 21.33 years) students aged between 18 and 25 years (mean age = 20.73 years). Diagnostic reference data were established for the absolute latencies of peaks I to VI; relative latencies of peaks I-III; III-V and I-V; absolute amplitudes of peaks I and V and the relative amplitude ratio of peaks V:I. These results are discussed in terms of the literature and implications for clinical application and further research. PMID- 2097742 TI - [Hereditary hemorrhagic telangiectasia (Osler-Rendu disease)]. PMID- 2097739 TI - [Effect of ultraviolet irradiation of autologous blood on lipid peroxidation in the prevention of complications after cesarean section in gestosis]. PMID- 2097740 TI - [Efferent methods in the treatment of Lyell's syndrome]. PMID- 2097741 TI - [The blood coagulation system after autologous blood transfusion following aortocoronary shunt]. AB - Fibrinolysis factors were examined in 112 patients operated on for coronary heart disease. After artificial circulation was over,auto- logous blood + was collected in a cardiotomic reservoir and reinfused to the patient. The collected autologous blood was characterized by a manifest fibrinolytic potential, but already in 18 20 hrs after transfusion these changes were undetectable; no enhanced bleeding was observed after surgery. Use of autologous blood helps reduce the necessary amounts of donor blood. PMID- 2097743 TI - [Malignant form of psoriatic arthritis]. PMID- 2097744 TI - [Systemic vasculitis as a complication of hepatitis B]. PMID- 2097745 TI - [ A case of primary hyperparathyroidism]. PMID- 2097747 TI - [A case of paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli syndrome)]. PMID- 2097746 TI - [A clinical case of IgA deficiency]. PMID- 2097748 TI - [Clinical aspects and diagnosis of urocoproporphyria]. PMID- 2097749 TI - [Prominent Soviet surgeon A.T. Lidskii (on the centenary of his birth)]. PMID- 2097750 TI - [A.P. Chekhov--writer and physician-philosopher]. PMID- 2097751 TI - [Polyunsaturated fatty acids in the diagnosis of cardiovascular diseases]. AB - Blood plasma and red cell membrane levels of polyunsaturated fatty acids were measured by gas chromatography in patients with Stage I essential hypertension, borderline arterial hypertension, functional classes II-IV unstable angina pectoris, and unstable angina. The findings suggest that insufficient linolenic acid level in blood plasma and red cell membranes and, in the majority of cases, elevated concentrations of linoleic acid are among lipid metabolism disorders in cardiovascular patients. This fact permits a conclusion that measurements of blood plasma and red cell membrane levels of polyunsaturated fatty acids may be an additional diagnostic criterion permitting an assessment of the disease severity and elucidation of the pathogenesis of coronary disease and arterial hypertension. PMID- 2097752 TI - [Effect of biguanides on the indicators of thrombelastography and the level of lactic acid in diabetes mellitus]. AB - The authors analyze the results of examinations of 232 patients with diabetes mellitus; 48 of these suffering from type I diabetes and 64 from type II diabetes were treated with biguanides. Thromboelastograms were recorded in the presence of hyperglycemia and repeatedly during stable compensation of diabetes, and their values were analyzed with due consideration for therapy administered. Since biguanides are known to induce lactate acidosis, blood serum lactic acid levels were measured when the patients were hospitalized, in the presence of hyperglycemia, and then after a standard exercise test (to detect latent acidosis). When stable compensation of diabetes mellitus was achieved, the examination scheme described before was repeated, i. e. lactic acid measurements before and after exercise test, with due consideration for the therapy administered. Biguanides were found to be conducive to normalization of thrombelastogram values, not elevating the blood serum content of lactic acid even after exercise test. PMID- 2097753 TI - [Effect of the treatment of Cushing's syndrome and primary obesity on the female reproductive system]. AB - Basic parameters of the reproductive system were examined in 121 women with Icenko-Cushing's disease and in 87 ones with primary obesity before and after therapy. Icenko-Cushing's disease was treated with the means acting on the adrenals (chloditan, destruction of one or both adrenals, uni- or bilateral adrenalectomy) and on the hypothalamohypophyseal area (parlodel, peritol, nakom, R-therapy). Combined therapy of primary obesity included low-caloric diet (approximately 1200 kcal) with 1-2 fasting days weekly, a complex of therapeutic exercises, physio- and balneotherapy. The results permit a conclusion that pathogenetic therapy, resulting in a stable clinical and hormonal remission of Icenko-Cushing's disease and body mass reduction in primary obesity as a rule lead to recovery of the reproductive system functioning in such patients. PMID- 2097754 TI - [Diagnosis and treatment of liver abscesses using computerized tomography]. AB - Employment of computer-aided tomography and ultrasonic scanning in 74 patients with liver abscesses helped rapidly detect the condition and identify its type. The sensitivity of ultrasonic scanning in the diagnosis of liver abscesses has made up 90.77 percent, specificity 86.44 percent, in computer-aided tomography these values have been the same and made up 97.96 percent. Closed transcutaneous interventions monitored by computer-aided tomography and ultrasonic scanning in these patients helped reduce the number of complications from 48.78 to 27.27 percent, mortality rates from 29.27 to 3.03 percent, hospitalization periods by 13.21 days, i. e. by 20.6 percent, as against the patients treated by traditional surgical methods. PMID- 2097755 TI - [Arterial hypertension in middle-aged and elderly patients]. PMID- 2097756 TI - [Immunosuppressive therapy of various autoimmune diseases of the nervous system]. PMID- 2097757 TI - [Productivity of using the concept of prognosis]. PMID- 2097758 TI - [Deontological aspects of the organization of the team work in a large multi profile hospital]. PMID- 2097759 TI - [Ambulatory surgery and its prospects]. PMID- 2097760 TI - [Side effects of intravenous laser therapy]. PMID- 2097761 TI - [Effect of calcium antagonists on myocardial contractility in stenocardia]. PMID- 2097762 TI - [Clinico-anatomic parallels in heart defects]. PMID- 2097763 TI - [Status of the stomach and duodenum in persons exposed to low doses of ionizing radiation]. PMID- 2097765 TI - [Changes in the functional and morphological state of the liver in the treatment of acute cholecystitis]. PMID- 2097764 TI - [Intrahepatic arterial infusion chemotherapy in primary and metastatic cancer of the liver]. PMID- 2097767 TI - [Hormonal function of the pancreas in alcoholism]. PMID- 2097766 TI - [Diagnostic value of determining bile acid levels in the blood serum of pregnant women]. PMID- 2097768 TI - [Arterialization of the venous bed in acute critical ischemia of the extremity]. PMID- 2097769 TI - [The vascular and ductal systems of the liver in portal and biliary hypertension]. PMID- 2097770 TI - [Ultrasonographic examination in differential diagnosis of jaundice]. PMID- 2097771 TI - [Errors in the diagnosis and treatment of acute hematogenic osteomyelitis]. PMID- 2097772 TI - [Risk factors of malignant and benign diseases of the breast]. PMID- 2097773 TI - [The speech of Dr. Vojin Sulovic, president of the Serbian Medical Society at the opening of the Serbian Medical Society Building at 19 George Washington Street on 26 November 1990]. PMID- 2097774 TI - [Histologic changes in peripheral nerves in rats with chronic copper poisoning]. AB - The results of histochemical and histopathologic tests of a periphery nerve in rats which were chronically poisoned with copper, are presented. The tests were performed on 45 albino Wistar female rats, which were poisoned with pure copper powder in an inhalation chamber for one year. The control group consisted of 16 rats. By histochemical test the copper pigment was found in 46.66% of the poisoned rats. It was located in epineurium and perineurium, cells and less in the endoneurium. It was also found in cells of the blood vessel media of a periphery nerve. Histopathological changes in a periphery nerve were discrete and they appeared in the form of certain swollen axones. PMID- 2097775 TI - [Acute viral infections: the clinico-immunologic role of high fever]. AB - In acute viral infections with high fever a reduction of body temperature by the action of antithermics effects a brief clinical improvement but shortly the temperature rises again to the levels higher than previously. This indicates an aggravation of the disease. The consequent hyperthermia can be controlled while synchronously the immunologically favorable effect of fever on the activation of the defense reaction of the diseased organism is preserved; this is achieved by a special procedure regulates high febrility. This consists firstly, of lowering all body temperatures above 39 degrees C (measured in the axilla), by the application of lukewarm water compresses around the neck or bathing in the water at 30 degrees C until body temperature is reduced to 38.5 degrees C, after which the bath should be discontinued and the patient left unclothed, lightly covered, at a body T of 38.5-39 degrees C; if the T rises again, the procedure is repeated. The procedure described regulates high fever, promotes clinical improvement and contributes to a favorable outcome of the disease. PMID- 2097778 TI - [The effect of age on in vitro thyroid function tests in adult patients on a chronic hemodialysis program]. AB - The research was designed to investigate in vitro thyroid function tests (TT4, TT3, FT4, FT3, rT3 and TBG) in 14 patients on regular haemodialysis (RHD) and 15 healthy, euthyroid subjects aged 40-59 years and in 17 patients on RHD and 14 subjects aged 60 years and more. Group of older subjects had significantly lower (p less than or equal to 0.01) levels of TT4, TT3 and TBG than group of younger, but those differences were lost between patient groups. Group of older patients had significantly lower level of FT3 than group of younger. Both groups of patients had significantly lower levels of TT3, FT4 and FT3 than both control groups and there was no significant difference in rT3 levels. Age structure markedly influenced difference in TT4 levels and there was also some influence on TBG level. Serum TT4 concentration was significantly lower in both patient groups than in younger subjects group but similar to the level in group of older subjects. The only difference in TBG levels between four groups was significantly lower (p less than or equal to 0.05) TBG level in group of younger patients than in group of younger subjects. PMID- 2097776 TI - [Use of alpha-interferon in the treatment of patients with hairy cell leukemia]. AB - Hairy cell leukaemia is a lymphoproliferative disorder generally involving B lymphocytes and is usually presented by cytopenia. The standard initial therapy is splenectomy that often restores haematologic parameters to normal. Unfortunately, most of these patients manifest relapses with recurrent cytopenia weeks to years after splenectomy. Prognosis of these patients has been completely improved since 1984 when Quesada and his colleagues reported a 100 percent response rate in the first seven patients they treated with partially purified interferon. We report the clinical and immunologic results in 3 splenectomized patients with advanced hairy cell leukaemia treated with human lymphoblastoid alpha n-1 interferon. Two patients showed the leukaemic phase of the disease, and one patient presented progressive pancytopenia with serious infectious complications. The patients were subcutaneously administered 3 x 10(6) U of alpha interferon daily during 16 weeks. After 16 weeks of treatment the patients response was evaluated. They all achieved partial remission of the disease, with normalization of haematological parameters in peripheral blood, circulating hairy cells less than 5%, and reduction of hairy cells in the bone marrow by more than 50 percent in comparison with pretreatment levels. Disappearance of morphological hairy cells from peripheral blood correlated with reduction of B antigen cells, the patients continue to receive alpha interferon three times weekly and future follow-up of these patients will show if alpha interferon will confirm its effect on intermitent dose regimen. PMID- 2097777 TI - [Captopril and enalapril in the treatment of renal hypertension]. AB - Captopril and Enalapril, angiotensin converting enzyme inhibitors, were used in the treatment of grave renal hypertension. The treatment concerned 40 randomly selected patients with the average creatinine clearance of 55.7 ml/min. The patients were divided in two groups: the first groups was ril. The good regulation of blood pressure was achieved only in combination with furosemide and protreated with captopril and the second with enalappranolol. Furosemide was given to all patients, and propranolol to all treated with captopril and to 12 subjects treated with enalapril. The angiotensin converting enzyme increased plasma renine activity and decreased aldosterone concentration in the serum. No change in renal function was noted. Proteinuria was decreased. Side-effects were manifest in two patients only treated with captopril. In conclusion it can be said that angiotensin converting enzyme inhibitors are efficient in the treatment of renal hypertension. PMID- 2097779 TI - [The oral milk provocation test in patients with chronic urticaria]. AB - Histamine and sera complement were followed-up in patients with chronic urticaria during oral provoking test to cow milk. Three patients with a positive history to cow milk sensitisation showed a significant decrease in C3 concentration within 180 minutes of the test. This was followed by increased histamine and skin eruption. According to our results (skin test reactivity and clinical evaluation of the provoking test) several mechanisms were involved in the sensitisation to cow milk in our patients. PMID- 2097780 TI - [Serum antithyroid antibodies in patients with pernicious anemia]. AB - We investigated the incidence of thyroid auto-antibodies and their relationship to antigastric antibodies in 20 euthyroid patients with pernicious anaemia. To evaluate possible thyroid dysfunction we also measured total level of thyroid hormones (TT3 and TT4) and TSH in our patients. Histologic evidence of autoimmune atrophic gastritis and intestinal metaplasia was obtained in 15 patients. We found that it was surprisingly high incidence of thyroid auto-antibodies in patients with pernicious anaemia, particularly in the group with intestinal metaplasia (antithyreoglobulin antibodies 71% and antimicrosomal antibodies 100%). The incidence of antigastric antibodies in these patients was similar to that of those with significant antithyroid antibodies (16/18). Total triiodo thyronine and TSH were significantly higher in the patients with pernicious anaemia than in the control group (p less than 0.05), in the normal range. The results of our study suggest that this upset in immunological physiology is due to a more generalized defect in immune tolerance. PMID- 2097781 TI - [Free-living amoebae of the Naegleria and Acanthamoeba genus]. AB - This is a review of data from literature related to free living amebas, their morphological and biological characteristics and their pathogenic potentials. The aim of this paper is to call attention of clinicians and laboratory workers to these protozoa with regard to the possibility of the onset of some fatal diseases caused by these amebas. PMID- 2097782 TI - [Errors in the diagnosis of Bell's facial nerve paralysis]. AB - On the basis of personal experience, the authors present errors in the diagnosis of Bell's paralysis of the facial nerve. The commentary concerns the causes of these errors and possibilities of avoiding them. PMID- 2097783 TI - [Femoro-axillary bypass in the treatment of subclavian steal syndrome]. AB - Extra-anatomic bypass is a nonanatomic procedure of vascular graft from the donor to the recipient artery. The subclavian or axillary artery is very often used for the revascularization of the lower limbs (axillary-femoral bypass). The usage of the femoral artery for the arm or cerebral revascularization is seldom. The authors describe 74-year old woman with femoral-axillary bypass. The bypass was due to subclavian steel syndrome (cerebral and arm vascular insufficiency). Desobstruction and patch angioplasty of the subclavian artery or aorto-subclavian bypass after, transthoracic approach were a contraindication because of the patients advanced age and subcompensated cardiomyopathy. The authors made no typical extraanatomyc bypasses between branches of the aortic arch (carotidosubclavian, or subclavian-subclavian bypass) because of changes on these arteries (occlusion of the left common carotid artery and stenosis of the innominate artery). This is the reason why the femoroaxillary reconstruction was the only possibility of the cerebral and arm revascularization. The Doppler sonographic and angiographic control examination gave good early, and late results. This case is the confirmation of the good use of this unusual method in surgery of subclavian steel syndrome. PMID- 2097784 TI - [Management of pregnancy in a patient on chronic hemodialysis]. AB - Conception and fetal survival are possible in patients undergoing long term hemodialysis. We report a case of successfully managed pregnancy complicated by maternal chronic renal failure requiring hemodialysis, severe intrauterine growth retardation and polyhydramnios. Pregnancy was terminated by cesarean section at 30 weeks' gestation due to premature labor. A normal-appearing female weighting only 1000 gr was delivered. The infant is now more than a year old and is developing normally. PMID- 2097785 TI - [Aspects of acclimatization of the human body to acute and chronic high-altitude hypoxia]. AB - Exposure of human body to high altitude environment initiate reaction which could be result whether of adaptation or of exhaustion. The purpose is to establish the human body environment which enables regeneration of own cells. Therefore, mechanism of reestablishment of prevention and recognition of symptoms and signs of insufficient adaptability on high altitude are of great interest for clinical and other medical investigators. Special position in research refers on cardiovascular system. Results show, according to effect of only one factor catecholamines, that in course of physical training on high altitude, could be expected, cardiac muscle hypertrophy. It is proved, that under special circumstances catecholamines stimulate synthesis of proteins what enables faster regeneration of the cells. However, under conditions of myocardial ischemia, uncontrolled loading of these patients could lead to deterioration of heart function appearance of cardiac insufficiency. PMID- 2097786 TI - [The cause of death of Wolfgang Amadeus Mozart]. PMID- 2097787 TI - [S.E.M. examination of different grades of curette wear]. AB - After succeeding working trials, a wear test was conducted to evaluate different curettes, by using S.E.M. analysis and replica technique. The obtained results underline the importance of structural characteristics of curettes to maintain standard rates of cutting effectiveness. PMID- 2097788 TI - [Effect of spiramycin on the interbacterial aggregation process in dental plaque formation]. AB - The Authors valued on 18 periodontal patients the bleeding, probing depth, plaque indexes before and after antibiotic therapy with spiramycin. After bacteriological test and coaggregation test the Authors concluded spiramycin all day long is endowed with a good activity in periodontal diseases. PMID- 2097789 TI - [Role of NMR in staging and treatment of extensive myxoma of the upper jaw]. AB - The diagnostical possibilities of the RM in the study of the odontogenic myxoma at extensive diffusion in the upper maxilla are examined. Owing to its complexity and to close connections with the surrounding soft tissues, the midfacial region makes the conventional means of imaging difficult and inadequate. Really the tumor have very high local aggressivity. Where it is much bulky, invades diffusely the cavitary components, damages their walls with laminar structure, insinuates itself among the soft tissues of the jugal, pterygo-maxillary and infraorbital regions, taking up gorges where it slips the classical clinical an also the conventional instrumental diagnostics. The AA. have verified the utility of the MR imaging to the definition of the limits of the tumor, which makes the surgery more adequate to the necessities of an oncological treatment tending both to the radicality and to conservation of structures with high morphological and functional complexity. PMID- 2097790 TI - [Dens invaginatus. Review of the literature and presentation of two clinical cases]. AB - Authors present two cases of dens invaginatus, radicular variety in lateral incisors teeth. They suggest a revision of literature, underlining epidemiological, classifying, clinical and terapeutical aspects of this pathology. PMID- 2097791 TI - [Skeletal growth of young thalassemia major patients treated with intensive transfusion]. AB - The AA. have carried out an investigation on skeletal maturation of children and adolescent with thalassemia major. The data collected in this investigation seem to indicate that skeletal age is quite similar to cronological age in the subjects studied. Furthermore any difference statistically significant as far as growth has been observed between males and of females in our sample. PMID- 2097792 TI - [Use of tissue adhesives in oral surgery]. AB - The Authors, after a short review of the literature, report their clinical experience using alpha-cyanoacrylate, a new tissue adhesive. This substance shows haemostatic and adhesive properties and it is useful to protect surgical wounds. On these bases, the alpha-cyanoacrylate shows definite directions in oral and maxillo-facial surgery. PMID- 2097793 TI - [Dietary habits, dentoperiodontal health index and socioeconomic level in a group of school children]. AB - The Authors evaluate social-economical level, dmft-DMFT, Pl.I., G.I. and alimentary habits of a school-children sample. The findings from the present study indicate that social-economic level influences both prevalence values of dental-periodontal pathology and alimentary habits. PMID- 2097794 TI - [Pedodontic patient: child psychology in relation to the dental sphere]. AB - The Authors emphasize how difficult is for the dental surgeon to approach the young patients. The researches carried out on school children (6-11 years old), of different social conditions, emphasis the psychological reality of the visited children and suggest some contrivances for a less traumatic possible meeting with an unknown world, source of anxiety, stress and fear. PMID- 2097795 TI - [Low power laser biostimulation in chronic oro-facial pain]. PMID- 2097796 TI - Device for serial intraoral radiography with controlled projection angles. PMID- 2097797 TI - [25 years of hospital dentistry at Arhus Community Hospital]. PMID- 2097798 TI - [Arthroscopy and arthroscopic surgery of the temporomandibular joint]. AB - Diagnostic arthroscopy and arthroscopic surgery of the TMJ has during the recent years been introduced in the treatment of internal derangements, preauricular pain and osteoarthrosis of the TMJ. In closed lock cases and in cases with preauricular pain a satisfactory result of treatment has been described in 80-90% of cases, where there was lacking effect of conservative treatment with splints and physiotherapy. The refinement in the technique has made it possible to use rotating instruments, cauterisation and to perform suturing through the arthroscopic cannula and in this way reduce the need for open joint surgery. Due to the technique only few complications have been reported. In the Department of Oral and Maxillofacial Surgery in the University Hospital of Aarhus arthroscopy of the TMJ was introduced 1 1/2 year ago and 22 patients with the clinical diagnosis closed lock or preauricular pain or a combination of these has been treated during this period. The results are satisfactory in most cases and are comparable with previously published results. PMID- 2097799 TI - [Use of titanium osteosynthesis in maxillofacial traumatology and orthognathic surgery]. AB - This paper reviews the clinical use of titanium miniplate osteosynthesis in maxillofacial traumatology and orthognathic surgery. These materials were originally developed for treatment of mandibular fractures, but the application has within recent years been extended to other fractures of the facial skeleton and orthognathic surgery. The osteosynthesis increase stability in many situations, and may reduce or eliminate the need for post-operative intermaxillary fixation, by which morbidity, hospitalization period and period of sick-leave can be reduced. In orthognathic surgery, the stability of the miniplate osteosynthesis increase the demand for precision during surgery as compared to conventional fixation with wire osteosynthesis and intermaxillary fixation. Further refinements of the technique are, however, necessary in the future, as the current techniques does not always allow a sufficient reproduction of the position of the condylar segment. PMID- 2097800 TI - [Treatment of edentulousness by use of osteointegrated implants i e Branemark]. AB - The aim of the study was to evaluate and compare the results of treatment achieved with the Branemark implantsystem in patients treated in our hospital and patients treated in surgical practice. This study includes 96 patients who received a total of 457 implants. Fifty-two patients were treated in the hospital with 304 implants and 44 patients were treated in practice with 153 implants. Most of the patients treated in the hospital received fixed bridges after a total jaw implant reconstruction. In this group complicating medical diseases and severely altered jaw anatomy have influenced the treatment results for which reason 37 (12%) of implants installed were lost. Treatment of partially edentulousness and single tooth loss with implants was dominating in the group of patients treated in surgical practice. In this group only 3 (2%) implants installed were lost. The results of the present study are comparable with other published reports and indicates that Branemark implants has a predictably good prognosis. Furthermore, this study has shown that implant treatment significantly improve the prosthodontic function in patients suffering from edentulousness. PMID- 2097801 TI - [Glass ionomer cement and dentin: effect of pretreatment with polyacrylic acid]. AB - This investigation measured the effect of polyacrylic acid treatment of dentin on adhesion of glass ionomer cement. The dentin was ground on paper No. 220 or No. 500 and treated with a polyacrylic acid solution of 10% or 25% for either 10 s or 30 s. The differences observed in the scanning electron microscope between the differently treated dentin surfaces were not reflected in the bond strength results. Only differences in surface texture due to different coarseness of grinding influenced the adhesion. As to specimens ground on paper No. 220, pretreatment with polyacrylic acid enhanced adhesion of glass ionomer cement. No effect of polyacrylic acid was found on bonding between glass ionomer cement and dentin ground on paper No. 500. PMID- 2097802 TI - [Fluoride effect on bone formation--an overview]. AB - The purpose of this review is to evaluate our present knowledge of fluoride effect on bone formation on basis of the literature. It is likely that fluoride affects the remodelling processes of the skeleton as well as growth related bone formation. During bone remodelling the amount of bone and osteoid tissue is increased by alteration of the balance between resorption and formation. This finding may be accompagnied by impaired mineralization. In studies of fluoride effect on growth related bone formation a number of quantitative histologic alterations have been observed. These include reduction in epiphyseal plate thickness and changes in cellular morphology as well as a retardation of mineralization. The pathogenetic mechanisms behind the observed effects and the variation in tissue response are still unexplained. Fluoride may have a direct cellular effect causing disturbances in cell morphology and metabolism, but the effects may also involve local supracellular mechanisms as well as the general homeostasis of the individual. PMID- 2097803 TI - [Psychosocial working conditions in Landstinget, Kristianstads region]. PMID- 2097804 TI - [Dental health care--valuable resource in combatting diseases related to tobacco use]. PMID- 2097805 TI - [Tunnel preparations. Traditional and alternative methods]. AB - Alternative, conservative techniques for treatment of initial approximal carious lesions in the premolar-molar region are described. Beside the "traditional" tunnel preparation a modified technique is described, in which the proximal enamel wall is left untouched, unless the carious lesion has perforated the amelodentinal junction. The internal Class I-cavity is filled with a radiopaque glass ionomer cement and a composite resin. During 2 years 282 approximal surfaces have been treated and in the 1-year follow-up study is shown that both techniques have sufficient success rate to encourage further use and study. The advantages of these techniques compared to Class II-restorations with amalgam or composite resins are discussed and judged as considerable. PMID- 2097806 TI - [Mouthwash effect on gingivitis and plaque formation]. PMID- 2097807 TI - [Information on dry mouth sufferers. A survey carried out among pharmacists]. PMID- 2097808 TI - [Coronal repositioning of root fragment by root elongation with a titanium endodontic implant]. AB - Teeth with deep transverse or oblique root fractures can nowadays be preserved by intra-alveolar transplantation. This method, however, has its limitation: The apical root fragment must not be too short in proportion to the crown length. This report describes a method to retain even very short roots. 14 roots have been carefully extracted. Then, the following treatment has been performed extraorally: Apectomy, lengthening of the root with a common titanium root screw and replantation of the root in an extruded position which allowed to carry out correct root filling and crown reconstruction. After an average observation period of 19 months 11 cases out of 14, i.e. 79%, were successful according to the criteria stated by Kristersson and Kvint. If the long-term results turn out as promising as the short-term findings, the concept might well be extended to other indications. One example is to stimulate the growth of a genuine periodontal "re-attachment" in intrabony pockets by extruding viable periodontal membrane areas to a more coronal level. PMID- 2097810 TI - [What a cranium can reveal]. PMID- 2097809 TI - [Dental radiographic diagnosis in a district of Sweden]. PMID- 2097811 TI - Pulmonary vascular disease in shunted and nonshunted patients with tetralogy of Fallot. AB - Histometric analysis of pulmonary vascular disease was performed in 13 shunted and 21 nonshunted patients with tetralogy of Fallot, and in 29 normal controls. There was no significant difference in the medial thickness of the small pulmonary arteries between cases of tetralogy of Fallot and normal controls, but the media in shunted cases of tetralogy of Fallot were thicker than in the nonshunted cases. Intimal fibrosis, regarded as organized thrombi, and thrombi of small pulmonary arteries were observed generally after 4 years of age in both the shunted and nonshunted cases of tetralogy of Fallot. Intimal proliferation of musculoelastosis which was formed of longitudinal smooth muscle bundles and elastic fibers was characteristic in shunted patients, especially after the central palliation procedure, Waterston anastomosis or modified Blalock-Taussig (BT) anastomosis using the Gore-Tex tube graft. However, it was not usually seen in the BT anastomosis cases. Unexpected pulmonary hypertension due to the shunt operation is thought to be the cause of musculoelastosis, because musculoelastosis was observed even in a patient with pulmonary hypertension only 3 weeks following surgery. We therefore recommend the original BT anastomosis as the shunt procedure. When considering the use of other shunt operations in which there is a possibility of placing a pressure load on the pulmonary vascular bed, attention must be given to the size of the anastomosis or artificial tube graft. PMID- 2097812 TI - Selection of monoclonal antibodies detecting KM01 antigen. AB - Monoclonal antibodies (MoAbs) were selected for specific binding inhibition of KM01 to the KM01 antigen, which was detected in the serum of colorectal and other gastrointestinal carcinoma patients. Out of 91 MoAbs tested, 8 were found to have the inhibiting activity. The reactivity of these MoAbs with glycolipid antigen, which was isolated from cancer cell line, corresponded well with that of cancer patients sera. These monoclonal antibodies are thought to be useful in combination with KM01 for the construction of the second generation of the KM01 antigen-detecting system. PMID- 2097814 TI - Effects of antiepileptic drugs and organic brain damage on SCE frequency in cerebral palsies. AB - In order to assess the genotoxic effects of antiepileptic drugs (AEDs), analysis of sister chromatid exchanges (SCEs) was performed in lymphocytes of three groups of males; epileptics with AED therapy, non-epileptics without AED therapy and healthy controls. The epileptics and non-epileptics were cases of severe cerebral palsies due to perinatal asphyxia. Possible confounding factors of SCE frequencies, such as age, smoking habit, drug usage other than AED, recent history of viral infection, etc. were controlled. The frequency of SCE per cell was 4.63 +/- 0.71 (mean +/- S.D.) in epileptics, 4.70 +/- 0.89 in non-epileptics and 3.84 +/- 0.56 in healthy controls. SCEs in both epileptics and non-epileptics were significantly higher (p less than 0.05) than those in controls. There was no significant difference of SCE frequency between epileptics and non-epileptics. These results suggested that no mutagenic effect of AED could be demonstrated as revealed by SCEs, and organic brain damage per se might influence the baseline SCE frequency. The possible explanations for such observations are discussed. PMID- 2097813 TI - A family case of nephrogenic diabetes insipidus. AB - Two brothers, patient 1 with fever and vomiting, and patient 2 with failure to gain weight were studied. After 4 hr of water deprivation test, the urinary osmolality of the patient 1 was only 105 mOsm/liter and his body weight showed a 4.6% reduction. In response to desamino-8-D arginine vasopressin intranasal administration, no significant elevation of urinary osmolality of patient 1 occurred. After low dose vasopressin tests, the maximal urinary osmolality of their father was in the normal range, but that of their mother was below the normal range. Moreover, the patients showed no significant increase of urinary osmolality after the same tests. The brothers were diagnosed as nephrogenic diabetes insipidus (NDI) and their mother was diagnosed as a carrier. An early diagnosis of NDI is important, since adequate managements such as low-solute diet with restricted protein and salt intake or such as water intake at frequent intervals can prevent the hyperosmolality which would develop the delayed mental and physical developments. The usefulness of the combination of indomethacin with thiazide diuretics is described. PMID- 2097815 TI - The effect of OP 2507, a stable analogue of prostacyclin, on Hep G2 exposed to hypoxia. AB - We developed a model for screening drugs to reduce ischemic liver damage using Hep G2, a hepatoblastoma cell line, and examined the effect of OP 2507, a stable analogue of prostacyclin, on hypoxic cell damage. Hypoxic exposure of the cells was done for 16 hr in an air-tight chamber which was placed inside an incubator and was purged with 5% CO2/95% N2. Adding OP 2507 (0.01-10 ng/ml) to the incubation medium during hypoxic exposure reduced mitochondrial damage estimated by MTT-reducing activity, while it failed to inhibit lactate accumulation in the medium. OP 2507 seems to be a good candidate for improving the preservation of liver allografts. PMID- 2097816 TI - Subclinical liver dysfunction in one-month-old infants with a low activity of vitamin K dependent coagulant factors assessed by normotest. AB - To clarify features of late vitamin K deficiency hemorrhagic disease in Japanese infants, seventeen of 1,687 infants screened by normotests were examined for signs and symptoms suggesting hepatobiliary diseases. Clinical observations disclosed findings suggesting hepatobiliary diseases in 7 of the 17 selected infants with normotest values of less than 40%, and 11 infants had abnormal results in one or more liver function tests. Taken together, 14 of the 17 infants had findings suggesting hepatobiliary diseases. Upon vitamin K supplementation normotest values improved in various degrees in all infants, whether or not they had signs or symptoms of hepatobiliary diseases. Late vitamin K deficiency hemorrhagic disease of infancy may be related to subclinical hepatobiliary diseases. PMID- 2097817 TI - Activity patterns applied to pollutant exposure assessment: data from a personal monitoring study in Los Angeles. PMID- 2097818 TI - Chloropentafluorobenzene: short-term inhalation toxicity, genotoxicity and physiologically-based pharmacokinetic model development. AB - Ten Fischer 344 rats and six B6C3F1 mice of each sex were exposed to air, 0.25, 0.80, or 2.50 mg chloropentafluorobenzene (CPFB)/liter of air for three weeks, excluding weekends. Exposure to 2.50 mg/liter caused a reduction in the growth rate of rats but did not affect the growth rate of mice. Following the exposure there was reduced SGOT activity in the blood serum of exposed rats and a dose related increase in liver weights. Increased liver weights were observed in mice as well; the response in the female groups was clearly dose dependent. Histologically the livers of both rats and mice presented single cell necrosis. In exposed mice hepatocytes exhibited mild hepatocytomegaly with increased granular eosinophilic cytoplasm. In evaluations for its potential to induce chromosomal damage following this exposure regimen, CPFB did not alter the rate of bone marrow cellular proliferation. Assessment of the micronucleated polychromatic erythrocytes and normochromatic erythrocyte populations during the inhalation exposures indicated a general absence of genotoxic activity. PMID- 2097819 TI - Molecular properties and inhibition kinetics of acetylcholinesterase obtained from rat brain and cockroach ganglion. AB - 1. The molecular composition of acetylcholinesterase (AChE) obtained from cockroach neural, and rat brain tissues was different. Vertebrate enzyme exhibited a higher degree of polymerization than insect enzyme. 2. Acephate was a potent inhibitor of cockroach AChE, but a poor inhibitor of rat AChE. Unlike acephate, methamidophos was a potent inhibitor of both cockroach and rat enzymes. Acephate exhibited greater affinity for the cockroach-AChE than for the rat-AChE, and acephate phosphorylated the cockroach-AChE several times faster than the rat enzyme. The rate of phosphorylation of insect and rat AChE was similar in the presence of methamidophos. Solubilization of AChE by Triton X-100 altered the kinetics of inhibition of rat AChE by acephate. However, solubilization did not alter the kinetics of inhibition of rat AChE by methamidophos or the kinetics of inhibition of cockroach AChE by acephate or methamidophos. 3. The mechanism of acephate-cockroach AChE interaction was different than the mechanism of acephate rat AChE interaction. It is proposed that both the rat and cockroach enzyme may contain, along with the anionic and esteratic sites, an "electron deficient" (ED) binding site which may exhibit selectivity for acephate and nefopam. The ED site in rat-AChE has allosteric properties, whereas the cockroach-AChE does not. It is also proposed that the ED site in cockroach-AChE may be situated in or adjacent to the active site and, therefore, acephate may be bound to the ED site such that the phosphate moiety of acephate interacts with the enzyme's "esteratic" site. Although nefopam also bound to the ED site in cockroach AChE, it did not inhibit the enzyme. This study also indicated that the ED site in rat-AChE may be peripheral to the active site, and that the binding of acephate to this site prevented the phosphorylation by methamidophos of the rat-AChE. Unlike acephate, methamidophos specifically bound to the active site in both the rat- and cockroach-AChE. PMID- 2097820 TI - The exposure-response relationship for mesothelioma among asbestos-cement factory workers. AB - Forty-five deaths from mesothelioma have occurred among production workers in an asbestos-cement factory. This analysis examines the fit of the cubic residence time model to the incidence of mesothelioma using a case-control method proposed by de Klerk and colleagues. The cubic residence time model was found to provide a good description of the data. PMID- 2097821 TI - Asbestos-related radiographic abnormalities in public school custodians. AB - A cross-sectional prevalence study of 120 public school custodians was carried out to investigate the prevalence of asbestos-related disease and to determine the proportion with disease attributable to asbestos exposures in school buildings. Medical and occupational histories, flow-volume loops, and posterior anterior, lateral, and anterior oblique (AO) chest radiographs were obtained. Single breath DLCO was measured and chest auscultation performed. The present report describes radiographic abnormalities and associations with exposure. Mean age of subjects was 57 years and mean duration of work as a custodian, 27 years. Fifty-seven (47.5%) had no known or likely exposure to asbestos outside of their work as a school custodian (NOE). Pleural plaques (PP) occurred in 40 (33%) of the total group and 12 (21%) of the group with NOE. Multivariate analysis revealed significant associations (p less than 0.05) between PP and duration of asbestos exposure. The proportion with PP increased PP detection by a factor of 1.9. Our results reveal PP prevalence in excess of background in the study population and indicate that PP are attributable to asbestos exposure in schools in a subset with NOE. Prudent management of asbestos in buildings is indicated for the prevention of related disease. PMID- 2097822 TI - Drinking water studies of formaldehyde in Sprague-Dawley rats. PMID- 2097823 TI - [Transmammary transfer of nitrates and nitrites in ruminants and methemoglobin blood levels in the young and their mothers]. AB - Transmammary transfer of nitrates was studied in ewes as model animals and in a dairy cow during the colostrum period and shortly after it. Ewes were administered per os 35 mg NaNO3.kg-1 of live weight twice daily during five days post partum and the dairy cow 50 g KNO3 during ten days post partum. Methaemoglobinaemia in ewes and their lambs had consistent dynamics during the whole period of study with slightly higher values in lambs than in ewes. Differences in the averages of methaemoglobin (MtHb) concentrations in blood were statistically higher from the fourth till the 72nd hour after administration. NaNO3 concentration in milk highly and significantly increased after the first administration, with a subsequent decline to an insignificant level during further clays, as compared with the initial data. NO2 ions were not observed to be present in any milk sample. Dynamics of methaemoglobinaemia in the dairy cow and her calf was the same as in the ewes, with a tendency of regular increasing four hours after administration. The increase in methaemoglobinaemia the last day of the trial was at the limit of significance. NaNO3 content in milk significantly increased on the 3rd, 9th and 10th day after administration. Nitrates in urine showed similar trend as in milk with a significant increase only on the 2nd and 10th day post partum. The finding of 14.5 mg.l-1 NaNO3 in the amniotic fluid provides evidence of a simultaneous transplacental transfer of nitrates. PMID- 2097824 TI - [Changes in amino acid levels in bacteria adhering to rumen epithelium in sheep after oral administration of very low doses of mercury]. AB - The effect of low concentrations of mercury taken in the diet (4 mg per a head and day) on the amino acid composition in the proteins of rumen bacteria adhering to the dorsal and ventral parts of the rumen was studied in six sheep. Though the mercury did not influence the amino acid concentration in hydrolyzates of epimural bacteria, low-mercury doses caused significant changes of some amino acids, as compared with the control group of animals. The levels of alanine, histidine, threonine, serine and glycine were significantly decreased and at the same time the levels of proline, valine, isoleucine, tyrosine, lysine and phenylalanine were significantly increased. It was stated in our experiment that the levels of histidine, alanine and threonine in hydrolyzates of epimural bacteria of the rumen were significantly decreased both in the sheep given the balanced feed ration with additions of mercury and nitrogen (according to the standard) and in the sheep given a low-nitrogen diet. Similarly, the levels of proline, tyrosine and phenylalanine in the hydrolizates of epimural bacteria in rumen were significantly increased both with the low-nitrogen diet and in the normal -nitrogen diet with mercury supplement. The results suggest that unexplained disorders frequently occurring in the microbial synthesis in the rumen might be caused by long-continued administration of feed contaminated with extremely low concentrations of heavy metals. The problem deserves detailed investigation in future studies, oriented to explaining the biosynthesis disorders in rumen, reducing the production ability of ruminants. PMID- 2097825 TI - [Changes in free amino acid serum levels in swine during parturition and in piglets during birth]. AB - During the course of parturition seven high pregnant sows, crossbreds of the Large White and Landrace breeds, and their 69 piglets being born, were studied for the changes of the total and separate free amino acids in the blood plasma in relation to the time of duration of the parturition, to the sequence of piglets being born in the litter, and to the birth weight of the piglets. The concentration of the total free amino acids in blood plasma is 2.44 +/- 0.182 mmol.l-1 just before parturition; after the birth of the last piglet it decreases insignificantly to 2.17 +/- 0.190 mmol.l-1. The concentration of the total free amino acids in the blood plasma of newborn piglets is always significantly higher than in their mothers (p less than 0.001) and is 4.24 +/- 0.109 mmol.l-1. The rank of each piglet in the sequence of births in litter has no influence on the level of plasma concentration of the total free amino acids amino acidaemia was 4.03 +/- 0.268 mmol.l-1 in the piglets born first and insignificantly changed to 3.99 +/- 0.445 mmol.l-1 of blood plasma in the last piglets born in the litter. The time factor of parturition is also statistically insignificant. However, the differences in the free "amino acids" concentration in the blood plasma between the piglets with the lowest weight and the piglets with a weight of up to 1200 and 1500 g are statistically significant (p less than 0.02). Alanine (0.43 +/- 0.052 mmol.l-1) and glycine (0.43 +/- 0.063 mmol.l-1) constitute the largest proportions of all the 17 amino acids studied in the blood plasma in the high pregnant sows before parturition. The tyrosine concentration in piglets at birth is remarkably high (1.44 +/- 0.035 mmol.l-1); it represent 34 per cent of the total amino acidaemia. Tyrosine, histidine and lysine concentration in the blood plasma is statistically highly significantly higher (p less than 0.001) in newborn piglets than in their mothers. The phenomenon of 6-times higher tyrosinaemia in piglets, compared with the sows is discussed in connection with the weight at birth and with the data on the function and concentration of thyroid hormones in piglets during the first days of their lives. PMID- 2097826 TI - [Physiologic requirements for casein protein and wheat gluten in 4-month-old rats]. AB - Sources of casein protein and wheat gluten were analysed for the content of proteins, fats, saccharides, water and amino acids. The chemical score of the amino acids and the ratio of essential and non-essential amino acids (E/N) were determined. In rats (males) at the age of 120 days, given the diets for 14 days, the optimal and maintenance physiological daily rations were determined from the changes of body nitrogen, body water and weight dependent on the protein intake, using the method of increasing casein protein and wheat gluten content from 0 to 40 per cent in the diet. In 120-134-day-old rats, the optimal daily dose was 1.75 g of casein protein (7.5 per cent of all proteins in the diet) and 2.46 g of wheat gluten protein (10 per cent of all proteins in the diet). As to the maintenance rations determined from the weight changes, body nitrogen and body water in dependence on the protein intake, in these rats the successive daily rations were 1216 mg, 1214 mg and 1302 mg for the casein protein, and 1731 mg, 1760 mg and 1861 mg for the wheal gluten protein. PMID- 2097827 TI - [Oncologic issues gerostomatology]. AB - In collection value we have analyzed 565 patients above 60 years with malignoms in maxillo-facial area (lip, tongue, big salivary glands, gum, floor of the oral cavity and other strictly undetermined parts of mouth) treated during the years 1978 and 1988 in Central Slovakia. Following epidemiological terms have been studied: incidence, age groups, seasonal occurrence, dimension of the tumors and their stage, time for examination of diagnosis, timeliness of determinations of illness, type of the treatment, time of surviving and causes of death. The number of malignant neoplasms after the age of 60 years is growing. The largest number of malignoms was with Ca of lips, tongue and big salivary glands. Mostly half of the patients looked for the medical help in progressive stadium of the disease. PMID- 2097828 TI - [Our experiences following the absolute augmentation of alveolar ridge by means of cyalith cartilage]. AB - The author presents the results of absolute augmentation of alveolar ridge by means of cyalith cartilage two, four and five years after the surgical operation. The application of cyalith cartilage for this purpose has shown good results. After five years, alveolar ridges have been firm, except in one case, and no atrophy has been observed. Compared with Hydroxyolapatit the cyalith cartilage is much cheaper and the application itself is more simple. PMID- 2097829 TI - [Role of the tongue in the development of open bites]. AB - Forces of the tongue become pathologically effective when they are out of balance with the facial musculature. A rare case of lateral open bite (Figure A) that developed as a result of tongue pressure is described. Treatment with a double plate gave a satisfactory result (Figure D). PMID- 2097830 TI - [Diastema verum and persistent labial frenum]. AB - In the management of diastema verum associated with persistent labial frenum it is important to distinguish, on the basis of clinical testing, between a normal and abnormal labial frenum. The authors believe that from an orthodontic standpoint, frenotomy ad frenectomy are contraindicated in the deciduous dentition. The latter procedure is indicated in a mixed dentition and is best carried out before the eruption of lateral incisors. PMID- 2097831 TI - [Sucking habit--a common mechanical and psychological factor in the development of open bites]. AB - A sucking habit slowly and persistently alters the shape of the alveolar ridge. The changes are so typical that the manner and even the object of sucking can often be inferred from them with considerable certitude. The authors describe an interesting case that was managed successfully with psychotherapy, timely and planned extraction of an upper central incisor, and prosthodontic resharping of the lateral incisor. The final outcome of treatment is illustrated with a photograph. PMID- 2097832 TI - [Clinical experience of composite material use in transcanine area]. PMID- 2097833 TI - [Use of vacuum suction in four handed dentistry]. AB - The author describes the use of vacuum suction in dental suit, where four handed dentistry is performed. He reminds also of the possibility of the danger of iatrogenic damage for the dental pulp. PMID- 2097834 TI - [Prevention of infection caused by hands]. PMID- 2097835 TI - [Sanitary recommendations in dental laboratories]. AB - The possibility of infection in a dental team is great and the sources of infection numerous. This article discusses the possibility of transmitting infectious diseases in a dental laboratory and the self-protection of dental technicians at work. Besides general protective measures and observance of regulations, sanitary recommendations based on the experience of the Berlin University Dental Clinic are summarized. PMID- 2097836 TI - [New cavity designs]. AB - Introduction of new dental materials and new technics cause the changes in cavity preparation and cavity designs especially after introduction of composite resins as a filling material. The majority of changes concern extension for prevention and cavity retention. Occlusal restoration using fissure sealant instead of extension for prevention is discussed as well as a conservative occlusal preparation with no extension for prevention. In addition, other changes in cavity preparation are mentioned in class I to V. PMID- 2097837 TI - [Loss of marginal alveolar bone and tooth mobility]. AB - In the article the relation between initial mobility of incisors of both jaws and the level of marginal alveolar bone is described. The regression lines representing the dependence of mobility on marginal bone level at various loading forces confirm stepwise the nature of the force transmission from tooth to periodontal support tissues. The dependence of regression line slope on increasing inflammatory periodontal pathology indicates increasing loading of alveolar bone over tension of connective tissue fibers as well as increasing of pressure. This can further accelerate alveolar bone resorption. PMID- 2097838 TI - [Treatment of labial herpes with acyclovir]. AB - Recurrent infections with herpes simplex virus (HSV), occurring in as many as 20% of the population, often interfere with dental treatment. HSV (type 1 and type 2) belongs to the family of DNA viruses. The new generation of antiviral drugs promises to provide more successful management of viral diseases. Acyclovir, an analogue of viral deoxyguanosine, is an inhibitor of viral DNA and viral DNA polymerase. The aim of the present study was to evaluate to efficacy of the Virolex ointment, an acyclovir preparation manufactured by KRKA Novo mesto, in the treatment of labial herpes. The results show that Virolex is a highly effective agent. If started in the initial phase of infection it can prevent the development of herpetic lesions. Compared to other antiviral drugs used in the treatment of labial herpes, the duration of acyclovir therapy is shorter. PMID- 2097839 TI - [Evaluation of 10 years action for clean teeth in primary school children in Slovenia]. AB - Teeth brushing isn't the only but is one of efficient means of prevention of caries and gingivitis. The article describes our experience in a unique case of simple, cheap, economical and interesting means for pleasant teeth brushing, after 10 years' duration among Slovene pupils in primary school. PMID- 2097841 TI - [The efficacy of epidemic control measures in eliminating a salmonellosis outbreak]. PMID- 2097840 TI - [Endotoxin-binding systems of the blood]. PMID- 2097842 TI - [Ways to improve the quality of the teaching of microbiology and immunology in medical schools]. PMID- 2097843 TI - [L. V. Padlevskii--microbiologist and epidemiologist]. PMID- 2097844 TI - [The isolation of Yersinia intermedia strains with a plasmid of 82-megadalton molecular weight in natural populations of Yersinia]. AB - For the first time Y. intermedia strains containing plasmids with a molecular weight of 82 MD have been detected in natural populations of urease-positive Yersinia. Such populations have been isolated from two species of birds and from the soil in the area where they have been killed (the Maritime Territory), as well as from washings from the surface of onions in a vegetable store (Chita Province). The strains, administered orally to white mice, proved to be nonpathogenic. Plasmids with a molecular weight of 82 MD are supposed to occur in natural populations of other Yersinia species. PMID- 2097845 TI - [The level of IgM, IgG and IgA antibodies and total antibodies to the low molecular, cell-wall protein of Streptococcus group A without type specificity in the serum of patients with a streptococcal infection]. AB - The levels of IgM, IgG and IgA antibodies, as well as total antibodies, to group A streptococcal low-molecular cell-wall protein without type specificity were studied in the sera of patients with primary erysipelas, rheumatism in the active and inactive phases, seronegative rheumatoid arthritis, as well as in the sera of healthy donors. The average level of antibodies to low-molecular protein in the sera of all groups of patients was significantly higher than the sera of healthy donors. The analysis of the distribution of antibodies in accordance with their isotypes revealed the specific features of response, characteristic of each group of patients. For rheumatism patients, the positive correlation between response to low-molecular protein and response to group-specific polysaccharide A was established. This correlation was most pronounced in patients with rheumatism in the inactive phase. PMID- 2097846 TI - [The characteristics of the biological properties of Shigella dysenteriae 1 circulating in the USSR and India: its biochemical activity and agglutinability]. AB - The properties of 71 S. dysenteriae 1 strains isolated from patients in the USSR and India in 1986-1988 were studied. The cultures possessed typical biochemical and serological properties. As revealed in this investigation, high fastidiousness of this infective agent to the quality of synthetic nutrient could become the cause of false negative reactions in different substrates used for the identification of enterobacteria, thus leading to diagnostic mistakes. The variability of the biochemical activity of different strains with respect to arginine, glycerol, maltose and trehalose (as well as the stability of these signs) was regarded as the theoretical substantiation of the possibility, in principle, to work out the scheme for the subdivision of S. dysenteriae 1 into independent biochemical variants. PMID- 2097847 TI - [The effect of the osmotic pressure of the culture medium on cells of Francisella tularensis vaccinal strain 15]. AB - The dependence of the growth rate of F. tularensis on the osmotic properties of the medium can be presented as a curve with the maximum in the area of 500-600 mOsm. Under these circumstances the intracellular osmotic pressure exceeds the extracellular one by 50-100 mOsm. With the rise of the osmotic pressure in the medium the increase of the concentration of K+ in the cells occurs. The energy dependent accumulation of K+ in the cells at rest is activated by the rise of the osmotic pressure in the medium. F. tularensis are probably capable of osmoregulation, ensured by the energy-dependent osmosensitive K(+)-transporting system. PMID- 2097848 TI - [The status of infectious morbidity in the USSR in 1988]. PMID- 2097849 TI - [The biological properties of monoclonal antibodies to the cytolysin of Legionella pneumophila]. AB - The study of the biological properties of monoclonal antibodies (McAb) to L. pneumophila cytolysin has been carried out. These McAb have been shown to possess no capacity for the in vitro neutralization of cytolysin and the protection of guinea pigs from aerosol infection with L. pneumophila. Still the protective effect of the McAb under study has been observed in experiments with the intraperitoneal infection of guinea pigs, which is indicative of the possibility, in principle, of involving humoral immunity into the protection of the body from Legionella infection. PMID- 2097850 TI - [The tissue heterogeneity of mononuclear phagocyte system cells interacting with Yersinia pestis]. AB - The work deals with the determination of the heterogeneity of cells of the mononuclear phagocyte system, localized in different tissues, in their interaction with Y. pestis. The macrophage populations under study have been found to be heterogeneous in their phagocytic activity with respect to Y. pestis. The digestive activity of alveolar macrophages is considerably lower than that of macrophages localized in other tissues. Macrophages obtained from different tissue are heterogeneous also in the intensity of changes in oxygen-dependent metabolic processes during their contacts with Y. pestis. Alveolar macrophages are less active in this respect than peritoneal ones. Alveolar macrophages under study have been shown to have their own characteristic features; for this reason, the data obtained in the study of one of these populations should not be extrapolated to other populations. PMID- 2097851 TI - [Specific hyposensitization of microbial allergy by using a synthetic artificial polyelectrolyte]. AB - In this work the effectiveness of complex immunotherapy, including specific inhalation hyposensitization with the introduction of artificial synthetic polyelectrolite, was studied. Specific allergen produced a good effect (75%) in the inhalation hyposensitization of hemophilic allergy. The intramuscular injection of artificial synthetic polyelectrolite, made in addition to the inhalation of allergen, produced a better desensitizing effect than the separate administration of allergen or polyelectrolite. The multiple administration of polyelectrolite produced a desensitizing effect on allergic reactions of type I with the tendency towards the decrease of reactions of type IV. Good prospects for the development of methods for special treatment with homologous allergen in combination with NA-5 in cases of microbial sensitization under the control of immunocompetent cells were shown. PMID- 2097852 TI - [The conditions for modern vaccine development]. PMID- 2097853 TI - [Y. pestis phage of a new serovar]. AB - Phage II, isolated from Y. pestis strain 2247 obtained from a desert focus in Central Asia, has been studied. The phage is classified with moderate phages and essentially differs from moderate phages of serovar 2. The sources of isolation, high specificity and the absence of common serological features with presently known Y. pestis phages of serovars 1 and 2 permit the classification of this phage with new serovar 3 of Y. pestis phages. PMID- 2097854 TI - [Conceptual problems in assessing the human immune status]. PMID- 2097855 TI - Technical aspects of electromyography. PMID- 2097856 TI - Electrical injuries to peripheral nerves. AB - As people come frequently into contact with electrical power sources, electrical injuries to peripheral nerves are commonly seen. The authors first review the parameters determining the severity and distribution of electrical injury to nerve tissue. These include tissue resistance, tissue susceptibility, current pathway, type of current, current density, duration and size of electrical contact. Subsequently, the pathophysiology of electrical injuries to nerve tissue is reviewed. Such injuries can be the result of thermal damage, vascular impairment, histological or electrophysiological changes in peripheral nerves, or direct mechanical trauma. Each of these types of injuries causes, specific lesions. As these lesions, especially delayed peripheral neurologic injury, can cause medico-legal problems, it is important to emphasize that electroneuromyography must be performed as early as possible. PMID- 2097857 TI - Electromyography of the external anal sphincter muscle during urodynamic testing in children with meningomyelocele. AB - In this study the correlation between the electromyographic examination of the external sphincter muscle and the urodynamic findings in patients with meningomyelocele was evaluated. Urodynamic testing, consisting of cystometry with bladder, urethral and abdominal pressure monitoring was performed with simultaneous electromyography of the external and sphincter muscle in 61 children, 29 boys and 32 girls, divided in groups according to age and to the level of lesion. Normal urodynamic studies were always correlated with normal external sphincter electromyography. In all patients with a high lesion and in 79% of all others detrusor hyperactivity was correlated with pathological sphincter electromyography. The clinical neurological level of the lesion was not correlated with the function of the detrusor-sphincter mechanism. In 29% of the patients examined with needle electromyography detrusor-sphincter dyssynergia was found, which is less than in most other published studies. And although dyssynergia is a risk factor for renal deterioration, the authors conclude that its effect on the ureter is less important than in subjects with normal perineal musculature, since 80% of the examined patients with meningomyelocele showed pathological sphincter electromyography. These findings thus show a significant correlation between electromyography of the external sphincter muscle and the urodynamic findings in meningomyelocele patients, and clearly demonstrate the importance of urodynamic testing with simultaneous external sphincter electromyography, in order to improve both diagnostic accuracy and reliability of follow-up and treatment. PMID- 2097858 TI - [EMG study of the superior laryngeal nerve distribution]. PMID- 2097859 TI - Electrophysiological examination of the hypoglossal nerve distribution. PMID- 2097860 TI - [Electrophysiological studies of the cricothyroid muscle and the superior laryngeal nerve in voice disorders]. PMID- 2097861 TI - [Posterior interosseous nerve syndrome: a case report]. PMID- 2097862 TI - The anterior compartment syndrome in the lower leg. Review and role of the EMG examination. AB - The Anterior Compartment Syndrome is a relatively rare affection with a wide spectrum of etiologies. Like every compartment syndrome, it is a condition in which high pressure in a rigid osteofascial space reduces capillary blood perfusion so that tissue viability is threatened. When pressure remains sufficiently high for a number of hours, normal muscle and nerve functions become disturbed which may lead to myoneural necrosis. Therefore, an early decompression by means of fasciotomy is essential. Clinical examination is of critical importance in reaching a diagnosis: first of all a painful swelling occurs, followed by muscular paresis or paralysis, and finally loss of sensation and a "silent" electromyogram (EMG). In some cases pressure measurements are necessary, in which tissue pressures over 30 to 40 mm Hg are considered abnormal. The EMG examination is useful in order to achieve a diagnosis and to assess the degree of injury. It may be an important guide for further rehabilitation. PMID- 2097863 TI - [Lumbar hypermobility: where swimming becomes hydrotherapy]. AB - In this paper the authors discuss the clinical problem of lumbar hypermobility. The therapeutical possibilities are resumed briefly. The philosophy of medical training therapy ("Heilgymnastik") is described. More extensive the extra advantages of hydrotherapy (methodical back-stroke swimming) are searched for in a theoretical deductive way. The authors found that: 1. swimming is a low-impact sport so far as the articulations are concerned, 2. back-stroke is done mainly in a lumbar kyphosis, 3. swimming is also an excellent cardiopulmonary training, 4. when swimming the muscles of the shoulder girdle and pelvic girdle are trained in a nearly isokinetic way (power-endurance), 5. the short transverso-spinal muscles are indirectly trained in their tonic more than phasic stretch reflex (posture function), 6. the muscles of the trunk are trained in a nearly isometric way in the appropriate angles (erect position), 7. the position of the head in the water facilitates the abdominal muscles (tonic neck reflex), 8. the cool temperature of the water generates training-enhancing stress-responses, 9. endurance-training is ideal for the postural function of the lower back muscles (especially the deeper layers near the spine) which are anatomical and physiological suited for this purpose, 10. warming-up and cooling-down procedures prepare the neuromuscular, the cardiovascular and metabolic functions before the workout-session (a cold shower afterwards acts to tonicize the skin and muscles). PMID- 2097864 TI - [Sensory conduction study of the supraorbital nerve]. PMID- 2097865 TI - Clinical experience with lonazolac-calcium in the treatment of osteo-arthritis. PMID- 2097866 TI - [Theoretic aspects of infrared therapy approaching athermic pulses]. PMID- 2097867 TI - [Case report: suprascapular nerve neuropathy with isolated infraspinous muscle wasting]. PMID- 2097868 TI - Condensing osteitis of the clavicle. Report of two cases and review of the literature. AB - Condensing osteitis of the clavicle, better defined as aseptic enlarging osteosclerosis of the clavicle, is a rare and benign idiopathic lesion. It is probably of degenerative or mechanical origin, and is most commonly seen in middle-aged women as a tender swelling over the medial one-third of the clavicle. Although the clinical features may be confusing and nonspecific, the typical radiographic and histopathological findings will mostly lead to a correct diagnosis of this disorder. The differential diagnosis is quite extensive. Most difficult to differentiate are: avascular necrosis of the medial clavicular epiphysis, sternoclavicular orsteoarthritis, low-grade chronic osteomyelitis, sternocostoclavicular hyperostosis and Tietze's syndrome. The authors recommend a thorough physical examination and technical tests, not only in subjects with pain of the clavicle but also in those with shoulder pain only, especially in women who are in their fourth decade. Treatment with analgesic and anti-inflammatory medications may be variably effective. In refractory cases excisions of the medial one-third of the clavicle may be indicated to offer better relief of symptoms as well as to exclude malignancy. PMID- 2097869 TI - Evaluation of preoperative hospitalization duration in skin flora. AB - The skin microbial flora of 18 patients was evaluated during prolonged preoperative hospital stay. Five cultures for bacteria and fungi were obtained on different days: on admission one, three and seven days after admission and after skin disinfection with povidone-iodine solution. There was no change in the mean bacterial count from the admission day to seven days after admission. All but one culture obtained following skin disinfection were negative. Pathogenic bacteria were isolated in only one of each of the following culture day: admission, three and seven days after admission. All cultures were negative for yeasts. The findings suggest that the higher rate of wound sepsis observed in patients with long preoperative hospitalization may not be due to bacterial flora change. PMID- 2097870 TI - Oxygen-derived free radical reactions in experimental acute pancreatitis of the dog. AB - Acute edematous and necrotic pancreatitis have been induced in dogs with retrogradely intraductal injections of 5% hydrogen peroxide solution and sunflower-oil. The process of disease could be followed daily by a zipper sutured into the abdominal wound. In this manner the temporal changes of markers of oxygen-derived free radicals (concentrations of malondialdehyde and reduced glutathione of the excised pancreas tissue and abdominal exudate, as well as the superoxide dismutase content of the tissue) could be controlled. Light microscopic analysis was also done. In edematous pancreatitis reversible membrane lesions, in the necrotic form the irreversible damage of membranes and cells could be seen. The results obtained suggest the role of oxygen-derived free radicals in experimental acute pancreatitis. PMID- 2097871 TI - Preserved tendon grafts in reconstructive hand surgery: a review. AB - The authors discuss the use of tendon grafts, primarily in flexor tendon repair, a problem not yet satisfactorily resolved. Criteria for successful non-autogenous tendon grafts are presented, with interest focussing on the immunologic antigenicity of the grafts and the physiologic properties and processes of tendon regeneration. Methods for preserving tendon grafts, including freeze-drying and the use of various chemical agents, are compared and recommended, as well as methods for managing tendon grafting procedures. Questions remaining to be answered in the area of preserved tendon grafts are raised, with suggestions for some answers and avenues for future research. Possibilities for wider clinical applications of the procedure are supported and discussed as well. PMID- 2097872 TI - "Second-look" operations in patients with colorectal tumour. AB - The diagnostic problems of metastases and recurrences in colorectal tumour patients are reviewed. The question and indications of relaparotomies are discussed in detail. The results of relaparotomies made for tumorous and nontumorous indications at the Department of Surgery of the National Cancer Institute are reported. PMID- 2097874 TI - Transvaginal operation of the Stein-Leventhal syndrome: description of a new operative technique. AB - The vaginal operation of the Stein-Leventhal syndrome is presented. The procedure is described. In comparison to the abdominal operation, the new technique has the following advantages: shorter duration of the operation, no scar due to laparotomy, smaller peritoneal wound, and less severe trauma. PMID- 2097873 TI - Thoracic surgery in the elderly: review of 100 cases. AB - One hundred cases surgically intervened due to thoracic pathology between 1977 and 1986 were studied. The ages were equal to or higher than 70 years. Mean age was 73.13 years (70-91). In 70 cases a neoplastic aetiology existed (78.57% of primary bronchial carcinoma), while in the other 30 cases the cause was not neoplastic. In these cases with a high operative risk, a detailed systematic study before surgery is recommended, which should be treated in the most conservative possible way. Although the complication rate was higher than the average in other groups (p less than 0.05), mortality was only 4%, being related, to a greater or lesser extent--, to the surgery (p less than 0.05). In the cases diagnosed as bronchial carcinoma, a 2-year survival was obtained in 66.4%, 3 years in 49.8% and 5 years in 25.7%, concluding that an age equal to, or higher than, 70 years does not represent any contraindication for thoracic surgery. PMID- 2097875 TI - Inflammatory pseudotumour of the liver. AB - In view of their own case, authors review the diagnostic and clinical characteristics of the inflammatory "pseudotumours" of the liver. They state that this liver disease is important from the differential diagnostic point of view. The inflammatory pseudotumours should be basically differentiated from malignant tumours in which the imaging procedures and their repetition are significant. Authors review their case in connection with 13 cases collected from the literature. PMID- 2097876 TI - Changes in hepatic blood flow in jaundice due to hilar carcinomas, the so-called Klatskin tumours. AB - The hepatic circulation of patients with hilar carcinoma and icterus was studied by isotope technique. A marked alternation in blood flow was observed, that is that the ratio of the circulation of the hepatic artery and the portal vein became balanced. By elimination of the icterus, the hepatic circulation normalized. This allowed the conclusion that the change in blood flow must have rather been due to the mechanical icterus and the increased pressure of the bile duct than to the tumorous infiltration and therefore the earliest possible elimination of the icterus is urgently indicated. PMID- 2097877 TI - The influence of clinical and histopathological characteristics upon survival in melanoma patients. AB - The clinical and histopathological features of melanoma were selected which may have an effect upon the 5-year-survival of melanoma patients, and serve as prognostic factors. 165 patients with cutaneous malignant melanoma were analysed and followed up for 5 years at least, during the period 1967-1982. The depth of invasion, tumour thickness, the presence of exulceration and the clinicopathological type of the primary tumour related to complexion have been found reliable prognosticators in order to predict further outcome in terms of minimal and possible 5-year-survival calculated by the life table method. The anatomical site of primary tumours gives a clue to the possible lymphatic drainage and, added to other relevant factors mentioned above, is also helpful in the planning of surgical intervention. Considering measurable prognostic factors of a great significance upon survival, rather additional elective lymph node dissection combined with adjuvant treatment than increased local surgery are advised. PMID- 2097878 TI - Study of the endotoxin sensitivity of pregnant rats and their fetuses. AB - The endotoxin sensitivity of pregnant rats and their fetuses was studied and the following conclusions were drawn: 1. In the third trimester the fetus-damaging effect of endotoxin also involves considerable damage to the mother which often ends with the mother's death (in this experiment in 40% of the cases). 2. The endotoxin sensitivity of the fetuses of one mother is relatively the same. 3. Within the race-specific range the endotoxin sensitivity of a given population of pregnant rats largely varies according to the individual sensitivity. 4. There is no "threshold dose" which would kill each fetus and would not kill any of the mothers. Based also on literary data, it is concluded that the effect of endotoxin causing fetal death is mediated by humoral factors released from the mother's organism, and fetal death is primarily due to anoxia. PMID- 2097879 TI - The role of Ca2+ level in liver transplantation. AB - During orthotopic liver transplantation Ca2+ assessment was made in the recirculation phase and the ultrastructural changes in the liver were studied. It was established that the Ca2+ level decreased progressively. The Ca2+ level in the hepatic vein was lower than the arterial value. The EM studies performed in the recirculation phase did not reveal any cellular damage, only the swelling of the mitochondria was striking. Based on the results, the question was raised whether Ca2+ can have a prognostic role in assessing the viability of the liver. PMID- 2097880 TI - [The cephalic arterial system in dogs, especially on the anastomoses between the intracranial and extracranial circulations]. AB - The cephalic arterial system with a special reference to the anastomoses between the extracranial and intracranial circulations was investigated by means of the corrosion casts of 30 dogs. We researched into the cephalic arterial system in dogs according to Bugge's theory. His theory is as follows: ontogenetically it is composed of 4 arterial systems (the internal and external carotids, vertebral and stapedial arteries), although these arteries trans-figure from the primitive basic pattern to the adult one with particular anastomoses between the branches in each of the species. The modification of this basic pattern occurs as a result of the obliteration or persistence of certain parts of the 4 original arterial systems when they are accompanied with various anastomoses. And he emphasizes that the mode of the appearance of each anastomosis is constant in each of the species. In this paper the obtained result is as follows. The stapedial artery that occurred in an early stage of embryonic period obliterates the proximal part except for the supraorbital, infraorbital and mandibular branches. Anastomosis X between the vertebral and external carotid arteries is formed in all the cases. Anastomosis Y between the internal carotid and ascending pharyngeal arteries is found at 20% on the right side and 30% on the left. Anastomosis a1 between the internal ophthalmic artery and each of the orbital arteries derived from the supraorbital branch is recognized at 93% on the right side and 97% on the left, and the other a1 between the internal ophthalmic artery and anastomosis a6 is formed in 7% on the right side and 3% on the left. Anastomosis a2 between the supraorbital and infraorbital branches is recognized in all the cases. Anastomosis a3 between the distal part of the external carotid artery and the proximal portion of the mandibular branch is found out in all. Anastomosis a4 between the distal portion of the internal carotid artery and the supraorbital branch or each of its distal branches in the orbita is recognized at 90% on both sides. Anastomosis a5 between the distal part of the internal carotid artery and the proximal part of the infraorbital branch or the middle meningeal artery is found at 97% on the right side and 87% on the left.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2097881 TI - [Smoothed skeletal maturity curve of Japanese children by Tanner-Whitehouse 2 (TW2) method and its application]. AB - This paper reports the TW2 skeletal maturity status on some 8,800 Ogi schoolchildren aged 6.5-17.5 years, who participated in the 1979-1988 Ogi Longitudinal Growth Study. The smoothing B-spline function was applied to 3, 10, 25, 50, 75, 90, and 97 percentile TW2 RUS, carpal and 20-bone scores. The carpal maturity pattern was variable throughout the periods. The RUS matured with narrower variation during preadolescent period, then became variable with advancing age. The dispersion of the 20-bone score converged toward post adolescent period. Ogi children showed retarded skeletal maturation compared with British standard during preadolescent period, then the children have surpassed the standard at adolescence. The skeletal maturity status of Ogi children was not identical with that of two Chinese samples. Harbin and Beijing children. Ogi girls showed similar maturity pattern to Harbin girls, but Ogi boys retarded in the RUS score compared with Harbin boys during preadolescent period. Ogi girls retarded in the TW2 20-bone bone age at ages 7-9 years, then they surpassed Beijing girls. Ogi boys always exceeded Beijing boys during the period of 7-17 years. Tokyo children in 1960s surpassed the Ogi children during whole periods studied. Tokyo children in 1980s exceeded Ogi children only at postadolescent period in boys, and they retarded during adolescent period in girls. I examined a possible secular change in the skeletal maturation with a cohort analysis of Ogi children. The median test revealed the secular change only at the specific cohorts and age classes, but not general secular trend of acceleration of the skeletal maturation. I examined the socioeconomic influence to the skeletal maturation within Kyushu populations, Naze, Nomozaki and Ogi children. Although Ogi and Naze samples showed similar socioeconomic status, their skeletal maturity status differed significantly. Ogi and Nomozaki children showed similar skeletal maturity pattern irrespective of their socioeconomic discrepancy. PMID- 2097882 TI - [The immunostimulating action of suramin in infection with the infectious rhinotracheitis virus]. AB - The immunostimulating antiviral preparation suramin has a favourable effect on the process and outcome of an experimental infection with the virus of infectious rhinotracheitis (bovine herpes virus type 1, BHV1), thus reducing the gravity of the clinical course and increasing the survival rate. The therapeutic protective effect of the preparation is expressed in the prevention of virus-induced immunosuppression which is markedly strong during the acute phase of the infection process. Suramin restored the number, viability, relative share in the bronchial lavage population, phagocytic and microbicidal capacity of the alveolar macrophages--a major factor of the local defence mechanisms of the lung. In a similar way suramin influenced some parameters of the systemic immunity (number and differential count of polymorphonuclear phagocytes, plaque- and rosette forming cells). The application of suramin in doses lower than those used for virus inhibition and its considerable action on different mechanisms of the immune system suggested that the preparation's therapeutic effect could be related mainly to its immunostimulating properties. PMID- 2097883 TI - [The immunomodulating properties of a macro glycopeptide isolated from serum. II. The activation of macrophages and polymorphonuclear cells]. AB - The stimulating properties of three fractions of a glucomacropeptide consisting of different carbohydrate and peptide components were studied. The phagocytic activity of polymorphonuclears was increased on the 24th hour and of macrophages on the 3rd day after application of the preparations to mice. In vitro fraction 3 stimulates the lysozyme activity and the synthesis of proteins and Clq of the macrophages complement. These properties of the cells are collaborated by the established ultrastructural changes. The different composition of the fractions determines their immunostimulating effect. PMID- 2097884 TI - [The phage sensitivity and insecticidal activity of local strains of Bacillus sphaericus]. AB - The sensitivity of 132 local isolates of B. sphaericus to phages 3, 4 and SST of A. Yousten has been studied. According to this incomplete phage typing, most of the strains are classified in the third phage group. A high-degree correlation between sensitivity to phage 4 and insecticidal activity was established, owing to which this sensitivity can be used as an initial criterion for selection of newly isolated strains. LC50 and LC90 of one reference and six local strains of B. sphaericus were determined using Culex pipiens third instar larvae, and the local strains were found to exceed in insecticidal activity the reference strain 2362. This suggests that the newly isolated strains are promising for developing of a preparation for biological control of mosquitoes. PMID- 2097885 TI - Why are so few patients with epilepsy treated surgically? A United Kingdom perspective. AB - The reasons why many patients with drug resistant complex partial epilepsy who might benefit from surgery are not appropriately assessed are examined, and include the attitudes and prejudices of Neurologists, Neurophysiologists, Neuroradiologists, Neurosurgeons and the patients themselves. Finally, the implications of provision of the necessary resources in the United Kingdom are presented. PMID- 2097886 TI - Temporal lobectomy. AB - The indications for, and results of the author's personal series of 486 resective operations in epileptic patients are reviewed, together with the long term results of 286 patients undergoing temporal lobectomy. Almost 50% of such patients were seizure free when followed for two to thirty years. PMID- 2097887 TI - The Zurich amygdalo-hippocampectomy series: a short up-date. AB - Selective amygdalohippocampectomy was developed as a surgical treatment for temporal lobe epilesy with a well-defined unilateral mesiobasal limbic seizure onset. Since 1975, 236 patients have been operated on in Zurich. We briefly summarize recent studies on the seizure outcome with analysis of the postoperative long-term fluctuations in relation to postoperative anticonvulsant drug treatment, on the underlying neuropathology, and on the relationships between magnetic resonance scanning estimates of total volume of the removed tissue and the resection scores of amygdala, hippocampus and parahippocampus gyrus. PMID- 2097888 TI - Problems of drug surveillance--an international view. AB - The importance of Post Marketing Surveillance (PMS) is stressed, both to determine the therapeutic value of the drug and its adverse effects revealed in a large population of patients. A survey of such adverse effects of anti-epileptic drugs is provided: metabolic, dose-related and idiosyncratic. Problems of monotherapy and of drug interactions are discussed, as well as questions of central nervous system toxicity and of teratogenicity. PMID- 2097889 TI - Neuroradiology including magnetic resonance. AB - The radiological assessment of drug resistant temporal lobe epilepsy has changed dramatically over the last few years. New CT scan techniques and the increasing application of MRI have meant that ever more subtle lesions can now be regularly identified. The major challenge now lies in the accurate identification of atrophic lesions such as Ammon's horn sclerosis. PMID- 2097890 TI - SPECT in the presurgical evaluation of patients with temporal lobe epilepsy--a preliminary report. AB - Twenty-eight patients with drug resistant temporal lobe epilepsy (DRTLE) were studied using single photon emission computed tomography (SPECT) using xenon-133 inhalation and Tc99m-d, 1-HMPAO with TOMOMATIC 64 as part of a presurgical evaluation programme. The visually evaluated flow-images were studied after blinding and the results subsequently compared to the EEG, MRI and CT scanning studies. In 24 patients a significant low flow region was seen in one temporal lobe. The SPECT result corresponded to the EEG findings in all but 6 patients. In 2 of these patients no side localization was indicated by EEG, while in four patients the EEG suggested that the opposite side was epileptogenic. Ictal SPECT and MRI/CT agreed with the resting SPECT study in three patients, while one patient has remained undiagnosed with respect to side-localization. In 14 patients discordance between SPECT and the CT scan was observed, but in 11 of these patients the SPECT study correlated with the other focal diagnostic tools. In 11 of the 21 patients studied by MRI, the results corresponded to SPECT; in 7 of the 10 which did not correspond, ictal studies of EEG and SPECT defined the side, in four of these 7 patients. Using the neuroimaging tools in concert 16 patients have been selected for surgery. All patients have benefited from surgery. These preliminary results correspond favourably with earlier studies comparing SPECT and PET with CT, MR and EEG. PMID- 2097891 TI - Quantitative analysis of 18/FDG-PET in the presurgical evaluation of patients suffering from refractory partial epilepsy. Comparison with CT, MRI, and combined subdural and depth. EEG. AB - CT, MRI, 18/FDG-PET and Depth. EEG, performed with subdural and depth electrodes were part of the presurgical evaluation in 22 patients. Statistical analysis of 18/FDG-PET was performed to compare cerebral utilization of glucose to that of normal age matched controls. The findings of CT, MRI, and quantitative analysis of PET are compared with those of ictal Depth. EEG. A positive correlation between CT and Depth. EEG was obtained in 23% of the patients and between MRI and Depth. EEG. in 50%. For both imaging techniques a negative correlation was found in 5%. Regional abnormalities were found with quantified PET in 95% of the patients and were concordant with Depth. EEG. for side of onset in 77% of the patients and for lobe of onset in 59%. A possibly false localising PET result for lobe of onset was obtained in 8 patients (36%). Limitations of PET were most apparent in patients with regional mesiolimbic or bilateral seizure onset. A favourable outcome of surgery was associated usually with positive convergence of both methods. PET may be a valuable contribution to the research and management of partial complex epilepsy, but at present cannot be considered a reliable alternative to invasive EEG methods in patients without clear unilateral focus localization on surface EEG. PMID- 2097892 TI - Chemotaxis of leukocytes from peripheral blood of patients with juvenile rheumatoid arthritis (JRA). AB - Spontaneous and stimulated migration of leukocytes from peripheral blood was studied in 15 patients with JRA and 15 controls. Cells from both groups showed equal migratory ability. However, in the presence of the activated serum of the JRA patients, there was a significant decrease in migration of leukocytes from JRA patients and from controls, suggesting the existence of a serum factor responsible for this chemotactic impairment. The effect of washing on the migration of these cells was also studied. A significant decrease could be observed in the spontaneous and stimulated migration of washed cells from both JRA patients and controls. PMID- 2097893 TI - Mitigating effects of dialysable leukocyte extract (DLE) on the experimental allergic uveitis (EAU) of the rabbit. AB - Experimental allergic uveitis (EAU) is an induced autoimmune disease by administering soluble retinal S antigen and complete Freund's adjuvant (CFA). In rabbits, the result is the occurrence of chorioretinitis in 90% of the cases. The first inflammation is followed by spontaneous relapses. The EAU of the rabbit was utilized to study the effects of the dialyzable leucocyte extract (DLE) on the course and the intensity of the disease in this autoimmune model. The DLE preparations examined differed with regard to their origin or the immunological stimulation of the initial material (DLE from humans (DLE Hu) and DLE from the normal rabbit (DLE RaO) or rabbits which had EAU (DLE RaEAU) and rabbits which had received CFA (DLE Ra (CFA). One unit of DLE corresponds to the extract from 10(9) cells. The administration of DLE starts with the onset of inflammation. 4 x 0.5 units were administered during the first week, 1 x 0.5 units per week from the 2nd to the 12th week. All preparations decrease the cumulative frequency of the days of illness significantly. The duration of the initial inflammation is reduced in all animals treated, but only in part significantly. There appears a graduation of efficacy: DLE RaEAU greater than DLE Ra CFA greater than DLE Hu greater than DLE RaO. Overall, it can be seen that, on the one hand, there is no specificity or restriction of the species for the efficacy and, on the other hand, the extent of the effects depends on the degree of the immunological stimulation. The maximum efficacy of DLE RaEAU is not exclusively due to the transmission of an antigen-specific sensitization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097895 TI - Measurement of response to methacholine inhalation challenge in asthma and allergic rhinitis. PC20 or PC35FEV1? AB - It has been widely accepted that significant bronchial responsiveness is demonstrated by a 20% fall in the FEV1 during the course of a methacholine challenge (PC20 or PD20FEV1). However, many subjects with allergic rhinitis may have a positive reaction, as evidenced by attaining a PC20 or PD20FEV1, and then demonstrate a plateau. When the PC35FEV1 is used, individuals with this plateau versus individuals with asthma can clearly be differentiated. We thus decided to assess bronchial responsiveness to methacholine with PC20 and PC35FEV1 in asthmatics and patients with allergic rhinitis. Bronchial challenge with methacholine by the method described by Cockcroft et al., with a Hudson 1720 nebulizer (output: 0.198 +/- 0.017 ml/min) was performed on 57 asthmatics and on 56 patients with allergic rhinitis. At the time of the study, they had an FEV1 and FVC greater than or equal to 80% of their predicted normal value and a FEV1FVC% greater than or equal to 70%. Results were expressed as the provocative concentration of methacholine required to produce a 20% and 35% fall in FEV1 (PC20 and PC35FEV1). A plateau was considered if 3 or more consecutive doses of methacholine produced no fall in FEV1 greater than 5%. By the PC20FEV1, bronchial responsiveness was increased (PC20 less than or equal to 18 mg/ml) in 98% of patients with bronchial asthma and in 28% of patients with allergic rhinitis. By the PC35FEV1, bronchial hyperexcitability (PC35FEV1 less than or equal to 40 mg/ml) was detected in 93% of patients with bronchial asthma and in 12% of patients with allergic rhinitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097894 TI - Efficacy of sublingual immunotherapy in patients with rhinitis and asthma due to house dust mite. A double-blind study. AB - Fifty eight patients under 12 years of age, positive to mites (Dermatophagoides pteronyssinus and D. farinae) according to prick, "in vitro" specific IgE and challenge tests, suffering from asthma and rhinitis, were randomly assigned on a double blind basis to receive per os either a biologically standardized extract of mites (active therapy TA = 30 patients) or a saline buffered solution (placebo = 28 patients). Patients took sublingually increasing doses of the solution, followed by maintenance therapy consisting of 15 drops 3 times a week. The results of the trial were assessed after 12 an 18 months, according to the following parameters: symptom scores recorded in diary cards, total and specific IgE levels, total IgG level, IgG1 and IgG4 levels, lymphocytes underpopulations, nasal challenge test, side effects. During the first 18 months, the patients on active therapy had significantly lower scores (p less than 0.001) and clear variations of rhinomanometric parameters (p less than 0.01); IgG also significantly increased. After 12 months, bronchial specific and specific challenge tests showed significantly higher threshold values in comparison to initial values (p less than 0.05). No statistically significative variation was registered in the placebo group. PMID- 2097896 TI - Childhood asthma and outdoor air pollution in Oporto area. AB - The influence of outdoor air pollution, on childhood asthma, is not yet completely understood, especially a long exposition to low but persistent pollutants levels. This paper presents the relationship between air pollution, as sulphur dioxide (SO2) and black smoke (BS), and asthmatic attacks on children living in the Oporto area, during the period between 1983 and 1987, when its levels ranged below the official "security" ones. There was no correlation between daily levels of SO2 or BS, and the asthmatic attacks rate. However, for longer periods, as months and quarters, an increased positive correlation was found, but only with SO2 (r = 0.334, p = 0.01; r = 0.473, p = 0.07, for month and quarter periods, respectively). These data suggest that, neither SO2 nor BS seem to be direct bronchospasm inductors, at least when its levels stay between the relatively low limits observed. On the other hand, the longer exposition to SO2 appears to lower the threshold of the asthmatic children to other bronchospasm stimulus. PMID- 2097897 TI - [Relationship between the immune system and heat shock proteins. A literature review]. AB - Heat shock proteins (HSP) or stress proteins are produced by prokaryotic and eukaryotic cells in response to a variety of environmental stressors. The heat shock response is one of the most universal reactions known and heat shock proteins are among the most conserved molecules in phylogeny. Recent findings concerning the immune response to heat shock proteins are discussed especially with respect to the role of HSPs postulated in septic disease and inflammation, in antipathogenic immunity and in the induction of autoimmune diseases. Results and speculations considering a relationship between HSPs and gamma/delta T cells or polyreactive antibodies, possibly as part of a phylogenetic old immune system, are critically reviewed. PMID- 2097898 TI - [Affinity chromatographic purification of streptokinase with monoclonal antibodies]. AB - Monoclonal antibodies against streptokinase as ligands were coupled to different matrices. Both CNBr-activated Sepharose and macroporous bead cellulose activated by carbonochloridate revealed as suitable for purification of streptokinase by affinity chromatography. Immunoadsorbents with a higher concentration of the coupled ligand were more effective than those with a lower. For streptokinase optimal conditions of binding and elution without negative influence on structure and activity were ascertained. A buffer with slight alkaline pH was successful for desorption. Using this method it was possible to obtain pure streptokinase from several streptokinase containing media. PMID- 2097899 TI - [IL-2 production by peripheral blood mononuclear cells after stimulation with pokeweed mitogen]. AB - Peripheral blood mononuclear cells were cultured for 72 hours in presence of phytohaemagglutinin (PHA), phytohaemagglutinin/phorbolmyristate acetate (PHA/PMA), pokeweed mitogen (PWM) and in absence of these stimulators. The IL-2 concentrations of cultural supernatants were determined by an IL-2 dependent cell line. There was no IL-2 determined in absence of any mitogenic stimulators. Induction of IL-2 by PWM does not require the presence of PMA in contrast to stimulation by PHA/PMA, where PMA was found to be necessary for stimulation of production of IL-2. PHA/PMA induced IL-2 release shows only a weak maximum at 24 hours, whereas PWM induced IL-2 release was found to have a clear maximum at 48 hours. Stimulation by PWM enables comparative examination of DNA synthesis (lymphocyte transformation test) and IL-2 production in the same cell system using only one mitogen. PMID- 2097900 TI - Detection of antibodies to islet cell and splenic lymphocytes in diabetes-prone BB and adjuvant-streptozotocin treated Lewis rats by ELISA and immunoblot analysis. AB - An enzyme-linked immunosorbent assay (ELISA) has been developed to detect antibodies against surface components of rat islet and spleen lymphocytes. Live islet tumor RIN5 AH cells expressing characteristic ganglioside target antigens or rat spleen cells were immobilized onto wells of microtiter polystyrene plates precoated with poly-l-lysine and then incubated with test or normal rat sera. Cell surface-bound antibodies were quantitated after reaction with horseradish peroxidase-conjugated rabbit anti-rat Ig. With this assay, 46% (6/13) of sera from diabetes-prone BB rats and 100% (8/8) of sera from rats treated with complete Freund's adjuvant/streptozotocin (CFA/STZ) prior to immunization with RIN cells had islet cell surface antibodies: 54% (7/13) and 75% (6/8), respectively, were positive for lymphocyte antibodies (defined as the HRP anti rat Ig binding exceeding the mean + 2SD of control group values). SDS polyacrylamide gel electrophoresis followed by immunoblotting analysis suggested that the islet cell antibodies in sera from the BB and CFA/STZ rats recognized RIN-cell components that were different in their molecular weights. These antigens were not detectable on spleen cells indicating that the ELISA described can be used to quantitate levels of islet cell specific antibodies which possibly reflect beta cell damage with progression to islet degeneration in the rat. PMID- 2097901 TI - [Immunoenzyme assay of parasite-specific IgG4 antibodies in schistosomiasis using the monoclonal antibody BL-IgG4/1]. AB - Sera from 251 children living in endemic areas (Schistosoma mansoni or Schistosoma haematobium) and from 188 hospital outpatients in Ethiopia were evaluated for specific IgG4 antibodies reacting with Schistosoma mansoni adult worm antigen employing an enzyme-immunoassay. Patients with schistosomiasis (n = 140) possessed a significantly higher mean value of specific IgG4 antibodies than normal controls (n = 30) and individuals from different countries who had no schistosomiasis but are infected with other parasites (n = 114). Blood samples dried on filter paper were also acceptable in these test. The use of the test in diagnosis is compared and assessed with parasitological methods. PMID- 2097902 TI - [Production and characterization of a high affinity monoclonal antibody with digoxin and digitoxin specificity]. AB - A monoclonal antibody with a high affinity for digoxin (KA = 5.5 x 10(10) M-1) and digitoxin KA = 5.0 x 10(10) M-1) was produced by somatic cell fusion. This antibody, designated 2A3, displayed little cross reactivity with other glucosides and no cross reactivity with endogenous steroids. It was shown that 2A3 is a suitable tool in an enzyme immunoassay for digoxin and digitoxin. PMID- 2097903 TI - [Staphylococcus aureus (STA), a B- and T-cell mitogen]. AB - Mitogenesis in peripheral blood lymphocyte and separated T and non-T cells cultures activated with formalin-fixed and heated staphylococcus aureus strain 520 (STA) was studied. The peak of DNA-synthesis in presence of STA is on day 7. The maximum of proliferation was found for T cell on day 7 and for non-T cells on day 3 after stimulation with STA. We found a strong correlation between the expression of CD25 antigen and the 3H-thymidine incorporation. It is concluded that B and T cell proliferation can be studied without purifying the cells using the different proliferation kinetics in presence of STA. PMID- 2097904 TI - Therapeutic strategies for cancer pain management. AB - Clinical issues related to treating the oncology pain patient have gained considerable attention in the medical and health care literature. Addressed are management strategies which focus specifically on cognitive-behavioral, psychosocial, and pharmacologic approaches to treating the oncology pain patient. Each strategy possesses unique qualities that can benefit the care and management of the cancer patient and provide a better understanding of the disease entity and the patient's ability to develop coping strategies that may be effective in understanding and confronting pain associated with cancer. PMID- 2097905 TI - Psychedelic effects of a subanesthetic concentration of nitrous oxide. AB - The subjective effects of nitrous oxide were examined by administering questionnaires to volunteers (16 men and 16 women) breathing 30% nitrous oxide or 100% oxygen. Nitrous oxide produced a variety of subjective effects, including some that are characteristic of psychedelic drugs, such as happy, euphoric mood changes, changes in body awareness and image, alterations of time perception, and experiences of a dreamy, detached reverie state. The subjective effects, including those of a psychedelic nature, were very similar to the subject effects we observed in a previous study of nitrous oxide. However, euphoric mood changes were more pronounced, and adverse effects were less pronounced, in the present study, possibly due to the shorter duration of gas inhalation or the minimal tests of performance involved. Some other differences in subjective effects between the present and previous studies were identified by a discriminant analysis and seemed related to specific differences in experimental conditions. This suggests that the environment can influence which drug effects emerge, or at least their relative prominence. Clinicians should be familiar with the range of subjective effects that patients inhaling nitrous oxide may experience. PMID- 2097906 TI - Absorption and elimination of midazolam by submucosal and intramuscular routes. AB - The purpose of this investigation was to compare the rate of absorption and clearance time of midazolam (Versed) when administered by the submucosal (SM) route), and the intramuscular (IM) route in ten healthy adult volunteers, ranging in age from 25 to 35 years. Each subject received midazolam 0.08 mg/kg, to a maximum of 5 mg, by the SM and IM routes at two week intervals. Vital signs and arterial oxygen saturation levels were monitored every five minutes throughout the 180 minute study period. Blood samples (3 ml) were collected via an intravenous line, prior to midazolam administration and at 2, 5, 10, 20, 30, 45, 60, 90, 120, 150 and 180 minutes, centrifuged and analyzed by gas-liquid chromatography. The mean absorption rates and the mean elimination times of the two routes were not significantly different. The mean peak absorption was reached at 10 minutes by the SM route (80.4 ng/ml) and at 20 minutes (92.0 ng/ml) by the IM route, with considerable individual variability. Vital signs were stable throughout the study period in all subjects with both routes. All subjects reported pain at the injection site during SM injection which continued for up to 48 hours. No pain related to the IM injection was reported. PMID- 2097907 TI - Sensory experience induced by nitrous oxide analgesia. AB - Preliminary findings on a group of 15 dental patients, treated with nitrous oxide indicated frequent occurrence of several, well-defined sensory experiences related to various modalities. A subsequent controlled experiment carried out on 44 volunteers, inhaling a 35% N2O + 65% O2 sedative gas-mixture as well as O2 alone in two different sessions confirmed a large variety of sensations not related to external stimuli. Taste and/or odor and thermal sensations were often reported as well as changes in auditory or visual perception of the environment in addition to reports of general heaviness, relaxation or tingling. PMID- 2097908 TI - Arterial oxygen saturation in children receiving rectal midazolam as premedication for oral surgical procedures. AB - Eighty healthy children, between the ages of 2 and 7 years, undergoing dental procedures were monitored with a pulse oximeter for changes in arterial oxygen saturation. The children were randomly allocated into 4 groups in this double blind study. Three groups received rectal midazolam, and the other group a placebo (saline) as premedication 30 min prior to induction of anesthesia. Group A children received midazolam 0.25 mg/kg, Group B 0.35 mg/kg and Group C 0.45 mg/kg. The results from this trial show no statistical significant difference between the treatment groups as to the effect on either systolic or diastolic blood pressure, respiration, or pulse rates at either pre- or post-sedation levels. However, the oxygen saturation levels for groups B and C differed significantly from those of the placebo groups 30 minutes after premedication (P = 0.0259). PMID- 2097909 TI - An analysis of the effectiveness of two topical anesthetics. AB - This study compared the effectiveness of topical benzocaine 20%, lidocaine 5%, and a placebo in reducing the pain caused by needle insertion when the medicament was placed in the mucobuccal fold above the maxillary canine eminence. Both topical anesthetics and the placebo were randomly tested against each other bilaterally. For uniformity the agents were left in place for three minutes before needle insertion. A 27 gauge short needle mounted on an aspirating syringe was then inserted just past the bevel. Each subject rated the degree of pain on a visual analogue scale 100 mm in length. A pulse oximeter was used to record the heart rate. The results indicate that both topical anesthetics are significantly better than the placebo in reducing pain caused by needle insertion, although no statistically significant differences were found between the two topical anesthetics. Statistically significant differences in heart rate were seen, but these differences were not clinically significant. It is concluded that benzocaine 20% and lidocaine 5% significantly reduce the pain during needle insertion. PMID- 2097910 TI - Periodontal ligament injection: alternative solutions. AB - This study was undertaken to investigate whether plain lidocaine, 3% plain mepivacaine and 3% prilocaine with felypressin were suitable epinephrine-free local anesthetic solutions for use in periodontal ligament anesthesia as alternatives to lidocaine with 1:80,000 epinephrine. Two hundred and seven patients received one of the four test solutions via a periodontal ligament injection and the success rate of anesthesia was confirmed using an electric pulp stimulator. Although neither mepivacaine nor prilocaine were as effective as lidocaine with epinephrine, the success rates of these three solutions were not statistically different. A single periodontal ligament injection of any of the solutions tested resulted in a low incidence of anesthesia. The success rate of lidocaine without epinephrine was consistently poor. PMID- 2097911 TI - Submental administration of succinylcholine in children. AB - During inhalation induction of the pediatric patient, laryngospasm can develop before intravenous access has been established. The intramuscular administration of succinylcholine is commonly used in such instances. This study was designed to determine if the injection of succinylcholine by an extraoral submental approach would be an acceptable method of terminating laryngospasm when compared to conventional intramuscular sites. Following induction with halothane and nitrous oxide in oxygen, a total of fifteen ASA 1 children were given 3.0 mg/kg intramuscular succinylcholine either intralingually by a submental approach, or using the upper leg musculature in order to electromyographically measure the time to maximum (or 90 percent depression from baseline) twitch depression. The intralingual submental injection had a mean twitch depression of 265 +/- 62.5 seconds compared to the quadriceps femoris at 295 +/- 42.6 seconds. A group with digital massage of the intralingual injection site produced a mean depression time of 133 +/- 11.9 seconds and was also the only group providing 100% success rate in reaching the desired twitch depression level. This may suggest that the operator should consider digital massage to produce a more predictable and desirable result. PMID- 2097912 TI - Dental anesthesiology training at the University of Toronto--30 years later. PMID- 2097913 TI - Structural studies on allergen RC-13 from Ricinus communis L.: isolation and characterization of a major glycopeptide. AB - A glycoprotein, RC-13, isolated from Ricinus communis seeds was reduced, S alkylated and cleaved by trypsin. The tryptic digest was fractionated by ion exchange chromatography and a glycopeptide was isolated and purified by high voltage paper electrophoresis. When submitted to amino acid and carbohydrate analyses this major glycopeptide showed the following chemical composition: Lys1, Asp1, Thr2, Ser4, Glu1, Pro2, Gly2, Ala2, Val2, GlcN6, Man6 and Gal8. Hydrazynolysis positioned Ser as the C-terminal residue. It is postulated that this glycopeptide belongs to the C-terminal region of the allergen. PMID- 2097914 TI - Development of the coronary arteries in staged human embryos (the Paris Embryological Collection revisited). AB - Twenty seven human embryos from stages 15 to 23 (postsomitic period), belonging to the collection of the "UFR Biomedicale des Saints-Peres, Universite Rene Descartes Paris V", were studied. Details of the aorticopulmonary cleavage were analysed specially aortic valve development and origin of the coronary artery. At stage 18 the aortic valve was clearly distinguished (cup-shaped) presenting semilunar valves and aortic sinus (Valsalvae); at this stage the left coronary artery was detected in 66.7 per cent of the cases as an endothelial epicardial invagination. At stage 19, the left and right coronary arteries were detected simultaneously in 100 per cent of the cases. At stage 20, the coronary arteries showed greater structural complexity with a coat of mesenchymal cells. These results agree with previous data from different embryological collections. These findings suggest that the left coronary artery has a tendency to develop earlier than the right. We found no evidence of the coronary origin from the aortic lumen. This work provides additional information about the embryological development of the heart, obtained from the analyses of a French collection of human embryos. PMID- 2097915 TI - [Life style, environment and childhood diseases]. PMID- 2097916 TI - [Analysis of the human genome in pediatric hemato-oncology]. PMID- 2097917 TI - [Genetics of metabolic diseases. Including cystic fibrosis]. PMID- 2097918 TI - [Molecular aspects of hereditary growth hormone defects]. PMID- 2097919 TI - [Pediatric AIDS in Spain]. PMID- 2097920 TI - Child health as a world problem. PMID- 2097921 TI - [Physiology of puberty]. PMID- 2097922 TI - [Normal puberal development. Clinical stages. Evaluation]. PMID- 2097923 TI - [Infantilism and puberal retardation of gonadal origin]. PMID- 2097924 TI - [Hypogonadotropic hypogonadism]. PMID- 2097925 TI - [Infantilism of non-endocrine origin]. PMID- 2097926 TI - [Treatment of sexual infantilism]. PMID- 2097927 TI - [The study of the human genome in pediatrics today]. AB - The author studies the present of genetic diseases, its great importance in the modern pediatrics and the main basic concepts. Also he reviews gene's function and constitution, DNA probes genoma, genetic code, gene mapping and others current problems in genetics: diagnostic applications, infectious diseases, prevention of inherited diseases, genetic counseling, prenatal sex determination by DNA probes, cell gene therapy and finally the ethical issues. PMID- 2097928 TI - [Diagnostic methodology of genome alteration]. AB - Advances in molecular biology have produced great results concerning with the knowledge about hereditary mechanisms and gene diseases. In the last twenty years the development of discoveries have exceeded the information of clinical pediatricians, and the technology of genetic engineering, evolved from the properties of the DNA molecule, give us powerful diagnostic tools much more specific than those of classical cytogenetics limited to gross disorders of cariotype. Cellular cultures, autoradiography and electrophoresis have been very useful to develop molecular genetics. Using hybridomas a gene can be located into one chromosome. After wards the restriction map may be represented and employed as routine diagnostic procedure. Final objective is the genetic map with the complete sequence of normal and abnormal genes. To do so, more sophisticated methods are coming that still belong to the field of research. PMID- 2097929 TI - [Molecular analysis in hereditary neuromuscular diseases]. PMID- 2097930 TI - [Ecoepidemiology of leishmaniasis in Syria. 1. Leishmania major Yakimoff and Schokhor (Kinetoplastida-Trypanosomatidae) infestation of Psammomys obesus Cretzschmar (Rodentia-Gerbillidae)]. AB - During an epidemiological survey of zoonotic cutaneous leishmaniasis in South West Syria, Leishmania major zymodeme MON-26 was isolated from a reservoir host, Psammomys obesus terraesanctae (Rodentia-Gerbillidae). The abundance of this rodent, its close contact with infected villages and the high prevalence of the infection (63,1%) indicate that this is the main reservoir host of oriental sore in the semi desert area of this country. PMID- 2097931 TI - Acute chagasic cardiopathy produced by a strain of Trypanosoma cruzi (type I) in an experimental model. AB - We have carried out a study of the tissular tropism of the strain Y of T. cruzi considering that the different strains of T. cruzi show a great instability in their pathogenic properties with the aim of proving that the classifications of his parasite based in its tissular tropism are not reliable given that these characteristics are subject to change as can be seen by comparing our results with those of other authors. In our study, the Y. strain of T. cruzi shows a strong pancytotropic action, specially with marked cardiotropic aspects. The lack of affectation in the lymphatic ganglion and the small proportion of spleen lesions (8%) as well as the absence of pseudocysts at this level is surprising in a strain which was described as eminently reticulotropic. Our data show that this strain produces cardiac pseudocysts without lesions of the parasitized muscle fiber. The above mentioned data evidence that the biological behavior of a strain and specially its tissular tropism are susceptible to present variations with time. PMID- 2097932 TI - Reproductive anatomy and gametogenesis in Shipleya inermis (Cestoda: Dioecocestidae). AB - Study of the reproductive anatomy in 65 strobilae of the dioecious cestode Shipleya inermis Fuhrmann, 1908 (Acoleata: Dioecocestidae) showed that a common genital duct, probably arising through fusion of the vas deferens and the proximal portion of the vaginal duct, compensated functionally for the loss of a patent vagina. Gonochorism was characteristic, but rudimentary genital organs of the opposite sex were present in 26% of males and 9% of females; two strobilae (3%) were hermaphroditic. Hermaphrodites had normally developed male organs and were capable of cross-fertilization as males; their female organs were much reduced in size but were functional, and eggs or fertilized ova in the uteri indicated that self-fertilization occurred. Gametogenesis was traced, mainly in chromosomal preparations. The diploid chromosomal complement in embryos and germ line cells consisted of four pairs of homologues (2n = 8, n = 4, FN = 14). Based on observation in female cestodes of one pair of chromosomes having non homologous or non-pairing segments due to influence of heterochromatin, the authors suggest that females produce gametes of two types relative to heterochromatic DNA, while males are homogametic, and that sex-determining effects are associated therein. In males, meiosis included chromosomal pairing and recombination, after which heterochromatin was eliminated from germline cells through fragmentation. Other biological characteristics of S. inermis in the hosts, Limodromus spp. (Charadriiformes), are briefly discussed. PMID- 2097933 TI - Rabbits infested with Ixodes ricinus L. adults: effects of a treatment with cyclosporin A on the biology of ticks fed on naive and immune hosts. AB - Rabbits have been infested 3 times with 10 female and 10 male Ixodes ricinus. Immunity which is induced when ticks feed on naive animals (1st infestation) perturbs feeding, oviposition and embryogenesis during reinfestations. Treatment of rabbits during a 3rd infestation (resistant animals) with cyclosporin A (CsA), an immunosuppressive agent which works on the cellular compartment (chiefly T helper cells), partially reversed the negative effects of the immunity on the biology of the ticks. Conversely, CsA may also directly affect the reproductive processes of ticks. Thus, the weight of the eggs laid and the egg conversion factor of ticks fed on naive treated hosts (1st infestation) were diminished. In addition, the preoviposition was prolonged, and finally failure in oviposition and hatching occurred more frequently. PMID- 2097934 TI - Cutaneous leishmaniasis of man due to Leishmania (Viannia) naiffi Lainson and Shaw, 1989. AB - Until recently mammalian hosts of Leishmania (Viannia) naiffi Lainson & Shaw, 1989 have been limited to armadillos, Dasypus novemcinctus, in Amazonian Brazil. Past evidence for human cutaneous leishmaniasis due to this parasite is reviewed, and a recent infection in man reported, with identification of the parasite by isoenzyme profiles and a specific monoclonal antibody. The role of some phlebotomine sandfly species as vectors is discussed. PMID- 2097935 TI - [Use of composites (1)]. PMID- 2097936 TI - [Laser in periodontology: theoretical-experimental approach. 1. The laser system: definition, function, classification]. PMID- 2097937 TI - [Action of the Delaire facial mask: a clinical case]. AB - Authors describe the effects of face mask therapy in III class treatment. A case report is presented. PMID- 2097938 TI - [Myxoma of the oro-maxillo-facial region]. PMID- 2097939 TI - [Comparative analysis of materials for dentino-pulp protection: varnishes, liners, ZOE cements, zinc oxyphosphate cements, zinc polycarboxylate cements, calcium hydroxide cements]. AB - The Authors review the principal materials used for pulp and dentine protection. Them they examine the main characteristics of each materials about different clinical situations. PMID- 2097940 TI - [Respiratory and deglutition pathology in malocclusion]. AB - The Authors, in this work, describe the ripercussions fixed by the pathology of the first respiratory organs and of the deglutition both at expense of maxillo facial development and at systematic-level; by beginning from physiologic mechanisms, the most frequent causes of the oral respiration and the atypic deglutition are analysed. PMID- 2097941 TI - [Case of rapidly progressing periodontitis. Clinical evaluation after three years]. PMID- 2097942 TI - [Laser in periodontology: theoretical-experimental approach. 2. The laser and biostimulation: hypothesis of the physico-biological mechanism of action]. AB - The Authors describe the physical principles regulating interaction between laser beam and living matter. Then they review the biological assumptions that explain the clinical effects on latest experimental data. PMID- 2097944 TI - [Myxoma of the mandible. Clinical case]. PMID- 2097943 TI - [Esthetic facial deformities and their psychosocial implications]. PMID- 2097945 TI - [Proposed use of natural teeth for management of a prosthetic case]. AB - Authors describe the case of a periodontopathic patient having seriously involved lower incisors. They used a splinting system consisting of a lingual metal bar using close healthy teeth as an anchor, and using previously extracted teeth of the patient to get a good aesthetical, psychological and functional result. PMID- 2097946 TI - [Laser in periodontology: theoretical-experimental approach. 3. Experimental study of the effects of He-Ne (638 nm) and infrared diodic (904 nm) lasers on the gingival mucosa of rats]. AB - Medical and surgical laser-therapy is becoming more and more important in various branches of Medicine, however independently from clinical results still very little is known about physical-biological interaction between laser beam and living matter. The aim of this study is of finding tissutal and cellular effects of stimulation with soft and mid laser. The study started from an original work carried out at the Institute of Biology of the 1st Faculty of Medicine and Surgery of Naples University from which appears the possibility of visualizing the stage of nuclear active synthesis of the cell, simply by Maloory tricromic colouring. By this method the cellular nucleuses take, usually, a red colour, however in presence of an increase of the RNA nuclear synthesis the nucleuses take a typical blue colour. The importance of the study induced us to research the presence in the oral mucose of the rat after radiation as an effect of biostimulation. The results of this study showed and increase of the epithelial cheratine and a variation of the disposition and of the number of the precheratine grains in treated site. The blue nucleuses have been found at the basal level without any difference between treated and control site. On the other hand their presence is the normal consequence of the epithelial evolution which starts from the basal level which is the most active in the stage of nuclear synthesis. PMID- 2097947 TI - [Relationship between orthodontic treatment and TMJ pathology: current knowledge]. AB - The Authors examine the international literature about the relationship between orthodontics and TMJ status. In five articles cited, the TMJ status who had received orthodontic treatment was compared with controls and no major differences was noted. PMID- 2097948 TI - [Water absorption by denture base resins]. AB - In a review of the international literature about water absorption of denture base resins any effect on the physical properties of these polymers has been considered. The authors discuss the possibilities of controlling the final results on denture base function. PMID- 2097949 TI - [Nonsteroidal anti-inflammatory drugs in therapy of periodontal disease]. PMID- 2097950 TI - [Hallermann-Streiff-Francois syndrome]. AB - Hallermann-Streiff-Francois Syndrome, or oculomandibulodyscephaly is a rare congenital anomaly, characterized by bilateral congenital cataracts and bird face. As the disease always involves oral troubles, that sometimes precede or predominate over other symptoms, the patient need oral examinations and life-long rehabilitation. PMID- 2097951 TI - [Drug-induced hypertrophic gingivitis. Presentation of two clinical cases]. PMID- 2097952 TI - [Mandibulofacial dysostosis or Treacher-Collins syndrome: clinical case]. PMID- 2097953 TI - [Orthodontic movement and root resorption]. AB - Frequent sequela following orthodontic treatment is some degree of root resorption. Much controversy exists concerning its cause and predisposing factors. The purpose of this study was a review of the literature. PMID- 2097954 TI - [Particular form of hemifacial microsomia: clinical case]. PMID- 2097955 TI - [Effects of chronic allergic rhinitis on dental and skeletal development]. PMID- 2097956 TI - [Open bite: classification and etiopathogenetic examination]. AB - In the present study different types of "open-bite" have been taken under consideration. First of all, have been analysed the main etiopathogenetic factors which are the causes of the malformation in sphere of various classifications. PMID- 2097957 TI - [Nonodontogenic facial pain of dental significance]. AB - The authors review the main facial pain syndromes, which put often important diagnostic problems to the chephalic district specialists. The syndromes are discussed with modern nosographic criteria. Epidemiologic data and pain peculiarities, both essentials for a correct diagnosis, are stressed for each of the reported syndromes. PMID- 2097960 TI - [Morphology of the cranial base in a group of Campania school children]. AB - The A.A. analysed the cranial base morphology on 14 school-children in the eastern part of Naples, to establish if the most used cephalometric values were useful for Campanian people. The values found out resulted superimposed to those referred in the considered analysis. PMID- 2097961 TI - [Gardner's syndrome]. AB - The Gardner syndrome is characterized by polyposis coli and multiple hard and soft tissue tumors. This work show crucial dentist's role in the early diagnosis important for the highly malignant potential of this syndrome. PMID- 2097958 TI - [Use of composites (2)]. PMID- 2097959 TI - [Clinical suggestions on the use of calcium hydroxide in therapy of pulp necrosis]. AB - The Aa. discuss the Bernard's method for therapy of pulpar necrosis, based on using of calcium oxide, know as "ocalexic method". They report clinical procedure and results of their experience. PMID- 2097962 TI - [Dens invaginatus]. PMID- 2097963 TI - [Experimental verification of the content of premeasured capsules of four different dental amalgams]. AB - The Authors examine the problem of exactness of measure of weight in amalgam capsules and precision of ratio metallic powder-mercury. They study four materials and in some cases they found big want of precisione in dosing of capsules. PMID- 2097964 TI - [Water absorption by composite resins]. AB - A literature review about water absorption in dental composites has led to a number of hypotheses made for the variables affecting the experimental behaviour. It follows a discussion about the possible advantages and disadvantages of the fenomenon. PMID- 2097965 TI - [Surgical-orthodontic disimpaction of an upper central incisor. Clinical case]. PMID- 2097966 TI - [Incipient carious lesions in patients undergoing fixed orthodontic treatment: a proposed specific prevention plan]. PMID- 2097967 TI - [Importance of the study of cephalometric values in a patient with Melnick Needles syndrome (clinical case)]. AB - The Authors exposed cephalometric analysis in a patient with Melnick and Needles syndrome. Craniomaxillary, maxillofacial, dentomaxillary, skeleton and soft tissue spatial ratio have been evalued. PMID- 2097968 TI - [Progressive systemic sclerosis (scleroderma): oral manifestations]. PMID- 2097970 TI - [Head posture in orthodontics]. PMID- 2097969 TI - [Regeneration of old gutta-percha cones]. AB - Aged gutta-percha filling cones become brittle and unsuitable for use; a technique was published for reducing their fragility, thus "rejuvenating" them. The Authors study this technique in five different cone brands, but only 30% of cones made usable. PMID- 2097971 TI - [Emergency situations in ambulatory dentistry. 2. Execution technique of therapeutic measures]. PMID- 2097972 TI - [Etiological problems of anterior tooth crowding: the role of the third molar]. AB - The authors discussed about the extraction or not of the 3 degrees molar either to prevent or correct the dental crowding. They state that, since there is no definitive evidence of the real importance of the 3 degrees molar in creating dental crowding, it is not possible to perform without discrimination 3 degrees molar germectomy nor the extraction for prevention. PMID- 2097973 TI - [Choice of restorative materials in posterior Class V cavities]. AB - Microleakage of class V restorations in posterior teeth was studied, using different types of materials and cavity varnish. Significantly less microleakage was recorded by applying some layers of cavity varnish and using spherical alloy. PMID- 2097974 TI - [Hutchinson-Gilford syndrome]. PMID- 2097975 TI - [Teratomas of the facial mass]. AB - The A. after bringing up to date the bibliografic dates about the subject, describes the cases T of maxillo-facial district reported by the literature. Subsequently, he illustrates the most recent classifications and etiopathogenic and anatomic-pathologic theories formulated on these neoformations. PMID- 2097976 TI - [Caffey's disease]. AB - Caffey's disease or infantile cortical hyperostosis a rare condition affecting infants in the first five months of life. The disease begins usually as an acute febrile illness accompanied by painful swellings over one or more bones, with all the signs of acute inflammation. PMID- 2097977 TI - [Tooth transposition: current knowledge]. PMID- 2097978 TI - [Etiopathogentic aspects, clinical picture and differential diagnostic view of first and second branchial arch syndromes]. AB - The AA. examine in the present work the main syndrome of I and II branchial arch, valuing the hetiopathogenetic and clinic aspects and determining a diagnostic differential scheme between the same. It is underlined the importance of the echografic exam for the prenative diagnosis and the clinic exam for the after native diagnosis. PMID- 2097980 TI - [Lateral facial clefts: surgical technique]. PMID- 2097979 TI - [Cementoblastoma and nosological problems]. PMID- 2097981 TI - [Cephalometry of cleft lip and palate]. AB - This study demonstrated that there were basic differences in facial morphology between patients with cleft lip and palate and subjects with non clefting. The findings are obtained on cephalometric analysis of skull's teleradiograph L-L. These differences are for all pratical purposes confined to the maxillary complex. The mandible appear, instead, normal unless in the position in every respect in the not cleft lip and palate subjects. PMID- 2097982 TI - [Parry-Romberg syndrome]. PMID- 2097983 TI - [Clinical case of "dens invaginatus"]. PMID- 2097984 TI - [Diseases of ancient Egyptian mummies]. PMID- 2097985 TI - 2nd International Symposium on Molecular Genetics of Diabetes Mellitus. April 23 25, 1990, Greifswald. PMID- 2097987 TI - Expression of the growth hormone receptor gene in insulin producing cells. AB - Growth hormone (GH) plays a dual role in glucose homeostasis. On the one hand, it exerts an insulin antagonistic effect on the peripheral tissue, on the other hand, it stimulates insulin biosynthesis and beta-cell proliferation. The expression of GH-receptors on the rat insulinoma cell line RIN-5AH-T2-clone B was studied. The binding characteristics with regard to specificity for the native 22 kDa hGH, and the 20 kDa variant were similar to that reported on rat adipocytes. Normal rat islet cells showed a similar affinity for hGH. The RIN cells express GH receptors similar to the cloned liver receptor. It is hypothesized that defects in the receptor expression on the beta-cells may contribute to the susceptibility to develop diabetes. PMID- 2097986 TI - Hormone genes, structure and control of expression. PMID- 2097988 TI - Liposome mediated in vitro transfection of pancreatic islet cells. AB - The aim of this study was to evaluate the suitability of the liposome technique for transfection of pancreatic islet cells in vitro. For this purpose, fetal islets were isolated and cultured free floating for two days after which they were further cultured, either intact or dispersed into islet cell suspensions, with different DNA-liposome preparations. The DNA-construct used were the control plasmid (pSP65) and the viral oncogene v-src contained in the plasmid pSPRIsrc. A previous study showed that islet cells transfected by means of electroporation with pSPRIsrc displayed an increased thymidine incorporation rate, making this plasmid suitable for further transfection studies. The DNA was associated with the liposomes by means of surface adhesion. The liposomes used were either conventional phosphatidylcholine-containing liposomes, phosphatidylethanolamine/oleic acid containing liposomes (pH-sensitive liposomes) or Lipofectin. After the exposure of islet cells to the DNA-liposome preparations, the transfection efficiency was assessed by determination of the uptake of the DNA-constructs (Southern blot analysis) and expression of the gene construct into an mRNA (Northern blot analysis). In addition, the impact of the different DNA-liposome preparations on islet DNA replication (thymidine incorporation rates) was determined. It was found that two days after exposure to the DNA-liposomes, the v-src construct was located in islet cell nuclei and that v-src derived transcripts were transiently expressed in the islet cells. The Lipofectin liposomes were more efficient in transfecting islet cells than the pH sensitive liposomes as assessed by the blotting techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2097989 TI - Expression of the insulin gene is regulated by opioid peptides. AB - The effects of the opioid peptides Met- and Leu-enkephalin on the expression of the insulin gene in isolated adult rat islets of Langerhans were examined. Isolated rat islets were maintained under various culture conditions for 26 h. The contents of islet preproinsulin mRNA and the amounts of (pro)insulin biosynthesis were assayed. In the presence of 5 mM glucose the preproinsulin mRNA content was increased by 10(-8) M Met-enkephalin to 198% (p less than 0.001) and by Leu-enkephalin to 145% (p less than 0.001) of the control without enkephalins. The preproinsulin mRNA content was raised in the presence of 5 mM glucose by 10( 10) M significant. These results corresponded with an increase in the (pro)insulin biosynthesis under the same conditions. The biosynthesis of (pro)insulin was strongly decreased by actinomycin D at the glucose and enkephalin concentrations tested. The results demonstrated that there is a dose dependent stimulation of the insulin gene expression by enkephalins and that the increase in (pro)insulin biosynthesis in isolated pancreatic islets by endogenous opioid peptides occurs mainly on the pretranslational level. PMID- 2097990 TI - In vitro transcription of the human insulin gene. AB - Insulin gene transcription is a highly tissue specific process which only takes place in the pancreatic beta-cell, and may be explained by the interaction of a unique composition of transacting factors and insulin gene 5' enhancer/promoter elements. In order to study differences in transcription factors from either insulin or non insulin producing cell lines we have developed an in vitro transcription assay of the human insulin gene. Efficient transcription was obtained using nuclear extracts from insulin as well as non insulin producing cell lines, and we were so far not able to mimic in vivo conditions present in beta-cells. The method is now routinely being used to test the activity of nuclear extracts before they are used in other analyses such as gel retardation assays and footprinting experiments. PMID- 2097991 TI - Genetic manipulation of rat hepatocytes in vivo. Implications for a therapy model of type-1 diabetes. AB - The successful expression of transferred insulin genes in non-pancreatic somatic cells could be an important step towards a somatic gene therapy of type-1 diabetes. Hepatocytes are potential target sites of a genetic manipulation. Using liposomes as a gene carrier system a method was established to manipulate rat hepatocytes in vivo. To prove this model, a bacterial marker gene (pRSVneo) was used which is normally absent in the mammalian genome. The genetic material was encapsulated into reverse-phase evaporated vesicles (REV). Using a sonication step for 60-90 s during vesicle preparation no significant loss of genetic information was observed. 70% of the liposomes were taken up by the liver within 10 min after i.v. application to male Wistar rats (1.5 mumol lipid and 10-15 micrograms DNA per 100 g b.w.). The transferred vector was detected in isolated nuclei of hepatocytes by Southern hybridisation up to 7 days. Integration events into the host genome were observed already 48 h after injection. The transcription of the transferred DNA (mRNA) as well as the translation (NPT-II activity) were demonstrated. PMID- 2097992 TI - Different mammalian facilitative glucose transporters expressed in Xenopus oocytes. AB - Xenopus oocytes exhibit an extremely low basal glucose transport and are thus ideally suited for the expression of heterologous glucose transporters. They have, therefore, proven to be a very valuable expression system to functionally express the erythrocyte/brain (GLUT1), the liver (GLUT2), and the adipocyte/muscle (GLUT4) glucose transporters. Characterization of their functional properties indicates that they fulfill the criteria of a glucose transport protein by demonstrating saturation kinetics, stereospecificity, and inhibition by cytochalasin B. Although mammalian facilitative glucose transporters have been expressed in bacteria and eukaryotic cell lines, the present data emphasize the advantage of using Xenopus oocytes for comparative kinetic analysis of the various members of the facilitated diffusion glucose transporter gene family. PMID- 2097993 TI - Transgenic animals in diabetes research. PMID- 2097994 TI - HLA-DQA1 and HLA-DQB1 DNA typing in multiplex IDDM families by use of sequence specific oligonucleotide probes and genomic sequencing. PMID- 2097995 TI - Complement component 3 (C3) genetics and diabetes mellitus. AB - Complement component 3 (C3) phenotype and allele frequencies were defined in 312 patients with type-1 diabetes (insulin-dependent diabetes mellitus), 256 patients with type-2 diabetes (non-insulin-dependent diabetes mellitus), 114 apparently non-diabetic first-degree relatives of type-1 diabetics, in 10 families (29 members) with a familial history of type-1 or type-2 diabetes, in 181 patients with coronary heart disease and 255 subjects with arterial hypertension. 512 blood donors served as controls. All persons investigated were Europeans. There is no evidence that genes linked to C3 influence susceptibility to type-1 and type-2 diabetes and to their late complications as well as to atherosclerosis and essential hypertension. The distribution of apolipoprotein E phenotypes in patients and controls was likewise not significantly different. The combined evaluation of data from linked genes (C3 and apo E) could not improve the results. Deductions of C3 as a genetic disease marker have to be interpreted with caution. PMID- 2097996 TI - Advances in measurement of reporter genes: chloramphenicol-acetyl-transferase and firefly luciferase. PMID- 2097997 TI - Reflex sympathetic dystrophy: a review. AB - Reflex sympathetic dystrophy is a unique traumatic disorder with unusual cutaneous signs. The case of a patient with an uncommon, poorly understood, sharply marginated geometric zone of erythema is reported. Pseudo-Kaposi's sarcoma developed in the same patient in the foot affected by reflex sympathetic dystrophy, an association not previously reported. For effective treatment this disorder must be diagnosed as early as possible. The clinical stages of evolution through which reflex sympathetic dystrophy progresses are described. PMID- 2097998 TI - Management of alarming hemangiomas in infancy: a review of 25 cases. AB - During the past 10 years, 25 infants with alarming hemangiomas--lesions that impaired important functions and were life threatening, especially when there was visceral involvement--have been treated. A vascular mark was present at birth in 68% of these infants. Visceral hemangiomas were associated with bulky cervicocephalic hemangiomas or with small hemangiomas scattered over the body. Among the 25 infants, 12 had laryngeal hemangiomas, 3 had hepatic hemangiomas, and 1 had gastrointestinal hemangiomatosis. Ocular sequelae, malocclusion, and cutaneous distortion were the most important functional problems. Corticosteroid treatment was used for 23 of 25 infants with alarming hemangiomas. There was a varied treatment response: total failure (30% of the patients); excellent, dramatic, rapid improvement (30% of the patients); and moderate, doubtful response, with the natural course of the disease remaining unaltered (40% of the infants). Arterial embolization, used in 6 infants, gave inconstant results. Cardiac failure, frequently associated with large cutaneous hemangiomas and always seen with hepatic multinodular hemangiomas, required digitalization. In some cases arterial embolization reduced the increased cardiac output. Liver hemangiomas had a high mortality; all 3 infants with hepatic involvement died. PMID- 2097999 TI - Loculated hemopneumothorax of a major fissure in patients with COPD and associated pleural disease. AB - Two patients with underlying COPD and bullous changes of the lungs were found to have a loculated hemopneumothorax within a major fissure by computed tomography. Both patients had associated pleural disease. In one of the patients, the hemopneumothorax was believed to be potentially compromising pulmonary function. Percutaneous needle drainage of the loculated hemopneumothoraces resulted in large symptomatic pneumothoraces requiring urgent insertion of closed thoracostomy tubes. Loculated hemopneumothorax is an unusual finding within a major fissure mimicking pulmonary abscess, infected bullae, pulmonary cyst, or a cavitary carcinoma of the lung. Physicians treating patients with COPD and associated pleural disease should be aware of this rare condition, since percutaneous needle drainage may be associated with serious life-threatening complications. PMID- 2098000 TI - Movement disorders in alcoholism: a review. AB - A wide variety of movement disorders are associated with alcohol abuse. Some idiopathic movement disorders are markedly improved by small amounts of alcohol and this response occasionally may lead to alcoholism. Alcohol abuse alone or combined with hepatic encephalopathy can cause various types of tremor, asterixis, and cerebellar dysfunction. Alcohol withdrawal is occasionally complicated by transient basal ganglia dysfunction manifested by parkinsonism or chorea. These syndromes are distinct from the movement disorders complicating acquired hepatolenticular degeneration occurring in some chronic alcoholics. This review discusses the clinical and pathophysiologic aspects of the movement disorder syndromes that complicate alcohol abuse. PMID- 2098001 TI - Mother-infant interaction in a multirisk population. AB - The relationship among maternal and observer ratings of infant temperament, observer ratings of maternal responsiveness, and maternal drug abuse habits, was studied in a population facing multiple risk factors. Intensity of maternal drug abuse was found to be negatively related to maternal ratings of infant temperament, and ratings of temperament were positively related to maternal responsiveness. Implications for research and practice are explored. PMID- 2098002 TI - Concentrated morphine sulfate injection. PMID- 2098003 TI - Stress and coping of parents of children in a pediatric intensive care unit. AB - Knowing what parents find stressful about having a child in a pediatric intensive care unit and how they cope is essential before professionals can bolster their coping and provide support. In a semistructured interview we asked parents to discuss the aspects of the situation that they found stressful and to identify their predominant stressor. Then, using the Ways of Coping Questionnaire, we asked them to identify what coping strategies they used to cope with that predominant stressor. The questionnaire is designed to measure whether the strategies used are focused on the problem (situation) or on emotions engendered by the stressor or on both. Data on selected demographic characteristics of the family also were obtained. Fifty percent of the parent subjects identified stressors that were classified as loss of parenting role, 40% uncertainty over outcome, and 10% information need. Although the specific coping strategies used differed by the classification of stressors, all of the parents used a combination of both problem- and emotion-focused forms of coping. Seeking social support and positive reappraisal were the two most often used strategies by all parents regardless of the classification of stressors. No significant associations were found between stress or coping and any of the demographic variables. Research such as this can be useful to practicing clinicians who plan strategies that offer assistance and emotional support to parents of children hospitalized in the pediatric intensive care unit. PMID- 2098004 TI - Emergence of antibiotic-resistant bacteria during selective decontamination of the digestive tract. PMID- 2098005 TI - Histone H1 and the regulation of transcription of eukaryotic genes. AB - Histone H1 plays a role in the formation of chromatin structure, both at the level of the nucleosome particle itself and in the formation of the higher-order structures of the chromatin fibre. Histone H1 is regarded as a part of a general repressor mechanism that ensures a strong and stable repression of gene expression. In addition to serving as a general repressor for relatively large chromatin fragments, histone H1 might also be involved in controlling the transcriptional activity of individual genes. PMID- 2098006 TI - An outbreak of illness among aerospace workers. AB - A multispecialty panel of physicians evaluated a case series of 53 composite materials workers in a large aircraft manufacturing facility who filed workers' compensation claims for illness labeled by the media as the "aerospace syndrome." Possible skin and respiratory tract exposures included formaldehyde, phenol, particulates, epoxy resins, and trace organic solvents, but measured concentrations were well below all regulatory and consensus standards. Most workers had histories of transient skin or respiratory tract irritation consistent with the known potential toxicity of these materials. None of the workers tested had immunoglobulin IgG or IgE antibodies to human serum albumin complexed with formaldehyde. A majority (74%) met DSM-III-R [Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised] criteria for major depression, panic disorder, or both. Most of these psychiatric disorders were of a recent onset, correlating in time with the use of phenol- and formaldehyde impregnated composite material. Psychosocial factors were thought to have played a major role in the high prevalence of illness in this group and should be evaluated directly in well-controlled epidemiologic studies of similar crisis building situations in the future. PMID- 2098007 TI - Adverse cardiopulmonary effects and increased plasma thromboxane concentrations following the neutralization of heparin with protamine in awake sheep are infusion rate-dependent. AB - The effect of the rate of intravenous infusion of protamine on the acute hemodynamic and pulmonary effects of heparin neutralization was investigated in six adult sheep surgically instrumented for chronic studies. Bovine lung heparin at a dose of 200 IU/kg was injected intravenously over 10 sec, 5 min before the start of protamine administration. On separate experimental days, each sheep received protamine at the same dose of 2 mg/kg, but it was infused over four different time periods: 3 s, 30 s, 300 s, or 30 min. At an additional session, protamine was administered over 3 s without prior heparinization to assess the effect of protamine alone. The sequence of the sessions was randomized and performed blindly. Injecting protamine in unheparinized sheep produced no change in any of the measured variables. In contrast, when protamine was injected over 3 s in heparinized sheep, it induced a transient and significant (P less than 0.001) pulmonary hypertension (from 17.2 +/- 1.5 to 45.6 +/- 2.4 mmHg at 1 min) with an increased pulmonary (five-fold) and systemic (2.5-fold) vascular resistance; a decrease of cardiac output (from 3.85 +/- 0.43 to 1.93 +/- 0.29 l/min) without change in left atrial pressure (from 5.3 +/- 1.3 to 6.0 +/- 1.7 mmHg; P = NS); a significant (P less than 0.001) increase of plasma thromboxane B2 (TxB2) concentrations (from 349 +/- 131 to 974 +/- 218 pg/ml); leukopenia (76 +/- 4% of baseline white blood cell counts); and hypoxemia (PaO2 decreased from 81 +/- 3 to 63 +/- 4 mmHg at 2 min). Administering the same amount of protamine after heparin at a slower infusion rate significantly attenuated and delayed all components of the adverse response to protamine. This attenuation occurred in an infusion rate-dependent fashion, so that when protamine was infused over 30 min, no significant changes in any of the measured variables were noted. The time course of plasma heparin concentrations following protamine indicated that chemical heparin was completely neutralized over the time period of protamine infusion. These results demonstrate that the rate of generation of heparin protamine complexes (as detected by changes of plasma concentrations of chemical heparin) during iv protamine infusion started 5 min after heparin administration is a factor involved in the generation of sufficient mediators required to initiate a characteristic physiologic response in sheep, including systemic and pulmonary vasoconstriction, TxB2 generation, and leukopenia. Infusing a neutralizing dose of protamine over 30 min avoids these adverse reactions in sheep. PMID- 2098008 TI - Ethics and communication. PMID- 2098009 TI - A critical look at the subluxation hypothesis. PMID- 2098010 TI - Screening and breast cancer incidence. PMID- 2098011 TI - Prosthodontics. Research. Review of the literature. PMID- 2098012 TI - Bone density of elite female athletes with stress fractures. AB - To investigate whether stress fractures occurring in elite female athletes are related to reductions in bone mineral density (BMD), we measured BMD in nine athletes with such fractures and nine athletes without fractures who were matched for age, weight, height and sport. BMD was measured in three regions: upper limbs (distal radius), axial skeleton (lumbar spine) and lower limbs (femoral neck) by photon absorptiometry. The number of menses per year was significantly less (P less than 0.04) and the age of menarche was significantly delayed (mean +/- SD; 16.1 +/- 0.4 v. 14.4 +/- 1.5 years, P less than 0.02) in the fracture group compared with the non-fracture group. There was no significant difference in BMD between the two groups at any of the measurement sites. Moreover although the fractures occurred mainly in lower limb bones, at sites characterised by predominantly cortical bone, all athletes had femoral neck BMD values within the 95% confidence limits for normal non-athletic women. We conclude that stress fractures in elite female athletes are largely independent of BMD. PMID- 2098013 TI - Visual neglect during intracarotid amobarbital testing. AB - The unilateral suppression of hemispheric function by sodium amobarbital may result in hemispatial visual neglect, as measured by performance on a random letter cancellation task. Our study not only investigates this hypothesis but also attempts to identify more precisely the anatomic locus of control for directed attention to extrapersonal space by correlating scanning performance with EEG activity. Forty-eight consecutive patients with epilepsy underwent preoperative intracarotid amobarbital tests. The results indicated that disruption of scanning and contralateral neglect occurred only after right hemisphere suppression and seemed specifically related to changes in right frontal lobe EEG activity. This pattern of performance held not only for right handed subjects, but also for those who were left-handed, and even for those who had right-hemisphere language dominance. PMID- 2098014 TI - Psychosocial aspects of chronic, clinically unconfirmed vulvovaginitis. AB - Women with chronic symptoms of vulvovaginitis referred to a university vulvovaginitis clinic were assessed on psychological and social (including sexual) variables to determine whether differences existed among women with unconfirmed vulvovaginitis, women with confirmed vulvovaginitis, and healthy controls. Eighty-three consecutive women with chronic symptoms of vulvovaginitis and 32 asymptomatic control women completed clinical examinations, cultures, and the following psychological tests or questionnaires: the Brief Symptom Inventory, the Center for Epidemiologic Studies--Depression Scale, the Dyadic Adjustment Scale, a sexual behavior and response questionnaire (Campion), and a study questionnaire. Statistical analyses (chi 2 and analysis of variance) were performed on the confirmed and unconfirmed vulvovaginitis and control groups of women. Women with confirmed and unconfirmed vulvovaginitis scored higher than control women on several psychological variables, but women with unconfirmed vulvovaginitis were found to be significantly more emotionally distressed on psychological tests and to report more discomfort during sexual intercourse than both women with confirmed vulvovaginitis and healthy controls. Psychosocial inquiry is important in the clinical assessment and management of such women. PMID- 2098015 TI - Legal interventions during pregnancy. Court-ordered medical treatments and legal penalties for potentially harmful behavior by pregnant women. PMID- 2098016 TI - The value of immunotherapy with venom in children with allergy to insect stings. AB - BACKGROUND: The treatment of patients allergic to insect stings with insect-venom injections has been shown to be 97 percent effective in reducing the risk of sting-induced anaphylaxis. However, the frequency of systemic reactions to subsequent stings in unimmunized adults with previous reactions is approximately 60 percent. To determine which factors, in addition to a history of reaction and evidence of venom-specific IgE antibody, predispose patients to future insect sting reactions, we studied a venom-sensitive group of children who were deemed to be at relatively low risk for severe reactions; 28 percent of them received venom therapy. METHODS: We studied 242 children, 2 through 16 years of age, each of whom had had a systemic allergic reaction, affecting only the skin, to an insect sting. Each child had a positive skin-test reaction to one or more of five hymenopteran venoms. Sixty-eight children received immunotherapy with insect venom and 174 did not; about half were randomly assigned to treatment groups, and the rest were assigned on the basis of the patient's (or the parents') choice. The results of accidental stings during four years of observation were evaluated. RESULTS: In the treated group, 84 stings in 36 patients resulted in one systemic reaction (1.2 percent of stings). In contrast, 196 stings in 86 untreated children resulted in 18 systemic reactions (9.2 percent of stings, P less than 0.001). Sixteen of these 18 reactions were judged to be milder than the patient's reaction to the first sting, 2 were similar in severity, and none were more severe. CONCLUSIONS: These data confirm that immunotherapy with insect venom prevents recurrences of systemic reactions after subsequent insect stings. Because of the surprisingly low rate of reactions among untreated children, we could not identify any characteristics that were predictive of repeat reactions. Since only 9.2 percent of stings in the untreated children led to a systemic reaction and since there was no progression to a more severe reaction, we conclude that venom immunotherapy is unnecessary for most children who are allergic to insect stings. PMID- 2098017 TI - Cardiovascular depression after brachial plexus block in two diabetic patients with renal failure. PMID- 2098018 TI - Pediatrics 1990: facts and fantasies, myths and misconceptions. AB - Pediatrics is a constantly evolving medical specialty. As our knowledge grows through scientific research and careful observation, common pediatric concepts and practices are modified or sometimes even abandoned. Yet, for many reasons, clinicians tend to resist rapid changes and perpetuate antiquated practices, diagnostic strategies, and clinical policies. A number of such practices are presented along with the medical evidence supporting their discontinuation. PMID- 2098019 TI - Increased susceptibility of malaria-infected variant erythrocytes to the mononuclear phagocyte system. AB - The interactions of the mononuclear phagocyte system with Plasmodium falciparum infected genetically variant erythrocytes may result in a significant protection for the host. Infected hemoglobin (Hb) EE and Hb EA erythrocytes are more susceptible to phagocytosis by monocytes than are infected Hb AA erythrocytes. The increased susceptibility to phagocytosis of infected erythrocytes was also found for a number of genetic variants involving the alpha-globin chain, namely, alpha-thal 1 trait (--/alpha alpha), alpha-thal 2 trait (-alpha/alpha alpha), Hb H (--/-alpha), Hb H/Hb Constant Spring (CS) (--/alpha CS alpha), Hb CS trait, and homozygous Hb CS erythrocytes. In addition, oxidative damage from hydrogen peroxide, produced in simulation of macrophages, led to much more effective killing of parasites in glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes than in normal ones. Parasites infecting Hb H/Hb CS also showed an enhanced sensitivity to hydrogen peroxide. PMID- 2098020 TI - Enteritis in sheep, goats and pigs due to Yersinia pseudotuberculosis infection. AB - The features of naturally occurring Yersinia pseudotuberculosis serotype III infections in 16 sheep, one goat and 3 pigs, and Y. pseudotuberculosis serotype I infections in 3 goats, are described. Affected animals usually had diarrhoea and were in poor condition or emaciated. A number were moribund or dead when submitted for necropsy. Thickening of the caecal and colonic mucosa was the only gross lesion attributable to Y. pseudotuberculosis infection, with liver or other visceral abscesses not being seen. Characteristic microabscesses were demonstrated in the intestinal mucosa of 10 sheep, one goat and one pig infected with Y. pseudotuberculosis serotype III and one goat infected with Y. pseudotuberculosis serotype I. Sheep, goats and pigs dosed orally with Y. pseudotuberculosis serotype III, the serotype isolated most commonly from these species, developed intestinal infection. In sheep and pigs, infection was accompanied by diarrhoea. Haematological changes and specific antibodies were elicited in all 3 species in response to infection. Microabscesses were seen in the intestinal mucosa of all experimentally exposed animals. The occurrence of field cases and the results of experimental exposure confirm that Y. pseudotuberculosis serotype III is an enteropathogen of sheep, goats and pigs. The association of Y. pseudotuberculosis serotype I with lesions in a goat, indicates that this bacterium may also be a pathogen of this species. It is concluded that Y. pseudotuberculosis serotype III is an enteric pathogen of a wide range of ungulate species including cattle, buffalo, deer, antelopes, sheep, goats and pigs. Serotypes I and II, while having a more restricted host range, are probably also pathogens of ungulates and, in particular, deer, antelopes and goats. PMID- 2098021 TI - Delayed subarachnoid migration of an epidural catheter. PMID- 2098022 TI - Persistence of renal nerve and spinal reflex activities and visceral motility after asphyxial anoxia. AB - Phrenic and renal nerves activities, spinal reflex (knee jerk and the evoked monosynaptic reflex response from the 5th lumbar ventral root), motility of the stomach, duodenum, jejunum and colon, and motility of urinary bladder during and after the lethal asphyxia were studied in cats under intraperitoneal urethane (400 mg/kg) and chloralose (40 mg/kg) anesthesia. Asphyxial anoxia produced one or two peaks of elevation of systemic arterial pressure (SAP) followed by a progressive decrease of SAP and narrowing of pulse pressure and eventual complete cardiovascular arrest. The phrenic nerve activity increased markedly during the final asphyxial SAP elevation; it then decreased along with the decline of SAP and ceased permanently when the SAP reached about 50 mmHg. The renal nerve activity increased along with each phase of pressure elevation. During the terminal stage of progressive SAP fall, the renal nerve activity fluctuated up and down 2-3 times before the SAP dropped to zero, and the activity persisted for an average of 202 sec thereafter. Data suggest that the motoneurons of the phrenic nerve in the cervical spinal cord and medulla oblongata are more vulnerable to asphyxia than the motoneurons responsible for the spinal reflex in the pathway from medulla, the intermediolateral column of the spinal cord and the celiac ganglion. During anoxia, the lumbar spinal reflex showed an initial inhibition then potentiation afterward. Even after the SAP had reached zero, the spinal reflex could still be elicited for one to a few minutes. This suggests that the spinal cord can function sometime after complete cardiac arrest subsequent to asphyxia. The motility of the stomach, duodenum, jejunum, colon and urinary bladder usually decreased during the period of pressure elevation. However, the activity was enhanced during the terminal stage of pressure decline. The enhancement of the colon and bladder motility, spasmodic in nature, was particularly prominent, more so than the others. After complete cardiovascular arrest, the motility of the above viscera became temporary quiescent but about 10 minutes later, it resumed activity again with an enhancement of action in some of the animals. The motility, persisted from few minutes to over six hours. These phenomena indicate that despite a complete deprivation of circulatory and respiratory supports, or death of the animal, the viscera can still contract for a certain period of time. PMID- 2098023 TI - Congenital rubella in the Asian community in Britain. PMID- 2098025 TI - Consideration of drug load on the swelling kinetics of glassy gelatin matrices. AB - The effect of drug load on water transport into glassy gelatin beads and on the dynamic swelling behavior of the hydrated gel was studied through microscopic measurements of moving boundaries. Isoniazid was found to alter the glassy structure of gelatin, resulting in an increase in water penetration rates with a lowering of the apparent activation energy for water front movement. Differential scanning calorimetry studies revealed a decrease in the glass transition temperature with drug load, further indicating plasticization of the gelatin glass. The presence of drug also accelerated the outer swelling gelatin front, but, in contrast to the water front, the apparent activation energy for matrix expansion rose substantially with higher drug loads for temperatures greater than 20 degrees C. This observation may be rationalized as an increasing osmotic stress on the matrix induced by greater loading with hydrophilic drug. The osmotic stress, in turn, forces the gelatin matrix to expand outward, resulting in a higher apparent activation energy (Eact). Furthermore, the enhanced expansion was especially pronounced at higher temperatures where physical bonds, which are associated with gel structure and needed to resist swelling, are presumably weaker and fewer in number. PMID- 2098026 TI - Spreading depression marches on. PMID- 2098027 TI - Student selection. PMID- 2098028 TI - Vogt Koyanagi Harada disease. PMID- 2098029 TI - Neurocysticercosis. PMID- 2098030 TI - Feeding the compromised patient. PMID- 2098031 TI - Future for practice nurses. PMID- 2098032 TI - [Cytokines and their role as health and disease mediators. New approaches to old problems]. AB - The cytokines are multifunctional polypeptide hormones, produced by a variety of cells, that participate in the regulation of many biological processes. Essentially acting as intercellular messengers, they play a central role in the maintenance of homeostasis in normal tissues. Cytokines are key mediators of both local and systemic immune-inflammatory responses; therefore, disturbances in their secretion, response and/or regulation have been implicated in the pathophysiology of several conditions in which an exaggerated auto-destructive component appears to play a role. Conversely, deficits in cytokine production probably impair the host's ability to mount an effective immune response and may underlie the increased susceptibility to microbial infection observed, for example, in the neonate or in the malnourished patient. A review of the principal aspects of the biology of cytokines is presented together with the evidence supporting their involvement in several pathological states and the potential therapeutic applications of these mediators as novel immunomodulating agents. PMID- 2098033 TI - [Transient myocardial ischemia in newborn babies with perinatal asphyxia (hypoxic cardiomyopathy)]. AB - A prospective study in 76 newborn with perinatal asphyxia searching for myocardial ischemia was carried out. The disease was found in 51% of the patients. With electrocardiogram, myocardial enzymes, X ray and clinical manifestations the diagnosis was elaborated. No difference in the sex was present, the mean of gestational age was 35 weeks, and with mean birth weight 2,216 g, respiratory distress was present in all the people; only 20.5% developed heart failure and two had heart murmurs; 61.5% showed cardiomegaly. The creatine kinase MB isoenzyme at twelve hours after birth was raised in most of the patients. Respiratory distress syndrome was the principal diagnosis in 38%; hypoxic ischemic encephalopathy and peri-intraventricular hemorrhage was present in 50 and 33% of the patients, respectively. Mortality rate was 33%. Also a comparative study in the infants with and without myocardial ischemia was carried out appearing significative difference in: 1. Cardiomegaly, 2. Hypoxic-ischemic encephalopathy and 3. Creatine kinase MB isoenzyme. PMID- 2098034 TI - [Treatment of diarrhea and use of oral rehydration therapy in two socially different populations]. AB - A prospective, observational, transverse and comparative study was carried out using a survey in two socially different populations with the purpose of evaluating the way each population treats children with acute diarrhea. The study dealt with the following: nourishment of children with acute diarrhea, medications used and degree of know-how on the oral rehydration method. The results show that a part of the rural population as well as that of the urban sector, has incorrect concepts on nourishing a child with an acute diarrheal syndrome; that a high percentage of self-medicating occurs, caused in part by the health team, who serves as the main promoter of health concepts within the community. There is a need to improve educational concepts among the medical and paramedical personnel, in order to obtain a more efficient participation on behalf of community in the care of their own health. PMID- 2098035 TI - [Congenital malformations in live-born neonates]. AB - A retrospective study on the incidence and prevalence of congenital malformations in living newborns registered during a period of two years (1987-1988) at the University Hospital "Dr. Jose Eleuterio Gonzalez" in Monterrey, Nuevo Leon was conducted. The data was tabulated based on the classification codes established by the World Health Organization (WHO), grouped according to organs and systems and by sex. Of a total of 9,675 living newborns registered, 224 (2.31%) had a congenital malformation: 102 males, 121 females and one of undetermined sex. The greatest incidence corresponded to the central nervous system, following in descending order the cardiovascular and muscular-skeletal systems, cleft lip and palate, digestive system, genitalia, chromosomic anomalies, respiratory and urinary systems and congenital cataracts. The prevalence of congenital malformations in our population is similar to that reported in other countries with respect to neural tube defects. Muscular-skeletal and multiple malformations were less frequent than seen in other hospitals. PMID- 2098036 TI - [Variable angle strabismus and its relation to poor vision and psychomotor retardation]. AB - Variable angle strabismus can be inward (esotropy) or outward (exotropy) or vary from esotropy to exotropy. Mental retardation has been found to be related to strabismus in 50% or more of the cases and 35% of these had variable angle strabismus. A total of 61 patients with variable angle strabismus were studied finding 55.7% with esotropy, 36% exotropy and 8.2% varying from esotropy to exotropy. Of those under study, 64% were females and 77% under five years old. No accommodative factors were found in any of the patients. The best results were obtained through surgery (recession plus Faden) previous rehabilitation. PMID- 2098037 TI - [Frequency with which semiquantitative expressions are used in Mexican medical literature]. AB - OBJECTIVE: To describe the frequency with which semiquantitative expressions are used in Mexican medical journals. STUDY DESIGN: [corrected] Comparative survey. Frame of reference. Four Mexican medical journals considered representative of the medical literature in Mexico were studied (Revista de Investigacion Clinica, Archivos de Investigacion Medica, Revista Medica del IMSS and the Boletin Medico del Hospital Infantil de Mexico). STUDY UNITS: Ten articles randomly selected and considered as original research material published in 1987 from each journal were used. MEASUREMENTS: Eight terms were identified in each text of the selected articles: almost always, very probably, probable, probably, frequent, possible, improbable and almost never. MAIN RESULTS: One hundred and fifty three expressions were identified, for a global average of 3.8 expressions per article. No statistical significant differences were found between the journals in relation to the frequency with which the expressions were used (P = 0.76). When comparing the chapters of each article, significant statistical differences were found which disappeared when the comparison was rated. In 89% of the cases, the expressions did not have a referral which therefore did not allow for their quantification. Finally, those articles defined as "clinical" had a greater frequency of semiquantitative expressions than those considered as "biomedical" (4.2 vs 1.3 on the average, respectively). CONCLUSIONS: On the average, semiquantitative expressions are used four times per article, 75% of the times without a referral which would allow to quantify them, which could condition for a wide variety of interpretations on behalf of the readers. PMID- 2098038 TI - [Selective deficiency of IgA. Infrequent complications]. AB - The association of selective IgA deficiency and/or autoimmune disease is not uncommon. This article includes two rare associations, recurrent parotiditis and Turner syndrome, in two patients with selective IgA deficiency, IgA; IgA deficiency; recurrent parotiditis; Turner's syndrome. PMID- 2098039 TI - [An unusual case of systemic toxocariasis]. AB - Systemic toxocariasis generally causes fever, liver enlargement and lymph node swelling. This is an unusual case report which was initially confused with juvenile rheumatoid arthritis due to the presence of fever, arthralgias, arthritis of the smaller joints, important leukocytosis and hypergammaglobulinemia, besides testing positive for rheumatoid factor type IgM. After finding severe eosinophilia in both the patient's blood as well as in the bone marrow, systemic toxocariasis was diagnosed also finding very high levels of antibodies against Toxocara canis using the ELISA technique. Briefly discussed are the clinical and laboratory data, and the management of systemic toxocariasis and the possible origin of the rheumatoid factor in this disease. PMID- 2098040 TI - [Cloverleaf skull. Presentation of three cases]. AB - Three patients who presented cloverleaf skull are described. The first one associated with tanatophoric dwarfism, the second case was an isolate anomaly and the third one was associated with facial fissures. The three patients showed the outstanding diversity of the clinic manifestations encountered in this entity. The findings at central nervous system level, by computarized tomographic and ultrasonographic studies, are described. The relevance of genetic counselling is emphasized. PMID- 2098041 TI - [Congenital myasthenia gravis. Presentation of a case with dysphagia as the only clinical manifestation]. AB - Myasthenia gravis is an infrequent disease seen at the neonatal stage. Two main groups are identified: a) one with a genetic origin which can be secondary to pre or postsynaptic defects and b) of an acquired origin, as transitory neonatal myasthenia seen in 10-15% of those children with myasthenic mothers. Few cases with a genetic origin have been reported in the literature; the most common symptoms being bilateral eyelid ptosis, ophtalmoparesis, easy fatigability, respiratory and feeding difficulties. This is a report of a genetic neonatal case of myasthenia gravis with dysphagia as the only clinical manifestation seen since the first days of the child's life, confirming the diagnosis using a repetitive supramaximal stimulation test and obtaining excellent results with pyridostigmine. We conclude that, although this a rare form of the disease, genetic neonatal myasthenia gravis should be considered in the differential diagnosis of newborns with difficulties to swallow. The repetitive supramaximal stimulation test is the diagnostic procedure of first choice to be used in the neonatal period. PMID- 2098042 TI - [Biliary-enteric diversion with antireflux mechanism]. PMID- 2098043 TI - Fetal hydrocephalus. Clinical significance of associated anomalies and genetic counseling: a pathological approach. AB - We report on a consecutive series of 94 cases of fetal hydrocephalus. Pathological and neuropathological findings have been thoroughly analysed in order to define more precisely the clinical significance of associated anomalies and their implications in genetic counseling. In 90.5% of cases, hydrocephalus was associated with other central nervous system (84%) or extra neural (56%) anomalies. True aqueductal stenosis occurred only twice in our series. In only 9 fetuses, hydrocephalus was an isolated finding, secondary to haemorrhage or infection. Since fetal hydrocephalus is an etiologically heterogeneous disorder, its recurrence varies greatly. Without a final diagnosis, based on well documented pathological data and cytogenetic studies, accurate genetic counseling and prenatal diagnosis in subsequent pregnancies would be impossible. PMID- 2098044 TI - Cerebral midline developmental anomalies: spectrum and associated features. AB - Cerebral midline anomalies are defects of anatomical relationships between the two hemispheres. They include holoprosencephalies, septal and commissural agenesis. Agenesis of the olfactory tract (arhinencephalies) are often included in the spectrum of holoprosencephalies and the facial phenotype is thought to be affected and characteristic in the midline development abnormalities. This work concerns a review of the literature and personal experience in two units of Fetopathology in Paris. This study confirms the relationships between various cerebral malformations and their frequent association. However, arhinencephaly and moreover agenesis of corpus callosum should be considered as heterogeneous entities, often totally distinct and independent from the malformative process of the holoprosencephaly. In addition, if major facial anomalies such as cyclopia are almost pathognomonic for holoprosencephaly, minor malformations such as lateral facial clefts of cleft palates result from a great variety of malformative processes. PMID- 2098046 TI - Cytogenetic findings in a consecutive series of 478 patients with Turner syndrome. The Leuven experience 1965-1989. AB - In this report, we present the cytogenetic findings in 478 patients with Turner syndrome diagnosed in Leuven in the period 1965-1989. The karyotypic anomalies are classified into seven groups: 1) classic, 45,X karyotype (52.1%); 2) mosaic 45,X/46,XX (10.9%); 3) mosaic 45,X/47,XXX and other "super-female" cell lines (4.6%); 4) isochromosomes i(Xq) and i(Xp) (16.1%); 5) ring chromosomes r(X) (4.4%); 6) other structural aberrations of the X chromosome (7.7%); and finally 7) mosaic 45,X/46,XY patients (4%). The most pertinent chromosomal findings are briefly discussed and compared with previous reported surveys on subject. PMID- 2098045 TI - Male pseudohermaphroditism with persistent mullerian structures, mental retardation and Borjeson-Forssman-Lehmann-like features: a new syndrome? AB - We report two sibs with an undescribed MCA/MR syndrome. Both had a 46,XY chromosome constitution. The first patient is profoundly mentally retarded. Clinical features include short stature, coarse face, deep set eyes, microphthalmia, large ears, gynecoid obesity, imperforate anus, sacral spina bifida, pseudovaginal perineoscrotal hypospadias, persistence of Mullerian structures, and low gonadotrophin levels. His XY sib was raised as a girl. She was slightly mentally impaired. She had microphthalmia and large ears, and was short. A complete uterus with tubae and a single intraabdominal gonad with testicular organization were removed during infancy. Those anomalies do not fit any previously reported syndrome, although the general aspect of the propositus clearly resembles Borjeson-Forssman-Lehmann syndrome. Inheritance could be either autosomal recessive or X-linked. PMID- 2098047 TI - Turner syndrome: the Leuven experience (1965-1989) in 478 patients. I. Patient's age at the time of diagnosis in relation to chromosomal findings. AB - Within the past 25 years 478 patients with Turner syndrome have been diagnosed in the Leuven Centre for Human Genetics. After exclusion of 36 lost pregnancies, mostly first trimester spontaneous abortions, almost 20 per cent of the remaining 442 Turner syndrome patients have been early detected, i.e. before the age of two years. Moreover, a high prevalence of classic 45,X karyotype over other karyotypes was observed in this age group. The high mortality of prenatally diagnosed Turner syndrome fetuses is discussed here in view of the most common associated congenital malformations. PMID- 2098048 TI - Turner syndrome: II. Associated anomalies, mental performance and psychological problems in 218 patients diagnosed in Leuven in the period 1965-1989. AB - Selected medical and psychosocial problems in 218 Turner syndrome patients diagnosed at the Leuven Centre for Human Genetics are reported here. Special attention is paid to the associated congenital malformations, the mental performance and the occurrence of psychosocial and/or characterological difficulties. Mental underdevelopment was documented in 50 patients (22.9 per cent) and psychosocial and/or characterological problems in a total of 44 patients (20.2 per cent). This study confirms that in patients with Turner syndrome diagnosis special attention should be drawn to the mental development and psychosocial problems. PMID- 2098049 TI - Triphalangeal thumb and split foot in the same family. AB - The authors report a family with triphalangeal thumb with nail hypoplasia: one of them has also split feet. They believe that the existence of such families must make very circumspect with regard to genetic counseling for a minor problem such as triphalangeal thumb. PMID- 2098050 TI - Fertility in couples heterozygous for the tyrosinemia gene in Saguenay Lac-St Jean. AB - A case-control study of 84 couples from Saguenay-Lac-St-Jean, jointly heterozygous for the tyrosinemia gene, was done to determine whether the birth of an homozygous child affected their fertility rates. The mean number of children born to tyrosinemia and control couples between 1940 and 1986 was not different (p greater than 0.05). The knowledge that tyrosinemia was an autosomal recessive disorder, with risk of recurrence in these families, did not appear to modify reproductive behaviour. Fertility fell significantly in both the tyrosinemia and control families in the period of observation. This change reflects the decline in fertility of French Canadians in general during this period. PMID- 2098051 TI - Leg duplication and kidney agenesis: case report and pathogenic considerations. AB - A case is given of a male born with a total duplication of the left leg. In addition, ipsilateral kidney agenesis was found. Three possible mechanisms of leg duplication are given. The association with renal agenesis is discussed in terms of a polytopic developmental field defect. PMID- 2098052 TI - Medulloblastoma in the nevoid basal-cell carcinoma syndrome: case reports and review of the literature. AB - The nevoid basal-cell carcinoma syndrome (NBCCS) is a rare autosomal-dominant inherited disorder. Its clinical manifestations are multiple basal-cell nevi and cysts of the jaw along with skeletal anomalies and various combinations of numerous other defects. NBCCS is characterized by a marked propensity for developing cancers. One of the most frequently reported tumour is brain medulloblastoma. We are reporting two cases of NBCCS and medulloblastoma. A review of the case reports demonstrates certain prominent features of medulloblastoma associated with NBCCS. The patients generally are males, presenting at an unusually young age, under 5 or 2 years and show a longer survival rate. Its lay down to search for NBCCS in early medulloblastoma's, especially under 2 years. PMID- 2098053 TI - Wilhelm Weinberg, M.D. (1862-1937): the man behind the "Hardy-Weinberg equilibrium". PMID- 2098054 TI - Antitumor activity of methyl-4 H-1,2,4-benzothiadiazin-3-yl-carbamodithioate-S,S, dioxide. AB - The antitumor activity of the methyl-6-chloro-4H-1,2,4-benzothiadiazin-3-yl-S carbamothioate+ ++-S,S,-dioxide (1) and the methyl-4H-1,2,4-benzothiadiazin-3-yl carbamodithioate-S,S-di oxide (2), has been evaluated. Compound 2 passed activity criteria for leukemia P388 and was also moderately active against transplanted mouse tumor L1210 leukemia and M5076 sarcoma. PMID- 2098055 TI - Characterization of alpha and beta crystalline forms of nicardipine hydrochloride. AB - The aim of this work was the characterization of alpha and beta crystalline forms of nicardipine hydrochloride (coronary vasodilator drug) by means of DSC analysis, X-ray diffraction patterns, TLC analysis and IR spectroscopy. The results obtained show that it is possible to distinguish the two forms by means of these techniques. PMID- 2098056 TI - [Constituents of Umbilicus ruperstris (Salisb.) Dandy (Crassulaceae)]. AB - In the Umbilicus rupestris (Salisb.) Dandy, spontaneous in Genoa country, are present two heterosides with keratolytical action. The most aboundant is identical with venusol. PMID- 2098057 TI - Rapid reattachment of fractured crown segment: an update. AB - The technique of reattaching traumatically fractured crown segments using bonded tooth-colored materials has improved over the last decade. The latest advancement is the use of a new visible light-hardened glass ionomer material for rapid initial replacement of detached coronal structure. This paper demonstrates a step by-step procedure for coronal repair using light-hardened glass ionomer material and application of broad plane bonded composite resin for strength and natural appearance. PMID- 2098058 TI - Custom shade guide system for composite resins. AB - Shade guides that are included in most composite kits are not made of the actual resin material. Therefore the true shade, translucency, or opacity of the composite resin is not readily apparent with stock shade guides. Due to this fact, it has become evident that the best solution to the shade guide problem is to construct a custom shade guide from the actual resin. Until recently, fabrication of custom shade guides has been a time-consuming, inefficient task. Now, a simple and efficient method of forming accurate shade guides for composites is available. With its unique handle/template design, T-TABs enable a dentist to create a precise, labeled shade guide within minutes. There are many advantages to both dentist and patient when T-TABs are employed in the construction of custom shade guides. PMID- 2098059 TI - Class III acid-etch light polymerized composite resin restoration. AB - The use of an acid-etch enamel resin bonded Class III restoration allows for a more conservative cavity design. The acid-etch technique's benefits include retention without dentinal undercuts and creating reinforcement of undermined enamel. When a controlled method of acid-etched enamel resin-bonding with a syringe technique is used with a visible light curing composite resin, a durable, esthetic Class III restoration is achieved. PMID- 2098060 TI - Magnification in dentistry. AB - The use of today's highly sophisticated dental materials has required a corresponding increase in the technical skills of the operator. Surgical telescopes with high resolution and contrast are replacing plastic lenses of somewhat lesser quality. Moreover, depending on their frame mounting, these ground glass magnifiers are also offering the operator additional comfort and safety. The problem for the dentist, however, is to assess properly the products currently being presented by manufacturers. A detailed description of each device offered by four major suppliers is given relative to true field width and depth, working distance or range, "down time" during prescription changes, usefulness with correction, operator positioning, light admittance, degrees of magnification available, and expense. Photographs of the operator practicing without magnification and then using each of three devices is shown and analyzed. With some exceptions, those instruments providing the most flexibility as regards the above factors are most worthy of the dentist's consideration. PMID- 2098062 TI - Smile-imaging: the key to more predictable dental esthetics. AB - Smile-imaging is a new concept in dentistry that offers an impressive level of predictable and successful esthetic results. It is useful in the diagnosis, communication, and treatment phases of esthetic cases regardless of the treatment plan. Smile-imaging builds esthetics into the case instead of adding them on at the end. It is available to any dentist without having to spend time learning a computer program or investing in equipment. Full-face pictures of the patient are all that are required from the dentist. PMID- 2098061 TI - All porcelain anterior veneer bridges. AB - The introduction of new porcelain materials used in combination with vastly improved bonding materials and techniques have virtually revolutionized the use of conservative esthetic bonded prosthetic restorations fabricated without the need for metal substructures. Missing anterior teeth in selected cases may be replaced by all porcelain veneer bridges that are accomplished with more conservation of natural tooth structure of the abutment teeth as compared to traditional procedures. A total of 12 all porcelain veneer bridges were monitored for varying periods up to 24 months postoperatively, during which time no fractures occurred. The authors have attributed this high early success rate primarily to several factors, namely (1) case selection, (2) bulk of porcelain at the sides of the major connectors, and (3) adjustment of occlusion and articulation with the opposing teeth. PMID- 2098063 TI - Antimicrobial properties of VLC liners. AB - The antimicrobial activity of several visible light cured glass ionomer and liner materials against three bacteria commonly found in the oral cavity is discussed. Vitrabond light cure glass ionomer produced zones of inhibition against all the bacteria tested in this study. It appeared to resemble a true glass ionomer cement in regard to its antimicrobial properties whereas the other materials used in this study appeared to possess no antimicrobial activity. PMID- 2098064 TI - Evaluation of clinical performance of twelve posterior composite resins with a standardized placement technique. AB - The purpose of the study was to evaluate 12 posterior composite resins with a standard clinical placement technique that could be followed in a practice setting. Important points stressed are the use of rubber dam, care taken to detail on manufacturer's directions, incremental placement technique, and a standard finishing technique. Sixty-one Class II restorations were placed by a single operator. All of the restorations were evaluated at baseline, one and three years using the modified Ryge criteria. Indirect evaluation of wear was completed for each restoration using Leinfelder's technique. Two percent of the restorations at 1 year and 17 percent at 3 years were not clinically acceptable. PMID- 2098065 TI - Emergency dentures and esthetics. AB - Accidents occur in life and when they affect the dentition, whether natural, artificial, or a combination, they can result in a feeling of dread and despair in the patient. The thought of appearing not only in public with business and social acquaintances, but also in private with family members can be reprehensible. This article discusses the use of visible light-cured denture base materials that can be used to alleviate the fear these patients display in being exposed to socio-esthetic intercourse when becoming suddenly partially edentate. The method of use and three patients' photographic essay presentations are discussed. PMID- 2098066 TI - Insights and innovations. PMID- 2098067 TI - Immunologic privilege evoked by histoincompatible intracameral retinal transplants. AB - In order to examine the fate of intraocular retinal transplants, we placed histoincompatible neural retinas from neonatal BALB/c mice into the anterior chamber (AC) or subconjunctival space of eyes of adult C57BL/6 mice. Clinical and histologic examinations revealed that grafts of developing neural retinal tissue placed within the AC acquired a blood supply, and differentiated into histologically recognizable retinal structures; there was no evidence of inflammation or rejection. By contrast, developing neural retinal allografts placed in the subconjunctival space failed to thrive, and were promptly rejected within 8 days. To examine the nature of the systemic immune response of mice bearing intracameral retinal allografts, C57BL/6 mice, bearing neural retinal allografts from BALB/c donors in their AC for 12 days, were tested for delayed hypersensitivity. When ear challenged with (C57BL/6 x BALB/c)F1 spleen cells, these mice failed to mount significant ear swelling responses, whereas a positive control group of C57BL/6 mice that received neonatal BALB/c retinas implanted in the subconjunctival space displayed vigorous BALB/c-specific delayed hypersensitivity. It is pertinent that, shortly after ear challenge with (C57BL/6 x BALB/c)F1 cells, the previously healthy AC retinal allografts underwent regression and degeneration. Finally, we showed that the spleens of C57BL/6 mice bearing healthy intraocular developing retinal allografts contained suppressor lymphocytes that were revealed in adoptive transfer assays. We conclude that immune privilege is extended to histoincompatible developing retinal transplants placed in the AC of the eye, and that these allografts induce a deviant systemic immune response characterized by impaired expression of delayed hypersensitivity and generation of splenic suppressor cells. We infer that the success of these transplants, compared to similar grafts which are rejected in the subconjunctival space, is predicated upon, and mediated by, the induction of active specific suppression of cell-mediated immunity. PMID- 2098069 TI - Tumor necrosis factor-alpha and ultraviolet B light have similar effects on contact hypersensitivity in mice. AB - Acute, low dose ultraviolet B (UVB) radiation impairs the induction of dinitrofluorobenzene (DNFB)-specific contact hypersensitivity (CH) in some, but not all, inbred strains of mice. Although C3H/HeN mice are UVB-susceptible by these criteria, the closely related strain, C3H/HeJ proved to be UVB-resistant. Since the only known important genetic difference between these strains is a polymorphism at the Lps locus which governs sensitivity to bacterial lipopolysaccharide (LPS), we examined the possibility that UVB radiation achieves its immune effects via an action directly or indirectly related to LPS. We found that intradermal injections of LPS failed to impair the induction of CH when DNFB was painted at the skin injection site. However, tumor necrosis factor-alpha (TNF alpha), a cytokine released from LPS-sensitive macrophages by exposure to LPS, was able to suppress CH induction when it was injected intradermally (50 ng) prior to epicutaneous application of hapten. In addition, systemic administration of larger doses of TNF alpha (200 ng) inhibited CH, whether the cytokine was injected intraperitoneally at the time of cutaneous sensitization with DNFB, or prior to ear challenge with the hapten. Importantly, when TNF alpha was injected into pinnae of DNFB-immune mice prior to elicitation of CH, local inflammatory responses were greatly exaggerated. Thus, TNF alpha shares with acute, low dose UVB radiation the following effects on CH: impairment of induction, and amplification of expression. These effects are only achieved following local treatment with these agents. We propose that TNF alpha is an important cytokine mediator of the effects of UVB on hapten-specific CH. PMID- 2098070 TI - Pediatric dentistry as a metaphor for life: the big Q. PMID- 2098068 TI - Induction of an enteric Ig-response against ovalbumin and stimulation of the response by cholera toxin and its B-subunit in mice. AB - We induced ovalbumin (OA)-specific antibody responses in the murine small intestine and quantitated the responses by counting ovalbumin-specific antibody containing cells (OACC) in the intestinal lamina propria, and by measuring anti OA Ig titers in intestinal secretions. OA is a "weak" mucosal antigen and we could only induce intestinal anti-OA responses by intraperitoneal, primary injection of OA in water-in-oil emulsion and a mucosal booster with OA. Double staining of OACC for OA- and isotype-specificity demonstrated that 95% of all mucosal (intestinal) OACC produced IgA, whereas 95% of all systemic (splenic) OACC produced IgG. The intestinal anti-OA response could be stimulated by addition of cholera toxin (CT) or cholera toxin B-subunit (CTB) during the mucosal booster immunization. The stimulatory effect of CT did not depend on covalent coupling of CT and OA, while the stimulatory effect of CTB required covalent coupling of CTB with OA. Mucosal (intraduodenal) application of OA as such does not prime for a mucosal and systemic OACC response but induces tolerance. We demonstrated that coupling of OA with CT or CTB could overcome the inability of mucosal application of OA to prime for a mucosal OACC response. Although CT proved to be much more effective than CTB in stimulation of mucosal immune responses and possibly in prevention of tolerance induction, our results indicate that CTB is a useful (and safer) alternative. PMID- 2098072 TI - Ideas that build your practice: 1. PMID- 2098071 TI - Comparative review of the state of Michigan dental Medicaid program: a guide to substandard care. PMID- 2098073 TI - Pedodontic electrosurgery. PMID- 2098074 TI - Progressive external resorption of a maxillary central incisor following avulsion: a new prosthetic approach. PMID- 2098075 TI - Prevention of overbite and overjet development in the 3 to 8 year old by controlled nighttime guidance of incisal eruption: a study of 43 individuals. AB - The purpose of this study conducted at Tufts University School of Dental Medicine is to investigate the possibility of limiting the development of an excessive vertical overbite and horizontal overjet during sleeping hours in young children prior to and during the eruption of the permanent incisors. A sample of 43 individuals, whose mean age was 6.17 years, wore a Preventive Eruption Guidance Appliance passively only while sleeping at night for 13 months (mean) to control the development of the overbite as the permanent incisors erupted and to correct the excessive overjet. The mean initial overbite of the sample was 3.4 mm and was reduced to 1.4 mm. The mean initial overjet was 3.0 mm and was reduced to 1.4 mm. Fourteen percent (6 cases) of the sample had an open bite of 1.84 mm (mean), which was reduced to a mean open-bite of 0.81 mm. As a result of the statistical comparison between the treatment sample to the control sample of 50 non-treated individuals, it was shown that the reduction of the overbite and overjet was accomplished solely by altering the problematic dentition without affecting the normal growth pattern or facial morphology as measured from nine lineal dimensions. It was also shown that the change in overbite and overjet was a significant improvement over what would have occurred if no intervention had been instituted, and that the overbite was corrected by restricting continued excessive eruption of the maxillary incisors with only nighttime passive use of the appliance. PMID- 2098076 TI - Mineralizing agents in caries prevention: a review of the effects of Remodent. AB - Caries reduction from tooth brushing with Remodent occurs according to age, from 37.8% to 83.7% during a two to three year follow-up. The highest reduction was gained when the program was started at the age of 2. When Remodent-solution and varnish were tested in one to three year follow-up, reductions in caries occurred from 20% to 91%. These studies also showed that the effect was best when the preventive treatment was started early. PMID- 2098077 TI - Enamel hypoplasia in prematurely-born children: a scanning electron microscopic study. AB - Although the enamel defects of low birthweight prematurely-born children have been well investigated clinically the ultrastructure has not been studied in detail. Using scanning electron microscopy this investigation examined the enamel surface of 4 representative teeth from a group of exofoliated teeth from prematurely-born, very-low birthweight children compared to an equal number of control teeth from normal birthweight children. The results showed that all 4 teeth from the prematurely-born group had enamel defects at the ultrastructural level even though the defects were evident only macroscopically in 2 teeth. By contrast all the control teeth from normal children did not show abnormalities of surface structure. Thus this investigation further confirms that birth prematurity and low birthweight adversely affect the activities of ameloblasts. Previous clinical investigations have reported that prematurely-born children show high prevalences of enamel hypoplasia of around 20-100%. The etiological factors involved in the pathogenesis of enamel defects are unclear, but are likely to be related to many systemic illnesses occurring during the neonatal period. These include respiratory distress syndrome, hyperbilirubinemia, maternal diabetes as well as neonatal rickets. Furthermore, Seow et al. (1989) showed recently that deficiency of calcium and phosphate mineral in the neonatal period is related directly to enamel hypoplasia in very-low birthweight, prematurely born children. In addition to systemic factors, local factors such as laryngoscopy and endotracheal intubation have also been implicated in the etiology of enamel hypoplasia in these children. While the enamel defects have been well studied at the clinical level, there is a paucity of information on the ultrastructural nature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098078 TI - Appliance effects on the masseter and temporal muscle electromyography of patients with facial asymmetry. AB - The usual symmetrical EMG recordings were disturbed in all 5 cases of asymmetrical dentofacial deformity. A marked electrical activity of the masseter and temporal muscles opposite to the site of the lesion was observed. PMID- 2098079 TI - Utilization, knowledge and attitudes concerning sealants among Malaysian dentists: a national survey. AB - The aim of this postal survey was to assess the utilization, knowledge and attitude concerning sealants among Malaysian dentists. A pretested questionnaire was sent to all dentists (1217) who were on the Dentist Register of Malaysia of 1987. A response rate of 61.1% was obtained. The results indicate that 52.6% of the respondents have used sealants, but of these only 13.6% have used them frequently. The two "knowledge" related questions receiving the most support concerned the suitability of the first permanent molars for sealants and the loss of sealants attributable to problems at the time of application. The two "attitudinal" questions receiving the most support concerned the value of sealants in preventing dental caries and the need for the profession to expand more efforts toward increasing public demand for sealants. Only about 50% of the respondents believed that sealants are cost-effective. PMID- 2098081 TI - Cross-sectional study to evaluate variations in attached gingiva and gingival sulcus in the three periods of dentition. AB - The dimensional differences of the attached gingiva and gingival sulcus in the primary, mixed and permanent dentition were studied clinically in normal gingivae of 382 children, aged 4-15 years. The depth of the gingival sulcus and the width of keratinized gingiva were also measured. Shallow gingival sulcus was observed in the primary dentition as compared to that in permanent dentition. However, in the mixed dentition deeper sulcus was observed around the newly erupted teeth. This was attributed to deeper penetration of the instrument, at the time of eruption. The widest zone of attached gingiva was observed in maxillary and mandibular incisors, decreasing gradually over the cuspids and first premolars (first primary molars), and again attached gingiva increased in second premolars (second primary molars) and first and second permanent molars. The width of attached gingiva in case of newly erupted permanent teeth (mixed dentition) was narrower in the corresponding primary teeth. This was due to an increase in the gingival sulcus depth. The attached gingiva increased in width with age. This was related to a concomitant reduction in sulcus depth. PMID- 2098080 TI - Direct composite onlay technique for primary molars using a light/heat curing system. PMID- 2098082 TI - Relationships between socioeconomic status, gingival health and oral hygiene in schoolchildren. PMID- 2098083 TI - Role of developmental stage of occlusion for articulatory disorders in speech among first-graders. AB - The purpose of this study was to examine the role of the eruption stage and that of occlusal anomalies among etiological factors for articulatory speech disorders in a series of first-graders. The results suggest that even though speech and sound production have been reported to be mature by the age of five, some spontaneous correction of speech sound articulation occurs with maturing of the articulators with age and with eruption of some permanent teeth during the first phase of the mixed dentition. PMID- 2098084 TI - Agenesis of the second premolar in males and females: distribution, number and sites affected. AB - One of the most common anomalies of the dentition is congenitally absent second premolars and this form of hypodontia may occur as an isolated trait or in association with a syndrome. Using radiographs and clinical examinations, hypodontia of second premolars was assessed in 176 subjects (80 male and 96 female). Distribution of the hypodontia was assessed according to site and number missing in males and females. No significant differences were observed in males and females with respect to the number of premolars absent, sites affected or symmetry of the agenesis. Agenesis of a single second premolar was the most common form of this hypodontia with absence of three second premolars occurring least frequently. PMID- 2098085 TI - Relation of ectodermal dysplasia and hypodontia. AB - Ectodermal dysplasia and hypodontia were diagnosed in three families who referred to Gazi University Pedodontic Department in 1989. From the view point of dentistry, it is intended to point out the genetic transitive character of ectodermal dysplasia and its possible relation with hypodontia. Also; some approaches to satisfy the patients in social and psychological aspects besides replacing the functional and cosmetic demands were carried out. PMID- 2098086 TI - Objectifying treatment of malocclusion. AB - Presently there are several controversial areas in the clinical practice of dentistry. One area which presents an ethical dilemma to the clinician is the delivery of quality and sufficiency of treatment of malocclusion. The mode of treatment of malocclusion by orthodontists, pediatric dentists, generalists represents a classic turf battle with its potential ethical problems. The author calls for objectified standards of care which help to preserve ethical values related to our patients. Clinical research is presented to help focus on this ethical dilemma. PMID- 2098087 TI - Caries incidence in children with acyanotic congenital heart diseases before and after the heart operation. AB - An acyanotic cardiac disease (ASD) was diagnosed in a 9-year-old girl with a very high caries incidence and premature tooth eruption. After the heart operation her caries incidence declined considerably. An epidemiological survey was then conducted to find out if these observations could be generalized. dmf-t, dmfs, DMF-T and DMFS values for each year were counted retrospectively for a group of acyanotic heart diseased children operated on at the age of 5-7 years (mean 6) and another group operated on at the age of 10-13 years (mean 12), from the documents relating to annual examinations conducted by the public health dental services. The results were compared to those of healthy children matched for age and sex living in the same area. Heart disease resulted in DMF-T values above the control level in the group operated on at age 6 years, whereas the values were lower than the controls in the group operated on at age 12 years, the difference being significant after the operation in the latter case. It is concluded that acyanotic congenital heart disease may lead to a higher caries prevalence and sometimes rampant caries. When the caries prevalence of the population is high, however, (DMF-T higher than 4.5 at 12 years), the effect of heart disease remains hidden. PMID- 2098088 TI - Gender and homicide: a comparison of men and women who kill. AB - This study compares the patterns of homicides committed by women and men. Classic comparison studies of homicides by men and women suggest that each group kills in ways that are reflective of socially approved gender role behavior. More recently, however, research on women who kill suggests that they frequently do so in response to threats of violence by men. In contrast to the gender role and self-protection models of women's homicides, the liberation hypothesis suggests that patterns of women's violence will increasingly resemble patterns of violence by men. Based on our analysis of court records of 158 cases of homicides by men and women over a six-year period, we find little support for the liberation hypothesis and considerable support for the gender role and self-protection models. Compared to men, women more frequently kill intimates and kill in situations in which their victim initiated the physical aggression. PMID- 2098089 TI - Interventions with battered women in health care settings. AB - Over the past decade advocates for battered women in the health care system, citing the large number of battered women who come to health care settings, have proposed interventions and trainings for health care personnel on behalf of battered women. However, little is currently known about the effectiveness of intervention efforts. This paper presents observation data on characteristics of battered women in four hospital Emergency Departments (EDs) and on staff responses to battered women in these EDs. The data show definite patterns in the women's characteristics and in staff responses to battered women. These data raise issues which should be considered in the researching and designing of interventions for battered women in the health care system. PMID- 2098091 TI - Acceptance of guided imagery of marital rape as a function of macho personality. PMID- 2098090 TI - Patriarchal ideology and wife beating: a test of a feminist hypothesis. AB - Feminist theory suggests that husbands who adhere to an ideology of familial patriarchy are more likely to beat their wives than husbands who do not adhere to such an ideology. This research provides quantitative data from a representative sample survey of women in the general population that support the feminist thesis. The results also indicate that husbands with relatively low incomes, low educational attainment, and low-status jobs were significantly more likely than higher status husbands to espouse such an ideology. PMID- 2098092 TI - Child victims of homicide: a portrait of their killers and the circumstances of their deaths. AB - The population of 93 arrestees for homicides committed against children between 1982 and 1986 in Detroit, Michigan, is analyzed in the context of their killings. Analyses include demographic and social characteristics of offenders and victims, demographic and social relationships between offenders and victims, circumstances of offense, and arrest disposition. Where feasible, comparisons are made with general populations and samples of homicide offenders. PMID- 2098093 TI - Three cases of congenital hepatic fibrosis with Caroli's disease in three siblings. AB - Congenital hepatic fibrosis is a relatively rare disease of children and young adults characterized by hard hepatomegaly, portal hypertension with relative preservation of liver function and underlying architecture, and frequent renal involvement. We experienced 3 cases of congenital hepatic fibrosis with Caroli's disease in 3 siblings, whose clinical manifestations were diverse, such as repeated cholangitis, variceal hemorrhage, or intrahepatic stones. All of them had multiple renal cysts, so we supposed that the clinical entities of these patients were in the spectrum of fibropolycystic disease of the liver and kidney. PMID- 2098094 TI - A case of adrenal lymphangiectatic cyst associated with severe hypertension. AB - Adrenal lymphangiectatic cyst is a very rare pathological and clinical disease entity, and its clinical silence and lack of characteristic symptoms and signs makes it difficult to diagnose preoperatively. We experienced a case of adrenal lymphangiectatic cyst, accompanied by severe refractory hypertension, which was corrected by surgical removal of the cyst. We report it with a review of the literature. PMID- 2098095 TI - Electrocardiographic changes simulating acute myocardial infarction or ischemia associated with combination chemotherapy with etoposide, cisplatin, and 5 fluorouracil. AB - Three cases of cardiotoxicity manifested by chest pain, tachycardia, respiratory distress, and electrocardiographic changes simulating acute myocardial infarction or ischemia were observed during the course of combination chemotherapy with etoposide, cisplatin, and continuous infusion of 5-fluorouracil in patients with advanced non-small cell lung cancer. There was no cardiac enzyme elevation. A similar but rare clinical syndrome has been described in association with 5 fluorouracil infusion as a single agent or in combination with other chemotherapeutic agents. We describe the cases and review their possible pathogeneses and clinical implications. PMID- 2098096 TI - A case of laboratory-acquired murine typhus. AB - We encountered a 32-year-old Korean woman who developed murine typhus in a laboratory. She worked as a technician in a laboratory for rickettsial disease. Immunofluorescence test with rickettsial antigen (R. typhi) was positive at 1: 320 on admission and 1: 1280 after 4 weeks. A dose of 200 mg of doxycycline for 7 days proved to be effective for her condition. PMID- 2098097 TI - A simple quantitative assay of vascular plasminogen activator--not only stimulated fibrinolytic activity but also basal fibrinolytic activity are correlated with venous fibrinolytic activity. AB - A simple method for the quantitative assay of vascular plasminogen activator is described. From 24 chronic renal failure patients who were undergoing surgery for A/V fistular or shunt construction, small pieces of artery (mean 7.8 mg, range 3.0-18.5 mg) and vein (mean 4.5 mg, range 3.0-8.8 mg) were used. The fibrinolytic activity was assayed on a well-controlled fibrin plate by only distilled water immersion and incubation at 37 degrees C. Basal fibrinolytic activity was correlated with venous fibrinolytic activity (r = 0.773, p less than 0.0001) and with arterial fibrinolytic activity (r = 0.55, 0.005 less than p less than 0.01). The increment of fibrinolytic activity by venous occlusion was correlated to venous fibrinolytic activity (r = 0.849, p less than 0.0001) but not to arterial fibrinolytic activity (r = 0.34, 0.1 less than p less than 0.25). PMID- 2098098 TI - Defective response of natural killer activity to thyroxine in Graves' disease. AB - The effect of thyroxine (T4) on natural killer (NK) activity of peripheral blood lymphocytes (PBL) was investigated, using a 4-hr 51Cr release assay, in 18 patients with previously untreated Graves' disease and in 18 controls. NK activity in patients with Graves disease was not significantly different from that in the controls. Normal T4 (NT) and high T4 (HT) medium, free T4 concentrations in which were 1.01 and 16.3 ng/dl, respectively, were used to evaluate the effect of T4 on NK activity. In the controls, NK activity increased in the NT or HT medium compared with that in the control medium at effector to target cell (E:T) ratios of 25 : 1 and 50 : 1. NK activity in the Graves' disease patients, however, did not increase when either the NT or HT medium was used at E : T ratios of 25 : 1 and 50 : 1. These results suggest that patients with Graves' disease have a similar NK activity to the controls but have a defect in the peripheral blood lymphocytes to increase NK activity in response to T4. PMID- 2098099 TI - Determinants of magnitude of pseudohyperkalemia in thrombocytosis. AB - The release of potassium from platelets is a well-known cause of pseudohyperkalemia in thrombocytosis. In predicting the magnitude of pseudohyperkalemia associated with thrombocytosis, previous investigations considered only the amount of potassium released from platelets during blood clotting, although the increment in serum potassium during blood clotting depends on the quantity of potassium released from platelets as well as the volume of distribution of the released potassium, which is inversely proportionate to the hematocrit. The present study proposes a new mathematical formula to predict the magnitude of increase in serum potassium during blood clotting, and accuracy of this formula has been tested in a patient with thrombocytosis. PMID- 2098100 TI - Denaturing gradient gel electrophoretic analysis of the human cHa-ras1 proto oncogene. AB - Activation of ras proto-oncogenes frequently involves point mutations at different sites in the gene. Here we describe the application of denaturing gradient gel electrophoresis to identify and characterize such mutations in the cHa-ras1 proto-oncogene. We calculated a melting map of the cHa-ras1 gene and designed optimal conditions to separate mutant from wild type sequences in the first exon. As an example we examined the T24 guanosine to thymidine point mutation in the first exon which has been found in T24 bladder carcinoma cells. Denaturing gradient gel analysis of both homoduplex as well as heteroduplex molecules resulted in separation of the wild type sequence from the mutant sequence. On the basis of the melting map we present a general scheme for screening the cHa-ras1 proto-oncogene sequence for the occurrence of point mutations. PMID- 2098101 TI - Serum autoantibodies in type 1 (insulin-dependent) diabetes mellitus: identification of reactivity against a 29 kd pancreas-specific protein. AB - Serum samples from patients with type 1 (insulin-dependent) diabetes mellitus and controls were incubated with two-dimensional Western immunoblots of pancreas and other tissues. Two out of 26 (8%) of the diabetics and 0 out of 45 of the controls demonstrated reactivity against four pancreas-specific proteins with identical molecular weights of 29,000 daltons and different isoelectric points ranging from pH 7.0-8.0. It is concluded that 29 Kd autoantibody reactivity is not a major marker for type 1 diabetes, but may help identify a subgroup of type 1 diabetics. PMID- 2098102 TI - Two-dimensional electrophoresis of proteins: a simple procedure for casting of narrow-bore, first dimension (isoelectric focusing) polyacrylamide tube gels. AB - A convenient and rapid method for casting of narrow-bore (1.5-2.5 mm, i.d.) first dimension isoelectric focusing gel tubes is described. The procedure utilizes a peristaltic pump and a 2-inch, 23 gauge blunt needle for dispensing the gel into fixed tubes on a 1.1 degree incline. The method is simple to perform, precludes the formation of air bubbles and little or no manual dexterity is required. PMID- 2098104 TI - The optimal conditions for protein analysis of Treponema pallidum subsp. pallidum by one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - Sample solubilization techniques can influence the protein patterns obtained by SDS-PAGE. In this study we determined the effects of the amount of SDS present in the sample solubilization buffer on one and two dimensional (1D and 2D) electrophoretic protein profiles of radiolabeled T. pallidum as well as the antigenicity of treponemal proteins as judged by Western blots of 1D and 2D gels probed with pooled secondary human syphilitic sera. Although the total number of protein bands in 1D profiles obtained at SDS concentrations between 0-5% was not significantly different, there was an obvious shift in the location of the bands. However, a significant amount of variation (including isoelectric point and molecular weight shifts) was observed among the total number of protein species in 2D profiles. The greatest number of protein species (158 total) was obtained with 3% SDS in the solubilization buffer, followed by the 1% SDS giving raise to 143 protein species. The highest number of proteins (59 total) detected on Western blots of 2D profiles was obtained when no SDS was used. The number of antigenic proteins in 1D profiles followed a bell shaped curve with 2% SDS giving the highest number (32 total) of the antigenic proteins. With different concentrations of SDS, the number of antigenic proteins in 2D profiles decreased as the concentration of SDS increased. Thus, we conclude that, 2% SDS in the sample solubilization buffer is best for 1D profiles. However, SDS is not recommended to separate all of the antigenic proteins in 2D gels. PMID- 2098103 TI - Separation and characterization of fibronectin domains by two-dimensional electrophoresis. AB - Two-dimensional gel electrophoresis (2DGE) and image processing were used to quantify protein and carbohydrate heterogeneity in human plasma fibronectin (FN) and its enzymatically produced domains. After a 30 minute thermolysin digest of FN, the domains were identified in 2DGE by their known isoelectric points and molecular weights, which were compared to domain standards purified by hydroxyapatite, gel exclusion and heparin-Sepharose chromatography. Three individual species were observed in the cell binding domain which may correspond to the heterogeneity known to result from alternative splicings of the fibronectin gene. In addition, the carbohydrate heterogeneity in the gelatin binding domain was analyzed by 2DGE and isoelectric focusing (IEF) before and after treatment with N-glycanase and neuraminidase to remove selected carbohydrate moieties. Five individual species which differ in carbohydrate structure were observed. The results also indicate a carbohydrate dependent stabilization of the gelatin binding domain with respect to proteolytic digestion. PMID- 2098105 TI - Analysis by isoelectric focusing of xanthine oxidase and NADH dependent enzymes in rat kidney. AB - Ultrathin isoelectric focusing was employed for analyzing xanthine oxidase and enzymes with NADH-dependent dehydrogenase activity in homogenates of rat kidney. After isoelectric focusing the enzymes were stained with specific assays where NBT is reduced upon incubation of the gel with xanthine (oxidase stain) and NADH (dehydrogenase stain) as substrates. A good separation of renal enzymes with dehydrogenase activities was obtained by using gels containing 2 M urea and by applying the sample at the anode. In these conditions 4 main isoforms with pI 6.4, 6.35, 6.5 and 6.6 were observed with the dehydrogenase stain but we were unable to demonstrate renal xanthine oxidase (XO) which seemed to be due to precipitation at the application point. PMID- 2098106 TI - Using starburst dendrimers as linker molecules to radiolabel antibodies. AB - Starburst dendrimers, spherical polymers constructed from methyl acrylate and ethylenediamine, were successfully used to covalently couple synthetic porphyrins to antibody molecules. The dendrimers, as linker molecules, have great potential for increasing the specific activity of radiolabeled antibodies for tumor therapy and diagnosis. PMID- 2098107 TI - Synthesis and characterization of digoxin-phospholipid conjugates. AB - The preparation of immunoreactive derivatives of digoxin for analytical applications is most often carried out by periodate cleavage of the terminal sugar ring (digitoxose) followed by reaction with an enzyme, protein, carrier, or related biological molecules. Here we report an improved and more efficient synthesis which was developed to provide digoxin-phospholipid conjugates useful for liposome immunoassay. The approach used involved the linking of the cleaved digitoxose through a carboxymethyl oxime functionality, which provides much improved yields of readily purified products. The synthetic modification should be applicable to the preparation of analogous phospholipid conjugates involving linkage through a sugar ring (digitoxin, ouabain, and related cardiac glycosides) or to those involving steroids (i.e., 3-digoxigenone) which can be modified to form oxime derivatives remote from key functionalities important for immunorecognition by specific antibody. The characterization of the digoxin phospholipid conjugates with high-resolution NMR and fast atom bombardment mass spectrophotometry will also be discussed. PMID- 2098108 TI - Misonidazole conjugates of the colorectal tumor associated monoclonal antibody 17 1A. AB - The radiation sensitizer misonidazole has been linked to the monoclonal antibody 17-1A which recognizes a nonshed antigen of a human gastrointestinal tumor. Linkage was accomplished through a hemisuccinate of misonidazole attached by a mixed anhydride coupling and gave a conjugate whose plasma half-life (for drug cleavage) was ca. 70 h. The degree of substitution on the antibody could be precisely regulated by varying the reactant ratios. The binding avidities of the resulting conjugates to the SW1116 colorectal tumor cells decrease logarithmically with increasing drug load. Four to six misonidazoles per antibody represented the optimum drug loading on this system. Enzymatic cleavage of the conjugate-drug union took place at both the ester and the amide linkages with the former scission predominating. PMID- 2098109 TI - Synthesis and interactive properties of an oligonucleotide with anthraquinone at the sugar fragment. AB - The synthesis of a self-complementary oligonucleotide possessing an anthraquinonylmethyl substituent at the designated sugar fragment, 5' CCU(2'AQ)AGCTAGG (1), is described. The anthraquinonylmethyl group was introduced to 2'-hydroxyl moiety of uridine, which was then converted to the protected phosphorobisdiethylamidite derivative. This reagent was used for the solid-phase synthesis of the modified oligonucleotide 1. The UV and CD melting behaviors indicate that the modified oligonucleotide 1 can form a duplex in aqueous buffer solution similar to the unmodified strand 5'-CCTAGCTAGG (7). The observed melting temperatures for the duplexes 1 and 7 were 57.4 and 40.0 degrees C, respectively. The temperature-dependent change in the intensity of the induced CD at around 335 nm reflected directly to the melting behaviors of duplex 1, indicating that the anthraquinone groups intercalate into the base pairs in the duplex. The intercalation-induced stability of the duplex translates into a free energy cost of 5.2 kcal/mol. The present work provides a novel method for enhancing the affinity of oligonucleotides for their complementary sequences. PMID- 2098110 TI - Immunotoxin construction with a ribosome-inactivating protein from barley. AB - The aim of this study was to determine the suitability of a ribosome-inactivating protein (RIP) from barley endosperm for use as an immunotoxin. This barley RIP is identical with the 30-kDa protein first reported by Coleman and Roberts [(1982) Biochim. Biophys. Acta 696, 239] and sequenced by Asano and co-workers [(1986) Carlsberg Res. Commun. 51, 75]. Use of the terms barley toxin I, II, and III is proposed to describe the three isoforms resolved by cation-exchange chromatography. An improved procedure for isolating the protein involving the steps of aqueous extraction, ammonium sulfate precipitation, and cation-exchange HPLC is described. Barley toxin II retained activity after exposure to ca. 40% acetonitrile and 0.1% trifluoroacetic acid or lyophilization. In a comparative study using the rabbit reticulocyte lysate assay, the protein was about 68% and 30% as potent as gelonin and ricin A-chain (RTA), respectively. Introduction of SH groups with 2-iminothiolane resulted in a substantial loss of activity as the number of thiol groups approached four. Therefore, it was necessary to limit thiolation to an average of one to two SH groups per toxin molecule. Anti transferrin receptor-based immunotoxins constructed with RTA, gelonin, and barley toxin II exhibited comparable cytotoxicity against a human colon tumor cell line. We conclude that the availability of raw material, ease of purification, and stability of barley toxin II to lyophilization and denaturing conditions render it a suitable protein for the construction of immunotoxins. PMID- 2098111 TI - A photoactive phosphonamide derivative of GTP for the identification of the GTP binding domain in beta-tubulin. AB - A GTP photoaffinity probe (125I-APTG) was developed that incorporated an [125I]-N (4-azidophenyl)-2-amino-3-(4-hydroxy-3-iodophenyl)propionamide group at the gamma position of GTP through a phosphonamide linkage. A combination of saturation and GTP protection studies (90% protection at 25 microM GTP with an apparent Kd of 5 microM) validated the use of this new probe as a satisfactory GTP mimic. This probe offered the advantage of possessing an 125I radiolabel external to the GTP moiety, in contrast to the previously reported [gamma 32P]-8-N3GTP that possessed an internal 32P radiolabel. This novel feature accommodated the purification of photolabeled peptides using a combination of ion-exclusion, gel filtration, and HPLC techniques. [125I]APTG was used to identify a peptide (beta:65-79) in the exchangeable GTP-binding domain of the beta-subunit of tubulin. PMID- 2098112 TI - Synthesis and evaluation of two new bifunctional carboxymethylated tetraazamacrocyclic chelating agents for protein labeling with indium-111. AB - The synthesis of two new N- and C-functionalized tetraazamacrocyclic ligands intended to be covalently linked to biomolecules like monoclonal antibodies and to bind the gamma-emitting isotope indium-111 in a thermodynamically and/or kinetically inert way is described. 12-(p-Nitrobenzyl)-1,4,7,10 tetraazacyclotridecane-1,4,7,10-tetraa cetic acid (L1) was synthesized by means of bimolecular cyclization with the appropriate malonic acid diethyl ester and triethylenetetraamine, followed by reduction with diborane and alkylation of the cyclic tetraamine with bromoacetic acid. The corresponding triscarboxymethylated ligand L2 was made by statistical alkylation of the tetraamine. Both ligands fulfill the criteria for antibody labeling using the bifunctional chelate approach, namely fast chelate formation, high radiochemical yield, and high stability under physiological conditions. Surprisingly the heptadentate ligand L2 confers higher stability to In3+ and exhibits faster complex formation than octadentate L1. 13C NMR spectra in solution indicate that the difference in stability is not due to incomplete coordination of all four carboxylate groups in In-L1. PMID- 2098113 TI - Cellular mechanisms of antigen processing and the function of class I and II major histocompatibility complex molecules. PMID- 2098116 TI - [Leptospirosis]. PMID- 2098114 TI - Transforming growth factor alpha and a PC12-derived growth factor induce neurites in PC12 cells and enhance the survival of embryonic brain neurons. AB - We have identified and characterized a 5000-Da protein that induces neurite outgrowth from PC12 pheochromocytoma cells, enhances the survival of embryonic rat brain neurons in primary culture, and induces the multiplication of embryonic rat brain astrocytes in primary culture. The factor is produced by a flat cell PC12 variant that expresses the activated ras oncogene after transfection of the gene. The factor resembles transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) in that it induces anchorage-independent colony formation of normal rat kidney cells in soft agar and competes with EGF for binding to the EGF receptor. Rat TGF alpha and human TGF alpha also induce neurite outgrowth from PC12 and enhance the survival of embryonic brain neurons. The PC12 variant-derived factor can be distinguished from TGF alpha and EGF immunologically and by migration rates on reversed-phase high-performance liquid chromatography. PMID- 2098117 TI - [Severe leptospirosis. Description of a series of 10 cases]. AB - Clinical aspects of 10 consecutive patients hospitalized for acute human leptospirosis, confirmed by serology using the microscopic agglutination test (MAT), between 1975 and 1988 in a 1000 beds Teaching Hospital are retrospectively analyzed. All of them were male, mean age of 55, presenting a suggestive epidemiological data to be at risk for Leptospira infection. Leptospira icterohaemorrhagiae was responsible for 8 cases and Leptospira canicola for 2. 7 patients were treated, after 3-4 days of admittance, with penicillin. 5 patients died. Cause of death was gastrointestinal haemorrhage in 3 and cardiogenic shock in 2. We discuss the clinical, biochemical, pathological and therapeutic aspects of the acute human leptospirosis. PMID- 2098115 TI - H-ras(val12) induces cytoplasmic but not nuclear events of the cell cycle in small Xenopus oocytes. AB - Microinjection of H-ras(val12) protein into fully grown Xenopus oocytes has been shown to induce meiotic maturation. In the present study, mRNA encoding the mutant ras protein was injected into both fully grown (stage 6) and growing (stage 4) oocytes. The mRNA induced nuclear breakdown in stage 6 oocytes, as expected. However, the mRNA induced neither nuclear breakdown nor maturation promoting factor when injected into stage 4 oocytes. Instead, the response in stage 4 oocytes included an activation pulse of calcium, cortical granule breakdown, elevation of the vitelline envelope, and abortive cleavage furrows, all of which are characteristics of the activation response in mature eggs. In addition, the injected mRNA led to increased rates of endogenous protein synthesis and the migration of subcortical organelles into the oocyte interior. These observations are discussed relative to the suggestion that oncogenic ras protein leads to an increase in both diacylglycerol and inositol trisphosphate, which then regulate the various cytoplasmic events described. PMID- 2098118 TI - [Nosocomial bacteremia caused by Acinetobacter]. AB - Forty episodes of nosocomial Acinetobacter calcoaceticus bacteremia produced by the Anitratus type over a period of 4 years were analyzed and compared with a control group of 28 patients with bacteremia produced by gram negative bacilli. Although most of acinetobacter bacteremia were endemic an outbreak involving 12 cases were observed in an intensive care unit during the study period. Thirteen patients presented a transient bacteremia. When the site of origin of the infection could be established the respiratory system was the most commonly involved (5 cases). Polymicrobial bacteremia was present in 11 patients (27.5%). Gram-positive cocci were the most commonly associated microorganisms. Most of isolated Acinetobacter strains were resistant to cotrimoxazole, beta-lactams, and aminoglycosides but were uniformly sensitive to ciprofloxacin and imipenem. The overall mortality was 22.5%. As compared with the control group, Acinetobacter bacteremia occurred more frequently during the first week of hospitalization and involved patients with less severe underlying diseases in whom three or more potential risk factors were detected. The entering site of infection was commonly unknown and the antibiotic treatment was inappropriate in most of the cases of Acinetobacter bacteremia. PMID- 2098119 TI - [Detection and antigenic distribution of hepatitis B virus in liver tissue and its relation to other serological markers of viral replication]. AB - The aim of this work has been the production of specific monoclonal antibodies against HBV-antigens and their utilisation in order to study their distribution on liver tissue. The monoclonal antibodies anti-HBc and anti-HBs were obtained by the modified hybridoma technique. This study was performed on 50 patients affected by several chronic hepatopathies. For the detection of the antigens, avidin-biotin-peroxidase complex immunostaining was used. Both cytoplasmic and membranous HBsAg were detected in 15 out of 16 HBsAg+ patients; 8 of 12 HBsAg /anti-HBc+ patients and 1 HBsAg-/antiHBc- patient. Cytoplasmic and nuclear HBcAg was observed in 12 of 16 HBsAg+ patients and 4 of 20 HBsAg- patients. Although the presence of serum HBsAg is an index of liver infection, in some HBsAg /antiHB+ patients (20%) with undetectable levels of HBsAg, hepatic injury may be disclosed by the detection of other markers of active viral replication. PMID- 2098120 TI - [Sternoclavicular staphylococcal arthritis in non-immunodepressed patients. Study of 4 cases]. AB - We report four patients (3 males and one female) suffering a sternoclavicular staphylococcal arthritis in whom risk factors such as parenteral drug addiction, alcoholism, diabetes, or immunosuppression were not observed. The etiopathogenesis, clinical picture, and diagnosis of this uncommon septic arthritis in reviewed. PMID- 2098121 TI - [Clinical importance of bacteremias caused by Acinetobacter calcoaceticus]. AB - Clinical data from patients with Acinetobacter calcoaceticus bacteremia observed during a period of 10 years were retrospectively reviewed. These bacteremias represent the 0.66% of the total number of positive blood cultures observed during the same period of time. The type anitratus was the most common (79.4%) although there were no significant differences in epidemiology, sensitivity, or clinical significance between both types. Only in 55.8% of the cases bacteremia was considered of clinical relevance. Multiple intravenous catheters represented the most important risk factor for bacteremia and site of infection origin (42%). Mortality in this series was about 30% of the cases. Contributions to the high mortality rate were the impossibility to establish an appropriate antimicrobial treatment in most of the cases and the existence of severe underlying diseases. The presence of immunosuppressive therapy or the existence of polymicrobial sepsis did not alter the prognosis. We conclude that once the presence of a blood culture positive to A. calcoaceticus is detected, antimicrobial treatment should be immediately established and investigation on the origin sites should be directed to the existing intravascular catheters. PMID- 2098122 TI - [Antimicrobial resistance of Haemophilus influenzae isolated outside of the hospital]. AB - A total of 209 H. influenzae strains isolated from follow-up patients were studied. Twenty eight strains were serotype b (13.4%), 82 corresponded to type I of Kilian (39.2%), and 41 produced beta-lactamase (19.6%). Strains were resistant to trimethoprim-sulfamethoxazole (SXT) in 79.9% of cases, to the erythromycin in 18.2%, to tetracycline in 16.7%, to chloramphenicol in 13.8%, and to cefaclor in 0.1% of instances. There were no strains resistant to cefotaxime nor to amoxicillin/clavulanic acid. Resistances to three or more antibiotics were observed in 14.8% of the strains. The most common of these combinations was ampicillin-chloramphenicol-tetracycline SXT (61.3%). PMID- 2098124 TI - [Ulcero-suppurative neck lesions]. PMID- 2098123 TI - [Environmental modulation of bacterial virulence]. PMID- 2098125 TI - [Lumbar tumors in a young woman]. PMID- 2098126 TI - [Confounding bias. Interaction]. PMID- 2098127 TI - [Empyema caused by Streptococcus equisimilis]. PMID- 2098128 TI - [Mono-microbial gangrene of the foot caused by Streptococcus agalactiae]. PMID- 2098129 TI - [Aortic endocarditis caused by Streptococcus equisimilis]. PMID- 2098130 TI - [Bacteremia caused by Streptococcus equisimilis in a neoplastic patient treated with recombinant interleukin 2]. PMID- 2098131 TI - [Bacteremias not detected by BACTEC NR 730]. PMID- 2098132 TI - [Syphilis in patients with HIV infection]. PMID- 2098133 TI - [Therapeutic implications of the identification of species within the genus Campylobacter]. PMID- 2098134 TI - [Antibodies against Borrelia burgdorferi in a population group from Valladolid]. PMID- 2098135 TI - [Screening]. PMID- 2098136 TI - [Fever, pain and functional impotence of the left elbow]. PMID- 2098138 TI - [Mesophile Aeromonas gastroenteritis: value of biotyping as virulence marker]. PMID- 2098137 TI - [Acute confusion syndrome and multiple intracranial lesions]. PMID- 2098139 TI - [Detection of chromosomal beta-lactamase hyperproduction]. PMID- 2098141 TI - [Corynebacterium jeikeium]. PMID- 2098140 TI - [Fusarium solani bronchopneumonia in a patient with acute myeloblastic leukemia]. PMID- 2098142 TI - [Clostridium septicum: a warning signal]. PMID- 2098143 TI - [Antibiotic prophylaxis before kidney transplantation]. AB - The effectiveness of antibiotic prophylaxis was evaluated in the immediate postoperative period of renal transplantation (RT). Before RT, the patients were randomly assigned to one of the following groups: 1) cefotaxime (intravenous infusion of 1 g one hour before the operation). 2) Ceftriaxone (1 g i.v. given in a similar way). 3) Control (without antibiotics). Patients who required antibiotic therapy during the first 3 postoperative weeks were excluded. 20 recipients of cadaveric renal grafts were included in each group. There were 39 males and 21 females with a mean age of 39.9 years. One patient from the cefotaxime group (5%), 2 from the ceftriaxone group (10%) and 2 from the control group (10%) developed infection of the surgical wound, all due to grampositive organisms. 19 patients had urinary tract infections: 7 from the control group (35%), 7 from the cefotaxime group (35%), and 5 from the ceftriaxone group (25%). The development of wound infection was not correlated with urea, creatinine, hemoglobin or total protein levels, or with urinary tract infection or fistula, diabetes or fever. The mean packed red cell volume of the patients who developed wound infection was 24.7 +/- 1.2 vs 28.6 +/- 6.6 in those who did not (p less than 0.01). All patients with visible hematoma and 3 of 10 with perirenal blood collection had wound infection. It was concluded that antibiotic prophylaxis for renal transplantation was useless in our patients. PMID- 2098144 TI - [Evaluation of methods for the detection of syncytial respiratory virus in nasopharyngeal secretions]. AB - The screening for respiratory syncytial virus (RSV) in nasopharyngeal secretions with enzyme immunoassay (ELISA) and indirect immunofluorescence (IIF) has been evaluated in infants and young children with acute respiratory infection. Both methods were compared with viral isolation in HEp-2 cells and the investigation of fluorescent foci in cell cultures inoculated by centrifugation. 226 samples were evaluated by IFF, 182 of which were also evaluated by ELISA while 158 were inoculated into cell cultures. 20.35% of samples were positive with IFF and 19.23% with ELISA. Isolation of RSV was obtained in 25 of the samples inoculated into HEp-2 cells (15.8%). The cytopathic effect took a mean of 5.4 days to develop. The investigation of fluorescent foci in centrifugated cultures allowed to detect 76% of positive samples 24 hours after centrifugation and 84% of positive samples 48 hours after it. Considering the viral isolation as the reference method, IIF and ELISA had a 88% and 76% sensitivity, respectively, with very similar specifities (90.2% and 91.7%). PMID- 2098145 TI - [Pneumocystis carinii pneumonia in patients with HIV infection at a Spanish hospital]. AB - Thirty cases of a first episode of Pneumocystis carinii pneumonia in patients with HIV infection were collected in a 32 month period. Most patients had long standing fever, cough and dyspnea. Laboratory findings were nonspecific. Remarkably, LDH activity was high in 88% of patients and the T4 lymphocyte count was lower than 200/mm3 in all patients in whom it was measured. Chest radiogram showed bilateral alveolar-interstitial pattern in 90% of cases. Bronchoalveolar lavage with ultracentrifugation was found to be the most effective diagnostic study, with 95% sensitivity. The frequency of secondary effects to cotrimoxazole which required to change to pentamidine was 13.3%. During hospital admission, 16.6% of the patients died, and the survivors had mortality rates of 4% and 85% after 3 and 20 months, respectively. PMID- 2098146 TI - [Corynebacterium jeikeium septicemia]. AB - An adult male with non-Hodgkin lymphoma, who had been admitted to the hospital for more than one month and had received previous antibiotic therapy, developed Corynebacterium jeikeium septicemia. The organism was isolated in four blood cultures and it was multirresistant, being only sensitive to vancomycin, ciprofloxacin, norfloxacin and rifampin. The patient improved clinically and was bacteriologically cured with intravenous vancomycin therapy. PMID- 2098147 TI - [In vitro sensitivity to 5-fluorocytosine and amphotericin B of yeasts of the Candida genus isolated in Barcelona]. AB - In 200 strains of Candida sp, 38.5% were found to have intermediate sensitivity or to be resistant to amphotericin B and/or 5-fluorocytosine by the agar diffusion method. When the minimal inhibitory concentrations of these strains were measured, only 7.8% were resistant to amphotericin B and 2.8% to 5 fluorocytosine. The species with the highest levels of resistance were C. parapsilosis, C. tropicalis and Torulopsis glabrata. Candida albicans did not show resistance to 5-fluorocytosine. PMID- 2098148 TI - [The use of antimicrobials in renal insufficiency]. PMID- 2098149 TI - AIDS in the brain. PMID- 2098150 TI - Serological perspectives on hepatitis B and D. PMID- 2098151 TI - HIV-1 infection in HIV-1 enzyme-linked immunoassay seronegative patients in Kinshasa, Zaire. AB - Serum samples of 62 African patients who had clinical manifestations of HIV-1 infection but were seronegative for HIV-1 by ELISA (Organon) were subsequently further tested by another HIV-1 ELISA test (Wellcozyme), HIV-1 IgG Western blot, HIV-1 antigen detection and HIV-2 ELISA. Patients' lymphocytes were cultured for HIV-1 and 2. Because of limited quantities of serum available all tests were not performed on all samples. Seven (26%) of 27 sera of patients meeting the WHO clinical case definition of AIDS were Western-blot-positive. In contrast, of 35 patients' sera with possible HIV related disease, only one (3%) was Western blot positive (P = 0.02) and none of 75 sera from HIV-1 ELISA (Organon) seronegative blood donors (P less than 0.01) were Western blot positive. Of 30 HIV-1 ELISA (Organon) seronegative patients tested with the HIV-1 ELISA Wellcozyme assay only one was seropositive (this patient's serum was also Western blot positive). Of 17 HIV-1 ELISA (Organon) seronegative patients tested, HIV-1 antigen was found in 1 case (6%) (this patient's serum was Western blot negative). None of the 34 patients tested by HIV-2 serology was HIV-2 seropositive. HIV-1 was isolated by culture in 3 (21%) of 14 HIV-1 ELISA seronegative patients (sera of the 3 patients were Western blot negative). In total, 12 (19%) of 62 HIV-1 ELISA (Organon) seronegative patients were found to be positive for HIV, either by Western blot HIV antigen testing or viral culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098152 TI - AIDS education in rural Uganda--a way forward. AB - A survey of acquired immunodeficiency syndrome (AIDS)-related knowledge and attitudes was conducted during July and August 1988 in rural SW Uganda. The aim was to assess the impact of Uganda's AIDS education programme and to consider how future programmes could be more effectively implemented. Four hundred and seventy six individuals aged 12-45 years were selected by a quota method, to form a sample stratified by age and sex. Mass AIDS education has successfully raised levels of knowledge but misconceptions persist. However, it has failed, firstly, to stress the urgency of AIDS as a personal issue, and secondly, to change negative attitudes toward people with AIDS: 57% would avoid or stigmatise an individual with AIDS. Unexpectedly, findings show that a correlation exists (P less than 0.05) between high levels of 'correct' beliefs and negative attitudes toward people with AIDS. To achieve future behavioural and attitude changes, possible ways forward for Ugandan AIDS education include involvement of HIV carriers in education, small-scale targetted approaches developed by active participation of the target group and through role playing of people with AIDS. PMID- 2098153 TI - Performance of Chlamydiazyme enzyme immunoassay for detecting Chlamydia trachomatis in cervical specimens. AB - Two aspects of the performance of Abbott's improved Chlamydiazyme enzyme immunoassay (EIA) were studied. Firstly, the test was compared with cell culture in cervical specimens from 100 abortion applicants. The results showed good correlation between the two methods, with 12 women positive with both methods and one woman EIA-positive but culture-negative. Compared with cell culture the EIA had sensitivity of 100% and specificity of 98.9%. Secondly, the reproducibility of positive EIA tests was evaluated by re-analysing 100 consecutive positive specimens. Ninety-nine of these remained positive and one weakly positive specimen became negative. There was close correlation between absorbance values on first and second analyses. The performance of the Chlamydiazyme EIA in terms of sensitivity, specificity and reproducibility is acceptable in this patient population. PMID- 2098154 TI - Setting up a support service for male prostitutes in London. AB - Estimating the number of male prostitutes working at any given time is fraught with difficulties. We suggest that perhaps around 600-700 men were selling sex in London in 1989. We report some preliminary observations gained during the setting up of a specific service for male prostitutes. Of 32 male prostitutes seen, 26 worked as rent-boys, 4 worked through agencies and 2 worked independently from home. Forty-one per cent had evidence of at least one sexually transmissible disease and 3 of 16 men tested (19%) were human immunodeficiency virus (HIV) positive. PMID- 2098155 TI - Epidermoid cyst of the testis. PMID- 2098156 TI - Sexually transmitted diseases and rape. PMID- 2098157 TI - Single-dose fluconazole in the treatment of Candida albicans balanoposthitis. PMID- 2098159 TI - AIDS Literature Index. PMID- 2098158 TI - Goals and objectives for STD/AIDS control into the 1990s. PMID- 2098160 TI - Using the forward traction headgear (facemask). 2. PMID- 2098161 TI - Informed consent--an essential part of orthodontic records. PMID- 2098162 TI - Fixed appliance without ligatures. PMID- 2098163 TI - Case report: Class I with open bite and bimaxillary protrusion. PMID- 2098165 TI - Locus of control and drinking behavior in American Indian alcoholics and non alcoholics. AB - Many investigators have attempted to determine whether alcoholics differ from non alcoholics in their perceived locus of control. The present study examined the responses of alcoholic and non-alcoholic American Indian males and females on Levenson's Multidimensional Locus of Control Scale. Subjects were 80 American Indian males and 40 American Indian females. All subjects were members of either an eastern (Cherokee) or western (Cheyenne) Oklahoma tribe. Results indicate no significant differences between the Cherokee male alcoholic and non-alcoholic group. Cheyenne male alcoholics reported significantly lower internal control scores than did Cheyenne male non-alcoholics. Within the female sample, alcohol use and tribal membership showed a significant interaction with locus of control. These findings suggest that locus of control may be a potentially useful clinical construct in the development of treatment plans and therapeutic issues for American Indian patients who are alcoholics. PMID- 2098166 TI - Psychiatric function and roles in an Indian health program context. AB - This paper relates the experience of a non-Indian psychiatrist who successfully functioned in an urban Indian health care setting. It illustrates the process of becoming a part of a mental health team and the complexities of becoming a culturally-sensitive psychotherapist. This is accomplished by relating personal experiences, observations, case examples and self-questioning of therapeutic roles and functions. The author concludes that a psychiatrist should not rigidly define his or her role upon entering a particular setting but instead should allow a multitude of roles to unfold. Psychiatrists are also urged to remain constant students of the culture of the patients and organization, applying that knowledge as dictate by the treatment situation. PMID- 2098164 TI - Case report: an adult with mandibular crowding and crossbite and impacted maxillary cuspids with cyst. PMID- 2098167 TI - Ojibway adolescent time spent with parents/elders as related to delinquency and court adjudication experiences. AB - This study sought to determine whether volume of time spent by adolescents (ages 12-18) with their families (parent/elder present) and the existence of family dysfunctional factors (substance use, domestic abuse, and negative well-being within the family) shared a relationship with adolescent experience in court adjudication and juvenile delinquency behaviors. Results indicated that adolescents experiencing greater volume of family contact tended to have less involvement with both court adjudication and delinquency behaviors (r = -.16 to .38). Increased frequency of family dysfunctional factors served as a predictor of adolescent involvement with court adjudication and juvenile delinquency (r = .24 to .59). PMID- 2098168 TI - The persistence of traditional medicine in urban areas: the case of Canada's Indians. AB - The persistence of the traditional medical systems among Canadian Native peoples has been fairly well documented, and some commentators have suggested that a resurgence in these systems is currently underway (Gregory, 1988). Although there have been very few studies of the utilization of these medical systems by contemporary Native peoples, there has been some suggestion that dual utilization is indeed practiced. Virtually nothing is known about the specific patterns of utilization, and the relationship, if any, between the utilization of traditional and western medical services. Similarly, few aspects of health care utilization by Native peoples in urban areas have been researched. The purpose of this paper is to explore this relationship through the examination of data obtained in a recent study of Native and non-Native medical service utilization patterns in the city of Saskatoon, Saskatchewan. PMID- 2098169 TI - Application and comparison of techniques for three-dimensional analysis of craniofacial anomalies. AB - Traditionally, cephalometric analysis has been limited to data determined from two-dimensional (2-D) cephalograms. With imaging facilities such as CT and biplanar radiography now available, the natural extension has been towards the use of three-dimensional (3-D) coordinate positions of landmarks for comparative purposes. While these data have been potentially available for several years, the accurate and reproducible extraction of anatomic landmarks suitable for comparative purposes has been limited. This paper presents results of the application of traditional comparative techniques to well determined 3-D coordinate data acquired from biplanar radiography and CT for a patient with Treacher Collins syndrome and further provides a comparison with the technique of strain analysis, often referred to as finite element analysis, which has been applied recently to craniofacial data. Comparisons of distances and angles between landmarks, landmark coordinate positions, and strains of the patient relative to experimental reference standards reveal that the essential skeletal features of Treacher Collins syndrome have been identified and quantified by the analysis techniques. Further, a measure of the significance of the deviations has been determined by comparisons with the experimental reference standards. PMID- 2098171 TI - Remodeling techniques for immature and mature cranial vault bone: technical note. AB - Remodeling cranial vault bone requires age-dependent technique modifications. Cranial vault bone, in children less than 1 year of age, remodels, readily using radially oriented osteotomies. In children older than 1, however, the bone is relatively brittle, yet it, too, may be remodeled by sectioning it first into 1.5 to 2.0 cm wide strips, then placing resistance-weakening kerfs on the bone's endocranial surface. The kerfs weaken the bone regionally so that controlled bending may occur. PMID- 2098170 TI - Cementoma--presentation predicates approach. AB - Cementomas are benign jaw tumors that originate from periodontal ligament elements. Four classifications of cementomas are described: periapical fibrous dysplasia, benign cementoblastoma, cementifying fibroma, and florid osseous dysplasia. Usual treatment regimens vary from observation to limited surgical resection based upon tumor type and clinical characteristics. We present an unusual case report of an extensive cementifying fibroma that required mandibular and inferior alveolar nerve resection followed by osseous and neural reconstruction. PMID- 2098172 TI - Development of synthetic bone-repair materials for craniofacial reconstruction. AB - In an effort to minimize problems associated with use of bone grafts and bank bone for craniofacial reconstruction, synthetic biodegradable alternatives are under development at the U.S. Army Institute of Dental Research. The focus is on composite materials in which either d,l-polylactide co-glycolide or porous tricalcium phosphate function as degradable delivery systems for bone-inductive proteins. Availability of synthetic bone-repair materials would eliminate the need for invasive graft-harvesting procedures, the dangers of pathogen transmission from, and immunogenic reaction to bank bone. In addition, synthetics should be more easily sculpted to restore facial contours. Elimination of the disadvantages of natural bone grafts would result in improved reconstructive care for victims of trauma, disease, and congenital deformity. Military surgeons can especially appreciate the potential of a convenient synthetic bone replacement for use in mass casualty situations where access to, and storage facilities for natural bone will be extremely limited. This review updates current treatments and requirements for synthetic bone-repair materials and describes several experimental materials under evaluation at the U.S. Army Institute of Dental Research. PMID- 2098173 TI - Growth and differentiation factors: role in bone induction and potential application in craniofacial surgery. AB - Repair of craniofacial bone often requires autogenous or allogeneic bone. Natural materials deliver bone-inducing substances to wound beds and provide scaffolding for osteoconduction, but not without risk of morbidity. We are developing a synthetic material consisting of proteins which stimulate bone repair encased within a moldable, biodegradable delivery system. The stages of bone induction include chemoattraction of stem cells, proliferation and differentiation of these cells to competent chondrocytes and osteoblasts, angiogenesis, mineralization, and remodeling. Bovine osteogenin induces bone formation in soft tissue in rats, and accelerates bone repair in cranial defects. The protein has been purified and partially sequenced. Growth factors may augment the inductive effects of osteogenin by attracting preosteoblasts, accelerating their proliferation, and stimulating angiogenesis. A composite material of osteogenin and growth factors released from a biodegradable delivery system in a time-dependent fashion is proposed to decrease the necessity for autogenous and allogeneic bone implants. PMID- 2098174 TI - Neuropsychologic outcome after craniofacial fracture. AB - Forty eight patients with facial fractures resulting from trauma were admitted to a Plastic Surgical Unit. The fractures were treated on standard lines and ten of the patients required craniotomy for CSF rhinorrhea or repair of depressed frontal fractures. Neuropsychologic assessment was carried out on all patients approximately 17 months after the initial injury. An assessment of the extent to which the trauma had affected the personality and social adjustment of each individual was also carried out at that time. In four patients there was no evidence of any neuropsychologic impairment on any of the tests administered. The neuropsychologic deficits were most noticeable in those who had suffered a cranial fracture. In patients with facial fractures but no evidence of cranial fractures, there was no association between neuropsychologic impairment and site of injury. Loss of consciousness was associated with poor social adjustment and a marked change in personality. The best predictor of subsequent neuropsychologic deficits and social maladjustment was found to be the Glasgow Coma Score at the point of admission to the hospital after injury. It is concluded that with this type of injury careful neuropsychologic assessment is important in identifying the subtle deficits that might otherwise remain undetected. PMID- 2098176 TI - Pseudomeningocele as a complication of teratoma resection and aseptic meningitis following craniofacial reconstruction: a case report. AB - This is a report of two extremely unusual complications of craniofacial surgery on a single patient. A 14-year-old female underwent resection of a recurrent teratoma four times within the first 9 years of life. This left her with two large cranial cavities in the left temple and posterior to the orbit communicating with the subarachnoid space constituting a pseudomeningocele and pulsatile mass in the left temple--an unusual complication. Following resection of the pseudoepithelial cavity linings, the spaces were filled with a split temporalis muscle. Two weeks following surgery, she developed signs and symptoms of meningitis with negative cultures from the drain sites and lumbar puncture. Six days following an unsuccessful attempt to treat her with wide spectrum antibiotics, she was treated with dexamethasone. As a result, there was a dramatic disappearance of signs and symptoms in less than 36 hours; she has not experienced any recurrence since. We feel that this aseptic meningitis was the result of cerebrospinal fluid exposure to muscle--a rare, yet, previously reported complication. The details of the case history and discussion of complications and the way in which they can be avoided, are subjects of this report. PMID- 2098175 TI - Sequencing LeFort fracture treatment (Organization of treatment for a panfacial fracture). AB - The types of midfacial fractures and their complexity were evaluated in admissions to the Maryland Institute of Emergency Medical Service Systems (MIEMSS) during the years of 1984 to 1988. Two hundred and sixty-eight LeFort fractures were treated and followed (3.2 percent of admissions). One half (50 percent) had skull fractures and 40 patients (15 percent) had LeFort, skull and mandibular fractures. Isolated nasoethmoidal fractures were observed in 176 patients and in 107 patients (39 percent) of patients with LeFort fractures. Isolated mandibular fractures were observed in 321 patients and in 104 patients with LeFort fractures (39 percent). Eleven percent of patients had midfacial, nasoethmoidal and frontal sinus fractures. Six percent of patients had midfacial, frontal bone, frontal sinus and nasoethmoidal fractures (Cranial Base Crush Syndrome). Twenty two percent of patients had LeFort and frontal sinus fractures. Reconstruction of multiple area injuries is simplified by a highly organized treatment sequence that conceptualizes the face in two groups of two units. Each unit is divided into sections, and each section is assembled in three dimensions. Sections are integrated into units and units into a single reconstruction. Conceptually, in each unit, facial width must first be controlled by orientation from cranial base landmarks. Projection is then (and often reciprocally with width) established. Finally, facial length is set both in individual units and in the upper and lower face. Soft tissue is considered the "fourth dimension" of facial reconstruction. Bone reconstruction should be completed as early as possible to minimize soft tissue shrinkage, stiffness and scarring of soft tissues in nonantomic positions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098177 TI - Septopremaxillary ligament resection and midfacial growth in a chimpanzee animal model. AB - Data collected from human studies suggests a relationship between a disruption of the septopremaxillary ligament (SPL) attachment and midfacial hypoplasia in complete cleft individuals. The present study investigates the SPL-traction mechanism and midfacial growth in a chimpanzee animal model. Seventeen chimps (7 unoperated controls, 5 shams, and 5 animals with early SPL reaction) were used in the present study. Lateral head x-rays and dental study models were collected quarterly through 1200 days of age. Growth rates (slopes of the linear growth components) were statistically compared across groups. Premaxillary growth rates were significantly (p less than 0.001) reduced in SPL resected animals compared to the other groups. Maxillary growth rates were significantly reduced in both SPL and sham animals compared to unoperated controls. No significant differences were noted for midfacial height. We conclude that SPL resection produced a significant effect on anterior midfacial growth independent of surgical trauma. These data support the concept of early reestablishment of the SPL in primary nasolabial cleft repair. PMID- 2098178 TI - Exploration of the orbital floor: an indicated procedure? AB - Fractures to the middle third of the facial skeleton continue to increase in frequency secondary to motor vehicle accidents and interpersonal violence. Orbital floor fractures can occur either independently or may be associated with other facial bone fractures. Controversy has persistently surrounded the treatment of fractures to the floor of the orbit. We will present our investigation of 296 patients who sustained a total of 396 traumatic injuries to the orbit and were treated at the University of California, Davis Medical Center, Sacramento, California, during the period July 1, 1988 to June 30, 1989 to determine whether surgical exploration of the orbital floor is necessary or adds potential serious risks. In the 38 patients (46 orbits) who did not undergo surgical exploration of the orbital floor, 31 (82%) suffered serious residual complications. In the remaining group of 258 patients who underwent orbital floor exploration, there was a 7 percent incidence (18 patients) with residual sequelae. We conclude that exploration of the orbital floor has the potential to decrease the incidence of serious post-traumatic complications significantly, primarily enophthalmos. PMID- 2098179 TI - Effects of material porosity on implant bonding strength in a craniofacial model. AB - Alloplastic craniofacial implantation is a developing surgical option. Several alloplastic materials are available with a porous feature. While porosity may permit bone ingrowth, it is unclear whether it offers improved implant fixation over that of nonporous bone substitutes in the craniofacial skeleton. Bilateral mandibular ramus defects were created and reconstructed with porous and nonporous block implants in the mature rabbit. At 3, 6, and 12 months postoperatively, the mandibles were removed and prepared so that only the bone-implant interface connected the proximal and distal segments. The anterior mandible was then loaded to destruction. The fatigue load (in kg) for each implant was obtained and statistically compared. Significant differences in fatigue loads between the implant types occurred at all postoperative periods with the porous block material consistently exhibiting the greater resistance to separation. Resistance to fatigue fracturing for either implant type did not increase after the sixth postoperative month. PMID- 2098180 TI - Treatment of craniofacial meningiomas. AB - A series of 54 patients with craniofacial meningiomas were treated at the Burdenko Neurosurgical Institute in Moscow between 1978-1988. The peculiarities of diagnosis and surgical treatment of these neoplasms are the basis of this presentation. PMID- 2098181 TI - Botulinum toxin. AB - The National Institutes of Health Consensus Development Conference on Clinical Use of Botulinum Toxin brought together neurologists, ophthalmologists, otolaryngologists, speech pathologists, and other health care professionals as well as the public to address: the mechanisms of action of botulinum toxin, the indications and contraindications for botulinum toxin treatment, the general principles of technique of injection and handling for its safe and effective use, and the short-term and long-term side effects and complications of therapy. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel recommended that (1) botulinum toxin therapy is safe and effective for treating strabismus, blepharospasm, hemifacial spasm, adductor spasmodic dysphonia, jaw-closing oromandibular dystonia, and cervical dystonia; (2) botulinum toxin is not curative in chronic neurological disorders; (3) the safety of botulinum toxin therapy during pregnancy, breast feeding, and chronic use during childhood is unknown; (4) the long-term effects of chronic treatment with botulinum toxin remain unknown; and (5) botulinum toxin should be administered by committed interdisciplinary teams of physicians and related health care professionals with appropriate instrumentation. The full text of the consensus panel's statement follows. PMID- 2098182 TI - Cervical spine palpation. PMID- 2098183 TI - Effect of changes in the relationship of the mandible to the maxilla on the dimensions of the external acoustic meatus. AB - A preliminary study of seven randomly selected subjects was initiated to assay if any changes occur in body posture and in the dimensions of the external acoustic meatus when the relationship of the mandible to the maxilla is changed. The anatomic configurations presented by body posture and the external acoustic meatus, when the mandible was in a position of intercuspation, were used as points of reference. The dimensions of body posture and the external acoustic meatus were recorded for all subjects, when their respective mandibles were in intercuspation, protrusive, retrusive, as well as a position produced by orthopedic splints. Although, the position of intercuspation was used as a point of reference, comparisons of results obtained by all positions used, were made. Changes in the dimensions of body posture and the dimensions of the external auditory meatus were noted with every one of the prescribed alterations of mandibular posture. PMID- 2098184 TI - Correction of mandibular asymmetry with the ligated anterior repositioning splint. AB - Mandibular asymmetry may be the result of unequal ramus height, unequal corpus length, or a combination of both problems. The diagnosis of asymmetry is essential in treatment planning, since a number of therapeutic options must be considered in the treatment to a seated condylar position in the glenoid fossa. When asymmetry exists, it may be necessary to: accept finished treatment with the mandibular midline to the right or left of the maxillary midline, finish the molars and canines in an end-to-end relationship on the short side, treat with asymmetric extractions, intervene surgically, or use functional appliances to enhance greater growth or remodeling of the mandible on the short side. The purpose of this study was to assess the effect of the ligated anterior repositioning splint, or LARS, in the correction of mandibular asymmetry in Class II patients. PMID- 2098185 TI - Prosthodontic management following craniomandibular pain and dysfunction therapy: a review of the literature. AB - Much of the literature on craniomandibular joint (CMJ) dysfunction-pain (previously called temporomandibular joint (TMJ) dysfunction-pain) is focused on the etiology and treatment of symptoms, with little discussion of finalization procedures. Craniomandibular disorders encompass a broad range of patient complaints, and the therapies used for these symptoms include an entire spectrum of treatment modalities. Following successful therapy in Phase I, the problem facing the dentist is how to finalize treatment. This paper is a review of the literature on Phase II management including rationale, principals, and methods of stabilizing and rehabilitating the occlusion, emphasizing the prosthodontic perspective. PMID- 2098186 TI - Chronic TM disorder and non-TM disorder pain: a comparison of behavioral and psychological characteristics. AB - The purpose of this paper is to determine whether patients with chronic temporomandibular disorder (TMD) pain manifest behavioral, experimental, and psychological characteristics similar to patients with other chronic pain illnesses. The Chronic Pain Battery (CPB), a multidimensional assessment tool for chronic pain patients, was used to compare several important variables between 78 TM disorder (TMD) patients and 98 non-TMD chronic pain patients. The study found that chronic TMD patients had lower "usual" pain intensity and suffering levels, fewer vegetative symptoms associated with depression, higher pain tolerance, less impairment of activity, more hope about treatment outcome, lower health care system utilization, but higher reported stress levels than non-TMD chronic pain patients. The two groups manifested no significant differences in use of narcotics, sedatives, and sleeping pills; levels of depression, anxiety, somatization, hostility, or psychoticism; illness behavior reinforcement in their social surroundings; or ratings of problems with work, family, self-esteem, or suicidal impulses. These findings suggest that chronic TMD pain patients (with a symptom duration of over six months) are behaviorally and psychologically similar to non-TMD chronic pain patients, but that they differ in their perceptions of their disorder, rendering them less handicapped by their problems. Psychological, social, and behavioral treatment methods useful for treating chronic pain syndrome may thus also be applied along with dental therapy for optimal treatment of TMD associated with chronic pain. PMID- 2098187 TI - Investigations on prevalence and treatment of fingernail biting. AB - Numerous investigations indicate that there is a parallel between emotional stress and hyperactivity of the masticatory muscles connected with mandibular parafunctions. Elimination of mandibular parafunctions is difficult and almost impossible, therefore, this paper proposed a treatment whereby nonharmful motor habits are substituted for the parafunction. Questionnaire investigations were carried out in 2905 subjects, with an attempt at treatment in the youngest group of 222 pupils. It was found that good results were obtained through adult supervision and cooperation. PMID- 2098188 TI - Assessment and treatment of TMJ muscles, fascia, ligaments, and associated structures. AB - The primary goal of temporomandibular joint therapy is to establish normal physiologic tension of the muscles, fascia, ligaments, and associated soft tissue structures. Because of pathologic sprain and strain patterns in the TMJ structures, the patient may exhibit pain and dysfunction due to tissue tightness, disk displacement, and occlusal discrepancies. This article presents an effective clinical technique to assess and relieve the sprain and strain in the TMJ muscles, fascia, ligaments, and associated structures to restore normal physiology. PMID- 2098189 TI - Trigeminal neuralgia: treatment failure with auriculotherapy: two case reports. PMID- 2098190 TI - Standards for the history, examination, diagnosis, and treatment of temporomandibular disorders (TMD): a position paper. American Academy of Head, Neck and Facial Pain. PMID- 2098191 TI - Interrelationship of internal derangements of the temporomandibular joint, headache, vertigo, and tinnitus: a survey of 25 patients. AB - Twenty-five patients presenting with a chief complaint of pain around the temporomandibular joints, along with symptoms of internal derangements, i.e., clicking or crepitus, and concomitant vertigo were treated successfully with jaw repositioning orthotics. All had been examined by physicians for otalgic disorders and were considered negative. Vertigo was remitted with orthotic therapy in all cases and returned with the removal of the appliance. Anatomic and physiologic hypotheses are presented as potential etiologies. PMID- 2098192 TI - Comparison of three clinical techniques for evaluating joint sounds. AB - Two-hundred two consecutive adult patients presenting to the University of Kentucky for general dental care screening were examined for temporomandibular joint sounds by three techniques: (1) lateral pole surface palpation, (2) digital palpation in the external auditory canal, (3) auscultation by a stethoscope. Sixty-nine patients reported joint sounds, but only 32 had sounds diagnosed by auscultation resulting in a 54% false-negative reporting rate. Stethoscopic auscultation was used as the standard to which the other two techniques were compared. The false-negative rate for auditory canal digital palpation was 71% and 77% for lateral pole surface palpation. Surface palpation had only a 2% false positive incidence while auditory canal digital palpation had a 51% false positive rate. There was poor agreement between the patients' subjective reporting and clinical exam by any technique. Using stethoscopic auscultation as the standard, both auditory canal and surface palpation had a very high false negative rate, but only the auditory canal palpation had a poor false-positive incidence. Auditory canal palpation often produces TMJ sounds that are not heard with a stethoscope during normal opening and closure. PMID- 2098193 TI - Occurrence of temporomandibular disorder symptoms in healthy young adults with and without evidence of bruxism. AB - Few studies have specifically examined the association between bruxism and symptoms of temporomandibular disorders in adults. In this study 569 freshmen dental students entering the Medical College of Georgia over a 10-year period completed an 18-item "yes/no" questionnaire relating to awareness of tooth clamping/clenching/grinding and signs and symptoms of oral, facial, and craniomandibular discomfort, pain, and disorders. A higher proportion of females than males reported that they were aware of clamping and clenching their teeth, as well as symptoms of stiff jaw, sore jaw or teeth, cracking or locking jaw joint, and headaches in the morning. Reported awareness of tooth clamping and clenching and of someone having heard tooth grinding was significantly associated with reported pain, discomfort, or other sensations in, in front of, or behind the ear in the overall subject group. PMID- 2098194 TI - Etiologies of tic douloureux: trigeminal neuralgia. AB - Tic doloreaux, commonly known as trigeminal neuralgia, has bewildered researchers for hundreds of years as to the exact etiology of its pain mechanisms. Due in large part to the intense nature of the tic-like pain, this disease has drawn a lot of attention. Two divergent viewpoints, central verses peripheral, provide insight into possible mechanisms. This paper provides an overview of the different theories postulated as the causative factors so that the practitioner may better be able to diagnosis and treat the syndrome. PMID- 2098195 TI - Study of mandibular movements during speech. AB - We recorded the mandibular movements produced during the reading of a text, in Spanish, using a kinesiograph in a random sample of 71 people aged 24 to 35. In each recording we measured nine variables and did a descriptive analysis of each variable. Our findings support that the mandibular movement during speech has some definite characteristics. The most important fact is that it could be a high percentage of occlusal contacts at incisal level during speech. This has to be taken into account when exploring an occlusal trauma of unknown etiology. PMID- 2098196 TI - Cervicogenic headache differential diagnosis and clinical management: literature review. AB - The diagnosis and treatment of patients experiencing head and neck pain is a difficult task for any clinician who pursues this area. The purpose of this paper is to elaborate upon a unilateral headache which is referred to as cervicogenic headache. The literature provides strong evidence demonstrating the relationship of the cervical spine and the possibility of referral pain to the head and facial areas. PMID- 2098198 TI - Diagnosis and treatment of TMJ, head, neck and asthmatic symptoms in children. AB - The normal physiologic tension of the TMJ muscles, fascia, ligaments, and associated structures is critical for the health of children. Pathologic strain patterns in the soft tissues can be a primary cause of headaches, neckaches, throat infections, ear infections, sinus congestion, and asthma. This article presents effective diagnostic and treatment modalities from both dental and physical therapy viewpoints to relieve and restore normal physiology to the TMJ muscles, fascia, ligaments, and associated structures. As structural balance is restored, a nutritional component of therapy is strongly recommended for the child's optimum health. PMID- 2098199 TI - Manual reduction of displaced disk. AB - Early use of manual disk reduction procedures was significant in providing a functional disk-condyle relationship. Ninety-three percent of the 41 patients with anterior medial displaced disk without recapture did not require surgical correction using manual disk reduction procedures. All reductions were done within a six- to eight-week time period from the date of onset. PMID- 2098197 TI - Lateralization of chronic facial pain: fact or fiction. AB - Previous studies have shown that pain is generally reported more on the left side of the body. It has been hypothesized that patient report of left pain dominance may be due to the right hemisphere being less efficient in processing cutaneous sensory input while being dominant for emotional experience as compared with the left hemisphere of the brain. Only in cases of trigeminal neuralgia has self report of pain been lateralized to the right side. Due to previous research findings, we postulated that other facial pain diagnoses may demonstrate a right sided dominance due to the lack of neural crossover in the facial region. The results of the study found no significant difference between self-report of right and left-sided facial pain within four diagnostic categories. It was concluded that the results of right lateralized pain with trigeminal neuralgia should not be generalized to the facial pain population as a whole. PMID- 2098200 TI - [New analgesically active derivatives of 1-phenyl-5-mercaptotetrazole]. AB - For the investigation of new anti-inflammatory drugs, 1-phenyl-5 mercaptotetrazole (I) was selected as the principal structure. The purpose itself lay in an alkylation of the mercapto group with different remainders. In some cases at the same time a substituent was introduced on the phenyl nucleus in position 1. An alkylation of 1-phenyl-5-mercaptotetrazole with ethyl bromacetate and a subsequent hydrolysis resulted in (1-phenyl-5-tetrazolylthio)acetic acid (II) as well as its chloride and hydrazide. The reaction of chloride with amino acids gave rise to amides III-VII. From hydrazide and phenylisocyanate, 4 chlorphenylisocyanate and phenylisothiocyanate, semicarbazides VIII and IX and thiosemicarbazide X were prepared. Furthermore, a reaction of substituted anilines and 2,3-expoxypropylchloride yielded the pertinent 3-anilino-2 hydroxypropylchlorides XX-XXIII, by which 1-phenyl-5-mercaptotetrazole in the form of the potassium salt was alkylated to compounds XIV-XIX. 1-Phenyl-5 mercaptotetrazole was also alkylated by 2-chlorethanol and the obtained 1-phenyl 5-(2-hydroxyethylthio)tetrazole was esterified by 4-phenylbenzoylchloride and 2 acetoxybenzoyl-chloride giving rise to esters XII and XIII. Finally, three compounds XXIV-XXVI, resulting from an alkylation of 1-phenyl or 1 allylmercaptotrazole by substituted 3-phenoxy-2-hydroxypropylchlorides. In all compounds an orientational acute toxicity higher than 1 g/1 kg p.o. was found. Pharmacological results are shown in Table 2. None of the above-mentioned compounds showed a significant anti-inflammatory efficacy. Analgetic efficacy was manifested in a more marked way; in compound VIII it is comparable with the used standard aminophenazone. PMID- 2098201 TI - [In vitro evaluation of antibacterial activity of the original oxime type of beta lactam antibiotics with the 4-aminobenzensulfonamide group]. AB - Four newly prepared beta-lactam antibiotics of the oxime type with a 4 aminobenzensulphonamidogroup, synthetized at the Research Institute for Pharmacy and Biochemistry, Prague, were subjected to an evaluation of antibacterial efficacy in vitro. The evaluation was carried out by determining the minimal inhibitory concentration (MIC) in 47 clinical strains and 6 standard strains (Staphylococcus aureus, Streptococcus pyogenes and facecalis, E. coli, Enterobacter and Proteus spec., Pseudomonas aeruginosa). The results were compared with the MIC of cefalexin, cefoxitin, cefazolin, cefsulodin, and ampicillin. The antibacterial effect of these agents was lower than that of the compared antibiotics. It was slightly better in the pseudomonadic strains, where the efficacy of cefusulodin was best and the other four antibiotics appeared to be worst. PMID- 2098202 TI - [In vitro antibacterial activity of new oxime type of beta-lactam antibiotics]. AB - The antibacterial efficacy of two novel beta-lactam antibiotics of the oxime type, VUFB 16265 and 16272, was evaluated by determining the minimal inhibitory concentration (MIC) in 47 clinical strains and 6 standard strains (Staphylococcus aureus, Streptococcus pyogenes and faecalis, E. coli, Enterobacter and Proteus spec., Pseudomonas aeruginosa), which were the most frequent causes of infectious complications. The results were compared with the MIC of cefalexin, cefoxitin, cefazolin, cefsulodin, and ampicillin. The antibacterial activity of both VUFB drugs was comparable with the efficacy of the antibiotics tested. Only in the strains of Pseudomonas aeruginosa the activity of all antibiotics under evaluation was low and only cefsulodin was effective. PMID- 2098204 TI - Development of a method of continuous temperature measurement for microwave denture processing. AB - A method of continuously measuring temperature during microwave irradiation was developed using a metal sheathed thermocouple. The temperatures recorded by this method were compared with those measured intermittently with a mercury thermometer. Samples of Sydney tap water (50 ml) were heated using a domestic microwave oven at High and Low powers which were the maximum (500 W) and minimum (50 W or 10%) powers of the oven, respectively. At 500 W, boiling was seen to occur within 1 min and the measurement with the mercury thermometer was omitted. The continuous temperature measurement with the thermocouple showed that the boiling point was reached at about 45 s. At 50 W the 10% work was shown by the delivery of 3 s microwave radiation which was repeated every 32 s. The boiling point was recorded at about 6 min, which was much earlier than the time (10 min) noted visually. The boiling point could not be registered with the mercury thermometer method. Visual observation or intermittent temperature measurement can result in an underestimation of temperature reached during microwave irradiation. PMID- 2098203 TI - [Determination of sulbactam in human serum using capillary isotachophoresis]. AB - A method of determination of sulbaktam in human serum by capillary isotachophoresis with the use of a conductivity detector was worked out. Prior to the proper analysis, a pretreatment of the sample of serum was carried out by extracting sulbaktam to butyl acetate. The total yield of the proposed analytical procedure with an extraction first stage approaches 94%. The smallest determinable amount of the sample corresponds to 1 micrograms of sulbaktam in 1 ml of serum. The reported method was employed to evaluate the samples of sera of volunteers after intravenous administration of the dosage form sulbaktam ampicillin (VUFB) and the foreign pharmaceutical preparation Unasyn (Pfizer). Statistically insignificant differences in pharmacokinetic parameters have confirmed that the preparations are highly bio-equivalent. PMID- 2098205 TI - Changes in NMR chemical shifts of methacrylates induced by their interactions with the phospholipid and the phospholipid/cholesterol liposome system. AB - The interaction of methyl methacrylate (MMA), ethylene dimethacrylate (EDMA) and triethyleneglycol dimethacrylate (TEGDMA), which are widely used in dentistry, with the dipalmitoyl phosphatidylcholine (DPPC) and the DPPC/cholesterol (CS) liposome system was studied by 1H and 13C nuclear magnetic resonance spectroscopy (NMR). EDMA and TEGDMA have a larger interaction with the DPPC liposome system compared to MMA, resulting in changes in chemical shifts. The 13C chemical shift differences of C = C-C-O were larger than those of other carbon portions in methacrylate, indicating that double bonds interact predominantly with DPPC liposomes due to the hydrophobicity of methacrylates. At 37 degrees C, 1H signals from TEGDMA appeared in the DPPC/CS/TEGDMA liposome system, while signals due to H2C = C-C-OCH2CH2 did not appear in the DPPC/TEGDMA liposome system. PMID- 2098206 TI - Influence of water on bonding of various methacrylates to dentin treated with 10% citric acid-3% ferric chloride solution. AB - The bond strength of resins (MMA-TBB resin system), containing 2-hydroxyethyl methacrylate (2-HEMA), 3-methacryloyloxypropionic acid (3MPA), 2-phenylethyl methacrylate (Py1EM) and 2-(1-naphthyl) ethyl methacrylate (NEM), to dentin treated with a solution of 10% citric acid and 3% ferric chloride was measured after being immersed in water at 37 degree C for a long period of time to investigate the influence of water on bonding, and the relationship between the monomer structure and the decrease in bond strength in water. The bond strength of the resins did not change with the time spent immersed in water up to 6 months, but decreased with any further increase in time. The decrease in bond strength of all the resins tested was caused by either the degeneration and swelling of collagen or a difference in the degradation of the resin inside and outside the acid-proof dentin layer. There was no significant relationship between the decrease in bond strength in water and the monomer structure. PMID- 2098207 TI - In vitro adherence of microorganisms to denture base resin with different surface texture. AB - We examined the effects of various denture base resin surface textures on the adherence of microorganisms. S. sanguis and B. gingivalis adhered in greater amounts to the denture base resin than the other microorganisms tested. As to bacterial adherence according to polishing state, S. oralis, B. gingivalis C-101, and B. intermedius C-001 more adhered to the No. 400 paper-polished surface than to the buff-polished and smoothening-treated surfaces. S. sanguis less adhered to the smoothening-treated surface. S. mitis and C. albicans, on the other hand, more adhered to the smoothening-treated surface. For the other microorganisms tested, no relationship was observed between surface texture and bacterial adherence. The fall-off test revealed no remarkable differences in the fall-off of S. sanguis and B. gingivalis C-101 by the types of surface treatment. However, the fall-off of C. albicans was poorest from the No. 400 paper-polished surface. These results indicate that smoothening the denture base surface is important for denture plaque control. PMID- 2098208 TI - New type metal bracket for suppression of resin remaining in debonding. AB - A new type of metal bracket was prepared to minimize the destruction at the bracket-resin interface and to suppress resin from remaining on the tooth surface in debonding. The brackets were made of stainless steel and had a modified cylindrical outward shape (phi 3.8 mm x 1.8 mm), twin-type wings, and a 0.018 inch (0.457 mm) slot. Retentive forces and debonding aspects of residual resin for the brackets were studied using three representative adhesives. The mean tensile strengths at the bracket-resin interface were over 80 kgf/cm2 for all three resins. As the quantitative evaluation for the residual resin condition, a resin remaining ratio (RRR) was adopted. The aspects of the residual resin differed according to the type of adhesive resin used. Almost no resin was detected on the tooth surface just below the central part of the bracket, and even for the peripheral part which did not have an effective resin retention form, the RRR was under 30% for the heavily filled resin. PMID- 2098209 TI - Adsorption of 2-hydroxyethyl methacrylate on dentin from aqueous solution. AB - The adsorption of 2-hydroxyethyl methacrylate (HEMA) on bovine dentin from aqueous solution was examined to clarify the priming effects of HEMA on dentin bonding. HEMA adsorption was characterized by: (1) slow attainment of equilibrium at higher concentrations (after 72 h); (2) a linear isotherm with a maximum possible adsorption, where an abrupt horizontal plateau occurred; (3) the large adsorption of ca. 2.5% by weight at the plateau; and (4) a vertical initial slope of the isotherm. The morphological difference between dentin powder surfaces before and after adsorption could not be determined. After heating, however, dentin powder which adsorbed HEMA was more resistant to demineralization with 6N HCl than the powder which did not adsorb. SEM examinations demonstrated that there was a demineralization-resistant dentin layer in tooth which adsorbed HEMA. The results indicated that HEMA infiltrated into intertubular dentin during adsorption. PMID- 2098210 TI - Temperature dependence of thermal expansion coefficient for palladium-based binary alloy. AB - Temperature dependencies of thermal expansion coefficients for the alloys of Pd Ag, Pd-Cu and Pd-Co binary systems were measured at temperatures up to 900 degrees C, with heating and cooling rates of 5 degrees C/min. The coefficient of thermal expansion of alloys with no transformation in the temperature range of interest in porcelain firing was well approximated by a linear equation of temperature. The constants in the equation were shown as a function of the weight for the added element. Thermal expansion of the palladium-based alloy with no transformation was well estimated at any temperature range and at any composition by using the constants represented here. The coefficients of thermal expansion before and after order-disorder transformation and magnetic transformation were measured in Pd-Cu and Pd-Co alloys, respectively. The results suggest that transient and residual stresses in porcelain-fused-to-metal restorations can be effectively controlled by making use of transformation of the alloy. PMID- 2098212 TI - Clinical application of a static splitting agent for removing the denture from its cast after curing. AB - A very effective method for removing a denture from its cast after curing has been developed using a static expansive agent for hydration. Three filling hole designs for packing the expansive agent into a stone cast were examined to obtain the most effective method of splitting the cast for clinical application. The dynamic strain in the resin denture base was measured during static splitting one filling hole design was the safest for handling and the most effective for removing the denture. The upper tolerance limits for the maximum strain were estimated to be 2.9 x 10(-3) in the upper denture and 3.4 x 10(-3) in the lower denture. These values were lower than one-third of the critical strain corresponding to the proportional limit of the denture resin. PMID- 2098211 TI - Effect of viscoelastic deformation of soft tissue on stresses in the structures under complete denture. AB - The time dependency of stress distribution in the supporting structures under dentures was simulated, under three loading conditions, by visco-elastic finite element stress analysis. In this simulation, viscoelastic material, was used as a model for soft tissue. The results indicate that the viscous flow of soft tissue and the loading position are factors determining stress intensity in the supporting structures under the denture. The stress intensity in the supporting structures was lowered when the occlusal force shifted towards the palatal side. Simulated results support Pound's lingualized occlusion theory. PMID- 2098213 TI - Oxidation effects on porcelain-titanium interface reactions and bond strength. AB - Titanium is strong, resists corrosion and has a low density and excellent biocompatibility. Conventional ceramic-metal restorations have been extensively used in dentistry because of their esthetic appearance and good mechanical properties. This study investigates oxidation effects on the porcelain-titanium interface reactions and bond strength. Pure titanium was treated in a porcelain furnace at temperatures of 600 to 1000 degrees C under either vacuum or air. X ray diffraction analysis of the surface of pure titanium revealed that the relative peak intensity of alpha-Ti decreased and that of TiO2 increased, with increasing firing temperature. The Vickers hardness number of titanium increased with temperature especially over 900 degrees C, and was harder in air than in vacuum. The tension-shear bond strength of the porcelain-titanium system was the highest in the green stage and lowest after 900 degrees C treatment. Metallographic microscopy of the porcelain-titanium interface revealed a thick band-like zone in the sample treated over 900 degrees C. The excess thick layer of TiO2 apparently weakened the bond strength of porcelain-titanium. Unlike the conventional ceramic-gold alloy system the recommended degassing procedure was not suitable for porcelain-pure titanium restoration. PMID- 2098214 TI - Current opinion on conservative methods in hip surgery. PMID- 2098215 TI - Os tibiale externum: etiopathogenesis, cases, clinical aspect and treatment. AB - Based on a consideration of the pathogenesis of os tibiale externum and how it relates to flat foot, the authors discuss the various hypotheses as to how pain is determined. In conclusion, they indicate treatment, and use three cases as examples. PMID- 2098216 TI - The surgical treatment of cervical disc herniation. AB - The authors reviewed 61 cases of cervico-brachialgia due to posterolateral disc herniation treated at the Rizzoli Orthopaedic Institute between 1975 and 1985. Results were positive in 69.3% of the cases, partially negative or negative in 30.7%. An analysis of the results reveals a high correspondence between clinical diagnosis and surgical findings (82%): but the percentage of error in clinical diagnosis (18%) cannot be overlooked. For this reason the clinical diagnosis must be confirmed by CT and/or MRI. In our experience, the posterior approach has proven to be suited to resolving most cervico-brachial pain syndromes due to posterolateral disc herniation. PMID- 2098217 TI - Chondrosarcoma of the hand and foot. AB - Among possible localizations of chondrosarcoma of the limbs, the hand and foot represent the rarest sites. Five-hundred six cases of chondrosarcoma have been observed at the Tumor Center of the Rizzoli Orthopaedic Institute. Of these, 4 were localized in the hand and 10 in the foot. The authors compared their cases with those reported in the international literature. The authors emphasize the particular aspects of the tumor when localized in these sites which may be responsible for late diagnosis and difficulty in differential diagnosis involving synovial chondromatosis and, above all, chondroma, from which chondrosarcoma may originate. PMID- 2098218 TI - Total body bone scan in the evaluation of tumor response to preoperative chemotherapy in the treatment of osteosarcoma. AB - With the introduction of preoperative (neoadjuvant) chemotherapy in the treatment of osteosarcoma, an early preoperative evaluation of the effectiveness of chemotherapy is essential, so that treatment may be modified in cases which are not responsive, and so that the surgical margin may be planned. The authors evaluate the accuracy of total body bone scan with Tc99m MDP in determining response to chemotherapy in 43 patients affected with osteosarcoma of the limbs, and preoperatively submitted to two cycles of chemotherapy with MTX i.v. and CDP i.a. All of the cases were submitted to a double bone scan examination, before and after preoperative chemotherapy. A bone scan evaluation using a qualitative method was compared to the percentage of necrosis observed in the tumorous tissue by histological examination carried out after surgery. In 58% of the cases the two values corresponded perfectly, in 28% of the cases bone scan evaluation overestimated response, and in 14% it underestimated it. In order to obtain quantitative preoperative data on response to chemotherapy in osteosarcoma, orientation towards the use of more sophisticated bone scan methods seems to be necessary, with computerized analysis of captation by dynamic measurement after infusion of Tc99m MDP or by radiocompounds with intracellular fixation such as Ga 67. PMID- 2098219 TI - Fractures in Paget's disease. AB - After analyzing the various types of anatomical and radiographic fractures in pagetic bone, the authors explain the reason for their preference for surgical treatment if the lesion is localized in the lower limbs. This choice allows for a reduction in the duration of immobilization and a lowered incidence of local (rapid and intense osteolysis of the pagetic bone) and general complications (hypercalciuria, at times, hypercalcemia). It is best to resort to internal osteosynthesis for diaphyseal fractures and prosthetic substitution for fractures of the femoral neck where treatment with screws and plates is less reliable due to the fragility of the pagetic bone. Non-surgical treatment may be used for fractures of the upper limb as the duration of the consolidation process, which is always increased, at any rate remains restricted to acceptable limits. Nonetheless, the radiographic occurrence of repair callus is not a sure sign of healing as it may also be affected by the Paget's disease. PMID- 2098220 TI - The surgical treatment of fractures of the pagetic femur: a case report. AB - Based on anatomo-pathological findings in fractures in bones affected with Paget's disease, the authors discuss problems related to treatment. One case is reported in which treatment involved intramedullary osteosynthesis with locked nailing and corrective osteotomy. This type of treatment achieved a dual purpose of obtaining fracture consolidation within a short amount of time, and correcting the deformity. PMID- 2098221 TI - The treatment of idiopathic and secondary hydrarthrosis of the knee by intra articular Rifamycin SV. AB - Fifty-three patients, 28 females and 25 males, aged from 21 to 68 years, affected with mono- and bilateral intermittent hydrarthrosis of the knee and of a non inflammatory nature, were included in an open study. All of the knees involved were treated with intra-articular infiltrations with Rifamycin SV. The weekly dosage of Rifamycin SV was 500 mg; the average duration of treatment was 6 weeks. Follow-up 1 year after the end of treatment showed a decrease or regression in joint effusion in all of the knees treated. PMID- 2098222 TI - The study and development of a connection device (D.R. IOR) in halo-plaster and halo-jacket immobilization and traction systems. AB - Most of the halo connection devices currently used with both the halo-plaster and halo-vest cannot be adjusted on the different displacement planes during reduction treatment. This makes it difficult to obtain good radiograms for the interposition of connection bars. The connection device designed by the Rizzoli Orthopaedic Institute (D.R. IOR) allows for movements in rotation and translation, preventing loosening of the system. Moreover, radiographic monitoring may be obtained in the best conditions possible, by moving the connection rods backwards or forwards without changing the spinal axis. PMID- 2098223 TI - The epidemiology of idiopathic scoliosis in the city of Bologna. A three-year review of positive cases. AB - The authors report the results obtained in a review of all of the young patients who have been found to be affected with vertebral deformity in an epidemiological study conducted during the academic years 1983-84 and 1984-85. There is predilection for the female sex, which is also more vulnerable to the risk of progression. Menarchal age constitutes the most important period for the progression of the deformity. The most frequent type of curve observed is the double primary one, in particular, right thoracic and left lumbar, which proved to be that most vulnerable to angular progression. The cases which in a previous screening had been defined risk cases were followed-up, and thanks to early diagnosis and suitable treatment surgery was not required in any of these. PMID- 2098224 TI - Quiz. Aneurysmal bone cyst. PMID- 2098225 TI - [Factors influencing prognosis of tongue cancer: a retrospective study of 260 cases]. AB - This paper is a retrospective study of prognostic factors involved the tongue cancers. The 3 and 5 year survival rates of the tongue cancer were 63.77% 61.2%, respectively. I. The prognosis in females was poorer than that of males II. The prognosis of oral tongue cancer was better than oropharyngeal tongue cancer. III. The larger the cancer, the poorer the prognosis. IV. Node involvement was an important factor influencing survival rate. V. Immediate repair of defect did not influence survival rate. VI. The main cause of death was recurrence of the primary site, which generally occurred within 3 years postoperatively. The authors suggest that I. The depth of the tumours infiltration should be an index for the evaluation of prognosis. II. The neck dissection, either functional or radical, should be carried out as a routine. III. The management of mandible will be determined according to the tumor infiltration. IV. immediate reconstruction is recommended. PMID- 2098226 TI - [Anatomy and microstructure of the disco-malleolar ligament]. AB - The disco-malleolar ligament was studied with the method of the anatomy and histology, and it's function was observed in the living people. It was found that the ligament takes its origin from the neck and anterior process of the malleus in middle ear and inserts into the capsule and meniscus of the temporomandibular joint. Part of the fibers was mixed with the spheno-mandibular ligament and attaches on the lingula of the mandible. The disco-malleolar ligament consists of collagenous fibers and elastic fibers. A peri-ligamentous space exists between the ligament and bone tissue. It was found the tympani membrana light cone area became smaller in opening position and larger in closing position. The existing peri-ligamentous space of the disco-malleolar ligament is a latent way between temporomandibular joint rear and tympanum. PMID- 2098227 TI - [Effect of investment on adaptation of the PFM coping]. AB - The purpose of this study is to investigate the influence of two investing methods, one time investment and two-time investment, to the adaptability of the PFM coping, using CW-PA base alloy and its phosphate investment. The result shows that the expansion of the investment is influenced by the investing methods (P less than 0.05). One-time investment has a larger expansion than two-time one for the cause of that it is without limit of the gypsum investment. It can compensate the Ni-Cr-Nb base alloy's contraction more fully, therefore a better fit of the PFM coping can be got. PMID- 2098228 TI - [Isolation and identification of oral spirochaetes and Fusobacterium in juvenile periodontitis]. AB - Periodontal pocket specimens of 40 juveniles periodontitis (JP) and specimens from gingival sulcus in 40 normal juveniles (NP) were examined. 25 strains of anaerobic oral spirochaete (62.5%) (17 strains were Treponema microdentium, 3 strains macrodentium, 2 strains T orale, 3 strains Borrelia) and 21 strains of fusobacterium were isolated in 40 JP. In 40 NP, 2 strains of spirochaetes (5%) and 3 strains fusobacterium (7.5%) were found. This study shows that there is a relationship between the infection of spirochaeta, fusobacterium and JP. PMID- 2098229 TI - [Experimental and clinical evaluation of the temporomandibular joint arthroscopy]. AB - To evaluate the clinical value of the TMJ arthroscopy, 10 monkeys and 48 patients were examined. No special injuries and serious complications were revealed. The field of vision of arthroscopy is wide enough to observe the upper compartment, but there is some difficulty in inspecting the lower one. Meanwhile, different kinds of pathological changes were observed on the disc, fossa, eminence and synovial membrane through the arthroscopy in the patients with TMJ disorder. Thus it can be concluded that the TMJ arthroscopy is very important and useful to inspect the joint cavity and to diagnose the TMJ diseases. PMID- 2098230 TI - [Angiographic study of osteosarcoma and fibrosarcoma of the jaw]. AB - It has been well known that the sarcomas of jaw are very vascularized, but reports on the angiography of jaw sarcomas were very few. Based on the preoperative angiography of 3 cases of jaw bone sarcomas and arteriography of their specimens, it has been noticed that the supplying arteries of the mandible ramus sarcoma can be directly from the external carotid arteries; and the supplying arteries can be from inferior alveolar artery in sarcomas of the body of mandible. The tumors are more vascularized than the surrounding normal tissues, and the direction of the arteries can be from central to peripheral in the tumors, which are different from the long bone sarcomas. The vascularization and the retarded blood flow in the tumor are the significant anatomic bases for local perfusion chemotherapy of jaw sarcomas. PMID- 2098231 TI - [Activity of bone resorption for interleukin-1, epithelium thymocyte-activating factor and fibroblast thymocyte-activating factor]. PMID- 2098232 TI - [Effect of phenolic resin fluid on the dentin resistance]. AB - SEM observation was made in the experiment to analyze the ultrastructure of resinified dentin. Phenolic resin fluid permeates in to the dentinal-tubule and set in it. The permeability of this agent was also able to permeate into intercellular substance and changed the appearance of inter-weaved fibril to the condition of agent had set. According to the Fracture Mechanics, it was not beneficial to resist the fracture progress if the microspace had been fulfilled by the agent. The tensile stress of resinified dentin was 387 kg/cm2, which was 30 kg/cm2 lower than that of unresinified-dentin. PMID- 2098233 TI - [TMJ reconstruction of the intracapsular condylar vertical fracture]. AB - According to literature, it is difficult to make an early correct diagnosis and treatment of the intracapsular condylar vertical fracture. The author recently suggested a new method to diagnose and treat this kind of fracture with an optimal result. The diagnostic and treatment procedures are: 1. To take a condylo pterygo-maxillo-oblique tomography which can clearly demonstrate the position of the bone fragment. 2. To remove the bone fragment by submandibular incision with an oblique osteotomy of the posterior part of the ramus. Therefore the secondary injury to the disk and the superior cavity could be avoided that is essential for TMJ reconstruction. 3. To reconstruct the TMJ after condyloplasty under the centric relation. Eight cases were successfully treated by this method. In this paper the details of the operation are described and discussed. PMID- 2098234 TI - [Effects of acidic phosphate fluoride on the protein compositions of acquired pellicle in vitro]. AB - The human enamel powders treated with acidic phosphate fluoride (APF) were used to react with human mixed saliva and purified proteins. Before and after treated with APF, the changes of fluoride content in the enamel and the salivary proteins adsorbed on the enamel surfaces were noticed. The results are as follows: 1. The post-treated enamel fluoride is increased, and the production is fluorapatite besides a little CaF2. 2. No effect of APF on the kind of salivary proteins adsorbed on the enamel is found. 3. The quantity of salivary proteins adsorbed on the enamel is increased in different percentage and the proportion of the proteins on the enamel surface may be changed. Therefore, we believe that these changes must be one of the APF's mechanisms on caries prevention. PMID- 2098235 TI - [Gross anatomy and microstructure of the orbicularis muscle and philtral contour]. AB - In order to improve the reconstruction of orbicularis oris muscle and philtral contour and the effect of repair in the cleft lip, orbicularis oris muscle was dissected on three adult cadavers and two newborns with normal lip. Histological studies of seven newborn cadavers were made with sections in transverse, sagittal and coronal planes and stained with masson's trichrome technique. The results are as follows. The orbicularis oris muscle consists of two layers: deep and superficial. The muscular fibers of deep layer originate from the buccinator, its upper and lower fibers horizontally and respectively enter the upper lip and lower lip, while the middle fibers are decussated on the corner of the mouth. The marginal part of the orbicularis oris muscle curls upon itself forming vermilion. The superficial layer originates from the muscles of facial expression, consists of an upper and lower bundle. The lower bundle derives its fibers from depressor anguli muscle and inserts in the skin of the philtral ridges. The upper bundle attaches to the anterior nasal spine. The levator labii superioris mingles with the rim of orbicularis oris, insert into the vermilion border, forming labial arch and peak. There are longitudinally running fibers in the philtral ridges. In the sagittal section of the philtral groove, it was seen that a few of vertical muscle running from the part marginalis of the orbicularis oris and inserting into the lower skin of philtral groove. In the horizontal section of upper lip, muscular bundles from the lateral incisor bone inserting into ipsilateral and contralateral philtral ridges were seen. PMID- 2098236 TI - [Clinicopathologic and immunohistochemical study of epithelial-myoepithelial carcinoma]. PMID- 2098238 TI - [Pathological study of oral submucous fibrosis]. PMID- 2098237 TI - [Review and discussion of ligating or resecting the common and internal carotid artery]. PMID- 2098239 TI - [Relation between the lesion of molar furcation and projection of cervical enamel]. PMID- 2098240 TI - [Experimental study of the relation between changes in and patency rate of irradiated vessels after microvascular anastomosis]. PMID- 2098241 TI - [Clinical analysis of 13 cases of psychiatric disorder associated with Klinefelter syndrome]. AB - 13 cases of psychiatric disorder associated with klineferter are comprehensively analysed in respect to the manifestation of body, the characterization of nature, the intellective growth, the psychotic symptoms, and the find of EEG, dermatoglyphic, and cytogenetic etc. in this paper. The authors discussed with respect to the intellective level, the causes of psychiatric disturbances, and the treatment, indicated if we pay not attention for a careful examination in clinic that lead to easily misdiagnosis, and advanced a view of classtype of psychiatric disorder and the main of differential diagnosis. PMID- 2098242 TI - [23 hair trace elements measurement in patients with schizophrenia]. AB - 23 hair trace elements were determined with the method of Inductively Coupled plasma Quantometer (ICP-AEP) in 85 cases of schizophrenics and 65 cases of normal controls. The results indicated that: there were no significant differences between age and the samples of the two groups; Significant sex differences were observed in schizophrenics, 11 trace elements were higher in female (P less than 0.01), 5 trace elements were increased in male (P less than 0.01); As a whole, 17 trace elements were decreased in schizophrenics than normal controls, the differences were significant (P less than 0.01). PMID- 2098243 TI - [A contrast between the MMPI with the System Check List 90]. AB - This study tested 131 patients with psychoses and contrasted the MMPI with the SCL-90. It was found that the nine groups of elemental symptoms in the SCL-90 was highly related with the corresponding symptoms in the MMPI. However, the relatively of groups in the two scales is different in the three diseases of schizophrenia, depression and neurosis. It was expressed that the three mental diseases possessed different psychopathologic characters. The result corresponded to clinical experience and also showed that SCL-90 was a self-rating scale with higher validity and spread of the scale was feasible. PMID- 2098244 TI - [Observation on ultrastructure of microvasculars in experimental cerebral ischemia]. AB - Ultrastructure changes in microvasculatures were observed in cortical areas of cerebral post-ischemia. Mitochondria distention and endothelial swelling are first damage form in microvasculatures. A large number of pinosomes, damage of continuity of endothelial and basement membrane, membrane-bound intra-luminal bodies, narrow of lumen, compression of perivessels edema were considered as injury basis of microcirculation disturbance and edema in cerebral post-ischemia. PMID- 2098245 TI - [Intracerebral hemorrhage related with cerebral amyloid angiopathy]. AB - The clinical and neuropathologic findings in 11 cases with intracerebral hemorrhages related to CAA were reported. Their age ranged from 45 to 79 years, the average being 61.8 years. The hematomas were all in cerebral lobes, except two patients whose hematomas were in the basal ganglia and thalamus. These hematomas were in irregular shapes, ruptured into ventricles and/or subarachnoid space in all cases. The vessel's wall of arteries in the leptomeninges, superficial cortex and those adjacent to hemorrhagic foci showed considerable thickness. Hemorrhagic foci showed considerable thickness. Homogeneously eosinophilic structures deposited in these vessel's wall of several small arteries. Some of these vessels showed luminal stenosis. Congo red staining confirmed characteristic amyloid apple-green birefringence under polarizing microscope. PMID- 2098246 TI - [Relationship among blood pressure, viscosity of blood and cerebro-vascular disease]. AB - In this article, 163 cases of hypertension patients and 117 cases of stroke patients with acute period including 43 cases of hemorrhagic strokes and 74 cases of ischemic strokes were analyzed between average arterial blood pressure and blood viscosity. The curves of relation of blood pressure versus blood viscosity in the hypertension patients' group showed "M" shape. The hemorrhagic stroke patients were located by up-side of the "M" shape curve and the ischemic stroke patients were situated by the down-side of the "M" shape curve. PMID- 2098248 TI - [Cerebral germinoma]. AB - 16 cases of cerebral germinoma are reported. This tumor is comparatively rare. Since it is usually located in pineal and easily be confused with pineloma or ectopic pinealoma, its terminology, source of the tumor tissue, histopathological characteristics, diagnosis and differential diagnosis are discussed by the authors. According to the high mortality of the operative treatment, the radiotherapy is suggested. PMID- 2098249 TI - [Adrenomyeloneuropathy in 4 brothers]. AB - Four brothers with adrenomyeloneuropathy are reported. They have developed darkening of the skin the sign of adrenal insufficiency at age of 5-10. During 10 years after that time progressive spastic paraparesis has appeared gradually in all of them and has had aggrevative tendency abruptly in late. Three male cousins of the proband probably died of "juvenile type" of adrenoleucodystrophy. PMID- 2098247 TI - [Adult metachromatic leukodystrophy]. AB - An adult case of metachromatic leukodystrophy confirmed by characteristic findings of the brain and superficial sural nerve biopsies, but with absence of deficiency of arylsulfatase A activity in the leucocytes, was reported. Ultrastructurally, typical membrane-bound inclusions were found in white matter and Schwann cells. The long course of thirty years and late onset of illness were discussed. PMID- 2098250 TI - [Video/EEG, the epileptic monitoring system]. AB - Seventy-six seizures in thirty-four patients with epilepsy and suspicious of epilepsy were monitored by Video/EEG which was designed and made by the authors and identified by the scientific experts considered to be standard. The average time of each patient monitored was 6.7 hours. The positive record of fifty-six seizures were analyzed: The seizures of twenty-four patients (70.5%) were diagnosed as epileptic in nature; two patients (5.8%), the seizures were due to organic brain diseases and in eight patients (23.5%), they were pseudoseizures. The diagnostic rate for epileptic type was 87.5%. The clinical use of Video/EEG shows that functions of this apparatus has attained the international level as compared with the identical one made in foreign country. It is high qualified with multifunctions and low in price. It can also apply in fields of psychology. Psychiatry, biology and in studying of sleep, respiration etc. Therefore, the Video/EEG which we made is a apparatus suitable for our national condition. PMID- 2098251 TI - [Image processing of topographic EEG in epilepsy]. AB - The processing of epileptic computerized topographical EEG (CTE) with the principle of image enhancement and point-by-point process was reported. The results indicated that the high potential distribution of CTE markedly reduced, the focus location was prominent and the mirror nearly disappeared after processing CTE image. The difference increased between the spike grey and the fast wave. This is advantageous to the surgical treatment of epileptic focus in brain. PMID- 2098252 TI - [Non-operation management of 12 cases with brain abscess demonstrated by CT scan]. AB - This paper reported 12 cases with brain abscess demonstrated by CT scan. Using antibiotic management without surgical intervention, in 10 cases the curative effects were satisfactory. The paper indicated that CT scan was very useful in prompt and correct diagnosis of brain abscess and with sequential CT scan medical therapy was feasible. It is significant in treatment of brain abscess especially for the patients who have a poor general condition, have the brain abscess located in important functional area or have multiple abscesses so that the operation is difficult for them. PMID- 2098253 TI - [CT scans in the diagnosis of cerebellar hemangioblastomas. Analysis of 21 cases]. AB - Computed tomography (CT) scans in 21 patients with pathological verified cerebellar hemangioblastoma were analysed. There were 14 cases of cystic nodular pattern, 4 cases of nodular pattern and 3 cases with the pattern of cyst only in this series. The characteristic features of hemangioblastomas on the CT scans usually consisted of large circumscribed cystic low density lesions with a small enhanced nodule in each of them. On surgical operations 20 cases in this series were classified to be of cystic-nodular pattern. In order to show the cystic nodular pattern in a better manner on the CT the thin slice CT scan 5 should be recommended in addition to the use of an appropriately increases amount of intravenous contrast medium when hemangioblastoma of the cerebellum would be suspected. PMID- 2098254 TI - [Effect of stress on spontaneously hypertension rats and mechanism of its action]. AB - Social-psychological stress was closely related to psychosomatic diseases. Why could it cause the psychosomatic diseases and worsen some other diseases? No satisfied answer got yet. The blood pressure of SHR before and after laboratory stress were compared in this article and preliminarily studied the mechanisms of its action. It was found that stress state could expedite the onset of hypertension in SHR and worsened it continuously. After stress, the NE, E, and TC/HDL-C, TG all increased obviously. It indicated that social-psychological stress was closely related to essential hypertension. PMID- 2098255 TI - [Lysosomes in embryonic cell differentiation]. AB - Lysosomes as a modeling factor of embryonal morphogenesis occupy an important place in the systemic structural and ultrastructural studies on prenatal development of man. Human embryos at the age of 6 to 10 weeks of embryonal development, obtained after interruption of normal pregnancy by the method vacuum excochleation according to Andreev. Lysosomes were investigated in cells of groups, chosen in advance, from organs with various origin and degree of cellular differentiation: neurones of the spinal cord and spinal ganglia, keratinocytes of the epidermis, epithelium of lentil vesicle, chondrocytes of Merkel's cartilage, epithelium of intestines and bronchi, hepatocytes, myoblasts, corticocytes, of coelomic fetal and definitive cortex of the adrenal, metanephros, coelomic epithelium of gonad, epithelium of Mueller's duct and Wolff's ducts, hemopoietic foci and capillary vasothelium. Lysosomes were divided into three groups: primary lysosomes, secondary autolysosomes and cytosomes. Lysosomes participate in the following processes during the course of embryonal organogenesis: 1. destruction of cells of transient embryonal organs; 2. destruction and demolition of whole cells during the course of normal embryonal development; covering with a membrane and lysis of inferior cellular organelles; 5. lysis with consecutive assimilation of cytoplasmic inclusion; lysis of secretory products. PMID- 2098256 TI - [The effect of insulin on thrombocytopoiesis and thrombocytopoietin biosynthesis in rats]. AB - The influence of insulin on the number of thrombocytes of male and female rats as well as on the percentage of 75Selenomethionine (75Se-M) incorporated, on bone marrow megakaryocytes and thrombocytopoietic activity of the plasma was studied under normal conditions. It was established that a 3-day administration of insulin induced in both go groups of rats an increase in thrombocyte number, in the percentage of incorporated 75Se-M, in bone marrow megakaryocytes as well as in their total number and in all stages from I to IV with shift to mature cellular forms (III and IV stages). The thrombocytopoietic activity of the plasma was raised as well. In conclusion it could be said that insulin stimulates strongly thrombocytopoiesis in rats as it raises considerably the biosynthesis of its specific humoral regulator thrombocytopoietin. This effect of insulin does not demonstrate sex dependence. PMID- 2098257 TI - [The effects of isotheoline (IST) on the nonvascular smooth musculature]. AB - The influence of IZT on nonvascular smooth musculature in experiments in vitro was studied: on isolated intestine of the rabbit, ileum of the guinea pig, an uterine horn of the rat and guinea pig, vas deferens of the rat; as well as in vivo: on an experimental model of bronchospasm of guinea pigs, induced by acetylcholine, histamine and serotonin. Isometric contractions were recorded, and in the experiments in vivo--the tonus of the bronchial smooth musculature by a piston recorder. The obtained results showed that in experiments in vitro IZT increased the dose dependent tonus of intestinal smooth musculature; inhibited predominantly at low concentrations like clonidine the contractions of vas deferens of the rat by low frequent field stimulation--0.1 Hz and its influence was weak in respect to contractions of this organ, induced by high frequent field stimulation (10 Hz); inhibited the contractions of vas deferens in response to exogenously administered NA. IZT inhibited only bronchoconstrictor effect of serotonin in experiments in vivo. It was established that the effects of IZT both in respect to the vascular and to the nonvascular smooth musculature were Ca++ dependent and were connected with pre- and postsynaptic alpha-adrenergic receptors. PMID- 2098258 TI - [A compartment analysis of the significance of extracellular fluid volume for body fluid dynamics]. AB - The curve of a reduction in plasma concentration of the indicator substance creatinine for a period of 120 to 240 min was investigated after single intravenous administration of creatinine in a dose of 150 mg/kg on dogs. A model for two compartment distribution of the indicator substance was used as the first compartment was intravasal, but the second--interstitial space of body fluids. The following parameters were estimated: renal clearance, volume of distribution, glomerular filtration, intercompartment clearance and velocity constants of transport between the two compartments. An increase of the volume of extracellular fluid (ECF) was induced by intravenous infusion of 2% of sodium chloride solution in the amount of 30 ml/kg. A reduction in the volume of ECF was caused by peritoneal dialysis with isotonic solution of glucose in the amount of 5% of the body mass. After an increase of the volume of ECF there was an increase in the volume of distribution, elevation of glomerular filtration and a reduction in the velocity constant of transport from the intravasal to interstitial fluid. There was a reduction in the volume of distribution, limitation of glomerular filtration and increment of velocity constant of the transport. The established changes in the velocity constants of the transport showed changes in the dynamics of body fluids, which could be due to vasoconstriction or vasodilation as a mechanism of myogenic autoregulation during changes in the volume of ECF. PMID- 2098259 TI - [The effect of the newly synthesized barbiturate HB-7, phenobarbital and pentobarbital on the GABA content of the brain in rats]. AB - The content of GABA in the following regions of the brain: cerebellum, left and right hemisphere was studied on white male rats. The determination was made by the method of Sutton and Simmonds (1974). One control and 7 experimental groups were investigated. All examined substances were administered intraperitoneally and the animals were decapitated at their peak activity. The effect of newly synthesized hydroxyl amine barbiturate HB-7, administered in several doses, was studied, comparing it with the action of pentobarbital (PB) and of phenobarbital (PB). A considerable increase in the content of barbiturates was established in the cerebellum of rats under the influence of the applied barbiturates while the content of GABA in both large hemispheres was less affected by the administered compounds. A conclusion is made that a single administration of barbiturates affects the content of GABA in some cerebral structures of the rat. PMID- 2098260 TI - [A histological study of the experimentally damaged ligamentous apparatus of the joints in rabbits treated with celeston]. AB - A histological study was made on experimentally damaged ligament apparatus of the ankle joint of rabbits, treated with celestone, divided into three groups: celestone was administered immediately after the damage in the first group. Morphological changes were manifested slightly. Celestone was administered on the 20th day after the damage in the second group. A manifested chronic productive inflammatory process with hyalinization was established morphologically. The most manifested changes were found in the control group of rabbits, which were not treated with celestone. Intraarticular, administration of celestone in ligament damages immediately after trauma prevents occurrence of severe fibrous changes and contributes for functional recovery of the ligament apparatus. PMID- 2098261 TI - [Experimental research on the toxicity of pharmapentoxifylline (I)]. AB - Results from the study on acute, subacute and chronic toxicity of the therapeutic preparation pharmapentoxiphyline (PP), produced by Pharmachem, are described. The experiments were carried out on 312 male and female white rats. According to the limiting index of LD50 with, Oral dose of (1220 mg/kg of body mass for male rats and 1050 mg/kg for female rats) and intraperitoneal PP dose of PP (230 mg/kg for female rats and 235 mg/kg for female rats) it was included into IV class of slightly toxic compounds. Doses of 100, 300 and 600 mg/kg/oral administration) and 30, 75 and 150 mg/kg (intraperitoneal administration) were used in subacute and chronic experiments. Integral, hematological and biochemical methods and parameters were applied for evaluation of the toxic effect. There was no hemato-, hepato- and nephrotoxicity after oral and intraperitoneal administration of PP in doses of 10 and 30 mg/kg for a period of 3 months. Some recommendations, which should be taken into consideration during continuous treatment with PP, are given on the basis of a complex evaluation of the results from the hematological parameters. PMID- 2098262 TI - [Experimental research on the toxicity of pharmapentoxifylline (II)]. AB - The results from morphological studies on liver, lung, heart, spleen, intestine, brain, skin, testes (ovaries), obtained in the end of the first and third month of animals, treated with pharmapentoxiphyline (PP), are described. The experiments were carried out on 312 white rats (male and female), divided into 2 series: I series--oral usage of the preparation in doses of 100, 300 and 6 mg/kg, II series--intraperitoneal administration in doses of 30, 75 and 150 mg/kg. It was established that PP, administered for a period of 3 months orally in a dose of 100 mg/kg and intraperitoneally in a dose of 30 mg/kg did not induced changes in the structure of all examined organs. Slight dystrophic changes in liver, lung and spleen occurred in the end of the third month under the influence of an oral dose of 300 mg/kg and an intraperitoneal dose of 75 mg/kg. The obtained results are discussed in connection with the pharmacological action of drug-peripheral vasodilatator. PMID- 2098263 TI - [Anti-islet antibodies: methods for their determination and etiopathogenetic importance]. PMID- 2098264 TI - [The functional interactions between 2 electron-transport links in liver endoplasmic membranes]. PMID- 2098265 TI - [The ultrastructure of the inferior olivary complex in ground squirrels (Citellus citellus L.). The neuropil. Age-related changes in the axons]. AB - The morphological characteristics of axon terminals among a neuropil in the lower olivary complex of ground squirrels at various ages were studied by an electron microscope. The presynaptic part of the chemical synapses in the glomerular or outside glomerular position among the neuropil pf this nuclear complex were axon terminals and terminals "en passant". These axon elements participate in the formation of crash-like synapses with somatic, dendrite prickles, but also with dendrite adjuncts in the formation of complex synaptic connections. A considerable part of myelin axons and axon terminal were changed in old ground squirrels during all seasons. There were two varieties: 1. axon elements with preserved sizes and dense bodies, myelin-like figures, a large number of mitochondria and glycogen granules were found among normal organoids. 2. myelin and amyelin "spheroids" with various sizes and inner structure. The changes axon elements of the neuropil in the inferior olivary complex of ground squirrels at various ages during all seasons are physiological probably connected with the process of aging. PMID- 2098266 TI - Functional, biochemical, and histopathological evidence of airway obstruction in rats following a four-hour acute inhalation exposure to n-butyl isocyanate. AB - Pulmonary function, arterial blood gases, acid-base status, and bronchoalveolar lavage fluid (BALF) composition were assessed in male Wistar rats after a single 4-h exposure to 0, 7.6, 23.5 or 55.2 mg n-butyl isocyanate (n-BIC)/m3 air. No significant changes other than transient clinical signs were observed in the rats exposed to 7.6 mg/m3 air. Four weeks after exposure the animals of the 55.2 mg/m3 group showed significant effects: those were pronounced histopathological changes of airways and parenchyma, and elevated relative lung weight. The neutrophils, LDH, and protein in BALF were elevated. Quasi-static lung compliance, peak expiratory flow rate, mean mid expiratory flow rate were decreased whereas lung resistance, residual volume, and single breath CO-diffusing capacity were increased. Blood gas measurements revealed an elevation in hemoglobin, pH, arterio-alveolar oxygen difference, and venous admixture. Arterial pO2 and pCO2 were decreased. In animals exposed to 23.5 mg/m3 only marginal effects were detectable. PMID- 2098267 TI - Characteristic of spontaneous intraperitoneal cysts in golden hamsters and European hamsters. AB - Epidemiological study of 340 Golden hamsters and 200 European hamsters bred as laboratory animals and necropsied between 1985 and 1989 in our facility (affiliation 2) revealed high incidence of spontaneous cysts. The incidence was in general higher in European (26 to 62%) than Golden hamsters (0 to 15%). The cysts, of different sizes, were localized first of all in the liver, and secondly (in European hamsters only), in the caecum wall. Light microscopic and electron microscopic examinations showed that the cysts are lined by flattened to cuboidal epithelial cells which, on their surface, have microvilli of different lengths and underneath a continuous basement membrane. These examinations lead further to the interpretation of the liver cysts as cystic distensions of the bile ducts. The cysts in the caecum wall could be interpreted as dilatations of the lymphatic vessels. As to the etiology, which remains unclear, several hypotheses are discussed. PMID- 2098268 TI - Quantitative cytomorphology of megakaryocytes in chronic myeloproliferative disorders--analysis of planimetric and numeric characteristics by means of a knowledge based system. AB - Numeric and planimetric parameters of megakaryocytes have been analyzed in 162 bone marrow biopsies of patients with chronic myeloproliferative disorders--CMPD- and controls by means of an inductive knowledge-based system in combination with a multivariate data analysis. To achieve a reliable differential diagnosis between the different entities of CMPD and controls, decision trees and the rank order of the best discriminating parameters have been calculated. The cases measured were defined by 3 histopathologists who were involved in the elaboration of the Hannover Classification of CMPD. The results demonstrate striking numeric and morphologic characteristics of the megakaryopoiesis in each separate primary category of CMPD, that is (1) chronic myeloid leukemia of the common type and (2) with megakaryocytic increase, (3) polycythemia vera, (4) primary or idiopathic thrombocythemia, and (5) chronic megakaryocytic-granulocytic myelosis. Thus, the morphometric measurements did confirm the validity of the Hannover Classification of CMPDs. In order to evaluate the information contained in large quantitative and semiquantitative data bases and diagnostic decisions, knowledge-based expert systems seem to represent a valuable addition to conventional statistics. PMID- 2098269 TI - Oral cancer in northern Thailand. AB - Statistical material accumulated at the Faculty of Medicine, Chiang Mai University, Thailand, revealed that oral cancer ranked third in both sexes during 1975-1984 and 1981 alone. In 1987 oral cancer had dropped to rank 7 of cancers of all sites. Since there is evidence of disappearance of traditional chewing and smoking habits in Northern Thailand this may result in changing incidence of oral cancer in this province. PMID- 2098270 TI - Carcinogenesis induced by black pepper (Piper nigrum) and modulated by vitamin A. AB - Painting and feeding of mice with 2mg of an extract from black pepper on 3 days a week for 3 months results in a significant increase of the number of tumor bearing mice. Tumor incidence is reduced in those groups of experimental animals receiving 5 or 10mg Vitamin A-palmitate twice weekly for 3 months by feeding or painting during and subsequent to application of pepper extract. Feeding of mice with powder of black pepper in diet (50g/3kg food) has no impact on carcinogenesis. PMID- 2098271 TI - Contribution of immunohistochemistry toward the diagnosis of tumors of laboratory rats. AB - A polyclonal antibody detecting S-100 protein (S-100) and a monoclonal antibody demonstrating epithelial cell (Lu-5) were used in addition to routine, hematoxylin-eosin stain to improve the identification of tumors of neural or epithelial origin diagnosed in conventionally treated tissue from rat bioassays. Among 108 lesions tested for S-100, 51 reacted positively; they included benign and malignant schwannoma, endomyocardial disease, some cases of benign and malignant thymoma, and renal tubular adenoma. S-100 protein is considered particularly useful for discriminating of neoplasms of Schwann cell origin from mesenchymal tumors. 31 of 51 lesions tested for Lu-5 reacted positively: they comprised adenoma, carcinoma, benign and malignant thymoma and atriocaval node tumor of the heart. Lu-5 was especially useful to distinguish epithelial from mesenchymal neoplasms and was capable of identifying epithelial elements in lymphocyte-rich thymomas as well as in dedifferentiated or autolytic tumors. The binding of both antibodies in neoplastic tissue was compared with a complete set of anatomically normal rat tissues. PMID- 2098272 TI - The contribution of experimental studies to risk assessment of carcinogenic agents in humans. PMID- 2098273 TI - Histological types of laryngotracheal tumors induced in Syrian golden hamsters by nitrosomorpholine and nitrosopiperidine. AB - The chronic oral administration of nitrosomorpholine (NM) and nitrosopiperidine (NP) to 360 adult Syrian golden hamsters of both sexes resulted in the induction of a high incidence of laryngo-tracheal tumors, which in the group treated with 0.01% solution of NM affected up to 80% of the males. A total of 232 different laryngo-tracheal tumors were found. 36 of these were located within the supraglottic and glottic larynx, 62 were within the subglottic and glottic larynx, and 134 arose within the trachea. Among the laryngeal supraglottic and glottic tumors there were 18 squamous cell carcinomas, 16 squamous cell papillomas and only 2 mixed cell mucoepidermoid papillomas. All the subglottic laryngeal tumors and tracheal tumors were mixed cell mucoepidermoid papillomas. In this study, the squamous cell carcinomas observed within the larynx of hamsters bear morphological and biological similarities to their tumor counterpart found in the larynx of adult man. The laryngeal squamous papillomas observed in this experiment are not similar to the squamous papillomas occurring in man during infancy and childhood. The mixed cell mucoepidermoid papillomas of the hamster trachea and subglottis are a peculiar neoplasm of this species, which morphologically and biologically differs from the cases of tracheal papillomatosis described in man, as well as from the mucoepidermoid tumors of major and minor salivary gland origin also seen in this latter species. PMID- 2098274 TI - Growth factors in progression of human esophageal and gastric carcinomas. AB - Human esophageal and gastric carcinomas express multi-autocrine growth factors and hormones including epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and beta, platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and sex hormones. Overexpression of EGF, TGF-alpha and EGF receptor (EGFR) by tumor cells is closely correlated with the tumor invasion and patient prognosis. This is substantiated by the facts that EGF and TGF-alpha act as autocrine growth factors and then induce the expression of mRNAs for multi-growth factors and their receptors (EGF, TGF-alpha, EGFR, ERBB2, PDGF). Moreover, they stimulate the expression of metalloproteinase genes suggesting that EGF and TGF alpha successively evoke cascade phenomena which are most convenient for tumor progression, invasion and metastasis. On the other hand, multiple oncogene alterations take place in the process of tumor progression. HST-1 and INT-2 genes which is a member of fibroblast growth factor gene family, are amplified in approximately 50% of primary tumors and all the metastatic tumors of esophageal carcinomas. The amplification of ERBB2 gene in metastatic gastric carcinomas is detected more frequently than in primary carcinomas. Overexpression of multi growth factor-receptor systems might lead to genetical alterations. Scirrhous gastric carcinoma has vast fibrous stroma with rapid and extensive growth and exhibits high malignancy. Its fibrous stroma may account for synchronous overexpression of EGF, TGF-alpha, PDGF, IGF and TGF-beta by tumor cells. Most of well differentiated adenocarcinomas show overexpression of p 185ERBB2 and coexpression of p 185ERBB2, and EGFR evidently correlates with high malignancy. In conclusion, the accumulation and interaction of several growth factors produced by tumor cells are necessary for the progression of human esophageal and gastric carcinomas. They may be attributed to genetic changes including activation of oncogenes, inactivation and deletion of anti-oncogenes and transcriptional regulatory sequences. PMID- 2098276 TI - Absenteeism--where do you draw the line? PMID- 2098275 TI - Applications of immunohistochemistry in rodent tumor pathology. AB - Immunohistochemistry can serve as a valuable adjunct to rodent tumor pathology. Specific antigens may be localized to cells and tissues in normal organs, preneoplastic lesions, and benign and malignant tumors. The immunoreactivity of polyclonal and monoclonal antibodies to these antigens provide a more accurate basis for tumor diagnosis and aid in understanding pathogenesis. Ultimately, the application of more precise understanding of tumor histogenesis and diagnosis will lead to more accurate interpretations of tumor incidence data for safety assessment in toxicology. PMID- 2098277 TI - Manpower requirements for dental technicians. PMID- 2098278 TI - Casting techniques in lost wax. PMID- 2098279 TI - Ceramics and pottery. PMID- 2098281 TI - [Eduard Gitsch on his 70th birthday]. PMID- 2098282 TI - [Radical surgery in gynecologic cancers]. AB - The issue of surgical radicality in patients with gynecologic cancers is not seen as clearly elsewhere as it is in Austria. Systematic extirpation of the affected organ and the complete attendant lymphatic tissue can lead to excellent results. In patients with stage IIb cervical cancer, especially those with positive para aortic nodes, surgery produces better survival rates than radiotherapy. In ovarian cancer, systemic lymphadenectomy has led to a sudden increase in survival and cure rates. PMID- 2098280 TI - Basement membrane components secreted by mouse yolk sac carcinoma cell lines. AB - Three new cell lines (NE, ME, LRD) were cloned from mouse-embryo-derived teratocarcinomas and characterized on the basis of developmental, ultrastructural, and cytochemical criteria as nullipotent embryonal carcinoma (EC), pure parietal yolk sac (PYS) carcinoma and mixed parieto-visceral yolk sac carcinoma respectively. Cell lines NE and ME were composed of a monomorphous cell population; however, the morphology of ME was growth-medium-dependent. LRD was composed of a heterogeneous cell population and formed embryoid bodies. NE secreted soluble laminin, osteonectin, entactin and fibronectin but did not form visible pericellular matrix. ME formed pericellular matrix which was composed of laminin and entactin, but did not contain fibronectin. The LRD cells formed pericellular matrix which was composed of laminin, entactin and fibronectin. Whereas laminin from ME and LRD reacted with polyclonal antibodies and a monoclonal antibody to parietal yolk sac laminin, the laminin from NE cells was unreactive with the monoclonal antibody. Osteonectin was found in the supernatant of LRD and ME, but could not be demonstrated immunohistochemically in the extracellular matrix. We conclude that some extracellular matrix components, such as laminin and fibronectin, are produced not only by yolk sac carcinoma cells but by nullipotent EC as well, although the latter do not assemble them into extracellular matrix. Laminin produced by EC is immunochemically different from laminin secreted by yolk sac carcinoma. The extracellular matrix produced by mixed parieto-visceral yolk sac carcinoma is different from the matrix laid down by the pure PYS in that the latter does not contain fibronectin. The lack of osteonectin in the extracellular matrix of yolk sac carcinoma cells indicates that not all polypeptides secreted by these cell lines are incorporated into the extracellular matrix. The new cell lines described in this paper differ with regard to their capacity to form extracellular matrix and secrete its various components. Hence they could be used for further studies of basement membrane assembly in vitro. PMID- 2098283 TI - [Second look operation from the current viewpoint]. AB - Tumor reduction or elimination during primary surgery is the most important goal to aim at. Platinum-containing poly-chemotherapies led to an increase in remissions. However, highly advanced technologies (computed tomography, ultrasonography, nuclear magnetic resonance) and combined analysis of tumor markers are not sensitive enough to evaluate tumor-free status. A false-positive rate up to 33% at the time of second-look surgery was assessed in patients in clinical complete remission. Therapeutic second-look surgery with the purpose of tumor reduction is not capable to prolong the patient's survival time. Therefore, second-look surgery is limited to a diagnostic procedure, resulting in an objective assessment of newly developed therapy strategies. PMID- 2098284 TI - [Breast diseases within the scope of gynecology]. AB - Senology plays its special and important part in gynecology already. Beside the aim to keep contact with other specialists in different fields of medicine concerning breast diseases, it is the task of the senologist to treat the great number of patients and coordinate and promote training, teaching and science in this challenging area of medical interest. This includes also special activities in screening, medical checkup programs and patient information services. The First Clinic of Obstetrics and Gynecology in Vienna was the first clinic in Austria to start these activities. In 1973 a special outpatient unit for breast investigations was established. Since 1979 more than 1,100 cases of breast cancer have been operated and more than 3,500 breast operations in general have been performed, with also the corresponding postoperative treatment and care. PMID- 2098285 TI - [Effect of improved diagnosis on therapy]. PMID- 2098286 TI - [Ethics of the university teacher]. PMID- 2098287 TI - [Subspecialization in gynecology--pro and con]. AB - To discuss the problem of subspecialization in gynecology is very popular at present. Whether or not a complete separation into the three subdisciplines, (1) materno-fetal medicine--obstetrics, (2) surgical gynecology--gynecologic oncology, and (3) gynecologic endocrinology--reproductive medicine, is recommendable remains unclear. Some authors describe forms of supplementary postgraduate education only, a kind of prolongation of the basic gynecologic and obstetric training concentrating on one of the three main fields. The complete separation, i.e. into obstetric medicine, reproductive medicine, and gynecologic pelvic surgery, has the advantage of a more effective concentration on each of the respective subdisciplines in clinical work and in research. On the other hand, the separation will produce several disadvantages: (a) that which falls between the subdisciplines will be difficult to integrate; (b) the principle of the gynecologist functioning as a primary health care physician for women will be weakened, i.e. his competence in family-planning, pregnancy and delivery, cancer screening for genital and breast tumors, cycle disorders, pelvic inflammatory diseases and the care of postmenopausal women; (c) the lectures will become more split or overloaded with details than at present; (d) the need for a cost effective and widely available general gynecologic care will not be met, and (e) the opportunities for younger colleagues to have an office of their own will be restricted. The disadvantages outweigh the advantages. The solution might be a combination of the two competitive models: the creation of subdisciplines, completely separated from one another but for a minority only (i.e. to candidates for leading posts in clinics of the tertiary care, university hospitals etc).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098288 TI - [Choice of the surgical route in hysterectomy]. AB - At the Department of Obstetrics and Gynaecology of the University of Rostock there were no significant differences in morbidity and mortality in 2,811 abdominal hysterectomies and 2,030 vaginal ones in the years from 1970 to 1989, but the recovery of the patients after vaginal hysterectomy is better because of the intact abdominal wall. Therefore the vaginal route should be favoured if local conditions allow this. PMID- 2098289 TI - [Changes in obstetrics--retrospect and prospects]. AB - The panorama in obstetrics has completely changed during this century in our regions. It is characterized by a dramatic decrease of births, a high rate of deliveries in hospitals with extensive decentralization, obstetrical management by doctors with the assistance of midwives, a high level of technicalization, continuous improvement of the performances and an increase in legal regulations. PMID- 2098290 TI - IL-2 in the treatment of chronic myeloid leukemia after lymphoid blast crisis: a pilot study. AB - Five patients with lymphoid blastic transformation of chronic myeloid leukemia have been treated with IL2 associated with Vincristine (VCR) plus Prednisone (PDN). Our study indicates that IL2 may be employed in the management of this disease without excessive toxicity at the higher doses in hospitalized patients and at the lower doses as outpatients. Concerning the therapeutic efficacy, our preliminary results indicate that IL2 might be useful in enhancing the chemosensitivity of the leukemic blasts. It remains to be seen if this will result in a rapid return to the CP and in a prolongation of survival. PMID- 2098291 TI - Screening of beta-thalassemia mutations by PCR and ASO analysis in an Italian population of mixed geographic origin. AB - We used the polymerase chain reaction (PCR) and allele-specific-oligonucleotide hybridization (ASO) or restriction enzyme analysis (RE) to investigate the molecular defect in 100 Italian subjects heterozygous for beta-thalassemia, members of 50 couples at risk for the disease: 93 out of the 100 alleles studied were identified after investigating 9 known mutations. The mutation was identified in both members of the couple in 43/50 cases; in the remaining 7 couples the defect was identified only in one subject. The PCR-ASO or-RE method is a suitable, though still complex, approach to prenatal diagnosis of beta thalassemia in a population with heterogeneous molecular defects. PMID- 2098292 TI - Chromosome studies of enriched blast cell fractions in myelodysplastic syndromes terminating in acute myeloid leukemia. AB - For a better understanding of the karyotype evolution of different marrow cell populations in the course of MDS, 6 patients who eventually developed overt leukemia, belonging to a series of 46 MDS referred to our Institution, were studied ad diagnosis and at leukemic progression. In each case the blast cells were separated from the maturing precursors of the erythroid and granulocytic lineage by centrifugation on a Percoll density gradient. Parallel chromosome investigations were performed in each cell fraction. Cytogenetic analysis performed at presentation did not reveal distinctive karyotype features in metaphases arising in the blast enriched cell fraction, as compared with those obtained from the fraction containing erythroblasts and promyelocytes- myelocytes. These findings suggest that in the initial phase of MDS blast cells may lack distinctive cytogenetic features and may thus represent part of a clonal preleukemic proliferation. At the time of leukemia onset, clonal aberrations [trisomy 21 and del(11)(q23)] showing a restricted pattern of distribution within the blast cell enriched fractions were detected in two patients, whereas one patient showed an increase in size of the abnormal clone carrying monosomy 7, an aberration detected in metaphases obtained from both cell fractions. Thus, some evolutive steps in the natural history of these disorders can be heralded by the acquisition of chromosome aberrations more readily detectable in blast enriched cell fractions. In some cases, partial loss of differentiative capability by the abnormal clone may account for the detection, at leukemia onset, of chromosome aberrations involving both the blast cell fraction and the erythroblast promyelocyte enriched cell fraction. PMID- 2098293 TI - In vitro effects of bisantrene on fresh clonogenic leukemia cells: a preliminary study on 15 cases. AB - In vitro clonogenic assays may be useful for determining the sensitivity of leukemic cells to chemotherapeutic agents. We evaluated the antileukemic effect of Bisantrene (an anthracene derivative now undergoing phase II clinical trials in relapsed/resistant acute non lymphoid leukemias-ANLL) using the ANLL cell clonogenic assay. Fifteen cases were studied (9 newly diagnosed, 5 relapsed and 1 refractory ANLL). Normal CFU-GM sensitivity was tested in a subset of 10 normal controls. A wide range of concentrations (from 0.01 to 10 micrograms/ml) at 3 durations of exposure (30 min, 120 min, continuous) was employed. Bisantrene proved effective in 12 out of 15 ANLL cases, inhibiting blast colony growth (50% at 1 micrograms/ml; nearly 100% at 10 micrograms/ml) in a dose-dependent, time independent way. Three cases were unresponsive both in vitro and in vivo. Normal CFU-GM were inhibited at lower doses (50% at 0.5 micrograms/ml; 100% at 5 micrograms/ml). We conclude that: 1) Bisantrene is active in vitro on leukemic clonogenic cells at doses corresponding to plasmatic levels achievable in patients, with a parallel activity in vivo in 3 relapsed cases. It should be tested in vitro before therapeutic use in order to avoid, if possible, improper use in resistant patients. 2) Normal CFU-GM are more sensitive than clonogenic leukemic cells. This must be taken into account, in view of possible prolonged neutropenias after therapy. 3) The time-independent effect of the drug should be evaluated in the design of new therapeutic schedules. PMID- 2098294 TI - The syndrome of abnormal chromatin clumping in leucocytes: clinical and biological study of a case. AB - The authors report the clinical and biological findings of a case of a rare haematological malignant entity, morphologically characterised by a bizarre nuclear abnormality in granulocytes, consisting of exaggerated chromatin clumping and apparent fragmentation of the nucleus, with a loss of segmentation. They emphasize the coexistence of proliferative and dysplastic characteristics as a distinctive marker of this disorder and suggest it may represent a distinct rare morphological entity among the atypical chronic myeloid leukaemias, Ph1 and ber negative. PMID- 2098295 TI - Essential thrombocythemia: a retrospective study on the clinical course of 100 patients. AB - We report a study concerning 100 patients affected by essential thrombocythemia: 90 adult (age greater than 20 years) and 10 pediatric subjects. The diagnosis was made by chance (78%), because of hemorrhages (10%), thrombosis (9%), vasomotor symptoms (29%). In the adult group, single-agent chemotherapy was performed with good remission using pipobroman or interferon. Antiaggregant agents were used in all patients at diagnosis. During the clinical course only a few complications occurred. PMID- 2098296 TI - Ciprofloxacin for infection prophylaxis in granulocytopenic patients with acute leukemia. AB - Forty consecutive neutropenic patients with acute leukemia receiving oral ciprofloxacin (500 mg twice daily) and ketoconazole (200 mg daily) for selective intestinal decontamination were compared retrospectively with 33 comparable patients treated with polymyxin E (1,500,000 U x 3/day) and nystatin (1,000,000 U x 3/day). The incidence of febrile episodes was slightly lower in ciprofloxacin treated patients (87.5% vs 100%). No gram-negative sepsis was observed in this group compared with seven cases in patients receiving polymyxin E (p less than 0.01). Furthermore, eight patients in ciprofloxacin group (20%) had gram-positive sepsis, compared with five (15.5%) in the polymyxin E group. The incidence of documented fungal infections was similar in the two groups. Ciprofloxacin appears to be an effective agent for the prevention of gram-negative infections in granulocytopenic patients with acute leukemia, but may contribute to a shift in the type of infections in these patients towards those caused by gram-positive microorganisms, intrinsically fairly sensitive or with acquired drug resistance. PMID- 2098297 TI - Successful lectin-separated bone marrow transplantation in adenosine deaminase deficiency-related severe immunodeficiency. AB - Severe combined immunodeficiency disease (SCID) with adenosine deaminase (ADA) deficiency is a genetic autosomic recessive disorder with profound impairment of T-cell function, invariably complicated by fatal infections. The absence of ADA enzyme and the accumulation of deoxy-ATP, with toxic effects on the T-lymphocytes is the common feature of this disease. As a consequence, lymphoid precursors failure to develop into mature T-cells, resulting in absolute lymphopenia and atrophy of the thymus. Bone marrow transplantation from an HLA-identical donor is considered the treatment of choice for this disease. We describe the case of a 1 month-old child with ADA deficiency SCID who underwent bone marrow transplantation (BMT) using paternal haploidentical, lectin-separated marrow, as a source of hemopoietic stem cells. PMID- 2098299 TI - Thrombotic complications during L-asparaginase treatment for acute lymphocytic leukemia. AB - We report 2 new cases of thrombosis occurring in a cohort of 21 consecutive patients with acute lymphocytic leukemia treated with L-asparaginase (L-ase), 6,000 U/die s.c. or i.m. days 15-21 from start of chemotherapy, according to the GIMEMA LAL 0288 protocol. The first patient died of massive diffuse thromboembolism (thrombosis of sagittal sinus and of suprahepatic veins and pulmonary arteries; multiple hepatic and splenic infarctions) associated with markedly reduced levels of protein C, antithrombin III and plasminogen. In the second patient, portal vein thrombosis developed soon after the completion of L ase. Antithrombin III was reduced, whereas protein C level was normal. Therapy with fresh frozen plasma and subcutaneous calcium heparin (12,500 U twice daily) proved successful, and 8 days later abdominal echotomography revealed the complete disappearance of the thrombus. The incidence of thrombosis is similar to that previously found in a cohort of consecutive patients treated at our Department with a different schedule and dosage of L-ase administration, and similar to that reported in previous series. PMID- 2098298 TI - Accelerated hemopoietic recovery after chemotherapy and autologous bone marrow transplantation in hematological malignancies using recombinant GM-CSF: preliminary results obtained in 14 cases. AB - Human recombinant granulocyte-macrophage colony-stimulating-factor has been employed, on a compassionate basis, in 14 hematological patients in order to reduce the duration of the neutropenic period after high-dose chemotherapy for the treatment of hematological malignancies (7 traditional CHT courses, 7 autologous bone marrow transplantations). The compound was administered intravenously by 6-hour infusion at a dose of 5 microgram/kg/day until the patient reached at least 1000 PMN in the peripheral blood. Eleven out of the 13 evaluable patients showed a significative improvement in hemopoietic recovery, even though in CHT patients hematological reconstitution was higher in terms of PMN counts. The ABMT patients, however, showed a faster myeloid recovery than that obtained both in a group of 14 NHL and in a series of 8 MM previously submitted to ABMT in our Institution. Moreover the increase in peripheral neutrophils appeared to be stable, since it was maintained throughout one month after the end of rhGM-CSF therapy. We did not observe effects on platelet or erythrocyte recovery. We conclude that rhGM-CSF is active in accelerating the recovery of myelopoiesis, without significant toxic or collateral effects. PMID- 2098300 TI - Stiff-man syndrome in a patient with Hodgkin's disease. An unusual paraneoplastic syndrome. AB - A case of stiff-man syndrome (SMS), a rare and dramatic CNS disease characterized by continuous muscle activity and painful spasms resembling a chronic form of tetanus, occurring in a patient with Hodgkin's disease (HD) is reported. The patient developed the clinical features of SMS at the same time as the HD relapse. A satisfactory improvement was obtained with diazepam, but the complete recovery from stiffness was achieved only after chemotherapy was started. Cerebellar autoantibodies were found in the serum of the patient. With chemotherapy the patient achieved a second complete remission (CR). Eighteen months later the patient developed a second HD relapse, and at that time no signs of SMS were detected. PMID- 2098301 TI - Analysis of the breakpoint cluster region in essential thrombocythemia. AB - Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by a platelet count higher than 1000 x 10(9)/l. Bone marrow karyotype aberrations are occasionally observed. The presence of cytogenetic and molecular markers of chronic myeloid leukemia (CML) was assessed in 25 patients with the clinical features of ET. One displayed a complex translocation (9; 15; 22) (q34.1 or q34.3; q26.1; q11), and another a Philadelphia chromosome with standard translocation (9; 22) (q34; q11). Southern blot analysis revealed a rearranged breakpoint cluster region (bcr) in each case. Both patients experienced a stormy disease course without a leukemic transformation. These data indicate that the Philadelphia chromosome rarely occurs in ET and strongly influences patient outcome. PMID- 2098302 TI - Consolidation treatment with dexamethasone and alpha-2B recombinant interferon further reduces the M-component level in multiple myeloma patients responding to conventional induction chemotherapy. AB - Three patients with symptomatic multiple myeloma who had achieved an objective response after conventional induction chemotherapy were treated with alpha-2b interferon plus intermittent high-dose dexamethasone as consolidation therapy. This treatment included three mega units of alpha-2b-interferon three times a week, plus 4 days pulsed high-dose dexamethasone every 28 days for 6 months. Toxicity was limited to a mild flu-like syndrome. A further and significant M component reduction (50%), obtained after conventional chemotherapy, suggests the value of intermittent high-dose dexamethasone plus interferon as consolidation therapy. PMID- 2098304 TI - Prevalence of folate deficiency in beta and delta-beta heterozygous thalassemia. PMID- 2098303 TI - Proliferative activity in non-Hodgkin's lymphomas and chronic lymphocytic leukemias as determined on cytological samples by Ki 67 monoclonal antibody. PMID- 2098305 TI - 1,25(OH)2D3 and TPA in vitro activity on B-CLL. PMID- 2098306 TI - Beware before concluding: one anemia can hide two others. PMID- 2098307 TI - Interferon alpha-2b in the treatment of myelofibrosis. PMID- 2098308 TI - More than one form of HIV-related thrombocytopenia. PMID- 2098309 TI - Dilated cardiomyopathy: chronic viral infection or autoimmune disease? A critical view of the viral and the autoimmune hypotheses. PMID- 2098310 TI - Secondary prophylaxis with antiarrhythmic agents in survivors of myocardial infarction. PMID- 2098311 TI - Clinical and hemodynamic profile of patients with calcific mitral valve disease. AB - Clinical, hemodynamic and fluoroscopic findings were analysed in 1123 patients with rheumatic mitral valve disease. The incidence of mitral valve calcification was 15 percent (mild 3 percent, moderate 9 percent, and severe 3 percent). There was a male preponderance (male 17 percent, female 5 percent). The presence of moderate to severe degree of calcification of mitral valve correlated with age, rhythm, transmitral gradient, associated mild mitral regurgitation, pulmonary artery pressure, systemic embolisation and previous commissurotomy. No correlation was found between the degree of calcification and presence or absence of other valve lesions. PMID- 2098312 TI - Clinical and haemodynamic effects of oral metoprolol therapy in dilated cardiomyopathy. AB - The clinical and haemodynamic effects of oral metoprolol therapy were assessed in thirty patients of dilated cardiomyopathy, aged 14-58 (33 +/- 10.9) years. After baseline haemodynamic study, metoprolol was administered in a dose of 25-100 mg/day (mean 87.0 +/- 25.1 mg/day). Before start of therapy, 13 patients were in NYHA symptom class IV, 14 were in NYHA class III and 3 were in NYHA class II. Symptomatic improvement was seen on oral metoprolol therapy in all patients except one. Six months after therapy 13 patients were asymptomatic, 16 were in NYHA class II, while 1 patient continued to be in NYHA class III. Repeat haemodynamic study in 15 patients done at a mean of 5.7 months showed a significant fall in the right ventricular end diastolic pressure (from 9.1 +/- 4.4 to 5.7 +/- 2.9 mm Hg, p less than 0.01), mean pulmonary artery pressure (from 32.3 +/- 13 to 24.5 +/- 10.3 mmHg, P less than 0.01) and mean pulmonary capillary pressure (from 23.3 +/- 10.3 mmHg to 14.7 +/- 7.4 mmHg, P less than 0.01). The left ventricular ejection fraction increased from 18.8 +/- 6.3 to 24.0 +/- 7.3 per cent, (P less than 0.05), while no significant change was observed in the cardiac index (2.43 +/- 0.47 to 2.66 +/- 0.83 L/min/m2, p = NS). These data suggest improvement in diastolic and systolic left ventricular function after metoprolol therapy. PMID- 2098313 TI - Immunohistochemical characterization of Aschoff nodules and endomyocardial inflammatory infiltrates in resected left atrial appendages. AB - Presence of Aschoff nodules and other chronic inflammatory cells in the left atrial appendage even in the absence of rheumatic activity has been reported in a high percentage of patients with chronic rheumatic valvular heart disease. This study was conducted on 37 left atrial appendages resected at the time of closed mitral valvotomy. Aschoff nodules were present in 61.2 percent of resected appendages, positivity being 71.4 percent in the age group of 20 years of less and 53.3 percent in patients more than 20 years of age. The histological findings did not change significantly in the presence of activity. The frequency of Aschoff nodules and chronic inflammatory cells and their subtypes also did not show any correlation with age, sex, duration of symptoms or severity of mitral stenosis. PMID- 2098314 TI - Surgical management of coarctation of aorta. AB - Between 1961 and 1988, 68 patients underwent operation for coarctation of the aorta. The average age of presentation of these subjects was higher than in other series. 7.1 percent were asymptomatic, a finding which is not seen in reports from the west. Operative procedures included resection and end to end anastomosis, resection and graft interposition, bypass grafting, patch aortoplasty and subclavian flap aortoplasty. However, the technique of patch aortoplasty, routinely performed in the last 24 years of this series seemed by far the most satisfactory procedure. Subclavian flap aortoplasty was carried out in a selected group of younger children. Associated cardiac anomalies influenced the results adversely. The overall operative mortality was 5.8 percent. Hypertension did not regress in 11.7 per cent of patients inspite of a successful operation as judged by the return of peripheral pulses in the lower limbs. Re coarctation was not seen in this series. The overall results of operation for coarctation of the aorta have been very satisfactory and comparable with those in other published series. PMID- 2098315 TI - Evaluation of left ventricular function during roentgen contrast ventriculography. AB - Changes in the left ventricular (LV) function during direct ventriculography (contrast medium injected into LV cavity) and during intravenous left ventriculography (contrast medium injected into right atrium) were assessed in 22 normal subjects. During angiography the left ventricular pressure was continuously recorded by a microtip manometer catheter. LV images and pressure curves were analysed by a computer analysis system. The forceful intraventricular injection of contrast medium during the direct ventriculogram resulted in significant changes in the LV diastolic function, and increased LV pressure and LV working parameters. Mechanical efficiency of the LV contraction decreased. Acute volume overload of the left ventricle appears to be the main limitation of this method. To overcome this limitation, we recommend the use of intravenous biventriculography with simultaneous recording of LV pressure, instead of direct ventriculography. This modification with subsequent frame to frame analysis of the study results may be used successfully in clinical research trials. PMID- 2098316 TI - Right ventricular filling abnormalities in acute inferior wall myocardial infarction--a pulsed Doppler study. AB - Pulsed Doppler derived velocity profile of right ventricular filling was used to assess right ventricular diastolic function in 29 patients with acute inferior wall myocardial infarction. The peak velocities of the early filling wave 'E' and the atrial wave 'A' were measured. Diastolic dysfunction, defined as E/A ratio less than 1.0, was seen in 15 patients. Of these 15 patients, 9 had electrocardiographic evidence of right ventricular infarction and only 6 had clinical evidence of right ventricular failure. None of the 14 patients without right ventricular diastolic dysfunction (E/A ratio more than 1.0) had electrocardiographic evidence of right ventricular infarction or clinical evidence of right ventricular failure. Pulsed Doppler appears to be a sensitive technique in identifying hemodynamic derangements induced by right ventricular infarction. PMID- 2098317 TI - Coxsackie viral myocarditis: a clinical and echocardiographic study. AB - Thirty two patients with acute onset of cardiac symptoms following an episode suggestive of viral infection, were studied. 11 patients had Coxsackie viral myocarditis. All had 4 fold rise of neutralising Coxsackie viral antibody titres on paired sera tested. Coxsackie B virus types 2 and 4 were commonly detected. Among the eleven patients, 8 presented with congestive heart failure, 2 with ventricular arrhythmias and one with chest pain and S3 gallop. All had ECG changes. Echocardiographic examination showed global left ventricular dysfunction in 7, regional wall motion abnormalities in 2 and normal left ventricular function in one. Serial echocardiographic examination showed progressive myocardial dysfunction in 3 and improvement in myocardial function in two patients. Two patients died during the follow up period. Echocardiography helped in assessing the course of patients with viral myocarditis. PMID- 2098318 TI - Safety of use of antiarrhythmic drugs. PMID- 2098319 TI - Post traumatic ventricular septal defect. PMID- 2098320 TI - The spectrum of isolated ocular reactions following intravascular contrast administration. AB - Five out of 2930 (0.2%) consecutive patients developed ocular adverse reactions following intravascular administration of sodium-meglumine diatrizoate. The adverse reactions included bilateral blurring of vision (2), unilateral orbital oedema (2) and bilateral intense conjunctival congestion (one patient). The latter two phenomena responded to steroid and antihistaminic agents. Contrast medium-induced ocular anaphylactoid response is rare but clinically significant. PMID- 2098321 TI - Cor-triatriatum with atrial septal defect and bicuspid aortic valve diagnosed by cross-sectional echocardiography. AB - We report a rare case with a combination of cor-triatriatum, large secundum atrial septal defect and bicuspid aortic valve. The diagnosis was made by cross sectional echocardiography. A defect was present between proximal (accessory) left atrial chamber and right atrium decompressing the accessory left atrial chamber. The large left to right shunt resulted in severe pulmonary arterial hypertension. PMID- 2098322 TI - Antibody response to immunization with purified GD3 ganglioside and GD3 derivatives (lactones, amide and gangliosidol) in the mouse. AB - GD3 is the ganglioside most abundantly expressed on the cell surface of human melanoma, and treatment with a monoclonal antibody recognizing GD3 has induced major responses in a small proportion of patients. However, we have been unable to induce production of GD3 antibodies in melanoma patients by active immunization with GD3-expressing melanoma cells or purified GD3. In this report we describe attempts to increase the immunogenicity of GD3 in the mouse by chemical modification. GD3 lactone I and II, GD3 amide and GD3 gangliosidol were synthesized, and the humoral immune response to these derivatives was compared with the response to unmodified GD3. The GD3 derivatives were more immunogenic than GD3. At a low dose all congeners induced an IgM response, with antibody titers higher than those elicited by low-dose GD3. The gangliosidol and amide derivatives also induced an IgG response. IgM antibodies induced by immunization with GD3 lactone I cross-reacted with purified GD3 and GD3-expressing melanoma cells. Titers of GD3 cross-reactive antibodies were slightly higher than after immunization with GD3 itself at the same low dose. IgM and IgG antibodies induced by the other congeners did not cross-react with GD3. PMID- 2098323 TI - The splenic pool of mouse stem cells: in vitro differentiation and expression of the BP-1 alloantigen on cells of the lymphoid and myeloid lineages. AB - The relative paucity of data about the development of the stem cell pool present in the spleen prompted this study. During in vitro cultures of B-enriched lymphocytes from mouse spleens and in the presence of a culture supernatant of WEHI-3 cells (WEHI-SUP), a population of cells expressing the BP-1 antigen appears progressively, reaches an optimal size 8 days after initiation of the culture, and disappears on day 28. In 8-day-old cultures, a minor population of cells bearing both BP-1 and B220 can be detected. The growth of this cell population, with characteristics of the B lymphoid lineage (pro-B), is strictly dependent on the presence of WEHI-SUP in the medium. After 2 weeks of culture, the BP-1 antigen is expressed on a cell population, which is essentially constituted of B220-, polynuclear cells. The BP-1 antigen, which is considered as characteristic of early cells of the B lymphoid lineage, can therefore also be expressed on cells of the myeloid lineage. The injection of BP-1+ or B220+ cells in irradiated mice can hardly reconstitute their B cell pool, whereas BP-1- and B220- cells are much more efficient in vivo progenitors of this cell lineage. PMID- 2098324 TI - Characterization and expression of the antigen present on resident rat macrophages recognized by monoclonal antibody ED2. AB - Because of the absence of a specific marker for labeling resident macrophages in the rat, there is almost no information available regarding the properties of individual resident macrophages in different organs. The recently described and in our laboratory developed mAb ED2, has been shown to exclusively recognize resident macrophages. The present study examines expression, function and structure of the ED2 antigen to obtain more information about the marker and therefore, more information about resident macrophages. In earlier studies, the expression of ED2 could not be induced by a range of macrophage stimulating factors under non-adherent culture conditions. We show a highly inducible expression of the ED2 antigen under adhering, non proliferating conditions as well as in long-term bone marrow cultures. ED2 appears to recognize a surface protein on resident macrophages consisting of three protein chains of 175, 160, and 95 kDa. PMID- 2098325 TI - Interaction of osteogenic cells with hydroxylapatite implant materials in vitro and in vivo. AB - In a series of scanning electron microscopic studies, the reaction of osteogenic cells to hydroxylapatite (HA) implant materials was investigated in culture and following implantation. Tissue components as found in normal rat and dog bone were identified at the interface in both test systems. In vivo, implant bed cells showed an intimate contact with the HA surfaces. Osteoblasts deposited organic matrix and bone mineral in direct apposition to HA, with no evidence of encapsulation or granulation tissue. The development of such a direct spatial relationship appears to involve mechanisms more encompassing than epitaxis. PMID- 2098326 TI - Histologic comparison of ceramic and titanium implants in cats. AB - This study compared the reparative processes around cylindrical glass-ceramic coated and pure titanium implants placed in feline femurs. Six weeks after implant placement, bone specimens with inserted implants were prepared for histologic examination including histomorphometric quantification of the relative implant surface areas that were in contact with bone. The glass-ceramic implants were surrounded by a 0.2- to 0.5-mm envelope of fibrous connective tissue [corrected]. By contrast, the major part of the titanium implants (81% +/- 5%) was in direct contact with living lamellar or woven bone. Thus, titanium and glass ceramic evoked different reparative processes when implanted in bone, and only the titanium implants appeared to become osseointegrated. PMID- 2098327 TI - Reconstruction of severely resorbed edentulous maxillae using osseointegrated fixtures in immediate autogenous bone grafts. AB - A surgical technique for rehabilitation of severely resorbed edentulous maxillae using fixed prostheses or overdentures supported by osseointegrated fixtures in immediate autogenous corticocancellous bone grafts from the ilium is described. The results of the first 23 consecutively treated patients are reviewed. The mean observation time was 4.2 years (range 1 to 10 years). A total of 124 fixtures was originally placed into the grafts, supplemented with 16 fixtures inserted later into seven of the jaws. Throughout their observation period, 17 of the patients had continuously stable prostheses. The remaining five had overdentures, and one patient had resorted to a conventional complete denture. After 4 years, 12 of 16 patients had continuously stable prostheses. Corresponding values at 5 years were 7 of 8 patients. Calculated from the date of abutment connection, 82.1% and 81.6% of the original fixtures were clinically stable and radiographically osseointegrated after 4 and 5 years in function, respectively. From the date of fixture placement, the corresponding figures were 75.3% and 73.8%, respectively. The mean marginal bone loss after the first year of prosthesis function was 1.49 mm. The annual marginal bone loss thereafter was about 0.1 mm. The results indicate that this technique is worthwhile for patients with extreme maxillary atrophy and who cannot wear conventional complete dentures. PMID- 2098328 TI - Characterization of the subgingival microbial flora around endosteal sapphire dental implants in partially edentulous patients. AB - The microbiota associated with oral endosteal sapphire ceramic implants was studied using cultural methods. Samples were taken from both implant and control (tooth) sites, and comparisons were made between healthy and diseased and between implant and control sites. Diseased sites harbored a microbiota with a large number and proportion of Gram-negative anaerobic rods, black-pigmented Bacteroides, and surface translocating bacteria. Healthy sites in the same patients had smaller amounts of bacteria dominated by facultative Gram-positive cocci and rods. The microbiota in diseased and healthy implant and control sites was very similar. It is suggested that peri-implant tissues behave very similarly to periodontal tissues and that peri-implantitis lesions should be considered as site-specific infections harboring a high number of periodontal pathogens, mainly Gram-negative anaerobic rods. PMID- 2098329 TI - Oxide thickness and surface contamination of six endosseous dental implants determined by electron spectroscopy for chemical analysis: a preliminary report. AB - Electron spectroscopy and argon ion etching were used to determine the depth and composition of the oxide layers of six competitive dental implant systems. To minimize problems associated with analyzing the active oxide layers, the implants were removed from their original packaging in an oxygen-free environment. The majority of the six implant systems were found to have similar oxide thickness in the range of 20 to 34 A. Some variation was found in the extent of non-oxide surface contamination. PMID- 2098330 TI - Applicability of osseointegrated oral implants in the rehabilitation of partial edentulism: a prospective multicenter study on 558 fixtures. AB - Nine clinical centers using the Branemark System participated in a prospective study of 159 partially edentulous patients between 18 and 70 years of age. Clinical parameters evaluated were plaque index, gingivitis, pocket depth, bleeding index, tooth mobility, and stomatognathic function. Initially, 558 fixtures were placed and 521 remained in the study following prosthesis placement (199 prostheses in 154 patients). Fixtures were lost or unaccounted for because of nonintegration prior to prosthesis fabrication (19), patient withdrawal (11), prosthodontic reasons (6), and failure during prosthetic procedures (1). Failure was primarily attributable to unfavorable bone quality, sex (more in males), and smaller fixture size. Complications and failure related to other patient characteristics are presented. After 1 year of a 5-year study, preliminary results suggest that a success rate equal to or better than that obtained with edentulous patients may be expected. PMID- 2098331 TI - Magnetic resonance imaging as an adjunctive diagnostic aid in patient selection for endosseous implants: preliminary study. AB - The use of magnetic resonance imaging as an adjunctive aid to determine the amount of bone available and the anatomic limitations for the placement of endosseous dental implants is introduced. Advantages and disadvantages are discussed. The results suggest that magnetic resonance imaging can provide, without the need for a reformatting software program, adequate information concerning the amount of bone and anatomic limitations for placement of endosseous implants in the mandible and maxilla. PMID- 2098332 TI - Use of two implant systems within the same restorative segment: a clinical report. AB - The incorporation of more than one dental implant system within the same restorative segment may be a reliable approach to treatment. This article describes a clinical situation that was resolved, after the failure of a pre existing subperiosteal implant, by the use of both subperiosteal and osseointegrated fixtures concurrently. The result was an increase in stability, and it is hoped that restoration settling will be minimized. PMID- 2098333 TI - Atraumatic removal of teeth and root fragments in dental implantology. AB - A technique that facilitates the removal of teeth or retained root fragments without traumatizing the alveolar bone of the socket is described. This technique may be employed whenever such extractions are envisaged, but it is particularly important when the subsequent placement of dental implants is planned. PMID- 2098334 TI - Improved visibility with the 'Van Ooy' lip and cheek retractor. PMID- 2098335 TI - Bactericidal effects of human neutrophils and sera on selected endodontic pathogenic bacteria in an anaerobic environment. AB - Phagocytosis by normal human neutrophils and the bactericidal activity of normal human pooled serum were measured under anaerobic conditions on six endodontic pathogenic bacterial species from the genera Actinomyces, Bacteroides, Fusobacterium, Peptostreptococcus and Streptococcus. The results revealed that Actinomyces viscosus was not killed either by human neutrophils or by 20 per cent serum; Peptostreptococcus anaerobius was not killed by either 20 per cent or 95 per cent serum; and Bacteroides intermedius was susceptible to both 20 per cent and 95 per cent serum, but was not killed by neutrophils after exposure for 20 minutes. The other species showed intermediate susceptibility patterns. Such results suggest that oral pathogens vary with regard to the bactericidal effects of these two host defense mechanisms, and that this variation may at least in part explain the relative quantities of microbes recovered in certain oral infections. PMID- 2098336 TI - Penetration of dentine by three oral bacteria in vitro and their associated cytotoxicity. AB - Three common oral bacteria, namely Streptococcus sanguis, Actinomyces viscosus and Corynebacterium spp. were studied with regard to their ability to penetrate etched and unetched dentine and for their effect on underlying cell cultures. The test organisms were grown in cylinders above dentine slices 100 and 500 microns thick for 72 hours. The slices were in contact with tissue culture medium covering a layer of fibroblasts. Penetration of 100 microns slices was most rapid with S. sanguis, followed by A. viscosus and Corynebacterium. The pattern was similar but slightly delayed when 500 microns slices were used, but in most cases penetration had occurred by 72 hours. The presence of a smear layer had no effect on the results obtained. Following penetration, cell destruction was most extensive with S. sanguis, the most cytotoxic organism, followed by Corynebacterium and A. viscosus. In the limited number of dishes where no penetration occurred there was little effect on cell numbers. PMID- 2098337 TI - Comparison of subcutaneous connective tissue responses among three different formulations of gutta-percha used in thermatic techniques. AB - A study of the subcutaneous connective tissue response of 24 white rats to three different formulations of gutta-percha was undertaken. The prepared specimens were examined under the light microscope after intervals of 7, 21, 60 and 120 days. The results showed identical tissue responses after the initial period of 7 days. However, after 120 days the gutta-percha supplied with the Ultrafil system presented mature granulation tissue with neither oedema nor vascular congestion, in contrast to the responses observed with the McSpadden and Obtura formulations. PMID- 2098338 TI - Tissue response to glass ionomer retrograde root fillings. AB - The periapical tissue response to glass ionomer cement retrograde root fillings was investigated both in the presence and in the absence of fillings in the root canals of eight upper incisor teeth of four monkeys. The pulps of the teeth were extirpated and one canal in each pair was filled with laterally condensed gutta percha immediately after canal preparation. The other canal was prepared but left open to oral contamination. Apicectomies were performed on both teeth in each pair 1 week later, and glass ionomer cement retrograde root fillings were placed. After 5 months, the teeth and surrounding tissues were removed and prepared for histological examination. All four of the teeth without root canal fillings showed severe periapical inflammation, and bacterial were present in the interface between the dentine and the retrograde root filling. The teeth with root canal fillings showed little or no periapical inflammation. This study showed that adhesive retrograde root fillings were successful when the root canal was completely filled, but in the absence of a gutta-percha canal filling they failed to provide a seal. PMID- 2098339 TI - Investigation into the apical leakage of root-filled teeth prepared for a post crown. AB - The effect of post canal preparation on the apical seal of endodontically treated teeth was studied in vitro. Single-rooted teeth with mature apices were prepared chemomechanically and obturated with gutta-percha and sealer using one of four techniques: cold lateral condensation, thermo-mechanical compaction, thermomechanical compaction as an adjunct to lateral condensation (hybrid technique), or lateral condensation using an electrically heated spreader, the Endotec. Forty-eight hours after obturation each group of 15 teeth was prepared to accept a post crown. Five teeth in each group were left unprepared as controls. The extent of apical leakage was then determined using a dye, Indian ink, and a clearing technique that rendered the teeth transparent. Linear measurement of the dye penetration was recorded. The results showed that, for each method of obturation, there were no statistically significant differences between the teeth prepared for a post and the unprepared controls. There were no significant differences in leakage between the different groups that had been prepared for a post, or between the control groups. PMID- 2098340 TI - Quantitative microleakage study on a new retrograde filling technique. AB - An in vitro endodontic leakage model was used to compare the sealing ability of conventional retrograde amalgam fillings with a new retrograde filling technique by measuring dye leakage quantitatively. The new technique consisted of retrograde preparation of the root canal using the Endocursor, an endodontic handpiece. The canal was then filled with sealer and injection-moulded gutta percha, using either the Hygenic Ultrafil system or the Unitek Obtura method. In both cases the gutta-percha was vertically condensed and subsequently cold burnished. The two experimental groups and the amalgam group each consisted of 20 extracted human canine teeth and lower premolars. The results were analysed statistically by ANOVA and a Student-Newman-Keuls multiple comparison test. After 1 week at 37 degrees C, very little leakage was observed in the amalgam and gutta percha groups. After a second week, during which leakage was enhanced by gas pressure, leakage in the amalgam group was significantly greater than that in the gutta-percha groups (P less than 0.01). There were no significant differences between the two experimental gutta-percha groups. It is concluded that the new retrograde filling technique causes less leakage than the conventional amalgam retrograde filling technique in an in vitro model. PMID- 2098341 TI - Standardized technique for linear dye leakage studies: immediate versus delayed immersion times. AB - A dye leakage study was performed in vitro to compare the extent of leakage into root canals obturated with gutta-percha following immediate versus delayed immersion in Indian ink. Sixty extracted human teeth with single canals were instrumented and obturated with gutta-percha and sealer. Each group of 20 teeth was then immersed in the ink either immediately after obturation or after a delay of 1 or 7 days. After 7 days in Indian ink, the teeth were rendered transparent by clearing, and the linear extent of ink penetration was measured with a stereomicroscope. Complete leakage was observed in the two positive control teeth, and no leakage was evident in the two negative controls. Statistical analysis of the results indicated that there was no significant difference in leakage between the three experimental groups. PMID- 2098342 TI - Extensive bone loss associated with periapical infection with Bacteroides gingivalis: a case report. AB - A case is presented in which rapid and extensive bone loss occurred around a maxillary molar with periapical infection by Bacteroides gingivalis (Porphyromonas gingivalis). The lesion failed to respond to conventional endodontic therapy. An adjacent vital molar was extracted and an unfavourable periodontal condition occurred despite microbiological investigation and surgery. PMID- 2098343 TI - In vivo findings associated with heat generation during thermomechanical compaction of gutta-percha. 1. Temperature levels at the external surface of the root. AB - Temperature elevations of 10 degrees C above body temperature, of duration greater than 1 minute, may be sufficient to cause bone tissue injury. Temperature rises on the root surface in excess of 10 degrees C have been shown in studies in vitro of thermoplasticized gutta-percha root filling techniques. To determine whether results in vitro at room temperature could be extrapolated to conditions in vivo, temperature elevations were recorded at the mid-point on the root surface of the canine tooth in the ferret during thermomechanical compaction of gutta-percha. The time taken for the temperature to return to normal was also measured. There was no statistically significant difference between temperature elevations recorded in vitro and those measured in vivo. A linear extrapolation may therefore be made from results recorded at room temperature. Temperature elevations dissipated more rapidly in vivo than in vitro; this may be due to the cooling effect of the microvasculature of the periodontal membrane. PMID- 2098344 TI - In vivo findings associated with heat generation during thermomechanical compaction of gutta-percha. 2. Histological response to temperature elevation on the external surface of the root. AB - An in vivo investigation is described and a histological evaluation made of the effect of canal obturation by thermomechanical compaction of gutta-percha and sealer on the cementum on the lateral surface of the root and adjacent periodontal membrane and alveolar bone of the ferret canine after time intervals of 24 hours, 20 days and 40 days. These tissue reactions were compared with those in the roots of control teeth filled by lateral condensation of cold gutta-percha and sealer. Iatrogenic damage was apparent in a minority of the experimental specimens 20 and 40 days after obturation. PMID- 2098345 TI - Review of calcium hydroxide. AB - Calcium hydroxide is a material which has been used for a variety of purposes since its introduction into dentistry in the early part of the twentieth century. In its pure form, the substance has a high pH, and its dental use relates chiefly to its ability to stimulate mineralization, and also to its antibacterial properties. A range of products has been formulated with different therapeutic actions, the effects of which are partially dependent upon the tissue to which they are applied. The material is reviewed under the following general headings: biochemical actions; dental formulation; uses. PMID- 2098346 TI - Retrieval of silver cones using different techniques. AB - Three different techniques of silver cone retrieval were investigated in 41 teeth containing 91 silver cones. The techniques used for retrieval were as follows: (i) hand instrumentation with files, spoon excavators and forceps; (ii) the automated Canal-Finder-System; (iii) ultrasonic devices. In all teeth, these techniques were used in the same sequence, starting with hand instrumentation, followed by the Canal-Finder-System, and ending with ultrasonic devices. Fifty two of the 91 cones (57 per cent) could be removed with hand instruments. Of the remaining 39 cones, 19 were removed after using the Canal-Finder-System. An additional 10 cones could be removed after the use of ultrasonics. Two cones could only be bypassed by the Canal-Finder-System but were not removed with any of the techniques investigated in this study. Eight silver cones (9 per cent) could neither be bypassed nor removed. It was concluded that silver cone retrieval in more than half the cases could be performed easily with hand instruments, particularly spoon excavators. The automated Canal-Finder-System and ultrasonics proved to be helpful devices in many difficult cases, but did not guarantee success in every case. PMID- 2098347 TI - In vitro study to compare impact fracture resistance of intact root-treated teeth. AB - The aim of this in vitro study was to determine the effect on impact fracture resistance of three methods for restoration of root-treated lower incisor teeth with otherwise intact natural crowns. In a control group (Group I) laterally condensed gutta-percha filled the entire root canal, whereas part of the root filling was removed to enable insertion of a 1 mm diameter post in the other two groups. Stainless steel posts were placed in Group II and experimental carbon fibre reinforced carbon (CFRC) in Group III. A composite resin luting agent was used to lute the posts, and standardized composite resin restorations were placed in each access cavity. Fifteen specimens of each group were tested to failure with a single impact force applied at 90 degrees to the mid-point inciso cervically on the labial surface. The peak force, peak energy, and first peak total energy required to fracture each specimen were recorded. The results showed no significant difference between the three groups, nor was a difference in the mode or site of fracture observed. The results suggested that there is no advantage from the point of view of fracture mechanics in 'restoring' intact root treated teeth with either stainless steel or carbon fibre reinforced carbon rods. PMID- 2098348 TI - Reattachment of the periodontium after tooth movement into an osseous defect in a monkey. 1. PMID- 2098349 TI - Use of orthodontic therapy to alter infrabony pockets. 2. PMID- 2098350 TI - Overlapped flap: a surgical modification for implant fixture installation. PMID- 2098351 TI - Thick gingival autograft for the coverage of gingival recession: a clinical evaluation. PMID- 2098352 TI - Differential treatment planning for the single anterior crown. PMID- 2098353 TI - Bioesthetics of complete porcelain occlusal rehabilitation using the Sunrise ceramic system: a case report. PMID- 2098354 TI - Clinical and histologic evaluations of HTR alloplastic grafting material: case reports. PMID- 2098355 TI - Periodontal bone graft technique. PMID- 2098356 TI - Comparison of the soft and osseous tissue responses of loaded and unloaded IMZ implants. PMID- 2098357 TI - Treatment of gingival pigmentation and discoloration for esthetic purposes. PMID- 2098359 TI - Advances in periodontal disease diagnosis. PMID- 2098358 TI - 3-year followup study of early single implant restorations ad modum Branemark. PMID- 2098360 TI - Guided tissue regeneration for implants placed into extraction sockets and for implant dehiscences: surgical techniques and case report. PMID- 2098361 TI - Effects of a 1% chlorhexidine gel (corsodyl) on the bone resorption and inflammation associated with experimentally induced periodontitis in dogs. PMID- 2098362 TI - Tissue response under hyperpressure from Convex pontics. PMID- 2098363 TI - Histologic evaluation of cementogenesis on periodontitis-affected roots in humans. PMID- 2098364 TI - Copings on tooth and implant abutments for superstructure prostheses. PMID- 2098365 TI - Plaque retention on Dicor crowns and gingival health evaluated over a 4-year period. PMID- 2098366 TI - Expanded applications of DentaScan (multiplanar computerized tomography of the mandible and maxilla). PMID- 2098367 TI - The transpositioned flap in mucogingival surgery. PMID- 2098368 TI - In-vitro preparation of experimental models of hepatitis with D-galactosamine and their modification by liver-repairing factors. AB - Hepatocytes, isolated from male F344/DuCrj rats by means of perfusion with collagenase, were incubated in Williams E medium containing newborn calf serum (PFCS), insulin, dexamethasone and D-galactosamine. The resulting liver-cell damage was confirmed by MTT assay to be dependent on the dose of D-galactosamine. This damage was clearly modified by the addition to the medium of the liver repairing factors which appeared in serum in the initial stage of liver damage resulting from either partial hepatectomy or administration of D-galactosamine (Gal-N) in rats. When a massive number of splenocytes from normal rats was injected into the caudal vein of rats with liver damage caused by D galactosamine, liver-damage-repairing factors were induced in the serum which were found to exert a particularly strong inhibition of the damage to hepatocytes caused by D-galactosamine when incubated in vitro. PMID- 2098369 TI - Biological activity of two photoactive benzocoumarins. AB - The effect on DNA synthesis in cell cultures exerted by two photoactive benzocoumarins were studied. A favourable ratio between inhibition of DNA synthesis and the irradiation time periods was found in these compounds. This activity is substantially due to their ability to produce a monofunctional adduct with DNA. PMID- 2098370 TI - Cholinergic muscarinic and nicotinic binding by human lymphocytes: differences between peripheral blood cells and cultivated cell lines. AB - Kinetic and equilibrium studies of [3H]QNB and [3H]nicotine binding to human peripheral blood lymphocytes have been performed. The calculated number of muscarinic binding sites is 6 x 10(4) per cell, and of nicotinic binding sites is 2 x 10(3) per cell. The conditions for routine estimations of muscarinic and nicotinic receptors on human lymphocytes have been established. Significant differences in the distribution of muscarinic and nicotinic binding sites among normal PBL and malignant cell lines have been described. PMID- 2098371 TI - Ultrastructural changes of human amniotic cells induced by natural human interferon-alpha. AB - Human interferon-alpha (Hu-IFN alpha) and phorbol myristate acetate (PMA), a direct activator of protein kinase C (PK-C), induce the translocation of protein kinase C from the cytosol to the membrane fraction. By the use of transmission (TEM) and scanning (SEM) electron microscopy we have shown that treatment of human amniotic cells (UAC) with Hu-IFN alpha resulted in profound changes in the shape, volume and ultrastructure of the cells. Most treated cells had enlarged nuclei with marginal condensation of chromatin. Nucleolar segregation, disintegration and clumping of nucleolar components were also observed. The number of interdigitating cell processes decreased and the cell surface microvilli became shortened. Similar ultrastructural alterations were induced by PMA also. All these functional and morphological data strongly support the hypothesis that protein kinase C is a key factor in IFN-mediated cell reactions. PMID- 2098372 TI - Evolution of superficial vein thrombosis treated with defibrotide: comparison with low dose subcutaneous heparin. AB - Forty patients with superficial vein thrombosis (SVT) or thrombophlebitis were randomly treated either with defibrotide (20) an antithrombotic/profibrinolytic drug or with low-dose subcutaneous heparin [LDSH] (20) for 3 weeks. The efficacy of the two treatments was evaluated by means of computerized thermography monitoring the decrease of the areas at maximum temperature (AMT) and using an analogue scale line to evaluate signs and symptoms. Defibrotide was found to be significantly more effective than LDSH in decreasing both AMT and analogue score after 2 and 3 weeks. By enhancing endogenous fibrinolysis, defibrotide reduced the deposition of fibrin, the ensuing inflammatory response and the production of new thrombi in the affected veins. This was shown by the progressive decrease in the hyperthermic areas. Thanks to its activity defibrotide may be able to promote a faster removal of thrombi and reduce the continuous formation of new thrombi in the inflamed veins. PMID- 2098373 TI - Dopexamine: studies in the general intensive care unit and after liver transplantation. AB - 1. It has been suggested that the use of dopaminergic agents in the critically ill patient may reduce the incidence of renal failure and hence mortality. 2. Dopexamine hydrochloride is a new synthetic catecholamine. Like dopamine, it stimulates dopaminergic receptors. It also stimulates beta 2-adrenoceptors. Unlike dopamine, dopexamine has minimal effect at beta 1-adrenoceptors and no alpha-adrenoceptor activity. 3. Stimulation of renal dopaminergic and beta 2 adrenoceptors independently results in dilation of the renal vasculature. A natriuresis and diuresis is also promoted by dopaminergic stimulation. 4. A comparison between the administration of low dose dopamine and dopexamine in patients undergoing orthotopic liver transplantation resulted in less renal impairment and failure in the dopexamine group, although this did not achieve statistical significance. 5. Dopexamine elimination is reduced in the absence of hepatic function. 6. A patient with terminal liver failure was treated with dopexamine and although oxygen delivery was unchanged, oxygen consumption doubled. This suggests that dopexamine affects other organs as well as the kidneys. PMID- 2098375 TI - A functional role for renal dopaminergic nerves in the dog. AB - 1. Efferent renal nerve stimulation at 5 Hz causes secretion of both dopamine (DA) and noradrenaline (NA) into renal venous plasma. DA comprises about 8% of the total catecholamine overflow; by contrast, DA efflux into femoral venous plasma following stimulation of the lumbar sympathetic nerves is 1% or less of total catecholamine. 2. Intact, but not denervated, kidneys of volume-loaded dogs also secrete both dopamine (DA) and noradrenaline (NA) into renal venous blood at rest, but the DA:NA ratio is considerably higher than that evoked by nerve stimulation. 3. Acute animal treatment with 6-hydroxydopamine (6-OHDA) abolishes stimulus-evoked catecholamine overflow and the usual fall in glomerular filtration and sodium and water excretion that accompanies renal nerve activation. 4. When 6-OHDA is administered in the presence of a selective inhibitor of UptakeDA (GBR 12909), stimulus-evoked DA overflow is selectively protected against the effect of 6-OHDA. Under these circumstances, nerve stimulation increases glomerular filtration and excretion of water, but not of sodium. These effects are abolished by DA1 receptor blockade. 5. These data indicate that DA is released from intrarenal dopaminergic nerve terminals in vivo, both in response to direct nerve stimulation and tonically under conditions of volume expansion. The main effects of dopaminergic nerve activation are juxtaglomerular vasodilatation and inhibition of distal tubular water reabsorption. PMID- 2098374 TI - Regulation of dopamine synthesis in the rat kidney. AB - 1. Both animal and clinical studies clearly suggest a close link between dopamine production and renal delivery of sodium. 2. It appears that tubular transport of sodium and DOPA could represent the rate limiting step for the renal synthesis of dopamine; the membrane transport mechanism is sensitive to the nucleotide cyclic GMP. 3. In sodium overloaded animals AAAD activity appears to be greater than that in controls, but the tubular transport of L-DOPA might be decreased. 4. Since the final product of an increased sodium delivery to the kidney is an increased urinary excretion of dopamine, it might be hypothesized that the outward transport of newly formed dopamine in tubular epithelial cells is also affected by high tubular sodium. PMID- 2098376 TI - Subclassification of peripheral dopamine receptors. AB - 1. There is convincing evidence to suggest that two DA-receptor subtypes exist in the periphery, that can at best be differentiated by the potency of the antagonists SCH 23390 and domperidone: at DA-1 receptors the order of potency is SCH 23390 much greater than domperidone, at DA-2 receptors it is domperidone much greater than SCH 23390. 2. As in the adrenergic, muscarinic or 5-HT-receptor field, future studies employing both molecular biology and pharmacological approaches will show whether such a subclassification is sufficient to explain all peripheral effects of DA or whether DA-1 and DA-2 receptors have to be subdivided into further subtypes. PMID- 2098377 TI - Role of dopaminergic mechanisms in the kidney for the pathogenesis of hypertension. AB - 1. To estimate the role of renal dopaminergic mechanisms in the pathogenesis of hypertension, patients with essential hypertension and animal models of hypertension were investigated. 2. Impaired dopaminergic activity in kidneys for natriuresis was observed in patients with 'salt-sensitive' hypertension and with low-renin hypertension. 3. Decreased dopaminergic activity in kidneys was observed in the Dahl S-rats without salt loading. 4. In spontaneously hypertensive rats, renal dopamine synthesis was enhanced whereas there was a decrease of adenylate cyclase activity in renal tubules. 5. Demonstration of impaired dopaminergic mechanisms in kidneys of human and animal hypertension suggests that renal dopaminergic mechanisms play an important role in development of hypertension. PMID- 2098378 TI - Suppressed dopaminergic activity and water-sodium handling in the kidneys at the prehypertensive stage of essential hypertension. AB - 1. In this study, the question of whether the suppression of the renal dopaminergic system is primary or not was investigated. 2. Renal dopaminergic activity was compared between young healthy normotensive subjects without a family history of hypertension (FH(-] and those with a family history of hypertension (FH(+]. 3. A significant decrease in urinary free dopamine excretion was noted, and the responses of urine volume, urinary sodium excretion, and fractional excretion of sodium to infused dopamine were significantly augmented in FH(+). In addition, a normal level of l-dopa delivery at the renal proximal tubules and a significant reduction in the conversion of l-dopa to dopamine in the kidney were found in FH(+). 4. These findings suggest that renal dopaminergic activity is already suppressed at the prehypertensive stage, and that the reduction in the conversion of l-dopa to dopamine in the proximal tubules may contribute to the attenuation of renal dopaminergic activity in FH(+). PMID- 2098379 TI - Positive identification of victims by comparison of ante-mortem and post-mortem dental radiographs. AB - Radiography of jaws and teeth can provide one of the most reliable sources of information for comparison between ante-mortem and post-mortem conditions leading to definitive evidence in cases of identification. Teeth and dental restorations are resistant to destruction by fire and are therefore very important in identification. The forensic odontologist utilizes dental radiographs taken of the victim before death and compares them to dental data from the remains to assist the identification. Three cases described in this paper illustrate the procedures and techniques of identification using ante-mortem and post-mortem radiographs. PMID- 2098380 TI - Comparison between fingerprint and dental concordant characteristics. AB - Twelve concordant characteristics are used in fingerprint identification. The South African courts of law are prepared to accept 7 concordant characteristics as being "beyond reasonable doubt" in the case of finger, hand and foot prints. In cases of identification by dental means, 12 concordant features have been advocated. In South Africa, with its mixed population in which a large majority have dental formulae containing normal decayed and missing teeth, these patterns show duplication and triplication. It is feasible to submit 7 concordant dental characteristics as positive identification in a mouth containing dental restorations, but in a mouth which features only missing teeth, pattern duplication demands more than 12 concordant characteristics for positive identification. Seven concordant dental characteristics have not been tested in the South African courts to date. PMID- 2098381 TI - Value of the frontal sinus in identification of unknown persons. AB - The reliability of comparing ante- and post-mortem radiographs of the frontal sinus as an identification medium for unknown corpses was tested by means of two radiographs each of 99 individuals. Three independent observers attempted to blind match each pair of radiographs. The results were almost 100% successful and showed that the radiographic image of the frontal sinus, even with varying beam angulation and radiological inexperience of observer is an effective identification medium. PMID- 2098382 TI - Temporomandibular disorders: what to teach in dental school. AB - Temporomandibular joint disorders continue to be a nemesis for health professionals and for patients who are afflicted. The medical/dental student must be taught to recognize this often complex disorder and be able to interact with the various disciplines within the medical/dental profession to provide the care needed. This article discusses problems and a possible approach for establishing continuity of format for classifying TM disorders so students can be taught to recognize them. PMID- 2098383 TI - Timing and character of reciprocal temporomandibular joint sounds in an asymptomatic orthodontic sample. AB - The timing and character of opening and closing temporomandibular joint sounds were evaluated in a sample of 33 asymptomatic subjects with reciprocal clicking. Using stereophonic headphones and videotape recordings, three consecutive reciprocal sounds were recorded and analyzed. The timing of the three consecutive opening and closing sounds was consistent in the majority of subjects, and occurred generally on late opening and middle to late closing. When the timing, character (frequency, amplitude, and duration), and wave patterns were evaluated, a notable amount of variation was observed in the overall sample. This suggested a variety of intra-articular reasons for the reciprocal sounds in this particular sample of subjects. PMID- 2098384 TI - Assessment of patients suffering from chronic orofacial pain of nonspecific origin. AB - The diagnosis and assessment of patients suffering from chronic, persistent orofacial pain of nonspecific origin can be difficult because of the interactions between psychological and somatic signs. Patients with chronic pain are treated differently from those with acute pain and often fail to respond to the usual acute pain model. This article discusses the practical assessment and drug treatment of chronic orofacial pain of nonspecific origin. PMID- 2098385 TI - Radiographic changes in the temporomandibular joint of patients with rheumatoid arthritis, psoriatic, arthritis, and ankylosing spondylitis. AB - Sixty-one subjects with rheumatoid arthritis, 61 with psoriatic arthritis, 61 with ankylosing spondylitis, and 77 healthy controls were examined using orthopantomography to determine the frequency of radiographic changes in the condyle of the temporomandibular joint. Radiographic changes were found significantly more often in subjects with rheumatoid arthritis (66%), psoriatic arthritis (38%), and ankylosing spondylitis (30%) than in controls (12%). Subjects with rheumatoid arthritis also had significantly more radiographic changes, especially cortical erosions and subcortical cysts, than subjects with psoriatic arthritis or ankylosing spondylitis. It may be concluded that rheumatoid arthritis is a more severe disease than psoriatic arthritis or ankylosing arthritis regarding temporomandibular joint involvement. PMID- 2098386 TI - TMD symptomology among denture patients. AB - The relationship between denture wearing and symptoms of temporomandibular disorder (TMD) was assessed with a psychometric test specifically developed to measure TMD symptoms. The subjects were 278 denture patients and 36 elderly patients with a diagnosed TMD. Denture wearers were found to have a higher prevalence of TMD symptoms than the normal population, but the average level of symptoms was of low intensity and not clinically significant. Denture wearers reported fewer TMD symptoms and less stress and psychological distress than TMD patients. Responses to test items assessing perceived malocclusion apparently were not affected by denture wearing. PMID- 2098387 TI - Craniomandibular disorders in patients with different types of headache. AB - One hundred recurrent headache patients, referred for neurologic examination, were randomly invited for a functional examination of their stomatognathic system. The patients were grouped on the basis of headache localization, neurologic diagnosis of the headache, and stomatognathic diagnosis. The relationship between groups was analyzed. Several significant correlations were found between the clinical findings and the localization of headache (P less than 0.05 to P less than 0.001). Patients with or without a definite craniomandibular disorder pain displayed differences in mouth opening capacity (P less than 0.001). The results indicate a close relationship between recurrent headache and craniomandibular disorders, independent of the neurologic diagnosis of the headache. PMID- 2098388 TI - Ankylosing spondylitis associated with temporomandibular joint ankylosis: report of a case. AB - Ankylosing spondylitis is a disease process that causes inflammatory changes of the involved joints. Often the first clinical indication of the condition is lumbosacral pain and discomfort with limited range of motion. Progressive synovial changes eventually involve all of the axial joints including the temporomandibular joint. Although temporomandibular joint dysfunction is usually found in patients with ankylosing spondylitis, there are only nine documented cases of true bony ankylosis. A case report and review of the literature of ankylosis spondylitis associated with true temporomandibular joint bony ankylosis is presented. Surgical treatment included a gap arthroplasty and placement of an interpositional Silastic implant. PMID- 2098389 TI - Clinical significance of bite force reproduction ability. AB - The objective of this study was to evaluate the clinical relevance of measurement of bite force reproduction ability. This parameter was measured at reference force levels of 2, 10, and 50 N in a group of patients with articular and nonarticular temporomandibular disorders and in a control group. The ability to reproduce the reference forces was measured at four equidistant occasions. All subjects poorly and imprecisely reproduced the reference force levels. A trend in the matches or in their imprecision could not be found (P greater than 0.05). Bite force reproduction ability did not differ between the patient group and the control group (P greater than 0.05). It was concluded that measurement of bite force reproduction ability does not provide a useful clinical assessment tool. PMID- 2098390 TI - Distribution and histologic character of osseous concavities in mandibular condyles of young adults. AB - Osseous concavities at the bone--articular soft-tissue interface were identified in 23% of 53 young adult TMJ condyles, with most occurring in the superior sector of the lateral and central aspects. All were filled with articular soft tissue, which provided a smooth articular surface without any evidence of surface breakdown. By extrapolation, radiographic evidence of osseous concavities in this age group should not be interpreted as evidence of articular surface breakdown (arthrosis). The long-term outcome of these concavities cannot be determined from this histologic cross-sectional study. However, the results support initial conservative therapy with monitoring over time. PMID- 2098391 TI - Craniomandibular disorders in an urban Swedish population. AB - A sample of 637 persons was interviewed and examined clinically for signs and symptoms of CMD. Five percent reported daily headaches, and recurrent headaches were more frequently (P less than 0.001) reported by women (28%) than men (15%). Women more often (P greater than 0.001) had headaches upon awaking and in the afternoon. Face, eyes, throat, and neck were the most common locations of pain (20%). Women (18%) more often (P less than 0.05) reported CM symptoms than men (10%), and 16% of the women and 9% of the men considered themselves to be in need of treatment. About 20% reported oral parafunctions (clenching/grinding/biting). The most frequent clinical finding was TMJ sounds (58%). Both clicking and crepitation were more frequent in women (P less than 0.01). Palpation tenderness in the jaw muscles was most frequently found in the lateral pterygoid (34%) and temporal muscle (27%). Women generally had more tenderness and muscles tender to palpation. Mean maximal opening capacity was significantly larger in men. Only 12% of the sample were found to be free of signs of mandibular dysfunction. As signs and symptoms of CMD were common findings, routine dental examination should always include functional examination of the stomatognathic system to evaluate the need of treatment. PMID- 2098392 TI - Distress, jaw habits, and connective tissue laxity as predisposing factors to TMJ sounds in adolescents. AB - Immediately before a craniomandibular examination and measurement of wrist laxity, 96 adolescents answered a questionnaire about jaw habits, jaw activities, symptoms of stress, facial trauma, and TMJ sounds. The sample was divided into five subgroups on the basis of history and stethoscopically detected TMJ sounds. Some groups with TMJ sounds had significantly more jaw habits, jaw activities, and symptoms of stress than the control group (without history and clinically detected TMJ sounds). No significant differences emerged in angular measurement of wrist laxity between groups with TMJ sounds and the control group. This preliminary study indicates that an adolescent's distress may be associated with TMJ sounds. Further studies on subgroups of adolescents with different TMJ related symptoms and signs are urged. PMID- 2098393 TI - Predictive value of the TMJ scale in detecting clinically significant symptoms of temporomandibular disorders. AB - It is important for the dentist to differentiate between subclinical and clinically significant symptoms of TMD. The TMJ Scale tests for clinical significance of pain report, palpation pain, perceived malocclusion, joint dysfunction, and range of motion limitation. To evaluate the accuracy of test results in a patient, the predictive values for each scale must be known. The positive and negative predictive values are calculated and found to produce an increase in diagnostic accuracy of the TMJ Scale compared to pre-test predictions throughout most of the base rate range found in clinical practice. The use of predictive values to interpret test results correctly and to confirm or rule out clinically significant symptoms is described. PMID- 2098394 TI - Prevalence of signs and symptoms of craniomandibular disorders in tinnitus patients. AB - One hundred two tinnitus patients were examined to determine the prevalence of signs and symptoms of CMD. The examination comprised determination of the anamnestic and clinical dysfunction indices according to Helkimo; assessment of the dentition, occlusal factors, and signs of parafunctions; and accomplishment of a tension test. Patients also answered a questionnaire concerning the presence and frequency of CMD symptoms and headaches, as well as influence on tinnitus by mandibular movements, by pressure applied to the TMJ, or by dental therapy. Frequent headaches and fatigue/tenderness in jaw muscles were more prevalent in tinnitus patients than in epidemiologic samples, as was the prevalence of clinical findings of pain on palpation of masticatory muscles, impaired mandibular mobility, and signs of parafunctions. About one-third of the patients reported influence on tinnitus by mandibular movements and/or pressure applied to the TMJs. A theoretic model of causal connections between tinnitus and signs and symptoms of CMD in some tinnitus patients is suggested. PMID- 2098395 TI - Components of complex TM disorders. AB - Temporomandibular disorders are manifested by pain, dysfunction, or both. When chronicity sets in, initial difficulties become aggravated, and a new set of problems may appear. This paper examines these complexities. Special attention is focused on "whiplash" injuries. PMID- 2098396 TI - Clinical signs in patients with disk displacement versus patients with myogenic craniomandibular disorders. AB - Patients with disorders of the masticatory system were clinically examined with reference to tender TMJs and sore muscles of the head and neck, jaw movement range, occlusal interferences, and aberrations of the bite. The 158 patients were divided into three groups according to diagnosis: 46 with reducing disk displacement, 57 with nonreducing disk displacement, and 55 with myogenic CMD. Unilateral symptoms were found in 83% of the two TMJ groups and 47% of the myogenic CMD group. At intraoral palpation, significantly more patients with nonreducing disk displacement displayed tender sites on the symptomatic side. Tender TMJ, crepitation, and restricted condylar translation on the symptom side were significantly more common in the group with nonreducing disk displacement. Mean maximal mouth opening was 31 mm in the nonreducing disk displacement, 42 mm in the reducing disk displacement, and 47 mm in the myogenic CMD group. Total laterotrusion was significantly less in the nonreducing disk displacement group. Myogenic CMD patients had more interferences in retruded position on the symptomatic side and more tender neck and shoulder muscles. Patients with nonreducing disk displacement displayed more signs from the masticatory system than those with myogenic CMD. PMID- 2098397 TI - Craniomandibular asymmetry in headache patients. AB - The stomatognathic system was examined in 100 chronic recurrent headache patients, and the asymmetry in clinical and radiographic findings was studied. A clinically recorded facial asymmetry was found more frequently in patients with a definite CMD pain (P less than 0.001), in patients with mainly a unilateral headache (P less than 0.01), and in patients with a head injury in the history (P less than 0.05). The radiographically determined asymmetry in condylar height in these headache patients was high. More condylar asymmetry was found in migraine patients than in patients with tension headache (P less than 0.05). Asymmetric findings in the hard-tissue condition of the temporomandibular joint were more prevalent in patients with a definite CMD pain and in those with mainly bilateral headaches. PMID- 2098398 TI - Disorders in TMJ research. AB - Epidemiologic studies on TMJ dysfunction etiology often suffer from methodological shortcomings. The problems may partially arise from the fact that the study subject cannot be separated from the "real world" for analyses in the same sense as in classical experimental research. A thorough discussion on the scientific principles in TMJ research is suggested. PMID- 2098399 TI - Differences in headache patients regarding response to treatment of the masticatory system. AB - Twenty-three neurologically examined headache patients completed treatment for a concomitantly diagnosed craniomandibular disorder. More than two-thirds of the subjects responded favorably to the treatment and headaches decreased. Differences between patients regarding the response to treatment were studied. Patients with a decreased headache intensity reported more coexisting neck problems before treatment (P less than 0.05). Patients with an alleviation of headaches showed a larger distance between passive and active maximum mouth opening before treatment (P less than 0.05). The probability of headache improvement by craniomandibular disorder treatment was found to be greater in patients with a difference of 5 mm or more between passive and active maximum mouth opening (P less than 0.05). PMID- 2098400 TI - Animal model for disk displacement. AB - This paper describes the soft-tissue changes associated with surgically created, nonreducing disk displacements in the New Zealand white rabbit. Four rabbits, one control and three experimental, were used. The disk of the control animal had thick posterior and anterior bands separated by a thinner intermediate zone. The disk in the one animal sacrificed immediately after surgical disk displacement was buckled downward at the intermediate zone, with the posterior band lying inferior to the anterior band. The disks in the two animals sacrificed 2 months after surgical disk displacement were grossly deformed and clearly had abnormal internal architecture. Tissue reactions seem to be similar to those observed in human disk displacement specimens, namely disk remodeling and degenerative joint disease. This animal model will aid in the understanding of the progression of this disorder. PMID- 2098401 TI - Prevalence of signs and symptoms of dysfunction in the masticatory system: an epidemiologic study in an adult Swedish population. AB - The prevalence of signs and symptoms of dysfunction in the masticatory system was studied by questionnaire and clinically in a randomly selected age- and sex stratified sample of Swedish adults as a part of an epidemiologic survey on oral health. The prevalence of dental wear was also registered. There were 920 subjects examined, representing a participation rate of 95%. The questions and the clinical examination parameters were in accordance with those suggested by Helkimo in 1973. Reported symptoms decreased with age, while clinical signs increased. The prevalence of severe dysfunction was extremely low. The degree of dental wear increased with age, but extensive wear was extremely rare in women. PMID- 2098402 TI - Relationship between balancing-side occlusal contact patterns and temporomandibular joint sounds in humans: proposition of the concept of balancing side protection. AB - Balancing-side contact patterns and temporomandibular joint sounds were evaluated in 430 young adults. Correlational analysis revealed that there was a highly significant positive correlation between the absence of balancing-side contacts and an increasing prevalence of joint sounds with age (r = 0.975). These data support the hypothesis that certain types of balancing-side contacts may be protective of the temporomandibular joint. PMID- 2098403 TI - Craniomandibular stiffness toward maximum mouth opening in healthy subjects: a clinical and experimental investigation. AB - A new technique for measuring craniomandibular stiffness during mouth opening to the border position was tested. A small force transducer and a jaw tracking device were used to calculate the stiffness in a healthy group of male and female students. Simultaneous EMG recordings were taken from the masticatory muscles to observe the EMG activity during the experimental tests. The craniomandibular stiffness curves of the male group exhibited a stiffer behavior than those of the female group (P less than 0.05). The clinically obtained "endfeel" distance exhibited a significant correlation with different stiffness sections in the stiffness curves (P less than 0.05). Enhanced muscular involvement during mouth opening to the border position was shown as an increase in the clinical endfeel distance. PMID- 2098404 TI - Experiences from a facial pain unit. AB - During the academic year 1988/1989, 282 patients with chronic orofacial pain were referred to the facial pain unit of the University of Helsinki; 143 of these patients were suffering mainly of orofacial dysesthesia and 139 patients of masticatory dysfunction. Thirty-six of the patients with orofacial dysesthesia were referred for a psychiatric consultation. The result revealed a strong mental disturbance component associated with this kind of pain disorder. The patients with orofacial dysesthesia were treated mostly with amitriptyline, clonazepam, and distigmin; the patients with masticatory dysfunction were treated with splints and/or occlusal rehabilitation. PMID- 2098405 TI - Rationale for sequential use of both maxillary and mandibular orthopedic appliances in the treatment of TMJ disorders. AB - This paper describes how the use of a combination of maxillary and mandibular orthopedic appliances by TMJ patients can reduce iatrogenic stress and improve patient compliance with 24-hour use. This combination provides the patient with a proper appliance for anterior repositioning when sleeping and eliminates the fear of iatrogenic tooth depression or movement. PMID- 2098406 TI - [Relative abrasion of toothpastes--a toothpaste for everyone]. AB - Since our last publication in this Journal in February 1988, many new dentifrices have appeared on the market, prompting us to revise our scale of relative abrasion for the most current ones. This relative abrasion scale is determined by weight loss of mechanically brushed specimens (methyl methacrylate) with a slurry from each dentifrice. PMID- 2098407 TI - Healing potential of periodontal osseous defects treated by scaling and root planing. AB - The healing potential of periodontal osseous defects treated by scaling and root planing is demonstrated by the presentation of two clinical cases. PMID- 2098408 TI - Studies on malaria transmission in Orissa state: Part I. Development of a methodology for systematic studies. AB - Standardized collections of Anopheles were conducted by three Entomology Field Investigation Units (FIU's) working in three distinctively different areas of Orissa State. The FIU's conducted identical routine weekly work schedules in each of 12 mesoendemic or hyperendemic study villages every month. In addition, monthly house-to-house fever case surveys were conducted in each study village and biannual malariometric surveys were carried out with the timing being shifted, so that eventually all seasons were included. Such complete, extensive and meticulous entomological and epidemiological data have not been obtained earlier from this area. In fact, until the present longitudinal data became available, it was necessary to rely upon information which was gathered some 40 years ago, when environmental conditions were substantially different. The ensuing article describes the methodology that was employed to establish these systematic studies. PMID- 2098409 TI - Relationship of intestinal parasitism, malaria and under-nutrition to prevalence of anaemia in an urban community. AB - The presence of intestinal parasitic infection, malaria and under-nutrition in relation to prevalence of anaemia was evaluated in a cluster of urban population in Hyderabad. Prevalence of anaemia was 25.7 per cent by clinical assessment from pallor as against 80.5 per cent by estimation of haemoglobin concentration. Presence of intestinal parasitic infection (48.4 per cent) and malaria infection (18.3 per cent) had no statistical significant association with anaemic state. Under-nutrition (31.9 per cent of anaemic individuals) and low per capita monthly income of Rs. 100 and below (60.9 per cent of enaemic individuals) had a statistically significant relationship to anaemia. Clinical assessment of anaemia from pallor had a low sensitivity (31.9 per cent) and a high false negative rate (54.9 per cent), though clinical pallor had a strong statistical association to the presence of anaemia. (p less than 10.01), (Q = 1.0). PMID- 2098410 TI - Kala-azar in Varanasi (UP)--preliminary observations. AB - An epidemiological and entomological survey was conducted in Badohi town of Varanasi district of Uttar Pradesh (India) from where an outbreak of kala-azar was reported. Serological and clinical results showed 83 cases who responded to sodium antimony gluconate. Phlebotomus argentipes and P. papatasi could be detected in area of outbreak. An active transmission of kala-azar is strongly indicated. PMID- 2098411 TI - Seroepidemiological survey of rabies virus antibodies in non-vaccinated dogs in Nsukka Environs, Nigeria. AB - Serum samples from 254 non-vaccinated and apparently healthy dogs of local breeds in Nsukka environs (Nigeria) were examined for the presence of antibodies to rabies virus by haemagglutination-inhibition technique. The prevalence rates of rabies antibodies in less than 3 months, 3-6 months and over 6 months old dogs were 17.5, 7.3 and 22.8 per cent, respectively, and overall 16.1 per cent in the dog population. This is the first documented report of rabies antibodies in non vaccinated dogs in Eastern Nigeria. The results have been discussed with respect to the epidemiology of prototype rabies and rabies-related viruses. It is suggested that the antibodies are most probably due to the non-virulent prototype rabies or rabies-related virus strains. Presence of 83.9 per cent of susceptible dogs in the population suggests mandatory and regular vaccination of all dogs in the interest of public health and control of the disease. The study highlights the need for more studies on epidemiology of rabies and rabies-related viruses in Nigeria. PMID- 2098412 TI - Field evaluation of measles vaccine efficacy in New Seemapuri, Shahdara Zone Delhi during 1990. AB - A field evaluation of measles vaccine efficacy was undertaken in resettlement colonies in New Seemapuri, Shahdara Zone, Delhi, having an estimated population of 20,500 by case-reference method. The standard 30 cluster sampling technique was adopted and 261 measles vaccinated children were matched with 545 measles non vaccinated children. The attack rate of measles was found to be 4.2 and 30.3 per cent in measles vaccinated and non-vaccinated children respectively, which is statistically highly significant (P less than 0.001). The relative risk of developing measles in non-vaccinated child is seven times more as compared to a vaccinated child. Vaccine efficacy (V.E.) evaluated by different epidemiological and laboratory methods was found to be 86.1 per cent +/- 11 at P = 0.05. Further, a large scale study on measles V.E. is recommended in different parts of the country by case-reference method, as it is found to be simple, reproducible and easy to undertake in a field situation. PMID- 2098413 TI - An outbreak of an acute episode of fever with haemoptysis in Andaman Nicobar Islands. PMID- 2098414 TI - Success of integrated methods of control of mosquitoes in India--a review. AB - The integrated methodology for the control of vectors of diseases as well as mosquitoes has become an accepted concept amongst the public health experts. The feasibility of adopting this approach in different situations for mosquito control as per field trials by various institutions has been reviewed in this article. This concept, to some extent, has been in vogue under National Malaria Eradication Programme since long in a practicable way. Satisfactory results have been obtained wherever this approach has been applied carefully. The applicability of the integrated control methodology is not difficult provided various methods to be integrated are chosen and utilized in a rational way. Thorough health education is a prerequisite to awaken the community to accept the methods as part and parcel of routine life. PMID- 2098415 TI - Role of migratory population in keeping up endemicity of malaria in metropolitan cities of India. AB - Urbanisation is rapidly taking place in India. A sizeable number of people migrate to metropolitan cities to take up casual labour jobs and settle in pockets scattered all over the city. They generally pay frequent visits to their native place with a higher malarial endemicity and are believed to be important reservoirs of infection for the native population of metropolis. To investigate this problem, a survey was conducted in 1987-88 to compare the prevalence of chronic malaria in two such pockets of migrant population with that of local population of Delhi from nearby villages. Ninetyone out of 701 (12.84 per cent) immigrants investigated had fever clinically diagnosed as malaria at the time of survey, while in the native population 45 out of 646 (6.97 per cent) had such a history. The difference is statistically significant. Splenomegaly was also significantly higher in migrants (15.41 per cent) than in natives of Delhi villages (3.10 per cent). Migrant population is not covered by active surveillance and live in poor environmental conditions conducive to mosquito breeding and malaria transmission. A special attention needs to be paid to the migratory population in the anti-malaria programme in order to control the transmission of the disease in the cities. PMID- 2098416 TI - Malaria survey in some parts of Namsang Circle of Tirap District, Arunachal Pradesh. AB - A study on malaria conducted in Namsang Circle of Tirap District (Arunachal Pradesh) during April-October 1986 revealed that the malaria incidence due to Plasmodium falciparum was considerably high. RII level of chloroquine resistance was also found among the P. falciparum cases studied by WHo in-vivo test. In entomological survey, Anopheles maculatus was collected more than other 10 anopheline species encountered. A. minimus was detected and incriminated as a vector species. PMID- 2098417 TI - Pattern of relapses in sporozoite induced Plasmodium cynomolgi B infection in rhesus monkeys. AB - The pattern of sequential relapses in 10 rhesus monkeys following inoculation of sporozoites of Plasmodium cynomolgi B has been studied after administering curative dose of chloroquine (5 mg/kg base X 7 days) to eliminate blood parasitaemia after each relapse. Observation for periods ranging from 109 to 245 days showed that the interval between first six relapses was 19.3 +/- 6.77 days (1st relapse), 20.9 +/- 8.43 days (2nd relapse), 22.8 +/- 8.55 days (3rd relapse), 27.8 +/- 10.0 days (4th relapse), 31.67 +/- 11.50 days (5th relapse) and 32.5 +/- 16.26 days (6th relapse). The results of this study indicate a gradual extension of the relapse interval in successive relapses. PMID- 2098418 TI - Epidemiological profile of outbreaks of cholera in India during 1975-1989. AB - Cholera has been present in India since antiquity. Six pandemics originated in Indian subcontinent. The present seventh pandemic caused by El Tor Vibrio cholerae started from Indonesia (Sulawesi) in 1961 and entered India in 1964. By the end of 1965 it has replaced the age old classical V. cholerae. Many of the States which never had cholera or were free from it for a long time got infected and became endemic foci of El Tor infection. This article reviews the epidemiological features of important outbreaks reported after 1975 in India. PMID- 2098419 TI - Prevalence of high risk children under five--a study in rural Delhi. AB - 678 under five children were surveyed in village Shahbad Mohammadpur, Delhi. Two weeks morbidity was also recorded. 47.9 per cent children had one or more risk factors studied. Significantly more female children (54.1 per cent) were at risk than male children (43.3 per cent). 433 risk factors were observed in 325 at risk children. Majority of them had one or two risk factors. Birth interval less than two years and malnutrition were most frequent risk factors. At risk children suffered significantly more than not at risk (21.2 per cent vs 14.4 per cent). The results confirmed the validity of the risk factors considered for the study. PMID- 2098420 TI - Sero-epidemiology of measles--a three years prospective study in a rural population of Rajasthan. AB - A community based prospective study on measles was undertaken during 1986 to 1988 in Ramgarh village of Alwar district (Rajasthan) to elucidate epidemiological features of measles. The initial population of the village was 5258 with 2018 children (0-14 years) which rose to total population of 5923 with 2200 children in 1988. During the entire period of study, all the children (0-14 years) were covered regularly through monthly domicilliary visits by trained paramedical personnel under direct supervision of Medical Officers. A total of 208 measles cases were detected which gave an overall incidence rate of 31.5 per 1000 children (0-14 years) per year. Incidence rate was highest in children of 2-5 years of age group and lowest (4.6 per 1000) in 10-14 years of age group. The maximum number (86.5 per cent) of cases occurred during the first six months of year. The Kolmogrov-Smirnov statistical method validated the seasonal character of the disease (Vn = 5.36, p less than 0.01). A significant (P less than 0.005) rise in seropositivity with increase in age was observed in children (6-36 months) who had no previous history of measles and measles immunization during their life time. A higher rate of sero-conversion was observed in children vaccinated after 10-months of age than those before. No significant relationship of seroconversion following vaccination could be seen with age of vaccination (p greater than 0.50), sex and nutritional status (p greater than 0.10). PMID- 2098421 TI - Incidence of australia antigen (HBs Ag) in Himachal Pradesh. AB - 2405 high risk subjects (1193 patients attending STD clinics, 1012 blood donors and 200 hospital personnel) and 500 apparently healthy individuals representing all the twelve districts of the State of Himachal Pradesh were screened for HBs Ag employing reverse passive haemagglutination (RPHA) technique. HBs Ag positivity was found to be 6.77 per cent in test groups and 3.6 per cent in the control group. Maximum positivity was found in STD patients (9.55 per cent) followed by hospital personnel (8 per cent) and blood donors (3.26 per cent). The highest incidence was noticed in district Kullu and no positive case was found in Lahaul and Spiti district of Himachal Pradesh. Remedial measures for prevention of Hepatitis-B virus infection have been emphasized. PMID- 2098423 TI - Present status of Plasmodium malariae infection in Bastar District (M.P.). AB - Plasmodium malariae infection was detected in Bastar district (M.P.) during malaria survey in 1981-83. The data collected during the survey was compared with the earlier records of P. malariae infection in the area. From the data it can be seen that the infection in this area has declined due to the ecological/developmental activities undertaken by Government. All the cases were found to be indigenous and approximately 62 per cent infection was found in age group of 10-14 years irrespective of sex. More than 60 per cent of P. malariae infections were positive for gametocytes. Three day regimen of 4-aminoquilines for the treatment was found quite effective. PMID- 2098422 TI - Efficacy of sulfalene and pyrimethamine combination drugs alone and with quinine in treatment of P. falciparum cases in chloroquine resistant areas of north east India. AB - Studies were carried out in some areas of Assam, Nagaland, West Bengal and Mizoram where chloroquine resistant strains of Plasmodium falciparum were present during 1983 and 1984, to see the efficacy of treatment of P. falciparum cases with SLP alone or with quinine sulphate. The findings have indicated that SLP in the dosage of sulfalene (1000 mg) + Pyrimethamine (50 mg) is suitable for treatment of P. falciparum cases not responding to chloroquine therapy in N.E. India. Treatment with sulfalene (1500 mg) + Pyrimethamine (75 mg) has no advantage over the SLP (1000 + 50) mg. Combination of quinine (1000 mg x 3 days) + SLP (1000 + 50) mg is better with 100 per cent cure rate. In Karhi Anglong district (Manja PHC) of Assam response to these drug combination is however less. PMID- 2098424 TI - Studies on malaria transmission in Orissa State, India 1981 through 1986. II: Observations on the Anopheles fauna. AB - A general presentation is made of data derived from systematic trend studies on the Anopheles fauna in 12 study villages of Orissa State, India. Adult and larval species prevalences, seasonal densities of prominent anophelines and predilections of various species to feed on human blood are discussed and demonstrated. PMID- 2098425 TI - Growth study of a nonpathogenic strain of Leishmania donovani with different nutrients. AB - The studies on growth pattern of a nonpathogenic Leishmania donovani, strain UR6, in different media showed that it can be regularly cultivated amd maintained in modified Ray's Medium (Agar) and three other liquid media, namely DME Medium, Medium 199 and RPMI-1640 which are manufactured in India. The well known N.N.N. Medium provided quantitatively poorer growth in comparison to these medium. Measurement of L. donovani cell concentration by optical density in a spectrophotometer has been worked out for expressing immunochemical observations on antigens in terms of cells per mililitre. PMID- 2098426 TI - Prevalence of toxoplasma antibodies among women with BOH and general population in Delhi. AB - One thousand and thirty-six serum samples obtained from women with bad obstetric history (BOH) were subjected to detection of toxoplasma antibody by indirect immunofluorescent antibody test (IFAT) using whole promastigotes of Rh strain of Toxoplasma gondii as antigen. Thirtyone (2.99 per cent) samples were found to be positive (titre greater than or equal to 1:64). Of these 31 patients' sera 27 (87.09 per cent) showed rising titre of antibody when second samples were drawn after 4 weeks. Two hundred serum samples from general population were also assayed and only 2 (1 per cent) were found to be having toxoplasma antibodies in titre of 1:64. The observations suggest low prevalence of toxoplasmosis in and around Delhi which is in consonance with the food habits of local people and their infrequent contact/association with cats. PMID- 2098427 TI - Zoonoses in India. AB - Intimate and prolong contact between man and animal facilitates the transmission of various communicable diseases between them. These diseases (zoonoses) are more prevalent in developing countries especially in the rural areas. These diseases virtually stunt the economic and social growth also. Lack of authentic data and awareness regarding the occurrence of these diseases and their true impact on public health have acted as major obstacles in instituting adequate and effective control measures. The information available regarding the current status of few important zoonoses in India is being presented in this paper. PMID- 2098428 TI - A study of two-weekly incidence of ARI in under-five children of rural area of Alwar (Rajasthan). AB - A retrospective study of two-weekly incidence of acute respiratory infections (ARI) in the under-five children of rural area of Alwar District (Rajasthan) based on the previous fourteen days' recall by the mothers was undertaken during December 1989 to assess the magnitude of the problem and its' risk factors. The two-weekly ARI incidence was reported to be 33 episodes per 100 under-fives. Mothers in higher socio-economic strata reported higher incidence of ARI for their children due to more accurate recall. Majority of ARI cases (76 per cent) were found to be of mild degree. 26 per cent of deaths in under-fives during the previous year were reported to be ARI-related. 50 per cent of ARI cases were left untreated. Among the treated group, private practitioners were found to be the main source of health care. PMID- 2098429 TI - Patterns of erythropoiesis and anaemia in malaria. AB - Of 138 patients with malaria, 90 were found to be having Plasmodium falciparum in their peripheral blood smears. Megaloblastosis alone or in combination with the other patterns of erythropoiesis was observed in 82.1 percent cases of chronic P. falciparum malaria as compared to 36.3 and 26.5 per cent cases of acute P. falciparum and P. vivax malaria respectively. Iron deficiency was observed in 15.5 percent cases of chronic P. falciparum, 18.2 per cent cases of acute P. falciparum and 13.3 per cent patients of P. vivax infection. Of patients with chronic falciparum malaria, 33.3 percent revealed features of both megaloblastosis and defective iron utilization and transient hypoplasia of marrow was observed in 8.9 per cent of these cases. PMID- 2098430 TI - Primaquine: its effect on cellular immune response of normal rhesus monkeys. AB - The effect of primaquine on the cellular immune responses (lymphocyte subpopulations and their proliferative responses with PHA, Con-A and LPS, and phagocytosis by monocytes) of normal rhesus monkeys was studied under both in vivo and in-vitro conditions. When the lymphocytes and monocytes from normal animals were treated in-vitro with primaquine, at concentration normally attainable during therapy, a significant inhibition in blastogenic response of lymphocytes and phagocytic capacity of monocytes was noticed after 4 hours of treatment. In contrast, the in-vivo effect of primaquine treatment on these cells was innocuous. From this study it is clear that the primaquine does not act as an immunosuppresant and can be given safely to any type of malaria patient. PMID- 2098431 TI - An in-vitro profile of the action of four antimalarials on indigenous cases of Plasmodium falciparum malaria in Karnataka. AB - In view of the emergence of chloroquine resistant Plasmodium falciparum from more and more geographical areas profiling of the responses to other available antimalarials by in vitro methods have become essential. A preliminary study undertaken in two Primary Health Centres of Karnataka State, India show the presence of strains of P. falciparum resistant to chloroquine and amodiaquine. The response for amodiaquine was poor as compared to chloroquine. The isolates were, however, sensitive to mefloquine and quinine. PMID- 2098432 TI - Serogroups of beta-haemolytic streptococci isolated from clinical specimens in parts of eastern Nigeria. AB - From 470 patients, mainly of respiratory infection, attending University of Nigeria Teaching Hospital, Enugu, Nigeria 212 (45 per cent) strains of beta haemolytic streptococci were isolated and 25 per cent of the isolates belonged to Group B Streptococcus. Percentage isolation of other groups was A(21.2), G(20.3), C(16.1), D(10.8) and F(5.2). Maximum (11.2 per cent) isolates were from age group of 5-17 years. All serogroups were sensitive to penicillin G and ampicillin despite the prevalent misuse of drugs in the state and the country at large. PMID- 2098433 TI - Non-specific vaginitis vis-a-vis Gardnerella vaginalis. AB - One hundred patients of vaginitis along with 50 age matched control women were studied. Non-specific vaginitis (NSV) was diagnosed on the basis of the presence of at least any three of the four parameters which included presence of thin gray homogeneous discharge, pH of the discharge greater than or equal to 4.5, liberation of fishy odour from the discharge after adding 10 per cent KOH and presence of clue cells Using these criteria, NSV was diagnosed in 22 of the 100 patients and in 4 of 50 control women. Gardnerella vaginalis was cultured from 23 of the 26 women with NSV and 19 women without NSV (8 patients and 11 normal women). Women with NSV showed statistically significant difference in the presence of clue cells, amine test positivity and concentration of G. vaginalis as compared to women without NSV. PMID- 2098434 TI - The effect of age and sex on incidence of kala-azar. AB - Of 89 persons suspected to be suffering from kala-azar, the parasite could be demonstrated in 54 of them by smear and culture examination of the bone marrow aspirates. In the pre-pubertal age group (4-12 years), incidence of kala-azar in both the sexes was practically the same (P greater than 0.05). However, in the reproductive age-group (males 13-60 years, females 12-45 years), there were significantly less cases in females than males (P less than 0.05). This protection could be due to the presence of female sex hormones. The incidence of kala azar in females was 83.3 per cent in pre-pubertal age group, while in the reproductive age group, it was 35.5 per cent. The difference is statistically highly significant (P less than 0.01). PMID- 2098435 TI - Seroimmunity to rubella virus infection in young adult females in Delhi. PMID- 2098436 TI - Antibodies to human T-cell leukemia virus type 1 in patients with malignancies in the Gizan area of Saudi Arabia. PMID- 2098437 TI - Salmonella mgulani (38:i:1,2) isolated for first time in India. PMID- 2098438 TI - Rural community perception and prevention practice towards filariasis in East Godavari District of Andhra Pradesh. PMID- 2098439 TI - Eruptive changes in the axial inclination of lower incisor teeth--a longitudinal study. AB - A longitudinal cephalometric study investigated the change in lower incisor inclination in a group of 32 subjects over a period from 5-10 years of age, with yearly cephalometric radiographs and 6 monthly study models. In a previous study, it was shown that in all of these subjects, the lower incisors became more proclined over this 5 year period. Changes in the rate of proclination of the lower incisors over this period were studied, and this was related to events such as eruption, and contact with the upper incisors or palatal mucosa where this occurred. The association between the inclination of lower incisors before and just after eruption, and their "final" inclination was investigated, and the possible explanations and implications of the findings are discussed. PMID- 2098440 TI - Relationship between attitudes, behaviour and levels of dental caries among 15 year-old Saudi Arabian and Irish children. AB - In 1987, the first major dental epidemiological study was carried out in the Kingdom of Saudi Arabia, with the help and cooperation of the WHO Collaborating Centre for Oral Health Services Research, University Dental School, Cork, Ireland. As part of the project, the 15-year-old age group underwent an interview survey in order to ascertain if oral health attitudes and behaviour were related to oral health outcomes, as measured by the mean DMFT for the group. In common with the findings of similar studies in other countries, including Ireland, little or no correlation between the sociological variables and oral health outcomes was apparent. Such findings, however, simply highlight the unreliability of cross-sectional designs when attempting to isolate a relationship between a cumulative condition, such as dental caries, and parameters which clearly change with time. The differences found in the oral health behaviour of the Saudi Arabian and Irish 15-year-old children is particularly noticeable in respect of the frequency of intake of sweet foods and drinks. PMID- 2098441 TI - Sensory morbidity after palatal flap surgery--fact or fiction? AB - Retrospectively, a study was undertaken as to how dividing the nasopalatine nerve (whilst raising a palatal flap) effects postoperative sensory morbidity. 85 patients were separated into two groups: (a) nasopalatine nerve sectioned during surgery (45), and (b) nerve left intact (40). A clinician, blind to the patient's group, used indirect questioning, direct questioning, and examination to assess if the patient was aware of any deficit or if one existed of which he/she was unaware. The results showed that none of the patients in either group were aware of altered sensation in their palate post-operatively--two patients in the incised group experienced a temporary numbness. Examination revealed that five patients in the nerve divided group had a small area of altered sensation but this was not significant either for the patient or statistically between the groups. Conclusion--there is no significant sensory morbidity if the naso palatine bundle is sectioned during palatal flap surgery. PMID- 2098442 TI - Dento-facial injuries. The need for comprehensive reporting. PMID- 2098443 TI - Early orthodontic screening. AB - Preventive and interceptive orthodontics encourages inappropriate expectations from treatment. It implies that if the right treatment is done at the early age, no further treatment would be needed. This is obviously not true but assessment and/or treatment in the mixed dentition can be very helpful in many cases. This paper discusses some of the indications for early assessment/treatment. PMID- 2098444 TI - A.I.D.S.--a review: its relationship to dentistry. PMID- 2098445 TI - Leeuwenhoek and the structure of dentine. AB - This short paper includes extracts from the original translations of Leeuwenhoek's descriptions of the histology of teeth, investigates his findings and demonstrates that in addition to describing dentinal tubules, he may have identified the presence of calcospherites within that tissue. PMID- 2098446 TI - Characteristics of dental students in Ontario and Northern Ireland. AB - The aim of the study was to investigate whether differences existed between the behaviour and attitudes of dental students in London, Ontario, and Belfast, Northern Ireland. While there was no difference in the frequency of brushing in the two groups, a higher proportion of the Canadian students practised interdental cleaning. One surprising result was the difference between the two groups regarding the methods of caries prevention which they would recommend for children. PMID- 2098447 TI - Congenital absence of permanent teeth among Irish school-children. AB - The Orthodontic records of 3,056 patients attending a Regional Orthodontic Unit were examined, to assess the prevalence of hypodontia. Orthopantomogram radiographs were available for all patients. The congenital absence of third molars was not considered. The prevalence of hypodontia was 11.3% which was high in comparison with previous studies. However it was in keeping with more recent studies from the U.K. and Ireland. PMID- 2098448 TI - Oral cancer mortality in the Republic of Ireland 1979 to 1986. AB - A descriptive study of Oral Cancer Mortality in the Republic of Ireland is presented. The aim was to collate the data on oral cancer deaths (ICD9 140-146, 149) from the Department of Health Reports on Vital Statistics for the years 1979 86 and determine the numbers, sex distribution and rates. The annual number of oral cancer deaths represented a very small proportion of cancer deaths and all deaths. Deaths due to neoplasms of the tongue were the most common. Males had greater oral cancer death rates than females; death rates increased with age; two thirds of the deaths occurred over the age of 64 years. Age adjusted oral cancer death rates showed no significant change in male or female rates between 1979 and 1986. PMID- 2098449 TI - Regional variations in dental caries levels in Irish children. PMID- 2098450 TI - Who seeks surgical-orthodontic treatment? AB - Clinical examination records of more than 1000 patients evaluated in the Dentofacial Clinic at the University of North Carolina were reviewed to determine whether patients with certain characteristics were more likely to seek and to receive surgical treatment. Facial asymmetry was found in 25% of the patients. Women were twice as likely as men to seek evaluation and were more likely to receive surgical treatment once evaluated. Individuals with a long face or skeletal Class III problem appeared more likely to seek evaluation than did those with mandibular deficiency and normal or short facial height, but the decision to accept or reject a recommendation for surgery did not seem to be related to morphologic characteristics. PMID- 2098451 TI - Condylar position control during maxillary surgery: the condylar positioning appliance and three-dimensional double splint method. AB - A new method for positioning the maxilla and condyle after Le Fort I osteotomy maintains the patient's vertical dimension (ie, the relation of the mandible to the skull above the osteotomy plane) in the preoperative and postoperative positions during both cast surgery and actual surgery. During surgery the condylar positioning appliance is fixed to the anterolateral zygoma and the lateral cortex of the mandibular ramus bilaterally to orient the mandible in centric relation. The condylar positioning appliance is used with the three dimensional double splint method. Two prefabricated splints enable three dimensional positioning of the maxilla in the fixed mandibular position during surgery. Postoperatively, the mandible can be rotated into the new centric occlusion. PMID- 2098452 TI - Intraoperative recording of trigeminal evoked potentials during orthognathic surgery. AB - The inferior alveolar branch of the trigeminal nerve is at risk during sagittal split osteotomies, a common maxillofacial surgical procedure. The purpose of this study was to evaluate the use of somatosensory evoked potentials to assess the functional state of the nerve during surgery. Ten patients scheduled for bilateral sagittal split osteotomies were studied. Recording electrodes were placed on the scalp overlying vertex and inion, and subcutaneous stimulating electrodes were inserted 1 cm apart over the mental foramina. Recordings were made bilaterally from all patients. Baseline recordings were made after anesthetic induction, prior to the initial incision. Subsequent recordings were made just prior to the mandibular bone cuts, during splitting of the mandible, and after rigid fixation of the mandible. Analysis of the baseline data identified a series of peaks at 20 and 26 milliseconds following stimulation. This biphasic response was consistent across subjects and was chosen for subsequent analysis. Both the amplitude and latency of the response were significantly (P less than .05) affected when the nerve was retracted medially while the medial horizontal bone cuts were made. However, in all patients, the waveforms returned to baseline values within 10 to 20 minutes. No consistent changes were found in the evoked potentials recorded at other times during the surgical procedure. The results indicate that surgical retraction can cause a transient neurapraxia, but they do not account for postsurgical loss of sensation, which could be due to other factors, such as edema and swelling. PMID- 2098453 TI - Comparison of relapse in bilateral sagittal split osteotomies for mandibular advancement: rigid internal fixation (screws) versus inferior border wiring with anterior skeletal fixation. AB - A retrospective study of 28 patients treated by bilateral sagittal split ramus osteotomies for mandibular advancement and stabilized by two different methods of fixation was performed. Fourteen patients received rigid fixation, and 14 patients had inferior border wiring with anterior skeletal fixation. The postoperative and long-term cephalograms (greater than 6 months) were analyzed in a horizontal and vertical direction for relapse. In the horizontal direction, the rigid group experienced a 1.5% relapse in point B and a 3.2% relapse in pogonion. In the vertical direction, the rigid group experienced a 4% relapse in point B and a 9% relapse in pogonion, while the wire osteosynthesis group had a 13% relapse in point B and a 6% relapse in pogonion. These results support the belief that rigid fixation is more stable than is wire osteosynthesis and that it helps prevent relapse in the long-term results. PMID- 2098455 TI - Evaluation of soft tissue profile following intraoral ramus osteotomy in Chinese adults with mandibular prognathism. AB - Twenty-five Chinese adults with mandibular prognathism were treated with either the intraoral vertical subcondylar osteotomy or the bilateral sagittal split ramus osteotomy. The patients were kept in maxillomandibular fixation for 6 to 8 weeks while osteosynthesis was achieved with the use of intraosseous wiring. Serial lateral cephalograms were taken presurgery and between 12 and 26 months postsurgery, and specific soft and hard tissue points were digitized on a computer. The mean mandibular setback postsurgically was 8.4 +/- 3.2 mm, with a 5.2-degree reduction in point A-nasion-point B angle. Posterior movement of pogonion, point B and the mandibular incisal edge was accompanied by posterior movement of 95% at soft tissue pogonion (r = .96), 89% at soft tissue point B (r = .83), and 67% at labrale inferius (r = .81), respectively. The correlation between changes in the labrale superius and mandibular setback appeared to be dependent on both the amount of mandibular setback and the degree of mandibular rotation during the setback surgery. The presently reported ratios of the soft tissue response to hard tissue movement vary from those reported in white patients by other researchers, which confirms the need for different ratios for different racial types. PMID- 2098454 TI - Closed-intraoral wound suction: a prospective analysis of 65 cases and a review of the literature. AB - Minimizing postsurgical swelling, edema, and pain are important to the patient because of the elective nature of orthognathic surgical procedures. Closed intraoral wound suction was placed following mandibular osteotomies in 65 consecutive patients. The volume of drainage ranged from 35 to 285 mL (mean of 113 mL). The use of closed-intraoral wound suction only minimally increased the incidence of postsurgical infection and at the same time resulted in considerable subjective improvement in postoperative facial appearance and a decrease in tissue edema and pain. PMID- 2098456 TI - Craniographic examination of the condylar angle and the maxillary incisal palatal angle in Bedouin skulls. AB - Craniographic registrations were used to examine 25 Bedouin skulls. The skulls were divided into three groups according to the anatomy and position of the maxillary incisor. Correlations between condylar guidance angle, maxillary incisal palatal angle, attrition, and flaring were investigated. No correlation was found between the condylar and maxillary incisal palatal angles. In the presence of severe attrition and/or flaring, the maxillary incisal palatal angle was reduced and mild reduction was also found in the condylar guidance angle. A strong correlation was found between the level of attrition and flaring. PMID- 2098457 TI - Periapical surgery in a Norwegian county hospital: follow-up findings of 477 teeth. AB - Four-hundred seventy-seven teeth treated by periapical surgery by one surgeon were followed up until a stable radiographic situation was recorded. Radiographic findings were classified into one of four groups: 1, complete healing; 2, incomplete healing (scar tissue); 3, uncertain healing; or 4, unsatisfactory healing. Evaluation was performed independently by an endodontist and the oral surgeon and cases of disagreement were subjected to joint evaluation. Difficult cases and borderline cases were judged by an oral radiologist. Complete healing was observed for 78% and incomplete healings (scar tissue) for 9% of the teeth. The size of the latter group was strongly influenced by the number of cases with large preoperative lesions. When the material was grouped as "success" (complete healing, scar tissue healing) and "failure" (uncertain healing, unsatisfactory healing), a 13% failure frequency was recorded. Twenty-eight percent of the cases treated with retrograde fills failed compared with 4% in the orthograde group. PMID- 2098458 TI - High precision, simulated cutting efficiency measurement of endodontic root canal instruments: influence of file configuration and lubrication. AB - A high precision method is presented for measurement of root canal instrument cutting efficiency in pure, linear movements. Operator-independent instrumentation is achieved by means of an automatic, mechanical test rig mounted as an accessory in an Instron tensile testing machine. It is now possible to do reliable cutting simulation that closely represents clinical motions. Cutting efficiency is assessed via "wear" volume measurement by means of three dimensional surface mapping on bovine bone serving as a dentin substitute. A volume precision of 3 x 10(-3) mm3 is achieved which is equivalent to a weight resolution better than 10 micrograms. In particular, cutting efficiency data for K-type and H-type files is presented showing an enhanced performance (by roughly a factor of 3) in the latter case. Lubrication is also shown to increase the cutting efficiency (+200% for the K file and +30% for the H file). Water and 2.5% sodium hypochlorite solutions have equivalent effects. PMID- 2098459 TI - Comparison of the sealing ability of four obturation techniques. AB - This study compared the apical seal produced by four obturation techniques. The Canal Finder system was compared with lateral condensation, the Ultrafil system, and the sectional warm gutta-percha techniques. Forty-two anterior single-rooted teeth were instrumented. Ten teeth were not obturated and served as positive and negative controls. The apical seal was tested for leakage with 0.25% methylene blue dye. The teeth were shaved horizontally and dye penetration was measured with a Boley gauge. Results revealed there was no statistically significant difference among the four obturation techniques. PMID- 2098460 TI - In vitro cytotoxicity of root canal filling materials: 1. Gutta-percha. AB - Gutta-percha (GP) has been the most widely used root canal filling material because of its well-known low toxicity. The inertness of GP, however, was challenged recently. The purpose of this study was to evaluate the toxicity of marketed endodontic GP using the radiochromium release test. Fourteen commercially available and three experimental GP brands were tested. Raw GP, zinc oxide, and barium sulfate, which were considered major components of GP points, and zinc ions were also evaluated. The material was spread to cover the bottom of testing wells after being dissolved in chloroform or warmed. A labeled suspension of L929 cells was added to the wells. After incubation at 37 degrees C for 4 and 24 h, extracellular radiochromium in the culture medium was measured and calculated in percentage of the total intracellular label. Spontaneous release of radiochromium was used as control and the results were considered to be within normal limits either at 4 or 24 h. All chloroform-dissolved GP showed low toxicity at 4 h, whereas warmed GP showed statistically significant differences at 4 h. Both dissolved and warmed GP were toxic at 24 h. The raw materials and barium sulfate were not toxic, whereas zinc oxide and zinc ions showed marked toxicity. All GP points tested were toxic at longer observation periods, and the toxicity was attributed to leakage of zinc ions into the fluids. PMID- 2098461 TI - Embryotoxicity and teratogenicity of formocresol on developing chick embryos. AB - White Leghorn chick embryos were used to investigate the embryotoxicity and teratogenicity of 25 and 50% Buckley's formocresol. Embryos were injected at 48 h and sacrificed on the ninth day of incubation. The percentage of mortality of sham and vehicle controls was 4.8 and 17.7%, respectively, whereas eggs injected with 25 and 50% formocresol displayed a 40 and 100% mortality rate. Gross morphological abnormalities, weights, and crown-rump lengths were determined, demonstrating that Buckley's formocresol is embryotoxic and teratogenic in chick embryos. Gross morphological changes were noted to include cranial hematomas, facial abnormalities, eye and beak deformities as well as alterations in feather germ appearance. Histological changes included alterations in the organization of the eyes, and formation of the beak, palate, vasculature, musculature, cartilage, and bone. Moreover, experimental embryos displayed a retardation of development in that they lagged behind their controls by approximately 24 to 36 h. PMID- 2098462 TI - Physical dimensions and torsional properties of rotary endodontic instruments. 1. Gates Glidden drills. AB - A laboratory study was performed on Gates Glidden drills to determine their physical dimensions and torsional properties. Five samples of sizes #1 to #6 drills from two brands distributed in the United States were measured for physical dimensions. Five samples of the most commonly used sizes #1, #2, and #3 drills from these two brands were tested at failure in both the clockwise and counterclockwise directions using an analog torque meter. The values for the bur head dimensions of both brands correspond closely to those established by the ISO. The mean values for torque at failure for both the clockwise and counterclockwise directions showed no statistically significant difference for each brand-size combination. However, some instrument groups had separation or fracture sites near the bur head, while other groups underwent failure near the hand-piece end. This study is the first part of a continuing investigation to establish standards for rotary endodontic instruments. PMID- 2098464 TI - Clinical evaluation of five electronic root canal length measuring instruments. AB - A previous in vitro study has shown high accuracy, but no clinically significant differences in a group of five electronic root canal length measuring instruments. The purpose of this study was to evaluate and compare the performance of the same group of instruments under clinical conditions and to correlate their accuracy to radiographic estimates of canal length. Five electronic root canal length measuring instruments were used to measure the working length to the "apex" in 20 single-rooted teeth scheduled for extraction. After extraction, the actual canal length was measured visually to a point just within the apical foramen. This length was compared with instrument length as determined electronically. The accuracy of the instruments in determining canal measurement within +/- 0.5 mm from the apical foramen varied from 55 to 75%. The differences between the instruments were not statistically significant. On average, all of the instruments except for the Endocater gave canal length measurements that were beyond the apical foramen. The variability of the measurements, which was comparable to that of estimates of canal length from preoperative radiographs, indicated that radiographic verification of the working length is still desirable. PMID- 2098463 TI - Dentin permeability: effects of endodontic procedures on root slabs. AB - The permeability of human radicular dentin was measured as a hydraulic conductance before and after treatment with K files and before and after subsequent treatment of the endodontic smear layer with NaOCl, 50% citric acid, or 3% monopotassium-monohydrogen oxalate. Filing reduced dentin permeability 25 to 49%, respectively, depending upon whether outer or inner root dentin was filed. The permeability of these smear layers was unaffected by 5% NaOCl but increased many times after treatment with 50% citric acid for 2 min. Oxalate treatment lowered root dentin permeability to levels below that produced by creation of smear layers due to the production of a crystalline precipitate. PMID- 2098465 TI - Apical surgery on a two-rooted maxillary central incisor. AB - This article presents a case of a two-rooted maxillary central incisor with previous endodontic therapy. One root canal was well filled and the other partially filled. A post was present in each root and the tooth had a crown. Surgery was performed and an amalgam retrograde filling was placed. A 6-month postoperative radiograph shows repair. PMID- 2098466 TI - Indoor resting heights of some anophelines in Colombia. AB - The nocturnal, indoor resting behavior of female anophelines in Colombia was studied. Anopheles darlingi and An. marajoara had a tendency to rest close to the ground, but An. oswaldoi and An. rangeli rested higher up. This behavior was independent of bloodfed status (except for An. oswaldoi) and whether the surface had been sprayed with DDT. With this information it should be possible to modify insecticide applications to coincide with the resting preferences of these species. PMID- 2098467 TI - Limnological and botanical characterization of larval habitats for two primary malarial vectors, Anopheles albimanus and Anopheles pseudopunctipennis, in coastal areas of Chiapas State, Mexico. AB - Field surveys of mosquito breeding sites on the Pacific coastal plain and foothill regions of southern Chiapas, Mexico, were carried out in the dry and wet seasons of 1988. At each site, selected environmental variables were measured or estimated, presence and percent cover of aquatic plants recorded, a water sample collected for subsequent analyses, and 10-30 dips made for mosquito larvae. Logistic regression and discriminant analyses revealed that the occurrence of Anopheles albimanus larvae in both the wet and dry seasons was positively associated with planktonic algae and negatively associated with altitude. In the dry season, An. albimanus larvae were largely restricted to the margins of permanent water bodies and were associated with the presence of floating plants, particularly Eichhornia crassipes. During the wet season An. albimanus larvae were positively associated with emergent plants, particularly seasonally flooded Cyperaceae, and phosphorus (PO4) concentrations, and were negatively associated with abundant filamentous algae, high levels of total suspended solids (TSS) and Salvinia. In the dry season, An. pseudopunctipennis larvae were positively associated with filamentous algae, altitude and the presence of Heteranthera if encountered in a riverine setting, and were negatively associated with water depth. During the wet season, flooding eliminated typical flood plain An. pseudopunctipennis habitats, and larvae were rarely encountered. PMID- 2098468 TI - Genetic analysis of rock hole and domestic Aedes aegypti on the Caribbean island of Anguilla. AB - Genetic variation was characterized at 11 enzyme coding loci in Aedes aegypti collected from 3 rock hole and 4 domestic sites on the island of Anguilla, West Indies. The pattern of gene frequency variation suggests that these mosquito samples do not constitute a single panmictic population, but there are no large consistent differences between rock hole and domestic forms to parallel the East African sylvan-domestic dichotomy. With the exception of one of the domestic populations, two loci did however show some gene frequency differences consistent with genetic differentiation between the 2 habitat types. We conclude that whereas there may be some degree of differentiation between the 2 habitat types, local eradication attempts and sporadic gene flow cause temporal and spatial volatility that is sufficient to swamp these differences. PMID- 2098469 TI - Effect of indoor residual spraying of DDT and bendiocarb on the feeding patterns of Anopheles pseudopunctipennis in Mexico. AB - Intense and persistent use of DDT for malaria control has increased resistance and induced exophilic behavior of Anopheles pseudopunctipennis. An evaluation of bendiocarb and DDT to control this species in Sinaloa, Mexico, showed that, in spite of DDT-resistance, both insecticides produced similar effects. Feeding patterns were analyzed to explain these results. Resting mosquitoes were collected over the dry and wet seasons. Anophelines were tested in an ELISA to determine the source of the meals. The human blood index (HBI) ranged from 3.3 to 6.8% in DDT- and from 12.7 to 26.9% in bendiocarb-sprayed houses. Irritability and repellency in DDT-sprayed houses could explain the reduced HBI. In contrast, bendiocarb produced higher mortality. These effects could have affected different components of the vectorial capacity and similarly reduced malaria. PMID- 2098470 TI - Relative repellency of two formulations of N,N-diethyl-3-methylbenzamide (deet) and permethrin-treated clothing against Culex sitiens and Aedes vigilax in Thailand. AB - Field tests were conducted to compare the effectiveness of 2 repellent formulations of N,N-diethyl-3-methylbenzamide (deet) in combination with permethrin-impregnated military uniforms against Culex sitiens and Aedes vigilax in Thailand. Repellency was determined during a 2 h crepuscular period using volunteers who had been treated with repellents 6, 8, 10, and 12 h prior to the end of each test period. An extended-duration repellent formulation (EDRF) containing 35% deet repelled significantly more Ae. vigilax than 75% deet in ethanol. Although not statistically significant, the EDRF also resulted in fewer biting attempts by Cx. sitiens. Neither formulation provided complete protection against either species 4-12 h post-application, but both provided greater overall protection against Ae. vigilax. Volunteers who wore treated uniforms without repellents were attacked by significantly fewer mosquitoes than controls. PMID- 2098471 TI - Studies of the susceptibility of Anopheles albimanus and Anopheles vestitipennis from Dajabon, Dominican Republic, to insecticides. AB - Insecticide susceptibility of Anopheles albimanus and An. vestitipennis in Dajabon Province, Dominican Republic, was investigated. Only 74.3% of An. albimanus exposed to 4% DDT for 1 h died. The mortality in this species following exposure for 1 h to 0.25% permethrin was also 74.3%. However, this species was susceptible to malathion, fenitrothion and propoxur. The mortality obtained following exposure of An. vestitipennis to 4% DDT and 0.1% propoxur, both for 1 h, was 71% and 100%, respectively. However, the number of specimens exposed to propoxur was small. PMID- 2098472 TI - Bionomic studies of the Anopheles mosquitoes of Dajabon, Dominican Republic. AB - Field studies of Dajabon Province, Dominican Republic, revealed that Anopheles albimanus and An. vestitipennis were the most abundant anopheline species followed by An. crucians and An. grabhamii. Three of the species were collected as adults and larvae whereas An. grabhamii was found only in the adult stage. Perennial ponds and rice fields were the most important larval habitats. The anophelines were predominantly exophilic and exophagic; however, outdoor resting sites could not be identified. Large numbers of mosquitoes were collected from corrals at night and also by using an animal-baited net trap and UV light traps. Man-biting collections showed an early evening peak of biting activity by An. albimanus and An. vestitipennis. Only 23% and 13% of the bites by the 2 species, respectively, occurred indoors. PMID- 2098473 TI - Vertical transmission of St. Louis encephalitis virus to autogenously developed eggs of Aedes atropalpus mosquitoes. AB - Vertical transmission of St. Louis encephalitis virus was demonstrated by a strain of Aedes atropalpus mosquitoes from Garrett County, MD. Five-day-old parental females containing fully formed autogenous eggs were infected by intrathoracic inoculation. St. Louis encephalitis virus was detected in batches of fertilized eggs and fourth instar larvae. Estimated filial infection rates of approximately 1% were observed for both eggs and larvae. PMID- 2098474 TI - Daily survivorship of adult Aedes communis in a high mountain environment in California. AB - Using mark-release-recapture methods and linear regression analysis, daily survivorship for 3 groups of Aedes communis in a high mountain environment in the Sierra Nevada of California were estimated to be 0.90, 0.91 and 0.88, respectively. Multiple recaptures of marked females were made for up to 33 days after release. Precise estimates were not made of gonotrophic cycle lengths. However, parity data, based on dissections of samples of marked and unmarked females, suggest the length of gonotrophic cycles was between 1 and 2 weeks. PMID- 2098475 TI - Integrated use of planaria (Dugesia dorotocephala) and Bacillus thuringiensis var. israelensis against Aedes taeniorhynchus: a laboratory bioassay. AB - The effectiveness of integrating Bacillus thuringiensis var. israelensis (B.t.i.) and the predatory planaria, Dugesia dorotocephala against Aedes taeniorhynchus was determined under controlled laboratory conditions. There was no significant effect (P greater than 0.05) of B.t.i. on D. dorotocephala either by direct association or through ingestion of B.t.i. dosed larvae. Planaria, alone, and B.t.i. combined with planaria, both provided significant (P less than 0.05) reduction of Ae. taeniorhynchus populations through the 12-week evaluation. PMID- 2098476 TI - Genetics of golden-yellow larva in Anopheles stephensi. AB - Two larval body color mutants, golden-yellow larva (gy) and Black larva (Bl) were isolated from laboratory strains of Anopheles stephensi. The inheritance pattern revealed that golden-yellow larva was an autosomal recessive and Black larva an autosomal semi-dominant mutant. Both of these mutants were found to be linked with a map distance of 3.75 +/- 0.42 and have been placed in linkage group III. PMID- 2098478 TI - Evaluation of cyclopoid copepods for Aedes albopictus control in tires. AB - Six species of cyclopoid copepods in New Orleans were tested for biological control of Aedes albopictus larvae in discarded tires. Six to 8 weeks after introduction, Diacyclops navus, Acanthocyclops vernalis, Mesocyclops ruttneri and Mesocyclops edax reduced the number of Ae. albopictus larvae by 83, 90, 95 and 96%, respectively. Macrocyclops albidus and Mesocyclops longisetus were the most effective species. Six to 8 weeks after introduction, Macrocyclops albidus reduced Ae. albopictus larvae by 99%. Three months after introduction Macrocyclops albidus reduced Ae. albopictus larvae by 100%, and Mesocyclops longisetus reduced Ae. albopictus larvae by 99.8%. Macrocyclops albidus and Mesocyclops longisetus were equally effective at eliminating Ae. aegypti and Ae. triseriatus larvae. PMID- 2098477 TI - Tropical extension of temperature zone Culex pipiens throughout Egypt. AB - To explore the southern limit of the temperate zone form of the Culex pipiens complex of mosquitoes in North Africa, we compared the structure of the copulatory structures of such male mosquitoes sampled along the length of Egypt. Larval mosquitoes were collected in 11 sites distributed along the entire Egyptian span of the Nile Valley as well as in sites along the central Red Sea coast and in the western desert. Four of these sites were sampled repeatedly, at various times of the year. A DV/D ratio was calculated for each adult male mosquito. Although all DV/D values conformed to criteria normally attributed to the temperate zone form, even at the southernmost site (22 degrees N), values tended toward those of the tropical form in southern sites and during the summer months. We concluded that Cx. pipiens mosquitoes of the Middle East are predominantly Mediterranean in form due to an isolating effect of the Sahara Desert which separates these temperate zone insects from those of tropical Africa. PMID- 2098479 TI - Elimination of Aedes albopictus from tire piles by introducing Macrocyclops albidus (Copepoda, Cyclopidae). AB - The copepod Macrocyclops albidus is an unusually promising new form of biological control for mosquito larvae. When introduced to two isolated tire piles, M. albidus eliminated all Aedes albopictus larvae from both piles within 2 months. Adult Ae. albopictus around the tire piles disappeared within another month. Complete suppression of Ae. albopictus larvae was still in effect in all treated tires a year later. PMID- 2098480 TI - Efficacy of encapsulated Lagenidium giganteum (Oomycetes: Lagenidiales) against Culex quinquefasciatus and Aedes aegypti larvae in artificial containers. AB - Presporangial mycelia of Lagenidium giganteum cultured on sunflower seed extract were encapsulated in calcium alginate and added once (July 18) to outdoor (Raleigh, NC) caged tires, wood and concrete containers populated with first instars of Culex quinquefasciatus or Aedes aegypti. First instars were added twice weekly (for 10 wk) to simulate natural oviposition. The fungus persisted for 10 wk and recycled in the mosquito larvae of both species. The overall reductions of Cx. quinquefasciatus and Ae. aegypti immatures were higher in tires (55 and 45%, respectively) and wood (67 and 38%) than in concrete containers (17 and 14%). There were low correlations of the numbers of mosquito immatures with measurements of water quality (chemical oxygen demand, ammonia nitrogen and conductivity) in the containers. PMID- 2098481 TI - Seasonal distribution and biting patterns of Anopheles mosquitoes in Costa Marques, Rondonia, Brazil. AB - Thirteen species of anopheline mosquitoes were collected in all-night human-bait indoor and outdoor collections at 5 houses from July 1986 through December 1987 in and near the town of Costa Marques, Rondonia, Brazil. Anopheles darlingi and An. deaneorum accounted for more than 92 and 6%, respectively, of all anophelines collected from human-bait outside houses and 90 and 9%, respectively, inside houses in the town. The diversity of anophelines was greater in human-bait collections in rural areas. However, An. darlingi still accounted for more than 90% of all the anophelines collected from human-bait inside and outside rural houses. Data on nocturnal and seasonal biting rhythms for the more common anophelines are given. PMID- 2098482 TI - ULV droplet spectra: comparative analysis of six droplet collection methods. AB - Three distances (1.2, 3.0 and 7.6 m) and 4 methods (complete diagonal swing, impinger, top diagonal swing and vertical swing) were compared in analyzing the droplet spectra of electrically generated ULV aerosol clouds. There were no significant differences among the 4 methods and no interaction between method and distance. However, when compared over distance, the percent variability indicated the complete diagonal swing provided the most consistent results. Two additional methods (pendulum and settling chamber) were compared with the original 4 methods at 1.2 m only. At this distance, there was no significant difference among the 6 methods. PMID- 2098483 TI - A field evaluation of two suggested Aedes triseriatus oviposition attractants. AB - Two reported oviposition attractants for Aedes triseriatus, fish oil emulsion and water of high optical density, were evaluated in ovitraps in the field. Solutions of fish oil emulsion at 1% repelled ovipositing mosquitoes, whereas water containing vegetable dye increased oviposition up to 4-fold over control traps. Laboratory bioassays with fish oil emulsion at both 1 and 5% confirmed the field results. PMID- 2098484 TI - Evaluation of fenoxycarb against spring Aedes mosquitoes in Massachusetts. AB - The insect growth regulator, fenoxycarb, when applied at 0.06 kg AI/ha (0.05 lb AI/acre) as 1% sand granules was highly effective (97.5% corrected mortality) against Aedes communis, Ae. stimulans and Ae. canadensis in snowmelt pools in Massachusetts, and 100% effective against Ae. abserratus in an insectary study. No larval mortality owing to fenoxycarb treatment was observed, and most mortality occurred in the pupal stage as opposed to aborted adult emergence. PMID- 2098485 TI - Observations on installment egg hatching in the brown saltmarsh mosquito, Aedes cantator. AB - Field collected, first generation female Aedes cantator were shown to produce heterogeneous eggs that exhibit variable hatch in response to serial inundations and cold conditioning in the laboratory. Nearly 85% of the egg batches exhibited some hatch with the first flooding, representing 69.4% of the total overall hatch. However, 56% of the same egg batches displayed further hatch with subsequent floodings and 34% showed partial hatch before and after cold conditioning. The significance of these findings is discussed in relation to the biology of Ae. cantator. PMID- 2098486 TI - Pretreatment of floodwater Aedes habitats (dambos) in Kenya with a sustained release formulation of methoprene. AB - Effectiveness of sustained-release Altosid pellets (4% AI methoprene) against floodwater mosquitoes in dambos treated at 5, 3, and 1 wk before and 1 day after flooding was determined. Only 2% of Aedes pupae (primarily Aedes mcintoshi) survived to adults in an area treated 5 wk preflood, and no adult mosquitoes emerged from an area treated 1 day after flooding. In contrast, 12 and 16% of Aedes pupae successfully survived to the adult stage in areas pretreated 3 and 1 wk, respectively, preflood. The effectiveness of the Altosid declined against Culex spp. (primarily Cx. antennatus) collected from dambos 15-31 days after flooding. The potential for using preflood treatment with methoprene to control Aedes vectors of Rift Valley fever virus in endemic areas is discussed. PMID- 2098488 TI - Implant maintenance using a modified ultrasonic instrument. AB - With the increasing number of implants in place, oral hygiene and maintenance are imperative because implants are susceptible to plaque accumulation and calculus formation. This case study evaluated a modification of the common ultrasonic tip to remove calcified deposits on implant abutments and prostheses, and also evaluated ultrastructural changes on polished titanium. A modified "plastic" ultrasonic instrument was found to be clinically effective and efficient. This instrument, unlike a metal ultrasonic tip on an ultrastructural level, produced no irreversible changes on the evaluated commercially pure titanium test strip. The preliminary results of this modification of an ultrasonic instrument show promise for its use as an implant maintenance modality. PMID- 2098487 TI - Preceptorship: the impact on Georgia dental hygiene education. AB - The perceived imbalance between the supply of and demand for practicing dental hygienists has encouraged organized dentistry to pressure legislators for revisions in state practice acts. Georgia's recent experience with this type of legislation has required dental hygiene educators to develop, implement, and evaluate strategies that would increase the pool of available dental hygienists. The purpose of this paper is to present a review of strategies that were developed by Georgia dental hygiene educators to meet the recommendations spurred by proposed legislation in the General Assembly of Georgia. Dental hygiene program directors were charged by the chancellor of the University System of Georgia to improve student recruitment and retention, to explore the feasibility of new programs in areas of need, and to examine innovative ways to improve access to dental hygiene education. Dental hygiene faculties united with their professional association to activate alumni and registered hygienists, to improve public awareness by accentuating positive aspects of dental hygiene careers, and to organize a communication network whereby legislative information could be disseminated rapidly. Student recruitment was strengthened through individual and joint programs organized by dentists and dental hygienists. In response to these efforts, program enrollments were increased substantially, and a new program was established in an area of need. Nationally, dental hygienists are facing many challenges and problems that threaten to weaken or eliminate their status as educated and competent health professionals. Recently, dental and dental hygiene educators' attention was drawn to legislative activity in Georgia. PMID- 2098489 TI - Admissions criteria predictors of dental hygiene graduates' job satisfaction. AB - The relationship of a dental hygiene program's admissions criteria to its graduates' subsequent job satisfaction was examined. One hundred thirteen subjects who had graduated from an associate degree-granting dental hygiene program between the years 1977 and 1986 responded to a mailed questionnaire that obtained demographic information and job satisfaction measures. The admissions criteria were collected from records on file at the dental hygiene program. Responses to the Minnesota Job Satisfaction Questionnaire (MSQ) were tabulated to obtain a general job satisfaction score and to obtain selected job satisfaction subscale scores on variety, compensation, advancement, and achievement. It was hypothesized that there would be no relationship between the admissions criteria and the selected job satisfaction scale scores. A total of five stepwise multiple regression analyses was performed, with each of the five satisfaction scale scores as the dependent variable and the admissions criteria entered as independent variables. No variables were entered into a regression equation, as no correlations were significant at p less than .05. A one-way analysis of variance (ANOVA) with the general job satisfaction percentile score as the dependent variable and year of graduation as the independent variable was conducted. When combined as groups, those who graduated in the first five years (1977-81) expressed statistically significant lower general job satisfaction (p = .0072) than the graduates from 1982-1986. The analysis of the admissions criteria and job satisfaction scores must be looked at cautiously, as the sample was limited to graduates from a particular dental hygiene program. PMID- 2098490 TI - Predictors of position of intellectual development in dental hygiene students and practitioners. AB - The purpose of this study was to investigate the relationship between verbal ability, age, extent of education and professional experience (separately and in combination), and level of cognitive development of dental hygiene students and practitioners. Forty-five dental hygiene students and graduates (15 associate degree subjects without professional experience; 15 associate degree subjects with professional experience; and 15 baccalaureate degree subjects with professional experience) participated in this cross-sectional study. The Measure of Intellectual Development (MID), a semi-structured, generation cognitive task, was used to assess cognitive development (position/stage of intellectual development). MID protocols were scored separately and blindly by two raters resulting in high interrater reliability and agreement estimates. In general, subjects were functioning at a relatively low level (position 3 multiplicity) of cognitive development. Baccalaureate degree subjects tended to function at a higher position than subjects in the other two groups. There was a significant, positive correlation between extent of education and level of cognitive development. PMID- 2098491 TI - Consumers' awareness of barrier protection in dentistry. AB - Because of the scarcity of printed educational material available to the oral healthcare consumer regarding barrier protection in the dental office, four students at the Fones School of Dental Hygiene conducted a senior project that hypothesized that dental health consumers are poorly informed about barrier protection. Data received from a questionnaire were analyzed to determine the participants' awareness of barrier protection in the dental care setting; specifically, the use of masks, gloves, and protective eyewear. Of the 400 participants, 72% reported that their dentist wore gloves. Of the 321 participants who indicated that their dentist employs a dental hygienist, 76% reported that the dental hygienist wears gloves. And of the 334 participants who indicated that their dentist employs a dental assistant, 65% reported that their dental assistant wears gloves. The percentage of participants who reported the use of protective eyewear and masks is lower. Survey participants who visited offices where dental hygienists and dental assistants are employed were more likely to notice the dentist wearing a mask, gloves, and protective eyewear. Eighty-nine percent of the participants replied that they knew why masks, gloves, and protective eyewear should be worn in the dental setting; 40% replied that they would like more information. PMID- 2098492 TI - Advances in biology and treatment of malignant brain tumors. Proceedings of the Second Meeting of Neuro-Oncology. Rome, November 16-18, 1989. PMID- 2098493 TI - Neurocytogenesis and tumor development in the rat. AB - The occurrence of vimentin-positive and GFAP-negative cells in gliomas induced by transplacental ENU in the rat is not yet clarified. Because of the temporal overlapping between neural cytogenesis and tumoral transformation in this experimental model, the expression of vimentin and GFAP in the developing rat brain can give some information. Vimentin is constantly present in the processes of radial glia; the earliest GFAP-positive cells are mature astrocytes appearing when vimentin-positive radial glia is still abundantly present. Transitional immunoreactivity from radial glia to stellate astrocytes, also with double staining in immune electronmicroscopy, is not demonstrable; the role of radial glia as a precursor cell to mature astrocytes is not confirmed. It can be hypothesized that radial glia is a target of ENU, and that its pattern of intermediate filaments is maintained in the tumor phenotype. PMID- 2098494 TI - Oncogenes and growth factors in gliomas. AB - The activation of cellular proto-oncogenes is related to the genesis and progression of neoplasias. Protein growth factors and their cellular receptors have been identified as products of some proto-oncogenes. The role of epidermal growth factor receptor (EGFr) in gliomas is presented. The expression of mRNA for platelet-derived growth factor (PDGF) and PDGF B-type receptor (PDGF-rec-B) in gliomas is analyzed. Gliomas express "in vivo" PDGF.B and PDGF-rec-B mRNAs. PDGF.B mRNA levels correlate with GFAP mRNA and does not correlate with the degree of malignancy. This is in agreement with the hypothesis of an autocrine growth stimulation in gliomas. However some findings seem to indicate that in these tumors the PDGF-rec-B is preferentially expressed by vascular elements. Thus, also a paracrine loop for endothelial cell growth stimulation may be suggested in malignant gliomas. PMID- 2098495 TI - Preferential expression of the dbl proto-oncogene in some neuroectodermal tumors. AB - The dbl oncogene belongs to a unique class of human transforming genes. The dbl proto-oncogene is activated by substitution of the 5' portion of the gene with an unrelated human sequence. The proto-oncogene product is distributed between the soluble and membrane fractions of the cytoplasm and its function remains still unknown. In order to understand the biological role of dbl in human malignancies or during cell differentiation we have investigated the expression of the dbl oncogene in a wide number of human tumors of different embryological derivation. We found that dbl is preferentially expressed in a few neoplastic histiotypes of neuroectodermal origin. The transcript size of 5.3 Kb strongly suggests that the gene is not truncated in these tumors. These data, together with the information that the proto-oncogene has been found expressed in normal brain and adrenal medulla, indicate that dbl expression may be involved in cell differentiation of some tissues of neuroectodermic origin. PMID- 2098496 TI - Role of autocrine stimulation in a glioma cell line. AB - It has recently been shown that autocrine stimulation can play a pivotal role in the development and progression of a variety of neoplasms, including malignant gliomas. In this paper is reported how a glioma cell is able to be stimulated by basic fibroblast growth factor (bFGF) and, at the same time, to produce a growth factor which shares with bFGF many biological and biochemical properties. PMID- 2098497 TI - The progression in astrocytic tumors. AB - Progression represents the qualitative tumor evolution during the time. Recently it received great consideration, mainly since the introduction of the neuroradiological imaging (CT and MRI). A series of 224 supratentorial astrocytic tumors of the juvenile and adult age have been analyzed: we found the morphological features of progression in 26% of them. These data introduce, perhaps, the most important information about progression: the "crisis" of the concept that low-grade tumors are stable lesions during the time. PMID- 2098498 TI - The membrane-bound hexokinase as a potential marker for malignancy in human gliomas. AB - Hexokinase is a key enzyme in carbohydrate metabolism. Its activity has been shown elevated in cells with high mitotic index. In particular, experimental cancer cells, due to their peculiar energy metabolism, display a hexokinase activity proportional to the degree of malignancy. This is the case also for human gliomas in which glucose metabolism, evaluated via positron emission tomography, has been shown to be predictive for patient prognosis. In order to better correlate these findings, specific reagents for tumor hexokinase (a polyclonal antibody and a full-length cDNA probe both specific for murine tumor hexokinase) have been successfully employed to quantitate the protein and its messenger in cultured cell lines; the antibody was also tested in four specimens obtained from human astrocytomas. PMID- 2098499 TI - Effect of x-radiation to brain on cerebral glucose utilization in the rat. AB - We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- cGy/day given 5 days a week) to a total dose of 4000 cGy. Metabolic experiments were made 2 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, brain areas with the highest basal metabolic rates showed the greatest percentage drop of glucose utilization. Post-irradiation metabolic alterations possibly provide an explanation for the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy. PMID- 2098500 TI - The role of immunocytochemical assays in the diagnosis of stereotactic biopsies from intracranial tumors. AB - A selected panel of monoclonal antibodies (MoAbs) directed to distinct tumor associated antigens (TAA) has been tested to define the capability of these reagents to differentiate among metastatic carcinoma, lymphoma and primary brain tumor on cytologic specimens obtained with stereotactic techniques. Results obtained on 50 patients bearing either single or multiple brain lesions demonstrated that immunocytochemical (ICC) methods can distinguish between primary brain tumor and brain metastasis suggesting, in 90% of patients with cryptic primary neoplasia, the site of origin of the tumor. PMID- 2098501 TI - Prognostic relevance of hormonal and kinetic parameters in CNS neoplasms. AB - With the present study we investigated both the presence of cytoplasmic estrogen (E-Rc) and progesterone (P-Rc) receptor, nuclear E-R (E-Rn) and the percentage of cycling tumor cells with Ki-67 MAB in 32 CNS tumor specimens. The main purpose of our study was to evaluate a possible correlation between the hormonal and kinetic parameters and the clinical and neuroradiological follow-up. PMID- 2098502 TI - Histologic and clinical factors of prognostic significance in astrocytic gliomas. AB - The three-tiered system of classification of astrocytic gliomas that distinguishes the well differentiated astrocytoma, the anaplastic astrocytoma and the glioblastoma seems to better correlate with outcome. The knowledge of factors (histologic, clinical, radiologic and therapeutic) affecting survival in both well differentiated and anaplastic astrocytomas is limited. In both types young age and high performance status are associated with a better prognosis. The prognostic value of many factors in well differentiated tumors is still debated: this is the case for the number of mitoses, the enhancement on CT, the extent of surgery and the usefulness of postoperative radiotherapy. In anaplastic astrocytomas there is agreement about the prognostic value of endothelial proliferations: their presence is correlated with a poor prognosis. Post operative radiotherapy (5.500-6.000 cGy) significantly improves the survival time, whereas is still not known the true value of the extent of resection. PMID- 2098503 TI - Utility and limits of an imaging follow-up in evaluation of response and evolution of cerebral tumors after radiotherapy. AB - CT scans of 110 patients with malignant gliomas treated with radiotherapy, postoperative or alone, were reviewed. Our aim was to assess the utility and limits of an imaging follow-up in evaluating tumor response to treatment and evolution. We have tried to define the densitometric parameters of tumors in various evolutive phases, with special emphasis on variations of contrast enhancement during time. CT scan findings were compared with clinical and therapeutic data. PMID- 2098505 TI - Immunotherapy of brain tumors. AB - In the process of malignant transformation, astrocytoma cells display a number of surface antigens not expressed by their normal adult counterparts and which have been identified by monoclonal antibodies and characterized biochemically. These include tumor associated antigens (TAA) such as oncofetal antigens of neuroectodermal origin or oncogene products such as epitopes in the extracellular domain of the epidermal growth factor receptor, as well as major histocompatibility antigens (MHC) of class I and class II. Glioma cells also secrete lymphokines like IL-1 and IL-6. The concomitant expression of TAA and MHC together with the disruption of the blood brain barrier may elicit a humoral or cell mediated immune response from the tumor bearing host as demonstrated by the functional analysis of tumor infiltrating lymphocytes. However this response is extremely weak and obviously inefficient because the tumor cells secrete factors which can inhibit or completely abrogate the immune attack by cytotoxic T cells. Among these factors, TGF-beta 2 and PGE2 are of particular interest since they may explain the generally depressed cellular immune response observed in patients with malignant gliomas. To be efficient any form of immunotherapy will require abatement of these suppressive activities in addition to stimulation of the effector functions. PMID- 2098506 TI - Surgical therapy of malignant gliomas. AB - The authors have presented the current state of surgical therapy of malignant gliomas underlining the advantages and disadvantages of traditional and stereotactic surgery, preparation for surgery, mortality, morbidity, prognostic factors, and complications. Particular attention was placed on cell kinetic studies. Of the methods used in this study we would like to recall those of flow cytometry associated with administration of BUdR and utilization of the monoclonal antibody Ki-67 associated with immunohistochemical techniques. PMID- 2098504 TI - Lonidamine in the combined treatment of malignant gliomas. A randomized study. AB - Lonidamine (LND) is a drug that interferes with energy metabolism of cancer cells, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK). In such way LND could impair energy requiring processes, as recovery from potentially lethal damage, induced by radiation treatment and by some cytotoxic drugs. A randomized study started in November 1983, to evaluate the efficacy of LND in association with radiotherapy as first line treatment in malignant gliomas, after surgical procedure. LND was also used in association with Lomustine (CCNU) at the moment of documented clinical and neuroradiological recurrence. At the present time 60 patients entered the study, and 47 are evaluable. Present preliminary results are not statistically significant, however indicate that LND tends to prolong the median survival time and the rate of one year survivors. PMID- 2098507 TI - Experience in "radical" surgery of supratentorial gliomas in adults. AB - This study reports the preliminary results obtained in a series of 107 patients with histologically proven malignant gliomas (86 glioblastomas and 21 anaplastic astrocytomas) operated upon between 1986 and 1989, with an aggressive attitude aimed to achieve extensive and possible "radical" excision of the tumor. Gross total removal was achieved in 62% of cases, while in the remaining the postoperative contrast enhanced CT scan showed more than 10-15% of residual tumor mass. There was no operative and postoperative mortality. The one-year survival rate was 60% in patients with total removal and 24% in those with partial resection. Furthermore the Karnofsky rating at discharge was improved in the former group while was unchanged in the latter. Although preliminary, these data seem to confirm the primary positive role of radical surgery in the combined management of malignant gliomas. PMID- 2098508 TI - Intracranial tumors of the first year of life. AB - The introduction of new diagnostic tools for neuroimaging has resulted in the early recognition of congenital brain tumors. In the present report we describe a personal series of 39 children and an International Multicenter Series of 876 children with brain tumors, in whom the diagnosis was obtained during the first 12 months of life. Most of the tumors were located within the supratentorial compartment. In spite of a relatively high operative mortality, surgery still appears to be the more effective therapy. Radiotherapy in this age group is of a scarce value, due to the vulnerability of the infantile brain. At the present time, chemotherapy still plays a controversial role. PMID- 2098509 TI - Surgical treatment of paediatric malignant neuroepithelial brain tumors. AB - The role of the neurosurgeon in dealing with malignant neuroepithelial brain tumors, both supra- and infratentorial, in paediatric age, is stressed; this because surgery is the main therapy, and also it is mandatory, in order to achieve the pathological diagnosis, essential for planning any kind of complementary treatment. Open surgery versus stereotactic biopsy is considered, with emphasis on brain stem tumors. The treatment of malignant tumor recurrencies is also discussed, and the indications of a second surgical look in patients harboring recurrent medulloblastoma is proposed for discussion, when long disease free time occur and combined modality treatments are performed. PMID- 2098510 TI - Surgical treatment of 100 single brain metastases. Analysis of the results. AB - The authors report their personal series of 100 consecutive surgically treated single brain metastases between 1981 and 1988. Patients selection was decided with respect to general and neurological conditions and to primary cancer development. Resection was mostly radical, postoperative mortality rate was 6% and neurological improvement was obtained in 73% of cases. Mean follow-up was 15 months (min. 12, max. 60). The overall median survival time was 13 months. The survival rate was studied with respect to age, lesion site, preoperative syndrome, primary cancer, cause of death and radiotherapy. On the base of their experience the Authors would stress that a better patients selection can further reduce the mortality rate. PMID- 2098512 TI - Stereotactic support in the excision of brain tumors. Technical note. AB - The surgical resection of deep-seated brain tumors may be facilitated by CT guided stereotactic methods. The Authors present a procedure of preoperative localisation and delimitation of the border of a neoplastic mass facing important functional areas. Ideally tumor excision should not be extended beyond that boundary which for this reason is targeted and is stereotactically labeled using non diffusible dyes. PMID- 2098511 TI - Brain metastases: surgical versus conservative treatment. AB - A comparative study on surgical versus conservative brain metastases treatment has been carried out. Patients have been divided in seven groups by means of treatment modalities. Follow-up, has been carried out taking into consideration mean survival time and quality life in particular, evaluated by means of Order's classes. Anaesthesiological management problems were discussed also. From data analysis, it follows that untreated patients, (group 1) had a lower mean survival time than that of the other patients. Thirty days after first evaluation, 85% of these patients had a very poor quality life. Patients who underwent surgery associated to radio and chemotherapy (group 2) have had better recovery of functional autonomy and longest mean survival time. Among these, thirty days after treatment only 3% had a very poor quality life, while 67% had the better quality life. Patients who underwent others treatment modalities had intermediate results. PMID- 2098513 TI - A case of optic nerve oligodendroglioma associated with an orbital non-Hodgkin's lymphoma in adult. Case report. AB - The Authors report a case of optic nerve oligodendroglioma associated with an orbital non-Hodgkin's lymphoma. Its peculiar clinical aspects and neuroradiological appearance are discussed. PMID- 2098514 TI - A case of multifocal cerebellar medulloblastoma in an adult patient. PMID- 2098516 TI - Biochemical and molecular aspects of aromatase. PMID- 2098515 TI - The effect of brain radiotherapy on the P3 component of ERP's. AB - Nine patients with lung cancer without brain metastasis were studied pre and post brain prophylactic radiotherapy (30 Gy) to verify the effect of radiation on the cognitive processes. The P3 component of event-related potentials was used in this study. The latencies pre and post-radiation were compared and a significant delay (p less than 0.01) was detected in patients after treatment. These results suggest that brain radiotherapy may produce a cognitive impairment, as reported by many Authors. PMID- 2098517 TI - 7-substituted steroidal aromatase inhibitors: structure-activity relationships and molecular modeling. AB - Androstenedione analogs containing 7 alpha-substituents have proven to be potent inhibitors of aromatase both in vitro and in vivo. Several of these agents have exhibited higher affinity for the enzyme complex than the substrate does. In order to examine further the interaction(s) of 7-substituted steroids with aromatase, biochemical and molecular modeling studies were performed on 7 substituted 4,6-androstadiene-3,17-diones. 7-Benzyl- and 7-phenethyl-4,6 androstadiene-3,17-diones effectively inhibited microsomal aromatase, with apparent Kis ranging from 61 to 174 nM. On the other hand, 7-phenyl-4,6 androstadiene-3,17-dione exhibited poor activity, with an apparent Ki of 1.42 microM. Energy minimization calculations and molecular modeling indicated that the 7-substituent is perpendicular to the steroid nucleus in the 7-phenyl analog and can only adopt a pseudo beta position. The 7-benzyl- and 7-phenethyl- groups of 4,6-androstadiene-3,17-diones orient themselves in the minimized structure in a way that the phenyl rings can protrude into the 7 alpha pocket. These orientations are similar to those observed in minimized structures for potent 7 alpha-substituted androstenediones. PMID- 2098518 TI - Synthesis and biochemical evaluation of the novel steroid androsta-4,6,8(9) triene-3,17-dione. AB - According to a proposed aromatisation mechanism by which estrogens are biosynthesized from androgens, the novel steroid androsta-4,6,8(9)-triene-3,17 dione (FCE 24918) should behave as a suicide substrate for aromatase. The synthesis of this triene steroid has been accomplished starting from androsta-4,7 diene-3,17-dione (4) by the acid-catalysed cleavage of the corresponding 7,8 alpha-epoxide, 5, and it was obtained together with androsta-4,6,8(14)-triene 3,17-dione (FCE 24917) as a side product. The time-dependent inactivation of placental aromatase by the two isomers was studied comparatively and showed that the 4,6,8(9)-triene moiety acts as a latent alkylating group. PMID- 2098519 TI - Synthesis of 2,2-dimethyl-4-hydroxy-4-androstene-3,17-dione as an inhibitor of aromatase. AB - 2,2-Dimethyl-4-hydroxy-4-androstene-3,17-dione (4) has been synthesized and has been shown to be a powerful competitive inhibitor of aromatase (Ki = 11.4 nM). However, compound 4 does not cause time-dependent loss of enzyme activity, in contrast to the unmethylated parent compound, 4-OHA. PMID- 2098520 TI - Enzyme inactivation by potential metabolites of an aromatase-activated inhibitor (MDL 18,962). AB - MDL 18,962, 19-acetylenic androstenedione, is an enzyme-activated inhibitor of estrogen biosynthesis which is in Phase I clinical evaluations as a potential therapeutic agent for estrogen-dependent cancers. 19-Acetylenic analogs corresponding to the major metabolites of androstenedione were synthesized as potential metabolites of MDL 18,962. These compounds were 19-acetylenic testosterone, the product of 17 beta-hydroxy steroid oxidoreductase, 6 beta hydroxy- and 6-oxo-19-acetylenic androstenedione, products of P450 steroid 6 beta hydroxylase and alcohol dehydrogenase, respectively. All of these analogs showed time-dependent inactivation of human placental aromatase activity. The time dependent Ki and t1/2 at infinite inhibitor concentration (tau 50) were 4.3 nM, 12.0 min for MDL 18,962; 28 nM, 7.8 min for 17-hydroxy analog; 13 nM, 37 min for 6 beta-hydroxy analog; and 167 nM, 6.1 min for the 6-oxo analog. The 19 acetylenic testosterone, a confirmed metabolite from primate studies, was 25% as efficient as MDL 18,962 for aromatase inactivation, while 6 beta-hydroxy- and 6 oxo analogs were 11% and 5%, respectively as efficient as their parent compound. These data indicate that first-pass metabolism of MDL 18,962 does not cause an obligatory loss of time-dependent inhibition of human aromatase activity. PMID- 2098521 TI - The effects of in vivo administration of 10-propargylestr-4-ene-3,17-dione on rat ovarian aromatase and estrogen levels. AB - We have previously demonstrated that 10-propargylestr-4-ene-3,17-dione (PED) functioned as an irreversible inhibitor of rat ovarian aromatase in vitro. These studies were undertaken to examine the in vivo effects of PED on rat ovarian aromatase activity and estrogen production. In the current experiments, a single injection of PED (0.5 or 2.5 mg/kg) was found to maximally inhibit aromatase at 3 h regardless of dose. Significant inhibition of enzyme activity by PED was observed beyond 18 h, although some recovery was noted at the lower dose (0.5 mg/kg). Concomitantly, ovarian estrogen levels were also maximally reduced at 3 h, however ovarian estrogen levels returned toward control values prior to the recovery in enzyme activity. Even though significant inhibition of enzyme activity was observed at 12 h following a single injection of PED, the effect of double injections of the inhibitor at 12 h intervals was surprisingly not cumulative. Similarly, continued multiple injections of PED revealed significant inhibition of enzyme activity and estrogen production several hours after the injection, but variations in effectiveness were observed by 12 h which changed in accordance with a circannual cycle in aromatase. Apparently other factors are involved with maintaining aromatase levels and compensating for reduced enzyme activity. These mechanisms are evidenced by a continuation of the rat reproductive cycle with prolonged PED administration and a reduced influence of PED in regard to enzyme inhibition at certain times of the year. Despite these variations in the duration of action of PED, no comparable changes were observed in effectiveness as an anti-tumor agent. These results suggest that complex mechanisms exist which regulate the activity of aromatase in order to maintain estrogen production. Further research using compounds such as PED may assist in elucidating the factors that modulate ovarian estrogen production. PMID- 2098522 TI - Endocrine and antitumoral effects of R76713 in rats. AB - Some effects of daily oral administration of a new non-steroidal aromatase inhibitor on the pituitary-gonadal and adrenal functions were investigated in female rats. At doses of 1 mg/kg twice daily or higher, R 76713 lowered plasma estradiol levels to the range measured after ovariectomy Plasma progesterone levels and uterine weights decreased whilst LH levels increased but to a lesser extent than after ovariectomy. The other hormonal data show that long-term administration of R 76 713 does not modify the gluco- and mineralocorticoid hormone levels even at the highest dose studied (20 mg/kg, 4 h after treatment). Furthermore, both ovariectomy and R 76 713 treatment (1 and 5 mg/kg twice a day) induced almost complete regression of 9,12-dimethyl-1,2-benzanthracene-induced mammary carcinoma in rats. The appearance of new tumors during the treatment period was completely inhibited by R 76 713 whilst multiplicity of the remaining tumors was dramatically reduced. PMID- 2098523 TI - Inhibition of aromatase in vitro and in vivo by aromatase inhibitors. PMID- 2098525 TI - Aromatase inhibitors: introduction and perspective. PMID- 2098524 TI - Aromatase inhibitors in cigarette smoke, tobacco leaves and other plants. AB - A chance observation that cigarette smoke interferes with the aromatase assay led us to investigate tobacco leaf and smoke extracts for the presence of aromatase inhibitors. The highest inhibitory activity was found in the basic fraction of cigarette smoke. Further purification of this fraction led to the identification of N-n-octanoylnornicotine. Synthesis and testing of a series of acylated nornicotines and anabasines for their ability to inhibit aromatase showed an interesting correlation of activity with the length of the acyl carbon chain, with maximum activity at C-11. The acylated derivatives showed activity which was significantly greater than that of nicotine and anabasine. In vivo studies in rats indicated that administration of this inhibitor delayed the onset of NMU induced breast carcinoma and altered the estrus cycle. These in vivo studies suggest that tobacco alkaloid derivatives exert their effects by suppression of the aromatase enzyme system. Toxicity studies indicated relatively low toxicity with LD50 for N-n-octanoylnornicotine = 367 mg/kg body weight. When extracts from thirty five varieties of vegetables, plant leaves, and fruits were analyzed, seventeen showed quantitatively significant aromatase inhibition which was comparable to that of green tobacco leaf, suggesting that naturally occurring substances may affect endocrine function through aromatase inhibition. PMID- 2098526 TI - Clinical use of aromatase inhibitors: current data and future perspectives. PMID- 2098527 TI - Another five years of dental litigation: 1985-1989. PMID- 2098528 TI - Ethics and health care in capitalism. AB - Rising health-care costs can cause problems in a capitalistic society because they can result in the diversion of funds from new product development. Presently, $500 billion is spent on healthcare, and there are signs that certain treatments are being reduced because of expense. This overall cost reduction will probably impact dentistry most because dentistry is viewed as more discretionary than medical healthcare. Rewarding for systematic prevention in the office is the most ethical solution if treatment funds are reduced. PMID- 2098529 TI - Federal Trade Commission antitrust enforcement in the dental profession. PMID- 2098530 TI - Guide to the law for practitioners of dentistry and medicine. I: The system of law. Chapter 3: How the courts function. PMID- 2098532 TI - Modern day alchemy: Changing silver to plastic. PMID- 2098531 TI - Comprehensive care clinics: an alternative approach in clinical dental education. PMID- 2098533 TI - Drug prescription liability. PMID- 2098534 TI - Who can testify? PMID- 2098535 TI - Suspension of license upheld. PMID- 2098537 TI - Covering doctors: who is liable? PMID- 2098536 TI - California clarifies doctrine of informed refusal. PMID- 2098538 TI - Taking it all off. PMID- 2098539 TI - Insurance fraud. PMID- 2098540 TI - Major medical covers dental treatment in TMJ cases. PMID- 2098541 TI - Lost records. PMID- 2098542 TI - New York requires continuing education in recognizing and reporting child abuse. PMID- 2098543 TI - Florida requires continuing education in AIDS. PMID- 2098544 TI - Dose-dependent shift in acyl glucuronidation and glucosidation of pranoprofen, a 2-arylpropionic acid derivative, in mice in vivo. AB - Following the oral administration of [14C]pranoprofen to mice, 70-80% of radioactivity was excreted in the urine, and 15-25% in the feces within 3 d at 5, 25, 50, 100 and 200 mg/kg. This showed that no significant change in urinary and fecal excretion was observed among these doses. The radioactivity levels in the blood also increased in proportion to the doses, indicating that no repression of the absorption of pranoprofen was found even at increased doses. The major metabolites in mouse urine were acyl glucuronide and the glucoside of pranoprofen. At low doses acyl glucoside was predominantly excreted in urine, whereas acyl glucoside decreased relative to acyl glucuronide at increased doses. Although 43.2% of the acyl glucoside was recovered in the 24 h urine samples after the intravenous administration of acyl glucuronide, no acyl glucuronide was found in the urine after the intravenous administration of acyl glucoside. These results demonstrated the interesting observation that pranoprofen had a preference for glucosidation rather than glucuronidation in mice at low doses in spite of having a higher capacity of glucuronidation. PMID- 2098545 TI - Acyl glucuronidation and glucosidation of pranoprofen, a 2-arylpropionic acid derivative, in mouse liver and kidney homogenates. AB - The formation of acyl glucuronide and glucoside of 2-(5H-[1]benzopyrano[2,3 b]pyridin-7-yl)propionic acid (pranoprofen), an anti-inflammatory drug, was studied in homogenates and microsomes of mouse tissues by using S(+)-, R(-)- and RS(+/-)-pranoprofen. Acyl glucuronidation occurred mainly in the liver, whereas acyl glucosidation was predominant in the kidney. Furthermore, both conjugations occurred by enzymatic transfer of glucuronic acid of uridine diphosphate glucuronic acid (UDPGA) and glucose of uridine diphosphate glucose (UDPG) to pranoprofen, respectively. No conjugation reactions were observed in the lung, plasma or gut. The amount of conjugates in the liver and kidney increased by the prolongation of the incubation times and reached the maximum at 15-30 min for glucuronidation and 45 min for glucosidation. After that, both conjugates decreased with the lapse of time. Both acyl conjugates were the least stable in the liver, then in the kidney and the most stable in the plasma. In the liver, acyl glucoside was converted to acyl glucuronide and pranoprofen in the presence of UDPGA, but only a small amount of acyl glucuronide was changed to acyl glucoside in the kidney in spite of the presence of UDPG. In the kidney, acyl glucoside decreased relative to acyl glucuronide at increasing doses for both S(+)- and R(-)-pranoprofen, but the concentration of acyl glucoside was much higher for S(+)-pranoprofen than R(-)-enantiomer 1 h after the oral administration of S(+)- and R(-)-pranoprofen. No acyl glucoside was detected in the liver and plasma. Although only a small difference in acyl glucuronidation in the liver was observed between S(+)- and R(-)-enantiomers, acyl glucosidation in the kidney occurred more predominantly for S(+)-pranoprofen than for the R(-) enantiomer. PMID- 2098546 TI - Stereoselective acyl glucuronidation and glucosidation of pranoprofen, a 2 arylpropionic acid derivative, in mice in vivo. AB - Following the oral administration of RS(+/-)-pranoprofen to mice at a dose of 25 mg/kg, 10.7% of the acyl glucuronide and 46.4% of the acyl glucoside of pranoprofen were excreted in the urine within 24 h. The recovery of acyl glucoside in the urine decreased relative to that of acyl glucuronide at increasing doses (100, 200 mg/kg). Following the oral administration of S(+) pranoprofen to mice at a dose of 25 mg/kg, 5.0% of the acyl glucuronide and 56.5% of the acyl glucoside were excreted in the urine within 24 h, while 10.8% of the acyl glucuronide and 13.9% of the acyl glucoside were excreted after the oral administration of R(-)-pranoprofen, respectively. The absolute configuration of the aglycone of acyl glucuronide was almost R(-)-enantiomer (92.5-96.1%) in the 0 24 h urine, whereas that of acyl glucoside contained 15.3-24.7% of S(+) enantiomer after the oral administration of R(-)-pranoprofen. On the other hand, only the S(+)-isomer was found as the aglycone of both acyl glucuronide and glucoside after the oral administration of S(+)-pranoprofen. The present results showed that stereoselective conjugation was observed in glucosidation in mice. Nevertheless, a dose-dependent shift in glucuronidation and glucosidation was found for both the administrations of S(+)- and R(-)-enantiomers as well as RS(+/ )-pranoprofen. Also a chiral inversion of R(-)-enantiomer to S(+)-antipode may occur slightly but significantly in mice. PMID- 2098547 TI - Species differences in absorption, metabolism and excretion of pranoprofen, a 2 arylpropionic acid derivative, in experimental animals. AB - Absorption, metabolism and excretion of 2-(5H-[1]benzopyrano-[2,3-b]pyridin-7 yl)propionic acid (pranoprofen), an anti-inflammatory drug, were investigated in mice, rats, guinea pigs and rabbits using 14C-labeled compound ( [14C]pranoprofen) at a dose of 5 mg/kg. After the oral administration of [14C]pranoprofen the radioactivity was rapidly and almost completely absorbed from the digestive organs of the animals tested. The radioactivity in the blood reached the maximum at 30--60 min after the oral administration of [14C]pranoprofen in all species tested, and the biological half-lives of the radioactivity were 4.1 h in rats, 2.6 h in guinea pigs, 1.3 h in mice and 0.9 h in rabbits, respectively. When [14C]pranoprofen was orally administered, urinary and fecal excretions of the radioactivity within 3 d were 81.1% and 18.7% of the dose in mice, 51.5% and 39.4% in rats, 81.8% and 9.0% in guinea pigs, and 93.2% and 3.6% in rabbits, respectively. A major metabolite of pranoprofen was its acyl glucuronide in rats, guinea pigs and rabbits. However, it was shown that acyl glucosidation is also a predominant metabolic pathway of pranoprofen in mice. PMID- 2098548 TI - Improvement by adjuvants on the rectal bioavailability of non-absorbable drugs following administration of suppository. AB - The influence of suppository bases and adjuvants on the release rate of drugs and the absorption of non-absorbable drugs such as sulfanilic acid (SA) and sulfaguanidine (SG), was investigated following the rectal administration of suppositories. The suppository bases used were lipophilic bases such as Witepsol W 35, H 15, S 55, E 75 and hydrophilic base such as macrogol. SA was rapidly released from macrogol, W 35, H 15 and S 55, except E 75. On the other hand, SG was rapidly released from macrogol, whereas the release of SG from lipophilic bases was slow. Rectal absorption of SA and SG following administration of each drug alone in suppository form was slight. On the addition of diclofenac sodium (DF) as absorption promoter the blood levels of SA and SG released from all suppositories increased by about two to four fold compared with those suppositories containing only SA or SG, respectively. However, the absorption of SG still did not attain sufficient levels by the administration of DF only. The rectal absorption of SG was markedly increased by the release rate of the drug from the suppository. These results indicate that after administration of these suppositories the bioavailability of non-absorbable drugs was sufficiently improved by enhancing both the release rate from the suppositories and the rectal membrane permeability. PMID- 2098549 TI - Production of angiotensin-converting enzyme inhibitors from baker's yeast glyceraldehyde-3-phosphate dehydrogenase. AB - Angiotensin-converting enzyme (ACE) inhibitors were excised from the molecule of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) preparation of baker's yeast by heating at 120 degrees C in 1 M AcOH-20 mM HCl. Three inhibitors were then purified by gel-permeation and reverse-phase chromatographies. One of the yeast ACE inhibitors, YG-3, was GAPDH peptide 79-89 (Pro-Ala-Asn-Leu-Pro-Trp-Gly-Ser Ser-Asn-Val, IC50:18 microM), and contained the sequence homologous to vertebrate ACE inhibitors (GAPDH peptides 79-86 or 81-88). Other inhibitors, YG-1 (Gly-His Lys-Ile-Ala-Thr-Phe-Gln-Glu-Arg, IC50: 0.4 microM) and YG-2 (Gly-Lys-Lys-Ile-Ala Thr-Tyr-Gln-Glu-Arg, IC50: 2 microM), corresponded to amino acid residues 68-77 in two different forms of yeast GAPDH, respectively. Their sequences were quite different from those of the venom peptide family. YG-1 was the most potent ACE inhibitor among yeast and vertebrate GAPDH peptides excised by acid-limited proteolysis. Thus, yeast GAPDH seems to be an excellent source of naturally occurring ACE inhibitors. PMID- 2098550 TI - Effects of cholinergic drugs and cerebral metabolic activators on memory impairment in old rats. AB - Age-related changes in the acquisition and retention of memory based on the step through active avoidance response were studied in rats and the effects of cholinergic drugs and cerebral metabolic activators on memory impairment in old rats were also tested. Six- and 12-month-old rats showed lower rates of acquisition of the active avoidance response than did 2-month-old rats. In addition, the retention of the active avoidance response in 6- and 12-month-old rats diminished rather rapidly compared with that observed in 2-month-old rats. Intraventricular injection of acetylcholine at doses of 20 and 50 ng caused a significant improvement of memory impairment in old rats. Physostigmine and arecoline also caused a significant ameliorating effect at doses of 0.02 and 0.05 mg/kg i.p. and 0.2 and 0.5 mg/kg i.p., respectively. Hopantenate calcium (100 mg/kg, p.o.), idebenone (20 and 50 mg/kg, i.p.), indeloxazine (50 mg/kg, p.o.) and DM-9384 (30 mg/kg, p.o.) also proved useful to improve memory impairment in old rats. PMID- 2098551 TI - Tritium concentration in Japanese rice. AB - Polished rice samples harvested in 1985 were collected from 25 prefectures throughout Japan. Concentrations of both tissue free water tritium (TFWT) and organically bound tritium (OBT) were determined. Nearly uniform distribution of the TFWT and OBT concentrations was observed in Japan, taking into account a relatively large counting error. The average values for all Japanese polished rice were 2.69 +/- 0.74 Bq/L for the TFWT concentration, 2.01 +/- 0.78 Bq/L for the OBT concentration and 0.83 +/- 0.32 for the specific activity ratio. The TFWT concentration was within the range of tritium concentration of the land water reported by other researchers. The specific activity ratio below unity also confirmed by analyses of the 4 Chinese polished rice samples suggests that OBT in the rice is not equilibrated with TFWT or HTO in the environment because of isotope discrimination. PMID- 2098553 TI - Water content in cultured mammalian cells for dosimetry of beta-rays from tritiated water. AB - One of the critical factors for dosimetry of beta-rays from tritiated water is the water content within the cell. We estimated the cellular water concentration in cultured mammalian cells by measuring accurately the fraction of the extracellular water in the cell sample with [14C]inulin. The net water content (ml.g-1) after correcting for the extra-cellular water fraction was 0.858 for HeLa (human), 0.833 for JTC12P3 (monkey), 0.829 for NRK (rat), 0.843 for C3H10T1/2 (mouse) and 0.846 for L5178Y (mouse) cells. The mean water content (+/- S.E.M.) in these 5 lines of cultured mammalian cells was 0.842 +/- 0.005. PMID- 2098552 TI - Radiosensitivity of macrophage colony-forming cells-implications for their heterogeneity. AB - We compared the radiosensitivity of macrophage (M) colony-forming cell (CFC) in and outside the hemopoietic bone marrow. Murine bone marrow cells (BMC) are stimulated by either macrophage colony-stimulating factor (CSF-1) or murine recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) to form M- and granulocyte- macrophage (GM) colonies on soft agarose medium, whereas both peritoneal exudate cells (PEC) and pulmonary alveolar macrophages (PAM) also have a capacity to make only M- colonies either by rGM-CSF or CSF-1. The clonal growth of peritoneal exudate CFC (PE-CFC) and alveolar macrophage CFC (AL-CFC) was more effectively achieved with rGM-CSF, and their cloning efficiencies were much higher than bone marrow CFC (BM-CFC). Following in vitro exposures to gamma irradiation (1Gy/min), the dose-survival response of each M-CFC grown by cultures with either rGM-CSF or CSF-1 indicates that the radiosensitivity was the highest in BM-CFC, whereas Al-CFC was more radioresistant than PE-CFC. Surface antigen expression, such as macrophage-specific F4/80, on these CFCs, was invariable before or after irradiation except that it was diminished on irradiated PE-CFC. These results indicate the heterogeneity of tissue M-CFCs in their radiosensitivities as well as in responsiveness to CSFs. PMID- 2098554 TI - Neutron and gamma-irradiation of bacteriophage M13 DNA: use of standard neutron irradiation facility (SNIF). AB - We describe here the use of the Van de Graaff accelerator as a source of high energy neutrons for biological irradiation. Single-stranded bacteriophage M13 DNA was chosen as the system to determine the relative biological effectiveness of monoenergetic neutrons. A Standard Neutron Irradiation Facility (SNIF) was established using a 3 MV Van de Graaff accelerator. The 2D (d,n)3He nuclear reaction was used to produce neutron fluxes of 3 x 10(8) cm 2 sec-1 yielding dose rates as high as 50 Gy h-1. A detailed description of the neutron source, neutron fluence measurement, dose calculation and calibration are included. Exposure of single-stranded bacteriophage M13 DNA to 90 Gy of neutrons reduced survival to 0.18% of the unirradiated value. 500 Gy of gamma-rays were required for the same level of killing, and RBE was estimated at 6 based on Do values. Determination of the extent of DNA damage after exposure to cleavage using gel electrophoresis, gave RBE values of 6-8 which was very similar to that observed for bacteriophage survival. The facility described here provides a reproducible source of high energy monoenergetic neutrons and dose levels suitable for experiments designed to measure DNA damage and effects on DNA synthesis. PMID- 2098555 TI - Effect of "in utero" exposure to low doses of low energy X-rays on the postnatal development of mouse. AB - Pregnant Swiss albino mice were exposed to a single dose of 9 mGy or 50 mGy of 70 kVp X-rays on day 3.5 (preimplantation), 6.5 (early organogenesis) or 11.5 (late organogenesis) of gestation. The offspring were observed for any radiation induced changes in litter size at birth and sex ratio at 4 wks of age, and postnatal mortality and growth retardation up to 6 wks of age. Irradiation at the early organogenesis stage produced an increase in the postnatal death, statistically significant in the 50 mGy group. A significant increase in the number of retarded offspring and decrease in body weight were observed in the groups exposed at the early and late organogenesis periods. The results indicate that a single exposure to low energy low dose X-rays can be harmful to the growing embryos and the type and extent of the injury will depend on the stage of development as well as the dose of radiation. PMID- 2098556 TI - Biological assessment of the enhancement of tritium excretion by administration of diuretics and excessive water in mice. AB - This study was undertaken to determine whether or not the administration of diuretics and excess water after tritium exposure would have any positive reducing effect not only on the retention of tritium but also on the radiation damage of hematopoietic tissue in mice. When mice were treated with diuretics and excess water for a few days after injection of tritiated water (HTO), radioactivity within the body fluid and tissues was reduced, and the number of CFU-s, clonability of splenic T cells and proliferative activity assayed by Con-A blastogenesis were increased in comparison with those in the controls. When the mice were injected with a large dose of HTO (811 MBq/mouse) to assay survival, no mice treated with diuretic and excess water died 80 days after injection, while 80% of the controls died during the first month. The final committed dose in the mice treated early with diuretics was calculated to be 60% of that in the controls. These results suggest that treatment with diuretics and excess water is useful for practical purposes when a human is accidentally exposed to tritium. PMID- 2098557 TI - Effects of Z-100 on mice exposed to gamma-irradiation: a preliminary report. AB - Subcutaneous administration of Z-100 twice a week starting immediately after supralethal whole-body irradiation of mice produced a prolongation of survival time. The effect of Z-100 on the hematopoietic system was thought to have contributed to the prolongation and was thus investigated. A single subcutaneous dose of Z-100 immediately after irradiation inhibited reduction of the total number of nucleated cells in the femoral bone marrow of the treated mice, although the inhibition was not by promotion of the proliferation of specific cells but by promotion of the recovery of multiple cell lines. Treatment with Z 100 promoted colony formation in the spleen of the treated mice and CFU-S formation in the femoral bone marrow, indicating that the drug accelerated the recovery of hematopoietic stem cells. The recovery of CFU-C count was also promoted by Z-100, which suggested that the drug has a restoring effect on the recovery of granulocytic and macrophagic precursor cells. Furthermore, Z-100 produced a greater increase in the CSF activity in the serum of irradiated mice, leading to the presumption that CSF induced by Z-100 was greatly involved in promoting the recovery of the above-mentioned hematopoietic stem cells. We conclude that Z-100 prolonged survival time of irradiated mice by promoting recovery of hematopoiesis of the mice. PMID- 2098558 TI - Development of nonthymic lymphomas in thymectomized NFS mice exposed to split dose X-irradiation. AB - Split-dose X-irradiation efficiently induced Thy-1-positive thymic lymphomas (80%) in intact NFS mice within 12 months after irradiation. A high incidence (67%) of nonthymic lymphomas and leukemias was observed in the thymectomized NFS mice. Development of nonthymic lymphomas and leukemias in these mice started about 2 months later than that of thymic lymphomas and increased significantly 10 months onward after the last irradiation, when the development of thymic lymphomas in intact mice had already come to an end. These nonthymic lymphomas and leukemias involved predominantly the spleen and the mesenteric lymph nodes. Twelve out of 18 lymphomas and leukemias were examined immunocytologically. All of these tumors except one were diagnosed as lymphomas including one plasmacytoma. One case was diagnosed as myelomonocytic leukemia because the leukemic cells were highly positive for nonspecific esterase and negative for chrolacetate esterase. All lymphomas tested were negative for thy-1.2, and five of them expressed surface immunoglobulins. From these results, nonthymic lymphomas developed in thymectomized and X-irradiated NFS mice were classified as B-cell lymphomas probably including non-T/non-B cell lymphomas. Present findings demonstrated that a low incidence of nonthymic lymphomas in intact NFS mice exposed to split-dose X-irradiation should be ascribed to a longer latency since most of the mice died of thymic lymphomas prior to the development of overt nonthymic lymphomas. PMID- 2098559 TI - Radiation absorbed from dental implant radiography: a comparison of linear tomography, CT scan, and panoramic and intra-oral techniques. AB - Absorbed radiation dose in bone marrow, thyroid, salivary gland, eye, and skin entrance was determined by placement of lithium fluoride thermoluminescent dosimeters (TLD's) at selected anatomical sites within and on a human-like x-ray phantom. The phantom was exposed to radiation from linear tomographic and computer-assisted tomographic (CT) simulated dental implant radiographic examinations. The mean dose was determined for each anatomical site. Resulting dose measurements from linear tomography and computer-assisted tomography are compared with reported panoramic and intra-oral doses. CT examination delivered the greatest dose, while linear tomography was generally lowest. Panoramic and intra-oral doses were similar to those of linear tomography. PMID- 2098560 TI - Establishment of an implant selection protocol for predetermined success. AB - Previously, implant selection was confined to radiographs and to plastic implant templates for evaluation of existing bone. The aim of this study was to determine implant support areas in a compressive mode and to establish a standard via an implant selection protocol. Successful implant selection, regardless of the device design, is relevant to a patient's muscular efficiency and implant support values based on bone quality and size of prescribed bridge. The compressive areas of support, in mm2, of 15 implant designs were computer-analyzed and graph evaluated. Major/minor diameters and the lengths of screws and cylindrical types of devices were calculated. In addition, the length, width, vents, and any lateral support areas of blade types were recorded. Average muscular force data, provided by clinical transducer studies, and literature reports of the mechanical properties of trabecular bone were correlated with computer bone analyses. These studies determined the quality of maxillary and mandibular bone to be 10 MPa and 15 MPa, respectively. Results indicated that four-unit bridges, at 50 lbs of applied force, require an area 31.14 mm2 of implant support in a compressive mode in the maxilla, and a support area of 20.76 mm2 in the mandible. Five-unit bridges require 40.84 mm2 in the maxilla and 27.23 mm2 for the mandible, because of the moment force, or torque, on the implant. Findings indicated that by determining: (1) the patient's muscular efficiency at implant sites (quantifying dynamic values of the forces and moments on implants supporting functioning bridges); (2) implant support values based on the compressive strength of the cancellous bone at implant sites; and (3) the size of the prescribed bridge, it is possible for the success (or failure) of a selected implant to be predetermined. PMID- 2098561 TI - Report of the incidence of implant insert fracture and repair of Core-Vent dental implants. AB - This is a report of the fracture of Core-Vent 2.0-mm-O.D. cementable abutments. A technique for removal and replacement of these inserts is described, which enables the clinician to retain the original mesostructure bar. PMID- 2098562 TI - Suspension mechanism of subperiosteal implants in baboons. AB - It has been noted that overloading of an implant can lead to the premature loss of implants (Jones et al., 1979; Travis and Jones, 1986). An understanding of the mechanism by which subperiosteal implants support masticatory loads could lead to appropriate design changes for best utilization of this mechanism and thus increase the predictability of subperiosteal implants (James, 1983). This study attempts to analyze the suspension mechanism in implants recovered from a baboon after 10 years' use. PMID- 2098563 TI - Maxillary sinus: anatomy, physiology, surgery, and bone grafting related to implantology--eleven years of surgical experience (1979-1990). AB - The sinus is a pneumatic cavity of the facial skeleton within maxillary bone. It is very closely linked to the alveolar crest, the resorption of which, especially when tooth loss occurs, could cause a serious obstacle to oral implantology. It is therefore of great importance for this obstacle to be removed by adequate surgical procedures aimed at reducing the expanded volume of this cavity either partially or totally. Several grafting techniques involving autogenous bone (either alone, mixed with a bone-substituting biomaterial, or with insertion of only a biomaterial) are now available. The biomaterials include an increasing variety of treated bone from a bone bank. This paper will endeavor to outline the basic scientific and clinical knowledge required for this important surgery and will also stress the grave dangers that lie behind complications that may result from the inadequate practice of surgery by untrained operators. PMID- 2098564 TI - Challenges for technology transfer of implant dentistry: research and educational issues for the 1990's. PMID- 2098565 TI - Clinical trials for implant dentistry: why not? PMID- 2098566 TI - The state of the science of patient outcome research. PMID- 2098567 TI - Reactors' comments: NIDR perspectives on implantology research. PMID- 2098568 TI - Toronto experience. PMID- 2098569 TI - Harvard experience. PMID- 2098570 TI - Regulatory and biomaterials investigations. PMID- 2098571 TI - General discussion. PMID- 2098572 TI - Immediate loading of cylinder implants with overdentures in the mandibular symphysis: the titanium plasma-sprayed screw technique. AB - A technique is described for the placement of titanium plasma-sprayed screw implants in the mandibular symphysis. Four TPS screw implants are placed in the mandibular symphysis. An impression is made for a meso-bar at the time of surgery, and a bar is placed four to seven days following the surgery. A soft re lined denture is placed over the bar as a provisional prosthesis during the initial healing phase following implant placement. The surgical and prosthetic management of implant-supported overdenture cases may be greatly simplified with the use of this technique in a carefully selected group of patients. Additionally, patients experience improved function during the initial healing phase following implant placement. A review of the literature indicates that osseo-integration is achieved with a high level of predictability (Buser et al., 1988) when this technique is properly applied. PMID- 2098574 TI - Academics and education. PMID- 2098573 TI - Assessment of adjunctive flurbiprofen therapy in root-form implant healing with digital subtraction radiography. AB - The goals of these case reports were to (1) apply digital subtraction radiography to the assessment of the healing of root-form implants so that small changes in bone height and density could be detected and (2) to compare the bony support around root-form implants in patients prescribed the non-steroidal anti inflammatory drug, flurbiprofen, with support in patients who did not receive the flurbiprofen as adjunctive therapy. Titanium root-form implants were surgically placed in four patients who were randomly assigned to receive either 100 mg flurbiprofen twice a day for three months or no flurbiprofen (as controls). Radiographs were taken immediately post-operatively and at four months. Digital subtraction radiography was used to detect sites of bone gain, loss, or unchanged bone around the implant. This four-month pilot study suggests that the non steroidal anti-inflammatory drug, flurbiprofen, appears to be associated with increased bone density surrounding dental implants, and that digital subtraction radiography may be useful for the evaluation of bone density changes around dental implants. PMID- 2098575 TI - New distance system for the submersible use of the ITI-BONEFIT implants. PMID- 2098576 TI - A study on content and distribution of plasma and tissue fibronectin in rats using ELISA and immunofluorescence. AB - The content of plasma fibronectin and tissue extractable fibronectin in normal rats was measured with rocket immunoelectrophoresis and ELISA in the present study. The difference in tissue fibronectin distribution in various organs and the correlation between distribution and content of fibronectin have been studied. We suggest that tissue fibronectin may be a complex component. The change in plasma fibronectin reflects a dynamic balance existing between the tissue fibronectin pool and plasma fibronectin pool in normal rats. Plasma fibronectin and tissue fibronectin concentrations are not static, and they can only be maintained in a relatively stable state in normal rats. PMID- 2098577 TI - [Total femur and hip knee joint replacement with plasma-sprayed ceramic coated prosthesis]. AB - A method of prosthetic replacement using total femur with total hip and knee joints is reported. On the surface of the titanium endoprosthesis a ceramic coating was plasma-sprayed to prevent loosening of the prosthesis. By this method the limb can be preserved and the function restored within a short period. It can be used in certain cases of non-malignant tumors and diseases of the bone with extensive destructive lesions of the entire femur. This method was used on 3 patients with good results. The patients operated on were followed up for 32-70 (mean 54) months. The procedures and advantages of the operation are presented. PMID- 2098578 TI - The first case of Pseudallescheria boydii meningitis in China--electron microscopic study and antigenicity analysis of the agent. AB - Reported in this paper is the first case of isolation of Pseudallescheria boydii from cerebral spinal fluid of a boy with meningitis in China. Morphology and culture were observed by light microscopy, electron scanning microscopy and transmission electron microscopy. In addition, mycelium antigen prepared by SDS PAGE was compared with that of the other strain of Scedosporium apiospermum. Both of the strains showed more than 40 peptide lines. Their molecular weight was very similar. On the CS-930 Dual-Wavelength TLC Scanner the peaks of both antigens showed to lie in nearly the same position. It could be concluded that Pseudallescheria boydii and Scedosporium apiospermum belong to the same genus, but they are of different strains and reproductive phases. PMID- 2098580 TI - Preliminary study of quantification of regurgitant volume in mitral regurgitation by color Doppler echocardiography. AB - A method for quantification of regurgitant volume in mitral regurgitation (MR) was studied. 31 cases of MR were investigated with color Doppler. The reliability of measuring velocity by Doppler and the influence of pressure gradient on MR were assessed and confirmed by experimental device. The results suggested that the best method in quantification of the regurgitant volume was "calibrating method" (r = 0.99; P less than 0.01), the next to the best was "volume method" (r = 0.74; P less than 0.01), whereas the regurgitant volume evaluated by multiplication of area, velocity and time was far from the actual regurgitant volume (r = 0.47; P greater than 0.05). The velocity of blood flow measured by Doppler is closely correlated to results obtained from experiments (r = 0.69; P less than 0.05). We believe that the ratio of back flow area and average area of left atrium calculated by Helmcke's method reflects the severity of the disease to a certain degree, bu there are many problems unsolved, e.g. the determination of the velocity of blood flow by color Doppler is dependent on the degree of brightness of coloration; the brighter the color, the quicker the speed it represents, whereas the darker coloration speaks for slower speed. PMID- 2098579 TI - [Influence of surgical intervention on the course of patients with rheumatic mitral valvular defects]. AB - A retrospective study of 798 patients from Essen University Medical Hospital during the period 1960-1987 with operation performed due to valvular heart disease was undertaken. Among them were 324 suffering from mitral stenosis, 12 from mitral regurgitation, 462 from mixed mitral valvular diseases. The surgical treatment consisted of commissurotomy in 611 patients, and prosthetic valve replacement in 187 patients. Follow-up studies showed: Before and after operation, occurrence of embolism was 16.5 vs 8.7%; status of class of cardiac function (NYHA) from group with commissurotomy was 3.1 vs 2.0; NYHA classification in group of prosthetic replacement was 3.1 vs 1.9; 10 years survival rate after commissurotomy was 95.2%; after valve replacement it was 80.2%; early letality rate after operation (at or within 2 months after operation) depended on 1) the type of operation: commissurotomy 2.8%, valve replacement 10.2%; 2) the state of cardiac function: in class IV it was 12.9%, in class III 4.6%; 3) the number of operations: in only operation it was 4.8%, in reoperations 19.5%. Thus the following fact will lead to false judgement: though the area is the same, the regurgitant volume may vary with the brightness of coloration. Furthermore the left auricle will be enlarged consequently following the increase of regurgitant volume, also causing misinterpretation. It is of practical importance to consider some other factors in quantifying the regurgitant volume. PMID- 2098581 TI - Experimental and clinical studies on inhibitory effect of ganoderma lucidum on platelet aggregation. AB - In this study we observed the inhibitory effect of Chinese herbal medicine Ganoderma lucidum (GL) on platelet aggregation in 15 healthy volunteers and 33 patients with atherosclerotic diseases. The results showed that the first and the second phase of aggregation of platelets of the healthy volunteers were obviously inhibited (P less than 0.01) when watery soluble extract of GL of different concentrations was added to the platelets in vitro, i. e., the reaction speed of platelet aggregation was slowed down. The inhibitory effect was related to dosage. Platelet aggregation induced by ADP in final concentration of 2 mumol/L and 3 mumol/L was obviously inhibited, after the patients had taken GL 1 g 3 times a day for 2 weeks, the maximum platelet aggregation inhibition rates were then 31.49% (P less than 0.01) and 17.7% (P less than 0.01) respectively. Length and weights (wet and dry) of the extracorporeal thrombi were reduced from 30.05 +/- 4.38 mm, 103.9 +/- 9.33 mg and 44.89 +/- 4.79 mg to 20.4 +/- 2.33 mm (P less than 0.05), 85.27 +/- 8.77 mg (P less than 0.01) and 35.1 +/- 4.5 mg (P less than 0.01) respectively after oral administration of GL. The results of our experiments suggested that the Chinese herbal medicine GL may be an effective inhibitory agent of platelet aggregation. However, its mechanism and active principles remain to be further investigated. PMID- 2098582 TI - Segmental fixation with U-shaped rod in the treatment of spondylolisthesis. AB - From 1987 to 1990 the authors treated 20 cases of spondylolisthesis by an improved operative procedure including excision of the medial part of the superior articular processes of the slipped vertebra, excision of the soft tissue between the ununited isthmi, and excision of the ligamentum flavum between the intervertebral space above the slipped segment. In some instances the lower portion of the lamina over the slipped vertebra should be resected. A U-shaped rod was used to hold sublaminar fixation of two segments above and below the slipped vertebra, with the slipped vertebra spared. Utilizing the U-shaped rod as support, bone strips were placed along the lateral and anterior sides of the rod to bridge the gap between the laminae of the displaced vertebra. Other bone grafts were focused on the facet joints. The patients were allowed ambulation early postoperatively. 19 cases could be evaluated at preliminary follow-up. All showed satisfactory results. PMID- 2098583 TI - Comparison of effects of magnesium valproate and sodium valproate on the action potential of isolated papillary muscle from guinea pigs and dogs. AB - A comparison of the effects of magnesium valproate (MV) and sodium valproate (SV) on the action potential of isolated papillary muscle from guinea pigs and dogs was made in this study. The results in both animals were as follows: MV and SV induced a slight reduction of slope plateau of action potential and prolongation of action potential duration (APD). What is more, APD50 and APD90 were prolonged significantly, thus the ratio of APD90/APD25 was increased. The effective refractory period (ERP) was prolonged significantly. MV or SV showed no effects on action potential amplitude, overshoot, resting potential and phase 0 upstroke velocity. The above results suggested that MV and SV might play an antiarrhythmic role and that their effects were analogic. The mechanism of MV and SV inducing significant prolongation of APD50, APD90, and ERP, might be closely related to the slow-down of the velocity of K+ efflux during plateau and repolarization of phase 3 by radical of valproate and the slow-down of velocity of K+ efflux of repolarization of phase 3 in particular. These results showed that there was no difference in SV and MV action on guinea pigs and dogs. PMID- 2098584 TI - Determination of trace selenium in human body by anodic stripping voltammetry at gold-disc electrode. AB - For determination of trace Se we used high-pressure wet digester to pretreat the specimens obtained from the human body. This method is very effective in preventing loss of Se by volatilization which often occurs in the sample pretreatment. We studied the method of using anodic stripping voltammetry at gold disc electrode to measure the trace Se present in the human body and found it to be the optimal procedure. The detection limitation was about 2 x 10(-8) g/L, the recovery rate of Se about 96.6 +/- 6.7% (chi +/- s), and the coefficient of variation CV = 7.0%. PMID- 2098585 TI - [Changes in systemic circulation under induced total spinal block and choice of vasopressors]. AB - Total spinal block by using 2% lidocaine 0.5 ml.kg-1 (10.0 mg.kg-1) was carried out in adult mongrel dogs. The effects of atropine 0.02 mg.kg-1, isoproterenol 0.5 mcg.kg-1, methoxamine 0.1 mg.kg-1 and ephedrine 0.5 mg.kg-1 to counteract circulatory changes by total spinal block were studied. Atropine did not exert any marked influence on circulatory system. Isoproterenol elevated HR, LV dp/dt max and CI temporarily, but did not decrease MAP and SVR. Methoxamine elevated MAP and SVR, but decreased CI. Ephedrine is a drug of choice for this situation because it elevated HR, MAP, LV dp/dt max and SVR. PMID- 2098586 TI - [Hemodynamic features of hypotension induced by nicardipine in dogs]. AB - Hemodynamic features of hypotension induced by nicardipine were studied in 18 mongrel dogs under 0.87% halothane in oxygen (1MAC). They were randomly allocated to one of two groups. Group C received no vasodilator therapy and served as control and group N received infusion of nicardipine. Mean arterial pressure decreased and was maintained at 60 mmHg for 60 minutes in group N. No change was noted in hemodynamic variables measured in group C throughout the experiment. During and after induced hypotension in group N, cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP), and right ventricular stroke work index (RVSWI) increased significantly compared with the control values. On the other hand, systemic vascular resistance (SVR) was significantly reduced, reaching 25% of the control value at the end of hypotension period. Heart rate showed a progressive increase but not significantly. Left ventricular maximum dp/dt showed a moderate increase during hypotension, but then decreased gradually to the control value after induced hypotension. Left ventricular stroke work index (LVSWI) and pulmonary vascular resistant (PVR) were unchanged from the control value during and after induced hypotension. The data indicate that nicardipine is a potent systemic vasodilator with hyperdynamic hemodynamic effects in addition to significant increase in right ventricular function. PMID- 2098587 TI - [The evaluation of tracheal temperature to monitor core temperature in various operations]. AB - Tracheal temperature was evaluated to monitor core temperature during cardiac, upper abdominal and lower abdominal operations. The tracheal temperature was measured by a thermistor attached to the intra-cuff of the tracheal tube. In cardiac surgery, there was a good correlation between tracheal temperature and forehead deep temperature (r = 0.93) before and after cardiopulmonary bypass, and also between tracheal temperature and the temperature of blood from the cardiopulmonary bypass (r = 1.00) during cardiopulmonary bypass. These results indicate that tracheal temperature accurately reflects carotid artery temperature. In upper abdominal operations, the tracheal temperature showed good correlations with forehead core, esophageal, bladder and rectal temperatures (r = 0.81-0.90). On the other hand, bladder and rectal temperatures were different from forehead deep (r = 0.43, 0.55) and tracheal temperatures in lower abdominal operations. These results suggest that the tracheal temperature is valuable to monitor core temperature. PMID- 2098588 TI - [Comparison of effects of intravenous versus intramuscular famotidine on pH and volume of gastric juice]. AB - Famotidine, an H2-antagonist, is frequently used for prevention of acid aspiration in surgical patients. Intravenous as well as intramuscular administration of famotidine has proved effective to reduce gastric acid secretion during anesthesia. However, the onset and duration of action of famotidine following intravenous administration has not been extensively investigated. In the present study on 89 patients undergoing elective surgery, the effects of famotidine 20 mg administered intravenously 5-30 min before endotracheal intubation on pH and volume of gastric contents aspirated 0, 1, 2, and 4 hrs after tracheal intubation and immediately after extubation through nasogastric tube were compared with the effects of the drug administered intramuscularly one hour before endotracheal intubation. Famotidine administered intramuscularly 5-14 min before endotracheal intubation produced inadequate suppression of gastric secretion after tracheal intubation. In contrast, intravenous famotidine given 15-30 min before tracheal intubation, as well as the intramuscular administration of famotidine as premedication, effectively decreased gastric fluid volume and increased gastric pH. Suppression of gastric secretion by intravenous and intramuscular famotidine continued for over 4 hours. Intravenous famotidine has a rapid onset and a long duration of depressant action on gastric secretion, thus reducing the risk of aspiration pneumonitis during and after general anesthesia. PMID- 2098589 TI - [Effect of continuous epidural infusion of morphine on postoperative glucose metabolism]. AB - Plasma growth hormone (GH), insulin, prolactin and blood glucose levels were measured to evaluate postoperative pain relief either with epidural morphine or systemic analgesics in 16 patients who underwent gastrectomy. Continuous epidural morphine with a pump (CADD-PCA, Model 5200P, Pharmacia) was given to eight (epidural morphine group) patients. A bolus of epidural morphine was administered through an indwelling thoracic (Th8.9) catheter at 3 hrs prior to the expected end of surgery, which was followed with continuous epidural infusion of morphine at a rate of 0.167-0.042 mg.hr-1 with the pump during and after anesthesia and surgery with gradually decreasing dose until the third postoperative day. The remaining eight patients (systemic analgesics group) repeatedly received intravenous or intramuscular pentazocine and buprenorphine when needed. Plasma GH levels increased significantly only on the first postoperative day in both groups. Plasma insulin levels increased significantly on the first postoperative day in both groups. Blood glucose levels increased significantly at the end of surgery and during the following three postoperative days in both groups. There are no statistical differences in plasma GH, insulin and blood glucose levels between the two groups. Plasma prolactin concentrations increased significantly at the end of surgery and they were significantly higher in the systemic analgesic group than in the epidural morphine group. They, however, returned to the previous day's levels on the first postoperative day in both groups. Our study suggests that continuous epidural infusion of morphine has no suppressing effect on postoperative changes in plasma GH, insulin, prolactin and blood glucose levels as compared with systemic analgesic regimen. PMID- 2098590 TI - [Effects of prostaglandin E1 on cerebral blood flow, cerebrospinal fluid pressure, and spinal subarachnoidal compliance]. AB - In enflurane-anesthetized subjects, controlled hypotension was induced by the intravenous administration of prostaglandin E1 (PGE1), and its effects on the cerebral blood flow (CBF) and intracranial pressure (ICP) were investigated by using changes in the flow velocity of the ophthalmic artery (OPA) and cerebrospinal fluid pressure (CSFP) as indices, respectively. After measurements of these hemodynamic variables, the spinal subarachnoidal compliance was also determined, and its relationship with the flow velocity in the ophthalmic artery and CSFP was investigated. The results of the study suggest that PGE1 causes no significant changes in CSFP and that cerebral blood flow is well-maintained despite a reduction in cerebral perfusion pressure. PMID- 2098591 TI - [Hypothermia after cardiopulmonary bypass in man: effects of prostaglandin E1 and phentolamine]. AB - The "afterdrop" in body temperature (TEMP) following adequate rewarming from hypothermic cardiopulmonary bypass (CPB) is frequently observed. This temperature drop sometimes accompanied by shivering results in increased myocardial oxygen demand. We investigated the relations between the afterdrop and use of vasodilators after CPB. For vasodilator therapy, PGE1 at the rate of 0.025-0.088 microgram.kg-1.min-1 (Prostaglandin Low Doses, PLD; n = 8), 0.107-0.136 microgram.kg-1.min-1 (Prostaglandin High Doses, PHD; n = 7), or phentolamine at 4.1-5.9 micrograms.kg-1.min-1 (PHENT; n = 8) were intravenously infused in 23 adult patients after CPB. During three hour period after CPB, esophageal, rectal, and forehead TEMP are lower in PHENT than in PGE1 groups. There were significant differences between PHD and PHENT group. Finger tip TEMP was lower in PGE1 groups than in PHENT group. There were significant differences between PHD and PHENT group. There were no differences in systemic arterial pressure, cardiac index (CI) and systemic vascular resistance (SVR) at any point between PHD and PHENT groups. It is concluded that PHENT increases the peripheral skin blood flow and TEMP but decreases the visceral TEMP possibly due to vasodilatation of the skin vessels, while PGE1 decreases skin blood flow and TEMP but increases the visceral TEMP, although SVR clearly decreases at the same rate in the two groups. PMID- 2098592 TI - [The effect of xanthine oxidase inhibitor on hindlimb ischemia-induced thromboxane A2 release]. AB - Our previous studies demonstrated that the bilateral hindlimb ischemia/reperfusion stimulates thromboxane A2 (TXA2) production. The present study tests the role of xanthine oxidase-derived oxygen free radicals in mediating this event. In twelve anesthetized dogs, the abdominal aorta and the inferior vena cava were clamped for 150 min, declamped and reperfused for 30 min. Two groups were studied: untreated control group and pretreated group with xanthine oxidase inhibitor, allopurinol 100 mg.kg-1 orally 24 hr before clamping plus 25 mg.kg-1 intravenously 15 min before clamping. In the control group, plasma TXB2 levels increased markedly after reperfusion. On the other hand, prior treatment with allopurinol attenuated the increase in plasma TXB2 levels at 30 min after reperfusion. This model revealed partial ischemia, because the femoral arterial blood flow was approximately 15% of baseline during clamping. However, the present study suggests that ischemia/reperfusion stimulates TXA2 production, which may be partly affected by hypoxanthine-xanthine oxidase-derived oxygen free radicals and may be an important mechanism responsible for reperfusion injury. PMID- 2098593 TI - [The effect of ketamine on epinephrine-induced arrhythmias in dogs anesthetized with halothane-nitrous oxide]. AB - The effect of ketamine on the arrhythmogenic dose of epinephrine (ADE) was studied in dogs anesthetized with halothane-nitrous oxide. Groups K (ketamine 2, 4, 6, 10, 20 mg.kg-1.hr-1) were compared with group C (only halothane-nitrous oxide), and the ADE in group K2, 10 was significantly lower than that in group C. The arrhythmogenicity of ketamine was not found in group K20. There was a significant correlation between % ADE (ADE in group K/ADE in group C X 100) and plasma ketamine levels. However, antiarrhythmic action of ketamine was found following intravenous injection of ketamine 6 mg.kg-1, when plasma ketamine level was 14.3 +/- 1.9 micrograms.ml-1. Ketamine was cardiovascular depressant at high concentration, and this effect could account in part for the antiarrhythmic action of ketamine in this condition. The ketamine inhibited adrenal catecholamine secretion, but plasma epinephrine level in group K4 was higher than that in group C when the same dose of epinephrine was infused. Therefore the inhibition of neuronal and extraneuronal catecholamine uptake by ketamine would offer an explanation for the augmentation of response to epinephrine. Then, this augmentation would cause the arrhythmogenic action of ketamine. PMID- 2098594 TI - [Clinical evaluation of isosorbide dinitrate (ISDN) spray: a study on the plasma concentrations of ISDN and on its hemodynamic effects using three administration routes]. AB - The effects of ISDN spray has been evaluated using oral, nasal or tracheal routes in patients under enflurane anesthesia. These 30 patients were in ASA I or II physical status without cardiovascular, kidney or liver diseases. Under enflurane anesthesia, hemodynamic parameters (blood pressure and heart rate), blood gas and plasma concentration of ISDN were measured at several points before and after drug administration. The plasma concentration reached a maximum point (C max) 4 min after drug administration in the oral group (O-group) and nasal group (N group), and the values obtained were 48.4 +/- 5.4 ng.ml-1 and 87.4 +/- 13.8 ng.ml 1 respectively. The C max of the N-group was significantly higher than that of O group (P less than 0.05). In the O- and N-groups, systolic blood pressure decreased 10% and 17%, after 4 min (P less than 0.05) and recovered 20 after min. Diastolic blood pressure decreased in both groups after 4 min (P less than 0.05). Heart rate significantly increased in the N-group (P less than 0.05), and continued to change up to 60 min after drug administration. In both groups, PaO2/FIO2 decreased 14% and 9% after 10 min (P less than 0.01). In the tracheal group, plasma concentration did not increase and these hemodynamic changes were not observed. These results suggest that nasal route of ISDN spray is the best route of administration. PMID- 2098595 TI - [Effect of midazolam as a premedicant]. AB - A new benzodiazepine-type drug, midazolam, was administered intramuscularly as a premedicant to 155 patients aged from 16 to 81 years with ASA status 1 or 2. The hypnotic action and the effect on the upper airway tract of midazolam were evaluated. Hypnosis appeared 5 minutes after the administration of midazolam, reached its plateau after 20 minutes and started to decline after 30 minutes. The hypnotic effect showed dose-dependent increase in doses ranging from 0.05 to 0.20 mg.kg-1. No age-dependent differences in hypnosis were observed except for teenage group which showed stronger hypnosis than the other age groups. There was no problem on the upper airway tract for all age groups at the dosage of 0.05 mg.kg-1, but in the patients over 40 years increasing dosage tended to obstruct the upper airway tract. Along with the appearance of hypnosis, cough and breath holding, suggesting retention and aspiration of saliva, were observed. The appropriate dosage of midazolam for premedication was considered to be 0.05 mg.kg 1. PMID- 2098596 TI - [Clinical evaluation of midazolam as an anesthetic for geriatric patients and patients with hepatic dysfunction]. AB - This study evaluated the usefulness of midazolam in inducing a anesthetic state in 60 patients who underwent surgery under general anesthesia. The patients were divided into 3 groups; a geriatric group, a hepatic dysfunction group, and a control group (adults without complications). To induce sleep 0.15 mg.kg-1 or 0.2 mg.kg-1 of midazolam was administered intravenously to all three groups. After the administration of midazolam, the mean time for obtaining absence of response to calling name and absence of ciliary reflex were not significantly different in the three groups. The pulse rate and respiratory rate also did not change remarkably. But significant decreases were observed in the systolic blood pressure and tidal volume in all three groups. However, they were not significantly different among the three groups. These results indicate that midazolam is a useful drug for inducing anesthetic state in geriatric patients and patients with hepatic dysfunction. PMID- 2098597 TI - [Preoperative aspects of blood rheology in patients who developed multiple organ failure following cardiac surgery]. AB - The relationship between preoperative hemorheology and postoperative course was studied in 38 patients who had undergone open heart surgery for valvular diseases (mean age, 53 +/- 2 S.E. years). Twelve patients had multiple organ failures (MOF) one week after surgery, while the remaining 26 patients were in satisfactory condition. The hematocrit (Ht) was 34.8 +/- 1.6 S.E.% in patients with MOF and it was 40.4 +/- 0.9 S.E.% in patients without MOF. The difference was significant. Blood viscosities (eta) at shear rates of 94.5 sec-1 and 0.376 sec-1 also were significantly lower in patients with MOF compared with those without MOF. However, oxygen delivery (Ht/eta at a shear rate of 94.5 sec-1) in terms of hemorheology, plasma viscosity, and erythrocyte deformability were not significantly different between the two groups. These data suggest that patients with a low hematocrit and a low viscosity are likely to suffer from MOF following surgery. PMID- 2098598 TI - [Anesthetic management of hypothyroid patients for coronary artery bypass grafting]. AB - Six hypothyroid patients with ischemic heart disease underwent coronary artery bypass grafting (CABG). Three of them were in euthyroid state by preoperative thyroid supplementation. Although remaining three who had not received preoperative supplementation were in overt hypothyroid state at CABG, their intra and postoperative courses were satisfactory without any complications. We, therefore, found no benefit from preoperative thyroid supplementation. Serum TSH levels in hypothyroid patients were suppressed for more than three days postoperatively despite concomitant low FT3 and FT4 concentrations. The inhibition of TSH secretion could have been produced by therapeutic dose of dopamine which had been infused from intraoperative through postoperative period. Postoperative thyroid replacement should be initiated as soon as possible in hypothyroid patients to counteract the low FT4 concentration that could be prolonged and aggravated by the infusion of dopamine. PMID- 2098599 TI - [Anesthesia for pectus excavatum]. AB - The incidence of arrhythmia, postoperative complication and pulmonary oxygenation (PaO2) were studied in 48 patients with pectus excavatum scheduled for the Ravitch operation under halothane-nitrous oxide-oxygen (GOF) and enflurane nitrous oxide-oxygen (GOE) anesthesia. Preoperative abnormalities of ECG were observed in 36 of 18 cases. Main abnormalities were incomplete right bundle branch block, left atrium enlargement, and sinus arrhythmia. Ventricular arrhythmia was observed in 4 of 12 cases during GOF anesthesia, whereas no arrhythmia was observed during GOE anesthesia. In postoperative chest X-ray, pulmonary atelectasis (60%), pleural effusion (48%), and pneumothorax (8%) were observed. The results suggest that GOE is more advantageous for pectus excavatum operation than GOF. Postoperative pulmonary surveillance is important for pectus excavatum operation. PMID- 2098600 TI - [Another mishap with Mera-F Circuit: a break in the socket]. AB - Troubles with the inspiratory limb have been noted with the reuse of the Mera-F Circuit. However, to our knowledge there have been no reports of the mishap in socket that is made of polycarbonate material. The case we present is a mishap due to the fracture of socket with the reuse of the circuit under general anesthesia. After the operation, the breaks were discovered in four of six other circuits reused. Although the cause of the break is unknown, it is speculated that enflurane or ethylene oxide gas may impair the polycarbonate material. Clinically, we recommend that Mera-F Circuit should be inspected carefully before its reuse. PMID- 2098601 TI - [Differentiation of brain stem anesthesia from high spinal anesthesia using auditory brain stem response]. AB - A 67-year old woman having intractable chronic postherpetic neuralgia at the neck to forearm for two years was treated with subarachnoid block. Initially, bolus of 1% lidocaine 8 ml, with methylprednisolone acetate 20 mg was injected intrathecally at 6th cervical intervertebral space. The auditory brain stem response (ABR) during high spinal block with intact consciousness was not depressed in its wave height. ABR recorded showed prolongation of latency of 3 and 5 waves and prolongation of 1-3 phase to phase interval without prolongation of 3-5 phase to phase interval. Intrathecal nerve block was then performed with 1% lidocaine 15 ml and methylprednisolone acetate 20 mg, because she complained awareness and shocking sensation with controlled respiration during the first block. She assured that she felt nothing during the second block. The ABR recorded during the second block showed near complete suppression in its height of all waves and prolongation of all wave latencies. During recovery period, 1-3 and 3-5 phase to phase interval prolongation was recorded. One can differentiate brain stem anesthesia from other state that induces unconsciousness after block which is capable of inducing accidental brain stem anesthesia. These two blocks improved activity of daily living of the patient and severity of her pain decreased to 1/5 to 1/10. PMID- 2098602 TI - [Severe lightning pain during spinal anesthesia]. AB - A 74-yr-old man was scheduled for the biopsy of prostatic tumor under spinal anesthesia. Preoperative serologic test for syphilis was highly positive. Spinal anesthesia was performed in the sitting position, and 2 ml of hyperbaric Neo percamine S (a mixture of 0.24% dibucaine and 0.12% T-caine) was administered uneventfully with the onset of warm sensation on the perineal region. Ten minutes later, however, he began to complain of severe lightning sensation on the feet. After giving pentazocine intravenously, the short cystoscopic procedure was completed. As a cause of severe pain, an erroneous anesthetic solution or direct neuronal injury had been excluded because of rapid and complete recovery after anesthesia. Two weeks later, he was scheduled for TUR-P. He again complained of severe lightning pain after the successful spinal anesthesia with the same anesthetic solution. Because the pain was not relieved by analgesics, he was then anesthetized with enflurane and N2O in oxygen, and there were no neurological complications after anesthesia. Several cases of severe pain during spinal anesthesia have been reported in patients with tabes dorsalis. Although the patient lacks clear symptoms of neurosyphilis, positive serologic examination for syphilis without any other possible causes suggests altered sensitivity of the spinal cord to anesthetic solutions. PMID- 2098603 TI - [The present status and problems of repatriation in France]. AB - In France, repatriation, the inter-continental or interhospital critical care transport, is done on a large scale mainly by private companies with sophisticated medical knowledge, techniques and equipment. They offer a great assistance to SAMU when a disaster occurs. It is notable that almost all doctors who work for these companies are anesthesiologists and trained in SAMU. Repatriation is a large field involving critical care transport which includes intensive care medicine and disaster medicine as well as emergency medicine. One of the most important things about repatriation is that the judgement should be done and means of transport of the patient should be decided based purely on medical grounds. PMID- 2098604 TI - [Pioneers of spinal anesthesia in Japan: the achievements of Nan-su Pak]. PMID- 2098605 TI - [Current aspects of the therapy of bronchial asthma in childhood]. AB - The management goals common to all age groups are to reduce symptoms, to permit a normal physically active lifestyle, and to prevent irreversible airway obstruction. Main measures are environmental manipulation (avoidance of allergen contact, cigarette smoke and pets; psychotherapeutic management), assessment of severity, training for self management, hyposensitization (pollen, HDM, insect venoms) and pharmacotherapy. Medication should be adapted to age and severity of the disease, and the different drugs should be used stepwise. The first step includes the application of bronchodilators in which beta-2-stimulants are to be preferred. If we use spacers or jet nebulizers infants can also be treated successfully. The value of xanthines is discussed controversially. The next steps tend to reduce the inflammatory reaction. In this direction sodium cromoglycate and ketotifen are useful especially in childhood, and inhaled steroids have increasing importance. The use of oral corticosteroids should be the last step. PMID- 2098606 TI - [The use of vitamin E in childhood]. AB - The essential effects of Tocopherol are based on its antioxidative capacity. Tocopherol, however, is just one in a group of antioxidants, which are important for the organism. Established indication for therapeutical application of vitamin E in infancy is only vitamin-E-malabsorption in connection with chronic cholestasis, pancreatic insufficiency (cystic fibrosis) and short bowel syndrome. In emergency therapy vitamin E is suggested with high dosage in case of shock lung and haemolytic-uraemic syndrome. Positive effects of daily vitamin E application in connection with prophylaxis of retinopathy prematurity, bronchopulmonary dysplasia and intraventricular encephalorrhagia of premature infants of severe underweight are not established. Very questionable therapeutic or prophylactic efficiency is opposed to the risk of higher incidence of severe complications in caring for premature infants of severe underweight, such as enterocolitis necroticans and neonatal septicaemia. PMID- 2098607 TI - [Malignant tumors of lung and bronchi in children and youth. 3. Diagnosis, differential diagnosis and therapeutic approach]. PMID- 2098608 TI - [Quantitative two-dimensional echocardiography. Study results in patients with cystic fibrosis]. AB - 15 patients with cystic fibrosis aged 8-19 years were graduated into 3 stages of the cor pulmonale dependent on results of an examination with the microcatheter: stage 0:6, stage I: 4 and stage II: 5 patients. These patients were studied in the period from April 1987 to January 1988 echocardiographically. With this size and contractility of the right ventricle were especially considered. The end diastolic and end-systolic area of the right ventricle could be measured in the apical 4-chamber-view in 14 of the altogether 15 patients and out of this the fractional area-shortening could be calculated. The end-diastolic area of the right ventricle in the patients with stage 0 was on an average 11.4 cm2/m2 body surface bs (8.7-13.5), in stage I 11.2 cm2/m2 bs (9.2-13.5), and in stage II 9.7 cm2/m2 bs (9.0-10.8). The end-systolic area of the right ventricle in stage 0: 7.2 cm2/m2 bs (6.8-8.4), stage I: 7.1 cm2/m2 bs (6.0-8.5), and stage II: 8.02 cm2/m2 bs (6.4-10.1). The results we found don't differ significantly in the 3 groups. Contrary to this fractional area-shortening of the right ventricle shows a falling tendency: stage 0.35.2% (22-49), stage I 32% (7-56), stage II 17.2% (4 38) with an increasing part of patients with a value under 28% (stage 0:1 patients, stage I 2 patients, stage II 3 patients). Contractility and pump efficiency of the left ventricle were calculated in the apical 4-chamber-view according of the area-length-method. The findings don't show an increasing size of the right ventricle in the sense of a cor pulmonale but a decreasing contractility and pump-efficiency of the right ventricle as expressions of a cardial manifestation of the basic illness in the sense fo a symptomatic cardiomyopathy. A disturbance of the contractility of the left ventricle could be seen in 7 of the 15 patients (47%). PMID- 2098609 TI - [Occlusion of the gastric outlet caused by a trichobezoar]. AB - Bezoars are concretions formed in the gastrointestinal tract. The trichobezoars are hairballs in the stomach or intestines composed of hair. They are usually found in young girls as in our case which we operated in April 1989 on Surgical Ward in Kartal State Hospital in Istanbul. The postgastrectomy state predisposes to bezoar formation. Persimmon peels or pits, orange or grapefruit pulp are the usual offenders. Bezoars are associated with vague upper gastrointestinal discomfort, nausea, and vomiting. The patients may complain of abdominal pain. Ulceration, bleeding, obstruction, and perforation are the most common complications. Treatment consist of mechanical fragmentation via the endoscope or operative extraction. Dissolution of the undigested bolus by ingestion of proteolytic enzymes such as papain may be tried. As prophylaxis the postgastrectomy patient must be warned of ingesting citrus fruits. PMID- 2098610 TI - [Recommendations for the diagnosis and therapy of meningitis, Waterhouse Friderichsen syndrome and encephalitis in childhood]. AB - Representatives of the working group of "Neuropaediatrics" and "Infectology" like to present recommendations on diagnostics and treatment of infectious diseases on the CNS. Individual opinions can not be considered in recommendations always. Therefore we have to understand these recommendations in this way that individual decisions will not be restricted in special situations. PMID- 2098611 TI - [Pediatric vaccination advice: prophylactic vaccination (pertussis/measles/influenza) in infants and young children with chronic bronchitis due to bronchopulmonary dysplasia following neonatal intubation and respiratory therapy]. PMID- 2098612 TI - [Pediatric vaccination advice: reactive arthritis and immuno-vasculitis with cardiovascular shock following triple prophylactic vaccination (diphtheria pertussis-tetanus)]. PMID- 2098613 TI - [Opinion on childhood tuberculosis. A review]. PMID- 2098614 TI - [Significance of EEG findings in pavor nocturnus]. AB - Sleep disorders have an incidence of approximately 65 percent in early childhood. Etiologic there are constitutional and neurotic factors in night terror. Neurophysiologically it occurs at fast arousal out of non-REM-sleep. There are no relations to epilepsy, also not at existence of spike potentials in the EEG. At a cross-sectional examination of 20 children with pavor nocturnus 14 exhibited sharp waves and one SW. The EEG can hint at constitutional factors, retardation of cerebral maturation, but psychological examination is in severe cases more useful for effective therapy. PMID- 2098615 TI - [Individually-adjusted dosages of aminophylline in children with bronchial asthma]. AB - Theophylline concentrations in serum between 10 to 20 micrograms/ml cannot be obtained with usual dosage of theophylline in children with individual very short elimination half time of theophylline. Multiple corrections of dosage and repeated controls of theophylline concentrations in serum are necessary for empirical adjustment of individual optimal dosage. Pharmacokinetic investigations were made to shorten this management. 12 patients with bronchial asthma, 6 to 18 years of age, received 1.5 to 3 tablets of Aminophyllin under conditions of steady state. Blood samples were taken up to 6 hours after oral application. As a result of statistical analysis we found that the biological half time of theophylline could be determined from 2 to 3 blood samples. Estimation of optimal individual dosage is possible by simple mathematical pharmacokinetic formulas. PMID- 2098616 TI - [Minimal cerebral hemorrhage in premature infants]. AB - Under the term minimal cerebral haemorrhage we understand subependymal haemorrhages which occur as a consequence of ruptures in the capillaries in the stratum germinativum. They occur exclusively in newborn babies after the 36th week of pregnancy. In premature babies born up to or after 32 weeks we found these haemorrhages to a degree of 45% in cases where there was also more haemorrhage. We did not discover any neurological abnormalities in the development after birth as a result of isolated subependymal haemorrhage. This makes the question of how and in how much detail the parents should be informed about the findings more acute. On questioning the relatives it was found that they had undergone some uncertainty and psychological strain after being informed about the findings. PMID- 2098617 TI - [Infrared diaphanoscopy (IRD)--a choice diagnostic procedure? Preliminary results of the clinical testing]. AB - X-ray examinations of maxillary sinus represent an exposure to radiation not to be ignored especially in infancy and childhood. The diagnostic method of infrared diaphanoscopy (IRD) is described. As a method of choice it is compared with other possibilities of diagnosing inflammatory diseases of the maxillary sinus. No exposure to radiation, easy application as well as low costs and small demands on the equipment are essential advantages of this method. First results have already shown its clinical relevance. PMID- 2098618 TI - [Heinrich Finkelstein (1865-1942)--pediatrician and pioneer in social pediatrics. A biographical sketch]. PMID- 2098619 TI - [Infant mortality and its control. 1905]. PMID- 2098620 TI - [Pediatric vaccination advice: prophylactic vaccination in an infant with chondrodystrophy (Conradi-Hunermann syndrome), Increased serum transaminases and chronic obstructive bronchitis]. PMID- 2098621 TI - [Pediatric vaccination advice: Prophylactic vaccination against pertussis, measles and influenza in children with a prolonged RS-virus infection (recurrent or chronic obstructive bronchitis/prolonged bronchiolitis)]. PMID- 2098622 TI - [Child abuse in "really existing socialism"]. PMID- 2098623 TI - [Diagnostic aspects in child abuse]. AB - In connection with diagnostic and treatment of children the paediatrician may also be confronted with suspected by or certainly abused children. In those cases an evidence on necessary legal consequences will be useful. Anamnesis, examination and radiography have traditionally been used to assess the injuries of abused children. Sceletal scintigraphy should be the screening procedure of choice for children with bone injuries suspected or certainly having been abused. Cranial computer tomography is a recent method to detect intracranial lesions and cerebral late effects due to violence in abused children. PMID- 2098624 TI - [The problem of child abuse and neglect. 1: Analysis of hospital treated pediatric and pediatric surgical patients]. AB - Definitions, legal aspects, epidemiology and the author's experience in 58 relevant cases between 1966 and 1986 are described and recommendations for diagnosis, notification and prevention are given. The author underlines the importance of the early detection of the maltreatment and neglect of children and the conclusions to be drawn. PMID- 2098625 TI - [Consequences of the composition of human milk for the nutrition of low-birth weight neonates. III. Sodium and potassium]. AB - The concentrations of sodium and potassium were studied in the 24 hour pooled human milk of 37 mothers delivered preterm (PTM) and of 19 mothers delivered at term (TM) from the second to the eighth postnatal day and in addition in the PTM during the third week of lactation. During the 4th week of life the sodium balance was estimated in 31 very low birth weight infants fed a human milk formula enriched with NaCl (n = 11) or NaH2PO4 (n = 11) and in 9 infants fed the same formula without supplementary sodium. The concentrations of sodium decrease significantly during the first week of lactation. The values are significantly higher in PTM than in TM during the first 3 days but decrease in both milks to values between 1 and 2 mmol/100 ml. The concentrations of potassium increase up to the 4th day of lactation and fall to approximately 1.5 mmol/100 ml at the end of the first week of lactation. There are no differences between PTM and TM. In all three balance groups the sodium balance are positive. But only in the infants fed a sodium-supplemented human milk formula the weight gain was adequate according to the protein and caloric intakes. No signs of a pathological sodium retention could be observed during the balance period. The data suggest that a sodium intake of more than 2.5 mmol/kg/day is necessary for optimal growth. Thus, the phosphorus supplementation should be done generally as 1 mmol NaH2PO4/100 ml human milk in very low birth weight infants. PMID- 2098626 TI - [The fundamental pulmonary mechanics processes in pressure-limited artificial ventilation of neonates]. AB - During the past years the incidence of artificial ventilation in newborn and premature babies increased continuously. The optimization of the respirator therapy requires the knowledge of the fundamental lung mechanic processes during the artificial ventilation. Using the simple model RC V(t) + V(t) = CP(t) the relationships between the flow, volume and pressure signals were demonstrated. This model was also used to explain the development of the inadvertent PEEP as well as to determine lung mechanic parameters from the measured signals. In the future the monitoring of tidal volume will be an integrated part of the respirator. Therefore, the influence of the lung mechanics and the parameter settings of the respirator on the ventilation has been investigated in detail. PMID- 2098627 TI - [Albrecht Peiper (1889-1969) in Greifswald]. PMID- 2098628 TI - [Sudden infant death and home monitoring]. PMID- 2098629 TI - [Open letter from initiative group of pediatricians, psychologists, child caregivers and parents about early childhood care and day care centers]. PMID- 2098630 TI - Antibodies to Borrelia burgdorferi in dogs in Hokkaido. AB - During 1985 to 1990, serum samples were obtained from 229 healthy dogs. The dogs lived in Hokkaido, known to be infested with ticks. An enzyme-linked immunosorbent assay (ELISA) was used to detect IgG and IgM antibodies against Borrelia burgdorferi HO14 and HP3, which were isolated from Ixodes ovatus and I. persulcatus in the area. IgG antibody to B. burgdorferi HO14 was detected in 8.8% (1985), 16.4% (1987) and 18.5% (1990). IgM antibody to the bacteria was detected in 1.8% (1987) and 2.5% (1990). Antibodies to the strain HP3 of B. burgdorferi were also detected in the serum samples of dogs, but the percentage of seropositive sample to the strain HP3 was lower than that to the strain HO14. Statistical differences were not noticed between pet and street dogs. No antibody to B. burgdorferi was observed in 13 beagle dogs as experimental animal. PMID- 2098631 TI - Ia restriction specificity of KLH-specific T cells from allogeneic bone marrow chimeras is influenced by histocompatibility at the H-2 and minor histocompatibility loci. AB - Ia restriction specificity involved in T cell proliferative responses to keyhole limpet hemocyanin (KLH) has been analyzed using a variety of allogeneic bone marrow chimeras. The chimeric mice were prepared by reconstituting irradiated AKR, SJL, B10.BR and B10.A(4R) mice with bone marrow cells from B10 mice. When such chimeric mice had first been primed with KLH in complete Freund's adjuvant (CFA), T cells from H-2 incompatible fully allogeneic chimeras showed significantly higher responses to KLH in the presence of antigen-presenting cells (APC) of donor strain (B10) than APC of recipient strain. However, in H-2 subregion compatible chimeras, [B10----B10.A(4R)], which were matched at the H-2D locus and at minor histocompatible loci, the T cells could mount vigorous responses to KLH with antigen-presenting cells (APC) of either donor or recipient type. The same results were obtained as well with chimeras that had been thymectomized after full reconstitution of lymphoid tissues by donor-derived cells. A considerable proportion of KLH-specific T cell hybridomas established from [B10----B10.A(4R)] chimeras exhibited both I-Ab and I-Ak restriction specificities. The present findings indicate that the bias to donor Ia type of antigen specific T cells is determined by donor-derived APC present in the extrathymic environment but that cross-reactivity to the recipient Ia is influenced to some degree by histocompatibility between donor and recipient mice, even though the histocompatible H-2D locus and minor histocompatibility loci seem not to be directly involved in the I-A restricted responses studied herein. PMID- 2098633 TI - The occurrence of alpha (1----2) linked N-acetylperosamine--homopolymer in lipopolysaccharides of non-O1 Vibrio cholerae possessing an antigenic factor in common with O1 V. cholerae. AB - Chemical analysis was carried out on lipopolysaccharides from Vibrio cholerae bio serogroup Hakata 487-85. The O-specific chain of the phenol-soluble lipopolysaccharides was demonstrated by 13C-NMR spectroscopy and methylation analysis to contain a linear homopolymer of alpha(1----2) linked N acetylperosamine (4-acetamido-4,6-dideoxy-D-mannopyranose), which was closely similar to but not identical to a linear alpha(1----2) linked N-3-deoxy-L glycerotetronyl (S-2,4-dihydroxybutyryl) perosamine-homopolymer constituting that of O1 Vibrio cholerae lipopolysaccharides. PMID- 2098632 TI - The nucleotide and deduced amino acid sequences of EcoRI fragment containing the 5'-terminal region of Clostridium botulinum type E toxin gene cloned from Mashike, Iwanai and Otaru strains. AB - Chromosomal DNAs were extracted from toxigenic three Clostridium botulinum type E strains isolated from food-borne botulism. After digestion by EcoRI, the fragments were cloned into Escherichia coli by using bacteriophage lambda gt11 and screened with monoclonal antibody recognizing the light chain component of botulinum type E toxin. The fragments (about 1 kbp size) cloned from each strain were recloned into a plasmid vector pUC118. The E. coli cells transformed with the recombinant plasmids produced 33 kDa protein with or without IPTG (isopropyl beta-D-thiogalactopyranoside) which reacted with the monoclonal antibody. The nucleotide sequences of the cloned EcoRI fragments from the three type E strains were identical and contain the 5'-terminal region of the type E toxin gene. It was also found that there exist several highly homologous nucleotide sequences among the botulinum types A, C and E, and tetanus toxin genes in both translated and untranslated regions. PMID- 2098635 TI - Growth physiology of mycobacteria in modified Dubos liquid medium. AB - Although mycobacteria grow in Dubos liquid medium showing an arithmetic linear growth, the initial few days of growth were found to correspond to an 'induction' period. In this period, rapid increase of the amount of growth occurred, whereas increase of the number of colony-forming units remained at a low level. This finding shows that the rapid increase of the amount of growth is accompanied by rapid death of multiplied bacteria. In a successive period, which was considered to correspond to the logarithmic growth phase, a 1:1 correspondence existed between the amount of growth and the number of colony-forming units. The induction period is not considered to be a lag phase, in which the bacteria grow slowly, but a period of unbalanced relationship between the growth and the viability. Even when we inoculated different sizes of bacteria, the amounts of growth became similar in both inoculations after several days of incubation. However, the number of colony-forming units remained always smaller in the use of small inocula than in the use of large inocula. In the use of small inocula, much more rapid increase of the amount of growth occurred. However, this rapid increase gave rise to rapid death of bacteria. PMID- 2098634 TI - Interaction between two distinct plaque-cloned human immunodeficiency viruses (HIVs): the possible existence of heterozygous virus. AB - To know the biological significance of the HIV variation, we investigated the interaction between two different HIV clones. Two distinct clones were mixed and propagated by infecting MT-4 cells. After passaging the mixture viruses 8 times, and cloning by the plaque method, we obtained not only viruses of homogeneous type like each parental clone but also heterogeneous-type viruses which showed a mixture of two parental viruses with regard to phenotype and genotype. To further segregate a single virus from the mixture, we recloned the heterogeneous viruses using the plaque method. We found that about 40% of recloned viruses from heterogeneous-type viruses were still heterogeneous. PMID- 2098636 TI - [Fatty substances in the adrenal cortex after exposure to chemical contaminants]. AB - The content of fatty substances was examined: neutral fats, triglycerides and phospholipids, in the adrenal gland cortex after exposing white rats to the influence of detergents in the duration of one month. Neutral fats conduct themselves in the following manner: their quantity is decreased in the cells of zona glomerulosa and is increased in the zona fasciculata and zona reticularis. As far as the presence of triglycerides in the adrenal cortex is concerned, it is typical that they are increased quantity-wise in all three zones of the adrenal gland cortex. Phospholipids in their presence, give the following appearance: this group of fatty substances is of increased content in the cells of zona glomerulosa; a slight increase of these substances is typical for zona fasciculata while their increase is evident in the cells of zona reticularis. All of the described features, regardless of the group of fatty substances, indicate the stimulated activity of the adrenal gland cortex after the application of histochemical methods. PMID- 2098637 TI - [Histological picture of the subcommissural organ in chronic alcoholism in rats]. AB - In the course of a three-month administration of 15% ethyl alcohol solution as the only liquor offered to the experimental rats, SCO characteristics were analysed by methods of light microscopy, and SCO height measurements and by measuring the volume of the ependymocyte nuclei. There was abundant vacuolization of individual ependymocytes, as well as in groups of them, and increased apical and subapical neurosecretory accumulations. The volume of the nucleus was significantly augmented, whereas the SCO height remained within the limits of the control values. The changes obtained corroborate the idea of an active engagement of the SCO in the course of chronic alcohol consumption by experimental rats. PMID- 2098638 TI - [Radiographic measurement of the antebrachiocarpal joint in dogs]. AB - Radiographic processing of the antebrachiocarpal joint was conducted in 30 sexually mature dogs of different race, sex and body weight. Anteroposterior and profile radiograms of joints were made in standardized conditions. The aim of this paper was to determine the qualitative radiographic characteristics of the antebrachiocarpal joint in dogs, and the possibilities of applying various radiographic parameters in quantitative radiographic investigations of this region. The observed differences in the morphology of this joint in dogs in relation to the one in humans, are the result of evolutionary racial adaptation. By knowing these differences it is possible to adjust the radiographic measurement parameters which are in clinical practise use, and in that way enable the full use of dogs as experimental models in radiographic and surgical research projects. PMID- 2098639 TI - [Specific psychomotor organization in a child with phocomelia]. AB - The authors follow the specific development of a child with phocomelia. Psychomotoric organization was analyzed in the period prior to starting school and before the child became literate. The existence of specific forms and outlines of catching movements was established. The lower extremities developed a compensatory--fine motorics mechanism of toe abduction. A drawing of a human figure expressed the specific experiencing of the body scheme as the "losing" of the upper extremities. Left-handedness was discovered. Typical difficulties exist in the forming of the number conception. Preparations are being done for the mastering of the use of the intelectual prosthesis-computer. PMID- 2098640 TI - [The McCune-Albright syndrome with hyperthyroidism, acromegaly and hypophosphatemic-hyperphosphaturic rickets]. AB - A girl was described with an unusual combination of McCune-Albright's syndrome (polyostotic fibrotic dysplasia, hyperpigmentations on the skin and precocious puberty) with hyperthyroidism, hypophosphatemic-hyperphosphaturic rickets and acromegaly. Although the pathogenetic mechanism involved in the development of this endocrinopathy in this syndrome is not quite clear, the achieved results, as well as data of other researchers, suggest that the endocrinological disorders in this syndrome are the result of either an increased sensitivity of periphery endocrine organs or/and of an autonomous hyperfunction (similar to multiple endocrine adenomatosis). PMID- 2098641 TI - [Psychological manifestations in hypothyroidism]. AB - Although psychic changes are an integral part of the clinical manifestations of hypothyrosis, in traditional literature it is always especially pointed out that this category of patients usually acquires the conditions for developing rough disorders, psychoses. Nevertheless, the results of this study indicate that the most frequent psychic changes are mild and atypical depressions, and that their frequency isn't greater in relation to previously studied patients with hyperthyrosis. PMID- 2098642 TI - [Radionuclide functional tests in transplanted kidneys]. AB - Results of 140 combined first-pass and dynamic functional renal studies were clinically evaluated in 50 patients with a transplanted kidney. The renal handling of three different nephroaffine radionuclides, namely the glomerular agent (99m Tc-DTPA), the predominantly tubular agent (99m TcMAG3) and combined glomerulo-tubular agent (99m Tc-PAHIDA) was also analysed in various dysfunctions of renal transplants. It has been concluded, that the clinically most useful information at all levels of the overall renal function has been given by 99m TcMAG3. However, the behaviour of glomerular and tubular agents in postischaemic acute tubular lesion was found to be discordant which in turn could be valuable differential-diagnostic information, and out of this reason their successive application is essential. The combined firstpass and dynamic functional renal studies have been judged as a helpful diagnostic tool in the follow-up of patients who have undergone kidney transplantation, provided that its results are interpreted in the light of clinical and other relevant findings. PMID- 2098643 TI - [Anesthesia in peritoneovenous shunt placement]. AB - Since 1984 the peritoneovenous shunt has been installed in 33 patients because of resistant ascites. The aim of this study was to find the optimal type of anesthesia in our conditions on our own clinical-patient material. All patients were classified by the ASA, Goldman, Child and Child-Puigh score. The patient, surgeon and anesthesiologist were polled about the quality of anesthesia, and all observed complications were followed, like after different premedications as well as in the course and after different types of neuroleptic anesthesia. General neuroleptic anesthesia was applied in 23 patients (69.7%), one was operated on in ketamine anesthesia (3.0%) and 9 (27.3%) in local anesthesia with 2% Xylocaine. After premedication with Thalamonal in all patients there came to a fall in arterial pressure for more than 20% of initial values and the feeling of uneasiness and fear was present. All patients with local anesthesia absolutely needed additional application of sedation or analgesia, especially during the formation of the subcutaneous tunnel, and neither patient nor surgeon were satisfied with the achieved comfort. During the course of neuroleptic anesthesia with Thalamonal hypotension developed, in 17/20 patients an in 2/20 the presence of prolonged apnea demanded additional artificial ventilation. In the patient operated on in ketamine anesthesia, an acute psychotic reaction developed, followed by visual and acustic hallucinations without signs of metabolic encephalopathy. On the basis of our own experience, we conclude that general neuroleptic anesthesia with the use of Flormidal as an anesthetic and Fentanil as an analgetic, is the method of choice, and that local anesthesia can be recommended only on one operative site (except the subcutaneous tunnel). PMID- 2098644 TI - [Radioimmunologic determination of growth factors. II. Comparative development of methods for the determination of hematopoietic growth factors]. AB - On the basis of our long-term experience, presented are the current clinically useful methods for determining erythropoietin, the granulocytopoiesis growth factor and thrombocytopoietin with the results in their use. Facts are shown, concerning the long-used method of determining erythropoietin through the use of the biological test on polycythemic mice. In our conditions, mice treated with physiological solution (negative controls) have a Fe-59 incorporation below 0.5% of the given dose, while 0.2 units of the international erythropoietin standard (positive control) increases that incorporation to 3.0%. Also presented, are results of determining erythropoietin by means of the newest immunometric method which has shown exceptional features: the whole procedure, including necessary rinsings, lasts about six hours, and it is possible, in the course of one work day, to all at once precisely determine the erythropoietin concentration in 80 samples of human serum. This fact, as well as the outstanding sensitivity of the method which is about 2 mJ/ml (that is 50 times the sensitivity of the biological test) has as a result, the wide introduction of erythropoietin determination in the clinical use of today and the definition of its clinical importance. The measurement range of the method is from 2-200 J/L which can be extended further by specimen dilution. It is especially important that duplicate measurements at one point of the curve almost coincide, which indicates great method precision. The lowest measured concentration in our series amounted to 0 J/L and the greatest to greater than 250 J/L. Elevated values were found in 17 of the 114 serums.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098645 TI - [Obytin in the treatment of superficial skin mycoses]. AB - Obytin (1% Cyclopyroxolamine) in the form of cream, a preparation of the firm Jugoremedija/Hoechst, was applied in the treatment of 33 patients with dermatophytic skin infections. The diseases were most frequently located in the intertriginous areas 19 (57%), somewhat less frequently on nude places of the skin 9 (27%), and on the hands and feet 5 (16%). The cream was applied twice daily for 28 days. Acute clinical symptoms of the disease disappeared rapidly under the influence of the preparation and disappeared completely after three weeks of treatment in 32 patients (97%); and four weeks after start of therapy mycology tests were negative in the same number of cases. Only 3% of patients had no evident changes during therapy. Obytin is one of the new topical antifungal agents with a wide spectrum of action and it can be used in all types of superficial dermatomycoses as well as in some bacterial infections. It is characterized by rapid onset of action. Side effects of local or systemic nature (irritative, alergic or toxic) had not been registered. PMID- 2098646 TI - [Epidemiologic and clinical approaches in the prevention of carcinoma of the uterine cervix]. AB - The current state of the epidemiology and the clinical results of UCC in our surroundings is not satisfactory and is irregular according to different parts of Yugoslavia. In the purpose of attaining a better view of the state in our surroundings, 1957 sexually mature females were polled in the territory of Novi Sad during 1987-1988 (1000 were unemployed and 957 employed) thus we will use parts of this poll in the areas which are of interest for the problems studied. According to our survey, most of the women were unadequately and unsufficiently informed about the causes of uterine cervix diseases, therefore little attention is given to the early start of sexual intercourse (1.7-2.7%), the changing of several sexual partners in a lifetime (5.5-9.8%), hygiene of male sexual organs (1.6-18.7%), and the role of abortions was overestimated (11.5-14.7%) with a considerable number of uncertain responses (22.4-2.6%). Almost 50% of the polled women do not know any possibilities for the individual prevention of UCC risk factors. Most of the women in both of the categories polled (66.0-46.6%) express the opinion that the necessary knowledge should be acquired in these areas through regular education which should be conducted at a suitable age, and there are less of those which think that this knowledge should be acquired through other sources of information (women's magazines or means for public informing and so on).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098647 TI - [Correlation between certain parameters in pregnancy and body weight and the vitality of the neonate]. AB - An analysis of 2280 puerperas who delivered newborns with the birth weight of 2500 g up to over 4000 g in the first half of 1989 at the Clinic for Obstetrics and Gynecology in Sarajevo had been conducted. Age, parity, body weight increase during pregnancy, and their socio-economic status was investigated. All newborns were divided into several groups according to birth weight: 2500-3000 g, 3000 3500 g, 3500-4000 g and over 4000 g. Puerperas with hypertension before pregnancy, EPH gestosis, anaemia and pyelonephritis were excluded. It has been found that newborns with birth weight between 3000-3500 g, the most desirable weight, were delivered by mothers who had a body weight increase of about 12.6 kg during pregnancy. Their average age was 25 years among primiparas, and 27 among multiparas; they were high-school graduates. American authors consider a weight increase of 8 kg during pregnancy as the most ideal for a good outcome. Vitality of newborns measured by the Apgar score was satisfying, with minor deviations in the group with birth weight over 4000 g. PMID- 2098648 TI - [Serologic diagnosis of toxoplasmosis]. PMID- 2098649 TI - [Tubercular Addison's disease with high titers of microsomal thyroid antibodies and reduced thyroid function reserve]. AB - This case reports deals with a male patient, white, aged 51, bricklayer, tobacco smoker. At 43 years old a tubercular epididimite was surgically treated with orchiectomy. Recently, the reports marked weakness, weight loss, headache, vertigo, hypotension. On admittance to the hospital, hyperpigmentation was also present. Previous therapy (cortisone acetate 40 mg/die), was suspended, clinical investigations showed impaired adrenal and thyroidal functions; antimicrosomal antibodies were also present. Therefore therapy with cortisone acetate (25 mg x 2/die, 9-alpha-fluorohydrocortisone 0.1 mg/die and L-thyroxine 100 mcg/die) was instituted with marked improvement of the patient's conditions. This case reports highlights the importance of proceeding with complete investigations on the system, even when dealing with a tubercular Addison's disease. PMID- 2098650 TI - [Beta-pancreatic function in adult patients with GH deficiency]. AB - We investigated the beta-pancreatic function in response to a standard oral glucose tolerance test (OGTT) and a tolbutamide test in a group of GH-deficient adult subjects and in a group of control subjects. Fasting plasma glucose levels were normal in all subjects; the insulin levels, basal (0.19 +/- 0.02 vs 0.99 +/- 0.08) and, as n-AUC, after OGTT (195.2 +/- 23 vs 520.5 +/- 69) and tolbutamide test (33.6 +/- 4.4 vs 177.7 +/- 12.1) (means +/- ES), were significantly lower (p less than 0.001) in the GH-deficient subjects compared to controls. These data indicate a reduced beta-cell activity, secondary to absence of trophic effect of GH on pancreatic beta-cells, in GH-deficient adults. PMID- 2098651 TI - [Advances in insulin treatment. Evaluation of isophane or lente insulin, mixed with rapid insulin and injected twice-a-day]. AB - When mixed with lente insulin, regular insulin undergoes a slowing down in its absorption rate, which does not occur when it is mixed with isophane insulin. However, there is not sufficient evidence to state that this phenomenon affects the quality of the metabolic control in subjects treated with two daily mixtures of regular + intermediate insulins. This parallel study compared in a 12-month follow-up the results achieved in 154 insulin-dependent diabetics (IDD) treated with extemporary mixtures injected before breakfast and dinner, with the purpose of verifying whether the mixture regular + isophane offers specific advantages compared to regular + lente. The 79 IDD who have used isophane insulin and the 75 IDD treated with lente insulin had similar personal and clinical findings. During the 12-month study, the improvement of glucose profile, the number and the severity of hypoglycaemic episodes as well as the insulin requirement resulted almost overlapping with the two treatments. In conclusion, the results of this study confirm that the mixtures of regular + isophane insulins (Actrapid HM + Protaphane HM) and regular + lente insulins (Actrapid HM + Monotard HM) give the same guaranties of safety and efficacy, that the former shows a more rapid absorption rate and, finally, indicate that the ratio 30:70 between regular and intermediate insulins is that more frequently used. PMID- 2098652 TI - [Assessment of bone resorption/neoformation indexes in obese women before and after weight loss]. AB - Serum osteocalcin and alkaline phosphatase levels, as indexes of bone formation, and urinary calcium and hydroxyproline excretions relative to creatinine, as indexes of bone resorption, were measured in 10 obese women before and after two months of hypocaloric diet. In basal condition, serum osteocalcin, but not alkaline phosphatase levels, were higher in obese than in controls (7 +/- 0.4 vs 5.3 +/- 0.2 ng/ml). Urinary calcium/creatinine and hydroxyproline/creatinine ratios were also significantly higher than those in normals (0.37 +/- 0.05 vs 0.2 +/- 0.01 and 0.035 +/- 0.004 vs 0.02 +/- 0.002, respectively). After weight loss, serum osteocalcin significantly increased (9.5 +/- 0.5 ng/ml), while urinary calcium/creatinine and hydroxyproline/creatinine ratios fell to the normal values (0.23 +/- 0.03 and 0.026 +/- 0.001). In conclusion, it appears that obesity, at least in young women, is associated with a high bone turnover, which seems to be reversible with weight loss. PMID- 2098653 TI - [The role of opioid antagonists in the treatment of obesity. Results of a clinical trial with naltrexone]. AB - On the basis of literature data relative to the alteration of beta-endorphin tone in obese subjects, we conducted a clinical trial employing Naltrexone (a receptorial antagonist of endogen opioids) in order to evaluate its efficacy in increasing the compliance of these subjects on dietary treatment. The drug dosage was 50 mg/daily (100 mg/die). The clinical study was carried out following the double-blind crossover method for a period of 4 months in a group of 17 obese subjects who also underwent to psychodiagnostic interviews. Significant weight reduction was observed in the 9 patients who carried out the treatment by assuming Naltrexone (kg 4.00 +/- 3.97) rather than with placebo (kg 0.96 +/- 4.95). The drug was subjectively well tolerated and it did not alter the endocrine, metabolic, psychometric, and cardiovascular monitored parameters. The insulin secretion during OGTT did not show significant alterations. Our data emphasize the Naltrexone efficacy in improving the compliance of the obese subjects during dietary treatment. PMID- 2098654 TI - [Possible correlations between protein-loosing nephropathy and obesity]. AB - Nephrotic syndrome has been reported in obesity; its precise incidence in obese patients without diabetes mellitus and/or arterial hypertension is however unknown. Thirty-two obese subjects without complications were therefore assessed before and after weight loss, together with 18 healthy control subjects. Overnight albumin excretion rate (AER) was assessed using a RIA method (H. Albumin-Kit, Sclavo). Glomerular filtration rate (GFR) was also evaluated in 10 obese subjects using Cr51 before and after weight loss. AER was found to be higher, although the difference was not statistically significant, in obese subjects compared to controls, but was significantly reduced after weight loss (p = 0.05). GFR also showed a non-significant tendency to decrease following loss of weight. Systolic and diastolic blood pressures were significantly decreased following weight loss (p less than 0.01 and p less than 0.025 respectively). In conclusion, although it is not possible to confirm the presence of true nephropathy in uncomplicated obesity, the latter can facilitate the onset of hemodynamic-type mechanisms which, in the presence of diabetes mellitus or arterial hypertension, may lead to the appearance of the nephrotic syndrome. PMID- 2098655 TI - [Psychometric evaluations in a group of obese patients]. AB - Several reported cases point out significant alterations in the psychologic profile of obese subjects and the utility of a psychotherapeutic support to the dietetic or pharmacological therapy. Each patient underwent a psychodiagnostic interview and the following rating-scales were applied: QPF (Psychophysiological Test); STAI X-1 and X-2 (State and Trait Anxiety Inventory); Hamilton-D (Depression); ZUNG (Self-administered Depression Test); TSR (Reaction Schemes Test). We observed an increase in the answer of the blocked projection (in the 40% of subjects), of negation (26.6%), of guilt (13.3%), a decrease in the projection answer (33.3%), high scores of QPF (21%). The STAI, the Hamilton, and the Zung were altered in the 10% of the examined subjects. Our data emphasize the importance of an individual psychotherapeutic support in a subgroup of obese subjects. PMID- 2098657 TI - [Fibrinogen and antithrombin III in obese subjects]. AB - The study aimed to evaluate the behaviour of two pre-thrombotic markers (hyperfibrinogenemia and hypoanti-thrombinemia) in obesity which is considered a factor of atherogenous risk. Ninety-three obese subjects were included in the study (29 M, 64 F, mean age 55 +/- 6, BMI 33 +/- 1), including 62 Type 2 diabetics. The following were assayed in each subject: glucose, total cholesterol, triglycerides (enzymatic method), fibrinogen (coagulometric method) and anti-thrombin III (chromogenic method). Results were assessed in relation to sex, age (0-50, 51-65, over 65), BMI (upto 30, 31-35, over 35), waist/hip ratio (upto 0.95, 0.96-1.02, over 1.02), cholesterolemia (upto 200, 201-250, over 250 mg%) and triglyceridemia (upto 150, 151-200, over 200 mg%). A significant increase (0.05) in fibrinogenemia was observed in the subjects aged between 51 65, with BMI above 35, with an intermediate waist/hip ratio (0.96-1.02) and with cholesterolemia over 250 mg%; reduced values of anti-thrombin III were found in subjects over 65 years old and with the lowest waist-hip ratio (upto 0.95); no significant data were obtained for the other parameters and for the correlation between fibrinogen and anti-thrombin III. The pro-thrombotic importance of hyperfibrinogenemia is underlined in obese subjects; this is proportional to age, to the degree of overweight and levels of cholesterolemia, even if equivocal results emerge with regard to the "android" variety. The reduction of anti thrombin III is correlated to senility and, surprisingly, to the gynoid-type waist/hip ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098656 TI - [No correlation between insulinemic levels and arterial hypertension in obese females]. AB - High blood pressure and impaired glucose tolerance are frequently associated with obesity: it has been suggested that hyperinsulinemia could represent one of the possible pathogenetic connections between obesity and systodiastolic hypertension. In order to verify this hypothesis we examined fasting and post load insulin and glucose levels in a group of 102 obese females, 58 hypertensive and 44 normotensive. All of the subjects underwent standard OGTT in order to measure their glycemic and insulinemic levels. No differences were found between two groups, as regard age and degree of obesity; blood pressure values were significantly different (p less than 0.01). No significative differences were detected for glycemic and insulinemic levels between hypertensive and normotensive subjects. These results indicate that hyperinsulinemia is not the prominent link between obesity and arterial hypertension; the relationship between these two conditions may be indirect. PMID- 2098658 TI - [Beta-endorphin and obesity. Possible pathogenetic implications]. AB - Several experimental data have documented the ability of both opiates and opioid peptides to stimulate food intake. On the other hand, the plasma beta-endorphin levels found in obese patients are higher than those observed in normal-weight controls, which may have pathogenetic implications. We have investigated the responses of plasma glucose, insulin, C-peptide and glucagon to an infusion of human beta-endorphin in formerly obese subjects who had obtained by dieting the normalization of body weight and in lean controls. The data show that: a) the increased plasma beta-endorphin concentrations found in human obesity are not corrected by normalization of body weight; b) formerly obese subjects behave as obese subjects in their metabolic and hormonal responses to beta-endorphin. PMID- 2098659 TI - [Insulin response to food in obese women]. AB - The effects of two standard meals (meal A: 20 g proteins, 20 g lipids, 80 g maltodextrin; meal B: meal A plus 52 g lipids) on insulin and C-peptide secretion and on plasma levels of glucose and free fatty acids (FFA) was studied in 12 obese women separated into two groups according to the onset of obesity. One group (n = 6) developed into obesity after puberty (OP), the other (n = 6) became obese after pregnancy (OG). Meals A.--In OP women, the maximum insulin response was reached at 30 min after meal (141.8 +/- 14.2 microU/ml) and insulinaemia fell to the basal values at 180 min; in OG women the insulin response was linear in the interval 30-150 min after meal. The maximum secretion of C-peptide occurred between 30 min and 90 min in OP and between 60 min and 120 min in OG; the secretion rate was similar in the two groups. Blood glucose levels returned to the basal values at 120 min after meal in OP and at 180 min in OG. FFA levels significantly decreased after meal in both groups (p less than 0.01 vs basal values). Meal B.--Insulin secretion was decreased at 30 min after meal in OP and at 150 min in OG and the levels of C-peptide was not modified in both groups. The glycaemic response was unchanged in OP, but was lower in OG women (p less than 0.02). These results show that OP women present stronger and more rapid insulin response to meals than the OG women; this conclusion is supported by the analysis of the secretion of C-peptide. Blood glucose levels return to basal values faster in OP than in OG women. The blood level of FFA after the standard meals A and B are normal both in OP and OG women. PMID- 2098660 TI - [Idiopathic hyperparathyroidism. Latent symptomatology and delay in diagnosis]. PMID- 2098661 TI - [Psychosocial aspects of the face and the dentition: an overview]. AB - On the basis of literature a description is given of the way people looked at body and face during history. Psychological and psychosocial consequences of physical (un-)attractiveness in general and of mouth and teeth in particular come up for discussion. Physical (un-)attractiveness seems to be of influence on the intellectual and emotional development and on the social relations of the individual. The findings lead to a theoretical model that can be used for further investigations on psychosocial effects of dental treatment within the departments of Special Dental Care. PMID- 2098663 TI - [Craniomandibular disorders. A retrospective study of patients referred to the department of Special Dental Care Utrecht]. AB - The data of 230 randomly selected patients were collected, constituting a representative sample out of the population visiting the department of Craniomandibular Disorders in Utrecht in 1987. By means of a flowchart an overview has been given concerning the intake of these patients and their course in diagnosis and treatment. Within the group of CMD-patients, four subgroups have been composed on basis of clinical and radiological findings. Differences have been found between these groups, concerning e.g. mean age and the prevalence of headache. Treatment results expressed as the clinical dysfunction index (objective) and the judgement of the patient (subjective) were found to be correlated. Most patients expressed mild symptoms of dysfunction after treatment. From the self-report questionnaire it can be concluded that the majority of the patients reported a satisfying treatment result. PMID- 2098662 TI - [Oligodontia]. AB - In every dental practice patients with oligodontia can be met. Oligodontia can occur solitary or as part of a syndrome. It is important for the dentist to be familiar with the various symptoms, including those of oligodontia as part of a syndrome. PMID- 2098664 TI - [Management of cleft patients]. AB - The primary closure of lip and palate gives spectacular results. The sequence and timing of the treatment afterwards can give rise to a conflict of interest. Speech development and maxillary growth are examples of this phenomenon. Some backgrounds are discussed on which management of the CLP treatment is chosen. The article ends with a management scheme divided in age categories. PMID- 2098665 TI - [Anxiety management of dental patients]. AB - The treatment of dentally anxious patients demands a behavioral approach, supported, if necessary, by pharmacological means. First of all coping is described. Next an overview is presented of the most common anxiety-reducing methods. To this goal the dentist has at his disposal: information, successive approximation, distraction and relaxation. Biofeed-back does not appear to be used. The systematic desensitisation, the deconditioning of dental anxiety, is dealt with separately, because this technique requires the aid of a psychologist. PMID- 2098666 TI - Explorations in the relationship of dream sleep to schizophrenia using positron emission tomography. AB - This study explored the relationship between rapid eye movement (REM) sleep and schizophrenia using positron emission tomography. Glucose use was compared between 49 schizophrenics, 30 awake controls and 12 controls in REM sleep. Assessment of the frequency and locations of brain areas showing significant differences suggested that REM did not resemble schizophrenia. Schizophrenics were between the higher awake controls and lower REM controls in corpus callosum glucose use. Hallucinating schizophrenics showed lower left caudate glucose use. PMID- 2098667 TI - Personality variables in depressed patients and normal controls. AB - Depressed patients (n = 46) were compared with normal controls (n = 42) for their scores on 7 personality variables measured on 4 personality questionnaires. The scores of the depressed patients obtained during the index depressive episode were significantly higher for introversion, neuroticism, and hostility, and significantly lower for self-esteem, than those of controls. Similarly, a subset of the female depressed patients studied when in remission and euthymic also had significantly higher socres than female controls for neuroticism and hostility, with a trend for significantly lower self-esteem scores. There were no significant differences on any of the 7 personality variables measured between depressed patients, with and without melancholia, or between patients with either unipolar or bipolar depression. PMID- 2098668 TI - Neuroendocrine and monoaminergic responses to acute administration of alprazolam in normal subjects. AB - The effect of a single dose (3 mg) of alprazolam on plasma cortisol, growth hormone (GH), prolactin, norepinephrine (NE) and 3-methoxy-4 hydroxyphenylethyleneglycol (MHPG) was studied in 10 healthy males. Alprazolam and placebo were administered orally in a crossover design and blood was sampled for 24 h. In comparison to placebo, alprazolam significantly reduced plasma cortisol levels and raised plasma GH levels. Prolactin levels were elevated by 100% from 2 to 8 h after alprazolam administration. The robust increase in prolactin levels is less consistent with previously reported data on traditional benzodiazepines. Plasma NE levels following alprazolam were lower than following placebo administration only at one time point, and MHPG concentrations were not affected. The lack of change in NE and MHPG levels suggests that the acute effect of alprazolam in normal subjects is not mediated via the central noradrenergic system. PMID- 2098669 TI - The dexamethasone suppression test in a group of research diagnostic criteria schizoaffective depressed men. AB - A dexamethasone suppression test (DST) was performed on 8 schizoaffective depressed men. Cross-sectional comparisons were made with three groups: schizophrenics (n = 10), unipolar major depressives (n = 23) and healthy controls (n = 43). All were drug-free and similar in age and body weight. Evaluations utilized the Research Diagnostic Criteria (RDC) for diagnosis, and the Hamilton Rating Scale for Depression for depressive symptom rating. DST nonsuppression, defined as a blood cortisol level of greater than or equal to 5.0 micrograms/dl at 16.00 h postdexamethasone, was observed in 43.5% of the major depressive disorder patients. This was different from the other three groups: 12.5% in schizoaffective depressed, 10.0% in schizophrenics and 9.3% in healthy controls (p less than 0.01, p less than 0.01, and p less than 0.001 respectively). Although schizoaffective depressed patients were significantly different from major depressive disorder patients in their DST responses, both groups were similar in their total HRSD scores and different from the schizophrenics (p less than 0.01 for each). These results, together with others previously reported by us on the thyrotropin-releasing hormone challenge in the same diagnostic groups, may be taken to mean that schizoaffective disorder, depressed type, is biologically distinct from major depressive disorder but not schizophrenia. On the other hand, until further corroborated, they should probably be considered a reflection of the heterogeneity of the schizoaffective syndrome and the nonspecificity of the DST. PMID- 2098670 TI - Risk factors for cardiovascular illness in panic disorder patients. AB - Supine and standing heart rate (HR) and blood pressure measures were compared among 19 nonsmoking normal controls, 29 smoking patients and 36 nonsmoking patients with panic disorder. The smoking patients had a significantly higher supine HR, standing diastolic blood pressure, standing mean blood pressure and supine and standing cardiac load measures compared to both patient nonsmokers and controls. There was no significant difference between controls and nonsmoking patients for any of the above measures except for the higher standing HR and the delta increase in HR upon standing in female panic disorder patients which suggests increased adrenergic activity. When lipid values of panic disorder patients (n = 92) were compared to National Reference Values for their sex and age for an increased risk of cardiovascular illness, there was no significant risk with regard to plasma levels of total cholesterol, high-density lipoprotein cholesterol or low-density lipoprotein cholesterol. PMID- 2098671 TI - Plasma tetrahydrobiopterin levels in patients with psychiatric disorders. AB - The plasma total biopterin and tetrahydrobiopterin (BH4) levels of 24 psychiatric patients were measured in the symptomatic phase, under no influence of psychotropic drugs as long as possible, and were compared with those of normal controls. The significant increase in total biopterin levels was observed only in the plasma of the patients with affective disorders or panic disorder in the depressive mood. A significant decrease in BH4 levels was observed only in the plasma of the patients with depression, and an increase in BH4 levels was observed only in the patients with hypomania. The changes of these biopterin levels in plasma could be a disease effect or a phase effect. PMID- 2098672 TI - Psychological effects of amantadine on psychotic subjects. AB - Psychotic subjects received amantadine in an open, naturalistic study. The psychological symptoms of the subjects were measured using the Brief Psychiatric Rating Scale. Some subjects experienced an increase in their symptoms. The subjects most likely to have the increase were those whose baseline level of functioning was most disturbed. PMID- 2098673 TI - Coffee-drinking and personality as factors in the genesis of cancer and coronary heart disease. AB - A study of the prediction of cancer and coronary heart disease on the basis of coffee consumption and personality shows that in cancer-prone probands (diagnosed on the basis of a personality inventory) coffee consumption was related to low incidence of cancer and high incidence of coronary heart disease, while diazepam showed the opposite trend. In coronary heart disease-prone probands coffee drinking was also linked with low incidence of cancer and high incidence of coronary heart disease, with diazepam again showing the opposite trend. In a personality type not prone to either disease, neither coffee consumption nor diazepam was linked with death from cancer or coronary heart disease. It is suggested that personality interacts in a predictable way with coffee and diazepam to determine in part the likelihood of death from cancer or coronary heart disease. Imipramine acts in a fashion similar to coffee, and opposite to diazepam. PMID- 2098674 TI - Effects of caffeine given before and after lunch on sustained attention. AB - Previous research has shown that caffeine increases alertness and improves sustained attention. In contrast to this, consumption of lunch leads to a decline in the ability to maintain attention. The main aim of the present study was to determine whether caffeine removes or reduces the postlunch drop in performance, an issue which is of considerable practical importance and theoretical interest. The results showed that caffeine improved performance on the Bakan vigilance task and removed the post-lunch dip observed in the decaffeinated condition. Similar effects were observed in one of the conditions of a mental rotation task. The lunch X caffeine interaction observed in the Bakan task did not change over the course of the task. In contrast to the performance data, lunch X caffeine interactions were not observed in analyses of cardiovascular function or subjective mood. PMID- 2098675 TI - Epileptic attack, delirium, and a Creutzfeldt-Jakob-like syndrome during mianserin treatment. AB - Our report concerns 2 patients who developed delirium after an epileptic attack during mianserin treatment. In both cases the EEG showed a change with periodic sharp slow complexes similar to that seen in Creutzfeldt-Jakob disease. The symptoms subsided, however, and the EEG normalized after the antidepressant was discontinued, suggesting a noxious response to mianserin. If Creutzfeldt-Jakob like changes in the EEG occur, the possible effect of antidepressant medication should be considered. PMID- 2098676 TI - High-potency sweeteners and dental health. PMID- 2098677 TI - Not so equal increase in female and minority dental students and graduates. PMID- 2098678 TI - Terminating a dentist-patient relationship without creating legal or ethical problems. PMID- 2098679 TI - Interplay between dental and legal ethics during a professional liability case. PMID- 2098680 TI - Issues and traits that influence dentists' professional satisfaction and economic success. PMID- 2098681 TI - Rapidly growing nodule of the lower lip. PMID- 2098682 TI - Multiple mucosal lesions in a patient with candidiasis. PMID- 2098684 TI - [Mastication, support and basic relations of dental occlusion in practice]. PMID- 2098683 TI - [Rational and sure way of making complete dentures]. PMID- 2098685 TI - Goods and services. Tax summary. PMID- 2098686 TI - International investing. Questions and answers. PMID- 2098687 TI - Efficacy of plax prebrushing rinse in reducing dental plaque. PMID- 2098688 TI - Protecting your estate. PMID- 2098689 TI - Information. It's power, it's important and it's addictive. PMID- 2098690 TI - Setting the standards. California keeps the public informed. PMID- 2098691 TI - Results of marketing. Institutional advertising is a reality and a success in Quebec. PMID- 2098692 TI - Dental awareness campaigns. A focal point for the 90s. PMID- 2098693 TI - Trial by media. Scrutiny of the popular press. PMID- 2098696 TI - [Outcome of focal therapy in dentistry]. PMID- 2098694 TI - Prebiotic synthesis of orotic acid parallel to the biosynthetic pathway. AB - By heating an aqueous solution of aspartic acid and urea, carbamylaspartic acid is first formed and then the molecule is cyclized to dihydroorotic acid (DHO) with loss of water. Irradiation of an aqueous solution of DHO with a tungsten lamp yields orotic acid by photo-dehydrogenation of the molecule. This pathway of orotic acid formation is quite similar to that of biosynthesis of the molecule. PMID- 2098695 TI - A statistical theory of amino acid mutation. AB - Assuming that the observed mutation frequency of an amino acid depends on two factors. The first is mutation coefficient which describes the rate of the nucleotide substitution stochastically and the second is the similarity of amino acids which represents the fitness of a mutant under the selective pressure. A statistical theory is proposed and 380 mutation frequencies are calculated, only 10 of which disagree obviously with the observed data. PMID- 2098697 TI - Effect of Actinobacillus actinomycetemcomitans, Wolinella recta and Bacteroides gingivalis on the viability of retinoic acid-induced and dimethyl sulfoxide induced HL-60 cells. AB - We studied the interactions between viable and heat-killed, opsonized and unopsonized periodontopathic bacteria with both uninduced and induced HL-60 promyelocytic leukemia cells. The cells were induced to differentiate into granulocyte-like cells by incubation with retinoic acid (RA) or dimethyl sulfoxide (DMSO). When unopsonized, Wolinella recta ATCC 33228 significantly suppressed the net proliferation of uninduced HL-60 cells, Actinobacillus actinomycetemcomitans strain Y4 was markedly lethal to the cells, and Bacteroides gingivalis ATCC 33277 had no effect. Unopsonized and opsonized A. actinomycetemcomitans and W. recta had equally potent lethal effects on induced HL-60 cells. Unopsonized B. gingivalis was not lethal to the induced cells in the dose used (100 bacteria/HL-60 cell), but opsonized B. gingivalis was lethal, especially in the first 24 h. The killing effects of A. actinomycetemcomitans and W. recta were largely eliminated if they were heated (56 degrees C, 30 min) before being added to the induced HL-60 cells. RA-induced HL-60 cells were more sensitive to the lethal effects of A. actinomycetemcomitans and W. recta than were DMSO-induced cells. The results suggest that the HL-60 cell line may be a useful model for studying granulocyte-bacteria interactions. PMID- 2098698 TI - Interaction of gram-negative periodontal pathogens with retinoic acid-induced and dimethyl sulfoxide-induced HL-60 cells. AB - As a first step toward elucidating the reasons for differences among periodontal pathogens in their cytotoxic effects on HL-60 cells, we used transmission electron microscopy to examine morphological aspects of granulocyte-bacteria interactions. Unopsonized Actinobacillus actinomycetemcomitans strain Y4 and Bacteroides gingivalis ATCC 33277 adhered to, and were phagocytosed by, retinoic acid-induced and dimethyl sulfoxide-induced HL-60 cells. In contrast, there was only minimal interaction between Wolinella recta ATCC 33238 and these induced granulocyte-like cells. Only isolated examples of adherence of W. recta to HL-60 cells were seen. In specimens prepared for routine transmission electron microscopy, ingested W. recta were not observed. In immunogold experiments, phagocytosed W. recta were noted, but only rarely. Opsonization of A. actinomycetemcomitans, B. gingivalis and W. recta with specific antisera appeared to increase their level of interaction with the HL-60 cells. We suggest that the HL-60 cell line may be useful in elucidating structure-function relationships between human neutrophil-like cells and putative periodontopathogens. PMID- 2098699 TI - Lipopolysaccharide from Actinobacillus actinomycetemcomitans stimulates macrophages to produce interleukin-1 and tumor necrosis factor mRNA and protein. AB - Actinobacillus actinomycetemcomitans is associated with periodontal disease in children and adults. We report that low concentrations of lipopolysaccharide (LPS) from A. actinomycetemcomitans stimulated human macrophages to increase dramatically their accumulation of mRNA coding for interleukin-1 alpha (IL-1 alpha), IL-1 beta as well as tumor necrosis factor (TNF). Protein levels of IL-1 and TNF alpha also increased. Levels of these mRNAs increased by 4-5 fold as compared with unstimulated macrophages when these cells were cultured with as little as 2 ng/ml LPS from A. actinomycetemcomitans. Polymyxin binds and blocks the action of LPS; polymyxin inhibited the ability of LPS from A. actinomycetemcomitans to increase levels of IL-1 beta mRNA. The LPS of A. actinomycetemcomitans stimulated increased levels of IL-1 beta mRNA in the presence of cycloheximide, showing that stimulation by this LPS did not require new synthesis of protein. Furthermore, dexamethasone inhibited the ability of LPS from A. actinomycetemcomitans to stimulate the accumulation of mRNA coding for IL 1 beta. A. actinomycetemcomitans is an invasive microorganism of the gingiva; high intragingival numbers correlate with sites undergoing local destruction of the periodontium. IL-1 alpha, IL-1 beta, and TNF are potent monokines that mediate inflammation and resorption of bone. Out studies suggest that macrophages migrating to these gingival sites of A. actinomycetemcomitans infection will be stimulated by LPS of A. actinomycetemcomitans to produce IL-1 alpha, IL-1 beta and TNF. These cytokines will mediate gingival inflammation and stimulate resorption of alveolar bone. PMID- 2098700 TI - Effect of iron limitation on Bacteroides gingivalis. AB - This study was undertaken to describe the effects of iron limitation on Bacteroides gingivalis. Four strains of B. gingivalis were grown in brain heart infusion broth, substituting protoporphyrin IX for hemin. Culture with protoporphyrin IX resulted in a loss of a 28 kDa membrane protein, but no decrease in growth. Iron-restricted cultural conditions for the growth of B. gingivalis were achieved using alpha/alpha'-dipyridyl, a ferrous iron chelator, at concentrations from 12.5 microM to 300 microM. Total suppression of bacterial growth for strain A7A1-28 and strain 381 was achieved at 200 microM alpha/alpha' dipyridyl. At 300 microM alpha/alpha'-dipyridyl, strain W50 and Bowden 18/10 showed 100% and 80% suppression of growth, respectively. The ferric iron chelator Desferal did not show suppression of growth in concentrations up to 500 microM. The dipyridyl inhibition of cell growth for strain A7A1-28 could be reversed by adding excess ferrous ammonium sulphate but not by ferric nitrate. Iron regulation of proteolytic enzymes could not be demonstrated. Two new membrane proteins 42 kDa and 24 kDa are expressed with iron limitation, and the 45 kDa membrane protein was decreased with iron limitation. PMID- 2098701 TI - Haemagglutinating and haemolytic activity of the extracellular vesicles of Bacteroides gingivalis W50. AB - The extracellular vesicles (ECV) and extracellular protein (EP) fractions of Bacteroides gingivalis W50 showed haemagglutinating (HA) activity towards sheep erythrocytes. Similar fractions from the nonpathogenic strain W50/BE1 did not haemagglutinate. W50 ECV HA activity was not inhibited by various glycosidase, phospholipase or protease pretreatments, sugars or amino acids, including arginine or lysine. The haemagglutinating activity of ECV was associated only with the extracellular vesicle membrane. The EP and ECV of both strains displayed haemolytic activity. This activity was apparently depressed in the presence of 10 mM dithiothreitol (DTT). All EP and ECV fractions degraded certain structural sheep erythrocyte membrane proteins. The greatest activity was displayed by W50 ECV and W50/BE1 EP and was enhanced by DTT. In the presence of DTT, the ECV of both strains degraded purified human haemoglobin but this activity was greatly reduced in its absence. PMID- 2098702 TI - Benzoyl-arginine naphthylamide (BANA) hydrolysis by Treponema denticola and/or Bacteroides gingivalis in periodontal plaques. AB - Treponema denticola and Bacteroides gingivalis are among the few recognized species found in periodontal pockets that can hydrolyze the synthetic peptide N benzoyl-DL-arginine-2-naphthylamide (BANA). We determined the presence of these periodontal pathogens in BANA-positive and -negative plaque samples through the use of indirect immunofluorescent antibody techniques. Eighteen of 27 diseased sites gave BANA-positive reactions, and 9 gave BANA-negative reactions. T. denticola was present in 16 of 18 BANA-positive reactions, whereas B. gingivalis was detected in 9 of the 18 BANA-positive reactions. T. denticola was present in 1 and B. gingivalis in 2 of the 9 BANA-negative reactions. Neither organism was detected in the 19 healthy sites that were negative for BANA. All measured differences between BANA-positive and BANA-negative plaques obtained in the same individuals were statistically significant. The accuracy of the BANA test, compared with clinical parameters such as bleeding upon probing and increased probing depth, was about 80%. The accuracy of the test in detecting the presence of T. denticola was 93%, for B. gingivalis, 76% and for T. denticola and/or B. gingivalis, 96%. This study indicated that BANA-positive plaques were associated with the presence of T. denticola and/or B. gingivalis, that T. denticola was found at a greater frequency and levels in BANA-positive plaques than B. gingivalis, and that the presence of these organisms was associated with clinical disease. PMID- 2098703 TI - Maintenance of proton motive force by Streptococcus mutans and Streptococcus sobrinus during growth in continuous culture. AB - The components of the transmembrane electrochemical proton gradient, or proton motive force (PMF, delta p), were determined in cells of Streptococcus mutans Ingbritt and Streptococcus sobrinus ATCC 27352 growing in continuous culture under conditions of changing glucose concentration, growth rate and growth pH. The pH gradient (delta pH) and membrane electrical potential (delta psi) were assayed with the weak acid, salicyclic acid, and the lipophilic cation, methyltriphenylphosphonium iodide, respectively. S. mutans Ingbritt growing in continuous culture (pH 7.0, dilution rate (D) = 0.1 h-1) at 8 glucose concentrations ranging from 2.8 to 288 mM maintained a relatively constant delta p of 58.3 mV (SD +/- 5.8) in spite of a transition from glucose to nitrogen limited growth and significant changes in cell physiology. Changes included a decreasing yield constant, increasing glucose uptake rates in the chemostat, repression of Ellglc of the PEP phosphotransferase sugar transport system and decreasing glycolytic capacity of the cells as the medium glucose concentration increased. Changes in the dilution or growth rate of S. mutans Ingbritt from 0.1 to 1.0 h-1 and S. sobrinus from 0.1 to 0.8 h-1, when growing at pH 7.0 with limited glucose and lactose, respectively, resulted in significantly lower delta p values due to the dissipation of the delta psi. When the cells of S. mutans Ingbritt were grown with excess glucose (nitrogen limitation), lower delta p values were observed at pH 5.5, but not at pH 7.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098704 TI - A IIIman protein is involved in the transport of glucose, mannose and fructose by oral streptococci. AB - We show in this article that the transport of glucose, mannose and fructose by the phosphoenolpyruvate: mannose phosphotransferase system of oral streptococci requires the participation of a protein component that we have called IIIman. This protein was purified from Streptococcus salivarius by chromatography on DEAE cellulose, DEAE-TSK, hydroxyapatite, and Dyematrex Green A. The purified protein migrated as a 38,900 molecular weight protein on a sodium dodecyl sulfate polyacrylamide gel. However, electrophoretic analysis of phosphoproteins and Western blot experiments indicated the presence in membrane-free cellular extracts of S. salivarius of 2 different forms of IIIman having molecular weights of 38,900 and 35,200. The presence of the high-molecular-weight form of IIIman was observed by immunodiffusion, Western blot and phosphorylation by [32]PEP in S. salivarius, Streptococcus mutans, Streptococcus sobrinus, and Streptococcus lactis but not in Streptococcus faecium, Staphylococcus aureus, Bacillus subtilis and Lactobacillus casei. Antibodies directed against the IIIman of S. salivarius did not react with the IIIman of Escherichia coli. PMID- 2098705 TI - In vitro antimicrobial sensitivity of enteric rods and pseudomonads from advanced adult periodontitis. AB - The prevalence and in vitro antimicrobial sensitivity of isolates of enteric rods and pseudomonads was examined in 844 adult periodontitis patients. These organisms were recovered from 13.5% of the study subjects. Ciprofloxacin exhibited the highest inhibitory activity of the 14 oral antimicrobial agents tested. Beta-lactam antibiotics were largely ineffective, and tetracycline failed to inhibit most Pseudomonas species. In vitro sensitivity data suggest that a subgingival microbiota comprising mainly streptococci would result from therapy that combined ciprofloxacin and metronidazole. Since streptococci may inhibit the growth of several putative periodontal pathogens, populations of "beneficial" streptococci in the periodontal pocket might constitute a very attractive therapeutic outcome. Controlled clinical studies are needed to clarify the possible role of ciprofloxacin in the treatment of destructive periodontitis. PMID- 2098706 TI - Immunoreactivity in humans of Bacteroides gingivalis hemagglutinating adhesin HA Ag2. AB - A rabbit antiserum monospecific for HA-Ag2, a hemagglutinating adhesin of Bacteroides gingivalis, was used as a reference to screen sera from 8 patients with chronic periodontitis and 6 normal subjects for specific antibodies. The monospecific antiserum detected a complex of 2 polypeptides with molecular weights of 43 and 49 kDa in an outer membrane preparation of B. gingivalis. All human sera reacted with one or both polypeptides in at least one of the isotypes (IgG, IgA and IgM) tested, indicating that HA-Ag2 is an immunodominant antigen. Although the 2 components of HA-Ag2 are antigenically similar, a trend toward preferential reactivity of IgM with the 49 kDa component was observed. This suggests that an epitope-specific mechanism of regulation of the immune response to B. gingivalis in humans may exist via the HA-Ag2 complex. PMID- 2098707 TI - Age and sex relationships of superinfecting microorganisms in periodontitis patients. AB - The occurrence by age and sex of subgingival enteric rods and pseudomonads, yeasts, and staphylococci was studied in 3075 "refractory" periodontitis patients referred for microbiological analysis. Each subject contributed a pooled subgingival sample obtained from 3 deep periodontal pockets with paper points. Selective and nonselective media and commercial identification kit systems were used for microbial isolation and speciation. Females constituted about 60% of the study subjects, and almost one-third of all patients were in their forties. Females (47.3%) showed a higher prevalence of the study organisms than males (43.9%). Older females (15.9%) and males (15.3%) revealed significantly higher prevalences of enteric rods and pseudomonads than younger individuals (10.9%), and older infected females yielded significantly higher viable counts than younger infected females. The sexes demonstrated a similar prevalence of staphylococci (about 28%), but younger infected females and males showed significantly higher viable counts than older infected individuals. No sex or age relationships were found for yeasts (about 14% of individuals infected). The high level of subgingival enteric rods and pseudomonads in some individuals may be important in the pathogenesis of geriatric and other forms of periodontitis and may have therapeutic implications. PMID- 2098708 TI - Dental caries in congenitally athymic rats. AB - The importance of the immune response in dental infection was evaluated in heterozygous (rnu/+) normal and homozygous (rnu/rnu) congenitally athymic "nude" Rowett rats. Animals of both types were infected, or immunized and infected, with mutans streptococci (Streptococcus sobrinus strain 6715). The mean numbers of S. sobrinus cells recovered from the nude rats were higher than those from comparable (immune/nonimmune) normal rats in 10 of 12 possible comparisons. Also, S. sobrinus constituted a greater percentage of the total streptococci in the nude rats compared with normal animals (6 of 6 possible comparisons). Antibody to S. sobrinus whole cells or to S. sobrinus glucosyltransferase from nude rats in serum or in saliva was significantly lower (or absent) than that of comparable normal rats. This was seen after infection, but was most pronounced after immunization (and infection). Dental caries was also significantly elevated in the congenitally athymic animals. Immunologic deficiency of congenitally athymic rats can lead to a greater infection level with mutans streptococci and increased dental caries. PMID- 2098709 TI - Killing of oral, gram-negative, facultative bacteria by the rabbit defensin, NP 1. AB - Oral, gram-negative, facultative bacteria, including Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Capnocytophaga spp. have been associated with destructive periodontal infection. Neutrophils play a critical role in defending the periodontium against destructive infection. Defensins are antimicrobial peptides that have been isolated in human, rabbit, guinea pig, and rat leukocytes that may constitute an important nonoxidative mechanism of killing. The purpose of this study was to examine the sensitivity of a battery of oral, gram-negative, facultative bacteria to the bactericidal effects of the isolated rabbit peptide NP-1. All species tested were killed by NP-1; however, there was strain-to-strain variation in sensitivity. The bactericidal effect was not dependent on net bacterial growth, although metabolic activity was evident as assessed by bacterial oxygen consumption. We conclude that bacteria are sensitive to the cidal mechanism involved in defensin-mediated bacterial killing and that the conditions of this assay system support the killing of bacteria by the defensin peptides. PMID- 2098710 TI - Distribution and frequency of Fusobacterium nucleatum subspecies in the human oral cavity. AB - Three reference strains of Fusobacterium nucleatum and 32 human oral isolates were compared by a variety of physiological tests, enzyme electrophoretic profiles, SDS-PAGE patterns, DNA base composition and hybridization to test their possible site specificity and frequency of the recently described subspecies of F. nucleatum. Nine of the 11 isolates assigned to F. nucleatum subspecies nucleatum were from diseased sites, whereas isolates from healthy sites were all identified as F. nucleatum subspecies polymorphum or F. nucleatum subspecies fusiforme. Strains of the latter subspecies were the least frequently isolated (2 of 32). These results, although still inconclusive because of the relatively small sample size, nevertheless confirmed the heterogeneity of F. nucleatum and indicate that most human oral isolates from subgingival sites probably belong to F. nucleatum subspecies nucleatum. PMID- 2098711 TI - pH-dependent fluoride inhibition of catalase activity. AB - The inhibitory effects of fluoride on several catalases were examined over a range of pH conditions. Preparations of bovine-liver catalase were sensitive to fluoride under acidic conditions. Catalase activity associated with whole-cell preparations of Actinomyces viscosus NP 311A remained relatively constant between pH 3.0 and 8.0 and was inhibited by fluoride in a pH-dependent manner. Fluoride was also observed to enhance hydrogen peroxide killing of A. viscosus NP 311A under acidic pH conditions. Results suggest that some catalase enzymes, including those associated with common plaque bacteria, may be inhibited by fluoride in a pH-dependent manner. PMID- 2098712 TI - Black-pigmented, asaccharolytic Bacteroides species resembling Porphyromonas gingivalis (Bacteroides gingivalis) from beagle dogs. AB - Black-pigmented, asaccharolytic Bacteroides strains, which positively reacted with anti-Bacteroides gingivalis (now reclassified as Porphyromonas gingivalis) serum, were isolated from beagle dogs, and their characteristics were studied and compared with those of P. gingivalis. The strains from dogs were different from P. gingivalis in their catalase activity, nutritional requirements and oxygen tolerance, and double-immunodiffusion tests showed serological dissimilarity between the strains from dogs and P. gingivalis. However, the strains from dogs had guanine-plus-cytosine contents of 49.0 to 49.3 mol %, which were very similar to P. gingivalis, and they showed strong DNA-DNA hybridization with P. gingivalis. These results indicated that beagle dogs had Porphyromonas species analogous to P. gingivalis in their oral cavities. PMID- 2098713 TI - Role of pH in salivary histidine-rich polypeptide antifungal germ tube inhibitory activity. AB - Purified synthetic salivary histidine-rich polypeptides (HRPs) 2, 3, 4, 5 and 6 were found to inhibit Candida albicans conversion of blastospores to germ tubes. HRP-4 was the best inhibitor within the pH 5 to 7 range tested and all of the HRPs were observed to lose potency as the pH was raised from 5 to 7. The pH pattern obtained with a synthetic homologous histidine peptide suggested that the protonated form of the histidine imidazole residues of the HRPs was important to the germ tube antifungal activity. Similar pH inhibition profiles of germ tube formation by parotid saliva and the HRPs were also observed. PMID- 2098714 TI - Antimicrobial activities of thiolactomycin against gram-negative anaerobes associated with periodontal disease. f1. AB - Thiolactomycin (TLM), (4R)-(2E,5E)-2,4,6-trimethyl-3-hydroxy-2,5, 7-octatriene-4 thiolide, purified from a culture filtrate of a strain of the Nocardia species, was examined for antimicrobial activities against more than 100 strains of oral and periodontally associated bacteria. Nine other commonly used antibiotics were also included for the test. We found that TLM exhibited strong and selective antimicrobial activities against Bacteroides gingivalis and other oral black pigmented Bacteroides species that may be etiologically associated with adult periodontitis. TLM also inhibited the growth of Actinobacillus actinomycetemcomitans, but did not affect the growth of oral streptococcal species and Eubacterium species. Strains of Eikenella corrodens were moderately susceptible to TLM, while Actinomyces viscosus strains were only slightly susceptible to it. Other antibiotics used for comparison showed a broad spectrum of antimicrobial activities in general. In conclusion, TLM exhibited highly selective antimicrobial activities to black-pigmented Bacteroides species and A. actinomycetemcomitans, both of which are implicated in the pathogenesis of human periodontal disease. PMID- 2098715 TI - Association of selected bacteria with the lesions of root surface caries. AB - Plaque from the root surfaces of 165 subjects (mean age 65.5 years, 22-26 teeth/subject) was analysed for specific bacteria. Five subject groups were defined: A (DMFS 16.4), B (DMFS 55.9), C1 (DMFS 55.6), C2 (DMFS 57.0) and C3 (DMFS 48.1). Groups C1 and C2 had unrestored root surface lesions; Group A, B and C3 were free of unrestored root caries and differed in their coronal caries experience. Streptococcus mutans was isolated more frequently from the root lesions in Groups C1 and C2 than from intact root surfaces in Group A. Streptococcus oralis, Streptococcus mitis 1 and Streptococcus sanguis were isolated more frequently from Group A. The percentage contribution that S. mutans made to plaque from lesions in Groups C1 and C2 was higher than that from plaque in Group A and Actinomyces viscosus serovar 2 contributed more to plaque in Group C1 than in samples from Group A. The percentage counts of Lactobacillus in plaque from lesions in Groups C1 and C2 were higher than those from intact roots in Groups A, B, and C3. Subjects were also grouped on the presence of Lactobacillus and S. mutans in plaque samples. Samples with both organisms (n = 17) showed significantly higher isolation frequencies of specific strains of S. mitis 1 and also A. viscosus serovar 2 compared with samples of plaque containing S. mutans or Lactobacillus. Actinomyces naeslundii serovar 1 was not isolated from samples containing both S. mutans and Lactobacillus. The results confirm an association of S. mutans and Lactobacillus with root surface lesions and suggest a relationship between lesions and A. viscosus serovar 2. PMID- 2098716 TI - Control of sugar utilization in oral streptococci. Properties of phenotypically distinct 2-deoxyglucose-resistant mutants of Streptococcus salivarius. AB - The physiological and biochemical characterization of Streptococcus salivarius mutants isolated by positive selection for resistance to 0.5 mM 2-deoxyglucose in the presence of lactose are reported. We found 2 classes of mutants following a series of experiments that included: growth rate determinations, uptake studies, measurement of phosphotransferase system (PTS) activities and detection of the IIIman proteins by Western blotting and analysis of [32P]PEP-phosphorylated proteins. Class 1 mutants did not possess the low-molecular-weight form of IIIman. They did not grow on mannose and were unable to transport 2-deoxyglucose. On the other hand, class 2 mutants possessed the 2 forms of IIIman, grew readily on mannose and transported 2-deoxyglucose, albeit at a lower rate than the parental strain. Both classes of mutants exhibited abnormal growth in media containing mixtures of sugars. Moreover, derepression of genes coding for catabolic enzymes was observed in all the mutant strains. Our data suggested that the role of the mannose PTS in the control of sugar utilization in S. salivarius is complex and may involve the participation of several components. PMID- 2098717 TI - Purification and characterization of a 43-kDa protease of Bacteroides gingivalis. AB - From the culture supernatant of Bacteroides gingivalis ATCC 33277, a thiol protease was purified to homogeneity by fractional ammonium sulfate precipitation, ion-exchange chromatography, gel filtration, and isoelectric focusing. Its molecular weight was 43 kDa and showed similar enzymatic properties to a 300-kDa protease that was previously characterized. PMID- 2098718 TI - [New criteria for secondary decay and marginal defects]. AB - The survival time of restorations and the reasons for replacements vary considerably from one study to another. Different studies report that secondary caries alone accounts for 0-60% of the reasons. Great variations in treatment planning have been reported when dentists examine the same restorations. Different diagnostic criteria and treatment strategy are probably responsible for most of the variations. In this article specific criteria for secondary caries and marginal defects are presented. PMID- 2098719 TI - [Systems for grading occlusal and approximal carious lesions]. AB - Well defined, graded caries diagnoses are necessary for recording caries and its progression, measurement of the efficacy of caries prophylaxis, and for the establishment of detailed information concerning the prevalence of caries. Monitoring of the severity of lesion or degree of caries should be based on well defined, reliable clinical or radiographical findings. Such criteria for occlusal and approximal caries are presented in this paper. PMID- 2098720 TI - [Genetics--a challenge. 2. Use of genetic techniques in clinical dentistry and research]. PMID- 2098721 TI - [Dental anxiety and social stratification]. AB - Self-reported dental anxiety in relation to sociocultural and socioeconomic variables were investigated in a random sample of the Norwegian population aged 15 years and older (n = 1351). Education, profession, number of years in school, family income and personal income were negligibly or not at all associated with dental anxiety. The only statistically significant difference in levels of self reported dental anxiety in relation to social background factors was between female labourers (high level) and female functionaries (low level). PMID- 2098722 TI - [Simple model explaining the caries inhibiting effect of fluoride]. AB - The pH at which enamel dissolves is affected by presence of fluoride in the plaque fluid. It appears that the degree of oral hygiene will also be important because pH can drop so low in old plaque that even solid fluorapatite dissolves. Improved oral hygiene would thus reduce caries in high risk patients even in the presence of fluoride. PMID- 2098723 TI - [Root caries in a patient population in northern Norway]. AB - The prevalence of root caries in an adult population of patients (n = 254) admitted to treatment in a private dental practice was recorded according to Katz RCI-index. Mean RCI in the whole group was 22.6, for those with exposed root surface 32.4. Users of partial denture had a mean RCI about twice as large as non users. PMID- 2098724 TI - Comparison of glass-ionomer cements used to repair cast restorations. AB - Based on SEM analysis, this study evaluates the usefulness of three glass-ionomer cements to repair margins of cast restorations. These findings are compared to those previously obtained for amalgam, resin, and direct gold used as repair materials. This information can assist the clinician in choosing the most appropriate repair material in selected cases. PMID- 2098725 TI - Contraction patterns in cavities tested with two dentin bonding agents. AB - Differences in microleakage at occlusal and cervical margins have been attributed to variations in the microstructure of enamel. The lack of homogeneity in dentin may have similar influences on the effectiveness of composite bonding. This study examined marginal contraction gaps occurring at the occlusal, cervical, mesial, and distal margins of dentin cavities restored with a composite restorative material, with and without the use of dentin bonding agents. Results showed that marginal contraction gaps at the dentin-restoration interface among the four sites in both treated and untreated cavities are not statistically different in size. Adhesion of composite restorative materials to dentin is not affected by the location of the margins. PMID- 2098726 TI - Effect of dentinal pretreatment on bond strength between glass-ionomer cement and dentin. AB - Removal of the dentinal smear layer prior to placement of glass-ionomer cement is thought to maximize the strength of glass-ionomer cement/dentin bonding. This study evaluated the effect of three polyacrylic acid pretreatments on bond shear strength between glass-ionomer cement and dentin. Extracted human molars were divided into four groups of 30 specimens each. One group (the control) received no pretreatment. Specimens in the remaining groups were pretreated with one of three commercially available polyacrylic acid conditioners, used according to the manufacturers' recommendations. The results indicated significant differences in shear strength among pretreatment conditions. Since the manufacturers' recommendations varied, it is not clear if these results were due to differences in polyacrylic acid concentration or to other factors, such as application time or placement procedure. PMID- 2098727 TI - Lesions in vitro associated with a Fl-containing amalgam and a stannous fluoride solution. AB - Secondary caries is one of the most important factors leading to replacement of amalgam restorations. This investigation compared the anticariogenic effect of a fluoride-containing amalgam, a stannous fluoride application in the cavity prior to restoration with conventional amalgam, and the combination of the fluoride treatment with the well-recognized technique of cavity varnishing. Class 5 cavities were prepared in the middle third of both buccal and lingual surfaces of 20 extracted premolars. Conventional amalgam was inserted in 10 cavities (control group). Fluoride-containing amalgam was inserted in 10 cavities (second group). The third group received a treatment of 8% SnF2 and the fourth group received the SnF2 and a cavity varnish application before insertion of the conventional amalgam. After 15 weeks in an acid-gel for caries-like lesion formation, the teeth were sectioned longitudinally and examined with polarized light. The results showed that both fluoride-containing amalgam and conventional amalgam with prior treatment of the cavity with the stannous fluoride solution and varnish had an inhibitory effect on the development of artificial cavity wall caries in vitro. PMID- 2098728 TI - Reducing microleakage with the glass-ionomer/resin sandwich technique. AB - The effect on microleakage of two glass-ionomer/resin "sandwich" restorations and an incrementally placed microfilled resin restoration was tested in class 5 preparations extending apical to the cementoenamel junction. There was significantly less leakage detected in the sandwich restorations with microfilled resin placed in one or two increments. These results indicate that a glass ionomer/microfilled resin sandwich restoration may significantly reduce microleakage in restorations extending below the cementoenamel junction. PMID- 2098729 TI - Sensitivity study in vivo: glass-ionomer versus zinc-phosphate bases beneath amalgam restorations. AB - This study in vivo evaluated the sensitivity of class 1 and 2 amalgam restorations which had bases of either zinc phosphate or an admix, silver reinforced glass ionomer. The evaluation of sensitivity was done by providing the patient with five postcard questionnaires to be mailed to the clinic over a period of time from one to 28 days. Teeth restored with amalgam and silver reinforced glass ionomer were significantly less sensitive to cold than those restored with amalgam and zinc phosphate. PMID- 2098730 TI - [Allergy to antibiotics other than penicillin]. PMID- 2098731 TI - [Incidence of antigen expression for HLA antigens A,B,C and DR in patients with atopic diseases in Poland]. AB - Studies of several authors suggest an interdependence of atopic diseases and HLA antigens. Therefore, the authors evaluated an incidence of HLA antigens of classes I and II in patients with atopic disease and healthy individuals. The study involved 127 patients with atopy and 79 healthy blood donors. Anamnesis, results of skin tests and serum levels of allergenic-specific IgE served as the base of atopy diagnosis or exclusion. HLA antigens were assayed with a standard micro-lymphocytotoxic test using two series of standard anti-HLA sera. It enabled to detect 16 locus A-dependent antigens, 25 locus B-dependent and 8 locus C dependent antigens as well as 8 antigens dependent on locus DR. Only antigen HLA Bw53 was found more frequently in patients with atopic diseases suggesting its relation to atopy. The results concerning other HLA antigens did not confirm HLA antigens association with atopy suggested by other authors. PMID- 2098732 TI - [Epidemiologic studies on allergic diseases among rural and urban school children in Poland]. AB - 451 rural children (group I) and 2000 urban children (group II) aged 10-16 years from Torun province were inquired by a questionnaire to their parents or guardians. 9.09% of children in the country and 13.45% of those living in the city of Torun suffered from hypersensitivity disorders; bronchial asthma was reported in 2.22% and 3.05% of cases, allergic rhinitis--in 3.77% and 7.15%, allergic conjunctivitis--in 1.33% and 2.75%, allergic edema--in 0.44% and 0.60%, urticaria--in 1.55% and 3.50%, and infantile eczema--in 0.44% and 2.10% of cases, respectively. The pollinosis prevalence rate was 2.00% in group I and 1.85% in group II. At least 2 various forms of hypersensitivity coexisted in 30.48% of allergic urban children (64.86% of patients with pollinosis among them); infantile eczema preceded allergic rhinitis and bronchial asthma symptoms in 6.29% and 11.47% of cases, respectively, while allergic rhinitis occurred before the onset of bronchial asthma in 24.59% of asthmatic children. 37.10% of individuals with positive family history of allergic conditions also fell ill with some diseases of this nature, while in those with negative family history allergy occurred only in 10.22% of cases. From environmental factors mother's diseases during pregnancy, bottle feeding and a regular diet during the first year of life, frequent respiratory infections in the early childhood and poor living conditions increased the risk of allergic diseases or aggravated their course in the population examined. PMID- 2098733 TI - [Sensitivity to mugwort pollen allergens (Artemisia vulgaris)]. AB - The author has found that 42% of patients with pollinosis had positive skin reactions with mugwort (Artemisia vulgaris) pollen allergens. The majority of tested patients (139 out of 187) were also allergic to grass pollens. However, hypersensitivity to mugwort pollen allergens was isolated and did not accompany grass pollen allergy. The symptoms of pollinosis appeared in this group later than in patients sensitive to grass pollen allergens only (over 21 years of age in 71%). Bronchial asthma was diagnosed in 40% of these patients and allergic skin reactions in 25%. Sensitivity to mugwort pollen allergens was accompanied by the sensitivity to pollen allergens of Graminae family of plants in 80% of cases. The author suggests that sensitivity to mugwort pollen allergens is the second most frequent cause of the pollinosis and is diagnosed too rarely. Failures of desensitization in patients sensitive to pollen allergens of Graminae family of plants may often result from coexisting sensitivity to mugwort pollen allergens as this sensitivity produces not only season but perennial clinical symptoms in nearly 50% of patients. The author discusses also botanical relations and cross reactions in allergy to mugwort and ragweed pollen allergens. PMID- 2098734 TI - [Desensitization at the first stage of IGE-mediated response as hay fever prophylaxis]. AB - The aim of our work was to assess the prophylactic aspects of desensitization at the first stage of IgE-mediated response to grass pollen antigens (GPA). Forty six patients aged 10-45 (Me = 20.45) years (group I) and 50 patients aged 11-45 (Me = 19.17) years (group II) were included in to the study. All of them: 1) suffered from allergic rhinitis due to house dust (HD), feathers (F), weed (W) or tree (T) pollen, 2) had also some other allergic diseases, 3) had positive family history of allergic disorders, 4) had reproducible, strongly positive skin reaction of type I to GPA, but 5) did not show any clinical symptoms of hypersensitivity to GPA. Specific immunotherapy with HD, F, W, and T aqueous extracts was administered to both groups for at least 3 successive years, while parallel desensitization with GPA aqueous extract was carried out in group I, only. The symptoms of grass pollinosis were searcher for and the effects of immunotherapy were evaluated in all the patients over the period of at least 5 successive years after the complete course of vaccines administration. Clinical signs of hypersensitivity to GPA became evident in 6 patients (13.04%) of group I and in 27 patients (54.00%) of group II (p less than 0.001). Thus the desensitization at the first stage of IgE-mediated response to GPA effectively prevented development of the symptomatic hay fever. However, the disease revealed itself in few cases still much later and its course was much milder than in people who were not subjected to such a preventive desensitization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098735 TI - [A preliminary assessment of the incidence of atopy at a workplace in Cracow]. AB - Skin tests, IgE level and eosinophils percentage were determined in 337 employees of the "Hydrokop" Works in Cracow. These investigations aimed at seeking more specific markers of allergy than anamnesis and skin tests. Allergy was reported by 108 individuals (38%). Some features of atopy were confirmed in 7.5%. Skin tests were positive in 36 individuals and were related to atopy in 55%. IgE levels were 10 IU/ml--greater than 1000 IU/ml with the distribution similar to log-normal. Mean IgE concentration was relatively high (202 IU/ml, in the individuals with confirmed congenital allergy. Percentage of eosinophils exceeded 3% in 39 subjects out of which 17 reported the symptoms of allergy. IgE level and percentage of eosinophils are controversial as the markers of atopy due to the contribution of various non-allergic factors while skin tests correlate well with allergic diseases which were relatively frequent in the examined group. PMID- 2098736 TI - [Family history of allergy and symptoms of atopic dermatitis]. AB - Three hundred sixty five children and hundred thirty nine adults with atopic dermatitis were divided into three groups. Group A included patients with negative family history of allergy; group B--allergy history in one parent or his family; group C--allergy in both parents or their families. It was found that total IgE level was higher in patients of group C in comparison with group A. Similarly, bronchial asthma and/or rhinitis coexisted more frequently, incidence of urticaria was higher and its onset earlier in patients of group C. The results noted in patients of group B occupied middle position between those in group A and group C. Results related to the incidence of RAST positive reactions and multiple sensitivity were similar but the differences were lower. Radioimmunologic assays were performed only in part of the tested patients. PMID- 2098738 TI - [Hematologic masking of sarcoidosis]. PMID- 2098737 TI - [Sensitivity to the primary house dust allergen--dermatophagoides pteronyssinus- in patients with atopic dermatitis]. AB - The study involved 117 adults and 535 children with atopic dermatitis. Immunoglobulins E against D. pteronyssinus--main allergen of the home dust--were assayed with RAST technique in children and FAST technique in adult patients. It was found that the blood serum IgE levels increase with patients' age and is the highest in patients with coexisting allergic respiratory diseases (difference statistically significant). RAST precision was compared with that of "prick" skin tests in the detection of allergy to home dust mites. Desensitization of 15 patients with home mite allergen produced satisfactory effects. PMID- 2098739 TI - [PAF--platelet activating factor, its significance in pathophysiologic processes]. PMID- 2098740 TI - [Progress in the treatment of chronic myelocytic leukemia]. PMID- 2098741 TI - [Prognostic usefulness of certain defined indicators for achieving complete remission and survival of ANLL in adults: proposal of a prognostic scale]. AB - Retrospective analysis has included 323 patients with acute nonlymphocytic leukaemia. The comparable patient groups were treated since 1981, according to protocols used by the Polish Acute Leukaemia Group. The prognostic value for achieving complete remission and survival of 67 pre-treatment factors (42 quantitative and 25 qualitative) was evaluated. The most important 9 parameters were scored according to their prognostic value as follows: age, percent of blasts in bone marrow, peripheral blood blast count, morphological subtype, percent of granulocytes in bone marrow, percent of blasts with CD-15 antigen, thrombocyte count, spleen/liver enlargement, CSF protein levels. Proposed scoring system enables classification of ANLL patients to a standard and high risk groups. PMID- 2098742 TI - [Results of treatment of Hodgkin's disease in children. Observation of 203 cases treated with modified MVPP regimen combined with local radiotherapy]. AB - Totally 209 children were treated within 1971-1982. Complete remission was achieved in 95.6%. Recurrence was noted in 36 patients (18.6%); 20 patients (9.9%) died due to progression of the disease and 9 patients (4.4%) because of complications. The first remission remains constantly in 150 patients for 63-206 months, including that after completion of therapy during 45-206 months. Asymptomatic 5- and 10-year survivals are the following: 82.9% and 80.1% respectively; 5- and 10-year survivals 91.9% and 89.8%, respectively. Expanded experience served as base to design a new regimen (introduced in 1988) which is being supposed to reduce untoward reaction by decreasing the number of MVPP cycles and irradiation doses. PMID- 2098743 TI - [Effect of livex on hypochromic anemia]. AB - Livex is a lyophilised preparation of the bovine blood which contains 70% of proteins and 0.3% of iron. Livex was given to 25 patients with iron deficiency anemia (group I), and 25 patients with lymphoreticular malignancies accompanied by iron deficiency with or without anemia. The dose was 5 g t.i.d. for 3 months. The majority of patients of group I were women. Excessive menstrual bleeding and chronic gastritis were most common causes of iron deficiency in this group. Livex statistically significantly increased hemoglobin, hematocrit, corrected reticulocyte count, mean erythrocyte hemoglobin, serum iron, percent transferrin saturation, and leukocyte count. Therapy produced significant increase in serum iron, total iron binding capacity, and percent transferrin saturation in patients with lymphoreticular malignancies. PMID- 2098744 TI - [Thymoma and thymoma-like tumors of the anterior mediastinum--therapeutic problems in observed patients]. AB - In the last years, 11 patients with tumors of anterior mediastinum were treated at the Oncologic Centre in Lodz. Lymphocytic-epithelial thymoma was diagnosed in 6 patients whereas thymoma was suspected in 5 patients. Therapy was a problem mainly in these 5 patients, especially if lymphoma was considered in the differential diagnosis. The authors suggest that therapy should start with cytostatic agents in all patients with mediastinal tumors and morphology which not justifies thymoma diagnosis. Radiotherapy may follow in these cases in which 1-2 chemotherapy cycles failed. PMID- 2098745 TI - [Changes in serum proteins in patients with allogenic bone marrow transplantation]. PMID- 2098746 TI - [Acute ischemia and heart failure during cyclic chemotherapy in a patient with plasmocytic myeloma]. PMID- 2098747 TI - [Myeloblastoma of the brain and spinal cord in a patient with acute myelomonocytic leukemia]. AB - A case of the myeloblastoma involving brain and spinal cord in a patient with acute myelomonocytic leukemia is reported. Numerous mitoses within the tumor provide an evidence for local cell proliferation in the neoplasm. Surgery combined with radiotherapy is suggested as the most efficient modality of the treatment. PMID- 2098748 TI - [Biology and clinical course of idiopathic thrombocytopenia (primary)]. PMID- 2098749 TI - [Carnitine in human physiology and pathology]. PMID- 2098750 TI - The long-term clonidine treatment induced behavioral depression in rats. AB - Effects of acute and long term clonidine treatment on motor and exploratory activities in rats were investigated in the presence and absence of imipramine. Rats received saline (control), clonidine HCl (0.8 mg/kg), imipramine HCl (30 mg/kg) and clonidine in combination with imipramine for 15 days. Clonidine caused hypoactivity and loss of interest and investment in the environment both acutely (on day 1) and chronically (on day 15). These effects of clonidine were reversed by acute and chronic imipramine pretreatments. Chronic clonidine treatment seemed more suitable in producing a model for depression in rats. PMID- 2098751 TI - Studies on the participation of the dopaminergic system in the central effects of chelidonine. AB - Chelidonine administered to rats in doses of 25, 50, 100 and 200 mg/kg ip exerted an inhibitory effect on the dopaminergic structures in the rat. It was shown that chelidonine decreased amphetamine- and apomorphine-induced hyperactivity and inhibited amphetamine and apomorphine sterotype. Besides, chelidonine significantly inhibited the yawning and penile erection produced by apomorphine. However, chelidonine potentiated also catalepsy caused by haloperidol. In doses of 100 and 200 mg/kg ip chelidonine depressed the whole brain dopamine (DA) concentrations and enhanced DA utilization. PMID- 2098752 TI - Some central effects of opipramol given repeatedly. AB - Some central effects of opipramol administered repeatedly (twice daily, 14 days) were studied in rats and mice. Repeated or acute treatment with opipramol did not change the locomotor activity of rats. Given repeatedly, but not in a single dose, opipramol increased the (+)-amphetamine-induced hyperactivity. The (+) amphetamine-induced stereotypy was unchanged by acute or repeated treatment with opipramol. The aggressiveness induced by clonidine in mice was attenuated by a single dose of opipramol, but it was markedly enhanced after repeated treatment with this drug. The immobility time of rats (behavioral despair test) was prolonged by a single dose of opipramol; when given three times, opipramol reduced the immobility time. The obtained results seem to indicate that repeated treatment with opipramol leads to similar effects in the experimental models as those after repeated treatment with typical antidepressant drugs, i.e. enhancement of the responses mediated by dopamine receptors (probably in the limbic system, but not in the striatum) and alpha 1-adrenoceptors in the brain. PMID- 2098754 TI - Lack of genotoxic activity of metronidazole and P1 derivative in two eukaryotic tests. AB - Metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole] and P1 derivative [1 (2-hydroxy-3-methoxypropyl)-2-methyl-4-nitroimidazole] were investigated for their genotoxic activity in two eukaryotic tests: mitotic recombination in yeast and micronucleus test in mice. Both compounds showed no genotoxicity in these eukaryotic assays contrary to their well-documented mutagenic activity in microbial short-term tests. PMID- 2098753 TI - Contribution of prostanoids to gastric circulatory and metabolic actions of solcoseryl. AB - Solcoseryl, a deproteinized extract of calf blood has been used in the treatment of peptic ulcer, but the mechanisms responsible for its therapeutic properties remain elusive. The present study was designed to determine the effects of solcoseryl on gastric total (GBF) and mucosal (MBF) blood flow, gastric oxygen consumption (GVO2) and mucosal formation of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) in anesthetized dogs. Soloseryl given iv or ia into the oxyntic gland area of canine stomach caused a dose-dependent increase in the GBF, MBF and GVO2, PGE2 and LTC4 contents in the ethanol-treated gastric mucosa showed a 5-12 fold increase over the values in the intact mucosa. The generation of LTC4, but not PGE2, was significantly diminished by solcoseryl. Pre-treatment with indomethacin completely prevented the effects of solcoseryl on mucosal PGE2, but not LTC4 levels, and significantly reduced its circulatory and metabolic actions on the stomach. The results of these studies indicate that solcoseryl causes dilatation of gastric arterioles and precapillary sphincters thereby improving mucosal blood flow and oxygen supply. The results also suggest that endogenous prostaglandins serve as mediators of the vascular and possibly metabolic effects of the drug on the stomach. The observed reduction by solcoseryl in gastric biosynthesis of LTC4 during mucosal injury may be an important factor in the gastroprotective and anti-ulcer effects of solcoseryl. PMID- 2098755 TI - Synthesis of two new angiotensin II analogs. AB - The synthesis of two new angiotensin II analogs: [Des-Arg2, epsilon Ahx1] angiotensin (II (1) and [Des-His0)-angiotensin (II (2) is reported. Rather strong agonist activity shows analog (1)-78% and weak-analog (2)-30% of the contractile activity of angiotensinamide. None of the synthesized peptides has antagonist activity. PMID- 2098756 TI - Synthesis and preliminary pharmacological assessment of novel gamma hydroxybutyric acid derivatives. AB - Synthesis and properties of new N-substituted amides of alpha-(1,1-ethylenedioxy) ethyl-gamma-hydroxybutyric acid are described. The compounds were obtained by aminolysis of 3-(1,1-ethylenedioxy)-ethyltetra-hydrofuran-2-on with primary alkylarylamines. Preliminary pharmacological assessment revealed that the compounds exert weaker influence on the central nervous system than the reference gamma-hydroxybutyric acid. Three of the novel compounds offered some protection against pentetrazole-induced tonic seizures in mice. PMID- 2098757 TI - [Bacterial contamination of the atmosphere in the dental surgery during preparation with turbine tools]. AB - The aerosol formed during work with turbine tools has an undesirable impact on the environment of dental surgeries. It may cause atmospheric transmission of infection. Recent qualitative and quantitative evaluation of aerosols assumes theoretical knowledge of physical and chemical properties and transformation of the aerosol system. These findings which influenced the selection of methods of the author's more recent measurements are the subject of the submitted paper. PMID- 2098758 TI - [Condition of the periodontium of medical students, Palacky University, Olomouc, by means of the CPITN Index]. AB - The authors examined 126 medical students of the Stomatological branch, Palacky University, Olomouc--Czech and Slovaks--and 32 foreign students from developing countries. The examination under standard conditions assessed the state of the periodontium and the need of periodontological treatment. Despite the fact that in dental students we must foresee a professional attitude and knowledge of the problem, the need of periodontological cases is increasing with the extent of professional training. 10% of the 5th year dental students require a surgical operation of the periodontium. The final conclusions will be made after evaluation of the whole longitudinal study. PMID- 2098759 TI - [Initial experience with ultrasonic diagnosis of impaired glued connections in dental prosthetics]. AB - The author evaluates the quality of gluing of metal discs by means of Spofacryl on glass, using ultrasound signals. He gives an account of his initial experience with this method which he considers so far suitable only for experimental work. PMID- 2098760 TI - [Injuries of the facial skeleton in children]. AB - An analysis of a group of patients hospitalized in 1985-1989 at the Dental Clinic for Children on account of facial injuries revealed a higher incidence of injuries in boys, as compared with girls, the ratio being approximately 1.8:1. The highest incidence was recorded in the group aged 9-10 years. Among skeletal injuries isolated mandibular fractures predominated followed by isolated fractures of the alveolar processes (19%) and isolated fractures of the middle portion of the face (12%). The most frequent fracture was that of the articular process of the mandible. 20% of the injuries patients had associated injuries, mostly of the CNS. In the aetiology of facial skeletal fractures falls from a bicycle held an important place (28%). From the therapeutics aspects 68% of the cases were treated by conservative methods, 25% were operated and 7% were left without treatment. PMID- 2098761 TI - [Hyperplasia of the coronoid processes of the mandible--case-history]. AB - Hyperplasia of the coronoid processes of the mandible in a 36-year-old man was associated, in addition to difficult opening of the mouth, with noises of apparently articular origin. The noise was due to the shifting of the coronoid processes along the inner surfaces of the temporal processes of the facial bones. On the X-ray picture also the elongated styloid processes were striking as well as symmetrial exostoses at the lower borderline of the mandible and condylar processes deformed without any apparent cause. PMID- 2098762 TI - [Analysis of the soft tissue profile--review]. AB - The author present a brief account of analyses of the soft tissue profile and their development. The review comprises in particular work which influenced the further development of profile analyses and contributed to the development of methods used at present. PMID- 2098763 TI - [Illumination apparatus--"cold light", designed by the authors, in stomatochirurgical practice]. AB - The authors describe an illumination apparatus--"cold light" of their design which meets the demands of the most pretentious intensity of illumination in stomatochirurgical practice. They recommend the apparatus also for other medical disciplines. PMID- 2098764 TI - Studies on medicamentous inhibitory therapy for esophageal precancerous lesions- 3- and 5-year inhibitory effects of antitumor-B, retinamide and riboflavin. AB - Since 1983, we have been conducting inhibitory therapy for precancerous lesions of the esophagus in two regions of Henan Province considered high-risk areas of esophageal carcinoma. Our goal was to effect a 50% reduction in the canceration rate of marked esophageal dysplasia. By means of a cytological survey, 2531 cases of marked esophageal dysplasia and 3393 cases of mild esophageal dysplasia were selected. The former were randomly divided into 3 groups for antitumor-B (ATB, a mixture of Chinese herbs), retinamide (4-ethoxycarbophenylretinamide) and placebo treatment respectively, and the latter into 2 groups treated with riboflavin and placebo respectively. Treatment was continued for 3 or 5 years (administration rate greater than 90% in all groups) and esophageal cytology reexamined (reexamination rates were 94.1% and 92.5% respectively). Our results were as follows: 1) ATB 3- and 5-year subjects saw the canceration rate of marked esophageal dysplasia drop by 52.2% and 47.3% respectively as compared to control (P less than 0.01). 2) Retinamide lowered the canceration rate by 37.3% after a 3 year treatment period, with this reduction reaching 43.2% after an additional 2 years of treatment with increased dosages (P less than 0.05, P less than 0.01). 3) In the riboflavin group, the canceration rate of mild esophageal dysplasia was reduced by 22.2% and 34.8% after 3 and 5 years of treatment respectively, but these differences were not statistically significant. The above results verify the efficacy of medicamentous inhibitory therapy for esophageal precancerous lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2098765 TI - Cytogenetic analysis in patients with myelodysplastic syndrome. AB - Forty-six patients with myelodysplastic syndrome (MDS) were studied. Chromosomal abnormalities were observed in 20 of the 46 patients (43%). Abnormalities of chromosome No. 5 occurred in 6 patients (13%); four of them had a deletion of the long arm of this chromosome [del (5q)]. Four patients had monosomy 7 (8.6%), and six patients had trisomy 8 (13%). Our results suggest that chromosomal abnormalities, deletion (5q), monosomy 7 and trisomy 8, might play important roles in the pathogenesis of MDS. PMID- 2098766 TI - In vitro influence of enkephalins on the proliferative response of mouse and rat splenic lymphocytes to phytohemagglutinin. AB - The opioid peptides leucine enkephalin (LENK) and methionine enkephalin (MENK) were investigated for their effect on the proliferative response of activated BALB/C mouse and Sprague-Dawley rat splenic lymphocytes in vitro. The results showed that LENK and MENK (1 x 10(-3) mg/ml to 1 x 10(-13) mg/ml) significantly suppressed the proliferative response of mouse lymphocytes to phytohemagglutinin (PHA) and enhanced the proliferation of rat lymphocytes at peptide concentrations similar to those effective in mice. It is proposed that endogenous ENKs play a neuroendocrine role between the central nervous system and the immune system. PMID- 2098767 TI - Studies on antipeptic ulcer agents: a structure-activity relationship analysis of aldehyde semicarbazones and aryl hydrazones. AB - Twenty-eight condensation products of heterocyclic-a-carboaldehydes with N aminooxazolidones, semicarbazides, thiosemicarbazides and benzoxycarbonyl hydrazide were synthesized so as to deduce the antiulcer pharmacophore or fragment of furazolidone (I), a prototype which has shown therapeutic efficacy in patients with gastric and duodenal ulcers. SAR analysis of the compounds indicated that the substitution of furan, thiophene, pyrrole or N-methyl pyrrole rings for 5-nitrofuran and the cleavage of the oxazolidone ring did not fully destroy the activity. The electron density of the carbonyl group was found to be of importance. A lead structure, therefore, was derived for further optimization. PMID- 2098768 TI - Effects of parathyroid hormone and calcitonin on calcium transport of rat cultured striatum cells. AB - The effects of human parathyroid hormone (hPTH 1-34) and calcitonin on Ca2+ transport in resting and KCl-depolarized cultured cells of rat striatum were studied. The results showed that in resting cells PTH significantly increased both Ca2+ uptake and efflux, while calcitonin had no effect on either. In KCl depolarized cells the Ca2+ uptake was increased by PTH and reduced by calcitonin, and the effluxes were reduced by both PTH and calcitonin. These results suggest that the two hormones may alter the functions of neurons by regulating cytoplasmic Ca2+ levels. PMID- 2098769 TI - Cyclosporine A prolonged survival time of parathyroid gland allograft in rats. AB - We divided the experimental animals into three groups. In the first group, only cyclosporine solvent containing no cyclosporine was given to rats. In the second group, cyclosporine A was given intraperitoneally from the 1st to the 5th days after transplantation at a daily dosage of 2 mg/100 g BW. In the third group, besides the first courses of cyclosporine A treatment as in group II, second and third courses were given on the 30th to 34th and 60th to 64th days after transplantation. Our results show that a relatively large dose given in a short course together with intermittent enhancement treatment proves much more effective than a short course without enhancement treatment. PMID- 2098770 TI - Primary lymphoma of the lung. AB - Two cases of primary lymphoma of the lung are reported, both of which were misdiagnosed preoperatively as bronchogenic carcinoma before undergoing successful resection. Accurate diagnosis was obtained after operation. These two patients were in good condition after a short period of follow-up. A discussion is presented concerning diagnosis, treatment and prognosis. Also, we point out the reason why so few primary lymphomas of the lung are reported: the mass of the lymphoma is typically so large that surgeons may consider it to be lung cancer in a late stage and thus abandon surgical intervention, or it may be erroneously diagnosed pathologically as undifferentiated small cell carcinoma of the lung. PMID- 2098771 TI - The development of a high anti-interference heart sound sensor (type HYS-87). PMID- 2098772 TI - Ciganek's rhythm--prolonged observations with report of a case. PMID- 2098773 TI - Quality of life in patients with inflammatory bowel disease. AB - The term 'quality of life' is defined as the result of objective circumstances of life and subjective perceptions of patients. Health-related quality of life is a dynamic concept which changes during an adaptational process interacting with illness condition during the course of chronic inflammatory bowel disease. In a review on the research in this field, it is shown that quality-of-life assessment may be an important adjunct to the evaluation and treatment of patients with inflammatory bowel disease. The comparative evaluation of quality of life in patients treated medically and surgically may offer important information for decision making. PMID- 2098774 TI - A psychological support concept and quality of life research in a liver transplantation program: an interdisciplinary multicenter study. AB - Considering the increasing number of liver transplantations with longer periods of transplant function, there is a growing need for quality of life research in the field. In addition to lethality, mortality and rehabilitation, parameters of 'quality of life' are to be evaluated: the patient's rating of his subjective physical symptoms, psychological condition (anxiety, depression and mental adjustment), social reintegration and life satisfaction. This paper describes our psychological support program that has been established at the Hamburg LTX center as well as the first results of the ongoing QoL research study. Using the methods developed by the Hamburg Study group on 'quality of life in surgery', 38 liver transplantation patients of the University of Chicago (cross-sectional study with control groups of patients with chronic liver disease as well as healthy individuals) and 29 patients of the University Clinic of Hamburg (longitudinal study with points of evaluation before and 2, 6, 12, 24 and 36 months after transplantation) have been evaluated. First results: (1) All successfully transplanted patients show a significant postoperative increase of their overall quality of life. (2) The psychological parameters of quality of life are only partly correlated with physical symptoms. (3) There is a high correlation between rejection crisis periods and the decrease of all quality of life parameters. (4) In both samples men have a lower quality of life than women, (5) Preoperative depression and lack of social support might be considered as being possible risk factors for long-term survival. (6) Long-term survivors rate their quality of life significantly higher than patients with chronic liver disease and--despite some persisting somatic restrictions--as high as healthy controls. (7) A psychotherapeutic support program increases the patient's compliance resulting a better adaption to the transplant procedure including rehabilitation. PMID- 2098775 TI - Quality of life in adults with insulin-dependent diabetes mellitus. AB - Conventional measures of psychiatric or medical morbidity do not adequately reflect the consequences of chronic illness. Quality of life refers to a more comprehensive assessment of the impact of illness. Uncomplicated insulin dependent diabetes is usually associated with mild reported reduction in quality of life. Increased depressive and anxiety disorders have been reported in individuals with insulin-dependent diabetes mellitus, particularly in association with more severe medical complications and low social support. The potential benefits of intensive treatment approaches must be weighed against adverse effects on the quality of life. PMID- 2098776 TI - Psychological distress and quality of life in endocrine disease. AB - Despite an upsurge of research in psychoneuroendocrinology, there has been very little interest in the psychological aspects of clinical care in endocrine disease. The clinical and research implications of quality of life in endocrinology (life events preceding disease onset, psychological distress associated with acute illness and convalescence, abnormal illness behavior) are discussed. PMID- 2098777 TI - Quality of life in oncology patients. PMID- 2098778 TI - Quality of life in patients with end-stage renal disease in relation to the method of treatment. PMID- 2098780 TI - Quality of life in the medically ill: a psychosomatic approach. PMID- 2098779 TI - On a nonparametric combination method for dependent permutation tests with applications. AB - This paper deals with a combination method for dependent permutation tests, which is nonparametric with respect to the underlying unknown dependence structure. The method is based on a simulation or resampling procedure, conditional on the data, which provides a simulated estimate of the permutation distribution of any statistic. Applications to some unusual and quite complex testing problems are shown. PMID- 2098781 TI - On looking inward and being scientific. A tribute to Arthur H. Schmale, MD. AB - Paradoxically, Schmale's greatest contribution remains hardly known even to his admirers. That has been his challenge to the tradition disallowing introspection and dialogue as scientific instrumentalities. There can be no more appropriate tribute to Schmale at 65 than to call attention to how he has gone about refining everyday observation, introspection, and dialogue for scientific use. In so doing he reestablishes the ancient triad introspection-observation-dialogue as the basic scientific method of clinical study. PMID- 2098782 TI - Methodological and conceptual issues in research on quality of life. AB - Research on quality of life may herald a welcome psychosomatic change in biomedical research and clinical practice. The many promising horizons available, however, do not prevent miscommunication, random effort and faulty reasoning. An illusion of simplicity has caused many investigators to believe that the measurement of quality of life is simple and feasible, whereas only the psychosocial variables affecting quality of life can be assessed by current, reliable psychometric methods. The areas concerned with biomedical research on quality of life are reviewed and some methodological issues are discussed. PMID- 2098783 TI - Measurement of psychological distress and well-being. AB - Psychological distress and well-being are important aspects of quality of life measurements in psychosomatic medicine. The concept of improvement in medicine refers to a clinical distance along which the current state of the patient is compared to the pretreatment position. Quality of life covers, however, more than one distance or dimension in this respect; e.g. well-being, side effects of treatment, and psychosocial stressors. The psychometric aspects of these dimensions are analysed with reference to nomothetic and idiographic methods. The nomothetic approach is the selection of the most unbiased scale tailored to the disorder under investigation. The idiographic approach is the construction of a hermeneutical or meaningful scale for the individual patient. For both methods the clinical improvement index is the most appropriate statistic. PMID- 2098784 TI - Measuring the social dimension of subjective health in chronic illness. AB - This contribution discusses the social dimension of treatment-related subjective health in chronically ill patients. In its first part, it introduces two basic concepts, 'social performance' and 'social well-being'. These terms are further specified and discussed in the broader context of the notions of 'social support' and 'social adjustment'. The second part gives a selective, critical overview of currently used methods in the field. It is concluded that the existing gap between theory and measurement needs to be closed before substantial advancements in a comprehensive assessment of subjective health can be expected. PMID- 2098785 TI - Quality of life in cardiovascular disease. AB - Psychosomatic understanding of the consequences of cardiovascular disorders has had relatively little influence on the separate literature describing quality of life and evaluating interventions. This is partly because psychosomatic research has been too narrowly focussed but mainly because concepts and measures of quality of life take a limited view of its psychological aspects and neglect the significance of individual meaning. There is a need for more research which is based on carefully selected specific measures of quality of life chosen as being of particular importance to patients and to the hypotheses being tested. It is also essential to be aware of the wide range of individual response to cardiovascular disorders. Review of syndromes shows that there is considerable scope to improve understanding of the psychological aspects of quality of life and to develop and evaluate psychological interventions. PMID- 2098786 TI - [Dental assistant in Great Britain]. PMID- 2098787 TI - [Model course in oral hygiene instruction]. PMID- 2098788 TI - [Dental office as an art gallery]. PMID- 2098789 TI - [Cooperation between dental assistant and dental trade]. PMID- 2098791 TI - ["With growth" nipple size--important aid to jaw development]. PMID- 2098790 TI - [Saliva and caries prevention]. PMID- 2098792 TI - [Is marketing compatible with dental ethics? What the dental assistant should know]. PMID- 2098793 TI - [Comparative material science. 4. Material and aids in prosthetics (1)]. PMID- 2098794 TI - [How do I become a dental assistant?]. PMID- 2098795 TI - [Life-long healthy teeth--animal teeth]. PMID- 2098796 TI - [Group dental prevention in kindergarten]. PMID- 2098797 TI - [Comparative material science. 4. Materials and aids in prosthetics (2)]. PMID- 2098798 TI - [Dental nurse. Education, work and use in public health in East Germany]. PMID- 2098799 TI - [Success, What is it? Four years of prevention in a Hamburg kindergarten (2)]. PMID- 2098800 TI - [Contact psychology in dental practice (7)]. PMID- 2098801 TI - [Environmental concern--possibilities and limits in dental practice]. PMID- 2098802 TI - [History of eyeglasses. From "spectacled snake" thru modish accessory to "occupational dress"]. PMID- 2098803 TI - [Producing an esthetic complete denture (2)]. PMID- 2098804 TI - [Producing a combination denture. 3. Successful esthetics as a result of a reasoned concept]. PMID- 2098805 TI - [Preparation measures for consideration with combination dentures]. PMID- 2098806 TI - [Application of thermoplastic acetate resins in crown and bridge technique (2)]. PMID- 2098807 TI - [Renaissance of full porcelain? (1)]. PMID- 2098808 TI - [Contribution to manipulation of Bionators. 2. Laboratory preparation of Balters Bionator framework]. PMID- 2098810 TI - [Advantages and disadvantages of light-curing impression materials]. PMID- 2098809 TI - [Silicone duplication under pressure]. PMID- 2098811 TI - [Forming of the palatal seal of a complete denture]. PMID- 2098812 TI - [Swinglock--guidance in preparation]. PMID- 2098813 TI - [Gap care with inlay bridges]. PMID- 2098814 TI - [Renaissance in full porcelain (2)]. PMID- 2098815 TI - [Preparation of the diagnostic set-up]. PMID- 2098816 TI - [Clasp blending using Rocatec/Visio-Gem]. PMID- 2098817 TI - [Cerec System: ways and basics for cooperation between dentist and dental technician (1)]. PMID- 2098819 TI - [Dental casting with aid of HSL-laminate]. PMID- 2098818 TI - [Step child seeks foster parents]. PMID- 2098820 TI - [Ceramic blending with titanium--a work like every other one?]. PMID- 2098821 TI - [Simple and quick work with labial arch forceps]. PMID- 2098822 TI - [Structure and microstructure of dental porcelain in relation to firing condition]. PMID- 2098823 TI - [Cerec system: ways and basics for cooperation between dentist and dental technician (2)]. PMID- 2098824 TI - [Basic concepts of esthetic complete dentures (2)]. PMID- 2098825 TI - [Production of combination partial dentures. 1. Conceptual evolution]. PMID- 2098826 TI - [Limitations of manual crown margin formation (2)]. PMID- 2098827 TI - [Covering of discolored tooth stumps or metallic buildup with Optec System]. PMID- 2098828 TI - [Bavarian solution]. PMID- 2098829 TI - [Casting technique for gold alloys (1)]. PMID- 2098831 TI - [Alternatives to casting technique]. PMID- 2098832 TI - [Producing an esthetic complete denture (1)]. PMID- 2098830 TI - [Computer supported communication procedures with IMAGE software]. PMID- 2098833 TI - [Producing combination partial dentures. 2. Union of function and esthetics]. PMID- 2098834 TI - [Esthetic and functional aspects of precision dentures]. PMID- 2098835 TI - [Application of thermoplastic acetate resins in crown and bridge technic (1)]. PMID- 2098836 TI - [Natural appearance and harmony in accord with environment]. PMID- 2098837 TI - [Contribution to manipulation of Bionators. 1. Considerations of functionally relevant construction of Balters Bionator in Class II dysgnathia]. PMID- 2098838 TI - [Casting technique for gold alloys (2)]. PMID- 2098839 TI - [Importance of Albert Schweitzer and Albert Schweitzer Societies for humanitarian medicine and human rights]. PMID- 2098840 TI - [Human recombinant erythropoietin in the treatment of anemia in patients on long term hemodialysis]. AB - Recombinant human erythropoietin (EPO) was administered i.v. to anaemic patients (pts) on hemodialysis in doses from 40 to 120/IU/kg 3 times a week. 20 out of 21 pts showed an increase in hemoglobin (Hb) level above 11 g/dl after 8-12 weeks. Maintenance doses to keep Hb value about 10 g/dl varied from 2 X 40 IU/kg to 3 X 40 IU/kg per week (subcutaneous). EPO improved the well-being and physical condition in all of pts. Six pts developed rise in blood pressure and most an increase in predialysis serum potassium and urea levels during first 16 weeks of treatment. PMID- 2098842 TI - [Cholesterol and phospholipid levels in erythrocyte membrane of patients with blood lipid disorders and hypertension]. AB - The aim of this paper was search for possible relationship between cholesterol and phospholipids in erythrocyte++ membrane and pathological entities i.e. hypertension and dyslipidemia. Both are the main risk factors of atherosclerosis and in both condition disturbances at the cell membrane level were detected. 124 persons (both men and women in a age group 20-59), employees of industrial enterprise were included into study. Standard questionnaire was performed as well as body weight and height, blood pressure, biochemical tests-lipids, cell membrane lipids serum and intracellular electrocytes as well as 24 h electrolyte urine excretion. The following findings were reported: cell membrane cholesterol concentration correlates with sex, age, body weight, systolic and diastolic blood pressure and triglycerydes HDL-cholesterol and serum phospholipids. The biggest influence on cholesterol concentration in cell membrane have the following factors: sex, age and serum triglycerides. The most important finding was that the lipid metabolism disturbances has impact on triglyceride elevation in serum and that arterial hypertension is connected with decreased cholesterol concentration in erytrocyte membrane. PMID- 2098841 TI - [Effect of calcitonin on gastric emptying and postprandial secretion of gastrin and insulin in patients with duodenal ulcer]. AB - The effect of calcitonin on gastric emptying of a radiolabelled test meal was examined in 10 patients with an endoscopically confirmed duodenal bulb ulcer. According to a double-blind study protocol, the patients were given on two different days placebo or synthetic salmon calcitonin (415 pmol i.v. bolus followed by a 90-min infusion to reach an overall dose of 62.25 pmol.kg-1 body mass)--in randomized order. Calcitonin did not affect the postprandial gastrin release nor did it change significantly the serum calcium or phosphorus concentration. The abolished postprandial insulin release by calcitonin was accompanied by a different pattern of serum glucose concentration, when compared to the situation with placebo. In all patients examined calcitonin evoked a profound delay in gastric emptying--the mean gastric transit time, MTT90: 34.1 +/ 1.4 min (placebo) vs 41.0 +/- 1.1 min (calcitonin), p less than 0.001. PMID- 2098843 TI - ["Silicon--metabolic aspects of its effect on human body"]. PMID- 2098844 TI - [Hormonal regulation of lipoprotein lipase activity]. PMID- 2098845 TI - [Psychosocial risk factors of ischemic heart disease]. PMID- 2098846 TI - [The cardiovascular system in functional disorders of the thyroid gland]. PMID- 2098847 TI - [Diabetic cardiomyopathy]. PMID- 2098848 TI - [Oral contraceptives and diseases of the circulatory system]. PMID- 2098849 TI - [Obesity and the cardiovascular system]. PMID- 2098850 TI - [Organotherapy of Dioscorides]. PMID- 2098851 TI - [Albert Schweitzer, his principle "reverence for life" and present-day ecology]. PMID- 2098852 TI - [Morphologic study of the embryonic development of the Amazonian turtle Podocnemis expansa, Pelomedusidae]. AB - Two egg groups from four clutches of the Amazon turtle, Podocnemis expansa, were incubated at 32-34 degrees C and 35-38 degrees C, respectively. The incubation of the first group lasted approximately 47 days and the second 43 days. To standardize the stages, a series of 25 stages was recorded, based on observation of morphological evolution related to incubation duration and its respective temperatures. PMID- 2098853 TI - Alternative methods for the feeding of triatomines under laboratory conditions. AB - In order to improve the rearing and maintenance of triatomines under laboratory conditions, two feeding systems were made, one with a natural source in which a pigeon kept alive after several blood meals in triatomines was used and another artificial system using defibrinated sheep blood. Besides these equipments being made of easily available materials and low cost, they have shown to be useful and efficient, with favourable conditions for the feeding of triatomines. PMID- 2098855 TI - [Safety norms in anesthetic practice: fashion or necessity?]. PMID- 2098854 TI - Interaction of concanavalin A with sugar residues of collagen from different tissues. AB - Topochemical characteristics of reactions of different types of collagen containing structures with Concanavalin A (Con A) have not been considered up to now. In this study the presence and availability of glucose residues of collagen molecules from intestine, liver, cartilage and tendon are detected using Con A and horseradish peroxidase (HRP). In intestine, cartilage and tendon sections, the Con A-HRP method was only significantly positive when the sections were first submitted to treatment with papain. This suggested the presence of glycoproteins and proteoglycans of the extracellular matrix (ECM), which might interfere either interacting with lateral sugar residues of the collagen molecules, or causing some steric blockade or even masking as occurs in regions with a high state of compactness. PMID- 2098856 TI - [Analgesic and anticonvulsive effect of midazolam via intrathecal administration in the rat]. AB - We have studied analgesic and anticonvulsive effect of midazolam by means of tail flick test and electroshock respectively. The drug was administered via cervical and lumbar intrathecally in chronically implanted rats. Total doses were 50, 125, and 250 microg. Control animals received 0.3125, 0.625, 1.25 and 2.5 mg intraperitoneally. Degree of sedation was also measured with a motor activity scale with the purpose of correlating sedation with analgesic and anticonvulsive effect. Tail-flick test was carried out 5 and 30 minutes after the administration of midazolam. Results showed that lumbar intrathecal midazolam has analgesic effect in tail-flick test whereas cervical intrathecal or intraperitoneal midazolam has no analgesic effect and shows a non significant hyperalgesic trend. Cervical intrathecal and intraperitoneal midazolam has anticonvulsive effect. As sedative effect of the administered doses increases, there was also a not significant trend to shorten latency period of tail-flick test and to increase anticonvulsive effect. PMID- 2098857 TI - [Comparison of anesthesia with thiopental or etomidate in short duration operations]. AB - Forty ASA I-II women who were scheduled for uterine curettage were randomly allotted to two groups of 20 patients each. Both groups were age- and weight- matched. They were pre-treated with atropine (0.01 mg/kg) and diazepam (0.1 mg/kg). Anesthesia was induced with 2.5% thiopental (5 mg/kg) or 0.1% etomidate (0.3 mg/kg) and was maintained with N2/O2 at 50% and isoflurane at 1% adding supplementation doses of inducer (20% of initial dose) when required. Quality of induction and maintenance of anesthesia, cardiovascular effects, secondary effects and quality and rapidity of awakening were evaluated. Etomidate patients presented a higher number of secondary effects and pain on injection of the drug (p less than 0.05) and occurrence of excitatory motions (p less than 0.01) attained statistical significance. Evaluation of anesthesia quality was significantly higher with thiopental (p less than 0.05). There were no differences with respect to the remaining studied variables. We conclude that etomidate when used as unique agent in anesthesia induction has no advantages over thiopental in healthy patients undergoing short duration operations. PMID- 2098858 TI - [Pharmacokinetics of mepivacaine and lidocaine after epidural administration]. AB - We compare plasma concentrations of mepivacine (MPV) and lidocaine (LDC) after epidural injection in 20 patients. Samples were drawn at 1, 5, 10, 15, 20, 60, and 120 minutes after administration. Absorption from epidural space is equally fast for both anesthetic agents (t max 20 +/- 7 minutes for MPV and 25 +/- 12 minutes for LDC) resulting in high values of Cmax: 7.8 +/- 3.3 microg/ml for MPV and 2.6 +/- 0.7 microg/ml for LDC (p less than 0.001). Mean values of K and Vd were 0.0076 +/- 0.0020 minutes-1 for MPV versus 0.0087 +/- 0.0032 minutes-1 for LDC and 0.9 +/- 0.7 1/kg for MPV versus 1.8 +/- 0.6 1/kg for LDC (p less than 0.001). PMID- 2098859 TI - [Surveillance and monitoring criteria in anesthesiology, resuscitation and pain therapy. Recommendations of the Spanish Society of Anesthesiology and Recovery (SEDAR). Board of Directors of the Spanish Society of Anesthesiology, Recovery and Pain Therapy (SEDAR)]. PMID- 2098860 TI - [Antionio Morales Perez and thermal etherization]. AB - During the last decades of XIXth century, after a 40-year parenthesis, interest on ether as anesthetic agent is being elicited again in some European countries. In the present paper, we study the personal method of Antonio Morales, the Spanish surgeon. His method, the so-called thermic etherization, is encompassed within the group of techniques that were based on anesthetic vapor heating techniques. We also describe the device designed by Morales and the changes that were introduced later on. PMID- 2098861 TI - [Myasthenia gravis]. AB - The present review updates myasthenia gravis. Immunopathogenesis of this condition, the clinical picture and degrees of involvement according to Osserman's classification, diagnostic procedures currently available, medical treatment and repercussion on the patient who is going yo be thymectomized are discussed. We review the works of several authors as far as concern to the use of muscle relaxants in myasthenic patients, peroperative monitoring of neuromuscular blockade, anesthetic techniques to be used, analgesia and intensive care required during postoperative period. PMID- 2098862 TI - [Periorbital hematoma as a complication of posterior peribulbar anesthesia]. AB - We report a case of a large periorbital hematoma which furtherly extended to the ipsilateral orbit and appeared after posterior peribulbar blockade in a 70-year old woman undergoing cataract extraction and intraocular implant. Peribulbar blockade was carried out with a 23-gauge blunt bevel Atkinson's needle introduced at the level of nasal or internal angle of the upper lid without loosing contact with the ceiling of the orbit. Anesthetic solution was bupicavaine at 0.75% with 10 U/ml of hyaluronidase, 3 ml. Usual blockade of lower lid was not carried out as with the first blockade, an almost complete paresis of extraocular muscles together with discrete conjunctival ecchymosis occurred. Ocular compression was conducted with Homan's balloon at 30 mmHg gor 30 minutes. Then, the eyeball was decompressed and a progressive increase of edema with conjunctival hemorrhage becoming bilateral was observed. Coagulation tests were normal. The incidence of conjunctival ecchymosis and palpebral hematoma with such technique ranges from 2% to 9%; it does not represent any intraoperative problem but may difficult surgery. PMID- 2098863 TI - [Anesthesia in two patients with motor neuron disease]. AB - We report two cases of patients diagnosed of motoneuron disease. First patient had amyotrophic lateral sclerosis with bulbar involvement and developed prolonged apnea after general anesthesia for elective hemorrhoidectomy. Second patient had Kugelberg-Welander disease or type III hereditary mononeuron disease, underwent laparotomy and had no anesthetic complications. Patients with motoneuron disease should be considered as high anesthetic risk patients because they may develop respiratory complications accordingly to their previous muscle involvement so neurologic and respiratory assessment is basic. The use of succinylcholine should be limited to cases in whom external denervation and muscle atrophy may be ruled out. Short half-life muscle relaxants such as atracurium and vecuronium are advised with monitoring of neuromuscular function. Currently, local-regional techniques are not contraindicated. PMID- 2098864 TI - [Myasthenia gravis: thymectomy. Muscle relaxation with atracurium besilate]. AB - We have carried out a prospective study on the use of the muscle relaxant, atracurium besilate, in 10 patients with myasthenia gravis, seven had type IIB and three had type IIA, who were scheduled for thymectomy, using ED95 0.20 mg/kg, and ten non myasthenic patients undergoing cholecystectomy using ED95 0.50 mg/kg. After monitoring neuromuscular transmission, the time for establishing maximum blockade (EMB), clinical efficacy time (CET), recovery index (RI) and total duration time (TDT) were measured and evaluated comparatively. Results showed that in myasthenics patients, EMB was faster, CET an TDT were more prolonged and RI was higher than in non myasthenic patients. We conclude that atracurium at doses of 0.20 mg/kg is currently the non depolarizing muscle relaxant of choice in myasthenic patients because of the excellent muscle relaxation allowing extubation in the operating room without reverting muscle blockade and not needing ventilatory support during postoperative period. PMID- 2098865 TI - [Prophylaxis of acid aspiration]. PMID- 2098866 TI - [Epidural anesthesia in a high risk patient undergoing thoracotomy]. PMID- 2098867 TI - [Epidural analgesia versus conventional intravenous analgesia after aortic surgery]. PMID- 2098868 TI - [Historical evolution of scientific-medical publishing in anesthesiology]. PMID- 2098869 TI - [Local-regional anesthesia in Steinert's disease]. PMID- 2098870 TI - [Prolonged neuromuscular blockade due to interaction between pancuronium bromide and gentamicin]. PMID- 2098871 TI - [Anaphylaxis due to hydatidosis in the immediate postoperative period]. PMID- 2098872 TI - [Patient-controlled analgesia]. PMID- 2098873 TI - [Ineffectiveness of incentive spirometry as coadjuvant of conventional physiotherapy for the prevention of postoperative respiratory complications after thoracic and esophageal surgery]. AB - We have studied the efficacy of routine use of incentive spirometry (IS) in two groups of patients: group 1 (n = 18) with IS, and group 2 (n = 19), no IS. All patients suffered from lung or esophagus neoplasm and received respiratory physiotherapy before and after the operation. They underwent high chest and abdomen surgery. The incidence of alterations of pulmonary auscultation, roentgenologic abnormalities and alterations of the alveolar-arterial difference of oxygen (D[A-a]O2) as well as postoperative complications were similar in both groups. Patients undergoing digestive surgery presented a higher frequency of pleural effusion (p less than 0.05) and of them, the subgroup with IS stayed at the hospital for a longer time (47.2 +/- 32 days) than the subgroup undergoing digestive surgery not submitted to IS (p less than 0.01) probably because of the higher incidence of neoplasms of the mean third of the esophagus in such group. In our study and in the context of the type of surgery studied, the routine use of IS does not decrease the frequency of clinical and roentgenologic alterations neither improves the efficacy of postoperative gas interchange. PMID- 2098874 TI - [Diazepam reversion with flumazenil. Gasometric and sympathetic-adrenal study]. AB - We report the effects of flumazenil as reversion agent of the effects of diazepam at high doses as a part of short-duration general anesthesia. We have studied ten women in ASA I general condition who received anesthesia with fentanyl, 2.5 micrograms/kg-1, diazepam, 0.4 mg/kg-1 and O2/N2 at 60%. At the end of the operation, flumazenil, 0.2 mg, was administered. Hemodynamic, respiratory and adrenergic effects were evaluated. The degree of awareness and subjective feeling of the patient at awakening were also evaluated. After administration of flumazenil, awareness state was significantly higher (p less than 0.001) and it persisted during the duration of the study (120 minutes). Respiratory rate and pO2 increased significantly with administration of flumazenil (p less than 0.25 and p less than 0.01, respectively) and pCO2 decreased from 42.2 mmHg to 37.9 mmHg (p less than 0.05). Neither hemodynamic parameters nor plasma concentration of catecholamines changed significantly. As secondary effects attributable to flumazenil, four patients complained of nausea and one patient referred anxiety. We conclude that flumazenil allows to carry out anesthetic techniques with high doses of benzodiazepines even in short duration interventions with safety and without cardiocirculatory nor sympathetic-adrenal alterations. PMID- 2098876 TI - [Degrees of acceptance of local regional anesthetic techniques among hospital physicians]. AB - We have evaluated the acceptance of local regional anesthetic techniques (LRA) among the physicians of our hospital by means of an anonymous questionnaire. The people addressed had to choose, as if they were hypothetical patients, the type of anesthesia (general or local regional anesthesia) in four clinical hypothetical situations: interventions on upper limb (UL), on lower limb (LL), in an emergency situation and in a scheduled situation. We obtained 109 answers: 58 from medical specialities (cardiology, gastroenterology, internal medicine, pneumology, and radiology) and 51 from surgical specialities (general surgery, gynecology, ear, nose and throat, and traumatology). Local regional anesthetic techniques were the most frequently selected (p less than 0.001) and the main reason for selection was safety. Surgeons choose LRA more frequently than medical specialists but the difference was not significant. More information on such techniques does contribute to an increase in its acceptance, a fact which is clearly reflected in the medical staff of our hospital. PMID- 2098875 TI - [Comparative study of detection methods in epidural anesthesia: Episensor and loss of resistance]. AB - The aim of the present study is to evaluate an electronic detector of negative pressure (Episensor, Palex, Spain) designed for the identification of epidural space. Ninety patients were randomly assigned to two groups: group 1 (n = 47) received epidural anesthesia as perioperative analgesic technique with Episensor method and group 2 (n = 43) received epidural anesthesia with the classic method of loss of resistance with gas mandrin. The following parameters were studied: a) demographic features, b) characteristics of epidural anesthesia, and c) complications occurring during space detection. There were no statistical differences in the analysis of demographic variables neither in the quality of the epidural anesthesia achieved in both groups. With respect to complications, group I presented the highest number of complications although only the lack of detection of epidural space achieved statistical significance (8.5%, p less than 0.05); the incidence was lower than that reported in the literature as physiologically possible in the lumbar epidural segment. We conclude that progressive knowledge of Episensor may decrease the initial incidence of complications with a success rate similar to that of classic techniques of identification of epidural space. PMID- 2098877 TI - [Treatment of chronic pain of oncologic origin with epidural or intrathecal morphine administered by continuous or programmable flow implanted pumps]. AB - We have treated a total of 40 patients who presented chronic pain secondary to a neoplastic condition; the patients were treated with morphine in a continuous perfusion by means of an implanted perfusion pump. The route used was the epidural route in seven patients and the intrathecal route in the remaining 33 patients. In 22 patients, the implanted pump was the continuous flow Infusaid model and in the remaining 18, the programmable flow Synchromed (Medtronic) model. The daily dose of morphine ranged from 2.4 mg to 48 mg and maximum perfusion period was 19 months. Main complications were displacement of the catheter and rejection of perfusion system. Despite its high prize, we believe that such treatment system should be considered because of the quality of life improvement of the patients. PMID- 2098878 TI - [Succinylcholine apnea]. PMID- 2098879 TI - [Intra-arterial regional anesthesia]. AB - One of the most easy and effective ways for obtaining insensibility at the extremities, with a minimal danger for the patients, is the intravenous regional anesthesia. However, the origin of this type of anesthesia still remains controversial. Some of the questions suggested by this theme are answered in this article. It is very likely that the basis of this technique were established by Dr. Jose Goyanes Capdevila, who by the beginning of this century was a lecturer in Surgery at Madrid's University. It must be considered that he used the arterial pathway following the anatomical and physiological criteria in use then. PMID- 2098880 TI - [Traumatic tear of the diaphragm]. AB - We have carried out a 9-month retrospective study in the Emergency Resuscitation Unit; 21 patients with abdominal trauma, 42 patients with chest trauma and 895 patients with multiple injuries were treated; 197 (22%) of the latter had also chest and/or abdomen involvement. Of the 260 patients with chest and/or abdomen involvement, six (2.3%) patients had traumatic tear of the diaphragm and four of them, presented thoracic herniation of abdominal content. Diagnostic suspicion was entertained in five patients by means of x-ray plain chest film; diagnosis was confirmed by a barium meal in two patients. In one patient, the diagnosis was established perioperatively. All patients had associated lesions. Four patients required mechanical ventilation after the operation. One patient died of cardiogenic shock on the fourth postoperative day. We emphasize the importance of the suspicion of such condition in patients with multiple injuries with chest and/or abdomen involvement. PMID- 2098881 TI - [Stevens-Johnson syndrome associated with esophageal stenosis]. AB - Stevens-Johnson syndrome consists of inflammatory bullous lesions of the skin and mucous membranes and seems to be associated to several pharmacologic and/or infectious triggering factors which might share a common immunologic way. Esophageal stenosis secondary to Stevens-Johnson syndrome is very rare. During the last 40 years, only two cases in children have been reported. In the present work, we report clinical features and anesthetic management of a 6-year-old girl requiring seven general anesthesia procedures with ketamine and isoflurane for correction of esophageal stenosis. PMID- 2098882 TI - [Anesthesia of a woman with extreme morbid obesity (260 kg)]. AB - Patients with morbid obesity present a series of functional and morphologic alterations and require a careful planning for anesthetic management. We report a case of a woman weighing 260 kg who was operated on twice for the treatment of her base condition. In the first operation, general anesthesia was carried out and in the second one, epidural anesthesia was conducted. Main complications included hypoxemia and hypercapnia which persisted during the first week after operation carried out under general anesthesia. PMID- 2098883 TI - [Tetanus in a drug addict and HIV carrier patient]. AB - We report the resuscitation of a woman with a severe tetanic process, dependence on drugs and acquired immunodeficiency syndrome. During her course, the patient presented high hemodynamic lability and supraventricular and ventricular ectopic beats. Impairment of oxygenation and ventilation led to tracheotomy and controlled ventilation for 25 days. Then, intermittent mandatory ventilation was initiated and maintained for 15 days. The patient was extubated. Partial pressure of oxygen in the arterial blood was 73 mmHg and PaO2/FIO2 was 183; she had a sepsis of pulmonary origin. High doses of sedative and analgesic agents (diazepam, 40 mg/hour and morphine, 2.5 mg/hour) were required. We believe the acme of the process was on days 13 and 15 during her stay at the resuscitation unit. We conclude that neither the symptomatology nor her course nor the treatment differed from other severe forms of tetanus treated by us. The infective process did not fit into what would be expected in an immunodeficient background. PMID- 2098884 TI - [Reflex response to laryngoscopy and tracheal intubation]. PMID- 2098885 TI - [Necrosis of the hand produced by cannulation of radial artery]. PMID- 2098886 TI - [Hemolytic transfusion reaction due to osmotic lysis]. PMID- 2098887 TI - [Glucose-6-phosphate dehydrogenase deficiency: anesthetic implications]. PMID- 2098888 TI - [Anti-cardiolipin antibodies and other immunological disorders in patients with systemic scleroderma]. AB - A total of 104 patients with scleroderma were examined. Anticardiolipin antibodies were detected in 37.5 per cent of the patients with systemic scleroderma and in 3 per cent of healthy individuals; they were more often detected in 46.8 per cent of the patients with diffuse affections of the skin, atherosclerosis, Raynaud's syndrome accompanied by ulcero-necrotic affections of the skin as compared to patients with restricted affections of the skin (sclerodactylia and focal scleroderma)--29.8 per cent. No significant changes in the frequency of detecting a rheumatic factor, antibodies to Scl-70 were revealed in subgroups of patients with scleroderma, positive and negative anticardiolipin antibodies. Of the greatest interest is a significant difference in levels of C reactive protein which were high in half of the patients with anticardiolipin antibodies. Anticentromere antibodies were detected twice as more often in patients without anticardiolipin antibodies that corresponded to systemic sclerodermia with minimum involvement of the skin into the pathological process. It is suggested that ulcero-necrotic affection of the skin in systemic sclerodermia is associated with C-reactive protein but it is not of an immunocomplex nature. PMID- 2098889 TI - [Local capillarotrophic insufficiency syndrome in patients with osteoarthrosis deformans (polarographic and thermographic data)]. AB - The condition of microcirculation in the region of the joints was studied by means of polarography on oxygen with an oxygen load and thermography on the Soviet high resolution television set "Paduga" in 30 patients with primary deforming osteoarthrosis (PDOA) and 15 practically healthy persons. Different direction shifts in the levels of supply and consumption of oxygen in the periarticular tissues in patients with PDOA were determined, a considerable drop in oxygen supply to the regions of the affected joints being noted. It has been established that thermography is a method of choice for diagnosis of secondary synovitis and other inflammatory affections of the joints. PMID- 2098890 TI - [HLA antigens in juvenile rheumatoid arthritis]. AB - Antigens of I class HLA system (locus A and B) were investigated in 67 patients of Latvian nationality suffering from juvenile rheumatoid arthritis (JRA). Associations of HLA antigens with juvenile rheumatoid arthritis partially coincided with the ones revealed earlier. Typing established an increased incidence of antigen B27 (p less than 0.01) and gaplotype A2, B40 (p less than 0.01). Antigen B15 possessed a protective action with respect to JRA. Interlocus combinations demonstrated a closer association with the disease than a single antigen. The authors also revealed markers of various clinico-anatomical variants of JRA. PMID- 2098891 TI - [Detection of B-cell marker of rheumatism using monoclonal antibodies D8/17 in families of patients with rheumatism (report 1)]. AB - Results of clinico-genealogical and immunogenetic examination of 220 persons including 150 patients suffering from rheumatism and members of their families have been presented. The object of the examination was a B-cell marker carriership to be determined by means of monoclonic antibodies D8/17 with the use of the microlymphocytotoxic method. The marker carriership was detected in 96 per cent of probands-patients with rheumatism and in 40.3 per cent of their relatives and in 6.7 per cent of healthy individuals of the control group. A possible contribution of the B-cell marker to rheumatism liability was suggested. A further study of the role of the given marker in rheumatism has been found advisable. PMID- 2098892 TI - [Prospidin in the treatment of rheumatoid arthritis]. PMID- 2098893 TI - [Indicators of temporary disability in rheumatic diseases of industrial workers and the effectiveness of the therapeutic and rehabilitation measures]. PMID- 2098894 TI - [Study of economic losses caused by rheumatic diseases among adult population of Vladivostok]. PMID- 2098895 TI - [Problem of diagnostic criteria in rheumatism]. PMID- 2098896 TI - [Non-steroidal anti-inflammatory drug flugalin]. PMID- 2098897 TI - [The cimicids and their importance in public health (Hemiptera-Heteroptera; Cimicidae)]. AB - A review of the Cimicidae of importance in public health is presented. After a general morphological study, special attention is given to knowledge of the biology and ecology of bed-bugs, mainly as regards their relation to the human environment and the possibility of their role in disease transmission. The species Cimex lectularius and C. hemipterus are given particular attention and data on their relevance to questions of public health are revised. Taxonomy, biosystematic and geographical distribution are presented, the epidemiologically important groups listed and control measures discussed. The paper ends with identification keys for both adult and immature stages as well as for arthropod indoor fecal traces. PMID- 2098898 TI - Biological risks of the conservation of transfusion preparations by low temperature. AB - When the blood or bone marrow collections are provided and treated subsequently, two types of biohazards may occur. The first of them resides in bacterial contamination at collection and following manipulation. The second is represented by endengering both recipients and staff with prelevement of infected tissues. Contemporary blood collections are at most risk from the transfer of infectious hepatitis and HIV virus. Possible risk-factors are analysed from the transfer of serious infections through the use of hypothermic and cryothermic conservation as well as freeze-drying. PMID- 2098899 TI - Biological hazards in the activity of organ and tissue banks and in transplantation surgery. AB - The possibilities of infection, and other not so often occurring biohazards transmission, from the dead body or harvested organ or tissue, on the bank staff during all steps of banking and surgical usage are discussed. The opposite jeopardy originated from staff and menacing the graft is mentioned, too. PMID- 2098900 TI - Mechanical engineering problems in preserving biological objects by temperature lowering. AB - Analysis of dangers caused by mechanical refrigerating and liquid nitrogen systems used for low temperature preserving of biological material and safety measures to be adopted. Hazards are caused by moving or protruding parts of the machinery, its hot parts, noise and vibration, work in cold rooms, possible destruction of pressure vessels, refrigerant inflammation or explosion, breathing the refrigerant or its decomposition products, direct contact of the refrigerant with the skin or mucous tissues, depletion of stratospheric ozone or contamination of food-stuffs. PMID- 2098901 TI - Health care provided to persons engaged in freeze-drying and conservation of biological objects by means of low temperatures. AB - Permanent and systematical attention must be paid to the care how to protect health of workers in processes of freeze-drying and conservation of biological objects by means of low temperatures. Biohazards include also development of occupational diseases. Preventive care provided to workers is recommended in the form of admission and periodical checks. Some other own experience is presented in this paper, valid health service regulations are quoted together with recommendation how to prevent occupational injuries and secure observation of the above regulations by the employer organizations. PMID- 2098902 TI - Duraplasty with pretreated freeze-dried sterilized human dura mater. AB - Different collagenic tissues, such as allogeneic fascia lata, dura mater and xenogeneic pericardium preserved by deep freezing or freeze-drying and packed in National Blood Service jars have been used with good clinical results in duraplasties performed at the Department of Neurosurgery, University Hospital at Hradec Kralove since 1956. In 1986 a new technology of preservation of the human dura mater was elaborated by the Tissue Bank at Hradec Kralove. The implant is pretreated, freeze-dried, wrapped in two plastic bags or Steriking see-through peel-packs (Wipak Medical, Finnland) and sterilized by gamma radiation or ethylene oxide gas. Its advantages are in simple storage in operating rooms and in opportunity to choose an ideal graft with regard to its shape, size and plasticity. No rehydration is needed before the clinical use. The total of 30 grafts in 30 patients (15 children and 15 adults) have been implanted successfully since 1987. Most duraplasties were performed in the posterior cranial fossa and on the brain convexity. In these situations an intradurally burying of the graft edges and atraumatic continuous suture is recommended. PMID- 2098903 TI - Fibrinolytic activity of human brain. AB - Authors studied the fibrinolytic human brain activity using the fibrin film in order to determine the location of tissue plasminogen activators. An amount of 20 human brains has been evaluated issued from cadavers with no signs of cerebral disease when alive. Most high concentration of plasminogen activators was evidenced in samples from plexus chorioideus and pia mater, while the fibrinolytic activity of grey and white matter showed uniformly low values. Large amount of plasminogen activators may be released into cerebro-spinal fluid, what can lead to a rapid fibrin clot dissolution around the aneurysm, so the rebleed may be consequential to it. PMID- 2098904 TI - Animal model of anxiety: the effect of chronic bromocriptine treatment in the genetically hypertensive rats of Koletsky type and in the normotensive rats of Wistar strain. AB - Experiments were performed in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats developed by Koletsky, i.e., in the strain where it is decreased turnover-rate of diencephalomesencephalic norepinephrine, increased CNS cholinergic activity, cholinergic supersensitivity and reduced stress resistance. The behavior in control and in drugged animals was traced in holeboard and in elevated plus-maze. In the control animals, when compared to the normotensive rats of Wistar strain, the genetically hypertensive rats of both sexes show in the first session elevated locomotor-exploratory activity, lower rate of intrassession habituation of the latter activity; in the genetically hypertensive males in the first session there is reduced percentage of time spent head dipping. The latter type of animals show lower number of entries into centre and in open arms by forepaws and by all four feet in the first session; in the first session time spent in centre and in open arms by forepaws and by all four feet is increased in normotensive males relative to hypertensive ones. Chronic Bromocriptine treatment shows in all traced parameters strain dependence. The drug only in the genetically hypertensive rats reduced total time of locomotor exploratory activity in both sessions, elevated rate of intrasession habituation of locomotor-exploratory activity in both sessions, elevated directed exploration in hole-board in both sessions, alleviated aversion towards open space and height in the elevated plus-maze in both sessions. PMID- 2098905 TI - Animal model of anxiety: effect of chronic diazepam treatment in the genetically hypertensive rats of Koletsky type and in the rats of Wistar strain. AB - Experiments were performed in the adult normotensive rats of Wistar strain in the genetically hypertensive rats of Koltsky type. Diazepam at the dose of 1 mg/kg was applied for five days. The last two days of diazepam treatment the behavior of the animals was traced in holeboard and in the elevated plus-maze. In the control animals the genetically hypertensive rats of both sexes show elevated locomotor-exploratory activity in holeboard in both sessions, genetically hypertensive females show highest degree of directed exploration in holeboard when compared with the other groups of rats; in the elevated plus-maze the normotensive rats of both sexes show lower aversion towards open space and height in elevated plus-maze relative to genetically hypertensive rats. Diazepam only in the genetically hypertensive females increases in the second session locomotor exploratory activity and reduced the inter-session habituation of the mentioned activity. Directed exploratory activity in holeboard was by diazepam treatment elevated predominantly in the genetically hypertensive rats. In the genetically hypertensive females diazepam caused inter-session sensitization in directed exploration. Considering the number of entries in centre and in open arms of the elevated plus-maze, diazepam in both strains irrespective of sex and session caused increase. Taking into account time spent in centre and in open arms of the elevated plus-maze, the strain dependent effect of diazepam is apparent, i.e., statistical significance of its "anxiolytic" effect was attained only in the genetically hypertensive rats. PMID- 2098906 TI - Animal model of anxiety: the effect of chronic dihydroergotoxine treatment in the genetically hypertensive rats of Koletsky type and in the rats of Wistar strain. AB - The observations were carried out in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats developed by Koletsky, i.e., in the strain where is decreased turnover-rate of diencephalo-mesecephalic norepinephrine, increased CNS cholinergic activity accompanied by cholinergic supersensitivity and reduced stress-resistance. The effect of dihydroergotoxine was traced in holeboard and in the elevated plus-maze. Chronic dihydroergotoxine treatment shows "anxiolytic" effect in the elevated plus-maze (i.e., this drug alleviates aversion towards open space and height), increases directed exploration, elevates the rate of habituation of the locomotor-exploratory activity at all, and elevates the rate of habituation of directed exploration especially. The drug in the above mentioned parameters shows very expressive dependent effect, i.e., the effect being more or solely expressed in the genetically hypertensive rats of Koletsky type. The results of our recent series of experiments again suggest that is is well founded to use for the screening of the drugs with potential anxiolytic effect the genetically hypertensive rats of Koletsky type, i.e., the strain which by its CNS neurotransmitter abnormalities resembles deviations observed in the patients suffering from anxio-depressive disorders. PMID- 2098908 TI - Biohazards in pharmaceutical freeze drying. AB - Among freeze-dried drugs there are many which may imperil manufacturing personnel, e.g. cytostatic drugs possessing carcinogenic effects. Production zones must be specially adapted for handling such drugs. There are many risks endangering a freeze-drying operation--power or water supply failure, but also improperly established freeze-drying cycle. A production batch of a rare, expensive and sensitive product represents a big value; modern equipment therefore features sophisticated automation, overriding possible human error. Problem of particulate contamination is less severe with vials stoppered inside the vacuum chamber, but rubber closures still may become a source of haze. Back migration of oil from vacuum pumps may be another source. Economy of industrial freeze-drying may be much improved if freezing sequence, drying rate, adjustment of vacuum by "bleeding" nitrogen are tailored specially for each particular product. PMID- 2098907 TI - The effects of calcium channel blockers on the cardiovascular system of rabbits in vivo. AB - The effects of i.v. administration of the calcium channel blockers--verapamil (0.045 and 0.45 mg.kg-1) and Mepamil (2-methylphenyl-derivative of verapamil; 0.0445 and 0.445 mg.kg-1) on the cardiovascular system of rabbits in vivo under the paced and non-paced heart conditions were investigated. Verapamil induced--in the dose-dependent manner--a decrease in blood pressure (max. 65.2%), a significant decrease in dP/dtmax. (max. 46.0%), a bradycardia (max. 79.4%), a decrease in minute blood flow (max. 63.9 %) and stroke blood flow (max. 71.5%). The administration of Mepamil did not induce important changes in heart rate; changes in other parameters were--again in the dose-dependent manner--of a similar qualitative character as after verapamil administration, but they were quantitatively less expressed (especially marked in the effect on dP/dtmax, where the maximum decrease was only to 71.5%). The results show a less pronounced cardiodepressive activity of Mepamil compared to verapamil in rabbits. PMID- 2098909 TI - Biohazard in microbiology, virology and in work with cell cultures. AB - Possible biohazards are referred to in this report resulting from person's manipulation with microbes, viruses and cell cultures as well as risky contamination of examined biological material with the worker's microflora. Eventual intercontaminations are described throughout the hypo- and cryothermic conservation including the freeze-drying of biological material. Working security regulations are listed to conclude the report. PMID- 2098910 TI - Risks involved in large-scale freeze-drying of immunological preparations. AB - Types of biohazards occurring in processing vaccines with freeze-drying method are scrutinized. The attention is payed to risky transfer of infections from animals to human subjects as well as the onset of allergies and contaminations with alien substances, and as a result of impurity of preparation produced. Risks related to the use of freeze-drying are scrutinized in detail. PMID- 2098911 TI - Multiple peptide synthesis in research on parasitic diseases. PMID- 2098912 TI - Molecular technology: peptide epitope mapping and the pin technology. PMID- 2098913 TI - Detection of Plasmodia in acridine orange stained capillary tubes (the QBC system). AB - The sensitivity, specificity and convenience of carrying out malaria diagnosis in acridine orange stained capillary tubes using a fluorescent microscope (the QBC system) was compared to screening for Plasmodia on conventional Giemsa stained thick smears. A dilution study revealed that the QBC is able to detect Plasmodia in as low a dilution as 5 organisms per ul. The QBC system was evaluated at a district hospital in Thailand. A preliminary study of 186 patients compared the QBC system to the routine malaria screening procedure (screening up to 30 microscopic fields on a thick smear). The sensitivity of the QBC was found to be 98.9% with a specificity of 94.4%. A second combined series of 465 febrile subjects were screened by thick smear and these results were compared to the QBC. 202 were positive for malaria on both QBC and thick smear. Sensitivity in this study was found to be 99.5% (202/203) and the specificity was 94.6% (248/262). When both series were combined, there were 14 QBC malaria positives that were not detected on thick smear, and 2 QBC malaria false negatives among the 651 patients studied. The parasite densities in these cases were between 10 and 320,000 organisms/microliters. The QBC system provided only a crude estimate of the level of parasitemia. The species of Plasmodia (P. falciparum and P. vivax) were correctly identified on QBC in 78% of cases. PMID- 2098914 TI - Effect of ketotifen on the ultrastructure of the erythrocytic stages of Plasmodium yoelii. AB - The effect on the morphology of Plasmodium yoelii of ketotifen treatment was different from that of chloroquine and other antimalarial drugs. Following administration of a low dosage of ketotifen, the parasite first developed a multilamellate pellicular complex which resembled a medullary sheath and then developed vacuoles and cavitations. The development of large multilamellate whorls consisting of a pellicular structure enclosing cytoplasm was the typical change which occurred. PMID- 2098916 TI - Field efficacy of mosquito coil formulations containing d-allethrin and d transallethrin against indoor mosquitos especially Culex quinquefasciatus Say. AB - Comparative field efficacy studies of four mosquito coil formulations containing active ingredient of d-allethrin (0.19 or 0.28 w/w) and d-transallethrin (0.12 or 0.16% w/w) and blank coils without active ingredient were carried out in living rooms (mean size 54.1 m3) of residential houses in a squatter area in Butterworth, Malaysia. The major indoor biting mosquitos collected in the test site were that of Culex quinquefasciatus Say (84.7%). Mean percentage reduction of blank coils, coils with 0.19 and 0.28% d-allethrin and coils with 0.12 and 0.16% d-transallethrin were 29.0, 71.7, 70.9, 75.0 and 72.6%, respectively. The use of coils as a mean of personal protection against mosquitos is discussed. PMID- 2098915 TI - Quinine resistant falciparum malaria treated with mefloquine. AB - Twenty eight adult male patients with acute uncomplicated falciparum malaria which showed RI or RII responses to quinine sulfate at the dosage of 600 mg 8 hourly for 7, 10 or 14 days were treated with a single dose of mefloquine (Lariam); 25 patients received 1000 mg, 2 received 750 mg and 1 received 500 mg. The initial response was good; there was no RII or RIII response. Three patients were lost to followup. Of 25 patients who stayed in the Bangkok Hospital for Tropical Diseases where there was no malaria transmission for 28-65 days, only one patient in the 1000 mg group had recrudescence on day 21. The cure rate was 96%. Our prospective study suggests that mefloquine was effective in the treatment of quinine resistant falciparum malaria and the risk of cross resistance between quinine and mefloquine in P. falciparum in vivo is very low. PMID- 2098917 TI - An effective axenic culture system for Trypanosoma brucei rhodesiense blood stream forms in vitro. AB - An effective axenic culture system for Trypanosoma brucei rhodesiense (ILRAD 1501) bloodstream forms is demonstrated. Bloodstream forms were continuously grown in 25 mM HEPES-buffered D-MEM supplemented with 10 microM bathocuproine sulfonate (BCS), 100 microM cysteine, and 20% heat-inactivated fetal bovine serum at 37 degrees C in vitro. At the initiation of the culture, T. b. rhodesiense bloodstream forms required the presence of 0.2 IU/ml insulin and 1 mM pyruvate, while bloodstream forms were grown in the culture medium without these supplements 4 days after initiation of the culture. Under this culture condition, T. b. rhodesiense bloodstream forms increased in number to 7 to 8 x 10(6) trypanosomes/ml, by day 4 after initiation of the culture. The trypanosomes cultured in this axenic system for 150 days were typically long and slender and retained their virulence for mice. This axenic culture system is extremely useful for in vitro cloning of T. b. rhodesiense bloodstream forms in vitro. PMID- 2098918 TI - Scanning electron microscopic observations of first- and third-stage larvae and adults of Angiostrongylus costaricensis. AB - The surfaces of larval and adult Angiostrongylus costaricensis, causative agent of human abdominal granuloma, were studied by the use of scanning electron microscopy. Cuticular annulations were clearly demonstrated on the surface of larvae and adults. Differences in the appearance of alae in larval stages and in the shape of the tail at different stages of development are described and illustrated. Several aspects of morphology previously unreported for this parasite are also described. PMID- 2098919 TI - Amebiasis at an evacuation site on the Thai-Cambodian border. AB - Symptomatic intestinal amebiasis was highly endemic among the Cambodians living at Green Hill, an evacuation site on the Thai-Cambodian border between June 1987 through May 1989. Monthly incidence rates of intestinal amebiasis were determined to be inversely proportional to cumulative monthly rainfall. The highest incidence of amebic dysentery was 63/1000 in children 12-23 months old. Behavioral risk factors were investigated by conducting a case-control study. A questionnaire was administered to 73 families, each having at least one member with confirmed intestinal amebiasis within the past 3 months, and to 95 randomly selected control families having no individual with diarrhea for at least 3 months. Individuals from families with greater than 4 members were at higher risk for acquiring intestinal amebiasis. No significant differences in behavioral risk factors were identified between case and control families. Eighty-six percent of 51 water samples drawn from wells where amebiasis patients obtained their drinking water had greater than 10 coliforms/100 ml. The main route of transmission of E. histolytica was not identified, but was most likely via the fecal-oral route. PMID- 2098920 TI - The "crowding effect" phenomenon in Ascaris lumbricoides. AB - Ascaris lumbricoides worm populations were studied from 150 Filipino children (0 14 years) dewormed with pyrantel pamoate (Combantrin) or oxantel-pyrantel pamoate (Quantrel). Populations were classified according to intensity of infection: very light, light, moderate or heavy. A total of 2072 adult worms were sexed (939 males and 1133 females) and weighed. Descriptive statistics on the weights obtained from each sex were derived and one-way ANOVA was performed to compare the mean weights among the 4 intensity classes. Linear regression analysis (individual worm weight versus total worm burden) was also employed to equalize the possible influence of host factors. Statistical analysis revealed that mean weights of both sexes were significantly different and decreased as worm burden increased. This strongly suggests that the "crowding effect" phenomenon may also apply to Ascaris lumbricoides, and not only to tapeworms, as reported in the literature. PMID- 2098921 TI - The pattern of diarrhea in children in Khon Kaen, northeastern Thailand: I. The incidence and seasonal variation of diarrhea. AB - The incidence, seasonal variation and risk factors of diarrhea in children in Thailand are not well defined. The objective of this study is to identify the incidence and seasonal variation of diarrhea in a rural community. A cohort of 481 children under five years of age from 14 villages in rural northeastern Thailand was followed for 1 year, from May 1988 to April 1989. The data were collected daily by 5 participant observers who resided in the villages during the study period. During the 25,012 person weeks of surveillance, 384 episodes of diarrhea occurred; 279 episodes (72.7%) were watery diarrhea and 105 episodes (27.3%) were dysentery-like diarrhea. The incidence of diarrhea was 2.1, 1.76, 0.96 and 0.45 episodes per child per year for children aged 0-6 months, 7-12 months, 1 year and above 2 years, respectively. Males were affected as frequently as females. The average duration of illness was 4.9, 2.1, 1.5 and 0.5 days per child per year for children aged under 1 year, 1-2 years, 2-3 years and more than 3 years old, respectively. Both dysentery and watery diarrhea rates peaked for children of all ages from May to July, during the early rainy season. A second peak of watery diarrhea in the winter from November to January and was seen primarily in children less than 2 years old. The monthly incidence of diarrhea was associated with rainfall, ambient temperature and occupational behavior of people in each season. PMID- 2098922 TI - Gastrointestinal lesions in patients over 40 years of age with iron deficiency anemia and hookworm infection. AB - A prospective study of 41 patients (24 male and 17 female) aged over 40 years with iron deficiency anemia and hookworm infection was performed by endoscopy and barium enema to determine the incidence of GI lesions. Alcohol ingestion, smoking, abdominal pain, anorexia, loss in weight, bowel habit change, analgesic consumption and stool occult blood test were analyzed for their positive predictive value of GI lesions. The mean age of the patients was 62.8 years (SD = 10.1). The mean hemoglobin was 5.99 gm.% (SD = 1.9). Twenty patients (48.8%) had GI lesions. The lesions included 10 erosive gastritis, 1 erosive duodenitis, 5 gastric ulcers, 2 duodenal ulcers, 1 carcinoma of stomach and 1 carcinoma of colon. Gastric ulcer, duodenal ulcer and carcinoma were regarded as significant lesions. Abdominal pain was found in 16 of the 20 patients with GI lesions and 8 of the 21 without GI lesion (Chi square with Yate's correction, x2 = 5.78 p = 0.02). Four of the 17 patients without pain had GI lesions but only one of these 4 (5.8%) had gastric ulcer. Abdominal pain had an 80% sensitivity and 62% specificity for the positive prediction of GI lesions based on the above findings. GI investigation is recommended for all patients with abdominal pain. In those without pain, treatment of hookworm and iron therapy with follow-up may be justified. PMID- 2098923 TI - The pathogenicity of a Philippine isolate of Naegleria sp. in mice: effects of dose levels and routes of infection. AB - The pathogenicity of a Philippine isolate of Naegleria sp. was evaluated using 3 4 week-old mice as experimental animals. Results showed that only the massive doses of 10(6) and 10(7) amebae/mouse inoculated intranasally could successfully establish ameba infection in the brain and cause death after 2-6 days. The effect of the ameba on the mortality rate of inoculated mice was dose-dependent. The amebae were recovered in the brain when inoculated through intracerebral and intranasal routes and in the lungs, liver, and intestines when administered through intranasal and oral routes. By intraperitoneal inoculation, recovery of amebae was positive in all major organs except in the heart. Intravenous inoculation resulted to positive recovery in the lungs, spleen, liver, and heart. Infectivity of the ameba isolate in major organs was route-dependent. PMID- 2098924 TI - Serological and genetic characterization of bovine rotaviruses in Thailand by ELISA and RNA-RNA hybridization: detection of numerous non-serotype 6 strains. AB - A total of 62 fecal specimens positive for rotavirus were collected from diarrheic cows in Thailand in 1988 and 1989. The antigenic properties of rotaviruses in stool were examined by enzyme-liked immunosorbent assays using specific monoclonal antibodies directed at VP4, VP6 or VP7: all the bovine rotavirus strains were determined as subgroup I; none of the strains were reactive with serotype 6-specific monoclonal antibody; and different reactivities of the bovine strains with two anti-VP4 monoclonal antibodies were observed. Polyacrylamide gel electrophoresis of viral RNA exhibited three different RNA electropherotypes. In RNA-RNA hybridization experiments using cell culture adapted three strains as well as a reference bovine strain (NCDV), RNA from the Thai bovine strains showed very low homology to that from NCDV; only three or four RNA segments were hybridized between the RNAs from Thai samples and NCDV. These results suggested that bovine rotaviruses isolated in Thailand are serologically and genetically distinct from a reference serotype 6 bovine strain, NCDV. PMID- 2098926 TI - Immune response in rabbits to dengue viral proteins. AB - Antisera to all types of dengue and Japanese encephalitis (JE) viruses were raised in rabbits. The first set of rabbits was immunized with crude antigens prepared by a sucrose acetone extraction. The first generation of antisera demonstrated antibody activity towards the group specific flaviviruses, without unwanted antibody activity towards the mouse brain material. Antibody activity towards E, NS3, NS5 and NS1 could be observed by western blot/immunoenzymatic assay. Another set of rabbits was immunized with the precipitin complexes formed between antisera raised against each type of dengue, or JE viruses, and their homologous antigens. Each rabbit serum was screened again by the western blot/immunoenzymatic method, and was absorbed with other types of dengue viruses until the specific activity towards the immunized viral antigen was obtained. The last 2 bands detected on the viral antigen strip were the doublet of protein bands at Mr 67 and 71 kDa, which are the NS3 protein. The specific polyclonal antisera obtained can be used with other tests as well as the monoclonal antibody. Since absorption can lead to type specific antisera, this NS3 protein must be quite unique, it processes a type specific determinant (s) and deserves further study as a target molecule at the polypeptide level as well as at the RNA level. PMID- 2098925 TI - Dengue virus serotypic identification using suckling mouse and western blot technique. AB - The suckling mouse which is used in the classical method to detect and propagate dengue viruses was evaluated in conjunction with the western blot and immunoenzymatic methods to detect the infecting strains of dengue viruses. After intracerebral inoculation of patients' sera into the suckling mice for 7 days, the mice were examined for the presence of dengue proteins, even though the mice did not have the neurological symptoms which usually serve as an indicator for the presence of dengue infection in the mouse brain. With a blind study of a set of 12 specimens, the suckling mice could detect the virus with the same frequency as the mosquito system but in shorter time of incubation period. The whole process to identify the type of infection takes 9 days. Another important finding is the demonstration of the virion antigen in the liver. The quantity and quality of viral proteins in liver are comparable to those in the brain suggesting that the virus may replicate in the liver as well as in the brain. PMID- 2098927 TI - Primary laryngeal tuberculosis mimicking carcinoma. PMID- 2098928 TI - Global epidemiology of dengue hemorrhagic fever. PMID- 2098929 TI - Antigen and antibody detection and update on the diagnosis of dengue. AB - The diagnosis of dengue is an imperfect science. By 1983 we had sensitive isolation systems including arthropods and arthropod cell cultures, specific-and group-reactive monoclonal antibodies, and a rapid and sensitive immunoassay for IgM and IgG. Progress in the past 7 years encompasses the use of monocyte lines for primary isolation, a more rapid plaque reduction neutralization test with BHK 21 cells, labeled RNA probes to detect dengue-specific nucleic acid, and improved ELISA technology with specific synthetic and engineered antigens. PMID- 2098930 TI - Antigenic analysis of dengue virus using monoclonal antibodies. AB - Dengue viruses are classified as a separate antigenic group within the Flaviviridae on the basis of cross-reactivity in neutralization assays employing polyclonal sera. Additional serological relationships defining group, complex and type specificity between members of the various antigenic groups have also been identified with polyclonal sera in analyses using hemagglutination inhibition (HI) and complement fixation (CF) tests. With the advent of monoclonal antibodies, however, this picture has become far more complex. While the basic framework of serological relationships has been confirmed, a large number of additional cross-reactivities have been identified that suggest a much greater degree of antigenic diversity and/or relatedness than previously imagined. Monoclonal antibodies have not only been used to dissect the antigenic relatedness between flaviviruses but also in studies aimed at defining epitopes on viral proteins involved in a range of biological activities from protection to antibody-dependent enhancement (ADE) of infection. Of the ten proteins encoded by the dengue virus genome, monoclonal antibodies have been raised to six, including each of the structural proteins (C, prM, E) and three of the non-structural proteins (NS1, NS3, NS5). These antibodies have been applied to the construction of functional maps and in particular to the definition of antigenic determinants involved in protection. PMID- 2098931 TI - Pathogenesis of dengue: an alternative hypothesis. AB - This paper presents a novel but entirely hypothetical concept on the pathogenesis of the shock syndrome (DSS) associated with dengue hemorrhagic fever (DHF). Antibody-dependent enhancement (ADE) is widely thought to be central to the development of these clinical entities. Current views on the mechanisms underlying ADE centre on two major lines of thought: 1) Non-neutralizing antibodies to dengue virus (DV) can enhance viral uptake and replication in target cells (monocytes). 2) DHF/DSS are the consequences of enhanced viral replication, paired with immunopathological processes that are evoked by monocyte dysfunction and detrimental reactions caused by activated T-lymphocytes. The present hypothesis proposes, by contrast, a central role for the following processes: 1) Secondary infection of an individual who has sub or non neutralizing antibody titers against DV leads to a booster antibody response and a steep rise in antibody levels. 2) Antibodies against DV bind to and direct a selective attack of the complement system onto cells expressing viral antigens on their surface. DHF/DSS are the direct and indirect consequences of complement activation on these cells. The advanced hypothesis, which departs from the mainstream of "immune enhancement" concepts, can easily be tested by experimentation. PMID- 2098932 TI - Suitability of nurses and school-teachers as oral health educators in Gazankulu- a pilot study. AB - This study investigated the suitability of nurses and teachers as potential oral health educators. The assessment was based on a concept of suitability that embraced biological and psycho-social variables. These included oral health status, knowledge, attitudes and reported oral health behaviour. The study population comprised 48 nurses and 43 school-teachers. DMFT of nurses was 4, 6 and teachers 2,5. More than 80 percent of both groups required some form of periodontal treatment. An adequate but basic knowledge of the causes and prevention of oral disease was demonstrated. More that 50 percent of both groups did not visit a dentist annually. Attitudes reflected the belief that teeth are expendable and easily replaceable. In terms of the theoretical model these nurses and teachers do not meet all the criteria that define "suitable" oral health educators. The findings of the present study have provided a profile which has highlighted certain deficiencies in knowledge, attitudes and behaviour. Further research using this model requires the inclusion of motivational and interest variables. PMID- 2098933 TI - Suitability of teachers as oral health educators. AB - In view of the vast number of people to whom dental services are not accessible, the WHO has proposed the use of lay persons as health educators. This study investigated the suitability of teachers in Gazankulu to fulfil this role. Two hundred and twenty-two teachers from the district of Letaba provided the study population. Oral health status was measured and a structured questionnaire was administered which probed areas such as knowledge, attitudes, reported behaviour, motivation and interest. The mean DMFT was 4,7 with an M component of 3,6 while 28 per cent of subjects were free from caries. The majority of subjects expressed an adequate knowledge of causes of decay, frequency of brushing, dental visits and fluoride. In terms of oral health status and knowledge the teachers appear to be suitable as oral health educators. With regard to utilisation of services, their self-assessment, attitudes, motivation and interest, several contradictions exist, which raise some doubt about their suitability. This however, can be minimised by adequate training and does not preclude the utilisation of teachers as oral health educators, especially in the context of the social reality in Gazankulu. PMID- 2098934 TI - Provision of "comprehensive dental care" in various dental schools. AB - The purpose of this survey was to solicit information about comprehensive dental care (CDC) programmes in various dental schools. Seventy-four schools responded to a questionnaire which sought information about a range of topics pertaining to CDC. The 19 questions used were categorized under the following headings: implementation and success; physical nature of clinics; staffing; and, student involvement. The diverse nature of the responses is thought to be an expression of differing philosophies and of the presence of numerous constraints to the introduction of CDC. The various approaches to CDC make it very difficult to gauge the relative merits of the many systems reported. It appears from this study that departments will continue to play an important role in preparing students to participate in CDC programmes and that it would be safer to introduce students to CDC during the final year of study. PMID- 2098935 TI - Risk of HIV to the dental practitioner. PMID- 2098936 TI - Age differences in the stress patterns of dentists. AB - The present study is a comparison of the stress patterns of older and younger dentists in private practice. Dentists responded to a questionnaire which sought to elicit their responses to a number of situations and events that typically occur in their professional lives. These included financial difficulties, patient management problems, time issues and uncertainty about their professional status. The groups compared were dentists over 54 years (n = 36) with dentists below the age of 35 years (n = 41), where both the frequency and intensity of their responses were measured. The findings suggested that overall, the older dentists are less stressed than their younger counterparts. Some issues, those concerned with finance and patient-management, appear to affect both groups more or less equally, which suggests that these issues are of global, rather than specific concern. From a theoretical point of view, the findings tend to contradict the generally-held belief that getting older is automatically accompanied by degeneration and problems of adaptation to life changes. On the contrary, seemingly favourable adaptation and low levels of stress are evident in most of the older respondents. PMID- 2098937 TI - Amelogenesis imperfecta: multiple impactions associated with odontogenic fibromas (WHO) type. AB - Three types of amelogenesis imperfecta (AI) are recognised, namely hypoplastic, hypomature and hypocalcified varieties. We report on two cases of hypoplastic AI, the type which occurs most frequently. Both patients presented with multiple impacted permanent teeth. Odontogenic fibromas of the WHO type were found to be associated with the crowns of all the impacted teeth and are considered to have prevented normal eruption. Dentinal dysplasia found only in the furcation area of the multirooted impacted teeth was evident. The macroscopic, microscopic and radiological appearance of the affected teeth, pericoronal lesions and interradicular dentinal dysplasia are described, and the most likely origins of the odontogenic fibromas and calcifications observed, are discussed. PMID- 2098938 TI - Preservation of the quantity of lactobacilli in samples from the oral cavity. AB - Transport media for the preservation of streptococci from oral samples have been described, but a suitable transport medium for the preservation of lactobacilli in oral samples is yet to be established. In this study MRS, ROGOSA, and modifications of these media were evaluated as transport media for the quantitative preservation of oral lactobacilli. Results indicated a survival of ca. 100 per cent oral lactobacilli for both media when stored at 4 degrees C for up to 72 h. A decrease in the survival rate was obtained upon storage at -196 degrees C and growth occurred upon storage at 20 degrees C. It was evident throughout that carbohydrate-free modifications of both media best supported the quantitative survival of oral lactobacili. Carbohydrate-free modifications of both MRS and ROGOSA are therefore recommended as preservative transport media for the quantity of oral lactobacilli in oral samples for limited time periods. PMID- 2098939 TI - Bilateral oblique facial cleft--tissue expansion with primary reconstruction. AB - The oblique facial cleft may present as a cutaneous and/or an osseous cleft, with or without a cleft lip, and with or without a cleft palate. This particular case was born with complete bilateral cutaneous-osseous oblique facial clefts which extended from the oral cavity to the eye sockets with anophthalmia on the right side. The first surgical intervention included a midline nasal skeleton alignment and bilateral cleft lip and alveolus reconstruction. Urinary Foley catheters were used as facial tissue expanders and inserted adjacent to the oblique facial clefts. The second surgical procedure consisted of a partial pyramidal Le Fort II osteotomy for an inferiorly displaced nasal maxillary skeleton and a rotation and advancement of the cheek as a flap for reconstruction of the palpebral cleft and inner canthus. PMID- 2098940 TI - [Analysis of 33 patients with burning mouth syndrome]. AB - Thirty-three patients complaining of a burning mouth were investigated for deficiencies which might cause the symptoms. No deficiencies could be demonstrated. They were also questioned on their state of mind in the preceding period and their daily intake of medicine. More than half described their state of mind as normal. Benzodiazepines was the drug group used most. A treatment protocol for these patients is described. PMID- 2098941 TI - Comparative diagnosis of specific temporomandibular joint arthralgias by means of computerised tomography. AB - In general, it is not easy to make the correct clinical diagnosis of a specific internal derangement of the arthralgias. The ten types of internal derangements, with desynchronisation between the meniscus and the condyle, may present clinically with localised sounds, such as clicking, grating and grinding, or without any sounds. Computerised tomography is one of the few non-invasive aids used for obtaining a more accurate diagnosis of arthralgia or anatopathological problems of the joint. The sagittal and coronal alignment of the skull and joint in the gantry, the specific highlighting of the meniscus and use of different types of occlusal splints, are all necessary for the accurate diagnosis of an internal derangement. The examination of 118 such joints is presented in this paper. PMID- 2098942 TI - Effect of varying processing solution temperature on radiographic contrast and relative film speed of dental film. AB - The aim of this study was to determine the effect of a stepwise rise in temperature on three film types processed in six different processing solutions and to identify the combinations of film, solution and temperature which produced the best results in terms of radiographic contrast and relative film speed. The film types were Agfa Dentus M2, Flow X-ray and Kodak Ultra Speed while the processing solutions were Agfa, Durr, EBX, Kolchem, MEMS and Pro-tech. An aluminium step-wedge was exposed under standardised conditions. Processing was carried out in a Durr 245L automatic processor with variable temperature settings from 25 degrees to 35 degrees C. Unexposed films were processed at each temperature setting to determine the base plus fog values. Densitometric readings were taken using a digital densitometer, and the base plug fog values subtracted from each reading. Radiographic contrast and relative film speed were calculated and the data obtained subjected to statistical analysis using Duncan's Multiple Range Test. It could be concluded that, as the processing solution temperature rose from 25 degrees C to 35 degrees C, both radiographic contrast and relative film speed increased. The highest radiographic contrast was obtained by Agfa film in Kolchem solution at 35 degrees C, while Kodak Ultra Speed film in MEMS solution at 35 degrees C gave the highest relative film speed. An acceptable base plus fog level of 0.25 was obtained in the case of Agfa film in combination with Agfa, Durr and Pro-tech solutions and Flow X-ray film with Durr solutions. All the other combinations produced a base plug fog level higher than 0.25. PMID- 2098943 TI - Orthodontic treatment in general dental practice in South Africa. AB - There is an increased demand for orthodontic treatment in South Africa and the general practitioner is showing increasing interest in implementing orthodontic treatment in private practice. The present study investigated the scope of orthodontics undertaken by the private practitioner in South Africa, in order to study the desirability of more comprehensive undergraduate training in orthodontics and continuing education for general practitioners. A questionnaire was completed by 1,012 dental practitioners. The data were analysed statistically by means of the SAS software. The results indicated that general practitioners are engaged in a wider range of orthodontic treatment modalities. The competence of the general practitioner to treat the spectrum of dental malocclusions and the ability of continuing education courses to produce "instant general-practitioner orthodontists", remains a cause for concern. Curricular restructuring requires realistic surveying of sociodemographics, including changes in birthrate and the need and demand for orthodontics in the unique South African situation, if it is to be the goal of the profession to strive for the highest standards. The educational institutions in South Africa should give attention to realistic orthodontic curricular restructuring in view of the changing dental treatment patterns currently being experienced in this country. PMID- 2098944 TI - Aesthetic alternative to conventional posterior restorations. AB - In South Africa silver amalgam is still widely used as a filling material. Concern about the safety of the patient and dental personnel does exist, however, due to the possibilities of mercury poisoning. Demands for aesthetic dentistry are increasing in response to wider media coverage. More and more patients are asking their dentists to replace acceptable and faulty amalgam restorations with aesthetic alternatives. Such alternatives to conventional posterior restorations are discussed and their respective merits are considered. PMID- 2098945 TI - [Contrast between retrusive contact position and intercuspal position: cephalometric study]. AB - In this study the differences between the retrusive contact position and the intercuspal position of 20 patients were compared with their interocclusal distances and their gonial angles. A highly significant negative correlation between interocclusal distances and the differences between retrusive contact and intercuspal positions could be demonstrated. A positive correlation was also found between the gonial angles and the differences between retrusive contact an intercuspal positions. A negative correlation between gonial angles and interoclusal distances could also be demonstrated. PMID- 2098946 TI - [General dental practice as a qualification for admission to specialization in dentistry]. AB - Questionnaires were mailed to registered specialists in dentistry with the purpose of soliciting their views on the SAMDC's requirement that at least two years in general practice should be a prerequisite for specialization in dentistry. The views of a group dentists in general dental practice were also obtained. The majority of respondents approved of the requirement. Time spent in general dental practice and age (1989) were also obtained. The purpose was to determine whether these factors would influence the specialists' proposals for the requirement of general dental practice experience. PMID- 2098947 TI - [Comparison of knowledge of subject content with the written text objectives in final year of dental course]. AB - To ensure validity of student assessment, there should be a positive relationship between the profile of the study content, and the profile of the learning objectives to be tested. This study has indicated that, in the 8 subjects which were analyzed, this relationship varied from a weak positive (r = 0.13), to a strong positive (r = 0.914). It can also be concluded that, depending upon the nature of the subject, 50-70 per cent of questions on the memory level, would be acceptable in a written paper. PMID- 2098948 TI - [Implementation of matrix functional frame in Dental Faculty of Academic Hospital for tooth and mouth surgery, University of Pretoria]. AB - Deficiencies, characteristic of professional bureaucracies, such as poor co ordination and telescopic vision, were identified in the Oral and Dental Academic Hospital, Faculty of Dentistry, University of Pretoria. Within a hybrid, formed between this professional bureaucracy and the Department of Health Services and Welfare, lies the potential for conflict, created by the difference in mission statements of the two systems, the deficiencies of which are clearly manifested. In an effort to address the problem, an organisational structure has been developed which could function as a matrix, thereby facilitating management through optimal communication and decisions by consensus. PMID- 2098949 TI - Tuberous sclerosis: report of a case with fibromatosis of the facial soft tissues. AB - Tuberous Sclerosis (TS) is a dominantly inherited disorder which is characterised by a triad of mental deficiency, epilepsy and angiofibromas of the face. Sub- and periungual fibromas, shagreen patches usually found in the lumbosacral region and hypopigmented skin lesions are less often seen. Paraventricular calcifications, skeletal disorders and rarely, ophthalmic tumours are also described. Oral manifestations include whitish confluent nodules on the mucosa, enamel hypoplasia, mandibular cysts, and oral fibromas. A case of fibromatosis of the subcutaneous tissue overlying the angle of the mandible is described together with TS. To the best knowledge of the authors, this is the first such case reported in the literature. PMID- 2098950 TI - [Synaptonemal complexes in vaccinated mice]. AB - Synaptonemal complexes of spermatocytes I obtained from C57BL/6j male mice treated with inactivated bacterial vaccines were spread over the hypotonic phase and then were investigated using light microscope. The slides of synaptonemal complexes of mice treated with cyclophosphamide were used as positive control. It is shown possible in principle to reveal synaptonemal complex abnormalities by means of light microscopy. These abnormalities were not more frequent in vaccinated animals than in intact ones. Cyclophosphamide at doses of 100-200 mg/kg induced synaptonemal complex damage practically in 100% of cells 96 hours after the injection. PMID- 2098952 TI - [Additive, heterosis and maternal effects in various methods of crossing in swine breeding]. AB - The effects of genes with various cross methods in swine breeding have been revealed. Additive and maternal effects are determined on the basis of a great number of fattening and meat qualities. Thus, it is advisable to use the absorptive crossing. PMID- 2098951 TI - [Potential for suppression of E. coli rplj gene expression by antisense RNA]. AB - Construction of the recombinant plasmids, containing the antisense sequence of the E. coli rplJ gene under control of lac promoter has shown their effect on the level of the detector rplJ-lacZ gene expression. PMID- 2098953 TI - [Cytogenetic activity of the pesticides cyclophos and alvison, their components and metabolites]. AB - Two new pesticide preparations of cyclophos and alvison, a number of their components, two alvison metabolites have been studied to reveal their cytogenetic activity. According to the investigation in vivo the mutagenic effect of cyclophos manifests itself only with toxic doses. Professional contacts with the pesticide don't induce chromosome mutation in human peripheral lymphocytes. The alvison preparations generate chromosome mutations in somatic cells of people and animals. The components and metabolites of alvison have shown no visible genetic activity during in vivo and in vitro experiments. PMID- 2098954 TI - [Criteria of allowance for the mutagenic effectors in the Ames test]. AB - Mutagenic activity of water pollutants on test-strains Salmonella typhimurium was studied. Results obtained from these studies were evaluated by the Dunnet method of multiple comparisons and the obtained data were compared with the value of excess of the colonies number in the experiment over control. The purpose of this comparison is to determine a ration of excess in the number of revertant colonies in the experiment above a control, under which a portion of the statistically significant results will constitute 90 per cent and more. Statistically significant results occur in 100% of cases when the number of revertant colonies in the experiment variants is 2.2 times as high as in control ones for strains TA 1535 and TA 1538, 2.0 times--for strain TA 98 and 1.8 times--for strain TA 100. PMID- 2098955 TI - [Cytogenetic changes in peripheral blood lymphocytes of oncology patients]. AB - Analysis of home and foreign literature underlies the discussion of the significance of cytogenetic variations (frequency of aberrant cells and SCE heteromorphism of C-chromatin and brittleness of chromosomes as indices of chromosome instability in oncological patients. PMID- 2098956 TI - [Genetic mechanisms for the regulation of natural killer cell activity]. AB - The problems on genetic mechanisms of regulation of natural killer cells, participation of major histocompatibility complex in these processes are considered. The examples of mutations and hereditary diseases accompanied by disfunction of the natural killer activity are presented. It is supposed that genetic predisposition of natural killer activity depression can promote an increase in the risk of malignant and autoimmune diseases. PMID- 2098957 TI - [Ultrastructural examinations of HeLa cells exposed to cadmium ions]. AB - Destructive changes in cadmium-treated HeLa cells affecting practically all the cell structures and organelles, were observed. Side by side with it compensation and adaptation responses of cells, which in definite period reduced cell pathological effect of this microelement were revealed. PMID- 2098958 TI - [Comments on the current trends in virus research and the society]. PMID- 2098959 TI - [Recent advances in the transmissible spongiform encephalopathy research--with special reference to scrapie]. PMID- 2098960 TI - [Molecular biology of coronaviruses]. PMID- 2098961 TI - [Hyperbaric oxygenation in the treatment of patients with vibration disease due to local exposure]. AB - Results are reported of treatment of 69 patients with vibration disease (VB) using hyperbaric oxygenation. Treatment course--10 sessions with an exposition of 40 minutes in the main regimen. Tests for choice of treatment regimens (1.3, 1.5, 1.8 atm.) were the dynamics of subjective and objective clinical signs, indices of the peripheral hemodynamics and thermoregulation. Hyperbaric oxygen treatment in persons with signs of vibration effects (preclinical stage) using a working pressure of 1.3 atm is justified. Presence of clinical manifestations of the disease (grade I-II degree of VB severity) justifies increase of the dose of hyperbaric oxygen to 1.5 atm. PMID- 2098962 TI - [The evaluation of the purity of medicinal oxygen]. AB - Conditions are described of gaseous-chromatic analysis of inorganic mixtures contained in medical oxygen using chromatography with a detector of thermal conductivity. The relative error of determination does not exceed +/- 10%. PMID- 2098963 TI - [The structure of the morbidity among people working at computers with video display terminals]. AB - The authors analyzed data of ane examination of 407 user of video display terminals of large computer centers in Kiev and revealed high morbidity of the circulatory digestive and locomotor organs. An analysis of 878 analogous cases in the GDR revealed lower involvement of the mentioned organs. Causes are analyzed. Ways of prophylaxis are outlined. PMID- 2098964 TI - [The characteristics of the phenotype distribution of blood serum haptoglobin in coal miners]. PMID- 2098965 TI - [The structure of the morbidity with temporary loss of work capacity among female workers in the cotton industry]. AB - A comparative study of the levels of temporary loss of working capacity among females working in the cotton production industry in different working and social conditions allowed to reveal higher incidence of morbidity in this category of workers as compared with the control group and to work out a complex of measures aimed at reducing this morbidity and ensuring stable recovery. PMID- 2098966 TI - [The characteristics of the clinical course of hemorrhagic meningoencephalitis]. AB - A study is presented of 132 patients with hemorrhagic meningoencephalitis of viral, bacterial and viral-bacterial origin. Before admission to the clinic meningoencephalitis was diagnosed in 46.2% of patients. The cause of hypodiagnosis was underestimation of the clinical manifestations of the disease and anamnesis findings at the prehospital period. In 15.9% of patients the disease began with psychotic disorders. Lethality was 23.48%. PMID- 2098967 TI - [The hemodynamic, tissue oxygen balance and muscle blood flow indices of patients with multiple sclerosis]. AB - The central and peripheral hemodynamics, oxygen tension in the muscles and tissue local blood flow was studied in the course of complex treatment in 37 patients with multiple sclerosis. Remissions of the disease were characterized by the hyperkinetic type of blood circulation, increased vascular tone of the peripheral vessels against the background of an increase of oxygen tension in the muscles and enhancement of local tissue blood flow in the tissues. Severe forms of the disease, progressing course and exacerbation were distinguished by the hypokinetic type of blood circulation, dystonic and atonic state of the extremity blood vessels, reduced pO2 and local blood flow in the tissues. PMID- 2098968 TI - [The microcirculatory function in the chronic HBs-antigen carrier state]. AB - The authors discuss the problem of widely spread chronic carrier state of HBs antigen by healthy persons. The majority of antigen carriers show both moderate clinico-biochemical and ultrasonic signs of chronic liver involvement, and different disorders of the microcirculation which are formed in conditions of prolonged persistence of the virus of B hepatitis in the body. Early diagnosis of generalized disorders of the terminal blood circulation in antigen carriers may be useful in the determination of pathogenetically substantiated treatment tactics and prognostication of unfavourable outcomes of chronic HBs-antigen carrier state in preclinical period of the disease. PMID- 2098969 TI - [Intravascular coagulation in lung diseases (a review of the literature)]. PMID- 2098970 TI - [The school of R. E. Kavetskii, Academician of the Academy of Sciences of the Ukrainian SSR, and its scientific ties]. PMID- 2098971 TI - [The efficacy of piracetam in treating patients with chronic bronchitis and concomitant atherosclerosis]. AB - The nootropic agent pyracetam was used in patients suffering of chronic bronchitis associated with concomitant atherosclerosis. Pyracetam was administered intravenously in saline solutions. It was found that the group of patients receiving pyracetam revealed earlier normalization of clinico-laboratory indices. Pyracetam also produced immunocorrective and antioxidant effect resulting in normalization immunity values and activity of lipid peroxidation. PMID- 2098972 TI - [The reactivation of pulmonary tuberculosis after effective chemotherapy using rifampicin]. AB - The authors present an analysis of dynamic five-year follow-up of 141 patients with freshly detected destructive pulmonary tuberculosis that received treatment with isoniaside and rifampicin in combination with other drugs. It was found that reactivation of pulmonary tuberculosis with the use of rifampicin is observed in 11 +/- 5% of patients and is accompanied by phenomena of not infrequently marked intoxication and chest symptoms and complaints. The importance of timing the main course of chemotherapy (not less than 12 months) and regular prophylactic autumn spring course of treatment in the prophylaxis of reactivations of pulmonary tuberculosis. PMID- 2098974 TI - [Sensitization to fungi of the genus Candida in tuberculosis patients]. AB - Allergic diseases in patients with tuberculosis occur three times more frequent than in the nontubercular population. Drug-related allergy is most frequent. The causes of allergy in this contingent of patients are diverse. Of one them is, apparently, high frequency of sensibilization to Candida fungi determined by skin tests and immunothermistography. This problem deserves a more detailed investigation. PMID- 2098973 TI - [The inactivation of glucocorticosteroid hormones by rifampicin when it is used intermittently]. AB - The content of cortisol was examined radioimmunologically in 60 patients with pulmonary tuberculosis with the purpose to evaluate the inactivating effect of rifampicin on exogenous glucocorticoid hormones. Separate administration of hormones and rifampicin did not effect changes of endogenous cortisol indicating increased metabolism of glucocorticosteroids. Separate administration of hormones and rifampicin does not allow to avoid the inactivating effect of rifampicin on exogenous glucocorticosteroid hormones. Rifampicin did not change the level of endogenous cortisol. PMID- 2098975 TI - [Nifangin in the combined treatment of chronic cor pulmonale]. AB - The effect of niphangin (calcium antagonist) on the hemodynamics, gaseous exchange and course of the disease was studied in 65 patients with chronic obstructive bronchitis complicated by cor pulmonale. Synchronous registration of ECG, PCG, tetrapolar rheography, phlebography. It was found that niphangin used in the complex treatment of cor pulmonale allowed to improve the gaseous exchange, central and peripheral hemodynamics and effected favourably the course of the disease. PMID- 2098976 TI - [The dynamics of the immune system indices in myocardial infarct patients]. AB - Patients with acute myocardial infarction show an increase of IgA and IgG, while IgM concentration showed no significant changes both at the onset and end of the disease. The level of circulating immune complexes increased essentially in patients with myocardial infarction; indomethacin furthers improvement of humoral and cellular immunity. PMID- 2098977 TI - [The use of multiprogrammable cardiac electrostimulators for treating brady- and tachyarrhythmias in patients with ischemic heart disease]. AB - Examined were 54 patients with different disorders of the cardiac rhythm with an implanted programmed electrocardiostimulator (ECS-200). The authors worked out methods and criteria of choosing individual regimes of electrostimulation, evaluated their effect on the severity of stenocardia and grade of circulatory insufficiency. The threshold frequency of stenocardia is of major significance in determining the optimal frequency of electrostimulation for patients with stable atrioventricular block. For patients with sinus node weakness and transitory atrioventricular blocks the criteria of choice of electrostimulation parameters is maximum maintenance of the sinus node rhythm with a frequency of not less 50/min. PMID- 2098978 TI - [The cholesterol and lysophospholipid content of the plasma and blood cells in patients with stable stenocardia of effort]. AB - A study of 13 patients with stable exertion stenocardia and a positive bicycle ergometry [correction of veloergometric] test revealed an activation of the thrombocytic lysoform factors (lyso-FAT) along with reduction of cholesterol lipoproteids of density activity of lecithincholesterolacyltranferase. Increase of lyso-FAT is associated with accumulation of cholesterol and lysophosphatidylcholine in thrombocytes and erythrocytes. The participation of lyso-FAT in the pathogenesis of stable exertion stenocardia is suggested. PMID- 2098979 TI - [The indices of the cerebral hemodynamics in patients with juvenile hypertension and different types of blood circulation]. AB - A study of 100 patients with juvenile hypertension (JH) revealed a dependence between the character of changes of the cerebral vessel tone and type of central hemodynamics (TCH). Patients with the hypokinetic TCH show more frequently the vasospastic form of cerebral circulation (FCC) while the vasodilation FCC was observed rarer. The vasodilation FCC prevailed in patients with hyperkinetic TCH while the vasospastic was not observed. Normotensive FCC showed a similar frequency in patients with hypo- and hypertensive TCH. In patients with vasospastic FCC and hypokinetic TCH the drug of choice was nifedipin while in patients vasodilatation FCC and hyperkinetic TCH this was propranolol. PMID- 2098980 TI - [The structural-functional characteristics of the erythrocyte membrane and the atherosclerotic process]. AB - The content of glycoproteids in erythrocytic membranes and the membrane permeability was studied in 155 patients with atherosclerosis. It is recommended to use values of reduction of the content of glycoproteids in erythrocytic membrane and indices of membrane possibility in the clinical practice with the purpose of a more objective characterization of clinical variants of atherosclerosis, evaluation of the severity of its course and diagnosis of complications. PMID- 2098981 TI - [The anticoagulant therapy of patients with dilated cardiomyopathy]. AB - Complex treatment with direct and indirect anticoagulants and deaggregants carried out in 41 patients with dilated cardiomyopathy produces a significant positive effect on the condition of plasma hemostasis allowing to control the signs of hypercoagulation changes of the general coagulation, fibrinogen-like and antiheparin activity leading to normalization of fibrinolysis of the euglobulin plasma fraction. Prolonged intake of indirect anticoagulants furthers reduction of development of thromboembolism by 12.1%. PMID- 2098983 TI - [Experience in using hemosorption in treating patients with rheumatoid arthritis]. AB - Hemosorption was included in the complex treatment of 30 patients (age: 25-50 years) suffering of rheumatoid arthritis. It was found that the most sensitive laboratory tests of treatment efficacy were erythrocyte sedimentation rate, reduction of the level of gammaglobulins. Clinical improvement was pronounced as result of hemosorption treatment. PMID- 2098982 TI - [Mycoses of the lungs (a lecture)]. PMID- 2098984 TI - [The thrombocyte link in blood-coagulation homeostasis in patients with systemic lupus erythematosus]. AB - Data are reported of changes of the thrombocytic link of hemostasis in 168 patients with systemic lupus erythematosus. Essential changes were found of the coagulating and fibrinolytic properties of thrombocytes, the severity of which is related to the activity of the pathological process. It is shown that thrombocytopathic changes may be adjunctive criteria for determination of the intravascular coagulopathy. PMID- 2098985 TI - [The clinico-morphological parallels in diffuse connective tissue diseases]. AB - The authors present an investigation of the clinical and morphological signs and symptoms of diffuse diseases of the connective tissue in 27 of 50 examined patients. For verification of connective tissue disease it is recommended to carry out early histological examination of the biopsy specimens. The biopsy material should be adequately taken with consideration of the area and depth of involved tissue. PMID- 2098986 TI - [The clinico-biochemical blood indices of patients with cerebral atherosclerosis and a history of stroke]. PMID- 2098987 TI - [The age-related characteristics of the hemodynamic indices of patients with ischemic stroke]. AB - Analyzed are the age aspects of systemic and cerebral hemodynamics in 273 patients with ischemic stroke. It was found that in young patients the eukinetic type was mainly associated with hypoperfusion of brain tissue while in the older age groups the hypokinetic type of hemodynamics prevailed and disorders of the cerebral blood circulation were manifested in hypo- and hyperperfusion of the brain tissue. PMID- 2098988 TI - [The pathogenesis of secondary hypersplenism in portal hypertension (a review of the literature)]. PMID- 2098989 TI - [The functional activity of the natural killers during the experimental treatment of hemoblastoses]. PMID- 2098990 TI - [Kidney involvement in multiple myeloma]. AB - Renal function, reserve capacities of the urinary tract and mechanism of development of chronic renal failure (CRF) in multiple myeloma (MM) were studied in 40 patients. Routine methods and ultrasound renal examinations were carried out. It is shown that the main causes of CRF in MM are hyperproteinemia and paraproteinemia. It is emphasized that sonography of the kidneys is a valuable and informative method allowing to determine renal size, evaluate the state of parenchyma, reveal disorders of the urodynamics of the upper urinary tract. PMID- 2098991 TI - [A crystallographic method in the diagnosis of kidney diseases]. AB - Structural aspects of copper chloride crystallization of the urine of patients with pyelonephritis and glomerulonephritis were studied by electron microscopy. It was found that admixtures of urea, creatinine, potassium and, possibly, sodium contained in the urine of patients initiate the formation of copper chloride crystals of different sizes, their shape changes, dendritic and spherolithic crystallization occurs. Results may be used as supplementary differential diagnostic signs of glomerulonephritis and pyelonephritis. PMID- 2098992 TI - [The indices of pancreatic incretory activity in patients with chronic pancreatitis and disordered carbohydrate metabolism]. AB - Insulinemia, concentration of C-peptide and glucagon in the blood was studied in chronic hepatitis patients showing moderate tolerance disorders to glucose and diabetes mellitus developed against the background of chronic pancreatitis. Both groups showed hyperglucagonemia. Basal hypoinsulinemia and reduction of the C peptide level revealed only in patients suffering of chronic pancreatitis with secondary diabetes mellitus. Reduced reaction of beta-cells of the pancreas to physiologic stimulation by pancreosozymin were observed also in less significant disorders of tolerance to glucose. The authors discuss the significance of changes in the sequential development of different degrees of disorders of the carbohydrate metabolism in patients with chronic recurrent pancreatitis. PMID- 2098993 TI - [The immunological aspects of chronic pancreatitis]. AB - The immunological status was investigated in 200 patients with chronic pancreatitis. Recurrent pancreatitis was characterized by marked autosensitization to pancreatic tissue, latent pancreatitis forms--by a high level of immune complexes and blood serum immunoglobulins, the painful form--by minimal resistance disorders. Established were clinico-immunological parallels between the frequency of exacerbations and degree of autosensitization, level of immune complex and yield of enzymes. PMID- 2098994 TI - [Pancreatic insular function in peptic ulcer patients]. AB - Radioimmunological assay was used to study the content of insulin and C-peptide in the blood bath in conditions of basal incretion and 1 and 2 hours after a test breakfast in 12 healthy subjects, 36 patients with duodenal ulcer and 20 patients with chronic atrophic gastritis. It was found that patients with duodenal ulcer showed an increased hormonal activity of the pancreas leading to exhaustion of its reserve capacities. In patients with chronic atrophic gastritis reserve hormonal capacities of the pancreas were maintained and somewhat elevated. PMID- 2098995 TI - [Therapeutic endoscopy in diseases of the digestive system]. AB - A study of 374 patients with ulcer disease, chronic gastroduodenitis and esophagitis allowed to distinguish three clinico-endoscopic syndromes (erosive ulcerative, irritated pylorus, regurgitating syndromes). Therapeutic endoscopic manipulations were carried out: transesophageal block of the vagal nerve, pricking of the ulcer with trimecaine, solkoseryl, oxyferriscorbone, trental and laser treatment. The results were favourable. PMID- 2098997 TI - [The physicochemical properties of the bile in biliary tract diseases (a review of the literature)]. PMID- 2098996 TI - [Intensive preoperative gamma teletherapy combined with endogenous interferon induction in the treatment of stomach cancer]. AB - The authors analyze results of combined treatment of 72 patients using preoperative intensive gamma teletherapy. Increase of 4-year survival was observed only in patients showing no regional metastases and equalled 18.7%. The authors worked out a method of preoperative radiation treatment against the background of induction of endogenous interferon by curantyl. The course of radiation therapy was carried out in association with a 2-3 times increase of the interferon levels in the blood and was accompanied by a reduction of the immunodepressive effect of gamma teletherapy on the body. PMID- 2098999 TI - [The osmolarity and incompatibility of solutions for injections and infusions]. PMID- 2098998 TI - [The effect of insulin on the lipid composition of the erythrocyte membranes of diabetics]. AB - A study is presented of the dynamics of components of lipid spectrum of erythrocytic membrane in insulin-dependent type of diabetes mellitus against the background of traditional types of treatment (Porcine insulin and insulin-zinc suspension) and use of monospike and monocomponent insulins. Insulins of high purity were found to produce a normalizing effect on the disturbances of the lipid composition. Thus, cholesterol indices normalized in 2-3 months. The level of general phospholipids and dien conjugates improved as well. The changes were accompanied by positive changes in the fraction ratio of phospholipids while disorders of the fraction of phosphatidylcholine remained abnormal and low values phosphatidylinosite were registered. PMID- 2099000 TI - [Transesophageal echocardiography--a method of evaluation of the aortic and mitral valves]. AB - Transoesophageal echocardiography (TEE) is a new diagnostic method introduced for clinical practice about 1985. The method is particularly useful for the evaluation of the aorta and mitral valves. Twenty-seven patients with pathological changes of the valves of the left side of the heart were studied. In all patients the result of transthoracic echocardiography--TTE was non-diagnostic due to obesity, emphysema, deformity of the chest. In TEE diagnostic findings in the structures of the chest were obtained, their morphology and function were assessed, the clinical diagnosis was confirmed or verified. TEE was found to be useful in the evaluation of the valves, making possible establishing of correct diagnosis, especially in cases in which TTE was insufficient for providing of adequate information. PMID- 2099001 TI - [Hypertension in men with ischemic heart disease]. PMID- 2099002 TI - ["Hepar"--the clinical computer system and its diagnostic and didactic use]. AB - The possibilities of application of the "Hepar" computer system in medical didactics are discussed. The usefulness of hepatological diagnosis assistance with information++ systems is described and the multistage schema of diagnostic management is presented. In the conclusions the advantages of this system in medicine teaching is stressed and its usefulness in clinical practice is outlined. PMID- 2099003 TI - [The main objectives in using informatics in medicine]. AB - The costly application of informatics in practical medicine should be associated with unequivocal clear motivation. Three important problems are presented whose solution is possible only by computer use: integration of health information on each citizen in the country with recording of this information in a modern carried which is possessed by each patient, wide availability of modern medical computerized medical documentation for research and statistical analysis, and computer-assisted rational economics of health care services. PMID- 2099004 TI - [Is amalgam harmful to patients?]. AB - Toxicological data are presented which suggest that amalgam dental fillings containing mercury are a source of minimal but continuous exposure to mercury. However, no documented clinical and epidemiological observations are present as yet which could demonstrate the harmful effect of this exposure. PMID- 2099005 TI - [Surgical pathology of the greater omentum]. PMID- 2099006 TI - [A case of sporadic hypokalemic form of familial periodic paralysis]. AB - A case is reported of sporadic hypokalemic form of periodic paralysis, calling attention to the presence of certain rare signs, that is bilateral facial palsy and speech disturbances. The most modern reports on the aetiology and pathogenesis of periodic paralysis are discussed. PMID- 2099007 TI - [Secondary Sjogren's syndrome]. PMID- 2099008 TI - [Contribution of pathology to diagnosis of fibrosing lung diseases]. AB - The main criteria for the morphologic diagnosis of fibrosing lung disease are the type of inflammation, the localization of the lesion within the lung, and the microtopographic pattern of inflammation and fibrosis. Among the microtopographic patterns six types (perilobular, intraalveolar, alveoloseptal, bronchiolitic, vasculitic, bronchiolectatic), all corresponding to pathogenetic mechanisms can be recognized. Mainly one of these basic patterns is realized in sarcoidosis, histiocytosis X and shock lung. In other diseases a combination of two or more patterns may occur. The microtopographic pattern can be shown best in open biopsies after unfolding of the lung tissue. The findings in bronchoalveolar lavage do not reflect the real composition of the inflammatory infiltration of the lung tissue, and especially T-lymphocytes are usually overrepresented. PMID- 2099009 TI - [Endoscopic biopsy diagnosis of diffuse interstitial lung diseases]. AB - Morphological material is indispensable for the diagnosis of diffuse interstitial lung diseases. In more than 80% of the cases the making of the diagnosis is successful with the bronchological methods of transbronchial lung biopsy and broncho-alveolar lavage. The application of the thoracoscopy with aimed collection of tissue establishes the diagnosis in more than 90%. Open surgical lung biopsy (98% of making a specific diagnosis) and perthoracic lung biopsy complete the number of diagnostic methods. PMID- 2099010 TI - [Pulmonary histiocytosis X]. AB - Pulmonary histiocytosis X is a histiocytic granulomatosis of yet unknown etiology and of partial immunopathogenesis. The incidence ist about 5% compared to sarcoidosis. Almost all patients are smokers, the age peak lies between 20 and 40 years. Leading symptoms are non-productive cough and dyspnea, often it is only detected radiologically by chance. The x-ray shows bilateral nodular, later reticular changes. The characteristic ring figures may be detected only by tomography. Until recently diagnosis was made exclusively by lung biopsy, but now bronchoalveolar lavage may be already diagnostic. Early corticosteroid therapy seems to prevent the progression to the fibrotic-bullous end-stage in almost all cases. PMID- 2099012 TI - [The occupational spectrum in alveolitis and pulmonary fibrosis]. AB - The professional spectrum was analysed in 898 patients with ascertained alveolitides and lung fibroses. Most frequent were fibroses in occupations from agriculture and forestry (167 = 18.6%). Then followed workers in metal (119 = 13.3%), commerce and supply (69 = 7.7%), transport (46 = 5.1%), economic management (46 = 5.1%), building trade (42 = 4.7%) and textile workers (34 = 3.8%). The proportion of the other professional branches was lower than 3.5%. Close connections between disease and profession were seen in the employees in agriculture. The group is formed above all by farmer's lungs (exposure against hay, straw, pellets, corn, fruit, vegetables and so on) and bird-fanciers' lungs. In the other professional groups the rate of the etiologically clarified cases is essentially smaller. Particularly the metal branches are a centre for further investigations. PMID- 2099011 TI - [Diagnostic aspects of allergic alveolitis]. AB - The clinical picture of extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis is etiologically extremely multivarious and in disposed persons it can be caused by inhalation of proteins of various species of animals (in particular by avian proteins), mushrooms, bacteria, insects, thermoactinomycetes, vegetable antigens, possibly also haptens after fixation with protein produced inside the body. The inhaled dusts with a size particles of 4 to 5 micrometers which contain the disease-evoking antigens often have an activity-specific character which is expressed in the traditional names of individual forms of alveolitis (e.g. farmer's lung, mushroom-worker's lung, cheese-washer's lung, malt-worker's lung, bagassosis). However, according to our inquiries in the GDR as well as in other parts of Central and East Europe these diseases are relatively rare. In the GDR the so-called bird-fanciers' or bird-keepers' lung with a frequency of 83.4% has a supreme significance within all forms of alveolitis, followed by the farmer's lung (8.9%) and forms of alveolitis by mushrooms (7.7%). In a period of 10 years altogether 7,669 sera of patients with suspicion of alveolitis were investigated at our institute. According to the results of the immunological as well as of further paraclinical and clinical examinations in 550 cases the diagnosis of allergic alveolitis was made (459 bird fancier's lungs, 49 farmer's lungs and 42 cases of allergic alveolitis by moulds). In 88.5% of the patients who fell ill with extrinsic allergic alveolitis the disease is accompanied by a positive or very positive antigen-specific antibody formation in the blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099013 TI - [Pesticide-induced pulmonary fibrosis]. AB - Pesticide-induced lung fibrosis are very rare. Only the acute paraquat-fibrosis achieved clinical significance. Clinic, pathogenesis and therapy of this disease will be described in the main features. The so-called "Vineyard sprayer's lung" was observed up to now only in Portugal. This illness will be caused by longterm exposure in viniculture against "Bordeaux mixture" a solution of copper sulphate and slaked lime. Causuistries in the literature indicate that further pesticides especially organophosphates are possibly potent to induce lung-fibrosis. PMID- 2099015 TI - [Therapeutic possibilities in alveolitis and pulmonary fibrosis]. AB - Aetiologically, less than 50% of the alveolitides and pulmonary fibroses are clarified. A successful causal therapy by elimination of the noxae is thus possible only in several acute cases, particularly in forms of the exogenic allergic alveolitis. Usually the clinical pictures are misunderstood for a long time and are diagnosed only in advanced stages. The therapeutically influencible inflammatory changes are in such a case only slightly expressed. The more or less advanced fibrosis is not or only slightly to be influenced. Then the last way out of the difficulty of the lung and the heart-lung transplantation, respectively, the size of which, however, is limited by the small number of suitable donors. In the initial phase of the diseases in toxic and allergic-immunologic the inflammations resulting from this in the pulmonary tissue are partly to be controlled by antiinflammatorily and immunosuppressively, respectively, acting medicaments such as corticosteroids, azathioprin and cyclophosphamide. For the treatment of the lung fibrosis only D-penicillamine is at our disposal. Because of the numerous, partly considerable side effects and due to the effectiveness of the necessary long-term therapy which is only difficult to be measured there are very different opinions about the treatment with penicillamine. The enlargement of the knowledge on the pathogenesis of alveolitides and lung fibroses allows to hope that new beginnings for a therapy are found. No final judgement can be made about the efficacy of cyclosporin A and of antioxidants. PMID- 2099016 TI - [The theory of microcirculation. 3: Role of blood pressure amplitude on tissue microcirculation]. AB - The blood pressure amplitude of the pulsatile blood supply evokes elastic interactions in the tissue, in which the noncompressible tissue fluid functions as mediator of strength. The particular morphological structure round the tissue capillary gives rise to the suggestion that in the result of these interactions a tissue pump is working which supports the blood flow as well as the exchange of substances at the capillary wall. The effectiveness of this pump depends upon the blood pressure amplitude, the heart rate and upon the elastic tissue properties and can be regulated with changes of these parameters. With the help of a hydraulic model an engineer-technical solution is built up and tested which in analogy to the tissue structure functions as pump and shows the properties of elastic interactions mentioned. PMID- 2099014 TI - [Drug-induced disseminated lung diseases]. AB - Disseminated pulmonary diseases sensu stricto are interstitial lung disorders, pulmonary edema, diffuse pulmonary bleeding as well as bronchiolitis obliterans and thrombo-embolic disorders. Three important pathogenetic mechanisms are direct toxicity, allergy/immunology and idiosyncrasy; however, unfrequently essential elements of pathogenesis are unknown. The multitude of potential noxious agents implies that the clinician principally has to consider the possibility of drug toxicity in all cases of disseminated pulmonary diseases. In order to give a complete presentation summaries organized as tables could not be avoid. The most sensible measure for disseminated lung diseases is the functional parameter DLCO; it is more sensible than the conventional X-ray. The drug of choice for a treatment are corticosteroids. PMID- 2099018 TI - [Electrode-myocardium distance in transesophageal atrial stimulation]. AB - In 9 voluntary test persons with a sound heart comparative examinations were carried out to discover the optimum depth of insertion by unipolar and bipolar determination of the absolute threshold and transoesophageal derivation as well as the correlation of the optimum depth of insertion with external measurements of the body. The methods mentioned to ascertain the optimum depth of insertion are equivalent concerning the bipolar arrangement of the electrodes in the oesophagus. The average effective depth of insertion can simplified be defined. A correlation of the average effective depth of insertion concerning external measurements of the body could not be found, so that the conscientious discovering of the optimum depth of insertion is a necessity for every patient. The average value found could attain an orientating importance with the primary placing of the probe concerning the average effective depth of insertion of 37 cm. PMID- 2099017 TI - [Wegener's granulomatosis and anti-cytoplasm antibodies]. AB - 20 patients with biopsy-proven Wegener's granulomatosis (WG) and 95 control patients underwent determination of anticytoplasmic antibodies (ACPA) by the indirect immunofluorescence technique to assess the specificity and sensitivity of ACPA for WG. Of 14 untreated patients with WG, 13 were ACPA-positive. All these patients became ACPA-negative under immunosuppressive treatment. 4 patients treated with immunosuppressive drugs and 2 patients in remission after termination of therapy had a negative ACPA-test. ACPA were detected in 9 patients of the control group (two patients with Henoch Schoenlein purpura, two patients with systemic vasculitis, 2 patients with systemic diseases, and 1 patient with systemic lupus erythematodes). With that we achieved a specificity of 90.5% and a sensitivity 65.0%. In conclusion the ACPA-determination is very helpful for diagnosis and follow-up of WG. PMID- 2099019 TI - [Treatment indications of hypertensive blood pressure dysregulation (a 7-year follow-up)]. AB - The results of the present course investigations by means of bicycle ergometry over seven years on patients with vitality-limiting load hypertension in normotensive and initial situation of the borderline blood pressure, respectively, render necessary from the point of view of the authors an increase of the former indications to treatment. Situative measurement of blood pressure only at rest are hereby not sufficient and demand a bicycle-ergometric objectivation of the possible hypertensive dysregulation of blood pressure in patients with anamnestically restricted range of physical efficacy. In patients with exclusively under load increased vitality-limiting blood pressure values the ergometry represents the diagnostic method of choice. PMID- 2099020 TI - [Follow-up of surgical therapy in patients with threatened and acute myocardial ischemia for an average of 5 years]. AB - Out of a total group of 300 patients after local intracoronary fibrinolysis, systemic ultra-high short-term fibrinolysis and instable angina pectoris 73 (24% out of 300) patients, in whom acutely or in the course of the treatment a surgical therapy of their coronary heart disease was performed, were analysed. Constellations of the findings of the coronary heart disease, when according to this connection with an adequate conservative therapy on the basis of a diagnostic and therapeutic step programme in 44% of the patients an improvement of the load capacity and in 73% an improvement of the subjective well-being is to be stated. In patients with diseases of one vessel compared with patients with diseases of several vessels significantly more frequently an intraindividual increase of the bicycle-ergometric performance develops. PMID- 2099021 TI - [Viatorium medico-historicum. I. Historical sites in the region of Saxony-Prussia Anhalt]. AB - In the framework of a viatorium medico-historicum for the district of Saxony Anhalt several localities of the former border-district of Saxony, Prussia and Anhalt were marked out as places of birth of physicians and natural scientists who became known transregionally. Hereby the development of these personages was briefly outlined. PMID- 2099022 TI - [Meteorologic effects on hemorrhagic diathesis in hemophilia. 1. Demonstrating weather effects based on a complex weather phase scheme]. AB - In haemophilia frequently spontaneous haemorrhages occur without recognition of an evoking cause. Various bleeding-disposing factors are discussed, among others also influences of weather. For the investigation of the meteorotropic relations 1,802 episodes of haemorrhages in 223 haemophiliacs were coordinated to a complex scheme of weather phases. An undisturbed course of the weather was in general connected with a decrease of bleeding, whereas in an influence of low pressure with advection of cold air an increase of the haemorrhages was established. Conspicuous was furthermore the negative biotropism of the radiation-intensive sunny fine weather in summer, which is probably to be traced back to the thermic load in this weather situation. PMID- 2099024 TI - [Heparin-induced thrombocytopenia and thrombosis--a case report]. AB - The course of the disease of a 48-year-old female patient is described who in pre existing chronic myocarditis (and absolute atrial arrhythmia) during an attempt of rhythmisation with digitoxin and quinidine under protection of heparin developed a fatally ending thrombocytopenia and thrombosis and attention is paid to the necessity of the control of the coagulation status and the numbers of thrombocytes before and after every heparin therapy. The criteria according to Makhoul and Greenberg have a diagnostic value and they shall help in the early recognition of the heparin-induced thrombocytopenia and thrombosis and in the prevention of their full development. PMID- 2099023 TI - [Meteorologic effects on hemorrhagic diathesis in hemophilia. 2. Weather effects on hemophilia with special reference to the atmospheric temperature-humidity complex]. AB - The meteotropism of haemophilic haemorrhages was investigated for 1,802 episodes of bleeding in 223 patients with the help of selected parameters of the atmospheric temperature-humidity complex and the air pressure. The accumulation of haemorrhages under the influence of tropic air masses was particularly conspicuous. In low blood pressure the frequency of bleeding also increased, whereas high-pressure conditions showed a decrease of bleeding. The study clearly confirms that the haemorrhagic tendency in haemophilia is influenced by weather. Therefore a medico-meteorologic forecast should be taken into consideration for haemophiliacs. PMID- 2099025 TI - [Farmer's lung--a form of exogenous allergic alveolitis]. AB - Exogenic allergic alveolitides are caused by organic dusts which contain bacteria, moulds or vegetable and animal antigens. The farmer's lung as a form of the exogenic allergic alveolitis is a rare disease. The uncharacteristic symptomatology in the initial phase and in particular the retarded beginning of the symptom after several hours handicap the timely recognition in an early phase of the disease so that curative therapeutic measures are rarely possible. The cases of the disease are found only at the chronic stage, at the stage of the pulmonary fibrosis. Then the prognosis is unfavourable. In the Central Clinic for Heart and Lung Diseases Bad Berka 1,110 patients with alveolitides and lung fibroses were diagnosed in the period from 1975 to 1988. 306 of them could be clarified as exogenic allergic alveolitis, 61 of them (19.8%) were farmer's lungs. PMID- 2099026 TI - [Significance of skin changes in diabetes mellitus]. AB - 500 patients of a dispensaire of diabetes were inspected dermatologically. 335 patients had a duration of the glucose metabolism intoleration less than 10 years and 165 patients more than 10 years. 215 patients stated a striking family case history according diabetes. 54 per cent (273) of the cases showed an adiposity, 418 patients (83.6 percent) had pathological changes of the skin and mucosal changes. It is clear that dermatomycoses, eczema and pyodermias occur more often with acute metabolic disorder and adiposity. Neurovascular changes of the skin occur with long persistent glucose metabolism intoleration. Bad healing tendencles of wounds, pruritus, intensive dermatomycoses, balanitis, vulvitis, furunculosis and pyodermias are important references to a glucose metabolism intoleration. They should give rise to look for a diabetes irrespective of the age of the patient. PMID- 2099027 TI - [Computer-assisted diabetes therapy--a challenge for modern medicine]. AB - By the use of computers in the therapy of diabetes new diagnostic and therapeutic possibilities are brought about. The computers open the possibility for a comprehensive data seizing, evaluation of the stored material and possibilities of various abilities for demonstration. Moreover, it becomes possible to regulate the therapy more subtly with the help of self-adapting programs and in its consequence to render it more effective than the own management of therapy is able to do it. This manifests itself significantly in badly or only moderately stabilised diabetics. In very well educated and trained diabetics even the superiority of the management of the computer becomes visible. Here this can no more be shown in the improvement of the stabilisation of diabetes which can no more be improved without risks for the patient. In these patients it is the reduction of the frequency of hyperglycaemia, by means of which can be shown that the stabilisation of diabetes in diabetics who were well stabilised already before can still be improved by the computer therapy. In addition to this the computer seems to cause further positive effects on the learning behaviour of the diabetics. PMID- 2099028 TI - [Sonography of the retrobulbar space in autoimmune hyperthyroidism of the Basedow type]. AB - B-scan was performed to examine the orbits of 54 patients with Graves' disease. The thickness of the medial and lateral rectus muscle was measured and the results were compared to a control of 24 persons. 21 of the 54 patients with Graves' disease showed different degrees of eye changes in Graves' disease (Class I to IV). In comparison to the control 31 of the 33 patients without clinical signs or symptoms of Graves' orbitopathy have enlarged extraocular muscles. This guides to the presumption of an obligatory orbital involvement in Graves' disease. PMID- 2099029 TI - [Results of using EEG and carotid angiography for evaluating cerebrovascular insufficiency]. AB - In the cerebrovascular disease the EEG can give references at localisation, extension and course. The ability of statement is increased by methods of provocation and activation. On 35 patients with cerebrovascular insufficiency can be indicated that there are good correlations between changes on the large cerebral supply vessels and changes of the EEG, in particular in the carotid pressure trial. PMID- 2099030 TI - [Magnesium level in serum and erythrocytes in patients with chronic coronary heart disease without myocardial infarct]. AB - In 62 patients with chronic coronary heart disease without myocardial infarction the magnesium content of the serum and the erythrocytes was determined by means of the flame atom absorption spectrophotometry in comparison to patients with infarction and a group of healthy test persons. In the patients with chronic coronary heart disease without acute myocardial infarction the magnesium content of the serum was significantly reduced on the first day after the pectanginous attack. No decreased magnesium level of the erythrocytes was present on the first and tenth day after the pectanginous attack. PMID- 2099031 TI - [Catecholamine excretion in insulin-treated diabetic patients]. AB - The urine excretion of the catecholamines adrenalin, noradrenalin and dopamine as well as the serum levels of cortisol and STH were determined with the aim to establish objective criteria for a "latent" hypoglycaemia in diabetics. The altogether 45 insulin-requiring diabetics had no hypoglycaemia (n = 28) and the decrease of blood sugar, respectively, occurred during the daytime (n = 6) or at night (n = 11). From the results no significance for the catecholamines as parameters of a hypoglycaemia that happened long ago can be derived. Deviation in the circadian rhythms of the cortisol levels in diabetics with hypoglycaemias need the securing by further investigations. PMID- 2099032 TI - [Adult myeloneuropathic variant of adrenoleukodystrophy with Addison crisis]. AB - In a 32-year-old patient on account of an insufficiency of the adrenal cortex as well as of a leg-related tetraspasticity with a simultaneous subclinical peripheral neuropathy after exclusion of other endocrine and neurological diseases which are to be regarded differential-diagnostically the diagnosis of a myeloneuropathic adult variant of the adrenoleukodystrophy, the adrenomyeloneuropathy, was made. The disease in question is an x-chromosomally inherited disease, the basis of which is a metabolic disease in the destruction of long-chained fatty acids as basal disturbance. The cerebral radiologic exclusion diagnostics was made with CCT and MRT. On the basis of the literature the differential-diagnostic problems of this rare subspecies of the adrenoleukodystrophy which is at present causally not to be treated are discussed and it is referred to the clinical conclusions concerning a timely hormonal substitution therapy and genetic consultation. PMID- 2099033 TI - Therapeutic interventions in patients with CHD. A symposium. Strasburg, France, July 21, 1989. PMID- 2099035 TI - New mechanical devices for treatment of coronary artery disease. AB - Percutaneous high-speed coronary rotablation allows to remove arterio-sclerotic material from the vessel wall. A diamond-coated (15-30 microns) brass burr drill fastened to a flexible drive shaft rotating and tracking along a drill coaxial guide wire is used. The turbine rotates the drive shaft at 150,000-190,000 rpm. High-frequency rotational angioplasty was successful in 27 of 28 patients, but in about 34% additional PTCA was necessary. Only one patient went to bypass surgery, and myocardial infarction (CK less than 150 u/l) occurred in only one of 28 patients. No vessel perforation was observed. All vessels were open at 24 h control. The restenosis rate was not increased. The main indication for high speed rotational angioplasty seems to be rigid sclerotic lesions that cannot be passed by a conventional balloon catheter. Whether restenosis rate can be reduced by this method will be judged in future studies. In order to avoid acute complications of PTCA and to reduce restenosis rate, coronary stents were developed. Self-expandable and balloon-expandable stents are available. It could be demonstrated that these stents can be used as a bail-out system and can block elastic recoil of coronary arteries. The major remaining problem is that of subacute closure of coronary vessels. In order to prevent this, treatment with coumarine, acetylsalicylic acid, and dipyridamol is necessary. Coronary stents can be successfully delivered in more than 90% of the patients, as demonstrated by a cooperative study. In a highly selective patient group using single stents, restenosis rate measured 15%, but was higher in patients with multiple stents. PMID- 2099034 TI - Coronary dilation with nitrocompounds and calcium antagonists. AB - The vasodilatory effects of nitrocompounds and calcium antagonists on epicardial coronary arteries represent substantial antianginal mechanisms in the presence of coronary vasospasm or eccentric coronary stenoses. With high doses of nitrocompounds, angiographically normal coronary segments can be dilated by an average of approx. 30%, some coronary stenoses even by up to 100%, usually without severe reduction of blood pressure. With calcium antagonists, a similar extent of dilation of normal coronary arteries and eccentric stenoses can be obtained. Our own group demonstrated an average dilation of normal coronary arteries of about 20% after intravenous administration of dihydropyridine calcium antagonists; however, the average systolic blood pressure dropped below 100 mmHg after these compounds. Hence, although in isolated human coronary arteries high concentrations of calcium antagonists were shown to induce a considerably greater vasodilation than nitrocompounds, the early drop in blood pressure prohibits a higher dosage of calcium antagonists in vivo. In the presence of coronary artery disease, particularly when associated with coronary vasospasm, a combination of the two groups of compounds might be recommendable, since an addition of the effects of coronary vasomotor tone is likely. Furthermore, the antianginal effects of a reduction of preload and afterload are complementary. PMID- 2099037 TI - Anti-thrombotic drugs in the treatment of coronary heart disease: the present situation with aspirin. AB - The most important clinical studies of acetylsalicylic acid in coronary heart disease are compiled. In early 1970 trials unnecessarily high doses have been used. Since 1980 acetylsalicylic acid was given in a dose of about 1000 mg/day. Trials covering 10,000 patients were performed. Significantly decreased cardiovascular morbidity and mortality in patients with previous myocardial infarction was observed. Side effects were significant, haematemesis occurred in 0.1 per cent of patients per year. In secondary-prevention trials to treat unstable angina, which were performed in USA and Canada, the number of non-fatal myocardial infarctions was reduced by about 50 per cent. The dose applied was once 325 mg/day or four times the same dose. In patients after coronary artery by pass graft acetylsalicylic acid in a dose of 100 mg/day was clinically effective. The effectiveness of acetylsalicylic acid in secondary prevention is strongly supported by the ISIS-2 (Second international Study of Infarct Survival) trial reported in 1988. 17,000 patients were admitted to the trial. With respect to acetylsalicylic acid they received 160 mg/daily for 4 weeks. In addition the effect of streptokinase 1.5 mega-units i.v. was investigated in a cross over design against placebo. Acetylsalicylic acid in the low dose applied, significantly reduced non-fatal reinfarction. The effect of a combination with streptokinase was additive. Primary prevention trials: British and an American trial among volunteer doctors are not comparable because of differences in design and execution. No decrease in overall mortality rate was observed. Acetylsalicylic acid showed some effectiveness but the results are not conclusive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099036 TI - Thrombogenesis and inhibition of platelet aggregation. Experimental aspects and future approaches. AB - The pathophysiology of the acute coronary syndromes and of the progression of chronic coronary artery disease is complex, but in most cases it appears to be based on fixed atherosclerotic coronary disease with plaque rupture and superimposed thrombosis commonly followed by its organization by connective tissue. Furthermore, spontaneous or therapeutic reperfusion may be followed by re thrombosis, as it may occur in reocclusion post-thrombolysis, which is another pathologic event of significant clinical importance. The mechanisms of thrombus formation in atherosclerosis are not fully understood, but clearly involve local blood flow conditions, in addition to vascular and blood-borne factors that regulate cell-substrate and cell-cell interactions. The evolving understanding of the mechanisms of local flow and of cell-wall and cell-cell interaction is helping in the development of future approaches for the prevention and management of thrombotic events. PMID- 2099038 TI - Pathophysiological role of thromboxane A2 and pharmacological approaches to its inhibition. AB - The formation of the proischemic and prothrombotic thromboxane A2 (TXA2) and of its functional antagonist prostacyclin is increased in patients with unstable angina and myocardial infarction. Therefore, pharmacological interventions aim at an inhibition of the synthesis or action of TXA2 without interference with the desirable effects of prostacyclin. Clinical studies currently evaluate low-dose aspirin, thromboxane synthase inhibitors, TXA2/PGH2 receptor antagonists, and a combination of the latter two principles of action. The major advantages and disadvantages of these drugs are: 1. Aspirin irreversibly inhibits TXA2 and PGH2 synthesis in platelets, but also reduces the formation of the platelet-inhibiting PGD2 and prostacyclin--even under a low-dose regimen. 2. Thromboxane synthase inhibitors increase the formation of PGD2 and prostacyclin, but also enhance the accumulation of the potent platelet agonist PGH2. 3. Competitive TXA2/PGH2 receptor antagonists selectively inhibit the action of TXA2 and PGH2 and do not interfere with the eicosanoid metabolism, but their inhibitory effect can be overcome by very high local TXA2 or PGH2 concentrations. 4. Non-competitive TXA2/PGH2 receptor antagonists do not share this drawback. Therefore, they might combine the advantage of aspirin to exert an irreversible inhibition with the specificity of a TXA2/PGH2 receptor antagonist. However, these antagonists are in the stage of experimental studies. 5. The most potent of the clinically available principles of a platelet inhibition is the combination of a thromboxane synthase inhibitor with a competitive TXA2/PGH2 receptor antagonist. Agents that combine both principles of action in one compound are also under clinical investigation. PMID- 2099039 TI - Pathogenesis of restenosis. A correlation of clinical observations with cellular responses. AB - Angioplasty enlarges the lumen of atherosclerotic arteries, but also causes trauma and a response to injury in the form of fibrocellular intimal hyperplasia. Migration and growth of smooth muscle cells is a healing and repair process, filling the tissue gaps and molding a new lumen according to the local hemodynamic conditions. In addition to these reactive fibrocellular parts, tissue removed from restenosis sites also contains large amounts of old plaque components, as well as fresh thrombotic material, indicating that loose parts of the old vessel wall can contribute substantially to the restenosis by displacement as well as by their thrombogenicity. Excessive catheter trauma favors this reocclusion process by creating large dissections; however, insufficient dilatation does not leave enough space for the necessary fibrocellular healing. Current instrumentation cannot yet control the extent of the trauma well enough, and many proposed follow-up medical treatments aimed at preventing a variety of suspected restenosis mechanisms have not substantially improved the restenosis rate. So far, the most successful treatment of restenosis has been repeat angioplasty, often repeated several times, with excellent final results. PMID- 2099040 TI - Silent ischemia, its clinical importance as seen in 1989. AB - Silent myocardial ischemia is defined as spontaneous episodes of ischemic equivalents, especially transient ST-segment depression without being accompanied by typical anginal pain. Due to the improved recording possibilities of the T segment over 24 h, the phenomenon of silent ischemia was widely analyzed in recent years. The special methodological problems and, especially, newer clinical results (duration and daily number of episodes, circadian distribution of episodes) are extensively discussed; this also includes the correlation to coronary anatomy (extension of coronary artery disease) and to exercise testing. The prognostic aspects, and also the resulting therapeutic consequences and indications remain the objects of further studies; this is especially true for the indication for medical anti-ischemic treatment as analyzed by 24-h Holter monitoring. PMID- 2099041 TI - Familial hypercholesterolemia: dissection of a receptor disease. AB - In 1973, studies with cultured human fibroblasts by Brown, Goldstein, and colleagues showed that receptor-mediated endocytosis of low-density lipoprotein (LDL) is the regulatory principle in cellular cholesterol homeostasis. The complete sequence of metabolic events associated with the binding, uptake, and degradation of these cholesterol-rich lipoprotein particles by mammalian cells has been termed the LDL receptor pathway. This important process has two main tasks. First, it supplies cells with cholesterol, thereby mediating the removal of cholesterol-rich lipoproteins from the circulation. Second, it protects cells from over-accumulation of cholesterol, because the cholesterol derived from lysosomal hydrolysis of LDL cholesterylesters exerts a series of feedback control mechanisms designed to maintain a constant level of cholesterol within the cell. Thus, high extracellular concentrations of LDL reduce cellular synthesis of cholesterol (by suppression of the activities of 3 hydroxy-, 3-methyl-glutaryl CoA synthase and reductase, rate-limiting enzymes in cholesterol synthesis), stimulate its re-esterification, and decrease the number of LDL receptors, preventing further cellular entry of cholesterol. The suppression of LDL receptor activity by high plasma levels of LDL is beneficial for most cells, but the consequences caused by reduction of LDL receptor activity in the liver can be devastating. This is best documented in familial hypercholesterolemia (FH), in which defects in the LDL receptor gene disrupt the normal functions of the LDL receptor pathway. The clinical manifestation of the failure to remove LDL from the bloodstream at normal rates includes severe hypercholesterolemia and premature atherosclerosis. Some of the important findings that emerged from studies on structure/function relationships of the key player in the process, the LDL receptor itself, are described. PMID- 2099042 TI - Nitrate therapy in patients with coronary artery disease--preparations and doses with and without development of tolerance. AB - Rapid tolerance development with respect to hemodynamic, anti-anginal and anti ischemic effects is a relevant clinical problem associated with any longterm treatment with nitroglycerin, isosorbide dinitrate or isosorbide 5-mononitrate. Tolerance occurs with any dosing regimen that results in nitrate accumulation in the plasma or nearly-constant plasma concentrations, as is the case with multiple daily doses of oral nitrates or continuous application of transdermal patch systems. Nitrate tolerance can be prevented by the interval treatment. This encompasses incorporation of an application-free interval which prevents meaningful nitrate accumulation such that, from a low baseline level, renewed drug administration leads to an increase in the nitrate plasma concentration greater than 2.5-fold. From controlled studies, dosing regimens for interval treatment proven to be effective have been designated for isosorbide dinitrate and isosorbide 5-mononitrate, as well as for transdermal nitroglycerin patch systems. The early attenuation of nitroglycerin, seen within the first 12 h of its use, according to the results of a recently completed study, can be counteracted through continuously increasing plasma concentrations during this period. Interval treatment does not enable 24-h therapeutic protection. Studies with ST-Holter monitoring, however, have shown that adequate coverage can be provided for the period during which the vast majority of ischemic episodes occur. Clinically-relevant rebound phenomena do not occur during interval treatment. Pharmacological approaches to prevent nitrate tolerance, on the basis of the limited and, in part, conflicting data available, do not provide an alternative to interval treatment. PMID- 2099043 TI - Pulmonary arterial pressure and working capacity as parameters for checking the development of tolerance under nitrate therapy. AB - Testing of the chronic therapeutic effects of antianginal drugs is commonly performed by stress electrocardiography. It is well known that this type of testing is easy to be disturbed by the influence of circadian rhythmus and placebo. However, by hemodynamic measurements such as the determination of pulmonary arterial pressure each patient can serve as his own control in therapeutic studies if the reproducibility of these parameters is acceptable. In 29 patients with coronary heart disease the reproducibility of the following parameters was tested at rest and during exercise and found to be acceptable: heart rate, mean arterial pressure, mean pulmonary arterial pressure, and working capacity. In additional studies the application of these parameters on the control of chronic therapy with antianginal drugs was performed. The results were: 1. A 1-week placebo treatment does not influence the parameters. 2. Long term therapy with 3 x 20 mg of ISDN or IS-5-N daily over 4 weeks does not induce tolerance, whereas the dosage of 3 x 60 mg ISDN resp. 3 x 50 mg IS-5-N induces a remarkable degree of tolerance. 3. A 4-week therapy with 3 x 4 mg or 3 x 8 mg molsidomine daily resp. 4 mg or 8 mg molsidomine retard does not induce significant attenuation of the hemodynamic effects. 4. On a single-dose therapy with 50 mg IS-5-N retard ("interval-therapy") the therapeutic effects are maintained over at least 1 week. PMID- 2099044 TI - LDL-metabolism of the arterial wall--new implications for atherogenesis. AB - Increasing evidence arising from experimental work and epidemiological studies through the last few years shows an important role of LDL antioxidants in the pathogenesis of the early atherosclerotic lesions characterized by macrophagocytic foam cells. Also the maturation of the atherosclerotic lesion evolving from the fatty streak could be driven by pathological peroxidation of the LDL in the arterial wall. The search for new drugs against atherosclerosis should therefore include compounds that increase stability of LDL and reduce formation of cholesteryl ester formation in the foam cells via the scavenger receptor pathway. The aim of such a strategy is to keep LDL in the protective LDL receptor-mediated pathway of the liver, and to reduce LDL trapping by the arterial wall. PMID- 2099046 TI - Cardiology in Papua New Guinea in the twenty-first century. PMID- 2099045 TI - Heart failure--management in the 1990s. PMID- 2099047 TI - Clinical documentation of twenty cases of acute myocardial infarction in Papua New Guineans. AB - As predicted, coronary artery disease is being recognized with increasing frequency in the town hospitals in Papua New Guinea. This report contains the clinical characteristics of 20 patients with acute myocardial infarction admitted to the Port Moresby General Hospital. The clinical features of acute myocardial infarction were typical of the disease anywhere. The seemingly rare frequency of angina of effort in this group of patients is an interesting observation. The high in-hospital case fatality rate observed here is alarming. Urban dwelling, the male gender, smoking and diabetes were important risk factors in the development of this disease in these patients. PMID- 2099048 TI - Coronary artery surgery in an indigenous Papua New Guinean male. AB - The first case of coronary artery surgery in an indigenous Papua New Guinean male subject is described. A 42-year-old male with multiple risk factors developed two episodes of myocardial infarction. Coronary arteriography demonstrated severe obstructive disease in all three coronary arteries with moderate left ventricular dysfunction. Prognostic coronary revascularization was performed, with placement of four bypass grafts with six distal anastomoses. Recovery was largely uncomplicated. Maximal exercise test 6 months postoperatively showed normal exercise capacity with no evidence of ischaemia. He is pursuing an intensive program of risk factor management. PMID- 2099049 TI - Atrial fibrillation: the questions and controversies. AB - Atrial fibrillation is one of the commonest arrhythmias. It was first recognized over 100 years ago. However, many aspects including its mechanism, the role of autonomic as well as structural influences, and appropriate management including prevention of embolic events and indications for cardioversion have continued to provide questions for clinicians. This article is not intended to be all embracing but to deal with some of these more perplexing and controversial areas. PMID- 2099050 TI - Essential hypertension--investigations and management. AB - When one is faced with the problem of essential hypertension it is prudent to pay attention to lifestyle factors, especially alcohol, smoking and obesity. Modification of salt intake in the diet is a simple measure. Drug therapy will need to be long-term therapy and ease of treatment is important, which means that drugs given once a day or at most twice a day should be used. Diuretics and beta blockers are inexpensive and well proven but have many side-effects. Newer agents may have fewer side-effects but are more expensive. The choice will be an individual one. PMID- 2099051 TI - Clinical assessment of coronary disease. PMID- 2099052 TI - The use of sand-timers in the measurement of respiratory and pulse rates in children. PMID- 2099053 TI - Feeder arteries, longitudinal arterial trunks and arterial anastomoses of the lower human spinal cord. AB - 1. To study the arterial blood supply of the lower human spinal cord dye was injected into the thickest feeder artery and dinner diameters were measured of the arteries to and in the thoraco-lumbar spinal cord territory. 2. The arterial thoraco-lumbar territory consisted mainly of a ventral (A. spinalis anterior) and 2 dorsolateral longitudinal trunks (Aa. spinalis posterolaterales) linked by 2 sacral anastomoses. These longitudinal trunks were from the spinal cord segment T8 to the conus medullaris comparably thick and were fed to more than 80% by the 2 thickest radicular-medullary arteries. 3. The thickest feeder artery (Artery of Adamkiewicz, A. spinalis magna) had on average an inner diameter of 0.7 mm, contributed according to flow calculations 68% of the blood and fed from the left ventral side, mostly at T10 or L1 levels. The second thickest feeder had an inner diameter of 0.5 mm, supplied 18% of the necessary blood and fed mostly from the left dorsal side at the L1 level. The third thickest feeder with an inner diameter of 0.4 mm, contributed 7% from the left dorsal side. 4. Since the cruciate sacral anastomoses are in 20% of the cases thin or not present, the thickest ventral feeder artery and thickest dorsal feeder artery should be saved in operations in this region. Also the longitudinal arterial trunks should be saved to secure a sufficient blood supply of the cord. PMID- 2099054 TI - The value of some clinical and computer tomographic parameters in the prognosis of surgically treated patients with intracerebral hematoma. AB - The six-month follow-up of 83 surgically treated cases for intracerebral hematoma (ICH) was examined in relation to some clinical and computer-tomographic parameters (age, sex, accompanying diseases, clinical features, localization, ventricular involvement, time elapsed between stroke and surgery). Clinical and laboratory pre-requisites for admittance to the study were: 1) ICH with subcortical major component greater than 3 cm. in diameter, 2) a Glasgow Coma Scale (GCS) score at/or superior than 5, 3) any evidence of trauma, aneurysm, A-V malformation and tumor and 4) surgery not later than 96 hrs. after onset of bleeding. The role of the clinical picture and the ventricular involvement of ICH was strinkingly significant on both mortality as well as recovery rates while sex, some accompanying diseases and left localization influenced the recovery rate. Time elapsed between bleeding and surgery was not considered an objective parameter due to the variability of some organizatory and human factors. Age was an uninfluential factor. PMID- 2099055 TI - Two-dimensional ultrasonographic examination through postoperative defects in skull. AB - The authors describe the advantages of two-dimensional ultrasound examination in patient with skull defects of various origin. It is better to use ultrasound transducer with high frequencies, which have higher discerning capability to distinguish fine anatomic details. In comparison to CT the two-dimensional echoencephalography is harmless for the patient, it enables the monitoring of intracranial situation through an "acoustic window" and examination in several planes. PMID- 2099056 TI - [Malignant neurinoma of the suprascapular nerve]. AB - Malignant neurinomas are rare. The clinical symptoms are determined by the location of the tumor and are uncharacteristic. Therefore, the case of an 27-year old male patient is described who was operated on a malignant neurinoma of the suprascapular nerve. The treatment of choice is radical surgery. In addition, radiation and chemotherapy are indicated in some cases. PMID- 2099057 TI - Intraventricular hemorrhage due to rupture of arteriovenous malformations. AB - From 96 cases of intraventricular hemorrhage (IVH), 7 (7%) were due to rupture of arteriovenous malformation (AVM). 1 patient with a giant AVM had a primary IVH. Others had intracerebral hematoma (ICH) with rupture into the ventricular system. The severity of IVH (SIVH) correlated with neurological deficits on admission and with outcome of 6 (85%) patients and was considered as a reliable radiological prognostic indicator. 1 (14%) patient deceased and 4 (57%) survived with no or minor, 1 (14%) with moderate and 1 (14%) with major disability. Reviewing the literature, the conclusion is made, that in this relatively benign form of IVH, an active neurosurgical attitude regarding immediate evacuation of large ICHs and IVHs and if within reach AVMs is justified. PMID- 2099059 TI - [Intracerebral hematoma in post-traumatic dural arteriovenous malformation--case report]. AB - Posttraumatic dural arterio-venous malformations, as described in this case, are a rare incidence of head injury. Because of possible further complications, like spontaneous bleeding or a possible increase in size, the removal is advised. PMID- 2099058 TI - [Benign mesenchymal tumors of the spinal canal. Clinical aspects and long-term results]. AB - 22 patients were operated on because of a benign mesenchymal tumor in the spinal canal. 14 women and 8 men were affected, the average age being 37 years. Preoperatively 7 patients showed an incomplete or complete transverse lesion with a mean duration of the disease being 30 months. After the operation 19 patients showed an improvement, of these 17 were able to walk by themselves. 10 patients became again fit to work. One patient died after the operation. PMID- 2099060 TI - [Multilocular, ependymal cyst of the cerebellum]. AB - The present pathomorphologic report presents a case of an ependymal cyst of the cerebellum recurring 13 years after the first operative removal. The lesion is interpreted as ependymal cyst with growth-tendency. Pathogenesis and histogenesis of cysts of the present localisation are discussed. PMID- 2099061 TI - Benign osteoblastoma of vertebral column and skull. Report of two cases. AB - Osteoblastoma of the spine is a rare but important cause of back pain and the sciatica syndrome in young adults. Osteoblastoma of the skull is rare and the involvement of the orbital roof is very unusual. Clinical complaints and physical examination are not specific enough to provide a lead to the diagnosis. Bone scans and computerized tomography scans should be performed in all cases, to show the extent of vertebrae or calvarium infiltration by the tumor. To prevent recurrence and malignant transformation, the tumor should be completely removed whenever possible. If tumor excision is incomplete, a continuous follow-up is necessary to detect any recurrence or malignant transformation, which normally appears 5-10 years after the first operation (in one of our cases 7 years later). PMID- 2099062 TI - Multiple spinal meningiomas: case report and review of the literature. AB - A case of multiple spinal meningiomas, not associated with Recklingshausen's disease, is reported. It was a 73-year-old female, who presented with gait disturbance. All the available literature on this rare syndrome is reviewed. PMID- 2099063 TI - Association of suprasellar meningioma with pituitary adenoma. AB - An unusual case of an 81-year-old patient with coexisting pituitary adenoma and suprasellar meningioma is reported. The preoperative CT scan failed to demonstrate two separate masses. A short review of the literature is given. PMID- 2099064 TI - [On the discussion of the causes of the unusual seasonality (fall-winter) of viral hepatitis A]. PMID- 2099065 TI - [The electron microscopic study of bacterial development in colonies. The heteromorphous growth of bacteria during the natural development of a population]. AB - In this work data on the morphological features of the heteromorphous growth of bacteria in the process of the natural development of their population are presented. The authors believe that the heteromorphous growth of cells is inherent in the normal cycle of the development of bacteria in the population and that this process is reversible. It has certain regularities, common for different bacteria, in the variability of morphological manifestations and can be regarded as one of the stages of the natural L-transformation of bacteria. PMID- 2099066 TI - [The lytic activity of Yersinia pestis phage P 3d serovar]. AB - The lytic activity of plague phage II, serovar 3, with respect to 1,800 bacterial strains has been studied: 760 Yersinia pestis strains, 262 Y. pseudotuberculosis strains, 252 Y. enterocolitica strains, 166 Escherichia coli strains, 90 Shigella strains and 270 strains of other species. The phage has been found to lyse 81.8% of Y. pestis strains, 1 Y. pseudotuberculosis strain and 1 Y. enterocolitica strain. The representatives of other 19 bacterial species have proved to be resistant to the phage. Though having a wide range of action within Y. pestis, the phage does not lyse most of the strains of the causative agent of plague, isolated in certain natural foci. This fact offers promise for using the phage for the differentiation of Y. pestis. PMID- 2099068 TI - [The phospholipases of Proteus mirabilis]. AB - The method of screening Proteus for phospholipase activity has been worked out. The study of isolated clones of the same strain, used as an example, has revealed that clones differing in their phospholipase activity also differ in virulence and in some parameters of interaction in the host-parasite system. P. mirabilis phospholipases are supposed to be of importance as one of the factors contributing to the invasive properties of these microorganisms at the stage of overcoming the epithelial cell barrier of mucous membranes. PMID- 2099067 TI - [A polarographic method in assessing the cultural properties of the EV vaccinal strain]. AB - The kinetic and regulatory characteristics of the oxidation metabolism of glucose, whose differences in collection cultures correspond to their capacity for growth in fluid culture medium under the conditions of aeration and the periodic addition of glucose, have been proposed on the basis of the polarographic method used for the registration of microbial breath in vaccine strain EV. Pronounced metabolic disturbances resulting from the prolonged storage of the stock culture and working standards of strain EV lead to the deterioration of their working properties. PMID- 2099069 TI - [Infectious morbidity in the USSR: its structure, levels, dynamics and economic significance]. AB - Taking well-grounded strategic decisions on the control of infectious diseases requires the knowledge of modern epidemiological situation with respect to the total infectious pathology. The structure, levels and dynamics of morbidity in infectious diseases, registered according to Form No. 85 (Infection), on the territory of the USSR are considered. Besides, the evaluation of the economic damage inflicted to the national economy of the USSR by infectious morbidity is presented. PMID- 2099070 TI - [The status of immunoprophylaxis in the USSR and the means for its improvement]. PMID- 2099071 TI - [The determination of the optimal inoculation dose of an oral cholera chemical bivalent vaccine in a controlled experiment]. AB - 276 volunteers aged 19 years and over were placed under observation in the course of the trial of oral cholera vaccine in tablets, containing choleragen toxoid, O antigens of serovars Inaba and Ogawa and a number of Vibrio cholerae exoenzymes, for safety, reactogenic properties and immunological effectiveness. The vaccine was found to produce no reactions in a dose of 1-4 tablets; the administration of 3 tablets (300,000 binding units of the toxoid and 10,000 units of O-antigens, serovars Inaba and Ogawa) was shown to induce the most intensive synthesis of both antitoxins and vibriocidal antibodies in the blood sera of volunteers, as well as IgA coproantibodies. The oral vaccine was found to have an advantage over parenteral vaccines due to the absence of reactogenic properties and the formation of local immunity: coproantibodies appeared in 80% and 9% of the vaccinees respectively. PMID- 2099072 TI - [The effect of immune antibodies and the xanthine oxidase-xanthine enzymatic link on Vibrio cholerae]. AB - As revealed in experiments on V. cholerae, highly diluted cholera antiserum enhanced the inhibitory action of the enzymatic link xanthine oxidase-xanthine Fe2+ on the multiplication of V. cholerae, while low dilutions of the antiserum weakened this action. Normal rabbit serum produced no such effect. The antivibrionic effectiveness of the immune molecular cycle, viz. antiserum--the xanthine oxidase enzymatic link, was found to depend also on the concentration of xanthine. Immune antibodies to cholera antigens activated the bacteriostatic action of the enzymatic link at the concentration of xanthine oxidase equal to 0.0125 g/l and its bactericidal action at the concentration of xanthine oxidase equal to 0.025 g/l. In this article the values of the specificity indices of immune interaction and immunological effectiveness, characterizing the effectiveness of immune molecular cycles (antibodies--the xanthine oxidase enzymatic link), are presented. PMID- 2099073 TI - [The comparative characteristics of the immunomodulating properties of protein A from Staphylococcus aureus of different origins]. AB - The immunomodulating properties of highly purified staphylococcal protein A and its analog obtained by gene engineering techniques have been compared with those of commercial preparations. The comparison has shown that the differences observed in this investigation may be explained by the presence of admixtures of staphylococcal nature in commercial preparations. The preparations of highly purified staphylococcal and recombinant protein A stimulate humoral immune response and the processes of phagocytosis and do not show mitogenic activity with respect to T cells. The conclusion on the identity of the immunomodulating activity of the preparations of natural and recombinant protein A has been made. PMID- 2099074 TI - [An immunoenzyme test system for determining the staphylococcal exotoxin of toxic shock]. AB - A highly sensitive and specific enzyme immunoassay system for the determination of staphylococcal toxic shock exotoxin (TSE), permitting the detection of TSE at a concentration of 5-10 ng/ml, has been developed. The possibility of using this assay system for the selection of TSE-producing strains has been shown. 84% of staphylococcal strains under study have been found to produce TSE. PMID- 2099075 TI - [A comparative evaluation of the sensitivity of different methods for the serological diagnosis of leptospirosis]. AB - In this work the comparative evaluation of the sensitivity and serological specificity of the microcapsular agglutination (MCA) test, the passive hemagglutination (PHA) test and the microagglutination (MA) test are presented. In the MCA test leptospiral antigens, adsorbed on synthetic carrier capsules produced by Japan Lyophilization Laboratory, were used and the PHA test was made with the use of polyvalent erythrocyte diagnosticum. The study of blood serum samples from 46 leptospirosis patients revealed that the values of antibody titers in the PHA and MCA tests were 5.5-8.1 times higher than the traditional MA test. In the MCA and PHA tests antileptospiral antibodies could be detected as early as on days 1-3 of the disease when the results of the MA test were negative or very low. The maximum values of antibody titers in the MCA and PHA tests were detected on days 11-15 of the disease and in the MA test, on days 21-25. The MCA and PHA tests are genus-specific and permit the detection of antileptospiral antibodies irrespective of the serogroup of the infective agent. In the study of the blood sera of 40 patients with diseases of nonleptospiral etiology the MCA and MA tests yielded false positive results in 7.5% and the PHA test, in 12.5% of cases in titers below the diagnostic level. These data are indicative of high sensitivity and specificity of the serological tests used in this study. PMID- 2099076 TI - [The use of the macrophage disappearance reaction for detecting delayed hypersensitivity to Yersinia pestis antigens]. AB - The possibility of using the reaction of macrophage disappearance (RMD) for the detection of delayed hypersensitivity (DH) to Y. pestis has been studied. As the result of these studies, RMD has been found suitable, in principle, for use in the quantitative evaluation of DH to Y. pestis. High sensitivity and specificity of this reaction have been established. The presence of DH in the process of the formation of immunity after immunization with Y. pestis antigen FIA has been shown. RMD can be observed during 28 days after immunization (the term of observation). PMID- 2099077 TI - [The determination of allergen-specific IgE and IgG antibodies in patients sensitized to the house dust mite Dermatophagoides pteronyssinus]. AB - 45 patients, hypersensitive to house-dust mites, were examined by the method of skin tests to D. pteronyssinus allergen. Besides, in their blood sera the levels of allergen-specific IgE antibodies were determined in the radioallergosorbent test and allergen-specific IgG antibodies, in the enzyme immunoassay. These tests revealed that in 91% of the patients the results of skin tests were positive, in 68% an elevated level of specific IgE antibodies and in 93% of the patients an elevated level of specific IgG antibodies were detected. All patients showed the positive result in one of the above-mentioned tests. The largest group of the patients (55%) included persons showing the positive result of the skin test and having elevated levels of allergen-specific IgG and IgE antibodies. Thus, in cases of hypersensitivity to house-dust mites the levels of allergen-specific IgG and IgE antibodies in the patients' blood sera should be determined. PMID- 2099078 TI - [Infectology--new approaches to the planning and evaluation of scientific topics. The socioeconomic importance of planned scientific research]. PMID- 2099079 TI - [The role of macrophages in the immunogenesis of plague]. PMID- 2099081 TI - Association between chemiluminescence stimulating and IL-2 inducing activities of Staphylococcus aureus strains in human and mouse mononuclear cells. AB - The plastic adherent fraction of human mononuclear cells (MNC) responded with maximal chemiluminescence (CL) upon stimulation with greater than or equal to 1000 bacteria per cell of heat killed preparations of Staphylococcus aureus strains. Different strains had different CL stimulating activities and their sequences were similar on MNC from different blood donors. IL-2 inducing and CL stimulating activities seem to be parallel features of S. aureus strains, since their sequence set ups established on the basis of these two properties were almost identical. The same phenomenon could also be observed in a mouse system, in which activated peritoneal cells (PC) were the most active CL exhibiting population. The IL-2 inducing activity of staphylococci in mouse spleen cells and their CL stimulating activity in activated PC followed a similar pattern too. The sequences of CL inducing activities of different staphylococcal strains were in good agreement in human and mouse cells. Representative strains with high, moderate and low CL inducing activities followed the same sequence of virulence for mice. PMID- 2099080 TI - Immunotoxicity testing of mycotoxins T-2 and patulin on Balb/c mice. AB - The effects of patulin and T-2 toxin were investigated on immunological responses of Balb/c mice. In vitro patulin had a stimulatory effect on splenocytes at lower concentration (1 nM to 10 nM) and strongly inhibited lymphocyte proliferation at higher concentrations (ID50 from 0.02 to 0.24 microM depending on mitogens). In the same experiments T-2 toxin was 100-fold more potent (ID50 from 0.7 to 2 nM). In vivo studies on immunity were performed in mice receiving Bordetella pertussis antigens and keyhole limpet haemocyanin. Patulin significantly reduced delayed type hypersensitivity to B. pertussis antigen and did not reduce anti-KLH antibody production. T-2 toxin had no effect on delayed type hypersensitivity and reduced anti-KLH antibody production. Splenocytes were harvested in mice with or without antigen stimulation to assess mitogenic responses. Patulin generally increased splenocyte proliferation, therefore T-2 toxin effect depended on the immunological status of mice and on the dose injected. At the lower doses (0.8 mg/kg), T-2 toxin enhanced responses to mitogen, but at the greater dose (1.6 mg/kg) T-2 toxin enhanced responses to mitogen of antigen stimulated mice and decreased responses of unstimulated mice. PMID- 2099082 TI - Potential Shigella flexneri 2a and Shigella sonnei I live vaccinal strains. Characterization of immunogenicity in animal models. AB - Rats and rabbits were immunized intraintestinally with different doses of virulent and nonvirulent live Shigella flexneri 2a and Shigella sonnei I strains. The nonvirulent strains had one or two attenuating markers. The period of excretion with the faeces of the bacteria and of their polysaccharide antigens, the proliferation of antigen-binding and antibody-producing cells in the spleens and gut-associated lymphoid tissues and the levels of antibodies in sera and faeces were studied. Attenuated strains S. flexneri 2a 77 and S. sonnei I 3359 induced the most potent and long lasting local immune response. PMID- 2099083 TI - Plasmid analysis of clinical isolates of Bacteroides fragilis group strains. AB - Cryptic plasmids were isolated from 26 of 52 Bacteroides fragilis group strains derived from severe infections. Four strains harboured two plasmids, one three plasmids and one five plasmids with different molecular weights. The same molecular weight plasmid (3.7 Md) was isolated from 17 of the 26 plasmid containing B. fragilis group strains. No correlation was found between plasmid harbouring and resistance against ten antibiotics and different heavy metal ions. No curing of the strains from the plasmids was achieved with ethidium bromide and acridine orange. PMID- 2099084 TI - Size-dependent regeneration of Gibberella protoplasts. AB - Regeneration ratios of protoplasts formed from the plant pathogenic gibberella fujikuroi with a mixture of lytic enzymes were studied. The heterogeneous population of protoplasts was separated into groups differing in regeneration ratio. The frequency of regeneration was higher for large protoplasts containing an increased number of nuclei. PMID- 2099085 TI - Bacteriological proficiency testing in Hungarian clinical microbiology laboratories. AB - In course of a proficiency testing programme carried out in 1989, a total of 47 clinical microbiology laboratories of public health stations and of hospitals received freeze-dried cultures for isolation, identification and antimicrobial susceptibility testing. The specimens contained bacteria that occur in everyday work, including those that require improved methods of cultivation and identification. Nine public health laboratories and one hospital laboratory achieved excellent results. Good results were attained by 11 public health and 6 hospital laboratories. Four public health and 10 hospital laboratories were on the medium level and 4 hospital laboratories did not reach even this degree. The main failures were due to an insufficient anaerobic cultivation, unreliable identification and negligation of controls for drug susceptibility tests. PMID- 2099086 TI - [The biotransformation of cui xing ning in the isolated perfused rat liver]. AB - Similar to eserine, Cui Xing Ning [CXN),5-(1,3,3-trimethylindoline) N, N-dimethyl carbamate] is a choline esterase (ChE) inhibitor. The biotransformation of CXN, which had been studied in vivo and in vitro unsuccessfully, was studied by using isolated perfused rat liver (IPL) method. Six metabolites of CXN from the perfusate were separated by HPLC, and identified with MS, 1HNMR or compared with the authentic compounds. Metabolite I is unchanged CXN, the other are oxidized metabolites. Most of the metabolites lost their activities of ChE inhibition strikingly except metabolite III which retained the 2-position unchanged. The toxicities of some metabolites (II,V) decreased obviously. PMID- 2099088 TI - [Synthesis and analgesic activity of the derivatives of 3-methyl fentanyl]. AB - Six analogues of 1-substituted-3-methylfentanyl were synthesized. All of them are liquid compounds. Preliminary pharmacological results showed that some compounds of 1-beta-substituted vinylethyl-3-methyl derivatives of fentanyl have strong analgesic activity with typical morphine-like action. PMID- 2099087 TI - [Protective effect of 2-[p-(dimethylamino) styryl] pyridine methiodide (DSPM) on acute experimental myocardial ischemia]. AB - ip DSPM 5 mg/kg 1 or 4 h before excision of the heart was found to prevent damage to the heart due to global myocardial ischemia. Compared with the controls, the heart rate, coronary resistance, contractile force and edema of the heart were all greatly improved during the 60 min reflow after 25 min of no-flow, especially the heart pretreated with DSPM 4 h prior to excision. In addition, DSPM 1.5, 6 mg/kg markedly reduced the myocardial Ca2+ content measured by isoproterenol in mice. DSPM at higher dosage also lowered the normal myocardial Ca2+ content. These results suggest that DSPM may have a protective effect on myocardial ischemia which might be associated with its calcium antagonistic action. PMID- 2099090 TI - [Studies on the chemical constituents of Rhododendron molle G. Don]. AB - Two physiologically active diterpenoids were isolated from the flower of Chinese azalea (Ericaceae Rhododendron molle G. Don). One of them is a new compound, named rhodomollein-III; its structure has been established as 1 through IR, MS, 1HNMR, 13C NMR, 1H-1H COSY, 1H-1H NOESY, 13C-1H COSY and long-range 13C-1HCOSY. The other one is the known rhodojaponin-III. PMID- 2099089 TI - [Antianaphylactic components of Asarum forbsii Maxin]. AB - From the ethyl acetate extract of Asarum forbesii Maxin, four new constituents, asarumin A(I), B(II), C(III) and D(IV), were isolated along with elemicin (V), trans-asarone(VI) and linoleic acid(VII). The structures of the new compounds were elucidated as methyl 3 S-benzoyloxy-2 S-hydroxy-2-isopropylbutyrate for I, methyl 2 R-benzoyloxyisopentanoate for II, methyl 2 R-trans cinnamoyloxyisopentanoate for III and methyl 2 R-piperonyloyloxyisopentanoate for IV. Compounds I, II, III and VII showed weak inhibition of PCA in rats, but the other compounds were inactive. PMID- 2099091 TI - [Studies on antibacterial constituents from the roots of Rubia cordifolia L]. AB - Twelve compounds were isolated from the roots of Rubia cordifolia L.. Nine of them were established by chemical and spectroscopic methods to be alizarin (I),1 hydroxy-2-methyl-9,10-anthraquinone(II),1,3,6-trihydroxy-2-methyl- 9,10-anthra quinone-3-O-(6'-O-acetyl)-alpha-L-rhamnosyl(1--- -2)-beta-D- glucoside(III),1,3,6 trihydroxy-2-methyl-9,10-anthraqueinone-3-O-a lpha- L-rhamnosyl(1----2)-beta-D glucoside(IV),1,3,6-trihydrozy-2- methyl-9,10- anthraquinone-3-O-(6'-O-acetyl) beta-D-glucoside(V),2-carbomethyoxy++ +-3-prenyl- 1,4-naphthohydroquinone di-beta D-glucoside(VI),rubimallin(VII),beta- sitosterol(VIII) and daucosterol(IX), among them, V is a nwe compound and IX was obtained from this genus for the first time, III, VI and VII showed certain antibacterial activities. PMID- 2099092 TI - [HPLC analysis of flavonoids in the root of six Glycyrrhiza species]. AB - Ten flavonoids isolated from six species of Glycyrrhiza root were analysed by reversed phase HPLC. A column packed with Partisil 5 ODS-3 and gradient elution by using different percentage of methanol (B) in water-glacial acetic acid (97:3 V/V) (A) were used to separate licochalcone A, isoschaftoside, schaftoside, liquiritin, isoviolanthin, violanthin, ononin, isoliquiritin, 4', 7 dihydroxyflavone and licoflavone A. Nine Glycyrrhiza samples of six species were analysed to determine their composition and content of the flavonoids. The results showed that the composition and content of the flavonoids of different Glycyrrhiza species were different as well as the same species but collected in different places. PMID- 2099093 TI - [Determination of ephedrine, pseudoephedrine and strychnine in jiufen san by HPLC]. AB - An HPLC method was established to separate and determine ephedrine (I), pseudoephedrine (II) and strychnine (III) in Chinese traditional medicine, Jiufen San, on a mu-Bondapak C18 column (10 microns, 3.9 mm x 30 cm) by using 0.01 mol/L KH2PO4-methanol as mobile phase. The programmed gradient elution was carried out and recoveries were determined as 98.94 +/- 2.2% for I, 97.37 +/- 1.9% for II and 100.7 +/- 1.9% for III respectively. An extracting and pretreatment method was designed and the result showed that the extracting efficiency of this method was 1.33 times (I) and 1.29 times (II) higher than those of the Chinese Pharmacopoeia method. PMID- 2099094 TI - [Hydrophobic modification of water soluble drug and its reconstitutable liposomes]. AB - Water soluble drugs carried in liposomes have rather low encapsulation percentage (EP%) and poor stability. In this paper metronidazole (I) was chosen as a model of water soluble drugs which was modified by means of esterification. Its myristic ester (II) was synthesized. On studying the liposomes of I and II, the results have shown that EP% and stability of II were more than ten times as high as that of I. Furthermore, the reconstitutable liposomes of II were prepared successfully. The amoebacide activity of II liposomes was increased also. Therefore, the hydrophobic modification of water soluble drugs is a good way to improve the drug entrapped in liposomes. PMID- 2099095 TI - [Effects of isocorydine on contraction of the rabbit oviduct smooth muscle]. AB - On isolated isthmus of oviduct of the rabbit, Isocorydine (Isoc) (3 mu mol/L) decreased significantly the frequency of spontaneous contraction and muscle tension, but not the amplitude of contraction. The tension and frequency of spontaneous contraction can be suppressed by Isoc at concentrations from 3 to 300 mumol/L. The amplitude of contraction was decreased only at 300 mu mol/L. It is suggested that the frequency and tension of spontaneous contraction of isthmic muscle are more sensitive to Isoc than the amplitude. Isoc antagonized the norepinephrine-induced contraction of the oviduct. The transport of ova through the oviduct reduced by hCG could be delayed by Isoc. PMID- 2099096 TI - [A new lignanolide from the leaves of Daphne genkwa]. AB - A new (-)-4-oxo-2,6-bis-(3',4'-methylenedioxy phenyl)-3, 7-dioxabicyclo[3, 3, 0] octane lignan, genkdaphin was isolated from the leaves of Daphne genkwa Sieb. et Zucc. mp 118-119.5 degrees C, C20H16O7 (HRMS, 368.08631, M+), [alpha]27D-64.8 degrees (c 0.5, CHCl3). On the basis of UV, IR, MS, 1H and 13CNMR spectral analysis, the structure of the genkdaphin has been established as (-)-4 oxosesamin. PMID- 2099097 TI - [High resolution gas chromatography and its application in pharmaceutical analysis]. PMID- 2099098 TI - Myelinoclastic diffuse sclerosis: a case report. AB - The clinical features and pathological findings of a patient with myelinoclastic diffuse sclerosis, corresponding to those described by Schilder in 1912, are reported. The course of the disease, having lasted for ten years, was interrupted by periods of partial remissions. Peripheral nerve involvement was also found. PMID- 2099099 TI - Hepatic lesions in Syrian golden hamsters with pancreatic carcinoma induced by N nitrosobis(2-oxopropyl)amine (BOP). AB - Hepatic lesions in 25 male and 24 female Syrian golden hamsters with N Nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic cancer have been studied. Although BOP produced pancreatic cancer in 100% of the animals, its hepatocarcinogenic potential proved to be very weak, only occasional preneoplastic foci, neoplastic nodules and hepatocellular carcinoma developed. However, a broad spectrum of mainly proliferative, non-neoplastic alterations were found in the liver. The major site of alterations was the portal space, especially the biliary ducts were affected: bile duct hyperplasia, oval cell proliferation and formation of biliary cysts were the most frequently encountered changes. In the large ducts of the female hamsters a goblet cell metaplasia occurred, but the male animals were devoid of this lesion. Our results demonstrate that although the BOP is considered as a selective pancreatotropic nitrosamine derivate, it may cause various proliferative changes in the biliary duct system of hamsters. PMID- 2099100 TI - Pathological confirmation of foetal cystic fibrosis following prenatal diagnosis. AB - Here we report on the results of histopathological analysis of several organs of 5 foetuses and 2 newborn infants with cystic fibrosis. They were examined with HE, PAS, AB, HID and "Stains-all" techniques on paraffin sections. We concluded that there were significant differences in the epithelial mucin composition of several organs of the effected foetuses compared to 6 controls as early as the 17th week of gestation. An increase in the amount of neutral and acidic mucins was observed in the acini of the pancreas, bronchi and the mucosa of the gastrointestinal tract accompanied with a well defined decrease of sialic acid rich components of pharyngeal submucosal glands. PMID- 2099101 TI - Lectin histochemical characterization of the mouse, rat and human lymphoid tissues. AB - The authors performed a comparative lectin histochemical study on lymphoid organs of three species with 12 different lectins. The T and B cell regions and the accessory cells of lymphoid tissues were studied. The species differences show that the BALB/c mouse can be a valuable tool in modelling human lymphoid tissues, whereas Wistar rats exhibit great differences in lectin binding patterns as compared with human tissues. The positivity of peanut agglutinin binding of cortical and the negativity of medullar thymocytes in mice can be regarded as an indicator of cell differentiation. The focal distribution of peanut agglutinin positivity in the centrocytic region of human and rat germinal centres marks a small B cell subpopulation at the early stage of differentiation, while Bandeira simplicifolia binding is characteristic of a broader B cell lineage, but only in rats and mice. Canavalia ensiformis lectin seems to be a reliable marker of accessory cells (dendritic and interdigitating reticulum cells as well as macrophages) in all species studied. PMID- 2099102 TI - Digital image analysis of variations in the origin of the deep femoral artery in human foetuses. AB - Examination of vessels' radiograms with the use of microcomputer digital image analysis was adopted to the femoral artery in human foetuses. The system makes it possible to shorten the investigation time as compared with conventional methods and to obtain objective results. Investigations were performed on 100 human foetuses (72 males and 28 females) aged 4th to 8th month. The configuration in the radiograms of the deep femoral artery showed four main origination types. PMID- 2099103 TI - [Glucagon secretion in patients with nephrotic syndrome in primary glomerulonephritis during the period of renal efficiency]. AB - The performed studies covered 28 patients with nephrotic syndrome and 10 healthy individuals. The oral glucose tolerance test in 20 patients with nephrotic syndrome revealed glycemic values within the norm, and features of defective tolerance to glucose or diabetes in 8 subjects. Hyperglucagonemia was recorded in all the patients with increased glycemic values in the oral glucose tolerance test. It was found that hyperglucagonemia appeared in 70% of studied patients with normal glucose tolerance. All the groups of patients with nephrotic syndrome disclosed a decrease in glucagonemia, observed in normal subjects, in the course of oral glucose tolerance test as well as slower disappearance of glucagon from the circulatory system, which may be of certain significance in the occurrence of hyperglucagonemia. It has been ascertained that hyperglucagonemia may be one of the factors having influence upon a higher incidence rate of glucose tolerance abnormalities than in general population; can have a share in intensified catabolic processes, and also counteracts the effects of increased tissue absorption of glucose in patients with nephrotic syndrome. There has been a lower stimulating action of exogenic glucagon on insulin secretion in patients with nephrotic syndrome and hyperglucagonemia as compared to patients with normoglucagonemia and to healthy subjects. PMID- 2099104 TI - [Serum thyroxine and triiodothyronine levels after a single dose and after 2 month-long thiamazole treatment of Graves' disease with reference to drug's pharmacokinetics]. AB - The performed studies covered 48 subjects, inhabiting the Western Pomerania, therein 40 patients with hyperthyroidism in the course of Graves-Basedow's disease (32 females and 8 males, aged 21-64 years) as well as 8 healthy individuals (5 females and 3 males, aged 23-36 years, with negative anamnesis towards thyroid diseases), who made up the control group at determining the pharmacokinetic parameters after a single oral dose containing 60 mg of thiamazole. On the basis of estimating the time of treatment with "full dose" of thiamazole, indispensable for attaining clinical euthyreosis, according to criteria provided by Crooks et al., the patients with hyperthyroidism during Graves-Basedow's disease were divided into 2 subgroups: 1). Subgroup IA included 22 patients, in whom the clinical state of euthryreosis was obtained in 28 days of therapy with "full dose" of thiamazole. 2). Subgroup IB encompassed 18 patients, in whom euthyreosis appeared after at least 35-day-long treatment with a "full dose" of thiamazole. The differing behavior of thyroid hormones and thiamazole pharmacokinetics+ in both subgroups of patients has furnished the basis for the following conclusions to be drawn: The patients with hyperthyroidism in the course of Graves-Basedow's disease, attaining rapidly the clinical euthyreosis during the treatment with "full dose" of thiamazole, are found to normalize the concentrations of thyroxine and triiodothyronine in serum after shorter time than it is done by patients requiring a longer drug application in a "full dose". In patients achieving euthyreosis both after short and long time of treatment with "full dose" of thiamazole, the normalization in concentrations of thyroid hormones in serum markedly exceeds, by about 2-4 weeks, the establishing of clinical euthyreosis. In patients, who readily attain the clinical euthyreosis, the concentrations of thiamazole in serum, after a single "full dose" as well as during two-month-long treatment, are significantly higher than in patients reaching euthyreosis slowly, in spite of the fact that there were no outstanding differences in absorbing the drug from the alimentary duct in both subgroups being compared. The cause that the clinical effect varies in the compared subgroups of patients with hyperthyroidism during the Graves-Basedow's disease is the difference in thiamazole metabolism in the organism, most likely in the liver. PMID- 2099105 TI - [Clinical, histopathological and bacteriological evaluation of the sequelae of premature rupture of fetal membranes in parturients after cesarean section]. AB - Studies were performed on 83 women, who delivered by cesarean section, as well as on their 84 infants (one bigeminal pregnancy). Five study groups were isolated, namely: I-22 delivering with prematurely ruptured fetal membranes (PRFM) greater than 12 h, II-36 delivering with PFM 12 h. III-58 total of delivering with PRFM, IV--with PRFM + PFM (preserved fetal membranes)--25 delivering (control group), and V - 83 delivering with PRFM + PFM. The evaluation covered clinical data taken from obstetrical history of the delivering woman, course of pregnancy, operation and post-operative period. Histological examinations included the specimens from the uterine muscle, 3 umbilical cord specimens, those of ++extra-placental fetal membrane, as well as placental sections. The inflammatory changes in the studied tissues were classified into: profuse inflammatory infiltrations (+), inflammatory infiltration of minor degree (+/-), and absence of inflammatory infiltration (-). Bacteriological examinations involved smears from vagina and from cervical canal of uterus prior to operation, amniotic fluid taken in the course of operation, as well as pharyngeal smears and gastric content of the newborn infant. It has been shown that in the group of bearing women, in whom the time from PRFM to delivery was longer than 12 hours more harmful consequences were observed than in the group of bearing women, in whom this period was shorter than 12 hours, and that the length of the period itself from PRFM moment to the delivery does not exert any influence on the increase in the rate of infections in the bearing mothers. It has been ascertained that immediate consequence of PRFM for the mother is the rise in the incidence rate of amniotic fluid infection, while the consequence in respect of the newborn infant is an increased incidence rate for children being born with poorer general conditions in cases with preserved fetal membranes at the time of delivery, and also that whenever the period from PRFM to delivery is longer than 12 hours there is great likelihood that inflammatory infiltrations may appear in the uterine muscle of the bearing women, examined frequently "per vaginam" at the time preceding the parturition and during the latter's course.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2099106 TI - [Retrospective analysis of patients with multiple myeloma; clinical characteristics and prognostic factors]. AB - The performed clinical analysis covered 80 patients with multiple myeloma, treated at Hematological Clinic of PMA in the years from 1974 to 1984. The following prognostic factors were analyzed: age, sex, living place, clinical advancement period of the disease, functional state according to Karnofsky (Karnofsky's index), monoclonal protein type, the concentration of urea, creatinine, calcium in blood serum, hemoglobin concentration as well as the neoplastic tumour mass. These factors were considered to indicate poor prognosis: severe anemia, hypercalcemia, renal failure, and Karnofsky's index being below 70 points. PMID- 2099107 TI - [Evaluation of hygiene indices in studying the relations between oral hygiene and periodontitis based on epidemiologic studies]. AB - The aim of the studies has been to determine the diagnostic clinical value of selected indices and to demonstrate their specific applicability under definite conditions. The study covered 184 subjects in two age groups: young persons aged 15-20 years, and adults being 20-45 years old. The oral hygiene was estimated by the following indices: OHI-S (Oral Hygiene Index-Simplified), Pl. I. (Plaque Index). C.P.I. (Cervical Plaque Index). The ++periodontium state was assessed by using the gingival index (G.I.). Periodontal index was defined by gingival index (G.I.), Russell's periodontal index (P.I.), as well as Kotzschke's periodontal index (K.I.). Sulcus fluid rate (S.F.R.) was also examined by Brill's method. The comparison of numerical values of the indices and statistical analysis of their cross correlation have shown that all of the indices having been involved in the study are of similar diagnostic value. However, C.P.I. appeared to be the best one, since the periodontitis indices most readily reacted to changes of its value. On the other hand, the oral hygiene index (O.H.I.-S) correlated more closely with inflammatory indices in adults, which suggests its particular applicability for examinations in this age group. (Pl. I.) may be used in young persons, in whom there are still no mineralized deposits of tartar. This index is easily determined, thus providing the possibility to evaluate the oral hygiene in quite a short time. Due to the fact that the quantitative measurements of sulcus fluid rate failed to reveal any statistically significant relation between the level of the sulcus fluid and periodontitis as well as oral hygiene in the youth, it has been ascertained that the sulcus rate measurement is of limited usefulness for clinically evaluating the state of parodontium, and may be resorted to in adult individuals only. It has also been disclosed that the resistance of parodontium to the action of pathogenic factors is greater in younger subjects. PMID- 2099108 TI - [Fluoride level in human nails and its significance]. AB - Bone tissue investigation provides the best indicator for fluorine saturation of the organism. However, the intravital bone biopsy--as an invasive method, is not applicable in prophylactic studies. Thus, attention was focussed on the nails that constitute an easily accessible material being able to reflect the chronic accumulation of fluorine in the organism. In the actual paper it has been endeavoured to find out the routes, on which fluorine is deposited in the nails, if there is any dependence between the fluorine content in the nails and the age of the studied subjects, and whether the concentration of fluoride in the nails depends on the fluctuation of this element in the environment, and which of the parameters exert influence upon it. The performed investigations permitted the following conclusions to be drawn: 1. The nails furnish a readily accessible material for studying fluorine saturation in the organism. 2. Fluorine may be accumulated in the nails on internal pathway through circulatory system, and from outside--by means of direct absorption. 3. Since relatively high content of fluoride has been revealed in the nails of the youngest children, they should be protected against further supply of fluorine compounds from outside. 4. In the areas not polluted by fluorine compounds there is a lack of statistically significant dependence between the content of fluoride in the nails and the age. PMID- 2099109 TI - [Immunologic reactivity of the skin in chronic hepatitis]. AB - The aim of the study was to evaluate the practical usefulness of immunological examination of the skin in chronic liver diseases, especially chronic active hepatitis (CAH) HBsAg (+). Fifty-four patients were examined. DNCB and tuberculin skin tests as well as direct immunofluorescence method for clinically normal skin specimens were used to estimate some of the immunological processes in the skin. Results of immunopathological examinations of the skin in a group of patients with CAH HBsAg (+) were compared with some clinical, biochemical and serological data. The skin delayed hypersensitivity tests with DNCB and tuberculin were negative in the majority of persons having CAH HBsAg (+), which provided support for the cellular immunity discrimination in these cases. It was demonstrated that serum HBsAg titer in patients with CAH HBsAg (+) and positive tuberculin test was significantly lower as compared to the group with negative tuberculin test. Deposits of immunoglobulins, particularly IgM, and C3-component of complement in vessel walls were stated in clinically normal skin in patients with CAH HBsAg (+) and other liver diseases. They were found in about 3/4 of the examined cases of CAH HBsAg (+). C3-deposits were recorded significantly more frequently in superficial skin vessel walls in patients with histologically diagnosed liver cirrhosis. It seems that homogenous deposits of IgM or C3 in skin vessel walls may indicate early and granular--later stage of CAH HBsAg (+). Immunological examinations of the skin may be useful for better evaluating the cases of chronic liver diseases, particularly in chronic active hepatitis with HBs-antigenaemia. PMID- 2099110 TI - [Use of ultrasonography in the diagnosis and monitoring of the treatment of congenital hip dysplasia in infants]. AB - On the basis of 1892 ultrasonographic examinations of 1582 hip joints in 633 girls and 158 boys aged from 10 days to 12 months, the author presents the method and its significance for objective of diagnosis, prevention, and treatment of the congenital dysplasia of the hip. He performed the examinations and evaluated the sonograms using the method provided by Graf. The most significant clinical symptoms of dysplasia of the hip are the increased antetorsion of femoral neck, as well as the Ortolani and Barlow symptom. However, in spite of their presence in 58 cases, the ultrasonographic image has not shown any abnormal development of the joint. At the same time, the author has disclosed the occurrence of a minimal percentage of dysplasia (7%), with no noticeable symptoms detected by the clinical examination. At present, the suspicion of hip joint dysplasia based on the clinical examination, should be confirmed by ultrasonography before starting the treatment, in order to avoid the harmful consequence arising from the therapy of the normally formed joints. The performed examinations have proven that ultrasonographic representation of hip joints is the most precise and objective diagnostic method. Its employment in the first days of the newborns' lives is of great significance for congenital dysplasia prevention. PMID- 2099111 TI - [Islet cell cytoplasmic antibodies (ICA) and complement-fixing islet cell cytoplasmic antibodies (CF-ICA) in patients with newly detected type 1 diabetes mellitus of short duration]. AB - Cytoplasmic islet cell antibodies and endogenous insulin secretion were studied in 60 children and adolescents having insulindependent (Type I) diabetes mellitus. The age of the subjects was 2-34 years. Thirty-nine patients were investigated at the time of diagnosis, in the group of 21 patients duration of disease was shorter than 2 years. Islet cell antibodies were analysed by indirect immunofluorescence for both conventional (ICA) and complement-fixing (CF-ICA) antibodies using cryostat sections of fresh frozen human pancreas. ICA were observed in 53% of patients. At the time of diagnosis 76% of children and 14% of adults were positive for ICA. In the remaining group of patients ICA were observed in 40% of children and 64% of adults. CF-ICA were present only in the ICA positive sera (47%). ICA titres were 1:1-1:128, CF-ICA titres were 1:1-1:8. There was no linkage between ICA and CF-ICA titres. The residual beta cell function was measured by serum C-peptide. There was no association between presence of ICA and residual beta cell function. The patients having CF-ICA had a significantly higher endogenous insulin secretion in comparison with the patients who were ICA negative. PMID- 2099112 TI - [Methods for studying the sperm fertilizing capacity]. AB - Spermatozoa achieve their fertilizing capacity through numerous biocellular changes occurring in male and female genital tracts. From testicular production to male pronucleus formation, the aim of this study is to point out the various laboratory techniques which have been developed to assay semen fertilizing capacity. Most assessments only investigate one of the aspects of sperm fertilizing ability, IVF only can appraise the whole process. PMID- 2099113 TI - [Urinary iodide determination by X-ray fluorescence]. AB - Urinary iodide measurement has been carried out by X-ray-fluorescence, either directly on urinary solution, or after matrix concentration. Proportionality between emitted XK alpha rays of iodine and iodide mass in standards has been observed on a large scale, ranging up to 400 micrograms. With an exciting-1.11 GBq (241(95) Am)-radioactive source, 0.44 microgram are detected for solid matrix, and 0.9 microgram/ml for iodide in solution for 10 mn measuring time. So direct measurement on solution can be applied only to high excreted iodide. For normal range iodide determination is performed after anionic resin concentration (on 100 ml or 200 ml). For tracing, Na I131 is employed. The binding ratio is strongly depending on flow, resin weight, and associate urinary anionic components. On 20 healthy subjects, normal range value is 53 +/- 22 micrograms/l (m +/- s.d.). Comparative study with an electrochemical method showed fluorescence iodide values are lower than the former. The proposed method is very simple, one or two steps (function of iodide content). As no interfered Rx has been observed in the Rx iodide region, the authors can ascertain that accurate values are observed by X-ray fluorescence. In case of high iodide content, this methods allows to distinguish urinary iodide versus total urinary iodine, when performing solution and matrix concentration studies on the urinary batch. PMID- 2099114 TI - [Phenotypic and functional study of natural killer lymphocytes in flow cytometry: application to renal transplantation]. AB - In order to define the best appraisal of Natural Killer cells, the authors performed a dual study, including both phenotypes and functional activities, and all the analyses were achieved with flow cytometric techniques. Results were applied to renal transplantation. Among the numerous clusters of differenciation, only CD16 and CD56 appeared to be well correlated with the functional properties of Natural Killer cells, and especially for CD3- cells. On the other hand, CD57 should no longer be considered as a NK marker. Functional properties of Natural Killer cells were evaluated by cytotoxicity assays of peripheral lymphocytes against K562 and Daudi tumor cells, either spontaneously, or after a 3-day activation with Interleukin 2 (LAK). The authors use carboxyfluoro-diacetate to label viable cells and avoid radioisotopes. They confirm the Natural Killer cells deficiency in renal transplant recipients, and show that this impairment also involves the LAK cytotoxicity. Azathioprine appeared to be responsible of such deficiency. During viral infections, Natural Killer cells raised and reached the normal values, while they were incapable of any response to fight against cancer. They suggest that the Natural Killer deficiency could explain the high incidence of malignancies during renal transplantation. PMID- 2099115 TI - Biosensors for directly measuring cell affecting agents. AB - Cellular perfusion chambers have been constructed from the Light Addressable Potentiometric Sensor (LAPS) previously described. The authors have used these chambers to measure the effects of a variety of agents on the metabolic rates of cells. The chambers are used in a stopped flow mode. When flow is on, samples may be introduced to the chamber. When flow is stopped, acidification of the very small volume of medium in the chamber is used to determined the metabolic rate of the cells. Using a variety of types of mammalian cells the authors have demonstrated the following. The triggering of cellular receptors can be determined in minutes. Metabolic inhibition of normal human cells by a test compound can be correlated with the compounds in vivo ocular irritancy. And the efficacy of chemotherapeutic agents on tumor cells exhibiting multidrug resistance can be determined in a few hours. PMID- 2099116 TI - Immunoassays and nucleic acid detection with a biosensor based on surface plasmon resonance. AB - A technique based on surface plasmon resonance is described which can be used to detect changes of refractive index that occur when one partner of a molecular binding pair diffuses from solution to bind the other partner which is immobilised on a silver surface. Results for the molecular binding pairs; protein antibody, hapten-antibody and DNA-DNA are described. Instrumentation necessary for implementation of the technique is detailed. Immunoassay of proteins and haptens is possible in less than one minute with a sensitivity of 10(-9) mol/l. Hybridisation of 10 fmoles of a 97 base target sequence on the 1 mm2 area of detection to an immobilised oligonucleotide probe can be detected in less than five minutes. Advantages of the technique include the ability to record the kinetics of binding reactions in "real time" and the lack of labels in this simple assay format. Methods of improving the sensitivity are discussed. PMID- 2099117 TI - Covalent immobilization of biomolecules onto polystyrene MicroWells for use in biospecific assays. AB - Modification of polystyrene for higher binding capacity and/or for specific covalent immobilization of biomolecules is discussed. The benefit of covalent coupling of biomolecules onto a new commercially available surface type for covalent immobilization, CovaLink NH, is illustrated. The CovaLink NH solid phase has spacer arms covalently grafted onto the polystyrene solid phase, approximately 10(14) groups/cm2. Coupling procedures for covalent immobilization of biotin and peptides are demonstrated, and the advantage of using carbodiimide for coupling of carboxylic acid containing compounds is shown. PMID- 2099118 TI - Antigen-binding activity of antibodies immobilized on styrene copolymer beads. AB - An important element of the Kodak thin-film immunoassay is antibody immobilized on small polymer beads. Monodisperse styrene copolymer beads offer a well defined, high surface area substrate for covalent immobilization of monoclonal antibodies. The authors have used the ability of an immobilized monoclonal antibody directed against phenobarbitol, Phe 1.9, to recognize an antigen-enzyme conjugate to determine the extent of antibody activity retention and find that the packing density of antibody at the surface and the copolymer composition are important variables. For polystyrene homopolymer and some copolymers, antibody retention is greater as the packing density at the surface increases. Small changes in the copolymer composition, such as addition of 1% acrylamide or 10% acrylic acid, significantly increase the retention of binding activity of the antibody. The chemistry for covalent coupling of the antibody to the surface is also important. Phe 1.9 coupled to chloromethyl styrene copolymer beads retains less activity than when coupled to vinyl sulfone copolymer beads. Monodisperse sytrene copolymer beads provide great flexibility in the design of rapid immunoassays since a copolymer bead can be tailored to the specific requirements of the antibody and the analyte. PMID- 2099119 TI - Multispot, multianalyte, immunoassay. AB - Consideration of the basic principles of immunoassay design reveals that highly sensitive assays can, in principle, be developed using amounts of "sensor" antibody far smaller than are currently conventional in this field. Furthermore, when using such amounts, the fractional occupancy of antibody binding sites by analyte is independent of both sample volume and antibody concentration. Labelling of both the sensor-antibody and a developing antibody (designed to recognize either occupied or unoccupied sensor-antibody binding sites) permits the development of "ratiometric" immunoassays relying on measurement of the ratio of signals emitted by the two labelled antibodies. Furthermore, the sensor antibody can be located within a "microspot" a few microns 2 in area. By labelling both sensor and developing antibodies with fluorescent labels, and scanning the microspot using a highly focussed laser beam, microspot immunoassays at least comparable in sensitivity with conventional "macroscopic" immunoassays are made possible. This in turn permits the development of immunoassay "arrays" capable in principle of measuring very large numbers of different substances within small samples (such as a drop of blood). The general principles and theory underlying these concepts are discussed, and preliminary experimental data using currently available instrumentation reported. PMID- 2099120 TI - [In vitro effects of argon laser radiation the human healthy and atherosclerotic aorta]. AB - Argon laser exposures in vitro were done on human aortas. The laser energy applied on a fresh aorta section (A) was from 100mw to 1000mw. A second aorta section (B), formalin fixed, was irradiated under saline solution by a fiberoptic system. Laser energy was from 400mw to 720mw. The time exposures were all different in both sections. A and B histologic findings of thermal damage were similar Three zones of tissue injury were observed: I) crater because of tissue vaporization; II) coagulative necrosis surrounding it; and III) multiple vacuoles in the adjacent tissue produced by acoustic or shock injury. Tissue damage was related directly with total energy delivered: less than or equal to 500mw showed inner vascular wall necrosis, and at greater than or equal to 720mw it was perforated. Atherosclerotic tissue was more resistant to laser thermal injury than normal tissue. We could not find time relation with thermal damage. This preliminary information is an early step for the possible use of Argon laser on cardiovascular area. PMID- 2099121 TI - [Color doppler-echocardiography study of the triatrial heart]. AB - Two-dimensional echocardiography has proved its utility in the diagnosis of cor triatriatum sinister by visualizing the defect and its relation to the other structures. Recently pulsed and continuous wave Doppler have been used to determine the degree of obstruction of the membrane. In this study we present three patients with ages six, eight and fourteen months respectively, all with a clinical history of growth retardation, respiratory infections and dyspnea. The patients were studied with two-dimensional and color flow Doppler echocardiography. In all, a membrane was visualized, which divided the left atrium in two chambers, a superior one which received the pulmonary veins and an inferior in continuity with the mitral valve and the left atrial appendage and with color flow Doppler the absence of obstruction at this level was demonstrated. In one patient besides the anomaly of cor triatriatum complete transposition of great arteries with pulmonary stenosis was diagnosed and in another one, patent ductus arteriosus and ventricular septal defect. Diagnosis were confirmed by hemodynamic studies. It is concluded that the color flow Doppler is a diagnostic method of great utility because it permits to obtain more information which complements conventional echocardiography. PMID- 2099122 TI - [The effect of psyllium plantago in slightly to moderately hypercholesterolemic patients]. AB - The hypocholesterolemic effect of psyllium plantago (PP) was evaluated in 14 individuals with polygenic hypercholesterolemia. Subjects with secondary dyslipidemias were excluded. Since their admission until the end of the study all the patients had to follow an isocaloric diet, with less than 10% of the calories provided as saturated fats, P/S relation greater than 1 and daily intake of less than 300 mgr of cholesterol. The study was divided in two stages; the first one, from week -6 to 0 evaluated exclusively the response to diet, and the stage II, from week 0 to +12, evaluated the response to PP. The PP in envelopes with 3.4 grs each, was taken dissolved in water three times daily before meals. In the weeks -6, 0, +4, +8 and +12 were done lipid profiles that included; total cholesterol, triglycerides, and high density cholesterol. Cholesterol of the low density lipoproteins was obtained with the formula of Friedewald modified by De Long. The use of PP produced at week 12 a reduction of 8% in total cholesterol and 11% in LDL cholesterol. With non significant changes in triglycerides and HDL C. We conclude that PP can be used as a complement of diet in the management of polygenic hypercholesterolemia. PMID- 2099123 TI - [Rheumatic carditis in the adult. Anatomoclinical correlation]. AB - The histologic findings of 325 necropsies of rheumatic patients at the National Institute of Cardiology in Mexico, between 1980-1985 were studied forty five of them had Aschoff nodules plus valvular inflammation-Out of these 45 cases two groups were formed: children-adolescent group (24 cases) and an adult group (21 cases). The clinical, histologic and laboratory findings were compared. Clinical records were reviewed searching for history of rheumatic fever. Active rheumatic fever was suspected in 16 patients in the younger group (67%) and only in 3 adults (14.2%). As far as Jones' criteria is concerned, the most common finding was carditis, principally in the younger group (83%). In the adult group, it appeared in 50% of the patients. All other criteria were only occasionally seen or could not be identified during the patients lifetime. The most common laboratory finding which could suggest active rheumatic fever were: a high levels of anti-streptolysin in younger patients (95%) and elevation of erythro sedimentation in adults (83%). We conclude that in active rheumatic fever of the adult; Jones criteria are not met, so the illness is difficult to recognize, and there is clinical-histologic discrepancy. In this context the disease has a "silent" evolution. PMID- 2099124 TI - [Surgical alternatives in the treatment of double-outlet right ventricle]. AB - Double-outlet right ventricle (DORV) is a type of ventriculo-arterial connection, in which both great arteries are connected to the morphologically right ventricle in at least 50% of their diameter. The relation of the great arteries with the ventricular septal defect (VSD) and the pulmonary stenosis, are important anatomical aspects in the election of the surgical technique. In this study we describe four patients with DORV, in whom different surgical techniques were used according to the specific anatomy of each case. Two patients had subaortic restrictive VSD, with subpulmonary stenosis in one of them. In the other two patients the VSD was subpulmonary with the aorta anterior and to the left, in one of these existed moreover a severe mixed pulmonary stenosis. It is concluded, that with different surgical techniques according to the specific anatomy of each patient, good results can be obtained in the surgical treatment of these complex congenital malformations. PMID- 2099125 TI - [The prevalence of IgG anticardiolipin antibody at the anticoagulant clinic of the Ignacio ChavezNational Institute of Cardiology. I. Unselected population]. AB - The recently described antiphospholipid antibodies syndrome (APA) is recognized because recurrent abortion, thrombocytopenia and repeated arterial and/or, venous thrombosis plus the demonstration of serum antibodies reactive with anionic phospholipids. We studied 51 patients who attend the anticoagulation clinic at our Institute. In a representative sample, we search for serum IgG specific for cardiolipin using an standard assay. We did not pick up unrecognized APA cases. The low frequency of this condition could be an explanation for our negative results in non-selected cases. Besides, this study denies a relationship between the chronic use of coumarin anticoagulants and development of peculiar antibodies. PMID- 2099126 TI - [Myocardial infarct in diabetes mellitus: short- and long-term prognostic factors]. AB - To determine the evolution of acute myocardial infarction in patients with diabetes we study 207 consecutive patients with myocardial infarction. Using WHO's criteria 23% of our cases were diagnosed of diabetes mellitus. Diabetic patients were older than non diabetic (67.9 +/- 10 years vs. 62.4 +/- 11 years, p less than 0.05) and had a higher ratio of females (52% vs. 21%, p less than 0.001). Cigarette smoking was infrequent in diabetic population. Incidence of other risk factors was comparable. Despite an increased proportion on no q-wave myocardial infarction in the diabetic patients (12.5% vs. 6.9%, p NS), the site of infarction was similar into the two groups. Acute phase mortality was higher in the diabetic group (37.5% vs. 16.3%, p less than 0.001). This increased mortality is, partially, related to an increased incidence of pump failure, but a multivariate analysis using stepwise logistic regression, selected diabetes as an independent predictor of prognosis. Survivors were followed for 41 +/- 20 months; diabetic patients showed a poor prognosis with a higher incidence of congestive heart failure (42.8% vs. 13.7%, p less than 0.01), reinfarction (16.6% vs. 8.5%) and death. Cox proportional hazard model selected diabetes as an independent predictor of survival. We conclude that patients with diabetes mellitus constitute a subgroup into the myocardial infarction population; this subgroup had greater mortality than non diabetic patients in relation to increased incidence of pump failure, but multivariate analysis indicates that other factors not considered in the present study may play a role in their poor prognosis. PMID- 2099127 TI - [The effect of acute hyperinsulinemia on arterial pressure in healthy individuals]. AB - To assess if induced hyperinsulinemia enhances blood pressure (BP), three tests were performed to nine healthy volunteers as follows: A. After an oral dextrose load (75 g), 250 ml of 0.9% NaCl plus 25 g dextrose were infused in three hours. B. The same procedure, plus 15 U of regular insulin in the intravenous solution. C. (control) The same procedure but without insulin and dextrose. Pulse and BP were measured every 15 minutes, serum glucose and insulin were determined hourly. Hyperinsulinemia from 2 to 7-fold the basal value was induced in the test A, and from 7 to 30-fold in the test B (P less than 0.01). BP did not rise with hyperinsulinemia, but a slight and nonsignificant decrease of mean BP and higher heart rate (P less than 0.05) were noticed at the third hour in the test B. Acute hyperinsulinemia do not cause high BP. A cause-effect relationship between hyperinsulinemia and hypertension is still unproved. PMID- 2099129 TI - [Substrate oxidation in the myocardium]. PMID- 2099128 TI - [Arterial blood pressure in various groups in the urban population of Morelia City]. AB - Four groups from a urban population of Morelia were inquired, to determine frequency of high blood pressure and provide basic information of arterial hypertension in relation with other variables; 2638 persons were checked. Age ranged from 10 to 90 years, (771 men, 1867 women). Age, sex, weight and height were also measured. Evaluations were performed in the morning with mercury sphygmomanometer registering first and fifth korotkoff's sounds in orthostatic position with a second selective evaluation in sitting position. Availability of medical services and knowledge about presence of arterial hypertension were also evaluated. Blood pressure and prevalence of hypertension had similar behavior with regard to age: pressure recordings were higher in men before 40 years. After this age were higher in women. In general, 14% had high blood pressure, in the second evaluation this value dropped to 7%. For 11% of the studied population, high blood pressure had been previously recorded 7 out of 10 cases of hypertension did not have any control. Three of them had not information about this illness. We found a positive correlation between weight and blood pressure (p less than 0.001) specially among women. PMID- 2099130 TI - Effects of triglycylvasopressin on portal pressure and portal bile acid concentration in normal and cirrhotic rats. AB - The effects of triglycylvasopressin on portal vein pressure and portal bile acid concentration after oral loading with chenodeoxycholic acid were evaluated in normal and cirrhotic rats. Triglycylvasopressin significantly reduced the portal vein pressure and portal bile acid concentration in both populations (normal: portal vein pressure 21.2%, p less than 0.05; portal bile acid concentration 43.2%, p less than 0.005; cirrhotic: portal vein pressure 19.8%, p less than 0.025; portal bile acid concentration 20.3%, p less than 0.05). Both in normal and cirrhotic rats, portal vein pressure and portal bile acid concentration resulted correlated. These results support that the combined determination of portal vein pressure and portal bile acid concentration could represent an interesting approach to the study of drugs which are potentially active on portal circulation and could indirectly provide information as to portal flow. PMID- 2099131 TI - Pharmacological properties of YM264, a potent and orally active antagonist of platelet-activating factor. AB - The anti-platelet-activating factor effect of YM264 was examined in a variety of in vitro and in vivo test systems. YM264 inhibited [3H] platelet-activating factor binding to rabbit platelet membranes with a pKi value of 8.85. YM264 inhibited the platelet-activating factor-induced human, rabbit and guinea-pig platelet aggregation with pA2 values of 8.68, 8.33 and 8.14, respectively. However, at 10(-4) M the compound did not affect rabbit and human platelet aggregation induced by ADP, collagen arachidonic acid and epinephrine. YM264 reversed a platelet-activating factor-induced hypotension is anesthetized rats with an ED50 value of 0.005 mg/kg, i.v. Administered orally, YM264 inhibited platelet-activating factor-induced death in mice, hemoconcentration in rats and increase in vascular permeability in guinea-pigs with ED50 values of 0.19, 0.30 and 0.49 mg/kg, p.o., respectively. YM264, at 1 and 3 mg/kg, p.o., showed a significant anti-platelet-activating factor effect in a rat hemoconcentration model up to 6 hr after treatment. Moreover, in ex vivo experiments in guinea pigs, YM264, at the doses of 0.3 to 3 mg/kg, p.o., shifted the dose-response curves of platelet-activating factor-induced platelet aggregation to the right in a parallel manner. These results indicate that YM264 is a selective, potent and orally active platelet-activating factor antagonist. PMID- 2099132 TI - Acute administration of the antidepressant trazodone increases noradrenergic locus coeruleus neuronal firing in rats. AB - Extracellular single-unit recordings were made from noradrenergic locus coeruleus neurons in chloral hydrate-anesthetized male Sprague-Dawley rats. Acute intravenous administration of the antidepressant trazodone produced a mild excitation of firing of these cells (ED25 = 0.128 mg/kg; ED50 = 0.659 mg/kg). These findings, in combination with previous work showing that trazodone inhibits the firing of serotonergic dorsal raphe neurons indicate that trazodone modulates monoaminergic neuronal activity in the brain and suggest a unique electrophysiological profile for this drug among antidepressants. PMID- 2099133 TI - Antidiabetic activity of MTP-3115 in normal and diabetic mice. AB - MTP-3115 is a newly-synthesized thiopyranopyrimidine compound with a structure similar to that of MTP-1403 and MTP-1307. However, the biological profile of MTP 3115 is different from that of MTP-1403 and MTP-1307 (previously reported). Similar to MTP-1403 and MTP-1307, MTP-3115 improves glucose tolerance in both normal and obese-diabetic viable yellow mice with equal potency. However, unlike MTP-1403 and MTP-1307, MTP-3115 also lowers blood glucose of fed and fasted normal and obese-diabetic viable yellow mice. Although the mechanisms of action of MTP-3115 are not elucidated, it is unlikely that its mode of action is similar to that of sulfonylureas because tolbutamide neither improves glucose tolerance nor lowers blood glucose in obese-diabetic viable yellow mice. PMID- 2099134 TI - Pharmacological action of YM737, a new glutathione analogue, in rats with experimental hematoma. AB - The effects of YM737, a glutathione analogue, and glutathione on neurological deficits and cerebral malondialdehyde concentrations were investigated in rats with experimental hematoma. A unilateral cerebral hematoma was provoked by injecting 0.25 ml of autologous blood around the capsula interna, putamen and caudate nucleus of the left cerebral hemisphere of the rat. Drugs were administered daily for four days beginning immediately after the operation. Neurological deficits and cerebral malondialdehyde concentrations were measured daily for 4 days. In the vehicle-treated group, deficits reached a maximum on the second day after the operation and then gradually recovered. YM737 (300 mg/kg, i.p.) accelerated recovery from neurological deficits, while glutathione had no effect. YM737 (300 mg/kg, i.p., on the fourth day after the operation) reduced the increase in malondialdehyde concentrations. Our results suggest that YM737 improves neurological deficits in this cerebral hematoma model, presumably partly due to inhibition of the lipid peroxidase response. PMID- 2099135 TI - Modifications on dopaminergic and cholinergic systems induced by the water tank technique: analysis through yawning behavior. AB - Animals deprived of REM sleep by the water tank technique show an important decrease in frequency of yawning, induced by dopaminergic (apomorphine in low doses) and cholinergic (physostigmine and pilocarpine) agonists, if they are tested immediately after the 96 hr of deprivation. In order to understand the mechanisms underlying the effects of REM sleep deprivation on dopaminergic and cholinergic systems, we decided to test the animals after a recovery period of 24 hr. It was observed that apomorphine-induced yawning was still significantly reduced, whereas pilocarpine-induced yawning had returned to normal. The findings suggest that REM sleep deprivation alters dopaminergic and cholinergic systems in different ways: it seems that the interference on the dopaminergic system is prior and stronger than on the cholinergic system, thus its recovery demands more time. PMID- 2099136 TI - Muscarinic receptor subtypes of guinea-pig gallbladder smooth muscle. AB - The antagonism of acetylcholine-induced contractions of guinea-pig gallbladder and ileum smooth muscle strips via various antagonists has been investigated in order to find out the muscarinic receptor subtype(s) of gallbladder smooth muscle. Atropine, pirenzepine, 4-DAMP and AF-DX 116 were used as nonselective, M1 selective, M1- and smooth muscle M3-selective and cardiac M2-selective muscarinic antagonists, respectively. All the muscarinic antagonists examined displaced the concentration-response curves to the right parallelly in a concentration dependent manner without affecting the maximum response in both tissues. Schild analysis of data was consistent with competitive antagonism. pA2 values of the antagonists were as follows: a) gallbladder: atropine: 8.43; pirenzepine: 7.81; 4 DAMP: 8.10; AF-DX 116: 6.71; b) ileum: atropine: 9.62; pirenzepine: 6.94; 4-DAMP: 9.41; AF-DX 116: 6.55. It may be concluded that the muscarinic receptors of the guinea-pig gallbladder, which mediate acetylcholine-induced contractions, are not of the cardiac M2-subtype and may be distinguished from ileal smooth muscle M3 receptors because 4-DAMP has a 20.4 times greater affinity for ileal smooth muscle muscarinic receptors. PMID- 2099137 TI - Effects of ephedrine and phenylpropanolamine on the antinociceptive effects of morphine and codeine in mice. AB - The effects of ephedrine and phenylpropanolamine on the antinociceptive activities of morphine and codeine were investigated. Both morphine and codeine exhibited dose-dependent antinociceptive activities in the tail flick test. Ephedrine (5, 10 and 20 mg/kg) and phenylpropanolamine (5, 10 and 20 mg/kg) showed no antinociceptive effect when administered alone. The antinociceptive effects of morphine were enhanced in mice pretreated with ephedrine or phenylpropanolamine. similarly, codeine antinociception was increased in mice pretreated with ephedrine or phenylpropanolamine. In all cases, the ED50 values and single dose comparisons were shifted in the same direction. These effects on the antinociceptive potencies of morphine and codeine were found to be dose dependent, being statistically significant at the higher dose levels of ephedrine and phenylpropanolamine used in the present study. PMID- 2099138 TI - Structure-activity relationship for the inotropic effect of aromatic methyl-p quinones. AB - The structure-activity relationship of a novel natural substance murrayaquinone-A and related compounds, was studied by evaluating their positive inotropic potencies on guinea-pig papillary muscle in Krebs-Henseleit solution. Among the selected eight compounds, menadione and plumbagin (aromatic methyl-p-quinone) induced a potent triphasic inotropic response, as reported previously for murrayaquinone-A. The order of potency of these active compounds was: plumbagin (pD2 = 6.40) greater menadione (pD2 = 5.70) greater than murrayaquinone-A (pD2 = 5.27). Demethyl derivatives of aromatic methyl-p-quinones (carbazolequinone, 1,4 naphthoquinone and 2-hydroxy-1,4-naphthoquinone) and methyl-benzoquinones (co enzyme Q10 and 2-methyl-1,4-benzoquinone) did not produce any positive inotropic effect. It is concluded that the presence of the aromatic methyl-p-quinone skeleton is essential for the development of an inotropic response. A common mechanism for this positive inotropic effect is suggested by the fact that in all cases it was triphasic in nature and inhibited in anoxic conditions or by 2,4 dinitrophenol and dicumarol. PMID- 2099139 TI - [Traumatic rectal injuries]. AB - The authors review the cases of traumatic rectal injuries admitted to the Emergency Service of the "Hospital das Clinicas", University of Sao Paulo Medical School, during the period of July 1981 to July 1988. Forty-five patients (62.5%) had their injuries due to gunshot, 14 (19.4%) due to foreign bodies on the rectum, 10 (13.8%) due to blunt trauma and 3 (4.1%) due to stab wounds. The intraperitoneal rectum was injured in 32 patients (44.4%) and extraperitoneal portion of the rectum in 40 patients (55.5%). On the intraperitoneal injuries the management adopted were simple suture (14 patients), associated with a colostomy (17 patients) and in one patient the Hartmann procedure was adopted. On the extraperitoneal wounds the management adopted were rectal repair (when feasible), colostomy, distal washout and drainage. The complications rate was 27.8%, and from them, the majority (70%) were related to infectious nature. Seven patients died (9.7%), four of them as a consequence of sepsis. The morbidity and mortality of the rectal injuries were closed related to infectious complications as a consequence of late diagnosis. For this reason, the authors consider that all efforts should be employed to establish the prompt diagnosis. PMID- 2099140 TI - [Surgical treatment of ascites with Le Veen shunt in patients with alcoholic liver disease]. AB - Studies were carried out on 16 alcoholic cirrhotics with clinically intractable ascites who underwent the implant of peritoneovenous (LeVeen) shunts. Our purpose was to find out how this group of patients responded to this kind of surgical treatment for ascites. Fifteen of these patients were male and one female, with a median age of 51.3 years. According to Child classification, 7 were Child B and 9 Child C. Thirty-three surgeries were conducted, in that 5 were performed for revision of the shunt positioning and 12 for the replacement of the valves. A total of 28 shunts were used. Postoperative immediate mortality occurred in 5 patients (4 Child C and one Child B). The median late postoperative follow-up of the 11 patients who survived was 25.8 months. We concluded that LeVeen shunt implantation is a valid palliative therapeutic resource for the treatment of ascites in alcoholic cirrhotics. The results obtained with this patient population are similar to those observed in cirrhotics who presented other etiologies. We also concluded that late mortality was not related to the implant of a LeVeen shunt but was due to the normal course of the disease. PMID- 2099141 TI - [Colonoscopy in Crohn's disease of the colon]. AB - The author's experience with 42 colonoscopies in 41 patients with barium enema diagnosis of Crohn's disease is presented. The radiologic, endoscopic, histologic and surgical results are compared. According to radiological localization, the patients were classified in these groups: anorectal (9.7%), colic (51.2%) and ileocolic (39.1%). In 34 patients (80.9%) the endoscopic appearance was compatible with Crohn's disease, and in 24 (70.5%) the histologic examination confirmed the diagnosis. Endoscopic findings were as follows: segmental lesions in 34 (100%), aphthous ulcers in 18 (52.9%), cleft-like ulceration in 24 (70.5%) and cobblestone mucosa in 28 (82.3%). In 8 patients where endoscopy was not suggestive of Crohn's disease, the histologic examination was also negative, showing that colonoscopy was better than barium enema. Twenty patients with endoscopic diagnosis of Crohn's disease were operated and the diagnosis was confirmed in all. Endoscopic biopsies were positive in 12 (60%) of these operated patients. The author concludes that the endoscopic diagnosis of Crohn's disease can be made regardless of biopsy results. PMID- 2099142 TI - [Malignant peritoneal pseudomyxoma. A case report]. AB - A case of malignant pseudomyxoma peritonei is described. This rare entity is characterized by widespread dissemination throughout the abdominal cavity and low grade of malignancy. General well-being is usually unimpaired. Diagnosis can be suggested by computed tomographic appearance; the course of action, however, is ultimately determined by the operative findings. The best treatment has been tumour excision, although the extent of this procedure is not well defined. PMID- 2099143 TI - [Human gastroenteritis associated with Vibrio fluvialis in Recife]. AB - Due to the low number of reports about vibrio gastroenteritis in Brazil, it was decided to report one case of human gastroenteritis from who only Vibrio fluvialis has been found in patient stools. The main clinical epidemiological and microbiological aspects related to that microorganism are discussed. Probably, this is the first report of gastroenteritis caused by Vibrio fluvialis in the country. PMID- 2099144 TI - [Celiac disease associated with insulin-dependent diabetes mellitus: report of a case]. AB - We report the association of diabetes mellitus and celiac disease in one patient, which was confirmed by intestinal biopsy, the withdraw of gluten from the diet, and by a positive challenge test. We emphasize the importance to recognize this association to improve the clinical management of patients with diabetes mellitus. PMID- 2099145 TI - [Records of clinical research of the Institute of Gastroenterology of Sao Paulo and the Brazilian Institute of Studies and Research in Gastroenterology]. PMID- 2099146 TI - Cycloheximide enhances factor binding to the native 40S ribosomal subunit of Microsporum canis. AB - Native and derived ribosomal particles from the mycelial cells of Microsporum canis grown in the presence and absence of cycloheximide were compared by CsCl equilibrium density gradient centrifugation. Since the buoyant densities of ribonucleoprotein complexes are dependent on the protein-RNA ratio, they reflect the composition of these particles. The native monosomes from cells grown in the presence and absence of cycloheximide had a buoyant density of 1.585 g/cc. The native 60S subunits showed a density of 1.540 g/cc from cells grown in both presence and absence of cycloheximide, while the derived subunits showed a density of 1.610 g/cc. The derived 40S subunits had a density of 1.550 g/cc while the native 40S showed a major species of density 1.535 g/cc with three other minor species ranging in densities from 1.450-1.390 g/cc. The mycelia grown in the presence of cycloheximide showed an increased proportion of native 40S subunits in the density range of 1.450-1.390 g/cc, indicating that the drug enhances factor binding to native ribosomal subunits in M. canis. PMID- 2099147 TI - Highly sensitive enzyme immunoassay for beta-nerve growth factor (NGF): a tool for measurement of NGF level in rat serum. AB - A sensitive two-site enzyme immunoassay (EIA) system was established for mouse beta nerve growth factor (NGF) isolated from mouse submaxillary gland. Our EIA system is based on the sandwiching of antigen between anti-mouse beta NGF antibody IgG coated on a polystyrene plate and biotinylated anti-mouse beta NGF antibody IgG. The bound antibody complex was quantified with streptavidin linked beta-D-galactosidase (beta-D-galactosidase, EC 3.2.1.23). With this system NGF concentrations as low as 0.02 pg/well (corresponding to 8 x 10(-19) mol) could be measured reproducibly. The sensitivity of this EIA system permitted the quantification of endogenous immunoreactive beta NGF in rat serum. The mean level in serum of male rats (153.2 pg/ml) was found to be almost the same as that of female rats (127.6 pg/ml). PMID- 2099148 TI - Identification of a human stomach alcohol dehydrogenase with distinctive kinetic properties. AB - A new form of alcohol dehydrogenase, designated mu-alcohol dehydrogenase, was identified in surgical human stomach mucosa by isoelectric focusing and kinetic determinations. This enzyme was anodic to class I (alpha, beta, gamma) and class II (pi) alcohol dehydrogenases on agarose isoelectric focusing gels. The partially purified mu-alcohol dehydrogenase, specifically using NAD+ as cofactor, catalyzed the oxidation of aliphatic and aromatic alcohols with long chain alcohols being better substrates, indicating a barrel-shape hydrophobic binding pocket for substrate. mu-Alcohol dehydrogenase stood out in high Km values for both ethanol (18 mM) and NAD+ (340 microM) as well as in high Ki value (320 microM) for 4-methylpyrazole, a competitive inhibitor for ethanol. mu-Alcohol dehydrogenase may account for up to 50% of total stomach alcohol dehydrogenase activity and appeared to play a significant role in first-pass metabolism of ethanol in human. PMID- 2099149 TI - Effects of some protein-reactive compounds on K+ flux into mitochondria. AB - The pathway of unidirectional K+ flux into respiring mitochondria is sensitive to the protein reactive compounds mersalyl and dicyclohexylcarbodiimide (DCCD). When treated with either of these reagents, mitochondria retain sensitivity to other reagents which affect K+ flux into untreated mitochondria. The present studies show that the K+ influx mechanism modified by pretreatment with DCCD remains sensitive to inhibition by quinine. K+ influx stimulated by mersalyl, in the absence of exogenous Ca++, retains sensitivity to inhibition by quinine and to some extent by Mg++. The results support the conclusion that K+ uptake by mitochondria modified by mersalyl or DCCD occurs via the same proteinaceous pathway as that which mediates K+ uptake by untreated mitochondria. PMID- 2099150 TI - Cytochrome P-450 catalyzed redox cycling of orthophenylphenol. AB - o-Phenylphenol was converted to 2,5-dihydroxy biphenyl (phenylhydroquinone) by microsomal P-450. Depending on the cofactor used, microsomal enzymes catalyzed oxidation and/or reduction of phenylhydroquinone. Phenylhydroquinone was oxidized to phenyl 2,5'-p-quinone by cumene hydroperoxide-supported microsomal P-450. Phenyl 2,5'-p-quinone was reduced to phenylhydroquinone by cytochrome P-450 reductase. This study provides direct evidence of cytochrome P-450 catalyzed redox cycling of o-phenylphenol. It is postulated that redox cycling of o phenylphenol may play a role in o-phenylphenol-caused bladder cancer. PMID- 2099151 TI - Phosphate and pepsin adsorptions by a new boehmite compound and aluminum hydroxide. AB - A new microcrystalline compound of aluminum oxide hydroxide (tentatively named PT A) was synthesized in the hope of providing a better phosphate adsorbent for future clinical use than the currently marketed aluminum hydroxide gels (ALG). An X-ray diffraction study demonstrated a boehmite structure in PT-A but an amorphous structure in ALG. PT-A was more stable in pH change than ALG; in elution tests in artificial gastric and intestinal solutions, aluminum ion eluted from PT-A was maximally 10% of the amount from ALG at pH 1.2; and was undetectable at pH 6.8, at which point ALG still showed some aluminum elution. Phosphate-adsorbing efficacy of PT-A and ALG in vitro was about the same at pH 1.2; however, it was four times greater in PT-A than in ALG at pH 6.8, indicating that PT-A will be effective in the intestine. PT-A also adsorbed pepsin but the amount was at most the same or much less than that adsorbed by ALG, which depended on pH in solution. PMID- 2099152 TI - The mammalian genome contains a high proportion of processed pseudogenes corresponding to ribosomal protein L19. AB - The mammalian genome contains multiple copies of ribosomal protein (rp) L19 related sequences. Screening of mouse and rat genomic libraries with cloned rpL19 cDNA yielded seventeen independent lambda Charon 4A recombinant phages containing twelve and five genes for mouse and rat rpL19, respectively. Structural analysis indicated that all of these rpL19 genes contain the entire coding sequence (approx. 700 bp) but lack introns. The nucleotide sequence of a mouse gene (rpL19 17), exhibiting the highest homology with the mouse rpL19 cDNA, revealed genetic lesions which would preclude the translation of an intact protein, from a putative transcript. Based on these features we propose that these clones represent processed genes of which most, if not all, are pseudogenes. PMID- 2099153 TI - Conditions for the extraction of protease-free LMG proteins from calf thymus. AB - Calf thymus LMG proteins are known to be susceptible to a wide variety of chromatin-associated proteases. We have investigated the use of different inhibitors to protect LMG chromosomal proteins from proteolytic degradation. In this work we have developed a preparative method for the extraction of LMG proteins from purified chromatin which provides an LMG protein extract devoid of proteolytic activity. PMID- 2099154 TI - Frontal metabolic deficits in Korsakoff syndrome. PMID- 2099155 TI - One-step sandwich enzyme immunoassay for human laminin using monoclonal antibodies. AB - A one-step sandwich enzyme immunoassay (one step sandwich EIA) for human serum immunoreactive laminin was set up with a pair of monoclonal antibodies prepared against human placental laminin P1 fragment. The assay was characterized by carrying out two immunoreactions simultaneously, laminin P1 fragment reacting with both a monoclonal antibody as a solid phase and a horseradish peroxidase labeled monoclonal antibody (Fab') against human laminin P1 fragment as conjugate. Sensitivity of the immunoassay was 0.01 ng/well (0.5 microgram/l), and linearity was obtained between 0.01-20 ng/well (0.5-1,000 micrograms/l). The levels of laminin in sera from normal individuals and patients with liver cirrhosis, hepatocellular carcinoma and primary biliary cirrhosis were 103 +/- 15 micrograms/l, 228 +/- 70 micrograms/l, 341 +/- 163 micrograms/l and 232 +/- 93 micrograms/l, respectively. Protein immunoblotting showed that the serum immunoreactive laminin measured by the assay was a fragment with rel mol mass of 200 kDa. PMID- 2099156 TI - Changing arrangements and improving economics of dental practice in the State of Ohio. PMID- 2099158 TI - Ampicillin and sulbactam pharmacokinetics and pharmacodynamics in continuous ambulatory peritoneal dialysis (CAPD). AB - The fixed combination antibiotic ampicillin/sulbactam may provide a new, safe, and effective method of treating dialysis-related bacterial peritonitis. The pharmacokinetics of this antibiotic combination were determined in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The pharmacodynamic activity of this drug was also determined by use of mean bactericidal titers against selected bacterial strains. Six noninfected CAPD patients in a randomized two-way crossover study were given a fixed dose of ampicillin (2 gm) and sulbactam (1 gm) either intravenously or intraperitoneally. The mean peak ampicillin and sulbactam serum concentrations following intravenous dosing were 170.3 and 87.5 micrograms/mL, respectively. The mean peak serum concentrations of ampicillin and sulbactam following intraperitoneal dosing were 48.0 and 27.8 micrograms/mL, respectively. Absolute bioavailabilities of the intraperitoneal ampicillin and sulbactam doses were 60% and 68%. Both drugs exhibited similar distribution and elimination characteristics. Renal failure markedly reduced drug elimination. Intraperitoneal administration of ampicillin/sulbactam provided satisfactory inhibitory and bactericidal antibiotic titers for most organisms in dialysate at 6 h but not 24 h. Ampicillin/sulbactam (2 gm/1 gm) should be administered every 12 h to patients with peritoneal dialysis-related peritonitis. PMID- 2099157 TI - Effects of outreach intervention on risk reduction among intravenous drug users. AB - Considerable voluntary risk reduction has occurred among IVDUs in New York City. The purpose of the AIDS Outreach Project was to improve upon the existing level of risk reduction by providing information and anonymous HIV testing to street recruited IVDUs. Intake and follow-up interviews were conducted with 121 subjects (44% of 276 at intake), with a mean of 4.5 months between interviews. Significant risk reduction occurred in many drug and sexual risk behaviors, although not in bleach use, and more than half of the subjects continued to engage in high-risk sexual behavior. An analysis of differences in risk reduction between early and later intake groups indicated that external trends were not sufficient to account for observed risk reduction. Among subjects engaged in high-risk behavior at intake, those who injected less or were enrolled in drug abuse treatment were more likely to stop high-risk drug injecting. Subjects who (at intake) engaged in less frequent unprotected sex, or who had had sex with someone with AIDS, were more likely to stop high-risk sexual behavior. The majority of subjects at low risk at intake maintained low-risk behavior. Informational interventions appear to be most successful among those IVDUs already engaging in lower levels of risk behavior. More effective methods are needed for those whose level of risk behavior is greater. These might include peer pressure and distributing bleach (as opposed to only providing information about bleach). PMID- 2099159 TI - Melanomas and other skin neoplasms. Pathology and case reports. PMID- 2099160 TI - Alcohol and the brain. AB - Some of the major effects of alcohol, and alcoholism, on the brain are reviewed, with reappraisal of evidence drawn from brain imaging, neuropathology, clinical psychology, and laboratory experimental work. A hypothesis is developed which may help to account for the wide variability encountered in individual susceptibility to alcoholic brain damage and its varied manifestations. Therapeutic implications are considered. PMID- 2099161 TI - Reducing the use of plain abdominal radiographs in an emergency department. AB - Plain abdominal radiographs are ordered frequently in emergency departments. Previous studies have shown that these radiographs are often requested inappropriately with little likelihood of producing useful information. This study shows that the overall number can be reduced significantly, with little risk to patients, when clear guide-lines are applied. PMID- 2099162 TI - Complaints against accident and emergency department: current trends. PMID- 2099163 TI - The influence of immediate physiotherapy in the out-patient management of acute knee injuries: a controlled study. AB - All patients who presented to our Accident & Emergency Department over a 6-month period with an acute knee injury were randomly assigned to receive either immediate physiotherapy or not prior to further follow up at an out-patient clinic. Patients with trivial injuries not requiring follow up and patients with severe injuries requiring immediate admission were excluded from the study. Patients not immediately referred for physiotherapy could be referred if this was thought necessary at later follow up. There was no statistical difference in the number of outpatient follow up appointments or the length of time to discharge from the clinic between the groups. Those patients referred for physiotherapy immediately had a significantly greater number of total attendances at the physiotherapy department. However more patients in the 'no physiotherapy' group ultimately required arthroscopy for suspected meniscal injury. We conclude that a blanket referral of all acute knee injury patients is unjustified and wasteful of resources. However physiotherapy may be indicated in patients initially suspected of having meniscal injury. PMID- 2099164 TI - The Peterborough lorry explosion, 22 March 1989: an analysis of the hospital response. AB - As a result of the lorry explosion on the Fengate Industrial Estate, Peterborough on 22nd March 1989, 82 casualties arrived at Peterborough District Hospital. Despite the fact that casualties arrived at the A&E Department in large numbers before the Major Accident Plan could be implemented, all of the casualties had been assessed and either admitted or sent home within 3 h of the explosion. In the process several valuable lessons were learned, and their implications are discussed in this paper. PMID- 2099165 TI - [Role of the fibula in distal tibial fracture]. AB - Analysing 1077 fractures of the distal segment of the tibia the author found specific morphologies of the accompanying fibula fractures when axial dislocations exist. In valgus position compression and bending forces induce multifragmentary fractures of the diaphysis or impactions of the metaphysis. In varus position bending and traction forces create simple oblique or transverse fractures. The ligaments of the syndesmosis are rarely ruptured when the fibula is fractured. They may remain undamaged when the fibula is intact. Ruptures of the fibulotalar and fibulocalcanear ligaments are not uncommon. The internal fixation of the fibula remains the first step of the AO-tactics for the operative treatment of Pilon-tibial fractures. The initial axial position must be respected. In valgus cases there will be postoperative compression forces (pillar function), in varus cases traction forces (tension band function) acting on the repaired fibula. Indirect reduction techniques ought to be used for complex fibula fractures. PMID- 2099166 TI - [Bilateral traumatic hip dislocation]. AB - The bilateral hip displacements are discussed. We divide these injuries in posterior, anterior and in an equal bilateral luxations of the hip. All types are rare (120 cases found in the literature), after all most of them are posterior hip luxations. Immobilisation must be considered for eight weeks, partial weight bearing to week ten, after this period full weight bearing can be allowed. Discharge from the hospital after three months. The danger of arthroses and femoral-neck necroses in this bilateral injury is discussed. PMID- 2099167 TI - [Ligament injuries of the upper ankle joint: 10 years experience with a stable shoe]. AB - To avoid cast fixation after injuries of the ankle ligaments, in 1980 we presented a new high top sports-boot with stabilizing plastic sticks on both sides of the shoe as a new method of after treatment; The original Stabil-S shoe. The follow up after 5 and 10 years experience shows good results and cast immobilisation of the ankle joint is practically not used any more for the above mentioned indication. Patients go back to work after 25 days on an average which is about 3 weeks earlier then with cast immobilisation. This is the reason why insurance companies in Europe cover the costs for this kind of after treatment, the Stabil-S shoe. To verify the fibular ligament lesions we use stressed x-ray examination in addition to the clinical tests and the patients history. The indication of operative or conservative treatment is still discussed. The late results however show better stability and function after operative treatment, especially for the group of young and active sport patients. The further development of the Stabil-S shoe will try to obtain a normal gait as well as sufficient stability around the ankle joint. This means mobility for the patient and stability around the ankle joint. PMID- 2099168 TI - [Therapy of humerus fractures of the collum chirurgicum]. AB - From 1978 to 1989 178 patients were treated for humerus fractures of the surgical neck. An examination after an average of 9 months showed in 119 cases of dislocation of the humerus of less than one shaft width no significant differences between conservative and operative treatment. In case of major dislocation of more than one shaft width (n = 59) operative treatment resulted in significantly better functional results in all age groups. A wider indication for operation after 1986 lead to better results even in the elder patients. Younger patients profited by an operative treatment even in case of minor dislocation, especially as regards maximum mobility of the shoulder joint. In most cases percutaneous or open drill-wire osteosynthesis was preferred. It is concluded that in elder patients only humerus fractures of the surgical neck with major dislocations should be operated upon. With younger patients an indication for operative treatment can also be seen in cases with minor dislocation. Nevertheless, the fractures of the proximal humerus, even in case of an increased operative treatment, remain a field of conservative therapy. PMID- 2099169 TI - [Injuries in snowboarding]. AB - Snowboarding is a quickly developing wintersport. The estimated number of snowboarders in Switzerland lies between 20,000 and 30,000 now. There has not been much published about trauma in this sport. This study was carried out in five Swiss hospitals in the winters 1988/89 and 1989/90. The results were compared with the data of a traumatologically oriented general practice. The pattern of trauma was almost identic, and quite similar to the injuries in skisport. With further development of the snowboard technique and material a change of type and decrease of number of injuries in this sport can be expected. PMID- 2099170 TI - [Preventive intraoperative irrigation in wound management with Lavasept. Report of experiences with 1,610 cases]. AB - During the years 1984-1989 in the Surgery department of the Bezirksspital Wattenwil all soft-tissue injuries, beside open articulations, were cleaned with the new antiseptic "Lavasept" in a prophylactic way during operation. We are documenting the astonishingly low incidence of infections as well as the good tolerance of the cleaning substance. PMID- 2099171 TI - [Late vascular damage after unilateral leg amputation]. AB - The higher incidence of infrarenal aortic aneurysms in war-veterans with above knee amputations indicates that leg amputation besides arteriosclerotic risk factors constitutes a relevant pathogenetic factor for the late development of an abdominal aortic aneurysm. A retrospective study of 25 mainly young patients with above knee amputation showed that already one year after leg-loss a typical adaptive narrowing of the pelvic and leg arteries with significant reduction of the flow volume of 37% on the amputated side could be registered. Unilateral flow reduction resp. interruption causes an asymmetric flow pattern at the aortic bifurcation. The changed hemodynamics are probably the main cause for late damage to the aorto-iliac vessels. The clinical importance of these results is that patients with unilateral leg amputation should have regular follow up investigation in order to detect late sequelae on the aorto-iliac vessels and to perform elective surgery for abdominal aortic aneurysm. Ipsilateral occlusive arterial disease as well as abdominal aortic aneurysms must be regarded as secondary late damage after leg amputation justifying obligatory indemnification. PMID- 2099172 TI - [Hearing disorders after cranial trauma]. AB - Oto-audiograms were taken from 50 patients following skull and brain injuries. 22 of them (44%) showed a deterioration of their hearing which was of traumatic origin with high probability. 10 of them (20%) had deterioration of their hearing which was most questionably caused by the trauma. Between 1 and 1 1/2 years later 19 from 22 respectively 9 from 10 patients were reexamined all together. There were 9 improvements, 5 deteriorations and 10 unchanged oto-audiograms. As many injured people do not realize a one-sided deterioration of their hearing, oto audiograms should routinely be made after head and brain injuries. The secondary deteriorations observed, demonstrate the necessity of otologic aftercare. PMID- 2099173 TI - Tight junctional inhibition of entry of Toxoplasma gondii into MDCK cells. AB - Various conditions of cultures were performed to investigate the role of tight junctions formed between adjacent MDCK cells on the entry of Toxoplasma. When MDCK cells were cocultured with excess number of Toxoplasma at the seeding density of 1 x 10(5), 3 x 10(5), and 5 x 10(5) cells/ml for 4 days, the number of intracellular parasites decreased rapidly as the host cells reached saturation density, i.e., the formation of tight junctions. When the concentration of calcium in the media (1.8 mM in general) was shifted to 5 microM that resulted in the elimination of tight junction, the penetration of Toxoplasma increased about 2-fold (p less than 0.05) in the saturated culture, while that of non-saturated culture decreased by half. Trypsin-EDTA which was treated to conquer the tight junctions of saturated culture favored the entry of Toxoplasma about 2.5-fold (p less than 0.05) compared to the non-treated, while that of non-saturated culture decreased to about one fifth. It was suggested that the tight junctions of epithelial cells play a role as a barrier for the entry of Toxoplasma and Toxoplasma penetrate into host cells through membrane structure-specific, i.e., certain kind of receptors present on the basolateral rather than apical surface of MDCK cells. PMID- 2099174 TI - [ELISA of rat sera infected with Paragonimus iloktsuenensis]. AB - Enzyme-linked immunosorbent assay (ELISA) of paragonimiasis iloktsuenensis rat sera was performed using crude antigens of Paragonimus iloktsuenensis (PIA), P. westermani (PWA) and Clonorchis sinensis (CSA). Three crude antigens (PIA, PWA, CSA) were prepared to saline homogenated supernatants of whole adult worms. Infected rat sera were obtained biweekly from the albino rats fed 50-80 metacercariae of P. iloktsuenensis through gastric catheter. Experimental groups were divided into 4 groups: GI (controls), GII, GIII and GIV according to 1-7 worms as GII, 10-19 worms as GIII and 22-40 worms as GIV, respectively. In ELISA, the mean OD values of each group for the homologous antigen (PIA) were increased significantly compared to the control sera at the 4th week of infection. With the progress of duration of infection, the mean OD values of infected sera of GII & GIV continuously increased up to the 12th week (last week), but in GIII the mean OD value increased until the 10th week. No significance was noted among the infection dose groups (GII, GIII and GIV), after the 6th week of infection. Also, the OD values of all infected rats did not show any proportional relationships to the number of worms recovered. In brief, the antibody productivity of individual rats were strongly different. The rat sera infected with P. iloktsuenensis cross reacted with those infected with P. westermani or C. sinensis, as identified by OD values. PMID- 2099175 TI - [A survey on the epidemiological factors of clonorchiasis in the Pohang industrial belt along the Hyungsan river, Kyongsangbuk-do]. AB - The employees at the Pohang industrial area, where Clonorchis sinensis has been known to be endemic along the Hyungsan River, were examined parasitologically for clonorchiasis and a part of the infected cases were surveyed with a questionnaire to outline the recent infection status of C. sinensis and epidemiological parameters in the area. Total of 3,180 cases were tested by intradermal inoculation of C. sinensis antigen (Green Cross Co., Korea), and 834 (26.2%) were found positive. Out of the positive cases, 598 were subjected to fecal examination for helminth ova. The examination revealed 129 (21.6%) ova positive cases of C. sinensis, and Trichuris trichiura 1.7%, Ascaris lumbricoides 0.3%, and Metagonimus yokogawai 0.2%. The questionnaire analysis showed some significant differences between the infected and non-infected (control) groups. The infected cases were less educated than the control, and they lived at the closer area to the river, and most of them lived there over 20 years. Also they preferred eating raw fresh water fish. Most of the detected cases were treated with praziquantel and found negative for the eggs in 85.3% of them 1 year after the treatment. The present data reveal markedly decreased endemicity of clonorchiasis compared with previous prevalence rates but still clonorchiasis is endemic in the Hyungsan river basin. A comprehensive measure including case detection, treatment and education for parasite control should be applied to control clonorchiasis in such endemic areas. PMID- 2099176 TI - [Studies on Echinostoma spp. in the Chungju Reservoir and upper streams of the Namhan River]. AB - The present study was performed to know the epidemiological status of echinostomiasis in the Chungju Reservoir and upper streams of Namhan River, together with an experimental study on the life history of Echinostoma hortense. The stool specimens of 169 inhabitants and 473 junior high school students from 5 different villages revealed 3 (0.5%) echinostomatid egg positive cases. E. hortense adult worms were recovered from one patient after a treatment and purgation. For the other two patients, it was presumed that one had E. hortense and another E. cinetorchis infection, based on the morphology of eggs. Five kinds of freshwater snails (168 Radix auricularia coreana, 534 Physa acuta, 144 Hippeutis cantori, 56 Cipangopaludina chinensis malleata and 125 Semisulcospira nodifila globus) examined for the cercariae of echinostomes showed negative results. Ten kinds of freshwater fishes examined for E. hortense metacercariae revealed positive rates as Misgurnus anguillicaudatus 40.5%, Odontobutis obscura interrupta 20.3%, Moroco oxycephalus 3.9%, and Coreoperca kawamebari 2.0%. In the experimental study, the metacercariae of E. hortense were infected to rats, eggs were collected from adult worms and cultivated, and miracidia were obtained. The miracidia were artificially infected to freshwater snails (R. auricularia), and cercarial shedding was studied. It was revealed that, when the snails were kept at a low temperature (24 degrees C), only 523 cercariae (on average) were produced during 24 hrs, while they were at a high temperature (30 degrees C), as many as 9,990 cercariae (on average) were shed during the same time. The experimental infection of E. hortense cercariae to freshwater fishes was successful in O. obscura interrupta 52.0%, M. anguillicaudatus 30.3%, C. kawamebari 27.0%, Cobitis lutheri 15.0%, M. oxycephalus 7.3%, Pseudogobio esocinus 4.3%, Squalidus coreanus 2.0%, Zacco platypus 1.3%, and Pungtungia herzi 1.3%. However, infection was not successful to snails, C. chinensis. It has been proved that the Chungju Reservoir and upper streams of Namhan river are endemic areas of echinostomiasis, especially of E. hortense, and snails such as R. auricularia coreana and fishes such as O. obscura interrupta, M. anguillicaudatus, and others are taking the role of first and second intermediate hosts, respectively. PMID- 2099177 TI - Echinostoma revolutum and Echinoparyphium recurvatum recovered from house rats in Yangyang-gun, Kangwon-do. AB - During an investigation on intestinal flukes of house rats in Yangyang-gun, Kangwon-do, a total of 6 species of trematodes belonging to 3 families; Echinostomatidae (Echinostoma hortense, E. cinetorchis, E. revolutum and Echinoparyphium recurvatum), Diplostomidae (Fibricola seoulensis) and Plagiorchiidae (Plagiorchis muris), were recovered from two adult rats. E. revolutum and E. recurvatum were new trematode faunae of rats in Korea. E. revolutum had an elongated body, 5.3-6.0 mm long and 1.0-1.3 mm wide. The total number of collar spines was 35-37 including 5 end group ones on each ventral corner. Its coiled uterus contained numerous eggs. E. recurvatum also had an elongated body, 3.5-4.7 mm long and 0.50-0.65 mm wide. It had total 45 collar spines including 4 end group ones. The uterus was short with only a few eggs. It has been first confirmed by this study that E. revolutum and E. recurvatum are indigenously distributed among house rats in Korea. PMID- 2099178 TI - [Prophylactic and therapeutic studies on intestinal giant-cystic disease of the Israel carp caused by Thelohanellus kitauei. II. Effects of physical and chemical factors on T. kitauei spores in vitro]. AB - In a basic attempt to develop the prophylactic and therapeutic measures on intestinal giant-cystic disease of the Israel carp, Cyprinus carpio nudus, the effects of physical and chemical factors on viability or survival of the spores of Thelohanellus kitauei were checked in vitro by means of extrusion test on the polar filament. When the fresh spores suspended with 0.45% and 0.9% sodium chloride solution and distilled water were laid at 5 degrees C and 28 degrees C for short terms, the extrusion rates increased until the 3rd day, meanwhile when some of them were suspended with Tyrode's solution at -70 degrees C the rates increased gradually until the 8th day. Viabilities of the spores suspended with 0.9% saline and added antibiotics to the suspension at 5 degrees C for long terms lasted for 997 days and 1,256 days (presumed values) at maximum, respectively. The spores suspended with distilled water at 28 degrees C for long terms survived 152.4 days, but the spores suspended with Tyrode's solution at -70 degrees C for long terms showed almost the same viable pattern as early freezing stages up to 780 days. The spores suspended with Tyrode's solution, frozen at -70 degrees C and thawed at 5 degrees C, showed the highest rate of extrusion of the polar filament. In the case of frozen spores, the extrusion rates during heating tend to become higher in accordance with the increase of frozen period, and the critical points of 180 day-frozen spores to be killed were generally 78.5 hr. at 60 degrees C, 23.4 hr. at 70 degrees C, 189.1 min. at 80 degrees C or 10.5 min. at 90 degrees C. The longer the spores were frozen, the more time was needed for the death of spores after thawing; 20 days-17.4 days, 100 days-33.2 days, and 400 days-37.8 days. The longer the spores were frozen, the more time was needed for the death of spores at a conventional when they were dried air drying condition, 540 days-23.5 days, 160 days-21.0 days, and 20 days-14.4 days. On the other hand, the longer the spores were frozen, the more spores were dead rapidly when they were irradiated with 10W UV-ray; 100 days-26.0 hr, 300 days-21.9 hr, and 540 days 13.9 hr. The time needed for killing 200 days-frozen spores by various disinfectants at 1,000 ppm was 5.2 min. by calcium oxide, 10.4 min. by potassium permanganate, 27.8 min. by malachite green and 14.3 hr. by formalin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2099179 TI - [Infection status of sweetfish from Kwangjung-stream and Namdae-stream in Yangyang-gun, Kangwon-do with the metacercariae of Metagonimus yokogawai]. AB - This study was performed to observe the infection status of sweetfish, caught from Kwangjung-stream and Namdae-stream in Yangyang-gun, Kangwon-do in August 1989, with the metacercariae of Metagonimus yokogawai. All of 28 sweetfish from Kwangjung-stream were infected with the metacercariae of M. yokogawai. The number of metacercariae in a fish ranged 89-521(224 on average), and the number of larvae/g of flesh was 12 approximately 55 (22 on average). On the other hand, no metacercariae were detected in the fish from Namdae-stream. It has been confirmed that the Kwangjung-stream in Yangyang-gun, Kangwon-do is one of the endemic foci of metagonimiasis in Korea. PMID- 2099180 TI - Free flow cell electrophoresis using zwitterionic buffer. AB - Studies of a zwitterionic buffer formulated for cell electrophoresis were done using the McDonnell-Douglas Continuous Flow Electrophoresis System. Standard buffers were analyzed for their stability in the electrical field and the results showed that both buffers tested were inherently unstable. Further, titration studies showed that the standards buffers buffered poorly at the pH employed for electrophoresis. The zwitterionic buffer buffered well at its nominal pH and was shown to be stable in the electrical field. Comparative studies of the buffer with standard cell separation buffers using formalin fixed rabbit and goose red blood cells showed that the zwitterionic buffer gave better resolution of the fixed cells. Studies with viable hybridoma cells showed that buffer Q supported cell viability equal to Hank's Balanced Salt Solution and that hybridoma cells in different stages of the growth cycle demonstrated reproducible differences in electrophoretic mobility. PMID- 2099181 TI - Affinity electrophoresis in agarose gels. Theory and some applications. AB - Affinity electrophoresis is the electrophoresis of components which interact during the electrophoresis procedure. Among the numerous modifications of the basic principle, affinity electrophoresis in agarose gels combined with subsequent immunochemical detection (crossed affinity immunoelectrophoresis) has emerged as a useful means of characterizing biospecific macromolecular interactions. Demonstration of ligand-binding proteins, enumeration of binding sites, evaluation of microheterogeneous forms, and estimation of binding constants can be achieved with this procedure even when analyzing small amounts of unpurified material. With an emphasis on interactions between lectins and glycoproteins as model systems, the principles and applicability of crossed affinity immunoelectrophoresis are exemplified. This includes examples of modifications developed for screening for lectins in plant extracts, for estimation of the binding capacity of affinity matrices, and for the calculation of dissociation constants. PMID- 2099182 TI - Diminished quality of two-dimensional (2-D) gel electrophoresis after freezing of the first-dimension gels. AB - Two-dimensional (2-D) gels were compared before and after freezing mini isoelectric focusing (IEF) gels in their glass tubes at -20 degrees C. Overnight storage of mini IEF gels significantly reduced the separation, resolution and number of proteins in 2-D gels. PMID- 2099183 TI - Increased migration rate observed in DNA from evidentiary material precludes the use of sample mixing to resolve forensic cases of identity. AB - The analysis of restriction fragment length polymorphisms in forensic DNA samples can be used to determine whether any two or more samples have the same biological origin. However, sometimes DNA recovered from evidentiary material, such as blood or semen stains, migrates at a different rate than an exemplar sample. This difference in migration, while maintaining the same overall pattern, produces a shift in the position of the bands. To verify that a shift in migration has occurred between evidence and exemplar samples, we have utilized two DNA probes that recognize DNA fragments that do not vary in size between individuals (monomorphic). The results obtained with this type of internal control show that differences in migration rate between exemplar and evidentiary samples can be recognized and accounted for and do not affect the ability to decide whether two patterns match. A common practice in many analytical tests, to show identity between two samples, is to test the properties of the samples individually and mixed. However, this approach is not applicable to all forensic DNA identity tests. In many cases, DNA from forensic samples may be irreversibly modified and this can alter the migration rate of the DNA samples. Thus, in a mixture of DNA from exemplar and evidence, the same polymorphic DNA fragments may not comigrate and produce a composite pattern which could lead to false exclusions. PMID- 2099184 TI - Development of a high-performance electrophoretic light scattering apparatus for mobility determination of particles with their Stokes' radii of several nanometers. AB - A sophisticated electrophoretic light scattering apparatus was developed. It allows reliable measurements of electrophoretic mobilities of charged macromolecules, such as proteins, nucleic acids and synthetic polyelectrolytes which have been out of the range of the apparatuses of this type aimed at relatively large particles such as microspheres and biological cells. The present apparatus features the monitoring of the electroosmotic flow profile and the determination of the sign of the electrophoretic mobility of an object as well as its high-performance based on the improvement in various facets of acquisition and handling of the signals and data. PMID- 2099185 TI - Synthesis and characterization of gentiobiose heptaacetate conjugate vaccines that produce endotoxin-neutralizing antibodies. AB - We have prepared aminoethyl (AE), aminopropyl (AP), and aminopentyl (APT) derivatives of gentiobiose heptaacetate (GH). These spacer compounds (AEGH, APGH, APTGH) have been coupled to succinylated diphtheria toxoid (Suc.DT) to produce conjugate vaccines. These conjugates all bind to the anti-lipid A human monoclonal antibody A6(H4C5) in an ELISA binding assay. Rabbits immunized with the APGH conjugate vaccine in either Freund's complete adjuvant or aluminum hydroxide gel produced antibody levels of 5120 and 3600 ELISA units, respectively, compared to an antibody level of less than 20 ELISA units for the prebleed sera. Sera from mice immunized with either the aminopropyl or the aminopentyl conjugate had antibody levels of 5120 and 2560 ELISA antibody units, respectively. These antibodies neutralized endotoxin in a Limulus lysate neutralization assay. Protection against the local Shwartzman reaction was demonstrated (p less than 0.05) in eight out of nine rabbits immunized with the Suc-DT-APGH conjugate vaccine compared to three out of 10 rabbits immunized with the carrier protein Suc-DT. Passive transfer experiments demonstrated that four out of five rabbits receiving immune serum were protected from Shwartzman reaction compared to one out of five rabbits receiving normal serum (p less than 0.1). These results indicated that epitopes contained in gentiobiose heptaacetate when properly presented as conjugate vaccines were capable of inducing neutralizing antibodies against endotoxin. PMID- 2099186 TI - Substituted 2-iminothiolanes: reagents for the preparation of disulfide cross linked conjugates with increased stability. AB - Much attention has been focused recently on the stability of immunotoxin (antibody-toxin) conjugates linked by a disulfide bridge. Conflicting reports have appeared regarding the in vivo stability of such conjugates prepared with the two most commonly used cross-linking reagents, SPDP and 2-iminothiolane. We have developed (i) a series of reagents based on 2-iminothiolane substituted at the 4- and/or 5-positions (X2ITs) which, based on model studies with simple amines, should show enhanced disulfide stability when conjugated with antibodies or other proteins and (ii) a real-time method for monitoring the rate and extent of conjugation of these reagents with amino groups. Depending upon the substituent, the stability of model-activated disulfides relative to unsubstituted 2-iminothiolane was increased from 5- to 4000-fold as measured by glutathione-induced release of thionitrobenzoic acid. This family of cross linking reagents should allow the construction of disulfide cross-linked toxin, drug, or enzyme conjugates with enhanced stability in vivo. PMID- 2099187 TI - Radioiodination of antibodies via N-succinimidyl 2,4-dimethoxy-3 (trialkylstannyl)benzoates. AB - We have previously shown that use of N-succinimidyl 3-iodobenzoate (SIB) for radioiodination of monoclonal antibodies (MAbs) decreases the loss of radioiodine in vivo compared to MAbs labeled by using conventional methods. Herein, the synthesis of N-succinimidyl 2,4-dimethoxy-3-(trialkylstannyl)benzoates (alkyl = Me, Bu) are described as is their use as precursors for the radiosynthesis of N succinimidyl 2,4-dimethoxy-3-iodobenzoate (SDMIB). A MAb F(ab')2 fragment labeled with SDMIB retained its ability to bind specifically to tumor homogenates. Paired label tissue distribution studies indicate that the thyroid uptake (an indicator of deiodination) of hydrolyzed SDMIB was about 20 times that of hydrolyzed SIB. In contrast, thyroid uptake for SDMIB, when conjugated to a MAb, was only 1.4-2.8 times that for SIB and was considerably lower than levels reported in the literature for MAbs labeled by using direct, electrophilic iodination methods. Although MAbs labeled with SDMIB are significantly more inert to dehalogenation than those labeled by conventional methods, compared to the original SIB reagent, addition of two methoxy groups decreased retention of label in vivo. PMID- 2099188 TI - Carrier design: biodistribution of branched polypeptides with a poly(L-lysine) backbone. AB - The biodistribution has been examined in mice of a range of synthetic branched polypeptides which are based on a polylysine backbone but which differ in ionic charge, side-chain structure, and molecular size. Polycationic polypeptides, regardless of their size or primary structure at the branches, were cleared rapidly from the circulation, the liver being the major site of clearance. Polypeptides with glutamic acid in the side chain, which would be amphoteric under physiological conditions, showed a significantly prolonged blood survival, and this was seen with polypeptides in the range of molecular weights of 46,000 up to 213,000. Such polypeptides provide a useful system with which to investigate the effect of structural parameters on the pharmacokinetic properties of carrier molecules and would allow the selection of candidate carriers for a variety of uses. PMID- 2099189 TI - Enhanced kidney clearance with an ester-linked 99mTc-radiolabeled antibody Fab' chelator conjugate. AB - Bifunctional chelators for labeling antibodies with 99mTc based on the N3S core of (mercaptoacetyl)-triglycine having ester or amide linking moieties were synthesized and site-specifically attached to the sulfhydryl groups of the Fab' fragment of antimyosin. Protein labeling was quantitative after 15 min; postlabeling purification was not necessary. The radiolabeled conjugates exhibited no loss of immunoreactivity. Under basic conditions, the ester-linked conjugate lost 95% of the radiolabel in the form of the 99mTc complex of (mercaptoacetyl)triglycine as determined by RP-HPLC, while the radioactivity in the amide-linked conjugate remained completely bound to the protein. In a mouse biodistribution study, the ester-linked conjugate showed a 2-fold enhancement in clearance from the kidney when compared to the amide-linked product. PMID- 2099190 TI - CDC36 and CDC39 are negative elements in the signal transduction pathway of yeast. AB - Mutations in either the CDC36 or CDC39 gene cause yeast cells to arrest in G1 of the cell cycle at the same point as treatment with mating pheromone. We demonstrate here that strains harboring temperature-sensitive mutations in CDC36 or CDC39 activate expression of the pheromone-inducible gene FUS1 when shifted to nonpermissive temperature. We show further that cell-cycle arrest and induction of FUS1 are dependent on known components of the mating factor response pathway, the STE genes. Thus, the G1-arrest phenotype of cdc36 and cdc39 mutants results from activation of the mating factor response pathway. The CDC36 and CDC39 gene products behave formally as negative elements in the response pathway: they are required to block response in the absence of pheromone. Epistasis analysis of mutants defective in CDC36 or CDC39 and different STE genes demonstrates that activation requires the response pathway G protein and suggests that CDC36 and CDC39 products may control synthesis or function of the G alpha subunit. PMID- 2099193 TI - Short-term prediction of HIV infection and AIDS: a critique of the Working Group's Report to the Department of Health. AB - The Report of the Working Group on the Short-Term Prediction of AIDS/HIV (the Cox Report) is reviewed mainly to assess its calculations of the numbers of people in England and Wales who are infected with the human immunodeficiency virus (HIV). Two main methods are used in the report to estimate this total--the direct method and the back projection method. The direct method estimates the number of people infected with HIV by attempting to specify the numbers of people in various at risk groups, and the percentage infected in those groups. Of particular significance are the estimates given for male homosexuals. The Cox Report suggests that between 4.0% and 4.7% of the male population aged between 16 and 59 are homosexual, and that between 1.9% and 4.5% of these are HIV antibody positive. The basis on which these estimates are made is not substantiated by the Report, and it is quite possible that the upper limit given for HIV prevalence in male homosexuals represents an understatement of the actual number by a factor of 2.5 or more. The back projection method estimates HIV prevalence from the numbers of cases of the acquired immunodeficiency syndrome (AIDS) and the incubation function, the relationship between HIV infection and the probabilities of AIDS in each of the years following infection. Using this method the Cox Report fails to produce results that are in accordance with our knowledge of how the epidemic developed during the 1980s. As a consequence of this the various calculations of numbers of HIV antibody-positives to 1987 given in the Cox Report are all almost certainly underestimates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099191 TI - Membrane traffic between secretory compartments is differentially affected during mitosis. AB - Membrane traffic has been shown to be regulated during cell division. In particular, with the use of viral membrane proteins as markers, endoplasmic reticulum (ER)-to-Golgi transport in mitotic cells has been shown to be essentially blocked. However, the effect of mitosis on other steps in the secretory pathway is less clear, because an early block makes examination of following steps difficult. Here, we report studies on the functional characteristics of secretory pathways in mitotic mammalian tissue culture cells by the use of a variety of markers. Chinese hamster ovary cells were transfected with cDNAs encoding secretory proteins. Consistent with earlier results following viral membrane proteins, we found that the overall secretory pathway is nonfunctional in mitotic cells, and a major block to secretion is at the step between ER and Golgi: the overall rate of secretion of human growth hormone is reduced at least 10-fold in mitotic cells, and export of truncated vesicular stomatitis virus G protein from the ER is inhibited to about the same extent, as judged by acquisition of endoglycosidase H resistance. To ascertain the integrity of transport from the trans-Golgi to plasma membrane, we followed the secretion of sulfated glycosaminoglycan (GAG) chains, which are synthesized in the Golgi and thus are not subject to the earlier ER-to-Golgi block. GAG chains are valid markers for the pathway taken by constitutive secretory proteins; both protein secretion and GAG chain secretion are sensitive to treatment with n-ethyl maleimide and monensin and are blocked at 19 degrees C. We found that the extent of GAG-chain secretion is not altered during mitosis, although the initial rate of secretion is reduced about twofold in mitotic compared with interphase cells. Thus, during mitosis, transport from the trans-Golgi to plasma membrane is much less hindered than ER-to-Golgi traffic. We conclude that transport steps are not affected to the same extent during mitosis. PMID- 2099194 TI - Genivir (DIP-253) 1% cream versus placebo cream in the treatment of recurrent genital herpes: a double-blind study. AB - A total of 100 heterosexual adults of either sex with frequent episodes of recurrent genital herpes were allocated to treatment with either Genivir (DIP 253) 1% cream or placebo cream. All patients had genital herpes previously verified by a positive viral culture. The study was carried out as a double-blind parallel group trial. Fifty patients were allocated to each of the two treatment groups. The treatment was initiated within 24 hours after the first sign of a recurrence, and at the pretreatment examination all patients had developed typical lesions with blisters and/or sores. At baseline a sample for herpes virus culture and typing was obtained. The creams were applied four times daily for five days. Follow-up examinations were carried out on days 1, 2, 4 and if needed on days 7, 10 and 14. The major factor used for assessment of efficacy was the time to complete healing of all lesions. Duration of pruritus and pain were also recorded. In the group of patients treated with Genivir cream the time to complete healing was 3.3 days and in the placebo group 6.1 days. The difference was statistically significant (P less than 0.001). The mean duration of pain was 1.3 days in the Genivir group and 2.5 days in the placebo group: this difference also reached significance (P less than 0.01). The duration of pruritus was about the same in both groups. The active agent in Genivir, DIP-253, is a heterocyclic aromatic complex with confirmed anti-herpetic activity and with evidence of a local immunomodulatory effect. It was concluded that the efficacy of topical application of DIP-253 may be due to combined antiviral and immunomodulatory activities. PMID- 2099195 TI - Genitourinary medicine and sexually transmitted diseases in the 1990s. PMID- 2099192 TI - Heparin inhibits c-fos and c-myc mRNA expression in vascular smooth muscle cells. AB - Heparin is a potent inhibitor of vascular smooth muscle cell (VSMC) growth. In this paper we show that heparin suppressed the induction of c-fos and c-myc mRNA in rat and calf VSMC. This effect of heparin is closely associated with its growth-inhibitory activity, as shown by isolating and characterizing a strain of rat VSMC that was resistant to heparin's antiproliferative effect; heparin did not suppress c-fos mRNA induction in these cells. Moreover, neither a nonantiproliferative heparin fragment or other glycosaminoglycans that lack growth-inhibitory activity repressed c-fos or c-myc mRNA levels. The effect of heparin on c-fos mRNA induction was selective for specific mitogens, as heparin inhibited c-fos mRNA induction in phorbol 12-myristate 13-acetate (TPA) stimulated but not epidermal growth factor (EGF) stimulated VSMC. The effect of heparin on gene expression is independent of ongoing protein synthesis, and inhibition of c-fos mRNA is at the transcriptional level. These results suggest that heparin may selectively inhibit a protein kinase C-dependent pathway for protooncogene induction and that this may be one mechanism used by heparin to inhibit cell proliferation. PMID- 2099196 TI - HIV infection in sexually transmissible disease practice in Sydney: the effects of legislation, public education and changing clinical spectrum. AB - The experience with human immunodeficiency virus (HIV) infection of a private inner-city sexually transmissible diseases (STD) clinic in Sydney was quantified. Between February 1984 and March 1988, 2073 of the Clinic's patients were tested for antibodies to HIV on 5095 occasions. Of those tested, 538 (26%) were positive for antibodies to HIV: 532 (98.9%) of the seropositives had practised male homosexual intercourse. This is the highest reported seroprevalence of HIV for any primary care service in Australia. Those individuals seropositive because of other risk behaviours were detected by voluntary contact tracing rather than by screening. Female prostitution was not found to be a risk factor for HIV. In general, rates of first HIV antibody tests were adversely affected by threatening legislation, and temporarily stimulated (among lower-risk persons) by a national television campaign. These data suggest that much of the counselling, detection and management of HIV infection in Australia is occurring in private practice, and that STD services (private and public) are at the forefront of the HIV epidemic. This has implications for disease surveillance and control, health services planning and medical education. PMID- 2099197 TI - Efficacy of combined metronidazole and triple tetracycline therapy in the treatment of non-gonococcal urethritis. AB - In a double-blind placebo-controlled trial using triple tetracycline (Deteclo, Lederle) 300 mg twice daily for two weeks in conjunction with metronidazole (Flagyl, May & Baker) 400 mg or matching placebo twice daily for seven days, it was shown that the addition of anti-anaerobic therapy did not significantly affect the number of cases of persistent urethritis or the relapse of patients with non-gonococcal urethritis (NGU). PMID- 2099198 TI - Potential risks of ultraviolet radiation in HIV infection. AB - The hazards of ultraviolet radiation (UVR) include immunosuppression, activation of human immunodeficiency virus (HIV) type 1 expression, and photocarcinogenesis particularly in immunosuppressed individuals. Fifty-eight male homosexuals positive for HIV antibody and 61 controls not at risk for HIV infection answered a questionnaire on their attitudes and exposure to natural and artificial sources of UVR. Controls were matched for sex but were not from an at-risk group for HIV infection. Mean ages were similar for both groups. HIV seropositives had greater recreational UVR exposure than controls: 12/58 versus 4/61 had regular use of a sunbed (P less than 0.05), and experienced 11.6 weeks versus 9.5 weeks of prolonged natural UVR exposure (P = 0.056) over a four-year period. One reason for this difference may be the misconception present in two-thirds of the HIV seropositive group that a suntan would improve their health and the outcome of their HIV infection. Those with HIV infection must be made aware that there is a potential for further immunosuppression and viral activation from UVR and they should be advised to avoid undue recreational exposure. PMID- 2099199 TI - Evaluation of an enzyme immunoassay for detection of Chlamydia trachomatis in urogenital specimens. AB - Chlamydiazyme (Abbott), an enzyme-linked immunoassay (EIA), was evaluated using cell culture on Hela 229 cells as the method of reference. Samples were acquired from 611 female and 280 male patients attending the outpatient clinic for sexually transmitted disease at the University Hospital in Rotterdam, The Netherlands. The prevalences of chlamydia culture-positive female and male patients were 7.8% and 14.4% respectively. The overall sensitivity and specificity values of the EIA were respectively 68.1% and 95.8% in the female and 92.1% and 92.0% in the male population. Samples which were culture-negative but EIA-positive were re-examined by a second direct test (IDEA; Boots Celltech). If the samples from 12 females and 11 males which were negative on culture but positive with both direct tests are considered as failures of cell culture, the sensitivity of the EIA in females almost equalled cell culture (74.6% versus 79.9%) and in males was even higher (93.9% versus 77.6%). Serotyping of the cultured strains revealed that all serovars of Chlamydia trachomatis occurring in this study could be detected by the EIA. The EIA offers a relatively simple and rapid test for diagnosis of C. trachomatis infections in high-risk populations. PMID- 2099200 TI - Serological evidence for human immunodeficiency virus type 2 in east Africa. AB - Infection by human immunodeficiency virus type 2 (HIV-2) has not previously been described in North or East Africa. We examined over 1200 sera of high-risk individuals from three North/East African countries for antibodies to HIV-2. Results indicated that 17 were repeatedly reactive by ELISA; 4 were confirmed by Western blot. Of the 4 confirmed, 2 produced strong reactions to the envelope antigens of HIV-2 but not of HIV-1. One of these subjects was a foreigner from Senegal who was tested while in Egypt and one was a Djiboutian prostitute who was infected presumably prior to October 1987. We conclude that HIV-2 has been introduced into this region and that specific testing of selected individuals for HIV-2 is warranted. PMID- 2099201 TI - Myelodysplastic syndrome occurring as possible first manifestation of human immunodeficiency virus infection with subsequent progression to aplastic anaemia. PMID- 2099202 TI - Notes on the Medical Society for the Study of Venereal Diseases (MSSVD), 1952 1989. PMID- 2099203 TI - AIDS Literature Index. PMID- 2099204 TI - Mental health programs for American Indians: their logic, structure and function. PMID- 2099205 TI - Macroscopical and microscopical anatomy of the hippocampus in the dog. AB - In this article we have studied the topography, relationship and projection of the hippocampus in the dog by means of 1 mm thick transverse, horizontal and parasagital sections stained with Mulligan's reagent and 50 microns transverse sections (Nissl). The macroscopical disposition of this part of the CNS was completed by means of a gross dissection. Horizontal sections of 10 microns through the middle or limbic part were used to determine the general microscopic anatomy and to define the morphometry of its cells. From this point of view the Hippocampus of the dog appears to be intermediate between the rat and primates, species better studied. PMID- 2099207 TI - Microbiological features of stable osseointegrated implants used as abutments for overdentures. AB - The microflora associated with osseointegrated implants used as abutments for overdentures was investigated in 18 edentulous patients, 2 years after implantation. 52.8% of the organisms cultured were facultatively anaerobic cocci and 17.4% were facultatively anaerobic rods, while Gram-negative anaerobic rods accounted for only 7.3%. Fusobacterium sp. and Bacteroides intermedius were both found in 8.8% of the samples. B. gingivalis and spirochetes were not found. Repeated microbiological and clinical data were collected in 9 patients during the 3rd, 4th and 5th year after implantation. No significant time trends were noted. Separate samples taken within the same patient from different sites were similar. Therefore, bacteriological independence of sites could not be assumed for the conditions investigated. PMID- 2099206 TI - Effects of training on fibre composition in rat gastrocnemius muscle. AB - Forty-eight adult Wistar rats were divided into four groups for experimentation. The group I was used as a control and groups II, III and IV underwent progressive treadmill training. Samples of the red and mixed portions of m. gastrocnemius (lateral head) were stained with the histochemical technique of m-ATPase to determine the percentage of type I, IIA and IIB fibres, and with NADH-TR, in order to quantify variations in "low-oxidative" fibre percentages. The results showed that progressive training did not lead to statistical variations in the percentage of type I fibres. However, the proportion of type IIA fibres rose, while that of IIB fibres fell, in both cases significantly. Variations were more marked in mixed than in red Gastrocnemius muscle. A clear decrease was noted in "low-oxidative" fibres, which were virtually absent from red portion. This decrease was more marked, and occurred more rapidly, than in type IIB fibres. PMID- 2099208 TI - Histology of tissues surrounding single crystal sapphire endosseous dental implants: an experimental study in the beagle dog. AB - 9 single crystal sapphire dental implants were installed bilaterally into pre extracted areas in the lower jaw of two beagle dogs and histologically analysed after 180 days in situ. 8 implants were stable and radiographs disclosed complete bone healing. Light-, scanning- and transmission electron microscopy demonstrated that the stable implants were surrounded by a mineralizing bone boundary and a mucosa nearly free from inflammatory cell infiltrations. The 9th implant was mobile and surrounded by a non-mineralized connective tissue capsule containing bundles of collagen. The ultrastructure of the mucosa surrounding the implants closely resembled the mucosa surrounding the tooth. Histometric analysis of the alveolar bone surrounding the stable implants revealed that the value of the bone contact surface ranged from 37.1% to 86.9% (mean value 61.8%) at the light microscopic level. PMID- 2099209 TI - Regeneration and enlargement of jaw bone using guided tissue regeneration. AB - The purpose of this study was to present the surgical procedures and the clinical results of guided tissue regeneration (GTR) treatment aimed at regenerating local jaw bone in situations where the anatomy of the ridge did not allow the placement of dental implants. 12 patients were selected for ridge enlargement or bony defect regeneration. A combined split- and full-thickness flap was raised in areas designated for subsequent implant placement. Following perforation of the cortical bone to create a bleeding bone surface, a PTFE membrane was adjusted to the surgical site in such a way that a secluded space was created between the membrane and the subjacent bone surface in order to increase the width of the ridge or to regenerate bony defects present. Complete tension-free closure of the soft tissue flap was emphasized. Following a healing period of 6 to 10 months, reopening procedures were performed and the gain of bone dimension was assessed. In 9 patients with 12 potential implant sites, a sufficient bone volume was obtained to allow subsequent implant placement. The gain of new bone formation varied between 1.5 and 5.5 mm. In 3 patients, acute infections developed which necessitated early removal of the membranes and no bone regeneration could be achieved. The results of the study indicate that the biological principle of GTR is highly predictable for ridge enlargement or defect regeneration under the prerequisite of a complication-free healing. PMID- 2099210 TI - Tissue integration of non-submerged implants. 1-year results of a prospective study with 100 ITI hollow-cylinder and hollow-screw implants. AB - It has been postulated that the wound healing in a closed submerged location is one of the prerequisites for osseointegration of dental implants. The purpose of the present study was to evaluate the tissue integration of intentionally non submerged titanium implants inserted by a one-stage surgical procedure. 100 ITI implants were consecutively placed in 70 partially edentulous patients. After a healing period free of masticatory loading for at least 3 months, the implants were examined. The clinical status showed for all implants neither detectable mobility nor signs of a peri-implant infection. Therefore, prosthetic abutments were inserted, and the patients were restored with fixed partial dentures. All patients were regularly recalled at 3-month intervals, and no patient dropped out of the study. Thus, all 100 implants were re-evaluated 12 months following implantation. Plaque- and sulcus bleeding indices, probing depth, clinical attachment level, width of keratinized mucosa, and periotest scores were assessed. In addition, standardized radiographs were analyzed for the presence of peri-implant radiolucencies and for the location of alveolar bone levels around the implants. Based on predefined criteria, the implants were classified as successful or failing. 98 implants were considered successful, and 1 implant failing. The remaining implant exhibited a peri-implant infection requiring local and systemic antimicrobial treatment. The results of this short-term study indicate that intentionally non-submerged ITI implants yield a high predictability for successful tissue integration. PMID- 2099211 TI - Fixed reconstructions in partially edentulous patients using two-part ITI implants (Bonefit) as abutments. AB - Fixed reconstructions on implant abutments may be a welcome modality in the treatment of partially edentulous patients following the principles of a prophylactically oriented comprehensive care. The option to create artificial tissue integrated abutments widens the range of indications for fixed reconstructions. Risky long-span bridges as well as the preparation of intact teeth for bridge abutments may frequently be avoided. Never should the contours of the prosthesis interfere with the patient's performance of optimal plaque control. Furthermore, supportive periodontal therapy with regular maintenance visits must be provided to optimize a long-term prognosis of the dention as well as the tissue-integrated artificial abutments. PMID- 2099212 TI - Distribution of bacterial morphotypes around natural teeth and titanium implants ad modum Branemark. AB - The subgingival plaque around both teeth and implants was analysed by means of differential phase-contrast microscopy. It was noted that, in comparison to natural teeth, the subgingival samples from implants were more frequently too small to provide adequate bacterial counts. In 24 partially edentulous patients (with implants and teeth in the same jaw), no significant differences in the distribution of bacterial morphotypes could be found between implants and natural teeth. The %s of coccoid cells, motile rods, spirochetes and other bacteria were 65.8, 2.3, 2.1, and 29.8 for implants and 55.6, 4.9, 3.6, and 34.9 for teeth, respectively. However, when the plaque composition on the implants of fully edentulous patients was compared with those of teeth or implants of partially edentulous patients (with teeth and implants in the same and/or opposite jaw), significant differences appeared. In fully edentulous patients, more coccoid cells (71.3%) and significant fewer motile rods (0.4%) and spirochetes (0.0) were found around the implants. The results suggest that teeth may serve as a reservoir for the bacterial colonisation of titanium implants in the same mouth. PMID- 2099213 TI - The development of a central register for side effects of biomaterials. AB - Examination of the interaction between biomaterials and tissues from a clinical realistic as well as scientific viewpoint to complement the highly advanced experimental and biochemical basis research is an undertaking that has suffered a considerable amount of neglect in the past. Attempts to realize internationally a Central Registry for documenting clinically relevant side effects will be reported in detail. Implementation of the registry involves the review of present literature (prospective clinical studies, retrospective studies and case reports). An "incompatibility incident report/questionnaire" has been developed according to the guidelines of the "Report on Pharmacological Side Effects" of the Pharmaceutical Commission of the German Medical Association. The aims of registering and evaluating these reports will be demonstrated and discussed in detail. PMID- 2099214 TI - Cell adhesion to the surfaces of polymeric beads. AB - The main goal of this study is to determine the relationship between the surface properties of polymeric materials and fibroblastic cell adhesion. Therefore, two series of polymeric beads, PHEMA and PS, were tested in microcarrier-facilitated cell culture systems. The crosslinked PHEMA beads were prepared by suspension polymerization of HEMA monomer in the presence of various acrylic monomers (i.e. MMA, EGDMA, DMAEMA). The hydrophobic PS beads were used after coated with different alkylamine monomers (i.e. EDA, ALAM, TEA) by plasma polymerization process. The cell culturing studies were performed with BHK cells in stationary culture conditions and the cell adhesion characteristics were determined by the common methods. Attachment of the BHK cells on these microcarriers were satisfactorily modeled by surface saturation type of mathematical expression. The results demonstrated that, there were finite number of sites on the microcarrier surfaces available for adhesion. Number of these sites depends on the surface charge density which was supplied by amine groups and surface wettability. It is possible to achieve desired cell adhesion and also growth, by changing the chemical structure of beads with suitable modification methods. PMID- 2099215 TI - Rapid adsorption of rheumatoid factor (RF) on suspension of glutaraldehyde crosslinked immunoglobulin G (IgG)--a method to avoid RF interference. PMID- 2099216 TI - Long-term plasma exchange via Cimino fistula in patients with hypercholesterolemia. AB - Two patients with familial hypercholesterolemia were treated by long-term plasma exchange via an arteriovenous Cimino shunt using unselective membrane separation. Cholesterol was lowered to 40 percent (+/-3) of peak levels by each procedure. Sieving coefficient was 0.76 (+/-0.12). With a mean exchange interval of 11 days (+/-2), the peak cholesterol levels decreased from 406 mg per dl (+/-28) to 322 mg per dl (+/-27), the LDL fraction from 338 mg per dl (+/-9) to 265 mg per dl (+/-25) whereas the HDL fraction remained unchanged at 28 mg per dl (+/-4). Electrocardiographic stress testing improved in the first patient after treatment for 12 months. PMID- 2099217 TI - Immunosorbents for LDL-apheresis. AB - Low density lipoprotein (LDL) (1,03-1,05 g/ml) was utilized as antigen to obtain polyclonal (PcAb) and monoclonal (McAb) antibodies. Immunosorbents capable of selective removing LDL from human plasma were developed on the basis of the antibodies preparation. The sorbents called "Immunoliposorber PcAb" and "Immunoliposorber McAb" are currently undergoing clinical trials in the USSR Cardiology Research Center, Acad. of Med. Sciences. PMID- 2099218 TI - Heparin-sorbent for low density lipoproteins removal in hypercholesterolemia. AB - Heparin-sorbent was developed in the USSR Cardiology Research Center for LDL apheresis in patients with familial hypercholesterolemia. Clinical trials of the sorbent were started in 1985. Heparin-sorbent has a high capacity for LDL. One column (400ml) can remove 3 - 6g of LDL cholesterol, depending on the initial LDL content in the plasma. The sorbent demonstrates a high stability, it can withstand more then 75 sorbtion-desorbtion cycles with only a slight loss of the initial capacity. It means that one column can work for 1,5-2,0 years when used weekly. Heparin-sorbent is the sorbent of limited selectivity, apo-B content in eluate is 40-60% of the total protein content, but it is important that it does not bind HDL. PMID- 2099219 TI - Computerized microscopic image analysis method in tissue-biomaterials interaction. AB - The use of computer-based image analysis belongs to the new methods of biocompatibility testing. When materials were implanted subcutaneously in animals the cells of the connective tissue capsule can give a good standard for the evaluation of biocompatibility. The application of image processing systems allows the automation of a great number of measurings and test - techniques. It is also possible to get quantitative information on cell - and haemocompatibility testing. With the help of the automatic microscopic image analysis the accuracy of morphometric methods increased and scientists time was saved. PMID- 2099220 TI - Towards an artificial cornea: surface modifications of optically clear, oxygen permeable soft contact lens materials by ammonia plasma modification technique for the enhanced attachment and growth of corneal epithelial cells. AB - The advent of high water content, oxygen permeable contact lens materials has made the intracorneal implants more feasible. A major obstacle encountered is the regrowth of a stable epithelium over the implant. Therefore, ammonia gaseous plasma modification technique was used to modify the surface chemical properties of soft contact lens material such as poly(2-hydroxyethyl methacrylate and methacrylic acid), PHEMA-MAA copolymer, in an attempt to enhance the cell attachment and growth of rabbit corneal epithelial cells. PMID- 2099221 TI - Binding of C1q and DNA to support materials by means of a new coupling procedure. AB - Since several years matrix-bound biologically active substances are widely used in biosciences, biotechnology and medicine. We are presenting a simple and inexpensive activation procedure for support materials which allows stable binding of C1q and DNA. We could not found a remarkable leakage of the bound ligands. In connection with the good biocompatibility of our procedure, both are important for the application in extracorporeal immunoadsorption. The method is technologically simple and represents an alternative to the activation methods applied so far. PMID- 2099223 TI - Immunosorbents based on uncoated synthetic charcoals: preparation, properties, applications. AB - By means of water-soluble carbodiimide coupling technique various bioligands were covalently attached to the surface of uncoated synthetic active carbons and a number of sorbents with certain biological functions were thus designed. Carbonaceous sorbents with immobilized ligands demonstrate increased affinity towards specific sorbates compared to that of starting matrix. As soon as SCN and SCS synthetic carbons are used uncoated they can be highly loaded with protein molecules - up to 80 mg serum albumin, 6-10 mg IgG rabbit etc. per gram of sorbent. Carbonaceous immunosorbents retain biocompatibility and substantial non specific adsorptive capacity of initial hemosorbents. A conclusion is drawn that uncoated synthetic charcoals can serve a basis for design of selective hemosorbents intended for solving complicated problems of immunocorrection. PMID- 2099222 TI - Biospecific adsorbents on the basis of chloroformate-activated bead cellulose. AB - Carbohydrate-derived polymers are activated by the chloroformate N chlorocarbonyloxy-5-norbornene-2.3-dicarboximide (ClCOONB). The advantages of this activation method are presented. The application of bead cellulose as adsorbent for biomedical and biotechnological purposes is demonstrated. Examples for immunoglobulin purification, streptavidin isolation, and biotransformation of porcine insulin are given. PMID- 2099224 TI - Development of a DNA-adsorbent for the specific removal of anti-DNA autoantibodies in systemic lupus erythematosus (SLE). AB - Autoantibodies against DNA are of primary importance for the diagnosis and pathogenesis of systemic lupus erythematousus (SLE). The level of anti-DNA antibodies correlates well with the disease activity and renal involvement. In such patients the removal of anti-DNA antibodies from plasma may lead to a clinical improvement. For this reason an adsorbent was made by covalent coupling of calf thymus DNA to a solid support based on ethylene dimethacrylate cross linked hydroxethyl methacrylate. Up to 2.5 mg of DNA were immobolized to 1 ml of the support activated chemically by aminosilane and glutaraldehyde. The incubation of 40 ml of SLE plasma with 1 ml of the adsorbent resulted in a 50% decline in anti-DNA activity. There was no release of immobilized P-32-DNA into the plasma. Biocompatibility, sterilisation, and reapplication (without loss of binding capacity) of the adsorbent could be demonstrated. We concluded that the adsorbent may be suitable for treatment. PMID- 2099226 TI - A screening test for modified hemoglobin blood substitutes before clinical use: based on C3a complement activation in human plasma. AB - Modified hemoglobin preparations may potentially cause hypersensitivity and anaphylactic reactions, antibody-antigen reactions and other problems. Unfortunately response in animal safety studies may not reflect the same response in human. The next best test before clinical trial in human may the use of human plasma in-vitro. This paper present an in-vitro procedure based on complement activation (C3a) of human plasma. The procedure involves collecting heparinised blood and separating the plasma and freezing the heparinised plasma at -70 degrees C until use. Each 100 lambda of control or test samples is added to 400 lambda of this plasma. This is incubated at 37 degrees C, 60 rpm for 1 hour, then added to EDTA saline to stop the reaction and stored at -70 degrees C until analysed by standard radioimmunoassay for C3a. (C3 measurement is not sensitivity enough). Using the screening test procedure described above, C3a levels (ng/ml) in plasma were: control, 1,980 +/- 280; Zymosan, 20,000; Hemoglobin preparation A, 2,227 +/- 617; Hemoglobin preparation B, 4,967 +/- 153; A 75% + B 25%, 3,967 +/- 270; A 50% + B 50%, 4,553 +/- 517; A 25% + B 75%, 4,920 +/- 430. Hemoglobin preparation A did not cause significant increases in C3a complement activation. Hemoglobin preparation B caused significant increase in C3a complement activation. Serial dilution of Hemoglobin preparation B in Hemoglobin preparation A continued to cause the same degree of C3a complement activation. This is not due to C3 exhaustion because Zymosan resulted in C3a of greater than 20,000ng/ml. This appears to show that this screening test can detect complement activation even at low concentrations of the hemoglobin preparation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099227 TI - [Current status of research of a lymphatic system in the nervous system: initial trials with cerebral lymphography]. AB - After having recognized the existence of post-mortem intra-cerebral circulation of a coloring substance with lymphatic resorption, the author is continuing his research by injecting a product sharing the same characteristics: Iotrolan. Brain X-rays show brain circulation from the cortex to the ventricular cavities and from the spinal cord to the bulbar area and to the cerebellum. One question deserves to be asked: what is this circulation? PMID- 2099225 TI - Hemodialysis-hemoperfusion in fulminant viral hepatitis. AB - It is theorized that charcoal hemoperfusion and hemodialysis with a highly permeable membrane should be synergistic in the management of fulminant hepatic failure. Previous studies have shown marked differences between these two treatments in their effects in the various biochemical abnormalities of this serious clinical problem. Survival rates in patients treated with charcoal hemoperfusion approximate the rates in those treated with hemodialysis with a highly permeable membrane but are only slightly better than in untreated cases. The excellent recovery of two patients with fulminant viral hepatitis in stage III and IV coma treated with this combined regimen indicates that further studies should be done to confirm this thesis. PMID- 2099228 TI - [Neurophysins]. AB - Neurophysins are neuropeptides (MW +/- 10,000) synthetized together with active nonapeptides vasopressin (AVP) and oxytocin (OT). The original description of the radioimmunoassay for neurophysins in 1969 allowed us to demonstrate the concomitant, equimolecular, release of them together with AVP and OT, thus bringing strong arguments in favour of neurohypophyseal exocytosis. Beside the use of those RIAs as direct indexes of neurohypophyseal release in various physiological and pathological conditions, we have been interested these last two years, to the putative use of neurophysins RIA as direct neuroendocrine markers in various neuropsychiatric diseases (depression, mania, schizophrenia) and paraneoplastic syndromes (SIADH). PMID- 2099229 TI - [Excess of thiocyanate and selenium deficiency: cofactors in the etiology of endemic goiter and cretinism in North Zaire]. AB - Endemic goitre is accompanied by a spectrum of iodine deficiency disorders (IDD). From work undertaken by CEMUBAC in Ubangui Zaire, the role of thiocyanate overload is recalled while this work demonstrates for the first time in man an action of selenium supplementation (and thus deficiency) on thyroid function in iodine deficient areas. The extreme severity of the selenium deficiency may intervene either on the central and/or peripheral deiodination of thyroxine, or on the synthesis of the thyroid hormones. Together with thiocyanate overload, selenium deficiency may be responsible of the high frequency of myxedematous cretins in Zaire. PMID- 2099230 TI - [The doctrine of homeopathy. A past without a future]. PMID- 2099231 TI - [Medicine and physicians in the works of Georges Simenon]. AB - When reading the novels of Georges Simenon, one is surprised by the high prevalence of doctors in medicine, general practitioners, specialists or university professors. With a few remarkable exceptions, most of these figures appear under a most positive angle: serenity, seriousness, devotion, scientific knowledge, social and professional success. We suggest that the origin of this phenomenon must be searched in the life of the novelist himself. Indeed, the young Simenon has been in contact with a major city hospital, the "Hopital de Baviere" in Liege, where he was serving the early morning mass and was accompanying the priest to the dying, and with students in Medicine renting accommodation at his parents' house. Simenon had looked to study medicine and had to change his plans being told at the age of 15 that his father, suffering angina pectoris, would not survive more than 2-3 years. The prognosis was correct and this greatly impressed Simenon. At the age of 40, the novelist was given for himself the same diagnosis and prognosis, obviously erroneous this time... This event led him to write his first autobiographical work "Pedigree". All his life long, Simenon has had a major interest for Medicine, entertaining a significant personal collection of medical books and journals and having personal contacts with many physicians, some of them illustrious. We believe that all this has had a significant impact on the topics and the characters of his novels. PMID- 2099232 TI - [Evaluation of medical faculties in France]. AB - A "comite national d'evaluation" founded in 1985 scrutinizes the french universities, autonomous but still partly run by the government. So far 17 medical faculties have been examined. Here are presented some remarks on the following points: the selection of the students and the end of the first year and the fate of those who failed; the reinforcement of science teaching for the students eager to go into research or academic medicine; the links binding teaching and research; the international relationships; the impulse of the evaluation on the Faculte. PMID- 2099233 TI - [Europe 1993 and drugs]. PMID- 2099234 TI - [Clinical and surgical anatomy studies of the lymphatic circulation of the pancreas]. AB - Data were collected from results of injection and dissection of 100 autopsy specimens; the examination of 34 case-reports of cancers patients; the injection of lymphatics in 14 live dogs; and the reconstruction of the mesodorsal region of the pancreas from a 30 mm embryo-using Born's technique. Anatomy of the pancreas and lymph vessels shows that the "primary mesodorsal region" of the pancreas is two-fold: a right part for the right side of pancreas, the retroportal process (RPP); a left part for the left side of pancreas, a formation not previously described, the left lateroportal process (LLPP). Whereas lymphatic drainage visible on the anterior surface of the pancreas is apparently as described, posterior drainage, which collects lymph from posterior and anterior vessels, is quite atypical. The right portion drains into the RPP and the left into the LLPP. The very rapid passage into the thoracic duct probably greatly diminishes the value of widely extended surgery. The lymphatic system acts as a "buffer system" or "safety valve", against progression to necrosis. Development and study of a lymphagogue drug for the treatment of acute pancreatitis are a justifiable project. A protocol is proposed which combines lymphagogue treatment with anti enzymes. PMID- 2099235 TI - [Comparative evaluation of the gastric transit of floating and non-floating matrix dosage forms]. AB - The gastric transit of floating and non-floating matrix dosage forms has been studied by means of a gamma scintigraphic imaging technique. Results indicate that, on the one hand, buoyancy and non-buoyancy of the forms lead to distinct intragastric behaviours and that, on the other hand, a selective gastric retention is operated in function of the diametral size of the matrix. Depending on the subject posture, standing or supine, the gastric residence period of the form is hence determined either by its buoyancy or by its size. As sustained drug delivery systems, the floating dosage forms globally offer several advantages which might be worth taking into account. PMID- 2099236 TI - Immunohistochemical and molecular analysis of beta 1 and beta 3 integrins. AB - The expression and function of integrin subunits was examined by immunohistochemical staining of normal and malignant tissues and by producing specific changes in avian beta subunit cDNA that were subsequently expressed in mammalian cells. Most tissues express only a restricted number of integrins. These include primarily those thought to function as collagen/laminin receptors. With the exception of metastatic melanomas, tumors show a general down regulation of integrins. Structure/function studies of the beta subunit show that the cytoplasmic domain is required for inclusion in adhesion plaques and for promotion of adhesive functions; that the transmembrane domain is required for subunit association, but not proper alpha subunit selection; and that the amino terminal one third of the subunit must remain intact for subunit selection and ligand binding to occur. PMID- 2099237 TI - Ligand binding to integrins: common and ligand specific recognition mechanisms. PMID- 2099238 TI - Integrins in human cells and tumors. AB - We have studied the distribution of the alpha- and beta-subunits of integrins in developing and adult human kidney as well as in selected other tissues and cultured cells. In cultured cells some of the integrin subunits (beta 1, alpha 1, alpha 2 and alpha 5) colocalize with talin at focal adhesions when plated on an appropriate ligand. Similarly, in tissues the polarization of beta 1-integrins in colocalization with talin appears to indicate adhesive complexes, as demonstrated in adult glomeruli. In human kidney, the alpha subunits of integrins were seen to be segment-specifically expressed already in fetal tissues. In glomeruli the integrin alpha 1 subunit characterized mesangial cells while the alpha 2 and alpha 3 subunits showed immunoreactivity in endothelial cells and podocytes, respectively. In renal tubuli, the alpha 6 subunit, complexed with the beta 1 subunit, showed a typical polarized distribution coaligning with the tubular basement membrane while the alpha 3 and alpha 2 subunits were expressed in distal tubular cells. These results suggested that in kidney the alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1 integrins can function as basement membrane receptors. The alpha 5 subunit was nearly lacking in the kidney and it appears to be mainly expressed in some smooth muscle cells. In other tissues distinct patterns in the expression of integrins were found. Thus, in many glandular epithelial cells the alpha 3 beta 1 integrin appeared to function as a basement membrane receptor while in various stratified epithelia and in the breast such a polarized localization could be found for the alpha 6 beta 4 integrin. Finally, although presenting a clearly polarized distribution for beta 1 integrins, none of the alpha subunits could be found in cardiac or skeletal muscle cells and none of the integrins could be revealed in neuronal cells of human developing and adult cerebrum or cerebellum, although neurons in peripheral tissues contained abundantly the alpha 6 beta 1 integrin complex. In human tumors, the tumor cells, including also metastastatic tumors, generally presented the same integrins as their tissues of origin. In some poorly differentiated tumors both a population heterogeneity and even a lack of expression or a disorganization of basement membrane receptor integrins was obvious. PMID- 2099239 TI - Role of cell-matrix contacts in cell migration and epithelial-mesenchymal transformation. AB - Epithelial cells make contact with extracellular matrix via receptors on the basal surface that interact with the basal actin cortex. In 3D matrix, the mesenchymal cell makes contact with matrix all around its circumference via similar receptors. When moving, the fibroblasts is constantly constructing a new front end. We postulate in a 'fixed cortex' theory of cell motility that the circumferential actin cortex is firmly attached to matrix and that the myosin rich endoplasm slides past it into the continually forming new front end. During epithelial-mesenchymal transformation, the presumptive mesenchymal cell seems to turn on the new front end mechanism as a way of emigrating from the epithelium into the underlying matrix with which it makes 'fixed' contacts. Master genes may exist that regulate the expression of epithelial genes on the one hand, and mesenchymal genes on the other. PMID- 2099241 TI - [Two surveys on pulmonary embolism]. PMID- 2099240 TI - Transforming growth factor-beta 1 induces extracellular matrix formation in glomerulonephritis. AB - Extracellular matrices can be important in disease. Glomerulonephritis is an inflammation of the kidney that is characterized by the accumulation of extracellular matrix within the damaged glomeruli. We have shown that transforming growth factor-beta 1 (TGF-beta 1) is unique in regulating the production of proteoglycans and matrix glycoproteins by glomerular cells in vitro. In an experimental model of glomerulonephritis in rats, we found increased proteoglycan and fibronectin synthesis by cultured nephritic glomeruli, which was greatly reduced by the addition of antiserum to TGF-beta 1. Conditioned media from glomerular cultures, when added to normal cultured mesangial cells, induced elevated proteoglycan synthesis. The stimulatory activity of the conditioned media was blocked by addition of TGF-beta 1 antiserum. Glomerular histology showed mesangial matrix expansion in a time course that roughly paralleled the elevated proteoglycan synthesis by the nephritic glomeruli. At the same time there was an increased expression of TGF-beta 1 mRNA and TGF-beta 1 protein in the glomeruli. Administration of anti-TGF-beta 1 at the time of induction of glomerulonephritis suppressed the elevated extracellular matrix production and dramatically attenuated histological manifestations of the disease. A small proteoglycan, decorin, also inhibits the activity of TGF-beta, potentially providing an alternative format for the prevention of TGF-beta activity. Our results provide direct evidence for a causal role of TGF-beta 1 in the pathogenesis of the experimental disease and suggest a new approach to the therapy of glomerulonephritis. PMID- 2099242 TI - [Myocardial retroperfusion: the idea, the experimentation, the clinical perspectives]. PMID- 2099243 TI - Catecholamine injections in canine paravertebral ganglia produce hypotension by neurogenic vasodilatation. AB - In the present study the alpha 1 selective agonist phenylephrine (PE), the alpha 2 selective agonist clonidine (CLO) and the non-selective endogenous catecholamine norepinephrine (NE) and dopamine (DA) were injected directly into the blood supply of the paravertebral sympathetic ganglia (PSG) of anesthetized open-chest dogs. Intra-arterial injection of all agonists produced dose-dependent decreases in mean arterial pressure (MAP) and femoral vascular resistance (FVR) but had no effect on heart rate. Their potency order was CLO greater than NE greater than PE greater than DA. Intravenous injections of the medium dose for NE and PE produced significant increases in MAP, while the medium dose of CLO injected iv produced a small decrease in MAP. The ganglionic blocking agent, hexamethonium (10 mg/kg iv) completely eliminated the hypotensive response to all agonists. Intra-arterial administration of the alpha 1 selective antagonist terazosin (0.5 mg) significantly reduced the decrease in MAP produced by the ganglionic actions of PE, but had no significant effect on the response to CLO. In contrast, the alpha 2 selective antagonist rauwolscine (100 micrograms) significantly reduced the decreases in MAP produced by ia CLO, but not that produced by ia PE. However, both antagonists inhibited the hypotensive effect of NE and DA. These findings suggest that both subtypes of alpha-adrenoceptors, alpha 1 and alpha 2, are present in the PSG and that both subtypes are inhibitory since their activation results in reduced transmission of impulses through the ganglia. PMID- 2099244 TI - [Exponential analysis of the relationship between ST segment depression and heart rate during exercise in patients with ischemic cardiopathy]. AB - ST segment displacement sensitivity and specificity during exercise in the detection of myocardial ischemia are controversial, even when using mathematical approaches such as a linear regression analysis of ST/heart rate slope. In an attempt to see whether an exponential fit (ST = A-B*exp (-K*RR] of ST/heart rate relation during exercise could increase the diagnostic accuracy of exercise test in the detection of myocardial ischemia, we studied 165 patients (141 men and 24 women, mean age: 56 +/- 10 years) undergoing a simultaneous radionuclide assessment of regional ventricular function and myocardial perfusion at rest and at peak exercise in 4 hours by means of 2 injections of 99mTc-MIBI. Normal radionuclide findings were found in 4 subjects, whereas exercise-induced myocardial ischemia was detected in 90 patients with no evidence of previous myocardial infarction, and in 71 patients with previous myocardial infarction. ST segment depression was present at peak exercise in no normal subject, and in 52.2% and 60.4% of ischemic and infarcted patients, respectively, achieving a sensitivity of 55.9%, a specificity of 100% and a diagnostic accuracy of 57%. A, B and K coefficients of exponential analysis showed a wide variability among patients; however, the algebraic sign of K coefficient was negative in 50% of normal subjects versus 9.9% of patients (chi 2-test: p less than 0.02), thus achieving a sensitivity of 90.1%, a specificity of 50% and a diagnostic accuracy of 89.1% in the detection of exercise-induced myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099245 TI - [Noninvasive ambulatory monitoring of arterial pressure in hypertensive patients: inside or outside the hospital?]. AB - To investigate whether hospitalization may influence the circadian rhythm of blood pressure (BP), 15 untreated patients with essential hypertension underwent noninvasive ambulatory blood pressure monitoring twice, at home and in the hospital, in a random order, 11 days apart. During the hospital session, which took place on the ninth day of hospitalization, patients were allowed to move freely in the hospital area, to receive visits by friends and relatives and to engage in social activities with other inpatients. Home sessions were performed during a usual working day in 14 of 15 patients. Average 24-hour systolic/diastolic BP was 151/93 mmHg (DS 19/10) at home and 154/93 mmHg (DS 21/7) in the hospital; average daytime (6am-10pm) values were 155/97 mmHg (DS 19/10) at home and 157/96 mmHg (DS 20/5) in the hospital; average night-time (10pm-6am) values were 146/88 mmHg (DS 21/12) at home and 150/89 mmHg (DS 23/10). These values did not show any statistical differences (analysis of variance) due to status (home vs hospital), period or sequence. The hourly BP averages of the hospital recording did not differ significantly from the corresponding averages of the home recording. The correlation between hospital and home 24-hour averages of systolic and diastolic BP was close (r = 0.87 and r = 0.78, respectively; p less than 0.01). The chronobiological analysis (single cosinor) showed a statistically significant circadian rhythm of systolic BP in 10/15 patients at home and in 8/15 patients in the hospital (p = NS), and a statistically significant rhythm of diastolic BP in 9/15 patients at home and in 10/15 patients in the hospital (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099246 TI - [Cardiovascular response to sympathetic stimulation in normal subjects with or without familial hypertension]. AB - The aim of our study was to seek out a possible different reactiveness to cardiovascular stimulation tests among normotensives with and without positive family history of essential hypertension. We have studied about 200 inhabitants of Ustica and 49 medicine students, all normotensives according to the World Health Organization and the Joint National Committee criteria. In an isolated room and in a supine position, blood pressure (BP) and heart rate were measured every 30 s for 15 min with an automatic sphygmomanometer. Averages of last 4 measurements were considered baseline values. Then we have carried out mental stress (MS), handgrip and active orthostatism test (AO) in the inhabitants of Ustica; cold pressor test and AO in students. Patients were divided in 2 groups, genetics and controls, on the basis of a positive family history of essential hypertension. The 2 groups, in every sample, were similar for sex, age, body mass index and alimentary and life habits. RESULTS: a preliminary estimation of Ustica sample showed a different prevalence of positive history between hypertensives and normotensives (63.9% vs 46.61%; p less than 0.05) and no difference between hypertensive and borderline patients (63.9% vs 64.2%); BP and heart rate were slightly higher in controls; there was no statistical difference between genetics and controls. CONCLUSIONS: our results can be explained in various ways: pressor dysregulation in candidates for hypertension may be masked in a large group of normotensives; exaggerated pressor response do not exist in genetics or this pressor dysregulation is impossible to find out with the cardiovascular stimulation tests we have used; other mechanisms are responsible for genetic hypertension. PMID- 2099247 TI - [Surgical therapy for prosthetic heart valve endocarditis: immediate results and follow-up]. AB - Between January 1980 and May 1990 17 patients underwent surgery for prosthetic valve endocarditis at Cardiosurgical Department of Bologna University. Ten patients were female and seven male, the average age was 33 years (range 19 to 67 years). The interval from valve replacement to onset of symptoms of prosthetic valve endocarditis was less than 2 months in 5 patients and longer than 2 months in 12 patients. Sixteen of 17 infected prostheses were mechanical and one biological. All patients were surgically treated and the infected prostheses replaced with new valve prostheses. The hospital mortality rate for early prosthetic valve endocarditis was 60%, for late endocarditis was 16.5%, global hospital mortality was 29.4%. PMID- 2099248 TI - Amiodarone-induced concomitant first and second degree sinoatrial block. AB - The occurrence of concomitant first and second degree sinoatrial block due to chronic amiodarone treatment in 1 patient with moderate mitral valve stenosis is described. Discontinuation of amiodarone resulted in the disappearance of such a sinoatrial conduction disturbance. PMID- 2099249 TI - Mycobacterium shimoidei--Alberta. PMID- 2099250 TI - [Malaria situation in China, 1989. Advisory Committee on Parasitic Diseases, MOPH]. AB - According to the case reporting system, malaria cases in the whole country (Taiwan Province not included) in 1989 accounted for 137,540, the incidence being 12.56/100,000, and lethal cases, 60. All these were close to those (134,156, 12.44/100,000, and 53) in 1988, while an insidious increase was in view. On the basis of county/city reckoning, about 984.5 million people reside in 2,576 counties/cities where malaria incidence was less than 0.1 per 1,000 (including non-endemic areas); 80.2 million people in 174 counties/cities with incidence of 0.1-1.0 per 1,000; 29.9 million people in 76 counties/cities with incidence of 1.1-10 per 1,000; and 500,000 people in 5 counties with an incidence above 10 per 1,000. Though malaria incidence in the whole nation continued to decline to some extent, informations from 3 provinces, i.e. southern Yunnan, Sichuan and middle Anhui showed an increase of 18.26%, 33.02% and 33.91% respectively, as compared with the incidence in 1988. This was due to incomplete implementation of malaria intervention strategies and the decrease in mosquito control areas. The general situation could be summarized as follows: in endemic areas with Anopheles sinensis as vector, the malaria incidence was steadily decreasing, malaria cases were few and scattered with the proportion of exogenous cases increasing; whereas in areas with A. anthropophagus, A. minimus and A. dirus as vectors, the prevalence was unstable and focal outbreaks often occurred. Such places were the main endemic areas of malaria. The endemic areas of falciparum malaria covered 69 counties of 5 provinces/autonomous region, while non-indigenous falciparum cases were reported from 73 counties of 8 provinces/municipality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099251 TI - [Epidemiological survey on patients with advanced filariasis in Shandong Province with bancroftian filariasis basically eliminated]. AB - This paper reports on the incidence of advanced filariasis after basic elimination of bancroftian filariasis since 1983 in Shandong Province. Investigation was carried out in a population of 166,776 between 1984 and 1988 in 252 villages of Teng Xian and other 5 counties/cities, the erstwhile highly endemic areas. A total of 1,038 filariasis patients were found with an average incidence of 0.6%. Among them, 383 were with elephantiasis, 357 with chyluria and 298 with hydrocele. 902 cases (86.9%) who suffered the disease before the elimination of filariasis and 136 cases (13.1%) after it, 125 (91.9%) being chyluria cases. The oldest of the 1,038 cases was 86 years of age and the youngest, 6 years of age. The course of duration as 8-74 years in elephantiasis cases, 82.8% of them (317 cases) had previously lymphangitis and/or lymphadenitis. In the past three years 16.4% (52 cases) suffered from prolonged or intermittent acute lymphangitis and/or lymphadenitis. The results of this survey indicated that, after the basic elimination of filariasis in Shandong Province together with thorough clearance of infection source, elephantiasis and hydrocele persisted while new cases of chyluria continued to develop. Therefore, in such areas more emphasis should be put on the treatment of clinical patients. New patients should be surveyed and old patients be treated actively so as to reach the goal of eradicating filariasis. PMID- 2099252 TI - [Changes in the susceptibility of the recipient Aedes aegypti to Brugia pahangi after passive transfer of haemolymph]. AB - Observations were carried out on the changes in the susceptibility of Aedes aegypti (refm) to Brugia pahangi after receiving haemolymph from both refractory (repRR) and susceptible (refm) Aedes aegypti that were previously inoculated with microfilariae plus TC199 (tissue culture 199) or TC199 respectively. The melanization rates of microfilariae in the recipient mosquitoes were determined by dissecting the mosquitoes on day 3, 4 and 5 after haemolymph transfer. In the recipients receiving haemolymph from the refractory donors inoculated with microfilariae plus TC199, from the refractory donors inoculated with TC199 only and from the susceptible donors inoculated with TC199 only, the melanization rates of microfilariae were estimated to be 31.2%, 31.1% and 21.2% respectively. It is suggested that the intensity of melanization of mosquitoes varies with their susceptibility inherited from their parents. Therefore, the melanization rates of microfilariae in the mosquitoes can be taken as one of the indices of their susceptibility. In addition, most (64.3-73.6%) of the recovered melanized microfilariae were found in the abdomen of the mosquitoes while almost all the developing larvae, in the thorax, possibly due to the choice of preferred sites for development in the latter. PMID- 2099253 TI - [In vitro assay for detecting hemolytic toxicity of antimalarials incorporated with microsomal metabolic system]. AB - The in vitro metabolic system comprised NADP co-factors and liver microsomes isolated from male rats pre-treated with phenobarbital, 60 mg/kg, i.p. for 3d combined with a single i.p. dose of 80 mg/kg of naphtholflavone. The 1% RBC suspension was made up from G6PD-deficient rabbit blood. Primaquine, chloroquine and M 8506 at various dosages were incubated at 37 degrees C with the microsomal metabolic system in vitro respectively. The supernatants were incubated with 1% RBC suspension. The OD635nm values of the supernatants were detected after incubation and centrifugation. The results showed that both primaquine and M 8506 exhibited potent hemolytic toxicity at the dose-range of 1.5-3 x (10(1)-10(3) mumol/L, with certain dose-effect relationship, while chloroquine exhibited no hemolytic toxicity. It is suggested that the in vitro assay incorporated with microsomal metabolic system might be a useful preliminary screening method for testing hemolytic toxicity of various antimalarials. PMID- 2099254 TI - [Experimental infection index of Anopheles sinensis and melanization of periodic Brugia malayi larvae]. AB - This paper deals with the infection index of Anopheles sinensis infected with the blood meals of 9 different microfilarial densities (5-300 mf/10 microliters) of periodic Brugia malayi. The results indicated that the mean number of microfilariae (mf) ingested by mosquitoes increased with the mf-density of the blood meal. The infection rates of vectors were 30, 65, 93 and 100%, when mf densities were 5, 10, 20 and 50 mf/10 microliters respectively. Although the infection rate was 100% when mf-densities were larger than 50 (100, 150, 200, 250, 300) mf/10 microliters, the infection intensities were gradually increased from 17.2 to 51.4 and the host efficiencies were decreased from 0.4135 to 0.2328. The infection intensities and host efficiencies of low mf-densities (5, 10, 20, 50 mf/10 microliters) were 1.22-8.40 and 0.5669-0.6356 respectively. Under the condition of 27.5 +/- 0.5 degrees C, RH 75 +/- 5%, the developmental period from mf to third stage larva was 8 days and numerous infective larvae could be harvested when mf-density was 200 mf/10 microliters. The relationship between mf density and host efficiency, number of melanized larvae and susceptibility of vector, experimental infection indices of Kartman and of Wharton were discussed. PMID- 2099255 TI - [Screening of Schistosoma japonicum adult worm genomic DNA library by specific antibody]. AB - S. japonicum adult worm genomic DNA libraries were screened by enzymeimmunoassay. The antigens produced by recombinant lambda gt 11 plaques were transferred to nitrocellulose filters. Clones encoding given antigens were detected with infected rabbit sera (IRS) which were preabsorbed with lysate of induced lambda gt 11 in Y1090 cells. Eight putative positives were picked up from 97 plates in the primary screening and were rescreened a second time, and, 2 of them consistently gave good positive signals in subsequent screenings. One of the phage clones was purified to homogeneity and mixed with Y1089 cells. The expressed products still showed positive when rescreened by ELISA, indicating that the clone encoding S. japonicum antigen could be recognized by IRS. The immunoscreening method described here was able to efficiently isolate single clones encoding S. japonicum antigens. The method has the advantages of screening libraries efficiently, reliably and specifically, and it might open the way to screen genes encoding S. japonicum antigens inducing protective immunity (Fig. 1). PMID- 2099256 TI - [Studies on the strain differences of Schistosoma japonicum in the mainland of China. II. Susceptibility of mammalian hosts]. AB - Six species of animals were percutaneously exposed to cercariae obtained from pools of naturally infected snails from different isolates of S. japonicum in the mainland of China as shown in Tables 1 and 2. Our results indicated that with the exception of rat, all animals under study were permissive host though their worm recovery rates varied with different isolates. The mean prepatent period in different host species were 35.0 +/- 0.8 to 36.4 +/- 1.0 days for Anhui isolate; 34.5 +/- 1.2 to 36.4 +/- 1.2 days for Hubei isolate; 34.5 +/- 1.3 to 35.8 +/- 0.6 days for Sichuan isolate; 35.1 +/- 1.0 to 37.3 +/- 1.9 days for Guangxi isolate and 36.1 +/- 1.9 to 37.8 +/- 0.8 days for Yunnan isolate. In general, the prepatent period was longer in the C57 BL inbred mice, hamsters and rhesus monkeys infected with Yunnan and Guangxi isolates, than that with Sichuan isolate. This result also indicates that the prepatent period of the strain of S. japonicum defined by Dr. Vogel as a Chinese strain which had been originated from the cercariae in infected Oncomelania hupensis hupensis snails from Jiaxing, Zhejiang (Kashing, Chekiang), China, and established in Tropeninstitut in Hamburg since 1937 by repeated passages in dogs and laboratory-bred O. h. hupensis snails, was 5-8 days longer than that of all the isolates under our study, probably due to some behavioral change. We suggest, therefore, that the Vogel's stock of S. japonicum should be termed as "Chinese Vogel strain". PMID- 2099257 TI - [Identification of L. donovani promastigotes from Phlebotomus by monoclonal antibody]. AB - It has been reported by the authors that monoclonal antibody L12G9 produced from target antigens of L. donovani promastigotes, was very useful for detecting promastigotes from artificially infected sandflies. In the present study, detection of promastigotes from artificially infected sandflies by McAb showed that the positive rate correlated with the infection duration of sandflies. 4 days after feeding on infected Chinese hamsters, the sandflies were lightly infected with L. donovani promastigotes with a positive rate of 15.9%, but 10 days later, the sandflies were heavily infected, the positive rate being 100%. Observation has been made on the relationship between the number of promastigotes and mouse blood dilution. The results showed that satisfactory results could be obtained by using monoclonal antibodies in the detection of L. donovani, the number of promastigotes should be over 1 x 10(7)/ml, and the blood meals in sandflies completely digested. If very few promastigotes were present in naturally infected sandflies before identification by monoclonal antibody, the parasites must be grown in NNN medium. Positive result could then be obtained. PMID- 2099258 TI - [In vitro cultivation of Plasmodium falciparum with umbilical cord erythrocyte]. AB - Plasmodium falciparum was cultivated with umbilical cord erythrocytes or with erythrocytes from human adults for 33 days and 50 days respectively. The erythrocyte infection rate increased eightfold to eighteenfold at intervals of three to four days, the highest erythrocyte infection rate being more than 20%. Furthermore, the infection rate of umbilical cord erythrocytes was higher than that of adult erythrocytes at 48, 72 and 96 hours of cultivation, respectively (P less than 0.01). The results suggested that human umbilical cord blood might be a good source of erythrocytes for in vitro cultivation of malaria parasite. PMID- 2099259 TI - [Analysis of amino acids in hemolymph and acid hydrolysates of midguts of Anopheles dirus infected with Plasmodium cynomolgi]. AB - Quantitative determinations of free amino acids in hemolymph and acid hydrolysates of midguts of female Anopheles dirus infected with Plasmodium cynomolgi bastianellii were carried out and the results were compared with those of noninfected mosquitoes. On day 10 after infected blood meal, the contents of methionine, isoleucine, leucine, ornithine, lysine in the hemolymph of infected mosquitoes markedly decreased as compared with those in the controls. However, the quantitative analysis of the amino acids of the acid hydrolysates of the midguts from infected mosquitoes on day 9 after an infected blood meal showed that the content of their total amino acids was 70% more than that in the controls, with special reference to aspartic acid, glutamic acid, valine, methionine, isoleucine, leucine, phenylalanine, tryptophan. PMID- 2099260 TI - [Study on the exoerythrocytic forms of Plasmodium yoelii yoelii in rats and mice]. AB - SD rats and three strains of mice were infected with Plasmodium yoelii yoelii By265 strain by intravenous inoculation of sporozoites via tail vein. Liver tissues were taken 42 hours after infection and serial sections were made and stained by Colophonium-Giemsa method for microscopic examination. The ratio of the average value of major diameter/minor diameter of exoerythrocytic(EE)schizonts of Plasmodium yoelii yoelii in rats and mice of ICR/JCL, C57BL, KM strains was 35.81 +/- 4.56 microns/29.72 +/- 4.08 microns, 28.08 +/- 4.66 microns/23.66 +/- 4.44 microns, 28.14 +/- 4.16 microns/23.63 +/- 3.77 microns, 23.80 +/- 2.42 microns/21 +/- 0 microns, respectively. The results showed that the development of EE schizonts of Plasmodium yoelii yoelii was not synchronous. The EE schizonts in the rat liver were surrounded by Kupffer cells, monocytes and monocyte-derived macrophages. Since the parasitemia disappeared rapidly in rats, and EE schizonts were not well developed in KM strain, it may be considered that ICR/JCL and C57BL strains are more suitable as vertebrate host in Plasmodium yoelii yoelii-Anopheles stephensi system model (Figs. 1-9). PMID- 2099262 TI - [Ultrastructural changes in the body wall and gut of Clonorchis sinensis in rats after albendazole treatment]. AB - The effect of albendazole on the body wall and gut of Clornorchis sinensis was studied with transmission and scanning electron microscopes after albendazole administration to rats infected with Chonorchis sinensis at a single dose of 150 mg/kg. The results showed that swelling and adhesion of the projections of the tegument and gut microvilli occurred 1h after medication. Necrosis and disruption of the projections and the gut microvilli were seen at the 24th h. By the 72nd h, detachment of the partial projections were seen. The dynamic process of the damages observed on the tegument was identical with that of the gut microvilli (Figs. 1-10). PMID- 2099261 TI - [Scanning electron microscopic observations on larvae and young adults of Angiostrongylus cantonensis]. AB - Scanning electron microscopic observations on the structure of the body surface of various larval stages and young adults of Angiostrongylus cantonensis were made. The mouth opening of the first and second stage larvae closes in "Y" form until well developed young adult stage. There are two rows of 6 sensory papillae each around the mouth. With development of the worm, the papillae of the outer row gradually degenerated and could hardly be seen in adult worms. A pair of amphidial pores was present on the external side of lateral papillae of the inner row, being conspicuous in the fourth-stage larvae. There was one excretory pore on the ventral side of the anterior end. The copulatory bursa of the male worms began to develop in the third stage larvae and became well developed in the 25 day young adults. The processes of the development of copulatory bursa were described. The gonopore could be seen in the female worm as early as in the first stage larvae but the anal pore appeared only in the fourth-stage larvae, both of them did not develop completely until the young adult stage of 11 day old (Figs. 1-18). PMID- 2099263 TI - [An approach to the pathologic basis of ultrasonography in hepatic hydatid disease]. AB - The relationship between sonographic image and histological findings of 149 hepatic hydatid cysts was studied in 98 patients with primary hepatic hydatid disease. Sonographic classification was based on the morphology and structure of the cyst, which is thought to correspond to developmental stages of the hydatid cyst. The types were classified as follow: Type I: simple fluid-filled cyst denoted as the early stage of the disease; Type II: with undulated membrane representing detached endocyst secondary to rupture; Type III: with daughter cysts and a formed echogenic material called matrix; Type IV: solid cyst filled with matrix; Type V: calcified cyst. The latter two types were dead cysts, denoting the end of natural fate of the cyst. The natural progression of the cyst from Type I to Type V was correlated with increasing age of the patients. The rate of stainable protoscolices corresponded to the degree of damage of the germinal membrane, which could reflect the viability of hydatid cyst. The damage of germinal membrane happened earlier and was more severe than that of the protoscolices, being the biologic basis of transforming from type II into type III. Our study also showed that normal, damaged and dead cysts accounted for about 1/3 respectively in the clinical cases of hepatic hydatid disease, providing references for evaluating chemotherapeutic effects on hepatic hydatidosis. PMID- 2099264 TI - [Tumor necrosis serum induce Plasmodium falciparum crisis form]. AB - This paper reports that tumor necrosis serum (TNS) containing tumor necrosis factor (TNF) could inhibit Plasmodium falciparum in vitro. TNS was obtained from rabbits given macrophage-activating agent Mycobacterium tuberculosis (BCG) followed by intravenous administration of bacterial endotoxin (LPS). The results showed that TNS dilutions of 1:3, 1:6 and 1:12 could induce disappearance of Plasmodium falciparum (P less than 0.05) after being cultured 6 hours. TNS decreased red blood cell infective rate of the parasites as compared with the control (P less than 0.05) after 12 hours' cultivation. TNS of 1:3 dilution had further effect at 24 hours (P less than 0.05). Morphological observations showed that the growth of schizonts was retarded and abnormal merozoites were found. PMID- 2099265 TI - [Interactions between filaria worms and insect-vectors]. PMID- 2099266 TI - [Interaction of quartz with human erythrocyte membrane--major protein changes and the effect of aluminium citrate]. AB - The changes of the major proteins of human erythrocyte membrane by quartz were analysed by SDS-polyacrylamide gel electrophoresis. The relative mobility of proteins remained unchanged, whilst the relative abundance of Band 3 and PAS-1 proteins decreased (stained with Coomassie blue and PAS). The adsorption of Band 3 on to quartz were dose- and time-dependent. Aluminium citrate can inhibit the quartz adsorptive activity. The results support that the membrane damage of quartz is related to interacting with Band 3 proteins. PMID- 2099267 TI - [A cohort study on the cancer experience among workers exposed to benzidine derived dyes in Shanghai leather-tanning industry]. AB - 901 male workers who have ever been exposed to the benzidine-derived dyes for more than 1 year in Shanghai leather-tanning industry, were investigated about their occupational history, smoking and drinking histories, case history of cancer, and the causes of death. The results showed that there was an excess morbidity of bladder cancer in this population, and the SIR was 273 (P = 0.05) compared with the general population of Shanghai urban. It may be noted that the excess of the bladder cancer was presented mainly in those workers whose ages of the first exposure were under 19 years old, and the bladder cancer incidence seemed to be associated positively with the cumulative duration of exposure. The survey about the smoking history did not show any obvious relationship between smoking and the development of the bladder cancer. Moreover, it was seen that a trend of excessive in incidence of the nasopharyngeal cancer and the lymphosarcoma existed in this population. PMID- 2099268 TI - [An investigation on X-ray features of phalanges unguinal tuberosity for 2292 cases of normal adults]. AB - The phalanges unguinal tuberosity of normal adults are always in different shapes because of many normal variations in anatomy. According to the difference in shape, the authors divided them into three types: smooth type (62.65%), mushroom type (28.40%) and irregular type (8.49%). It seems that the difference in shape forms are related with the person's age. It is of practical importance to distinguish occupational from non-occupational osteolytic lesions of finger's distal end if one bears in mind these normal physiological variations in anatomy. PMID- 2099269 TI - [A study on the characteristics of the occupational metal-fume fever]. AB - Metal-fume fever is an occupational, acute poisoning disease of workers exposed to metallic oxides fume, especially zinc oxide fume is the most common cause. In order to recommend the diagnostic criteria, the authors of this paper mode hygienic investigations in the workplace, and clinical observations on to workers in the zinc metallurgic factories and copper processing factories. Scientific data for were collected this purpose. PMID- 2099271 TI - [The immune response and its dynamic changes of anti-HBs in 98 juveniles vaccinated with native hepatitis B vaccine]. AB - The immune response and its dynamic changes of anti-HBs in 98 Juveniles vaccinated with three doses of native plasma derived HB vaccine (have been were studied and) followed up for three years. The results showed that the cumulative positive rate and its mean S/N values of anti-HBs at T1 were 70.41% and 19.89 respectively, at T3, T6, T12, T24 all 98% and 65.54, 41.75, 53.95, 23.79 respectively. However out of 98 mentioned recipients 18 subjects become negative for anti-HBs at T36. PMID- 2099270 TI - [On the standardization of new chemical risk evaluation with eye irritation test]. AB - Three new chemicals, N-acyl glutamic acid as a stroma of cosmetics, an eye drops for myopia and 2, 4-dichloro-6-nitrophenylaminate (DCNP) as a new herbicide were evaluated with the eye irritation test. Japanese young rabbits were used, the right eye for test, the left as control. Before and after the test, the eye were stained with 2% sodium fluorescein and examined under slit-lamp microscope to observe the damage degree of cornea, and to record the reaction degree of conjunctiva and iris at the same time. Using the draize method to compare with three kinds of granding (method of bayard and hehir, of EPA and of NRC), the results were essentially the same. The severity of reaction to the eye irritation test is closely related to the kind of testing material and the concentration used and the length of time exposed. The standardization of eye irritation test is also discussed. PMID- 2099272 TI - [Effects of various white noise levels on psychological cognition of school children]. AB - In order to work out a hygienic standard for classroom-noise, 149 school children 8-9 yrs of age were put to psychological cognitive tests under the quiet [42 +/- 1dB(A)] and various white noise levels [50-65dB(A)] classroom conditions in 1986. The main results were as follows: Students under the three white noise levels [greater than or equal to 55dB(A)], all obtained significantly higher means of error scores along with the raising of the noise levels, also lower means of brain work-ability index than under the quiet classroom condition [42 +/- 1dB(A)]. The differences obtained between the three white noise levels [greater than or equal to 55dB(A)] groups and the control group were all statistically significant. PMID- 2099273 TI - [Lung cancer mortality in Qidong (1958-1989) and its trend prediction]. AB - An epidemiologic study of lung cancer mortality in Qidong in the years 1958-1989 was performed based on the data from retrospective survey and registry on cancer. The mortality of the cancer was found to be increasing since 1958. For instance, the rate was 1.04/100,000 in 1958, 9.00/100,000 in 1972, and 21.38/100,000 in 1989. Grey dynamic model was used and the equation established was written in the form Yt = (X1 + 285.078676) exp [0.040 851 (t-1)]-285. 078 676. The rising trend in lung cancer leads to the prediction that this disease will rank second instead of stomach at the end of this century, and may eventually overtake liver cancer as the number one cancer death cause two decades later. As a research strategy lung cancer studies in the rural area should be equally stressed. PMID- 2099274 TI - [An epidemiological survey of Clonorchiasis sinensis of 17 counties/cities of Hubei Province Research Institute for Parasitic Diseases]. AB - An epidemiological survey was made on Clonorchiasis sinensis for the first time in 17 counties/cities of Hubei Province in 1988. The pathogen of clonorchiasis sinensis was found in 14 of the 17 counties/cities. Individual examination of some population was carried out and in 7 counties/cities, all the people were found to be infected. The infection rate was more than 10% in some of the places surveyed. Most of the cases were youngsters. The chief mode of infection was the habit of eating undercooked fish or holding fish in the mouth. These results showed that Clonorchiasis sinensis infection has been widespread in Hubei Province and in some areas the infection was serious attention should therefore be paid to its control without delay. PMID- 2099275 TI - New conversion method of metal surfaces for resin bonding. Conversion effects for pure metals in dental precious metal alloys. AB - Excellent adhesion of adhesives to metals can be realized by simply applying liquid Ga-Sn alloy (Adlloy) on the adherend metal surface. This method is only effective on dental precious metal alloys. Five metals, Au, Pt, Pd, Ag, and Cu, included in dental precious metal alloys were converted by this method to determine the most effective pure metal from bonding strength measurements, water durability at the adhesion interface, and ESCA measurements. All metals converted by Adlloy showed excellent bonding strength and water durability, whereas nonconverted metals showed poor water durability. ESCA measurements showed that metal surfaces converted by Adlloy are covered with a 3-6 nm thick Ga and Sn oxide film and that the diffusibilities of Ga in the metals are in the order Ag greater than Au greater than Pt greater than Cu greater than Pd. From the viewpoint of handling, Ag is the most effective metal. PMID- 2099276 TI - Diagnostic imaging of maxillofacial lesions with CT and MRI. AB - Normal anatomy of the maxillofacial regions is clearly shown by both CT and MRI. The use of dental devices causes deterioration in CT and MRI of the tongue and oral floor. A high-resolution bone window display is highly useful in examining bony structures. Contrast CT is useful in diagnosis of tumorous, inflammatory, and vascular lesions. MRI shows the extensions of tumors more clearly than CT, and MRI enhanced with Gd-DTPA is very useful in determining tumor extensions into bony structures. Both CT and MRI should be used in diagnosis of maxillofacial lesions. PMID- 2099277 TI - Observations on the structural features and characteristics of biological apatite crystals. 1. Observation on the shape and arrangement of the cross sectioned enamel crystals. AB - In a series of studies to investigate the structural features of biological crystals, using transmission electron microscope, the observations have been made on the shape and arrangement of the cross-sectioned crystal obtained from cross sections through the body of adult human enamel rod, in the surface layer, and in the middle and deep layers. The shapes of the cross sectioned crystals in the surface layer of the enamel are generally different from those in the middle and deep layers. In the surface layer of the enamel, the cross sectioned crystals show a considerable variation in shape and size, and have an irregular shape. The crystals are densely packed. Each crystal is adjacent to the neighboring one, and usually, the arrangement of crystals have an appearance rather like a "stone wall". In contrast, the cross sectioned enamel crystals in the middle and deep layer, are somewhat small than those in the surface layer, and have greater gaps between the crystals. In the middle and deep layers of the enamel, it is rare for the shapes of the crystals to be irregular, therefore, they retain their original shape, most of which are long and hexagonal. PMID- 2099278 TI - New approach to analysis of rotational panoramic radiography by computer simulation. AB - Computer simulation is an effective method for mathematical analysis of the image of rotational panoramic radiography. Conventional simulation methods have been used only for analysis of imaging factors and prediction of the characteristics of the obtained image. This paper describes a new computer simulation method that analyzes the imaging factors and produces the simulated image itself. The simulation is carried out by reproducing the actual image formation process in the computer. The head phantom for simulation, which represents the human dentomaxillofacial structures as a numerical value from 0 to 4, was constructed by scanning a real head phantom from neck to head with an X-ray CT scanner at a slice thickness of 1 mm and at 1 mm slice intervals. The diverging X-ray beam was expressed as a set of straight lines and was moved according to various parameters. The simulated image obtained was satisfactory for image analysis of rotational panoramic radiography. PMID- 2099280 TI - Pocket depth reduction by tooth types and sites after initial treatment. AB - Differences in pockets depth reduction rates were compared between different tooth types and sites after initial treatment in 41 adult periodontitis patients whose O'Leary plaque records were maintained at less than 10% during initial treatment. Pocket depths were significantly reduced after initial treatment. Response to treatment was good at 15, 25, 14, 24, 33, 43, 31, 41, 34 and 44; but was poor in 11, 21, 17, 27, 37 and 47. Response to treatment was poor on the mesiopalatal surfaces; midpalatal surfaces of 16 and 26; the distolingual surfaces of 17, 27, 37 and 47; and the mesiopalatal surfaces of 11 and 21; but was good on the distobuccal and midpalatal surfaces of 14 and 24, the mesio- and distal-buccal surfaces of 15 and 25; and the mesiolingual surfaces of 34 and 44. The tooth types and root surfaces that require careful attention during treatment were clarified. PMID- 2099279 TI - Frequency analyses of EMG power spectra of anterior temporal and masseter muscles in children and adults. AB - To study the functional change of masticatory muscles during growth and development, frequency analyses of surface electromyogram (EMG) power spectra were carried out. The subjects were six children (five males and one female), aged 4.5 +/- 0.2 years, having full deciduous dentition (Hellman's dental age IIA) and six adults (four males and two females), aged 27.7 +/- 3.8 years, having full permanent dentition. EMG signals were recorded bilaterally by using bipolar silver-surface electrodes from the anterior temporal and masseter muscles while the subjects were chewing gum and while performing maximum clenching in the intercuspal position. A fast Fourier transform algorithm was used to obtain the power-spectral density function and the power spectra of the EMG signals. Since the total power value from 62.5 to 1000 Hz was 100 percent, the frequencies at 25, 50, 75, and 90 percent of the cumulative power were calculated. The results showed that the frequencies at every percent of the cumulative power were age dependent and that the EMG power spectra patterns in adult muscles were shifted to significantly lower frequencies than those in child muscles. The shift was probably caused by differences in the proportion of fiber type and fiber size between muscles of children and adults. PMID- 2099281 TI - Effects of epinephrine in local dental anesthetics on plasma catecholamine concentration and circulation. AB - To determine the hemodynamic effects of 40 micrograms of epinephrine in local dental anesthetics, circulatory parameters and plasma catecholamine concentrations were measured for 30 minutes after injection of 2% lidocaine with epinephrine (E-L group) or without epinephrine (L-group) in fully conscious healthy young volunteers. The plasma epinephrine concentrations significantly increased in the E-L group (320.9 +/- 47.9 pg/ml) after the injection, but did not change in the L-group. The plasma norepinephrine concentrations did not change in either group after the injection. The differences in each circulatory parameter between both groups (parameters in the E-L group minus those in the L group) at 5 minutes after the injection were +6% in heart rate, +6% in RPP (rate pressure product), +12% in stroke volume index, +22% in cardiac index, -17% in diastoric blood pressure, -22% in total peripheral resistance, -11% in mean arterial pressure, and +/- 0% in systolic blood pressure. The significant increase in cardiac output and significant reduction in total peripheral resistance results in little change in mean arterial pressure. These results suggest that oral submucosal injection of 40 micrograms of epinephrine accelates the cardiac performance, with little change in blood pressure and heart rate. PMID- 2099282 TI - Historical studies on the striae of Hunter-Schreger. AB - When the ground section of a human tooth is observed through a microscope, the oblique section, or the cross section, the enamel rod is dark and the vertical section it is light. These striae have been called the bands of Schreger. In his book published in 1961, Professor Fujita quoted a paper presented by Preiswerk (1894) as follows: "Schreger found the striae in 1800 (Rosenmuller's und Isenflamm's Beitrage fur die Zergliederungskunst, Bd. I, H. 1, Leipzig), but John Hunter from England reported the same findings earlier. For this reason, such striae were called the bands of Hunter-Schreger in Europe and America. In his paper of 1894, Preiswerk reported that Hunter found the striae in 1780; however, in the second edition of his book, The Natural History of the Human Teeth, published in 1778, Hunter showed an illustration that seemed to be the striae and annotated the illustration. The striae may have been reported even in his first edition (1771), but neither edition of the book is available in Japan." Quoting the first edition of Hunter's book, Hoffmann-Axthelm included the illustration of the striae in his book. Through this book, I found that Professor Fujita's conjecture was correct. Moreover, I recently had an opportunity to read the first and the second editions of John Hunter's book. Accordingly, I am reporting this report. PMID- 2099283 TI - Work study on endodontic treatments by means of practice administration. AB - Work analysis by means of dental practice administration is necessary for every clinical dentist. Generally speaking, endodontics sometimes may ignore the study of the operator's difficulties and/or the patient's time burden. Two dentists had treated 72 teeth on 49 patients with single visits in endodontics in one month. Vital and infected canal treatment needed almost the same working time in our clinical system. Difficult cases and work factors affect working time longer and make the standard deviation larger. Difficulties had caused incisor work to consume more time than premolar treatments. In the case of molars, clinical experience helped treatment on maxilla to be quicker than on mandible. Knack factors were to be revealed in this qualitative study. PMID- 2099284 TI - Epidemiological analysis for the influences of plaque and calculus deposition on prevalence of pocket formation. AB - The influence of plaque and calculus deposition on the prevalence of pocket formation was studied using cross-sectional data from 615 Japanese manual workers aged 18-49. A periodontal pocket with a depth of 4 mm or more from gingival margin to bottom of the pocket was coded as presence of pockets. The oral hygiene status at the specified site was classified into four hygiene patterns as no deposition, deposition of plaque only, deposition of calculus only and deposition of both plaque and calculus. The percentages of six specified tooth types with pocket formation were analyzed according to the local hygiene condition. The results indicate that local oral hygiene produces significant differences in the proportion of teeth with pocket formation in the examined tooth types. The frequency of site-specific hygiene condition were no deposition, deposition of plaque only and deposition of both plaque and calculus, except for the lower central incisors. The teeth without plaque and calculus show no pocket formation in most of the examined tooth types in the subjects aged 18-39, while teeth with plaque and/or calculus indicate high prevalence of pocket formation. It is also revealed that the teeth with both plaque and calculus tend to show higher percentages of pocket formation than those with plaque only. These findings suggest that promotion of a plaque free state would reduce risk for pocket formation to negligible level, and that calculus deposition increase the risk for pocket formation around the teeth with plaque. PMID- 2099285 TI - Present condition of adhesive resin materials used in Japan. PMID- 2099286 TI - Discovery and uses of super-elasticity in clinical orthodontics. PMID- 2099288 TI - Purification and characterization of two major outer membrane proteins from Porphyromonas gingivalis. AB - Outer membrane proteins (OMPs) were extracted from whole cells of several Porphyromonas and Prevotella strains and their OMPs profiles were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The SDS PAGE analysis revealed that OMP profiles of Porphyromonas and Prevotella strains show species-specific patterns and P. gingivalis characteristically had two kinds of major outer membrane proteins (MOMPs). A 53 Kd MOMP from P. gingivalis FDC 381 and a 67 Kd MOMP from ATCC 33277 were purified. Sera from periodontitis patients and healthy subjects were analyzed for immunoreactivities against both the purified MOMPs of P. gingivalis by immunoblotting analysis. The sera from 18 patients reacted to the 53 Kd MOMP, 10 to the 67 Kd MOMP, and only three sera reacted to both MOMPs. The sera of healthy subjects also reacted, but weakly, to either the 53 Kd or 67 Kd MOMP. The SDS-PAGE OMP profiles prepared from 13 clinical isolates of P. gingivalis and immunoblotting analysis of human sera against the two kinds of P. gingivalis MOMPs indicate that periodontal diseases resulting from P. gingivalis are initiated and sustained by at least two MOMPs of P. gingivalis. PMID- 2099287 TI - Enzyme immunoassay and monoclonal antibodies for immunological studies of the mutans group of streptococci. AB - Monoclonal antibodies (MAbs) were prepared from myeloma cells and splenocytes of mice immunized with Streptococcus cricetus HS1 or Streptococcus downei MF25 cells. Various makes of immunoplates were coated with whole cells or purified polysaccharide antigens of oral streptococcal strains and tested for reactivity in enzyme immunoassay (EIA) using the Mabs. It was revealed that different immunoplates had different reactivities. It was also shown that the EIA system and MAbs were useful for the immunological study and identification of oral streptococci. PMID- 2099289 TI - Mandibular movement trajectories and masticatory muscle activities in the rabbit in the sleep and wake states. AB - Jaw movements and masticatory muscle activities were recorded in freely moving rabbits. During 5 hours of continuous recording, three states were recognized, namely, sleep, rhythmical jaw movements, and wake without any major jaw movements. The rhythmical jaw movements included chewing, drinking, and grooming and were similar in characteristics to those recorded in immobilized animals. During sleep, two kinds of masseter muscle behaviors with jaw movement features were recorded: one characterized by a short EMG bursts and a pause in jaw movements, considered similar to clenching, and the other characterized by cyclic bursts and lateral jaw excursion, a grinding-like movement. The latter was correlated with light sleep, thus suggesting a resemblance between the grinding like behavior and bruxism. PMID- 2099290 TI - Taste responses to electrolytes in the frog glossopharyngeal nerve: enhancement by Ni2+ ions. AB - In studies of whole-nerve recordings from the frog glossopharyngeal nerve, Kashiwagura et al. reported that Ni2+ enhances responses to MgCl2 and NaCl and that such enhanced responses are suppressed by Ca2+. In the present study, it was found that the responses to electrolytes of single water fibers of the frog glossopharyngeal nerve are enhanced by Ni2+. Ni2+ enhances the responses to MgCl2, NaCl, and CaCl2. The enhancement of the response to CaCl2 suggests that inhibition of the enhanced response by Ca2+ is not caused by the relationship between Ca2+ and Ni2+ ions on the receptor membrane. Kitada reported that, in the absence of Ni2+, Ca2+ competitively inhibits the responses to Na+ and Mg2+; and Kitada and Shimada reported that the response to Ca2+ is competitively inhibited by Na+ and Mg2+. The possibility is discussed that inhibition of the enhanced response by Ca2+ is due to competition between Ca2+ and Na+ and between Ca2+ and Mg2+ for multiple specific receptor sites. PMID- 2099291 TI - Study of the internal structure of the infantile zygomatic bone. AB - External measurements of the zygomatic bone have been reported, but there are no reports on the internal structure. We studied the internal structure of the zygomatic bone and determined the changes in cortical bone width, cortical bone ratio to total cross-sectional area, and trabecular bone width through six periods of tooth growth and development. Zygomatic bone were fixed in resin and sliced, then the cross-sectional specimens were photographed with soft X-rays. The images were analyzed with an image processor. The specimens included the surrounding cortical bone and its internal spongy substance. The cortical bone width, cortical bone ratio, and trabecular bone width increased significantly from the period of deciduous dentition to the first early period of mixed dentition, but leveled off after that. This indicates that in addition to the growth and development of the zygomatic bone itself, its structure is also affected by the forces generated in the maxilla by mastication. PMID- 2099292 TI - Nanospace theory for biomineralization. AB - The precipitation of inorganic crystals from body fluid requires (A) elimination of the macromolecules that inhibit for crystal formation, (B) sufficient supersaturation of the relevant ions, and (C) local restriction of molecular movement. All of these must be accomplished within a space of several nanometers width. Such a nanospace excludes most peptides and oligosaccharides (A). The relaxation time of the outer layer of hydration water (nano second order) on the nanospace wall is 1,000 times longer than that of free water (pico second order). This means that the structure temperature of vicinal water is low, thus the solubilities of calcium ions and phosphate ions are reduced (B,C). Stable ion clusters are formed easier in the nanospace than in the bulk water. The 5-6 nm space in which 3 nm thick hydroxyapatite crystallites can exist should be called critical space. The critical space should be formed according to the fibril diameter and disposition of the fibril or by deployment into the filaments, and by microtubular and lamellar structures. PMID- 2099293 TI - Electronic determination of root canal length by newly developed measuring device. Influences of the diameter of apical foramen, the size of K-file and the root canal irrigants. AB - A new electronic root canal measuring device called "ENDEX" which is able to determine the root canal length under moistened conditions using a relative value of different alternative electric currents is discussed in this study. This study is designed to investigate the efficiencies of the new device, in vitro, with respect to change in the root canal environment; namely the influence of the size of K-file, the diameter of the apical foramen and the various root canal irrigants. According to the present study, it was confirmed that the location of the apical foramen was clearly detected under moistened root canal with saline solution using any size of K-file. The locations of the tip of K-files were 0.5 mm inside the apical foramen when the relative value displayed 0.3 Volt, so that the apical constriction could not disturb during root canal measurement. One of the big problem with prior electrical measurement devices was not being able to determine the canal length under moistened conditions. However with this improved device, intracanal irrigants, such as saline, 5% NaOC1, 14% EDTA and 3% H2O2 did not interfere in detecting apical foramen irregardless of the size of K-file and the size of the apical foramen. PMID- 2099294 TI - Accuracy of complete dental arch impressions and stone casts using a three dimensional measurement system. Effects on accuracy of rubber impression materials and trays. AB - The purpose of this study was to investigate and compare the accuracy of complete dental arch impressions and stone casts made with two kinds of impression materials (addition-type silicone and polysulfide rubber) and trays (custom tray and modified custom tray). In addition, the effect of the quantity of stone was examined. Impressions were made from a metallic model of a simplified maxillary dentition. Impressions and stone casts were measured respectively with a three dimensional measuring microscope. The results were as follows: 1. Distortions of impressions were so small that the reproducibilities of impressions were superior three-dimensionally. These kinds of impressions and trays did not influence the accuracy of impressions. 2. The setting expansion of the stone in the impression occurred in the outward direction and was affected by the kinds of impressions and trays. 3. The arch widths and lengths of the stone casts tended to increase in number. 4. Stone casts made with addition-type silicone impression material and a custom tray were the most accurate because the combination of the impression material and tray effectively suppressed the setting expansion of stone. 5. The accuracy of stone casts could be improved by controlling the quantity of stone. PMID- 2099295 TI - Different resorption modes on living and devitalized bones by isolated osteoclasts in vitro. The effects of TIMP, E-64, and TGF-alpha. AB - A new bone resorption model was developed by using living bone substrates and devitalized bones for isolated osteoclasts to act on. The extent of bone resorption was assessed by measuring the area and depth of resorption pits. The area and depth of pits made on living bones were greater than those of pits made on devitalized bone substrates. TIMP (100 micrograms/ml) reduced resorption on living bone in area and depth to the same amount of resorption on devitalized bone. E-64 (60 microM) significantly inhibited the resorption of devitalized bones. TGF-alpha (100 ng/ml) did not have significant effect on the resorption of any substrate. Indomethacin (100 ng/ml) reduced resorption on living bone to the same level of that on devitalized bone. These results suggest that resorption on living bone is aided by osteocyte-synthesis of metalloproteinases, among them collagenase, to degrade bone collagen through prostaglandin synthesis by viable cells in the substrates. The stimulation of bone resorption by TGF-alpha observed in organ culture appears not to be mediated by direct stimulation of osteoclast activity. PMID- 2099296 TI - Age changes of mandibular condyles and glenoid fossae in mice fed a liquid diet. AB - The effects of the masticatory function on age changes of the temporomandibular joint were studied in 163 C3H/He strain male mice, separated into solid and liquid diet groups from 2 weeks of age. The sizes and shapes of the mandibular condyles and glenoid fossae of the two groups were compared up to 60 weeks. The sizes and shapes of the condyles in the solid diet group increased and developed with age, but there was almost no change after 3 weeks of age in the liquid diet group. The sizes and shapes of the fossae increased and developed with age until 20 weeks in both groups, and there was no differences between the two groups. The poor functional stimulus of mastication has distinct effects on the underdevelopment of the condyle. Since the effects on the fossae were less than those on the condyles, not only the amount of mandibular movement, but also its pattern may have affected the liquid diet group. PMID- 2099297 TI - Clinical study on the prevalence of temporomandibular joint dysfunction in orthodontic patients. AB - The percentage of potential TMJ dysfunction is high in orthodontic patients. The prevalence of TMJ dysfunction during orthodontic treatment and the correlation between TMJ dysfunction occurrence and orthodontic appliances were studied. One hundred and twenty-five male and 183 female orthodontic patients between 7.2 and 38.3 years of age with a mean age of 13.1 years without TMJ dysfunction at first examination were examined for clinical symptoms. TMJ dysfunction was found in 26 patients (8.6%). The frequency of occurrence of TMJ dysfunction in patients treated with a chin cap appliance was 10.9% (14/129) and 6.7% (7/105) for those treated with a multibracket appliance. Chin cap appliance treatment was begun after the pubertal growth peak in eight patients, during the peak in three patients, and before the peak in three patients. Clinical symptoms continued in four patients who continued to use the appliance under the same conditions, and nine patients who were treated with proper countermeasures became free from clinical symptoms. PMID- 2099298 TI - [Comparative anatomical studies of the tongues of Pan troglodytes (Blumenbach, 1799) and other primates. III. Discussion and literature]. PMID- 2099299 TI - Electron microscopic study on the elastic and elastic related fibres in the human fascia transversalis at different ages. AB - An electron microscopic study of the elastic fibre and elastic related fibres of the fascia transversalis of the human inguinal triangle was performed in 20 male patients aged 13 to 81 a with right indirect inguinal hernia submitted to surgical repair. The 3 fibre types comprising the elastic system (oxytalan, elaunin, and elastic fibres) tend to be ordered in a precise manner and sequence among the fibrils, fibres, and collagen fibre bundles, respectively. The present findings show that with aging, there is a decrease in the oxytalan fibres and an increase in the amorphous substance of the elastic fibres. The authors concluded that the decrease in oxytalan fibres as a function of age may be responsible for alteration in the resistance of the transversalis fascia. PMID- 2099300 TI - [The effect of ethyl alcohol on the laryngeal mucosa]. AB - Laryngeal mucous membranes of experimental animals (Rattus rattus L. albino) which were given 25% ethyl alcohol for 4, 10 and 20 weeks was investigated using histochemical methods. It was found that tissues were considerably damaged, especially in the areas covered by stratified squamous epithelium. PMID- 2099301 TI - Characteristic features in the "laryngotrachea" of Suncus murinus. AB - In the larynx of the Suncus murinus (house musk shrew), the cricoid cartilage was situated laterally to and overlapped with the 1st, the 2nd, and a part of the 3rd tracheal cartilages. The term "laryngotrachea" was used for the region maintained by both the cricoid cartilage and the tracheal ones. It is suggested that the condition of the cartilages in Suncus laryngotrachea is the most primitive condition in mammals. In the dorsal wall, just caudal to the plate of the cricoid cartilage and dorsal to the 3rd tracheal cartilage, there existed the "L-shaped cartilage" (named by the authors). PMID- 2099302 TI - Foot morphology development with age. AB - We studied the podogram from both feet in 1676 school-children of both sexes (663 boys and 1013 girls), aged between 3 and 17 a using 3 footprint measures (footprint angle: Clarke [1933]; footprint index of Chippaux [1947] and Smirak [1960]; arch index [Staheli et al. 1987]) and found clear differences according to age. Our findings showed a tendency in both sexes in early childhood to present a low internal arch until the age of 5 and 6a. PMID- 2099303 TI - [The relationship between the gait of humans and the hip joint structure in the frontal plane]. AB - The forces at the hip joint acting between the femur head and acetabulum are significant for the function properties a lifetime. These forces are determined by the geometry of skeleton and the dynamic of limbs motions. The interaction of hip joint anatomy, gait dynamics, and joint force is described biomechanically. The connections are verified by 35 adults. The results of this investigation allow to conclude that individual variants of macroscopic hip joint anatomy are founded by the relation between maximum loading during gait and hip joint structure. The correlation between the angle of weight-bearing-surface and the hip joint force direction is very significant. For a normal hip joint function, the anatomical structure of the acetabulum is essential more important as that of the coxal femur. PMID- 2099304 TI - [The vascularization of the vagina bulbi]. AB - The construction of the vagina bulbi was examined in injection preparations with the aid of microdissection methods, and its layers were defined. Inside the connective tissue leaves occur loop capillaries up to 14 mm in length. The course of the venae vorticosae through the vagina bulbi as well as the width of the episcleral vessel network were measured. Also the subconjunctival network and arteries and nerves perforating sclera were studied. The ascertained results are discussed with former and recent anatomical and clinical reports. PMID- 2099305 TI - [Clinico-anatomical findings of the nasodental nerve]. AB - To avoid neuralgic pain as consequence of damaging the nasodental nerve during surgical treatment of chronic maxillary sinusitis by the Caldwell-Luc-approach, the accurate knowledge of the nasodental nerve's course might be useful for the surgeon. Therefore, the anatomy of this nerve was evaluated by dissection of 23 human specimens. The nasodental nerve is the largest single branch of the infraorbital nerve's Rr. alveolares superiores anteriores. The first course of the nasodental nerve in the roof of the maxillary sinus has a (mean) length of 14 mm on the right and 16 mm on the left side. Mostly it accompanies the infraorbital nerve in the canalis infraorbitalis and leaves this common channel 4 mm on the right and 6 mm on the left behind the infraorbital foramen. The next part of the nerve, which is orientated from laterocranial to mediocaudal, is found in the front wall of the antrum Highmori and has a length of 18 mm at the right and 20 mm at the left. Next it leaves the sinus through a tiny channel at the angle between the front and the medial wall of the maxillary sinus. On the last course, the nerve runs in the lateral wall of the nose 8 mm at the right and 9 mm at the left behind the rim of the apertura piriformis. PMID- 2099306 TI - Formation of extensor digitorum muscle proportions before and after birth. AB - Studies on the formation of the extensor digitorum muscle morphological characteristics were carried out on material of 85 human fetuses (42 males and 43 females), 16 to 36 weeks old, and 45 adults (31 males and 14 females). Intermediary conclusions were drawn on probable changes occurring in the morphological formation of the muscle after birth, as a result of comparing proportions of the muscle at the fetal stage with its form in adults. In this work, the anthropometric method of study and statistical analysis of results have been applied. Analysis of the results in the fetal group has shown that all metrical characteristics of the muscle reach their maximum values at the end of the investigated ontogenetic space. This is, naturally, a consequence of evolution and growth of all fetal body measures, including elongation of forearms. However, the evolution of the individual muscle characteristics is not regular and though the direction of this growth is similar, its extent varies, and also differs slightly in sexual groups. Comparison of the values of muscle indices for 9 month old fetuses with the same indices for adults shows that relative dimensions of all investigated muscular characteristics decrease during the post-natal period except the relative length of the tendon. PMID- 2099307 TI - [Anatomical notes on the capsular veins of the kidney of the cat]. AB - Capsular veins of 36 kidneys in cat (Felis domestica) have been investigated on macroscopical level. There are venous shunts on the superficial renal level which occur in both surfaces (dorsal and ventral) and different pathways of these vessels for comparative diagnosis. The collateral renal circulation may be sufficient to maintain the renal vascularization in stress conditions. PMID- 2099308 TI - [The ligaments and menisci of the femorotibial joint of the wolf (Canis lupus L., 1758)--anatomic and functional analysis in comparison with the domestic dog (Canis lupus f. familiaris)]. AB - Based on dissection of 11 (4 m and 7f) adult wolves (Canis lupus L., 1758) kept in captivity, the morphology and mechanics of the ligaments and menisci of the femorotibial joint are described. Compared with the anatomical data of the dog (Canis lupus f. familiaris), the differences are discussed with respect to their importance for functional considerations. PMID- 2099310 TI - [Cranial morphology of an American siphonopid, Microcaecilia unicolor (Amphibia, Gymnophiona) and its functional interpretation]. AB - The skull of Microcaecilia unicolor, american Siphonopidae (Amphibia, Gymnophiona), shows 3 notable morphological characteristics: The mandibular shortening, the verticalization of the retroarticular process, and the verticalization of the quadrate. They define a peculiar morphofunctional pattern, which seems to exist in dwarf forms moving in the complex root system of trees. These morphological characters, associated with modifications of the muscle depressor mandibulae, give functional advantages: A wider gaping of the mouth and the ability of the ingestion of preys which have a great cross-section. In keeping its macrophageous habits, Microcaecilia unicolor does not compete with other dwarf vertebrates living in the same environment and feeding on microinvertebrates. PMID- 2099309 TI - Effect of lead, zinc, mercury, and copper with and without estrogen on serum vitellogenin level in Magur fish (Clarias batrachus L.). AB - Injection(s) of lead, zinc, and mercuric acetate decreased the serum vitellogenin content in Magur fish, while cupric acetate failed to cause any change in the vitellogenin level. Estrogen injections on 7th, 8th and 9th d increased the serum vitellogenin level in normal and copper salt treated fish, but were totally ineffective in altering the reduced vitellogenin content in lead, zinc, and mercury salts treated fish. Vitellogenin level almost restored to normal level at 6 week in lead, zinc, and mercury treated fish, and estrogen injections on 37th, 38th, and 39th d enhanced the serum vitellogenin content in all groups. PMID- 2099311 TI - On the fine structure of the parotid gland of tufted capuchin monkey, Cebus apella. AB - The parotid gland of the tufted capuchin monkey (Cebus apella) was examined by scanning and transmission electron microscopy. In general the ultrastructural morphology of this gland appears similar to that described in spider and squirrel monkeys. This study has established that the gland is serous. Acinar cells, which contain a well developed granular endoplasmic reticulum and a prominent GOLGI complex, produce a single secretory material. Myoepithelial cells are present around acini and around intercalated ducts. The intercalated ducts, which are composed of cells that show no evidence of secretory activity, lead into striated ducts. PMID- 2099312 TI - [Morphometric studies of the postnatal development of the articular system of the bulbus oculi in rabbits]. AB - The postnatal development of oculo-motor reactions is probably caused partly by changes of the passive mechanical properties of the bulb joint system. The YOUNG's elasticity modulus seems to be a suitable parameter to describe these changes. For its calculation, the length and the cross section area of the extraocular muscles as well as the dimensions of the ocular bulb are necessary. Moreover, the bulb mass is needed to analyse the inertia of the bulb during each movement. The postnatal growth of these parameters was investigated and, by means of the linear regression analysis, we looked for the best fitted mathematical expression. By this, there is the possibility to estimate the morphological data for detailed longitudinal analysis of changes of the oculo-motor function if the age and the body mass, are known. PMID- 2099313 TI - [The morphogenesis of the scapula of Tupaia belangeri]. AB - The therian scapula was until now thought to show very primitive features during early morphogenesis, as are found in the scapula of adult monotremes (elevated position of the scapula, lack of a spina and a fossa supraspinata, laterally directed cavitas glenoidalis). A morphogenetic study of the scapula of Tupaia belangeri has proved some of these assumptions to be wrong. The scapula undergoes a tilting which shifts its angulus articularis cranially, but no descent of the scapula could be found. The supraspinous fossa, which was supposed to develop very late in ontogeny from the anterior border of the scapula (Lewis 1902, Cheng 1955), is present in Tapaiai from the start. Part of it ossifies in membrane. The scapular spine does not develop as a cartilaginous outgrowth from the anterior border, but is formed mainly as an appositional bone along the lateral surface of the scapula. The glenoid cavity and the humerus are initially directed laterally. They attain their definitive form after the heart has migrated downward and the arms have been adducted. This represents a true plesiomorphous character state in therian ontogeny. PMID- 2099314 TI - Cutaneous arterial patterns in the scapular region. AB - The scapular and parascapular cutaneous branches of the circumflex scapular artery were studied in 28 cadaver sides using red latex dissection or lead oxide radiography. 2 vascular patterns have emerged depending on the dominant artery. The 2 patterns have important anatomical implications in reconstructive surgery. PMID- 2099315 TI - [Deterministic chaos--chaotic determinism? A critical review of 2 lectures from the 1989 yearly meeting "Anomalies" of the Leopoldina]. PMID- 2099317 TI - [Endocrine capacity of blastocysts in mammals. I. Progesterone biosynthesis and metabolism]. AB - In order that blastocyst implantation occurs in mammals, it is required the synthesis and secretion of several substances including steroid hormones by the preimplanted embryo. In this paper, we analyze the embryo endocrine capacity for biosynthesis and secretion of progesterone and several progestines. PMID- 2099316 TI - [Uterine contraction. Mechanism, regulation and pharmacology]. AB - Uterine contraction is essential for genital tract functioning among mammal females. For women, the main interest are the possible alterations, and the ability to manage them with drug use. Due to the fact that contraction regulation is multifactorial, several medications are used in basic and clinical research, both to know contraction mechanisms, and to interfere with its alterations. This review considers contraction mechanism at molecular-cellular level, and the different molecules regulating it; as well as the effects that different medications produce upon such mechanism. PMID- 2099318 TI - [Tubal ligation with post-partum minilaparotomy]. AB - This is a review of 209 cases of salpingochlasia by minilaparotomy, post-partum. Frequency was 13.2%. The larger group was 20 to 29 years of age, 52%; 14.3% were unmarried. Multiparae were most frequent, 52.2%. One previous section 3.5%; with four to six live children, 54%. No previous anticonceptive method, 91%; pre-natal control, 69%. With anemia, Hb less than 10 g, 11%, and only 3.5% required blood transfusion. Eutocic delivery, 89%. Ruptured membranes, before delivery, less than six hours, 97%. Anesthesia during delivery, 59.1%; it was epidural anesthesia, as well as for the salpingochlasia in 100%, without complications. The indication was completed parity in 100%, the technique mostly used was Pomeroy's in 77.3%. There were no pre, trans or post-operative complications. The interval between delivery and salpingochlasia in first 12 hours, 98% and from surgery to hospital discharge, 12 to 24 hours, 89.2%. Hospital stay was two days, 90%. Pomeroy's technique failure, 0.6% and for Kroener's, 2.1%. Two pregnancies occurred out of 1,238 months-woman observation. PMID- 2099320 TI - [Terconazole in vaginal candidiasis. A comparative study]. AB - The antimycotic action and tolerance to terconazole in patients with vaginal candidiasis, were evaluated in a blind study. The medication was given in vaginal ovules (VO)240 mg, one dose per day, and 80 mg one daily dose for three days; as compared to chlotrimazole, VO 200 mg, daily dose for three days. The patients presented with vaginal candidiasis demonstrated by Nickerson culture medium. Sixty patients were studied in three equivalent groups. The mates of patients treated with terconazole had no treatment; and the mates of patients treated with chlotrimazole received urinary acidifying medication. Symptomatology and mycologic findings were evaluated at 10 and 28 days post treatment. Mycological cure rates at 10 days were: 90 per cent for the terconazole group, 240 mg, one dose; and 95 per cent for patients with terconazole, 80 mg, daily dose for three days; or chlotrimazole, 200 mg, daily dose for three days. Twenty eight days post treatment, laboratory tests were positive again: 50%, 40% and 15%, respectively. Recidive in patients treated with terconazole, is explained by lack of treatment in mates. In conclusion, terconazole offers a high percentage of clinical and mycological cure in vaginal candidiasis, and it is indispensable treatment for the mate, in order to avoid recidives. PMID- 2099321 TI - Female sex hormones and platelet/endothelial cell interactions. AB - The effects of estradiol and progesterone added to the growth medium of human umbilical vein endothelial cells for 72 h on the formation and release of prostacyclin were investigated. The influence on collagen-induced platelet aggregation and on the platelet formation of thromboxane A2 following aggregation, of the growth medium collected before and after thrombin stimulation of the endothelial cells, was studied simultaneously. Under basal conditions, endothelial cells grown with progesterone released significantly less prostacyclin into the growth medium than did controls (p less than 0.05). Following thrombin stimulation, endothelial cells grown with estradiol (p less than 0.05) or a combination of estradiol and progesterone (p less than 0.01) contained significantly less prostacyclin than controls. No significant effects on the platelet aggregation or platelet thromboxane formation could be found. This study indicates a lowering effect of both female sex hormones on the endothelial cell prostacyclin formation and release. This may be of significance for the increased risk of vascular disease in pregnant women and oral contraceptive users, but can hardly explain the consequences of the hormonal loss occurring at the menopause. PMID- 2099322 TI - Biological and thrombolytic properties of fibrolase--a new fibrinolytic protease from snake venom. AB - Fibrolase, a direct-acting fibrinolytic enzyme has been shown to cleave primarily the A alpha and B beta chains of human fibrin. We have previously reported that fibrolase also exhibits fibrinogenolytic activity and acts mainly as an alpha chain fibrinogenase. In contrast to the action of streptokinase (plasminogen activator), fibrolase does not activate plasminogen. In vitro thrombolytic efficacy of fibrolase was determined by monitoring the release of radiolabel from iodinated fibrin and human blood clots. Fibrolase effectively digested the clots in a dose-dependent manner. The in vivo efficacy of fibrolase was evaluated in an animal model of arterial thrombosis. Fibrolase was found to be efficacious at dissolving femoral arterial clots following a single intravenous bolus administration. Time to reperfusion was dose dependent and similar to that observed with streptokinase. No adverse effects on blood pressure and heart rate were observed. PMID- 2099323 TI - Defibrotide affects the anticoagulant and lipase-releasing activities of heparin. AB - Defibrotide (DEF), an antithrombotic drug with no anticoagulant activity, given concomitantly with heparin potentiates its effects on thrombin time and lipase releasing activity. Unlike heparin, DEF has hardly any lipase-releasing activity of its own. Most likely DEF interferes with pharmacokinetics of heparin. It is clear from the data reported here that when used in combination with DEF heparin should be administered at low doses and the coagulation parameters carefully followed. PMID- 2099324 TI - Evidence for a reduced heparin cofactor II biological activity in diabetes. AB - A reduction of heparin cofactor II (HCII) biological activity, despite its normal plasma concentration, is reported in insulin-dependent diabetic patients. A good linear correlation between HCII activity and concentration is present in normal controls but not in diabetics. In these subjects HCII activity correlates inversely with fasting blood glucose and glycated proteins but not with Hb A1. These data demonstrate the presence of a depressed HCII activity in the presence of its normal plasma concentration in insulin-dependent diabetics and suggest a role for short-term metabolic control in conditioning this phenomenon. PMID- 2099325 TI - Use of adjuvants in modulating the behaviour of Plasmodium berghei. AB - Different adjuvants were assessed for their role in conferring protection against the rodent malarial parasite P. berghei and compared with the classical Freund's complete adjuvant (FCA). Pretreatment of mice with trehalose dimycolate (TDM) mixed with antigen (Ag), sulpholipids (SL) mixed with Ag, muramyl dipeptide (MDP) alone, liposomes containing Ag and phosphomannoinositides (PIM) mixed with Ag were ineffective in conferring protection. However, MDP given with squalane (Sq) and Ag, MDP with incomplete Freund's adjuvant (IFA) and Ag, palmitoyl-MDP with Sq and Ag, aluminium hydroxide adsorbed Ag, and FCA with Ag were effective in conferring varying degrees of protection to mice. Complete protection in rats was obtained with MDP mixed with Sq and Ag, and FCA mixed with Ag, and a partial protection with liposomes containing Ag. PMID- 2099326 TI - Purification and characterization of E. histolytica antigen for diagnosis of amoebiasis. AB - Entamoeba histolytica soluble crude antigen was fractionated by gel filtration on Sephacryl S-300 into four fractions, viz. F1(669 kDa); F2(51.2 kDa); F3(25.1 kDa) and F4(10.5 kDa). F1 fraction was observed to be more sensitive and specific for the detection of antibody in amoebiasis than the crude and other fractions of purified antigens employing IHAT and ELISA. ELISA was found to be better than IHAT since it could detect antibody in the sera (3/6) of asymptomatic cyst passers. The cross reaction of crude antigen with toxocariasis (1/4) and toxoplasmosis (2/5) sera were associated with F4 fraction. F3 and F4 were having low molecular weight and were not sensitive in detection of antibody in amoebiasis. Biochemical characterization revealed glycoprotein nature of the specific (F1) antigen fraction. PMID- 2099327 TI - Excretory/secretory antigens from a bovine filarial parasite cross react with human antifilarial antibodies. AB - Certain excretory/secretory proteins released by adult females of the bovine filarial parasite, Setaria digitata, along with the release of microfilariae when chromatographically analysed has three major protein fractions of molecular weights 70 kD (ESF1), 16.5 kD (ESF2) and 11 kD (ESF3). Of these ESF2 and ESF3 cross reacted with antibodies from Wuchereria bancrofti infected humans. ESF2 was more specific and accurate in detecting human filarial infection. Similar proteins secreted by human filarial parasites could be targets for combating the disease by cure or control. PMID- 2099328 TI - Effect of chromium administration on glutathione cycle of rat intestinal epithelial cells. AB - Acute oral administration of K2Cr2O7 (1500 mg/kg body wt/day) for 3 days to rats led to the decrease in activities of glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase of intestinal epithelial cells. Glutathione and total thiol contents were decreased while lipid peroxidation was increased markedly using the whole homogenate of the intestinal epithelial cells. Chronic oral administration of K2Cr2O7 (300 mg/kg body wt/day) for 30 days to rats on the other hand, led to marked increase in superoxide dismutase and glutathione peroxidase activities with no appreciable change in glucose-6-phosphate dehydrogenase, glutathione reductase and catalase activities. However, glutathione-S-transferase activity was decreased significantly. In the whole homogenate of rat intestine, glutathione and total thiol contents were decreased not so significantly but there was a slight enhancement in lipid peroxidation value. PMID- 2099329 TI - Paw oedema test for detection of Salmonella enterotoxin : modification and standardization. AB - Paw oedema test (POT) was standardized with modifications for the detection of Salmonella enterotoxin. Instead of measuring the weight of the inoculated paws after amputating the limbs at 48 hr post-inoculation, percent relative thickness of the order of 121 +/- 3.8% at 24-48 hr was found to be a better index. This test yielded parallel results to rabbit ligated ileal loop (RLIL) technique. The test was positive with enterotoxic crude cell lysates (CL) and cell free-culture supernatants (CFCS) of S. newport and S. typhimurium, partially purified and purified enterotoxin of S. newport and purified cholera toxin. The test was found to be specific in that non-enterotoxic CFCS did not cause significant increase in the thickness. Minimum detection level of purified S. newport enterotoxin was estimated to be as low as 20 micrograms. Thus, the modified POT was considered to be an effective and economical bioassay model for the detection of Salmonella enterotoxin. PMID- 2099330 TI - Antiparkinsonian activity and dopamine receptor binding studies of imidazolone derivatives. AB - Mannich bases and styryl derivatives of imidazolones were evaluated for their antiparkinsonian activity. Two compounds showed potent antiparkinsonian activity. These active compounds also showed binding with dopamine receptors in striatal membrane preparation of rat brain. PMID- 2099331 TI - Effect of chronic treatment of Ro 15-1788 and its withdrawal on cortical and hippocampal EEG activity in rats. AB - Effect of chronic treatment with Ro 15-1788, a benzodiazepine (BZ) receptor antagonist, and its withdrawal, on the cortical and hippocampal electroencephalogram (EEG) was investigated in rats. Chronic treatment with Ro 15 1788 and its withdrawal (24 and 48 hr) were found to reduce the EEG amplitude in both cortical and hippocampal regions. This reduction in cortical and hippocampal EEG amplitude produced by chronic treatment with Ro 15-1788 and its withdrawal was reversed by gamma aminobutyric acid (GABA), pentobarbitone and picrotoxin, agents known to modulate the GABA/BZ synaptic events by acting at different sites on the complex. Baclofen a GABAB agonist and FG7142, a BZ inverse agonist were found to further reduce the EEG amplitude in the cortical and hippocampal regions of these rats, chronically treated with Ro 15-1788. Diazepam, a BZ agonist was found to have no significant effect on the alteration produced in the cortical and hippocampal EEG amplitude by chronic treatment with Ro 15-1788 or its withdrawal. It is suggested that the conformational changes produced on the GABA/BZ receptor complex by BZ receptor occupation, has a facilitatory effect on the actions of those drugs which act on the GABA/BZ receptor complex and the direction of this enhancement depended on the nature of the drug. PMID- 2099332 TI - Benzodiazepine inverse agonist, DMCM- and peripheral agonist, Ro 5-4864-induced convulsions in mice: effect of adenosinergic agents. AB - Adenosinergic agents such as adenosine, 2-chloro-adenosine, N6 cyclohexyladenosine produced dose-dependent protective effect against DMCM- and Ro 5-4864-induced convulsions and mortality. N6-cyclohexyladenosine produced most significant protective e ect against Ro 5-4864-induced convulsions whereas 2 chloroadenosine was more effective than N6-cyclohexyladenosine in antagonising DMCM-induced convulsions. Pretreatment of animals with subprotective doses of adenosine and dipyridamole significantly prolonged the latencies for the onset of myoclonic jerks and convulsions due to both DMCM and Ro 5-4864. DMCM and Ro 5 4864-induced mortality rate was also significantly reduced by pretreatment with subprotective doses of adenosine and dipyridamole. Similarly, subprotective doses of adenosine and diazepam further delayed the latencies for myoclonic jerks and convulsions due to DMCM and Ro 5-4864 treatment. The results suggest that adenosine and adenosine receptor agonists, 2-chloroadenosine and N6 cyclohexyladenosine are protective against both DMCM- and Ro 5-4864-induced convulsions. It is suggested that adenosinergic agents via activation of central A1 adenosine receptors may modulate the convulsant effects mediated by DMCM and Ro 5-4864. This study further supports the notion that adenosinergic mechanisms mediate neuroprotective e ects in the central nervous system. PMID- 2099333 TI - Comparative evaluation of sequestration of polyamines by perfused rabbit and rat lungs. AB - Differences were observed in the sequestration of polyamines putrescine, spermidine and spermine by isolated, ventilated, perfused rat and rabbit lungs, former being able to accumulate more polyamines compared to the latter. Steady state equilibrium was reached earlier for spermine in rat. Isolated ventilated lungs were perfused with harmaline and ouabain, inhibitors known to inhibit the sodium pump at a maximum concentration of 1 mM for rabbit lungs and 0.4 and 0.2 mM for rat lungs, respectively. They did not affect the uptake of polyamines by rat lung but decreased the uptake of putrescine by rabbit lung. Decreased sodium (50 meq/L) in the perfusate increased the uptake of spermine and spermidine by rabbit lung but again showed no effect with rat lung. However, the uptake of polyamines by isolated ventilated rat and rabbit lungs perfused for 60 min with these compounds was linear over the entire range of high concentrations studied. These results suggest that the major uptake process of polyamines by intact lungs of both animal species is primarily by simple diffusion. HPLC analysis of the perfusate and lungs from both animal species post-perfusion indicated no detectable metabolites of the polyamines. PMID- 2099334 TI - Action of methylglyoxal bis (guanyl hydrazone) and related antiprotozoals on Acanthamoeba culbertsoni. AB - Methylglyoxal bis(guanyl hydrazone) (MGBG) and the related diamidine compounds berenil and pentamidine inhibited multiplication of A. culbertsoni. The growth inhibition by MGBG (2.5 mM) in the peptone medium was accompanied by the disappearance of spermidine and a marked reduction in the level of diaminopropane. MGBG and berenil completely inhibited growth in a chemically defined medium at 1 mM and 1-2 microM concentration, respectively. However, there was no decrease in the polyamine levels in the early stages of growth inhibition by these agents. Uptake of putrescine, spermidine and spermine by A. culbertsoni has been demonstrated but addition of exogenous polyamines did not reverse the growth inhibitory action of MGBG and berenil. Inhibition of S-adenosylmethionine decarboxylase and decrease in polyamine synthesis do not seem to be the primary targets for the antiamoebic action of MGBG and berenil. PMID- 2099335 TI - Effect of aspartate and glutamate on carbon tetrachloride induced liver damage in rats. AB - Liver necrosis was produced in rats by administering 3 doses of a mixture of carbon tetrachloride + olive oil, 2 ml/kg, ip. The liver damage was evidenced by the elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (gamma-GT) and by histopathological observations of liver sections. Aspartate and glutamate administration (100 mg/kg, ip) significantly reduced these elevated levels of AST, ALT, and gamma-GT. Carbon tetrachloride induced liver necrosis was also found to be significantly reduced in aspartate and glutamate pretreated animals as observed macroscopically and histologically. PMID- 2099336 TI - Possible development of dependence on gossypin: role of gossypin on morphine dependence. PMID- 2099337 TI - Simian immune deficiency virus (SIV) strain SIV SMM-PBj 14-4.41 carrying two copies of binding site for transcription factor NF-kappa B induces fulminant disease in pig tailed macaques (Macaca nemestrina) PMID- 2099338 TI - Site of nonrestrictive binding of SEA to class II MHC antigens. AB - We have used the synthetic peptide approach to show that the N-terminal 45-amino acids of staphylococcal enterotoxin A (SEA), SEA(1-45), constitute an important part of its binding site on class II major histocompatibility complex (MHC) molecules. SEA(1-45) and to a lesser extent SEA(1-27) were able to displace SEA from HLA-DR on Raji cells as assessed by flow cytometry and to compete with radiolabeled SEA for interaction with HLA-DR in a direct binding assay. Specific binding of SEA to Ia on murine A-20 cells could be inhibited by the same peptides [i.e. SEA(1-45) greater than SEA(1-27)] that blocked binding to HLA-DR. Therefore, different class II MHC molecules associate with the same functional site on SEA. Further, an ELISA system was used to demonstrate that SEA(1-45) is able to directly bind to a mouse synthetic I-A beta b peptide, I-A beta b (65 85), which contains a binding site of the class II MHC molecule involved in SEA presentation to T cells. Thus, we have localized a site on SEA that is involved in selective surface association with class II MHC antigens and identified the region on the class II MHC antigen to which that site binds. PMID- 2099339 TI - Progesterone triggers selective mast cell secretion of 5-hydroxytryptamine. AB - Mast cells are involved in allergic reactions where they secrete numerous mediators in response to immunoglobulin E and antigen. However, they have recently been implicated in neuroinflammatory conditions with a higher prevalence in women, and there have been clinical reports of progesterone anaphylaxis. When tested on purified rat peritoneal mast cells, progesterone alone stimulated release only of 5-hydroxytryptamine (serotonin) in a dose- and time-dependent manner. Serotonin release by progesterone was exceptional because it was not accompanied by histamine release or degranulation and was either augmented or unaffected by drugs which inhibit secretion induced by the classic mast cell secretagogue, compound 48/80. These findings indicate that mast cells are capable of selective serotonin secretion, previously shown only after pretreatment with certain tricyclic drugs, and may be involved in neuroendocrine syndromes. PMID- 2099340 TI - Anti-cephalexin monoclonal antibodies and their cross-reactivities to cephems and penams. AB - Three cell lines producing monoclonal antibodies (MAbs), Cep1-2, 2-2 and 6, against cephalexin were established and the immunoglobulin class of the MAbs was IgM. The cross-reactions of the MAbs with penams and cephems were examined by enzyme-linked immunosorbent assay (ELISA). The cross-reactivities of Cep1-2 and 2 2 were scarcely influenced by the structures of acyl side chains of cephems and penams. The cross-reactivities of Cep1-2 were affected by the presence or absence of dihydrothiazolidine ring of cephem nucleus in hapten-protein conjugates which were prepared by alkaline method, MBS method and activated ester method but the cross-reactivities of Cep2-2 were not. The findings suggest that Cep1-2 recognize the degradate product(s) of cephem nucleus and Cep2-2 recognize a new antigenic determinant (NAD), which is formed by the conjugation of beta-lactam and carrier protein. On the other hand, the cross-reactivities of Cep6 were influenced by the structure of amino acyl side chain. It seems that Cep6 recognize specifically the acyl side chain at the C-7 of cephem. In ELISA inhibition test, three MAbs showed different inhibition pattern. The reaction of Cep1-2 with cephalexin-HSA was inhibited by cephalexin lysate. Cep2-2 and Cep6 were weakly inhibited by the binding to cephalexin-HSA by cephalexin lysate. Furthermore, the reactions of all MAbs were remarkably inhibited by penicillamine. The above results indicate that the MAbs can recognize at least three epitopes of the degradate product(s) of cephem nucleus, NAD and acyl side chain in cephalexin-protein conjugate. PMID- 2099342 TI - Mast cells, tissue histamine and eosinophils in early- and late-phase skin reactions: effects of a single dose of prednisolone. AB - Skin prick tests with allergen and histamine were performed on the volar aspect of the forearms in a double-blind, cross-over study with 40 mg of prednisolone and placebo in 16 pollen-allergic subjects. Skin biopsies were taken before any treatment and 15 min (group 1; n = 8) and 6 h (group 2; n = 8) after local challenge with allergen, corresponding to the timing of an early- and late-phase reaction. The specimens were used for the histological evaluation of mast cell and eosinophil density as well as for the determination of the histamine and protein content. The size of the induced weal and flare area as well as of any late-phase reaction was determined using digitized planimetry. The single dose of prednisolone, given 2 h prior to challenge, did not affect the size of the weal and flare response. Only 4 of the individuals developed a visible late-phase response. Eosinophils were virtually absent before allergen exposure, but were already present 15 min after allergen challenge, largely associated with the blood vessels, and were numerous at 6 h. There was, however, no relationship between eosinophil density and the presence or extent of any visual late phase. The mast cells/basophils showed a tendency to increase at the 6-hour determination. The infiltration of eosinophils was blocked by the glucocorticoid. This treatment also induced a difference in the mast cell density at the 6-hour determinations, associated with a similar difference in the histamine content of the biopsy specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099341 TI - Effects of ozone exposure on experimental asthma in guinea pigs sensitized with ovalbumin through the airway. AB - As ozone (O3) is known to cause airway inflammation and hyperresponsiveness, we examined the effects of O3 exposure (1, 3, or 5 ppm, 2 h) on sensitization and provocation in guinea pigs sensitized with ovalbumin (OA) through the airway. In groups exposed to O3 before sensitization, 5 ppm increased the production of IgG1 antibodies and decreased the OA sensitization threshold from 0.01 to 0.002%. In those exposed before provocation, 1, 3, or 5 ppm of O3 decreased the OA provocation threshold from 0.5 to 0.02%, and this enhancement appeared to depend on airway hyperresponsiveness. We conclude that O3 exposure may play an important role in causing asthmatic attacks rather than enhancing allergic sensitization. PMID- 2099343 TI - Mast cell activation by hornet (Vespa orientalis) venom. AB - As far as its effect on the activation of rat peritoneal mast cells is concerned, the venom of young hornets (age 0-24 h) differs from that of adult hornets (over 24 h of age). 'Juvenile' venom caused activation mainly in rats previously sensitized to it, whereas 'adult' venom induced activation regardless of presensitization. Furthermore high concentrations of 'adult' venom were cytotoxic to the entire murine peritoneal cell population, but 'juvenile' venom was not toxic. SDS-PAGE data demonstrate that the venom of young hornets contains a unique component (82 kD), nonexistent in adult venom. Our data demonstrate that hornet venom activity is correlated with the hornet's age. PMID- 2099344 TI - Role of immunoglobulins G1 and G2 in anaphylactic shock in the guinea pig. AB - Heating serum from actively sensitised guinea pigs did not remove its ability to sensitise recipient animals in vivo and parenchymal lung strips in vitro to anaphylaxis. Thermoresistant antibodies should thus account for the transferable sensitising effect, which persists for at least 9 days. IgG1 and IgG2, contained in the serum, were separated by affinity chromatography to determine the importance and the participation of these subclasses in passive anaphylactic shock. IgG1, present in smaller amounts than IgG2, was more effective in sensitising isolated lung strips. The intravenous administration of ovalbumin to guinea pigs, which had been injected with 0.8 mg/kg of IgG1 or 2 mg/kg of IgG2 9 days beforehand, induced an intense bronchoconstriction with leucopenia and moderate thrombopenia, suggesting an as yet undescribed role for IgG2 in passive tissue sensitisation. The use of mepyramine, an antagonist of the histamine H1 receptor, WEB 2086, an antagonist of platelet-activating factor, and nordihydroguaiaretic acid, a dual inhibitor of cyclooxygenase and lipooxygenase, alone or associated, demonstrated that the anaphylactic contraction of lung strips from guinea pigs sensitised by IgG1 is mediated by histamine and arachidonate derivatives, whereas that of lung strips from guinea pigs sensitised with IgG2 is mostly mediated by histamine. In addition, the association of the three potential antagonists slightly reduced the anaphylactic contraction of lung strips provided by guinea pigs sensitised by serum. Our results, using a sensitisation procedure considered until now to involve exclusively IgE antibodies, indicate that IgG1 and IgG2 are in fact the essential antibodies for passive anaphylactic shock in the guinea pig. PMID- 2099345 TI - The pathology of the autologous serum skin test response in chronic urticaria resembles IgE-mediated late-phase reactions. AB - The wheal-and-flare response to intradermal autologous serum in chronic urticaria offers a model for study of the pathogenesis of the disorder. Serial biopsies of autologous serum induced wheals were performed in 5 chronic urticaria patients to assess the evolution of the cellular inflammatory response and to look for evidence of mast cell degranulation. Perivascular neutrophils and eosinophils were seen as early as 30 min, becoming more intense and diffuse over 2 h. T lymphocyte numbers were increased by 2 h, CD4+ cells outnumbering CD8+ cells at 24 h. By 48 h, the neutrophils were clearing, but eosinophils and lymphocytes persisted. The histology of compound 48/80-induced wheals was similar to serum induced wheals, but there was little or no response to physiological saline (0.16 M). Stainable mast cells were reduced in compound 48/80- and serum-induced wheals when compared to saline skin tests. Mast cell granules appeared swollen and had lost their characteristic lamellar substructure on electron microscopy of a serum induced wheal biopsied at 10 min. Eosinophil degranulation was also observed at 2 h. The resemblance of the inflammation to the late phase of IgE-mediated immediate hypersensitivity reactions in atopics supports the concept that a circulating factor causes mast cell degranulation in chronic urticaria and may be important in the pathogenesis of the disorder. PMID- 2099346 TI - Increased expression of high-affinity low-density lipoprotein receptors on human T-blasts. AB - Like all cells, lymphocytes need cholesterol for proper function, a requirement met by a finely tuned homeostasis between intracellular synthesis and uptake from the environment via low-density lipoproteins (LDL). We used flow cytometry to analyze the receptor activity of resting cells and T blasts incubated/activated in serum-free culture medium, or in medium supplemented with 25-5,000 micrograms/ml LDL. Dioctadecyl-indocarbocyanine has proved to be a useful fluorescent probe for investigating the LDL receptor activity of lymphocytes. The results show the receptor activity of day-3 resting T cells to be reduced more than 50% by 50 microgram LDL/ml, whereas 100-fold higher concentrations are necessary to achieve the same level of reduction in day-3 PHA blasts. The LDL receptor activities of individual blood donors' resting T cells, in vitro cholesterol-deprived resting T cells, and activated T blasts, were compared using two analytical techniques: spectrofluorometric analysis of detergent-solubilized cell suspensions and flow cytometric analysis of single living cells. Receptor affinity was determined by Scatchard analysis of spectrofluorometric binding curves, and by Line-weaver-Burke plots of flow cytometric data. Both methods yielded essentially identical dissociation constants (Kd) for cholesterol deprived resting T cells and mitogen-activated T blasts, which fell in the expected range for the high-affinity LDL receptor (4.1-8.9 nM). In addition, spectrofluorometric analysis, but not flow cytometry, permitted quantification of LDL uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099347 TI - Ontogeny of mast cells in the ventral prostate of the rat. AB - The ontogenic evolution of mast cells in the rat ventral prostate was studied using the Grimelius silver impregnation method. The mast cell density was highest during the pubertal period and later, it declined significantly with age. Most mast cells were identified in the fibrovascular stroma in close proximity to nerve fibers and blood vessels. The total number of mast cells seems to be constant when correlated with prostatic weight. PMID- 2099348 TI - Lack of correlation between mast cell response and active anaphylaxis in mice. AB - Mast cell-competent mice, sensitized to lysozyme, were examined for their mast cell and anaphylactic responses to determine whether anaphylactic shock could occur independent of mast cell participation. Tissues (cremaster muscle, subdermal connective tissue and mesentery), taken a short time after intravenous antigenic challenge, showed no evidence of mast cell degranulation above control tissues. Data obtained from a quantitative comparison of the onset and increase in local and systemic anaphylactic and mast cell sensitivities to the antigen provide strong support for the view that mast cells are not the major effector cells for systemic anaphylaxis in mice. The significant increase in blood pressure that occurred immediately after infusion with the antigen also indicates that other cells within the blood stream are involved. PMID- 2099349 TI - Immune response to endotoxin isolated from Bacteroides fragilis in the pregnant guinea pig. AB - The humoral immune response to endotoxin isolated from Bacteroides fragilis was analyzed in the pregnant guinea pig by means of passive hemagglutination, passive hemolysis, a modified Coombs test, and by crossed immunoelectrophoresis. Pregnant animals were immunized with endotoxin on day 30 of gestation, and antibodies were determined on day 61 in maternal and fetal sera, and in amniotic fluid. The IgG and IgM responses in maternal sera were of the same magnitude as in sera of nonpregnant animals. Fetal sera contained IgG and sometimes IgM, and a higher percentage of incomplete antibodies against endotoxin than maternal sera. Low titer anti-endotoxin antibodies, partially sensitive to dithiothreitol, were found in amniotic fluid. A statistically significant reduction in the growth of fetuses from endotoxin-immunized females was observed. PMID- 2099350 TI - MTT colorimetric assay detects mitogen responses of spleen but not blood lymphocytes. AB - In an effort to simplify methods for assessing mitogen stimulation of blood lymphocytes, the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) colorimetric assay was compared with the conventional tritiated thymidine deoxyriboside (3H-TdR) incorporation assay. Although able to detect mitogen responses by mouse and rat spleen cells, the MTT assay did not reliably measure blood mononuclear cell responses in mouse, rat or man. The 3H-TdR incorporation assay was effective in every case. Modifications of the MTT assay procedure did not rectify this disparity, which was caused in part by high MTT optical density readings by unstimulated cells. The inability of the MTT assay to detect mitogen responses by blood cells seems to reflect a species-independent physiologic property of these cells. PMID- 2099351 TI - Common German cockroach whole body and fecal allergens: immunoprint inhibition studies. AB - Previous studies have established that cockroach allergens are important sensitizing agents in the induction/exacerbation of urban asthma. The present investigation compared saline extracts of German cockroach (Blattella germanica) whole bodies (GWBE) and feces (GFE) as important sources of allergens. Both extracts were tested prior to or following gel filtration on Sephadex G-75 (Fr2). Immunoprinting of unfractionated fecal extract using 10 RAST-positive sera detected a series of allergens with pI values between 4.15-4.55 and a single allergen that focused near the cathode. Multiple allergens were detected in both GWBE-Fr2 and GFE-Fr2. Generally, most RAST-positive sera reacted similarly, although GWBE-Fr2 had more allergenic proteins than GFE-Fr2 with pI less than 4.7 and fewer allergens with pI greater than 4.7. Immunoprint inhibition of GWBE and GFE by GWBE and GFE also demonstrated allergenic similarity, although homologous extracts were more effective inhibitors than heterologous preparations. Collectively, these studies demonstrate the allergenic similarities of cockroach whole body and fecal extracts. Thus fecal material may provide an important source of sensitizing antigen. PMID- 2099352 TI - Alpha-interferon induces cortisol release by human adrenals in vitro. AB - It is at present not clear whether alpha interferon (INF-alpha) can participate in the control of glucocorticoid blood levels through direct action on the adrenal gland. In this study, the possible action of INF-alpha on cortisol release by adrenal tissue was tested in vitro. Slices of normal human adrenals were incubated with INF-alpha for 3 h at 37 degrees C in 95% air and 5% CO2. Cortisol release by adrenal tissue was stimulated by INF-alpha, showing a dose response curve from 20 IU/ml, the lowest dose that gave a response, to a maximal dose of 60 IU/ml when the response reached a plateau. The effect of INF-alpha on cortisol liberation by adrenal tissue in vitro may be implied in neuroimmune regulatory interactions. PMID- 2099354 TI - Presence of autoantibody against nasal mucosal cells in patients with Wegener's granulomatosis. AB - We examined whether or not patients with Wegener's granulomatosis have autoantibodies against the respiratory tract and kidney, by using the direct avidin-biotin-glucose oxidase complex method. On immunostaining, the IgG fractions obtained from the sera of 2 patients with Wegener's granulomatosis and of 7 controls were coupled with biotin, and each couple was used as the primary antibody. The serum IgG sample from 1 patient with Wegener's granulomatosis definitely reacted with epithelial cells of the nasal mucosa, with the strongest reaction in basal layer. The sample from another patients with Wegener's granulomatosis showed a similar but weaker reaction. Control sera showed negative reactions in 6 subjects (3 with rheumatoid arthritis, 1 with allergic granulomatous angiitis and 2 normal volunteers) and a very weak reaction in 1 patient with poly-arteritis nodosa. These observations suggest the presence of an autoantibody reacting with some cell components of the nasal epithelium in patients with Wegener's granulomatosis. PMID- 2099353 TI - Involvement of type I hypersensitivity in rapid rejection of Trichinella spiralis from adult rats. AB - The role of type I hypersensitivity in the rapid rejection of Trichinella spiralis from actively and passively immunized rats was examined. Net intestinal fluid secretion, which occurs during the rejection of the parasites, was used to verify the expression of local anaphylaxis and was examined for its possible role in the rejection process. Worm establishment in the small intestine 30 min after intraduodenal inoculation was significantly reduced in rats that were passively immunized with immune serum containing anti-Trichinella IgE as compared with recipients of normal serum. Worm-induced fluid secretion in immune rats was completely inhibited by the combined action of indomethacin and diphenhydramine. However, worm rejection was not affected. L-651,392, a 5-lipoxygenase inhibitor, also failed to prevent rejection. Ketanserin (a serotonin S2 receptor antagonist) and MDL-72222 (a serotonin S3 receptor antagonist) together blunted the rapid rejection response and reduced fluid secretion. Furthermore, intra-arterial perfusion of serotonin into nonimmune rats caused fluid secretion and reduced worm establishment. In nonimmune rats prostaglandin E2, cholera toxin, and hypertonic Krebs-mannitol solution were used to evoke the same level of intestinal fluid secretion as that induced by reinfection in immune rats or by serotonin in nonimmune hosts. When larvae were inoculated into the secreting gut, their infectivity was unaffected. The results suggest that anaphylaxis is involved in the rapid rejection of T. spiralis in immune rats and that serotonin is a possible chemical mediator of worm rejection. Although the mode of action of serotonin in the rejection process remains unknown, its possible involvement through fluid secretion can be ruled out. PMID- 2099355 TI - Platelet-activating factor-induced activation and cytoskeletal change in cultured eosinophils. AB - The culture of mononuclear umbilical cord blood cells with low concentrations of interleukin-3 (IL-3) and interleukin-5 (IL-5) for 3 weeks or more results in the consistent production of large numbers of eosinophils. Density distribution analysis and electron microscopic analysis revealed the characteristics of cultured eosinophils to be partially different from peripheral eosinophils. In modified Boyden chamber studies, cultured eosinophils exhibited locomotive activity in response to platelet-activating factor (PAF), with a peak response at 10(-6) M, but not to N-formyl-L-methionyl-L-leucyl-L-phenylalanine. PAF-induced changes in intracellular calcium concentrations in peripheral eosinophils and cultured eosinophils were similar. PAF-induced actin polymerization was observed in cultured eosinophils for the first 30 s followed by depolymerization for the next 10 min. These results suggest that cultured eosinophils respond to PAF in a manner analogous to peripheral eosinophils, and will be useful for in vitro studies. PMID- 2099356 TI - Mast cells in the ovine lower respiratory tract: heterogeneity, morphology and density. AB - The lower respiratory tract (LRT) of 6 adult sheep was fixed in either isotonic formalin-acetic acid or neutral buffered formalin in order to study the heterogeneity, morphology and density of mast cells (MCs). Two subtypes of MCs were found, one histochemically similar to connective tissue MCs (formalin resistant) and the other similar to mucosal MCs as found in the intestine of the rat (formalin sensitive). Although both subtypes were present at all levels of the tract, formalin-sensitive MCs were significantly more abundant (p less than 0.01) at all levels, and their density increased distally from the trachea to the peripheral lung. The formalin-sensitive MCs were predominantly located in the alveolar septa and in the superficial lamina propria of airways and less frequently within the airway epithelium. The MCs in the ovine LRT were found to be morphologically heterogeneous at both the light-microscopic and electron microscopic levels. These findings indicate that ovine respiratory tract MCs have similarity to human lung MCs, and therefore potential for use as a model for the study of human allergic disease of the respiratory system. PMID- 2099357 TI - Pharmacokinetics of diltiazem in patients with liver cirrhosis. AB - The pharmacokinetics of diltiazem (DTZ) was investigated in seven control subjects with normal liver function and in seven patients with liver cirrhosis. After long-term oral administration of diltiazem, 30 or 60 mg thrice daily, serum levels of DTZ and its active metabolites, deacetyl DTZ (DAD) and N-demethyl DTZ (DMD), were determined by high performance liquid chromatography. The mean peak serum concentrations (nmol/L) in control patients were 280 for DTZ, 58 for DAD and 101 for DMD. In cirrhotic patients, the serum DTZ tended to increase and the DAD increased (p less than 0.05), while the DMD decreased (p less than 0.05) compared with that of the control (335 for DTZ, 133 for DAD and 77 for DMD, nmol/L). Pharmacokinetic analysis using a one-compartment model revealed no change in the absorption, but a decrease in the elimination for cirrhotic patients (t 1/2; 5.3 to 7.2 h, p less than 0.1). The elimination rate constant correlated with some biochemical indices for hepatocyte function. These results may be explained by the impaired oxidative metabolism of diltiazem in liver cirrhosis. PMID- 2099358 TI - Blood pressure, plasma renin activity and calcium metabolism in hypertensive pregnancy: the effect of nifedipine. AB - The effects of nifedipine on blood pressure, plasma renin activity and calcium metabolism were studied in nine hypertensive pregnant patients. Nifedipine (10 mg thrice daily per os) reduced blood pressure from 158/103 +/- 4/1 to 150/96 +/- 4/2 mmHg (mean +/- s.e.m.) during 4 to 5 days' treatment (p less than 0.05). The percentage change in diastolic blood pressure correlated negatively with the initial ambulatory (p less than 0.001) and rest (p less than 0.01) plasma renin activity and the initial daily urine calcium excretion (p less than 0.01). Calcium excretion in urine correlated positively with the initial ambulatory and rest plasma renin activity (p less than 0.01). The blood pressure reduction did not correlate with serum ionized, or total calcium, or the initial blood pressure. In six non-pregnant women, the rest plasma renin activity increased (p less than 0.05) after four days' administration of nifedipine. In the patients with hypertensive pregnancy, no changes in plasma renin activity were found during the treatment. The results indicated that the initial plasma renin activity, but neither the serum ionized calcium, nor the initial blood pressure, predicted the blood pressure-lowering effect of nifedipine in hypertensive pregnancy. PMID- 2099359 TI - The effects of timolol on intraocular pressure and exercise heart rate in poor and extensive debrisoquine metabolizers. AB - The effects of a single 20 mg oral dose of timolol, a non-selective beta adrenoceptor antagonist which is subject to hydroxylation in the liver, on intraocular pressure and heart rate were compared in four poor and five extensive debrisoquine metabolizers, using non-contact tonometry and bicycle ergometry. The beta blockade of timolol on exercise heart rate was significantly higher in poor than in extensive metabolisers with no significant difference on resting heart rate or intraocular pressure. PMID- 2099360 TI - Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders. AB - Sixty senile subjects (60-80 years old) with dysthymic disturbances as defined by DSM III (Cat. 390.40) were randomized into two homogeneous groups, one of which was given acetyl-L-carnitine (3 g/day per os) while the other received a placebo. After a washout phase of one week, each patient was evaluated by scoring on the Hamilton Rating Scale for Depression and the Beck Depression Inventory, as well as the Sandoz Clinical Assessment-Geriatric. These tests were administered at the beginning of the trial, prior to drug administration, and repeated during the treatment phase after 30 and 60 days. The results showed that treatment with acetyl-L-carnitine induced a significant reduction, as compared to the placebo (p less than 0.002), in the severity of depressive symptoms and also a significant improvement (p less than 0.0027) in the items measuring the quality of life. PMID- 2099361 TI - Efficacy of cefminox in the treatment of bacterial infections. AB - In an open trial, 1841 patients were treated with mainly 1 g of cefminox twice a day in adults or 20-30 mg/kg three or four times a day in children for up to 14 days. The clinical efficacy was assessed in 1560 patients (1256 adults, 304 children) and the efficacy rates were as follows: 82.3% in respiratory tract infections (n:525), 85.7% in biliary tract infections (n:87), 66.4% in urinary tract infections (n:509), 92.1% in gynaecological infections (n:126), 88.1% in peritonitis (n:84), 74.9% in all infections (n:1560). The overall bacterial response rates in single infections were 81.5% (81.5% for Staphylococcus aureus, 98.4% for Escherichia coli, 98.6% for Haemophilia influenzae and 38.8% for Pseudomonas aeruginosa). The safety of cefminox was assessed in 1831 patients. Adverse side-effects were reported in 35 patients (1.9%), the most frequent being rash. PMID- 2099362 TI - Enzyme-linked immunosorbent assay for detection of molds in cheese and yogurt. AB - An enzyme-linked immunosorbent assay was developed for the detection of molds in dairy products. New Zealand White female rabbits were immunized with .45 mg of partially purified extracellular antigen from freeze-dried culture filtrates of Aspergillus versicolor, Cladosporium herbarum, Geotrichum candidum, Mucor circinelloides, and Penicillium chrysogenum. Blood was drawn at various intervals, and antibodies were separated and purified. Antibody-peroxidase conjugates were prepared with the following ratios being the optimum ones: A. versicolor 10:20; C. herbarum 5:10; G. candidum 1:10; M. circinelloides 5:5; and P. chrysogenum 10:10. The assays were sensitive within a range of 1 ng to 1 microgram/ml, depending on the mold used. Inhibition tests were done for each mold with concentrations of 0 to 5000 micrograms/ml of antigen. The enzyme-linked immunosorbent assay tests for Cladosporium, Geotrichum, and Mucor were only inhibited by antigens from other species of the same genus; whereas there was crossreaction between antibodies and antigens of species of Penicillium and of Aspergillus. Citrate buffer was best for extracting the mold from cheese and yogurt. The extract was adjusted to pH 7.2 and ELISA was performed. Results showed that these molds can be detected in Cheddar and cottage cheeses and yogurt within 2 d, which is before mold growth is visible in these products. PMID- 2099363 TI - Antimutagenic activity of milk fermented by Streptococcus thermophilus and Lactobacillus bulgaricus. AB - Antimutagenic activity of acetone or ethylacetate extracts of skim milk fermented by Streptococcus thermophilus, Lactobacillus bulgaricus, or a combination of both the organisms was studied using Salmonella typhimurium (TA 98 and TA 100). Mutagens used were 4-nitroquinoline-N-oxide (a direct-acting mutagen) and 2 aminofluorene (a mutagen requiring S9 activation). Extracts from all fermented milks showed significant (P less than .05) dose response in suppressing the number of revertants caused by NQNO and 2-aminofluorene in both tester strains, whereas extracts from unfermented milk had no effect. Extracts prepared from milk fermented by L. bulgaricus plus S. thermophilus showed significantly (P less than .05) more antimutagenic activity than extracts prepared from milk fermented by S. thermophilus alone. Solvent (acetone vs. ethyl acetate) effect was not significant with 4-nitroquinoline-N-oxide as mutagen. However, in the case of 2 aminofluorene, acetone extracts showed significantly (P less than .05) higher antimutagenic activity. The results of this and related studies strongly indicate that antimutagenic compounds are produced in milk during fermentation by S. thermophilus and L. bulgaricus. PMID- 2099364 TI - Effect of prolactin infusion on lactation, glucose kinetics, and pancreatic hormones in lactating goats. AB - To determine lactational and glucogenic responses to increased prolactin concentrations, five lactating dairy goats were used in a crossover design. Prolactin at .85 mg/h or placebo was infused on each of 8 consecutive d via jugular catheter for 14 h initiated 30 min after the a.m. milking. To examine the effect of treatments on glucose metabolism, goats were given a single isotope injection of [6-3H]glucose 2 h after initiation of treatment infusion on the final day of the treatment period. Milk yield and milk protein percentage were not affected by prolactin infusion; however, milk fat and SNF percentage were significantly decreased. No differences in dry matter intake and digestibility of the diet were observed. Prolactin increased plasma prolactin and decreased plasma glucagon concentrations, but did not affect plasma insulin or glucose concentrations. Although glucose pool size per kilogram of BW was significantly lower in the prolactin-treated group than in the control group, no difference in glucose turnover rate was observed. PMID- 2099365 TI - Effect of bovine interferon on acute changes in body temperature and serum progesterone concentrations in heifers. AB - Bovine interferon-alpha I1 has extensive sequence and functional homology with the antiluteolytic protein, bovine trophoblast protein-1. Because of the possible use of interferon-alpha I1 as a drug that supplements embryonic secretion of bovine trophoblast protein-1, interferon-alpha I1 was tested for other biological actions that might affect its usefulness as a fertility-enhancing treatment. Experiments were performed to evaluate whether interferon-alpha I1 causes hyperthermia and an acute depression in circulating concentrations of progesterone. In four experiments, intramuscular administration of interferon alpha I1 (range 1.25 to 20 mg) caused hyperthermia; average peak body temperatures of 40 to 40.4 degrees C occurred 2.5 to 6 h after injection. Temperatures returned to baseline 12 to 16 h later. The rise in rectal temperature could be reduced, but not totally alleviated, with concomitant administration of an inhibitor of prostaglandin synthesis. The maximal hyperthermic response was similar when interferon-alpha I1 was delivered via osmotic minipumps or through a series of intramuscular injections. The hyperthermic response decreased with repeated daily exposure to interferon-alpha I1. The increase in rectal temperatures was associated temporally with a decrease in serum progesterone. Effects of interferon-alpha I1 on body temperature and circulating progesterone could possibly limit its effectiveness in enhancing fertility. PMID- 2099366 TI - Determination of milk and mammary tissue concentrations of ceftiofur after intramammary and intramuscular therapy. AB - Twenty-five Staphylococcus aureus strains isolated from bovine mastitis were tested for their susceptibility to ceftiofur. Zone diameter for 30 micrograms disks averaged 39 mm, and minimum inhibitory concentrations ranged from .5 to 1 microgram/ml. Tissue and milk concentrations were determined from biopsy and quarter milk samples collected from eight cows treated with either intramammary infusion of 100 or 200 mg of ceftiofur, one or two intramuscular injections of 500 mg of ceftiofur, or combination therapy of intramammary infusion coupled with intramuscular injection. Three additional cows received two intramammary infusions of 200 mg of cephapirin at 24-h intervals. Intramuscular injections of ceftiofur resulted in tissue and milk concentrations below detectable limits. Staphylococcus aureus was not eliminated from infected mammary glands by infusion of 100 mg of ceftiofur or by injection of 500 mg of ceftiofur by 48 h after treatment. Combination therapy of 100 mg of ceftiofur infused and 500 mg injected reduced S. aureus numbers in milk and tissue markedly, as did infusion of 200 mg of ceftiofur. Cows receiving intramammary infusion of 200 mg of ceftiofur (two doses at 24-h intervals) had highest concentrations in milk (450 micrograms/ml at 4 and 6 h) and in tissue (.08 microgram/mg at 30 h). These concentrations are similar to those obtained with two 200-mg doses of cephapirin at 24-h intervals. Histologic analysis of mammary parenchymal tissues showed that combination therapy resulted in higher percentages of alveolar luminal area and lower percentages of interalveolar stroma compared with infusion or injection alone. Histology of quarters receiving combination therapy was not different from that of quarters receiving cephapirin infusion alone. PMID- 2099367 TI - Protective effect of Staphylococcus chromogenes infection against Staphylococcus aureus infection in the lactating bovine mammary gland. AB - The susceptibility of uninfected or Staphylococcus chromogenes-infected quarters to challenge with Staphylococcus aureus was measured. Seventeen S. chromogenes infected quarters were challenged by infusion of S. aureus into the teat sinus; 47% (8 of 17) became infected and all 18 uninfected quarters challenged similarly with S. aureus became infected. No differences in daily milk yield were seen between uninfected quarters and S. chromogenes-infected quarters prior to S. aureus infusion. Postinfusion, milk yield for S. aureus-infected, S. chromogenes infected, and S. chromogenes- and S. aureus-infected quarters differed. Somatic cell counts were elevated in S. chromogenes-infected quarters compared with uninfected quarters prior to S. aureus infusion. Somatic cell counts were not different between S. aureus- and S. chromogenes- and S. aureus-infected quarters postinfusion, but were different for S. chromogenes-infected quarters. Chloride concentrations in S. chromogenes- and S. aureus-infected quarters were different from either S. aureus-infected or S. chromogenes-infected quarters. Staphylococcus aureus colony forming units in quarters with preexisting S. chromogenes infections were lower than S. aureus colony-forming units in previously uninfected quarters. Possible protective mechanisms induced by S. chromogenes against superinfection by S. aureus are discussed. PMID- 2099369 TI - Plasma osteocalcin in preparturient and postparturient cows: correlation with plasma 1,25-dihydroxyvitamin D, calcium, and inorganic phosphorus. AB - The purpose of the present study was to determine changes of plasma osteocalcin levels in periparturient cows and to examine the correlation of plasma osteocalcin level with that of 1,25-dihydroxyvitamin D, Ca, and inorganic P. Five Holstein-Friesian cows, aged 3 to 5 yr, were used from 5 d before to 15 d after calving. Concentration (mean +/- SE) of plasma osteocalcin decreased rapidly from d 1 prepartum, reached a low of 8.0 +/- 3.0 ng/ml at d 1 postpartum, and then recovered gradually to 17.8 +/- 3.8 ng/ml at 15 d after calving. In contrast, the concentration of plasma 1,25-dihydroxyvitamin D increased from calving to 3 d postpartum. Plasma concentrations of osteocalcin did not correlate significantly with those of 1,25-dihydroxyvitamin D, but it was significantly proportional to that of Ca and inorganic P. It is suggested that osteoblast function is depressed by a number of factors around the time of parturition. PMID- 2099368 TI - Risk factors for clinical mastitis in herds with a low bulk milk somatic cell count. 1. Data and risk factors for all cases. AB - The incidence rate of clinical mastitis in 125 herds with a low annual bulk milk SCC (less than 150,000 cells/ml) was modeled using a Poisson regression model. The rate of clinical mastitis was significantly associated with some variables that increased the exposure to environmental microorganisms: poor cubicle cleanliness increased the mastitis rate; rubber mats in cubicles were associated with a higher incidence; and drinking water from sources other than public water also increased the rate of mastitis. Other variables may be associated with host resistance: an increasing percentage of cows leaking milk increased the rate of mastitis; postmilking teat disinfection was associated with a higher incidence of clinical mastitis; and a high frequency of cubicle disinfection was also associated with more mastitis. Three other variables were associated with the rate of mastitis: breed (Holstein-Friesian had a lower incidence than the Meuse Rhine-Yssel breed); use of sugar beet pulp in the ration increased the mastitis rate; and in herds with high milk production a higher incidence of mastitis was observed. These items are discussed in respect to their causal relation to clinical mastitis. PMID- 2099370 TI - Influence of sodium chloride or potassium chloride on systemic acid-base status, milk yield, and mineral metabolism in lactating dairy cows. AB - Our objective was to evaluate the response of lactating dairy cows to dietary Na, K, and Cl while holding cation-anion balance constant. Fifteen lactating Holstein cows, blocked according to age and previous milk yield, were assigned randomly to replicated 3 x 3 Latin squares with experimental periods of 3 wk. Diets contained sorghum silage and concentrate in a 40:60 ratio (DM basis) and were formulated to provide +32 meq of [(Na + K) - Cl]/100 g diet DM via one of three variations: 1) basal concentrations of dietary Na, K, and Cl, 2) basal diet with addition of 20 meq of Na and 20 meq of Cl/100 g in the form of 1.17% added NaCl, or 3) basal diet with the addition of 20 meq of K and 20 meq of Cl/100 g in the form of 1.56% added KCl. Free proton concentration in blood was increased by addition of NaCl and KCl; however, this increase did not appear to be physiologically significant, and no other measures of acid-base status were significantly affected. Plasma K was higher and plasma Mg was lower for the diets with supplemental NaCl or KCl than for basal diet. Urine mineral excretion reflected dietary mineral concentration, except Ca and Mg excretion rates were reduced by feeding the KCl diet. Milk yield reflected DM intake, which was lowest with supplemental NaCl. Results of this study indicate that, at a dietary cation-anion balance of +32 meq/100 g of diet DM, the balance of Na and K to Cl in the diet is a more important determinant of dietary impact on systemic acid-base status than actual dietary concentrations of Na, K, and Cl. PMID- 2099372 TI - Responses of lactating dairy cows to protected fats or whole cottonseed in low or high forage diets. AB - Thirteen treatments to compare effects of dietary fat on milk yield and composition were control, 15% whole cottonseed, and 2 and 4% Ca-tallowate factorially distributed in low forage (35% corn silage DM) with 14 or 18% CP and high forage (66% corn silage) diets with an additional diet of 8% Ca-tallowate. Different treatments were fed to 36 cows in each of three 28-d periods. Feeding 2 and 4% Ca-tallowate improved milk yield with high forage, although DM intake was slightly depressed; compared with 4% Ca-tallowate, DM intake and milk yield were depressed by 8% Ca-tallowate. Across all diets, whole cottonseed depressed DM intake and milk yield more than when nearly equal fat came from Ca-tallowate (4%). Calcium-tallowate depressed milk fat percentage linearly. Milk fat from cows fed whole cottonseed or Ca-tallowate contained unsaturated fatty acids (mostly C18:1) and lesser quantities of short-chain fatty acids. In a subsequent experiment, Ca-tallowate depressed milk fat percentage, whereas Megalac (calcium salts of fatty acids from palm oil) did not. In a field study, one trial with 210 cows in midlactation showed no effect on milk yield and composition from .54 kg of Megalac/d for 60 d, nor was there any effect detected with 121 cows in early lactation from feeding of .45 kg of Megalac/d for 90 d. PMID- 2099371 TI - Effect of prepartum dietary energy on condition score, postpartum energy, nitrogen partitions, and lactation production responses. AB - Objectives were to examine the effects of feeding to alter body condition at calving on subsequent full lactation production performance and feed intake, on BW and periparturient blood traits, and on complete energy and N balances and ration digestibility during wk 6, 10, and 14 postpartum. Thirty pluriparous Holstein cows were assigned randomly to two energy intakes from wk 33 of previous lactation through the dry period to create either normal (7.2) or thin (5.8) mean body condition scores at calving (9 = fat, 1 = thin). The thin group was fed 0 kg hominy feed daily; the normal group was fed 2.7 kg daily to supplement forage DM available ad libitum during this period. When compared with the normal group, cows in the thin condition group exhibited less negative body fat balance (-206 vs. -507 g/d); similar milk yield, DM intake, N partitions, and nutrient digestibilities; and lower fat test (3.2 vs. 4.1%) during the balance measurements. Whole blood and serum traits were within normal physiological ranges. Full lactation measurements were similar between treatments except that milk fat percentage was lower and DM intake (as percentage of BW), was higher in the thin condition group. Although mean BW at calving was more (651 vs. 599 kg) for normal condition cows, condition scores and BW were not significantly different at 14 wk postpartum; BW curves indicated similar rates of recovery of weight thereafter. Cows considered underconditioned at parturition mobilized less body fat after calving, resulting in reduced milk fat concentration without significant effects on milk yield, protein, SNF, DM intake, or nutrient utilization. PMID- 2099373 TI - Effects of source and amount of protein on ruminal fermentation and passage of nutrients to the small intestine of lactating cows. AB - Four Holstein cows fitted with ruminal and duodenal cannulas were used in a 4 x 4 Latin square to investigate the effects of source (corn gluten meal or soybean meal) and amount (14.5 or 11.0%) of CP on ruminal fermentation, passage of nutrients to the small intestine, and animal performance. Cows wee fed for ad libitum intake a diet of 60% corn silage and 40% concentrate on a DM basis. The treatments, arranged in a 2 x 2 (source x amount of CP) factorial, were 1) 14.5% CP, soybean meal; 2) 11.0% CP, soybean meal; 3) 14.5% CP, corn gluten meal; and 4) 11.0% CP, corn gluten meal. Digestion in the rumen of OM, starch, ADF, and NDF was not affected by source or amount of CP in the diet. Total VFA and NH3 concentrations in ruminal fluid were increased by feeding diets that contained 14.5% CP or soybean meal. FLows of non-NH3 N and amino acids to the duodenum were greater in cows fed the 14.5% CP diets because of a greater flow of non-NH3 nonmicrobial N to the duodenum. Larger amounts of lysine passed to the duodenum when cows were fed soybean meal compared with corn gluten meal. Microbial N flow to the duodenum and efficiency of microbial growth were not affected by treatments, suggesting that ruminal NH3 concentration was not limiting for maximal microbial protein synthesis. Feeding 14.5% CP diets increased the production of milk (29.5 vs. 26.8 kg/d) and milk protein compared with 11.0% CP diets, possibly because of greater passage of amino acids to the small intestine. Feeding soybean meal to cows increased production of milk protein compared with feeding corn gluten meal, possibly because more lysine passed to the small intestine. PMID- 2099374 TI - Effects of feed processing and frequency of feeding on ruminal fermentation, milk production, and milk composition. AB - Twenty Holstein cows, averaging 108 d postpartum, were used in five replicated 4 x 4 Latin squares to investigate the effects of feed processing and frequency of feeding on ruminal fermentation, milk production, and milk composition. Four rumen-fistulated cows were used in one of the replicates to monitor ruminal fermentation. Each cow was fed for ad libitum intake a diet of 55% alfalfa and 45% concentrate on a DM basis. Treatments were 1) noncubed diet fed two times daily, 2) noncubed diet fed four times daily, 3) cubed diet fed two times daily, and 4) cubed diet fed four times daily. Alfalfa was fed as long hay in the noncubed diet and chopped and pressed into a cube in the cubed diet. Dry matter intake by cows was not different between treatment comparisons. However, cows fed the noncubed diet consumed 5% more concentrate and 5% less alfalfa than did cows fed the cubed diet. Milk production was greater (1.4 kg/d) when the cubed diet was fed to cows, but the percentage and yield of milk fat were depressed (.43 percentage units and .09 kg/d), causing a decreased production of 4% FCM (.9 kg/d). The depression in milk fat percentage and yield may have been attributed to lowered ruminal fluid pH and a decreased ratio of acetate to propionate in cows consuming the cubed diet. Even though ruminal fluid pH and the ratio of ratio of acetate to propionate tended to be lower when cows were fed four times rather than two times per day, production and composition of milk were not affected by frequency of feeding the diets. PMID- 2099375 TI - Effects of feeding alkaline hydrogen peroxide-treated wheat straw-based diets on digestion and production by dairy cows. AB - Twelve Holstein cows, averaging 34 d postpartum, were used in three replications of a 4 x 4 Latin square design to determine the effects of feeding different levels of alkaline hydrogen peroxide-treated wheat straw on digestion and production responses in lactating dairy cows. Complete mixed diets consisted of 50% concentrate (DM basis) plus varying proportions of treated wheat straw, alfalfa haylage, and corn silage as the forage source. Treatment contained 0 (control), 12.5 (low), 25.0 (medium), or 37.5% (high) treated wheat straw in the diet. Dry matter intakes were 18.5, 17.2, 17.4, and 16.7 kg/d for the four treatments, respectively. Apparent digestibilities of DM and OM were decreased (approximately 4.4 percentage units), and NDF and ADF digestibilities were increased by 9.4 and 3.0 percentage units, respectively, with the high wheat straw diet. Yields of milk and 4% FCM, and SNF percentage did not differ among the treatment groups. Milk fat percentage increased (from 3.07 to 3.32%) and milk protein percentage decreased (from 2.61 to 2.56%) as the proportion of treated wheat straw increased in the diet. Cows fed the higher proportions of treated wheat straw had increased ruminal concentrations of total VFA and molar percentage acetate but a decreased molar percentage propionate, resulting in a greater acetate to propionate ratio. Cows fed the low and medium wheat straw diets had slightly lower DM intakes but production responses were similar to cows fed the control diet containing alfalfa haylage and corn silage as fiber sources. PMID- 2099376 TI - The use of rapeseed screenings in diets for lactating cows and subsequent effects on milk yield and composition. AB - This trial was to determine the effect of dietary rapeseed screenings on milk production, milk composition, and feed intake of lactating dairy cows. Pelleted rapeseed screenings were fed at 0, 7, and 14% of diet DM. Assignment of 36 multiparous Holstein cows was based upon parity and previous lactation performance. The experimental period was from parturition through wk 16 of lactation. The control ration had 3.1% ether extract, whereas the ration with 14% rapeseed screenings had 5.4% ether extract. The rapeseed screenings contained 52.2% of C18:1 and 24.2% of C18:2 as percentage of total fatty acids. There were no significant effects of dietary treatment on milk yield or feed intake. There were significant increases in milk fatty acids C18:1 and C18:2 for cows consuming the diets with rapeseed screenings. Treatment did not significantly affect milk protein percentage as measured by Kjeldahl N or by the infrared method. Increased unsaturated fatty acids in the milk of cows fed rapeseed screenings had no apparent effect on infrared fat analysis. There was no interaction of treatment and milk fat analysis method (infrared versus Babcock). Dietary treatment did not affect blood serum nonesterified fatty acid concentrations over the 16-wk period. In conclusion, rapeseed screenings, fed at levels up to 14% of the diet, did not affect milk yield, milk protein, or milk fat percentage but did change milk fatty acid composition. PMID- 2099377 TI - Feeding acidified or sweet milk replacer to dairy calves. AB - The objective of this study was to compare performance of calves fed acidified milk replacer or regular (sweet) milk replacer twice daily at 10% of BW. Thirty seven female Holstein calves were fed replacers reconstituted to 12.5% DM for 4 wk, At 28 d, half of the amounts of milk replacer consumed during wk 4 were fed during wk 5 and calves weaned from replacer at d 35 age. A pelleted starter feed was offered for ad libitum access throughout the 42-d trial. Body weight was recorded at birth, d 3 of age, and weekly thereafter. Fecal consistency scores were recorded. Other parameters were measured on d 3 and 42. Average daily gains (d 3 to 42) for calves fed sweet and acidified milk replacers were .33 and .38 kg/d. Starter consumption was similar for both treatments. Calves fed acidified milk replacer (d 3 to 28) had a lower (1.4 vs. 1.6) fecal consistency score than those fed sweet milk replacer (scale of 1 to 4, 1 = normal and 4 = watery). Benefits of feeding acidified milk replacer at 10% of BW per day may be in reducing the incidence of some infectious scours, although further experiments are needed to verify this. PMID- 2099378 TI - Relationships of calving ease with type traits. AB - Type information collected by the Holstein Association of Canada was combined with calving ease data from the Quebec Dairy Herd Analysis Service. Type traits considered were overall score, general appearance, dairy character, capacity, rump, rump thurl width, rump pin setting, and set of rear legs. Calving ease was considered as a direct effect and as a maternal effect in both heifers and adult cows. After editing there were 24,618 type records, 47,023 direct effect calving ease records, and 37,068 maternal effect calving ease records from 107 sires in the analyses of heifer data. there were 26,996 type records, 16,4726 direct effect calvin ease records, and 45,261 maternal effect calving ease records in the analyses of calving involving adult cows. Multiple-trait REML was used to estimate genetic correlations between calving ease and type. The heritability of calving ease in heifers was approximately 4%, for both the direct and maternal effect, and in adult cows was approximately 1.5%. Heritability of the type traits ranged from 4 to 45%. There was a tendency for the genetic correlations between type and the direct effect of calving ease to be opposite in sign to the genetic correlations between type and the maternal effect of calving ease and for the absolute value of the correlations to be lower in adult cows than in heifers. PMID- 2099379 TI - Opioid action on luteinizing hormone secretion in newborn pigs: paradoxical effect of naloxone. AB - German Landrace piglets, 6-7 days of age, received either saline (9 males, 8 females), 0.5 mg naloxone/kg body weight (7 males, 7 females), 2.0 mg naloxone/kg (7 males, 8 females) or 0.5 mg DADLE (potent leu-enkephalin analog)/kg (7 males, 7 females) through a catheter inserted into the jugular vein 2-4 days previously. Male or female piglets were allocated randomly, within litter, to the different experimental groups. Blood samples were withdrawn for a period of 240 min at 10 min intervals for the first 60 min following injection and at 20-min intervals for the rest of the test period. Piglets were separated from their mother via a detachable wall and were allowed to suckle every 50 min. DADLE failed to alter plasma levels of LH in both males and females. Naloxone induced a significant (P less than 0.01) decrease in LH concentrations in females 10 to 60 min after injection (saline: 2.3 +/- 0.2 ng/ml plasma (SEM); 0.5 mg naloxone/kg: 1.0 +/- 0.2 ng/ml plasma and 2 mg naloxone/kg 1.2 +/- 0.4 ng/ml plasma). In males low doses of naloxone reduced plasma LH levels 10 to 40 min after injection (saline: 2.0 +/- 0.3 ng/ml plasma and 0.5 ng naloxone/kg: 1.1 +/- 0.3 ng/ml), whereas a decrease in plasma LH levels occurred 80 to 140 min after injection of high doses of naloxone (saline: 2.1 +/- 0.2 ng/ml and 2 mg naloxone/kg: 1.0 +/- 0.2 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099380 TI - Apneic effects of cholecystokinin in unanaesthetized fetal sheep. AB - The effects on breathing movements and sleep state of cholecystokinin octapeptide (CCK-8) and its antagonist, proglumide, have been studied in unanaesthetised fetal lambs of 124-142 days gestation. CCK-8 when given into a lateral cerebral ventricle as bolus injections of 10-500 ng caused dose-related periods of apnea ranging from 63-214 min. When given as a 100 ng bolus followed by a 50 ng/h infusion for 2 h there was a prolonged period of apnea lasting 331 +/- 56 min. There was no effect of CCK-8 when given in higher doses (1-50 micrograms). The antagonist proglumide reversed the apnea induced by CCK-8 infusion, but had no effect when given alone, nor did it affect the normal fetal depressive response to hypoxia. Neither CCK-8 nor proglumide had any effect on electrocortical activity. We conclude that CCK has no role in the inhibitory mechanisms causing the apnea associated with high voltage electrocortical activity or hypoxia in the fetus. Furthermore CCK does not appear to be involved in the regulation of sleep state in the fetal lamb. PMID- 2099381 TI - Allelic interactions at the shibire locus of Drosophila: effects on behavior. AB - This report describes a detailed behavioral study of four shi alleles, shits1, shits2, shits4, and shiST139, and their heteroallelic combinations. Flies of different heteroallelic combinations (shi/shi) were less sensitive to high temperature than the corresponding homozygotes. Among them, shits2/shits4 showed a striking reduction in temperature sensitivity. In contrast, different shi/+ heterozygotes were more severe in temperature sensitivity than the hemizygotes, Df/+. The hemizygous combinations of shi alleles over deficiency (shi/Df) were not completely lethal, with shits2 conferring distinctively higher and shits4 lower viability. A novel behavior, bang sensitivity, was also found in shi/Df. The results of allelic interactions suggest that the shi mutations examined appear to be antimorphic and that the shi gene products are likely to function in multimeric form. PMID- 2099382 TI - Mechanisms of intrinsic macrophage--virus interactions in vitro. PMID- 2099383 TI - Dependence on cell-mediated mechanisms for the appearance of crisis forms during Plasmodium chabaudi AS infection in C57BL/6 mice. AB - The appearance of crisis forms or degenerate, intraerythrocytic parasites in the peripheral blood of C57BL/6 hosts during the course of Plasmodium chabaudi AS infection was analysed. Following intraperitoneal injection with 10(6) parasitized erythrocytes, C57BL/6 hosts, which are resistant to this species of rodent Plasmodium, eliminate the parasite from the peripheral blood by 4 weeks and recover from acute infection. Elimination of the parasite coincides with the appearance in the peripheral blood of almost all the parasites as crisis forms. A role for cell-mediated immunity in the induction of crisis forms of Plasmodium species has previously been suggested. To define the role of cell-mediated immunity in the appearance of intraerythrocytic crisis forms in the peripheral blood during acute malaria, the outcome of P. chabaudi AS infection, the course of parasitemia and the appearance of crisis forms in mice with either genetically determined or experimentally induced immunodeficiencies on the resistant C57BL derived background were examined. The mice used were either B-cell deficient (mu suppressed from birth). T-cell deficient (nu/nu mice), C5 deficient or splenectomized prior to infection. The appearance of intraerythrocytic crisis forms in the peripheral blood during the course of P. chabaudi AS infection is shown to be dependent on cell-mediated mechanisms which require the presence of T cells as well as an intact spleen for the most efficient elimination of this parasite. PMID- 2099384 TI - Biological and immunological characterization of a cloned cholera toxin-like enterotoxin from Salmonella typhimurium. AB - A chromosomal DNA fragment, encoding an enterotoxin gene of Salmonella typhimurium Q1, was cloned into bacteriophage EMBL3 and plasmid vector pBR322. The recombinant clones lambda B8 and pC1 were identified using a synthetic oligonucleotide probe made to the B subunit region of the cholera toxin gene (ctx). Cell lysates of Escherichia coli VCS257 [lambda B8] induced fluid secretion in rabbit intestinal loops, while lysates of E. coli DH5 alpha [pC1] failed to elicit an enterotoxic response in this model. Both lysates and partially purified preparations elongated Chinese hamster ovary (CHO) cells, elevated cellular cAMP and PGE2, and bound to ganglioside GM1. The biological activity associated with the cloned enterotoxin was neutralized by monospecific antiserum to cholera toxin (CT). Immunoblots of pC1 and lambda B8 lysates probed with anti-CT, exhibited a 30 kDa protein similar to that of pJM17, which carried the ctx gene. Under non-dissociating conditions, anti-CT immunoblots of the same lysates revealed two proteins, one corresponding in size to the holotoxin and the other to CT-A. When analysed by DNA-directed protein synthesis in vitro, both pC1 and lambda B8 DNA expressed two unique proteins (30 and 11 kDa) similar to that of pJM17. PMID- 2099385 TI - A 28 kDa protein of normal mouse serum binds lipopolysaccharides of gram-negative and lipoteichoic acids of gram-positive bacteria. AB - A 28 kDa protein from normal mouse serum known to bind to the inner core region of bacterial lipopolysaccharide (LPS) was found to bind also to bacterial poly(glycerophosphate) lipoteichoic acid (LTA). Twenty-nine preparations of LTA were isolated from 19 different bacterial species, purified, chemically analysed, and tested for their ability to bind the 28 kDa protein in a complement-dependent hemolysis and hemolysis inhibition assay. All but one were active in one or both systems and one half of the preparations were active in both. Reactivity patterns were not strictly correlated with the chemical structure of LTA considering the substitution of the poly(glycerophosphate) chain with alanine ester and glycosyl residues and the type of lipid anchor. The isolated lipid anchor alone was unable to bind the serum factor. Comparing the binding to LTA and LPS from Acinetobacter calcoaceticus indicated complete cross-reactivity of LTA and LPS in various serological approaches. Thus, LPS and LTA which are unique amphiphiles in Gram negative and Gram-positive bacteria, respectively, share a similar function in terms of binding the 28 kDa mouse serum protein. PMID- 2099387 TI - The effects of O-(beta-hydroxy-ethyl)-rutosides (HR) on acute lymphoedema in rats' thighs, with and without macrophages. AB - The effect of O-(beta-hydroxy-ethyl)-rutosides (HR), injected subcutaneously, was investigated on experimental acute lymphoedema in rat thighs. The oedema was reduced from a 30% increase over the normal weight, to one of 13%. When the macrophages were destroyed by the intraperitoneal injection of silica (for eight days before the initiation of lymphoedema) the oedema of the thigh increased to 41% - thus showing the importance of these cells in limiting high-protein oedemas. When HR was given to animals treated with silica the oedema was no longer reduced (42%). Thus HR reduces a high-protein oedema substantially via the macrophages. PMID- 2099386 TI - Constriction of perfused lymphatics by acetylcholine, bradykinin and histamine. AB - We have previously reported that perfused lymphatic vessels in the canine forelimb constrict in response to increased sympathetic nerve activity or local infusions of endogenous vasoconstrictor substances. In the present study we have assessed the effects of three endogenous vasodilators; acetylcholine, bradykinin and histamine on lymphatic vessel contractility. Each one of these agents, when infused intralymphatically, produced lymphatic constriction as evidenced by significant increases in lymphatic perfusion pressure. The threshold concentrations which produced lymphatic constriction were between 10(-6) and 10( 5) molar for acetylcholine and bradykinin and between 10(-5) and 10(-4) molar for histamine. Surgical exclusion of the lymph nodes and efferent lymph vessels from the perfused tissue did not significantly affect the observed response, indicating that the response occurs predominately in the prenodal segments of the lymphatic system. Infusion of acetylcholine and bradykinin into the arterial supply to the forelimb did not significantly alter lymphatic perfusion pressure, unlike the response seen when catecholamines are infused intra-arterially. Histamine displayed an unusual property in that it constricts lymph vessels upon initial administration but was thereafter completely ineffective. Constriction of lymphatic vessels by substances which are potent vasodilators clearly indicates that significant functional differences exist in endothelial cell/smooth muscle relationships between blood vessels and lymph vessels. PMID- 2099388 TI - CGRP-mediated changes in segmental resistances in the canine forelimb. AB - Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide which is found in high concentrations in the perivascular nerves innervating the resistance vessels of the peripheral circulation. In the current study we have infused CGRP at three infusion rates (.01, .1 and 1.0 micrograms/min into the brachial artery for thirty minutes at each infusion rate) in the isolated, innervated canine forelimb perfused at natural flow. We measured large artery and vein pressures, small artery and vein pressures and blood flows in both the skin and skeletal muscle circulations for the calculation of total and segmental (large artery, small vessel and large vein) vascular resistances. Infusion of the lowest dosage of CGRP produced slight vasodilation in some animals but did not significantly alter the mean resistances of all the animals as a group. The middle dosage resulted in a 55% decrease in total forelimb resistance and a small but significant decrease in systemic arterial pressure. The highest dosage of CGRP resulted in a 65% decrease in total forelimb resistance and a 34% decrease in systemic arterial pressure. The decreases in forelimb resistances were equally distributed between skin and muscle and were manifested in both large artery and small vessel resistances. The potent vasodilatory effects of CGRP and its concentration in perivascular nerves innervating the resistance vessels of the peripheral circulation suggests a potential role for CGRP in control of circulatory function under normal and/or pathophysiological conditions. PMID- 2099389 TI - [Effect of a participatory method on nutrition education in dentistry]. AB - Based on results of a diagnostic test which measured the knowledge that University of Chile students of 5 different health careers have a food and nutrition (1982), the nutrition program of the school of Dentistry was modified from a traditional system of education (formal classes) to a participative methodology in 1984, a didactic material on nutritional recommendations. An increased level of knowledge as well as motivation was observed in those graduating in 1984, particularly the area of nutritional recommendation and diet, to which the students spent more extra time. We can conclude that the educational methodology that stresses participation and is centered around one person is very effective to teach nutrition in the school of Dentistry. PMID- 2099391 TI - [Comparative study of radiographic techniques for the temporomandibular joint]. PMID- 2099390 TI - [Vertical dimension of the lower facial third in frontal facial examination]. PMID- 2099392 TI - [Prevalence of bruxism in 5-7-year old students]. PMID- 2099393 TI - [Review of the treatment of decreased vertical dimension]. AB - The decreasing of vertical dimension, specially in extremely cases (more than three clinical standard deviations) is a border problem between orthopedics, orthodontics, prosthetics and surgery. The authors reviewed the treatments possibilities proposed by the different specialties. PMID- 2099394 TI - [Subperiosteal mandibular implant. Clinical cases and microscopic study]. AB - Subperiosteal surgical Vitallium implants have been set in the mandible of patients with loss of height of the osseous ridge and difficulty in the use of prostheses obtaining very good clinical and radiographical results. The optic microscopy showed a great tendency of adhesion of the gingiva's junctional epithelium to the implant. PMID- 2099395 TI - [Undifferentiated carcinoma of the maxillary sinus. Clinical case]. AB - A poorly differentiated squamous cell carcinoma arising in the left maxilla of a seventy year-old female is reported in the present paper. The patient was seeking treatment for a maintained nose bleeding which appeared several days before. In addition to the report of the clinical case, the authors rewied the main features of the disease, emphasizing the low frequency of the condition, as compared to other neoplasic involvement arising in the head and neck. Due to the advanced stage of the case herewith reported, the patient underwent no treatment. PMID- 2099396 TI - [Improvement in oral health in developing countries]. AB - The comparison of caries prevalence and of strategies applied for health promotion and caries prevention among industrialized countries, shows that systemic fluoride is the most effective method to reduce this disease. The analysis of the improvement in oral health services delivery, done through the study of the New Zealand Oral Health Care System during the period 1921-1982, confirms that this strategy, by itself, cannot produce a significative improvement in the oral health status. The review of the strategies applied to reduce periodontal disease, leads to the conclusion that the control of this disease will only be possible through health education programs with a public health approach. The study of the factors that have contributed to the decrease in oral health status in developing countries, shows that the increase in stimulous towards sugar consumption has had a great influence in the change of eating habits thus, in caries incidence. The oral health beliefs and values of the population, exercise a negative influence in the individuals health seeking behaviours. The conclusion is that it is not possible to revert the oral health status trends in developing countries, unless health promotion and disease prevention policies are implemented at government level. PMID- 2099397 TI - [100 years of the Vienna University Dental Clinic]. PMID- 2099398 TI - Cytogenetics and molecular analysis in chronic myelogenous leukemia patients treated by interferon and chemotherapy. AB - A new combination regimen including chemotherapy and interferon was started in 1986 for the treatment of 24 chronic myelogenous leukaemia patients in chronic phase. Complete cytogenetic remission were noted in 10 patients and 6 of them are in sustained remission. The overall survival was 70% at 40 months. However, a minimal residual disease was detected in the 3 patients tested with the polymerase chain reaction. In addition no correlation was detected between the site of the breakpoint and response to therapy. PMID- 2099399 TI - Matched unrelated bone marrow transplants. Results from the French group (GEGMO). AB - From a bank of 50,000 HLA typed French bone marrow donors, 125 transplants have been performed since 1986, with HLA AB and DR--identical MLC--negative donors. The median age was 25 years and the diagnosis was CGL in 59 cases, ALL in 22 cases, AML in 17 cases, SAA in 7 cases, inborn errors in 7 cases and others in 13 cases. Most of the patients received a standard conditioning regimen according to their diagnosis. The prophylaxis of GVHD was methotrexate and cyclosporine A in 77 cases; in addition to this combination 44 patients received an anti-IL2 receptor monoclonal antibody from day +1 to day +28. There was no difference between the two groups as regards the incidence and severity of GVH or survival. The actuarial survival was 36% with a median follow up of 300 days. Unlike matched sibling grafts, the usual prognostic factors such as stage of disease or age were not found to significantly modify the incidence of GVHD, which was 75%. The results of matched unrelated donor transplants are reasonably good, but must be improved by a better selection of donors and better prevention of GVHD. PMID- 2099400 TI - Prognostic factors of acute non lymphoblastic leukemia in children and adults. Results from two multicentric trials (705 patients). AB - 705 children and adults patients with de novo acute nonlymphoblastic leukemia were entered from 1981 to 1989 into 2 prospectives multicenter trials: 01AM81 and 01AM86. They received an intensive induction course with Rubidazone 200 mg/sqm/day x 4 days and cytosine arabinoside 200 mg/sqm/day x 7 days, then 3 consolidation courses at outpatients, and a maintenance treatment. Total duration of therapy was 3 years. The overall complete remission rate was 80%. The median overall survival time was 19 months and the 5-year survival rate is 26%. The median remission duration for the 568 remitters was 18 months and the 5-year first remission rate is 30%. Prognostic factors for the remission rate were age, initial leukocytosis, FAB subtype. Prognostic factors for remission duration were the delay until CR, initial leukocytosis and karyotype. PMID- 2099401 TI - Optimizing medical practice using a computerized hospital information system. Example of blood transfusions. AB - The recent focus on medical risks and dollar cost of blood transfusion has resulted in the need to define guidelines for transfusion of blood products. In 1987, a computerized knowledge-based system was implemented at LDS Hospital to screen transfusion requests and flag those not justified by criteria defined by the medical staff. The use of red blood cells (RBC) for the 9 month period from July 1, 1988 was reviewed. The number of units ordered that met the criteria used by LDS Hospital was 90%. Our results showed there was a need to refine knowledge about transfusion therapy to help physicians optimize the use of blood products. PMID- 2099402 TI - The experience of the French Cooperative Group in the treatment of CLL. AB - This paper summarizes results from clinical trials of the French Cooperative Group in chronic lymphocytic leukemia, CLL 80 and CLL 85 protocols. These protocols were based on the (A, B, C) classification. Nine hundred and seventy three patients were randomised in the CLL 80 protocol, 612 in stage A, 289 in stage B and 72 in stage C. Results from the fourth interim analysis were (1) in stage A, overall survival was better in the untreated group as compared to patients treated by daily chlorambucil with an increased incidence of epithelial cancers in the chlorambucil group; (2) in stage B, there was no improvement in overall survival with the COP regimen as compared to daily chlorambucil; (3) in stage C, the effectiveness of the CHOP regimen was confirmed. More than 1,400 patients have been randomised in the CLL 85 protocol but results from the first interim analysis were only available in stage B (194 patients). At the 6-month evaluation 28% reached complete remission in the CHOP group versus 12% in the chlorambucil-prednisone group. More follow-up is needed to assess the benefit from the CHOP regimen in terms of survival in stage B patients. PMID- 2099403 TI - A further characterization of B-CLL lymphocytes: phenotypic and functional studies. AB - The CLL-B lymphocytes are characterized by the surface expression of B cell markers (CD19, CD20, HLA-DR) and of a low intensity IgM. The presence of T antigens (CD5, CD1) may be related either to the activation stage of these cells, either to their origin from a distinct B subset. In contrast, the detection of B5, CD25, CD71 and CD38 activation markers clearly demonstrated that the B-CLL lymphocyte is a preactivated or activated cell, at various phases of the cellular cycle. Functional studies revealed that B-CLL lymphocytes are susceptible to the effects of several interleukins (BCGF(s), IL2, IFN alpha). The inhibition of the response to IL2 by IL4 has important implications for the potential use of cytokines in the management of B-CLL patients. PMID- 2099404 TI - Evidence that the B lymphocyte proliferating in B-CLL and in other B-cell malignancies is frequently committed to production of natural autoantibodies. AB - Autoreactive B-cells constitute a substantial part of B-cell repertoire. They frequently secrete polyspecific natural autoantibodies which are the expression of germinal genes. During recent years, considerable evidence has accumulated indicating that autoreactive B-cells frequently undergo malignant transformation. This evidence arose from the study of monoclonal immunoglobulins (MIgs) and from recent studies of chronic lymphocytic leukemia (CLL) and non Hodgkin lymphoma (NHL) B lymphocytes. The present review, includes two sections. The first one reviews evidence supporting the idea that autoreactive B-cells constitute a substantial part of autoreactive B-cell repertoire. The second one is devoted to review evidence favouring the view that this autoreactive B-cell repertoire is frequently involved in B-cell malignancies. PMID- 2099405 TI - Methodological aspects of a clinical trial in chronic lymphocytic leukemia: necessity to develop new biostatistical methods. AB - The CLL protocol allowed a better understanding of the natural history of Chronic Lymphocytic Leukemia and an assessment of several treatment strategies. From the point of view of biostatistical research, it raised several important problems. In this paper, we show the interest of applying sequential methods, particularly the triangular test. Other biostatistical problems raised by the CLL 80 protocol are still not, or only partially, resolved. They include taking into account prior belief about treatment benefit in sample size calculations, using surrogate endpoints, developing methods to take into account the causes of death, to analyse repeated measurements, and to assess and compare staging systems. PMID- 2099406 TI - Role of HLA class II molecules expressed on hematopoietic progenitor cells. AB - The fixation of monoclonal antibodies (MoAb) to the molecule HLA-DR induced an augmentation of thymidine uptake by bone marrow cells, an increased formation of granulo-monocytic colonies and the activation of membrane phospholipase C (PLC) in hematopoietic progenitor cell (HPC) population. The molecule DR expressed on HPC is therefore implicated in signal transduction leading to hematopoietic differentiation. PMID- 2099407 TI - Utilization of two different T cell receptors by T cell acute lymphoblastic lymphoma and leukemia. AB - We show further differences between two clinically related entities, T cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), by using several monoclonal antibodies (mAb) reacting either with constant or variable regions of T cell receptors (TcR) alpha beta and gamma delta or with various CD molecules. We analysed a panel of 15 T-ALL and 15 T-LL selected for their cell surface expression of the CD3 molecules. The results indicate that TcR gamma delta is more frequently used than TcR alpha beta in T-ALL (10 out of the 15 patients tested). This is in contrast to the results obtained with T-LL where the vast majority expressed TcR alpha beta (13 out of the 15 patients). These findings suggest that the leukemic cells could have a different origin in these two diseases. In addition analysis of TcR variable regions expressed by the leukemic blasts showed that in most cases they had rearranged functional V delta 1 gene segments (8 out of 11 patients) whereas in a unique case V delta 2 gene segment was used. Taken together these results and those indicating that T-ALL cell coexpress the CD1a,b and c molecules strengthen the possibility that even though these leukemic cells express the CD3-TcR complex at their cell surface their normal counterparts are not found in peripheral blood. PMID- 2099408 TI - Rearrangement and expression of the p53 gene in myelodysplastic syndrome and acute myeloid leukemia. AB - We performed Southern blot analysis of the p53 gene in 62 patients (37 de novo myelodysplastic syndromes (MDS), of which 10 were studied after progression to acute myeloid leukemia (AML); 14 MDS secondary to chemo or radiotherapy; 11 de novo AML). Thirteen of the 56 patients studied cytogenetically had monosomy for the short arm of chromosome 17 and, in another patient who had secondary MDS, a translocation involving a breakpoint in 17p13 where the p53 gene was mapped was found. This patient was the only individual in whom a rearrangement of p53 DNA was seen. Sixteen of the 62 patients were studied by Northern analysis, and reduced or undetectable 2.8 kb p53 transcript was found in 6 of them, who had predominantly monosomy for 17p or chronic myelomonocytic leukemia. Rearrangements of the 53 gene, identifiable by Southern analysis, are a rare finding in patients with MDS and AML, even in those with monosomy for 17p, but reduced expression of the p53 gene is relatively common. We are currently trying to detect point mutations of the p53 gene by PCR technology especially in patients with monosomy for 17p. PMID- 2099409 TI - Response of hematopoietic precursor cells to hematopoietic growth factors in the myelodysplastic syndromes. AB - The in vitro effects of 4 recombinant hematopoietic growth factors on myelodysplastic syndrome cells from 22 patients were assessed by colony assays (CFU-GM, BFU-E). DNA synthesis, cytological and cell phenotypic studies. Growth factors seemed to be potent stimulators on cell proliferation, but showed only limited effects on cell differentiation. Combinations of factors were more efficient than factors used alone. Nevertheless, culture growth patterns remained abnormal. Cell proliferation was major in the cases with excess of blasts with, in 2 cases, stimulation of leukemic cells. PMID- 2099410 TI - Involvement of granzyme B and perforin gene expression in the lytic potential of human natural killer cells. AB - Natural killer (NK) cells (CD3- LGL) spontaneously kill K562 targets but are unable to kill Daudi cells in the absence of IL-2 stimulation. IL-4 is reported to prevent or inhibit the IL-2 driven lymphokine activated killer (LAK) generation in NK cells. Therefore, we asked whether the antagonistic effect of IL 4 on the IL-2 induced LAK activity might regulate the expression of genes encoding proteins involved in lysis, like perforin the pore-forming protein or associated to lysis like granzymes A and B. By using in situ hybridization we show that, besides inducing LAK activity, IL-2 stimulation increases the amount of perforin and granzyme B mRNA at the single cell level in 40 to 100% of the total CD3- LGL population, which suggests the preferential implication of a cell subset within the LGL population. In addition, our results indicate that the stimulatory effect of IL-2 can be down-regulated by IL-4 with respect to both LAK activity and granzyme B and perforin gene expression. Here again one can notice a decrease in the amount of specific mRNA per cell. These findings suggest that the modulation of the lytic machinery via lymphokines might be associated to the regulation of the lytic potentiality of NK/LAK cells. PMID- 2099411 TI - Application of serum-free liquid bone marrow cultures to bone marrow purging for autologous bone marrow transplantation in acute lymphoblastic leukemia. AB - We have previously established a serum-free (SF) culture medium which allows normal haematopoietic progenitor cells to be maintained for at least 4 weeks as in the conventional serum dependent SD) medium. In the present study we investigated the efficiency of the SF liquid system to sustain normal residual haemopoiesis to the detriment of the leukemic population in patients with ALL. Probes for a potential selective effect were brought through leukemic progenitor cell assay (CFU-ALL) and the polymerase chain reaction (PCR) study of the bcr/abl translocation. In 13 experiments done in 12 patients, morphological blast cells and the ALL-CFU were dramatically reduced within 3 weeks of incubation in both SF and SD cultures. In 5/5 experiments in SD conditions and 2/5 experiments in SF conditions, leukemic cells expressing the bcr/abl fusion gene also disappeared within the same period. There was no difference in the CFU-GM production between SF and SD mediums. Erythropoiesis exhibited a slower decline in conditions SF, compared to the conditions SD. These results indicate that the liquid marrow culture may selectively deplete the leukemic lymphoblastic cells and enable repopulation by residual normal hemopoietic cells. It may be useful to purge leukemic cells for clinical autologous bone marrow transplantation in patients with ALL. PMID- 2099412 TI - Quinine circumvents the doxorubicin resistance of a multidrug resistant human leukemic cell-line, K562/DXR. AB - Reversal of multidrug resistance (MDR) has been obtained in vitro by a variety of agents but clinical use of these resistance modifiers is hampered by their own toxicity. Quinine, the natural isomer of quinidine, is demonstrated to circumvent doxorubicin (DXR) resistance of an MDR human leukemic cell-line, K562/DXR. In culture medium, quinine (5 mu/ml or more) significantly increases cytotoxicity and accumulation of DXR in the resistant cells but not in the parental sensitive cells. When quinine is administered by continuous intravenous infusion in the doses conventionally used in chloroquino-resistant malaria (30 mg/kg/d), serum levels reach 8-11 micrograms/ml without prohibitive toxicity. Sera from quinine treated patients enhance DXR uptake in K562/DXR cells in dose-dependent fashion. The conditions for the safe use of quinine as an MDR modifier in the treatment of refractory human hemopoietic malignancies are defined. PMID- 2099413 TI - Inhibition of platelet activation by the nitrate Sin-1: studies with human aequorin-loaded platelets. AB - The effects of the nitrovasodilator Sin-1, which is thought to work through cyclic-GMP, were studied using human, aequorin-loaded, washed platelets. Changes in light transmission (shape change, aggregation), and in intracellular calcium were simultaneously recorded. Evidence was obtained for an inhibitory effect distal to calcium changes, in a similar way than a prostacyclin analogue, Iloprost. By contrast the response to an activator of protein kinase C was unaffected. There was a partial, parallel decrease in calcium changes and aggregation induced with thrombin, and a total inhibition of the responses to ADP (linked to a calcium influx). PMID- 2099414 TI - Increased monocyte procoagulant activity in patients with systemic lupus erythematosus. AB - Monocytes can play a role in the activation of coagulation via increased procoagulant activity (PCA). We investigated the level of monocyte PCA in 19 patients with systemic lupus erythematosus (SLE), given the high rate of thrombotic events in this condition. 9 of these subjects also presented the lupus anticoagulant (LA). The PCA generated by patient monocytes was significantly higher than control values and was identified as tissue factor-like. Serum from both groups of patients (i.e. SLE and SLE + LA) stimulated the generation of PCA by control monocytes. By contrast, purified IgG from both patient groups had the same effect as control IgG on PCA generation by control monocytes. The nature of the stimulating agent in the serum was not identified. In conclusion, increased monocyte PCA may account for the increased incidence of thrombosis in SLE patients, although other, superimposed, factors would appear to exist in SLE + LA patients, given the higher incidence of thrombosis in this subgroup. PMID- 2099415 TI - Postgraduate medical education and clinical tutors--the way forward. PMID- 2099416 TI - Helicobacter pylori--our knowledge is growing. PMID- 2099417 TI - Competitive sport and the insulin-dependent diabetic patient. PMID- 2099418 TI - Infection and infectious diseases. PMID- 2099420 TI - Endobronchial tuberculosis--is corticosteroid treatment useful? A report of 8 cases and review of the literature. AB - Eight patients with endobronchial tuberculosis diagnosed on bronchoscopy were treated with antituberculosis drugs and a course of prednisone. The progress of the endobronchial lesions was assessed on repeated examinations. The course of the disease was variable and the endobronchial narrowing improved in two patients only. Hypersensitivity reactions associated with initiation of antituberculosis treatment may constitute a special group where corticosteroid is indicated. In other situations, the usefulness of corticosteroid for treatment of endobronchial tuberculosis is not well documented. PMID- 2099419 TI - Emotionalism following brain damage: a complex phenomenon. AB - Emotionalism is a common and distressing consequence of many forms of brain damage. There is uncertainty about its classification, aetiology and treatment. A commonly used typology is difficult to apply in practice as illustrated by three clinical examples. We describe the various components of emotionalism and highlight their range and variability. In future research each component should be examined in detail using a standardized form of assessment. PMID- 2099422 TI - Intracavernosal metaraminol for treatment of intraoperative penile erection. AB - Four patients developed penile erection when regional anaesthesia was induced with spinal block. In another patient, penile erection developed during fentanyl induced general anaesthesia. Injection of metaraminol into corpus cavernosum successfully achieved detumescence in all these patients. The dose of metaraminol ranged from 10 to 25 micrograms, much less than that required for the treatment of vasodilator-induced priapism. Intracavernosal injection of metaraminol is a simple, effective and safe method for immediate relief of intraoperative penile erection. It is most useful when urogenital operation would be delayed by penile tumescence. PMID- 2099421 TI - Danazol in non-splenectomized patients with refractory idiopathic thrombocytopenic purpura. AB - Seven non-splenectomized patients with chronic refractory idiopathic thrombocytopenic purpura were treated with danazol 800 mg daily. All were glucocorticoid failures and four were refractory to all additional previous therapy. Five patients benefited from danazol and in two sustained normal platelet counts, for over 44 and 51 months, were observed. We conclude that danazol is useful for long term management of otherwise refractory idiopathic thrombocytopenic purpura. The advantage of danazol over splenectomy as a first line treatment in steroid failure is suggested. PMID- 2099424 TI - Torsion of an accessory spleen in an elderly patient. AB - Torsion of an accessory spleen is recognized as a rare cause of acute abdominal pain in childhood. A case is reported which, however, is unusual in that it occurred in a patient of 75, who had had no previous symptoms which might have suggested the presence of an accessory spleen. PMID- 2099425 TI - A calcified thoracic mass. PMID- 2099423 TI - Mitral valve prolapse and occult aortic coarctation. AB - A 22 year old man developed symptoms of left ventricular failure secondary to atrial fibrillation and congenital mitral regurgitation. After operation for mitral valve repair he was unable to be successfully weaned from cardiopulmonary bypass and this was ascribed to poor left ventricular function. He therefore underwent emergency cardiac transplantation but again was unable to be weaned from bypass. At post-mortem examination a previously undiagnosed aortic coarctation was revealed. The presentation of occult aortic coarctation is discussed, and its association with congenital mitral valve abnormalities reviewed. PMID- 2099426 TI - An unusual cause for a fit. PMID- 2099427 TI - The responsibilities of Health Authorities for medical education--an open letter to deans and clinical tutors in light of impending changes to the National Health Service. PMID- 2099428 TI - Continuing medical education for general practitioners in North Devon. AB - The establishment of a continuing medical education system for established Principals in a semi-rural area is described. The essential requirement is a 'link man' in each general practice in the area. Clinical tutors, course organisers and regional advisers are all actively involved to produce a regional educational policy. PMID- 2099429 TI - Concomitant euthyroid Graves' ophthalmopathy and isolated ocular myasthenia gravis. AB - A 44 year old diabetic woman presented with diplopia and bilateral ptosis and mild exophthalmos. The patient was clinically euthyroid, the baseline thyroid function tests were normal, but the thyroid stimulating hormone response to thyrotrophin releasing hormone was flat. Computed tomographic scan and magnetic resonance imaging of the orbits showed left medial and inferior rectus muscle thickening, more prominent on the left side, consistent with Graves' disease. The tensilon stimulation test resulted in resolution of the ptosis and partial improvement of the ophthalmoplegia. The single fibre electromyography was consistent with a defect in neuromuscular transmission. However, forced duction test was normal and anti-acetylcholine receptor antibodies were undetectable. Significant improvement of the extraocular muscle function and resolution of the right ptosis had resulted from anticholinesterase therapy. These findings and the clinical response to therapy were consistent with concomitant euthyroid Graves' ophthalmopathy and ocular myasthenia gravis. Coexistent isolated ocular myasthenia gravis and Graves' ophthalmopathy is rare and should be considered in patients with findings of ocular myasthenia and extraocular muscle dysfunction. PMID- 2099430 TI - Multiple sclerosis associated with trismus. AB - This report describes the case history of a middle-aged lady who presented with symptoms and signs over one year leading to a diagnosis of multiple sclerosis. During one of her relapses, she developed trismus--an association that has not been described before in multiple sclerosis. PMID- 2099431 TI - Anticoagulation instability with life-threatening complication after dietary modification. AB - Anticoagulation instability due to a change in intake of vitamin K after dietary modification was observed in 2 patients on long-term oral anticoagulants. One patient developed diffuse bruises treated conservatively with fresh frozen plasma transfusion and the other had a thrombosed aortic prosthesis which required emergency operation. To prevent such complications, dietary modification especially with food rich in vitamin K should be undertaken with care in patients on long-term oral anticoagulants. PMID- 2099432 TI - Anaphylactic reactions to topical antibiotic combinations. AB - We describe two patients who developed anaphylaxis type reactions following the application of the topical antibiotic Polyfax (polymixin B and bacitracin). We draw attention to this potentially serious complication of topical antibiotic preparations and emphasize the need for careful history taking before prescribing such preparations. PMID- 2099433 TI - Spontaneous iliopsoas haemorrhage--an unusual complication of streptokinase therapy. AB - We report a case of spontaneous iliopsoas haemorrhage following intravenous streptokinase which serves to remind physicians of the potential dangers of this form of therapy. PMID- 2099434 TI - Bleeding oesophageal varices associated with anabolic steroid use in an athlete. AB - A 30 year old bodybuilder who had been taking anabolic steroids for 18 months presented with bleeding oesophageal varices. Serious liver disease secondary to anabolic steroids including peliosis hepatis, nodular hyperplasia and malignant change is well recognized. We report what is, to our knowledge, the first case of bleeding oesophageal varices associated with the use of anabolic steroids. PMID- 2099436 TI - Primary renal ganglioneuroblastoma in an adult. AB - A rare case of primary renal ganglioneuroblastoma in a 68 year old female is presented. The authors believe this to be the first case report of this tumour arising in the kidney of an adult patient. PMID- 2099435 TI - Peritoneal mesothelioma. AB - We report two patients who presented with small bowel obstruction secondary to peritoneal mesothelioma. The difficulties in establishing this diagnosis at an early stage are illustrated. Recent advances in the management of peritoneal mesothelioma are reviewed. PMID- 2099437 TI - Small bowel obstruction with multiple perforations due to enterolith (bezoar) formed without gastrointestinal pathology. AB - An enterolith (bezoar) usually originates in an intestinal diverticulum or in a segment of bowel loculated by stricture formation. Stasis promotes its formation. This communication describes a case in which a large enterolith caused obstruction and multiple perforations of the terminal ileum in the absence of any predisposing gastrointestinal pathology. The management of this rare occurrence is discussed and the literature reviewed. PMID- 2099438 TI - Small bowel infarction associated with pancreatic glucagonoma. AB - An 88 year old woman presented comatose, hypothermic and hyperglycaemic. She died soon after admission and at autopsy recent small bowel infarction was found. The superior mesenteric artery was encased in a dense pancreatic mass and there was marked luminal narrowing of the vessel. Histology revealed a pancreatic glucagonoma which had metastasized to colonic submucosa and serosa. Glucagonoma is a rare tumour and this presentation of small bowel infarction associated with pancreatic glucagonoma would appear to be a unique event. PMID- 2099439 TI - Spontaneous rupture of the spleen in Legionnaires' disease. AB - A case of Legionnaires' disease is described in a 63 year old man who presented with pneumonia and confusion. Eleven days after admission he became acutely hypotensive and attempts at resuscitation failed. Post-mortem examination revealed spontaneous splenic rupture and massive hepatocellular necrosis--an outcome that has not previously been associated with Legionnaires' disease. PMID- 2099440 TI - Common bile duct gallstones; anicteric presentation in the elderly--under recognized but important. PMID- 2099441 TI - Diaphragmatic paralysis: a difficult diagnosis. PMID- 2099442 TI - 'Spread-eagle' position for the rectal examination of the prostate. PMID- 2099443 TI - [The metal content of natural waters]. AB - The authors give the results of their studies for the presence of metals in waters. The investigations are carried out in two directions; the first is related to the solving of pure analytical problems, the second--to the behaviour of the metal ions in water media and hygienic evaluation of their level. Several variants of atomic absorption spectrometry (AAS) are comparatively studied: by flame--directly and by means of extraction concentration and without flame AAS- with and without matrix effects. The analytical parameters of the mentioned methods are determined as well as the experience of their use according to the expected concentration of metals and type of waters. It is established that the content of metals in underground waters is comparatively lower and with no seasonal, local and regional differences. The presence and concentrations of the latter in surface waters is affected by the anthropogenic factors and show a tendency towards fluctuation in type and place. It is also proved that metals have different behaviour in the water media stimulating a diverse tendency towards distribution between water phase, suspending material and bottom sediments. PMID- 2099444 TI - [Derivative spectroscopy and its use in sanitary hygiene control]. AB - An analytical method is developed for defining the residual quantities of rodenticide "Brodifacoum" (talon) used in the control of harmful field rodents and especially for species Microtus. The method is based on extracting the pesticide with chloroform and making use of spectrophotometry in the ultraviolet field in intervals 340-240 nm. The second derivative of the absorption is utilized as well as the band with maximum 288 nm and minimum 228 nm. The peak height in this interval is in proportion to the concentration of the brodifacoum. When analysing residual waters, reservoirs, and soil the elimination of impeding substances is performed by thin-layer chromatography. The "cis" and "trans" form of brodifacoum is jointly determined by spectrophotometry. At thin-layer chromatography processing the two forms are separated. Sensitivity of the method 0.5 microgram/cm3 (in chloroform solution). Reproduction (as coefficient of variation) 5%. A thin-layer chromatographic method is recommended for semiquantitative determination of brodifacoum. PMID- 2099445 TI - [Dust levels and dust-induced diseases in the main dust-producing industries]. AB - The data on airborne dust and occupational disease in the main dust-related industries of the People's Republic of Bulgaria are generalized and analyzed for a period of 15 years. In the ore producing industry is established a stability in the concentration of total and respirable dust 1-2 TWA concentrations and decrease of silica content in dust. The highest occupational hazard is registered in diggers. The levels of TWA total and respirable dust and silica concentrations in the other underground mines as well as in the overground industries are strongly variable and high. Silicosis is still in the first place among dust related diseases, but mainly among miners of advanced age. The newly detected other pneumoconiosis, asbestosis, mixed pneumoconiosis are already more than the cases of silicotuberculosis. An essential part is taken by the newly detected diffusive pneumosclerosis and dust bronchitis. The distribution of the newly detected occupational lung diseases is studied according to branches of industry. PMID- 2099446 TI - [The mycotoxicological and dust contamination of the air in plants for the preliminary processing of cotton and hemp]. AB - Investigations are carried out in two enterprises for primary processing of cotton and one - of hemp. On the working places were determined dust concentrations on the technological lines and the mycotoxicological pollution of the air. Examinations were made on the workers. Concentrations above the norm were established of total dust and high rate of concentration with microbes and spores of microscopic fungi from the families Cladosporium, Alternaria, Aspergillus, Penicillium and Fusarium. The proved toxic and allergenic effect of the microflora and the high concentrations of the dust are prerequisites, which impose a reevaluation of the approaches to hygiene standardization of dust from natural textile fibres. Thus the prophylaxis of occupational diseases of a large contingent of workers will considerably improve. PMID- 2099447 TI - [A fluorescent method for the quantitative determination of germanium in the air of a work environment]. AB - The method is based on the fluorescent measurement of the product, of its reaction to morin in strong acid medium. The sensitivity of the method - 0.02 mg in the analysed sample and the accuracy, expressed by the coefficient of variation - 17.7%, show that the latter is adequate for the purposes of chemical and hygiene control on the air of the working environment. The presence of aluminium, beryllium, lead, potassium in the examined air don't stand on the way of determining the concentration of germanium. PMID- 2099448 TI - [The effect of instruction with computers on the functional state of first graders]. AB - A study is carried out on 64 first grade school children for establishing the effect of computer training on the functional status of principally engaged systems with the purpose to determine the optimum duration of work with video terminal during the school day. The examinations are performed before and after computer lessons in mathematics and Bulgarian language in days with one and two lessons, and with the same subjects taught in the traditional way (control group). Traced are the changes in the accommodation, the eye rheobase, critical frequency of fusing the light flickers, resistance, volume and accuracy of the visual perception, static tremor and excretion of sodium and potassium in the saliva. The data point out to relatively higher pressure at work on video terminal in comparison with the traditional education. This imposes restriction in the duration of the lesson up to 20 minutes. The inclusion of second inconsistent computer lessons in the educational programme has no unfavourable effect on the functional status of the organism. PMID- 2099449 TI - [The evaluation of the adaptation of pupils starting instruction at 6 years old to new academic programs by using a computer analysis of cardiac variability]. AB - Examination of the pulse variability of 6 years old (experimental group) and 7 years old control group schoolchildren is performed for establishing their adaptation capability to the educational process at the end of VI and VII class. 76 schoolchildren are comprised in the investigation. The analysis of the pulse variability is made on the basis of 10 min. ECG record on telemeter "Biomedica". A computer processing is made on the records by complex programmes for receiving indices related to the statistical characteristic of the dynamic order of cardiac intervals and to such giving their distribution. The receiving statistically significant differences for most of the indices between both groups of schoolchildren from VI class show an expressed activation of the adrenergic mechanisms with EG as well as higher "physiological value" of adaptation to the educational process. In VII the class the indices of the heart variability with EG practically show no differences from those of CG. This ascertainment proves, that at the age of 13 the potentialities for studies of those children starting school at 6 years are compensated with the children starting school at 7 years. This imposes the studies and the organization of the educative process for both 6 and 7 years old schoolchildren to be taken into consideration, to the completion of 7th class, with their age adaptive potentialities. PMID- 2099450 TI - [The occupationally important qualities of adolescents studying for the job of power engineer-operator]. AB - Investigation is made and data given for the rising generation from III and IV class trained for the specialty "operator-power technician". Studies are carried out on a number of properties of the Central Nervous Activity and the analyzers, some functions of attention, as well as specific personal characteristics of 44 professionally suitable and 21 professionally unsuitable schoolchildren. The results of the comparative analysis of the experimental material, and the received correlation relation of the incidences with the external criteria "success in the mastering of the profession" give grounds to accept that the high versatility of the basic nervous processes, the capacity for concentration, resistance and swiftness in switching the attention, the low personal uneasiness and expressed emotional stability are of professional importance and determine the possibility for success in mastering the profession "operator-power technician". PMID- 2099451 TI - [Problems of the health status of the youth from a student town]. AB - Studies are carried out on the health status and morbidity of students from the territory of the student town and health-hygienic undertakings are recommended for improving the health of the students and formation of health habits. For 8000 students were traced the following data: prophylactic examinations, acute morbidity, morbidity according to medical registrations studied from the statistical cards, the follow-up care of patients with chronic diseases. A scientific statistical method for studying the medical documentation is used for examining the acute and chronic morbidity. The basic moments in the structure of the students pathology are described, stimulated by the new moments of life in the conditions of the students town and the peculiarities in the health status of the students as special age group of the population. Conclusions are made concerning the carrying out of directed hygiene-preventive undertakings. PMID- 2099453 TI - [Biphasic allergic reactions in occupational bronchospastic diseases]. AB - Allergological examinations are made on 79 workers (skin tests and inhalatory provocation) in contact with textile, wood and flour dust which complained of fit or permanent asthma. At skin testing 24 of 79 workers show positive early and late reaction, and 6--only positive late reaction. At inhalatory provocation 32 persons are positive at least to 2 indices of late reaction. The two-phase reaction of sensitivity to occupational allergens are frequent phenomenon in individuals with bronchospasm, because of the complex character of the occupational allergens and the generated by them immune responses. As a rule the late skin reactions are combined with delayed allergy at inhalatory provocation. In some cases a late allergy of III and IV type is established with exogenic alveolitis. The pathogenesis and the clinical importance of the two-phase reactions are discussed. PMID- 2099452 TI - [A method for the quantitative evaluation of the probability of ischemic heart disease in epidemiological research on workers exposed to harmful effects]. AB - A method for quantitative evaluation of the probability for ischaemic disease of the heart in epidemiological studies is recommended and the state of risk is determined by riskogram, including 3 parts: 1. Assessment of the electrocardiographic changes after Minnesota code. 2. Integral quantitative interpretation of ECG-changes with the data from the Rose test. 3. Classified quantitative assessment of the probability for ischaemic disease of the heart. The quantitative interpretation of the probability for ischaemic disease of the heart allows the use of various statistical methods, mathematical models and computer processing of data, received at the epidemiological studies. By tracing the dependences "dose-effect" and "dose-response" the maximum admissible duration of the length of service could be predicted in specific conditions of professional exposure, in order to prevent injury of the cardiovascular system from harmful industrial factors. PMID- 2099454 TI - [An economic analysis of the morbidity with temporary loss of work capacity in the electrolysis shop of a nonferrous metallurgical engineering combine]. AB - An economic evaluation is made on temporary disability because of disease of trauma, for a three-year period in one shop of technological plant for nonferrous metallurgy. The established, by means of economics-mathematical method, not produced production sums up to approximately 18 million leva. PMID- 2099455 TI - [The legal and social problems of occupational disease expertise]. PMID- 2099456 TI - [The sociomedical and legal expertise of temporary loss of work capacity]. PMID- 2099458 TI - [The effect of electrochemical silver on the microbiological qualities of drinking water]. AB - The possibilities of silver ions, received by electrochemical way, are studied for having bactericidal effect on the microflora of potable water. For this purpose are taken waters with different bacterial insemination and the effect of silver on microorganisms with different resistance is traced. Parallel to that are studied the possibilities for preservation of preliminary disinfected potable water, as well as comparative evaluation at disinfection with chlorine preparations and with silver ions. PMID- 2099457 TI - [A test for determining hydrogen sulfide in waste waters]. AB - An express quantitative test is recommended for determination of hydrogen sulfide in waste waters, based on linear colorimetric principle, which could be used for concentration scopes: 20-400 mg/l with sensitivity 10 mg/l; 10-250 mg/l with sensitivity 5 mg/l. The reproduction of the test is very good--the coefficient of variation do not surpass +/- 10%. PMID- 2099459 TI - [An approach to the study of the effect of environmental factors on human health in a population center]. AB - The prophylactic, organizing, methodic and governmental purposes of the study in the field of the settlement hygiene, given in systematic way, are put for solving the actual problem of interrelation "man-environment-health" in ecological and health-prophylactic aspect. The study directs at the correct organization of the investigations and the preventive measures at the priority of significance of the risk factors and the expected decrease in the diseases provoked by them. In order to achieve the desirable social-health effect as a consequence of the prophylactic activity, it is performed in strongly affected by the urbanization settlements as well as in such where the negative anthropogenic interference is particularly underlined. The basis of developed, developing and future formation of settlement are given in view of their arrangement according to priority of significance in the programmes for optimizing the environment and achieving the desirable ecology. PMID- 2099460 TI - [A hygienic study of new raw materials for cosmetic agents and household chemical preparations]. AB - Studies are performed on the new Bulgarian raw materials "Aminookis" (AO) and "Dezodorirashch agent" (DA) the plants "Alen Mak"--Plovdiv and "Hyaluron"--Sofia. Chemical, toxicological and microbiological studies are carried out. Thin-layer chromatographic and spectrophotometric methods for determination of AO, hyaluronic acid and DA are developed and chemical studies on cosmetics, prepared with them, are carried out. During the repetition of a 21-day experiment on guinea pigs the threshold irritative concentrations--10% for AO and DA (as trade products) are determined. This shows that they are moderate contact irritants. The hyaluron has no irritative effect. By maximizing test with guinea pigs is established the absence of contact allergy for DA and AO. At index of sensibilization 10% the hyaluron falls in the group of weak allergens. The spectra of action are studied and the minimum suppressing concentrations of AO and DA are defined. It is established that the most resistant to effect with these cosmetics are the representatives of the families: Pseudomonas, Klebsiella, Escherichia, Salmonella. Recommendations are made to use "Aminookis" (AO) in shampoos to 8%, deodorizing agent in deodorants to 2% and "Hyaluron" in creams to 20% (as trade products). PMID- 2099461 TI - [Health and hygiene research on constructive toys intended for children over 7 under natural conditions]. AB - Physiological and questionnaire investigations are carried out on 10 constructive toys, with the participation of 38 children 7 to 12 years old. A testimonial of the toys is made according to mass, dimensions, technological treatment, packing etc. A number of discrepancies with the hygienic requirements were established: 1) imperfection of the technological treatment (sharp edges, tops and holes, difficult assembling and disassembling of details, not fitting some details at construction, presence of odour, dust in the packings); 2) discrepancy with the announced age destination; 3) faults (incongruity of colours, small dimensions of models and not clear and contrast models, absence of age destination); 4) unphysiological strain and fatigue during play with part of the toys. On the basis of the results are developed hygiene recommendations to the manufacturing of constructive toys for children over 7 years. PMID- 2099462 TI - [Changes in neuropsychic activities during work in clean rooms]. AB - In clean rooms of the system of electronics are carried out work-physiological examinations on two basic professional groups--working in photolithography and operators. At the end of the workings day a considerable prolongation of the sensomotor reactions and deterioration of the dynamometric indices, characterizing the functional status of the neuro-muscular system were found. The time for performing the complex sensomotor reactions (choice of reaction) remains unchanged. At the end of the working day as a result of the performance of a considerably complex work activity, carried out in the clean rooms, was established a significant decrease in the functional state of the central nervous system and development of general and nervous fatigue. PMID- 2099463 TI - [An electroneurographic study of agricultural workers working with organophosphate pesticides]. AB - An electroneurographic method is used for examining 60 agricultural workers at the beginning and the end of the season of spraying with organophosphorus pesticides. At the end of the season (in comparison with the beginning a significant increase of the amplitude of the evoked potential is established as well as a decrease in the velocity of performance at stimulating the motor fibres of n. medianus, and in the velocity of conducting of n. peroneus. The electroneurographic method could be used with success for monitoring the effects of exposure to organophosphorus pesticides. PMID- 2099464 TI - [The neurological screening of workers in land reclamation and erosion control enterprises]. AB - Examinations were performed on the nervous system (directed anamnesis, neurological and vegetative status) of workers from enterprises for economic melioration and erosion control. The following was established: presence of vegetative vascular disturbances in the upper extremities, radicular syndromes, neurosis-like [correction of neurosimilar] syndrome, with higher frequency at the exposure of vibrations in comparison to nonexposed workers; in conditions of vibrations and noise above the norms work persons, with organic disturbances of the nervous system, which certifies for the nonobservance of the medical contraindications and for necessity of special control on these workers. PMID- 2099465 TI - [The assessment of the vibration load in tractor drivers]. AB - The assessment of the vibration loading of a group of tractor-drivers from the enterprise for melioration and erosion control is made on the basis of: measurement of general and local vibrations and noise of 5 tractors type C 100, C 100M and T 130; determination of the total vibration loading on the basis of data of measurements and average weekly hour individual engagement; comparison of the admissible values of vibration loading with the real determined at work with machines of different vibration characters at different hour engagement. A surpass of the admissible vibration loading is established which reaches up to 3.3 (at average weekly exposure to 30 hrs.) and to 4.7 hrs (at average weekly exposure 42.5 hrs.) with the tractors with higher surpass of MAC for the general vibrations. An admissible exposure for 1 day and for 1 year work for the separate tractors is determined in relation to the data for general and local vibrations and individual hour engagement. PMID- 2099466 TI - [The relationship of exposure to chemically harmful compounds and disorders of the health status in workers in ethylene production]. AB - On the basis of job characteristics of workers from the production "ethylene", chronometric studies and measurement of concentration from chemical compounds are developed professional diagrams and risk diagrams, which give a possibility for more precise account of the exposure to chemical noxious compounds (by figures). According to the values of the estimated total index of exposure 156 workers are distributed in 5 groups. Besides, 48 workers with prolonged length of service in the production and 37 persons control group are examined. The toxicological, haematological and biochemical indices are studied and the neuro-vegetative status traced. Mainly in the groups with high chemical exposure (first and second risk groups) and with prolonged length of service are established high per cent of workers with deviation in the examined indices, which give grounds to assert for the presence of dose-response relationship. PMID- 2099467 TI - [Biochemical liver studies of workers in ethylenediamine production]. AB - Studies are performed on 44 workers, engaged in the production of ethylenediamine. The principle chemical noxae are: ammonia, ethylenediamine, dichloroethane, analogues of ethylenediamine, vinylchloride, sodium hydrate etc. The average concentrations of these compounds surpass the admissible norms for the air of the working environment. The biochemical studies certify for the presence of deviations in the enzymes, detoxication and lipidic liver functions. The established changes are observed in workers with length of service in the production more than 9 years. When juxtaposing the results the following risk groups are outlined: repair-maintenance staff and technical personnel. PMID- 2099468 TI - [Epidemiological studies on the manufacture of cross-linked polyethylene]. AB - In the production of cross-linked polyethylene in the air of the working environment above the norm concentrations of acetophenon, dicumyl peroxide and antioxidant are established, which create unfavourable working conditions. During clinical and laboratory examinations of 55 workers, engaged in the production of cross-linked polyethylene, are registered subjective complaints from the irritating effect of the chemical noxae on the mucous membranes and skin. Methaemoglobinaemia is found in 4 workers. There are deviations in the functional state of the liver (transaminase, APh, GGTP and triglycerides) in the group "maintaining staff". The same workers have also increased quantity of metabolite hippuric acid in the urine. On the grounds of the results, the group "maintaining staff" is determined as risk group. Recommendations are made for follow-up care and work in controlled parameters of the working environment. PMID- 2099469 TI - [Biochemical changes in the brain tissue of white rats exposed to the herbicide acetochlor under acute and subacute oral experimental conditions]. AB - In the conditions of acute and subacute oral intoxication with acetanilidic preparation acetochlorine applied in doses respectively 1/5 LD50 for acute experiment and 1/20 and 1/100 LD50 for subacute experiment (LD50 for male animals -1063 mg/kg-1, and for females--768 mg/kg-1) are traced the changes in the capacity for methaemoglobin formation, the quantity of sulfhydryl groups in the serum, the activity of LDH, G-6-PhDH, IDH, MDH, SDH, Cyt Oxidasis and the quantity of soluble proteins in brain homogenates and isolated mitochondria of brain. The animals of the acute experiment are examined on the 1, 3, 5, 7, 10 and 14 day of the poisoning, and the animals of the subacute experiment--on the 24th hour after the last administration (42-day treatment with the preparation, 5 days weekly). The herbicide acetochlorine at unrepeated introduction of dose 212 6 mg/kg-1 (1/5 LD50) and multiple administration for a period of 42 days in doses 1/20 and 1/1000 LD50 in the stomach of white rats possess well expressed methaemoglobin formation capacity. In the conditions of acute and subacute experiment the preparation causes one-type changes in the enzymes activity, certifying for a destruction of the mitochondrial apparatus. A suppression of the activity of SDH, IDH, Cyt oxidasis and increase of the LDH, G-6-PhDH activity, could be a result of methaemoglobin formation. The latter is a predispose factor for appearing of chemical hypoxia leading to the inclusion of compensatory anaerobic oxidizing processes. The registered deviations have to be read at the hygiene standardization of the preparation. PMID- 2099470 TI - [Wire ligatures for minor tooth movement in periodontics]. PMID- 2099471 TI - [Bruxism. N.M.R.S]. PMID- 2099472 TI - [Acrobatic tongue (Ehlers-Danlos disease)]. PMID- 2099473 TI - [Proximal-occlusal cavities for silver amalgam in primary molars]. PMID- 2099474 TI - [Child in dentistry: person or puppet?]. AB - Many years ago the author introduced and advocated the comprehensive approach in pediatric dentistry. He emphasized the priority of an empatic relationship among child, mother and dentist with positive communication channels. The use of sedation, other aversive methods and even an hypertechnical attitude are only attempts to avoid the child's anxiety. Wi need him as a total person, not as a typodont. PMID- 2099475 TI - [Polymorphic erythema (P.E.)]. PMID- 2099476 TI - [Oral lichen planus: epidemiological observations in Argentina]. AB - The prevalence of the oral lichen planus and its distribution by sex, age and clinical forms was studied in population's samples and series of cases. The prevalence rates observed ranged from 0.129 to 0.38% with the highest values (0.66%) in the oldests groups of age. In the series of cases no significant differences were observed in sex distributions with increased values of prevalence, in both sexes, over 40 years of age and the highest values in the fifth decade of life. Atypical clinical forms, specially erosive forms, predominated in the series of cases but not in the population samples. Their true occurrence must be establish by epidemiological works on wider samples of people. PMID- 2099477 TI - [Pulp impressions. Their use in endodontic practice]. PMID- 2099478 TI - [Peter Camper. Historical review. The Camper facial angle]. PMID- 2099479 TI - [Some factors that affect irrigation of root canals]. PMID- 2099480 TI - [Frequency and distribution of oral lesions in elderly patients]. AB - In this study the relative frequency of oral lesions was evaluated in a group of 526 patients, 55 years old or elder. Clinical and pathological data were obtained from 244 patients who attended to a clinic of Medical and Social Assistance Program (PAMI) ad from 282 cases registered in the files of the Surgical Pathology Laboratory F.O.U.B.A. (LAP) since 1984 to 1986. The mean age of the groups was 63 years old. The most frequency lesions were the pseudotumors (44.6%) in LAP and (17.2%) in PAMI; premalignant lesions were (20.5%) in LAP, while in PAMI (2.4%). The cysts in LAP found (15.6%) in PAMI were (2.4%). The groups of PAMI showed (90%) of Candidiasis. Traumatic ulcer (30.7%) and afthae (28.8%). In LAP were (4.6%) the traumatic ulcer. The malignant tumors the most frequency was carcinoma espinocelular (8.16%) LAP and (6.56%) PAMI. It was remarkable that stomatodine as represented in PAMI (72.2%) and Candidiasis were (90%). Candidiasis were 90% of the specific inflammations. Results suggest that oral mobility in elderly patients correlates with the findings in this type of social assisted groups. The figures of the importance of methodical collaboration of Stomatologists and Oral Pathologists for differential diagnosis. PMID- 2099481 TI - [Use of elastomers (silicones) for provisional and final impressions]. PMID- 2099482 TI - [One case, two solutions]. PMID- 2099483 TI - [Extraoral accidents with endodontic rotary instruments. Report of two cases]. AB - A serious warning against the possibility of extra-oral accidents caused by endodontic mechanically driven instruments is made. Some critical characteristics of such instruments are described, as well as physical, technical, ergonomic and human reasons conducting to these accidents, two cases of which are related. Finally, colleagues are invited to think critically upon their own rhythm of labour and some preventive measures are proposed. PMID- 2099484 TI - [Oral manifestations in AIDS or HIV infection. Bibliographic update]. AB - AIDS is a systemic infection that in many steps of its evolution presents various oral lesions and clinical conditions. This fact raises a problem for the dentist who are working on heterogeneous populations of healthy and infected people as well as on AIDS patients: to receive a continuous update about the disease. Apart from the risks of exposure inherent to his personal relation with HIV-infected or AIDS patients, the dentist is one of the health careworkers who must and ought recognize the oral signs of the disease when they appear in the mouth. For this reason this paper describes recent data on oral findings in AIDS: fungal, viral and bacterial infections, neoplasms and other manifestations of unknown or rare etiology. The most precocious clinical or pathological characteristics of these oral diseases suggesting HIV-infection or its results, are also stressed when described. Some doubts are possessed here about the meaning of outstanding oral AIDS lesions as "hairy leukoplakia". On the other way diagnostic methods which can help to recognize this lesion are also commented. PMID- 2099485 TI - [Prevalence of tongue anomalies in children]. AB - The prevalence of grooved tongue, geographic tongue, and ankyloglossia, was investigated in 660 children, 3 to 13 years old, which attended the Out patient Clinic of the University Hospital of Buenos Aires for unrelated complaints. The figures obtained are at variance--by far--from those published by other people engaged in the same line of research. Probably, further studies with a much larger amount of patients are called for. PMID- 2099486 TI - [Comparative study of four methods of centric relation registration]. PMID- 2099487 TI - [Piroxicam, diazepam and placebo in the treatment of temporomandibular joint dysfunction. Double blind study]. AB - The effects of Piroxicam, Diazepam, and a Placebo on patients of different degrees of Stomatognathic System Dysfunction were studied. No statistically significant differences were found between the therapeutic effects of Piroxicam, Diazepam and a placebo. PMID- 2099488 TI - [Dental caries in an urban school population in Azul, Argentina]. AB - The Odontopediatric Service of the Azul Children's Hospital has accomplished this survey in order to know the caries prevalence in students of Azul city (Pcia. Buenos Aires) and to compare its results with a similar research done in April 1968. A group of 518 pupils attending one of the city schools were investigated in order to establish the amount of damage produced by caries in children between 6 and 14 years old. PMID- 2099489 TI - [Philosophy of extension courses in endodontics]. PMID- 2099491 TI - [Benign teratoma (teratoblastoma, teratoid tumor)]. PMID- 2099490 TI - [Neurilemmoma or benign schwannoma of the palate]. PMID- 2099492 TI - [Retraction of the gingival margin for impressions with plastic materials]. PMID- 2099493 TI - [Role of the immune system in chronic periapical disease of pulpal origin]. PMID- 2099494 TI - [Experimental study of removable partial denture retention]. AB - This article describes a series of laboratory experiences about the retentive action of different designs of free end removable partial dentures. It reaffirm the classic concept of the better efficiency of the gingival -occlusal arm clasp than the gingival-occlusal ones, the efficiency and benefits of the rough clasp and the important retention of the posterior action clasp. We find also that the classic concepts of direct and indirect retention can be reformulated, in attention than the odem retainers, such as derived from DPI conception, develops an integral concept of retention and a rational system of fixing derived of the retainer design and the abutment preparation. PMID- 2099495 TI - [Prevalence of hepatitis B virus markers in dentists in a rural community]. AB - It carried out an epidemiology serum study in dentist of Lincoln with the object to know the prevalence of hepatitis B viral index and the influence of the professional and extra-professional. From the 12 integrants of the study, 3(25%) had any positive index. There are significant differences with a group of voluntary blood donars, its considered a danger group. There aren't any difference between dentist of rural and urban community. The prevalence is increased by: the oldness in the profession, the number of patients by month, the specialty, the absence of preservative measure, the age, the sex and the antecedent contact with hepatitis. PMID- 2099496 TI - [Management of a case of iatrogenic treatment of anterior teeth]. AB - A case with unusual iatrogenia due to dental attention is introduced, as well as the first steps made to solve the situation. Some conclusions obtained from the treatment are also summarized. PMID- 2099498 TI - [Mouth protectors]. PMID- 2099497 TI - [Endodontic-periodontal relations]. PMID- 2099499 TI - [Diagnosis for osseointegrated implants]. AB - It is discussed the importance of the diagnostic, prognostic and treatment design procedures in the oral rehabilitation where osseointegrated implants are used, doing a detail of the sequence to follow during this important treatment stage. PMID- 2099500 TI - [Current clinical management with antimicrobials in periodontal patients]. PMID- 2099501 TI - [Orthognathic surgery study group. The orthodontic-surgical team]. PMID- 2099502 TI - [Function and role--a study of terminology]. AB - In order to identify what the nursing professors think about the meanings of the words Function and Role, and their use, we elaborated a formulary and applied it at a nursing educational institution of the interior of Sao Paulo. From the sample of 23 people, we observed that several words are used meaning Function and Role, and sometimes they are also used as synonymous. We also perceived that in the literature reviewed, though some authors express that Role is related to status, to behaviour and Function is activity, atribution. PMID- 2099503 TI - [Changes in life style confronted by patients with chronic health conditions]. AB - The purpose of this study was to identify the life style changes in patient with chronic illness. The sample consisted of 45 patients with chronic diseases. The findings showed that the patients had to face changes in their life Style such as: First, new tasks including compliance with terapeutic regimens seeking information about their diseases and managing their disconforts. Second, --losses referring to their social relationship, finances, locomotion and work capacity, and leisure activities losses. Third, treats --including treat to their personal self, their life and hope. PMID- 2099504 TI - [The preoccupations manifested by nursing students in relation to the discipline of nursing and transmissible diseases]. AB - Reactions like flight, anxiety, aggressiveness, and aversion are usually observed among students of nursing when they attend transmissible Disease subject, in Nursing Course. This symptoms are caused by the chance of contagion. The objectives of this study are to identify the students preoccupation of being infected or being a transmission vehicle of any transmissible disease, to their family or community and to verify what kind of diseases they are fear of being infected. PMID- 2099505 TI - [The meaning of perinatal death--the statements of mothers]. AB - The author's propose is to reveal the meaning of the perinatal death seen by mothers. For that, they used a qualitative methodology which makes possible a comprehensive analysis of mother's statements who are passing by this situation in the hospitals. The convergences of these speeches are analysed and they make possible the identification in some significative units that may establish and aid to guide the assistencial plan for mothers in order to observe their situation. PMID- 2099506 TI - [Evaluation: a theoretical-practical approach]. AB - The study presents a theoretical review and analysis of the evaluation of the teaching-learning process, as it occurs in the work of 2 nd. and 3rd. degrees teachers. A bibliographical review of the tendencies Evaluation and Mastery, Evaluation and is Prognosis, Evaluation and Transfer is made. The theoretical lines are afterwards compared with the speeches of the teachers interviewed with this purpose. The authors conclude that the three studied tendencies were found in the interviews, but no one was exclusive. PMID- 2099507 TI - [The student nurse confronting the question of human sexuality in the aspects referring to contraception]. AB - The authors criticize and make consideration on their own studies conducted in 1985, referring to the method used and the role of formal education in the transmission of the dominant ideology about human reproduction. PMID- 2099508 TI - [Nursing care for the mother-child dyad--the attitude of undergraduate nursing students]. AB - This study was carried out to verify the undergraduate students opinion about their experiences in nursing assistance to new born baby and the postpartum woman in separated and integrated ways. The factors investigated were opportunity for education, interation, teaching value in the fifth semester and its contribution to the community. PMID- 2099509 TI - [The basic ideas about the use of the Swan-Ganz catheter]. AB - The haemodinamic monitorization through the Swan-Ganz catheter is a valuable source in the assistance of the critically ill patient. This work is a review on the importance, indication, skills and nursing care in order to use this source. PMID- 2099510 TI - [Heart failure with normal systolic function (realities and uncertainties)]. PMID- 2099511 TI - [Thrombolysis and transluminal coronary angioplasty in acute myocardial infarction. Report of the Ischemic Cardiopathy Section of the Spanish Society of Cardiology]. PMID- 2099512 TI - [Factors affecting early graft patency after coronary grafts]. AB - From June 1984 to December 1987, an early postoperative angiographic study was performed in 247 patients who underwent isolated coronary artery bypass surgery. The average age of these patients was 58.6 years, range 31 to 75 years. Preoperatively 50.8% of patients had myocardial infarction and 43.2% of them had unstable angina before surgery. Early coronary artery bypass angiogram was performed in 683 grafts (2.76 grafts per patient): 74 internal mammary artery grafts and 609 saphenous vein grafts. The distribution, location and type of the stenosis, distal coronary artery diameter, segmental myocardial contractility, and distal angiographic coronary filling are analyzed with a matching statistical method. Multivariate analysis showed significant predictors of early graft occlusion to be right coronary and circumflex artery, poor or non visible distal angiographic filling, coronary arteries smaller than 1.5 mm. The univariate analysis associates as risk factors hypokinetic or akinetic territories and multiple stenosis coronary arteries. It can be concluded that the early angiographic study demonstrate that coronary arteries with multiple stenosis, poor distal angiographic filling, smaller than 1.5 mm in diameter, coronary arteries perfusing hypokinetic or akinetic territories and the right coronary and left circumflex artery grafts have significantly lower early cumulative patency rates. PMID- 2099514 TI - [Transesophageal Doppler color echocardiography in the evaluation of patients after percutaneous mitral valvuloplasty]. AB - To determine the value of transesophageal ultrasound in the assessment of patients after percutaneous mitral valvuloplasty, 42 patients were studied by transthoracic (TTE) and transesophageal (TEE) two-dimensional and color Doppler echocardiography. All of them were studied as out-patients and without complications. We describe the technique, planes of examination and the advantages that this new acoustic window offers in patients after balloon valvuloplasty regarding to: detection of thrombus in the left atrium (LA), visualization of spontaneous echo contrast in the LA, evaluation of mitral regurgitation (MR), detection of small atrial septal defects (ASD) and evaluation of the stage of the commissures of the mitral valve. We detected thrombus by TEE, in 5/42 vs 1/42 by TTE approach. Spontaneous echo contrast was found in 35/42 by TEE and none by TTE. Small ASDs were visualized in 10/42 patients vs 2/42 by TTE. No differences were found in the evaluation of MR and mitral valve commissures either by TEE or TTE. We conclude that transesophageal echocardiography is a well tolerated technique in outpatients which complements and improves the information obtained by the transthoracic approach in patients after balloon mitral valvuloplasty. PMID- 2099513 TI - [Coronary angioplasty: experience at the University Hospital of Madrid]. AB - The results of 963 consecutive coronary angioplasties, with 1.135 lesions attempted in 816 patients, were prospectively analyzed. Initial angiographic success (residual stenosis less than 50%) was achieved in 1.017 lesions (89.6%), and final success was obtained in 838/963 procedures (87%). Major complications included: emergency surgery in 4 cases (0.4%), acute myocardial infarction in 28 (2.9%), and death during hospitalization in nine (0.9%). Surgical stand-by was required only for cases with vital risk should the attempted vessel occlude. This criteria was present in 230 (23.8%) angioplasties. Coronary angioplasty was performed during the diagnostic procedure in 300 (31.1%) case, with final success in 264 (88%) of them. A exercise test was achieved before the procedure in 419 (50%) successful angioplasties and in 246 (58.7%) of them it was abnormal because of angina (with or without ST depression). After procedure, exercise could be performed in 780 cases (93%), and the result remained unchanged in only 44 (5.6%) (p less than 0.01). At discharge 780 (93%) patients with final success considered themselves clinically improved. In our experience, coronary angioplasty is a good myocardial revascularization technique, with high success, low rate of major complications, and that provides a good clinical outcome. Surgical stand-by may be unnecessary in prost of angioplasty procedures if patients selection is carefully done, also, this approach makes it possible to perform angioplasty at time of diagnostic catheterization. PMID- 2099515 TI - [Functional capacity and rhythm changes after atrial correction of transposition of great arteries]. AB - A group of 12 patients, previously submitted to atrial correction of the transposition of the great vessels, were studied through stress test with direct metabolimetry and Holter to assess aerobic functional capacity and its relationship with conduction disturbances. The results were compared with those obtained with a control group of 23 non athletic healthy children. All the patients showed amputation of their heart rates on effort, though this parameter and the oxygen consumption were normal at low work load levels. The VO2 at anaerobic threshold, the maximum VO2, and the maximum work load were also decreased in most of the patients. Holter studies demonstrated sick sinus syndrome in nine of them. Aerobic functional capacity was reduced in most of the patients with atrial correction of the transposition of the great vessels. The amputation of the heart rate on effort is a common finding though its relationship with the decrease of the aerobic functional capacity in these patients is limited. Finally, the stress test is probably more sensible than Holter for the detection of slight degrees of sinus disfunction. PMID- 2099516 TI - [Anisotropy and reentrant ventricular tachycardia: experimental model in the isolated rabbit heart]. AB - The purpose of this study was to study the role of anisotropic distribution of conduction velocity in the initiation and perpetuation of ventricular tachycardia in an experimental model of sustained reentrant ventricular tachycardia in the Langendorff perfused rabbit heart. The hearts of 30 rabbits were used in the study. The right ventricle, the interventricular septum and the endocardial and intramural layers of the left ventricle were destroyed by freezing. In the surviving epicardial layer an obstacle was created using a cryoprobe. Thus, the final preparation consisted of a perfused ring of epicardium in the left ventricle. In 27 of 30 experiments programmed electrical stimulation induced sustained reentrant excitation around the obstacle. The cycle length of the tachycardia ranged from 128 to 197 ms in different experiments (mean 162 +/- 17 ms). During tachycardia in some segments of the ring the impulse propagated parallel to fiber orientation at a mean conduction velocity of 61 +/- 7 cm/s whereas in other segments of the ring the impulse propagated perpendicular to fiber orientation at a mean conduction velocity of 22 +/- 4 cm/s. An excitable gap was present during all episodes of tachycardia. In conclusion, conduction velocity during reentrant tachycardia depends on the relation between direction of propagation and fiber orientation. This anisotropic distribution of conduction velocity can play an important role in the initiation and perpetuation of ventricular tachycardia. PMID- 2099517 TI - [Heart valve diseases. XI. Prosthetic valve dysfunction]. PMID- 2099519 TI - [Anomalous origin of the left coronary artery from the pulmonary artery: diagnosis by two-dimensional Doppler color]. AB - A case of anomalous origin of the left coronary artery from the pulmonary artery (ALCA) is presented. The noninvasive diagnosis was made by 2D-color flow Doppler. Application of this technique may alleviate the necessity for angiography in patients with ALCA. PMID- 2099518 TI - [Spontaneous echocardiographic contrast in the left ventricle related to aortic insufficiency]. AB - A case of spontaneous echocardiographic contrast in the left ventricle of a patient with severe aortic insufficiency is presented. This contrast appeared through the mitral valve which opened mainly during tele-diastole. Pulsed Doppler showed the blood flow responsible was laminar and of normal velocity. The mechanism of spontaneous intraventricular contrast cannot be attributed to poor left ventricle function or to high-velocity turbulent flow. We believe that spontaneous contrast was triggered by the decrease in proto-diastolic mitral flow secondary to aortic insufficiency. Transient stagnation of blood in the left atrium might modify the echogenic characteristics of the blood which persist during the passage of the flow through the left ventricle. PMID- 2099520 TI - [Repeated cerebral embolism in a patient with papillary fibroelastoma of the mitral valve detected by two-dimensional echocardiography]. AB - We report a 68 years-old woman with repeated cerebral embolism, secondary to a papillary fibroelastoma of mitral valve, located in its ventricular side. It was detected by two-dimensional echocardiography. Surgical treatment was satisfactory. PMID- 2099521 TI - [Signal averaging high resolution electrocardiogram. Ventricular late potentials]. PMID- 2099522 TI - [Electrical cardioversion after quinidine administration]. AB - The aim of the present study was to investigate the influence of quinidine on the effectiveness of electrical cardioversion (CV) for the reversion of supraventricular arrhythmias, the amount of electrical energy necessary for the CV and the possible complications of electrical CV. Initially, 100 CV procedures were allocated to the control group (patients free from the action of any antiarrhythmic drug), and 50 CV to the quinidine group. Quinidine was given as dihydroquinidine C1H at a dose of 500 mg/12 hours since the day before CV. In the last group, 6 (12%) patients reverted to normal sinus rhythm before electrical CV. At the time of electrical CV (100 procedures in the control group and 44 in the quinidine group), the patients who received quinidine required a lower amount of electrical energy, and showed a lower incidence of atrial premature beats as compared with the control group (11.3% versus 28%, p less than 0.05). A similar proportion of patients reverted to sinus rhythm in both groups. We conclude that the administration of quinidine before electrical CV has the following advantages: 1) 12% of patients reverted to normal sinus rhythm before electrical CV; 2) quinidine reduced the amount of electrical energy necessary for the CV, and 3) quinidine reduced the incidence of atrial premature beats after electrical CV. On the other hand, quinidine had no influence on the incidence of ventricular arrhythmias after electrical CV. PMID- 2099523 TI - [Long-term experience with multivalve replacement with the Medtronic-Hall mechanical prosthesis]. AB - During the period from January to September 1986, 182 Medtronic-Hall (M-H) heart valve prostheses were implanted in 89 patients, mainly because of rheumatic valve disease (68.5%). The patients were divided in two groups. Group I consisted of 83 patients with aortic and mitral valve replacement. Six patients with tricuspid valve replacement plus aortic and/or mitral valve replacement constituted group II. In group I the majority of the patients (86.7%) were in functional class III or IV (NYHA). Twenty three patients had undergone at least one previous cardiac operation. Hospital mortality was 6.02% (5/83). In group II the patients were in functional class III or IV (NYHA). Hospital mortality was 33.3% (2/6). Death occurred in the operating room in only one instance. Follow-up was completed in 98.9% and extended from 27 months to 8 years (348.7 patient years in group I and 23.08 patient years in group II). The overall 5 and 8 years actuarial survival, freedom of thromboembolism and freedom from endocarditis rates in group I were: 80.8 +/- 4.4% and 72.7 +/- 5.2%; 89.8 +/- 4% and 85.8 +/- 4.7%; 94.8 +/- 1.2 and 93.1 +/- 1.7%. In group II, actuarial studies were not carried out because of the scanty number of cases. There were another complications in group I: haemorrhage due to anticoagulation in 6 cases, hemolysis in 8 instances and periprosthetic leaks in 2 cases. There were no cases of structural failure. We conclude that after 8 years of follow-up the M-H valve prosthesis shows an excellent clinical performance and mechanical reliability, and the incidence of valve-related complications was in the low range of that reported with other mechanical prostheses. PMID- 2099524 TI - [Pulmonary valvuloplasty in adolescents and adults: 2 year follow-up by continuous Doppler]. AB - The purpose of this study is the long term follow-up of the first pulmonary valvuloplasties performed by our group. From september 1984 to march 1988, 10 patients (4 men and 6 women) aged 8 to 58 (mean: 21) with severe or moderate pulmonary valve stenosis underwent pulmonary valvotomy. In all cases the balloon diameter was equal to or 1 mm smaller than the valvular annulus. The results were satisfactory with a significant mean gradient reduction of 51.7%. A follow-up gradient estimation by Doppler echocardiogram was obtained 10 to 37 months after valvuloplasty (mean: 23 months). The mean follow-up gradient by Doppler (31.3 +/- 9.9 mmHg) was not significantly different from the mean hemodynamic post dilatation gradient (35.6 +/- 14.7 mmHg). A linear correlation was found between the post-dilatation hemodynamic mean gradient and the mean gradient by Doppler follow-up (r = 0.66, p less than 0.05, SEE = 4.1 mmHg). No restenosis were observed. These results suggest that the benefits of valvuloplasty are long lasting. Continuous Doppler is an excellent technique for the follow-up of these patients. PMID- 2099525 TI - [50 hz alternating current as a cause of inhibition of monopolar ventricular pacemakers]. AB - It is not well established the importance of 50 Hz alternating current (AC) (that supplies most of house appliances) as a source of inappropriate inhibition of today cardiac pacemakers (PM). This problem has been studied in 58 consecutive patients permanently paced (VVI unipolar) for AV block with 27 different PM models from 11 manufacturers. Under ECG monitoring, 50 Hz AC was applied through a pair of electrodes set at both patient's wrists using a battery powered external source, with voltage ranging between 0 and 45 V. Inappropriate inhibition was considered if PM pauses longer than twice the programmed escape interval of the PM were observed during interference. This happened in 46 patients (79.3%), with PM from all 11 manufacturers, with voltages ranging from 3 to 28 V. In each case, inhibition was seen with a narrow voltage window between no interference detection and interference reversion of the PM. Only 3 patients (5.2%) referred perception of electrical current during the study. Three of the patients studied had complained, prior to the study, about dizziness or presyncope related to touching electrical devices and in all of them inappropriate inhibition was observed during interference. We conclude that: 1) it is possible to demonstrate inappropriate inhibition caused by 50 Hz AC galvanic interference in a high percentage of unipolar PM; 2) This inhibition occurs at current levels that in most cases are not sensed by the cutaneous nerves, and 3) although the problem seems to have little clinical significance it should be investigated in paced patients with symptoms attributable to inappropriate inhibition of their PM. PMID- 2099526 TI - [Experimental evaluation of the role of the coronary sinus pressure in the regulation of coronary return volume via the coronary sinus. Surgical considerations in atrio-pulmonary diversion procedures]. AB - In order to find out the validity of the vascular waterfall mechanism in coronary venous circulation, the role of coronary sinus pressure in the regulation of coronary return volume via the coronary sinus is studied in healthy animals. An experimental model of pressure regulation in the coronary sinus was prepared, and aortic pressure, EKG and the cardiac output (measured by thermodilution) were recorded. The return volume via the coronary sinus was measured at coronary sinus pressure of 10 or less, 15, 20, and 25 mmHg or more, for a total of 36 determinations. Increased coronary sinus pressure did not produce significant changes in aortic pressure, heart rate, cardiac index or coronary return volume via coronary sinus. When coronary sinus pressure was 25 mmHg or more, there was a significant decline in the average of coronary return volume via coronary sinus. Nevertheless, stepwise variant regression showed that the coronary sinus pressure per se does not condition the volume of coronary return via the coronary sinus. Our results suggest that in the healthy animals, the vascular waterfall mechanism in coronary venous circulation is not valid. Our results suggest that in the correction of congenital cardiac malformations using atriopulmonary anastomosis procedures, employing techniques that ensure coronary sinus drainage into the left atrium, in order to avoid the hemodynamic repercussions attributable to the vascular waterfall mechanism, is not justified. PMID- 2099527 TI - [Role of percutaneous valvuloplasty in rheumatic mitral valve stenosis. Cordoba Las Palmas cooperative study]. AB - This article describes our findings on a prospective and cooperative study (Cordoba-Las Palmas) in 203 patients with mitral stenosis who underwent balloon valvuloplasty using a retrograde transarterial technique. We analyzed the immediate and mid-term results, and studied the factors determining an optimal result and those related to the new appearance or worsening of mitral incompetence after the procedure. On the other hand, we analyzed the results of mitral valvuloplasty in patients with previous mitral surgery, mild mitral stenosis and patients dilated while having an acute pulmonary edema. We observed a marked decrease in mean mitral gradient (17 +/- 7 to 6 +/- 3 mmHg; p less than 0.001) as well as a significant increase in mitral valve area (1.02 +/- 0.4 to 2.04 +/- 0.7 cm2; p less than 0.001). Echo-Doppler follow-up did not show significant changes in the residual mitral valve gradient. Multivariate analysis selected, as independent predictors of an optimal result, the presence of a pliable valve and the absence of basal mitral regurgitation. On the other hand, the presence of a lower ejection fraction, an older age and a higher baseline left ventricular endiastolic volume were independent factors determining progression of mitral regurgitation. In patients with previous mitral surgery, the clinical, echo and hemodynamic profiles, as well as the immediate results, were similar to those observed in patients with unoperated mitral stenosis. In the subgroup of mild mitral stenosis, we observed and optimal result in all cases, without major complications. Mitral valvuloplasty was dramatically effective in 8 patients treated during acute pulmonary edema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099528 TI - [Post-traumatic annular subvalvular aortic aneurysm. Report of a case]. PMID- 2099529 TI - Calcium-activated, phospholipid-dependent protein kinase activity in calf platelets. AB - Protein kinase C (PKC) has been widely studied from different tissues of mammals. Human platelets display higher levels of PKC activity, if compared with other sources. The PKC activity from calf platelets crude extract was determined in the presence of various protease inhibitors such as PMSF, Leupeptin or Trypsin inhibitro, and the Ca(2+)-chelators EGTA and EDTA. The free calcium requirement was 0.25 mM, calculated with the help of the Solgas-water computer program, which represents 1 mM CaCl2, in these assay conditions. Optimum PKC activity was obtained at 4 min in the presence of PS plus DAG or TPA, using H1 type III-S histone as substrate. Phospholipid-interacting drugs, such as trifluoperazine, chlorpromazine and tetracaine, inhibited the PKC activity in a dose-dependent manner. Triton X-100, a non-ionic detergent, which is usually employed to solubilize the membrane fraction, in different translocation assays, inhibited PKC activity at concentrations higher than 0.01%. In these conditions, non proteolytic PKC activity from calf platelets was easily determined, and shares similar activity levels with those described in human platelets. PMID- 2099530 TI - RNP, Sm and SS-B antigens from calf thymus: molecular stability upon enzymatic digestion. AB - RNP, Sm and SS-B nuclear antigens from calf thymus were studied with respect to the size distribution on sucrose gradients as well as to the molecular integrity and related structural changes when they were subjected to enzymatic digestions under different conditions. Making a difference with RNP particles, the Sm size distribution is concentration dependent, a property in accordance with the complexity of the Sm particles in comparison with the RNPs. The use of combined effects of temperature, endogenous proteases and RNase A, allowed us to gain insight into the limits of stability of the three antigenic particles. Following treatments in the absence of RNAse A, the degradation products (32-38 Kd molecular weight) of the 70 Kd RNP polypeptide remain stable and associated with other molecules within the RNP particle. It was also found that the phosphate groups of the SS-B protein moiety are only accessible to alkaline phosphatase if the RNA of the SS-B particle is degraded by the action of RNAse A. PMID- 2099532 TI - [Visual evoked potentials produced by monocular flash stimuli in the cerebral cortex of the rabbit. I. Typology]. AB - Visually evoked potentials obtained from the cerebral cortex of pigmented rabbits in response to monocularly applied flashes were studied. In agreement with their morphology, the VEP of the cerebral cortex of the rabbit were classified in three fundamental types: the first one is characterized by the presence of a large positive wave, (P1), followed by a negative wave, (N1), and finally, another positive wave, (P2); these last two being of quite variable amplitudes. The second one is characterized by an initial large negative wave, (N1), followed by a usually large positive wave, (P2). Should a positive, (P1), appear previous to N1 there would be little amplitude. The third one is characterized by the presentation of an early negative wave, (N0), of variable amplitude. This is usually followed by a large wave, (P1). N1 and P2 are present but their amplitude is variable. PMID- 2099531 TI - Specific IgG and IgE responses to Dermatophagoides pteronyssinus in Sprague Dawley rats. AB - Specific IgG and IgE antibodies against the mite Dermatophagoides pteronyssinus (Dp) have been determined in the serum of Sprague Dawley (SD) rats by enzyme linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA), respectively. Immunization of rats with Dp produces a rapid increase of serum specific IgE antibody levels which decrease when specific IgG antibodies start rising. The results indicate that the SD rat is a good model to induce a humoral immune response to allergen Dp. PMID- 2099533 TI - [Visual evoked potentials produced by monocular flash stimuli in the cerebral cortex of the rabbit. I. Typography]. AB - The visually evoked potentials in the hemisphere contralateral to the stimulated eye in rabbit, can be described topographically as follows. While a positive wave (P1) begins forming in the anterior zones and in the V I binocular zone, the N0 wave, at times very large, is produced in a more occipital zone, which corresponds to the visual streak. Immediately afterwards, the positivity, P1, practically invades the whole of the hemisphere. After this, the N1 wave which is produced in the most posterior parts of the V I, begins forming. The whole phenomenon comes to an end when the P2 wave is generated in the most occipital zones. PMID- 2099534 TI - Cell wall acyl-lipids, proteins and polysaccharides in mature and germinated olive pollen. AB - Proteins, acyl-lipids and polysaccharides from cell walls of mature and germinated olive pollen were studied. In general, hemicelluloses are the most abundant polysaccharides, arabinose in mature and glucose in germinated pollen being the main components of these macromolecules. Protein content and its amino acid composition are very similar in walls from mature and germinated pollen, these compounds showing a weak acid character. Free-fatty acids are the most abundant lipid molecules in mature and germinated pollen walls and a decrease in acyl-lipids, especially in polar lipids, as well as a higher unsaturation of their fatty acid components are observed after germination. PMID- 2099535 TI - [Biological profile of tartrate-resistant acid phosphatase as a marker of bone resorption]. AB - Tartrate-resistant serum acid phosphatase was measured in 123 subjects, 80 of which were normal and the rest pathologic, in order to define the profile and value of this parameter as a biological marker of osteoclastic activity. Normal subjects were divided into age groups based on the period where skeletal growth ends (under 20 years), at the age of menopause in women (50 years, between 20 and 50 years) and those over 50 years. There was an increase in tartrate-resistant serum acid phosphatase coinciding with puberty and no sex differences were observed after the 50 year mark, when women showed higher values than men (p less than 0.001). Such tartrate-resistant serum acid phosphatase increase, is reflected as higher values in the 50 year group than in the 20 to 50 year group (p less than 0.001), the only age limit where a negative significant correlation between tartrate-resistant serum acid phosphatase values and age could be observed (p less than 0.05). Values were higher up to the age of 20 years (p less than 0.001) than in any other older age group. Levels increased significantly (p less than 0.001 for both groups) in post-menopausal osteoporosis (n = 20) and in Paget's disease of bone (n = 15), and decreased significantly (p less than 0.05) in imperfect osteogenesis (n = 8), thus revealing its value as a biological marker of osteoclastic activity. PMID- 2099536 TI - [Developement and quality control of a radioimmunoassay for measurement of endogenous digoxin]. AB - It has been suggested that sodium renal excretion is regulated, at least partially, by a factor with natriuretic properties called digoxin-like factor (DLF). As this substance crossreacts with digoxin antibodies, it was measured with a radioimmunoassay used to determine exogenous digoxin. Methodological conditions and quality control to determine DLF in plasma and urine have been established. Good correlation coefficients in specificity as well as dilution studies were obtained. Within--and between--assay coefficients of variations indicate good reproducibility. Moreover, changes in plasma DLF levels were detected in patients with cirrhosis or with renal failure, diseases which thrive on alterations in salt and water metabolism. In conclusion, this radioimmunoassay method for measuring DLF may be useful to investigate the role of this factor in several physiological and pathological conditions. PMID- 2099538 TI - [Biomechanics of orthodontic movement--initial response of periodontal tissue]. AB - There occurs a biological response of the tissues of dental support, in answer to the external physiological forces and those realized during clinical treatments with orthodontical purposes. These forces differ from the first ones because they are continuous and time dependent. A great dental mobility is related to the degree of tissue organization of the periodontium system and the orthodontical movement must utilize this exceptional capacity of renewal and adaptation of the periodontium structures adequately. Therefore, through histological means a search was made to evaluate the succession of alterations of the periodontium system after the application of an orthodontical force on the molars of young rats and to interpret the standards of horizontal mobility and their consequences on the periodontium structures, biologically. An orthodontic force was applied on young rats utilizing steel wire placed in a ring form on a contact point between the first and second lower molars. The animals were sacrificed after 30 minutes, 1, 2, 6, 12, 24, 48, 72, 96 and 168 hours after the placement of the metal ring. After technical preparation, the microscopic slides were examined and the results were compared. In all the sections there was evidence of an intense metabolic activity. A gradual evolution of modification on the phenomenons had occurred. PMID- 2099537 TI - Soluble and membrane-bound leucyl- and arginyl-aminopeptidase activities in subcellular fractions of young and adult rat brains. AB - The subcellular distribution of soluble and membrane-bound leucyl- and arginyl aminopeptidase activities were analyzed in one and five month old rat brains using Leu- and Arg-2-naphthylamide as substrates. Both soluble leucyl- and arginyl-aminopeptidase activities showed the highest levels in the synaptosomal fraction in the two groups of rats. The highest levels of membrane-bound leucyl- and arginyl-aminopeptidase activities were found in the microsomal fraction in the two ages studied. There were no differences between the two ages in soluble leucyl- and arginyl-aminopeptidase activities. However, a significant decrease in both membrane-bound enzymatic activities was evidenced in the synaptosomal fraction of older rats. Developmental changes of these aminopeptidase activities in a determined subcellular localization, may reflect modifications in their effect on neuropeptides susceptible to be hydrolyzed in this particular location. PMID- 2099539 TI - [Presence of debris in the apical region of dog teeth after biomechanical preparation with or without the use of an auxiliary cream substance]. AB - The subject of this work is to observe if the employment of a cream (ENDO-PTC) during the root canal preparation contributes or not to the condensation of debris in the apical region. Twenty root canals of dogs teeth were divided into two experimental groups: in the first one, the biomechanical preparation was carried out up to the n. 50 Kerr file by using irrigation and aspiration with sodium hypochlorite. In the second experimental group the canal negotiation was done in the same way but using a cream (ENDO-PTC) with sodium hypochlorite as a lubrication substance. A final irrigation and aspiration with sodium hypochlorite was also done in this group. The animal was killed and the pieces prepared for histological analysis. The histological results show us that the employment of a cream during the negotiation of the root canal contributes to a higher condensation of debris in the apical area. PMID- 2099540 TI - [Hardening treatment for gutta-percha cones]. AB - The subject of this work was to study a hardening procedure for gutta-percha points, in order to make ease their introduction in very curved root canals. Gutta-percha points of different brands and dimensions were submitted to treatment with alcohol 96 degrees for 1 to 3 days. After this treatment the weight necessary to make a bending of 35 degrees on the tip of the gutta-percha was evaluated. The obtained results were submitted to statistic analysis and the following conclusions can be observed: a. The treatment with alcohol make hard the gutta-percha points in a significant level. b. There was not significant differences between the results obtained with more than one day of alcohol treatment. c. The treatment with alcohol do not make hard all the brands of gutta percha points. PMID- 2099541 TI - [Direct immunofluorescence in the study of palatal mucosal changes compatible with chronic atrophic candidiasis in mucosal supported complete denture wearers]. AB - Histopathology by hematoxilin-eosin (HE) and periodic acid Schiff (PAS), concomitant direct immunofluorescence (DI) against total human immunoglobulins and against Candida albicans, was effectuated in 25 persons dentures wearers. In 5 persons without chronic athrofic candidiasis (CAC) clinical signals in the palate the HE showed wise inflammatory elements in the connective tissue and the PAS marked the continuous basal layer, the intra-cellular grains of granular layer and the uniform parakeratin on epithelial surface. In 20 others, with palatal signals of CAC, in the HE was frequent the features encountered in Candida infected and PAS revealed, beside descontinuous lamina basal and epithelial surface covered by tide and discontinuous parakeratin, the presence of round bodies few largers that presents in the granular layer, casually isolated in the medial portion of ret pegs and connective papillae. In the first 5 persons the DI against total human immunoglobulins not showed signals of the humoral immunologic phenomena, the same was valid to others 20 patients with CAC clinical aspects. However the DI with conjugate against C. albicans in the 20 cases with CAC signals revealed suitable aspects of the structures assumed by Candida in tissues. Cultures of samples obtained of the persons with CAC signals was positive in 100% to Candida, 70% presumptively albicans, against 80% of positiviness to generus Candida, 67% presumptively albicans, in the persons without CAC signals. PMID- 2099542 TI - [Transposition of masseter muscle insertion and its influence on anatomical musculo-skeletal changes in the adult rabbit]. AB - Unilateral surgical transposition of the masseter muscle from the masseteric fossa to the central area of the mandibular body below the molar teeth was performed in ten adult rabbits. Six months later the animals were sacrificed, the masseter muscles were dissected and then removed to be fully dried and weighed; the skull was cleaned for anatomical examination of the mandible and the teeth. It was noticed that the transposed muscles were firmly attached and functionally adapted, but underwent a drastic reduction of their weight. The smooth surface of the mandibular body which became activated by the new muscular pull was now rough and irregular due to osseous neoformation. The original area of attachment (masseteric fossa) was remodelled not only regressively but also by bone apposition (exostoses) in some sites. The dental arches kept normal, except for alveolar bone resorption next to the first molar in two animals and accentuated sagittal deviation in another one. PMID- 2099543 TI - [Change in body weight and mandibular development in rats from fluoride administration]. AB - The body weights evolution and the development of mandible were analyzed in rats that received 0.25 mg F contained into a commercial product, during 30 and 60 days consecutively, beginning at birth. The study presented the following conclusions: 1. The treated animals showed body weights always inferior to the controls, with more evident difference at 60 days period; 2. Analysis showed a reduction in the horizontal linear measurements, but not in the length of the mandibular diastem. No influence was observed in relation to the verticals. PMID- 2099544 TI - [Fluoride concentration and enamel solubility of deciduous and young permanent teeth after application of topical fluoride solutions]. AB - The aim of this article was to compare, through the distillation method, the incorporated amount of fluoride and the reduction of solubility in the enamel of both deciduous and young permanent teeth, following topical application of a 2% neutral sodium fluoride solution, according to the Knutson's technique and a 1.23% of acidulated solution, according to the Wellock & Brudevold's technique. The greatest fluoride incorporation was observed in the deciduous teeth after the usage of the 2% neutral solution. The amount of calcium and phosphorus liberation by the acid solution was greatest in the control group, followed by the group of teeth treated in acidulated solution and, finally, by those treated in 2% sodium fluoride solution. PMID- 2099545 TI - [Penetration of calcium hydroxide based cements by dental enamel conditioning acids]. AB - It was verified the penetration of phosphoric acid into 3 commercial calcium hydroxide-based cements (Life, Renew and Prisma VLC Dycal). The colorimetric method employed permitted the identidication of phosphorus amount in representative samples of 6 successive layers 0.1 mm thick of each material. The acid etching used were the commercial products Scotchbond Etching Gel--3M at 36.114% by weight and Solucao Condicionadora--Johnson & Johnson at 36.054% by weight. The contact time was 60 seconds. The result showed that layers 0.1 mm tick for Life and Prisma VLC Dycal and 0.2 mm thick for Renew were able to block the penetration of phosphoric acid solution whereas layers 0.1 mm thick for the 3 cements were able to block the penetration of phosphoric acid gel. PMID- 2099546 TI - [Influence of different bonding agents on traction resistance of metal alloys to dentin]. AB - They were casted pieces using three kinds of alloy (Ni-Cr, Ag-Sn and Cu-Al) with circular and smooth surface. They were cemented to human teeth, on occlusal surface, grounded at dentin level, through three different materials kind (zinc polycarboxylate cement, glassionomer cement and composite). After 24 hours storing, the samples were subjected to the tensile test. The results showed that the samples cemented with composite and the casts made with Ag-Sn alloy had higher bond strength. PMID- 2099547 TI - [Marginal leakage in composite resin restorations in posterior teeth. Effect of material, cavity preparation and enamel conditioning at the cervical level]. AB - The purpose of this "in vitro" study was to investigate the cervical marginal leakage in class II restorations with chemically cured resin (P10) and light cured resin (P30) in two types of cavities: conventional and adhesive. The effect of acid-etching in this area was also observed. Dentine adhesive Scotchbond was used in all experimental groups. Leakage was evidenced by Rodamina B dye penetration after thermocycling procedure between 10 degrees C and 50 degrees C temperature and analysed by using Zeiss Stereoscopic Magnifying Glass (10 X). According to the results obtained marginal leakage occurred in all experimental groups, with lower percentage for adhesives cavities when enamel acid-etching and light-cured resin P30 was used. PMID- 2099548 TI - [Surface roughness of high copper alloys as a function of heating above casting temperature]. AB - Being the surface roughness a fundamental property in the fit of the castings, it was determined the roughness of 5 high-copper casting alloys, according to the heating over their melting temperature. That way, the specimens made with smooth plastic in the shape of a rectangular plate, 2 mm x 7 mm x 11 mm were invested into a cristobalite investment. After heating and elimination on the plastic, the molds were filled by 3 g of molten alloy, casted in a electrical casting machine at the casting temperature at 25 degrees C and 50 degrees C overheating. The surface roughness was measured in a roughness analyser, Talysurf. As a result, it was verified that there is a variation of surface roughness among the alloys tested, and the heating of the alloys until 50 degrees C over the melting temperature does not interfere in the roughness. PMID- 2099549 TI - [Study of the cervical portion of the facial vein of fetuses, newborns and children]. AB - In the study of cervical posterior of the facial vein of the foetus, newborns and children we injected in the veins of the head and neck of 15 corpses, rubber material (Xantopren and or Neoprene Latex). The results showed than the retromandibular and or the facial vein form a venous trunk in 83.3%, what finish always in the intern jugular vein or join the retromandibular vein and casually also with a posterior auricular vein originating the extern jugular vein (16.7%). PMID- 2099550 TI - [Effect of casting techniques on castability of copper-aluminum alloys]. AB - It was evaluated the castability of four copper-aluminium alloy according the melting casting method used. The specimens were made using polyester mesh screen, with 11 x 11 filaments of 0.26 mm thick, fixed along of two adjacent edges in wax bar, with the sprue attached at their junction. The alloys were in an electrical casting machine and a centrifugal casting machine with an air/gas torch. The castability values were obtained by the percentage of completed segments of the resulting cast alloy screen. It was verified that the use of the electrical casting machine produced higher castability values to the copper-aluminium alloys than those produced by a centrifugal casting machine with an air/gas torch. PMID- 2099551 TI - [Determination of copper alloy hardness, in original form and after casting as a function of casting techniques]. AB - It was evaluated the Vickers hardness of five high-copper casting alloys, in their original package form and after casting, according to the casting method used. That way, ten ingots, supplied by the manufacturers of each alloy, were included in self-curing acrylic resin, polished, numerated and submitted to Vickers hardness test at load of 200 g during 30 seconds. Afterwards the numerated ingots were removed from the acrylic resin and five of those were cast in an electrical casting machine and the other five in a centrifugal casting machine with an air/gas torch. The specimens obtained were included in self curing acrylic resin, polished and submitted to Vickers hardness test. As a result it was verified that there is a variation of hardness among the alloys tested, and the use of the electrical casting machine produced lower hardness values than those produced when used the centrifugal casting machine with an air/gas torch. Also, there is a decrease of hardness of the cast alloys when they are tested in their original form and after casting. PMID- 2099552 TI - [Resins for esthetic veneering of fixed dentures. 3. Simultaneous analysis of dimensional change variables and weight change as a function of materials, storage condition and time]. AB - The authors analysed the simultaneous effects of the dimensional and weight alteration of resins utilized for esthetic facets submitted to warehousing conditions and periods of time. The resins showed different behaviour and a neat correlation between dimensional alteration and weight. The condition of immersion promoted dimensional alteration 50% lower and an alteration of weight three times higher. PMID- 2099553 TI - [Comparative study of tensile strength of enamel/resin/metal interface. Effect of bonding resins, retention mechanisms and metal alloys]. AB - The purpose of this study was to compare the enamel/resin/metal bond tensile strength by using human canines, in which castings were bonded. These castings were obtained by Co-Cr or Ni-Cr alloys and showed four types of mechanisms of retention: 50 micrograms aluminum oxide abrasive, electrochemical etch, acrylic beads metal mesh. The castings were bonded utilizing Comspan Opaque and Panavia Ex. The specimens were subjected to tensile forces after 24 hours in an Instron machine. The castings subjected to 50 micrograms aluminum oxide abrasive and bonded utilizing Panavia EX showed the biggest bond tensile strength. PMID- 2099554 TI - [Fatigue of retentive clasps of removable partial dentures. Effect of alloys, thickness and casting techniques. 1]. AB - The authors looked for the verification of the fatigue of retentive clasps utilized on the removable partial denture. According to this, it was idealized and built on assay machine, that through movements, simulate the insertion and removal of the clasp for a pattern tooth, manufactured on cobalt-chromium which has all the preparation normally utilized to the correct confection of this type of prosthesis. It was utilized three different commercial alloys based on cobalt chromium: L1-Biosil; L2-Steldent; L3-Duracron. It was utilized the T clasp of Roach, with was tested upon three different proportions among width and thickness: E1-1.7;E2-2.0 and E3-2.3 and was casted through two casting techniques: F1-oxygen-gas and F2-oxygen-acetylene. The clasps were tested on the machine, which allowed the reading of the number of insertion and removal cycles made until fatigue appeared. The obtained results were submitted to the statistic analysis and the authors concluded that: a) L3 (Duracrom) obtained the best results followed by L1 (Biosil) and finally L3 (Steldent); b) among the analyzed thickness, the best results were obtained by E3, followed by E2 and after this E1; c) form the casting techniques, F2 gave us the best results. PMID- 2099556 TI - [Guided and unguided hinge axis in the totally edentulous]. AB - This investigation presents a commentary about two researches locating the terminal hing axis (THA) in totally edentulous people determined through the guided and not guided methods with chin compression. The main conclusions were: the emergency points of the THA were located in the anterioinferior quadrant; the definition of the emergency points of the THA will occur next the vertical dimension of occlusion position; the THA were determined in precise sites without difficult; each method located one THA. PMID- 2099555 TI - [Fatigue of retentive clasps of removable partial dentures. Effect of alloys, thickness and casting techniques. 2]. AB - The authors tested the T clasp of Roach in three differents proportions among width and thickness: E1-1.7; E2-2.0 and E3-2.3, with a constant length of 15 mm. These clasps were casted with three cobalt-chromium alloys (L1-Biosil; L2 Steldent and L3-Duracrom), through two casting techniques (F1-oxygen-gas and F2 oxygen-acetylene). The fatigue of the clasps were verified by using and assay machine, that through movements, simulate the insertion and removal of the clasps for a pattern which were obtained from a premolar, prepared in a surveyor. This machine detect the fatigue of the clasps and count the number of cycles of insertion and removal realized. The obtained results of the interaction between the analysed factors, were submitted to the statistic analysis and the authors concluded that: a) the interaction of factors, Alloy x Thickness, Alloy x Casting Technique and Thickness x Casting Technique did not change the order of effects that the factors showed separately but gave rise to effects of different magnitude for any observed sense; b) the simultaneous interaction of the factors Alloy x Thickness x Casting Technique confirmed the superiority of the L3 alloy, the thickness E3 and the F2 casting technique. PMID- 2099557 TI - [Prevalence of anodontia in 2nd level students in Sao Jose dos Campos-correlation between third molar anomalies and other teeth]. AB - The authors studied 201 school children form both sexes, aging 12 to 14 years, in order to identify anodontia, including in third molars. The results indicated a congenital absence of teeth in 24.37% of the examined children, distributed into 10.44% of boys and 13.93% of girls. Anodontia was observed concerning third molar teeth and other teeth, and the correlation was calculated by the total, sex, and hemiarch. The data were presented and discussed, and the results included several conclusions. PMID- 2099558 TI - [Frequency of fused roots, divergent separation, convergent separation, rectilinear separation and delaceration of third molars]. AB - In a sample of Brazilian white young adults between 18-23 years old, the A.A. studied the third molar roots, in anatomical aspects, using the orthopantomographic radiographic method. They concluded that the superior third molar shows a biggest number of fusionated roots (19.50% in the right side and 19.66% in the left side) and the inferior third molar shows a biggest number of separated roots (21.48% in the right side and 19.66% in the left side). PMID- 2099559 TI - [An oral health program for preschool children in Araraquara, SP-results during 1988]. AB - This paper reports the composition change of the dmf-teeth index, outcome from dental health program for the 3 to 6 year old pre-school children population, enrolled in kindergartens in Araraquara-SP, in 1988. The program performance promotes a major contribution of the "f" component to the dmf-teeth index. PMID- 2099560 TI - [Effects of ultrasonic stimulation on tooth extraction wound healing: histological study in rats]. AB - The effects of ultrasound on the wound healing process after teeth extractions were studied histologically. The right upper incisor was extracted in 56 rats. They were divided into 2 groups, one control (I) and one experimental (II). Group II received ultrasound stimulation that was applied with the frequency of repetition of 1,000 Hz and pulse length of 2,000 us continuously, during five minutes daily since the extraction day until 24 hours before the death. The rats were sacrificed at 3, 6, 9, 12, 15, 18, and 21 postoperative days. The results showed a precocious granulation tissue formation, faster remodeling of osseous ridges, and consequently acceleration of the alveolar wound healing process. PMID- 2099561 TI - [Radiographic study of the development of the permanent dentition of Brazilian children with a chronological age of 84 and 131 months]. AB - With the help of orthopantomograms we analyse the tooth development beside body weight and height from Brazilian healthy boys and girls. So, their dental age were compared to their chronological age. The results of this investigation, according to the methodology employed, indicated that: 1. girls showed accelerated formation of permanent teeth and mean values of dental age higher than boys; 2. the mean values of dental age in girls were higher than their chronological age in all groups; 3. the teeth development stages were appropriate in assessment of the degree of physiological maturity of a growing child. PMID- 2099562 TI - [Effect of cyclophosphamide on the development of incisor tooth germs in mice]. AB - Thirty six female mice were injected on the 12th day of the gestational period with 0.2 ml of distilled water (control group) or of an acqueous solution containing either 30 mg/Kg or 50 mg/Kg of body weight of cyclophosphamide (treated group). The animal were killed at 24, 48, 72, 96 and 120 hours after the injection and 3 days after birth. It was verified that cyclophosphamide interferes on the tooth germ development and that this effect is in directly ratio of the doses used. PMID- 2099563 TI - [Effect of cyclophosphamide on the development of tooth germs transplanted to the anterior eye chamber of mice]. AB - Mice foetus were killed between 13 and 16 days of the gestational period and their molar tooth germs grafted into the anterior chamber of the eye. The hosts were injected either with 6.25 mg/Kg or with 125 mg/Kg of cyclophosphamide and killed 15 days later. The cyclophosphamide irreversibly, interferes on tooth germ development causing either its total degeneration or an alteration on its morphology forming hypodeveloped tooth germs; its action is directly proportional to the foetus age and to the dose used; it does not induce the formation of osteodentin while some predentin partial cell inclusion may occur. PMID- 2099564 TI - [Comparative histological study of two methods of obtaining alveolar sections in rats]. AB - The chronology of the wound healing process following tooth extraction was studied by means of two kinds of histological cuts. Two groups of 42 albino rats were employed. In the first one, the sockets were cut in a transversal way. In the second one the cuts were performed in a longitudinal way. The rats were sacrificed after 3, 6, 9, 15, 21, 24, and 28 days following the surgeries. After laboratorial outline the obtained pieces were stained by hematoxylin and eosin for histological purposes. It way be concluded that: 1. The results got from longitudinal cuts were in agreement to those described by other authors; 2. The transversal cuts allow us to detect intensive resorption of the lateral alveolar wall at the cervical thirs; 3. On the 21st day following dental extraction the incisor socket of the rat shows a great deal of areas not ossified; 4. The healing process of dental extraction wounds of the upper incisor of the rat is completed between 24 and 28 post operative days. PMID- 2099565 TI - [Cutaneous healing after topical application of nebacetin and gingilone to infected wounds. Clinical and histological study in rats]. AB - It was performed a study to examine the cutaneous cicatrization of infected wound of skin after daily topic application of Nebacetin and Gingilone. Following clinical observations the animals were sacrificed after 4, 10 and 17 post operative days. The pieces were treated, analyzed, in an optical microscope. The topic application of Nebacetin showed to be more efficient in the epithelial reparation comparatively to the Gingilone and control group. PMID- 2099566 TI - [Comparative histological study of palatal mucosa in patients with and without complete dentures before and after insertion of new dentures]. AB - The authors verified histologically in 20 no dentates patients, the influence of complete dentures on the hard palate mucosa. The patients were divided in two groups: I. Patients that never used complete dentures; II. Patients that were using complete dentures when this research was realized. New prosthesis were made for each one of the 20 patients. Immediately before they received the new prosthesis and ninety days after this, biopsies were realized. The circunferencial pieces of the hard palate mucosa were fixed in formol 10% and coloured with Hematoxylin/Eosin and Mallory's Tricomic for histomorphologic analysis and measuring of the stratum corneum of the epithelium. It was made the statistical analysis and the results showed that: 1. In normal conditions, the utilization of the full dentures produces the reduce of the thickness of the stratum corneum. This was more observed in Group I. 2. The range difference of the thickness of the stratum corneum between the first and the second biopsies in the groups I and II (4.86 microns and 2.18 microns) were not statistically significant. 3. With the use of complete dentures the stratum corneum of the epithelium showed tendence to parakeratinization. PMID- 2099567 TI - [Behavior of periapical tissue of dog teeth after canal obturation with Sealapex with or without iodoform]. AB - Some endodontists use iodoform in Sealapex in order to rend it more radiopac. This procedure is empiric and for this reason we decided to observe, histologically, if the iodoform introduces some modification in the biological properties of Sealapex. Thirty root canals of dogs' teeth were overinstrumented and filled, by lateral condensation technique, with gutta percha points and Sealapex, with or without iodoform. The iodoform was added in two different proportions: 30 mg or 112 mg for one centimeter of the base and one centimeter of the catalyst of Sealapex. The pieces were removed for histological studies, 6 months after the treatment. The histological results showed that Sealapex encourages apical closure by cementum deposition and that the addition of iodoform does not change that biological property. PMID- 2099569 TI - Influence of nocturnal oxygen desaturation on circadian rhythm of testosterone secretion. AB - To investigate the influence of nocturnal oxygen desaturation on the circadian rhythm of testosterone secretion, polysomnography was performed on 2 consecutive nights in 24 male subjects who complained of loud snoring and/or obesity. During the first night, we collected blood samples every 4 h via a catheter and measured serum testosterone. We arbitrarily defined severe oxygen desaturation as that exceeding the baseline SaO2 by 4% during 80 min of total sleep time. The subjects were divided into 2 groups from the data of the second night; one was the severe desaturation group as mentioned above, and those who suffered less desaturation were classified as the free to mild oxygen desaturation group. We found that in the latter group peak testosterone levels appeared at 6 a.m. On the other hand, the severe desaturation group exhibited delayed peak testosterone levels, i.e. at 10 a.m. We calculated the ratio of the testosterone level at 10 a.m. to that at 6 a.m., and found a significant correlation between this ratio and total desaturation time (r = 0.446, p less than 0.05). These data suggest that severe oxygen desaturation may alter the circadian rhythm of testosterone secretion. PMID- 2099568 TI - Long-lasting effects on rheology and clearance of bronchial mucus after short term administration of high doses of carbocysteine-lysine to patients with chronic bronchitis. AB - The rheological behavior and clearance of bronchial mucus samples collected by protected expectoration from 24 out-patients with simple chronic bronchitis were investigated before, at the end of a short period of treatment (4 days) with a single oral dose of 2.7 g (sachet) of carbocysteine-lysine (evening meal), and on the 4th and 8th days after the end of treatment versus placebo. In the group treated with carbocysteine-lysine, there were significant reductions in viscosity (-67, -48, -62%) and increases in mucociliary transport (+41, +31, +34%) at the three times mentioned. The most striking finding was that the improvements were still present 8 days after cessation of treatment. The elasticity parameter was not affected in any statistically significant way (-10, -24, +65%). These findings suggest the presence of some type of 'post-mucoactive' effect. PMID- 2099570 TI - Cryptogenic fibrosing alveolitis. A study of an indigenous African population. AB - Cryptogenic fibrosing alveolitis (CFA) has not been described previously in any large group of indigenous African patients. This was a retrospective study of 46 such patients diagnosed as having CFA during a 73-month period. The clinical spectrum of illness was similar to that of other groups studied worldwide. Cigarette smoking was associated with a poorer outcome and is a potentially preventable cause of deterioration. PMID- 2099571 TI - PAF-dependent phosphatidylinositol turnover in platelets: differences between asthmatics and normal individuals. AB - The effects of nebulized platelet-activating factor (PAF) on the pulmonary and cardiovascular systems, and on the platelets present in peripheral blood were investigated in 9 normal individuals and in 6 patients with asthma and 3 individuals with lyso-PAF. The inhalation of PAF caused an acute decrease in specific airway conductance. The circulatory system parameters monitored showed an increase in heart rate while blood pressure decreased in both groups that were studied. The inhalation of PAF led to a significant increase in the differential count of polymorphonuclear leukocytes after 15 min; the count returned to the initial level after 24 h. However, the platelet count remained unchanged. The phosphatidylinositol (PI) turnover and in particular the formation of 1,4,5 inositoltrisphosphate (IP3) in platelets were investigated after PAF inhalation. It also mediated an increase in intracellular free calcium concentration, [Ca2+]i, in response to a second challenge with exogenous PAF. The basal levels of IP3 and [Ca2+]i were significantly greater in the platelets of patients with asthma than in those of normal individuals (p less than 0.01). Platelets that had been isolated from normal and asthmatic subjects had a higher concentration of IP3 and [Ca2+]i in the platelets after an in vitro exposure to PAF. After an inhalation challenge with PAF, the platelets of both the normal individuals and the patients with asthma showed a specific refractoriness to the in vitro exposure to PAF. Perhaps, this is an explanation for the PAF-dependent tachyphylaxis that is commonly observed in both normal and asthmatic individuals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099572 TI - Allergic sensitization in elderly patients with chronic obstructive pulmonary disease. AB - To study whether allergic sensitization occurs in elderly patients with chronic pulmonary obstructive disease (COPD), we examined serum IgE and skin test reactivity to allergens in three age-matched groups of normal subjects, and in patients with COPD and bronchial asthma (BA). Serum IgE was significantly higher in patients with COPD and BA than in normal subjects (p less than 0.05), and patients with COPD showed serum IgE levels as high as those of patients with BA. However, the skin test scores were significantly higher in patients with BA than in normal subjects and patients with COPD (p less than 0.05). Neither serum IgE nor skin test score significantly correlated with FEV1%, PaO2, PaCO2 or Brinkman's Index in any group (p greater than 0.20). These results suggest that allergic sensitization occurs in elderly patients with COPD and that symptoms associated with COPD may be partly due to allergic inflammation. PMID- 2099573 TI - Intravascular bronchoalveolar tumor. AB - We report the case of a young woman presenting productive cough and arthralgia in the left ankle. Chest radiography revealed multiple bilateral pulmonary nodules and abdominal echography and computerized axial tomography demonstrated various hepatic nodules. Definitive diagnosis of an intravascular bronchoalveolar tumor was reached by an open pulmonary biopsy. Liver involvement was confirmed by laparoscopy and biopsy. PMID- 2099574 TI - Chylous pleural effusion in tuberous sclerosis. AB - We report on a male patient with tuberous sclerosis (adenoma sebaceum and digital fibromas, renal angiomyolipomas and subependymal brain calcifications), who presented with chylothorax. Chest CT scan did not show pulmonary parenchymal alterations, but only a moderate enlargement of the paracaval mediastinal lymph nodes. Tuberous sclerosis with lung involvement presents clinical, radiologic and pathologic manifestations similar to those of lymphangioleiomyomatosis. The pulmonary manifestations of tuberous sclerosis and lymphangioleiomyomatosis have been observed almost exclusively in women, and it has been suggested that they represent opposite ends of a spectrum of presentations of the same entity. Based on these considerations the formation of a chylothorax in a male with tuberous sclerosis constitutes an extremely rare finding. PMID- 2099575 TI - Detection by ELISA of specific IgG to mycobacterial antigen 60 in a tuberculous exudate. AB - A case of active multicavitary tuberculosis is reported. In the 3rd month of treatment, an X-ray film of the thorax showed right pleural effusion. The properties of the pleural fluid were those of an exudate with high adenosine deaminase activity. An ELISA was performed to detect specific IgG antibody to mycobacterial antigen 60 in serum before the treatment and on a two-monthly basis following the initiation of therapy until completion of the course. Values were all above 1,750 U. Moreover, an ELISA test using the same antigen was done on pleural fluid, and a high IgG titer was obtained (950 U). A cutoff for a positive ELISA test was established at 240 U in serum and 150 U in other biologic fluids. PMID- 2099576 TI - [Basic programs in internal medicine--pro and contra their justification]. AB - Reasons for and against the justification of basis programs in medicine are under world-wide discussion. Due to the different use of relevant terms there are no definite statements in special literature. In this paper an attempt is made to prove the legitimacy of basis programs in internal medicine. The main purpose is to describe the course of actions in medical workday routine. Methodic aspects of the approach to related problems are explained, too. PMID- 2099577 TI - [Insulin and immunology--a correlation]. AB - In comparison to former decenniums the relations between insulin and immunology have changed and continued to develop. Still up to 20 years ago the immunological side effects of an insulin therapy stood well to the fore concerning the clinical interest, nowadays, however, they are the autoantibodies against insulin and it is the role of insulin for a functioning immune system, which is not in the least exactly recognized. PMID- 2099579 TI - [Endoscopic laser therapy in gastroenterology--physical-technical principles and applications]. AB - Since the mid-seventies the application of laser in gastroenterology for the treatment of haemorrhages and tumours has stood the test. At present the neodym YAG-laser is the most important endoscopically applicable laser. The sources of laser radiation, the biophysical effects of laser and their fields of application, the technical and methodical and security-technical aspects as well as own divice-technical solutions and the indications in the application of the endoscopic laser therapy are described. In 12 out of 15 patients with a villous adenoma of the rectum the treatment was successful. In 9 patients with a high degree stenosing rectosigmoid carcinoma (diameter 0.5 cm) the passage could be restored (diameter after treatment 1.3 cm). Complications did not appear. The laser therapy is effective, poor in risks, but not cheap. PMID- 2099578 TI - [Doppler sonography in the diagnosis of extracranial vascular changes]. AB - On account of cerebrovascular insufficiencies or asymptomatic vascular noises which had taken place 45 patients were examined by means of Doppler sonography and after this by means of angiography. The judgement of the common carotid artery, the internal and external carotid arteries, the vertebral artery, the subclavian artery and the supratrochlear artery were involved into the ultrasound investigation. The sensitivity of the supratrochlear compression test was 50% in the diagnosis of high-degree stenoses and occlusions of the internal carotid artery, whereas the sensitivity of the complete ultrasound investigation way about 80%. The advantages and disadvantages of the ultrasound Doppler sonography investigation are discussed. PMID- 2099580 TI - [New aspects of the pharmacokinetics of ethanol]. AB - In the paper a survey on new results in the pharmacokinetics of ethanol is given. Resorption follows the rules of diffusion and is influenced by a lot of factors, this results in a high interindividual variation. Distribution is influenced by a first-pass-effect and the tissue contents of water. Metabolism is performed by alcohol dehydrogenase and microsomal ethanol oxidizing system. The kinetics of ADH is undependent on concentration, the MEOS is inducible. Results of acute and chronic ethanol treatment are discussed, clinical consequences are reviewed. PMID- 2099581 TI - [Possible uses of laser in gastroenterology]. AB - In the therapy of certain benign and malignant changes in the intestinal tract the laser stood the test. The absolute necessity of its use is limited, among others by existing alternative methods, so that a broadly disseminated equipment is not necessary. By the development of new types of laser and better handling systems (fibres with diffuse emission, fibres with lateral delivery of light and so on) its possibilities of application will enhance. PMID- 2099582 TI - [Early prognostic significance of hepatitis B surface antigen specific circulating immune complexes in acute type B viral hepatitis]. AB - A total of 120 patients with acute viral hepatitis B was investigated for the presence of circulating immune complexes, HBsAg-specific immune complexes, and the behavior of some other immune parameters (immunoglobulins, rosette inhibitory factor RIF, histamine induced inhibition of spontaneous rosette forming lymphocytes). Pathologically elevated levels of circulating immune complexes were seen in 89 per cent of patients, often related to extrahepatic signs in the prodromal phase. In 95.7 per cent of them, HBsAg-containing complexes were found. There were no differences in the behavior of immune complexes between patients with recovery and patients developing chronic hepatitis B. On the contrary, the levels of RIF and differences in the inhibitory effect of histamine on rosette forming test of patient's lymphocytes did allow to distinguish patients with recovery from patients with development of chronic hepatitis B early in the course. PMID- 2099583 TI - [Comparative studies of the effectiveness of brief psychotherapy, acupuncture and papaverin therapy in patients with irritable bowel syndrome]. AB - At a comparison among 5 therapy methods the small psychotherapy with a success rate of 74% is high-significantly more prosperous than the other examined methods. The acupuncture with 31% long-term success is significantly superior to the pseudoacupuncture (17.2%). The papaverine therapy results in a long-lasting status free of symptoms in 17.2% of the patients and is significantly different from the results of the papaverine-placebo-therapy (0%). Distinct differences in the success-rates of the small psychotherapy with different therapists prove the role of the personality and the perfection in mastering the methods with psychotherapeutic procedures. Comparable differences between the examiners were not found among the effects of a spasmolytic therapy. PMID- 2099585 TI - Terminal complement complex in plasma of leprosy patients. AB - A study was carried out to find out the difference in the levels of circulating terminal complement complex between healthy volunteers and the untreated leprosy patients by using double antibody sandwich ELISA. In addition, the levels of terminal complement complex in lepromatous patients with and without reaction were also compared. None of the group showed any significant difference in the levels of circulating terminal complement complex. These findings suggest that complement may not play a direct role in tissue damage in leprosy. PMID- 2099584 TI - [Endemic leprosy in the People's Republic of Congo. An epidemiological and behavioral analysis]. AB - The authors report the results of a national prevalence survey of leprosy made in 1989 in Popular Republic of Congo. Leprosy is essentially found in rural areas and frequently causes disabilities. The prevalence rate is 5.8 +/- 2.6% among people more than 15 years of age, and 10.5% of all forms are multibacillary. All patients are under DDS monotherapy. One overwhelming risk factor is leprosy cases in the family history; active case-finding and surveillance of contact cases are recommended. Generally, leprosy is poorly understood by the general population; an educational effort is necessary. PMID- 2099586 TI - Recent advances in restorative surgery of extremities in leprosy. AB - A better understanding of the pathology and mechanisms of nerve damage has changed the plan of treatment of neuritis. A concept of "Preventive Nerve Surgery" has come up during last few years. The genesis of plantar ulcers and its presentation is better understood now. The recent developments in the treatment of paralytic deformities of hand and foot have been outlined. PMID- 2099587 TI - [Synthesis of N2-aryl-triazinoylamoxicillins and N2-phenyl-N4-alkyl (aryl) triazinoylamoxicillins and their antibacterial activity]. AB - Sixteen derivatives of BL-P1908 were synthesized by reaction of 2-aryl-1, 2, 4 triazine -3, 5-dione -6-carboxylic acid, or 2-phenyl-4-alkyl (aryl) -1, 2, 4 triazine-3, 5-dione-6-carboxylic acid with amoxicillin. All of them are new compounds. Their chemical structures were determined by elemental analysis, IR and 1HNMR. Preliminary tests showed that all compounds have marked activities against standard G(+) and G(-) bacteria and five of them have certain characteristic of broad spectrum, but they have no activities against resistant strains S. aureus S1, E coli C1 and P. aeruginosa PS1 isolated from clinic. PMID- 2099588 TI - [Isolation and identification of three new saponins from Phytolacca esculenta]. PMID- 2099589 TI - [Glyyunnanprosapogenin and glyyunnansapogenin from the roots of Glycyrrhiza yunnanensis]. AB - Two new triterpenoidal sapogenins of oleanane type, namely glyyunnanprosapogenin D (V) and glyyunnansapogenin F (IX) were isolated from the roots of Glycyrrhiza yunnanensis Cheng f. et L. K. Tai, family Leguminosae, collected from Yunnan Province, China. V was obtained as hexaacetate and dimethyl ester form (Vc), mp 168-170 degrees C, C56H78O22, which gave an aglycone macedonic acid (V') and two molecules of glucuronic acid after hydrolysis with hydrochloric acid. The spectral analysis of 13CNMR and 1HNMR showed that Vc had two glycoside residues attached to the aglycone, and therefore the structure of V was established as oleana-11, 13(18)-dien-29-oic acid, 3 beta, 21 alpha-di-(O-beta-D-glucuronic acid) pyranoside. IX was obtained as its diacetate and monomethyl ester form (IXc), mp 188-190 degrees C, C35H50O7. The IR, 1HNMR and UV spectra showed that the IXc had a skeleton of oleanane type triterpenoid with heteroannular diene. IXb, diacetate of IX, unpurified, was converted to IXf with chromium trioxide in glacial acetic acid. IXf, mp 160-164 degrees C, C30H46O8, was proved to be olean 12-en-11-oxo-3 beta,24-diacetoxy-18 beta-hydroxy-30-oic acid, 30 in equilibrium 18 beta lactone with another carbonyl group at C-15,16,21 or 22 by the analysis of 13CNMR, 1HNMR and MS spectra.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099590 TI - [Studies on flavonoid constituents isolated from the leaves of Glycyrrhiza uralensis Fisch]. AB - Four flavonoids were isolated from the alcoholic extract of the leaves of Glycyrrhiza uralensis Fisch. (Leguminosae). On the basis of physicochemical properties and spectroscopic analysis their structures were elucidated as 3,5,7,3',4'-pentahydroxy-5'-isoprenylflavone(I), 3,6,7,3',4'-pentahydroxy-2' isoprenylflavone(II) and 5,7,3',4'-tetrahydroxy-5'-isoprenyl-flavonone(III) and quercetin-3,3'-dimethylether(IV). Compounds I, II and III are new compounds and named uralenol, neouralenol and uralenin respectively. Compound IV was found in this genus for the first time. Compound III was shown to be the major constituent in the leaves of Glycyrrhiza uralensis Fishch. PMID- 2099592 TI - [Photodecomposition of artificial calculus bovis]. AB - Artificial calculus bovis (ACB) is widely used in dispensing Chinese Traditional Patent Medicine as a substitute for Calculus bovis. Photodecomposition rule of ACB sample irradiated with three different light sources was studied by diffuse reflectance spectrophotometry (DRS) in this paper. The results show that, the photodecomposition rate curves of the ACB sample irradiated by all three light sources are composed of two straight lines of different slopes, indicating that they are of two-step apparent first order reaction, the apparent photodecomposition constants in the first steps are about twice as high as those in the second steps. The ACB sample has the fastest photodecomposition rate when irradiated with the UV mercury-arc lamp and the second with the fluorescent mercury-arc lamp and slowest with the iodine-tungsten lamp. In these three light sources apparent photodecomposition constants of ACB sample are respectively: K1, 2.7629 x 10(-5), 4.4132 x 10(-6); k2, 1.2176 x 10(-5), 2.0684 x 10(-6), 1.4357 x 10(-6) (lx-1.h-1). The apparent constants are independent of the product of the radiation intensity and the irradiation time, but the irradiation time is in inverse ratio of the radiation intensity to get the same proportion of the sample photodecomposition. The fading time of the ACB sample under different radiation intensity can be predicted with the kinetic equations reported. The fading time of ACB sample if directly exposed to light in bright room is 1.6 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099591 TI - [Assay of bilirubin of ox gallstone in Chinese patent medicines by differential spectrophotometry]. AB - This paper describes that the absorption spectrum of bilirubin solution was changed obviously by photo-oxidation. The absorbance was measured at 453 nm before and after light irradiation. The contents of bilirubin of ox gallstone in Liuying pills, Liushen pills and Niuhuang Xiaoyan pills were determined by differential absorbance (delta A). Calibration graph was linear in the range of 1.6-8.0 micrograms/ml for delta A. The average recoveries for three Chinese patent medicines were over 93%. Determinations of bilirubin in Chinese patent medicines were not affected by other components. PMID- 2099593 TI - [Use of 2H-labeled compound and GC-MS in the isolation and identification of a metabolite of biphenyldimethyl-dicarboxylate in rat urine]. AB - Dimethyl-4, 4'-dimethoxy-5, 6, 5', 6'-dimethylenedioxy-biphenyl-2, 2' dicarboxylate (biphenyldimethyldicarboxylate; BDD), a synthetic compound, has been used in the treatment of chronic hepatitis with good results in reducing s GPT. Previous work in our laboratory studied its metabolites using 3H-labeled compound in combination with TLC and found that its main metabolic pathway is demethylation followed by conjugation with glucuronic acid. This paper reports the isolation and identification of a metabolite of BDD from rat urine using 2H labeled compound and GC-MS. Rats fasted for 12 h were intragastrically given a mixture of 2H-labeled (consisting of monodeutero- and dideutero-BDD in the ratio about 1:1.3) and non-labeled BDD 150 mg/kg and placed in metabolism cages for urine collection. The 24 h urine was filtered and extracted three times each with 5 ml of methylenedichloride. The extracts were pooled and evaporated to dryness under reduced pressure at 35 degrees C. The residue was redissolved in chloroform and subjected to GC-MS analysis. The mass spectrum (m/z: 404, 405, 406; 373, 374, 375; 345, 346, 347; 330, 331, 332; etc) indicates that the molecular ionic and fragment peaks of the metabolite all have 14 amu less than those of BDD. This means that the metabolite isolated is mono-O-demethylated BDD. The result confirmed our findings reported previously. PMID- 2099594 TI - [Alkaloids with cardiovascular activities--synthesis of protoberberine]. AB - It has been reported that berberine (BR) has positive inotropic and negative chronotropic effects. Recently, it has been tried in patients with arrhythmia and congestive heart failure. But BR, a quaternary ammonium salt, is absorbed poorly. We took BR as leading compound to synthesize its derivatives in order to find orally active agents. Compounds substituted by -OCH3 in different positions of the D ring were synthesized. In the screening of inhibition of electrically induced contraction of isolated guinea pig left atria and spontaneous beating of its right atria, the synthesized compounds were found to possess activity of inhibiting spontaneous beating of isolated guinea pig right atria. Compound I4 was shown to be the most effective of the synthesized compounds with IC50 value of 4.34 (mumol). The IC50 value of BR was 204 (mumol). PMID- 2099595 TI - [Studies on antitumor drugs: the synthesis of N',N"-dispirotripiperaziniums]. AB - In order to search for new antitumor drugs, sixteen N',N"-dispirotripiperazine derivatives were synthesized from N',N"-dispirotripiperazinium dichloride dihydrochloride by substitution, acylation and Mannich reaction. Six compounds were selected for preliminary pharmacological test. The result showed that five compounds possess inhibitory action against carcinoma S37 in rats. The inhibitory activity of compounds VI and X was 55.0% and 41.9% respectively. PMID- 2099596 TI - [Studies on uranium mobilization agents. IV. Synthesis of N, N'-bis-[N carboxymethyl-(2,3-dihydroxy-5-carbomethoxy) benzylaminoacetyl]-alpha, omega diamines]. AB - In continuation of searching for effective antidotes against uranium intoxication, a series of N,N'-bis-[N-carboxymethyl-(2,3-dihydroxy-5 carbomethoxy) benzylaminoacetyl]-alpha, omega-diamines was synthesized by reacting 2,3-dihydroxy-5-carbomethoxybenzylamine diacetic acid with diamines of different chain lengths. Their effects on the elimination of uranyl nitrate from rats were tested. Most of them were found to be more effective than the reported uranium chelating agents as Tiron and Phosphicine and compound IIa was shown to be the most promising. The results of pharmacological studies will be published elsewhere. PMID- 2099597 TI - [Isolation and identification of yibeinoside A]. AB - Two steroidal alkaloids were isolated from the bulb of Fritillaria pallidiflora Schreb by column chromatographic techniques. One of them was identified as known alkaloid sinpeinine A, another alkaloid was found to be a new compound named yibeinoside A, which is the Sinpeinine-3-O-beta-glucoside. Its structure was confirmed on the basis of chemical and spectral data (IR, MS, 1HNMR, 13CNMR). PMID- 2099598 TI - [Studies on the structure of a new ellagic acid glycoside from the root-sprouts of Agrimonia pilosa Ledeb]. AB - Four compounds were isolated from the root-sprouts of Agrimonia pilosa Ledeb. On the basis of physico-chemical properties, spectroscopy (UV, IR, NMR, MS) and chemical degradation, a new compound was elucidated as ellagic acid-4-O-beta-D xylopyranoside (XV), and three known compounds were identified as agrimonolide (XIII), tormentic acid (XIV), and ellagic acid (XVI). PMID- 2099599 TI - Damages to feed proteins and their nutritional consequences: a review. AB - The consequences of heat processing of feeds for sterilization and to destroy antinutritive substances can be beneficial as well as detrimental. Damages to feed proteins may be primarily explained by complex reactions between proteins and carbohydrates, by interactions between protein molecules and by oxidation. The chemical mechanisms and nutritional consequences of these reactions are reviewed. PMID- 2099600 TI - Optimizing protein quality of mixtures of blood meal, feather meal and bone meal. AB - The protein quality of two- or three-component mixtures of blood meal, feather meal and bone meal was characterized by amino acid scores and rat net protein utilization (NPU) values. A graphic method designed to find optimum levels of the limiting essential amino acids in the mixtures was suitable for predicting the optimum of NPU values determined by feeding rats with diets having 10% crude protein. The protein quality of mixtures of blood meal, feather meal and bone meal showed an optimum if blood meal constituted 60% of the protein content of the mixtures; however, poor feed intake and growth data were obtained. PMID- 2099601 TI - Evaluation of the energy value of rabbit feeds: a critical review. AB - An analysis is given of the methods actually used for the determination and calculation of the energy value of rabbit feeds and feedstuffs. The apparent digestible energy (DE) system is recommended. Standardization of the applied methodology for in vivo determination is emphasized. Four to six ad libitum fed growing rabbits are necessary to obtain sufficiently accurate results. The reliability of the estimation of the feeds' energy content, based on the table values of the ingredients, is discussed. The importance of using recently and properly determined data is stressed. Multiple regression equations, based on the results of the chemical analysis of feeds, explain 85-90% of the variability of DE content. The first attempts with in vitro techniques are encouraging. PMID- 2099602 TI - The effect of animal fat and vegetable oil supplementation of feeds of different energy concentration upon the digestibility of nutrients and some blood parameters in rabbits. AB - The effect of mixed animal fat and sunflower oil supplementation (5%) of a feed of medium (12.02 MJ DE/kg) and low (8.54 MJ DE/kg) energy concentration upon the digestibility of nutrients and on some blood parameters was investigated. The ether-extractable content of feed and faecal samples was determined by diethyl ether extraction (after Soxhlet) and the total (true) fat level was measured by the method of Stoldt (1952), viz. petroleum ether extraction of samples pretreated with 4 N HCl. In the majority of cases the voluntary feed intake decreased after the addition of animal fat or vegetable oil. Mixed animal fat supplementation significantly (by 5 and 11 units) improved the digestibility of the ether extract if added to either of the basal diets. The digestibility of crude fibre and N-free extract increased only in the case of the basal diet of low energy concentration (by 4 and 7 units, respectively). Sunflower oil addition produced changes of the same tendency (9, 9, 28 and 5 units). The digestibility of the crude protein was practically not altered by either supplementation. The total fat content of feed and faecal samples proved to be higher than that of the ether extract, on an average by 27 and 100%, respectively. Consequently, the digestibility coefficients of the total fat are by 10 units lower than those of the ether extract. The DE concentrations, calculated by means of the digestible ether extract or the total fat content, differed significantly only between the basal diets. The addition of mixed animal fat to either of the basal diets increased the blood concentration of total lipids (by 18 and 32%, respectively), while that of sunflower oil did not cause such an alteration. Neither fat nor oil supplementation had an effect on the cholesterol level of the blood plasma. Both the animal fat and the vegetable oil surplus modified the fatty acid composition of blood lipids. It was characteristic of each treatment that the proportion of polyunsaturated fatty acids increased. PMID- 2099603 TI - Treatment of anoestrous mares with a synthetic progestagen, allyloestrenol. AB - Anoestrous mares were treated with prostaglandin (n = 43) and those that did not respond to prostaglandin (n = 29) with a synthetic progestagen, allyloestrenol, at a dose of 0.05 mg/kg body mass for 12 days. After the cessation of the long term per os gestagen blockade the animals were checked for heat and, if a preovulatory follicle could be palpated, 2000 IU hCG was administered to induce ovulation. In some animals the plasma 17 beta-oestradiol (E2) and progesterone (P4) levels were also followed up throughout the gestagen treatment and for 10-14 days thereafter. As the favourable oestrus rate (86.2%) and pregnancy rate (65.5%) indicate, the 12-day allyloestrenol treatment seems to be a reliable tool for induction of cycling in mares anoestrous early in the season. These results, supported by the E2 and P4 profiles, suggest that an important reason for anoestrus in mares is the absence of a functional corpus luteum that can be substituted for by exogenous gestagen administration. The timing of ovulation, however, should still be improved. PMID- 2099604 TI - Gas chromatographic characterization of the relationship between some Mycobacterium avium and Mycobacterium paratuberculosis strains. AB - Mycobacterium avium strain P-55 and M. avium strain DENT differ from M. avium strain 16909-338 on the basis of their fatty acid spectra (C14:0, C18:0 and tuberculostearic [TBS] acids) studied by multivariate statistical analyses. Strains P-55 and DENT are closer to M. paratuberculosis strain 5889 than to M. avium strain 16909-338, a finding which is in harmony with earlier immunological observations. The recently isolated M. paratuberculosis strain 385 has proved different from M. paratuberculosis strain 5889. PMID- 2099605 TI - Immunopathological changes in mice caused by Bordetella bronchiseptica and Pasteurella multocida. AB - The immunopathological changes induced by toxigenic Pasteurella multocida, toxigenic phase I Bordetella bronchiseptica and its phase III variant were studied. Four groups of mice, each containing 21 animals, were inoculated intravenously with sublethal doses of B. bronchiseptica as follows: group 1: phase I toxigenic B. bronchiseptica whole-cell suspension (WCS); group 2: phase III B. bronchiseptica WCS; group 3: phase I B. bronchiseptica sonicated extract (SE); and group 4: phase III B. bronchiseptica SE. The fifth group received SE of toxigenic P. multocida. Lymphatic organs, lungs, livers and testes from three mice per group were examined histologically on every second day of a two-week period. In the spleen of mice, where the so-called lienotoxic effect manifested itself (groups 1, 3, 4 and 5), the percentile proportion of lymphoblasts significantly decreased in both the B and the T cell dependent areas. The lymph nodes also showed a reduction in the number of lymphoblasts. The reduction in spleen mass was partly attributable to a drastic decrease in the number of megakaryocytes and of blast cells participating in physiological extramedullary haematopoiesis in the red pulp. Opposite changes were demonstrable in group 2 the mice of which showed splenic hypertrophy. PMID- 2099606 TI - The pathology of experimental respiratory infection with Pasteurella multocida and Bordetella bronchiseptica in rabbits. AB - Groups of female New Zealand White rabbits, 8-10 weeks old, were inoculated intranasally with three different Pasteurella multocida serotypes (A:3, A:4 and A:12) or one of three Bordetella bronchiseptica strains of rabbit origin. Seven out of 18 rabbits died of experimental infection with P. multocida. B. bronchiseptica killed 3 out of the 8 animals inoculated with it. Deaths occurred between 3 and 6 days postinoculation (PI). In the rabbits that died of P. multocida inoculation, necropsy and histology revealed severe pleuritis with the accumulation of a remarkable amount of fibrinopurulent exudate in the thoracic cavity, serous rhinitis and tracheitis, acute hepatitis with necrotic foci in the parenchyma, and atrophy of the lymphoid organs and tissues. Rabbits killed 10 days PI developed only subacute serous rhinitis and hyperplasia of the lymphoid tissues. Rabbits that died of B. bronchiseptica inoculation showed acute serous rhinitis, acute catarrhal-fibrinopurulent pneumonia and mild pleuritis. As opposed to P. multocida inoculated animals, hepatitis and atrophy of the lymphoid tissues were not characteristic of these rabbits. Rabbits killed 10 days PI developed subacute purulent and necrotic pneumonia with remarkable macrophage proliferation, involving all lobes, and hyperplasia of the lymphoid tissues. PMID- 2099607 TI - Changes in the serum levels of primary bile acids in dairy cows. AB - Serum cholic acid (SCA) and serum chenodeoxycholic acid (SCDCA) concentrations were determined in healthy dairy cows by radioimmunoassay (RIA). The levels of these two primary bile acids were correlated with the cows' reproductive status. The lowest concentrations were measured in dry cows (SCA: 7.8 +/- 3.3 mumol/l, SCDCA.: 1.5 +/- 1.0 mumol/l). In freshly calved cows SCA and SCDCA was 17.8 +/- 6.9 mumol/l and 2.3 +/- 1.0 mumol/l, respectively, while in milking cows SCA and SCDCA was 15.8 +/- 5.7 and 2.3 +/- 0.8 mumol/l, respectively. SCA concentration showed a characteristic change on the days immediately after calving: on calving day it was close to the mean SCA concentration found for dry cows, then it underwent a striking abrupt rise and reached the value typical of post-parturient cows by post-partum (PP) day 4-5. Cholic acid was found to be the major primary bile acid in the blood of dairy cows. In dry cows the SCA:SCDCA ratio is 5:1. If the serum bile acid concentration rises, the SCA:SCDCA ratio will increase further. PMID- 2099609 TI - Survey of Actinobacillus (Haemophilus) pleuropneumoniae infection in swine by different methods. AB - Lung and serum samples from pigs that died or were emergency-slaughtered in a pooled, conventional fattening herd were examined to survey Actinobacillus pleuro pneumoniae infection and to compare the sensitivity of different testing methods. A total of 110 lungs were used for cultural isolation of the agent and direct immunofluorescence (IF) of impression smears. Boiled lung suspensions were tested by coagglutination (Co-A) and agar gel precipitation (AGP). Eighty-seven sera were tested along with lung samples from the same pigs. The lungs yielded a varied bacterial flora most often containing Pasteurella multocida and less frequently Actinomyces (Corynebacterium) pyogenes, E. coli and Salmonella. A. pleuropneumoniae was isolated from 30 lungs: from 22 lungs it grew out in pure culture, from 7 as mixed culture with P. multocida and from 1 as mixed culture with A. pyogenes. The number of positive samples obtained by the different methods was as follows: coagglutination test (with boiled lung suspensions): 63 (57.3%); immunofluorescence: 43 (39.2%); AGP test (with serum): 31 (35.6%); AFP test (with boiled lung suspension): 25 (22.7%). A total of 23 samples (20.7%) were negative by all serological tests and by cultural isolation. Most samples gave positive results by two or more tests while 26 samples only by one test (most often, on 13 occasions, by the Co-A test). The Co-A test detected antigenic components of serotypes that have not been isolated in Hungary so far. This indicates that it is not enough to test one strain from a given lung sample: several colonies must be cultured and serotyped.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099608 TI - Characterization of Actinobacillus strains isolated from aborted swine fetuses. AB - Eleven Actinobacillus strains were isolated in pure culture from 12- to 13-week old aborted swine fetuses. Apart from minor biochemical differences, they resembled strains isolated from sow vaginas by Ross et al. (1972) in the U. S. A. Some of the strains agglutinated sheep, cattle and horse but not pig, dog and chicken erythrocytes. Haemagglutination was mannose resistant and could be inhibited by specific hyperimmune serum. Heating above 70 degrees C diminished or abolished haemagglutination of the cultures. Electron microscopy showed no fimbriae on the surface of the bacteria. PMID- 2099610 TI - Occurrence of monogeneans on freshwater fishes in Iran: Dactylogyrus spp. on cultured Iranian fishes. AB - Thirteen Dactylogyrus spp. were found on cultured fishes in five Iranian fish farms. Besides typical Dactylogyrus vastator, specimens with small anchors were often found in goldfish, which were designated as D. vastator forma minor. Rutilus frisii kutum, a fish cultured only in Iran, was infected by two Dactylogyrus spp. during its short period of prerearing in Iranian fish farms. All Dactylogyrus found are new for the Iranian fauna. PMID- 2099611 TI - Effect of benzimidazoles on amino acid metabolism in Trichuris globulosa. AB - L-aspartic acid C14, L-alanine C14 and L-leucine C14 uptake by Trichuris globulosa was found to be a non-linear function of time and limiting substrate concentration. The uptake was rapid initially but achieved steady state possibly owing to the saturation of transport loci. Linear transformations of substrate saturation kinetics by Lineweaver-Burk plots of L-aspartic acid C14, L-alanine C14 and L-leucine C14 gave Kt values of 6.8 X 10(3) microM, 3.4 X 10(3) microM and 6.06 X 10(3) microM and Jmax of 0.769 mumoles/mg dry weight/min, 10 mumoles/mg dry weight/min and 0.285 mumoles/mg dry weight/min, respectively. The presence of benzimidazole drugs, thiabendazole and fenbendazole, markedly inhibited the uptake of amino acids at concentrations which did not affect the motility of the parasite. The amino acid transport was also found to be pH and temperature dependent. The uptaken amino acids were readily metabolized into different tissue fractions. Thiabendazole and fenbendazole significantly inhibited the incorporation of the three amino acids into the nematode's total protein fractions and trichloroacetic acid soluble fractions. These drugs also decreased the amount of radiocarbon of 14C-amino acids incorporated into CO2. PMID- 2099612 TI - Changes in the lipid peroxide status of broiler chickens in acute monensin poisoning. AB - The effect exerted by overdosage of monensin, an ionophore antibiotic, on the lipid peroxide status of broiler chickens was studied. Three-week-old broiler cockerels were given 150 mg monensin/kg body mass through a tube, and the malondialdehyde (MDA) concentration, glutathione peroxidase (GSH-Px) and catalase activity of the liver and breast muscle, and MDA concentration and GSH-Px activity of the blood plasma were determined. Liver MDA and catalase values rose rapidly and significantly during the experimental period. GSH-Px activity initially decreased, then tended to rise. Blood plasma and breast muscle variables did not change during the experiment. Acute monensin poisoning induced substantial enhancement of lipid peroxidation processes in the liver, while it did not appreciably affect the lipid peroxide status of the blood plasma and breast muscle. The role of the observed phenomenon in the rather complex pathogenesis of monensin poisoning is not known sufficiently. Further studies are needed to elucidate the problem. PMID- 2099613 TI - Toxicological and biological studies on Japanese quails fed graded levels of furazolidone. AB - Furazolidone (FZ) was administered to 42-day-old female Japanese quails as a feed additive at doses of 0, 200, 400, 600 and 800 ppm for a period of 28 days. Dose dependent effects were observed. High levels of FZ (600 and 800 ppm) significantly altered growth, decreased feed consumption, caused marked atrophy of the ovaries and oviducts leading to cessation of egg laying, and resulted in higher mortality. Hepatotoxicity was evidenced by an increase in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase and a decrease in serum total protein, in addition to degenerative changes of the hepatocytes in FZ-treated birds. A rise in serum urea was also observed. Symptoms leading to death included a loss of appetite causing emaciation followed by nervous disturbances (compulsive movements and circling). No signs of cardiomyopathy were observed. Japanese quails did not tolerate FZ at a concentration (400 ppm) recommended for the prevention of salmonellosis in poultry. PMID- 2099614 TI - Alternating one-letter symbols for the representation of codon variations at the level of amino acid sequences. AB - An idea is presented to use different letter types (e.g. L. 1, L, 1, L, l) for the alternating triplets coding the same amino acids. Such compact and demonstrative amino acid sequence comparisons can make easy the identification of differences at the DNA level if not seen in amino acid sequences (e.g. for choosing specific or non-specific primers for polymerase chain reaction). PMID- 2099615 TI - Structural variation in the nasal bone region of European moose (Alces alces L.). AB - The ontogeny of typical (normal) nasal bone region of the European moose (Alces alces L.) and the 3 variants of the pattern, was studied. The variants, named as "extra bone type", "punctured type" and "open type" referring the morphology of the internasal suture, were originally observed in Finnish male and female moose skulls in 1971. All of the variants were later found in hunting trophy exhibitions presenting male moose trophies from Sweden, Norway, Baltic Republics of USSR and Poland. The frequencies of the variants showed regional differences. By using histological, radiological and OTC bone labelling methods, all of the nasal bone types were observed in this study in embryonal (N = 36), newborn (N = 21), juvenile (N = 38) and adult (N = 12) moose. Two twin embryos showed different nasal bone structure. The variation is considered to be of congenital origin. PMID- 2099616 TI - Embryonation and infectivity of Ascaris suum eggs. A comparison of eggs collected from worm uteri with eggs isolated from pig faeces. AB - Ascaris suum eggs were collected from pig faeces or dissected from worms obtained from the same pigs. Eggs from the two sources were allowed to embryonate in 0.1 N H2SO4, in 1% buffered formalin or in tap water. The embryonation of the sulphuric acid and water cultures occurred at the same speed, while the formalin cultures developed slightly more slowly. By experimental inoculation of helminth-free pigs and subsequent counting of white spots in the livers and larvae in the lungs day 7 p.i., the infectivity of eggs dissected from worm uteri and embryonated in sulphuric acid (a normal laboratory procedure) was compared with that of eggs collected from faeces and embryonated in water (i.e. more naturally developed eggs). The results suggest that the two types of eggs were equally infective. For this reason the common practice of using Ascaris eggs dissected from worms for experimental infections might be acceptable. PMID- 2099617 TI - Response of whole blood, erythrocyte and plasma vitamin E content to dietary vitamin E intake in the chick. AB - Whole blood, red blood cells (RBC), and plasma vitamin E (VE) levels in chicks fed dietary VE (dl-alpha-tocopheryl acetate, dl-alpha Ta) supplementation in steps of 0.0, 5.0, 10.0, 15.0, 20.0 and 30.0 mg/Kg were determined to examine their usefulness as an index of VE status. The increase in VE level was significant and linear in whole blood (r = 0.90), RBC (r = 0.89) and plasma (r = 0.93) in response to dietary VE intake. There was a close correlation between VE in plasma vs whole blood (r = 0.90), plasma vs RBC (r = 0.91) and whole blood vs RBC (r = 0.95). The plasma VE content was 1.2-1.8 times greater than that of whole blood, and 6.6-12.5 times greater than that of RBC. The plasma total lipids content was not affected by the dietary VE intake, whereas the level of VE in the plasma total lipids was significantly increased with increasing supplementation. Alpha tocopherol was the major isomer (ca 92%) of VE in whole blood, RBC and plasma at hatching. The small proportions of beta-tocopherol (ca 2%), gamma tocopherol (ca 5%) and alpha-tocotrienol (ca 1%) observed at 1 day of age had decreased or totally disappeared by 7 days of age after feeding the VE-free basal diet. The data showed that in the chick, the whole blood and RBC levels of VE were as sensitive and reliable indexes of dietary VE status as was that of the plasma. PMID- 2099618 TI - Attempts to transfer Elaphostrongylus alces from moose (Alces alces) to sheep and goats. AB - Six 1 year old female and 6 four months old male goats were inoculated different numbers of E. alces third-stage larvae. Protostrongylid larvae were not detected in the faeces of these animals during the experiment. At the end of the experimental period the animals were euthanized and autopsied. Neither parasites nor pathological lesions related to larval or adult stages of E. alces could be demonstrated. PMID- 2099619 TI - Evaluation of ELISA for the detection of Toxoplasma antibodies in swine sera. AB - Enzyme-linked immunosorbent assay (ELISA) is compared with the indirect fluorescent antibody test (IFAT), the indirect haemagglutination test (IHAT) and the latex agglutination (LA) test for the detection of toxoplasma antibodies in swine sera. The 100 swine sera examined represent ELISA values from greater than 0 to 154 EIU. The agreement was highest (0.67) between ELISA and IFAT with an ELISA cut-off value of 30 EIU, and between ELISA and the LA test with an ELISA cut-off value of 50 EIU (0.74). All sera giving less than 10 EIU were negative in the other tests, and all those with greater than 70 EIU were positive in 1, 2 or all of the reference tests. In order to avoid false positive results with ELISA, all sera giving 10-70 EIU should be confirmed with a test which has a good specificity, e.g. IFAT. ELISA is a sensitive test and is highly suitable for the screening of large amounts of samples, but it may be too complicated for screening toxoplasma antibodies in the laboratories of abattoirs. PMID- 2099621 TI - Milk and serum progesterone levels in mares after ovulation. AB - Twenty-four Finnhorse mares were examined by rectal palpation and ultrasonography every 6 h during late oestrus to determine the time of ovulation. Milk and serum samples were collected every 6 h after the detected ovulation for progesterone analysis. The progesterone rises took place within 0-54 h and 0-60 h after ovulation, in milk and serum, respectively. Statistically significant differences (p less than 0.05) in progesterone levels were observed for the first time 12-18 h and 18-24 h after ovulation, in serum and milk, respectively, as compared to progesterone levels 0-6 h after ovulation. PMID- 2099620 TI - Ketosis treatment and milk yield in dairy cows related to milk acetoacetate levels. AB - Milk yield and milk acetoacetate (M-acac) were measured weekly for the first 6 weeks of lactation in 5 herds with a ketosis problem. Ketosis treatments and the corresponding ketotest score, were also recorded. The treatment rate was highest 7-16 days after calving. Most of these early cases were associated with low ketone levels in milk, whereas the treatment rate for cows with high ketone levels was highest 17-31 days after calving. Nearly half of the treated cows were low-ketone animals. They were classified as ketosis cases in the cow health card records, although probably suffering from other post partum disturbances in many instances. About 40% of the cows with high ketone levels recovered spontaneously. Reduction in milk yield associated with peak M-acac levels was transient and moderate. It was concluded that health card statistics overestimates the severity of the ketosis problem in Norway. PMID- 2099622 TI - Immuno-histochemical and -cytochemical evidence suggesting the presence of Campylobacter jejuni and Campylobacter coli in cases of porcine intestinal adenomatosis. AB - Antisera against a number of Campylobacter species were used in immuno histochemical and -cytochemical studies on cases of porcine intestinal adenomatosis. Avidin-biotin-complex (ABC) and streptavidin immunoperoxidase methods were used on formalin-fixed, paraffin-embedded and frozen sections. Protein A gold method was used on formaldehyde fixed and frozen sections for immuno-cytochemistry. The antisera used were raised in rabbits by subcutaneous or intravenous injection of living or formalin treated organisms. Anti-sera against different serotypes of the thermotolerant, catalase positive campylobacters, Campylobacter jejuni and Campylobacter coli, gave positive reactions in the immuno-histochemical studies. The staining was found in intestinal epithelial cells both in the ileum and in the colon and was restricted to the apical cytoplasm of adenomatous epithelial cells. The staining had a granular pattern, the positive structures sometimes having the shape of Campylobacter. Epithelial cells in areas with normal differentiation of goblet cells did not stain. In contrast, no staining resulted with antisera against Campylobacter sputorum subsp. mucosalis and Campylobacter hyointestinalis. Immuno-cytochemistry, using antisera against Campylobacter jejuni, showed that the positive staining in altered epithelial cells were restricted to intracellular organisms having a structure resembling Campylobacter spp. PMID- 2099623 TI - Effect of feeding on reproductive performance in Finnish dairy cows. AB - The effect of 2 types of feeding on the involution of the genital tract and on the fertility was studied in 79 Finnish dairy cows on a research farm. The cows were fed twice a day with home-produced feed in accordance with the Finnish feeding standard. The cows were divided according to the type of feed into a hay urea group and a silage group. The cows were examined clinically by rectal palpation 3 times a week during 8 weeks postpartum. The time required for the complete involution of uterus and cervix was recorded. The cows in the silage group had a significantly longer time in uterine involution, a lower fertility rate at first insemination and a longer interval from calving to conception than those in the hay-urea group. The pregnancy rate in the first insemination was in the hay-urea group 91% and in the silage group 57%. The interval between calving and the first insemination was shorter in the hay-urea group than in the silage group: 71.4 +/- 10.6 and 74.0 +/- 10.3 days, respectively. The interval between calving and conception was in the hay-urea group significantly (p less than 0.01) shorter than in the silage group; 74.8 +/- 15.1 and 89.5 +/- 24.4 days, respectively. PMID- 2099624 TI - Bovine steroid hormone and SHBG concentrations postpartum and during the oestrous cycle. AB - Changes in consecutive estimates of milk progesterone concentrations and serum steroid hormone and sex hormone-binding globulin (SHBG) concentrations in the postpartum period were examined in Finnish Ayrshire and Friesian dairy cows which were divided according to feeding into a hay group and a silage group. Milk progesterone concentrations rose above 10 nmol/l, indicating the start of ovarian luteal activity, slightly earlier in the silage group (28.4 +/- 8.7 (S.D.) days, n = 19) than in the hay group (33.4 +/- 10.3, n = 28) after calving. Likewise, the first normal oestrous cycles began slightly earlier in cows fed with silage. On the other hand, no differences in the beginning of ovarian luteal activity were observed between the breeds. Serum oestradiol-17 beta, oestrone, testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), pregnenolone and progesterone concentrations were fairly unchanged during postpartum anoestrus after uterine involution and before ovarian cyclic activity. After first ovulation, considerable increases in milk and serum progesterone concentrations were observed. The increase was accompanied by elevations in serum pregnenolone and 5 alpha-DHT concentrations. In the late luteal phase, progesterone, 5 alpha DHT and pregnenolone concentrations rapidly declined, leading to low hormone levels in pro-oestrus. Thereafter, serum pregnenolone and 5 alpha-DHT concentrations slightly increased during the follicular phase. On the other hand, oestradiol-17 beta concentrations were elevated in pro-oestrus and decreased after that, being lowest at met-oestrous. Serum testosterone concentrations appeared to be unchanged during postpartum anoestrus and over the oestrous cycle. Serum SHBG concentrations were unchanged during postpartum anoestrus and over the oestrous cycle, as well as in pregnant animals. The serum SHBG concentrations were about double those found in women with normal menstrual cycles, whereas oestradiol concentrations were much lower. At present, it cannot be explained how the biological effects of oestradiol become evident under such conditions. PMID- 2099625 TI - Tramped teats--clinical mastitis disease complex in tied cows. Environmental risk factors and interrelationships with other diseases. AB - The effects of stall length, manure system, type of bedding and calving disorders on incidence rates of tramped teats, udder injuries, and clinical mastitis in Swedish Red and White tied cows, as well as interrelationships between these 3 disorders were investigated. Data used consisted of 370 herds, for a total of 45,133 cow records. Cows in herds with liquid manure system were at higher risk of udder injuries and mastitis than in herds with solid system. Lower risk of both udder injuries and mastitis was found for cows in herds with short stall size (less than 180 cm) compared to herds with stalls of 205-219 cm length. It was suggested that other factors, such as slipperiness of the stall floor and presence and type of feeding barrier, must be considered when the effect of stall characteristics on tramped teats is investigated. In farms with solid manure system cut straw or sawdust bedding increased the risk of tramped teats and mastitis relative to uncut straw. Parity and calving disorders were important risk factors for udder health and their effect was greater in herds with liquid manure system. Tramped teats and udder injuries were the most serious risk factors for clinical mastitis. PMID- 2099626 TI - Ascaris suum: influence of egg density on in vitro development from embryonated egg to infective stage. PMID- 2099627 TI - Demonstration of Pasteurella multocida type 6:B (B:2) in formalin-fixed paraffin embedded tissues of buffaloes by the peroxidase anti-peroxidase (PAP) technique. PMID- 2099628 TI - Feeding reduced the absorption of erythromycin in the dog. PMID- 2099629 TI - Clinical and blood biochemical changes during induction of endotoxaemia in heifers. PMID- 2099630 TI - Effects of testosterone and LH concentrations of induced testicular degeneration in bulls. PMID- 2099631 TI - Effects of oyster mushroom Pleurotus pulmonarius on preparasitic larvae of bovine trichostrongyles. PMID- 2099633 TI - [Introductive remarks on ICU team]. AB - What makes a team efficient? Because the components which lead to its functioning as a whole have changed over recent years, the very concept of a team is to be analysed. PMID- 2099632 TI - [Post-surgical resuscitation facts]. AB - Intensive care fact, especially patients subjective experiences, can be approached as a specific object, a particular stakes and states model, beyond varied peculiarities of clinical fields which are concerned (head traumas, grafts etc..). Intensive care psychical aspects concern psychical trauma ("intensive care hole"); archaic, original, psychotic and distress experiences by grown-up and infants; persecution; unexpected memory; those who "get over far from". They have therapeutic implications with patients and with nursing team. PMID- 2099634 TI - [To be or not to be]. AB - It's all about life in an intensive care unit. Of course, there is an organic aspect of life, the maintenance of which relies on a knowledge. Playing with a human being, life relies also on a psychological aspect and the temptation is great to answer the problematical by knowledge as well. But such an attitude would be most inoperative. It could only serve the therapeutist in economizing his own psychological engagement in the relation with the patient. In the confrontation between patient and therapeutist, isn't it rather a question of existential work between two protagonists during which the patient would be fighting for the maintenance or the restitution of his own person, while the therapeutist tries to maintain his. PMID- 2099636 TI - [Coma, dream and thinking: a semiotic approach]. AB - The notion of "frontier-dream", with a high perceptive direct content, is defined from accounts of dream experienced during coma. Then, from discussions with nursing-team working in units for comatose patients in a wakeful state, a protocol is proposed based on semiotic and psychoanalytical factors which aims at ensuring the global care of the comatose patient considered as a person. PMID- 2099635 TI - [Semiotic of awakening from coma]. AB - One neurosurgeon and two semioticians compare their approaches on the awakening from deep coma. Successive stages of reorganization of possibilities of communication are analyzed. This new vision of coma seems pregnant of new issues. PMID- 2099637 TI - [Psychological management in critical care units. History of a long way]. AB - Some concepts of the General Systems Theory issued from the Social Sciences are used by Liaison psychiatrist and psychologist in the Intensive Care Unit. Human system, interaction process and circular causality, all concepts from the Systemic approach, are useful in order to describe and analyse both vital and existential crisis situation of the patient. As an expansion of the therapeutic context, the relationship among the patient, the family and the medical team are defined in terms of a partnership instead of a power conflict. Then, attention is focused on the distress resulting from these stressful situations, influenced by the "pangs of death". Emphasizing the importance and the role of anxiety allows to recognize a place for it and to offer to everybody an opportunity to talk about it. Finally, the psychotherapeutic function can be defined as the creation of a place given to the person as a Subject, based on the recognition of the fundamental misunderstanding of human illness. PMID- 2099638 TI - [Traumatic coma awakening unit]. AB - Clinique Saint Martin is a specialized center for neurologic reeducation which disposes since the month of May 1989 of a ten beds unit intended to receive head injury during coma awakening stage (as soon as possible after intensive care). Effectively important clinical troubles are in relation with traumatism and coma but also secondary effects seems to be due to a long stay in Intensive Care Unit (in spite of all qualities of the medical team). Every patient has a room which can be personified and become very familiar for purpose to create a safe surrounding, without movement limitation and rich in sensorial stimulations and human contacts. Team for each patient is very numerous. In very intensive and permanent way the first period is distinguished by the need of a presence. Repeated calls "for nothing" are characteristic of coma awakening and must count in the unit working. PMID- 2099639 TI - [Activity in an emergency care unit: experience of a patient care team]. AB - An emergency and intensive care medical team (physicians, specialised nurses in anesthesia, paramedics) works in a mobile intensive care unit and in a Emergency room. The functions are to provide intensive care, to validate the pre-hospital diagnosis and also to prepare the optimal hospital admission. This organisation realize a "short route" to emergency hospitalisation. A questionnaire to this medical team enquired for their appreciation of the activity, for their implication and feeling, individual and collective, of death's experiences, of works organisation, and of requirements. Mainly, it appears that, with high level of education and various qualification, occupational stress and negative impact on patient care are not described. Further studies are needed to verify. PMID- 2099640 TI - [Stress of nurses]. AB - Since 1989, as supervising nurse, I have been teaching the Surgical Intensive Care team, at the Cantonal University Hospital of Geneva, about the concept of stress and adaptation. An assessment of the lectures has confirmed, beyond field observation, the necessity of this course, the development of the representation of stress among the nursing staff. As a result of the lectures, there have been changes in the organisation of the work in and around the ward (visiting hours, noise, colours of the rooms...), the interpersonal relationships, and in the psychological care of patients (transplants for example). This approach, is based on the idea of D. Chalvin: "The human person is a systematic whole: change the faintest element of his life, or even a quite common behaviour, and it will have most significant consequences on the entire physiological, emotional and mental system". PMID- 2099641 TI - [Consequences on the nursing team of the information of spinal cord injured patients]. AB - For spine-wounded people, an early information about lesions forecast is as necessary as difficult. At the beginning, patients have'nt still realized their state seriousness, and diagnosis stays uncertain. This retrospective work tries to explore how early information is remembered and the consequences about hospital experience, in intensive care unit and in rehabilitation. It shows that early information does'nt modify this experience, but that relations between nurses and patients become better. PMID- 2099642 TI - [Approach of relations to trauma patients in intensive care units]. AB - Because of medical sciences and techniques progresses, Intensive Care Units receive more and more difficult patients. Treatment and care have to respect people human dignity. Person contains body and mind, which are inseparable, as relation and care are. For us, nurses, patients global care have to harmonize technical quality of care and human dimension. PMID- 2099643 TI - [Intensive care ... and after?]. AB - The relations between reanimation's and reeducation's sets are very important. Reanimation's set prepare brain or spinal injured patients to go to the reeducation unit. Aims of reeducation open on quality of life and rehabilitation. PMID- 2099644 TI - [Sleep and psychological disorders in intensive care units]. AB - The evaluation of sleeping and psychical disorders for 24 patients hospitalized during at least 5 days in an intensive care unit was realized through a semi guiding talk with a psychiatrist. All patients were faced to a very disordered sleep and a high number of psychopathological phenomenons: amnesia, disorientation, hallucinations, anxiety, depression. Different factors are concerned in the genesis of those troubles. Some means could prevent it. PMID- 2099645 TI - [Experience of intensive care by medical and nursing staff in transplantation units]. AB - Findings of this paper are responses from more than eighty paramedic staff members or transplantation departments (multi-organs, adults-children) in formation. It concerns three points: specific intensive care for corpses whose organs are to be extracted (teams/relatives); staff in operating rooms where extractions are carried out taking into account cultural anthropology (rituals, ethics, legal aspects); intensive care for new grafts with experimental protocols (children, mucoviscidosis, heart-lungs, small intestine). Two perspectives are set forth successively on the basis of psychoanalysis and anthropology. The scope of closeness and remoteness is a key means to approach the problems inherent in grafts, parallel to the immunologic principle. The extraction of organs causes symbolic and cultural given to appear, leading to the elaboration of fantasies isclosure of archaisms and its fears. So, the positive dynamics of grafts requires a structuring cultural process to preserve their success and intensification. PMID- 2099646 TI - [A team seen by a nurse]. AB - In the initial phase, nurses perceive the person in a coma only as a physical body. Because his feelings and his intelligence are deeply hidden, great is the temptation to see him only as a body. Only when the family is allowed to play its role with the patient, will he be treated with greater care. Nurses have to listen to the family giving informations concerning the patient. The family alone will be able to show how to establish a normal and personalized relationship with the patient. He will then no longer be a passive subject upon which technicians act, but a human being to whom everyone shows respect in every daily dealing. This more human way to care about patients means that nurses are ready to question to some extent their own behaviour. It is indeed a matter of answering personal needs rather than imposing inappropriate totalitarian solutions prepared once for all, for everybody. We all share some responsibility in the quality of the life to come of these patients. PMID- 2099647 TI - [Team and team work]. AB - The coordinator draws conclusions on the symposium day devoted to the teams. After defining "team" he gives several thoughts on the team's work its advantages and its difficulties. During this day the teams talked about their questions and their certainties in the various fields of their work. They also discussed their hard ships and their need of psychological support which the hospital departments do not have the means to satisfy. PMID- 2099648 TI - [Ethics in daily practice of anesthesiology]. AB - Bioethics always has been a great part of medicine, particularly actually in anaesthesiology. From either neonatal distress resuscitation of polymalformated babies or negative vital prognostic babies enduring numerous anaesthesia, to euthanasia for condemned and often suffering patients, there are numerous medical situations in anaesthesiology needing ethical thinking. The circumstances are, in plus, very particular: emergency tense situations, triage during disaster medicine, fundamental decisions concerning personality of unconscious patients. Material needings in such medicine practice, costly monitoring and curative have to be underlined. Then, what a singular relation! The patient confinding the anaesthetist all his vital functions without knowing him. PMID- 2099649 TI - [Dilemma of equity in resource allocation]. AB - The increasing complexity of health care systems in Europe, the financial limits of the public sector one hand, and a political consensus in favour of equal accessibility to services on the other, are at the origin of a widening gap between "individual" ethics (i.e. of health care professionals) and societal ethics. An additional conflict is that between equal accessibility and operational and distributive efficiency. PMID- 2099650 TI - [Between therapeutic life support care and passive euthanasia: objective factors of intensive care in aged patients]. AB - High medical environment in our society is related to an increase of intensive care in old patients. This situation could be looked unappropriate trying to survive people who are finishing their life. An appropriate medical evaluation and management is thus necessary in order to quantifie as fairly as possible both prognosis and specific risk. Factors at the source of mortality in elderly patients are multiple and additive. However two classes of risk can be distinguished. On the one hand some of the risk factors are intrinsic depending on the patient (i.e., neurologic impairement, age, severity of acute illness, previous health status). On the other hand some of the risk are extrinsic related to medical environment (i.e. length of stay in intensive care units, care quality...). This latter risks are improveable and thus are important to be pinpointed. Time is also powerful to assess the best prediction of outcome in old patient. Unlikely mortality rate in elderly is twofold higher (about 35%) as compared as young patients. Evaluation of intensive care unit outcome on 6 months survival make this rate worse as 10% to 20% secondary died. However most of the published studies show that duration in intensive care is similar undepending of age and outcome of the patient. It is also noted that quality of live after intensive care is the same in young or old patient. It is concluded that individual's and society's views concerning cost and effectiveness of intensive care in old patient do not always coincide with objective results. If medical motivation has to be preserved, specific care strategy remained to be established. PMID- 2099651 TI - [On the management of aged patients in intensive and emergency care services]. AB - The management of the elderly patients by the emergency medical service and in the intensive care unit refers to the human and professional experience of the medical team. The treatment of this kind of patients lays down a rule of conduct with the point of view of the economical and moral aspect. PMID- 2099652 TI - [Severe suicides: short- and long-term outcome. Assessment of their quality of life]. AB - From January 1977 to December 1982, 160 patients (10 to 55 years old) were admitted in a traumatic Intensive Care Unit after serious attempted suicides. Hospital mortality rate was about 34%. A questionnaire was sent to alive patients in 1983 (median delay between attempted suicide and questionnaire: 3.5 years); 68 were alive in 1983, 46 answered to questionnaire, 3 were died (two according to a new suicide); 32 could not be found; 85% of contacted patients answered (they were comparable in age, sex and means used in their suicide attempts, to the others). One patient about two must be rehospitalised one or more times. One patient about two must be always take drugs; 85% worked. Over 50% of the patients considered they had returned to their former way of life but 50% presented increased difficulty to work, and 25% said that they had no sequelae. Any of these 46 patients had made an other attempt suicide. PMID- 2099654 TI - [Ethic problems caused by the information of families of organ donors]. AB - Before organ harvesting, previous information of the donor's family is mandatory in France. However information's content and consequences are not specified and may vary widely between hospitals. In some institutions, relatives are only informed of harvesting intent; in others, some teams require family's authorization before harvesting. To make easier and more efficient this information some improvements are suggested. PMID- 2099653 TI - [Organ procurement in pediatrics. General and ethic aspects]. AB - The progress in organ transplantation is leading an increase in the demand for organs. Any non-harvested organs from a dead child mean at least a delay or even the loss of hope for life. All brain dead children do not undergo organ harvesting because there are still obstacles. The definition of brain death must be clear and include the destruction of all the brain system. Intensive care units must be motivated by improved contacts with transplantation teams. The number of parents who refuse could decrease with better public information, good contacts with medical teams and the quality of discussion with parents when a child dies. Energy should be concentrated on improving the collective consciousness about this new aspect of medicine. PMID- 2099655 TI - [Experience of health personnel at an organ procurement center]. AB - Organs' procurement oblige to take care of a great number of brain death patients. This study concerns the psychological influence of such a situation on teams, nurses and physicians of this specific activity of harvesting. It took place in three organs' procurement intensive care units and interested sixty three men and women. These teams reveal the difficulty to live "the brain death", according to brain death patients themselves and their families, but also to transplantation: to work on brain death patients for the life of other patients. So it seem necessary to give a place at a psychologist in this specific intensive care units not for the patients, they are dead, but for the teams. PMID- 2099656 TI - [Round table: ethics, right to life and quality of life]. PMID- 2099657 TI - [Stress and kneipptherapy]. PMID- 2099658 TI - [Genetic probes and their application to the diagnosis of hepatitis B]. PMID- 2099659 TI - [In the memory of Esq. Jose Botella Llusia]. PMID- 2099660 TI - [The scientific work of Dr. Lorente de No]. PMID- 2099661 TI - [Eversion-resection with stapler in cancer of the rectum. Original technique for preserving the sphincter in extreme cases]. PMID- 2099662 TI - [Cancer of the male breast. Report of 20 studied cases]. PMID- 2099663 TI - [Yesterday's, today's and tomorrow's tuberculosis]. PMID- 2099664 TI - [Idiopathic diabetic syndrome: etiopathogenic perspective of its varieties]. PMID- 2099666 TI - [Molecular analysis of cerebral tumors]. PMID- 2099665 TI - [Epistemology of the cancer process]. PMID- 2099667 TI - High ejaculate volume: a distinct entity? AB - In this study clinical, andrological and endocrinological data of a group of 101 patients with ejaculate volume of at least 8.0 ml are compared with data of 100 consecutive patients attending our infertility clinic. Within both groups correlations between different parameters are observed. Between both groups a significant difference in total sperm output is noted suggesting a 'dilution oligozoospermia' in the high ejaculate volume group. We suggest that, in order to avoid a falsely unfavourable fertility prognosis for those patients, total sperm output should be considered rather than sperm density. From the point of view of nomenclature, the term 'relative oligozoospermia' seems justified in cases with very high ejaculate volumes. PMID- 2099668 TI - Seminal lead and copper in fertile and infertile men. AB - Lead and copper concentrations were determined by atomic absorption spectroscopy in semen from 18 fertile and 172 infertile men. Significant correlations between copper concentrations in semen and sperm concentration (r = 0.32, P less than 0.001), percentage progressive motility (r = 0.23, P less than 0.005) and normal morphology (r = 0.22, P less than 0.005) were observed, while no such correlation existed for lead. However, semen copper concentrations of infertile men (194.99 +/- 5.70 micrograms l-1) and fertile men (183.39 +/- 14.37 micrograms l-1) did not differ significantly. Mean lead concentration in semen of fertile men was 11.18 +/- 0.62 micrograms l-1 and significantly higher than lead concentration in semen of fertile men (5.61 +/- 0.53 micrograms l-1, P less than 0.006). Reinvestigation of 18 infertile men after 2 years showed a significant drop of lead concentrations in semen from 17.31 +/- 1.41 to 6.94 +/- 1.32 micrograms l-1 (P less than 0.0002), which might be related to the decreasing use of leaded petrol in the Federal Republic of Germany. PMID- 2099669 TI - Effect of tamoxifen and kallikrein on sperm parameters including hypoosmotic swelling test in subfertile males. A retrospective analysis. AB - 151 subfertile men presenting OAT-syndrome were investigated in respect of an improvement of sperm parameters under therapy with tamoxifen, kallikrein and combined treatment of both drugs. After therapy with 30 mg tamoxifen per day (75 patients), a significant elevation of density and swelling test was seen. Medication with 600 IE kallikrein per day (36 patients) revealed only a slight improvement of motility. Also combined treatment of 30 mg tamoxifen with 600 IE kallikrein per day produced only an elevation of motility without any significant change of other sperm parameters. PMID- 2099670 TI - Hypogonadism of male prolactinomas: relation to pulsatile secretion of LH. AB - In order to investigate whether a hypothalamic disorder cause hypogonadism in male prolactinomas, LH pulsatile secretion was studied in 13 male patients. Serum PRL levels ranged from 186 to 45,000 ng ml-1 before treatment, and all the tumors were macroadenomas. Reduced LH secretion was revealed in 5 of 13 patients, and FSH was reduced in 1 of 13. Serum testosterone (T) levels were lower than the normal limit in all the patients. HCG tests in 3 patients showed good responses, but the peak values of T were lower than those of normal men. LH pulsatilities were examined in 5 hyperprolactinemic patients before treatment, in 4 hyperprolactinemic patients after operation, and in 8 normoprolactinemic patients after operation and/or bromocriptine treatment. There was no significant difference of the mean LH values, the frequencies of LH pulses, and amplitudes among the hyperprolactinemic patients before operation (n = 5), the normoprolactinemic patients after operation (n = 8), and normal men (n = 7). From these results, it was evident that the hypothalamus and pituitary function of male prolactinomas were well preserved, in spite of higher serum PRL levels and larger tumor size than those reported in females. It is suggested that the main cause of hypogonadism in these patients is due to testicular dysfunction resulting from excessive serum PRL. PMID- 2099671 TI - Clinical study of varicocele by sequential scrotal scintigraphy. AB - Sequential scrotal scintigraphy was used to study testicular blood flow in 122 patients with clinically diagnosed varicocele. The sensitivity of scrotal scintigraphy was 91.7% on the whole sequential images. The late-phase image was superior in sensitivity to that of the early-phase images. The difference in time between the arrival of radioactivity in the iliac artery and in the pampiniform plexus grew shorter with increasing grade of varicocele. Time-activity curves were classified into four patterns. One type (Type 3), which was more frequently observed in grade II and grade III varicocele than grade I varicocele, showed a decreased arterial perfusion of the left side lesion. It is concluded that scintigraphic analysis using both sequential images and time-activity curves is not only highly representative of the grade of clinically palpable varicocele, but also provides a better understanding of local hemodynamics in the scrotum. PMID- 2099672 TI - The diagnostic value of seminal adenosine triphosphate (ATP) in an in vitro fertilization (IVF) program. AB - The level of adenosine triphosphate (ATP) was quantitated in semen samples used for in vitro fertilization of human oocytes. Seminal ATP level correlated with the concentration and percentage motility of spermatozoa but not with the in vitro fertilization rate of human oocytes. Seminal ATP measurement appears to have little diagnostic value in predicting the fertilizing capacity of spermatozoa as evaluated by the multivariate stepwise discriminant analysis. PMID- 2099673 TI - Comparison of the effects on penetration capacity of human spermatozoa between using Ham's F-10 medium and a medium based on the composition of human tubal fluid. AB - The penetration ability of human spermatozoa on zona-free hamster ovum when using Ham's F-10 (HF-10) medium was compared with that when using a medium based on the composition of human tubal fluid. Forty semen specimens were each divided into two aliquots; one aliquot was washed with and incubated in HF-10 medium and the other in HTF medium. The penetration rate of sperm with motility between 30 to 60 percent was significantly increased when HTF medium was used (67.9 +/- 6.9%) compared with the rate when HF-10 medium was used (49.2 +/- 7.3%) (P less than 0.05). This study shows that the ZFHO penetration ability of human spermatozoa with poor motility can be improved by using HTF medium as compared with the use of HF-10 medium. PMID- 2099674 TI - Removal of sperm-coat from human spermatozoa by interaction with cervical mucus or a capacitating medium. AB - Human spermatozoa were labelled with cationized ferritin and their interaction with cervical mucus or a capacitating medium enriched with 3% bovine serum albumin (BSA) was investigated by transmission electron microscopy. It was found that the sperm-coat was removed from the surface of spermatozoa after incubation in the BSA-enriched capacitating medium, as well as after crossing a column filled with cervical mucus. These results suggest that both media have a quantitatively similar action in removing the sperm-coat. PMID- 2099675 TI - Anomalous distribution of nuclear basic proteins in round-headed human spermatozoa. AB - An electrophoretic analysis of nuclear proteins has been carried out in normal and in round-headed human spermatozoa. Results revealed an anomalous distribution of nuclear basic proteins in round-headed spermatozoa. They contained more histones and especially more intermediate proteins and less protamines than normal spermatozoa. PMID- 2099676 TI - Electrophoresis of NADH-dependent oxidoreductase (diaphorase) in boar spermatozoa. AB - Two forms of NADH-dependent oxidoreductase (diaphorase [EC.1.6.99.-]) are established in boar spermatozoa. The first form is typical for soluble proteins with a varying electrophoretic profile, while the other form for sedimental proteins with a specific, slowly-moving fraction, which is not common for the soluble form. The two enzyme forms have a close isoelectric point (pI5.5-6.0) and they can not be inhibited by dicumarol 10(-5) mol l-1 and FAD 10(-4) mol l-1. The molecular mass of the soluble form of the enzyme is 28, 37, 46 and 67 kD, while of the sedimental form it is 220, 250 and 260 kD, respectively. PMID- 2099677 TI - Multinucleate epithelial cells in the ductuli efferentes of human epididymis. AB - The histological and ultrastructural study of the ductuli efferentes in epididymides from 40 adult men revealed the occurrence of multinucleate epithelial cells in all specimens. These cells appeared in the luminal protrusions of epithelial folds and correspond to either principal or ciliated cells. The ultrastructure of their cytoplasm did not differ from that of their respective mononucleate cells. Multinucleate cells contained 3-20 closely juxtaposed nuclei, thus appearing much more irregularly outlined than those of the mononucleate epithelial cells. Multinucleation four times more frequent in the principal cells than in the ciliated cells. The number of multinucleate cells increased progressively from the age of 60 years onwards. The average number of nuclei per cell increased in the fourth decade of life, was maintained up to the eighth decade, and then increased again. PMID- 2099678 TI - Ferritin: another pregnancy-specific protein in human seminal plasma and amniotic fluid, as estimated by six methods. AB - Large quantities of ferritin were found in both seminal plasma and amniotic fluid, but there was a wide spread of results for each of six new non-radioactive monoclonal assays designed to give the same results for ferritin in blood serum. Correlation of values between the various assays was also poor, but after the exclusion of outliers it was possible to calculate approximate ratios for the concentrations. For seminal plasma, the Amersham 'Amerlite' luminescence immunoassay gave the lowest concentrations at 81 +/- 56 ng ml-1 WHO 80/602 (mean +/- SD, n = 43). Relative to this value as 100%, the other assays gave:Flow 'Monoscan' colorimetric IEMA = 161%; Pharmacia-LKB 'DELFIA' fluoroimmunoassay = 174%, Walker 'Synelisa' colorimetric ELISA = 182%; Abbott 'IMx' MEIA = 207%, while the results from the Ramco colorimetric ELISA were much higher and not parallel to the other assays. For amniotic fluid, the Amersham 'Amerlite' LIA gave 127 +/- 95 ng ml-1 (n = 38), taken as 100%, and the ratios for the other assays were:Abbott also approximately 100% but with a wide spread; Walker 43%, Pharmacia-LKB 22% and Ramco 148%. The Flow assay produced 15 zero values from 38 samples, and values were also very low in another 17 samples, so that no comparison with the other assays was possible. An attempt was made to determine the proportion of the different types of isoferritins being estimated. The Pharmacia-LKB assay estimated 90% of the theoretical concentration for pure liver ferritin, 42% of that from the placenta, 26% of that from the heart and 13% of that from the spleen. The other assays gave different proportions. PMID- 2099679 TI - [Theresa Kindler poikiloderma in the adult]. PMID- 2099680 TI - [Restrictive or constrictive skin disease: a new lethal genodermatosis]. PMID- 2099681 TI - [Eruptive vellus hair cysts and steatocytoma multiplex in a family]. PMID- 2099682 TI - [Acanthosis nigricans--hyperinsulinism: Seip-Lawrence syndrome]. PMID- 2099683 TI - [Poikiloderma of Rothmund's type]. PMID- 2099684 TI - [Congenital cutaneous metastasis of neuroblastoma]. PMID- 2099685 TI - [Cutaneosystemic congenital mastocytosis]. PMID- 2099686 TI - [Severe pseudotumoral panniculitis in the child: cytophagic histiocytic panniculitis? Favorable outcome with chemotherapy]. PMID- 2099687 TI - [Artificial tanning and extensive burns]. PMID- 2099688 TI - ["Blueberry muffin baby": neonatal extramedullary hematopoiesis? Involutive congenital monoblastic leukemia? Or involutive congenital histiocytosis?]. PMID- 2099689 TI - [Acquired epidermolysis bullosa in children. Report of a case]. PMID- 2099691 TI - [Tuberous cephalic hemangioma with fatal outcome; inefficacy of treatment with alpha interferon]. PMID- 2099690 TI - [Pemphigus in children]. PMID- 2099692 TI - [Generalized Marfanoid congenital cutis laxa with lethal outcome: type V]. PMID- 2099693 TI - [Acute pityriasis rubra pilaris in children. Treatment with etretinate (Tigason)]. PMID- 2099694 TI - [Buccal ulcers disclosing Wegener's disease. Therapeutic value of cyclosporin]. PMID- 2099695 TI - [Fibroblastic rheumatism]. PMID- 2099697 TI - [Cutaneous manifestations of zinc deficiency in Crohn disease]. PMID- 2099696 TI - [Fibroblastic rheumatism]. PMID- 2099698 TI - [Necrotic ulcer patch mimicking factitious panniculitis disclosing systemic lupus erythematosus]. PMID- 2099699 TI - [Generalized post-inflammatory cutis laxa associated with lupic panniculitis]. PMID- 2099700 TI - [Cutaneous manifestations of oxalosis caused by primary hyperoxaliuria]. PMID- 2099701 TI - [Rheumatoid neutrophilic dermatosis]. PMID- 2099702 TI - [Green skin patches disclosing acute pancreatitis]. PMID- 2099703 TI - [Ulcers of the lower limbs and achromic patches disclosing cutaneo-systemic granulomatous vasculitis]. PMID- 2099704 TI - [Leg ulcer disclosing systemic lupus erythematosus with circulating anticoagulant]. PMID- 2099705 TI - [Trichosporon beigelii infection in immunodeficient patients]. PMID- 2099706 TI - [Sweet's syndrome and Yersinia enterocolitica infection]. PMID- 2099707 TI - [Disseminated herpes triggered by isotretinoin in an atopic patient]. PMID- 2099708 TI - [Primary infection by human immunodeficiency virus]. PMID- 2099709 TI - [Unilateral basal cell epitheliomatosis]. PMID- 2099710 TI - [Embryonal botryoid rhabdomyosarcoma. A clinical, histologic and immunohistochemical study of a case]. PMID- 2099711 TI - [Epithelioid sarcoma mimicking melanoma of the foot]. PMID- 2099712 TI - [Congenital monoblastic leukemia and self-healing papulonodular cutaneous lesions]. PMID- 2099713 TI - [Papulovesicular eruption of the face in chronic lymphoid leukemia]. PMID- 2099716 TI - [Erythema annulare centrifugum and Hodgkin's disease]. PMID- 2099714 TI - [Non epidermotropic T lymphoma preceded for several years by hypereosinophilic syndrome]. PMID- 2099715 TI - [Angiocentric lymphoma in Behcet's disease]. PMID- 2099717 TI - [Post-herpetic pseudolymphoma in chronic lymphoid leukemia]. PMID- 2099718 TI - [Hydrostatic bullae]. PMID- 2099719 TI - [Linear IgA drug-induced dermatosis. Report of 3 cases]. PMID- 2099720 TI - [Association of pemphigus and Lyell's syndrome]. PMID- 2099722 TI - [Lassueur-Graham-Little syndrome. 2 cases]. PMID- 2099721 TI - [Cutaneous necrosis of the livedoid Nicolau's dermatitis type]. PMID- 2099723 TI - [Peyrassu's moniliform and macular amyloidosis]. PMID- 2099724 TI - [Acquired disseminated elastolysis of the mid dermis]. PMID- 2099725 TI - Adult embryonal rhabdomyosarcoma of the vagina complicating pregnancy: a case report and review of the literature. AB - Embryonal rhabdomyosarcoma of the vagina in adults per se is uncommon and pregnancy complicated by such tumors is extremely rare. We wish to report one case of vaginal embryonal rhabdomyosarcoma, diagnosed at the age of 23 years who was carrying at the time of initial presentation. The problem of management of rhabdomyosarcoma in adults, particularly when they are associated with pregnancy is discussed. We advocate the use of multiagent chemotherapy and pelvic radiotherapy in its overall management. PMID- 2099726 TI - Macroscopic tuboplasty: reversal of female sterilization. AB - Data is presented regarding 57 women who underwent reversal of sterilization procedure. In the majority (90%), the reason for request for reversal of procedure was loss of male child or more than one child. Thirteen subjects never came back for follow-up. Out of 39 subjects in whom follow-up is available for more than 3 months, in 35 (90%) the tubes are patent. There were 25 pregnancies in 21 subjects and incidence of viable pregnancy was 88% with only ectopic pregnancy (4%). In these 35 cases whose tubes were found to be patent post tuboplasty, 18 had laparoscopic ring application, 16 had abdominal tubal ligation and one had undergone vaginal tubal ligation. Thirteen subjects (62%) conceived within 6 months after reversal. In this series, no loupe or operating microscope was used. PMID- 2099727 TI - Comparative study of combination chemotherapy of ovarian cancer: cyclophosphamide, adriamycin and cisplatin versus 5-fluorouracil, cyclophosphamide and mitomycin C. AB - CAP, a multiple-drug combination therapy using cyclophosphamide (750 mg/m2), adriamycin (20-30 mg/m2) and cisplatin (50-75 mg/m2), was applied to 69 cases of epithelial ovarian cancer. The results of this therapy were compared with those of FAM (involving 5-fluorouracil, cyclophosphamide and mitomycin C) in 47 cases of the same cancer, retrospectively. The 5-year survival rate was 61.6% for cases treated with CAP and 56.3% for cases treated with FAM. All 9 patients at stage Ia treated with CAP are free of disease, however, 3 patients out of 13 at stage Ia treated with FAM experienced a recurrence of the disease and died. In stage III and IV cases with detectable lesions, a response was observed in 61.3% (19/31) treated with CAP and in 10.5% (2/19) treated with FAM. PMID- 2099728 TI - Silastic cup vacuum extractor or forceps: a comparative study. AB - A retrospective analysis over a 2-year period was carried out to compare the limitations in the use of the Silastic Cup vacuum extractor and forceps as the preferred instrument for operative vaginal delivery. Whilst the use of the vacuum extractor was associated with less maternal morbidity (54.9% episiotomy rate; 20.9% nil analgesia) and comparable neonatal problems, an increased failure rate (6.5%) was demonstrated in comparison to forceps delivery (0.7% failed vaginal delivery rate). A comparison of their use for rotational vaginal delivery failed to reveal any significant difference in maternal or neonatal outcome apart from an increased failure rate (30%) to complete vaginal delivery after application of the vacuum extractor. It is concluded that the vacuum extractor is a comparable instrument for midcavity or lift-out instrumental delivery but Kielland's forceps may still be a more appropriate instrument for rotational vaginal delivery. PMID- 2099729 TI - The obstetric management in very-low-birth weight infants. AB - Eighty-three very-low-birth weight (VLBW) infants weighing between 500 g and 1,500 g were studied. The neonatal morbidity and mortality were 86.7% and 18.1%, respectively. Sixty-six point seven percent (8/12) of the infants weighing under 1,000 g suffered from a periventricular-intraventricular or intracranial hemorrhage (PVH/IVH) and their mortality rate was 50%. The incidence of PVH/IVH was 52.1%, and the mortality rate was 12.7% when the birth weight was between 1,000 g and 1,500 g. Forty-nine percent of the PVH/IVH took place on the first day of neonatal life, and 93% developed within 5 days after delivery. Cesarean section neither reduced the incidence of PVH/IVH nor increased the survival rate whether in cephalic or breech presentation. The incidence of PVH/IVH was not affected by type of presentation or the interval between the rupture of membranes and the delivery. Respiratory distress syndrome (RDS) and the requiring of a ventilator for ventilation significantly increased the incidence of PVH/IVH, while a low Apgar score (less than 3) at 5 minutes did not. PMID- 2099730 TI - Maternal mortality: a report from a university hospital in Ankara. AB - Maternal mortality was found to be 140 deaths per 100,000 live births in Hacettepe University Hospital. Infection, hemorrhage and cardiac disease were still the leading causes of maternal deaths. It is possible to reduce the maternal mortality due to these largely preventable causes if standards of care and treatment are raised to a higher level throughout the country. PMID- 2099732 TI - Mature cystic teratoma of the uterine cervix. AB - A rare case of extragonadal teratoma which occurred primarily in the uterus is described. The tumor developed in the uterine cervix to form a polypoid appearance, and consisted of ectodermal, mesodermal and endodermal derivatives. This is the 14th such tumor to be recorded in world literature. A review of the literature and its possible histogenesis are briefly described. PMID- 2099731 TI - Is mucaine an appropriate medication for the relief of heartburn during pregnancy? AB - A double blind comparative study comparing Mucaine, Mucaine without oxethazaine, and placebo was carried out with 50 patients with symptoms of heartburn during late pregnancy. We found that the 2 active treatments were more effective than placebo for the relief of heartburn, but there was no statistically significant difference between groups for the relief of nausea and regurgitation. There was a significant difference in the percentage of days of use of each medication, with the placebo being used least frequently. Although not statistically significant, for the 3 measures for which placebo differed from the active treatments, patients showed a better response to mucaine. This suggests that the addition of oxethazaine may be of benefit. The lack of statistical significance may be due to the relatively small number of cases, and the findings are promising. No side effects were recorded for any treatment. PMID- 2099733 TI - Immunohistochemical localization of CA130 in fetal tissues, and in normal and neoplastic tissues of the female genital tract. AB - A murine monoclonal antibody, 130-22, produced against a human lung adenocarcinoma cell line (PC-9) has been suggested as recognizing an antigenic determinant (CA130) which is different from an epitope recognized by OC125 on CA125 glycoprotein molecules. The immunohistochemical reactivity with the 130-22 antibody (anti-CA130) was examined in human fetal tissues, and normal and neoplastic tissues of female genital tracts, and compared to those using OC125. Among the fetal tissues, the amnion and the cells of coelomic epithelium and mullerian-derived epithelia reacted with anti-CA130. In normal adult tissues, cervical and endometrial gland cells, tubal epithelial cells, and ovarian surface cells reacted with anti-CA130. In addition, predecidual cells in the late secretory endometrium and decidual cells during gestation were positive. Among the neoplastic tissues, tubal and endometrial adenocarcinomas and epithelial ovarian tumors were positive for anti-CA130. There were no differences in the respective specimens between the immunohistochemical localization of anti-CA130 and of OC125. Therefore, anti-CA130 is considered to be useful in the immunohistochemical detection of CA125 glycoprotein molecules as well as OC125. PMID- 2099734 TI - Protein structure, prediction and design. PMID- 2099736 TI - Secondary structure prediction and protein design. AB - For non-homologous proteins, and after cross-validation, the methods reviewed in this article exhibit a probability index (percentage of correctly predicted residues per predicted residues) of 59-65.5% according to the methods employed with a standard deviation of 7% for three conformational states: alpha-helix, beta-strand and coil. These present limitations in the accuracy of prediction are related both to the limited number of known structures and to the effect of long range interactions. The methods based on sequence similarity can improve the accuracy of prediction by expressing the homology of the protein to be predicted explicitly with proteins in the database. Under these circumstances, the probability index can reach 87% with a standard deviation of 6.6%. This property was used for modelling homologous proteins by assisting in amino acid sequence alignments. Examples will be given for the alignment of serine proteinases. PMID- 2099735 TI - An assessment of COMPOSER: a rule-based approach to modelling protein structure. AB - We describe COMPOSER, a computer program for modelling proteins which uses three dimensional structures defined by X-ray analysis together with rules defined by their analysis and comparison. We discuss the modelling of phospholipases and serine proteinases of known structure to assess the errors associated with such models. PMID- 2099738 TI - Identification and design of binding determinants in proteins. AB - Mutagenic analysis are described for probing and designing binding determinants of two different proteins. The first protein is an enzyme, subtilisin, for which structural models were available for the enzyme-substrate complex. The second protein is human growth hormone for which a structural model of its complex with receptor was not available. In both cases, it was possible to identify and engineer binding determinants that lead to large changes in affinity. PMID- 2099737 TI - Restructuring catalysis in the mandelate pathway. AB - Mandelate racemase (MR) is the first enzyme in the bacterial pathway that converts mandelic acid to benzoic acid. The mandelate pathway can utilize either enantiomer of mandelate because this enzyme interconverts them. We have solved the structure of MR at 2.5 A resolution. The enzyme is almost identical in conformation to another bacterial enzyme, muconate lactonizing enzyme (MLE). Both enzymes are TIM-barrel proteins. This result has profound implications for the evolution of enzymic function and the origin of metabolic pathways. It also implies that it should be possible to transform one enzyme into the other by site directed mutagenesis. PMID- 2099739 TI - Antibody-combining sites: prediction and design. AB - For maximum value, a predicted model of an antibody-combining site should have an accuracy approaching that of an X-ray structure (1.6-2.7 A). In addition, the method by which the combining site is modelled should make no demands on the user of a sort that require arbitrary or subjective decisions to be made during the process. We have made substantial progress towards this objective and some recent results are reviewed. In addition, we describe how the modelling protocols developed can aid in the design of novel features within the antibody-combining site. The particular design example reported here suggests an approach for the introduction of metal-binding sites to create metallo-antibodies. This type of modification may be useful in the design of immunobiosensors, the induction of catalytic activity or simply as an alternative to metal chelates in the preparation of antibodies for imaging. PMID- 2099740 TI - Inverting the protein-folding problem. PMID- 2099741 TI - Structural homology in ligand-specific transport proteins. PMID- 2099742 TI - Modelling of binding sites of the nicotinic acetylcholine receptor and their relation to models of the whole receptor. AB - Models for the acetylcholine (ACh)-binding site of the nicotinic acetylcholine receptor (nAChR) are proposed. These models have been developed by using the concept of the ligand-gated ion-channel (LGIC) superfamily of receptors that have evolved from a common ancestor. An initial component of the binding site was identified as a highly conserved 15-residue stretch of primary structure in the N terminal extracellular region of all known LGIC subunits, based on aligned sequence data of LGICs. This subregion, termed the Cys-loop, was modelled as an amphiphilic beta-hairpin and we propose that it forms a major determinant of the binding cleft for agonists. This initial, partial binding-site model has been extended to include residues biochemically identified as spatially adjacent to the binding cleft. A recently developed technique for rapidly scanning the known protein structural database for 'non-homologous similarity' using just sequence information identified the known structure of the enzyme pyrophosphatase (PPase) as a candidate scaffold for the N-terminal domain of the nAChR. This similarity was investigated further using sequence alignments. A framework model of the full N-terminal domain in which the position of the Cys-loop and other binding-site determinants, as well as the main immunogenic region (MIR), have been mapped on to the PPase structure. PMID- 2099743 TI - The expert system approach to predicting protein structure. AB - Prediction of protein structure is an open-ended problem. Since an approach from first principles cannot be taken in reasonable computer time, short-cuts using further data are necessary. Such data include information about the specific protein in question, and information in databases which are about proteins in general. Is it possible to write a general, flexible 'superalgorithm' which would suit most circumstances? If so, it would seem likely to overcome one of the most understated but nonetheless greatest difficulties associated with molecular modelling and computer-aided drug design--reproducibility. To this end, a 'polymorphic programming environment' has been developed which represents both an expert system and a high-level language for theoretical chemists and molecular biologists. This language is GLOBAL (Ball et al., 1990). In a series of earlier studies, and more recently by means of GLOBAL itself, the nature of reproducibility and its rather surprising limits have been explored, and in general the current status and future potential of protein modelling have been examined. PMID- 2099744 TI - Basic design features of the parallel alpha beta barrel, a ubiquitous protein folding motif. AB - Basic design features of the beta-sheet portion in parallel alpha beta barrels in known protein structures are analysed in the context of a model of a regular hyperboloid. A formal description of the relationships between beta-sheet twist, number of strands in the sheet and barrel dimensions is derived, and the underlying physical principles are rationalized. Results suggest that the major constraints on the geometry of the beta-sheet portion of the barrel come from the requirements to have optimal H-bonding interactions between beta-strands and to closely pack amino acid side-chains in the barrel interior so as to exclude bulk water. In addition, we show how the hyperboloid model and the ensuing formalism can serve to derive useful geometric and graphic tools for computer-aided protein design de novo. We then illustrate how these tools are used to determine that the requirement to have a closed regular eight-stranded beta-sheet surface imposes no particular constraints on the geometry (phi, psi angles) of the polypeptide backbone. Understanding the role of the amino acid sequence in determining the observed structures remains a major challenge. Detailed comparisons of known alpha beta-barrel structures (and amino acid sequence) with each other, and with polypeptide fragments from other protein crystal structures, reveal only a limited number of common sequence-structure motifs. These belong to characteristic alpha beta 1 and alpha beta 3 loop families previously described in alpha beta proteins, and occur at least once in nearly all the alpha beta barrel structures examined. PMID- 2099745 TI - Endoscopic sphincterotomy in patients with gallbladder in situ: the influence of periampullary duodenal diverticula. AB - Forty-four elderly patients (mean age, 77.2 years; range, 65 to 95) with acute bile duct obstruction, with gallbladder in situ, underwent endoscopic sphincterotomy without subsequent cholecystectomy during the same hospitalization. Thirty patients had periampullary duodenal diverticula, and 14 had no diverticula. Because periampullary diverticula were associated with biliary and pancreatic complications, possibly as a result of stasis in the diverticula, the clinical course in patients with and without diverticula was compared. Endoscopic sphincterotomy was well tolerated and resulted in a rapid clinical improvement in all patients. There were four complications related to the procedure (pancreatitis, two, and cholangitis, two), all were treated conservatively, and there were no deaths. The clinical outcome was similar in both groups of patients. During a mean follow-up of 25 months (range, 6 to 58), only two patients (one of each group) underwent elective cholecystectomy 2 and 3 months after initial presentation. It is concluded that endoscopic sphincterotomy is a safe and effective alternative to surgery as an initial treatment in elderly patients with choledocholithiasis and gallbladder in situ. Periampullary duodenal diverticulum does not interfere with the favorable results of endoscopic sphincterotomy in patients with gallbladder in situ. PMID- 2099746 TI - Heat treatment of serum and plasma induces false positive results in the antiphospholipid antibody ELISA. AB - We found that levels of antiphospholipid antibodies (aPLA), measured with an ELISA increase if serum or plasma samples are heated. The phenomenon is dependent on duration and degree of heating, optimum levels being reached at 3 h at 56 degrees C. Negative samples become positive after heating. The heating effect is more pronounced for IgG-aPLA than for IgM-aPLA and is not observed for adsDNA, atetanus or lymphocytotoxic antibodies. The presence of serum/plasma components in addition to IgG is essential for the phenomenon to occur. Ultracentrifugation and mixing experiments with isolated IgG did not enable us to explain our observations. Nevertheless, knowledge of this phenomenon is of practical importance. PMID- 2099747 TI - Hairy-cell leukemia and glucose-6-phosphate dehydrogenase deficiency in two brothers. PMID- 2099748 TI - The current status of family medicine geriatric fellowships. AB - A questionnaire was sent to directors of all family medicine-affiliated geriatric fellowship programs to characterize trends and changes since institution of ACGME accreditation of fellowships. The number of fellowships has more than doubled since 1986, but few fellows graduate from these programs. There is currently a surplus of fellowship positions; over half of all programs did not recruit a first-year fellow for the 1989 academic year. In 1986, most family medicine affiliated programs had independent administration. Almost half of the programs are now jointly sponsored with an internal medicine department. These programs are over six times more likely to train internists than family physicians. Although there has been a growth in geriatric training programs over the past three years, the number of family physicians seeking such training remains negligible. PMID- 2099749 TI - Antitachycardia pacing with cardioverter-defibrillator backup for malignant ventricular dysrhythmias. AB - This article provides a summary of the history of antitachydysrhythmic devices and their current application in patients with ventricular dysrhythmias. Future trends are also discussed, followed by a case study illustrating the nursing care required for a patient with a combination antitachycardia pacemaker and automatic implantable cardioverter-defibrillator for slow ventricular tachycardia. The basic principles provided can be incorporated into the teaching plans of patients with antidysrhythmic devices for malignant ventricular dysrhythmias. PMID- 2099750 TI - Epidural analgesia in colonic surgery: results of a randomized prospective study. AB - Colonic surgery patients were studied to measure: the influence of continuous thoracic epidural analgesia (TEA) on a postoperative pain score, the time till onset of defaecation, blood loss, postoperative temperature elevations, rate of bacterial contamination of wounds and urine, and general surgical complications. Group I patients (n = 57) received general anaesthesia and TEA for the operation, followed by continuous TEA (0.25 per cent bupivacaine) for 72 h. Group II patients (n = 59) received general anaesthesia for the operation, followed by systemic analgesia on request. Significant beneficial effects of TEA in group I were demonstrated by lower pain scores in the first 24 h after surgery and earlier defaecation. However, there were fewer temperature elevations in group II. There was no significant difference between the groups in terms of positive bacteriological cultures, blood loss, need for postoperative mechanical ventilation and complications. However, there was a trend toward a higher rate of rectal anastomotic breakdown, increased blood replacement and intensive care therapy, and longer hospitalization in group I. These results do not suggest any significant beneficial therapeutic effect of continuous TEA in colonic surgery compared with a conventional systemic analgesic regimen. In selected patients (i.e. those with severe pain or those prone to develop postoperative ileus) continuous TEA may be beneficial. PMID- 2099752 TI - Microinfusers: stopcock usage for efficiency and asepsis. PMID- 2099751 TI - Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: intergroup study IESS-II. AB - Two hundred fourteen eligible patients with previously untreated, localized Ewing's sarcoma of bone were randomized on IESS-II to receive Adriamycin (ADR; doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, vincristine, and dactinomycin by either a high-dose intermittent method (treatment [trt] 1) or a moderate-dose continuous method (trt 2) similar to the four-drug arm of IESS-I. Patient characteristics (sex, primary site, type of surgery) were stratified at the time of registration; these and other patient characteristics (age, time from symptoms to diagnosis, race) were distributed similarly between treatments. Surgical resection was encouraged, but not mandatory. Local radiation therapy was the same as for IESS-I. The median follow-up time is 5.6 years. The overall outcome was significantly better on trt 1 than on trt 2. At 5 years, the estimated percentages of patients who were disease-free, relapse-free, and surviving were 68%, 73%, and 77% for trt 1 and 48%, 56%, and 63% for trt 2 (P = .02, .03, and .05, respectively). The major reason for treatment failure for both treatment groups was the development of metastatic disease. The lung was the most common site of metastases followed by bone sites. The combined incidence of severe or worse toxicity (67%) was comparable between the treatments; however, severe or worse cardiovascular toxicity was significantly greater on trt 1. Tne only treatment-associated deaths (N = 3) were on trt 1 and were cardiac-related. PMID- 2099753 TI - The value of topical lignocaine gel in pain relief on skin graft donor sites. PMID- 2099754 TI - Outpatient arteriography--a safe and practical proposition? AB - Ninety-five patients, who underwent fine catheter peripheral angiography as outpatients, were followed up and assessed to determine the safety of this procedure. No patients reported any major side effects and in particular no patients experienced a rebleed from the arterial puncture site. This procedure could be safely adopted in any radiology department. PMID- 2099755 TI - MST Continus (morphine) 200 mg: big dose--big money. PMID- 2099756 TI - The biphasic spirogram: a clue to unilateral narrowing of a mainstem bronchus. AB - Two patients with narrowing of a mainstem bronchus each showed two unusual functional features that are likely to be characteristic of this condition. The maximum inspiratory flow-volume curve showed an end inspiratory "tail" and the forced expiratory spirogram had a biphasic shape with normal initial curvature but a "straight line" appearance in later expiration. In one patient relief of the bronchial stenosis by the insertion of a stent restored normal contours to the spirogram and flow-volume curves. PMID- 2099758 TI - Chickenpox in apparently 'immune' hospital workers. PMID- 2099757 TI - Is there a need to reclassify adult rheumatoid arthritis? PMID- 2099759 TI - Occupational and environmental medicine: the internist's role. American College of Physicians. PMID- 2099760 TI - Flying to the rescue: the Northern Region Surf Lifesaving Association Helicopter Rescue Service. AB - The Northern Region Surf Lifesaving Association Helicopter Rescue Service is one of the few aeromedical services in Australia mainly funded and staffed through the voluntary efforts of a local community. Since 1982 the service has flown over 600 missions without accident, rapidly responding to medical emergencies wherever they occur, and moving patients between hospitals whenever rapid and smooth transport has been essential--such as transferring people suffering from spinal and other severe injuries, premature babies, and women in premature or complicated labour. Increasing acceptance of the role of the helicopter amongst doctors and medical authorities has followed this impressive record. This article reviews the special abilities and purposes of the helicopter rescue service and points to its future role in the network of emergency care. PMID- 2099761 TI - Post-marketing surveillance of drugs. The spontaneous reporting scheme: role of the Adverse Drug Reactions Advisory Committee. AB - Post-marketing surveillance of drugs in Australia operates predominantly through the spontaneous reporting of suspected adverse drug reactions (ADRs). Approximately 50% of reports are submitted by hospitals and the rest by individual doctors, pharmacists and dentists. Some 4500 reports ("blue cards") are now reviewed annually by the Adverse Drug Reactions Advisory Committee (ADRAC) and its Secretariat. The register of ADRs has now accumulated more than 65,000 reports. Collations and analyses of data derived from the review process are published to increase awareness by health professionals of drug associated morbidity. Continued educational efforts by professional bodies and regulatory agencies will play a key role in rationalising drug use and reducing drug induced disease. PMID- 2099762 TI - Blood patch in the HIV-positive patient. PMID- 2099763 TI - Consultant oligarchy or workers' cooperative? PMID- 2099764 TI - Bone loss as well as bone formation is a feature of progressive ankylosing spondylitis. PMID- 2099765 TI - Angelman's syndrome in infancy. AB - The authors report an 11-month-old patient with the clinical features of Angelman syndrome and a 15q11 x 2-12 chromosomal deletion, thus demonstrating that the clinical features may be present in infancy and so allow early diagnosis. The features included pronounced postnatal growth failure, delayed dentition and ossification of growth centers. Low amniotic fluid alpha-fetoprotein was noted at 16 weeks of gestation. Head MRI showed only generalized atrophy. Some affected patients have a genetic marker similar to the chromosomal deletion associated with Prader-Willi syndrome. The importance of awareness of the clinical symptoms of Angelman syndrome is discussed. PMID- 2099766 TI - Serological analysis of chicken flocks for antibodies to Salmonella enteritidis. PMID- 2099767 TI - Twins and twinning, dentists and dentistry. AB - Comparisons of physical features within identical (monozygous) and non-identical (dizygous) twin pairs have provided valuable insights into the relative contributions of genetic and environmental influences to observed variability. The special nature of the twinning process itself also provides an opportunity to learn more about early human development, including how body symmetry is determined. The mechanisms of twinning, mortality and morbidity in twins, determination of body symmetry including the phenomenon of mirror-imaging, postnatal growth and development of twins, and zygosity determination are discussed. Twin studies with direct relevance to clinical dentistry are reviewed and illustrated by examples from an ongoing investigation of dentofacial morphology in South Australian twins. PMID- 2099768 TI - Benzodiazepine withdrawal. PMID- 2099769 TI - Informed consent--help or hindrance. PMID- 2099770 TI - Interpretation of dope test results in racehorses. PMID- 2099771 TI - Internal migration of British doctors during training. PMID- 2099772 TI - Cancer in an ileoanal reservoir. PMID- 2099773 TI - Transbronchial lung biopsy. PMID- 2099774 TI - Tobacco-induced diseases in South Africa. PMID- 2099775 TI - The true apical hypertrophic cardiomyopathy. PMID- 2099776 TI - Medical oncology chapter. PMID- 2099777 TI - The heat induced aPL ELISA reactivity is not a false positive phenomenon. PMID- 2099778 TI - Arthrogryposis multiplex congenita with Peter's anomaly. PMID- 2099779 TI - Fractures of the femoral neck: a retrospective and prospective study. PMID- 2099780 TI - Intraocular lens implants in patients with uveitis. PMID- 2099781 TI - Binding of [3H]serotonin to lymphocytes in patients with neuropsychiatric disorders. AB - Based on recent studies of neuroimmune networks, the lymphocyte binding of serotonin neurotransmitter was studied in patients with Alzheimer's disease, idiopathic mental retardation, and autism. The specific binding to lymphocytes of [3H]serotonin, at a single concentration of 100 nM, was significantly reduced in Alzheimer's disease patients as compared to aged controls (group mean of 3.667 +/ 2.301 v 7.506 +/- 1.717 picomoles; p = 0.001), and in children with idiopathic mental retardation as compared to healthy children (group mean of 3.694 +/- 1.627 v 5.792 +/- 1.902 picomoles; p = 0.003). However, autistic children did not differ significantly from the healthy children (group mean of 5.287 +/- 1.987 v 5.792 +/- 1.902 picomoles; p = 0.475). Reduced lymphocyte binding of serotonin may be an indication of breakdown of an unknown neuroimmune pathway relevant to the pathophysiology of Alzheimer's disease and idiopathic mental retardation. PMID- 2099782 TI - Abnormality in cultured oligodendrocytes and Schwann cells isolated from the twitcher mouse. AB - Oligodendrocytes and Schwann cells were isolated from the brain and dorsal root ganglia of the twitcher mouse, a murine model of Krabbe's disease (globoid cell leukodystrophy), and grown in tissue culture. Oligodendrocytes were cultured for up to 22 d in vitro and were immunostained with a galactocerebroside antibody, a specific marker for oligodendrocytes. The control oligodendrocytes developed well branched processes and membrane sheets, whereas the twitcher oligodendrocyte had wirelike processes with no membrane expansion and progressive degeneration. Schwann cells from the twitcher could not extend their processes as long as normal counterparts. The amounts of psychosine in the enriched population of oligodendrocytes and Schwann cells from the twitcher mouse are about 50-fold and 70-fold higher, respectively, than those in the control cells. These data suggest that psychosine may play an important role in the progression of abnormal features of oligodendroglial membrane formation and in the absence of process elongation in Schwann cells in the twitcher mutant. PMID- 2099784 TI - Short- and long-term effects of L-dopa administration on striatal acetylcholinesterase activity. AB - Exogenously applied dopamine may interfere with cholinergic activity in the brain. The aim of the present work was to study the effect of L-dopa administration on acetylcholinesterase (EC 3.1.1.7) activity in rat (Wistar) brain striatum. Short-term administration of a mixture of L-dopa (10 mg/kg) and carbidopa (1 mg/kg) resulted in an increase in dopamine content and a decrease in acetylcholinesterase activity of the tissue. The greatest changes were found 30 min postinjection, and activity returned to near-control values after 2 h. When the drug mixture was injected for a period of 30 d and the animals were killed 24 h after the last injection, a lower dopamine content and higher enzyme activity were seen, compared to control values. It would appear that chronic administration of L-dopa gradually reduced the dopamine-storage capacity of the striatum and that the activity of acetylcholinesterase might be controlled by the levels of dopamine in the brain striatum. PMID- 2099785 TI - Urinary excretion of metabolites of norepinephrine in Tourette's syndrome. AB - Urinary excretion of the norepinephrine metabolites 3-methoxy-4 hydroxyphenylethylene glycol (MHPG) and normetanephrine (NMR) was measured in Tourette's Syndrome (TS) patients and in control subjects matched for age and education. The 24-h excretion (expressed per gram of creatinine) of total MHPG and of free and total (free + conjugated) NME was significantly lower in TS patients than in the normal subjects. PMID- 2099783 TI - Glycosphingolipids in the cerebrospinal fluid of patients with multiple sclerosis. AB - Glycosphingolipids in cerebrospinal fluid (CSF) of individual patients with multiple sclerosis (MS) were analyzed using a glycolipid-overlay technique. The ganglioside composition of CSF of non-MS patients was characterized by an abundance of polysialo species, including GT1b and GQ1b. This pattern is completely different from that of human white or gray matter, in which mono- and disialogangliosides predominate. Increased levels of GM1, either associated with or without increases of other gangliosides, such as GD1a, were observed in 16% of the patients with MS (6 of 37 cases: 1 of 15 progressive progressive stage, 4 of 16 progressive stationary stage, and 1 of 6 relapsing stage). The concentration of GD3 was increased in 23% (3 of 13 cases), whereas 1 of 13 cases (8%) showed a dramatic increase of sulfoglucuronyl paragloboside (SGPG) associated with a high level of GD3. These changes may reflect the cellular changes associated with the known pathological lesions in MS, which are characterized by demyelination, gliosis, and/or remyelination with oligodendrocytic proliferation. PMID- 2099786 TI - CO and particle pollution of indoor air in Beijing and its elemental analysis. AB - Three representative types of houses in Beijing were selected and, in each type, smoking and nonsmoking households were compared, IP, RP, and CO concentrations in the living room and kitchen were monitored during each season, and the level of COHb in the heads of the households were measured. The study showed that indoor air pollution was rather severe, especially during winter, when particulate concentrations markedly exceeded the standard and CO concentration was as high as 47 ppm. Indoor air pollution was closely related to the type of house, particularly to the mode of heating. In houses, of the same type, pollution improved greatly after central heating facilities were installed. Analysis of 30 elements revealed that pollution was typically caused by coal burning, aggravated by dusty wind, but high indoor Pb levels were probably due to the use of LPG for cooking. In our study the effect of cigarette smoking was sometimes masked by the severe indoor pollution. PMID- 2099787 TI - Changes in myelinated nerve fibers and skeletal muscle of rats exposed to high doses of permethrin. AB - Neurological signs and segmental demyelination in a cervical nerve were observed in rats treated orally with permethrin (300 mg/kg/day) for 5 days. Inflammatory and degenerative signals were recorded in the diaphragm muscle. These effects were more intense with the trade grade than with the technical grade product. The possible influence of the percentage of cis:trans isomers on the intensity of the observed effects is discussed. PMID- 2099788 TI - Analysis of the phenotype and the restriction enzyme mapping level of mutations induced by the new mutagen glycidyl methacrylate. AB - Glycidyl methacrylate (GMA) is a recently recognized chemical mutagen. In order to explore the mutagenicity and mutagenic process of GMA, plasmid pBR322 was used for in vitro binding, mutant screening, and restriction enzyme mapping. The binding between GMA and DNA in vitro has been verified by means of a spectrophotometric method. When pBR322 and GMA-bound pBR322 were used to transform Escherichia coli HB101, the following results were obtained: (1) The transformation efficiency of GMA-bound pBR322 was much lower than that of pBR322 alone. (2) GMA-bound pBR322 induced phenotype changes in competent cells (i.e., tetracycline-resistance inactivation or ampicillin-resistance inactivation). There were two mutants of pBR322, ApRTCS and ApSTcR, in the transformants and a deductive mutant ApsTcs in the nontransformants. (3) All of the selected mutants were stable and heritable. (4) When restriction enzyme maps were used to analyze the mutant ApRTcS, four of seven maps were changed, some sites were shifted to other resistant gene regions, for example, sites of Bg/I, EcoRI, HindIII, HincII, etc., and there was a new recognition site for HincII (252). We did not observe any DNA fragment insertion or deletion on any maps. Our results suggest that when GMA is covalently linked to the plasmid DNA, it gives rise to a premutagenic lesion of DNA that is converted in vivo into a point mutation. PMID- 2099789 TI - Enzymatic and ultrastructural studies in a freshwater catfish: impact of methyl parathion. AB - Exposure to a sublethal concentration of methyl parathion (MEP) reduced the activity of cytoplasmic malate dehydrogenase, mitochondrial malate dehydrogenase, and lactate dehydrogenase by 30 to 49% in the liver and the skeletal muscle of the freshwater catfish. Clarias batrachus, after 7 days. The activities then began to recover and reached the control levels on the 28th day of MEP exposure. A complete recovery occurred on the 7th day when MEP was withdrawn from the medium after an exposure for 1 week. The withdrawal-dependent recovery in the activities was inhibited partially or completely by actinomycin D and cycloheximide, suggesting de novo synthesis of the enzymes during the recovery period. A conjoint treatment of MEP and triiodothyronine (T3) restored the activities to control levels, indicating T3 protection against the pesticide toxicity. SDS-PAGE of the cytoplasmic fraction of the liver showed some noticeable changes in the protein pattern after an exposure to MEP. Ultrastructural studies on MEP-treated liver cells showed disappearance of the glycogen granules and appearance of numerous smooth endoplasmic reticulum, lysosomal dense bodies, and swollen mitochondria. These changes in the liver are an indication of hepatic toxicity leading toward necrosis. PMID- 2099791 TI - Removal of lead from aqueous solution by Acinetobacter calcoaceticus. AB - A bacterial strain tolerant to the presence of 400 ppm lead was isolated from digested sewage sludge. The organism was identified as Acinetobacter calcoaceticus var: anitraus (98% confidence). Both viable and formalin inactivated bacterial cells could remove Pb from an aqueous solution. The Pb binding ability of inactivated cells was compared with that of a commercial ion exchange resin. Amberlite IR-120. The metal-binding ability of A. calcoaceticus followed the sequence Pb greater than or equal to Cu greater than or equal to Cr greater than or equal to (Cd, Ni, and Zn) greater than or equal to Co. The ability of the inactivated cells to remove Pb was pH sensitive, and the adsorption process was slightly affected at high temperature (70 degrees C). The adsorption and desorption process worked equally well with A. calcoaceticus embedded in a polyacrylamide gel matrix. PMID- 2099790 TI - Oncogenes, oncogenesis, and oxygen radicals. AB - The role that free radicals in general and oxygen radicals in particular play in carcinogenesis has attracted considerable attention in recent years. The oxygen radicals are undesirable but inevitable products of aerobic metabolism in the normal living cell. The cellular antioxidant defense system maintains an appropriate balance between necessary oxidative events and those that are excessive. When this critical balance cannot be maintained because of the overloading of the cellular redox system, oxygen radicals can induce cell damage. They can influence carcinogenesis by inducing DNA damage from direct oxidation or indirectly from DNA-binding products of lipid peroxidation. Oxygen radicals can induce conformational changes in the plasma membrane by lipid peroxidation and protein degradation, thus influencing membrane-associated cellular activities. They are capable of affecting membrane-bound protein kinases, growth factors and their receptors, and, therefore, signal transduction and oncogene activation. Thus, the oxygen radicals can have a major influence on oncogenes and oncogenesis. PMID- 2099792 TI - Chemical safety as a major challenge for developing countries: role of the International Program on Chemical Safety. AB - Developing countries face a number of unique problems related to the hazards of chemicals. The WHO International Program on Chemical Safety may play a useful role by working jointly with Member Nations and such international organizations as FAO, UNEP, and ILO. PMID- 2099793 TI - Chemical management of forest pest epidemics: a case study. AB - The management of insect epidemics in large tracts of forest is difficult given the climatic conditions encountered, the topography of the forested land, the nature of the forest, the types of chemical and/or biological insecticides registered for use, and the technologies available for insecticide application. Since 1952, the province of New Brunswick, Canada, has been heavily involved in attempting to control an epidemic of the eastern spruce budworm (Choristoneura fumiferana. Clemens) that has ravaged the coniferous softwoods of eastern Canada and the United States. Of the available options, the provincial government chose to develop an aerial spraying program, eventually selecting two chemical insecticides (fenitrothion and aminocarb) and one biological control agent (Bacillus thuringiensis). Concerns about possible impacts on human health led to extensive studies of the toxicology of these insecticides, the technology of aerial spraying, the development of less hazardous formulations, and the quantitation of off-target drift of aerosolized insecticides. These studies culminated in improvements in pesticide application and the establishment of regulations on safety or buffer zones around human habitation for certain types of aircraft applying different formulations of the insecticides. PMID- 2099794 TI - Embryonic stem cells: proliferation and differentiation. PMID- 2099795 TI - Bone cell differentiation: a functionally coupled relationship between expression of cell-growth- and tissue-specific genes. PMID- 2099796 TI - Extracellular factors, signalling pathways and differentiation of adipose precursor cells. PMID- 2099797 TI - Regulation of neural cell survival and differentiation by peptide growth factors. PMID- 2099798 TI - Muscle cell differentiation and alternative splicing. PMID- 2099799 TI - Myogenesis and developmental control genes. PMID- 2099800 TI - Messenger RNA transport and localization. PMID- 2099801 TI - Scanning, internal initiation and the control of the initiation of protein synthesis. PMID- 2099802 TI - The role of poly(A) in the translation and stability of mRNA. PMID- 2099803 TI - Pseudoknots and the control of protein synthesis. PMID- 2099804 TI - Peptidyl-prolyl cis-trans isomerases, cyclophilin, FK506-binding protein, and ninaA: four of a kind. PMID- 2099805 TI - Acylation and prenylation of proteins. PMID- 2099806 TI - Protein glycosylation. PMID- 2099808 TI - Cell differentiation. PMID- 2099807 TI - Subtilisin-like proteinases involved in the activation of proproteins of the eukaryotic secretory pathway. PMID- 2099809 TI - Post-transcriptional processes. PMID- 2099810 TI - Inductive interactions in early amphibian development. PMID- 2099812 TI - Cell lineage in vertebrate development. PMID- 2099811 TI - Pattern formation in vertebrate limbs. PMID- 2099813 TI - Cell-cell interactions in the nematode Caenorhabditis elegans. PMID- 2099814 TI - Early Drosophila development. PMID- 2099815 TI - Transcriptional control and the integration of cell-autonomous and environmental cues during development. PMID- 2099816 TI - [Evaluation of patients with craniocerebral trauma]. PMID- 2099817 TI - [Benign intracranial hypertension and obesity]. AB - The incidence of obesity and excess weight were analyzed in a series of 100 cases of benign intracranial hypertension (BIH) and compared with a control group. The results of hypocaloric diet and lumbar puncture were compared to those obtained with other treatments. Relapses of the disease were analyzed in obese patients who maintained a normal weight after clinical recovery and compared with those who get fat again. A similar analysis was carried out in pregnant women. The frequency of sequelae in obese patients was also determined. A high incidence of obesity was observed only in women aged 20 to 40 years who presented BIH. Hypocaloric diet and lumbar puncture constituted the treatment which exerted a more marked shortening of the clinical course. Relapses of BIH were more frequent in obese patients who did not normalize the body weight and in new pregnant women. Data indicate the relevance of obesity as etiopathogenetic factor in a group of patients with BIH. PMID- 2099818 TI - [Morbidity and mortality in craniocerebral trauma: epidemiologic study in Cantabria]. AB - Morbidity and mortality of the patients with head injury (HI) admitted to our institution during one year were prospectively evaluated. Four hundred and seventy seven fulfilled the inclusion criterial this represents an incidence of HI of 91/100,000/year for our community. Male/female ratio was 2,9/1. Traffic accidents were the most common cause of HI (60%). The clinical evaluation at admission with the Glasgow coma scale classified 88% of HIs as mild and 12% as moderate or severe. Recovery, following the Glasgow outcome scale, was good in 97%. The greater initial severity of HI and the lack of protective measures were respectively associated with a poorer clinical outcome and with a higher incidence of cranial and cerebral lesions. There were eigth hospital deahts, all in the group with severe scores; thus, the mortality rate in this group was 33%. Deaths outside the hospital were 95, i.e., 92% of the overall mortality. Our results confirm the public health relevance of HI, the very high prognostic value of the current evaluation scales and the insufficient use of protective measures in our area. Finally, the high rates or death outside the hospital suggest that emergency medical care outside the hospital is poor. PMID- 2099820 TI - [Stiff man syndrome (Moersch and Woltman syndrome). Description of two cases]. AB - This study reports two female patients with progressive muscular rigidity beginning to the paravertebral and pelvic muscles associated with muscular spasms. The electromyography showed continuous muscular activity originated at the central nervous system. In both cases we observed the complete rigid man syndrome. Complementary explorations including thyroid hormonal study, ceruloplasmin, electroencephalogram, cranial computerized tomography, and magnetic resonance were normal. Auditive evoked potentials evidenced a prolongation of the interlatency III-V, suggesting pathologic involvement of the encephalic trunk. In one patient an artificial reservoir was inserted to instill baclofen into the meningeal space and produced a clinical improvement. The actual status of this rare illness is reviewed. PMID- 2099819 TI - [Cerebral circulation and neurologic diseases related to oxidative stress. Free radicals and antioxidants]. PMID- 2099821 TI - [Idiopathic cerebral gas embolism]. AB - Air embolism to the brain is an accident that may occur in situations that favour the entrance of air into the bloodstream. The clinical diagnosis is sometimes difficult and only the computerized axial tomography may be of invaluable help. We present a rare case of air embolism occurring during sleep in which no apparent causes could be established. This woman had clinical findings of extensive infarction at the right cerebral hemisphere. The axial tomography performed during the first five days showed the presence of air bubbles persisting for three days and areas of infarction and edema during the 3rd-5th day. Magnetic resonance evidenced new areas of infarction in both hemispheres by the 12th day. Application of antiedema therapy was followed by a partial clinical recovery. PMID- 2099822 TI - [Cerebral hemorrhage associated with the use phenylpropanolamine]. AB - Phenylpropanolamine is a sympatheticomimetic agent which is widely used in pharmacologic preparations to treat nasal congestion, and to produce and anorexigenic or stimulant action. In the last years complications affecting the nervous system or the general condition have been reported. There is still controversy with regard to the safety of this pharmacologic agent. In this study we report two cases of parenchymal cerebral hemorrhage secondary to phenylpropanolamine administration. In the second case we observed angiographic findings of a reversible vasculopathy. PMID- 2099823 TI - [Mills' syndrome secondary to hypoplasia of the basilar artery]. PMID- 2099824 TI - [Subacute myopathy as the initial symptom of hyperthyroidism]. PMID- 2099825 TI - [Syringomyelobulbia and bilateral paralysis of vocal cords]. PMID- 2099826 TI - [Magnetic resonance findings in optical neuritis]. PMID- 2099827 TI - Seroepidemiological survey for yellow fever antibodies in domestic animals. AB - A total of 192 out of 300 serum samples from camel, cattle, sheep and goats tested for yellow fever virus antibody by the counterimmunoelectrophoresis were found positive. This test was confirmed by the single radial haemolysis and serum neutralization tests. Twenty-one and 36 sera were positive for specific yellow fever virus antibodies by the single radial haemolysis and serum neutralization tests respectively. The possible role of these animals in the epidemiology of yellow fever is discussed. PMID- 2099828 TI - [35 years of research and study in radiovirology at the Stefan S. Nicolau Institute of Virology]. AB - The report presents researches conducted in the field of radiovirology, these 35 last years, at the Radiovirology Central Laboratory of the Academy of Medical Sciences: ionizing radiation little dose effects on the evolution of virus infections, virus migration through the infected organism and its stocks in different organs, intracellular synthesis of viruses, radioisotope characterization of viral nucleic acids, studies of viral molecular biology, radioimmunologic diagnosis of virus diseases, virus inactivation and sterilization through ionizing radiation, space virology studies within "Intercosmos" research program. PMID- 2099829 TI - [The improvement of a serological screening method in blood transfusion]. AB - The mathematical analysis was done of the opportunity of modifying the serological screening method in view of the reduction to a minimum of the costs. Two factors were considered: dimensions of the pool and specific incidence of the markers in the population. PMID- 2099830 TI - [Acute respiratory infections of viral origin in the children of Algiers, Algeria based on a seroepidemiological study]. AB - 401 double serum samples from 0 to 14 year old children with acute respiratory diseases (ARD) were analysed in view to establish the viral etiology. 198 (49.4%) out of the 401 were positive. The syncytial respiratory virus (SRV) was the most frequent (29.8%) among the positives, followed by the parainfluenzae virus type 3 (24.7), the influenza A virus (23.7%), the parainfluenzae type 1 (8.5%), the influenza B (7%) and the parainfluenza type 2 (2%). Seven samples out of 109 were positive for adenovirus. The SRV infections were very frequent before one year of age and after six. The parainfluenza virus type 3 was found mostly during the second year of life and was different in this from the types 1 and 2 prevalent after the age of six. The SRV is responsible for subglottic ARD (73%), as well as the parainfluenza virus type 3 (68.5%), the influenza virus types A (69%) and B (61.5%). On the contrary, the parainfluenza viruses types 1 (70%) and 2 (67%) attacked especially the upper respiratory tract. Studies were also worked out on the effects of season, sex, antibiotherapy, as well as on the viruses most incriminated in hospitalization. PMID- 2099831 TI - [The virological study of a certified focus of acute respiratory diseases in a half-closed community]. AB - An acute respiratory disease outbreak appeared during February and March 1988 in a half-closed community. Virologic investigations were conducted and an influenza virus type B strain was isolated, antigenically like B/Victoria 2/87. Administration of the anti-influenza vaccine in the fifth day of the outbreak evolution led to considerable reduction of the new cases and to outbreak extinction after 48 hours. PMID- 2099832 TI - Distribution and isolation of four laminin variants; tissue restricted distribution of heterotrimers assembled from five different subunits. AB - The distribution of subunits of the basement membrane proteins laminin and merosin in human and rabbit tissue was studied by immunofluorescence using monoclonal antibodies. The laminin A chain is present in epithelial, endothelial, and smooth muscle basement membranes. Merosin, as defined by its heavy chain M, is present in striated muscle and peripheral nerve. The A subunit colocalizes with at least two B subunits: B2 plus either B1 or the recently discovered B1 homologue S. The M subunit most often colocalizes with B1 and B2. Exceptions include the myotendinous junction, where M colocalizes with S, and the trophoblast basement membrane, where the M subunit colocalizes with S as well as B1. The presence of all five known subunits of the laminin family in placenta allowed isolation of their parent molecules in native form by the use of monoclonal antibodies in affinity chromatography. Four different heterotrimeric proteins could be identified: B1 chain-containing laminin (A-B1-B2), S chain containing laminin (A-S-B2), B1-containing merosin (M-B1-B2), and S-containing merosin (M-S-B2). The data show that the proteins in the laminin family are heterotrimers composed of one heavy and two light chains; that most basement membranes contain predominantly one protein of the laminin family; and that laminin, as defined by the A subunit, has a much more restricted distribution than previously thought. PMID- 2099833 TI - Developmental regulation of calmodulin-dependent adenylate cyclase activity in an insect endocrine gland. AB - The insect prothoracic gland produces ecdysteroids that elicit molting and metamorphosis, and neurohormone stimulation of steroidogenesis by this gland involves both Ca2+ and cyclic adenosine monophosphate second messengers. Prothoracic gland adenylate cyclase exhibits a complex Ca2+/calmodulin (CaM) dependence, a component of which requires an activated Gs alpha for expression. A developmental switch in this system has been identified that correlates with a change in both regulation and function of the gland and involves the loss of sensitivity to extracellular Ca2+ at a time approximately concurrent with the loss of Ca2+/CaM sensitivity by the adenylate cyclase. The extent of cholera toxin activation of gland Gs alpha is lowered before this developmental switch. However, no alterations in Gs alpha levels or mobility are detected, suggesting that Gs alpha interaction with another component in the signaling pathway, perhaps adenylate cyclase itself, produces the apparent Ca2+/CaM dependence and influences the ability of toxin to modify Gs alpha. PMID- 2099835 TI - High-risk groups and preventive measures in breast cancer. PMID- 2099834 TI - Pathology of preinvasive and excellent-prognosis breast cancer. PMID- 2099836 TI - Adjuvant therapy in breast cancer. PMID- 2099837 TI - Biologic aspects, classification, surgery, and radiotherapy of stage III breast cancer. PMID- 2099838 TI - Chemotherapy and hormonal therapy in stage III disease; inflammatory breast cancer. PMID- 2099839 TI - Treatment of metastatic breast cancer. PMID- 2099840 TI - Psychosocial aspects of breast cancer. PMID- 2099841 TI - Alkylating and platinum-based agents. PMID- 2099842 TI - Antitumor antibiotics, epipodophyllotoxins, and vinca alkaloids: clinical developments. PMID- 2099843 TI - Recent clinical experience with tumor necrosis factor and advances in understanding its physiologic function and cellular activities. PMID- 2099844 TI - Problems, controversies, and perspectives on the clinical use of interleukin-2. PMID- 2099845 TI - Monoclonal antibodies and tumor vaccines. PMID- 2099846 TI - Recent advances in AIDS-related Kaposi's sarcoma. PMID- 2099847 TI - AIDS-associated lymphoma. PMID- 2099849 TI - Breast cancer. PMID- 2099848 TI - Miscellaneous cancers associated with HIV infection. PMID- 2099850 TI - Therapeutic modalities. PMID- 2099851 TI - Cancer in AIDS. PMID- 2099852 TI - [Third generation cephalosporins and antibiotic prophylaxis in surgery]. PMID- 2099853 TI - [Bacteremia in the patient with liver cirrhosis. Prospective study of 61 episodes]. AB - We prospectively evaluated 61 episodes of bacteremia in 54 patients with hepatic cirrhosis, representing 9% of the overall number of bacteremic episodes in adult patients seen in our center during the study period. Spontaneous bacteremia represented 46% of all episodes (virtually always in patients with ascites), followed by the urinary origin (30%). Gram negative organisms were isolated in 71% of episodes. 43% of these were hospital-acquired 25% of patients had spontaneous peritonitis. Among other complications of bacteremia there were shock (28%), renal failure (24%), and disseminated intravascular coagulation (6%). The mortality rate due to sepsis was 28%, that due to complications of cirrhosis by itself was 20%, and that of nonrelated diseases was 8%. Shock and renal failure secondary to bacteremia were independent predictors of a poor prognosis. PMID- 2099854 TI - [Candida esophagitis treated with a single dose of fluconazole in patients with HIV: presentation of 11 cases]. AB - We have reviewed the efficacy of the use of fluconazole in patients with definitely proven Candida esophagitis (CE) associated with human immunodeficiency virus (HIV) infection, using a single 400 mg oral dose of fluconazole and evaluating the patient three days afterwards. This drug showed to be effective for the clinical and endoscopic cure in all patients (100%), and with microbiological cure in ten cases. There was no clinical feature of toxicity. The only side effect was an increased alkaline phosphatase and transaminase activity without hyperbilirubinemia, but this finding was not statistically significant (p greater than 0.05). Fluconazole, given in a single 400 mg dose, was absolutely effective to cure esophagitis in AIDS, thus permitting to avoid parenteral amphotericin. PMID- 2099855 TI - [Bacteremia and fungemia in patients with AIDS. Study of 56 episodes]. AB - We report 56 episodes of bacteremia and fungemia in 45 patients (23%) out of overall 193 cases of AIDS. 41% of the isolates were gram-negative bacilli, with a predominance of Salmonella enteritidis (30%), most of them community-acquired. Gram-positive cocci (18 episodes) were hospital-acquired in 61%, with a predominance of Staphylococcus sp (10 cases). Mycobacteria and Cryptococcus neoformans were isolated in 8 patients. 88.8% of our patients with cryptococcosis (8/9) had positive blood cultures. 76% of the episodes (43/56) were community acquired, with a high incidence of primary bacteremias (59%). 48% of the patients were cured, whereas 27% died from causes related with the bacteremia. PMID- 2099856 TI - [Nosocomial bacteremia caused by Serratia marcescens: analysis of 44 cases]. AB - We have evaluated 44 cases of Serratia marcescens bacteremia (SB). Most took place in surgical services (57%) and the ICU (34%). In one occasion, the cases developed as an epidemic outbreak. SB basically developed in patients with underlying diseases (neoplasia in 32%, heart disease in 16%, chronic bronchitis in 14% and miscellaneous in 20%) in whom some invasive procedure had been carried out (98%). The most common complication was septic shock. In 17 cases the infection was polymicrobial. The most common serogroup was 0:5 (41%). 98% of strains were resistant to cephalothin, 78% to ampicillin and 29% to tobramycin. The mortality rate was 39% and the most common cause of death was septic shock. The factors which adversely influenced prognosis were as follows, in order of decreasing importance: leukocytosis, thrombopenia, associated gram-positive infection, age older than 65 years, "non-typable" serogroup, unknown portal of entry, epidemic case and septic shock. PMID- 2099857 TI - [Multicenter study of fluconazole in the treatment of oropharyngeal candidiasis in immunodepressed patients]. AB - We have evaluated the efficacy of fluconazole, 50 mg/day for 2 weeks, to treat oropharyngeal candidiasis in immunologically compromised patients. There were overall 27 patients, 25 of which were HIV+ and 2 had neutropenia. The rate of clinical response at the end of therapy, and one week and one month afterwards were 96%, 76% and 64%, respectively. The microbiological eradication was achieved in 36% of patients. The tolerance of the drug was satisfactory, although in 3 cases features of hepatic toxicity were detected. The convenience, good tolerance and clinical efficacy of fluconazole make it the therapy of choice for oropharyngeal candidiasis in immunologically compromised patients. PMID- 2099859 TI - [Antibody-coated bacteria and quantitative culture in sputum samples from patients with bronchiectasis]. AB - The results of the quantitative culture of sputum samples from patients with bronchiectasis were compared with those obtained in the same samples with the detection of antibody-coated bacteria (ACB), in the acute phase of the disease (group I), after antibiotic therapy (group II), and in the phase of clinical stability (group III). In quantitative cultures at least one potentially pathogen species was isolated, at a concentration of greater than or equal to 10(6) colony forming units/ml in the 7 sputum samples from group I, in 4 of the 5 samples from group II, and in 10 of the 11 samples from group III. The immunofluorescence technique detected ACB in all samples from group I and group II, and in 10 of the 11 from group III. The sample from group III in which ACB were not detected was the same in which potentially pathogen organisms were not detected by culture. PMID- 2099858 TI - [Bacteriological study of bile from the gallbladder and bile ducts of patients surgically treated for biliary pathology]. AB - We have evaluated the results of a bacteriological study of bile in 115 patients undergoing biliary surgery in the Valdivia Hospital (Chile). 35.6% of the positive bile cultures corresponded to patients with acute cholecystitis and only 22.5% to chronic disease. The culture was positive in 56.3% of cases of common bile duct stones and in 86.7% of cholangitis. Most positive bile cultures were monomicrobial, corresponding to patients with chronic cholecystitis. Most isolates were from Enterobacteriaceae, 49% of which corresponding to Escherichia coli. The in vitro sensitivity study showed that, as a rule, the strains were sensitive to the used antimicrobials. PMID- 2099860 TI - [Dermatosis in a girl with an orthopedic corset]. PMID- 2099861 TI - [Constitutional syndrome and pain in the cervical column]. PMID- 2099863 TI - [Meningitis caused by Candida tropicalis in a patient infected with human immunodeficiency virus]. PMID- 2099862 TI - [Gluteal abscesses caused by Brucella melitensis. Probable iatrogenic pathogenesis]. PMID- 2099864 TI - [Bacteremia caused by Salmonella arizonae in a patient with malaria]. PMID- 2099865 TI - [Meningitis caused by Candida albicans in a patient with AIDS. Treatment with fluconazole]. PMID- 2099866 TI - [Meningitis caused by Candida in an HIV-positive patient. A case with a fatal outcome]. PMID- 2099868 TI - [Bacteremia caused by Clostridium tertium in a female patient with aplastic anemia]. PMID- 2099867 TI - [Letter in response to "Necrosis of the Soft Tissues in the Vulva and Perineum"]. PMID- 2099869 TI - [Pericarditis caused by Campylobacter fetus fetus]. PMID- 2099871 TI - Low-energy collision-induced dissociation of protonated polyamino alcohol derivatives of peptides and N-terminal blocked peptides. AB - This investigation reports the low-energy collision-induced dissociation of the protonated molecules of polyamino alcohols, formed by chemical reduction of synthetic peptides and N-terminal blocked peptides, in order to evaluate its potential for peptide sequence determination. The --CH2--NH-- cleavage with charge retention on the N-terminus was prominent, and the entire sequence of ions produced in this manner was observed. Some of the sequence ions arising from - CH2--NH-- cleavage accompanied by migration of two hydrogens, and --NH--C alpha H - cleavage with charge retention on the C-terminus, also occurred prominently. In addition, a great number of internal fragment ions were produced in relatively high abundance; these provided supplementary sequence information and were, in some cases, critical in determining the sequence. The usefulness of this method was exemplified by its application to the sequence determination of bacterial lipopeptides. PMID- 2099870 TI - The metabolism of trimipramine in the rat. AB - Studies on the metabolism of the tricyclic antidepressant trimipramine, 5-(3 dimethylamino-2-methylpropyl)-10,11-dihydro-5H-dibenz[b,f]azepine, in the rat are described. Many metabolites of trimipramine (TMP) were isolated from rat urine after enzymatic hydrolysis and their structures were identified by a gas chromatographic/mass spectrometric method, before and after appropriate chemical derivatization. Besides unchanged TMP, 20 metabolites were characterized (underivatized, and after acetylation), of which 12 had undergone alicyclic (C10 or C11) oxidation. This is a hitherto unreported metabolic pathway for TMP in the rat. PMID- 2099872 TI - [Clinical aspects of brainstem infarction]. AB - Ischemic stroke in the vertebrobasilar arterial territory often presents stunning signs and symptoms, and poses little difficulty in the clinical diagnosis. But in less dramatic cases, it is often difficult to make accurate clinical diagnosis and to document the precise extent of an infarct. The purpose of the present study is to demonstrate clinicotopographic correlations in patients with various brainstem and cerebellar infarctions and to reevaluate the importance of bedside clinical examinations for understanding pathophysiology and planning management of the patient. One hundred forty-three patients with clinical diagnosis of the vertebrobasilar infarction confirmed by MRI were studied. MRI is superior to CT scanning in delineating areas of infarction in the territory of posterior cerebral circulation because of the three dimensional approach and the lack of bone artifact. MRI also allowed very precise clinicotopographic correlations even in patients with good recovery, in whom pathologic verification of the lesion is not possible. There are some restrictions of MRI diagnosis to detect the clinical features which change from hour to hour, because of the mechanical limitation in spatial resolution and of the temporal uncertainty of the lesions such as reversible edema or coincidental asymptomatic old lesions. Clinical importance of ocular signs (eg. skew deviation, gaze limitations, nystagmus, pupillary abnormalities and so on) was discussed. Some eye-movement abnormalities (eg. gaze paresis, MLF syndrome, 'one-and-a-half' syndrome, lateropulsion or contrapulsion of eyes, and vertical nystagmus at the primary position) served as useful localizing signs, and especially their consecutive observations were of importance for clinical local diagnosis. Clinical syndromes, caused by lacunar lesions located either in the supratentorial or in the infratentorial structures, such as pure motor hemiparesis and ataxic hemiparesis were also discussed. In some cases of these syndromes, MRI failed to document the precise lesion responsible for the episode due to the multiplicities of small asymptomatic lesions. Even in such cases, detailed clinical informations (temporal profiles of the episode, past medical histories, neuro-ophthalmic signs and so on) may enable the differential diagnosis. It is concluded that the use of new imaging techniques such as MRI may provide new insights in the diagnosis of cerebrovascular diseases, but the importance of clinical observations can not be overemphasized. PMID- 2099873 TI - [Neurological diseases in the aged]. AB - In this paper, I described clinical and basic problems on neurology of the aged patients. These studies have been done in various institutions with many co workers. 1) A PET study revealed some age differences on CBF, CMRO2, or CMRgl. But these results are not so rigid in which much of individual variations should be considered in interpretation. Calendar age is not always compatible to biological age. 2) Saccular aneurysms in the brain artery were found in 7.3% of 1200 routine autopsy series of the aged subjects. Aneurysms with external diameter exceeding 6 mm had been fatally ruptured in 14 (78%) of 18 subjects. 3) Variations of the pyramidal crossing are found responsible for bizarre clinical manifestations. Non-crossing component was more prominent in the right pyramidal tract; consequently, right pyramidal tracts including ventral and lateral one seemed to have more extensive representation in the spinal cord level. 4) I123 IMP SPECT study showed a reduced uptake in the area 4 or area 4-6 of the ALS patients. 5) I introduced a new simplified Wartenberg's maneuver, which is useful for detection of subtle pyramidal dysfunctions. 6) Cases with central pontine myelinolysis and those of paraneoplastic syndrome were presented with an emphasis on their patho-chemical mechanisms. 7) Lewis-Sumner syndrome showing multifocal persistent conduction block is not rare in the aged, in which we have already had some useful therapeutic methods. 8) Dementia complicated with neurodegenerative disease was discussed on its clinical and chemical features of mental disturbances. In ALS-dementia, CSF-homovanilic acid reduced significantly than in the control and L-dopa was effective in some patients. 9) Vascular and Alzheimer type dementias were presented and discussed on their pathogenetic mechanism according to our recent studies with review of literature. PMID- 2099874 TI - [Molecular pathology of Duchenne and Becker muscular dystrophy]. AB - The gene for Duchenne (DMD) and Becker (BMD) types of muscular dystrophy has been isolated by Kunkel's and Worton's groups and shown to be the largest one over known in human, spanning more than 65 exons distributed over 2,500 kb in P21 region of X-chromosome. Fourteen kb cDNA encodes 427 kD cytoskeletal protein "dystrophin", supposed to form an anti-parallel homodimer like alpha-actinin and spectrin. The polyclonal antibodies against the synthetic peptides or fusion proteins predicted from dystrophin cDNA disclosed the complete absence of dystrophin at the surface membrane of both skeletal and cardiac muscles of DMD in marked contrast with the continuous and uniform staining in normal muscles. In manifested carriers, the mosaic expression of dystrophin was observed at the surface membrane of the skeletal muscle. BMD, which is thought to be allelic to DMD, revealed a faint or patchy immunostaining along with the abnormal and/or lower amount of dystrophin. In BMD, there is an intimate connection between the amount of dystrophin and the severity of the clinical course. It should be noted that 5 out of 39 patients with clinical diagnosis of limb-girdle (L-G) muscular dystrophy showed a patchy staining pattern, suggesting BMD not L-G. On the basis of dystrophin discovery, a possible therapeutic trial of DMD is discussed. PMID- 2099875 TI - [Clinical feature and pathophysiology of compression myelopathy]. AB - In treating compressive lesions to the spinal cord, it is essential to understand underlying pathophysiology which causes compression myelopathy. When the spinal cord is compressed by static lesions, such as very slowly expanding extramedullary benign tumors, function of the white matter remains unaffected till later stage. Even in advanced cases, in which the function has been markedly affected, the function recovers remarkably following to surgical removal of the lesion. These phenomena have been proved by neurophysiological and clinical evidence. In cases with spondylotic myelopathy, dynamic factors, such as hyperextension of the neck, play more important role than the size of bony spurs, herniated discs or ossified posterior longitudinal ligament. In these cases, function of the white matter is more easily affected than in cases with static compression. The gray matter is more vulnerable than the white matter. In cases which exhibit slow finger opening, it was proved that the interneuronal connection was affected. In cases with myelopathy caused by overstretch mechanism, main lesion is limited to the gray matter. Based on several experimental works, it was suggested that venous engorgement probably is the main cause which affects the gray matter. PMID- 2099876 TI - [Pupil--recent development of investigation]. AB - This paper introduces recent development of investigation in the pupil system, in the Department of Ophthalmology, Kitasato University. Firstly, normal pupil parameters among various age groups (10 years to 70 years old) were studied by a new infrared videopupillography (Iriscorder C-2515). The parameters studied were pupil area in darkness, and other various parameters followed by photic stimulation (3000 troland) of the eye. Secondly, the pupil was studied by photographic method using infrared film under ordinary illuminated (500-800 Lux) room, and drug response especially pilocarpine of the pupil was studied and reviewed. Thirdly, a new information about pupil response followed by 0.06% pilocarpine instillation in patients under the brain death has been proposed. Denervation supersensitivity was obvious in 70% of the patient under brain death. Clinical significance of this pharmacological study has been emphasized especially for the determination of the brain death under comatose state of a given patient. PMID- 2099877 TI - [Clinicopathologic study of progressive subcortical vascular encephalopathy of Binswanger type (PSVE)]. AB - To investigate the histopathological basis of white matter pallor on myelin staining in PSVE, the frontal white matter was examined by electron microscopy in 7 cases with PSVE. The number of nerve fibres per unit area of the white matter was significantly less in PSVE compared with that in the control group or in senile dementia of Alzheimer's type (SDAT). Nerve fibers in PSVE had a tendency to have thinner myelin sheaths than in the control group or in SDAT, but the difference was not significant. The white matter pallor in PSVE is mainly based on the loss of nerve fibres. The dementia in PSVE is probably related to the loss of nerve fibres in the cerebral white matter. A sum of oligodendrocytes and astrocytes per unit area decreased in the area with white matter pallor. Main stem of cerebral arteries, leptomeningeal arteries, medullary arteries in the cortex, and small arteries or arterioles in the cerebral white matter were studied pathologically in 22 elderly patients with PSVE. Not only the severe hyalinotic changes of arterioles in the cerebral white matter, but also the diffuse atherosclerotic lesions in main stem of cerebral arteries and/or the stenotic lesions in leptomeningeal arteries were the characteristic arterial changes of PSVE. Angionecrosis was observed in 70% of the PSVE patients. To substantiate my hypothesis that PSVE in the elderly can be induced by the repeated hypotension or the greater variability of the casual blood pressure in the hypertensives, I studied retrospectively the casual blood pressures in PSVE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099878 TI - [Pathogenesis and pathophysiology of ischemic leukoencephalopathy]. AB - The cerebral white matter is highly susceptible to ischemic damage because of its location in the end-fields of penetrating arteries. Our studies have shown that hypertension, short-term variability of blood pressure, decreased oxygen dissociation of hemoglobin, and increased resistance of cerebral arterioles play important roles in the pathogenesis of Binswanger type dementia. While hypoperfusion was most remarkable in the frontal area and dopamine metabolism in the cerebrospinal fluid was impaired in Binswanger type dementia, cerebral blood flow decreased most conspicuously in the parietal area and there was an impairment of noradrenaline metabolism in the cerebrospinal fluid in senile dementia of Alzheimer type. Previous anatomical studies have indicated that the ascending dopaminergic system predominantly innervates the frontal cortex, while the noradrenergic system projects all cortical areas, including the parietal cortex. Our findings suggest frontally-dominant dysfunctions in Binswanger type dementia. PMID- 2099879 TI - [Leuko-araiosis--regional cerebral hemodynamics]. AB - To investigate the cerebral hemodynamics of leuko-araisosis (L-A), we made SPECT measurement of regional cerebral blood flow (rCBF) in 31 patients with L-A. Cerebral vascular reactivity to carbon dioxide and blood pressure was studied. Changes in rCBF during sleep were also studied. SPECT measurements of rCBF were made using radioactive tracer I-123-iodoamphetamine and Tc-99m-HMPAO. Regional CBF was reduced in patients with L-A in the white matter and in the frontal and the parietal cortex. Cerebrovascular CO2 reactivity was impaired in the white matter but was preserved in the frontal and parietal cortex. Cerebral blood flow autoregulation was impaired in the frontal cortex and in the parietal cortex. During sleep (stage 2-3) rCBF was reduced most markedly in the frontal and in the parietal cortex. Blood pressure was also reduced during sleep suggesting that the reduction of rCBF in L-A was partly due to dys-autoregulation. PMID- 2099880 TI - [Significance of periventricular hyperintensity on magnetic resonance images in stroke patients]. AB - To clarify the significance of periventricular hyperintensity (PVH) on MRI-T2 images in stroke patients, clinical and experimental studies were performed. MRI (1.5 Tesla) was obtained in 153 patients with ischemic stroke. The PVH was observed in all the patients, although severe PVH was found only in 22% of the cases. Severe PVH was observed mainly in hypertensive elderly patients with multiple infarctions and impaired cognitive function. Regional cerebral blood flow was reduced in majority of these patients. The absence of aqueductal signal flow void, remarkable ventricular enlargement and abnormal RI cisternography+ were observed in 20% of the patients with severe PVH. In Wistar rats and gerbils, chronic low perfusion state was induced by occlusion or narrowing of both common carotid arteries, and histological studies were performed at 1 week, 1 month or 3 months after the surgery. Multiple infarctions, white matter changes and ventricular enlargement were observed in these animals. The results suggest that chronic low perfusion in the brain and/or abnormal cerebrospinal fluid circulation play a role in the development of PVH. PMID- 2099881 TI - [The significance of cerebral white matter lesions in vascular dementia--from psychiatric aspects]. AB - The significance of cerebral white matter lesions in vascular dementia was mentioned, based on the findings of 50 autopsied cases at Yokuhukai Geriatric Hospital. Neuropathology of vascular dementia is classified to 5 types, i.e. 1) lacunar type, 2) cortical type, 3) cortico-white matter type, 4) white matter type, and 5) Binswanger type. Our findings on 50 patients revealed no lacunar type, cortical type in 8 cases, cortico-white matter type in 19, white matter type in 9, and Binswanger type in 14. The fact that 42 patients out of 50 showed some lesions involving the cerebral white matter suggested the important role of the white matter lesions in the pathogenesis of dementia of vascular type. Our cases also indicated that Binswanger type be commonly observed, although dementia of this type has been thought to be very rare since Binswanger (1894) and Alzheimer (1902) had reported similar patients. The patients with cerebral white matter lesions develop more marked dementia, especially of frontal and parieto occipital type, than ones with cortical lesions, but the characteristics of symptoms of white matter and Binswanger type remain to be fully clarified. PMID- 2099882 TI - [Ischemic neuropathy]. AB - Ischemia plays an important role in the development of neuropathies associated with various disorders, such as peripheral vascular occlusive diseases, necrotizing vasculitides, diabetes mellitus and nerve compression or trauma. Although a multiple mononeuropathy or an asymmetrical polyneuropathy is the usual clinical presentation of ischemic neuropathy, some patients present with a neuropathy that is mainly distal and symmetrical. Pathologically, nerve ischemia results in focal or multifocal central fascicular or sector fiber degeneration. These ischemic lesions tend to begin at mid-upper arm or midthigh level, which is the watershed zone of poor perfusion, and become more diffuse distally. Nerve ischemia at the level of distal small fascicles often induces sub-perineurial crescent lesion rather than central fascicular fiber degeneration. Physiologically, reduced nerve blood flow with endoneurial hypoxia has been demonstrated in experimental diabetic and galactose neuropathies. Endoneurial ischemia/hypoxia in galactose neuropathy appears to be due to increased intercapillary distances and constriction of trans-perineurial vessels resulting from endoneurial edema. Although acute ischemic neuropathy has been well investigated, little is known about functional or structural responses of peripheral nerve to chronic ischemia. PMID- 2099883 TI - Hemolysis mechanism of dental adhesive monomer (methacryloyloxydecyl dihydrogen phosphate) using a phosphatidylcholine liposome system as a model for biomembranes. AB - To clarify the mechanism of interaction of dental adhesive monomers with biological membranes at the molecular level, we studied the interaction of methacryloyloxydecyl dihydrogen phosphate (MDP) and methacrylic acid (MAA) with the dipalmitoylphosphatidylcholine (DPPC) liposome system using NMR and DSC. MDP DPPC interaction became apparent through broadening of the DPPC phase transition as pH decreased, finally the enthalpy of MDP-DPPC (1:1 mol ratio) reduced to zero at pH 2.5. Proton chemical shifts of MDP enhanced shielding and proton signals due to the phosphatidylcholine polar group (O-CH2-CH2-N bond) of DPPC were observed. MAA-DPPC interaction was smaller than that of MDP-DPPC, even at low pH. It was concluded that the strong hemolytic activity of MDP may be due to its interaction with the phospholipid bilayers of erythrocyte membranes. PMID- 2099884 TI - Heat curing behavior of light-cured composite resins investigated by dynamic differential scanning calorimetry. AB - The heat curing behavior of light-cured restorative composite resins, light-cured crown and bridge veneering resins, pure dimethacrylate monomers, Bis-GMA monomers containing various initiators, and monomer mixtures were investigated by slow heating at a constant rate with differential scanning calorimetry (DSC) without any light irradiation--the so-called dynamic DSC measurement. Some of the light cured restorative composite resins and the light-cured crown and bridge veneering resins showed a sharp exothermic peak due to heat curing. Pure TEDMA also showed a sharp exothermic peak, whereas the Bis-GMA monomers containing catalysts for light curing showed no exothermic peak. It seems that heat curing behavior of light-cured composite resins depends not on the decomposition of camphorquinone, but on that of the monomer itself. PMID- 2099886 TI - New method of treatment for dentin hypersensitivity by precipitation of calcium phosphate in situ. AB - The hydrodynamic theory is generally accepted as an explanation of hypersensitive dentin and suggests that occlusion of exposed dentinal tubules should result in a reduction of hypersensitivity. We tried to block tubules by in situ precipitation of insoluble calcium phosphate. Calcium phosphate crystals precipitated in situ on patent dentin surfaces and formed in the tubules immediately upon serial application of sodium phosphate and calcium chloride solutions, thus occluding the tubules. The size of crystals, their degree of coverage, and the thickness of the precipitate depended on the method of application and concentration of the solutions. The application of 5% disodium phosphate solution followed by rubbing with 10% calcium chloride solution resulted in immediate relief from dental hypersensitivity in 84% of patients treated. PMID- 2099885 TI - Clinical evaluation of the sedative effect of HEMA solution on the hypersensitivity of dentin. AB - The sedative effect of the dentin primer, 35% hydroxyethyl methacrylate (HEMA) solution, on dentin hypersensitivity was clinically evaluated. Exposed root surfaces of teeth were cleaned with neutralized 0.5 mol/L EDTA and treated with 35% HEMA solution followed by the application of a commercial dentin bonding agent. The extent of sedation was estimated by comparison of the responses before and after treatment to irritation by a cold water spray, compressed air blast and scratching with an explorer. The degree of the response to these irritations was decreased significantly upon the combined application of HEMA and commercially available dentin bonding agents though it was still ineffective in nearly 30% of the 48 cases tested. PMID- 2099887 TI - Effects of zirconia addition on fracture toughness and bending strength of dental porcelains. AB - Zirconia dispersed composite porcelains with glass and aluminous porcelain as matrix were prepared as models of dental porcelains. The bending strength and fracture toughness of the composite porcelains were examined. The bending strength and fracture toughness of composite porcelains containing 50 wt% zirconia were 20 to 80% greater than in glass alone. However, bending strength and fracture toughness decreased upon the addition of zirconia at more than 50 wt%. Moreover, in the case of aluminous porcelain as matrix, fracture toughness increased to a maximum value of 2.6 M Pa.m1/2by addition of 23 wt% zirconia, twice the toughness of glass alone. On the other hand, no increase of bending strength was observed in this case. Deflection and bowing of cracks as well as microcracking effects were related to these increases of mechanical properties in zirconia dispersed composite porcelains. PMID- 2099888 TI - Viscosity of dental porcelains in glass transition range. AB - Changes in the viscosity of dental porcelain as a function of temperature are the controlling factor determining incompatible stresses in porcelain-fused-to-metal restorations. A new method was used to estimate viscosity using a viscoelastic analytical model that considers the relation between the heating rate and deformation temperature (Td) of dental porcelain with stress applied during heating. The activation energy of viscous flow and the viscous constant in the Arrhenius equation were calculated for six kinds of commercial body and opaque porcelains. The effect of the heating rate on the instantaneous coefficient of thermal expansion was also measured. Tg onset was graphically determined using data on thermal deformation and agreed well with the strain point as defined by viscosity. The data gathered in this study was also compared to the experimental results of previous works by others. PMID- 2099889 TI - Improvements to light transmittance in light-cured composite resins by the utilisation of low refractive index dimethacrylates. AB - In an effort to improve the light transmittance of light-cured composite resins while avoiding degradation of their physical properties, 4 dimethacrylates having low refractive indices and a bulky backbones such as alicyclic or fluorine substituted bisphenol groups were synthesized. The depths of cure and physical properties of 6 experimental composite resins containing these new monomers were, then, examined and compared to those of 3 control composite resins containing UDMA, BisMEPP, or BisGMA. The depths of cure of the experimental group containing the synthesized monomers were greater than those of the control group with the exception of the composite containing UDMA. The depth of cure increased as the difference between the refractive indices of the matrix monomer and silica filler decreased. The physical properties of 2 composites in the experimental group were comparable to those of the control group. The matrix monomers of these 2 composites were a mixture of 4,8-dimethacryloxymethylene tricyclo [5.2.1.0] decane or 2,2-bis (4-methacryloxyethoxy phenyl) hexafluoropropane and TEGDMA in a molar ratio of 1/1. PMID- 2099890 TI - Chronopharmacological actions of the pineal gland. AB - In all mammalian species studied to date, the pineal gland shows a pronounced circadian rhythm with high activity at night and very low activity in daytime, as reflected in the output of its hormone, melatonin. The pineal is one of the few organs which can synthesize melatonin and, under normal circumstances, is virtually the only source of circulating melatonin. Pineal activity is tightly controlled by the light/dark cycle, in such a manner that melatonin can convey information to the organism on the length of the dark phase of the photoperiod. In seasonal breeding species, the 24 hour pattern of secretion of melatonin shows seasonal changes which are crucial for determining the timing of seasonal changes in bodily function. In man, alterations in pineal function are of significance in jet-lag, shift work and in affective disorder. PMID- 2099891 TI - Biochemistry of the pineal gland as an endocrine organ. AB - Experimental studies established a relationship between the pineal gland and various tumors a long time ago. Pineal extracts inhibit a wide spectrum of experimental tumors. Moreover, melatonin shows an anti-tumor action in both intact and pinealectomized animals. We have found that serum melatonin content is increased by 4 to 5-fold in melanoma patients. In normal subjects serum melatonin ranges from 0.47 to 0.65 nmol/l or 1.44 to 2.14 pg/mg serum protein. In contrast, in melanoma patients melatonin content of the serum varies between 2.07 to 6.20 nmol/l or 9.70 to 20.86 pg/mg serum protein. In another study, controls had melatonin levels of 0.47 +/- 0.02 nmol/l serum, or 2.07 +/- 0.24 pg/mg serum protein. In melanoma patients, the melatonin level was 1.65 +/- 0.10 nmol/l serum or 9.82 +/- 1.02 pg/mg protein. Post-mortem examinations revealed that the pineal pigment content was inversely related to the prevalence of malignancy, suggesting that a high melatonin level may be associated with an oncostatic action. Hydroxyindole-O-methyltransferase activity was significantly higher in the pineal gland of subjects that died from malignant tumors as compared with subjects that died from other causes. PMID- 2099892 TI - Neuropharmacology of pineal secretions. AB - A connection between pineal function and several psychiatric diseases has been shown recently. The diurnal and seasonal rhythmicity of melatonin production is associated with affective disorders and several types of endogenous depression. The cortisolmelatonin ratio was significantly higher in depressed individuals than in healthy controls. Alterations in melatonin secretion may also occur in non-affective psychiatric disorders, such as chronic schizophrenia. Antidepressants and other psychotropic drugs modify melatonin synthesis. In rodents, monoamine oxidase (MAO) inhibitors (e.g. pheniprazine, harmine or nialamide) increase pineal concentrations of the melatonin precursors, serotonin (5HT) and N-acetyl serotonin (NAS), by enhancing N-acetyl transferase activity. These drugs also increase melatonin, 5HT and NAS in the cerebrospinal fluid. Chronically administered tricyclic antidepressants reduce pineal and serum melatonin content in rodents. In humans, both the MAO-A selective inhibitor clorgyline and the non-selective inhibitor tranylcypromine increase serum melatonin levels. In contrast, serum melatonin remains unaltered by the MAO-B selective inhibitor L-deprenyl. The actions of other drugs on melatonin production, including lithium, propranolol, amphetamine and several monoamine precursors, are in accordance with their psychotropic effects and with their effect on monoamine functions. PMID- 2099893 TI - Oncostatic effects of the pineal gland. AB - There is increasing evidence that the pineal gland has a role in the control of neoplastic processes. Kerenyi found hyperplasia of the pineal gland in patients with widely disseminated malignant melanoma. Feuer and Kerenyi reported significantly higher serum melatonin levels with malignant melanoma. Beral et al. found 2.1 times increased risks of melanoma and Pasternak et al. described a relative risk of 1.87, related to exposure to fluorescent light. In our study, white New Zealand rabbits were exposed for 12 months to fluorescent light. The serum melatonin levels of the control group were significantly higher, p less than 0.005. According to Cohen, the pineal gland has a role in the etiology of breast cancer. Melatonin inhibits MCF-7 human breast cancer cell growth in culture. In our study of 500 surgically removed breast tumors, 254 were melatonin receptor positive, 246 negative. Most melatonin receptor positive breast cancer occurred between 60-65 years of age, receptor negative breast cancer peaked between 40-45 years. Benign breast tumors were almost invariably melatonin receptor positive. It is proposed that melatonin may have a direct effect on breast tumors, the melatonin receptors being the probable sites of interaction between melatonin and the tumor cell. PMID- 2099894 TI - Ethical boundaries of medical research in infants and children in the 80s: analysis of rejected protocols and a new solution for drug studies. AB - To assess the difficulties in conducting pediatric research, we reviewed the 351 protocols dealing with research in infants and children in our institute between July 1982 and August 1988. Of the 16 rejected protocols (4.5%), 12 were drug studies, 3 dealt with the nature of course of disease states and 1 was in the area of behavioral sciences. Drug studies were significantly more likely to be rejected than all other studies. The most common reason for rejection (n = 10) were major scientific flaws which, according to the committee, would result in inability of the study to answer the questions posed by the researchers. In 9 cases, the committee judged a study to be physically invasive without a direct benefit to the involved infant/child. In 3 cases, the committee rejected a study because patients with serious medical conditions might be randomized to receive placebo and not a drug which, based on current knowledge from adults, would possibly improve their condition. In 3 protocols current antimicrobial therapy covered all pathogens causing the infection and the proposed new therapy could not improve the prognosis further but only be equal or inferior. Researchers who had more than one protocol rejected had submitted significantly more protocols (7.17 +/- 1.35) than those who had only one rejection (1.86 +/- 0.36, p less than 0.0005) or than the 10 researchers with the highest number of studies without a single rejection (4.2 +/- 0.4, p less than 0.05). In trying to solve the problem of invasiveness in drug studies in neonates, we have conducted a pharmacokinetic analysis and have documented that 3 samples for drug concentration are all that is needed for pharmacokinetic analysis, as values achieved with these data are not different from those calculated from 8 concentration-time points. In a prospective study in neonates, the validity of these assumptions was proven for the use of the antibiotic vancomycin. This model may be applicable to other areas of pediatric research where careful analysis of existing data may reveal that accurate information can be derived from much fewer samples than previously believed. PMID- 2099895 TI - Pain in the newborn--pharmacodynamic aspects. AB - Pain is subjective and can be quantitated in others only through cognitive cooperation between the sufferer and the observer. The newborn infant can neither describe pain nor remember it later in life. Thus, strictly speaking, we will never know if a pain experience can occur in the newborn period. However, many observations suggest that a nociceptive function exists at birth: (1) the neuronal pathways and transmitter systems required for pain conduction in adults seem to be present already during fetal life: (2) noxious stimulation of the newborn leads to behavioural responses and stress-related biochemical changes, and (3) the use of anaesthetic and analgesic drugs may improve the clinical outcome following surgery. The main features of the pharmacokinetics in the newborn period of both peripherally and centrally acting analgesics are now relatively well known and at least the short-term side effects are predictable and generally avoidable. Even if long-term adverse drug effects due to impaired imprinting have been suggested it appears that nociceptive stimuli in the newborn should be considered being disadvantageous to the patient. If they cannot be avoided, they should be treated. PMID- 2099896 TI - Treatment of growth hormone insufficiency. AB - Growth during childhood is growth hormone dependent and is modulated predominantly by the amplitude of the growth hormone secretory bursts while the frequency of these episodes remains relatively constant at 180-200 min. Optimisation of therapy for children with growth hormone insufficiency requires a clear definition of the dose of the growth hormone required to promote growth which in severely insufficient children is at least 20 U/m2 body surface area/week. The frequency of administration of growth hormone is equally important in determining response, and interpretation of any result of therapy condition that is being treated also needs to be carefully considered. Children with Turner's syndrome will not have the same growth response as children who have classical growth hormone insufficiency. PMID- 2099898 TI - Micronutrients and drug response: vitamin A and vitamin E in the fetus and in the newborn. AB - Major advances on the therapeutic use and the toxicity of two fat-soluble micronutrients, vitamin A and vitamin E, have taken place in recent years. High dosages of vitamin A and retinoids are teratogenic. The use of isotretinoid in pregnancy is associated with a high risk of congenital malformations. Retinoid metabolites (4-oxo-transretinoic acid and retinyl palmitate) have been related to teratogenicity. Studies in premature infants support the concept that supplementation of vitamin A (to achieve normal serum retinol concentrations) reduces the pulmonary damage caused by hyperoxia. Much controversy has surrounded the use of vitamin E in the low-birth-weight infant. Accumulation occurs with repeated administration and serious toxicity ensues. Thus, on the side of potential therapeutic applications, injudicious use of these vitamins is associated with previously unsuspected toxicity in the fetus and newborn. PMID- 2099897 TI - Nutritional correlates of fetal growth. AB - Fetal growth is regulated by an interplay of genetic and environmental factors. Fetuses with growth restriction secondary to decreased nutritional supply exhibit maturation whereas hyperglycemic fetuses of diabetic mothers show delayed lung and placental maturation. Membranes from fetuses of diabetics have a decrease in epidermal-growth-factor (EGF) binding, whereas EGF binding is increased in lung and placenta of growth-restricted fetuses. These results suggest that the EGF receptor is responsive to altered nutritional states and may be important to substrate flow to the fetus. PMID- 2099899 TI - Neuroteratological consequences of chronic low-level lead exposure. PMID- 2099900 TI - Prenatal diagnosis and treatment of adrenogenital syndrome (steroid 21 hydroxylase deficiency). AB - Prenatal treatment of pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency was carried out in conjunction with chorionic villus sampling (CVS) in the first trimester for analysis of restriction fragment length polymorphisms. Dexamethasone administration to the pregnant woman was initiated at a mean gestational age of 7 weeks (range 4-10 weeks) before testing to determine whether the fetus was affected with 21-hydroxylase deficiency, and CVS was performed at a gestational age of 8-10 weeks. Two affected female fetuses were identified by molecular genetic techniques among this group. The duration of unnecessary prenatal dexamethasone treatment for unaffected or male fetuses was substantially reduced in the CVS group compared with a cohort of 8 prenatally treated pregnancies where amniocentesis was performed in the early second trimester. No major morbidities were observed in the treated pregnancies. Postnatal confirmation of CVS diagnosis was obtained in all cases where DNA from an affected sibling was available for comparative analysis with the DNA from chorionic villus tissue. The external genitalia of the affected females who were treated prenatally appeared normal. Based on these data we conclude that the benefit:risk ratio is favorable for prenatal administration of dexamethasone in pregnancies at risk for 21-hydroxylase deficiency. Treatment should be initiated during the first trimester in conjunction with diagnosis by CVS/molecular genetic techniques. Long-term postnatal surveillance is recommended for all offspring of dexamethasone-treated pregnancies. PMID- 2099901 TI - Effects of prenatal treatment with phenobarbital. AB - Phenobarbital, when administered prenatally to animals, produced profound and prominent effects on reproduction. Preliminary analysis of a unique cohort of adolescents who were exposed to phenobarbital in utero suggests that long-term effects may be evident in the human as well. PMID- 2099902 TI - Interaction of granulocytes and endothelial cells upon stimulation with tumor necrosis factor-alpha: an ultrastructural study. AB - By the production of microbicidal agents, such as reactive oxygen species, activated PMN are capable of inducing tissue damage in the host. TNF-alpha was recently shown to be a potent activator of PMN oxidative metabolism. To further evaluate the interaction between activated PMN with physiological target cells, the effect of human PMN on cultured bovine aortic and human umbilical vein endothelial cells (EC) upon stimulation with human TNF-alpha was investigated by ultrastructural techniques: Scanning and transmission electron microscopy (SEM and TEM resp.) and ultrastructural detection of H2O2 production. When isolated PMN were added to EC in the presence of recombinant human TNF-alpha (10(3) U/ml) the EC-monolayer was disrupted within 4 h and EC changed their shape by exhibiting a spindle-like structure. PMN were seen in the intercellular spaces. Release of H2O2 was observed at the surface of the PMN plasma membrane, the luminal part of the small intracytoplasmic vacuoles in the PMN as well as in the contact zone between PMN and EC, but not within the EC. Scavengers of reactive oxygen species, such as superoxide dismutase and catalase or D-mannitol failed to block the effect of TNF-alpha-stimulated PMN on EC. In contrast, addition of NaN3 (0.1 mM), an inhibitor of myeloperoxidase activity, almost completely inhibited the disruption of EC-monolayers. Subsequent addition of NaN3-insensitive horseradish peroxidase reconstituted the effect. The results obtained suggest that TNF-alpha-stimulated PMN effectively cause the disruption of EC monolayers by an adherence-dependent mechanism which is mediated by the release of myeloperoxidase. The results may be of major importance for the pathogenesis of inflammatory vascular reactions. PMID- 2099903 TI - Comparative activation states of tumor-associated and peritoneal macrophages from mice bearing an induced fibrosarcoma. AB - Balb/c mice bearing a methylcholanthrene-induced fibrosarcoma were used to compare the activation levels of tumor-associated and peritoneal macrophages. Two stages of tumor growth were examined, namely "small" and "large" tumors, with average diameters of 10 and 30 mm, respectively. The activation state, determined by measurement of both phagocytic index and beta-glucuronidase content, was found to be markedly higher in tumor-associated macrophages than in their peritoneal counterparts and it was, in addition, independent of tumor progression. The percentage of tumor-associated macrophages, which were detected on the basis of Fc receptor expression, remained constant in the growing neoplasm, at approximately 23% of total cell population. None of these parameters were affected by inoculation with an immunopotentiating dose of heat-killed Candida albicans which, on the other hand, seemed not to alter the course of the tumor. These data suggest that within the tumor microenvironment macrophages would somehow be maintained at a constant proportion and at a highly activated state, while outside the tumor they would be at a lower activation level. Our results also suggest that TAM would not possess antitumor activity in vivo, although we have found this activity in vitro. PMID- 2099904 TI - A monoclonal antibody recognizing selectively rat granulocytes. AB - In the present study, a murine monoclonal antibody, RK-4 (IgG1) specific for rat granulocytes and their precursors in blood and bone marrow is described. Results obtained by immunocytological and flowcytometry analysis showed this mAb to recognize selectively a surface antigen on neutrophils, eosinophils and basophils. Analysis of cryosections of various lymphatic and non-lymphatic organs demonstrates that this mouse antibody does not cross-react with any other structures. By flow cytometric analysis we found peripheral blood leukocytes to consist of about 15-20% granulocytes. RK-4 is therefore a valuable tool for studying differentiation and function of granulocytes under various conditions. PMID- 2099905 TI - Characterization of Borrelia burgdorferi associated antigens by monoclonal antibodies. AB - In this paper, we present a series of murine mAb recognizing B. burgdorferi antigens. The antibodies were characterized by immuno-blotting and immuno fluorescence studies using isolates of B. burgdorferi from North America and Europe, respectively. Moreover, reactivity of the antibodies with recombinant B. burgdorferi flagellin and OspA was studied. The results suggest these anti-B. burgdorferi mAb as valuable tools for the serological analysis of B. burgdorferi isolates and for affinity-purification of the respective proteins. Moreover, these mAb appear suitable to classify antigenic variants of B. burgdorferi and to study the protective capacity of antibodies in a murine model for B. burgdorferi infection. PMID- 2099906 TI - Auto-MHC class II-reactive T cell line obtained from MRL/+mice suffering from "lpr-GVHD". I. Characterization of surface phenotypes, specificities and functions in vitro. AB - When MRL/Mp-(+)/+ (MRL/+) mice are lethally irradiated and then reconstituted with bone marrow or spleen cells from MRL/Mp-lpr/lpr (MRL/lpr) mice, they develop a graft-versus-host disease (GVHD)-like syndrome, colloquially known as "lpr GVHD". To analyze the roles of the MRL/lpr T cells in the development of "lpr GVHD" and autoimmune diseases, several T cell lines were established from the spleen cells of MRL/+ mice suffering from "lpr-GVHD". The surface phenotypes, specificities, and functions of a representative clone (l/+T1) of the cloned T cell lines were characterized. The l/+T1 cells showed Thy-1.2+, L3T4+ and T3+, but Lyt-2- and B220- phenotypes. Proliferative response was observed by co culturing the cells with spleen cells from MRL/+, MRL/lpr, AKR/J, and C3H/HeN mice, but not from BALB/c or C57BL/6 mice. Furthermore, the l/+ T1 cells responded to spleen cells of B10.BR and B10.A but not B10.D2 mice. The proliferative response of l/+ T1 cells to MRL/+ spleen cells was inhibited by anti-I-Ek (but not anti-I-Ak or anti-Kk) antibodies, suggesting that the specificity of l/+T1 cell culture enhanced the proliferative response only in the presence of appropriate stimulators. Treatment of stimulator cells with J11d.2 + C (but not anti-Thy-1.2 + C or 33D1 + C) abolished the stimulatory effect, indicating that B cells are effective stimulator cells for auto-MHC class II reactive l/+T1 cells. When MRL/+ splenic B cells were co-cultured with l/+T1 cells, both B cell proliferation and IgM production were observed. In addition, IgM-class rheumatoid factor and anti-ssDNA antibody activities were found in the supernatants of MRL/+ splenic B cells co-cultured with l/+T1 cells. These results are discussed in relation to "lpr-GVHD" and autoimmunity in MRL/lpr mice. PMID- 2099907 TI - T cell lines responding to Mycoplasma arthritidis and chondrocytes in the Mycoplasma arthritidis infection of rats. AB - CD 4+ T cell lines responding specifically to Mycoplasma (M.) arthritidis were established from spleen and lymph nodes of a Lewis rat infected with M. arthritidis. The T cell response to M. arthritidis was MHC class II-restricted. M. arthritidis-reactive T cell lines also responded to syngeneic chondrocytes suggesting that M. arthritidis and chondrocytes may share a common antigenic structure. The T cell lines reacting with chondrocytes may play an important role in the chronic stage of the M. arthritidis-induced arthritis of rats by maintaining immune reactions initiated by M. arthritidis antigens and originally established to eliminate the mycoplasmas. These autoimmune reactions could perpetuate after disappearance of the mycoplasmas and possibly last for the entire lifetime. PMID- 2099908 TI - A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease. AB - Sera of 64 patients with chronic inflammatory bowel disease (IBD) were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) using an indirect immunofluorescence technique on ethanol-fixed human neutrophil granulocytes. 20 of 34 sera (59%) from patients with ulcerative colitis (UC) produced a fine granular and perinuclear ANCA staining pattern (p-ANCA) clearly different from the typical diffuse and granular cytoplasmic ANCA fluorescence (c-ANCA, synonym ACPA) seen in active Wegener's granulomatosis (WG). The majority of the 20 p-ANCA positive UC patients had a high inflammatory disease activity. Among the 14 p ANCA negative UC patients nine were without steroids; five of them had active disease, two were inactive and two had previously undergone colectomy. The remaining five patients still had active disease but received steroids for more than 4 weeks. Only 3 of the 30 sera from patients with Crohn's disease (CD) showed positive p-ANCA reactions. To narrow the specificity of the p-ANCA reaction all 64 sera were tested by ELISA for antibodies against anti-proteinase 3 (WG specific) and on HEp-2 cells for antinuclear (ANA) and anticytoplasmic antibodies. Ten p-ANCA positive UC sera were also tested in a myeloperoxidase ELISA. Only one UC serum reacted positively in the proteinase-3-ELISA and another one produced a weakly positive anti-nucleolar ANA fluorescence on HEp-2 cells. None of the tested sera reacted with myeloperoxidase suggesting that the p-ANCA staining pattern of granulocytes is not restricted to anti-myeloperoxidase antibodies as reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099909 TI - Molecular analysis of genetically determined target organ abnormalities in spontaneous autoimmune thyroiditis. AB - We have shown in earlier studies, that the development of spontaneous autoimmune thyroiditis (SAT) in chickens of the Obese strain (OS) depends on the presence of both, two dominant genes coding for an altered immune regulation and one recessive gene responsible for the susceptibility of the target organ for the autoimmune attack. The product(s) of the latter is (are) still not known. The present study was aimed at identifying possible candidates of cellular components of the thyroid gland of OS chicken and its SAT susceptible parental Cornell C strain (CS) by high resolution 2-dimensional (2D) gel electrophoresis. For this purpose organ cultures of the thyroid, bursa, thymus and liver were established and the synthesized polypeptides were labelled by 35S-methionine. OS and CS organs were compared with those of healthy normal White Leghorn (NWL) controls. The autoradiographs of the 2D-gels obtained from individual samples after various labelling periods were subjected to comparative analysis. We have found both quantitative and qualitative differences of polypeptide spots between OS/CS and NWL organ samples, some of them specific for the thyroid gland. Although one has to be aware that in this multidimensional analytical approach numerous, still elusive pattern differences are revealed, the thyroid specific phenomena will be further scrutinized. PMID- 2099910 TI - Induction of tolerance to non-H-2 alloantigens is not restricted by the MHC molecules expressed on the donor cells in cyclophosphamide-induced tolerance. AB - A long-lasting skin tolerance to non-H-2 alloantigens has been reported to be readily induced, when the recipient mice were primed intravenously (i.v.) with 5 x 10(7) spleen cells (SC) plus 1.5 x 10(7) bone marrow cells (BMC) from the H-2 identical strains of mice, and treated intraperitoneally (i.p.) with 200 mg/kg CP 2 days later. The present study was conducted in order to clarify whether or not tolerance induction to non-H-2 alloantigens in cyclophosphamide (CP)-induced tolerance is restricted by H-2 alloantigens on donor cells. When BALB/c (BALB; H 2d) female mice were primed i.v. with fully allogeneic [H-2 plus minor histocompatibility (H) antigen-disparate C57BL/10 (B10; H-2b) female SC plus BMC and treated i.p. with CP 2 days later, the survival of H-2 identical B10.D2 nSnSlc (B10.D2; H-2d) female skin was moderately prolonged, but the survival of fully allogeneic B10 female skin was not. When semiallogeneic (B10 x B10.D2) (H 2bxd) female cells or H-2 identical B10.D2 female cells were used as the tolerogen, the survival of B10.D2 female skin was prolonged moderately or permanently, respectively. There was no significant difference between the prolongations of B10.D2 female skin graft survival in the BALB mice treated with the B10 cells followed by CP, and the (B10 x B10.D2) cells followed by CP. Similar results were observed in H-Y antigen-disparate combinations. These results strongly suggest that tolerance induction to non-H-2 alloantigens is not restricted by the products of donor MHC in CP-induced tolerance. PMID- 2099911 TI - Natural anti-self reactivity which maps to MHC class I genes. AB - Responder spleen cells of [B10.A(5R) x B10.A(2R)]F1 hybrid mice cultured in vitro with irradiated parental spleen cells, generate a cytotoxic T cell response which maps to the H-2Dd and H-2(K-I)b genes of the B10.A(5R) parent. Specific reactivity of (5R x 2R) cells to B10.A(5R) parental (P) stimulators and not to F1 hybrid or B10.A(2R) stimulators was also demonstrated as an F1 anti-P proliferative response. Generation of a (5R x 2R) anti-5R response has also been noted during 2 degrees in vitro anti-viral cytotoxic responses where (5R x 2R) cells from either ectromelia or Sendai virus primed mice have been stimulated in vitro with infected 5R cells, but not when stimulated with infected 2R or (5R x 2R) cells. The generation of these responses is dependent on the use of parental stimulators for F1 hybrid cells during in vitro culture. All data is consistent with the hypothesis that (5R x 2R) F1 cells are not tolerant of 5R cells, and of the 4-fold higher level of Class I H-2Kb/Dd antigens which they express. PMID- 2099912 TI - Combined treatment of osteosarcoma of the limbs at an advanced stage, including hyperthermic-antiblastic perfusion. AB - Between August 1983 and September 1986 18 patients affected with osteosarcoma of the limbs in which the extent of the neoplasm would normally have required amputation were treated by two cycles of intra-arterial infusion of CDDP, associated with methotrexate at high doses administered i.v., followed by a hyperthermic-antiblastic perfusion confined to the affected limb with CDDP at high doses. At the end, the patients were administered two more cycles of methotrexate at high doses and CDDP intravenously. The immediate response, evaluated in radiological, clinical and histological terms, was such that in 11 patients it was possible to obtain satisfactory results with conservative treatment alone. None of the patients developed local recurrence. PMID- 2099913 TI - The possibility of repair in joints deprived of hyaline cartilage. AB - Based on prolonged previous studies on experimental animals, the author used the method described in human beings. Segments of cartilage removed from the chondrosternal junction were used to cover joint surfaces in the tibial plateau deprived of hyaline cartilage due to wear phenomena. PMID- 2099914 TI - Arthroprosthetic reimplantation with bioceramics. AB - The study analyzes the results obtained in 50 cases of arthroprosthetic substitution surgery performed as a result of "aseptic detachment of the implant"; it involves a consecutive series of operations performed between 1979 and 1983. In all of the cases ceramic-ceramic cemented prostheses were implanted. The results, which were generally satisfactory, confirmed the excellent properties of alumina (low wear, elevated tolerance). PMID- 2099915 TI - Intramedullary osteosynthesis 3. Kuntscher nailing in the humerus. AB - With regard for the principles that govern the correct application of intramedullary osteosynthesis in the long bones of the lower limb, the authors also support its use in the humerus. After an exhaustive survey of the specific problems at this site, a critical review of 130 cases observed over the last 15 years is reported. Extremely favourable results emerged in the treatment of the humerus with this means of synthesis, thanks to its surgical, mechanical and biological advantages. PMID- 2099916 TI - Radial shortening with osteosynthesis in the treatment of Kienbock's disease. AB - Since 1970 we have been using an original method of epiphyseal osteotomy to produce radial shortening in the treatment of Kienbock's disease. This is based on the experience of treating unstable Colles fractures with 2 transcutaneous Kirschner wires; they consolidate easily and quickly. The advantages are: a radial dorsal approach and an operation which is easily performed; an increase in the vascularization induced in the proximal area of the lunate; reduction of immobilization to 3-4 weeks; absence of complications which are common in other methods; immobilization limited to the wrist alone; resumption of work after 6-8 weeks; radial shortening of 5-8 mm with effective dynamic and static unloading and better trophism of the lunate; regression of pain and recovery of prehensile power in the hand in 28 cases followed up for 5 to 16 years after surgery. PMID- 2099917 TI - Indications for early surgery in cases of lumbar and dorsolumbar scoliosis: the role of vertebral rotation. AB - There are very few objective criteria for the choice between conservative and surgical treatment of lumbar and dorsolumbar scoliosis ranging from 40 to 50 degrees. We reviewed the long-term results obtained in 76 patients treated with plaster braces because they had refused surgical treatment; in 56% of the cases a nearly 10 degree gain was maintained after the onset of treatment; all of the cases which showed improvement presented a reduction in the curve by at least half and rotation by at least one-third in tests in suspension or in bending, and this was maintained in plaster. In cases where the long-term results were poor, however, rotation did not change. In conclusion, of the many parameters examined, only a combined assessment of the reducibility of both the Cobb angle and of rotation provides a valid indication for the treatment of lumbar and dorsolumbar curves ranging from 40 to 50 degrees. PMID- 2099918 TI - Comparison of the Hoffmann-Vidal external fixator and the Ilizarov apparatus in the treatment of open fractures of the tibia. AB - In order to compare the effectiveness of the Hoffmann-Vidal external fixator and the Ilizarov compression extension apparatus, the authors compared two homogeneous groups of 25 patients, selected by the computer, with open fractures of the mid third of the tibia. Clinical and radiographic comparison provided the important data necessary for an evaluation of the reliability of the two methods. PMID- 2099919 TI - The treatment of Kohler's second syndrome by continuous skeletal traction. AB - Osteochondrosis of the head of the second metatarsal bone, also known as Kohler's second disease, is typical of the second decade of life. This disease is characterized by evident symptoms during its acute phase, successively resulting in permanent changes in the metatarsal head. The authors propose a new method which is easy to use and which leads to rapid resolution of the osteochondrosis as well as to a rapid resumption of normal life and sports activity. PMID- 2099920 TI - Intramedullary osteosynthesis. 4. Kuntscher nailing in the ulna. AB - Intramedullary osteosynthesis with Kuntscher nailing is an appropriate and extremely effective operation in the treatment of diaphyseal fractures of the ulna. Like the other long bones of the limbs (femur, humerus, tibia), in the ulna, as well, the advantages of the method, particularly when performed in closed surgery, are undeniable, so much so that this bone has a shape which is particularly favourable to nailing. The authors present and discuss their personal series of cases reporting results which are excellent. Thus, once again, the great reliability of this simple means of synthesis, in use for more than 20 years, is emphasised, and the subject is completed with a series of previous technical suggestions on how to obtain the best results. PMID- 2099922 TI - Morphological aspects of the synovial membrane and the femoral epiphyseal nucleus in anemia induced experimentally (note 1). AB - The authors describe the macroscopic and ultra-structural changes in the synovial membrane and the growth nucleus consequent to anemia induced experimentally. In the anatomical region studied an early and a late response to the transitory anoxia is observed. The former is represented by the accentuation of the macrophagic activity of the A synoviocytes and by pictures of trabecular fragmentation. The latter is represented by hyperplasia of the synovial membrane, a reduction in the thickness of the joint cartilage, and by early and patchy calcification of the epiphyseal disc. PMID- 2099923 TI - A rare case of primary lymphoma of bone of cervical localization. AB - A rare case of primary lymphoma of bone localized in the epistropheus is reported. After emphasizing the difficulty of diagnosis based solely on clinical, radiographic and laboratory data, the authors stress that biopsy is essential to diagnosis. The excellent clinical result, followed up after 5 years, was obtained with surgical excision followed by antiblastic treatment with repeated cycles of VBD, and local and regional lymph node radiotherapy. PMID- 2099921 TI - Baropodometric studies in patients submitted to Grice-Green operation for primary valgus pronated flat foot. AB - This study reports the results of a computerized baropodometric analysis of the function of primary valgus pronated flat foot submitted to talocalcanear arthrodesis according to the Grice-Green method (Grice, 1952; 1955) as modified by Vigliani et al., (1978). Our purpose was to document any anomalies in the behaviour of such feet, which up until now have been based on conventional evaluation (plantar imprints, podoscopy, etc.), which are much less sensitive than those of modern electronic systems. PMID- 2099924 TI - A case of monolateral duplication of the Achilles tendon due to an anomaly of the medial gastrocnemius muscle. AB - The authors describe the chance finding of a congenital morphological anomaly in the Achilles tendon, characterized by monolateral duplication as a result of anomalous differentiation of the medial gastrocnemius muscle. This may be added to the previous congenital deformities described in the literature (shortness of the Achilles tendon, its duplication as a result of the lack of fusion of the aponeurosis of the soleus and of the gastrocnemii, the presence of a supplementary medial gastrocnemius). PMID- 2099925 TI - A case of osteoporosis associated with adenosine deaminase deficiency. AB - The authors report a case of early and marked osteoporotic syndrome in a patient affected with adenosine-deaminase deficiency (ADA) of the heterozygotic type. The negative results obtained in all the tests carried out to ascertain any dysmetabolic, nutritional or iatrogenic disease, and the literature reporting homozygotic patients with osteometabolic and skeletal changes similar to those observed in this particular patient, led the authors to suggest a possible pathogenetic role in ADA deficiency. They conclude by describing the mechanisms by which this enzymatic defect could determine the clinical picture, and by presenting a possible type of treatment. PMID- 2099926 TI - Arthroscopy in the treatment of osteochondrosis dissecans of the talus. AB - This study consists of six cases of osteochondrosis dissecans of the talus (ODT) treated with arthroscopy, which was able to precisely evaluate the integrity of the articular surface; this exact evaluation confirmed in turn the inaccuracy of radiographic staging and often even the most sophisticated techniques (CAT scan and/or MRI). Arthroscopy allows treatment of osteochondral lesions and consensual reactive synovitis in both advanced stages and minor lesions, with recourse to transchondral perforation. Its low morbidity and short period of rehabilitation together with the subjective and objective outcome at the follow-up (4-33 months) make arthroscopy a valid alternative to arthrotomy for treating this type of lesion. PMID- 2099927 TI - Results of reconstruction of the anterior cruciate ligament with the tendons of semitendinosus and gracilis in acute capsulo-ligamentous lesions of the knee. AB - This report presents the mid-term results of 55 cases of anterior cruciate ligament (ACL) lesions surgically treated in "acute phase" using intra-articular transfer of the semitendinosus and gracilis tendons, performed at the First Orthopedic Clinic of "La Sapienza" University in Rome since 1979. The follow-up is based on clinical (point system comprising subjective and objective criteria), instrumental (KT-1000 arthrometer), and radiographic (comparative AP view radiographic exam of the knees under load) data. On the basis of the results obtained, ACL reconstruction with the semitendinosus and gracilis tendons in the treatment of acute lesions can provide the patient with a good possibility of complete functional recovery of the knee. PMID- 2099928 TI - Extraarticular reconstruction in the treatment of chronic lesions of the anterior cruciate ligament. AB - The authors report the results of 40 patients treated with Lemaire extraarticular reconstruction for chronic anterior instability of the knee. The rate of success was 80%. The negative results did not have one single explanation, but were caused by either objective or subjective factors depending on the case. In evaluating the results in relation to the follow-up, a deterioration of the good results over time was observed (62.5% after 5 years). The Lemaire reconstruction is recommended for patients over 40 with moderate laxity who occasionally take part in athletic activity. PMID- 2099929 TI - Derotation osteotomy in the treatment of congenital dislocation of the hip: a review of long-term results. AB - The authors clinically and radiographically evaluate the long-term results of 257 femoral derotation osteotomies performed between 1959 and 1970 for congenital dysplasia and dislocation of the hip. Tracing the patients was very difficult because of the prolonged follow-up, yet a group of 36 patients was finally gathered. These patients were then uniformly studied and classified through precise quantification, with a numeric reference value, of clinical deficits and radiographic changes. The evaluation of the results confirmed that the effectiveness of femoral derotation osteotomy depends upon its timeliness, correct execution, and potential association with corrective surgery of the acetabular dome. Finally, both preexistent joint damage and the presence of genetic factors in the disease, which often causes relapse in spite of a technically perfect operation, are very important in determining the final result. PMID- 2099930 TI - The treatment of infantile coxa vara with the external circular fixator. AB - Coxa vara worsens as it evolves, and is often accompanied by other femoral deformities, such as hypometria, axial knee deviations, and rotational deformity. Traditional surgical techniques, especially intracapsular femoral neck osteotomy, are difficult to execute and often cause joint stiffness while not sufficiently correcting the coxa vara or the other deformities, in particular hypometria. For these reasons this study used the external circular fixator to simultaneously correct these deformities. The results are presented after discussion of technical details. PMID- 2099931 TI - Cemented arthroprosthesis in femoral neck fractures. AB - Primary total hip replacement in femoral neck fractures is still controversial. This report presents the findings of a study of 42 femoral neck fractures treated with cemented arthroprosthesis with an average follow-up of five years. The patients were divided into two groups according to the type of prosthesis, the reaming and cementing techniques, and the type of operating room. Each group had positive results in about 80% of the cases, testifying to the fact that arthroprosthesis is a valid method of treatment provided that the following procedures are scrupulously carried out: the preparation of the patient, the choice and implantation of the prosthesis, and the functional and psychological rehabilitation of the patient. PMID- 2099932 TI - Tibial osteotomy in the treatment of varus osteoarthritic knee. AB - Fifty-three patients treated between 1979 and 1986 with high tibial osteotomy for varus osteoarthritic knee are evaluated. The average follow-up was 6 years and 8 months (range 3-10 years). All of the osteotomies were stabilized using Weber's method. The purpose of the operation was to realign the mechanical axes with overcorrection of 3 degrees. Results were good in 71% of the patients, and 85% claimed to be satisfied with the operation. The preoperative varus, 9.5 degrees on average, was corrected to 2-degree valgus; the deformity was exactly corrected in 59% of the cases, undercorrected in 9%, and overcorrected in 32%. The corrections slowly deteriorated over time. The correlation between the results and the stage of the arthritis, the degree of deformity, and the alignment of the mechanical axes showed that the best results were obtained in monocompartmental lesions with a varus deformity of less than 10 degrees and in osteotomies resulting in an average postoperative mechanical axis of 184.5 degrees. Weber's method has undeniable advantages over other methods, such as stable internal fixation, rapid healing, early restoration of articular function and resumption of weight-bearing. PMID- 2099933 TI - Segmental femoral fractures: surgical strategies. AB - The authors identify six kinds of segmental femoral fractures. Such classification, however, does not simplify the problem of therapeutic approach. Since every fracture combination has its own unique characteristics, prearranged outlines of treatment are useless. A satisfactory surgical solution cannot be achieved without a general clinical evaluation. PMID- 2099934 TI - Arthroscopic lateral retinacular release of the alar ligament. Indications and long-term results. AB - The indications for and results of arthroscopic release of the lateral alar ligament are evaluated. This technique was used exclusively in cases of anterior patellar pain due to lateral hypertension resulting from disalignment of the extensor apparatus. It was used on 21 knees with a follow-up of 15-36 months. Excellent or good results were obtained in 85% of the cases, according to both subjective and objective evaluation. PMID- 2099935 TI - Degenerative arthritis of the adjacent spinal joints following anterior cervical spinal fusion: clinicoradiologic and statistical correlations. AB - On the premise that cervical intersomatic spinal fusion in the treatment of traumatic or spondylolytic myelopathy and post-traumatic instability provokes degenerative arthritis due to functional overloading of the spaces adjacent to the fusion, 37 patients (average age 57, range 25-80) who had undergone spinal fusion by Cloward's technique were subjected to radiographic study and clinical evaluation. The average follow-up was 11.5 years (range 7-16 years). In comparison with a control group of the same age who had not undergone this operation, these patients' C3-C4 and C6-C7 spaces (adjacent to the most commonly fused vertebrae) were smaller by 16.7% and 15.9%, respectively. In spite of the worsening of the radiographic situation, from a clinical standpoint there was a significant improvement in the symptomatology of 86.5% of the patients. Thus the degenerative arthritis is both less evident and, as far as the long-term clinical outcome is concerned, less influential than could be expected. This finding is confirmed by the lack of statistical correlation between the clinical results and the radiographic evidence. PMID- 2099936 TI - Mineral density of the os calcis in primary osteoarthritis of the hip and geriatric femoral neck fractures. AB - The calcaneal bone mineral density (BMD) was measured in 22 female patients operated on for femoral neck fractures on average 4.7 years ago, and 35 patients who had undergone total hip replacement for primary osteoarthritis on average 3.7 years ago, to test the hypothesis of an inverse relationship between bone density and osteoarthritis. After adjustment for the linear correlation between age and BMD, there was no significant difference between the groups with regard to BMD of the os calcis. PMID- 2099937 TI - The importance of urinary hydroxyproline and serumal osteocalcin in the evaluation of post-menopausal osteoporosis. AB - Forty-nine women aged 49 to 65 who had been in menopause for more than fifteen years were selected on the basis of densitometric data and clinical symptomatology. Twenty-four of these suffered from severe backaches and had a bone mineral content (B.M.C.) level inferior by at least three standard deviations to the average level according to the standards of our laboratory; these women were diagnosed with severe osteoporosis. The remaining twenty-five subjects were asymptomatic with a B.M.C. between one and two SD from the average; these were diagnosed with moderate asymptomatic osteopenia. A control group was formed by ten apparently healthy women of childbearing age. The women with severe osteoporosis showed a significantly lower level of serumal osteocalcin (Student t Test: P less than 0.05) than the control group, while no significant difference was observed between the latter and the women with moderate asymptomatic osteopenia. The level of hydroxyproline was significantly higher (Student t Test: P less than 0.01) in both groups of menopausal women than in the control group. This data shows that the increase in the level of urinary hydroxyproline characterizes menopause independent of the severity of bone loss. On the other hand, low levels of osteocalcin mainly appear in menopausal women who show severe skeletal demineralization. As a result, we feel that the urinary hydroxyproline/osteocalcin ratio is shown to be useful in both evaluating the risk of post-menopausal osteoporosis and monitoring it. PMID- 2099939 TI - [Auto-transplantation of small intestine, an emergency salvage procedure after failure of esophagoplasty]. AB - The colon or stomach is generally used for extended oesophagoplasty. These pediculated plasties may be complicated by necrosis or stenosis and require total or partial resection at a later stage. We report such an outcome in this case report: failure of left coloplasty, partial failure of right coloplasty and stomach then rendered unusable. The cervico-thoracic oesophagus was reconstructed using a free revascularised small bowel transplant, re-establishing the continuity between the cervical oesophagus and the retrosternal right colon. This case presents several particularities: semi-emergency salvage procedure, use of a saphenous vein graft to revascularise the intestinal artery using the lingual artery as nutrient artery, venous drainage of the transplant via the intrathoracic left brachiocephalic vein, necessity for resection of the left half of the manubrium sterni and the head of the left clavicle. PMID- 2099940 TI - [Value of investigation tests in thoracic goiters]. AB - Two groups of substernal goiters should be considered fist; the "simples" ones localised in the anterior and superior part of the mediastin. They are most common and less dangerous. By opposition to the "complexes" ones which have relation with the vessels, the airways and the digestive tube. That surgeons would like to approach with security. The study of those retrosternal goiters requires two categories of complementary examinations. One for diagnosis: X Ray standard of the neck and the chest; Echography Biopsy and Radioactive Iodine scintigraphy. Others for localisations to prevent the risks, particularly vascular seeing in the surgery of the substernal goiters: TDM and IRM. PMID- 2099938 TI - [Colonic cancers. A retrospective study of 1122 surgically-treated patients]. AB - A retrospective study of 1122 cancers of the colon operated by the same surgical team from 1973 to 1989 makes a number of statements possible: In spite of the improved diagnostic means, 66 (5.8%) only of the cancers were of Dukes' type A. 116 patients had complications, ie. perforation in 9 cases and obstruction in 107, among which 59 were operated within 24 hours. The rate of resection is very high: 93.8%. In 8.1% of all cases the excision was extended because of invasion of neighboring tissues. Curative resection was performed in 844 patients, while surgery was palliative in 278, including 205 excisions. The total operative mortality was 5.8%, sinking to 3.9% for curative surgery. It is as high as 22% in emergent surgery. Since 1981, it has been lower than 1% and only caused by general factors. The survival rate of 557 patients after more than 5 years is 46.6%. This rate was studied according to various parameters (sex, location, features of excision, Dukes' stage, involvement of lymph nodes). Lymph node involvement and Dukes' stage are the only factors having a significant influence on survival. In 90.0% of cases, the long-term death of patients followed up for more than 5 years is caused by hepatic metastases (66.6%), local recurrence (13.3%) or both (20%). The occurrence of local recurrence or hepatic metastases can sometimes be treated by second surgery, which has been performed in 20 patients: 11 hepatic resections with a 26.8% survival at 5 years, and 9 excisions for local recurrence with 12.4% survival at 5 years. PMID- 2099941 TI - [Prognosis of acute ischemia of the lower limbs in patients over 80 years of age. A prospective study]. AB - To demonstrate the importance of age in the prognosis of acute lower limb ischemia, a prospective study was performed in 137 patients over 24 months. Group I contained 75 patients aged under 80 years and group II 62 patients aged over 80 years. Risk factors and previous history were equally distributed in the two groups. The level of arterial blockage and the treatment were comparable in the two groups. Mortality was higher in group II than in group I (p less than 0.01). In both groups deaths were principally due to cardiac causes and a revascularisation syndrome. Amputation at thigh level was more common in group II (p less than 0.01). Mortality was higher in group II for combined thigh level amputation and cardiac or coronary insufficiency (p less than 0.05). This study demonstrated that, in terms of prognosis of acute lower limb ischemia, the critical threshold is 80 years. PMID- 2099943 TI - [Postoperative vascular infections. A pathognomonic x-ray computed tomographic sign]. AB - The potential gravity of post-operative vascular infection makes early diagnosis essential. We report a case where this diagnosis was made on CT findings alone, in the absence of any other signs of infection. Rapid intervention led to complete cure. Beyond the immediate post-operative period, the presence of gas on the CT scan is rare but pathognomonic in the absence of a cutaneous fistula. The presence of this sign is therefore sufficient to indicate that reintervention is mandatory. PMID- 2099942 TI - [Intestinal obstruction and pregnancy. Diagnostic and therapeutic approach. Apropos of 3 cases]. AB - The etiological diagnosis of obstruction is difficult during pregnancy. The authors report 3 cases of this rare association: obstruction due to adhesions [1], volvulus of the transverse colon on a common mesentery [1] and obstruction due to an appendix abscess [1]. Complementary investigations, obviously limited under these circumstances, were based on plain abdominal X-rays, repeated if necessary. The diagnosis must be made early and appropriate treatment given in order to ensure a good materno-fetal prognosis as was obtained in these 3 cases. PMID- 2099944 TI - [Villonodular synovitis. An uncommon localization: the ankle. Apropos of a case]. AB - The authors report an uncommon soft tissue tumor, a diffuse giant cell tumor of tendon sheath. The location is uncommon too, the ankle, behind tibial shaft and forward achilleus tendon. The primary diagnosis of ankle and leg lymphoedema, has been for a long time. But CT Scan and MRI allowing the discovery of a firm and multinodular mass, have permitted surgical excision and histological diagnosis. This case agrees with the literature review. The pigmented villonodular synovitis is rather uncommon in comparison to localized form. Young people and lower extremities are more affected; symptoms are of relatively long duration. Histological examination gives diagnosis but surgical excision has to remove the tumor completely as possible because of local recurrence rate of about 50%. PMID- 2099946 TI - [Percutaneous drainage of intra-abdominal collections. Conditions for success]. AB - Technological advances currently allow safe percutaneous puncture of certain intra-abdominal collections, provided the indications and technical precision are imperatively respected. Our aim is to draw attention to success factors and the limits of this procedure. PMID- 2099945 TI - [Synchronous bilateral cancer of the kidney in the adult. Apropos of a case]. AB - Following a case of synchronous bilateral renal cancer, we carried out a review of the literature and defined the specific therapeutic and prognostic characteristics of this clinical condition. Conservative surgery should be proposed as first line treatment. Results in terms of survival depend on the histological characteristics of the more affected kidney. The prognosis is relatively good in general and better than that of unilateral cancer. PMID- 2099947 TI - [Functional cervical lymph node excision with section of the sternocleidomastoid muscle]. AB - Based on 7 cases, the authors update the low section and subsequent suture technique of the sternocleidomastoid muscle in conservative cervical lymphadenectomy, principally for differentiated thyroid cancer. Due to the good exposure obtained, this technique permits functional clearance with excellent visualisation of the structures to be preserved and is associated with very minor functional sequelae. A review of the literature confirms the perfect feasability and reproducibility of this technique and justifies its use from a cosmetic viewpoint. PMID- 2099948 TI - [A small hospital ... for what use? Study og the surgical activity at the Loudon hospital 1989]. AB - General hospitals, even small ones, are by no means a secondary element in the French sanitary network, the authors analyze the activity of the department of surgery of Loudun Hospital to show that the part they play is far from negligible, with 1403 patients admitted within one year, 1071 surgical operations performed and 2719 patients received in the emergency unit. They ensure a highly appreciated physical and psychological comfort for the rural population. The costs of the stays are very competitive, even in comparison with private hospitals. These satisfactory sanitary conditions involve a particularly great devotion of both the medical personnel and the allied health workers. PMID- 2099949 TI - [Breast metastasis of ovarian cancer]. PMID- 2099950 TI - [Schwannoma of the rectum. Apropos of a case]. PMID- 2099952 TI - Epidemics in heterogeneous populations: II. Nonexponential incubation periods and variable infectiousness. AB - Two stochastic models for the spread of an infection through a heterogeneous population are considered. First, we consider a model where the incubation period has an increasing hazard rate but constant infectiousness; in the second model, the incubation period is the sum of p exponentially distributed stages, each with its own mean and level of infectiousness. By using multitype birth-death and branching processes as approximations to each epidemic model, it is shown that the epidemics initially have underlying exponential growth. Furthermore, the growth rate theta is an increasing function of the Frobenius root of the matrix of reproductive ratios R0. The results have applications in long-term sensitivity analyses, model fitting, and the determination of optimal vaccination strategies. PMID- 2099951 TI - [Mucinous cystadenoma of the pancreas. Apropos of a case]. PMID- 2099953 TI - The effect of couple stresses in squeeze film poro-elastic bearings with special reference to synovial joints. AB - In this paper, a theoretical study of squeeze film poro-elastic bearings with Stokes' couple stress fluid as lubricant is made. The analysis explains the working of poro-elastic bearings in general and describes the lubrication mechanism of synovial joints in particular. Compact closed form expressions for the fluid film pressure, load capacity, and approaching time as a function of film thickness during normal articulation of joints are obtained. It is observed that the bearings with couple stress fluid as lubricant provide significant load carrying capacity and ensure a delayed time of approach compared with viscous lubricants. The influence of elasticity is to increase the load capacity and yield a longer squeeze film time. A decrease in permeability of the bearing surface enhances the load capacity as well as the response time. This results in the efficient lubrication and proper functioning of synovial joints. PMID- 2099954 TI - Comparison of surgical modalities in the treatment of recurrent venous ulcer. AB - Recurrent leg ulcer secondary to superficial and deep venous valve incompetence that are refractory to non-surgical treatment can be healed with the following surgical modalities. Perforator ligation and saphenous vein stripping (PLSVS) healed 4/16 (25%) of the ulcer. PLSVS and correction of deep venous valve incompetence healed 14/16 (87.5%) of the ulcer (p less than 0.005). The mean follow-up was 32 months (8-62 mon). This prospective comparison of the 2 surgical treatments (PLSVS versus PLSVS and correction of deep venous valve) demonstrated that disassociation of the superficial from the deep venous system with PLSVS and correction of the deep valve (valvuloplasty, transposition or valve transplant) produced promising results in the treatment of recurrent venous ulcer. Adjunctive usage of elastic stocking and intermittent compression pneumatic boot to reduce swelling in the paraoperative period improved long term result in venous reconstructive surgery. PMID- 2099956 TI - Ruptured abdominal aortic aneurysms. Clinical and surgical considerations. AB - Rupture of abdominal aortic aneurysms (AAA) is a life-threatening condition and a leading cause of death in various countries. In spite of increased awareness of most physicians for an early diagnosis of the rupture, the performance of surgery in an early stage and special care in the Intensive Care Unit, postoperative mortality is still high in most medical centers as well as in our Clinic. Two series of patients operated in our Clinic during the last 17 years are analysed. The applied surgical technics are presented and morbidity and mortality are analysed. A distinction between the general mortality was made based on all the inhospital deaths and the postoperative mortality rate including only the deaths after the operation during the postoperative period. Among the other conclusions it is also stressed that a real improvement in the mortality rate depends on elective surgery of all the disclosed AAA larger than 4 cm in diameter. PMID- 2099955 TI - Surgical treatment of venous insufficiency. AB - The incidence of venous insufficiency syndrome (VIS) is increasing. Although clinical findings will help for diagnosis of this condition, invasive and non invasive tests confirm the diagnosis. Thermodilution, a new and unique technique, appears to be the only test for diagnosis and decision making for treatment of this condition. Overloading and increase muscle work appear to be present in cases of VIS. Cases of failed medical treatment and findings of increased flow, with venography evidence of grade IV venous insufficiency are generally subjected to surgical treatment. Ninety-four cases of severe VIS have been operated on since July 1980 with 75% excellent results. PMID- 2099957 TI - Evaluation of non-invasive haemodynamic parameters in patients with intermittent claudication subjected to physical training. AB - In a group of 26 patients, all smokers (mean age 56.9 +/- 8 years), with intermittent claudication due to arterial obliterative disease. We investigated some of the haemodynamic, haematologic and clinical parameters before and after a 3 months physical training program. During the training period, none of the patients were given vasoactive, anticoagulant, antiaggregant or other drugs which could affect blood lipid. Patients were instructed to walk for a minimum period of 1 hour daily, in addition to normal everyday activities. Statistically significant differences of claudication pain distance were obtained: 177 +/- 88 m vs 107 +/- 40 m, +65% (p less than 0.001); maximal walking distance: 456 +/- 205 m vs 250 +/- 138 m, +82% (p less than 0.0001) determined during treadmill test at 2 mph up 12% and t/2 peak flow: 30 +/- 11.6 sec vs 46.3 +/- 32.3 sec (p less than 0.02), determinated with plethysmographic venous occlusion strain-gauges studies. An important, but not significant decrease of fibrinogen was obtained: 302 +/- 60 mg% vs 328 +/- 57 (p = 0.06), whereas no statistically significant differences were found for the more important haemodynamic parameters: (1) Widsor index determinated before (60 +/- 14% vs 58 +/- 15%) and after (26 +/- 17% vs 26 +/- 17%) treadmill-test with Doppler ultrasound; (2) peak-flow (10.5 +/- 2 ml/100/min vs 10.2 +/- 3); (3) time to peak-flow (17 +/- 10.5 sec vs 19.3 +/- 12.1). We also didn't find any significant differences in total cholesterol (227 +/- 53 mg% vs 228 +/- 48) and haematocrit (43.6 +/- 3.5% vs 43.5 +/- 3.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099958 TI - Relationship between serum cholesterol and thromboxane B2 levels and atherosclerotic lesions in rabbits fed a high cholesterol diet. AB - The aim of our study was to evaluate the effects of diet induced hypercholesterolemia and associated atherosclerosis in rabbits on serum thromboxane B2 levels. We have determined thromboxane B2 in serum of hypercholesterolemic rabbits with atherosclerosis and in normocholesterolemic rabbits without atherosclerosis. Our data show only a mildly higher serum thromboxane levels in hypercholesterolemic rabbits and extensive atherosclerosis than in controls without atherosclerosis. In conclusion, these results show that diet induced hypercholesterolemia was not associated with thromboxane B2 generation, in spite of a diffuse experimental atheromatosis. PMID- 2099959 TI - Transcutaneous oxygen pressure and hemorheology in diabetes mellitus. AB - Diabetes is associated with altered blood viscosity and abnormal tissue oxygenation. Transcutaneous oxygen tension is measured in 119 diabetic and 20 normal subjects. Measurements of transcutaneous oxygen pressure (TcPO2) are made by Oxymonitor SM 361 at 45 degrees C at the dorsum of the foot. At the same time, the main microrheological parameters (plasma viscosity, albumin, fibrinogen, red cell aggregation times, disaggregation threshold and red cell aggregate structure index) are measured in diabetic patients with good and poor glycemic control, with and without angiopathy. All the diabetics have a significant reduction of TcPO2 and have rheological disturbances. TcPO2 values are related significantly with plasma viscosity and with several parameters of aggregation-disaggregation phenomenon. As for microrheological parameter abnormalities, it seems that tissue hypoxia precedes clinical signs of angiopathy and depends on the metabolic state as rheological abnormalities. TcPO2 values are the result of numerous parameters as rheological parameters. It seems that TcPO2 measurement is able to provide useful informations about microcirculation in diabetes mellitus without clinical signs of tissue hypoxia. PMID- 2099960 TI - Progression of induced aortic atherosclerosis in rabbits fed a high cholesterol diet. AB - In this study we have evaluated the progression of atheromatosis in aortic arch, thoracic aorta and abdominal aorta in rabbits fed a high cholesterol diet. The aortic atheromatosis decreased progressively from the aortic arch to the abdominal aorta after 6 months of high cholesterol diet. It is possible that a different segmental resistance to hypercholesterolemic damage may be involved in the cranio caudal progression of atheromatosis in rabbits. PMID- 2099961 TI - Combined intravenous and oral pentoxifylline in the treatment of peripheral vascular disease. A clinical trial. AB - Sixteen patients with severe occlusive vascular disease of the lower extremities were randomised to receive a five day course of combined intravenous and oral Pentoxifylline followed by three months oral treatment only, or identical treatment with a matching placebo. Nine patients received active Pentoxifylline, and 7 placebo, Follow-up by regular clinical examination and haemoreological assessment revealed a marked improvement in claudication distance and an increase in red cell deformability in those receiving Pentoxifylline, there being no change in those receiving placebo. Although both of the above parameters were improved by the treatment, there did not appear to be a direct correlation between red cell deformability and claudication distance in individual patients. A combination of intravenous and oral Pentoxifylline therapy results in an increase in both claudication distance and red cell deformability, but the former may not te a direct consequence of the latter. PMID- 2099963 TI - Effects of defibrotide after oral and parenteral administration in patients with peripheral obliterative arterial disease (POAD). AB - Defibrotide (D) a polidesoxyribonucleotidic derivative provided with fibrinolytic and antithrombotic activity has already proven effective when administered by parenteral route in patients with peripheral obliterative arterial disease (POAD). Bioavailability studies gave evidence that the drug is absorbed by 50-70% when administered orally. Thus, aim of this trial was to evaluate whether the drug might exert similar clinical and biological effects after oral/parenteral dosing in a 2:1 ratio. This was a randomized cross-over study including 17 out patients with POAD (Leriche stage II). D was administered by oral (400 mg b.i.d.) and intramuscular route (200 mg b.i.d.), both treatments lasting 15 days. In basal conditions and at the end of both treatments the following evaluations were made: (1) absolute walking distance (tread mill); (2) Doppler ultrasonographic examination (Winsor index); (3) strain-gauge plethysmography (rest flow and peak flow). In addition in the same occasions plasma samples were collected for the assessment of plasminogen (chromogenic assay) and fibrinolytic activity (fibrin plates). Defibrotide administration was followed by a significant increase in walking distance both after oral and parenteral administration [basal conditions (IRL): 232.7 +/- 23.0 meters; oral: 273.1 +/- 28.1 m; i.m.: 277.9 +/- 26.8 m, p less than 0.01 - (IRA) basal conditions: 380.1 +/- 25.6; oral: 437.1 +/- 31.5 m; i.m.: 442.5 +/- 34.0 m, p less than 0.01] and by a significant increase in peak flow (basal conditions: 9.66 +/- 1.04; oral: 10.90 +/- 0.90; i.m.: 11.12 +/- 0.98, p less than 0.05), while Winsor index and rest flow were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099962 TI - The prevalence of peripheral vascular disease in sulfonylurea treated diabetic patients with proteinuria. AB - The aim of this study was to assess the prevalence and the possible risk-factors for the development of peripheral vascular disease (PVD) in sulfonylurea-treated diabetic patients with proteinuria. Fifty non-insulin-dependent diabetics (NIDDs) with proteinuria (greater than 500 mg/24 h), with age less than or equal to 75 years and duration of diabetes greater than or equal to 5 years, and forty-eight NIDDs without proteinuria, matched for age, sex, body mass index (BMI), duration of diabetes and glycaemic control, were studied using Doppler ultrasound. Risk factors analysed included smoking, hypertension and metabolic indices (cholesterol, HDL-C, triglycerides). The prevalence of PVD was 44% in the proteinuric disease group compared to 14.6% in those without proteinuria (p less than 0.01). Among the risk factors analysed, hypertension and triglyceride concentration were significantly higher in the proteinuric diabetics (p less than 0.01), while HDL-C levels were found to be significantly lower in this group (p less than 0.05). We conclude that the prevalence of PVD was significantly higher in NIDDs with proteinuria. Furthermore, proteinuric patients had higher blood pressure and low HDL-C. PMID- 2099965 TI - Are low levels of HDL2-cholesterol a risk factor for atherosclerosis of cerebral vascular disease? Case report. AB - A case of a 45 years old man with an atherosclerotic stenosis of right internal carotid and TIA event is reported. The patient showed an increase of total cholesterol and LDL-cholesterol serum levels and, in particular, a very low familiar HDL2-cholesterol serum value. The possibility that this last condition could represent an important co-factor of the extracranial cerebrovascular disease is discussed. The usefulness of a long-term follow-up of all family members, showing the same lipids pattern, is also suggested. PMID- 2099964 TI - Primary aorto-enteric fistula: a practicable curable condition? Pathogenetic and clinical aspects. AB - Primary aorto-enteric fistulas is now being a rare occurrence because of an aggressive approach in terms of surgery of abdominal aortic aneurysms. Three cases is presented in an attempt to elucidate the ethiology, pathogenesis and diagnostic possibilities when dealing with primary aorto-enteric fistulas. The clinical presentation of the patients with primary aorto-enteric fistulas is inconstant, but a hightened index of suspicion should be present when a patient presents with gastrointestinal bleeding of obscure origin, abdominal or back pain and an abdominal mass. Endoscopy and diagnostic imaging may detect a fistula, but a high rate of false negative investigations are produced. The result of diagnostic workup is often laparotomy, which is the safest diagnostic method and may save the patients life. PMID- 2099966 TI - Simultaneous mesenteric and renal bypass for visceral ischemia and renovascular hypertension. AB - Severe visceral ischemia and uncontrollable hypertension in a patient with previous aortofemoral and right aortorenal bypasses underwent surgical correction for stenosis of the celiac, superior mesenteric and left renal arteries. A Dacron jump graft from the junction of the aorto-celiac trunk to the superior mesenteric artery artery alleviated the mesenteric ischemia. A nonreversed vein graft connected the side of the Dacron prosthesis to the end of the left renal artery improved the renovascular hypertension. This modified, simple surgical approach, successfully corrected visceral ischemia and renovascular hypertension and avoided using the severely calcified aorta for celiac and mesenteric bypasses. PMID- 2099967 TI - Successful treatment of an impressive primary lymphedema of the extremities. AB - We report the case of an impressive primary lymphedema of the four extremities which did not response to previous conservative and partial surgical treatments and imposed the amputation of both the lower extremities and of the left arm. We have successfully treated the involved right arm by means of radical excisional procedure and skin graft. After five years no recurrence of the disease was observed and morphologic and functional recovery is complete. PMID- 2099968 TI - Atherosclerotic aortic-bisiliac aneurysms in two monocorial twins. AB - Two cases of aorto-bisiliac aneurysms in monocorial twins in their sixties were observed. We report experimental and clinical data from the literature about genetic involvement in the formation of aneurysms, especially when associated with other risk factors. In addition to the genetic factors in the twins we studied, we also found other risk factors, such as hypertension and smoking, which took a long time to affect the patients before the aneurysms were detected. PMID- 2099970 TI - Evaluation of a pulse oximeter during profound hypothermia. An assessment of the Biox 3700 during induction of hypothermia before cardiac surgery in paediatric patients. AB - The accuracy of the Ohmeda Biox 3700 pulse oximeter was evaluated in 10 paediatric patients, deliberately surface cooled to 25 degrees C in preparation for cardiac surgery, by comparing the arterial oxygen saturation results obtained from an Ohmeda Biox 3700 and a Radiometer OSM-2 Hemoximeter. Though there was a good correlation between the two series of results, the arterial oxygen saturation was over-estimated by the pulse oximeter compared to the OSM-2 Hemoximeter in the temperature range 36 degrees to 30 degrees C and under estimated below 30 degrees C. These differences were greatest when the initial saturations were low. PMID- 2099969 TI - Probability and the patient state space. AB - This paper describes work to develop a model-based system to support clinical decision-making. In previous articles, we have developed (from 695 measurement sets obtained from 148 patients) a physiologic state classification based on a set of 11 cardiovascular and metabolic measurements. There is an R or reference state, for stable ICU patients. Patients under (operative, traumatic, or compensated septic) stress, or with (septic or hepatic) metabolic, respiratory, or cardiac insufficiency are in the A, B, C, or D states, respectively. We wished to make the state easier to measure and eventually available continuously, automatically, and noninvasively, as well as reflecting a wider group of bodily systems. The 5 centers define a 4 dimensional affine subspace, designated the cardiovascular state space. Using eigenvector analysis, we have found four new derived physiologic variables CV1, CV2, CV3, and CV4 that span the state space. We have fit sets of linear regression equations that allow the patient's position in the state space, and therefore his state, to be determined from more easily obtainable sets of measurements. Further, we selected 1966 measurement sets from 512 patients at two hospitals. We used the data from 250 of these patients to define 13 prototypical types, namely survivors and deaths from various combinations of sepsis, cardiogenic decompensation, cirrhosis, and pneumonitis, following trauma or general surgery. For any future patient, the statistical theory of Bayesian inference allows one to infer back from the measurements observed to the probability of his being of any of these types and of surviving or dying. We used this method to predict the outcome of the other 262 patients, prospectively. Statistically, the predictions of survival or death were not significantly different from the actual. For individual patients, the method predicts a clinical course that closely follows the actual episodes in their history. These results confirm and explain the validity of the concept of the patient state and make the state easier to compute. The patient state and the probability plot together help to stage, select, and evaluate therapy. They do not replace the clinician's judgement, but rather are tools that help the clinician to exercise judgement. PMID- 2099971 TI - A system for ambulatory monitoring and computerised analysis of oesophageal motility and luminal pH. AB - It is often desirable to monitor physiological events from subjects free to participate in their normal daily activities. This is especially so where clinical symptoms are elusive or precipitated by specific activities. Through ambulatory monitoring, evidence of a causal relationship between recorded parameters and the spontaneous onset of symptoms may be revealed. We describe an ambulatory monitoring system which permits continuous 24-hour recording of oesophageal motility from three levels within the oesophagus together with luminal pH. Computerised analysis of the recorded data addresses many of the problems associated with processing the information accrued through long-term monitoring by providing an automatic comparison of patient data against either preselected values or those of the program's algorithm. Motility is quantified in terms of wave frequency, amplitude, duration and temporal relationship together with an integration of the wave area and mean pressure baseline. The corresponding pH data is quantified as frequency, duration and integrated area of pH excursions throughout a range of pH1-8. This system provides access to the entire patient record which may either be viewed on screen, analysed or output to a printer. Analysis yields a tabulated breakdown of motility and pH events from any section of the patient's record. Selective analysis readily permits statistical comparison of discrete time-matched samples corresponding to different patient circumstances. PMID- 2099972 TI - A patient monitoring system designed as a platform for application development. AB - This paper presents a patient data monitoring system for use in critical care areas. The system incorporates design criteria from the Institute of Electrical and Electronic Engineers' (IEEE) proposed standards body (P1073), the Medical Information Bus (MIB) and from our design team. Existing hardware and software technology is utilized wherever possible to maintain cost effectiveness. A major design objective is providing a consistent environment in which to develop applications for critical patient care delivery. The system allows applications to be developed without specific knowledge of the configuration of the bedside environment. Therefore, investments in 'user' application development are shielded from changes in patient care delivery technology. The system has been in limited operation in a surgical intensive care unit for several months with prototype applications. PMID- 2099973 TI - Monitoring regional anaesthesia. AB - Monitoring patients under regional anaesthesia is more challenging than patients under general anaesthesia but it has been somewhat neglected in anaesthesia literature. The fundamental differences are that during regional anaesthesia. 1. The patient is often awake. 2. Respiration is more difficult to measure. 3. Autonomic changes influence information obtained by pulse oximetry. 4. Monitoring personnel are at a greater risk of vigilance decrement. A review of reported complications during regional anaesthesia enabled conclusions to be reached regarding monitoring policies in an institution. These include particular reference to spontaneous respiration and cerebral function. The need for an appropriately skilled person monitoring the patient in the operating room at all times is emphasized, as is the necessity for education appropriate for the skills they may have to exercise even on rare occasions. Specific instruction in vigilance decrement avoidance should be part of that curriculum. PMID- 2099974 TI - Universities and the clinical monitoring industry: feckless independents or fruitful partners? AB - Since 1955 clinical monitoring in anesthesia care and critical care has improved markedly. However, both industry and academia find temptation to congratulate themselves on this achievement. Reflection, however, might suggest that, in comparison with analogous unrelated fields, the process of progress has been tardy, wasteful, expensive, and inefficient. 'State of the art' clinical monitoring may actually be viewed as woefully inadequate when measured by the yardstick of the possible. Analysis suggests that industry sometimes fails to grasp opportunities for progress by shared effort while academia, sometimes guilty of aloofness and isolation, may occasionally fail to cooperate actively to promote progress by sharing its experience with industry. To hasten the more efficient development of clinical monitoring by a new alliance of the clinical monitoring and computing industry and those universities, professors, and physicians with interests in clinical monitoring and computing is here proposed. A Foundation for Research, Development, and Advancement of Clinical Monitoring and Computing Devices should be established, to promote basic and practical research and development (R&D), sponsor shared specialized clinical testing facilities, special scholarships for physicians training as specialists in development of clinical monitoring devices, and promote and expand continuing medical education programs. By this multidisciplinary, cooperative activity, it is asserted that progress in the introduction of useful new clinical monitoring devices can be accelerated. PMID- 2099975 TI - Automated anesthesia surgery medical record system. AB - Manual recording of physiological data in patients receiving anesthesia or intensive care infrequently meets medical requirements or legal documentation standards. Automated recording allows the generation of reliable data that can be integrated into the patient's medical record. Such a system is beginning to function at University Hospital at Stony Brook, New York. Bedside medical devices (pulse oximeters, non-invasive blood pressure monitors, capnographs, infusion pumps and physiological monitors) from 18 operating rooms and 16 beds in the Anesthesia Intensive Care Unit are connected to a baseband Ethernet system. Data from the above devices are stored in a MicroVAX computer system. Data compression and interpretation, computation of derived values, statistical analysis of data from two related parameters are done by the bedside graphical microcomputer workstation. The MicroVAX computer and the workstation are also connected to the Ethernet system. The overall architecture of the automatic record system conforms to emerging standards for information exchange between bedside monitors and computer systems. Health care recipients and providers are likely to reap the benefits. PMID- 2099976 TI - [Corticosteroids]. AB - Adrenal steroids, particularly glucocorticoids, are used in a variety of conditions ranging from adrenal insufficiency requiring substitution therapy (glucocorticoids and mineral-corticoids), to a wide range of clinical disorders in which undesired inflammatory reactions must be reduced (glucocorticoids). The anti-inflammatory effect, typical of glucocorticoids, is mainly due to the interference with arachidonic acid metabolism, from which both prostaglandins and leukotriens, mediators of inflammation, take origin. ACTH is also employed with the same indications of glucocorticoids, but its use is limited, since its effect depends on the stimulation of cortico-adrenal gland with subsequent release of not only glucocorticoids but also mineral-corticoids and androgens. The therapeutical indications of glucocorticoids are numerous, but dose and duration of treatment vary in relation of the disease that is to be cured. The widespread use of steroids is accompanied by numerous unwanted reactions which depend on their metabolic actions. Therefore corticosteroids must be reserved to well defined clinical conditions and their use should be guided by criteria that are now codified. In this review the physiological and pharmacological effects and the clinical use of corticosteroids have been examined. PMID- 2099977 TI - [Adverse effects of corticosteroids]. AB - Due to their anti-inflammatory and immunosuppressive properties, as well as their action on the hematopoietic system and the calcium phosphate turnover, corticosteroids are widely employed in the treatment of many diseases. However, the therapeutic use of these compounds is frequently associated with unwanted, mainly type A, effects that are directly dependent on the wide spectrum of their pharmacological activities. In this study these side effects are critically reviewed and classified on the basis of the organs and systems involved. Where possible, the incidence, pathogenesis, type of steroid, dose and schedule are reported, and the precautions that should prove useful in reducing the incidence and gravity of the side effects are given. PMID- 2099979 TI - [Intraoperative echoencephalography in neurosurgery]. AB - Intraoperative ultrasonography with real time sonographic imaging equipment is widely used and, in the neurosurgical operating room, has been really successful, initially in the brain and subsequently in the spinal cord as well. Its main applications i.e. accurate needle biopsies, localization of intracerebral masses, placement of ventricular and cyst shunts, can diminish the amount of potential damage to normal brain tissue. Moreover results of tumor resection may be intraoperatively confirmed and the end results are more accurate. No intraoperative complications and no postoperative infections result from use of ultrasound in the operating room. No evidence is given that the small amount of mechanical vibration emitted by the transducer damages the brain or the spinal cord. Surgical procedures, as a result, are faster, safer and better planned by virtue of informations obtained by ultrasonographic intraoperative examination, instead of simple preoperative imaging procedures. PMID- 2099978 TI - [Infective endocarditis: a changing disease]. AB - Infective endocarditis is best characterized as a disease in evolution. The list of patients at risk, which formerly included almost exclusively patients with rheumatic heart disease, is being continuously modified and expanded. Nowadays, patients with prosthetic heart valves, users of illicit intravenous drugs, and patients with mitral valve prolapse rather than patients with rheumatic heart disease account for the majority of cases of infective endocarditis. Moreover, due to the widespread use of indwelling atrial catheters for parenteral nutrition as well as for intensive cytotoxic therapy, catheter-related right-sided endocarditis is emerging among nosocomial infections. With the advent of successful antimicrobial therapy, complications rather than endocardial infection pose the major therapeutic problems. In addition to progressive heart failure, myocardial abscesses, fungal endocarditis, relapsing infection, and major systemic emboli in the presence of large protuberant vegetations constitute indications for replacement of the valve. Despite progresses in diagnosis and therapy, infective endocarditis will most likely continue to challenge physicians even in the next future. PMID- 2099980 TI - [Hirudin inhibition of human thrombin activity]. AB - Thermodynamics and kinetics for hirudin binding to human alpha-, beta- and gamma thrombin, under experimental conditions which mimic the in vivo conditions (i.e., pH = 7.35, T = 37.0 degrees C, I = 0.1 M), indicate that the inhibitor specificity for the three species of the enzyme is different. Such a finding agrees with the human thrombin:hirudin binding geometry as revealed by X-ray crystal studies. From the therapeutic viewpoint, thermodynamics and kinetics here reported indicate that the inhibitory activity of hirudin in vivo is more effective than that shown by antithrombin III, which is generally considered the most important plasma thrombin inhibitor. PMID- 2099981 TI - [Macrophages from healthy adults release TNF-alpha after exposure to Pneumocystis carinii of murine origin. Preliminary study]. AB - The ability of Pneumocystis carinii to induce TNF-alpha release by macrophages from adult healthy humans was investigated. Monocytes and monocytes derived macrophages produced an high amount of TNF-alpha when exposed to P. carinii cysts obtained from rats with steroid induced pneumocystosis. TNF-alpha release was P. carinii specific as shown by the inhibition exerted by the anti-P. carinii hyperimmune serum and it was not mediated by putative traces of endotoxin. PMID- 2099982 TI - [Prevalence and clinical meaning of insulin-specific IgE antibodies]. AB - Systemic and local reactions to insulins in patients affected by insulin dependent diabetes are uncommon but may be life threatening. Both systemic and local adverse reactions to therapy may be managed by different therapeutic schemes. The availability of human (DNA recombinant) insulin raised hopes that this be the choice treatment for allergic complications. However, controlled studies showed that reaginic (IgE) antibodies are directed to common insulin determinants and not to heterologus protein contaminants. Therefore we investigated in 62 patients undergoing insulin therapy, prevalence and clinical significance of the detection of specific IgE to insulin. Furthermore, we searched for a relationship between atopic status and the presence of antiinsulin IgE. In our study prevalence of specific IgE to insulin was 16.1%. We showed a correlation between clinical symptoms and the presence of specific IgE to insulin, when these antibodies are of an elevated class (R.A.S.T. class 2 or more). When specific IgE were present we detected antibodies to all insulines (bovine, porcine and human) thus confirming that specific IgE are directed to a common antigenic determinant. Finally, we couldn't find a relationship between atopic status and the presence of reaginic antibodies to insulin. PMID- 2099983 TI - [Clinical manifestations correlated with anticardiolipin antibodies in systemic lupus erythematosus: preliminary results of a prospective study]. AB - Antiphospholipid antibodies (aPL) have been linked to various clinical manifestations in systemic lupus erythematosus (SLE), mainly thrombosis, repeated abortions and thrombocytopenia. Despite the large number of studies which have been published in the recent years, there is still some debate on this matter, and no firm conclusion has been reached as yet. Among the various aPL, anticardiolipin antibodies (aCL) have received more attention, mostly because they can be easily detected by means of immunoenzymatic assays. The main objective of the present study was to determine the prevalence of IgG and IgM aCL isotypes in SLE in order to compare their possible association with the clinical manifestations of the disease. Clinical features of 40 consecutive and unselected SLE patients (35 female and 5 male) were prospectively studied. Sera from the same patients were tested for the presence of aCL, using a standardised ELISA assay, and the presence of aCL was correlated with the various clinical events. Results showed that the prevalence of aCL was 42.5% for the IgG isotype and 10% for the IgM isotype. Regarding the clinical associations of aCL, we found a strong linkage between the presence of these antibodies and the occurrence of both thrombosis and abortions; a weaker association with neurological events was also demonstrated. These results, if confirmed on larger series, suggest that aCL should be searched in patients with SLE in order to identify those who are at greater risk of developing some severe clinical problems and could benefit by prophylactic treatment. PMID- 2099984 TI - [Prognostic factors in Raynaud's phenomenon: usefulness of antinuclear antibodies and of periungual capillaroscopy]. AB - Antinuclear antibodies (ANA) and nailfold capillary microscopy have been evaluated as prognostic markers in patients with apparently idiopathic Raynaud's phenomenon. Results have shown that either ANA and peculiar alterations in nailfold capillaries are important risk factors as regard to the evolution into a connective tissue disease; furthermore, when both these markers are present in a patient with Raynaud's phenomenon, the risk of evolution is even greater. When sensibility and specificity have been compared, ANA appeared to be a more sensible test but nailfold capillary microscopy seemed to be more specific. Our data suggest that ANA and capillary microscopy are important tests in patients with Raynaud's phenomenon; they should be performed in order to identify those patients who are at greater risk of evolving to overt connective tissue disease. PMID- 2099985 TI - [Skin disease in Basedow's disease]. AB - Two cases of Graves' (Basedow) dermopathy are reported. In one case pretibial myxoedema was localized on the external surface of the legs down to insteps. In the second case a diffuse form involved both legs and was characterized by wrinkles and peau d'orange appearance at the ankles. In both cases a biopsy confirmed the diagnosis of Graves' dermopathy, showing diffuse areas of amorphus substance infiltrating the derma and fragmentation of collagen fibers. According to the literature, the skin lesions were associated with ophtalmopathy. Thyrostatic therapy affected ophtalmopathy in one of the patients, while pretibial myxoedema regressed in both. The pathogenesis of pretibial myxoedema is not completely clear yet, although dermopathy, along with ophtalmopathy and acropachy, is considered to be an extrathyroidal manifestation of Graves' disease related to bioassayble antibodies anti-TSH receptor. A class of dermopathy associated antibodies (DAAb) has been identified. It seems to be a reliable biological marker for pretibial myxoedema since it is nearly absent in patients with ophtalmopathy and without dermopathy. Since DAAb does not stimulate human fibroblasts in culture, the role of DAAb in the development of Graves' dermopathy is still to be found. PMID- 2099986 TI - [Clinical usefulness of a new echocardiographic window: the transesophageal approach]. AB - The image quality of standard echocardiograms can be unsatisfactory for various reasons such as pulmonary disease, obesity, chest deformities. The introduction of transesophageal echocardiography has solved these problems and provided a new acoustic window to the heart and mediastinum. Its superior imaging resolution and increased sensitivity allow cardiac structure and function to be visualized in great detail. The procedure has proven to be a valuable means of intraoperative and perioperative monitoring of left ventricular performance and in the evaluation of surgical results. In critically ill patients, diagnoses missed at surface echocardiography, including aortic dissection, left atrial masses, native or prosthetic valve vegetations, have clearly been identified by transesophageal window. In awake patients, the procedure is well accepted and associated with no major complications. On the basis of our initial experience, we conclude that esophageal approach complements standard two-dimensional, Doppler, and color flow examinations, and is a major advance in the care of patients with cardiovascular disease. PMID- 2099987 TI - [Decrease in notifications of AIDS dementia complex in 1989-1990 in Italy: possible role of the early treatment with zidovudine]. AB - We evaluated the incidence of AIDS dementia complex (ADC) in groups of patients who acquired infection through different risk behaviours, and attempted to evaluate the possible role of zidovudine (AZT) treatment in preventing or delaying the onset of ADC. The Italian National AIDS Registry was used to study patients with AIDS for whom ADC was reported as an index disease. Relative risk of presenting ADC between different patient categories has been determined. Logistic regression was used to analyse temporal trends in the proportion of AIDS cases presenting with ADC. Of the 6466 cases reported between August '87 and August '90, ADC was seen in 640 (9.9%). I. V. drug addicts had twice the risk (estimated odds ratio: 1.9; 95% confidence interval: 1.5-2.6, p less than 0.001), compared to homo/bisexuals, of presenting with ADC. There is significant evidence (p less than 0.0001) that after a progressive increase in the period '87-'89, it began a definite decrease in the monthly proportion of ADC cases, starting August '89. AZT was introduced in Italy in July 1987 for patients with AIDS or advanced ARC. The incidence of AIDS dementia complex at the moment of AIDS diagnosis in our population of patients, began to decline 24 months after the introduction of systematic AZT treatment in Italy. This could have been due to inhibition of HIV replication in the Central Nervous System among patients who initiated AZT treatment before developing full-blown AIDS. PMID- 2099988 TI - [The human genome project: reflections of an expert]. AB - Just about five years have elapsed since a handful of leading scientists began to discuss the opportunity to launch the Human Genoma Program, an international organized effort to characterise all the genetic material--DNA--of the human organism. Today, the project is well under way with the participation of tens of thousands investigators from all over the world and the direct involvement of major sponsoring bodies such as the United States Department of Energy and the National Institutes of Health, the European Economic Council, the USSR Academy of Sciences and the Governments of France, Great Britain, Italy, Japan and Spain. Yet, the reactions of the general public to the Project is, to say the least, very diverse. Some are sure of its positive impact on the prevention and cure of inherited diseases, some fear its infringence on individual privacy, but the majority remains totally indifferent. Since the lack of adequate information is the common denominator at the root such different reactions, this Editorial will try to summarise the major issues of the Project and their impact on Society.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2099989 TI - [Infectious diseases]. PMID- 2099990 TI - [Cardiovascular response to the cold test in obese subjects. Effect of a hypocaloric, normal sodium diet]. AB - Loss of weight in obese patients, both hypertensive and normotensive, causes a fall in blood pressure (BP) through a mechanism which is still not fully understood. The effects of a low-sodium low-energy diet on BP were assessed in 20 obese subjects (15 M and 5 F; age 26-65 years), 11 of whom were normotensive and 9 hypertensive. Following a period of normocaloric diet, a diet of 600 kcal was prescribed for 6 months. BP and heart rate (HR) were measured at the start and end of hypocaloric diet in resting conditions and during stimulation of the adrenergic nervous system (ANS) obtained by exposure to cold (immersion of the hand in water and ice). A reduction of resting BP (from 137/81 +/- 5/4 to 122/74 +/- 4/4 mmHg, p less than 0.05) was observed in 8 patients who lost at least 30% of excess weight (from kg 107 +/- 6 to 91 +/- 4, p less than 0.001) together with an increase in BP during exposure to cold (from 140/82 +/- 3/3 to 156/95 +/- 7/4 mmHg before and from 120/78 +/- 3/4 to 140/88 +/- 3/3 after the diet, p less than 0.05). No changes were found in the daily urinary excretion of Na during the course of diet therapy. These results demonstrate that a hypocaloric diet, independent of saline restriction, is able to reduce resting BP and pressure peaks during adrenergic stimulation. PMID- 2099991 TI - [A new proposal for nutritional education in a group of obese adolescents]. AB - A new "active" system of monitoring and dietary education was experimented in a group of 20 obese adolescents waiting to start diet therapy. Each subject was requested to record all food and drink consumed during two separate periods, each lasting 7 days, at a distance of 15 days from each other, at home using an optic reader and book of bar codes. On the basis of answers to a questionnaire which was completed at the beginning and end of the study, aimed at assessing the level of knowledge of basic food hygiene, the majority of participants considered the experience useful and amusing and were willing to repeat it; in addition, a greater knowledge of nutritional principles and of the rations consumed was shown at the end of the study. The results of the study were analysed using the Food Meter-Miles computerised system and showed daily calorie intakes of 1514 +/- 524.0, M +/- DS (protein 18.3 +/- 5.1%, lipids 33.7 +/- 6.2%, glucose 47.9 +/- 8.6%, total fibre 14.4 +/- 4.6 g) in female subjects, and 2096.1 +/- 80.8 (protein 16.1 +/- 3.6%, lipids 38.2 +/- 2.9%, glucose 45.7 +/- 3.9%, total fibre 18.1 +/- 2.0 g) in male subjects. The number of foods chosen was very low considering the range of foods available (277) and the length of time studied: 35.7 +/- 11.8 and 35.0 +/- 6.0 respectively for female and male subjects. With regard to the number and type of meals eaten, a high number of snacks was observed which supplemented or replaced main meals. PMID- 2099992 TI - [Statistical techniques for developing equations for impedance measurement]. AB - The use of impedance analysis is becoming increasingly widespread as a safe, non invasive and quick method to assess body composition. Numerous equations, based on variables derived from anthropometric variables as well as from impedance measurements analysis, have been developed to predict the alipidic mass from the resulting analysis. The most frequently used statistical method is the least squares technique. The inadequate reliability of this statistical technique is examined in this study and the use of the technique known as "ridge regression" is suggested. PMID- 2099993 TI - [Relationship between eating behavior and distribution of body fat]. AB - In these recent few years the study of the pathogenesis of obesity include the observation of the difference in eating behaviour between obese and non obese subjects. Therefore, current therapies now take into account, among others, also a program of behavioural therapy. On the other hand, recent studies have revealed the role of different body fat distribution on the obesity prognosis, especially considering cardiovascular risk factors. To this purpose much attention has been focused on the measurement of waist and hips circumferences and their ratio (WHR) considered important predictors of risk associated with obesity. Aim of this study was the observation of some differences in eating habits and psychological status during a 24-hr period in relationship with the android or gynecoid type of obesity. 102 outpatients were divided in two groups: 1) with WHR less than 0.85; 2) with WHR greater than or equal to 0.85. All subjects were given a questionnaire in which by a scale from 0 to 3 they expressed their appetite sensation during different hours of the day. In addition, they indicated their motivation to loose body weight. Our results demonstrated that subjects with WHR greater than or equal to 0.85 showed higher appetite sensation, during the whole day, with a peak at lunch, in comparison with subjects with WHR less than 0.85. Subjects with gynecoid type of obesity seemed to pay much attention to their body image than subjects with android type of obesity and complained less physical disorders than subjects of the second group. These preliminary data seem to suggest a non-secondary role of behavioural pattern in obesity also by affecting the different regional fat distribution. PMID- 2099994 TI - [Can the Body Mass Index and the waist:hips ratio (WHR) affect the correlation between impedance measurement and anthropometry in the evaluation of body composition?]. AB - Among the numerous techniques used to measure body composition, this study utilised anthropometric methods (weight, height, circumference and skin folds) and impedance measurement (measurement of bioelectric impedance). Results from the two methods were compared in order to assess whether BMI parameters and the waist/hips ratio (WHR) influenced this correlation. One hundred and eighty patients (133 F, 47 M) were included in the study. Patients were divided into groups according to the degree of obesity expressed as BMI and WHR. Body composition was evaluated using anthropometric methods (according to Garrow Webster, Durnin-Womersley, modified Durnin-Womersley and Jackson-Pollock) and impedance measurement in which resistive bioelectric impedance is measured using a tetrapolar technique. A good correlation was generally observed in the female population between impedance assessment and anthropometric methods, and this correlation was not influenced by either BMI or WHR. In the male group, on the other hand, the correlation between the two methods was limited by BMI greater than 30 and WHR greater than 1. In conclusion, impedance measurement and plicometric methods are generally compatible, but areas of uncertainty arise in the male population with BMI greater than 30 and WHR greater than 1. PMID- 2099995 TI - [Caloric intake and distribution of the main nutrients in a population of obese children]. AB - Calorie intake and the main nutrient contents were assessed in a population of 152 obese (OB) children (86 M; 66 F; age 7-11) and 153 normal weight (NW) peers (87 M; 66 F). The following method was used: a) an interview using a food dictionary to assess food intake during the 2 days prior to the study and on one holiday: and b) a weekly questionnaire. The mean food intake of OB did not exceed that of NW, but on the contrary was lower (OB: 1812.9 +/- 39.6 kcal/die; NW: 1928.5 +/- 39.4 kcal/die; p less than 0.05). The population studied consumed approximately 50% of calories as carbohydrates (CHO), 35% as fats (F) and 15% as protein (P), and no difference was noted between OB and NW. The percentage of CHO was lower than that recommended by LARN, whereas the percentages of F and P were higher. A significant increase with age was noted in F and P intake as was a significant reduction of CO. 70% of OB and 80% of NW matched or exceeded the calorie intake recommended by LARN. 30% of OB and 24% of NW consumed 30% less than the daily calorie intake recommended by LARN. PMID- 2099996 TI - [Energy metabolism at rest and the respiratory quotient in obese and normal weight prepubertal children]. AB - The resting metabolic rate (RMR) was measured in obese (n. 14) and normo-weight (n. 14) pre-pubertal children using indirect calorimetry: correlations between RMR and anthropometric and metabolic parameters were also assessed in order to identify the existence of a causal relationship between the reduction of the RMR and the onset of obesity in children. RMR was expressed as an absolute value and appeared to be higher in obese subjects in comparison to controls (5138 +/- 498 kJ/d vs 4443 +/- 481, p less than 0.0001). If corrected for Kg of fat free mass (FFM), the anthropometric variable which accounts for the major (75%) variations of RMR, resting metabolism in obese subjects was lower than that in normal weight controls (173.2 +/- 20.1 kJ/kg FFM/d vs 189.9 +/- 17.6, p less than 0.05). The lower percentage of metabolic active organs which make up the lean body mass in FFM (brain, heart, liver and kidneys) and the absence of a defect in resting thermogenesis in the obese child could nevertheless explain the reduction of RMR/kg FFM observed in the study. PMID- 2099997 TI - [Postprandial thermogenesis and obesity: effects of glucose and fructose]. AB - In order to check whether reduced postprandial thermogenesis, as found in obese subjects depends on insulin resistance, the study tested whether the thermogenetic response to glucose in a group of obese subjects and a group of normal weight subjects differed from that obtained using an insulin-independent monosaccharide such as fructose. Nine obese subjects and 6 control subjects were included in the study. An oral glucose tolerance and fructose tolerance test (75 g) was performed in all subjects on different days. Energy expenditure was calculated both in basal conditions and during the test (resting metabolic rate: RMR) using indirect calorimetry expressed per kg of lean weight, as assessed using bioimpedance measurement techniques. Blood samples were collected to assay glycemia and insulinemia. Results show that increased RMR induced by glucose was significantly reduced in the group of obese subjects compared to controls. In the same group of obese subjects, RMR was found to be significantly higher following fructose in comparison to the glucose response but did not differ from that in controls. Data confirm the existence of reduced thermogenesis in obese subjects induced by glucose. The fact that this phenomenon was not recorded in the same subjects following the fructose tolerance test, whose metabolism is insulin independent, supports the hypothesis that reduced glucose-induced thermogenesis in obese subjects may depend on insulin resistance. PMID- 2099999 TI - [The relationship between the amount of blood that mosquitoes engorge and their infectivity with the causative agent of malaria]. AB - The infection of mosquitoes with malaria plasmodia was found to be affected by relative (to full portion) blood amount of the infected donor, which they suck out, i.e. to what extent the engorged portion approximates to the limiting one when mosquitoes cease bloodsucking. The facts obtained show that the survival of plasmodia in a mosquito (most likely, the passing of ookinetes into the outer side of the mid-gut) is associated with the degree of its stretching during bloodsucking. The limit stretching may be also attained during feeding up on a healthy donor. PMID- 2099998 TI - [Use of an automatic blood glucose measurement system for the assessment of insulin resistance during the oral glucose tolerance test]. AB - An automatic glycemic control system (Beta-like, Esaote) was used to calculate the insulin area (IA) required to keep glycemia within the normal range during OGTT (using NDDG criteria). IA was calculated by adding total endogenous insulin to insulin infused by the Betalike system (Actrapid HM, Novo). During the test, glycemia was obliged to follow a mean normal curve using an insulin infusion according to a special algorithm which automatically adapted to individual parameter variations during the different stages of OGTT. Fourteen blood samples were collected to assay metabolites (glucose, NEFA, lactate and alanine) and hormones (insulin, C peptide, glucagon). Data on insulinemia and glycemia were used to calculate the respective areas under the total and incremental curve (IA expressed in UL-1 min-1 and GA expressed in mM.L-1.min-1); an insulin resistance index was then calculated (total and incremental) using the following formula: IA/(normal GA/patient GA). This test allows us: a) to evaluate the insulin secretory response to a standard glycemic stimulus represented by a glycemic curve within the normal range; b) to calculate the quantity of insulin necessary to maintain the glycemic curve within the normal range; c) to evaluate the body's total insulin resistance according to an index calculated on the basis of the insulin area required; d) to compare the calculated insulin resistance index with NEFA and glucagon data obtained during the test; e) to identify the exact evolution of these events over time during OGTT. PMID- 2100000 TI - [The initial experience in using discriminant analysis for differentiating close species of ticks in the genus Dermacentor (Ixodidae) by the larval phase based on morphometric data]. PMID- 2100001 TI - [The dynamics of carbohydrase desorption from the surface of the intestines in fish and in their parasitizing cestodes]. AB - Data are obtained on the fixation strength of carbohydrases on the structures of digestive-absorptive surfaces of cestodes and intestines of their fish hosts. A dependence of the parasite's digestive activity on the activity of the host's enzymes has been established. General regularities of desorption dynamics of carbohydrases in studied animals and their specific peculiarities are noted. PMID- 2100002 TI - [Multiple forms of NAD-dependent malate dehydrogenase in 3 species of trematodes of the genus Notocotylus (Trematoda: Notocotylidae)]. AB - NAD dependent malate dehydrogenases of three trematode species, Notocotylus attenuatus, N. ephemera and N. imbricatus, have been investigated by electrophoresis. Seven different zones with 15 isoenzymes in N. attenuatus, 16 isoenzymes in N. ephemera and 11 isoenzymes in N. imbricatus have been found in MDH spectra. Isoenzymes of MDH are controlled by seven polymorphic loci. The activity of isoenzymes of three slowly migrating zones is 10 and more times higher than that of fast zones (4-7). The genotypes of adults in one strain are genetically identical, independent ot the development in different definitive hosts. The spectra of MDH of the investigated Notocotylus species are different in slowly migrating isoenzymes (1-3 zones). PMID- 2100004 TI - Solvent induced conformational changes in renin inhibitor polypeptide. AB - Conformation of the renin inhibitor peptide, Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr Lys (RIP) has been studied in aqueous solution and in lipid bilayers using 500 MHz 1H NMR spectroscopy. Analysis of the NMR parameters indicates that in aqueous solution, RIP exists as a random coil. On incorporation into lipid bilayers, the peptide adopts a rigid and well defined conformation. The N-terminal end is stabilized by the hydrophobic environment of the lipid bilayer. The C-terminal end is located near the lipid-water interface and attains rigidity due to interaction with the phosphate groups of lipids. The observations emphasize the role of environment in stabilizing significantly different conformations of RIP in three different media--D2O, DMSO and lipid bilayers. PMID- 2100003 TI - [The effect of different concentrations of surface-active substances on the size of the circadian rations and on the duration of food passage in Lymnaea stagnalis infected with Echinostoma revolutum parthenitae]. AB - In solutions of the detergent "Kristall" (0.9 and 90 mg.l.-1) there were established statistically reliable differences in the values of day rations and duration of food passing both in infected and free from infection molluscs. In noninfected individuals day rations increase 1.5 to 5 times and the duration of food passing 5 to 7 times. In infected animals the value of day rations decrease and the duration of food passing increases less intensively. PMID- 2100005 TI - Microcalorimetric studies of the interaction of normal and thyrotoxic cardiac myosins with ATP and ADP. AB - The heat production of the interaction of normal and thyrotoxic cardiac myosins with ATP and ADP was studied in a microcalorimeter. As compared to the normal protein the thyrotoxic cardiac myosin gave a larger negative enthalpy, entropy, and heat capacity change. These results indicate that the enthalpy, entropy, and heat capacity differences between the two conformational states of myosin are larger in the thyrotoxic cardiac muscle than in the normal control. The ATP induced transition between the conformational states of the cardiac myosins appears to be connected to the powerstroke of the contractile cycle. Therefore the observed thermodynamic differences between the normal and thyrotoxic cardiac myosins may be related to the active site chemistries of these isomyosins and portend the functional abnormality of the thyrotoxic cardiac muscle. PMID- 2100006 TI - Synthesis and possible applications of biotin-linked copper clusters. AB - The trifunctional aziridine XAMA-7 (CAS 57116-45-7) has been used to form crosslinks between a deep red-violet copper cluster of the type Cu(I)8Cu(II)6pen12Cl5- (pen=penicillamine) and molecules with biological activity such as d-biotin and proteins. A complex containing biotin, bovine serum albumin and the copper cluster displayed activity toward affinity columns of avidin on Agarose, and the red-violet pigment was immobilized on the gel. This interaction was completely blocked in gels which had been pretreated with d-biotin carboxylic acid. The free and biologically active versions of the cluster have some potential for biomedical applications. For example, the short-lived positron emitter 64Cu (suitable for positron tomography) may be carried in the cluster's structure. The cluster is paramagnetic, but it is a relatively weak effector of water proton spin-lattice relaxation. Other members of this structural group of inorganic compounds may have better magnetic properties, and the crosslinking reaction with aziridines appears to be generally applicable to the group. PMID- 2100007 TI - Studies on C17 brown mice subjected to photochemotherapeutic doses of long wave length ultraviolet (UVA) radiation. AB - In this study the risk of photochemotherapeutic dose levels of long wave ultraviolet radiation (UVA) was assessed by employing a laboratory animal system, C17 brown mice. The experimental group was subjected to three UVA dose levels, 1000, 2000 and 3500 J/cm2. The dose regimen 50 J/cm2 per day for five days a week was completed in 4, 8 and 14 weeks respectively. The UVA exposed animals were examined until 52 weeks post UVA exposure periods for morphological lesions. Estimations of DNA, protein levels and dermal, epidermal thickness were made. There were no lesions observed with the highest UVA dose employed. Alterations in the DNA and protein levels in the skin of animals in the exposed groups were observed in the post UVA periods. A notable increase in the DNA level was observed 47 weeks post UVA period. The significance of alterations in DNA and protein levels needs to be studied further for evaluation of long term risk following UVA exposure. The data presented however led to a conclusion that the photochemotherapeutic doses of UVA do not pose any risk of cancer to pigmented mouse strains. PMID- 2100008 TI - Bovine brain low Mr acid phosphatase: purification and properties. AB - Low molecular weight acid phosphatase from bovine brain was purified to homogeneity using affinity chromatography on p-aminobenzylphosphonic acid-agarose to obtain the enzyme with both high specific activity (110 mumol min-1 mg-1 measured at pH 5.5 and 37 degrees C with p-nitrophenyl phosphate as substrate) and good yields. The enzyme was characterized with respect to molecular weight, amino acid composition, pH optimum, Km and Vmax in varying substrates, and to the Ki of varying inhibitors. Furthermore, transphosphorylation to glycerol was demonstrated by measuring the released p-nitrophenol/Pi concentration ratio during the initial phase of the catalyzed reaction. The enzyme was inactivated by iodoacetate and 1,2-cycloexanedione. Inorganic phosphate, a competitive inhibitor, protected the enzyme from being inactivated by the above compounds, demonstrating the involvement of both cysteine(s) and arginine(s) at the active site of the enzyme. Furthermore, the strong inhibition exerted by pyridoxal 5' phosphate and the low inhibitory capacity possessed by the pyridoxal 5'-phosphate analogues pyridoxamine 5'-phosphate and pyridoxal, indicate that at least one lysine residue is present at the active site. PMID- 2100009 TI - Time dependent inhibition of xanthine oxidase in irradiated solutions of folic acid, aminopterin and methotrexate. AB - The xanthine oxidase catalyzed oxidation of hypoxanthine was followed by monitoring the formation of uric acid at 290 nm. Inhibition of xanthine oxidase occurs in aqueous solutions of folic acid methotrexate and aminopterin. These compounds are known to dissociate upon exposure to ultraviolet light resulting in the formation of their respective 6-formylpteridine derivatives. The relative rates of dissociation were monitored spectrophotometrically by determining the absorbance of their 2,4-dinitrophenylhydrazine derivatives at 500 nm. When aqueous solutions of folic acid, aminopterin and methotrexate were exposed to uv light, a direct correlation was observed between the concentrations of the 6 formylpteridine derivatives existing in solution and the ability of these solutions to inhibit xanthine oxidase. The relative potency of the respective photolysis products were estimated. PMID- 2100010 TI - Managing noncompliance in the 'difficult' medical patient: the contributions of insight. A case report. AB - Psychodynamics can interfere with medical compliance, especially in psychologically vulnerable patients. A case is presented of a cancer patient who developed a powerful transference reaction to her oncologist, jeopardizing her treatment for cancer. Strategies for integrating techniques of insight-oriented psychotherapy with those of supportive psychotherapy are discussed in managing such reactions and improving compliance. PMID- 2100011 TI - Brief integrative dynamic psychotherapy for insomnia. Systematic evaluation of two cases. AB - An integrative form of brief dynamic psychotherapy was applied in 2 cases of insomnia. One patient had a sleep-onset latency problem, while the other suffered from early morning awakening. The treatments are described, and data on the long- and short-term effects of therapy are presented. PMID- 2100012 TI - A 5-year follow-up study of psychotherapy. The stability of changes in self concept. AB - This 5-year study examined students who were in individual psychotherapy. The specific interest of the study was in the stability of changes in their self concept after psychotherapy. Students who were patients at the Dental Health Care Unit were used as a control group. Self-concept was measured by a multidimensional measure which consisted of four dependent variables: symptoms, Beck's Depression Inventory, self-image test and general progress during therapy. Changes in self-concept were presented as change profiles which showed that statistically significant changes had occurred in the experimental group during the 5-year follow-up study. However, the profile of the control group remained unchanged. The results of this follow-up study provide strong evidence for the stability of changes produced by psychotherapy. On the basis of LISREL models the 5-year results were best predicted by the 2-year results. The situation at the outset of psychotherapy predicted only 17% of the results after 5 years. PMID- 2100013 TI - Socialization and psychosomatic disease: an empirical study of the educational style of parents with psychosomatic children. AB - Starting from the assumption that psychosomatic diseases are distinct from neuroses and different kinds of socialization tend to predispose to the two disorders, the educational style of parents with psychosomatic children (n = 79, 30 bronchial asthma, 19 ulcerative colitis, 30 atopic dermatitis) and with neurotic children (n = 51) was studied. Children and parents were given questionnaires on parental educational attitudes, techniques and goals. Significant differences were found on various dimensions, which indicate for example closer mother-child ties as well as father-child ties in the psychosomatic families. The results from this study are consistent with the concept of a restrictive socialization in psychosomatic families. PMID- 2100014 TI - Psychosomatic aspects of patients on hemodialysis. 3. Clinical usefulness of alexithymia. AB - The clinical usefulness of alexithymia in dialysis patients was examined from psychosomatic aspects. Before hemodialysis (HD), primary alexithymia was present in 50-53% of HD patients with diabetes. After 2 years' HD therapy, an additional 32-36% of HD patients without diabetes developed secondary alexithymia. In contrast, the prevalence of alexithymia was low in patients receiving continuous ambulatory peritoneal dialysis (CAPD), which requires a higher self-control ability than HD. Alexithymia may reflect dialysis patients' ability to take care of themselves and therefore serve as a useful index in (1) selecting the type of dialysis, either HD or CAPD, and (2) identifying patients on dialysis likely to develop somatic complications due to lack of adequate self-control. PMID- 2100015 TI - Psychosomatic aspects of patients on hemodialysis. 4. The relationship between quality of life and alexithymia. AB - The relationship between quality of life (QOL) and alexithymia was examined in dialysis patients. Hemodialysis (HD) patients with diabetic nephropathy had poor QOL in medical dimension. Although they had good QOL in psychological and social dimensions, a high prevalence of alexithymia associated with self-control ability was observed. These results suggest that their inability to care for themselves was reflected in poor medical dimension, and that good psychological and social dimensions were merely an outward appearance. Therefore, identification of alexithymia in dialysis patients is important along with a three-dimensional evaluation of QOL. Multidisciplinary comprehensive assessment of QOL including alexithymia will lead to a real improvement of dialysis patients' QOL. PMID- 2100016 TI - Non-HIV immunosuppressive factors in AIDS: a multifactorial, synergistic theory of AIDS aetiology. PMID- 2100018 TI - Cellular and molecular aspects of insect immunity. PMID- 2100017 TI - A novel approach to the induction of specific cytolytic T cells in vivo. AB - The induction of specific cytotoxic T lymphocytes (CTL) is one component in the immune response which can effectively protect the host against the progression of many viral infections. CTL are also known to play an important role in immune defence against tumour growth. CTL induction is dependent the presence of the specific antigen, appropriately presented, and interleukin-2 (IL2), provided by T helper lymphocytes. We studied the specific CTL response induced by tumour cells transfected with murine IL2. Our results show that tumour cells manipulated to secrete IL2 induce an improved specific anti-tumour response which results in tumour rejection in mice. To further investigate the effect of IL2 on the CTL response to different antigens, we introduced synthetic peptides into IL2 secreting tumour cells and determined the specific CTL induction in syngeneic mice immunized with these cells. We report here that such IL2-secreting cells can effectively prime peptide-specific CTL in vivo. Our data are relevant to immunotherapy and vaccine development and open up the possibility that autologous cells, manipulated to secrete IL2 and located with one or a cocktail of peptides, could be used to stimulate a specific CTL response. PMID- 2100019 TI - Functional studies on insect haemocytes, including non-self recognition. PMID- 2100020 TI - Transplantation immunity in insects: does allograft responsiveness exist? PMID- 2100021 TI - Acquired immunity in insects: the recognition of nonself and the subsequent onset of immune protein genes. PMID- 2100022 TI - Inducible humoral immunity in insects: does an antibody-like response exist in invertebrates? PMID- 2100023 TI - Depression of immune reactions in insects. PMID- 2100024 TI - Dual functions of insect immunity proteins in defence and development. PMID- 2100025 TI - Possible applications of insect antibacterial peptides. PMID- 2100026 TI - Expression and secretion of insect immune peptides in yeast. PMID- 2100027 TI - [Pneumocystis carinii pneumonia in HIV infections. Committee of the 1st Consensus Conference of anti-infectious therapy organized in May 1990 in Paris by the Societe de Pathologie Infectieuse de Langue Francaise]. AB - At the end of the first consensus conference on anti-infectious therapy organized by the French Language Society of Infectious Pathology in May 1990 and devoted to pneumocystosis in patients with human immunodeficiency virus (HIV) infection, the consensus committee produced this paper which answers the following 4 questions: what are the indications, technical requirements, sensitivity and benefits of induced expectoration in the diagnosis of Pneumocystis carinii pneumonia? what are the initial and secondary severity factors; in which cases is transfer to an intensive care unit indicated; in which manner can treatment be modified? what is the position occupied by corticosteroid therapy in the management of pneumocystosis? when is prophylaxis of pneumocystosis indicated; what prophylactic methods are used and how to choose among them? PMID- 2100029 TI - [Diffuse nodular pulmonary opacities in a HIV positive patient]. PMID- 2100028 TI - [Primary pulmonary lymphoma. Current data. Apropos of 9 cases]. AB - The authors report 9 cases of primary pulmonary lymphoma (PPL). With this report, together with the publication of recent and important studies and with the latest advances in immunology, the principal features of this rare entity are emerging from among other lymphoproliferative pathologies of the lung. As a rule, PPL is a histologically well-differentiated tumour with low malignancy and slow course. Treatment is surgical in localized forms. In extensive forms there is no firmly established treatment, but the absence of clinical symptoms permits therapeutic abstention. PMID- 2100030 TI - [Endothoracic vascular involvement in Behcet's disease]. AB - The observation of 3 cases has prompted the authors to review the characteristics of vascular abnormalities that may be found in Behcet's disease. These lesions, the frequency of which has diversely been estimated, involve the veins more often than the arteries. Arterial lesions occur, after a varying length of time, as occlusions or aneurysms, both treated by surgery. Phlebitis and venous thrombosis may be complicated by severe pulmonary embolism and therefore require anticoagulant therapy. PMID- 2100032 TI - [Fistula of the pulmonary artery after lobectomy extended to the main bronchus]. PMID- 2100031 TI - [Muscular metastasis of primary bronchial carcinoma]. AB - We report 2 cases of muscle metastases from primary lung cancer (an adenocarcinoma and one epidermoid carcinoma). In one patient the metastases revealed the disease. This site of metastasis seems to be exceptional since only 46 cases have been published, but its frequency is probably underestimated. A retrospective study of the last 10 years and an exhaustive review of the literature have enabled us to determine the frequency of muscle metastases from lung cancer and their physiopathological implications. PMID- 2100033 TI - [Amyotrophic lateral sclerosis with multiple myeloma]. AB - Motor neuron diseases (MND) associations with paraproteinemia, lymphoma, hexosaminidase A deficiency and heavy-metal intoxication are of great interest. A case of amyotrophic lateral sclerosis (SLA) associated with multiple myeloma (monoclonal IgG paraproteinemia and K light chains) is reported. The detection of abnormal protein in 1988 and the increase of its serum level during 1989 were strictly correlated with the beginning and the worsening of the neurological disease. Shy and coll. in 1986 affirmed that association of paraproteins with MND is probably not merely the fortuitous association of a common laboratory abnormality and an uncommon disease. The reported case provides elements for a causal association between paraproteinemia and MND. PMID- 2100034 TI - [Occasional disclosure of large arachnoid cysts in 2 subjects]. AB - Two old men in whom the CT and MR scans had unexpectedly shown an enormous arachnoid cyst in the fronto-temporo-parietal region, underwent neuropsychological examination. This did not show any neuropsychological abnormality. This is in accordance with the hypothesis that the cyst represents a dysontogenetic disorder with very slow growth, leaving functionally normal the cerebral structures shifted. PMID- 2100035 TI - [Clinical study of two families with late-onset autosomal dominant spinal cerebellar ataxia linked with HLA. Preliminary results]. AB - Two families with autosomal dominant spinocerebellar ataxia (SCA) of late onset were studied. These families originate in the same small rural area in a Southern Italian region (Calabria). We report the clinical study of 23 patients in different stages of the disease and neuropathological study in one patient. Linkage studies provided strong evidence for linkage of the SCA locus to the HLA loci (SCA1) in the subjects of these families. Our study allows to outline the clinical features of HLA linked SCA in order to trace a pattern of SCA1 phenotype thus making easier the identification of SCA1 heterozygotes in an early clinical stage. PMID- 2100037 TI - [Phenotypic and functional characterization of cloned T-lymphocytes from cerebrospinal fluid of patients with multiple sclerosis]. AB - T cell clones derived from the cerebrospinal fluid of patients with multiple sclerosis were investigated for their ability to produce IL2, IL4, IFN gamma and TNF alpha. As controls, liver infiltrating T lymphocyte clones from patients with chronic active hepatitis were used. All CSF clones (both CD4+ and CD8+) produced high amounts of IFN gamma and particularly of TNF alpha. TNF was synthesized in a significantly higher amount than control clones. Moreover, they were capable of secreting IL2 but not IL4. From our results we conclude that CSF-CD4+ T clones could constitute a subset with functional properties similar to those of the Th1/inflammatory cells of the mouse. The unusually high amount of TNF produced by CSF derived T cell clones strongly suggests a significant role for this cytokine in MS immunopathogenesis. PMID- 2100036 TI - [Nuclear magnetic resonance: a comfortable diagnosis]. PMID- 2100038 TI - [Palm stimulation in carpal tunnel syndrome]. AB - In order to verify the sensory nerve conduction velocity (SNCV) by median nerve palmar stimulation regard to each single finger, we tested 48 patients with typical CTS symptoms, confirmed by neurophysiological examination. The control group consisted of twenty-seven healthy volunteers, of similar mean age. The SNCVs were obtained by stimulating the II finger (M2), III (M3), IV (M4) and II and III intermetacarpo-phalangeal site (respectively P2 and P3) for median nerve; IV finger (U4) and IV intermetacarpophalangeal site (P4) for ulnar nerve. Data show that P2 was normal in 3 cases (6.2%), as was M2; M3 in 2 cases (4.2%) and P3 only in one case (2.1%). No sensory nerve action potential was recorded in 3 case (6.2%) during P3 stimulation, in comparison to 14 cases (29.2%) during M4 stimulation. When each case was examined separately, the behaviour of palmar SNCV resulted similar to the corresponding fingers. Finally, the ratio between SNCV values of P2/P3, with respect to controls, showed a further more severe damage of P3 compared to the P2, generally preferred by other authors. PMID- 2100039 TI - [Venous angioma associated with cavernous angioma. Presentation of three cases]. AB - Cavernous angiomas and venous angiomas may be discovered as associated lesions in the same patient. Most Authors report that Venous angiomas are not true vascular malformation; they should be considered as variant of normal venous drainage, consisting of tortuous medullary veins converging into a dilated draining one. By rule, they are quite asymptomatic, and very rarely bleed. On the other side, cavernous angiomas are true vascular malformations, usually angiographically occult. Their association is relatively rare, but it is important because of the possibility of bleeding, which should be related to the presence of the cavernous malformation. We report the cases of three patients studied by Computed Tomography, Magnetic Resonance and Digital Angiography in our Neuroradiologic Department. PMID- 2100040 TI - [The verbal fluency test for the diagnosis of dementia]. AB - Two forms of verbal fluency test, phonological (FF) and semantic (FS) sets, have been administered to four groups of demented patients: 11 with Alzheimer-type dementia (DAT), 13 with multi-infarct dementia (MID), 8 with Parkinson-Dementia (P-D) and 11 with adult chronic hydrocephalus (ICA). Patients were matched for age, educational level and neuropsychological impairment pattern. Further, ten neurologically healty subjects were selected as control group. Control subjects result to be different from all other groups in both FF and FS; moreover, FF test results to be more impaired in ICA than in DAT. Furthermore, FF is more impaired than FS in P-D and ICA patients. On the basis of our results, verbal fluency tests might represent an useful instrument to differentiate demented subjects from non-demented ones and within demented groups to characterize the different neuropsychological pattern of the cortical and subcortical type of cognitive deterioration. PMID- 2100041 TI - [Mitochondrial oculopharyngeal myopathy: description of a case]. AB - We describe a 55 years old man affected by eyelid ptosis, mild ophthalmoplegia externa and severe dysphagia owing to pharyngoesophageal dyskinesia. Skeletal and eyelid constrictor muscles EMG showed myogenic alterations. Muscle histological findings of ragged red fibers and oxidative histochemical alterations, together with ultrastructural investigation clue for mitochondrial myopathy diagnosis. This, considering the unusual clinical aspects of the case, confirms as mitochondrial disease can widely vary in their phenotypical expression. PMID- 2100042 TI - [Diagnostic and prognostic value of the echo-Doppler and transcranial Doppler methods in the acute phase of ischemic ictus]. AB - The ischaemic ictuses are a frequent pathology. For their annulling potentiality a quick etiopathogenetic diagnosis is necessary to institute a suitable therapy that limiting the extension of the cerebral damage. In this respect, it is fundamental the use of the duplex methods in real time together with doppler valuation of the neck vessels (carotid and vertebral) and of the intracranial big arteries. The direct observation of the endoluminal surface in the extracranial vessels and the valuation of the circulatory condition in the individual arterial districts explored give as important of haemodynamic information which, added to that obtained through a computerized axial tomography and the clinic, allows a correct diagnostic valuation with important effects on the therapy as well as a reliable prognostic formulation. Description of two clinical cases. PMID- 2100043 TI - [Alterations of smooth-pursuit ocular movements in Alzheimer's disease]. AB - Recent findings suggest that patients affected by Alzheimer's disease (AD) have evident alterations of smooth-pursuit ocular movements induced by a sinusoidal predictable target. For a better understanding of the possible modifications of this performance in patients with AD we evaluated, using a quantitative method, the smooth-Pursuit induced by ramps with constant, unpredictable velocities. Twelve patients with probable AD were studied. These patients were compared with twelve age matched healthy volunteers. Visual inspection of our recordings shows that AD patients have frequent, large saccades intrusions which in some cases appeared to disrupt smooth tracking, particularly for low target speeds. Furthermore, the smooth-pursuit eye velocity induced by target of high speed is significantly reduced in respect to that present in our control group. Some significant correlations between altered smooth-pursuit parameters and abnormal psychometric scores were noted. PMID- 2100044 TI - [Memory changes in herpes virus encephalitis: report of a case]. AB - A case of Herpes Simplex Encephalitis with a benign course was present in a 66 year-old patient. A year after the acute phase of the illness, the patient continued to suffer from inability to fix verbal material in memory. During the acute phase, cerebral NMR revealed a large evolving lesion in the right temporal region, and an old lesion located in the same region of the opposite hemisphere. From the medical history, we learned that the patient, 35 years earlier, suffered a similar episode, including a short-term memory deficit. In the following study, we will discuss this case report in relation to data found in the literature dealing with memory deficit, caused by mono and bilateral, temporal lesions. PMID- 2100045 TI - [Neurolinguistic analysis of a case of pure agraphia]. AB - A patient with a pure acquired dysgraphia is reported. The pattern of the patient's performance is discussed in relation to current functional models of writing. The case may be interpreted by assuming a selective impairment to the graphemic buffer. PMID- 2100046 TI - [The apomorphine test for diagnosis of parkinsonian syndrome]. AB - Apomorphine is a powerful dopaminergic drug, able to improve cardinal symptoms of Parkinson's disease in few minutes, when injected subcutaneously. We administered different doses of apomorphine s.c. against placebo in 25 patients with a Parkinsonian syndrome, with the aim of discriminating Parkinson's disease from other Parkinsonism. A positive response to apomorphine was predictive (88%) of good responsiveness to levodopa therapy. Our data, together with those of other groups, indicate that apomorphine test is a useful tool in the diagnosis of Parkinsonian syndromes. PMID- 2100047 TI - [A case of cerebral angioma: non-invasive instrumental diagnosis]. AB - A case of cerebral angioma: non-invasive assessments. A 65-year-old woman, suffering from epileptic seizures since the age of 6, was examined. Transcranial Doppler (TCD) ultrasounds, SEPs and EEG brain mapping by means of median nerve stimulation, were performed, followed by a NMR of the brain, which revealed an arteriovenous malformation in the left hemisphere (frontal and parietal lobe). By comparing the results of the neurophysiological tests, the diagnostic value of TCD, confirmed by the neuroradiologic findings, was established. EEG and SEPs were also abnormal, but their actual effectiveness in clinical studies is discussed. We conclude that these electrophysiological examinations do not allow a reliable diagnosis as with TCD. PMID- 2100048 TI - [P300 and Parkinson disease. The role of cognitive changes]. AB - Cognitive disturbances are frequently encountered in advancing Parkinson's disease (PD). Typically there are visuo-spatial disorders, memory impairment and bradyphrenia, defined as 'subcortical dementia' to distinguish it from the dementia that occurs in Alzheimer's disease, where the most prominent dysfunctions are agnosia, apraxia and aphasia. An electrophysiological test to study cognitive processing is the P300 (or P3) of the Event Related Potentials; in particular the latency of the P3 seems to correlate with cognitive decline. Thirty patients affected with idiopathic PD were investigated using a classic auditory "oddball" paradigm (rare tone--"target"--3000 Hz, frequent tone--"non target"--1000 Hz; the patients were instructed to recognize and keep a mental count of the number of rare tones). Electrophysiological findings were compared with those obtained in twenty normal subjects, age and sex matched with the patient's group. The parameters of P300 were correlated with patient's age, duration of the disease, motor and cognitive impairment levels and L-Dopa therapy. The P300 was loss in 16.6% (5 p.) and delayed in 33.3% (10 p.). Significative correlations were found only with age and cognitive impairment scores, but not with other variables analyzed. These results suggest that P300 could be a useful test to identify demented patients among those with PD, despite different motor disabilities. PMID- 2100049 TI - [The study of sleep in full term and preterm neonates with EEG polygraphy]. AB - We accomplished polygraphies in two groups of infants: 1) preterm infants born before 33 weeks CA, and recorded between 33 and 48 weeks CA; 2) full term infants, recorded between 39 and 48 weeks CA. We compared in each group of infants: 1) the development of behavioral states organization; 2) the maturation of cortical bioelectric activities; 3) the development of concordance between behavioral states and EEG pattern; 4) sequences of behavioral states and EEG pattern when the babies fall asleep. In all the aspects considered, we describe some developmental changes, to understand how, through these changes, the newborn sleep-wake ultradian cycle is replaced by 24 hr-cycle, typical of the infantile period. This basic process is expression of maturation of the central nervous system because it is related to CA and not to extrauterine experience. The EEG polygraph usually used in clinical practice allow us to follow these extraordinary transformations very closely. PMID- 2100050 TI - [Parkinson disease and cognitive evoked potentials]. AB - The Authors introduce some questions concerning cognitive impairment in Parkinsonian patients and they focus the attention on 'bradyphrenia'. They briefly discuss the methodological difficulties in studying this kind of disturbances in Parkinson's disease (PD) and the approach to this problem with the help of the Event-Related Potentials or ERPs. Finally, they review literature and their data on Contingent Negative Variation (CNV) and P300 in PD and conclude that interesting and useful informations can be obtained by means of the electrophysiological methods. PMID- 2100051 TI - [Correlations of heart rate and arterial pressure in the orthoclinostatic test. Study of 3500 subjects]. AB - The study deals with the data resulting from the analysis of 3497 passive orthoclinostatic tests performed in the neurological Clinic of Pisa during the last 10 years. Blood pressure and heart rate values both in supine and upright positions have been analyzed, particularly focusing the orthostatic hypotension, which were 184 over 3497 tests. The results show that in young subjects only hypersympatheticotonic hypotension are present, due to a dysfunction of the regulating hypothalamic centres, while at more advanced age there is a prevalence of orthostatic hypotension with low differential values of heart rate. Differential values of heart rate as a function of age have been the calculated. PMID- 2100052 TI - [Changes in muscular excitability and contractility caused by fatigue in Steinert's disease]. AB - To study effects of fatigue on muscle excitability and contractility in myotonic dystrophy (MyD), we evaluated, by ulnar nerve supramaximal stimulation, both single shock and 40 Hz tetanus, M wave and force parameters from adductor pollicis. In 8 MyD patients and in 6 controls amplitude of M wave, electromechanical delay, single twitch and tetanus tension, contraction and half relaxation times were recorded in basal condition and at different times after 75 sec. of maximal voluntary contraction. Reduction of force related to fatigue was per cent lesser in MyD compared to controls. Electro-mechanical delay, basally longer in MyD, showed after fatigue 15% increment compared to 47% in controls. Half-relaxation time increased in both groups, but in MyD recovery was faster. Peculiar alterations of excitation-contraction coupling and contractility occurring in MyD can explain the observed modifications of fatigue phenomena in this disease. PMID- 2100053 TI - [A case of central pontine myelinolysis: clinical and electrophysiologic findings]. AB - We described a case of Central Pontine Myelinolysis, typical with regard to pathogenesis (excessive correction of hyponatremia), neuroanatomical damage revealed by imaging techniques (Magnetic Resonance Imaging) and clinical symptomatology. Serially performed BAEPs recordings during patient's hospitalization, showed interesting data on functional recovery which well correlate with the evolution of clinical symptomatology. These data strongly suggest the usefulness of such electrophysiological technique for a prognostic evaluation. PMID- 2100054 TI - [A case of thrombosis of the superior longitudinal sinus]. AB - A case of cerebral venous sinus thrombosis is described in a forty-two years old patient. The literature is reviewed about clinical presentation and neuroradiological findings. We consider the use of NMR in diagnosis. PMID- 2100055 TI - [Arteriovenous malformations: clinical and neuroradiologic study]. AB - We report our experience in clinical and neuroradiological findings on the vascular malformation in our department from January 1988 to March 1990. We have discussed the actual diagnostic modalities and have reviewed the literature. PMID- 2100056 TI - [Echography and venous pathology]. AB - When performed by a well-trained operator, ultrasonic exploration of the deep veins has a more than 90% sensitivity and specificity in the diagnosis of deep vein thrombosis. Despite technical problems in the ileal and sural regions, it is the first examination to be carried out in patients with clinical signs of venous thrombosis. In distal thrombosis of the leg and calf ultrasonography might even be more sensitive than phlebography. In superficial phlebitis ultrasounds can be used to evaluate the extent of thrombosis. In varicose vein disease, they are also a crucial element in the choice of treatment. PMID- 2100057 TI - [Color Doppler echocardiography]. AB - Colour-coded doppler echocardiography uses a pulsed doppler shooting lines scanning system to perform a true real-time doppler angiography of intracradiac flows. Combined with ultrasonic imaging, it has proved irreplaceable for the diagnosis of leakages and for direct visualization of intracradiac shunts; by determining the anatomical location of the jet it facilitates an accurate pulsed and continuous Doppler study. Aortic leakages are best evaluated by measuring the jet at its point of origin. The quantification of moderate to medium leakages remains difficult since it depends on numerous factors and needs integration of other echocardiographic data. Echocardiographic contrast tests after intravenous injection of microbubbles diagnose the right-to-left shunts by the passage of contrast into the left cavities, and the left-to-right shunts by a washing image. PMID- 2100058 TI - [Echocardiography by the transesophageal route. Technique and the main clinical indications]. AB - Transoesophageal Doppler-echocardiography is a new heart imaging technique avoiding many of the problems which sometimes limit standard transthoracic exploration. The transducer, mounted on a fibroscope sheath, is introduced into the oesophagus and therefore lies in the immediate vicinity of the atrial complex, the mitral valve, the aortic valve and the different segments of the thoracic aorta. The examination can be carried out on ambulatory patients in the echocardiography laboratory. The main clinical indications of this technique are: studies of prosthetic valves (notably the mitral valve); detection of vegetations or annular abscesses in infective endocarditis; determination of an emboligenic focus after arterial embolism; study of the causative mechanism in mitral valve regurgitation; pathology of the thoracic aorta and, in particular, of aortic dissection. The usual lack of difficulty in skilled hands, the quality of the images obtained and the diagnostic value of information collected by this route explain why this relatively new technique has very rapidly progressed from evaluation to routine use in most echocardiography laboratories. PMID- 2100059 TI - [Scanner in cardiac and vascular pathology]. AB - Computerized tomography (CT) has become a routine examination, but it is not well suited to the study of vascular and cardiac pathology. However, CT scans are very useful in the diagnosis and monitoring of aortic aneurysms and dissections, in the postoperative follow-up of surgical cardiac patients and in some cardiac pathologies, such as thrombosis or tumors. PMID- 2100060 TI - [Nuclear magnetic resonance imaging in cardiology]. AB - Magnetic resonance imaging (MRI) is particularly well suited to cardiovascular studies since the spontaneous contrast between circulating blood and the cardiac and vascular structures is excellent. The theoretical principles and technical modalities of MRI are summarized prior to describing its cardiovascular applications. Owing to the quality of its anatomical images MRI was first used in daily practice to complete or replace other imaging methods. Its applications are illustrated here. They include aortic pathology (aneurysm, dissection, postoperative control), complex congenital cardiac pathology, hypertrophic cardiomyopathy, heart tumours, post-infarction ventricular aneurysms, and pericardial pathology. The applications of MRI that are currently being evaluated or developed are described. Due to the recent acquisition of cinematographic images MRI is now capable of evaluating the cardiac function. As for the use of MRI to characterize the cardiac muscle, this is a highly original application which may soon become an interesting diagnostic tool. PMID- 2100061 TI - [Isotopes and myocardial ischemia]. AB - Single photon emission computed tomography (SPECT) is superior to conventional radionuclide scintigraphy. The most widely used marker is thallium-201, despite the fact that it is not exclusively flow-dependent. Thallium-201 SPECT can be performed in patients at rest, during exercise followed by a redistribution study, under dipyridamole or nitrate infusion, or combined with spasm provocation test. When performed at rest, it is helpful to diagnose and, above all, quantify a myocardial infarction. Under nitrate infusion, it delineates the viable muscle remaining around the infarct. During exercise or under dipyridamole infusion, it is more effective than any other non-invasive method in detecting myocardial ischaemia (sensitivity 95%, specificity 90%). Following surgical revascularization, a normal exercise SPECT indicates a functional aorto-coronary bypass in 80% of the cases. It is a good method to detect post-angioplasty restenosis (sensitivity 82%, specificity 86%, negative predictive value 93%). Like all paraclinical examinations, SPECT has its limitations: left bundle branch block, reverse redistribution, non-ischaemic (i.e. dilated or hypertrophic) cardiopathies. PMID- 2100062 TI - [The role of isotope methods in evaluating the left ventricular function]. AB - Cardiac angioscintigraphy is a non-invasive, reproducible and reliable technique used to obtain a number of cardiac function parameters, the most important of which is left ventricular ejection fraction. Methodologically, the examination is simple. Fourier's analysis (a mathematical decomposition of ventricular mechanics) provides additional information on some abnormalities and is particularly useful in segmental kinetics studies and in the topographical diagnosis of cardiac rhythm disorders. The technique is indicated mainly for prognostic evaluation and follow-up of patients with left ventricular dysfunction. Metaiodobenzylguanidine (MIBG) cardiac scintigraphy makes it possible to evaluate the reuptake of noradrenaline by neurons, which represents the inactivation pathway of adrenergic neurotransmission and is the principal factor of noradrenaline extraction. MIBG scintigraphy is an indirect way of evaluating left ventricular function in congestive heart failure, as suggested by the results of studies showing correlations between MIBG uptake, left ventricular function indices and disease severity as judged on the basis of evolutive parameters. PMID- 2100063 TI - [Treatment of acute respiratory insufficiency in AIDS]. PMID- 2100065 TI - [Laser in the treatment of common angioma]. PMID- 2100064 TI - [Are calcium channel inhibitors nephro-protectors? Response expected in a few years]. PMID- 2100066 TI - [Aortic stenosis. Etiology, physiopathology, diagnosis, course and prognosis]. PMID- 2100067 TI - [Alveolar syndrome and interstitial syndrome]. PMID- 2100068 TI - [Spinal injuries. Diagnosis, course and prognosis, principles of treatment]. PMID- 2100069 TI - [Mental disorders related to organic diseases. Diagnosis and treatment]. PMID- 2100070 TI - [Intracranial hypertension, entrapments. Physiopathology, diagnosis, treatment]. PMID- 2100071 TI - Parasitic associations with malignant neoplasms. PMID- 2100072 TI - Association between intestinal parasitoses and nutritional status in 3-8-year-old children in northeast Thailand. AB - To assess the prevalence and species of intestinal parasitoses and to evaluate the effects of parasitic infections on the nutritional health of northeastern Thai children a survey was carried out among 343 urban and rural 3-8-year-olds in Sakon Nakhon province. Approximately 57% suffered from single or multiple helminthiasis (ancylostomiasis (AD), ascariasis (AL), opisthorchiasis (OV) and/or strongyloidiasis (SS)) and/or giardiasis (GL). In rural areas the prevalence of AD and SS was higher than in urban areas (p less than 0.01 and p less than 0.05 respectively). OV was found more frequently among 6-8-year olds (18%) than among 3-5-year olds (5%); among 3-5-year olds the prevalence of GL was higher than among 6-8-year olds (17 vs 8%). Multiple infections were observed in 13% of the children. Infected children showed lower daily intakes of protein, iron and riboflavin as well as lower menas for haemoglobin, haematocrit, serum ferritin, and Z-score height for age than non-infected children. The prevalence of stunted children was lower among non-infected children (32%) than among infected children (53%), and children with AL (49%), SS (55%), and GL (45%). Anaemia was found more frequently among the infected children (59%) and GL-children (61%) than among non infected children (42%). Inadequate daily intake of energy and nutrients of most of the children, in combination with parasitic infections, still common in rural northeast Thailand, was shown to result in a serious public health problem. PMID- 2100073 TI - Chloroquine-resistant Plasmodium falciparum malaria at Nchelenge, northeastern Zambia. Follow-up on 515 hospital patients. AB - From 1986 until 1988 chloroquine sensitivity of Plasmodium falciparum malaria was monitored in 515 hospital patients in Nchelenge district, northeastern Zambia. After treatment with chloroquine 30 mg base/kg, bloodslides were examined on day 2, 4, 6 and 7. The overall resistance rate was 21.4%, of which 29% was R1-, 30% R2-, 18% R3- and 23% R2-3 resistance. Resistance rates were negatively correlated with age and positively with the initial parasitemia. It is suggested that in vivo tests of chloroquine sensitivity also reflect the host's immune status for malaria. In rural areas with chloroquine resistance in vivo testing should be performed on all malaria patients. PMID- 2100074 TI - Typhoid perforations of the ileum. A review of 59 cases, seen at Agogo Hospital, Ghana, between 1982 and 1987. AB - In Agogo Hospital in the forest zone of Ghana, 59 consecutive cases of typhoid perforation (TP) of the ileum, occurring between August 1982 and January 1987 were studied retrospectively. Perforation occurred in one patient while on admission in the hospital; all other patients presented with TP. Aneosinophilia was seen in 21/28 = 75%; pneumoperitoneum at radiography or fluoroscopy was present in 16/23 = 70%; neither test proved either satisfactorily sensitive or specific for the diagnosis of TP. In 24 out of 31 patients, ileal perforation occurred in the first week of fever. The mean time for perforation was six days after onset of fever. Late perforation was not associated with higher case fatality rate in this series. Survival was 68%, in accord with most reports on surgically treated TP. Delay in surgery over 2 days after perforation was significantly associated with higher mortality. Outcome was significantly more favourable in children than in adults. PMID- 2100075 TI - Anthropometric assessment of nutritional status of Nigerian children. AB - Anthropometric evaluations of mid-arm circumference, mid-arm muscle circumference, triceps skinfold, upper arm muscle and fat areas were carried out in 348 healthy Nigerian primary school boys and girls aged 7 to 13 years. Measurements were related to centiles derived from the United States Health and Nutrition examination survey of 1971 to 1974. For all measurements, a large proportion of the subjects fell below the 5th centile. Anthropometric reference standards used to indicate nutritional depletion in developed countries may not be appropriate to assess nutritional status of Nigerian children. PMID- 2100076 TI - Sickle cell disease in permanent residents of mountain and low altitudes in Saudi Arabia. AB - Report of a comparative study of sickle cell disease in permanent residents of mountain and low altitudes in south-western Saudi Arabia. The ambient oxygen tensions at these altitudes are 14 and 19 kPa (112 and 144 mmHg) respectively. The frequencies of sicklaemic-related illness requiring medical intervention, and hospitalisation due to crisis and complications of the disease, were about twice as great in highlanders as in lowlanders. The incidence and severity of the complications were similar in both locations. No splenic syndrome was observed in those with the disease or trait in either location. Haemoglobin concentration was 10% greater in mountain normals than in their lowland counterparts; the corresponding figure for sicklers was 5%. Erythrocyte 2,3 diphosphoglycerate concentration was 13% greater in mountain than valley patients; the corresponding figure for normals was 4%. We propose that the elevated diphosphoglycerate in mountain patients might contribute to their higher frequency of sicklaemic illness as well as partially blunting their erythropoietic drive. PMID- 2100077 TI - Senile cataract and glucose-6-phosphate dehydrogenase deficiency in Indians. AB - Erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) was tested in 163 cases of senile cataract and 79 age- and sex-matched controls. There was no statistically significant difference between the overall incidence of G-6-PD deficiency in cataract in comparison to controls. However, amongst the cataract patients the frequency of G-6-PD deficiency was significantly higher in the age group 40 to 50 years (12.1%) as compared to those aged 51 years or more. PMID- 2100078 TI - Surgical rates in Africa. Variations and their possible explanations. AB - Output of six major operations (herniorrhaphy, caesarean section, prostatectomy, hysterectomy, appendectomy and lens operation) have been studied in selected rural parts of Kenya and Tanzania and compared to corresponding national rates in the US, England/Wales and Sweden. African rates of major surgery appear to be at least 20 times lower, on the average, than in Western countries, with large variations between districts and between years. Possible explanations are discussed, such as differences regarding demography, morbidity pattern, socio economic consumer characteristics and locally accessible health care resources. It is concluded that more precise evaluations of the importance of the identification factors cannot be done on the basis of existing health information. More detailed data are required through improved health information systems particularly in developing countries. PMID- 2100079 TI - Psychological disturbance in African Tanzanian epileptics. AB - 138 (60%) of 230 African patients with epilepsy consecutively referred to the neurology clinic, Muhimbili Medical Centre, Dar es Salaam, had a psychological disturbance warranting intervention. 81% of them had only minor disturbance, dominated by neurotic disorders. 19% had a major disturbance dominated by a schizophrenic form of psychosis. Other major disturbances were hysterical reactions, agarophobia and severe depression. Organic brain disease was significantly associated with psychological disturbance. Over 80% of patients with major disturbance had epilepsy and brain-lesion and 77% of patients with minor disturbance had evidence of an organic brain lesion. Organic brain lesion and psychological disturbance was overwhelmingly associated with social disadvantage. Although the social attitude to epilepsy is still negative in Africa, psychological disturbance and social disadvantage in the African Tanzanian epileptic seem to be more strongly related to an organic brain lesion than to be a result of the individual reaction to social prejudices. PMID- 2100080 TI - Famine in southern Ethiopia 1985-1986. Malnutrition, diarrhoea and death. AB - During the 1985-86 famine children from two areas in Southern Ethiopia were studied to assess a possible association between malnutrition and diarrhoeal disease. Malnutrition did not increase the incidence of diarrhoeal disease. However, malnourished children were more severely affected by the infection. Nutritional rehabilitation reduced the demand for treatment of diarrhoea and probably contributed to a decrease in crude childhood mortality. PMID- 2100081 TI - Septicaemia caused by an imported strain of multiply antibiotic resistant Salmonella typhi successfully treated with ciprofloxacin. AB - A case of typhoid fever caused by a multiply antibiotic resistant strain of Salmonella typhi is reported. The S. typhi strain was resistant to ampicillin, chloramphenicol and sulphamethoxazole-trimethoprim. Treatment with cefotaxime, resulted in a clinical and bacteriological cure, but the infection relapsed within a month after completion of therapy. It resolved completely with oral ciprofloxacin with no relapse after a follow up period of one year. To our knowledge this represents the first such reported case in South Africa. The role of ciprofloxacin in treating infections caused by multiantibiotic resistant S. typhi is also discussed. PMID- 2100082 TI - Evaluation of force requirements during use of recycled plastic syringes. AB - Forces required to withdraw the piston in recycled syringes were investigated. New disposable syringes were used as a reference. The force required in withdrawal of the piston for recycled syringes was between 3 and 8 times that required for the reference syringes. Lubrication reduced the force for the recycled syringes substantially. A modification of syringe recycling protocol is suggested. PMID- 2100083 TI - Tuberculous lymphadenitis in Cairo, Egypt. PMID- 2100084 TI - [Obstructive disorders of urine transport in the upper urinary tract--vascular and inflammatory causes]. AB - Vascular and inflammatory causes of ureteral obstruction may be difficult in diagnosis and are recognized often too late. Symptoms, diagnostic approach and therapeutic measures are described in detail. PMID- 2100085 TI - [The significance of citrate excretion and calcium/citrate quotients in urine in patients with calcium calculi]. AB - In 111 patient suffering from calcium oxalate lithiasis more than 168 citrate and calcium analyses have been performed in 24 hour urine. In 69 patients with a single stone episode no significant difference of citrate concentration was found in comparison with 63 healthy volunteers. However, in 42 recurrent stone formers was the citrate concentration significantly diminished (p less than 0.005). The calcium/citrate ratio was in recurrent stone formers markedly higher (5.19 +/- 8.6) than in patients with a single stone episode (3.34 +/- 4.9). However, because great deviation of citrate values the calcium/citrate ratio may not be suitable for evaluation of stone formation risk. PMID- 2100086 TI - [A concentration measuring error-induced calculation error in determining uric acid clearance in dialysis: a simulation study]. AB - Three calculation methods to estimation of the total clearance of dialysis patients are evaluated. The basis of calculation are concentration values of urea in blood versus dialysate. The variation coefficient of the measurement errors is 5 percent. The error formation in three estimation formulas is examined. The formula [formula: see text] is most suitable, if as evaluation criteria the variation coefficient of the estimation error are used. The parameters like dialysate flow, blood flow, ultrafiltration rate and dialysate volume are of relative value. PMID- 2100087 TI - [Determination of secretory immunoglobulin A in urine of children with enzyme immunoassay]. AB - The estimation of secretory immunoglobulin A (sIgA) by an enzyme immunoassay (EIA) was used as heterogenic solid-phase assay. A monoclonal antibody directed against the human secretoric part and a peroxidase-marked anti-IgA serum may mediate the reaction. The test was evaluated on urine of 59 healthy children aged from 0-14 years. An age-dependent increase of sIgA concentration (mg/l) and excretion up to the 6th months of life was found. Thereafter the concentration did reach a constant value of 0.5 mg/l sIgA and 0.4 mg sIgA/g creatinine, respectively. The normal values may follow a logarithmic distribution. The presented method is highly sensitive, simple and safe. PMID- 2100088 TI - [Prognosis of acute dialysis dependent renal failure]. AB - In a retrospective study of 116 patients with acute renal failure treated by hemodialysis the prognostic value of various clinical data was evaluated by discriminant analysis. With a letality of 73.6% the patient survival was dependent on the frequency of associated organ disorders. The following order was prognostical important: respiratory insufficiency, age, cardio-vascular complications and infection or sepsis. Other problems like gastrointestinal complications, coagulation disorders and hepatic failure were without significant value. PMID- 2100089 TI - [Johann Andreas Eisenbarth (1663-1727]. AB - In honour the life of the important occultist and barber Johann Andreas Eisenbarth (1663-1727) is described. His name lives over the centuries in songs and romans and represented the traditional poor type of contemporary surgeons. But in the last decades this picture have been revised by research. In a short review of his life way these new therapeutic measures are presented. His therapeutic work in difference of his colleagues is described. PMID- 2100090 TI - [9th International Symposium of Operative Andrology]. PMID- 2100091 TI - [Hungary/East Germany--Urinary Calculus Symposium Budapest 19/20 April 1990]. PMID- 2100092 TI - [Obstructive disorders of urine transport of the upper urinary tract--benign and malignant retroperitoneal fibrosis]. AB - Our experience in diagnosis, treatment and follow-up course of patients suffering from benign and malignant retroperitoneal fibrosis are reported. Especially in idiopathic fibrosis the initial placement of percutaneous nephrostomy and long term immunosuppression is the treatment of choice. In the follow-up ultrasonography and computerized tomography are valuable methods. PMID- 2100093 TI - [ESWL with the Lithostar--experience with 3,000 treatments]. AB - The experiences with 3,000 extracorporeal shock wave lithotripsies of kidney and ureteral calculi using the Lithostar are reported. Indications, contraindications and therapeutic approach are reviewed and the importance of out-patient follow-up is stressed. The success rate of 75% (including further spontaneous passage of residual desintegrated calculi) is good in the view of an unselected and unfavourable patient population. In the other patients a second ESWL treatment may be necessary. In the initial period in 6% of the patients percutaneous nephrolitholapaxy or open operation have been performed whereas in the last 100 patients it was not necessary. PMID- 2100094 TI - [Endoscopic removal of urinary calculi in children]. AB - In 55 children less than 14 years old urinary calculi have been removed endoscopically. In larger stones the ultrasonic lithotripsy has been used. Due to our experience and a review of the literature it was found that the majority of urinary calculi in children could be removed endoscopically. The open operation should be used in exceptional cases. Problems, results and complications of the endoscopic approach are described in detail. PMID- 2100095 TI - [Laboratory diagnosis of cystinuria]. AB - Delayed diagnosis, apparently due to insufficient knowledge of partly simple methods of cystine determination and their practical application, is often a particular problem in the treatment of cystine lithiasis. The present paper gives a survey of a variety of laboratory methods to determine cystine in the urine both qualitatively and quantitatively. Their applicability in various diagnostic situations is discussed. In clinico-chemical routine, colorimetric cystine determinations using Brands test, but partibularly the nickel/dithionite reagent, is an established and reliable laboratory method. Possibilities of its use as quick screening assays are described. PMID- 2100096 TI - [Comment on the contribution "Loss of bone substance in long-term dialysis--value of serochemical parameters"]. PMID- 2100097 TI - Classification of the follicle population based on oocyte diameter and number of granulosa cells in the ovary of large-eared hedgehog, Hemiechinus auritus gmelin. AB - The present study includes the classification of ovarian follicle population in H. auritus on the basis of oocyte diameter and granulosa cell layers. Our observations revealed that there was direct relationship in the oocyte diameter and the follicle size under a certain limit. Diameter of oocytes increased from 10 microns to 84 microns with consequent increase in the follicle size from 20 microns to 320 microns. However, the diameter of oocyte did not show further increase, but the follicle size was enlarged gradually up to 500 microns. Based on the diameter of follicle and the number of granulosa cell layers, the follicle population was divisible into 5 categories: 1. primordial follicle which ranged 20 to 80 microns in diameter with few cells to one complete layer of granulosa cells in the largest cross section; 2. small follicle which was 81 to 200 microns in diameter having 2 to 3 complete layers of granulosa cells; 3. secondary or medium-sized follicle which ranged 201 to 320 microns in diameter and consisted of 4 to 6 complete layers of granulosa cells; 4. transitory follicle having diameter 321 to 360 microns and 7 complete layers of granulosa cells; 5. large sized follicle which ranged 361 to 500 microns in diameter and had more than 7 layers of granulosa cells. PMID- 2100098 TI - Information processing to rare and frequent warning stimuli in a C.N.V. paradigm. AB - Seven normal young men were submitted to standard and target paired auditory stimuli. The warning stimulus of paired tones informed subjects whether or not the impending unconditional stimulus implied a motor response. Subjects were instructed to execute the motor response at less one second after the unconditional stimulus occurrence, and were informed that the standard warning stimulus was always followed by an additional stimulus which confirmed its detection. Components of target warning and imperative stimuli responses presented a significant increase in amplitude with regard to evoked potential components elicited by standard warning and unconditional tones. P3 waves observed in response to standard warning and unconditional stimuli culminated over fronto-central cortex, while P3 of target warning and imperative tone responses peaked over centro-parietal cortex. These results suggest that manipulating warning stimulus significance by assigning to it a discriminative function, can modify processing of the information carried out by paired stimuli. PMID- 2100099 TI - In vitro effect of 4-amino-5-imidazole-carboxamide-phosphate (AICA-P) on the enzyme activity and expression of superoxide dismutase. AB - Antioxidant effects of a newly developed hepatoprotective agent 4-amino-5 imidazole-carboxamide-phosphate (Aica-P) were studied in an in vitro test system using isolated peripheral blood cells from patients with chronic alcoholic liver disease and from healthy controls. In vitro incubation with the drug in a concentration corresponding to the usual therapeutic dosage enhanced the superoxide dismutase (SOD) activity of erythrocytes and lymphocytes and also increased the superoxide dismutase expression on lymphocytes. These results indirectly suggest that antioxidant capacity may be one of the important factors in the mechanisms of hepatoprotective action of the imidazole derivate Aica-P. PMID- 2100100 TI - Role of photoperiod and temperature in production of the oestrus-inducing pheromone in male wild mice. AB - Ninety adult males divided in six equal groups were exposed to different photoperiods for 21 days. Exposures included natural light (ca 11 hr), long photoperiod (16L:8D) and short photoperiod (8L:16D). The first three groups received these exposures at room temperature (13-20 degrees C) while the remaining three at raised temperature (36-38 degrees C). Soiled bedding of the above males was introduced in the cages of unisexually housed noncyclic females and their potentiality to induce oestrus was assessed. It was noticed that the bedding of all the males proved to be a stimulus inducing oestrus in the majority of the females during the 7 day exposure. There was no significant difference in the number of females returning to oestrus following exposure to soiled bedding of different males. These results elucidate that environmental factors, especially light and temperature do not influence the production/release of the oestrus-inducing pheromone in wild mice. PMID- 2100101 TI - Effect of restriction in daily feeding periods on reproduction in the female rat. AB - Effects of restriction in daily feeding periods (2, 4, 8 and 12 hrs) imposed in 21 days old rats for 9 weeks were studied on the food intake, body growth, onset of puberty, reproductive cyclicity and ovarian functions. Control rats were feeding for 24 hrs ad lib. Though the restriction in feeding periods had no effect on the daily food intake but body growth was significantly reduced. Restricted feeding for 2, 4 and 8 hrs daily resulted in the delay in the onset of puberty, inhibition of oestrous cyclicity, reduction in ovarian weights, reduced growth, increased atresia of antral follicles and cessation of ovulation. The rats fed for 12 hrs daily, though weighed less but exhibited all the above mentioned reproductive functions similar to those of controls. The results have revealed that the restriction in feeding time induces nutritional deficiency, causing delay in sexual maturation and inhibition of ovarian functions. PMID- 2100102 TI - Effects of alternating 45-min light-dark cycles on sleep in the rat. AB - We studied the effect of alternating 45-min light-dark (L-D) cycles on sleep in rats. Introduction of short L-D cycles did not abolish the normal circadian rhythm of sleep-wake activity. The amount of non-REM sleep was however increased in the L and decreased in the D 45-min periods. REM was promoted in the D and inhibited in the L 45-min periods. The influence of L-D or D-L transitions depended on the sleep wake activity immediately before the transition. PMID- 2100103 TI - The effect of elective surgery on serum N-acetyl-beta-D-glucosaminidase activity. AB - N-acetyl-beta-D-glucosaminidase (NAG; EC 3.2.1.30) activity was measured in sera of 23 patients admitted for elective surgery. Cholecystectomy increased serum NAG activity (by 62%) (p less than 0.004), whereas other types of operations (minor or major abdominal surgery, inguinal hernias and leg varices) had no regular effect. In cholecystectomy patients, the increase of serum NAG activity was associated with parallel changes in liver enzymes suggesting that manipulation of liver may liberate NAG into the circulation. Surgical trauma per se does not provoke any significant liberation of NAG. PMID- 2100104 TI - Long-term effects of a single cadmium chloride injection on the ovulation, ovarian progesterone and estradiol-17 beta secretion in rats. AB - On the day of dioestrus II rats were given 5, 10 or 15 mg/kg of cadmium chloride (CdCl2), or 1, 0 ml/kg of 0.9% NaCl solution. Then ovarian cycle was checked daily for a period of 12 cycle length. On the day of oestrus or expected oestrus in the 13th cycle the animals were anaesthetized with pentobarbital and cannulas were inserted in one of the femoral arteries and veins and in one of the utero ovarian veins. Five-minute blood fractions were collected for 40 minutes and following the first blood samples 10 IU of hCG were injected iv. Ovarian venous outflow and blood pressure were continuously recorded. From the blood fractions progesterone (P) and oestradiol-17 beta (E2) were determined with RIA and the P and E2 secretion rates of ovary were calculated. Ovaries were excised and oviducts were flushed for counting oocytes. CdCl2 shortly after its administration induced a (dose-dependent) anoestrous period which turned into regular or irregular cycles depending on the dose. Part (28-32%) of the oestrous animals (14% that of the controls) remained unovulatory, when ovulation occurred normal number of ova was found. None of the doses of CdCl2 has influenced the blood pressure of animals and blood flow of the ovary. The basal secretion rate of P and E2 was not changed in the ovary compared to the controls. The hCG induced rise of P secretion, however, in the animals treated with 5 and 10 mg/kg bw CdCl2 was diminished and delayed, while in the animals treated with the 15 mg/kg Cd dose a complete lack of response was observed. PMID- 2100105 TI - [Tumors of the glomus caroticum]. PMID- 2100106 TI - [The immunological implications of breast cancer: the physiopathological aspects and possible therapeutic strategies in our experience]. AB - The authors, after a short review on the physiopathological patterns which regulate the function of the immunological system in patients with neoplastic disease, report their clinical prospect study, performed on a population of 71 patients affected by breast cancer. The study has the aim to demonstrate the advantage of a complete immunological monitoring, and the efficacy of a prophylactic and therapeutic treatment with thymic hormones. Results of the study can be summarized as follow: 1) very low rate of septic complications. 2) Better results as to blood cells impairement in the group submitted to both chemo- and immunotherapy. 3) In the same group, the performance status (Karnofsky index) remained above 80% in most of cases. It is underlined in this study, the hypothesis of the prognostic value pertaining to the indexes of functionality of the immune system. Authors have indeed pointed out that early metastatic spread has been observed in the two patients, treated in 1st stage with surgery and immunotherapy, but not responding with improvement of biological data. This topic has to be developed in further studies, with the aim of changing and increasing the criteria for the staging of tumors, as the authors suggest. PMID- 2100107 TI - [Primary hyperaldosteronism: our experience with 34 patients]. AB - Primary aldosteronism (PA) is a relative new endocrine disease that account for almost 1-2% of the hypertensive population. In spite of the large number of reports there is still disagreement around the preoperative diagnosis and surgical treatment. In a nineteen year period from 1970 to 1989, 34 patients came to our Department with a diagnosis of Primary Aldosteronism. 18 patients were female. Mean age at time of diagnosis was 45.5 yrs. (range 27-67 yrs.). Mean follow-up was 71 months (range 1-227 months). Follow-up was achieved in all patient. Hypertension and hypokalemia were discovered in all patients. Three patients had extremely low values of potassium and presented severe metabolic, cardiac and neurologic troubles. Localization procedure techniques improved during this period of time and at this moment CAT scan appears to be the most accurate method. Flank incision was the approach of choice in all but four patients. No postoperative complications were recorded. Histology demonstrated an incidence of adenomas according to the literature. One patient had an adrenal carcinoma with functioning metastases. He was operated on several times in order to remove the functioning node metastases but finally died with widespread disease four years after the first surgical treatment. Another patient in this series died three years after the operation for an unrelated event. In 29 patients hypertension and hypokalemia disappeared while in two patient, one with an adrenal carcinoma hypertension increased. Primary aldosteronism is a rare endocrine disorder whose incidence is increased in the last years because of the improvement in diagnostic procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100108 TI - [Laparostomy in the treatment of pancreatic abscess. A case report]. AB - Pancreatic abscess is a major cause of death from acute pancreatitis; its reported frequency is between 1.7 and 25 per cent of all patients presenting with acute pancreatitis. The mortality varies between 13 and 54 per cent. Despite apparently adequate initial surgical treatment, the recurrence rate is about 30 per cent. The key to survival in pancreatic abscess is adequate drainage of cavity. Proponents of open treatment claim that it allows better drainage of the viscid content of the pancreatic abscess which often cannot easily pass down a drain. In the present case, following laparotomy for severe intra-abdominal sepsis due to pancreatic abscess, the abdominal cavity was left open to heal by granulation. The procedure permitted early resolution of the septic process. Total parenteral nutritional support resulted in definitive wound healing. We regard laparostomy as a valuable technique in the management of pancreatic abscess; the successful of this technique hinges on expert nursing care and the capability of maintaining complication-free long term parenteral nutrition. PMID- 2100109 TI - [Laparocele: a review of the literature and analysis of case histories]. AB - We analyze a group of 64 laparoceles from which it emerges a per cent distribution in the different regions and a correlation between the dimensions of the lesion and the relative regions in agreement with the data usually given in the literature. Furthermore we point out a clear dependence on pathogenetic factors of general and local order. Is therefore recognized the necessity of preventing their insurgence and reducing the risk of relapses through appropriate laparotomy incisions, with adoption of a suitable surgical technique and the correction of systemic diseases. The voluminous laparoceles are responsible of cardiac, respiratory, coagulative diseases, that must be scrupulously judged for an appropriate therapeutical approach. The surgical treatment, as well as for the cases of bigger dimensions, has mostly availed itself of an elementary technique (simple approach, apposition "en paletot" splitting of the fasciae). In the necessity of strengthening weak parietal tissues or of replacing vast losses of matter, we have limitedly resorted to autologous grafts, while good results have been observed with the lyophilized dura mater. PMID- 2100110 TI - [Intestinal tuberculosis--a clinical case]. AB - The intestinal tuberculosis is a rare disease in Europe and in North America. It is an important disease because some patients can develop intestinal stricture or subacute intestinal obstruction and, sometimes, tuberculous peritonitis. It is often difficult differentiate intestinal tuberculosis from Crohn's disease or intestinal tumors. The treatment is controversial and may be medical or surgical, but the response to medical therapy is not clear, especially in complicated disease. The authors report a case of ileal tuberculosis treated with surgical therapy. PMID- 2100111 TI - [Low anterior resection in the curative surgical treatment of rectal cancer]. AB - Abdominoperineal resections for rectal cancer are being performed with decreasing frequency in favour of sphincter-saving resections. It remains to be demonstrated that sphincter preservation has not resulted in compromised local disease control, disease-free survival and survival. For this purpose 315 patients with rectal carcinoma have been studied. In 44 cases (13.9%) it was only possible to perform a colostomy; a curative resection has been carried out in 206 (65.3%). Sphincter-saving procedure was performed whenever possible: the length of margin of resection was at least 2 cm. The operation were: 61 abdominoperineal excisions (AP), 135 anterior resections (AR), 10 transanal excisions (excluded from this analysis). The distribution of tumors in the various Duke's stages was: Dukes A- 28 patients, Dukes B--143, Dukes C--35. The thirty-days mortality was 6 patients (9.8%) for AP and 6 (4.4%) for AR. Local recurrence was: AP 9 cases (16.1%), AR 16 cases (12.4%); for tumors 4-8 cm from anal verge recurrence was 18.7% for AP, 17.1% for AR. Concerning staging, local recurrence was more common in the Dukes C stage (36%) than in the Dukes B (11.2%) or in the Dukes A (3.7%). 5 years survival after AP was 54.6 percent and after AR 57.9 percent. Concluding, in our experience, there was no significant relationship between local recurrence or survival and type of curative surgery (AP or AR). Local recurrence and survival were only related to tumor stage (p less than 0.01): lateral tumor extension in these advanced and aggressive lesions appears to be the major determinant of local recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100112 TI - [The termination of the superior hemorrhoidal artery. An anatomicoradiological study]. AB - The author report the observations carried out on the distal part of the hemorrhoidal artery, obtained with a research on the vascularization of the large intestine, studied by the angiographic method and injection of the c.m. in the anatomical specimen immediately after surgical extirpation. The study was based on 92 anatomical specimens and reveals a variability of the terminal arterial distribution which can be summarized in few more frequent models, but cannot be given an absolute rule. PMID- 2100113 TI - [The endoscopic diagnosis of rectorrhagias]. AB - The diagnosis of bleeding of gastrointestinal low tract is still a very controversial subject. At the Service of Digestive Endoscopy of Popoli (PE) Hospital, in a period of 4 years, 2074 colonoscopies have been effected. In 640 cases, that is 30.8%, the indication for the exam was suggested by rectal bleeding. In the 566 patients examined for minor rectal bleeding, the most frequent lesions were: haemorrhoids (35.3%), polyps (15.2%), malignant neoplastic disease (9.3%). In all active rectal haemorrhages (14 massive, 41 medium) an urgent colonoscopy has been carried out with a percentage of success of 90%; in the 20 cases of unexplained melena, colonoscopy has not led to a diagnosis; in the 14 patients with unexplained anemia, colonoscopy has shown 2 carcinomas, whereas in the 5 cases with occult blood in stools it has been diagnostic in the percentage of 60%. We have ascertained that, when barium enema was effected before colonoscopy, the diagnostic agreement between the two examinations was only of 21.4 (9/42); on the contrary there was an agreement of 95% when colonoscopy was effected before barium enema. In accordance with Siewert and Blum (25), Ottenjann (24) and Farrands (42), we believe that colonoscopy should be considered the main examination after either major or minor rectal bleeding, because it is a quick and safe investigation with high diagnostic specificity and sensitivity. We refuse William's position (41), because, even in presence of haemorrhoids or anal fissures, the colon must be studied as a whole, especially in a period when neoplastic disease of this tract of intestine is considerably increasing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100114 TI - [Age as a prognostic factor following excisional surgery for colorectal cancer]. AB - On a series of 369 patients with colorectal cancer who underwent curative resections at the I Instituto di Clinica Chirurgica della Universita "La Sapienza" of Rome between 1960 and 1980, age was related to survival. All patients were followed for a minimum of ten years; 79 of them were aged over 65 years and 290 under at the time of the operation. The survival was correlated to the age and to other prognostic parameters: post surgical stage (TNM UICC classification) degree of differentiation of the tumour (NG--Black classification), degree of lymphocytic infiltration of neoplasm (LI Black classification) as expression of immunological immune-response of the host. Patients less than 65 years old had a better survival than patients greater than = 65 years old (median survival 72 months and 44 months respectively) (p = 0.006). These differences where true in subgroups with stage 2 of disease (p TNM UICC) and a favourable immunological reactivity (LI greater than = 2). These results suggest a possible independent role of age in defining the outcome of patients with colorectal cancer. PMID- 2100115 TI - [Leydig-cell tumors of the testicle]. AB - Leydig's cells tumor account for 1-2% of all testicular tumors. The authors report a rare case of benign Leydig's cells tumor in a young man with gynecomastia. They examine the embryogenesis, the hormonal modifications, the criteria of malignancy, the treatment and results. They present a review of the literature pertaining to this rare tumors. PMID- 2100116 TI - [Acute pancreatitis: biochemical estimation of the prognosis]. PMID- 2100117 TI - [Computed tomography in acute severe pancreatitis]. PMID- 2100118 TI - [Acute pancreatitis: treatment]. PMID- 2100119 TI - [Surgical treatment of gastroesophageal reflux by modified Hill's posterior cardiopexy. Apropos of 441 cases]. AB - Between 1972 and 1986, 490 modified Hill's procedures were performed for gastro esophageal reflux; 441 cases were retrospectively studied consisting of 245 males and 196 females, aged from 4 days to 83 years, with a mean age of 41 years. Average duration of gastrointestinal symptoms was 5.4 years. The proposed technique is described, allowing cardiopexy without intraoperative manometry. Mortality was 1.4% (6 cases); one death was due to surgery. Morbidity was 5.4% (24 cases). With a mean follow-up of 5.2 years, a clinical cure was obtained in 93.5% of cases. Causes of failures were analyzed: the only possible pre-operative factor was the presence of peptic stenosis. Pylorospasm appeared to be a post operative cause of failure. The 28 patients for whom surgery failed were medically treated (18), dilated (5) or reoperated (5). Three new cardiopexies and 2 fundoplications cured the last 5 patients with a mean follow-up of 5.8 years. Recurrences of symptoms and discoveries of failure were generally detected early after the operation: 20 before 6 months (71%), 1 between 6 months and 1 year, 2 between 1 and 2 years, 3 between 3 and 4 years, 1 between 4 and 5 years. PMID- 2100120 TI - [Solitary rectal ulcer syndrome: clinical features, clinical course and treatment. Apropos of 22 cases]. AB - Rectopexy associated with anterior prolepsectomy was performed for 22 patients (19 females, 3 males), with solitary rectal ulcer syndrome (SRUS) surrounding internal rectal prolapse. The different lesions of SRUS were distributed among 3 main groups (G) according to the macroscopic appearance: G1: solitary ulcer (n = 7); G2: ulcerated proctitis (n = 7); G3: muco-hemorroidal prolapse (n = 3). A significant difference (P less than 0.05) was observed between each group, concerning mean age (G1: 34 years, G2 = 49, G3: 65) and the degree of perineal descent, which was more important in G3 and G2. Posterior intersphincteric rectopexy was performed for 6 patients in G3, with descending perineum and faecal incontinence, treated in the same time by perineoplasty (Parks). Abdominal rectopexy, mainly by the antero-posterior technique (Nicholls), was performed for the other patients (n = 6). Large anterior prolapsectomy reaching the top of the mucosal prolapse (4-7 cm), allowing ulcer resection in 3 cases, was combined with rectopexy. Associated operations were: sphincterotomy (n = 8) for narrow fibrous anal canal, sigmoidectomy (n = 4) for dolichocolon. Mean healing time for the solitary ulcer group (G1) was 2 months, 1 month for lesion of G2 and G3. Failures concerned 1 solitary ulcer after abdominal rectopexy and 1 ulcerative proctitis after rectopexy without prolapsectomy. Anorectal pain (81%), rectal bleeding (76%), faecal incontinence (27%), straining (81%), were cured or improved in 80% of cases. These results tend to confirm the efficacy of rectopexy, specially using the antero-posterior technique, for the treatment of SUSR with internal rectal prolapse. Nevertheless, rectopexy seems to be insufficient to correct the mucosal component of internal rectal prolapse, bearing the ulcerated lesion which needs to be treated by associated anterior prolapsectomy. Similarly all functional or organic disorders involving the perineum, anal canal or colon leading to anorectal dysfunction must also be considered to ensure complete treatment. PMID- 2100121 TI - [Endoscopic treatment of vesicorenal reflux in children. Review of three years experience and prospects for the future]. AB - Endoscopic injection of teflon paste, used since 1984, represents an alternative to the surgical treatment of vesico-renal reflux. The success rate varies from 75 to 89% after a single injection and from 85 to 95% after two injections, according to the teams. The results are less satisfactory for the high grades and for refluxes on duplicity (25 to 45% failure rate). This technique is particularly attractive in the case of a difficult surgical intervention, notably when a reimplantation has failed, in the case of reflux on neurological bladder, urethral valves or exstrophy. Various causes of failure or relapse are considered. The advantages of the technique are obvious (low morbidity, very short hospital stay) and surgery is always possible in the case of failure. After one or two years, the reflux reappears in 2 to 9% cases. Long term results cannot be assessed as the follow-up period is too brief at the present time. For this reason, and although the endoscopic and surgical findings are reassuring, tolerance to teflon both locally and at a distance requires confirmation and other products such as collagen are now being used. PMID- 2100122 TI - [Has the Ilizarov technique come of age in pediatric orthopedics?]. AB - The Ilizarov method can be used for several applications: limb lengthening correction of axial malignement, pseudarthrosis, traumatology and in several sites: leg, foot, knee, femur, forearm and arm. The authors recall the principles and possibilities of this method and give details about its utilisation for each indication, and for their preferred indications: lengthening for marked disparity, complex trauma, progressive distraction of soft tissues, and for very young children. PMID- 2100123 TI - [Rectal resection with colo-anal anastomosis for ergotamine-induced rectal stenosis]. AB - Anorectal ulcers due to ergotamine suppositories are extremely rare. We report the first case of rectal stenosis following regular abuse of ergotamine suppositories which required rectal resection and coloanal anastomosis, despite stopping the intoxication 1 year previously. The rectal eversion during the perineal procedure allowed a low anastomosis to be performed, on the dentate line. One year later, the functional result was considered to be good, demonstrating the place of coloanal anastomosis in benign rectal pathology. PMID- 2100124 TI - Incidence rate of hepatitis B: results of a record linkage study among healthy Korean males. AB - A stable, liver disease-free cohort of 369,725 was reconstructed as of 1984 for the study of hepatitis B virus seromarkers and liver diseases. The cohort consisted of male beneficiaries of the Korea Medical Insurance Corporation (KMIC) over 30 years of age and living nationwide. Subjects who were both negatives for HBsAg and anti-HBs (N = 274,037) were selected for incidence of hepatitis B. Data on test results of HBsAg and anti-HBs in 1984 and on hepatitis B occurrence during 1985-1986 were collected from the files of the KMIC. Linkage was done between these two data sets to measure the incidence rate through a longitudinal observation of the male population. Correction against misclassification error and duplicate claims was done by a sample survey and verification procedures. The incidence rate of hepatitis B was 17.13 per 100,000 person-years for acute viral hepatitis B and 15.74 for chronic hepatitis B, respectively. An increasing age dependent pattern for acute hepatitis B was not so prominent in this population. However, the incidence rate of chronic hepatitis B steadily increased with age. The relative risk, estimated by a log-linear model for rate and constant hazard, was significantly higher in the over-60 age group than in the others. The incidence rate in the lower socioeconomic class was higher than in the others, although statistically not significant. PMID- 2100125 TI - Differential application of rate and delta check on selected clinical chemistry tests. AB - Through the present delta value check used in quality control programs is a powerful tool for detecting random errors in clinical chemistry analysis, it has some problems, such as missed true errors and delays in reporting time, because it also has the potential of showing erroneous positive results. Recently, new calculation methods for delta check with delta difference, delta percent change, rate difference, and rate percent change have been suggested by Lacher and Connelly (Clin Chem 34:1966-1970, 1988). Based on this new delta check method, we made the new criteria of which calculation method is applied to the clinical chemistry tests, i.e., the differential application of rate and delta check, and selectively applied the new method to 17 chemistry tests in order to solve the above problems. The applied criteria were the time dependence of the test item and the coefficient of variation of the absolute delta difference. Calcium, inorganic phosphorus, total protein, albumin, sodium, potassium, and chloride were classified as delta difference calculation method group; glucose and cholesterol as delta percent change group; creatinine, total and direct bilirubin as rate difference group; and urea nitrogen, uric acid, ALP, ALT, and AST as rate percent change group. With the previous criteria by Whitehurst et al. (Clin Chem 221:87-92) for 5045 specimens, the check-out rate was 47.8% (2,411 out of 5,045), and the positive predictive value was 0.41% (10 out of 2,411). For the new criteria, the check-out rate was 12.7% (621 out of 5,045), and the positive predictive value was 1.8% (nine out of 621).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100126 TI - Neoplastic Paneth cells in the experimental murine carcinoma of the small intestine. AB - The purpose of this study is to elucidate the participation of Paneth cells in experimentally induced adenocarcinoma of the intestine. The rats were fed with N methyl-N'-nitro-N-nitrosoguanidine (MNNG) dissolved in drinking water ad libitum at a concentration of 100 micrograms/ml for 28 weeks. They were sacrificed 12 weeks after the last MNNG administration. A number of tumor cells containing large eosinophilic granules in their supranuclear cytoplasm (Paneth cells) were observed in about 20% of the experimentally induced adenocarcinoma of the small intestine. The granules were stained positively with Lendrum, periodic acid Schiff, Masson's trichrome, and Mallory's phosphotungstic acid hematoxylin. Ultrastructurally, the granules were round, osmiophilic, and relatively even in size. We compared the morphologic features of the Paneth cell-containing small intestinal adenocarcinomas (Group I) with those without Paneth cells (Group II). Group I was distinguished from Group II by its better differentiation, larger tumor size and lower incidence of calcification. Although Paneth cells are extremely rare in human gastrointestinal carcinomas, twenty percent of MNNG induced intestinal carcinomas harbor Paneth cells. The neoplastic Paneth cells in experimental carcinomas may differentiate from uncommitted cells in the deeper portion of the crypt. PMID- 2100127 TI - Lobar agenesis of the left upper lung--a case report. AB - Lung agensis is a rare developmental anomaly. It can range from total bronchial and parechymal agensis to mild pulmonary parenchymal hypoplasia of one or both lungs. A case of lobar agenesis of the left upper lung in a 15-year-old boy is presented. The patient had mild exertional dyspnea. Pulmonary angiography revealed the absence of the left upper pulmonary artery and vein. Bronchography showed no branching of bronchus to the left upper lobe. Intravenous pyelography revealed incomplete duplication of the right urinary tract. PMID- 2100128 TI - Fibrous hamartoma of infancy manifested as multiple nodules--a case report. AB - Fibrous hamartoma of infancy is an uncommon benign fibrous proliferation, usually presenting as a solitary nodule. A rare example of multiple fibrous hamartoma of infancy is described. Two masses which developed in the upper arm of a 10-month old boy were successfully excised, and one month later three small nodules 2 cm below the previous operation field appeared. It will be further elucidated whether multiple forms and early recurrence are related or not as cases accumulate. PMID- 2100129 TI - [Migraine and cerebral infarction]. PMID- 2100130 TI - [Hormonal profile and changes in platelet aggregation in menstrual migraine]. AB - We evaluated the hormonal profile and the platelet function in a group of 20 patients with menstrual migraine and a control group of 10 healthy women. Plasma levels of estradiol, progesterone, FSH and LH, as well as betathromboglobulin, platelet factor 4 and platelet serotonin were measured in different phases of the menstrual cycle. The hormonal profile did not show significant differences between both groups. The patients with menstrual migraine had higher BTG, FP4 and serotonin levels in the premenstrual phase than the control group. The results of this study show that in premenstrual migraine a platelet hyperagregation develops during the premenstrual phase. This abnormality is not directly correlated with the hormonal fluctuations observed during the menstrual cycle. PMID- 2100131 TI - [Evaluation of respiratory muscle function (maximal respiratory pressures) in myasthenia gravis]. AB - In myasthenia gravis (MG) the status of respiratory function has a paramount importance and a careful evaluation is recommended. The weakness of respiratory muscles has been demonstrated in several studies. However, a reliable simple method for the evaluation of this muscular group was lacking until recently, when the usefulness of the maximum respiratory pressures, expiratory (MEP) and inspiratory (MIP), was demonstrated. We evaluated with this method a series of 23 patients with a diagnosis of MG (16 females and 7 males), with a mean age of 46 years (22-68 years), clinically stable and without symptomatic dyspnea. They were distributed in: grade I (5), grade II A (12), and grade II B (6). All of them were evaluated with flow-volume curves, pletysmography, gas transfer, MEP and MIP. The resulting values were then correlated with the expected ones, a reduction greater than one SD being considered as abnormal. The results showed that respiratory function was normal without a restrictive pattern. However, the force of respiratory muscles was reduced in the following proportions of patients in the different groups: grade I: MIP 40%, MEP 60%; in grades II A and II B both MEP and MIP were reduced in 84% of patients. When a statistical comparison with the expected values was carried out it was found that MEP and MIP, considered as a group, were reduced to 53% of the expected values (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100132 TI - [Lyme borreliosis: neurologic manifestations]. PMID- 2100133 TI - [Conduction aphasia. Neuropsychologic study of a patient]. AB - We report a patient with clinical features consistent with conduction aphasia. The patient had dilated cardiomyopathy, and as a complication, had cerebral infarction one year before neuropsychiatric evaluation. His language was fluid, paraphasic, with a "phonetic approximation behavior" in an attempt to pronounce the adequate word. Comprenssion was normal and repetition difficult, with numerous paraphasias. Number repetition was particularly affected. Reading and writing had the same features as spontaneous language. In association with the language disorder, he had "aphasic" acalculia, but other signs of left parietal involvement were absent. Magnetic resonance images showed a low parietal small chronic ischemic area, which also involved the left infrasilvian region, both in the cortex and in the white matter, presumably in the arcuate bundle. The differential diagnostic difficulties of this condition are discussed from a behavioral standpoint. PMID- 2100134 TI - [Wilson's disease: computed tomography and magnetic resonance imaging]. AB - Wilson's disease is an autosomal recessive hereditary disease in which the capacity of biliary copper excretion is reduced, resulting in a toxic accumulation of this metal in the liver, brain and other organs. The neuroimaging techniques, computed tomography (CT) and nuclear magnetic resonance (NMR), have been incorporated to the diagnostic workup in patients with suspected Wilson's disease (WD). We report two patients with WD in whom CT and NMR were carried out for the evaluation of the central nervous system (CNS). The lesions appeared as hypodense areas in CT or signal abnormalities in NMR over the involved structures: putamen, caudate nucleus, cerebellar dental nucleus, red nucleus and subcortical white matter. In one of the patients, hypointense signal areas were found over both putamen nuclei in T-2 times of NMR, which might correspond to cavitary necrosis or copper deposition. The lesion distribution suggests that vascular lesions might play a role in the mechanisms of tissue damage. These findings show that CT and NMR are very helpful to evaluate WD. NMR images are quite characteristic of this disorder. PMID- 2100135 TI - [Inflammatory signs as a histological finding in oculopharyngeal dystrophy]. PMID- 2100136 TI - [Diffuse intraspinal hemorrhage as a complication of anticoagulant therapy]. PMID- 2100137 TI - [Syringomyelia, posterior fossa cyst and acute respiratory distress]. PMID- 2100138 TI - Compassion as power: clinical implications of therapeutic touch. PMID- 2100139 TI - The endogenous healing process. PMID- 2100140 TI - Rogers' Science of Unitary Human Beings and Jonas' Philosophy of Organism. PMID- 2100141 TI - Assessment of the unitary human being: one clinician's dilemma. PMID- 2100142 TI - Knowing participation in the parent-infant mutual process. PMID- 2100143 TI - Microdensitometer-computer correlation analysis of two distinct, spatially segregated classes of microtubule bridges in Allogromia pseudopodia. AB - Previous video-light microscopic studies have shown that the microtubule bundles in the pseudopodia of foraminiferan protists display several types of movements in vivo, including active bending, zipping/splaying, and axial translocations. To gain insight into the types and arrangement of microtubule-associated proteins (e.g., mechanoenzymes, crosslinkers) in such a highly dynamic system, we employed microdensitometric-computer correlation methods to analyze, quantitatively, intermicrotubule bridges in thin-section electron micrographs of Allogromia laticollaris and Allogromia sp. (strain NF). Two distinct bridges occupying mutually exclusive zones between adjacent microtubules were identified. Type I bridges displayed a single axial repeat (34 nm for A. laticollaris and 28 nm for Allogromia sp.) and Type II bridges showed a typical 12-dimer helical superlattice pattern. In A. laticollaris, the two types of bridges were morphologically distinct: Type I bridges were aligned perpendicular to the microtubule wall and were 23-nm wide with an electron-lucent core; Type II bridges were irregular filaments projecting from the microtubules at various angles. When compared with the known distribution of microtubule-associated proteins in other systems, our findings indicate that, in vivo, Allogromia pseudopodial microtubules are decorated with MAP2-like bridges interrupted by discrete clusters of a dynein-like component. PMID- 2100144 TI - Phase diagram of lipid A from Salmonella minnesota and Escherichia coli rough mutant lipopolysaccharide. AB - We have reported here on the structural polymorphism of lipid A, the "endotoxic principle" of bacterial lipopolysaccharide. For lipid A of rough mutant lipopolysaccharide from Salmonella minnesota and Escherichia coli, the three dimensional supramolecular structures were determined with x-ray diffraction utilizing synchrotron radiation. The investigations were performed in the water concentration range 10 to 95% by weight, at [lipid A]:[Mg2+] molar ratios from 1:0 to 0.1:1, and in the temperature range from 20 to 70 degrees C. These data were correlated with measurements of the beta----alpha phase behaviour which was monitored with differential scanning calorimetry and Fourier-transform infrared spectroscopy. We found that the transition temperature of the acyl chains ranges- in the absence of Mg2(+)-from 45 degrees C at high to 56 degrees C at low water content, and-at an equimolar content of Mg2(+)-from 52 degrees C at high to 59 degrees C at low water concentrations. In the gel phase-in which the lipid A acyl chains are more disordered than those from saturated phospholipids-cubic phases are adopted at high water content (greater than 60%) and at high [lipid A]:[Mg2+] molar ratios. At low water contents, lamellar states are assumed exclusively. In the liquid crystalline state of lipid A, the hexagonal HII state is adopted under all conditions. The structural variability of lipid A is highest at high water concentrations, and structural changes may be induced by only slight changes in temperature, water content, and Mg2+ concentration. Under physiological conditions, however, the lipid A assemblies exhibit a strong preference to cubic structures. PMID- 2100145 TI - Secondary lysosomes as an integral part of the cytoskeleton: a morphological study in rat Kupffer cells. AB - Rat Kupffer cells contain the three major cytoskeletal components: microfilaments (MF), microtubules (MT), and intermediate filaments (IF) of the vimentin type. Previous cytomagnetometric data obtained from alveolar macrophages and rat Kupffer cells in culture provided evidence that actin filaments contribute to the movements of lysosomes. The lysosomal transport in living cells was affected, when the MFs were selectively disturbed, whereas the depolymerization of the MTs had no effect on the lysosomal movement measured by cytomagnetometric means. Immunofluorescence and ultrastructural studies of isolated and cultured rat Kupffer cells, presented in this paper, will investigate the relationship between lysosomes and the cytoskeleton. The principal filamentous structure in the peripheral cytoplasm of Kupffer cells in a dense meshwork of actin filaments. The dimension of the meshes combined with the dimensions of lysosomes implies the necessity of either (i) disintegration of the actin filament cross-links, (ii) depolarymerization and redistribution of MF's, or (iii) a displacement of actin filaments by the lysosomes during the organelle transport. The presence of microtubules in cytoplasmic protrusions and their track from the periphery to the perinuclear region during interphase might play a role in the transport mechanism of lysosomes, the more so because microtubules could often be demonstrated in closest association with lysosomes even in the first phase of endocytosis. The distribution pattern of vimentin, found as a dense interconnected framework surrounding the lysosomes like a basket, could play a role in positioning the organelles. The dynamic functions of MF's and MT's and their multifunctionality led to an adaptive and flexible organization of these filaments which may both be involved in lysosomal motion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100146 TI - Laser confocal scanning microscopy of the surface membrane/T-tubular system and the sarcoplasmic reticulum in insect striated muscle stained with DilC18(3). AB - The structure of the surface membrane/transverse tubular (T-tubular) system and of the sarcoplasmic reticulum (SR) of the labial adductor muscle of the honey bee (Apis mellifera) was examined by laser confocal scanning microscopy, after staining with the fluorescent membrane probe DiIC18(3). The following components of the surface membrane/T-tubular system were visualized: transverse tubular networks that are located in the A-band close to the A-I junction and form dyads with the SR, longitudinal tubules that link the T-tubular networks within the between sarcomeres, and surface invaginations of larger diameter that contain tracheoles. The well developed SR forms a dense network of branching and anastomosing tubules in the A-band. A few tubular elements in the interfibrillar space in the I-band link the SR of adjacent sarcomeres. This study demonstrates the advantages of the laser confocal microscope and lipophilic fluorescent dyes for studying the 3-D structure of cellular membrane systems. PMID- 2100147 TI - Dermal collagen fibrils are hybrids of type I and type III collagen molecules. AB - It has been suggested that dermal collagen fibrils with 67-nm periodicity consist of hybrids of type I and type III collagens. This is based on the assumption that all these banded fibrils are coated with type III collagen regardless of their diameter. However, conclusive evidence for this form of hybridization is lacking. In order to clarify this problem dermal collagen fibrils were disrupted into microfibrils using 8 M urea. Single and double indirect immunoelectron microscopy showed type III collagen at the periphery of intact collagen fibrils but no labeling with type I collagen antibodies, suggesting that the epitopes for this collagen were masked. Disrupted collagen fibrils revealed type I collagen throughout the fibril except for the periphery which was coated with type III collagen. Almost no type III collagen was noted in the interior of the collagen fibrils. Since type III collagen is present only at the periphery it suggests that this collagen has a different role than type I collagen and may have a regulatory function in fibrillogenesis. PMID- 2100148 TI - Fusion between myogenic cells in vivo: an ultrastructural study in regenerating murine skeletal muscle. AB - Fusion of myogenic cells in adult murine skeletal muscle regenerating in vivo was examined at the ultrastructural level. Fusion of myoblast to myoblast, myoblast to myotube, and myotube to myotube was observed by 4 to 5 days after injury. Fusion between myogenic cells (myoblasts or myotubes) lacking a definitive glycocalyx or external lamina (basal lamina) occurred at multiple sites. It was defined by zones of cytoplasmic confluence between apposed cells at sites where contiguous segments of the cell membranes were interrupted while their edges had united resulting in linear continuity; vesicles of varying dimensions were frequent in these areas of fusion. Myoblasts were seen invaginating the surface of myofibres and again vesicles were seen in abundance in such regions. Cilia were often observed at this junctional zone suggesting that they might play a role in fusion. In the one example of probable fusion between a myotube and a myofibre, only a single area of cytoplasmic continuity was apparent. PMID- 2100149 TI - Intracellular localization of titanium within xenografted sensitive human tumors after treatment with the antitumor agent titanocene dichloride. AB - In the present study, the intracellular localization of titanium was analyzed in three xenografted human adenocarcinomas of the colon sigmoideum (S 90), the stomach (M-Stg 4), and the lung (L 261) in dependence on the time after application of a single therapeutic dose (80 mg/kg) of the organometallic antitumor agent titanocene dichloride (C5H5)2TiCl2. The investigations were performed by use of electron energy loss spectroscopy (EELS), a method which allows microanalysis in ultrathin sections, in combination with electron spectroscopic imaging (ESI), which offers the possibility to image the two dimensional localization and distribution of light- and medium-weight elements in animal tissues. In all three tumors which were studied, titanium was at first detected within the nucleus and, some hours and days later, it was additionally found in cytoplasmic lysosomes. In the colon and lung tumors S 90 and L 261, already 12 hr after treatment, titanium was traceable as tender granules in the nuclear chromatin. During the following days, it was then accumulated in certain areas of the nuclear heterochromatin and, in the case of the L 261 tumor, also in the nucleolus. Maximum concentrations were attained in the nuclei and nucleoli at 48 hr after substance application. Thereafter, titanium was increasingly incorporated into cytoplasmic lysosomes which are known to be involved in intracellular degrading and digesting processes and which occurred in increased numbers in treated tumor cells. Regarding the stomach carcinoma M-Stg 4, titanium was recognized in the nuclear heterochromatin only 1 and 2 days after application of titanocene dichloride. At 48 hr, it was additionally detected in cytoplasmic lysosomes. In all cases where titanium was found accumulated in the nucleus and in lysosomes, phosphorus was simultaneously enriched in a similar local distribution and a concentration which even exceeded that within phosphorus-rich areas, e.g., the nuclear heterochromatin and cytoplasmic ribosomes. These results confirm a primary interaction of titanium-containing metabolites deriving from titanocene complexes with nucleic acid molecules, especially with nuclear DNA. They suggest the formation of aggregates between nucleic acids and titanium containing metabolites which are obviously extruded out of the nuclei and incorporated into cytoplasmic lysosomes, known to be involved in intracellular digesting processes. PMID- 2100150 TI - Imaging cells with the atomic force microscope. AB - Different types of cells have been imaged with the atomic force microscope. The morphology of the archaebacterium Halobacterium halobium in its dry state was revealed. On a leaf of the small Indian tree Lagerstroemia subcostata a stoma was imaged. The lower side of a water lily leaf was imaged in water showing features down to 12 nm. Finally, fixed red and white blood cells were imaged in buffer showing features down to 8 nm. The images demonstrate that atomic force microscopy can provide high-resolution images of cell surfaces under physiological conditions. PMID- 2100151 TI - Polymerizing properties of pepstatin A. AB - Pepstatin A, a pentapeptide aspartyl protease inhibitor, can spontaneously polymerize into filaments having a helical substructure and, after negative staining, characteristic diameters ranging from 6 to 12 nm. Optical diffraction analysis demonstrated that these filaments consist of a 6-nm-wide strand helically wound with a periodic pitch of 25 nm. Selected images suggest that these filaments may actually be composed of two, intertwined 6-nm-wide strands, an hypothesis not at variance with the diffraction data. These filaments may extend over several micrometers. At low ionic strength and neutral pH, the critical concentration for pepstatin A filament assembly is 0.1 mM. At higher pepstatin A concentrations or in physiological salt solutions, a variety of higher order structures were observed, including ribbons, sheets, and cylinders with both regular and twisted or irregular geometries. Pepstatin A polymerized into these higher order structures loses its ability to inhibit the aspartyl protease of the human immunodeficiency virus type 1. These results have implications not only for model studies on the polymerization of small peptides into higher order structures, but also for the practical development of soluble protease inhibitors. PMID- 2100152 TI - Prognostic criteria in haemorrhagic stroke with good outcome potential. AB - 168 patients with haemorrhagic stroke (H.S.) were clinically and paraclinically studied. In 74 (44%) patients, the outcome was favourable whereas 94 (56%) died. The prognostic criteria were assessed according to: location and size of haematoma, consciousness vegetative disorders, medical history, comorbidity, pupillary and oculomotor disturbances. PMID- 2100153 TI - [Lengthening of the latency of the secondary components of the VEP in high lesions of the brain stem]. PMID- 2100154 TI - Assessment of various psychopharmacological combinations in the treatment of presenile and senile primary degenerative dementia. AB - The effects of various psychopharmacological combinations were used in a sample of 90 patient fulfilling the DMS-III criteria for presenile or senile primary degenerative dementia divided into 3 equal subgroups. Regardless of the drug combination used, an improvement of verbal test performances was noticed. PMID- 2100155 TI - Psychosocial factors implied in the onset and clinical picture of the primary affective disorders. AB - The present study is aimed to investigate the psychosocial factors acting on the individual, at the onset of depressive and/or manic episodes in primary affective disorders. Attention has been paid to the specific influence on the clinical picture, evolution and implicitly on the therapy of the disease. PMID- 2100156 TI - Multiple sclerosis associated with axonal neuropathy. PMID- 2100157 TI - [The meningo-encephalo-myelo-polyradicular form of Behcet's disease. An anatomicoclinical case]. PMID- 2100158 TI - Nonclinical study requirements for ophthalmic drugs and devices in the United States. AB - The eye is a unique organ embryologically, immunologically, physiologically and consequently exhibits unique toxicological responses. Toxic responses in the eye may result from topical ocular administration of drugs, intraocular administration or implantation of drugs or devices or may be the result of target organ toxicity following systemic administration of a drug. The primary responsibility of the toxicologist is to establish the safety/toxicity profile for a drug or device under development and thus provide an appropriate risk analysis of the drug/device for human use. For the ophthalmic toxicologist this safety profile must include the appropriate toxicological evaluations to place in perspective the intended use of the drug or device, its effect on the relevant ocular tissues, its potential for adverse systemic effects, if warranted, and the potential risk to the patient in the clincal setting. PMID- 2100159 TI - Requirements of preclinical examinations. AB - The eye is an important and sensitive target organ not only for ophthalmic drugs but also generally for adverse drug effects and has to be taken into consideration accordingly when performing toxicological studies. Depending on the drug in question protocols for oculotoxicity studies have to be determined on a case by case basis. The test battery used to detect possible eye damage should be an intelligent combination of pharmacokinetic/metabolic studies, clinical examinations, pathomorphologic examinations, and biochemical tests. For special studies on oculotoxicity only pigmented animals should be used. The legal basis for the necessity to conduct oculotoxicity studies and ophthalmologic examinations in toxicity studies is given by national law (AMG) and guidelines and by EEC-Guidelines. Studies have to be performed according to the principles of Good Laboratory Praxis. PMID- 2100160 TI - Albino versus pigmented animals for ocular toxicity testing. AB - The capability of uveal and retinal tissue to accumulate exogenously administered materials, coupled with the existence of anatomic, physiologic and biochemical ocular abnormalities in albino animals, evokes the question of whether albino animals are suitable for testing novel compounds for untoward ocular effects. Examples of special susceptibilities of either pigmented or non-pigmented animals to novel compounds exist. The best way to avoid unanticipated oculotoxic effects from the administration of novel compounds is to use both pigmented and unpigmented strains. PMID- 2100161 TI - Cytotoxicity studies in ophthalmology. AB - Ocular tissues and cells are more and more in direct contact not only with drugs but also with biomaterials, such as contact lenses, intraocular implants, corneal shields, and the cell reactivity study is an indispensable step before any clinical and human utilization. The cell toxicity may be direct, by cell membrane damaging, metabolic disturbance, or indirect by mitosis or cell differentiation blocking. In order to evaluate the unwanted effects, cell cultures are performed according to the drug or to the biomaterial to be tested: conjunctival and corneal epithelial cells, lens epithelium, ciliary processes epithelium... In this report, the cytotoxicity of three substances were evaluated on corneal cultured cells: Benzalkonium chloride (BAK), an ophthalmic preservative; Novesine (Oxybuprocaine + BAK), local anaesthetic; Neosynephrine (Phenylephrine chlorydrate), a commonly used mydriatic in ocular surgery. Results of cell counting (cell viability) are given according to curves and histograms (percentage of dead cells depending on time and doses). These data are discussed according to the different mechanisms of action of the three drugs BAK and Oxybuprocaine were found to exert a more direct cell toxicity whereas phenylephrine chloride acted indirectly by causing the sloughing of the cell monolayer. PMID- 2100162 TI - Biophysical methods to monitor lens aging and pre-cataractous changes in vivo. AB - When monitoring for drug induced lenticular side effects and/or anti-cataract drug efficacy, it would be advantageous to detect such effects prior to the onset of a cataract. Our MRI technique can detect precataractous changes in the lens water compartments (T2 values) months to years before opacities become manifest. The in vivo human and animal studies correlate well with in vitro NMR pulse relaxation data on such lenses. The MRI technique requires 2-4 minutes per eye and provides excellent pictures of the globe as well as T2 values. These data correlate well with our in vivo lens fluorescence technique thereby providing two parameters capable of evaluating potential drug induced changes in the lens well before the cataract becomes manifest. PMID- 2100163 TI - Ocular digitalis effects in normal subjects. AB - Several visual functions were examined before and during self-application of therapeutic doses of digitoxin. The ERG recordings showed a reduction of the critical flicker fusion frequency from 70 Hz to 35-40 Hz. Recovery of color vision after macular photostress was examined with Nagel's anomaloscope and Jaeger's tritanomaloscope. After digitoxin intake the matching range at the tritanomaloscope was enlarged. Following macular photostress the recovery time of both the Rayleigh and the Trendelenburg matches was significantly prolonged. The mesoptometer readings did not show any changes during the application of digitalis. This demonstrates that the process of neural adaptation is intact during digitoxin therapy. The error score in the Lanthony desaturated 15 panel test was slightly increased after digitalis application. The Farnsworth-Munsell 100-hue test showed a marked increase in the total error score. There were no changes in the standard panel D-15. The Ishihara pseudoisochromatic plates were read without mistakes after digitalis medication. The chromatic visual acuity for red-green and blue was examined by recording the maximum reading distance for the Velhagen pseudoisochromatic plates "65" (Jaeger's test) and "49". For both plates the reading distance was reduced by 50% during digitoxin therapy. Computerized perimetry by colored stimuli (Tubingen Automatic Perimeter by Aulhorn and Durst) did not reveal any definitive changes in sensitivity thresholds with therapeutic serum levels of digitalis. Spectral increment sensitivity for the isolated blue cone system (Wald-Marre approach) was not influenced by therapeutic doses of digitoxin. Topical digitoxin application (0.02 mg/10 ml) did not interfere with the pupillary light reflex (infrared pupillography) or with the accommodative amplitude or intraocular pressure. It did, however, result in toxic keratopathy with swelling of endothelial cells and edema of the corneal stroma and epithelium. All changes disappeared after withdrawal of digitalis. PMID- 2100164 TI - Toxicity of intraocular daunomycin. AB - Due to its antiproliferative properties, daunomycin is of potential use in the treatment of proliferative vitreoretinopathy and capsular fibrosis after cataract extraction. Previous biomicroscopic, electrophysiologic and histologic studies in the rabbit had shown that higher drug doses caused damage to all ocular structures after exposure to daunomycin. Based on the animal studies, we concluded that there is a small but usable therapeutic window for this drug. As electrophysiology and histology are not readily available for the examination of the human silicone-filled eye, we used clinical examination and fluorescein angiography as toxicity parameters. The comparison of the visual acuity and the central visual field showed that visual acuity is a reliable parameter of retinal and macular function after vitreoretinal surgery. Any specific toxicity attributable to daunomycin could not be observed in our patients. We conclude that the daunomycin perfusion (7.5 mg/l for 10 min.) is well tolerated by the human eye. PMID- 2100165 TI - Surface anesthetic effect and topical tolerance of one dose 0.25% bupranolol in eye-healthy people. AB - In a randomised, prospective, parallel, double-masked study we examine the surface anesthetic effect of Bupranolol 0.25% in an oily solution. Bupranolol 0.25% decreases the corneal sensitivity to 23 mg/S, with the maximum between the 6th and 15th minute after application. PMID- 2100166 TI - Use of a specular microscope with pachymeter in ocular tolerance studies of eye drops in the rabbit. Evaluation of ocular tolerance of benzalkonium chloride in aqueous solution 0.01% and 0.1%. AB - Eye drops, unlike cosmetics or chemicals, only cause minor irritations which often prove difficult to objectively observe and assess. A specular microscope with pachymeter is used to measure corneal thickness, and to examine and photograph corneal endothelium in ocular tolerance studies in the rabbit. Rabbits were instilled 5 times a day for 16 days with BKC aqueous solution, 0.01% or 0.1% and subjected after anaesthesia to 4 corneal inspections (before treatment, 7th and 14th days of treatment, 5th day after treatment). Only the 0.1% concentration provoked an increase in corneal thickness. Thickening progressed during the treatment period (5.3% on day 7, 26% on day 14) and strongly regressed 5 days after treatment stopped (3%). A slit lamp examination revealed very light or light corneal opacities, but the correlation between corneal thickening ratio and opacity was poor (r = 0.62). PMID- 2100167 TI - Permeability of the limiting cell layers of the cornea in vivo. AB - The permeability of the limiting cell layers of the cornea for solutions is of special interest with respect to the following points of view: 1) Protection against penetration of fluids from the tear film or aqueous into the stroma. 2) Nutrition of various corneal tissues from the tear film or from the aqueous humor. 3) Penetration of topically applied drugs into the anterior segment. 4) Side effects of drugs or surgery on the permeability of epithelial or endothelial layers. Fluoresceine sodium as a hydrophilic weak acid (MG 360) penetrates intercellulary through intact epithelium and endothelium. When topically applied the rise of fluoresceine concentration in the stroma depends on the permeability of the epithelium, whereas that in the aqueous may be controlled by the endothelial permeability. Small impairment of these cell layers leads already to increased permeabilities. This means that valuable information on the pathology of epithelial and endothelial layers may be obtained by quantitative clinical determination of the fluoresceine concentration by aid of sensitive fluorophotometers. PMID- 2100168 TI - Cytotoxicity of hydrogen peroxide to human corneal epithelium in vitro and its clinical implications. AB - We investigated the cytotoxicity of hydrogen peroxide by exposing primary confluent cultures of human corneal epithelium to a single dose of this agent at concentrations ranging from 30 ppm to 100 ppm in the tissue culture medium. Our criteria for cytotoxicity included alterations in cytokinesis and movement of the cells, changes in cell morphology, and mitotic index, and cell degeneration and death. At a concentration as low as 30 ppm, hydrogen peroxide caused rapid cell retraction as well as cessation of cytokinesis and mitotic activity; formation of membranous vesicles preceded cell death, which occurred by seven to eight hours after exposure. At a concentration of 50 ppm, normal cell activity ceased almost instantaneously; numerous surface vesicles formed by 1.5 hours of exposure, and the cells died within four to five hours. Higher concentrations (70 to 100 ppm) of hydrogen peroxide caused cell death within a few minutes. Because neutralization of hydrogen peroxide and patient compliance with the manufacturer's instructions are critical in the proper use of peroxide-based disinfection systems, users should be aware of possible short- and long-term iatrogenic toxicity of residual peroxide on the cornea. PMID- 2100170 TI - Particulate matter contamination in the corneal stroma of severe eye burns in humans. AB - Corneal buttons obtained from keratoplasty were examined by energy dispersive x ray analysis (EDXA) combined with scanning electron microscopy (SEM). This method enables to assay the mineral composition of minute parts of tissue samples identified in SEM images. Samples were cut from paraffin embedded corneae, deparaffinized in xylol, dried in aceton, critical-point desiccated, covered by evaporating with a thin layer of carbon and examined by SEM. In healthy human donor eyes, only some iron particles had been found. In the 22 patients samples high amounts of different particles were identified, materials from rubber stoppers, chromesteel, titanium pigments, talcum, barium and glass. Furthermore a lot of different metal particles containing varying amounts of Na, Mg, Al, Si, P, S, Cl, K, Ca, Fe, Cu, Cr, Zn, La and Ce were detected. Some particles may be caused by the initial trauma, others by therapy. Such contaminations might have supported leucocyte and fibrocyte invasion increasing the inflammatory reaction in the burnt cornea. PMID- 2100169 TI - Role of glutathione in the regulation of anterior chamber hydrogen peroxide. AB - Catalase inhibition leads to an increase in the t 1/2 for hydrogen peroxide loss from the anterior chamber and increased tissue damage. BCNU (1,3-bis-(2 chloroethyl)-l-nitrosourea) and BSO (buthionine sulfoxamine) were used to suppress glutathione reductase and glutathione synthesis, respectively. Intravitreal BSO (1 to 4 mg) reduced total glutathione levels of iris by 80%, and aqueous glutathione levels by 70%. BSO caused the t 1/2 for hydrogen peroxide disappearance from the anterior chamber to increase after 10 microliters of 10 mM peroxide was injected intracamerally but not after 25 or 50 mM peroxide injections. Catalase inhibition, however, had more influence at 50 mM than with 10 or 25 mM injections. The glutathione redox system is operative at low aqueous hydrogen peroxide concentrations and catalase is of greater importance at higher peroxide concentrations. PMID- 2100171 TI - Corneal silver deposits following Crede's prophylaxis an examination with electron dispersive x-ray analysis (EDX-analysis) and scanning electron microscope (SEM). AB - In a case of silver nitrate injury after Crede's prophylaxis, the cornea of a newborn presented yellow-brown, lime-like plaques on the nasal part of the right eye. A paracentral ulcerating stromal opacification undermined these appositions, when the patient was admitted to the eye-clinic at Aachen. In the material obtained by a lamellar keratectomy scanning electron microscopical examination was able to prove the existence of granules, previously described in light microscopy. These granules measured 100 to 300 nm in diameter. An earlier chemical analysis of necrotic material showed no silver specific reaction. By means of EDX-analysis these granules could be identified as silver-containing. Injuries by silver nitrate solutions used for Crede's prophylaxis are seldom but still reported. The mechanism of injury in this case of a child, born by sectio remains unknown. Neither the use of an unusual silver nitrate solution, that was taken from a disposable ampoule (Mova-Nitrat R) was reported, nor any corneal injury during sectio mentioned. Nevertheless the method of EDX-analysis and SEM proved the diagnosis of corneal silver deposits, so that the origin of the granullar opacification of the cornea could be determined. PMID- 2100172 TI - Beta-cyclodextrins as vehicles in eye-drop formulations: an evaluation of their effects on rabbit corneal epithelium. AB - Beta-cyclodextrins are cyclic molecules with a hydrophilic outer side and a central hydrophobic cavity. Through the inclusion of drug molecules into their cavities, i.e. the formation of inclusion complexes, cyclodextrins are able to modify the physical and chemical properties of these molecules. When used in pharmaceutical formulations, they can improve the aqueous solubility, stability, dissolution rate, bioavailability and/or local tolerance of certain drugs. To make an initial evaluation of the potential use of beta-cyclodextrins as vehicles in ophthalmic eye-drop formulations, we studied the effect of a single and of multiple applications of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) 12.5% and of dimethyl-beta-cyclodextrin (DM-beta-CD) 5 and 12.5% solutions on the corneal epithelium of albino and pigmented rabbits with slit lamp biomicroscopy (SLB) and scanning electron microscopy (SEM). We can conclude from this study that DM-beta CD at concentrations of 5 and 12.5% is not a suitable vehicle for ophthalmic formulations since it is toxic to the corneal epithelium and that HP-beta-CD at a concentration of 12.5% is well tolerated by the rabbit eye and is not toxic to the corneal epithelium when evaluated by SLB and SEM. PMID- 2100173 TI - In vitro toxicity of lomefloxacin in rabbit corneal epithelial cell cultures. AB - Lomefloxacin (NY-198) is a chemotherapic agent from the new 4-quinolone group, acting on DNA gyrase system. Lomefloxacin (LFLX), as some other new 4-quinolone compounds are antimicrobials of potential use for ophthalmic application. A first approach on the oculotoxicity of LFLX is the main purpose of this study. Four concentrations of LFLX (10, 30, 100 and 300 micrograms/ml) were tested on the first subculture of pigmented rabbit corneal epithelial cells. Cell number, protein contents, neutral red stain and wound healing were evaluated. The results showed that the lower concentrations (10 & 30 micrograms/ml) had no effect while the highest one had a remarkable cytotoxic effect. Pharmacokinetic data show that peak values achieved in the cornea and other ocular structures are lower than 40 micrograms/g (0.3% topical application) and, on another hand, MIC values range from less than or equal to 0.05 to 16 micrograms/ml. So, these "critical" concentrations have no cytotoxic effects according to our results. Then, it is concluded that Lomefloxacin could be a useful drug for topical ophthalmic development. PMID- 2100174 TI - Techniques of intraocular pressure determination. AB - A variety of indentation or applanation tonometers are available for the measurement of intraocular pressure in conscious or anesthetized animals. The Schiotz tonometer is a simple indentation tonometer, but unless used properly can give misleading values. Applanation tonometers include the air tonometer, pneumatonograph, and the Goldmann type (either slit-lamp or hand-held models). These flatten a small, fixed area of cornea and measure the resultant pressure. In anesthetized animals anterior chamber cannulation may be performed, although breakdown of the blood-aqueous barrier can ensue together with an alteration of intraocular pressure. Of importance is that all tonometers be calibrated for each species since scleral rigidity, ocular curvature, pressure/volume relationships, etc. all vary between species. PMID- 2100175 TI - The protein distribution of bovine, human and rabbit aqueous humour and the difference in composition before and after disruption of the blood/aqueous humour barrier. AB - The protein distribution of bovine, monkey, dog, human and rabbit aqueous humour (AH) was determined by capillary isotachophoresis (ITF). The main component was albumin, and components of lower concentrations were transferrin, IgA and IgG. The results of the analysis by ITP were confirmed by immunoelectrophoresis. The appearance of the ITP patterns of normal AH's from 5 species was almost identical, the same main components were present in the AH of each species. When the blood/AH barrier was disrupted, the protein composition of the AH was changed abruptly. ITP was the technique of choice to determine quantitative changes in protein composition of the AH's. In rabbit secondary AH, ITP showed high proportions of albumin and enhanced concentrations of transferrin. Examples were given of the difference between early and late aspiration in bovine and rabbit. The ITP was thus the method of choice to confirm whether the blood/aqueous humour barrier was intact or damaged by the influence of a drug, given to experimental animals. PMID- 2100176 TI - Application of an anterior eye segment analysis system in clinical cataract research. AB - Clinical application of a newly developed ANTERIOR EYE SEGMENT ANALYSIS SYSTEM was introduced. By this system, a Scheimpflug and a retroillumination image of the anterior eye segment are obtained through a CCD camera, separately. To overcome difficult problems experienced with previous types of lens documentation systems, several kinds of new mechanisms were built into this system. Slit and retroillumination images of some cases with cataracts and some examples of anterior eye segment analysis were described. PMID- 2100177 TI - Comparison of Scheimpflug-photography, specular microscopy and scanning electron microscopy to detect corneal changes in toxicity studies in rats. AB - With an increasing number of in-vivo methods to examine the eyes of laboratory animals, the rat has become an important animal model in experimental eye research. Specular microscopy is a clinical tool to examine the corneal endothelium in-vivo. To evaluate the versatility of this method for small animal eyes, we studied both corneal endothelial cell-count and corneal thickness in normal rats as well as those with diabetic, naphthalene and UV-B cataract. As a reference scanning electron microscopy (SEM) of the corneal endothelium was performed. For cell-counts the correlation coefficient between both methods was found to be sufficient. The comparison of corneal thickness measurement (SEM values) with specular microscopy and with Scheimpflugbiometry failed to show a satisfactory correlation. The study proves that specular microscopy is a useful tool to document changes also in the endothelium of the rat-cornea. PMID- 2100178 TI - Crystallin profiles of calf and bovine lens microsections, stained for free sulfhydryl groups and proteins. AB - Calf and bovine lenses of 0.98 and 8.40 years old were separated mechanically into lens equator and inner cylinder. The inner cylinder was cut into 10 to 11 sections by a microsectioning device. These sections were investigated on the protein profiles of water-soluble crystallins, stained for proteins by Coomassie Blue (CB). These crystallins were also specifically stained purple for free sulfhydryl groups (SH). It appeared that all crystallins that were stained blue for proteins were also stained purple for sulfhydryl groups. This means that all crystallins contain free sulfhydryl groups. Going from anterior and posterior cortex to the nucleus of the lens, there was an appreciable increase of the percent of gamma-crystallins, whereas especially in the older lenses a decrease of gamma-crystallins could be observed in the lens equator and the anterior and posterior cortices. A stainability factor F = %SH/%CB was calculated for all crystallins. HM-, alpha- and beta s-crystallins exhibit high values of factor F. For the bovine lens, factor F of HM-crystallin displayed a maximum in the nucleus, whereas this factor decreased for gamma-crystallins towards the nucleus. This microsectioning technique allows for determining age-related differences between the sections obtained. This may lead to a comprehensive understanding of age-related changes within one lens, including cataractous changes. PMID- 2100179 TI - Elemental distribution in frozen-hydrated rat lenses with galactose cataract. AB - The elemental distributions in frozen-hydrated rat lenses with galactose cataract were compared before and after the onset of the nuclear cataract to investigate the possible role of ion levels in the lens opacification due to the phase separation of the lens cytoplasm. The maps of the weight concentrations of the minor elements, S, Cl, K and Ca, on the basis of wet weight in the central plane of lens were obtained by X-ray analysis with the high energy ion microprobe at a resolution of 50 microns. Before the onset of the nuclear cataract, the distributions of Cl and K, were almost normal, except in the lens posterior periphery with high Cl and low K. In the lens with the nuclear opacity, sudden changes were observed. The Cl increased throughout the lens, and K decreased throughout the lens except at lens anterior thin layer. However, the totalized monovalent ion level changed only slightly. The Ca level increased throughout the lens after the onset of the nuclear cataract, suggesting a possible role of Ca in the nuclear opacification of galactose cataract of rats. The distributions of S were similar to the protein density distributions previously known both in the normal and in the cataractous lenses. PMID- 2100180 TI - Lipid analysis in bovine lens parts after in vitro incubation in the presence of an HMG-CoA-reductase inhibitor. AB - Normal bovine lenses and bovine lenses after incubation in TC 199 in the presence of a lipid lowering drug were divided into four parts: the equatorial ring, the nucleus, the anterior cortex and posterior cortex. The lipids were extracted according to Egge et al. (1). Total lipids were determined gravimetrically, the lipid fractions phospholipids (PL), cardiolipin (CL), free fatty acids (FFA) and cholesterol (CH) were separated by thin layer chromatography and determined quantitative by densitometry after charring with 10% sulfuric acid. There are differences in lipid distribution between the four lens compartments, but there are no differences between normal and drug treated lenses in total lipids and lipid fractions. This result could be explained in different ways: either during this incubation time of 24 hours at 37 degrees C there will be no effect on the lens epithelial cells or there is no de-novo synthesis of lipids, especially of cholesterol in the bovine lens epithelium which could be influenced by lipid lowering drugs like HMG-CoA reductase inhibitors. PMID- 2100181 TI - Investigations on the presence of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase, E.C.1.1.1.34) in lenses of various animal species. AB - The cholesterol requirements of the lens for the formation of plasma membranes are met by self-synthesis immediately after birth, this capacity, however, decreases considerably with increasing age, so that the deficit can only be met by exogenous supply. These findings are of great importance with respect to the qualitative assessment of extra-hepatical side effects of the substance class of HMG-CoA-reductase inhibitors on possible disturbances of lens transparency. In contrast to investigations of Mosley et al. (23) with rat and rabbit lenses, we did not find any activity of the HMG-CoA-reductase in our experiments with the lens cortex of calf, bovine, Beagle dog. The disturbances in lens transparency observed in chronical toxicity tests with high doses of HMG-CoA- reductase inhibitors might rather be due to the impairment of the exogenous cholesterol supply by a considerable decrease of the normal cholesterol level in the blood. The therapeutical treatment of pathologically increased blood cholesterol levels of patients should therefore not affect the transparency of human lenses. Relevant drug-safety-clinical studies confirm this experimentally substantiated supposition. PMID- 2100182 TI - No lens changes caused by simvastatin results from a prospective drug safety study. AB - 45 patients suffering from a primary hypercholesterolemia were treated with Simvastatin. Additionally to internal visits regular ophthalmologic examinations were performed. The main interest concerning the ophthalmologic examination was directed toward the documentation and measurement of lens opacities by means of Scheimpflug photography. Moreover, every 6 months a complete regular ophthalmologic examination was carried out. We present the results after a time period of 2 years. Relevant changes in clinical findings could not be found. In some patients the Scheimpflug measurement revealed an increase in light scattering. These findings, however, were within the limit of normal age related changes. PMID- 2100183 TI - Influence of some factors on the sutures of the lens. AB - A clinical study of the lens transparency conditions was made on 118 patients with regard for an applicable treatment, the use of hyperbaric oxygenation and a type of lesion. It showed, that sutures of the lens were wider in patients with uveitis and in diabetic patients as compared with the control-group patients who had no other pathologies. Glaucomatous patients had very narrow sutures. Initial opacifications of the lens were perceived in patients with uveitis and in diabetic patients as stars oriented along sutures beneath the posterior capsule in the area of the nucleus. Following hyperbaric oxygenation and equally the corticosteroid therapy, there was a decrease in the thickness of the sutures, and the degree of transparency of the lenticular nucleus changed as well mainly in the zone bordering on the posterior cortex strata. The study underlines the importance of examination of the condition of the lens sutures in determining the toxic impact produced by different factors on the lens. PMID- 2100184 TI - Screening for potential in vivo phototoxicity in the lens/retina. AB - The eye is particularly vulnerable to damage from the phototoxic side effects of drugs since it is constantly subjected to ambient light. Presented here are several screens that can be used to determine the potential of drugs to cause light damage to the eye. These include a simple screen that takes into account the optical properties of the eye and the absorption spectra of the various drugs. This can be used to omit various drugs as potential photooxidants in the eye. In addition a second, more detailed screen is presented. This can be used to determine a) the quantitative potential for a drug to cause photooxidative damage in the eye, b) the mechanism by which it occurs and c) the in vivo verification of phototoxicity. PMID- 2100185 TI - The ERG as a complementary diagnostic tool in ophthalmoscopy in albino rats. AB - Using light induced retinal damage in albino rats as a model, the time of occurrence of lesions was investigated by ophthalmoscopy, electroretinography and light microscopy. Changes in the electroretinogram correlated well with histopathological lesions in the first retinal neuron. In contrast, ophthalmoscopy revealed no evidence of retinal damage even at a time, when the animals were apparently blind. It is concluded that electroretinography is an appropriate experimental tool for detection of retinal damage at a very early stage in toxicological investigation. PMID- 2100187 TI - Multifocal serous chorioretinitis in beagle dogs. AB - In the years 1988 and 1989, routine ophthalmological examinations of dogs from the company-owned beagle colony revealed a clinically inapparent chorioretinitis in 7.4 and 10% of the animals, respectively, as it has previously been described by Weisse et al. (1981). The alterations were seen mainly in the non-tapetal fundus, and they appeared more frequently in both eyes than in just one eye. Infection tests as well as virologic, bacteriologic and histopathologic investigations were performed in order to clarify the origin. A direct evidence of virus particles from processed ocular material by electron microscopy was not possible. Tests for growth on MDCK cells were negative. In bacteriologic tests, a gram positive, filiform, branched microorganism was isolated. The histopathologic findings in the subacute stage were a focal atrophy of the first retinal neuron and a focal proliferation of glia cells. PMID- 2100186 TI - Nontoxic concentration of ceftazidime and flomoxef sodium for intravitreal use- evaluated by in-vitro ERG. AB - The effects of ceftazidime (CAZ) and flomoxef sodium (FMOX) on the in-vitro electroretinogram (ERG) of albino rabbits were studied. The a-wave, the b-wave and the oscillatory potential (OP) were unchanged by 0.3mM (0.19mg/ml) CAZ containing solution. The OP was suppressed by 0.5mM (0.32mg/ml) CAZ. The a-wave, the b-wave and the OP were unchanged by 0.5mM (0.26mg/ml) FMOX. The OP was suppressed and its peak latency was delayed by 2mM (0.52mg/ml) FMOX. The concentration of 0.3mM (0.19mg/ml) CAZ was higher than its minimum inhibitory concentration (MIC) against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Serratia marcescens and Propionibacterium acnes. The concentration of 0.5mM (0.26mg/ml) FMOX was higher than its MIC against Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens and Propionibacterium acnes. PMID- 2100188 TI - Electroretinographical changes due to antimicrobials. AB - We evaluated the retinal toxicity of antimicrobials (sulbenicillin, cefazolin, flomoxef, gentamicin, sisomicin, netilmicin, tobramycin, amikacin, vancomycin, ofloxacin, lomefloxacin, and miconazole) by the electroretinogram, before and after a single-shot intravitreal injection in rabbits. The clinical dosage for single-shot intravitreal injections which we recommend are 2 mg for sulbenicillin, 0.25 mg for cefazolin, 0.2 to 0.4 mg for flomoxef, 0.1 mg for gentamicin, 0.1 to 0.2 mg for netilmicin, 0.2 to 0.4 mg for amikacin, 0.2 mg for tobramycin, 1 mg for vancomycin, 0.2 mg for ofloxacin, 0.2 mg for lomefloxacin, and 0.05 mg for miconazole. PMID- 2100189 TI - Observations on the incidence and significance of linear irregularities in the course of major retinal blood vessels in the fundus of the rat. AB - The ophthalmoscopic examination of rats receiving drug administered by daily intravenous bolus injection for 6 months revealed an increase in the incidence and amplitude of linear irregularities in retinal blood vessels with a tendancy towards tortuosity which appeared to be related to treatment. Subsequent critical observation of groups of untreated rats, and rats dosed orally with a vasodilator suggest this phenomenum may be related to haemodynamic mechanisms; and that more attention should be given to the dose volume administered intravenously in this species to avoid the detection of such ocular artefacts. PMID- 2100190 TI - Age-related retinal changes--comparison between albino and pigmented rats. AB - To characterize aging as a factor responsible for structural changes the retinae of 47 Wistar-derived albino rats and 50 pigmented rats of the Norway and BDE (Han) strains between the ages of 1 and maximal 36 month were examined by light and electronmicroscopy and analysed for changes in cell densities. In all 3 rat strains there was an overall decline in nuclear densities of outer layer nuclei by 38 - 50% and inner layer nuclei by 27 - 33% between the ages of 1 and 27 months. Over the same age-range the ganglion cell loss was comparable to the decline in the inner nuclear layer. Neuronal cell death occurred at all ages and was more pronounced in albino rats. Moreover, in albino rats, cones were more resistant than rods to destruction by age and ambient light. Age-related ultrastructural changes in the retinal pigment epithelial cells (RPE) were in both pigmented strains: (1) a substantial accumulation of lipofuscin, (2) an apparent thickening of the basement membrane and (3) absent or greatly enlarged pleomorphic basal infoldings. In up to 27-month old BDE (Han) and 36-month old Norway rats besides mature stage IV-melanosomes also stage III-melanosomes can be observed. Characteristic of RPE-cells in old rats of these two strains were also compound granules and compound melanosomes. In peripheral RPE-cells of albino rats premelanosomes can be sporadically detected up to 31 months of age. Age related changes in retinal vessels were found in the superficial and deep capillary network. The only finding was a 2-3 fold increase in thickness of the capillary basement membrane. PMID- 2100191 TI - Borna disease virus-induced retinitis in Lewis rats--an immune-mediated retinopathy. AB - Borna disease virus (BDV) infection, naturally occurring in horses and sheep induces a mononuclear retinitis and meningoencephalitis in adult Lewis rats. In the pathogenesis a virus-specific cell mediated immune reaction presumably of delayed hypersensitivity type is operative. Corresponding to the encephalitic lesions a progressive retinitis with loss of the first and second retinal neuron develops. The inflammatory response is characterized by predominance of macrophages in the early phase of infection followed by distinct plasmacellular infiltration. Immunosuppressed and immuno-incompetent rats do not develop retinal lesions after intracerebral inoculation. Thus similar as in the brain probably virus specific immunopathological reactions play a crucial role in the pathogenesis of BDV-induced retinitis in Lewis rats. PMID- 2100192 TI - TGF-beta: problems and prospects. AB - TGF-beta research is proceeding at an exponential pace. Studies in this area have become increasingly relevant to many areas of cell regulation, continually providing new surprises and findings. One may confidently predict that TGF-beta will be one of the key molecules in future attempts to establish an integrated view of the processes whereby cells coordinate their own and mutual functions. We have seen only the beginning, and this minireview is only a glimpse. PMID- 2100193 TI - Affinity modulation of the alpha IIb beta 3 integrin (platelet GPIIb-IIIa) is an intrinsic property of the receptor. AB - To analyze the basis of affinity modulation of integrin function, we studied cloned stable Chinese hamster ovary cell lines expressing recombinant integrins of the beta 3 family (alpha IIb beta 3 and alpha v beta 3). Antigenic and peptide recognition specificities of the recombinant receptors resembled those of the native receptors found in platelets or endothelial cells. The alpha IIb beta 3 expressing cell line (A5) bound RGD peptides and immobilized fibrinogen (Fg) but not soluble fibrinogen or the activation-specific monoclonal anti-alpha IIb beta 3 (PAC1), indicating that it was in the affinity state found on resting platelets. Several platelet agonists failed to alter the affinity state of ("activate") recombinant alpha IIb beta 3. The binding of soluble Fg and PAC1, however, was stimulated in both platelets and A5 cells by addition of IgG papain digestion products (Fab) fragments of certain beta 3-specific monoclonal antibodies. These antibodies stimulated PAC1 binding to platelets fixed under conditions rendering them unresponsive to other agonists. Addition of these antibodies to detergent-solubilized alpha IIb beta 3 also stimulated specific Fg binding. These data demonstrate that certain anti-beta 3 antibodies activate alpha IIb beta 3 by acting directly on the receptor, possibly by altering its conformation. Furthermore, they indicate that the activation state of alpha IIb beta 3 is a property of the receptor itself rather than of the surrounding cell membrane microenvironment. PMID- 2100194 TI - Simultaneous analysis of cell Ca2+ and Ca2(+)-stimulated chloride conductance in colonic epithelial cells (HT-29). AB - We used perforated patch, whole-cell current recordings and video-based fluorescence ratio imaging to monitor the relation of plasma membrane ionic conductances to intracellular free Ca2+ within individual colonic epithelial cells (HT-29). The Ca2(+)-mediated agonist, neurotensin, activated K+ and Cl- conductances that showed different sensitivities to [Ca2+]i. The Cl- conductance was sensitive to increases or decreases in [Ca2+]i around the resting value of 76 +/- 32 (mean +/- SD) nM (n = 46), whereas activation of the K+ conductance required at least a 10-fold rise in [Ca2+]i. Neurotensin increased [Ca2+]i by stimulating a transient intracellular Ca2+ release, which was followed by a sustained rise in [Ca2+]i due to Ca2+ influx from the bath. The onset of the initial [Ca2+]i transient, monitored at a measurement window over the cell interior, lagged behind the rise in Cl- current during agonist stimulation. This lag was not present when the [Ca2+]i rise was due to Ca2+ entry from the bath, induced either by the agonist or by the Ca2+ ionophore ionomycin. The temporal differences in [Ca2+]i and Cl- current during the agonist-induced [Ca2+]i transient can be explained by a localized Ca2+ release from intracellular stores in the vicinity of the plasma membrane Cl- channel. Chloride currents recover toward basal values more rapidly than [Ca2+]i after the agonist-induced [Ca2+]i transient, and, during a sustained neurotensin-induced [Ca2+]i rise, Cl- currents inactivate. These findings suggest that an inhibitory pathway limits the increase in Cl- conductance that can be evoked by agonist. Because this Cl- current inhibition is not observed during a sustained [Ca2+]i rise induced by ionomycin, the inhibitory pathway may be mediated by another agonist-induced messenger, such as diacylglycerol. PMID- 2100195 TI - Stimulus-response coupling: the search for intracellular calcium mediator proteins. PMID- 2100196 TI - Domain deletion in the extracellular portion of the EGF-receptor reduces ligand binding and impairs cell surface expression. AB - Cultured NIH-3T3 cells were transfected with cDNA constructs encoding human epidermal growth factor-receptor (EGF-R)* and two deletion mutants in the extracellular portion of the receptor molecule. One mutant is devoid of 124 amino terminal amino acids, and the other lacks 76 residues. Mutant receptors were not delivered to the cell surface unless the transfected cells contained also endogenous EGF-Rs, suggesting that receptor interaction complements the mutation and allows surface display of mutant receptors. Immunoprecipitation experiments revealed an association between mutant and endogenous EGF-Rs when both proteins were expressed in the same cell. Hence, receptor-oligomers may exist in the plane of the membrane even in the absence of ligand binding, and oligomerization may play a role in normal trafficking of EGF-Rs to the cell surface. Mutant receptors retained partial ligand binding activity as 125I-labeled EGF was covalently cross linked to both mutant receptors, and EGF stimulated, albeit weakly, their protein tyrosine kinase activity. Both mutant EGF-Rs bind EGF with a 10-fold lower affinity than that of the solubilized wild type EGF-R. These results provide further evidence that the region flanked by the two cysteine-rich domains plays a crucial role in defining ligand-binding specificity of EGF-R. PMID- 2100197 TI - The in vitro biological effect of nerve growth factor is inhibited by synthetic peptides. AB - Nerve growth factor (NGF)1 is a neurotrophic polypeptide that acts via specific receptors to promote the survival and growth of neurons. To delineate the NGF domain(s) responsible for eliciting biological activity, we synthesized small peptides corresponding to three regions in NGF that are hydrophilic and highly conserved. Several peptides from mouse NGF region 26-40 inhibited the neurite promoting effect of NGF on sensory neurons in vitro. Inhibition was sequence specific and could be overcome by increasing the concentration of NGF. Moreover, peptide actions were specific for NGF-mediated events in that they failed to block the neurotrophic activity of ciliary neuronotrophic factor (CNTF) or phorbol 12-myristate 13-acetate (PMA). In spite of the inhibition of NGF activity, peptides did not affect the binding of radiolabeled NGF. These studies define one region of NGF that may be required for neurotrophic activity. PMID- 2100198 TI - Posttranscriptional changes in growth factor-inducible gene regulation caused by antiproliferative interferons. AB - Growth factors stimulate quiescent fibroblasts to progress through G0/G1, in part by inducing the expression of genes whose products are necessary or permissive for cell proliferation. Interferons, by contrast, inhibit progress through G0/G1 by mechanisms that are poorly understood. We show, in BALB/c murine 3T3 fibroblasts (A31 cells), that alpha/beta-interferon (IFN) had no effect the growth factor-dependent induction of several messenger ribonucleic acids (mRNAs), including those encoding ornithine decarboxylase (odc), fibronectin and the c-fos and c-myc protooncogenes. However, IFN caused an abnormal accumulation of fibronectin and c-myc mRNA on polysomes and markedly increased the stability of c myc mRNA. Moreover, despite high, induced levels of mRNA, IFN inhibited the serum stimulated rise in odc enzyme activity and the increased rate of fibronectin protein synthesis. By contrast, IFN had no effect on c-fos protein synthesis, nor did it affect the synthesis of most, but not all, proteins detectable by two dimensional gel electrophoresis. The data suggest IFN inhibits proliferation by suppressing the expression of a subset of growth factor-inducible genes through a selective, posttranscriptional mechanism. PMID- 2100199 TI - Effects of phosphorylation of the neurofilament L protein on filamentous structures. AB - Effects of phosphorylation of the neurofilament L protein (NF-L) on the reassembly system were studied by both sedimentation experiments and low-angle rotary shadowing. Bovine spinal cord NF-L was phosphorylated with 3-4 mol/mol protein by either the catalytic subunit of cAMP-dependent protein kinase or protein kinase C. Phosphorylated NF-L could not assemble into filaments. Phosphorylation by either cAMP-dependent protein kinase or protein kinase C inhibited the same step of the reassembly process. Phosphorylated NF-L remained as an 8-chain complex even in favorable conditions for reassembly. The extent of the effect of phosphorylation on the filamentous structure of NF-L was also investigated by using the catalytic subunit of cAMP-dependent protein kinase. The amount of unassembled NF-L increased linearly with increased phosphorylation in the sedimentation experiments. Structural observations indicated that 1 or 2 mol of phosphorylation is enough to inhibit reassembly and to induce disassembly, and the disassembly process was also observed. The filaments were shown to unravel with disassembly. Star-like clusters, which we reported as being the initial stage of reassembly, were also identified. PMID- 2100200 TI - Human colon carcinoma cells use multiple receptors to adhere to laminin: involvement of alpha 6 beta 4 and alpha 2 beta 1 integrins. AB - In this study, we used clone A, a human colon carcinoma cell line, to characterize those integrins that mediate colon carcinoma adhesion to laminin. Monoclonal antibodies specific for the human beta 1 subunit inhibited clone A adhesion to laminin. They also precipitated a complex of surface proteins that exhibited an electrophoretic behavior characteristic of alpha 2 beta 1 and alpha 3 beta 1. A monoclonal antibody specific for alpha 2 (PIH5) blocked clone A adhesion to laminin, as well as to collagen I. An alpha 3-specific antibody (P1B5) had no effect on clone A adhesion to laminin, even though it can block the adhesion of other cell types to laminin. Thus, the alpha 2 beta 1 integrin can function as both a laminin and collagen I receptor on clone A cells. Although these cells express alpha 3 beta 1, an established laminin receptor, they do not appear to use it to mediate laminin adhesion. In addition, the monoclonal antibody GoH3, which recognizes the alpha 6 integrin subunit, also inhibited carcinoma adhesion to laminin but not to fibronectin or collagen I. This antibody precipitated the alpha 6 subunit in association with the beta 4 subunit. There was no evidence of alpha 6 beta 1 association on these cells. In summary, the results obtained in this study indicate that multiple integrin alpha subunits, in association with two distinct beta subunits, are involved in colon carcinoma adhesion to laminin. Based on the behavior of alpha 3 beta 1 and alpha 2 beta 1, the results also suggest that cells can regulate the ability of a specific integrin to mediate adhesion. PMID- 2100201 TI - Comparison of Ca2+ mobilizing activities of cyclic ADP-ribose and inositol trisphosphate. AB - We have previously shown that a metabolite of NAD+ generated by an enzyme present in sea urchin eggs and mammalian tissues can mobilize intracellular Ca2+ in the eggs. Structural determination established it to be a cyclized ADP-ribose, and the name cyclic ADP-ribose (cADPR) has been proposed. In this study, Ca2+ mobilizations induced by cADPR and inositol trisphosphate (IP3) in sea urchin egg homogenates were monitored with Ca2+ indicators and Ca2(+)-specific electrodes. Both methods showed that cADPR can release Ca2+ from egg homogenates. Evidence indicated that it did not act as a nonspecific Ca2(+)-ionophore or as a blocker of the microsomal Ca2(+)-transport; instead, it was likely to be operating through a specific receptor system. This was supported by its half-maximal effective concentration of 18 nM, which was 7 times lower than that of IP3. The receptor for cADPR appeared to be different from that of IP3 because heparin, an inhibitor of IP3 binding, had no effect on the cADPR action. The Ca2+ releases induced by cADPR and IP3 were not additive and had an inverse relationship, indicating overlapping stores were mobilized. Microinjection of cADPR into intact eggs induced transient intracellular Ca2+ changes and activated the cortical reaction. The in vivo effectiveness of cADPR was directly comparable with IP3 and neither required external Ca2+. In addition, both were effective in activating the eggs to undergo multiple nuclear cycles and DNA synthesis. These results suggest that cADPR could function as a second messenger in sea urchin eggs. PMID- 2100202 TI - Signal transduction by steroid hormones: nuclear localization is differentially regulated in estrogen and glucocorticoid receptors. AB - The glucocorticoid receptor accumulates in nuclei only in the presence of bound hormone, whereas the estrogen receptor has been reported to be constitutively nuclear. To investigate this distinction, we compared the nuclear localization domains of the two receptors and the capacity of their respective hormone-binding regions to regulate nuclear localization activity. As with the glucocorticoid receptor, we showed that the human estrogen receptor contained a nuclear localization signal between the DNA-binding and hormone-binding regions (amino acids 256-303); however, in contrast to the glucocorticoid receptor, the estrogen receptor lacked a second nuclear localization domain within the hormone-binding region. Moreover, the hormone-binding domain of the unliganded estrogen receptor failed to regulate nuclear localization signals, although it efficiently regulated other receptor functions. We conclude that the two receptors employ a common mechanism for signal transduction involving a novel "inactivation" function, but that they differ in their control of nuclear localization. Thus, despite the strong relatedness of the estrogen and glucocorticoid receptors in structure and activity, certain differences in their properties could have important functional implications. PMID- 2100204 TI - Human transferrin receptor internalization is partially dependent upon an aromatic amino acid on the cytoplasmic domain. AB - The objective of this work is to identify the elements of the human transferrin receptor that are involved in receptor internalization, intracellular sorting, and recycling. We have found that an aromatic side chain at position 20 on the cytoplasmic portion of the human transferrin receptor is required for efficient internalization. The wild-type human transferrin receptor has a tyrosine at this position. Replacement of the Tyr-20 with an aromatic amino acid does not alter the rate constant of internalization, whereas substitution with the nonaromatic amino acids serine, leucine, or cysteine reduces the internalization rate constant approximately three-fold. These results are consistent with similar studies of other receptor systems that have also documented the requirement for a tyrosine in rapid internalization. The amino terminus of the transferrin receptor is cytoplasmic, with the tyrosine 41 amino acids from the membrane. These two features distinguish the transferrin receptor from the other membrane proteins for which the role of tyrosine in internalization has been examined, because these proteins have the opposite polarity with respect to the membrane and because the tyrosines are located closer to the membrane (within 25 amino acids). The externalization rate for the recycling of the transferrin receptor is not altered by any of these substitutions, demonstrating that the aromatic amino acid internalization signal is not required for the efficient exocytosis of internalized receptor. PMID- 2100203 TI - Protein kinase C acts downstream of calcium at entry into the first mitotic interphase of Xenopus laevis. AB - Transit into interphase of the first mitotic cell cycle in amphibian eggs is a process referred to as activation and is accompanied by an increase in intracellular free calcium [( Ca2+]i), which may be transduced into cytoplasmic events characteristic of interphase by protein kinase C (PKC). To investigate the respective roles of [Ca2+]i and PKC in Xenopus laevis egg activation, the calcium signal was blocked by microinjection of the calcium chelator BAPTA, or the activity of PKC was blocked by PKC inhibitors sphingosine or H7. Eggs were then challenged for activation by treatment with either calcium ionophore A23187 or the PKC activator PMA. BAPTA prevented cortical contraction, cortical granule exocytosis, and cleavage furrow formation in eggs challenged with A23187 but not with PMA. In contrast, sphingosine and H7 inhibited cortical granule exocytosis, cortical contraction, and cleavage furrow formation in eggs challenged with either A23187 or PMA. Measurement of egg [Ca2+]i with calcium-sensitive electrodes demonstrated that PMA treatment does not increase egg [Ca2+]i in BAPTA injected eggs. Further, PMA does not increase [Ca2+]i in eggs that have not been injected with BAPTA. These results show that PKC acts downstream of the [Ca2+]i increase to induce cytoplasmic events of the first Xenopus mitotic cell cycle. PMID- 2100205 TI - Development of a laboratory robotic system for automated bioanalytical methods- I. The determination of theophylline in human plasma: a comparison between the robotized and manual method. AB - The quality of bioanalytical methods is often determined by the quality of sample preparation. Using a robot for sample treatment may give better results than manual sample preparation, since the robot lacks human behaviour and incidental errors that are part of it. The use of a laboratory robot has the additional advantage of giving each sample the same analytical history, resulting in better reproducibility. An automated method has been developed for the analysis of drugs in plasma using a laboratory robot. Theophylline was used as a probe drug. Sample preparation was automated with a Zymate II robot, followed by separation and quantitation on an HPLC-system. The robotic method showed a good correlation with the manual method, while sample throughput was doubled. PMID- 2100206 TI - Physico-chemical characterization of a new salt of ibuprofen. AB - A new salt of ibuprofen was prepared by reaction with t-butylamine; its formation was confirmed by IR and 1H-NMR spectroscopy. The salt was characterized by thermoanalytical, X-ray powder diffraction and solubility studies. The salt was found to be 1.5 times more soluble in water than was ibuprofen, with an enthalpy of solution of -8.84 kcal mol-1. PMID- 2100207 TI - Automation of pharmaceutical dissolution testing by flow injection analysis. AB - The different types of instruments used for monitoring pharmaceutical dissolution testing are presented. Their features and the need for automation are critically discussed. The advantages of flow injection analysis in this respect are illustrated by a variety of examples clearly showing its adaptability to the different problems posed by other automatic and non-automatic alternatives. PMID- 2100209 TI - Mechanistic study and kinetic determination of vitamin C. AB - A simple specific method for the determination of vitamin C has been investigated by elucidating the reaction mechanism of its oxidation with cerium(IV) in sulphuric acid media. The reaction kinetics and rate measurements which form the basis of this method were determined by following the decrease of the intense yellow colour of cerium(IV) at 405 nm. The fixed-time and fixed-concentration methods were investigated. The former was found to be more precise and was consequently used for the determination. Advantages of this method over the B.P. and other methods are discussed. PMID- 2100208 TI - Quantitation of human chorionic gonadotrophin (hCG) by radioreceptor assay. AB - A sensitive radioreceptor assay was developed for pharmaceutical preparations of human chorionic gonadotrophin with the use of rat testicular membranes as receptor preparation and human 125I-chorionic gonadotrophin as tracer. The addition of unlabelled human chorionic gonadotrophin or luteinizing hormone inhibited the binding of 125I-chorionic gonadotrophin to the receptors in a concentration dependent way. Concentrations of human chorionic gonadotrophin between 30-300 mIU ml(-1) were normally used for a three-dose assay fulfilling pharmacopoeial statistical requirements for assay validity. The relative standard deviation for five assays was 7%. Estimates of potency of commercial preparations of human chorionic gonadotrophin obtained with the radioreceptor assay correlated well with corresponding estimates from in vivo assays. The proposed radioreceptor assay, however, provides a considerable saving in the number of animals required, requires less technical support, and is more precise than the in vivo method. PMID- 2100210 TI - Determination of enantiomeric purity of ephedrine and pseudoephedrine by high performance liquid chromatography with dual optical rotation/UV absorbance detection. AB - A reversed-phase high-performance liquid chromatography (HPLC) method with dual optical rotation/UV absorbance detection has been developed for the determination of enantiomeric purity of ephedrine hydrochloride and pseudoephedrine hydrochloride using an achiral column. The method gave a correlation coefficient of 0.9997 for the plot of log(optical rotation response) versus log (concentration) over the range of 0.06-10 mg ml(-1) of (+)-ephedrine hydrochloride (20 microliters injection). The limit of detection was 1.0 micrograms. Enantiomeric purity is shown to be most readily determined by measuring optical rotation, alpha, and absorbance, A, responses for standard and unknown samples, and using the equation (alpha/A)u/(alpha/A)s = (2xu - 1)/(2xs - 1), where x is the mole fraction of one of the enantiomers and subscripts s and u refer to standard and unknown, respectively. In blind trials using unknown mixtures of (+)- and (+/-)-ephedrine hydrochloride and a (+)-ephedrine hydrochloride standard, enantiomeric purities were determined to +/- 0.4% (95% confidence level) with five or six replicate 50 micrograms injections. The method has also been applied to the determination of the enantiomer mole fraction of (+) pseudoephedrine hydrochloride in a cough linctus, giving xu = 0.99 +/- 0.01 with seven replicate injections of 20-fold diluted linctus samples containing 7.5 micrograms of the chiral compound being assayed. Unlike conventional polarimetry, the method does not require chemically-pure samples and can be orders of magnitude more economical in material. PMID- 2100211 TI - LC determination of the diastereomers of 1-(beta-D-glucopyranosyl)phenobarbital in human urine. AB - The "product enantioselectivity" associated with the urinary excretion of the phenobarbital N-glucoside conjugates has not been determined previously. A liquid chromatography method using gradient elution was developed for quantifying both phenobarbital N-glucoside conjugates, phenobarbital, and p-hydroxyphenobarbital. Following a single oral dose of phenobarbital to male Caucasian and Oriental subjects, both phenobarbital N-glucoside conjugates were observed in the urine. In seven subjects, 3.3-10.6% of the phenobarbital dose was detected as a single phenobarbital N-glucoside (S configuration at the C-5 position of the barbiturate ring). The other phenobarbital N-glucoside diastereomer accounted for less than 1.5% of the phenobarbital dose. The urinary excretion of the major phenobarbital N-glucoside diastereomer paralleled the urinary excretion of phenobarbital and was comparable in both Caucasian and Oriental subjects. These results indicate a pronounced selectivity for the formation and/or urinary excretion of the phenobarbital N-glucosides. PMID- 2100212 TI - Potentiometric determination of iodipamide using an iodipamide ion-selective electrode. PMID- 2100213 TI - Potentiometric determination of diazepam with a diazepam ion-selective electrode. PMID- 2100214 TI - Sensitive membrane electrodes for the determination of vitamin B1 and vitamin B6. PMID- 2100215 TI - A review of techniques for the analysis of boron in the development of neutron capture therapy agents. AB - The resurgence of interest in neutron capture therapy, which uses boron-10 labelled compounds and neutron irradiation as a technique for the treatment of cancer, has been accompanied by the application of a new generation of techniques for the analysis and imaging of boron in biological matrices. In this review, a description is given of the requirements for boron neutron capture agents and the achievements to date of the analytical techniques. PMID- 2100216 TI - Adsorptive voltammetric investigation of the interaction of cisplatin with cystine and human serum albumin. AB - The interaction of the anti-cancer drug cisplatin with human serum albumin and cystine has been investigated using differential pulse adsorptive voltammetry. Based on an understanding of the voltammetric behaviour of these biological molecules, which rely on the presence of the disulphide groups within their molecular structure for their electroactivity, it has been postulated that binding of cisplatin to these molecules occurs at the disulphide bond. A fractional coefficient for the binding of cisplatin to human serum albumin at pH 7.4 was calculated to be 0.32. The reactivity of hydrolysis products of cisplatin was shown to be greater than that of the parent drug. PMID- 2100218 TI - Kinetic determination of sotalol by oxidation with sodium vanadate. AB - A kinetic method is described for the determination of sotalol. The method uses 0.033 M sodium vanadate to oxidize sotalol in 4 M sulphuric acid. The solution is heated at 90 degrees C and the absorbance is measured at 750 nm at a fixed time of 30 min. The concentration (c) of sotalol is calculated from the absorbance (A) by the equation: A = 0.04 + 0.0015625 c. PMID- 2100217 TI - Kinetic determination of vitamin B12 in pharmaceuticals by the continuous addition of reagent technique. AB - An automatic kinetic method for the determination of micro amounts of vitamin B12 in pharmaceutical samples based on the fast formation of a coloured complex between the cobalt contained by this vitamin and PAR [4-(2-pyridilazo)resorcinol] in a weakly alkaline medium and on the use of the continuous addition of reagent technique for the mixing of sample and reagent is reported. The reaction is monitored by measuring the changes in the absorbance at 510 nm characteristic of the complex formed. The linear range of the determination is 1.1-34.5 micrograms ml-1 and the relative standard deviation is 1.2%. The sample throughput is 75 h-1 (triplicate runs). The results obtained in analyses of pharmaceutical samples showed excellent correlation with nominal contents and the results of atomic absorption spectrophotometric analyses. PMID- 2100219 TI - Use of 1H NMR in the identification of a metabolite of a catecholic cephalosporin excreted in rat bile. PMID- 2100220 TI - Development of a laboratory robotic system for automated bioanalytical methods- II. A robot computer program for guarding totally automated bioanalytical methods. AB - The application of fully automated, unattended sample preparation performed by a laboratory robot for the analysis of drugs in biological samples requires the prevention of system failures which may arise in the on-line coupled chromatographic system or in other components of the robotic system. A computer program has been developed which can help to detect such problems. The control program for the robotic sample preparation contains a number of safety measures to intercept robotic or human errors. A routine is implemented, guarding for chromatographic malfunctions and errors in dispensing liquids by the robot. After detection of trouble, sample preparation is interrupted. PMID- 2100221 TI - Liquid chromatographic methods for the determination of albuterol (salbutamol), albuterol sulphate and related compounds in drug raw materials, tablets and inhalers. AB - Liquid chromatographic methods for the determination of albuterol (salbutamol), albuterol sulphate and related compounds in drug raw materials, tablets and inhalers are described. The methods resolve five known related compounds from the drug and, in the case of inhalers, several compounds not related to the drug. Two of these were identified as 2,6-di-t-butyl-4-methylphenol, a common antioxidant, and 2,2'-methylene bis(6-t-butyl-4-methylphenol). Related compounds are detectable at levels of about 0.03%. Eleven albuterol and 12 albuterol sulphate raw materials and eight tablet formulations were found to contain related compounds ranging from 0.03 to 0.54%, 0.09 to 0.50% and 0.32 to 0.95%, respectively. Non-drug compounds in three inhaler samples ranged from 4.6 to 12% of the drug delivered through the valve. Some of the non-drug compounds may be excipients. PMID- 2100222 TI - Determination of albuterol concentrations in human plasma using solid-phase extraction and high-performance liquid chromatography with fluorescence detection. AB - A fast, simple, and accurate method for determining albuterol concentrations in human plasma has been developed and validated for use in routine clinical analyses. This method involves a solid-phase extraction procedure using silica cartridges and normal-phase high-performance liquid chromatography with fluorescence detection. Regression analysis showed the method was linear over the standard curve range 1-16 ng ml-1. The percent recovery for albuterol and the internal standard, bamethane, at 5 ng ml-1 was found to be greater than 90%. The newly developed method has been applied in the analysis of plasma samples from patients and healthy volunteers. PMID- 2100223 TI - Determination of subtilisin proteolytic activity by flow-injection analysis with fluorescence detection. PMID- 2100224 TI - Deacetylated ketoconazole: a major ketoconazole metabolite isolated from mouse liver. PMID- 2100225 TI - An evaluation of the use of supercritical fluid chromatography with light scattering detection for the analysis of steroids. PMID- 2100226 TI - [Glossary of basic definitions for dental practice]. PMID- 2100228 TI - [Modified Widman flap--a standard method]. AB - The modified Widman flap offers such clinical advantages over root planing as root visualization. Treating periodontal pockets, which after preliminary treatment show a depth of 4 mm and more and remaining sulcus bleeding upon probing we obtained with this procedure a reduction of pocket depths and of gingival inflammation and gain of clinical attachment. The maintenance of these results as well as the further loss of attachment are directly related to the frequency of the maintenance recall appointments. The success of this procedure does not depend on the age of the patients. The healing following this procedure is normally achieved after 21 days and is by a long junctional epithelium, which may be seen as a stable treatment success. PMID- 2100227 TI - [Prophylaxis--duty of the patient or challenge for the dentist?]. AB - Effective preventive treatment requires detailed knowledge of the etiological factors which contributed to the respective disease. For this reason, the various concepts of infectious disease that were discussed at one time or another are presented here. Special attention is given to the nonspecific and the specific plaque hypotheses. Current preventive strategies are based, however, on the concept of "opportunistic infections", which is scientifically well-documented and has been described in much detail. The following three preventive strategies are feasible: (1) eliminating plaque regularly and completely; (2) eliminating plaque to the level of the individual patient's characteristic limits for the disease in question; and (3) effecting changes in the microbiological composition of the plaque in order to eliminate the more highly pathogenic organisms and possibly to replace them with less pathogenic organisms. PMID- 2100229 TI - [Osseointegrated implants ad modum Branemark in the oral rehabilitation of patients with advanced periodontal breakdown]. AB - Despite the achievements of modern periodontology, partially or completely edentulous mouths are unavoidable. The rehabilitation of such patients is a great challenge in oral health care. The state of the art of osseointegrated implants according to Branemark is described. Both full dentures and fixed partial dentures are discussed, with special emphasis on microbiological issues. The hypotheses are supported by substantial published evidence, and the problems discussed are further exemplified by a number of clinical case reports. The authors conclude that osseointegration according to Branemark is an effective long-term method for oral rehabilitation, and that the failure rate is low. One reservation that has to be made is that we are still waiting for the results of long-term studies on patients who are edentulous due to advanced adult periodontitis. This is the only way to evaluate in more detail the robustness of the tissues around the implantation site. PMID- 2100230 TI - [Resin bonding bridges--state of the art]. AB - Adhesive fixed partial denture (FPD) technology has gradually become viable in recent years, suitable for use in general dental practice. The most important prerequisites for success are patient selection and meticulous production techniques. Indications and limits of this technique are evaluated on the basis of the current state of the art. Initial preprosthetic treatment and clinical procedures are described. Research that has been done so far appears to demonstrate that adhesive FPDs are compatible with healthy periodontal tissues, even though some over-contouring of the adhesive tabs on the abutment teeth seems to be unavoidable. First clinical long-term studies have shown, however, that the failure rate of adhesive FPDs is higher than with conventional crown and bridge techniques. Porcelain-fused-to-metal FPDs on pure titanium frames and full ceramic FPDs are new developments in adhesive FPD technology which are not yet fit for use in dental practice. PMID- 2100231 TI - [Treatment of periodontal infrabony defects with alloplastic implantation materials]. AB - The implantation of alloplastic materials in infrabony defects is controversely discussed. Only calcium phosphate ceramics have been proven as implantation materials for clinical use. All of the materials not being inert they undergo biodegradation. The extent of biodegradation is most pronounced with tricalciumphosphate (TCP). It had been shown in clinical studies that reduction of probing depth and gain of probing attachment level increased with implantation when compared to surgery only. Formation of new attachment however, can only be verified by histological analysis. Block sections of human teeth demonstrated different results in terms of gain of attachment when porous hydroxyapatite (HA) was implanted. Histometric analysis of a study in dogs showed significant gain of attachment by implanting porous HA and TCP in infrabony defects. Using solid HA or a modified Widman flap healing occurred only by reparation forming a long junctional epithelium. In conclusion, it can be stated that regeneration of periodontal tissues may be achieved by means of implantation of porous HA and TCP. However, long term results are not available and the clinical parameters to obtain predictable results still have to be defined. PMID- 2100232 TI - [Clinical case report: adult periodontitis--a systematic approach to perioprosthetic management]. PMID- 2100233 TI - [Periodontology today]. AB - Periodontics overlaps regularly with the other dental disciplines and plays an important part in comprehensive dentistry. During the last decades a world-wide outgrowing research activity in basic science as well as in clinical research has contributed to a better understanding of the complexity of periodontal problems. The situation of periodontology in Germany must be improved. In order to obtain a better education in dental schools and consequently an optimal treatment of the patients, it is necessary to give to periodontology the same level of education as to other specialties in dentistry. Prophylaxis-oriented dentistry can only be established with the help of dental hygienists. PMID- 2100234 TI - [Periostar--a system for sharpening periodontal instruments]. PMID- 2100236 TI - [Employment of personnel as dental hygienists in a German dental office]. AB - The experience gained by the training of dental assistants using individual education programs shows that there is a need for similar training and education of dental hygienists. The presently existing education programs in this field are not related specifically to training of periodontal procedures and prophylaxis and are insufficient for the treatment of patients with periodontal diseases. This was also the conclusion of a committee for dental auxiliary personnel that was recently initiated by the German Society of Periodontology. PMID- 2100235 TI - [HIV-associated periodontal lesions]. AB - During HIV infection different lesions may occur in the area of the gingiva and/or the periodontium. An increased frequency and severity of periodontal diseases has been observed. Different forms of Candida albicans infection have been clinically characterized as pseudomembranous, erythematous (atrophic) or hyperplastic form or as papillary variant. While infection with Candida albicans may occur frequently in other areas of the oral mucosa, candidiasis of the gingiva seems to be quite rare. Due to the underlying immunodeficiency, HIV infected patients are prone to infection with and/or reactivation of different viruses, which may cause oral lesions as well. Recurrent progressive ulcerations may occur due to herpes simplex virus 1/2, while ulcerations with a punched-out appearance may result from disseminated CMV infection. Oral Kaposi's sarcoma may clinically present as bluish or red spots, which may increase into exophytic tumors during the progress of the disease. PMID- 2100237 TI - [Root surface instrumentation]. AB - The present status of root surface debridement is reviewed. Recently it was shown that the influence of root surface roughness and endotoxin-contaminated cementum was overestimated. The method of instrumentation (i.e., hand instrument, sonic or ultrasonic scaler) does not influence wound healing after periodontal surgery. The operator's technique is of utmost importance. PMID- 2100238 TI - [Fixed restorations of a dentition with reduced periodontal support in partially edentulous patients]. AB - Placing restorations in patients who have a limited number of teeth and reduced periodontal support is no longer controversial, given careful selection of patients, preprosthetic periodontal treatment, and a thorough maintenance program. In this paper, attention is drawn to general prosthetic planning, including the use of long-span bridges. Because of increased tooth mobility, cross-arch stabilization of the bridges with interlocks or with postsolder connections is advocated. The framework should be rigid enough to avoid deflection of the bridges. Preparation of the vital and nonvital abutment teeth needs much attention. To avoid using a removable prosthesis, a cantilever bridge can be used, but it makes the construction more prone to fracture. A number of periodontal-prosthetic patients demonstrate a "posterior collapsed bite." Rehabilitation requires the restoration at a "new" vertical dimension of occlusion. This can be done, without functional hazards, in a one-step clinical procedure. A long functional adaptation period is unnecessary. The treatment outcome of furcations is not always predictable. Therefore, hemisection or amputation are often the treatments of choice. On these hemisected roots, bridges can be made and successfully maintained. Finally, it should be stressed that not all teeth have to be replaced: a premolar, shortened-arch occlusion is often sufficient for adequate function. PMID- 2100239 TI - [Clinical aspects of gingival hyperplasia]. AB - This paper demonstrates the clinical variety of gingival enlargement. An increase of the number of individuals who suffer from local or general enlargement caused by microbial gingival inflammation or different drugs can be demonstrated. All imbalances of leukopoesis or homeostasis require particular diagnostic attention by dentists, because early diagnosis is decisive for patient prognosis. PMID- 2100241 TI - [Interdental brush--comparison of several systems]. PMID- 2100240 TI - [Clinical case report: coverage of a gingival recession with a free gingival graft]. AB - A clinical case is presented where a 100% root coverage is performed with a free gingival graft in a one step method. The surgery technique is described in detail. PMID- 2100242 TI - [Glossary of basic definitions for dental practice]. PMID- 2100243 TI - [Maintenance and sterilization of rotary dental instruments]. PMID- 2100244 TI - Synthesis and biological properties of A-71497: a prodrug of tosufloxacin. AB - Tosufloxacin (5, A-61827 tosylate or T-3262) is currently under product development by both Abbott Laboratories and Toyama Chemical Co. Its registration as antibacterial agent has been approved in Japan. It has been found to be extremely effective in treating several bacterial infections. However, due to its inherent low water solubility, the development of an intravenous formulation will be extremely difficult and may preclude its parenteral use. In search of a more water-soluble analog of tosufloxacin for parenteral use, the 3-formyl derivative of tosulfoxacin, A-71497 (13), was synthesized for evaluation. It was found to produce high plasma levels of tosufloxacin upon both oral and subcutaneous administration to mice. High plasma levels of tosufloxacin were also obtained when 13 was administered both orally and intravenously to dogs. It possesses increased water solubility and makes the development of intravenous formulation possible. The chemical synthesis as well as biological properties of A-71497 (13) are described. PMID- 2100245 TI - Antimicrobial activity of E-4441, a representative azetidine quinolone. AB - E-4441 is a third-generation difluoroquinolone characterized by the presence in position 7 of an azetidine ring, disubstituted in position 3 by amine and methyl groups. E-4322 is another difluoroquinolone which differs from the former in having a 3-acetidinol substitution in position 7. E-4441 shows satisfactory levels of activity, both in vitro and in vivo, its activity against G(+) aerobic bacteria and anaerobic bacteria being generally notable. PMID- 2100246 TI - Ramoplanin: a review of its discovery and its chemistry. AB - Ramoplanin is a novel antibacterial agent with characteristics that make it suitable for development as a topical treatment for acne, infected wounds, and for treatment of antibiotic-associated diarrhoea. In this paper, the authors will review the discovery process and the descriptive chemistry of this novel molecular entity. PMID- 2100247 TI - In vitro activity of ramoplanin on staphylococci. AB - Approximately 1000 strains of staphylococci isolated from the skin of patients before and after coronary artery by-pass surgery were speciated using the API Staph system, and tested for susceptibility to ramoplanin and teicoplanin. In addition flucloxacillin MICs were available for 750 strains. MICs were performed by incorporating dilutions of antibiotics in 'Isosensitest' Agar (Oxoid) and applying approx 10(4) cells by a multi-point inoculator. The strains tested (numbers in brackets) included: Staph. epidermidis (352), Staph. haemolyticus (133), Staph. simulans (104), Staph aureus (69), Staph. hominis (54), Staph. warneri (39), Staph. capitis (23), Staph. saprophyticus (12), Staph. cohnii (6) and Staph. sciuri (2). The overall MICs were: ramoplanin MIC 50%: 0.5 mg/l, MIC 90%: 1 mg/l; teicoplanin MIC 50%: 2 mg/l, MIC 90%: 8 mg/l. Ramoplanin MICs of greater than 2 mg/l were only found for 17 strains from eleven patients which included: Staph. simulans (6), Staph. haemolyticus (4) and Staph. epidermidis (2). The maximum MIC however was only 8 mgl, so no strains were ramoplanin resistant. There was no relationship between ramoplanin and flucloxacillin MICs; but despite their differing modes of action, the strains with higher ramoplanin MICs also had higher teicoplanin MICs. PMID- 2100248 TI - Pharmacology of cefminox, a new bactericidal cephamycin. AB - Cefminox is a new cephamycin antibiotic possessing a D-amino acid moiety derived from D-cysteine at the C-7B side chain. Cefminox is active against a wide range of bacteria, especially Gram-negative and anaerobic bacteria. Cefminox shows excellent in vivo efficacy (ED50) which is higher than would be expected from its in vitro activity (MIC). Moreover, cefminox possesses more potent activity in suppression of bacterial regrowth than other cephems. These phenomena are surmised to be caused by strong bactericidal activity which is attributed to a dual action mechanism. PMID- 2100249 TI - In vivo activity of sertaconazole in experimental candidiasis in the mouse. AB - The antifungal activity of sertaconazole (SZ), 1-(2-[(7-chlorobenzo[b]thien-3 yl)methoxyl]- 2-(2,4-dichlorophenyl)ethyl)-1H-imidazole, has been assessed in vivo in comparison with miconazole (MZ) in a murine vaginal candidiasis model. Mice (eight per group) were maintained in oestrus by subcutaneous injection of oestradiol benzoate (25 mg/kg) 5 days before and 2 days after inoculation intravaginally with 5 x 10(4) blastospores of C. albicans (strain No. 17) in 0.05 ml. Animals were treated with 0.03 ml of the appropriate 2% cream formulation 1 h after infection (single dose regimen) or on days 3, 4 and 5 post-infection (three dose regimen). The efficacy was measured in each test group by Sabouraud agar plate count of vaginal specimens and expressed as % reduction in the number of yeast cells with regard to the control group (infected and untreated). The two treatments indicated a significant reduction (according to the non-parametric method of Mann-Whitney) (p greater than 0.05) for both SZ (97.9% and 93.6%) and MZ (77.5% and 76.9%) groups. When the values from SZ and MZ were compared, SZ proved more active than MZ in the single dose regimen. PMID- 2100250 TI - The pharmacology of the anorexic effect of phenylpropanolamine. AB - Phenylpropanolamine (PPA), the racemic mixture of d- and I-norephedrine, suppresses appetite in a variety of species and reduces body-fat content and weight. Explanations of the anorexic action of PPA have often started with the view that PPA is but a minimally potent variant of the amphetamine molecule. Yet studies conducted in the last 5 years reveal a number of important differences as to the site of action and neurochemical mechanism of action of amphetamine and PPA. The anorexic capacity of amphetamine is mediated by dopaminergic and beta adrenergic activity within the perifornical hypothalamus (PFH). Direct injections of amphetamine within the PFH suppress feeding whereas PPA injections do not. Destruction of brain tissue that negates the anorexic action of amphetamine is without effect on PPA anorexia. Pharmacological blockade of dopamine receptors, using haloperidol, reduces amphetamine anorexia but is without effect on PPA anorexia. Yet, direct injections of PPA and amphetamine into the paraventricular hypothalamus suppress feeding. With regard to non-feeding behaviour, amphetamine markedly enhances locomotion and induces euphoria whereas PPA does not. These results strengthen the argument that PPA is not simply a variant of the amphetamine molecule but is an anorectic of its own class without the marked side effects that compromise the anorexic capacity of amphetamine. PMID- 2100251 TI - Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. AB - We consider some of the problems involved in current discussions on stem cells in adult mammalian tissues. The present concepts involve a number of pitfalls, weaknesses and logical, semantic and classification problems. This indicates the necessity for new and well-defined concepts that are amenable to experimental analysis. One of the major difficulties in considering stem cells is that they are defined in terms of their functional capabilities which can only be assessed by testing the abilities of the cells, which itself may alter their characteristics during the assay procedure: a situation similar to the uncertainty principle in physics. The terms that describe stem cell functions are often not well defined and are used loosely, which can lead to confusion. If such context-dependent interactions exist between the manipulation and measurement process and the challenged stem cells, the question of, for example, the number of stem cells, in a tissue has to be posed in a new way. Rather than obtaining a single number one might end up with various different numbers under different circumstances, all being complementary. This might suggest that stemness is not a property but a spectrum of capabilities from which to choose. This concept might facilitate a reconciliation between the different and sometimes opposing experimental results. Given certain experimental evidence, we have attempted to provide a novel concept to describe structured cell populations in tissues involving stem cells, transit cells and mature cells. It is based on the primary assumption that the proliferation and differentiation/maturation processes are in principle independent entities in the sense that each may proceed without necessarily affecting the other. Stem cells may divide without maturation while cells approaching functional competence may mature but do not divide. In contrast, transit cells divide and mature showing intermediate properties between stem cells and mature functional cells. The need to describe this transition process and the variable coupling between proliferation and maturation leads us to formulate a spiral model of cell and tissue organisation. This concept is illustrated for the intestinal epithelium. It is concluded that the small intestinal crypts contain 4-16 actual stem cells in steady state but up to 30-40 potential stem cells (clonogenic cells) which may take over stem cell properties following perturbations. This implies that transit cells can under certain circumstances behave like actual stem cells while they undergo maturation under other conditions. There is also evidence that the proliferation and differentiation/maturation processes are subject to controls that ultimately lead to a change in the spiral trajectories.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2100252 TI - Gradients of homeoproteins in developing feather buds. AB - Homeoproteins are functionally involved in pattern formation. Recently, homeoproteins have been shown to be distributed in a graded fashion in developing limb buds. Here we examine the expression of homeoproteins in chicken feather development by immunocytochemical localization. We find that XlHbox 1 antigen is present in cell nuclei and is distributed in a gradient in the mesoderm of developing feather buds, with strongest expression in the anterior-proximal region. The gradient is most obvious in feather buds from the mid-trunk level. Feather buds from the scapular level express very high levels of XlHbox 1 and feather buds from the caudal region express no XlHbox 1, suggesting that a broad gradient along the body axis is superimposed on a smaller gradient within each individual feather bud. Feather ectoderm also expresses XlHbox 1 antigen but without an obvious graded pattern. Another homeoprotein, Hox 5.2, is also expressed in developing feather buds in a graded way, and its distribution pattern is partially complementary to that of XlHbox 1. These observations suggest that homeoproteins may be involved in setting up the anteroposterior polarity of cell fields at different levels, first for the body axis, then for the limb axis and finally for the feather axis. PMID- 2100253 TI - A cytoplasmic determinant for dorsal axis formation in an early embryo of Xenopus laevis. AB - In Xenopus laevis, dorsal cells that arise at the future dorsal side of an early cleaving embryo have already acquired the ability to cause axis formation. Since the distribution of cytoplasmic components is markedly heterogeneous in an egg and embryo, it has been supposed that the dorsal cells are endowed with the activity to form axial structures by inheriting a unique cytoplasmic component or components localized in the dorsal region of an egg or embryo. However, there has been no direct evidence for this. To examine the activity of the cytoplasm of dorsal cells, we injected cytoplasm (dorsal cytoplasm) from dorsal vegetal cells of a Xenopus 16-cell embryo into ventral vegetal cells of a simultaneous recipient. The cytoplasm caused secondary axis formation in 42% of recipients. Histological examination revealed that well-developed secondary axes included notochord, as well as a neural tube and somites. However, injection of cytoplasm of ventral vegetal cells never caused secondary axis and most recipients became normal tailbud embryos. Furthermore, about two-thirds of ventral isolated halves injected with dorsal cytoplasm formed axial structures. These results show that dorsal, but not ventral, cytoplasm contains the component or components responsible for axis formation. This can be the first step towards identifying the molecular basis of dorsal axis formation. PMID- 2100254 TI - Insect epidermis: polarity patterns after grafting result from divergent cell adhesions between host and graft tissue. AB - Insect epidermal cells display planar polarity (i.e. polarity in the plane of the cell sheet) by secreting oriented cuticular denticles and bristles before each moult. We investigate how cell polarities in an abdominal segment are uniformly oriented towards the posterior of the animal. Recently we have shown for the cotton bug Dysdercus that, in 180 degrees-rotated grafts pretreated with colchicine, graft cells tend to adopt the orientation prevailing in surrounding host cells via an intermediate stage with outward oriented denticles (Nubler-Jung and Grau, 1987). Here we show that, in untreated grafts that were transposed along the anteroposterior segment axis, the denticles also always tend to point outwards. This independence of the polarity pattern from the direction of transposition is compatible neither with a gradient model for polarity control, nor with the assumption that epidermal cells orient according to the local sequence of distinctly differentiated cells. Instead we found that outward orientation of graft denticles correlates with an elongation of epidermal cells along a host-graft border with divergent cell adhesiveness. We therefore propose that outward orientation in a graft results from a combination of two factors: epidermal cells stretch along an interface with divergent cell adhesiveness, and they form a denticle perpendicular to their long axis. By analogy, the normal anteroposterior orientation of denticles in a segment may result because epidermal cells tend to elongate parallel to the segment boundary and to form denticles perpendicular to this mediolateral cell elongation, i.e. along the anteroposterior segment axis. PMID- 2100255 TI - Retinoic acid modulation of the early development of the inner ear is associated with the control of c-fos expression. AB - The effects of retinoic acid (RA) on the early development of the inner ear were studied in vitro using isolated chick embryo vesicles. Low concentrations of RA (1-50 nM) inhibited vesicular growth in stage 18 otic vesicles that were made quiescent and then reactivated by either serum or bombesin. Growth inhibition was concentration-dependent and was paralleled by a reduction in the rate of DNA synthesis as measured by [3H]thymidine incorporation. Half-inhibition occurred between 1 and 10 nM RA, and the full effect at 20 nM. Retinoic acid, in the presence of serum, induced the precocious differentiation of (1) secretory epithelium, the tegmentum vasculosum and endolymphatic sac and (2) early sensory and supporting epithelia. These structures were positioned in their corresponding normal presumptive areas. The overall direction of growth was reversed by RA and the ratio of the internal to the external vesicular surface area increased with RA concentration. The expression of the nuclear proto-oncogene c-fos in the developing otic vesicle was transient and stage-dependent. High levels of c-fos mRNA were positively correlated with cell proliferation. Incubation of growth arrested otic vesicles with bombesin plus insulin at concentrations that induced cell proliferation produced a strong induction of c-fos. This mitogen-induced expression was suppressed by 25 nM RA. The results suggest (1) a role for retinoic acid in controlling the early development of the inner ear and (2) that this control is effected through the regulation of the proto-oncogene c-fos. PMID- 2100256 TI - Organotypic arrangement of mouse embryonic lung cells on a basement membrane extract: involvement of laminin. AB - The behavior of embryonic murine lung cells on a basement membrane extract (Matrigel) was investigated. Single cell suspensions generated by trypsinization of lungs removed from day 12 embryos were plated on Matrigel and cultured for up to one week. The basement membrane extract was used as a gel, and as a wet or dried film. In all of these instances, organotypic arrangement of the embryonic lung cells was observed. This process consisted of cell aggregation, sorting, polarization and formation of a tridimensional organization resembling embryonic lung. The maximal degree of organotypic development was obtained by using a thick gel; minimal reorganization was observed using a dried film. A rabbit polyclonal serum to laminin inhibited organotypic pattern formation while normal rabbit serum did not. Culture of lung cells on laminin gels promoted epithelial cyst formation but poor mesenchymal organization. By studying the behavior of epithelial and/or mesenchymal enriched cell populations on Matrigel, it was concluded that organotypic pattern formation on Matrigel required the presence of both cell populations. Cultivation of dissociated lung cells on a gel consisting of a mixture of collagens type I and III (Vitrogen-100) produced only cell aggregation. Cultivation of lung cells on a thin film of Vitrogen-100 or on uncoated tissue culture plastic produced monolayers of mesenchymal cells alone. Cultivation of lung cells in suspension also failed to induce organotypic arrangement even at maximal cell densities. The present study strongly supports a role for the basement membrane in the organotypic rearrangement of embryonic lung cells and subsequent in vitro cyst formation and budding of the reestablished epithelium. This, in turn, reinforces the concept of the basement membrane as a major regulator of organogenesis. PMID- 2100257 TI - Postimplantation development of tetraploid mouse embryos produced by electrofusion. AB - Despite the fact that a variety of experimental techniques have been devised over the years to induce tetraploid mammalian embryonic development, success rates to date have been limited. Apart from the early study by Snow, who obtained development to term of a limited number of cytochalasin B-induced tetraploid mouse embryos, no other researchers have achieved development of tetraploid embryos beyond the early postimplantation period. We now report advanced postimplantation development of tetraploid mouse embryos following electrofusion of blastomeres at the 2-cell stage, and subsequent transfer of these 1-cell 'fused' embryos to appropriate recipients. Cytogenetic analysis of the extraembryonic membranes of all of the postimplantation embryos encountered in the present study has provided an unequivocal means of confirming their tetraploid chromosome constitution. A preliminary morphological and histological analysis of the tetraploid embryos obtained by this technique has revealed that characteristic craniofacial abnormalities particularly involving the forebrain and eyes were consistently observed, and these features were often associated with abnormalities of the vertebral axis and heart. The most advanced viable embryo in this series was recovered on the 15th day of gestation, and its morphological features suggest that it was developmentally equivalent to a normal embryo of about 13.5-14 days p.c. PMID- 2100258 TI - Identification of vimentin and novel vimentin-related proteins in Xenopus oocytes and early embryos. AB - We have made antibodies against fusion proteins of Xenopus vimentin. We show for the first time the distribution of vimentin in larval stages, where it is found in cells of mesenchymal origin, and in radial glial cells. In sections of Xenopus oocytes and early embryos, immunocytochemistry reveals the presence of an extensive cytoplasmic network, distributed in an animal-vegetal gradient. Germ plasm stains particularly strongly. The form of the IF proteins in this network is unusual. In immunoblot experiments the anti-vimentin antibodies detect a number of distinct proteins. We have identified those that are the products of the two known vimentin genes, by injection of synthetic mRNA transcribed from cloned vimentin cDNAs into oocytes, followed by two-dimensional Western blotting. This has demonstrated unambiguously that one Xenopus vimentin, Vim1, is present in oocytes and early embryos. However, two other immunoreactive proteins detected in Triton extracts of oocytes and early embryos are not the products of Vim1, since depletion of vimentin mRNA by antisense oligonucleotide injection has no effect on the synthesis of these proteins. These results suggest that novel IF like proteins are expressed in Xenopus oocytes and early embryos. PMID- 2100259 TI - The distribution of plasmodesmata and its relationship to morphogenesis in fern gametophytes. AB - Fern (Onoclea sensibilis) gametophytes when grown in the dark form a linear file of cells (one-dimensional) called a protonema. In the light two-dimensional growth occurs which results in a heart-shaped prothallus one cell thick. The objective of this paper is to relate the most common pattern of cell division observed in developing gametophytes to the formation of the plasmodesmatal network. Since the prothalli are only two dimensional, we can easily determine from thin sections the total number and the density (number per unit surface area) of plasmodesmata at each developmental stage. As the prothallus grows the number of plasmodesmata increases 50-fold in the apical or meristematic cell. This number eventually reaches a plateau even though the density continues to increase with each new cell division. What is particularly striking is that both the number and density of plasmodesmata between adjacent cells is precisely determined. Furthermore, the pattern of plasmodesmata distribution is predictable so that (1) we can identify the apical meristematic cells by their plasmodesmata number, or density, as well as by their size, shape and location, (2) we can predict, again from plasmodesmata number, the location of a future wall of the apical cell prior to its actual formation, (3) we can show that the density of plasmodesmata in the triangular apical cell of the prothallus (14 plasmodesmata microns-2) is comparable to those reported for secretory glands which are known to have high rates of plasmodesmatal transport and (4) we can show that once the plasmodesmata have been formed during division, no subsequent change in the number of plasmodesmata occurs following cell plate formation. PMID- 2100260 TI - Decoding positional information: regulation of the pair-rule gene hairy. AB - In the series of local gene activations that occur during early Drosophila development, the striped expression patterns of the pair-rule genes provide the first indication of segmental periodicity. The experiments that we report here address the question of how these patterns arise, by studying the regulation of one of these genes, hairy. We show that each of the seven stripes of hairy expression is controlled by a distinct subset of cis-acting regulatory elements, some mediating transcriptional activation and others transcriptional repression. In general, elements necessary and sufficient for triggering a particular stripe response are clustered on the DNA and appear to overlap or be interspersed with elements involved in at least one other stripe response. Our results extend previous findings suggesting that periodic hairy expression arises by a decoding process in which each stripe is triggered by particular combinations or concentrations of regulatory factors. These regulatory factors are likely to include the products of the gap class of segmentation genes that are required for activating or positioning particular subsets of hairy stripes and are expressed with overlapping distributions during early embryogenesis. PMID- 2100261 TI - An in situ assessment of the routes and extents of colonisation of the mouse embryo by embryonic stem cells and their descendants. AB - An embryonic stem (ES) cell line stably expressing lacZ under the control of an endogenous promoter has been isolated and used as a marker to follow the fate of ES cells injected into blastocysts and morulae, before midgestation. The results show a multisite pattern of blastocyst colonization by ES cells deposited into the blastocoel cavity and a low degree of mingling between ES cells and ICM cells. Furthermore, analysis of dispersal of ES cell descendants in postimplantation chimaeric embryos showed that colonization can be highly variable from one region of the embryo to another. In contrast, a high and reproducible degree of chimaerism was obtained when the ES cells were injected at the morula stage prior to ICM formation. PMID- 2100262 TI - Nucleolar distribution of proteins B23 and nucleolin in mouse preimplantation embryos as visualized by immunoelectron microscopy. AB - The ultrastructural distribution of proteins B23 and nucleolin in the nucleolus of mouse embryos from the zygote to the early blastocyst has been analyzed by means of specific antibodies and immunocytochemistry using colloidal gold complexes as markers. In parallel, silver staining of nucleoli was carried out on ultrathin sections. Our results show that the compact prenucleolar bodies at 1- and 2-cell stage as well as the compact residual fibrillar masses observed up to the morula stage, are labelled with the two antibodies. These masses, however, are not stained with silver up to the 4-cell stage. In well-developed nucleoli, the two antibodies co-localize in the dense fibrillar component (DFC) and the granular component (GC) while fibrillar centers (FCs) are devoid of label. On the contrary, silver staining occurs in the FCs and DFC but not in the GC. Our observations suggest that there is no direct relationship between the occurrence of silver staining and the distribution of protein B23 or nucleolin. Moreover, neither the localization of the two above proteins nor silver staining are unequivocally related to the nucleolar activity. PMID- 2100263 TI - Developmental loss of laminin from the interstitial extracellular matrix correlates with decreased laminin gene expression. AB - The expression of the polypeptide subunits of the glycoprotein laminin in developing mouse tissues was analysed by immunoblots and Northern blots, and by immunohistochemistry at the ultrastructural level. In the neonate, almost all the laminin of the sciatic nerve was freely extractable and was located mainly in the mesenchymal interstitial extracellular matrix, rather than in basement membranes. During the first two postnatal weeks, the distribution of laminin shifted to assume the adult pattern, most being located in basement membranes and insoluble under physiological conditions. Analysis of laminin subunit expression showed that both the mRNA for the laminin B chains and the corresponding polypeptides are widely expressed in nerve and other tissues, the mRNA levels decreasing during the first two postnatal weeks as the amount of laminin in the tissue increased. In contrast, the A chain mRNA and polypeptide were undetectable in nerve at any age studied, although they were present in perinatal kidney and placenta. It is proposed that the large amount of soluble laminin present in the developing interstitial extracellular matrix is a consequence of the high levels of expression of laminin mRNA, the subsequent decrease in expression resulting in the adult distribution where most laminin is insoluble within the basement membrane. PMID- 2100264 TI - A cytosolic sperm factor stimulates repetitive calcium increases and mimics fertilization in hamster eggs. AB - Microinjection of cytosolic sperm extracts into unfertilized golden hamster eggs caused a series of increases in cytoplasmic free calcium, Ca2+i, and membrane hyperpolarizing responses, HRs. These HRs and Ca2+i transients are similar to those seen during in vitro fertilization of hamster eggs. The sperm factor that is responsible for causing these effects appears to be of high molecular weight and protein based. Injection of sperm factor activated eggs and mimicked fertilization in causing repetitive HRs in the presence of phorbol esters and in sensitizing the egg to calcium-induced calcium release. Since these effects cannot be mimicked by injecting G-protein agonists or calcium-containing solutions, it seems unlikely that a receptor-G-protein signalling system is involved at fertilization. These data instead suggest a novel signal transduction system operates during mammalian fertilization in which a protein factor is transferred from the sperm into the egg cytoplasm after gamete membrane fusion. PMID- 2100265 TI - Early C. elegans embryos are transcriptionally active. AB - We have developed a nucleotide incorporation assay for run-on transcription in C. elegans embryonic extracts as an approach to characterizing early transcription. The incorporation is primarily polymerase II-catalyzed RNA synthesis, producing transcripts of the expected size range for mRNAs. Incorporation is insensitive to inhibitors of reinitiation, indicating that the activity represents primarily elongation of nascent chains initiated prior to extract preparation. The transcripts produced appear to be unprocessed pre-mRNAs. Hybridization of labeled transcripts from extracts of staged embryos to a set of cloned genes suggests that the specificity of the in vitro reaction accurately reflects developmentally regulated in vivo transcription. Comparative analyses of transcription in extracts from various stages indicate that pregastrulation embryos are active transcriptionally and that the level of transcription per nucleus is approximately constant throughout embryogenesis. Furthermore, most embryonically expressed genes are already being transcribed in pregastrulation embryos. We also demonstrate that the labeled embryonic run-on transcripts can be used as probes to screen for sequences transcribed preferentially in pregastrulation embryos. There appears to be only a small set of such sequences, which could represent a previously unsuspected class of embryonically transcribed genes important for early embryogenesis. PMID- 2100267 TI - Estimation of neuroblast numbers in insect neurogenesis using the lateral inhibition hypothesis of cell differentiation. AB - Cells in the neurogenic region of an insect ectoderm have two alternative fates, making neurons or epidermis. The fates seem to be determined through a laterally inhibitory interaction among cells. That is, initially homogeneous cells are all competent to differentiate into neuroblasts. Once a cell has differentiated as a neuroblast, it inhibits its immediate neighbors from following this pathway. The differentiation process is simulated by a digital computer in a planar array of polygonal domains similar to a cell pattern. We find that the number of cells differentiating as neuronal precursors in insect neurogenesis is that expected under the hypothesis of lateral inhibition of cell differentiation between immediate neighbors. PMID- 2100266 TI - Drosophila neurotactin, a surface glycoprotein with homology to serine esterases, is dynamically expressed during embryogenesis. AB - Drosophila neurotactin is a transmembrane glycoprotein with an apparent molecular mass of 135 x 10(3). Neurotactin is regionally expressed at the cellular blastoderm stage; later in embryogenesis the expression of the protein becomes restricted to cells of the peripheral and central nervous system. Immunocytochemical localization shows neurotactin protein at points of cell-cell contact. Using the anti-neurotactin monoclonal antibody BP-106, a neurotactin cDNA was isolated that encodes a 846 residue polypeptide. The chromosomal location of the neurotactin gene is 73C. The extracellular domain at the carboxyterminal end of the neurotactin protein shows a strong structural and sequence homology to serine esterases without retaining the amino acids forming the active center. Neurotactin therefore belongs to a growing group of proteins including Drosophila glutactin and thyroglobulins that are known to share this serine esterase protein domain motif without retaining the active center of the enzyme. PMID- 2100268 TI - Dental plaques; nature and role in periodontal disease. PMID- 2100269 TI - Characterization of the epidermal growth factor receptor in the gastric mucosa. AB - The effects of epidermal growth factor (EGF), a potent mitogen involved in mucosal protection, are mediated by specific cellular receptors. Here, we present the characteristics and binding properties of EGF receptors in the gastric mucosa. The studies were conducted using cell membranes isolated by subcellular fractionation of rat stomach mucosal scrapings. Specific binding of [125I]-EGF to the membrane preparations was assessed at room temperature for various periods of time and at different pHs. The results showed that the binding was proportional to the incubation time up to 1 h and was not affected by a pH change between 4.0 and 7.0. Scatchard analysis of the binding data infer the presence of 2 binding sites, one of high affinity (Kd = 1.34 nM, Bmax = 34 fmol/mg protein) and the other of low affinity (Kd = 484 nM, Bmax = 2.29 pmol/mg protein). Cross-linking experiments using disuccinimidyl suberate to link the [125I]-EGF to gastric membranes followed by polyacrylamide gel electrophoresis and autoradiography revealed that the major receptor for EGF was a protein of 170 kilodaltons. When the solubilized membranes were subjected to wheat germ agglutinin affinity chromatography, the purified material was found to act as substrate for EGF stimulated phosphorylation. The major component which was labeled by the [gamma 32P]-ATP was also found to be a 170-kilodalton protein. The data are the first to provide evidence that the gastric mucosa possesses a functional EGF receptor and describe its binding characteristics. PMID- 2100270 TI - Comparison of bile salt perturbation of duodenal and jejunal isolated brush border membranes. AB - Rabbit duodenal and jejunal brush-border membrane vesicle integrity, fluidity and passive proton permeability were studied after in vitro exposure to deoxycholate, glycodeoxycholate or taurodeoxycholate. Duodenal and jejunal membrane mean vesicle volume [0.54 (0.05) and 0.54 (0.03) microliters/mg, mean values with SE in parentheses], and proton permeability [6.30 (0.02) x 10(-4) and 5.59 (0.17) x 10(-4) cm.S-1] were similar, while membrane fluidity was slightly, but significantly, greater in jejunal membranes [diphenylhexatriene fluorescence anisotropy, (r0/r)-1 = 0.499 (0.013) and 0.572 (0.012)]. The three bile salts (0.1-5.0 mM) caused concentration-related decreases in vesicle integrity as assessed by [14C]glucose retention at equilibrium. Jejunal membranes were more sensitive at low bile salt concentrations, 0.1 and 0.5 mM. With high concentrations of bile salts, 5 mM, above their critical micelle concentrations, less than 10% of jejunal or duodenal vesicles remained. The bile salts caused concentration-related increases in jejunal membrane fluidity over the range 0.1 1.0 mM bile salt, but duodenal membrane fluidity was only increased at the highest concentration of bile salt. Proton permeability (Pnet) of the membranes was increased by the bile salts (0.1-1.0 mM), and again the jejunal membranes were more sensitive; Pnet increased by approximately 120, 150 and 170 in duodenal, and 150, 220 and 380% in jejunal membranes, with deoxycholate at 0.1, 0.5 and 1.0 mM, respectively. There were no consistent differences in the potency of the unconjugated and conjugated bile salts. The three variables were only significantly correlated for duodenal membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100271 TI - Regression of liver steatosis following gastroplasty or gastric bypass for morbid obesity. AB - 15 consecutive persons aged under 50 with an overweight exceeding 75% were examined clinically, biochemically and with liver biopsy after gastric bypass (7 patients) or gastroplasty (8 patients). After 1 year the occurrence of steatosis had fallen from 73 to 40% which, together with a marked decrease in individual gradings of fatty changes, represented a significant regression of the steatosis. Likewise, discrete inflammatory and granulomatous changes largely disappeared. In no case was fibrosis present. Serum alkaline phosphatases preoperatively increased above normal range in 20% but their mean level was significantly reduced after 12 months of weight loss. Other liver function tests remained normal and stable. In contrast to published experience with jejunoileal bypass operations liver steatosis associated with morbid obesity seems to be morphologically and biochemically reversed together with the weight reduction obtained by gastroplasty or gastric bypass. PMID- 2100272 TI - Postprandial release of cholecystokinin after duodenum-preserving total pancreatectomy is independent of intraluminal pancreatic protease activity in dogs. AB - The effect of meal stimulation, with and without the intraduodenal presence of pancreatic enzymes, on plasma cholecystokinin (CCK) release was studied in order to investigate the role of CCK in the putative feedback mechanism between intraduodenal pancreatic proteases and pancreatic enzyme secretion. Plasma CCK concentrations in response to a semiliquid meal, with and without the supplementation of exocrine pancreatic enzymes, were measured in 8 dogs after duodenum preserving pancreatectomy. With a well-balanced endocrine and exocrine substitution regimen all dogs were kept in good clinical condition, without steatorrhea or significant weight loss, and fasting plasma glucose levels within the normal range. Exocrine supplementation was stopped at least 3 days prior to tests. Basal plasma CCK levels after 3 days without exocrine supplementation (2.5 +/- 0.3 pM) did not significantly differ from the results with supplementation (3.0 +/- 0.5 pM) nor from the preoperative levels (2.3 +/- 0.3 pM). In addition, integrated plasma CCK responses to the meal without exocrine supplementation (330 +/- 37 pM.90 min) were not significantly different from the responses to the meal with exocrine supplementation (303 +/- 49 pM.90 min), or from the postprandial CCK response in the dogs with an intact pancreas preoperatively (390 +/- 100 pM.90 min). It is concluded that the release of CCK in dogs after total pancreatectomy is independent of intraluminal protease activity. It is therefore not likely that CCK mediates the putative feedback mechanism between intraluminal protease activity and pancreatic enzyme secretion in dogs. PMID- 2100273 TI - Varicosis coli totalis: report of a case of idiopathic aetiology. AB - A case of colonic varices manifesting with rectal bleeding in a young patient is presented. There was no evidence of portal hypertension or any other cause. Familial history was also negative. Diagnosis was established by barium enema, colonoscopy and angiography. On colonoscopy, varices involved the entire colon. At operation, dilatation of the subserosal small veins of the entire small and large bowel was confirmed. The patient underwent a subtotal colectomy with ileorectal anastomosis with satisfactory result. PMID- 2100274 TI - Evidence of morphological and functional abnormalities in the hypothalamus of growth-hormone-deficient children: a combined magnetic resonance imaging and endocrine study. AB - Fifty-seven children with growth hormone deficiency and 15 healthy age-matched controls were studied by magnetic resonance imaging (MRI). Of the patients, 36 (63%) had isolated GH deficiency (IGHD) and 21 (37%) multiple pituitary hormone deficiency (MPHD). MRI studies showed a marked reduction in pituitary volume in all patients in comparison with normal controls. Moreover, a striking morphological abnormality with the apparent absence of the pituitary stalk and an ectopic posterior pituitary lobe was detected in 34 of the patients (59%). This pituitary stalk abnormality was detected in 95% of the MPHD patients and in 39% of the IGHD patients. All but one of the patients with a normal pituitary stalk had IGHD. Endocrine evaluation showed no correlation with MRI data: in particular patients with an apparent anatomical interruption of the hypothalamic-pituitary axis showed a variety of patterns of hormonal responses. In conclusion, our study shows a high frequency of hypothalamic-pituitary anomalies in patients with GH deficiency, particularly related with MPHD. However, further studies are needed to improve our understanding of the relationship between MRI and endocrine data. PMID- 2100275 TI - Effect of chronic clonidine treatment on urinary growth hormone excretion and linear growth in children with short stature. AB - Eleven prepubertal children with short stature were treated with clonidine (0.15 mg/m2 daily) for a period of 1 year. The effect of this drug was evaluated on both clinical (growth velocity, height standard deviation scores for chronological age and bone age) and hormonal (urinary growth hormone excretion and insulin-like growth factor I) parameters. Our study shows that long-term clonidine administration in children with short stature did not result in significant differences in growth velocity, height standard deviation scores for chronological age and bone age, insulin-like growth factor I or in urinary growth hormone excretion. PMID- 2100276 TI - Growth response to growth-hormone administration during the decelerating phase of the pubertal growth spurt in short normal children. AB - In order to investigate the value of growth hormone (GH) treatment during late puberty, we studied the effect of human GH (hGH) administration (0.85 +/- 0.30 IU/kg/week; range: 0.44-1.28) on height velocity (HV) after the peak of the pubertal growth spurt in a group of 10 (4 girls and 6 boys) short normal children (GH peak after pharmacological stimulation: 15.5 +/- 2.3 ng/ml) with growth retardation (height: 2.6 +/- 0.3 SD) and puberty Tanner stage 4. A group of 10 untreated children, observed prior to the study, served as controls. The children were regularly measured during their pubertal growth spurt, and HV (cm/year) was calculated every 6 months. The pretreatment evaluation consisted of 2 consecutive 6-month periods characterized by a decrease in HV of at least 25%. In the group of selected children, hGH administration was then initiated and growth variables were evaluated after 6 and 12 months of therapy. Skeletal maturation was evaluated at the beginning as well as after 6 months and 12 months of hGH therapy. In the controls, HV (mean +/- SD) had decreased from 8.8 +/- 1.8 to 4.9 +/- 1.4 cm/year during the pretreatment period (in girls from 7.9 +/- 1.4 to 4.1 +/- 0.6 cm/year and in boys from 9.6 +/- 1.6 to 5.8 +/- 1.2 cm/year). During the following semester, HV was 3.3 +/- 0.8 cm/year (girls: 3.4 +/- 1.0 and boys: 3.2 +/- 0.2 cm/year).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100277 TI - Production of interleukin-1 alpha and interleukin-2 by mononuclear cells from children with growth delay in relation to the degree of growth hormone deficiency: effects of substitutive treatment. AB - Interleukin-1 alpha (IL-1 alpha) and interleukin-2 (IL-2) levels were measured by radioimmunoassay in samples of conditioned medium from mononuclear cells taken from 20 normal subjects (14 adults ranging in age from 20 to 45 years and 6 children ranging in age from 3 to 11 years) and from 49 children with growth delay. Cultures were performed with 10(6) cells/ml in medium containing 1% normal human serum and 4.8 g/l phytohemagglutinin M. The incubation was performed for 48 h in an atmosphere containing 5% CO2. In normal subjects, the production of IL-1 alpha was 38.5 +/- 9.8 fmol/ml of conditioned medium (mean +/- SEM) in 14 adults and 41.6 +/- 3.0 fmol/ml in 6 children. The production of IL-2 was 46.9 +/- 6.5 and 57.3 +/- 10.5 fmol/ml, respectively. In the 16 patients with growth hormone (GH) deficiency studied before treatment, the production of ILs was significantly decreased in relation to the degree of deficiency. We observed a positive correlation between the production of IL-1 alpha and the values of insulin-like growth factor I but not with serum GH values. IL-1 alpha production was normalized after 15 days of substitutive GH therapy and IL-2 was normalized after 3 months of therapy. In 10 other patients with GH deficiency (4 with total and 6 with partial isolated GH deficiency) studied after long-term GH treatment (5 months or more), the mean of IL production was not significantly different from that of GH-deficient children treated for 3 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100278 TI - Reproductive endocrine functions in men with primary hypothyroidism: effect of thyroxine replacement. AB - Reproductive endocrine functions were studied in men with primary hypothyroidism during the hypothyroid phase and after achieving euthyroid status with thyroxine substitution therapy. Hypergonadotropism [luteinising hormone (LH), 18.7 +/- 7.3 IU/l; follicle-stimulating hormone (FSH), 6.3 +/- 2.0 IU/l], low serum testosterone (6.1 +/- 2.8 nmol/l), low serum sex-hormone-binding globulin (SHBG; 13.2 +/- 2.0 nmol/l) and subnormal testosterone response to human chorionic gonadotropin hCG; (30% increase in serum testosterone following hCG) observed during the hypothyroid phase were restored to normal (LH, 7.2 +/- 2.0 IU/l; FSH, 2.7 +/- 0.9 IU/l; testosterone, 12.9 +/- 2.7 nmol/l; SHBG, 26.5 +/- 8.4 nmol/l, and 2-fold increase in serum testosterone following hCG) with thyroxine substitution therapy. Some improvement in sperm count and motility was also observed. PMID- 2100279 TI - Blood-spotted filter paper measurements of thyroxine and thyroid-stimulating hormone in the follow-up of children with congenital hypothyroidism. AB - Neonatal screening for congenital hypothyroidism using T4 and TSH measurements from blood-spotted filter paper is a well-established method. However, it has not been used to monitor T4 and TSH concentrations in the follow-up of these children. In 22 treated children with congenital hypothyroidism whom we follow up in our Clinic, T4 and TSH concentrations were concomitantly measured from venous blood and blood-spotted filter paper. There was a significant positive correlation between both T4 and TSH measurements from venous blood versus blood spotted filter paper (r = 0.7, p = 0.001; r = 0.78, p less than 0.05). Filter paper T4 values above 7 micrograms/dl could exclude hypothyroxinemia in 98% of the specimens. When TSH values were above 10 microU/ml, it was confirmed in 94% of the specimens, and when they were above 20 microU/ml, it was confirmed in 97% of the specimens. Measurements of both filter paper T4 and filter paper TSH did not increase the reliability of the results obtained by examining the two hormones separately. We therefore suggest that filter paper T4 and/or TSH measurements have distinct advantages in monitoring the treatment of children with congenital hypothyroidism. It can be performed in the community, enabling assistance in the follow-up of children in remote areas who are unable to show up for serum tests. The results are obtained quickly and allow improved follow-up by providing useful information such as excluding hypothyroxinemia or suggesting the possibility of noncompliance, and by a psychological effect on parents. However, they cannot replace serum T4 and TSH measurements altogether. PMID- 2100280 TI - Effect of thyroid hormone on epidermal growth factor-like immunoreactivity and growth velocity in cynomolgus monkeys. AB - To examine the potential role of epidermal growth factor (EGF) in mediating the effects of thyroid hormone on linear growth, we measured serum EGF levels by RIA in cynomolgus monkeys before and during methimazole-induced hypothyroidism, and after 9 weeks of T4 replacement at different doses. Ten castrated prepubertal monkeys were rendered hypothyroid by methimazole (0.0125% in drinking water for 12 weeks). Methimazole was continued, and T4 was then administered for 9-week intervals. Six weeks elapsed between successive T4 doses. The sequence of different T4 doses for each animal was random. Serum EGF level was measured at baseline and at the end of each treatment period with a newly developed RIA using a polyclonal antiserum against human recombinant EGF. Serum EGF level correlated significantly with the level of serum thyroxine but not with serum triiodothyronine, over the thyroxine dosage range of 1-4 micrograms/kg/day (r = 0.41, p less than 0.005). Lower-leg growth rate correlated significantly with serum EGF level over this same thyroxine dosage range (r = 0.41, p less than 0.005). These data are consistent with the hypothesis that EGF may mediate some of the effects of thyroid hormone on skeletal growth. PMID- 2100281 TI - Epidermal growth factor receptors in cultured human trophoblast cells from first- and third-trimester placentas. AB - Epidermal growth factor (EGF) receptors were studied during the in vitro differentiation of human trophoblast cells from first- and third-trimester placentas. Cytotrophoblasts were isolated by enzymatic digestion and purified on a discontinuous Percoll gradient. As analyzed by flow cytometry, 5% of the cells are in the G2M phase in the early placenta and 0% in the term placenta. In culture, the cytotrophoblasts at both gestational ages flatten out, aggregate, and fuse together to form syncytiotrophoblasts. This in vitro morphological differentiation is associated with a threefold increase in the ability to bind specifically 125I-EGF. Trophoblastic cells from the term placenta have a significantly (p less than 0.005) higher receptor number (68.6 +/- 9.5 fmol/mg protein) for EGF after 2 days of culture than first-trimester cytotrophoblasts (35.8 +/- 2.3 fmol/mg protein). Scatchard plot analysis revealed two classes of binding sites with a similar affinity in both first-trimester and term placentas (9.5 x 10(9) M-1 for the high-affinity, 0.5 x 10(9) M-1 for the low affinity site). When 125I-EGF was affinity cross-linked to cytotrophoblasts, the receptors appeared as a specific band with a molecular weight of 180 kD in SDS-PAGE. This study demonstrates that the culture of cytotrophoblasts offer an appropriate model to study the modulation of EGF receptors. PMID- 2100282 TI - Evaluation of a peptide family encoded by the calcitonin gene in selected healthy pregnant women. A longitudinal study. AB - We conducted a longitudinal study on serum levels of peptides encoded by the calcitonin gene before conception, every month during pregnancy, and 24 h and 5 days after delivery in 26 healthy women. Only subjects fulfilling optimality criteria according to the literature were included. Blood samples for ionized calcium, total (tCT) and extractable (exCT) calcitonin, katacalcin, and calcitonin gene-related peptide (CGRP) were collected. We found no significant changes of ionized calcium, tCT, exCT, and katacalcin levels, while CGRP serum levels showed a significant increase during pregnancy and a fall to preconceptional values after delivery. Since variations of calcitonin levels did not occur in our selected pregnant women, we conclude that thyroidal C cell secretion is not increased during pregnancy. Our data suggest that calcitonin is not involved in the modifications of mineral homeostasis occurring in pregnancy. In addition, the variations of CGRP serum levels we found suggest that such a hormone participates in circulation modifications of pregnant women. PMID- 2100283 TI - Osteoporosis and diabetes: lessons from the diabetic BB rat. AB - The spontaneously diabetic BB rat was used to study the effect of diabetes on bone. Short-term diabetes (3-4 weeks) resulted in a state of low bone turnover, characterized by a severe decrease in osteoblast/osteoid surface and bone mineral apposition rate on histology, and in serum osteocalcin concentrations. If diabetes was long-term (12 weeks), the parameters of low bone formation were associated with histological evidence of osteoporosis and a decreased bone strength; the relative bone calcium concentration remained normal in diabetes. We conclude that long-standing diabetes results in a low-turnover osteoporosis. PMID- 2100284 TI - Effect of vasopressin and naloxone alone and in combination on cortisol secretion after dexamethasone pretreatment. AB - In order to further examine the possible role of endogenous opioid peptides and vasopressin in the phenomenon of dexamethasone nonsuppression, we studied the effect of naloxone, vasopressin, and vasopressin-naloxone combination on cortisol secretion following dexamethasone pretreatment. Nine healthy males were given 1 mg dexamethasone at 23.00 h. The following day starting at 12.30 h and at 90-min intervals they received intravenously naloxone (0.2 mg/kg), arginine vasopressin 3 units, or the two drugs combined. The order of drug administration was counterbalanced using a Latin square design. Blood samples were drawn at 15-min intervals, and plasma aliquots were assayed for cortisol and dexamethasone. Naloxone failed to induce an escape from dexamethasone suppression. Four of the 9 subjects responded with an escape from dexamethasone suppression in response to vasopressin alone. The observed variability in response to vasopressin was unrelated to dexamethasone plasma levels but was associated with a decrease in systolic blood pressure. Peak cortisol levels were lowest in response to naloxone and highest in response to vasopressin. There was no evidence of an increased cortisol response to the coadministration of naloxone with vasopressin compared to vasopressin alone. These results fail to implicate an opioidergic mechanism in the pathophysiology of dexamethasone nonsuppression. PMID- 2100285 TI - Vascular mediation of gastric mucosal damage and cytoprotection. AB - This review addresses questions surrounding the role of the mucosal circulation in damage and protection against chemical injury to the stomach. The modern history of the topic is briefly summarized, and widely used methods are appraised critically. The role of the circulation is examined in mucosal injury and in cytoprotection, and a new conceptual model is described which involves the vasculature and inflammatory mediators. PMID- 2100286 TI - Effect of lesions of areas of brain--stimulation reward of one region of brain on operant behaviour for receiving electrical stimulation into sites of another region and on operant behaviour for food reward. AB - It was aimed to study the effects of lesions of a self-stimulation (SS) area of one region of brain on the SS of another region, and on feeding behaviour in adult Wistar rats (males). The two regions proposed for study were the lateral hypothalamus (LH) and the substantia nigra-ventral tegmental area (SN-VTA). The objective was to elucidate whether each region had its own neural organization for SS behaviour or not, and whether the neural substrates of SS behaviour and feeding behaviour were one, or separate. Four bipolar electrodes were implanted bilaterally in LH and SN-VTA in each rat, and their SS pedal press rates for rewarding electrical stimulations were characterised. The rats were also trained in operant conditioning paradigm for receiving reward of food grains in FR-30 schedule. Their free-field food intake in home cages was measured. Later, electrolytic lesions of the four electrode sites were made one after another at 2 day intervals through the same biopolar electrodes. After each lesioning, the SS of the same and of the other electrode sites, and the operant performance of FR 30 food reward schedule, and daily free-field food intake (in home cage) were determined. Lesions of the LH SS site always disrupted SS-of contralateral LH but not of SN-VTA SS. Lesions of SN-VTA had not modified contralateral SN-VTA SS. A study of effects of ipsilateral lesions of LH SS site on SN-VTA SS, or of lesions of SN-VTA SS site on LH SS, revealed a range of changes, as were also effects on the FR-30 operant performance and daily food intake. Medium size lesions of SS area made in one region affected the SS of that area but not usually the SS of the other region. Large lesions of one region affected the SS of the other regions also. With large lesions, feeding behaviour also was affected, firstly of the operant type and secondly the free-field type. PMID- 2100287 TI - Effect of cold challenge on alveolar capillary blood volume in normal individuals. AB - The effect of immersion of both the hands and the feet in water at 10 degrees C on lung transfer factor for carbon monoxide (Tlco) and on pulmonary capillary blood volume (Vc) was investigated in 20 normal young adult males immediately, 60 min and 120 min after the end of the cold challenge. Vc was significantly reduced immediately and the reduction was aggravated at 60 min. Tlco was significantly reduced only at 60 min. All the values returned to baseline at 120 min. It is concluded that the cold-induced changes in Tlco and Vc are physiological responses and not unique to patients with Raynaud's phenomenon as suggested by some workers. PMID- 2100289 TI - Development of software for computer-assisted interpretation of pulmonary function tests. AB - This paper describes the need for the development of software for computer interpretation of Pulmonary Function Tests based on equations derived from Indian populations, and the development strategies adopted. The decision flowcharts are given. The present limitations and areas of ongoing refinement of the program are discussed. PMID- 2100288 TI - Alteration in the levels of pyrazinamide in pleural fluid following simultaneous administration of prednisoline in patients of tubercular pleural effusion. AB - 20 Patients of tuberculous pleural effusion were administered a combination of pyrazinamide (30 mg/kg) + isoniazid (300 mg) orally for 7 consecutive days and pyrazinamide was estimated by spectrophotometric method in serum and pleural fluid. Prednisolone was added to the above regimen for next 7 consecutive days and pyrazinamide was again estimated. The level of pyrazinamide in pleural fluid was 23.4 +/- 1.2 (micrograms/ml). Following addition of prednisolone the level increased (27.6 +/- 1.3) significantly (P less than 0.001). The serum pyrazinamide level was not influenced by simultaneous administration of prednisolone. The pleural fluid/serum pyrazinamide ratio was increased from 0.465 to 0.542 by the addition of prednisolone to therapeutic regimen. PMID- 2100290 TI - Quantitative evaluation of muscle relaxation induced by Kundalini yoga with the help of EMG integrator. AB - The present work is aimed to quantify the degree of relaxation of muscle under the effects of Kundalini Yoga with the help of EMG integrator. The data collected from 8 individuals (4 males 4 females) on the degree of muscle relaxation at the end of meditation revealed a significantly decreased muscle activity amounting to 58% of the basal level in both the sexes. PMID- 2100291 TI - Brainstem auditory evoked potential response in pernicious anaemia. PMID- 2100292 TI - pH of semen in normal and abnormal ejaculates. PMID- 2100293 TI - Presence of gold in semen. PMID- 2100294 TI - Pentylene tetrazol induced monoamine changes in rat brain. PMID- 2100295 TI - How mobility officers assess need for mobility training. AB - Little is known about how Mobility Officers (O&M specialists) assess the training needs of visually impaired clients. In principle, these assessments may be based on estimates of existing travel skills, and the visual and psychological status of clients. In this study, the priority-for-training ratings made when residents arrived at a residential rehabilitation centre were correlated with measures of clients' feelings when travelling, and with visual status. The feelings checklist contained twenty-one items which clients themselves identified as describing how they felt on a journey. Priority for training was related to six of these feelings, which together accounted for 60.24% of the variance of training priorities. These data suggest that Mobility Officers do respond to how their clients are feeling when assessing their need for training. Clinical measures of visual status, surprisingly, were not directly involved in the assessments. However, lower peripheral field status, which could not have been known to Mobility Officers, was significantly correlated with assessments, accounting for a further 15.57% of the variance of priorities; in total, therefore, 75.81% of the variance of assessments were accounted for by the combination of psychological factors, and this visual factor. It is suggested that the latter correlation was due to the effects of an intervening variable. This may have been some aspect of mobility performance, which depends particularly on lower peripheral visual information for its execution. PMID- 2100296 TI - Helping postacute traumatically brain injured clients return to work: three case studies. AB - This paper presents three case studies of individuals who had sustained a severe brain injury and who are clients of a return to work programme emphasizing a supported employment approach. The case studies illustrate the types of interventions which are utilized, including job placement; job site and off-site training, advocacy, and compensatory strategies; and ongoing assessment and maintenance of social and productive gains in order to assist with job retention. The results of the case studies may be generalized to the population of brain injury survivors who require intensive and long-term intervention and support in order to return to employment. PMID- 2100297 TI - Health care delivery and professional effectiveness: centralization, staff admission, surgical performance and decision making. AB - Professional power and professional effectiveness in hospitals is a little investigated but very critical phenomenon. The problem with any investigation on power is the many variables which are involved and the complex way in which they manifest themselves. This paper tests the hypothesis of potential redundancy among these variables. The null hypothesis was rejected in favour of the alternative hypothesis, concluding that the original nine variables contained redundancies and could be replaced with four non-redundant factors. The implications for future research in this area are stated. PMID- 2100298 TI - Traumatic brain injury and marital relationships: a literature review. AB - This is a review of the research regarding the effects of traumatic brain injury (TBI) on the marital relationship. Individuals who have withstood a severe traumatic brain injury usually exhibit a range of cognitive and behavioural disabilities. Typical problems outlined in the research include: attention and concentration deficits, memory and information-processing deficits, judgement and perception difficulties. While these impediments pose problems for community re integration, they may become sources of difficulty for the spouse. The following report critically examines the literature on the effects of head injury on marital relationships. This research has demonstrated that spouses' reactions to TBI include feelings of anxiety, isolation, and loss. In addition, this literature review shows that there is a dearth of research that has regarded the individual with TBI to be a valid source of information, or has considered women with TBI in a marital situation. PMID- 2100299 TI - Psychosocial adjustment of persons with spinal cord injury. PMID- 2100300 TI - An evaluation of a group treatment programme for stroke patients with perceptual deficits. PMID- 2100301 TI - Blind adolescents' perceptions of parental attitudes. PMID- 2100302 TI - Filtration of water from mother to conceptus via paths independent of fetal placental circulation in sheep. AB - 1. Four pregnant ewes were operated on at 121-126 days of gestation. An electromagnetic flow sensor and an inflatable occluder were placed on the maternal common internal iliac artery. The ovarian arteries and veins were ligated. Indwelling catheters were placed in a maternal femoral artery and uterine vein and in the amniotic and allantoic fluids. An inflatable occluder was placed around the umbilical cord, close to the fetal abdomen. 2. Eight to nine days after surgery, the cord was occluded, the fetus killed and uterine blood flow reduced to one-quarter of its control value. The rate of water loss from the uterine circulation was calculated from blood flow and the venoarterial difference in blood osmolality. The amniotic and allantoic fluids were made hypertonic by infusion of 2 l into each sac of a solution of 1.5 mol of mannitol per litre of saline. The rate of water loss from the maternal uterine circulation was then measured five times over the next 4.5 h. 3. The combined filtration coefficient surface area product of the interfaces between maternal blood and the amniotic and allantoic sacs, normalized per kilogram fetal body weight, was (2.8 +/- 0.5) x 10(-6) cm3 s-1 kPa-1 kg-1 (mean +/- S.E.M). PMID- 2100303 TI - Magnesium transport in ferret red cells. AB - 1. Mg2+ efflux from ferret red cells into a nominally Mg2(+)-free medium is 41 +/ 2 mumol (l cell)-1 h-1. The properties of Mg2+ transport can be measured in these cells without the need for Mg2+ loading. 2. Amiloride, quinidine, imipramine and external divalent cations partially inhibit Mg2+ efflux. Maximal inhibition by these agents is about 60-70% suggesting that at least two Mg2+ transport pathways exist. 3. As external Na+ is replaced by choline or N-methyl-D glucamine Mg2+ efflux is first stimulated, reaching a peak when external [Na+] ([Na+]o) is about 10 mM, and then inhibited. Mg2+ transport reverses direction so net Mg2+ uptake occurs when [Na+]o is reduced below 1 mM. 4. Mg2+ efflux is stimulated when 0.1 mM-EDTA is added to the medium only when [Na+]o is low. 5. Reduction of cell ATP content to about 20 mumol (l cell)-1 by treating cells with 2-deoxyglucose stimulates Mg2+ efflux measured over the 2 h period following depletion. 6. Substantial Mg2+ influx can be observed in ferret red cells when they are incubated in media containing 10 mM-Mg2+. Influx is stimulated by reducing [Na+]o to 10 mM. Further reduction of [Na+]o to below 1 mM reduces Mg2+ uptake. A component of uptake is inhibited by external Co2+. 7. Na(+)-Mg2+ antiport may account for a substantial component of Mg2+ transport in ferret red cells. The direction of transport can be reversed by sufficiently lowering [Na+]o or by increasing external [Mg2+]. Analysis of the conditions at which transport reverses direction suggests transport with a stoichiometry of 1 Na+:1 Mg2+. Antiport with this stoichiometry would also explain maintenance of the physiological level of intracellular ionized Mg2+ in these cells. PMID- 2100304 TI - Voltage-gated potassium currents in myelinating Schwann cells in the mouse. AB - 1. The whole-cell variation of the patch-clamp technique was used to record ionic currents in Schwann cells obtained from enzyme-treated mouse sciatic nerves before and after the onset of myelination. 2. Only outward currents were evoked in embryonic Schwann cells, which had no myelin, at membrane potentials more positive than -40 mV. Neonatal myelinating cells developed depolarization activated outward currents and hyperpolarization-activated inward currents. For large hyperpolarizations below -160 mV, inward currents exhibited a sag following a peak which appeared to be mainly due to Na+ blockade. 3. Membrane potentials of neonatal myelinating cells were more negative than those of embryonic cells. The depolarization of the membrane potentials per 10-fold increase in external K+ concentrations in neonatal myelinating cells was 57 mV which fits the Nernst equation for a K+ electrode. 4. Quinine (0.5-2 mM) blocked the outward currents in embryonic cells and Ba2+ (2 mM) blocked both outward and inward currents in neonatal myelinating cells leaving quinine-sensitive outward currents of the embryonic type. External Cs+ (5 mM) blocked mainly inward currents and internal Cs+ blocked outward currents. 5. Developmental changes of these voltage-gated K+ currents in myelinating cells showed that Ba2(+)-sensitive K+ currents disappeared rapidly during the first week of life in association with the membrane potential becoming more positive. In contrast, quinine-sensitive outward K+ currents of the embryonic type disappeared slowly during the first 3-4 weeks after birth. 6. It is concluded that neonatal myelinating Schwann cells developed new voltage-gated K+ channels, which are Ba2(+)-sensitive and set a new membrane potential, in addition to the voltage-gated K+ channels of embryonic type. The Ba2(+)-sensitive K+ channels in myelinating cells were suggested to play an important role in siphoning K+ ions accumulated in periaxonal space during nerve activities. PMID- 2100305 TI - The contractile response during steady lengthening of stimulated frog muscle fibres. AB - 1. Steady lengthenings at different velocities (0.025-1.2 microns/s per half sarcomere; temperature 2-5.5 degrees C) were imposed on isolated frog muscle fibres at the isometric tetanus plateau by means of a loudspeaker motor. The lengthening at the sarcomere level was measured by means of a striation follower either in fixed-end or in length-clamp mode. The force response was measured by a capacitance gauge transducer (resonance frequency 50 kHz). Preparations showing gross non-homogeneity during lengthening were excluded. 2. A steady tension was in all cases reached after about 20 nm per half-sarcomere of lengthening. Tension during this steady phase rose with speed of elongation up to 0.25-0.4 micron/s per half-sarcomere, when tension was 1.9-2 times isometric tetanic force (T0). Further increase in speed produced only very little increase in the steady tension. 3. During the transitory phase, before steady tension was reached, the tension rose monotonically if speed of lengthening was less than 0.25-0.3 micron/s per half-sarcomere; at higher speed the tension rose above the steady level, reaching a peak when extension was 10-14 nm per half-sarcomere, and then fell to the steady level. Tension at the peak continued to rise with speed of lengthening above 0.3 micron/s per half-sarcomere. 4. During the tension rise within the transitory phase of force response the segment elongated at a speed 15 20% lower than that imposed on the whole fibre, as a consequence of tendon compliance. 5. During the steady phase, non-homogeneity of lengthening speed began above a speed of lengthening which varied from fibre to fibre. At speeds below this value, segments elongated at the same speed as that imposed on the fibre. 6. Tension responses to large step stretches (up to 12 nm per half sarcomere), applied at the plateau of isometric tetanus, showed that the instantaneous elasticity of contractile machinery is not responsible for the limit in force attained with high-speed lengthening. 7. Instantaneous stiffness was determined during the steady state of force response by superposing small steps (less than 1.5 nm per half-sarcomere) on steady lengthening at different velocities. Stiffness was 10-20% larger during lengthening than at the plateau of isometric tetanus and remained practically constant, independent of lengthening velocity, in the range of velocities used. 8. The results indicate that steady lengthening of a tetanized fibre induces a cross-bridge cycle characterized by fast detachment of the cross-bridge extended beyond a critical level.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2100306 TI - Maximum velocity of shortening of three fibre types from horse soleus muscle: implications for scaling with body size. AB - 1. To explore how maximum velocity of shortening (Vmax) of fibres varies within one muscle and how Vmax varies with body size, we measured Vmax of muscle fibres from soleus muscle of a large animal, the horse. 2. Vmax was determined by the slack test on skinned single muscle fibres at 15 degrees C during maximal activation (pCa = 5.2). The fibre type was subsequently determined by a combination of single-cell histochemistry and gel electrophoresis of the myosin light chains. 3. Vmax values for the type I, IIA and IIB muscle fibres were 0.33 +/- 0.04 muscle lengths/s (ML/s) (+/- S.E.M., n = 6), 1.33 +/- 0.08 ML/s (n = 7) and 3.20 +/- 0.26 ML/s (n = 6), respectively. It is likely that the large range in Vmax is due to differences observed in the myosin heavy chains and light chains associated with the three fibre types. 4. Comparison of Vmax over a 1200 fold range (450 kg horse vs. 0.38 kg rat) of body mass (Mb) suggests that slow fibres scale more dramatically (Mb-0.18) than do fast glycolytic fibres (Mb 0.07). This difference may enable the slow fibres to work at high efficiencies in the large animal while the fast fibres can still generate a large mechanical power when necessary. PMID- 2100307 TI - Guinea-pig megakaryocytes can respond to external ADP by activating Ca2(+) dependent potassium conductance. AB - 1. The responses of megakaryocytes to adenosine diphosphate (ADP) were studied using whole-cell patch electrodes and a Ca2(+)-sensitive fluorescent dye, Fura-2. Megakaryocytes (diameter, 17-42 microns) were mechanically dissociated from the bone marrow of adult guinea-pigs and ADP (1-10 microM) was pressure-applied to megakaryocytes under recording. 2. In megakaryocytes immersed in standard saline, ADP evoked an obvious outward current at a membrane potential of -63 mV. The current was identified as a K(+)-carried current, since the reversal potential depended distinctly on the external K+ concentration, but it showed no changes after removal of external Na+. The amplitude of evoked K+ currents showed considerable intercell variation, which is presumably due to differences of current density in the membrane. 3. During application of ADP, the evoked K+ current was not sustained but slowly decayed to become negligible within 10-20 s, suggesting the appearance of desensitization. The response of the megakaryocyte to ADP recovered slowly and returned to an original level after 4-5 min of continuous washing. 4. When the intracellular free Ca2+ concentration ([Ca2+]i) was measured using the Ca2(+)-sensitive fluorescent dye, Fura-2, application of 10 microM-ADP induced an increase of [Ca2+]i by about 5-fold, which was followed by a gradual decay to the original level within 30-50 s. Roles of internal Ca2+ for activating the K+ current were confirmed by observing (1) enhancement of evoked currents by the use of internal saline containing no Ca2+ chelators and (2) generation of prolonged K+ current by application of a Ca2+ ionophore, A23187, to the megakaryocyte. 5. In a fraction of the megakaryocytes, spontaneous hyperpolarization of the resting membrane potential was observed. The hyperpolarization seemed to result from the activation of K+ channels in the membrane, which was caused by spontaneous release of Ca2+ from the internal storage site. 6. It was concluded that megakaryocytes of the guinea-pig can respond to external ADP by increasing [Ca2+]i and consequently by activating Ca2(+)-dependent K+ channels in the membrane. PMID- 2100308 TI - The osmoreceptor complex in the rat: evidence for interactions between the supraoptic and other diencephalic nuclei. AB - 1. Experiments were undertaken to provide evidence for the existence of a circuit of neuronal interconnections between the supraoptic nucleus (SON), the ventral anteroventral third ventricular region (including the organum vasculosum of the lamina terminalis; ventral AV3V) and the median preoptic nucleus (MnPO), and to determine the importance of these connections in the osmotic control of the neuronal activity of the SON. Extracellular recordings were made in the urethane anaesthetized male rat from neurones in one of these three sites, while the other two sites were electrically stimulated. 2. During recording from the SON, electrical stimulus pulses applied either to the ventral AV3V or to the MnPO were followed by orthodromic excitation (OD+) or initial short-duration inhibition followed by long-duration excitation (OD- +) of most SON neurones (44/48). The latency of OD+ or OD+ component of OD- + response produced by electrical stimulation of the MnPO was significantly (paired t test, P less than 0.01) shorter than that by the stimulation of the ventral AV3V. None of the neurones we recorded in the SON was activated antidromically by stimulation of either the ventral AV3V or the MnPO. Pressure injection of lidocaine (10%, 50 nl) into the MnPO reversibly depressed the OD+ effect after stimulation of the ventral AV3V in all the SON neurones tested (11/11), while injection of lidocaine into the ventral AV3V did not affect the OD+ effect after stimulation of the MnPO in most neurones (7/9). Both types of observation are consistent with the presence of an excitatory input to SON through the MnPO. 3. Pressure injection of lidocaine into both the ventral AV3V and the MnPO reversibly blocked the activation of SON neurones following an I.P. injection of 1.5 M-NaCl (1 ml) (ventral AV3V 11/11; MnPO, 10/10 cells tested). Injection of lidocaine at both sites, however, did not prevent activation of SON neurones by hypovolaemia (2 ml of blood was withdrawn through a cannula in the right atrium: ventral AV3V, 4/5; MnPO, 4/4 cells tested). The integrity of connections in the ventral AV3V and MnPO thus appeared to be essential for osmotic activation of the SON. 4. Of the 119 ventral AV3V neurones which were tested for their response to electrical stimulation of the SON, forty-nine neurones showed orthodromic excitation (OD+; n = 33) or initial inhibition followed by excitation (OD- +; n = 16). Thirty of the forty-nine OD+ or OD- + neurones also showed antidromic excitation (AD) after electrical stimulation of the MnPO.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2100309 TI - Convergence of Ia fibres from synergistic and antagonistic muscles onto interneurones inhibitory to soleus in humans. AB - 1. The possibility that Ia afferent fibres from the gastrocnemius medialis (GM) and from the tibialis anterior (TA) muscle could converge on to a single interneuronal pool inhibitory to the soleus motoneurones was investigated. 2. The soleus H reflex, evoked by tibial nerve stimulation in the popliteal fossa, was conditioned by separate or combined stimulation of the nerves to the GM or TA muscles. Stimulus intensity was below the motor threshold (MTh), and the conditioning-test intervals were such as to evoke short-latency inhibition of the soleus H reflex. Care was taken to avoid current spread and artifacts connected with the closeness in time and space of the conditioning and test stimuli. 3. Separate stimulation of both GM and TA nerves was able to induce significant inhibitory effects on the H reflex amplitude at stimulus strengths larger than 0.75 x MTh, on the average. Combined stimulation of the two nerves was able to reduce the H reflex at lower stimulus strengths, at which either nerve was ineffective alone. 4. Conditioning stimulus strengths close to the MTh reduced the H reflex to approximately 80% of the control value, both on single and combined stimulation, i.e. saturation of the inhibitory effect was found. 5. By extrapolating the regression line through the normalized data from all subjects, it was assumed that the smallest stimulus strength necessary to drive the inhibitory interneurones to threshold was, on the average, 0.5 and 0.6 x MTh, on combined and separate nerve stimulation, respectively. 6. Tonic voluntary activation of the soleus abolished the inhibitory effects of both separate and combined stimulations. This was tested on the H reflex, on the rectified and averaged EMG, and on the peristimulus histogram of single motor unit discharge. 7. The findings strongly suggest the existence of spatial summation of the effects from GM and TA muscle at the level of a single interneuronal pool. Most probably, the responsible afferent fibres are group I spindle afferents, and the interneurones those mediating the reciprocal inhibition. The data do not support the notion of parallel pathways, exclusive to each nerve. PMID- 2100310 TI - Role of actin and myosin in the control of paracellular permeability in pig, rat and human vascular endothelium. AB - 1. We have investigated the endothelial actomyosin system with particular emphasis on its possible role in actively opening a paracellular route for permeability. 2. Actin and myosin comprised 16% of total endothelial protein with a molar actin/myosin ratio of 16.2 which is close to the actin/myosin ratio of muscle (studies on freshly isolated pig pulmonary arterial endothelial cells, PAEC). 3. By immunocytochemistry at the light and electron microscope levels the bulk of actin and myosin was colocalized in close vicinity to the intercellular clefts of both micro- and macrovascular endothelial cells in situ and in vitro. 4. Calcium-ionophore-induced rise in permeability of human umbilical venous endothelial cells (HUVEC) and PAEC monolayers grown on filters in a two-chamber permeability system was caused by opening of intercellular gaps. Gap formation depended on the rise in intracellular Ca2+ and could be blocked by the calmodulin binding drugs trifluperazine (TFP) and W7. 5. In skinned monolayers of cultured PAEC and in isolated sheets of HUVEC gap formation was shown to require ATP and occurred only when free myosin binding sites were available on endothelial actin filaments (experiments with myosin subfragment 1 modified by N-ethylmaleimide, S1 NEM). 6. These experiments suggest that actin and myosin in endothelial cells play a central role in regulating the width of the intercellular clefts, thereby controlling the paracellular pathway of vascular permeability. PMID- 2100311 TI - Perceived pitch of vibrotactile stimuli: effects of vibration amplitude, and implications for vibration frequency coding. AB - 1. The effect of changes in amplitude on the perceived pitch of cutaneous vibratory stimuli was studied in psychophysical experiments designed to test whether the coding of information about the frequency of the vibration might be based on the ratio of recruitment of the PC (Pacinian corpuscle-associated) and RA (rapidly adapting) classes of tactile sensory fibres. The study was based on previous data which show that at certain vibration frequencies (e.g. 150 Hz) the ratio of recruitment of the PC and RA classes should vary as a function of vibration amplitude. 2. Sinusoidal vibration at either 30 Hz or 150 Hz, and at an amplitude 10 dB above subjective detection thresholds was delivered in a 1 s train to the distal phalangeal pad of the index finger in eight human subjects. This standard vibration was followed after 0.5 s by a 1 s comparison train of vibration which (unknown to the subject) was at the same frequency as the standard but at a range of amplitudes from 2 to 50 dB above the detection threshold. A two-alternative forced-choice procedure was used in which the subject had to indicate whether the comparison stimulus was higher or lower in pitch (frequency) than the standard. 3. Marked differences were seen from subject to subject in the effect of amplitude on perceived pitch at both 30 Hz and 150 Hz. At 150 Hz, five out of the eight subjects reported an increase in pitch as the amplitude of the comparison vibration increased, one experienced no change, and only two experienced the fall in perceived pitch that is predicted if the proposed ratio code contributes to vibrotactile pitch judgements. At 30 Hz similar intersubject variability was seen in the pitch-amplitude functions. 4. The results do not support the hypothesis that a ratio code contributes to vibrotactile pitch perception. We conclude that temporal patterning of impulse activity remains the major candidate code for pitch perception, at least over a substantial part of the vibrotactile frequency bandwidth. PMID- 2100312 TI - Submandibular responses to stimulation of the parasympathetic innervation in bursts in the anaesthetized ferret. AB - 1. Submandibular salivary and vascular responses to different patterns of stimulation of the parasympathetic innervation have been investigated in anaesthetized ferrets in the presence and absence of atropine. 2. At low stimulus frequencies likely to fall within the physiological range (0.5-2.0 Hz continuously; 5.0-20.0 Hz in 1 s bursts at 10 s intervals) secretion of fluid and protein were both potentiated by the bursting pattern of stimulation and the latency of the secretory response was reduced. Over a somewhat lower range (0.5 1.0 Hz continuously; 5.0-10.0 Hz in bursts) the submandibular vascular response was also significantly potentiated by employing this intermittent pattern of stimulation. Above these frequency ranges no such potentiation occurred. 3. Pre treatment with atropine (2.0 mg kg-1) blocked the submandibular secretory responses to stimulation of the chorda-lingual nerve at these low frequencies and the residual responses at higher frequencies were not significantly affected by changing the pattern of stimulation. The vascular response was somewhat reduced after atropine but that which persisted was enhanced by stimulating in bursts. 4. It is concluded that the release of some transmitter from postganglionic terminals in the submandibular gland of the ferret must be potentiated by the arrival of action potentials at short intervals and possible mechanisms are considered. PMID- 2100314 TI - Variations in blood flow on mandibular glandular secretion to autonomic nervous stimulations in anaesthetized dogs. AB - 1. Continuous stimulation of the preganglionic parasympathetic nerve (the ramus communicans of the mandibular ganglion) for 1-2 min at supramaximal voltage (5 V) and pulse duration (1 ms) increased salivary gland arterial inflow and this was accompanied by copious salivary secretion. The responses were recorded continuously during the period of stimulation. The frequency for initiating the responses was 0.5 Hz. Maximal responses occurred at 16 Hz. The response coefficient of arterial inflow to stimulus frequency was 0.17 ml min-1g-1 Hz-1 and that of secretion to stimulus frequency was 0.016 ml min-1g-1 Hz-1. 2. The secretory response to low and moderate levels of parasympathetic nerve stimulation (below 8 Hz) was not affected by a reduction or cessation in arterial inflow whereas the response to high level parasympathetic nerve stimulation (above 8 Hz) was significantly alleviated if blood flow to the gland was maintained (via controlled vascular perfusion) at a level less than that of the resting arterial inflow. However, when the gland was already secreting near maximally (stimulated at 8 Hz), sudden cessation of blood flow for a short period of time (0.5-2 min) had no effect on the salivary flow. 3. Continuous stimulation of the cervical sympathetic nerve for 1-2 min at supramaximal voltage (20 V) and pulse duration (1 ms) decreased arterial inflow and this was accompanied by scanty salivary secretion. The vascular response persisted during the period of stimulation. The secretory response was 15 s late in onset and might continue for 1 min after stimulation. The frequency for initiating the responses was 1-4 Hz. Maximal responses occurred at 16-32 Hz. The response coefficient of arterial inflow to stimulus frequency was -0.04 ml min-1g-1Hz-1 and that of salivary secretion to stimulus frequency was 0.001 ml min-1g-1Hz-1. 4. The secretory response to sympathetic nerve stimulation at different frequencies in glands with blood flow maintained at resting rate (via controlled vascular perfusion) resembled that in glands with spontaneous blood flow. 5. Sympathetic nerve stimulation was found to retard salivary secretion caused by parasympathetic stimulation, irrespective of whether the gland received spontaneous arterial inflow or controlled vascular perfusion at a resting flow rate. 6. The results suggest that the salivary secretion to stimulation of parasympathetic nerve is independent of blood flow over a wide range of stimulus frequencies; however, the response to high frequency stimulation of the parasympathetic nerve may be affected by fluctuations in blood flow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2100313 TI - Interval dependence of force and twitch duration in rat heart explained by Ca2+ pump inactivation in sarcoplasmic reticulum. AB - 1. The influence of the interstimulus interval on twitch duration was analysed in isolated heart muscle of the rat. When the muscle was in the steady state at interstimulus intervals at 5 s a test interval was interposed and varied. Duration of twitch and action potential, sarcomere length and peak force of the test beats were measured. 2. Twitch force and duration increased when the test interval was increased from 0.4 to 10 s. This effect was abolished by inhibitors of sarcoplasmic reticulum function (ryanodine, caffeine, Sr2+). Hence, the interval dependence is controlled by the sarcoplasmic reticulum. 3. Post extrasystolic potentiation, variation of [Ca2+]o and [Na+]o and blocking of iCa with nifedipine and Mn2+ led to large variations in force, reflecting variations in the amount of Ca2+ released from the sarcoplasmic reticulum. The effect on twitch duration was small, indicating that twitch duration was rather insensitive to the amount of released Ca2+, and not controlled by iCa and Na(+)-Ca2+ exchange. 4. Action potential duration was much shorter than twitch duration and, depending on the intervention, changes were in the same or in opposite direction. Hence, the action potential did not determine twitch duration. 5. Small variations in sarcomere length amongst test contractions were observed, but these variations could not account for the effects of the test interval. 6. It is proposed that the Ca2+ pump in the sarcoplasmic reticulum is activated during each contraction and inactivates slowly. Thus, after a short interval the pump is still activated and rapidly sequesters much of the released Ca2+ leading to a small twitch and rapid relaxation. This mechanism ensures proper relaxation and diastolic filling of the ventricle. The biochemical basis and implications of the hypothesis are discussed. PMID- 2100315 TI - 4-Aminopyridine causes a voltage-dependent block of the transient outward K+ current in rat melanotrophs. AB - 1. Whole-cell voltage-clamp recordings were made from acutely dissociated melanotrophs obtained from adult rats. 2. In the presence of external Na+ and Ca2+ channel blockers and 20 mM-tetraethylammonium (TEA) depolarizations to -40 mV or more evoked a fast-activating fast-inactivating outward K+ current (IK(f)). Double-pulse experiments showed that steady-state half-inactivation occurred near -37 mV; half-maximal activation of IK(f) occurred at -15 mV. Recovery from inactivation in most cells fitted a single exponential with a time constant of 40 50 ms. 3. When applied either internally or externally, 1-2.5 mM-4-aminopyridine (4-AP) substantially reduced IK(f) but the degree of block was affected by the intensity, duration and frequency of depolarizing commands. 4. Analysis of the steady-state voltage dependence of the block by 4-AP showed that half-maximal blocking occurred at approximately -31 mV. This implied that 4-AP binds to the resting state of the IK(f) channel. 5. Studies of the time dependence for the blocking or unblocking of IK(f) showed that both processes were exponential with mean time constants of 1942 ms (at -70 mV) and 726 ms (at 20 mV), respectively. Recovery from inactivation was apparently unaffected by 4-AP. 6. A four-state sequential model in which 4-AP reversibly binds to the resting state of the channel replicates the frequency dependence of the 4-AP blockade. PMID- 2100316 TI - Is increased metabolism in rats in the cold mediated by the thyroid? AB - 1. In the rat variation of metabolic heat production is the principal effector of thermoregulation. There is a continuous relationship between ambient temperature and metabolic rat over the whole range of tolerable environmental temperature. The mechanism that controls metabolic rate is unknown; this paper reports an attempt to test whether thyroid hormones provide the controlling pathway. 2. First, the changes in metabolic rate and in the plasma concentrations of thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) were measured in rats living in a controlled environment, first at 23 degrees C and then at 6 degrees C. Metabolic rate increased from approximately 290 to 470 kJ day-1 when the temperature was lowered, a factor of ca 1.6, and the diurnal rhythm disappeared. The concentration of TSH increased from approximately 320 to 450 ng ml-1 (with loss of diurnal rhythm) and of T3 from ca 0.7 to 1.0 nmol l-1, a factor of ca 1.4 in each case. T4 concentration did not change. 3. Next, a dose schedule of T3 was found that, when injected I.V. via indwelling jugular cannulae in the same rats in an environment at 23 degrees C, maintained an increase in T3 concentration rather greater than had been found at 6 degrees C. 4. This dose of T3, given to the same rats at 23 degrees C, did not affect metabolic rate (or its diurnal pattern). 5. It is therefore unlikely that the increase in T3 concentration evoked the increase in metabolic rate when ambient temperature was changed from 23 to 6 degrees C; and therefore that the thyroid controls variation of metabolic rate in 'everyday' thermoregulation in the rat. PMID- 2100317 TI - Responses of bone and joint blood vessels in cats and rabbits to electrical stimulation of nerves supplying the knee. AB - 1. Experiments were performed to assess the extent to which knee joint blood flow in cats and rabbits is affected by electrical stimulation of the nerve supply to the knee. 2. Absolute changes in blood flow were measured using the radiolabelled microsphere (approximately 15 microns) technique whilst relative changes in blood flow were assessed using laser Doppler flowmetry. 3. Despite deep general anaesthesia, sympathetic nerve fibres innervating cat knee joint blood vessels showed marked 'tone'. 4. Blood flow to the joint capsule (synovium and overlying fibrous and areolar tissues) was substantially reduced (by approximately 90% in the cat and approximately 45% in the rabbit) during electrical stimulation of the articular nerve supply. 5. The percentage change in the laser Doppler flowmeter signal did not differ significantly from the percentage change in blood flow measured by microsphere technique. 6. Blood vessels in the cancellous bone of the distal femur (condyles) and proximal tibia (plateau) appear to be innervated by vasoconstrictor fibres which reach their effectors via the articular nerves. However, the cortical bone and red marrow of the diaphysis of the femur do not receive such innervation. 7. The potency of the vasoconstrictor influences acting on joint blood vessels could be of relevance in the pathogenesis of inflammatory joint diseases. PMID- 2100318 TI - The neurotoxicology and pathology of organomercury, organolead, and organotin. AB - The toxicities of many metals, such as mercury and lead, are known to man since the dawn of civilization. Organic compounds of some heavy metals are known to have a particular toxic impact on the central nervous system. Organomercury, particularly alkyl-mercuric compounds (e.g. methylmercury), has a selective effect on the granule cells of the cerebellum, the nerve cells of the calcarine cortex, and the sensory neurons in the dorsal root ganglia. The well known Minamata Bay disease is the result of a massive epidemic episode of human exposure to alkylmercury contaminated food sources. Mental retardation and other developmental defects are also known to be a consequence of exposure to this toxic metal. Organic lead compounds have been employed as gasoline additives and in other industrial purposes. Unlike its inorganic counterpart, organolead compounds have a more prominent impact on the central nervous system. Pathological changes of the brain stem neurons have been described. Organotin compounds have been used in plastic industries and as agricultural chemicals. Both trimethyl and triethyl tin compounds are found to be extremely neurotoxic. Despite the similarity of their chemical structures, trimethyl and triethyl tins have a diversely different toxic property and effects. While triethyl tin is myelinotoxic, producing edematous and vacuolar changes in the central myelin, trimethyl tin is neurotoxic, producing prominent toxic changes in the neurons of the limbic system (hippocampus, entorhinal cortex, etc.). The factors which determine the specificity and selectivity of the neurotoxic impacts by various organometals are still unknown. In view that most of the organometals are still widely employed by many countries for industrial and for agricultural purposes, caution must be made for their proper handling and disposure to avoid undesirable exposures to workers and environmental contamination of water sources and food chain for the common public. Since organometals are difficult to eliminate from the central nervous system, injuries usually lead to permanent neurological deficits, such tragedies are frequently long lasting and create not only a medical problem, but also a social economical problem for the society. PMID- 2100319 TI - The carcinogenic potential of cadmium, arsenic, and selenium and the associated public health and regulatory implications. PMID- 2100320 TI - Practical considerations for the development and risk assessment of pesticides. PMID- 2100321 TI - [Hyperparathyroidism in patients with respiratory decompensation]. AB - Eighteen patients aged between 55 and 65 and affected by respiratory insufficient were included in the study. Serum levels of PTH, total calcium, Ca++ and phosphorus were measured. Special attention was focused on PTH concentrations with in some case provedo to be above normal. Two hypotheses of pathogenesis are put forward. The first suggests that reduced Ca++ levels are responsible for anomalous PTH serum concentrations, whereas the second suggests that this role may be played by hypoxia. The latter would indirectly or directly affect parathyroids, either increasing PTH hyperincretion or slowing down the metabolism of the hormone by kidneys and liver which are in turn negatively affected by low blood oxygen tension. PMID- 2100322 TI - [Techniques of celiac plexus block and clinical results]. AB - Coeliac plexus neurolesion techniques for pain due to upper abdominal cancer (pancreas cancer above all), have changed during the years. In this paper we report the results of coeliac plexus alcohol neurolysis for cancer of pancreas and of other abdominal organs achieved with the different techniques. It appears that precrural techniques provide very favorable results but they require the use of CT scan. Retrocrural techniques, while giving good results, can be performed under fluoroscopic control. PMID- 2100323 TI - [Stellate ganglion block in the treatment of ischemic syndrome in an upper limb due to accidental intra-arterial injection of pharmacologic substances or narcotics]. AB - The paper describes five cases of accidental intraarterial injection of pharmacological drugs (diazepam or thiopentone) or dope (heroin) in an upper limb. Following a review of the physiopathological mechanisms which led to ischemic damage, the Authors outline a protocol of continuous pharmacological sympathicolysis in the affected limb, using repeated anesthetic blocks of the homolateral stellate ganglion. PMID- 2100324 TI - [Possible effects of pharmacologic prophylaxis for Mendelson's syndrome on newborns]. AB - Forty-eight newborn infants whose mothers underwent both elective and urgent caesarean section were studied. Mothers were randomly assigned to one of the treatment groups for the prophylaxis of Aspiration Pneumonitis: group A was treated with ranitidine, 50 mg i.v.; group B with ranitidine, 50 mg, and metoclopramide, 10 mg i.v.; group C no medication. Neonatal assessment included Apgar score and various haematological laboratory tests: haemogasanalysis, glycemia, electrolites, hematocrit, hemoglobin, bilirubinemia, SGOT, SGPT. Nor clinical or statistic differences were noted among the three infant groups. PMID- 2100325 TI - [Continuous infusion peridural analgesia in labor]. AB - A technique of continuous infusion epidural anesthesia was used during labour in 933 patients divided into three groups according to age: Group A (14-18 years old), Group B (19-35 years old) and Group C (greater than 35 years old). Infusion was carried out using the following system: a PVC pressurized bag containing 0.3% marcain connected to 2 flow regulators which ensured a flow of 6 ml/h. During the dilatation phase, 85% of patients received sufficient analgesia, whereas 15% required extra boluses. During the expulsive phase 80% of patients received adequate analgesia of the perineal plane, 12% received an extra bolus of marcain 0.3% and local anesthesia was performed in 8% to allow infiltration. Instruments were required in 5.6% of patients in Group A, 11.3% in Group B and 7.4% in Group C. The incidence of Caesarian section was 5.6% in Group A, 9% in Group B and 14.8% in Group C. No maternal complication was observed. Epidural anesthesia via continuous infusion was therefore shown to be an efficacious and safe method for ensuring analgesia during labour. PMID- 2100326 TI - [The clinical use of levosulpiride in retinal fluorangiography]. AB - The value of administering 25 mg of levosulpiride per os approximately one hour before the sodium fluorescein bolus used in fluorangiography is assessed in order to avoid to the onset of nausea and/or vomiting during and after the test. The study was performed in 35 patients. No nausea and/or vomiting was observed in over 90% of cases treated. PMID- 2100327 TI - [Experience with a semirigid fiberoptic laryngoscopy]. PMID- 2100328 TI - [Neuroleptic malignant syndrome. A case report]. AB - A psychotic received neuroleptics and lithium salts for a few days, developing a classic clinical presentation of a neuroleptic malignant syndrome. Treatment in our ICU was started with dantrolene sodium and bromocriptine p.o., associated with artificial cooling of the body and cardiac, respiratory and metabolic measures. In this way we were able to normalize the clinical conditions of the patients. The clinical description of this case allows a general review of the literature on this "rare" syndrome, starting from the anaesthesiologist point of view. PMID- 2100329 TI - [Hydrothorax as a complication of subclavian vein catheterization. Pathogenetic mechanism and description of a clinical case]. AB - We report a case of possible detouring and malfunctioning of the left subclavian catheter in the homolateral internal mammary vein or of perforation form its tip of the wall of the left innominate vein. The tip of the catheter was rigid and sharp, may be the contractions of the heart or turbulent flow impinged it against the vein wall and have enhanced the perforation. The result was a hydrothorax that allowed a severe cardiac simile tamponed syndrome. The pathophysiology was also discussed. PMID- 2100330 TI - [Poisoning with shoe dye. A clinical case]. AB - The paper reports the case of a young male which was severely poisoned by anilyne shoe black. After a few hours, he was in a semicomatose state, accompanied by "very dark" arterial blood gases with oxygen tension in excess of 100 mmHg. Following the administration of intravenous methylene blue (2 mg/kg), methemoglobin was reduced to hemoglobin and the level of consciousness immediately improved. PMID- 2100331 TI - The dynamic nurse-patient relationship. Function, process, and principles. 1960. PMID- 2100332 TI - [Ether lipids--synthesis and application in tumor therapy]. PMID- 2100333 TI - Cellular mechanisms in excitation-contraction coupling. PMID- 2100334 TI - [Red blood cells as carrier systems for drugs]. PMID- 2100335 TI - Convenient synthesis of 1-phenyl-1,2-propanediamines. Preliminary pharmacological results. AB - A novel synthesis of (1R,2S)- and (1S,2S)-1-phenyl-1,2-propanediamines by highly regioselective and stereo-specific opening of chiral aziridines is reported. This method permits the synthesis of optically pure diastereomers. A hypothermic effect is observed after intracerebroventricular injection in rats. PMID- 2100336 TI - [Development of press-coated tablets with controlled-release effect with a base of poly-d(-)-3-hydroxybutyric acid]. AB - A new drug delivery system with controlled-release effect based on press-coated tablets using poly-D(-)-3-hydroxybutyric acid (Poly-HB) is presented. Model investigations show that the coating of a drug containing core with an indifferent matrix consisting of Poly-HB, a channeling agent (sodium chloride, potassium nitrate or lactose) and the initial dose of the drug leads to a zero order release kinetics. The system is applicable for oral and parenteral dosage of various drugs. PMID- 2100337 TI - An improved topical formulation for urea. AB - The solubility of urea in different polar solvents was studied by means of determination of their dielectric constants. The most appropriate solvents turned out to be water and a water/propylene glycol (1:1 in volume) mixture. The best solvents were then used in the study of different semisolid vehicles for topical use (cetylic excipient, Beeler's base and Carbopol gel), which show different physicochemical characteristics. The final formulation contained a 40% (w/w) concentration in urea, since this value is most often used in Dermatology and, at the same time, it is the most problematic from a technological point of view. The stability of the different preparations was investigated by conductimetric and rheological determinations. The results are discussed in terms of both the solubility and stability of the active principles and the organoleptic and rheological characteristics of the final preparations. PMID- 2100338 TI - The influence of ethanol on the distribution of amitriptyline and nortriptyline in rats. AB - The influence of ethanol in single and multiple doses on concentration-time profile of amitriptyline (1) and nortriptyline (2) in rat serum, brain, heart, and liver was studied. AUC0-6 values were calculated and statistically compared as well as cmax values in serum and tissues. Ethanol inhibited N-demethylation of 1 and therefore 2 has not been detected in biological material. AUC0-6 and cmax values were less than in control group. All AUC0-6 and cmax values for 1 in ethanol treated groups of rats were statistically significant compared with the control group. PMID- 2100339 TI - [Judicial protection of monoclonal antibodies]. AB - Possibilities of an application for a patent abroad in foreign countries are discussed concerning monoclonal antibodies which will have good chances as diagnostics in future. To obtain firmly patent rights, prerequisites as sufficient explanation of the invention, novelty and inventive accomplishment as well as a survey of the intensity of application are given. PMID- 2100340 TI - [An attempted founding of the "Pharmazeutischen Gesellschaft" in the year 1884/85]. AB - The attempt on the foundation of the Pharmaceutical Society in 1884 and its final failure in 1885 are described. In 1884/85 the conditions of the foundation of the Pharmaceutical Society were very inconvenient. In 1890 the circumstances had changed. Better economical conditions of the pharmacies, the beginning of an effective pharmaceutical industry and the diplomatic dexterity of Hermann Thoms facilitated the foundation of a Pharmaceutical Society with scientific aims. PMID- 2100341 TI - [Determination of prednisolone in ointments]. AB - A method for the quantitative determination of prednisolone in ointment preparations is described. It uses TLC and UV spectrophotometry in combination. Solutions and ointments are chromatographed using silica gel GF 254 and various solvent systems, the layers containing the active ingredient are eluted and the substance determined at 240 nm. PMID- 2100342 TI - Synthesis and antimicrobial activity of aromatic dicarboxaldehydes. PMID- 2100343 TI - Some 1,3,4-oxadiazoline derivatives prepared by starting from benzylic acid hydrazide aryl hydrazones and their antimicrobial evaluation. PMID- 2100344 TI - Preparation and preliminary evaluation of sustained-release acetylsalicylic acid tablets. PMID- 2100345 TI - [The effect of purine nucleosides on the 3H-adenosine uptake in cultured endothelial cells]. PMID- 2100346 TI - Individual differences in behaviorally evoked cardiovascular response: temporal stability and hemodynamic patterning. AB - This study evaluates the reproducibility of individual differences in behaviorally evoked cardiovascular reactivity among 39 young adult males. Presented also are initial data describing idiosyncratic patterns of hemodynamic adjustment that may underlie pressor responses to laboratory stressors. Subjects were administered three experimental stressors (mental arithmetic, mirror tracing, and bicycle exercise) on two occasions, four weeks apart. Heart rate, blood pressure, and impedance-derived measurements of cardiac pre-ejection period, stroke index, cardiac index, and total peripheral resistance were obtained during baseline and task periods at each session. To index task-induced "reactivity," residualized (baseline-adjusted) change scores were calculated for all variables; percentage change from baseline was also calculated for impedance derived hemodynamic measurements. Test-retest (inter-session) correlations were significant for nearly all baseline, task, and change-score measurements. The few exceptions included diastolic blood pressure changes during mirror tracing and bicycle exercise and changes in stroke index and peripheral resistance during mental arithmetic. Although virtually all baseline and task correlations exceeded .60, reactivity indices yielded consistently lower retest correlations (significant r's = .35-.78; median r = .49). In subsequent analyses, subsets of individuals were identified whose reactions to mental arithmetic at the first laboratory session reflected changes in either cardiac output (CI reactors, n = 9) or total peripheral resistance (TPR reactors, n = 6), or a combination of cardiac and vascular influences (Mixed reactors, n = 8). This typology of hemodynamic response: (a) was corroborated by corresponding group differences in heart rate, pre-ejection period, and stroke index; (b) was reproducible on retesting; and (c) showed some generalization to the mirror tracing task, though not to bicycle exercise. PMID- 2100347 TI - Diurnal variations of ECG parameters during 23-hour monitoring in cardiac patients with ventricular arrhythmias or ischemic episodes. AB - ECG and physical activity (recorded with motion detectors) were continuously monitored during 23 hours in 31 male cardiac patients (81% with myocardial infarction). According to the occurrence of ventricular arrhythmias (VA) or ischemic episodes (IE), each patient was grouped in one of three diagnostic categories: neither VA nor IE, VA with or without IE, and IE only. Analysis of the ECG parameters was done beat-by-beat and averaged on a 1-min basis. Results were derived from the 2-hour means between 2 p.m. and 12 p.m. MANOVA revealed significant group differences for heart rate variability (greater for the group with VA), R-wave amplitude (higher for the group with IE), and P-wave amplitude (higher for the group with VA). Significant time effects were observed for all variables except QRS- and P-wave durations. As may be expected, physical activity and heart rate were lower at night. Heart rate variability, PQ-interval, PR segment, QT-interval, ST-segment, and T-wave duration increased during the night. R-wave amplitude also increased but the relative P- and T-wave amplitudes decreased. The corrected QT-interval, QTc, was shorter at night and the ST segment, J + 60-point, S-wave, and J-point amplitudes were less negative. Group X Time interactions were observed for T-wave amplitude. For this amplitude, the decrease during the night was prominent only for the VA group. The results of this study suggest that the three diagnostic groups can be differentiated by diverse ECG parameters. PMID- 2100348 TI - Brain generators implicated in the processing of auditory stimulus deviance: a topographic event-related potential study. AB - The neurophysiological mechanisms underlying mismatch negativity (MMN) can be inferred from an examination of some of the brain generators involved in the process of this event-related potential (ERP) component. ERPs were recorded in two studies in which the subjects were involved in a selective dichotic listening task. Subjects were required to silently count rare stimuli deviating in pitch from a sequence of standard stimuli in one ear, while ignoring all the stimuli (standards and deviants) delivered randomly to the other ear. The results showed that, in all cases, the negative wave elicited by the deviant stimuli showed the highest amplitudes over the right hemiscalp irrespective of the ear of stimulation or the direction of attention. Scalp radial current density analysis showed that this asymmetric potential distribution could be attributed to the sum of activities of two sets of neural generators: one temporal, located in the vicinity of the primary auditory cortex, predominantly activated in the hemisphere contralateral to the ear of stimulation, and the other frontal, involving mainly the right hemisphere. The results are discussed in light of Naatanen's model: we suggest the dissociation of two functional processes on the basis of activity of distinct brain areas: a sensory memory mechanism related to the temporal generators, and an automatic attention-switching process related to the frontal generators. PMID- 2100349 TI - Cardiopulmonary adjustments during operant heart rate control. AB - Twenty-three healthy men and women participated in a 5-session experiment in which they attempted to increase and decrease their heart rate with the assistance of visual analogue biofeedback. As a group subjects did successfully raise and lower heart rate from resting baseline. These changes in heart rate were closely paralleled by changes in V, a measure of cardiac vagal tone. Heart rate slowing was associated with increases in V, and heart rate speeding was associated with decreases in V. Respiration rate and amplitude did not differ significantly between heart rate slowing and speeding trials, and covariance analysis indicated that respiratory changes did not account for the heart rate or V effects. The weighted coherence between respiration and heart rate showed that cardiopulmonary coupling increased during heart rate slowing and decreased during heart rate speeding. Individual differences in cardiac vagal tone and cardiopulmonary coupling were unrelated to heart rate speeding and slowing performance. PMID- 2100350 TI - Electrodermal responsivity in young hypotensive and hypertensive men. AB - Electrodermal responses were recorded during the presentation of 16 moderately intense (1000 Hz, 90dB) tones in three groups of young men: borderline hypertensives (138/79 mmHg), normotensives (112/65 mmHg), and hypotensives (104/63 mmHg). Electrodermal response habituation was measured as a decline in response over trials, number of trials to a response criterion of three successive nonresponses, and number of inversions of response amplitude (larger responses following smaller responses) in the stimulus sequence. Habituation was fastest in hypotensives. Nonspecific electrodermal responses at rest and during tone presentations were most frequent in borderline hypertensives, least frequent in the hypotensive group, with the normotensive group falling in between. There were no significant differences in electrodermal level. The rapid habituation rate in hypotensives is discussed in terms of cursory information processing associated with impulsive behaviour. The higher nonspecific electrodermal activity in borderline hypertensives is interpreted to indicate increased sympathetic nervous system activity. PMID- 2100351 TI - Hemodynamics of blood pressure responses during active and passive coping. AB - This laboratory study was designed to address a number of interrelated issues regarding cardiovascular reactivity to psychological stress. One objective was to extend the previous research comparing cardiovascular responses during active versus passive coping, by comparing responses to two task conditions designed to be similar in all ways except the opportunity to make a response influencing the task's outcome. A second objective was to compare responses to two different passive film tasks, which differed in outcome uncertainty and the degree of vicarious active coping achieved through identification with the role portrayed by the actors. A third objective was to evaluate whether individuals are predisposed to exhibit a particular hemodynamic pattern underlying their blood pressure adjustments, independently of the task demands imposed. Ninety healthy young adult male subjects were tested in pairs on a series of tasks that included a competitive reaction-time task, an active as well as a passive phase of a team reaction-time task, and passive viewing of two film segments. The tasks demanding active coping responses tended to raise blood pressure due primarily to an increase in cardiac output, while vascular resistance fell. During passive coping demands cardiac output increased to a lesser extent, but vascular resistance also tended to increase, thereby raising blood pressure by their synergistic effects. However, these patterns were not typical of all participating subjects. On the basis of their cardiac output and vascular resistance responses to the competitive reaction-time task, one third of the subjects were categorized as being high myocardial reactors (n = 30) and another third high vascular reactors (n = 31). Post-hoc analyses of responses to the other tasks, based on these categorizations, indicated that the hemodynamic basis of reactivity is an individual characteristic only partially modified by coping demands. The active/passive coping dimension is discussed both conceptually and in relation to the role of stress in the etiology of hypertension. PMID- 2100352 TI - Event-related potentials in a visual discrimination task: negative waves related to detection and attention. AB - Event-related potential effects of deviant stimuli were investigated in a visual discrimination task. The stimuli (two angles within a frame) were either frequent (Standard) or one of two types of infrequent deviant (Deviant 1 or Deviant 2) stimuli. In comparison to the Standard stimuli, for Deviant 1 the two angles differed in their orientation, whereas for Deviant 2 the angles were identical but the frame was thicker. In Condition 1 the subjects counted the number of Deviant 1 stimuli. Of the 13 subjects, 12 did not detect the fact that some of the frames were thicker in this condition (i.e., for the Deviant 2 stimuli in Condition 2). The task in Condition 2 was the same (i.e., the target was Deviant 1), but the subjects were instructed about the thicker frame of Deviant 2 stimuli. In Condition 3, Deviant 2 stimuli became the targets. In comparison to the Standard, Deviant 1 elicited two posterior negative waves in the 120-180 and 240-300 ms latency ranges respectively. In addition, when Deviant 1 was the target stimulus (Conditions 1 and 2), this stimulus elicited the N2 and the P300 as well. In contrast, the irrelevant Deviant 2 elicited no such waves. In the target position (Condition 3), Deviant 2 elicited the second posterior negativity, the N2 and the late positivity. The earlier negativity is considered to be a correlate of processes connected to the automatic detection of the deviant features, whereas the later negativity is considered to be related to attentive processes, i.e., this wave is considered to be a member of the family of processing negativities. PMID- 2100354 TI - Facial coloration and temperature responses in blushing. AB - Little work on the psychophysiology of blushing has been done since Darwin's 1872 observations. Facial vascular and temperature changes have been largely ignored in psychophysiology. We had 16 female and 16 male undergraduate volunteers watch a videotape intended to produce blushing (the individual's singing recorded the previous day), and a videotape not intended to produce blushing, but elicit physiological responses for comparison (a segment from Hitchcock's movie Psycho). Four people were present as a subject watched these video segments. Cheek and ear coloration, measured photoplethysmographically, cheek temperature, and finger skin conductance responses were significantly greater during stimulation intended to elicit blushing than during comparison stimulation. Gender interacted statistically with kind of stimulation only in cheek temperature. Only video segments of the subject's face that coincided with maximal cheek coloration during stimulation intended to produce blushing were judged reliably as blushing, and then more often in females than in males. PMID- 2100353 TI - Sleep stage physiology, mood, and vigilance responses to total sleep deprivation in healthy 80-year-olds and 20-year-olds. AB - Little is known about sleep and the effects of total sleep loss in the 'old old' (i.e., 80-year-olds). We investigated sleep, mood, and performance responses to acute sleep deprivation in healthy 80-year-olds (n = 10) and 20-year-olds (n = 14). The protocol consisted of three nights of baseline sleep, one night of total sleep deprivation, and two nights of recovery sleep. Mood and vigilance were tested using visual analog scales and a Mackworth clock procedure in the morning and evening of each study day. Daytime sleepiness was measured by five naps on the days following the third and sixth nights. Old subjects had lower sleep efficiency and less delta sleep than young subjects. However, sleep continuity and delta sleep were enhanced in both groups on the first recovery night, indicating that sleep changes in old subjects are at least partially reversible by this procedure. Surprisingly, young subjects had shorter daytime sleep latencies than the old, suggesting a greater unmet sleep need in the former group. Mood and performance were disturbed by sleep loss in both groups, but to a greater extent among the young. This suggests that acute total sleep loss is a more disruptive procedure for the young than for the old. PMID- 2100355 TI - Acute emotional and cardiovascular effects of stressful mental work during aerobic exercise. AB - The acute effects of engaging in challenging mental work during a single session of aerobic exercise were examined on measures of subjective mood and cardiovascular function. Fifty-seven female subjects were randomly assigned to participate in either a 10-min aerobic exercise condition or a no-exercise control condition. Half of the subjects in each group performed digits backward problems during this time period, and no mental stressors were presented to the other subjects. The results indicated that the exercise and mental stress conditions had additive effects on subjective anxiety levels and on cardiovascular responses during exercise. Both exercise and mental stress increased heart rate. In addition, exercise had anti-anxiety and vasodilative effects, but both of these influences were attenuated by opposing main effects for mental stress exposure. No effects were found for exercise on measures of cardiovascular reactivity to a later digits backward stressor. The results are consistent with previous research in suggesting that exposure to mental stressors during aerobic exercise provides no acute psychological benefits but attenuates some of the mood improvements and vasodilative effects of the exercise activity. PMID- 2100356 TI - A comparison of three quantification methods for estimation of respiratory sinus arrhythmia. AB - The empirical literature has shown that respiratory sinus arrhythmia is a sensitive noninvasive index of parasympathetic cardiac control. Nevertheless there has been no general agreement among investigators as to the most preferable quantification technique for assessing respiratory sinus arrhythmia, although there has been much speculation that specific estimation techniques are more or less reflective of vagal processes and could be more or less contaminated by other influences upon heart period variability unrelated to respiration. This study compared three quantification procedures for estimating respiratory sinus arrhythmia (RSA): (1) a spectral analytic technique, (2) a complex detrending approach removing periodic and aperiodic cardiac variations unrelated to respiration, and (3) a time-domain, peak-valley procedure employing inspiratory and expiratory periods as windows for determining range of cardiac-interval fluctuations associated with respiratory phase. Measures derived from these techniques were intra- and interindividually compared using three different samples of male subjects, including students, adult normotensives, and adult hypertensives. All interindividual correlations between measures yielded coefficients above .92 and the mean within-subject correlation across 42 individuals was .96, thus indicating a marked degree of comparability between measures. Additionally, given that much evidence indicates lawful within individual relations between RSA amplitude and respiratory parameters, we employed respiratory period as an external criterion and compared intraindividual correlations between this variable and (2) and (3); results showed that (3) was significantly more highly associated with respiration than was (2), although the mean r's for the two measures did not diverge greatly (.91 vs. .84). Finally, inspection of the data and further regression analyses did not suggest that any of the RSA estimates were differentially contaminated by other components of cardiac variability. Our findings suggest that the three techniques are almost equivalent as indices of cardiac vagal tone and would appear to ease concerns about the inferiority of any of the procedures. Choice of a quantification procedure should therefore be tailored to the specific empirical needs of an investigation. The advantages and disadvantages of each method are discussed. PMID- 2100357 TI - Chromosomal evolution and speciation in primates. PMID- 2100358 TI - Measuring quality of life in medicine. AB - Quality of life has emerged as an important outcome in evaluating medical care. With an increasing number of patients with chronic disease, it is necessary not only to assess an intervention regarding its ability to effect cures, but also regarding its ability to improve the quality of life. Self-administered patient questionnaires provide a reliable and valid means of assessing how patients respond to therapy. Basically, there are two types: specific and general questionnaires. Whereas general questionnaires give a comprehensive evaluation of the quality of life summarized in a global score, specific questionnaires are focused on a particular problem or patient group. Benefits and disadvantages of generic compared with specific questionnaires are discussed. PMID- 2100359 TI - The Nottingham Health Profile--a measure of health-related quality of life. AB - Assessment of quality of life has attracted increasing interest in recent years. A standardized way of evaluating quality of life is by using questionnaires. One such, the Nottingham Health Profile (NHP), measures health-related quality of life within the sections of energy, sleep, emotions, pain, mobility and social isolation as well as the frequency of health-related problems pertaining to paid employment, housework, hobbies, family life, social life, sex life and holidays. The NHP is well-documented with regard to reliability and validity, and is useful in describing the impact of chronic disease. The NHP is, moreover, a useful evaluative tool in patients with more pronounced disability. PMID- 2100360 TI - The SSA-profile, an instrument for assessment of subjective symptoms among hypertensives. AB - The SSA-profile is a specific, self-administered questionnaire for measurement of subjective symptoms in untreated and treated hypertensives. Forty-two of the most frequently occurring symptoms among untreated and treated hypertensives have been included. Based on factor analysis, 25 of the items combine into dimensions covering the areas Emotional distress, Gastro-intestinal symptoms, Peripheral vascular symptoms, Cardiac symptoms, Sex life and Dizziness. The reliability and circulatory of the questionnaire have been established. For improved sensitivity in detecting subjective symptoms and comparability of results obtained in different studies the use of the SSA-profile provide valuable information. The questionnaire has been shown capable of describing subjective symptoms among untreated hypertensives. Currently, the questionnaire is being used in evaluating subjective symptoms among patients treated with different classes of antihypertensive agents. PMID- 2100361 TI - Questionnaire for the Assessment of Symptoms and Psychological Effects in Cardiovascular Therapy (the ASPECT Scale). AB - This brief review summarizes the background and principles for the development of a new psychometric instrument (Assessment of Symptoms and Psychological Effects in Cardiovascular Therapy--ASPECT Scale). The test consists of two parts, one for assessment of three aspects of global well-being (hedonic tone, relaxation, and activity) and one for evaluation of 34 commonly experienced symptomatic side effects of cardiovascular drugs. All items are assessed by visual-analogue scales, and six clusters of symptoms have been identified: cardiac symptoms, central nervous system or cognitive symptoms, fatigue, local/cutaneous symptoms, sleeping disturbances, and other symptoms. PMID- 2100362 TI - "The Goteborg quality of life instrument"--an assessment of well-being and symptoms among men born 1913 and 1923. Methods and validity. AB - "The Goteborg quality of life instrument" (GQL-instrument) has been used to assess the quality of life of men born in 1913 and 1923. On a population basis, it was possible to show that the well-being variables were stable over time and that excellent well-being showed a great variation. A high level of well-being was common in variables such as family and housing but more uncommon in variables such as fitness, vision, hearing and memory. Symptoms were often significantly related to biomedical variables such as body mass index, blood pressure, lung function, blood lipids, fasting blood sugar and fasting insulin. The GQL instrument seems to provide a reliable and stable assessment of well-being and symptoms and is useful both as a descriptive tool, and as a help in evaluating treatment, and it also has predictive power. PMID- 2100363 TI - Goteborg quality of life study of men born in 1913 and 1923--age, sex, job satisfaction and cardiovascular diseases. AB - To see whether well-being and symptoms are affected by age, job satisfaction, and cardiovascular diseases a quality of life assessment of men born in 1913 and 1923 and living in Goteborg was performed. Age influenced both well-being and symptoms in different ways. Many well-being variables declined and many symptoms decreased with age. Symptoms were strongly related to both global health and job satisfaction--more symptoms were found in participants with low global health or low job satisfaction. Participants with cardiovascular disease and diabetes mellitus showed considerable variation in their quality of life. Hypertensive and diabetic patients showed only small deviations in the well-being and symptom profile. Congestive heart failure patients generally had a low quality of life. It was not possible to decide if the lack of well-being was caused by the diseased state, the treatment, or the patients' awareness of having a specific disease. PMID- 2100364 TI - Differences in perceived symptoms/quality of life in untreated hypertensive and normotensive men. AB - To evaluate adverse reactions in the treatment of hypertension correctly, it is important to know the symptom profile of hypertensives per se. In the present study, a random sample of 60-year-old men, untreated for hypertension, was studied. The concept of the quality of life has largely been based on data obtained from the self-recording of subjective symptoms. Subjective symptoms were recorded by means of a self-administered questionnaire, "The Goteborg Quality of Life Instrument", which includes 30 items. Nine of the symptoms were found to be correlated to blood pressure. When the effect of confounding factors, such as smoking habits and situation at work was taken into account, seven symptoms remained. Most of the symptoms that were correlated to blood pressure may be regarded as related to aetiological factors rather than caused by the blood pressure. PMID- 2100365 TI - Quality of life and hypertension. Where do we stand? New methods, new possibilities. Definition and measurement of quality of life from a medical perspective. PMID- 2100366 TI - Is quality of life affecting survival? The study of men born in 1913. AB - In this study the prognostic significance of a set of quality of life measures was tested with regard to mortality regardless of its cause, cardiovascular mortality, cancer mortality and mortality from other causes. From the population register of Gothenburg, Sweden, a sample was drawn consisting of one third of all 60-year-old men. The 945 men who met the criteria were invited to a medical examination. Information on the occurrence of 30 symptoms and 15 measures of well being was obtained by questionnaire. Mortality data were obtained through official registers, death certificates and medical records. Of the symptoms at 60, breathlessness, cough, depression, bad appetite and feeling cold, all were significantly related to mortality during 15 years of follow-up. Of the well being variables, the same was true of perceived health, physical fitness and appetite. This means that the quality of life has a strong bearing not only on the present life situation for these men but also for their future health. PMID- 2100367 TI - Life quality in non-pharmacological therapy of hypertension. AB - Measurements of life quality have recently been included in drug trials on hypertension. In literature, not one single reference was found on life quality in non-pharmacological therapy of hypertension. More or less a tacit understanding is, however, that the life quality is unchanged, or at least not impaired, during non-pharmacological therapy. Experiences from a study of 400 patients with the aim to reduce or withdraw antihypertensive drugs, at the same time as non-pharmacological methods were introduced, show the difficulties to evaluate changes of life quality in a non-pharmacological study. PMID- 2100369 TI - Defining quality of life in medicine. AB - In recent years, there has been increasing interest in incorporating the concept of "Quality of Life" in the evaluation of medical interventions. The lack of a general definition which can function as a basis for the scientific evaluation of medical treatment is, however, a problem. The definition proposed in this paper contains three main factors: Subjective well-being, Health and Welfare. "Subjective well-being" is the central component in the evaluation of Quality of Life, referring to the individual's perception of his life situation, "Health" is a subjective as well as objective evaluation of physical and mental status, while "Welfare" reflects the objective environmental factors. Thus, the evaluation of Quality of Life in medicine should ideally address these three main factors. Although the importance of any particular component may vary, subjective well being and health should always be included. PMID- 2100368 TI - Symptoms and well-being during antihypertensive treatment with thiazide diuretics. AB - Diuretic drugs seem to be well tolerated during long-term antihypertensive treatment. Although they induce severe side effects necessitating withdrawal more often than placebo, the frequency of such withdrawals seem to be equal to that induced by beta-blocker treatment. The subjective tolerability as judged by questionnaires for symptoms and well being scores seems to indicate an over-all small improvement in patient well being. The effects in this respect seem to be similar to those exerted by a selective beta-blocker. PMID- 2100370 TI - Calcium antagonists--assessment of side effects. AB - Clinically used calcium antagonists are derivatives of either verapamil (verapamil), dihydropyridines (e.g. felodipine and nifedipine), or benzothiazepines (diltiazem). The principal side effects are mostly predictable, dose-dependent, and related to their main actions: vasodilatation, negative inotropic effects and antiarrhythmic effects. All calcium antagonists have demonstrated a pronounced hypotensive effect. Conduction disturbances and bradycardia are seen more often after verapamil and diltiazem, while tachycardia, headache, ankle oedema; and flush are more frequent after felodipine and nifedipine. Another side effect is constipation, which is frequent after verapamil. Important interactions have been reported with, for instance, digoxin and beta-adrenergic blocking agents. Calcium antagonists may have favourable effects on serum lipids, and there is no indication of consistent changes in basal glucose metabolism. Uric acid is unchanged or reduced. Regarding the effects on the quality of life exerted by the different calcium antagonists, very little is known since such studies have not been performed so far. PMID- 2100371 TI - ACE-inhibitors and quality of life. AB - A review of the literature concerning quality of life aspects on ACE-inhibitors in hypertensive patients is given. In the first part of the eighties two prospective multi-center randomised trials were conducted to determine the effect of captopril in comparison to methyldopa or an unselective beta-blocker on the quality of life in patients with mild to moderate hypertension (Hill et al. and Croog et al.). Both studies revealed slight but significant positive effects on indices of quality of life in captopril treated patients compared to those who had methyldopa or an unselective beta-blocker. Later, another ACE-inhibitor, enalapril, has been compared with a selective beta-blocker (Edmonds et al. and Herrick et al.) with respect to side-effects and the quality of life. The measurements of the quality of life tended to favour enalapril, but the differences were small and the over-all tolerability of the two drugs was similar. In conclusion, comparisons with more long standing forms of antihypertensive therapy suggest a slightly more favourable effect of ACE inhibitors on the quality of life. PMID- 2100372 TI - Safety in clinical trials. AB - Safety deals with the surveillance and detection of possible threats that can arise against a patient. It might not be an obvious one, like an anaphylactic shock, but a bizarre syndrome of late onset preceded by vague signs or symptoms. To be able to conclude about a possible causal relationship between a drug and such a state with as short a delay in time as possible, the collection and analysis of adverse events during the total clinical trial program of a drug is mandatory. To ask investigators for adverse drug reactions instead is to produce an effective filter, which may help in keeping the incidence figures down in the international data sheet but which also may prove to be hazardous for the pharmaceutical industry in the long run. PMID- 2100373 TI - CD4 heterogeneity: implications for immunoregulation. PMID- 2100374 TI - Serum keratan sulfate concentration as a measure of the catabolism of cartilage proteoglycans. PMID- 2100376 TI - [The Japanese Rheumatism Association meeting. May 29-31, 1990, Osaka City. Abstracts]. PMID- 2100375 TI - Studies of a 550,000-dalton cartilage matrix glycoprotein. PMID- 2100378 TI - [Behaviour of domestic high gold alloys in telescoped crown systems]. AB - A great variety of elements and systems have been used in prosthetic dentistry for retention of removable partial dentures. The aim of this paper was to examine the possibilities for retention of telescoped crowns with parallel axial planes, made from domestic alloys, and influence of these alloys on the crowns durability. Two domestic alloys, Platinijum MPa-20 and Dentor-S, were used. Comparison between Platinijum MPa-20 and Dentor-S, and the results related to Degulor-M alloy suggested the excellent quality of domestic alloys, which recommends them as suitable materials for these purposes. PMID- 2100377 TI - [Lipoproteins and lipids of human dental plaque]. AB - Host-derived lipoproteins have not yet-been detected in human dental plaque. In this microarea only lipids and lipoprotein polysaccharides known to derive from gram-positive and gram-negative bacterias, were detected. The results of this work show that in human dental plaque there are some components analogous to human serum lipoproteins. The presence of alpha-lipoproteins was established, while beta-lipoproteins could not be detected. The studies of lipids in plaque show that plaque samples contain lipid components similar of serum free cholesterol, free fatty acids, three glycerides and cholesterol esters. Phospholipids were present in extremely small amounts. The results were discussed from the aspect of the possible origin of these lipoprotein constituents as well as from the aspect of specificity and sensitivity of procedures applied in their detection. PMID- 2100379 TI - [Possibility of use of electrophoresis on polyacrylamide gel with SDS in native human saliva]. AB - The pooled mixture of mixed and parotid samples of human saliva were investigated. The contents of proteins used in gel were lower than 300 micrograms and higher than 300 micrograms, depending on electric power and used boiled water bath. We established that the method according to Laemmli requires the mixture of buffer samples in which the content of proteins is over 300 micrograms, boiled one minute and a half in water bath. The electrophoretic process was carried out with electric power of 1 mA per sample and reproducible results were obtained. This method can also be simply used in the examination of acid proteins and basic characteristic, which are of great importance in the maintenance of normal physiological position of oral tissues. This new method can be performed without previous concentration or liophylisation of saliva. PMID- 2100380 TI - [Composite inlay]. PMID- 2100382 TI - [Supernumerary teeth of permanent dentition in children in the region of Slavonska Pozega]. PMID- 2100381 TI - [Prenatal caries prophylaxis with fluoride tablets]. AB - The attitude towards the use of fluoride tablets during pregnancy differs considerably: from absolute denying to assertion of obligate fluoride intake, even in higher doses than recommended. On the basis of our shides as well as of studies of other authors of pathohistologic, chemical and epidemiologic placental permeability of fluorides and of the influence of fluorides on the hard teeth tissues formed during the pregnancy, it can be concluded that: Fluoride application during pregnancy is a positive method since the effect of caries reduction in deciduous and permanent dentition has been confirmed; Tablets should be used from the 10the or 12the week of pregnancy; Tablets should be taken 30 minutes before the meal and an hour and a half before the intake of calcium tablets; The optimal daily dose for a pregnant woman is 1 mg of fluoride. PMID- 2100383 TI - [Intra-alveolar transplantation of tooth root]. AB - In this article the technique and results of intra-alveolar transplantation are presented. The surgical technique consisted of extrusion of the root, lying under the gingival margins, within its own socket. By this technique the root was placed into the appropriate position required for the prosthodontic restoration. PMID- 2100384 TI - [Evaluation of orthopantomographic X-ray technique in the diagnosis of impacted upper canine]. AB - In this article advantages and disadvantages of orthopantomographic x-ray technique in the diagnosis of the impacted tooth are discussed. Twenty patients were examined by orthopantomographic technique as well as by standard retroalveolar radiographs. The investigation showed that the orthopantomographic technique was not a predominant method in the diagnosis of maxillar impacted canine and that the standard retroalveolar method was more reliable. PMID- 2100385 TI - [Analysis of modified laterally positioned flap]. AB - The aim of this study was to investigate the effects of the covering of denuded root surfaces by the use of modified laterally positioned flap (MLPF) and application of supersaturated citric acid of pH 1. The following measurements were carried out: the width of attached gingiva, attachment of epithelium level, gingival recession, and plaque and gingival indices. The surface area of the exposed root was also measured. All measurements were made before MLPF and one, three, six and twelve months after the treatment. The average surface area of the gingival recession before surgery was 15.75 mm2 and one year after the treatment 4.20 mm2. This means that 73.30% of the denuded surfaces were covered. After the application of MLPF there was a statistically significant decrease of dental plaque index values and of gingival index values. The epithelium attachment was on the coronal level. Gingival recession was significantly decreased. The width of attached gingiva was statistically increased. It can be concluded that MLPF after the application of citric acid is a useful surgical procedure in the covering of denuded root surfaces. PMID- 2100386 TI - [One-year control examination of therapy of chronic apical periodontitis treated by single visit method]. AB - The results of one year control-examination of the single visit endodontic therapy of chronic apical lesions are presented. Clinical and radiographic control examinations were performed on 40 of 58 treated single and double root canal teeth from both jaws. Eighty percent of treated teeth was found to be successful. Endodontic failure was found in 15%, while 5% of treated teeth were extracted due to prosthodontic or some other reason. No relation between the incidence of early postoperative discomforts and endodontic failure was found. The incidence of therapy was higher in teeth with primarily closed cavum dentis than in cases with open cavum dentis prior to therapy. PMID- 2100387 TI - [Effect of tramadol on provoked potentials of dental pulp]. AB - The central-acting analgetic (tramadol 50 mg) demonstrated significant effects on wave latencies of provoked potentials in females. However, the same doze had no significant effect on wave latencies of provoked potentials in males. Tramadol provoked a statistically significant reduction of all wave amplitudes of provoked potentials of dental pulp in both sexes. Thus, provoked potentials recorded under this condition gave an "objective" index of tramadol analgetic effects. PMID- 2100389 TI - Medical need for quality specifications in laboratory medicine. Report from th Friibergh Herrgard Seminar. April 23-24, 1990. PMID- 2100388 TI - [Objective methods of measurements of dental mobility]. PMID- 2100390 TI - Analytical goals revisited in the 1990'ies. PMID- 2100391 TI - The quality concept and its specification. PMID- 2100392 TI - The NORDKEM project and its aims. PMID- 2100393 TI - The quality needed for measuring glycated haemoglobin. An application. PMID- 2100394 TI - Quality specifications for clinical chemical analyses used to monitor patients with diabetes mellitus. PMID- 2100395 TI - Medical needs in the evaluation of thyroid dysfunction. AB - The clinical examination has low sensitivity and specificity for the diagnosis of thyroid dysfunction. There is still, however, no consensus as regards the cost effectiveness of biochemical screening for thyroid dysfunction; of possible target groups women post partum might be of particular interest. Current methodological developments center around thyrotropin (TSH), free thyroxine (T4), anti-thyroperoxidase antibodies and indicators of thyroid hormone action, and topics of main concern are the precision at low TSH concentration, the calibration of free T4 assays, and the precision of those assays of free T4 which claim higher accuracy compared with "one-step" methods. Thyroid function indices in non-thyroidal illness continue to confuse assayists. The clinical spectrum of conditions which lead to low serum TSH concentration is insufficiently explored. PMID- 2100396 TI - Iron deficiency. PMID- 2100397 TI - Primary care. PMID- 2100398 TI - Comments. Which tests should be decentralized to the primary health care? PMID- 2100400 TI - Medical need for quality specifications within laboratory medicine. PMID- 2100399 TI - Quality specifications in laboratory medicine. PMID- 2100401 TI - General administrative and economical aspects. PMID- 2100402 TI - The Nordic Protein Project. PMID- 2100403 TI - External quality assurance model for improvement of specificity and accuracy of serum hormone determinations in the Nordic countries. PMID- 2100404 TI - Quality specifications. PMID- 2100405 TI - Some methodological aspects on quality assurance in laboratory medicine. PMID- 2100406 TI - Plans for obtaining a "Nordic list" of specifications. PMID- 2100407 TI - Measuring cholesterol. A handbook for out-patient clinics and laboratory personnel. PMID- 2100408 TI - Quality control and quality requirements for the measurement of glycated hemoglobin. PMID- 2100409 TI - List of planned associated projects in the NORDKEM project 5/89 on medical need for quality specifications in laboratory medicine. PMID- 2100411 TI - An unidentified macromolecular inhibitory constituent of calcium oxalate crystal growth in human urine. AB - We have detected and isolated a macromolecular constituent in normal human urine possessing calcium crystal growth inhibitory activity. The purification procedure consisted of two anion exchange chromatographies and one affinity chromatography. The crystal growth inhibitor was found to be heterogeneous in net charge as well as in size. It has not been identified. It is not an uronic acid-containing glycosaminoglycan, hitherto presumed to be responsible for the inhibitory activity. Whether an urinary fragment of inter-alpha-trypsin inhibitor is responsible has yet to be resolved. PMID- 2100412 TI - Effects of urinary macromolecules on the crystallization of calcium oxalate. AB - The macromolecular fraction of urine with a molecular weight above 3,000 was isolated by dialysis. In the dialysed urine the rate of calcium oxalate (CaOx) crystallization was reduced both in the presence and absence of CaOx seed crystals. There was a clear relationship between crystallization and the relative concentration of the dialysed urine, with the highest crystallization propensity at the lowest concentration of macromolecules. Dilution of dialysed urine also affected crystal size distribution, with a predominance of small (2.8-4.5 microns) crystals in 100% dialysed urine and of large (5.6-14.0 microns) crystals in 5% dialysed urine. This is consistent with a macromolecular inhibition of both crystal growth and aggregation. Analysis of the crystal size distribution 120 min after supersaturation of whole urine to a level at which approximately 100 crystals in the size interval 3.5-5 microns were detected in a Coulter counter surprisingly disclosed a higher mean crystal volume in urine samples from normal subjects than from stone formers. This gives support to the assumptions that macromolecules might be of importance during the initial phase of CaOx crystallization and that urine from stone formers and normal subjects might be different in this respect. PMID- 2100410 TI - Rationale for immunotherapy of renal cell carcinoma. AB - Metastasis to distant organs is the principal cause of death from renal cell carcinoma (RCC). No commonly accepted therapy is available for disseminated RCC at present. Immunotherapy is a mode of therapy that either interferes with the immune system or makes use of drugs that have been derived from soluble mediators of the immune system. Several lines of evidence suggest that combinations of genetically engineered cytokines (e.g. interleukin-2 and interferon alpha) may be particularly active in the treatment of advanced RCC. There are two major rationales for considering immunotherapy for RCC: (1) there is currently no other therapy available, and (2) there is hardly any innovative approach besides immunotherapy. Still, immunotherapy is far from being a standard therapy for disseminated RCC. PMID- 2100413 TI - Urinary crystal surface binding substances on calcium oxalate crystals. AB - In order to study the effect of urinary crystal surface binding substances (CSBS), we extracted the naturally existing CSBS from urine from healthy individuals by conducting homogeneous crystallization of calcium oxalate. CSBS proved not to be promoters but rather strong inhibitors of calcium oxalate crystal growth and aggregation. It is suggested that CSBS exhibited their inhibitory effect by masking the growing sites and aggregating sites on the crystal surface. As for the characteristics of CSBS, we found around 10 peaks of molecular weight, and all of them contained both peptides and saccharides. The findings suggest that CSBS are composed of various kinds of glycoproteins and proteoglycans. PMID- 2100414 TI - Effects of oral pyridoxine upon plasma and 24-hour urinary oxalate levels in normal subjects and stone formers with idiopathic hypercalciuria. AB - The effect of pyridoxine hydrochloride, 200 mg/day (0.97 mmol/day) for 3 weeks, upon plasma and urinary oxalate has been determined in ten normal subjects and seven patients with idiopathic hypercalciuria while both groups were on low oxalate diets. Patients had higher basal urinary oxalate levels than normal subjects. In normal subjects pyridoxine administration decreased plasma oxalate levels and raised urinary oxalate. The patients showed no change in either plasma or urinary oxalate. PMID- 2100415 TI - Recurrences during a 10-year follow-up after first renal stone episode. AB - Each of 92 patients in a Swedish district served by only one hospital had been treated for their first renal stone in 1977 and was evaluated 10 years later. Recurrent stone formation during the observation period was observed in 26% of the patients, with no difference between men and women. Of all the patients who had sought medical advice in 1977 because of urinary stone colic, 51% were experiencing their first stone episode. Ten years later 37% of the original patients were still classified as single stone formers. The recorded recurrence rate was lower than that previously reported in the literature. PMID- 2100416 TI - Studies on the crystallization of magnesium ammonium phosphate in urine. AB - The crystallization of magnesium ammonium phosphate (MAP) was studied in salt solutions and dialysed urine at similar levels of MAP supersaturation. At pH levels of 7.1 or higher crystallization occurred to the same extent in solutions with and without urinary macromolecules. Whereas crystals in the size range 3.5-5 microns were observed in the salt solution at pH 7.0, this was not so in dialysed urine. When the crystal size distribution was determined after 30 min larger crystals were observed in dialysed urine, indicating a promoting effect by urinary macromolecules on the formation of MAP crystals. A modified AP(MAP) index was formulated based on calculations with the EQUIL 2 programme in order to improve the relationship between this simplified estimate and the ion-activity product of MAP (APMAP). This index had the following form: [formula: see text] for 24-h values of magnesium (Mg), ammonium (NH4), phosphate (P), pH and urine volume (V). The APMAP required for the formation of 2,000 crystals in the size range 3.5-5 microns varied between 226 x 10(-15) and 293 x 10(-15) (mmol/l)2 in dialysed urine. An experimental system was designed based on the measurement of pH during the addition of NH4OH. At the point assumed to correspond to the start of crystallization, AP(MAP) index values between 409 and 903 were recorded. Such a test might provide useful information on the crystallization properties in urine. PMID- 2100417 TI - Effects of serum, albumin and immunoglobulins on urease-induced crystallization in urine. AB - The effects of serum, albumin and gammaglobulins on urease-induced crystallization have been studied in synthetic and in human urine. Serum and the studied proteins increased urease enzymatic activity in synthetic urine. In human urine only serum had this effect. In synthetic urine, the proteins and serum markedly decreased the precipitation attached to glass surfaces, while the intraluminal precipitation was increased. In human urine, similar but weaker effects on the precipitation were found for serum and albumin. These findings suggest that the proteins studied, in the concentrations in which they are present in human urine, have profound effects on urease-induced crystallization and may be physiological crystallization inhibitors. PMID- 2100418 TI - How variations in the composition of urine influence urease-induced crystallization. AB - To Study how the composition of urine influences urease-induced crystallization, human urine samples were incubated with urease and the subsequent precipitation measured. Beside the pH increase, the urinary content of magnesium and calcium had profound effects on the precipitation of magnesium ammonium phosphate and calcium phosphate, respectively. Urine phosphate, ammonium and osmolarity had no direct effects on the precipitation. Among the urine components with potential inhibitory properties, only albumin was found to be correlated with such an effect. This inhibitory activity was especially influential in urines with high calcium and magnesium levels. These findings suggest that the composition of urine could also influence the formation of stones consisting of magnesium ammonium phosphate and calcium phosphate. PMID- 2100419 TI - Effects of high-energy shock waves combined with biological response modifiers or Adriamycin on a human kidney cancer xenograft. AB - We have studied the effect of high-energy shock waves (HESW) alone or in combination with biological response modifiers (BRMs) or Adriamycin on the growth of the NU-1 human kidney cancer xenograft. When HESW are administered repeatedly (four sessions of 800 shock waves on days 0, 2, 4 and 6) a prolonged delay in tumor growth was found compared with that following a single administration. This effect was temporary, and several days after stopping the HESW administration the tumor regained its original growth potential (same doubling time). Tumor growth was suppressed for a longer period by the combination of 4 sessions of HESW and a single administration of Adriamycin, 5 mg/kg. Combination of HESW treatment with interferon alpha (5.0 ng/g body weight, three times/week) and tumor necrosis factor alpha (500 ng/g body weight, 5 days/week) s.c. around the tumor resulted in a complete cessation of tumor growth. While Adriamycin had an additive effect on HESW treatment, the combination with BRMs was highly synergistic. PMID- 2100420 TI - Effect of extracorporeal shock wave lithotripsy on bacterial viability. Relationship to the treatment of struvite stones. AB - The aim of this study was to determine whether extracorporeal shock wave lithotripsy (ESWL) affected the viability of the infecting bacteria within a simulated struvite stone matrix. A strain, Proteus mirabilis 28cii, was prepared in three forms: (1) suspended in saline and urine, (2) artificially encapsulated by suspending in agar beads and (3) artificially encapsulated and mineralised by suspending in agar beads with calcium carbonate crystals. The preparations were placed in capped vials partially immersed in degassed water and held in the focal point of the Siemens Lithostar and given 1,000 shocks. Subsequent viability testing showed that bacteria suspended in urine were greatly affected by shock treatments (55% loss in viability), but incorporation into agar beads negated this effect (even if the cells were exposed to 2000 shocks). Mineralisation of the beads with calcium carbonate crystals caused a decrease in viability of 82% that was significantly different from controls. However, this still left 2.3 X 10(8) viable organisms (82% of 2.8 X 10(8], easily enough to form the focus for further infections. A series of control experiments carried out using an ultrasonic cell sonicator probe gave comparable results to those obtained with ESWL. These results demonstrate the ESWL treatment of infected stones must be accompanied by antimicrobial coverage. PMID- 2100421 TI - The effect of indomethacin and metamizole on ureteral motility and urine flow in sheep. AB - The objective of this study was to evaluate the effect of two non-steroid anti inflammatory drugs, indomethacin and metamizole, on ureteral peristalsis during acute occlusion similar to the situation in renal colic. In 12 pentobarbital anesthetized sheep, both ureters were cannulated and the frequency of ureteral contractions, urine flow, mean ureteral pressure and blood pressure were recorded during 10-min control and i.v. drug administration periods. Both indomethacin (1 2 mg/kg) and metamizole (60-120 mg/kg) showed a dose dependent reduction in peristaltic frequency without reduction of the mean pressure. In addition, the pressure amplitude of the peristaltic waves was also lowered, particularly with indomethacin. Only indomethacin reduced the urine flow. Arterial blood pressure was elevated by both drugs, particularly after the first dose of indomethacin. It can be concluded that indomethacin and metamizole reduce ureteral peristaltic frequency, probably blocking the impulse transmission at the ureteropelvic junction. PMID- 2100423 TI - [Insulin and thyroxine levels in dairy cows during lactation and after a 9-day fast]. AB - The aim of the study was to observe the effect of longer fasting of dairy cows during lactation on the insulin and thyroxine levels in blood serum. The test was performed at the Research Institute of Animal Production, Nitra. The blood samples for determination of the hormone levels were collected in the morning from the vena jugularis of four fasted 4-5-year-old dairy cows of the Black Pied breed during lactation with an average daily performance of 16.91. The blood was collected on the first, fifth, sixth, seventh, eight and ninth day (fasting) and then on the fifteenth and twenty first day of the test (feeding). The insulin level in the blood serum of fasted dairy cows was more or less balanced till the seventh day of fasting, and ranged from 4.33 to 4.91 microU.ml-1. On the last two days of fasting, the insulin level increased up to 7.11 microU.ml-1 on the 9th day of fasting. The insulin level was significantly higher during feeding than during starvation. The thyroxine level was statistically significantly lower in fasted dairy cows. Increasing insulin level at the last two collections of the fasting period was probably closely connected with the shifting of the endocrine balance from dominant position of insulin to the dominance of the growth hormone and glucocorticoids. A comparatively high effect on the increase of the insulin level was exerted during that time also by the increasing amounts of non esterifed fatty acids. Starvation significantly reduced the levels of the studied hormones in dairy cows during lactation. PMID- 2100422 TI - Long-term observation of the detrusor smooth muscle in rats. Its relationship to ovariectomy and estrogen treatment. AB - We studied the bladders of 24-month-old intact rats, rats that had been ovariectomized at the age of 6 months, and intact and ovariectomized rats treated by estrogen from the age of 16 months. The study thus comprized four groups: group I: bilaterally ovariectomized rats; group II: intact rats; group III: ovariectomized rats treated with estrogen; group IV: intact rats treated with estrogen. The weight and collagen concentration of the bladders were determined. The ovariectomized bladders weighed significantly less and had a higher collagen concentration than the intact bladders. Estrogen substitution for ovariectomized rats reversed these parameters. Detrusor strips were also used for organ bath studies. All bladders were similar in regard to the nerve-mediated frequency response relationship. The atropine-resistant response was studied by adding scopolamine to the organ bath. Strips from ovariectomized rats had a significantly diminished atropine-resistant response, which was abolished by estrogen substitution. The present study suggests that micturition problems in menopause might have a structural as well as a pharmacological explanation. PMID- 2100424 TI - [Coagulase negative staphylococci isolated from cow milk]. AB - The species composition was determined in the set of 52 randomly selected strains of coagulase-negative staphylococci, which were isolated from the milk of dairy cows in 1989. Of this set of strains, the following species were identified: Staphylococcus hyicus subsp. chromogenes (26.9% strains of the set), S. hyicus subsp. hyicus (10.3%), S. xylosus (19.3%), S. saprophyticus (11.5%), S. warneri (9.6%), S. haemolyticus (9.6%), S. hominis (3.8%). Attention is drawn to the increasing occurrence and significance of coagulase-negative staphylococci from the point of view of mastitis in dairy cows. PMID- 2100425 TI - [Determination of the effects of feeding cold soured milk to calves under normal conditions]. AB - The effect of cold milk drink on selected biochemical and haematological parameters in calves blood during the milk nutrition period was observed in farm conditions, as compared with the current feeding regime. The test group was offered cold sour milk drink (one 1 MKS Laktosan acidulated with addition of 22 ml formic acid to a pH of 4.6) at the temperature of 16 degrees C after four-day adaption till the calves average age of 61 days. The control group was given MKS Laktosan in the usual way, using the same amount of the drink and time of serving it. During the test the performance was recorded, as well as haemoglobine content, total protein, haematocrit, urea, glucose, cholesterol, transaminase (ALT and AST) activities and alkaline blood reserves. In the studied parameters no significant differences were found between the test and control group (P greater than 0.05). The average daily gains of live weight during the period of milk nutrition was 0.762 kg in the test group and 0.667 kg in the control group. PMID- 2100426 TI - [Relation of heat resistance tests and sperm survival to pregnancy and fertility in sows]. AB - Sperm of 28 boars of the Landrace breed was evaluated with the help of the thermoresistance test (TRT). The principle of the TRT is that the sample of fresh sperm is left in a 38 degrees C bath for 120 min and after that time the activity of the sperm is evaluated. 308 ejaculates were evaluated in this way and 1342 sows were inseminated by these ejaculates after a short storage. The highest conception rate was stated after insemination with the sperm whose activity was above 50% at the end of the TRT. 366 of 400 sows became pregnant, i.e. 82.43%, whereas out of 370 sows inseminated with sperm whose activity was 0-30% at the end of the TRT only 269 conceived, i.e. 72.70%; difference was statistically highly significant. No statistically significant difference was recorded between the fertility (number of piglets per one litter) and the TRT results. A significant dependence was observed between the sperm survival after 72 hours and conception (P less than 0.05). The same significant relation was found between survival within 72 hours and TRT in fresh ejaculates. This justified the recommendation to introduce the TRT among the test used for evaluation of the quality of fresh boar ejaculate. PMID- 2100427 TI - [Biometric parameters of the uterus, ovaries and levels of 17 beta-estradiol (E2) after delivery in sheep]. AB - Biometric changes of uterus, ovaries, follicles and 17 beta-oestradiol (E2) concentrations were investigated in 15 lambing ewes of the Slovak Merino breed in the puerperal period. The sex organs were excised immediately after bleeding from ewes slaughtered on days 1, 7, 17, 25 and 34 post partum (p. p.). Biometric parameters of the body and horns of uterus were measured by a calliper. The ovaries were weighed on an analytical balance, their length, width and height were measured at the same time. The size and number of follicles were determined on the ovary surface. The blood for E2 detection was collected from vena jugularis three and one day before delivery (days -1, -3). Blood samples were also collected after delivery on days 1, 7, 17, 25 and 34. E2 concentrations in the blood serum of ewes were determined by RIA-test-ESTRA kits, designed in one institute at Kosice. The highest weight of uterus body in the test ewes was recorded on day 1 p. p. In the following days the weight of uterus body had a decreasing trend. There were significant differences in the weight of uterus body from day 17 to day 34 p. p., in comparison with the first day after lambing (P less than 0.01). A significant decrease in the length of uterus body was observed from day 17 to day 34 of observation (P less than 0.01; P less than 0.001). An increase in the length of a nongravid horn, observed on day 7 p. p., was followed by a gradual decrease until day 34, similarly like in its weight. No statistically significant differences were found out in the ovary length, width and height. Neither were any greater changes recorded in the weight of ovaries from day 1 to day 34 after delivery. The highest number of small structures (28) observed on day 7 p. p. in the ipsilateral ovary was decreasing in the course of puerperium and the number of follicles larger than 2, 4 and 5 mm was increasing. The highest concentrations of E2 were not recorded on day -1 before delivery. The significantly lowest concentrations of E2 were recorded on day 25 p. p. The above mentioned results are preliminary and they enlarge the knowledge of biometric parameters of uterus, ovaries, follicles and E2 concentrations after delivery in ewes. PMID- 2100428 TI - [The effect of dry standing time in cows with the obesity syndrome on selected indicators of metabolism and the state of their calves]. AB - Differences in the composition of the blood (plasma) and urine of cows were evaluated in groups (n = 8) with a normal time of dry standing (50-60 days) and in cows standing dry for 80 to 124 days. Two approaches were used: repeated examination of the same animals two to three weeks before parturition and six to eight weeks after parturition, and single examination of the cows being in the same stage of reproduction cycle. A number of changes were recorded, testifying to a reduction of the function of the adrenal glands and to a decrease in the activity of the liver in the cows left to stand dry for a longer time. The calves of these cows had changes in their blood (plasma), indicating a hypofunction of the adrenal glands and a reduced phagocytic activity of the leucocytes, one of the parameters of the immunity system. PMID- 2100429 TI - [Biologic characteristics of mycobacterium strains isolated from cattle from herds with clinical paratuberculosis]. AB - In the period from 1983 to 1986, bacteriological examination for paratuberculosis was performed in 263 samples of lymph nodes, intestinal mucous membrane and excrements of cattle, kept on a farm where clinical paratuberculosis occurred. Seventy-nine strains of mycobacteria were isolated during the culturing. On selective agar medium with mycobactin as the growth stimulator, 71 strains were isolated which had failed to grow on the conventional mycobacterium-culturing media. In the subculture, the dependence of mycobacteria on the mycobactin declined and the number of mycobacterium strains growing in the subculture on conventional mycobacting-free media doubled. Two thirds of the mycobacteria which did not depend on mycobactin during growth exhibited the same antigenic properties as Mycobacterium avium 1, 2, 3, 8 during serotypification. Ability to induce sensibility to PPD avian tuberculin or paratuberculin was demonstrated during the bioassays of mycobactin. Almost a half of the strains inducing animals' sensitivity to the above-mentioned allergens were found to be virulent to pullets that had tuberculosis in their parenchymatous organs. Of the laboratory animals, the highest virulence of the mycobactin-dependent mycobacterium strains was demonstrated in mice subjected to intravenous infection, accompanied by hyperplasia of the spleen, with reisolation of the mycobacterium culture within six eight weeks after infection. PMID- 2100430 TI - [Changes in blood levels of progesterone, triiodothyronine and thyroxine and the results of quantitative histological analysis of the placentoma and corpus luteum in cows after prolonged labor]. AB - Changes in the cell structure of the placentoma and the corpus luteum were subjected to quantitative histological investigation, parallel with the examination of the concentrations of progesterone (P4), triiodotyronine (T3) and tyroxin (T4) during parturition (Oth hour) and two and six hours after parturition. The hormone concentrations were determined by the RIA method. The results of the quantitative histological analysis of the placentomae and the corpus luteum suggest that when the placenta is retained there is a significantly higher number of maintained epithelial cells in the placentoma crypts and a higher number of unchanged small, dark and large, light lutein serraetion cells in the biopsy of the corpus luteum during the period under investigation. The morphological finding significantly correlates with higher concentrations of P4 in the blood of the cows with retained placenta, as compared with those whose placenta was not retained. It can be derived from the pattern of changes in T3 and T4 concentrations, compared with P4 and with the histological finding, that there is a functional relationship between the placentoma, corpus luteum, and the thyroid gland. PMID- 2100431 TI - [Nonspecific immunostimulating activity of Bordetella bronchiseptica bacterin in tests on mice and calves]. AB - Three experimental models were used to verify the effectiveness of immunostimulant preparations of microbial origin. Of the four microbial species, used in the tests with the stimulation of mice against subsequent infection with the virulent strain of Pasteurella multocida, the highest resistance-increasing power was recorded in Bordetella bronchiseptica. There were large differences in stimulation activity between its strains, ranging from those with a low activity up to strain 6229, which increased the LD50 of the infected mice to a level 72 times as high as in the control. The differences in the survival of the mice also varied within the range between immunostimulation and infection, the best effect being obtained when the mice were stimulated 48 h before the infection. No significant difference was recorded between the use of the bacterin of B. bronchiseptica alone or B. bronchiseptica bacterine with oil adjuvant. The immunostimulant activity of B. bronchiseptica was also demonstrated in the model of sublethally irradiated mice in which the preventive administration 24 h before irradiation led to earlier and faster regeneration of the lymphoid tissue: this led to a higher weight of the spleen, to an increase in the number of peripheral leucocytes, and increased activity of chemiluminiscence six days after irradiation. The bacterine of B. bronchiseptica was also used at different concentrations and in combinations with other substances to stimulate two-month old clinically healthy calves. The most pronounced effect was obtained after the administration of B. bronciseptica bacterine with oil adjuvant and after administration of the same substances together with vitamin A: twenty-four hours after these treatments there was an increased number of peripheral leucocytes and after 2-4 days an increased activity was observed in the MSHP particle phagocytosis test and in the chemiluminiscence test. The activity of lymphocytes in the blastic transformation test was insignificantly increased seven days after stimulation. PMID- 2100432 TI - [The effect of short-term fasting on sleep in pigs]. AB - Trials were conducted with twelve piglets of the German Large White breed, intended for fattening. Their age was 56 +/- 2 days and their average weight was 21 +/- 3.7 kg. The piglets were studied for the effect of short fasting on the time and nature of sleep. After 18 hours of fasting (skipping the morning feeding), the piglets were fixed to obtain a combined record, including the electroencephalogram (EOG). This record was used for analyzing the time of waking and sleep, both the NREM stage and REM episodes. The same observations were performed in the piglets after feeding. The differences in the obtained data between the groups of animals were subjected to statistical evaluation. The fasting animals slept for about 15% of all the time under study and their sleep included short NREM periods interrupted by waking. No REM sleep was observed in the fasting piglets. After feeding the piglets slept significantly longer (p less than 0.01), more than half the period of study. Episodes of REM sleep occurred repeatedly in four animals. It is indicated by the results that fasting reduces the length of sleep and the nature of sleep. PMID- 2100433 TI - [A simple immunologic skin test in piglets]. AB - A simple immunological skin test was carried out on 73 weaned piglets at a weight of 15 to 30 kg. Bristles on the piglets' back were shaved off and 0.1-ml amounts of four substances were injected intradermally. These were an isotonic solution of sodium chloride (900 micrograms NaCl in 0.1 ml), histamine (100 mu g in 0.1 mu l), phytohaemagglutinin (200 mu g in 0.1 ml), and a staphylococcus lysate (STAVA). The sites of administration of the substances were 5 cm apart. The dermal reaction was evaluated 20 minutes, 24 and 48 h after the i.d. administration. The size of the papule (measured after 20 min) and the size of the induration (after 24 and 48 h) were measured in two perpendicular directions and the mean value was calculated from the measured data. The average size of the papule was 8.1 mm 20 min after administration of sodium chloride (NaCl) and 19.6 mm 20 min after administration of histamine (HIS). The average size of induration after the administration of phytohaemagglutinin (PHA) was 13.1 mm after 24 h and 11.0 mm after 48 h. The average size of the papule was 11.1 mm 20 min after the administration of STA, the average size of induration was 10.6 mm 24 h after administration of STA and 8.5 mm after 48 h. Piglets that had papule larger than 15 mm 20 min after HIS administration (after subtracting papule size after NaCl administration) were regarded as piglets susceptible to states of allergy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100434 TI - [Analysis of mammary gland tumors in dogs in the South Bohemian Region]. AB - 149 biopsies and excisions of tumorous tissues of the mammary gland it bitches were examined histologically at a workplace of the State Veterinary Institute at Ceske Budejovice in the years 1970 to 1987. The tumours were classified according to the criteria recommended by the WHO classification system. The tumours were divided into three groups with respect to their histogenesis: epithelial (58.4%), mesenchymatous (2%) and mixed (39.6%). The ratio of malignant to benign tumours made 65.1% to 34.9%. PMID- 2100435 TI - [Use of methacrylate for internal fixation of fractures in small animals]. AB - An experiment was conducted to verify the possibility to use the self polymerizing metacrylate resin DURACRYL EXTRA, commonly used in dental prosthetics, for simple fixing of fractures in small animals. The metacrylate was placed in a very small distance from the bone and the generally available surgical materials were used to connect it with the bone fragments (Kirschner's wires and surgical wire). Tree types of diaphysial fractions of femur and humerus were evaluated in a group of rabbits, dogs and sheep. The histological study of the reaction of the adjacent soft and hard tissues to metacrylate in the stage of healing of fracture is documented by the normal course of the reparative processes with no signs of more serious non-adequate reaction. The method of using the resin is generally simple, inexpesive and has low requirements for the use of instruments. This promises broad use in practice in the treatment of other kinds of fractures, mainly in those cases where there is a lack of special equipment for the surgery of bones. PMID- 2100436 TI - [Posterior restorations with composites]. PMID- 2100437 TI - [Root fractures and tooth luxation. 3]. PMID- 2100438 TI - [Implants in edentulous mandible--theory and practice. 1. Theoretical considerations]. PMID- 2100439 TI - [Clinical procedures with Caridex system]. AB - Caries removal was performed with the Caridex-System in 40 patients with caries lesions. The clinical results after 6 and 12 months as well as the light microscopic and scanning electron microscopic examinations showed, that this new method is useful and effective in dental practice. PMID- 2100440 TI - [Pitt-Easy Bio-Oss implant system in use as immediate implant in anatomically difficult cases]. AB - The implantology has become more important in the last years. Often the dentist on the field of implantology has to treat patients of which the anatomic situation is not allowing an implantation in the jawbone. The presented paper will show possibilities to treat a wide range of cases with a special implantation system. Specially it will discuss by implanted examples the application of the Pitt-implant as an urgent-implant in difficult critical cases. PMID- 2100441 TI - [First clinical and materials experience with full porcelain crowns and In-Ceram bridge system]. AB - The all-ceramic crown- and bridge-system In-Ceram uses a glass-infiltrated, sintered alumina-ceramic core material. The construction of bridges seems to be possible due to the high bending strength of the core material. The results concerning marginal fit and aesthetics are very pleasing. However, long-term results with this material are not available. PMID- 2100442 TI - [Influence of conservative periodontal treatment on degree of gingival inflammation]. AB - Assuming that conservative periodontal therapy is essential and important for the further surgical therapy, it was the purpose of this present study to investigate the effect of conservative periodontal therapy of gingiva. 50 patients were examined. Significant reductions of plaque index (42%) and bleeding index (29%) were obtained and statistically significant. PMID- 2100443 TI - [Posterior restoration with porcelain. Search for position]. PMID- 2100444 TI - [Implantation in edentulous mandible. 2. Practical demonstration]. PMID- 2100445 TI - [Alternate method for closure of oro-antral fistulas. Plastic covering of jaw opening with lyophilized Dura and alcoholic solution of Prolamin]. AB - The operative closure of an oroantral fistula due to tooth extractions by the method of Rehrmann consists of various disadvantages, e.g. postoperative pain, swelling, flattening of the vestibulum and scar-tissue. Two alternative methods to close fresh oroantral fistulas without surgical intervention are described. By the use of prolamin occlusion gel or lyophilized dura these disadvantages can be avoided. Both techniques were successfully attempted on patients. The rate of failure is on both counts under 4%. Some indications limits must be strictly regarded. Both methods are really a good alternative to the usual operative procedure of Rehrmann and can easily be applied even on patients of great risk. PMID- 2100446 TI - [Indications and preparation of a fluoride splint]. AB - The individually produced fluoride miniplastsplint is suitable for application in preventive dentistry, for the therapy of cervical demineralisation and hypersensitive root surfaces. The models must be measured with a "parallelometer" so that the exactness and tightness of the splint can be guaranteed. A space with room for occlusal stops guarantees the necessary place for the gel containing fluorides. The patient must wear the splint once a week for half an hour. PMID- 2100447 TI - [Metal-porcelain bonding in precious metal dental alloy]. AB - The metal-ceramic bond of a dental alloy free of non-precious components was investigated in bending and three-point-bending test. Light and scanning electron microscopic examination as well as wavelength dispersive x-ray analyses were carried out. They showed no alterations in structure or concentration of the components in the area of the metal-ceramic boundary, due to diffusion and oxidation processes in the extent known from conventional bonding alloys. The results lead to the conclusion that the tested alloy is suitable for ceramic veneering under limited indication. PMID- 2100448 TI - [Osteoplastic procedure for cystic processes in posterior mandibular region]. AB - This Report deals with surgical treatment of the extended osteolysis processes for the mandibular posterior tooth area. It will show the advantages of an osteoplastical method of operation. According to a case report the therapy of an extended solitary bone cyst will be carried out with an apisectomy of the molar 46 at the same time. PMID- 2100449 TI - [Implantation with fixed bridge substitute. 3. Linkow blade implantation]. PMID- 2100450 TI - [Computer assisted occlusal diagnosis in complete dentures]. AB - The T-Scan system for computerized occlusal diagnosis was tested in laboratory and clinical experiments. The lowest force level producing a display was approximately 1 N when loading the sensor by a rod with a diameter of 0.5 mm. The sensitivity depended considerably on the position of the testing point on the sensor. In the clinical study contacts in intercuspal position were evaluated as well as the possibility to identify artificial premature contacts. After remounting experiments were carried out in the articulator and in patient's mouth. The results lead to the conclusion that the use of the T-Scan system in complete dentures is limited to the rough evaluation of the occlusal situation. PMID- 2100451 TI - [Use of CO2 laser in treatment of oral soft tissues]. AB - Within a period of 36 months 416 patients have been treated with a CO2 laser in different cases of oral soft tissue indications. The precise excision of the tissues was done with a power of 4 watts. The results of the clinical study show that the use of a CO2 laser in surgical procedures on oral soft tissues is superior compared to classical treatment by scalpel in many cases. PMID- 2100452 TI - [Use of titanium in conservative dentistry]. AB - Non alloyed titanium is characterized by an excellent resistance to corrosion, a relatively low thermal conductivity, a good ductibility and biocompatibility. Furthermore the costs for this material are very low. First clinical experiences with respect to inlays, onlays, partial and full crowns fabricated out of this metal can be classified as positive. Problems in processing cast titanium (e.g. reduction of the material, polishing) should be solved by the development of special instrument sets. PMID- 2100453 TI - [Value of squamous cell epithelial-associated (SCC-) antigens in early diagnosis of oral carcinoma]. AB - The diagnostic value of plasma concentration of the squamous cell carcinoma antigen was examined in 75 cases of pretherapeutic squamous cell carcinoma of the oral cavity. A pathologic plasma level was found in 32% of the tumour patients at time of diagnosis. The incidence of elevated SCC- values was inversely correlated to the tumour grading. A direct correlation of the sonographically measured total tumour volume was seen. As predominantly more extended tumours show pathologic values, SCC-Antigen is not a marker for the screening in the diagnosis of the early cancer of oral cavity. That emphasizes the importance of the precise clinical examination of each patient. In cases of elevated pretherapeutic values SCC-Antigen is very useful for therapy--monitoring and follow-up. PMID- 2100454 TI - [Study of temperature of composite resins during polymerization]. AB - Temperature was measured during polymerization of 24 composite materials within 5 minutes (up to 10 minutes) after starting polymerization. A sudden rise (10 K-18 K) of temperature could be observed in most of the materials; soon afterwards the primary situation was reached again. The measured high temperatures should be considered to might be one of the factors, which lead to an affection of the pulp tissue. PMID- 2100455 TI - [Posterior restorations with gold]. PMID- 2100456 TI - [Root fractures and tooth luxation. 2]. PMID- 2100457 TI - [Considerations of cover denture prostheses]. AB - The long experience in the production of clear mucous membrane-carried total prosthesis shows, that's very important to include telescope holding elements into the dental care. In the cases of elderly patients, the transition to a total prosthesis and getting used to wearing it should not be underestimated. PMID- 2100458 TI - [Dental treatment methods using the loupe]. AB - The use of magnifying loupes in dentistry enhances the accuracy of working procedures. The precise fit of laboratory completed restorations can also be more easily controlled. Meticulous tasks such as caries excavation, the bonding technique, restorations, periodontics and surgical procedures are all greatly improved by clearer and better vision. Especially in the relatively new field of restorative cosmetic dentistry, with the adhesive technique, a high level of precise work is required. Caries excavation, enamel etching, bond application, as well as the finishing of restorations with special attention being paid to the enamel area and adjacent teeth are all difficult procedures, and are all greatly simplified by using magnifying loupes. PMID- 2100459 TI - [Periodontal-orthodontic treatment possibilities for migrated front teeth--case selection and theoretical concept]. AB - Migration of maxillary incisors caused by advanced periodontal disease induces functional, periodontal and esthetical problems to the patient. Under certain conditions a combined periodontal-orthodontal treatment should be considered. A successful treatment result depends on the selection of the patients. The presented concept offers good long-term results for a combined periodontal orthodontal therapy. PMID- 2100460 TI - [Visibility of front and side teeth]. AB - Anterior and posterior tooth visibility was analysed in a population of 220 subjects. Scoring photographic data gave the percentages of anterior and posterior teeth shown in different situations: speaking, laughing, exaggerated smiling. The consequences for planning and manufacturing dentures are shown by examples. PMID- 2100461 TI - [Complications of daily dental work and expert opinion aspects]. AB - Complications in dentist's daily work are discussed by aspects of prevention and possible consequences. The procedure in fact of incidents is described to guard against the reproach of malpractice. PMID- 2100462 TI - [Deformation of crown margins by porcelain fusion]. AB - This study attempted to measure marginal distortion of the porcelain-bonded-to metal restoration due to porcelain fusion, 40 crowns were made of a PdAg-alloy on two dies with different extensions of the bevelled shoulder preparations. Only four crowns fit on the original dies after the firing procedure. Dimensional changes within oxide bake as well as dentine and glaze bakes could be achieved. Crowns with extended vestibular margins showed a higher amount of relative distortion. In a second simple experiment dimensional changes caused by the PFM process could be found for other Au- and Pd-based alloys too. PMID- 2100463 TI - [Front tooth trauma--endodontic aspects]. AB - In a short review indication, possibilities and frontiers of modern endodontic treatment concepts for traumatized teeth are summarized. PMID- 2100465 TI - [Periodontal-orthodontic treatment possibilities for migrated front teeth. Possibilities and limits of orthodontic therapy]. AB - An interdisciplinary approach for the rehabilitation of patients with pathologic tooth movement caused by advanced periodontal disease is presented. The special demands to the orthodontic therapy are illustrated by a case report. The necessity for precise treatment planning and for the use of controlled treatment is demonstrated. PMID- 2100464 TI - [Universal adhesive in restorative dentistry]. AB - The dental enamel adhesives are in clinical use for many years. Adhesive dentistry with the acid-etching of enamel has proven reliable, because bond strengths reach the internal strength of enamel prism components. The new universal bonding agents are performing well on enamel and dentin. Because of the hydrophilic character of the adhesives promise higher and faster bond strengths to dentin as shown in many short-term studies. The problematic aspects will be discussed. The step-by-step-procedure in a class V-restoration demonstrates the clinical application. PMID- 2100466 TI - [Material study for Aumatic foil technique]. AB - The disadvantage of conventional metal ceramic restorations seems to be the loss of transluszenz and transparency in thin ceramic layers, on behalf of Aumatic foil an improved aesthetic image is possible. Foil-technique enables the production of metal ceramic crowns with a compressive and shearing forces allowing the appliance to single crown in clinic use. In vitro measurement of the marginal leakage show a sufficient adaptation. PMID- 2100467 TI - [Selenium as an antidote for mercury?]. PMID- 2100468 TI - [Investigation of "confectioner's caries" in bakers and confectioners]. PMID- 2100469 TI - [Esthetic aspects of biometric layering technique]. PMID- 2100470 TI - [Quality control with dental probe?]. PMID- 2100471 TI - [Psychosomatics as connecting link in dentistry]. PMID- 2100472 TI - [Gerostomatology--a real problem for practice or an alibi for the science]. PMID- 2100473 TI - [Occlusal deformation as "body jewelry"--extent, motives and background]. PMID- 2100474 TI - [Anorexia nervosa and bulimia nervosa--psychogenic occlusal damage and its significance for the dentist]. PMID- 2100475 TI - [Galvanoceramic crowns. Clinical and experimental results]. PMID- 2100476 TI - [Psychosomatic aspects of dental anamnesis. The "difficult" dentist-patient connection]. PMID- 2100477 TI - [Dentistry in late Middle Ages: deer kidney fat for pain]. PMID- 2100478 TI - [Cleft lip surgery in "Frauendienst" 1255]. PMID- 2100479 TI - [Magnetic attachments for implants in complete dentures]. AB - In this research work we examine and apply to patients new types of technologies, describing advantages and disadvantages of using them. This osseointegrated implantation with magnetic prosthetic connection, allow to stabilize complete denture in patients suffering from serious atrophy. PMID- 2100480 TI - [Class II cavity for amalgam. Proposed new modifications related to material characteristics]. AB - The Authors study conservative preparation designs for Class II amalgam restorations, with and without an occlusal dovetail. They propose the use of a high-copper filing admix allow in Clas II preparation with occlusal dovetail and the use of high-copper spherical alloy in box only restorations. PMID- 2100481 TI - [Cephalometric monitoring of surgical-orthodontic patients with progenic syndrome]. AB - The authors report two cases of severe dentofacial skeletal anomalies, that are analyzed with radiologic diagnostic methods during the treatment. The dentoskeletal variation followed to the orthodontic-surgical therapy and the possible relapses are described. PMID- 2100482 TI - [Emergency situations in the dental office. 3. Pharmacology]. PMID- 2100483 TI - [Oral lipoma]. PMID- 2100484 TI - [Position of the upper incisor after orthodontic therapy with Tweed philosophy and mechanics: statistical study of average incisal variations in 3 Angle dento skeletal classes, with and without extraction]. AB - The skeletal characteristics of dento-alveolar malocclusions condition the orthodontic therapy plane and produce typical and recurrent variables in the final shape in "Tweed occlusion". The study effects with templates made out of cephalometric average values of treatment in the different dental malocclusions, shows direction and amount of therapeutics correction. The behaviour of upper and lower incisors to achieve the normal occlusion is in relation with the characteristics of Angle's Class and with the necessity of therapeutics dental extractions. PMID- 2100485 TI - [Position of the lower incisors in Class II division 1 malocclusion with hyperdivergence and mandibular retrognathism]. AB - The lower incisors are proclined while the maxillary teeth are well positioned in the Class II 1st division malocclusions with retrognatic mandibula. Thus this shouldn't be modified by an orthodontic treatment considering the above factors determinant in this particular facial typology. PMID- 2100486 TI - [Changes in systemic immune function in elderly dental patients]. PMID- 2100487 TI - [Emergency situations in the dental office. 4. Prevention and organization]. PMID- 2100488 TI - [Periodontal problems connected with orthodontic treatment of impacted teeth on high or vestibular eruption]. AB - The authors report four cases of vestibular ectopia. The relevance of a sufficient gums adhesion to dental elements is outlined as a factor leading to an optimal reposition of the latter. PMID- 2100489 TI - [Statistical study of incidence and development of traumatic bone cysts of the jaws]. PMID- 2100490 TI - [Craniofacial dysmorphosis: orthodontic and surgical-orthodontic treatment of borderline cases]. AB - The authors, described the typical cranio-facial anomalies in the border-line cases, consider the possibilities of the orthodontic therapy or else of the alternative orthodontic-surgical therapy. The advantages and disadvantages are commented. PMID- 2100491 TI - [A case of solitary neurofibroma of the tongue]. PMID- 2100492 TI - [The use of a computer in analysis of orthodontic cases]. PMID- 2100493 TI - [Changes in the strength of immune defense of the oral cavity in aging]. PMID- 2100494 TI - [Differential anchorage in orthodontics: problems and clinical implications]. AB - The authors carry out an examination of the principles that lead the "passive" anchorage of the teeth. Furthermore it's considered the possibility to have an different anchorage between two teeth or arch segment with force systems developing different Moment/Force ratio between active and reactive segment. At last, they consider advantages and disadvantages of these systems. PMID- 2100495 TI - [Emergency situations in dental offices. 5. Medico-legal aspects and insurance]. PMID- 2100496 TI - [Photography in orthodontics]. AB - We have analyzed the bases of information about the feasibility of orthodontic photography. After giving details about the photographic equipment and the field lighting we gave a thorough description of the operative modalities of intra and extraoral photos. PMID- 2100497 TI - [Periodontal disease in children]. PMID- 2100498 TI - [Which knee ligaments must be reconstructed in anterior and posterior valgus and varus instability? An experimental study]. AB - This study aims to localize the ligamentous lesions in distinct knee joint instabilities. For that reason 41 human cadaver knee joint specimens were tested in a three-dimensional determined apparatus. Ligaments were successively dissected and forces and torques were introduced. Both cruciates are the dominant structures in preventing straight anterior und posterior movement of the tibia. As a supporting element the postero-medial capsule prevents anterior dislocation in ACL-deficient knees. Therefore extraarticular procedures in cruciate instabilities will not be successful. In contrast varus- and valgus instabilities resulted after transsection of a couple of ligaments. Valgus stability decreased after cutting the medial collateral, posterior oblique and both cruciate ligaments. The most important element in preventing straight varus instability was the lateral collateral followed by the posterior cruciate ligament, while the popliteus tendon had only little influence. Therefore in medial and lateral instabilities all supporting structures should be exposed and reconstructed. PMID- 2100499 TI - [Muscular stabilization of the upper ankle joint in lateral instability. An experimental study]. AB - The mechanical stabilizing effect of artificially applied muscular strength to the peroneal tendons was examined in an experimental study using cadaveric lower legs with unstable ankle joints. Therefore the anterior fibulo-talar and the fibulo-calcanear ligament was dissected and the resulting instability with examination of the anterior drawer sign and the talar tilt was measured under standardized conditions. After initial measurement under standardized conditions a muscular strength of 75 N and 150 N was applied and the resulting stability was measured again. In a second experiment an additional orthotic device was applied and the stability was measured again under applied muscular strength. The results demonstrated that stable conditions at the lateral unstable ankle joint are only achievable when a muscular strength of 75 N (ant. drawer sign) or 150 N (talar tilt) is combined with the application of an orthotic device. For clinical treatment this means that functional treatment for ankle sprains with application of an orthotic device needs additional training for improvement of the muscular strength of the peroneal muscles. PMID- 2100500 TI - [Pain in the knee joint. A report of non-cartilage or meniscus-induced changes. A presentation based on own patients]. AB - Based on experiences made with the arthroscopy of the knee joint in our hospital since 1985 and also based on studies made in treatment of plicae synovialis, 155 patients were operated between 1. January 1987 and 31. December 1989 by an arthroscopy, where only synovial changes are found and treated. In 135 cases the anamnesis, the result of the clinical examination and the operation report are analyzed. 110 patients could be examined postoperative. In listing the results there is made a difference between patients, where a synovial change at the medial condylus is operated and such where synovial changes round the femoropatellar joint are treated. All patients were investigated by a questionnaire action. A discrimination by intraoperative foundings was not made, it should rather be clarified, whether the arthroscopic operative treatment of those synovial changes leads to a removal or a clear reduction of the pain in the knee joint, which exists preoperative and leads to the operative treatment. Especially was asked for changes in sporting activities, because the pain mostly appears at physical exercise. PMID- 2100501 TI - [Complications in 4,000 arthroscopies]. AB - From 1983 to 1989 we performed about 4,000 arthroscopies of the knee in our hospital. Iatrogen lesions of the cartilage were the most frequent complication. Other complications were edemas of the subcutaneous tissue, the necessary of arthrotomy, long operating time, subcutaneous hematomas, postoperative effusion or hemarthrosis and thrombosis. The rate of severe complications was 0.5% as described by other authors. Arthroscopy has a low rate of complications, but it isn't a method without risks. PMID- 2100502 TI - [Arthroscopic treatment of chondropathia patellae with lateral release and motor driven instruments]. AB - The treatment of chondromalacia of the patella is a medical problem. There are no sure concepts of therapy. We have analysed the value of the only lateral release or shaving by motorizised instruments or the combination of both methods. After lateral release have many patients no pain but the other methods also helped many patients. The comparison of these groups is impossible because of the different structure. A prospective randomised study has to bring the answer to this question. PMID- 2100503 TI - [Therapeutic possibilities of shoulder arthroscopy at the orthopedic clinic of the Charite and the surgical clinic Berlin-Weissensee]. AB - We report on arthroscopic procedures of 279 shoulder joints which were done in two hospitals of East-Berlin. We stress out the intention to arthroscopic diagnostic and simultaneous surgery. Arthroscopic surgery was mainly performed as resections and exstirpations. In cases of luxation and severe rotator cuff tears the open revision was necessary to perform. PMID- 2100504 TI - [The value of arthroscopy for diagnosis of instability of the shoulder joint]. AB - As a glenohumeral instability is defined each case of transient recurrent and permanent decentration of the joint. We propose to differentiate primary and secondary glenohumeral instabilities. Arthroscopical diagnostic is helpful to classify the luxation and subluxation and for verify transient instabilities. In cases clinically snapping phenomena were noticed, arthroscopic findings were documented. A relation between those phenomena and arthroscopic findings is discussed. PMID- 2100505 TI - [Arthroscopic synovectomy of the shoulder and elbow joint]. AB - We reviewed experiences and results of six shoulder and nine elbow joint synovectomies, performed in a time period between 1989 and 1990 by arthroscopic technique. The operation technique is pretentious an requires some expenditure. The postoperative course distinguishes itself by little pain and early increase of range of motion. PMID- 2100506 TI - [Early arthroscopy of the knee joint of the athlete also without hemarthrosis?]. AB - Differentiating from the indications to an acute or early arthroscopic procedure in cases of injuries of athlete's knee joints the consequence of an early arthroscopy in this patient group is demonstrated in cases without haemarthrosis. If conservative treatment is unsuccessful an early arthroscopy is particularly indicated in these cases due to the shortening of the required time of treatment. PMID- 2100507 TI - [Carpometacarpal joint arthrosis and its surgical therapy with the de la Caffiniere endoprosthesis]. AB - In the area of the hand the carpo-metacarpal joint of the thumb together with the metacarpo-phalangeal joints is the most important joint according to the function of the hand. Its reduction of movement leads to misfunction of the thumb and the whole hand. Osteoarthritis of that very special joint commonly occurs in females after the menopause. The increasing severeness of the arthrosis is often complicated through pathological positions as well as through contractures (so called Z-deformities). In these patients operative treatment for improvement of function is very often not avoidable. Especially in the elderly patient with reduced manual work the implantation of a cemented carpo-metacarpal prosthesis (created by de la Caffiniere) seems to be a useful treatment. As in all cemented implants the disadvantage is the danger of aseptic loosening of the prosthesis. PMID- 2100508 TI - [Osteosyntheses and arthrodeses of the hand. The intraosseous wire suture]. AB - The intraosseous wiring, using two wires twisted on both sides, is an essential enlargement of the operative techniques of osteosynthesis and arthrodesis at the hand skeleton. Its efficiency results from the bio-mechanical principles of tension-band stabilization and inter-fragmentary compression. Indications are transverse fractures, pseudarthroses and corrective osteotomies of the metacarpals and phalanges, interpositions of bone grafts, replantations and finger transpositions as well as arthrodesis of interphalangal joints. PMID- 2100510 TI - [Indications and technique of talo-crural arthrodesis]. PMID- 2100509 TI - [Sternocostoclavicular hyperostosis]. AB - On the basis of 4 patients from our own records we describe the rare syndrome of "Hyperostosis sternocostoclavicularis". The etiology of this disorder is still unclarified. In addition to a swelling that is generally only slightly tender to pressure, the most important symptom is usually a long-standing, intermittent, dull pain in the upper sternum, the claviculae and the adjacent uppermost ribs. Laboratory diagnosis usually shows an accelerated blood sedimentation rate, but other laboratory findings are unremarkable and rheumatological serology gives a negative result. The changes detected by radiography are described, as are the histological findings. Primary or secondary malignant osteomas are also to be taken into account in differential diagnosis. For therapy most authors recommend medicinal treatment with non-steroidal antiphlogistic agents. PMID- 2100511 TI - [Lactation and weaning patterns in Mexico. 1986 National Health Survey]. AB - In the process of nutrition, breastfeeding is fundamentally important, due to the nutritional and immunological value of the mother's milk. Within its beneficial effects, it is found that it improves weight and size in children. Another stage in the child's feeding that should be considered during the first year of life is the weaning that complements, at certain age of the breastfeeder, the nutrition given by breastmilk. The decrease or abandonment of breastfeeding is alarming in the developing countries, where this natural product is more available, economical and nutritious. There is evidence that within the health institutions, artificial feeding is encouraged. The National Health Survey collected basic information on sociodemographic variables risk factors, demand and use of health services. It also included questions on breastfeeding and weaning for the population under one year of age. It was found that 19.9 percent was never breastfed. Another important fact is that 42.4 percent of children received breastmilk for just three months or less. This view suggests that breastfeeding in our country is changing, due to various factors, among which we can mention the differences in life styles, education and economical development among states. The results of this study show interesting data that oblige us to consider more detailed and specific analyses in the future. PMID- 2100512 TI - [The treatment of imported Plasmodium falciparum malaria with halofantrine. Apropos of 59 case reports (corrected and republished article orginally printed in Med Trop (Mars) 1990 Jan-Mar;50(1):113-7)]. AB - 59 cases of Plasmodium falciparum malaria fever occurring in non-immune Caucasian subjects having got a correct chemoprophylaxis by chloroquine were treated by halofantrine (HALFAN). They were given 1500 mg divided in 3 doses of 500 mg every 6 hours from D1 to D8. All them were back from a malarial highly endemic zone with chloroquine resistance. Analysis of the main biological and clinical efficiency parameters displayed very satisfactory results: disappearances of fever (mean 22 H) and parasitemia (mean 36 H) are short. After two months of monitoring, no malaria recrudescence was noted. With an efficacy of 10 p.c. associated to a noticeable clinical and biological tolerance Halofantrine is a first-class treatment of chloroquine resistant malaria fever. PMID- 2100513 TI - Vanadate regulates glucose transporter (Glut-1) expression in NIH3T3 mouse fibroblasts. AB - Vanadate, the major oxidized form of the essential trace element vanadium, has rapid effects on glucose transport in vitro and more delayed effects on glucose transport in vivo. We addressed the question that one potential mechanism for the delayed effects of vanadate on glucose homeostasis could be altered expression of one or more of the genes encoding glucose transporters. To do this we studied vanadate regulation of Glut-1 and Glut-4 in NIH3T3 mouse fibroblasts. Vanadate (5 40 microM) induced cells to proliferate to higher cell densities, and in addition, 40 microM vanadate caused the cells to exhibit a transformed morphology. Glut-1 mRNA was maximally induced 4- to 5-fold over the control value after 6-h exposure to 30 microM vanadate. Unlike the response to serum and growth factors, the vanadate-induced increase in Glut-1 mRNA remained elevated over the control value in the presence of vanadate for 5 days. The vanadate effect was serum dependent and was fully reversible when vanadate was removed from the medium. In the absence of vanadate, the half-life of Glut-1 mRNA was 0.5-1 h, whereas after treatment for 5 h with 30 microM vanadate the half-life was increased to 1.5-2 h. Thus, mRNA stabilization accounts for at least a part of the increase in glucose transporter mRNA levels after vanadate treatment. Glut-4 mRNA was not detected in these cells in either the absence or presence of vanadate. While the importance of this increased Glut-1 gene expression for the vanadate effect on normalization of blood glucose in vivo remains to be determined, an association between vanadate-induced cell proliferation and transformed phenotype, and vanadate-induced Glut-1 mRNA in vitro has been made. Possible potential therapeutic use of vanadate for treatment of diabetes must, therefore, be viewed with caution. PMID- 2100514 TI - In search of a Hoogsteen base paired DNA duplex in aqueous solution. AB - When the oligodeoxynucleotides d(A)6 and d(T)6 are mixed together in a 1:1 ratio (in 100 mM NaCl), the NH signals in the NMR spectrum gave a typical signature of Watson-Crick paired (WC) and Hoogsteen paired (H) AT base pairs. The observation indicates two schemes: Scheme I, WC and H duplexes in slow equilibrium, i.e., WC in equilibrium with H, Scheme II, the WC helix formed is unstable and that it disproportionates into a triple helix (TR) and free d(A)6. We show that (i) addition of extra d(A)6 does not change the helix composition, (ii) addition of a minor-groove specific drug Dst2 (a distamycin analogue) results in an exclusive WC helix-drug duplex, while it does not destabilize triple helix in a 1:2 mixture. In addition we have compared the melting profile, 31P NMR spectra, 1H NMR spectra and the salt dependence of the 1:1 mixture and that of a pure triple helix. All the data from the above experiments overwhelmingly favor Scheme I. However Scheme II cannot be categorically excluded. Based on 1D/2D NMR studies, we have characterized the structural properties of the Hoogsteen double helix in terms of nucleotide conformations. In addition, we computationally demonstrate that the relative stability of the WC over the H duplexes increases with increasing chain length. PMID- 2100515 TI - Four-stranded nucleic acid structures 25 years later: from guanosine gels to telomer DNA. AB - The subject of four-stranded nucleic acid structures is reviewed. Studies on gels formed by guanosine and its analogues have provided appropriate models for the structures of poly(I) and poly(G). The stabilizing influence of certain cations, in particular K+, on Guo-5'-P gels and poly(I) is discussed in the light of recent data on selective K+ stabilization of telomeric DNA structures. The topological possibilities these dG containing sequences could adopt are discussed. In particular the role of the glycosidic linkage (anti/syn), the polarity of the strands and the orientation of the G-tetrad stacks is highlighted. PMID- 2100516 TI - Four-stranded DNA helices: conformational analysis of regular poly(dT).poly(dA).poly(dA).poly(dT) helices with various types of base binding. AB - The paper presents results obtained in conformational analysis of homopolymeric four-stranded poly(dT).poly(dA).poly(dA).poly(dT) DNA helices in which the pairs of strands with identical bases are parallel and have a two-fold symmetry axis. All possible models of base binding to yield a symmetric complex have been considered. The dihedral angles of sugar-phosphate backbones and helix parameters, which are consistent with the minima of conformational energy for four-stranded DNAs, have been determined using the results of optimization of conformational energy calculated at atom-atom approximation. Potential energy is shown to depend on the structure of base complexes and on the mutual orientation of unlike strands. Possible biological functions of four-stranded helices are discussed. PMID- 2100517 TI - Sequence-dependent kinks induced in curved DNA. AB - In certain curved DNA fragments without AA dinucleotides, the gel retardation anomaly associated with curvature passes through a maximum with fragment length, indicating length (and electric field) dependent structural transitions in the DNA. We suggest that thermally induced stereochemical kinks in DNA are stabilized in the gel, thus relieving the effects of curvature. These kinks are shown to occur specifically at CA/TG and TA/TA stacks. Other physical and biological evidence points to frequent structural dislocations at CA and TA steps. These reversible sequence dependent kinks may therefore represent a novel class of structural protein-DNA recognition elements. PMID- 2100518 TI - Local variability and base sequence effects in DNA crystal structures. AB - The importance and usefulness of local doublet parameters in understanding sequence dependent effects has been described for A- and B-DNA oligonucleotide crystal structures. Each of the two sets of local parameters described by us in the NUPARM algorithm, namely the local doublet parameters, calculated with reference to the mean z-axis, and the local helical parameters, calculated with reference to the local helix axis, is sufficient to describe the oligonucleotide structures, with the local helical parameters giving a slightly magnified picture of the variations in the structures. The values of local doublet parameters calculated by NUPARM algorithm are similar to those calculated by NEWHELIX90 program, only if the oligonucleotide fragment is not too distorted. The mean values obtained using all the available data for B-DNA crystals are not significantly different from those obtained when a limited data set is used, consisting only of structures with a data resolution of better than 2.4 A and without any bound drug molecule. Thus the variation observed in the oligonucleotide crystals appears to be independent of the quality of their crystallinity. No strong correlation is seen between any pair of local doublet parameters but the local helical parameters are interrelated by geometric relationships. An interesting feature that emerges from this analysis is that the local rise along the z-axis is highly correlated with the difference in the buckle values of the two basepairs in the doublet, as suggested earlier for the dodecamer structures (Bansal and Bhattacharyya, in Structure & Methods: DNA & RNA, Vol. 3 (Eds., R.H. Sarma and M.H. Sarma), pp. 139-153 (1990)). In fact the local rise values become almost constant for both A- and B-forms, if a correction is applied for the buckling of the basepairs. In B-DNA the AA, AT, TA and GA basepair sequences generally have a smaller local rise (3.25 A) compared to the other sequences (3.4 A) and this seems to be an intrinsic feature of basepair stacking interaction and not related to any other local doublet parameter. The roll angles in B-DNA oligonucleotides have small values (less than +/- 8 degrees), while mean local twist varies from 24 degrees to 45 degrees. The CA/TG doublet sequences show two types of preferred geometries, one with positive roll, small positive slide and reduced twist and another with negative roll, large positive slide and increased twist.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2100520 TI - Electric birefringence of dilute agarose solutions. AB - The technique of transient electric birefringence was used to investigate the orientation of agarose solutions in pulsed electric fields. If the agarose was dissolved in deionized water, the sign of the birefringence was positive when the electric field was small, indicating that the agarose molecules were orienting parallel to the electric field lines. The decay of the birefringence was rapid, consistent with the orientation of individual agarose helices. The amplitude of the birefringence, but not the birefringence decay times, increased as the agarose solution aged, suggesting that the helices formed slowly from the sol state. Increasing the amplitude or duration of the pulsed electric field caused additional negative, and then positive, birefringence signals to appear, characterized by much slower rise and decay times, consistent with the formation of aggregates. The slowest decay times ranged from 7.5-9.0 s, suggesting that the aggregates were several microns in size. When agarose was dissolved in dilute Tris buffer instead of deionized water, the fast positive birefringence signal was not observed, suggesting that individual helices were not present in solutions containing dilute buffer. PMID- 2100519 TI - De novo design of sequences for nucleic acid structural engineering. AB - An interactive procedure has been developed to assign sequences for the design of nucleic acid secondary structure. The primary goal of the procedure is to facilitate macromolecular architecture studies through the design of branched nucleic acid mono- and oligo-junction constructs in a convenient fashion. The essential feature of the sequence-symmetry minimization algorithm employed is the treatment of short sequences as vocabulary elements whose repetition decreases control over the resulting secondary structure. Both manual and semi-automatic application of this approach are available. The design of linear nucleic acid molecules or molecules containing single-stranded loops or connectors is also possible through application of the procedure. PMID- 2100521 TI - Organic osmotic effectors and chromatin structure. AB - Organic amino compounds (taurine, glycine) and polyols (mannitol, sorbitol) are used as osmotic effectors by most animal cells, particularly by some marine invertebrates, but also to a limit extent by mammalian cells. Using physico chemical techniques (circular dichroism, thermal denaturation, solubility, electrophoresis and electric linear dichroism), we demonstrated that some of these effectors prevent chromatin aggregation, without histone release. The influence of glycine on chromatin aggregation, dissociation and reconstitution was thoroughly investigated. Glycine at 2 M concentration does not in itself induce chromatin dissociation; it does hinder salt-induced histone dissociation from chromatin (especially at 1.2 M NaCl) but does not impede chromatin reconstitution. Several hypothesis may be put forward to explain the action of these effectors: (i) a modulation of histone conformation; (ii) a modification of fractional DNA charge, either directly by the zwitterions (glycine, taurine) or indirectly by alteration of cations counterions hydration. The physiological relevance of our experiments is also discussed. PMID- 2100522 TI - Accessibility and structural role of histone domains in chromatin. biophysical and immunochemical studies of progressive digestion with immobilized proteases. AB - The accessibility and role of histone regions in chromatin fibres were investigated using limited proteolysis with enzymes covalently bound to collagen membranes. The changes in chromatin conformation and condensation monitored by various biophysical methods, were correlated to the degradation of the histone proteins revealed by antibodies specific for histones and histone peptides. Upon digestion with trypsin and subtilisin, chromatin undergoes successive structural transitions. The cleavage of the C-terminal domains of H1, H2A and H2B, and of the N-terminal tail of H3 led to a decondensation of chromatin fibres, indicated by increases in electric birefringence and orientational relaxation times. It corresponds to a 15% increase in linear dimensions. The degradation of the other terminal regions of histones H3, H2A and H2B resulted in the appearance of hinge points between nucleosomes without alteration of the overall orientation of polynucleosome chains. Despite the loss of all the basic domains of H1, H3, H2A and H2B, no significant change in DNA-protein interactions occurred, suggesting that most of these protease-accessible regions interact weakly, if at all, with DNA in chromatin. Further proteolysis led to H4 degradation and other additional cleavages of H1, H2B and H3. This caused the relaxation of no more than 8% of the total DNA but resulted in changes in the ability of chromatin to condense at high ionic strength. More extensive digestion resulted in a total unravelling of nucleosomal chains which acquired properties similar to those of H1-depleted chromatin, although the globular part of H1 was still present. The data suggest that histone-histone interactions between H1 and core histone domains play a central role in stabilizing the chromatin fibres, and cuts in H3, H2A and H2B as well as H1, seem necessary for chromatin expansion. On the contrary, H4 might be involved in the stabilization of nucleosomes only. PMID- 2100523 TI - Fluorescence microscopy of the dynamics of supercoiling, folding, and condensation of bacterial chromosomes, induced by acridine orange. AB - The fluorescent dye, acridine orange, was used to visualize bacterial chromosomes extending from bacteria attached to a glass surface. The acridine-induced condensation of these chromosomes was followed in real-time with a low light level video camera. Acridine orange induced the packing of the bacterial chromosome into thick bundles which underwent various forms of condensation, supercoiling, folding, and rolling into a compact particle. Filaments attached to the surface at both ends were topologically constrained and supercoiled rapidly; whereas all three patterns of condensation were noted among filaments attached at only one end or free from the surface. Kinks often appeared in the filaments prior to supercoiling or folding, and the dynamic events observed often occurred around these kinks. These observations identify several mechanisms of condensation available to higher order structures of DNA, and indicate that kinks are an important intermediate step in many of the transitions. PMID- 2100525 TI - Determination of the mineral elements in the pollen of some Gymnospermae. AB - In this work the principal elements (K, Ca, Fe, Mg, Cu, Zn, Mn, Na) constituting the mineral component of the pollen in some Gymnospermae, have been determined. This type of investigation has few matches in literature despite the importance some mineral elements have in germinating the pollen granule. The pollen samples, appropriately treated, were analysed in atomic absorption spectrophotometry and biometrically characterized under the optical microscope. Examination of the analytical data allows verification of the great influence deriving from soil characteristics and, within the families, a specific role of the type. The morphobiometric parameters show that a link exists between small and medium granules and with thin walls and minimum concentration values of Na, Fe, Cu, Zn and Mn. PMID- 2100524 TI - Singlet-singlet energy transfer along the helix of a double-stranded nucleic acid at room temperature. AB - An irreversible electronic energy trap has been formed in calf thymus DNA by methylating about 75% of its G bases at position N-7. This has allowed us to measure for the first time the efficiency of transfer of energy along the helix of a double-stranded nucleic acid at room temperature. It is found that about one out of every three photons absorbed by the other bases is trapped. We have also simulated the data with a stochastic model that uses the dipole-dipole interaction to calculate the efficiency of transfer. In order to approximate the experimental results, the model requires that: (i) the fluorescence quantum yield of T, C, and G in DNA be about 2 x 10(-3), which is about two orders of magnitude larger than the value of the fluorescence quantum yield reported for DNA; and (ii) the fluorescence quantum yield of A in DNA be negligibly small. Requirement (i) is consistent with energy transfer taking place before a very efficient fluorescence quenching process sets in, which could be formation of excited-state complexes (excimers) that do not fluoresce appreciably. Requirement (ii) implies a very short fluorescence lifetime for A, which is consistent with the reported absence of a significant number of photoproducts formed by A in DNA. The simulations find that, on the average, the excitation energy takes about 1.2 steps to reach the trap; that is to say, bases that are nearest and next nearest neighbors of the trap are, in effect, the only energy donors. Both intra- as well as interstrand energy transfer (the latter only for the C-trap base pair) make significant contributions. The value of the efficiency for pairwise base-base intrastrand transfer is about 60%, whereas those for base-trap intra- and interstand transfer are 90% and 80%, respectively. The corresponding values for the rate constant of transfer are 2 x 10(11), 1 x 10(12), and 4 x 10(11) s-1. Transfer is inefficient when A is the donor or the acceptor. In addition to the dipole-dipole term, the only other significant term in the expansion of the interaction potential is the dipole-quadrupole term which, however, makes only a small contribution to the overall transfer efficiency. The electron exchange interaction appears to be much less efficient than the coulombic interaction. PMID- 2100526 TI - Evaluation of the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing. AB - To evaluate the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing, three groups of women were studied by computerized bone densitometry at the radius mid-point and at the distal point, modified according to the Abwrey technique. All women were in apparent good health and never had estrogen therapy. In the first group there were 64 women aged between 30 and 50 who were ovariectomized between 25 and 35 years of age. The second group was made up of 309 women between 50 and 55 years. In the third group there were 136 women aged 30-50 with normal ovaric function. The ordinary functions of linear polynomial regression were used to describe the variations in density with age. The percentage of postmenopausal bone loss was determined by calculating the BMC value at the start of the menopause and again twenty years later, according to the linear regression equation of postmenopausal period of each group of women in the study. The women who had natural menopause showed an average bone loss per year of 1.63% at the mid radius and 1.0% at the distal point. The ovariectomized women had an average loss of 0.85% at the mid point and 0.66% at the distal point. No significant decrease of bone mass was found before menopause. From a comparison between the two groups of women with analogous periods of menopause, it comes out that, during the first 20 years of natural menopause, estrogen deficiency is responsible for 52.5%-66.4% of the bone mineral loss, the remaining amount being attributable to other causes, connected with ageing. Estrogen deficiency is therefore, the principal factor causing bone mineral loss in natural menopause. PMID- 2100527 TI - [Arterial hypertension caused by low renin: comparison of the calcium antagonist nifedipine and the ACE-inhibitor enalapril as to antihypertensive efficacy]. AB - The aim of this study was to compare the clinical effects of calcium-entry blocker Nifedipine and ACE-inhibitor Enalapril in hypertensive patients with glucose intolerance that have lower plasma renin activity. A blood sample for basal PRA was obtained from 21 subjects; then, 11 patients received Nifedipine (20 mg. b.i.d.) and 10 Enalapril (20 mg. q.d.). The extent of blood pressure fall after 12 weeks of treatment was inversely related to basal PRA levels in Nifedipine treated group only; however, the hypotensive effect of both drugs was comparable. PMID- 2100528 TI - [In vitro dissection and development of sheep embryos after preservation at very low temperature (-196 degrees C)]. AB - Embryos obtained from Sardinian breed ewes superovulated with FSH-p (Sigma) were frozen at -196 degrees C in liquid nitrogen. After 6 months storage, the embryos (12, all at the compact morula stage), were thawed in a water bath at 39 degrees C for 30 minutes. Six embryos were dissected with a Leitz micromanipulator using a simplified technique. Both demi and intact embryos, were cultured in medium TCM 199 + 10% FCS at 38 degrees C in 5% CO2 for 24 hours. Only five demi-embryos (41.6%) became blastocysts versus 4 whole embryos (66.6%) after the culture period. Splitting as our results show, lowers the embryo viability after freezing thawing, but it can be used in certain instances to obtain genetic improvement in the Sardinian breed. PMID- 2100529 TI - [In vitro separation and development of sheep blastomeres]. AB - Four cell embryos collected by laparatomy from Sardinian breed ewes superovulated with FSH-p (16 mg Sigma), were divested of their zonae pellucidae (ZP) by micromanipulation or chemical methods (pronase 0.5%, tyrode pH 2.2). The blastomeres were separated by pipetting using a flame polished pasteur pipette in a Ca free medium (PBS. Sigma) and were inserted into previously evacuated Z.P. using a Leitz micromanipulator. The Z.P. were removed either mechanically or with acid tyrode; pronase was unable to digest them after incubation at 30 degrees C for 120 minutes. The single blastomeres were cocultured on a monolayer of ovine oviductal epithelial cells in TCM 199 + 10 FCS at 38 degrees C in 5% CO2 for 60 hours. No developments were observed in blastomeres obtained by acid digestion of the ZP while 50% of the other blastomeres continued their development until the 16 cell stages. Our results suggest that coculture with oviductal epithelial cell monolayers can support in vitro development of single ovine blastomeres. PMID- 2100530 TI - Studies on heterocyclic compounds: spiro [indole-3,2'-thiazolidine] derivatives. Antimicrobial activity of monohalogenated 3'-phenylspiro 3H-indole-3,2' thiazolidine-2,4' (1H)-diones. AB - The following halogenated 3'-phenyl [3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione of general formula (A) were synthesized and screened for antimicrobial activity. (formula: see text) where: X = H (I, III, V, VII, IX, XI, XIII, XV), CH3 (II, IV, VI, VIII, X, XII, XIV, XVI); Y = H (I, II), 3-F (III, IV), 2-Cl (V, VI), 3-Cl (VII, VIII), 4-Cl (IX, X), 2-Br (XI, XII), 3-Br (XIII, XIV), 4-Br (XV, XVI). The synthetic approach involves the preparation of variously substituted Schiff-bases of indol-2,3-dione, which then are subjected to cyclocondensation with alpha mercaptoalkanoic acids, to give spirothiazolidinones of type (A). The prepared compounds were screened against S. aureus, B. cereus, M. paratuberculosis, E. coli, S. typhi, Pr. mirabilis, Ps. aeruginosa, C. albicans, S. cerevisiae, A. niger by a disk-diffusion assay (Kirby-Bauer modified. The results of the antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. 3 Fluoro-derivative (III) showed inhibitory activity especially toward S. aureus and C. albicans. Chloroderivatives (VII) and (VIII) showed broad-spectrum "in vitro" antimicrobial activity, and were especially inhibitory toward S. aureus, E. coli, and S. Typhi. Fluoro-derivative (IV) and bromo-derivatives (XIII) and (XIV) possessed marked antimicrobial activity against M. paratuberculosis. PMID- 2100531 TI - Studies on heterocyclic compounds: spiro [indole-3,2'-thiazolidine] derivatives. II. Antimicrobial activity of halogenated 3'-phenylspiro 3H-indole-3,2' thiazolidine -2,4 (1H)-diones. AB - The following polyhalogenated 3'-phenyl 3H-indole-3,2'-thiazolidine -2,4' (1H) dione of general formula (A) were synthesized and screened for antimicrobial activity. (formula: see text) where: X = H (I, III, V, VII, IX, XI), CH3 (II, IV, VI, VIII, X, XII); Y = H (I, II), 2,4-F2 (III, IV), 2,4-Cl2 (V, VI), 3,4-Cl2 (VII, VIII), 2,6-Cl2 (IX, X), 2,4,6-Cl3 (XI, XII). The general synthetic route involves the preparation of variously substituted isatin-3-imines, which are subjected to cyclocondensation with thioglycolic acid to give compounds I, III, V, VII, IX, XI, or thiolactic acid to give compounds II, IV, VI, VII, X, XII. The prepared compounds were screened against S. aureus, B. cereus, M. paratuberculosis, E. coli, Pr. mirabilis, Ps. aeruginosa, C. albicans, S. cerevisiae, A. niger by a disk-diffusion assay (Kirby-Bauer modified). The results of the antimicrobial screening showed that the polyhalogenated derivatives of type (A) exhibited varying degrees of activity against Gram positive, Gram-negative bacteria, and fungi. Compound (III) showed a significant activity toward A. niger, moreover compound (IV) was active toward C. albicans. Compound (IX) was very active toward S. typhi and Ps. aeruginosa. Compounds (VII), (IX) and (XII) were very active toward M. paratuberculosis. PMID- 2100532 TI - [Ultrastructural study of the yeast-mycelium transition in Histoplasma capsulatum. II. Changes at 34 degrees C]. AB - The ultrastructural changes which occur during the mycelium to yeast transition in Histoplasma capsulatum induced by a temperature shift from 25 degrees C to 34 degrees C are described and compared to those observed after a temperature shift from 25 degrees C to 37 degrees C. 24 hours after the temperature shift to 34 degrees C only 8% of the cells are lysed. However, many mitochondria have lost their characteristic elongated form and have become rounded. Vesicular cristae which are no longer oriented parallel to the long axis of the mitochondria are also observed. In contrast a temperature shift from 25 degrees C to 37 degrees C induces lysis of 70% of the cells; mitochondria are rarely observed in the remaining cells. These ultrastructural changes can be correlated with the uncoupling of oxidative phosphorylation and the production of heat shock proteins. PMID- 2100533 TI - [Behavior of various enzyme activities during high blood lactate and pyruvate levels in albino rats reared in a normobaric hypoxic atmosphere for 1 or 2 generations]. AB - Albino rats Wistar family raised in normobaric hypoxic environment (10% O2 in N2) since one or two generations showed an increase in arterial blood creatine kinase, glutamate-dehydrogenase, lactic-dehydrogenase, lactate and pyruvate when compared with normoxic controls. Moreover the values found in hypoxic rats of second generation were intermediate between those found in hypoxic rats of first generation and normoxic controls. These differences are probably due to an improved efficiency of the processes of cellular adaptation to the hypoxic environment when named species remain in hypoxic environment for more than one generation. PMID- 2100534 TI - [Further characterization of the orange carotenoid protein extracted from the marine demosponge Axinella verrucosa]. AB - The orange coloration of the marine sponge A. verrucosa is provided by some carotenoids widespread in the ectosome and mesohyl of this sponge. These carotenoids are bound to a glyco(lipo)protein forming a non covalent complex. Six carotenoids are bound to the glyco(lipo)protein, but only alpha-carotene was identified by HPLC. The aminoacid composition is quite different from those previously reported in Porifera. The content of Ser and Gly and the total polar residues are high. The presence of Met and Pro was not evidenced. Some unusual aminoacids were detected, of which only Taurine was probably identified. PMID- 2100535 TI - [Microanatomical relationships of the anterior inferior cerebellar artery and the facial nerve]. AB - The microanatomical relationships between facial nerve and anterior inferior cerebellar artery were examined in 30 adult cadavers. Seventeen of the 60 arteries were situated ventrally to the facial nerve; 8 dorsally to the facial nerve root; 26 passed between the seventh and eighth cranial nerves; 9 round the seventh and eighth cranial nerves. Forty-one of the 60 nerves were in contact with the arteries. The significance of microanatomical relationships between the anterior inferior cerebellar artery and the facial nerve was discussed. PMID- 2100536 TI - [Electroneurography and other electric tests on prognostic assessment of Bell's palsy]. AB - Twenty-two patients with Bell's palsy who had complete unilateral facial paralysis were selected for this study. Electroneurography (ENoG), nerve excitability test (NET), maximal stimulation test and facial nerve latency test were done on each patient. The patients were examined within 21 days of onset of facial paralysis and evaluated at least six months after onset to determine the degree of recovery of facial motor function. ENoG was the most accurate test for prognostic assessment of Bell's palsy when it was performed within 3 weeks after onset. When the response loss of ENoG on the involved side was 90% or less of that on the normal side, 83.3% of the patients had complete recovery of facial function, however, when loss was more than 90%, there was 70% chance for incomplete recovery. NET is a relatively accurate test, perhaps, it should be recommended because it is inexpensive and easy to manipulate. PMID- 2100537 TI - [Decompression of geniculate ganglion of facial nerve]. AB - Decompression of geniculate ganglion of facial nerve in 20 cases of facial palsy caused by temporal bone fracture, herpes zoster otitic and Bell's palsy was reported. Sixteen cases had been followed up for half to four years. Complete recovery was observed in 13 cases and partial recovery in 3 cases. Transmastoid attical approach was used. The geniculate ganglion and the distal part of the labyrinthine segment of the facial nerve could be exposed by this approach. The authors emphasized the importance of decompression of the geniculate ganglion, because of the anatomic characteristics and the pathologic features. The indications, the surgical approach and the precautions during operation were discussed. PMID- 2100538 TI - [Damage to cochleae in newborn guinea pigs by 80dB white noise]. AB - Two groups of guinea pigs (the newborn and the adult) were exposed to 80dB SPL white noise for 72 hours. The effects were observed with E CochG, surface preparation, scanning electron microscopy and histochemical techniques. The results showed that: 1. the response threshold of the newborn was elevated after exposure; 2. the rate of OHC loss was higher in cochleas of the newborn than those of the adult; 3. OHC damage was mainly found in the fourth turn of cochlea of the newborn; 4. the LDH activity decreased in the newborn. It seems that the white noise could damage the hair cell function and structure in the newborn guinea pigs which are more susceptible to noise than the adult ones. The different susceptibility might be related to the degree of development and maturity of the cochleas. PMID- 2100539 TI - [Saccadic sinusoidal tracking test]. AB - This paper introduces a new method of ENG-Saccadic sinusoidal tracking test (SSTT). In 4 of the 55 cases with peripheral vestibular lesions, the results were abnormal. But among 50 cases with central lesions, 40 cases were abnormal. In 50 control cases, no abnormalities were found. The results showed that SSTT might be of great value in differential diagnosis of central Lesions. PMID- 2100540 TI - [A simple useful rhinoresistometer: mechanical principle and clinical applications]. AB - A new rhinoresistometer consisting of a pressure nozzle, a flow nozzle, a two-U tube manometer and a X-Y chart recorder is introduced in this paper. Such an apparatus is simple in construction and easy to use. The expiratory transnasal pressure difference is measured by a U-tube manometer while the nasal airflow is measured by flowmeter. With this apparatus, the subject's nasal airway resistance can be evaluated accurately and the nasal airway resistance curves drawn automatically. The mechanical principle of the apparatus is described and the nasal airway resistances of 200 normal subjects are reported in this article. PMID- 2100541 TI - [Histopathological studies on glottic cancer by serial sections]. AB - In 31 glottic cancer specimens from partial laryngectomy, the histopathological findings were compared with vocal cord motility and 5-year survival rate. Among the 31 cases, 7 had ventricular involvements, in which 3 were transglottic tumors; 2 had had their framework destroyed. Eight cases had anterior commissure involvement. Only one had the tendon affected. Of 20 cases with mobile cords, the lesions were entirely superficial to the conus elasticus. Only a few specimens showed minimal invasions of the arytenoid region. Of 8 cases with limited vocal cord motility, invasion of the thyroarytenoid muscle was quite apparent, 4 specimens had the arytenoid areas surrounded by nests of tumor cells, and one case had local recurrence 12 months after operation. There were 3 cases with vocal cord fixation, 2 with subglottic extensions showed cricoid cartilage involvement and had had recurrences 10 and 12 months after operation. Another one with transglottic lesion was controlled by middle portion subtotal laryngectomy. Nine cases had subglottic involvement. One with transglottic lesion had recurrence, the other with arytenoid invasion had local recurrence. In two more recurrent cases, tumors cells spreaded submucosally toward the infraglottic area. PMID- 2100542 TI - [Treatment of hereditary angioedema]. AB - Hereditary angioedema is a rare familial disease caused by the defect of complement C1esterase inhibitor (C1-INH). It is characterized by recurrent acute edema of the extremities, the face, the respiratory tract and the gastrointestinal tract. Acute laryngeal edema usually produces laryngeal obstruction. Two cases have been treated since 1986, one of them had been admitted for forty-five times because of recurrent acute laryngeal edema. Investigations showed two families with a high incidence of this disease. Laboratory examination showed a remarkable decrease of C1-INH and C4. Tracheotomy is indicated in patients with laryngeal edema. Great success was achieved in two patients treated with danazol. PMID- 2100543 TI - [Advances in the research on Bell's palsy]. PMID- 2100545 TI - Abstracts for the 13th annual meeting of the Japanese Society for Investigative Dermatology. July 21-23, 1988, Fukuoka, Japan. PMID- 2100544 TI - The effect of cyclosporin A on proliferation and differentiation-associated antigens of normal human skin xenografted onto nude mice. AB - Cyclosporin A (CsA) has been shown to inhibit, in vitro, the proliferation of cultured normal and neoplastic keratinocytes and to exert also in vivo an antiproliferative effect on keratinocytes of normal human skin xenografted onto nude mice. To gain further insight into the effects of CsA on human skin we investigated the immunohistochemical expression of several epidermal proliferation- and differentiation-associated antigens in the same model: six week-old nude mice received a xenograft of full-thickness normal human skin; six animals subsequently received a daily subcutaneous injection of 50 mg/kg of CsA diluted in olive-oil while the others received an equivalent volume of olive-oil. The rate of epidermal proliferation was evaluated through a BrdU pulse-labelling technique, and was found to be decreased by 56% in the CsA-treated epidermal xenografts as compared to the controls. The xenografts were further examined for the expression of the following antigens: Epidermal Growth Factor- and Transferrin-receptors, Ki-67, 56.5 kD keratin polypeptide, Filaggrin, Involucrin, beta 2-microglobulin, Ulex Europaeus I- and Peanut-Agglutinin-binding sites. Most of these antigens were unchanged on CsA-treated human xenografts. However, the 56.5 kD keratin polypeptide which was consistently expressed by both basal and suprabasal epidermal keratinocytes in control xenografts showed a normal expression pattern (i.e. suprabasal keratinocytes only) in three out of the six CsA-treated xenografts. These results raise the possibility that, concurrently with a cytostatic effect, CsA may also affect keratinocyte differentiation and that this effect, possibly contributes in the beneficial effect of CsA in diseases of abnormal keratinization. PMID- 2100546 TI - The role of ligand-receptor interactions in disease. AB - Ligand-receptor interactions play a determining role in many cell biological interactions. Mutations of ligands or receptors can both cause a disturbance in these interactions. In this paper an example will be given of these types of defects. Finally it will be speculated which role receptor mechanisms may play in the field of dermatology. PMID- 2100547 TI - Papillary eccrine adenoma. Immunohistochemical and ultrastructural analyses. AB - A case of papillary eccrine adenoma was analysed with immunohistochemical and ultrastructural methods regarding their direction of differentiation. It was found that the majority of the structures show either eccrine ductal or glandular differentiation. There were some segments, particularly in those exhibiting papillary growth, where cells similar to eccrine secretory (clear) cells or cells with characteristics of both ductal basal cells and glandular myoepithelial cells were present. PMID- 2100548 TI - Change in sphingomyelinase activity in human epidermis during aging. AB - We have investigated the change in activity of sphingomyelinase in human whole epidermis during aging. The sphingomyelinase activity gradually decreased with the aging process; that of people aged eighty decreased to one fourth of that of people aged twenty in same area. This result indicates that the lipid metabolism may be altered in the epidermis during aging. PMID- 2100550 TI - Enzyme-linked heterogeneous immunoassays with electrochemical detection. PMID- 2100549 TI - Risk factors for squamous cell carcinoma of the skin in Saskatchewan, Canada. AB - Completed questionnaires regarding suspected risk factors for skin cancer were completed by 178 cases of SCC of the skin in Saskatchewan, Canada, and 284 age- sex- and location-matched controls. Significant risk factors identified using chi2 analyses were: farming, family history of skin cancer, light eye color, blond or red hair color, skin types I or II, obvious freckles in childhood, history of severe sunburn, and the use of the herbicide 2,4-Dichlorophenoxy acetic acid. The following relative risks were identified: (1) All cases of SCC of the skin and matched controls: agricultural occupation 1.49, history of severe sunburn 1.49. (2) All men with SCC of the skin and matched controls: history of severe sunburn 1.36 (3) All women with SCC of the skin and matched controls: agricultural occupation 1.83, and skin types I or II 1.48. No association was noted on our study between a history of psoriasis and development of SCC. Neither was an association between smoking and SCC found. PMID- 2100551 TI - Novel detection system for homogeneous enzyme immunoassays. PMID- 2100552 TI - Some statistical methods for immunodiagnostic cancer tests. AB - This paper complements an article in the previous edition of this book by emphasizing recent development in the use of ROC curves, the analysis of multiple markers, and methods of analysis for serial marker data. What has not changed is the need for statisticians and clinicians to work together closely to define clinical issues and their statistical formulations. PMID- 2100553 TI - Rapid response fiber optic evanescent wave immunosensors. PMID- 2100554 TI - Recent advances in flow cytometric techniques for cancer detection and prognosis. AB - The application of flow cytometry to cancer diagnosis and the prediction of tumor behavior continues to expand. The ability of flow cytometry to examine multiple parameters of large numbers of individual cells is being exploited increasingly to characterize neoplastic processes better. This will allow closer examination of tumor heterogeneity and identification of subpopulations with different behavioral patterns. Flow cytometry is being used with greater frequency in attempts to predict tumor behavior and response to therapy. Flow cytometry may have the most to offer in this area. Diagnosis of cancer by routine histopathological examination will not be replaced by flow cytometry; flow cytometry will be used in conjunction with morphological descriptions. The detection of proliferation antigens and oncogene products, as well as cell cycling, provides information on neoplastic progression that is not readily obtainable by other methods. In addition, flow cytometry will undoubtedly be used to measure other features of neoplastic cells, such as enzyme levels and ion fluxes, which may better characterize the behavior of the tumor. Advances in flow cytometry instrumentation, light sources, fluorochrome development, and basic aspects of cellular and molecular biology will continue to permit this technology to define neoplastic cells and their behavior better, resulting in both improved patient care and a better understanding of tumor biology. PMID- 2100555 TI - Use of monoclonal antibodies as probes for oncogene products. PMID- 2100556 TI - Use of immunologic techniques in gene analysis. PMID- 2100557 TI - Breast epithelial antigens in the circulation of breast cancer patients. PMID- 2100558 TI - Lymphocytic leukemia and lymphomas. PMID- 2100559 TI - Immunodiagnosis of acute nonlymphocytic leukemia. PMID- 2100560 TI - Multivariate techniques to assess laboratory tests in cancer patients. AB - In this chapter the application of multivariate techniques for the assessment of laboratory tests in cancer patients has been reviewed. We emphasize that the transformation of laboratory test values into just two categories (normal or abnormal) may entail a considerable loss of information. For instance, correlation between two laboratory tests that may be important for differentiating among various clinical categories of patients may disappear when this procedure is used. When only a single set of laboratory results measured in the same specimen is available for a given patient, we must compare these values to those obtained from other patients or healthy subjects to make inferences about the patient on the basis of the laboratory results. Thus, the analysis of the data must be group based. Discriminant analysis, logistic regression analysis, and survival analysis based on Cox's regression model are the techniques most often used in this situation. By contrast, when previous results are available from the same patient we may compare his or her present values to those previously obtained when we want to make inferences about the patient. Our objective is to make a prediction about the time that will elapse until some specified event (death or recurrence of disease) occurs. Two models that have been applied in this situation--the Markov chain and the autoregressive time series model--were reviewed and examples of specific medical applications presented. PMID- 2100561 TI - Serum tumor markers for pancreatic carcinoma. AB - Various biochemical substances are being evaluated for use as serum tumor markers of adenocarcinoma of the pancreas. The currently established markers, CA 19-9 and POA, have an important but limited role in the diagnosis of pancreatic carcinoma. The role could be expanded if the specificity of these tests for pancreatic cancer could be increased, and this may be possible for each of these tests if several recent findings can be confirmed. Most of the new tumor markers are blood group-related substances, in that the cancer-associated substances share epitopes that are similar to those of the Lewis blood group system. It seems likely that a "panel" of these markers could improve the specificity of these tests for pancreatic carcinoma. However, improvement of the clinical specificity appears unlikely since each of these markers has a high false-positive rate in patients with other cancers, liver diseases, and nonmalignant diseases of the pancreas. Additional study will be required to determine the optimal group of these tests to be used as a pancreatic cancer test panel. Also, more emphasis should be directed to the identification of tumor markers that can be used to detect pancreatic cancer at a stage when it can be treated effectively. The use of tumor markers for monitoring patients does not result in longer patient survival times or a higher survival rate because salvage therapies for this disease are ineffective. If effective salvage therapies can be developed, monitoring with serum tumor markers will become more significant. Thus, continued emphasis should be given to the development of serum tumor markers that have diagnostic utility. PMID- 2100562 TI - Melanoma: the development of immunoconjugates from a preclinical viewpoint. PMID- 2100563 TI - Predictive value of immunodiagnostic cancer tests. PMID- 2100564 TI - Immunodiagnosis of cancer. PMID- 2100565 TI - Markers of central nervous system tumors. PMID- 2100566 TI - Immunodiagnosis of ovarian tumors. PMID- 2100568 TI - Uterine tumors. PMID- 2100567 TI - Tumor markers of head and neck carcinoma. AB - Evaluation of the various tumor markers that have been studied in patients with SCC of the head and neck reveals no single marker or battery of markers that is sufficiently specific or sensitive to provide useful clinical data in the treatment of patients with these cancers. This finding reinforces previous investigative and clinical impressions that would suggest that carcinoma of the head and neck is a heterogeneous entity. These tumor marker studies provide additional support for the hypothesis that although various carcinomas of the head and neck may appear identical microscopically, their behavior both clinically and biochemically is nevertheless heterogeneous. Due to the wide variability of the behavior of these tumors, the search for the perfect tumor marker continues. The development of additional multiple-marker batteries may provide the closest approximation to a perfect marker that is feasible. Additional studies into the nature and function of oncogenes may provide additional clues to the variability of these tumors and the resultant heterogenicity of their marker expression. PMID- 2100569 TI - Use of multiple markers to enhance clinical utility. PMID- 2100571 TI - Thyroid tumors. PMID- 2100572 TI - Immunodiagnosis of renal cell carcinoma. AB - Development of immunoassays for the diagnosis of RCC offers significant promise of improved clinical treatment of this disease. While this promise remains to be fulfilled, there is reason to believe that advances will soon be forthcoming. MABs have defined numerous kidney-associated antigens. In at least one instance (ADAbp), an immunoassay has already been established that aids in the diagnosis of benign renal diseases. A similar approach may also be useful in renal cancer. Likewise, in at least one instance a previously undefined peptide (the HHM factor) has been closed and sequenced. Synthesis of this peptide and production of antibodies to it cannot be far off. Measurement of this peptide and/or of the many other aberrantly produced peptides associated with this cancer may be anticipated to improve substantially our ability to diagnose early and, therefore, cure renal cancer. PMID- 2100570 TI - Bone tumors. PMID- 2100573 TI - Immunoglobulins in diagnosis and monitoring of neoplasia. PMID- 2100574 TI - Serum and tissue banks for biological markers. PMID- 2100575 TI - Serum isoenzymes in cancer diagnosis and management. AB - The 10 isoenzyme markers discussed here represent those that in the author's judgment show promise as effective tumor markers. The relative usefulness of these isoenzymes as tumor markers is summarized in Table 6. Each isoenzyme is evaluated by a rating system, with a scale of 0-5 points in each of seven categories. The hypothetical ideal tumor marker received 5 points in all seven categories for a total score of 35. Unfortunately, less than perfect scores ranging from 9 to 26 were found for the 10 isoenzymes evaluated here. The five best isoenzymes were neuron-specific enolase (26 points), prostatic acid phosphatase (23 points), placental alkaline phosphatase (20 points), thymidine kinase 1 (16 points), and lactate dehydrogenase 1 (16 points). In general, low isoenzyme scores can be attributed to the problems exhibited by all tumor markers: insensitivity to early-stage malignancies and false-positive elevations in nonmalignant diseases. Nevertheless, each of the 10 isoenzymes described here has potential clinical usefulness to support a diagnosis of cancer and/or to assist in the monitoring of therapy. PMID- 2100576 TI - Mucin glycoproteins as tumor markers. AB - Extensive biochemical studies have shown that mucin tumor antigens have a range of molecular sizes from 200 to greater than 1000 kDa. The molecular size of mucin antigens can be dramatically affected by the source and method of purification. Mucin antigens vary from 24 to 80% in carbohydrate content and their density is usually greater than 1.40 g/ml. Galactose and N-acetyl glucosamine are the predominant sugar residues in many mucins, whereas mannose is usually present in low levels or absent. The amino acids serine, threonine, alanine, glycine, and proline are abundant in mucins. An O-glycosidic linkage between the carbohydrate and protein of mucins is the most common linkage encountered. The gene encoding the core peptide for at least one mucin tumor marker, HMFG, has been identified, sequenced, and expressed. These findings may lead to a better understanding of the multiepitope nature of mucin tumor markers. The advent of hybridoma technology has yielded several monoclonal antibodies that have been used to identify the presence of tumor-associated mucins in the sera of cancer patients. Elevated levels of mucin antigens have been found in the serum of most patients with advanced adenocarcinomas. Many studies have shown that tumor-associated markers are useful in monitoring patients following cancer treatment. Clinically useful immunoassays have been developed for monitoring patients with ovarian, breast, and pancreatic adenocarcinomas. Although individual mucin tumor markers show limited utility in detecting early adenocarcinoma, recent studies using multiple mucin markers have suggested that early detection, at sensitivities greater than 50%, can be achieved. PMID- 2100578 TI - Reactivity of chloronitrobenzenes towards glutathione under physiological conditions: the relationship between structure and reaction rate. PMID- 2100577 TI - Reductions in sample pretreatment requirements by using high-performance capillary electrokinetic separation methods. PMID- 2100579 TI - Purification of aldehyde oxidase from liver by affinity chromatography and FPLC. PMID- 2100580 TI - Automatic on-line extraction coupled with electrochemical detection as an improved method for the HPLC co-analysis of codeine and morphine in plasma and gastric juice. PMID- 2100581 TI - Bio-analysis of N-(deacetyl-O-4-vinblastoyl-23)-L-ethyl isoleucinate, methane sulphonate (VileE) by high-performance liquid chromatography with fluorescence detection. PMID- 2100582 TI - Ultra-sensitive coupled-column liquid chromatographic determination of retinoids by direct injection of large plasma volumes and ultraviolet detection. PMID- 2100584 TI - Automated high-performance liquid chromatographic assay for Trapidil in human plasma. PMID- 2100583 TI - Analysis of urinary and plasma catecholamines using a single LC-EC system. PMID- 2100585 TI - Automation of a high-performance liquid chromatographic assay for the determination of nicotine, cotinine and 3-hydroxycotinine in human urine. PMID- 2100586 TI - The analysis of atenolol in plasma using an automated sample preparation technique. PMID- 2100587 TI - Liquid chromatographic determination of mianserin in plasma by fluorescence detection after on-line photochemical reaction. PMID- 2100588 TI - Determination of gangliosides in parenteral dosage form by high-performance liquid chromatography. PMID- 2100589 TI - Determination of bamifylline hydrochloride impurities in bulk material and pharmaceutical forms using liquid chromatography with ultraviolet detection. PMID- 2100590 TI - Dependence of the retention of pyrazolidine-3,5-diones on eluent pH in reversed phase high-performance liquid chromatography. PMID- 2100591 TI - The analytical profile of rufloxacin, a new fluoroquinolone, by reversed-phase high-performance liquid chromatography. PMID- 2100592 TI - Background noise reduction in post-column continuous-flow analysis combined with RPLC and computer-aided detection for the characterization of peptides. PMID- 2100593 TI - A sensitive high-performance liquid chromatographic method for the assessment of percutaneous absorption of topical corticosteroids. PMID- 2100594 TI - Thin-layer chromatography for detection of aromatic acids in urine after occupational exposure to aromatic compounds. PMID- 2100595 TI - The detection of [14C]propranolol following supercritical fluid chromatography using in-line radioactivity detection. PMID- 2100596 TI - A practical approach to method validation in pharmaceutical analysis. AB - Guidelines issued by Regulatory Authorities make it clear that validation of analytical methodology is now widely required in support of registration dossiers. Although some attempts are made at defining terms and some vague indications are sometimes provided within these guidelines, no clear advice is provided on how validations should be conducted and what results should be expected. In this paper it is attempted to suggest some practical approaches to conducting validation and in particular to the determination of accuracy, linearity and limit of detection/quantitation. PMID- 2100597 TI - Chromatographic system suitability tests--what should we be using? AB - System suitability tests are applied to chromatographic analytical methods to confirm the methods' continuing suitability for use on different occasions following their initial validation. The paper discusses the checks and controls which have traditionally been applied, questions their appropriateness and makes recommendations for others that should be considered. PMID- 2100598 TI - Evaluation of criteria for the acceptance of bioanalytical data. AB - Results from bioanalytical analyses for registration of a new drug entity are used to define its pharmacokinetics and bioavailability/bioequivalence. Whilst analytical data may be derived from the application of a validated method, it is essential to apply mathematical criteria to its acceptance, in order that the analyst can be assured that the assay is performing within defined limits and to its validated specification. Parameters evaluated for acceptability are the batch calibration curve, the minimum quantifiable concentration and the quality control (QC) sample acceptability. Specifically, six QC samples per analytical batch are used, two samples at each of three concentrations. The rationale for the definition of these criteria is evaluated together with a consideration of their applications and limitations. The relevance and use of Shewhart and Cusum plots to monitor assay performance is illustrated. PMID- 2100599 TI - Method validation in the bioanalytical laboratory. AB - Bioanalytical methods, based on a variety of physico-chemical and biological techniques such as chromatography, immunoassay and mass spectrometry, must be validated prior to and during use to engender confidence in the results generated. The fundamental criteria for assessing the reliability and overall performance of a bioanalytical method are: the evaluation of drug and analyte stability, selectivity, limits of quantification and detection, accuracy, precision, linearity and recovery. The extent to which a method is validated is dependent on its prospective use, the number of samples to be assayed and the use to which the data are put. Specific analytical techniques may require additional validation such as antibody-binding characteristics, peak purity determination, evaluation of matrix effects or structural confirmation of the analyte. Ideally each assay should be cross-validated with a method utilizing a highly specific detector such as a mass spectrometer. Once in use, the performance of the method should be monitored using quality control standards. If a method is set up in another laboratory, the performance of that assay should be monitored with quality control standards sent from the originating laboratory. PMID- 2100600 TI - Screening chemical and physical stability of drug substances. AB - General multistep methods are described for the screening of the chemical and the physical stability and/or reactivity of new drug candidates. The chemical reactivity is studied in aqueous buffer solutions; the rate of degradation is measured as a function of pH. The products of the reaction mixture are evaluated at selected pH-values as a function of time and key reaction products are identified. Strategies for testing degradation products in stability studies are discussed. The purpose of the physical reactivity test is to obtain information on the existing solid-state form in relation to the thermodynamically stable form. A method for finding the stable form is described. When polymorphism is observed a search for additional polymorphs is performed and the different solid phases are characterized. Special tests are described for hydrates and anhydrous forms. PMID- 2100601 TI - Application of solid-phase extraction to the isolation and determination of paracetamol and its metabolites. AB - A series of clean-up columns for solid-phase extraction (SPE) were packed with various C18 phases of different physico-chemical surface properties. These SPE columns were used for the isolation and determination of paracetamol and its metabolites from biological samples. The packing with a monomeric structure of chemically bonded phase showed the best recovery of tested substances in urine. PMID- 2100602 TI - Indirect continuous automatic determination of pharmaceuticals by atomic absorption spectroscopy. AB - The implementation of continuous separation techniques such as precipitation, liquid-liquid and solid-liquid extraction in FIA manifolds coupled on-line with an atomic absorption spectrometer for the determination of active components (sulphonamides, local anaesthetics, amphetamines, benzodiazepines, chloramphenicol and methadone) in pharmaceuticals and biological fluids is systematically described. The basic features of the analytical methodologies described (sensitivity, selectivity, precision and rapidity) are also discussed and critically compared. PMID- 2100603 TI - Spectrophotometric determination of adrenaline with an oxidative column in a FIA assembly. AB - A single channel FIA assembly is proposed for the spectrophotometric determination of adrenaline, the aqueous sample solution is directly injected into the carrier stream leading the sample through a manganese dioxide column at 80 degrees C, and on to the spectrophotometer flow-cell. The calibration graph is linear up to 17 ppm of adrenaline. The influence of other substances has been studied and the method has been applied to the determination of adrenaline in a pharmaceutical formulation. PMID- 2100604 TI - FIA-fluorimetric determination of thiamine. AB - A flow injection-fluorimetric determination of thiamine is reported. The procedure is based on the oxidation of the analyte with potassium hexacyanoferrate(III) immobilized on an anionic exchange resin; the fluorescence is monitored in aqueous basic solution. Concentrations of the vitamin of 0.1-4 ppm have been determined; the relative standard deviation was 1.8%. The injection rate was 28 samples/h. The influence of other substances and the determination of the drug in a pharmaceutical formulation are also reported. PMID- 2100605 TI - Inclusion complexation of doxorubicin and daunorubicin with cyclodextrins. AB - The interaction of alpha-, beta- and gamma-cyclodextrins with the anthracycline antibiotics doxorubicin and daunorubicin was investigated by LC, circular dichroism (CD) and absorption spectroscopy. All studies were performed in aqueous media at different temperatures and pH values. The anthracyclines complex only with gamma-cyclodextrin. Lineweaver-Burk and Scott's plots were used to calculate the stability constants of the anthracycline-gamma-cyclodextrin inclusion complexes. PMID- 2100606 TI - Equilibrium kinetics of the new experimental anti-tumour compound SK&F 104864-A in aqueous solution. AB - The equilibrium kinetics of lactone ring hydrolysis in the new experimental anti tumour compound SK&F 104864-A. (S)-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride, have been studied. Only one product is formed, SK&F 105992. A stability-indicating HPLC method has been optimized to perform the analysis. The pH is the main factor influencing equilibrium; at pH greater than or equal to 10 the lactone ring is quantitatively opened while at pH values less than or equal to 4 the lactone form is exclusively present. Other parameters, such as buffer ions and ionic strength, do not influence equilibrium. Complexation with dimethyl beta-cyclodextrin stabilizes the lactone form. Other cyclodextrins do not show this stabilization. PMID- 2100607 TI - Development of a radioimmunoassay for idazoxan hydrochloride. AB - To facilitate the measurement of idazoxan in clinical trials an immunoassay capable of detecting low ng ml-1 concentrations was required. A stable derivative was prepared which, after linking to keyhole limpet hemocyanin (KLH), was subsequently immunized into sheep. Early assay development was carried out with both fluorescent (1-FITC) and iodinated (I-125) labels. The assay methodology was the same in both cases, using magnetizable solid-phase particles to which the antibody was linked. The sensitivity of the assay was such that a large sample volume was required, which in turn, led to problems of increased protein interference. The use of pepsin to digest the protein was used effectively after several blocking agents were unsuccessfully used. The limit of detection was in the region of 3 ng ml-1. Cross-reactivity studies showed that the antibody was specific for idazoxan. Intra- and inter-assay precision was 7 and 12%, respectively. Correlation with the analytical GC-MSD method was in the order of 0.90. PMID- 2100608 TI - Validation of a radioimmunoassay for the determination of human plasma concentrations of lamotrigine. AB - A precise and sensitive radioimmunoassay to determine human plasma lamotrigine (430C78), Lamictal) is described. The method is a direct double antibody procedure employing a rabbit polyclonal first antibody raised to a BSA conjugate of lamotrigine, and an iodinated tyrosine methyl ester of lamotrigine as the tracer. Both reagents are added simultaneously to samples containing lamotrigine prior to an overnight incubation at 4 degrees C. The method has a sensitivity of 20 ng ml-1, when plasma samples are initially diluted 1:20 with phosphate buffer and sample volumes of 20 microliters are used. The intra-assay precision at 40, 80 and 160 ng ml-1 was 6.2, 2.1 and 4.8%, respectively, and the inter-assay precision at 500, 2000, 5000 and 10,000 ng ml-1 was 4.6, 5.7, 4.6 and 5.9%, respectively. The method was specific and showed reasonable correlation with an HPLC method [1]. PMID- 2100609 TI - Comparison of a calixarene-based ion-selective electrode with two automated analyzers for the clinical determination of sodium in blood plasma. AB - Neutral-carrier ion-selective electrodes based on methyl p-t-butylcalix[4]aryl acetate have been prepared that are responsive to sodium ions. The miniaturized catheter-type electrodes were obtained by dip-coating their porcelain tips in a PVC membrane cocktail. Examination of the general performance of the electrodes revealed excellent characteristics in terms of Nernstian response, selectivity, stability, reproducibility and response time. The results from the indirect potentiometric assessment of a large number of plasma samples with the electrodes showed a good correlation with the results from two automated analyzers (Technicon Smac 3, Hitachi 704) and with flame photometric data. Although inconsistencies were observed in the measurement of some plasma samples, the variance seemed to be method-dependent, and the overall performance of the electrodes showed promise as an alternative to the sodium glass electrode. Some factors influencing the standard potential of the measuring cell are discussed as a source of error. PMID- 2100610 TI - A phenobarbital ion-selective electrode without an inner reference solution, and its application to pharmaceutical analysis. PMID- 2100611 TI - Potentiometric investigation of the stability of palladium(II) complex of pralidoxime chloride in aqueous solution. AB - The formation of a complex between palladium(II) chloride and pralidoxime chloride (PAM-2Cl) has been studied by means of potentiometric pH measurements. The real stability constant of the complex in aqeous medium of ionic strength 0.3 M (KCl) at 25.0 degrees C was log Ks = 7.29. This value was close to that (log Ks = 7.02) obtained previously by spectrophotometric methods after appropriate correction with respect to the corresponding value of the acidic constant of PAM 2Cl (pKca = 8.05), which was also determined under the same experimental conditions. PMID- 2100612 TI - Determination of inorganic phosphate in drug formulations and biological fluids using a plant tissue electrode. AB - A suitable biosensor for the analysis of inorganic phosphate was developed by coupling the enzyme glucose oxidase to a slice of potato (Solanum tuberosum) containing the acid phosphatase, and using an amperometric Clark electrode as an indicating sensor. Phosphate concentration can be determined from its inhibition on the acid phosphatase activity. Measurements were carried out at steady-state conditions and the available concentration range of phosphate, repeatability and accuracy, on phosphate standard solutions, were experimentally determined. Finally the sensor was used in pharmaceutical and biological matrices. The results were compared with those ones obtained by Bartlett's spectrometric method. PMID- 2100613 TI - The application of Fourier-transform Raman spectroscopy to the analysis of pharmaceuticals and biomaterials. AB - Near infrared Fourier-transform (FT) Raman spectroscopy is shown to be a useful spectroscopic tool for the molecular structural analysis of drugs and biomedical polymers. The technique has been applied to the non-invasive investigation of the hydrolytic degradation of a biodegradable polymer in water over a period of 15 days and to the analysis of a drug within a polymer vehicle over a wide drug concentration range. This work demonstrates the potential value of FT Raman spectroscopy in the field of pharmaceutical science. PMID- 2100614 TI - 31P-NMR assay of phosphatidylcholine and phosphatidylethanolamine in AL721. AB - A 31P-NMR based method has been developed for the assay of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in AL721. The assay is based on the comparison of NMR signal intensities of the phosphatidyl moiety of PC and PE to the signal of triphenylphosphate (TPP), the internal standard. The assay is specific and reliable for the quantitation of phospholipid mixtures. Its uncertainty, due primarily to low intensity of 31P signals, was estimated at less than 6%. PMID- 2100615 TI - Spectrophotometric investigation of complex formation of an oxime PAM-4Cl with palladium (II) and its analytical application. AB - The colour reaction of 4-hydroxyiminomethyl-1-methylpyridinium chloride (PAM-4Cl) and palladium(II) chloride has been investigated. The optimum reaction conditions, spectral characteristics, conditional stability constant and composition of the yellow water-soluble complex have been established. A new spectrophotometric method is proposed for the microdetermination of PAM-4Cl. PMID- 2100616 TI - Investigation of penbutolol-iron (III) complex and its spectrophotometric determination in tablets. AB - It has been established that penbutolol reacts with iron(III) chloride in the presence of ammonium thiocyanate to form a pink complex (2:1) that is soluble in chloroform with a maximum absorbance at 478 nm. By application of the methods of Sommer and Job involving non-equimolar solutions, the conditional stability constant (log k') of the complex at the optimum pH of 1.5 +/- 0.02 and an ionic strength of (mu) 0.14 M, was found to be 5.769. The molar absorptivity at 478 nm was 136 1 mol-1 cm-1 at pH 1.5 +/- 0.02. The validity of Beer's law has been tested in the concentration range 3-18 x 10(-4) M; the relative standard deviation (n = 8) was 1.52-3.21%. The proposed method was found to be suitable for the accurate, simple and rapid analysis of penbutolol in the bulk drug and in tablets. PMID- 2100618 TI - Development of a microcomputer program for statistical evaluation of potential pharmacokinetic drug interactions. AB - A simple and self-explanatory program in BASIC for the statistical evaluation of potential pharmacokinetic drug interactions is described. This program, using the data (times and drug concentrations) obtained from two different populations, and with the help of graphic computing techniques, allows the determination and statistical comparison of pharmacokinetic parameters (disposition constants, transfer rate constants, area under the concentration-time curves, etc.) for one- and two-compartment open models after intravenous or extravasal administration. The program is organized in subroutines so that it can be easily modified or extended to other pharmacokinetic models by the user. PMID- 2100617 TI - Chemometric investigation of some analytical methods used for the chemical test of foetal lung maturity. AB - The lecithin/sphingomyelin (L/S) ratio is particularly important for the prediction of foetal lung maturity. A package for pattern recognition of analytical chemical data, "Parvus", was used to handle the different values of the L/S ratio obtained experimentally by common amperometric, spectrometric and chromatographic methods for the determination of lecithin. Eight subjects were considered and some interesting conclusions drawn on the equivalence of different analytical methods of determining lecithin in amniotic fluid. PMID- 2100619 TI - A fully automated chromatographic peak detection and treatment software for multi user multi-task computers. AB - A fully automated method is presented for the detection and integration of chromatographic peak software in which the only parameter to define is the data acquisition frequency; this has to be chosen high enough to minimize some Nyquist frequency problems. Programmed in C language, the software is used on a Unix like system (Xenix) to emphasize its automaticity. The performance of the system in liquid chromatography has been studied in respect of noise frequency and intensity. It is shown that the classical signal-to-noise ratio is obsolete for definition of the detection limit since frequency analysis allows some signal filtration; these limitations are described. An example is given of simulation with Gaussian peaks convoluted with noise characterized by its intensity and frequency distribution. The validity of the software is demonstrated for some HPLC separations. PMID- 2100620 TI - A validated HPLC assay for salmon calcitonin analysis. Comparison of HPLC and biological assay. AB - A high-performance liquid chromatographic (HPLC) method is described for the assay of salmon calcitonin. The method uses a 5-microns octadecasilyl silica column (100 x 4.6 mm) at 50 degrees C and an initial mobile phase (flow rate 1 ml min-1) comprising 35% of B (1 M tetramethylammonium hydroxide-water-acetonitrile, 8:392:600) and 65% of A (1 M tetramethylammonium hydroxide-water-acetonitrile, 20:880:100) with linear gradient elution over 21 min to a final mobile phase of 57% B; solutions A and B are adjusted to pH 2.5 with phosphoric acid. Detection was by UV spectrophotometry at 210 nm. The method has been shown to be selective, precise and rapid and, in a collaborative study to give excellent correlation with the results obtained by using the biological assay method of the European Pharmacopoeia. The method, which has been applied successfully to the assay of different batches of salmon calcitonin in bulk drug and in formulated products, is recommended for adoption as the pharmacopoeial assay method. PMID- 2100621 TI - Thermospray mass spectrometer as a quantitative specific, sensitive, detector for liquid chromatography. Its application to the analysis of pyridostigmine in human plasma. AB - A thermospray interface between a HPLC system and a mass spectrometer has been used to develop an assay for pyridostigmine bromide measuring plasma concentrations down to 1 ng ml-1 on a routine basis. Plasma is loaded onto an AASP reversed-phase cartridge, injected onto a HPLC system connected to a Finnigan 4500 mass spectrometer via a thermospray interface and the molecular ion monitored. A deuterated internal standard is used, but calculations with and without the internal standard show its use does not materially improve the quantitation. The precision and accuracy at the limit of quantitation is less than +/- 5% and 95-105%, respectively. The method is used to analyse samples from a bioavailability study by fully automated unattended overnight sample analysis. PMID- 2100622 TI - Liquid chromatographic determination of 2',3'-dideoxyguanosine in human plasma. AB - A rapid assay for 2',3'-dideoxyguanosine (ddG) in human plasma has been developed. The ddG was first extracted from human plasma using solid phase extraction. The extract containing ddG was then assayed with liquid chromatography using an ODS column and a mobile phase of 9% methanol in pH 6.8 phosphate buffer. The overall method had good accuracy (within 2%), linearity (r = 0.9998), sensitivity (LOD = 1.8 ng, S/N = 3) and recovery (greater than 99% for 5-50 micrograms ddG per ml plasma). PMID- 2100623 TI - Assay of caffeine metabolism in vitro by human liver microsomes using radio-high performance liquid chromatography. AB - The low turnover of caffeine in vitro by human liver microsomes makes the study of the metabolic pathways of this compound difficult. Analytical methods with high sensitivity and specificity are needed for the detection of its metabolic products. A method based on the on-line radiometric determination of [8C 3H]caffeine and its principal metabolite (paraxanthine) in man has been developed using reversed-phase high-performance liquid chromatography. The method has been successfully employed in preliminary studies of the kinetics of this reaction. PMID- 2100624 TI - High-performance liquid chromatographic analysis of the new antitumour drug SK&F 104864-A (NSC 609699) in plasma. AB - A high-performance liquid chromatographic (HPLC) assay is described for the determination of the new, investigational antitumour drug SK&F 104864-A and its lactone ring opened form (SK&F 105992). The analytical methodology reported here involves a protein precipitation step with methanol as sample pretreatment procedure. The instability of the drug necessitates that the plasma fraction is obtained within 5 min after blood sampling by centrifugation, immediately followed by protein precipitation with cold methanol (-30 degrees C). The methanolic extract can be stored at -30 degrees C for several days without deterioration of the analyses. Stability data of the drug and its lactone ring opened metabolite in plasma and after methanolic extraction are discussed. The parent drug and the metabolite are separated by reversed-phase ion-pair liquid chromatography on a LiChrosorb RP-18 column, using methanol-water eluent (pH 6.0) with sodium dioctylsulphosuccinate (DOSS) as ion-pairing agent and fluorescence detection. The proposed method has been validated and, subsequently, implemented in a phase I clinical trial for pharmacokinetic evaluation of the new cytotoxic agent. PMID- 2100625 TI - Liquid chromatographic determination of hydralazine in human plasma with 2 hydroxy-1-naphthaldehyde pre-column derivatization. AB - A selective and sensitive high-performance liquid chromatographic method is described for determination of hydralazine and its metabolites in human plasma. The method involves pre-column derivatization with 2-hydroxy-1-naphthaldehyde at pH 1.2. The reaction product and Methyl Red used as internal standard are extracted into dichloromethane and chromatographed in the reversed-phase mode on an ODS-2 column using acetonitrile-aqueous triethylamine phosphate buffer (80:20, v/v) at pH 3 as eluent. The plasma calibration curve of hydralazine is linear in the concentration range 10-500 ng ml-1. The detection limit is 1 ng ml-1 and the relative standard deviation is less than 2.4. In vivo pharmacokinetics of hydralazine in two volunteers after oral administration of 50 mg of the drug is studied using the proposed LC method. PMID- 2100626 TI - High-performance liquid chromatographic determination of amantadine in urine after micelle-mediated pre-column derivatization with 1-fluoro-2,4 dinitrobenzene. AB - Cationic micelles have been used for the derivatization of the anti-Parkinson drug amantadine with the chromophore 1-fluoro-2,4-dinitrobenzene in urine. In the presence of 90 mM cetyltrimethylammonium bromide (CTAB), the conversion of amantadine into its derivative is complete within 4 min at 60 degrees C and pH 11. Such a short reaction time allows a fully automated pre-column derivatization of amantadine in an on-line combination with reversed-phase high-performance liquid chromatography. This cannot be attained when using purely aqueous derivatization mixtures because then the reaction takes some 20 min at the same temperature. Without the use of an internal standard, the repeatability of the automated determination at the 0.5 microgram ml-1 level is ca. 6%, whilst the detection limit is 75 ng ml-1 (S/N = 3). The present study clearly demonstrates that micellar systems can be beneficially used for the on-line precolumn derivatization of amines in urine. PMID- 2100628 TI - Bioselective detection in liquid chromatography by the use of immobilized enzymes. AB - The combination of liquid chromatography and immobilized enzyme reactors (LC/IMER) is a rapidly developing field of research. The enzymes are used to catalyse chemical reactions and thereby facilitate selective detection. In this instance the chemical derivatizations are performed in the post-column mode. The selectivity is demonstrated with respect to interfering compounds present in complex samples. PMID- 2100627 TI - Multidimensional liquid chromatography of opioid peptides: fluorogenic labelling, retention prediction and separation optimization. AB - The ultra-trace analysis of opioid peptides in biological samples can be achieved by multidimensional liquid chromatography with pre-column fluorogenic derivatization with naphthalene-2,3-dicarboxaldehyde in the presence of cyanide ion. However, in order to take full advantage of the high sensitivity possible with detectors based on laser-induced fluorescence or chemiluminescence, each component of the analytical method must be carefully optimized. In this study, strategies are presented for the prediction of retention time and the optimization of separations of derivatized opioid peptides in multidimensional LC systems. PMID- 2100629 TI - Performance evaluation of an aqueous-organic phase separator for post-column reactions in high-performance liquid chromatography, and its application to the enhanced detection of some basic drugs of abuse. AB - A phase separator is described that is suitable for post-column HPLC applications. It operates with commonly used HPLC eluents and immiscible organic solvents as long as the two phases remain immiscible. It is compatible with gradient elution systems. Separation efficiency is routinely better than 0.8, which ensures that analyte peak heights are about 95% of the maximum height under these conditions. An application for the detection of pethidine, cocaine, methadone, piritramide and dipipanone at 0.8-1.8 ng on-column loadings is described. PMID- 2100630 TI - Circular dichroism detection in high-performance liquid chromatography: evaluation of the anisotropy factor. AB - The application of a circular dichroism (c.d.) detection system in HPLC using a chiral stationary phase is presented. The simultaneous measurement of the absorbance and c.d. signal allows the evaluation of the anisotropy factor (g = delta epsilon/epsilon) and thus the determination of the enantiomeric excess (e.e.) of the eluates. When this detection system is used in preparative chiral chromatography the collection of the enantiomeric fractions can be readily optimized. PMID- 2100631 TI - On-line recovery of trimeprazine enantiomers following chiral separation by reversed-phase high-performance liquid chromatography using a beta-cyclodextrin containing mobile phase. AB - A procedure is described which allows the on-line recovery of enantiomers following semi-preparative chiral separation by RP-HPLC using beta-cyclodextrin in the mobile phase. By this method, the phenothiazine antihistamine trimeprazine (I) was resolved into its antipodes at greater than 95% optical purity at a throughput of more than 1 mg of each enantiomer per hour, using 4 mm i.d. columns. The recovered trimeprazine was found to be free from cyclodextrin. PMID- 2100632 TI - Diode array detection of low level co-eluting species in high-performance liquid chromatography. AB - A simple and sensitive method for detecting low levels (0.5 and 1.0%, w/w) of co eluting species in HPLC has been developed. This method is based on the subtraction of normalized peak up-slope and down-slope spectra from that of the apex. Visual inspection of the resultant "difference spectra" allows for a qualitative judgement regarding the integrity of the peak under consideration. PMID- 2100633 TI - Chromatographic and spectroscopic studies on the constituents in male and female flowers of Hagenia abyssinica. AB - The phenolic constituents of male and female flowers of Hagenia abyssinica were examined using chromatographic and spectroscopic techniques. Chromatographic analysis of kosins (phloroglucinols) was carried out using TLC, reversed-phase LC and glass-capillary GLC. Purification of the crude kosins was effected by silica gel column chromatography and purification of phenolic acids using ion-exchange resins and preparative TLC on silica gel. The kosins were characterized by TLC, LC, UV, IR, MS and H1 NMR spectroscopy while the phenolic acids were characterized by UV-spectroscopy, TLC and LC. The phenolic acids found were protocatechuic acid, p-hydroxybenzoic acid and vanillic acid. The content of the kosins and phenolic acids was established quantitatively for both male and female flowers. PMID- 2100634 TI - Reversed-phase high-performance liquid chromatographic method for the assay of 1,4-dioxane in sulphated polyoxyethylene alcohol surfactants. AB - A rapid high-performance liquid chromatographic method has been developed for the assay of 1,4-dioxane in ethoxylated fatty alcohol sulphates. After solid-phase extraction using Bakerbond C18 cartridges, samples were directly analysed on a LiChrospher CH-8 reversed-phase column with UV detection at 200 nm and an acetonitrile-water eluent. Recovery of 1,4-dioxane from the surfactant matrix was 95.7% in the 40 to 120 micrograms g-1 range. The minimum quantifiable amount was 18 micrograms g-1. The procedure is simple, reproducible, specific and suitable for routine analyses of commercial surfactants. PMID- 2100635 TI - Determination of benzalkonium chloride in aqueous ophthalmic preparations by high performance liquid chromatography. AB - A high-performance liquid chromatographic method is described for the determination of homologues of benzalkonium chloride in aqueous ophthalmic preparations. The technique involves direct injection of the sample on a 5 microns Spherisorb-CN column. The mobile phase is acetonitrile-triethylamine (0.1%, v/v) in water (pH 2.5; 40:60, v/v). Detection is carried out at 215 nm. The method is rapid, specific, reproducible and simple, and is especially useful for the assay of this preservative in stability studies and quality control procedures. PMID- 2100636 TI - Chromatographic retention relationships between aliphatic tertiary amines and their putative N-oxide metabolites--preliminary results. AB - The chromatography of a series of tertiary amines and the corresponding N-oxides have been studied and the Functional Group Contribution Approach used to describe retention correlations between them. Good correlations are observed between the behaviour of compounds on HPLC and with the exception of some alicyclic nitrogen compounds also on thin layer chromatography. The models produced are used to predict k' and Rf values for ranitidine N-oxide and tamoxifen N-oxide based upon those for the parent molecule. The deviation between actual and predicted values was larger than expected, presumably due to the structural or physico-chemical differences of ranitidine and tamoxifen compared to the model compounds. PMID- 2100637 TI - Separation of keto-enol tautomers of chlortetracycline and 4-epichlortetracycline by liquid chromatography on poly(styrene-divinylbenzene)copolymer. AB - Keto and enol tautomers of chlortetracycline and 4-epichlortetracycline were successfully separated by low temperature high-performance liquid chromatography on poly(styrene-divinylbenzene)copolymer. The keto-enol tautomerism occurs between C-11a and C-12. The elucidation of the chemical structure of the tautomers was realized with the help of on-line and off-line UV-spectrophotometry and of 13C and 1H NMR spectrometry. The kinetics of the equilibrium reaction were investigated. PMID- 2100638 TI - Assay and purity control of oxytetracycline and doxycycline by thin-layer chromatography--a comparison with liquid chromatography. AB - A thin-layer chromatographic (TLC) method using densitometry is described for the assay and purity control of oxytetracycline and doxycycline. With a mobile phase of dichloromethane-methanol-water (59:35:6, v/v/v) and a silica gel thin-layer, previously sprayed with 10% sodium edetate solution adjusted to pH 9.0, all the potential impurities of oxytetracycline or doxycycline are well separated from the main components and from each other. Results obtained with TLC are compared with those obtained by previously established liquid chromatography (LC) methods using poly(styrene-divinylbenzene) stationary phases. A good correlation was obtained (r greater than 0.9999). For TLC the relative standard deviation (RSD) for the assay of the main component was less than 2%, for LC the RSD was less than 1%. PMID- 2100639 TI - Analysis of biogenic amines and their metabolites in biological tissues and fluids by gas chromatography-negative ion chemical ionization mass spectrometry (GC-NICIMS). AB - GC-NICIMS has been employed in the analysis of biogenic amines and their metabolites in human urine and human, bovine and porcine aqueous and vitreous humour. Several new chemical derivatization procedures have been developed in order to analyse these compounds. Concentrations of octopamines and synephrines were determined in urine from treated and untreated hypertensive subjects and normotensive individuals; there were no significant differences in concentrations of these metabolites between these groups. Human urine contained several dihydroxy-phenylethylamines which have not been reported as natural metabolites before and also 5- and 6-hydroxydopamine in relatively large amounts. Aqueous and vitreous humour contained very low quantities of noradrenaline, tyramine and dopamine but measurements were inconsistent because sometimes the levels were below the limits of detection. Metabolites of a number of biogenic amines were readily detected in aqueous and vitreous humour. PMID- 2100640 TI - Determination of morphine and codeine in urine by gas chromatography-mass spectrometry. AB - GC-MS is one of the recommended analytical techniques for the identification and confirmation of opiates in urine. A method for the qualitative detection and quantitation of codeine and morphine in urine samples by this technique has been developed. This method is also suitable for the detection of their main metabolites in urine: norcodeine and normorphine. It also allows the identification of 6-monoacetylmorphine in urine, which can be used as a confirmatory marker of heroine abuse. The derivatized compounds are separated by capillary gas chromatography (GC) and identified by mass spectrometry (MS) in the selective ion monitoring acquisition mode (SIM). The recoveries from urine at concentrations of 1000 ng ml-1 are 72% for codeine and 80% for morphine. The method is linear in the range studied (0-1000 ng ml-1) for codeine and morphine. PMID- 2100641 TI - Simultaneous detection in urine of cocaine and its main metabolites. AB - The simultaneous detection in urine of cocaine (CO), and the main biotransformation products, benzoylecgonine (BE) and ecgonine methyl ester (EME), is difficult due to their different physicochemical properties. The method presented involves a bonded silica solid-phase extraction procedure that allows mixed ionic and apolar interactions with the analyte. After extraction the compounds are derivatized sequentially with ethyliodide to obtain the BE ethyl ester derivative, and with N-methyl-N-trimethylsilyl trifluoroacetamide (MSTFA) to obtain the O-TMS derivatives. The derivatized compounds are then analysed by a capillary (methylphenylsilicone) gas chromatographic system equipped with a specific nitrogen-phosphorus detector. The method is suitable for the confirmation and quantitation of CO and its main metabolites in urine. BE levels in urine samples (n = 20) measured by the described method and by an immunological technique were in close agreement (r = 0.999). PMID- 2100642 TI - Determination of serum diltiazem concentrations in a pharmacokinetic study using gas chromatography with electron capture detection. AB - An open cross-over randomized clinical trial was performed in nine healthy humans to determine steady-state pharmacokinetics and bioavailability of three oral diltiazem preparations, tablets containing 60 and 90 mg of diltiazem hydrochloride, administered in total daily doses of 180 mg. Serum drug levels were determined by gas chromatography with electron capture detection following a simple extraction procedure. Blood samples were collected before and at several post-dosing intervals after administration of the last dose in steady state, and pharmacokinetic parameters were calculated. The steady-state diltiazem concentrations in sera were determined 48 h after the first dose, and were (mean +/- SD): 46.4 +/- 28.1, 60.8 +/- 36.3 and 36.8 +/- 22.6 micrograms l-1 for Pliva 60, Pliva 90, and Aldizem 90 diltiazem preparations, respectively. The corresponding elimination half-lives were 5.6 +/- 2.0, 5.2 +/- 1.8 and 6.9 +/- 3.2 h; peak concentrations were 88.4 +/- 29.5, 153.5 +/- 86.5 and 139.2 +/- 72.5 micrograms l-1, and areas under the concentration curves (AUC 12 h) were 477.4 +/ 172.5, 989.2 +/- 536.3 and 817.9 +/- 494.5 micrograms h-1, respectively. PMID- 2100643 TI - The identification of polyoxyethylene glycols and related compounds by capillary gas chromatography. AB - A sample work-up method for gas chromatographic profiling of polyoxyethylene glycol (PEG)-related compounds in pharmaceutical matrices is described. After a short sample clean-up, carbon-oxygen linkages are partially cleaved with 0.07 M boron tribromide in dichloromethane at room temperature. The reaction is stopped after 1 min by addition of 0.01 M HCl. The products are trimethylsilylated and injected onto a WCOT 50 m x 0.25 mm CP-SIL 5 CB fused silica column. Eleven model compounds, representing four common types of PEG-derivatives, have been evaluated by this method. The results show that characteristic profiles can be obtained from PEG-derivatives carrying different functional groups. Minimum detectable amounts are in the range of 200 micrograms. PMID- 2100644 TI - Method validation in pharmaceutical analysis. PMID- 2100645 TI - Problems associated with the extraction and analysis of triamcinolone acetonide in dermatological patches. PMID- 2100646 TI - Studies on the metabolism of fluorinated xenobiotics in the rat using 19F-NMR and 1H-NMR spectroscopy. PMID- 2100647 TI - 1H-NMR spectroscopy of biofluids and the investigation of xenobiotic-induced changes in liver biochemistry. PMID- 2100648 TI - Proton NMR studies on the effects of uranyl nitrate on the biochemical composition of rat urine and plasma. PMID- 2100649 TI - Proton NMR analysis of plasma from renal failure patients: evaluation of sample preparation and spectral-editing methods. PMID- 2100650 TI - Proton nuclear magnetic resonance of urine and bile from paracetamol dosed rats. PMID- 2100651 TI - Determination of bromine traces in sodium diclofenac, using X-ray fluorescence spectroscopy. PMID- 2100652 TI - Comparison of FT-IR and AAS for metalloimmunoassay of a tricyclic antidepressant drug (desipramine). PMID- 2100654 TI - Dissolution testing using continuous multicomponent UV analysis to correct for excipient interference. PMID- 2100653 TI - Spectrophotometric determination of furosemide and its palladium(II) complex. PMID- 2100655 TI - Enzymatic flow injection method for determination of formate. PMID- 2100656 TI - The determination of small quantities of water in single vials of pharmaceutical products by flow injection analysis. PMID- 2100657 TI - Anodic oxidation of some phenothiazine derivatives on pretreated platinum and ruthenium electrodes. PMID- 2100658 TI - A clinical evaluation of dentinal slot, amalgapin & T.M.S. retention in amalgam restorations. AB - In this study, clinical performance of Dentinal slot, Amalgapin & Pin Retained Amalgam restoration was evaluated. The study was performed in 20 patients requiring extensive restoration. Clinical evaluation was done by two caliberated experts at 6 months, one year, & one & half year duration. It was concluded that Dentinal slot restorations showed better clinical performance than the Pin retained restorations. However results of Amalgapin restorations were not that promising. PMID- 2100659 TI - Clinical management of dentin hypersensitivity using cathode and anode iontophoresis. AB - A clinical study was undertaken to study the desensitising effect of Anode and Cathode iontophoresis using solutions and gels. A total number of sixty patients were selected, divided into four groups and subjected to the following methods of treatment. a) Anode Iontophoresis using strontium Chloride Solution (9%) b) Anode Iontophoresis using Strontium Chloride gel (9%) c) Cathode Iontophoresis using Sodium Fluoride solution (2%) d) Cathode Iontophoresis using Sodium Fluoride gel (2%) Distilled water was used as the control Sensitivity was evaluated objectively with the help of specially designed apparatus which delivered measurable electrical stimuli. The results showed a statistically significant difference in the reduction of tooth sensitivity using Strontium Chloride (9%) both as a gel and solution as compared to Sodium Fluoride (2%) gel and solution. PMID- 2100660 TI - Bifid root and root canal in mandibular second premolar and its management--a case report. AB - Morphogically the mandibular second premolars present one root canal (97.5%). So far only a small percentage (2.5%) of cases were reported to have two root canals where they present the canals on the buccal and lingual direction of the root. Here an unusual case of two root canals, which are situated in mesial and distal direction is presented. PMID- 2100661 TI - Bonding--a clinical review. PMID- 2100662 TI - Fracture resistance of dowel channel preparations with various dentin thickness. AB - This in vitro study consisted of 40 cast dowel core made of technique metal alloy. They were divided into 4 groups of dowel channels with 1 mm facial dentin thickness, 2 mm facial dentin thickness, 1 mm facial dentin thickness with 60 degrees bevel for the metal collar and 2 mm facial dentin thickness with 60 degrees bevel in the metal collar, respectively. The fracture resistance under horizontal force were compared by using Instron machine. From the study, it was found that more than 1 mm thickness of labial dentin wall of post channel is required to prevent root fracture under horizontally directed force and an addition of 2 mm collar in the core around the root enhanced the resistance to root fracture. It was also found that adequate post diameter should be present when technique metal was used to prevent dowel failure due to bending under force. PMID- 2100663 TI - Betel chewing and dental decay. AB - A survey was carried out on Four hundred and sixty patients to find out the effects of betel chewing on dental caries & oral hygiene. It was found that among the betel chewers as well as the non betels chewers., the highest caries susceptibility was in the age group of 20-34 years. Also caries susceptibility was higher among the females as compared to males. It was also observed that though the habit of betel chewing reduces the incidence of dental decay, maintenance of oral hygiene is very poor. PMID- 2100664 TI - Brittle gutta percha cones can be rejuvenated. PMID- 2100666 TI - Laser in caries detection. PMID- 2100665 TI - Comparative evaluation of marginal leakage of different types of silver amalgam alloys in vitro--a microfluoroscopic study. AB - A study was carried out in vitro to evaluate the amount of microleakage using seven different Silver amalgam alloy using Fluorescein dye. Among the high copper alloy used in this study, the admixed alloy showed least marginal leakage followed by the high copper lathecut alloy and the high copper spherical alloy. It was also observed that the marginal penetration of the conventional alloy are much more than the high copper alloy. PMID- 2100667 TI - The effect of metronidazole on the anaerobic microorganisms of the root canal--a clinical study. AB - The antibacterial effect of 0.25% metronidazole solution as root canal irrigant on anaerobic bacteria was studied in ten central incisors. Each tooth was treated at four appointments, and the presence of anaerobes in the root canal was studied on each occasion. No antibacterial intracanal dressings were used between the appointments. No anaerobes could be recovered from any tooth on the fifth appointment. In the control group, where normal saline was used as an irrigant, anaerobes could be recovered in four of the ten canals. These results suggest that 0.25% metronidazole solution is more effective than saline solution as a root canal irrigant. PMID- 2100668 TI - Etching and bonding on enamel. PMID- 2100669 TI - Attainment of hermetic seal with decalcified allogenic bone matrix grafts- surgical vs. conservative approach. AB - Twenty four non vital upper anterior teeth from twelve healthy patients, between the ages of 18-30 years, having definite radiolucent areas at the periapex, were taken for this study. A comparison was made between the surgical and conservative approach, using decalcified allogenic bone matrix (DABM) grafts to achieve a physiologic seal at the root apex. The period of observation were 60 days, 120 days and 180 days. The clinical and radiological finding of this study strongly support the observation that DABM accelerates osteogenesis and cementogenesis which seal the root apex through a physiological process. The process of healing was quicker when the surgical approach was used. However a longer period of observation and histological study is required before any conclusion can be drawn, as regard the choice of a surgical or conservative approach. PMID- 2100671 TI - [Employment of a dental hygienist in Germany. 1. Experience and reminiscence of three decades]. AB - Dental hygienists in most European countries and in America are highly qualified assistants to the dentist's daily professional life. Especially for long lasting achievements in periodontal therapy and maintenance, the hygienist's help is absolutely essential. All attempts to introduce a similar vocational reputation, as well as an adequate career training course throughout the Federal Republic have failed so far. PMID- 2100670 TI - [Immunological aspects of periodontal diseases. Prospects for diagnosis and therapy]. AB - Achievements in bacteriology and immunology have significantly contributed to the understanding about the etiology and pathogenesis of periodontal diseases. Studies have demonstrated that interactions between bacteria and the immune system play a central role in the etiology of periodontal disease. In the immune system four components can be distinguished according to their function in the periodontium. These include a) the secretory system; b) the polymorphonuclear leukocytes, antibody and complement system; c) lymphocytes and monocytes; d) the immunoregulatory system. Polymorphonuclear leukocytes are of utmost importance for the maintenance of periodontal health. In neutrophil defects severe periodontal diseases are frequently found. Prepubertal periodontitis, juvenile periodontitis and rapidly progressing periodontitis are examples for the periodontal manifestation of neutrophil defects. Therapy of periodontal disease that is related to immune defects requires a modified treatment plan. Efforts are being made to extend the diagnosis, prevention and therapy of periodontal diseases. Presently, biochemical, immunological and microbiological methods are being evaluated for their clinical applicability. Preliminary results indicate that, in the future, biochemical markers in the gingival crevicular fluid may be used for the diagnosis of active sites. Therapy may be enhanced by the administration of non-steroidal anti-inflammatory drugs and specific antimicrobials. However, before these methods can be applied in clinical periodontics, further long-term studies are needed. PMID- 2100672 TI - [Instrumentation for periodontal treatment]. AB - Since the introduction of scalers in the beginning of the century for the mechanical removal of plaque, instruments with few major modifications are still in clinical use today. New approaches in diagnosis of periodontal disease such as microbiological analysis, enzyme diagnosis of crevicular fluid or computer-aided procedures are presently in clinical trials. A set of periodontal instruments is presented which has been well established and is recommended for the treatment of periodontal disease. The discussion of the specific instruments is presented according to the sequence of patient treatment, which is divided into diagnosis, initial therapy, scaling and root planing, periodontal surgery and maintenance therapy. PMID- 2100673 TI - [Osseointegrated fixtures ad modum Branemark--indications in the dental office]. AB - Through the use of osseointegrated fixtures ad modum Branemark we have the possibility to solve prosthetic problems. Three cases are described. They demonstrate that the use of osseointegrated fixtures combined with the concept of a reduced occlusal table can provide good functional stability. PMID- 2100674 TI - [Rehabilitation of an edentulous patient with implant supported all-porcelain bridges after orthognathic surgery]. AB - This case report presents a 43-year-old woman who was not happy with her complete dentures both from the functional and the esthetic point of view. The combined therapy of orthognathic surgery, insertion of endosteal oral implants and the loading with all-porcelain cantilevered bridges made out of In-Ceram is reported. PMID- 2100675 TI - [New Gracey- and furcation curettes. A significant advance in standard instrumentariums]. PMID- 2100676 TI - [Glossary of basic definitions for dental practice]. PMID- 2100677 TI - [Direct bone anchorage of oral implants: clinical and experimental considerations of the concept of osseointegration]. AB - The term osseointegration is analyzed in relation to its theoretical and clinical definitions, and comparisons are made to other implant modalities. The term osseointegration has a clear clinical meaning, but there is doubt about its precise usage in an experimental setting. Clinically, an implant can be described as osseointegrated if there is no discernable movement when force is applied to the fixture. This is in contrast to implants surrounded by fibrous connective tissue, which move within soft tissue. Newly developed laboratory techniques may be used in the future to precisely characterize osseointegration in the laboratory. PMID- 2100678 TI - [Employment of a dental hygienist in Germany. 2. The cooperation between dentist and dental hygienist in day to day practice]. AB - The comprehensive range of functions in a dental practice with special emphasis on periodontal cure requires cooperation amongst highly qualified personnel. The dental hygienist has a special standing and is responsible for as well as in charge of important treatment stages, as much as the dentist himself. The treatment stages are of greater relevance to long-lasting therapeutic achievements. PMID- 2100679 TI - [Treatment-effect on cyclosporin A-induced gingival hyperplasia in patients with organ transplantation: a longitudinal study]. AB - In the present study a newly developed concept for avoiding recurrences after the periodontal surgical treatment of cyclosporin A-induced gingival hyperplasia is described. Conventional gingivectomy results in restitutio per secundam, which promotes recurrences. To avoid this we tried to achieve a restitutio per primam by using a modified surgical technique. Ten patients, four treated under general anesthesia and six on an outpatient basis, were treated with this technique. Patients were monitored for 20 month. Pre- and postoperative care was performed in a standardized manner for all patients. During the surveillance, a long-term suppression of the cyclosporin-induced gingival hyperplasia could be found, but it was not possible to avoid recurrences totally. PMID- 2100680 TI - [The implant/tissue interface in a clinical perspective]. AB - For a proper insight in the implant/tissue interface of permucosal oral implants it is good to refer to the tooth/periodontium interface. Although there are evident differences such as the lack of a periodontal ligament with its possibilities for eruption and migration and elaborate neural endings, it seems that classical periodontal parameters are the yardstick to discriminate failure from success of oral implants. Long cone radiographs and mobility assessment seem the only available clinical tools to detect a scar tissue interposition. On the other hand, their discrimination power is insufficient to prove close bone apposition. Further studies are needed to interpret the observations that around failing implants the subgingival microflora resembles that of active adult periodontitis. Periodontologists can learn a lot from the implant/periodontium interface to get a better understanding of the tooth/periodontium complex. PMID- 2100681 TI - [The episodic progression of untreated adult periodontitis]. AB - Marginal periodontitis in humans and animals is characterized by site-specific episodes of accelerated clinical attachment loss, which are interspersed between periods of quiescence of variable length. Diagnosis of episodic periodontitis progression could allow for early interception and arrest of progression. Currently available diagnostic techniques are not sensitive enough to detect phases of periodontitis progression. Diagnostic tests should be developed which are sensitive and practical enough to determine need and success of periodontal treatment at specific sites or sections of a dentition. In a longitudinal study on untreated periodontitis in humans, progressing and nonprogressing periodontal lesions were identified and investigated using clinical, microbiological, histological and immunohistochemical methods. Ten adult patients with untreated advanced periodontitis were monitored monthly for ten months. Attachment levels and probing depth were determined at six sites of every tooth. Corresponding contralateral sites were identified where one site had lost 2 mm or more probing attachment since the previous session (P-site), and the other site had not (C site). The results showed that bleeding on probing was positively and statistically significantly correlated with episodic clinical attachment loss. The error in probing attachment level measurements varied with the tooth type and was greatest at molars. Over time the measurement error became smaller. In deeper pockets the probing error was greater than in shallow pockets. It appears that in order to accept clinical progression of periodontitis an increase in probing attachment loss or probing depth of more than 2 mm has to be observed. Using the mean attachment loss per site in a dentition at six or nine months after initial measurements should enable the dentist to discriminate patients with a higher rate of periodontitis progression from patients with a low rate. Darkfield microscopy used for assessment of subgingival bacterial populations seems to be without diagnostic value for differentiation between P- and C-sites. PMID- 2100682 TI - [Collagen as a basic element of the periodontium: immunohistochemical aspects in the human and animal. 1. Gingiva and alveolar bone]. AB - The connective tissue (CT) is responsible for stability and function of the whole periodontium. It consists of cells, which are embedded in the extracellular matrix. Collagen plays the main role for the function of the periodontal unit. Collagen types I, III, IV, V and VI are distributed in a different pattern in all periodontal tissues, as has been here demonstrated in the gingiva and alveolar bone. Collagen type I, as a characteristic collagen type of the hard tissues, has been demonstrated by thick collagen fibers in the alveolar bone and in the gingival connective tissue. It can be differentiated from the thinner collagen type III fibers, which are localized in the gingiva (especially under the basement membrane of the epithelium) as well as only in the bone marrow stroma. The epithelium, blood vessels and nerves contain the characteristic collagen type IV in their basement membrane Filamentous (collagen type V) and microfibrillar (collagen type VI) components demonstrate different patterns of distribution, especially around the bone cells and in contrast to the other collagen types of fibrillar networks in the gingival CT. This morphological differentiation of the extracellular matrix components of the periodontium allows conclusions in the pathological and inflammatory processes as well as in the regenerative and reparative procedures. PMID- 2100683 TI - [Rational removal of fixed restorations]. PMID- 2100684 TI - [Glossary of basic definitions for dental practice]. PMID- 2100685 TI - Secondary hyperlipidaemia. AB - Secondary hyperlipidaemia is common and occurs frequently in disorders such as obesity, alcoholism, diabetes mellitus, hypothyroidism, liver and renal diseases and as a side-effect of drug therapy, particularly for hypertension. Its management may be important to prevent complications such as coronary heart disease and acute pancreatitis. Its study provides many fascinating insights into lipoprotein pathophysiology. PMID- 2100687 TI - Policies for the prevention of coronary heart disease through cholesterol lowering. AB - Policies for coronary heart disease prevention through cholesterol-lowering have been advocated by groups in the UK, the US and Continental Europe. Such policies are based on studies of the atherosclerotic plaque, experimental animals, genetic disorders, and lipoprotein metabolism, and from different epidemiological studies and clinical trials. Surveys of physicians and the public indicate a growing awareness of the importance of cholesterol. Expert groups advocate mutually compatible high-risk and population-based strategies. Selective or whole adult population screening is being discussed as is whether it should be done exclusively in the doctor's office or should also include mass public screening. Improved standards for public screening are necessary. The US National Cholesterol Education Program has developed or is developing reports on: (1) the detection, evaluation and treatment of high blood cholesterol in (a) adults and (b) children and adolescents; and on (2) standardization of cholesterol measurement and (3) population-based strategies for controlling cholesterol. PMID- 2100686 TI - Treatment of hyperlipidaemia. AB - The primary goal of therapy in the treatment of hyperlipidaemia is to reduce the plasma concentrations of known atherogenic lipoproteins thereby reducing or even reversing the flux of lipids from plasma into the arterial wall. A less common goal is to prevent the adverse sequellae of hyperchylomicronaemia in patients with severe hypertriglyceridaemia. The aetiologic factor(s) responsible for hyperlipidaemia in a given patient need to be clearly established and it is important not to overlook potentially treatable secondary disorders. Diet is the cornerstone of therapy in the treatment of hyperlipidaemia; the decision to begin drug therapy should be individualized and should be made only after an adequate trial of diet has failed to achieve satisfactory concentrations of plasma lipids and lipoproteins. In this review I will discuss the use of diet and drugs in the treatment of patients with hypercholesterolaemia due to increased plasma concentrations of low density lipoproteins, patients with combined hyperlipidaemia in which very low and low density lipoproteins are elevated and patients with severe hypertriglyceridaemia in which chylomicronaemia is present. PMID- 2100689 TI - Lipids and cardiovascular disease. PMID- 2100688 TI - Cholesterol as a risk factor for coronary heart disease. AB - The intense current interest in lipids as causal risk factors in coronary heart disease has encouraged a unifactorial, one-dimensional approach to coronary risk based on fixed total serum cholesterol or low density lipoprotein (LDL) cholesterol cut-points. Epidemiological evidence shows that coronary heart disease risk is multifactorial; the risk associated with a given lipid value is modulated overwhelmingly by the level or presence of other factors. While populations with high lipid values may be characterized as being at high risk, individual risk cannot be determined by isolated lipid measurements. To characterize individuals as at high or low risk by considering lipid values alone results in serious misclassification. Cut-points derived from middle-aged American men create anomalies when applied to different age and sex groups and to different populations. Clinical management of risk factors in individuals should involve the negotiation of a flexible and multi-dimensional individual regime, comprising all modifiable factors. PMID- 2100690 TI - Introduction: lipids and coronary disease--resolved and unresolved problems. AB - To my mind, there are more unresolved problems regarding lipids and cardiovascular diseases than those which have been settled. While this may seem disappointing after 40 years of intensive research, the progress which has been made is remarkable and impressive. It is appropriate, therefore, to begin an introduction by outlining the issues which have been resolved and which are more or less internationally agreed. In doing so, I shall deliberately not digress into causes of coronary heart disease (CHD) other than lipids, even though other influences may be as or more important in relation to its pathogenesis. PMID- 2100691 TI - Structure and regulation of the LDL-receptor and its gene. AB - The structural features necessary for the efficient functioning of the LDL receptor are beginning to emerge from investigation of naturally-occurring and artificially-produced mutations in the gene. Six of the seven repeated sequences in the highly-structured NH2-terminal region are needed for optimal binding of LDL and some of the detailed requirements have been elucidated. The membrane spanning region is required for insertion of the protein into the plasma membrane, and the cytoplasmic region for internalisation and self-association. Many apparently unrelated mutations affect receptor processing in the Golgi and the role of the carbohydrate chains remains obscure. The main means of regulating LDL-receptor activity is through repression of gene transcription by sterols. This requires a specific element in the promoter region and probably involves more than one transcription factor. Independent effects could be achieved by modulating the activity of these factors. PMID- 2100692 TI - DNA based diagnostic tests: recombinant DNA and cardiovascular disease risk factors. AB - Advances in molecular biology and medical biotechnology are continuously creating exciting possibilities for DNA based diagnostics. It is now possible by simple procedures to detect polymorphic DNA markers, structural variants and regulatory mutants of human genes, allowing detailed genotyping of patients. The innovative combination of immunoenzymatic techniques, monoclonal antibodies and recombinant tracer proteins, results in new DNA based tests for the determination of important biochemical parameters, in order to define more precisely the phenotype and hence assess the individual risk. The application of these technologies to the analysis of dyslipidemias, atherosclerosis and cardiovascular diseases may not only lead to a better understanding of the molecular and genetic basis of these pathologies, but also to their early recognition and better management. PMID- 2100693 TI - Pathology of atherosclerosis. AB - This communication gives a brief account of the morphology and natural history of atherosclerosis. It defines atherosclerosis, in dynamic terms as the resultant of three interacting sets of processes: accumulation and modification of plasma derived lipid within the arterial intima, connective tissue proliferation and connective tissue necrosis forming an atheromatous pool at the plaque base. The first of these leads to the accumulation of lipid-filled macrophages within the affected intima and this step is most probably mediated via oxidative modifications of the low density lipoprotein molecule. An alteration of the functional phenotype of the intimal smooth muscle cell as a result of interactions with growth factors (most notably PDGF) constitutes the basis for the connective tissue proliferation. Plaque necrosis, which is extremely important as a risk factor for acute thrombosis, is the least well understood area; the activated macrophage may well play a significant role in this connexion. PMID- 2100694 TI - Primary hyperlipidaemia. AB - It is estimated that over 60% of the variability in serum lipids is genetically determined, most of this variation being due to polygenic influences. Interaction between the latter and environmental factors is probably the commonest cause of hyperlipidaemia in the general population. Familial forms of hyperlipidaemia are usually more clearly defined, especially those which have a monogenic or dominant pattern of inheritance, but are less common. This type of disorder, exemplified by familial hypercholesterolaemia, is expressed independently of environmental influences. In contrast, in familial type III hyperlipoproteinaemia inheritance of the underlying gene defect is often insufficient to produce hyperlipidaemia unless additional environmental or genetic influences coexist. Rarely, hyperlipidaemia is recessively inherited, as in familial deficiency of lipoprotein lipase and of apolipoprotein CII. Primary hyperlipidaemias characterized by severe hypertriglyceridaemia predispose to acute pancreatitis whereas those disorders characterized by hypercholesterolaemia, apart from hyper alpha lipoproteinaemia, are associated with an increased risk of premature vascular disease. PMID- 2100695 TI - [Cool lasers in dental medicine]. PMID- 2100696 TI - Two-dimensional gel electrophoresis of urinary proteins in kidney diseases. PMID- 2100697 TI - Altered loop segment function is the initial event in precipitation of low molecular-weight proteins in the rat nephron. PMID- 2100698 TI - Serum peptides and protease activity following renal transplantation. PMID- 2100699 TI - Evolution of serum proteins and amino acids on hemodialysis and after kidney transplantation. PMID- 2100700 TI - Urinary excretion of complement C3 and its decay products in children with kidney transplants. PMID- 2100701 TI - Correlation between protein to creatinine ratio in a single urine sample and daily protein excretion. PMID- 2100702 TI - Significance of Tamm-Horsfall protein excretion in diabetes mellitus and cisplatin nephrotoxicity. PMID- 2100703 TI - Urinary albumin charge and tubular alterations in diabetic microalbuminuria. PMID- 2100704 TI - Exercise-induced proteinuria in diseases with metabolic disorders. PMID- 2100705 TI - Glomerular barrier function for serum proteins in experimental heart failure. PMID- 2100706 TI - Urinary albumin excretion in smokers and non-smokers. PMID- 2100707 TI - Effects of nitrendipine and captopril on nephritic rats. PMID- 2100708 TI - Dietary proteins affect proteinuria in primary membranous glomerulonephritis with nephrotic syndrome and normal renal function. PMID- 2100709 TI - Renal response to acute protein loads: hyperfiltration and proteinuria are time related effects not influenced by the quality of ingested proteins. PMID- 2100710 TI - Influence of exogenous protease inhibitor (Bowmann-Birk inhibitor) in gentamicin induced nephrotoxicity in rats. PMID- 2100711 TI - Latex-enhanced immunoturbidimetric assays of specific proteins in the monitoring of renal function. PMID- 2100712 TI - Mechanisms of nephrotoxicity of beta-lactam antibiotics. PMID- 2100713 TI - Cisplatin nephrotoxicity and platinum-metallothioneins: uptake and toxicity in proximal tubular cells from rat kidney. PMID- 2100714 TI - Acute ciclosporin nephrotoxicity in renal transplant patients. PMID- 2100715 TI - Renal effects of a radiocontrast agent in aging spontaneously hypertensive rats. PMID- 2100716 TI - Tubular histuria: clinical evaluation of the different nephrotoxic potential of X ray contrast media. PMID- 2100717 TI - The pathogenesis of polycystic kidney disease. PMID- 2100718 TI - Glomerular basement membrane-related peptides of human urine induce antihuman glomerular basement membrane antibodies and autoimmune kidney lesions in mice. PMID- 2100719 TI - Antidiuretic hormone secretion related to pressure into the inner ear. PMID- 2100720 TI - T lymphocyte subpopulations, plasma cortisol and ciclosporin in kidney transplanted subjects: a chronobiologic approach to the adrenal-immune system. PMID- 2100721 TI - Measurement of the glomerular sieving coefficient of endogenous proteins in man. PMID- 2100722 TI - Alternate pathways for the renal processing of insulin. PMID- 2100723 TI - Studies on insulin receptors of brush-border membranes isolated from human kidney proximal tubule. PMID- 2100724 TI - The distribution of calcitonin in rat kidney: an immunocytochemical study. PMID- 2100725 TI - Inhibition of the renal tubular reabsorption of rat beta-2-microglobulin by lysozyme in perfused rat. PMID- 2100726 TI - Analysis of urinary albumin charge by direct immunofixation in ultrathin polyacrylamide matrices. PMID- 2100727 TI - Tubular reabsorption of pepsinogen A isozymogens in man. PMID- 2100728 TI - [A study on transovarial transmission of dengue type 1 virus in Aedes aegypti]. AB - The main purpose of this study is to determine the possibility of transovarial transmission of dengue type 1 virus, which was isolated from the serum of a patient with dengue fever during the 1987 dengue epidemic in southern Taiwan, in Aedes aegypti of Kaohsiung strain (KH). Parent female mosquitoes were inoculated with dengue 1 virus by intrathoracic inoculation technique. The F1 offspring adults collected from three sequential ovarian cycles were pooled to become 51, 13 and 14 pools, respectively. All pools were individually inoculated into C6/36 cells and then were detected by direct immunofluorescence antibody technique. Ten, five and three pools, respectively, among these three ovarian cycles turned out to be positive. It revealed that the minimum infection rates (MIR), were 1:254.6 (2,546 mosquitoes), 1:133.6 (668 mosquitoes) and 1:238 (714 mosquitoes), respectively. Meanwhile, the estimated filial infection rates were calculated to be 0.44%, 0.97% and 0.48%, respectively. Since viral antigen has been detected in the tissue of maturing eggs within ovarioles, the results exhibited the possibility that dengue type 1 virus can be transovarially transmitted to the next generation. PMID- 2100729 TI - Effect of exogenous fat emulsion on phagocytic activity of polymorphonuclear cells in septic rats. AB - The effect of exogenous fat emulsion on phagocytic activity of polymorphonuclear (PMN) cells in sepsis was studied in rats. The rats were divided into four groups. Group I, non-septic rats received saline infusion; group II, non-septic rats received exogenous fat emulsion; group III, septic rats received saline infusion; and group IV, septic rats received exogenous fat emulsion. Twenty hours after operation to induce sepsis, normal saline or exogenous fat emulsion was injected. Two hours later, the animal was sacrificed and the blood harvested. PMN cells were isolated from the blood, and phagocytic activity of the cells was studied by culture with Candida albicans. The results revealed that although sepsis led to a suppression of phagocytic function of PMN cells, infusion of exogenous fat emulsion had no deterious effect on the cell phagocytic activity in either septic or non-septic rats. PMID- 2100730 TI - Continuous methacholine inhalation provocation with resistance monitoring in asthmatic patients. AB - Continuous methacholine inhalation with simultaneous bronchial resistance monitoring was performed in 15 controls and 26 asthmatic patients. The subjects were in quiet tidal breathing, and the airway resistance measured by forced oscillation method were continuously recorded with X-Y recorder. The mean airway resistance of the asthmatic patients was higher than that of the control group, so was the conductance of the asthmatics lower than that of the control. All the asthmatics were responsive to the methacholine test, while only two controls had the response. No correlation could be obtained between bronchial reactivity and sensitivity, but the bronchial sensitivity was correlated with serum total IgE (r = 0.448; p less than 0.05), and suggest that the higher the IgE is, the more sensitive the asthmatic patients respond to methacholine. Continuous methacholine provocation is useful in the diagnosis of bronchial asthma and is more safe and time-saving compared with conventional intermittent method. PMID- 2100731 TI - Dynamic modelling of the growth of a surface fungal colony. AB - The growth of a surface fungal colony in the three-dimensional space was modeled kinetically. The present analysis led to the conclusion that the radius of a fungal colony increases exponentially in the initial period followed by a constant increase in its radius at large times. This is justified by analyzing the available experimental data. The elevation of a fungal colony was limited by a balance of the transport of protoplasm inside a growing hyphae and a maintenance factor. A numerical simulation revealed that a typical fungal colony had a disk-shaped base with a flat top and a side face generated by rotating a concave upward curve about a vertical axis. PMID- 2100732 TI - Clinical experience with halofantrine in the treatment of malaria. AB - Halofantrine hydrochloride (HF) belongs to a new class of antimalarials, the phenanthrene methanols. Preliminary clinical studies suggested that an adult dose of 500 mg 6-hourly for three doses, with a weight-based regimen of 8 mg/kg 6 hourly for three doses in children, would be effective. In an ongoing clinical programme, 1973 patients with acute malaria were analysed, of whom 1474 (1315 with P. falciparum and 122 with P. vivax malaria) received the above regimen. In the studies 931 adults and older children were treated (61 with capsules and 870 with tablets) while 520 infants and young children used 5% or 2% suspension. The majority of studies were performed in areas of high chloroquine or multidrug resistance. Only eight (0.6%) of 1282 evaluable patients with falciparum malaria failed to clear their parasitaemias within 7 days. Recrudescence of parasitaemia occurred in 77 patients (6.0%). Reinfection cannot be excluded in several of the cases, where protection from malaria transmission was not maintained. The majority of recrudescent patients were either non-immune (normally residing in malaria-free areas) or were infants below 2 years of age. In vivax malaria cases, there were six recrudescences (5.4%). The mean parasite clearance time was 57.9 h and the fever clearance time 50.2 h in falciparum malaria cases, while the clearance times for vivax cases were 57.3 h and 49.6 h respectively. Clinical events were uncommon and consisted of mild transient diarrhoea or abdominal pain in less than 5% of cases. Laboratory findings were generally abnormalities related to the acute disease rather than drug treatment. Experience to date would indicate that HF is a safe and useful drug for the treatment of acute malaria, particularly in areas where there is extensive resistance to current antimalarials. PMID- 2100733 TI - Susceptibility of several species of Candida and Torulopsis to fluconazole and ketoconazole. AB - The authors compared the in vitro antifungal activity of fluconazole, a new triazole antifungal agent, and ketoconazole, an imidazole derivative. The MIC values were determined against 50 strains of Candida albicans, 10 strains of C. guilliermondii, 10 strains of C. krusei, 10 strains of C. parapsilosis, 10 strains of C. pseudotropicalis, 10 strains of C. tropicalis and 15 strains of Torulopsis glabrata. The fungistatic activity was evaluated by the agar dilution method using BHI and casitone media after incubation for 48 h at 28-30 degrees C. Both antifungal agents showed higher activity when tested on casitone medium; however, the G-MIC values for ketoconazole were lower than those for fluconazole. PMID- 2100734 TI - In vitro activity of oral cephalosporin BAY v 3522 compared with other oral cephalosporins. AB - Minimal inhibitory concentrations (MICs) of the oral cephalosporin BAY v 3522, and of cephprozyl, cefaclor, cefixime, cefuroxime, cefetamet, cefpodoxime and cefotaxime were determined against Gram-positive and Gram-negative clinical isolates with the NCCLS agar dilution procedures. BAY was the most active drug against Gram-positive organisms. MICs ranged from 0.01 mg/l against group A streptococci to 16 mg/l against S. faecium. Although mean MICs of BAY against methicillin-resistant S. aureus and S. epidermidis were between 0.9-1.8 mg/l, respectively, such strains showed typical heteroresistance in population studies. In addition, the biochemical correlate of methicillin-resistance, the PBP-2', showed similar low affinity to BAY as methicillin. beta-lactamase-producing H. influenzae and B. catarrhalis were inhibited by 2-8 and 0.25-2 mg/l, respectively, whereas non-producers were inhibited by 0.25-2 and 0.12-1 mg/l of the drug. The activity of BAY against enterobacteriaceae was rather low. Ampicillin-susceptible E. coli strains were inhibited by 2-8 and resistant strains by 8-32 mg/l. The mean MIC against cephalothin-susceptible K. pneumoniae strains was 2.8, and that against resistant strains 27.4 mg/l. MICs against beta lactamase-producing enterobacteriaceae determined in broth dilution were 4-8 times higher than those determined in agar dilution. Bactericidal activity was measured in killing-curve experiments at 4 times the MIC. BAY killed equally well as standard control drugs. PMID- 2100735 TI - Protective action of propionyl-L-carnitine on toxicity induced by hyperbaric oxygen. AB - The protective effect of propionyl-L-carnitine against hyperbaric oxygen toxicity was studied by in vivo experiments on mice. The treatment reduced both the percentage of animals with convulsions and the death rate. Tissue signs of toxicity and pulmonary weight increase were less marked in treated animals than in controls. Results may indicate that propionyl-L-carnitine needs to build up to critical levels in cells and mitochondria before its metabolic effects can be fully felt. PMID- 2100736 TI - Toxicity of disodium sebacate. AB - Investigations of the acute toxicity of disodium sebacate after oral, i.p. and i.v. administration were carried out on 220 Wistar rats (110 males and 110 females) and 204 New Zealand rabbits (102 males and 102 females). No oral acute toxicity was found. On the contrary LD50 +/- s.e. of 5500 +/- 830 mg/kg b.w. and 6000 +/- 850 mg/kg b.w. were found respectively for rats and rabbits after i.p. sebacate administration. When sebacate was given i.v., the median lethal dose +/- s.e. was 560 +/- 86.5 mg/kg b.w. for rats and 1400 +/- 267.2 mg/kg b.w. for rabbits. Similar results were obtained in corresponding groups of animals (in total 220 rats and 204 rabbits) given oral, i.p. and i.v. saline solutions with added glucose in order to obtain the same value of osmolarity and sodium ion concentration. The above results appear indicative of low toxicity of disodium sebacate, and suggest that the toxic effects found could be due to the sodium content of the compound administered. Similarly, subacute and chronic toxicity was investigated in forty rats and forty rabbits (twenty males and twenty females) fed disodium sebacate incorporated into pellets. When compared to the control animals, no significant differences in biological parameters (clinical, chemical and haematological values, growth curves and histological findings for the different organs) were observed in the test groups during the treatment period. In addition, fetal toxicity, teratogenicity and neonatal toxicity were investigated in twenty female rats and twenty female rabbits. Sebacic acid did not show any teratogenic effect and the development of the fetuses was regular. PMID- 2100737 TI - Immunomodulatory effects of two extracts of Panax ginseng C.A. Meyer. AB - The effect of Panax ginseng extracts on cell-mediated immune functions in man has been investigated. Three groups, each consisting of twenty healthy volunteers, were treated under conditions of double blindness with capsules containing lactose (Control Group B), with capsules containing 100 mg of aqueous extract of the drug (Group A), and with capsules containing 100 mg of standardized extract of the drug (Group C). All the patients took one capsule every 12 h for 8 weeks. Blood samples were withdrawn before beginning the treatment, at the fourth week and at the eighth week. The immune parameters examined were the following: chemotaxis of PMNs, phagocytosis index (PHI), phagocytosis fraction (PHF), intracellular killing, total lymphocytes (T3), T helper (T4) subset, suppressor cells (T8) subset, blastogenesis of circulating lymphocytes, natural killer-cell activity (NK). Chemotaxis proved to be enhanced (p less than 0.05) already at the fourth week in Group A as well as in Group C; the increase became even more marked (p less than 0.001) at the eight week in subjects belonging to Group C. PHI and PHF proved to be enhanced (p less than 0.05) at the eighth week in subjects of Group A; these increases were found to be higher in subjects of Group C (p less than 0.001) already starting at the fourth week. Intracellular killing was shown to be significantly increased (p less than 0.05) already at the fourth week in Groups A and C; the increase becomes highly significant in both groups (p less than 0.001) at the eighth week; however, a significant increase (p less than 0.05) at the eighth week was also noticed in the placebo group (Group B).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100738 TI - Trophoblastic factors and the maternal recognition of pregnancy in sheep and cattle. AB - The establishment of pregnancy in domestic ruminants depends upon the continued secretion of progesterone by the corpora lutea. In non-pregnant cycles the corpora lutea regress between days 12-15 after oestrus in the sheep; this process must be blocked to ensure continued exposure of the uterus to progesterone. This review discusses the evidence that embryonic products are involved in the maintenance of corpus luteum function, the identification of factors which may be responsible for this maintenance and the probable mechanism of action. The discussion centres on the recent identification of a trophoblast interferon which is thought to be the major trophoblastic factor preventing luteolysis in sheep and cattle. PMID- 2100739 TI - Effect of lactate and beta-hydroxybutyrate infusions on brain metabolism in the fetal sheep. AB - Brain uptake of substrates other than glucose has been demonstrated in neonatal but not fetal animals in vivo. This study was undertaken to investigate the ability of the fetal sheep brain to use potential alternative substrates when they were provided in increased amounts. Brain substrate uptake was measured in chronically catheterised fetal sheep during 2-h infusions of neutralised lactate (n = 12) or beta-hydroxybutyrate (n = 12). Despite large increases in fetal arterial lactate and beta-hydroxybutyrate during the respective infusions, no significant uptake of either substrate was demonstrated. However during both types of infusion, the brain arterio-venous difference for glucose decreased 30% (P less than 0.05). Since the brain arterio-venous difference for oxygen was unchanged, and blood flow to the cerebral hemispheres (measured in 11 studies) was also unchanged, the infusions appeared to cause a true decrease in brain glucose uptake. This decrease paralleled the rise in lactate concentration during lactate infusions, and the rise in lactate and butyrate concentrations during the butyrate infusions. Both substrates have metabolic actions that may inhibit brain glucose uptake. We speculate that the deleterious effects of high lactate and ketone states in the perinatal period may in part be due to inhibition of brain glucose uptake. PMID- 2100740 TI - The effects of naloxone on the changes in breathing and behaviour induced by morphine in the foetal sheep. AB - In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal. PMID- 2100741 TI - The use of two in-situ simultaneously-perfused placentas to investigate the effect of carrier proteins on linoleic and palmitic acid transfer in the guinea pig. AB - By perfusing two placentas concurrently in five animals we have found that linoleic acid is transferred across the guinea-pig placenta more readily than palmitic acid. In the in-situ perfusion this transfer is modulated by the type of albumin used in the perfusate. Removing the associated lipid from the perfusate albumin reduced the amount of non-esterified fatty acid (NEFA) transfer rather than enhanced it. Many researchers use fat free albumin as a protein carrier in in vivo and in-vitro systems, our results indicate that this may not be the most appropriate substance to use. PMID- 2100742 TI - Mechanical function and fatty acid oxidation in the neonatal pig heart with ischemia and reperfusion. AB - We investigated mechanical function and exogenous fatty acid oxidation in neonatal pig hearts subjected to ischemia, followed by reperfusion. Isolated, isovolumically-beating hearts, from pigs 12 h to 2 days of age, were perfused with an erythrocyte-enriched (hematocrit approximately 15%) solution (37 degrees C). All hearts were studied for 30 min. with a perfusion pressure of 60 mmHg (pre ischemia). One group of hearts (low-flow ischemia, N = 12) was then perfused for 30 min. with a perfusion pressure of approximately 12 mmHg. In the other group (no-flow ischemic arrest, N = 9), the perfusion pressure was zero for 30 min. Following ischemia in both groups, the perfusion pressure was restored to 60 mmHg for 40 min. (reperfusion). Pre-ischemia parameters for all hearts averaged: left ventricular peak systolic pressure, 99.0 +/- 2.0 mmHg; end diastolic pressure, 1.9 +/- 0.2 mmHg; coronary flow, 3.4 +/- 0.1 ml/min per g; myocardial oxygen consumption, 56.6 +/- 1.6 microliter/min per g and fatty acid oxidation, 33.4 +/- 1.4 nmol/min per g. During low-flow ischemia, hearts released lactate, and the corresponding parameters decreased to: 30.7 +/- 0.9 mmHg; 1.2 +/- 0.3 mmHg; 0.8 +/- 0.1 ml/min per g; 26.6 +/- 2.3 microliters/min per g and 12.9 +/- 1.1 nmol/min per g, respectively. Early in reperfusion in both groups, all parameters, except for fatty acid oxidation, exceeded pre-ischemia values, before recovering to near pre-ischemia values. Late in reperfusion, however, rates of fatty acid oxidation exceeded pre-ischemia rates by approximately 60%. Thus, the neonatal pig heart demonstrated similar recovery following 30 min of low-flow ischemia or no-flow ischemic arrest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100743 TI - Effect of exchange transfusion with a red blood cell substitute on the neonatal lung. AB - The present study was designed to evaluate the acute effects of a perfluorocarbon erythrocyte substitute on cardiopulmonary function in the newborn lamb. Isovolemic double volume exchange transfusions were performed with the perfluorocarbon emulsion (FC-43) during controlled ventilation and acid-base status. Cardiopulmonary function was determined pre (control) and post (exchange) exchange transfusion. As expected with perfluorocarbon transfusion, hematocrit decreased (from 31.3 +/- 1.35% to 6.7 +/- 0.8%, SEM, P less than 0.001) and fluorocrit increased (from 0 to 17.8 +/- 2%, P less than 0.001). These changes in blood composition were associated with a significant increase in arterial oxygen tension (from 317.0 +/- 22 mmHg to 419.0 +/- 22 mmHg, P less than 0.001) and decrease in arterial oxygen content (from 14.0 +/- 8 ml O2/dl blood + PFC to 5.4 +/- 0.3 ml O2/dl blood + PFC, P less than 0.001), A-a oxygen gradient (from 357.0 +/- 23 mmHg to 255.0 +/- 23 mmHg, P less than 0.001) and viscosity (from 3.4 +/- 0.1 cps to 2.1 +/- 0.1 cps, P less than 0.001). No significant change in lung mechanics or hemodynamics was observed. These preliminary data demonstrate cardiopulmonary and hemodynamic stability immediately following transfusion with perfluorocarbon emulsion and outline physiological responses associated with transfusion of perfluorocarbon emulsions, a potential adjunct to neonatal therapeutics. PMID- 2100744 TI - The body distribution and biological action of xenobiotics. AB - The authors explored the tissue and intracellular distribution in the body of xenobiotics (aniline-1-14C hydroclorate, dioxane-1,4-14C, toluol-1-14C, phenol-1 14C and 1,2-14C ethylene glycol) following their administration in single doses to white rats. The distribution of the tested substances in the body was correlated with their toxic effects. An analysis of distribution coefficients revealed a multifactorial nature of the distribution in the body of xenobiotics- environmental pollutants. A key role in the distribution of xenobiotics in the body is attributed to histohematic barriers which provide for the selective accumulation of xenobiotics in tissues by utilizing existing modes of active and passive membrane transport. The polytropic nature of the biological effects typical of most chemical environmental pollutants is accounted for by their multireceptor interactions in the body as well as by membrane damage resulting in the distortion of genetic information and, consequently, disorganization of metabolic processes. PMID- 2100745 TI - Bioaccumulation of metals from nickel smelter waste in P and F1 generation of exposed animals. Part III. Morphological responses. AB - Inhalation exposure experiments were conducted on a group of female adult Chinchilla rabbits placed in a field biomonitoring station located downwind from dumped nickel refinery wastes. Their F1 generation offsprings were exposed prenatally and 6 weeks postnatally. After termination of exposure, both P and F1 generation rabbits were sacrificed, their organs removed and subjected to a histologic examination using light and electron microscopy techniques. The histological responses were most marked in P generation female rabbits, namely hypertrophy of the muscle layer of pulmonary artery walls and foci of atelactasis. Electron microscopic examinations of the myocardium of chamber exposed rats revealed evidence of muscle fibre lesions at sites of intercalary discs and changes in mitochondrial structure as a result of accumulated Ni, Cr and/or other metals. Histologically remarkable was interstitial accumulation of an unidentified electron-dense crystalloid substance situated near blood capillaries and between myofibrils and collagenous fibres; this substance is believed to be a result of metal-protein interaction. The rats injected intravenously with a suspension of metal waste displayed mitochondrial lesions analogous to those observed after inhalation exposure, but no presence of the electron-dence substance could be noted. It is concluded that chronic exposure to metal waste may give rise to cardiovascular lesions. PMID- 2100746 TI - Increasing trend of hyperbilirubinemia incidence in the blood donors population. AB - Blood donors' screening has been performed during the last twenty years and it has reached a considerable post-transfusion hepatitis prevention due to disqualifying hyperbilirubinemic donors. Since 1981, AST screening has been combined with the attention paid to bilirubin--conditioned plasma colour. In the following years a steep exponential increase of hyperbilirubinemic donors incidence has been observed from 1.3% in 1983 and 1984 to 4.0% in 1988. The possibilities of a relationship to hepatitis epidemic of the years 1979-80 or to other factors are discussed. The hyperbilirubinemias are suggested to be of a posthepatitic character, produced in the unrecognised hepatitis cases who had been subclinical at the time of the epidemic. More information is expected from the development of the trend in the next years. PMID- 2100747 TI - Reinfusion of UV-irradiated blood in the treatment of infection. I. Experimental infection with staphylococci. AB - During the last 10 years, reinfusion of UV-irradiated blood has been rediscovered again as a therapeutic method suitable in the treatment of a variety of diseases. The described series of model experiments on rabbits confirm its beneficial effects in the treatment of staphylococcal infection: the control animals reinfused blood not exposed to UV radiation died all within 48 hours after injected with a suspension of live Staphylococcus aureus culture; all rabbits reinfused UV-irradiated blood (2 ml per kg body weight) survived the whole period of observation (30 days); reinfusion of UV-irradiated blood in a volume reduced to 1 ml.kg-1 body weight prolonged the animals' life-span to 96 or 120 hours. PMID- 2100748 TI - Mother's milk--unusual factor of infection transmission in a salmonellosis epidemic on a newborn ward. AB - The submitted study analyzes a salmonellosis epidemic with a nosocomial character of occurrence on newborn ward Area National Health Authority in Trencin with an unusual factor of infection transmission--mother's milk. At the same time the authors point out the possibility of inapparent disease manifestation in connection with the stopped intake of mother's milk. PMID- 2100749 TI - West Nile Complement Fixing antibodies in Nigerian domestic animals and humans. AB - A survey for West Nile Complement Fixing (CF) antibody was carried out in humans and domestic animals in Nigeria. Human sera were obtained from two communities namely Ibadan and Ogbomoso but animal sera were collected from Ibadan and Maiduguri. The overall CF antibody to West Nile virus in the two localities surveyed was 65%. Of 170 persons tested, 53% and 75% were positive in Ibadan and Ogbomoso respectively. Antibody prevalence increased with age in both communities. Tests for antibody against other flaviviruses revealed that monotypic complement fixation reactions were found frequently in young people, but broadly reacting sera were common among the older age groups. Sex distribution of West Nile CF antibody showed that 49/82 (60%) of females and 62/88 (75%) of males had West Nile CF antibody. Tests on animal sera showed that 33% contained CF antibody to West Nile virus. Prevalence of CF antibody in different animal species was 62% in camels, 4% in cattle and 0% in goats. PMID- 2100750 TI - Haemagglutination-inhibiting (HI) antibodies against strains of influenza A virus in horse and pig sera in Nigeria. AB - Sera from horses and pigs obtained from Lagos and Ibadan respectively were examined for haemagglutination-inhibiting (HI) antibodies to two strains each of H3N2 and H1N1 subtypes of influenza A virus. More horse sera had HI antibodies to the H3N2 than the H1N1 strains while pig sera reacted almost equally with strains of both subtypes. All the horse sera had HI antibodies to the two strains of H3N2 subtype (A/Mississippi/1/85 and A/Leningrad/360/86), while 87% and 14% of the horses examined were positive to A/Taiwan/1/86 and A/Chile/1/83. On the other hand HI antibody prevalence to the two subtypes in pigs are as follows, for H3N2 A/Mississippi/1/85 (86%), A/Victoria/3/75 (94%); for H1N1 A/Chile/1/83 (87%) and A/Taiwan 1/86 (79%). Analysis of the data by the Chi-square test showed significant difference between the prevalence of HI antibodies to the influenza A virus strains in horse sera examined while there was no significant difference between HI antibody prevalence to the four strains in pigs. The study shows that horses and pigs circulate influenza A virus in Nigeria and may serve as origin of human epidemics. PMID- 2100751 TI - On the methods of disinfecting bronchofibroscopes. AB - An apparatus is proposed for the wet disinfection of bronchofibroscopes which enables to wash with disinfectant solution the external surfaces of the tube and instrument channel while keeping dry the control mechanism. Several disinfecting regimens have been tested using chlorohexidine (Gibitan), benzalkonium chloride (Roccal), diocide and ethanol solutions. On experimental contamination of bronchofibroscopes with a P. aeruginosa culture effective disinfection was achieved using 0.5% aqueous and ethanol solution of chlorohexidine and 1% benzalkonium chloride solution (5-min, exposure in the circulation mode of the apparatus), 0.1% solution of diocide only produced a bactericidal effect after a 30-min, exposure. Adequate disinfection was not feasible when the endoscope was soaked in disinfectant. Similar results were obtained when bronchofibroscopes were disinfected in a clinical setup where they became contaminated with the most common pathogenic and potentially pathogenic microflora from the airways of patients suffering from purulent pulmonary diseases. PMID- 2100752 TI - Studies on immunomodulatory properties of isoniazid. IV. Effect of isoniazid on T lymphocyte activation by phorbol ester tumor promoter. AB - Human peripheral blood T cells or continuous T cell lines were treated with phorbol myristate (PMA), a direct protein kinase C activator. The effect of isoniazid on PMA-treated cells was investigated. It was found that low doses of isoniazid augmented proliferation of T cells treated with PMA or stimulated with PMA and phytohemagglutinin. Similar results were shown in the Jurkat cell line. There was no influence of isoniazid upon proliferation of PMA-treated HT-2 cells, interleukin 2-dependent cell line. The obtained results suggest that, at least one target mechanism of isoniazid is located in T cell activation pathway after protein kinase C activation. PMID- 2100753 TI - Serum protein changes in lead exposed mice infected with Hymenolepis nana. AB - Significant decrease in serum globulin took place in Hymenolepis nana mouse model treated with lead prior to infection. Decrease of alpha, beta and gamma globulins was maximum on day 4 in comparison to that of control, gradually tapering off by day 100 when suppression was minimum with the experimental values almost reaching the same level as those of the control. Thus, suppression of globulins was neither total nor permanent. PMID- 2100754 TI - A contribution to the interpretation of immunological survey records. AB - In certain infection types the use of official immunological survey figures expressed mathematically by means of exponential distribution or its distributional function may help assess the epidemiological trends in herd immunity levels. This approach to the evaluation of immunological survey records is primarily well applicable to infections that are uniform in exposure pattern, affect the entire population, and result in life-long immunity. The parameters characterizing the rise in the level of herd immunity can be determined by means of negative exponential regression. Applied to selected immunological survey data this essentially simple catalytic model of investigation may provide reliable information on the actual state of immunity in the general population, and may also help estimate its dynamics in the retrospect. PMID- 2100755 TI - Use of renal artery infusion in dogs for evaluation of diuretics. AB - In this paper we report on a series of experiments evaluating a model of renal artery infusion (RAI) as a screening technique for comparison of new diuretics, and test some assumptions underlying its use. The femoral artery and vein of Beagle dogs were catheterized for the infusion of solutions, measurement of arterial blood pressure and the sampling of arterial blood. The left kidney was isolated through a flank incision, and a 27 ga. needle, connected to PE10 tubing, was inserted into the renal artery for administration of test diuretics. Both ureters were catheterized for collection of urine. Effects on renal function were assessed during control, drug infusion, and recovery periods. At low doses, the loop diuretics, furosemide (FUR) and MK447, increased urinary excretion within the first 15 min of infusion. The effect of muzolimine, another loop diuretic, was delayed until about 45 min after initiation of infusion. Renal function returned to baseline after cessation of drug infusion. At high doses, excretion was increased by all the loop diuretics within the first 15 min of infusion. The response to muzolimine and MK447 was prolonged well into the recovery period, while that to furosemide returned promptly to baseline. Two distal diuretics, hydrochlorothiazide and amiloride, caused a significant increase in urinary excretion at both low and high doses. The magnitude of the response was significantly less than for the loop diuretics. Low doses of the loop diuretics had very little effect on the contralateral kidney; however, at high doses the excretion rate of the contralateral kidney was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100756 TI - Simple and rapid isolation of platelets using Ficoll-Uropoline cushion. AB - A simplified procedure for separation of human platelets from plasma proteins when a small volume of blood is available has been developed. In this method two centrifugations of platelets layered on Ficoll-Uropoline cushion was applied. In the first step, platelet rich plasma layered over Ficoll-Uropoline solution was centrifuged (700 g, 30 min), bounded platelets recovered with the help of HEPES buffer, and centrifuged again (1000 g, 10 min) on Ficoll-Uropoline cushion. This rapid and simple procedure yielded platelets separated from von Willebrand factor, fibrinogen and albumin, as judged by bioassay and measurement of radiolabeled plasma proteins. The obtained preparation of platelets was stable and the platelet function preserved for 3 h as evidenced by platelet aggregation and fibrinogen binding analysis. The procedure is inexpensive and convenient for small volumes of blood. PMID- 2100757 TI - Propofol in cesarean section. A pharmacokinetic and pharmacodynamic study. AB - The induction properties and pharmacokinetics of propofol, 2.5 mg/kg i.v., were studied in twelve unpremedicated healthy pregnant patients at term. The onset of anesthesia was rapid (27.7 +/- 7.3 sec) and the quality of induction, maintenance of and rapid recovery from anesthesia were clinically very acceptable. On the basis of Apgar scores and blood gas analyses of the feto-placental unit, propofol appears to be a safe alternative to other available induction agents. The pharmacokinetics of propofol in pregnant women (n = 8) were described by a high value for total body clearance (mean 2189.6 ml/min) and a short elimination half life (mean 24.1 min). There was no correlation between the pharmacokinetic parameters determined for propofol and some pharmacodynamic observations during the induction of anesthesia (n = 8), nor was there any correlation between drug levels of propofol in the feto-placental unit and blood-gas tensions and pH values or Apgar scores (n = 12). PMID- 2100758 TI - The use of human exposure and health data for improving the toxicological risk assessment of pesticides and their regulatory control. PMID- 2100759 TI - Operator contamination during pesticide application to tropical crops. AB - Investigations to determine dermal contamination of rural farmers during pesticide application to tropical crops are described. Contamination patterns and levels vary according to crop type and height, and application method. Non-toxic model pesticides and tracer dyes were applied to rice, vegetable, mango, cotton and coffee crops in the Philippines, Thailand, Tanzania and Malawi, using knapsack and ULV spinning disc sprayers. Tracer dye falling on the operator during application was measured for each type of crop sprayed. Mean gross dermal deposits of dye were: rice 97 mg/hr; mango 257 mg/hr; vegetables 103 mg/hr; cotton 220 mg/hr; coffee 95 mg/hr. The implications of these gross dermal deposit figures in relation to pesticide contamination and hazard are discussed. PMID- 2100760 TI - Field study on exposure and health effects of an organophosphate pesticide for maintaining registration in the Philippines. AB - To support the continued use and the registration of monocrotophos, a field study was conducted at Calauan, Laguna, The Philippines, to assess exposure and the resulting health risk to 21 spraymen applying monocrotophos to rice crop by knapsack spraying during 3 consecutive days. The findings of the study were as follows: exposure of uncovered hands and of the skin of the back to the concentrate was visually observed during the filling, and respectively loading operations; During spraying exposure from airborne diluted formulation occurred; in addition contamination of the lower parts of the body took place because of direct contact with the sprayed crop; Determination of the amount of the urinary metabolite dimethylphosphate excreted in 24 hours urine samples demonstrated absorption of monocrotophos into the body of the spraymen. The half-life of elimination of the urinary metabolite from the body was on average 18 hours; No clinically significant inhibitions of whole blood or red blood cell cholinesterase activities were found, i.e., 30% below baseline values. However, 8 of 21 spraymen had plasma cholinesterase levels below 50% of baseline values;--No acute adverse health effects associated with the application of monocrotophos were observed, which was in accordance with the absence of clinically significant cholinesterase depressions. The conclusion of the study was that the use of monocrotophos under prevailing typical conditions in the Philippines, which varies from a frequency of one application per season to a maximum of 3 applications each on 3 consecutive days per week, and where label safety instructions are not necessarily observed, is not expected to pose an acute health risk under the prevailing conditions and practices, which includes filling, spraying and cleaning activities. From the experience in this study it is clear that proper spraying technique and adequate use of personal protection will significantly reduce exposure. As such a reduction is highly recommendable, advice on proper spray procedures and adequate personal protection has been reinforced. PMID- 2100761 TI - Gauging pesticide exposure of handlers (mixer/loaders/applicators) and harvesters in California agriculture. AB - Agricultural workers acquire pesticide exposures as a function of the properties of the product, crop, and work task. Mixer/Loaders and Applicators have greater exposure potential than other workers since concentrated formulations are handled during preparation and application of spray mixes. Exposures can be estimated using passive dosimetry and biological monitoring. Measured exposures are invariably less than estimates derived from surrogate data due to a series of conservative "worst case" assumptions and exposure estimates derived from small portions of the work day. Data have also been collected to estimate the exposure potentials of harvesters. We are establishing a set of empirical transfer factors (cm2/h) that can be used to estimate daily harvester exposure (transfer factor x dislodgeable foliar residue x hours). These estimates are important to current efforts to establish exposure-based reentry intervals to protect against acute and chronic toxicity. PMID- 2100762 TI - Field evaluation of protective equipment for pesticide operators in a tropical climate. AB - In order to extend the practical advice and information on personal protection when using pesticides in tropical climates, a GIFAP-FAO Working Group carried out a study on protective equipment worn by pesticide workers in hot and humid conditions in Thailand. Items assessed included protective garments worn by workers mixing and loading the organophosphorus insecticide formulation Tamaron and by spraymen applying the diluted formulation for several hours per day to a cotton crop with knapsack sprayers. The mixer-loaders also wore nitrile rubber gloves and a faceshield. The protective garments were made up of two pieces, an upper garment of a double apron design and separate trousers. Garments made up of different materials were assessed for their acceptability to the workers, their comfort and durability and their protectiveness against the insecticide. As a result of the study it is considered that cotton protective garments are appropriate for pesticide workers in these conditions if additional protection is necessary. The nitrile rubber gloves and faceshield were also found to be suitable for mixer-loaders in these circumstances. It is emphasized that the effective use of protective equipment must go hand in hand with safe handling precautions and the adoption of good personal hygiene. PMID- 2100763 TI - The International Centre for Pesticide Safety. AB - The International Centre for Pesticide Safety (ICPS) was inaugurated in March 1990. Coordinated by the World Health Organization (WHO) and in collaboration with research and university institutions, the Centre operates in the following areas of activity: information and documentation on pesticide toxicity; epidemiological, toxicological and clinical research; training and education; laboratory research. ICPS is also a centre of meetings and courses on permanent education. This paper reports on the activities carried out so far and on the future programmes of ICPS. PMID- 2100764 TI - Epidemiologic study for the evaluation of the cancerogenic risk associated with pesticides. AB - A begun started Italian multicentric hospital-based case-control study aimed at detecting carcinogenic risk associated with pesticides exposure is presented. During a 2 year period, incident cases of cancer of various sites in adults of both sexes will be identified in five hospitals used by residents of five Italian rural areas (Asti, Imola, Pescia, Pistoia, Grosseto). Selected sites include the following: lip, oral cavity and oropharynx, oesophagus, stomach, colon-rectum, liver, biliary ducts, pancreas, larynx, lung, soft tissue, skin melanoma, skin other than melanoma, breast, uterus, ovary, prostate, bladder, kidney, thyroid, and lymphoid tissue. Trained personnel will interview patients about their total work experience, with special emphasis on activities in agriculture. Other relevant information to be collected includes pathological anamnesis and smoking habits. A team of coders will analyse the occupational histories using an a priori job-exposures matrix (JEM). The JEM will be specific with respect to type of agricultural production, calendar years, geographic location and pesticides. Each cancer site will be compared with a selected pool of the other sites. This investigation is expected to provide information on a range of associations between cancer of various sites and individual pesticides or mixed exposures. The study can be seen as a pilot study which could be replicated in other areas. PMID- 2100765 TI - Mortality study of Canadian male farm operators: cancer mortality and agricultural practices in Saskatchewan. AB - The present investigation involved an analysis of approximately 70,000 male Saskatchewan farm operators, a subset of the 365,000 Canadian farm operators to be investigated in the Canadian Farm Operator Mortality Study. The results of the Saskatchewan analysis indicate that during the interval studied, overall mortality among Saskatchewan farmers was 25% lower than that for all Saskatchewan men, and that, during the same time interval, the risk of death from all types of cancer was also about 25% lower among Saskatchewan farmers than to all Saskatchewan men. Although the present study indicates that overall mortality of death from cancer was 25% lower among Saskatchewan male farmers, there was a relationship between non-Hodgkin's lymphoma mortality and acres sprayed for weeds; a similar risk relationship between expenditures on fuel oil and risk of death from non-Hodgkin's lymphoma was also evident. The magnitude of risk for Saskatchewan farmers is probably greater than that reflected in the estimates in this study, due to the likelihood of misclassification of exposure. There is a particular need for further studies in this area to improve the quantification of farming-related exposures, and to study the exposure history of individuals who develop non-Hodgkin's lymphoma. PMID- 2100766 TI - Italian multicentre case-control study of hematolymphopoietic malignancies. AB - Exposures to organic solvents (including benzene), ionizing radiation and low frequency electromagnetic fields have been suggested as risk factors for leukemias in adults. Exposure to herbicides of the phenoxyacid variety (2, 4, 5 T; 2, 4-D) has been reported to be associated with an increased risk of non Hodgkin's lymphomas. In addition several studies have suggested that agricultural workers have an excess risk of hematolymphopoietic malignancies, although no specific agent has yet been identified. Italy is particularly attractive for investigating further these associations, because: a) there is a high prevalence of exposure to solvents in industrial areas (estimated to be 10-16% in the province of Torino, Varese and Florence), and a high prevalence of exposure to herbicides (including phenoxyacides) in agricultural areas; b) there is also considerable extra-occupational exposure to solvents and pesticides; c) competent groups of hematologists exist in several towns, using advanced diagnostic techniques including cytogenetics. We propose therefore to conduct a multicenter population-based case-control study in 11 italian areas, chosen on the basis of a high exposure prevalence. In three years, we intend to interview approximately 1100 cases of leukemia, 1900 cases of lymphoma (Hodgkin and non-Hodgkin) and 400 cases of myeloma; 1900 randomly selected individuals, residents of the same areas, will serve as a population control group. Cases will be all those occurring in the study period among residents of the 11 areas, newly diagnosed. Particular care will be dedicated to diagnostic aspects, including B- and T- cell characterization. Cases and controls will be blindly interviewed by trained personnel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100767 TI - Health effects of pesticides on female beet growers. AB - The working conditions of female beet growers and their health effects were studied. Dust, chemical substances, physical strain and the forced working posture were among the occupational factors producing adverse health effects. Contact with pesticides is believed to be the major factor in the development of chronic pathology and temporary disability among female beet-growers. There is a need to promote a system of preventive measures, including comprehensive biological monitoring and control of pesticide concentrations in the environment. PMID- 2100768 TI - Experience of health status surveillance of pesticide workers in Hungary. AB - The authors studied potential dermal exposure in 26 men and also conducted epidemiological studies in three southeastern agricultural counties in Hungary covering 189 men working with pesticides in plant protection indoors and in the fields, and in 16 women in contact with these compounds. There were no acute intoxications, nor were there any alterations in routine clinical and laboratory tests. For early detection of hidden damage the authors used examination of the chromosomes: the rate of numerical chromosome aberrations was increased due to increase of hypodiploid cells in the exposed. The probability of chromosome damage was also demonstrated by the tests conducted in the few women tested. In previous studies on the immune functions in some of the men tested the immunological tests proved to be positive. Though changes might be induced also by other factors, the authors believe it is important to frequently screen the exposed population in the manner described. PMID- 2100769 TI - Problems encountered in the design of epidemiologic studies of cancer in pesticide users. AB - Epidemiologic studies of cancer in pesticide users suffer from three main difficulties: lack of appropriate controls, exposure ascertainment, and exposure to multiple pesticides. Principles of control selection are discussed in the context of cohort and case-control studies. Residence on a farm is associated with unique dietary and lifestyle factors which are important to account for in case-control studies of pesticides users on farms. Exposure ascertainment methods include information collected from job descriptions, interviews, pesticide suppliers, expert panels, application records, passive dosimetry, and biological monitoring. Sensitive methods based on cell receptor-pesticide complexes have been proposed, but have not yet been validated and field tested as methods of quantitative exposure assessment. Examination of studies which successfully helped demonstrate cancer causation is suggested as a means of determining which epidemiologic methods are most fruitful and efficient at identifying human carcinogens. PMID- 2100770 TI - Health effects of pesticides in the flower-bulb culture in Holland. AB - In a comprehensive project the health risk for workers using pesticides in the flower-bulb culture was addressed in several studies regarding biological monitoring, occupational hygiene and health effects. With respect to biological monitoring, methods were developed for the analysis of metabolites in urine of captan, pirimicarb, zineb and maneb and the soil fumigant dichloropropene. For dichloropropene in a field study a clear relationship was found between the external personal exposure and the excretion of two metabolites (mercapturic acids) in urine. The application technique distinctly influenced the extent of exposure. For the other substances preliminary measurements were performed in the urine of exposed workers; for captan and pirimicarb the methods are promising for further studies of the uptake of these substances under working conditions. In an occupational hygiene study, the dermal exposure due to different application techniques used in crop protection and bulb disinfection was investigated. This resulted in method specific exposure values (grams/field area of bulbs) that showed large differences between the techniques. These exposure values in combination with information on the type of techniques used, the treated area and the frequency of application were used to calculate a personal exposure index (grams/working life); this is an estimate of the potential (external) exposure of individual workers. In an effect study 137 workers who applied pesticides for more than 10 years (average 20 years) in at least bulb disinfection and crop protection (the most important area's of exposure for the growers) were compared to 73 controls. Tests for autonomic and peripheral nerve functions including the distribution of conduction velocities and refractory periods, were applied as well as computerized neurobehavioral tests and electro-encephalography. Significant effects were found on peripheral nerve function parameters, on measures of attention and perceptual coding and on the amount of beta-activity in the EEG; the data suggest that for the majority of subjects these effects are small. No effects were found on liver and renal function and no difference in the prevalence of symptoms that might be ascribed to the usage of pesticides. In a number of exposed workers a cutaneous allergy to pesticides was found. Based on this study, measures are recommended to diminish effectively the exposure to pesticides in this culture. PMID- 2100771 TI - [Sorption detoxification in the combined therapy of chemical eye burns]. AB - Comparative assessment of results after treatment of 90 patients with chemical burns of moderate and severe degrees was made using a sorption (103 eyes) and traditional (47 eyes) methods of treatment. The sorption method included the usage of ocular medicinal ionometabolic insertions and a 10% medicinal gelatine that are able to eliminate ions from the burning substance and toxic product formed in the eye due to burns. As a result of treatment, the sorption method allowed to obtain higher functional results, to achieve a shorter time for the patient's stay in the hospital, by 11.2 bed-days, on the average. Thanks to the sorption method introduced into the clinical practice the economic effect made up about 50,000 rubles yearly. PMID- 2100772 TI - [The diagnosis and treatment of the dry eye syndrome of burn etiology]. AB - In 14 patients (22 eyes) with a burn disease of the eye, a "dry eyes" syndrome was diagnosed. Its diagnostic signs were simultaneous reduction of physiologic tear production to 7 mm and the shortening of time of the tear film break to 8 sec. and lower. The mentioned values were indications to instillations of a preparation, a so-called "artificial tears" (a 6% water solution of polyvinylpyrolidone). Such a therapy allowed to increase the volume of fluid in the conjunctival sac and the stability of tear film as well as in 87.5% of patients to remarkably reduce subjective disorders. PMID- 2100773 TI - [The nature and results of the treatment of eye burns based on data from the Chernovtsy Province Eye Trauma Center]. AB - The character and results of eye burn treatment have been studied in 226 patients (307 eyes) aged from 10 to 80 years. The analysis of the character of eye burns has shown that the overwhelming majority of them were chemical ones (80.54%), of them 50% being alkaline. As to degree of severity, burns of moderate degree predominated (58.74%). The greatest part of the sufferers had everyday-life burns (67.7%). Results of treatment depended, mainly, on the severity of the burn. By the results of treatment, the patients were divided into 4 groups: group I included patients with total restoration of corneal transparency, who can return to their former labor activity; group-II patients with partially lost visual functions on account of remained, moderately expressed cicatricial opacifications of the cornea, who in future require repeated courses of resolving therapy; group III patients with a remarkable loss of visual functions on account of coarse cicatricial opacifications of the cornea, who in future require surgical treatment--keratoplasty, keratoprosthesing and other surgical interventions; group IV-patients with total restoration of corneal transparency after treatment, but with insufficiently high visual acuity because of associated changes in the optic media and the eye fundus (beginning cataract, macular dystrophy, etc.), who require dispensary observation and treatment of associated diseases. PMID- 2100774 TI - [The use of eye films with apilac in treating corneal burns]. AB - Clinical trial of eye films with apilac used in complex treatment of 47 patients with thermic and chemical corneal burns has shown acceleration of corneal epithelialization in 37 (78.7%) patients as compared with the control group. Rise of visual acuity from 0.1-0.4 to 0.5-0.9 was recorded in patients with burns of a moderate degree and from 0.005-0.02 to 0.03-0.07--with severe eye burns. Better results after apilac therapy were observed when the films were used in combination with low-intensity helium-neon laser radiation of the cornea. PMID- 2100775 TI - [Changes in the T-lymphocyte subpopulations in patients with severe eye burns]. AB - The paper analyses results of clinico-immunologic examinations of patients with severe eye burns. Immunologic investigations were made on a laser cytofluorometer "SPECTRUM II" (USA) using monoclonal antibodies OCT-3, OCT-4, OCT-8, OCT-11. Correlation between changes of the level of T-lymphocytes subpopulation and the severity and outcome of the trauma was established and prognostic significance of immunoregulatory index OCT-4/OCT-8 proved. The necessity of selective aimed immunocorrection is substantiated. PMID- 2100776 TI - [Experimental validation of the use of RNA hydrolysate (ENKAD) in chemical burns of the cornea]. AB - The influence of ENKAD on the course of a severe alkaline burn of the cornea was studied in 158 rabbits (316 eyes). Cytochemically, regularity in correlations of separate amino acids: cystin, cysteine, arginine and glutaminic acid in cellular proteins of the intact cornea was established and their disorder in dynamics of the burn process is shown. Comparative assessment of therapeutic effectiveness of ultrasound, applications, subconjunctival injections and phonophoresis of ENKAD has shown that a combined usage of ultrasound and ENKAD has the most expressed positive action on the course of the burn process of the corneal burn, such as acceleration of corneal epithelialization that accomplished, on the average, by the 9.3 +/- 0.3 day (in the control--by the 20.8 +/- 1.8 day), rapid disappearance of its perifocal edema--11.05 +/- 0.7 (in the control - 29.7 +/- 1.1) day, better outcomes after the burn (in 37.5% of cases superficial limited opacifications were formed, in the control--in 7.1%). One of the factors of therapeutic action of ENKAD phonophoresis is its normalizing influence on disturbed correlation of amino acids in proteins. The results obtained allow to recommend to include ENKAD phonophoresis into a complex treatment of patients with eye burns. PMID- 2100777 TI - [A new pyrimidine-series preparation in the treatment of experimental chemical eye burns]. AB - The effectiveness of a substance of a group of pyrimidine derivatives LUS-3 has been studied in 87 rabbits (174 eyes) with chemical burns of the cornea of degree III. In parallel series of experiments, its action was compared with one of traditional methods of treatment of eye burns using sodium sulfacetamide in combination with subconjunctival injections of autologous blood with penicillin as well as with a pyrimidine derivative--methyluracil. The assessment of the effectiveness of the preparations was made by the picture of the clinical course as well as by data of histologic investigations. The results obtained have shown a pronounced effectiveness of the preparation LUS-3: it accelerated regenerative processes, prevented development of secondary infection, and, as a result, conditioned formation of low-intensive opacifications of the cornea. PMID- 2100778 TI - [The effect of thymogen on the cell division processes in the corneal epithelium under physiological conditions and in an experimental thermal burn]. AB - Experimental studies of the influence of a new pharmacologic preparation thymogene on the processes of cellular multiplication of the corneal epithelium in physiologic conditions and thermic burn of the eye in 140 rats. (280 eyes) have shown that in intact animals the preparation produces DNA synthesis in both systemic and local usage, that is most expressed by the 3d-5th day after its administration. The study of the influence of thymogene on reparative processes in rats with corneal burns has shown that administration of the preparation stimulates processes of cellular population in the corneal epithelium both in the early period (on the 3d day) and by the 14th day after burn trauma. This allows to consider thymogene a perspective preparation for a quicker healing of the cornea after burn trauma. PMID- 2100779 TI - [Tear enzymes in the treatment of an experimental alkaline corneal burn with gordox]. AB - The study of the influence of hordox, in treatment of experimental alkaline burn of the cornea, on the activity of trypsin-like proteases, elastases, callicreine, beta-N-acetylglucosaminidase and beta-glucuronidase in a tear fluid has shown that activity of these enzymes in a tear after burn remarkably increases, especially within first 24 hours and at the end of the second week after burn. In treatment by hordox, the activity of all enzymes in the tear, except elastase, reduces as compared with untreated animals, that speaks about antiinflammatory action of the preparation. On the basis of the data obtained it is suggested that investigation of hydrolytic enzymes in a tear can serve as a criterion for aimed correction of proteolysis in inflammatory processes in the cornea. PMID- 2100780 TI - [The clinico-morphological validation of the pathogenetic treatment of industrial eye burns]. AB - The paper generalizes and analyses experimental results obtained in 60 eyes of 30 rabbits after induced burn by means of epichlorhydrine that is widely used in chemical industry and produces industrial burns of the eye in 20% of all burns in the town of Sumgait. Clinico-morphologic researches allowed to reveal peculiarities of pathogenesis of severe eye burns produced by epichlorhydrine causing toxic lesions of the iris and to substantiate effectiveness of hordox used in such cases, that has not only antiproteolytic, but also antiinflammatory, cytotoxic action on the burn process. PMID- 2100781 TI - [The functional characteristics of the eye vessels in glaucoma and suspect glaucoma]. AB - The paper analyses results after examination of the functional state of eye vessels in 92 patients (117 eyes) with initial stage of glaucoma and 44 persons (55 eyes) with suspected glaucoma. A control group included 31 patients (41 eyes) without any eye pathology. For assessment of the functional state of eye vessels, cryorheographic test was used. Main types and variants of neurovascular reactions of the eye were determined. Reduced vascular tonus was recorded in most of the subjects. Glaucomatous, patients showed predominantly organic changes in the vascular bed of the eye. In persons with suspected glaucoma, the incidence of functional and organic changes of the vessels was approximately the same. In healthy persons, functional changes were observed more frequently. A conclusion is made that the functional state of the vascular bed of the eye should be considered when prescribing medicamentous treatment for glaucomatous patients. PMID- 2100782 TI - [Visual evoked potentials to a light flash in patients with optic nerve atrophy]. AB - Informativeness of different methods used for registration of optic generated potentials in response to light flash (FOP) has been studied in 27 healthy persons and 21 patients (32 eyes) with partial atrophy of the optic nerve. It is shown that the most informative one for diagnosing optic nerve atrophy and determining visual acuity in such patients is a method of investigation of the critical incidence of rythm reproduction of FOP light flickerings. Considering the complexity and difficulty of the mentioned method for its practical usage, a simplified method is proposed; a registration of FOP of a stable state with the incidence of stimulations of 33 Hz, that allows to detect cases of pathology with visual acuity not less than 0.2. PMID- 2100783 TI - [The laser surgery of cystic filtration pads]. AB - The paper describes results after treatment of 12 patients with cystic filtration cushions formed after antiglaucomatous operations. Two methods were used: introduction, into the cystic filtration cavity, of either autologous blood or serum of autologous blood stained by sodium fluorescein solution with subsequent coagulation by argon laser radiation, energy 0.2-0.4 wt, spot diameter 200-500 mem, exposition time 0.2-0.3 sec. The number of applied coagula depended on the size of a cystic filtration cushion. The results of treatment, followed up within a year, have shown formation of a filtration cushion of a vague type, appearance of stabilization of intraocular pressure and visual functions in all patients. PMID- 2100784 TI - [Arc-wedge keratoplasty as a method for correcting astigmatism]. AB - In view of low effectiveness of optic correction of astigmatism a problem of its surgical correction becomes urging. A new operation for correction of astigmatism -arc wedge-keratoplasty, worked out by the authors, was made in 19 eyes with mixed and complex myopic astigmatism. Before operation the degree of astigmatism was, on the average, 6.8 +/- 2.11D (4.5-14.0), after operation--2.2 +/- 0.18D (0.18-5.5). The refractive effect made up, on the average, 4.6D (from 2.0 to 12.5). A change of a refractive power of the cornea was seen in both main meridians. The follow-up period ranged from 6 months to 4 years. The operation is highly effective and less traumatic than the known ones because only two notches are made and the central free zone not less than of 5 mm is preserved. A conclusion is made that operation of arc wedge-keratoplasty is advisable for correction of mixed astigmatism. PMID- 2100785 TI - [The graphic representation of the temperature field of the skin surface in the orbital area]. AB - The paper describes results of researches on the possibility of graphic presentation of a temperature field of skin surface of the orbital area. A method of liquid crystal thermography and electron thermometry was used for examination of 30 patients with practically healthy eyes. It was shown that graphic presentation of data of liquid crystal thermography and electron thermometry remarkably facilitates documentation and analysis of the results obtained. PMID- 2100786 TI - [The structural and blood supply characteristics of the optic disk]. PMID- 2100787 TI - [Alveolar soft part sarcoma--case report]. AB - A case of alveolar soft part sarcoma has been described in a 12-year from old girl. Immunohistochemical reactions on paraffin sections from the tumour were directed towards the presence of desmin , vimentin and neurospecific enolase. Positive reaction to desmin and neurospecific enolase was found in neoplastic cells. PMID- 2100788 TI - [Barrett esophagus]. PMID- 2100789 TI - [Immunohistochemical diagnosis of soft tissue neoplasms]. PMID- 2100790 TI - [The role of determining the levels of bombesin and gamma-enolase in differential diagnosis of bronchogenic carcinoma of the lung]. PMID- 2100791 TI - [Immunocytochemical evaluation of estrogen receptors in histological specimens of primary breast cancer]. AB - Immunocytochemical methods (ER-ICA) by using monoclonal antibodies were applied to determine the presence of estrogen receptors (ER) in 44 primary breast cancers in women. Of this 48% of the tumours were classified as receptor positive. In these tumours the nuclei had a clearly positive heterogenous colouration. In three cases a positive reaction was also found in benign epithelial cells of the breast. ER determinations by ER-ICA method were compared with quantitative analysis carried out by using radioligand and immunoenzymatic methods. There was a strong correlation between immunocytochemical ER evaluations and quantitative methods. We also found a correlation of the menopause state and patients age and ER content. PMID- 2100792 TI - [Morphological and clinical evaluation of non-epithelial and mixed neoplasms of the female reproductive organs. II. Leiomyosarcoma]. AB - Among 12886 malignant neoplasms of female sex organ 34 leiomyosarcoma were found. Average age of suffering women was 50 years. Metrorrhagia and lower abdominal pain were most common symptoms reported. Surgical treatment was supplemented with radiotherapy. Significant impact on prognosis showed: number of mitoses, number of bizarre and giant cells, massive necrosis and hyalinization. Efficient early diagnosis these neoplasms still awaits improvement. PMID- 2100793 TI - [Effects of D-penicillamine and encorton on the fibrotic processes in experimental liver cirrhosis in rats]. AB - The aim of the study was to evaluate the effects of D-penicillamine (cuprenil), encorton and both drugs in combination on fibrotic processes in the rat liver damaged by chronic use of CCl4. The studies comprised 80 white Wistar rats divided into 8 experimental groups. Group I receiving every day oral methylocellulose for 12 weeks was a control group. In group II the rats were given only CCl4 for 12 weeks. In the remaining experimental groups beside CCl4 the animals received drugs in various doses and for various periods. At 12 weeks all animals were killed and post-mortem studies were performed. The liver sections for histopathological studies were fixed in 10% buffered formaline. Paraffin specimens were stained with hematoxylin and eosine. Colour reactions to collagen fibers were performed by using Heidenhein's method and to reticuline fibers by Gomori's method. In the assessment of the severity of fatty degeneration, inflammatory infiltrates and fibrosis the 3-point scale was used, ranging from + for minor changes, ++ for moderate changes, for severe changes, and 0 for no changes. Morphological analysis of the liver showed that chronic administration of CCl4 produced an experimental model of cirrhosis of the liver in rats. Concomitant use of CCl4 and cuprenil revealed its inhibiting action on the fibrotic process in the rats' liver. Inhibition of fibrosis varied and was related to the dose and time of its action. The most optimal was a low dose, 10 mg kg of body weight, whereas a double dose used during the experiment appeared less favourable. Similarly less effective action was exhibited after encorton. After combined use of both drugs the inhibitory effect was negligible. In addition hepatotoxic effects were found manifested by marked fatty degeneration of hepatocytes. PMID- 2100794 TI - [Morphological studies of the effects of protein-free diet and branched-chain amino acids (aminosteril-hepa (Frasenius)) on experimental thioacetamide-induced liver damage]. AB - The studies were performed in two groups of rats in which experimental hepatic encephalopathy was induced with tioacetamide++. One group of rats on protein-free diet was given intraperitoneally a mixture of amino-acids (Aminosteril-Hepa), the other one was given proteins in the diet in a dose 1 g per kg of body weight. Histological and histochemical studies revealed that free-protein diet with a mixture of aliphatic polybranched amino-acids (Aminosteril-Hepa) inhibited hepatotoxic thioacetamide+ action on the rat liver. PMID- 2100795 TI - [Morphological picture of the lateral cruciate ligament of the rabbit knee after its intra-articular transposition]. AB - The aim of the study was to evaluate morphological changes occurring in an experimentally reconstructed anterior cruciate ligament. Experimental studies concerned 20 New Zealand rabbits. We showed the phasic character of morphological changes within the intra-articularly transposed ligament. The phase of transplant revascularization and maturation of collagen fibers were considered the most significant. PMID- 2100796 TI - [Topics of research in the field of preparation, modification and preservation of human blood cells as reflected by the international patent literature]. PMID- 2100797 TI - [New heterocyclic systems for thiophene-2-thiolates--synthesis and biological activity]. AB - Dicyanketendithiolae reacts with equimolar amounts of halogenmethans, substituted with electron withdrawing groups, to give thiophene-2-thiolates. These compounds are used for the preparation of thieno[2,3-b]thiophenes, including several functional groups in 2- and 5-position. Anellation of 1,3-oxazin-, pyrimidin-, 1,2,3-triazin- or 1,4-oxazepin-cycles give hitherto unknown tri- and tetracyclic ring systems. Some of synthetised compounds show biological activity. PMID- 2100798 TI - Kinetic analysis of drug release from hydrogels containing amphoteric surfactants. AB - A one compartment open model was used in order to describe chloramphenicol release from hydrogels containing amphoteric surfactants as gelling agents. Such interpretation seems to be more profitable than that based on Higuchi's root square equation. Using the proposed model it is possible to consider that drug release takes place from the water phase near the surface of membrane, rather than from the micellar phase in which drug seems to be immobilized. PMID- 2100799 TI - [The lymphocyte transformation test using mononuclear cells of elderly humans as a suitable in vitro method for testing of structure activity relationships of splenin peptides]. AB - More and more new immunostimulatory substances are developed. Besides old and new drugs have to be examined with regard to their side effects. Hence it follows demands for effective test possibilities. The lymphocyte transformation test with mononuclear cells of old men is a suitable in vitro method for testing of substances with thymic hormone-like activity in order to investigate the structure-effect-relationships. Thymopentin, human splenopentin and human diacetyl-splenopentin increase the phytohaemagglutinin induced lymphocyte transformation, on the other hand in the case of bovine splenopentin and human splenotritin this effect was not observed. By means of a patient with hypogammaglobulinaemia is demonstrated that the lymphocyte transformation test could also be a suitable method for the estimation of pharmacodynamics such peptides after in vivo treatment. PMID- 2100800 TI - Oxidation phenotyping with debrisoquine in Germany (East). AB - An hplc method is described which determines debrisoquine and its metabolite, 4 hydroxydebrisoquine, quantitatively after conversion of the guanidine moieties into the corresponding pyrimidines. Sensitivity, precision, and accuracy have been sufficient enough for the reliable hydroxylation phenotyping of 145 non related healthy volunteers (64 males, 81 females, 31-80 years). 17 (11%) were poor metabolizers of debrisoquine (gene frequency: 34.2%). PMID- 2100801 TI - [The pharmacologic activity of p-substituted DL-2-phenylglycine octyl esters]. AB - DL-2-phenylglycine octyl ester has antiphlogistic, analgesic and spasmolytic activities as shown in different animal models. The antiphlogistic effectiveness is changed only a little by the p-substitution at the phenyl ring, whereas the analgesic action is markedly influenced. Most of the substituted compounds are significantly more active than the unsubstituted ester. DL-2 (benzyloxyphenyl)glycine octyl ester is the most active compound, it has furthermore the highest therapeutic quotient. Using the i.p. application its efficacy exceeds that of acetylsalicylic acid, phenylbutazone and indometacin, respectively. The spasmolytic activity is differently changed by the substituents. The most active ester, DL-2-(p-methoxyphenyl)glycine octyl ester, is about two times more active than papaverine. In histamine induced spasm the effectiveness is low compared with the specific antagonist mepyramine. The results obtained show that the activities of the p-substituted DL-2-phenylglycine octyl esters are different with regard to the three investigated pharmacological properties. PMID- 2100802 TI - [Research schools in pharmacy. 5: Alexander Tschirch (1856-1939) and his students]. AB - Alexander Tschirch was one of the most important teachers of pharmacy. In 1890 he was appointed Professor of Pharmacy and Pharmacognosy at Bern and he was a good director of his institute. The scientific programme is represented by 21 books, 388 papers and 158 dissertations. The main topics were investigations of plants (phytochemical) and researchs for pharmacopoeias. Tschirch had 2300 Students, 158 made their doctor-graduate and 11 are becoming professor. The research conditions in the pharmaceutical institute Bern were good and the research school of Tschirch has an important public and social recognition, also Tschirchs work provided the bases of the modern phytochemical research of plants. PMID- 2100803 TI - Noninvasive in vivo detection of a fluorinated neuroleptic in the human brain by 19F nuclear magnetic resonance spectroscopy. AB - A fluorinated long-acting neuroleptic (fluphenazine decanoate) was detected in the human brain by fluorine nuclear magnetic resonance spectroscopy (MRS). The MRS system used had a 3 Tesla magnetic field, corresponding to a frequency of 118 MHz for the fluorine nucleus (Bruker Medspec 3 Tesla, 60-cm magnet bore width). The spectra were obtained with a surface coil having a 10-cm diameter, which was centered alternatively on the frontal lobe and basal ganglia, and on the occipital lobe. The impregnation and elimination kinetics of fluphenazine were monitored during three sessions (4 hours, 5 days, and 11 days after injection of the compound). This technique can be usefully applied to the in vivo study of the pharmacokinetics and site of action of psychiatric compounds in man. PMID- 2100804 TI - A quantitative analysis of CT and cognitive measures in normal aging and Alzheimer's disease. AB - Patients with presumptive Alzheimer's disease (AD) and healthy community volunteers received computed tomographic (CT) brain scans and cognitive tests. The CT scans were quantitatively analyzed with a semiautomated thresholding technique to derive volumetric measures of cerebrospinal fluid (CSF)-to-tissue ratios in six regions of interest (ROIs): lateral ventricles; vertex sulci, frontal sulci, Sylvian fissures, parieto-occipital sulci, and third ventricle. Regression analysis was performed on CT data from 85 older volunteers (ages 51 82) to generate age norms for each ROI. Within this group, tissue loss, as measured by the % CSF in each ROI, was highly correlated with age, although each ROI showed different rates of change over age. For all ROIs, the AD group had significantly more tissue loss than expected in normal aging. In addition, AD patients with a presenescent onset (before age 65) tended to have greater vertex sulcal and frontal sulcal tissue reduction than AD patients with a senescent onset (age 65 or after). When regional tissue reduction, corrected for age, was correlated with cognitive test scores, two sets of double dissociations emerged within the AD group: large CT z scores (i.e., decreased tissue and increased CSF) of frontal sulci, but not of the third ventricle, correlated with low Comprehension and Boston Naming Test scores, whereas large CT z scores of the third ventricle, but not of the frontal sulci, correlated with low scores on Digit Symbol and Picture Arrangement. These results suggest that heterogeneity of structural and functional integrity exists among patients with AD. PMID- 2100805 TI - Reduction in temporal lobe size in siblings with schizophrenia: a magnetic resonance imaging study. AB - Twenty-eight individuals with familial schizophrenia, from 16 unrelated families (12 sibling pairs and 4 individuals whose siblings refused scanning), and 21 normal control subjects were examined by cerebral magnetic resonance imaging (MRI). Measurements of the cerebrum, temporal lobes, and cerebral lateral ventricles were obtained using consecutive coronal sections containing these structures. Temporal lobe volume was significantly decreased by approximately 10% in these early onset schizophrenic siblings compared with normal controls. These findings add to recent post-mortem and neuroradiological evidence for morphological alteration in the temporal lobes in schizophrenia. PMID- 2100806 TI - Astrocytosis in the molecular layer of the dentate gyrus: a study in Alzheimer's disease and schizophrenia. AB - Recently, several authors have claimed prominent abnormalities in the entorhinal cortex of both patients with Alzheimer's disease (AD) and schizophrenia. The entorhinal cortex is the origin of the perforant pathway, a major input to granule cells of the dentate gyrus of the hippocampus. The present study explored the possibility of a lesion in the entorhinal cortex of both AD and schizophrenic patients by quantitating astrocytic markers within the terminal fields of the perforant pathway. An increase in fibrillary astrocytes was found in half (3/6) of the AD patients while none of the schizophrenic (n = 6) or control (n = 7) brains exhibited gliosis. Since the redistribution and hyperplasia of astrocytes within the molecular layer of the partially deafferented dentate gyrus depend on the chronicity of the entorhinal lesion, the abnormalities observed in AD patients are consistent with the progressive course of the illness. Furthermore, the presence of gliosis in the subiculum of three out of six AD patients suggested pathology secondary to projections from the entorhinal region, amygdala, or prepyriform cortex. The absence of similar changes in schizophrenic patients does not disprove previous claims of entorhinal pathology but suggests that the lesion, if it exists, is either static in nature or occurred long before death. PMID- 2100807 TI - Quantitative EEG correlates of crack cocaine dependence. AB - Evidence for a distinctive syndrome of neuroadaptation in cocaine dependence has accumulated from behavioral, neurophysiological, and preclinical and clinical pharmacological studies. The authors report on the results of a preliminary investigation of the quantitative electroencephalographic (QEEG) correlates of severe DSM-III-R crack cocaine dependence in seven patients abstinent from cocaine for 1 to 68 days. The major QEEG finding was increased absolute and relative alpha power. Increased alpha power has also been reported in multiple previous studies of depressed patients. This series of crack-dependent patients showed significant depressive morbidity; four patients attempted suicide subsequent to initiating their use of crack and the group mean (+/- SD) Beck Depression Scale score was 18.9 (+/- 6.5). These results complement other studies that support the concept of neuroadaptation to chronic cocaine exposure. Prospective studies correlating QEEG measures with subsequent response to pharmacological interventions for cocaine dependence should be considered. PMID- 2100808 TI - [Subacute sclerosing panencephalitis (SSPE) in Poland 1987-1989. Stage IV of the epidemiological studies]. AB - In the years 1987-1989 111 patients of SSPE who react positively to laboratory tests were found in Poland. The incidence rate of the disease was in 1987-1.30; in 1980-0.98 and in 1989-0.66 per million inhabitants (in the years 1984-1986 the incidence of SSPE was respectively 1.22; 1.05 and 0.9 per million). The authors observed a shift in the incidence peak of SSPE from the age group 8-9 years in 1977-1983 and 10-12 years in 1984-1986 to the age group 13-14 years in 1987-1989. Among 111 SSPE cases only 6 children (5.4) had been vaccinated against measles while the coverage of measles vaccination in Poland reached over 95%. PMID- 2100809 TI - [Biochemical criteria of intrahepatic cholestasis in hepatitis B]. AB - Properties differentiating 13 biochemical indexes of cholestasis within a group of patients suffering from acute virus hepatitis were examined. It has proved the existence of a set of parameters of optimal properties differentiating separate states of cholestasis. This set includes concentrations of bilirubin and cholesterol esters, together with the activity of alkaline phosphatase. The variables formed a function enabling to differentiate mathematically+ the states with and without cholestasis. PMID- 2100810 TI - [Use of the "Multitest-CMI" in the evaluation of cutaneous delayed hypersensitivity reaction to antigens in patients with chronic diseases of the liver]. AB - Delayed cutaneous hypersensitivity was assessed in 120 patients (among them 109 HBsAg positive), with chronic persistent hepatitis, chronic active hepatitis, and compensated as well as decompensated liver cirrhosis by simultaneous application of seven standardized antigens and negative control ("Multitest CMI"). In 21 patients, after 12-24 months the tests were repeated. The sum of indurations of all positive responses ("score") were calculated. Responsiveness measured as results below a normal values was related to the advancing of liver disease (from 13% in chronic persistent hepatitis up to 77% in compensated and 61% in decompensated liver cirrhosis). A comparative analysis (t-Student test) of the arithmetical means of the "scores" revealed statistically significant differences between results obtained in diagnostic groups. It was also dependent from the severity of liver disease. Patients with chronic persistent hepatitis (without specific treatment) and patients with chronic active hepatitis (treated using thymus extract, TFX - "Polfa") has showed an increased "score" values. In contrast to this group, all persons with liver cirrhosis without skin responsiveness in the first and second tests (anergy) died at the period of 18 months. "Multitest CMI" can be of value in assessing of results of immunotherapy, as well as prognosis of the course of advanced liver disease. PMID- 2100811 TI - [Profile of influenza viruses in Poland 1986-1990]. AB - During the years 1986 through 1990 we isolated 69 strains of influenza viruses of which 43 were A(H3N2), 22--A(H1N1) and 4 B strains. Influenza A(H3N2) viruses isolated in 1986, 1988, 1989 and 1990 were similar to A/Mississippi 1/85, A/Inverness 3491/85, A/Sichuan 2/87 and A/OMS 5389/88. Influenza A(H1N1) viruses isolated in 1987 and 1989 were similar to A/Taiwan 1/86 and A/Singapore 6/86 strains. Influenza B viruses isolated in 1988 were similar to B/Victoria 2/87 and B/Beijing 1/87 strains. PMID- 2100812 TI - [Epidemiological situation of trichinosis in Poland 1980-1989]. AB - The epidemiological situation of trichinellosis has improved in 1985-1989 in Poland considerably. In relation to previous years (1980-1984) we could observe both decrease in a total number of cases by 691 incidence and the median of incidence rates ranged from 0.9 to 0.5 per 100,000. The number of deaths declined from 18 to 6. At the same time declined the number of provinces in which cases of trichinellosis were reported each year. PMID- 2100813 TI - [Foci of outbreaks of food poisoning and intestinal infections in Poland 1945 1989]. AB - This paper is a comparative study on epidemiological data compiled from papers of intestinal infections and intoxications in Poland during the years 45-89. The following criteria were applied: kind of food as vehicle of infection/intoxication in outbreaks; place of appearance of outbreaks; bacterial aetiological agents of cases and serotypes of Salmonella as causative agent in outbreaks. The number and percentage of outbreaks and cases in outbreaks were analyzed. Most cases and outbreaks were connected with dishes from meat in 1945 1979 and with dishes from uncooked eggs in 1985-1989. Most outbreaks during all analyzed years were connected with private homes, but most cases--with public cafeterias until 1979; with coffee, ice cream and confectionery places in 1985 1987 and with private homes in 1988-1989. Most cases and outbreaks were caused by Staphylococcus aureus in 1961-1970, Salmonella typhimurium was dominating aetiological agent in 70 ths and S.enteritidis in 83-89 years. PMID- 2100814 TI - [Toxoplasmosis reservoirs]. AB - Role and significance of some animals in the spreading and persisting of toxoplasmosis in the biocenosis were discussed. The most important sources and ways of infection in man and prophylactic measures were also presented. PMID- 2100815 TI - [Incidence of Toxoplasma gondii infections among children in the Kielce province]. AB - Toxoplasma antibodies were investigated among 639 children inhabiting the province of Kielce. The percentage of seropositive children appeared high in newborns (58.4), then dropped to 1.48 in one-year-old infants and increased to 17.4 among 6-7 year old children. The percentage was significantly higher among country children. PMID- 2100816 TI - [Analysis of anti-Borrelia burgdorferi antibodies of the IgG/IgM classes by the ELISA method. I. Evaluation of the test and the methodological principles]. PMID- 2100817 TI - [Heat stability of potency of bacterial vaccines and the titer of tetanus antitoxin of Polish production]. AB - Described the stability of potency vaccines (DTP, BCG) and immunoglobulins (human's and animal's) at storage and experimental temperatures. Thermal degradation rate and design of loss of potency in time have been determined by Arrhenius equation. Our results were similar to WHO data from preparations which have been made in another countries. PMID- 2100818 TI - [Idiotypic vaccines]. AB - The paper presents some new informations about anti-idiotypic vaccines. It discusses the advantages and disadvantages of these preparations. PMID- 2100819 TI - [Selected elements of health status of the Polish population in relation to other European countries in the light of the program "Health for all up to 2000"]. AB - Total mortality from main causes of death (diseases of circulatory system, malignant neoplasms, injuries and poisoning) life expectancy at birth, infant and maternal mortality in Poland in the years 1970-1988 were analyzed on the basis of targets of the regional strategy for "Health for all by the year 2000" (HFA 2000). It seems that it isn't possible to achieve targets concerning mortality by the year 2000. However it is possible to decrease infant and maternal mortality. Standardization of health indicators to european population allows to compare health status of the polish population to other european countries. This comparison shows that situation in Poland is not optimistic. PMID- 2100821 TI - [Tetanus patients treated at the Infectious Disease Clinic, Medical Academy, in Cracow 1980-1989]. AB - In this period 257 tetanus patients was treated. The majority of them being old age farmers. 44% patients treated in our clinic were over 71 years old. They were not actively immunized against tetanus. The principal percentage of mortality was high (42%), but it was clearly correlated with old age of patients. The co existed diseases and complications had influence to unprofitable results of treatment. Comparing 3 last tenth anniversary--general number of tetanus patients demonstrated insignificant decrease and an important increase among cases of patients more than 71 years old. Tetanus is still seriously menace to unvaccinated people in Poland. PMID- 2100820 TI - [Organization of health care for persons from the groups of high risk of HIV infection in Bydgoszcz]. AB - The existing in Bydgoszcz infectivity infrastructure was made available to AIDS infection risk groups. The AIDS infected patients make use of ambulatory and in patient health service together with other sick people. Among 72 detected infections only 2 cases remain without any connection with drug addiction. In this paper one presented advantages of the accepted organisational model as well as the effects of its functioning. PMID- 2100823 TI - Isovolemic hemodialysis combined with hemofiltration in acute renal failure. AB - One hundred cases of servere acute renal failure managed in the intensive care unit were analyzed to assess the value of isovolemic hemodialysis combined with interdialysis hemofiltration to control fluid balance. Forty-five patients were treated prior to the availability of this technique and 55 subsequently. There was a significant reduction in the oliguric period of survivors in the second group compared with the group treated by intermittent hemodialysis alone (p = 0.0459). The significant difference in age between survivors and deaths observed in the first group (p = 0.0027) was not demonstrated in the second group due to a reduction in the incidence of primarily cardiovascular deaths with an improvement in survival of the elderly. PMID- 2100822 TI - [Conservative treatment of multiple brain abscesses]. AB - Non-surgical treatment of multiple cerebral abscesses in 67 old man was described. Staphylococcus aureus was isolated from cerebral spinal fluid. The patient was treated with antibiotics and metronidazole and was discharged in satisfactory state after 40 days. PMID- 2100824 TI - Sodium thiosulfate treatment of tumoral calcinosis in patients with end-stage renal disease. AB - Three patients (2 male and 1 female) undergoing maintenance hemodialysis for more than 4 years with tumoral calcifications were treated by sodium thiosulfate. All patients had periarticular and soft tissue calcification. A considerable regression of calcified masses with concurrent clinical improvement was noted in 2 of the 3 patients. PMID- 2100825 TI - Influence of calcium antagonists on renal function and secondary hyperparathyroidism in acute renal failure in rats. AB - Glycerol-induced acute renal failure (ARF) is characterized by an increase in serum creatinine, urea, and phosphate concentration, and severe impairment of creatinine clearance. Secondary hyperparathyroidism develops rapidly during ARF. The calcium antagonist nisoldipine clearly improves renal function, which becomes evident by an improvement of creatinine clearance and attenuation of the increase of serum creatinine, urea, and phosphate concentrations. Further secondary hyperparathyroidism is ameliorated by nisoldipine treatment. In spite of normalization of the hypocalcemia in ARF by nisoldipine, weak hyperparathyroidism persists, suggesting that hypocalcemia is not exclusively responsible for elevated parathyroid hormone serum levels in ARF. PMID- 2100826 TI - Elevated plasma fibronectin levels in rats with immune and toxic glomerular diseases. AB - We measured plasma fibronectin levels by a rocket immunoelectrophoresis in rats with chronic serum sickness induced by repeated injections of ovalbumin and in rats with epithelial nephropathy induced by a single injection of adriamycin. In the early phases of the immune model, rats presented granular deposits of IgG in the mesangial area with no or descrete proteinuria (less than 40 mg/24 h). Fibronectin levels in that group were significantly higher (450 +/- 90 micrograms/mL) than in normal rats of the same age (350 +/- 46; p less than 0.01). When animals presented IgG deposits in the capillary wall, an important nephrotic syndrome developed in most of them. Fibronectin levels then increased very significantly (863 +/- 153 micrograms/mL; p less than 0.0005). In the model of adriamycin nephropathy, fibronectin significantly increased (580 +/- 110 micrograms/mL; p less than 0.0005) from the first week, when proteinuria was in a range 40-60 mg/24 h. However, the levels were higher (860 +/- 175 micrograms/mL; p less than 0.0005) when a complete nephrotic syndrome developed. At this time, plasma fibronectin levels correlated directly in both models with the degree of proteinuria and inversely with the total serum protein concentration. Our results show that plasma fibronectin levels increased very early in animals with immune and toxic damage of the kidney. The highest elevated values found thereafter, when a full nephrotic syndrome was present, suggest an increased synthetic rate of that glycoprotein linked to that situation. PMID- 2100827 TI - Sex difference in acute renal dysfunction induced by methylmercury in mice. AB - To investigate the sex-related difference of susceptibility of renal function to methylmercury (MeHg) toxicity, various doses of MeHg chloride (MMC, 20-200 mumol/kg) were orally administered to C57BL/6N mice of both sexes. On days 1, 3, 5, and 7 after MMC administration, the extent of damage to renal function and the renal Hg levels were examined. After dosing, female mice survived much longer than males. With the increase in the dose level to 200 mumol/kg, the changes of the renal Hg levels 24 h after administration showed biphasic features with a plateau of around 85 micrograms/g. The renal Hg in male mice increased more rapidly to the plateau than in females. The doses by which the renal Hg level reached the plateau were 80 and 120 mumol/kg for males and females, respectively. The time-dependent decrease of the renal Hg became much slower with dose levels exceeding 80 and 160 mumol/kg for males and females, respectively. Inhibition of phenolsulfonphthalein excretion and increase of plasma creatinine after the MMC administration were more marked in males than in females. Inorganic Hg levels in the kidney of MeHg-intoxicated mice were much lower than that of HgCl2 intoxicated mice, indicating that the involvement of inorganic Hg, a product of biotransformation of MeHg, in the renal failure caused by MMC treatment would be negligible. Although pathological changes in the renal proximal tubules of HgCl2 intoxicated mice were marked, those of the MeHg-intoxicated group were slight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100828 TI - Primary renovascular effects of erythromycin in the rat: relationship to cyclosporine nephrotoxicity. AB - Erythromycin is known to exacerbate cyclosporine nephrotoxicity. This has been attributed to the potential of erythromycin to reduce the hepatic microsomal metabolism and clearance of cyclosporine. Erythromycin may also be nephrotoxic. We tested the hypothesis that erythromycin may have direct effects on the renal vasculature which are additive or synergistic with the effects of cyclosporine. Sprague-Dawley rats were administered graded doses of either erythromycin, 2.5, 5, 7.5, and 10 mg/kg BW/min i.v. over consecutive 10-min intervals; cyclosporine, 1, 2, 3, and 4 mg/kg BW/min i.v. over consecutive 10-min intervals; or both drugs simultaneously. In separate experiments, identical doses of erythromycin or cyclosporine were infused intravenously following acute unilateral renal denervation. Infusion of erythromycin led to an initial decline in arterial blood pressure whereas infusion of cyclosporine resulted in a dose-related increase in arterial blood pressure. Despite these different systemic effects, each drug alone produced a striking decrease in renal blood flow. This effect was more pronounced when the drugs were infused concomitantly. The reduction in renal blood flow occurred in an additive manner as a direct consequence of increased renal vascular resistance. Prior renal denervation did not modify the response to either erythromycin or cyclosporine. These results demonstrate that cyclosporine induced vasoconstriction is exacerbated by erythromycin and suggest that the decline in renal function observed in patients coadministered these drugs may be due in part to additive renovascular toxicity. PMID- 2100830 TI - Current therapy in nephrology. Third international Sorrento meeting. May 27-30, 1990, Sorrento, Italy. Abstracts. PMID- 2100829 TI - The effect of protein restriction on the severity and recovery from ischemic renal failure. AB - The effects of chronic dietary protein restriction on ischemic renal failure were evaluated in rats subjected to 90 min of bilateral renal clamping. The rats were kept on either 20% casein (regular) diet or casein-free (protein-free) diet 10 days before and 21 days after renal injury. Rats on regular protein diet showed higher levels of BUN and serum creatinine and had a lower inulin clearance (microliter/min/100 g BW) than animals on protein-free diet (289 +/- 34 vs 582 +/ 103, p less than 0.05) 2 days after ischemia. However, the inulin clearance measured 21 days following ischemia was significantly higher in rats on regular diet (1468 +/- 181) than those maintained on protein-free diet after ischemia (560 +/- 167). When unilateral 90 min ischemia was performed in rats on regular diet, the postischemic kidneys showed an incomplete recovery of the inulin clearance (226 +/- 35) compared to the contralateral kidney (900 +/- 116), 21 days after ischemia; whereas in rats on a protein-free diet the inulin clearance averaged 106 +/- 17 in the postischemic kidney and 345 +/- 41 in the right kidney. When left renal ischemia and contralateral nephrectomy were performed, the inulin clearance was 1149 +/- 74 in rats on regular diet and 534 +/- 60 in rats on protein-free diet, 21 days following renal insult. These results suggest that protein restriction can play a protective role against renal ischemia in an initial phase, but it limits the late recovery from ischemia. The presence of a normal contralateral kidney inhibits the functional recovery of the postischemic kidney and a contralateral nephrectomy produces a compensatory functional hypertrophy of the postischemic kidney, even in rats on a protein-free diet. PMID- 2100831 TI - [The clinical picture and therapy of postgastrectomy syndromes]. PMID- 2100832 TI - [The current profile of pure and isolated mitral insufficiency. II. The assessment methodology. The therapeutic implications]. PMID- 2100833 TI - Ranitidine in the treatment of reflux esophagitis in patients with duodenal ulcer. PMID- 2100834 TI - [The association of ventricular pre-excitation--acute myocardial infarct. The dysrhythmic outcomes]. AB - The clinical manifestations of ventricular preexcitation, generally considered benign, may sometimes show the most unpredictable and severe evolution. Although ventricular tachyarrhythmias (those of ventricular aspect excepted) are extremely uncommon in ventricular preexcitation, cases of sudden death were nevertheless reported, their mechanism being the ventricular fibrillation. The authors have followed up the evolution of 12 patients (11 males, age between 38 and 72 years with a mean of 56 years) with acute myocardial infarction and coexistent ventricular preexcitation, previously depressed or newly detected, admitted during the last 10 years at the Coronary Unit of Iasi. It is concluded that the association ventricular preexcitation--acute myocardial infarction represents a severe risk factor by sensibly increasing the arrhythmogenic potential. PMID- 2100836 TI - [Pregnancy associated with congenital angiocardiopathies]. AB - About 2 per cent of the deliveries are recorded in patients with heart diseases. Between 1983 and 1987, 30 pregnant women with congenital cardiovascular diseases (CCVD) were studied retrospectively on the basis of clinical observation cards and operation records. Detected during the first trimester of pregnancy, 13 cases underwent therapeutical abortion, in a case in whom life was threatened a hysterotomy was performed while 16 CCVD cases carried on their pregnancies to the end. Eleven of them delivered by caesarean section and 5 had a natural delivery. In a patient with dissecting aneurysm of aorta (Marfan's syndrome) death occurred after caesarean section. Six CCVD had been corrected by previous surgery. In conclusion it is stated that in pregnant women CCVD is a high risk. Surgical correction of CCVD, preferably outside the pregnancy period, is the best prophylaxis of the incidents in the cardiac pregnant women. PMID- 2100835 TI - [Hyperthyroidism in the elderly. The clinical forms. The incidence of signs and symptoms. The evolutionary features]. AB - The last 15 years, 1939 patients suffering from different clinical forms of hyperthyroidism were hospitalised in the Clinic of Endocrinology of Iasi. The frequency of the disease increases with age, especially for the toxic nodular goitre. In older patients we have noted a non-typical clinical course of the disease, with prevailing cardiovascular signs and weight loss. The clinical course is also particular especially because of the associated pathology. We have made some theoretical considerations concerning the possible explanations of these phenomena. PMID- 2100837 TI - [Viewpoint: the ethical import in regard to psychiatric care in the modern world]. PMID- 2100838 TI - [The medical condition and the ethical implications of the care for mental patients with a long-term evolution]. PMID- 2100839 TI - [Biological markers in the accurate diagnosis of chronic alcohol intoxication- the significance of metabolic disorders (I)]. AB - Continuing the series of papers dedicated to determining some objective markers for chronic alcohol poisonings, this time we insist on the significance of metabolic disturbances in the series under study. The hepatic changes are useful in the diagnosis, in determining the consequences and in following up the therapeutical management. The study was based on the marked alterations in the lipid and protein metabolisms, these alterations being strongly connected with ethanol metabolization stages. PMID- 2100840 TI - [The risk of suicidal behavior in syndromes of reciprocal delirium interpretation induction]. PMID- 2100841 TI - [Psychoneuroimmunological connections (II)]. AB - Complementary neuro-endocrine-immune data, concomitant and successive lesions at the central nervous and immune systems as well as clinical interferences make possible the use of psychoimmunology in the various aspects of the diagnostic and therapeutic process. This paper makes references to the hypotheses regarding the share the immunobiological factors have in the pathogenesis of schizophrenic psychoses, affective disturbances, psychotic production consecutive to infections and/or febrile processes. The influence of psychic state on the evolution od some somatic affections with immunopathological determinism is also discussed. PMID- 2100842 TI - Periappendicitis among patients suspected for acute appendicitis. PMID- 2100843 TI - [The clinical, diagnostic and therapeutic characteristics in antral gastric cancer]. AB - This paper is part of a comprehensive study on subphrenic digestive cancer carried out between 1984 and 1988, representing the experience of the III-rd, I st, IV-th and emergency surgical clinics of Iasi (1530 cases). The peculiarities of gastric cancer with antral site in 231 out of a total of 612 cases, representing the experience of the III-rd Surgical Clinic, are presented. Clinically, the relative early occurrence of the symptoms, the need for an endoscopic examination and biopsy for all gastric ulcer lesions, for the antral ones particularly, are mentioned. The treatment is surgical, but it has to be associated with adjuvant therapy. For the antral site, the oncological subtotal gastrectomy was the surgery of choice (157 cases), the need of restoring the transit in a gastrojejunal manner being underlined. Total gastrectomy was performed in 12 cases. PMID- 2100844 TI - [The present-day aspects of urogenital tuberculosis. Comments on 113 cases]. AB - One hundred and thirteen new cases of urogenital tuberculosis, admitted and treated in the interval 1980-1986 (an average number of 16 cases yearly) are reported. The analysis of these patients includes age, sex, bacillary history, symptoms, clinical forms, diagnostic methods, therapeutical management and late results. Seven cases are detailed. It is concluded that the treatment with the actual tuberculostatic drugs is efficient provided the urogenital tuberculosis is early detected. In case this disease is late detected the treatment is associated, drug and surgical. PMID- 2100845 TI - [Our experience in the diagnosis and treatment of idiopathic osteonecrosis of the femur head]. AB - By analysing 32 patients with nontraumatic aseptic necrosis of femoral head, operated upon between 1 January, 1980 and 31 December, 1988, the author underlines the importance and at the same time the difficulties of an early diagnosis and the concordance which should exist between the therapeutical indications and the evolutive stage of the lesions and patients' age. PMID- 2100846 TI - [The diagnostic and therapeutic considerations in hepatic hydatid cyst]. AB - The paper is based on 213 surgical interventions for hepatic hydatid cyst. The importance of monography in the early diagnosis, detection of multiple sites and postoperative follow-up of the cases suspected of recurrence is underlined. PMID- 2100847 TI - Some risk factors for essential arterial hypertension. Comparative epidemiological investigations in industrial and school units. PMID- 2100848 TI - [The present-day epidemiological process in streptococcal infection]. AB - The changes in the epidemiological process of streptococcal infection in various periods are presented. From the great epidemics, extremely severe and with multi annual evolution reported in the past, the last decades are characterized by a permanent decrease in incidence of scarlet fever and a progressive increase of streptococcal anginas. These aspects required a more careful surveillance of the agglomeration at epidemiological risk and an estimation of the late complications frequency. The role of some factors in making scarlet fever a benign affection with a diminished epidemic character, in lowering the incidence of streptococcal infections and of their complications, among which the social-economic conditions, the standardized treatment with Penicillin G and oral penicillin, the contacts' prophylaxis with oral penicillin is underlined. In conclusion it is mentioned that, as part of primary care, the surveillance--detection, isolation, adequate treatment should be improved. PMID- 2100850 TI - [An evaluation of the results of the biochemical identification of enterobacteria]. PMID- 2100849 TI - [The determination of vitamin A in vegetable food products]. AB - Vitamin A was determined by the Sb trichloride colorimetric method in different types of margarine samples, results which observe the legislation being obtained. In order to estimate the stability of vitamin A in margarine an experiment aimed at determining the concentration in margarine samples preserved in different ways for 90 days was initiated. The obtained results point out the maintainance of vitamin A at high values, between 63 per cent and 85 per cent of the initial content, as compared to the control, in which only 50 per cent of the added quantity was found. PMID- 2100851 TI - Histological and microbiological findings of endometrium caused by the use of intrauterine device (IUD) as a method of contraception. PMID- 2100852 TI - [Biotoxicological research on a segment of the population in an industrial environment. I. Total proteins, hemoglobin, methemoglobin and cholinesterase]. AB - The inevitable chemical risks present in a synthetic threads and fibres aggregate works determine a careful and permanent surveillance of employees' state of health, especially where the occupational risk is known to exist. Besides the usual labour protection measures, screening for the early detection of some biochemical or biotoxicological changes induced by the contact with the chemical noxae in the labour environment are performed. This paper presents the results of a complex biochemical and biotoxicological screening including about 300 employees working at the polyplants in the melanin section where the major chemical noxa is acrylonitrile. The total proteins, hemoglobin, methemoglobin and cholinesterase activity were determined. PMID- 2100853 TI - [The evaluation of the teratogenesis and embryotoxicity of the pharmaceutical product Boicil tablets. I. The effect of the pharmaceutical product Boicil tablets on fertilization and implantation in rats and mice]. AB - The teratogen action of Boicil tablets was studied in two animal species, rats and mice, the prefertilization and implantation stages being the main interest. Three generations of animals were followed up. The active powder suspended in distilled water (0.1 ml/10 g for mice and 1 ml/100 g for rats) was administered per os in a single dose, prepared on spot and in two doses, 2 mg/kg body weight and 20 mg kg body weight, respectively. The administered doses were equivalent to the daily maximum therapeutic dose prescribed in humans (110 mg active principle). The first gestational day was determined differently in the two species. For estimating the effect on prefertilization, Boicil tablets was administered for 5 days before making and for its effects on the number of implantations during the first 3 gestational days. The two parameters under investigation were within normal limits and all newborn animals followed up for three generations did not present pathological microscopic and gross alterations or somatic malformations. It was concluded that Boicil tablets is not teratogenic. PMID- 2100854 TI - [The health status and bucco-dental pathology in the elderly]. AB - By analysing in 2,769 patients the relation between bucco-dental pathology and age, it was noticed that the frequency of odontic affections decreases and that of chronic marginal periodontopathies increases with age. In the elderly, a tendency towards delaying the treatment of pulp inflammations and a very high percentage of extractions performed in the chronic marginal periodontopathies (81.8%) were noticed. The bucco-dental state of health was determined in 75 old aged over 60 years, the ICORA and CPITN indices being used. Of these individuals, 93.3% presented various edentate forms, half without prosthetic appliance. Various degrees of pathological changes in the marginal periodontium were recorded in 92.3%, being more severe in women and individuals from rural areas. PMID- 2100855 TI - [Gastric niches localized in the angular notch]. AB - Gastric niches localized in angulus are rare. Their symptoms do not present essential peculiarities. Typical clinical forms of ulcer or gastric cancer with this site but also cases with atypical symptoms or even asymptomatic are reported. The detection of a gastric niche at this level and its nature, benign or malignant, are sometimes difficult by x-ray examination. The shape these niches have are described and some cases with various x-ray aspects are presented. PMID- 2100856 TI - [The production of pharmacologically active acexamic acid derivatives. I. The production of acexamic acid and its zinc salt]. AB - In view of studying the pharmacological properties of zinc acexamath a simple and cheap method for the synthesis of acexamic acid by re-evaluating some indigenous raw materials is presented. The conversion of acexamic acid into the corresponding zinc salt is highly efficient by reacting this acid with zinc oxide or zinc carbonate. PMID- 2100857 TI - New data referring to chemistry of Withania somnifera species. AB - The withanolides are a category of active principles of great pharmacodynamic importance with regard to our own research. We obtained alkaloids, 18 fatty acids, beta-sitesterol, polyphenols and phytosterols. PMID- 2100858 TI - [A study of pyramidone suppositories]. AB - Our aim was to find a formulation for pyramidon suppositories in which the physicochemical compatibility of the active substance with the excipient to be the highest. Fatty and hydrosoluble excipients were studied. Following up in time the quality of the obtained preparation, it was concluded that the fatty substances are preferable, the suppositories with glycero-gelatinous mass being more stable by an one hour freezing and two hours freeze drying. PMID- 2100859 TI - [Further comment on the importance of microscopy in clinical microbiology. The argument for the diagnosis of the skin manifestations of histoplasmosis and coccidioidomycosis]. AB - This paper presents two interesting cases: a patient with cutaneous coccidioidomycosis, the first case in Romania, and a female patient with latent histoplasmosis with cutaneous manifestations, periodically reactivated during her pregnancies. The etiological diagnosis problems of these affections in relation with the degrees of competence of the clinical laboratories is discussed. The role of direct microscopic examination in the early and more rapid diagnosis of deep mycoses is underlined. PMID- 2100860 TI - [The information problems of a prosthodontics service]. PMID- 2100861 TI - [The surgical treatment of high myopia with dura mater. The results obtained long term (a clinical study)]. AB - The paper presents the postoperative results obtained by performing scleroplasty with dura-mater in 127 progressive myopic eyes. The authors consider that the homologue dura-mater represents a high quality material to make scleral plasties. The evolution of myopia has ceased in over 60% of the cases. PMID- 2100862 TI - [The treatment of pain in cancer. The contribution of transcutaneous electric nerve stimulation]. PMID- 2100863 TI - [Current treatment in Parkinson's disease]. PMID- 2100864 TI - Iasi community alliance against AIDS. PMID- 2100865 TI - [A brain abscess of mycotic origin due to Histoplasma capsulatum]. AB - The case here presented is one of the histoplasmosis cases occurring sporadically in Romania. It is the first case with cerebral site and with the aspect of an extensive intracranial process. The diagnosis was made by a careful microscopic examination of the intraoperative specimens. PMID- 2100866 TI - [Neurosarcoidosis. Comments on 2 cases]. AB - Sarcoidosis can involve any tissue in the body and, consequently, the disease presents to clinicians of many different disciplines. We report two cases of sarcoidosis involvement of the nervous system: one male patient with right facial nerve palsy and a cutaneous involvement (supraorbital subcutaneous nodule) associated with bilateral hilar adenopathy; and a female patient presenting a hypothalamus involvement with diabetes insipidus, obesity, lethargy, sleep disturbances and amenorrhoea. In the later case an upper respiratory tract involvement was also present with nasal and tonsils sarcoidosis. A review of the clinical manifestations of neurosarcoidosis and the criteria for establishing the diagnosis is presented. PMID- 2100867 TI - [Alexandru Moruzi]. PMID- 2100868 TI - [The past activities of the Institute of Hygiene and Public Health in Iasi]. PMID- 2100869 TI - [Painters, drawers and engravers with medical themes (I)]. PMID- 2100870 TI - [Agonists and antagonists of the platelet activating factor (PAF). II]. PMID- 2100871 TI - [The 160th anniversary of the Society of Physicians and Naturalists of Iasi]. PMID- 2100872 TI - Advances in the study of proteinurias. I. The pathogenetic mechanisms. AB - The proteinurias can be due to various causes and mechanisms, with different prognosis and therapy. With respect to their mechanisms of occurrence, they are classified as: of overflow or of glomerular origin, by tubular reabsorption, by increase of tubular secretion and by protein loss from the urinary ways. These causes and mechanisms are described in detail, according to the latest data in the medical literature. PMID- 2100873 TI - Evaluation by immunofluorescence of the urinary bacteria, of the therapy effectiveness in urinary infections. AB - The therapy effectiveness in urinary infections (UI) was investigated in 27 patients by the test of immunofluorescence of the urinary bacteria (IFUB) in relationship with bacteriuria, various other biologic investigations and tests of the immune response. The study revealed a complex involvement of the immune mechanisms in the UI occurrence and persistence, as well as a parallelism between the mechanisms of cellular and humoral immunity in some of the patients. The IFUB test could reveal the eventual germ persistence at the renal parenchyma level even in the absence of significant bacteriuria, thus suggesting the necessity of a long term suppressive therapy in such cases. PMID- 2100874 TI - Applicability of the leukocyte migration inhibition test in the clinical practice. AB - The leukocyte migration inhibition test reveals in vitro the presence of lymphocyte sensitivity and, consequently, of cell-mediated immunity, to a given antigen. Applied in a variety of immune and allergic cases it proved to be useful for the positive diagnosis of the disease and/or for the detection of cell mediated immune deficiency. The results obtained recommend the leukocyte migration inhibition test in the clinical practice. PMID- 2100875 TI - Levels of SC5b--9 complement complex in plasma and synovial fluid of patients with rheumatic disease. AB - Activation of the terminal complement pathway leads to formation of the C5b--9 complex. The main effects of C5b--9 generation are tissue injury by cell lysis or by stimulation of proinflammatory mediators. In a study carried out in 42 patients, using polyclonal antibodies against C5b--9 neoantigens and C9 in an ELISA assay, we found significantly higher levels of SC5b--9 complex in plasma from the 18 patients with active systemic lupus erythematosus than those found in 10 healthy controls (p less than 0.005). In the 18 patients presenting rheumatoid arthritis and the 6 with progressive systemic sclerosis the plasma levels of SC5b -9 complex did not differ significantly from those in controls. The SC5b--9 levels found in the synovial fluid samples from the 16 rheumatoid arthritis patients were higher than the corresponding plasma ones. The ratio between synovial fluid and plasma levels was 1.2. Immunoperoxidase staining for C5b--9 was intense in three rheumatoid synovial membranes and absent in two normal synovial membranes obtained during meniscectomy. Increased levels of plasma and synovial fluid SC5b--9 reflect pathologic systemic or local activation of the complement carcase in systemic lupus erythematosus and respectively rheumatoid arthritis. Synovial membrane deposits of C5b--9 are indicative for the lytic and proinflammatory effects of complement activation. PMID- 2100876 TI - Functional and antigenic antithrombin III in angina pectoris and acute myocardial infarction patients. AB - Plasma antithrombin III was measured by an immunological approach (AT III:Ag) using an antiserum developed in our laboratory and by its ability to inhibit thrombin (functional assay) using a chromogenic synthetic substrate in 12 patients with myocardial infarction, 9 patients with angina pectoris and 10 healthy control subjects. In the early stage (3 to 24 hours after the onset of pain) of an acute myocardial infarction AT III:Ag (115.67% +/- 21.23) was found to be significantly (p less than 0.01) higher than functional (free) AT III (92% +/- 10.27). This difference was less obvious 10 days later (AT III:Ag 118% +/- 18.93; functional AT III 104.94 +/- 14.45). There was also no significant difference between AT III:Ag and functional AT III in patients with angina pectoris as well as in controls. Since AT III:Ag represents total plasma AT III while functional AT III represents only free AT III the difference between these two variables could provide informations about the amount of the anticoagulant forming complexes with activated clotting factors. It is therefore considered that the significant increase in the difference between AT III:Ag and functional AT III in the early stage of acute myocardial infarction is likely to suggest an intravascular activation of coagulation. PMID- 2100877 TI - Persistent foetal dispersion, an explanation for parasystolic arrhythmias. PMID- 2100878 TI - Decision analysis in the clinical and imaging diagnosis of acute cholecystitis. AB - The importance of clinical, laboratory and imaging data in the diagnosis of acute cholecystitis (AC) was studied in 825 patients with right upper quadrant pain hospitalized in the Surgical Clinic of the Fundeni Hospital--Bucharest, between January 1, 1986 and June 30, 1988. A number of 21 parameters were analysed in each case. Of these 825 patients, 259 were considered after surgery as AC. These 259 cases were divided, after the microscopical examination of the surgically obtained specimens, into two groups: 1) pathologically confirmed AC (137 cases) and 2) pathologically non-confirmed AC (122 cases). The importance of every parameter in establishing a histologically confirmed diagnosis of AC was determined by the diagnostic probability calculated according to Bayes'theorem. The hierarchy of the value of parameters in the diagnosis of AC was based on their capacity to distinguish between the cases histologically confirmed and those detected on surgery, but without microscopically demonstrated changes of AC. The same decision criterion was used in building the decision trees in the exploration of the cases of presumed AC. In the 825 cases with right upper quadrant pain, the main and most frequent cause was chronic calculous cholecystitis (31.8%), followed by AC pathologically confirmed (16.6%), AC non confirmed (14.7%) and chronic acalculous cholecystitis (12.4%). The most useful parameters in distinguishing between pathologically confirmed AC and pathologically non-confirmed AC were: 1) sudden onset of pain; 2) mild resistance to abdominal palpation; 3) frank peritoneal irritation; 4) stone impacted in the gallbladder neck (ultrasonography); 5) fever; 6) palpable gallbladder; 7) lithiasis (ultrasonography); 8) gallbladder wall with double outline (ultrasonography). Ultrasonography supplied a diagnostic probability of 85% for the correct diagnosis of AC in cases without a clinical picture suggestive for AC. The decision tree analysis supported the same conclusion: only ultrasonography gives a good distinction between pathologically confirmed AC and pathologically non-confirmed AC. PMID- 2100879 TI - Houses and allergic respiratory syndromes. AB - A study was carried out in 49 flats in Bucharest inhabited by 265 persons. A quantitative analysis of fungi spores was performed as well as allergologic tests with Penicillium and Aspergillus fungi (A13), Aspergillus niger (M2), Alternaria tenuis (M1), Cladosporium herbarum (M3), Dermatophagoides pteronissinus (allergenic products supplied by the Bencard firm). The infested flats presented a high percentage of Aspergillus niger spores, particularly pathogenic. The main triggering factors for the appearance of the respiratory allergenic syndromes were found to be the conditions of humidity and the inadequate ventilation. Children are more affected by exposure to these conditions of the housing microclimate. Latent sensitization to fungi and to the Dermatophagoides pteronissinus mite in about 1/3 of the children and 1/5 of the adults represents a highly significant percentage of future candidates to bronchial asthma. A first requirement for the success of treatment in such subjects is the change of inhabiting conditions. PMID- 2100880 TI - Petiveria alleaceae L. (anamu). Study of the hypoglycemic effect. AB - The combined phytochemical and pharmaceutical study of Petiveria alleaceae L. (anamu) has shown the existence in the leaves and stems of the plant of a possible hypoglycemic active principle. Extracts from leaves and stem powder were found to produce a decrease of blood sugar concentration of more than 60% one hour after oral administration in male Balb/C mice weighing 20 g fasted for 48 hours. PMID- 2100881 TI - The resistance of falciparum malaria in Africa to 4-aminoquinolines and antifolates. AB - Falciparum malaria cannot be eradicated from sub-Saharan Africa with present technology. The mainstay of malaria control in this situation is treatment of fever cases with chloroquine, aiming principally at reduction of mortality. The efficacy of this policy is now endangered because of the appearance and spread of chloroquine-resistance on the African continent. The present review examines laboratory and field research on the resistance of African P.falciparum to chloroquine, amodiaquine, pyrimethamine, proguanil, chlorproguanil and the combination sulfadoxine-pyrimethamine. Drug-resistance in malaria may be assessed with in vivo and in vitro technology. In vivo tests are simple, but the results are difficult to compare because of the influence of immunity. In vitro tests provide a more precise epidemiological tool, but their analysis should be undertaken with consideration of their technical limitations. For parasitological, immunological and epidemiological reasons, a one-to-one correlation between in vivo and in vivo grading of resistance is usually not found. Extended in vivo tests may be at least as sensitive as in vitro tests for detecting rare resistant parasites. On the other hand, the standardized grading of higher levels of in vivo resistance is arbitrary, and it is doubtful, whether such distinction has any clinical relevance. The 4-aminoquinolines (chloroquine and amodiaquine) presumably act by interfering with vital functions in the acid vesicles of parasites. Recent experiments indicate that resistance may be related to an increased rate of efflux of chloroquine from the parasite. It is caused by mutation, and at least three genetic levels of resistance have been identified. The blood stages of resistant plasmodia seem to have a biological advantage over sensitive ones, an observation that raises some hitherto unanswered questions. In the 1970s, a low degree of resistance to chloroquine was found in African P. falciparum in several localities. Resistance to the standard dose of chloroquine of 25 mg/kg was found in 1978 in tourists, who had sojourned in Kenya and Tanzania. Since then, chloroquine-resistance has spread centrifugally with increasing rapidity from an original focus in Northern Tanzania or Southern Kenya. The rate of increase in the proportion of resistant infections has generally been more rapid in the areas, where resistance has been introduced recently than in the original epifocus. The rate of increase is also generally more rapid in urban than in rural areas, an observation that can be ascribed to differences in drug pressure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2100882 TI - [Substances capable of inducing stepping (SIS) and central motor control]. PMID- 2100883 TI - [Role of polyol-myoinositol metabolic changes in the pathogenesis of diabetic macro-angiopathy]. PMID- 2100884 TI - [Effect of hypercholesterolemia on function of platelets]. PMID- 2100885 TI - [Transforming growth factor (TGF)-beta]. PMID- 2100886 TI - [Morphinan alkaloids present in mammal]. PMID- 2100887 TI - [Selenoproteins]. PMID- 2100888 TI - [Essential trace element--chromium]. PMID- 2100889 TI - [Superconducting biomagnetometer and biomagnetism study]. PMID- 2100890 TI - [Transformation of human nasopharyngeal epithelial cells in vitro]. PMID- 2100891 TI - [Bed nucleus of the stria terminalis]. PMID- 2100892 TI - [Triggered arrhythmias using the monophasic action potential technique]. PMID- 2100893 TI - [Conceptus interferon]. PMID- 2100894 TI - Lipid a component of Salmonella typhimurium carrying the derepressed Col Ib plasmids. AB - The structure of the lipid A from S. typhimurium harboring the derepressed plasmids Col Ib is very similar: i, 1,4'-bis-phosphorylated-beta-1',6-linked glucosamine disaccharide forms a backbone of the lipid; ii, lipid preparations contain four residues of 3-hydroxytetradecanoic acid at positions C3, C3' and the amide linked at C2, C2' and two free hydroxyl groups at positions C4 and C6'. Differences concern: i, substitution of phosphoryl groups by 4-amino-4-deoxy-L arabinopyranose and phosphorylethanolamine in S. typhimurium with Col Ib plasmids; ii, the degree of acylation of hydroxyl groups of 3 hydroxytetradecanoic acid by myristic, lauric and palmatic acids; iii, presence of tridecanoic acid bound to hydroxyl of 3-hydroxy-tetradecanate residue in S. typhimurium with Col Ibdrd2 plasmid. Lipopolysaccharides from the plasmid mutant strains express several times higher lethal toxicity in chick embryos compared to lipopolysaccharides from the strain with the wild type Col Ib. PMID- 2100895 TI - Fluorescence investigations on the interaction of rabbit liver D-fructose-1,6 bisphosphate 1-phosphohydrolase with bovine serum albumin. AB - The interaction of D-fructose-1,6-bisphosphate 1-phosphohydrolase (Fru-P2-ase, EC 3.1.3.11), with bovine serum albumin (BSA) results in the fluorescence quenching of BSA. BSA increases fluorescence anisotropy of Fru-P2-ase modified with o phthaldialdehyde. A program in Fortran, to simulate the experimental titration curves of BSA with Fru-P2-ase and o-phthaldialdehyde modified Fru-P2-ase with BSA, was written. For fluorescence quenching experiments the best fit was obtained for a model where one subunit of native Fru-P2-ase binds up two molecules of BSA. The determined dissociation constants at 5, 15, 25 and 35 degrees C were 2.2, 1.6, 0.83 and 0.03 microM, respectively. PMID- 2100896 TI - Alkaline phosphatase from adult rat femur. AB - Four alkaline phosphatase forms from adult rat femur were distinguished on polyacrylamide gel electrophoresis: two soluble forms of Mr 165,000 and 110,000 in the water extract, and three membrane-bound forms of Mr 130,000, 110,000 and 100,000 extractable with deoxycholate. Alkaline phosphatase after SDS-treatment disintegrated into three kinds of monomers: of Mr 80,000, 65,000 and 50,000. The soluble fraction (extract I) contained subunits of Mr 80,000 and 55,000--whereas the pellet fraction (extract II), subunits of Mr 65,000 and 50,000. Since for native forms only three types of subunits were found it seems that, apart from homodimers, there are also some heterodimers composed of the Mr 65,000 and 50,000 subunits forming the native enzyme of Mr 110,000-115,000. Two denatured monomers: of Mr 80,000 and 50,000 may form two native homodimeric forms of Mr 165,000 and 100,000 while in the pellet two monomers: of Mr 65,000 and 50,000 may correspond to three native alkaline phosphatase forms: of Mr 130,000, 110,000-115,000 and 100,000. Probably the Mr 110,000-115,000 form is a heterodimer composed of subunits of Mr 65,000 and 50,000. PMID- 2100897 TI - Changes of femoral alkaline phosphatase activity in adult rats treated by sorbitol enriched or vitamin D3 deficient diet. AB - The effect of vitamin D3-deficiency and dietary sorbitol on serum calcium level, the activity and alkaline phosphatase (AP) pattern in femoral epiphysis were studied. Rats fed a diet supplemented with sorbitol or vitamin D3 showed the same serum calcium concentration and AP activity in serum and femur. Rats fed a vitamin D3-deficient diet displayed decreased serum calcium concentration and increased AP activity both in serum and femur. Four forms of AP were isolated from the femur of these rat groups: of Mr 100,000, 110,000, 130,000 and 165,000. Rats receiving the diet supplemented with sorbitol showed a marked rise in the activity of the Mr 165,000 form, and appearance of a new monomer of 100,000, never formed in two remaining groups. PMID- 2100898 TI - The substrate specificity of glycerol ester hydrolase from pig aorta and serum. AB - The activity of glycerol ester hydrolase (GEH) from aorta wall, at optimum pH and triacylglycerol substrate concentration (optimal for each substrate) decreased in the following order: C18:1 greater than or equal to C18:2 greater than or equal to C18:0 greater than or equal to C18:3 greater than or equal to C16:0. At optimum pH and the same substrate concentration (1 mM), the activity of GEH from aorta wall decreased in a slightly different order: C18:1 greater than or equal to C18:2 greater than or equal to C18:3 greater than C18:0 greater than C16:0 and that of the enzyme from serum in the order: C18:1 = C18:3 greater than C18:2 greater than or equal to C16:0 greater than or equal to C18:0. These differences in substrate affinity of GEH may influence the metabolism and accumulation of acylalcohols and alcohols in arterial wall and serum. PMID- 2100899 TI - Monoclonal antibodies in the treatment of endotoxin shock (a review). PMID- 2100900 TI - Modulating the microbial colonization of the gastrointestinal tract by oral administration of defined Escherichia coli strains. III. Lipopolysaccharide specific IgA in the intestine after oral administration of Escherichia coli. AB - The assumption that local immunologic mechanisms are responsible for findings on the specific microbial colonization of the gastrointestinal tract of mice, is confirmed by results described in the present communication. Quantitative examination of intestinal lavage fluids after oral administration of germs by ELISA showed that (i) there is a critical dose above which a significant increase of IgA synthesis is observable; (ii) low antibody levels could be detected already in the untreated control group. It may be assumed that--regardless of the biological characteristics of the administered strain, namely, substrate and receptor competition--the stimulability of local immunity provides against permanent monocolonization with displacement of the autochthonous Enterobacteriaceae in adult and immunocompetent hosts. PMID- 2100901 TI - Bacterial translocation after cold stress in young and old mice. AB - Spontaneous translocation of the normal intestinal flora was observed in higher rate in old mice being in a state of thymus involution than in young ones. The proportion of bacterial translocation 24 and 48 h after cold stress increased in both young and old mice, the increase of translocation as compared to controls was larger in case of young mice than in old ones. The distribution of isolated bacterial strains according to Gram stain also differed in young and old groups. PMID- 2100902 TI - Effect of mannozym treatment on plasma fibronectin concentration in germfree and conventional mice. AB - As a result of a single intraperitoneal treatment with 1 mg/ml of Mannozym (M) the plasma fibronectin (FN) level was significantly increased both in germfree (Gf) and conventional (Cv) mice, and though it started from a lower value in Gf mice, it rose to a similar level to that of Cv animals. The maximum of FN level was observed on the first day after treatment both in Gf and Cv mice. It had returned to normal by the 7th day in Cv mice, but it was higher in Gf mice as compared to untreated controls even on the 14th day. Thus the increase of FN level was of higher degree and longer duration following M treatment in Gf mice than in Cv animals. In treated Gf mice the plasma FN concentration was in the same range as in untreated Cv mice even at the termination of experiment. Both in Gf and Cv mice, there was a relative spleen weight increase, the degree of which was similar, but the duration was longer in Gf mice than in Cv ones. PMID- 2100904 TI - Characterization of an intermediate adenovirus strain. AB - An intermediate strain of human adenovirus of subgenus D was investigated by type specific serological reactions and restriction endonuclease analysis. The latter method showed the strain identical to the prototype strain of human adenovirus type 9 as well as did serum neutralization tests. In contrast with the previous methods haemagglutination inhibition tests showed the strain related to both the prototypes strains of human adenovirus 9 and 13. PMID- 2100903 TI - Separation and some properties of an endo-1,4-beta-D-xylanase from Aspergillus flavipes. AB - A fungal strain isolated from stored wheat straw and identified as Aspergillus flavipes was found to produce an extracellular endo-1,4,beta-D-xylanase when grown in shake-culture of a mineral salt medium containing 0.1% wheat strawxylan as a sole source of carbon for 3 days at 28 degrees C. The enzyme was separated by precipitation with ammonium sulphate and desalted by Sephadex G-25 column. Fractionation and purification of the enzyme were carried out by chromatography on Bio-Gel P-100. The purified enzyme (mol wt 45,000) was found to release xylooligomers only from beta-1,4-xylan. It showed maximum activity at pH 5.0 and temperature 55 degrees C. PMID- 2100905 TI - Genetic disease and childhood mortality. PMID- 2100906 TI - [Genetic counseling in relation to drug intake in early pregnancy]. AB - In a series of 153 women with intake of drugs during early pregnancy the pregnancy was terminated in 22% of all cases. There were the following results of the 119 non-terminated pregnancies: delivery of a normal, healthy baby: 84%; abortion: 5%; still birth and premature birth, respectively: 3,5%. An abnormal phenotype was seen in 7% of the newborns, but only 3 cases with major malformation (cleft lip, club-foot, cataract) could be noted. Compared with normal pregnancies the results do not confirm an enhanced risk for malformations by intake of drugs during early pregnancy. Unfounded anxiety of physicians as well as of pregnant women with indicated pharmacotherapy should be reduced by better information and education. PMID- 2100907 TI - [Growth in head circumference: parent-child correlation and secular trend]. AB - Head circumference is an important growth parameter; it is closely related to brain development in normal infants. Therefore regular meticulous measurements of head circumference can give diagnostic hints of abnormal brain growth, i. e., reduced growth as in severe malnutrition or accelerated as in hydrocephalus, for example. The results presented here are based on the Bonn Longitudinal Study on growth and development; 150 infants (65 preterm and 85 full-term) were measured regularly from birth. Head circumference of the parents was also measured. For the full term infants the highest correlation was found between mother and daughter (r = 0.75), in the preterm infants the highest correlation was seen between mother and son (r = 0.65). In the Bonn Longitudinal Study and in a recent additional Bonn Study no positive secular trend of head circumference was observed which agrees with results of others. Interestingly enough, growth of head circumference behaves completely differently from that of height in the Bonn Study, where a positive secular trend was observed. PMID- 2100908 TI - [Clinical and anthropologic aspects of form and size of the child's head]. AB - The author recommends the classic direct cephalometry for measurements in clinical anthropology during childhood. It is referred a trend of debrachycephalization in the Czech child population. The presented results prove a decreasing cephalic index from birth up to 3 years of life and a relationship between positioning of the child and the shape and size of the child's neurocranium. PMID- 2100909 TI - The secular trend in The Netherlands. The third nation-wide growth study. PMID- 2100910 TI - [Analysis of the correlation of 18 physical measurements in 3-month-old children]. AB - In 1985 and 1986 anthropologic measurements at 18 measurements points were conducted on 1,584 children at the age of 3 months. We evaluated these measurements by means of correlation-, factor- and principal characteristic analysis. Three groups of correlating measurements were found: length, skeleton robustness and body mass. The following measurements are recommended as most important for physical investigations of babies: for length: height and arm length; for skeleton robustness: shoulder width; for body mass: weight and subscapular skinfold thickness. PMID- 2100911 TI - [Relations between postnatal weight loss and feeding of newborn infants with breast milk]. AB - Data presented in this study prove that in term neonates as well as in premature newborns the normal postnatal fall of the body weight is of a smaller extend when breast milk, especially breast milk from their own mothers, is used for nutrition. PMID- 2100912 TI - A longitudinal study of the growth of infants with low birth weight: growth and development of infants appropriate for gestational age and of infants small for gestational age. PMID- 2100913 TI - [Correlation between somatic developmental status of newborn infants and some sociodemographic data]. AB - Data obtained from 10,108 newborns of parents of gypsy native language delivered during 1973-1983 were compared to national population's data of 1978. When comparing the data of gypsy group which is living under very disadvantageous social, cultural and health conditions to the appropriate national data the following differences have been found. The physical development of gypsy infants included in this study is much more worse than that of the national average. For the poorer physical development of gypsy children the disadvantageous social and hygienic conditions together with low educational attainment is responsible rather than the different genetic background. This conclusion is proved by findings of the study that the trend of national data according to the educational attainment is very similar to that of the appropriate data of gypsy group. PMID- 2100914 TI - [Constitution and acceleration from the allometric viewpoint exemplified by data from a longitudinal study in Braunschweig]. AB - Anthropometric measurements of constitution and acceleration are only comparable if they are allometrically standardized. Individual results are only applicable to the population from which they come. Further connections are explained on the basis of date from a longitudinal study. PMID- 2100915 TI - [Secular trend of physical development and its significance for pediatric practice]. AB - A review is given on the secular trend of the somatic development, on its part phenomena and on the mutual interest of the human biology as well as the pediatric practice. The author presents two example of a positive secular trend in Hungary concerning the growth of height and the maturation in girls, respectively. This last one, however, shows also a negative tendency in the last decades. PMID- 2100916 TI - [Physical dimensions and skinfold thickness in childhood]. AB - Five measurements of body circumferences were related to the results of determinations of the subcutaneous fat thickness using caliper measurements. The analysis of data obtained from 10,661 infants and children aged between 1.5 to 15 years do not show constant correlations of the parameters measured during the periods of childhood. PMID- 2100917 TI - [Anthropogenetics and suitability for sports of children and adolescents]. AB - Methods, tests and criterions for selection of children and adolescents talented for sport are described. A review is given on the author's investigations on the genetic conditionality of the prerequisites for performances in sport based on twin studies and on the developmental stability of the selection criterions tested. PMID- 2100918 TI - [Growth parameters of female athletes during periods of high training load]. AB - Studies of children participating in elite sport training programmes revealed growth disorders. Longitudinal analyses of female gymnasts (whose bone age was distinctly below chronological age) over a period of two years do not suggest a general tendency to growth inhibition. However, the marked variation in the longitudinal data may indicate retardation in individual cases. An evaluation of the growth parameters is of practical importance for the medical care of children participating in intensive training programmes. PMID- 2100919 TI - [Effect of bronchial asthma on growth and physical development]. AB - Radiologic bone measurements for determination of the skeletal maturation were conducted in 243 children with bronchial asthma. The authors describe marked retardation of skeletal maturation as a general phenomenon of the atopic asthma. The grade of retardation is greater in atopics than in non-atopic asthmatics. The grade of quantitative response to allergic tests is significantly correlated with the extent of retardation of the skeletal maturation. It is discussed that in addition to asthma, eczema and allergic rhinitis the retardation of the skeletal bone maturation could be a further original manifestation of atopia. PMID- 2100920 TI - [Metric index and blood pressure values in 15-year-old students]. AB - This longitudinal study of blood pressure in adolescents contains the mean and regression of systolic and diastolic blood pressure according to the metric index as the body mass index. The results show higher levels of blood pressure in pyknopyknomorphs than in mesomorphs and lepto-leptomorphs. PMID- 2100921 TI - [Anthropology and electrocardiography]. AB - Compared with the conventional ECG lead systems, the corrected orthogonal leads by Frank and the leads by Nelson constitute progress, especially if one considers their mathematical and physical comparability and the possibility of recording vectorcardiograms projected on to three orthogonal levels. The discussion about these lead systems and their application in infancy and childhood cannot be considered concluded; above all questions of their information content must be definitively clarified. PMID- 2100922 TI - [Secular acceleration and the electrocardiography in childhood and adolescence]. AB - As a consequence of advanced growth episondes and an increase in the final height of adolescents, resulting in changes in the cardiovascular system, an "acceleration" of electrocardiographic parameters and special morphological features of the ECG can be observed. The trend towards a closer relation between ECG parameters and body height than age, as seen in our probands as well as in the literature, reflects the influence of acceleration on the electrocardiogram. PMID- 2100923 TI - [Problems in the collection and evaluation of menarche data, exemplified by empirical data from two Bremerhaven child development studies]. AB - Two Bremerhaven growth studies serve as examples for analysing methods of collecting and evaluating data on menarche age. Problems are outlined which arise when inadequate methods are used. PMID- 2100924 TI - [Continuous menarche observations in a closed population]. PMID- 2100925 TI - [A method for predicting the onset of menarche]. AB - For the period of 1981-1984 the author collected data on the menarche age of more than 32 thousand girls aged between 10-18.5 years by the so-called status-quo method. The evaluation was carried out by means of 19 factors. A model was developed on purpose to prognosticate the age of menarche. PMID- 2100926 TI - [Range of variation of sex maturation markers]. AB - Nation-wide investigations on the sexual maturation (secondary sex characteristics) have been carried out for the first time in the GDR in 1984 and 1985. They were part of a research project of the Ministry of Health concerning health during childhood and adolescence. The study was organised and coordinated by our Institute of Anthropology in Berlin. More than 17,000 children and young persons of ages between 8 and 16 years have been recorded. The data have been analysed. The analysis was performed after the colour tables of van Wieringen and coworkers as well as using additional adapted tables. Most important results concerning the indicators of sexual maturation are being presented here. PMID- 2100927 TI - [Development of sex characteristics in relation to nutritional status]. AB - Results of anthropometric measurements and determination of the state of sexual maturation in 8703 girls and 8685 boys aged between 8-16 years show that, if these results are related to the nutritional state, the development of the signs of sexual maturity is dependently on the nutritional state. PMID- 2100928 TI - [Human ontogenesis from a behavioral biological viewpoint]. AB - General aspects of the human ontogenesis are analyzed theoretically from the view point of behavioural biology. The functional integration of the three levels of individual development--actual genesis, ontogenesis, phylogenesis--leads the author to the term "hologenesis". Based on the concept of hologenesis developmental problems are discussed in terms of behavioural biology. In this context behaviour is defined as the organismic interaction with the environment on the basis on information of the hologenetic process. Behavioural data on fetal, neonatal, and postnatal life are discussed in relation to interaction with the peristatic milieu. PMID- 2100929 TI - [Results of long-term longitudinal studies of lateralization of motor and sensory functions]. AB - Results of a follow-up study of the lateralisation of motory and sensory functions are presented. The development of handedness, the preference of one leg, one eye and one ear was determined for about 200 probands at the age of 3/4 to 17 years. Three types of lateralisation were found: (i) the "non-right" motory and sensory functions type (ambivalence); (ii) the "right" motory functions/"non right" sensory functions type; (iii) the "right" motory and sensory functions type (univalence). PMID- 2100930 TI - [Improving mathematical performance of students by training in mental processing time]. AB - Psycho-physical presuppositions may be influenced by well planned training. With regard to their individual presuppositions test persons with very low mathematical performances show the best growth of performance after training of mental speed. PMID- 2100931 TI - [Secular trend of body height and "acceleration" or fluctuation in growth in height in child development--on questions of methodology in relation to pre historical skeletal remains]. AB - The possibility of obtaining information on growth and development from prehistoric and early historic skeletal remains of children and juveniles is discussed. Beside simple measurements of length there are some new methods of assessment, e.g. control of "Harris' lines", thickness of bone corticalis including cremated bones, diameters of neural canal and vertebral body height. Estimation of age based on dentition must be presumed in every case. Results show oscillations rather than a linear or curved trend in only on direction. The phenomenon of acceleration can also not be seen as a return to earlier phases of mankind. PMID- 2100932 TI - [Physical measurements of healthy, athletic girls 9-12 years of age in percentile values]. AB - Eight anthropometric data from 550 healthy sporting girls aged 9-12 years are presented as percentiles in tabular form. The results are of importance for the medical practice. PMID- 2100933 TI - Intestinal lymph of ruminants. I. Operative techniques for collecting intestinal lymph from ruminants. AB - Operative technique developed for collecting intestinal lymph from cattle and sheep are described. The method of creating an external anastomosis between intestinal lymph and the posterior caval vein (lymph-caval anastomosis), the postoperative care of animals, and the blood sampling technique are presented in detail. The optimal period of use of the anastomosis is 15 to 18 days. Its further use is of no reason, since the intestinal lymph changes in quality. PMID- 2100934 TI - Changes in the electric resistance of the vaginal mucus in oestrous sows. AB - Changes in the electric resistance of the vaginal mucus were monitored in a large pig herd at 4-h intervals with a heat detector (Hauptner, Federal Republic of Germany) in multiparous sows (n = 16; litter size = 11.4 +/- 2.9) that showed a positive standing test and conceived. The initial value of resistance was 74.4 +/ 7.4 ohms. In 36 h this value gradually increased to 93.6 +/- 7.6 ohms. One to 2 h after the artificial inseminations (AI) lower resistance values were obtained, though the difference was not statistically significant. In the second part of the experiment 73.9% and 82.7% of the gilts (n = 92) and multiparous sows (n = 98) conceived, respectively, with an average litter size of 9.6 +/- 2.2 and 11.0 +/- 2.7, respectively. The conception rate of animals that immediately before AI had vaginal mucus resistance values between 75 and 90 ohms was about 20% higher. The only exception were 8 multiparous sows which had an average vaginal mucus resistance of 70 +/- 4.6 ohms after the first insemination. Litter size was also the biggest in sows with vaginal mucus resistance between 75 and 90 ohms. This difference was statistically significant for the multiparous sows. The heat detector is considered to be a useful complement to conventional methods of oestrus detection. PMID- 2100935 TI - Epidemiology of Salmonella derby strains isolated from swine, pork and pork products. AB - A total of 35 Salmonella derby strains, isolated from 6 types of samples of porcine origin from 9 different places in Hungary were examined for their characteristics. Thirty-two strains (91%) were of phage type 25, 2 (6%) of phage type 15 and 1 (3%) of phage type 58. Colicin production was observed in 3 (9%) strains. Five strains (14%) were found to be resistant to tetracycline (Tc). The strains harboured plasmids of 2.2, 2.4, 3.4, 4.2 and 72 Md. The 72 Md plasmid appears to be characteristic of S. derby and possibly encodes Tc resistance. The 72 Md plasmid belonged partly to incompatibility (Inc) group I1, while the other plasmid of the same size belonged to Inc. group B. The findings suggest that healthy salmonella carrier pigs carried the infection from the farm to the abattoir. Slaughtering of infected pigs may have led to contamination of the carcasses and, thereafter, that of the pork and pork products. PMID- 2100936 TI - Feeding trial in pigs with a diet containing sodium n-butyrate. AB - Pigs weighing 7 to 102 kg were fed a diet containing 0.17% sodium n-butyrate. The diet increased the average daily body mass gain of pigs by 23.5%. Due to its dietetic effect, feed consumption increased by 8.9%. However, owing to the higher feed conversion, specific feed utilization was reduced by 11.8%. The experimental diet markedly reduced the percentile proportion of coliform bacteria in the ileum as compared to Lactobacillus ssp.: it decreased the coliform count and increased the counts of Lactobacillus spp. The diet increased the length of ileal microvilli and the depth of caecal crypts. It raised the concentration of immunoreactive insulin in the blood plasma. The feed supplemented with sodium butyrate did not alter adversely the clinical indices tested. It reduced feed costs by 9% and increased the returns from sales by 13%. As the additive is normally produced by microbial fermentation in the large intestine, it is not alien to the body. Sodium butyrate exerted its favourable effect in 3.6- to 24.2 fold lower concentrations than the organic acids (citric acid, fumaric acid, propionic acid) used earlier. With respect to its favourable biological and economic effect, sodium n-butyrate can be recommended for use in pig feeding as a growth promoter. PMID- 2100937 TI - Diagnostic value of intravenously administered johnin purified protein derivative (PPD) in bovine paratuberculosis. AB - The diagnostic value of intravenously administered johnin purified protein derivative (PPD) was studied in 45 cattle of different age, coming from herds infected by, or free from, Mycobacterium paratuberculosis. In addition to observing the clinical symptoms, the animals' sera were assayed for specific antibodies by the complement fixation (CFT) and immunodiffusion (AGID) tests. The blastogenic transformation of peripheral lymphocytes was determined on the basis of 3HTdR incorporation. Changes in the neutrophilic leucocyte/lymphocyte ratio of the blood were also monitored. Detection of the pathogen in the faeces was attempted by microscopic examination and by culturing. Combined evaluation of responses elicited by intravenously administered johnin PPD can be a valuable aid in recognizing infected animals, particularly those among the heifer progeny of infected cows. PMID- 2100938 TI - Evaluation of cell-mediated immunity during chronic organophosphate pesticide intoxication in mice and goats. AB - The status of cell-mediated immunity (CMI) after pesticide exposure was assessed in mice with the help of skin sensitivity and graft versus host reaction tests. It was observed that at 24 hours post-challenge CMI values did not differ significantly from the control, indicating no effect of quinalphos treatment in mice. Goats receiving monocrotophos at a dose rate of 1.0 mg kg-1 body mass for 40 days gave a similar result when CMI was tested with the help of the chemical sensitizer dinitrofluorobenzene (DNFB). Thus the results clearly indicate that the tested organophosphates do not interfere with cellular immunity in the intoxicated animals. PMID- 2100939 TI - Mycotoxin research in the Hungarian Central Veterinary Institute. AB - Mycotoxin research conducted in the Hungarian Central Veterinary Institute is reviewed briefly. The effect of zearalenone was studied by experiments in several animal species (cattle, pig, sheep, chicken, goose, duck, guinea fowl, fish) and in cell cultures in vitro. The chicken (Gallus domesticus) has proved to be resistant to the toxin. In the susceptible species zearalenone causes the most severe damage to the sexual organs. The metabolism of zearalenone, T-2 toxin and diacetoxyscirpenol was also studied. These toxins are resistant to physicochemical factors but are easily transformed in biologically active environment. The acute toxicity study of trichothecene toxins is described along with morphological changes, with particular respect to those of the lymphoid and myeloid organs. Trichothecene toxins impair the natural defence mechanism of the organism and result in the manifestation of different diseases (swine dysentery, caecal coccidiosis). Deoxynivalenol contamination of the feeds, first of all of wheat, is common in Hungary. Its effect on pig fattening was investigated in a field trial. The toxins of different storehouse moulds were also examined. PMID- 2100940 TI - Electron microscopic study of the peritoneal macrophages of rats with chronic fascioliasis and the carcinogenic effect of diethylnitrosamine. AB - The ultrastructure of peritoneal macrophages of rats with chronic fascioliasis and the carcinogenic effect of diethylnitrosamine (DENA) were studied. The phagocytic activity of macrophages on Staphylococcus aureus were examined in its dynamics (in the 1st, 5th and 24th h). The ultrastructural changes of the macrophages were the most pronounced in animals injected eight times with DENA and the weakest in the group of animals infected twice with Fasciola hepatica. As to the phagocytic activity of the macrophages the following events were observed: attraction and adhesion of the bacterial cells to the surface of the macrophages, their inclusion in phagosomes; partial to full lysis of the bacteria; and formation of residual bodies. The phagocytosis was the most active in macrophages obtained from animals infected twice with Fasciola hepatica and the weakest in those from the DENA-treated animals. PMID- 2100941 TI - New aspects of thyroid physiology: a review. PMID- 2100942 TI - Correlation between thyroid hormone level and blood pH in cows and in their offspring. AB - Thyroid hormone levels in the plasma and blood pH were compared in 38 newborn calves and their dams immediately at parturition, then 24 and 72 h thereafter. Both thyroid hormone levels and pH exhibit much higher variation in calves than in cows. Applying a linear model at different sampling times, a weak (r = -0.112 to -0.397) but significant (P less than 0.05) negative correlation was found between thyroid hormone levels and blood pH in calves 24 and 72 h postpartum. At birth, when no correlation was found with linear approach, a polynomial regression model showed curvilinear relationship between thyroid hormone levels and blood pH in calves. Since these correlations could not be substantiated by comparing data of different sampling times, one can conclude that the possible relationship of thyroid hormone levels and blood pH is a complex one. Revealing the underlying mechanism of the above observations requires further study. PMID- 2100943 TI - The effect of tannin treatment and subsequent urea supplementation of sunflower meal on the in vitro digestibility of its crude protein for ruminants. AB - The effect of tannin treatment (TSFM) and subsequent urea supplementation (TSFM + U) on the digestibility of sunflower meal (SFM) protein was studied by means of a three-phase laboratory method simulating the ruminant's digestion. Under the influence of the ruminal fluid 67% of SFM protein, 62% of TSFM protein and 58% of TSFM + U protein was degraded. The pepsin and pancreatin digestibilities of rumen undegraded protein (UDP) were as follow: 58.2% (SFM), 56.6% (TSFM), 43.3% (TSFM + U), and 22.0% (SFM), 28.8% (TSFM), 17.5% (TSFM + U), respectively. The four fractions (dissolved protein, oligopeptides, amino acids, and ammonia) of rumen degradable protein (DP) were also determined: 85 to 92% of rumen degradable protein was recovered in these four fractions. Owing to tannic acid treatment the quantity of dissolved protein decreased and that of oligopeptides increased. PMID- 2100944 TI - [The breasts--a topic of gynecology]. PMID- 2100945 TI - [Obstetrical problems in family planning]. AB - The author describes medico-social aspects of the family planning, reproductive health of the woman and some problems of the perinatal period of the newborn. Rational planning of the family leads to favourable conditions and possibilities for protection of the health of the pregnant woman, mother and children, for diminution of abortions, for extending natural feeding of the suckling baby. Effects of some factors in active and right family planning and their impact on the health of the woman and on the level of the basic obstetric parameters: maternal mortality, perinatal mortality, sterility, etc. are analysed. PMID- 2100946 TI - [Antibiotic prevention and treatment in cesarean section]. AB - The aim of the authors ia to study the role of antibiotic prophylaxis in cesarean section for prevention of infectious complications during puerperium. 443 deliveries were studied, which took place by cesarean section at the obstetric clinic of the Higher Medical Institute in the town of Pleven for a 2-year period. One antibiotic was administered in 96 women (21.67%) up to the third day, but in 62 women--up to the sixth day (14.00%). Two antibiotics were used is 49 parturients (11.06%) up to the third day, but in 131 women (29.57%) up to the sixth day. The combination of 3 antibiotics, containing a preparation against anaerobic infection, was used in 43 women (9.7%). The most frequent complication- endometritis was observed in 17 of operated women (3.84%), but suppuration of the operative wound--in 8 women (1.81%). After a 6-day prophylaxis with penicillin and gentamycin the frequency of endometritis was higher than that with ampicillin and gentamycin (11.76% against 2.60%). An impression was created that there was not a single case with endometritis and only one case with suppuration among 62 (13.99%) women operated without usage of antibiotics as well as in 145 (32.73%) women with antibiotic therapy up to the third day. All these parturients were with low risk of puerperal infection. Our position is that they do not need antibiotic prophylaxis. PMID- 2100947 TI - [The diagnosis and treatment of lung barotrauma in newborn infants at risk]. AB - Lung barotrauma (LBT) are some of the most frequent complications in the course of mechanical ventilation (MV) in risk newborn infants. The interstitial emphysema among them is the most frequent cause for development of chronic hung diseases, but the pneumothorax induces shock state, connected with high mortality. A retrospective analysis of the histories of the disease was carried out on 18 risk newborn infants with clinical and roentgenological data for pneumothorax. Blood gases and acid-base balance were examined before the incident as well as at definite intervals after drainage of extra-alveolar air. There were considerable deviations. The results indicate considerably better prognosis of the disease, when the drainage is put immediately after establishment of the clinical diagnosis. Mortality is high, when the drainage of pneumothorax is put after the first hour. PMID- 2100948 TI - [Our experience with the treatment of Chlamydia trachomatis in acute and chronic inflammatory diseases of the female genitalia]. AB - The effect of antibiotic treatment was studied on 41 women with inflammatory gynecological diseases at the acute and chronic stages as the patients were examined for presence of Chlamydia trachomatis in the endocervix. The high frequency of isolated Chlamydia trachomatis in these women (44.1%) with predominance at the age of 21-25 years show the important role of Chlamydia trachomatis in the etiology of the inflammatory process. Possibilities for therapeutic effect by using various antibiotic combinations are discussed. PMID- 2100949 TI - [Malignant melanoma of the vulva and vagina (a report of 4 cases and review of the literature)]. AB - Three women with malignant melanocarcinoma of the vulva and one woman with malignant melanocarcinoma of the vagina were treated at the gynecological clinic of the National Oncological Center for the period of 1983-1988. The mean age of the patients was 52 years. In all patients melanocarcinoma was IV-V degree according to Crark as in 2 women it was pigmented, but in 2 women--achromatic. Radical vulvectomy was performed on patients with melanocarcinoma of the vulva as in 2 patients inguino-femoral lymph dissection according to Ducuing was made, but pelvic lymph dissection according to Taussing was performed in 1 woman as well. The operation of Werthaim-Meigs and extirpation of the vagina was performed in the woman with melanocarcinoma of the vagina. Two of the patients died after 13 and 28 months after the primary treatment due to generalization of the process, but 2 of the patients developed a relapse of the disease 10 and 14 months after treatment. Anterior and posterior exenteration of the pelvis was performed in the woman with a relapse of the vaginal melanocarcinoma. Two patients are still alive for a period of 6 and 8 months and chemotherapy continues. A literary review is presented and possibilities for more effective treatment are discussed. PMID- 2100950 TI - [Endometrial cancer. A clinico-morphological study]. AB - Knowledge of cyclic changes, connected with hormonal action and precancerous states, is of substantial significance for early diagnosis and timely treatment of endometrial carcinoma. Eighty six women with endometrial carcinoma, established histologically, were studied prospectively. A parallel study of histological differentiation of the tumour and some clinical symptoms was made. Serum level of F2 were examined as well. It was found that they were more manifested in highly differentiated adenocarcinomas. Women with histories for dysfunctional uterine bleedings suffering from hypertonic disease diabetes, obesity and with increased levels of E2 were considered as a risk group for development of endometrial carcinoma. PMID- 2100951 TI - [The psychosomatic aspects of defloration (a sociomedical study)]. AB - The phenomena surrounding the first sexual act are examined rather poorly from their psychosomatic side during investigation of human sexuality and reproductive behaviour. Frequency and character of the bleeding during defloration, experienced pain, a complex of fear due to pain and bleeding, motivation, evaluation and self-esteem of the behaviour, self-esteem on timeliness of the first sexual act, the attitude of the husband to defloration performed by other partner before marriage. Some of the obtained data are compared with similar data, obtained by analogous studies in some European countries. Inferences are made, which could be used by services, rendering consultative help to young women, candidates for marriage and their partners. PMID- 2100952 TI - [Spermatological disorders in patients with postmumps orchitis]. AB - The author studied spermatozoa parameters in 27 patients, undergone postparotitic orchitis with fertile problems. Unilateral localization of the damaged testis was established in 21 men, but bilateral localization--in 6 men. The author divided the patients into two groups--the first group included patients, who underwent orchitis before 10 years of age and the second group of patients, who underwent the complication orchiepididymitis after 10 years of age. After examination of the ejaculate he found disturbances following disturbances with unilateral localization of orchitis in the first and second group in respect to the number of spermatozoa mil/ml in the following ratio 32:12, the ration of spermatozoa motility, described in percentage, was 39:10, but the ratio of velocity mic/sec was 8:5. Spermatogram showed azoospermia with definitive sterility in both groups of patients, who had bilateral localization of postparotitic orchitis. PMID- 2100954 TI - [Problems of vaginal candidiasis. III. The trends in current antimycotic therapy]. PMID- 2100953 TI - [The plasma amino acid profile of women with a normal pregnancy and in pre eclampsia]. AB - The authors studied the level of some amino acids in the plasma of 10 women with normal pregnancy as well as of 16 women with moderate form of pre-eclampsia. 21 amino acids were determined by a liquid chromatograph, consisting of an automatic controller of the gradient, nonautomatic injector, fluorimetric detector and recording device. The results showed that there were differences in amino-amides of women with normal pregnancy and of nonpregnant women. Concentrations of a large part of amino acids were not changed, but some of them increased--aspargic acid, glutamate, threonine and phenylalanine or reduced--cytroline, methionine, ornithine, glycine, aspargine, alpha-amino acid during pregnancy. The values of amino-acids in women with normal pregnancy and in women with moderate form of preeclampsia did not differ. Ethanol-amine is the only exception and it is found in almost half of the women with preeclampsia. This is an original finding, which deserves further study. PMID- 2100955 TI - [Toxoplasma infection and pregnancy]. PMID- 2100956 TI - [Current aspects in the study of the embryology and functional morphology of the human placenta]. PMID- 2100957 TI - [Hypertension and hypotension in the newborn infant]. PMID- 2100958 TI - [The older primipara]. PMID- 2100959 TI - [A rare case of a giant myoma]. PMID- 2100960 TI - [A case of a diagnostic error in Meckel's diverticulum with a right-sided torsive ovarian tumor]. AB - The author described a case of a woman with Meckel's diverticulum, appendectomized, who was admitted to the gynecological ward after rejection of acute surgical abdomen with diagnosis ovarian tumour. Meckel's diverticulum with chronic serous-purulent peritonitis was established after laparotomy. Inferences are made in respect to this not quite rare intraoperative finding of Meckel's diverticulum and to the necessity of searching and its respective removal during laparotomy on other occasion. PMID- 2100961 TI - [Gas gangrene following criminal intervention in a woman 5 months pregnant]. PMID- 2100962 TI - [A rare case of adnexal torsion in combination with advanced and tubal pregnancies]. PMID- 2100963 TI - [A clinico-pharmacological study of the preparation farmatsinon in gynecological hemorrhages]. PMID- 2100964 TI - [Practical observations of the use of the contraceptive preparation Anteovin]. AB - The authors describe their observations on the usage of the Hungarian biphasic contraceptive preparation Anteovin. 398 cycles of 42 women are follow-up. On the basis of the observations and subjective evaluation of the patients, the authors conclude that the preparation is well tolerated and is reliable, but is especially suitable for administration in women at the end of their reproductive period as well as in nonparous young women. PMID- 2100965 TI - [Colorectal carcinoma: epidemiology]. PMID- 2100966 TI - [Colonoscopy in neoplastic pathology of the colon]. PMID- 2100967 TI - [Immunologic and immunotherapeutic aspects of colonic carcinoma]. PMID- 2100968 TI - [Update on and perspectives of radiotherapy in the treatment of colonic carcinoma]. PMID- 2100969 TI - [Adjuvant chemotherapy of colorectal carcinoma]. AB - Clinical studies on adjuvant chemotherapy in colorectal cancer started 30 years ago, but some proof of its effectiveness did not come until recently. Only randomized prospective studies can provide definite evidence in this regard. Obviously, the potential value of an effective adjuvant treatment for a frequent disease such as colorectal cancer is enormous. Randomized studies had failed to provide evidence in favour of adjuvant chemotherapy in colon cancer until a recently reported study on 5-fluorouracil and levamisole. As of today, the latter regimen may be considered as the reference one for adjuvant chemotherapy in Dukes C colon cancer. In rectal cancer some studies displayed statistically significant results in favour of adjuvant chemotherapy: however, sufficient data are still unavailable to support adjuvant chemotherapy as standard treatment. On the contrary, postoperative radiotherapy is definitely effective in decreasing local relapses. Studies are underway on the combination of chemotherapy and radiotherapy in rectal cancer. In addition to systemic chemotherapy, portal infusion of cytotoxic drugs has been tested in colorectal cancer. Controlled studies are underway, but available results would not seem to support regional treatment. Recent improvement in the chemotherapy of advanced colorectal cancer has probably occurred through the pharmacologic modulation of 5-fluorouracil by leucovorin. If this will be confirmed, one will be able to resort to more effective multidrug regimens than those tested so far and an improvement in adjuvant chemotherapy may be anticipated too. PMID- 2100970 TI - [Multiple colorectal cancer]. PMID- 2100971 TI - Delayed cutaneous hypersensitivity after multiple injury and severe burn. AB - LetHality and overall prognosis after multiple injury and severe burn are determined to a major degree by the incidence and severity of infectious complications. Immunological reactions are influenced by the extent of trauma. Multitest Merieux is an appropriate and an easily applicable means to delayed hypersensitivity testing (DHT). This study investigates to what extent Multitest Merieux can help to predict the prognosis of multiply injured and severely burnt patients and whether new therapeutic measures can be recommended. This study encloses 52 patients during 1985: 16 severe burns, 20 multiple injuries with craniocerebral trauma and 16 without. Beginning with the day of injury standard laboratory and cardiopulmonary parameters were recorded every 48 hours. Delayed hypersensitivity testing was performed using Multitest Merieux. The extent of trauma was determined by help of the ISS. All quantitative laboratory and cardiopulmonary parameters showed no significant changes in correlation to the clinical course during the period under investigation. However, a significant correlation between Multitest reaction at days six and eight and its overall results and the rate of infectious complications was found. Moreover, the extent of trauma measured by ISS shows a positive correlation with the rate of anergic reactions in Multitest. Thus Multitest Merieux is an easily applicable and reliable means to the assessment of the prognosis after multiple injury and severe burn. Therapeutical recommendations beyond today's intensive care concepts cannot be given. PMID- 2100972 TI - [Barrett's esophagus: characteristics and evaluation of risk of malignancy]. AB - Barrett's esophagus (B.E.) is defined the replacement of the distal malpighian epithelium of the esophagus by a columnar type epithelium which is considered a precancerous condition. Its aetiology is supposed to derive from the damage induced by esophagitis. We recognize three endoscopic aspects of columnar replacement: flames or tongues of columnar epithelium in continuity to the gastric mucosa (I type), irregular cuff with malpighian islets (II type), complete circumferential cuff with displaced Z line (III type). The evolution of this epithelium into cancer is still debated (prevalence from 0 to 46%), but seems to be particularly elevated in presence of incomplete intestinal metaplasia (I.M.) in which the development of dysplasia is more frequent. The endoscopic examination is essential in the diagnosis and follow-up of B.E. Endoscopy permits other methodological approaches such as histological, chemical, ultrastructural examination aiming to obtain good results in the study of prevalence and incidence of esophagitis, B.E. and adenocarcinoma. It is also possible to perform functional examination. Many Authors joined international protocols to study B.E. in order to obtain uniform data about this condition. A second point of interest is represented by the evaluation of the efficacy of medical treatment to reduce the extension of Barrett's metaplasia and to control the esophagitis. Finally it is possible to detect fluorescence in the dysplastic tissues by laser irradiation using hematoporphyrin derivative and to evaluate their non surgical treatment with photodynamic therapy. PMID- 2100973 TI - [Merkel cell tumor]. AB - The authors review 274 cases of Merkel's cells tumor reported in literature and present one case they personally observed. This kind of neoplasm develops itself inside the derma without involving the epidermidis and shows an aggressive biological behaviour. The authors describe its anatomopathologic characteristics and underline the importance of the immunohistochemistry particularly for a differential diagnosis with respect to lymphoma, amelanotic melanoma and the scarcely differentiated metastatic carcinoma. Undoubtedly the surgical treatment is to be preferred. It consists of the removal of the primitive lesion together with a preventive regional lymphadenectomy. Radio and chemotherapy still don't play a standard role, their results are anyway encouraging even if not well defined up to now. These therapies are used in several ways: together with surgery in case of local relapses or metastasis or as sole treatment. In consideration of the small number of available data, we can finally state that Merkel's cells tumor must be further studied in order to come to a certain definition of this neoplasm from a histogenetic and anatomopathologic point of view and, above all, to find out a treatment able to reduce the high mortality rate that still today characterizes the prognosis. PMID- 2100974 TI - [Kidney failure during acute pancreatitis. A unique aspect of multiple organ failure]. AB - Eighty-two patients with acute pancreatis observed in the last seven years were included in prospective trial of monitoring protocol comprising: multiple organ failure and non invasive imaging of pancreatic lesion. One organ failure noted in the 60.9%, M.O.F. with three organ failure represented in the 21.9%. Renal failure was confirmed in 18.9%, trough nine clinical and biological index, become with shock in 73% and with extensive necrosis in 53%. ARF appeared with functional picture and normal diuresis in 73.3% and with organic failure in 26.7%. Index of specific mortality was 33.3%, while the comprehensive index of mortality in the study group was 12.9%, with a significant incidence in the half of deaths. PMID- 2100975 TI - [Alpha-1 inhibition. Clinical studies of the efficacy and tolerability of Alpress LP in mild to moderate essential hypertension]. AB - Alpress LP allows a continuous flow of prazosin, thanks to its new galenic form. This implies a better efficacy and less side-effects in the treatment of hypertension. Besides, prazosin being known for its favourable effect on hypercholesterolemia, Alpress LP was studied in this respect. In each of the three studies detailed thereafter, concerning hypertensive patients, proof was made of the efficacy and the good tolerance of Alpress LP, as compared to reference therapeutics given in hypercholesterolemia. PMID- 2100976 TI - [Alpha-1 inhibition. Prevention of coronary risk factors]. AB - Although diuretics and beta-blockers are efficient in treating high blood pressure and in decreasing the occurrence of strokes, these therapeutics have deleterious effects concerning lipidic metabolism, therefore worsening another cardiovascular risk factor. A comparative study evaluates the effects of prazosin and atenolol on plasmatic lipids of hypertensive patients. The results of this study confirm that prazosin can avoid an increase in plasmatic lipids. This therapy could therefore be prescribed to improve the ratio risk/benefit of the hypertensive therapy. PMID- 2100977 TI - Avoiding "death in the dental chair". PMID- 2100978 TI - Toward more rational nerve conduction interpretations: the effect of height. AB - One hundred four normal subjects ranging in age from 17 to 77 years and in height from 115 to 203 cm underwent nerve conduction studies of sural, peroneal, tibial, and median nerves. Foot temperature was measured in each patient. A strong inverse correlation was found between height and sural (r = -0.7104), peroneal (r = -0.6842), and tibial (r = -0.5044) conduction velocities. These correlations were significant at the P less than 0.001 level. Median conduction velocity was not correlated with height. Height was correlated with the distal latencies of all nerves studied (sural r = 0.6518, peroneal r = 0.4583, tibial r = 0.7217, median r = 0.5440). These correlations were significant at the P less than 0.001 level. Age was inversely correlated with both tibial (r = -0.4071) and median (r = -0.3464) nerve conduction velocities but not with sural and peroneal conductions. There were no correlations between distal latencies and age. If the variation in conduction velocity accounted for by the linear relationship with height was removed, then age would be inversely correlated to all conduction velocity measurements with the exception of the sural. Temperature is inversely correlated with the sural (r = -0.2233), peroneal (r = -0.2102), and tibial (r = 0.2710) distal latencies. In all instances, the effects of age and temperature were minor determinants when compared with the effects of height. Diagnostic conclusions made from nerve conduction data without correcting for height may be invalid in patients taller and shorter than normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2100979 TI - Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure. AB - The survival and ICU length of stay of 40 ARDS patients admitted to the ICU were analyzed to determine if a management strategy of lowering the pulmonary capillary wedge pressure (Ppw) was associated with an increased survival or a decreased ICU length of stay. ARDS was defined as three or four quadrant alveolar filling roentgenographically, a PaO2 less than 80 mm Hg with an FIO2 greater than .5 and a Ppw less than 18 mm Hg. Patients were divided into two groups: group 1 included all patients in whom there was a reduction of Ppw by at least 25 percent, and group 2 included patients in whom there was no, or less than a 25 percent reduction in Ppw. Survival was statistically different between the groups with 12 of 16 group 1 patients and seven of 24 group 2 patients surviving to hospital discharge. This difference remained statistically significant after stratifying patients by age and the APACHE II severity of illness index. We conclude that this retrospective analysis supports the notion that treatment of low pressure pulmonary edema with reduction of Ppw is associated with an increased survival. PMID- 2100980 TI - Leprosy in childhood. PMID- 2100981 TI - Prevalence and correlates of depressive symptoms in mothers of young children. AB - Mothers of young children are at risk for depressive symptoms due to their gender and status as parents. The primary purposes of this study were (1) to assess the prevalence of depressive symptoms in a sample of mothers with young children, (2) to identify sociodemographic correlates of depressive symptoms among the women, and (3) to determine if chronic stress is associated with depressive symptoms independent of other risk factors. In-home interviews were conducted with 196 mothers of 5- and 6-year-old children using the Center for Epidemiologic Studies- Depression (CES-D) Scale and the Everyday Stressors Index (ESI). High depressive symptoms (CES-D greater than or equal to 16) were reported by 49% of the mothers. They were highest among those who had never married, had less than a high school education, were under 25 years of age, were black, and had a low income. The ESI was a strong predictor of high depressive symptoms, controlling for sociodemographic characteristics. In comparison to mothers reporting a low level of everyday stressors (score = 5), those scoring 15 were 3 times more likely to have high depressive symptoms; those scoring 35 were more than 30 times as likely to have high CES-D scores. The results suggest the importance of chronic daily stressors as correlates of depressive symptoms in mothers of young children and also point to the need for multivariate models when examining predictors of those symptoms. PMID- 2100982 TI - The periodic health examination of older adults: the recommendations of the U.S. Preventive Services Task Force. Part I. Counseling, immunizations, and chemoprophylaxis. PMID- 2100984 TI - Universal New York Health Care. A single-payer strategy linking cost control and universal access. AB - Now that universal access to health care is back on the governmental agenda, elected officials are faced with the dilemma of expanding our present pluralistic system of numerous private and public payers, with its built-in administrative inefficiencies and inflationary pressures, or scrapping the present system of financing and moving to a tax-based scheme like the Canadian Medicare program, an option fraught with political difficulties. There is, however, a third option. The New York State Department of Health has developed a proposal for universal access--Universal New York Health Care, or UNY-Care--that would retain the existing payers, including employer-based insurance coverage, but combine them in a one-payer framework. Providers would no longer have to interact with the many public and private payers, each with its own rules, criteria, and levels of payment. The single payer would serve as the only payer for most health care services and would also negotiate reimbursement rates. The single-payer framework should bring savings in administrative and billing costs and should move government closer to the goal of buying health care services--getting good value for payment rendered--rather than simply paying bills as they are submitted. Although the single-payer strategy could be implemented at either the state or the federal level, it seems ideal as the principal responsibility of the states in a national plan for universal coverage. PMID- 2100983 TI - Addition of parenteral cefoxitin to regimen of oral antibiotics for elective colorectal operations. A randomized prospective study. AB - The efficacy of cefoxitin, a perioperative parenteral antibiotic, combined with mechanical bowel preparation and oral antibiotics to prevent wound infections and other septic complications in patients undergoing elective colorectal operations, was examined in a prospective randomized study. All 197 patients who completed the study received mechanical bowel preparation and oral neomycin/erythromycin base. In addition a perioperative parenteral antibiotic was given in three divided doses to 101 patients. The other 96 patients received no parenteral antibiotics. The overall incidence of intra-abdominal septic complications was 7.3% (7 of 96) in the control group (no cefoxitin) and 5% (5 of 101) in the treatment group (cefoxitin). This difference was not statistically significant. The incidence of abdominal wound infection was 14.6% in the control group and 5% in the treatment group, a statistically significant difference (p = 0.02). The addition of perioperative parenteral cefoxitin greatly reduced the incidence of wound infections in patients undergoing elective colorectal operations who had been prepared with mechanical bowel cleansing and oral antimicrobial agents. PMID- 2100985 TI - Unremarkable parotid tumours that prove to be malignant. AB - Of 539 patients with clinically unremarkable lumps treated by formal parotidectomy, subsequent histological examination indicated that 20 of these lesions were malignant. After a follow-up of 1-18 years, only one patient has suffered a recurrent tumour and none has died from disease related causes. The results indicate that formal parotidectomy is an acceptable means of treating the small number of malignant tumours presenting in this way, and strengthen the argument that attempts to obtain a histological diagnosis before treatment are contraindicated. PMID- 2100986 TI - Efficacy of prism adaptation in the surgical management of acquired esotropia. Prism Adaptation Study Research Group. AB - Prism adaptation, the preoperative use of prisms in acquired esotropia to determine the maximum angle of strabismus and to estimate fusional potential, has been suggested as a method of improving the results of initial surgery and minimizing the rate of reoperation. We performed a prospective, randomized, multicenter clinical trial of the effectiveness of prism adaptation. Two levels of randomization were used. Sixty percent of the patients underwent prism adaptation and 40% did not. Of those who responded to prisms with motor stability and sensory fusion, half underwent a conventional amount of surgery and half underwent augmented surgery based on the prism-adapted angle of deviation. Success rates were highest (54 [89%] of 61 patients) in prism adaptation responders who underwent augmented surgery and lowest (92 [72%] of 127 patients) in patients who did not undergo prism adaptation. Prism responders had better results with augmented surgery than with conventional surgery (54 [89%] of 61 patients vs 53 [79%] of 67 patients, P = .23). Our results indicated a significant beneficial overall effect of prism adaptation in patients with acquired esotropia (success rates, 83% vs 72%, P = .04). Although the process requires some additional time and effort, it appears to result in a higher rate of satisfactory alignment. PMID- 2100987 TI - Visual transduction in cones of the monkey Macaca fascicularis. AB - 1. Visual transduction in macaque cones was studied by measuring the membrane current of single outer segments projecting from small pieces of retina. 2. The response to a brief flash of light was diphasic and resembled the output of a bandpass filter with a peak frequency near 5 Hz. After the initial reduction in dark current there was a rebound increase which resulted from an increase in the number of open light-sensitive channels. The response to a step of light consisted of a prominent initial peak followed by a steady phase of smaller amplitude. 3. Responses to dim light were linear and time-invariant, suggesting that responses to single photons were linearly additive. From the flash sensitivity and the effective collecting area the peak amplitude of the single photon response was estimated as about 30 fA. 4. With flashes of increasing strength the photocurrent amplitude usually saturated along a curve that was gentler than an exponential but steeper than a Michaelis relation. The response reached the half-saturating amplitude at roughly 650 photoisomerizations. 5. The response-intensity relation was flatter in the steady state than shortly after a light step was turned on, indicating that bright light desensitized the transduction with a delay. This desensitization was not due to a reduction in pigment content. In the steady state, a background of intensity I lowered the sensitivity to a weak incremental test flash by a factor 1/(1 + I/IO), where IO was about 2.6 x 10(4) photoisomerizations s-1, or about 3.3 log trolands for the red- and green-sensitive cones. 6. Bleaching exposures produced permanent reductions in flash sensitivity but had little effect on the kinetics or saturating amplitude of subsequent flash responses. The sensitivity reductions were consistent with the expected reductions in visual pigment content and gave photosensitivities of about 8 x 10(-9) microns2 (free solution value) for the red and green-sensitive pigments. During a steady bleaching exposure the final exponential decline of the photocurrent had a rate constant given by the product of the light intensity and the photosensitivity. 7. In some cells it was possible to measure a light-induced increase in current noise. The power spectrum of the noise resembled the spectrum of the dim flash response and the magnitude of the noise was consistent with a single photon response roughly 20 fA in size. 8. The membrane current recorded in darkness was noisy, with a variance near 0.12 pA2 in the band 0-20 Hz.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2100989 TI - On mischief... PMID- 2100988 TI - Effect of surgery on the systemic inflammatory response to intermittent claudication. AB - The hypothesis that intermittent claudication initiates a systemic inflammatory response was investigated by studying the effect of exercise on markers of neutrophil activation and vascular permeability in 25 claudicants and 10 controls. Urinary albumin excretion, previously demonstrated to reflect vascular permeability, increased significantly after exercise in claudicants and was associated with decreased neutrophil filterability and increased serum lysozyme activity. No similar exercise-induced changes were seen in controls or in claudicants after successful arterial bypass surgery. These results suggest that intermittent claudication is associated with potentially deleterious systemic manifestations that are surgically reversible. PMID- 2100990 TI - The laryngeal mask airway in children. AB - The laryngeal mask airway was used in 200 children during a variety of surgical procedures. Some problem with the use of the device was encountered in 47 cases (23%), but in only five cases (2.5%) were the problems serious enough to warrant abandonment of its use. A clear airway was ultimately achieved in 191 children. Downfolding of the epiglottis over the laryngeal inlet was identified in eight out of 24 patients where flexible laryngoscopy was performed, clinically all these had unobstructed airways. The mask was used in 16 children with known airway problems. It is concluded that the size 2 laryngeal mask airway can be successfully used within the weight range 6-30 kg. PMID- 2100991 TI - Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. AB - BACKGROUND: A sudden increase in the incidence of post-transplantation lymphoproliferative disorder among the patients in our cardiac-transplantation program was temporally related to introduction of the immunosuppressive drug OKT3. This monoclonal antibody has come to be widely used in recent years both to prevent and to treat rejection after cardiac transplantation. METHODS: In order to identify variables that predict the development of post-transplantation lymphoproliferative disorder, we analyzed retrospectively a series of 154 consecutive cardiac-transplant recipients at a single institution. Univariate analyses and multivariate analysis by logistic regression were performed. RESULTS: Among 75 patients who did not receive OKT3, post-transplantation lymphoproliferative disorder developed in 1 (1.3 percent), as compared with 9 of 79 patients who received the drug (11.4 percent); the incidence among the OKT3 treated patients was ninefold higher (odds ratio, 9.5; 95 percent confidence interval, 1.6 to 54.7). According to multivariate analysis, the only factor significantly associated with the development of post-transplantation lymphoproliferative disorder was the use of OKT3 (P = 0.001). A significant increase in risk with increasing doses was also apparent: 4 of 65 patients who received a cumulative dose of 75 mg of OKT3 or less (6.2 percent) had post transplantation lymphoproliferative disorder, whereas 5 of 14 patients who received more than 75 mg had the disorder (35.7 percent; P less than 0.001). CONCLUSION: The addition of OKT3 to the immunosuppressive regimen increases the incidence of post-transplantation lymphoproliferative disorder after cardiac transplantation, and the risk increases sharply after cumulative doses greater than 75 mg. We suggest that the risks and benefits of prophylactic OKT3 administration be reassessed in the light of these findings, particularly since the value of prophylactic immunotherapy in cardiac-transplant recipients remains to be clearly established. PMID- 2100993 TI - Why HIV antibody testing is unpopular. PMID- 2100992 TI - Localization and characterization of the acrosomal antigen recognized by GB24 on human spermatozoa. AB - GB24, a mouse monoclonal antibody, recognizes a trophoblast-leukocyte cross reactive antigen (TLX), which is likely identical to the membrane cofactor protein (MCP), a complement regulatory protein. GB24 reacts also with a human acrosomal sperm antigen (Fenichel et al.: J Reprod Fertil 87:699-706, 1989). By immunofluorescence or immunoperoxidase, testicular, epididymal, and ejaculated spermatozoa were found to be positive after fixation by acetone. Motile, suspended spermatozoa became positive only through conditions known to induce acrosome reaction (A23187, follicular fluid, contact with oocytes). Ultrastructural studies with immunogold staining localized this protein on the inner acrosome membrane and in the acrosomal content. By SDS-polyacrylamide gel electrophoresis, GB24 immunoprecipitated a unique protein of 48 kDa from capacitated and A23187-induced spermatozoa under reducing conditions. No cross reactivity was found with mouse, boar, or ram spermatozoa. Localization of this human sperm antigen recognized by GB24 and its similarity with the TLX-MCP family antigens would suggest a possible role of this molecule during fertilization in sperm-egg binding or immune protection. PMID- 2100994 TI - The embryonic development of larval muscles in Drosophila. AB - Each of the abdominal hemisegments A2-A7 in the Drosophila larva has a stereotyped pattern of 30 muscles. The pattern is complete by 13 h after egg laying, but the development of individual muscles has begun with the definition of precursors at least by the onset of germ band shortening, some 5.5 h earlier. The earliest signs of muscle differentiation are cell fusions, which occur in the ventralmost mesoderm overlying the CNS and at stereotyped positions in the rest of the mesoderm as the germ band shortens. At the end of shortening, the pattern of muscle precursors produced by these fusions is complete. Precursors filled with dye reveal extensive fine processes probably involved initially in cell fusion and, subsequently, in navigation over the epidermis to form attachment points. The muscle pattern is formed before innervation and without cell death. Thus, neither of these processes is involved in determining the distribution of precursors. Evidence is presented for the view that the development of the larval muscle pattern in Drosophila depends on a prior segregation of founder cells at appropriate locations in the mesoderm with which other cells fuse to form the precursors. PMID- 2100995 TI - Inhibition of proteoglycan synthesis eliminates left-right asymmetry in Xenopus laevis cardiac looping. AB - The heart of any vertebrate is formed from an apparently symmetric cardiac tube that loops consistently in the same direction along the left-right axis of the embryo. In the amphibian Xenopus laevis, inhibition of proteoglycan synthesis by p-nitrophenyl-beta-D-xylopyranoside during a narrow period of development from late gastrula to early neurula specifically eliminated the looping of the cardiac tube. Most of the proteoglycans synthesized during this period were heparan sulfate proteoglycans. Treatment with p-nitrophenyl-alpha-D-xylopyranoside, an analogue that does not inhibit proteoglycan synthesis, did not interfere with cardiac looping. The critical period for proteoglycan synthesis was coincident with the migration of cardiac primordia to the ventral midline. The inhibition of cardiac looping was further explored in explants of cardiac primordia and anterioventral ectoderm. In recombinate embryos in which half the embryo, and thus one of the two heart primordia, was treated with p-nitrophenyl-beta-D xylopyranoside, and the other half was untreated, cardiac looping occurred normally. It is proposed that the left-right axis in Xenopus, as reflected in cardiac looping, is established early in development, and that proteoglycan synthesis is involved in the transduction of left-right axial information to the cardiac primordia during migration. PMID- 2100996 TI - The subunit structure of Saccharomyces cerevisiae transcription factor IIIC probed with a novel photocrosslinking reagent. AB - A photocrosslinking nucleotide, 5-[N-(p-azidobenzoyl)-3-aminoallyl]-deoxyuridine monophosphate (N3Rd-UMP), has been used to identify four polypeptides that are associated with the large Saccharomyces cerevisiae RNA polymerase III transcription factor TFIIIC, and to map the locations of these subunits along DNA when TFIIIC binds to the S.cerevisiae SUP4 tRNA(Tyr) gene. The 145 kd subunit of TFIIIC is primarily accessible to photocrosslinking from the vicinity of the box B + internal promoter element; 95 and 55 kd subunits are located on opposite sides of the DNA helix in the vicinity of the box A internal promoter element; a 135 kd subunit is less strongly crosslinked to the box A region and to a DNA segment between boxes B and A. DNA probes containing more than one N3RdUMP residue can form crosslinks between polypeptide chains. The specific circumstances of formation and the apparent mol. wts of two of these products lead to the tentative suggestion that a protomer of TFIIIC may contain two 95 kd subunits. PMID- 2100998 TI - Nucleotide sequence of the 5.8S and 25S rRNA genes and of the internal transcribed spacers from Arabidopsis thaliana. PMID- 2100997 TI - Synthesis and biological evaluation of 4-fluoro-, 7-fluoro-, and 4,7-difluoro-5,6 dihydroxytryptamines. AB - The 5,6-dihydroxytryptamine (5,6-DHT) derivatives 4-fluoro- and 7-fluoro-5,6-DHTs (26a,b) and 4,7-difluoro-5,6-DHT (26c) were synthesized from 3-fluoroanisole (1) and 1,4-difluoro-2,3-dimethoxybenzene (13), respectively. Efficient methods were developed for the conversion of 1 to 4-fluoro- and 7-fluoro-5,6 bis(benzyloxy)indoles (12a,b, respectively), and 13 to 4,7-difluoro-5,6-[( diphenylmethylene)dioxy]indole (19) via reductive cyclization of 2-nitro-beta (dialkylamino)styrenes prepared in situ from 2-nitrotoluenes. Indoles 12a,b and 19 were then converted to 26a-c via the corresponding indole-3-acetonitriles. The fluorine-substituted 5,6-DHTs displayed increased phenol acidities, determined spectrophotometrically, and decreased inherent potential to undergo oxidation as determined by cyclic voltammetry. Fluorine substitution did not have a significant adverse effect on the cytotoxic potential as judged from the IC50 values of 117, 125, 135, and 92 microM for 26a,c and 5,6-DHT, respectively, for the inhibition of incorporation of [3H]thymidine into the DNA of neuroblastoma clone N-2a cells in culture. Surprisingly, 26a-c exhibited 32-, 23-, and 13-fold higher affinities, respectively, compared to 5,6-DHT for the serotonergic uptake system of N-2a cells as measured by the ability of 26a-c and 5,6-DHT to antagonize the uptake of [3H]5-HT into the N-2a cells. These desirable chemical and biological properties of 26a-c should make them useful tools for the study of the molecular mechanism of neurodegenerative action of 5,6-DHT. PMID- 2100999 TI - Preparation, 252Cf-plasma-desorption mass spectrometry and radiometal exchange of the Pb2+ and Bi3+ complexes of a hexalactam macrocycle. AB - A macrocyclic tricatechol hexalactam ligand readily forms complexes with Pb2+ and Bi3+ ions. Solid samples were isolated and characterized by 252Cf-plasma desorption mass spectroscopy (252Cf-PDMS). Radioactive metal exchange studies employing 210Pb and 210Bi showed the compounds to be kinetically inert to exchange. The feasibility of using an available source of 203Pb, a potential imaging agent, with this class of compound was shown by synthesis of the labelled hexalactam complex. PMID- 2101000 TI - Nucleotide sequence of a cDNA encoding ammodytin L. PMID- 2101001 TI - Access to septanoside diacetals from methyl a-D-glucopyranoside. PMID- 2101002 TI - Structure and synthesis of an immunoactive lipopeptide, WS1279, of microbial origin. PMID- 2101003 TI - [Studies on the chemical constituents of Aquilaria sinensis (Lour.) Gilg. V. Isolation and characterization of three 2-(2-phenylethyl) chromone derivatives]. AB - Three 2-(2-phenylethyl) chromone derivatives were isolated from the ethyl acetate soluble fraction of the alcoholic extract of Aquilaria sinensis (Lous.) Gilg. (Thymeleaceae) by silica gel chromatography. Based on spectral data (UV, IR, 1HNMR, 13CNMR and MS) two of them are new compounds and their structures were identified as 5,8-dihydroxy-2-(2-p-methoxyphenylethyl) chromone (2) and 6,7 dimethoxy-2-(2-p-methoxyphenylethyl) chromone (3). The known compound siolated for the first time from this plant, was identified as 5,8-dihydroxy-2-(2 phenylethyl)-chromone (1). PMID- 2101004 TI - Hb J-Amiens [beta 17(A14)Lys----Asn] found in a Japanese. PMID- 2101005 TI - 4-Azido[3,5-3H]phenacyl bromide, a versatile bifunctional reagent for photoaffinity radiolabeling. Synthesis of prostaglandin 4-azido[3,5-3H]phenacyl esters. PMID- 2101006 TI - Management of drinking problems. PMID- 2101007 TI - Development of human fetal behavior: a review. AB - Most of the movements described during the course of gestation have already emerged before 16 weeks, and the presence of diurnal variation in human fetal behavior has been demonstrated from as early as 20 weeks gestation. Up to 26 weeks quiet intervals rarely exceed 5 min. After this age quiet intervals progressively increase in duration so that behavior appears cyclically rather than randomly distributed. Increasing linkage of the state variables results in identifiable fetal behavioral states from around 36 weeks. During the last trimester fetal activities are cycle- or state-dependent, so that prolonged, and often repeated, recording of behavior is necessary before any sinister conclusions can be drawn. PMID- 2101008 TI - Fetal tissue transplantation research. In support of the Moratorium. PMID- 2101009 TI - Fetal tissue transplantation research. Against the moratorium. PMID- 2101010 TI - Antenatal diagnosis and treatment of fetal bronchopulmonary sequestration. AB - Bronchopulmonary sequestration with associated nonimmune hydrops has been previously reported with generally poor prognosis for the neonate. We report a case of bronchopulmonary sequestration and associated pleural effusion successfully managed with a transthoracic catheter placement. The embryology and clinical pathophysiology of bronchopulmonary sequestration are discussed. PMID- 2101011 TI - Fetal lateral cerebral ventriculomegaly: associated malformations and chromosomal defects. AB - In 267 consecutive cases of fetal lateral cerebral ventriculomegaly, additional fetal malformations were detected by ultrasonography in 209 (78%) of the cases. On the basis of the ultrasound findings, the patients were subdivided into three groups: (i) isolated ventriculomegaly (n = 58), (ii) ventriculomegaly and open spina bifida only (n = 172), and (iii) ventriculomegaly and other malformations (n = 37) with or without spina bifida. Antenatal karyotyping was performed in 64 cases from groups (i) and (iii), and 11 (18%) of the fetuses had chromosomal abnormalities. The incidence of chromosomal abnormalities was strongly related to the presence of multisystem malformations. Thus, only 3% of fetuses with isolated ventriculomegaly as opposed to 36% of those with additional malformations had chromosomal defects. Furthermore, the degree of ventriculomegaly in the chromosomally abnormal fetuses was relatively mild. In the chromosomally normal fetuses, mild, static ventriculomegaly was associated with apparently normal subsequent mental development. PMID- 2101012 TI - Influence of cloprostenol-15-glycal on some hematologic values. AB - Cloprostenol-15-glycal is an analog of natural prostaglandin F2 alpha. It is prepared fully synthetically and is a basic substance of the veterinary medicament of firm name Glystrofan (chem. conc. Spolana, Neratovice, CSR). The effect of this substance was studied after intravenous application in double concentration on the blood cell count in experiment on rats. A significant decrease of erythrocyte count was observed in late sampling intervals especially after higher dose. A temporary elevation of leucocyte count occurred in white blood cell series. There was lymphocyte count elevation, while neutrophil count decreased. In the course of experiment a decrease of thrombocyte count occurred, especially after higher dose. Characteristic of described changes corresponds to that, which was observed by prostaglandins of series E. Changes in perifery blood cell count can be in agreement with the effect of cloprostenol-15-glycal on the production or influence of growth factors and on the proliferation of pluripotent hematogenic cells respectively. PMID- 2101013 TI - New imidazolylpyrazoles of potential pharmaceutical interest. AB - New imidazolylpyrazoles were synthesized and tested for antimicrobial activities. The compounds did not show any significant activity. PMID- 2101014 TI - [Informatics applied to the study of toxicology]. PMID- 2101015 TI - [The development of GMP in preclinical experimentation]. PMID- 2101016 TI - [Analytical characterization of cyclodextrin compounds for pharmaceutical inclusion. I]. PMID- 2101017 TI - [Dentistry in Colombia and Antioquia, 1960-1980]. PMID- 2101018 TI - [Teaching of orthodontics. Conclusions of the Colombian Orthodontic Association Commission]. PMID- 2101019 TI - [Dental atlas. Candidiasis]. PMID- 2101020 TI - [The need for a research climate. Reflections on science and technology]. PMID- 2101021 TI - [How to stimulate health/research in Colombia]. PMID- 2101022 TI - [Oral health status in Medellin. 20 years of integrated prevention]. PMID- 2101023 TI - [Diagnosis and proposed solutions to causes of stress in students in the clinic of the C.E.S. Health Science Institute Dental School]. PMID- 2101024 TI - [Protocol for evaluation of candidates for osseointegrated implants]. PMID- 2101025 TI - [Immunity in ophthalmology]. PMID- 2101026 TI - [Current concepts in malignant glaucoma]. AB - The paper reports on the main pathogenic types of anatomical blocking of the aqueous humor circulation in malignant glaucoma: pupillary, secondary iridolenticular, ciliovitreolenticular, iridociliovitreous blocks and in suprachoroidal effusion. The paper also presents some of the entities correlated with malignant glaucoma: glaucoma with blocked angle following the administration of miotics, traumatisms, the operations of scleral obstruction for retina detachment, panretinal photocoagulation and thrombosis of the retina central vein. PMID- 2101027 TI - [Mixed glaucoma--a separate entity?]. AB - The author affirms the existence of the mixed forms of glaucoma, starting from the glaucoma classification according to the gonioscopic criterium. He shows that this classification is based on the anatomic constitution and the angle cannot be open and closed at the same time. The so-called mixed glaucomas are, in fact, either different evolution stages of one of the two forms admitted or secondary glaucomas. PMID- 2101028 TI - [Supplementary concepts in the physiopathology of the vitreous]. AB - The normal vitreous defends the posterior pole damping the traumatic and tension shocks coming from the anterior pole reducing their intensity according to formula P = F/S The buffering function decreases in direct proportion to the degree of fluidity of the vitreous, fluidity that enlarges the volume of the vitreous whereas the mass does not change according to the density formula p = m/v, the density of the liquefied vitreous being greatly diminished. The liquefied vitreous may lead to degenerative lesions of the retina due to prolonged tension of the retina resulting in ruptures and detachment. An anterior pole pressure of 15-16 mmHg transmitted non-modified to the posterior pole through the liquefied vitreous, exceeding by far the pressure of the opticoretinal tissular fluid pressure which in 9 mmHg leads to papillary excavation and glaucoma without tension; hence the liquefied vitreous must be replaced by a normal one or its density built up again. PMID- 2101029 TI - [The ergo-ophthalmological problems raised by work at video terminals]. AB - The paper reports a study on the involvement of the visual system during work at video terminal. The results of the investigations on a group of operators in a computation centre were used for describing an optimum anatomicofunctional visual type for work at video terminal and the hygiene rules to be observed during work at the computer screen. PMID- 2101030 TI - [Variable pressure changes (+/-) in the anterior ischemia syndrome--the elements of a reserved prognosis in the surgery of retinal detachment]. AB - The authors show that the variations of intraocular hyper- and hypotension stand for a reserved prognosis in the evolution of the operated retina detachment. Likewise, they consider that the repeated operations in the retina detachment may lead to the syndrome of anterior ischemia, unfavourable to the visual function. PMID- 2101031 TI - [Aspirin in the preventive treatment of cataract]. AB - In the patients with rheumatoid arthritis treated for a long time with aspirin, the percent of cataract is very low. Three action ways of aspirin were formulated in hindering the appearance of cataract: 1) acetylation of the lens proteins; 2) decrease of glycemia and 3) decrease of triptophen amount in the blood plasma. The lab experiments plead for these hypotheses. For preventing cataract, the persons with high risk of cataract and with incipient signs of opacity are recommended a daily and long treatment with 1/2 buffered and effervescent aspirin tablet, or 1 tablet at two days, under careful ophthalmologic surveillance. PMID- 2101032 TI - [A comparative study of the ocular hypotonic action of collyria with oxprenolol and timolol maleate]. AB - Comparison of the decrease in intraocular tension in a group of 25 patients show that the collyria of oxprenolol, 0.25%, led to an average decrease of 6.36 mmHg, whereas that of thymolol maleate, 0.25%, to a decrease of 8.76 mmHg. Both decreases were statistically significant versus the initial intraocular tension. PMID- 2101033 TI - [The treatment of posttraumatic endophthalmia]. AB - Starting from a case of endophthalmitis secondary to a stung plague, the authors show the present treatment trends in this ophthalmic disease. The paper also reports on the importance of intravitreous administration of antibiotics associated or not with vitrectomy, corticotherapy, and other adjuvant treatments and on the possible complications induced by this new therapeutic trend. PMID- 2101034 TI - [Recurrent traumatic keratitis due to an overlooked conjunctival foreign body]. PMID- 2101035 TI - [Bilateral occlusion of the venous arm]. AB - The paper reports on a clinical case of occlusion of retinal venous arm in both eyes, at a time interval of 6 months, the right eye being the former affected. The clinical observation showed the following: symmetrical topographic sites (superotemporal venous arm); existence of arteriovenous crossing in the occlusion site; ischemic capillaropathy with serious macular involvement. The clinical and lab examinations did not show pathogenic elements. The paper discusses largely on the role of arteriovenous crossing and of arteriosclerosis in the pathogeny of affection, the visual prognosis and on some therapeutic considerations. PMID- 2101036 TI - [The Reese syndrome. Anatomicoclinical and therapeutic considerations]. AB - The paper presents two clinical cases of complex iridocorneal disgenesis with glaucoma and ectodermal anomalies followed for a period of several years. The cases underwent antiglaucomatous surgery that afforded a good visual preservation and an optimum intraocular pressure. PMID- 2101037 TI - [Congenital glaucoma]. PMID- 2101039 TI - [Data on unilateral congenital cataract]. PMID- 2101038 TI - [Hyphema, a risk factor in the glaucomatous eye]. AB - A hemorrhage in the anterior chamber is a frequent phenomenon, very often treated too easily. Our investigation followed for 3 years (1985-1987) the way in which hyphema were resorbed after the eye contusions in the patients operated by cataract or glaucoma. The causes of hyphemas, their onset, the aspect of the blood and the resorption period are analyzed. The majority of hyphemas were resorbed in the first 7 days (in the case of contusions 87%, after operation of cataract 84%) but in the glaucomatous patients the resorption in the first 7 days appeared only in 50% of the cases; the blood remained in the anterior chamber in 12.5% of cases even after 21 days. The blood in the anterior chamber is resorbed by the excretory ducts, mainly as intact erythrocytes; in the glaucomatous patients the ducts are altered and the erythrocytes are more difficulty eliminated. The liquid in the anterior chamber is eliminated by the fistulization opening, but the erythrocytes do not pass as they cannot be resorbed in the subconjunctival space. The blood in the anterior chamber of an eye with ocular hypertension (decompensated glaucoma or contusions with hypertension) favours the hematic impregnation of the cornea, and the macrophages loaded with hemosiderin are deposited at the level of the excretory ducts, thus increasing the danger of hemolytic secondary glaucoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101040 TI - [The morphopathological aspects of the trabecula in glaucoma]. AB - The authors tackle, using the methods of classic histology, an important practical medical problem, the affection of the corneoscleral trabecula in different clinical forms of glaucoma. A study of the age-related trabecular modifications is also made. All the clinical forms of glaucoma present lesions corresponding to the evolution stage of the disease. No morphologic differences were noticed between these forms and the alterations met are similar to the senile trabecula. PMID- 2101041 TI - [The reasons for failure in retinal detachment]. AB - Detachment of the retina is still a very serious ocular disease which poses many problems to the ophthalmologist. The study shows the causes of the treatment failure in this disease on the basis of the authors' experience and the specially literature. PMID- 2101042 TI - [Charleux's method of basal iridectomy]. AB - Retrograde transcorneal iridectomy suggested by Charleux and Etienne was used in 27 eyes (20 patients) suffering from glaucoma with closed angle (in 12 eyes with acute attack and in 15 congeneric eyes) (prophylactic). The post- or intrasurgical complications were absent. The operation was simple and had good results. The hospitalization period was of 2-3 days. PMID- 2101043 TI - [Primary malignant glaucoma]. AB - The authors present two cases of classical unilateral malignant glaucomas, having at the congeneric eye, a chronic primary glaucoma with extremely advanced blocked angle. The evolution of these two cases might indicate the possibility of transforming the chronic primary glaucoma with blocked angle into a primitive malignant glaucoma (spontaneous). The probable dynamics of these changes is described. PMID- 2101044 TI - [Pigmentary retinopathy and Coats' vasculopathy]. AB - The paper reports on a clinical case of association between pigmentary retinopathy and Coat's retinal vasculopathy. The study of the clinical syndrome of the case presented and of those described in the literature, shows the possibility that vascular telangiecstases might be the consequence of a hereditary tendency towards a form of latent vasculopathy, that develops towards a known clinical form. The disturbances of a generalized retinal vascular permeability, described for the first time in this context seems to be dependent on the genetic type of pigmentary retinopathy and independent of the peripheral telangiectatic modifications. The association of the two affections is, by the serious complications they generate, a factor of aggravating the visual prognosis. PMID- 2101045 TI - [Iatrogenic glaucoma]. AB - Many preparations used in the therapy of different general affections have as side effects the appearance of ocular hypertonia and several incidents and accidents connected by the surgery. The authors considered important to discuss on this medical aspect of great interest, with emphasis on the interdisciplinary co-operation and on the accuracy of the medico-surgical ophthalmologic gesture. PMID- 2101046 TI - [Romanian contributions to achieving expert systems in different eye diseases]. PMID- 2101047 TI - [Low-pressure glaucoma (a clinico-statistical study)]. AB - Study of 50 cases of glaucoma with low pressure shows a frequency of the affection in 6.39% of the cases of glaucoma with open angle. In 75% of the cases, glaucoma with low pressure appears after the age of 60, with distinct predominance in females. In 10% of the cases this glaucoma was hereditary. For the diagnosis of glaucoma with low pressure, the systematic research of the ocular tension, stimulation of provocative tests, and the examination of the visual field and of the optic papilla, are of great use. The presence in the same family of the glaucoma with open angle with high tension, of that with low tension shows that the low pressure glaucoma is not a special form of glaucoma. It is the result of a circulatory insufficiency at the level of papilla of the optic nerve, with the appearance of characteristic functional deficiencies, even where the ocular tension is apparently within normal limits. PMID- 2101048 TI - [Antibiotic stability in magistral collyria]. AB - The paper presents the results of a study on physicochemical and and microbiological stability of collyria with such antibiotics as: Kanamicin, Oxacilin, Colistin, Erythromycin and Rifampicin. The authors insist on the necessity of preparing the ophthalmic solution with the antibiotics studies, with solvent for eye drops as provided for by RF IX and keeping at +4 degrees C, at dark. PMID- 2101049 TI - Praziquantel inhibits Schistosoma mansoni attachment in vitro. AB - Male adult Schistosoma mansoni worms were placed in a glass dish containing Tyrode solution and observed for 15 min after addition of praziquantel (0.01 to 1 microM). Praziquantel promoted a concentration- and time-dependent inhibition of sucker-mediated attachment of the worm. Attachment inhibition was correlated with shortening of the parasite. We propose that the rapid and total inhibition of worm attachment observed in vitro with 1 microM praziquantel indicates that therapeutic concentrations of this drug should promote a rapid hepatic shift, in vivo, which may facilitate host tissue reaction. PMID- 2101050 TI - Pleural eosinophil infiltration induced by PAF-acether is not a desensitizable phenomenon. AB - This study investigated the effect of successive daily intrathoracic (it) injections of PAF-acether upon its demonstrated ability to generate eosinochemotaxin(s). Repeated administration of PAF-acether led to a selective state of desensitization, characterized by a gradual reduction of its ability to induce exudation. Concomitantly, however, there was a progressive pleural accumulation of eosinophils leading to a 7-fold increase in the eosinophil counts after the 4th restimulation. The generation of eosinochemotaxin(s) elicited by PAF-acether was not modified by desensitization, as detected by transferring the cell-free pleural fluid from donor to recipient animals. We conclude that, in contrast to exudation, eosinophil tissue infiltration induced by PAF-acether is not a desensitizable phenomenon. PMID- 2101052 TI - Effect of clonidine on growth and plasma somatomedin C levels of young rats. AB - To study the effects of clonidine on growth and plasma somatomedin C (SmC) levels, 42 male Wistar rats aged 28 days and weighing 75 to 105 g were given clonidine (1.5 micrograms/ml in drinking water), or filtered water alone and were weighed weekly. After 0, 4 and 8 weeks, the animals were sacrificed under ether anesthesia, their length was measured and blood was collected by cardiac puncture for measurement of SmC concentration. Growth and the weight/length ratio were lower, and plasma SmC levels (mean +/- SEM) were greater in the treated groups after 4 (616 +/- 44.7 vs 433.2 +/- 39.38 ng/ml, P less than 0.01) and 8 (595.2 +/ 28.3 vs 412.66 +/- 39.01 ng/ml, P less than 0.01) weeks of treatment, suggesting that clonidine treatment increased growth hormone secretion. In other experiments, treated animals showed increased food intake only during the first week of treatment and decreased epididymal fat weight after 3 weeks (1.412 +/- 0.0536 vs 1.6 +/- 0.1336 mg/100 g body weight, P less than 0.01). The results suggest that clonidine acts at the level of the central nervous system involving transitory modulation of food intake, as well as on the regulation of energy metabolism. PMID- 2101051 TI - Locomotor activity and one-way active avoidance after intrahippocampal injection of neurotransmitter antagonists. AB - Sixty-three rats with previous training in a T-maze, bilaterally implanted with cannulae directed toward the dorsal hippocampus, were used in this study. All rats received bilateral 1-microliter injections 20 min before testing for locomotor activity (day 1) and one-way active avoidance (day 3). The following drugs were injected into groups of 4 to 8 animals: scopolamine (9 or 18 micrograms/microliters), propranolol (5 or 10 micrograms/microliters), cimetidine (0.75 or 1.5 micrograms/microliters), sulpiride (5 or 10 micrograms/microliters), or vehicle (Krebs-Ringer). Locomotor activity was not changed by injection of any drug. However, intrahippocampal injections of scopolamine (9 micrograms/microliters) and sulpiride (10 micrograms/microliters) impaired avoidance behavior, particularly during the last five trials of the task. We conclude that muscarinic-cholinergic and D2-dopaminergic, but not beta-adrenergic or H2-histaminergic, mechanisms in the hippocampus are involved in the performance of one-way active avoidance behavior. PMID- 2101053 TI - Accessory optic-pretectal interactions in the pigeon. AB - This electrophysiological study analyzes the influence of the nucleus of the basal optic root (nBOR) of the avian accessory optic system on units within the lentiform nucleus (LM), which is the avian equivalent of the pretectal nucleus of the optic tract. A prominent depression of the spontaneous firing rate of neurons within the LM occurred following electrical stimulation of the ipsilateral nBOR. A close correlation was also found between the directional selectivity of LM units and the apparent displacements generated by rotations of the head around the horizontal semicircular canal axis. This is consistent with a possible role of the LM in the coordinate transformation from visual inputs to a vestibular reference system. PMID- 2101054 TI - Stress-induced desensitization of the cardiovascular response to noradrenaline in unanesthetized rats. AB - The present study was undertaken in order to analyse the effect of swimming stress on the blood pressure response to noradrenaline (NA) in unanesthetized rats. Swimming induced a desensitization of the blood pressure response to NA which was not blocked by previous animal treatment with prazosin (0.1 mg/kg). However, rats submitted to stress showed increased sensitivity to the prazosin blocking effect. The results suggest that swimming-induced desensitization of the cardiovascular response to NA is mediated by alpha rather than beta-1 adrenoceptors. PMID- 2101055 TI - Electrical activity of the posterior thalamic nucleus and the hippocampus during wakefulness and desynchronized sleep in the rat: a spectral analysis. AB - The electrical activity of the posterior thalamic nuclear complex was studied in rats and related to the simultaneous hippocampal electro-oscillogram. Electrocorticographic tracings and spectral analysis showed that during attentive wakefulness the electro-oscillogram peaked at 8 Hz and in desynchronized sleep it oscillated at regular frequencies between 8 and 9 Hz. In quiet wakefulness, frequency was lower (around 6 Hz) and during synchronized sleep rhythmicity disappeared. The electrophysiological patterns during wakefulness and desynchronized sleep are proposed to be linked to the retrieval and combination of information for the generation of attention and dream content. PMID- 2101056 TI - Efferent projections of the pigeon intergeniculate leaflet containing neuropeptide Y. AB - The present study was preformed to map efferent projections of the pigeon intergeniculate leaflet (IGL) to other visual structures, with emphasis on the pathways containing neuropeptide Y (NPY). After injections of an anterograde tracer (Phaseolus vulgaris leucoagglutinin) into the IGL, labeled axons and presumptive terminals were seen in several retinorecipient and visually-related nuclei. All such areas contained immunoreactive fibers to antibodies against NPY. Electrolytic lesion of the IGL provoked a marked reduction in the number of NPY labeled fibers in these visual structures. The data suggest that the IGL is the source of NPY-labeled axons which occur in many visual nuclei of the pigeon brain. PMID- 2101057 TI - Evidence for recrossing of the pathway from the retina to the ipsilateral nucleus of the optic tract. AB - Single-unit recordings of the nucleus of the optic tract (NOT) under visual stimulation were performed in 5 opossums. Most of the units were directionally selective. Receptive fields for the contralateral eye lie mainly in the contralateral field while those for the ipsilateral eye were mainly in the ipsilateral field. As the nasal retina does not project ipsilaterally, recrossing must occur in the pathway from the retina to the ipsilateral NOT. Possible sites for this recrossing are discussed. PMID- 2101058 TI - Stationarity and normality of distribution of rat cortical brain waves. AB - Establishing the stationarity and statistical distribution of potentials recorded from the nervous system is crucial for the application of frequency analysis. Both parameters were determined in the electrocorticograms of six adult Wistar rats during wakefulness and desynchronized sleep, during both of which desynchronization prevails. Stationarity of the signals was found to occur during at least 20 s in both states of the wakefulness-sleep cycle. A normal distribution was also found for at least 6.7 s. These findings provide strong support for the use of frequency analysis of brain waves as a reliable method to quantify neural electro-oscillograms. PMID- 2101059 TI - Psychophysiological effects and dose equivalence of zopiclone and triazolam administered to healthy volunteers. Methodological considerations. AB - 1. Dose-equivalence studies of zopiclone and triazolam were carried out. 2. Zopiclone (6.25, 8.75 and 11.25 mg), triazolam (0.1875, 0.375 and 0.5 mg) and placebo were given in the morning to 14 healthy male volunteers aged 20-25 years under double-blind conditions according to an incomplete block design. Each patient received three of the seven possible treatments at intervals of at least 1 week. Subjects were evaluated using physiological measures, rating scales and memory tasks before and 1.5 and 4.5 h after drug administration. 3. The sedative and amnestic effects of zopiclone were qualitatively similar to those of triazolam, with the highest dose of each having the greatest effect. 4. On the basis of the digit symbol substitution test, 10 mg of zopiclone is equivalent to 0.5 mg of triazolam. Methodological problems of the experimental design of dose equivalence studies are discussed. PMID- 2101060 TI - Association of specific histocompatibility antigens and acanthosis nigricans with insulin resistance. AB - 1. The association or interaction of histocompatibility antigens (HLA) and acanthosis nigricans with type A insulin resistance was studied in 13 patients (10 from family I, 2 from family II and an isolated case) for both sexes. 2. HLA typing for the A, B, C and D antigens was performed by a standard microcytotoxicity test for all patients and for 100 normal controls from the same geographic area. 3. The frequency of HLA B8 was 21% in the control group and 100% in patients with acanthosis nigricans. The frequency of HLA A1B8 was 15% in controls and 73% in acanthotic patients. 4. All the members of family I presenting the association of a possible insulin receptor defect (most likely provided by patient 2) with HLA B8 (provided by patient 1) showed a more pronounced clinical and laboratory expression of insulin resistance. 5. These data suggest that class I antigens of major histocompatibility complex (MHC), A1 and/or B8, may be involved in the pathogenesis of some forms of insulin resistance such as acanthosis nigricans (type A syndrome), possibly by a molecular interaction of the antigens with insulin receptors. PMID- 2101061 TI - Effects of caffeine on the rate of perceived exertion. AB - The role of caffeine in improving performance in endurance exercises is controversial and its mechanism of action is not well understood. The purpose of the present study was to evaluate the effects of caffeine on the rate of perceived exertion (RPE) by exercising athletes. Six male non-smoking runners, aged 26.8 +/- 4.9 years (mean +/- SD), who had been in training continuously for at least two years before the experiment were studied. Mean maximum oxygen consumption (VO2max) was 61.21 +/- 5.36 ml kg-1 min-1. The subjects were asked to exercise on a bicycle ergometer for 3 min each at 300 and 600 kg m min-1, after which the work load was elevated to 1200 kg m min-1 and they exercised until exhaustion. In order to evaluate the effects of caffeine, the exercise was performed twice following the ingestion of 200 ml decaffeinated coffee with and without caffeine (5 mg/kg body weight). Caffeine had no significant effect on exercise time, pulmonary ventilation, oxygen consumption, carbon dioxide extraction or exchange respiratory ratio, but the RPE was significantly lower (P less than 0.05) at the work load of 1200 kg m min-1 after the ingestion of caffeine for both trials I and II. The present results suggest that metabolic acidosis and glycogen depletion were not the main causes of exhaustion. PMID- 2101062 TI - Effects of chronic treatment with high doses of chlorpromazine on ATP and ADP hydrolysis by synaptosomal fractions from the rat caudate nucleus. AB - Several studies have indicated that chlorpromazine and its metabolites affect ATP hydrolysis by brain and liver plasma membranes in vitro. The present report examines whether chronic treatment (12 days) with high doses of chlorpromazine (10 and 40 mg/kg) could affect ATP and ADP hydrolysis by synaptosomal fractions from the rat caudate nucleus. Both doses of chlorpromazine caused significant and parallel decreases (23 to 31%) in the ATP and ADP hydrolysis. The parallelism between the effects of chlorpromazine on ATP and ADP hydrolysis suggests the participation of a single enzyme (ATP diphosphohydrolase) in nucleotide hydrolysis. PMID- 2101063 TI - Effect of caffeine administration on latent learning ability of male rats in a simple maze task. AB - Animals can acquire information about the environment in the absence of conventional rewards. This latent or incidental learning depends on their interaction with the environment. The present report examines whether caffeine (120 mumol/kg) could enhance latent learning of a simple maze task by increasing exploratory activity of rats in the maze. Though caffeine increased the activity of rats in the maze under a nonappetitive condition, methylxanthine did not improve performance in rats tested under an appetitive condition in the maze. These results suggest that caffeine (120 mumol/kg) does not facilitate latent learning of a simple maze task. An interesting and unexpected finding of the present study was that caffeine caused greater stimulation of exploratory activity in the open-field than in the maze under nonappetitive conditions. This may be due to differences in the complexity of the two paradigms. PMID- 2101064 TI - Local administration of interleukin-1 increases sensory neuron regeneration in vivo. AB - The proximal and distal stumps of severed mouse sciatic nerves were inserted into opposite ends of polyethylene tubes. The tubes were implanted either empty or filled with collagen alone or in combination with interleukin-1 (IL1). Six weeks later, neurons in the L3-L5 dorsal root ganglia were back-filled with HRP. The number of HRP reactive sensory neurons detected in the IL1-treated animals was significantly greater than that seen in the other experimental groups. Thus, exogenous IL1 may partially mimic the effects obtained with in vivo administration of nerve growth factor in protecting sensory neurons from lesion induced death. PMID- 2101065 TI - Stereoselectivity of the anxiolytic effect of propranolol microinjected into the dorsal midbrain central gray. AB - In a previous study we have shown that microinjection of d,1-propranolol into the dorsal midbrain central gray of the rat causes an anxiolytic effect in the elevated plus-maze model which is likely to be mediated by endogenous 5 hydroxytryptamine. In the present experiment, the effects of 1- and d,1 propranolol were compared under the same experimental conditions. Both the 1 isomer and the racemic mixture increased the percentage of open arm entries without affecting the total number of entries into either open or enclosed arms of the maze, thus reproducing the selective anxiolytic effect previously described. The doses of 5 nmol 1-propranolol and 10 nmol d,1-propranolol caused anxiolytic effects of comparable magnitude, while the doses of 2.5 nmol of the former and 5 nmol of the latter were ineffective. Therefore, the 1-isomer was nearly twice as potent as the racemic mixture, thus being responsible for the pharmacological activity observed. These results are compatible with the proposal that propranol blocks stereospecific autoreceptors in serotonergic nerve endings that inhibit neurotransmitter release. PMID- 2101066 TI - Serum transaminase levels in the acute phase of chronic extrahepatic cholestasis. AB - Serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) levels are normal or discretely increased in rats with chronic extrahepatic cholestasis (CEHC). During the acute phase (first 72 h after biliary obstruction), however, serum transaminase values are quite elevated due to a mechanism not yet fully elucidated. Thus, this is a good experimental model, not involving hepatocellular necrosis, for the study of serum ALT and AST levels during the acute phase of CEHC. Male Wistar rats (250-350 g) were divided into two groups: group A (N = 60) was submitted to sham operation for bile duct ligation (BDL), and group B (N = 60) was submitted to BDL. Thirty and 120 min after BDL there was a 1.5-fold increase in both serum ALT and AST levels compared to sham-operated rats (P less than 0.05). Serum ALT levels were higher than AST levels as early as 30 min after BDL and the highest serum values for both transaminases were observed at 360 min which was also the last value measured. Serum AST levels increased 120 min after BDL, with no further significant increases thereafter. PMID- 2101067 TI - Chlorthalidone alters the vascular reactivity of DOC-salt hypertensive rats to norepinephrine. AB - Hypertension caused by deoxycorticosterone-salt (DOC-salt) may involve enhanced sympathetic tone and some diuretics may exert their antihypertensive action by modulating presynaptic adrenergic sensitivity. This study analyzes the noradrenergic sensitivity of the perfused mesentery isolated from DOC-salt hypertensive rats treated or not with chlorthalidone. Chlorthalidone treatment reduced arterial hypertension in DOC-salt treated rats (from 160 +/- 7 to 127 +/- 5 mmHg). The diuretic completely prevented the increase in sympathetic tone and blunted the decreased vagal tone observed in DOC-salt rats. Norepinephrine induced vasoconstriction was enhanced in perfused mesenteries isolated from DOC salt rats. This alteration was attenuated in preparations from chlorthalidone treated DOC-salt animals. Blockade of neuronal catecholamine uptake using cocaine did not change these responses. These data suggest that chlorthalidone reduces the vascular hyperresponsiveness to catecholamines observed in DOC-salt treated hypertensive rats. PMID- 2101068 TI - Plasma kallikrein clearance by the liver in food-restricted rats. AB - We measured the clearance rate of plasma kallikrein by the liver in three groups of rats: one recently weaned, and two seven weeks old (control and food restricted groups). The clearance rates were similar in the three groups when expressed as units/g liver. The livers of the recently weaned and food-restricted rats were, however, smaller than those of the controls and consequently their livers cleared plasma kallikrein less efficiently. PMID- 2101069 TI - Absence of zinc cytotoxicity. Effect of short-term zinc oral administration on rat gastric mucosa. AB - Zinc ions have been reported to stabilize cellular membranes, protecting the gastric mucosa against a wide variety of ulcerative agents. The treatment with zinc sulfate intragastrically administered as one dose (20 mg/kg body weight) daily for 30 consecutive days did not modify the normal aspect of rat gastric mucosa as observed by electron scanning microscopy. Furthermore, the X-ray microanalysis of the lysosome content performed on different gastric mucosa cells did not show the zinc element. These results suggest that zinc ion is a relatively nontoxic element for the rat gastric mucosa. PMID- 2101070 TI - Effect of the quantity of dietary amino acids on egg production and layings by ceratitis capitata (Diptera, Tephritidae). AB - 1. Diets containing different amounts of an amino acid mixture were tested in terms of egg production and layings by Ceratitis capitata. The amino acid composition of the diet was identical to that of casein. The other components of the diet were: 1.0 g agar, 0.8 g of a salt mixture, 0.8 g of a vitamin mixture, 1.6 g corn oil, 0.2 g Tween 80, 0.5 ml propionic acid, 90 ml distilled water and 0.5 ml of a 20% alcohol solution of nipagin. Diets containing 0.4, 0.8, 1.2, 1.6 and 2.0 g of an amino acid mixture per 100 ml diet and an amino acid-free control diet were used. The diets were made isocaloric by adding 12.4, 12.0, 11.6, 11.2 and 10.8 g sucrose, respectively. 2. The diet containing 1.2 g amino acids proved to be the best, leading to 6.84 egg layings per female per day and to production of 7.72 eggs per female per day. PMID- 2101071 TI - Effects of toluene exposure during gestation on neurobehavioral development of rats and hamsters. AB - Pregnant rats and hamsters were exposed to toluene vapor (800 mg/m3) 6 h daily from gestation days 14 to 20, and 6 to 11, respectively. Growth, neuromotor development and performance of the offspring in behavioral tasks were assessed. In rats, toluene exposure increased the number of litters with low birth weight pups. Male rat offspring exposed to toluene displayed shorter latencies than male controls to choose one side of a T maze in a spontaneous alternation test. Hamsters exposed to toluene performed worse in a rotating rod test. These results confirm toluene fetotoxicity in rats and suggest an effect on exploratory behavior which may be related to hormonal changes in early life. Neuromotor effects of exposure of hamsters to toluene in utero deserve further investigation. PMID- 2101072 TI - Observations on the arrangement of axons according to diameter in the optic tract of the opossum Didelphis marsupialis. AB - The spectra of fiber sizes at different depths of the optic tract of the opossum Didelphis marsupialis were examined by electron microscopy in order to test for correlations between the eventual location of axons and relevant developmental events. Frequency histograms showed 1) a predominant representation of medium sized axons and the virtual exclusion of coarse fibers from the deepest portion of that pathway, and 2) a progressive increase in the proportion of thin axons from deep to superficial sites of the tract. These findings are discussed in terms of the view of the optic tract as a chronological map of axon arrival. PMID- 2101073 TI - Effect of hepatic artery ligation in rats with chronic extrahepatic cholestasis. AB - Because of the liver's dependence on arterial blood to exert its metabolic functions in cirrhosis of the liver, with or without thrombosis of the portal vein, the interruption of hepatic arterial flow for the palliative treatment of malignant tumors of the liver is counterindicated. However, the effects of arterial devascularization on the cholestatic liver are not fully understood. The objective of the present study was to investigate hepatic alterations due to hepatic artery ligation in rats with chronic extrahepatic cholestasis. Serum alkaline phosphatase, bilirubin and alanine aminotransferase were measured in rats 3 h after sham operation (group A, N = 29) or ligation of the hepatic artery (group B, N = 29). Alanine aminotransferase activity was significantly higher (P less than 0.05) in group B, demonstrating acute hepatocellular damage in animals with chronic extrahepatic cholestasis. PMID- 2101074 TI - Ethanol decreases choice accuracy in a radial maze delayed test. AB - 1. The effect of acute ethanol on memory was studied in an eight-arm radial maze by interposing a 15-s or 1-h delay between the rat's fourth and fifth arm choices. 2. Ethanol (1.0 g/kg) was injected intraperitoneally 5 min prior to the first set of 4-arm choices, therefore being present since the acquisition of the trial-unique event. 3. The results showed 1) a decrease in choice accuracy only in the final 4 arm choices after the 1-h delay, and 2) that errors consisted of re-entries into arms chosen before the delay was imposed. The data further support the contention that ethanol impairs retention of working memory. PMID- 2101075 TI - Identification of T-cell reactive antigens in Nippostrongylus brasiliensis using a cell immunoblotting technique. AB - Antigens of the nematode Nippostrongylus brasiliensis were fractionated by SDS PAGE under reducing conditions, transferred electrophoretically onto nitrocellulose and converted to antigen-bound nitrocellulose particles for use in in vitro proliferation assays. Mesenteric lymph node cells from infected rats were analyzed for reactivity against the fractionated antigens, revealing a range of different molecular weight antigens. In addition, when supernatants from these cultures were assayed for IL3, further reactive antigens were detected. The results demonstrated that these approaches are useful for the identification of T cell reactive components of a complex mixture of parasite antigens in helminth infections, where the cellular nature of protection is not well defined. PMID- 2101076 TI - Preliminary results corroborating the polygenic control of immunological tolerance. AB - Tolerance-susceptible (TS) and -resistant (TR) lines of mice are in the process of bidirectional genetic selection starting from a genetically heterogeneous population achieved by the equilibrated intercrossing of eight inbred lines. Mice are intragastrically pretreated and then immunized with hen ovalbumin or bovine serum albumin and the extreme phenotypes are selected for assortative mating. The normal distribution of agglutinin titers in the F0 population and the significant interline difference already observed in the F2 and F3 generations indicate that oral tolerance is a character controlled by the additive effect of several independent loci. The mean heritability (h2) obtained thus far is 11% for the TS line and 19% for the TR line. PMID- 2101077 TI - Development of a species-specific ELISA for Brazilian pit-viper venoms. AB - Antigenic cross-reactivity between venoms of the genus Bothrops has been shown to be an extensive problem. However, some venom components are species-specific. In this study we have produced species-specific antivenoms against some members of the genus Bothrops. Monospecific rabbit antivenoms (IgG) were absorbed on venom affinity adsorbents. The species-specificity was tested by ELISA assays and immunoblots. The results of both assays showed complete species-specificity in some cases and highly increased species-specificity in others. These reagents can be used to determine the envenomating species in snake bite patients as an aid to improved serotherapy. PMID- 2101078 TI - Further characterization of Ascaris suum component(s) with suppressive activity on the IgE antibody response. AB - In order to characterize the component(s) of Ascaris suum responsible for damping of the IgE antibody production we demonstrated that the extract incubated in sodium acetate buffer, pH 4.5, maintained its suppressive effect and the same protein banding pattern by SDS-PAGE. Elimination of the lipoprotein components of the extract also left its damping properties unchanged. SDS-PAGE of the lipoprotein-free extract revealed practically the same pattern as shown by the whole extract, except for the high molecular weight polypeptides. These results indicate that the suppressive component(s) of A. suum did not precipitate and retained their activity at low pH. In addition, they appear not to be lipoproteins. PMID- 2101079 TI - Role of platelets in the in vivo removal of T. cruzi from circulation. AB - The possible role of platelets in the clearance of Trypanosoma cruzi was studied in vivo in A/sn female mice. Platelet depletion achieved by anti-platelet IgG antibodies induced a significant, though not total, reduction in the rate of removal of T. cruzi bloodstream trypomastigotes (BTRYS) from the circulation. Furthermore, during removal of T. cruzi BTRYS from the circulation of normal mice there was a simultaneous decrease in the number of platelets. These results suggest that platelets play a role in the in vivo mechanism of defense against T. cruzi infection. PMID- 2101080 TI - The development of the retinal projection to the olivary pretectal nucleus in normal and monocularly enucleated hamsters. AB - The projection to the olivary pretectal nucleus (OPN) from the contralateral eye is observed on the first day after birth and appears adult-like on postnatal day 5. The ipsilateral projection is present at postnatal day 4, and expands to fill the nucleus overlapping the contralateral projection, though never as dense, between days 6 and 8. Then, in normal hamsters, ipsilaterally projecting fibers retract to the ventral side of the OPN by day 10. However, the dense expanded projection in the dorsal OPN ipsilateral to the remaining eye in monocularly enucleated hamsters persists into adulthood. PMID- 2101081 TI - Protective effect of short-term post-ischemic hypothermia on the gerbil brain. AB - 1. The effects of post-ischemic hypothermia were studied in the gerbil brain. After 5 min of bilateral common carotid occlusion (BCCO) under thiopental anesthesia and normothermia (rectal temperature of 37 +/- 0.5 degrees C) 20 animals were maintained either normothermic (group NT, N = 10) or hypothermic (rectal temperature of 29 +/- 0.5 degrees C, obtained within 5 min of carotid recirculation) for 5 h (group HT, N = 10). Sham-operated animals (N = 5) were kept normothermic for 5 h following the surgical procedure. 2. After a 7-day period of survival, damage to the dorsal hippocampus was determined histopathologically by cresyl-violet staining and graded on a scale of 0 to 3. The histopathological damage observed in the CA1 subfield of the hippocampus was found to be more intense in NT than in HT gerbils (P less than 0.001, Mann Whitney U-test). 3. These results suggest that moderate and short-lasting hypothermia induced early in the recirculation period protects the brain against ischemic injury. The importance of these results is discussed in terms of pathophysiology, treatment and interpretation of experimental brain ischemia data. PMID- 2101082 TI - Rostrum movements in desynchronized sleep as a prevalent manifestation of dreaming activity in Wistar rats. AB - Considering that eye movements express visual dreams in humans and are prominent during desynchronized sleep in cats, monkeys and birds, rostrum movements were investigated in a macrosmatic species, the rat, to assess the hypothesis that, expressing olfactory and tactile (involving the vibrissae) dreams, they would prevail over eye movements. Desynchronized sleep episodes lasted 148.8 +/- 12.4 s, rostrum movements lasted 80.7 +/- 6.9 s and eye movements occurred during 40.4 +/- 3.9 s, all in accordance with the original hypothesis. PMID- 2101083 TI - Drinking behavior in thyroidectomized rats: effects of central cholinergic stimulation and of water deprivation. AB - Normally hydrated thyroidectomized (TX) rats stimulated intracerebroventricularly with carbachol and dehydrated TX rats drank significantly smaller volumes of water than their respective controls. This suggests lower central sensitivity to thirst and to drinking behavior induced by both cholinergic activation and extracellular fluid depletion. Dehydrated TX rats excreted a significantly larger urinary volume than the controls, suggesting the existence of changes in the renal mechanisms of water retention. Such changes could be related to a reduction in vasopressin binding sites. PMID- 2101084 TI - Spermatogenic and steroidogenic testicular function in hypothyroid pubertal rats. AB - The reproductive system of immature rats is held to be more influenced by thyroid dysfunction than that of adult animals. The effect of hypothyroidism on the spermatogenic process of the rat has not been reported previously. The objective of the present study was to investigate the spermatogenic and steroidogenic functions of pubertal hypothyroid rats. Hypothyroidism was induced by ad libitum ingestion of a 0.05% solution of propylthiouracil for 60 days, and confirmed by reduced plasma thyroxine levels in treated rats. Plasma testosterone level, the histological features of the testis and cauda epididymis and the concentration of spermatozoa stored in the cauda epididymis were unchanged by hypothyroidism. PMID- 2101085 TI - Saturated fatty acids with different chain lengths as ketogenic substrates in the rat liver. AB - Production of ketone bodies, activation of oxygen uptake and production of [14C] carbon dioxide due to fatty acids of various chain lengths were measured in the isolated perfused rat liver. As ketogenic substrates, the fatty acids investigated can be ordered in the following sequence: stearate less than palmitate less than laureate less than decanoate less than miristate less than octanoate. For activation of oxygen consumption, the same sequence is observed. A good linear correlation between the increase in oxygen uptake (delta O2) and production of ketone bodies was found, with a mean delta O2 of 0.66 mol per mol ketone bodies. This is a relatively low value when confronted with the known stoichiometry of beta-oxidation, and may be an indication of complexities in the metabolism of exogenously added fatty acids in the perfused liver. PMID- 2101086 TI - Nickel chloride effects on erythrocyte generation of superoxide radical. AB - The superoxide anion (O2-) is an extremely potent free radical which is produced during the metabolism of aerobic living cells. (O2-) may be involved in lipid peroxidation reactions which occur in a variety of systems. Cu-Zn superoxide dismutase, a metalloprotein, catalyzes the dismutation of the superoxide free radical and protects cells against superoxide damage. The ability of NiCl2 to prevent lysis of erythrocytes was tested in rats. NiCl2 administered by intratracheal route prevented hemolysis and decreased total lipids, phospholipids and bilirubin in serum. The protective effect of NiCl2 was linked to an increase in the erythrocyte activity of superoxide dismutase. PMID- 2101087 TI - A short-term low-protein diet reduces glomerular filtration rate in insulin dependent diabetes mellitus patients. AB - 1. The effect of a 7-day low-protein diet on renal function was studied in 17 normotensive, normoalbuminuric, insulin-dependent diabetes mellitus (IDDM) patients. Glomerular filtration rate (GFR) and urinary albumin excretion (UAE) were measured after 7 days on an isocaloric low-protein diet (0.5 g protein/kg per day). 2. Compliance was confirmed by 24-h urinary urea levels. GFR was measured after a single injection of 51Cr-EDTA and UAE by radioimmunoassay. 3. GFR was reduced by 13.8% on the low-protein diet (139.9 +/- 27.7 vs 120.4 +/- 25.1 ml min-1 (1.73 m2)-1) (P less than 0.05). This effect was of the same magnitude as that obtained by others after long-term strict metabolic control. No changes were observed in UAE (5.6 +/- 6.4 vs 5.7 +/- 6.8 micrograms/min) during the study. The patients were classified as hyperfiltering (N = 9; GFR = 160.3 +/- 16.6 ml min-1 (1.73 m2)-1) or normofiltering (N = 8; GFR = 117.1 +/- 17.6 ml min 1 (1.73 m2)-1) on the basis of GFR, and no difference in the reduction of GFR was observed in either group. 4. The reduction in GFR is probably caused primarily by the reduction of protein intake since other factors that might influence the GFR such as glucose control and blood pressure did not change during the study. PMID- 2101088 TI - Differences in first-phase insulin release between normal blacks and whites. AB - This study was designed to compare insulin release during the intravenous glucose tolerance test (GTT) in normal blacks and whites. The study included 14 normal blacks (9 males and 5 females) and 15 normal whites (10 males and 5 females). The index of first phase insulin release (sum of 1 + 3 min insulin levels and total area under the curve for the first 10 min of the GTT) was significantly higher in blacks. The difference is discussed in terms of genetic and acquired traits. PMID- 2101089 TI - Interactive effects of deafferentation and target removal on cell death in the parabigeminal nucleus of developing rats. AB - This study was designed to test the effects of simultaneous deafferentation and target removal on cell death in the parabigeminal nucleus. Bilateral lesions of the superior colliculus were made in newborn rats and neuron death was evaluated in the dorsal (PBd), middle (PBm) and ventral (PBv) divisions of the nucleus. When the results of the bilateral lesions were compared with the effects of unilateral lesions reported in a previous study simultaneous deafferentation and target removal were found to produce an increase in the rate of cell death greater than, and with a time course differing from that, predicted by the sum of the separate effects of removal of afferents or targets. These data suggest that the trophic effects of afferents and targets interact during the period of naturally occurring cell death. PMID- 2101090 TI - Development of abnormal lamination and binocular segregation of retinal afferents onto the rat superior colliculus. AB - Unilateral optic tract lesions made in newborn rats produce abnormal retinotectal pathways on the opposite side. The present investigation was designed to study the development of the abnormal retinal projections in the superior colliculus using anatomical tracing methods. The aberrant uncrossed retinotectal pathway develops within the first postnatal week. In spite of this, the retraction of the crossed projection, which indicates binocular segregation, is of late onset. This indicates that the induced segregation of retinal inputs is not dependent on regressive events such as ganglion cell death and terminal field retraction. These data and the results of lid-suture experiments are consistent with a role for spontaneous retinal activity in the regulation of the plasticity of retinal projections to the rat superior colliculus. PMID- 2101092 TI - Development of interhemispheric connections through the anterior commissure in hamsters. AB - The development of interhemispheric connections through the anterior commissure was studied in hamsters by use of the postmortem fluorescent tracer diI. Labelled commissural axons were seen to approach midline and cross it on E14 (E1, day of conception), extend into the opposite hemisphere and reach the terminal targets on E15, and start to arborize on E16. On P1 (day of birth), a few labelled neurons could already be seen in the anterior olfactory nucleus, olfactory tubercle, piriform and insular cortices, nucleus of the lateral olfactory tract, bed nucleus of the stria terminalis, amygdaloid complex, temporal, perirhinal and entorhinal cortices. In all these regions, labelled neurons became progressively more numerous on P3, P5 and P10, but their distribution did not change. Since no evidence of topographical exuberance of connections could be found, it is hypothesized that the development of anterior commissure connections is entirely progressive, lacking the regressive events that characterize callosal ontogenesis. PMID- 2101091 TI - Liver and kidney nitrogen uptake in rats fed beans enriched with 15nitrogen through (15NH4)2SO4 used as soil fertilizer. AB - This study was conducted to determine the incorporation of 15nitrogen (15N) into liver and kidney of a group of rats (N = 17) fed a mixture of cooked rice and beans for 4 weeks. The beans (Phaseolus vulgaris), grown in soil cultivated with (15NH4)2SO4, had 1.5% 15N enrichment. Three or four rats were sacrificed weekly and a control group (N = 13) received an isonitrogen and isocaloric reference casein diet. The amount of nitrogen transferred from the beans to the liver at the end of the first, second, third and fourth weeks was 17, 11, 27 and 29% of the total nitrogen, respectively. For the kidney, the respective values were 10, 9, 25 and 27% of the total nitrogen. The total nitrogen content of the liver and kidney of rats receiving the reference casein control diet was similar to that of the rice/beans animals. Weight gain was similar for the two groups, indicating the well-balanced biological value of the experimental diet. The present study shows that it is possible to monitor 15N incorporation into beans and subsequently into rat liver and kidney, in contrast to classical methods for protein metabolism evaluation which measure only total body nitrogen intake and excretion or weight gain. PMID- 2101093 TI - Anxiolytic effect of kynurenic acid microinjected into the dorsal periaqueductal gray matter of rats placed in the elevated plus-maze test. AB - The effect of kynurenic acid (20 to 160 nmol) microinjected into the dorsal periaqueductal gray matter was measured in rats placed in an elevated plus-maze. Microinjection of 160 nmol of kynurenic acid increased the percentages of open arm entries and of time spent in the open arms. Both of these measures may be considered indexes of anxiolysis. Although kynurenic acid also increased the total number of entries, analysis of covariance shows that the increase in open arm entries is independent of the effect on closed arm entries. Thus, the anxiolytic effect of kynurenic acid detected in the elevated plus-maze strengthens the proposal that glutamatergic neurons of the dorsal periaqueductal gray matter play an important role in anxiety. PMID- 2101094 TI - Learning impairment in chronic epileptic rats following pilocarpine-induced status epilepticus. AB - Male Wistar rats were subjected to pilocarpine-induced status epilepticus and allowed to recover. After reaching the chronic state with spontaneous seizures they were tested in an 8-arm radial maze. During learning trials, epileptic rats made significantly more errors than controls. Even in the last trials epileptic rats did not improve their performance, indicating severe learning disability. These results suggest that spontaneous seizures after pilocarpine-induced status epilepticus are a useful model for studying the learning and memory impairment detected in some cases of symptomatic epilepsy. PMID- 2101095 TI - Seropositivity to Chlamydia trachomatis in prostitutes: relationship to other sexually transmitted diseases (STDs). AB - The prevalence of Chlamydia trachomatis and its relationship with other sexually transmitted diseases (STDs) was investigated by serological determinations in a group of 45 women working as prostitutes in Santos, State of Sao Paulo. Seropositivity to HIV-1 was demonstrated in 4 (9%) of the cases and to HIV-2 in one case. Syphilis and hepatitis B were detected in 29% and 43% of the 45 women, respectively. Specific antibodies to C. trachomatis were found in all subjects. The high seroprevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), syphilis and C. trachomatis in this population was related to predisposing factors such as number of sexual contacts, sexual practices, drug use and episodes of sexually transmitted diseases (STDs). PMID- 2101096 TI - Indomethacin affects the development of tolerance to ethanol-induced diuresis. AB - The present study analyzes the effect of indomethacin on the development of tolerance to the diuretic effect of ethanol. Male Wistar rats were treated with ethanol (2 g kg-1 day-1, ip) over a period of 4 weeks and the effect of ethanol on diuresis was assessed weekly. A significant tolerance to the diuretic effect of ethanol was detected after 3 weeks of treatment. However, rats treated simultaneously with ethanol plus indomethacin (5 mg/kg, ip, on alternate days) showed no tolerance to ethanol even after 4 weeks of treatment. The fact that indomethacin prevented the development of tolerance to the diuretic effect of ethanol but had no influence on diuresis per se suggests that prostaglandins play a significant role in the mechanisms of tolerance to ethanol. PMID- 2101097 TI - Microinjection of D-2-amino-7-phosphonoheptanoate into the dorsal periaqueductal gray matter reduces the pressor response to glutamate injected at the same site. AB - The current study assesses the influence of the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-7-phosphonoheptanoate (AP7) on the pressor effect of glutamate microinjected into the dorsal periaqueductal gray matter (DPAG) of urethane-anesthetized rats. Glutamate (20, 40 and 80 nmol/site) caused dose related reproducible increases in systolic and diastolic blood pressure. Microinjection of saline into the DPAG did not alter the pressor effects of glutamate (80 nmol/site). Similar pretreatment with AP7 (2 nmol/site) significantly (P less than 0.05) attenuated the pressor effects of glutamate from +26.5 +/- 7.0 to +3.4 +/- 3.3 mmHg (systolic blood pressure). We conclude that the pressor effect of glutamate in the DPAG is mediated largely by activation of NMDA receptors. PMID- 2101098 TI - The effect of phentolamine on the pressor response to centrally administered clonidine in rats. AB - In the present study we investigate the effect of the previous injection of phentolamine (a nonspecific alpha-adrenergic antagonist) into the lateral hypothalamus (LH) and lateral ventricle (LV) on the pressor and bradycardic responses produced by the injection of clonidine (an alpha 2-adrenergic agonist) into these same areas of conscious rats. The injection of clonidine into the LV and LH produced pressor (39 +/- 5 and 38 +/- 3 mmHg, respectively) and bradycardic responses (-65 +/- 16 and -94 +/- 13 bpm, respectively). Previous injection of phentolamine into the LH or LV reduced the pressor response to clonidine injected into the same areas (delta MAP = 13 +/- 6 mmHg for LH and 1 +/ 3 mmHg for LV). No reduction was observed when clonidine was injected into the LV after the injection of phentolamine into the LH. No changes in bradycardic responses were observed after treatment with phentolamine. The present results show the participation of alpha-adrenergic receptors in the pressor response to centrally administered clonidine but not in the bradycardic response. The data also suggest that the pressor effect produced by the injection of clonidine into the LH is due to the activation of alpha-adrenergic receptors located specifically in this area. The pressor response after injection of clonidine into the LV and of phentolamine into the LH is due to the action of clonidine on other cerebral areas. PMID- 2101099 TI - Effect of maternal exercise during pregnancy on maternal body components and fetal growth in young and adult rats. AB - In order to investigate the effects of exercise training on maternal adiposity and fetal development, young Wistar rats (45-50 days old) were divided into four groups: control non-pregnant, control pregnant, exercise-trained non-pregnant and exercise-trained pregnant. Four equivalent groups of adult rats (90-100 days old) were also used. Trained rats swam 1 h/day, 5 day/week throughout pregnancy or for a 22-day period (non-pregnant rats). Physical activity during the entire gestational period reduced weight gain during pregnancy. Both control and trained pregnant rats showed an increase in food intake during the 2nd week of pregnancy and increased food efficiency. Exercise training reduced perirenal fat weight in young and adult pregnant rats. Muscle protein content, litter size and birth weight of pups were similar for control and trained rats. These results indicate that the energy expenditure required during exercise training by both young and adult pregnant rats reduces depot fat and does not seem to alter normal gestation. Counterregulatory mechanisms during pregnancy and exercise training result in increased food efficiency which probably preserves both maternal and pup metabolism. PMID- 2101100 TI - Disruptive effect of the mesencephalic reticular formation on tonic immobility in guinea pigs. AB - Cholinergic stimulation of the mesencephalic reticular formation with carbachol impairs the induction of tonic immobility (TI) by restraining maneuvers and reduces the duration of immobility episodes in guinea pigs. This finding apparently disagrees with the hypothesis that environmental monitoring occurs during TI which permits the animal to evaluate the best time for escape. It is possible that this monitoring involves circuits and neurotransmitters other than the ascending cholinergic system originating in the mesencephalic reticular formation. PMID- 2101101 TI - Energy balance of pregnant rats. AB - Energy balance of pregnant and non-pregnant female rats was determined after 20 days of gestation. Energy contents of male and female pups and placentae were also determined. The metabolizable energy intake of pregnant rats was 33% higher than that of non-pregnant controls. Body weight gain was 9.4-fold that of non pregnant rats. Gains in energy and body weight in pregnant rats exceeded those of pups and placentae. This implies that the excess energy was stored, probably for later use in an energy-requiring process such as lactation. Food was processed as expected in pregnant rats, since although gross food efficiency (gain in body energy divided by metabolizable energy intake) was greater in pregnant than in non-pregnant rats (5.4% vs 17.5%), only 53.7% of the extra energy intake was deposited in the dams. PMID- 2101102 TI - Activation of the Langendorff perfused rat heart under depolarizing conditions. AB - Myocardial activation under depolarized conditions was studied in spontaneously beating Langendorff perfused hearts from albino rats. Depolarization was obtained increasing external potassium concentration in steps (5.4, 7.4, 10, 10.5, 11, 11.5 mM) in the perfusing solution. Left ventricular isovolumic systolic pressure and coronary flow did not change as external potassium increased, but the atrial and ventricular beat rates decreased, the latter showing a larger decline. In the electrocardiogram, the P-R interval increased as a function of external potassium and the amplitude of the QRS complex diminished as its duration increased. The majority of perfused hearts stopped pumping when external potassium was raised to 11.5 mM. PMID- 2101103 TI - Ionic dependence of cell volume regulation by the thin ascending limb of Henle's loop. AB - Thin ascending limb cells from Henle's loop were studied with optical and video techniques to evaluate cell volume regulation in response to anisoosmotic media and its ionic dependence. Cell volume regulation was observed when these cells were exposed to hypoosmotic solutions. Under hyperosmotic conditions only an osmometric response was found, with no volume regulatory increase (VRI). The removal of Cl- or HCO3- abolished the volume regulatory decrease (VRD) normally observed during exposure to hypoosmotic solutions. Re-addition of these ions did not elicit the VRD response. The removal of K+ from hypoosmotic solutions abolished VRD but its re-introduction restored the volume regulatory response. In the absence of Na+, a partial inhibition of VRD was found; re-addition of Na+ completely restored the regulatory response. These indicate that cells from the thin ascending limb of Henle's loop regulate their volume under hypoosmotic conditions, and that this process is dependent upon Cl-, HCO3-, Na+ and K+, with different patterns of response being observed upon addition or deletion of these ions. PMID- 2101104 TI - Survival of retinal ganglion cells in vitro: the effect of conditioned medium from retinal cell aggregates. AB - The time course of degeneration of retinal ganglion cells was studied in vitro. We used the retinae of newborn hooded rats retrogradely labeled with horseradish peroxidase injected bilaterally into the superior colliculus to permit the identification of retinal ganglion cells in culture. We tested the effect of conditioned medium either from aggregates or from explants of retinal cells on the survival of the ganglion cells. Both conditioned media approximately doubled the survival of ganglion cells after 48-72 h in culture. Our data are consistent with the hypothesis that retinal cells produce soluble trophic factors that influence ganglion cell survival. PMID- 2101105 TI - Thyroidectomy reduces stress-induced prolactin secretion in rats. Participation of brain serotonergic systems. AB - Plasma prolactin levels were measured in thyroidectomized and sham-operated rats under immobilization stress. Thyroidectomy significantly reduced prolactin secretion during stress. The pretreatment of thyroidectomized rats with 6-chloro 2-[1-piperazinyl]- pyrazine (MK 212), a serotonin agonist that easily penetrates the blood-brain barrier, reversed the reduction in stress-induced prolactin release in the thyroidectomized group. PMID- 2101106 TI - Inhibition of renal electrolyte excretion by gabaergic pathways of the lateral hypothalamic area. AB - Injection of gamma amino butyric acid (GABA) into the lateral hypothalamic area of unrestrained conscious rats caused a decrease in renal electrolyte excretion with an increase in urinary flow. When picrotoxin, a specific inhibitor of gabaergic pathways, was administered, a significant increase in renal water and electrolyte excretion occurred. The effect of simultaneous injection of picrotoxin and GABA into the same site indicated that picrotoxin was less potent in reversing the effect induced by GABA than GABA was in reversing the effect of picrotoxin. We conclude that GABA acts directly on the neuronal mechanisms involved in the control of water and electrolyte excretion, perhaps by exerting a tonic inhibitory action on renal electrolyte excretion. PMID- 2101107 TI - Richardson Cross lecture 1989 amblyopia--an historical perspective. PMID- 2101108 TI - Risk factors in amblyopia. AB - Any intervention to prevent serious amblyopia is based on the knowledge about normal versus subnormal visual development. Our ability to predict with high degree of certainty which children will develop amblyopia will be dependent on the characteristics of various risk factors for initiating the development of squint or amblyopia. We have used longitudinal studies of population based cohorts of young children to define some of these risk factors such as refractive errors. Three hundred and ten children with an astigmatism greater than or equal to 1.0 D at one year of age were refracted yearly between the age one and four years. Astigmatism and anisometropia were found to be highly variable during infancy and early childhood. Longitudinal follow-up seems to be needed to separate the normal from the abnormal refraction development, which initiates the development of the amblyopia. Children with constant or increasing astigmatism or anisometropia between one and four years were 'at risk'. In parallel we have studied important factors for successful treatment of amblyopia. Based on these findings we conclude that a population screening at four years of age seems to be advantageous in Sweden in order detect and successfully treat most cases of amblyopia. PMID- 2101109 TI - A perspective on psychophysical testing in children. AB - In this paper, we show that the development of acuity in infancy is not due solely to foveal maturation, since there is a clear development of acuity in the peripheral visual field. The development of peripheral acuity, and the naso temporal asymmetry during early development reinforce the idea that the visual loss in adult strabismic amblyopes is not due to an arrest of development, but rather to the chronic interocular suppression of the deviated eye. The Teller Acuity Card Test does not reliably detect strabismic amblyopia, and therefore should not be recommended as a screening test. However, the test is adequate for diagnosing visual losses in children with organic eye disorders and possibly anisometropia. PMID- 2101110 TI - White light interferometry in amblyopic children--a pilot study. AB - Interferometric acuity using the IRAS white light interferometer was compared with Snellen acuity in nine amblyopic children between the ages of five and nine years, and nine aged matched controls. All of the amblyopic eyes achieved better grating acuities than Snellen acuities. Fifty-seven per cent of the amblyopes with a best corrected Snellen acuity of 6/18 or less in their amblyopic eye, achieved grating acuities indistinguishable from normal. The hand held white light interferometer may have a role in the assessment of meridional amblyopia and in children with high astigmatic errors. PMID- 2101111 TI - The influence of dopamine on spatial vision. AB - Contrast thresholds for, and contrast matches between, stationary gratings of three spatial frequencies (0.5, 2, and 8 c/deg) were measured on eight subjects with a history of schizophrenia, just before, and again two to three days after, a therapeutic injection of depot neuroleptic. The drug enhanced sensitivity at the low, and reduced it at the medium and high spatial frequency. After injection, subjects required more contrast to match the apparent contrast of the high, and less contrast to match that of the low, to that of the medium spatial frequency. Pupillary measurements suggested that these effects were not due to drug-induced changes in pupil size. The results are discussed in terms of the functional role of dopamine in the retina, and a possible application in therapy for amblyopia. PMID- 2101112 TI - Second eye involvement in age-related macular degeneration: a four-year prospective study. AB - Age-related macular degeneration (AMD) usually affects both eyes over time. Among patients with advanced AMD in one eye estimates of the risk to the second eye have been diversely reported. Therefore we examined, over a four year period, the rate of second eye involvement in 41 patients with either exudative or advanced atrophic AMD in one eye, and early macular changes in the second eye with best corrected vision of 20/30 or better. The cumulative risk of developing either exudative AMD or atrophic AMD and 20/80 or less vision in the second eye was 23% at four years. The cumulative risk of losing 10 or more letters on the ETDRS visual acuity chart in the second eye was 35% at four years. These results are discussed in relation to previously reported rates of second eye involvement in AMD. PMID- 2101113 TI - Filtering surgery with 5-fluorouracil: a second course. AB - In five glaucoma patients, a previous filtering surgery that was followed by sub conjunctival injections of 5-Fluorouracil (5-FU) failed, due to filtering bleb scarring. A repetition of the filtering surgery with subsequent sub-conjunctival injections of 5 mg of 5-FU, administered once daily for 8-14 days, was undertaken. At the end of 6-19 months of follow-up, IOP levels in all five eyes were 20 mmHg or less with medication. A repeated course of filtering surgery plus 5-FU treatment seems to be a favourable surgical option in refractory glaucoma. PMID- 2101114 TI - The effect of Nd:YAG iridotomy on intraocular pressure in hypertensive eyes with shallow anterior chambers. AB - Eighty one eyes of 48 patients with raised IOP and shallow anterior chambers underwent Nd:YAG iridotomy to prevent further angle closure glaucoma and to remove any pupil block that might be contributing to the raised IOP. These eyes were followed for 18-34 months to assess the effect on IOP control. Seventy three eyes of 43 patients were asymptomatic. In eyes with no PAS none responded with drop in IOP but in eyes with well established PAS 69% showed a drop in IOP. By comparison eight eyes of five patients had a history of episodes of subacute angle closure glaucoma. All had PAS present pre-operatively. Iridotomy reduced IOP in 87.5% of the eyes in this group and rendered 100% symptom free. Permanent posterior synechiae between lens and iris were an invariable complication in those eyes that required long-term miotic treatment for IOP control following iridotomy. In asymptomatic eyes with chronic pressure elevation and narrow angles laser iridotomy is unlikely significantly to reduce the IOP. We recommend that in such eyes iridotomy should be reserved for those eyes with established closure of the angle by PAS in which IOP control can be achieved without the use of miotics. PMID- 2101115 TI - Stress birefringence in the human cornea. AB - Stress-induced birefringence is used in engineering to determine the distribution of mechanical stress in experimental models. The phenomenon has previously been reported in the cat cornea but no data for the human exists. A qualitative description of stress-induced birefringence in the human cornea in vitro is presented. Circularly polarised light is then used to detect the phenomenon in the post-operative human cornea in vivo. PMID- 2101116 TI - Acanthamoeba keratitis--resistance to medical therapy. AB - Successful medical therapy of Acanthamoeba keratitis has been reported with combination therapy; topical Brolene and neomycin. Resistance has not so far been identified as a problem, but was the basis for recurrent disease observed in a patient with bilateral infection. Eradication of amoebae was finally achieved following prolonged topical therapy and two corneal grafts in each eye. Topical anti-amoebic therapy with paromomycin, benzethonium chloride, clotrimazole and R11/29 (a phenanthridinium compound), was continued for three months post operatively. No further recurrences occurred during 14 months' follow-up. Drug sensitivities were performed for three isolates of Acanthamoeba sp (group II) which demonstrated the development of resistance to Brolene and arsenic. In addition, the resistant isolates were temperature-sensitive mutants which would not grow at temperatures above 30 degrees C. This could explain 'culture negative' results in some cases of clinical recurrence when incubation of laboratory samples had only been performed at 37 degrees C. PMID- 2101117 TI - Ophthalmological significance of HLA associated uveitis. AB - The association between HLA-A29 and birdshot chorioretinopathy is the strongest association between HLA and disease ever described. The determination of HLA-A29 is therefore of diagnostic significance. The association between HLA-B27 and acute anterior uveitis (AAU) is much weaker. However, it is evident that B27+ AAU is clinically different from B27-AAU. Half of the B27+AAU patients have or will have ankylosing spondylitis or Reiter's syndrome. The determination of HLA-B27 is therefore of clinical significance and should be determined in each case of AAU. The B27+ patients should be referred to a rheumatologist. The determination of HLA-Bw51 is of limited but significant diagnostic value for the diagnosis of Behcet's disease in countries around the Mediterranean Sea or Japan. In Northern Europe HLA-Bw51 determination will not give much practical information. The structure and function of HLA class I molecules is now known. It is probable that HLA-A29 and HLA-B27 molecules are directly involved in the pathogenesis of respectively birdshot chorioretinopathy and AAU. PMID- 2101118 TI - Ophthalmic complications of amniocentesis. AB - Reports of ocular damage from amniocentesis needles are rare. We report four cases of ocular perforation in which an amniocentesis needle may have been the cause and a proven case of central nervous system perforation during amniocentesis which resulted in hemianopia and gaze palsy. Ocular damage during amniocentesis may be commoner than the paucity of reports would suggest, and should be considered in all cases of congenital ocular conditions. PMID- 2101119 TI - Extended criteria for vitrectomy and fluid/silicone oil exchange. AB - The results of vitrectomy combined with fluid/silicone oil exchange at six months after surgery in 39 eyes with complex retinal detachments without (initially) severe proliferative vitreoretinopathy, proliferative diabetic retinopathy or giant retinal tears, are reported. Eyes with detachments as a result of macular holes, large multiple or posterior breaks, and eyes which had undergone previous, unsuccessful vitreoretinal surgery are included. In 90% the retina remained reattached, with functional improvement in 72%. These findings, together with the relatively low incidence of complications observed, lead us to recommend this technique in the management of selected detachments falling outside the parameters within which its use is generally accepted. PMID- 2101120 TI - Ocular trauma caused by air-gun pellets: a ten year survey. AB - Forty-one consecutive cases of ocular injury related to air gun pellets occurring over a ten year period have been reviewed retrospectively. The male to female ratio was 7:1 and the average age was fifteen years. Hyphaema was the most common injury (78%) while the main cause of poor final visual outcome was retinal detachment. Thirty-eight percent of the involved eyes had a final corrected visual acuity of less than 6/60 including four eyes (10%) which were enucleated following severe perforating injuries. Neither sympathetic ophthalmitis nor lead poisoning was detected in this study. The fact that these injuries are largely of an accidental nature, predominantly involve young people and appear to be occurring more frequently suggests that present legislation does not offer adequate protection. The authors suggest that the best method of prevention is through a public education campaign aimed at children and their parents. PMID- 2101121 TI - Immunoglobulin G subclass deficiency in children with high levels of immunoglobulin E and infection proneness. AB - Of 32 unrelated children with serum IgE greater than 1,000 U/ml, 17 were found to have infection proneness according to standard clinical criteria, and 15 were not infection prone. There were no statistical differences between these 2 groups of children with regard to age, sex, serum IgE levels or prevalence of asthma. However, the prevalence of eczema was significantly lower in the infection-prone group (p = 0.035). Of greater interest was the finding that 7 children in the infection-prone group had IgG subclass and/or IgA deficiency compared with none in the non-infection-prone group (p = 0.006). These results suggest that IgG subclass studies may be warranted in children with markedly elevated levels of serum IgE and proneness to infection. PMID- 2101122 TI - Determination of cow milk formula allergenicity in the rat model by in vitro mast cell triggering and in vivo IgE induction. AB - The allergenicity of cow milk formulas was assessed in vitro by their ability to trigger prelabelled 3H-serotonin release from normal rat mast cells sensitized passively with rat reaginic anti-cow milk protein antisera. It was found that enzymatically hydrolyzed milk formulas had 1,000 (BEBAHA) to over 100,000 (ALFARE) times lower mast cell-triggering capacities than a standard milk formula (NAN). In vivo, these hydrolyzed formulas induced 100 (BEBAHA) to 10,000 (ALFARE) times less IgE antibodies than the standard milk formula. PMID- 2101123 TI - Effect of locally administered heparins on delayed-type hypersensitivity reactions. AB - Inflammatory reactions involved in delayed-type hypersensitivity (DTH) are associated with extravascular coagulation and fibrin deposition. Heparin and other anticoagulants administered systemically inhibit DTH reactions but the direct effect of intradermally injected heparin on the development of DTH skin responses has not been reported. The effects of heparin on the DTH reaction elicited by ovalbumin (OVA) in guinea pigs 1-3 weeks after sensitization were examined. Unfractionated heparin, low affinity heparin (LAH; non-anticoagulant) and high affinity heparin (HAH; anticoagulant) were injected together with suboptimal amounts of OVA. Heparin and LAH enhanced skin induration, LAH (0.5 micrograms) by an average of 50% above that due to OVA alone at 24 h (p less than 0.01). In contrast, HAH (0.5 micrograms) significantly reduced skin induration at 24 h. Heparin and LAH also significantly increased cellular infiltration with LAH having the greater effect. At 4 h the infiltrate consisted mainly of neutrophils whereas at 24 h mononuclear cells predominated. Fibrin deposition, assessed both by immunohistology and quantitation of radioactive fibrin extracted from skin test sites, was increased by 30% when OVA was tested in the presence of LAH. Mast cell heparin released locally at sites of DTH has the potential to modulate these reactions in either a pro- or anti-inflammatory manner. This study is the first to demonstrate differences in the capacities of LAH and HAH to modulate cell mediated inflammation. PMID- 2101124 TI - Role of mucosal mast cells in intestinal graft-versus-host reaction in the mouse. AB - Hyperplasia of mucosal mast cells (MMC) is found in many enteropathies which are caused by T lymphocytes, but their exact role is unknown. In this study we have investigated whether MMC play a part in the immunologically mediated enteropathy which occurs in mice with graft-versus-host reaction (GvHR). There were simultaneous increases in the numbers of jejunal MMC and in the concentrations of mouse intestinal mast cell proteinase both in serum and in the intestine in two separate models of GvHR. Although these changes developed in parallel with the evolving GvHR, there was no correlation between the degree of MMC activation and the severity of the intestinal pathology. In addition, mast cell deficient W/Wv mice developed systemic and intestinal GvHR as severe as their normal congenic littermates, despite a markedly deficient MMC response. We conclude that the role of MMC in enteropathy may be to regulate or repair T lymphocyte mediated immunopathology. PMID- 2101125 TI - Immunodetection methods for grass pollen allergens on western blots. AB - A comparison is made of eight different methods to detect allergenic proteins in Western blots of rye-grass pollen extracts. Horseradish peroxidase-based enhanced chemiluminescence (ECL) provides a sensitive method for the detection of allergenic proteins. The method has been modified to use more dilute solutions of ECL substrate to reduce the background, can be applied to a standard nitrocellulose membrane, and used with Kodak X-ray film. The assays can be performed rapidly, replacing use of radiolabelled probes. Increased resolution is obtained. This makes the method suitable for detection of cDNA clones on plaque lifts, and for rapid and specific purification of proteins following immunodetection on nitrocellulose membranes. PMID- 2101126 TI - Two-dimensional gel electrophoretic analyses of Kentucky bluegrass and rye grass pollen allergens. Detection with a murine monoclonal anti-Poa p I antibody and amino terminal amino acid sequence of Poa p I allergen. AB - Allergenic extracts of Kentucky bluegrass (Poa pratensis) and rye grass (Lolium perenne) pollen were shown by 2-dimensional (2-D) gel electrophoresis to consist of several hundred protein components. The pollen extracts of the two related grasses had unique 2-D gel patterns. Two major grass pollen allergens, Poa p I and Lol p I, and their isoforms (i.e. isoallergens) were detected and localized on 2-D gels by immunoblotting with anti-Poa p I antibody mAb 60. Poa p I isoallergens were less acidic than Lol p I isoallergens. The relative proportion of four Poa p I isoallergens was (in decreasing pI): A, 13%; B, 37%; and D, 15%. The amino terminal amino acid sequences of the two major isoallergens of Poa p I were identical. However, the amino acid composition of these isoallergens showed enough differences to account for their charge differences. The amino terminal amino acid sequence of two major Poa p I isoallergens had a 70% homology in 20 amino acid overlap with the previously published amino terminal amino acid sequence of rye grass pollen allergen R-7. PMID- 2101129 TI - Toward the 14th World Congress: the religious significance of meeting. PMID- 2101128 TI - Hepatitis B--the facts. PMID- 2101127 TI - Purification and N-terminal amino acid sequence of two birch pollen isoallergens (Bet v I and Bet v II). AB - The major allergen of birch pollen BV45 (Bet v I) was previously isolated by molecular weight exclusion chromatography and eluted in the molecular weight region of 15-29 KD. Further purification of this fraction on an SP-Trisacryl M cation exchange matrix allowed 6 peaks of which which the 4th (BV4A4) and 6th (BV4A6) included two dominant IgE-binding birch pollen isoallergens designated Bet v I and Bet v II. Final purification, using the 'Applied Biosystems' Peptide Micro Separation System, revealed two sharp peaks with a high degree of homogeneity. This was ascertained by automatic N-terminal amino acid (AA) sequence analyses which showed high average repetitive yields of the phenyl thiohydantoin (PTH) AAs of the isoallergens sequenced. N-terminal AA analyses of the two fractions allowed 51 cleavages with correct identifications of PTH AAs for 3 replicates. The sequence data of the two isoallergens showed large homologies with the hazel pollen allergen, Cor a I, the birch pollen allergen, Ag 23, and the translated cDNA sequence derived from cloning birch pollen allergen genes. The sequence homologies support that Betula verrucosa allergens were derived from a gene family expressing several isologous allergens, 2 of which with 13 variable residues in a segment of 51 AAs. The antigenicity of the two fractions, Bet v I and Bet v II, was demonstrated by fused rocket immunoelectrophoresis (FRIE) and by crossed immunoelectrophoresis (CIE) giving single symmetrical antigenic precipitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101130 TI - Health care--let's look again. PMID- 2101131 TI - Care of the elderly today. PMID- 2101132 TI - Immunohistochemical detection of c-myc oncoprotein in paraffin embedded tissues. AB - In almost all studies using paraffin embedded tissue, c-myc protein has been found in the cytoplasm of cells. Since the protein is normally localized in the nucleus it is difficult to determine which histochemical observations are real and which are artefactual. The study designed here evaluated several different methods of fixation prior to paraffin embedding in an attempt to identify which would prevent the diffuse of the protein out of the nucleus. Using various fixation procedures (formalin, paraformaldehyde, B-5, Zamboni and AMeX) we found that fixation in cold acetone (-20 degrees C) overnight followed by 2x15 min fixation in acetone at +4 degrees c and at room temperature, cleared in methyl benzoate and xylene (AMeX procedure) gives reproducible nuclear staining when a variety of normal and tumor tissues are treated with an anti c-myc protein antibody. This method was then compared to frozen sections. While there was no cytoplasmic staining in same tissue specimens in both AMeX processed and frozen sections, the tissue architecture was much better preserved in AMeX processed samples. Our data strongly suggest that AMeX fixation, originally developed for T and B lymphocyte antigens, should be used for immunolocalization of c-myc oncoprotein in paraffin embedded tissues. PMID- 2101133 TI - Immunohistochemical demonstration of a thiamine diphosphate-binding protein in the brain of the adult rat. AB - We recently purified a new thiamine diphosphate-binding protein (ThDP-BP) prepared from rat liver, and found immunoreactivity for ThDP-BP in neurons and other neuronal tissues. In this study, we examined the distribution of ThDP-BP in the rat neurons by the avidin-biotin complex technique. Strong immunoreactivity for ThDP-BP was found in the cerebral cortex, hippocampus, ependymal cells, nucleus III, nucleus V, and medial vestibular nucleus. Moderate immunoreactivity was noted in the olfactorius nucleus anterior and weak activity in the nucleus ruber. ThDP-BP may be useful in clarifying the pathogenesis of Wernicke encephalopathy and Leigh's disease. PMID- 2101134 TI - Tissue response to subtotal retinectomy in a rabbit model. AB - We surgically removed lenses and as much retina as accessible in one eye of six pigmented rabbits which were followed for up to four months postsurgically. Clinically, pre-RPE membranes were noted to form within the first weeks after surgery, and eyes remained hypotensive in the absence of notable inflammation. Morphologic studies demonstrated a variable response of RPE, ranging from atrophy to hypertrophy and hyperplasia. Pre-RPE membranes appeared to arise from both the RPE as well as from tags of peripheral retina and were of two morphologic types: spindle cell-collagenous membranes, and a highly cellular glial membrane. Bone formation within collagenous membranes was seen in four of six eyes studied. PMID- 2101135 TI - Lipid peroxidation and oxidation of lignoceric acid in kidneys from thioridazine treated rats. AB - We have investigated lipid peroxidation and oxidation of lignoceric acid in response to oral thioridazine administration, to better understand the effects of phenothiazines, which are one of the more commonly used therapeutic agents. Measurements at different time intervals showed that levels of lipid peroxides in rat kidney were markedly decreased after thioridazine feeding, however, the oxidation of lignoceric acid was found to be elevated immediately after the start of thioridazine treatment. These biochemical changes were noted to be associated with mitochondrial proliferation and lipid accumulation in renal epithelial cells. The observed renal biochemical and morphological changes following thioridazine feeding return to the normal levels after two weeks of withdrawal of the drug. This study suggests that phenothiazines could be beneficial in reducing cellular injury by reducing the levels of lipid peroxides during pathological conditions like ischemia. PMID- 2101136 TI - Growth and spread of causative agent of Creutzfeldt-Jakob disease in intraperitoneally infected mice. AB - The progression of Creutzfeldt-Jakob disease (CJD) was studied in ddY mice infected intraperitoneally with the Fukuoka-1 strain, a transmissible agent isolated from a CJD patient in Japan. Infectivity became detectable simultaneously in the brain, the spleen and the liver, i.e. 19 weeks after inoculation. Infectivity titer ranged from 10(2) to 10(3) LD50/g in all three organs up to 35 weeks, in contrast to intracerebrally infected mice in which the content of infectious CJD agent is higher in the brain than in the liver and the spleen. Cuffs appeared in the brain roughly four times in the period from 3 to 37 weeks after inoculation. The observed infectivity was discussed in relation to the appearance of cuffs in the brain. PMID- 2101137 TI - Evaluation of ELISA for detection of Giardia lamblia-specific copro-antigen employing monospecific antibodies. AB - An enzyme linked immunosorbent assay (ELISA) system, using monospecific antibodies for the detection of Giardia lamblia specific 66 kDa copro-antigen has been developed and evaluated. The assay detected the antigen in stool eluates of all the 24 microscopically confirmed cases of giardiasis and in 17 (68%) of the 25 microscopy-negative clinically suspected cases of giardiasis. None of stool eluates from 20 subjects infected with other protozoal/helminthic intestinal parasites or from 20 apparently healthy subjects had G. lamblia-specific copro antigen. The ELISA employing monospecific antibodies is a sensitive and specific tool for the diagnosis of giardiasis and is especially useful for confirming microscopy-negative suspected cases of giardiasis. PMID- 2101138 TI - Attempts to quantity Clostridium botulinum type A toxin and antitoxin in serum of two cases of infant botulism in Japan. AB - Serum samples taken from two infant botulism cases during hospitalization were titrated for botulinum toxin by both the intraperitoneal (ip) injection method and the score method in mice. By the ip method, in which death is the only parameter, such low levels of toxin as lower than 4 ip LD50/ml may not be titrated even though the surviving mice show abdominal palsy. By the score method based on the degree of abdominal palsy, such low levels of toxin as 1.1 and 0.8 ip LD50/ml were detected in specimens of one of the patient's serum. No antitoxin was demonstrated in either case of infant botulism by applying the score method. It is not known whether spontaneous recovery from infant botulism is due to the antitoxin production. PMID- 2101139 TI - Determination by a site-directed mutagenesis method of active site of thermostable direct hemolysin (TDH) produced by Vibrio parahaemolyticus. PMID- 2101141 TI - Detection of variant toxin A without hemagglutination activity of Clostridium difficile and analysis of its biochemical and biological characteristics. PMID- 2101140 TI - Characterization of Vibrio cholerae non-O1 hemagglutinin/protease. PMID- 2101142 TI - Molecular genetic analysis of a factor produced by Citrobacter freundii which immunologically cross-reacted with cholera toxin (CT) and heat-labile enterotoxin (LTh). PMID- 2101143 TI - Strong activation of complement system by lipopolysaccharides (LPS) possessing mannose homopolysaccharides. PMID- 2101144 TI - Chemical structure and biological activity of lipooligosaccharide isolated from Sphingomonas paucimobilis, a gram-negative bacterium lacking usual lipopolysaccharide. PMID- 2101145 TI - Charge heterogeneity of the heat-labile enterotoxins from human and porcine enterotoxigenic Escherichia coli. PMID- 2101146 TI - The structure and function relationships of hemorrhagic factors isolated from the venoms of Trimeresurus flavoviridis and Crotalus ruber ruber. PMID- 2101147 TI - Purification and characterization of three phospholipases A2 from the venom of Vipera aspis aspis. PMID- 2101148 TI - Cloning and nucleotide sequence determination of a heat-stable enterotoxin gene from Vibrio cholerae non-O1. PMID- 2101149 TI - Studies on Clostridium botulinum type E and C1 toxin genes. PMID- 2101150 TI - Cloning and expression of staphylococcal exfoliative toxin A gene in Escherichia coli. PMID- 2101151 TI - Mechanism of cellular membrane damage induced by melittin and mastoparan. PMID- 2101152 TI - Effects of Bordetella bronchiseptica dermonecrotic toxin on structure and function of osteoblastic clone MC3TC-E1 cells. PMID- 2101153 TI - Permeability-enhancing action of Vibrio vulnificus protease and its control system. PMID- 2101154 TI - Identification of a 65 kDa cytosolic protein which is phosphorylated in murine peritoneal macrophages in stimulation with bacterial lipopolysaccharide. PMID- 2101155 TI - Biochemical analyses of the inhibition of catecholamine release by tetanus toxin in digitonin-permeabilized chromaffin cells. PMID- 2101156 TI - Isolation of theta-toxin fragments and characterization of its effect on toxin induced hemolysis. PMID- 2101157 TI - Relationship between mouse-protecting and toxin-neutralizing activities of anti pertussis toxin monoclonal antibodies. PMID- 2101158 TI - Anti-tetanus human monoclonal antibodies. PMID- 2101159 TI - Tolerance-inducing mechanisms to lethal toxicity of LPS by synthetic lipid A analogs. PMID- 2101160 TI - Partial purification of a beta-glucan-like component as a likely candidate for the Limulus factor G stimulator in the plasma of patients with hepatic failure. PMID- 2101162 TI - Studies on the mechanisms of murine T cell activation by streptococcal pyrogenic exotoxin type A. PMID- 2101161 TI - Activation of V beta 11+ murine T cells by staphylococcal enterotoxin E in the presence of accessory cells expressing MHC class II molecules. PMID- 2101163 TI - Study of T cell activation by toxic shock syndrome toxin-1 with use of murine T cell hybridomas reactive to the toxin. PMID- 2101164 TI - [Epidemiology and prevention of respiratory allergies in children]. AB - There appears to be a belief that asthma in children is increasing. Given the fact that the morbidity of asthma has not decreased despite many advances in pharmacologic treatment, it is clear that attempting at reduce exposure should come at an early stage of life. This is best accomplished through preventive measures such as dietary prophylaxis and sufficiently aggressive measures to reduce exposure to mites. PMID- 2101165 TI - Radiological changes of the ileum in children with coeliac disease: is "intestinal adaptation" a specific radiographic sign? AB - We retrospectively reviewed the radiographic findings of 86 children with chronic diarrhoea and/or short stature. Radiographic small intestine examination showed morphologic changes characteristic for the malabsorption syndrome in 58 children with coeliac disease on a gluten-containing diet. In addition, 32 (55%) of these children showed "intestinal adaptation" or "jejunalization" (increase in the number and thickness of the folds). In the control group (28 children, cross matched) 11 (39%) presented non specific radiological changes while the others presented a normal mucosal pattern. No features of "intestinal adaptation" were noted. No significant differences between CD patients with and without "intestinal adaptation" were found in the evaluation of the nutritional status, including serum levels of albumin, iron, transferrin, ferritin and zinc, and in the results of the one-hr xylose test and 72-hr faecal fat absorption test, and anti-gliadin antibody levels (IgA and IgG). No significant correlation was noted between the duration of gluten-containing diet and the presence of "intestinal adaptation". It appears that "intestinal adaptation" lends specificity to the radiographic small intestine examination, also in paediatric practice. PMID- 2101166 TI - [Oral contraceptive and hepatic effects]. AB - The general use of synthetic estrogens like DC pointed out that near many skilled collateral effects, some others that are showing with a decrease of bile excretion (cholestasis), reversible with their administration interruption; with hepatic cells adenoma that are potentially premalignant and can transform into hepatocellular carcinoma; with vascular complications such as (most frequently in carcinomatousis) "hepatic peliosis" and "thrombosis" of suprahepatic veins (Budd Chiari's syndrome). There is no overall increase in the incidence of gallbladder disease (cholelithiasis and cholecystitis). PMID- 2101167 TI - [Changes in headache with age: symptomology and clinical features]. AB - The clinical features of 76 patients 5 to 14 years old suffering from primary headaches has been compared with those of 495 adults in the same diagnostic group. An association between migraine without aura and female sex was evident in both age groups, while an inversion of the usual M/F ratio was found in the younger group with other types of headache. Childhood headache attacks resulted to be less frequent, less severe and with a shorter duration than in adult patients. Also accompanying symptoms were less common in children than in adults. Furthermore pain was more often unilateral but less frequently pulsating in the younger group. These results point out the need for a different approach to childhood headaches. PMID- 2101168 TI - [An outbreak of legionnaires' disease in the Danish community in Rome: clinical therapeutic-epidemiologic aspects]. AB - The authors report five Danish patients affected by Legionnaire's disease observed during the 1987 spring. They focus on the epidemiological, clinical, and therapeutic aspect of the outbreak. PMID- 2101169 TI - Immunological pattern in heterozygote beta thalassemic subjects. AB - In heterozygote beta-thalassemic subjects in a higher incidence of infectious diseases and of liver diseases with progression toward chronic hepatitis has been assessed. This predisposition has been suggested as being related to some immunological defects and to an altered immunological reactivity in thalassemia trait carriers. In order to evaluate whether there is a real deficiency of some humoral and cellular parameters in healthy heterozygote beta-thalassemic subjects, 128 symptom-free volunteers have been studied: 40 were heterozygote beta thalassemia carriers and 88 were normal subjects. In both groups there was no difference in: number and percentage of total lymphocytes, gamma globulins, immunoglobulins A and M, number and percentage of CD21, CD3, CD4, CD8, number of OKla*1, CD4/CD8 rations and lymphocytes' ability to respond to phytohemagglutinin. The values of immunoglobulins G and percentages of OKla*1 were found to be higher only in heterozygote beta thalassemic subjects; however, the number of CD2 in these subjects was lower. The result of the present study seems to indicate there is not significant difference between heterozygote beta thalassemic carriers and normal subjects in the more usual humoral and cellular immunological parameters. PMID- 2101170 TI - Controlled clinical trial on a new nonsteroidal anti-inflammatory drug (NSAID) therapy for arthropathic patients. AB - Following a single-blind, randomized protocol, a study was performed on two groups of 24 patients suffering from highly painful, osteoarticular phlogistic and/or degenerative affections, in order to evaluate the effectiveness and the tolerability of a new controlled release naproxen formulation in comparison with standard naproxen. Controlled release naproxen was administered at the dosage of a 750 mg/day tablet for 10-15 days; the standard naproxen at the dosage of two 375 mg/day capsules for 10-15 days. The phlogosis and pain reduction and the functional recovery, resulted similarly sharp and statistically significant following the two treatments. Both drugs showed not only an excellent effectiveness but also an elevate systemic tolerability. The local tolerability appeared higher in the group treated with controlled-release naproxen, where the side effects incidence at gastroenteric level was 12%, vs 25% in the control group. Therefore, the new experimented drug appears of excellent effectiveness and a large safety margin; it can be thus considered as a drug of first choice in the symptomatic therapy of arthrosis and other rheumoarthropathies. PMID- 2101171 TI - [Biological effects of exposure to acrylamide]. PMID- 2101172 TI - [Use of gas chromatography for determining benzoic and sorbic acid levels in orange beverage and tomato concentrate]. AB - Conditions of simultaneous determination of benzoic and sorbic acid in orange drink and tomato concentrate by gas chromatography method were developed and tested. Preservatives were isolated by extraction of the samples with diethyl ether in acidic media, and then converted into methyl esters with thionyl chloride. Methyl esters were separated on column packed with 15% EGA coated on 80 100 mesh Chromosorb W AW DMCS. The smallest amount of preservatives detectable on chromatography column is 20 ng for benzoic acid and 16 ng for sorbic acid. The recovery rate of the method ranged from 96-97% for benzoic acid and 89-92% for sorbic acid, while the variability coefficient was from 1.7-3.5% for benzoic acid and 4.5-6% for sorbic acid. PMID- 2101173 TI - [A method of atomic absorption spectrophotometry (AAS) for analysis of cadmium and lead levels in the plant material]. AB - The conditions were evolved and checked for simultaneous determination of cadmium and lead levels in plant material using the flame technique of ASA. For decomposition of the organic substances in plant material wet mineralization was used with a mixture of nitric acid, perchloric acid and sulpuric acid in volume proportions 6:2:0.25. The levels of cadmium and lead were determined in the organic phase after extraction with n-butyl acetate of the previously produced complexes with NaDDTK. The obtained limits of cadmium and lead detectability were 0.002 and 0.02 mg/kg respectively. The recovery rate of the method ranged from 96 to 98%, while the variability index was from 2.6 to 10.2%. The correctness of the evolved analytical procedure was confirmed by determination of the content of both elements in the NBS-SRM 1571 standard (orchard leaves) and by participation in the international interlaboratory investigation of the Polish standard (dried cabbage leaves). PMID- 2101174 TI - [Effect of a differentiated additive KNO3 on the quality of Zulawski cheese. I. Nitrate changes in maturing Zulawski cheese]. AB - 18 gyle of cheese in three experimental variants were produced: O variant- control product without additive KNO3; 1 variant--with 0.01% of additive KNO3; 2 variant--with 0.02% of additive KNO3. It was found that raw and pasteurized milk was not an essential source of nitrates. During the summer and autumn cycles of production it was noted respectively: 0.0-0.8 mg NO3-/kg and 0.0-7.4 mg NO3-/kg. Content of NO3- ions in cheese starter approximated their content in raw milk. However, content of nitrates in milk after preparing depended mostly on the quantity of added saltpeter. The cheese made without saltpeter was characterized by low level of nitrates, not exceeding 4.2 mg NO3-/kg, and by vestigial presence nitrites. Whereas the cheese made with additive KNO3 included to 40 mg NO3-/kg for 0.01% of additive KNO3 and to 80 mg NO3-/kg for 0.02% of additive KNO3. It was found that the most intense reduction of nitrates in cheese (to 75%) occurred between the phase of pressing and up to the first two weeks of its ripening. After four weeks' ripening process the level of nitrates in cheese became stabilized independently of the quantity of additive KNO3. After six weeks' ripening process, that is when the cheese is sent into consumption, the level of nitrates and nitrites was quite low and did not exceed 3.0 mg NO3-/kg and 1.2 mg NO2-/kg. Manufactured cheese met the requirements of FIL/IDF while taken into consideration the content of nitrates and nitrites. PMID- 2101175 TI - [Nitrates and nitrites and the utilization of beta-carotene. II. Determining the threshold of the tolerated dose of nitrates and nitrites in the diet of rats receiving beta-carotene]. AB - The limit levels of potassium nitrate and sodium nitrite were determined in the diet of rats receiving orally beta-carotene. Two 30-day biological experiments were done on male Wistar rats standardized for vitamin A level in the liver. The animals were given semisynthetic diet, without vitamin A, containing definite amounts of potassium nitrate or sodium nitrite: 4.0; 4.5; 5.0; 5.5; 6.0% of the nitrate, and 0.5; 0.6; 0.7; 0.8; 0.9; 1.0% of the nitrite. The rats were given also orally two drops of an oil solution of beta-carotene in doses of 30 micrograms per rat daily. The limit of tolerance was established measuring beta carotene utilization according to the method of balance studies and liver function test. Diet consumption and body weight of the animals were considered as well. It was found that in this experiment the limit dose, that is the dose of nitrates and nitrites over which the rats died, was 5.0% for nitrate and 0.7% for nitrite. PMID- 2101176 TI - [Effect of exercise on vitamin A utilization by rats]. AB - The effect of exercise was studies on vitamin A utilization by rat organism. The biological experiment was done using 64 growing Wistar rats with initial vitamin A levels in the liver 380 and 790 i.u. The rats were subjected during 12 days to 30, 60 and 90 minute exercise on moving track at 20 m/min speed. The rats were exercised in groups. During the experiment they were given water and food ad libitum but without vitamin A, for controlling its intake. The measure of vitamin A utilization by rat organism after its addition to the diet was determination of its level in plasma, liver and kidneys. No evident differences were found in diet intake and body mass and in vitamin A levels in plasma and kidneys in the groups of rats differing in exercise duration. Increased duration of the exercise reduced vitamin A content in the liver, and this reduction was significant in the group subjected to exercise during 90 minutes daily. PMID- 2101177 TI - Degenerative changes, DNA synthesis and mitotic activity in rat liver following single and repeated exposure to fenarimol. AB - Degenerative changes were observed in liver of rats treated with single and repeated doses of fenarimol (250 mg/kg body weight x day). Regenerative changes i.e. increase in: DNA synthesis, hepatic DNA, mitotic activity and number of binuclear hepatocytes, were also noted. PMID- 2101178 TI - [Changes in protein fractions of milk obtained from cows with mastitis caused by Staphylococcus aureus. Preliminary studies]. AB - The effect was studied of cow udder infection with S. aureus on changes of milk proteins. The tested milk was derived from two cows of the black-white lowland breed aged 5 years in the second stage of lactation. Proteins soluble and insoluble at pH 4.6 were characterized by means of starch-urea and polyacrylamide gel electrophoresis. The solution of nitrogen compound reacting with ninhydrin and soluble at pH 4.6 was separated by gel filtration, thin-layer chromatography and high-voltage paper electrophoresis, thin-layer chromatography and high voltage paper electrophoresis. In the milk of the infected cow degradation of alpha s, beta and kappa casein, and increased content of gamma immunoglobulin. In whey proteins a rise was observed of serum albumin content and a decrease of beta lactoglobulin and alpha lactoalbumin. In the solution after precipitation of casein at pH 4.6 in the milk of the infected cow a greater number of fractions reacting with ninhydrin was found. The observed range of degradation changes in milk protein in the infected cow (S. aureus) suggests that it has a negative effect on the technological, nutritional and hygienic value of milk. PMID- 2101179 TI - [Effect of glucose and swine blood on the effectiveness of the "SK" medium]. AB - The effectiveness of the "SK" medium for growth of bacteria producing green discoloration in cured meat products was examined with the addition of various amounts of glucose (0.0%, 0.01%, 0.05%, 0.1%, 0.5% and 1.0%), pig blood (0.0%, 2.5% and 5.0%). It was found that pig blood in the medium was indispensable for growth and differentiation of the green-producing bacteria, and that its optimum concentration is 5%. The effectiveness of the medium was with addition of 0.1% glucose. PMID- 2101180 TI - [Examination of plastic food-packaging materials]. AB - The aim of the work was evaluation of the hygienic quality of plastic packaging material and its elements intended for direct contact with food products. The study carried out in the years 1986-1989 comprised 3066 samples taken from 20 provinces. A considerable number of the studied materials had no attest of the State Institute of Hygiene (19.54%). The proportion of samples with such attest accepted as unsuitable was lower than that without attest (unacceptable organoleptic features--4.83%, or results of chemical investigations--2.87%). In some materials high amounts of cadmium and lead were found which suggested that they had been made of technical plastic materials containing unacceptable stabilizers or dyes derived from these metals. The obtained results indicate the necessity of control of plastic materials intended for contact with food products to eliminate these which would have a negative effects on the health. PMID- 2101181 TI - [A method of determining trace amounts of aromatic amines in dyed cotton textiles]. AB - A method is described for determination of trace amounts of aromatic amines present as toxic contaminants in samples of dyed cotton textiles. The study was carried out on samples of cotton textiles for children, two were dyed beige and aquamarine , one was white. A distillation-spectrophotometric method was used based on the diazo reaction of sodium nitrate + with amines and coupling reaction with alpha-naphthol. The intensity of the obtained colour was proportional to amine content in the sample. The absorbance of the colour solution was measured at 570 nm wavelength. It was shown that the tested samples contained only traces of aromatic amines calculated as aniline++--0.85-3.22 mg/kg (the acceptable amount is 40 mg/kg). The proposed method makes possible objective determination of aromatic amines in textiles, it is simple and highly effective, with detectability of the order of 10(-7) g/cm3. It may be used for amine determination in industry. PMID- 2101182 TI - [Changes in psycho-physical stress in third-class high school students as a result of school reform]. AB - Before the introduction of school reform 344 students of third classes of high schools (238 girls and 106 boys) were examined, and after introduction of the reform - 373 students (240 girls and 133 boys) were examined. The psychophysical stress of the students was assessed by means of standardized inquiry containing 77 questions grouped so that it was possible to evaluate psychophysical stress connected with ++school work, home work, timing of work during the day, situation of the student in class and in family, and with the psychic state. The sum of points obtained from all questions gave information on the total psychophysical stress. Responses to certain questions defined objectively the situations of stress and subjective experiencing of their fatigue. The school reform increased the general psychophysical stress. Before and after introduction of the reform in school programmes the stress felt by girls was greater than that of boys. The introduction of changes in the programmes had a different effect on the intensity of stress in girls and boys. In girls the stress resulting from the objectively existing stressful situation, from schoolwork and timing of work during the day was greater. The stress experienced by boys was increased in the aspects of schoolwork, situation of the student in his class and family, and psychic state, as well as subjective experiencing of stresses. PMID- 2101184 TI - [Viral hepatitis in children]. PMID- 2101183 TI - [Exposure of schoolchildren and teachers to noise at school]. AB - The factor of decisive influence on the acoustic climate in rooms is the inner noise, which is dependent in schools on the activity of children, overcrowding of classes and inadequate use of technical protective means. The inappropriate location of schools, although also important from the standpoint of acoustics, is a much lower source of noise than it is generally assumed. Particularly unfavourable acoustic conditions are in elementary schools with over 300 children in one shift. The spaces with the highest noise level include corridors, especially during recesses between lessons. The noise level in them is in the range of an equivalent sound A 60-95 dB, and the most frequent noise level is 80 dB. In a large part of schools the acoustic conditions in the corridors during recesses approach the critical values accepted for hearing protection in industrial plants, in some schools they are even exceeded. The situation is also unfavourable in other rooms such as doctor's office, director's room, reading rooms, rooms for teachers. These rooms are situated usually without taking into consideration of the acoustic conditions. This is particularly true of teachers' rooms which should give the teachers the possibility of resting before the next lesson. During lessons the noise level decreases in all rooms. However, the noisiest among them, corridors, classes situated near the hall for physical exercises and day-room, have still up to about 65 dB noise level. Generally speaking, in about 60% of rooms the acoustic conditions are below the recommended standard. The main cause, apart from overcrowding of schools, is low acoustic absorption ability of school rooms, and poor acoustic insulation ability of the doors in schools. PMID- 2101185 TI - [Physiotherapeutic treatment in the recuperation of rheumatoid hands]. AB - In restoring the rheumatoid hand, the balneo-physical therapy considers the restrain of the painful and inflammatory phenomena, and the prevention and correction of the deforming lesions with the view to restore the muscle prehension. The final aim is the function restoration and the socio-professional readjustment of the patients. The author presents in detail the devices of physical therapy. PMID- 2101186 TI - [Acute bronchiolitis]. AB - The paper reports on the high incidence of bronchiolitis, and reviews the main aspects of the disease in the infants. A better way of detection, evolution follow-up and treatment in each case is thus possible. PMID- 2101187 TI - [The child and its doll]. PMID- 2101188 TI - [The moral implications in the verbal behavior of allied health personnel]. PMID- 2101189 TI - [The care of burn patients]. PMID- 2101190 TI - [Menstrual cycle disorders in young girls]. PMID- 2101191 TI - [Patient recuperation from chronic hepatitis]. PMID- 2101192 TI - [Scientific terms in pathology in the first Romanian printings of medical interest]. PMID- 2101193 TI - [The HLA-B27 antigen and rheumatic diseases]. PMID- 2101194 TI - [Oral lichen planus]. AB - Oral lichen planus is a chronic inflammatory disease of adult onset. The etiopathology is based on a reaction against immunologically altered keratinocytes. There are variable forms of this condition, which at times make recognition difficult. Remissions are frequent. Associated oral carcinoma subsequent to the initial diagnosis of oral lichen planus is observed. Therefore all patients with oral lichen planus should be carefully evaluated and followed periodically. PMID- 2101195 TI - [Mastication rehabilitation via dysgnathia surgery and simultaneous implantation]. AB - Within the last 2 years 26 endosseous implants have been used in combination with orthognathic surgery in the maxilla and mandible. The results show, that endosseous implants can be used simultaneously with orthognathic surgery. This helps to treat dysfunctions often seen in partially edentulous patients that undergo orthognathic surgery and at the same time reduce the risk of relapse by achieving stable occlusion. PMID- 2101196 TI - [Prognosis in buccal cancer: up-to-date review]. PMID- 2101197 TI - [Priorities and treatment principles in maxillofacial trauma]. AB - The outline of therapeutic priorities in case of maxillo-facial traumatism may be divided in three different stages according to the need of acute urgent, urgent and necessary intervention. Acute urgent therapy is called for when the bleeding of the arteria carotis externa or the maxillary artery cannot be quenched or when the superior airways are obstructed by the soft tissues of the tongue or the floor of the mouth. A description of the therapeutic attitude in such cases is given. Urgent therapy should be given within 8 hours after the accident and mostly consists in the immobilisation of bony injuries and definite care of soft tissue lacerations. Necessary therapy includes the final surgical treatment such as osteosynthesis by titanium mini-plates. More specific problems like frontobasal fractures and fractures of the orbital floor are described separately. PMID- 2101198 TI - [The Wurzburg titanium miniplate system: evaluation of 3-year utilization]. AB - In this article the use of Titanium miniplates in the maxillo-facial surgery is being examined. After a literature-study concerning the qualities of Titanium and the advantages, disadvantages aswell as indications of the miniplates, the stability of osteotomies using this system is being traced, aswell as its eventual developments. From this research it becomes clear that the miniplates indeed contribute to greater stability of the skeletal fixation in maxillo-facial surgery. PMID- 2101199 TI - [Infections along trans-mucosal fixation wires]. AB - In a retrospective investigation the frequency and reasons for infections along internal fixation wires used in trauma patients was studied. A group of 628 trauma patients of the period 1985-1990 was reviewed. In 50 patients out of this group internal wires were used that perforate the oral mucosa. In 11 cases an infection was noted. The trauma group was than compared with 634 patients who underwent orthognathic surgery in the same period. In this group only 3 patients developed an infection along an internal fixation wire. After analysis of the date it seemed that the use of preventive antibiotics and a good oral hygiene prevents infections along intern wires. PMID- 2101200 TI - Biological preparations with clinical efficacy in the prevention and therapy of allergic syndromes. PMID- 2101201 TI - Bacterial agents associated with bronchopulmonary disorders in eastern Nigeria. AB - Altogether 16,539 sputum specimens were examined microbiologically from 1980 to 1984. Out of these 12,588 were screened by Ziehl-Neelsen's staining technique and 782 were (6.3%) found AFB-positive. Age and sex distributions of the AFB-positive individuals were statistically significant (at 0.05), incidence being most prevalent among those 20 years and above (90.2%) and among males (61.2%). From other specimens cultured, non-AFB organisms were isolated at the following frequencies: coliform-like organisms (15.1%), Streptococcus pneumoniae (55.5%). Klebsiella pneumoniae (5.3%), Streptococcus pyogenes (3.9%), Pseudomonas aeruginosa (3.4%), Haemophilus influenzae (3.0%). Proteus Spp. (0.7%) and Escherichia coli (0.5%). The antibiogram of these isolates revealed a high incidence of multiple antibiotic resistance, a situation that has most probably arisen from the high degree of antibiotic misuse in Nigeria. PMID- 2101202 TI - Prospects of applying some scientific data obtained in the field of cellular and humoral immunity in allergic diseases. Prophylaxis and treatment. PMID- 2101203 TI - Study of specific immune response to unadsorbed concentrated tetanus vaccine administered by intradermal route to non-immunized persons in the last ten years. AB - Investigations of anti-tetanus response, in 404 subjects, most of them aged 60, being non-immunized for at least 10 years, stressed out the fact that 28.7% were not protected and 6.18% presented a protecting titer of 0.01 IU/ml, evaluated by "in vivo" protection test in mice. Some subjects were immunized with unadsorbed Tetanus vaccine (10 Lf/0.1 ml/dose) by i.d. route, using Jet-injector, and the others with adsorbed Tetanus vaccine (0.5 ml/dose), by i.m. route, using the needle and syringe. The vaccines were well tolerated and adverse reactions were not recorded. After 30 days, a single vaccine dose produced a protecting effect in 97.45% of non-protected subjects, belonging to i.d. immunized group, and also in 93.33% belonging to i.m. immunized group. 30 days after the administration of a second dose, protection set up in all subjects, no matter of vaccine type and administration route used. For a continuous reduction of tetanus morbidity, the authors suggest a specific periodical immunization of non-protected persons, selected by serological screening, using unadsorbed Tetanus vaccine, administered by i.d. route by means of the Jet-injector. PMID- 2101204 TI - Spectrophotometric assay of the interaction between malaria erythrocyte lysates with methylene blue and neutral red dyes. AB - Changes of oxidative processes induced in mouse erythrocytes by Plasmodium berghei were studied in the presence of methylene blue, neutral red or of both cationic redox dyes. The results are discussed in terms of redox and metachromatic modifications of the dyes which are produced by malarial and normal erythrocyte lysates. PMID- 2101205 TI - The incidence and epidemiological significance of Campylobacter jejuni/coli serotypes in Romania. AB - The distribution per serotypes of 401 Campylobacter strains was studied by Lior's procedure, 241 strains being identified as C. jejuni (60.1%) and 160 as C. coli (39.9%): out of these 329 were of human origin (82%), including 225 C. jejuni and 104 C. coli, and 72 were isolated from fowls and swine (16 C. jejuni, 56 C. coli). Out of the total of 401 strains, 363 (90.5%) were typable. Among human strains, 32 serotypes were identified, more frequently encountered being (in a decreasing order) 29, 4, 21, 2, 1, 9, 59, 44, 36, 48, 28, 8, 47, 5, 11, 57, 10, 32, 55 which sum up 89.5% of the 296 typable strains. Within C. jejuni species, serogroup 4 was the predominant one and for the C. coli one--29. Animal strains were distributed into 16 serogroups out of which 29, 26, 48, 55, 44 were more frequently encountered. The serogroups identified among animal strains were encountered, with a single exception, among human strains, too, but with a different frequency. The importance of serogrouping as an epidemiological marker, was confirmed by serogroup identity of the strains within some family foci, by the oneness, as serogroups, in the case of repeated isolations from the same patient as well as by establishing an epidemiological diagnosis, in the case of an epidemic, occurring among the members of a given community. PMID- 2101206 TI - Nuclear bodies and virus-like particles in gingival tissue of periodontopathic patients. PMID- 2101207 TI - Standardised reproducible hemagglutination test technique for simple veterinary clinics in developing countries. PMID- 2101208 TI - General mechanisms of carcinogenesis and anticarcinogenesis. PMID- 2101209 TI - Isolation of motile aeromonads from foods of animal origin. AB - The purpose of this work was to select an available medium for Aeromonads isolation as well as to point out the Aeromonads presence in different foodstuffs of animal origin. Out of 15 tested media for Aeromonas isolation, two media, were selected: DFS as control medium and AGOS medium, both giving superposable results. 404 samples of foodstuffs of animal origin were examined; Aeromonads testing was performed qualitatively and quantitatively. 142 samples with a positivity percent of 51.40% were qualitatively tested. 262 samples with a positivity percent of 48.85% were quantitatively tested. PMID- 2101210 TI - Isolation of Yersinia group in human infections, animals and environment factors. AB - The presence of Y. enterocolitica and Y. pseudotuberculosis was studied in 4479 enteritis cases, 430 children, presenting appendicular syndrome, and 60 hospitalized patients with arthritis and Reiter syndrome. Y. enteritis was detected in 41 (0.9%) enteritis cases, 15 (3.4%) appendectomized children and 5 (8.3%) arthritis cases. Antibodies to Y. pseudotuberculosis were detected in 2 (3.3%) arthritis patients. Y. enterocolitica was isolated in swine, fish and environment factors (water, soil, food). Y. pseudotuberculosis was isolated in soil. The isolated strains belonged to biotypes 1, 2, 4 and serotypes 0:3; 0:5; 0:5.27; 0:5, 6, 7, 8; 0:6; 0:9; some were non-typable and polyagglutinable. The strains were sensitive to bacteriophages for Yersinia, obtained in our laboratory. PMID- 2101211 TI - Bioeffects of the plant Mahonia sempervirens. AB - Water extracts of mature fruits of Mahonia sempervirens possess four biological properties: hemagglutinin, hemolysin, complement antagonism and antistreptoccocal activity. Partial characterization of the crude extract was carried out by barbital-mediated spectrophotometry, polyacrylamide gel electrophoresis, thin layer chromatography and interaction chromatography. Fractionation of the Mahonia extract by ionic exchange static adsorption resulted in the quantitative separation of the fruit red pigment with recovery of the entire anticomplementary activity and indicated that the complement inhibitor was different from the aggregating and lytic properties. PMID- 2101212 TI - [Osteoid osteoma. A scanning electron microscopic study]. AB - The mineralization process of the osteoid osteoma, after removal of the organic matrix from the specimens by treatment with 6% sodium hypochlorite, has been studied by SEM. The process was characterized by calcified nodules or calcospherites, variable in size from 0,1 to 2 microns, embedded among randomly oriented collagen bundles, which delimited trabeculae of sponge primary bone. Numerous osteocytic lacunae, in various degrees of development, in the mineralizing front were present. The ultrastructural feature of the mineralization in osteoid osteoma reflected a pattern of nodular and collagenous calcification, essentially similar to primary calcification, characteristic of rapidly developing woven bone. PMID- 2101213 TI - [Osteoid osteoma of the foot]. AB - We relate about our direct clinical experience on 8 cases of osteoid osteoma localized in the bones of the foot. Some atypical appearances, clinical and roentgenographic, of the osteoid osteoma in this bony district may sometimes cause problems in diagnosis and localization, which are exposed and discussed in this paper. Particularly, we underline the importance of bone scan in the detection of the lesion. PMID- 2101214 TI - [Chondromas and chondrosarcomas of the hand: their surgical treatment and the long-term results]. AB - Authors show various techniques utilized in surgical treatment of forty-nine hand chondromas, specifying indications, advantages and long term results, and refer on one case with beginning malignancy and one case of chondrosarcoma in the hand. By analysis of clinical, roentgenographic, pathological and evolutive pictures they discuss on their conclusions in malignancy criteria, reporting their surgical choices in treatment of hand chondrogenic malignant tumors. PMID- 2101215 TI - [Chordoma (a review of 11 cases)]. AB - Eleven cases of chordoma, localized at sacrum (3 cases), lumbar spine (6 cases), cervical spine (2 cases), are reported. Authors describe clinical and pathological findings of the tumor and underline peculiarity of spinal localization and difficulty of diagnosis, often delayed, particularly in sacral spine localizations. Radiotherapy and chemotherapy give poor results while surgery can be employed in the treatment on account of the slow evolution and of the not very frequent aptitude of the tumor to give metastases. However peculiar localization into the sacral spine allows to remove the whole tumor if only it is localized below the 2nd sacral vertebra; authors present such a case treated by means of subtotal resection of sacrum and coccyx. In proximal sacral localizations and in other spinal localizations, surgery is a palliative procedure and can only slow down the evolution of the tumor; recurrence is a rule, even in association with radiotherapy. However surgical treatment must be often performed because of myeloradicular involvement. PMID- 2101216 TI - [The neoplastiform aspect of a case of pigmented villonodular synovitis of the knee]. AB - A case is presented of pigmented villonodular synovitis of the knee, macroscopic neoplastiform in appearance. The histologic examination leads to believe in a granulomatous rather than neoplastic nature of the process. The cause certainly is neither traumatic nor bacteriologic, but most probably dismetabolic lipidic. The neoformed mass, singular for its remarkable dimensions (12 cm. in length), nodular in appearance, pedunculated, had not yet provoked, at the time of operation, secondary osteocartilaginous and capsular-ligamentous lesions. At follow-up, more than 11 years later, no signs of relapse were noted and the radiographic examination was negative. PMID- 2101217 TI - [Osteosis due to primary hyperparathyroidism. The SEM ultrastructural features of the periosteal and endosteal surfaces]. AB - The study of four cases of osteosis caused by primary hyperparathyroidism, tree female and one male, which have undergone surgery for pathological fractures in met-epiphysis bone, allows to analyze with the help of scanning electron microscope modifications occurring in periosteal and endosteal bone matrix. The periosteal surface appears abundantly furrowed by large and deep canals, irregularly joined together. Areas of resorption, these at rest and these of osteodeposition are distributed in changeable but regular way. The bone turnover of endosteal side is particularly accentuated. This surface contains the bone trabeculae residuals and is widely marked by deep Howship's lacunae, which show intense osteoclastic activity. It seem that osteocytes cells participate actively in the process of osteolysis, widening the lacunae and small canals which appear to be surrounded by calcospherites arranged in irregular way. Osteogenetic activity, with large areas of deposition, is very intense, as a defence attempt against osteolytic resorption process. PMID- 2101218 TI - [The modality of endoconnective ossification on cartilaginous substrate: observations on the long bones in the embryo]. AB - The authors conducted a histologic study on the modalities of ossification of the "diaphyseal osseous ferrule" in embryos between the sixth and eighth week of intrauterine life: the ossification of this "diaphyseal osseous ferrule" presents some peculiarities compared to that of other areas: it occurs with the modalities of periosteal ossification, exploiting, however, a cartilagenous substrate. In addition, the authors compared the ossification of the diaphyseal ferrule to that of the "perichondrial ferrule of the layer of ossification", examining histologic sections of embryos in the 25th week of intrauterine life. PMID- 2101219 TI - [Bone transplants in prosthetic knee surgery]. AB - The authors refer on their experience using bone grafting of tibial defects in total knee arthroplasty. The advantages, the technique, the casuistry and the results of this method are illustrated. PMID- 2101220 TI - [Bone mass in males. A comparison between dual-photon densitometry of the lumbar spine and the whole body]. AB - In order to evaluate the validity of a new method for measuring the whole body mineral content in diagnosing senile osteoporosis we studied 3 groups of male subjects: the first one composed by 40 young healthy subjects (mean age 24.7 years), the second composed by 40 normal patients (mean age 51.3 years); the 3rd group consisted of 26 elderly patients affected with typical osteoporotic fractures (mean age 77 years). All of them underwent a measurement of the spine as well as whole body mineral content performed with a dual photon absorptiometer. The measurements showed a decreasing in mineral content in the second versus the first group but a high correlation coefficient between spine and WB measurements characterized both groups; a striking decrease of it (r = 0.22) was found in the 3rd group. The relative unreliability of the spine measurement in elderly is probably due to the age-linked anatomical alteration. We therefore conclude that WB measurement must be considered the method of choice for the detection of senile osteoporosis. PMID- 2101221 TI - [Variations in the rate of erythrocyte sedimentation in the postoperative orthopedic and traumatologic course and their clinical significance]. AB - The authors report their results on E.S.R. variations within the first month post surgery in 38 traumatologic and orthopaedic patients, to evaluate the time of normalization and its attendibility in case of infection. Normalization was found within the first month postoperatively, without significant differences between orthopaedic and traumatologic patients. They think that the E.S.R. becomes significant on the control of postoperative subacute infection after the third postoperative day and propose E.S.R. evaluation after this period. PMID- 2101222 TI - [The ultrastructural aspects of the synovial intima and subintima in arthrosis]. AB - Synovial membrane removed surgically from patients during developing degenerative joint disease were studied under a scanning and transmission microscope. The results show that the synovial membrane is folding into villi of average dimensions (microvilli and macrovilli) which project into articular cavity. In regard to the villi, the morphology is locally changeable, with the atrophic sclerotic areas alternated with hyperplastic areas, but topographically well defined. In the last ones, structural modifications of the intima layer, are characterized by hypertrophy of B synoviocytes, which are constituent and predominant cells in comparison with other cell-types. In the subintima around ectatic vessels, the linfomonocitary inflammatory infiltrations may be found. These alterations are the results of active biological process and because of this synovial membrane is of big importance in developing of osteoarthritis. PMID- 2101223 TI - [The activities over one year of the first aid unit of the Florence Orthopedic Trauma Center: a statistical analysis]. AB - The characteristics of all the traumatic cases treated at the emergency unit of C.T.O. Hospital in Florence are here described. The year 1985 was taken as a sample to be compared to the previous statistics obtained in the past. The authors found an increase in the number and severity of the traumatic cases, particularly in old patients and localized in the extremities (hand and foot). PMID- 2101224 TI - [An anatomicoclinical analysis of the synovial plica syndrome]. AB - The authors describe embryology and anatomy of synovial plica of the knee joint. They propose a clinic and pathogenic classification and after examining the diagnostic problem of plica syndrome, analyze their long-term results after surgical treatment. PMID- 2101225 TI - [The conservative treatment of capsular-ligamentous lesions of the acromioclavicular joint]. AB - After a brief introduction, the authors experience on 71 capsular-ligamentous traumatic lesions of the acromion-clavicular articulation is reported. Statistical considerations are made and clinical results, obtained after three years from conservative treatment (all lesions were lifting in Allmann's standards), are exposed. PMID- 2101226 TI - [Sports pathology of the shoulder: its imaging diagnosis]. AB - Success and diffusion of various sports have produced more frequent capsular ligamentous lesions of the shoulder. Diagnosis up to now has relied on traditional radiology using many projections to demonstrate extremity lesions and their congruences; however for capsular-ligamentous lesions, arthrography in used successfully. Since the last few years new investigating methods are used (U.S., C.T., M.N.R.). After examining benefits of each diagnosing method compared to traditional radiology, the authors conclude that traditional radiology still has a pre-eminent role in diagnosing sports pathology of the shoulder. PMID- 2101227 TI - [Arthrodesis of the tarsal tibia for the outcomes in fractures of the collum tali. A review of cases and long-term follow-up]. AB - In the wards of the CTO Hospital in Florence, isolated arthrodeses of the tarsal tibia for ankle fractures, or their effects or complications, have been performed on 29 patients in the past 13 years. Of these 29 patients we were able to personally check up on 23, with a follow-up time ranging from one to thirteen years. The patients we followed-up on had been operated on using the Scaglietti technique or its variations in 15 cases, the Charnley technique in 7 cases, and the fixation according to Ilizarov in one case. We examined the pre-operatory clinical-radiographic conditions and the surgical techniques utilized with all of their advantages, disadvantages, limits, and pre and post-operatory complications. In the follow-up studies, for instance, in addition to the subjectivity of the patient we clinically evaluated the commemorative signs and post-ambulatory adaptation phenomena as a function of the residual degree of equinism and, radiologically, the condition of the arthrodesis and the articulation proximal to the tarsal tibia. Tibio-tarsal arthrodesis, notwithstanding the inconveniences common to all types of arthrodesis, has in essence retained its validity regarding the seriously crippling effects of ankle fractures. PMID- 2101228 TI - [Rare skeletal pathology: the diagnostic problems in the first year of life]. AB - The authors report a series of affections which determine diffused modifications of the skeleton during early childhood. More common pathological forms are dealt with, of relatively simple diagnosis, and having pathological pictures which based on frequency, means of occurrence, and clinical-radiographic aspects, are rarely observed, and difficult to diagnose. Based on several clinical cases, the authors report problems related to diagnosis, emphasising the meaning of various radiographic pictures and the value and choice of hematochemical tests aimed at selecting patients in whom biopsy is required. PMID- 2101229 TI - [Torsional changes in the lower limbs in childhood]. AB - Based on their observation of approximately 1000 patients aged from 4 to 14 years and on a comparison of their experience with the data reported in the literature, the authors discuss the problem of modifications in torsion of the lower limbs during pediatric age. After a brief discussion of anatomy and the natural progression of the angle of femoral anteversion and tibial torsion, they stop to accurately describe the most frequently occurring defects in torsion, both isolated and combined. After affirming the contribution that axial vision has made to an understanding of the subject, they emphasise the current usefulness of the method in cases in which a clinical examination allows for doubts to persist and, in particular, if qualitative and quantitative diagnosis is required in relation to the therapeutic protocol. The authors conclude by suggesting that therapy be carried out during the growth age (much before 14 years of age) while they suggest waiting until skeletal maturity in order to make a general evaluation and to decide on treatment of combined defects. PMID- 2101230 TI - [Perichondrial changes in the evolutionary course of traumatic lesions of the epiphysis in growth]. AB - The authors conducted an experimental study aimed at defining the response of the perichondrium to traumatic stimuli. Thirty rabbits were used, subdivided into two groups: in the first group, the perichondrium was submitted to indirect trauma (fracture of the growth nucleus); in the other, to direct trauma (decortication of th perichondrium). We observed that the lesions constitute a stimulus for cellular proliferation with successive differentiation depending on various procedures. The mesenchymal cells of the deeper layer of the perichondrium reveal a tendency towards differentiation in a chondroblastic sense; the portion of these cells which face the metaphysis are generally differentiated to constitute typical cytotypes of the periosteum, giving way to membranous ossification phenomena. The more external layer reveals proliferation of its fibrovascular component. This experimental model allowed us to emphasise the proliferative tendency of so-called perichondrial cells (those of the deep layer). Thus, their role in providing the growth cartilage of new chondrocytes was confirmed, contributing to the transverse development of the metaphysis. PMID- 2101231 TI - [Unicompartmental prostheses: an alternative to osteotomy? When?]. PMID- 2101232 TI - [Direct skeletal traction by a wire with san olive-shaped plug]. AB - A new method of treatment of dislocated fractures and apophyseal fractures, using direct traction by pins on the bone fragments, and cast is presented. The authors describe the technique employed and report the results of the 22 cases treated. PMID- 2101233 TI - [Long-term scintigraphic follow-up study of the hip prosthesis]. AB - The authors emphasize the importance of the bone scan in long-term follow-ups of total hip arthroplasty and describe some technical details of the examination. The changes revealed in the bone scan are confirmed by the operative report. Even though the number of patients in the study was relatively small, the fact that the bone scan taken of patients with cementless total hip replacements revealed no pathological changes is considered significant. PMID- 2101234 TI - [The initial findings in 50 cases of the cementless hip prosthesis]. AB - The authors, after putting forth several biomechanical premises, discuss their experience in total hip arthroplasty (THA) using a PCA-type press fit cementless prosthesis with partial Madreporic covering. Several cases which demonstrate the versatility of this type of replacement are discussed in depth. Even though the short follow-up precludes definitive conclusions, use of cementless total hip replacements must be considered a valid option in the future, especially in cases of early onset of hip pathology. PMID- 2101235 TI - [The long-term results of the Putti-Platt intervention]. AB - The results of surgical intervention in 183 patients operated on for recurrent shoulder dislocation from 1962 to 1985 are reported. After an average follow-up of 10 year (min. 3, max. 24), 115 patients (117 shoulders) were evaluated. The Putti-Platt technique was used in 65 patients and Scaglietti's modified technique in 52. Results were evaluated on the basis of pain, mobility, strength, stability, function and subjective opinion of the patient. External rotation was measured in adduction as well as in abduction at 90 degrees. The results were excellent or good in 90% of cases. Almost all the athletes returned to the same level as before dislocation. In 2.5% of cases the results were poor, due to excessive limitation of external rotation which caused severe osteoarthritis of the glenohumeral joint. Recurrence of dislocation occurred in 2 patients. PMID- 2101236 TI - [The role of osteotomy in the therapy of the arthritic genu varum]. AB - The good results achieved with osteotomy in the treatment of arthritic varus knee lead the authors to pinpoint some frequently controversial aspects that are important for the attainment of an excellent outcome. The study consisted of 46 patients, each subjected to valgus osteotomy. The site of the tibial osteotomy should be above the insertion point of the patellar tendon in order to better guarantee stability and healing. For mechanical reasons, high metaphyseal peroneal osteotomy is preferred over other methods such as diaphyseal osteotomy, excision of the peroneal head, and proximal tibioperoneal syndesmotomy. Both osteotomies can be done through a single anterolateral incision, without risking injury to the lateral popliteal sciatic nerve. The preferred method of osteotomy is to cut a noncuneiform linear rima with the osteotome and perform the angular correction at the joint of the metaphyseal spongy bone. The osteotomy is then stabilized with staples and a cast for a period of 40 days. Overcorrection past the physiological valgus deformity is necessary in order to move the weight bearing axis onto the lateral hemirima; the degree of surgical correction should be calculated on the basis of orthostatic radiographs. Good clinical results are always accompanied by the following radiographic developments: opening of the medial articular hemirima, improvement of the subchondral bone sclerosis, and reappearance of the outlines of both the spongy bone and the subchondral bone lamina; all these are signs of good bone adjustment made possible by the reinstatement of mechanical equilibrium in the knee. PMID- 2101237 TI - [The foot in rheumatoid arthritis]. AB - Because of its high incidence of rheumatoid arthritis, the foot is probably the best place to study this pathology. Timely diagnosis is very important considering the high risk of disability. On the basis of both other studies and first-hand observations, the particular clinical and radiographic characteristics of rheumatoid arthritis of the foot are analyzed, differentiating it from the same disease in other joints. The research and comparison of these particular aspects helped with the overall clinical evaluation of early-diagnosed rheumatoid arthritis, that is before the development of reabsorption phenomena, bone damage, deformities, and ankylosis of the joints of the foot. PMID- 2101238 TI - [Neurogenic deformities of the foot due to congenital malformations of the lumbosacral spine. Their clinical and therapeutic characteristics]. AB - The authors illustrate the different types of nervous disorders of the foot caused by congenital deformations of the lumbosacral spine. They classify these clinical forms according to the level of the neurological lesions, although emphasizing that more complex neurological damage may cause very atypical deformities that are difficult to classify. Today the treatment of nervous disorders of the foot caused by congenital deformations of the lumbosacral spine seems almost promising when compared to neurological and urological problems which have therapeutic priority. Possible methods of surgical correction, as well as indications that differ according to the age of the patient and the type and extent of the deformity, are discussed. These deformities of the foot evolve very quickly; treatment must be timely or reduction is difficult. Furthermore, their peculiar tendency to relapse necessitates periodic comprehensive follow-up exams and regular maintenance therapy (orthetic and physiatric). Special care must be taken before and during treatment to prevent trophic skin lesions. For this reason, solutions other than casts (external fixation, for example) may be preferable for the maintenance of the correction. The treatment of these deformities, whether conservative or surgical, should aim primarily to achieve adequate plantar support for future aided or autonomous ambulation. PMID- 2101239 TI - [Clinical experience with automated percutaneous diskectomy]. AB - Percutaneous automated aspiration discectomy (Nucleotome, Surgical Dynamics) is a new procedure for treating herniated lumbar discs. In a series of 35 patients, followed-up after 6 months, the overall success rate was 74%. 19 patients resumed work 4 weeks after surgery. In 6 patients the interventions were judged as failures and required reoperation (laminectomies). All the patients obtained complete relief. Meticulous selection of patients for percutaneous lumbar discectomy is the key to success. No intra-operative or post-operative complications occurred. PMID- 2101240 TI - [Automated percutaneous nucleotomy: an analysis of the clinical results in relation to the morphological characteristics of the intervertebral disk hernia]. AB - Thirty-five patients, selected according to the criteria of Onik and operated on by automated percutaneous lumbar discectomy, were evaluated in a retrospective study in order to assess correlation between clinical results and characteristics of the disc herniation and the value of current imaging techniques in selecting patients for percutaneous discectomy. Percutaneous discectomy is not indicated for narrow, postero-lateral herniated discs (3 cases, 3 failures). Two-thirds of the failures are consequences of inaccurate CAT scan images (false-negative images of subligamentous migration of the herniated disc). PMID- 2101241 TI - [Posterior osteosynthesis in C1-C2 instability]. AB - This is a retrospective study of 8 cases of instability of the C1-C2 segment caused by R.A. or non-union and treated by posterior stabilization with wire loops and bone grafts. The authors reported good results in patients with mild recent neurological involvement and/or radiographic instability of the segment (posterior subluxation of the dens greater than 1/3 of the A-P diameter of C1 or tilting of the dens greater than 30 degrees). The death of a patient with non union of the dens and severe neurological involvement due to respiratory palsy leads the authors to regard severe long-term neurological involvement (quadriparesis) a contraindication for this type of procedure. PMID- 2101242 TI - [The centralized diagnosis and therapy of bone and soft tissue tumors. European Musculoskeletal Oncology Society]. PMID- 2101243 TI - [Epiphyseal and apophyseal localizations of chondroblastoma (a study of 19 case histories]. AB - The authors report their experience in epiphyseal and apophyseal chondroblastoma. A double localization in both proximal humeral epiphyses is presented. Four apophyseal localizations are studied and particular attention is given to histological and ultrastructural features of neoplastic cells. PMID- 2101244 TI - [Pathological fractures and prefracture osteolytic lesions due to metastases located in the femoral diaphysis: a clinico-radiographic study, a case history review and considerations of treatment evolution]. AB - The authors reviewed the clinical and radiographic documentation of 44 cases of metastatic lesion in the femoral diaphysis, all treated during a 15-year period at the Centro Traumatologico e Ortopedico of Florence. The results obtained with both initial nonoperative treatment (casts) as well as subsequent intramedullary fixation are evaluated with great care. The evaluation of the results in terms of survival was not possible for several reasons, not least of which the recent progress made in radiation-chemo-hormonal therapy for tumors. Despite the precarious general condition of most of the patients surgical treatment did not cause intraoperative or immediate postoperative mortality. Overall, the postoperative complications were not serious and were compensated for by good progress in systemic therapy, good nursing, and in some cases recovery of autonomy. PMID- 2101245 TI - [The prevention and treatment of skeletal deformities in fibrous dysplasia]. AB - Fibrous dysplasia generally leads to skeletal deformity over time, particularly when the lower extremities are affected. The authors describe their experience in this field, proposing mainly preventive treatment of progressive deformities and pathological fractures. They prefer intramedullary nailing, which by strengthening the affected bone allows free and early mobilization of the limb. Moreover, full weight-bearing prevents the onset of "ex non usu" osteoporosis, which is quite often responsible for pathological fractures. PMID- 2101246 TI - [Intramedullary nailing with a Rush pin in the treatment of diaphyseal humeral fractures]. AB - The authors discuss their 20 years of experience in the treatment of diaphyseal fractures of the humerus with Rush-type intramedullary nailing. The various operative and nonoperative methods for the treatment of this type of fracture are critically analyzed. The results were excellent in 60.5% of the cases, good in 29.6%, and poor in only 9.9%, in which healing was over 4 months late and a hypotrophic callus was present. The advantages of this treatment are as follows: adequate reduction of the fracture, simplicity of execution, good results, and shorter period of immobilization compared to other methods. PMID- 2101247 TI - [The results of a resection intervention in isolated fractures of the radial head]. AB - The results of radial head excision were studied in 33 patients with isolated fracture of the radial head. The follow-up period ranged from 1 to 19 years (mean 9.5 years). Overall results were excellent or good in 25 patients (76%) and fair or poor in 8 patients (24%) with functional limitation of the elbow. Range of motion was greatly limited in those patients who had a myositis ossificans or a radio-ulnar synostosis. Periarticular ossifications were observed in 17 elbows (54%) and subluxation of the inferior radio-ulnar joint in 20 wrists (60%). Excision of the radial head is the treatment of choice for comminuted isolated fractures of the radial head, even if in some patients limited elbow function should be expected. PMID- 2101248 TI - [Subcutaneous rupture of the Achilles tendon (a review of 42 cases treated by tenoplasty with fascia lata)]. AB - The authors relate their experience in the treatment of subcutaneous disruption of the Achilles tendon with tenorraphy and neutering tenoplasty by quadriceps muscular aponeurosis. The results obtained in 33 patients confirm the effectiveness of this method. PMID- 2101249 TI - [Thalamic fractures of the calcaneus. The authors' experience]. AB - The authors refer their experience in management of thalamic fractures of the heel. Their series includes 22 patients with 24 fractures and comprises the 12 year period 1975-87. They assess the results based on radiological, clinical, functional and occupational criteria, emphasizing the role of the posterior subtalar joint, which imposes an anatomical reconstruction on the orthopaedist, since the final results are conditioned by its arthritic degeneration. Complex fractures with important displacement need surgical treatment with reduction and synthesis. In simple fractures with or without slight displacement, conservative treatment using cast immobilization is now the treatment of choice. PMID- 2101250 TI - [25 years of the activities of the Florence Orthopedic Trauma Center (May 1962 May 1987)]. PMID- 2101251 TI - Effect of a mouthrinse containing triclosan and a copolymer on plaque formation in the absence of oral hygiene. AB - Twenty male and female adult subjects were entered into a 7-week, double-blind clinical study to determine the effect on plaque formation of a mouthrinse containing 0.03% [corrected] triclosan and 0.25% of a copolymer of methoxyethylene and maleic acid, as compared to 1) a water placebo mouthrinse, 2) a matching alcohol placebo mouthrinse, and 3) Plax antiplaque pre-brushing dental rinse. The subjects were stratified according to their initial plaque scores and assigned in a type of randomized block design (repeated Latin square), so that each subject received each of the four mouthrinses only once for 1 week during the study. The subjects did not use any other oral hygiene procedure (including use of a toothbrush and dentifrice) during the 1-week period of time when they rinsed with their assigned mouthrinse product. The results indicated that use of the triclosan/copolymer mouthrinse provided a 49.8% reduction in supragingival plaque formation compared to the water placebo mouthrinse. The difference was statistically significant at the 99% level of confidence (P less than .01). Similarly, the use of the triclosan/copolymer mouthrinse provided a 47.6% reduction in supragingival plaque formation compared to Plax antiplaque pre brushing dental rinse. The difference was statistically significant at the 99% level of confidence (P less than .01). The results further indicated that use of the triclosan/copolymer provided a 31.2% reduction in supragingival plaque formation compared to the alcohol placebo mouthrinse. The difference was statistically significant at the 99% level of confidence (P less than .01). PMID- 2101252 TI - Unilocular radiolucency associated with an impacted tooth. PMID- 2101253 TI - Frequency of the -alpha 3.7 thalassemia deletion in the non-white Cuban population. AB - DNA analysis of the alpha-globin gene cluster showed that the frequency of the alpha 3.7 deletion in the non-white cuban population is about 0.12, in agreement with a 47% admixture of the original African slaves introduced in the island. In the S-S homozygotes the frequency is slightly higher (.18), probably due to a selective advantage produced by the presence of alpha-thalassemia in sickle cell patients. PMID- 2101254 TI - Genetic polymorphisms in the Croatian ethno-linguistic minority of Italy. AB - Phenotype and gene frequencies of twelve genetic markers (ABO, RH, MNS, ACP1, ESD, PGD, PGM1, PGM2, HB, ALB, CP and HP) of the three Croatian communities (Acquaviva Collecroce, Montemitro and S. Felice del Molise) living in Southern Italy are reported. From the comparison with the surrounding Italian population and with Balkan populations, some instances of still incomplete genetic admixture can be inferred (ABO*A and O, ESD, PGD and PGM1). PMID- 2101255 TI - Red cell enzyme polymorphisms in the Balearic Islands. I. Substructuring of the Mallorca population. AB - A sample of 2143 individuals belonging to six natural geographic regions from Mallorca (Balearic Is. Spain, 39.5N, 3.0E) was studied for the red cell enzyme polymorphisms: Esterase-D (ESD), acid phospatase-1 (ACP1), glyoxalase-I (GLO1), phosphogluconate dehydrogenase (PGD), phosphoglucomutase-1 (PGM1) and adenylate kinase (AK1). The following gene frequencies were obtained: ESD*2'3 = 0.142, ACP1*A = 0.248, ACP1*C = 0.027, GLO1*2 = 0.529, PGD*C = 0.010, PGM1*2 = 0.221 and AK1*2 = 0.033. Most of these gene frequencies were in Hardy-Weinberg equilibrium. The subpopulation of "La Muntanya" showed significant differences for some allozymes respect to the others, in accordance with its geographic peculiarity. PMID- 2101256 TI - Red cell enzyme polymorphisms in the Balearic Islands. II. A comparison based on multivariate analyses. AB - A sample of 2143 individuals from Mallorca, coming from six geographic regions of this island: "Es Raiguer", "La Muntanya", "Es Pla", "Mijgorn", "Llevant" and "Palma", as well as 390 individuals from Eivissa island have been studied for the following six red cell enzyme systems: Esterase-D (ESD), acid phosphatase-1 (ACP1), glyoxalase-I (GLO1) 6-phosphogluconate dehydrogenase (PGD), phosphoglucomutase-1 (PGM1) and adenylate-kinase (AK1). The data were processed by means of multivariate statistical procedures: principal components, factorial correspondence and cluster analyses. The results indicate that ACP1 and ESD were the most suitable systems for the characterization of these caucasian populations, while GLO1 was important when different ethnic groups were included in the analyses. The Balearic gene frequencies fell within the European standard. Slight genetic distances were detected among the different Balearic populations, notably with the exception of the high differentiation of "La Muntanya". PMID- 2101257 TI - Population genetic studies on Jews. I. The alpha 2HS serum glycoprotein, a polymorphism strongly correlated with latitude. AB - A sample of Jews subdivided according to the birth-place of their parents or grand-parents have been examined for a large number of genetic markers in the course of a long-term project on the genetics of Jews. We report here the findings concerning 794 Jews studied for the AHSG polymorphism. All the subsamples were in Hardy-Weinberg equilibrium. A highly significant difference was found between Sephardic + Near East Jews and Ashkenazi (AHSG*2 frequencies: 0.184 +/- 0.015 and 0.258 +/- 0.016, respectively). For comparative purposes the data available on Caucasoids have been considered. It turned out that they were neatly arranged along a latitude-AHSG gene frequency cline (0.0092 of AHSG*2 gene frequency increase per degree of increase of latitude) in the explored 30 degrees 60 degrees range (r = 0.97; P much less than 0.001). Of the two Jewish frequencies that could be taken into consideration because of their sufficient sizes, that of the Near East + Sephardic Jews was perfectly in line with the above mentioned cline, while that of the Ashkenazi was somewhat displaced in the sense of being more similar than expected to the other, more southern, Jewish group. Since the only AHSG*2 frequency significantly displaced from the regression line is that of the Ashkenazi, whose ancestors lived until centuries ago in more southern areas, this finding is a strong confirmation of the observed cline. PMID- 2101258 TI - Molecular determinants of tooth development: a review. PMID- 2101259 TI - Mesenchymal cell growth factors. PMID- 2101260 TI - Development and outlook for a caries vaccine. PMID- 2101261 TI - Statistical management of data in clinical research. PMID- 2101262 TI - [Glass ionomer cementing in stomatological practice]. AB - Glass ionomers cements represent a cement system which develops by a reaction between a polyalchenic acid, usually a homo- or a copolymer of acrylic acid and a ion donor, usually an aluminium fluorosilicate glass. Introduction of these ionomers in the stomatological practice was determined by their remarkable adherence to dentin, by pulpal and parodontal biocompatibility, and because of the fact that they deliver continuously fluorine over a long period of time. These cements provide a good marginal sealing of the obturation. In the last years a new generation of glass ionomers cements has been introduced, that "Cormat" cements, in which the glass powder is intimately linked to a pure silver metallic powder by a synthetization process, and this provides a greatly increased resistance to abrasion, as compared to conventional glass ionomer cements. Presently glass ionomer cements have become increasingly known in the stomatological practice and they are used preferentially for base obturations, under obturations with composites on lateral teeth, in the treatment of mylolysis and for coronary erosions determined by brushing, which do not need preparation of retention cavities. They are also used for coronary reconstruction, and the treatment of atopical microcavities of occluding decay processes on the lateral teeth that have induced limited enamel losses. The perspective of these cements in the stomatological practice depends however on an improved translucency, which, for the present at least, does not match that of silicates and composites, as well as on an improved resistance to bending, and even the "Cormat" cements are inferior to silver amalgam which is used in the obturation of classical class II cavities. PMID- 2101263 TI - [A method for the determination of corroding factors of amalgams by electrical measurements]. AB - The study describes a method for the determination of corrosion kinetics of amalgams from the buccal cavity by measuring initial and evolutive electrical potentials in parallel with an evaluation of clinical factors. It also deals with factors which might be improved in this connection. The method was applied experimentally in 125 cases with restoration therapy with silver amalgam, and a digital milivoltmeter for direct current was used, of 0.2% precision class with silver chloride electrodes to which two probes have been adapted. The values determined varied between--320 and--82 milivolts. The advantages as compared with previously used methods are the following: an electrical measurement of resistance to corrosion of amalgams, and improvement of factors which influence corrosion. PMID- 2101264 TI - [Experimentation of apiarian preparations for the direct and the indirect capping of the dental pulp]. AB - With a view to extend the range of biologically active preparations for the direct and the indirect capping of the dental pulp the authors have used a paste made from an alcoholic solution of propolis and zincoxyde. The study was carried on in 150 teeth with indirect capping of deep cavities, and 50 teeth with direct capping. The evolution of the cappings was followed clinically, radiologically and morphologically. The results obtained showed that the paste with propolis exerts effects similar to those of zinc eugenate. The morphologic study of the indirect capping showed that secondary dentin developed shortly after the application of the paste, and that it was followed by the development of pulpolites and the sclerous transformation of the pulp. In teeth with direct capping a protective film developed at the opening of the dental chamber. With time the pulpal wound undergoes cicatrization by a process of fibrosis and there is a trend to remineralization. No areas of pulpal degenerescence were found the rest of the pulpal tissue, and this suggests that the paste is more histophilic than the pastes based on calcium hydroxide, with which an area of necrosis occurred at the opening of the chamber, and calcium and fibrous degenerescence occurred in the coronal pulp. PMID- 2101265 TI - [The effects of occluding dysfunction on marginal parodontopathies]. AB - Occluding dysfunction (occluding dysharmony, occluding trauma) is an important etiologic factor of parodontal disease. It is an integrating element of the destructive process which characterizes the parodontal disease. Occluding dysfunction does not trigger gingivitis, or the development of parodontal pouches, but it does exert an influence on the progress and the importance of parodontal pouches determined by local irritation due to tartar and to bacterial plaques. Occluding dysfunction and the inflammation of parodontal tissues are different processes which occur in the course of the same disease namely of marginal parodonthitis. The inflammation develops in the gums and propagates in the parodontal sustaining tissues. Occluding dysfunction (also known as occluding dysharmony or occluding trauma) occurs in the parodontal sustaining tissues, and both determine tissue destruction. Occluding dysfunction and inflammation become codestructive factors which are interconnected, and are both capable to determine clinical and radiologic changes which are typical for diseased marginal parodontium. Due to the fact that individuals have variable parodontal reactions to local irritation factors, and considering the fact that inflammation and occluding dysfunction occur together but with variable degrees of severity, it is possible that they will not determine in all cases intraosseus pouches with angular lesions, or crater-like lesions. However, when we are confronted with such lesions it is very likely that the combined effects of inflammation and occluding dysfunction are at the origin. PMID- 2101266 TI - [Aspects of professional hygiene in dental technical laboratories]. AB - Investigations on hygiene and sanitary conditions in a laboratory for dental techniques consisted in physico-chemical determinations on microclimate (temperature, humidity, air currents), determination of dust particles (suspended and sedimented), determination of gases (CO, CO2, NO2, NH3, SO4(2-), chloride ions), and determination of microelements (Fe, Cu, Zn, Ni, Cd). In certain conditions the concentrations for dust, NO2, NH3, SO2(4-), chlorine and Cu were above the maximal accepted levels. Measures should be taken for the prevention and for the elimination of these noxious factors by implementing optimal hygienic conditions (heat, humidity, ventilation), by reducing gas emanations, by using protections equipment (mask, eyeglasses, gloves), and by periodic controls of the health status of dental technicians. PMID- 2101267 TI - [Plastic surgery for losses of facial substance by cheek rotation]. AB - New diversified plastic surgery methods have been introduced into practice in the last decades, aimed at repairing the loss of facial tissues involving the upper lip (with or without co-involvement of the lateral parts of the nose), and the lower eyelid area, that cannot be repaired by flaps prepared in the surrounding regions. In view of avoiding the disadvantages of 2- or 3-stage techniques the authors have re-evaluated the method introduced by Esser in 1918 for plastic repair of the facial tissues by rotation of the cheek, which is economical, efficient, rapid, and elegant, providing fully satisfactory esthetic results. Two cases are presented, one with loss of facial tissue following removal of an achromic recidivating melanoma, and another one following removal of a recidivating baso-cellular carcinoma, in which this method was employed with excellent results. PMID- 2101268 TI - [Orthodontics problems of the first permanent molar tooth]. AB - Following a series of theoretical considerations on normal occlusion, and on the interrelationship between the dentomaxillary apparatus and the central nervous system the authors approach two practical aspects:--the effects of an early loss of the first permanent molar tooth in the autochtonous child population, and--the solving of occluding changes in the sagittal plane. With regard to the first aspect a study was carried out in 246 patients aged between 11 and 18 years. In 48 of the subjects (19.51%) there was loss of the first permanent molar tooth, 26 had lost one tooth, and 22 had lost two teeth. Occluding changes were more marked when the lower molar teeth were lacking. With regard to the second aspect the authors present several cases of anomalies of the dentomaxillary apparatus with distal occlusion, solved in the Begg technique. PMID- 2101269 TI - [Possibilities for remineralization in the incipient decay of the enamel]. AB - Admitting the fact that dental decay is the result of an imbalance between the process of demineralization and that of remineralization, one of the main problems of odontology remains the increase of mineralization in the dental enamel in the post-eruptive maturation stage, and the remineralization of the incipient dental decay lesions. The author reviews the main aspects related to remineralization of the incipient decay which occurs in the dental enamel, as well as the possibilities of stimulation of remineralization with the aid of various agents, or by the use of certain obturation materials, of which certain types of glass ionomeric cements are very promising. PMID- 2101270 TI - [Data on the epidemiology of dental decay in children aged between 6 and 12 years in the city of Cluj]. AB - The authors have studied two groups of children from the City of Cluj. The first lot included 1212 children aged 6-7 years, and the second one included 616 children aged 12-13 years. The study consisted in an evaluation of the status of definitive molar teeth in the period which followed the eruption. The frequency of decay was 47.62% for the first molar tooth, and of 37.12% for the second molar. The intensity index was 22.45% and 11.10% respectively. Six years after the eruption the frequency of decay in the first molar tooth was 85.23%, and the intensity was 56.58%. PMID- 2101271 TI - [Evaluation of morbidity through dental decay in students by school stomatologic monitoring]. AB - Starting from the fact that stomatologic dispensarization in schools is the best method for evaluating morbidity by bucco-dental disorders in students, the authors present the results of a longitudinal study which consisted in the permanent monitoring of 48 students for a period of 8 years (1980-1988). The children were from the I-st to the VIII-th class. It is stressed that the most relevant indexes of morbidity are those of incidence (for the evaluation of the present potential of developing a disorder), and that of severity (for the assessment of the morbidity status). The authors intend to take up again this study, with the same methodology, in a group of students to which a local fluorination procedure was applied from the I-st scholar cycle. PMID- 2101272 TI - [Frequency of tooth loss in children and young subjects]. AB - The frequency of edentation was evaluated in groups of children and young subjects aged between 7 and 18 years. The values obtained for this indicator have focused the attention on the type of organization and the quality of the curative assistance. Models for the processing of clinical data, as well as a comparison of the existing situation in the growth period with that of the adults has led to the establishment of conclusions concerning practical measures for the organization of the specialized assistance to children and young subjects. PMID- 2101273 TI - [Possibilities for orthodontic treatment in adults]. AB - Following a discussion on the controversial opinions concerning the orthodontial treatment in adults, as well as on the fact that in many cases the orthodontial treatments in adults are much shorter than in children, the authors present data on eight cases reflecting the possibilities of orthodontial therapy in adults. The authors stress the necessity that the orthodontist should recognize the limitations of such therapy in adults, increasing in this way the possibilities for a successful therapy. PMID- 2101274 TI - [Estimating some prospective of certain epidemiological, clinical and paraclinical investigations aiming at discovering the etiopathogenesis of the painful dysfunctional meniscus-condyle syndrome of temporo- mandibular joint for prophylaxis and individualized treatment]. PMID- 2101276 TI - [The role of health education in collectivities of children]. PMID- 2101275 TI - [Pulp prophylaxis by "Dentiform" biological paste for direct covering of the dent of pulp]. PMID- 2101277 TI - Canadian cancer statistics 1990. AB - In 1990, an estimated 104,000 new cases of cancer (excluding non-melanoma skin cancer) will be diagnosed in Canada. The estimated number of deaths due to cancer in that same year will total 54,500. Just over one in three Canadians can expect to develop some form of cancer during their lifetime, and one in four men and one in five women will die from this disease. Almost 10% of women will develop breast cancer, while close to 8% of men will develop lung cancer. In 1990, lung cancer alone is expected to account for 17,300 newly diagnosed cancers (16.6% of the total), and 14,200 cancer deaths (26% of the total). Cancer will also take its toll as the fourth leading cause of death in children. This article explores additional statistics, trends in cancer incidence and mortality since 1970, cancer survival rates, and cancer mortality by income level. This article is based on material prepared by Statistics Canada for inclusion in Canadian Cancer Statistics 1990 (1), and developed in collaboration with the Canadian Cancer Society, Health and Welfare Canada, and provincial and territorial cancer registries. PMID- 2101278 TI - Key health indicators database. AB - A new database developed by the Canadian Centre for Health Information (CCHI) contains 40 key health indicators and lets users select a range of disaggregations, categories and variables. The database can be accessed through CANSIM, Statistics Canada's electronic database and retrieval system, or through a package for personal computers. This package includes the database on diskettes, as well as software for retrieving and manipulating data and for producing graphics. A data dictionary, a user's guide and tables and graphs that highlight aspects of each indicator are also included. PMID- 2101279 TI - Canadian Farm Operator Study: methodology. AB - A mortality study of about 326,000 Canadian male farm operators enumerated in the 1971 Census of Agriculture is being conducted by Health and Welfare Canada in collaboration with Statistics Canada. The study examines the mortality patterns of farm operators in relation to farm practices and a variety of socio demographic variables. The prime concern is the association between pesticide use and certain cancers suggested in previous studies of farmers. This article describes the methodology used to create the study cohort and the analysis files. Highlights of the preliminary results from this study for Saskatchewan are also presented. Results for other regions are forthcoming. Among the Saskatchewan cohort of farm operators, 94% of deaths occurred within the province. The average age at death was 67.9 years and the average length of survival from 1971 was 13.9 years. Although the cohort as a whole had no excess mortality for any specific cause of death--including non-Hodgkin's lymphoma--significant dose-response relationships were noted between risk of non-Hodgkin's lymphoma and acres sprayed with herbicides in 1970, as well as with dollars spent in 1970 on fuel and oil for farm purposes (1). PMID- 2101280 TI - A standard data collection-package for medical follow-up studies. AB - A standard method of collecting identifying data for medical follow-up studies has been developed by Statistics Canada. By helping improve health record keeping, this method has the potential to make it easier to track populations exposed to potentially hazardous agents through lifestyle, work, environmental factors, ecological disasters, or medical treatments. The data collection package, which has been reviewed by expert groups and pilot tested, can reduce costs, save time and result in more comparable data. The package guides the user in developing an easily maintained and accessed database using either the Data Collection Package handbook or the personal computer package option. Part I of this article gives an overview of the new data collection package and how it can be used. Part II gives the background and methodological notes on its development. PMID- 2101281 TI - Addendum. Coronary artery bypass surgery in Canada. Health reports. Vol. 2, no. 1, pp. 9-26, July 1990. PMID- 2101282 TI - Preliminary annual hospital statistics 1988-89. PMID- 2101283 TI - Residential care facilities 1987-88. PMID- 2101284 TI - Cumulative quarterly hospital statistics. April 1, 1989-September 30, 1989. PMID- 2101285 TI - Canadian cardiovascular disease mortality: first generation immigrants versus Canadian born. AB - Cardiovascular disease (CVD) is the major cause of death in Canada, as it is in most industrialized countries. Studies have shown that CVD mortality rates vary among ethnic groups. Since about one in six Canadian residents is a first generation immigrant, it is important to consider ethnic background when interpreting Canadian health statistics or planning health services. Overall, lower CVD mortality rates were found for first generation Canadians from Latin America, China and South Asia; higher rates are indicated for those from Scandinavia and Africa. The rates for North America are similar to those found for Eastern and Western Europe. Between two five-year time periods (1969-73 and 1984-88), CVD mortality rates generally were found to decrease, except for immigrants from Africa (age 35+). The rates were consistently higher for males than for females. PMID- 2101286 TI - Therapeutic abortions, Canada, 1970-1988. AB - A total of 66,251 therapeutic abortions were performed in hospitals in Canada in 1988, an increase of 4.1% from the 63,662 performed in 1987. The abortion rate per 1,000 women 15-44 years was 10.6% in 1988, up from 10.2% in 1987. The number of therapeutic abortions performed annually peaked at 66,319 in 1982. The abortion rate peaked at 11.6% in 1979. Looking at marital status at the time of abortion in 1988, 67% of the women were single, 22% were married and 11% were widowed, divorced, separated, or living common law. About 22% of the women were under 20 years of age, 54.4% were between 20-29 years, 21.5% were between 30-39 years and 2.2% were over 39 years of age. At the time of pregnancy termination, the gestation period was under 13 weeks for 89.6% of abortion cases. The gestation period was 13 weeks or more for 10.4% of abortion cases. The trend towards abortions performed in the early stages of pregnancy may be one of the reasons for a 50% drop in the abortion complication rate to 1.6% of abortions in 1988 from 3.2% of abortions in 1975. PMID- 2101287 TI - List of residential care facilities, 1989. PMID- 2101288 TI - Nursing in Canada. Registered nurses--1989. PMID- 2101290 TI - Crohn's disease and ulcerative colitis: morbidity and mortality. AB - This study analyzes hospital discharges and deaths from 1971 to 1986 for patients with inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. The data are based on hospital morbidity and mortality statistics provided to Statistics Canada by the provinces. For Crohn's disease, age-standardized rates per 100,000 population for hospital discharges increased by 148% for males and by 192% for females over the study period. In 1986, the rate for females was 48% higher than the rate for males. For both males and females, age-specific discharge rates were highest in the 20-24 age group. For ulcerative colitis, male age-standardized discharge rates decreased by 17% from 1971 to 1977, and then increased by 41% from 1977 to 1986. For females, the rates decreased by 18% from 1971 to 1976, then remained fairly stable from 1976 to 1986. Male and female discharge rates were similar over the study period. For females, rates were highest in the 20-34 age groups; for males, they were highest in the 65 and older age groups. In 1971, rates for both types of IBD were almost the same, but by the end of the study period the rate per 100,000 population for Crohn's disease was 34 for females and 23 for males, while for ulcerative colitis the rates were 13 for females and 14 for males. During the 16-year study period, cause of death data showed 556 deaths directly attributed to Crohn's disease and 761 deaths attributed to ulcerative colitis. The under 45 age group accounted for 25% of deaths due to Crohn's disease and for 17% of deaths due to ulcerative colitis. The time trends for IBD hospital discharge rates in Canada closely parallel the findings of hospital discharge rates in the United States and England-Wales. A comparison with epidemiological population surveys strongly suggests that increased discharge rates are due mostly to increases in incidence and prevalence of IBD in the general population. PMID- 2101289 TI - Acute myocardial infarction. A feasibility study using record-linkage of routinely collected health information to create a two-year patient profile. Manitoba, 1984-85 and 1985-86. AB - Manitoba's hospital separations and physician medical files were linked for the fiscal years 1984-85 and 1985-86. The result was a study file consisting of records for 5,293 males and 3,143 females, who, during this period, suffered an Acute Myocardial Infarction (AMI), commonly called a heart attack. Merging the two types of files created a comprehensive data base for these AMI victims. The Manitoba age-sex standardized AMI rate was 38.0 per 10,000 population. Age specific rates were higher for males than for females for all age groups. Hospitalized cases accounted for 7,201 individuals or 85.4% of AMI victims. Age sex standardized rates of hospitalization per 10,000 population ranged from 27.1 in the Central region to 36.0 in the Westman region. The Manitoba age-specific rates of hospitalization for males in the 35-54 and 55-64 age groups were about three times the female rates for the same age groups. One quarter of AMI hospitalized victims died in hospital. The Manitoba age-specific death rates for males in the 35-54, 55-64 and 65-74 age groups were double the rates for females in the same age groups. Of the 8,436 AMI victims under study, 86.4% had at least one other concurrent medical condition such as angina, other forms of ischemic heart disease, diabetes, or hypertension. Of AMI victims, 93.8% underwent at least one of the following procedures: coronary artery bypass surgery, angiogram, electrocardiogram, cardiac catheterization, arteriography, or blood cholesterol testing. A higher percentage of procedures was performed on males than on females. PMID- 2101291 TI - Life expectancy in Canada--an overview. AB - At 73 years for men and more than 80 years for women, Canada's life expectancy at birth compares favourably with other developed countries; Japan currently leads the world with 75.6 years for men and 81.4 years for women. In 1920-1922, fewer than six out of ten Canadians could expect to survive to their 65th birthday; by 1985-1987, this had risen to eight out of ten. At the oldest ages, the increases in survival are even more striking. In 1920-1922, just over one in ten Canadians could expect to reach their 85th birthday; by 1985-1987, this had increased to more than three out of ten. Since the 1920s, life expectancy has been higher in the Western provinces and lower in Atlantic Canada and Quebec. In 1950-1952, for example, a person born in Saskatchewan could expect to live four years longer than a person born in Quebec. By 1985-1987, this difference had been reduced to just over one year. Women have made much greater gains in life expectancy than men. In 1920-1922, women had an advantage in life expectancy over men of less than two years; by 1970-1972, this had more than tripled to seven years. Married men and women have a distinct advantage in longevity over other marital status categories. Married men may expect to live over eight years longer than never married men, and more than ten years longer than widowed men. Married women can expect to live three years longer than never-married women, and four years longer than women who are either divorced or widowed. As of 1986, a boy born in highest income quintile area in urban Canada can expect to live almost six years longer than a boy born in a lowest-income quintile area. For girls, the difference is almost two years. However, this socio-economic differential narrowed from 1971 to 1986. PMID- 2101292 TI - Marriages, Canada and the Provinces, 1989. PMID- 2101293 TI - Profile of nursing education programs. PMID- 2101294 TI - The prevalence and management of dementia and other psychiatric disorders in nursing homes. AB - The prevalence of psychiatric disorders among new admissions to nursing homes is unknown. Such data are needed to estimate the psychiatric needs of this population. We report the prevalence of specific psychiatric disorders in 454 consecutive new nursing home admissions who were evaluated by psychiatrists and diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Eighty percent had a psychiatric disorder. The commonest were dementia syndromes (67.4%) and affective disorders (10%). Also, 40% of demented patients had additional psychiatric syndromes such as delusions or depression, and these patients constituted a distinct subgroup that predicted frequent use of restraints and neuroleptics, and the greatest consumption of nursing time. These data demonstrate that the majority of nursing home residents have psychiatric disorders on admission, and that their management is often quite restrictive. Research is now needed to determine the best methods of treatment for nursing home patients with mental disorders. PMID- 2101295 TI - Behavioral abnormalities and psychiatric symptoms in Alzheimer's disease: preliminary findings. AB - Behavioral abnormalities and psychiatric symptoms were assessed in 178 patients diagnosed as having Alzheimer's disease by NINCDS/ADRDA criteria. The subjects were selected from a defined catchment area and therefore were representative of a group of patients with Alzheimer's disease of varying severity. Auditory hallucinations were found in 10%, visual hallucinations in 13%, and delusions in 16%. Symptoms suggestive of depression were reported by 39% of the patients and features of depression observed in 25%. Twenty percent were aggressive, and 7% were sexually disinhibited. Nineteen percent exhibited excessive walking behavior and 10% binge eating. Nearly 50% of the sample were incontinent. Patients in the hospital were more often aggressive, incontinent, and seemingly less depressed. Patients with severe dementia displayed excessive walking behavior, were more likely to be incontinent, and reported less depressive symptoms than those with moderate or mild dementia. PMID- 2101296 TI - A quantitative study of intracranial calcification in dementia of the Alzheimer type. AB - Abnormalities in calcium homeostasis have been reported in Alzheimer's disease (AD) and in the neurofibrillary tangle disorders of amyotrophic lateral sclerosis and parkinsonism-dementia occurring in the Pacific. In order to more fully evaluate calcium physiology in AD, we analyzed the size of pineal and choroid plexus calcifications, using X-ray computed tomography, in 23 patients with probable AD and 18 healthy age-matched control subjects. The area occupied by calcification was measured from hard copies of the data by two independent observers who were blind to the diagnosis. There were no differences in the areas occupied by pineal or choroid plexus calcifications between the two groups. These data suggest that AD is not accompanied by alternations in intracranial calcium deposition in pineal gland or choroid plexus. PMID- 2101297 TI - Coexisting depression and dementia in a community survey of the elderly. AB - We report here on the coexistence of dementia and depression in a community population aged 75 years and older. Complete information about mood and cognition was available for 286 cognitively intact subjects selected for assessment because of their low scores on the Mini-Mental State, and for 158 mildly and moderately demented subjects. Severely demented subjects, who were incapable of providing information, were excluded. Five percent (8/158) of demented subjects also fulfilled criteria for major depressive disorder Diagnostic and Statistical Manual of Mental Disorders, third edition (DSM-III) compared with 9% (27/286) of cognitively intact subjects. No substantial differences existed in the symptoms reported by demented depressives and nondemented depressives, but subjects who suffered from both disorders were so markedly apathetic that their depression might easily have been overlooked had specific enquiries not been made. Depression was particularly associated with dementia secondary to multi-infarct and Parkinson's disease. When reviewed one year later, 2 of the 18 surviving depressed, nondemented subjects showed evidence of dementia. Both presented unusual diagnostic difficulties, however, and no evidence emerged that large numbers of elderly people will be misclassified in community surveys that include a mental state examination, cognitive testing, and an informant interview. PMID- 2101298 TI - Aging and alcohol use disorders: diagnostic issues in the elderly. AB - Alcohol use and use disorders in older people tend to be hidden and ignored by clinicians and scholars. Resulting misinformation about elderly alcohol problems can be found in such fundamental works as the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Yet, an extensive literature about the nature of geriatric alcohol problems has developed recently. This article reviews that literature, comments on current research at several North American centers, and offers some new information from the author's study of more than 300 older male alcoholics. Many findings remain to be replicated and further verified. Nonetheless, several coherent strands of information seem to be well substantiated: (a) problem drinking in the elderly constitutes a public health problem of moderate proportion, especially in men; (b) most signs predict increasing problem drinking in coming generations of elderly women and men; (c) many cases of geriatric alcoholism have late onset; (d) many geriatric cases are not properly identified; and (e) present screening and diagnostic methods for alcohol use disorders lack adequate validation for older persons. PMID- 2101299 TI - Psychogeriatrics in the 1990s. PMID- 2101300 TI - Development of psychogeriatric medicine in Sweden. PMID- 2101301 TI - Factor analysis and preliminary validation of the mini-mental state examination from a longitudinal perspective. AB - The Mini-Mental State Examination (MMSE) is a commonly used instrument for assessing mental impairment. Previous proposals for its underlying structure have focused on scores obtained from a single administration of the test. Because the MMSE is widely used in longitudinal studies, we examined the pattern of relations among the rates of chance of the items. Data were obtained from 63 subjects for 1.5 years or more. The relations among the rates of change of the MMSE items were described by a five-factor solution that accounted for 75% of the variance and comprised factors pertaining to orientation and concentration, obeying commands, learning and repetition, language, and recall. This was in contrast to the structure of the scores obtained from a single administration of the MMSE, which was best described by a two-factor solution. In order to provide a clinical validation, factor scores derived from the MMSE factors were used to predict scores on the Memory and Behavior Problems Checklist and the Brief Cognitive Rating Scale. PMID- 2101302 TI - Toward a molecular etiology of Alzheimer's disease. AB - Recent progress in the biochemical characterization of Alzheimer's disease (AD) neuropathology has led to the proposal of three hypotheses for the molecular etiology of AD. One focuses on calcium-activated neutral proteases or calpains (Nixon, 1989). Another focuses on protein phosphorylation (Saitoh & Iimoto, 1989). A third is centered on altered phospholipid metabolism (Pettegrew, 1989). Interestingly, all three hypotheses are mutually compatible, involving closely interlocking biochemical systems. Disturbances in any one of these systems might result in the same type of neuropathology, consistent with suggestions that AD could have multiple etiologies. Future investigations of the function and interrelation of these systems in the central nervous system in general and at the synaptic junction in particular are likely to have significant bearing on our understanding of AD. PMID- 2101303 TI - Low diagnostic yield in a memory disorders clinic. AB - A review of the first 144 patients to attend a Memory Disorders Clinic found not one case of treatable dementia. The use of a routine comprehensive battery of investigations was not supported: however, computerized tomographic brain scans and electroencephalograms were moderately useful in diagnosing dementia. Clinical features and historical data did not discriminate early- from late-onset Alzheimer's disease or Alzheimer's disease from multi-infarct dementia. PMID- 2101304 TI - Geriatric psychiatry consultations in a university hospital. AB - A review was conducted of the records of 147 patients above the age of 60 in a 350-bed general university hospital for whom a request for consultations was made over a two-year period by a geriatric psychiatry division in a department of psychiatry. Findings were compared with those obtained by Mainprize and Rodin and by Ruskin. Most referrals in the present study were from internal medicine as they were in the other two studies. The principal reason for referrals in this and in Mainprize and Rodin's study was depression (48% and 37%, respectively) but not in Ruskin's study (10%). The primary DSM-III-R diagnoses of the referred patients in this study were affective disorder (27%), adjustment disorders (26%), and dementia (22%). Affective disorder was also the most frequent diagnosis in Ruskin's study. Psychotropic medication was the most frequently cited recommendation in all three studies. PMID- 2101305 TI - Status of psychogeriatrics in The Netherlands. PMID- 2101306 TI - Psychogeriatrics in Israel--present and future. PMID- 2101307 TI - The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients. PMID- 2101308 TI - Nucleotide sequence of two soybean ENOD2 early nodulin genes encoding Ngm-75. PMID- 2101309 TI - The four members of the gene family encoding the Arabidopsis thaliana translation elongation factor EF-1 alpha are actively transcribed. PMID- 2101310 TI - Expression of a rice glutelin promoter in transgenic tobacco. AB - A chimeric gene consisting of the 5' flanking sequences of a rice glutelin gene (Gt3) linked to the chloramphenicol acetyltransferase (CAT) coding segment was introduced into tobacco via Agrobacterium tumefaciens-mediated transformation. CAT enzyme activity could be detected in extracts from seeds as early as 8 days after flowering and obtained a maximum level at 16 days after flowering, the onset of overall protein accumulation. Significant expression of CAT activity in non-seed tissues occurred in some, but not all plants, suggesting possible chromosome position effects on non-seed tissue expression. A positive correlation was observed between expression levels in seeds and gene copy numbers. PMID- 2101311 TI - Systemically wound-responsive genes in poplar trees encode proteins similar to sweet potato sporamins and legume Kunitz trypsin inhibitors. AB - When the lower leaves of hybrid poplar trees are mechanically wounded, several novel mRNAs accumulate in the unwounded upper leaves (Parsons TJ, Bradshaw HD, Gordon MP: Systemic accumulation of specific mRNAs in response to wounding in poplar trees, Proc Natl Acad Sci USA, in press). A partial cDNA clone corresponding to a transcript from the wound-responsive gene designated win 3 (wound-inducible) has been cloned by differential hybridization to 32P-labelled cDNA from the leaves of wounded trees. Northern blots show a large accumulation of win 3 transcripts in the unwounded leaves of wounded trees. Southern blot analysis of poplar DNA suggests that win 3 is a member of a multigene family. The nucleotide sequences of several win 3 cDNA clones have been determined, indicating that at least three win 3 gene family members are transcribed. A genomic clone of a win 3 gene family member has been isolated and a 1.5 kb Hind III fragment containing the predicted protein-coding and 5' upstream regions has been sequenced. The putative win 3 gene product is similar to the major soluble proteins of sweet potato tubers, sporamin A and sporamin B. Both Win3 and the sporamins share significant amino acid sequence identity with Kunitz-type trypsin inhibitors from legume seeds. The Kunitz family of proteinase inhibitors thus joints three other proteinase inhibitor families which are systemically responsive to wounding. PMID- 2101312 TI - Localized transient expression of GUS in leaf discs following cocultivation with Agrobacterium. AB - A chimaeric gene has been constructed that expresses beta-D-glucuronidase (GUS) in transformed plant tissues, but not in bacterial cells. This gene has proved extremely useful for monitoring transformation during the period immediately following gene transfer from Agrobacterium tumefaciens. GUS expression was detectable 2 days after inoculation, peaked at 3-4 days and then declined; if selection was imposed expression increased again after 10-14 days. The extent of transient expression after 4 days correlated well with stable integration as measured by kanamycin resistance, hormone independence, and gall formation. Histochemical staining of inoculated leaf discs confirmed the transient peak of GUS expression 3-4 days after inoculation. The most surprising result was that the blue staining was concentrated in localized zones on the circumference of the disc; within these zones, essentially all the cells appeared to be expressing GUS. We suggest that the frequency of gene transfer from Agrobacterium is extremely high within localized regions of leaf explants, but that the frequency of stable integration is several orders of magnitude lower. PMID- 2101313 TI - Methylated and undermethylated rDNA repeats are interspersed at random in two higher plant species. AB - The organization of methylated rDNA repeats of radish and pea is described and it is shown that methylated repeats and non-methylated repeats are interspersed one with another. Methylated arrays are not much longer than 100 kb, or about 10 repeat units in length. PMID- 2101314 TI - Purification and N-terminal sequencing of style glycoproteins associated with self-incompatibility in Petunia hybrida. AB - We report isolation and N-terminal amino acid sequencing of three style glycoproteins, which segregate with three S (self-incompatibility) alleles of Petunia hybrida. The S-glycoproteins were expressed mainly in the upper part of the pistil and showed an increasing concentration during flower development. The glycoproteins were purified by a combination of ConA-Sepharose and cation exchange fast protein liquid chromatography. The amount of S-glycoproteins recovered from style extracts varied from 0.5 to 1.6 micrograms per style, which was 40-60% of the amount recovered by a simplified analytical method. N-terminal amino acid sequences of S1-, S2- and S3-glycoprotein showed homology within the fifteen amino terminal residues. These amino acid sequences were compared with the previously published sequences of S-glycoproteins from Nicotiana alata and Lycopersicon peruvianum. PMID- 2101315 TI - The significance of phenotyping leukemias using monoclonal antibodies. AB - 1. Acute leukemias have been defined as major types of lymphoblastic and myeloblastic leukemias according to morphological and cytochemical criteria. 2. The technical improvements and standardization of immunofluorescence and immunocytology staining methods have provided new insights for classifying these disorders on the basis of monoclonal antibodies. 3. The scheme used to describe normal lymphoid and myeloid differentiation, when also used to describe their malignant counterparts, provides a well-established model for the immunological classification of acute leukemias. 4. In this review article, we suggest some guidelines for performing a series of cytochemical reactions using immunological markers to ensure a reliable diagnosis of acute leukemia. PMID- 2101316 TI - A statistical treatment for solution of a family of simultaneous equations derived from enzyme inhibition studies. AB - 1. A technique of simultaneous regression of a family of lines with any common intercept is described for the treatment of enzyme inhibition data. The method is iterative and is based on minimization of a weighted sum of squares of all residues. 2. The weighting procedure may be varied according to experimental design; the simultaneous regression treatment provides the crossing point of all lines, linear and angular coefficients, as well as estimates of the precision of fitted parameters. 3. There are no restrictions as to location of crossing points. The method can be applied to all known transformed functions, properly weighted, used in enzyme studies that result in straight lines. It is rather simple to use by non-kineticists and would be useful in preliminary diagnosis of inhibition types, prior to the application of nonlinear techniques which require knowledge of the model. PMID- 2101317 TI - Metabolism of dipeptides by isolated and perfused nonfiltering kidneys. AB - Renal metabolism of Glycyl-glycine (Gly-gly), Glycyl-proline (Gly-pro) and Prolyl glycine (Pro-gly) was studied in the non-filtering, isolated perfused rat kidney. Gly-gly is metabolized by more than 90% after 120 min of perfusion. Gly-pro is more resistant to degradation and about 75% of the original peptide can be found intact in the perfusate at the end of perfusion. For Pro-gly, only 25% remains intact at the end of the experiment. Glycine was also monitored as another marker for dipeptide degradation and its production increased throughout the perfusion time. In some experiments we also determined the production of proline. We conclude from these experiments that the basolateral membrane, or perhaps the kidney blood vessels, possess an efficient apparatus for the hydrolysis of Gly gly and Pro-gly. This mechanism is less efficient in the case of Gly-pro. This confirms an earlier hypothesis that dipeptide metabolism does not occur solely in the brush-border membranes. PMID- 2101318 TI - Binding of the anti-inflammatory drug niflumic acid to bovine serum albumin. AB - Binding of the anti-inflammatory drug niflumic acid to serum albumin was measured by equilibrium dialysis and the dissociation constants were determined. The maximal binding capacity was 36 mol niflumic acid per mol albumin. Most of the binding sites were of low affinity, only six having dissociation constants below 1 mM. At the plasma concentrations most frequently used in experimental work, the high affinity sites account for more than 99% of the albumin-bound niflumic acid. PMID- 2101319 TI - Generation of cell lines to study the role played by oncogenes and anti-oncogenes in cell proliferation control. AB - We report the generation of stable transfectant cell lines by DNA-mediated transfection that overexpress viral and/or cellular oncogenes. Expression of heterologous genes (FBJ- and FBR-v-fos, polyoma large and middle T) was confirmed by Northern hybridization, immunofluorescence and immunoprecipitation. We also describe the isolation of two retinoblastoma cell lines from human tumors. Neuronal and glial markers were used to confirm the origin of these cell lines. Oncogene transfectant and retinoblastoma cell lines will be used to assess Rb expression and the possible role of its gene product in cell proliferation control and neoplasia. PMID- 2101320 TI - The use of a new non-verbal test in the evaluation of recent memory. AB - A test for recent memory was developed using non-verbal material. The present report describes a series of experiments conducted to evaluate its reproducibility and the influences of changes in the interval between acquisition and retrieval, and age and level of instruction, and its sensitivity to the integrity of memory function. A total of 114 subjects participated in 5 experiments. The test of recent memory is reproducible over a period of at least 5 months and can be used with training-testing intervals of 24 to 48 h. The performance of the test is affected by age and level of instruction. Moreover, the memory test is sensitive to differences in the integrity of memory function. Thus, the memory test developed in this study may be used to evaluate the effects of behavioral and/or pharmacological manipulations on recent memory in homogeneous groups of subjects. PMID- 2101321 TI - Antimitotic effect of an extract of the sea anemone Bunodosoma caissarum on sea urchin egg development. AB - A methanolic extract of the sea anemone Bunodosoma caissarum has an antimitotic effect on sea urchin egg development. The extract produces a dose-dependent inhibition of cell cleavage. When the extract is added together with sperm to unfertilized sea urchin eggs, the ED50 is 0.60 +/- 0.03 mg/ml (mean +/- SEM). When added shortly after fertilization, the extract produces the same kind of progressive inhibition but with an ED50 of 0.98 +/- 0.16 mg/ml. In the first case, detachment of the vitelline layer is inhibited whereas in the second case the extract inhibits cleavage even when the membrane is present. PMID- 2101322 TI - Central glucoregulation in the pigeon Columba livia. Effects of intraventricular injections of carbachol and catecholamines on blood glucose concentration. AB - The effect of chemical stimulation of the central nervous system on glucoregulation was studied in pigeons (Columba livia). Adrenaline (30 nmol), noradrenaline (30 or 80 nmol) and carbachol (27 nmol) were injected in 1 microliter NaCl directly into the lateral ventricle and changes in blood glucose concentration were measured. The intraventricular injection of adrenaline resulted in rapid hyperglycemia, whereas the injection of either carbachol or noradrenaline into the lateral ventricle did not cause any significant changes in blood glucose concentration. These results suggest that adrenaline-containing neurons may be involved in central mechanisms controlling blood glucose concentration in the pigeon. PMID- 2101323 TI - Histochemical and histological analysis of the Leydig cells of cats treated with a supraphysiological dose of LH-RH analog. AB - An LH-RH analog (des-Gly10,[D-Trp6]-LH-RH ethylamide, LH-RH A) was administered to adult male cats for 67 days (20 micrograms/kg, sc) in order to study its inhibitory effects on the structure of Leydig cells, as determined by histological and histochemical-morphometric techniques. Histological examination showed that LH-RH A promotes a decrease in the volume of the interstitial tissue. In addition, Leydig cell nuclei exhibited marked structural alterations. Morphometric analyses utilizing histochemistry of the enzyme 3-beta hydroxysteroid dehydrogenase (3-beta-HOST-D) as a marker of Leydig cells also demonstrated a significant decrease of the relative volume occupied by the Leydig cells in the testis. PMID- 2101324 TI - Exogenous ganglioside stimulation of axonal regeneration after nerve transection and entubulation repair. AB - Adult male mice received sciatic nerve transection at the midthigh level and both nerve stumps were sutured into a polyethylene tube (PT) to bridge a nerve gap of 4 mm. The tubes were implanted either empty, or filled with collagen alone or in combination with gangliosides (GM1, GD1a, GD1b and GT1b). Following a survival time of 6 weeks, the PT with the regenerating nerve cables were processed for plastic embedding, and morphometric measurements were made on myelinated and unmyelinated axons. The data suggest that local application of exogenous gangliosides causes a stimulation of axonal sprouting in vivo with no effect on the rate of axonal maturation. PMID- 2101325 TI - Effect of amygdaloid kindled seizures during pregnancy on neonatal brain biogenic amines. AB - The effects of amygdaloid kindled seizures during pregnancy on the concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5HT) and of their respective metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NMN), homovanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5HIAA), have been studied in the cerebral cortex, brain stem and cerebellum of rat offspring at birth. The levels of DA and NE were increased and those of HVA and MHPG were not modified in the cortex. The levels of DA, NE, 5HT, MHPG and 5HIAA were increased in the cerebellum. The brain stem presented a decrease in DA and 5HT levels, but increased MHPG and HVA levels. It is suggested that, in order to investigate possible changes in the biogenic amine levels on the postnatal period, carefully planned prospective studies are needed. PMID- 2101326 TI - Metabolic adjustment induced by exposure to elevated ambient temperature is impaired in rats bearing lesions in the preoptic area. AB - Metabolic adjustment was studied in rats with bilateral electrolytic lesions in the preoptic area which were exposed to heat (34 degrees C) and to normal temperature (25 degrees C) for 60 days. The metabolic rate measured at neutral temperature (29 degrees C) in preoptic-lesioned rats living at 25 degrees or 34 degrees C was reduced to 80% the rate of sham-operated controls. The increase in metabolic rate induced by heat (30 min at 34 degrees or 37 degrees C) in preoptic lesioned rats, living at 25 degrees C, was markedly reduced to 10% the rate of sham-operated controls living at 25 degrees C. In preoptic-lesioned rats, the increased metabolic rate induced by heat exposure (34 degrees or 37 degrees C) was impaired, regardless of the living ambient temperature (25 degrees or 34 degrees C) of the animal. These data demonstrate the participation of the preoptic area in heat-induced increased oxygen consumption and provide additional evidence for its role in the integration of thermal inputs with energy-linked metabolic processes. PMID- 2101327 TI - Kinetics of pleural exudation and cellular alterations induced by antigen in actively sensitized rats. AB - This study was undertaken to characterize the different phases of the allergic pleurisy induced by ovalbumin in actively sensitized rats. The reaction was triggered by the intrathoracic injection of ovalbumin (12 micrograms/cavity) into animals sensitized 14 days before. The challenge caused, at 30 min, a drastic mast cell degranulation and exudation which peaked within 4 h. At this time, an intense pleural leucocyte recruitment also occurred, accounted for by an increase in the mononuclear cell counts and by a predominant influx of neutrophils. After 24 h, the mast cell counts started to recover, accompanied by a long-lasting (96 h) accumulation of pleural eosinophils. Forty-eight hours later, the exudation and neutrophils were at basal levels, whereas mast cell counts increased progressively to reach control values at 120 h. This study describes the time course of the exudative and cellular alterations observed during pleural inflammation induced by low antigen concentrations. PMID- 2101328 TI - Specific responses to two unrelated antigens in mice made orally tolerant to one of them. AB - BDF1 and B10 mice, either normal or exclusively fed egg white diluted in water, were immunized with ovalbumin (OVA), sheep erythrocytes (SRBC) or OVA + SRBC. BDF1, but not B10, mice became tolerant to OVA and presented a 100% increase in the total number of immunoglobulin-secreting cells in the spleen. Immunization with OVA + SRBC markedly increased the response to OVA, except in tolerant BDF1 mice, and had no effect on the anti-SRBC PFC response, except in normal (non tolerant) BDF1 mice. PMID- 2101329 TI - Effects of chronic domperidone treatment on rat conditioned avoidance behavior. AB - The effects of chronic administration of domperidone (DOM), a peripherally acting anti-emetic and hyperprolactinemic D2-dopaminoceptor antagonist, on active and inhibitory conditioned behavior were tested on male and female rats. DOM (4 mg/kg) was injected ip daily either for 5 or 30 days. Although treatment for 5 days failed to affect experimental parameters, treatment for 30 days impaired the performance of active conditioned avoidance of female, but not male, rats. This effect was no longer observed 7 days after ending treatment. No effects of DOM treatment were observed on active conditioned avoidance of male rats or on inhibitory conditioned behavior of all rats. These data suggest that female rats are more susceptible to the hyperprolactinemic effects of DOM than male rats. However, an influence of estrous cycle interruption cannot be rejected. PMID- 2101330 TI - Inhibition of chlorpromazine-induced catalepsy by the 5-HT-1A ligands pindolol and buspirone in mice. AB - Neuroleptics such as chlorpromazine and haloperidol are capable of inducing catalepsy in rodents. Non-selective 5-hydroxytryptamine (5-HT) antagonists such as methysergide reduce the cataleptic effect of haloperidol. The present study was designed to evaluate the participation of 5-HT-1A receptors in chlorpromazine induced catalepsy in mice. Pindolol and buspirone, two putative 5-HT-1A receptor ligands, were used. Pretreatment with these drugs reduced the cataleptic effect of chlorpromazine. Clomipramine, a 5-HT neuronal uptake blocker, reversed the inhibitory effect of buspirone. Pretreatment with clomipramine alone caused a potentiation of neuroleptic-induced catalepsy. These results suggest that central 5-HT-1A receptors play an important role in neuroleptic-induced catalepsy in mice. PMID- 2101331 TI - Single dose toxicity study of beta-myrcene, a natural analgesic substance. AB - The present study was undertaken to provide data on acute toxicity of beta myrcene, a peripheral analgesic substance found in the essential oils of several plants. Although myrcene has long been used in perfumes and as a food additive, there is almost no information on its toxicological hazards. The acute oral toxicity of myrcene was low in rodents, with approximate lethal doses (ALD) of 5.06 g/kg body weight for mice and greater than 11.39 g/kg body weight for rats. Necropsy data did not reveal any relevant alteration in rats but histopathology findings in mice suggested that the liver and stomach may be target organs for myrcene toxicity after oral administration. Myrcene is highly irritant to the peritoneum, and deaths after intraperitoneal injection of this monoterpene in rats (ALD 5.06 g/kg body weight) and in mice (ALD 2.25 g/kg body weight) were probably due to drug-induced chemical peritonitis. PMID- 2101332 TI - The effect of age on the pressor response produced by common carotid artery occlusion in conscious rats. AB - The pressor responses to 60 s of common carotid artery occlusion were studied in conscious male rats of different ages. Compared to rats at the age of 2 months, the initial peak and the maintained response in 6- 12- and 18-month old rats were well preserved. In 1-month old rats, both components were significantly depressed but in 24-month old rats only the initial peak of the pressor response was markedly attenuated. These findings demonstrate that age is an important factor in the response to common carotid artery occlusion which is more marked for the initial peak than the maintained response. PMID- 2101333 TI - Effects of Walker 256 carcinoma on metabolic alterations during the evolution of pregnancy. AB - The control of pregnant cancer patients is difficult because it involves both mother and fetus, and the metabolic alterations in the cancer host induce a massive mobilization of nutrients diverted to the neoplastic cells. The purpose of the present study was to determine the evolution of the Walker 256 carcinoma in pregnant rats and its consequences on fetal development. The results showed that the tumors displayed a very rapid rate of growth and induced a reduction in fetal weights in the pregnant tumor-bearing rats. The tumor-bearing and pregnant tumor-bearing groups showed a decrease in blood glucose and total serum protein, suggesting an increase in energy utilization of these substrates and synthetic activity by the tumoral cells. An imbalance between protein synthesis and catabolism may occur in the tumor-bearing rats which may be related to the degree of nutritional depletion. PMID- 2101334 TI - The spatial arrangement of the semicircular canals of the pigeon. AB - The spatial orientation of the semicircular canals (SCC) was measured in the pigeon by fitting the best plane over 10 to 15 stereotaxically determined points to each canal. The vectors defining each canal plane are presented in the standard stereotaxic position and for free moving behavior, and the coplanarity or orthogonality of pairs of semicircular canals are discussed. PMID- 2101335 TI - Participation of nucleus raphe obscurus in the control of sympathetic activity in the anesthetized rat. AB - The medullary raphe nuclei are involved in the control of sympathetic activity during desynchronized sleep and in the modulation of nociceptive sensory inputs. To determine the participation of cholinergic and opiate mechanisms in the control of sympathetic activity, we microinjected eserine, morphine and naloxone into the nucleus raphe obscurus (NRO) of urethane-anesthetized rats. Arterial blood pressure (BP) and renal nerve activity (RN) were recorded. Eserine and morphine induced significant reductions of RN and BP, while naloxone had no effect. It is suggested that cholinergic and opiate mechanisms participate in the control of sympathetic activity by the NRO. PMID- 2101336 TI - Effect of dehydration on the increase of arterial pressure and renal electrolyte excretion produced by central cholinergic stimulation in rats. AB - Natriuresis, kaliuresis, diuresis, arterial pressure and heart rate were studied in rats following dehydration and cholinergic stimulation of the medial septal area (MSA). The increase in renal Na+ and K+ excretion produced by the injection of carbachol (2 nmol) into the MSA in normal hydrated rats was abolished in 48-h water-deprived rats. Urinary volume was also reduced. Cholinergic stimulation of the MSA produced a smaller increase in arterial pressure in 48-h water-deprived rats compared to normal hydrated animals. No change was observed in heart rate. These results show that hydration state is essential for the central cholinergic control of electrolyte excretion and increase in arterial pressure. PMID- 2101337 TI - [Biliary cystadenoma and cystadenocarcinoma]. AB - The authors present their experience with 5 biliary cystadenomas (BCA) and 1 cystadenocarcinoma (BCAC). BCA are rare but intriguing lesions of the liver for the possibility of the former to evolve into malignant lesion. Preoperative diagnosis is often difficult also at ultrasound and CT scan. The possibility of BCA and BCAC should be always ruled out in every cystic lesion of the liver. In every doubt lesion surgical exploration is indicated and at least a biopsy should be performed. The procedure of choice for BCA is radical resection, while palliative procedures may be justified only in poor risk patients. PMID- 2101338 TI - [The role of aluminum in carcinogenesis]. PMID- 2101339 TI - [Renal-colonic-cutaneous fistula secondary to xanthogranulomatous pyelonephritis]. AB - The appearance of intestinal fistulas secondary to kidney disease is a rare occurrence. Even rarer are complex fistulas involving several organs or systems [correction of apparati]. In this study, the authors report on a case of reno colo-cutaneous fistula which set in as a complication of xanthogranulomatous pyelonephritis. PMID- 2101340 TI - [Benign neoplasms of the small intestine]. AB - The authors report four cases of benign tumors of the small bowel (2 leiomyomas and 2 lipomas). After a short review of the literature, they put in evidence the relatively infrequent occurrence and the difficulties involved in early preoperative diagnosis. PMID- 2101341 TI - [Difficulties in interpreting a conspicuous retroperitoneal hematoma due to rupture of the inferior pancreatico-duodenal vessels at the onset of edematous type acute pancreatitis]. AB - The authors report on a case of conspicuous retroperitoneal haematoma with haemoperitoneum due to rupture of the lower pancreatico-duodenal vessels appearing at onset of an acute oedematous pancreatitis. After stressing the rarity of this event, the authors go on to discuss a number of aetiopathogenetic, diagnostic and therapeutic aspects. PMID- 2101342 TI - [Leiomyoma of the nipple (a case report and review of the literature)]. AB - The leiomyoma of the nipple is a very rare affection. No more than 20 cases are reported in the literature of the last 50 years. This neoplasm presents a difficult differential diagnosis with the remaining phlogistic and neoplastic breast diseases. We report a personal case with a review of the literature. PMID- 2101343 TI - [Rare locations of hydatidosis (a case with a mesocolic site)]. AB - The AA. describe a case of hydatic cyst in mesosigmoid probably original, which dispose an occlusion of the bowels. They take a beginning by this case, for to offer a revision of the literature and for to debate about the way of installation in peripheric site of Echinococcus in larval stage. PMID- 2101344 TI - [Major hepatectomies in liver neoplasms]. AB - The development of major hepatic resective surgery during the last 50 years is due to a better knowledge of both hepatic regenerative capacity and intraparenchymal vascular and biliary anatomy. Two approaches of major hepatic resection have been described: 1) primary hilar approach; 2) primary transparenchymal approach. The authors review the indications of major hepatic resections in the treatment of hepatic tumors and discuss the advantages and the disadvantages of primary hilar and primary transparenchymal approaches, reviewing the data from the literature and the experience gained at the Clinica Chirurgica of the University of Verona from 1970 to 1989 of 289 major hepatic resections. PMID- 2101345 TI - Fine needle aspiration cytology: utilization in pediatric pathology. AB - Fine needle aspiration can serve as the initial diagnostic modality for a wide variety of lesions within the pediatric age group. The utility of the technique depends on the clinical setting and histologic type of tumor under study. FNA is most valuable for staging and conformation of metastatic spread in small round cell malignancies. The use of aspiration cytology as the initial diagnostic procedure for these neoplasms is more controversial since this technique may deprive the clinician of valuable information (histologic subtype, oncogene status) now available only by examination of large tissue biopsies. Similarly, FNA can serve as a triage technique for the separation of patients harboring thyroid nodules or enlarged lymph nodes into operative candidates and non operative candidates. As cytopathologists become more familiar with the appearance of pediatric neoplasms, this diagnostic technique will become more widely used, reducing the need for operative intervention in the diagnosis of many benign and reactive lesions. PMID- 2101347 TI - Serological and molecular studies of HLA in insulin-dependent diabetes mellitus in Sardinia. AB - This study was carried out in Sardinia, an Italian region with a very high IDDM incidence. HLA class I and class II antigens were studied in 97 unrelated IDDM patients, 33 complete families with at least one affected member each, and 559 healthy controls. Molecular typing of the DQB1 alleles was carried out in 31 patients and 61 controls. The haplotypes were determined by family studies. The HLA-DR3, DQw2, and DR4 antigens were positively associated with IDDM. The DR3 antigen was nearly always associated to B18 and frequently carried by the extended haplotype A30 Cw5 B18 3F130 DR3 DQw2. The genotype analysis of the patients showed a strong increase of the DR3/DR4 heterozygotes with a relative risk higher than that of the DR3 and DR4 homozygotes. The DR2 antigen was negatively associated with IDDM in the central island districts but not in the southern districts. The DQB1 molecular analysis showed only three alleles in the patients: DQB1*0201 (75.8 per cent), DQB1*0302 (16.1 per cent), and DQB1*0502 (8.1 per cent). These alleles are non Asp 57, so it would seem that nearly if not all Sardinian IDDM patients are NA/NA homozygotes. The DQB1*0502 allele, extremely rare in other Caucasian populations, represents in Sardinia about 70 per cent of the HLA-DR2 haplotypes, contributing to the increase of the pool of IDDM susceptible genes. Moreover it is carried in 27 per cent of the DR2 positive individuals with the extended haplotype A2 Cw7 Bw58 3F31 DR2 DQw1.AZH. PMID- 2101346 TI - HLA-DRw15 is increased in frequency in Japanese scleroderma patients. AB - HLA-DRB allogenotypes were compared in 18 Japanese scleroderma patients and healthy Japanese controls. HLA-DRw15 was found to be significantly increased in frequency in the patient series compared to controls (chi 2 = 4.25, p less than 0.05, Yates' corrected); in DRw15 positive individuals the relative risk of developing scleroderma was 4.0. In Caucasoids DRw11 is significantly associated with scleroderma (Dunckley et al., 1989) and sequence data shows that DRw11 and DRw15 DRB molecules (together with DRw8 where the relative risk of developing scleroderma in Caucasoids is 2.1) share the same amino acid sequence at position 67-70 in the first domain. This would suggest that the DRB1 locus may well be the primary disease promoting locus in scleroderma. PMID- 2101348 TI - Characterisation of a short, highly repeated and centromerically localised DNA sequence in crested and marbled newts of the genus Triturus. AB - A 32-33 bp highly repeated DNA sequence, TkS1, has been isolated from genomic DNA of the newt Triturus karelini digested with the restriction endonucleases HaeIII or AluI. TkS1 is known to be localised in the centromeric heterochromatin of all the chromosomes in T. karelini and the related species T. cristatus. TkS1 has been shown to be present in varying amounts in the genomic DNA of a range of species of Triturus, including representatives of the two main subgenera Triturus and Palaeotriton. A programme of sequencing of monomers, dimers and trimers of TkS1 was carried out in order to determine the level of conservation of the sequence within and between species of Triturus. Altogether 204 monomer (32/33 bp) clones were made of TkS1 from three individuals of T. karelini, and one individual each of T. cristatus, T. carnifex, T. dobrogicus and T. marmoratus, all members of the subgenus Triturus and the cristatus species group. A number of dimer (64 bp) and trimer (96 bp) clones were also made from DNA of a single specimen of T. karelini digested with HaeIII or AluI. Three distinct types of TkS1 were identified in all species examined, except for T. marmoratus where only two of the types were found. The types were distinguished on the basis of certain recurring divergent patterns in monomers sequenced from T. karelini. Type 1 is mainly characterised by the presence of an AluI site at positions 24-27 and type 3 mainly by the presence of an additional base (C) at position 14. Type 2 normally lacks the AluI site and the C at position 14, as well as having a number of other distinguishing features. TkS1 and its three types have remained remarkably constant in sequence since before the divergence of T. marmoratus from other species in the cristatus species group, about 10 million years ago. Examination of all 204 monomer clones and comparison with consensus sequences for the three types shows less than 5% divergence at any one position in the sequence. There is good evidence from examination of dimer and trimer clones of TkS1 that the different types are intermingled with each other, and all three types are likely to be present on all chromosomes. Dimeric (64 bp) TkS1 clones constructed from AluI fragments of T. karelini DNA show evidence of a trimeric (96 bp) "supertype" with the pattern type 1-type 3-type 1 that is much more common than would be expected on a random basis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2101349 TI - Heterochromatin: junk or collectors item? PMID- 2101350 TI - The centromere specific histone CENP-A is selectively retained in discrete foci in mammalian sperm nuclei. AB - The 17 kDa human autoantigen designated CENP-A is a centromere specific histone. We show here that CENP-A is present in tissue of bovine origin, and that it is quantitatively retained in mature spermatozoa. This result is striking, as a prominent feature of spermatogenesis in mammals is the replacement of most somatic and testes specific histones with protamines. Indirect immunofluorescence studies further show that CENP-A is retained in sperm nuclei in discrete foci, rather than being dispersed throughout the sperm head. These observations suggest that CENP-A is a functionally important component of centromeres, and that pre existing CENP-A:DNA interactions are likely to be important in organizing the centromeres of the paternal genome during early embryogenesis. PMID- 2101352 TI - Neodymium: YAG laser therapy in aphakic pupillary block glaucoma and aphakic malignant (ciliovitreal block) glaucoma. AB - Aphakic pupillary block glaucoma and malignant glaucoma (ciliovitreal block) are severe complications of the intracapsular cataract extraction, presenting clinically as elevated intraocular pressure, persistent shallow anterior chamber and severe vitreal hernia. Six eyes (four women and two men) with aphakic pupillary block glaucoma and aphakic malignant glaucoma were resolved by Neodymium: YAG laser iridotomy and hyaloidotomy. The laser therapy resulted in immediate deepening of the anterior chamber and reducing of intraocular pressure. No side effect was observed. Neodymium: YAG laser iridotomy and hyaloidotomy may be more effective and simple than penetrating surgery in such cases. PMID- 2101351 TI - Identification of a soluble precursor complex essential for nuclear pore assembly in vitro. AB - We analysed the soluble form in which the nuclear pore complex protein p68 is stored in Xenopus laevis eggs and its involvement in pore complex assembly processes. We have shown previously that p68, which is the major wheat germ agglutinin (WGA)-binding glycoprotein of nuclear pore complexes from Xenopus oocytes, is located in the pore channel and participates in mediated transport of karyophilic proteins. Using a monoclonal antibody directed against p68 (PI1) we removed this protein from Xenopus egg extract by immunoadsorption. On addition of lambda DNA the immuno-depleted extract supported reconstitution of nuclei which were surrounded by a continuous double-membrane envelope but lacked pore complexes and were unable to import karyophilic proteins such as nucleoplasmin or lamin LIII. Essentially identical results were obtained with extract depleted of WGA-binding proteins. Our finding that both the anti-p68 antibody and WGA efficiently removed components from the extract necessary for pore complex assembly but did not interfere with nuclear membrane formation demonstrates that these processes are independent of each other. Analysis of the immunoprecipitate on silver-stained SDS-polyacrylamide gels indicated that the antibody adsorbed other proteins besides p68, notably two high molecular weight components. By sucrose gradient centrifugation and gel filtration we showed that p68 together with associated protein(s) forms a stable, approximately globular complex with an Mr of 254,000, a Stokes radius of 5.2 nm and a sedimentation coefficient of 11.3 S. Our finding that p68 occurs in the form of larger macromolecular assemblies offers an explanation for the distinctly punctate immunofluorescence pattern observed in the cytoplasm of mitotic cells after staining with antibodies to p68. PMID- 2101353 TI - Retinitis pigmentosa associated with glaucoma--clinical analysis. AB - A clinical analysis of Retinitis Pigmentosa (RP) was made in 2,789 eyes of 1,400 patients seen over a 5 year period (1983-1987), 64 eyes of 32 cases (2.3%) of RP associated with glaucoma were investigated. Of these 32 cases, the angle closure glaucoma was much more than the open angle glaucoma (30/2). More than half of the 32 cases were without cupping of disk, 5 cases did not have the glaucomatous damage to disk in spite of persistent elevated intraocular pressure for 0.5-5 yrs under the maximum medical therapy. 31 cases (97%) had subnormal blood pressure compared with the normal blood pressure value in different age groups. Histopathologic changes of the trabecular meshwork (TM) of 14 eyes showed a little bit more pigment cells in the TM than normal subjects, no typical features that would obstruct the outflow channels. PMID- 2101354 TI - The embryonal development of the human eye photoreceptors. AB - The development of the photoreceptors of human embryos and fetuses dating from 7 weeks to term were studied. The outer segments of rods and cones began to form at the seventh month. The arrangement of the newly formed discs were not regular, but at term they were arranged parallel to each other and perpendicular to the long axes of the outer segments. At the 9th month, no phagosome containing discs was seen in the pigment epithelial cells, but they were discerned in those of the term fetuses. PMID- 2101355 TI - Clinical application of microcomputer to visual function examination. AB - Microcomputer technique is put into use in ophthalmological clinical visual function examination. In visual EOG, ENG, visual tracking, contrast sensitivity and VEP examination, objectifying and standardization of experiment and data analysis are achieved by computer technique. In addition, a lot of manpower and time is saved, test results are obtained faster and more accurately. The basic rational of computerization in clinical visual function examination is presented. PMID- 2101356 TI - Micro-vitreous surgery combined with scleral encircling for the management of complex retinal detachment. AB - 50 cases (50 eyes) of various complex retinal detachments (RD) were treated with a combination of vitrectomy, membrane peeling, intraocular air tamponade and scleral encircling. RD with opaque media, RD with proliferative vitroretinopathy, traction RD due to trauma or other factors, RD with posterior breaks, and giant tears were included. During the follow-up periods of 3-12 months, 27 cases (54%) obtained anatomic reattachment, 23 failed (46%). Of the successful case, 24 eyes achieved improvement, 2 eyes remained unchanged, and one eye became worse in their vision. The surgery complications were: retinal haemorrhage, choroidal haemorrhage, iatrogenic tears, and the development of cataract. PMID- 2101357 TI - ERG characteristics of congenital stationary night blindness. AB - The ERGs of 9 cases (18 eyes) of congenital stationary night blindness with normal fundi or myopia were tested. All eyes showed nonrecordable rod ERG and cone ERG with normal a-wave. Scotopic mixed ERGs were of the negative type in 7 eyes and of the subnormal type in 11 eyes. The b/a ratio was reduced in all eyes. The ERG characteristics are useful for the classification, estimation of the probable location of the lesion, and differential diagnosis of the disease. PMID- 2101358 TI - Visual disabilities related to intraocular lens design. AB - Intraocular lens implantation after cataract extraction has become a common practice in the United States. However, unwanted optical images can correct an otherwise successful surgery into one that causes patient dissatisfaction. Refinements in manufacturing design and finishing have greatly improved the quality of present day intraocular lenses, but there is continued interest in simulating the optics of the human crystalline lens. We will discuss the optical requirements of intraocular lenses and how these are influenced by optic design and dimension, and spectral transmission characteristics. PMID- 2101359 TI - The proportion of various types of congenital color vision defects. AB - One hundred and three color vision defective subjects were screened from 3456 middle school students with pseudoisochromatic plate test. One hundred subjects out of them were further examined with a test battery including Panel D-15 and FM 100-hue test and Neitz anomaloscope test. It was found that there were 21 protanopes (P), 3 extremely protanomalous (EPA), 13 protanomalous (PA), 25 deutenopes (D), 5 extremely deuteranomalous (EDA), 28 deuteranomalous (DA), 6 unclassified subjects in our investigation. The proportion of various types of congenital color vision defects was P:EPA:PA:D:EDA:DA = 1.00:0.14:0.62:1.19:0.24:1.33. PMID- 2101360 TI - Zhongshan Ophthalmic Center. PMID- 2101361 TI - Penetrating keratoplasty combined with cataract extraction. AB - The authors report the results of penetrating keratoplasty combined with cataract extraction in 50 cases. The rate of transparent grafts was 62% after an average follow-up of 19 months. 60% of the patients restored their vision to 0.1 and better. The rate of transparent grafts and visual improvement did not correlate with the mode of cataract extraction; however, the extracapsular procedure had less vitreous during operation than the intracapsular modality did. The authors recommend that the combined operation be adopted for patients with corneal opacity and cataract, and preferably using the extracapsular mode. PMID- 2101364 TI - [The analysis of foreign bodies in the anterior chamber in 165 cases]. AB - One hundred and sixty-six eyes of 165 patients with foreign bodies in the anterior chamber who were treated at our center from 1966 to 1988 were retrospectively reviewed. Among them there were 109 eyes with nonmetal foreign bodies, 55 eyes with metal foreign bodies and three eyes with foreign bodies of unknown nature. Most of these foreign bodies were stone or iron. 83.6% of the patients were in the age range from 7 to 40 years, and the left eyes were affected more than the right eyes. Mostly, the foreign bodies were located on the surface of iris (97 cases) and at the anterior chamber angle (40 cases). The rates of blindness were 27.8% and 16.3% before and after operation. The postoperative visual acuity were: 0.05-0.2 in 27 eyes, 0.3-0.9 in 66 eyes, greater than 1.0 in 43 eyes and the rest of the eyes lower than 0.05. The presurgery treatment such as miosis and reduction of intraocular pressure, the selection of operative methods according to the nature, size, location of the foreign bodies and tissue wrapped up were discussed. If combined procedures should be done, it is better to remove the foreign bodies first and then perform the operation for complications. PMID- 2101366 TI - [Visual pigment genes for color vision defects]. AB - Applying recombinant DNA techniques, the structures of red pigment gene (RPG) and green pigment gene (GPG) were analyzed for 43 patients with protan or deutan (including 3 females), 4 normal relatives and 3 carriers out of 3 families, as well as 11 normal controls. Abnormality of RPG was detected in all 19 protan and that of GPG was found in 14 out of 24 deutan. In about 80% (32/40) of protan and deutan the changing of exon 5 for RPG or GPG was discovered. In protan the normal RPG was replaced by a 5' red -3' green hybrid gene. Some of the deutan had no GPG, some had 5' green -3' red hybrid gene with or without GPG. Furthermore, the exon 5 of RPG and GPG was amplified by polymerase chain reaction (PCR) and further analyzed by Rsa I digestion. The results for PCR are identical to that of Southern blot hybridization. PMID- 2101368 TI - [The visual-vestibular interaction in normal subjects]. AB - Full-field optokinetic nystagmus (OKN) at constant speed of 40 0/s and 60 0/s, vestibular ocular reflex (VOR) (sinusoidal 0.2 Hz, 60 0/s peak velocity) with different background (light and dark) and VOR-fix were observed in 72 normal subjects (144 normal eyes). The gain, FCV and DP of OKN, VVOR, VOR were also analysed. The gain of OKN is reduced accompanied with stimulation increasing, while the FCV is increased. The gain of VVOR is 1.08 +/- 0.09 (X +/- SD), while the gain of VOR is 0.64 +/- 0.09. The FCV of VOR is much reduced than that of VVOR. The FCV in the groups under 30 years of age are much faster than the groups above 30 years of age. The VOR--fix gain is 0.05 +/- 0.04. The DP of OKN, VVOR, and VOR are 0.05 +/- 0.04. The results showed an co-operation between visual and vestibular systems and the results also suggested that the series methods of visual-vestibular interaction (OKN, VVOR, VOR, VOR-fix) might be useful in eye movement examination. PMID- 2101377 TI - [Pharmacodynamics of synthetic estrogens. A review]. AB - Some details about the function of natural and synthetical hormonas are reviewed, particularly estrogens as ethynyl estradiol and its 3, Methyl ether (mestranol); its peripheral concentration vs tissular hormonal contents, a relationship of biological importance as the first step in its hormonal action and the cumulative local effects that could explain some intra and extracellular phenomena. PMID- 2101378 TI - [Biophysical profile in prolonged pregnancy. Another alternative of fetal surveillance]. AB - The value of the biophysical profile scoring to predict occur-rate perinatal outcome in prolonged pregnancy, was assessed. 60 patients with the diagnosis of prolonged pregnancy were included in this prospective clinical trial. A fetal biophysical profile score, described by Manning and modified by Johnson, was recorded in all these patients. There were 40 cases (66%) with normal profile scoring 3 of which had a feature considered as perinatal morbidity (specificity 94.8%). In contrast, from 20 cases with abnormal profile scores, 18 (90%) had abnormal perinatal findings (sensitivity 85.7%). The false positive and negative rates were low, 10 and 7.5% respectively, and the global predictive value of this test was 90%. In our study the amniotic fluid volume was the profile variable most able to identify a compromised fetus and the second with the highest specificity. Although we had a high cesarean section rate, (71%), we suggest that with normal profile scores (greater than or equal to 8) and normal amniotic fluid volume, the fetal biophysical profile may be an accurate test in the evaluation of the fetal condition in this obstetric complication. PMID- 2101379 TI - [Colonic pseudo-obstruction (Ogilvie syndrome), associated with cesarean section. Report of 2 cases and review of the literature]. AB - We inform of two cases of pseudoobstruction of the colon (Ogilvie's Syndrome) secondary to cesarean section. The clinical picture, the diagnostic method and alternatives of treatment are analyzed. The importance of the knowledge of the syndrome and prompt diagnosis is emphasized. PMID- 2101380 TI - [Several new concepts on the terminal mechanism of mammal fertilization]. AB - We briefly reviewed some ionic mechanisms participating in the fulfillment of the acrosome reaction processes, indicating the results obtained by the simultaneous and dynamic quantitation of sodium, potassium, calcium and hydrogen concentrations in the in incubation medium of human spermatozoa induced to achieve the acrosome reaction through the addition of cAMP and follicular fluid. At the same time, the participation of zinc and some enzymatic activities, like phospholipase A2, in the occurrence of this process, is indicated. A study is done about the sperm nuclear decondensation mechanisms, pointing at the importance of various participants in this event, like the disulfide groups reducing agents, some metalic ions and the glycosaminoglycanes, as well as a proposal of a mechanism which could be physiologically functional for the in vivo occurrence of this phenomenon. Finally we present some results explaining the DNA synthesis activation, which is repressed in the spermatozoa since the spermiogenesis final stages, and is indispensable for the chromosomic duplication required during egg segmentation. PMID- 2101381 TI - Effect of protein rich diet during acute phase of dysentery. AB - Ninety six children upto the age of five years suffering from uncomplicated acute dysentery of less than 3 days' duration were studied to find out the impact of feeding of extra-protein rich diet during their acute phase of illness. These children were randomly allocated to either control group (receiving only hospital diet) and study group (receiving hospital diet and extra milk which constituted 30% of ideal total calorie requirement of patients. Patients in the two groups were comparable on admission. Forty percent reduced food intake was observed among the children of both the groups due to severe anorexia which was reflected by no significant differences in clinical outcome, anthropometrical measurements and haematological parameters between the two groups on day 7 of hospitalisation and on day 15 after discharge. PMID- 2101382 TI - Outbreak of dysentery due to nalidixic acid resistant S. dysenteriae 1 at Agartala, Tripura: a hospital based study. AB - During the epidemic of bacillary dysentery at Agartala, Tripura, a total of 62 hospitalized patients suffering from diarrhoeal diseases were studied during the later part (11-16 June, 1988) of the epidemic. Principal features of Shigellosis cases were discussed. Of these 62 cases investigated, 19(30.6%) cases had the mucoid diarrhoea. From them S.dysenteriae type 1 and S.flexneri had been recovered from 31.6% and 10.5% cases, respectively. All the strains of S.dysenteriae type 1 isolated during the period of investigation were resistant to nalidixic acid. PMID- 2101383 TI - Multidrug resistant epidemic shigellosis in a village in west Bengal, 1984. AB - An out break of acute bacillary dysentery in a village called Dhamasin in Hooghly district of West Bengal was investigated during March 1984. Forty seven percent of families were affected. A total of 91 cases and 2 deaths occurred amongst 937 people giving an over all attack rate of 9.7% and a case fatality rate of 2.2 percent. Highest attack rate (22.7%) was observed in below one year age group. Multiple drug resistant Shigella dysentery type 1 strains were isolated for the first time from 6 out of 22 cases sampled at the domiciliary level. The organism was never isolated earlier during last ten years of surveillance in the infectious Diseases Hospital, Calcutta. Identification of nature of this outbreak and it's causative agent helped to realise the potentiality of extensive spread and paved the way for further investigations. Public health authorities were buffled as the rapid spread of the disease throughout the entire state of West Bengal could not be contained in spite of instituting all probable control measures on war footing. PMID- 2101384 TI - Super ORS. PMID- 2101385 TI - Management of acute diarrhoea. PMID- 2101386 TI - ICDS scheme--current status, monitoring, research and evaluation system. PMID- 2101387 TI - Global review on ORT (oral rehydration therapy) programme with special reference to Indian scene. AB - This communication is an attempt to review the status and implementation of the Oral Rehydration Therapy in the programme for Control for Diarrhoeal Diseases. The Global and the Indian situations are separately discussed, with more emphasis on the latter. Use of Home Available Fluids (HAF), Salt Sugar Solution (SSS). Commercial packets of ORS and the Government supplied packets of ORS are also assessed. PMID- 2101388 TI - Etiological agents of diarrhoea. AB - Two decades of research have established newer pathogens and techniques in establishing several organisms of diarrhoeal diseases as aetiological agents. It is now possible to detect an agent in 80% of the situation of diarrhoea in a standard laboratory. The brief review describes the list of pathogens, their diagnostic techniques with short description on clinical and epidemiological status. PMID- 2101389 TI - A study on some diarrhoea related practices in urban Mirzapur. AB - In an operational research on the improvement of sanitation and water supply by an Indo-Dutch project at Mirzapur, UP, diarrhoeal morbidity was taken as an intermediate outcome variable for measuring the impact of the proposed intervention. In this study 350-410 under-five children were selected from 200 urban families of 3 slums and surveyed during 3 different seasons for 2 weekly recall of morbidity, treatment and feeding practices during diarrhoea. The prevalence of diarrhoea varied between 8.7% to 33%. Breast feeding was not restricted while other forms of feeding was continued in 57.1% to 66.3% of cases. Use of ORT increased significantly from 0% to 39.62% possibly as a result of health education. Reorientation of private practitioners to avoid use of unnecessary drug is suggested. PMID- 2101390 TI - Report of an outbreak of diarrhoeal disease caused by cholera followed by rotavirus in Manipur. AB - An outbreak of acute diarrhoeal disease between August and October 1985 in 3 districts of Manipur state was investigated amongst 9,29,077 population at risk. The overall attack rate and case fatality rate were 0.2% and 0.9% respectively. Hospital records revealed that 58.8% of cases occurred amongst older children above 5 years of age. V.cholera was isolated from 25.3% of cases sampled. Interestingly, increased frequency in weekly admission of cases amongst children during first two years of life increased in the beginning of October when the original peak of diarrhoeal outbreak was about to decline. The October peak was caused by rotavirus which could be detected from 50.0% of diarrhoeal children in this age group. This possibly reflected beginning of the usual rotavirus diarrhoea season in the locality. PMID- 2101391 TI - A profile of diarrhoea in an urban slum area. PMID- 2101392 TI - Effectiveness of oral rehydration salt solution (ORS) in reduction of death during cholera epidemic. AB - An extensive outbreak of acute gastroenteritis involving all age group of patients occurred during July-September, 1978 in the Central district of Manipur state. A total of 4469 cases occurred during the period. 45.7% of diarrhoea cases sampled and 47.6% of water samples collected from rivers were found to be positive for V.cholerae biotype EITor. Case fatality rate in this epidemic was exceptionally low (0.8%) which was attributed to the early domiciliary use of oral rehydration salt solution (ORS) in the affected villages. Utility of ORS in drastic reduction of case fatality rate during any epidemic situation was first of its kind in the Indian scene. PMID- 2101393 TI - Overview: sharpening the focus on ethnicity. PMID- 2101394 TI - Ethnicity and alcohol/drug use revisited: a framework for future research. AB - Despite the large pool of research findings pertaining to ethnic and racial variations in the use of drugs (including alcohol), the relationship between ethnicity and drug use has not been thoroughly examined. This paper describes some of the major findings regarding ethnic and racial variations in drug use, and examines the methodological limitations of such studies. Moreover, this paper addresses the problem of shortage of theoretical explanations for ethnic variations in drug use. It is argued that the variable of ethnicity has not been properly conceptualized and measured in most studies. Cultural and structural aspects of ethnicity at both the individual and collective levels are examined, and their possible contributions to more rigorous research on the relationship between ethnicity and drug use are discussed. PMID- 2101395 TI - Uses and misuses of the concept of ethnicity in alcohol studies: an essay in deconstruction. AB - The importance of ethnicity in relation to patterns of alcohol use and its outcomes is widely recognized but imprecisely reported. A deconstructionist approach analyzes five dominant models of ethnicity: as bureaucratic category, race, national heritage, religion, and special population. Each usage is found to be imprecise and unreliable, and many of the usages are garbled, with inappropriate comparisons commonly made among them. Despite methodological weaknesses in scientific terms, many such studies have been insightful and have offered useful support for the importance of sociocultural factors. Further specification of the nature of ethnicity, emphasizing social learning about alcohol, with increasing attention to intraethnic variation, holds promise for increasing our understanding. PMID- 2101396 TI - Perception of alcohol use and misuse in three ethnic communities: implications for prevention programming. AB - This article compares data about perceptions of alcohol use and misuse, including perceived patterns of use, extent of the problem, reasons for use, and causes and effects of alcohol misuse in the Chinese, Indo-Pakistani, and Latin American communities in British Columbia. The methodology employed is an adaptation of Neuber's Community Needs Assessment model, using data from three sources: (1) relevant literature, (2) interviews with designated key informants, and (3) interviews with selected potential program consumers within the community. This article focuses on data gathered from potential program consumers. Results indicate that alcohol-related problems are considered least serious and widespread in the Chinese community and considerably more serious in the Latin American and Indo-Pakistani communities. Family difficulties present themselves in all communities as both possible causes and major consequences of alcohol misuse. Finally, implications for developing culturally responsive prevention programs are drawn. PMID- 2101397 TI - Orthogonal cultural identification theory: the cultural identification of minority adolescents. AB - A theory of cultural identification is presented indicating that identification with different cultures is orthogonal. Instead of cultures being placed at opposite ends of a continuum, cultural identification dimensions are independent of each other, and increasing identification with one culture does not require decreasing identification with another. Studies of Native-American and Mexican American youth show that: (1) identification with Anglo (White American) culture is related to having Anglo friends and to family acceptance of an Anglo marriage, (2) identification with either the minority or the majority culture is a source of personal and social strength, and (3) this greater strength, however, does not translate automatically into less drug use, because drug use is related to how much the culture that the person identifies with approves or disapproves of drugs. PMID- 2101398 TI - Psychosocial and cognitive correlates of alcohol use in younger adult immigrant and U.S.-born Hispanics. AB - Hispanic groups, taken together, constitute nearly 9% of the U.S. population. Research undertaken in the last decade has demonstrated that segments of the Hispanic male population are particularly heavy drinkers and are at high risk for alcohol-related problems. This article reviews several of the most important studies of alcohol use and its consequences among Hispanics, and reports new data from a study of alcohol use and its correlates among 452 young adult men and women in Los Angeles. The findings show important differences between immigrants and U.S.-born Hispanics as well as clear gender differences in terms of alcohol use patterns, expectations about the benefits of alcohol consumption, and depressive symptomatology associated with the use of alcohol. These differences have implications for the design of prevention and treatment services for Hispanics and these are discussed. PMID- 2101399 TI - Social adjustment and alcoholism among Chinese immigrants in New York City. AB - Based upon the patient files (N = 132) maintained by the Chinatown Alcoholism Services (CAS), interviews with CAS staff, and the clinical experience of the authors with Chinese alcoholics, this paper describes the social contexts of alcoholism among a group of working-class Chinese males in New York City. It focuses on the relationship between social adjustment and drinking behaviors, and analyzes the meaning of alcohol use and abuse within the ethnic community. The paper also examines the role of significant others in the alcoholics' drinking and help-seeking behaviors. Finally, treatment and research issues pertaining to alcoholism among the Chinese are discussed. PMID- 2101400 TI - Estimating the effect of native Indian population on county alcohol consumption: the example of Ontario. AB - Multiple regression analysis of cross-sectional 1985-1986 Ontario county data indicated that the presence of Native Indians on reserves is a significant factor in explaining differences in county alcohol consumption levels. Consumption in counties with reserves was higher than in those without reserves by roughly 1.48 liters of absolute alcohol per adult; consumption increased as the Native reserve population increased (p less than 0.05). When income, employment, household crowding, type of industrial activity, northern isolation, and tourism were included, we could account for over 60% of the variation in alcohol consumption between Ontario counties (p less than 0.01). Every extra $1,000 in income per tax return was associated with a 0.297-liter reduction in absolute alcohol consumption. Efforts to reduce alcohol consumption in the Native population would have their greatest impact when associated with improved economic conditions. PMID- 2101401 TI - Selected references on topics related to ethnicity and adaptation. PMID- 2101402 TI - Aromatase activity in fetal gonads of mammals. AB - This is a review of work demonstrating aromatase activity in both ovaries and testes of mammalian fetuses. Studies on the regulation of this enzyme activity by gonadotrophins and other factors have also been reviewed. Finally, the significance of aromatase activity in conjunction with the role of estrogen in ovarian and testicular development has been considered. PMID- 2101403 TI - Regulation of neonatal rat lung compliance by beta-adrenergic receptor stimulation: effects of prenatal exposure to terbutaline or dexamethasone. AB - beta-Adrenergic receptor stimulation is thought to participate in the perinatal switchover of the lung to air-breathing. In the current study, we have determined whether prenatal exposure of rats to terbutaline (10 mg/kg on gestational days 17,18 and 19) exerts promotional effects on lung function solely through its immediate actions at beta-receptors or whether terbutaline influences subsequent reactivity to adrenergic stimuli; we have contrasted the effects with those seen with a glucocorticoid (dexamethasone, 0.8 mg/kg on gestational days 17, 18 and 19). On postnatal day 3, basal lung compliance and lung rupture volumes were reduced after treatment with either terbutaline or dexamethasone, effects related primarily to drug-induced growth retardation; these effects were not present if data were corrected for relative tissue size. Despite a slightly reduced basal compliance, prenatal terbutaline exposure markedly enhanced postnatal reactivity to acute challenge with isoproterenol. In contrast, dexamethasone primarily enhanced basal compliance (corrected for weight deficits), with only minor effects on the isoproterenol response. These results suggest that, rather than producing classical receptor desensitization, gestational exposure to a beta agonist sensitizes lung compliance to postnatal beta-receptor stimulation. Promotional effects of terbutaline on neonatal lung function are thus distinct from functional changes achieved with glucocorticoids, such as dexamethasone. PMID- 2101404 TI - Osteocalcin is vitamin D-dependent during the perinatal period in the rat. AB - The vitamin D-dependence of renal calbindin D-28K and osteocalcin during the perinatal period was studied in fetuses (days 18 and 21) and neonates (days 2, 12, 17 and 22) of rats fed either a standard diet (0.85% Ca-0.7% P; "high Ca-P diet" rats) or a mildly Ca-P restricted diet (0.2% Ca-0.2% P; "low Ca-P diet" rats). Body weight and plasma calcium levels were identical in both groups. Plasma 1,25(OH)2D concentrations were markedly higher in the low Ca-P diet rats at all stages of fetal and neonatal life (in 22-day-old neonates: 536 +/- 58 pg/ml versus 126 +/- 12 pg/ml). 1,25(OH)2D concentrations increased between day 18 and 21 of fetal life, remained constant between day 21 of fetal and day 12 of neonatal life, and increased sharply between day 12 and 17 in both groups; after day 17, 1,25(OH)2D concentrations increased further in pups fed the low Ca-P diet. Renal calbindin D-28K reached peak concentrations on day 12 of neonatal life; calbindin D-28K levels were similar in the high and low Ca-P diet rats at all stages of perinatal development. Plasma osteocalcin levels increased steadily during the perinatal period; at most stages of perinatal life, and already from the fetal period was osteocalcin higher in the low Ca-P diet rats than in the high Ca-P diet rats (in 22-day-old pups: 1106 +/- 47 ng/ml versus 429 +/- 14 ng/ml). Femoral osteocalcin concentrations were also increased in fetal and early neonatal (days 2 and 12) low Ca-P diet rats, while the femoral calcium content and concentration of these rats were decreased in the late neonatal period (days 12, 17 and 22). These studies indicate that osteocalcin is vitamin D-dependent in the fetal and neonatal rat. PMID- 2101405 TI - Effects of chronic instrumentation on fetal growth. AB - Chronically-instrumented fetal sheep are a commonly used animal model for the study of fetal growth and metabolism. In the current study, we wanted to test the hypothesis that instrumentation alone would alter fetal growth patterns. Thirty two animals in three groups were used: (i) non-instrumented animals (n = 10); (ii) instrumented with catheters in the maternal and fetal femoral artery and vein and electromagnetic flow probes on the main uterine arteries (n = 10): (iii) animals instrumented as group 2, but with the addition of a doppler flow probe on the common umbilical artery and a common umbilical vein catheter (n = 12). Animals in group 2 and 3 were monitored until 137 to 140 days of gestation, at which time they were sacrificed for fetal morphometric measurements. Instrumentation significantly (P less than 0.05) decreased fetal body weight, length, and thymus weights. Liver-to-body ratios increased (P less than 0.05) in both surgically-instrumented groups. The addition of the umbilical artery doppler flow probe and an umbilical venous catheter did not lead to any further alterations in fetal growth. The current study demonstrates that surgical instrumentation alone can lead to significant alterations in fetal growth. PMID- 2101406 TI - Lymphocyte proliferation and subpopulations in dementia of the Alzheimer type. AB - Lymphocyte proliferation in dementia of the Alzheimer type (DAT) was evaluated by the level of mitogen response using phytohemagglutinin, pokeweed mitogen, concanavalin A and staphylococcal protein A. Lymphocyte subpopulations in the peripheral blood were also investigated using a monoclonal antibody with a fluorescence-activated cell sorter. The mitogen response in DAT was not significantly different from that in the normal controls. Lymphocyte subpopulations (Pan T, helper T, suppressor T, B cell, HLA-DR positive cell and helper/suppressor ratio) in DAT were not significantly different from those in the normal controls. These results suggest that the lymphocyte proliferative response to mitogens and the subpopulations in DAT may be natural in the normal aging process. PMID- 2101407 TI - Fibroblast growth-stimulating activity in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis. AB - Increased fibroblast growth-stimulating activity (FGA) was found in bronchoalveolar lavage fluid (BALF) from sarcoidosis patients. For evaluation of the significance of FGA in disease activity and the pathophysiology of sarcoidosis, the FGA levels were compared with data on cellular analysis of BALF, serum angiotensin-converting enzyme (S-ACE) activity and chest radiograms. The FGA level was significantly higher in sarcoidosis patients with parenchymal involvement (radiological stages II and III) than in those without parenchymal involvement (radiological stage I). The FGA was positively correlated with albumin and fibronectin concentrations in BALF. However, it was not significantly correlated with the ratio of CD-4 + to CD-8 + T-lymphocytes in BALF or the S-ACE level, which are known to be useful in evaluating the disease activity of sarcoidosis. These results indicate that the diagnostic value of FGA is different from that of the lymphocyte subpopulations in BALF and S-ACE, and is useful in estimating the extent of parenchymal involvement in sarcoidosis. PMID- 2101408 TI - Soluble interleukin-2 receptors in pulmonary tuberculosis. AB - Serum levels of soluble interleukin-2 receptor (IL-2R) were measured in patients with pulmonary tuberculosis, nontuberculous pulmonary diseases (bacterial pneumonia, lower respiratory tract infection, lung cancer), and in normal volunteers. Patients with tuberculosis had increased levels of soluble IL-2R compared to normal controls. Abnormally elevated levels were also shown in patients with nontuberculous pulmonary diseases, suggesting that elevations of soluble IL-2R are not specific for tuberculosis. In patients with tuberculosis, elevated levels of soluble IL-2R were steadily decreased to normal levels during successful treatment. Additionally, soluble IL-2R levels in tuberculosis were closely correlated with adenosine deaminase levels. Thus, it seems possible that measurements of soluble IL-2R may be beneficial in the diagnosis and the management of patients with tuberculosis. Furthermore, we demonstrated that elevated levels of soluble IL-2R in tuberculosis appear to be a consequence of cellular activation of mononuclear cells and not to be the result of cell death with subsequent IL-2R release. PMID- 2101409 TI - Identification and characterization of a new variant of apolipoprotein E (apo E Kochi). AB - A new variant of apolipoprotein E (apo E), named apo E-Kochi, was identified in the sera of a 29-year-old male with hyperlipoproteinemia as characterized by a broad-beta band. The characteristic double bands of apo E were seen in the isoelectric focusing gel of very low density lipoprotein from the proband and three members of his family. Of the double bands from the probands, the more cationic component was identical to ordinary apo E3 and the other anionic band was located at approximately a distance of one-half charge to the anode side. This anionic band is a new electrophoretical isoform of apo E (apo E-Kochi), and the molecular weight by sodium dodecyl sulfate electrophoresis and its antigenicity against anti apo E serum are the same as apo E3. Sequence analysis of lysyl endopeptidase fragments showed that apo E-Kochi differs from normal apo E3 at residue 145, where an arginine residue is substituted for histidine. PMID- 2101410 TI - Skin involvement in Hodgkin's disease: a case report. AB - Skin involvement of Hodgkin's disease, which typically occurs in the advanced stage, is rare and is associated with a poor prognosis. We report a case of Hodgkin's disease which recurred solely in the skin and followed a favorable clinical course. A 44-year-old Japanese man was diagnosed as having a mediastinal Hodgkin's disease in January 1983. After a complete remission, recurrent skin tumors appeared in the left supraclavicular and anterior chest regions in March 1988. No evidence of lymph nodes or visceral organ involvement was detected. The tumors regressed after chemotherapy. There is no evidence of the disease 7 months after discharge. PMID- 2101411 TI - The occurrence of leukemia in a patient with pulmonary asbestosis. AB - A 77-year-old man, who had been a subway construction worker, was admitted to our hospital for surgical treatment of left cheek carcinoma and an examination for pancytopenia on November 17, 1986. Bone marrow aspiration revealed that 10% of the nucleated cells were blasts with morphological atypism. Bone marrow biopsy showed hypocellular marrow and a diffuse increase of argyrophil fibers with the presence of asbestos fibers was observed by microscope. A chest X-ray showed the findings of old tuberculosis and pulmonary asbestosis, and asbestos fibers were demonstrated in the broncho-pulmonary lavage fluid. He was diagnosed to have pulmonary asbestosis complicated with hypoplastic low percentage leukemia. PMID- 2101412 TI - A case of rheumatoid arthritis which developed after recovery from adult respiratory distress syndrome. AB - A 53-year-old previously healthy woman suddenly developed adult respiratory distress syndrome (ARDS) of unknown etiology. High-dose corticosteroid pulse therapy and artificial ventilation were started immediately and she dramatically responded to the treatment. However, soon after recovery from ARDS, she developed typical rheumatoid arthritis (RA). Although no apparent relationship between RA and ARDS was clear, this case is quite suggestive in the consideration of the etiology of ARDS. PMID- 2101413 TI - Primary chondrosarcoma of the lung--a case report with immunohistochemical study. AB - A case of primary chondrosarcoma of the lung is presented. The tumor, located in the medial segment of the right lower lobe, was successfully resected surgically. Clinical survey did not reveal any primary lesion elsewhere. The tumor consisted of myxomatous, chondromatous, and fibrous lesions. Immunohistochemical study revealed that tumor cells were positive for S-100 protein and vimentin, and negative for other antisera which characterize epithelial tumors. With these clinical, histological, and immunohistochemical studies we diagnosed the tumor as a primary chondrosarcoma of the lung. PMID- 2101414 TI - Primary diffuse tracheobronchial amyloidosis treated by bronchoscopic Nd-YAG laser irradiation. AB - A case of primary diffuse tracheobronchial amyloidosis in a 45-year-old woman is reported. Because of tracheal stenosis immediately beneath the vocal cords, due to amyloid deposits, she was treated with Nd-YAG laser irradiation. Immediately after treatment, symptoms such as cough, wheezing, and shortness of breath on exertion improved. Bronchoscopic Nd-YAG laser irradiation proved useful for the removal of amyloid deposits from the trachea in this patient. PMID- 2101415 TI - Hepatic involvement in graft-versus-host disease associated with blood transfusion. AB - A 73-year-old man developed graft-versus-host disease (GVHD) after blood transfusion; he developed hepatitis, fever, rash, and pancytopenia. Although similar cases have been previously reported, the spectra of their liver injury was not clarified. The clinical and pathological findings of this case and a review of earlier reports suggest a possible predominance of hepatocellular injury in cases of GVHD after blood transfusion, which is in contrast to the prevalence of cholestatic liver disease in GVHD following bone marrow transplantation. PMID- 2101416 TI - Tracheopathia osteochondroplastica complicated with thyroid cancer: case report and review of the literature in Japan. AB - A rare case of tracheopathia osteochondroplastica complicated with malignancy is reported. Further examination of hemosputum following thyroid cancer operation revealed an abnormal finding of the trachea, suggesting the recurrence of thyroid cancer. However, the serum level of thyroglobulin was within the normal range. In contrast, the findings of bronchofiberscopy and the histological analysis confirmed the presence of tracheopathia osteochondroplastica. Therefore, measurement of serum thyroglobulin level and the bronchofiberscopy procedure were valuable for the differential diagnosis of metastasis of thyroid cancer in this case. Additionally, case reports of tracheopathia osteochondroplastica in Japan are summarized. PMID- 2101417 TI - A case of primary mucinous cystadenocarcinoma of the appendix with elevated serum carcinoembryonic antigen (CEA). AB - We report a 69-year-old female patient with mucinous cystadenocarcinoma of the appendix and elevated serum carcinoembryonic antigen (CEA). Serum CEA levels were 27.6-37.8 ng/ml. An oval shaped cystic mass at the ileocecal region was consistently seen by several radiologic procedures such as, barium enema, ultrasonography, computed tomography, and magnetic resonance imaging. The tumor was resected, and the histopathologic findings indicated mucinous cystadenocarcinoma of the appendix. CEA was demonstrated in the neoplastic columnar cells in immunohistochemical studies. The literature on the determination of serum CEA level in adenocarcinoma of the appendix is reviewed. PMID- 2101418 TI - Magnetic resonance imaging as an effective tool for successful localization of superior mediastinal parathyroid adenoma. AB - Noninvasive diagnostic procedures for the preoperative localization of parathyroid tumors were performed on a 59-year-old woman with hypercalcemia. In this case, sonography and computed tomographic scanning could not pinpoint the location of the tumor. Thallium-201 and technetium-99m subtraction scintigraphy was also inconclusive in the precise localization of the tumor, but it did define the location retrospectively. However, magnetic resonance imaging (MRI) clearly demonstrated the parathyroid tumor as a high signal on T2-weighted image in the left upper part of the superior mediastinum. The intrathymic parathyroid oxyphil adenoma was resected. Therefore, MRI was considered an effective tool for the localization of parathyroid adenoma, particularly mediastinal parathyroid adenoma. PMID- 2101419 TI - Anti-DNA idiotypes and anti-idiotypes in systemic lupus erythematosus. PMID- 2101420 TI - Diagnosis of digestive tract cancer using cDNA probe and monoclonal antibody. PMID- 2101421 TI - Molecular diagnosis of leukemias using activated oncogenes. PMID- 2101422 TI - Clinical diagnosis of the pathogenesis of coronary spastic angina. PMID- 2101423 TI - Pathophysiological findings, treatment and prognosis of angina pectoris. PMID- 2101424 TI - Early and long-term results of percutaneous transluminal coronary angioplasty for angina pectoris. PMID- 2101425 TI - Prognosis of silent myocardial ischemia and its strategy for treatment. PMID- 2101426 TI - Clinical relevance of oxidative stress with special reference to organ microcirculatory disturbances. PMID- 2101427 TI - Possible involvement of free radical formation in post-ischemic neuronal damage. PMID- 2101428 TI - Role of neutrophil-derived oxygen radicals in ischemic mucosal injury and the mechanism of formation in the rat stomach. PMID- 2101429 TI - Active oxygen toxicity in renal diseases. PMID- 2101430 TI - Free radicals in multiple organ failure. PMID- 2101431 TI - [An epidemiological study of thyroid pathology in a group of hospitalized patients]. AB - The epidemiological impact of thyroid disease was assessed in a group of in patients from an area with a potential iodine deficiency. The overall frequency of thyroid disease in the three years studied was approximately 4.91%, with a prevalence of elderly patients and a bias towards the female sex of 8.14:1. Nodular, single and multiple lesions were observed in 3.74% of hospitalised patients, whereas malignant forms were limited to 1.98% of the patients with nodular pathologies. When thyrotoxic syndromes were classified it was found that there was a predominance of multinodular toxic goitres over Basedow's disease. These findings are discussed and compared to previously published data. PMID- 2101432 TI - [Seronegative hashitoxicosis in patient with rheumatoid arthritis]. AB - Hashimoto's thyroiditis is known to occur in conjunction with other autoimmune disorders including rheumatoid arthritis. We describe herein a patient with long before-onset seronegative rheumatoid arthritis who developed Hashimoto's thyroiditis and hyperthyroidism without serologic evidence of thyroglobulin, microsomal and/or anti-TSH receptor antibodies. The occurrence of these autoimmune diseases in individual patients suggests an imbalance in immune function which effects more than one organ system. The predisposition to this spectrum of autoimmune diseases may be genetically determined, with specific HLA haplotypes associated with a variety of autoimmune diseases. The case of this patient provides the demonstration that intrathyroidal lymphocytes in autoimmune thyroid disorders and T-lymphocytes in the synovium are responsible for mediating the glandular destruction in Hashimoto disease and intraarticular lesions in rheumatoid arthritis, since the disorders can exist without evidence of a systemic immune response. PMID- 2101433 TI - [Hormonal evaluation in the diagnosis of obesity associated with "primary empty sella"]. AB - To determine whether obesity associated with "primary empty sella" (PES) had a characteristic hormonal pattern, we evaluated the hormonal profile in 24 simple obese and 19 obese-PES women. The latter group showed a significant delta-GH and LH impaired levels as well as plasma beta-EP significantly higher. Hence, the beta-EP measurement could be used to predict the hormonal response in these women. PMID- 2101434 TI - [Caloric intake and bone mineral content in obese and normal weight subjects]. AB - Bearing in mind the reports which clearly document the constant dissociation between daily calorie intake from diet, obesity and the positive effects of the mechanical load on bone trophism, the possible correlation between total daily calorie intake of some nutrients (Ca, P and vitamin D) on the one hand, and bone mineral density (BMD) on the other was evaluated in 61 obese women. The results appear to indicate that the higher BMD in obese compared to normal weight subjects may largely depend on the presence of notoriously high estrogen levels which allow a better efficacy and use of dietary calcium. PMID- 2101435 TI - [Cardioscintigraphic evaluation of obese subjects with or without arterial hypertension]. AB - A group of normotensive obese subjects (group A), a group of hypertensive obese subjects (group B) and a group of control subjects (group C) were submitted to radionuclide ventriculography using 99mTc to investigate cardiac function and haemodynamic situation in the presence of an increased preload (group A), preload and afterload (group B). Results show a significant reduction in ejection fraction and systolic blood pressure/end systolic volume in group A. Group B shows better cardiac function probably for the presence of cardiac concentric hypertrophy. Left ventricle work either in a minute and for each beat is greatest in patients of group B. Thus the simultaneous presence of obesity and hypertension can cause a worse prognosis in such patients for cardiac ischaemia and/or sudden death. PMID- 2101436 TI - [Waist to hip ratio and the distribution of adipose tissue]. AB - The aim of the study was to assess the relation between the waist to hips ratio (WHR) and the distribution of adipose tissue in visceral or subcutaneous site through the use of CAT. Results are expressed as the ratio of visceral to subcutaneous adipose tissue area (VSR). A total of 61 patients were randomly selected for inclusion in the study. Contrary to normal weight subjects, obese patients did not reveal significant correlations between the two ratios. Following multi-variant analysis in normal weight subjects, WHR appeared to be influenced by sex, BMI and VSR. In patients with prevalently visceral adiposity WHR was determined by sex and VSR, whereas in patients with prevalently subcutaneous adiposity it was influenced by BMI alone. In conclusion, the significant correlations between WHR and tomographic indices of adipose tissue distribution reported in the literature are not present in all types of patient, and in particular are not found in obese patients and normal weight subjects with prevalently subcutaneous adiposity. PMID- 2101437 TI - [Lipolytic and lipoprotein lipase activity of subcutaneous and visceral adipose tissue in Cushing's syndrome]. AB - Cushing's syndrome has been recently compared to visceral-type obesity, since it is characterised by the accumulation of adipose tissue at a deep abdominal site, to the detriment of the subcutaneous adipose panniculus, and is associated with insulin-resistance and hyperlipemia. The aim of the present study was to evaluate the influence of glucocorticoid hormones on lipolytic activity (index of FFA mobilisation) and on lipoproteinlipase (LPL) activity (an index of the accumulation of triglycerides) in subcutaneous and perirenal adipose tissue in order to clarify the mechanisms involved in this type of accumulation in Cushing's syndrome. Five patients (4 F and 1 M) were included in the study, mean age 27.8 +/- 3.7 years and BMI 21.3 +/- 1.2 kg/m2; patients were hospitalised in the 2nd Surgical Clinic at the University of Padua and underwent surgery for secondary corticosurrenal hyperplasia with ACTH secreting hypophysial adenoma. Lipolytic activity in subcutaneous adipose tissue in these patients was significantly lower (p less than 0.05) than in control subjects, in particular after noradrenalin stimulation (p less than 0.01). No significant difference was observed when lipolytic activity in subcutaneous adipose tissue was compared to that one in perirenal tissue. LPL activity in subcutaneous adipose tissue did not reveal statistically significant differences compared to control subjects, although values were lower. A further decrease in LPL activity, which was not however significant, was observed in perirenal tissue in comparison to subcutaneous tissues in the same patients. The mean weight of adipocytes (ug) was slightly lower in subcutaneous adipose tissue compared to control subjects and even lower in perineal tissue in comparison to the subcutis in the same patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101438 TI - [Residual hyperinsulinism after glucose oral load in obese subjects with normal glucose tolerance]. AB - Forty-five NGT obese subjects were submitted to OGTT with IRI and CPR determinations and to euglycemic hyperinsulinemic clamp, and divided into two groups: A) those with return of insulinemia toward basal values, and B) those with residual hyperinsulinism, in order to evaluate possible differences in insulin secretion and/or insulin action among them. Our data show the younger age of those with residual hyperinsulinism, that also seems related to insulin secretion, represented by IRI and CPR basal values, but not to insulin resistance parameters. PMID- 2101439 TI - [Comparison of three methods for the rapid determination of body composition]. AB - The study of body composition is becoming increasingly important in the field of nutritional medicine. The possibility of assessing body composition easily and economically has therefore raised considerable interest. Using straightforward correlations, we have compared the data obtained from the assessment of BF% using plicometry, impedance analysis and the interactivity of close-infrared rays; in addition, we studied the possible influence of the distribution of fatty tissue, expressed as W/H, on the results obtained using these methods. One hundred and forty-eight subjects (51 M and 97 F) were studied aged between 13 and 76 years old, with BMI ranging between 16.8 and 56.4; subjects were divided into three groups according to BMI and W/H. The three methods proved to be well correlated in patients with BMI less than 30 (r between 0.92 and 0.74), whereas correlations were less marked and less significant in groups with BMI greater than 30. W/H seemed capable of influencing results obtained using these methods and this was more evident in results obtained using impedance analysis (p less than 0.0001). The three methods studied were comparable in normal weight and slightly overweight patients, whereas contrasting findings were obtained in patients with moderate and severe obesity. Extreme caution must therefore be used in interpreting the data obtained in these subjects. PMID- 2101440 TI - [Fetal macrosomia in children of diabetic mothers: relationship with excess weight in early years of life]. AB - One hundred children (4.1 +/- 1.9 years) were examined: 31 of type I diabetic mothers, 25 of type II diabetic mothers and 44 of gestational diabetic mothers. The fetal body weight index at delivery was determined according to Babson. The weight/height index was determined according to Tunner's Centiles, when the children were examined. At delivery 41% of babies examined was greater than 90 degrees C for gestational age; when the babies were reexamined 23% was greater than 90 degrees C. On the contrary, during the early years of life we found that the 51% of children is greater than 90 degrees C and of this, the 27% became obese. The diabetic mother's children develop obesity more frequently than those of non diabetic mother's ones. The body weight at birth influences but is not the cause of obesity in the early years of life. PMID- 2101441 TI - [Diet and psychological therapy in a group of severely obese patients]. AB - The authors evaluated the usefulness of the psychological therapy in addition to usual diet treatment. Fifty subjects with severe obesity, have been randomly assigned to two different treatment groups: a) diet; b) diet plus psychotherapy. At the end of the study only the patients treated with diet plus psychotherapy showed any highly significant body weight reduction and a better diet adherence. PMID- 2101442 TI - [Vertical gastroplasty. Evaluation of efficacy]. AB - The paper evaluates the results of vertical gastroplasty in the treatment of morbid obesity. A series of 34 patients (24 F and 10 M) with the following characteristics was included in the study: mean age 41 years, preoperative weight 141 kg, % of ideal weight 204%, BMI 49; mean follow-up was 35 months. Postoperative mortality was zero and there were reduced early and long-term complications. Mean weight loss, expressed as a percentage of overweight, at 6 months was 48.5%, 56.8% at 12 months, 63.4% at 24 months and 67.2% at 36 months. The authors conclude that, given the low incidence of complications and the satisfactory weight loss which was maintained long after the operation, vertical gastroplasty appears to be the preferred operation, since it represents a safe and effective method of treating pathological obesity. PMID- 2101443 TI - "Peer review and quality management: are they compatible?". PMID- 2101444 TI - The issue is not the usability of claims data but the quality of the indicators. PMID- 2101445 TI - Quality of care: measure with caution. PMID- 2101446 TI - Applying insurance claims data to assess quality of care: a compilation of potential indicators. AB - Insurance claims records, which document many aspects of the process and outcome of medical care, are a practical and unobtrusive source of data for monitoring the quality of care provided to enrollees--a purpose for which they are rarely used. Data for these potential indicators could be drawn from claims or other administrative data systems. The authors established categories of care that could be used to develop claims-based indicators and compiled an annotated list of broad indicators for assessing the quality of care. The compilation of indicators is preceded by a discussion of some of the issues and challenges facing those who use and interpret claims-based indicators of quality. PMID- 2101447 TI - Spinal pedicle finder for transpedicular screw fixation--design and early clinical result. AB - Spinal transpedicular fixation has gained widespread popularity in the past 5 years. In biomechanical studies, the deeply-inserted transpedicular screws withstood the largest number of cycles in the cephalad-caudad and medial-lateral direction before failure. However, in clinical practice, the risk of screw placement which is too far medially or too far laterally do exist. The optimization of increasing screw depth to avoid complication is of significant clinical importance. A Spinal Pedicle Finder (S.P.F) has been designed for transpedicular screws and a prototype has been completed. It is composed of an I shaped body with a pair of front rails and a pair of rear rails. The front rail comprises two positioning arms that fit against the laminal bony crest, and the rear rail comprises two guiding bases that provide the transpedicular pin inserted with a specific angle. Both positioning arms and both guiding bases can be adjusted synchronously, and the specific angle over the guiding bases can be pre-set preoperatively according to the angle of pedicle axis. To date, in 7 cases (5 fracture and 2 spondylolisthesis) transpedicular screw fixation has been applied by aid of the S.P.F. Two-level fixation was applied in a fracture group and three-level fixation was applied in a spondylolisthesis group. The position of the transpedicular screw has been checked by CT scan postoperatively. A total of 32 transpedicular screws were inserted and all were in the pedicle and vertebral body except in one instances. One transpedicular screw was malpositioned on one side, partially lateral to the pedicle. However, this malposition did not cause any neurologic problem, such as dural tear, nerve root injury or other. Clinical experience has demonstrated its efficacy and safety. PMID- 2101448 TI - Effects of long-term dietary restriction on body temperature are modified with increasing age. AB - Effects of long-term dietary restriction on body temperature and its circadian changes were investigated in 3.5- and 14.5-month-old male Long-Evans rats. Animals were either fed and libitum or kept on a restricted diet for 8 weeks. Purina Lab Chow was constantly available to the ad libitum-fed groups, while half portions of their daily food consumption were given to age-matched diet restricted groups every day. A highly significant lowering of body temperature in middle-aged diet-restricted (MR) rats was not observed until their food intake had been restricted for 5 weeks compared with that of the middle-aged ad libitum fed (MA) group as well as that of the young diet-restricted (YR) rats. Eight weeks after diet restriction, both the circadian pattern of body temperature and its diurnal peak-trough difference remained almost unchanged in all four groups, while the average body temperature of MR rats was greatly lower than that of the YR group and that of MA animals. No significant difference in average body temperature was found between the young ad libitum-fed (YA) rats and the MA group. These data suggest that the average body temperature and its circadian changes in ad libitum-fed rats, at least before the age of 14.5 months, is not age-related, while the effect of dietary restriction on body temperature may be modified with increasing age. PMID- 2101449 TI - The in vivo distribution of murine lymphokine activated killer cells in splenectomized host. AB - The in vivo distribution of intravenously injected lymphokine activated killer (LAK) cells, generated in vitro with rIL-2 from normal murine splenocytes, was studied in BALB/c mice and compared with that of normal splenocytes. Both normal splenocytes and LAK cells were labeled with 51Cr, and the results were analyzed at 6, 24, and 48 hours after injection by localization index as the parameter. After injection through tail veins of mice, LAK cells were found to migrate to the spleen, lungs, liver, lymph nodes, bones and the kidneys. The apparent increased distribution pattern of LAK cells to the lung at 6 and 24 hours after injection was not detected when normal splenocytes were injected. Since almost one third of the injected LAK cells were found to localize in the spleen, it was postulated that splenectomy would affect the in vivo organ distribution of LAK cells. Accordingly, the in vivo distribution of LAK cells in splenectomized mice was further investigated. Results indicated that splenectomy enhanced the convergence of LAK cells to the lungs, liver, lymph nodes and bones. Therefore, splenectomy may augment the therapeutic effect of the adoptive transfer of LAK cells in pulmonary, hepatic, lymph node and bony metastases. PMID- 2101450 TI - Force-time breakage characteristics of food during simulated initial phase of mastication. AB - With the long range goal of gaining an insight into force control and muscle recruitment, it seems necessary to understand the task given to the masticatory apparatus. The purpose of this study was to characterize food breakage properties, and to study the influence of different compression speeds and occlusal morphologies on the categorized food properties. Experiments were carried out by means of a standard Instron instrument, modified with a switching relay. A stylus with 45 degree angulation and an opposing copperplated lower arch of either human or Macaca fascicularis were used for approximation of the natural situation. Crosshead speeds of 2 and 5 cm/min were selected. For future application, monkey chow was chosen as the testfood. Six parameters were defined to categorize food properties, which were initial breakage force (IBF), initial force buildup (IFB), maximum breakage force (MBF), breakage point (BP), temporal location of MBF (TL), and total compression time (TCT). The results showed that the force-time breakage characteristics of monkey chow were affected by different compression speeds in some aspects. However, this was not the case for the alteration of occlusal morphology. PMID- 2101451 TI - [The reaction of the heart to radiation. II. Clinical studies]. AB - In a review the cardiac attendant reactions in tumor irradiation in thoracal area are represented by means of papers and experiences of our own. It is shown that the heart reacts differently on ionizing rays and in special cases it can become a critical organ for radiotherapy. The diagnostic practice and the phenomenon of pericardiac and myocardiac reactions are described in detail. Complications on coronary vessel system are not frequent but because of their clinical consequence always they have to take into consideration. Cardiac radioreactions can be transient or harmless but rarely can lead to vitally threatening situations. Therefore it is referred to symptoms, diagnostic proving and possible or necessary therapeutic measures. Because significant curative therapeutic results can be attained by radiotherapy in thoracal area and the chances for curing increase for many patients, a slight risk is justifiable for side-effects on healthy adjoining tissue. On the other hand undesirable side reactions can influence the life-quality of the tumor cured patients. Therefore a radiotherapy in intrathoracal tumors with the aim of healing without complications has to take into consideration the sensibility of heart in addition to those of lung and spinal marrow. Beside permanent development of physical-technical suppositions these biological aspects have a substantial influence on optimizing irradiation in thoracal area. Finally it is tried to formulate really existing possibilities reducing a risk for cardiac side-effects and to refer to prospective interesting problems. PMID- 2101452 TI - [Indications for radiotherapy of rectal cancer]. AB - Surgery and radiotherapy complete each other in local control of suffering from rectal carcinoma. A radiotherapeutic effect on tumor is secured often. The adjuvant radiotherapy is the most interesting indication, though the most controversial as present too. Analysing all data and with experiences of an own irradiation study we have not any doubt that the indication is qualified for a combined therapy, if the therapeutic aim with priority is to prevent a local relapse as the most frequent and complained of form of therapeutic failure. In this problem, radical irradiation forms, as pre- and accumulating irradiation (sandwich-technique) and after-irradiation, render superior to an exclusive pre irradiation. In result of this study we practise a preirradiation of 25 Gy with immediately following operation and an accumulating irradiation to 50 Gy in proved high-risk-stage (T greater than or equal to 3 NoMo,Tx N1-3 Mo). If there is a primary local incurability by tumor invasion into the neighbourhood a pre irradiation is done with 50 Gy and following explorative laparatomy within 4-6 weeks. Nearly 60% of these tumors become operable after that. Likewise we practise in unirradiated patients with locoregional tumor recurrence. Also here the extirpation quota of patients with general or systemic incurability, that a stoma construction is required in, we carry out a transanal tumor reduction and irradiate with 50 Gy after that. Especially this therapeutic principle has proved its worth in patients that are past eighty. Here with acceptable living quality and avoiding a stoma construction a survival can be reached that corresponds to the statistical survival of this stage of life. PMID- 2101453 TI - [A retrospective study of the results of postoperative radiotherapy of hypernephroma]. AB - Retrospectively the patients were analyzed, postoperatively irradiated because of a hypernephroidal kidney carcinoma during the years 1978 to 1988. With a total number of 44 patients 12 were in stage I (Robson), 13 in stage II, 17 in stage III and 2 in stage IV. The probabilities for a tumor-free survival of five years were 81%, 59% and 30% for the stages I to III. The local recurrence rate was 7%, caused by exclusion of clinically negative lymph-nodes from irradiation field. In addition to survival probabilities the complication rate of radiotherapy is analyzed too. To this additionally to analysis of symptoms of a possible side effect the nuclear medical investigation of function of the remaining kidney was done in 9 selected tumor-free patients being irradiated in different techniques. A normal function was found in all cases. No severe side-effects can be shown in irradiated patients. Consequently the postoperative radiotherapy in hypernephroma is a supportive therapy of advanced tumor stages without severe side-effects. Further and greater planned analyses are necessary to comprehend prognostic factors. PMID- 2101454 TI - [The results of radiotherapy of epicondylitis humeri using different dosages]. AB - In a prospective analysis the effectiveness of roentgen irradiation with minimal doses (daily single doses .03 Gy up to a total dose of 1.5 Gy) was investigated in 207 patients with an epicondylitis humeri. Compared with a group of 92 patients, who were irradiated with higher doses being in general use (weekly 2x single doses 1.0 Gy to a total dose of 4.0 Gy), the therapeutic results show no significant differences. After termination of the first irradiation series an improvement of complaints was seen in half of the patients (48.8% or 50.0%). A further increase of the quota in success to 74.9% or 70.6% was found 6 weeks after termination of irradiation. By reason of radiotherapeutic results, mainly attained in chronic states of epicondylitis humeri after primary conservative therapy without success for months and partly surgical pretreatment, the radiotherapy should be used more frequently than till now, especially in consideration of its slight side-effects and injuries of patients. PMID- 2101455 TI - [Changes in the concentration of N-acetylneuraminic acid in the blood of patients with bladder cancer during radiotherapy]. AB - The N-acetylneuraminic acid (N-ANA) concentration of serum in 24 patients with bladder carcinoma was measured with a modified Arzneibuch (D.L.) GDR-method before, during and after the postoperative radiotherapy. It was found that the N ANA-concentrations in the patients operated resulted in a dependence from tumor staging already before the radiotherapy. The N-ANA concentration rose with increased staging. A temporary enhancement of the N-ANA-concentration with the maximum between 20. and 25 radiation fractions occurred in patients of staging T3 and relapses as well as with tumor cells being only little differentiated. The results are discussed in relation to the clinical importance. PMID- 2101456 TI - Venoruton as a radioprotector: a haematological assessment. AB - Efficacy of Venoruton--O-(hydroxyethyl) Rutoside--as a radioprotector has been tested on haematological profile of rats which were subjected to whole body radiation (500 rads). The results show radiation induced lesions in respect of total (TLC) and differential leukocyte counts (DLC)/and haemoglobin are significantly lessened when Venoruton was administered prior to radiation exposure. PMID- 2101457 TI - [The hemostatic homeostasis of patients with malignant neoplasms of the larynx, stomach and uterine cervix during radiotherapy and radiosensitization with metronidazole]. AB - In 90 patients with malignant neoplasia of larynx, stomach and cervix uteri the functional state of hemostasis was investigated within the process of radiotherapy and in radiotherapy and radiosensitization by metronidazole. Aim of this work is to answer the question if metronidazole affects the state of organism besides its effect on radiosensitivity of tumor tissue, especially the system of hemostasis, the impairment of which can not seldom result in thrombohemorrhagic complications in oncologic patients as is known. It was pointed out that the thrombophilic status of the blood of patients with stomach carcinoma continues to be unchanged and the patients are endangered for thrombosis potentially. In consequences of radiotherapy and doses of metronidazole the capacity for adhesion is decreased in thrombocytes of patients with laryngeal and cervical carcinomas to a high degree, whereby the thrombogenic potential of blood is reduced and with that the risk for origin of intravascular thrombosis. PMID- 2101458 TI - [The radiation sensitizing activity of metronidazole and iso-metronidazole (1-(2 hydroxyethyl)-2-methyl-4-nitroimidazole)]. AB - The effect of irradiation, metronidazole and iso-metronidazole on survival and number of tumor cells was analysed in vitro in mice that were inoculated with La hemocytoblastosis--or Ehrlich-ascites-tumor cells after processing. It was shown that metronidazole and iso-metronidazole nearly have the same radiosensitizing activity on these conditions. The effect was dependent on concentration of compounds and cell type. With intraperitoneal application the iso-metronidazole was eliminated from Lewis-lung-carcinoma more slowly than from blood. PMID- 2101459 TI - Radiosensitization of the rats' rhabdomyosarcoma R 1 by chloronitroimidazole compound--P40 dependent on radiation dose in fractionated radiotherapy. AB - The radiosensitizing effectiveness of 1-(2-hydroxy-3-methoxy-propyl)-2-chloro-4 nitroimidazole (P40) dependent on various fractionated schedules was tested in the rat solid tumor, rhabdomyosarcoma R 1. P40 combined conventional fractionation of gamma rays exerted no radiosensitizing effect measured as local control and growth delay as well. In contrary, the significant sensitization has been noticed when nontoxic doses of the nitroimidazole were combined with higher (3.7 Gy) doses of radiation. Low toxicity of P40 is encouraging for further experimental studies. PMID- 2101460 TI - Development and distribution of cysts of an avirulent strain of Toxoplasma and the humoral immune response in mice. AB - An avirulent T. gondii strain isolated from a owl (Glaucidium brasilianum) produces randomly distributed cysts in the brain of mice which can survive to inocula as high as 1000 oocysts. Cysts appeared for the first time after 15 days of infection. Regarding to humoral immunity development due to our TCR-2 strain, detectable antibodies were found after 12 days of infection. PMID- 2101461 TI - Increase of sulfadiazine effect against Toxoplasma gondii by using watermelon or cantaloupe seeds. AB - In an experimental model the anti--Toxoplasma effect of watermelon and cantaloupe seeds, together with sulfadiazine (Sd7.5 and Sd15) given by oral route, were studied. Combination of any of these seeds with the drug was able to increase the survival time and cure some tachyzoite infected mice. The effect was produced either by peeled or complete seeds and more significant results were obtained when Sd7.5 and 10(3) tachyzoite inoculum was used in the model. Some Toxoplasma oocyst infected mice were cured with the seeds alone (75% for watermelon, 37,5 or 50% for cantaloupe. Body weight variations are independent of the treatment with Sd alone or in combination with watermelon or cantaloupe seeds. PMID- 2101462 TI - [An evolutionary hypothesis on the absence of the Diego antigen (Di-a) in Chibcha Amerindians]. AB - Diego blood group was studied in 141 Amerindian and Eskimo tribes from Alaska and Canada. Twenty six tribes (18%) did not show the Di-a antigen and 20 tribes (77%) were of the Chibcha linguistic Phyla. In the past, the Di-a absence has been related to several ecological factors such as climate and the presence of clines. I advance an alternative explanation regarding the loss of the Di-a allele in the Chibcha genetic divergence which occurred 6000-7000 years ago, as a consequence of random processes and not of natural selection. It is postulated that the Di-a allele is absent in this Amerindian groups only, and that the presence of the antigen in four tribes (Boruca, Ica, Kuna and Sumo) is due to gene flow across neighboring groups of different languages which carry the Di-a antigen. PMID- 2101463 TI - [The serum of newborn Clelia clelia (Serpentes: Colubridae) neutralizes the hemorrhagic action of Brothrops asper venom (Serpentes: Viperidae)]. AB - The ability of serum from nine newborn specimens of Clelia clelia (Colubridae) to neutralize hemorrhagic action of Bothrops asper venom was tested. All serum samples neutralized completely the hemorrhagic effect of the venom in mice. This finding shows that the neutralizing ability of C. clelia serum towards the hemorrhagic activity of B. asper venom is innate. PMID- 2101464 TI - Construction of an invertible DNA segment for improved antigen expression by a hybrid Salmonella vaccine strain. PMID- 2101465 TI - Recombinant bacterial ghosts as vaccines. PMID- 2101466 TI - Immunity induced by live attenuated Salmonella vaccines. AB - Studies on the degree and specificity of protection conferred by immunization with aroA salmonella live vaccines in BALB/c mice are described. Animals were immunized i.v. and challenged orally 3 months later to ensure that the vaccine had been cleared from the tissues. Vaccination with Salmonella typhimurium aroA SL3261 conferred very good protection against virulent S. typhimurium C5 (over 10,000 x LD50). The specificity of cross protection was studied using S. typhimurium, Salmonella enteritidis and Salmonella dublin for vaccination and challenge, including challenge with variants of S. typhimurium and S. enteritidis of similar virulence which differed in the main LPS (lipopolysaccharide) antigen (0-4 or 0-9). S. typhimurium SL3261 gave very good protection against S. typhimurium C5 (0-4), but no protection against S. enteritidis Se795 (0-9). However, challenge with strains differing in the main 0 antigens showed that, although protection was generally better to strains expressing the same LPS type as the vaccine, specificity of protection was determined more by the background (S. typhimurium or S. enteritidis) of the parent strain used for the challenge than by 0 factors 4 or 9, suggesting that other factors could be involved. The nature of the antigen(s) responsible for protection in this model is unclear, but it would not appear to be the main 0-specific antigen. An S. enteritidis Se795 aroA vaccine was far less effective than S. typhimurium SL3261; it conferred good protection against the homologous wild type at 2 weeks post-vaccination, but far less at three months (approx 10-200 x LD50). This was unexpected, as the persistence of the S. enteritidis vaccine in the liver and spleen was similar to that of S. typhimurium SL3261, and the S. enteritidis and S. typhimurium challenge strains were of similar virulence. An S. dublin aroA vaccine conferred similar protection against wild type S. dublin (approx 300 x LD50). PMID- 2101467 TI - Use of live attenuated bacteria to stimulate immunity. PMID- 2101468 TI - Cloning and characterization of a cytotoxin gene from Salmonella typhimurium. PMID- 2101469 TI - Diffuse adherence of enteropathogenic Escherichia coli strains. AB - For the identification and characterization of the factor(s) responsible for the diffuse adherence (DA) pattern of enteropathogenic Escherichia coli strains, E. coli strain 2787 isolated from a case of infantile diarrhoea was employed. A plasmid-derived 11-kb fragment was cloned into pBR322. The recombinant plasmid pIB6 was shown to confer the diffuse adherence phenotype on different E. coli K12 strains as well as pIB4, a plasmid with a 9.2-kb insert. The DNA fragment necessary for the expression of the DA phenotype could be reduced to 6.0 kb. Antiserum obtained against pIB4-encoded proteins recognized a surface-associated protein of about 100 kDa in Western blotting. The isolated 100-kDa protein was found to bind to HeLa cells. The antiserum against C600(pIB4) inhibits adherence of E. coli 2787 and C600(pIB6) to HeLa cells. For this reason, the protein is called adhesin involved in diffuse adherence (AIDA-I). PMID- 2101470 TI - Clinical and field trials with attenuated Salmonella typhi as live oral vaccines and as "carrier" vaccines. AB - In recent years there has been a resurgence of research to develop new and improved attenuated strains of Salmonella typhi to function as live oral vaccines against typhoid fever and to serve as "carrier" vaccines to express foreign antigens of other pathogens and deliver them to the immune system. Strain Ty21a has served as a prototype in clinical and field trials to identify the optimal formulations and dosage schedules for live vaccines and to quantitate the duration of protection that can be achieved. Clinical trials with three new attenuated S. typhi candidate vaccines, a Vi+ variant of Ty21a, an aroC,aroD double mutant recombinant strain and a cya,crp double mutant, are underway or will be initiated shortly. PMID- 2101471 TI - Salmonella vaccines with mutations in the phoP virulence regulon. PMID- 2101472 TI - Expression of hepatitis B virus antigens in attenuated Salmonellae for oral immunization. AB - The aim of our work is to identify hepatitis B virus antigens that can be stably expressed in attenuated Salmonellae and elicit protective immune responses as live oral route vaccines. As a first carrier system, we expressed T-cell and B cell epitopes of hepatitis B virus as fusion proteins with the non-toxic subunit B (LT-B) in attenuated Salmonellae. These recombinant Salmonellae elicited anti LT-B T- and B-cell immune responses and anti-HBV nucleocapsid antigen (HBcAg) T cell responses when fed to mice. To combine the protective potential and the high immunogenicity of HBc with the induction of virus neutralizing antibodies to HBV surface antigen, we constructed vectors expressing hybrid HBc/pre-S particles in which the pre-S epitopes were surface-exposed. With one of these vectors, stable constitutive high level expression of hybrid HBc/pre-S2 particles was achieved in several attenuated Salmonella strains. When recombinant Salmonellae expressing such hybrid HBc/pre-S2 fusion proteins were fed to mice, the animals developed high titres of anti-HBcAg-specific serum IgG after a single or multiple oral immunizations, depending on the strain used as a carrier. In addition, lower titered antibodies against the pre-S2 antibody-binding sites were elicited. This is the first HBV antigen eliciting high-titered immune responses after a single oral immunization in recombinant Salmonellae. The immunogenicity of periplasmic LT-B and cytoplasmic HBc/pre-S2 shows that surface exposure of a foreign antigen is not a prerequisite for its immunogenicity in live attenuated Salmonellae. PMID- 2101473 TI - Control of colonization by virulent Salmonella typhimurium by oral immunization of chickens with avirulent delta cya delta crp S. typhimurium. AB - Oral immunization with a delta cya delta crp Salmonella typhimurium strain has been shown to preclude colonization by wild-type, virulent S. typhimurium and induces humoral and cellular immune response in chickens. Intestinal tract colonization by the virulent challenge strain was used to determine the level of protection conferred by immunization with the delta cya delta crp mutant. The associated humoral and cellular immune responses were measured by ELISA and delayed-type hypersensitivity (DTH) tests, respectively. The levels of colonization by both Salmonella strains were determined by enumeration of viable cells in the intestinal tract. A reduction in faecal excretion of the wild-type strain was observed with a single oral immunization with the delta cya delta crp mutant, but caecal colonization was not affected. However, double oral immunization with the delta cya delta crp mutant precludes caecal colonization by the virulent strain. IgM, IgA and IgG were detected against sonicated Salmonella whole-cell antigens. Outer membrane and flagella proteins induced DTH responses, whereas lipopolysaccharide failed to do so. The effectiveness of the delta cya delta crp strain in reducing caecal colonization by the highly virulent challenge strain in chickens demonstrates that oral vaccination with the delta cya delta crp S. typhimurium should aid in eliminating Salmonella carriers in chickens. The elimination of these carriers on the poultry farm should help to control Salmonella contamination of poultry products, therapy improving public health. PMID- 2101474 TI - Vaccination of chickens with aroA and other mutants of Salmonella typhimurium and S. enteritidis. PMID- 2101475 TI - Expression of the envelope antigen of dengue virus in vaccine strains of Salmonella. AB - The envelope gene of dengue 4 virus (DEN) was cloned in a plasmid under the control of Escherichia coli expression signals. A clone that expressed 93% of the gene was found to be detrimental to the bacterial host. Another clone which carried only 76% of the E gene was found to be quite stable in vitro as well as in vivo. The killed recombinant bacteria induced antibodies in mice which recognized native DEN virus. Attenuated Salmonella typhimurium (SAL) strains carrying the DEN-E plasmid were tested for their efficacy as orally administered live vaccines. Protective immunization was assessed in a mouse model by immunizing three-week old BALB/c mice followed by challenge with DEN virus. It was found that these young mice were highly susceptible to the carrier SAL strains (M206 and aroA SL3261). Moreover, the SAL-infected mice were more susceptible to DEN virus challenge than control mice, suggesting that the SAL infection caused immunosuppression in these young mice. PMID- 2101476 TI - Protein antigens of Mycobacterium leprae. AB - Protein antigens of Mycobacterium leprae have been identified by screening the lambda gt11, pYA626 and pHC79::M. leprae genomic libraries with pooled sera from leprosy patients and with antiserum to M. leprae cell wall protein (CWP) aggregate. Immunological screening of the lambda gt11 library with pooled sera from 21 lepromatous (LL) leprosy patients resulted in the identification of 19 antigens that are apparently different from previously identified M. leprae antigens. Five additional antigens were identified by screening the lambda gt11 library with pooled sera from 30 borderline tuberculoid or tuberculoid patients. Four other antigens were identified by screening the lambda gt11 library with anti-CWP. Two groups of recombinant cosmids were identified by screening the pHC79 library with LL patients' sera: one group specified proteins that reacted with monoclonal antibodies (mAb) against the 65-kDa protein and against the 18 kDa protein; the other group specified a 15-kDa protein that did not react with any of the mAb that were tested. One pYA626 clone also specified a 15-kDa protein that reacted with LL patients' sera, but did not react with any mAb. Genes specifying several of these antigens have been subcloned into the Asd+ plasmid vector pYA292 and have been introduced into a delta cya delta crp delta asd Salmonella typhimurium strain to evaluate the ability of individual M. leprae proteins to elicit immune responses against M. leprae infection. PMID- 2101477 TI - OmpA-Haemagglutinin fusion proteins for oral immunization with live attenuated Salmonella. PMID- 2101478 TI - Immunization of mice with an attenuated Salmonella typhimurium strain expressing a membrane protein of Francisella tularensis. A model for identification of bacterial determinants relevant to the host defence against tularemia. AB - A 17-kilodalton (kDA) protein of the facultative intracellular bacterium Francisella tularensis is one of several membrane proteins that induce an in vitro response in T cells from F. tularensis-primed humans. A DNA fragment containing two genes, one of which encodes the 17-kDa protein, was cloned into an attenuated Salmonella typhimurium strain. Mice orally immunized with the recombinant S. typhimurium strain showed lower viable counts in livers and spleens after challenge with F. tularensis LVS (live vaccine strain) than did animals immunized with the non-recombinant strain. Cyclosporin A neutralized the protective effect of the recombinant S. typhimurium strain. PMID- 2101479 TI - New attenuated derivatives of Vibrio cholerae. PMID- 2101480 TI - Recombinant attenuated Vibrio cholerae strains used as live oral vaccines. AB - Although great strides have been made in the development of recombinant attenuated Vibrio cholerae vaccine strains, the task has not been as simple as once imagined. The initial vaccine candidates proved to be unexpectedly reactogenic but further derivatives, such as CVD103-HgR, are well-tolerated, immunogenic and protective after a single dose. In addition, this strain carries a selectable marker to distinguish it from wild strains and has been evaluated in a practical, lyophilized formulation (Levine et al., 1988b). While CVD103-HgR is being further evaluated in expanded trials, we are also investigating a new secretogenic factor which could possibly explain the diarrhoea seen with the earlier vaccine strains. Hopefully, these studies will achieve the long-sought goal of a safe and effective vaccine for the prevention of cholera. PMID- 2101481 TI - Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1. AB - Shigellosis is an invasive disease of the human colon which is particularly prevalent among children of the developing world. No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elicit protective immunity at the level of the colonic mucosa, which is the exclusive site of multiplication of causative microorganisms such as Shigella flexneri and Shigella dysenteriae 1. We have constructed such vaccine candidates based on the destruction of virulence genes responsible for selected steps of the infection process. In S. flexneri, a combination of two mutations impairing cell-to-cell spread (icsA) and aerobactin production and transport (iuc, iut) which support growth within tissues provide a well tolerated and protective vaccine prototype against shigellosis in macaque monkeys. In S. dysenteriae 1, similar mutations are currently being introduced, in addition to one which eliminates the catalytic activity of Shiga toxin. These mutants and others will be tested soon in human phase I trials. PMID- 2101482 TI - Hybrid vaccines using Escherichia coli as an antigen carrier. PMID- 2101483 TI - Delivery of the cholera toxin B subunit by using a recombinant Yersinia enterocolitica strain as a live oral carrier. AB - The gene ctxB encoding the cholera toxin B subunit was subcloned to design its production by Yersinia enterocolitica. It was joined in two ways to yopH, a gene of the virulence plasmid pYV specific to this genus. This gene encodes one of the major Yop proteins (YopH) secreted by bacteria incubated at 37 degrees C in a Ca(2+)-deprived medium. In a first construction, an operon fusion was obtained between ctxB and yopH so that CT-B and a truncated YopH protein were produced. The recombinant CT-B from Y. enterocolitica was structurally and antigenically similar to CT-B produced by Vibrio cholerae. In another construction, the fusion gene obtained directed the production of YopH'/CT-B hybrid proteins that were secreted by Y. enterocolitica. In both cases, Y. enterocolitica directed the production of the recombinant proteins only when the bacteria were incubated in conditions of Yops production. When bacteria carrying the operon fusion were given orally to mice, a clear serum antibody response against CT-B was detected by ELISA. According to immunoblot analysis, this response was only directed against the polymeric form of the B subunit. PMID- 2101484 TI - Recombinant BCG as a candidate oral vaccine vector. AB - Bacille Calmette-Guerin (BCG), currently the most widely used vaccine in the world, was originally administered for many years as an oral vaccine. The low frequency of serious complications, inexpensive production, and adjuvanticity make BCG an ideal candidate for a recombinant vaccine vehicle. Although mycobacteria are slow growing and not yet well characterized genetically, we have recently developed technology for the genetic manipulation of BCG and other mycobacteria. Phage and plasmid systems based on a shuttle strategy to manipulate DNA in Escherichia coli and transfer it to mycobacteria have been developed. We have established that the aminoglycoside phosphotransferase gene can be used as an effective selectable marker in the mycobacteria and that a foreign antigen from Mycobacterium leprae can be expressed in BCG. Furthermore, a thorough analysis of mycobacterial expression sequences has been undertaken to optimize the expression of foreign antigens in BCG. We constructed an expression probe shuttle plasmid with beta-galactosidase as reporter gene, and have used it successfully to identify multiple mycobacteriophage DNA sequences with varying levels of constitutive or regulable promoter activity. Further genetic advances required for development of recombinant BCG into an effective recombinant vaccine vehicle, including possibilities for oral administration, are adumbrated. PMID- 2101485 TI - Aromatic-dependent mutants of Aeromonas salmonicida. PMID- 2101486 TI - Experimental ovine salmonellosis (Salmonella abortusovis): pathogenesis and vaccination. AB - Salmonella enterica subsp. enterica ser. Abortusovis, a sheep-adapted serotype, causes a contagious disease. Abortion is the major symptom and the main source of contamination. Research on this ovine disease may aid farmers, but may also contribute to comparative biological knowledge. Innate resistance partly controlled by the Ity locus, increased resistance to reinfection and humoral and T-cell-mediated immunity were observations gained with a murine model. In ewes, abortion regularly occurs following subcutaneous challenge carried out from the third month of gestation onwards. This ovine model was used to evaluate prevention methods for Salmonella Abortusovis infection. One subcutaneous injection of a live attenuated lyophilized vaccine containing a selected streptomycin-independent reverse mutant was shown to protect ewes against abortion and excretion of Salmonella Abortusovis. This vaccine could be administered simultaneously with other commercial live vaccines such as Brucella melitensis Rev. 1 vaccine. In sheep, application of the vaccine to the conjunctiva (an easy, individual and hygienic route of mucosal vaccination) was followed by lymph node bacterial colonization and a serological response without local or general clinical reactions. The early events of natural infection remain to be explored, as do the mechanisms underlying the host specificity of Salmonella Abortusovis. PMID- 2101487 TI - Oral administration of TNP-Lactobacillus conjugates in mice: a model for evaluation of mucosal and systemic immune responses and memory formation elicited by transformed lactobacilli. AB - Safe live vector systems are being developed for oral delivery of antigens. A transformation system for indigenous Lactobacillus species of the gastrointestinal tract is described. Model systems were set up to evaluate immune responses. Orally administered trinitrophenylized (TNP) Lactobacillus were examined for their ability to induce immunological memory formation via determination of specific antibody titres in serum. We demonstrate a direct correlation between the level of systemic memory formation, as revealed by specific anti-TNP IgG serum antibodies, and the TNP substitution ratio of the Lactobacillus suspension used for oral priming. The specific IgG anti-TNP serum titres were comparable to or even higher than the titres of parental intraperitoneally primed animals. These results demonstrate the feasibility of using orally administered antigen-Lactobacillus as a future approach to vaccination. PMID- 2101488 TI - Recombinant cholera toxin B subunit and gene fusion proteins for oral vaccination. AB - The B subunit portion of cholera toxin (CTB) is a safe and effective oral immunizing agent in humans, affording protection against both cholera and diarrhoea caused by enterotoxigenic Escherichia coli producing heat-labile toxin (LT) (Clemens et al., 1986; 1988). CTB may also be used as a carrier of various "foreign" antigens suitable for oral administration. To facilitate large-scale production of CTB for vaccine development purposes, we have constructed recombinant overexpression systems for CTB proteins in which the CTB gene is under the control of strong foreign (non-cholera) promoters and in which it is also possible to fuse oligonucleotides to the CTB gene and thereby achieve overexpression of hybrid proteins (Sanchez and Holmgren, 1989; Sanchez et al., 1988). We here expand these findings by describing overexpression of CTB by a constitutive tacP promoter as well as by the T7 RNA-polymerase promoter, and also by describing gene fusions leading to overexpression of several hybrid proteins between heat-stable E. coli enterotoxin (STa)-related peptides to either the amino or carboxy ends of CTB. Each of the hybrid proteins, when tested as immunogens in rabbits, stimulated significant anti-STa as well as anti-CTB antibody formation, although the anti-STa antibody levels attained (c.a. 1-15 micrograms/ml specific anti-STa immunoglobulin) were too low to give more than partial neutralization of STa intestinal challenge in baby mice. The hybrid proteins also had a near-native conformation, as apparent from their oligomeric nature and their strong reactivity with both a neutralizing antibody against the B subunit and a neutralizing monoclonal antibody (mAb) against STa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101490 TI - [Bronchoalveolar lavage in patients surgically treated with extracorporeal surgery]. AB - Nineteen selected patients were operated of coronary artery bypass surgery or aortic valvular replacement. In this cohort a bronchoalveolar lavage was performed before and after cardiopulmonary bypass. A rise in the polimorphonuclear neutrophils count was found in the post-bypass lavage group. The increase on secuestration of neutrophils by the lung could be a manifestation of lung injury due to the cardiopulmonary bypass. A review of this topic is presented. PMID- 2101489 TI - Vaccines against enterotoxigenic bacterial pathogens based on hybrid Salmonella that express heterologous antigens. AB - In this report, we examine two aspects in the development of a vaccine against enterotoxigenic bacterial pathogens based on hybrid Salmonella that express heterologous antigens. First, we describe the construction of a non-toxic fusion peptide for immunization against Escherichia coli that produce heat-labile (LT) and heat-stable (ST) enterotoxins. For that construction, the 5' terminus of the gene coding for ST was fused to the 3' terminus of the gene coding for the binding subunit of LT(LT-B). The ST gene was constructed synthetically with appropriate restriction sites to permit in-frame, downstream insertion. Maximum expression of ST antigenicity was obtained when a seven-amino-acid proline containing linker was included between the LT-B and ST moieties. The purified LT B/ST fusion peptide consisted of a single polypeptide chain with an apparent molecular weight of 18,000. The LT-B/ST fusion peptide was non-toxic and immunologic determinants of both LT and ST were recognized by antibodies directed against the native toxins. Animals immunized with either crude or purified preparations containing the hybrid molecule produced antibodies that were able to recognize native toxin in vitro. Significantly, these antibodies were able to neutralize the biological activity of native ST. The second aspect reported here examines a mechanism for stabilizing expression of heterologous antigens in attenuated Salmonella mutants by integration of the heterologous gene (LT-B) into the chromosome of the carrier. A comparative in vitro study of the levels of expression of LT-B between the cointegrate strain and an isogenic strain carrying the LT-B gene on a multicopy plasmid demonstrated that the initial levels of expression of both strains is similar, that the plasmid-carrying strain loses the ability to express the heterologous antigen very quickly and that the cointegrate continues to maintain and express the antigen without the requirement for a stabilizing antibiotic. PMID- 2101491 TI - [Ceruminous adenocarcinoma: report of a case]. AB - A case of an adenocarcinoma of ceruminous glands located on the external auditory meatus is presented. It must be noted the discrepancy between the well differenciated histologic appearance and the markedly aggressive clinical course. PMID- 2101492 TI - [Clinical study and hormonal evaluation of a 48, XXYY male. Comparison with previously published cases]. AB - A new case of the infrequent 48, XXYY syndrome is presented. The somatomedin C and HGH values were high, perhaps playing a role in the above of the mean height of Klinefeter patients, of which this cromosomic abnormality is a variant. PMID- 2101493 TI - [Contraceptives and ischemic cardiopathy]. AB - The incidence of myocardial infarction is higher in women that use oral contraceptives. The most important pathophysiologic mechanisms are: a) modification of coronary risk factors: the pill produces an elevation of both serum cholesterol and trygliceride levels, increase of blood pressure and decompensation of diabetes mellitus; b) blood coagulation disorders: oral contraceptives increase platelet aggregation and fibrinogen blood levels, therefore they have a considerable thrombogenic capacity. At this moment there are several update publications concerning this matter; however most of the mechanisms involved in the increase of coronary heart disease in this specific group still remain unclear. PMID- 2101494 TI - [Antiphospholipid syndrome and cardiovascular disease]. AB - Recurrent thrombosis, abortion and thrombocytopenia are the most frequent manifestation of antiphospholipid syndrome, which usually presents antibodies against some anionic phospholipids. A few years ago, this syndrome was considered as a manifestation of systemic lupus erythematosus; nowadays it is classified as an isolated systemic lupus erythematosus; nowadays it is classified as an isolated autoimmune disease. Hypotheses have been proposed to explain the origin of antiphospholipid antibodies, including infectious and autoimmune diseases with high titles of anticardiolipin antibodies. Genetic factors have also been involved. Laboratory tests of choice for the detection of anticardiolipin antibodies are RIA and ELISA tests; there are some structural differences among them depending on the underlying disease. Hypercoagulability and recurrent thrombosis are the main features of this entity; ischemic heart disease is in this context of outmost importance. Despite the lack of any clinically demonstrated association between antiphospholipid syndrome and ischemic heart disease, there are many "in vitro" studies that support this possibility. PMID- 2101495 TI - [Congenital malformations of the atlas: classification and clinical significance]. AB - A classification of congenital anomalies of atlas is proposed in order to make a systematic approach to its radiological diagnosis. Atlas is divided in four areas (posterior arch, union of posterior arch and articulation, articulation and anterior arch) for isolated malformations and two more for occipito-atloid and atlo-axoid anomalies. The common anomalies and its possible clinical relevance in each area are described. PMID- 2101496 TI - [Oxyphillic adenoma as a cause of primary hyperparathyroidism]. AB - We describe three cases of women who developed symptoms of primary hyperparathyroidism originated by a parathyroid functional tumor. Ostoporosis, arterial hypertension and nefrolitiasis were the most frequent antecedents. The PTH and calcium levels in bood and urine were elevated. The CT and ultrasound confirmed the diagnosis of parathyroid tumor, which was identified histopathology as oxifilic adenoma. All patients underwent surgical treatment. We consider these cases of clinical interest because this kind of adenoma hardly ever produces hyperparathyroidism. PMID- 2101497 TI - [Urothelial tumor markers: update]. AB - The story of the search for tumoral markers of urotelial neoplasias is reviewed. Its routine use is at present difficult due to its technical complexity. The use of new monoclonal antibodies is a promising aspect. PMID- 2101498 TI - [Complementary chemotherapy of breast cancer; experience at the University Clinic of Navarra]. AB - From 1982 to 1989, 68 patients were treated with the diagnosis of breast cancer. 57 were premenopausal and 11 postmenopausal. The most frequent stage was T2N1 (44.1%) followed by T1N1 (20.6%). The mean dosage of chemotherapy given were 91.2% for cyclophosphamide, 88% for methotrexate and 94% for 5-fluorouracil. The treatment was well tolerated and the most frequent toxicity encountered was leukopenia. The disease free survival were 89.4% at 96 month for premenopausal and 63.3% at 68 month for postmenopausal. We have not seen any differences in the disease free survival in relation to the size of the tumor or the status of the hormonal receptors of the tumor. The most important prognostic factor were the number of positive axilar nodes affected and the dosage of chemotherapy. PMID- 2101499 TI - [To live and to die with dignity]. PMID- 2101500 TI - [Gastrointestinal endoscopy]. PMID- 2101501 TI - [History of the Mexican Association of Gastrointestinal Endoscopy]. PMID- 2101502 TI - [Endoscopy in upper gastrointestinal tract hemorrhage]. AB - There are several changes in the role that endoscopy plays in upper gastrointestinal hemorrhage. We propose indications and make point about the factors than an endoscopist must have in mind referring to timing the endoscopy study. In the experience of our Hospital (Hospital Central Norte de Petroleos Mexicanos, Mexico City), during 20 years we found a diminution in the prevalence of duodenal ulceration and an increase in gastric ulceration, erosive gastritis an neoplasies as causes of upper gastrointestinal hemorrhage. PMID- 2101503 TI - [Esophageal rehabilitation]. AB - We present a review of the esophageal rehabilitation proceedings support, doing emphasis in dilation, the most important point of the treatment. Also we review some historic aspects, indications, contraindications, as well as the complication of the procedures. PMID- 2101504 TI - [Foreign bodies in the digestive tract]. AB - Our experience in 10 years in management of foreign bodies in the Gastrointestinal Tract is presented. We are at the Urgency Department, Hospital General de Mexico, S.S. We made 5580 endoscopy studies, 457 (8.1%) being performed in search of foreign bodies, in upper and lower G-I. Confirmation and endoscopic management was done in 218 patients (47.7%), being excluded in 239 (52.3%). We used both, flexible and rigid scopes, with a lower percentage of complications and high rate success in removing theme. PMID- 2101505 TI - [Foreign bodies in digestive tract of pediatric patients]. AB - We present our experience in the endoscopic management of 421 children with upper gastrointestinal foreign bodies. Only in the 1% of the cases (5 patients) we had complications who needs surgical intervention. We found a 1.5:1 ratio in male/female and the highest prevalence in the 2 to 5 years group. Most common foreign bodies were coins and small metallic objects (59%) followed by small plastic by objects (35%) and seeds, fish bones and meat in 6%, meat in 6%. PMID- 2101506 TI - [Elective endoscopic sclerotherapy in esophageal varices]. AB - We present our experience with elective sclerotherapy in ten years. 64 male and 57 females, median age 52.5 years, were treated. Post-necrosis cirrhosis was the primordial etiology in 44% followed by alcoholic in 40%. In regards to Child classification, 51% were "C"; 24% "B" and 25% "A". With variceal eradication we found no rebleeding, but in those without changes in variceal size, it was 82%. At six months, control of variceal hemorrhage was respectively to groups A, B, and C. 86%, 71% and 63%. The control at long follow-up were respectively 74%, 68% & 57%. Survival was directly related to the level of hepatic function instead of sclerosis. Complications were 2 to be 3% being the most severe: pleural effusion; mediastinitis and fiber. Mortality was 0.8% in one patient with esophageal perforation. PMID- 2101507 TI - [Variceal sclerotherapy in children]. AB - The experience in the Endoscopy Unit at: Hospital Infantil de Mexico "Federico Gomez" in sclerotherapy is presented. It was done in 45 children. Good results were obtained in 31 (69%). Our complications were: Ulceration (53%); stenosis (11%); meningism (4%), pneumonia (2%) and esophago pleural fistula (2%). No mortality was found for the procedure. PMID- 2101508 TI - [Esophageal prosthesis]. AB - Esophageal carcinoma has a very poor prognosis instead its histological type. Survival at 5 years is below 15%. With the prosthesis there is a change in the quality of life, but not in prognosis. We present our experience and make point in the correct techniques. PMID- 2101509 TI - [Percutaneous endoscopic gastrostomy: indications, techniques and complications]. AB - We present a revision of techniques, indications and complications of percutaneous endoscopic gastrostomy, with emphasis in technical aspects who allows to perform a safe and simple procedure. It can be done with modification of Pezzer canullas, and easily obtained items who can be collected by any trained endoscopist. PMID- 2101510 TI - [Selective cannulation of Vater's ampulla]. AB - A review was done on the general aspects of Endoscopy Retrograde Cholangiopancreatography (ERCP) as a method of diagnosis. A brief description is made on the historical and technical aspects. Emphasis is made on the diverse diseases that exist on the biliary tract, pancreas and the ampulla, in which ERCP is indicated. The results are mentioned and compared with those of other diagnostic procedures. The most common complications are discussed, as well as why they occur, and how they can be avoided. Specific circumstances are mentioned in which ERCP has limitations. PMID- 2101511 TI - [Endoscopic pancreatography]. AB - A review was done on the Endoscopic Pancreatography as a method of diagnosis. Emphasis was made on the historical and technical aspects, indications, contraindications, limitations and complications of the method. Also, we reported our experience about Endoscopic Pancreatography. PMID- 2101512 TI - [Endoscopic sphincterotomy: long-term results]. AB - The indications and results of 316 endoscopic sphincterotomies (ES) performed during 13 years are described. The most common indications were choledocolithisis 83% and stenosis 17% including: papillary stenosis, Oddi's disfunction, cancer of the ampulla and terminal choledochus, biliary pancreatitis and benign strictures. Stones were retrieved from in 95% of cases. We had complications in 7%, hemorrhage was the most frequent. Three cases were operated because of perforation and bleeding with no mortality. We placed 11 papillary stents, 8 naso biliary drainages and 2 balloon dilatations. Comments are made on ES and recent advances in therapeutic endoscopy, dissolution and fragmentation of stones. Therefore, ES is a non-aggressive method, that diminishes hospital expenses and solves most of the cases in high-risk surgical patients. ES will play a very important role in the treatment of gallbladder and bile duct stones. PMID- 2101513 TI - [Endoscopic decompression of the biliary tract]. AB - A technical review is done about different approaches in endoscopic management of biliary tract decompression, with emphasis in the state of the art points who allows this goal. Mention is done in nasobiliary drainage, endoprosthesis and pneumatic dilation. PMID- 2101514 TI - [Percutaneous cholangioscopy. An alternative in the treatment of retained stones]. AB - We report our experience in the use of percutaneous cholangioscopy for extraction of retained stones in the biliary tract, at the Oncology Hospital, Centro Medico Nacional, IMSS, between July 1984 and January 1990. Ninety seven patients were evaluated; the endoscopic manipulation was successful in 82 patients (84.5%). The main causes of failure were: narrow fistula, impacted stone, very small stones and false way. There were minor complications on 13 patients, but in two cases intestinal perforation indicated laparotomy. No death was reported. The main disadvantage of cholangioscopy was the waiting period, necessary to obtain a strong fistula. Nevertheless, the endoscopist can also relay on other techniques, such as sphincterectomy; the choice depends of each particular case. PMID- 2101515 TI - [Colonoscopy and polypectomy]. AB - A review of colonoscopy and polypectomy is done, since its origins. A brief description of techniques and medication is presented, as well as indications, limitations and contraindications. PMID- 2101516 TI - [Colonoscopy in hemorrhagic lesions of the colon]. AB - Patients with this pathology represents a difficult problem in differential diagnosis. Clinical findings and radiologic studies could help but endoscopy is now the most precise method in order to determine the site and nature of hemorrhage. We performed 504 colonoscopies in colon hemorrhage finding that our most frequent cause were polyps in both, children and adults in 199 cases (39%); diverticular disease was the second with 131 patients (26%) and third carcinoma with 52 (10%). Other causes were amebic colitis in 47 (8%); inflammatory bowel disease in 28 (6%) and infectious colitis in 13 (3%). Risks, complications and limitations of colonoscopy, as well as its great utility in diagnosis and treatment of colonic hemorrhagic lesions are commented. PMID- 2101517 TI - [Immunodiagnosis of human leptospirosis by ELISA-IgM, employing different antigenic preparations from prevalent serovars of Leptospira interrogans]. AB - A comparative study among different serovars of Leptospira interrogans was performed in order to prepare antigens to detect IgM antibodies by ELISA in early and late phase of human leptospirosis. Ten serovars were chosen among the most prevalent detected by microscopic seroagglutination (SAM) in Sao Paulo city. Using ELISA-IgM five of them showed better results (canicola, hebdomadis, icterohaemorrhagiae, cynopteri and brasiliensis). These ones were also studied in a pool. The non-treated antigens showed higher reactivity than the Triton X-100 (4%/50 degrees C/4h). ELISA-IgM using individually or pool of non-treated antigens proved to be reliable with high sensitivity and should be used for an earlier diagnosis of leptospirosis, as a trial test. Faster diagnostic elucidation can be useful to detect epidemic situations, so, allowing epidemiological surveillance interventions. PMID- 2101518 TI - [Renal changes caused by pentavalent antimonial (Glucantime) hypersensitivity in American tegumentary leishmaniasis. Report of a case]. AB - The authors report one case of leishmaniasis in a 60 year old patient who developed renal failure after treatment with Glucantime. With the interruption of these drug the patient recovered her normal renal function, and a new treatment with Amphotericin B was tried with complete cicatrization of the lesions. PMID- 2101519 TI - Thrombocytopenia and leptospirosis. AB - The present study has intended to contribute to the elucidation of the pathogenic mechanisms, involved in the thrombocytopenia and in the bleeding diathesis seen in the course of Leptospirosis. The group of cases included in the present prospective study consisted of 30 patients with Leptospirosis, admitted to the Infectious and Parasitic Diseases Ward, Hospital das Clinicas, Faculty of Medicine, University of Sao Paulo. The following possible mechanisms of thrombocytopenia have been considered and therefore investigated: platelet consumption, due to disseminated intravascular coagulation; immune-mediated platelet destruction, due to platelet-associated antibodies and an inhibited platelet production in the bone marrow. Thrombocytopenia occurred in 86.6% of 30 patients and did not seem to be immune-mediated by platelet-associated antibodies. Furthermore it did not seem to be due to a disseminated intravascular coagulation consumption. Although there was a statistically-significant correlation between bone marrow platelet production and platelet counts we think that the static microscopic examination of a bone marrow aspirate cannot accurately depict the dynamic mechanisms of platelet production when these cells are being consumed in peripheral blood. Vasculitis should be considered as the most important factor for the pathogenesis of the bleeding disturbances in Leptospirosis. However, we believe that thrombocytopenia, uremia and coagulation disorders, individually or as a group, should be included among the contributing factors that lead to and worsen bleeding episodes, which represent the leading cause of death in this disease. PMID- 2101520 TI - Screening the mutagenic activities of commonly used antiparasite drugs by the Simultest, a simplified Salmonella/microsome plate incorporation assay. AB - The mutagenic activities of 16 anti-parasite drugs were screened by the Simultest in both qualitative (spot test) and quantitative (plate incorporation) assays with a Salmonella typhimurium pool composed by the indicator strains TA97, TA98, TA100 and TA102. Four anti Chagas' disease drugs (nifurtimox, benznidazole, CL 64,855, and MK 436) and two anti-amebae drugs (metronidazole and tinidazole) gave positive results in qualitative tests and incorporation of rat liver microsomes did not alter the results. Comparative dose response curves of the mutagenic activities of CL 64,855, metronidazole and benznidazole obtained by the simultest and by individual Salmonella indicator strains demonstrated that both approaches have similar sensitivities. The results corroborate the validity of the Simultest, as a simplified, fast and economic version of the Ames test in preliminary screening of potential mutagenic drugs. PMID- 2101521 TI - [Detection of asymptomatic carriers of hydatid cysts: specificity increase of the immunoenzyme assay]. AB - An enzymoimmunoassay (EIE) as a screening test to select potential asymptomatic cyst carriers among the general population of areas under risk is being used in programs for the control of hydatic diseases caused by Echinococcus granulosus in Argentina. The experience obtained up to date, applying this assay in population surveys, indicates that depending on the prevalence in the area 10% to 30% of the individuals selected did not show images compatible with hydatic cysts. The purpose of the present study was to improve the specificity of the test. To this purpose, the influence of the modification of the antigenic availability and the effect of the absorption from the serum samples of antibodies anti-normal ovine sera and anti-phosphorylcholine was evaluated. One hundred and fourteen non hydatic sera selected because of their high cross reactivity in EIE using the whole hydatid antigen (WHA) and 118 hydatid sera, were studied with four fractions of ovine hydatid cyst fluid. The EIE employing the S2B antigenic fraction with previous absorption of the sera (EIE-S2B/A) was the system that discriminated better hydatid sera from non hydatid sera with high levels of cross reactivity. The replacement of the EIE employing WHA by the EIE-S2B/A system, for the active search of asymptomatic cyst carriers in field conditions, is proposed. The four antigenic fractions were analyzed by double diffusion and SDS-PAGE. The S2B fraction revealed a high content of parasitic components of less than 30 Kd which probably includes antigen B and subunits or fragments of antigen 5. PMID- 2101522 TI - Human parasitism by Phagicola sp (Trematoda, Heterophyidae) in Cananeia, Sao Paulo state, Brazil. AB - We report one case of parasitism by Phagicola sp. (Trematoda, Heterophyidae) in a 31 year-old woman who, in 1987, travelled and stayed several months in the municipality of Cananeia (SP), where she ingested, in various occasions, raw mullet (Mugil sp.). The patient referred mild intestinal pain and laboratory examinations showed eggs of Phagicola sp. in the stools and a slight increase in eosinophil blood levels (8%). After treatment with praziquantel (75 mg/kg per day for three days) all the symptoms and signs disappeared. This is, certainly, the first record of human infection by Phagicola sp. in Brazil and, perhaps, in countries other than the U.S.A. where unclear references to a few human cases were reported in the South-eastern region. PMID- 2101523 TI - Aerosolised pentamidine for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. AB - The goal of this study was to evaluate inhaled pentamidine for the treatment of patients with mild and moderate Pneumocystis carinii pneumonitis. Eight adults with AIDS and pneumocystis pneumonia (4 with a first episode and 4 with a repeat pneumocystosis) received daily inhalations of aerosol pentamidine isethionate for 21 days. Six patients were treated with doses of 300 mg of pentamidine and the remaining 2 received 600 mg every day. In the 300 mg treatment group, 2 individuals showed discrete and transient neutropenia. However, both subjects that received 600 mg of aerosol pentamidine daily developed leukopenia. One of them had major toxicity (overall severe intolerance of 12.5%) that required drug discontinuation and did not allow any analysis of the treatment efficacy. Of the 7 evaluable patients, 6 (88%) completed the treatment successfully. One subject of the 300 mg regimen experienced an early recurrence. In conclusion, inhaled pentamidine is an effective treatment for mild and moderate cases of P. carinii pneumonia. It is less toxic than standard anti-pneumocystis therapy and is suitable for outpatient use. PMID- 2101524 TI - Isolation of Leishmania sp. from aqueous humor of a patient with cutaneous disseminated leishmaniasis and bilateral iridocyclitis (preliminary report). AB - The authors report an uncommon case of leishmaniasis with disseminated cutaneous lesions, systemic manifestations and ocular involvement, the latter being characterized by bilateral nongranulomatous iridocyclitis. The severity of the ophthalmologic lesions and its unresponsiveness to therapy (in spite of satisfactory regression of both systemic and cutaneous manifestations) lead to a needle aspiration of the anterior eye chamber content. From this material Leishmania sp was isolated. To our knowledge this is the first time that Leishmania has been shown into the ocular globe. PMID- 2101525 TI - Pentavalent antimonial nephrotoxicity in the rat. AB - Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sbv (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis. PMID- 2101526 TI - Visceral leishmaniasis in AIDS patient. PMID- 2101527 TI - [The epidemiology of meningitis caused by Streptococcus pneumoniae in a metropolitan area, Brazil, 1960-1977]. AB - The epidemiology of meningitis caused by S. pneumoniae in the city of S. Paulo, Brazil, during the period 1960-77 is analysed. Data were obtained directly from the patients' records and registered on a pre-coded form. Cases of S. pneumoniae meningitis were confirmed by gram stain and/or culture of the cerebrospinal fluid (CSF). During the period 1960-77, there was confirmation of 1,965 cases of S. pneumoniae meningitis, giving an average rate of 1.9 per 100,000 inhabitants. Children of less than 5 years of age accounted for 52% of cases and 39% were less than 1 year old. The average rates for children below 1 year of age were 37 and 30 per 100,000 inhabitants, respectively, for the periods 1960-69 and 1970-77. The rate of incidence for the peripheral zone--2.2 per 100,000 inhabitants--was practically double the rate for the central area--1.2 per 100,000 inhabitants--in the 1960's. The age standardized rates were 1.6, 1.5 and 2.0 for central, intermediate, and peripheral zones, respectively. In the 1970's these rates were 1.4, 1.5 and 2.0. The average case fatality rate for the period was 47% which was inversely proportional to the number of CSF leucocytes at first examination. For children less than year old, the case fatality rate was 60% for the same period. PMID- 2101528 TI - [Visceral leishmaniasis epidemic in the State of Piaui, Brazil, 1980-1986]. AB - The kala-azar epidemic in the State of Piaui 1980-1986 is analyzed on the basis of the data collected by SUCAM Piaui. The outbreak began in towns of central and northern Piaui in 1980. In contrast what has happened in endemic periods in which the disease occurred in areas of higher altitude and semi-arid climate, the epidemic developed in humid tropical river valleys in rural zones. The epidemic was worst in the towns. The state capital, Teresina, hit in 1981, reached the epidemic peak in 1984 and accounted, for more than 60% of the 1,509 cases in the state. The epidemic was not substantial in those regions sprayed to combat malaria and Chagas' disease. While control in Teresina was attempted through intensive use of insecticides, the outbreak gave way spontaneously in rural areas. Neither the number of cases nor the phlebotomine population of Teresina presented significant seasonal variations but were moderately correlated. There was greater prevalence in children of 5 years of age or less, especially during the peak epidemic years, and much lesser prevalence in adults over 40 years of age. The geographical distribution of the epidemic process and its beginning, concomitant with a prolonged drought with its accompanying migration of people and domestic animals from endemic to epidemic regions, suggests that migration unleashed the epidemic. The fact that the epidemic process spontaneously relinquished its hold in areas where no control was attempted, indicates that the end of the epidemic cannot be attributed solely to measures of control. An analysis of the coefficients of specific incidence within age groups sparks the discussion about the possibility that progressive reduction of susceptibility (determined by the great number of asymptomatic infections as well as by long lasting immunity) contributed to the extinction of the epidemic. PMID- 2101529 TI - [The prevalence of anemia in pregnant women in their first visit to health centers of a metropolitan area, Brazil]. AB - Three hundred and sixty-three pregnant women enrolled in the Pregnancy Medical Care Program of S. Paulo Health Department from the district of Butantan, S. Paulo city, Brazil, were studied at the first routine consultation. At the time they were examined they were not given any medicine containing iron, folic acid or vitamin B12. Their average age was 25 and 65.9% belonged to families with a monthly per capita income below US$ 50.00. Only 3.1% had a per capita income above U$$ 150.00. The prevalence of anemia was 12.4%. The hemoglobin concentration (grams/dl) in the first trimester was significantly higher than in the second and third trimester of pregnancy. The prevalence of anemia in the first trimesters (3.6%) was significantly smaller than that found in the second (20.9%) and third semesters (32.1%). Those women who had had more than three gestations presented a higher prevalence of anemia than those with less than three, and the prevalence of anemia was higher in the group whose families had a monthly per capita income below US$ 25.00. PMID- 2101530 TI - [Reproductive variables and risk of benign breast diseases. A case-control study]. AB - The purpose of the study was the identification of risk factors for benign breast diseases (BBD); 257 women with BBD diagnosed through pathological anatomy or cytology and a matched control for each were studied. Subjects were selected at The State University of Campinas Hospital and at a private clinic. To enter the study cases had to have a first diagnosis of BBD between October 1979 and August 1984. The following BBD were considered: dysplasia, fibroadenoma, cystic disease, papilloma and ductal ectasia. Reproductive variables were studied as risk factors, including menstrual ovulatory cycles. The date on which the BBD was diagnosed was defined as the index date. For controls, data were considered up to when they had reached the same age as the matched case on the occasion of her diagnosis. Nulliparity was a risk factor for BBD. First birth at or above age 30 was a protective factor. Women who had used contraceptive pills for two or more years had a significantly lower risk than those who had never used them. The number of menstrual ovulatory cycles was not found to be associated with the risk of BBD. The results obtained from the study of Brazilian women confirm some of the conclusions found in the literature, mainly those that associate some reproductive variables with the risk of BBD. A few of these variables are also confirmed as risk factors for breast cancer. PMID- 2101531 TI - [Shelters of mosquitoes Culex (Culex) in rural zones (Diptera: Culicidae)]. AB - The human activities carried out in rural zones have been affecting the behavior of mosquitoes of the Culex (Culex) subgenera, which was the reason for undertaking this investigation with a view to registering data on the natural resting places in pastures and on the edge of or within primitive and residual forest areas. Three localities with different mesological conditions, as to type of human activity, all them situated in the Ribeira Valley region of S. Paulo State, Brazil, were chosen. The species most abundantly found were Cx. mollis (28.0%), Cx. declarator (25.0%), Cx. lygrus (13.0%) and Cx. coronator (9.6%). The collection of mosquitoes Cx. bidens + Cx. dolosus + Cx. chidesteri, known to be more urban, was much smaller than that of any other species of the group. With reference to outdoor environments, woodland contributed with 2,281 individuals (71.4%) suggesting their preference for this resting place, except for Cx. quinquefasciatus. Results are evaluated for the determination of the potential domicilation of each species and consequence of the same for the human population. PMID- 2101532 TI - [The control of solid waste with the participation of a low-income population]. AB - Two studies were undertaken with a view to improving the health conditions of a shanty town area in the city of S. Paulo, Brazil. The objective was to modify littering behavior and to implement litter-control procedures with the participation of the inhabitants. Results demonstrated the adequacy of the procedures adopted and suggest a possible contribution on the part of psychology to public health. PMID- 2101533 TI - [DMF index simplification in people aged 18 to 25 years]. AB - The DMF index can be estimated at double the value observed in the exam of two hemiarchs (Upper Right and Lower Left), or at four times the value obtained from six teeth (First Molar and Central Incisor Upper Right, first bicuspid upper left, second molar and lateral incisor lower left and second bicuspid lower right. The estimates were made by the use of methods of descriptive statistics, averages, percentages and the coefficient of the prevalence of caries, in a sample of 100 people, aged from 18 to 25 years. PMID- 2101534 TI - Supplementary feeding programs: a critical analysis. AB - A critical analysis of the Supplementary Feeding Programs which have been undertaken around the world is presented. Although only a few programs have been rigorously evaluated it seems that in relation to their main objectives, most of them have not proved to be successful. Some suggestions for improvement are put forward and the particular case of the Brazilian programs is assessed in detail. PMID- 2101536 TI - [The epidemiology of arterial hypertension]. PMID- 2101535 TI - [Smoking effects on pregnancy]. AB - A review of the literature on the effects of smoking on the health during pregnancy has been undertaken. Recent data on smoking patterns in the USA are listed and the gravity of the effects of passive smoking is brought out. The review of some new data shows that smoking in pregnancy increases the risk of fetal and infant mortality, and that the risk is dose-related. The factors by means of which smoking leads to the increase of fetal and infant mortality are given and include: low birthweight, premature rupture of membranes, abruptio placentae, placenta previa and tubal pregnancy. PMID- 2101537 TI - Changes in the spatial synchronization of the cortical electrical activity under extreme (hyperbaric) conditions. AB - Spectral correlation methods of EED-analysis were used to study the local synchronization (by power spectra--FFT) and the spatial synchronization (by assessing the coherence functions) of the cortical electrical activity of persons subjected to prolonged (one-month) extreme impact--hyperbaric conditions. Two neurophysiological mechanisms of system functional organization of the electrical activity of the central nervous system are described, through which the brain compensates its reduced functional capacities under the extreme conditions studied (including boundary physiological states). These mechanisms: (a) act in almost all situations of the extreme impact, irrespective of the scope of the remaining varied transient or lasting readjustments in the EEG, and (b) guarantee spatial interactions in the electrical activity in the brain in frequency ranges which are essential for its functions: alpha (8-12 Hz) and beta-2 (24-36 Hz). PMID- 2101538 TI - A study of ventricular electrogenesis and contractility in acute pressure overload of the right heart ventricle. AB - A model of fat embolism induced acute pressure overload of rabbit right ventricle of heart is presented. A decrease in right ventricular contractility is registered as early as the first minutes after loading. Changes in spatial magnitude and polar coordinates of vectors of ventricular depolarization, and myocardial ischemia manifestations are recorded. The changes in electrogenesis described are attributed basically to ensuing development of hemodynamic disorders. PMID- 2101539 TI - Hemisphere asymmetry in the detection of gratings of varying spatial frequency. AB - Visual field symmetry in contrast sensitivity was investigated under conditions of spatial uncertainty. The stimuli were sinusoidal gratings of varying spatial frequency (SF). They were presented randomly in the left, right or in both visual hemifields. The percent detected gratings were slightly higher than the gratings in the left visual field except for gratings of low SF (0.24-0.48 c/deg). The results suggest the existence of a slight left-field (right-hemisphere) superiority in detecting stimuli of medium and high SF. The asymmetry is too slight to allow any significant difference in the SF-content of the neural representation of the left and right halves of the images; neither might it provide an explanation of some recent data on hemispheric specialization, in particular visual tasks. PMID- 2101540 TI - Effects of nootropic agents on the performing of active two-way avoidance tasks in young and old rats. AB - Experiments were made on 2- and 18-month-old male rats to test the effects on the acquisition and retention of piracetam, meclofenoxate and four newly-synthesized substances with assumed nootropic action: pyrrolidine derivatives with code names p-F, p-P and A-T, as well as the derivative of para-chlorophenoxypropionic acid, with code name 4-Cl-alpha PA. The method of two-way active avoidance was used, with punishment reinforcement during 5-day training and retention tests on the 14th day after the beginning of training. The agents studied were applied orally in doses of 30 and 150 mg/kg for 3 days (2 days before training and on the first day of training) and then again one hour before the retention testing. The older rats manifested a poorer learning capacity than the younger ones. Piracetam produced the best effect both on learning and on retention. Compounds with code names p-F, p-P and A-T induced an increase in the number of avoidances compared with the controls on isolated days only, according to the tests for acquisition. The favourable effects observed are not in close dependence either on the dose applied, or on the age of the experimental animal. No significant effects were observed under the effect of meclofenoxate and of its structural analogue 4-Cl alpha PA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101541 TI - Optimal interelectrode distance with the method of source density analysis. AB - Three error sources which contribute to the total error of the second space derivative (SSD) used with the method of current source density analysis (CSD) were examined. The approximate formula usually used with CSD was the first error source. Another error originated from the finite interelectrode distance. The measurement error of the device with which the potential was recorded was the third error source herein considered. A relative SSD error was determined to estimate the effect of the errors examined. The experimental data (a section from the three-dimensional potential profile in annuran cerebellum produced by parallel fiber activation) were fitted by polynomials, Fourier expansion and cubic splines. Then a preferable interelectrode distance was obtained corresponding to the minimal relative error. PMID- 2101542 TI - Force platform for stabilographic studies. AB - An analysis is made in the paper of a triangular force platform included in a computer system for postural analysis using Pravets 8M personal computer. The tensions generated in steel rings in the three corners of the platform, proportional to the moments of the forces with spontaneous fluctuations of the position of the centre of the force exercised by the experimental subject on the platform, are registered and amplified using three identical amplifying channels comprising tensotransducer, preamplifier and second-order low-frequency filter. The output signals of the three amplifying channels are fed to an analogue decoder generating an electrical signal proportional to the weight and to the anterior-posterior and lateral components of the force. The signals from the outputs of the decoder can be used for introducing visual feedback about postural stabilization. The regulations of the platform are maximally simplified so as to be used in clinical research. PMID- 2101543 TI - Computerized system for posturographic research based on the ADAPT language for analysis of analogue signals. AB - A description is given of a system for posture analysis based on a specialized language ADAPT for analysis of analogue data, guaranteeing: 1. Analogue-to digital conversion of the input signals with dialogue determination of the conversion parameters and monitoring of the signals on the screen. 2. Storage of the data on a diskette in a format guaranteeing high density of the data and fast exchange with the computer. 3. Calculation of the following parameters of the stabilogram and statokinesigram separately for open and for closed eyes: a) Anterior-posterior and lateral components of the path of the projection of the force centre SPAP and SPLAT; b) Mean frequency of the sways: fAP and fLAT; c) Ratio between the anterior-posterior and the lateral sways: AP/LAT. d) Surface A covered by the shifting of the centre of force; e) The path (SP) of the centre of application of the force; f) Mean amplitude (MA) of the sways for one second; g) Mean frequency (MF) of the sways. Romberg's coefficients are calculated for all parameters. 4. High speed of the calculations. 5. Graphic and digital display of all results on the screen from where they can be transferred to a printer, if necessary. PMID- 2101544 TI - Evidence in support of a chemiosmotic mechanism for stimulated prolactin release. AB - In order to assess the involvement of a chemiosmotic mechanism in exocytotic prolactin (PRL) release, dispersed anterior pituitary cells from female rats were used. After primary culture they were incubated in media containing bicarbonate or isethionate ions, probenecid and carbonylcyanide p-trifluoromethoxyphenyl hydrazone (CCTP). Cells incubated without these additives or stimulated with dibutyryladenosine 3':5'-cyclic monophosphate served as controls. Further, a crude secretory granule suspension was used to study the effects of elevated osmotic pressures. The inhibition of anion transport with probenecid always significantly reduced PRL secretion, whereas bicarbonate ions had the opposite effect. The proton ionophore CCTP only inhibited stimulated release, and the substitution of chloride ions by isethionate was ineffective. Finally, it could be observed that elevated osmotic pressures reduced the lysis of isolated secretory granules when bicarbonate ions were present in the incubation medium. The results indicate that a mechanism requiring protons and bicarbonate ions is involved in stimulated PRL release and that a different mechanism, independent from proton gradients, should be considered for basal PRL secretion. PMID- 2101545 TI - [Peripuberal development of genetic obesity in beta rats. Daily changes in food intake, body weight, deep body temperature, triglyceridemia and glycemia]. AB - The moderate quality of beta obesity and its relatively slow evolution make it potentially useful for defining the sequence of events that lead to the overt syndrome. Estimates of food intake, live body weight, deep body temperature, triglyceridemia and glycemia were obtained at several times during the day in beta genetically obese and alpha (alpha) control male rats at peripuberal age, in order to characterize the dynamic phase of this obesity and to attempt the definition of some previous proceedings that eventually produce the full obesity syndrome. Beta higher food intake in the light cycle preceded its whole day hyperphagia. Both genotypes showed the normal pattern of predominantly nocturnal feeding. A lower light phase's weight loss in beta preceded the overweight. Thus, beta rats were not significantly heavier than alpha until the end of the last period studied, when they were 75 days old. A defect in adaptive thermogenesis in beta genotype is suggested, as values on deep body temperature in relation to alpha were significantly lower at all times of day tested. Correlation coefficient value between daily net weight gain versus deep body temperature was: r = -0.601 (p less than 0.01), suggesting a diminished lipolytic stimulation in beta brown adipose tissue. A sustained hypertriglyceridemia in beta at every time of the day studied suggested its endogenous source. Differences in glycemia values were not statistically significant between genotypes, though apparently wider variations in beta could reflect a certain glycemic regulation lability in the obese genotype. PMID- 2101546 TI - Influence of norepinephrine-sensitive intracellular calcium stores on the relaxant response to diltiazem in rat aorta. AB - The contractile response to norepinephrine (NE) in rat aorta has an initial fast (F) component attributable to Ca release, followed by a slow (S) component due to Ca influx. The relaxant action of the Ca entry blocker Diltiazem (DT) 10 microns was measured in three different responses to NE: a) a NE contraction in Ca = 1.35 mM (in which both the F and S components participate) was relaxed by 36 +/- 4%; b) previous incubation with Prazosin 0.01 microM eliminated the F component. Only the S component appeared (with a force equal to that of the previous total response) and it was relaxed by DT by 47 +/- 3%; c) the intracellular Ca pool was depleted by exposure to NE in Ca-free solution + EGTA. Further exposure to Ca = 1.35 mM produced only an S component, which was relaxed by DT by 61 +/- 4%. Since the preceding experiments suggested that the relaxant effect of DT increased as the participation of the Ca pool in the NE response decreased, an intermediate situation was looked for. The Ca pool was depleted as in (c) and then it was partially refilled by brief exposure to Ca = 1.35 mM. DT relaxation decreased to 51 +/- 3% (20 sec of refilling) and to 41 +/- 3% (60 sec of refilling). Similar results were obtained with DT 0.1, 1 and 100 microM. It is concluded that the relaxant action of DT on a NE contraction in rat aorta is inversely related to the amount of NE-releasable intracellular Ca that contributed to that contraction. PMID- 2101547 TI - [San Martin de Porras and psychotherapy]. PMID- 2101548 TI - [Dialectic and psychiatry]. AB - A definition of Dialectics is intended. Its evolution is furthered on--from its originating in the pre-Socratic philosophy up to its culminating with Hegel. Its importance is then postulated for a better understanding of vital history, of endogenous or functional psychoses, as well as classical personality types in their relation with fundamental psychopathological structures. As regards the former, it is the author's contention that dialectical thinking should allow vital history to be understood as the unfolding in time of a consciousness more and more split into increasingly tensioned contradictions until its resolution into either a failure (i.e. disease) or into a synthesis implying a step forward towards maturation, plenitude, or wisdom. As far as endogenous or functional psychoses are concerned, great psychoses could be seen as dialectical polarities, either in themselves (mania v. depression, Crow's Type I v. Type II), or as a group facing another group (v.g. affective diseases v. schizophrenic diseases). What belongs to schizophrenia, and what belongs to depression appear as opposite poles both in previous personality, and the outbreaking situation, both in symptomatology, and evolution. Finally, Dialectics should also allow a conception of the highly classical personality types to be built, and ordered according to polarities (v.g. schizoid-depressive polarity, or hysterical-obsessive polarity) wherein each one may be seen as positive opposite the other one. Deviation towards one of the poles of such alternative need not be considered a deficiency but a dynamic displacement of existence against the opposite pole. A scheme of interrelationship among the aforementioned structures, and psychiatric syndromes likely to be more frequently found is proposed. PMID- 2101549 TI - [An AIDS-related cognitive map in a sample of drug abusers in Buenos Aires City]. AB - This paper is an approach to AIDS as a topic among a drug abusers sample of the city of Buenos Aires. Research was carried out on the basis of a qualitative methodology. In an attempt at surveying opinions and attitudes of such a sample as regards AIDS (i.e. subjects' cognitive map), 21 drug abusers from three different rehabilitation programs operating in the B.A. area were interviewed. On the basis of the research performed, the authors elaborate communication strategies among drug abusers that would be helpful for authorities engaged in AIDS prevention to adopt. To boost a strategy likely to break up the AIDS-drug association existing in the mind of many an abuser would be highly advisable so that a separation be settled between both representations, thus giving drug abusers a higher motivation for self-care practice. PMID- 2101550 TI - [Migration and post-traumatic stress disorders: the case of Mexicans and Central Americans in the United States]. AB - The process of international migration has been associated with increased levels of psychological disturbance and recently investigators have noted the experience of PTSD symptoms among recent war refugees from Southeast Asia. This study sought to first examine the overall impact of migration in a large sample of immigrants from Central America and Mexico in terms of symptoms related to depression, anxiety, somatization and generalized distress. A second aim of the study was to note the existence of specific symptoms related to PTSD diagnoses as related to self-reported reasons for migration. Immigrants were found to have overall higher levels of generalized distress symptoms when compared to non-immigrants, and self reported reasons for migration were highly related to PTSD diagnosis, with 52% of Central American war refugees in this sample meeting the DSM-III criteria for the disorder. Results are discussed in terms of sensitizing mental health professionals to the psychological sequelae of forced migration. PMID- 2101551 TI - [Socioeconomic variables, family milieu, and child mental health in an urban area of Salvador (Bahia), Brazil]. AB - Seeking an association among SEVs, parent's mental health, early family milieu, and children's mental health through an epidemiological survey on a representative 545-child sample from low income squatter population of the city of Salvador was the author's hypothesis. QMPA and QMPI were used to assess the mental health status of parents and children, respectively. A specific questionnaire collected data on social-economic variables, and the HOME inventory was used to measure the quality of stimulation within home environment. For data analysis linear, and multiple regression techniques were resorted to, stratified by children's age and sex as well as parents' working position. In the multiple regression analysis, a strong, significant relationship was found between quality of family environment and indicators of child mental health, consistent throughout all strata analyzed--and even stronger among females involved. Results do not point out a direct influence of parents' mental health, except--in the second set of variables--through the influence of an early family environment. PMID- 2101552 TI - [Medical theory and psychiatry]. AB - The need for a theory is grounded on the heterogeneity of Medicine: Of basic situation, of medical subsystems and of praxis. The relationship between theory and practice in Medicine should be considered as a task of theoretical reflection, beyond contexts, application, and orientation. As a theory of theories--metatheory--its model lies closer to a "science of actions" than a "science of objects", considered as paradigmatic forms of Medicine. The relevance of these concepts to Psychiatry is illustrated on the basis of the influence of behavioral sciences upon biomedicine, whose advancement rests with Psychiatry. PMID- 2101553 TI - [Verbal invention in delusional speech]. AB - In psychotic issues, motor phase of expression is left undamaged: Thus, speech psychotic disorders should imply a disruption of the communication pattern as such. The coining of new words is studied as a paradigm of these disorders. Based on review of theories several authors sustain, the present study intends to outline how verbal invention is likely to appear, as well as the clinical importance of such a finding. The author thus seeks an approach for setting up the concepts of an effective therapy for psychotic patients. PMID- 2101554 TI - [Cultural psychobiology and personality]. PMID- 2101556 TI - [Anorexia. Desire and fear of desire]. PMID- 2101555 TI - [Anorexia nervosa and sexual bulimia (apropos of 8 cases)]. PMID- 2101557 TI - [Sexuality, marriage and family. Values and generations]. PMID- 2101558 TI - [A glance at voyeurism]. PMID- 2101559 TI - [The structural problems of perversion]. PMID- 2101560 TI - [Gender dysphoria and transsexualism. Psychiatric aspects]. PMID- 2101561 TI - [Diagnostic problems of transsexualism]. PMID- 2101562 TI - [Relations between intelligence and perversion. Small essay on ethics]. AB - Excepted vegetarians, everybody let kill and may kill for self-defence. The killed-one suffers and dies. Perversity is to kill or to let suffer without personnal life's saving's necessity--for the treasure of the "perverse subject". We think that such subjects must not be considered as non responsible, excepted when they present a mental retardation. The sexual perversions are probably not the most dangerous: the most are subjects using a personnal high level of intelligence to domination and destruction, including in the sexual behaviours. PMID- 2101563 TI - [Interactions in the alcoholic couple]. PMID- 2101564 TI - [Medicolegal aspects of the psychopathology of sexual behaviors]. PMID- 2101565 TI - [Is there a relation between the symptoms in infants and young children and the modalities of interaction?]. PMID- 2101566 TI - [The emotional climate within the dyad and the individual characteristics of psychological development]. PMID- 2101567 TI - [Anxiety in children in the first 3 months]. PMID- 2101568 TI - [The pregnant adolescent and her infant]. PMID- 2101569 TI - [Perturbations of early interrelations. Maternal pathology and children of risk]. PMID- 2101570 TI - [Interaction and early psychopathology. Anorexia in infants]. PMID- 2101571 TI - [Modalities of early interaction and child development]. PMID- 2101572 TI - [Human ehrlichiosis, a new zoonosis]. AB - Human Ehrlichiosis is a recently discovered zoonosis. It is an infections disease caused by E. canis and transmitted by Rh. sanguineus. Its diagnosis is difficult since the symptoms are non-specific and could be misleading. The IFA Test is the only method for diagnosis. Treatment with tetracyclines gives good results. PMID- 2101573 TI - [Anatomo-clinical study of Madura foot. 8 cases]. PMID- 2101574 TI - [Enzymatic induction with phenobarbital and 3-methylcholanthrene in rats exposed to normobaric oxygen]. AB - Induction by phenobarbital and 3-methylcholanthrene of enzymes metabolizing xenobiotics in rat exposed 55 hrs to hyperoxia, is maintained. The level of microsomal pulmonary and hepatic cytochrome P-450 has even increased. In rat protected against a hyperoxia 6 days, stimulation of UDP-glucuronosyltransferase does not decrease and malondialdehydes level does not change. These results assume the probable role of enzymatic induction in the tolerance to hyperoxia induced in rast by treatment with phenobarbital and 3- methylcholanthrene. PMID- 2101575 TI - [Conjunctival dirofilariasis, a case discovered in the Kairouan region]. AB - A case of conjunctival dirofilariasis was reported in a 55 years old patient, from Kairouan. The human dirofilariasis comes always and only from animals. In most cases, the dirofilariasis is localised under the skin; the ocular localisation of the disease is rare or exceptional. The authors discuss the epidemiology and describe the possible ocular localisation of the dirofilariasis. PMID- 2101576 TI - Cardiomyopathy and pulmonary emboli in terminal Duchennne's muscular dystrophy. PMID- 2101577 TI - Cerebral aspergillosis in liver transplantation. AB - Nine cases of cerebral aspergillosis were identified in a series of 44 brains obtained at necropsy from patients who had undergone liver transplantation. In two of these there was dual infection with Candida albicans. The primary focus of infection was invariably in the lungs. One case of pulmonary Aspergillus infection was found with no evidence of cerebral disease. Infection tended to occur in the period soon after transplantation, was associated with high dose steroids, retransplantation, and showed a significant seasonal incidence. Neurological findings were non-specific and only two cases were diagnosed before death. Aspergillus infection soon after transplantation indicates that this organism is a considerable nosocomial hazard, particularly in the winter and spring months. Positive cultures before death are rarely obtained and antifungal treatment should be started on clinical suspicion alone. PMID- 2101578 TI - Butterfly-shaped mark: a variant form of nevus flammeus simplex. AB - A red-violet, rhomboid-shaped mark on the sacrum of 25 children is described. It is recognized, for the first time, as a part of the nevus flammeus simplex distribution; it is less common than the erythema nuchae or the facial salmon patch. It has the tendency to disappear more slowly than other forms of nevus flammeus simplex. No further investigations seem indicated. PMID- 2101579 TI - Early experience with high thoracic epidural anesthesia in outpatient submuscular breast augmentation. AB - High thoracic epidural anesthesia was administered by anesthetists in 20 patients undergoing submuscular breast augmentation. An average of 12 ml of 2% lidocaine was instilled after sedation with midazolam, 2-6 mg. The augmentation procedure averaged 90 minutes. In 3 patients, the block developed more rapidly on one side than the other, but soon became symmetrical in all; additional subcutaneous infiltration of lidocaine was necessary in 1 patient because of infraclavicular pain; ephedrine, 10 mg was needed in 2 patients to treat hypotension (greater than 20% decrease in blood pressure). Three patients felt infraclavicular pressure; 1 had a brief sensation of breathlessness; 3 had nasal stuffiness from Horner's syndrome associated with the block; none developed headache, back pain, or paresthesias; and 3 had postoperative nausea. The average time from the end of the procedure to patient discharge was 96 minutes. In this limited series, high thoracic epidural anesthesia for submuscular breast augmentation was extremely satisfactory. PMID- 2101580 TI - Captopril renal scintigraphy--an advance in the detection and treatment of renovascular hypertension. AB - Despite the risks associated with renovascular hypertension and the durable benefits of revascularization, the detection of patients with renovascular hypertension and the selection of those who will benefit from interventional therapy remains a challenge. We have previously documented the reliability of captopril renal scintigraphy in predicting angiographically significant renal artery stenosis in patients suspected of having renovascular hypertension. In the present study we report our recent experience with this noninvasive technique in predicting outcome after revascularization. Captopril renal scintigraphy involves the administration of 50 mg of captopril 3 hours after a baseline technitium-99m diethylenetriaminepentaacetic acid renal scan and 1 hour before a repeat captopril renal scintigraphy scan. Nineteen of the last 70 patients with clinically suspected renovascular hypertension undergoing captopril renal scintigraphy had abnormal renal scan outcomes, and 17 had a decrease in flow or function after captopril (positive captopril renal scintigraphy). Eight of these 17 with abnormal findings on captopril renal scintigraphy underwent revascularization, and the hypertension was cured or improved in six of the eight: two of three after surgical bypass grafting and four of five after angioplasty. In the seven surviving patients with abnormal renal scan results but no change with captopril (negative captopril renal scintigraphy), improvement in hypertension after treatment occurred in only one: one of two after nephrectomy, zero of three after bypass surgery, and zero of two after angioplasty (p less than 0.05). We conclude that captopril renal scintigraphy is an accurate predictor of hypertension response to revascularization. Further evaluation of this new noninvasive technique for assessing patients with suspected renovascular hypertension appears warranted. PMID- 2101581 TI - Arteries in contact with the cisternal portion of the facial nerve in autopsy cases: microsurgical anatomy for neurovascular decompression surgery of hemifacial spasm. AB - The cisternal portion of the facial nerve and its contact arteries were examined anatomically in relation to neurovascular decompression surgery to treat hemifacial spasm. Thirty-five sides of brains from 20 autopsied adult patients were examined under a surgical microscope (x 5-x 25). One attaching point was found on 10 facial nerves, two points on 20 nerves, and three points on four nerves. More than two thirds of the facial nerves were attached at two points: the root exit zone and the distal cisternal portion. In a case of distal attachment, the contact artery formed an arterial-nerve complex with the distal portions of the facial and acoustic nerves. The arterial attachment at the root exit zone was evident on 24 of the 35 facial nerves (69%), and most of the contact arteries were the anterior inferior cerebellar artery and its branches. In five nerves, the root exit zone was attached at two points to arteries. The anatomy of autopsied brains without hemifacial spasm is not identical to that of actual clinical cases of hemifacial spasm; nevertheless, the results do aid in intraoperative anatomical orientations. PMID- 2101582 TI - Ventilatory control during exercise in calves with artificial hearts. AB - To determine the role of cardiac reflexes in mediating exercise hyperpnea, we investigated ventilatory responses to treadmill exercise in seven calves with artificial hearts and seven controls. In both groups, the ventilatory responses were adequate for the metabolic demands of the exercise; this resulted in regulation of arterial PCO2 and pH despite the absence of cardiac output increase in the implanted group. In this group, there was a small but significant reduction of arterial PO2 by 4 +/- 3 Torr and a rise of blood lactate by 1.1 +/- 1 mmol/l. When cardiac output was experimentally increased in the implanted calves to a level commensurate with that spontaneously occurring in the control calves, ventilation was not affected. However, experimental reductions of cardiac output led to an immediate augmentation of exercise hyperpnea by 4.56 +/- 4.3 l/min and a further significant lactate increase of 1.2 +/- 1.22 mmol/l that was associated with a significant decrease in the exercise O2 consumption (0.32 +/- 0.13 l/min). These observations indicate that neither cardiac nor hemodynamic effects of increased cardiac output constitute an obligatory cause of exercise hyperpnea in the calf. PMID- 2101583 TI - Assessment of "silent" restenosis and long-term follow-up after successful angioplasty in single vessel coronary artery disease: the value of quantitative exercise electrocardiography and quantitative coronary angiography. AB - Exercise electrocardiographic (ECG) testing during follow-up after coronary angioplasty is widely applied to evaluate the efficacy of angioplasty, even in asymptomatic patients. One hundred forty-one asymptomatic patients without previous myocardial infarction underwent quantitative exercise ECG testing and quantitative coronary angiography 1 to 6 months after successful angioplasty in single vessel coronary artery disease to 1) determine the value of exercise ECG testing to detect "silent" restenosis, and 2) assess the long-term prognostic value of exercise ECG testing and coronary angiography. The prevalence of restenosis (defined as greater than or equal to 50% luminal narrowing at the dilation site) was 12% in this selected study group. Of 26 patients with an abnormal exercise ECG (ST segment depression greater than or equal to 0.1 mV), only 4 (15%) showed recurrence of stenosis. Sensitivity and specificity for detection of restenosis were 24% and 82%, respectively. One hundred thirty-four patients (95%) were followed up 1 to 64 months (mean 35) after exercise ECG testing and coronary angiography. Thirty-two patients (24%) experienced a cardiac event: in 25 patients (78%) the initial event was recurrent angina pectoris (New York Heart Association class III or IV) and in 7 patients (22%) it was myocardial infarction, although cardiac death did not occur. The mean interval between exercise ECG testing and the initial cardiac events was 14 months (range 1 to 55), whereas 47% of the initial events took place less than or equal to 6 months after exercise ECG testing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101584 TI - Sexual assault of men: a series. AB - The case records of five male victims of sexual assault presenting to two genito urinary clinics are presented. The cases were chosen to illustrate the variety of presentations and possible sequelae of sexual assault of adult males. PMID- 2101585 TI - Classification of pressure ulcers. AB - Several systems exist for classifying pressure ulcers, though none of them have been evaluated for interrater reliability. A new grading scale was compared with the commonly used Shea classification. This new scale was developed to provide a more complete description of pressure ulcer healing. The advantages of this scale include a classification of red areas as ulcers to help prevent further deterioration and classification of healed sores to note potential problems. The Yarkony-Kirk scale classifies a red area as a grade 1 ulcer, and involvement of the epidermis and dermis with no subcutaneous fat observed as a grade 2 ulcer. Grade 3 indicates exposed subcutaneous fat with no muscle observed. Exposed muscle without bone involvement is classified as a grade 4 ulcer, and grade 5 describes exposed bone with no joint space involvement. Grade 6 indicates joint space involvement. There is a classification of pressure sore healed to indicate a healed pressure ulcer. Interrater reliability was assessed by two nurses. In spite of an increased number of categories for the Yarkony-Kirk scale, there was no decline in reliability. Reliability was excellent with an interrater correlation of 0.90 for the Yarkony-Kirk scale and 0.86 for the Shea classification when measured for 72 patients. Eighty-five percent of the ratings for the Yarkony-Kirk scale were identical, whereas only 68% were identical for the Shea classification. Three percent of the ratings for the Shea classification were greater than +/- 1 category; 6% of the ratings for the Yarkony-Kirk scale were greater than +/- 1 category. This scale appears to possess good reliability and to describe pressure ulcers more completely. This scale may also be used to teach prevention activities as well as ulcer classification. PMID- 2101586 TI - Life at a price: the implantable defibrillator. PMID- 2101587 TI - Extensive Paget's disease demonstrated on In-111 WBC scanning. PMID- 2101588 TI - A 21-year experience with major hemorrhage after percutaneous liver biopsy. AB - Nine thousand two hundred twelve liver biopsies were performed according to a defined protocol, and data were prospectively recorded to identify risk factors for major bleeding. There were 10 fatal and 22 nonfatal hemorrhages (0.11% and 0.24%, respectively). By comparison with a control group that did not hemorrhage, malignancy, age, sex, and the number of passes were the only predictable risk factors. The risk of fatal hemorrhage in patients with malignancy is estimated to be 0.4%; for nonfatal hemorrhage, 0.57%. In patients undergoing liver biopsy for nonmalignant disease, the risks are 0.04% and 0.16%, respectively. PMID- 2101589 TI - Low fetal risks in pregnancies associated with idiopathic thrombocytopenic purpura. AB - Idiopathic thrombocytopenic purpura and pregnancy are commonly associated. In this article we describe our experience in the management of 61 infants born to 50 mothers with confirmed idiopathic thrombocytopenic purpura. The focus was the neonatal cord platelet count, the parameter of greatest interest to obstetricians. None of the 61 infants had morbidity or mortality as a consequence of the thrombocytopenia. Only three of 61 infants (4.9%) had a cord platelet count that was less than 50 x 10(9) per liter. Although 66% of the infants had a further fall in the platelet count after birth, in all the thrombocytopenia could readily be corrected. Neither maternal platelet count, maternal treatment with corticosteroids, maternal platelet-associated immunoglobulin G level, nor maternal splenectomy could be used to predict neonatal thrombocytopenia. Fetal scalp platelet sampling was likely to lead to an erroneous decision. The rareness of a poor neonatal outcome raises the question of whether obstetric interventions are justified for every pregnant patient with idiopathic thrombocytopenic purpura. PMID- 2101590 TI - The probability of obtaining compatible blood from related directed donors. AB - Patients with alloantibodies may request directed blood donations from their relatives despite the lack of any scientific data suggesting that blood from these donors is safer. We have derived formulas that are applicable to any ethnic group for calculating the probability that a given class of relatives will have compatible blood for a given patient. These formulas apply to any non-X-linked blood group system (including the ABO and Rh systems) and are simple enough for routine blood bank use in advising patients as to how likely they are to obtain compatible donors. Use of these formulas may be helpful in counseling patients who may have difficulty in obtaining compatible directed donors because of antibodies or an unusual blood type. In general, the presence of an alloantibody should not automatically exclude a patient from utilizing directed donors. Moreover, for patients with antibodies to high-incidence antigens, directed donations from siblings may be the easiest way to obtain compatible blood. PMID- 2101591 TI - Reduction in radiation exposure during coronary angiography. AB - In addition to lead shielding, increased distance between the operator and x-ray source will lower radiation exposure. To utilize this principle, we interposed a 24 in. piece of pressure tubing between the catheter used for coronary angiography and the manifold apparatus. Radiation exposure to the hand of the operator during coronary angiography was compared with and without the extension tubing. When corrected for the differences in exposure time, operator exposure was 5.38 mrem/min without the extension and 4.84 mrem/min with the extension. Although this is a small difference in exposure/min, a substantial reduction in exposure could accumulate over a 1 yr period. Insertion of this extension tube into the catheter system is a simple and safe way to further reduce operator exposure during coronary angiography. PMID- 2101592 TI - Treatment of destructive behaviors in persons with developmental disabilities. PMID- 2101593 TI - Blastocystis hominis. PMID- 2101594 TI - Simplified splint construction with light-cured resin. AB - The technique described in this article involves the use of a relatively new material that has reduced the time required for the production of a finished surgical splint to approximately 20 minutes (including the 12-minute curing time of the material). It eliminates exposure to toxic materials, unpleasant odor, skin and mucous membrane irritation, and the myriad of additional time-consuming steps usually required for fabrication of conventional self- or heat-cured acrylic resin splints. The system is inexpensive, compact, nonhazardous, and readily available. PMID- 2101596 TI - Extradural pethidine. PMID- 2101595 TI - The limited potential of special ambulance services in the management of cardiac arrest. AB - For six months a survey was made of all the patients in the Nottingham District Health Authority who died or who were brought to hospital after a cardiac arrest outside hospital. During this period just under half of the emergency ambulance shifts were covered by specially trained crews with defibrillators. During the study period the ICD coding of death certificates indicated that 894 (25%) of the 3575 deaths were due to ischaemic heart disease. During this period the ambulance service received 17,749 emergency calls, which included 445 patients who had cardiac arrests outside hospital. One hundred and forty seven of these patients were carried by ambulances equipped with defibrillators and resuscitation was attempted in 83. Seven patients survived to leave hospital. The special ambulance service was cost effective--a simple calculation suggests that the cost per life saved was approximately 2600 pounds, but it seems unlikely that special ambulance services will materially affect community fatality rates from ischaemic heart disease. PMID- 2101597 TI - Alternative draping technique for claustrophobic patients. PMID- 2101598 TI - Irreducible inguinal hernia in children below two years of age. AB - Eighty-five cases of irreducible inguinal hernia in children below 2 years of age were reviewed. Non-operative treatment was successful in 71 (84 per cent); 14 children required emergency surgery. The younger the child and the longer the duration of symptoms at presentation, the worse was the outcome of non-operative treatment. In 35 (41 per cent) children the diagnosis of inguinal hernia had been made before irreducibility. There is an increased incidence of postoperative complication associated with irreducibility, especially in preterm infants. Early diagnosis of inguinal hernia in young children and prompt referral for surgery is recommended. PMID- 2101600 TI - The hourly wage is an impediment to professional status. PMID- 2101599 TI - Differential expression of CD25 (interleukin-2 receptor) on lamina propria T cells and macrophages in the intestinal lesions in Crohn's disease and ulcerative colitis. AB - Many interleukin-2 receptor (CD25) bearing cells can be identified by alkaline phosphatase immunohistochemistry in the diseased intestinal lamina propria of children with Crohn's disease or ulcerative colitis, but rarely in normal intestine. In both diseases, the CD25+ cells are present as aggregates in the lamina propria below the epithelium, and constitute a large proportion of the lamina propria mononuclear cells. In Crohn's disease, but not ulcerative colitis, CD25+ cells are abundant in the submucosa. The CD25+ cells in Crohn's disease are 58-88% CD3+, CD4+, CD8-, indicating that they are T cells, whereas in ulcerative colitis the CD25+ cells are greater than 80% CD3-, CD4+, HLA-DR+, indicating that they are macrophages. Thus, differential expression of CD25 on T cells and macrophages serves to distinguish the immunologic lesions in ulcerative colitis and Crohn's disease. PMID- 2101601 TI - Sterilising linen thread. PMID- 2101602 TI - [Breast saving operation and adjuvant therapy of breast cancer. Report of the National Institute of Health (NIH) consensus development conference, Washington, D.C., USA, 18-21 June 1990]. PMID- 2101603 TI - Panoramic radiography. PMID- 2101604 TI - [Preventive dentistry in France]. AB - In France, oral prevention has recently progressed in various aspects of dental caries prophylaxis which is reviewed in this paper. A better knowledge of dental caries prevalence has been obtained at a national level and the French Government authorized in October 1985 salt fluoridation for a period of 5 years which in addition to other means of caries prevention such as fluoridated toothpastes and various local and topical procedures has increased the potentials of fluoride use in France. In addition a larger use of fissure sealants has been encouraged. It is hoped that the introduction of salt fluoridation in France will reduce the caries incidence to a DMFT not more than 3 for the 12 year old children thus fulfilling the WHO goals for oral health in the year 2000. PMID- 2101606 TI - [Social security system and preventive dentistry in Grand Duchy of Luxembourg]. PMID- 2101605 TI - [Preventive dentistry in the Federal Republic of Germany]. AB - Caries rates are on the decline in the Federal Republic of Germany, too. And, in some cases considerable, increase in the number of children with caries-free teeth and a clear reduction in the average number of carious teeth has been recorded, above all in kindergartens with preventive dentistry programmes. These results have to be consolidated and expanded upon. A good basis for achieving this would be a standard federal programme in which all the institutions involved would cooperate as partners. PMID- 2101607 TI - [In situ fluoride uptake of initial caries lesions following application of two children's toothpastes]. AB - Cylindrical blocks of enamel with initial caries lesions were brushed twice a day for 6 days using amine fluoride or monofluorophosphate children's toothpaste (250 ppm F-). Some of the enamel samples were left in the oral cavity for three further days after the end of the trial, during which time a fluoride-free toothpaste was used for daily oral hygiene. Half of the enamel blocks showed plaque formation during this period. The other half were kept clean. Fluoride soluble in KOH was only detected on the enamel blocks that had been brushed with amine fluoride children's toothpaste. The amount of solidly bound fluoride was significantly higher following the use of amine fluoride children's toothpaste than with monofluorophosphate children's toothpaste. The amounts of KOH-soluble fluoride and solidly bound fluoride fell again 3 days after discontinuation of fluoride application. But only the drop in the amount of KOH-soluble fluoride in demineralised tooth enamel after application of the two children's toothpastes can be explained by the differing reaction mechanisms of the two fluoride compounds. PMID- 2101608 TI - [Possibilities and limits of application of fluoride-containing varnish in caries prevention, for example, "Fluor-Protector"]. PMID- 2101609 TI - [Influence of eating habits on caries control from viewpoint of prevention research (2)]. AB - The author describes the influence of group standards, primary and secondary socialisation and social class on eating habits, then draws conclusions pertaining to dental health education. PMID- 2101610 TI - [Possibilities and limits of application of fluoride-containing varnish in caries prevention, for example, "Fluor-Protector" (2)]. AB - Using selected literature, the author provides an overview of the possibilities and limits of fluoride varnish application in caries prophylaxis based on the example of Fluor-Protector. He concludes, as did de Bruyn and Arends (1987), that Fluor-Protector is a safe and effective agent that can prevent caries very effectively and is also promising for use as a desensitising substance. PMID- 2101611 TI - [Dental concerns and oral health in population of Greece--future perspectives]. AB - With a profusion of statistical data the authors describe the dental service in Greece, pointing out in particular the difference between the facilities available in the cities and in the country. This is followed by details of the dental insurance system, epidemiological data on the oral health of the population, and examples of prophylactic dentistry. The article concludes with some thoughts on the outlook for the future. PMID- 2101612 TI - [Position of preventive dentistry in Belgium: overview of private and public aspects]. AB - The authors provide a summary of the situation with regard to preventative dental medicine in Belgium, with special emphasis on the health insurance system, the attitude of Belgian dentists to prophylaxis, the status of preventative dentistry at universities, and the estimated requirements with respect to prevention together with some initiatives in this area. PMID- 2101613 TI - [Dental health concerns and advances in preventive dentistry in Great Britain]. AB - The structure, organisation and administration of the National Health Services in the UK including the General Dental Service, the Community Dental Service and the Hospital Service is being described, while emphasising that effective oral health promotion cannot be obtained within the limitations of current organised health services. It demands multidisciplinary and multidepartmental co-work which appears to be beyond traditionally based health services. Dental health education, preventive programmes, epidemiological surveys and dental screening are going to be the main working tasks within the Community Dental Service whereas most dental treatment should be carried out in General Dental Practice. The latter will, in the future, operate as a capitation system rather than fee per-item system with respect to children. Dental health education, water fluoridation as well as the recommendation of fluoride supplements and attempts to reduce sugar intake are key factors in dental prevention in the UK. Some details are given. PMID- 2101614 TI - [Intraoral pH measurement by determination of acidogenic potentials of dietary materials]. AB - The intra-oral production of acid by plaque bacteria from sucrose, glucose and sorbitol and test products with sugar substitutes as well was estimated by pH telemetry which permits the digital registering and collection of data. A pH-drop was not observed when sorbitol or xylitol were offered as a substrate to the dental plaque. The small differences of intensity and duration of the telemetric estimated acid production by dental plaque due to the test products (with sucrose or sorbitol/glucose) exhibited different cariogenic challenge in the animal experiment and in the intra-oral cariogenicity test, but with high probability they have not any practical significance for the preventive dietetic recommendations. PMID- 2101615 TI - [Fluoridation measures and caries prevalence in school children in the former DDR]. AB - Statistical analysis of 3,576 DMFT counts from three million observations of children aged 6 to 16 in East Germany shows a strong time-lagged relationship with fluoridation activities. More significant results, however, are found due to age and a score of socioeconomic factors. Additionally, caries prevalence decreases with time. Conversely, DMFT is not affected by size or type of dental staff, neither absolutely nor relatively. PMID- 2101616 TI - [Oral stereotypes in school children]. AB - When children are asked about school, most say they look forward to it. Not a few children, however, experience feelings of insecurity about school, and in particular starting school. Some are even afraid, and in some cases the child is unable to cope with its fears alone. An orthodontist must reckon with continual or periodical school problems when planning therapy. These difficulties are an essential element of the child's psycho-social world, although by no means the sole element. The relationship between oral stereotypes in school-age children and the necessity of parent counseling or psychological/psychiatric aid for the child is investigated on the basis of clinical reports. PMID- 2101617 TI - [Caries epidemiological study of school children of Rems-Murr area]. AB - An epidemiological study on caries in 1,091 primary school pupils in the Rems Murr area revealed improvement in oral health as compared with results of earlier studies in the Federal Republic of Germany. For example, 31.4% of first-form pupils and 16.1% of fourth-form pupils were shown to have naturally healthy teeth (DMF-T + dmf-t = 0). The average DMF-T(S) values were between 0.39 (0.5) for six year-olds and 2.02 (2.74) for ten-year-olds. The average percent of treated permanent teeth in six (ten)-year-old pupils was determined to be 20.5 (46.5)%. The pronounced polarisation of the individual values is, however, of of ater significance in developing programmes for caries prophylaxis than are these average values: Only 22% of the children accounted for approx. 70% of the carious, missing or filled permanent teeth. Carious defects in the permanent teeth of six and seven-year-old pupils were found almost exclusively in the fissures and pits of the six-year molars. An improvement in the oral health of the above-named age groups can only be achieved by means of specific and individual prophylaxis programmes. PMID- 2101618 TI - [Results of a dental screening of children in five nursery schools in Codogno (MI), in the 1987/88 school year]. AB - Result of a dental screening in the 5 maternal school populations of Codogno (Milan) in the 1987/88 school year. The results of a dental screening performed on 251 pupils from 3 year-old to 5 year-old are reported. The data texted were: oral hygiene degree decayed milk-teeth, decayed permanent teeth, dental and facial anomalies in accordance with WHO classification Geneve 1977. PMID- 2101619 TI - [Correction of a dental and basal Class II with accentuated overjet using traction]. AB - Correction of a dental and basal 2nd class with accentuated overjet using extraoral traction and programmed extractions of 17-27, 38-48 according to Armstrong's technique. The paper reports a case of dental and basal 2nd class with accentuated overjet treated using the extraction of 17-27, 38-48 and extraoral traction only, according to Armstrong's technique. Results obtained after 117 days of combined extraoral traction are reported in order to illustrate the reasons behind the choice of this apparatus and to demonstrate its evident efficacy in this case of 2nd class, 1st subdivision. PMID- 2101620 TI - [Surgical disimpaction and orthodontic repositioning of a retained upper central incisor in the maxilla]. AB - Surgical disinclusion and orthodontic repositioning of superior central incisor retained in the maxillary. A clinical case of inclusion of a permanent central incisor in a nine-year-old patient subjected to combined surgical/orthodontic treatment is reported, the purpose being to demonstrate and confirm the relative simplicity and indisputed advisability of conservative treatment in the case of young patients suffering from dental retention. PMID- 2101621 TI - [Use of a functional appliance in initial orthodontic treatment of a case of dental and basal Class II with dental biprotrusion at age 12]. AB - Use of functional plaque in the initial orthodontic treatment of a case of dental and basal 2nd class with dual dental protrusions in a 12-year-old patient. The use of a functional plaque is described in a 12-year-old male patient in dental and basal 2nd class, following the extraction of 1.6-2.5-2.6-3.6-4.6 due to caries. Biprotrusion was observed together with an overjet of 8 mm and an overbite of 6 mm. Results of the therapy are reported after 21 months. PMID- 2101622 TI - [Classification and etiopathogenesis of upper canine impaction]. AB - Classification and aetiopathogenesis of upper canine inclusion. The possible causes of upper canine inclusions are reviewed. After a detailed description of the factors that generally contribute to determining inclusions, it is stressed that correct aetiopathogenetic classification of this pathology can contribute to making the complex protocol for its treatment easier. PMID- 2101623 TI - [A case of tooth retention with malformation of indirect traumatic origin]. AB - A case of dental retention following malformation originating from an indirect injury The paper reports a case of retention and malformation of the permanent dental buds following a traumatic event in infancy, which was resolved using dental therapy. PMID- 2101624 TI - Setting a practice style. AB - Creating a corporate image is a subject that many companies will spend amazing amounts of time and money getting right, yet is often totally ignored by the small business or professional. In the third article in his series Andy looks at how the general practitioner can (and should) give serious thought to this topic before allowing other more immediate matters to overwhelm his attention. PMID- 2101625 TI - What your computer can do for you. AB - There is no doubt that any improvement in practice efficiency should release valuable time for both the dentist and staff to enable them to look after patients. Computers are thus an obvious subject to include in Dentessence because they can improve efficiency. Yet so often all computers seem to do is increase work rather than decrease it. One practice that enthuses about their computer belongs to Robin Denville, who has found that when used correctly and backed up effectively a computer plays a significant role in helping the practice provide the kind of service that the patients want. So we asked Chrissie, Robin's wife and practice manager, to write this article as a first in what we hope will be an irregular series on the value of the computer in today's marketplace. PMID- 2101626 TI - Caring calls. AB - Alison has looked into how to set up a system to follow up your patients on the telephone following a difficult extraction or extensive restoration. The secret is that it is easy if you follow a careful and well thought out system, such as the one described in this article. PMID- 2101627 TI - Dealing with the dilemma. AB - When we first thought of this series we agreed that there was one man who could do justice to the main theme of the series - the actual dilemma many new graduates face immediately on going into general practice. So we approached Colin Dexter and asked him if he would write our introductory article. But, like many creative people, Colin's hectic timetable meant we had to wait for his thesis. And thesis it turned out to be. But, despite the wait and the length of his article, we feel we have a superb example in words of the true dilemma that so many people experience, and so many authorities try to deny. So settle down for a thought-provoking and stimulating read... PMID- 2101629 TI - Expression of a class I MHC transgene: regulation by a tissue-specific negative regulatory DNA sequence element. AB - In vivo patterns of expression of a miniature swine class I major histocompatibility gene, PD7, were analyzed both in situ in the pig, and in transgenic mice. Structural analysis of PD7 DNA sequences revealed that PD7 is highly homologous to the pig gene PD1, which encodes a classical transplantation antigen. Despite the extensive homology, PD7 is expressed in situ at markedly lower levels than PD1 in nearly all tissues. Introduction of PD7 into mice results in a pattern of PD7 expression in the transgenic animals that parallels that observed in situ in the pig. Comparison of two lines of PD7 transgenic mice, which differ only in the extent of 5' flanking sequence, reveals the presence of a silencer element. The silencer activity is tissue specific: differences in PD7 expression are observed only in lymphoid tissues and skin. Skin from both lines of transgenics mediates graft rejection, but the rate of rejection correlates with the level of PD7 expression. PMID- 2101628 TI - Insertional inactivation of the p53 gene during friend leukemia: a new strategy for identifying tumor suppressor genes. AB - Rearrangements within the p53 gene are observed in a high proportion of independent erythroleukemic cell lines derived from the spleens of mice infected with Friend leukemia virus. The majority of cells with at least one rearranged p53 allele do not express detectable levels of p53 protein. Here, we show that in 4 out of 19 newly established erythroleukemic cell lines induced by infecting DBA mice with either the anemia (FV-A) or polycythemia (FV-P)-inducing strains of Friend virus, the p53 gene is rearranged as a result of integration of spleen focus-forming virus (SFFV). Integration of SFFV within the p53 gene resulted in inactivation of gene expression as determined by Western blot analysis. The sites of SFFV integration in the p53 gene were found, by Southern blot analysis and the polymerase chain reaction, to be localized in a 1-kbp region between introns 7 and 9. In addition, loss of the normal p53 allele was observed in three of the erythroleukemic cell lines that carried a rearranged p53 gene. Insertion of SFFV in these cell lines resulted in either the appearance of aberrant p53 transcripts or the complete lack of p53 expression. The results presented in this paper demonstrate that retroviral insertions can not only contribute to neoplastic transformation by activating dominant oncogenes but also by inactivating genes that normally function in a negative way to control cell growth. Thus, it may be possible to identify additional genes of this class by characterizing chromosomal sequences that are adjacent to common sites of retroviral integration in tumors. PMID- 2101631 TI - Support for the new biology in an integrated Europe. PMID- 2101630 TI - Induction of nuclear NF-kappa B DNA binding activity after exposure of lymphoid cells to soluble tax1 protein. AB - We demonstrate that purified HTLV-I Tax1 protein can be taken up by 70Z/3 lymphoid cells and localized in both the nuclear and cytoplasmic compartments. Introduction of the Tax1 protein into the growth medium of 70Z/3 cells resulted in the rapid and transient induction of NF-kappa B binding activity in the nuclear fraction. Tax1 activation of NF-kappa B was not sensitive to either staurosporin or prolonged stimulation with the phorbol ester 12-O tetradecanoylphorbol-13-acetate, suggesting that Tax1-dependent NF-kappa B activation did not require the protein kinase C pathway. Purified Tax1 did not directly increase NF-kappa B binding activity in 70Z/3 cytoplasmic extracts, suggesting that NF-kappa B induction may require cellular factors. Western blot and competitive radioimmunoassays demonstrated that Tax1 protein was present in the tissue culture media of HTLV-I-transformed cell lines. These results show that extracellular Tax1 may regulate cellular gene expression in noninfected cells. PMID- 2101632 TI - From gene to chromosome: organization levels defined by the interplay of transcription and replication in vertebrates. AB - In higher eukaryotes, gene activation is accompanied by an increased sensitivity to DNaseI over a domain that extends beyond the limits of the gene itself, or of the gene cluster to which it belongs. This increased sensitivity probably reflects both the partial decondensation of chromatin and an increased communication with the outside of the nucleus. In addition, gene activation usually causes a coreplication domain that extends much beyond the decondensation domain to switch to an early replication time in S phase. This switch is produced, at least in some cases, by an early firing of origins of replication situated in flanking condensed chromatin. Some of the recently identified DNA domains that tether chromosomal loops to the nuclear matrix do represent the borders of decondensation domains. They may also constitute pausing sites for replication forks. The different replication times of successive 200- to 400-kb regions along the genome may have been the basis for the observed long-term differentiation of very large genomes in domains of different overall sequence composition (G:C content and distribution of short repeated motifs). Chromosomal bands represent a low resolution picture of this pattern. Just like gene methylation, differential replication timing and the consequent compositional differentiation of the genome have probably contributed to making the management of very large genomes workable. PMID- 2101633 TI - The hok killer gene family in gram-negative bacteria. AB - The seven members of the hok killer gene family in Gram-negative bacteria are described here. The members of this gene family have been sequenced and include hok/sok from plasmid R1, flm and srnB from plasmid F, pnd from plasmids R483 and R16, and gef and relF, which are located on the Escherichia coli chromosome. The killer proteins encoded by these loci are highly toxic polypeptides of 50 to 52 amino acids. The proteins kill the cells from the inside by interfering with a vital function in the cell membrane. On the basis of their relatedness, the killer proteins and their corresponding loci are divided into four subfamilies. The members of one subfamily, hok/sok and flm, mediate plasmid maintenance by killing plasmid-free cells. The pnd and srnB subfamilies were discovered through their abilities to cause membrane damage and degradation of stable RNA. gef and relF, which constitute the chromosomal subfamily, were found because of their sequence similarity at the DNA and protein levels with other members of the hok gene family. However, no function has been described for the proteins belonging to this subfamily. Although the four subfamilies are distantly related in terms of DNA and protein sequence similarity, the overall genetic organization of the different loci has been well conserved during evolution. The expression of all of the members of the hok gene family is regulated post-transcriptionally. Thus, the expression of the hok and flm genes is regulated by small antisense RNAs that inhibit the translation of the stable hok and flm mRNAs. On the basis of structural and functional similarities, we suggest that each of the related plasmid-encoded killer genes is regulated by antisense RNAs. The conservation of this widespread gene family in Gram-negative bacteria suggests that the genes are important to the genomes that carry them. PMID- 2101634 TI - [Pulmonary hydatid cyst. Presentation of a case]. AB - One case of pulmonary hydatid cyst from Venezuela is reported. A 54-year-old man from Syria, was admitted to the hospital because of dyspnoea, fever and weight loss. A thoracic roentgenogram revealed a tumor in the basis of the left lung; a lobectomy was carried out. Histological study showed an unilocular hydatid cyst. The presence of scolices in alveoli and vessels suggest a probable dissemination of the parasite. Due to the rarity of the pulmonary hydatid cyst in Venezuela, the case is reported to call the attention about the existence of this pathology in the country, so that it can be diagnosed and treated correctly. PMID- 2101635 TI - [Hyperinfectious and disseminated strongyloidiasis in underdeveloped countries]. PMID- 2101636 TI - [Fatal hyperinfectious strongyloidiasis: report of 3 cases]. AB - The present paper reports three fatal cases of massive strongyloidiasis. Case 1. A 37-year-old woman with a record of arthropathy and corticosteroids treatment, died in shock. The postmortem examination showed massive intestinal strongyloidiasis with larvae dissemination to lungs, liver, spleen and the adipose tissue located around adrenal glands. Case 2. A 12-year-old, malnourished girl died of peritonitis. The autopsy findings were lithiasis and perforation of jejunum, hyperinfectious strongyloidiasis of intestines and lungs, acute and chronic peritonitis. Case 3. A 7-year-old, cachectic girl with corticosteroid therapy, died in cardiorespiratory arrest. The autopsy revealed hyperinfection by S. stercoralis affecting stomach, intestines, lungs, liver and brain. In Venezuela, literature on massive strongyloidiasis is scarce. The present report stresses the importance of considering this syndrome in patients at risk, in endemic areas, like Venezuela, to prevent unnecessary deaths. PMID- 2101637 TI - [Antibodies against Venezuelan equine encephalitis in the human population of the Mara district of the state of Zulia, Venezuela]. AB - Antibodies against Venezuelan Equine Encephalitis Virus (VEEV) were studied in the human population of Mara District, Zulia State, Venezuela. Two hundred thirty nine blood samples were taken from the towns of San Rafael de Mara, Santa Cruz de Mara, La Sierrita-4 Bocas, Carrasquero, Isla de San Carlos e Isla de Toas, during june, july and september, 1988. Donors samples were classified by age, sex and serological titres. Eighty nine were less than 15 years old (37.2%) and 150, over 15 years old (62.7%). From the 239 samples, 224 were negative (93.7%) and 15 positive (6.3%). Our results indicate that must of the population from the studied towns were negative for VEEV antibodies and being exposed to the disease. PMID- 2101638 TI - [Incidence of Chlamydia trachomatis in patients with sterility]. AB - Eighty six women were studied at the Hospital Chiquinquira in order to determine the role of Chlamydia Trachomatis in infertility. Endocervical samples were taken in 45 infertile women (IG) who concurred to our Gynecologic Endocrinology Clinic and in 41 (CG) who sought medical attention at our General Gynecology Clinic for different reasons. The Chlamydiazyme Test (CT) was performed in all of them. We obtained 12 positive Chlamydiazymes (13.95%), four of them were in the IG (8.89%) and 8 (19.5%) in the CG; this was not statistically significant (p = 0.3). We also found no correlations when positive tests were correlated with sterility (p = 0.5, tube pathology history (p = 0.2), HSG (p = 0.2) and laparoscopic findings (p = 0.1). We did not find an increase in the occurrence of CT in our infertile women as reported by other authors therefore its significance in our study group at this time is uncertain. PMID- 2101639 TI - [Tetracycline and AIDS]. PMID- 2101640 TI - [Effect of temperature and humidity on the frequency of pityriasis versicolor. Epidemiological study in the state of Falcon, Venezuela]. AB - The survey covers 1546 people from three towns of Falcon, which present different climatological characteristics. The diagnostic of P.V. was confirmed through microscopic observation. It is demonstrated a notable increase of the frequency of P.V. during and after the puberty. Significative differences were found between the frequencies of P.V. in the semiarid zone (9%) and the sub-humid zone (12%). The lowest frequency (4%) corresponds to the temperate climate of La Sierra de Falcon. The study shows, for the first time, that a hot and humid climate favors the parasitism by Malassezia sp. PMID- 2101641 TI - Allergic and nonallergic rhinitis: their characterization in a tropical environment. AB - The differences between allergic and non-allergic rhinitis were evaluated in 127 individuals from tropical urban region of Venezuela. The study design had historic data obtained regarding exacerbation of initial symptoms on exposure to common precipitants, physical examination, nasal cytology, immunodiagnostic test, routine laboratory test (fresh stool test, white cell count and urine test) and sinus x-rays. Forty nine patients were diagnosed as having allergic rhinitis (AR), 10 as probably having AR, 13 had infectious rhinitis, 4 had mixed components, 1 as non-allergic non-eosinophilic rhinitis, and 50 had no evidence of immunological nasal respiratory allergy and were taken as controls. The associated findings with allergic rhinitis were: conjunctivitis 62%, sinusitis 23%, and bronchial asthma 24%. Our results support a significative prevalence of allergic rhinitis in this particular group, with similar symptom patterns to that of industrialized countries. PMID- 2101642 TI - [Metabolic changes and most frequent complications in a group of type II diabetics. Their relation to the hyperglycemic state]. AB - With the purpose of knowing which metabolic disorders and clinical complications are more frequently developed by diabetic patients, and to analyze the relationship between the hyperglycemia state and appearance of these complications, we studied a group of patients from a Metabolic Diseases Clinic in Maracaibo, Venezuela. Fifty-four Type II diabetics patients were evaluated by means of: physical examination, anthropometric measurements, biochemical control of glycemia, insulin and lipid pattern, as well as evaluation of the complications presented. The sample consisted of 33 men and 21 women, 75% of which had glycemic values over 140 mg/dl. Basal insulin values were significantly high (29.9 +/- 8.3 uU/ml in men and 30.9 +/- 10.1 uU/ml in women) in relation to a control group (14.5 +/- 2.4 uU/ml), concluding that our diabetics presented basal hyperinsulinemia and insulin resistance. The lipid pattern of the subjects studied showed hypertriglyceridemia (70%) and hypercholesterolemia (67%). A positive association between glycemia and triglycerides values was found in the total group. HDL-cholesterol values were significantly lower in relation to the control group, obtaining a negative correlation between HDL-cholesterol and triglycerides. The clinical complications observed in these diabetics were: non specific visuals alterations, signs of arterial illness and sensorial disorders distributed in a similar percentage (63, 61 and 51%, respectively). When the independence test X2 was applied, we obtained association (p less than 0.05) between glycemia and the frequency of complications. PMID- 2101643 TI - [Granular CALLA-positive acute lymphoblastic leukemia]. AB - One of the main criteria in the differentiation between acute lymphoblastic (ALL) and acute myeloblastic leukemias (AML) is the presence of granules in the blasts of the latter. Recently, several groups have described a form of ALL with prominent intracytoplasmatic granules (G-ALL) in the blasts. The granules in the G-ALL blasts do not contain myeloperoxidase, but sometimes have lipids that stain with Sudan black B (SBB). We describe a case of G-ALL in a five-year-old girl whose peripheral blood and bone marrow was compound of 98% lymphoblasts, 30% of which, had prominent azurophilic intracytoplasmatic granules. The granules did not have peroxidase, acid phosphatase, varies; is directly proportional to naphthyl acetate esterase. However 5% of the blasts had sudanophilic granules and 60% were positive for the periodic acid-Schiff reaction. The blasts expressed the CD10 (CALLA) and Dr antigens, and were negative for surface immunoglobulins or the CD4, CD8, or CD14, antigens. Only 18% of cells formed rosettes with sheep erythrocytes. The patient responded to vincristine, prednisone and L asparaginase. Based on the finding we diagnosed this as a CALLA positive G-ALL. By conventional criteria this case would have been wrongly classified as AML. PMID- 2101644 TI - [An evaluation of appliance hygiene index on patients wearing removable orthodontic appliance]. AB - The appliance hygiene performance and its relationship with stomatitis lesions were investigated on 124 patients who were using maxillary removable orthodontic appliance. The patients were divided into five groups according to the appliance wearing periods. Appliance hygiene index (AHI) showed no significant difference between the groups except the fifth group and the prevalence of stomatitis was found as 8.9 percent. There was not any significant correlation between the quantity of plaque and the degree of stomatitis. PMID- 2101645 TI - [Evaluation of the head posture in orthodontic malocclusions]. AB - Recently the effect of the head posture on craniofacial and dentoalveolar morphology had been an interesting research topic. Head posture was defined as the craniovertical angle formed between the head in self-balanced position and the true vertical. A foreward bending deviation of the head was termed flexion, and a backward bending deviation of the head was termed extension. In this study, total of 60 subjects with Angle class 1, class II/1 and class III malocclusion, who did not have orthodontic treatment previously and who did not have any sight or nose breathing problems, without vertical discrepancies like openbite or extreme deep bite had been chosen. Craniovertical angle which determined the posture of the head had been measured directly from the individuals. We found a statistically significant relationship between the head posture, class II/1 and class III malocclusions. PMID- 2101646 TI - [Development of functional jaw orthopedics and function regulator]. AB - Functional jaw orthopedics is an orthodontic treatment which uses muscle stimuli developed from the functions and tonus changes of masticatory, tongue, lip and cheek muscles. The functional regulator which is one of the appliances used in this treatment, takes support not from the teeth, but directly from the soft tissues in order to make changes in alveolar bone and teeth. PMID- 2101647 TI - [Orthodontic treatment in a cleft palate-cleft lip case with severe maxillary collapse]. AB - The cleft lip and palate cases are the most frequently seen congenital deformities. Retardation of the maxillary development and collapse are the most significant characteristics in these cases. It is aimed to correct the functions like mastication, deglutition and speech which were disturbed due to anatomic deficiency and to obtain an acceptable occlusion and esthetics, by means of the therapy. As much as the preoperative orthopedic procedures applied just after the birth, the orthopedic and orthodontic appliances used in mixed and permanent dentition periods affect the prognosis in these cases. The purpose of the treatment in permanent dentition is to correct the malocclusion and to prepare the dentition to prosthetic restorations. In this article the orthodontic treatment of a case in permanent dentition, with cleft palate and lip characterized with severe maxillary collapse will be presented. PMID- 2101648 TI - [Begg mechanics in treatment of congenitally missing lateral incisor]. AB - The maxillary lateral incisors are the most frequently missing teeth after the third molars. The cases with congenitally missing lateral incisors are treated either by orthodontically closing the spaces or by space regaining for prosthetic restorations. Malocclusion is the most effective factor for selecting the treatment method. Besides the characteristics of the malocclusion and interdigitation, the colour, the shape, the size and the position of the canines effect the treatment planning. In particular, Class II Div. 1 and Cl. I anterior crowding cases are the most convenient cases for orthodontically closing the missing lateral spaces. In these cases besides the treatment of the present malocclusion the reshaping of the canines is aimed and these teeth are moved to lateral spaces. In this article the treatment of a Cl. II Div. 1 malocclusion case with congenitally maxillary missing lateral incisor with Begg technique will be presented. The changes and variations of the Begg mechanics applied for this case will be discussed. PMID- 2101649 TI - [The occurrence of cavitation after orthodontic bonding. A case report]. AB - In this case report occurrence of cavitation on the lingual enamel surfaces of teeth after orthodontic direct bonding a canine to canine lingual retainer is presented and possible reasons which might play a role in their formation was investigated by "SEM" and "electron microprobe analyzer". Although the morphologic structure is normal, a mineral loss is detected and it is thought that an easier dissolution of enamel is occurred by the penetration of saliva and plaque microorganisms throughout the enamel-resin junction. PMID- 2101650 TI - [The treatment of cross-bites in the Angle Class I cases with modular 3 D lingual appliances]. AB - Anterior cross-bites which involve one tooth or a group of teeth is commonly seen in every age groups. Removable or fixed appliances are used in the treatment of these cases. Both of these appliances have some advantages and disadvantages. The objective of this study is to evaluate the effectiveness of the Modular 3 D Adapter in the treatment of the anterior cross-bites. All of the 14 patients aged between 10 years 1 month and 24 years 2 months showed Angle Class I anterior Cross-bite malocclusion. Only the first molar tooth or teeth were banded, then 0.025 inch Adapter appliance was used Lingually. By applying a force between 60 70 grams, the normal occlusions were gained after 2 months. PMID- 2101651 TI - [Examination of the effects of various orthodontic appliances on periodontal tissues]. AB - This study has been planned to examine the effects of various orthodontic appliances on periodontal tissues and the effect of motivation from the point of oral hygiene during the usage period of these appliances. 45 individuals; 15 of them using removable appliances, 15 of them using fixed-DBS appliances and 15 of the patients treating with fixed-multiband technics, have been used. In the beginning; the pocket depths, gingival and plaque indices of all cases have been reported and then they were motivated for their oral hygiene. The measurements were repeated for each of the motivated cases after 1 month. Statistically significant difference was found only in pocket depth between the 3 groups. There were statistically significant differences in pocket depth, gingival and plaque indices values in each of the groups before and after motivation. PMID- 2101652 TI - [The functional regulator (FR I)]. AB - The FR I appliance, which aims the sagittal, vertical and transversal development of intraoral cavity by keeping away the perioral muscles is used widely in crowded Angle Class I and Class II Division 1 cases. The most active period for Frankel I treatment is the time upper and lower incisors finish their eruption and the posterior deciduous teeth are in their places only for retention. In the 11 year old patient treated with FR I appliance for 6 months, the ANB angle decreased by 3.5 degrees and an anterior development of mandible was established. Also a transversal development in lower and upper jaws and sagittal development in the lower jaw were seen. PMID- 2101653 TI - [The functional regulator (FR II)]. AB - The Frankel II appliance which is used in Angle Class II Division 2 cases, establish sagittal, vertical and transversal development of the jaws by keeping away the perioral muscles as in the other functional regulators. The difference between FR II and FR I appliances is the design of canine wires. After 8 months of FR II treatment of the 11 year old Class II Div. 2 patient with 5 mm. overbite, as the overbite decreased by 3 mm., the FMA angle increased and a transversal and sagittal development was established in both upper and lower jaws. PMID- 2101654 TI - [The functional regulators (FR III, FR IV)]. AB - The Frankel III appliance is used in Angle Class III, maxillary deficiency cases. The vestibular and buccal shilts changes the sagittal relationship of the jaws in Class III cases by developing the upper jaw sagittally, vertically and transversally. After 7 months of FR III treatment of an 11 year old Class III patient, the molar relationship and anterior crossbite were corrected. As the SNA angle increased, the -2 degrees ANB an le changed to 2 degrees. As there were no transversal and sagittal development in lower jaw, the upper jaw expanded transversally and sagittally. Also the FR IV appliance is used in the treatment of open-bite and bimaxillary protrusion cases. PMID- 2101655 TI - [Alopecia areata is an idiopathic disorder in which there is a rapidly developing loss of hair that usually begins on the scalp]. AB - In this article a case of alopecia areata which developed due to combined headgear is presented. It is aimed to warn the orthodontists about this rarely seen adverse effect of the extraoral orthodontic appliances. PMID- 2101656 TI - [Long-term evaluation of the periodontal status in extraction treatment]. AB - In this article the periodontal status of the 30 patients which were treated with Edgewise mechanics, by extraction of four first bicuspids is evaluated approximately 5 years later the active treatment. Comparison of the pocket depths between the teeth moved into extraction areas and the other teeth, is made. And also the pocket depths of the parallel and non-parallel teeth in the extraction area are compared. It is found that orthodontic treatment had no adverse effect on periodontal status in long term. But non-parallel teeth in the extraction area showed much higher values of pocket depth when compared to parallel teeth. PMID- 2101657 TI - [The study of the relationship between the face type and condyle morphology (a cephalometric and anthropometric study)]. AB - The main purpose of this investigation was to study the shape and size of the mandibular condyles for any correlation with type of mandibular rotation. 40 mandibular bones that belongs to modern man, and late Roman stage were examined regarding the size and shape of condyles. The cephalograms of the mandibles were taken and the type of mandibular rotation was recorded on them according to Leiba analysis. The Leiba analysis results showed statistically significant differences while, the differences between the condyle sizes were found to be insignificant between the groups. PMID- 2101658 TI - [Investigation of pre- and post-treatment cephalometric measurements of the subjects treated by Edgewise technique]. AB - In this study, pre and posttreatment cephalometric measurements of twenty-four cases, of which twelve had Angle Class I and twelve had Angle Class II, division 1 malocclusion were studied. Dental, skeletal and soft tissue changes were observed in both class I and class II, 1 malocclusions treated by Edgewise Technique with extraction. PMID- 2101659 TI - [Investigation of the effect of functional treatment in skeletal Class III cases on the profile facial esthetics]. AB - In this study, effects of chin-cap therapy on profile facial esthetics were investigated. 30 patients indicating skeletal and dental Cl III anomalies were divided into two groups. The first group, including 21 patients with the average age of 11 was treated by chin-cap therapy, average treatment time being 0.7 years. This group involved 10 females and 11 males. The second group involved 9 persons, 5 females and 4 males, with the average age of 9.7, average control period being 2 years. The investigation was carried out on the 60 lateral cephalometric films taken from both groups. 2 angular and 9 soft tissue cephalometric measurements were made on each film. The comparisons between the groups indicated that the treatment affected the soft tissue measurements positively. PMID- 2101660 TI - [The effect of growth and development on soft tissue profile in boys and girls with normal occlusion]. AB - In this study the effect of the growth and development on soft tissue profile of preadolescent subjects with normal occlusion, skeletal class 1 and mesiodivergent structure was investigated. 10 girls, the mean skeletal age being 9.28 +/- 1.58 years and 10 boys, the mean skeletal age being 9.88 +/- 1.80 years were selected. Two standardized lateral cephalometric roentgenographs were taken from all subjects at one year interval. The angular and linear measurements were performed on tracing films. The mean values of these measurements were calculated and statistically evaluated. According to statistical evaluation, the growth and development of the lips and soft tissue chin in both girls and boys were normal and they were in harmony with each other. However in girls the increase of lower lip thickness and in boys the changes of hard and soft tissue pogonion positions were found to be statistically insignificant. In girls, the correlations between the upper lip position and maxillary growth. PMID- 2101661 TI - [Effects of lower canine distalization with sectional arches on the positions of lower incisors and molars]. AB - The purpose of the study was to investigate the effects of lower canine distalization with .016 x 0.016 inch sectional arches on the positions of lower incisors and first permanent molars. Study was carried out on two lateral cephalograms taken at the beginning of treatment and at the end of canine distalization over a period of six months, from each of 17 subjects having a chronological age range of 11 years 8 months and 19 years and whose treatments with first premolar extraction were begun with .018 inch slot std. edgewise technique. Due to the mean lower canine distalization of 3 mm. till spacing of lower anteriors, mean lower incisor retrusion of 0.9 mm. concurrent with a mean decrease of 0.9 mm. in Holdaway difference were occurred which were both found to be statistically significant. Mesial movement of lower first permanent molars having a mean of 0.3 mm was not found to be significant. PMID- 2101662 TI - [Mandibular values in adults with normal occlusion]. AB - This study was done to find out the standard norms and their relations in the mandibular dimensions and angles in cephalometric x-rays of total 85 adults-48 males and 37 females-aged 18-20 with normal occlusion. The dimensions of ramus and corpus with the lengths Co-Go and Go-M lines and effective mandibular lengths with Co-Pg and also the Co, Go and M angles were measured by cephalometric rules. The mean values, standard deviations and the correlation coefficient of these measurements were evaluated statistically and the values related to mandibular with normal occlusion in both sexes were shown. Ramus-total relations in males and corpus-total relations in females and relations of all mandibular angles in both sexes were found significant in the individuals with normal dental occlusion and skeletal pattern. PMID- 2101663 TI - [Comparison of lower incisor positions after treatment and in postretention period, in Cl. I cases treated with Begg and Edgewise techniques]. AB - The lower incisor positions have an important role in obtaining optimum occlusion and esthetics with orthodontic therapy. The aim of this study is to evaluate in longterm, the lower incisor positions of class I anterior crowding cases which were treated with Begg and Edge wise techniques. For this purpose lateral cephalometric radiographs of 20 Edge wise and 11 Begg cases which were treated by extraction of the four first bicuspids are evaluated. In all the cases T to NB (mm) T to NB (angle) and IMPA parameters examined before treatment, just after active therapy and in an average of 5 years postretention period. In cases which were treated with Begg mechanics, statistically important improvement is found in IMPA values after treatment. Lower incisors were stable in postretention period and there were no statistically significant differences when we compared the "after treatment" and "postretention" incisor positions in both treatment groups. PMID- 2101664 TI - [Comparison between the individuals of our society which have NOTR occlusion and Bjork norms]. AB - In this study, tele radiographs of 52 military academy students neutral occlusion were taken in order to establish the deep facial structure standards of our society. Anterior and posterior lengths of cranial base, ramus height and mandibular length were measured from the cephalometric lines of these pictures. Likewise, measurements were made of Cella, Articular and Gonion angles. Average values, standard deviations and errors were obtained of all these results. These measurements were compared through biometric methods with those previously made by Bjork. The anterior and posterior lengths and the ramus height show biometrically insignificant differences in these two studies. The same also applies for the Cella and Articular angles. On the other hand, the ramus height which we determined is somewhat greater and significantly different from that of Bjork from the biometrical viewpoint. Furthermore, our Gonion angle is less than that of Bjork, and significantly different from the biometrical standpoint. In conclusion, it is suggested that the Ramus height and Gonion angle found through our study should be utilized for our purposes in all dental interventions to be made on the individuals of this society. PMID- 2101665 TI - [A cephalometric comparison of maxillary and mandibular incisor teeth position and soft tissue profile]. AB - In this study which is done to examine the effect of teeth positions on soft tissue profile (45 males-age 20-and 20 females age average 18.2 +/- 0.58) total 65 adults with normal orthodontic region, what the position and thickness of soft tissues should be is shown when the teeth are in normal occlusion. In this research which puts for the certain dentofacial criteria, dental system with soft tissue positions and thickness in both sexes is important. When lower and upper lips are tangents to or just behind Steiner's "S plane" the balanced facial profile in our population is found and considered to be ideal statistically. In spite of this the criteria used esthetic balances changes from one person to another. PMID- 2101666 TI - [A cephalometric comparison of skeletal profile and soft tissue profile on adults with normal occlusion]. AB - This study is realized to correlate skeletal and soft tissue profiles cephalometrically on (45 males - age 20 and 20 females-average chronological age 18.2 +/- 0.58) total 65 adults with normal occlusion. For skeletal analysis GoGnSN, SNA, SNB, ANB angles and convexite and face angles which are accepted as the certain commune characteristics of profile are measured as well. Lower and upper lip positions were determined according to Steiner's "S plane" on individuals with normal dental occlusion and skeletal pattern. Having drawn soft profile and perpendicular to face plane (Na-Pg) from the tips of lips, chin and nose, thicknesses of soft tissue are measured. The mean values obtained, standard deviations and correlation coefficients were evaluated by using Systat package program. Relationships between the convexite angles and soft tissue thickness are found significant on males and lip positions and soft tissue relationships on both sexes are found meaningful. PMID- 2101667 TI - [EMG investigation on mentalis, masseter and OOS muscles of adults with Class III malocclusion]. AB - In this study mean amplitude values obtained from mentalis, Masseter and OOS muscles electromyographic records of adults with normal occlusion and with Class III malocclusion were compared. As regards to Class III malocclusion, it was determined that mean amplitude values decrease and enough interference could not be formed due to the hypofunction of mentalis muscle related to mandibular protrusion and increase in low face height. There was no significant differences between normal and Class III malocclusion cases for the masseter muscle. Decrease of mean amplitude values were observed for the OOS muscle it was not showing maximal contraction due to the its hypofunction. PMID- 2101668 TI - [Treatment of Angle Class II/1 malocclusions with the Herbst appliance]. AB - In this study 10 Angle class 11/1 cases who did not complete their maximal pubertal development, with retrognathic mandible and deep bite were treated with the Herbst appliance. Together with significant dental, skeletal and soft tissue changes, Angle class 1 occlusion was achieved. Normal function and esthetic appearance were established. Lateral radiographies of pre-treatment, post treatment and retention periods were evaluated. Skeletal and dental factors contributing to the establishment of class 1 occlusion were determined. PMID- 2101669 TI - Training in cytopathology. PMID- 2101670 TI - Effect of regular 3-yearly screening on the incidence of cervical smears: the Leiden experience. AB - The effect of regular 3-yearly screening over a period of 12 years, on the incidence of cervical cancer in 25,000 women aged 35-54 years, is examined. The rate of squamous cell carcinoma decreased from 0.38 per 1000 women in the first round to zero in the fourth round. Similarly, the rate of carcinoma in situ declined from 1.69 per 1000 women in the first round to 0.35 per 1000 in the fourth round. The rates of severe dysplasia showed no decline. Cytologic under diagnosis of carcinoma-in-situ and cervical carcinoma increased with each round. Widowed and divorced women and those living in urban areas were identified as high risk groups. PMID- 2101671 TI - Burkitt's lymphoma: a pericardial presentation. AB - Described herein is a case of childhood Burkitt's lymphoma initially presenting as a pericardial effusion. A cytological diagnosis was made from a Wright's Giemsa stained cytospin preparation. Supporting diagnostic evidence was provided by immunological surface marker analysis and electron microscopy. To our knowledge, Burkitt's lymphoma has not hitherto been diagnosed initially from the morphology of cells in pericardial fluid. PMID- 2101672 TI - Clinical approach to fine needle biopsy: a note of caution. PMID- 2101673 TI - Cervical cytology in the European community. PMID- 2101674 TI - The effect of tamoxifen on cervical squamous maturation in Papanicolaou stained cervical smears of post-menopausal women. AB - Using cervical smears obtained as part of routine gynaecological examinations, a retrospective study of the effects of the drug tamoxifen on squamous epithelial maturation of the cervix of post-menopausal women being treated for advanced breast cancer was made. The degree of squamous epithelial maturation was quantitated by using the Maturation Index and the Maturation Value. Although tamoxifen is a synthetic, non-steroidal compound classified as anti-oestrogenic, the findings indicate that this drug commonly produces a level of squamous maturation indicative of oestrogenic stimulation in Papanicolaou stained cervical smears from post-menopausal patients receiving this drug. Knowledge of the oestrogenic effect of tamoxifen in the cervix can obviate clinical concern about endometrial carcinoma. PMID- 2101675 TI - Cytological grading of breast carcinoma--a feasible proposition? AB - Fine needle aspiration cytology (FNAC) of the breast is widely used in the diagnosis of breast carcinoma. In some centres this is sometimes the only diagnostic procedure performed prior to definitive treatment. A grading system based on cytology would be helpful in the selection of patients for appropriate therapy. The aim of this study, therefore, was to devise such a system for grading breast carcinoma based on cytological features alone. The features assessed were the degree of cell clustering, nuclear pleomorphism, nuclear diameter, the presence of multiple, easily visible nucleoli and necrosis. Cytological features were compared to the histological grade of the tumours following excision. Discriminant analysis showed that the features with the closest correlation with histological grade were nuclear diameter, nuclear pleomorphism and the presence of nucleoli. A scoring system based on these three parameters enabled the classification of tumours into high and low cytological grades which showed a close correlation with histological grade. PMID- 2101676 TI - Fine needle aspiration cytodiagnosis of anaplastic carcinoma and malignant haemangioendothelioma of the thyroid in an endemic goitre area. AB - Between 1970 and 1987, 20,028 fine needle aspirates (FNA) of the thyroid have been examined in the Department of Pathology of the University of Innsbruck, Austria. During this period 92 cases of anaplastic carcinoma and 16 cases of malignant haemangioendothelioma (MHE) of the thyroid were diagnosed. Forty-three out of these 108 highly malignant tumours of the thyroid underwent FNA pre operatively (39.1%). Thirty-seven FNA contained numerous cells of a highly malignant tumour. Five specimens (11.8%) contained only necrotic material and inflammatory cells. In one case of an anaplastic carcinoma no malignant cells could be demonstrated in FNA. We conclude that pre-operative FNA of highly malignant thyroid tumours may contribute substantially to subsequent clinical management. PMID- 2101678 TI - Fine needle aspiration. PMID- 2101677 TI - A microglandular adenosis-like lesion simulating tubular adenocarcinoma of the breast. A case report with cytological and histological appearances. AB - Although rare, microglandular adenosis of the breast is well recognized as a benign lesion which mimics tubular adenocarcinoma. In this paper we present a case of a complex microglandular adenosis-like lesion which was thought to be suggestive of tubular adenocarcinoma by fine needle aspiration cytology. The problem of the cytological distinction of microglandular adenosis from tubular adenocarcinoma is discussed. PMID- 2101679 TI - Carcinoma in situ of the cervix and its malignant potential. A lesson from New Zealand. AB - An overview of studies attempting to define the natural history of carcinoma in situ of the cervix suggests that 20-30% of lesions progress to invasive carcinoma within 5-10 years. This risk of invasion and the inability to predict when invasion might occur has been reinforced by a judicial enquiry in New Zealand so that protocols that include withholding treatment are no longer justifiable. Once a diagnosis of cervical carcinoma in situ is established appropriate treatment is mandatory. PMID- 2101680 TI - Demonstration of oestrogen receptor in symptomatic breast carcinoma, using fine needle aspiration cytology. AB - Oestrogen receptor immunocytochemical assay (ER-ICA) was used to determine oestrogen receptor (ER) content of cells in fine needle aspirate (FNA) specimens from 88 breast carcinomas. In 49 of these the radioligand binding assay for oestradiol was available for comparison. The predictive value of ER-ICA staining for a positive radioligand binding assay (greater than 10 fmol/mg protein) was 95%. Although the predictive value of negative staining was only 66%, 34 out of 37 ER-ICA negative tumours had radioligand binding assays below 60 fmol/mg protein. ER-ICA staining showed a strong positive correlation with age of the patient, positivity being rare before the menopause. There was a weak inverse correlation with tumour grade but none with tumour size or lymph node status. The assessment of ER by immunocytochemistry using FNA cytology is a rapid technique, which may easily be repeated and provides a pre-operative assessment of ER status. It allows confirmation that tumour cells are present in the sample and an assessment of tumour heterogeneity. PMID- 2101681 TI - Morphometric analysis of fine needle aspirates from breast lesions. AB - In an attempt to discover the morphometric variables with the most diagnostic power in the differentiation of benign from malignant breast disease, 20 unequivocally benign and 20 unequivocally malignant and histologically confirmed breast aspirates were examined on an image analyser. It was found that standard deviation of nuclear area was the most discriminant variable. Then 23 aspirates initially diagnosed as 'suspicious of malignancy' were measured by the same technique, and standard deviation of nuclear area correctly differentiated all but three cases. PMID- 2101682 TI - Fine needle aspiration cytology in a case of florid gynaecomastia. AB - A case of gynaecomastia examined by fine needle aspiration cytology is reported. The pitfalls in trying to obtain a cytological diagnosis in the florid proliferative stage of the disease are detailed together with an account of the natural history. PMID- 2101683 TI - Pseudoepithelial pattern in smears prepared from fine needle aspirates of plasmacytomas. AB - A pseudoepithelial pattern was observed in smears prepared from fine needle aspirates (FNA) from three plasmacytomas. In one case cells displayed a markedly granular, 'oncocytic' cytoplasm. Granularity of the cytoplasm was due to a large number of mitochondria as shown by electron microscopy. B-lymphocytic origin of the neoplasms was confirmed by immunocytochemistry. PMID- 2101684 TI - Overlapping morphology in thyroiditis (Hashimoto's and subacute) and Grave's disease. PMID- 2101685 TI - T-DNA presence and opine production in tumors of Picea abies (L.) Karst induced by Agrobacterium tumefaciens A281. AB - The hypervirulent Agrobacterium tumefaciens strain A281 formed frequent tumors (31%) on Picea abies (Norway spruce), an economically important tree species in Swedish forests. Three-month-old seedlings were inoculated and tumors were established that grew hormone-independently in culture. Tumors contained agropine and mannopine/mannopinic acid as determined by acid pH paper electrophoresis. In addition, DNA hybridization studies showed that the DNA from these tumor lines contained sequences homologous to Ti plasmid T-DNA, whereas wild-type spruce seedling DNA did not. These results suggest that Agrobacterium vectors can be used for gene transfer into this important forest species. PMID- 2101686 TI - Tobacco genes encoding acidic and basic isoforms of pathogenesis-related proteins display different expression patterns. AB - The induction by cytokinin stress and ethylene of nine different tobacco mosaic virus-inducible mRNA classes (termed A-I) encoding pathogenesis-related (PR) proteins was studied. The induced mRNA levels were compared to basal levels in healthy tobacco plants grown in tissue culture and in a greenhouse. Cytokinin stress and ethylene were found to induce different subsets of the mRNAs, indicating that ethylene is not the primary inducing signal in cytokinin-stressed shoots. mRNAs F, H and G encoding the basic hydrolytic enzymes chitinase, beta 1,3-glucanase and a basic equivalent of PR-1, respectively, were found to be expressed at high levels in roots of healthy plants. mRNAs D, I and B encoding the acidic equivalents of the proteins proved to be present at low levels in healthy plants. These results indicate that genes encoding basic and acidic isoforms of pathogenesis-related proteins are differentially regulated. PMID- 2101687 TI - Molecular cloning and sequencing of a cDNA for an auxin-repressed mRNA: correlation between fruit growth and repression of the auxin-regulated gene. AB - A complementary DNA (cDNA) library has been constructed in lambda gt 10 from poly(A)+ mRNA isolated from auxin-deprived strawberry receptacles. By differential plaque filter hybridization, a cDNA (lambda SAR5) to an auxin repressed mRNA has been isolated. The expression of the auxin-repressed gene is studied at various stages of normal fruit development and in fruits of variant strawberry genotype using lambda SAR5 as a probe. Northern analyses of RNA isolated from pollinated and unpollinated fruits of various developmental stages revealed that mRNA corresponding to the lambda SAR5 clone is repressed during normal fruit development, and the level of lambda SAR5 mRNA is regulated by endogenous auxin. Furthermore, results with both normal and variant genotype strawberry fruit indicate that there is a positive correlation between growth of strawberry fruit and repression of mRNA corresponding to the lambda SAR5 clone. The lambda SAR5 cDNA has been sequenced and is 723 nucleotides in length. The deduced protein has 111 amino acid residues with a molecular mass of 12.5 kDa. The putative polypeptide starts at nucleotide position 20 and ends at 352. The molecular weight of the predicted polypeptide is in agreement with the molecular weight of the in vitro translated polypeptide of hybrid selected mRNA. A comparison of the nucleotide and deduced amino acid sequence of lambda SAR5 with nucleotide and protein sequences in data banks has not revealed any homology to known proteins. PMID- 2101688 TI - Nucleotide sequence of Citrus limon 26S rRNA gene and secondary structure model of its RNA. AB - The complete nucleotide sequence of Citrus limon 26S rDNA has been determined. The sequence has been aligned with large ribosomal RNA (L-rRNA) sequences of Escherichia coli, Saccharomyces cerevisiae and Oryza sativa. Nine extensive expansion segments in dicot 26S rRNA relative to E. coli 23S rRNA have been identified and compared with analogous segments of monocot, yeast, amphibian and human L-rRNAs. A secondary structure model for lemon 26S rRNA has been derived based on the refined model of E. coli 23S rRNA. It has been compared with other eukaryotic L-rRNAs models in terms of location of functionally important regions. Origin and evolution of L-rRNA expansion segments are discussed. PMID- 2101689 TI - Structural characterization of a rice actin gene. AB - We have isolated and sequenced a full-length cDNA clone containing information for the rice actin gene RAc1. Transcript terminus mapping and sequence alignment between the RAc1 cDNA clone and a previously isolated RAc1 genomic clone were used to determine the structure of the RAc1 gene. This allowed us to make the first complete structural characterization of a plant actin gene. The analysis revealed the presence of a 5'-noncoding exon, separated by an intron, from the first translated exon of the RAc1 gene. This is one of the few reported cases of a plant gene containing such a 5'-noncoding exon. Sequence comparison between the previously isolated plant actin genes suggests that such an exon may be a common feature of plant actin gene structure. The present study also confirms that the rice actin gene family is composed of at least eight unique members. PMID- 2101690 TI - Functional analysis of a complex oncogene arrangement in biotype III Agrobacterium tumefaciens strains. AB - The ubiquitous grapevine-associated octopine/cucumopine Ti plasmids of biotype III Agrobacterium tumefaciens strains carry two T regions, TA and TB, with a complex oncogene arrangement. Within the octopine/cucumopine group, two main strain types were identified: 'large TA' strains with a TA region resembling the TL region of the biotype I octopine strain Ach5 and 'small TA' strains with a similar T region organization as the 'large TA' strains but with a large internal TA deletion. Structural and functional studies of the representative 'large TA' strain Tm4 revealed six oncogenes. Each oncogene was inserted in a disarmed vector and tested for biological activity using the corresponding oncogenes of Ach5 as standards. Five Tm4 oncogenes, TA-iaaM, T-ipt, T-6b, TB-iaaH and TB-iaaM, were shown to be active, the IS-interrupted TA-iaaH gene was inactive. To study the role of each gene in the pTiTm4 context, several single and multiple pTiTm4 mutations were constructed. It was shown that whereas TA-iaaM and TB-iaaH are essential for tumour formation on grapevine, T-ipt, T-6b and TB-iaaM are not. The avirulence of the TA-iaaM- mutant was shown to be due to an inhibitory effect of the T-ipt gene, since a TA-iaaM-/T-ipt- double mutant was fully virulent. We conclude that the TA-iaaM gene of 'large TA' strains is specifically required to counteract the tumour growth inhibiting activity of the T-ipt gene. Both TA-iaaM and T-ipt are absent from the 'small TA' strains. A model on the roles and interactions of the different oncogenes in 'large TA' and 'small TA' strains is presented. PMID- 2101691 TI - Isolation and characterization of cDNAs from Lycopersicon esculentum and Arabidopsis thaliana encoding the 33 kDa protein of the photosystem II-associated oxygen-evolving complex. AB - We have identified and isolated cDNA clones of the 33 kDa protein of the oxygen evolving complex (OEE1) from Lycopersicon esculentum (tomato) and Arabidopsis thaliana and determined their nucleotide sequences. The cDNA clones and antibodies prepared against OEE1 were used as probes to examine the expression of the oee1 gene with respect to regulation by light, organ specificity, and ripening stage of tomato fruit. The steady-state mRNA level is regulated by light, being present in light-grown plants and absent in etiolated seedlings. The oee1 transcripts that accumulate during growth in the light were reduced to non detectable or low levels by a 3-day dark treatment. The oee1 gene also exhibits differential expression in various organs of the tomato plant. Steady-state mRNA level was highest in immature leaves and absent in roots while the protein was most abundant in mature leaves and absent in roots. During tomato fruit ripening oee1 mRNA decreases to a low level in the pericarp while the protein level decreases below detection. The expression of oee1 appears to be under the control of a complex mechanism regulating both the amount of RNA and its translation. PMID- 2101692 TI - Synthesis and accumulation of pea plastocyanin in transgenic tobacco plants. AB - The pea plastocyanin gene in a 3.5 kbp Eco RI fragment of pea nuclear DNA was introduced into tobacco by Agrobacterium-mediated transformation. Regenerated plants contained pea plastocyanin located within the chloroplast thylakoid membrane system. Analysis of seedlings from a self-pollinated transgenic plant containing a single copy of the pea plastocyanin gene indicated that seedlings homozygous for the pea gene contained almost twice as much pea plastocyanin as seedlings hemizygous for the pea gene. Homozygous seedlings contained approximately equal amounts of pea and tobacco plastocyanins. The amount of tobacco plastocyanin in leaves of transgenic plants was unaffected by the expression of the pea plastocyanin gene. The mRNA from the pea gene in tobacco was indistinguishable by northern blotting and S1 nuclease protection from the mRNA found in pea. In both pea and transgenic tobacco, expression of the pea plastocyanin gene was induced by light in leaves but was suppressed in roots. Pea plastocyanin free of contaminating tobacco plastocyanin was purified from transgenic tobacco plants and shown to be indistinguishable from natural pea plastocyanin by N-terminal protein sequencing and 1H NMR spectroscopy. PMID- 2101694 TI - Nucleotide sequence of the small subunit of ribulose-1,5-bisphosphate carboxylase from the conifer Larix laricina. PMID- 2101693 TI - Octopine and nopaline strains of Agrobacterium tumefaciens differ in virulence; molecular characterization of the virF locus. AB - Octopine and nopaline strains of Agrobacterium tumefaciens were found to differ in virulence on Nicotiana glauca. This difference is due to the absence of a functional virF locus, which is necessary for efficient tumorigenesis on N. glauca, from the nopaline Ti plasmids. Genetic studies and DNA sequence analysis of the virF locus revealed that virF embraces one open reading frame coding for a hydrophilic protein with a molecular mass of 22,437 Da. Transcription of virF is directed from left to right, towards the T region, and is strongly induced by the phenolic compound acetosyringone. We established that virA and virG, two genes known to be essential for induction of the vir regulon, are necessary for acetosyringone-induced virF expression, implying that virF is a member of this vir regulon. Agrobacterium virF mutants can be complemented for tumor induction by co-infection with avirulent Agrobacterium 'helper' strains. We found that such 'helper' strains must express not only the virF gene but also the vir operons virA, virB, virD and virG. PMID- 2101695 TI - Nucleotide sequence of a gene encoding soybean repetitive proline-rich protein 3. PMID- 2101696 TI - Implant overview. PMID- 2101697 TI - Surface disinfectants: an overview for dental hygienists. PMID- 2101698 TI - Risk management practices for the dental hygienist. PMID- 2101699 TI - Clinical and laboratory tests to enhance periodontal diagnosis. 3. PMID- 2101700 TI - What's in a tube of toothpaste? PMID- 2101701 TI - AIDS education & training centers. PMID- 2101702 TI - Creating agreement: understanding the resistant patient. PMID- 2101703 TI - Target community need. PMID- 2101704 TI - The pregnant patient. PMID- 2101705 TI - Instrument sharpening--"the flat stone in motion". PMID- 2101706 TI - The ADA seal: what does it mean? PMID- 2101707 TI - Candida albicans: local and systemic infections. The hygienist's role. PMID- 2101708 TI - Dental needs: the well elderly. PMID- 2101709 TI - Root caries: the problem and the protocol. First of two parts. PMID- 2101711 TI - Mouth care: more than method. PMID- 2101710 TI - Adult orthodontics. PMID- 2101712 TI - Intra-oral photography. PMID- 2101713 TI - Desquamative gingivitis: a current perspective. PMID- 2101714 TI - Zoo animal dentistry: another breed of patient. PMID- 2101715 TI - Hepatitis B vaccine update. PMID- 2101716 TI - Dry socket: when normal healing is interrupted. PMID- 2101717 TI - Root caries: the problem and the protocol. Second of two parts. PMID- 2101718 TI - The needs of a cleft lip and cleft palate child. PMID- 2101719 TI - The contribution of inherited predisposition to cancer incidence. AB - Only a small proportion of cancers, arising in inherited syndromes such as polyposis coli, have an unequivocally inherited basis. Nevertheless, most common cancers show familial clustering, much of which may be due to inherited predisposition. If so, there may be wide variation in genetic susceptibility to common cancers. The precise models of susceptibility are unclear, but for ovarian cancer and breast cancer there is some evidence that a small proportion of cases result from highly penetrant dominant genes. This has been confirmed recently for breast cancer by genetic linkage studies. Clear evidence for genetic susceptibility has been obtained for Hodgkin's disease and nasopharyngeal carcinoma, where the existence of susceptibility genes at the HLA locus has been demonstrated by linkage analysis. These genes could account for the majority of cases of these cancers. Identification of other cancer susceptibility genes should be possible, either directly using linkage analysis, or through identification of constitutional phenotypes related to cancer risk. PMID- 2101720 TI - Genetic analysis of cancer in families. AB - Cancer is genetic, in the sense that it is caused by DNA alterations at the cellular level. On the other hand, the most important risk factors for the common cancers are environmental: cigarette smoking, environmental pollution, occupational exposures, poor diet, and so on. These two observations are not in conflict: the DNA alterations that lead to cancer are very likely to be caused by environmental mutagens. It would be valuable to know exactly what genes are altered to cause a specific cancer, because the effects of these alterations might then be reversible before cancer has a chance to develop. A key to identifying these cancer genes may lie with rare families at extremely high risk of a specific cancer. Unlike most cancer patients, members of these families may inherit an alteration that confers increased susceptibility to cancer. In these rare instances, cancer is a genetic disease at the level of the family, as well as at the level of the cell. Therefore, in these families, genes predisposing to cancer can be mapped in the same way as genes for purely genetic diseases like sickle cell anaemia, cystic fibrosis, and Huntington's disease. The hypothesis that underlies the mapping of cancer genes in families is that the genes inherited in altered form in these rare families are the same genes that are altered in somatic cells of individuals without a remarkable family history of cancer. This hypothesis has proved correct for retinoblastoma. Genes responsible for other rare cancers have been mapped in families as well: neurofibromatosis, multiple endocrine neoplasia, Wilms' tumour, and colon cancer following familial adenomatous polyps, among others. Genes responsible for common cancers are also being defined by genetic analysis, most notably breast cancer and colon cancer. This review summarizes why, how, and what genetic analysis of families can reveal about human cancers. PMID- 2101721 TI - Metabolic factors in cancer susceptibility. AB - The majority of cancers appear to arise from gene mutations induced by chemicals in the environment. Although the resulting metabolic changes which confer the tumour phenotype are still poorly defined, considerable progress has been made in identifying the genes responsible. In addition, there have been significant advances in identifying the genes important in determining the sensitivity of cells to tumorigenic agents. Animal studies clearly demonstrate that individual differences in their expression can lead to profound differences in cancer susceptibility. There is a growing body of evidence that polymorphisms in certain of these genes are also involved in cancer susceptibility in man. This article describes the identification and role of specific metabolic pathways in the tumour initiation and how polymorphisms in their function could relate to cancer susceptibility. PMID- 2101722 TI - Genomic imprinting and cancer. AB - Genomic imprinting results in a functional non-equivalence of parental chromosomes, presumably by epigenetic modification of the genome, and is required for normal mammalian development. In general, reciprocal phenotypes are observed in embryos containing alterations in the dosage of parental chromosomes, for example where both copies of chromosomes or chromosomal regions are derived from one parent. These phenotypes indicate that duplications of maternal chromosomes inhibit embryonic growth and proliferation whereas duplications of the paternal genome result in enhanced cell growth and proliferation. Alterations in the dosage of parental chromosomes have recently been observed in some forms of recessive tumour in man. Here we discuss the role and possible mechanisms of genomic imprinting during embryogenesis and attempt to draw parallels between the parental origin of the loss of heterozygosity observed in some human tumours and the developmental phenotypes that arise in mice with similar distortions of parental origin. These observations strongly implicate genomic imprinting in the genesis of some forms of tumour and, more generally, in the genetic predisposition to cancer. PMID- 2101723 TI - The fruit fly Drosophila and the fish Xiphophorus as model systems for cancer studies. AB - Genetic and molecular analyses of Drosophila have shown that tumorigenesis may arise from inactivation of single genes controlling cell growth and differentiation. Recessive mutations in a series of genes interrupt the differentiation of primordial cells and result in overgrowth, producing either hyperplasia or neoplasia. In mutant animals tumours form in either the optic centres of the larval brain, the imaginal discs or the haemopoietic organs. In Drosophila 17 genetic loci giving rise to neoplasia and six loci producing hyperplasia have been identified. The lethal(2)giant larvae gene constitutes the prototype of these genes. Its molecular cloning and analysis have demonstrated that the tumor phenotype results from a lack of gene function. Furthermore, tumour prevention was achieved by introducing a normal copy of l(2)gl into the genome of l(2)gl- deficient animals, showing that the l(2)gl gene behaves as a tumour suppressor or anti-oncogene. Melanomas of genetic origin develop in interspecies hybrids of the fish Xiphophorus. The melanoma appears when a sex linked chromosomal gene (Tu) is present among the progeny animals lacking an autosomal locus Differentiation, which acts as a tumour suppressor gene. A sequence homologous to the erb-B gene can be associated to the sex chromosomal Tu locus. This gene encodes a receptor tyrosine kinase related to the EGF-receptor, and its activation and overexpression are thought to play a critical part in melanoma formation. PMID- 2101724 TI - The molecular genetics of retinoblastoma. AB - Retinoblastoma is a potentially hereditary cancer. Refinement of the genetic and epidemiological analysis of the disease has uncovered two distinct classes of retinoblastoma. Sporadic retinoblastoma is generally unilateral and unifocal, and is diagnosed at the late age of about two years. A few of these sporadic cases are probably due to a germ cell mutation inherited from a parent and hence can be classified as hereditary. Familial retinoblastoma is generally diagnosed at an earlier age, at 11 months, and is typically bilateral and/or multifocal. These observations have been incorporated into a 'two hit' mutational inactivation hypothesis of the origin of retinoblastoma. The molecular cloning and characterization of a candidate retinoblastoma susceptibility gene and its gene product has allowed a critical testing of this hypothesis. All of the predications of the model have been confirmed by experiment. These include inheritance of one mutated retinoblastoma susceptibility (RB) allele as the origin of hereditary retinoblastoma, subsequent loss of the remaining allele upon the genesis of the tumour, the involvement of the same RB gene in both sporadic and hereditary retinoblastoma, the somatic mutation of both RB alleles in sporadic retinoblastoma, the lack of evidence for expression of a normal RB gene product in any retinoblastoma yet examined, the inactivational nature of RB mutations and the recessiveness of these mutated alleles. The RB gene also exhibits suppression of neoplastic properties when introduced into retinoblastoma cells and also into some other tumour cells. These results mutually reinforce the two hit inactivation hypothesis as well as the cloned gene's correct identification as the retinoblastoma susceptibility locus. The confirmation of this hypothesis is, therefore, nearing completion. The definitive proof is achievable with the advent of chimeric mouse technology, which will allow construction of mice with one or both RB alleles that have been inactivated by mutation. Analysis of such mice may allow us to determine if inactivation of both RB alleles is necessary and sufficient for the development of retinoblastoma and possibly other tumour types. The molecular isolation of the RB gene is an important achievement in research on cancer. For the first time, it has become possible to examine, at the molecular level, genes which suppress the tumorigenicity of cancer cells. Analysis of such cloned genes should yield insight into mechanisms of oncogenesis, gene regulation and cellular differentiation complementary to the knowledge which has long been accumulating from the study of oncogenes. PMID- 2101725 TI - The genetics of colorectal cancer. AB - Two features of colorectal cancer have greatly aided the recent progress in understanding its genetics: firstly the majority of colorectal cancers arise from premalignant adenomatous polyps allowing the analysis of somatic genetic changes during tumorigenesis, and secondly there are several well defined inherited syndromes that predispose to colorectal cancer in an autosomal dominant manner. The familial polyposis gene has been mapped to chromosome 5q and loss of material on chromosome 5 shown in a large proportion of sporadic (non-familial) adenomas and carcinomas. Allele loss has also been found in a high proportion of colorectal cancers on chromosomes 17 and 18 and the respective genes involved identified as that coding for the oncoprotein p53 on 17p and the DCC ('deleted in colorectal carcinomas') gene on 18q. In addition activation of k-ras is found frequently in colorectal adenomas and carcinomas. The development of colorectal neoplasia is associated with the accumulation of genetic changes. Family studies of apparently sporadic colorectal cancer probands have shown an increased incidence of adenomas and carcinomas in first degree relatives. More recently pedigree studies have suggested that an inherited predisposition may be responsible for the majority of colorectal tumours. PMID- 2101726 TI - Genetics of human breast cancer. AB - During the past five years, important progress has been made in the identification of genes and/or chromosomal rearrangements that may have direct relevance for the development of human breast cancer. Along with rapid advances in the field of human genome characterization, the number of molecular tools to examine the genomic changes occurring in breast cancer cells is expanding rapidly. Therefore, the major challenge is not so much the identification of tumour specific genome alterations, but rather the interpretation of the findings in terms of biological implications. Since clearly defined precursor lesions are lacking in breast cancer, a multidisciplinary approach will be necessary to arrive at a more complete understanding of the established genetic alterations. PMID- 2101727 TI - Genetics of melanoma. AB - The goal of genetic analysis of malignant melanoma is to identify genes involved in the transformation of melanocytes and melanoma tumour progression. Three basic approaches have been used to analyze tumour progression in melanoma, and these include: (1) performing genetic linkage analysis on familial melanoma to identify the chromosomal location of genes which predispose individuals to melanoma; (2) examining tumours cytogenetically to identify frequently rearranged regions of the genome which presumably mark the location of genes involved in the evolution of melanoma; and (3) screening melanomas, using molecular techniques, to identify mutated oncogenes or tumour suppressor genes that play crucial roles in melanoma development. These studies provide strong evidence that genes on chromosomes 1, 6, 7 and 9 are involved in the aetiology of human melanoma. PMID- 2101728 TI - Neuroblastoma: clinical significance of genetic abnormalities. AB - Two genetic events have been identified so far which are characteristic of neuroblastomas. These include loss of a critical region on the distal short arm of chromosome 1 and amplification of the MYCN proto-oncogene. Our studies suggest that the two genetic events may be related and that loss of heterozygosity (LOH) for chromosome 1p may precede the development of amplification. When these features are combined with flow cytometric analysis of DNA content, three distinct genetic subsets of neuroblastomas can be identified. The first is characterized by a hyperdiploid or near-triploid modal karyotype, with few if any cytogenetic rearrangements. These patients are generally less than one year of age with localized disease and a good prognosis. The second group is characterized by a near-diploid or near-tetraploid karyotype, with no consistent rearrangement identified so far. They are generally older patients with more advance stages of disease that progress slowly and are frequently fatal. The third group is characterized by a near-diploid or tetraploid karyotype, with deletions or LOH for chromosome 1p, amplification of MYCN or both. These patients are generally older with advanced stages of disease which is rapidly progressive. Thus, genetic analysis of neuroblastoma cells provides information that has prognostic significance and can direct the choice of treatment more appropriately. PMID- 2101729 TI - Domoic acid toxicity. Introduction. PMID- 2101730 TI - Memory loss following domoic acid intoxication from ingestion of toxic mussels. PMID- 2101731 TI - PET studies of domoic acid poisoning in humans: excitotoxic destruction of brain glutamatergic pathways, revealed in measurements of glucose metabolism by positron emission tomography. AB - We used positron emission tomography to measure hippocampal and medial temporal lobe metabolism in brains of patients intoxicated by domoic acid from Prince Edward Island mussels. This analog of kainic acid specifically excites certain neurons in the hippocampus, and the study revealed a severe reduction of glucose metabolism in this part of the brain which paralleled the absence of long-, medium-, or short-term memory in these patients. PMID- 2101732 TI - Gastrointestinal effects of contaminated mussels and putative antidotes thereof. AB - A recent outbreak of amnesic shellfish poisoning (ASP) in Atlantic Canada was characterized by severe gastrointestinal and central nervous system pathology. We examined the gastrointestinal effects of an acidic extract of blue mussels contaminated with domoic acid, the suspected toxin responsible for the ASP. We also tested the gastric effects pure domoic acid as well as a putative antagonist of neuroexcitant amino acid receptors, kynurenic acid. Mussel extract produced gastric (antral) ulcers, duodenal ulcers, gastric and duodenal hyperemia and bleeding, as well as peritoneal ascites. Kynurenic acid protected significantly against extract-induced gastropathy, particularly when given 60 or 75 minutes after extract. Pure domoic acid resulted in fatalities in all infant mice tested. These animals exhibited gastric bleeding and hemorrhage, especially at the higher doses employed. In otherwise untreated rats, kynurenic acid exerted significant anti-stress ulcer and anti-gastric secretory effects, but was less effective at blocking ethanol-induced gastric lesions. We suggest that there may be both peripheral as well as central effects of kynurenic acid in modulating normal and pathological gastric function. PMID- 2101733 TI - Domoic acid toxicity. Panel discussion: treatment. PMID- 2101734 TI - Domoic acid toxicity. Panel discussion: short-term research priorities. PMID- 2101735 TI - The toxicology of domoic acid administered systemically to rodents and primates. PMID- 2101736 TI - Chemistry, biology, and toxicology of domoic acid and its isomers. AB - The causative agent of toxicity in cultured mussels from a localized area of eastern Prince Edward Island has been identified as domoic acid, a neuroexcitatory amino acid. The toxin was isolated by a number of different bioassay-directed separation techniques including high-performance liquid chromatography (HPLC), high-voltage paper electrophoresis (HVPE), and ion exchange chromatography, and characterized by a number of spectroscopic techniques including ultraviolet, infrared, mass spectrometry, and nuclear magnetic resonance. The isolation and purification methods are described in detail and some new analytical data for domoic acid are reported. A plankton bloom at the time of the outbreak gave positive mouse bioassays and consisted almost entirely of the pennate diatom, Nitzschia pungens f. multiseries. A positive correlation was found between the number of N. pungens cells and the concentration of domoic acid in the plankton. N. pungens f. multiseries isolated from Cardigan Bay produced domoic acid de novo during stationary phase culture at levels (1 to 10 pg/cell) comparable to values estimated for N. pungens in the plankton samples. We conclude that N. pungens was the major source of the domoic acid in toxic mussels in eastern Prince Edward Island. The recurrence, in November 1988, of a monospecific bloom of N. pungens and the presence of domoic acid in plankton and mussels reinforces this conclusion. PMID- 2101737 TI - Chronology of the toxic mussels outbreak. PMID- 2101739 TI - Panel discussion: evidence that domoic acid was the cause of the 1987 outbreak. PMID- 2101738 TI - Mussel culture and the accumulation of domoic acid. AB - The cultured mussel industry of Prince Edward Island had never experienced a toxic disease problem until November of 1987. With the successful use of the long line culture system, the yearly production of fresh mussels to the gourmet food market had risen to close to 3.2 million pounds (1.46 million kg) of product. The physiology of this sessile bivalve and its method of feeding and location in the estuary leave it prone to the accumulation of a widely distributed biotoxin. Eastern Prince Edward Island became the epicentre of domoic acid-intoxicated mussels as early as 10 November 1987 (retrospective samples) during an intense bloom of the diatom Nitzschia. Mussels were able to accumulate large amounts of the domoic acid with little effect on their own well-being. Despite being in low water temperatures (below 4 degrees C) and under thick ice cover, the levels of the toxin decreased and were undetectable in about 6 weeks. The following year the toxin was detected in much smaller amounts, and the levels of toxin accumulation demonstrated a variable lag time with the increase in concentration of Nitzschia available in the water column. The sales of Prince Edward Island cultured mussels have rebounded to about 140% of the pre-domoic acid crisis. PMID- 2101740 TI - Domoic acid toxicity. Panel discussion: definition of the syndrome. PMID- 2101741 TI - Acute manifestations of domoic acid poisoning: case presentations. PMID- 2101743 TI - The human neuropathology of encephalopathic mussel toxin poisoning. PMID- 2101742 TI - Amnesic shellfish poisoning: a new clinical syndrome due to domoic acid. PMID- 2101744 TI - Neuropathology of experimental domoic acid poisoning in non-human primates and rats. PMID- 2101745 TI - Neurological sequelae of domoic acid intoxication. PMID- 2101746 TI - Sensitive murine model and putative antidotes for behaviorial toxicosis from contaminated mussel extracts. AB - The recent outbreak of "amnesic" mussel poisoning syndrome, attributed to domoic acid contamination of edible mussels claimed several lives and left many victims impaired with a peculiar loss of memory. We administered the whole mussel extract (WMX) and the mussel hepatopancreas extract (MHX, hepatopancreas being the major site for sequestration of domoic acid in mussels) in Swiss-Webster mice. A characteristic syndrome featuring sluggishness, scratching stereotypy, convulsions and death was noticed. Infant mice were some 3- to 4-fold more sensitive to the WMX toxicity. Kynurenic acid (KYN), an endogenous nonselective excitotoxin antagonist offered significant protection against the toxicosis after its onset had been provoked by the mussel extract. This observation emphasizes the feasibility of using KYN or related compounds in the therapy of poisoning from excitotoxins. As a logical extension of this possibility we examined the possibility that endogenous KYN could be exploited for similar protection against domoate toxicosis in our murine model. The time frame during which KYN was protective was increased by probenecid, a blocker of organic acid transport and by tryptophan, a precursor of endogenous KYN. We examined also the classical anticonvulsants phenytoin and ethosuximide, as well as dextromethorphan at its excitotoxin antagonistic dose. The infant mouse model of domoate-toxicity holds promise for being developed into a rapid, sensitive, reliable and inexpensive biological assay for screening commercial batches of mussel for excitotoxin contamination. Kynurenic acid and dextromethorphan should be further examined as antidotes for possible therapeutic use in existing victims and in the treatment of future domoate toxicosis occurring here or elsewhere. PMID- 2101747 TI - [Evaluation of nutritional status using blood parameters in bottle-fed infants after the introduction of a new system of feeding]. AB - The author presents the results of several years' efforts of paediatricians to prolong breastfeeding. He compares a group of 1970 mothers in 1974 with a group of 1550 mothers in 1986-1987. After introduction of the innovated infant feeding system (1968) they collected blood samples from 703 normal artificially fed infants aged 3-12 months fed during the second trimester dried undiluted "Sunar" milk, enriched with 4 mg Fe/100 g. In addition to the basic group they had a comparable group of infants fed during the 4th-6th month Sunar in 2/3 dilution. In the investigated groups they examined the haemoglobin (Hb) level, the number of erythrocytes (Er), haematocrit (Ht) serum iron (SFe) and total binding capacity (CVK). By calculation they assessed the mean haemoglobin concentration of red blood cells (SFK), the mean haemoglobin level (HbEr), the mean red cell volume (SOEr) and the iron saturation of transferrin (ST). In the basic group, as compared with 1982-83, the frequency of sideropenic anaemia of artificially fed infants declined. At the age of 4-6 months the authors found 15% anaemic infants, as compared with 29% in the group fed 2/3 Sunar. According to the author the incidence of sideropenic anaemia in the basic group declined during the second trimester due to the higher iron intake. PMID- 2101748 TI - [Hyperimmunoglobulinemia in children with chronic Epstein-Barr virus infection]. PMID- 2101749 TI - [Clinical diagnosis and laboratory study of acute respiratory diseases of viral origin in children]. AB - The authors analyzed retrospectively a group of 477 children aged two months to 16 years (mean age 6 years and 5 months), hospitalized on account of acute respiratory disease and subjected to virological examination. The aetiology was revealed in 53% of the sick children. In the elucidation of the aetiology participated a number of respiratory viruses, in particular the respiratory syncytial virus. The clinical picture of the disease was very varied. It was confirmed that the clinical picture does not make it possible to express in a considerable proportion of patients suspicion of an actual infectious aetiology. A mixed aetiology of acute respiratory diseases and a varied clinical picture indicate the necessity of a rapid virological and bacteriological examination in hospital practice. PMID- 2101750 TI - [Surgical treatment in primary tumors of the liver in children (in a group of 37 children)]. AB - The authors present an account of 37 children with primary hepatic tumours at the age of 1 to 16 years. The mortality in the group was 50%. Right-sided lobectomy on account of a hepatoblastoma was performed in 13 children, probatory excision on account of an advanced process in 9, left-sided lobectomy only in five children. The most frequent tumour was a hepatoblastoma in infants, followed by haemangioma and a hepatocellular carcinoma. The authors draw attention to the importance of careful examination of the abdomen by palpation as the first possible diagnostic guide. They emphasize the importance of sonography and arteriography of the hepatic vein in the preoperative examinations. PMID- 2101751 TI - [Intra-abdominal complications of ventriculoperitoneal shunt in the treatment of hydrocephalus in children]. PMID- 2101752 TI - [Use of green light in the treatment of neonatal hyperbilirubinemia]. PMID- 2101754 TI - [Nonsteroidal antirheumatic agents in pediatric practice]. PMID- 2101753 TI - [Cytogenetic examination of amniotic fluid specimens in the 2d trimester of pregnancy (personal experience 1981-1989)]. AB - The authors analyze a group of pregnant women examined at the Chair of Biology and Parasitology of the Medical Faculty J. A. Komensky's University between 1981 and the end of August 1989. During this period they cultivated cells from 1755 specimens of amniotic fluid. In the article they evaluate the detection rate of pathological conditions during this period. PMID- 2101755 TI - [Children with recurrent abdominal pain and their prognosis]. PMID- 2101756 TI - [Bone age of preschool-age children in the Eastern Slovakia Region]. AB - In a group of 579 children the bone age was assessed by the Tanner-White house II method. It was revealed that girls up to the age of three years have lower values of bone age than boys who are ahead in subsequent age groups. Boys lagged behind as regards bone age in relation to chronological age by 0.4 years and girls by 0.3 years. PMID- 2101757 TI - [Accumulation of patients with Potter's sequence]. PMID- 2101758 TI - [Button batteries as foreign bodies in the digestive tract of children]. PMID- 2101759 TI - [Children as a population group at risk for toxoplasma infection]. PMID- 2101760 TI - [Which disinfectant should be used in incubators?]. PMID- 2101761 TI - [New recommendations for nutritional requirements of infants, children and adolescents in Czechoslovakia]. PMID- 2101762 TI - Predictable veneer colors: a checklist for success. Decisions at four critical junctures govern your outcomes. PMID- 2101763 TI - After 50 years, acrylic resins still productive. New technology has overcome many of the objections practitioners once advanced. PMID- 2101764 TI - Halting the long-term progress of perio ills. A synopsis of the essentials of treatment and care. PMID- 2101765 TI - Children's hygiene. Family relationships hold the key to motivation. PMID- 2101766 TI - Florida preceptorship plan awaits first-round ruling. Hygienists oppose alternative training. PMID- 2101767 TI - Light-curing renaissance makes materials popular. Technological upgrades boost quality in light-curing devices. PMID- 2101768 TI - Gayso bridge offers upgrade in capability for retention. PMID- 2101769 TI - Glass ionomers increase practitioner efficiency. Techniques with today's generation can be tooth-saving and time saving. PMID- 2101770 TI - Ionomers far from extinct as useful dental material. Some limitations persist, but new applications are developing. PMID- 2101771 TI - Class IV technique overcomes snags in frailty, esthetics. New method conserves patients' teeth--and cash. PMID- 2101772 TI - Profiting from practice. PMID- 2101774 TI - Microfills retain importance. Hybrids not optimal for every restoration. PMID- 2101773 TI - Prefabricated post technique examined. PMID- 2101775 TI - 'Giant steps forward' operative procedures evolving. PMID- 2101776 TI - Subgingival brushing. Tested techniques resist bacterial growth, reduce bleeding and lessen inflammation. PMID- 2101777 TI - Potential of bifonazole for direct lethal action. AB - Time-kill type experiments were designed to assess the potential of bifonazole, a topical antifungal imidazole-containing drug, for its capacity to exert growth phase-dependent direct physicochemical lethal action against opportunistic yeast pathogens. Test organisms included two strains of Candida albicans and one of Candida parapsilosis. In contrast to the reference imidazole miconazole, which rapidly killed yeast cells in late lag to early logarithmic phase at concentrations between 10(-5) and 10(-4) M, bifonazole was inhibitory but not lethal. Bifonazole appears to lack a significant capacity for growth phase dependent direct lethal action against Candida species. PMID- 2101778 TI - CTX and its desacetyl derivative (des-CTX): interaction with some representative beta-lactamases and their related pattern of resistance to newer selected clinical isolates. AB - In this study the kinetic features of cefotaxime (CTX) and desacetyl-cefotaxime towards several representative beta-lactamases were investigated. Desacetyl-CTX was more stable to hydrolysis in comparison with cefotaxime for all the investigated enzymes. However, a cephalosporinase produced in Acinetobacter was progressively inactivated by both CTX and des-CTX. After prolonged incubation, dialysis partially restored the enzyme activity. Finally, both compounds were tested against selected resistant strains. It is concluded that des-CTX, because of either poor hydrolysis or prolonged half-life in body fluids, could contribute in vivo to the good antimicrobial properties of cefotaxime. PMID- 2101779 TI - In vitro antibacterial activity of cefotaxime and desacetylcefotaxime, alone or in combination, against gram-positive cocci. AB - The in vitro activity of cefotaxime and desacetylcefotaxime against Staphylococcus aureus, Staph. epidermidis and Streptococcus pyogenes was investigated. Synergy studies were performed using time-kill curves and the chequerboard test. The time-kill curves were performed on five strains each of Staph. aureus, Staph. epidermidis and Strep. pyogenes; cefotaxime and desacetylcefotaxime were tested alone or in combination at MIC and sub-MIC values. The chequerboard test was performed in microtitre plates on ten strains each of Staph. aureus, Staph. epidermidis and Strep. pyogenes: the results were interpreted by the fractional inhibitory concentration index. In some cases both methods showed synergistic interaction against the staphylococci tested. Indifference was observed against Strep. pyogenes. PMID- 2101780 TI - Pharmacokinetic study of neostigmine after intranasal and intravenous administration in the guinea pig. AB - It is well known that the nasal route may be an effective alternative to the administration of drugs poorly absorbed via oral administration. Thus an investigation of neostigmine bioavailability after nasal administration was undertaken. The neostigmine kinetic profiles after nasal and intravenous administration in the guinea pig have been compared, and results indicate good nasal absorption of neostigmine. At the same dose, no significant differences have been noticed between the two administration routes, as the area under the curve and the bioavailability index is close to 100%. Moreover nasal administration shows a longer plasmatic elimination compared with the i.v. route (t1/2 beta e.n. = 160.04 min; t1/2 beta i.v. = 23.35 min). Nasal absorption is observed to be dose-related. The present results suggest that nasal administration of neostigmine may be an effective clinical means in Myasthenia gravis therapy. PMID- 2101781 TI - Efficacy of captopril before thrombolysis in acute myocardial infarction: preliminary findings. AB - Studies on experimental animals indicate that ACE-inhibition might play an important role in coronary flow regulation and reperfusion damage limitation by alleviating non-irreversible myocardial damage and reducing Hyperkinetic Ventricular Arrhythmias (HVA) caused by reperfusion. This suggests the usefulness of captopril, an ACE-inhibitor containing the -SH group, in combination with systemic thrombolysis or mechanical revascularisation. The study was performed on seventy-two patients admitted to the hospital within 4 h of the onset of major cardiac symptoms due to Unstable Angina Pectoris (UAP) or Acute Myocardial Infarction (AMI). They were randomized either to treatment with oral captopril 15 min before thrombolysis (thirty-seven patients), or to thrombolysis followed by oral captopril on day 3-4 (thirty-five patients). In the early captopril-treated patients, a significant reduction in early arrhythmias was observed within 2 h, a lower incidence of late arrhythmias and a faster normalisation of necrosis enzymes. These data provide further evidence for the useful role of early captopril treatment in acute myocardial infarction. PMID- 2101782 TI - [Neuropsychological functioning in hebephrenic patients. Comparison between visual and auditory stimuli initially projected either in one or in both cerebral hemispheres]. AB - The performances of 14 hebephrenic patients and 14 normal subjects were studied through visual and auditory tests concerning the comparison of the number of stimuli projected either in the left, or in the right, or in both cerebral hemispheres. Schizophrenic patients were less efficient than normal subjects and, in both populations, no difference in the performances with regard to the locus of projection was observed. This suggests that information processing in schizophrenia might be deficient not only at the level of interhemispheric connections, but also in intrahemispheric functioning. PMID- 2101783 TI - [Tolerability of tianeptine in 170 patients with depression treated during one year]. AB - Tianeptine, a new antidepressant, has a tricyclic molecular structure. Its main biochemical activity consists of an increase in the reuptake of 5 HT both in men and animals, after acute and chronic administration. Tianeptine demonstrated its antidepressive clinical efficacy in several double-blind versus reference drug trials. A multicentre open trial, including depressed patients enabled us to evaluate the safety of tianeptine and to control the maintenance of the therapeutic efficacy in the course of its long-term prescription. Depressed patients included showed a major depressive episode, single (296.22) or recurrent (296.32) without melancholia or psychotic features, or a dysthymic disorder (300.40), according to DSM III criteria. A minimum MADRS score of a least 25, and the informed consent of the patients were required. The dose of tianeptine was 3 tablets per day (12.5 mg/tablet) with the possibility of increasing to 4 or decreasing to 2 tablets per day, depending on the symptomatology. Therapeutic efficacy was evaluated by item 1 and 2 of the Global Clinical Impression (CGI), the Montgomery and Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HARS) and the Hopkins Symptom Check-List (HSCL). Clinical and paraclinical safety were evaluated by CGI item 3, standardized ratings of patients' complaints (CHESS 84), interruption for side effects, evaluation of blood pressure, weight, biological parameters, EKGs. This intermediate evaluation concerns the first 170 depressed patients treated over a one-year period as well as the total group of patients included (n = 447).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101784 TI - [French translation and validation of Izard's differential emotion scale. Study of the verbal qualification of emotions]. AB - This work presents the validation of a French version of the emotional self rating scale by Izard (Differential Emotion Scale). This scale is based on the theory of the Discrete Emotions which proposes the existence of ten fundamental emotions. This self-rating scale consists of thirty emotional adjectives (three for each emotion). The validation was done by using a non inductive method (by asking the subject to describe his present emotional state) with 84 control subjects. It shows that this version is valid. Main results are first the binarisation of the emotions (positive and negative), then the existence of complex factors with psychopathological meaning after factorial analysis. These results are in agreement with a theory of expressive emotional levels more than with the theory of discrete emotions in psychopathology. PMID- 2101785 TI - [Detection of the anxio-depressive disorders in liaison psychiatry. Contribution of the General Health Questionnaire]. AB - Among self-report inventories of psychopathology for adults, the General Health Questionnaire (GHQ) is one of the prominent instruments developed for the screening of minor psychiatric morbidity. Four versions of the GHQ were provided from the original 60 items (GHQ-30, 28, 20, 12) and three different scorings have been suggested. A large number of validity studies, mostly favourable, have been performed and are reviewed in this paper. Recent work has suggested that the sensitivity of the GHQ to clinical change was fair, compared to the Present State Examination. The most recent version, the GHQ-28, was built from factor analyses of the 60-item version and covered four dimensions, with seven items each: anxiety and insomnia, severe depression, social impairment, somatic complaints, but their subscores were not independent. Several international extensive studies have confirmed that the GHQ was an interesting tool in Community as well as in General Practice. But, as it falls short from detecting all the chronic cases, research aimed at improving its quality in this direction is still in progress. The use of the French version of the GHQ-28 is expected to be encouraged. PMID- 2101786 TI - Partial purification of prolactin-like substance from snake (Ptyas mucosa) pituitaries. AB - Pituitary extract of the common rat snake (Ptyas mucosa) was found to be capable of displacing the binding of 125I-labelled ovine prolactin to female rat liver membranes, suggesting the presence of prolactin-like substance in snake pituitary. The snake prolactin-like substance was unadsorbed on Concanavalin A Sepharose, but adsorbed on DEAE-cellulose. The partially purified snake prolactin like substance was also capable of displacing the binding of 125I-labelled ovine prolactin to snake kidney and large intestine membranes. Chromatographic fractions derived from snake pituitary and which possessed potent growth hormone receptor binding activity were devoid of prolactin receptor binding activity, suggesting the existence of distinct prolactin-like and growth hormone-like substances in snake pituitary. PMID- 2101787 TI - Hyperglycemic effect of prolactin in anterior pituitary transplanted rats. AB - The role of prolactin as a diabetogenic hormone was based on studies describing the ability of administered prolactin to raise the level of serum glucose. In the present study, female rats were made hyperprolactinemic by the transplantation of two anterior pituitary glands under the renal capsule, obtained from littermate donors. Chronic hyperprolactinemia increased blood glucose and impaired the glycolytic pathway of hepatic carbohydrate metabolism. However, basal serum insulin values were not different from those of controls. These data suggest that chronic hyperprolactinemia has an hyperglycemic effect and has a significant influence on glucose handling by the liver, through reduced glycolysis. PMID- 2101788 TI - Age-related changes in growth hormone and prolactin messenger RNA levels in the rat. AB - Growth hormone (GH) secretion declines with age, while prolactin (PRL) secretion increases in rats. The age-related changes in the pituitary GH and PRL mRNA levels in the Wistar Tw rat were studied at 6, 12 and 18 months of age by cytoplasmic dot hybridization. Hormone and mRNA concentrations were expressed as values per micrograms GH-cell or PRL-cell DNA. Concurrent decrease in GH concentrations and GH mRNA concentrations with age was observed in female rats, but not in male rats. GH mRNA concentrations (per microgram GH-cell DNA) in male rats at 12 and 18 months of age were 88 and 66% of those at 6 months of age, but there was no difference. GH mRNA concentrations in female rats at 12 and 18 months of age were 51 and 53% of those at 6 months of age. A concurrent decrease in PRL concentrations and PRL mRNA concentrations was observed in both male and female rats. PRL mRNA concentrations (per microgram PRL-cell DNA) in male rats at 12 and 18 months of age were 37 and 18% of those at 6 months of age. PRL mRNA concentrations in female rats at 12 and 18 months of age were 51 and 31% of those at 6 months of age. Pituitaries in 12- and 18-month-old females contained more PRL and PRL mRNA than those at 6 months of age. These increases in PRL and PRL mRNA contents may result from the increase in the number of PRL cells, although each PRL cell had less PRL and PRL mRNA. These results suggest that the age related changes in pituitary GH and PRL levels occurred at the transcription level of GH and PRL syntheses, and that the age-related changes in GH-cell and PRL-cell populations are responsible for the changes in GH and PRL secretions. PMID- 2101789 TI - Decreased levels of steroid 21-hydroxylase [P450(c21)] and its mRNA in an adrenocortical adenoma associated with 21-hydroxylase deficiency. AB - Adrenocortical adenoma incidentally found in a 37-yr-old female patient, with simple virilizing form of 21-hydroxylase deficiency, was studied. Cultured adenoma cells revealed excessive secretion of 17 alpha-hydroxyprogesterone in response to 10(-8) M ACTH, compared with those of 11-deoxycortisol and cortisol, which indicated impaired activity of the 21-hydroxylase. To elucidate the molecular mechanisms of this defective 21-hydroxylase in the adenoma, we analyzed the gene encoding specific cytochrome P450 (P450c21) for steroid 21-hydroxylation and its expression. DNA and RNA were extracted from the adrenal adenoma and were hybridized with a probe of human P450c21 gene, by Southern and Northern blot analysis. In Southern blot analysis with Taq I, Bgl II or Bam HI, there was no difference between the pattern of restriction fragments in DNA from the adenoma and normal peripheral leucocytes. Northern blot analysis of the adenoma showed the same size of P450c21 mRNA as in the normal adrenal gland, but the amount was low--about a half that of the normal adrenal. In Western blot analysis with polyclonal antibody to P450c21, only a small amount of P450c21 protein was detected in the adenoma, although it was found to be of the same molecular weight as that in the normal adrenal gland. In view of these findings it is conceivable as one of possibilities that a mild and small mutation in the structural or promotor region of the P450c21 gene may cause the decreased 21-hydroxylase activity in this adenoma. PMID- 2101790 TI - Effects of various doses of growth hormone on serum total cholesterol, phospholipid, and bile acid in a patient with cholestasis. AB - To determine whether growth hormone (GH) has any impact on the hyperlipidemia seen in cholestatic patients, graded doses of GH in the sequence of 0.1, 0.2, 0.4, and 0.6 u/kg every other day were administered sc to a patient with Alagille syndrome. Serum total cholesterol, phospholipid, and bile acid were measured. The serum levels of all three decreased markedly after GH administration and the lowest levels were observed on the second day after the GH dose of 0.4 u/kg. However, they increased thereafter despite the administration of an increased dose of GH; especially the serum bile acid level returned to the initial value by day 8. Serum levels of SM-C and fT3 were not correlated with the changes in total cholesterol, phospholipid, and bile acid after GH administration. We suggest that the administration of GH may affect the state of hyperlipidemia seen in cholestatic patients. PMID- 2101791 TI - Effects of neuromedin B and GRP-10 on gastrin and insulin release from cultured tumor cells of a malignant gastrinoma. AB - A study relating to gastrin release from gastrinoma cells by neuromedin B and C terminal decapeptide of gastrin releasing peptide (GRP-10) has not yet been reported. Therefore, we studied the effects of neuromedin B and GRP-10 on gastrin release from cultured dispersed cells prepared from both the primary tumor in the pancreas and the metastatic tumor in the liver from a case of malignant Zollinger Ellison syndrome. Both the primary and metastatic tumors obtained by a curative operation contained similar concentrations of gastrin and glucagon, whereas the primary tumor contained 10 times more insulin than the metastatic tumor. Gastrin release from cultured cells of both tumors was suppressed by 0.1 and 10 nM neuromedin B and tended to be suppressed by 0.1-10 nM GRP-10. However, insulin release from cultured cells of the pancreatic tumor was stimulated by GRP-10, but not by neuromedin B. These results might suggest that receptor function for the bombesin family peptides is abnormal in gastrinoma cells in both primary and metastatic tumors, and that a major source of insulin secretary cells is the contaminated normal islet cells in the primary tumor. PMID- 2101792 TI - Effects of insulin-like growth factor-I on insulin and glucagon release from isolated perfused rat pancreas. AB - The infusion of recombinant insulin-like growth factor I (IGF-I) causes a decrease in plasma glucose and insulin. In this study we examined whether or not IGF-I directly affects islet hormone release by means of a rat pancreas perfusion system. A superphysiologic concentration of IGF-I (2 nM) elicited a slight but significant decrease in insulin release under the perfusate glucose concentration of 120 mg/dl. A pharmacological concentration of IGF-I (200 nM) significantly suppressed the increase in insulin release in response to an increase in the perfusate glucose concentration (from 4.5 mM to 12.8 mM), but did not affect the decrease in insulin release in response to a decrease in the perfusate glucose concentration (from 6.9 mM to 2.8 mM). Glucagon release was not influenced by IGF I in these experiments. These results suggest that IGF-I potentially inhibits the insulin release from islet B-cells directly, but its pathophysiological significance may be slight considering its partial inhibition at superphysiologic concentrations and its stable plasma level. PMID- 2101794 TI - Stromal fat content of the parathyroid gland. AB - The proportion of stromal fat cells to parenchymal cells in 100 normal parathyroid glands was determined by the image analyzing computer technique. The parathyroid glands were resected at the time of thyroidectomy in 86 patients with thyroid tumors. None of the patients had any evidence of parathyroid dysfunction preoperatively. In the histologic sections of the parathyroid glands, the average percentage of stromal fat cell content was 38%. The percentage of stromal fat cells was correlated with the age and the body constitution of the patients, but the percentages of fat cells varied widely among glands in the given age and body constitution ranges. It was therefore not possible to discriminate a normal parathyroid gland from an abnormal gland solely on the basis of microscopic determination of stromal fat cell content. PMID- 2101793 TI - Differential sensitivity of pancreatic beta-cells to phorbol ester TPA and C kinase inhibitor H-7 in nonpregnant and pregnant rats. AB - In order to elucidate the possible role of C-kinase in exaggerated insulin release in pregnancy, the effects of phorbol ester TPA and a C-kinase inhibitor H 7 were investigated using the isolated perfused pancreas from nonpregnant and pregnant rats. At the termination of perfusion, the insulin content of the perfused pancreas was determined to estimate insulin biosynthesis. Insulin release from the perfused pancreas was markedly augmented by 20 nM TPA in the presence of 4.4 mM glucose in pregnant rats, but not in nonpregnant rats. When glucose concentrations in the perfusate were raised to 16.7 mM, insulin release from the perfused pancreas was profoundly enhanced in pregnant rats. TPA further augmented insulin release, but the insulin content was not affected by TPA. In contrast to the considerable effect of TPA in the presence of 4.4 mM glucose, the potentiating effect of TPA on insulin release was rather weaker in pregnant than in non-pregnant rats in the presence of 16.7 mM glucose. The release of insulin induced by 16.7 mM glucose was inhibited by the addition of 100 microM H-7 in nonpregnant rats, whereas insulin release from pregnant rat pancreases was not altered. Thus, the effect of TPA and H-7 on insulin release can be more clearly observed in the beta-cells of nonpregnant rats than those of pregnant ones when maximal concentrations of glucose are used as a stimulant. Exaggerated insulin release caused by glucose in pregnancy may be due to already fully activated C kinase in the beta-cells. PMID- 2101795 TI - Effects of beta-hydroxy butyric acid on insulin binding to its receptor and on autophosphorylation of the receptor. AB - We examined the effects of beta-hydroxy butyric acid (B-OH-butyrate) on insulin binding to its receptor and on autophosphorylation of the receptor in vitro. The affinity of isolated rat adipocyte insulin receptors was significantly increased by B-OH-butyrate at neutral pH. Similar results were obtained with soluble insulin receptors prepared from hepatocytes. Autophosphorylation of insulin receptor, however, was not affected by OH-butyrate at neutral pH. These results suggested insulin resistance in ketoacidosis is not caused by an interaction between B-OH-butyrate and the insulin receptor. PMID- 2101796 TI - The effect of estrogen and progesterone on the volume-pressure curve of the uterine ampulla in late pregnant rats. AB - Volume-pressure curves of the uterine ampullae, taken on day 17 of pregnancy from intact pregnant and ovariectomized, vehicle- or estradiol and/or progesterone treated pregnant rats, during infusion of Ca-free Tyrode's solution containing EGTA at a constant rate were determined, and the effects of the steroids on the Vz value, which was obtained by extrapolating the linear part of the curve to zero pressure, and compliance were evaluated. Both the parameters examined were decreased by ovariectomy. Treatments with estradiol or progesterone alone did not but the steroids combined restored Vz to the level of intact pregnant rats, and partially restored compliance. The significance of the development of Vz by estrogen and progesterone for the maintenance of pregnancy is discussed. PMID- 2101798 TI - Quantitative determination of high molecular weight alkaline phosphatase in patients with colorectal cancer by polyacrylamide gel electrophoresis. AB - We present a new method for the quantitative determination of high molecular weight alkaline phosphatase (ALP). This method consists of electrophoretic separation on polyacrylamide, incubation of the ALP isoenzymes with substrate, gel drying and quantitative evaluation by densitometric measurement. This method separates high molecular weight ALP from the other isoenzymes. Precision of the method is calculated by the coefficient of variation ranging from 1.2 to 9.5% for samples with different high molecular weight ALP values. The diagnostic sensitivity for detecting colorectal cancer is 60%. PMID- 2101797 TI - Sex differences in the subunits of glutathione-S-transferase isoenzyme from rat and human kidney. AB - Glutathione-S-transferase (GST) isoenzymes were purified from cytosolic preparations from kidneys of male and female rats and kidney cortical specimens from 2 male and 1 female human subjects. GST isoenzyme expression was analyzed by SDS-PAGE, measurement of catalytic activities with specific substrates and determination of their subunits by ELISA and Western blotting using specific antibodies. GST from female rat kidneys showed a preponderance of subunits 3 and 4; levels of these isoenzymes were 3-4 times greater in females than in males. Levels of subunits 1 and 2 were 1.5-2 times greater in the male rat kidneys. Additional minor bands at 24 and 22 kD were observed in GST preparations from both male and female rat kidneys while a band at 25.3 kD was observed only in the male rat kidney. These bands did not react with antibodies to GST 1-1, GST 2-2 or GST 3-4. Both male and female human kidney samples contained GST isoenzymes comparable to the near-neutral (25-5 kD) and basic forms (25 kD) of GSTs found in human liver. In addition a 28-kD band was present in GST preparations from both male and female human kidneys. Additional bands at 29 and 25.2 kD were present only in male human kidneys. Both the kidney cytosol and the total GSTs prepared from female rats shared 2- to 4-fold greater activity with 1,2-dichloro-4 nitrobenzene, ethacrynic acid and trans-4-phenyl-3-buten-2-one than those from males. The measurement of specific subunit amounts by ELISA were in agreement with these results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101799 TI - Fate of alpha-1,4-glucosidases and cathepsin D in the rat epididymis after vasectomy. AB - Short-term vasectomy was studied in adult male rats in order to ascertain whether cytosolic or lysosomal hydrolases were differently affected 100 days after vas ligation. The secretory form of alpha-1,4-glucosidase remained unchanged while the lysosomal form of the enzyme and also cathepsin D increased in the cytosol of both caput and cauda epididymis. This set of data demonstrates for the first time that a triggering mechanism which stimulates lysosomal activity is present all along the rat epididymis. Disposal of the continuous influx of spermatozoa from the testis could therefore require both an active and a passive process. PMID- 2101800 TI - Sialidase activity in rimantadine-resistant and -sensitive influenza A viruses. AB - Rimantadine-resistant and -sensitive influenza A variants were assayed for their sialidase (neuraminidase, EC 3.2.1.18) activity. The kinetic parameters determined (pH optimum, stability against different pH values, thermal stability, activity on methylumbelliferyl-alpha-D-N-acetylneuraminic acid, N acetylneuraminyl-lactose, fetuin and bovine submandibular gland mucin as substrates, Km with the former substrate, inhibition by two competitive inhibitors, and behavior towards amantadine) revealed the same results for both variants of the virus. Thus, it can be deduced that resistance to rimantadine does not influence the sialidase activity of influenza A virus. PMID- 2101801 TI - Comparison of arylsulfatase C and steroid sulfatase from human placenta and liver. AB - Human placental and hepatic arylsulfatase C (ASC) were purified to homogeneity and about 1,000-fold, respectively. Placental ASC hydrolyzed sterol sulfates at the same active site, whereas the major hepatic ASC did not. This major hepatic ASC isozyme was more thermolabile than placental ASC and steroid sulfatase from both placenta and liver. It was not precipitated by anti-bovine ASC IgG which quantitatively precipitated both placental ASC and steroid sulfatase activities from placenta and liver. A minor hepatic ASC isozyme with similar electrophoretic mobility to the placental enzyme copurified with the major hepatic ASC and is likely responsible for the steroid sulfatase activity in this organ. Hence, placental ASC and steroid sulfatase are biochemically and antigenically identical to hepatic steroid sulfatase. In contrast, the major hepatic ASC is a distinct protein whose catalytic and structural properties differ from all the above enzymes. PMID- 2101802 TI - Ethanol decreases the level of sulfhydryl compounds in red blood cells and changes their hematological pattern in rats. AB - The level of sulfhydryl compounds in red blood cells (RBCs) and plasma and some haematological parameters were investigated in rats treated with ethanol for 4 weeks (daily dose of 6g/kg, 30% w/v, p.o.). After ethanol ingestion, the significant decrease of non-protein - SH groups were observed in RBCs and plasma. In treated rats, the mean corpuscular haemoglobin concentration (MCHC) was decreased and the mean corpuscular volume (MCV) was increased. There is a positive correlation between these two parameters and decreased content of sulfohydryl groups in RBCs. PMID- 2101803 TI - Activation antigens in patients with Sjogren's syndrome. AB - We report findings of a study of two receptors on mononuclear cells from patients with Sjogren's syndrome (SS). The two receptors, interleukin-2 receptor (IL-2), transferrin receptor (TfR), were identified using monoclonal antibodies anti-IL-2 and OKT9. We found that the IL-2 and TfR positive cells were significantly higher on mononuclear cells (MC) from peripheral blood (PB) of patients with SS than in healthy controls. The study revealed that the IL-2 and TfR positivity reflects systemic immune activation and correlates closely with the activity of SS. PMID- 2101804 TI - Clinical value of cytomorphologic, immunologic and cytogenetic investigations of acute leukaemias. AB - The valuability of immunophenotyping of acute myeloid and lymphoid leukaemias in comparison to morphological and cytochemical classification were approached in 56 cases. In the case of acute myeloid leukaemias the immunophenotyping by monoclonal antibodies CD14, CD13, CD33 was less informative concerning the subtypes of the disease. The clinical diagnosis can be achieved on the basis of cytochemical investigation alone. In contrast, the diagnosis of lymphoid leukaemias requires all information obtained by immunophenotyping by a series of monoclonal antibodies CD3, CD2, CD4, CD8, CD1, CD19, CD20, CD21 and CD10. On the other hand, the monoclonal antibodies are essential in differentiation of the very immature myeloid and lymphoid leukaemias. This is of great importance from the clinical point of view for determining the therapy. Molecular genetic studies based on the characterisation of the state of gene rearrangement of immunoglobulin and T-cell receptor beta chains have basic importance in the confirmation of the result of immunophenotyping and in the determination of leukaemias of unknown origin. PMID- 2101805 TI - Hairy cell leukemia. Immunological study. AB - The study has been performed on peripheral blood and splenic malignant cells from 16 patients with hairy cell leukaemia (HCL). The cell surface markers were identified by rosette techniques and using monoclonal antibodies (m Ab). The surface markers' expression of the hairy cells (HC) varied. The E receptors, the T-cell antigens, the HLA-DR antigens and smIgG were either expressed or not according to the affected organ, the progress of illness, or the treatment. The surface pattern changed sometimes in the same patient during the progress of illness. These observations demonstrate that HCL is a unique disease with malignant cells characterized by a marked variability of the cell surface markers. To demonstrate the ability of hairy cells to bind labile smIgG, the cells were studied by affinity chromatography on SpA-Sepharose 6MB and by ES rosette assay. The percent of cells bound on SpA-Sepharose varied between 6% and 66%, representing the hairy cells with labile-bound smIgG. With affinity chromatography it was also possible to separate the hairy cells with a special phenotype: T3+ T4+ T8+ T11+ surface membrane labile-bound IgG+ (11gG+) FcR+, HLA DR+ EACD+ (Ripley rosette forming cells), resembling a normal subset of large granular lymphocytes (LGL). The percentage of these cells varied between 60% and 86% of the bound cells. These observations suggest that in HCL, the malignant transformation might involve a common progenitor for the B, T and LGL lineages, the hairy cell being a hybrid type of malignant cell. Its main immunological peculiarity is the marked mobility of the surface membrane structures and hence the lability (plasticity) of the surface markers' expression. PMID- 2101806 TI - Distribution and scatter of yeast cell phagocytosis by human monocytes in an improved glass surface assay. AB - The assessment of yeast cell phagocytosis by glass-adherent monocytes was improved by ultrasonication of yeast cells prior to the experiments in order to prevent aggregation, restriction of measurements to completed engulfment regardless of the number of peptides ingested, and stopping of phagocytosis before counting by maintained cooling and the addition of EDTA. The modifications provided a reduced dispersion of individual values, increased engulfment of yeast cells, and decreased numbers of yeast cells only adherent to the monocyte membrane. The improvement made the method more convenient for the study of engulfment by monocytes. PMID- 2101807 TI - Efficient cell mediated lysis of human erythrocyte target cells is mediated by a human glycophorine A specific murine monoclonal antibody. AB - A human glycophorine A specific murine monoclonal antibody mediates the antibody dependent killing of antibody sensitized human erythrocytes by human K cells (monocyte-free mononuclear cells). The overall level of killing is lower than that mediated by conventional, human anti-D antibodies but it is significant on each target cell. PMID- 2101808 TI - Serum cholinesterase variants in Spanish blood donors. AB - A population of 783 blood donors has been analyzed for serum cholinesterase variants resistant to dibucaine and fluoride. The incidence of these cholinesterase variants in the blood donors was lower than that found in other European countries. PMID- 2101809 TI - Adhesive properties of blood cells. AB - The adhesive interactions of the cells with each other and with the extracellular matrix (ECM) are important for their normal growth and differentiation. Currently, very little is known concerning the adhesive and cell recognition factors that maintain cell-to-cell contacts in haemopoietic tissues. The majority of peripheral blood cells are known to possess an ability to interact with each other (aggregation phenomenon) or with various artificial materials, which has important implications for medicine, particularly in the fields of thrombosis, vascular prosthetics and dialysis. On the other hand, recent studies indicate that blood cells can interact with the main important components of ECM, such as collagen, fibronectin, etc. These data, as well as the newly discovered receptor structures for various adhesive proteins on the surface of blood cells suggest that the haemopoietic tissue has a diverse function involving interaction with the ECM. PMID- 2101811 TI - The dental assistant shortage. PMID- 2101810 TI - A provisional fixed bridge with moveable abutments. PMID- 2101812 TI - Peer review. PMID- 2101813 TI - Preventing child abuse. PMID- 2101814 TI - Endodontic patient education. PMID- 2101815 TI - [PG-Universal retraction system. Theoretical aspects and clinical application. 2. Controlled incisor retraction]. PMID- 2101816 TI - [Vertical and sagittal relapse following surgical-orthodontic correction of distal bite position. Cephalometric longitudinal study]. PMID- 2101817 TI - [Evaluation of orthodontic treatment results]. PMID- 2101818 TI - [Resistance and elasticity of orthodontic wires from considerations of super elastic materials]. PMID- 2101819 TI - [Properties of super elastic wires and their influences]. PMID- 2101820 TI - [Predictability using the "Dentofacial Planner Version 4.22 A" of soft tissue changes following adult orthodontic treatment]. AB - For the prediction of profile changes following orthodontic treatment the computer program "Dentofacial Planner" (DFP) which bases on cephalometric measurements is available. The object of this study is to analyse the precision of the DFP version 4.22 A (release Feb. 89). The material of the study consists of the lateral cephalograms of 33 patients treated for maxillary incisor protrusion. In order to evaluate the ensuing profile changes certain cephalometric parameters are measured pre- and post-therapeutically. They are compared to the values predicted by the DFP. Statistical analysis yields the following results: 1. Clinically acceptable precision was found for seven of the 20 cephalometric parameters. 2. In two of the six parameters stated to be stationary by the DFP notable changes were found in reality. 3. The most accurate prognosis was made for the upper lip profile; the least precision was found for the lower lip. According to the manufacturer the results of this study will be included in alternations of the DFP program so as to achieve improvements in the criticized areas. PMID- 2101821 TI - Retinyl ester (vitamin A ester) and carotenoid composition in human liver. AB - Surgical liver biopsy samples from seven diseased and five healthy human subjects, 3-33 years of age, were analyzed by reversed-phase high-pressure liquid chromatography for retinol (vitamin A alcohol), retinyl esters (vitamin A esters), and carotenoids. Total liver vitamin A values ranged from 7.8 to 2860 nmol/g liver (2.2 to 817 micrograms/g). As a percentage, liver retinol decreased with increasing liver reserves of vitamin A. Retinyl palmitate was the predominant vitamin A ester (57 to 83 mole%) in all samples, with retinyl stearate (5.5 to 11.4%), oleate (4.9 to 17.2%), and myristate plus palmitoleate (pair not resolved; 3.3 to 11.9%) next most common. Lesser amounts of retinyl linoleate, linolenate, and arachidonate were found. Normal livers had significant amounts of several carotenoids: lutein (0.2 to 16.2 nmol/g), lycopene (10.2 to 55.1 nmol/g), alpha-carotene (3.0 to 7.3 nmol/g), and beta carotene (5.8 to 25 nmol/g). Total carotenoid values ranged from 26.5 to 67 nmol/g in normal liver samples. There was no correlation between liver vitamin A and individual or total carotenoids in normal livers. PMID- 2101822 TI - Plasma vitamin A levels in cattle in response to large doses of vitamin A. AB - A dose response procedure was developed for evaluating vitamin A status and utilization in cattle. This could be useful for evaluating diets, vitamin A stores and homeostatic control of vitamin A. Three experiments were designed to determine: 1) size of vitamin A dose required to increase plasma vitamin A concentrations; 2) time after dosing when plasma vitamin A concentrations peak, and 3) if changes in plasma vitamin A concentrations are useful in assessing dietary vitamin A utilization. Using twenty-four steers and heifers, the first two experiments showed that 30X or 40X daily vitamin A requirement (daily requirement calculated as X = body weight in kilograms times 55 International Units of vitamin A) given orally was sufficient to cause plasma vitamin A concentrations to rise 20 hours after dosing. Plasma vitamin A concentrations increased (P less than .01) from 57 to 81 micrograms/dl and 64 to 84 micrograms/dl after a 30X or 40X treatment, respectively. Twenty-X daily requirement resulted in a slight increase after 20 hours (P greater than .05). Seventy-two feedlot steers were used in experiment three to determine if diet affects vitamin A dose response. Variations in feed intake, monensin in the diet or a single dose of vitamin E did not cause significant changes in plasma vitamin A response to vitamin A dosage. Steers receiving monensin had higher initial plasma vitamin A concentrations, but no differences were observed after dosing. Results indicate that dose responses may be useful in assessing dietary vitamin A utilization. PMID- 2101823 TI - Plasma calcitriol in chickens producing strong and weak egg shells and the response of hens to exogenous calcitriol. AB - Calcitriol (CAL) regulates intestinal calcium transport by inducing an increase in membrane phosphatidylcholine (PC) and calbindin. A positive correlation has been reported between shell gland PC and egg shell strength. Three experiments were conducted to test the hypothesis that the improvement in egg shell strength associated with increased PC is mediated via changes in the concentration of CAL. Sera from aged laying hens, identified as either strong (SES) or weak (WES) egg shell producers, were obtained from blood samples collected at 16 h after oviposition and assayed for CAL. Laying hens were injected (i/m) with 1.0 or 0.4 micrograms CAL/d for 28 d. Serum CAL in the WES hens was 70% of that in the SES hens (P less than .05). Hens producing extremely weak shells did not respond to 0.4 micrograms CAL/d for 10 d. Administration of CAL did not improve egg shell strength nor was serum CAL increased when WES hens were molted and shell gland PC increased. The results show that serum CAL is lower in aged hens producing weak egg shells but shell strength is not responsive to exogenous CAL and increased shell gland PC in WES hens after molting is not associated with higher serum CAL. PMID- 2101824 TI - Determination of alpha-tocopherol in plasma, platelets and erythrocytes of type I and type II diabetic patients by high-performance liquid chromatography. AB - Vitamin E (alpha-tocopherol) concentrations of plasma, platelets and erythrocytes were determined by HPLC in insulin-dependent (type I) and age-matched non-insulin dependent (type II) diabetic patients and in two control groups. Plasma alpha tocopherol levels were significantly increased in diabetic patients compared to control groups. Platelet and erythrocyte alpha-tocopherol levels were not significantly different in type I and type II diabetics as compared to their respective control groups, but differed from one another. Plasma vitamin E concentrations showed a significant correlation with plasma cholesterol and apoprotein B concentrations in different groups. The alpha-tocopherol/cholesterol and alpha-tocopherol/apoprotein B ratios in plasma were higher in diabetic patients, as were triglyceride contents. Platelet vitamin E levels were not significantly correlated with plasma concentrations. These findings suggest that vitamin E activity is altered in diabetic patients but that no diet supplementation seems necessary. PMID- 2101825 TI - Plasma vitamin E response in sheep dosed intraruminally or intraduodenally with various alpha-tocopherol compounds. AB - A total of 24 sheep were used to study two routes of vitamin E administration: intraruminal (IR) and intraduodenal (ID). For each route of administration, 12 sheep were divided into 3 groups of 4, and each group received one of the following vitamin E treatments (mg/kg body weight): treatment 1, D-alpha tocopherol (60 mg); treatment 2, D-alpha-tocopherol acetate (70 mg); treatment 3, DL-alpha-tocopherol (90 mg). The results showed that two major indices of bioavailability, i.e. concentration maximum and the area under the plasma concentration time-curve, were higher following IR administration than ID administration for all three vitamin E compounds used in this experiment. In sheep dosed intraruminally no difference was observed between the three vitamin E preparations in their plasma vitamin E response. For the ID administration the peak of plasma vitamin E concentration was lower after D-alpha-tocopherol acetate dosing than with the other two preparations. The results indicated a beneficial effect of rumen environment on the availability of vitamin E supplements. PMID- 2101826 TI - Retention and utilization of thiamin by gravid and non gravid rats with varying dietary thiamin supply. AB - The intention of this paper was to examine a retention of thiamin by gravid and non gravid rats and to test also whether there is an anabolism of the gravids. For this purpose a trial with 176 rats was designed in a two-factorial model (2x11x8) with the factors gravid versus non gravid and 11 different dietary thiamin concentrations of 0/0 (gravid/non gravid), 0.8/1, 1.7/2, 3.3/4, 6.7/8, 13.3/16, 20.0/24, 26.7/32, 100/120, 1000/1200, 10,000/12,00o mg thiamin per kg diet. The daily thiamin intake of the gravids and non gravids was the same. The experiment lasted until the 20th day of gestation. Liver, brain and musculus quadriceps, the reproductive organs and also the whole carcass were examined for their thiamin contents. At the beginning of the experiment 12 animals were sacrificed to get their starting contents. Liver thiamin retention was significantly influenced by the dietary supply, also by gestation and by the interaction of both factors. For the gravids, a mean daily anabolism of 1.5 micrograms occurred in the liver. In brain a negative retention of 4-8% occurred during the experiment, which was significantly less in the gravids. In muscle dietary supply was of significant influence, gestation, however, decreased muscle retention in gravids. In whole carcass the gravids retained 81 micrograms and the non gravids 61 micrograms (P less than 0.05). Anabolism occurred from 3.3 mg dietary thiamin per kg (46 micrograms daily intake) and plateaued at about 30 mg or 1.5 micrograms daily until 100 ppm dietary thiamin. Thiamin utilization remains below 10% in all groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101827 TI - Vitamin C and nutritional status of institutionalized and noninstitutionalized elderly women in Rome. AB - A cross-sectional study on 64 institutionalized and 65 noninstitutionalized elderly women has been undertaken. The age range was 60 through 90 years. Vitamin C status was assessed by serum ascorbic acid measurement and the nutritional status was evaluated by a three-day dietary record and main anthropometric measurements. Mean concentration of ascorbic acid was 1.03 mg/dl in the noninstitutionalized and 0.67 mg/dl in the institutionalized group (p less than 0.001). A serum ascorbic acid level less than 0.2 mg/dl was found in one (1.5%) and seven (10.9%) subjects respectively (p less than 0.03). Mean intake of vitamin C was 104.1 mg/d in the former and 87.3 mg/d in the latter group (p = NS), being less than 45 mg/d in 16 living at home and 11 institutionalized women. Serum ascorbic acid level did not correlate significantly to dietary nutrient intake but correlated to activity of daily living level (r = 0.29), vitamin C intake (r = 0.23), ideal body weight (r = -0.15), relative body weight (r = 0.15) and body mass index (r = 0.14). Suggestions are made concerning a higher intake of vitamin C and a more careful catering to improve the health status of the elderly people living in large institutions. The authors also suggest to include the serum ascorbic level determination in the assessment of the general health status of the elderly. PMID- 2101828 TI - Serum ascorbic acid and HDL cholesterol in a healthy elderly Japanese population. AB - The relationships between HDL cholesterol and serum ascorbic acid were examined in 79 male and 96 female healthy elderly Japanese, aged 60 and over. A significant positive correlation between serum HDL cholesterol and ascorbic acid was observed both in males (r = .243, p less than 0.05) and in females (r = .376, p less than 0.01). The results of multiple regression analyses indicated that serum ascorbic acid is a predictor of serum HDL cholesterol accounting for about 5% and 11% of its total variation in male and female subjects, respectively. The effect of age, BMI, status of physical activity, alcohol ingestion and cigarettes consumption, serum triglycerides and total cholesterol were taken into account as potentially confounding variables. PMID- 2101829 TI - Effect of dietary vitamin C on ascites in broiler chicks. AB - A total of 480 day-old broiler chicks were divided randomly into 4 equal groups, each of 4 replicates, and reared for two weeks. To their rations, which contained sodium chloride at 2.5% ascorbic acid was added at the rate of 0, 150, 300 and 450 mg/kg for groups 1, 2, 3 and 4 respectively. Incidences of ascites cases were 20.8, 10.8, 7.5 and 7.5% for the groups 1, 2, 3 and 4 respectively. When vitamin C was added to their rations body weights were increased significantly, but feed consumption remained unchanged. There were no significant differences in water consumption or body moisture. The total serum protein was significantly increased. The packed cell volume was only increased in the chicks that had received 450 mg vitamin C/kg of feed and there were no significant differences in the ascorbic acid content of the plasma. It was concluded that the addition of vitamin C to the chicks' rations reduces the incidence of ascites caused by toxic dietary levels of sodium chloride. PMID- 2101830 TI - Dietary restriction augments erythropoiesis in mice. AB - Previously, we have reported that a 40% dietary restriction caused microcytic and short-lived erythrocytes without anemia in mice (Internat. J. Vitr. Nutr. Res. (1989) 59, 406-412). To elucidate the mechanism of these phenomena, the effects of dietary restriction on the proliferation of erythroid precursor cells were investigated. In the diet restricted mice, a striking increase of erythropoietin (EP - responsive erythroid precursor cells without increment of EP was observed. Remarkable increases in the numbers of femoral nucleated cells and erythroid stem cells (CFU-S) were also observed in the diet restricted mice. Furthermore, the percentage of femoral CFU-S in DNA synthetic stage (S phase) revealed remarkably higher levels in the diet restricted mice than in the control mice. Our results strongly suggest that the microcytic change of erythrocytes in the diet restricted mice may be attributed to the increased number of erythroid precursor cells without an increment of hemoglobin synthesis and that the avoidance of becoming anemic from the short-lived erythrocytes in the diet restricted mice may be caused by a vigorous erythropoiesis. PMID- 2101831 TI - Influence of dietary intake of energy and carbohydrate on the proportion of saturated and monounsaturated fatty acids in adipose tissue of middle aged men. AB - The fatty acid composition of subcutaneous tissue has been determined in a population sample of apparently healthy middle aged men from Southern Italy. Dietary appraisal has been carried out by evaluating the usual pattern of food consumption during the year preceding the interview. The whole population sample was subdivided into three tertiles on the basis of the energy intake by the different individuals. The proportion of adipose tissue polyunsaturated fatty acids was relatively low in the high energy tertile III and high in the low energy tertile reflecting parallel differences in the intake of polyunsaturated fatty acids. The percentage of monounsaturated fatty acids (mainly oleic acid) was relatively high (p less than 0.01) and that of saturated fatty acids (mainly palmitic acid) relatively low (p less than 0.05) in the high energy tertile (III) as compared to the low energy tertile (I); these differences were independent of the amount and type of dietary fatty acids. Total energy was positively correlated (r = .87, p less than 0.01) to carbohydrate intake (g/day). Dietary carbohydrates (g/day) were inversely related to adipose tissue saturated fatty acids (r = -.40, p less than 0.001) and directly correlated to adipose tissue monounsaturated fatty acids (p = .40, p less than 0.001). Carbohydrate intake was related to adipose tissue monounsaturated and saturated fatty acids independently of daily energy intake. On the other hand when the influence of dietary carbohydrates was eliminated, no correlation was detectable any longer between energy intake and adipose tissue fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101832 TI - Effects of dietary hyperlipidemia-hypercholesterolemia on rat erythrocytes. AB - We report in the present work that membrane fluidity in erythrocytes from rats under alimentary hyperlipidemia-hypercholesterolemia is slightly diminished despite the fact that in these cells the cholesterol/phospholipid molar ratio is nearly 45% higher than in erythrocytes from control animals. In addition, the erythrocyte count in the rats given the high-fat, high-cholesterol diet was normal. Only a slight reticulocytosis was observed in these animals although their erythrocytes showed a marked decrease in their ability to extrude sodium actively. A tentative explanation for these results is proposed on the basis of other findings suggesting cellular compensatory mechanisms. PMID- 2101833 TI - Effect of irradiation and germination on trypsin inhibitor and protein content of chickpea (Cicer arientinum L.). AB - Effect of irradiation (0.05-0.20 kGy) and subsequent germination on trypsin inhibitor activity (TIA) and protein content of chickpea, was studied. The results revealed a significant linear relation (r = 0.981 to -0.992) between the loss of TIA and germination time, and the rate of TIA destruction increased with irradiation dose (p less than 0.05). Maximum destruction (43.8%) of the TIA occurred on germination for 120 hr of 0.20 kGy sample (from 330.0 to 185.3 TIU/g). Initially protein content was 21.7% and the value significantly increased to maximum levels of 27.5% and 27.9% in distilled and tap water respectively during germination for 120 hr of 0.10 kGy sample (p less than 0.05). Protein contents were not affected by irradiation. PMID- 2101834 TI - Selective removal of retinoids and palmitic acid from microsomes by fatty acid binding protein and cellular retinol binding protein. AB - Studies were conducted to explore the effect of mouse liver cytosolic proteins enriched in fatty acid binding protein or cellular retinol binding protein on the removal of palmitic acid and retinoids from microsomal membranes. When the soluble proteins were incubated with mouse liver microsomes containing (14C)palmitic acid or (3H)retinoids, it was observed that fatty acid binding protein removed selectively the fatty acid and retinyl ester, whereas the retinol was mainly removed by cellular retinol binding protein. PMID- 2101835 TI - Sickle cell anemia and major organ failure. AB - Major organ failure in sickle cell anemia is the direct consequence of the sickle cell evoked vasculopathy. Major organ failure is first clinically apparent as autosplenectomy, then during childhood presents as cerebral infarction and atrophy, and finally culminates in young adulthood as end stage renal failure (glomerulosclerosis), sickle chronic lung disease, intracranial hemorrhage, retinopathy, disabling leg ulcers, and generalized osteonecrosis. The vascular damage begins years before the overt clinical symptoms are apparent with no pain to act as a signal. Organ damage is progressive and irreversible. The rate of progression is genetically controlled from birth. Except for the management of life-threatening infections that are associated with the non-functioning spleen, disease expression has not been altered by therapy. The focus of future clinical investigations must be the prevention of the vasculopathy and tissue damage which is induced by the sickle red cell. PMID- 2101836 TI - Hb Davenport or alpha 2(78)(EF7)Asn----His beta 2. AB - Hb Davenport is a new, stable alpha chain variant, that was detected in two members of a Caucasian family living in Iowa. Hematological data were within normal limits. It is characterized by an Asn----His replacement at position alpha 78. Mild acidic hydrolysis of the large alpha T-9 peptide, separation of the resulting fragments by reversed phase high performance liquid chromatography, and sequence analysis of a few of these peptides greatly facilitated the identification of this substitution. PMID- 2101837 TI - Unusual molecular basis of Hb H disease in the Azores Islands, Portugal. AB - An Azorean family with Hb H disease (10% Hb H) was studied in order to elucidate its molecular basis. DNA studies on the patient only revealed a 4.2 kb "leftward" deletion of paternal origin which implies the co-inheritance of a nondeletional alpha-thalassemia determinant. Restriction endonuclease and oligonucleotide analysis allowed the exclusion of five point mutations: initiation codon (at both alpha 1- and alpha 2-globin genes), IVS-I donor splice junction pentanucleotide deletion, codon 125 CTG----CCG substitution, and Saudi Arabian polyadenylation signal mutation. These findings suggest that the molecular basis of this form of Hb H disease is probably different from those described previously. PMID- 2101838 TI - Low quantities of Hb Boyle Heights or alpha 2(6)(A4)Asp----O beta 2 observed in three members of a Caucasian family. PMID- 2101839 TI - The thermal stability of Hb O-Indonesia [alpha 116(GH4)Glu----Lys]. PMID- 2101840 TI - Hb Jacksonville [alpha 2 beta 2(54)(D5)Val----Asp]: a new unstable variant found in a patient with hemolytic anemia. PMID- 2101842 TI - [Abstracts of papers presented at XXXII annual meeting of the Japan Society of Smooth Muscle Research]. PMID- 2101841 TI - Beta-thalassemia repository. PMID- 2101843 TI - [Peritonitis in continuous ambulatory peritoneal dialysis. Microbiological and clinical evaluation]. AB - In 1976, Popovich et al. described a technique of peritoneal dialysis using bottled dialysate. Later Oreopoulos et al. modified the technique by using plastic bags. But peritonitis still is a major and potentially serious complication of peritoneal dialysis. We have evaluated a) microbiologic diagnostic methods for infectious peritonitis, b) incidence of etiologic agents, and c) the evolution during antimicrobial treatment. Eighteen patients with chronic renal failure of diverse causes were followed from initiation of the CAPD program since January 1981 until June 1988. There were 80 episodes of infectious peritonitis during 17 patient-years of dialysis with an overall incidence of peritonitis of 4.7 episodes/patient-year. The total volume centrifuged technique and culture of sediment showed a sensibility of 85% in 73 episodes where cultures were obtained. The 59.1% of episodes of peritonitis were caused by gram negative bacilli; 11.6% were due to Acinetobacter calcoaceticus and Gram positive cocci accounted for 37.3%. These results are different from those found in other countries because most of our patients had received antimicrobial agents which probably changed their body flora, some did not have manual ability, others were of bad hygienic habits and finally, all of them had frequent contact with hospital environment. The species most frequently isolated were coagulase negative staphylococci (12.8%), probably from patients' skin flora. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2101844 TI - [Salla disease (sialuria, Finnish type). New clinical presentation in the 1st Argentine report]. AB - Studies in three sibs from an Argentine family, aged 29, 18 and 9 years, suffering from a severe neurological disease, revealed in the two older brothers (the third died), ultrastructural changes in cellular vacuolization in diverse peripheral tissues (conjunctival, gum and skin biopsies) and in blood lymphocytes. These data were suggestive of mucopolysaccharidosis, mucolipidosis or glycoproteinosis. However, the activity of lysosomal enzymes, the excretion of mucopolysaccharides and oligosaccharides reactive to orcinol, as well as the search for aspartylglucosaminuria gave normal values. The main biochemical finding was the detection of a substantial urinary increase of a unique resorcinol-positive compound, which by thin-layer chromatography was identified as N-acetylneuraminic acid (NANA-Free) and when quantified by the thiobarbituric acid method previously passed through a gel filtration column (Sephadex G-15) or through ion exchange resins, showed a NANA-Free concentration about 15 times higher than in controls of similar age (Table 2). The ultrastructural findings (Figs. 3-5), the hypersialuria and the present clinical state of these patients (Table 1, Figs. 1, 2) were compatible with Salla disease, a rare lysosomal storage disease originally observed in Finland. The precocity and severity of the neurological damage in our patients were evident since birth and without maturing accomplishments in their first years, contrary to the progressive neurological regression described for the classical syndrome. Based on these facts we suggest that the Argentine patients would constitute a new clinical form of Salla disease. PMID- 2101845 TI - [Spontaneous remission of retroduodenal sac fundus syndrome (sump syndrome)]. AB - The Sump syndrome is an infrequent complication of a choledochoenterostomy (choledochoduodenostomy or choledochojejunostomy) performed for recurrent stone disease: a sump or pit develops at the retroduodenal section of the choledochus between the enterostomy and papilla where stones, lithogenic bile and gastrointestinal contents accumulate. This may lead to abdominal pain, pancreatitis and cholestasis and/or cholangitis when sludge obstructs the enterostomy. Surgical treatment has been replaced by endoscopic papillotomy. The major interest of this experience was that regarding migration of the stones to intestine, the spontaneous resolution could be documented in two patients; in other two cases, because of contraindications in one case and for refusing therapy in another, the stones still remain at the retroduodenal choledochus. In a follow up of two to eight years there is a favorable evolution without any surgical or endoscopic treatment of the papilla. PMID- 2101846 TI - [Treatment of blepharospasm with botulinum toxin]. AB - Blepharospasm is a relatively frequent cranial dystonia which may be seen either alone or related to orofacial-mandibular dystonia (Meige's syndrome). In its maximum degree it can cause functional blindness.Twelve patients with blepharospasm (4 essential and 8 Meige's syndrome) who had been previously treated unsuccessfully with drugs (trihexyphenidyl, biperiden, carbamazepine, lithium, baclofen, lisuride, imipramine, clonazepam and butyrophenones) were treated for 12 months with periocular injections of botulinum toxin (BOTOX). A "low" dose of 12,5 U per eye was employed. With this dose, eleven out of twelve patients experienced significant improvement which lasted from five to fifteen weeks. The only nonresponder obtained complete relief upon duplicating the dose. The only side effect was uni or bilateral ptosis in six patients which improved completely in seven to twenty one days. One patient developed a peripheral facial palsy with complete remission in nineteen days. No systemic side effects were noted. There was only one desertion from this study due to depression enhanced by prolonged (21 days) ptosis. All patients (including the deserter) agreed that treatment with BOTOX provided more relief than any other previous therapeutic method. Our results confirm those obtained by others but a more prolonged study is needed to better evaluate long term effects. PMID- 2101847 TI - [AIDS and pregnancy: a case of mother-child transmission]. AB - We report the case of a 4 month old baby in an advanced stage of HIV infection with AIDS according to the CDC definition. The HIV-infected mother was sexually promiscuous and a drug addict. The timing and route of the infection are speculative. The child was born by cesarean delivery, did not receive blood or blood products and was not breast-fed. It is postulated that the most probable route of HIV infection in this child was intrauterine vertical transmission. PMID- 2101848 TI - [POEMS syndrome: report of a case and review of the literature]. AB - A case of POEMS Syndrome of six years of evolution is reported. This syndrome is characterized by Raynaud phenomenon, polyneuropathy, edema, anasarca, papilledema, osteosclerosis and lymphadenopathy with the histopathology of Castleman's disease, hypothyroidism, hypogonadism, cutaneous sclerosis, hyperpigmentation, axillary alopecia and the presence of urinary lambda light chains. A bone marrow biopsy did not show plasmocytic infiltration and there was no evidence of extramedullary plasmocytoma. Methylprednisone was given at the dose of 1 mg/kg/day and subjective and objective improvement was observed. The edema and anasarca disappeared as well as the lymphadenopathies; muscle strength improved and the patient was able to walk without aid. Papilledema persisted. The pathogenesis of this syndrome remains unknown; some of the symptoms have been attributed to paraprotein deposits in peripheral nerves, high capillary permeability due to vascular alterations, accelerated conversion of androgen to estrogen, or to the production by plasma cells of a toxic substance. Mortality is related to complications of the polyneuropathy. Some patients in whom POEMS syndrome was associated, or not, with myeloma were treated with chemotherapy and/or radiotherapy with different responses; in others, corticosteroids were of short lived benefit. Our patients remains well after 42 months treatment with 20 mg methylprednisone every other day. PMID- 2101849 TI - [Left cranial nerve deficit and ipsilateral hemiplegia in a 46-year-old man]. PMID- 2101850 TI - [Ceftizoxime: a new aminothiazolyl-syn-methoxy-iminocephalosporin]. PMID- 2101851 TI - [Cathepsins: their role in tumor invasiveness]. PMID- 2101852 TI - [Ethics committees]. PMID- 2101853 TI - [Ethical basis for cancer treatment in children]. PMID- 2101854 TI - [Collagen glycosylation, restriction of articular mobility, ageing and diabetes]. PMID- 2101855 TI - [Creutzfeldt-Jakob disease]. PMID- 2101856 TI - [Psychiatry and psychology]. PMID- 2101857 TI - [Second malignant tumor in children. Report of 22 cases]. AB - Between 1965 and 1988, at the Children's Hospital of Buenos Aires, 22 children developed two successive malignant tumors of different histology. The first tumor was diagnosed between 3 months and 12 years of age: 13 retinoblastoma, 2 rhabdomyosarcoma, 2 non-Hodgkin lymphoma, 2 Hodgkin disease, 1 brain stem glioma, 1 endodermal sinus tumor and 1 Ewing sarcoma. Familial cancer was registered in 6 patients. Children were treated with surgery, intensive chemo and radiotherapy. The second malignancy developed after 2 to 13 years: 10 osteosarcoma, 2 Ewing sarcoma, 2 rhabdomyosarcoma, 2 glioblastoma, 1 medulloblastoma, 1 synoviosarcoma, 1 fibrosarcoma, 1 thyroid carcinoma, 1 acute lymphoblastic leukemia and 1 acute myeloblastic leukemia. In 17 patients, the tumor developed in irradiated field. There was no evidence of the first tumor and only 1 patient was still under chemotherapy. Oncologic treatment was frustrating for these second tumors and 18 children died. Three are alive with no evidence of disease at 2 years, 2 years and 4 months and 3 years after diagnosis. One patient was lost to follow-up. It if postulated that second malignant tumors are consecutive to genetic predisposition and/or to the oncogenic effect of chemo and radiotherapy. The intensity of each treatment modality must be reduced as much as possible to obtain survival while limiting the secondary effects. PMID- 2101858 TI - [Clinical therapeutics in arterial hypertension]. PMID- 2101859 TI - [Collection of cases in relation to clinical trials of fluconazole in Germany]. AB - Fluconazole is a new antifungal agent from the class of triazoles for systemic treatment of fungal infections caused by Candida or Cryptococcus. From September 1988 to June 1990, fluconazole has been made available free of charge in a clinical trial for the treatment of patients who failed to respond to conventional therapy or in whom conventional therapy was limited due to side effects etc. (compassionate usage program). Overall, 1,188 patients were entered including 79 with cryptococcal meningitis, 665 with life-threatening and 444 with non-life-threatening candidosis. The following results were found in an interim evaluation of 254 cases: The therapeutic success (cure and improvement) was 43% in patients with cryptococcal meningitis, 54% in life-threatening candidosis and 67% in non-life-threatening candidosis. PMID- 2101860 TI - [Prophylaxis and therapy of fungal infections with fluconazole in patients after bone marrow transplantation]. AB - In an open study 31 patients undergoing bone marrow transplantation for various haematological diseases received fluconazole as prophylaxis or treatment of fungal infections. In 26 of these patients an antecedent oral prophylaxis with polyene antimycotics had failed to prevent infections with Candida species. Five of the 31 patients received fluconazole as primary prophylaxis because of non compliance for polyene antimycotics. Fluconazole was administered orally at a daily dose of 100 mg and 200 mg, respectively (n = 29), or intravenously at a dose of 100 mg and 400 mg (n = 2). Cure or efficient prophylaxis was achieved in 22/31 patients (71%) after a median of 52 (9 to 546+) treatment days. In three patients (10%) Candida was eradicated but the infection reappeared 14-28 days after cessation of the drug; in 6 patients (20%) the infection was persistent or progressive. Four patients developed lethal Aspergillus infection while on fluconazole medication. A moderate and reversible elevation of liver function tests under therapy was observed in 9 patients and was possibly attributable to fluconazole in 3 of them (10%). One patient developed tremor which resolved after cessation of fluconazole. No other adverse drug reactions could be noted. We conclude that fluconazole is a relatively safe and effective drug for the prevention and treatment of superficial and, possibly, deep Candida infections in severely immunocompromised patients. It is presumably without preventive value in Aspergillus infections. PMID- 2101861 TI - [Systemic candidiasis in patients after kidney and heart transplantation]. AB - Nosocomial and other severe infections are able to cause life-threatening complications in organ transplant recipients. Unter such conditions the treatment will be successful only in early status of infection. Fluconazol (Diflucan) has been used in the treatment of candidosis in cardiac and renal transplant patients with good results, and lack of adverse effects. PMID- 2101862 TI - [The therapy of Candida esophagitis in AIDS patients with fluconazole]. AB - Esophageal candidosis was found endoscopically in 135 of 496 AIDS patients with upper gastrointestinal symptoms. Vomiting, dysphagia and retrosternal pain were the leading symptoms. Endoscopy showed different stages of esophagitis with Candida patches as early changes up to severe esophagitis with hemorrhage. 36 patients were treated with fluconazole orally or intravenously administered (100 mg per day). In 33 of 36 patients clinical, endoscopic and microbiological results were good with complete cure of the lesions after 7, 14 or 21 days of treatment. In 3 patients with wasting syndrome and severe opportunistic infections a resistance to the drug was discussed because of lack of sufficient therapy results. Maintenance therapy seems to be necessary to prevent relapses. PMID- 2101863 TI - [Systemic candidiasis in intensive care patients after antibiotic therapy]. AB - The authors report fluconazole treatment of 19 I.C.U. patients in critical situations. 9 of these patients had septic multiorgan failure. All patients had received long term antibiotic treatment for at least seven days. The difficulties in clinical and laboratory diagnosis of systemic candidosis which requires treatment are discussed. All patients showed good response to fluconazole treatment concerning the opportunistic mycotic infection; none of the patients died because of systemic candidosis. Severe side effects were not observed. PMID- 2101864 TI - [Comparison of oral fluconazole and amphotericin B prophylaxis against fungal infections in the neutropenic phase of patients treated with antileukemic agents]. AB - Forty patients with acute leukemia (age 16-71 years, 13 females, 27 males) with induced neutropenia due to chemotherapy received either 50 mg fluconazole or 800 mg amphotericin B per day orally as prophylaxis against fungal infection. Nasal and genital swabs, mouth washings, urine, stool and blood serum were taken for mycological and serological examination before and weekly during one episode of neutropenia (less than 10(9) granulocytes/l) per patient. The quantitative determination of the yeast concentration in stool specimens demonstrated that amphotericin B led to intestinal yeast count reduction in only one third of the patients and could not prevent the increase of the intestinal yeast flora in another third of the patients. Beyond that the quantitative determination of yeast colonization in oropharynx, genital region, blood and stool did not prove to be a reliable tool for evaluating the host-fungus relationship during neutropenia. On the other hand mycoserology reflected episodes of candidosis well. 19 patients treated with fluconazole showed only minor titer increases. In 21 patients treated with amphotericin B, four fungemias were found: two by both hemagglutination (HAT) and immunofluorescence (IFT), one by IFT and one by antigen detection (Ramco Cand-Tec) alone. In only one of these cases yeast cells were released in urine. From these results is concluded that control of serology is essential in studies of that type and that fluconazole seems to provide better protection from candidosis than amphotericin B during induced neutropenia. PMID- 2101865 TI - [Cryptococcosis in AIDS: therapeutic concepts]. AB - Cryptococcosis is the most common life-threatening mycosis with AIDS. The combination therapy based on amphotericin B and flucytosine is furthermore the therapy of first choice, even after introduction of fluconazole. With a therapy maintained over a period of 6 weeks the combination is nearly always successful; a shorter treatment period leads to minor treatment success. Since no elimination of the pathogen is possible in cryptococcosis with AIDS a permanent relapse prevention is necessary. In this prevention strategy fluconazole is highly effective and at present the drug of first choice; it is as effective as amphotericin B. An additional advantage is the possibility of oral application. PMID- 2101866 TI - [The significance of fluconazole (diflucan) in the therapy and prevention of candidiasis and cryptococcosis]. PMID- 2101867 TI - [The laboratory diagnosis of deep localized candidiasis]. AB - A survey on the presently used methods for isolation and differentiation of Candida yeasts as well as on serological methods is presented. The difficulties of the pathognomonic evaluation of laboratory parameters are discussed. PMID- 2101868 TI - Bioethics and knowledge. AB - The acquisition of knowledge must be regarded as the first duty, as affirmed by Claude Bernard and Jacques Monod. It occupies a place in the forefront of other duties--respect for the individual and his liberty and dignity--to which the duty of knowledge must be subordinated. An attempt must be made to reconcile these diverse obligations. These three situations are described by stressing the importance of the principles that govern these studies: respect for the individual; respect for science; restriction of human experiments to what is strictly necessary; scrupulous assessment of the balance of risks and advantages; the human body is not an object of commerce; free and informed consent; solidarity between men. PMID- 2101869 TI - Fanconi's anemia: genetic and molecular aspects of the defect. AB - Several features of Fanconi's anemia (FA) are reported: relative inefficiency in the processing of DNA cross-links and monoadducts, hypomutability at the two loci analysed, complementation of the cytogenetic defect by cocultivation with mouse cells and homology of the FA group A with the mouse cellular mutant MCS attempts to clone and characterise a DNA fragment which complements the defect. The relation between observed features and predisposition to leukemia are discussed. PMID- 2101870 TI - Diagnosis of Fanconi's anemia by flow cytometry. AB - FA is a progressive bone marrow aplasia genetically transmitted by a recessive autosomal gene or genes. In our laboratory, cytogenetic diagnosis is based on evaluation of the chromosomal breakage of mitotic cell derived from patient blood cell cultures and sensitized by nitrogen mustard (NM). We have observed, in parallel with this test, fluctuations of the cell cycle of PHA- stimulated peripheral blood lymphocytes from FA patients as compared with controls. FA cells treated with NM show a dramatic and significant increase in G2/M phase after 72 hr in vitro culture, compared with untreated or control cells (normal controls and non-FA patients). This test is rapid and simple, as it consists in staining cells with a DNA dye (propidium iodide), followed by a flow cytometry analysis of the cell cycle phases. Our results in twelve patients are correlated with the cytogenetic results. PMID- 2101871 TI - Regulation of human megakaryocytopoiesis. AB - Megakaryocytopoiesis is a complex, highly regulated cellular and biologic process which leads to the production of platelets. The proliferation of megakaryocyte (MK) progenitors is mainly regulated by interleukin-3, granulocyte-macrophage colony-stimulating factor and an as yet uncharacterized MK colony-stimulating factor. The maturation of MKs to produce platelets is essentially regulated by interleukin-6 and thrombopoietin. Optimal megakaryocytopoiesis is controlled by appropriate combinations of positive and negative influence. Megakaryocytopoietic inhibition is controlled by transforming growth factor beta, platelet factor 4 and its related proteins, interferon-alpha and -gamma. PMID- 2101872 TI - The bcl-2 gene and 14;18 translocation in lymphoproliferative disorders. AB - The 14;18 translocation is generally considered a good marker for follicular lymphomas and it has also been suggested that it is of prognostic significance in this disease. It has also been claimed that the bcl-2 protein can be detected by immunohistology only in lymphoma carrying t(14;18). We have raised antibodies to the bcl-2 protein and shown that expression of the protein is not specific for the translocation and have also demonstrated that there is no correlation between prognosis and the presence of the translocation. It is also evident that t(14;18) is present only in about two-thirds of follicular lymphoma patients (and is found in 20-30% of diffuse lymphomas). PMID- 2101873 TI - Towards a mouse model for sickle cell disease: HB SAD. AB - Very recently a high expression of human hemoglobin S, which causes sickle cell disease, has been obtained in transgenic mice. We have constructed a modified beta S gene, beta SAD which carries two additional mutations in order to induce polymerization of transgenic hemoglobin when diluted by endogenous mouse Hb. The transgenic SAD mice are not anemic but exhibit a low percentage of irreversible sickle cells. Sickling is induced by deoxygenation of erythrocytes in vitro. In addition, the anemia of neonates and the low incidence of SAD animals in the progeny suggest a deleterious effect of SAD Hb during development. Finally, hypoxia induces a high mortality in SAD adults suggesting the induction of vaso occlusive events. PMID- 2101874 TI - Splenic B-cell lymphoma with villous lymphocytes (SLVL). A lymphocytic lymphoma simulating hairy cell leukemia. A study of 8 cases. AB - Splenic B cell lymphoma with circulating villous lymphocytes (SLVL) is a lymphoproliferative disorder characterized by the presence in the peripheral blood of atypical B-lymphocytes with hairy appearance. Although the clinical features with massive splenomegaly, absence of peripheral lymphadenopathy and blood cytopenia may mimic hairy cell leukemia (HCL), precise analysis of the morphologic and immunologic features allow differential diagnosis between these two entities. Bone marrow and spleen histology resemble the pattern in chronic lymphocytic leukemia (CLL). We studied 8 patients with this entity illustrating the difficulty of diagnosis between SLVL and HCL. PMID- 2101875 TI - Access to the fetus. PMID- 2101876 TI - Some new quantitative aspects of fetal erythropoiesis. AB - Ultrasound guided fetal blood sampling performed for diagnostic purpose has allowed us to determine the evolution of normal hematological parameters i.e. all nucleated cells, red blood cells, platelets, hemoglobin, mean corpuscular volume in 2,680 normal fetuses from the 18th to the 30th week of gestation. Differential blood counts were estimated. We determined normal circulating level of erythropoietic progenitors cells, which is three times higher than in cord blood at birth. Erythropoietin levels were very low and were not modified during the second and the third trimester of pregnancy. All these new data reveal fundamental quantitative differences in the hematopoietic system of fetal on adult subjects. PMID- 2101877 TI - HLA DQ alpha/beta molecule associated with the susceptibility to insulin dependent diabetes mellitus. A model for HLA/autoimmune disease association. AB - We have proposed a molecular model of susceptibility to Insulin-Dependent Diabetes Mellitus (IDDM) based on the proportional expression at the cell surface of the following susceptible (S-S) HLA-DQ heterodimere composed of a chain DQ alpha Arg 52 positive (S) and a chain HLA-DQ beta Asp 57 negative (S). All other DQ alpha/beta chains associations are considered as protective molecules. This model allows a predictive scale of risk for the disease. PMID- 2101878 TI - Endothelial proteases stimulated by blood platelets. AB - Endothelial cells secrete a protease which is activated in the extracellular medium by platelets. This protease PECAP, degrades casein and fibrinogen, and its characteristics differentiate it from the other known blood and vascular proteases. PMID- 2101879 TI - Microdissection and microcloning of human banded chromosomes. AB - A new microdissection and microcloning procedure of human banded chromosomes has been recently described. These microtechniques allow the construction of band specific DNA libraries, providing a large number of DNA probes for the identification of gene sequences. These methodologies are particularly efficient to reach chromosomal regions involved in human genetic diseases including cancer. PMID- 2101880 TI - Fluorescence in situ hybridization on metaphase chromosomes with biotinylated probes. In situ hybridization, biotin labeling, cosmids, gene mapping, oncogene amplification. AB - In situ hybridization on metaphase chromosomes have been used to localize specific nucleic acid sequences. Initially, the nucleic acid probes were labeled isotopically. Over the past few years, non isotopic techniques have considerably progressed, and are being applied to a large spectrum of biological and clinical problems. PMID- 2101881 TI - Cat-scratch disease bacteria. AB - Cat-scratch disease is a benign inoculative lymphoreticulosis, related to the presence of a polymorph bacillus, Warthin-Stary silver stained, Gram negative as assessed by Brown-Hopp staining. It is found in the capillary walls and in macrophages bordering the lymph node sinusoids at the site of inoculation, in regional subacute adenopathy before softening, in internal organs and blood cultures of systemic infections, occurring more often in immuno-compromised patients. These bacteria have been demonstrated in subcutaneous vascular nodules, near to histiocytoid hemangioma in AIDS patients; these lesions are very similar to early stage Kaposi's sarcomas. This bacteria is provisionally listed as G 1492 by the Center for Disease Control. PMID- 2101882 TI - Allyl protection of O6 position of 2'-deoxyguanosine. AB - Allyl serves as the protecting group for O6 position of guanosine. The deblocking is easily performed by brief treatment with a palladium(O) catalyst and a nucleophile. PMID- 2101883 TI - Oligonucleotides with pyrene fluorophore at the sugar fragment: synthesis and properties in binding to complementary polynucleotide. AB - Oligonucleotides with 1-pyrenylmethyl substituent at the designated sugar residue were synthesized by using 5'-dimethoxytrityl 2'-(1-pyrenylmethyl)uridine 3' phosphorobisdiethylamidite 1. It was shown that the pyrene-oligonucleotides have enhanced affinity in binding to the complementary polynucleotide sequence. The fluorescence yield and life time of the pyrene-oligonucleotide was drastically enhanced when bound by the complementary polynucleotide. PMID- 2101884 TI - Preparation and duplex-to-single strand transition of the fully complementary duplex of d(G4).d(C4) in aqueous solution. AB - The d(G4) and d(C4) molecules in the single stranded state were synthesized by the phosphotriester method and purified. The full duplex of tetramer d(G4).d(C4) was prepared by expending about a month. The duplex-to-single strand transition was observed by UV-spectroscopy. A standard hypochromic effect was observed, which is different from some experimental results reported previously. PMID- 2101885 TI - Probing salt-induced and supercoiling-induced B-Z junctions in DNA by bisulfitemethoxyamine. AB - Salt-induced and supercoiling-induced B-Z junctions in pWR756, a plasmid containing (GC)16, were probed with bisulfite-methoxyamine, a modification reagent specific for single-stranded nucleic acids. The modification sites were analyzed with S1 nuclease and the modified cytosines were determined from termination sites of DNA chain elongation by DNA polymerase. The results showed that most accessible cytosines are the same for both types of B-Z junctions. PMID- 2101886 TI - Chemical synthesis of the 5'-terminal structure of U1 RNA. AB - A new method for the synthesis of N2,N2-dimethylguanosine (DMG) is developed by reductive C-S bond cleavage by use of tributyltin hydride. An improved method for the synthesis of the key intermediate (1) for construction of the 5'-terminal structure of U1 RNA, which has a trimethylated cap (TMG) structure at its 5' end, is also described. By the use of 1, several TMG-capped ribonucleosides and oligonucleotides were synthesized. PMID- 2101887 TI - Assignments of the iminoproton resonances of Bombyx mori tRNA(UCCGly) and the comparison of its structure and stability with those of tRNA(GCCGly). AB - Most of the iminoproton resonances in the 1H-NMR spectrum of Bombyx mori tRNA(UCCGly) have been assigned by the sequential NOEs. Any peak which indicates the presence of the tertiary GC base pair between the D and T loops could not be detected. The effects of temperature and the addition of magnesium ions and spermine on the 1H-NMR spectrum of this tRNA were examined. From the temperature change, it was found that the acceptor stem and the D stem in Bombyx mori tRNA(UCCGly) are equally stable even in the absence of magnesium, which is different from tRNA(GCCGly) where the D stem is not so stable. PMID- 2101888 TI - Watersoluble synthetic nucleic acid analogs--polyethyleneimine derivatives containing nucleic acid bases--conformation and interactionwith nucleic acids. AB - Water soluble polyethyleneimine derivatives containing nucleic acid bases were found to interact with polynucleotides, DNA, RNA. The conformational change by formation of complex was observed by CD spectra and was discussed with the hypochromicity in UV spectra. The rates of interactions between nucleic acid bases in polymers were slow as shown by UV spectra, but the conformational changes of the polynucleotides were fast as shown by CD spectra. In the case of the uracil derivative (PEI-Hse-Ura), high value of CD spectra [theta] 2.80 = -8.0 x 10(-4) for the complex with DNA might be caused by psi type conformation of DNA. PMID- 2101889 TI - Discriminator base and anticodon as a tRNA identity element. PMID- 2101890 TI - Recognition of tRNA identity determinants by aminoacyl-tRNA synthetases. AB - By analyzing aminoacylation activities of variants of isoleucine tRNAs and glutamic acid tRNA from Escherichia coli, it was found that the anticodons are the major determinants for "identities" of these tRNAs. It was also shown that the post-transcriptional modifications are essential to aminoacylation of these tRNAs. Interactions between the tRNAs and the aminoacyl-tRNA synthetases were analyzed by NMR spectroscopy. PMID- 2101891 TI - An NMR study on the conformation of the chromomycin-d(GGGGCCCC)2 complex. AB - The conformation of the chromomycin-d(GGGGCCCC)2 complex in aqueous solution was studied by NMR spectroscopy. The NMR spectrum of the complex indicated that the chromomycin binds as a symmetry-related dimer to the minor groove of the central four residues of d(GGGGCCCC)2. The drastic conformational change in the central four residues of d(GGGGCCCC)2 from the B form family to the A-form was demonstrated by the characteristic NOEs and coupling patterns. The change seems to be indispensable for accommodation of the bulky chromomycin dimer in the minor groove. On the basis of the intermolecular NOEs between chromomycin and d(GGGGCCCC)2, the structure of the complex has been constructed and refined by energy minimization. PMID- 2101892 TI - Helical structures of nucleic acid-lipid conjugates: formation and morphology of helical structures from dimyristoyl-5'-phosphatidylribonucleosides. AB - Phospholipid-ribonucleoside conjugates containing two myristoyl groups and a ribonucleotidyl group, dimyristoyl-5'-phosphatidylribonucleosides have been synthesized and their self-organization and morphology have been investigated. Dimyristoyl-5'-phosphatidylribonucleosides spontaneously assembled to form various types of helical strands. PMID- 2101893 TI - Phosphonate and thiophosphate nucleotide analogues in studies of some enzyme reactions. AB - Enzymes which cleave P-O bonds can be blocked by phosphonate analogues of biological phosphates. alpha-Fluorophosphonates are more electronegative at the bridging carbon than simple methylenephosphonates which improves their use for the study of enzymes. Thus, the beta,gamma-difluoromethylene analogue of ATP is a viable substrate for (2----5)An synthetase which converts it into (2----5)An species having a 5'-beta,gamma-difluoromethylene-trisphosphate. This binds strongly to RNase L but does not activate it. The unsymmetrical Ap4Aases from Artemia and lupin are strongly inhibited by P2,P3-fluoromethylenebisphosphonate- and by P1,P4-dithiophosphate-analogues of diadenosyl-5',5"-P1,P4-tetraphosphate while anomalous, non-regiospecific cleavage of some P2,P3-bridged mimics is observed. Certain such analogues inhibit both platelet aggregation in vitro and arterial blood-clotting in rabbits. Separation of the diastereo-isomers of P1,P4 dithiophosphate analogues of Ap4A is achieved using reverse-phase hplc which provides direct access to beta,gamma-CHF-bridged analogues of ATP with resolved stereochemistry at the CHF centre. PMID- 2101894 TI - Synthesis of novel 6-substituted acyclouridine derivatives and their anti-HIV-1 activity. AB - To improve the anti-HIV activity of 1-[(2-hydroxyethoxy)methyl]-6 (phenylthio)thymine (HEPT), a variety of its analogues were synthesized. Introduction of SR group to the C-6 position was carried out based on LDA lithiation followed by the reaction of aryl- or alkyl disulfide. An addition elimination reaction of a 6-phenylsulfinyl derivative was used for synthesizing the analogues having OR or NHR group at the C-6 position. The C-5 modified derivatives were synthesized mainly based on LTMP lithiation of a 6-phenylthio derivative. Modification at the 2- or 4-position was also carried out. Some compounds prepared in the present study showed higher activity than HEPT. PMID- 2101895 TI - Highly stereoselective synthesis of carbocyclic oxetanocin and its related compounds from bicycloamides. PMID- 2101896 TI - Synthesis and biological activities of 8-substituted 2-5A analogues. AB - The 8-(2-hydroxypropyl)-adenosine and 8-hydroxy adenosine-substituted analogues of 2-5A and it's derivatives were synthesized and their biological activity was evaluated in mouse L cell extracts. The 8-hydroxy adenosine-substituted analogues (i.e. pppAOH2'p5AOH2'p5'AOH, pAOH2'p5'AOH2'p5'AOH, pppA2'p5'A2'p5'AOH, pA2'p5'A2'p5'AOH) inhibited protein synthesis with a relative activity compared to the parent 2-5A. Further, the greater interest is the observation that the corresponding 5'-monophosphate had to inhibitory activity. However, 8-(2 hydroxypropyl)-adenosine substituted analogue (pAHPr2'p5'AHPr2'p5'AHPr) can not about bound as well as parent 2-5A. PMID- 2101897 TI - Synthesis of unusual nucleosides and evaluations of their biological properties. PMID- 2101898 TI - Total chemical assembly of genes. AB - An artificial gene comprising 183 base pairs has been assembled by template directed condensation of 35- to 53-membered oligodeoxyribonucleotides with cyanogen bromide as a condensing agent. The reaction is complete within several minutes at 0 degree C in buffer. The resulting gene was cloned into M13mp11 and sequenced using the Sanger sequencing procedure. PMID- 2101899 TI - Uranyl ion-catalyzed synthesis of several 8-substituted 2'-5'-oligoadenylates, and their properties. AB - We have synthesized 2'-5' linked oligomers from 8-substituted adenosine-5' phosphorimidazolides using uranyl ion catalyst. 8-amino derivative, as highly susceptible to hydrolysis, gave short chained oligomers in a low yield, while the rest of 8-substituted or unsubstituted derivatives gave the corresponding oligomers in high yields. Properties of 8-substituted 2'-5' oligomers were studied applying spectrometer and through enzymatic digestion. PMID- 2101900 TI - Phosphonylmethoxyalkyl derivatives of purine as inhibitors of human hepatitis B virus DNA synthesis. AB - A selected number of antiviral compounds which have been previously shown to inhibit the replication of DNA viruses or retroviruses were examined for their inhibitory effects on human hepatitis B virus (HBV) DNA synthesis. The assay system was based on the use of a human hepatoblastoma cell line (HB611) that continuously synthesizes HBV DNA. The following phosphonylmethoxyalkyl-purine derivatives were found to inhibit HBV DNA synthesis: 9-(2-phosphonyl methoxyethyl)-2',6'-diaminopurine (PMEDAP), (S)-9-(3-hydroxy-2 phosphonylmethoxypropyl)adenine (HPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA). PMEDAP, HPMPA and PMEA not only inhibit HBV DNA synthesis in HB611 cells but also duck hepatitis B virus (DHBV) DNA and core antigen synthesis in primary duck hepatocytes. PMID- 2101901 TI - Identification of DNA degradation products by antitumor antibiotic, esperamicin. AB - Esperamicin A1 is a DNA-damaging agent characterized by a unique ten-membered ene diyne core. We studied the detailed reaction mechanism by using synthetic DNA oligomers. The cleavage site and activity depend on the sequence of the oligomers. d(GGATCC) and d(GGTACC) were cleaved by the drug while d(CCATGG) and d(CCTAGG) were not cleaved under the present conditions. d(GGTACC) gave two major 5'-fragments. The result of partial nuclease digestion experiments suggests that these products are trimer and pentamer with a modified 3'-end. PMID- 2101902 TI - A new assay to measure RNA N-glycosidase activity. AB - We have developed a convenient procedure to measure the activity of Ricin A-chain and other enzymes with RNA N-glycosidase activity. The method is based on the use of a tritiated oligoribonucleotide as a substrate. The enzymatic activity is directly determined by measuring the release of adenine from the substrate. This method should prove useful in the study of the molecular mechanism of action of Ricin A and other RNA N-glycosidases. PMID- 2101904 TI - Constraction of a subtracted cDNA library using oligo(dT)-latex. AB - An efficient method for constraction of subtracted cDNA library was developed using oligo(dT 30. Latex and PCR. This method improved the chances for identifying cDNA clones corresponding to scarce class of mRNA that is expressed differentially during cellular growth and differentiation. PMID- 2101903 TI - Invention of anti-Leishmania drugs on the basis of the nucleoside structures. AB - 3'-Deoxy-3'-fluoroinosine is a potent inhibitor for the growth of the promastigote form of Leishmania tropica and Leishmania donovani. In culture, the EC50 values of 3'-deoxy-3'-fluoroinosine are 2.3 x 10(-7) and 1.0 x 10(-6) M for the promastigotes of L. tropica and L. donovani, respectively. It is less toxic towards mouse mammary tumor FM3A cells: the EC50 value is 2.0 x 10(-4) M. 3' Deoxy-3'-fluoroinosine is metabolized by Leishmania promastigotes to give 3' deoxy-3'-fluoroadenosine-5'-triphosphate. This metabolic conversion provides a mechanism for the parasite-selective toxicity of 3'-deoxy-3'-fluoroinosine. PMID- 2101905 TI - C-C bond formation at the 3'-position of nucleosides by the use of their enol esters. AB - Nucleosides having an enol ester structure in the sugar portion were synthesized and their reaction with several types of electrophiles were carried out. This furnished a new method for constructing C-C bond at the 3'-position. PMID- 2101906 TI - Analysis, identification and determination of urinary modified nucleosides of cancer and AIDS patients. AB - Modified nucleoside levels in urine samples collected before and after surgery from seven patients with malignant gastrointestinal cancer were examined by the reversed-phase HPLC method. Those of an AIDS patient, a breast cancer patient, and pooled normal urines were also compared. To monitor the effects of therapy on cancer patients, the levels of modified nucleosides, especially t6A and MTA, were found to be fairly effective. In an AIDS patient, the levels of most of the nucleosides exhibited remarkable increases compared to normal urine. PMID- 2101907 TI - Switch-function of amino sugar on elsamicin A, a DNA binding antitumor antibiotic. AB - There are a considerable number of DNA binding natural products equipped with amino sugar residues. The amino sugar of elsamicin A significantly takes part in DNA binding and antitumor activity. In addition, we found that an acetylation of the amino group on elsamicin A sugar portion plays an important switch-function for the activity of elsamicin A. The biological implication of this switch has been discussed. PMID- 2101908 TI - Synthesis and biological activity of novel carbocyclic nucleosides. AB - The syntheses of several novel carbocyclic nucleosides which incorporate the cyclopentene moiety of neplanocin A will be presented. These include modified pyrimidine derivatives of the very potent antitumor agent cyclopentenyl cytosine and carbocyclic analogues of the ketohexose nucleosides psicofuranine and psicofuranosyl cytosine. PMID- 2101909 TI - Quantification analysis of human alpha-globin gene. Mutation in 5'-splice junction sequence and alpha-thalassemia. AB - Nucleotide sequence of the exon-intron junction in human alpha-globin gene was analyzed by quantification method proposed previously. Using sample score of 9 nucleotide sequence at 5'-splice site, we examined strength of the splice signal. We further studied a mutant of alpha-thalassemia, where pentanucleotide deletion occurs around 5'-splice junction of the first intron. This mutation abolishes the normal 5'-splice site completely, but activates a cryptic site lying in the first exon. Such a behaviour was well explained in terms of our sample scoring scheme. PMID- 2101910 TI - Conformation and properties of hammerhead-type RNA enzymes. AB - We designed a hammerhead-type RNA enzyme system which consists of three ribooligonucleotide strands (1-3), synthesized these oligomers and their analogues, and examined conformation and properties of the RNA complexes. Imino proton NMR spectra of the complexes were measured and the signals were assigned by comparison with the spectra of some model duplexes. Examination of a complex containing a G----I mutation (Y = I) revealed that the 2-amino group of the third guanosine residue in the loop 1 (L1) plays an important role for maintaining both the activity and loop conformation. PMID- 2101911 TI - Chemical synthesis of oligoribonucleotides for structural studies. AB - Large-scale synthesis of oligoribonucleotides has been performed successfully on a solid support by the phosphoramidite approach using levulinyl and tetrahydrofuranyl protection for the 5'- and 2'-hydroxyl groups respectively. A hexamer containing inosine and four fragments of a hammerhead-type ribozyme have been synthesized on a 10 mumol scale for structural studies by NMR spectroscopy and X-ray crystallography. PMID- 2101912 TI - Thermodynamics and kinetics for the helix formation of the P3 region in Tetrahymena ribozyme. AB - The thermodynamic and kinetic results for the helix formation of the oligonucleotides, GACCGUCA and UGUCGGUC, which correspond to the sequence of the P3 region in Tetrahymena ribozyme are reported. The kinetic result suggested that the melting mechanism of the duplex of the oligonucleotides consisted of at least two steps because of a UU mismatch. PMID- 2101913 TI - Diels-Alder reaction of nucleosides; synthesis of bicyclic sugar adenosine derivatives. PMID- 2101914 TI - Synthesis of a new potent antitumor nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D- arabinofuranosylcytosine. PMID- 2101915 TI - Search for novel RNA catalysts. An RNA component with oxidoreductase activity. AB - A novel RNA component with oxidoreductase activity (diaphorase activity) has been purified from an RNA fraction of Torula yeast. The RNA component was obtained in a 0.05% yield by a series of steps, SDS-phenol extraction, nuclease P1 digestion, alkaline phosphatase digestion, anion exchange chromatography, and HPLC on an ODS column. PMID- 2101916 TI - New reagents and solid support for automated oligonucleotide synthesis. AB - The optimal system for the rapid, efficient, convenient, and economical synthesis and purification of synthetic oligonucleotides has been advancing. By recognizing the very rapid reaction kinetics and taking advantage of an efficient, low volume delivery system, cycle times have decreased to about 5.5 minutes, without compromising synthesis performance. A new set of base protecting groups for cyanoethylphosphoramidite nucleoside monomers have been developed, which decreases the post-synthesis time requirements. A particular form of polystyrene has also been developed as a solid support for automated oligonucleotide synthesis. Typical sequencing or PCR primers (20mers) now require less than 2 hours for synthesis and 2 hours for cleavage and deprotection. PMID- 2101917 TI - Structure and properties of oligonucleotide analogs having phosphoramidate linkages. AB - The oligothymidylate analogs, having several stereo regular phosphoramidate linkages, were synthesized. Melting temperatures(Tm) of complexes of the analogs and poly(dA) were measured by spectroscopic method. The abilities of the analogs to form the complexes with poly(dA) depended on their P-chirality of their modified linkages: one of the chiral isomers formed stable complexes, but another isomer formed less stable complexes. PMID- 2101918 TI - Photocycloaddition of 6-chloro-1,3-dimethyluracil to benzene. PMID- 2101919 TI - Molecular cloning of cDNA coding for rat plasma glutathione peroxidase. AB - The plasma glutathione peroxidase (PGSH-PO), which is different from erythrocyte glutathione peroxidase (EGSH-PO) in immunochemical property and substrate specificity, was purified from male Wistar rat serum. The amino acid sequence of 5 independent peptides were determined and a cDNA clone for this enzyme was isolated from placental cDNA library. The nucleotide sequence of the cDNA revealed that, similar to EGSH-PO cDNA, the seleno-cysteine was genetically encoded by "TGA" codon. On comparing the nucleotide sequences of EGSH-PO and PGSH PO, no significant homology was found in the vicinities of "TGA" codons of both enzymes. PMID- 2101920 TI - Dynamic behavior of large DNA molecules in an aqueous solution toward the understanding of pulsed-field electrophoresis. AB - Conformational dynamics of large DNA molecules have been monitored by use of a fluorescence microscopy. The time-trace of the movement has been quantitatively analyzed with Fourier transformation. PMID- 2101921 TI - Interactions between quadruple-stranded oligodeoxyribonucleotides and drugs. AB - Circular dichroism (CD) and fluorescence spectra have been measured for complexes formed between four-stranded G4-DNA and ethidium bromide (EB). The EB-G4-DNA complexes showed similar induced CD spectra, compared with the induced CD spectrum of the EB-calf thymus DNA complex. PMID- 2101922 TI - The selective binding of HMG1 to the cruciform DNA structure and the subsequent resumption of transcription. AB - The binding of DNA binding protein HMG1 to palindromic sequences that can form the cruciform structure in supercoiled DNA and the subsequent effects on the transcription of the sequence were examined. The results show that the cruciform structure formed under negative supercoiling is a block to transcription and that HMG1, which bound selectively to single-stranded region within the cruciform, can remove the block by altering DNA conformation to allow the stalled RNA polymerase at the block to resume transcription. PMID- 2101923 TI - Oxidation of nucleosides and nucleotides by peroxosulfate ions. AB - Treatment of 5-methylpyrimidine nucleosides and nucleotides with sodium peroxodisulfate in sodium phosphate buffer solution at pH 7.0 at 75 degrees C resulted in the selective oxidation of the methyl group. On the other hand, oxidation of thymidine by potassium peroxomonosulfate gave thymidine glycols. PMID- 2101924 TI - Complexation of nucleotides via electrostatic and hydrogen bonding interactions. PMID- 2101925 TI - Codon usage and secondary structure of mRNA. AB - The specific codon usage pattern of the repetitive unit nucleotide sequence of silk fibroin mRNA suggests that selection has operated on the codon usage to optimize the secondary structure characteristic of the mRNA. The correlation between the stability map of local secondary structure of type I collagen mRNA and the codon usage pattern and the translation rate of the collagen is also implied. PMID- 2101926 TI - Recognition by restriction endodeoxyribonuclease EcoRI of octadeoxyribonucleotides containing modified sugar and base moieties. AB - The modified base and sugar moieties, 8-oxo-7,8-dihydroadenine (HO8A),8 methoxyadenine (MeO8A),8-methoxyguanine (MeO8G) and 9-[(2-hydroxy-1 (hydroxymethyl)-ethoxy)-methyl]-adenine (acA), were chemically introduced in place of the adenine or guanine in the octa-deoxyribonucleotides [d(GGAATTCC)] containing recognition sequence of Eco RI. to the regular DNA-fragment. PMID- 2101927 TI - The interaction of the benzimidazole dye Hoechst 8208 with nucleic acids. AB - The interaction of Hoechst 8208 (H8208) with DNA and synthetic polynucleotides has been studied by absorption, fluorescence, flow dichroism, circular dichroism (CD), and viscosity measurements. The results are compatible with an intercalative mode of H8208 binding. PMID- 2101928 TI - Further evidence for synthesis of screening pigment granules involved in the photosensory membrane turnover of the crayfish photoreceptor. AB - Photosensory membrane degradation in crayfish occurs at first in multi-vesicular bodies (MVBs) and then, with the aid of lysosomal enzymes, in lysosome related lamellar bodies. In organ culture experiments with the isolated crayfish retina (Orconectes limosus) small screening pigment-like granules became visible under the electron microscope in such lamellar bodies and suggested a possible relation of photosensory membrane degradation and screening pigment granule synthesis. Chloroquine, an inhibitor of lysosomal activity, when added to the culture medium reduced the appearance of screening pigment-like granules in lamellar bodies, but led to the appearance of these granules in mature MVB's, indicating the involvement of lysosomal enzymes in the formation of pigmented lamellar bodies. In a second set of experiments the effect of bright light on the screening pigment granule ultrastructure of crayfish phoreceptors was investigated. It was found that after bright light exposure large numbers of little screening pigment granules (0.15-0.3 microns) were located between or close to rhabdomeral microvilli that were not at these sites in crayfish kept under natural light. MVB's were also reduced in size, and among the little screening pigmentary organelles granules of different electron density and morphology appeared. Additionally, vesicle flux to little screening pigment granules was detected. The screening pigment granules of the little type did not seem to be transported close to or between the microvilli, but appeared to be synthesized at these sites within little MVBs. PMID- 2101929 TI - Histopathology of melanocytic lesions in goats and establishment of a melanoma cell line: a potential model for human melanoma. AB - Melanocytic cells from white Angora goats were studied in vivo and in vitro. The histopathology of pigmented areas of skin from the most common sites of melanoma (solar-exposed areas of the ear, face, and perineum) resembled that of the epidermal melanocytes in Hutchinson's melanotic freckle in humans. Seven melanoma biopsies from 6 Angora goats showed histopathological features in common with human melanoma. A melanoma cell line, GM-1, was established in culture from a lymph node metastasis obtained from an animal that had a primary tumor excised and later developed extensive metastatic disease. GM-1 cells were mainly diploid, amelanotic, proliferated rapidly, spontaneously formed vacuolated cells, and were tumorigenic in nude mice. The species of origin of the GM-1 line was confirmed by isozyme profiles. GM-1 cultured cells and the original biopsy both expressed S 100 protein and tyrosinase antigen. Using GM-1 cells as the immunogen, a monoclonal antibody (MoAb 1F1) was derived that reacted strongly with a 116 kDa antigen in 50% of the GM-1 cells, but had little activity with goat fibroblasts (GM-F) or with human melanoma cells. GM-F, on the other hand, yielded more intense staining than GM-1 with an intermediate filament antibody (IFA), reacting with a 58 kDa antigen in both cell lines. The sensitivity of GM-1 to anticancer agents was similar to that of human melanoma cells. The pathology of caprine melanoma and its association with sun-exposed sites in relatively young animals suggest that it may be a suitable model for studying induction of melanoma by natural sunlight. PMID- 2101930 TI - 4-Hydroxyanisole: human pharmacokinetics. AB - The pharmacokinetic behaviour of 4-hydroxyanisole (4HA) has been studied in ten female patients with recurrent malignant melanoma confined to the lower limb. Ten grams of 4HA was infused twice each day via a catheter placed in the common femoral artery for a maximum of 4 days. Blood samples were collected after the first and fourth infusions in all patients and the serum 4HA concentration assayed. Following infusion, the serum 4HA concentration declined in two phases, the half-lives (t1/2) of the distribution and elimination phases being 6.3 and 70.9 min, respectively. The serum 4HA concentrations and area under the curve (AUC) declined significantly between the first and fourth infusions. There was a significant rise in the apparent volume of distribution (VD) of 4HA between these times but no change in the t1/2 of the elimination phase or the clearance rate. It is concluded that there is no evidence that enzyme induction influences the clearance of 4-hydroxyanisole from the bloodstream in the short-term. However, it may be appropriate to adjust dosage regimens to take account of the change in VD that occurs with time. PMID- 2101932 TI - Iris stromal pigment cells of the ringed turtle dove. AB - Irides from adult Ringed Turtle Doves (Streptopelia risoria) were examined using both light and electron microscopy. The anterior surface of the iris stroma contained numerous large venous sinuses overlying bright yellow pigment cells which we classified as "reflecting xanthophores." The pigment cells were filled with irregularly arranged yellow reflecting crystals and occasional pterinosome like structures. The irides were extracted in NaOH and the extracted pigments analyzed using paper chromatography and spectrophotometry. A unique bright orange fluorescent band was found in the iris extract, but the chemical nature of the band was not determined. Although guanine was expected to be a major component of the reflecting "platelets," based on previous work with other Columbiformes, it could not be demonstrated chromatographically or spectrophotometrically. PMID- 2101931 TI - Experimental boron neutron capture therapy for melanoma: systemic delivery of boron to melanotic and amelanotic melanoma. AB - The boron-containing melanin precursor analogue p-boronophenylalanine (BPA) has previously been shown to selectively deliver boron to pigmented murine melanomas when administered in a single intragastric dose. If boron neutron capture therapy is to become a clinically useful method of radiation therapy for human malignant melanoma, the boron carrier must be capable of delivering useful amounts of boron to remote tumor sites (metastases) and to poorly pigmented melanomas. We have now determined the ability of BPA to accumulate in several nonpigmented melanoma models including human melanoma xenografts in nude mice. The absolute amount of boron in the nonpigmented melanomas was about 50% of that observed in the pigmented counterparts but was still selectively concentrated in the tumor relative to normal tissues in amounts sufficient for effective neutron capture therapy. Single intragastric doses of BPA resulted in selective localization of boron in the amelanotic Greene melanoma carried in the anterior chamber of the rabbit eye and in a pigmented murine melanoma growing in the lungs. The ratio of the boron concentration in these tumors to the boron concentration in the immediately adjacent normal tissue was in the range of 3:1 to 4:1. These distribution studies support the proposal that boron neutron capture therapy may be useful as a regional therapy for malignant melanoma. PMID- 2101933 TI - Activation of protein kinase C by myristate and its requirements of Ca2+ and phospholipid. AB - Myristate (C14:0) was found to significantly activate partially purified rat brain Ca(2+)- and phospholipid-dependent protein kinase (PKC). The Ka value, the concentration needed for half maximum activation, for C14:0 in the presence of 1 microM Ca2+ and 20 microM phosphatidylserine (PS) was 20 microM. This activation required Ca2+ and acidic phospholipid and was associated with a decreased Ka for Ca2+ of the enzyme to 10 microM in an analogous fashion as dioleoylglycerol (DO) or phorbol myristate acetate (PMA). The phospholipid requirement for the activation was concentration dependent and was inhibited by 1-(5 isoquinolinesulfonyl)-methylpiperazine dihydrochloride (H-7), a inhibitor of this enzyme. The concentration of H-7 required for half inhibition of the enzyme was about 15 microM and maximum inhibition was about 75%. The concentration profile of cytoplasmic proteins phosphorylated by C14:0-activated PKC was similar to that by PMA-activated PKC. The 47 kDa protein of guinea pig neutrophil was also phosphorylated by the C14:0-activated PKC. It is further discussed whether PKC can function as signal transduction for stimulus-mediated generation of superoxide in neutrophils. PMID- 2101934 TI - Characterization of skeletal muscles by MR imaging and relaxation times. AB - Magnetic resonance (MR) images of three major flight muscles of chicks were obtained with surface coils using a 0.3 Tesla whole body imaging system (FONAR Beta 3000). The two fast muscles, pectoralis major (PM) and posterior latissimus dorsi (PLD), and a slow muscle, anterior latissimus dorsi (ALD), were identified in the axial, coronal, and sagittal images. The signal intensity (SI) of each muscle was electronically measured and its ratio to the background noise (S/N) was determined. Although visually the three muscles showed intermediate SI, the slow and fast muscles could be differentiated on the basis of their S/N values. These values were invariably higher in the slow muscles than in the fast muscles. To understand these differences, the muscles were excised and their mono- and multiexponential MR relaxation times (T1 and T2) were determined at 30 MHz. Multiexponential analysis enhanced the differences between the muscle types. With the sole exception of short T2, all relaxation components of the slow muscles were significantly longer than those of the fast muscles. These results suggest that elevation in the S/N, T1 and T2 values of muscles may not necessarily indicate a pathologic event, but may reflect the preponderance of slow fibers. PMID- 2101935 TI - Long-range effects of direct-hit ultraviolet and particle radiation in oncogene activation. AB - A simple statistical analysis shows that the oncogene-activation effect of chemical carcinogens cannot be explained if one takes into account only short range effects. As one of the most probable solid state physical long-range effects, the generation at the site of carcinogen binding of travelling solitary waves, which can interfere with DNA-blocking protein interactions, is discussed. It has been shown that the direct hit carcinogenic effects on DNA by ultraviolet- or particle radiation can also be explained by the generation of solitary waves (in the latter case the first step is a collective plasma oscillation which decays to individual local excitations and ionizations). PMID- 2101936 TI - NMR monitoring of the anaerobic metabolism of frog muscle at rest. AB - The time dependence of Lactate (Lac), H+, Adenosine-triphosphate (ATP), Phosphocreatine (PCr), Hexose-monophosphate (PME), and Inorganic Phosphate (Pi) levels has been obtained for frog muscle at rest in anaerobic conditions by multinuclear NMR. All information has been collected on the same samples alternatively tuning the probehead on 1H- and 31P-NMR frequencies. ATP, PCr and H+ levels show the same time dependence for all the samples, while PME, Pi and Lac levels vary in time differently from one sample to another. No direct correlation between the Lac appearance and the H+ concentration has been found. PMID- 2101937 TI - [Respiratory function in patients immediately after surgery of the thorax or upper abdomen]. AB - The study deals with the patients in the first postoperative hour following the operation in the upper abdomen or thorax. We considered the respiratory function of the patients in the first postoperative hour and how the respiratory function is influenced by the residua of general anesthesia at that time. Statistically significant decrease of postoperative SaO2 values was found and many patients were hypoxemic after the operation. We found decreased minute ventilation in the first postoperative hour in both groups of patients. Anyway the minute ventilation was more decreased in the abdominal group of patients who recovered from intravenous anesthesia. The conscience as well was more slowly returned to the patients in the abdominal group. In the first 30 minutes more abdominal patients suffered from the muscular weakness following intraoperative relaxation. But this first half an hour after the operation they had satisfactory level of analgesia left. To the contrary the postoperative pain was more severe in the thoracal group of patients. Postoperative gas exchange was more often and more seriously disturbed in the thoracal group of patients who in majority suffered from previous lung disease, which means they had greater ventilation/perfusion imbalance and greater right to left shunt. In the abdominal group only the patients who had relatively short intravenous anesthesia were found hypoxemic in the first postoperative hour. We think that in these patients the gas exchange abnormalities immediately after the operation are also caused by the hypoventilation which often follows general anesthesia. PMID- 2101938 TI - [Pollen asthma]. AB - In a group of 38 patients with typical symptoms of pollen asthma, 34 pollen allergens were used attempting to determine what kinds of pollen most frequently occurred as causative agents leading to senzibilization in patients from the area of Banija. In subsequent procedure, positivity of cutaneous tests was found to correlate with the blood level of specific IgE (RAST), whereby a high percentage of consistent results was observed. Although polysensibilization is an important problem in the etiological diagnosis of this disease, we are inclined to believe the case history data supported by the results of allergometric tests to be quite sufficient to establish a relation between individual pollens and disease symptoms. Thus, allergologic examinations should involve accurate detection of the largest number of causative agents possible to allow both successful prophylaxis and specific immunologic treatment. PMID- 2101939 TI - [Nodular amyloidosis of the lungs associated with Sjogren's syndrome]. AB - Pulmonary amyloidosis can develop together with both primary or secondary amyloidosis, isolated or associated with amyloidosis of other organs. In the study a case of a 59 year old female with multiple nodules and diffuse amyloid infiltration in pulmonary parenchyma associated with Sjorgen's syndrome is presented. Amyloid deposits were also found in the surgically removed parotid salivary gland, mostly in its blood vessel walls. PMID- 2101940 TI - [Hodgkin's lymphoma of the lungs]. AB - A case of the patient with Hodgkin's lung lymphoma, who ten years ago was treated because of having Hodgkin's lymphoma of the mediastinum and neck, is reported in this paper. This time, the patient has been admitted to the hospital due to the pulmonary infiltration in the left upper lobe. As the etiology of the pulmonary infiltration could not be established by a routine diagnostic procedure (sputum cytology, catheter bronchial aspirate smears, bronchial brushing, excision of the bronchial mucosa, transtracheal and transbronchial aspiration), the transthoracic fine needle aspiration was performed to confirm the diagnosis. Cytologically, beside erythrocytes, the cells of the bronchial epithelium, eosinophilic granulocytes and lymphocytes, the cells of the Reed-Sternberg cell type were found in the transthoracic aspirate smears too. PMID- 2101941 TI - [Cytology of bronchial inflammatory pseudotumor]. AB - A presentation is given of a 23-year-old girl who due to cough, hemoptysis and chest pains was treated in the regional hospital as having pneumonia. A bronchoscopy was performed and it revealed the tumor which obturated the right main bronchus. Due to this, surgery was performed. The cytologic analysis of the sample, taken intraoperatively, showed that numerous fibroblasts, single or combined in groups, lymphocytes, plasma cells, mastocytes and some neutrophilic granulocytes were present as well as macrophages. PMID- 2101942 TI - [Sarcoidosis with an unusual clinical course]. AB - Sarcoidosis is a disease which in 90-100% affects the thorax and other organs in 20-50%. Although a systemic disease, its pathohistologic verification concurrently performed in different organs is most interesting. A case of a patient with sarcoidosis and pathohistologic examination of bioptic material revealing sarcoid granuloma in mediastinal glands, liver and parotid gland is reported together with clinically evident eye and central nervous system involvement. PMID- 2101943 TI - [Determination of blood volume in pulmonary capillaries in patients with chronic obstructive lung disease]. AB - The subjects were divided into four groups, three of which consisted of patients with various degrees of lung obstruction, while the fourth was the control group. The patients were divided according to the spirometric values: VC, FEV1, FEV1/VC%. The diffusing capacity was determined on the basis of the single breath method and graphical separation of the diffusion components was performed. It was found that the diffusing lung capacity was slightly lower in patients with mild to severe obstructive lung disease. The capillary blood volume was also slightly lower. Correlations between the degree of obstruction of the respiratory system and the diffusing lung capacity or the lung capillary blood volume was not statistically significant (p greater than 0.5). In studying patients with obstructive lung disease we were unable to establish which of the diffusion components significantly affected the value of the total diffusing lung capacity. PMID- 2101944 TI - [Percutaneous transthoracic aspiration biopsy guided by computer tomography]. AB - CT-guided percutaneous transthoracic aspiration biopsy presenting one of interventional radiologic procedures, has enabled the sample providing for cytologic analysis. It has been frequently used with the aim of confirmation or elimination of malignant neoplastic process. The main advantages of CT over fluoroscopy are precise needle visualization, documentation of needle tip in the lesion, puncture of small, for fluoroscopy unreachable lesions, as well as the adequate presentation of eventual complications. The authors have analysed, retrospectively, 195 findings of patients, who underwent CT-guided Chiba needle percutaneous transthoracic aspiration biopsy. The finding was cytologically representative in 85.64% of cases, unrepresentative in 14.36%. Out of all complications, pneumothorax (9.74%) and perifocal hematom (9.23%) were most frequent. Contraindications, complications and safety of this very useful method in definitive diagnosing and planning of the adequate therapy have been discussed. PMID- 2101945 TI - [Comparison of the results of transthoracic needle biopsy of the lungs using the Nordenstrom and the Rotex needles]. AB - In the diagnostics of nodular and infiltrative lung lesions in 28 patients the transthoracic needle biopsy of the lung was performed both by Nordenstrom and Rotex needle. In confirming the cancer, both needles were equally satisfactory. By Rotex needle the tissue sample was obtained also from hard lesions from which the tissue sample with Nordenstrom needle couldn't be obtained. By transthoracic needle biopsy of the lung the diagnosis of benign disease was confirmed in two patients with isolation of Mycobacterium tuberculosis from the sample obtained by Rotex needle. PMID- 2101946 TI - [Normal values of the diffusing capacity of the lungs in adults]. AB - A steady state diffusing capacity (DLCO) has been measured in 509 healthy (normal) adults (288 males and 221 females) of the age between 18 and 74 years. Obtained DLCO values were related to age, height, body weight and body surface area. Data suggest that there is a good correlation between observed independent variables and DLCO, although there were differences related to sex, presumably because of wide individual variation. Regression equations for predicted values of DLCO were derived. The regression equation based on age in nonsmokers is: Men: DLCO: 28.5705--0.1428 x years + 0.0104 x height in cm; Women: DLCO: 7.4519- 0.0406 x years + 0.1910 x height in cm. The predicted values of DLCO, regardless to smoking, are presented in table form, which can be used in everyday work. PMID- 2101947 TI - [Approach to artificial respiration using differential ventilation in open thoracic surgery]. AB - The purpose of our study was to correct the vertical ventilation perfusion anomaly in lateral position using a differential ventilation with the two identical electronic synchronized "Servo" ventilators, during the thoracotomy. Our study included 44 patients. The differential ventilation has been investigated on the two clinically standardized simplified models. In model 1 distribution of the ventilation volume dependent-independent lung was 50%/50% with a selective PEEP in the dependent lung of 10 cm/H2O. In model 2 distribution of ventilation volume dependent-independent lung of 70%/30% with selective PEEP in the dependent lung of 5 cm H2O. Statistical analysis of our results shows that if we use the differential ventilation model 2 during the thoracotomy we could obtain: a) the lowest values of the shunt in the group of pulmonary patients b) elimination of an appearance of a single critical values of the shunt and a low value of PaO2 in both groups of patients. PMID- 2101948 TI - [Use of Runac in patients with infections of the lower respiratory tract]. AB - Thirty patients went through the outpatient treatment. Causative agent was established in sputum, throat and nose smears of 26 patients. Streptococcus pneumoniae (56%) and Haemophilus influenze (30%) are mostly isolated. Good effects of the medicine is characteristic by quick withdrawal of the symptoms characteristic for respiratory tract infections (cough and expectoration, febrility, physical finding) as well as by debacillosis after 10 days therapy. The effective result of medicine has been particularly noticed through quick reduction until complete disappearance of expectoration after three to four days since the onset of treatment. No side effects of the medicine have been found. PMID- 2101949 TI - [Bronchoscopy in the post-therapeutic monitoring of patients with bronchial carcinoma]. AB - A study of 970 patients treated for bronchogenic carcinoma (operation, cytostatic therapy, irradiation) reveal that only 122 (12.5%) were evaluated by the bronchoscopy. Among 47 (38.5%) out of 122 patients recidivation was confirmed (cytology or histology). The efficacy of radiology and sputum cytology is poor. Only 22/47 (47%) had radiologic evidence of recidivation and 18/47 (38%) had positive sputum cytology. Radiology and sputum cytology reveal recidivation in 27/47 (57%) patients. It means that bronchoscopy is the method of choice in the posttherapeutic monitoring of patients with bronchogenic carcinoma. PMID- 2101950 TI - [Effect of salbutamol administered directly by a nebulizer or by means of a spacer on bronchodilation]. AB - During three successive days in 14 patients with bronchial asthma after application of Salbutamol directly from the metered-dose inhaler (MDI) or indirectly by spacer the changes of FEF and FEV1 were measured. For inhalation through spacer the double blind crossover trial with placebo was used. Out of 12 patients three of them responded with better flows (FEV1, FEF) after inhalation via MDI. In 7 of them there were no significant differences between ways of application while in two of them the flows by spacer were significantly better. Tachypnea, low lung volumes as well as poor co-operation of the patient, especially elderly, should speak in favour of the use of spacer. However, in young, co-operative asthmatic patients the MDI is suitable. Further controlled studies of new applications of inhalation therapy should be studied. PMID- 2101951 TI - [The role of fiberoptic bronchoscopy in the detection of bronchopulmonary carcinoma]. AB - The results of 578 bronchoscopy findings are presented in two periods of time differing in the method of performing the bronchologic procedure. The first period refers to the time from 1977-1979 when the rigid bronchoscope was applied while the second period was from 1980-1982 when the routine method of fiberbronchoscopy was introduced. During 1977-1979 78.6% of the bronchopulmonary carcinoma were verified, while during 1980-1982 the percentage was increased to 81.6%. The relation between verified central and periphery bronchopulmonary carcinoma performed by rigid bronchoscope was 3.5:1, while by fiberbronchoscopy this proportion significantly increased to 1.6:1. This result indicates the dominant role of fiberbronchoscopy in the detection of periphery bronchopulmonary carcinoma. PMID- 2101952 TI - [Pathophysiologic mechanisms of functional disorders of the cardiorespiratory system in snoring]. AB - Disturbances in the function of cardio-respiratory system due to nasal obstruction, accompanied by snoring, are described. Obstructions to other levels, oropharynx, pharynx and larynx, also inducing such disturbances are mentioned, with particular reference to snoring which may lead to the development of apnea during sleep. The need of a multidisciplinary approach to such patients is underlined, with a very specific role of the otorhinolaryngologist, especially when obstruction of the nose has caused such a disturbance. The act of snoring can be eliminated or diminished, and the development of obstructive apnea during sleep prevented or interrupted by accurate indications for and properly performed reconstructive surgery of the nose. PMID- 2101953 TI - [Importance of measurement of systemic oxygen transport and tissue oxygenation in the treatment of acute respiratory insufficiency]. AB - The patients with acute respiratory failure of different etiology are presented. The results of hemodynamic measurements together with those of oxygen transport and tissue oxygenation are given. The results reveal that in hypovolemic shock the transport system of oxygen and tissue oxygenation have been soon normalized by adequate therapy. However, more complicated is the condition of patients with sepsis and adult respiratory distress syndrome (ARDS) with disturbances in microcirculation. In them the oxygen uptake (VO2) is directly dependent upon the oxygen transport (DO2) i.e. much higher values of DO2 should be maintained by therapeutic measures than in conditions with intact microcirculation. According to their own experiences and data from the literature the authors consider that in patients with ARF in whom by the conventional methods the condition cannot be improved an invasive monitoring for following the hemodynamic measurements of oxygen transport and tissue oxygenation should be indicated for successful treatment. PMID- 2101954 TI - [Evaluation of the Vitalomer-1 electronic spirometer]. AB - A new home-made electronic spirometer (Vitalomer 1) is presented. The adequacy of measurement of lung volumes and flows with Vitalomer is assessed in two ways: by registration of volume changes after filling the device by air from the syringe of known volume and by so called "biological testing". By this method in the group of healthy subjects and patients with airflow obstruction the volumes and flows were simultaneously measured both by Vitalomer and standard spirometer (Vitalograph). The values, measured by both devices, were compared according to two statistical methods. Analysis has showed that Vitalomer is comparable in measurement of volumes and flows with well-known Vitalograph and that it fulfils the criteria proposed for spirometers by American Thoracic Society (ATS) and Communaute Europeenne du Charbon et de l'Acier (CECA). The handling with new device is very simple as well as its cleaning. Vitalomer is therefore appropriate for diagnostic spirometry both in out-patients clinics as well as in hospital wards. PMID- 2101955 TI - [Unusual metastatic shadows in the lungs and mediastinum]. AB - A wide spectrum of malignomas may develop calcified or ossified pulmonary changes of different appearance, thin or thick walled air containing cavities, or calcifications in the mediastinal lymph nodes. These unusual radiographical manifestations of metastatic deposits in the lung and mediastinum may be misdiagnosed as benign lesions what is a reason for considerate evaluation of these findings. PMID- 2101956 TI - [Radiographic appearance of fluid in the pleural space]. AB - Observations of the diagnostic procedures of 397 patients treated due to the pleural effusion have been presented. Some of the methods were very differential. Pleural effusions were not only an etiological problem but sometimes the morphological identification is very difficult because of the atypical view of the radiologic appearance. X-ray examinations of the effusion in many projections enables differentiation from other cases. In cases where clinical and X-ray examinations cannot be performed different procedures like transthoracic tap and explorative thoracotomy should be performed. PMID- 2101957 TI - [Personal experience in the treatment of pulmonary tuberculosis in mentally retarded persons]. AB - The results of the therapy of pulmonary tuberculosis in 90 mentally retarded patients in various forms and degrees of retardation are presented. General and clinical condition of 62 patients was very bad prior to the onset of antituberculotic therapy and most of them were immobile due to the mental retardation and dissemination of pulmonary tuberculosis. In 30 patients advanced form of tuberculosis, in 54 patients mild form and in 6 patients a minimal degree of tuberculosis were found. In hospitalized patients all clinical forms of pulmonary tuberculosis were found. The therapy started with triplicate antituberculotic therapy and the patients were also administered other drugs due to their mental retardation. During the first two months of antituberculotic therapy a high mortality rate was registered (27 or 30%) especially in younger patients. The reason for such high rate cannot be attributed only to pulmonary tuberculosis but also to the primary disease as was the main reason of patients' hospitalization at the institute for mentally retarded persons. Many complications in antituberculotic use could not be registered since many of the basic data could not be obtained from mentally retarded subjects. The complete recovery or improvement of pulmonary tuberculosis was achieved in 63 patients. PMID- 2101958 TI - [Modern approach to the classification and diagnosis of pneumonia]. AB - New classification of pneumonia is pragmatic since a significant criterion is a condition in which an infection may develop: inflammations of the lungs in the home environment, immunodeficient patients, hospital infections, as a result of iatrogen complication, epidemics, etc. The principle of etiologic differentiation is reasonable when the therapy is indicated with certainty. Due to the difficulties in isolation and identification of sputum as well as the disappearance of the agent on onset of treatment because of specific therapy, the pathogenetic evolution and morphologic definition of the process is of great importance in the diagnostics and classification of pneumonia. In most patients the pneumonia has a clear course and the diagnosis is mostly established either by epidemiologic and clinical finding, laboratory testing and radiographically or by the response on empiric therapy. In some cases the invasive methods of diagnostics should be applied (BAL, transtracheal biopsy) in order to avoid false positive findings from the upper respiratory tract. PMID- 2101959 TI - A correlational and factor analysis of anticipatory and consummatory measures of sexual behavior in the male rat. AB - This study investigated the relationship among measures of anticipatory and consummatory sexual behavior displayed by male rats in the bilevel chambers designed by Mendelson and Gorzalka (1987). Normative data from a standard test of sexual behavior were gathered from 80 intact, sexually experienced male Long Evans rats and subjected to multiple correlational and factor analyses. The correlational analysis confirmed that several consummatory measures of copulation were related significantly, whereas the anticipatory measure, level changing, was statistically independent of consummatory measures. Factor analysis using orthogonal rotations revealed five factors that accounted for 95% of the intersubject variance for all measures: Copulatory Rate, Initiation, Hit Rate, Mount Count, and Anticipation. These results indicate that at least five conceptual mechanisms are required in any theoretical description of male sexual behavior in the bilevel chamber. In particular, the extraction of separate anticipation and initiation factors indicates that these aspects of male sexual behavior are distinct. The use of bilevel chambers thus may facilitate the identification of potential neurochemical or endocrine mechanisms associated with different aspects of male sexual motivation. In addition, several statistical techniques are discussed with the aim of reducing the elevated experiment-wise error that can occur when related measures of sexual behavior are analyzed independently. PMID- 2101960 TI - The serum glucose response to acute stress is sensitive to the intensity of the stressor and to habituation. AB - The reliability of serum glucose concentrations as an index of habituation to chronic stress was evaluated in adult male rats. The glucose response to immobilization was attenuated by six days of previous chronic exposure to the same stressor, the degree of reduction being related to the duration (15 min, 1 hr or 4 hr) of the daily exposure to immobilization. In another experiment, three groups of rats were exposed to one of three stressors (handling plus change of room, restraint in tubes, or immobilization by wood boards), 1 hr daily for 27 days. On day 28, when faced with the same acute stressor to which they were chronically exposed, the rats showed a consistent reduction in glucose response, regardless of the type of stressor used. In addition, in stress-naive rats serum glucose levels were related to the intensity of the stressor as assessed by three independent measures (food intake, body weight changes, and adrenal weight after chronic exposure to the stressor). These data indicate that, under appropriate conditions, glucose levels can be a good index of both the intensity of acute stress experienced by the rats and their habituation to repeated stress. PMID- 2101961 TI - Plasma corticosterone is increased and correlated with brain acetylcholine in physostigmine- but not in neostigmine-treated rats. AB - Rats were given intraperitoneal injections of physostigmine (PHYSO), neostigmine (NEO) or saline (SAL). Either 15 or 30 min later the number and intensity of observable cholinomimetic effects (OCE) was determined, plasma was collected for corticosterone (Cst) measurement, and the cerebral cortex, striatum, hippocampus and hypothalamus were removed after microwave treatment for the measurement of tissue acetylcholine (ACh) and choline (Ch) concentrations. Plasma Cst correlated with the number of OCEs at both 15 and 30 min in both NEO- and PHYSO-treated animals. Although the number and intensity of OCE were the same in NEO- and PHYSO treated animals 15 min after injection, plasma Cst was significantly higher in the PHYSO-treated group. ACh levels in the cortex were also increased in PHYSO- compared with NEO-treated animals 15 min after injection. Ch levels remained unchanged. Plasma Cst correlated positively with ACh levels in the cortex and striatum in PHYSO-treated rats both 15 and 30 min after injection. These data support the involvement of central cholinergic mechanisms in the regulation of the HPA axis. PMID- 2101962 TI - Influence of clenbuterol, a beta-adrenergic agonist, on desipramine induced growth hormone, prolactin and cortisol stimulation. AB - We report herein the effects of the beta-adrenergic agonist clenbuterol on desipramine (DMI)-induced growth hormone (GH), prolactin (PRL) and cortisol secretion in healthy male subjects. In the first study, nine subjects were treated with either clenbuterol (0.04 mg, p.o.) or placebo. In the second study, 12 subjects received either DMI (50 mg, i.v.) alone or in combination with clenbuterol (0.04 mg, p.o.) given 60 min prior to DMI administration. Clenbuterol alone had no influence on GH, PRL, or cortisol concentrations, compared to placebo. DMI alone caused GH stimulation (mean maximum = 15.7 +/- 3.4 ng/ml), which was significantly lower after combined administration of DMI and clenbuterol (mean maximum = 7.7 +/- 1.6 ng/ml) (p less than or equal to 0.01). DMI-induced PRL and cortisol stimulation was not influenced by clenbuterol pretreatment. These results indicate the inhibiting influence of noradrenergic beta-receptors on GH stimulation. PMID- 2101963 TI - Congenital adrenal hyperplasia. I: Gender-related behavior and attitudes in female patients and sisters. AB - Thirty-five female patients with congenital adrenal hyperplasia (CAH) were compared to a group of 16 healthy sisters in regard to gender-related behavioral patterns, present attitudes, and plans for the future. A semi-structured interview with the subjects, ages 11 to 41 yr, and their mothers concentrated on four to five age stages. Results of retrospective data from single items as well as from several related composite scales ("interests and behavior," "appearance," "overall scores") revealed significant group differences: Both in mother assessment and self-assessment, CAH patients showed a "more masculine" orientation than their sisters, but this was far from consistent across all age stages, especially for single items. Unexpectedly, the gender-behavior differences between CAH patients and sisters did not hold for certain items and scales of "social behavior" (e.g., assertiveness, dominance, acceptance in peer groups) and, in contrast to some of the existing literature, also not for "high energy expenditure." With regard to expectations for the future, CAH patients had less of a "wish to have their own children" and a higher preference for "having a career versus staying at home." Age, socioeconomic status, intelligence, and presence or absence of a sister as possibly intervening psychosocial/demographic factors could not explain the group differences in behavior. Degree of genital masculinization (Prader stages) or "onset and quality" of therapy as measures of pre- and postnatal androgenization, respectively, could also not account for the degree of the "more masculine" orientation in the CAH group. Nevertheless, the overall results are compatible with earlier findings on the masculinizing effects of prenatal androgens on behavior in humans and point to a time period after sexual differentiation of the genitalia and before birth as the most likely one for the effects of prenatal hormones on behavioral masculinization in humans. PMID- 2101964 TI - Congenital adrenal hyperplasia. II: Gender-related behavior and attitudes in female salt-wasting and simple-virilizing patients. AB - The salt-wasting (SW) and simple-virilizing (SV) forms of congenital adrenal hyperplasia (CAH) are characterized by distinct prenatal hormonal milieus. To test whether these hormonal milieus differentially influence the development of a "more masculine" behavioral pattern in female CAH patients (Dittmann et al., 1990), SW patients (N = 13) were compared both to SV patients (N = 20) and healthy sisters of both groups (N = 16). The data are based on semi-structured interviews in which subjects (11-41 yr) and mothers were asked about aspects of "Gender-related interests and behavior," "Level of activity," "Social behavior," (reflecting e.g., assertiveness, dominance, and acceptance by peer groups) and "Appearance"; these areas of interest were represented by composite scales. On most scales, and by both mother-assessment and self-assessment, SW patients differed significantly from both SV patients and sisters in having a "more masculine" orientation. SW patients also showed a higher "Level of activity." These SW group results probably account for much of the CAH/sister differences reported in the companion article (Dittmann et al., 1990). In contrast, SV patients differed from the sister sample on only a few scales. There were no significant differences between SV and SW subjects in the degree of virilization of the external genitalia (indicating no group difference in prenatal androgenization). SW patients were treated "earlier" and "better" after birth (indicating less postnatal androgenization). However, these medical conditions, as well as several psychosocial/demographic variables, could not explain the group behavioral differences. These results do not support a primarily psychosocial explanation of behavioral development in CAH patients, especially those with the SW condition; they rather suggest differential organizational effects of two different hormonal environments (SV vs. SW) during critical periods of prenatal CNS development. PMID- 2101965 TI - Psychoneuroendocrinological and immunological parameters in cancer patients: involvement of stress and depression. AB - Plasma noradrenaline (NA), adrenaline (A), dopamine (DA), platelet serotonin (pS), free serotonin (fS), cortisol (CRT), growth hormone (GH), peripheral blood lymphocytes (lymph), lymphocyte subpopulations (LSS) and CD4/CD8 ratio were serially assessed in 50 non-medicated, advanced cancer patients (spontaneous evolution) and in age- and sex-paired controls. Clonidine tests and psychiatric evaluations were also serially performed. Patients showing long symptomless periods had all normal values except for raised pS, whereas those who remained free of symptoms for only a short time had raised NA, A and CRT, plus lowered pS values. Further increases in NA, A and CRT, plus additional increases in DA and fS, occurred during exacerbation periods, during which times reductions in lymph, LSS and NK also were observed. Patients in terminal stages showed maximal decreases of all neurotransmitters and immunological parameters; only DA and fS remained raised. Psychiatric interviews performed simultaneously with the clonidine tests revealed a low incidence of moderate depression during symptomless periods and no depression during exacerbation periods. Several significant positive and negative correlations between neurotransmitters and immunological parameters were found during exacerbation periods. Pain, although not intense, and other symptoms required occasional administration of low doses of non-opiate analgesics. PMID- 2101967 TI - [Modified cystotomy in course of time--case report of operation method Partsch I]. PMID- 2101966 TI - Luteinizing hormone and cortisol responses to naloxone in normal weight women with bulimia. AB - The present study was undertaken in order to establish whether alterations in the endogenous opioid control of luteinizing hormone (LH) and ACTH/cortisol secretion occur in bulimic women with normal body weight and normal menstrual cycles. For this purpose, the capability of the opioid antagonist naloxone (4 mg injected as an intravenous bolus at time 0, plus 10 mg infused over 2 hr) to increase the circulating levels of LH and cortisol was tested in nine bulimic women and in nine age- and weight-matched normal controls. All women were tested on the 22nd day of a normal menstrual cycle. Two days later, a control test with normal saline (NaCl 0.9%) instead of naloxone was performed. The basal levels of LH and cortisol were similar in the bulimic and normal subjects and were not modified by the administration of normal saline. In contrast, the administration of naloxone significantly increased plasma LH and cortisol levels in all subjects, with peak LH responses at 30 min and peak cortisol responses at 60 min. The naloxone induced LH and cortisol increases were significantly higher in the bulimic women than in the normal controls. These data indicate the presence of an increased opioid inhibitory tone in the control of LH and ACTH/cortisol secretion in normal weight bulimic women with normal menstrual cycles. PMID- 2101968 TI - [Clinical trials of silanized adhesive bridges with two distinct preparation concepts]. PMID- 2101969 TI - [Quality judgement of curets of various manufacturers with respect to their durability]. PMID- 2101970 TI - [Endoscopic and traditional methods of caries diagnosis--procedure report (2)]. PMID- 2101971 TI - [Interpretation of radiographs]. PMID- 2101972 TI - [ABC of practice management. H-human capital]. PMID- 2101973 TI - [Allergic reactions of mouth mucosa in denture wearers--case report]. PMID- 2101974 TI - [Intravenous access--usual or exception?]. PMID- 2101975 TI - [Local anesthetic effects on the gingiva of two mucosal preparations]. PMID- 2101976 TI - [Repair of porcelain shells]. PMID- 2101977 TI - [Utilization of Branemark implants for orthodontic anchorage--case report]. PMID- 2101978 TI - [Dentin wound dressing and its practical application (3)]. PMID- 2101979 TI - [Prosthetic rehabilitation of a dysgnathic patient--case report]. PMID- 2101980 TI - [Conservative correction of anterior diastema as well as a deep bite--case report]. PMID- 2101981 TI - [Plaque prevention with amine fluoride/tin fluoride]. PMID- 2101982 TI - [Yashica Dental Eye II--report of experience]. PMID- 2101983 TI - [Interpretation of radiographs]. PMID- 2101984 TI - [ABC of practice management. I--Identification]. PMID- 2101986 TI - [Damage to dental instruments (1)]. PMID- 2101985 TI - [Intravenous access--usual or exception? (2)]. PMID- 2101987 TI - [Clinical testing of alloys (1)]. PMID- 2101988 TI - [Osseointegrated implants in treatment of patients with missing teeth- preliminary study of 876 implants]. PMID- 2101989 TI - [Cervical proximal polishing of amalgam restorations]. PMID- 2101990 TI - [Titanium supraconstruction on endosseous implants]. PMID- 2101991 TI - [Use of hand skeleton radiographic analysis in orthodontic diagnosis]. PMID- 2101992 TI - [Diagnosis and differential diagnosis of oral hyperpigmentation]. PMID- 2101993 TI - [Interpretation of radiographs]. PMID- 2101994 TI - [ABC of practice management: J--annual planning]. PMID- 2101995 TI - ["Reconstruction with osseointegrated implants with the ITI-System (Bonefit)." One week course of Prof. N.P. Lang, Bern]. PMID- 2101996 TI - [Informed consent in anesthesia]. PMID- 2101997 TI - [Damage to dental instruments (2)]. PMID- 2101998 TI - [Clinical testing of alloys (2)]. PMID- 2101999 TI - [Scanning electron microscopical and light microscopical investigations of apical closure quality in usual practice transfixation systems]. PMID- 2102000 TI - [Dentin wound dressing and its practical application (1)]. PMID- 2102001 TI - [Simulation of esthetics of veneers without tooth preparation directly in patients' mouth]. PMID- 2102002 TI - [Temporary care of small anterior spaces]. PMID- 2102003 TI - [Molar distalization with intraoral molar distalization curve--method for controlled position of 6-year molars in Class I relation (2)]. PMID- 2102004 TI - [Model for start of oral hygiene education]. PMID- 2102006 TI - [Interpretation of radiographs]. PMID- 2102005 TI - [Endoscopic and traditional methods of caries diagnosis--procedure report (1)]. PMID- 2102007 TI - [Histological aspect of cyanoacrylate dental cavity lining]. PMID- 2102008 TI - [Characteristic oral changes in patients with anorexia nervosa and bulimia nervosa]. PMID- 2102009 TI - [Modern amalgams-polishing and corrosion prevention in in-vitro study. 3. Results and discussion]. PMID- 2102010 TI - [Haemophilus influenzae type B: subtyping of strains isolated from respiratory infections using the outer membrane protein profiles]. AB - Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) applied to outer membrane protein (OMP), extracted by a micromethod, was employed to subtype H. influenza b type I. A total of 37 H. influenzae b strains were isolated from children under 4 years of age, either with lower acute respiratory infection (LARI), or asymptomatic carriers matched according sex, socioeconomic level and seasonality. Twenty seven out of the 37 H. influenzae b strains belonged to biotype I. On the basis of OMP profiles, these 27 were classified into 8 subtypes (Figs. 2, 3, 4 and 5). The probability of two randomly chosen isolates having different OMP profiles was 0.733. The subtype termed "a" showed the greatest relative frequency and was detected both in invasive strains and in those isolated from throat samples of LARI cases and healthy children. The use of 14% SDS-PAGE allowed de detection either of a 51kD or a 49kD, as well as 25-40kD proteins, in a single run (Fig. 1). Most subtype profiles showed the 51 kD protein. Growth conditions and extraction of OMPs by our modified micromethod provide a single and inexpensive procedure within the means of the average clinical laboratory. Besides, this test is much less time-consuming than classical assays. Jointly, biotyping , serotyping and OMP profile determination, proved a useful epidemiological tool to survey H. influenzae b infection. PMID- 2102011 TI - Microbiology of diarrhoea in young beef and dairy calves in Argentina. AB - Rotavirus, Cryptosporidium sp, and Salmonella spp. were investigated in the faeces of 452 diarrhoeic calves from 36 beef and 33 dairy herds. Animals surveyed were from a few days of age up to approximately 1 month of life. Enterotoxigenic Escherichia coli (ETEC) was studied in 212 calves, aged 15 days or less. The animals were from the Provinces of Buenos Aires (59% of the calves), Cordoba (18%), Santa Fe (16%), Entre Rios (5%) and La Pampa (2%). A minimum of 4 calves were sampled on each farm. In beef calves rotavirus was excreted by 45.1% of the animals. Cryptosporidium by 30.5% and Salmonella serovars Arechabaleta, Livingstone, Panama and Typhimurium by 1.9%. In dairy calves Cryptosporidium was excreted by 29.6%, rotavirus by 23% and Salmonella serovar Dublin by 1.6%, ETEC was not detected in any calf. Rotavirus was the most widespread agent, detected in 32 (88.9%) beef herds and excreted by more than 50% of the calves in half of these herds. In contrast, rotavirus was only detected in 19 (57.5%) dairy herds and was excreted by more than 50% of the calves in 6 of these herds. Crytosporidium oocysts were identified in 27 (75%) beef and in 23 (69.7%) dairy farms. Salmonellosis due to serovar Dublin was associated with diarrhoea in 2 dairy herds. Concurrent infection with two or three agents occurred in 36 (8%) calves and 38 (55.1%) farms; the combination rotavirus-Cryptosporidium was found in 32 (6.9%) calves an in 33 (47.8) farms. PMID- 2102012 TI - Thermophilic Streptomyces found in sugarcane environments in Jujuy, Argentina. AB - The thermophilic Streptomyces strains isolated from: a) airborne dust of bagasse storing area, b) dry sugarcane residues and c) stored sugar manufacture wastes are described. The strains grown at maximal rates at 50 degrees C have a gray shade after 48 h. All the mature spores retain the malachite green stain. They were identified with Williams' clusters: S. chromofuscus, S. cyaneus, S. microflavus, S. antibioticus, S. halstedii and S. violaceusniger. The last three clusters coincide with the species found by other workers in bagasse. PMID- 2102014 TI - [Complete nitrification in soil columns perfused with nitrite]. AB - Four columns of the same soil were put under the continuous flow of a NaNO2 solution [50 ppm N], so as to follow the evolution of nitrification. The soil, the columns as well as the solution continuous flow regulating system, were prepared as in the previous experiments. The columns, with the exception of No1 (control), contained also the following substances: No2 and 4: 2% de CaCO3 and No3 and 4:0.0015% SO - 4-S. Since the eight day of perfusion all the effluents had an important concentration of nitrate (Figure 1), exceeding in them, the sum of [No-2-N] an [NO-3-N] (Table 1) the concentration of th NO-2-N of the perfusion solution. Finally, the [NO-2-N] was reduced importantly in the effluents, and the (NO-3N), in all of them, stabilized itself as values nearing 50 ppm. Its suggested that at the beginning of the experiment, an endogenous source of NO-2 was functioning, which could explain the observed phenomenon, and that later it ceased to do so. The populational density of NO-2 oxidizers increased, during the experiment, 49 times (Table 2). An increase was also measured in the populational density of NH+4 oxidizers, which amounted to 41 times. This later fact contributes to support the existence of an endogenous provision of NO-2 during the initial part of the experiment. PMID- 2102013 TI - [1st isolation of strains of Staphylococcus aureus producing toxic shock syndrome toxin 1 in food handlers in Argentina]. AB - Thirty nine milk handlers from a factory of dairy products in the Province of Buenos Aires were examined for their nasal carriage of S. aureus strains capable of producing toxic-shock-syndrome toxin-1 (TSST-1). In addition, chance samples of handled foods, crude milk and milky fermented derivates (MFD) were studied. Strain isolation was made on Mannitol Salt Agar and on Baird-Parker Agar. Typical colonies were identified by their biochemical properties. Cultures that were found to be S. aureus were selected for analysis of the TSST-1 production. Eight milk handlers (20.5%) were carriers of S. aureus strains. Seven isolates (87.5%) were classified as biotype A (human ecovar) and 1(12.5%) was classified as biotype B (swine and poultry ecovar). Three out of 8 S. aureus biotype A isolates (37.5%), produced TSST-1. Taking into account the number of milk food handlers sampled (39), the carried rate of toxigenic strains was 7.6%. Three S. aureus strains were isolated from crude milk; 1(33.3%) was classified as biotype B and 2(66.6%) as biotype C (cattle and sheep ecovar). Thirteen S. aureus strains were isolated from MDF; 5(38.0%) were classified as biotype A, 1(7.7%) as belonging to biotype B and 7(53.8%) as belonging to biotype C. None of them had the ability to produce TSST-1. PMID- 2102015 TI - [Loquat canker: a new disease for Argentina]. AB - A stem canker disease caused by Pseudomonas syringae pv. eriobotryae (Takimoto) Young, Dye y Wilkie on loquat (Eriobotrya Japonica [Thumb] Lindl) was recorded for the first time in Argentina. Symptoms of the disease appeared as dry stem cankers which in advanced stages surrounded the stems. Similar cankers were noticeable on leaves midribs. Seven bacterial strains were isolated from diseased loquats and their identification was based on disease symptoms, pathogenicity and cultural and biochemical characteristics. All strains were levan positive and gave a hypersensitive reaction on tobacco leaves. Neither arginine dehydrolase nor oxidase was detected in any of the strains which produced a diffusible green pigment on King B which fluoresced under UV light and a distinct diffusible brown pigment on King B, SPA and Tween 80 media within 5-7 days of incubation. Lipolysis of Tween 80 was also recorded. The symptoms observed in the field and obtained by experimental inoculations were similar to those induced by Pseudomonas syringae pv. eriobotryae in the original description of the disease. PMID- 2102016 TI - [Adjuvants: update on concepts]. PMID- 2102017 TI - Vaccines in health strategies of developing countries. The role of biotechnology and social sciences. Workshop held in Bergen, Norway, December 7-9, 1989. Proceedings. PMID- 2102018 TI - An anthropological perspective on the acceptability of immunization services. AB - This review first discusses the relevance of anthropology for Primary Health Care generally and specifically with respect to the acceptability of immunization, and summarizes some of the factors which have been found to be associated with acceptability. It then focuses on the collaboration between anthropologists and bio-medical scientists and on the deployment of anthropological methods for discovering the specific reasons for low acceptability for disparate groups. The review concludes with a cautionary note on the use of social marketing for increasing acceptability. PMID- 2102019 TI - A short review of biotechnological methods of relevance to modern vaccine development. AB - The development of new methods and techniques in biotechnology over the last two decades has opened the way for fresh strategies to develop new and better vaccines. The relevant techniques have been developed through important discoveries in immunology, gene technology and polymer chemistry. The purpose of this short review is to discuss these techniques in the light of vaccine development, without going into details regarding each specific disease and vaccine. PMID- 2102020 TI - Development of oral vaccines against cholera and enterotoxinogenic Escherichia coli diarrhea. AB - An oral cholera vaccine consisting of the immunogenic but completely nontoxic B subunit of cholera toxin in combination with heat- and formalin-killed cholera vibrios has been developed. This vaccine, which was designed to evoke antitoxic as well as antibacterial intestinal immunity, has in extensive clinical trials including a large field trial been shown to confer, without any side-effects, protection against cholera lasting for at least 3 years. The vaccine also induced protection of shorter duration against diarrhea caused by enterotoxinogenic Escherichia coli (ETEC). Significant progress has also been made recently using recombinant DNA techniques towards development of a live attenuated oral cholera vaccine. Furthermore, new knowledge about virulence factors and protective antigens of ETEC has given promise that an effective oral ETEC vaccine may soon be developed combining a B subunit toxoid with inactivated ETEC expressing the most important colonization fimbrial antigens. PMID- 2102021 TI - Prospects of vaccination against schistosomiasis. AB - The development of a vaccine against schistosomiasis is necessary in order to reduce the risk of reinfection after drug treatment. Recent reports converge on a message strongly supporting the existence of naturally acquired human immunity to this infection and reinforcing the hypothesis that at least partial protection can be achieved by artificial means. Advances in molecular biology have led to the identification and characterization of an array of protective schistosome antigens, and the introduction of new sophisticated methods for their production enables a bypass of previous low-yielding and labour-intensive procedures. Although vaccination of animals with these antigens does not result in consistent levels of protection exceeding 50%, the reproducible induction of about 80% protection with live attenuated cercariae indicates that immunization against schistosomiasis is achievable. The finding of antibodies capable of blocking protective immunological responses suggests a complicated interaction between different properties of the immune system which needs to be understood and modulated in the direction of improved resistance. An overview of the present status of vaccine development in schistosomiasis including results in different animal models and evidence from field studies on humans is presented and discussed. PMID- 2102022 TI - Vaccinations in the health strategies of developing countries. AB - The initiative established by the World Health Organization in 1974 under the title of the Expanded Programme on Immunization (EPI) has resulted in immunization programmes being strengthened in developing countries so that they now cover 66% of children reaching their first birthday with a dose of DPT or polio vaccines. Immunization programmes are currently preventing over 2 million deaths among children in developing countries from measles, neonatal tetanus and whooping cough. Future challenges for the EPI include: raising and sustaining immunization coverage; controlling the target diseases, with specific focus on the control of measles, the elimination of neonatal tetanus and the eradication of poliomyelitis; introducing new or improved vaccines; promoting other primary health care practices; and research and development. Immunization will become an increasing priority for developing and industrialized countries alike as an increasing array of vaccines become available for public health use. Further research to simplify and reduce the costs of vaccine production and administration and to better understand the factors contributing to the acceptability of immunization services is needed as a complement to research to develop additional vaccines. PMID- 2102023 TI - Development of vaccines against leishmaniasis. AB - A vaccine against leishmaniasis is the only practical means to control this disease in many epidemiological situations. Two approaches have been adopted: pragmatic and systematic. The pragmatic approach involves trial of crude leishmanial components in animals and then in humans if they meet safety requirements. The systematic approach requires identification of the protective immunogen(s), appropriate carrier and adjuvant, and determination of the immune responses and modes of presentation of the immunogens to achieve the desired effect. Progress have been made with both approaches. Killed Leishmania promastigotes have been used in Brazil for high risk individuals with encouraging results. Impressive results have also been observed with killed Leishmania plus BCG for immunotherapy of cutaneous leishmaniasis in Venezuela. With the systematic approach, recent research has identified some protective immunogens, cloned protective murine T-cells, developed primate models resembling the human disease, cloned and expressed genes of some potential immunogens, identified some features of the protective immune response, determined modes of presentation of immunogen to produce a protective response, and been able to protect mice (even/Balb/c) against L. major infection. The difficult part that remains is the implementation of a vaccine or any control measure in the poor communities where they are needed and where the lack of required infrastructure does not allow adequate coverage. PMID- 2102024 TI - [Cancer chemotherapy today and in the future]. AB - The results which are obtained by means of the chemotherapy of cancer during a forty-year history lie behind our expectations. Nevertheless the chemotherapy of cancer is to be used curatively in about 15 per cent of all sorts of tumours, and a palliative effect can be expected in about 40% of all tumorous diseases. It must also not be forgotten that the chemotherapy of cancer has stimulated the oncologic basic research as well as the clinical oncology and is continuing to stimulate it. There are furthering and promising conceptions for the future development of chemotherapy of cancer which are based on the rapid increase of knowledge on the part of the oncologic basic research. There is no doubt that the advance of the oncologic basic research can be introduced into clinical practice only on the way of chemotherapy of cancer. In all other conceptions of the chemotherapy of cancer the patient's right to a high quality of life must not be forgotten. Here a change of thinking with regard to the positions of the past is necessary. PMID- 2102025 TI - [The theory of microcirculation. 4: The movement of molecules through semipermeable membranes]. AB - The movement of the molecules through semipermeable membranes does not only follow thermodynamical principles but it is also in keeping with the classical mechanics of particle movement. Hence, in presence of chemical potentials a simple diffusion at semipermeable membranes is impossible because of additional convective fluid transport, which influences the process. Reversely, every solution passing through semipermeable membranes generates a certain pattern of chemical gradients. These findings are important for the calculation of protein distributions in tissues. The current view of application of thermodynamics on microcirculation includes several misinterpretations concerning the movement of molecules through semipermeable membranes, because it does not take into consideration the special preconditions. The present paper shows, that it is necessary to reinterpretate the current concept of this field of the microcirculation. PMID- 2102026 TI - [Gradual evaluation of repolarization disorders with ECG mapping]. AB - 143 test persons, (31 healthy persons, 30 borderline cases and 82 patients with chronic coronary heart disease) were examined at rest and on submaximal exertion by means of a mapping ECG (72 electrodes) and their findings were valuated depending upon the severity of the chronic coronary heart disease. The significance of the individual mapping ECG parameters in gradually valuating the disturbances of repolarisation was stated by correlation to the severity of the chronic heart disease and decreased in following order: 1. relative surfaces, 2. total surface with ST decrease in mV, 3. maximum decrease of ST, 4.4. sum of the decrease of ST in mV, 5. sum of negative area integrals of ST and 6. the minimum quotient of increase. The extension of a myocardial ischaemia could be stated with the total area by means of decreases of ST and its maximum by means of the maximal decrease of ST. The severity of the coronary heart disease could be gradually estimated with the "relative surfaces" of the mapping ECG at rest in mild to moderate degrees of severity and under submaximal exertion in all degrees of severity of the coronary heart disease. In a gradual evaluation of the mapping ECG the extension, the intensity, localisation and kind of the disturbance of the myocardium must be considered with regard to the dipole behaviour and to the potential decrease of the cardioelectric field as well as to the degree of severity of the disease. PMID- 2102028 TI - [Participation by the established physician in clinical drug trials]. AB - After performance of the phases I to III of the drug test which is carried out in clinics and special institutions into the phase IV, the ambulatory test, mainly the physician with own practice is included. This test is performed either as a controlled study with clearly outlined test aim and methodology or as open study in which physician and patient known which medicaments are used. Before the physician participates in a clinical study he should for himself carry out a preliminary test. Thereby he should carefully consider the proportionality of the necessity of the testing against possible dangers for the individual and also the feasibility of the test in his practice with its patients. An important prerequisite is the presence of a test plan, whereby the information and the consent of the patients or test person is decisive for the permissibility of the test. The producer of the test preparation takes the total responsibility for the clinical test including the liability. PMID- 2102027 TI - [Ruptured myocardial infarcts]. AB - Forty one cardiac rupture complicating acute myocardial infarction (AMI) were studied in a ten-year period. The anterior AMIs are most likely to be observed with ruptures. The interval from the onset of AMI to the clinical detection of rupture was short (acute period). Some factors such as physical work in the acute period and transmural infarctions strongly infiltrated with leukocytes cause a higher frequency of rupture. Diabetes and hypertension might be predisposing factors. PMID- 2102029 TI - [Effectiveness and tolerance of long-term uricosuric treatment]. AB - In an open-controlled, randomized trial over 24 weeks, the serum uric acid lowering effect of a daily dose of 100 mg allopurinol in combination with 20 mg benzbromarone compared to 300 mg allopurinol only was investigated on a total of 60 patients suffering from hyperuricemia. Both preparations led to a decrease of the serum uric acid value to normal. In those patients however, who had received the combination the reduction of the serum uric acid level was more pronounced. Tolerance was generally good. Side-effects were not reported. PMID- 2102030 TI - [Quality and value of expert assessment of disability with reference to evaluation of cardiovascular diseases]. AB - Because of the high frequency of diseases of heart and circulation a great number of physicians is concerned with experts opinions of them. There were 273 experts opinions from the rural and city district of Leipzig analysed in order to estimate quality and assertions force of experts opinions of invalidity with regard to estimation of diseases of heart and circulation. There was often found that data of anamnesis and documents extracts did not satisfy. But the parts about findings and estimates of experts opinions were in most cases well. Often complaints of patients and possibilities of therapy and rehabilitation were considered too less. The code of diagnosis did not always correspond to the International Statistical Classification of Diseases and Death Causes. There was often no sufficient evidence of diagnosis and degree of heaviness in the text of the experts opinions. But clinical findings with function checks were very well documented in many experts opinions. PMID- 2102031 TI - [Effect of sports on the distribution of body fat]. AB - The pathogenetic effectiveness of the risk factor overweight is essentially modified by the distribution of the fatty depot. The form of obesity, the primary obesity, which above all is to be found in men is connected with a relatively high risk for the appearance and progression of several chronic diseases which at present determine morbidity. An only two-hour sports activity per week has a great influence on the size and the distribution of the lipopexia. Sporting persons have less body fat than inactive ones. In particular in sporting males the deposition of fat in the abdominal region is much limited. PMID- 2102032 TI - [Changes in serum uric acid concentration after defined physical stress]. AB - The influence of two variants of strength training on serum level of uric acid was examined in four weightlifters. In a pilot study a remarkable increase was found in both after maximum strength orientated squats and after power-related strength training. The results were discussed in terms of different kinds of recruitment of motor units, the time structure of examined movements and the arthritis urica as a typical disturbance of the purine nucleotid metabolism. PMID- 2102033 TI - [Mini-mapping ECG]. AB - 63 patients with clearly defined myocardial infarction and an echocardiographically evident akinesia and hypokinesia, respectively, were examined by means of the echocardiography, the conventional ECG (12 leads) and the classical mapping ECG (69 leads). From the latter a mini-mapping ECG (12 chest electrodes) was led. IN 20% of the cases we did not find an accordance between the classical mapping ECG and the mini-mapping ECG in the localization of an echocardiographically proved disturbance of the excursion of the heart wall. In these cases small circumscribed myocardial lesions were concerned which were located particularly postero-inferiorly, the proof of which restricted itself to a thoracic surface less than 54-108 cm2 in the classical mapping ECG. But in larger lesions of the myocardium already the conventional ECG shows correct diagnostic statements. The coordination of the myocardial infarctions to the individual parts of the heart can be performed on the basis of a topographic mapping ECG card. A quantitative estimation of the electrocardiographic findings is not possible with the mini-mapping-ECG. The diagnostic valency of the mini mapping-ECG is to be arranged only in the third place after the classical mapping ECG and the conventional ECG! PMID- 2102034 TI - [Classification of rheumatic diseases. Knowledge and problems]. AB - A classification of diseases serves following purposes: --Collection and processing of data on morbidity and mortality (administrative objective) --Tool for diagnostic evaluation (clinical decision making) --Indicator of the scientific state of the art of the disease (theoretic taxonomy). In the efforts to unify the classification of rheumatic disease, following two goals are realistic: 1) Improvement in the effective communication 2) Agreement with the targets set. The International Classification of Diseases for Rheumatology and Orthopedics (ICD-R and O), which has been jointly elaborated by the International League Against Rheumatism (ILAR) and the Societe Internationale de Chirurgie Orthopedique et de Traumatologie (SICOT), is a practicable international standard for the next years. PMID- 2102035 TI - [Obstructive jaundice caused by Ascaris lumbricoides]. AB - In middle Europe biliary complications caused by Ascaris lumbricoides are very rare. We report on endoscopic removal of an Ascaris out of the common bile duct in a 81-years-old woman. PMID- 2102036 TI - [The physician as an accident witness: emergency care and problems of failure to provide first aid]. AB - As a witness of an accident the physician has always the duty to render first aid. At least he has to examine carefully whether his help is not or no more necessary. On account of his professional abilities the duty to first aid may concern him as the only person also among several participants, and he must always care to take the best possible measures for the prevention of dangers. In the other case he exposes himself the danger of culpability for not having performed first aid. Apart from a penal verdict also the possibility of a verdict by a professional court of justice for the same offence can be added. In the process before the professional court of justice is examined, whether or not the physician failed in his professional duty to protect and restore health as well as to reduce complaints (section 1, number 2 MBO). PMID- 2102037 TI - [Group practice: partners should agree on property division with the divorcing party and determine legal inheritance rights]. PMID- 2102038 TI - [Local anesthesia--10-year observation in a dental practice]. PMID- 2102039 TI - [Fossa articularis changes using Herbst appliance after mandibular advancement]. PMID- 2102040 TI - [Cancers: concerns and early diagnosis by the dentist]. PMID- 2102041 TI - [Clinical aspects and therapy of myxofibromas]. PMID- 2102042 TI - [Position of EDP in dental practice]. PMID- 2102043 TI - [Dental care concerns--necessary or desirable?]. PMID- 2102044 TI - [Rare odontogenic tumors of the jaw bone]. PMID- 2102045 TI - [Hairy cell leukemia and its oral accompanying complications--case report]. PMID- 2102046 TI - [Interdisciplinary cooperation in adult treatment from orthodontic viewpoint]. PMID- 2102047 TI - [Conservative therapy for maxillary sinusitis. Results after 4 years of oral antral closure]. PMID- 2102048 TI - [Knowledge of caries etiology is crucial]. PMID- 2102049 TI - [Prevention in orthodontics for small child]. PMID- 2102050 TI - [Screw implants of aluminum oxide]. PMID- 2102051 TI - [Present status of porcelain technique]. PMID- 2102052 TI - [Medial subsemilunar cortical depression. Radiographic pseudoforamen of ascending mandibular ramus?]. PMID- 2102053 TI - [Epidemiology and etiopathogenesis of oral carcinoma: current aspects]. AB - This work reviews all the data actually known about the epidemiology and the etiopathogenesis of the oral cancer. Based on an exhaustive literature review, this paper analyses the epidemiological and etiopathogenic factors of the oral cancer. PMID- 2102054 TI - [Differential indications for the surgical management of fractures of the mandibular condyle]. AB - The frequency and importance of collum mandibulae fractures is indicated, especially in connection with the sequels of conservative-functional therapy, and the different classifications and types of fractures are described. The non surgical approach is evaluated as a treatment. Its inconvenient and sometimes unsatisfactory results necessitate the surgical treatment of certain types of collum mandibulae fractures. Absolute en relative indications for osteosynthetic treatment of condylar fractures are noted, the proposed surgical technique is discussed. The importance of a universal preauricular incision continued in an incision for parotidectomy and resulting in a standard incision or a combined preauricular-submandibular incision, is pointed out. Surgical technique for intra and extra capsular collum fractures is illustrated. Our preference goes to functional stable osteosynthesis using titanium mini-plates and the often obligatory dissection of the facial nerve. The so called "condylar shave" or remodelling condylotomy in analogy with the DAUTREY-operation is a therapeutic contingency in case of bilateral collum mandibulae fractures with unilateral low condylar fracture where classical mini-plate osteosynthesis is done, and intracapsular multi-fractured condylar head on the other side where the condylar shave or rubble clearing is performed The attitude towards children is discussed. The result of this surgical technique is illustrated through the follow-up of 73 surgical treatments of collum fractures in 59 patients. We conclude that surgical osteosynthetic treatment of collum mandibulae fractures with a strict indication in case of dislocated and luxated fractures should be included in the therapeutic range of modern maxillo-facial traumatology. PMID- 2102055 TI - Four-step mandibular lengthening to correct a bird face deformity. A case report. AB - A technique for extreme lengthening of the mandible is presented. In one operation it combines several procedures already known, modifying some of them. Its advantage is that the movement is subdivided in 4 steps. Thereby the need for grafting is reduced or even absent and the amount of relapse is probably less important than if fewer but bigger movements were applied. PMID- 2102056 TI - [Classification of bony facial asymmetries]. PMID- 2102057 TI - Benign cementoblastoma: review of the literature and report of a case at an unusual location. AB - Benign cementoblastoma is a rare odontogenic tumour localized in the jaws of young people. Benign cementoblastoma has characteristic radiologic and microscopic features and it appears to be fused to the tooth roots. The most important differential diagnosis is-with a benign osteoblastoma. The tumor should be enucleated and the teeth extracted. This case represents only the third reported case of a benign cementoblastoma associated with a third molar. PMID- 2102058 TI - The Health Care Quality Improvement Act of 1986: its history, provisions, applications and implications. AB - Congress granted qualified immunity from liability for peer review participation to physicians, osteopaths and dentists, created a national practitioner data bank to track inept, incompetent or unprofessional physicians, and enacted procedural rules for due process, privilege restrictions, and reporting and disbursement of information. The Health Care Quality Improvement Act of 1986 is now in full force, and peer review participants are anxious to cloak themselves with immunity from actions brought by health care professionals. Although its goals are worthy, HCQIA's effects remain to be seen. Serious loopholes appear to exist, warranting close monitoring and possibly early amendment of the Act. Cautious judicial assessment is needed, in order to prevent not only circumvention of the Act's requirements by artful litigants, but also use of the national data bank by health care entities as a pretext for denying privileges and escaping antitrust liability. PMID- 2102059 TI - An economic and antitrust analysis of the distribution of medical products. AB - The techniques used to distribute medical products are designed to maximize the manufacturers' profits by charging a relatively low price to hospitals and a relatively high price to other purchasers, such as doctors and nursing homes. This pricing scheme raises complex antitrust problems, including vertical price fixing between the manufacturer and its distributors, price discrimination by the manufacturer, and agreements between the manufacturer and the hospitals restricting the hospitals' ability to resell. This Article examines these antitrust issues. PMID- 2102060 TI - The Uniform Status of Children of Assisted Conception Act: does it protect the best interests of the child in a surrogate arrangement? AB - Medical technology is easing the plight of many infertile couples by offering such reproductive alternatives as in vitro fertilization, artificial insemination and surrogacy. In response to the changes in our society's definition of family, wrought by scientific advances, the National Conference of Commissioners on Uniform States Laws promulgated the Uniform Status of Children of Assisted Conception Act. The purpose of this Act is to protect the interests of children born through extraordinary medical procedures. This Note analyzes the Act's provisions regarding surrogacy and focuses on how the Commission's regulatory scheme fails to protect the child's interests. The Act's alternative of voiding the surrogacy contract also does not protect the child's interests. A more complete regulatory scheme which protects the adult parties' interests, as well as the child's, should be devised, as the adequacy of the adult parties' protection ultimately affects the child's well-being. PMID- 2102061 TI - Conflict in the parameters defining life and death in Missouri statutes. AB - Over the last twenty years, state legislatures have enacted statutes incorporating medically and legally established criteria to be utilized in the determination of death. Similarly consistent criteria for determining the onset of life have yet to be established. As a result, unacceptably conflicting statutory language defining life and the state's interest in that life exists. This conflict can be resolved by a functional approach that consistently applies criteria used to define the end of life to the beginning of life. PMID- 2102062 TI - The cytomorphologic and cytometric manifestations of cervical reparative processes. AB - The process of tissue repair or regeneration is the attempt of the injured tissue to be restructured and to reestablish its function as it existed prior to injury. The cytologic alterations depend on the original tissue site, the elapsed time after the incurred injury as well as on the type of the injury itself. From a practical standpoint, the importance of the recognition of tissue repair alterations as such, is the avoidance of false positive cytologic diagnoses and/or the under evaluation of existing malignant lesions with potentially severe clinical consequences. The computerized on-line file of patients examined cytologically and histologically since the year 1959 which contains over two million patient records was searched for those cases identified as "tissue repair". The major criteria of cytomorphology of tissue repair and differential diagnoses are described. For the purpose of enhancing the differential diagnostic accuracy two procedures useful as diagnostic aids are presented: (1) local administration of estrogens, and (2) computerized cell image analyses evaluated and guided by an artificial intelligence expert system. PMID- 2102063 TI - [Computerized evaluation of reparative processes of the cervix uteri]. AB - This study was aimed to evaluate the effect of polydeoxyribonucleotide (PDRN), as reported in relevant literature, on cervical epithelia dynamics. Particularly, the interactions taking place between columnar epithelium and the squamous one have been examined. For the purposes of the study, the following computerized techniques, already widely known, have been used: The colposcope is joined to a videocamera connected with a computer (AT compatible). The computer is equipped with a graphic card capable to record and to digit the image, i.e. to make it recognizable by the computer itself. Thereafter, many operations can be performed on the colposcopic images: reductions, enlargements, retouches, record, recall, analysis, etc. Moreover, irregular epithelial areas can be easily determined to a good approximation and, using pre-established enlargement ratios, their evolution can be evaluated. By means of this technique 12 out-patients with uterine cervix ectopias, with or without normal transformation zone (NTZ), have been examined. The monthly therapy was 12 pessaries, each containing 5 mg polydeoxyribonucleotide (POLIDES 5--Farmigea), from the 7th to the 18th day of the cycle, repeated for 3 months. Since the first month of treatment a reduction of the ectopic columnar epithelium has been noted in most patients (9 on 12), with a squamous epithelium increase (peripheral reparative process). This process has kept on increasing during the following months in the 9 patients responding to the treatment, whose ectopic areas were covered by squamous epithelium (average 55% of the area; range 33%-78%). No response to the treatment has been shown in 3 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102064 TI - The pharmacologic therapy of post-cauterization and post-laser vaporization with polydeoxyribonucleotide. AB - The most widely used ablative techniques in the therapy of benign cervical lesions are physical treatments with cauterization or laser vaporization; these are, however, usually used for the largest or symptomatic lesions. Many Authors suggest, after physical treatment, the use of topical chemotherapy in order to abolish any possible inflammatory reaction. The use of drugs such as polydeoxyribonucleotide (PDRN) 5 mg (POLIDES 5--Farmigea), provided with reepithelialization and anticomplement action, seems to promote a quicker recovery of the cauterized or vaporized zone, avoiding, at the same time, the secondary inflammatory reaction. The Authors have assessed the quality of reepithelialization by means of PDRN 5 mg ovules of the cervical zone which has been previously subjected to laser vaporization or cauterization for benign cervical lesions or CIN I. The trial was performed with two groups of patients: Group A: laser vaporization, 45 patients, 23 of whom treated with PDRN and 22 with placebo. Group B: cauterization, 46 patients, 24 treated with PDRN and 22 with placebo. The treatment with PDRN 5 mg ovules started on the day of physical treatment and continued for twelve days. The examination of the patients, performed before the treatment (TO) included the following tests: bacteriological test; PAP-smear, colposcopic examination with eventual direct biopsy. The first follow-up (T 1) was performed after 14 days and included a Pap-smear, colposcopic examination and microcolpohysteroscopy (MC) carried out in the zone where physical treatment had been performed, in order to obtain a map of the reepithelialization process process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102065 TI - [Clinico-morphological changes in ectropion after treatment with polydeoxyribonucleotide (PDRN)]. AB - Thirty patients in fertile age affected by ectropion were treated with Polydeoxyribonucleotide (PDRN) (*) vaginal suppositories for 24 days. No other local or general therapy was allowed. The following parameters were evaluated: local symptomatology, tolerability and compliance, vaginal cytology, colposcopic examination, bioptic sampling of affected area prior to and after treatment, and local immune response. The results show the efficacy of PDRN. In fact, after the treatment: reduction of subjective symptomatology with decrease of average score for each symptom; excellent or good tolerability and acceptability; reduced inflammation; increased iodine-dark areas; reestablishment of normal balance in T and B-lymphocytic populations have been found. PMID- 2102066 TI - [Advantages of topical therapy with polydeoxyribonucleotide in reparative processes after cauterization: experience at a center for early diagnosis of genital neoplasms]. AB - This paper evaluates the common practice of a topic medical treatment following cautery (or other kinds of microsurgery) of the uterine cervix. Firstly, a controlled clinical trial on 116 patients treated with kanamycin sulphate alternated to polydeoxyribonucleotide vaginal suppositories, and 124 controls has been conducted. Subjective parameters (leukorrhea, bloody discharge, odorous discharge, more than three weeks vaginal discharge, itching, pain, burning) and colposcopy (Schiller test reactivity, squamo-columnar junction location, abnormal transformation zones, vascular striae, deepithelialized areas or frail epithelium) appeared more favorable in the treated group, the colposcopic finding of phlogosis being the only unfavorable finding more frequent among the treated patients. Successively, a controlled double blind clinical trial with kanamycin sulphate alternated to placebo vs PDRN at different dosages has shown an increase in number of epithelial cells in the treated patients and a better stimulation of fibroblasts by higher dosages of active substance. These results show the efficacy of the studied post cautery treatment schedule, and of PDRN in particular. PMID- 2102067 TI - A non-hormonal therapeutic alternative in cervico-vaginal dystrophies. AB - The pharmaco therapeutic effect of polydeoxyribonucleotide vaginal suppositories in two dosages (PDRN 1,65 mg and PDRN 5 mg)* on vaginal dystrophy was studied. 40 women, aged more than forty, in surgical or physiological climacteric with cervico-vaginal dystrophy were examined. The study was carried out according to the double-blind method, randomized, between groups. Both treatments produced important ameliorations of subjective symptomatology and objective signs. No significant difference emerged between the two preparations. PDRN was proved to be a valid alternative to local hormonal therapies. PMID- 2102068 TI - Anatomical variations of the abducent nerve in humans. AB - Anatomical variation of the nervus abducens in human encephali were found and described. They consisted of (1) an unusual trifurcation of the abducent nerve, limited to the extradural portion of the neural trunk (1.4% of the cases) and (2) the duplicity (11.1%) of the neural trunk, starting before reaching the orbit and ending before reaching the m. rectus lateralis. The possibility of correlating these variations with clinical aspects and forensic interpretations is mentioned. PMID- 2102069 TI - [An atrial hematopoietic locus in the heart of the cave salamander (urodele amphibian)]. AB - Lungless Salamanders of the family Plethodontidae have a reduced interatrial septum. The pulmonary vein is lacking. In these species, the septum as a membranous thin sheet attaches near the dorsal lip of the sino-atrial valve where a connective and muscular column, supporting the valve, extends its branches over the upper wall of the undivided atrial cavity where a sponge-like structure is formed. The meshes of this structure are the site of a erythropoietic activity as shown in the plates. Early stages in active reproduction are found in the external acid layer while in the basic inner layer the red cells undergo differentiation. This locus may be correlated to the particular anatomy of the heart concerning the lacking of the pulmonary vein, the position of the sino arterial aperture shifted to the left side and the reduced interatrial septum. In the large upper cavity of the atrium a certain degree of blood stagnation could be possible which could allow the settlement of this locus. No ventricular erythropoiesis nor epicardial granulopoiesis have been found. This hemopoietic locus is lacking in the family Salamandridae and Anura. PMID- 2102070 TI - Morphology, origin and functions of the thrombocytes of Elasmobranchs. AB - Thrombocytes of Torpedo marmorata Risso and Scyliorhynus stellaris L. (Elasmobranchs) are multiform from rounded to spindle-shaped. They originate in the spleen from prothrombocytes. They appear to be functionally correspondent to mammalian platelets because they form aggregates and adhere to glass and contain the same surface-connected canalicular system (SCCS) as in platelets, as proved by tannic acid treatment. Immunocytochemical staining have demonstrated, moreover, the presence in their cytoplasm of three platelet factors: platelet factor 4, beta-thromboglobulin and factor VIII related antigen. Stimulating agent, like collagen, ADP, noradrenaline, 5-hydroxytriptamine and thrombin induce aggregation of thrombocytes and the empting of their granules and vesicles containing very likely the platelet factors. The above observations leave few doubts on the functional equivalence of elasmobranch thrombocytes to mammalian platelets. PMID- 2102071 TI - Early and transient osteopetrosis in microphthalmic MIB-rats. AB - Microphtalmic blanc mutation (mib/mib) displays a very mild form of osteopetrosis in rats. The autosomal recessive mib mutation shows pleiotropic expressions in homozygotes. Microphtalmia, absence of eye and skin pigmentation, retardation in the tooth eruption were observed in the mutants. Most bone abnormalities occurred in newborns. An increased radiological opacity of long bones, persistence of primitive bone in medullary cavities, reduced number of poorly differentiated osteoclasts in mandibulae, reduced number of mononuclear peritoneal cells as well as reduced number of mononuclear osteoclast precursors in peritoneal cell population were found. In 3 weeks old and in adult mutants, both bone structure and the number of mandible osteoclasts appear normal, but the number of blood monocytes, peritoneal cells and mononuclear osteoclast precursors in peritoneal cell population remain significantly lower than in the healthy littermates. These observations indicate that the early failure of osteoclast differentiation and maturation is transient in the mib/mib form of osteopetrosis. PMID- 2102072 TI - Allometry of hepatic weight growth in human staged fetuses. AB - The growth of the hepatic weight was correlated to fetal parameters of maturity (gestational age, crown-rump length and weight) in 70 human fetuses ranging from 14 to 39 weeks post-conception using the allometric method. The growth of the hepatic weight presents moderate positive allometry relative to age and C-R length, and isometry relative to fetal weight. The coefficiens of correlation are very high (p less than 0.001, Table 1). This study presents growth curves of the hepatic weight useful in medical branches such as anatomy, forensic medicine, fetopathology, medical imagery, onstetrics and pediatrics. PMID- 2102073 TI - Fibre size in the left and right recurrent laryngeal nerves (RLNs) in the man. AB - Some morphological data of the right and left human RLNs were evaluated with the aim of verifying possible differences in the fibre composition of the two nerves. The following parameters were evaluated in the right and left RLNs of five human cases: 1) the maximum diameter of the fibres; 2) the axon diameter and area; 3) the myelin sheath area obtained substracting the axon area from the total area of each fibre. The obtained data were plotted on histograms for each case: moreover, histograms of all fibres of both left and right nerves of all five cases were made. The results show that the values of the maximum diameter of the fibres and of the myelin sheath area are always greater in a statistically significant way in the left RLNs than in the right RLNs. On the other hand the axon diameter is nearly the same in the nerves of both sides. These data suggest that the greater calibre of the myelin sheath in the fibres of the left inferior laryngeal nerve can be responsible of the faster conduction speed in this nerve. This fact might explain the simultaneous arrival of the impulses to the laryngeal muscles of the two sides in spite to the different length of the two nerves. PMID- 2102074 TI - Retinyl palmitate labeled intestinally derived lipoproteins accumulate in the circulation of WHHL rabbits. AB - The behavior of native retinyl palmitate labeled intestinally derived lipoproteins and their remnants was studied in 8 NZW and 8 WHHL (5 homo- and 3 heterozygote) normal-fed rabbits and in 3 cholesterol-fed NZW, after 1 month of cholesterol feeding, and 3 and 5 months after resuming normal feeding. Palmitate labeled lipoproteins were produced by the intestine after administration of 50,000 IU of Vitamin A, together with olive oil via gastric intubation. Blood was drawn before and 3,6,9,12,24, and in some instances, 48 h later. Retinol (R) and retinyl palmitate (RP) were measured in whole serum and in the chylomicron, d less than 1006, d greater than 1006 less than 1019, d greater than 1019 less than 1063, d greater than 1063 less than 1210 g/ml lipoprotein fractions and in the infranatant. The R content of the serum was almost all concentrated in the infranatant, it did not change during the vitamin A test and was similar in WHHL, and normal- or cholesterol-fed NZW rabbits. In the normal-fed NZW the RP content of the serum increased within 6 h after giving the vitamin A fat meal (peak value less than 200 microgram/100 ml) and then decreased. In the WHHL homozygotes, the RP increased to a much greater degree (peak value 600-1820 micrograms) and for a much longer time, as it was still increased in the 5 cases studied after 24 h, and in 3 cases studied after 48 h. Similar RP curves were obtained in NZW rabbits, after 1 month of cholesterol feeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102075 TI - Monocyte activation by smooth muscle cell-derived matrices. AB - Mononuclear phagocytes adhere to and penetrate the vessel wall endothelium and contact the subendothelial space prior to the development of the atherosclerotic plaque. In an attempt to model the early events of plaque development we used an elastin-rich, multicomponent, cell-derived matrix from neonatal rat aortic smooth muscle cells as a substratum for monocytes. Using this model, we show that human monocyte morphology and metabolism are markedly altered by the matrix substratum. When a mixed mononuclear cell population is seeded on matrix or plastic, only monocytes adhere to the matrix surface. In contrast, lymphocytes as well as monocytes adhere to the plastic surface. The matrix-adherent monocytes develop large intracellular granules and form extensive clusters of individual cells. Metabolically, these cells develop sodium fluoride resistant non-specific esterase activity and their media contain more growth factor activity and PGE2. Although total protein synthesis is equivalent in both cultures, the matrix contact induces an increase in specific proteins in the media. We also show that a purified alpha-elastin substratum induces some, but not all, of the monocyte changes seen when using the matrix substratum. Using the alpha-elastin substratum, there is selective adhesion of monocytes and increased growth factor activity, however, the cells are morphologically different from the matrix adherent cells. Thus, the use of the smooth muscle cell-derived matrix, in conjunction with purified matrix components, serves as a model that can provide insight into the mechanisms of monocyte adhesion and stimulation by the matrix environment that exists in vivo. Such mechanisms may be particularly important in atherogenesis. PMID- 2102076 TI - Increased degradation of low density lipoproteins by mononuclear leukocytes associated with coronary artery disease. AB - Low density lipoprotein (LDL) and peripheral blood mononuclear leukocytes (MNL) were isolated from patients with (n = 11) and without (n = 11) angiographically documented coronary artery disease (CAD). LDL degradation rates in MNL were determined in vitro using both autologous and homologous LDL. The mean rate of LDL degradation was 1.7-fold higher in CAD-MNL than in control-MNL (P less than 0.05), independent of the LDL source. The increased LDL degradation rate in CAD MNL appeared to be due to an increased receptor-mediated LDL degradation rate in CAD-MNL and not to an increased CAD-LDL interaction with the receptor since LDL isolated from patients with and without CAD had similar in vitro degradation rates in HL-60 cells and 1.25-dihydroxyvitamin D3-induced HL-60 macrophages. An increased ratio of apo B to cholesterol, specifically apo B to cholesteryl ester, was observed in LDL isolated from patients with CAD. LDL particles isolated from CAD patients contained 14.8% less cholesteryl ester than LDL from control subjects (P less than 0.01). The data suggest that CAD patients have an increased plasma LDL particle number even though they have similar plasma LDL-cholesterol levels as compared to control subjects. These data indicate that CAD patients with normal plasma LDL cholesterol levels have two metabolic abnormalities: an altered LDL composition resulting in particles with reduced cholesteryl ester content and an increased LDL catabolism resulting in an increased influx of LDL cholesterol into MNL; both of which may play a role in the development of coronary heart disease. PMID- 2102077 TI - Changes in the composition of plasma lipoproteins in the chronic uremic rat. AB - The effect of chronic renal failure on the lipid and apolipoprotein concentrations of plasma, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) was studied in an experimental uremic rat model. Control rats were sham-operated and were divided into adlibitum-fed and pair-fed groups. The rats were studied (after an overnight fast) 32 days after the onset of uremia. The uremic rats had a 4-fold increase in plasma urea nitrogen and creatinine. The pair-fed and ad-lib-fed controls had similar levels of plasma urea nitrogen and lipid profiles. In the uremic rats, plasma triglyceride (TG) levels were increased 3.8-fold due to increased TG in the VLDL, IDL and HDL fractions. Their 2-3-fold increase in plasma free cholesterol (FC), esterified cholesterol (EC) and phospholipids (PL) were due to FC, EC and PL increases in VLDL, IDL, LDL and HDL. Their increase in plasma apo B (x 2.4) and apo E (x 1.5) were due to increases in VLDL, IDL and LDL. Their plasma apo A-I increased 2.4 fold due to increases in the LDL and HDL fractions. Uremic rats also had increases in the FC/PL molar ratio in VLDL, IDL and LDL. In their LDL, the apo B/total cholesterol (TC), apo B/PL and apo B/apo E molar ratios were decreased. In their HDL, the apo E/TC and apo E/PL molar ratios were decreased and the apo A-I/apo E molar ratio was increased. In conclusion, chronic uremia causes both quantitative changes in the levels and qualitative changes in the composition of the plasma lipoprotein particles. These results are compatible with the decreased hepatic lipase activities and impairment of remnant clearance observed in human chronic renal failure. PMID- 2102078 TI - Relation of risk factors for cardiovascular disease to early atherosclerosis detected by ultrasonography in middle-aged normotensive hypercholesterolemic men. PCV Metra Group. AB - The relations between carotid arteries and/or abdominal aortic plaque and cardiovascular risk factors were investigated by ultrasonography in 161 untreated hypercholesterolemic normotensive men. Of them, 58 had no plaque (NP group), 34 had carotid but not aortic plaque (CP group), 34 had aortic but not carotid plaque (AP group) and 35 had both carotid and aortic plaques (CAP group). Groups significantly differed for age, smoking, blood pressure, and the ratio of total to HDL cholesterol. Age was higher in CAP group than in NP and CP groups and in AP and CP groups than in NP group. Life long smoking dose was higher in CAP group than in CP, AP, and NP groups. Systolic and diastolic pressures were higher in CAP group than in NP group, systolic pressure was higher in CAP group than in CP group, and diastolic pressure was higher in AP group than in CP and NP groups. The ratio of total to HDL cholesterol was higher in CAP group than in AP, CP, and NP groups. Multiple regression analysis showed that carotid plaque was only related to age, while aortic plaque and the number of sites affected by plaque were correlated to age, smoking and diastolic pressure. These findings suggest that in hypercholesterolemia risk factors other than lipids seem to influence arterial plaque and that risk profile differs according to the plaque location. PMID- 2102079 TI - Aortic endothelial cell damage induced by beta-VLDL and macrophages in vitro. AB - We performed an in vitro study to assess damage to swine aortic endothelial cells by rabbit beta-VLDL and/or rabbit peritoneal macrophages. Incubation of cultured aortic endothelial cells with beta-VLDL, macrophages, or macrophage lysate induced endothelial cell damage time- and dose-dependently as estimated by [3H]adenine release. Incubation of endothelial cells with both beta-VLDL and macrophages produced a synergistic effect on the increase of [3H]adenine release. Pretreatment of the endothelial cells with some kinds of antioxidants (probucol 50 micrograms/ml, vitamin E 50 microM, superoxide dismutase-polyethylene glycol 0.5 mg/ml, or catalase-polyethylene glycol 0.5-1.0 mg/ml) significantly prevented the endothelial damage by beta-VLDL or macrophage lysate. We conclude that beta VLDL and/or macrophages could induce endothelial cell damage and that some kinds of antioxidants could prevent it. PMID- 2102080 TI - Fibrinogen, factor VII clotting activity and coronary artery disease severity. AB - To asses the relationship between fibrinogen, factor VII coagulant (VIIc) activity and extent of coronary artery disease, we studied 43 white males shown to have greater than 50% stenosis of at least one major coronary artery. Thirty six had a definite history of myocardial infarction at least 3 months earlier and were classified as having 1, 2 or 3 vessel disease while 7 had 2 or 3 vessel disease, but no prior infarction. Groups were similar with regard to age, body mass index and blood pressure. In those with documented prior infarction, there was a significant relationship between the extent of atheroma and coagulation variables factor VIIc and fibrinogen. However, given a similar degree of atheroma, patients with prior infarction had significantly higher levels of factor VIIc activity compared with patients without such a history. These results corroborate those from prospective studies confirming a significant role for the coagulation system in the clinical manifestation of coronary artery disease. PMID- 2102081 TI - Analysis of cholesterol ester accumulation in macrophages by the use of digital imaging fluorescence microscopy. AB - Low density lipoprotein (LDL) induced accumulation of cholesterol esters was analyzed by the digital imaging fluorescence microscopy (DIFM) in murine tumor macrophages. To analyze cholesterol ester accumulation, P388D1 macrophages were incubated with increasing quantities of unmodified or acetylated human LDL, washed, and live stained with a lipophylic fluorescent dye Nile Red. The increase in fluorescence intensity was quantitatively determined by the interactive laser cytometer (ACAS 470) and compared with the accumulation of cellular cholesterol esters determined by the gas liquid chromatography. Correlation between the two methods was highly significant (r greater than 0.9, P less than 0.001). A good agreement between the two methods was also found in terms of sensitivity and reproducibility. With the use of 589 nm narrowband interference filter in the light path of emitted light the intensity of fluorescence correlated well with cellular cholesterol ester content even in the presence of relatively high concentrations of triglycerides. Therefore, digital imaging fluorescence microscopy appears to be a reliable method for quantification of cholesterol ester accumulation at the single cell level offering new possibilities of studying interactions between cells and cholesterol ester rich lipoproteins. PMID- 2102082 TI - Hormonal influences on the relationships between body fatness, body fat distribution, lipids, lipoproteins, glucose and blood pressure in French working women. AB - The independent associations between overall obesity, body fat distribution, lipids, lipoproteins, glucose, blood pressure and some hormonal factors (sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG) and fasting insulin) were cross-sectionally examined in 205 French working women. After adjustment for age, overall adiposity assessed by body mass index (BMI) was significantly associated with most metabolic parameters, whereas regional adiposity assessed by the waist-hip ratio (WHR) was significantly associated only with triglyceride, systolic and diastolic blood pressure. Blood pressure, glucose but not triglyceride, were also negatively and significantly correlated with SHBG and positively with fasting insulin. Negative independent associations were found between SHBG and both BMI and WHR, whereas CBG was positively associated only with WHR. Fasting insulin was no longer related to WHR after adjustment for BMI. After controlling for the effect of SHBG or insulin, the associations between triglyceride, blood pressure and both BMI and WHR were not substantially modified. After adjustment for BMI and WHR, fasting insulin was independently associated with both HDL cholesterol and diastolic blood pressure. In conclusion, in these French women, hormonal factors under study appeared to have little influence on the relationships between body fatness, body fat distribution, metabolic variables and blood pressure. PMID- 2102083 TI - Postprandial lipemia, fenofibrate and coronary artery disease. AB - This report describes the response of patients with severe coronary artery disease to a dynamic fat load test and monitors the change induced by fenofibrate therapy. The presence of disease was associated with prolonged and exaggerated hypertriglyceridemia following the meal and with lower basal HDL cholesterol and HDL subfraction masses. A further indicator of risk was the persistence of increased amounts of retinyl palmitate in the plasma of severely affected individuals 24 h after its ingestion with the meal. These observations are consistent with the proposal that the clearance of chylomicrons and their remnants is impaired in coronary atherosclerosis. Fenofibrate reduced alimentary lipemia following the fat load in both normo- and hypercholesterolemic subjects. This was associated with a 10% rise in plasma HDL cholesterol levels. The improvement in chylomicron catabolism probably derived from a 37% increase (P less than 0.001) in lipoprotein lipase activity induced by fenofibrate. Hepatic lipase on the other had was only slightly affected by treatment. PMID- 2102084 TI - Body fat distribution in men with angiographically confirmed coronary artery disease. AB - Body fat distribution and its relationship to coronary artery disease and established cardiovascular risk factors have been studied in a cohort of 286 men aged between 30 and 74 years undergoing coronary angiography. 207 (72.4%) patients showed stenosis (greater than 30%) or occlusion of one or more coronary arteries. whereas the remaining 79 (27.6%) men were free of coronary lesions and served as a control group. 112 men with angiographically defined coronary artery disease had an additional history of myocardial infarction. Body fat distribution was assessed by determining the waist-to-hip circumference ratio. A stepwise logistic regression analysis revealed that in addition to LDL-cholesterol (P = 0.0001) and age (P = 0.0005) an abdominal type of body fat distribution (P = 0.0129) is also a significant risk indicator for the occurrence of coronary artery disease (CAD) independent of body weight and other factors such as total cholesterol, HDL-cholesterol, triglycerides, insulin, systolic and diastolic blood pressure. The results of this study suggest that an abdominal type of fat distribution is associated with an increased risk of coronary artery disease. PMID- 2102085 TI - Effects of simvastatin, bezafibrate and gemfibrozil on the quantity and composition of plasma lipoproteins. AB - Simvastatin, 10-40 mg/d (n = 11), bezafibrate, 600 mg/d (n = 6), and gemfibrozil, 1200 mg/d (n = 5) were administered for 12 weeks after a 4-week placebo period to subjects with initial plasma levels (mg/100 ml. mean +/- SD) of cholesterol (346 +/- 77), and of triglycerides (180 +/- 54). Total LDL-C plasma concentration was lowered 32% by simvastatin and 35% by bezafibrate, but only bezafibrate diminished the triglyceride (41%) and increased HDL-C plasma levels (35%). Plasma lipoprotein fractions obtained by discontinuous gradient ultracentrifugation, namely, VLDL, lighter LDL (LDL-1), heavier LDL (LDL-2) and bulk HDL were chemically analyzed. Simvastatin and bezafibrate significantly diminished the quantity of VLDL and LDL-1 particles, although barely modifying their composition. Neither drug influenced the LDL-2 plasma concentration. Bezafibrate increased the total plasma HDL level little interfering with its chemical composition. Gemfibrozil was the least effective of all drugs but decreased the lipid and protein contents and their ratios in VLDL and LDL-2. PMID- 2102087 TI - Localization of apolipoprotein E in normal and atherosclerotic human aorta. AB - To elucidate the role of apolipoprotein E (apo E) in atherogenesis, we have investigated the localization of apo E in normal and atherosclerotic aortas as well as in other tissues of 32 post-mortem individuals. Using double immunofluorescence it has been found that normal intima of individuals older than 20 years and some adolescents contained immunoreactive material that reacted with poly- and monoclonal antibodies to apo E. A staining pattern of apo E differed from that of apolipoprotein B, the latter being seen in normal intima of each child older than 7 years. Apo E was present extracellularly in lipid streaks and atheromatous plaques, where its staining was particularly intensive around the necrotic zone of plaques. Some macrophages in the plaques of 4 aortas exhibited apo E-positive staining, while aortic endothelial and smooth muscle cells never contained apo E. Apo E-positive staining was not found in the majority of vessel cells, it was always, however, observed in other types of cells including hepatocytes. Kupffer cells, spleen macrophages and cerebral astrocytes. Our findings indicate that only some macrophages in human aorta may be responsible for the production of apo E that can participate in reverse cholesterol transport. At the same time, apo E accumulation in the aortic wall may promote the development of atherosclerosis. PMID- 2102086 TI - Temporal and spatial changes in macromolecular uptake in rat thoracic aorta and relation to [3H]thymidine uptake. AB - Leaky endothelial junctions associated with cell turnover have been suggested to be a hydrophilic pathway for the transport of macromolecules across the vascular endothelium. To demonstrate focal increases in endothelial permeability, the occurrence of localized uptake of macromolecules in the rat thoracic aorta was studied at various time periods after intravascular administration of Evans blue albumin (EBA) complexes. With fluorescence microscopy, EBA uptake in the rat thoracic aorta was visible either as discrete spots or as larger areas in both en face and cross-sectional preparations. The average size of EBA leaky spots increased with dye circulation time, indicating that there is a continuous influx of macromolecules through the transiently leaky junctions in these foci with subsequent diffusion in the vessel wall. There was heterogeneity in EBA spot size distribution, suggesting that endothelial cells undergoing turnover in different phases of the cell cycle might exhibit different extents of junctional leakage to macromolecules. The technique of [3H]thymidine labeling autoradiography was applied to en face preparations of the rat thoracic aorta for identifying replicating endothelial cells. The correlation of EBA leakage with [3H]thymidine labeled endothelial cells was determined. Only 26% of endothelial cells with nuclear incorporation of [3H]thymidine were shown to be associated with EBA leaky foci. This lack of correlation suggests that alterations in endothelial junctional permeability accompanying cell turnover might occur only in some limited time periods of the cell cycle, e.g., the mitotic (M) phase, rather than the whole period of [3H]thymidine labeling. PMID- 2102088 TI - The endothelin peptides ET-1, ET-2, ET-3 and sarafotoxin S6b are co-mitogenic with platelet-derived growth factor for vascular smooth muscle cells. AB - We have investigated whether any of the three isoforms of endothelin (ET) ET-1, ET-2 and ET-3 or the structurally similar peptide sarafotoxin S6b is mitogenic on its own for rat vascular smooth muscle cells in culture. DNA synthesis was determined by a peroxidase-linked double antibody technique to detect bromodeoxyuridine incorporation into the nucleus and stained nuclei were counted by image analysis. None of the ET peptides or sarafotoxin S6b (up to 100 nM) was capable of initiating DNA synthesis in the absence of platelet derived growth factor (PDGF) or fetal calf serum. All the peptides potentiated the mitogenic effect of low concentrations of PDGF. ET-1 and ET-2 (10 nM) caused a 2-fold increase in the number of stained nuclei induced by 5 nM and 10 nM PDGF, whereas ET-3 and sarafotoxin S6b were less potent. These findings demonstrate that ET is a co-mitogen for rat vascular smooth muscle cells. The release of ET at sites of endothelial injury may therefore enhance the mitogenic action of locally acting PDGF on vascular smooth muscle cells and potentiate the proliferative response. PMID- 2102089 TI - Minorities in medicine: past, present, and future. AB - Since 1970 the Association of American Medical Colleges (AAMC) has had two key policies about minorities in medicine: (1) special attention should be paid to minority groups underrepresented in medicine, and (2) minority groups should be represented in medicine in the same proportions as in the population as a whole. Despite strong gains in the 1970s in increasing the number of black trainees and graduates, the proportion of minorities in medicine now is declining in relation to the total population. The paper discusses this situation, changes in U.S. minority populations, factors that affected the attempt to achieve parity in medicine, the current status of minorities in medical training (including educational debt) and on medical faculties, and remedies for institutions' lack of success in achieving parity. Three successful programs are described, as are the broader social issues that underlie academic medicine's attempt to increase the proportion of minorities in medicine. PMID- 2102091 TI - Changes in medical education should not ignore the basic sciences. PMID- 2102090 TI - New York's statewide approach to increase the number of minority applicants to medical school. AB - The Associated Medical Schools of New York (AMS), a consortium of 13 public and private medical schools, has identified the problem of low minority enrollment as its top priority issue. Over the last six years, the consortium has established a multifaceted, statewide effort aimed at increasing the pool of qualified minority applicants. The programs include academic enrichment for precollege and college students, recruitment conferences, and a program to attract minority applicants to residency training in New York. The key to this effort is the work of the AMS Office of Minority Affairs, which provides statewide oversight and coordinates these programs. The consortium approach has proven attractive to both private philanthropy and government funding sources and provides a mechanism for evaluation. The most valid evaluation will occur in about three years, when graduates of the precollege program begin to apply to medical school. PMID- 2102092 TI - First contact, simplified technology, or risk anticipation? Defining primary health care. PMID- 2102093 TI - Women's health: a focus for the 1990s. PMID- 2102094 TI - The paper trail versus the invisible college. PMID- 2102095 TI - Computer-assisted instruction and scientific method in medical schools. PMID- 2102096 TI - Students' role in establishing medical ethics program. PMID- 2102097 TI - Mistranslations. PMID- 2102098 TI - Development and evaluation of patient-oriented problem-solving materials in pharmacology. AB - Faculty from six eastern health science schools, from Florida to Nova Scotia, developed a new series of group-learning units during 1983 and 1984 using a recently developed patient-oriented problem-solving approach. The purpose of the units was to teach problem solving by applying the concepts and principles of pharmacology to therapeutic problems, and to find ways to engage students actively in their learning of this material. The development team envisioned that these goals would be met by means of well-crafted teaching units that could be evaluated and, if acceptable, used by academic pharmacologists in their teaching. The units were developed, edited, reviewed by experts, and field-tested with students at the authors' schools; editing and publication were done by the study's sponsor, the Upjohn Company. The results of the field trials (which indicated no need for revisions of the units) showed that the units were well crafted and that the students had higher scores on tests of their knowledge of pharmacology after they had used the units. PMID- 2102099 TI - Testing for validity and bias in the use of GPA and the MCAT in the selection of medical school students. AB - In the 1988 study reported here, Medical College Admissions test (MCAT) scores and grade point averages for undergraduate science courses (S-GPAs) were examined for predictive validity and differential prediction of National Board of Medical Examiners Part I scores. Data from 579 medical students from the classes of 1979 80 through 1983-84 attending a midwestern medical college were analyzed via moderated multiple regression. The findings indicated that using the S-GPA and a composite MCAT score based on the Biology Knowledge, Chemistry Knowledge, Physics Knowledge, Science Problems, and Reading subtests was valid and equally predictive for the minority and majority groups studied. These results are discussed in terms of past findings on cognitive tests in general, and the MCAT and the S-GPA specifically. PMID- 2102100 TI - An assessment of the student partnership program at the University of Missouri Kansas City School of Medicine. AB - The partnership program at the University of Missouri-Kansas City (UMKC) School of Medicine pairs less experienced students with more experienced students to work together during the last four years of a six-year curriculum. The present study has explored how the partnership program is supposed to work, whether in reality it does work, what function it actually serves, and under what circumstances it operates best. In 1986 and 1987, the authors analyzed information from formal school documents, created and used questionnaires for the students and faculty, conducted semistructured interviews with selected students, and used the results of an annual survey, begun in 1978, of supervisors of first year students who graduated from UMKC. The students and docents were found to favor the partnership system and reported that most partnerships worked well. The system's chief outcome is seen to be teaching teamwork: learning from and working together with student partners. The characteristics of the students, docents, and setting that contributed to successful partnerships are identified. The authors conclude that the partnership system at UMKC does achieve its objectives, which are described. PMID- 2102101 TI - Gender concordance between family practice residents and their patients in an ambulatory-care setting. AB - To determine whether women residents are more likely than men residents to treat female patients, the author analyzed data concerning resident-patient encounters in an ambulatory care setting from 107 family practice residents completing a university training program from 1979 through 1988. While the mean numbers of encounters for the men and women residents were similar, 70.5% of the women residents' encounters were with female patients, compared with 63.1% of men residents' encounters with female patients (p less than .0001). The women residents saw 3.6 times more female than male patients aged 13 to 20 years and 3.9 times more women than men patients aged 21 to 40. The women residents had more encounters for contraception, vaginitis, prenatal care, and health maintenance for women patients and fewer encounters for prostatic/testicular problems and health maintenance for men patients. PMID- 2102102 TI - How interruptions in students' medical education affect their clinical performance evaluations. AB - The enrollment records of 380 medical students from the graduating class of 1983 1988 at a four-year medical school were compared with the students' performances on two measures, third-year clinical rotation grades and National Board of Medical Examiners Part II examination (NBME-II) scores. Thirty-seven students (9.7%) interrupted their progress through medical school for negative (school initiated, academic) reasons or neutral (student-initiated, nonacademic, or personal) reasons. On both performance measures, the students in the neutral group performed similarly to regular-progress students and significantly better than students who interrupted their attendance in medical school for negative reasons. PMID- 2102103 TI - Examination-associated anxiety in students of medicine. AB - The authors studied 262 medical students who were in the second year at the University of Barcelona School of Medicine in 1988. The authors measured the students' anxiety as the students were taking each of two examinations on different subjects: one on medical psychology and one on physiology. The State Trait Anxiety Inventory questionnaire, recently validated in Spanish, was used to measure the students' anxiety associated with the examinations. In addition, analog scales were used to obtain the students' assessment of each examination's difficulty and its importance to them. The findings showed different levels of anxiety in examinations of different subject matters, with a positive correlation between the importance attributed to the examination and the associated anxiety, and a negative correlation between the importance of the examination and the importance attributed to chance in the marking. Implications of these findings and directions for future research are discussed. PMID- 2102104 TI - The effect on grades of the timing and site of third-year internal medicine clerkships. AB - Two important factors affecting the performances of third-year medical students on their basic internal medicine clerkships were investigated: (1) the effect on their grades of when in the academic year they took the internal medicine clerkship, and (2) the effect on their grades of the site of the clerkship. During the academic years 1983-84, 1984-85, and 1985-86, the Department of Internal Medicine of the University of Illinois College of Medicine at Chicago conducted 12-week junior clerkships at six hospital sites. The study analyzed the 535 students' subjective grades, clerkship examination scores, final grades, and National Board of Medical Examiners Part I (NBME-I) scores. Although students' performances as characterized by subjective evaluations did not improve as the academic year progressed, mean scores on clerkship examinations improved steadily during the same period. The site of the clerkship, whether a community-affiliated hospital or a medical center hospital, affected neither subjective nor objective grades. PMID- 2102105 TI - A follow-up survey of family physicians' interest in and knowledge of nutrition. AB - Forty-two practicing family physicians completed a questionnaire about 33 nutrition topic areas. They were among 71 physicians who, over an eight-year period (1980-1988), completed an identical questionnaire upon entry to their first postgraduate year in the family practice residency program at Brown University/Memorial Hospital of Rhode Island. Specific topic areas were grouped into five scales. Perceived knowledge of these topics significantly increased (p less than .0001) in all areas except nutritional biochemistry. There was significantly less (p less than .0001) interest in learning more about nutrition. One major exception was that the physicians wanted to learn more about nutrition counseling. Another exception was that nutrition in the life cycle remained an area about which they wanted to learn more. The physicians rated nutritional skills as less relevant on the second questionnaire than on the first. The authors conclude that more emphasis on nutrition counseling skills and nutrition in the life cycle may be appropriate in medical education. PMID- 2102106 TI - How internal medicine residents resolve conflicts with attending physicians. AB - Forty-three of 49 residents in an internal medicine residency answered questionnaires in 1988 about resolving conflicts with attending physicians concerning patient care, using ten case scenarios. The residents indicated their likelihoods of using various methods of addressing the conflicts via Likert-type scales. The residents were most likely to negotiate with the attending physician and least likely to ignore the attending physician or withdraw from the case for all scenarios, though the type of procedure affected the decision. The residents planning careers in general medicine or nonmedical specialties were more likely to agree with the attending physician than were the residents planning medicine subspecialty careers (p less than .005); the graduates from osteopathic schools were more likely to withdraw from the case than were the residents from allopathic schools (p = .05). Conflicts between the residents and attending physicians were resolved by negotiation and interaction with the attending physicians, but the nature of the procedure, medical school attended, and future career plans affected the means of resolving the dilemma chosen by the individual resident. PMID- 2102107 TI - An examination of two systems for inpatient housestaff training. PMID- 2102108 TI - Training residents to develop effective relationships with preceptors. PMID- 2102109 TI - The reliability of performance assessment during residency. PMID- 2102110 TI - Learning-style preferences and the satisfaction and performances of student groups. PMID- 2102111 TI - An ambulatory care internal medicine rotation for third-year medical students. PMID- 2102112 TI - Psychosocial aspects of HIV and AIDS and the evaluation of preventive strategies. PMID- 2102113 TI - Plasmid resistance to ampicillin in Salmonella typhi. AB - A Salmonella typhi strain resistant to ampicillin, streptomycin and sulfonamides was isolated in Catania in 1988. It has been shown that these resistances were encoded by an auto-transferable R-plasmid, of molecular weight 70 Md, belonging to the incompatibility group B. PMID- 2102115 TI - Clinical value of a new tumor marker (M.C.A.) in the breast cancer follow-up. AB - The authors evaluated the levels of a mucinous-like carcinoma antigen (M.C.A.) in the serum of 105 follow-up patients with breast carcinoma by means of an enzyme immunoassay. The negative/positive cut-off level determined in a group of healthy women was 13.2 U/ml. 80 patients turned out to be free disease, while 25 patients showed relapse or metastasis. High levels of MCA were observed in 72.0% of the patients with renewal of the neoplastic disease as well as in 12.5% of the free disease subjects. The EIA method appeared to have a good specificity (87.5%) and a fair test efficiency (83.8%). On the contrary, its sensitivity (72.0%) and its predictive value (64.3%) were not completely satisfactory. Therefore we think the matter needs to be studied more deeply and so does the case-report. PMID- 2102114 TI - Human neuronal cells in culture: from concepts to basic methodology. AB - The paper reviews some conceptual and methodological aspects of the tissue culture models which, during the past three decades, demonstrated a remarkable mimicry of many important structures and functions of the mammalian Central Nervous System (CNS) and related peripheral sensory and motor elements. Emphasis is placed on an original human neuronal tissue culture model obtained from selective CNS areas. The different cell types were identified and the neurotrophic interactions preliminary characterized. Neuropathological findings suggest hypothesis that can be fully tested using in vitro human models of affected cerebral specific areas. PMID- 2102116 TI - Soluble interleukin-2 receptor in vitro production by mononuclear cells from Hodgkin patients. AB - Lymphocytes of patients with Hodgkin's disease have a deficient production of Interleukin-2. Recently, a soluble form of the receptor for IL-2 has been demonstrated in human sera and in vitro-stimulated culture supernatants from human T lymphocytes. In the present paper we report the production of soluble IL 2R from peripheral blood mononuclear cells in H.D. The unstimulated MNC of patients released more sIL-2R than controls. No difference was observed between PHA-stimulated MNC of patients and controls. These preliminary findings suggest that soluble IL-2R may be provide a new tool for the study of immunological dysregulation in H.D. PMID- 2102117 TI - [Sensitization to ethylene oxide: a possible cause of reactions in hemodialysis patients]. AB - 147 hemodialyzed patient were studied for the presence of allergic reactions related to the dialytic treatment. Total IgE and specific IgE to common inhalants, ethylene oxide and phthalic anhydride were determined in all patients. The same determinations were also performed in two control groups. Specific IgE to ethylene oxide were detected in 7 sera. Among these 6 had a high total IgE level and 2 had a positive Phadiatop. Only 3 among the 7 positive patients had adverse reactions related to the hemodialysis (one suffered from itching, one from urticaria and the third from angioedema and hypotension). The resolution of the symptoms was obtained utilizing a gamma-rays sterilized filter. Therefore ethylene oxide sensitization may be a cause of some problems during hemodialysis. We couldn't find a relationship between atopic status and sensitization to ethylene oxide in as much in only 2 out of 7 patients sensitized to ethylene oxide, specific IgE to common inhalants were detected. PMID- 2102118 TI - Rapid identification of group B streptococci carriers. AB - Sensitivity and specificity of three commercial latex agglutination tests, i.e. Streptex, Wellcogen (Wellcome Diagnostics, Dartford, England) and Directigen (Becton Dickinson, Baltimore, USA) were evaluated on 233 vaginal swabs and 208 urine specimens after 4h culture in comparison with traditional cultural and identification methods. On vaginal swabs sensitivity of Wellcogen and Streptex was shown to be comparable (43% and 37% respectively), but both tests gave several false positive results; Directigen test showed higher (100%) specificity, but its sensitivity was very low. On urine cultures all the tests were shown to be unsatisfactory in comparison with traditional methods, sensitivity and specificity being demonstrated to be poor. PMID- 2102119 TI - Legionnaires' disease imported from Spain in a patient with beta-thalassaemia minor. AB - The Authors report a rare case of Legionnaires' disease imported from Spain in a patient with beta-thalassaemia minor. This condition as predisposing factor for Legionella pneumophila infection is discussed, with particular emphasis on the therapeutic implications. PMID- 2102120 TI - [Salmonella in the province of Livorno. Epidemiological study over the last five years]. AB - The authors refer on Salmonella species isolated from carriers, in USL 13 country, during the period of five years 1984-1988 in the microbiological laboratories of S.M.P. USL 13. N. 1240 Salmonella strains were isolated. N. 62 serotypes have been recognized of which about 77% were of the groups B, C1, E1. The trial shows a high positivity of more rare serotypes especially in summer period. PMID- 2102122 TI - Incidence of some infectious diseases in odontostomatology--section I. AB - In the medical studies there are many reports on the risk of being infected that the dental staff run, especially as far as it concerns viral diseases. The first worth is about the research into the problem of infections, in particular of viral hepatitis B, made by the Authors in the area of Modena. The results establish the potential presence of such risk; so, the Authors suggest to the people working in edental clinics to follow carefully the procedures of general and specific prevention. PMID- 2102121 TI - [Biological properties of an alcoholic extract of Aspergillus terreus]. AB - The following effects of Aspergillus terreus alcoholic extract are investigated: antiblastic and antiviral effect, and the ability of modification of interferon production and lymphocyte blastic transformation. In particular the extract showed more evident antiproliferative effect on transformed or EBV immortalised cells and lower effect on normal cells. Moreover doses from 12.5 +/- micrograms/ml depressed significatively the in vitro interferon production and lymphocyte blastic transformation induced by PHA on human cells. Mengo and Semliki Forest viruses replication was reduced, although temporarily, in the presence of 50 +/- micrograms/ml of the extract. Eventually the study of some fractions separated on chromatographic column demonstrated the contemporary presence of fractions able to inhibit or stimulate K-562 erythroleukemic cells replication. PMID- 2102123 TI - Extracranial-intracranial bypass to reduce the risk of ischemic stroke. AB - Extracranial-intracranial bypass surgery is an operative procedure in which the superficial temporal artery is anastomosed to the middle cerebral artery. The operation, first described in 1969, was employed to circumvent otherwise surgically inaccessible atherosclerotic lesions high in the internal carotid system or in the middle cerebral artery. This assessment compares the findings from 13 surgical series of EC-IC (1,464 patients) with those reported in the only prospective, randomized, cooperative trial of this procedure (1,377 patients). Analysis of the outcomes in the 1,464 patients included in the surgical series produced insufficient evidence to support a conclusion that post-EC-IC bypass stroke rates were lower than the rates of either the medically or surgically treated groups in the controlled clinical trial. In the absence of reliable, objective evidence of the existence of a group of patients in whom surgical intervention is superior to medical treatment in reducing the frequency of stroke, the results of the single controlled clinical trial, which demonstrated no benefit of bypass, must be accepted as the best evidence currently available. PMID- 2102124 TI - Finding the edge. 1: Providing an emergency service. AB - Many people find promoting their practice difficult at first, often not knowing how to start. The idea of advertising in the local newspaper or sending a letter to residents can seem alien to some people, yet there is no doubt that in an area where there are already several well-established practices a newcomer can often find the going very slow at first. One way to attract attention is to provide some special clinical service or different approach. This article is the first of a series which will feature how different dentists have used a number of ways to create that individual 'edge' to their services. In the first Richard Leworthy describes how he decided to set up an emergency service in his practice in Wells, in Somerset. PMID- 2102125 TI - Keeping in touch. AB - Letters, recalls, cards and most other forms of written communication are often taken for granted by both dentist and patients. Yet design and use of all written communication can play a significant role in practice promotion. In his second article Andy Lane has not only come up with some interesting ideas from his own practice, but has also highlighted the very real use he gets from a computer in handling the boring and repetitive side of making people feel special by the way you write to them. PMID- 2102126 TI - Practice brochures and newsletters. AB - One of Tom's great gifts is his enthusiasm for writing practice newsletters for his patients that he personalizes to communicate his caring attitude towards them. But beneath all that is a tremendous amount of hard work, discipline and dedication that he puts into producing these newsletters. We think the results are worth the effort, and that is why we decided to feature this article. PMID- 2102127 TI - How I became involved in marketing (and sometimes wish I hadn't). AB - The BDA has recently begun to take great strides forward in actually giving general practitioners what they want. You could say that the BDA has been taking notice of its own marketing advice by finding out what its customers want first and then looking at ways of providing it. This article by Mark Hargreaves is one example of this strategy, when Lynn Maris responded to an apparent need and organized an "In-Practice" course. Although the course itself has been reported in BDA News, we felt the concept needed a more in-depth analysis and a wider coverage. Judging from Mark's report we hope this is just the first of many such enterprises. PMID- 2102128 TI - First impressions count. Initial contact--receptionist. AB - Having visited many dental practices over the years, we are aware that from the patient's point of view the initial contact with the receptionist can be either extremely off-putting or an excellent introduction to the practice. This is so important that we suggest you try going to the practice of some colleagues unannounced to experience this for yourself. There is nothing like being treated as a patient in reception or on the telephone to bring home a few hard and unpleasant facts about the difficulty of getting this important area of patient care right. Herb Brathwaite has written an article which not only highlights the areas to look for, but also how to start taking action to improve your own reception if you wish. PMID- 2102129 TI - Marketing in dentistry--have we got it right? AB - This article has been written jointly by Ingried Morris, a dentist, and Sheila Scott, a marketing consultant. Ingried discusses some of the reasons why her colleagues may reject the marketing approach to dentistry, while Sheila argues that many of these skepticisms are indeed good reasons to embrace the discipline wholeheartedly. We felt that the article posed many questions, often unspoken, that worry a number of the profession who find it difficult harmonizing their perception of a commercial technique--marketing--with treating their patients in a caring profession. The article then goes on to answer those questions and suggests that true marketing is indeed caring, and can only strengthen the quality of clinical care. PMID- 2102130 TI - [Evaluation of acute and chronic effects of ketanserin in the treatment of hypertension and hypothesis on a new mechanism of action]. AB - Ketanserin is a specific antagonist of the 5-HT2 serotoninergic receptors; it is located on the smooth muscle cells of the vessel wall, and its stimulation causes vasoconstriction. The aim of this study is to evaluate the antihypertensive effect of ketanserin in patients with essential and secondary hypertension. Both systolic and diastolic blood pressure significantly decreased, in 18 patients, after chronic treatment with oral therapy (40-80 mg/day), and in 37 patients, after acute administration of sublingual (20 mg) and intravenous (10 mg) ketanserin. Acute administration of ketanserin was less effective than nifedipine (10 mg) in severe hypertension. Ketanserin, compared to placebo, permitted the normalization of blood pressure in 6/10 patients. Cardiovascular effects of ketanserin were studied with the ECOCG method in 8 patients with hypertension: peripheral resistances decreased, but left ventricular function and structure did not change. The effect of ketanserin on Na transmembrane transport systems in erythrocytes was studied both in vivo and in vitro, in order to evaluate the ketanserin action mechanism. The Na/K pump decreased and Na/Li countertransport increased, while different concentrations of serotonin did not change the transmembrane transport systems. In conclusion, ketanserin has a direct effect on transmembrane transport systems, not mediated by the serotonin receptors. This effect, with an antagonist of 5-HT2 serotoninergic and alpha 1 adrenergic receptor action, can cause a hypotensive effect. PMID- 2102131 TI - [Effects of serotoninergic block on reactivity of systemic and pulmonary circulation in hypertensive patients]. AB - The aim of this study was to verify the possible role of serotonin on vascular basal tone and over-reactivity in systemic and pulmonary circuits in hypertensive patients. We studied 15 hypertensive (G1) and 10 normotensive (G2) subjects. Right-side pressure and intravascular-arterial pressure measurements were obtained in baseline conditions and during alpha-adrenergic activation by cold pressor-test (CPT), before and after intravenous injection of ketanserin 10 mg (K), an S2-receptor antagonist. Systemic and pulmonary pressures and resistances were higher in G1 than in G2 in the steady state. K induced a significant reduction of both pressures and resistances in G1, no change in systemic response to CPT in the 2 groups and a significant reduction in the pulmonary vascular reactivity to adrenergic stimulus only in G1. These data confirm the vasodilator action of serotonin-blockade. The observation of vasodilatation in pulmonary circulation is not in favor of its dependence on vascular endothelium damage. In fact the arterial endothelium lesions due to hypertension are present only in the systemic circuit. Concerning result of CPT: 1) serotonin doesn't seem responsible for vascular over-reactivity in hypertension, unchanged by K; 2) the particular pattern of pulmonary vascular contractility in G1 may be interpreted as resulting from an elective depressive action of S2-blockade, depending on a different distribution of S1 and S2 receptors in the two circuits. PMID- 2102132 TI - [Changes in serotoninergic mechanisms in essential hypertension]. AB - Several data suggest the possible involvement of serotonin (5HT) and of the serotoninergic (5HTergic) system in the pathophysiology of essential hypertension. Our study aim was thus to measure a peripheral 5HTergic marker, such as platelet 5HT uptake, in 8 hypertensive patients, as compared with healthy controls. All subjects included underwent evaluation of the pain threshold, in view of the possible relationship between mechanisms involved in pain modulation and those regulating blood pressure. The results showed a decrease of the maximal velocity (Vmax) of platelet 5HT uptake in the patients, who also exhibited an increase in the pain threshold. These data, although preliminary, are suggestive with regard to an increased concentration of extraplatelet 5HT, which might play a role in both hypertension and the change in pain threshold. PMID- 2102133 TI - [Humoral and hemodynamic (systemic and renal) effects of ketanserin in patients with essential hypertension: what is the role of prostaglandins?]. AB - We have studied the hemodynamic and humoral effects of ketanserin, an S2 antagonist, and whether PG synthesis blockade, induced by indomethacin, might modify its effects. Eight patients with uncomplicated essential hypertension were submitted to a treatment for three days with indomethacin (50 mg/b.i.d.) and for 3 days with placebo. At the end of each period, saline and ketanserin (10 mg i.v.) were given. The effects of placebo and of ketanserin were assessed for one hour by measuring the following parameters: blood pressure (BP), heart rate (HR), renal plasma flow (RPF), glomerular filtration rate (GFR), renal vascular resistance (RVR), PRA, aldosterone, noradrenaline (NA) serum and urinary thromboxane, urinary 6-keto-PGF1 alpha. Under placebo and as compared in saline, ketanserin significantly reduced BP aldosterone and RVR and increased HR, GFR, PRA, NA, serum and urinary thromboxane and urinary 6-keto-PGF1 alpha without modifying RPF. Pretreatment with indomethacin which significantly reduced serum thromboxane and urinary thromboxane and 6-keto-PGF 1 alpha prevented the renin stimulating effect and the increase in GFR induced by ketanserin without changing the other actions of this drug. Taken together, these findings indicate that PG do not play a relevant role in the antihypertensive effect of ketanserin, but mediate the GFR increase induced by this drug. PMID- 2102134 TI - [Effects of chronic antihypertensive treatment with ketanserin versus metoprolol on blood pressure and compliance of great arteries in man: a double-blind crossover study]. AB - The antihypertensive efficacy of a receptor antagonist of serotonin was compared with a widely known antihypertensive drug, metoprolol, and their effects on cardiac and forearm hemodynamics were studied using echocardiography and flowmetry with pulsed bidimensional Doppler. Twenty patients with hypertension completed a randomized double-blind crossover study, using ketanserin and metoprolol. Two periods of 5 weeks with ketanserin or metoprolol were preceded by a placebo period the total duration of the study was 15 weeks. Although comparable efficacy in reducing systolic and diastolic pressure, (by about 10% of base-values), was observed, the two drugs showed quite different effects on forearm hemodynamics. Ketanserin increased blood flow to the forearm and induced a significant decrease in the vascular resistances of the forearm (from 141 +/- 16 to 75 +/- 11 mmHg/mL/s; p less than 0.01). Moreover, this treatment was able to improve the compliance of the brachial artery (from 1.89 +/- 0.3 to 3.2 +/- 0.3 cm4/dyn 10(-10); p less than 0.01). On the contrary, metoprolol did not modify forearm hemodynamics. Neither drug modified cardiac performance, as assessed by the circumferential shortening of the fibers of the left ventricle. Cardiac output was increased by ketanserin (from 5.9 +/- 0.3 to 6.6 +/- 0.5 L/min; p less than 0.05) and reduced during treatment with metoprolol (from 5.9 +/- 0.4 to 4.9 +/- 0.3 L/min; p less than 0.01). Thus the two drugs reduced arterial pressure by different hemodynamic mechanisms and the effects of ketanserin on systemic and peripheral circulation seem more favourable. PMID- 2102135 TI - [Clinical and hemodynamic effects of medium-term treatment with ketanserin of 2 comparative groups of obese and non-obese hypertensive patients]. AB - We evaluated systemic and central hemodynamics in 10 lean hypertensives and in 10 obese hypertensives (WHO stage I-II) after 8 weeks treatment regimen with a serotoninergic antagonist such as ketanserin. At the beginning and the end of the study, body weight, BMI, blood pressure and heart rate were measured and a first pass radionuclide angiocardiography was performed to determine cardiac output, cardiac index and ejection fraction of left ventricle. Total peripheral resistances were also calculated. In both hypertensive groups ketanserin significantly reduced diastolic (p less than 0,05) and mean (p less than 0.005) blood pressure. No significant change in systolic blood pressure, cardiac output, cardiac index and ejection fraction was observed in lean or obese hypertensives. Total peripheral resistance values significantly (p less than 0,05) decreased in lean hypertensives; in obese hypertensives total peripheral resistance was moderately reduced. Our results indicate that monotherapy with ketanserin is effective in treating mild to moderate hypertension in both lean and obese hypertensives and does not interfere with left ventricular performance. In conclusion the effectiveness of ketanserin treatment appears moderately higher in lean than in obese hypertensives. PMID- 2102136 TI - [Hemodynamic and humoral effects of 2 different doses of ketanserin in aged patients with hypertension]. AB - The purpose of this double blind, cross-over, randomized study was to assess the antihypertensive efficacy and tolerability of ketanserin given at two different doses (i.e. 20 or 40 mg b.i.d.) in a group of patients with essential hypertension aged over 60 years. In addition, we evaluated the effect of ketanserin on some indexes of the sympathetic nervous system activity and the renin-angiotensin-aldosterone system, as well as the pharmacokinetic characteristics of the drug after acute administration per os and during chronic treatment. Twelve hypertensive patients, 6 males and 6 females gave their informed consent to the study. Each patient underwent a non invasive blood pressure monitoring after a wash out period with placebo, after 5 weeks of treatment with ketanserin (20 or 40 mg b.i.d.), after a second wash out period with placebo, and after a second period of treatment (5 weeks) with ketanserin (40 or 20 mg b.i.d.). In addition, we evaluated ketanserin plasma levels during acute and chronic administration. During treatment with ketanserin 20 mg b.i.d. systolic and diastolic blood pressure showed a small, statistically not significant reduction. The higher dose (40 mg b.i.d.) reduced systolic and diastolic blood pressure. Three hours after administration of 40 mg of the drug, ketanserin plasma levels were higher than after administration of 20 mg; this difference disappeared after 24 hours. A statistically significant relationship between mean blood pressure reduction during chronic treatment and ketanserin plasma levels was detected. No adverse effects were detected. In conclusion, ketanserin seems to be well tolerated and useful in antihypertensive therapy in elderly patients, particularly at the dose of 40 mg b.i.d. PMID- 2102137 TI - [Serotonin and hypertension in preeclampsia-eclampsia syndrome]. AB - The preeclampsia-eclampsia syndrome is a severe complication of the third trimester of pregnancy and represents the first cause of maternal death. It is mainly characterized by: weight increase, proteinuria and hypertension and can evolve with convulsions and maternal death. The etiology still remains unknown although a series of events have been identified, starting with endothelial damage and local vasoconstriction leading to hypertension. These events occur at first locally in the placental district and become generalized. This paper reports experimental and clinical data in order to demonstrate: 1) the presence of a substance that could evoke experimentally the damage present in this syndrome, 2) a mechanism that delivers such a substance to its primary action site, the placenta, and 3) the possibility to inhibit either the substance or the delivery mechanism in order to prevent this disease. Serotonin appears to play an important role in the chain of events leading to preeclampsia. Certain histological aspects, present in pregnant women with this type of hypertension, have been observed in experimental animals after the administration of serotonin. Platelet derived serotonin could be sufficient, in the case of endothelial damage, to determine vasospasm. In a condition of hypercoagulability, such as pregnancy, this situation can trigger a chain of mechanisms ending with renal damage. Low dose aspirin seems a valid therapeutic approach reducing thromboxane concentrations and therefore preventing vasospasm. In this way the pathogenetic sequence culminating in the preeclampsia-eclampsia syndrome is interrupted. Ketanserin inhibits the hypertensive potential of serotonin by selectively acting on S2 serotonin receptors and appears to be an effective treatment in this type of pregnancy induced hypertension. PMID- 2102138 TI - [Effects of treatment with ACE and serotonin inhibitors on arterial blood pressure at rest and cycloergometric exercise and on systolic time intervals: comparison of enalapril and ketanserin]. AB - Exercise tolerance test gives important diagnostic, prognostic and therapeutic information in hypertensive patients. One hundred essential hypertensive patients were treated with enalapril: 10 mg/day, ketanserin: 40 mg/day and associated enalapril: 5mg/day + ketanserin: 20 mg/day for three different periods of three months for each one, with a wash-out period of 15 days after each therapeutic cycle. We used ACE and ketanserin because they have a hypotensive effect without developing tolerance, metabolic effects, rebound events in case of sudden interruption. These pharmacologic agents, which are active by themselves, can also be used in association with other hypotensive agents. Two exercise tolerance tests were carried out on each patient before and after each therapeutic period. Clinostatic systolic time intervals were assessed before and after treatment. Enalapril and ketanserin reduced systolic and diastolic pressure in basal condition and after exercise tolerance test, without any interference on heart rate. The association of the two hypotensive agents resulted more active, even with a halved dose. The improving of the double product and the systolic time intervals confirm the efficacy of these treatments. Side effects were mild. PMID- 2102139 TI - Beta-carotene and cancer. PMID- 2102140 TI - The role of extra-anatomic grafts for lower limb ischaemia. AB - Aorto-bifemoral graft is the conventional treatment for ischaemic lower limbs due to severe aorto-iliac disease. However, some patients are not fit to withstand this major procedure, and for them extra-anatomic grafts provide a method of improving the blood supply to the legs where the alternative may be amputation. The role of these grafts has still not been established because of variable results. We have used the femoro-femoral and the axillo-femoral routes for ten years. The patients were unfit for major surgery and had an overall mortality of 20% in two years. They all presented with critical lower limb ischaemia. Forty three extra-anatomic grafts have been inserted. Perioperative mortality was less than 2%. None of those undergoing femoro-femoral grafting required subsequent amputation: four amputations were performed in those with axillo-femoral grafts. We conclude that extra-anatomic grafts should be considered before resorting to amputation in patients with critical lower limb ischaemia. PMID- 2102141 TI - Patient management following uncomplicated elective gastrointestinal operations. AB - The management of patients after uncomplicated elective gastrointestinal operations is frequently left to junior members of the surgical team once they have learnt their seniors' regimens. The use of nasogastric (N/G) tubes, the volume of intravenous (IV) fluid replacement and the reintroduction of oral fluids and solids are topics not generally covered in the surgical textbooks and so are learnt in hospital. A postal survey of all consultant general surgeons in Scotland was conducted to assess the variations in management of patients after cholecystectomy, right haemicolectomy and sigmoid colectomy. A completed questionnaire was received from 111 (81%) of the surgeons circulated. As might be expected, patient management varied widely from surgeon to surgeon, and from unit to unit. There would appear to be a need for prospective studies in this area of patient management. This may indicate that the use of N/G tubes could be further reduced and that oral fluids and solids could be reintroduced sooner after operation with improved patient comfort and reduced hospital stay, yet without detriment to patient care. PMID- 2102142 TI - Acoustic reflectometry as an aid to the diagnosis of glue ear. AB - In assessing the usefulness of the acoustic reflectometer we have evaluated its performance on a selected group of patients, finding it to be of equivalent predictive value to those screening tests in common use. We feel that the advantages of the instrument combined with its performance will provide the general practitioner with a useful diagnostic aid. PMID- 2102143 TI - Hypertensive disorders of pregnancy and gestational diabetes mellitus in mature gravidae. PMID- 2102144 TI - Ingrowing toenails: studies of segmental chemical ablation. AB - Recent studies have suggested that segmental ablation is the treatment of choice for patients with ingrowing toenails and that the success rate is 96%. This procedure has been common practice among chiropodists for 20 years, usually using phenol in the United Kingdom, and sodium hydroxide in the United States. However, there has been little critical evaluation of the relative merits of the two chemicals, of the period of chemical application, or of the duration of post operative pain and healing time. We therefore embarked upon a number of controlled prospective studies to examine these questions. A prospective study of 422 procedures for patients with ingrowing toenails (onychocryptosis) shows that good results are achieved by segmental chemical ablation performed by chiropodists in 91% of cases. The average period of post-operative pain is 3.6 days. Similar results are obtained using either 80% phenol or 10% sodium hydroxide. We believe that segmental chemical ablation by a chiropodist is the treatment of choice for the typical patient with an ingrowing toe nail. PMID- 2102145 TI - Clinical experience with pefloxacin in patients with urinary tract infections. AB - A total of 27 patients, 21 of them females, with a median age of 56 were treated with pefloxacin for urinary tract infections. Some 74% of these infections were associated with upper tract symptoms, and Escherichia coli was the most common causative micro-organism (75% of cases). Fifteen patients had co-existent diseases with/without urological abnormalities. All strains of E coli were sensitive to pefloxacin; Actinobacter and one strain of Klebsiella and Streptococcus faecalis were resistant. Two patients who defaulted and one who had an initial negative bacterial culture were excluded from the analysis of the outcome. The overall bacteriological cure rate at four to eight weeks was 87.5% (21/24). The incidence of possible side-effects was high, occurring in 59% of the patients. Nausea, dizziness and vomiting were the most common. These were mild and did not require termination of treatment. Peripheral neuropathy, which disappeared four weeks after stopping pefloxacin, occurred in one patient. PMID- 2102146 TI - Architectural glass injuries: a case for effective prevention. AB - Nine hundred and eighteen patients with glass-related injuries were studied retrospectively. Forty per cent of the injuries were due to architectural glass, which resulted in more severe injuries, required more complicated plastic/surgical repairs and needed longer treatment time. It also produced more disabilities in all age groups. These injuries can be prevented by the use of safety glass in residential buildings, a usage which should be legally enforced as in the USA. PMID- 2102147 TI - Unexpected ovarian cysts found at appendicectomy: attitudes to management. PMID- 2102148 TI - Serum aldolase with creatine kinase in current clinical practice. AB - To devise a clinical laboratory policy for serum aldolase (ALD) requests, the use of ALD alone and in conjunction with serum creatine kinase (CK) was studied in 126 consecutive patients. Both enzymes were normal in 76 cases (60.3%); CK was normal but ALD was raised in 19 cases (15.1%); ALD was normal but CK raised in nine cases (7.1%); and both were raised in 16 (12.7%). The spectrum of disease was similar irrespective of the enzymes elevated. The role of ALD in the diagnosis and monitoring of muscle disease is in those cases where CK falls within the reference range. PMID- 2102149 TI - The role of incomplete pulmonary inactivation of metabolites in the association of prepatellar bursitis with asthma. PMID- 2102150 TI - Maternal response to anomalies detected by antenatal ultrasonography. AB - OBJECTIVE: To determine the effect of an atypical antenatal scan on the expectant mother. DESIGN: Postnatal postal questionnaire. SETTING: Questionnaires completed at home after the infants had been investigated at a regional paediatric surgical unit. SUBJECTS: Twenty-nine mothers. RESULTS: The mothers had a very positive attitude to antenatal ultrasonography. The information that the scan was atypical resulted in a high level of parental anxiety which sometimes persisted into the postnatal period. CONCLUSION: A multidisciplinary approach is required for the management of the expectant mother who has an atypical scan. PMID- 2102151 TI - A microcomputer program to compare the survival probability of patient groups. AB - A program was written to calculate the probability of patient survival, tabulate the results in the form of a life table and compare two patient groups by the Mantel-Haenszel (logrank) test on a microcomputer. The program reads data in either a text form or the format of data files of the dBASE III/III plus (Ashton Tate). The program is entirely menu-driven and extremely easy to use. The structure of the data files and the function of the program are described. This program is useful to those without easy access to mainframe computers. PMID- 2102152 TI - Cholecystostomy: a safe alternative? AB - We have studied retrospectively 27 patients undergoing cholecystostomy for acute cholecystitis over the past decade. The mean age of the patients was 60 years, and 17 were female. 'Difficult dissection' was the reason given for cholecystostomy in 18 cases and in the remainder the patients were deemed unfit for cholecystectomy. An operative cholangiogram was performed in only two cases, and none of the patients had a primary common bile duct exploration. Post operative cholangiograms in 14 patients revealed common bile duct stones in three (21%). Three elderly patients (mean age 79) died in hospital. At a mean follow-up of one year, 26% of patients had come to elective cholecystectomy, and there had been a further three unrelated deaths. We conclude that under difficult circumstances, cholecystostomy may be a safe alternative to cholecystectomy. These patients have a high incidence of choledocholithiasis, and thus we would recommend operative cholangiograms in all patients. However, early ERCP and sphincterotomy may be a safe alternative if this service becomes more widely available. PMID- 2102153 TI - Observations on herpes zoster: 1. Residual scarring and post-herpetic neuralgia; 2. Handedness and the risk of infection. AB - The risk of developing post-herpetic neuralgia is related to the degree of residual scarring. Subjects over the age of 60 with more than 10 cm2 of residual scarring have a very high risk of developing intractable post-herpetic neuralgia. Left-handed subjects are less likely to develop herpes zoster, and this could be due to a more efficient immune system. PMID- 2102154 TI - Genito-urinary tuberculosis: a review of 83 cases. AB - We evaluated 83 cases of genito-urinary tuberculosis retrospectively. Flank pain and non-specific urinary complaints were the major symptoms. Although some authors prefer short-term medical therapy, the relapse rate in our series with six-month therapy was 22%, and we therefore suggest a therapy period of at least 12 months is necessary. The poor nutritional status and social conditions characteristic of subjects from our region may, however, be a factor in this high relapse rate. PMID- 2102155 TI - What is collapse? A differential diagnosis in the elderly. PMID- 2102156 TI - The spectrum of acute intestinal vascular failure: a collective review of 43 cases in Taiwan. AB - High mortality rates associated with mesenteric ischaemia are a tremendous challenge. We reviewed 43 patients admitted to Chang Gung Memorial Hospital between 1981 and 1988. A total of 24 patients (55.8%) had thrombosis or embolus of the superior mesenteric artery, five patients (11.6%) had superior mesenteric vein thrombosis, and 14 patients (32.6%) had non-occlusive infarction. Patients with mechanical obstructions (volvulus, intussusception, tumour compression, aortic dissection) causing mesenteric ischaemia were excluded. The initial symptoms were not specific before signs of peritonitis presented. The tetrad of leucocytosis (88.4%), metabolic acidosis (88.6%), hyperamylasaemia (46.9%) and elevated phosphate (33.3%) was noted to be significant. There was a high association with previous cardiovascular diseases (78.2%). The plain abdominal X ray, which was the most frequently used investigative tool, showed suggestive but non-specific findings. A total of 38 patients (88.4%) were operated upon. In six patients (14%) the exploratory laparotomy was open and closed because the bowel gangrene was too extensive. The total mortality rate was 55.8%. To improve prognosis, clinical awareness of the problem should be raised and the use of mesenteric angiography should be encouraged in an attempt to obtain an early diagnosis. PMID- 2102157 TI - The incidence of recurrent soft tissue ankle injuries. AB - A prospective study was carried out to assess the incidence of recurrent soft tissue injuries to the ankle joint. Out of 310 patients with acute ankle injuries seen in the accident and emergency department at the Royal Victoria Infirmary, Newcastle upon Tyne, 101 (32.5%) had injuries which were severe enough to necessitate review in the follow-up clinic. Twenty-seven of these patients (26.7%) had sustained one or more previous injuries to the same ankle within the past 24 months. This rather high incidence of recurrence highlights the need to evaluate our current diagnostic and treatment policies in dealing with this common injury. PMID- 2102158 TI - Hydatid disease of the liver: current surgical management. AB - We present our experiences with 44 cases of hydatid disease of the liver. Two thirds were females, and the average age was 44. The most common symptom was abdominal pain (63.6%), and the most common sign was abdominal mass (48%). Eosinophilia, positive Weinberg and Cassoni tests, ultrasonography and CT scanning were the major tools for diagnosis. There were 67 cysts, 49 (73%) located at the right lobe, 18 (27%) located at the left lobe. Twelve (18%) were complicated. The most common complication was intrabiliary rupture. After evacuation of the cyst, we managed the cyst cavity with one or more of the following procedures: omentoplasty, tube drainage, capitonnage, partial cystectomy, cystectomy and scolicidal agent injection. Infected cases were drained, and choledochotomy and internal or external drainage were performed for intrabiliary ruptured cases. Tube drainage and omentoplasty did not increase mortality. Average hospital stay was 11 days. There was no operative mortality. PMID- 2102159 TI - Postpartum homeopathic Arnica montana: a potency-finding pilot study. PMID- 2102160 TI - A retrospective study to assess the migraine headache remission rate after cessation of pizotifen therapy. PMID- 2102161 TI - The aetiology of bleeding peptic ulcer--as observed in a district general hospital. AB - A review was made of the hospital case notes of 124 patients admitted with symptoms of upper gastrointestinal haemorrhage due to bleeding peptic ulcer over a five-year period. A high proportion of the patients were found to be elderly and female, as observed by Walt et al 1986. This finding was more pronounced if the source of the bleed was a gastric ulcer. Many of these elderly patients had been on anti-inflammatory drugs at the time of presentation. Concomitant treatment with cimetidine or demulcents did not seem to prevent episodes of bleeding. Many patients on anti-inflammatory drugs bled repeatedly after apparently adequate medical or surgical treatment. PMID- 2102162 TI - Anorexia nervosa in the elderly: a case report and review of the literature. AB - Anorexia nervosa is a rare disorder in the elderly but should be thought of in the differential diagnosis of extreme weight loss, especially if there are accompanying psychological features and normal baseline investigations. Psychiatric opinion should be obtained and treatment, although of unproven value, considered, since improvement may increase mobility and reduce morbidity and mortality. PMID- 2102163 TI - Tuberculous appendicitis with perforation. AB - A young female who had been investigated for vague abdominal complaints and marked loss of weight was discovered only after laparotomy, carried out for acute appendicitis, to have primary tuberculosis of the vermiform appendix with perforation. The rarity of tuberculosis of the appendix, the types of presentation and the pitfalls of diagnosis are discussed. The literature on appendicular tuberculosis is reviewed. PMID- 2102164 TI - Erythroleukaemia and daunorubicin-induced cardiotoxicity in a young boy. PMID- 2102165 TI - A rare mimic of testicular cancer. PMID- 2102166 TI - Subarachnoid haemorrhage mimicking acute water intoxication during labour augmented by oxytocin infusion. PMID- 2102167 TI - Duodenal obstruction (Bouveret's syndrome) and jaundice due to a single large gallstone. PMID- 2102168 TI - Life-threatening peripharyngeal sepsis with mediastinitis. AB - A case of life-threatening peripharyngeal sepsis with mediastinitis is described. The pathology, relevant anatomy and treatment are discussed and the literature is reviewed. PMID- 2102169 TI - Primary spinal epidural non-Hodgkin's lymphoma. PMID- 2102170 TI - Experience of scapula winging in an accident and emergency department. PMID- 2102171 TI - Acute appendicitis associated with pneumoperitoneum. AB - Spontaneous pneumoperitoneum is infrequently encountered as a radiographic finding in association with a perforated appendicitis. This may lead to diagnostic errors, of which every radiologist and surgeon should be aware. We report a case of perforated appendicitis associated with free intraperitoneal gas. PMID- 2102172 TI - Foreign body perforation of the ileum. PMID- 2102173 TI - Remember primary peritonitis. AB - Two cases of primary peritonitis are reported. One, which we believe to be the first case reported in an elderly female, raised our index of suspicion and thus enabled the second case to be diagnosed by fine-needle paracentesis and treated without operation. Both cases outline the inadequacy of prophylactic antibiotic cover with a cephalosporin and metronidazole. The case reports are followed by a general discussion outlining the incidence, aetiology and treatment of primary peritonitis. PMID- 2102174 TI - Idiopathic mesenteric venous thrombosis. PMID- 2102175 TI - Malignant Langerhans' cell histiocytosis of the clavicle: a rare pathological fracture. AB - Langerhans' cell histiocytosis (LCH) is an extremely heterogeneous disorder which is uncommon, making therapeutic guidelines difficult. The malignant features seen in this case have been described presenting in the skin but not in the bone. Although pathological fractures through bone affected by eosinophilic granuloma have been described, this is the first reported case of LCH with malignant features presenting in such a way. PMID- 2102176 TI - Amputation for reflex sympathetic dystrophy. PMID- 2102177 TI - Hind-quarter amputation in a paraplegic with a neuropathic and septic hip joint. PMID- 2102178 TI - Endometriosis of the sigmoid colon: a diagnostic problem. AB - Colonic endometriosis is often difficult to diagnose pre-operatively and most cases are diagnosed postoperatively from histology. The main problems with pre operative diagnosis are due to the radiographic similarities between endometriosis and malignant lesions and the difficulties in obtaining satisfactory biopsy material. PMID- 2102179 TI - Abdominal tuberculosis mimicking lymphoma in a patient with sickle cell anaemia. PMID- 2102180 TI - Plastibell circumcision. AB - A complication of Plastibell circumcision requiring hospital admission is described. This occurred in three siblings of different ages who were circumcised at the same time by a non-medical religious operator. The complication was caused by proximal dislocation of the Plastibell ring, which failed to fall off at the usual time. In one case a general anaesthetic was required to remove the ring. Careful observation, by informed parents, after such a procedure will allow early intervention which should prevent such an occurrence. PMID- 2102181 TI - The normal IVU: a trap for the unwary. AB - Intravenous urography (IVU) is considered to be a reliable means of investigating the urinary tract for renal pathology. We present two cases of patients who were investigated for loin pains. In both patients the IVU appearances were normal but the final diagnosis, as obtained by ultrasound, was renal cell carcinoma of the upper pole of the right kidney. PMID- 2102182 TI - Bilateral subdural haematomas and normal CT brain scans. AB - We describe the case of a 59-year-old man who presented with headaches suggestive of raised intracranial pressure. He had a normal computerised tomographic (CT) scan on two occasions over a period of two months during which time he continued to deteriorate. Eventually, a magnetic resonance imaging (MRI) scan showed the presence of bilateral subdural haematomas. This case thus illustrates that normal CT scans may not exclude an intracranial pathology--and, if in doubt, an MRI scan should be sought. PMID- 2102183 TI - Neuromyelitis optica (Devic's disease). PMID- 2102184 TI - Pulsatile varicose veins--a sign of tricuspid regurgitation. PMID- 2102185 TI - Splenic and renal abscesses following Salmonella virchow septicaemia- conservative management with ciprofloxacin. AB - Splenic abscess formation is a serious condition which usually requires prompt surgical intervention. We report on a patient with Salmonella virchow septicaemia, complicated by peritonitis and multiple splenic and renal abscesses. This is an uncommon manifestation of non-typhoid salmonella infection, which was managed conservatively with oral ciprofloxacin, leading to satisfactory resolution and cure. PMID- 2102186 TI - Arterial embolus and iliac aneurysm following total hip replacement. PMID- 2102187 TI - Osteolytic lesions in chronic myelomonocytic leukaemia. PMID- 2102188 TI - Spontaneous haemoperitoneum in a young man. PMID- 2102189 TI - Acute carpal tunnel syndrome in haemophiliacs. AB - Acute median nerve compression at the wrist differs from the classical carpal tunnel syndrome in its aetiology and presentation. There is a rare association with haemophilia and such a case is reported in this paper. A review of the literature over the past 20 years revealed only nine cases. It is suggested that management should be conservative in the first instance, with factor VIII replacement continued for three to five days. Surgical decompression is indicated if symptoms fail to resolve in the first 24 hours. PMID- 2102190 TI - Tracheal infiltration causing stridor: a rare presentation of stage I Hodgkin's disease. AB - Tracheal neoplasms are easily missed until a late stage, but an accurate histological diagnosis can lead to a very worthwhile result. A case of Hodgkin's disease presenting with stridor due to tracheal infiltration, diagnosed following an endometrial biopsy and treated successfully with external beam radiotherapy, is here reported upon. PMID- 2102191 TI - Gastric stricture complicating oral ingestion of bleach. PMID- 2102192 TI - Colovesical fistula caused by appendicitis. AB - A case of colovesical fistula in a 51-year-old male patient is described. The connection, between the base of the bladder and the rectosigmoid junction, was caused by an appendicitis in the tip of a pelvic appendix which had perforated into the bladder and rectosigmoid. There was no appendicovesical fistula connecting with the caecum. PMID- 2102193 TI - Hypophosphataemic hypercalcaemia in an acutely ill patient. PMID- 2102194 TI - Primary sarcoma of the lung: potential dangers of immunocytochemistry. AB - A case is presented of a successfully resected primary pulmonary sarcoma in a 27 year-old man, followed by an eight-year disease-free follow-up. Details of the histological findings are presented, and the factors associated with good prognosis discussed. Immunocytochemical stains were carried out this year when the case was reviewed, and not at the time of resection. Had the immunostains been available at the time, the results would have suggested that the tumour might be a secondary deposit, and so have caused needless anxiety to the patient and his physicians. PMID- 2102195 TI - Uterine leiomyoma causing retained placenta. PMID- 2102196 TI - New bone formation after tumour resection. PMID- 2102197 TI - Transcatheter embolisation of a suprarenal aortic aneurysm persisting after bypass graft surgery. AB - We present a case of a large suprarenal aneurysm which recurred following aorto biliac bypass grafting and ligation of the aneurysm. Successful thrombosis was achieved with selective embolisation. PMID- 2102198 TI - An unusual case of abdominal apoplexy. PMID- 2102199 TI - Haemorrhage within an intracranial meningioma associated with chronic subdural haematoma. PMID- 2102200 TI - A unique case of Munchausen's syndrome. AB - A most unusual case of Munchausen's syndrome in an 18-year-old Yemeni female is described. The patient presented with bleeding from various sites; repeated subcutaneous emphysema of the face, orbit and upper chest; ulcers on the tongue, and dermatitis autogenica. The illness was confirmed to be factitious and self induced when she was caught red-handed trying to inject air. We believe this to be the first report of a case where all these features occurred concurrently and only the second report where a patient developed self-induced orbital emphysema. PMID- 2102201 TI - Ten-year survival following resection of an adrenal neuroblastoma with multiple liver metastases. PMID- 2102202 TI - Giant ganglion of the superior tibio-fibular joint. PMID- 2102203 TI - Anti-tuberculous drugs and sideroblastic anaemia. AB - Two cases of sideroblastic anaemia associated with antituberculous therapy are reported. The first, in whom there was a constitutional chromosomal abnormality and peripheral neuropathy, recovered on withdrawal of isoniazid and pyridoxine treatment. The other, who had been given a four-drug combination including isoniazid and pyrazinamide and recovered on the withdrawal of isoniazid alone, highlights the increasing likelihood of this complication in patients treated for tuberculosis, since this drug combination has regained popularity in recent years. PMID- 2102204 TI - Clostridium septicum gas gangrene following intramuscular infection from an influenza vaccine booster. AB - We have reported a case of C septicum gas gangrene occurring in the forearm of a patient who had an Influvac influenza booster 48 hours before admission. Despite prompt antibiotic treatment and surgical debridement, the patient became hypotensive and could not be resuscitated. PMID- 2102205 TI - Management of candidiasis in the surgical patient. PMID- 2102206 TI - Pyoderma gangrenosum of the breast. PMID- 2102207 TI - Blastocystis hominis: an unusual cause of diarrhoea. PMID- 2102208 TI - Severe hypercalcaemia and tamoxifen 'flare'. PMID- 2102209 TI - Acute spontaneous subdural haematoma of arterial origin. PMID- 2102210 TI - Feto-pelvic disproportion of mimicking placental abruption. AB - An unbooked patient presented with severe eclampsia and sudden onset of abdominal pain, uterine tenderness and fresh vaginal bleeding. Unsuspected macrosomia and multiple congenital fetal malformation were discovered at delivery and a neonate weighing 7.545 kg was delivered. The infant died shortly afterwards. PMID- 2102211 TI - Prostatic carcinoma presenting as left supraclavicular lymphadenopathy. PMID- 2102212 TI - An allergic reaction to intravenous methylprednisolone administration. AB - A 60-year-old woman with acute asthma developed generalised urticaria and rapidly worsening bronchospasm immediately after IV administration of methylprednisolone sodium succinate. Subsequent skin testing was positive for this, but for no other corticosteroid. Later, both IV dexamethasone during a recurrent attack and oral prednisone for panhypopituitarism were well tolerated. This patient and a review of the literature reveal that corticosteroids are a very rare but important cause of anaphylaxis-like reaction. PMID- 2102213 TI - Appendicitis and occult carcinoma of the caecum. AB - Appendicitis can occur rarely in association with carcinoma of the caecum, particularly in the elderly. If this possibility is not appreciated and thorough laparotomy is not carried out at the time of initial surgery, an early malignant lesion may go unrecognised. In this situation, if appendicectomy is performed, it will need to be revised to a right hemicolectomy at a later date. Survival chances are then affected adversely due to the possibility of early dissemination of malignant disease through the breaching of intestinal integrity and tumour cell spillage. Two cases are reported where carcinomatous recurrence occurred in the appendicectomy wound, probably as a result of initial appendicectomy at which the co-existent caecal neoplasm was missed. PMID- 2102214 TI - A case of infiltrating lipomatosis with diffuse, symmetrical distribution. AB - Infiltrating lipomatosis represents a distinct clinicopathological entity characterised by collections of non-encapsulated, mature lipocytes that infiltrate local tissues. The lesions are usually first observed during the first three decades of life, but congenital types exist. Although a predilection for the lower extremity exists in approximately 80% of patients, they can affect a multitude of anatomic sites. Infiltrating lipomatosis of the face, head and neck, upper and lower extremities, trunk and abdominal cavity and pelvis have all been reported. The patient presented here had symmetrical, diffuse infiltrating lipomatosis involving almost the whole body, sparing only the head, neck, fingers and toes. PMID- 2102215 TI - Bilateral, spontaneous, concurrent patellar tendon rupture. AB - Bilateral rupture of the infrapatellar tendon is extremely rare. When it occurs, it is almost always associated with connective tissue disease. We present a case of bilateral concurrent rupture of the patella tendon in a patient without any apparent systemic disease. PMID- 2102216 TI - Prolonged course of a cutaneous T-cell lymphoma with late systemic involvement. AB - The clinical course of cutaneous T-cell lymphomas is known to be extremely variable. The disease may be present for up to 50 years, although it has a median survival of four to ten years. Clinical manifestations may range from cutaneous involvement alone to widespread systemic involvement. Described here is a patient with an unusually prolonged course of a cutaneous T-cell lymphoma with systemic involvement which reappeared ten and 18 years after the initial presentation. The patient developed Sjogren's syndrome, bone marrow and peripheral nerve involvement late in the course of her disease. PMID- 2102217 TI - Idiopathic retroperitoneal haemorrhage. AB - Idiopathic retroperitoneal haemorrhage is a rare condition, affecting apparently histologically normal retroperitoneal blood vessels. It is important to search for the source of bleeding, as failure to identify the cause is associated with poor prognosis. PMID- 2102218 TI - Ovarian haemangioma. AB - Although ovaries have a very rich vasculature, haemangiomas of the ovary are extremely rare. There are only another 39 cases of ovarian haemangioma recorded in the literature. We describe an 11-year-old girl with an ovarian haemangioma who presented clinically with an acute abdomen. The patient has been well without complications for a year. PMID- 2102219 TI - Squamous cell carcinoma of the stomach following gastric surgery. AB - The development of adenocarcinoma in the gastric remnant following surgery for peptic ulceration is well recognised. However, squamous cell carcinoma of the stomach is rare, with only 80 cases being reported in the literature and none reported following gastric surgery. We report a case in which a squamous cell carcinoma with only minute areas of adenocarcinoma developed 22 years after surgery for a duodenal ulcer. PMID- 2102220 TI - A case of tumour simulating pulp space infection. AB - General practitioners and accident and emergency departments are often involved in the management of hand or finger sepsis. Such cases are usually easily diagnosed and treated. We report a more serious disorder which may mimic the condition and cause diagnostic confusion. PMID- 2102221 TI - Spontaneous rupture of liver due to cholangitis. AB - Spontaneous rupture of the liver is rare in the Western world and most cases are associated with primary or metastatic tumours. Spontaneous rupture of the intrahepatic biliary tree is not well documented and only two reports have been found in the literature. The authors describe a further case due to ascending cholangitis but presenting with biliary peritonitis. The literature is reviewed and the diagnostic problems discussed. PMID- 2102222 TI - Response to control of hyperthyroidism in patients with myasthenia gravis and thyrotoxicosis. AB - Three patients presenting with both myasthenia gravis and thyrotoxicosis were treated initially with pyridostigmine and carbimazole respectively. Control of the hyperthyroidism was achieved in all cases but was accompanied by deterioration of the myasthenic symptoms in two and persistence in one. Thymectomy was performed with subsequent improvement in all three patients. Histology showed thymic hyperplasia in each case. The relationship of myasthenia gravis, thyrotoxicosis and the thymus is discussed. PMID- 2102223 TI - Successful resuscitation and survival following massive overdose of metoprolol. AB - A 23-year-old female was found unconscious and deteriorated rapidly to cardiac asystole. Prolonged resuscitation was required, and she remained in severe cardiogenic shock, despite high doses of positive inotropic agents. Massive beta adrenoceptor blocker overdose was suspected (and subsequently confirmed). IV administration of glucagon was followed by prompt haemodynamic improvement and recovery, illustrating the beneficial role of glucagon in overwhelming beta adrenoceptor blockade. PMID- 2102224 TI - Full recovery following massive overdose with insulin and thyroxine. AB - Specific treatment is available for only a few substances taken in overdose. We report here a patient who attempted suicide with a massive overdose of insulin and thyroxine, a combination not previously reported, and discuss the specific treatments given to mitigate the harmful effects of this combination. PMID- 2102225 TI - Measles appendicitis. AB - Measles is a common disorder in the United Kingdom, due partly to the decreasing incidence of vaccination in children of a susceptible age. We report a case of abdominal pain in a child caused by the measles virus. PMID- 2102226 TI - The Convatec Wound Manager: a new stoma appliance. AB - Very occasionally, the surgeon must deal with a complicated abdominal wound which drains large volumes of fluid. One such situation arises when a postoperative enteric fistula occurs in association with a partial or complete dehiscence of a laparotomy wound. Another example occurs when the abdominal cavity is left open in the management of severe intra-abdominal sepsis. Both result in large abdominal wounds that are not satisfactorily contained by conventional dressings. Frequent changes of dressing are required and considerable skin excoriation and damage may occur. In addition, quantification of fluid output from a fistula may be grossly inaccurate. We wish to report the use of a new stoma appliance, the Convatec Wound Manager (Squibb Surgicare) which facilitates the management of these wounds. The case described illustrates many of the advantages of the appliance. PMID- 2102227 TI - Clostridial cholecystitis--the need for early recognition and treatment. AB - There remains some controversy regarding the timing of cholecystectomy after an attack of acute cholecystitis. Opinions vary between early operation within two and seven days and delayed operation readmitting the patient eight to twelve weeks later. There is, however, a small group of patients who require prompt emergency cholecystectomy. This group includes patients presenting with cholecystitis complicated by gas-forming organisms where the plain abdominal gas forming organisms where the plain abdominal radiograph can establish the diagnosis. PMID- 2102228 TI - Primary peritoneal sarcoma: three case reports and review of the literature. PMID- 2102229 TI - Thrombosed sapheno-varix: an important and unusual differential diagnosis of strangulated femoral hernia. AB - An incarcerated femoral hernia often requires prompt operative management to decrease the risk of bowel strangulation, perforation and death from peritonitis. We present a case of a 60-year-old man who had a clinically irreducible right femoral hernia, and in whom a Richter's hernia could not be excluded. He was found to have a thrombosed sapheno-varix with no evidence of a femoral hernia. Thrombosed sapheno-varix presenting as a strangulated femoral hernia has never previously been described in the literature. PMID- 2102230 TI - Successful control of atonic primary postpartum haemorrhage and prevention of hysterectomy, using i.v. prostaglandin E2. AB - Primary postpartum haemorrhage remains an important cause of maternal mortality and morbidity in England and Wales, despite the fact that avoidable causes can be identified in more than half the cases. The management of this potentially dangerous condition has been considered to be far from satisfactory. Conventional methods of management include the administration of oxytocin and ergometrine, and the use of bimanual compression. If these methods fail, surgical intervention, such as ligation of the hypogastric or internal iliac artery or even a hysterectomy, may be necessary. The full therapeutic potential of prostaglandin E2 in the management of atonic postpartum haemorrhage has not been widely recognised, even though it has been used successfully. We report one such case of atonic postpartum haemorrhage in which IV infusion of prostaglandin E2 was used with favourable results after conservative methods failed, thus avoiding a hysterectomy. PMID- 2102231 TI - Bilateral sensorineural hearing loss due to mumps. AB - Viral infections implicated in acute hearing loss include rubella, measles, mumps, herpes zoster, cytomegalovirus and influenza. Mumps' deafness is the best documented disorder. We describe a case where bilateral sensorineural hearing loss, following a severe mumps infection at the age of two, remained unnoticed until the age of four when the patient presented with delayed speech and language. This report emphasises the risk of permanent hearing loss as a complication of mumps infection and discusses strategies for early diagnosis and prevention. PMID- 2102232 TI - Iatrogenic gastrocolic fistula associated with non-steroidal anti-inflammatory drug administration. AB - An unusual case is presented of a benign gastrocolic fistula occurring in a 70 year-old man treated with piroxicam for arthritis for a period of only two months. This report illustrates that significant upper gastrointestinal complications can occur, even with short-term treatment, with non-steroidal anti inflammatory drugs (NSAIDs). PMID- 2102233 TI - Bacterial endocarditis of the tricuspid valve after insertion of a central venous catheter. AB - Central venous cannulation is a commonly used technique in the management of seriously ill patients. In experienced hands, the complication rate is low and primarily includes sepsis, thrombosis and local trauma. For chronic indwelling central venous catheters, thrombus formation within the right atrium has been described, particularly in premature infants, and a recent case has been reported in an adult. Valvular damage in the right heart is recognised and more often diagnosed at autopsy. This report describes the presence of tricuspid vegetations in a diabetic woman, related to the insertion of a central venous cannula. PMID- 2102234 TI - Pyogenic cervical vertebral osteomyelitis. AB - A 54-year-old male with cervical spine osteomyelitis due to haematogenous spread of staphylococcal infection from an intravenous cannula is reported. A review of literature is presented to illustrate the diagnostic difficulties and neurological complications of pyogenic vertebral osteomyelitis. PMID- 2102235 TI - Koebner's phenomenon and necrobiosis lipoidica diabeticorum. AB - In 1877, Dr Heinrich Koebner inflicted an experimental trauma on the uninvolved skin of a psoriatic patient. This resulted in the appearance of a typical psoriatic lesion at the site of trauma. This reaction, known as Koebner's phenomenon (KP), has subsequently been associated with several skin diseases. However, it has not been associated previously with necrobiosis lipoidica diabeticorum (NBL), a rare skin manifestation of diabetes mellitus. This report presents the unusual finding of NBL associated with KP in a patient with diabetes mellitus. PMID- 2102236 TI - Acalculous cholecystitis due to Salmonella virchow. AB - We report a case of systemic infection with Salmonella virchow in a 21-year-old male who subsequently developed acalculous cholecystitis. His symptoms and signs resolved with parenteral antibiotics, as did the ultrasonographic findings in the gall bladder. To our knowledge, this is the first reported case of acalculous cholecystitis due to this serotype. PMID- 2102237 TI - Pneumatosis intestinalis in AIDS: an unreported complication. AB - Pneumatosis intestinalis (PI) was first described by DuVernou in 1730. Since then, there have been reports of a benign form of PI occurring in both children and adults. Pneumatosis has been associated with a great many diseases, but to our knowledge there are no reports of pneumatosis in patients with acquired immune deficiency syndrome (AIDS). In this paper we report the incidental finding of PI in an AIDS patient. With ever-increasing numbers of AIDS patients, this entity may be seen more often, and clinicians should be aware of its clinical significance. PMID- 2102238 TI - An unusual irreducible clavicular fracture. PMID- 2102239 TI - Wernicke's encephalopathy in association with complicated acute pancreatitis and morbid obesity. AB - A young obese female with acute pancreatitis complicated by pseudocyst formation and intermittent gastric outlet obstruction, who had been maintained on high calorie enteral feeds, developed a sudden onset of confusion and ophthalmoplegia associated with papilloedema and retinal haemorrhages. A possible diagnosis of Wernicke's encephalopathy (WE) was made, and the patient was treated with parenteral thiamine. Clinical resolution was complete. Any patient with suspicious or unusual neurological symptoms and signs associated with possible malnutrition, hyperemesis or malabsorption should be given intravenous thiamine without delay to avoid the potential morbidity and mortality associated with undiagnosed WE. PMID- 2102240 TI - Simultaneous bilateral fractures of the femoral neck and superior pubis ramus following renal failure-induced hypocalcaemic convulsions. AB - There have only been a few reports of bilateral hip fractures resulting from hypocalcaemic convulsions. We report a case of simultaneous bilateral fractures of the femoral neck and superior pubic ramus caused by convulsions secondary to renal failure-induced hypocalcaemia. To our knowledge, such an occurrence has not previously been described. PMID- 2102241 TI - Acute hyponatraemia following total hip replacement. AB - An elderly woman who had been taking a fixed-dose combination of a thiazide and potassium-sparing diuretic for eight days, became severely hyponatraemic following total hip replacement. Her hyponatraemia resolved with fluid restriction, intravenous normal saline, and withdrawal of the drug. Hyponatraemia is a well-described side-effect of diuretic therapy; however, we are not aware of any previous reports of this condition developing acutely in the postoperative state. We attribute this to the natriuretic nature of the drug, compounded by the postoperative, anti-diuretic surge which itself may have been exacerbated by the drug. We thus advise caution in the use of this preparation in the elderly patient about to undergo major surgery. PMID- 2102242 TI - Severe post-coital puerperal vaginal tear. PMID- 2102243 TI - Rhabdomyolysis with renal dysfunction in a hypothermic man. AB - We describe a case of rhabdomyolysis with renal dysfunction in a 41-year-old previously healthy man with hypothermia. We believe this to be the first case of rhabdomyolysis and hypothermia so far described in the UK. PMID- 2102245 TI - An unusual pleural effusion. AB - Transudative pleural effusions usually result from systemic disorders such as congestive heart failure, hypoproteinaemic states and pneumonia. We report a patient who illustrates a rarely considered local mechanism of transudate formation. PMID- 2102244 TI - Gastrointestinal haemorrhage in a haemophiliac due to a jejunal haemangioma. AB - Spontaneous mucosal bleeding is not uncommon in hereditary coagulation factor deficiencies and is usually due to a local lesion. We report a case of repeated episodes of melaena in a known haemophiliac caused by a cavernous haemangioma in the jejunum. PMID- 2102246 TI - Acalculous cholecystitis complicating Legionnaires' disease. AB - Gastrointestinal complications of Legionnaires' disease are frequently reported. These include diarrhoea, paralytic ileus, acute appendicitis and jaundice. We would like to report the previously unrecorded and life-threatening complication of acalculous cholecystitis. PMID- 2102247 TI - Bilateral and recurrent obturator hernia. AB - Obturator hernia is a rare condition which was first described in 1722 by de Ronsil. It occurs most commonly in elderly women who have lost weight and may strangulate in 25-100% of cases. Strangulated obturator hernia has a mortality as high as 10-50%, which is partly due to delay in diagnosis. A patient who developed three obturator hernias is described. PMID- 2102248 TI - Loffler's eosinophilic endocarditis following carcinoma of the thyroid gland. PMID- 2102249 TI - Anal canal stenosis and pseudo-obstruction. AB - Mechanical large bowel obstruction and pseudo-obstruction can be difficult to differentiate because clinical symptoms and signs are often misleading. Although plain abdominal radiographs showing diffuse gaseous distension, no shut-off point and gas in the rectum are very suggestive of pseudo-obstruction, incomplete clinical examination with over-reliance on the abdominal radiographs may lead to large bowel mechanical obstruction being misdiagnosed as pseudo-obstruction. We report a rare case of large bowel obstruction occurring secondary to anal canal stenosis. PMID- 2102250 TI - Cystic hygroma of the breast in childhood. AB - Cystic hygromata are rare tumours of infancy. They usually occur at sites related to the embryological origins of the lymphatic system. A case is presented of a six-year-old boy with a cystic hygroma of the left breast. PMID- 2102251 TI - Pharyngeal croak--an unrecognised sign in allergic rhinitis in childhood. PMID- 2102252 TI - Recurrent spontaneous rupture of the urinary bladder. PMID- 2102253 TI - Control of metastatic Zollinger-Ellison syndrome with high-dose H2-receptor antagonists. PMID- 2102254 TI - Gilbert's syndrome unmasked as a cause of recurrent jaundice following porta caval shunt surgery. PMID- 2102255 TI - Third-degree heart block developing in an HLA-B27-positive individual with a family history of ankylosing spondylitis. AB - A case of complete heart block is presented in a patient whose brothers were known to have ankylosing spondylitis. Uveitis and sacro-iliitis are well recognised among HLA-B27-positive siblings of ankylosing spondylitis. However, heart block is a rare occurrence as a sole presentation in siblings of patients with ankylosing spondylitis. PMID- 2102256 TI - Liposarcoma of the spermatic cord. PMID- 2102257 TI - Pure motor monoparesis. PMID- 2102258 TI - Spontaneous perforation of a pyometrium: a complication of radiotherapy. PMID- 2102259 TI - A case of acute cholecystitis presenting as a strangulated femoral hernia. PMID- 2102260 TI - Analytical methodologies for the quantitation of platinum anti-cancer drugs and related compounds in biological media. AB - The methods for analysis of platinum-based anti-cancer drugs in biological media are reviewed in this paper. Although emphasis is placed on cisplatin, attention is also given to several of its analogues (carboplatin, iproplatin) and their degradation and biotransformation products. In an introductory section a short description is given of the historical background and the clinical applications of cisplatin. Reactions occurring in the body and in aqueous solutions are discussed because of their implications for the design of analytical procedures. After a detailed description of sample preparation and storage, attention is focussed on the analytical techniques used for the determination of either total platinum levels or individual platinum-containing compounds. The techniques discussed include atomic absorption and emission spectrometry, derivatization reactions and several chromatographic techniques with different detection methods. The specific advantages and disadvantages of these techniques are discussed. PMID- 2102261 TI - Application of photodiode array UV detection in the development of stability indicating LC methods: determination of mefenamic acid. PMID- 2102262 TI - High-performance liquid chromatographic determination of ambroxol in pharmaceuticals. PMID- 2102263 TI - Chemical ionization pyrolytical spectra of DNA. AB - The chemical ionization-pyrolytical (CI-Py) spectra of DNA and deuterated DNA (Herring Sperm) are recorded. The 200-800 a.m.u. region is examined for CH4, NH3, ND3, electron-capture and OH- CI spectra. The origin of major ion species is discussed. PMID- 2102264 TI - A polarographic study of the photodegradation of nitrendipine. AB - Nitrendipine produces a well-defined polarographic peak due to the four-electron reduction of the nitro group. This peak is used for tracking the photodecomposition of nitrendipine in both UV light and daylight conditions. The results show that nitrendipine remains unaltered in the short time scale of a normal analytical procedure and no special care with visible light exposure is necessary. However nitrendipine is strongly altered with UV irradiation showing a first-order degradation kinetics. A degradation rate constant of 0.0665 min-1 with a t1/2 of 10.423 min has been obtained. The UV degradation product was isolated and identified as the nitro pyridine analogue of nitrendipine. PMID- 2102265 TI - Determination of penicillin in pharmaceutical formulations by flow injection analysis using an optimised immobilised penicillinase reactor and iodometric detection. AB - An automated assay for the determination of penicillin in formulations suitable for use in pharmaceutical quality control is presented. The method is based on the classical iodometric penicillin assay which is incorporated in a flow injection analysis (FIA) system. The required hydrolysis is performed on-line by using an immobilised penicillinase reactor. Packed-bed and single-bead-string enzyme reactors are compared. It turns out that a packed-bed penicillinase reactor (10 cm x 1.5 mm i.d.) provides complete hydrolysis within short residence time, while only little back-pressure is generated. This enzyme reactor is stable for at least 9 months. Enzymatic hydrolysis of the beta-lactam ring results in the formation of the corresponding penicilloic acid, which consumes iodine. The iodine consumption is determined colorimetrically by measuring the decrease of the absorbance of the blue coloured iodine/starch complex. The optimum reactor length and flow rate for the colourimetrical detection reaction are determined. The optimised method is applied to the assay of penicillin in formulations and the results are compared with the "true" results obtained with a reference method: a mercurimetric titration. The reliability of the flow injection method is evaluated quantitatively by determining the maximum total error (MTE). The reliability is shown to be highest when measuring at a 0.3-mM level. Eight formulations including capsules, tablets and injectables containing penicillin G, amoxicillin or flucloxacillin are assayed. The MTE does not exceed the 6% level and the most probable MTE is between 1.5 and 3.5%. PMID- 2102266 TI - Dissolution studies on ampicillin embonate and amoxycillin embonate. AB - The dissolution behaviour of slightly water-soluble embonic acid salts of ampicillin and amoxycillin was studied quantitatively as a function of solution pH (1.15-8.00) using the rotating disk method combined with reversed-phase high performance liquid chromatography. The dissolution rate of ampicillin embonate was greater than that of amoxycillin embonate at all pH values investigated. The graphs of pH-intrinsic rate of dissolution of the antibiotics from the salts were U-shaped, the minimum being close to the respective isoelectric points of the parent antibiotics. Embonic acid was not detectable below pH 5; above pH 5 the dissolution rate of embonic acid increased as a function of pH. PMID- 2102267 TI - Fast-LC determination of 1-methyl-1H-tetrazole-5-thiol in human plasma with column-switching sample clean-up. AB - A simple, fast and sensitive method for the quantitative determination of 1 methyl-1H-tetrazole-5-thiol using HPLC is reported. Samples are deproteinated by plasma water filtration and injected into a HPLC system capable of column switching and backflushing the analytical column. The limit of quantitation was determined to be 70 ng ml-1 and the limit of detection 22 ng ml-1. Between-day precision (expressed as percent coefficient of variation) of standard curve slopes was +/- 3.5% with a range of within-day percent coefficient of variations from 0.28 to 1.4%. Recovery and precision of spiked control samples was 96 +/- 7% over a concentration range of 630-6300 ng ml-1. PMID- 2102268 TI - Detection of N-acetylcysteine, cysteine and their disulfides in urine by liquid chromatography with a dual-electrode amperometric detector. AB - A method for the determination of N-acetylcysteine, cysteine and their disulfides in urine is described. The thiols and disulfides are separated by reversed-phase ion-pair chromatography with octyl sodium sulfate as the ion-pairing reagent and detected with a dual-electrode amperometric detector using Au/Hg amalgam electrodes. Both the thiols and disulfides are detected with this system. In addition, dimers and mixed disulfides can be detected individually. PMID- 2102269 TI - 13C-NMR of Rauwolfia alkaloids. PMID- 2102271 TI - Cancer risks among nuclear submariners. PMID- 2102270 TI - Multicomponent analysis of hydrosoluble polyvitamins by first-derivative spectrophotometry. PMID- 2102272 TI - Breast cancer incidence and prevalence estimated from survival and mortality. AB - Survival probability for female breast cancer patients was used to estimate incidence rates from breast cancer mortality data in Italy. The female breast cancer survival curve from the Lombardy Cancer Registry (LCR) was used to test the method on data from four local cancer registries, covering areas in different regions of Italy. In spite of the well known geographic variability of female breast cancer incidence and mortality, the results support the idea that survival probability does not change across the country and that the survival probability from the LCR is a good estimate of that in the country as a whole. Female breast cancer incidence and prevalence rates were then estimated for Italy, making use of a mathematical model specifically developed for chronic diseases. In 1985, crude incidence and prevalence rates of female breast cancer, for ages up to 74 years, were estimated as 71 and 701 per 100,000 women, respectively. Estimated incidence rates show a complex trend with age, increasing to a temporary pronounced peak at the age of 52. A marked cohort effect was found to increase significantly the risk of the disease from the 1886 to the 1930 birth cohorts by a factor of 2.9. After the 1930 cohort, risks have continued at a constant high level. PMID- 2102273 TI - Cancer causes and control. PMID- 2102274 TI - Smoking and breast cancer risk in Denmark. AB - The effect of smoking on breast cancer risk was evaluated in a population-based case-control study, including 1,480 women diagnosed with breast cancer in Denmark between 1983-84. They were identified from the files of the nationwide clinical trial of the Danish Breast Cancer Cooperative Group and the Danish Cancer Registry. The control group was an age-stratified sample of 1,332 women from the general population. Data on risk factors were collected by self-administered questionnaires. The risk of breast cancer among current smokers and ex-smokers was similar to that in non-smokers, both risk estimates being close to unity. No dose-response relation was observed for any measure of smoking (age at start, duration, number of cigarettes per day, or cigarette-years of exposure) in all subjects, and when pre- and post-menopausal women were examined separately. These findings suggest that smoking is not associated with the risk of breast cancer. PMID- 2102275 TI - Incidence of cancer of the lung, stomach, breast, and cervix in the USSR: pattern and trends. AB - The most frequent fatal malignant tumors in the Soviet Union are cancers of the lung, stomach, breast, and cervix uteri. From incidence statistics and population estimates provided by the Department of Statistics of the Ministry of Health, age adjusted incidence rates for the period 1971-87, using the World standard population, have been computed for the USSR as a whole and for each of the 15 Soviet republics. For six republics believed to have the highest quality of data and relatively homogeneous populations, time-trends are examined over the period. There is important geographical variation in the incidence of malignant tumors in the Soviet Union. The differences between high and low incidence areas are four fold for cancer of the lung and stomach, three-fold for cancer of the breast and two-fold for cancer of the cervix. Overall in the six republics for which time trends are examined, cancers of the lung and breast have increased, cancers of the stomach and cervix have decreased. There are some variations in specific age groups in some republics. PMID- 2102276 TI - A case-control study of alcoholic beverage consumption in relation to risk of cancer of the right colon and rectum in men. AB - To examine the relation between alcoholic beverage consumption and risk of cancer of the right colon and rectum, 644 male cases and 992 male community controls were interviewed by telephone. The risks of cancer at these sites associated with alcohol consumption five years in the past were similar; using subjects with right colon cancer for reference, the adjusted relative risk (RR) of rectal cancer associated with five or more drinks per day was 0.9 (95% confidence limits = 0.4, 1.7). Alcohol consumption 20 years in the past was associated with a greater risk of rectal cancer (RR for five or more drinks per day = 1.8 [1.0, 3.3]). Analyses based on a community controls provided weaker evidence, consistent with previous findings, that heavy consumption of alcohol five years in the past, and possibly of beer in particular, was associated with moderately increased risk of colorectal cancer (RR of cancer of the right colon associated with consumption of five or more alcoholic drinks per day was 1.8 [1.0, 3.2], and of cancer of the rectum was 1.5 [0.9, 2.5]). PMID- 2102277 TI - Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles: results from two breast cancer case-control studies. AB - To assess whether risk of breast cancer in young women is associated with differences in luteal-phase hormone production and to attempt to explain differences in risk of breast cancer of young Shanghai Chinese and Los Angeles white women, two concurrent case-control studies of serum hormone concentrations were conducted. Both studies were carefully controlled for the possible confounding effects of age, weight, height, pregnancy history, and day of the menstrual cycle, by individually matching cases and controls on these factors. Case eligibility was limited to women with localized breast cancer. Sixteen of 39 Shanghai breast-cancer cases were sampled prior to the histologic diagnosis of their disease. The remaining 23 Shanghai cases and all 42 Los Angeles cases were diagnosed, and treated by surgery only, at least six months prior to hormonal evaluation. All subjects were sampled on day 22 of the menstrual cycle. Overall, cases had 13.5% higher serum estradiol concentrations (p = 0.038) with a case-to control excess of 16.6% in Shanghai subjects (p = 0.089) and 10.8% in Los Angeles subjects (p = 0.23). There were no appreciable differences in amounts of sex hormone binding globulin between cases and controls. Cases had lower progesterone levels than controls, but the situation was reversed when the analysis was restricted to subjects with evidence of ovulation. Los Angeles controls had 20.6% greater estradiol concentrations than Shanghai controls (p = 0.036); adjustment for body weight accounted for only 25.7% of this difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102278 TI - Type of cigarettes and cancers of the upper digestive and respiratory tract. AB - The relationship between type of cigarettes smoked and the risk of cancer of upper digestive and respiratory sites was investigated in a case-control study conducted in Northern Italy on 291 males with cancer of the oral cavity or pharynx, 288 with cancer of the esophagus, 162 with cancer of the larynx, and 1,272 control subjects in hospital for acute conditions unrelated to tobacco or alcohol consumption. Using a distinction based on tar-yield or the brand smoked for the longest time (less than 22 mg, low to medium tar; greater than or equal to 22 mg, high tar), the multivariate relative risks among ever-smokers were 8.5 for low/medium and 16.4 for high tar cigarettes for oral and pharyngeal neoplasms, 3.3 and 7.8 for esophageal, and 4.8 and 7.1 for laryngeal cancers. The differences according to type of cigarettes were similar in proportional terms, and hence larger in absolute terms, when analysis was restricted to current smokers only. Thus, these data provide further quantitative evidence on the importance of type of cigarette smoked on the risk of upper-digestive and respiratory tract cancers and have important public health implications. PMID- 2102279 TI - Childhood brain tumor: presentation at younger age is associated with a family tumor history. AB - In a registry-based sample of 361 children with a brain tumor, those whose grandparents and great-grandparents had a history of any kind of tumor were younger at the time of presentation than were those who lacked this family history (p = 0.1). In post hoc analyses, the age difference was most apparent among children with cerebral tumors, and when family history was limited to brain tumors and to great-grandparents. These findings are in keeping with the hypothesis that a familial tumor diathesis contributes to an early age at onset of a brain tumor in some children. PMID- 2102281 TI - Maternal age, parity, and pregnancy estrogens. AB - Total estrogens (TE), estradiol (E2), estriol (E3), and human placental lactogen (hPL) were determined by radioimmunoassay in the blood of 126 pregnant women during their 26th and 31st weeks of pregnancy and the results were studied in relation to maternal age and parity. Total estrogens and E2 were lowest among the youngest women (less than 20 years) and highest among women aged 20-24 years, whereas older women (25+ years) had, on the average, intermediate values. For E3 the pattern was qualitatively similar to that of TE and E2 but less striking, and no maternal age pattern was evident with respect to hPL. Within maternal age groups, TE and E2 were higher among women in the first, than among those in their second, full-term pregnancy; the difference was about seven percent for TE (P = 0.14) and about 14 percent for E2 (P = 0.05). No parity patterns were evident with respect to E3 and hPL. There were fairly strong correlations between the determinations of the same hormone in the same woman during the 26th and 31st weeks of pregnancy; Pearson correlation coefficients were 0.60 for TE, 0.78 for E2, 0.60 for E3, and 0.72 for hPL. Since the risk of breast cancer increases apparently monotonically with maternal age at birth, the present data are equivocal with respect to the hypothesis linking levels of pregnancy estrogens to risk of breast cancer in the offspring. However, the data are compatible with hypotheses linking excessive pregnancy-estrogen exposure to conditions more common among first-born individuals, including testicular cancer and cryptorchidism. PMID- 2102280 TI - Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption. AB - International variations and national time trends in disease rates suggest major associations between dietary fat and several important cancers. In contrast, case control and cohort studies of dietary fat in relation to the same cancers generally report weak associations, or have failed to detect any association with fat intake. This study was undertaken in an attempt to understand the apparent discrepancy between these observations. The results provide an insight into the magnitude of cancer risk reduction that may follow from a practical reduction in dietary fat. Regression analyses of international variations in cancer incidence rates were used to estimate relative risks (RR) as a function of fat intakes for both males and females. These analyses focused on cancers of the breast, colon, rectum, ovary, and endometrium in females, and colon, rectum, and prostate cancers in males. Ages 55-69 and 30-44 were considered in order to compare RR estimates between an older and younger age group, and between post- and pre menopausal women. Corresponding RR estimates were also calculated, based on the regression of changes in disease rates from the mid-1960s to 1980 on changes in dietary fat, using data from several countries. A strong degree of consistency with the RR estimates from international comparisons was observed. The international regression analyses were also used to project changes in cancer rates among Japanese migrants to the United States. A high level of consistency with the observed disease-rate changes was noted. Similarly, the international data analyses were used to project RRs for the fat intake categories used in specific case-control and cohort studies, while acknowledging measurement error in individual dietary assessment. Although certain exceptions are noted, considerable consistency was found between the aggregate and analytic data results, leaving open the strong possibility that a practical reduction in dietary fat could result in a major reduction in the incidence of several prominent cancers in the United States and in other nations having high fat consumption. PMID- 2102282 TI - A case-control study of risk factor for renal cell cancer in northern Italy. AB - A hospital-based case-control study of renal cell cancer was conducted in northern Italy between 1986 and 1989, with 240 cases of renal cell cancer (150 males and 90 females), and 665 controls (445 males and 220 females) chosen on the basis of age, sex, and area of residence. No associations were found between renal cell cancer and: body mass index (BMI); number of cigarettes smoked; age at starting to smoke; years of smoking; consumption of wine, beer, spirits, coffee, decaffeinated coffee; tea; intake of animal protein, fruits, and vegetables; various reproductive factors; hormonal use; sexual habits; sexually transmitted diseases; or selected occupational exposures. The odds ratio (OR) was above unity in smokers (OR = 1.34 for greater than or equal to 15 cigarettes/day), but the trends in risk with dose or duration were not statistically significant. Significant positive associations were found between renal cell cancer and sources of fat intake, especially margarine (OR for highest vs lowest intake = 1.71), and oils (OR = 1.89) whereas carrot intake showed a negative association (OR = 0.62). Also, a history of nephrolithiasis and multiple episodes of cystitis showed weak positive associations (OR = 2.00, 95 percent confidence interval (CI) 1.07-3.73; and OR = 1.60, 95 percent CI 0.95-2.70, respectively). PMID- 2102283 TI - Comparison of the descriptive epidemiology of urinary tract cancers. AB - We compared the descriptive epidemiology of several urinary tract cancers, utilizing incidence data from the United States and international sources. The patterns of cancers of the renal pelvis, ureter, and urethra were more similar to those of bladder cancer than to cancer of the renal parenchyma in several ways: (i) transitional cell carcinoma is the predominant histologic type in the renal pelvis, ureter, urethra, and bladder, whereas the vast majority of renal parenchyma neoplasms are adenocarcinomas; (ii) in situ tumors often appear in all these sites except the renal parenchyma; (iii) rate ratios for renal pelvis/ureter cancers among blacks and Hispanics, relative to whites, are closer to those for bladder than to those for renal parenchymal cancers; (iv) rates among US men and women for cancers of the renal pelvis and ureter are more highly correlated with those for bladder cancer than with those of the renal parenchyma across racial groups; and (v) similar correlations occur among women across geographic areas within the US and internationally. However, the patterns for cancers of the renal pelvis and ureter do not always resemble more closely those for bladder than renal parenchyma cancers and occasionally appear different from one another. These findings indicate the importance of distinguishing tumors based on specific primary site and cell type. PMID- 2102284 TI - Risk of subsequent cytological abnormality and cancer among women with a history of cervical intraepithelial neoplasia: a comparative study. AB - A longitudinal study of 1,281 women with a histological diagnosis of cervical intraepithelial neoplasia (CIN) during 1974-76 is presented. After 12 years of follow-up, 30 percent of the women had further cytological abnormalities reported. The rate of subsequent abnormality was highest during the first 12 months of follow-up; thereafter, there was no evidence of any decline in the rate of subsequent abnormality with increasing duration of follow-up. Women from the CIN cohort had twice as many later cytological abnormalities as an age-matched cohort of women who were negatively screened during 1974-76 (excluding abnormalities within 12 months of entry to the study and after adjustment for smear frequency). The CIN cohort remained at substantially greater risk for a subsequent diagnosis of squamous cell carcinoma of the cervix compared with the control group of negatively-screened women (rate ratio 19.8, 95 percent confidence interval 2.4-163.6, P less than 0.01). These results indicate that women who have received surgical intervention for CIN continue to have substantial morbidity from cervical abnormalities during medium-term follow-up. PMID- 2102285 TI - Diet and age at menarche. AB - Early menarche has been associated with higher risk of breast cancer. A prospective study has been conducted in Quebec City, Canada, to evaluate the relationship of dietary intake to age at menarche. On three occasions during the schoolyear 1986-87, 2,299 pre-menarche. Incidence density ratios (IDRs) adjusted for age at entry and mothers' age at menarche were computed using proportional hazards models. IDRs for quartiles of energy, nutrient and food-group intakes were not different from the null value. In this population of well-nourished girls, diet did not influence the age at onset of menarche. PMID- 2102286 TI - Exposure-response relationships between woodworking, smoking or passive smoking, and squamous cell neoplasms of the maxillary sinus. AB - A case-control study of squamous cell neoplasms of the maxillary sinus was performed in Hokkaido during 1982-86, with 169 cases and 338 controls matched for sex, age, and residence. The data were analyzed by a stepwise forward-selection method based on a conditional logistic-regression model without interaction terms, log-likelihood ratio tests, and chi-square tests for trend. Statistically significant linear trends were observed for associations between the risk of squamous-cell maxillary-sinus neoplasms and the duration of woodworking among men, the daily or lifetime amount of smoking among men, and the number of smokers in the household as an index of domestic exposure to cigarette smoke among women. PMID- 2102287 TI - Anthropometric measures and breast cancer in young women. AB - Body height and weight in relation to breast cancer in women younger than 45 years were investigated in a case-control study in Sweden and Norway. The study included 317 Swedish and 105 Norwegian cases diagnosed in 1984-85 with 317 Swedish and 210 Norwegian age-matched population controls. Neither height nor body size, measured as body mass index, was associated with breast cancer. Change in body mass from the age of 20 years to 18 months before the time of diagnosis (cases) or interview (controls) had no effect on breast cancer risk. The study provides no evidence that anthropometric measures are risk factors for breast cancer in young women, indicating that the postulated inverse relationship between body mass index and pre-menopausal breast cancer could be limited to peri menopausal women. PMID- 2102288 TI - Tobacco smoking, alcohol consumption, and risk of oral cancer: a case-control study in Beijing, People's Republic of China. AB - A case-control study of oral cancer was conducted in Beijing, People's Republic of China (PRC). The study was hospital-based and controls were hospital in patients matched for age and gender with the cases. The response rates for cases and controls were 100 percent and 404 case/control pairs were interviewed. Tobacco smoking and alcohol consumption emerged as independent risk factors for oral cancer. For tobacco smoking, the association was considerably stronger for smokers of pipes than for smokers of cigarettes. For all kinds of tobacco, expressed as cigarette equivalents, the odds ratio (OR) for total pack-years smoked, among males, rose from 1.0 in never-smokers to 3.7 (95 percent confidence interval, 1.8-7.4) in the highest quintile of exposure. Similar results were found for females. The association with tobacco consumption was strong for squamous cell carcinoma but there was no trend in risk associated with tobacco for adenocarcinomas and other histologic types. So few women reported consuming alcohol that this variable could be examined only in males. Risk in the highest category of total lifetime intake of alcohol relative to that in lifetime abstainers was 2.3 (1.1-4.8) with a significant trend in risk with increasing dose (P less than 0.002). The combined effects of tobacco and alcohol appear to be approximately multiplicative in males. The attributable risk of oral cancer for tobacco among tobacco smokers was estimated as 34 percent (45 percent among males and 21 percent among females); for alcohol consumption in males the estimate was 23 percent. PMID- 2102289 TI - Changing mortality from esophageal cancer in males in Denmark and other European countries, in relation to changing levels of alcohol consumption. AB - Age-specific mortality rates from esophageal cancer in men are considered by year of birth in European countries with different levels of alcohol consumption. In countries with high and increasing levels of alcohol consumption (Denmark, Hungary, Federal Republic of Germany, and Czechoslovakia) successive birth cohorts born after about 1910 experience increasing mortality from esophageal cancer in all age-groups. No clear trend in esophageal cancer mortality was observed in countries starting from lower levels of alcohol consumption, even in the presence of increasing consumption (Sweden, Norway, Finland, Netherlands, Poland, UK). There was an apparent threshold around 8 l of ethanol per capita per year. Likewise, no upward trend in esophageal cancer mortality was observed in countries with high and stable alcohol consumption (France, Italy, Portugal). These findings are in agreement with results of analytic epidemiologic studies which indicate that esophageal cancer mortality is only slightly affected by moderate doses of alcohol, but rises steeply with consumption of large quantities. The incidence and mortality of esophageal cancer is likely to increase further in the future in countries where the level of alcohol consumption was relatively high in 1960 and where consumption increased further in the 1960s and 1970s. PMID- 2102290 TI - Cancer incidence rates among Japanese immigrants in the city of Sao Paulo, Brazil, 1969-78. AB - Cancer incidence rates among first-generation Japanese immigrants in the city of Sao Paulo, Brazil, were estimated from the data of the Sao Paulo Cancer Registry during the years 1969 to 1978. From all registered cases, 2,179 cancer cases of Japan-born residents (1,288 males, 891 females) were selected and age-specific and summary age-adjusted incidence rates (AAIR) were calculated for the selected sites of cancer. The AAIR for all sites except non-melanoma skin cancer was 195.2 per 100,000 population (95 percent confidence interval: 176.4-214.1) in males and 147.3 (134.6-160.0) in females. Stomach cancer had the highest incidence rate of all cancers in both sexes (males, 69.3; females, 32.0). This was followed by cancer of the lung (22.5), esophagus (10.2), colon (8.3), and prostate (7.1) in males; and by breast (24.0), cervix (18.0), colon (8.4), and lung (7.2) in females. When these rates were compared with those among Japanese in Japan, cancer of the stomach and rectum revealed significantly lower rates, while non melanoma skin cancer, and prostate and breast cancer showed higher rates. No significant increase of colorectal cancer was recognized among Japanese immigrants in Sao Paulo, contrary to the remarkably high rates of colorectal cancer being observed among Japanese immigrants in the US. PMID- 2102291 TI - Leukemia and cigarette smoking. PMID- 2102292 TI - Trends in endometrial cancer incidence and mortality in Sweden, 1960-84. AB - Trends in incidence of and mortality from invasive endometrial cancer in Sweden in 1960-84 were analyzed. The study was based on virtually all 20,371 patients given this diagnosis and 4,887 patients who died of the disease in that period. Only minor changes occurred in age-standardized incidence in pre-menopausal women, in whom the rates declined consistently during the last 15 years, especially in the youngest age groups. Among post-menopausal women, an early increase was followed by stable rates in women over 60 and decreasing rates at ages 50-59 years. In contrast, mortality rates decreased consistently over the study period. Multivariate regression analyses indicated that birth cohort was a more important determinant of incidence and mortality than was time period. The relative risk of developing endometrial cancer increased by about 20 percent in women born around 1900 as compared with 1880, and by an additional 40 percent from the 1910 cohort to the maximum risk attained in those born around 1930. In successively younger birth cohorts, the risk markedly and continuously declined. These strong birth-cohort effects after 1910 may be reasonably explained by the change from the risk-increasing estrogen-only replacement therapy introduced in the 1960s to the less harmful use, starting about 10 years later, of combined estrogen-progestogen regimens; and further, by the protective exposure of a large proportion of pre-menopausal women to oral contraceptives. Mortality, however, decreased steadily in successive cohorts from those born in 1890, indicating that the increase in incidence was referable mainly to non-lethal cancers. PMID- 2102293 TI - Occupational risk factors for brain tumors: results from a population-based case control study in Germany. AB - In a population-based case-control study in the Rhein-Neckar-Odenwald area (containing 1.3 million inhabitants) of the Federal Republic of Germany (FRG), risk factors were assessed for brain tumor development in 226 cases with primary brain tumors (ICD-9 191, 192.1, 192.0) and 418 population controls, interviewed by a standardized questionnaire. The analysis of occupational risk factors and smoking is presented. No elevated risk was found for smoking. Similarly, no significant effects were found for most occupations. Five specific occupational groups were examined because of a priori determination that they were of interest. Some categories showed slightly elevated risks but in none was the elevation statistically significant. A significant increase in risk for brain tumor development was found associated with working in electrical occupations for women (relative risk [RR] = 5.2; 95 percent confidence interval [CI] 1.4-20.1) but not for men (RR = 0.9, 95 percent CI 0.3-2.3). PMID- 2102294 TI - Cigarette smoking and liver cancer among US veterans. AB - The relationship of tobacco use with risk of primary liver cancer was investigated using data from a 26-year mortality follow-up of nearly 250,000 US veterans, mostly from World War I. Significantly increased risks for liver cancer (289 deaths) were associated with most forms of tobacco use, including pipe and cigar smoking. Elevated relative risks (RRs) were seen for current cigarette smokers (RR = 2.4; 95 percent confidence interval [CI] 1.6-3.5) and former cigarette smokers (RR = 1.9, 1.2-2.9). A strong dose-response relationship (P less than 0.001) was found for cigarette smoking, with smokers of 40 or more cigarettes per day having almost a fourfold risk (RR = 3.8, 1.9-8.0). Risks were also found to increase significantly with years of cigarette use and with earlier age at the start of cigarette smoking. These results are consistent with those of other cohort and case-control studies, suggesting that cigarette smoking may be related to the risk of liver cancer. PMID- 2102295 TI - An epidemiologic study of thyroid cancer in Hawaii. AB - A population-based case-control interview study was designed to test the hypothesis that dietary iodine or the consumption of goitrogenic vegetables increases the risk of thyroid cancer. A total of 191 histologically confirmed cases (64 percent female) and 441 matched controls from five ethnic groups in Hawaii were available for analysis. Among women, intake of seafood (especially shellfish), harm ha (a fermented fish sauce), and dietary iodine were associated with an increased risk of cancer, whereas consumption of goitrogenic (primarily cruciferous) vegetables was associated with a decreased risk. Non-dietary risk factors included miscarriage (especially at first pregnancy), use of fertility drugs, family history of thyroid disease, obesity, and work as a farm laborer. The odds ratio for the combined effect of a high iodine intake and a first pregnancy miscarriage was 4.8 (95 percent confidence interval [CI] = 1.2-19.2); and for high iodine intake and use of fertility drugs 7.3 (95 percent CI = 1.5 34.5). Among men, positive associations were found for obesity, work as a farm laborer, and a past history of benign thyroid disease. Although this study identified several dietary and non-dietary risk factors for thyroid cancer, it could not fully explain the exceptionally high incidence rates among Filipino women in Hawaii. PMID- 2102296 TI - Dentition, oral hygiene, and risk of oral cancer: a case-control study in Beijing, People's Republic of China. AB - A case-control study of oral cancer was conducted in Beijing, People's Republic of China. The study was hospital-based and controls were hospital in-patients matched to the cases by age and gender. A total of 404 case/control pairs were interviewed. This paper provides data regarding oral conditions as risk factors for oral cancer, with every patient having an intact mouth examined (pre operation among cases) using a standard examination completed by trained oral physicians. After adjustment for tobacco smoking and alcohol consumption, poor dentition--as reflected by missing teeth--emerged as a strong risk factor for oral cancer: the odds ratio (OR) for those who had lost 15-32 teeth compared to those who had lost none was 5.3 for men and 7.3 for women and the trend was significant (P less than 0.01) in both genders. Those who reported that they did not brush their teeth also had an elevated risk (OR = 6.9 for men, 2.5 for women). Compared to those who had no oral mucosal lesions on examination (OR = 1.0), persons with leukoplakia and lichen planus also showed an elevated risk of oral cancer among men and women. Denture wearing per se did not increase oral cancer risk (OR = 1.0 for men, 1.3 for women) although wearing metal dentures augmented risk (OR = 5.5 for men). These findings indicate that oral hygiene and several oral conditions are risk factors for oral cancer, independently of the known risks associated with smoking and drinking. PMID- 2102298 TI - Gynecologic oncology. PMID- 2102297 TI - Exposure of nonsmoking women to environmental tobacco smoke: a 10-country collaborative study. AB - The interpretation and interpretability of epidemiologic studies of environmental tobacco smoke (ETS) depend largely on the validity of self-reported exposure. To investigate to what extent questionnaires can indicate exposure levels to ETS, an international study was conducted in 13 centers located in 10 countries, and 1,369 nonsmoking women were interviewed. The present paper describes the results of the analysis of self-reported recent exposure to ETS from any source in relation to urinary concentrations of cotinine. Of the total, 19.7 percent of the subjects had nondetectable cotinine levels, the median value was 6 ng/mg, and the cut-point of the highest decile was 24 ng/mg. The proportion of subjects misreporting their active smoking habit was estimated at between 1.9 and 3.4 percent, depending on whether cut-points of 50 or 100 ng/mg creatinine were used. Large and statistically significant differences were observed between centers, with the lowest values in Honolulu, Shanghai, and Chandigarh, and the highest in Trieste, Los Angeles, and Athens. Mean cotinine/creatinine levels showed a clear linear increase from the group of women not exposed either at home or at work, to the group of those exposed both at home and at work. Values were significantly higher for women exposed to ETS from the husband but not at work, than for those exposed at work but not from the husband. The results of linear regression analysis indicated that duration of exposure and number of cigarettes to which the subject reported being exposed were strongly related to urinary cotinine. ETS exposure from the husband was best measured by the number of cigarettes, while exposure at work was more strongly related to duration of exposure. After adjustment of number of cigarettes for volume of indoor places, a similar increase in cotinine (5 ng/mg) was predicted by the exposure to 7.2 cigarettes/8 h/40 m3 from the husband and 17.9 cigarettes/8 h/40 m3 at work. The results indicate that, when appropriately questioned, nonsmoking women can provide a reasonably accurate description of ETS exposure. Assessment of individual exposure to ETS should focus on daily duration and volume of indoor places where exposure occurred. PMID- 2102299 TI - Medical disorders in pregnancy, including hypertensive diseases. PMID- 2102300 TI - The puerperium, breastfeeding, and breast milk. PMID- 2102301 TI - Induction of labor, complications of labor, and postmaturity. PMID- 2102302 TI - Epidemiology, antenatal screening, nutrition, and therapeutics in pregnancy. PMID- 2102303 TI - Maternal, fetal, and neonatal physiology in pregnancy. PMID- 2102304 TI - Multiple pregnancy, operative delivery, anesthesia, and analgesia. PMID- 2102305 TI - Detection of breast cancer. PMID- 2102306 TI - Tumor markers in ovarian carcinoma. PMID- 2102307 TI - Secondary surgery for epithelial ovarian cancer. PMID- 2102308 TI - Role of radiation therapy in ovarian cancer. PMID- 2102309 TI - Hormonal aspects of endometrial cancer. AB - In summary, endometrial cancer is an estrogen-related neoplasm whose precursor lesion, endometrial hyperplasia, may be successfully treated with progestational agents. Trials of adjunctive progestin therapy have failed to demonstrate benefit, even though the malignancy is sensitive to palliative therapy with progestins as well as tamoxifen. Paradoxically, chronic tamoxifen exposure in postmenopausal women may increase the risk of endometrial cancer, and such women must be followed closely. Progesterone receptor may be measured using competitive binding assays or by immunohistochemical techniques. There is tumor heterogeneity with regard to progesterone receptor. Tissues surrounding the cancer may contain progesterone receptor and produce false-positive results in biochemical assays. Last, the presence of progesterone receptor not only predicts responsiveness to progestational therapy, but also confers a survival advantage in patients with endometrial cancer. PMID- 2102310 TI - Pitfalls in the screening and early diagnosis of cervical cancer. PMID- 2102311 TI - Preterm labor, preterm delivery, intrauterine infection, and preterm rupture of membranes. PMID- 2102312 TI - Multimodality therapy in advanced cervical carcinoma. PMID- 2102313 TI - Maternal/fetal medicine. PMID- 2102314 TI - Epidemiology of infertility. PMID- 2102315 TI - Corpus luteum defects. PMID- 2102316 TI - Cervical factors in infertility. PMID- 2102317 TI - Surgical management of tubal factor infertility. PMID- 2102318 TI - New approaches to treatment of male infertility. PMID- 2102319 TI - Fetal anomalies. PMID- 2102320 TI - Structural heart disease. PMID- 2102321 TI - Teratogenesis: alcohol, angiotensin-converting-enzyme inhibitors, and cocaine. PMID- 2102322 TI - Fetal surveillance. PMID- 2102323 TI - Chorionic villus sampling and amniocentesis. PMID- 2102324 TI - General, regional, and local anesthesia. PMID- 2102325 TI - Abdominal, vaginal, and laser surgery. PMID- 2102326 TI - Contraception. PMID- 2102327 TI - Malignant disease. PMID- 2102328 TI - Fertility and infertility. PMID- 2102330 TI - Gynecologic surgery. PMID- 2102329 TI - Prenatal diagnosis. PMID- 2102331 TI - Polycystic ovarian disease. PMID- 2102332 TI - Hyperprolactinemia and the management of related tumors. PMID- 2102333 TI - Management of amenorrhea and associated disorders. PMID- 2102334 TI - Ovarian failure including menopause, premature menopause, and resistant ovarian syndrome, and hormonal replacement. PMID- 2102335 TI - Ovulatory disorders and infertility in women with regular menstrual cycles. PMID- 2102336 TI - Endocrinology of male fertility and infertility. PMID- 2102337 TI - Benign pathology of the ovary. PMID- 2102338 TI - Pathology of malignant ovarian tumors. PMID- 2102339 TI - Pathology of the uterine body. PMID- 2102340 TI - Pathology of the fallopian tube and vagina. PMID- 2102341 TI - Benign pathology of the breast. PMID- 2102342 TI - Malignant pathology of the breast. PMID- 2102343 TI - Reproductive endocrinology. PMID- 2102344 TI - Gynecologic pathology. PMID- 2102346 TI - Cell content of cervical smears. PMID- 2102345 TI - Immunogold labelling of tumour cells during NK/target cell interactions. AB - Using a system of immunocolloidal gold labelling, we have monitored the expression and distribution of transferrin receptors (TfRs) within the K562 cell line, during NK/target cell interactions. An indirect method of immunolabelling was used to effectively immunolabel tumour cells without disrupting the natural effector:target interactions. Successful localization of TfRs demonstrates the potential of the described technique for discerning antigenic distribution of other cell:cell interactions. Immunolabelling has also provided a useful method for demonstrating receptor down-regulation within NK target cells, as a proposed cause of reduced receptor expression by TPA-treated cells. Following 30 and 60 min incubation periods with TPA, approximately 15 and 30%, respectively, of the gold/antibody complexes were relocated from the surface membrane to an intracellular location within endocytotic vesicles. The demonstration of receptor down-regulation is important as a proposed cause of TPA-induced tumour cell resistance to NK-mediated cytolysis. PMID- 2102347 TI - Fine needle aspiration. PMID- 2102348 TI - Cervical screening performance in general practice. An evaluation in a single health district. AB - This paper describes a study of cervical screening in 50 general practices in the East Berkshire Health District over a period of 2 1/2 years. Six practices organized their own practice based screening scheme. Thirty-nine participated in a district organized scheme and five did not actively participate in any scheme. The proportion of women screened was highest among the practices which organized their own scheme. These practices were large, in non-urban locations and employed a practice nurse. In contrast, practices which had a poor record of screening were small, single handed, in an urban location and were unwilling to participate in a district call scheme or organize their own scheme. It is recommended that the practices which are prepared to organize their own screening programmes should be encouraged to do so. The resources which are saved could then be more usefully spent on providing assistance to the practices which do not offer a cervical screening service to women on their practice lists. PMID- 2102349 TI - Audit of fine needle aspiration cytology of 120 renal lesions. AB - Solid renal masses in 120 patients were assessed by percutaneous fine needle aspiration cytology, performed under radiographic guidance. Follow-up was obtained in all but seven cases. Diagnostic sensitivity for 83 tumours in the series was 91.6%, while two false positive reports resulted in a specificity of 93.8%. Positive and negative predictive values were 97.4% and 81.1% respectively. One advantage of the procedure was the ability to cell type neoplasms accurately, which enabled administration of pre-operative chemotherapy in childhood tumours, and selection of appropriate surgical procedures in adults. The technique offered a non-surgical means of confirming primary renal tumours in patients presenting initially with distant metastases, and documenting renal secondaries in cases with malignancy at other sites. The diagnosis of benign or inflammatory lesions permitted institution of definitive therapy. PMID- 2102350 TI - Cytology of colorectal adenomas. AB - A study of the cytological appearances of benign and malignant colorectal adenomatous polyps is reported. The aim of the study was to characterize the cytological features of adenomatous polyps and predict the likelihood of malignancy using cytology. A five grade classification of colorectal cytology has been developed and the characteristic appearances of cells from adenomatous polyps are described. The reproducibility of cytological diagnosis based on this classification has been tested in 120 smears from normal mucosa and adenomatous polyps (including polyp cancers). Correlation with histology was achieved in 88% and correlation of the cytological diagnosis between two observers was achieved in 84%. We conclude that cytology can be used reliably as an adjunct to histology in the assessment of malignancy of adenomatous polyps. PMID- 2102351 TI - Evaluation of fine needle aspiration of the male breast for the diagnosis of gynaecomastia. AB - Fine needle aspiration of the male breast can present problems of diagnosis because the cytological presentation of gynaecomastia can be confused with that of adenocarcinoma. We reviewed breast aspirates from 24 male patients in order to determine the accuracy of cytology as a method of diagnosing gynaecomastia. Discrepancies were observed between the original cytology reports on one hand and the review cytology and biopsies on the other. Of the 24 aspirates from the male breast, the cytology was reported as negative in 16 cases, suspicious in three cases and malignant in five. In four cases of the negative group, a specific diagnosis of gynaecomastia was made. In two of the negative cases the subsequent biopsies revealed adenocarcinoma. Of the five cases reported on the original cytology as adenocarcinoma, two on review showed the features of florid gynaecomastia and this was confirmed on biopsy and three confirmed the initial diagnosis of adenocarcinoma. The cytological features of gynaecomastia which distinguish it from adenocarcinoma are discussed. PMID- 2102352 TI - Cervical cytology: terminology. PMID- 2102353 TI - Cytopathology of malignant mesothelioma. Reappraisal of the diagnostic value of collagen cores. AB - The identification of malignant mesothelial cells in cytological smears prepared from serous effusions is still hampered by the lack of features specific for mesothelial differentiation. We examined the diagnostic value of collagen cores within clusters of tumour cells in cytological smears prepared from effusions from 43 patients with malignant mesothelioma and of 62 cases of metastatic adenocarcinoma. In Giemsa-stained smears collagen cores were detected in 51% of the cases of malignant mesothelioma and in none of the smears with metastatic adenocarcinoma. Using the Azan stain, collagen cores were detected in 64% of the malignant mesotheliomas and 4% of the adenocarcinomas. Immunoelectron microscopy demonstrated that the collagen cores are largely composed of collagen type III fibrils and some elastin embedded in a homogenous extracellular matrix. It can be concluded that the presence of collagen cores within clusters of tumour cells is highly suggestive of mesothelial differentiation and a common finding in malignant mesothelioma. PMID- 2102354 TI - The number of nucleoli in benign and malignant thyroid lesions: a useful diagnostic sign in cytological preparations. AB - The slides of fine needle aspiration cytology specimens from 99 cases of cold thyroid nodules with known histology were reviewed and the number of nucleoli per nucleus counted and correlated with the different histopathological groups. Significant differences were observed between benign and malignant thyroid lesions in the number of nucleoli in the cytological material. Lower values were present in nodular goitres and follicular adenomas compared to carcinomas. In benign lesions the majority of nuclei contained one nucleolus and nuclei with two, three or more nucleoli were less frequent than in follicular, papillary, medullary and anaplastic carcinomas. Only one case of follicular adenoma had cells containing three or more nucleoli compared to more than half the cases of follicular carcinoma. PMID- 2102355 TI - Helminths and protozoa as an incidental finding in cytology specimens. AB - This is a description of some helminths and protozoa found incidentally in routine cytology specimens submitted to this laboratory. Eight different organisms are described together with the case history for each patient. All the specimens were stained with Papanicolaou technique. PMID- 2102356 TI - The Cervex: an ectocervical brush sampler. AB - The performance of a new ectocervical brush sampler--the Cervex--was compared with the Ayre spatula in 280 paired cervical smears. The Cervex smears were superior in quality of spread, transformation zone sampling in all degrees of cervical patency and in detection of histologically proven epithelial abnormalities, with a false negative rate of 10.9% compared with 20% for the Ayre. Improvement in predictive value was noted in atrophic samples, with increased cellularity and transformation zone representation. Difficulty has been encountered in obtaining adequate samples from the older woman and from those with iatrogenic scarring of the cervix. Although two-sampler techniques may be used, submission of high quality pan-cervical material from a single sampler onto one slide is economically and organizationally attractive. The Cervex seems capable of producing such samples and deserves further evaluation for routine screening. PMID- 2102357 TI - Fine needle aspiration cytology in a case of osteogenic sarcoma in Paget's disease. AB - A case of monostotic Paget's osteogenic sarcoma initially diagnosed by fine needle aspiration cytology is reported. The value of electron microscopy in this case is emphasized. PMID- 2102358 TI - Peripheral neuroectodermal tumour (neuroepithelioma) of the thoracopulmonary region: light and electron microscopic cytology. AB - We describe a case of peripheral neuroectodermal tumour of the thoracopulmonary region diagnosed by fine needle aspiration cytology. Light microscope examination revealed numerous small tumour cells arranged in large irregular aggregates occasionally delimiting empty vascular-type spaces or forming rosette-like structures. Cytologically the tumour cells showed a marked degree of nuclear anaplasia, scanty cytoplasm and long thin cytoplasmic processes. Electron microscopy revealed cells with characteristics of neuroectodermal differentiation. PMID- 2102359 TI - Defining the structural requirements of a biologically active domain of human IL 1 beta. AB - The immunostimulatory activity in vivo of the pleiotropic cytokine IL-1 beta can be retained by its nonapeptide VQGEESNDK, in position 163-171. A series of shorter and longer peptides around this position has been assayed for IL-1-like biological activity, in order to identify the structural requirements for full expression of adjuvant capacity. Elongated peptides, comprising the loop region 165-169 and up to six amino acids in the preceding beta strand or up to seven amino acids in the following beta strand, showed activity comparable or lower than that of the nonapeptide 163-171. This would indicate that the beta strand sequences are not required for optimizing the active conformation of the immunostimulatory IL-1 beta moiety. Accordingly, stabilization of the 163-171 peptide conformation by cyclization did not increase its biological activity. In contrast, the pentapeptide GEESN, corresponding the exposed loop 165-169 between two beta strands, had biological activity higher than that of the 163-171 nonapeptide and fully comparable to that of the entire IL-1 beta protein. Thus, the highly exposed fragment 165-169 within the IL-1 beta molecule may be the structure selectively responsible for the IL-1 beta immunostimulatory capacity in vivo. PMID- 2102360 TI - Inhibition of tumor necrosis factor-induced cell killing by tryptophan and indole. AB - Cells sensitive to the cytocidal effect of tumor necrosis factor (TNF) were protected against this effect when growth in the presence of elevated concentrations of tryptophan. Several other indole derivatives also provided protection against TNF cytotoxicity. Most effective were indole itself and its monomethyl derivatives, providing a degree of protection greatly exceeding that observed with tryptophan. Protection was also observed against the cytocidal effect of TNF applied in the presence of a protein synthesis inhibitor. The protective effect of tryptophan was largely dependent on preexposure of the cells, for several hours, to a high concentration of this amino acid. On the other hand, indole was protective also when applied to cells together with TNF, or even two hours after TNF application. The inhibition of the cytotoxicity of TNF by tryptophan and other indole derivatives may serve as a useful experimental tool in exploring the mechanisms and the physiological implications of TNF cytotoxicity. PMID- 2102361 TI - Autocrine growth factors secreted by the malignant human B-cell-line BJAB are distinct from other known cytokines. AB - BJAB, a EBV-negative Burkitt-like lymphoma, did not grow under suboptimal culture conditions in low concentrations of serum unless appropriate cytokines were added. A subclone of BJAB, Clone 13, however, could be kept in long-term culture under such conditions without added cytokines. This suggested that growth of BJAB Clone 13 was supported by autocrine growth factors (AGF). In fact, the supernatant of Clone 13 stimulated growth of the parental BJAB line and showed IL 1-like activity. Of several cytokines tested only AGF and IL-1 stimulated growth of BJAB. IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, GM-CSF, TNF-alpha, LT, IFN-gamma and TGF beta did not have this effect. The IL-1-like activity was completely neutralized by anti-IL-1 alpha antibodies. In contrast, AGF-activity was not affected by anti-IL-1 alpha. Rabbit antibodies produced against fractions enriched for AGF inhibited growth of BJAB. This inhibition was overcome by Clone 13-AGF, but not by IL-1 alpha. These data suggest that Clone 13-AGF is distinct from IL-1 alpha and might be a new cytokine. PMID- 2102363 TI - Cytokines in the nineties. PMID- 2102362 TI - Paraformaldehyde fixation of LPS-stimulated human monocytes: technical parameters permitting the study of membrane IL-1 activity. AB - The existence of IL-1 activity on the cell surface of stimulated mononuclear phagocytes is a matter of controversy. In particular, fixation of IL-1-expressing cells for 15 min in 1% paraformaldehyde (PFA) is commonly used to evidence such "membrane-associated" IL-1 activity but other authors have attributed this to passive leakage of IL-1 alpha from the cells and report no activity with longer fixation times. Using specific IL-1 alpha and IL-1 beta assays, we found that after the mild standard PFA fixation procedure, not only IL-1 alpha but also IL-1 beta were released into the supernatants for up to 96 h following fixation; membrane IL-1 activity cannot thus be measured in these conditions. However, using conditions in which neither immunoreactive IL-1 molecules nor IL-1 activity are found in the supernatants (i.e. assay at 144 h, increased fixation time), we were still able to detect IL-1 activity on LPS-stimulated, PFA-fixed monocytes. This activity was independent of the duration of PFA fixation and was inhibited by anti-IL-1 alpha but not anti-IL-1 beta antibodies. Our data thus underline the importance of technical conditions in the study of membrane-associated IL-1 activity. PMID- 2102364 TI - The treatment of mental disorders in hospitals. AB - This article examines mental disorders treated in Canadian general and psychiatric hospitals from 1971 to 1985-86. Significant changes occurred over the period of study. The analysis is based on hospital discharge data from eight provinces. For several decades, mental disorders have been among the leading causes of hospital use. In 1985-86, mental disorders accounted for about 10.8% of total days of care given in general hospitals. The total discharge rate for mental disorders treated in general and psychiatric hospitals declined moderately from 1971 to 1985-86. However the rate for functional psychoses has increased, while for other diagnoses the rates have decreased. The two diagnostic categories most often found in active treatment programs shifted position over the period. In 1971, the rate for general clinical disorders was almost twice that of functional psychoses; since 1981-82, the functional psychoses rate has exceeded the general clinical disorders rate. Discharge rates for functional psychosis for the elderly increased considerably, but remained stable in other age groups. This suggests that mental illness is being diagnosed more often in the elderly, and that treatment of their mental illnesses is more often undertaken. PMID- 2102365 TI - Divorces in Canada, 1988. AB - In 1988, a total of 79,872 divorces were granted in Canada. This was a 12.2% decrease from the 1987 total of 90,985, the highest ever in Canada. Divorce levels have been generally high in the late 1980s, but data for several more years are required before the impact of the 1985 Divorce Act can be accurately assessed. The 1988 divorce rate in Canada for married women aged 15 and over was 1,256 per 100,000. The highest rates occurred in Alberta (1,498) and British Columbia (1,407), and the lowest in Newfoundland (669) and Prince Edward Island (844). The average duration of marriages ending in divorce was 12.5 years. The largest number of divorces occurred after five years, followed by six and four years. Among divorces granted in 1988 under the 1985 divorce law, separation for not less than one year was cited as the grounds in almost nine out of ten cases. Of all children affected by custody orders for divorces granted under the 1985 law, 76% were awarded to the wife, 12% to the husband, 11% to joint custody, and fewer than 1% to a person other than the husband or wife. PMID- 2102366 TI - Lung cancer and smoking prevalence in Canada. AB - This article reviews lung cancer mortality and smoking prevalence in Canada. For men, age-adjusted lung cancer death rates are highest in Quebec and the Atlantic provinces, areas that had Canada's highest smoking prevalence twenty years ago. Rates are still rising in these provinces, though much less steeply than in the past. In Ontario and the Western provinces, lung cancer death rates for men have reached a plateau in recent years and rates in British Columbia even show signs of falling. Sizable declines in smoking rates among men have been reported in all provinces over the last twenty years, and lung cancer death rates for men can thus be expected to begin declining in this decade. For women, lung cancer death rates began to rise steeply in the 1960s, although remaining well below the rates for men. Rates for women nearly doubled in both the 1970s and 1980s. Smoking rates for women increased up to the early 1970s and declined only slightly since then. Lung cancer death rates for women can thus be expected to continue to rise until the end of the century. PMID- 2102367 TI - Births and birth rates, Canada, 1988. PMID- 2102368 TI - Marriages, Canada and the provinces, 1988. PMID- 2102369 TI - Coronary artery bypass surgery in Canada. AB - This report examines trends in the number and the rates of coronary artery bypass surgery (CABS) in Canada, performed over a six-year period from 1981-82 to 1986 87. The analysis includes comparisons of rates and events by sex, age and geographic location. In Canada 10,865 CABS were performed in 1986-87 representing a 39% increase over 1981-82. During the same period the rate of CABS rose to 43.2 per 100,000 population. In the twelve census metropolitan areas (CMAs) covered in this study, CABS increased 45.7% from 6,477 in 1981-82 to 9,439 in 1986-87, while hospital separations for Ischemic Heart Disease (IHD) increased by 22.6%. Regionally the coronary artery bypass surgery rate was lowest in Halifax at 62.4 per 100,000 population and highest in Ottawa-Hull at 131.8 per 100,000 population. The average annual proportion of CMAs ranged from 15.5% for residents in Halifax (84.5% for non-residents) to a high of 65.7% for residents in Montreal (34.3% for non-residents). Procedure rates increased consistently among the 65-74 and 75+ age groups, remained stable in the 55-64 age group, and decreased in the 35-54 age group. The variations among the CMAs may in part be due to the amount of resources available in each CMA, the demand for this type of service and perhaps to differing patterns of physician practice. PMID- 2102370 TI - Mental health statistics, 1985-86. PMID- 2102371 TI - 23rd annual meeting of the American Society of Nephrology (ASN). Washington, D.C., December 2-5, 1990. Program and abstracts. PMID- 2102372 TI - Histochemical analysis of CaMV 35S promoter-beta-glucuronidase gene expression in transgenic rice plants. AB - The cauliflower mosaic virus promoter is commonly used to drive transcription of chimeric genes in transgenic plants, including the cereals. To determine the tissue and cell types of cereal plants that the promoter functions in, transgenic rice plants containing a CaMV 35S promoter/GUS chimeric gene were analyzed for GUS activity. Insertion of a 35S/GUS chimeric gene at low copy number into chromosomal DNA of plants regenerated from electroporated protoplasts was confirmed by gel blot hybridization analysis of uncut and endonuclease-digested DNA. Quantitative measurement showed that GUS activity was some tenfold higher in rice leaves than in tobacco leaves whereas activities obtained for rice roots were similar to those reported for tobacco roots. Histochemical localization of GUS activity confirmed that the CaMV 35S promoter functions in cells of the leaf epidermis, mesophyll and vascular bundle. It is also active in the cortex and vascular cylinder of the root, but only marginally active in the root epidermis. The generally similar distribution and levels of GUS activity obtained in differentiated tissue of stably transformed rice plants indicates the value of the CaMV 35S promoter as a positive control for studies in gene activity in transgenic monocots and dicots. PMID- 2102373 TI - Developmental regulation of expression of the malate synthase gene in transgenic plants. AB - The cucumber malate synthase (MS) gene, including 1856 bp of 5' non-transcribed sequence, has been transferred into Petunia (Mitchell) and Nicotiana plumbaginifolia plants using an Agrobacterium binary vector. The transferred gene is found in variable copy number in different transformants, and is stably transmitted in each case as a single Mendelian character. Transgene mRNA accumulates in the seedling during the first three days of germination, then declines in amount as the cotyledons emerge from the seed. The decline is more pronounced in light-grown seedlings than in dark-grown seedlings. Expression of the MS transgene is also detected at a low level in petals of transformed Petunia plants. In these respects the pattern of MS gene expression is similar in cucumber and in transformed plants, showing that the transferred DNA fragment contains a functional MS gene. A 1076 bp fragment of 5' sequence was linked to the beta-glucuronidase reporter gene and transferred into Nicotiana, where it was shown to direct temporal and spatial patterns of expression similar to that of the complete MS gene. However, histochemical localisation of beta-glucuronidase activity demonstrated that the chimaeric gene is expressed not only in cotyledons of transgenic plants, but also in endosperm and some hypocotyl cells during early germination. The relevance of these findings to the control of malate synthase gene expression is discussed. PMID- 2102374 TI - In vitro processing of transcripts containing novel tRNA-like sequences ('t elements') encoded by wheat mitochondrial DNA. AB - We have recently described the properties of a wheat mitochondrial extract that is able to process, accurately and efficiently, artificial transcripts containing wheat mitochondrial tRNA sequences, with the production of mature tRNAs (P.J. Hanic-Joyce and M.W. Gray, J. Biol. Chem., in press). Such processing involves 5' endonucleolytic, 3'-endonucleolytic, and tRNA nucleotidyltransferase activities. Here we show that this system also acts on transcripts containing sequences corresponding to an unusual class of short repeats ('t-elements') in wheat mtDNA. These repeats are theoretically capable of assuming a tRNA-like secondary structure, although stable transcripts corresponding to them are not detectable in vivo. We find that t-element sequences are processed with the same specificity and with comparable efficiency as are authentic tRNA sequences. Because known t elements are located close to and in the same transcriptional orientation as active genes (18S-5S, 26S, tRNA(Pro)) in wheat mtDNA, our results raise the question of whether t-elements play a role in gene expression in wheat mitochondria. PMID- 2102375 TI - Rubisco genes indicate a close phylogenetic relation between the plastids of Chromophyta and Rhodophyta. AB - The genes for both subunits of Rubisco (rbcL, rbcS) are located on the plastome of the brown alga Ectocarpus siliculosus (Chromophyta, Phaeophyceae). The organization of these genes in the form of an operon was similar to that found in rhodoplasts, cyanobacteria and the plastids of Cryptomonas phi. Sequence analysis of the complete operon revealed a high degree of homology and great structural similarities to corresponding genes from two red algae. In contrast, sequence homology to Rubisco genes from chloroplasts and cyanobacteria was much lower. This clearly indicated a close phylogenetic relationship between the plastids of Rhodophyta and Chromophyta which seem to have evolved independently from the chloroplasts (polyphyletic origin). Our data suggest that the plastids of Chromophyta and Cryptophyta have originated from endosymbiotic unicellular red algae. Surprisingly, red and brown algal Rubiscos show a significantly higher degree of homology to that from a hydrogen bacterium than to those from cyanobacteria. PMID- 2102377 TI - Functional properties of the anaerobic responsive element of the maize Adh1 gene. AB - The functional properties of the anaerobic responsive element (ARE) of the maize Adh1 gene have been analysed using a transient expression assay in electroporated maize protoplasts. The ARE functions in both orientations although inversion of the ARE sequence relative to the TATA box element produces slightly weaker promoter activity under anaerobic conditions and elevated expression under aerobic conditions. Promoter activity under anaerobic conditions is proportional to the number of complete ARE sequences in the Adh1 promoter. The ARE contains two sub-regions and dimers of sub-region II are as efficient as the wild-type sequence in activating gene expression under anaerobic conditions. However, sub region I dimers do not appear capable of inducing gene expression in response to anaerobic stress. We conclude that sub-region II is essential for anaerobic induction of gene expression. Reporter gene expression remains constant when the spacing between sub-regions of the ARE is increased up to at least 64 bp, but increased spacing of 136 bp or greater abolishes expression in both aerobic and anaerobic conditions, indicating that a close association of the two sub-regions is required both for anaerobic responsiveness and for maximal levels of aerobic gene expression. When the ARE is placed upstream of position -90 of the CaMV 35S promoter, the ARE produces a high level of expression in both aerobic and anaerobic conditions. The general enhancement of gene expression driven by the hybrid ARE/35S promoter in aerobic conditions requires an intact sub-region II motif since mutation or deletion of sub-region II from the hybrid promoter reduces the level of expression to that observed for the truncated 35S promoter alone. In addition, mutation of the sub-region I sequences in the ARE/35S hybrid promoter does not significantly reduce expression in aerobic conditions, relative to pARE/delta 35S(-90), suggesting that sub-region I does not contribute to this general enhancer function. PMID- 2102376 TI - Localization of beta-phycoerythrin to the thylakoid lumen of Cryptomonas phi does not involve a signal peptide. AB - Recent investigations have shown that, in cryptomonads, the phycobiliproteins are located within the thylakoid lumen rather than on the stromal side of this membrane as found in cyanobacteria and red algae. To examine possible mechanisms involved in targeting this protein to the thylakoid lumen, the plastid-encoded cpeB gene from Cryptomonas phi was sequenced. This gene encodes an open reading frame of 177 amino acids that is highly similar to known beta-phycoerythrin proteins. cpeB is expressed as a monocistronic transcript of approximately 680 bases. The genes for the alpha subunits of phycoerythrin are not co-transcribed with cpeB nor located anywhere near it. No evidence of amino- or carboxy-terminal extensions or interior modifications involved in directing the Cryptomonas beta phycoerythrin into the lumen of the thylakoid could be detected. These data suggest that a novel mechanism may be involved in directing cryptomonad biliproteins to the thylakoid lumen. PMID- 2102378 TI - Characterization of a pollen-specific gene family from Brassica napus which is activated during early microspore development. AB - In this paper we describe the isolation and characterization of a genomic clone (Bp4) from Brassica napus which contains three members of a pollen-specific multigene family. This family is composed of 10 to 15 closely related genes which are expressed in early stages of microspore development. The complete nucleotide sequence of the clone Bp4 and of three homologous cDNA clones is reported. One of the genes (Bp4B) contained in the genomic clone is believed to be non-functional because of sequence rearrangements in its 5' region and intron splicing sites. The remaining genes (Bp4A and Bp4C), as well as the cDNA clones, appear to code for small proteins of unique structure. Three different types of proteins can be predicted as a result of the deletion of carboxy or amino terminal portions of a conserved core protein. These proteins all share a common alternation of hydrophobic and hydrophilic domains. A fragment of the genomic clone containing the gene Bp4A, as well as the non-functional gene Bp4B, was introduced into tobacco plants via Agrobacterium-mediated transformation. The functional gene Bp4A is expressed in transgenic tobacco plants and shows spatial and temporal regulation consistent with the expression patterns seen in Brassica napus. PMID- 2102380 TI - Nucleotide sequence of two anther-specific cDNAs from sunflower (Helianthus annuus L.). PMID- 2102379 TI - Structure and expression of two auxin-inducible genes from Arabidopsis. AB - Two genes from Arabidopsis thaliana related to the auxin-inducible Aux28 and Aux22 genes of soybean have been isolated. These genes belong to a small multi gene family and are similar to the soybean Aux gene family in the sequence of the predicted proteins, intron/exon locations, and auxin-enhanced expression of their transcripts. Application of auxin to 8-day old Arabidopsis plants, 4-day old etiolated seedlings, and suspension culture cells all resulted in enhanced Aux transcript levels. Comparison of the promoter sequences from the soybean and Arabidopsis genes yielded no significant sequence conservation; however, three regions of near sequence identity are present between the two Arabidopsis Aux genes. PMID- 2102381 TI - ORF209 of Dictyostelium discoideum mitochondrial DNA has a homologue in chloroplast DNA. PMID- 2102382 TI - The rDNA intergenic spacer region nucleotide sequence of Hordeum bulbosum L. PMID- 2102383 TI - Cloning and characterization of a cDNA for the cytosolic isozyme of plant pyruvate kinase: the relationship between the plant and non-plant enzyme. PMID- 2102384 TI - Characterization of cDNA clones for a virus-inducible, glycine-rich protein from petunia. PMID- 2102385 TI - Signal transduction for chemotaxis in Dictyostelium amoebae. AB - The signal for chemotaxis in D. discoideum is cyclic AMP. This molecule binds to cell surface receptors and triggers the production of inositol (1,4,5)trisphosphate which releases Ca2+ from non-mitochondrial stores. The subsequent chain of signal transduction events brings about the polymerization of cytoskeletal actin (associated with pseudopodium formation) within five seconds and the formation of a peak of cyclic GMP within 10 s. Evidence from streamer F mutants indicates that the cyclic GMP regulates the association of myosin with the cytoskeleton that occurs at 25-50 s and that this phenomenon is concerned with elongation of the amoebae during chemotactic movement. PMID- 2102386 TI - Chemoattractant stimulation of polymorphonuclear leucocyte locomotion. AB - Chemoattractants stimulate both cell locomotion and the orientation of this locomotion (chemotaxis) in polymorphonuclear leukocytes. Cell locomotion is a complex process which includes the coordinated protrusion of cell processes, formation of attachments to the substrate and contraction of the rear of the cell. To understand how chemoattractants regulate this process, it is helpful to dissect the process into components that can be examined separately. Comparison of these components in cells before and after stimulation with chemoattractant provides information about their regulation. In this review we focus on three components: how chemoattractants induce the development of cell polarity; how chemoattractants modulate cytoskeletal components (especially actin) to cause pseudopod protrusion; and how chemoattractant modulation of cell adhesions might contribute to cell locomotion. Spatial and temporal coordination of these and other components of locomotion result in efficient and directed cell movement. Our treatment of these questions is speculative and not comprehensive. We propose simple hypothetical models which can provide the reader with a conceptual framework that integrates the information available. PMID- 2102387 TI - The bacterial flagellar motor. AB - The bacterial flagellar motor is a remarkable molecular machine that converts chemical energy into work. Knowledge of the structure, genetics, and dynamics of the motor has expanded steadily. Recent progress is reviewed, with an emphasis on the dynamics of flagellar rotation. Previous results with tethered cells, which rotate slowly, are contrasted with recent work on swimming cells, whose motors turn very rapidly. Genetic evidence delineates a small set of proteins that are likely to participate directly in the process of torque generation. An explicit hypothesis for torque generation is described, in which roles are envisaged for each of these proteins. PMID- 2102388 TI - Pseudopodium activation and inhibition signals in chemotaxis by Dictyostelium discoideum amoebae. AB - The behaviour of Dictyostelium discoideum amoebae has been studied in natural cAMP waves and in controlled spatial and temporal gradients. Chemoattractant gradients induce responses which indicate that amoebae spatially compare concentration increases at different points on the cell surface. This allows them to respond to the relative spatial and temporal gradients in a manner that is little affected by the absolute attractant concentration over several orders of magnitude. The changes in turning behaviour, motility and morphology that are induced by attractant gradients are consistent with transduction of stimuli into two intracellular signals - one activating and the other inhibiting pseudopodium formation. The former measures the present attractant concentration at particular points on the cell surface - the local, current signal. The latter measures the average attractant concentration over the whole cell surface during the recent past - the global, past signal. Both signals may be part of a normal pseudopodium autoactivation and inhibition system responsible for amoeboid morphology and motility. Attractants could modulate this system to generate the complex behavioural responses observed. PMID- 2102389 TI - Membrane-cytoskeletal interactions in the early mouse embryo. AB - Differentiation in the early mouse embryo begins at the 8-cell stage when the blastomeres flatten against each other by active spreading movements and surface and cytoplasmic elements become concentrated in the apical (uncontacted) region of the cells. A ring of cortical myosin marks the demarcation between the contacted and the uncontacted cellular domains. The organization of the cortical contractile apparatus in the blastomeres bears a formal resemblance to that of other cells that are engaged in similar motile activities. It has been proposed that a flow of cortical filaments could provide the motor that powers these movements. The applicability of such a cortical flow model to the early embryo and the implications for cell flattening and cell polarization are discussed in this review. PMID- 2102390 TI - Cytoskeleton in Xenopus oocytes and eggs. AB - The Xenopus egg is a huge cell divided into compartments with distinct characteristics. The organization of the cytoskeleton reflects both the size of the egg and its regional differences. We review the information concerning the deployment and function of cytoskeletal elements during the changes in cellular organization accompanying oogenesis, oocyte maturation, and following fertilization. PMID- 2102392 TI - Synthesis, assembly and organization of the cytoskeleton during early amphibian development. AB - All eukaryotic cells undergo changes in three-dimensional organization which are controlled by the cytoskeleton. Early embryos execute cytoskeletal-mediated changes in a rapid and dramatic fashion and are therefore useful cytoskeletal model systems. This review highlights similarities and differences between somatic cell cytoskeletons and those of amphibian oocytes, eggs and zygotes. PMID- 2102391 TI - The myoplasm of ascidian eggs: a localized cytoskeletal domain with multiple roles in embryonic development. AB - The myoplasm of ascidian eggs is a localized cytoplasmic region containing a unique cytoskeletal domain. During ooplasmic segregation, the myoplasm moves first to the vegetal pole and then to the future posterior region of the fertilized egg, where it subsequently enters the muscle cell lineage during cleavage. In the vegetal pole region, the myoplasm defines a developmental center which later controls gastrulation and embryonic axis formation. In the posterior region, the myoplasm defines another developmental center, which specifies muscle cell development. Evidence is described suggesting that the integrity of the myoplasmic cytoskeletal domain is required for normal embryonic functions of the myoplasm. PMID- 2102393 TI - [An open letter: an old heart that beats in the future]. PMID- 2102394 TI - [The first permanent molars and palatal or mandibular variations]. AB - 101 children, each of them with two teleradiographies, were selected. The first X ray was taken at the time of the mixed dentition, the second one, when the permanent dentition was established. The purpose of the research is to show the oscillations of the palatine and mandibular planes, and their link to the movements of the first permanent molars. The palatine plane is found to swing between -7 degrees and +5 degrees with an average of -0.97 degree. The posterior part of that plane rocks downwards in 51% of the children. The limits are -7 degrees and -1 degree, with an average of -3.2 degrees. In 22%, the plane rocks upwards between +1 degree and +5 degrees with an average of +3.1 degrees. In 27% it moves parallel to itself. The posterior part of the mandibular plane varies between -6 degrees and +5 degrees, with an average of -1.1 degrees. It rocks downwards in 48% of the cases, between -6 degrees and -1 degree with an average of -3.9 degrees. In 22% of the children, this plane rocks upwards between +1 degree and +5 degrees with an average of +2.5 degrees. In 30%, it moves parallel to itself. The overall result is that the more the posterior part of the palate, or of the mandible moves downwards, the more the first permanent molars get straight or move forwards. PMID- 2102395 TI - [A comparative study of mandibular alveolar resorption following radiotherapy and/or chemotherapy in man]. AB - A prospective study of mandibular alveolar bone resorption has been achieved on 49 patients with upper aerodigestive tract tumor and treated by radiation therapy and/or a chemotherapy, on 30 patients who were not treated. All these patients were subjected to dental extractions followed by X rays in coronal and sagittal view, during at least one year, at the rate of one X ray every three months. The comparative study enabled to show a quite similar resorption for the two population, a slightly more important resorption on incisor and canine regions, and a stopping of the resorption about five months later according to dental extractions. Radiation therapy and chemotherapy (therapeutic doses) may not have significant influence on alveolar bone resorption after dental extractions. PMID- 2102396 TI - [The teratogenicity of 13-cis-retinoic acid on the mandibular-otic anlagen of the mouse embryo: a histological and histochemical approach]. AB - Oral administration of 400 mg/kg of 13-cis retinoic acid to 9 day pregnant mice gives rise to important maxillofacial malformations. The first manifestation of teratogenic effect is an increase of density of cell death arising in the dorsal part of the first two branchial arches at day 9.5. These two arches become hypoplastic at days 10 and 11, and the preskeletal anlagen appear too late in comparison to control embryos. Meckel's cartilage is too curvilinear and medially situated. Pre-ossicular and pre-mandibular blastemata develop with spatial distortions which are well analyzable at days 16 and 17. They give some arguments to discuss several features of normal early development of this area. PMID- 2102397 TI - Lymphatic vessels in inflamed human dental pulp. AB - Investigation has been performed on both the light and electron microscopic characteristics of the lymphatic vessels present in the dental pulp of human teeth which have been affected by serious carious lesions. These conditions provoke a severe inflammatory response resulting in structural and functional modifications of the tissue; increase of the tissue pressure is followed by the need for a more intensive lymphatic drainage. In the inflamed pulps, dilated lymphatic vessels with distended walls and "open junctions" between endothelial cells are detectable. On the other hand they lack certain endothelial structures which characterize the morphology of these vessels under normal conditions. In the pulpal regions affected by fibrotic proliferation shrunken vessels with irregular profiles are present. From these observations it is possible to obtain other information on the mechanisms regulating the lymphatic drainage in different structural and functional conditions of the interstitium. PMID- 2102398 TI - [A procedure for the 3-dimensional recording of human mandibular movements]. AB - A 3 dimensional process of recording the human mandible movements. Our system belongs to a general process made by the C.N.E.S. (Centre National d'Etudes Spatiales) in Toulouse; it records and measures the movements of body and limbs of spacemen. A test of this process is adapted for movements of mandible. The system uses a various instrumentation: two electronic cameras; infrared rays; reflectors; a multiplexor case; a magnetoscope; a dimultiplexor; a computer; two screens of control. Four reflectors are fixed on the face of subject; two others are fixed on a metallic system that is glued on the buccal face of inferior canines. These reflectors record the specific movements of mandible. Usual mastication and mastication on one side in turn are recorded in a young man with his natural teeth. Some graphs are showed for example. A data processing system measures the trajectory of mandible in the three dimensions of space, according to time and rapidity of movement. This video data processing seems to be a good method to analyze movements of mandible and mastication. PMID- 2102399 TI - [Conclusiveness of various diagnostic procedures for squamous cell carcinomas of the visceral cranium and the oral cavity as compared with histological evaluations]. AB - In 60 patients with primary squamous cell carcinomas of the oral cavity, clinical examination was complemented by 5 additional diagnostic procedures prior to surgery to assess tumor extension. Comparing these finding with the histological evaluation of the excised tissue demonstrated that, while the TNM classification remains the foundation of all tumor diagnostic procedures, the use of radiography, bone scintigraphy and CT is indispensable to ascertain the amount of tissue to be excised. CT competes with B-scan sonography in cervical lymph node diagnostics. Tumor scintigraphy has been found to be an unreliable method. PMID- 2102400 TI - [Use of low-molecular fluorescent dyes for localizing tumor cells]. AB - A novel fluorescence microscopic technique, based on the application of low molecular fluorescent dyes, was used to study the expression of the enzyme guanidinobenzoatase in malignant tumors of the head and neck area. Frozen sections have shown that moderately and highly differentiated squamous cell carcinomas express this enzyme, particularly in the area of tumor invasion. The protease is capable of breaking down fibronectin, an important component of the extracellular matrix. In less differentiated squamous cell carcinomas as well as malignant melanomas almost all tumor cells exhibited guanidinobenzoatase activity. The fluorescence microscopic technique presented here provides a fast and easy method for the localization of tumor cells. At the same time it provides a better understanding of the biological control of a tumor-associated protease, thus furnishing important new information on the invasion behavior of malignant tumors. PMID- 2102401 TI - [Abscess of the cervical soft tissues and the mediastinum resulting from an infected jaw cyst]. AB - A woman is described in whom an infected radicular cyst of the mandible resulted in a cervical phlegmon with abscess formation and spreading into the superior mediastinum. PMID- 2102402 TI - [Deep freeze bank bone material for maxillofacial reconstructions]. AB - The use of deep freeze bank bone grafts in maxillofacial surgery is described. The prerequisites for establishing a bone bank and the selection of bone graft material and donors are discussed. The use of deep freeze graft material is possible in virtually any area of maxillofacial surgery. Thus, patients with minor defects can be spared the stress of autogenous bone removal. The potential risk of disease transmission is emphasized. PMID- 2102403 TI - [Results after treatment of facial fractures with the Wurzburg titanium miniplate system]. AB - The basic principles of anatomy and materials science, forming the foundation for the application of the Wurzburg titanium miniplate system, are described in detail. Based on 252 midfacial fractures and 315 mandibular fractures treated with this Miniplate system between 1984 and 1987, the clinical results of using this system in traumatology are discussed. PMID- 2102404 TI - [Distant metastases and second carcinomas in patients with malignancies of the oral cavity]. AB - Between July 1st, 1984, and December 12th, 1988, a total of 135 patients underwent surgery for carcinomas of the oral cavity at the Maxillofacial Surgery Department and the Institute for Pathology of the University Hospital of Zurich. In 121 cases the malignancies involved the mandibular area including the floor of the mouth and the tongue, in 14 cases the maxillary area without the sinuses. 18 patients (13.3) had distant metastases and 8 patients (5.9%) had second carcinomas; 2 patients had both second carcinomas and metastases of their oral cavity carcinomas. The average age of the patients with distant metastases was 57.8 years, that of patients with second carcinomas 52.2 years. Diagnosis, treatment and the course of the disease are discussed. PMID- 2102405 TI - [Biomechanic and histomorphometric studies of HIP titanium glass ceramic, a new implant material, compared with glass ceramics, titanium and titanium alloy]. AB - Interfacial tensile strength and quantitative histomorphological properties of alloplastic implant materials for hard tissue application were studied in animal models. Physico-chemical bonding in the order of 1 N/mm2 of bone to glass-ceramic (Ceravital) was demonstrated independent of magnitude of surface roughness with mineralized bone in excess of 80% at the implant interface. No bone-bonding, but contact of mineralized bone at the metal surface was observed in pure titanium and titanium alloys (Ti6Al4V, Ti5Al2, 5Fe) with smooth surfaces. Rough or porous surfaced specimens, however, exhibited mechanical interlocking and interdigitation, thus yielding interfacial tensile strength of up to 4 N/mm2 in geometrically porous or madreporic surfaces. The new composite material HIP Titanium-glass-ceramic (Ceravital) displayed physico-chemical bonding to bone as well as mechanical interdigitation within the secondary porous structure, thus giving support to expectations that HIP-Titanium-glass-ceramic coated implants should perform superior than bulk materials. PMID- 2102406 TI - [Results of arthroscopic surgery of the TMJ]. AB - The article describes results of arthroscopic TMJ surgery in patients with limited jaw opening. In 21 patients, 16 women and 5 men, one or both joints were diagnosed arthroscopically and surgery was performed during the same session using special microsurgical instruments. The most important part of the procedure was loosening adherences under endoscopic view. Jaw opening increased by up to 20 mm in 19 out of the total of 21 patients. Complications such as are reported in the literature were not observed in any of our patients. Jaw opening decreased only in 2 patients due to lack of cooperation. PMID- 2102407 TI - [Selection of the approach to the TMJ under esthetic aspects]. AB - The esthetic results of 128 TMJ surgeries are reported. 81 TMJs were treated via the preauricular, 47 via the retroauricular approach. The preauricular approach with a curved or modified line of incision is characterized by an almost unnoticeable scar, particularly if the incision is placed into a preauricular crease or pit. Leaving the scar in an invisible area, the retroauricular approach is esthetically superior to all other procedures. Both approaches involve a minimum risk for complications, if the correct technique avoiding traumatization of the marginal branch of the facial nerve is used. Considerations related to the choice of the different approaches are discussed with respect to their characteristic features. PMID- 2102408 TI - [Language acquisition in cleft lip-palate (CLP) children. 2. Linguistic diagnosis and therapeutic approaches]. AB - The major tests and methods used in language acquisition diagnosis in CLP children of 3 months to 6 years of age are described. Apart from methods for phonetic analysis, such as spectrography, emphasis is being placed on the assessment of listening by hearing and of semantic and meta-linguistic acquisition. Additional information is obtained on the motoric, cognitive and social development (for detecting any possible multiple handicaps in these areas). In this context the major problems covered in cleft palate parent groups are also pointed out. Finally, the speech therapy provided for preschool children with severe speech problems (as compared with the control group) is outlined. PMID- 2102409 TI - [Chloroquine-induced isolated palatal hyperpigmentation]. AB - We report about an isolated slate-greyish discoloration of the palatinum during chloroquine therapy of cutaneous lupus erythematosus of a 28-year-old woman. The hyperpigmentation is harmless. It is due to increased melanin synthesis and not due to deposition of the drug or its metabolites. The oculist should be consulted however, to exclude possible retinopathia. PMID- 2102410 TI - [Gardner's syndrome]. AB - Gardner's syndrome is a dominant, familial cancer syndrome. It is characterized by intestinal polyposis, multiple osteomas, especially of the skull, and various soft tissue tumors (such as epidermal cysts or desmoid tumors). Late age of onset is the main feature distinguishing it from other polyposis syndromes. The risk of malignancies developing during adult life is virtually 100%, and colectomy is mandatory. Since extracolonic manifestations are very often the first symptoms seen by the physician, it is very important to know that they are indicative of Gardner's syndrome and associated with intestinal polyposis. PMID- 2102411 TI - [Lymphomas with oromaxillofacial manifestations]. AB - Out of a total of 48 patients with malignant lymphomas of the maxillofacial area, only 2 patients had been referred with a correct tentative diagnosis within a period of 11 years. In 83% the main symptom was painless swelling of the affected structures. Almost 50% of the extranodal manifestations were found in the mouth. PMID- 2102412 TI - [Immunohistochemical results obtained with bromodeoxy uridine (BUdR) labelled tumors of the head and neck]. AB - In a prospective study 17 patients with oral PE carcinoma were given bolus injections of a non-toxic dose of BUdR, 4 hours prior to tumor surgery. BUdR replaces thymidine in the DNA of those cells which are in the S phase at the time of application. The resected tumor material was fixed in formalin and embedded in paraffin for immunohistochemical analysis using a monoclonal antibody against BUdR incorporated in DNA. The BUdR-storing cells were evaluated in 4 histologically different tumor areas. A total of 1600 cells was evaluated in each primary tumor or, in given cases, each lymph node metastasis or recurrence. In contrast to flow cytometry, this morphological method proved useful not only in comparing the number of BUdR-labelled cells with the total tumor cell population in different carcinoma segments, but also in correlating the focal proliferation tendency with the regional degree of differentiation and the number of mitotic cells even in morphologically different tissue segments. More often than not these results showed an increase in the average BUdR storage rate with increasing dedifferentiation and increasing rate of mitosis. Nevertheless, this is not the rule for each individual case. Some tumors displayed a relatively high proliferation tendency and BUdR storage rate in more highly differentiated areas (marked keratinization). Some poorly differentiated tumors or tumor areas, on the other hand, exhibited relatively low storage rates. Possibly, immunohistochemical analysis of a biopsy specimen after preoperative BUdR application may provide information on the radiosensitivity of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102414 TI - [Surgical treatment of fronto-maxillary tumors]. AB - Surgical treatment of fronto-maxillary tumors requires interdisciplinary cooperation of maxillofacial surgeons and neurosurgeons. Depending on the site and extension of the tumor, it may be necessary to resort to generous excision of the frontal, temporal, sphenoid, zygomatic bones, orbita and nasal bone, including their soft-tissue covers; possibly even exenteration of the orbita and excision of dura are required. Closure of open subarachnoid space is mandatory. Dural defects are supplied with periosteum or free fascial grafts. Calvarial defect are usually repaired with large rotation flaps of the scalp. In exceptional cases pedicled flaps from more remote areas or microsurgically vascularized grafts are used. The facial area is supplied either with flaps or split skin grafts, depending on the situation. Open paranasal sinuses must be drained via the nasal sinus. Remaining facial defects are treated prosthetically. PMID- 2102413 TI - [Osseous metastases in upper and lower jaws]. AB - 18 cases of metastases to the jaws in the last 10 years obtained from the Clinic of Maxillofacial Surgery and the Department of Pathology, University Hospital Zurich, are described. They were seen in patients with carcinoma of the breast, lung, prostate gland, uterus and seminoma of the testis. In 16 cases the metastases were situated in the mandible, in 2 cases in the maxilla. The average age of these patients was 61.6 years with no sex predilection. The initial symptoms were pain swelling. In 4 cases a pathologic fracture was diagnosed. The majority of the metastatic lesions are osteolytic in nature. The metastases were diagnosed, in average 3.3 years after diagnoses of the preliminary tumor. In 2 cases the metastases were diagnosed before the occult primary tumor. Death usually ensues 1 year after diagnoses. PMID- 2102415 TI - [Oral and maxillofacial tumors and alcoholism]. AB - The importance of a holistic treatment approach in patients with oral and maxillofacial tumors is emphasized both under psychological and medical aspects. The objectives of psychological care, which has been integrated into the treatment concept of the University Hospital of Munster since the beginning of 1988, are particularly related to dealing with and mastering of the disease and the treatment of alcoholism, a frequently observed problem. This concept is described in detail by Kolbe and Hemprich (1989). The article covers the experience gained in the first year since psychological care has been integrated. PMID- 2102416 TI - [Psychological effect of corrective surgery in female patients with structural and functional abnormalities of the jaws]. AB - 20 young women (16 to 31 years of age) who underwent orthognatic surgery between 1979 and 1984 were subjected to an evaluation of their dental, orthognatic and psychological catamneses. The psychological results concerning operation motivation, preoperative stress and information, early postoperative condition and subjective assessment of the operative result are reported and discussed. Proposals are made to improve pre- and postoperative treatment of these patients. PMID- 2102417 TI - [NMR imaging in the diagnosis of orbital fractures with loss of function]. AB - According to the results of this study NMR imaging seems to be the method of choice in radiodiagnosis of orbital wall fractures for demonstrating impactions or prolapses of orbital contents. It is superior to classic radiography or computerized tomography. PMID- 2102418 TI - [Posterior dislocation of the articular disc--a rare case?]. AB - The aim of this paper is to describe a very seldomly observed case of a unilateral dorsal luxation of the disc of the temporomandibular joint. The luxation happened during intense laughing in a movie-theater and was first noticed two days later. The diagnosis of this unilaterally shifted and fixed mandible was clearly seen on the double-contrast arthrogram. The therapy of repositioning the joint was done under short-duration general anaesthesia followed by a 2 weeks immobilisation of the jaws. PMID- 2102419 TI - [End-to-end anastomosis of the lacerated parotid duct]. AB - The case of a patient with an extensive vertical laceration of the right cheek involving Stensen's duct is reported. Treatment of parotid duct injuries varies with location and type of the injury. Immediate repair of the duct can prevent troublesome and lengthy treatment at a later date, whereas ineffective primary management may lead to complications and render treatment much more difficult. PMID- 2102420 TI - Silicone cap osteoarthroplasty for temporomandibular joint ankylosis, with a kinesiologic study. AB - In spite of the small experiences, silicone capping with gap osteoarthroplasty in high level is thought to be one of the valuable procedures for TMJ ankylosis. In the view of kinesiology, a normal joint cannot be reconstructed, because the mandibular movement in ankylosis is far from the normals. PMID- 2102421 TI - [Results of perioperative antibiotic prophylaxis in orthognathic surgery]. AB - Intraoral approaches are commonly used for the surgical correction of dysgnathia. Because of the massive contamination of these wounds, antibiotic therapy is considered necessary. In a study on an unselected patient population the benefit of perioperative short-term prophylaxis is compared with that of postoperative long-term treatment. The results have shown perioperative short-term prophylaxis with penicillin to be extra-ordinarily effective vis a vis long-term treatment with oxytetracycline. Inflammatory complications did not occur, whereas in a control group they were observed in almost one fifth of the patients. In addition, this form of short-term prophylaxis is far more economical. The differences are statistically significant. PMID- 2102422 TI - [Long-term alternations in the hypopharyngeal respiratory tract after mandibular setback]. AB - 10 patients were evaluated retrospectively for their long-term changes in hypopharyngeal airway space after surgical correction of mandibular prognathism. All patients had undergone mandibular setbacks by way of bilateral sagittal split osteotomies with rigid fixation. The cephalometric evaluation of the hypopharyngeal airway space was based on stable craniofacial landmarks. The results of this study indicate that mandibular setbacks procedures create relative narrowing of the hypopharyngeal airway space, which in isolated cases might contribute to the development of an obstructive sleep apnea syndrome. The clinical implications of these findings are discussed. PMID- 2102423 TI - [Inverted papilloma: implications for the oral and maxillofacial surgeon]. AB - 7 patients with inverted papillomas of the maxillofacial area were subjected to a post-treatment evaluation. Inverted papillomas were found in maxillary and frontal sinuses, ethmoid cells, nasal septa and as isolated lesions in the mucosa of the mandibular alveolar process. Apart from an inverted papilloma, one patient also had a mucoepidermoid carcinoma. The tendency to recur correlated well with the surgical approach. Radical removal of the mucosa must be called for as primary therapy in the paranasal sinus area. In order to safely exclude a concurrent carcinoma, the entire resected material must be examined histologically. PMID- 2102424 TI - [PVP granuloma--a complication in the treatment of facial neuralgia]. AB - A 61-year-old female patient suffering from neuralgiform facial pain developed a PVP granuloma, after she had received peripheral conduction anesthesia treatment with a local anesthetic containing polyvinylpyrrolidone over many years. The clinical symptoms and treatment of this pseudotumor as well as the features distinguishing it from real tumors, particularly chordomas, are indicated. PMID- 2102425 TI - [Hereditary intraoral fibromas and exostoses]. AB - The formation of exostoses of the upper and lower jaw is a frequent finding and should be treated for esthetic and functional reasons. An unusual case of severe palatal fibromas and concomitant vestibular exostosis in a 36-year-old woman is presented. Identical symptoms are found in the patient's father and her 8-year old daughter. PMID- 2102426 TI - [Clinical features and treatment of cutaneous carcinoid]. AB - An exemplary case of a 67-year-old patient with multiple cutaneous metastases of a pulmonary carcinoid primary tumor is presented. The cardinal symptom was severe painfulness of the skin tumors. With chemotherapy the tumor disease advanced. In presenting this case and providing a review of the literature, the primary importance of surgery even in the case of a metastasizing carcinoid is emphasized. PMID- 2102427 TI - [Clinical features and treatment of osteogenic sarcoma of the jaws]. AB - 24 patients with osteogenic sarcomas of the jaws were entered in a retrospective study. 79.2% of the cases had local relapses or distant metastases, usually within the first 2 years following surgery. With primary surgical treatment the 5 year disease free survival rates in cases with maxillary manifestations ranged at 22.1% and with mandibular sarcomas at 18.2%. Thus, prognosis for osteogenic sarcomas of the jaws is to be assessed as being no more favorable than for sarcomas of the extremities. A review of the literature shows that aggressive pro and postoperative chemotherapy must be postulated apart from radical tumor resection to improve the survival rates. PMID- 2102428 TI - [Taurodontism in patients with sex chromosome anomalies]. AB - Out of a population of 61 patients with sex chromosome aberrations we could examine 25 patients with Klinefelter's syndrome and one female patient with triple X syndrome for taurodontism. Taurodontic molars were found in 6 out of 25 patients with Klinefelter's syndrome and in the patient with triple X syndrome. PMID- 2102429 TI - [Primary and secondary reconstruction of the frontal sinus using the titanium screen system]. AB - The objective of surgically maintaining shape and lumen after frontal sinus injuries can be achieved by using various types of osteosynthesis and reconstructive materials. In cases with extensive fracture defects we recommend alloplastic anterior wall reconstruction using titanium screens as an alternative to conventional procedures. PMID- 2102430 TI - [Joint-sparing mobilization of TMJ ankylosis]. AB - The causes leading to ankylosis are reviewed and operative approaches to avoid "block-resection" are briefly outlined. 2 patients with fibrous ankylosis are presented, with the affected area visualized through computer-tomograms. Each patient underwent only resection of the lateral exostosis causing restricted movement. Follow-up tomograms of the 2 patients are offered. PMID- 2102431 TI - [Clinical, radiographic and endoscopic evaluation of the maxillary sinus after maxillary osteotomy]. AB - 36 osteotomies performed between 1982 and 1988 involved opening the maxilla. Postoperative clinical, radiographic and endoscopic follow-up revealed that the majority of the patients had no or only minor pathological alterations of the maxillary sinuses. Sinuscopy showed only 2 maxillary sinuses to have more extensive mucosal alterations. Remarkably, it was particularly the osteosynthesis material protruding into the maxillary sinus that was surrounded by or overgrown with non-irritated mucosa. PMID- 2102432 TI - [Ibuprofen for pain treatment following dental surgery. A comparative prospective randomized study]. AB - The efficacy of postoperative pain treatment after dental surgery procedures depends not only on the type of substance used but also on the time it is taken and the dose administered. Direct postoperative administration of 400 mg Ibuprofen (2nd administration after 6 hours) resulted in considerably greater pain relief, without increasing the risk for the patient, than when the drug was taken as required. PMID- 2102433 TI - [Optimized analgesic sedation. Improved possibilities in high-risk patients through the use of pulse oximetry]. AB - The pulse oximeter allows quick assessment of a patient's respiratory function and the early detection of imminent hypoxia (Singer and Thomas, 1988). It is a useful means in non-continuous circulatory monitoring and is not stressful to the patient. In analgosedation it enables the operator to monitor the respiratory effect of the drugs used with almost no delay, to take the counter-measures required and to adapt the dosage to the individual requirements of each patient. PMID- 2102434 TI - [Animal models for investigating the possibility of cleft lip surgery in utero]. AB - The continuous refinement and further development of prenatal diagnostics and of anesthesiologic as well as operative techniques have rendered fetal surgery a point of major clinical interest. In view of the present clinical results of prenatal surgery in the human fetus, the question arises, if it is wise to include the correction of craniofacial malformations in the indications for intrauterine surgery and thus to allow the qualitative advantages of fetal wound healing patterns to be utilized. In the present experimental study an animal model using rabbits is presented, which allows successful intrauterine surgery of the craniofacial area. PMID- 2102435 TI - [Extracorporeal shock wave lithotripsy of sialoliths as a new noninvasive outpatient treatment concept]. AB - The rapid progression of Extracorporeal Shock Wave Lithotripsy (ESWL) opens new possibilities in painless non-invasive treatment of salivary gland stones under local therapy. Procedure and first very promising success in the clinical appliance to sialolithiasis is shown as follows. PMID- 2102436 TI - [Nd-YAG laser probe in maxillofacial surgery]. AB - The characteristic feature of Nd-YAG lasers is their great depth of tissue penetration. Surface irradiation using a handpiece has a penetration depth of 8 10 mm. To reach deeper structures the area may be irradiated using a mini catheter with a flexible Nd-YAG probe. The specific procedures involved and the range of clinical applications are described in detail. PMID- 2102437 TI - [Bone regeneration following the implantation of osteoblasts from cell cultures]. AB - An animal model utilizing 26 inbred rats was aimed at the question if the regeneration of bone tissue is enhanced by implantation of osteoblasts previously cultured in vitro. Bone tissue was harvested from inbred rats (Lewis) and a cell line of rat osteoblasts was established. The osteoblasts were cultured in vitro and multiplied in three passages. Characterization of the cells was by various methods. Monocortical defects were created in the distal portion of the rat femurs by drilling; and the cells, embedded in 25% bone gelatine, were reimplanted into these defects. After observation periods of varying lengths, the femurs were examined radiographically and bone growth in the defect area was evaluated histologically. The results of this study indicated that there was an initial effect of the reimplanted cultured osteoblasts on the bone growth pattern. At a later point in time this effect could no longer be demonstrated in the young, healthy rats. PMID- 2102438 TI - [Comparison of the mechanical properties of resorbable bone substitutes]. AB - The mechanical properties of blood clots stabilized with collagen, gelatine and alginate sponges were compared with the oid of thrombelastography and volumetric tests. The collagen sponges were distinctly inferior to gelatine and alginate in stabilizing the clot against retraction. There was no evidence of any interaction between collagen and blood clot. PMID- 2102439 TI - [Lyophilized cartilage--an antibiotic carrier]. AB - Human lyophilized bruised costal cartilage was tested in vitro for its ability to act as a carrier medium for antibiotics. A remarkable capacity of accumulating streptomycin, gentamicin, tobramycin, vancomycin and ciprofloxacin was observed; whereas beta-lactum antibiotics and fosfomycin were released at a high rate. This release pattern was not influenced by the sterilization procedure, but rather by the size of the cartilage granula. Lyophilized cartilage--rehydrated in antibiotic-solutions--be helpful adjunct in the surgical management of osseous infections. PMID- 2102441 TI - Definition of bound residues. PMID- 2102440 TI - Characterization of a second highly conserved B-type lamin present in cells previously thought to contain only a single B-type lamin. PMID- 2102442 TI - Overview on bound residue issue--regulatory aspects. PMID- 2102443 TI - Risk assessment and animal drug residues. PMID- 2102444 TI - Overview of bound residue chemistry. PMID- 2102445 TI - Is the toxicity of cysteine conjugates formed during mercapturic acid biosynthesis relevant to the toxicity of covalently bound drug residues? AB - In this brief review, we have focused on the relevance of the data on cysteine conjugate toxicity to the potential hazard of bound drug residues. A resonable scenario, based on assumptions as well as literature data, has been presented for the release of cysteine conjugates of drug residues from protein. Furthermore, we have presented evidence that should this occur, the conjugate would be bioavailable. Finally, the mechanisms which could lead to cysteine conjugate induced toxicity have been discussed. The question which must be answered is, how realistic is the treat of toxicity to the consumer from cysteine-bound drug residues in food products? Based on the data presented here, the danger is minimal, though it cannot be excluded. This is particularly true of the potential for renal complications. However, an important caveat which must not be overlooked is the marked species differences in cysteine conjugate toxicity. Though S-(1,2LD50-dichlorovinyl)-L-cysteine (DCVC) is a renal toxin in rodent models (LD50 = 66-83 mg/kg) [88], a single dose of 4-5 mg/kg causes fatal aplastic anemia in calves [44,59]. Though such a response has never been reported for any other cysteine conjugate, these data must be reckoned with if attempts are made to place acceptable limits on the amount of residues allowable in food products. PMID- 2102446 TI - Biochemical and physiological dispositions of glutathione conjugates. PMID- 2102447 TI - Formation and biological evaluation of ronidazole bound residues. PMID- 2102448 TI - In vivo and in vitro metabolic studies of furazolidone: a risk evaluation. PMID- 2102449 TI - Summary of bound residue chemistry session. PMID- 2102450 TI - Rationale for biological approaches to evaluate a bound residue. PMID- 2102451 TI - Relay toxicity. PMID- 2102452 TI - EEC perspectives on relay toxicity and bioavailability studies. PMID- 2102453 TI - The rat as a drug residue bioavailability model. PMID- 2102454 TI - Potential use of isolated organ or tissue preparations in the assessment of biological activities of bound residues. PMID- 2102455 TI - Strategies for the use of genetic toxicity tests. PMID- 2102456 TI - Validity of in vitro testing. AB - In summary, the extent of toxicity studies which can be carried out with bound residues of nitroimidazole drugs will be dictated by the availability and the amount of residues that can be produced. For evaluating their toxicity the use of the Salmonella assay, which has been proven to be sensitive for the parent drugs, is proposed. Furthermore, it is suggested that the toxicity of bound residues for in vivo effects should be investigated in cells of target tissues, such as the epithelial cells of the gastrointestinal tract. Nuclear aberration and sister chromatid exchange assays in this tissue would be good candidates for evaluation. It should be pointed out also that an examination of the literature for genotoxic effects of nitroimidazole drugs reveals an apparent contradiction, especially in the context of genotoxicity testing strategy discussed above. It appears first that these drugs are potent mutagens in vitro in microbial systems (Salmonella and yeast). However, they are not active in mammalian cells in vitro, in both mutation and chromosomal aberration assays, as well as in vivo, in assays such as the dominant lethal test and the micronucleus assay. Thus, it may be of interest to speculate that, although these drugs are in vitro mutagens, they may not be in vivo mutagens in mammals. Their tumorigenic effects, which have been detected at high doses in rodents, may, therefore, be due to other than genotoxic activity. To resolve this conflict, reassessment of genotoxicity of these drugs in vivo would be a worthwhile pursuit. In addition, such seeming discrepancies would also argue strongly for toxicity screening to be conducted in a battery of complementary short-term in vitro and in vivo tests. This would help insure the likelihood of detection of at least some meaningful biological activity, which would serve to flag chemicals warranting further testing. PMID- 2102457 TI - Correlation of multiple biological techniques. PMID- 2102458 TI - Biological models for assessing bound residues--comments. PMID- 2102459 TI - Application of the pharmacological screening process. PMID- 2102460 TI - Application of the basic toxicological screening process to problems in bound residue toxicity. PMID- 2102461 TI - The integration of pharmacological and toxicological testing of tissue residues in the evaluation of their human food safety. PMID- 2102462 TI - Nitroimidazoles: proposed studies on the toxicity of bound residues. PMID- 2102463 TI - Proposed plan for a unified approach for evaluating nitrofuran residues. PMID- 2102464 TI - Biological evaluation of aflatoxins and metabolites in animal tissues. PMID- 2102465 TI - Development of a unified approach to evaluate the toxicological potential of bound residues. PMID- 2102466 TI - Prolactin inhibition of pregnant mare's serum stimulated follicle development in the rat ovary. AB - Prolactin (PRL) effects on the female reproductive system have been presumed to occur primarily at the hypothalamic-pituitary level. The following studies were designed to evaluate whether PRL can directly alter gonadotropin actions at the ovarian level. In the first experiment, 10 groups of 7 cycling adult female rats were given a daily dose of pregnant mare's serum (PMS: 25 IU) and either saline (SAL) or PRL (0.25, 0.8, 2.5, 8, or 25 micrograms) twice daily for 4 days. In the second experiment, PMS (6 doses: 0-75 IU/d; 16 animals/dose) was administered to all animals while half the animals at each PMS dose received PRL (25 micrograms twice daily) and half received an equal volume of diluent. Finally, hypophysectomized (hypox) adult rats (n = 5-6/group) received 25 IU PMS/d and PRL (0-75 micrograms) twice daily. An additional group received 0 PRL and 0 PMS. Ovarian weight and histology were evaluated at the completion of each study. In the first experiment, PRL inhibited PMS-stimulated ovarian weight gain in a dose dependent manner (p less than 0.01). Numbers of preantral (p less than 0.005) and antral (p less than 0.05) follicles were decreased in animals receiving an inhibitory dose of PRL (25 micrograms BID) compared to controls. In the second experiment PRL (25 micrograms BID) again inhibited PMS-stimulated ovarian weight (p less than 0.01) at all doses of PMS. Finally, in hypox animals, PRL inhibited PMS-stimulated ovarian weight gain (25 and 75 micrograms PRL: p = 0.001), and mean number (p less than 0.001) and diameter (p less than 0.001) of antral ovarian follicles (8-75 micrograms PRL) compared to controls. In summary, administration of PRL inhibited PMS-stimulated ovarian weight gain, and antral follicle diameter (in hypox animals only) and number in adult female rats suggesting that in states of hyperprolactinemia, PRL alters gonadotropin-mediated activities (i.e., folliculogenesis) directly at the ovarian level in addition to its hypothalamic and pituitary actions. PMID- 2102468 TI - Condoms--now more than ever. PMID- 2102467 TI - Cross-reaction of albumin with polyclonal LH antibody on western blots. AB - When pituitary tissue was subjected to Western blot analysis utilizing polyclonal antibody NIDDK-rLH-S-10, bands at 17 and 19 Kd representing LH subunits were identified. In addition, a high molecular weight 66 Kd band was seen. Surprisingly this high molecular weight band was also seen in rat cerebral cortex, brain stem, hypothalamus, spinal cord, lung, liver, pancreas, spleen, kidney, testis, and serum. Antibody preabsorbed with iodination grade rat LH antigen no longer recognized the 17 and 19 Kd bands in pituitary, but recognized the 66 Kd bands in pituitary and the other tissues examined. Since 66 Kd is the molecular weight of albumin, we found that antisera to rat albumin recognized this same high molecular weight band in the tissues examined. Preabsorption of LH antibody with albumin reduced the ability of that antibody to recognize this 66 Kd. A monoclonal antibody to bovine LH beta-subunit recognized only the LH protein in anterior pituitary, but no high molecular weight band in either pituitary or the other tissues studied. Finally, 10, 100, and 1000 micrograms of rat albumin caused no substantial interference under conditions of RIA. We conclude that the polyclonal antibody, provided by the NIH, is excellent for conditions of RIA, but caution must be exercised when it is used for Western analysis where some lots of this antibody may recognize other unrelated proteins. PMID- 2102469 TI - Standardized photodocumentation in facial plastic surgery. PMID- 2102470 TI - The skyline view: a new perspective for rhinoplasty surgery. PMID- 2102471 TI - Five-year facial plastic experience with computer imaging. PMID- 2102472 TI - Computer imaging: the manufacturer's perspective. PMID- 2102473 TI - Lighting considerations in computer imaging. PMID- 2102474 TI - Quantitative facial aesthetic evaluation with computer imaging. PMID- 2102475 TI - Image thyself. PMID- 2102476 TI - Marketability of computer imaging. PMID- 2102477 TI - Potentiation of inner ear damage following electron beam irradiation with CDDP administration. AB - This study was designed to examine the combined ototoxic effects of cisplatin, an antitumor platinum compound, administration and electron beam irradiation on the inner ear of guinea pigs, histopathologically. One group received saline solution 4 ml/kg/day and the other group received cisplatin of 2 mg/4 ml/kg/day for five consecutive days. The right temporal bones of all animals of both groups were exposed to the electron beam of 14 Gy/day 3 hours after the daily injection of saline or cisplatin. All animals were sacrificed for inner ear histopathological findings 21 days after the last injection. A combination of cisplatin administration and electron beam irradiation produced a severe potentiation of the outer hair cell damage with no inner hair cell damage. Therefore, in treatment of head and neck carcinomas, it is important to pay attention to inner ear damage caused by combination therapy of cisplatin and electron beam irradiation which involves the inner ear. PMID- 2102478 TI - Early diagnosis for bone metastasis of breast cancer based on bone metabolism. AB - Bone metabolism was investigated in 152 patients with breast cancer comprising 109 without bone metastasis (negative group), 9 with suspicious bone metastasis (suspicious group) and 34 with bone metastasis (positive group). Bone scintigraphy had high sensitivity (100%) for diagnosis of bone metastasis, but its specificity was 79.8%. The levels of serum calcium corrected by serum albumin (CaC), ionized calcium (CaF) and serum alkaline phosphatase (ALP) were significantly higher in the positive group than in the negative one. Serum osteocalcin (OC) level was significantly higher in the positive and suspicious groups than in the negative group. The level of procollagen Type III N-peptide (PIIINP) was also higher in the positive group than in the other two groups. Microdensitometric parameters (MCI and sigma GS/D) showed significantly lower values in the positive group than in the negative and suspicious groups. Hormone receptors (ER and PgR) status and tumor markers (CEA, TPA, NCC-ST439 and CA15-3) were not related to the presence of bone metastasis. We conclude that repeated measurements of serum CaC, CaF, ALP, OC and PIIINP, and MCI and sigma GS/D are required to predict bone metastasis, and bone scintigraphy to confirm the site of lesion on the bone system and finally X-ray examination to make an exact diagnosis of pathological changes of the bone. PMID- 2102479 TI - Relationship between the regulation of membrane enzyme activities by gangliosides and a possible ganglioside segregation in membrane microdomains. AB - Laser and neutron scattering experiments showed that in mixed micelles of ganglioside GM2 and GT1b, a membrane mimicking system, the segregation of gangliosides may occur spontaneously. Photolabeling experiments using nitrophenylazide containing ganglioside GM1 proved that gangliosides added to cells in culture enter the cell and bind to its membrane as components of microdomains, which specifically interact with a protein of about 30 kDa. This suggests that ganglioside segregation may be a natural phenomenon. Gangliosides when added to granule cells in culture led to increase in protein phosphorylation, the effect exerted being related to the amount of ganglioside molecules inserted stably into the cell lipid layer and an increase of 0.7% of the cell original ganglioside content promoted an increase of 57% in the incorporation of 32P into cell membrane proteins. From the above results a possible relationship between ganglioside segregation and involvement of ganglioside in enzyme activity control is suggested. PMID- 2102480 TI - Transmembrane communication and disease. AB - Many disease affect cell behaviour by an effect at the cell surface, often leading to altered communication across the plasma membrane. Two examples of this from our own work are presented. The first concerns the induction of pores, leading to a breach of insulating properties of the cell membrane, by agents as diverse as certain viruses, bacterial and animal toxins, or immune molecules. In each case, membrane damage can be prevented by divalent cations such as Ca2+ or Zn2+. The second example concerns the effect of stress stimuli on the ability of cells to take up glucose. Different stresses, such as hyperthermia, toxic chemicals or infection by certain viruses, cause cells to increase glucose uptake. As with insulin-stimulated glucose uptake, the mechanism is by translocation of the glucose transporter protein from an intracellular (inactive) site to the plasma membrane. PMID- 2102481 TI - Membrane-associated cytoskeleton and transbilayer phospholipid asymmetry. AB - Earlier studies have suggested that the membrane-associated cytoskeleton (membrane skeleton) in erythrocytes plays a major role in maintaining the transmembrane phospholipid asymmetry. But recently, it has been proposed that an ATP-dependent aminophospholipid pump is the sole determinant of this asymmetry in these cells. A critical analysis of the published data along with some unpublished results from the author's laboratory, however, indicate that both membrane skeleton and ATP-dependent aminophospholipid pump are required for maintaining the membrane phospholipid asymmetry in native erythrocytes. PMID- 2102482 TI - On the carbohydrate binding specificity of lectins: the game is never over. AB - The physiological role of plant lectins still remains a mystery. Nevertheless the carbohydrate binding properties of these proteins are a source of great fascination and have been applied to the study of glycoconjugates on cell surfaces and in solution. These matters are discussed. PMID- 2102483 TI - Liposomal amphotericin-B as a therapeutic measure to control experimental aspergillosis in BALB/c mice. PMID- 2102484 TI - Glycosphingolipids of porcine blood: human blood group A and H antigens with type 1 chain in erythrocytes and plasma. AB - Glycosphingolipids were purified from porcine erythrocytes and plasma. Two minor glycolipids with human blood group A and H antigenicities were found in both sources as components. The two antigenic glycolipids were identified as a hexaglycosylceramide (IV3 alpha GalNAc,IV2 alpha Fuc-Lc4Cer) for the A antigen and pentaglycosylceramide (IV2 alpha Fuc-Lc4Cer) for the H antigen and belonged to lactoseries (type 1 sugar chain) in contrast to those with neolacto core (type 2 sugar chain) in human erythrocytes, thereby endorsing biochemically the previous serological observations that the A antigen on porcine erythrocytes is uptake from plasma, probably the H antigen being the case. In addition to major glycolipids of globoseries in red cells and plasma, a variety of acidic glycolipids including two classes of sulphatides (sulphated galactosylceramide and sulphated lactosylceramide) and five classes of gangliosides (GM3, GD3, GM1, fucosyl GM1 and GD1a) containing N-acetylneuraminic acid and N-glycolylneuraminic acid were obtained from plasma. PMID- 2102485 TI - Characterization of glycosyl phosphatidylinositol lipids of parasitic protozoans: Leishmania mexicana mexicana promastigotes, Trypanosoma cruzi Peru epimastigotes and Tritrichomonas foetus. AB - Glycosyl phosphatidylinositol lipids of cultured L.mex, mexicana LV732 promastigotes, T. cruzi Peru epimastigotes and Tritrichomonas foetus have been isolated and characterized using metabolic labelling and chromatographic and mass spectrometric (MS) techniques. TLC of the unsaponifiable lipid fractions of L. mex. mexicana and T. cruzi obtained from DEAE Sephadex A-25 followed by Iatrobead column chromatography showed three inositol phosphate-containing lipid components. [3H]myo-inositol, [3H]palmitic acid or H3 32PO4 lipid precursors were incorporated into these three lipid components. Fraction 2 (LM2 and TCP-2) comprises inositol phosphate ceramides. The other two fractions appear to contain mono-O-alkyl and di-O-alkyl glycerol inositol phosphates. Lyso-1-O-alkyl phosphatidylinositols could be cleaved by treatment of PI-specific phosphalipase C. The di-O-alkyl-phospho inositols of these parasites being the first dialkylglycerol lipids reported from eukaryotic membranes raises the possibility of chemotherapy for leishmaniasis and trypanosomiasis based upon functional impairment of alkyl ether lipids. Tritrichomonas foetus contains two major glycophosphosphingolipids, designated TF1 and TF2, which are metabolically labelled with [3H]myo-inositol and H3 32PO4. Both lipids contained ceramides. The major ceramide contains the 18:0 and 18:1 bases and 16:0 N-acyl group. The major glycolipid fraction (TF1) contains fucose linked to inositol diphosphate; one of the phosphates being linked to the ceramide moiety, and the other to ethanolamine. TF1 appears to be a novel class of glycophosphosphingolipid, which may be a part of a membrane anchor. PMID- 2102486 TI - Studies on hormonal modulation of asparagine-linked glycoprotein biosynthesis in explant cultures of rat mammary gland. AB - Glucosidase I has been purified to homogeneity and polyclonal antibodies against the enzyme have been prepared. The anti-glucosidase I antibodies recognized a single band of 85 kDa on western blot at a dilution as high as 1:2000 and also inhibited the enzyme activity, suggesting the specificity of the antibodies. Con A-Sepharose binding experiment indicates that this enzyme itself is a high mannose type N-linked glycoprotein. The increase in the electrophoretic mobility of 85 kDa band following digestion with endoglycosidase H and F strengthened this observation. The presence of any O-linked sugar attached covalently to glucosidase I could not be detected by binding assays with O-linkage specific biotinylated lectins. The studies on developmental regulation suggest that the synthesis of glucosidase I is modulated with the ontogeny of the gland. Lactogenic hormones, viz. insulin, hydrocortisone and prolactin, appeared to regulate the synthesis of glucosidase I. The possible role of these hormones in the overall regulation of protein N-glycosylation has been discussed. PMID- 2102487 TI - Glycolipid composition of a mutant cell line of mouse FM3A cells, and the effect of exogenous glycolipids on cell growth. AB - Had-1 isolated from mouse mammary tumour FM3A cells as a non-permissive cell line to Newcastle disease virus infection is deficient in NDV receptors, and galactosylation of the complex type sugar chains of the glycoproteins is extensively reduced compared to FM3A cells. It is also deficient in UDP-galactose transport into Golgi vesicles. The major neutral glycolipids in FM3A is Lac-Cer, whereas, in Had-1 cell, Glc-Cer is the major glycolipid and the concentration of neutral glycolipids is one-tenth as low as that in FM3A. GM3, GD3 and sialyl i- and I-type lactosaminylceramide are the gangliosides present in both FM3A and Had 1, although their presence in both cells is only in traces. Had-1 contains relatively high N-glycolyl-neuraminic acid. Among the several glycolipids tested, Lac-Cer, Gg-4-Cer and Glc-Cer showed inhibitory effect on proliferation of Had-1 cells, but did not show any appreciable effect on that of FM3A cells. Lac-Cer had the most potent inhibitory effect and this inhibitory effect was completely reversible. While mice injected with 5 x 10(6) cells of FM3A died in one month, those injected of Had-1 cells at the same dose survived for more than 6 months. Thus glycolipids on the cell surface play an essential role during cell growth both in vivo and in vitro. PMID- 2102488 TI - Molecular cloning of a membrane bound tyrosine-specific protein kinase from rat spleen. AB - Tyrosine-specific protein phosphorylation is believed to play an important (though poorly understood) role in various cellular functions in many normal and malignant cells. In order to understand the function of tyrosine-specific protein kinases in normal cells, it is necessary, as an initial step, to identify genes (and proteins) for these enzymes. For this purpose cDNA libraries were constructed in plasmid vector pGEM-3Z and lambda gt11 using mRNA from rat spleen. From these cDNA libraries, cDNA clones coding for a src-related tyrosine-specific protein kinase were isolated. The largest clone (L115) was 1.94 kb in size. Various restriction fragments of this clone were subcloned in plasmid vector for sequencing. The complete nucleotide sequence of the largest clone showed an open reading frame coding for a protein of 503 amino acids. The presence of a glycine at position 2 and an arginine at position 7 indicated that this protein is likely to be acylated at glycine 2 and therefore associated with plasma membrane. This gene showed high homology to human and mouse hck and hence it is perhaps the rat homologue of hck. Moderate level of expression of this gene was observed only in the adult rat spleen and not in other tissues. These results suggest that this kinase gene is expressed in a tissue specific manner. PMID- 2102489 TI - Regulation of sialyltransferase activity in intestinal segments of rats. AB - A differential distribution of sialyltransferase (ST) in different regions of intestine has been shown. Jejunum and ileum homogenates from rats showed almost exclusive presence of alpha-2-3 ST (to Gal in Gal beta-1-4GlcNAc and/or to Gal in Gal beta-1-3GalNAc). In contrast, colon homogenates showed the presence of both alpha-2-3 ST (as above) and alpha-2-6 ST. Incubation of intestinal slices in presence of heat-inactivated horse serum (HHS) showed a time- and temperature dependent secretion of soluble ST into the medium. Both jejunum and ileum slices showed high rates of secretion of alpha-2-3 ST. Colon slices, though rich in alpha-2-6 ST, secreted only alpha-2-3 ST. Colchicine, an anti-mitotic drug, injected into rats caused about 10-fold increase of the serum ST level. Jejunum slices from colchicine-treated rats showed an increased secretion of alpha-2-6 ST, suggesting that intestine undergoes a change in the expression of normal secretion of alpha-2-3 ST to a secretion of alpha-2-6 ST. The secretion of ST from incubated intestinal slices was inhibited by heparin. Certain protein factors (anti-proteases) in HHS bind to heparin-sepharose column and these protein factors are responsible for causing the secretion of ST into the medium. It has also been found that a supernatant fraction of the colon homogenate activated ST. Gel chromatography on HPLC produced 3-4 protein fractions from the colon cytosol and one of this fraction bearing high molecular weight proteins produced the maximum activation of ST.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102490 TI - Elucidation of sialyltransferase as a tumour marker. AB - The report describes results of separation of sialyltransferase isoenzymes by electrofocusing plasma from healthy volunteers and patients having different types of malignant tumour. Extensive modification of the technique was adopted in determining enzyme activity, such as elution of gel strips with the buffer pH corresponding to the gel focusing point; assessment of the effect of different pH on endogenous incorporation of radioactivity to desialated fetuin; and quantitative analysis of protein present in each gel band for calculation of enzyme activity. Plasma from normal individuals showed the existence of 5 sialyltransferase isoenzymes at pI 4.8, 5.5, 6.3, 6.8 and 7.5. There were higher isoenzyme activities in plasma samples from patients afflicted with malignancy of lungs and colon in comparison to normal pattern. Endometrial and breast cancer patients also showed elevated levels of the enzyme which could be controlled by surgery and combined therapies with cytotoxic drugs and radiation, respectively. The observations suggest the potential use of sialyltransferase as a tool for tumour diagnosis, and are discussed in relation to prognosis of the disease in the course of therapy. PMID- 2102491 TI - An anorectic proteoglycan of membrane origin. AB - The endogenous substance(s) involved in the regulation of food intake has been isolated from serum, urine and feces. In the present study, a similar type of anorexigenic proteoglycan was isolated from human rat erythrocyte membranes and rat liver membranes. Membranes were suspended in 2.0% deoxycholate and allowed to stand at 25 degrees C for 30 min. The suspension was treated with 5% TCA, supernatant was collected, dialyzed and concentrated. TCA-soluble proteins were fractionated on Sephadex G-150. The active second peak fractions were further purified on DEAE-Sephadex A-25. Biologically active substance reduced the appetite in rats significantly when given intraperitoneally. The proteoglycan (50 kDa) consisted of 70-85% carbohydrate. Similar properties of plasma and membrane anorectic substance further indicated its membrane origin. We believe that this anorectic proteoglycan is anchored to cell membranes and released into the blood circulation to regulate the food intake. PMID- 2102492 TI - Hard times and vulnerable people: initial effects of plant closing on autoworkers' mental health. AB - Large-scale 1987 General Motors plant shutdowns offered an unusual opportunity to study effects of actual and anticipated unemployment on mental health. Workers from four closing and 12 nonclosing plants (Ns = 831 and 766 respectively) were interviewed approximately three months before scheduled plant closings. Dependent variables were baseline frequencies of somatic, depressive, and anxiety symptoms. The quasi-experimental design made it possible to explore systematically the mental health problems of individual autoworkers as a function of their employment status, their demographic characteristics, and the interaction of the two. Three groups were formed by dividing workers at closing plants into those already laid off and those anticipating layoff; the third group consisted of workers in nonclosing plants. Results revealed a pattern of interaction between unemployment and demographic variables, showing differential vulnerability to job loss. Less educated blacks were especially affected; follow-up analyses showed that their more distressed mental health could not be attributed entirely to other, prior stressors. PMID- 2102493 TI - Economic antecedents of mental hospitalization: a nineteenth-century time-series test. AB - More than 100 studies have cited M. Harvey Brenner's (1973) claim that fluctuations in the economy increase the onset of mental illness and thus generate increases in mental hospitalization. Published attempts to replicate Brenner, however, have considered only twentieth-century data. One of Brenner's most memorable claims was that a stable inverse relationship between mental illness and the economy could be seen over a 127-year span beginning in the early nineteenth century. Unfortunately, no research since Brenner's has considered nineteenth-century populations. In this paper we analyze the hypothesis that economic change provokes a substantial fraction of first admissions to mental hospitals. We used admissions registers from the three institutions to construct a data base that approximates a psychiatric case register for a nineteenth century American city from 1881 to 1891. Time-series tests show no support for the "provocation" hypothesis. PMID- 2102494 TI - Effects of social support from various sources on depression in elderly persons. AB - Although global measures of social support demonstrate significant effects on psychological and physical well-being, the differential significance of various support sources is largely unknown. The present study examines differences in the effects of functional expressive support by source on depressive symptoms. This approach is contrasted with network interaction studies of elderly persons, which do not measure functional support but do suggest that friends are distinctly significant. Spouse, friends, and adult children were found to rank in descending order of importance; relatives show no effect. Low support may have stronger effects than unavailability of sources. Effects of supports and stressors are not conditioned by age, sex, or widowhood. Implications of findings and further research needs are discussed. PMID- 2102495 TI - Socioeconomic status differences in vulnerability to undesirable life events. AB - Previous research has documented consistently that persons holding low socioeconomic status (SES) positions are more strongly affected emotionally by undesirable life events than are their higher-status counterparts. Two types of resources have been implicated in this differential vulnerability: financial resources and a broader class of coping resources, including social support and resilient personality characteristics. We present an analysis that disaggregates measure of life events and of SES to identify which events and which components of SES are most important for understanding differential vulnerability. We document that the lower-SES vulnerability persists across all types of personal events. In addition, we find that differential vulnerability is not confined to income but extends to education and occupational status as well. On the basis of these patterns, we conclude that differential vulnerability reflects more than a simple economic reality. Previous research offers speculative evidence that status differences in past and current social environments may explain differential vulnerability, especially through their effects on the socialization of resilient personality characteristics. We propose future research that could help to evaluate the validity of these speculations. PMID- 2102496 TI - Explaining the recent decline in cocaine use among young adults: further evidence that perceived risks and disapproval lead to reduced drug use. AB - This paper explores alternative explanations for the recent sharp decline in cocaine use among high school seniors, using questionnaire data from annual nationwide surveys conducted from 1976 through 1988. Results show important parallels with earlier analyses of the longer-term decline in marijuana use. Although lifestyle factors (e.g., religious commitment, truancy, evenings out for fun and recreation) show strong links with use of marijuana and cocaine, these factors have not developed trends in ways that can account for the declines in use of either drug. Reported availability of either drug has not been reduced. Instead, increases in perceived risks and disapproval appear to have contributed substantially to the recent declines in use of marijuana and cocaine. The findings provide strong support for the use of realistic information about risks and consequences as an important ingredient in efforts to prevent drug use. Coupled with the findings on availability, the results emphasize the importance of efforts to reduce demand (as opposed to supply). PMID- 2102497 TI - The effect of religious concentration and affiliation on county cancer mortality rates. AB - Previous research has documented lower cancer mortality rates among religious groups characterized by doctrinal orthodoxy and behavioral conformity. In addition, there is evidence that the general population in an area with a high concentration of religious participants may experience health benefits resulting from diminished exposure to or increased social disapproval of behaviors related to cancer mortality. This research examines the effect of religious concentration and denominational affiliation on county cancer mortality rates. Our findings suggest that religion has a significant impact on mortality rates for all malignancies combined, for digestive cancer, and for respiratory cancer when we control for demographic, environmental, and regional factors known to affect cancer mortality. These results provide new insight into the relationship between religion and health at the macro or community level and suggest that the influence of religion on social structure warrants further attention. PMID- 2102498 TI - The life cycle of an innovation: adoption versus discontinuation of the fluoride mouth rinse program in schools. AB - Reasons for adoption and for discontinuation of a dental caries prevention innovation (the fluoride mouth rinse program) are examined by using recent theory on decision processes within organizations. Greer's (1977) analysis of three theoretical approaches for the study of innovation adoption--classical, organizational, and political--are used as an organizing framework to analyze these two parts of an overall life cycle for innovations. The results from both descriptive and multivariate analyses support the relevance of "political" and "classical" diffusion models for both adoption and discontinuation. Organizational structure variables--e.g., demographic indicators, administrative structures, and financial measures--show little explanatory strength for either outcome. Both outcomes seem to be dominated by "political" influences from strong interpersonal communications rather than by formal decision-making processes. The results suggest that political contingency theories may explain the processes by which organizations adopt and discontinue innovations, whereas classical diffusion theory explains the content of these processes. PMID- 2102499 TI - Mechanisms of the depolarization and contracture due to Na removal in the circular muscle of the guinea-pig stomach. AB - Verapamil (10(-6) M) significantly reduced a development of the membrane depolarization and the contracture which were induced by Na removal. The fully developed depolarization, after exposure to Na-free solution, was reduced greatly by verapamil, excess Ca (15 mM) or sodium nitroprusside (10(-6) M), but some depolarization still remained. This remaining depolarization was completely blocked by readmission of 10 mM Na to Na-free solution containing verapamil, excess Ca or sodium nitroprusside. However, Mn (1.5 mM) did not block the depolarization due to Na removal and if Mn was present in Na-free solution, readmission of 15 mM Na to Na-free solution was not able to block the depolarization. On the other hand, the contracture due to Na removal was inhibited by addition of Mn (1.5 mM) or sodium nitroprusside (10(-6) M), but partially by addition of verapamil (10(-6) M) or excess Ca, to Na-free solution. These remaining contractures were also abolished by readmission of 10 mM Na to Na free solution containing verapamil or excess Ca. Thus, these results suggest that the depolarization and the contracture due to Na removal are induced by increase in cytoplasmic Ca concentrations through (1): verapamil-sensitive Ca channel, (2): Na-Ca exchange system and (3): some mechanism which is inhibited by sodium nitroprusside. PMID- 2102500 TI - [Responses of muscle strips from the internal anal sphincter in Hirschsprung's disease to drugs and electrical field stimulation]. AB - Responses of isolated muscle strips from the rat and the dog internal anal sphincter (IAS) to drugs and electrical field stimulation (EFS) were investigated in vitro for the purpose of clarifying a manner of neural control of IAS. Also, responses of muscle strips from IAS of the patients with Hirschsprung's disease were compared with those of muscle strips from human control IAS. Muscle strips from the dog and human IAS as normal control showed contractions to norepinephrine (NE), which were abolished in the presence of phentolamine and relaxations to isoproterenol. EFS (less than 1 msec) induced relaxations of the muscle strips. These responses to EFS were not affected by either one of phentolamine, propranolol and atropine but were inhibited by tetrodotoxin. Muscle strips from IAS in Hirschsprung's disease contracted to both NE and EFS, the responses of which were abolished in the presence of phentolamine. But no relaxation to EFS of muscle strips from IAS in Hirschsprung's disease was observed. These findings revealed that normal IAS is pharmacologically innervated by alpha-adrenergic excitatory nerve, beta-adrenergic inhibitory nerve and non adrenergic, non-cholinergic inhibitory nerve and suggested that IAS in Hirschsprung's disease is also affected by alpha-adrenergic excitatory nerve but inhibitory neural control is absent. PMID- 2102501 TI - [Effect of feeding on recording characteristics of electrogastrography (EGG) in normal subjects]. AB - Cutaneous recording of electrogastrography reflects gastric mechanical activity. Epigastric leads are superior in recording characteristics than meso-gastric leads, in fasting state, 3.0 cpm waves dominate EGG recording in fasting state. In this study, we analyzed the EGG recording characteristic after feeding in 10 normal subjects. Though the physical changes of gastric shape and volume after feeding, EGG recording was dominated by 3.0 cpm waves. Epigastric leads are still superior in recording characteristics, amplitude of EGG waves and read-abilities, than meso-gastric leads, after feeding. Amplitude of EGG waves increased after feeding when compared to fasting state, suggesting increased mechanical activity of the stomach. We conclude that epigastric leads are suitable in recording of EGG in fasting and in fed state in normal subjects. This position could be most standard recording leads for EGG in clinical settings. PMID- 2102502 TI - [133Xe (xenon) study of pulmonary ventilation and perfusion with a gamma camera]. AB - Pulmonary ventilation and perfusion on regional level was measured by determining the distribution and elimination of introduced by inhalation 133He-gas, accordingly of intravenously injected 133He-solution. Fifty seven patients 7 to 60 years of age were included in the study, distributed by diagnoses, as follows: pulmonary thromboembolism 24 patients, 16 children with recurrent bronchopneumonia, pneumonia 10, central lung cancer 4, lung echinococcus 2 and one patient with LTE associated with chronic obstructive lung disease. All had ventilatory and subsequent perfusion dynamic scintigraphy. Ventilation was measured by the single breath technique. Perfusion scintigraphy was performed by the foregoing scheme, but by intravenous injection of 133He-solution. The entry, distribution and elimination of 133He-solution. The entry, distribution and elimination of 133He-gas and accordingly 133He-solution were followed up on gamma camera display, and the time of radioactive gas elimination from the lungs was determined. Being practicable and nontraumatic, ventilation and perfusion scintigraphy may be repeated several times. This fact helps to follow up the evolution of the disease and the effect of conservative or surgical treatment. The results give an idea of the topographic and functional diagnosis of lung diseases. PMID- 2102503 TI - [Severe combined trauma and the autotransplantation of splenic tissue]. PMID- 2102504 TI - [The results of the formation of a new anal sphincter by using the mm. graciles in acquired anal incontinence]. AB - The operative method of Pickrell for shaping a new anal sphincter from mm.graciles is described, emphasizing the refinements which the authors have introduced in it. In mobilizing the muscle, fascial fibers are left on both sides of the vascular-nervous bundle. They prevent the latter from overdistension when the muscle turns around the anal canal. Two arcuate lateral sections are made in the perianal area; this is followed by driving a subcutaneous tunnel, but under the perineal raphe and the anococcygeal ligaments. The two muscles are perianally wound each on 360 degrees, whereby m.gracilis dex. is fixed to tub. ossis ischii sin. and m.gracilis sin. is fixed to tub. ossis ischii dex. Before being fixed, the tendon end is inserted in the subperiosteal bone tunnel. When the tendon of the muscle is shorter, it may successfully be elongated by the explantoplast Ampoxen (applied in 3 patients). A total of 16 patients were treated. The result was good in 15 (93.8 per cent) and unsatisfactory in 1 (6.2 per cent). PMID- 2102505 TI - [A giant uterine leiomyofibroma treated surgically]. PMID- 2102506 TI - [A case of a patient with a perforated undifferentiated adenocarcinoma of the ileum complicated by total peritonitis]. PMID- 2102508 TI - [A rare case of mechanical ileus]. PMID- 2102507 TI - [Early adhesive ileus after appendicectomy]. AB - For the period 1980-1988 a total of 5363 patients have been operated at the surgical clinics in the town of Pazardzhik. Early adhesive ileus developed in 13 (0.2 per cent). Intestinal obstruction occurred most frequently after destructive appendicitis (84,6 per cent). In 53.8 per cent of the patients it occurred during the first week after the operation. Conservative treatment was effective in only 2 patients. The other 11 were operated. The case fatality rate was 9.09 per cent. Acute appendicitis usually requires operative treatment both in children and in adults. It keeps on being one of the most important problems of modern surgery, agitating the surgeons all over the world. Appendicitis is called an insidious disease, not only because of the manifold clinical picture, but also because it has a leading position among the causes of the grave surgical complication peritonitis and occupies first place as cause of the severe pathology in the peritoneal cavity--the adhesive disease. Early intestinal obstruction is one of the severe complications following appendicectomy. According to available data in the literature, its incidence is between 0.06 and 0.8 per cent. Most authors consider intestinal obstruction as being early, when developing within three weeks after the operation. PMID- 2102509 TI - [The use of a wound dilator-aspirator in abdominal surgery]. PMID- 2102510 TI - [Some less common potentials in operations to cannulate the cervical segment of the thoracic duct]. PMID- 2102511 TI - [The choice of the vascular approach in hemodialysis patients]. PMID- 2102512 TI - [Extrarenal changes in the isotopic nephrogram of surgical patients with abdominal pathology and the potentials for an erroneous interpretation]. AB - Eighty-three patients with surgical abdominal pathology were included in the study. On the isotopic nephrogram they all had bilateral symmetric and analogous pathologic changes with varying degree of severity. The most common cause of renal function changes in patients with abdominal pathology was the reduced intravascular volume or vascular capacity changes, registered on the isotopic nephrogram with characteristic symmetrical pathologic curves. The sharp renal perfusion decrease, leading to decrease of glomerular filtration and diminution of diuresis explains the bilateral changes in the isotopic nephrogram which most frequently resemble obturation. The curves returned to normal 1 to 2 weeks after the physiologic state of the patients was stabilized, indicating extrarenal origin of the registered changes in the isotopic nephrogram. The latter should carefully be interpreted, in view of the possible influence of it of extrarenal factors. PMID- 2102513 TI - [The radiological study of duodenogastric reflux following surgery for perforated duodenal ulcers]. AB - Radiologic aspiration method (99mTc-bound with EHIDA-148 MBq) was used for quantitation of duodenogastric reflux, 3 months after operations for perforated duodenal ulcers. The patients were divided in three groups of 10 each: gr. II- after simple suturing; gr. III--after truncus vagotomy and Heinecke-Mikulicz pyloroplasty and gr. IV after proximal selective vagotomy and rrhaphy. The results were compared with those in a group of practically healthy patients (gr. I). The radioactivity of the gastric aspirate was measured between the 30. and the 60. min at 15 min interval. It was found that proximal selective vagotomy with rrhaphy had minimal duodenogastric reflux and there was no difference with practically normal subjects. Truncus vagotomy was associated with significant duodenogastric reflux. Similar were the results with simple suturing. PMID- 2102514 TI - [Smooth-muscle sphincteroplasty in constructing a colostomy]. AB - A method is described for producing continent colostomal by smooth-muscle sphincteroplasty. There are variants of operative technique: autogenic smooth muscle intestinal grafting and pediculated plasty. A 10 cm long intestinal segment is split along the free tenia, mucosectomized and wrapped around the precolostomal part of the colon. Essential element of the operation is the 100 per cent stretching of the seromuscular flap when fixed. A tight sphincter-like cuff results. The method is unassociated with specific complications. The first impressions of the sphincteroplasty with encouraging results are recorded. In cases when no sphincter effect was obtained there was inadequacy in some elements of the operation. Then the stoma functions as a conventional one. PMID- 2102515 TI - [Retroperitoneal liposarcoma leading to an emergency surgical intervention (the clinical observation of 3 cases)]. PMID- 2102516 TI - [The current aspects of treating residual choledocholithiasis]. AB - Taking into consideration the seriousness of the problem residual calculosis of the common bile duct, the authors analyse the noninvasive methods of treatment during the past 20-30 years. Available data in the literature are adduced pointing to the importance of endoscopic papillotomy and extraction of the calculi. Indications and contraindications for performing this procedure are defined. The different methods of treatment are evaluated on the basis of a follow up of three patients with residual calculosis of the common bile duct, treated by noninvasive method and the experience of treatment of nine patients with this disease for a period of nine years at the Department of Propedeutics of Surgical Diseases, Medical Academy in Sofia, on the one hand, and the experience with 984 patients in whom endoscopic papillotomy has been performed at the Workers Hospital "Dr. R. Angelov" in Sofia, on the other. Preference is given to endoscopic papillotomy with extraction of the calculi in residual common bile duct calculosis over operative treatment, with observance of definite indications. Excellent results of this therapeutic approach are reported: total percentage of early complications 1.52, late complications 1, ineffectiveness of the method 0.4 and case fatality rate 0.6. Another advantage is the limited contraindications and possibility for operative correction. PMID- 2102517 TI - [Suppurative complications following sternotomy]. AB - For a ten-year period when 366 median sternotomies have been performed, 206 of them in cardiac operations under bypass, there were 15 dehiscences of the sternum (4.09 per cent). The method of early revision with subsequent one-story suture and persistently washing aspiration drainage was applied for treatment of grave complication. In 90 per cent of the patients the causative agent of the infection was Pseudomonas aeruginosa and in the rest--Staph.aureus. Despite the early intervention, the adequate antibacterial therapy and local application of antiseptic agents, mortality was 46.6 per cent. The authors introduced also the so called nodulating sternotomy, which provides firmer fixation. This operation was performed in 135 patients. Rigid septics and antiseptics play crucial role for nonadmission of infection in operations under bypass. PMID- 2102518 TI - [Extracorporeal lithotripsy of kidney and ureteral calculi after open operations]. AB - Experience is recorded with the application of stroke-wave extracorporeal lithotripsy of calculi which have remained after open-technique operations for coral-shaped calculosis. Fifteen patients, 11 women and 4 men at mean age 43 years have been treated for the period 1.01.1989 through 7.02.1990. They all had nephrostoma placed by operation. Extracorporeal lithotripsy (ECL) was performed mean 14 days after the operation. The mean length of stay in hospital was 23 days. All patients were calculi-free 3 months after ECL. It is recommended to place nephrostoma when the kidney has not been fully freed from calculi during operation, to allow further performance of ECL. This helps to achieve quicker and complete removal of calculi from the urinary tract, which in turn contributes to successful of the urinary infection. PMID- 2102519 TI - [The diagnostic and treatment problems in kidney tumors]. AB - Experience is recorded with the diagnosis and treatment of 90 patients with tumors of the kidney and its pyelocalyx system. Of all methods of diagnosis major importance is attached to computer axial tomography. It is emphasized that the approach to the kidney, the type and scope of the operative intervention should depend on the stage of tumor development. For tumors of the pyelocalyx system it is recommended to perform nephroureterectomy, since this approach rules out the hazard of appearance of tumors in the ureter. The presence of isolated metastases is no contraindication for performing nephrectomy. Indications for organ preserving operation should be strictly specified. They should applied in patients with single kidney, patients with bilateral tumors and patients with chronic renal failure. PMID- 2102520 TI - [The diagnostic potentials of computed tomography in abdominal trauma]. AB - Experience is recorded with the application of computer tomography in 16 patients with open and blunt abdominal trauma. In 15 patients (93.7 per cent) the computer tomographic diagnosis matched the clinical and the operative diagnosis. In one injury to the spleen inflicted with a knife and scanty hemoperitoneum scanning gave negative result. It is emphasized that computer tomography is a valuable modern diagnostic method in traumatic injury to the parenchymatous abdominal organs, allowing to determine the nature and degree of the injury and to adopt adequate therapeutic approach. The use of this method is justifiable in severe traumatic injuries, presenting diagnostic difficulties. Absolutely reliable are only the positive results. Computer tomography is a valuable tool of diagnosis for detecting and locating postoperative abdominal complications. Its possibilities in injuries to hollow abdominal organs are at present limited. PMID- 2102521 TI - [Our experience in treating internal biliary fistulae]. PMID- 2102522 TI - [Gastrectomy at the peak of gastric hemorrhage]. AB - Two patients have been operated at the acme of gastric hemorrhage: one of them had disseminated gastric and the other--combination of giant bleeding ulcer with total acute hemorrhagic-erosive gastritis. Gastrectomy was performed. The former patient recovered, the latter died of hemorrhagic shock 36 hours after the operation. Inferences are drawn on the need of emergency fiber gastroscopy for exact diagnosis of the hemorrhage and early operative intervention in an optimal term after the possibilities for nonoperative treatment have been exhausted. Indications are determined for gastrectomy at the acme of the hemorrhage as a radical operation promising a better outlook during the postoperative period. PMID- 2102523 TI - [The endoscopic treatment of large calculi in the choledochus. The preliminary results with intracorporeal electrohydraulic shock-wave lithotripsy]. AB - Results are reported of endoscopic treatment of: 236 patients with common bile duct calculi treated by endoscopic sphincterotomy with or without hydrostatic balloon extraction and extraction of the calculi, mechanical lithotripsy and endoprosthesis; preliminary results in 12 patients treated by intracorporeal electrohydraulic lithotripsy. Complete removal of calculi from the common bile duct was achieved in 171 of 236 sphincterotomized patients (72 per cent). Complications were observed in 11 per cent of the patients. Mechanical cracking of common bile duct calculi was realized in 60 of 65 patients (92 per cent) with complications observed in 3 per cent. Thus, with the use of mechanical lithotripsy the success of endoscopic treatment rose to 98 per cent, without increase in the incidence of complications. Seven patients had endoprostheses placed because of failure to extract the calculi. Intracorporeal electrohydraulic lithotripsy was performed in 12 patients with common bile duct lithiasis (4 with single and 8 with numerous stones with diameter 20-40 mm. In one patient transient acute pancreatitis was observed. A rise in serum amylase content was recorded in 9 patients. The stones in the common bile duct were effectively broken to pieces and removed in 8 patients. Lithotripsy was unsuccessful in 4 patients, two of whom had solid calcium depositions. In the common bile duct of the other two MTBE gas applied. The patients were subjected to repeated lithotripsy with positive effect. It is pointed out in conclusion that crushing stones in the common bile duct allows real improvement of the results of endoscopic sphincterotomy in common bile duct calculosis. Endoscopic treatment of larger calculi became also feasible which until a few years ago were contraindication for endoscopic treatment. PMID- 2102524 TI - [Fracture of the penis]. AB - Fracture of the penis is a rare traumatic lesion with typical clinical symptoms. Six cases treated at the Clinic of Urology in the city of Varna from 1985 through 1989 are presented. Five patients were operated and one patient received conservative treatment. There were no significant complications, except one pseudodiverticulum and one slight deformity of the penis; none of them affected normal sexual activity. A review of the literature is made. Immediate surgical treatment is recommended. PMID- 2102525 TI - [Acute inflammatory diseases of the extremities]. AB - A total of 208 patients with diseases of the extremities, 56 of whom with diabetes mellitus, were included in the study. Septicemia developed in 6 patients, in 4 of them being caused by anaerobic pathogens. The following surgical interventions were performed: 193 incisions, 32 amputations of varying extent and 15 large-scale necrotomies. The case fatality rate was 1.44 per cent. To achieve superior therapeutic results and a better life for patients with diabetes mellitus, it is necessary to change the former approach to their long term medical surveillance. PMID- 2102526 TI - [The indications for surgical methods in treating diseases of the coronary arteries]. AB - Included in the study were 236 operations for ischemic heart disease (IHD) aorto coronary shunt (ACS)--88 patients; ACS + aneurysmectomy--30; ACS + endarterectomy -12, aneurysmectomy--70; skin endocoronary balloon angioplasty--34, heart transplantation--2. The postoperative mortality was 6.5 per cent. Indications for ACS were specified on the basis of the patients state of well-being, the bicycle ergometry [correction of veloergometric] test, the coronarography and ventriculography, the end diastolic pressure and the ejection fraction. Decisive in selecting patients for operative treatment were the data of selective coronarography. PMID- 2102527 TI - [Typhoid-induced intestinal perforations]. PMID- 2102528 TI - [In situ bypass]. PMID- 2102529 TI - [Mucosa-associated lymphoid tissue and its neoplasms]. PMID- 2102530 TI - [The prevalence of Borrelia burgdorferi antibodies in a population at risk]. AB - Given the increasing interest in Lyme borreliosis in our community, and the lack of epidemiological studies in our country, we have considered convenient to analyze the presence of anti-Borrelia burgdorferi antibodies in a group of workmen who we have considered at high risk since they carry out their everyday work in an environment infested by ticks. Significant antibody titers (= or greater than 1/128) are found in 38% of cases versus 0% in the control group. The significance of these results in relation to the presence or not of compatible clinical manifestations and tick bites are studied. PMID- 2102531 TI - [Acute gastroenteritis: a prospective study of 445 cases]. AB - Four hundred and fourty-five adult patients suffering acute gastroenteritis (AG) seen at the emergency ward of two hospitals in Barcelona, have been studied. The aim of this work was to analyze the cause of AG in our community and to evaluate the utility of the biologic and clinical criteria chosen as indicators of bacteremia or of AG produced by invasive microorganisms. Stool culture was positive in 157 patients (35%) of which 140 were Salmonella sp. The most frequently isolated serotype was S. enteritidis. Eight patients (7.8%) presented Salmonella sp. bacteremia. Presence of an underlying disease, dehydration, shivers, fever, presence of occult blood in stools, septic hemogram and the history of AG in other family members were more common in patients with a positive stool culture (p less than 0.05). Patients with bacteremia presented dehydration with a significantly higher frequency than nonbacteremics. The rest of the parameters studied were similar in both groups. We conclude that Salmonella sp. is the most frequently encountered microorganisms responsible for adult AG in our community. It is possible to identify patients with AG due to Salmonella sp. based on clinical and biological parameters. On the contrary, it is necessary to perform a wider study in order to determine the parameters that may allow the identification of patients with bacteremia. PMID- 2102532 TI - [Obesity and arterial hypertension. A cross-sectional study of their prevalence in the population of L'Hospitalet de Llobregat]. AB - A study of the prevalence of arterial hypertension and obesity has been performed in the community of Hospitalet de Llobregat which is an industrial town of 289,000 inhabitants in the vicinity of Barcelona. We have studied a population sample of 801 individuals over the age of 19 years, randomly chosen from the elections lists from 1986, and who were classified according to age and sex. Four hundred and thirty two subjects (54%) had a Quetelet index (QI) of 25 or above. Out of these, 300 (38%) had a QI between 25-30 and 124 (16%) had a QI of 30 or above. Obesity prevalence defined as an QI greater than or = 25 was lower in the youngest group (20-39 years), both in males as in females, with a significant difference p less than 0.05). Arterial hypertension prevalence (SAP greater than 160 and/or DAP greater than 95 mmHg) was 19.8%. When individuals with DAP of 90 94 were included, prevalence was 25.7%. A positive correlation between QI and arterial blood pressure was found in the sample studied as a whole, both for systolic arterial pressure (r = 0.23; p less than 0.001; R2 = 0.053) as for diastolic arterial pressure (r = 0.23; p less than 0.001; R2 = 0.053). Arterial hypertension prevalence (SAP greater than 160 and or DAP greater than 90 mmHg plus those individuals with lower values but were on hypotensive treatment) was higher in obese individuals (QI greater than 25). The difference was statistically significant in males below 60. In females a tendency was observed in women below 40. (p = 0.054).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102534 TI - [The superior vena cava syndrome secondary to a benign intrathoracic goiter: a case report and review of the literature]. AB - The clinical case of a female patient suffering a benign retrosternal goitre which first appeared as a superior vena cava syndrome, is presented. After confirming the diagnosis with an intrathoracic CT scan, a subtotal bilateral thyroidectomy was performed resulting in a complete remission of the clinical picture. A literature review is performed commenting on some clinical, diagnostic and therapeutical aspects. PMID- 2102533 TI - [Community viral pneumonia in the adult population: a prospective multicenter study of 62 cases. The Pneumonia Study Group of the Community of Valencia]. AB - The present work prospectively analyzes, in a multicentric study, viral pneumonias acquired in the community during one year. Were studied 510 patients diagnosed of pneumonia in hospital, or whom 62 (12.1%) had a viral origin. Influenza virus A and B were the most common causative agents (47.6% and 20.6% respectively). Smoking habit was present in 44% of patients, previous OCFA in 45% and other previous pathology in 64.4%. The greatest number of registered cases was during December. The most frequent radiologic finding was alveolar pattern. Evolution in general, was favourable with a low mortality rate (one case). PMID- 2102535 TI - [Primary pulmonary actinomycosis: the experience in a general hospital]. AB - Although all Actinomyces species are capable of producing primary pulmonary pathology, actinomycosis is a rare entity which is infrequently diagnosed. The clinician's lack of knowledge of the disease is frequently blamed for this, and it is estimated that its incidence in our environment is greater than suspected. We present our experience consisting of four cases of primary pulmonary actinomycosis (PPA) diagnosed at La Paz Hospital from 1974 to 1988. Its particular characteristics are emphasized as well as the need to include it in the differential diagnosis of chronic pulmonary infiltrations, cavitated lesions or pulmonary masses. PMID- 2102536 TI - [Dysphagia as the form of presentation of Forestier-Rotes disease]. AB - We present the case of a 73-year-old patient suffering dysphagia secondary to cervical osteophytosis as the clinical presentation of Forestier-Rotes disease. Although this is a frequent disease, there are few cases of dysphagia secondary to this condition it being the initial symptom exceptional. The diagnostic methodology is commented emphasizing cervical CT scan as well as the therapeutic attitude, suggesting starting with a conservative treatment since surgery is not always successful. PMID- 2102537 TI - [The influence of attending theory classes and other factors on the academic performance of undergraduate surgery students]. AB - The authors have studied the influence of the academic history, class attendance, and use of commission notes on the student's academic performance, evaluated by the final marks, on a population of 335 sixth year students taking a surgical pathology course at the School of Medicine. The results show that previous marks correlate with the final surgery mark, that class attendance does not determine significant differences in the student's performance, and that the use of commission notes is widely spread conditioning a mediocre undergraduate [correction of pregraduate] theoretical education [correction of formation]. PMID- 2102538 TI - [Vaccines against the hepatitis B virus. The outstanding problems]. PMID- 2102539 TI - [A 60-year-old man with a palpable abdominal mass and constipation]. PMID- 2102540 TI - [The null prevalence of unsuspected HIV infection in a hospital emergency service]. PMID- 2102541 TI - [The hypolipemic effect of cimetidine]. PMID- 2102542 TI - [Serum BCM in patients with nontumorous diseases. Preliminary results]. PMID- 2102543 TI - [Sepsis due to Streptococcus zooepidemicus]. PMID- 2102544 TI - [Boutonneuse fever from Kruger Park]. PMID- 2102545 TI - [Terminal aortic embolism as an unusual form of presentation of apical hypertrophy]. PMID- 2102546 TI - [Luetic meningitis: an atypical form of presentation simulating a pseudomigraine with inflammatory CSF]. PMID- 2102547 TI - Magnetotaxis. AB - The ability of magnetotactic bacteria to orientate and navigate along geomagnetic lines is due to intracellular magnetic particles. These are enclosed within a membrane to form a magnetosome, a specialized organelle of magnetotactic organisms. The magnetic crystallite of many of the magnetotactic bacteria and algae is the iron oxide magnetite (Fe3O4) but recently a multicellular bacterial aggregate has been found to contain magnetic iron sulphide. Magnetotactic bacteria are found in regions of low oxygen pressure. Those of the Northern hemisphere are north-seeking while those of the Southern hemisphere are south seeking. The opposite polarity of their internal magnets enables both types to travel to the deeper, less oxygenated, regions of their aqueous environments. PMID- 2102548 TI - [Prospective study of the incidence of HIV infection in the 1st trimester of pregnancy]. AB - The article deals with the results of an anonymous testing of HIV infections in Yugoslavia. The presence of anti-HIV-antibodies was examined in the blood of pregnant patients, randomly selected, in a Ward where about 3000 artificial abortions were carried out in the first trimester of pregnancy in a six-month period. On the basis of the obtained results one patient of 177 tested women was infected by HIV virus. At the same time, it can be presumed that among 3000 pregnancies there were many anti-HIV positive persons. It should be emphasized that the staff was not aware of HIV infection in one patient, and that in Yugoslav epidemiological conditions a HIV infected person could unexpectedly be detected without preliminary findings and data. PMID- 2102550 TI - [Diurnal rhythm and the effect of hemodialysis therapy on blood prolactin levels in patients with chronic renal insufficiency]. AB - In 97 patients with different stages of chronic renal failure prolactin serum level was determined, and its diurnal rhythm and dependence on haemodialysis treatment were studied. Diurnal rhythm was investigated in 6 men and 6 women with advanced chronic renal failure on diet and other symptomatic treatment. A normal diurnal rhythm of prolactin was recorded only in 3 patients, two of them being with elevated basal prolactin levels; an abnormal prolactin rhythm was documented in 8 patients. In 4 patients no evident diurnal changes in prolactin level were observed, though 3 of them had a normal basal prolactin level. In one patient slight fluctuations of the prolactin level were recorded, while in 4 other patients an abnormal type of diurnal rhythm was observed. Prolactin determinations in patients on maintenance haemodialysis showed increased values in 45 men (719 + 122 mIU/l) as well as 34 women (1251 + 171 mIU/l). The analysis of the influence of haemodialysis on cuprophane and polyacrylonitrile membrane was made in 6 patients and no difference was shown between predialysis and postdialysis serum prolactin values, as well as in values obtained for non dialysis and dialysis days. The results obtained in this study showed an absent or abnormal diurnal rhythm of prolactin in 75% of patients with chronic renal failure. In patients on maintenance haemodialysis increased prolactin levels were found. Haemodialysis procedure on cuprophane and polyacrylonitrile membrane failed to affect the serum level of prolactin. PMID- 2102549 TI - [The effect of desferrioxamine in aluminum-processing workers]. AB - The presence of aluminium, iron, copper, zinc and manganum was evaluated in workers who were professionally exposed to aeropollution, especially to metals i.e. aluminium (n = 25) and workers who were not exposed to toxic noxe (= 18). The instantaneous presence of metal concentrations in the blood and urine was not a sufficient sign in the evaluation of the body burden. The intramuscular administration of desferrioxamine had a significant effect on the mobilization of iron- and aluminium-depots. On the basis of increased aluminium elimination, changed values of total transferrin (TIBC) and increased activity of alkaline phosphatase in the serum provoked by desferrioxamine it was possible to evaluate the presence of aluminium in exposed workers. According to the obtained results desferrioxamine had no effect on copper, zinc and manganum in the organism of these workers. PMID- 2102551 TI - [Serum gastrin in patients with diabetes]. AB - We evaluated the basal and postprandial circulating levels of gastrin in 20 diabetic patients and in 20 normal subject. The basal gastrin concentrations were not statistically different in comparison to controls. The blood tests provoked increased circulating levels of gastrin. In our study diabetes significantly enhanced that response, particularly in diabetics with severe disease, peripheral neuropathy and in untreated patients. Histologic evidence of antral hyperplasia was obtained in 7 patients; atrophic gastritis and intestinal metaplasia were found in 3 diabetics. We postulate that postprandial gastrin levels raised secondary to achlorhydria, common in diabetics. PMID- 2102552 TI - [Status epilepticus: retrospective analysis of clinical characteristics over a 5 year period]. AB - Clinical features of status epilepticus (SE) were analysed retrospectively in a five-year period. Among 55 patients there were 65 episodes of SE, most frequently of generalised tonic-clonic type. There were also 7 episodes of simple motor, 5 of complex partial, 1 of petit mal and 4 of nonconvulsive "electric" SE. Seventy five percent of patients with initial SE had organic brain disease as an underlying cause versus 14% of patients with intercurrent SE (p = 0.002). The most frequent precipitating factor in the group of intercurrent status epilepticus was erroneous antiepileptic drug treatment. Median duration of SE in the group with idiopathic causes was 5.5, in the group with acute symptomatic causes 6.5, in the group with chronic symptomatic causes 14, in the group of fatal cases 5, and in the whole group 10.5 hours (p0.05). Most of this time (30% to 98% of the whole time, median value 79%) elapsed before admission to the Department, showing poor prehospital management. Termination of SE was accomplished with standard treatment (intravenous diazepam and intramuscular phenobarbital) in 47 cases within 30 minutes, while the others required additional treatment. Due to the underlying diseases there were 6 fatal cases (9.2%), 2 during uninterrupted SE and 4 after the seizure abolishion. There was no neurological or intellectual deterioration after the termination of SE, that could be attributed to detrimental effects of SE per se. Finally, the description of 5 cases of complex partial SE is included. These results were also compared to other research results as presented in several recent references. PMID- 2102553 TI - [Characteristics of suicide after committing homicide]. AB - The article deals with autopsy material from the Institute of Forensic Medicine in Belgrade related to murder and suicide, when the person who committed suicide was previously the person who committed murder. The material covers the period from 1926 to 1975. There were 79 cases when after committed murder of multiple murders, or attempted murder, this person committed suicide. The motives for committing suicide were some what the same as those for committing murder. In some cases motives for committing suicide existed before murder. In the others, however, these motives were related to murder. The victim had a dominant role in the formation of motives of suicide, but also in the formation of motives that made this person victim. PMID- 2102554 TI - [Intrathecal synthesis of immunoglobulins during acute viral meningitis with high cerebrospinal fluid protein levels]. AB - The article deals with the results of examination of immunoglobulins (IgM, IgA, IgG) in the liquor and serum of 50 patients with acute viral meningitis and hyperproterinorashia over 1.0 g/l. The quantitative determination of immunoglobulins was done by the method of radial immunodiffusion according to Manzoni. The confirmation of intrathecal synthesis of immunoglobulins was done by liquor indexes. IGM intrathecal synthesis was found in 11 (22%) patients, IgA in 16 (32%) and IgG in 10 (20%) subjects. The daily amount of IgG synthesis in the central nervous system was 1.65-97.15 mg (mean 26.60 mg). The values of liquor indexes were decreased in later disease. This suggested the decrease of disappearance of immunoglobulin intrathecal synthesis. There were 26 control patients with meningism (meningeal syndrome with regular cytobiochemical finding in the liquor). IgG intrathecal synthesis was established in one patient with meningism. This finding was an extremely rare and unusual finding. PMID- 2102556 TI - [Epidemiologic characteristics of streptococcal pharyngitis, scarlatina and rheumatic fever in the area of Belgrade 1981-1987]. AB - The paper deals with the epidemiological data on streptococcal diseases (pharyngitis, scarlet fever and rheumatic fever) over the period from 1981-1987. The results of epidemiological investigations revealed a continuous decrease of rheumatic fever in the population, aged from 0 to 19 years. The maximum mortality rate of streptococcal diseases was registered in 1982 with 4,259.59 cases of streptococcal pharyngitis, 544.08 cases of scarlet fever and 9.17 of rheumatic fever on 100,000 inhabitants. The minimum morbidity rate for rheumatic fever was registered in 1987 (3,31%). Over the period from 1976-1987 the morbidity rate of rheumatic fever was twice and four times decreased in the Belgrade population, aged 0-19 years. According to the conclusions of the Vith Republican Meeting on Rheumatic Fever (Belgrade, 1980) a success in primary prophylaxis of rheumatic fever was achieved. But, there are still some questions without answer, as for instance, what is the relation between the carrier and the risk of rheumatic fever; why the human alone is susceptible to rheumatic fever; is the immunisation a future alternative approach, ets. In view of current epidemiological data on rheumatic fever in the world, it is necessary to start with a longterm prospective epidemiological study to determine the prevalent M-types of group A streptococci directly related to rheumatic fever. PMID- 2102555 TI - [Evaluation of insulin sensitivity in diabetes using the euglycemic hyperinsulinemic clamp method]. AB - Assessment of peripheral insulin sensitivity using artificial endocrine pancreas was done in 15 diabetics (6 with insulin dependent diabetes mellitus and 9 with non-insulin dependent diabetes mellitus) and in 10 healthy controls, matched for sex, age and body mass index. Insulin sensitivity-RC was expressed in mg of utilised glucose/kg body weight in minute. Significantly lower insulin sensitivity was found in non-insulin dependent diabetes mellitus (RC = 2.30 +/- 1.37) compared to insulin dependent group (RC = 5.88 +/- 2.89) and control group (RC = 4.93 +/- 1.96). There was no significant change in insulin sensitivity between insulin dependent diabetics and controls (p greater than 0.05). It is concluded that investigations of this kind could be used in search for pathogenetic mechanism of insulin resistance in some types of diabetes mellitus on one side, and on the other side that euglycemic clamp technique could be used for the assessment of the effects of some therapeutical measures on peripheral insulin sensitivity. PMID- 2102557 TI - [Injuries of the ossicular chain in head injuries]. PMID- 2102558 TI - [Tuberculosis infection as an etiologic factor in acute renal insufficiency]. AB - The article deals with a retrospective study of patients treated in the Institute over the period from 1980 to 1984 for acute renal insufficiency caused by tuberculous infection, as well as with the results of control examinations of the renal function in these patients from 5-49 months after the onset of the disease. The creatinine clearance under 10 ml/min was registered in 6 of 9 patients on admission. Recovery of the renal function was noted in 8 patients. The ninth patient, with unchanged terminal insufficiency had also pulmonary and extrapulmonary tuberculosis (lymphatic glands and kidneys). The treatment depended on the degree of the damaged renal function (conservative therapy or active treatment-dialysis). The follow-up of these patients revealed an increase of creatinine clearance (84.22 +/- 14.43 ml/min) in comparison to the result on dismissal from hospital (71 +/- 37.79 ml/min). PMID- 2102559 TI - [IgA nephropathy]. AB - A great interest in IgA nephropathy was demonstrated in the last few years. Unfortunately, a complete picture of this chronic disease should not yet been made. The article deals with 7 patients with IgA nephropathy treated in our Institute. The following characteristics were examined during a long period of time (1-17 years): clinical picture, course of the disease, clinical and morphologic correlations. The disease is characterised by micro-and macro haematuria. In 6 patients a moderate proteinuria and slow progression of the disease were noted. Hypertension, massive proteinuria and azothemia in IgA nephropathy suggested a bad prognosis of the disease. This was confirmed in one patient who developed terminal renal insufficiency within 4 months. The pathological finding by optic microscope revealed a wide spectrum of changes. The role of immunofluorescent microscopy is crucial in the diagnosis of this disease. PMID- 2102560 TI - [Etiopathogenesis of the inflammation process and the incidence of urinary tract infections]. AB - Etiopathogenesis of inflammatory processes of the urinary tract, mainly of obstructive uropathy and chronic pyelonephritis, is reviewed. The most frequent cause of obstruction is renal calculosis; in the pathogenesis of chronic pyelonephritis the following factors are of great importance: renal and urethral anomalies, renal stones, pregnancy, bladder instrumentation as catheterisation, etc. We analyzed 2101 random by selected hospital patients and found significant bacteriuria in 740 (35 p.c.) of them. The most frequent cultured bacteria which caused urinary infection were: Proteus strains (29.3 p.c), E. coli (27.5 p.c.) and Pseudomonas aerug. (13,6 p.c.) Significant bacteriuria was more frequent in men than in women, but E. coli was more frequent in women (71.5 p.c.). Proteus, Pseudomonas and Klebsiella were more frequent in men. It should be noted that the majority of patients with positive urinary cultures were subjects treated at the Urology Department; and that men prevailed. This is the reason why our results related to the causing bacteria differed from those found in general population. PMID- 2102561 TI - [The foundations of Serbian medical historiography]. PMID- 2102562 TI - Japanese dietary intake of salt and protein--relating to the strategy of salt restriction. AB - The high level of Japanese salt intake, which has been the major risk factor for cerebrovascular disease and hypertension, has decreased since World War II, and reached a steady level. In the present study, the dietary salt intake in Tohoku (once the district of highest sodium intake) and that in Kyushu (once the district of median or low sodium intake) were studied in relation to nutritional status by the analysis of sodium and urea-nitrogen excretion in 24-hr urine samples collected from 305 healthy Japanese. When the amount of urinary creatinine and urea-nitrogen were adjusted, the mean value of urinary sodium in females was significantly larger in Tohoku than in Kyushu, but not significantly in males. The regional difference of salt intake still remains, although it seems to be disappearing. Traditionally, Japanese high intake of salt was accompanied by poor nutritional status. In the present study, however, a significant positive correlation was observed between sodium and urea-nitrogen. The excess of protein intake would cause the excess of salt intake. Therefore, the strategy of further salt restriction should be directed to not only traditional salty foods but also nutritional status such as protein intake. PMID- 2102563 TI - Permanent brain damage possibly caused by theophylline in two elderly patients with airway obstruction. AB - Two aged patients with bronchial asthma and chronic obstructive pulmonary disease who suffered convulsions that resulted in permanent brain damage during treatment with the recommended therapeutic dose of theophylline are presented here. A dose or concentration of theophylline lower than the recommended one should be considered in the treatment of some aged patients with pulmonary obstructive disease. PMID- 2102564 TI - Epithelial cell clusters of distal convoluted tubules in end-stage chronic glomerulonephritis. AB - Differences in the pathologic changes of the proximal convoluted tubules, the cortical segments of the thick ascending limbs of the loops of Henle, and the distal convoluted tubules in the end-stage kidneys with chronic glomerulonephritis were studied by means of both light and electron microscopy. Kidneys with chronic glomerulonephritis were obtained from 8 non-dialyzed patients at autopsy and 9 dialyzed patients at the time of nephrectomy prior to renal transplantation. Epithelial cell clusters with clear cytoplasm, decreases in the luminal and outer diameters of the tubules, and thin basement membranes were observed in both the non-dialyzed and dialyzed kidneys to varying degrees. The epithelial cell clusters were more extensive and distinct in kidneys from patients with a long history of chronic glomerulonephritis and/or long-term hemodialysis. Electron microscopy of the epithelial cell clusters revealed the absence or narrowing of lumens and luminal surfaces that were smooth except for a few short microvilli. Observation of serial sections showed that these epithelial cell clusters were derived from the distal convoluted tubules belonging to obsolescent glomeruli. This form of tubular change is quite different from the well-known atrophy of the proximal convoluted tubules belonging to obsolescent glomeruli in chronic glomerulonephritis. PMID- 2102565 TI - Determinants of maximum walking speed in hemiparetic stroke patients. AB - The time necessary to walk 10 m with the fastest speed, the sway path of the center of feet pressure in station, and the isokinetic strength for knee extension of each side were examined in 29 hemiparetic stroke patients. The maximum walking speed of the patients was related to the sway path and the isokinetic muscle strength of affected side. The patients could be divided into two groups based on their sway path. The determinants of the maximum walking speed in the unstable group were the sway path and the isokinetic muscle strength of the both sides, whereas that in the stable group was only the isokinetic muscle strength of affected side. PMID- 2102566 TI - Prolonged hypoxemia after 10 min walking exercise in aged patients with chronic obstructive pulmonary disease. AB - Although the behavior and factors of exercise tolerance have been studied during exercise in patients with chronic obstructive pulmonary disease (COPD), little attention has been paid to the after-effects of such activity. Arterial oxygen saturation (SaO2) was monitored during and after a 10 min walking exercise in aged patients with COPD. Neither baseline SaO2 nor mean SaO2 during exercise correlated to the 10 min walking distance. However, the recovery time of SaO2 to the baseline value shows significant correlation to the 10 min walking distance. Careful attention should be paid to prolonged hypoxemia after exercise in severe cases of COPD. PMID- 2102567 TI - Multiple myeloma associated with amyloidosis and t(1;20)(q21;q11) translocation. AB - A 59-year-old woman with nephrotic syndrome was diagnosed as having primary amyloidosis based on the detection of amyloid deposition (AL-protein) in the esophagus and kidneys. Bone marrow aspirate showed plasmocytic proliferation, leading to a diagnosis of multiple myeloma (IgG lambda-type). In addition, a very rare translocation t(1; 20) (q21; q11) was seen by chromosomal analysis of both the bone marrow and peripheral blood. PMID- 2102568 TI - Ultraviolet-B phototest in patients with atopic dermatitis. AB - To evaluate the possibility of ultraviolet (UV) rays as an aggravating factor of atopic dermatitis (AD), UV-B phototest was performed in patients with AD. Resulting, minimal erythema doses for UV-B were all within normal range and AD lesions were not reproduced by irradiation. UV-B may not be an important factor for skin aggravation in patients with AD. PMID- 2102569 TI - [Allergic and serologic diagnosis of paratuberculosis in cattle]. AB - The use of allergenodiagnosis in cattle herds where paratuberculosis is to be eradicated depends on the allergenogenic properties of the causative agent of this disease. An evaluation of the reliability of an intradermal allergic test performed to diagnose paratuberculosis in cattle in the given area revealed that this method is important especially if the result of this test is explicitly negative. A cultivation proof of the causative agent of paratuberculosis is of greatest importance among bacteriological methods for infection diagnosis. The agreement of the bacteriological and serological examination which reached 80% in young cattle pointed out the high specificity of an indirect haemagglutination test. In cows, unlike calves and heifers, the specificity of diagnostic tests was considerably lower. It is recommended to use an elimination method mainly in young cattle: regular examinations of calves from their age of three months will help to form a group of heifers free of infection, observing the basic infection controlling measures and providing conventient diet. PMID- 2102570 TI - [The embryo yield in relation to the method of processing the irrigation fluid in superovulated donor cows]. AB - Total 240 flushings of superovulated donor cows were examined after double sedimentation. Altogether 2,810 ova and embryos, i.e. average of 11.7 per donor, including 9.0 (76.97%) transferable embryos, were obtained after the first sedimentation. The sedimentation was carried out separately for the respective uterine horns. The second sedimentation, which was carried out in the flushing from both uterine horns simultaneously, yielded ova and embryos in 82.9% (199/240) of the cases. Total 679 ova and embryos were found, i.e. 3.41 per donor, including 2.61 (76.58%) transferable embryos per donor. The increase of the yield of total ova and embryos, and transferable embryos, was 2.82 and 2.16 (24:16 and 24.04%) respectively after the second sedimentation. Altogether 3.489 total ova and embryos were obtained from 240 donors. The average embryo yield was 14.53 per donor with 76.89% (11.17) transferable embryos. The embryo yield/corpora lutea ratio was at the number of corpora lutea 12.04 on the average 120.68%. It is concluded that the second sedimentation of the flushing provides for the release of a part of the embryos for the mucous and cell aggregations, which density is usually lower. The effect of the second sedimentation is considerable, because as much as 24% of the total number of transferable embryos can be saved. The total efficiency of superovulation may be considerably decreased if no attention is paid to the above mentioned facts. PMID- 2102571 TI - [Experimental trichophytosis in calves caused by cultures of Trichophyton verrucosum and Trichophyton equinum]. AB - Tests were performed on 130 one-month-old calves. In 16 animals, treatment with a suspension of Trichophyton verrucosum culture at the dosage of 5 mil. conidia for an area of 10 x 10 of the clipped skin caused clinical trichophytic changes. The length of the incubation time was shorter in the calves scarified before inoculation of the infecting culture (10 to 13 days), as compared with the group of calves without scarification of the skin (11 to 19 days). Only 3 in 6 calves, infected by the same dose into non clipped skin, did contract trichophytosis, manifesting themselves as separate mycotic deposits, which appeared 26 to 35 days after inoculation. Trichophytic changes lasted longest in the group with scarification of the infected area. The ID50 in T. verrucosum and T. equinum cultures was about 1500 conidia per one calf in the case of the method of infecting into clipped scarified skin (area 100 sq cm). A 10 times lower dose (150 conidia per one calf) of the T. verrucosum suspension did not induce visible mycotic changes, but the T. equinum inoculation produced infection in one of 10 calves. PMID- 2102572 TI - [Care of animals with rumen fistulas]. AB - The occurrence of post-operative complications and utilization of animals with ruminal fistulas depends on observance of certain principles during the post operative care. These vary according to time periods which elapsed from the operation. In the paper we describe also the processes of change of the two types of fistulas. PMID- 2102573 TI - [Morphogenesis of the cerebral fissures in sheep]. AB - The author studies the development and formation of the boundary fissures in the brains of the foetuses of sheep during their embryonal development from a vertex to-coccyx length (VC length) of 38 mm (39th to 40th day) to birth. The marginal fissures of the cerebral hemispheres were found to develop first. The sulcus hippocami develops from them at a VC length of 46 to 48 mm (42nd to 45th day) and is one of the fissures with a constant course of formation. Sulcus rhinalis lateralis develops from a VC length of 70 to 72 mm (49th to 50th day). The caudal part of this fissure is deeper during the whole prenatal development than the rostral part. PMID- 2102574 TI - [Changes in blood levels of glucose and lactic acid in pregnant sows and fetuses and in sows and piglets 10 days after parturition]. AB - In three series of experiments the variations of lactic acid and glucose concentrations were investigated in pregnant sows, crossbreds of the Large White and Landrace breeds, and in their foetuses on the 104th and 113th day of pregnancy, then in farrowing sows of the same breed and their piglets at delivery (birth) and till the 10th day after birth. In nonpregnant sows the value of lactacidaemia is 1.60 +/- 0.08 mmol per 1. In the first twenty days of pregnancy it increases to 2.50 +/- 0.95 mmol per 1 (p less than 0.05). In the following days of pregnancy until the 81st to 100th day the value ranges from 1.5 to 1.7 mmol per 1. In the last twenty days of pregnancy it increases slightly to 2.10 +/ 0.25 mmol per 1. On the 104th and 113th day the values of lactacidaemia in foetuses in vena and arteria umbilicalis make 7.40 +/- 0.41 and 6.80 +/- 0.37, or 8.50 +/- 0.43 and 8.16 +/- 0.21 mmol per 1, respectively. Glucosaemia values are decreasing in pregnant sows in the first forty days, in the following period of pregnancy they are increasing and on the 101st to 120th day of pregnancy they make 5.39 +/- 0.26 mmol per 1. The foetus to dam ratio lactic acid concentrations is 2.3 and 2.1, respectively, on the 104th and 113th days. Lactacidaemia is highest in farrowing sows (3.15 +/- 0.19 mmol per 1), then there is a statistically significant decrease in the value of this characteristic, and on the day after delivery it makes 2.38 +/- 0.66 mmol per 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102575 TI - [Fertilizing capability of breeding boars by evaluation of the early pregnancy factor in test sows]. AB - The fertilizing ability of breeding boars was evaluated on the basis of an early pregnancy factor (EPF) determined in the blood serum of test sows by the method of rosette inhibition. The fertilizing ability was tested in ten boars on an insemination farm: the fertilizing potency of 41 ejaculates was evaluated from the percent conception of 105 test sows. The percent conception of test sows was evaluated from the EPF positive findings in the blood serum of these sows in the average range of 8.02 +/- 1.70 days (the range of 2 to 11 days) after insemination and from the recorded deliveries. The evaluation of the fertilizing of boars on the basis of EPF in test sows revealed in most cases the higher fertilization rate than could be found on the basis of the recorded deliveries of test sows. There was an exception to this trend: one breeding boar with a paradoxical finding of the somewhat higher percentage of deliveries recorder in test sows, in comparison with the fertilization ability according to the results of EPF. Identical results of the two criteria of fertilizing ability were recorder in another boar with a small number of tested ejaculates and test sows. The average fertilization of the whole set of the breeding boars, expressed by the average percent conception of all test sows, reached 86.67% on the basis of the EPF positive findings in 2 to 11 days after insemination, and 67.31% on the basis of recorded deliveries. These differences in fertilization are likely to be related to the share of dams and can be ascribed to embryonic mortality. PMID- 2102576 TI - [Verification of the hepatoprotective and therapeutic effect of silymarin in experimental liver injury with tetrachloromethane in dogs]. AB - The efficiency of preventive administration of silymarin and of silymarin medication were tested in dogs suffering from CCl4 intoxication of liver. Sixteen dogs of the Beagle breed at the age of 8 to 10 months and of the weight 11.5 to 14.0 kg were divided into four groups with four animals each. Those groups were administered per os a single dose of CCl4, 0.35 ml per kg liveweight contained in sunflower oil. The intact control groups was given sunflower oil free of any additive. Silymarin was administered per os in the form of suspension in the Dorfman reagent twice a day at the dose of 100 mg per kg. Silymarin was administered to the animals of the treated group four days after intoxication, to those of the preventively treated group four days before intoxication. The intact control group and the CCl4 intoxicated control were administered the pure Dorfman reagent. Pure CCl4 induced a significant increase in the AST and ALT activity in 12 and 24 hours after administration, and histological lesions in the liver- vacuolization of hepatocytes and necrobiosis of nuclei. The curative effects of silymarin on these changes were low. The protective effects of silymarin were manifested by the significantly lower AST and ALT activities in the 12th and 24th hour of the trial and by the insignificantly lower extent of lesions in liver parenchyma if compared with the control CCl4 intoxicated group. PMID- 2102577 TI - [The effect of terguride on contractility of rat uterine strips]. AB - The effects of terguride on the uterotonic activity of rat's uterine stria were investigated by means of a standardized isometric method of measuring in vitro the contractility of uterine muscles. The uterotonic activity of the given preparation depends on its concentration and on the phase of uterine cycle. The uterotonic activity makes 71.4 U.mg-1 in the range of terguride concentrations from 10(-7) to 10(-5) mg per ml. Used at higher concentrations, the uterotonic activity of terguride is very low. Spontaneous contractions are moderated and the tone of uterus is decreased by terguride administration. PMID- 2102578 TI - [Fistulization of the rumen in cattle]. AB - Various surgical techniques and two types of fistulas were tested when they were installed (Firm and PVC rumen cannulas were applied in 35 and 12 animals). We consider that the simplest process of installing the fixed rumen fistula is the total resection of abdominal wall together with peritoneum and following fixation of rumen to the abdominal wall with knot stitches and with removal of rumen wall between the stitches in the shape of circle. This process can be mastered by two people without particular equipment in approx. 30. minutes. When installing the PVC fistulas we prefer their fixation in rumen with help of seromuscular circular stitches followed by leading out the fistula off the main cut. PMID- 2102579 TI - [Levels of toxic elements--Cd, Pb, Hg, Cr, Cu, Zn--in the blood and placenta of cows during parturition and in newborn calves]. AB - It was demonstrated that mother's blood and the blood of new-born calves were contaminated by toxic elements in exposed and non-exposed area. The average Cd and Zn levels differed at high statistical significance (P less than 0.01) in the mothers blood from non-exposed regions in comparison with the average Cd and Zn levels from exposed region. The average residues of toxic elements in breeding cows placenta from the exposed and non-exposed regions were not statistically different. The average Zn content in new-born calves from non-exposed regions differ highly statistically significantly in comparison with the average Zn content in the blood of new-born calves from heifers of the exposed region. The transplacental ratio (TPx) of a toxic element in cow placenta during parturition was expressed from the average ratio of toxic element content in mother's blood: toxic element content in placenta: the toxic element content in blood of newborn calf, while the content of toxic element in mother's blood during parturition was expressed by a value equal to one. TPx in parturition period was expressed by mathematical formula TPx = 1 : Xp : Xk, where Xp = toxic element content in placenta, Xk = content of the toxic element in blood of new-born calf. TPPb, Hg, Cr, Cu, Zn values were not statistically different between the groups of breeding cows from exposed and non-exposed regions. TPCd in the group comprising 14 first calves from the exposed region (TPCd = 1:0.89:2.59 in comparison with TPCd of six cows from non-exposed region, where TPCd = 1:0.29: 0.70;, differed statistically highly significantly (P less than .01). High statistical differences (P, less than 01) TPCd between these groups were explicitly affected highly statistically significantly (P less than .01) by different average Cd content in the blood of fourteen first-calves, compared with the average Cd content in blood of six cows from non-exposed region, in which the Cd value in blood during parturition was higher by 10(-1). PMID- 2102580 TI - [Prevention of anestrus in sows after the 1st and 2d parturition]. AB - The procedure of prevention of anoestria after the weaning of piglets was verified in 389 experimental and 332 control sows of the Prestice breed. The set of animals under study included 77 experimental and 122 control primiparae, 68 experimental and 71 control secundiparae, and 244 experimental and 139 control multiparae (i.e. sows with three or more parturitions). The experimental sows were treated with 1000 IU of serum gonadotropin ad usum vet.-Bioveta-(PMSG) the first day after the weaning of piglets and with 300 IU of chorion gonadotropin (HCG) in the Praedyn inj. Spofa preparation together with 1 ml of Dirigestran inj. Spofa (40 micrograms LHRH) 72 hours later. Control sows were not treated with hormones. The treated primiparae and secundiparae respectively, had a significantly higher percentage of oestrus onset within 10 days after weaning and lower occurrence of anoestria over 10 days after weaning by 31.25 per cent (P less than 0.001), and 21.36 per cent (P less than 0.02) respectively as compared with untreated controls. In the set of secundiparae, the studied hormonal treatment speeded oestrus onset by a significant (P less than 0.01) shortening of the interval from weaning to the first insemination by 0.79 day and by a more frequent onset of oestrus within only 5 days after weaning of piglets. The values of the other criteria of reproduction studies, i.e. percentage of pregnancies after the first insemination, total number of born piglets and number of liveborn piglets converted per one litter in treated primiparae and secundiparae did not differ significantly (P greater than 0.05) from the control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102581 TI - [Occurrence of PSE and DFD meat in swine slaughtered under emergency conditions]. AB - The occurrence of qualitative changes in meat was studied in a set of 1008 pigs slaughtered in four sanitation slaughter houses for the period of 12 months. PSE meat was found in 206 pigs (20.43 per cent) and DFD meat only in 9 pigs (0.89 percent) of the total number of pigs examined. The rule was applied that the defect should be demonstrated by two of three commonly used parameters (the pH value, colour and water loss by dripping). The highest occurrence of qualitative changes in meat of PSE type was registered in the group of animals with a defect of the respiratory organs (32.53 per cent) and the lowest in animals with diseases of sexual organs, including parturition complications (5.00 per cent). A similar trend was recorder even in the DFD meat occurrence. As to the seasons, the highest percentage of occurrence of PSE defects was in July and August (35.41 and 29.06 per cent) and the lowest (8.64 and 10.97 per cent) in March and January. The actual disease is proved to be only one of the secondary stress to induce the PSE meat formation. PMID- 2102582 TI - [The effect of the sperm count in the insemination dose and storage time on the fertilizing capability of the ejaculate of roosters]. AB - Ejaculate of cooks was diluted by the Wishart and Davtjan diluents at a ratio of 1 : 1 and stored at a temperature of 4 degrees C during 2, 24, 48 and 72 hours before insemination of laying hens by the doses of 25, 50, 75, 100 and 150. 10(6) spermatozoa. With both diluents, egg fertility higher than 90 per cent was gained after 48 hours of keeping the ejaculate in sperm doses of 75 and 100 . 10(6) spermatozoa in the case of both diluents. PMID- 2102583 TI - [Acid-base equilibrium values in the blood of dogs during training and work stress]. AB - Separate components of acid-base balance in blood (ABR)-pH, pCO2, BE, SB, BB-were studied during the long-term drill of service dogs of two age categories. These service dogs were included in two different work strain groups (patrol dogs and searching dogs). The results of long-term drill demonstrated, in particular, significant changes in dynamics of pH and pCO2. The pH values were permanently raised as compared with reduced pCO2 values during the whole period of 130-days exercise and as compared with the initial values. Other components of acid-base balance in blood do not show such variations (patrol and searching dogs) and these components justify that the adaptation of organism to the given strain gained suitable stabilisation. For studying the psychical and physical strain in service dogs it is recommended to include pH and pCO2 in the tests. PMID- 2102584 TI - [Suppressive effects of ionizing radiation on immunoproductive cells in laboratory mice]. AB - The very sensitive Jerne method of detecting the plaque-forming cells was used in the study of the immunosuppressive effect of ionizing radiation on laboratory mice. A significant immunosuppression was obtained after irradiation of the individual groups of mice with 3, 4, 5 and 6 Gy. Successive regeneration of the immunity system occurred after 42 hours only in the groups of mice irradiated with 3 and 4 Gy. mice; ionizing radiation; immunoproductive cells; Jerne method. PMID- 2102585 TI - [The Sertoli cell nucleolus in domestic and wild animals]. AB - Sertoli cells produce special microenvironment for developing germ cells; therefore it is assumed that they play primary role in the onset and control of spermatogenesis. In this connection we extended our previous study on the ultrastructure of Sertoli cells in different domestic and wild animals with special regard to nucleolus. Sertoli cells of domestic and wild ruminants possess the typical vesicular nucleolus except for fallow deer, in this species no vesicular nucleolus occurs in Sertoli cells even during the rut. In roe.buck, another wild ruminant with seasonal spermatogenesis, cyclic changes were found in the nucleolus of Sertoli cells. If no spermatogenesis is present, the Sertoli cells have a reticular nucleolus. Membranous vesicles appear in the nucleolus of Sertoli cells of roe-buck at the onset of spermatogenesis 1-2 months before rut. In domestic ruminants with continuous spermatogenesis the vesicular nucleolus in Sertoli cells is present permanently. During postnatal development of bull and ram the vesicular nucleolus appears in Sertoli cells just before the onset of spermatogenesis. In experimental cryptorchidism of bulls a vesicular nucleolus is found in the Sertoli cells. Our observations and experiments support a hypothesis that Sertoli cells have primary role at the onset and the maintenance of spermatogenesis. PMID- 2102586 TI - A stochastic model of the genetic predisposition to ageing: an application to twin data. AB - In previous papers a stochastic model of the ageing process has been proposed. Some genetic parameters (redundance, repair) have been used to explain the observed differential predisposition to the process and family heredity. Because the process is basically due to effective random mutations, any individual of the population would be predisposed differently to ageing according to the structure of his/her genome. In the present paper, the previous model is generalized to take into account an additional genetic parameter, namely, the stability against random mutations, defined as the probability that a random mutation in a codon would produce no mutation in the corresponding protein. Estimation problems connected with the model are approached on the basis of twin data in maximum likelihood estimation as well as in bayesian framework. Some comparisons between the two methods are reported. PMID- 2102587 TI - Population-based twin registries: illustrative applications in genetic epidemiology and behavioral genetics from the Finnish Twin Cohort Study. AB - The population-based twin registries of Denmark, Finland, Norway and Sweden represent an extraordinary resource for scientific research. Although each register has its own history and composition, they share certain common qualities. All the Nordic countries have a long tradition of population registration, a high standard of living and health-related registers of high quality. The large size of the registers means that they are uniquely placed for representative studies of rare occurrences. Examples of studies that these registers make possible are illustrated with data from the Finnish Twin Cohort, which in its first phase consisted of over 17,000 like-sexed twin pairs born before 1958. It has been recently expanded to include multiple births between 1958 and 1986 (nearly 23,000 sets) and their first-degree relatives. During this period the DZ/MZ ratio decreased, while an increase in MZ twinning rates was observed between 1974 and 1986. PMID- 2102588 TI - Selection bias in disease-related twin studies. Data on 11,154 adult Finnish twin pairs from a nationwide panel. AB - The effect of migration on pairwise concordance for disease was assessed in 11,154 twin pairs of the Finnish Twin Cohort Study by comparing the pairs living in the same province to the pairs which members were living in different provinces of Finland. The cumulative incidence of psychosis and hypertension for the years 1972-1985 were analyzed. The cumulative concordance of psychosis for those MZ twin pairs living in the same province were higher than for those MZ pairs living further apart. Similar findings were found among DZ pairs for psychosis. The cumulative concordance of hypertension was only slightly higher among those MZ and DZ pairs living in the same province compared with pairs living in different provinces. These results indicate an overestimation of concordance of psychosis caused by selective migration. This bias in twin studies is likely to influence heritability estimates in a sample of limited geographical area. PMID- 2102589 TI - Persist or quit? Testing for a genetic contribution to smoking persistence. AB - We consider three alternative parametric models to describe genetic and environmental influences on smoking initiation and smoking persistence. Under the single liability dimension model, the same genetic and environmental influences which determine smoking initiation also influence smoking persistence. Under the independent liability dimensions model, independent initiation and persistence dimensions determine onset of smoking, and persistence in those who become smokers. The combined model also postulates separate initiation and persistence dimensions, but allows for the possibility that some smokers are so low on liability to smoke on the initiation dimension that they become ex-smokers for this reason. Reanalysis of London twin data published by Eaves and Eysenck support the single liability dimension model. We discuss the difficulty of reconciling this finding with the hypothesis that nicotine dependence is a major determinant of smoking persistence, but caution that sample sizes in the London twin study were small. PMID- 2102590 TI - Definitive methods of zygosity determination in twins: relevance to problems in the biology of twinning. AB - Many studies of embryogenesis and fate of twin pregnancies are invalidated because zygosity is not determined definitively, or is assumed on the basis of inadequate criteria. This paper briefly reviews methods of zygosity determination. It reports published results and a new series of twins in which zygosity was determined by DNA fingerprinting. Implications for methods of prenatal diagnosis of zygosity are discussed in the context of the occasional need for intervention in twin transfusion syndrome or in twins discordant for major malformations. Definitive zygosity and placental anatomy (number of chorions and amnions) is discussed as the firm substrate for studies of normal and abnormal twin development. PMID- 2102592 TI - Genetic variance and heritability of temperament among Chinese twin infants. AB - In order to examine the genetic variance and heritability of temperament among Chinese infants in Taiwan, a total of 62 pairs of same-sexed twin infants given birth in four major general teaching hospitals in Taipei City were studied. Based on placentation and 12 red blood cell antigens, 44 MZ and 18 DZ pairs were identified. Temperament was assessed at the age of six months by the Chinese edition of Carey's Temperament scale. Significant genetic variance was observed for activity level, approach or withdrawal, intensity of reaction, quality of mood, and threshold of responsiveness, with a heritability of 0.64, 0.56, 0.74, 0.39, and 0.45, respectively. There was no significant intrapair difference in temperamental characteristics between monochorionic and dichorionic MZ twins. PMID- 2102591 TI - Chronological changes in genetic variance and heritability of anthropometric characteristics among Chinese twin infants. AB - In order to examine the chronologic changes in genetic variance and heritability of anthropometric characteristics of Chinese infants in Taiwan, a total of 521 pairs of same-sexed twin neonates given birth in four major general teaching hospitals in Taipei City were studied. Based on the placental pattern and 12 red blood cell antigens, 428 MZ and 93 DZ twin pairs were identified and followed up to the age of one year. There was no significant genetic variance for all anthropometric characteristics adjusted for sex and gestational week before the age of six months. After adjusting for sex and gestational week, a significant genetic variance was observed at the age of six months, with heritability values of 0.51 (weight), 0.63 (head circumference), 0.77 (chest circumference), and 0.53 (arm circumference), as well as at one year, although with considerably lower heritability values. This implies that growth is dynamically determined by both genetic and environmental factors during infancy. PMID- 2102593 TI - Higher order multiple births: natural wonder or failure of therapy? AB - Data of 601 families with triplets and higher multiples have been collected. Since about nine years the number of higher-order births has been increasing enormously. The average pregnancy duration and the average birthweight of these mostly premature children have been declining from year to year. Despite the progress in neonatology, the death rate and the rate of handicapped children is very high. To prevent such disastrous outcomes, treatments for infertility should be performed only by physicians in centers with strong controls. Selective abortions are no regular solution to the problem of higher multiple gestation. PMID- 2102594 TI - An examination of the psychological and behavioural factors in the development of language retardation in twins. AB - Using therapeutic intervention, the psychological and behavioural factors in the development of language retardation in two pairs of 4-year-old MZ twins have been examined. Although some factors are common to those found in singletons with language retardation, the factors peculiar to the twin situation are highlighted. PMID- 2102595 TI - Raising twin babies and problems in the family. AB - Out of 296 mothers of twins interviewed about difficulties encountered while rearing twins, 49% mentioned inadequate sleep, 18% financial strain, 39% emotional disturbance, 22% disturbance in the marital relationship, and 43% lack of time to take care of other children. With the growth of twins, the problems gradually decreased, except for emotional disturbance, the most difficult period being the first year. Only 15% reported leaving the babies in the care of relatives during the day time. Overall, 68.2% felt the support from the father, but 39% of them felt the support was useless; 49% felt support from the mother-in law, but 43% of them regarded the mother-in-law to be of no help; 36% were supported by their own mothers, but 54% mentioned that they had received little help. One must conclude that social support from relatives was inadequate. Public policy should take this fact into account and provide public health nurses and social workers to help the mothers of twins, especially during the first year. PMID- 2102596 TI - An agenda for meeting the special needs of multiple birth families. AB - Over 80,000 multiple birth babies are born each year in the U.S. Their families must cope with a constellation of complex physical and psychosocial challenges, which jeopardizes their health and functioning. The demands of twin pregnancy and the parenting of twins, triplets, quadruplets, quintuplets or more puts these families at disproportionately high risk for infant mortality, birth defects, child abuse, substance abuse, financial problems and marital problems. Health and social service resources must be developed to alleviate the stresses associated with multiple birth and to empower parents to cope well. Guidelines for policies, parent education, professional training and service delivery developed for the California Department of Health Service, Maternal and Child Health Branch, are here offered for the consideration of policy makers and public health planners. PMID- 2102597 TI - In memoriam Professor Ferencz Kiss (1889-1989). PMID- 2102598 TI - "Specificity versus (quasi-) randomness" revisited. AB - Speculation on neuron connectivity in the cerebral cortex, made some ten years ago, were re-evaluated in the light of modern cross identification methods. The identification of individual neurons and their synapses, including physiological characterization, detailed light microscope analysis of the same neurons, and immunocytochemical analysis of these neurones on the light microscope level and of their synapses on the level of the electron microscope, indicate that the specificity of local neuronal connections was underestimated in the earlier studies. Although the new methods revealed a higher degree of specificity in the choice of their connections, there seems to remain ample room for epigenetic (or functionally induced) plasticity of re-arrangement in neuronal circuits during later - even in postnatal - stages of development. PMID- 2102599 TI - Morphological alterations of neurons in brains of kittens prenatally exposed to ethanol. AB - The brains of kittens prenatally exposed to ethanol were studied by the rapid Golgi method at PN1 and PN9 days. The sizes of the alcohol damaged brains were different. Delayed gyrification was observed on the brain surface. The neurons in subcortical (thalamic) centres and cortical areas developed later than in normal animals. Between days PN1 and PN9 rapid changes occurred in the development of the structural elements of brains of prenatally alcohol exposed kittens. PMID- 2102600 TI - Applied anatomy of the cochlea for the purpose of the cochlear implant technique. PMID- 2102601 TI - The epidural ligaments during fetal development. AB - The topography of the developing epidural ligaments in man was investigated by dissecting 12 fetuses ranging from 60-310 mm in CR length. It was found that in a 60 mm CR length fetus, the epidural space is occupied by an ubiquitous connective tissue which in longer fetuses becomes reduced into topographical structures. Posterior, lateral and anterior ligaments could be identified. The atlantodural and the sacral ligaments appear to be permanent ligaments anchoring the dural sac, whereas most of the dorsal ligaments become resorbed during the development of the fetus. These ligaments may be responsible for the compression of the nerve root that occurs when the dural sleeve and the contained nerve root are stretched over a protrusion (e.g. a protruded disc). PMID- 2102602 TI - Types of neurons and synaptic relations in the lateral superior olive of the cat: normal structure and experimental observations. AB - Light and electron microscope studies on normal and experimental material in the lateral superior olive (LSO) of cat revealed the presence of three types of neurons: (i) fusiform cells characterized by the large number of terminals articulating with them and projecting to the nuclei of the lateral lemniscus (NLL) and central nucleus of the inferior colliculus (CNIC) (ii) marginal cells embedded in the neuropil of the fibrous capsule and sharing input and output characteristics with the fusiform neurons (iii) multipolar cells with spinous dendrites, local axonal spread and synaptic relation restricted to few afferents only. Four distinct types of axon terminals were distinguished on the basis of their size, vesicle content, membrane attachments, postsynaptic relations and origin. (i) Large terminals with asymmetrical membrane contacts and round vesicles (AR) were of ipsilateral cochlear nucleus origin and articulated predominantly with fusiform and marginal projection cells. (ii) The majority of small AR type terminals arose from the spherical cells of the ipsilateral nucleus of the trapezoid body (NTB). Their number was larger on the fusiform and marginal cells. (iii) Medium sized terminals of symmetrical membrane apposition and pleomorphic vesicles originated from the ipsilateral NLL and CNIC. Their quantitative distribution indicated preference for the multipolar cells. (iv) Profiles with symmetrical membrane contacts and flattened vesicles (SF) type were considered to be terminals of the spinous multipolar interneurons, thus local in origin. PMID- 2102603 TI - A rare case of pancreatic cyst. AB - A post-traumatic pancreas cyst is described in a 16-year-old young man causing symptoms only 13 years after the accident. The formation of the cyst happened on an ischaemic basis. In classical terms this cyst is a transitional form between real cysts and pseudocysts of the pancreas. PMID- 2102604 TI - The significance of gastric lymph-vessels in the surgical treatment of cancer of the stomach. AB - Authors give an account of the classification of gastric lymph-circulation and lymph nodes suggested by the Japanese Research Society for Gastric Cancer. The importance of lymphatic structures in the accurate determination of oncological stages of gastric cancer and that of a radical lymphadenectomy during resection is emphasized. Total or subtotal removal of the stomach should be completed with the removal of primary, secondary and tertiary lymph node groups. In cases of stages II-IV, the 5-year survival rate is increased by 30-50% without an increase of postoperative lethality and complications. The operation time is prolonged by 40-60 min if resection is combined with a lymphadenectomy. PMID- 2102605 TI - Differential diagnostic problems in desmoid and fibrosarcoma. AB - On the basis of 10 patients treated at the Orthopaedic Clinic of the Semmelweis University Medical School, the histology, clinical symptoms, recurrence rate and principles of surgical treatment of the disease are discussed. Two further cases are described in detail in which initially a desmoid was diagnosed but later based on the clinica-history and the histological appearance of recurrences the diagnosis of a differentiated fibrosarcoma had to be established. An account of differential diagnostic criteria between desmoid and fibrosarcoma is given. PMID- 2102606 TI - The effect of xylene exposure on the liver. AB - The author, with the xylene exposure of mice, rats and rabbits (sc, ip, per os, inhalation), as well as with xylene inhalation following the partial hepatectomy of rats, or the ligation of their common bile duct, wanted to find out whether xylene did have a selective or elective hepatotoxic effect. Using morphological (routine histological, enzyme-histochemical, electron microscopical, morphometrical), biochemical, clinical and analytical-chemical methods, it was found, that the xylene increased the activity of the hepatic biotransformation system, its adaptation to the xylene exposure; the xylene had neither selective, nor elective hepatotoxic effect in the examined species. The effect of xylene increasing the biotransformation ability of the liver is not inhibited by partial hepatectomy and ligation of the common bile duct; the so-called enzyme induction, which evolves at the effect of xylene, hinders the mitotic activity following the partial hepatectomy (defensive ability against xenobiotics takes priority over regeneration). PMID- 2102607 TI - A pathogenesis-oriented classification of congenital abnormalities. AB - The modern anatomical-pathological approach in the evaluation of congenital abnormalities (isolate: single, complex, polytopic field defect, sequence and multiple: syndrome, association, random combination) is shown. Due to the population-based Hungarian Congenital Malformation Registry a number of new congenital abnormality entities were described. PMID- 2102608 TI - Factor VII and dietary fat intake. PMID- 2102609 TI - Characterization of snake venom principles affecting blood coagulation and platelet aggregation. PMID- 2102610 TI - Thrombin-like venom enzymes: structure and function. PMID- 2102611 TI - Thrombin inhibition by synthetic hirudin peptides. PMID- 2102612 TI - Molecular genetics of alpha 2 plasmin inhibitor. AB - Analysis of the cDNA for alpha 2PI and its expression experiment indicated that the leader sequence is pre-pro peptide containing an N-terminal hydrophobic prepeptide (signal sequence) of 27 amino acids, followed by a hydrophilic propeptide of 12 amino acids. The alpha 2PI gene contains 10 exons and 9 introns distributed over approximately 16 kilobases of DNA. Two families of hereditary alpha 2PI deficiency were found to have changes of nucleotide sequence in an exon coding for plasma alpha 2PI, resulting in productions of variant proteins. These proteins are mostly retained within the cells, resulting in a deficiency of alpha 2PI in a circulating blood plasma. PMID- 2102613 TI - The mechanisms of the activation of plasminogen by streptokinase and urokinase. PMID- 2102614 TI - Protein C and fibrinolysis: a link between coagulation and fibrinolysis. AB - The effect of purified human activated protein C (APC) on fibrinolysis was studied by using in vitro clot lysis techniques. Clots were formed from citrated blood or plasma (supplemented with 125I-labeled fibrinogen) by adding thrombin and Ca(2+)-ions; lysis of the clots was achieved by the addition of tissue-type plasminogen activator before clot formation. The gradual release of labeled fibrin degradation products from the clot into the supernatant was taken as a measure for the lysis rate. It was demonstrated that the acceleration of clot lysis by APC added before clot formation depends on the presence of Protein S, Ca(2+)-ions and phospholipids. These observations suggest a role of APC as anticoagulant in clot lysis, since the cofactors for the expression of its anticoagulant and profibrinolytic effect are very similar. Indeed, we could demonstrate that the profibrinolytic effect of APC in vitro is associated with reduction of thrombin generation through the coagulation cascade by inactivation of factor VIIIa and factor Va. For instance, APC did not accelerate the lysis of factor X deficient blood clots. More generally, thrombin generation was associated with retarded fibrinolysis in vitro. Consequently anticoagulants such as APC or Heparin are profibrinolytic, whereas pro-coagulants such as phospholipids (in cell-free plasma) inhibit fibrinolysis through the generation of thrombin. Thrombin thus plays a crucial role as a link between coagulation and fibrinolysis. As thrombin is able to inhibit the lysis of blood and plasma clots, and not of purified fibrin clots, we hypothesize that thrombin inhibits lysis through an as yet unidentified mediator in plasma. PMID- 2102615 TI - Transformation of prostacyclin (PGI2) to a biologically active metabolite: 5(6) oxido-PGI1 by cytochrome P450-dependent epoxygenase. AB - The renal epoxygenase has been demonstrated to be an active pathway for the conversion of PGI2 to a new, previously unreported, metabolite. This metabolite was isolated and identified by radiogas-chromatography-mass spectrometry as 5 hydroxy-6-keto PGF1 alpha. Its structure was further confirmed by comparison of the mass-spectra to that of the synthetic standard. The formation of 5-hydroxy-6 keto PGF1 alpha in the kidney suggested epoxidation of prostacyclin via the renal epoxygenase as an alternative pathway of PGI2 metabolism. PMID- 2102616 TI - The structure and evolution of vertebrate fibrinogen: a comparison of the lamprey and mammalian proteins. AB - The blood plasmas of all vertebrate animals contain a six-chained fibrinogen molecule that is polymerized into fibrin upon the thrombin-catalyzed removal of fibrinopeptides. In all cases, also, the polymerization reaction is inhibited by Gly-Pro-Arg-ending peptides. The complete amino acid sequences of human, rat and lamprey fibrinogens are known, permitting an assessment of just which sequence features are essential for polymerization. To an extent, the same approach can also be applied to the associated phenomena of fibrin cross-linking by factor XIII, plasminogen and plasminogen activator binding, and vessel wall-fibrinogen interactions. PMID- 2102617 TI - Studies on the localization of fibrinogen binding sites on platelet glycoprotein IIIa. PMID- 2102618 TI - Platelet-fibrin interaction in the suspension and under flow conditions. AB - Interactions between platelets and fibrin are important in hemostasis but often confused with platelet-fibrinogen interactions. A stirred mixture of solubilized fibrin and washed platelets at neutral pH range showed drastic reduction in turbidity and concomitant platelet adhesion onto newly formed fibrin strands. This platelet-fibrin interaction did not require platelet activation nor did it cause platelet aggregation. A device consisting of a parallel-plate flow chamber mounted on a fluorescence microscope has been constructed to allow direct visualization and recording of platelet-fibrin interaction under flow conditions. Platelets in whole blood adhered to the fibrin-coated portion but not to the uncoated portion of the flow chamber. Slow motion playback of video tapes indicated that the adhesion phenomenon was a dynamic process that involved attaching, detaching, relocation and transient contact. The fibrin coating influenced platelet adhesion both by increasing the number of cells making short term attachments to the surface and by increasing the duration of cells attached to the surface. These observations provided basic characteristics of platelet fibrin interaction. PMID- 2102619 TI - An independent haemostatic mechanism: shear induced platelet aggregation. AB - We have published (1) evidence indicating that high shearing forces alone applied to platelets expose and activate a unique domain on glycoprotein IIb/IIIa (GPIIb/IIIa) at the platelet surface. In the presence of von Willebrand's factor (vWf) and divalent cations the platelets will aggregate. This paper reviews the extensive literature on high shear effects. It describes a device in which high shear produced by forcing heparinised whole blood through a complex filter normally results in platelet activation; the platelets aggregate and then block the filter. This system is inhibited by antibodies to GPIIb/IIIa and to vWf: fibrinogen is apparently not involved. The same antibodies to GPIIb/IIIa and vWf prevent high shear induced thrombosis occurring in vivo in animal models. The filter blockage is not influenced by aspirin, heparin and ticlopidine and so involves a different mechanism from the aspirin sensitive mechanisms involved in clinical thrombosis prevention in vivo in man. While there are a number of unexplained phenomena in this global test nevertheless this filter model is a simple way of studying a recently recognised pathway which is almost certainly involved in thrombogenesis in man. PMID- 2102620 TI - Fibrin and the vessel wall. AB - Fibrin is a major component of atherosclerotic plaques, and there may also be situations in which intravascular fibrin is formed in contact with the endothelium. The studies to be presented describe the distribution of fibrinogen/fibrin I, fibrin II, and fragments D and D-dimer in normal vessels and atherosclerotic plaques of increasing severity and also describe some functional effects of fibrin on normal endothelium. Immunohistochemical studies using three specific monoclonal antibodies with the avidin-biotin complex immunoperoxidase technique demonstrated that little fibrinogen/fibrin I or fibrin II and no D/D dimer were detected in normal aortas. In early lesions and in fibrous plaques, fibrinogen/fibrin I and fibrin II were distributed in long threads and around vessel wall cells. D/D-dimer was not seen in early lesions. In advanced plaques all three molecular forms were detected in areas of loose connective tissue, in thrombi, and around cholesterol crystals. Thus increased fibrin formation and degradation may be associated with progression of atherosclerotic disease. Additionally, the presence of fibrin II around vessel wall cells suggests that these cells may be involved in the fbgn to fibrin transition within the vessel wall. The second aspect of the work to be presented concerns effects of fibrin on vascular endothelium. Fibrin formed on the surface of cultured human umbilical vein endothelial cells stimulated production of prostacyclin and tissue plasminogen activator by the cells in a time- and dose-dependent manner. Stimulation of prostacyclin was completely inhibited by indomethacin and partially inhibited by actinomycin D, cycloheximide, and trifluoperazine, while stimulation of t-PA synthesis was completely inhibited by actinomycin D and cycloheximide and partially inhibited by cytochalasin D, vinblastine, and trifluoperazine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102621 TI - Coronary thrombosis: pathogenesis and prevention. AB - Acute myocardial infarction is most commonly initiated by fissuring of an atheromatous plaque. Through such fissures the blood is exposed to thrombogenic constituents of the intima, causing thrombotic obstruction of the coronary artery. Why plaque fissuring occurs is not known. Our investigation is to establish which types of plaque undergo fissuring by relating their mechanical with their cellular and biochemical properties; and to quantify the distribution of fissures. Results so far indicate that fissures occur predominantly in plaques with lipid pools in one segment of intima, and that the commonest single site of fissuring is that of maximal stress concentration as predicted by computer modelling. The results also suggest that arterial spasm at the immediate site of fissuring is not involved, as more than half the fissures occur at sites where there is no residual medial smooth muscle. Obstructive coronary thrombosis is initiated in most cases by plaque fissure with local haemorrhage which induces intravascular platelet aggregation. Recent observations with novel techniques have provided evidence that platelet aggregation in vivo is initiated by ADP and potentiated by thromboxane A2 and thrombin, with actual contribution of exposed collagen still undetermined. These observations provide an explanation for the limited effectiveness of any simple platelet-inhibiting drug, including Aspirin, by itself whenever arterial, eg. coronary or cerebral thrombosis is initiated by haemorrhages into atheromatous plaques. On the other hand, Aspirin is significantly effective when myocardial infarction follows unstable angina and when strokes follow transient episodes of cerebral ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102622 TI - Thrombotic microangiopathy. PMID- 2102623 TI - Nucleotide sequences of the three genes coding for human fibrinogen. PMID- 2102624 TI - The pharmacology and clinical pharmacology of defibrotide: a new profibrinolytic, antithrombotic and anti-platelet substance. AB - Defibrotide, a deoxypolyribonuclide, has been found to modulate endothelial cell function causing increase in t-PA and decrease in PAI levels and also increase in PGI2 production. In addition, it increases platelet c-AMP levels and decreases MDA and TXB2 formation in human. Defibrotide inhibits platelet aggregate formation in vitro experiments as well as end-to-end anostomosis in rats. So, defibrotide inhibits the activation of platelets. Besides an increase of protein C and S levels a synergic action of heparin was observed in animal experiments. A strong antithrombotic effect has been observed in animal models. The drug has a beneficial effect in the cases of DVT, POVD, stroke and thromboembolism. Through its action we may say that the drug acts in a novel fashion in contrast to the other drugs used in this area. Defibrotide is a single-stranded polydeoxyribonucleotide obtained from deoxyribonucleic acid of mammalian lungs by controlled depolimerization. Since 1981 in our laboratory and in the clinical department we have been investigating a newly developed agent defibrotide in vitro experiments, animal experiments, and also its clinical pharmacology and clinical application. Some of our findings are already published and compared with literature (40, 43, 46). Because of the limited space we are not going to review the literature in detail but we are going to summarize our observations on this compound in the following order. I--in vitro experiments, II--Animal experiments, III--clinical pharmacology in human. PMID- 2102625 TI - On the identity of fibrin(ogen) oligomers appearing during fibrin polymerization. PMID- 2102626 TI - Abnormal fibrinogens with two structural defects. PMID- 2102627 TI - Electrophoretic characterizations of cross-linked fibrinogen derivatives in blood and vascular tissue by zonal immobilization on glyoxyl agarose. AB - Direct immunoprobing of electrophoregrams of plasma and intimal protein on glyoxyl agarose and composite-gels with polyacrylamide have uncovered novel modes of cross-linking of fibrinogen that differ from those previously characterized. These modes of cross-linking involve the A alpha-chains of fibrinogen and hybrid cross-linking of alpha- and gamma-chains. PMID- 2102629 TI - The initiation of the tissue factor dependent pathway of blood coagulation. PMID- 2102628 TI - Prothrombinase: recognition and developments. PMID- 2102630 TI - [Tuberculosis yesterday, today and tomorrow (2)]. PMID- 2102631 TI - [Biodynamic hierarchy of the intrinsic articular unity]. PMID- 2102632 TI - [Surgery for esophageal adenocarcinoma associated with gastroesophageal reflux]. PMID- 2102633 TI - [Leisure and health]. PMID- 2102634 TI - Lasers in surgery. PMID- 2102635 TI - Laser therapy. PMID- 2102636 TI - Computer-guided laser for neurosurgery. AB - On the basis of over 40 neurosurgical laser operations, including CO2, Nd-YAG and simultaneous CO2/Nd-YAG laser procedures, a computer-guided system for spatial control of the laser beam has been developed. The pilot laser has several modes: it can direct the neurosurgeon along the central axis of the surgical microscope to stereotactically determined point-like targets or outline selected layers of underlying volume targets onto superficial surfaces such as scalp and cortex and onto the tissue at the appropriate depth. The active treatment laser can be guided by preoperative CT/MRI or intraoperative ultrasound image data for layer by-layer resection of tumor. The laser system can be connected to the surgical field by rigid stereotactic means or by neuronavigator. In the present system, a special brain surgery adapter coordinates the imaging system and laser to the surgical field. Thus, the laser system can be used for image-guided surgical orientation, for demarcation of lesions and for actual layer-by-layer removal of tumor. PMID- 2102637 TI - Possibilities of laser in the treatment of urinary bladder cancer. AB - Clinical use of laser in the treatment of urinary bladder tumours has been practiced since 1976. Today, the method is widely accepted as a simple and effective method for destroying superficial bladder tumours. In selected cases of muscle invasive tumours of stage T-2 beneficial long term results are reported. Locally advanced tumours of stage T-3 or T-4 are beyond the possibility of cure by the laser. PMID- 2102638 TI - Neodymium-YAG laser in the treatment of localized prostate cancer. AB - The combination of transurethral resection and subsequent Neodymium-YAG laser irradiation has been practiced for radical treatment of localized prostate cancer since 1981. One hundred and eighteen patients have been treated and the observation time ranges 6-98 months. The treatment is performed endoscopically in two separate steps. The procedure is simple and complications are few. One hundred and four patients are evaluated as disease-free survivors. The overall actuarial disease-free survival rate is 88% in the 4-8 year period. The results compare satisfactorily with results obtained by other methods. Recently published results from other clinics confirm the laser to be promising in the treatment of localized prostate cancer. PMID- 2102639 TI - The role of lasers in otolaryngology. PMID- 2102640 TI - Squamous cervical intraepithelial neoplasia: the role of laser treatment. AB - A review of the CO2 laser in the current management protocol for squamous cervical intraepithelial neoplasia (CIN) is presented. The laser provides the clinician with a versatile instrument that enables accurate application of biophysical insults to the full range of CIN lesions likely to be encountered. Side effects and cure rates compare favourably with the alternative methods of local destruction presently available. The final benchmark of success of all such treatments will remain the prevention of subsequent invasive cancer as observed on long-term follow-up. It should be noted that for some of the methods discussed such information is not yet available. PMID- 2102641 TI - Endoscopic application of laser in gynecology. PMID- 2102642 TI - Photodynamic therapy. AB - Photodynamic therapy (PDT) is a new modality of cancer treatment. It is based on the use of photosensitizing agents and laser light which interact and produce singlet oxygen. This toxic compound destroys malignant tumours while healthy tissue remains intact. The present paper reviews the method of PDT and its possible clinical applications. PMID- 2102643 TI - Interstitial laser hyperthermia in tumour therapy. AB - The clinical applications of non-laser thermal techniques are limited by technical and practical problems. Experimentally, Interstitial Laser Hyperthermia (ILH) is a feasible technique for producing precise, well defined and predictable areas of tissue necrosis which heal safely in normal liver and pancreas. Early clinical experience has shown that ILH is simple to perform and produces well defined areas of thermally mediated necrosis in liver, breast and pancreatic tumours with negligible morbidity and mortality. Further research is necessary to refine the efficacy of what is a promising new treatment modality. PMID- 2102644 TI - [Lysozyme in calves]. AB - Relatively high lysozyme concentrations, depending on age, were recorded from intestinal content, spleen, liver, kidney, lung, lymph nodes, and mucosa of calves. Yet, only minor quantities of lysozyme were found in blood serum or plasma and in granulocytes. Physicochemical characterisation, precipitation, using polyclonal antisera, and crosswise neutralisation of lysis reaction were likely to suggest occurrence of immunological relationship reactions as well as differences between organ lysozymes, on the one hand, and intestinal lysozymes, on the other. PMID- 2102645 TI - [PMSG dosage precision in young and old sows in the course of biotechnical ovulation synchronization. 3. Fertility and litter effects]. AB - One single PMSG batch, Pregmagon-Dessau, was compared with other PMSG doses on 2,126 adult sows and 1,700 gilts from five farms. Additional comparisons were made with other Pregmagon or Prolosan batches on 1,178 adult sows and 1,026 gilts. All experiments were made in the context of a programme for ovulation synchronisation and term-oriented insemination. Doses of 700, 800, 900, and 1,000 IU were tested on adult sows and 600, 800, and 1,00 on gilts, with the mean dose of 800IU being found to be sufficient or superior to other doses for fertility results. Doses for adult sows could be adjusted and related to present and previous litter numbers, with the dosage being between 700IU (treatment for third litter) and 700 to 800IU (treatment following average to high previous litter. The preferential dose for gilts was found to be 800IU. Higher PMSG doses (up to 1,000IU) should not be used in synchronisation of ovulation and term-oriented insemination unless extraordinary conditions were safely established. PMID- 2102646 TI - [Several methods for determining total titers of free alpha-amino acids in body fluids]. AB - Comparisons were made among different variants of ninhydrin reaction to determine overall titres of free alpha amino acids in body fluids. Included were para benzoquinone, 2,4,6-trinitrobenzene sulphonic acid, and 2,4-dinitro-1 fluorobenzene (DNFB). The best reproducibility of results was recorded from DNFB which can be used, as well, for analysis of milk or rumen juice. PMID- 2102647 TI - [Subacute butyric acid exposure in cattle. 4. Clinical influence and effect on the carbohydrate-fat metabolism and liver function of cows]. AB - Eleven cows in late lactation were exposed to butyric acid for three weeks and were compared to five controls. Two intraruminal doses were daily applied, that is 1.0 g/kg B.W. of butyric acid to six animals and 1.0 g/kg B.W. of sodium butyrate to another five. Decline in milk yield was clinically recorded in response to butyric acid, while muscle tremor and diarrhoea resulted additionally from sodium butyrate. Behaviours of the clinico-chemical parameters of beta-OH butyrate, glucose, free fatty acids, bilirubin, ASAT, gamma-GT, AP, and cholesterol were comparable to those in fattening bulls. Liver damage was not safely established. Some of the clinico-chemical alterations were more strongly pronounced after administration of sodium butyrate. One cow fell ill with ketosis under butyric acid load. PMID- 2102648 TI - [Subacute butyric acid exposure in cattle. 5. Effect on the acid-base equilibrium and protein metabolism in cows]. AB - Acid-base balanced in cows were but slightly affected by butyric acid exposure experiment over three weeks. Applications of sodium butyrate over the same period of time, on the other hand, was associated with buildup of alkalosis in the second half of the experimental period, with alternation of loading, compensation, and reloading being recordable. Nitrogen metabolism in cows was but slightly affected under the given experimental conditions. However, clearly noticeable impairment of nitrogen metabolism was exhibited by one cow that had fallen ill, in the course of experimentation. PMID- 2102649 TI - [Subacute butyric acid exposure in cattle. 6. Effects of a butyric acid or a sodium butyrate exposure up to 2.0 g. per kg. body weight per day]. AB - Two cows each received intraruminal applications of 1.0 g/kg B.W. of butyric acid or sodium butyrate, for three weeks running, before daily applications were increased up to 2.0 kg/B.W., within one week. Resulting alterations primarily included increase in acidosis or alkalosis, whereas the typical symptoms of ketosis were lacking. Signs of impaired liver function were to some extent recordable in response to sodium butyrate. PMID- 2102650 TI - Recombinant virus vaccines--present status and future prospects. AB - Several DNA viruses have recently emerged as useful eucaryotic vectors. The ability to incorporate large amounts of foreign DNA in the vaccinia virus genome without loss of infectivity, evidence to correct glycosylation and processing of expressed proteins and the wide host range of vaccinia virus all contribute to the versatility of this system as a research tool. The development of recombinant DNA technology and its use in genetic engineering has provided opportunities to construct DNA-recombinant viruses that can provide protection against a spectrum of diseases. A brief account is given of current developments and future prospects of DNA recombinant viruses, with particular reference to vaccinia virus. PMID- 2102651 TI - Molecular cloning of porcine parvovirus DNA for the purpose of obtaining viral antigen synthesis in bacteria. AB - An expression of porcine parvovirus 1.05 kb DNA fragment was obtained in Escherichia coli under the control both of Pr-lambda and lac-promoters. The product of expression under Pr-control was demonstrated to show PPV-specific antigenic properties. Its electrophoretic mobility corresponded to a molecular weight of approximately 45 KD. PMID- 2102652 TI - Characterization of RD114-related endogenous cat retroviral elements ECE2. AB - RD114 virus is an endogenous xenotropic Type C retrovirus of domestic cat. Previously, it had been shown that genomic DNA of cat contained approximately 20 copies of RD114-related sequences. Only one encoded for the replication-competent RD114 virus. The endogenous sequences exhibited substantial sequence conservation within the gag and pol genes and LTRs, but were characterized by deletions and substitutions within the env region. The endogenous cat retroviral element ECE2 was isolated by screening a genomic DNA library of cat liver DNA with an env specific cDNA of RD114 virus. It contained an env region which differed from all RD114-related sequences so far isolated and was homologous to the corresponding region of replication-competent RD114 with regard to their restriction map and partial sequence analysis (p20). Otherwise, ECE2 had a deletion of approximately 1 kbp in the putative pol gene and, therefore, did not represent the locus of inducible RD114 virus. PMID- 2102653 TI - [Results of endocrinologic studies in culture media after coculture of bovine oocytes with granulosa cells]. AB - The steroid hormones progesterone (P.), and testosterone (T.) were radio immunologically determined in 108 medium samples, following co-culturing of bovine oocytes with granulosa cells. P. and T. values recorded from a control group were lower with significance than those recorded from co-culturing groups, that is 72 +/- 21 ng/ml and 264 +/- 84 pg/ml as compared to 208 +/- 138 ng/ml and 2,168 +/- 1,595 pg/ml in the oocyte plus fresh granulosa cell co-culturing group as well as 364 +/- 215 ng/ml and 825 +/- 233 pg/ml in the oocyte plus pre incubated granulosa cell co-culturing group. These rises were accompanied by decline in maturation rate, increase in oocyte degeneration, and rises in the rates of fertilisation and segmentation. PMID- 2102654 TI - [Birth weight, parturition and meat production in the dairy cow population]. AB - Birth weight was found to be closely related to calving behaviour. With all variations in Friesian dairy cattle, rising beef yield proved to be achievable even along with medium birth weight, so that calving complications and resulting decline in reproduction can be avoided. PMID- 2102655 TI - Effect of sera from acute lymphoblastic leukemia children on proliferation and differentiation of HL-60 promyelocytic leukemia cell line. AB - Influence of sera of children with ALL on character (dispersed or compact) and composition (granulocyte or macrophage) of colonies, formed from the human promyelocytic leukemia cell line HL-60, was estimated. An increased activities stimulating formation of dispersed G and M colonies was found in the sera of patients before therapy. Dynamics of colonies formation and their composition in the course of treatment point to some changes in the serum the levels of these activities with a tendency to full normalization in remission. PMID- 2102656 TI - Effects of retinoic acid on plasminogen activator activity and cellular proliferation. AB - This paper reports effects of retinoic acid (RA) on the expression of plasminogen activator (PA) activity and their relation to the effects of the vitamin on cellular proliferation. RA at the concentrations of 10 microM ml and 1 microM/ml did not affect PA activity in the cells of human melanoma cell line 10-135 but produced a transient decrease of PA activity as well in two other human melanoma cell lines as in RK 13 and IAR 6-7 cells. Unlike 10-135 cells which were resistant to retinoic acid all the remaining cell lines were susceptible to inhibition of the growth by the vitamin. Replacement of the medium with RA by standard medium produced a reversal of the inhibitory effects of the vitamin on PA activity and cell proliferation. PMID- 2102657 TI - Immunological profile of animals exposed to pesticide--deltamethrin. AB - The effect of deltamethrin (10- or 30-day exposure) on selected parameters of humoral and cellular immune response in mice was studied. In parallel also hematologic and histologic examinations were performed. It was found that deltamethrin exerts negligible immunotropic effect. The prevailing was suppressive effect, and in some cases also stimulatory effect (PFC, GvH, Il-1, exogenous CFU-s). This negligible activity on the immunological system may be attributed to low toxicity of deltamehtrin in relation to the cells of immunological system or to too short exposure of the animals to its effect. PMID- 2102658 TI - The effect of cyclophosphamide derivatives on cellular cytotoxicity (NK, ADCC) in vitro. AB - We have studied the effect of alkylating agents (AA): cyclophosphamide (Cy), 4 hydroperoxycyclophosphamide (4HCy), mafosfamide (MF), and nitrogranulogen (NTG) on cytotoxicity evaluated in ADCC and NK assays. While NK cells were sensitive to AA, higher concentrations of 4HCy and MF were necessary to affect killer cells active in ADCC assay. NTG which was without any effect on ADCC was found to be the most efficacious inhibitor on NK activity. PMID- 2102659 TI - The effect of adherent peritoneal exudate cells (APECs) and their products on the RPC-5 plasmacytoma growth in vitro. AB - The ability of peritoneal exudate cells (PECs) and their adherent (APECs) and nonadherent (NAPECs) fractions to enhance RPC-5 plasmacytoma growth in vitro was studied. The capability of these cells to bind RPC-5 cells and influence of the binding on cytolysis tumor cells by activated with C. parvum macrophages was also determined. The effector cells were harvested from mice injected i.p. with pristane, thioglicollate medium or C. parvum or from intact mice. The effect of supernatants from the in vitro cultured PECs, APECs or NAPECs on growth RPC-5 cells were also tested. It was found that the RPC-5 plasmacytoma growth was enhanced only by cells obtained from mice treated with pristane, or by supernatants from cultured PECs and APECs derived from pristane treated mice. The adherent cells from pristane treated mice were able to bind tumor cells. The tumor cells preexposed to adherent cells from pristane stimulated mice were resistant to lysis by activated with C. parvum macrophages. PMID- 2102660 TI - Methylcholanthrene-induced tumors in adult and in aging rats: infiltrating cells and their ADCC activity. AB - In our previous studies we found that the slower growth of syngeneic, immunogenic MC-induced sarcoma (MC-Sa) in aging rats was followed by the higher activity of spleen lymphocytes in ADCC assay. The purpose of the present paper was to study infiltrating cells of immunogenic and non-immunogenic MC-Sa and to estimate in situ ADCC activity in relation to the growth of MC-Sa transplants in adult and aging rats. It was found that MC-Sa's were infiltrated mainly by lymphocytes. Among cells infiltrating tumor the high percentage of cells with Fc receptor was present. During progressive tumor growth the percentage of infiltrating cells and also FcR+ cells significantly decreased within immunogenic MC-Sa, but did not change in the case of the non-immunogenic MC-Sa. In cell infiltrates of both tumors no differences between adult and aging rats were observed. At early stages of the tumor growth the cells active in ADCC assay were present within both MC Sa. The slower growth of immunogenic MC-Sa in aging rats compared with adults was connected with longer maintenance of ADCC activity in situ. In the case of non immunogenic MC-Sa, which grew at similar rate in both groups of rats, no differences in ADCC activity between adult and aging animals were observed. It is suggested that in situ ADCC activity may be one of the mechanisms responsible for the slower growth of immunogenic MC-Sa in aging rats. PMID- 2102661 TI - The effect of adherent peritoneal exudate cells on plasmacytoma growth in BALB/c mice. AB - The effect of adherent peritoneal exudate cells (APECs) from pristane treated and intact mice was studied by Winn's test. The experiments were performed with the use of plasmacytoma cell lines TEPC-15f, MP-26 and five primary lines. The studies showed that APECs from mice exposed to treatment with pristane were able to stimulate growth of both TEPC-15f and MP-26 plasmacytoma. The primary plasmacytoma lines adapted to intraperitoneal growth more easily in the presence of adherent cells than when they were given alone. PMID- 2102662 TI - Values of certain biochemical parameters in mouse serum after syngeneic bone marrow transplantation. Effect of various methods of myeloablation immunosuppression preparation and recipient's age. AB - In the mouse experimental model the effect of two different methods of myeloablation-immunosuppression treatment administered as preparation for bone marrow transplantation was studied, also the effect of animal's age on the values of the essential biochemical parameters in the serum and on the body weight of the animals was assessed. The recipients were prepared for the transplantation with total-body irradiation and administration of cyclophosphamide (radio chemotherapy) or administration of busulphan with cyclophosphamide (combined chemotherapy). Transplantation was done in animals aged 2.5 and 12 months. In all studied animals serum protein and calcium levels were decreased after the transplantation and the uric acid level was transiently raised. In the older mice a short lasting increase in the serum levels of bilirubin, alkaline phosphatase, AST and ALT was noted. However, no changes were found in the results biochemical investigations which could have been related to the method of myeloablation and immunosuppression, apart from slight hypercholesterolaemia which developed about 30 days after the operation in mice prepared by radio-chemotherapy. However, after a year lower body weight was observed in young mice prepared for the procedure with radiation exposure and cyclophosphamide, as compared to those receiving combined chemotherapy. Clinical aspects of these disturbances are discussed. PMID- 2102663 TI - Treatment of myofascial pain-dysfunction syndrome with occlusal equilibration. AB - Fifty-three patients with a diagnosis of chronic myofascial pain-dysfunction syndrome were treated with occlusal equilibration to establish complete anterior guidance. In approximately 5 to 7 days after treatment, most myofascial pain dysfunction symptoms disappeared and complete symptom resolution was usually attained within 3 weeks. The common symptoms all patients had were (1) pain and fatigue in the masseter and temporal muscles, (2) nocturnal bruxism, (3) jaw tension on waking up, and (4) difficulty chewing some foods. All patients had an absence of true anterior guidance with molar interferences in all excursive movements. Many patients had previously undergone orthodontic therapy and had "ideal" vertical tooth relationships. Treatment consisted of occlusal equilibration to remove all posterior interferences and establish anterior guidance. Three appointments, 1 week apart, were alloted for treatment. Major symptom reduction occurred after the first appointment. Four-year follow-ups reveal no recurrence of chronic symptoms after treatment completion. PMID- 2102664 TI - A simplified technique for fabricating esthetic cast metal occlusal surfaces for dentures. AB - This article describes a simplified method for making esthetic cast metal occlusal surfaces. Monoplane posterior acrylic resin block teeth, cast in a nickel-chrome alloy, are coated with silane and an esthetic composite resin veneer is applied to the buccal surface. These veneered posterior metal teeth are incorporated in the wax setup and the dentures are processed and finished. The dentist's routine technique for delivering dentures to the patient can be followed. PMID- 2102665 TI - Formulation and dosage form design in drug-induced topical irritation of the gastrointestinal tract. AB - To test drugs for topical effects on gastrointestinal mucosa, a new in situ rabbit colon model was used that permits direct application of drugs in suspensions from gel cups, solutions, or commercially available tablets and capsules onto rabbit colonic mucosa for up to 8 hr. For each agent tested an irritation index was calculated--the product of the area of the mucosa affected by drug exposure and a numerical score for observed effect. Irritation indices ranged from 0 (no effect) to 25.6 (maximal irritation measurable). In general, the immediate release of drug onto tissue elicited the greatest effect, whereas slow or controlled release of drug produced the least response. Topical irritation was found to be a function of (1) the drug, (2) the formulation, (3) the delivery rate, and (4) the concentration. The gastrointestinal therapeutic system (GITS) of potassium chloride and of brompheniramine/pseudoephedrine produced far less irritation than current commercial formulations of these drugs. The rabbit colon model is proposed as a useful screening tool during drug development to aid in selecting the formulation of an oral dosage form that will minimize topical irritation. PMID- 2102666 TI - Complications of small intestinal biopsy in hypoalbuminemic dogs. AB - The records of 30 dogs that were hypoalbuminemic and had undergone full-thickness biopsy of the small bowel, and the records of 22 dogs with normal albumin levels and small bowel biopsy, were reviewed. Plasma albumin concentrations for the former group were 30 to 93% of contemporary normals. There were no serious healing difficulties in the hypoalbuminemic dogs during the 7 day postoperative period examined. Nine dogs developed mild to moderate truncal and peripheral edema. The most common occurrences in the dogs with normal plasma albumin levels were edema and seroma formation adjacent to the skin incision. There was one death resulting from peritonitis subsequent to enterotomy dehiscence. Another dog developed peritonitis even though biopsy sites were intact when examined at a second surgery. PMID- 2102667 TI - Unusual thyroid scintigrams in Plummer's disease during methimazole therapy. Conversion of hot to hypofunctional nodules. AB - Thyroid scintigrams of two women (aged 48 and 58) with Plummer's disease showed unusual radioiodine accumulation during treatment with methimazole (MMI). Before MMI therapy, the scintigrams revealed most of the radioiodine uptake only in the nodules of the patients and very little uptake in the non-nodular portions of the thyroid. After initiation of MMI therapy, scintigrams performed at three and eight months revealed that the hot nodules had become hypofunctional and that the surrounding tissues had normal radioiodine accumulation. The findings indicate that the nodules in Plummer's disease continue to concentrate MMI selectively compared with normal surrounding thyroid tissue during therapy. PMID- 2102668 TI - The effect of prescribed daily dose frequency on patient medication compliance. AB - The objective of this study was to determine the relationship between prescribed daily dose frequency and patient medication compliance. The medication compliance of 105 patients receiving antihypertensive medications was monitored by analyzing data obtained from special pill containers that electronically record the date and time of medication removal. Inaccurate compliance estimates derived using the simple pill count method were thereby avoided. Compliance was defined as the percent of days during which the prescribed number of doses were removed. Compliance improved from 59.0% on a three-time daily regimen to 83.6% on a once daily regimen. Thus, compliance improves dramatically as prescribed dose frequency decreases. Probably the single most important action that health care providers can take to improve compliance is to select medications that permit the lowest daily prescribed dose frequency. PMID- 2102669 TI - Posttraumatic gustatory rhinorrhea. AB - We describe a case of gustatory rhinorrhea in which gustatory stimuli caused nasal obstruction and secretion simulating cerebrospinal rhinorrhea. This disorder was presumably caused by faulty regenerated parasympathetic nerve fibers reaching the nasal mucosa or, possibly, by a congenital condition. The characteristics of this disorder are compared with other autonomic disorders of the head and neck. PMID- 2102670 TI - Personality styles of patients asserting environmental illness. AB - Case reports and chart reviews of patients asserting environmental illness suggest that they suffer from psychiatric difficulties, typically somatization disorder. We assert that viewing these patients solely as somatizers or hysterical characters searching for a nurturant relationship will undermine the doctor-patient relationship. Rather, many of these patients are obsessive/paranoid characters searching for a medical explanation to their physical symptoms. This distinction is highlighted by contrasting the clinical presentations of hysteric/somatizing patients with those environmental illness patients demonstrating an obsessive/paranoid style. Further illustration is provided by a case report with psychological test data. Finally, treatment recommendations based upon this distinction are delineated. PMID- 2102671 TI - Fluoxetine treatment of anorexia nervosa: an open clinical trial. AB - Six patients with chronic, refractory anorexia nervosa were treated with fluoxetine. Depressive symptoms diminished in all patients, and this was associated with weight gain. Subjects, despite frequent medical comorbidity, tolerated fluoxetine well, even in dosages greater than those used for depression. PMID- 2102672 TI - Randomized, prospective study of nail bed ablation for recurrent ingrowing toenails. AB - A consecutive series of 31 recurrent ingrowing toenails, which had previously undergone at least two surgical procedures, were recruited to this study over a 1 year period. Patients were randomly allocated to one of two treatment groups. Group A underwent nail bed excision whilst group B had nail bed phenolization in addition to excision. Patients were reviewed 2 weeks and 1 year after operation. Seven toes (41%) in group A developed postoperative infection compared with only one (7%) in group B (P less than 0.01). Recurrent nail spicules occurred in ten patients (59%) in group A and six patients (43%) in group B 1 year after operation. High failure rates for ablation of recurrent ingrowing toenails should encourage greater efforts towards adequate treatment at the first presentation. PMID- 2102673 TI - A retractor for cholecystectomy. AB - A self-retaining retractor has been designed to enable one surgeon to perform cholecystectomy and exploration of the bile duct with a minimum of assistance. The instrument consists of a horseshoe shaped collapsible frame and four specially designed blades. It is ideally suited for a right subcostal or a transverse incision. Adjustment and removal for performing on-table cholangiography and reapplication are all straightforward. PMID- 2102674 TI - Carbamazepine and forme fruste neuroleptic malignant syndrome. AB - A woman developed rigidity, autonomic instability and altered consciousness after taking an overdose of trifluoperazine and carbamazepine. A diagnosis of NMS was made despite the absence of fever, as carbamazepine might modify the presentation of NMS. PMID- 2102675 TI - Purity determination by a combination of spectrophotometric and liquid chromatographic methods: application to 13-cis-retinoic acid. AB - A method is described to determine the purity of 13-cis-retinoic acid. Spectrophotometry is used to determine the non-UV-absorbing impurities, and HPLC is used to determine the UV-absorbing impurities. In combination, these methods permit determination of the purity. An authentic standard is used in developing this method, but it is not needed in the application of the method. PMID- 2102676 TI - More about vasectomy. PMID- 2102677 TI - Origin and spread of AIDS. PMID- 2102679 TI - High frequency oscillation and tracheobronchial clearance. PMID- 2102678 TI - A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. AB - Mitochondrial encephalomyopathies are usually divided into three distinct clinical subgroups: (1) mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS); (2) myoclonus epilepsy associated with ragged red fibres (MERRF); and (3) chronic progressive external ophthalmoplegia (CPEO) including Kearns-Sayre syndrome. Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNALys gene give rise to CPEO including Kearns-Sayre syndrome and MERRF, respectively. Here we report an A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNA(Leu)(UUR) that is specific to patients with MELAS. Because this mutation creates an ApaI restriction site, we could perform a simple molecular diagnostic test for the disease. The mutation was present in 26 out of 31 independent MELAS patients and 1 out of 29 CPEO patients, but absent in the 5 MERRF and 50 controls tested. Southern blot analysis confirmed that the mutant DNA always coexists with the wild-type DNA (heteroplasmy). PMID- 2102680 TI - Radionuclide esophageal transit study in detection of esophageal motor dysfunction: comparison with motility studies (manometry) AB - Radionuclide esophageal transit study (RETS) has been developed to assess motor function of the esophagus. The purpose of this study was to compare RETS to esophageal motility studies (EMS) in detection of motility disorders. A total of 109 consecutive patients without previous history of surgery on the esophagus underwent both RETS and EMS within one month of each other. Final diagnosis was divided into three categories: I--primary esophageal motor disorders (n = 39); II -reflux disease (n = 48); and III--non-cardiac chest pain and/or dysphagia (n = 22). Using EMS as the standard, the results of RETS were as follows: sensitivity for detection of motor dysfunction was 97%, 92%, and 77% for Groups I, II, and III, respectively, while specificity was 91% for Group II and 100% for Group III. Global sensitivity was 92% and specificity was 88%. No clinically significant motor disorders were missed by RETS. In conclusion, RETS is a useful noninvasive test for the screening of patients with symptoms thought to be of esophageal origin. PMID- 2102681 TI - Diarrhoea--differential diagnosis. AB - Diarrhoea may present as an acute or chronic illness. The causes are numerous, and can usually be determined by consideration of the mechanics of the diarrhoea, the site of the disease process and its nature. A careful history and physical examination are essential, followed by appropriate investigation. PMID- 2102683 TI - Retrobulbar block: a review for the clinician. AB - Recent improvements in technique have made cataract surgery a popular procedure in the outpatient setting. One of those advances has been the use of retrobulbar block instead of general anesthesia. This article explains the anatomy, pharmacology, technique and complications of retrobulbar block. PMID- 2102684 TI - Ethnic minorities and the psychiatric system. PMID- 2102682 TI - Characterization of a second highly conserved B-type lamin present in cells previously thought to contain only a single B-type lamin. AB - Previous analyses of the nuclear lamina of mammalian cells have revealed three major protein components (lamins A, B and C) that have been identified by protein sequence homology as members of the intermediate filament (IF) protein family. It has been claimed that mammalian cells contain either all three lamins or lamin B alone. Using monoclonal antibodies specific for B-type lamins and cDNA cloning we identified a second major mammalian B-type lamin (murine lamin B2), thus showing that lamin composition in mammals is more complex than previously thought. Lamin B2 is coexpressed with lamin B1 (formerly termed lamin B) in all somatic cells and mammalian species that we analysed, including a variety of cells currently believed to contain only a single lamin. This suggests that two B-type lamins are necessary to form a functional lamina in mammalian somatic cells. By cDNA cloning we found that Xenopus laevis lamin LII is the amphibian homolog of mammalian lamin B2. Lamin expression during embryogenesis of amphibians and mammals shows striking similarities. The first lamins expressed in the early embryo are the two B-type lamins, while A-type lamins are only detected much later in development. These findings indicate that the genomic differentiation into two B-type lamins occurred early in vertebrate evolution and has been maintained in both their primary structure and pattern of expression. PMID- 2102685 TI - The hot clot sign. A new finding in deep venous thrombosis on bone scintigraphy. AB - Focal Tc-99m MDP uptake on bone scanning in regions of deep venous thrombosis (DVT) is reported in two patients with documented DVT. It is speculated that this uptake may be related to localized calcification or ossification, which is occasionally observed on radiographs of patients with chronic DVT. PMID- 2102686 TI - Black deaths in custody. PMID- 2102687 TI - Pharmaceutical promotion. PMID- 2102688 TI - Methadone maintenance therapy. PMID- 2102690 TI - Repair of iris coloboma by a closed chamber technique. PMID- 2102689 TI - Management of intrameatal warts in men. PMID- 2102691 TI - Developing a hospital nursing research program. AB - Including nursing research as a stream in the nursing career structure in Western Australia paved the way for development of the Nursing Research Department at Sir Charles Gairdner Hospital. Over the last two years a program of research activities has been introduced to assist nurses to evaluate their practice, to critique the research and apply its results in patient care. PMID- 2102692 TI - A collaborative approach to nursing field placement. AB - The numbers of nursing students undertaking pre-registration education in higher education courses in South Australia has expanded rapidly over the last four years. This paper describes collaboration between Schools of Nursing to coordinate student placements in clinical venues. A computerised system has been developed which is unique in Australia and its positive results are identified. PMID- 2102693 TI - Occupational stress and RANs. AB - This paper explores nurses' self-reported stress during a time of policy changes in the Northern Territory Health Department. It is argued that current research tends to associate nurses' stress with their personality or type of work, offering a psychological or occupational explanation. Little consideration is given to the complex structural subordination and ambivalence remote area nurses experience on Aboriginal settlements vis a vis their immediate superiors and clients. It is proposed that the nurses' self-reported stress can be partly accounted for by their marginal position between these two groups. The sociological concept of marginality can explain this. PMID- 2102694 TI - "Well, was it worth it?" The value of teletutorials for bachelor of nursing students. AB - The Deakin University Faculty of Nursing conducts a Bachelor of Nursing degree which is available via the distance education mode. The faculty has as its central focus the value of nursing practice and espouses a belief in students' active learning. This paper examines the use of teletutorials as a process for realising the philosophy of the faculty in relation to students' learning outcomes. Although expensive in terms of financial and human resources, teletutorials bridged the gap between the faculty's philosophical statements and students' perceptions and needs. PMID- 2102695 TI - Whiter than white? Clean and healthy? A new challenge for nurses. AB - As primary health care workers nurses should be encouraged to see their role as encompassing a concern with and responsibility for the environment that is consistent with an holistic conception of health or wellness. It is argued that health care workers and environmentalists (who may be one and the same) need to carefully consider issues surrounding a sustainable environment. Building alliances with unions and the community, as occurred in the Green Ban Movement in New South Wales in the early 1970s, would be useful. The debate surrounding future plans for the timber industry illustrates the strategic importance of trying to change consumer demand in ways which can make better resource management and production practices commercially viable. This paper argues against simplistic responses to the conversation crisis and emphasizes the need to strike a balance between environmentalism and the avoidance of mass unemployment, itself a source of ill-health. PMID- 2102696 TI - Developing a model for collaborative research. AB - Collaboration between nurses in clinical and educational settings has been advocated as a means of ensuring nursing research is both practice oriented and scientifically valid. This paper describes a model, jointly developed by colleagues from the Nursing Departments of Alfred Hospital and La Trobe University, to foster collaborative research and steer research projects generated by clinical nurses from conceptualisation to publication. PMID- 2102697 TI - Adapting to diabetes: metabolic control and psychosocial variables. AB - The purpose of this study was to examine the influence of hardiness, self efficacy, coping style and psychosocial adaptation to illness on the metabolic control of insulin dependent and non-insulin dependent subjects. After adjustment for age, gender and diabetes type the best predictors for insulin dependent diabetics were found to be hardiness and psychosocial adjustment, and for non insulin dependent diabetics, psychosocial adjustment alone. No interaction effect was found between the variables. Self-efficacy and coping skills were not found to predict metabolic control. PMID- 2102698 TI - [Mucolytic therapy: a new product]. PMID- 2102699 TI - [Absorption, distribution, excretion and metabolism of 4-carbomethoxythiazolidine chlorohydrate. Biochemical experimental study in the rat]. AB - A biochemical-metabolic study has been conducted on TCM (4 carbomethoxythiazolidin hydrochloride) in rats, utilising a product traced with 14C. An in-vitro test has demonstrated that TCM is hydrolised by endogenous esterases to thiazolidincarboxylic acid, into the following decreasing order of activity: kidneys, lungs, plasma, liver, intestinal content and mucosa. Upon oral administration, TCM proved to have a good and rapid absorption and distribution level in the organs. In the beginning the liver and the kidneys have displayed higher concentrations with respect to the lungs; after 8 hours, however, the latter have displayed slightly lower concentrations than before, which were not very far from the liver's and kidneys'. TCM has been mainly eliminated through the urines (56.9% in 24 hours) and less through the feces (6.7% in the same period of time). By means of a thin-layer chromatography analysis and a mass spectrometry it has been possible to study the metabolism of TCM. The results of both in-vitro and in-vivo tests have demonstrated that TCM is hydrolised to thiazolidin-carboxylic acid, which, in its turn, is transformed into cysteine. This last transformation does mainly occur in the liver, but significantly in the lungs as well. TCM is absorbed in part as such and in part as thiazolidincarboxylic acid. As no methyl-cysteinate has been traced, it has been assumed that the hydrolysis of the ester bond was a kinetically quicker event than the heterocycle opening. PMID- 2102700 TI - [Metabolism of 4-carbomethoxythiazolidine chlorohydrate to cysteine through human expectorate and lung homogenates, and its action on glycoproteins of mucus]. AB - A study has been carried out on the formation of -SH groups and of cysteine and cystine from 4-carbomethoxythiazolidin HCl through human expectorate mucus and lung homogenates. Both the expectorate and the homogenate, revealed to be able to metabolize TCM to cysteine releasing free -SH groups. The speed of cysteine formation is higher for the homogenate, but also the expectorate revealed to be very effective for the metabolization to cysteine. Furthermore it has been demonstrated that the TCM, incubated with human expectorate in presence and in absence of lung homogenate, can modify the chemical-physical characteristics of the mucus, rendering it more soluble and less viscous, i.e. displaying a mucolytic activity. These results account for the in-vitro experimental base to the observation that the product has a mucolytic activity whether administered by os or by aerosol. PMID- 2102701 TI - [Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate in combination with antibiotic and bronchoactive therapy in adult patients with acute and chronic bronchopneumopathy with prevalent exudative component]. AB - 20 patients, aged between 31 and 71, have been treated. All were hospitalized because of acute or chronic broncho-pneumopathy and have been administered 4 carbomethoxythiazolidine at a dosage of 300 mg/d. in association with the common antibiotic or chemiotherapic treatments. Every day all symptoms have been registered (asthenia, cephalea, sibiluses, rhoncuses, rales, inspiratory and expiratory dyspnea). Before and after the treatment some respiratory functioning tests have been performed, including the VEMS and VEMS/CV determination. A further study on the distribution of the inhaled air has been carried out, as well as on the ventilation/perfusion ratio by means of He and CO2 curves. At the beginning and at the end of the TMC treatment some hematiobiologic tests have been carried out, including: haemochromo with leukocytic formula, blood platelets counting, VES, glycemia, azotemia, transaminase, alkaline phosphatase, total bilirubinaemia, prothrombinic activity and determination of urine's specific weight. The pulmonary symptomatology (cough, sibiluses, rhoncuses, rates, inspiratory and expiratory dyspnea), was markedly reduced. Even if, as for the preliminary character of the experiment, we can state that 4 carbomethoxythiazolidine is a drug with an outstanding level of tolerance. PMID- 2102702 TI - [Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate administered by aerosol in adult patients with catarrhal pathology of otorhinolaryngologic origin]. AB - The test has been performed on 20 patients, aged between 14 and 68 suffering from a catarrhal pathology of otorhinolaryngologic nature for which a mucolitic aerosol therapy was recommended. 4-carbomethoxythiazolidine has been administered with a posology of one bottle twice a day (by aerosol-nebulization) for periods of time ranging from 4 up to 15 days. Together with the 4 carbomethoxythiazolidine treatment, some patients have been administered concomitant drugs. At the end of the tests the development of the most significative symptomatologic parameters has been analysed according to the Wilcoxon test: quantity, kind and characteristics of nasal secretions, nasal obstruction, phlogosis of the nasal and pharyngeal mucosa, hoarseness, difficulty in catarrhal expectoration, hypoacusia, retraction of the tympanic membrane. The final clinic evaluation of the efficacy of 4-carbomethoxythiazolidine, expressed according to the examination of the achieved clinic result, has been "positive" in 17 cases (85%) and "negative" in 3 cases (15%). As for its tolerance, in no case has 4-carbomethoxythiazolidine caused detectable side-effects. PMID- 2102703 TI - [Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate in adult patients with hypersecretory bronchopulmonary diseases]. AB - 40 patients suffering from acute hypersecretive bronchopulmonary disorders were treated for a period of 6-9 days. They have been administered 4 carbomethoxythiazolidine both in capsules and in granular form at a dosage of 400 mg/day. At the beginning of the treatment with 4-carbomethoxythiazolidine (basal stage) after 3-4 days and at the end (final stage) the following clinic parameters have been registered: presence and quantity of the expectoration, difficulty in expectoration, signs of bronchial hypersecretion detectable by thorax auscultation, cough. At the basal and final stages the haematochemical parameters have been determinated such as: haemoglobin, azotemia, SGOT, SGPT, read corpuscles. They did not show individual or average variation over the values registered at the basal stage. At the end of the experiments collected data, biometric elaboration by Wilcoxon test has been carried out. The conclusive judgement on the efficacy of 4-carbomethoxythiazolidine, has been positive in 95% of the cases. PMID- 2102704 TI - [Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate in a double-blind crossover experiment on chronic obstructive bronchopneumopathy]. AB - The Authors describe a test performed on 20 hospitalized patients aged between 22 and 80, suffering from obstruent chronic broncho-pneumopathy. The test has been performed according to a double-blind pattern; each patient has been treated according to the 10-day long randomized scheme with one of the two drugs N-acetyl L-cysteine, 4-carbomethoxythiazolidine. After a 7-day wash-out the patient has been treated with the other drug for a further period of 10 days. All patients have been administered both products at a dosage of 200 mg. three times a day. Every day following values have been registered: arterial pressure, body temperature; subjective and objective symptomatology relieves: cough, cephalea, asthenia, sibiluses, rhoncuses, rales, inspiratory and expiratory dyspnea. Furthermore before and after the treatment the quantity and the quality of the expectorate in order is evaluate the biologic tolerance of the examined drugs, before and after each treatment the following haematochemical and urinary tests have been performed: VES, azotemia, glycemia, SGOT, SGPT, LDH, alkaline phospatase, total and direct bilirubinaemia, prothrombinic activity, complete chemical analysis of urines. As shown in Tab. I-IX, a global analysis of the results proves that 4-carbomethoxythiazolidine is a very well-tolerated drug without any negative side-effect. As far as its therapeutic efficacy is concerned we can say that the mucolitic activity of 4-carbomethoxythiazolidine is the some of that of N-acetyl-L-cysteine. PMID- 2102705 TI - [Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate in patients with exacerbated chronic bronchitis]. AB - 4-carbomethoxythiazolidine HCl has been administered to 24 patients (aged between 64 and 86) suffering from new acute stages of chronic bronchitis. The patients have been submitted to a double-blind test and have been subdivided into four groups; each of them was administered a placebo or the a.m. product. Dosage: 200, 400 and 600 mg/d. The following symptoms have been evaluated: cough; dyspnea; bronchial breathings; expectoration; expectorate's viscosity; expectorate's volume. The data have been submitted to a statistic analyses, this research leads to the followings considerations. A dosage of 200 mg/d. is not significantly active on any on the considered parameters. The 400 mg dosage turns out to be noticeably more effective than the placebo on all parameters (except the difficulty in expectoration). A dosage of 600 mg/d. has a significant effect on all the measurable parameters. Finally, a 200 mg dosage of 4 carbomethoxythiazolidine three times a day results to be the best posology in the symptomatic treatment of the respiratory manifestations of chronic bronchitis. PMID- 2102706 TI - Special focus on the biology of aging. PMID- 2102707 TI - Overview of biological mechanism of aging. PMID- 2102708 TI - Altered protein metabolism in aging. PMID- 2102709 TI - Skeletal muscle weakness and fatigue in old age: underlying mechanisms. PMID- 2102710 TI - Vulnerability of the neuronal cytoskeleton in aging and Alzheimer disease: widespread involvement of all three major filament systems. PMID- 2102711 TI - Dietary restriction as a probe of mechanisms of senescence. PMID- 2102712 TI - Role of endogenous proteins as negative growth modulators during in vitro cellular aging of human diploid fibroblasts. PMID- 2102713 TI - T-cell function in aging: mechanisms of decline. AB - The above sections have provided numerous facts, many of which are conflicting, regarding the changes that occur with increasing age in T lymphocytes. Although it is impossible to state with absolute certainty the alterations that are responsible for decreased proliferation of lymphocytes from elderly subjects, the following summarizes the current status of the data: 1. The interaction of T lymphocytes with foreign stimuli appears to be generally intact. 2. Changes in numbers of CD3+, CD4+, or CD8+ cells before interaction with foreign stimuli or in the density of these markers or of mitogen receptors on the surface of aged T cells have not been consistently observed. When reported to occur, the changes are not sufficient to account for the significant decrease in T-cell proliferation that occurs with increasing age. 3. A defect in the ability of the membrane interaction with foreign stimulus to signal subsequent internal events may occur, because stimulation with phorbol esters and calcium ionophore can result in increased proliferation in some elderly subjects. 4. Decreased accumulation of cytosolic calcium after stimulation of elderly T cells occurs in mice and may be a major component of the defective activation system. This defect appears to be most apparent in the "memory" T cells (T cells expressing high levels of Pgp-1), which increase in number with increasing age. Decreases in Ca++ accumulation have not been observed in humans, but this may be due to different stimuli used. Further, investigation of an increase in "memory" T cells and of their inability to mobilize Ca++ has not been done in humans and rats. 5. Decreases in mRNA for c-myc, IL-2 receptor, and IL-2 have been reported in some, but not all, species. Whether these decreases are the result of decreases in Ca++ mobilization or are independent events in unknown. 6. Decreases in membrane expression of the activation marker RL388 and of TfR have been reported. 7. Lymphokines: a. Decreases in IL-2 production occur in mice and humans, but not in rats. In individuals with decreased IL-2 production, addition of exogenous IL-2 totally restores proliferative ability in only some individuals. Changes in IL-2R expression (number or affinity) may be an additional defect. b. Decreases in IFN gamma occur in humans, but not in mice or rats. c. No change in IL-1 occurs in any species. Genotypic effects must be considered when evaluating the preceding observations. The heterogeneity among individuals, even within an inbred strain, cannot be discounted.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2102714 TI - Molecular genetic approaches to mechanisms of senescence. PMID- 2102715 TI - [Vomiting induced by chemotherapy: the current outlook]. PMID- 2102716 TI - [Antiemetic treatments associated with antineoplastic chemotherapy]. AB - 56 female patients with breast carcinoma and treated with polychemotherapy: adriamycin, vindesine, ciclophosphamide and 5-fluorouracil were studied, divided in three groups with different antiemetic schedule: group A 40 mg/iv of metoclopramide; group B 40 mg iv of metoclopramide and 125 mg/iv of methylprednisolone before beginning chemotherapy; and group C 2 mg/oral of lorazepam, 125 mg/iv methyl-prednisolone and 1 mg/kg/oral of metoclopramide previously to begin chemotherapy; at two and four hours of the first dose, metoclopramide was repeated the same doses (really) three doses each two hours. The combination of methylprednisolone-metoclopramide (B), decreases significantly the intensity, duration and frequency of nausea and vomiting, achieving total protection (no vomiting) in 4.34% of cycles of chemotherapy in group A, 32.2% in group B and 30.2% in group C (p less than 0.005 group A versus group B and A versus group C). Also we observed, without statistical analysis, better subjective tolerance to chemotherapy in patients receiving lorazepam associated to schedule B (schedule C). This makes it the recommended schedule. PMID- 2102717 TI - [Changes in the glycolytic pathway in patients with essential arterial hypertension]. AB - The defect of the sodium pump of the blood cell membrane in patients with essential blood hypertension, can induce changes in the metabolic use of ATP, especially at glucolytic pathway level. We studied the blood levels of ATP (32.51 +/- 10.80 mg/100 ml), 2,3-DPG (0.82 +/- 0.47 mumol/ml), piruvate (0.36 +/- 0.16 mg/100 ml) and lactate (18.88 +/- 4.53 mg/dl), of a group of 50 patients with essential blood hypertension and of 50 healthy persons in the control group (17.09 +/- 6.37 mg/100 ml, 0.45 +/- 0.23 mumol/ml, 0.33 +/- 0.15 mg/100 ml and 17.32 +/- 3.85 mg/dl respectively). There were statistically significant differences between ATP (p less than 0.0005) levels and 2,3-DPG and lactate (p less than 0.05). These results force us to study the presence of those changes on peripheral tissues to see whether they play an important role in hypertension complications, especially in respect of the vascular wall. PMID- 2102718 TI - [Renal digital angiography in the study of hypertensive patients]. AB - 50 patients, 31 male and 19 female with mean age of 45.1 +/- 9.4 years afflicted with blood hypertension (BH) were studied. RDA was performed on all of them as part of the etiological study. The variables evaluated were: systolic blood pressure (SBP), diastolic blood pressure (DBP), therapy index (TI), evolution time of its BH and type of BH (refractory BH, severe BH, mild-moderate BH). The organ affliction was also evaluated (renal function, ECG, presence of cardiomyopathy, vascular disease, and retinopathy. RDA alteration appeared in 16 cases, 1 (10%) in refractory BH group, 8 (28.6%) in severe BH group, and 7 (58.3%) in mild-moderate BH group. A shorter BH evolution period having been observed in patients with altered RDA than in those with normal RDA (3.49 +/- 3.96 years vs 6.93 +/- 4.68 years p = 0.01). We conclude that only this variable is a feature for suspicion of renovascular BH, without an apparent difference between the results of RDA and those of I.V. urography, obtained during the diagnosis screening. The significant differences observed between the mild moderate BH and the other groups suggests that the clinical suspicion, and not the severity of the BH, is the point which should determine the patients to be renovascularly explored. PMID- 2102720 TI - [Myocardial infarct in diabetes mellitus patients. A long-term follow-up]. AB - The acute phase and long-term evolution of 249 patients diagnosed as having acute myocardial infarction and admitted to our hospital during the period 1981 to 1983, were studied. They were classified in 2 groups: A (non-diabetic patients) and B (diabetic patients). Several variables were analysed in order to determine the differences between both groups. The most accentuated being: diabetic patients, female sex, old age, blood hypertension history, cardiac failure, re extended infarction. The inter-hospital mortality was higher in group B, mainly as a result of cardiogenic shock and left cardiac failure. An out-patients follow up of acute phase survivors was carried out, between 1 to 96 months, with mean follow-up of 46.7 month in group A and 38.4 in group B, at 8 years the actuarial rate being 77.3% and 55.9% respectively. We conclude that diabetic patients with myocardial infarction register a higher long- and short-time mortality. PMID- 2102719 TI - [The role of prostacyclin and thromboxane in the antihypertensive action of enalapril]. AB - Enalapril produces an inhibition of the angiotensin-renin system, correlating the pre-therapy plasmatic renin activity with blood pressure decrease, during its administration. This does not always happen, data to the contrary existing in literature, suggesting that there are some other acting mechanisms. We studied 34 hypertensive patients, whose blood pressure levels were controlled by Enalapril at a mean dosage of 12.32 +/- 0.9. Determining plasmatic concentration of 6-keto PGF1a (a prostacyclin metabolite), T x B2 (a thromboxane A2 metabolite), their distribution, plasmatic renin activity and a radiological and biochemical study. We found a significant increase in their distribution and plasmatic renin at the end of the essay. The results suggest a possible double active mechanism: angiotension-renin and prostaglandins systems, owing to the imbalance occurring between prostacyclin and thromboxane, the first named being the most favoured. This, together with easy application and the lack of side effects, made this drug useful for treatment of blood hypertension. PMID- 2102721 TI - [Microangiopathic hemolytic anemia associated with breast cancer]. AB - A case of microangiopathic hemolytic anemia associated to metastatic breast cancer, in remission with chemotherapy, is presented. We review the etiopathogenetic mechanism of its association and focus on the priority of neoplasia therapy when disseminated intravascular coagulation is not present. PMID- 2102722 TI - [Charcot-Marie-Tooth: a family case report]. AB - Three cases in a Spanish family are presented, showing diagnosis criteria of hereditary motor-sensitive neuropathy (Charcot-Marie-Tooth disease) type I: suggestive symptoms, neurological and anatomopathological findings. The current classification of this pathology. PMID- 2102723 TI - [Undifferentiated bronchopulmonary carcinoma associated with scleroderma and hypertrichosis lanuginosa. A case report]. AB - The development of a malignant tumor, as well as hypertrichosis lanuginosa as a paraneoplasic syndrome, in a patient afflicted with scleroderma is a very rare event. We present the clinical history of a patient afflicted with scleroderma, non-differentiated bronchopulmonary carcinoma adn hypertrichosis lanuginosa as paraneoplasic expression of the tumor. PMID- 2102724 TI - [Peritoneal mesothelioma: the importance of ultrastructural study. A report of 2 cases and a review of the Spanish literature]. AB - Two cases of peritoneal mesothelioma (PM), with ultrastructural study, of females who lived in a rural area without asbestos exposition history are described and the Spanish literature reviewed. We highlight the association with severe autoimmune hemolytic anemia, due to the presence of cold agglutinins, in one patient without relationship to drugs or concomitant diseases. We focus on the need for thorough and multiple biopsies through laparoscopy to avoid false negative. We believe that there are no totally specific morphological data on mesothelioma, which means that the initial study is based on optical microscopy performed with hematoxylin-eosin and PAS-diastase stain using the electronic microscopy to confirm the diagnosis. PMID- 2102725 TI - [The etiopathogenesis of benign intracranial hypertension]. PMID- 2102726 TI - [Hemolytic anemia and alphamethyldopa]. PMID- 2102727 TI - [Primary diffuse large-cell mediastinal lymphoma with sclerosis]. PMID- 2102728 TI - [Alveolar proteinosis: a report of a case treated by total bronchopulmonary lavage]. PMID- 2102729 TI - [Miliary tuberculosis associated with cold agglutinin anemia in a patient with a history of chronic malaria]. PMID- 2102730 TI - [Asthma and hyperthyroidism: a dangerous association]. PMID- 2102731 TI - [Osteocalcin, 24,25(OH)2D and Paget's disease]. PMID- 2102732 TI - [The correlation between the serum levels of osteocalcin and 24,25 dihydroxyvitamin D in Paget's disease of bone]. AB - The influence of 24,25-dihydroxyvitamin D on different seric levels of osteocalcin in Paget's disease of the bone and in 11 of the control group, other parameters were also determined such as: seric levels of calcium, phosphate, parathormone, osteocalcin, 25-hydroxyvitamin D an 1,25 dihydroxyvitamin D. We observed that patients with Paget's disease showed increased or normal levels of seric osteocalcin, despite the high bone remodelling and significantly low level of 24,25-dihydroxyvitamin D observed in patients with high levels of osteocalcin. At the same time, we noticed a negative lineal correlation between both parameters. We suggest that 24,25-hydroxyvitamin D can be one of the important factors in producing increased or normal levels of osteocalcin in patients with Paget's disease of the bone. PMID- 2102733 TI - [Thyroid function study in patients with diabetes mellitus]. AB - We study 48 compensated diabetic patients, 41.6% of whom were male, 68.75% had diabetic neuropathy and/or vascular complications (macro-microangiopathy). In 60.4% of the patients the study began at ten years of disease evolution. We selected 14 healthy adults as a control group, 50% being male. Plasma levels of T3, T4 and TSH were measured by RIA and the antimicrosomal antibody (AMT) and antithyroglobulin antibody (ATG), detected by passive hemagglutination. A significant decrease in T3 level (p less than 0.05) was found in controlled diabetic patients, compared to T3 levels of the control group; there was a significant reduction in T3 level (p less than 0.05) in diabetic patients with vascular disease and in female diabetics (p less than 0.05), compared to the control group. There were no statistically significant differences in the other groups, including other parameters measured. We concluded that there is a decrease of T3 in all diabetic patients, this being more noticeable in diabetic females and diabetic patients with vascular disease. PMID- 2102734 TI - [The hypolipemic effect of concentrated salmon oil rich in n-3 fatty acids]. AB - The lipid-lowering effect of a concentrated salmon oil, rich in n-3 fatty acids was tested as a supplement to the normal diet of 27 patients with high levels of cholesterol and/or triglycerides, during 2 months. The results of the study confirmed that addition of n-3 fatty acid to diets produced a reduction of plasma levels of lipids. The most significant reduction of plasma levels of lipids. The most significant reduction was observed in triglycerides in patients with high levels (from 295.8 to 219.8 mg/dl) (p = 0.001), as well as the whole group (from 231 to 180 mg/dl) (p = 0.002). At the same time, there was a reduction of cholesterol in all patients (from 295 to 268.4 mg/dl) (p = 0.001), including those whose cholesterol was higher (from 316.2 to 284.9 mg/dl) (p = 0.002). We concluded that the use of compounds rich in n-3 fatty acids showed an important plasma lipid-lowering effect, playing a significant role in hyperlipidemic patient control. PMID- 2102735 TI - [Buerger's disease starting in the upper extremity. A favorable response to nifedipine treatment combined with stopping tobacco use]. AB - A case of a 38-year-old smoker male who had vasoconstriction and instep claudication of the right hand, is presented. After a year of evolution, he experienced the same alteration on the left foot. He was diagnosed as suffering from thromboangiitis obliterans, by means of angiography. After oral nifedipine treatment, combined with cessation of smoking, all symptoms and trophics regressed. PMID- 2102736 TI - [Pulmonary fibrosis and autoimmune manifestations. A diagnostic problem]. AB - A case of 54-year-old male who, during the development of a pulmonary fibrosis, showed extrapulmonary autoimmune symptoms (polyarthritis and hemolytic anemia), is presented. The antinuclear antibodies and rheumatoid factor positives have been described in up to 30% of the idiopathic pulmonary fibrosis, complicating the differential diagnosis with lung fibrosis caused by alterations of connective tissue. We discuss the prognosis and treatment of this difficult diagnosis. PMID- 2102737 TI - [Epithelioid angiomatosis and HIV infection. A neoplastic or infectious proliferative disease?]. AB - A case of "epithelioid angiomatosis" detected in a homosexual patient with positive seric HIV is presented. The skin lesions cytoplasm rich, closed y clumped together, with scanty stromal compound. Warthin-Starry staining [correction of tintions] did not show Bacillus causing "cat scratch disease". We review and analyse the features of this type of proliferation in patients infected with HIV. PMID- 2102738 TI - [Advances in the diagnosis of pulmonary complications in patients infected with the human immunodeficiency virus]. AB - Lung complications are the main cause of morbi-mortality in patients infected with HIV. In this review, we develop an algorithm with respect to the attitude to be taken when faced with an HIV-positive patient with respiratory affliction. The diagnosis value of non-invasive techniques are evaluated, as well as the right moment to be employed, and other future possibilities. Subsequently, the invasive studies are analysed (fiberoptic bronchoscopy, transbronchial biopsy, bronchial lavage samples). We dedicate a special section to bronchoalveolar lavage and to the test that must be carried out on the samples. Finally, the biological parameters which lead to the prognosis and/or control the treatment evolution of these patients are reviewed. PMID- 2102739 TI - [Internal medicine versus geriatrics. Antagonistic or complementary specialties]. PMID- 2102740 TI - [De Quervain's thyroiditis. A cause of fever of unknown origin]. PMID- 2102741 TI - [Osteoblastic lesions in histiocytosis X]. PMID- 2102742 TI - [Thoracic disk hernia. Apropos of a case]. PMID- 2102744 TI - [Heatstroke. A rapidly favorable evolution]. PMID- 2102743 TI - [Free intestinal perforation due to tuberculous enteritis]. PMID- 2102745 TI - [Leptomeningeal carcinomatosis as the primary manifestation of a gastric carcinoma]. PMID- 2102746 TI - [A psoas abscess secondary to appendicitis]. PMID- 2102747 TI - [The diagnosis of visceral leishmaniasis by gastric biopsy]. PMID- 2102748 TI - [Tuberculosis: present status]. PMID- 2102749 TI - [Main systems of classification and nomenclature of human immunodeficiency virus (HIV) infection]. PMID- 2102750 TI - [Comparison of chlorthalidone and sustained-action nifedipine in the treatment of mild to moderate arterial hypertension]. AB - The effectiveness and safety of sustained action nifedipine (NF) were compared to those of chlorthalidone (CL) in two groups of 35 and 37 patients with mild to moderate hypertension followed up for 4 months. There was a significant reduction in blood pressure (BP) after 15 days of therapy. The degree of control was acceptable with both drugs. A second drug was required in 20% patients of the NF group and in 30.8% of CL group. The therapeutic goal (BP less than 160/95) was achieved in 86.7% of patients in CL group and in 48.4% of those in NF group. We found 48.8% of dropouts in the NF group and none in CL group. There was a significant increase in blood glucose in CL group and a reduction of uric acid and an increase of HDL-cholesterol in NF group. Both drugs are useful to treat hypertension, although NF has the drawback of a high dropout rate and CL induces abnormalities in biochemical parameters. PMID- 2102751 TI - [Evaluation of the nutritional status in a population of Andalusian schoolchildren]. AB - The nutritional status of a population of school children was assessed with anthropometric data and information on nutrient intake. The three groups of subjects, all from the area around Velez Malaga (Malaga-Spain), were aged 6-7, 10 12 and 13-15 years. The data revealed no significant departures from normal anthropometric patterns with the exception of triceps skin fold thickness, which was lower for both sexes in all groups than the normal figure established for these groups in the spanish population. Although no serious imbalances were recorded in nutrient intake, fat intake was higher than the recommended levels for spanish children's, while carbohydrate, fiber, calcium, magnesium, iron and zinc intake was lower in all groups, and vit. B2 intake was lower in the 10-12 years old group. PMID- 2102752 TI - [Analysis of hospital morbidity as another tool in the diagnosis of health status]. AB - A descriptive analysis of hospital morbidity generated in our health center during one year was carried out. To this end, the official hospital registry books of the three reference hospitals of our area were used. Overall 1,114 hospital admissions were analyzed; most of them (59.3%) corresponded to young adults (25-44 years). The hospital frequentation rate was 85.8, and it was higher in the district with the lowest socioeconomic status. Mean hospital stay was 8.28 days (range 1 to 120 days). It was higher for individuals over 65 years, in males and in patients with respiratory diseases. The most common causes for admission in diagnostic groups were those related with pregnancy and delivery, followed by respiratory, gastrointestinal and genitourinary disorders. We conclude that the analysis of hospital morbidity is important as an indispensable complement of the diagnosis of the health status of the community, as it discloses several diseases which, despite their frequency and relevance, are often missed to be recorded in daily practice. PMID- 2102754 TI - [Scheduled consultation in primary care. Analysis of several relevant factors]. AB - We carried out a longitudinal prospective study of 5179 appointments with 1782 patients, which generated 4483 scheduled consultation in a 10-month period, so as to evaluate changes in compliance, duration of visit and month of appointment, depending on the age and sex of the patient and the cause for consultation. There were no sex or age group differences in compliance, but there were differences depending on the cause for consultation (p less than 0.0001). Obesity, dyslipemia and family planning were the groups with the lowest compliance. A time longer than 15 minutes for each visit was spent in a greater number of women than of men (p less than 0.0001). The age group with the longest time interval per visit was the 25-34 years group. There was also a difference depending on the cause for consultation, which was also not randomly distributed throughout the surveyed months (p less than 0.05). It was concluded that the compliance with appointments was directly related with the perceived morbidity, that subprograms of attention to women take a longer time per visit, and that the month of appointment determines the distribution of the causes for consultation. PMID- 2102753 TI - [Preliminary analysis in the implementation of a health program in child nutrition]. AB - In the view of the importance of nutrition for the eventual physical and psychological development of children, several ways to control the outcome of malnutrition, both due to excess and to defect, have been reported. Before introducing the adequate measures for the prevention and early diagnosis of malnutrition and obesity, the nutritional status of the children aged between 1-7 years was evaluated in the assigned population by means of the Shukla's index. In 681 evaluated children, 42 obese, 23 with malnutrition, 81 overweight and 105 with risk of malnutrition were detected. This prevalence of malnutrition and obesity warrants the implementation of screening measures for the nutritional status in children from the health center. A protocol to this end is outlined in the present article. PMID- 2102755 TI - [Determination of the degree of renal functioning and cardiovascular risk factors in an aged population seen at a health center]. AB - We report the results of a study to assess the glomerular filtration rate in the elderly population seen at the center and to investigate the prevalence of cardiovascular risk factors and use of drugs in this age group. The glomerular filtration rate could be measured in 64.6% of the elderly population. In 94 (17.6%) of the 825 evaluated individuals the clearance values were 50 ml/min or lower. Only 6 of them had previously known chronic renal failure. A high prevalence of concomitant cardiovascular risk factors was found (48.7% were hypertensive, 25.1% diabetic, 19% smokers, 24.1% had hyperlipidemia and 38.8% were obese). The rate of drug use was also high (69.6% took two or more drugs sustainedly). These findings indicate the need to evaluate the renal function in elderly people before prescribing drug therapy. PMID- 2102756 TI - [Community-acquired pneumonia: 573 cases]. AB - To evaluate the epidemiology and incidence of community-acquired pneumonia (CAP) a retrospective study of 573 cases which had been diagnosed during a 3 1/2 year period was carried out. There was a male predominance (2.09/1) with mean age of 53.33 years. The diagnostic delay (days) was 1.5. The mean hospital stay was 13.39 days. The most common underlying disease was COLD (27%). 34% of patients had received previous therapy. The most common clinical features were cough, fever, and mucous sputum. The most common radiological pattern was alveolar (81%). There was increased ESR and moderately high GOT and GPT. The microbiological diagnosis was achieved in 35.4%, with positive sputum culture (mostly pneumococcus) in 26.8% an positive blood culture in 5.9%. Ten patients died (1.7%). The following factors predicted a poor prognosis: age 75 years, underlying disease, bilateral radiological involvement and leukocytosis with neutrophilia. PMID- 2102757 TI - [Diabetic nephropathy]. PMID- 2102758 TI - [Bone pathology: diffuse and localized lesions]. PMID- 2102759 TI - [Helping the patients to changes their life styles: problems and perspectives of the primary care]. PMID- 2102760 TI - [Enrollment of the newborn in a healthy infant care program]. PMID- 2102761 TI - [Organization of hospital emergency services]. PMID- 2102762 TI - [Sporadic Gilbert's syndrome]. PMID- 2102763 TI - [Acquired toxoplasmosis]. PMID- 2102764 TI - [Sweet's syndrome. Apropos of a case]. PMID- 2102765 TI - [Ambulatory health care: an observation study]. PMID- 2102766 TI - [Role of laminar culture in the diagnosis of urinary infection]. PMID- 2102767 TI - The primary lesion theory of autoimmunity: a speculative hypothesis. AB - Autoaggression and autoimmune attack are established vernacular in the literature of autoimmune disease, and reflect the popular view that autoimmunity is a disease of immune dysregulation in which the immune system inappropriately attacks healthy tissues. The aim of this article is to focus attention on an alternative, indeed opposite, view--that autoimmunity represents the response to a primary lesion in the target tissue, rather than its cause, and that like alloimmunity, autoimmunity is physiological appropriate and protective. The cell death and tissue damage which results is characteristic of an immune response programmed to eliminate immunogen, remove detritus and isolate the lesion. PMID- 2102768 TI - Enhanced inflammatory reactivity in the pathogenesis of spondyloarthropathies. AB - Pathogenesis of seronegative spondyloarthropathies such as ankylosing spondylitis and reactive arthritis is not known. Growing evidence indicates that microbial structures such as Chlamydia antigen and Yersinia antigen are present in the inflamed joints of patients with reactive arthritis. Microbial antigens can activate the host's inflammatory mechanisms. After the activation, the course of inflammation can be postulated to be affected by the host factors responsible for amplification of the inflammatory reaction and elimination of the foreign structures. Thus, the amplification, whether strong, moderate, or weak, may contribute to the degree of inflammatory tissue injury in patients with seronegative spondyloarthropathies. This review will discuss the role of increased inflammatory reactivity in the pathogenesis of HLA-B27 associated spondyloarthropathies, with special reference to reactive arthritis triggered by yersinia enteritis. PMID- 2102769 TI - Secretor status and infection in patients with Graves' disease. AB - We have demonstrated that the inability to secrete the water soluble glycoprotein form of the ABO blood group antigens into saliva is significantly more common in patients with Graves' disease than control subjects (40% vs 27%: P less than 0.025) but not among those with Hashimoto's thyroiditis or spontaneous primary atrophic hypothyroidism. Non-secretion is associated with increased susceptibility to infection and to asymptomatic carriage of some microorganisms. Although Yersinia enterocolitica has been found to express antigen cross reactive with the TSH receptor, we did not find an increased prevalence of Yersinia species in the faeces of 107 patients with Graves' disease. The isolation rate (less than 1%) was similar to that observed in the local population with diarrhoeal illness. Salivary IgA levels determined by whole cell ELISA with Y. enterocolitica 03 were not elevated in the majority of specimens examined. The results suggest that in contrast to reports from Scandinavia, there is no strong evidence that yersiniae play a role in the pathogenesis of Graves' disease among patients in South east Scotland. Non-secretors are significantly over represented among patients with several other autoimmune diseases; however, with the exception of antitubulin antibodies, non-secretors with Graves' disease did not have more antibodies to other human antigens than secretor patients. PMID- 2102770 TI - Yersinia enterocolitica and thyroid autoimmunity. AB - The concordance rate of Graves' disease in pairs of identical twins of 30 to 60% points to the influence of environmental factors, and infections have often been incriminated in the pathogenesis. More than 15 years ago we demonstrated an increased frequency of antibodies to Yersinia enterocolitica (Y. ent.) serotype 3, which later was confirmed by others, suggesting a link between infection with Y. ent. and autoimmune thyroid diseases. PMID- 2102771 TI - Autoimmune thyroid diseases and enteropathogenic Yersinia enterocolitica. PMID- 2102772 TI - Antibody activity against lipopolysaccharides, lipid A and proteins from Enterobacteriaceae in patients with chronic inflammatory liver diseases. AB - These studies are concerned with detection of circulating antibodies against various defined enterobacterial antigens in patients with chronic inflammatory liver diseases such as chronic hepatitis type B (n = 46), chronic active hepatitis (CAH) of autoimmune type (n = 10), alcoholic cirrhosis (n = 24) and primary biliary cirrhosis (PBC) (n = 24) as well as in healthy individuals (n = 39). Anti-LPS and anti-lipid A were determined by hemolytic and hemagglutination assay. Immunoblot technique was used to investigate the antibody activity against plasmid encoded proteins from Yersinia enterocolitica. Persistent titers of anti LPS up to serum dilution 1:32.768 were found with hemolytic and hemagglutination assay in patients with alcoholic cirrhosis or PBC and in healthy control. In contrast nearly 50% of patients with chronic hepatitis B had no hemolytic antibodies against the two LPS E. coli serotypes at the time of liver biopsy. Anti-lipid A was detectable in 58% of patients with alcoholic cirrhosis but in low titers in less than 10% in the other groups (p less than 0.001). Alcoholic cirrhosis was also associated with a high frequency of IgG and IgA antibodies against plasmid encoded proteins from Yersinia enterocolitica. The data indicate that the O-polysaccharides as strong antigens are physiologically exposed to the immune system while lipid A and enterobacterial proteins are solely immunogenic under abnormal conditions. PMID- 2102773 TI - Myoplasmic phosphate metabolites in the integration of oxidative phosphorylation and contractile function in the myocardium. AB - The role of cytosolic concentrations of ADP, ATP, phosphocreatine, and Pi in the regulation of energy turnover in the myocardium has been investigated. For this purpose pool sizes of cytosolic adenine nucleotides or total creatine were significantly reduced, and creatine kinase activity completely inhibited. The findings show that the cytosolic ADP, the [ATP]/[ADP] ratio, and the phosphorylation potential are not uniformly related to the intensity of contractile function and the oxidative phosphorylation rate. Other mechanisms of coordination of these processes have to be taken into account. PMID- 2102774 TI - Molecular bases for the construction of artificial immunogens. AB - The molecular and cellular mechanisms of action of synthetic polyions on immunogenesis are reviewed. The results of studies of the principal properties of polyionic immunostimulators and of the cell responses to the action of these stimulants have been used to construct artificial antigen-polyion complexes with enhanced immunogenic properties. The vaccinating properties of such macromolecular complexes, constructed with the use of bacterial or viral antigens, are analysed. PMID- 2102775 TI - Elongation factors Tu and G change their conformation on interaction with ribosomes. AB - Limited trypsinolysis was used to study conformational changes in elongation factors Tu and G. The trypsin cleavage rates of the factors differed and depended on both their interaction with ligands and the presence or absence of ribosomes. When the factors were bound to ribosomes, changes in their sensitivity to trypsin were observed depending on whether GDP or GTP was present in the complex, i.e. on the hydrolysis state of the guanine nucleotide ligand. The possible significance of factor structural changes for their functioning is discussed. PMID- 2102776 TI - Bone marrow and intrathymic precursors of T-cells produce a factor which enhances colony formation in the spleen. AB - Bone marrow Ig-Thy-1-SC-1- stem cells (precursors of T-lymphocytes, PTL, containing the SC-1 antigen) spontaneously secrete a humoral factor. When bone marrow Ig-Thy-1-SC-1- cells were treated with this factor they became able to form haemopoietic colonies in the spleens of lethally irradiated mice. This new colony-stimulating factor (CSF) is thermostable and has a molecular mass of about 25-30 kDa. Production of the CSF by bone marrow SC-1+Thy-1- cells was stimulated by treatment with the thymus preparation Thymoptin. Such treatment of bone marrow SC-1+Thy-1- cells also induced the production of a suppressor factor (thermolabile, molecular mass about 45 kDa), that reversed the effect of the CSF. The CSF and the suppressor factor are both also produced by cortisone-resistant radioresistant L3T4-Lyt-2-SC-1+ thymocytes (i.e. intrathymic PTL). The regulation of haemopoiesis appears to be a normal function of bone marrow PTL. PMID- 2102777 TI - Participation by opioids in the immunostimulatory activity of myelopeptides. AB - Bone marrow myelopeptides (MP), besides having immunostimulatory activity, had a pronounced dose-dependent effect on the development of pain sensitivity in mice. Nanogram amounts of MP evoked a hyperalgesic response and increased antibody formation to sheep red blood cells three to nine times. Milligram amounts of MP had a hypoalgesic effect and did not affect antibody response. Opioid peptides derived from the bone marrow MP are involved in the expression of the antibody response, and a mixture of synthetic opioids, corresponding in composition to that found in natural MP, stimulated antibody production. The antibody stimulating effect of MP was abolished by naloxone. Of the opioid peptides, only beta-endorphin showed antibody-stimulating activity. On reversed-phase chromatography the antibody-stimulating peptides and beta-endorphin were eluted in different fractions, indicating that the immunostimulatory and opioid activities are produced by different peptide molecules. PMID- 2102778 TI - Modelling of type 1 diabetes with monoclonal antibody ICA-1. AB - In order to investigate the possible role of pancreatic beta-cell p(64-69) antigens in the development of diabetes type 1, a monoclonal antibody (ICA-1) to the 64-69 kDa antigen family was produced and characterized. Short-term (0.25 mg per rat, intraperitoneally, daily for 9 days) and prolonged (0.125 mg per rat, intraperitoneally, three times a week for 8 weeks) administration of ICA-1 to Wistar rats caused the development of a diabetes-like reaction characterized by moderate hyperglycaemia, markedly reduced pancreatic insulin content, and depressed insulin secretion. After 9 days, histological changes in the pancreas indicative of early insulitis were also observed. Continued ICA-1 treatment increased mononuclear infiltration of the islets and progressive beta-cell damage became evident. In order to confirm the insulin-dependent character of this early stage diabetes induced by ICA-1, rats were injected with insulin in liposomes, whereupon normalization of serum insulin levels was observed together with a decrease in mononuclear infiltration. These results indicate that the 64-69 kDa antigen family is closely related to the hypothetical primary target protein that may play a role in the development of autoimmune beta-cell destruction. PMID- 2102779 TI - Muramylpeptides augment expression of Ia-antigens on mouse macrophages. AB - The muramylpeptide N-acetylglucosaminyl-beta 1----4-N-acetylmuramyl-L-alanyl-D isoglutamine (GMDP) was shown by flow cytometry to produce a dose-dependent increase in the expression of Ia-antigens by mouse peritoneal macrophages in vitro. Muramyldipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) had a similar, but weaker, effect. GMDP also induced expression of Ia-antigens by murine peritoneal macrophages in vivo. GMDP acted directly on the macrophages because Ia-antigen expression by cells of the cloned mouse myelomonocytic line WEHI-3 was also induced. Expression of the interleukin-2 receptor on the surface of the macrophages was also stimulated by GMDP, indicating that GMDP may influence development of the immune response through this mechanism. PMID- 2102780 TI - The effect of inhibitors of transcription and translation on basal and haem induced tryptophan-2,3-dioxygenase activity in the rat liver. AB - The effect of actinomycin D and cycloheximide on basal tryptophan-2,3-dioxygenase (EC 1.13.11.11) activity in Wistar rat liver and on the enzyme activity induced by pretreatment with haemin was studied. Inhibition of either transcription or translation was accompanied by a reduction in tryptophan oxygenase activity, and this occurred more rapidly in the case of inhibition of translation. A 40% and 45% reduction in holoenzyme activity was found 2.5 and 6.5 h after introduction of cycloheximide and actinomycin D, respectively. Pretreatment with the antibiotics did not impair saturation of the apoenzyme by exogenous haem but haem induced tryptophan oxygenase activity was affected in various ways. Introduction of cycloheximide after haemin was accompanied by a rapid fall in the activity of both forms of the enzyme, but when transcription was inhibited under these conditions there was a subsequent increase in both holoenzyme activity and overall tryptophan oxygenase activity. The results support the concept that a regulatory pool of haem exists in hepatocytes and that haem is involved in both the activation and the degradation of tryptophan oxygenase. PMID- 2102781 TI - Immunochemical analysis of adrenocortical cytochrome P450scc: 1. Monoclonal antibodies against haemprotein. AB - Twelve stable mouse hybridoma cell lines producing monoclonal antibodies against bovine adrenocortical cytochrome P450scc were prepared. All the monoclonal antibodies interacted specifically with the antigen as shown by radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), dot-immunoblotting, and Western blot analysis, but did not precipitate in Ouchterlony double-immunodiffusion analysis. A highly sensitive competitive RIA based on monoclonal and polyclonal mouse antibodies was developed to determine the total content of P450scc in adrenocortical mitochondria. Three of the monoclonal antibodies strongly inhibited the conversion of cholesterol to pregnenolone. PMID- 2102782 TI - Effect of prolactin on phosphatidylcholine hydrolysis via phospholipase C in isolated adrenocortical cells of guinea pig. AB - Prolactin significantly increased the rate of incorporation of [3H]choline into phosphorylcholine (PRC) in a purified suspension of guinea pig adrenocortical cells. The rate of phosphatidylcholine (PTC) labelling and cellular PTC content did not change. In cells prelabelled with [3H]choline or CDP [14C]choline, prolactin diminished the rate of reduction of the radioactive PRC pool after 60 90 min incubation without any change in the rate of PTC biosynthesis. Taken together, these findings suggest that prolactin stimulates the hydrolysis of PTC by phospholipase C into PRC and diacylglycerol. The significance of this effect as part of the mechanism of action of prolactin on adrenocortical cells is discussed. PMID- 2102783 TI - The effect of neonatal castration of male rats on the level of sex-hormone receptors in the hypothalamus and hypophysis of adult animals. AB - The concentration of oestradiol (E2) and testosterone (T) cytosolic and nuclear receptors was studied in the pituitary and hypothalamus of adult male rats gonadectomized either on the first day after birth (long-term castrates) or in adulthood (short-term castrates). Intact male rats and short-term castrates had the same levels as each other of cytosolic and nuclear oestrogen and androgen receptors in the pituitary, mediobasal hypothalamus (MBH), and preoptic anterior hypothalamus (POAH). In neonatally castrated males the number of nuclear T binding sites in the pituitary and both areas of the hypothalamus decreased, whereas the number of nuclear E2-receptors was reduced only in the MBH. The number of E2-receptors in the POAH of such animals increased. The number of E2- and T-binding sites in the nuclear fraction of the MBH and POAH was the same in long-term castrates whether they did not receive testosterone propionate (TP) or received it from 7 days after birth until sexual maturity. Conversely, the T receptor concentration in the hypophysis of neonatally castrated males who received TP was higher than in such animals which did not, but still lower than the level in intact adult rats; the number of hypophyseal nuclear E2-binding sites in long-term castrates which received TP was 1.5 times higher than in all the other groups of animals. The data demonstrate that in male rats sex-hormone receptors are involved in the sexual differentiation of the brain. PMID- 2102784 TI - Experimental evidence for hypothalamic paraventricular nucleus involvement in the regulation of carbohydrate homeostasis. AB - An attempt was made to elucidate whether the hypothalamic paraventricular nucleus (PVN) is involved in carbohydrate homeostasis regulation in rats. The cellular responses to various disturbances of homeostasis were studied in the neuronal subdivisions (subnuclei) of the PVN. The responses were assessed in terms of changes in the sizes of the cell nuclei, nucleoli, and cytoplasm, and by the ultrastructural changes evident in cellular organelles. Significant cellular responses were observed in several subnuclei, with the nature of the responses being determined by the type of homeostatic alteration. The results indicate the possible involvement of the PVN subnuclei in the regulation of carbohydrate homeostasis. PMID- 2102785 TI - Long-term serial cultivation of human vascular endothelial cells. AB - Long-term mass culture of human large vessel endothelial cells (EC) from aorta, umbilical cord vein, and pulmonary artery was undertaken and the cells characterized. The cells possessed all the major features of EC, proliferated rapidly [population doubling (PD) time 17-42 hours] and survived 40-60 PD. The cells were cultured under different conditions, and the following combination chosen as optimal for routine culturing: Medium 199, supplemented with 20% human serum, 4 mM glutamine, 200 micrograms ml-1 EC growth factor from human brain, 100 micrograms ml-1 heparin. The cells were grown on gelatin-coated or fibronectin coated substrate. The results of the experiments with large vessel EC cultivation were used to develop a system for the culture of capillary EC from human lung and kidney. Mass-scale culture of large vessel and capillary EC is valuable in the investigation of EC function and for clinical purposes. PMID- 2102786 TI - Idiopathic chronic disseminated intravascular coagulation. AB - Disseminated intravascular coagulation, whether acute or chronic is usually associated with an underlying causative condition. In this case chronic disseminated intravascular coagulation persisted in one 79 year old man for 3 years with no detectable underlying cause. PMID- 2102787 TI - Thrombogenicity of a factor IX concentrate quantitated in a canine model. AB - Dose-ranging studies with a batch of factor IX concentrate have been performed in a canine non-stasis model of thrombogenicity. Doses between 50 and 200 IU/kg were infused over a 30 min period, and beagles were found to be more sensitive than greyhounds with regard to subsequent alterations in haemostatic parameters over a 150 min period. In beagles we detected significant increases in plasma fibrin(ogen) degradation products and reduction in fibrinogen concentrations in a dose-related manner after infusion of factor IX concentrate over the range 50-150 IU/kg. Plasma fibrinopeptide A was the most sensitive marker of activation of coagulation with significantly increased levels after factor IX at 50 IU/kg compared with control infusions of albumin. Recovery of infused factor IX was similar to values reported in man. In these experiments, measurement of urinary fibrinopeptide A did not prove to be a useful indicator of thrombogenicity. In conclusion, the beagle non-stasis model will provide a sensitive method to quantify the unwanted thrombogenic activities associated with the use of high doses of certain factor IX concentrates. PMID- 2102788 TI - The influence of pH on aggregation of human washed platelets induced by thrombin or collagen. AB - The anti-aggregating activity of L-arginine and its analogues has been investigated in washed human platelets. The ability of these compounds to inhibit platelet aggregation induced by thrombin or collagen was mimicked by a change in the external pH of the buffer from pH 8.0 to pH 7.4. Of the several analogues tested, only benzoyl-L-arginine ethylester (BAEE) inhibited thrombin- but not collagen-induced platelet aggregation. In platelet-rich plasma, BAEE also inhibited platelet aggregation without inhibiting fibrin clot formation. These results suggest that the marked sensitivity of washed human platelets to small changes in the external pH may lead to misinterpretation of the anti-aggregatory potency of protonated test drugs. For work with human washed platelets a physiological salt solution with more buffering capacity than Krebs-bicarbonate (such as Tyrode-HEPES) is recommended. PMID- 2102789 TI - Anticardiolipin antibodies in HIV-negative and HIV-positive haemophiliacs. AB - Anticardiolipin antibodies (ACA) were determined in 72 heavily transfused haemophiliacs, 43 HIV-positive and 29 HIV-negative. The presence of ACA was detected in 10 patients, all of them infected by HIV: 8 in CDC II, 1 in CDC III and 1 in CDC IV. The comparison with alterations of other laboratory markers in HIV-infected patients did not show any statistically significant difference between ACA-negative and -positive patients. In summary, ACA were found only in HIV-infected haemophiliacs. In this subgroup of patients the presence of ACA was not associated with progression to AIDS. PMID- 2102790 TI - Clotting factors in tumour tissue: implications for cancer therapy. AB - Considerable progress has been made recently in understanding the mechanisms and significance of coagulation activation in human malignancy. Neoplastic cells may activate coagulation reactions directly, that is through contact with coagulation factors; or indirectly by formation of cytokines capable of activating certain host cells such as macrophages or endothelial cells. Data suggest that at least two autoregulatory pathways involving components of coagulation and fibrinolysis pathways exist. In one of these, tumour cell procoagulants lead to generation of thrombin in the tumour periphery. Thrombin is a mitogen that may also contribute to tumour stoma formation. Alternatively, tumour cells may express urokinase responsible for generation of cell surface-related proteolysis that may facilitate tumour cell proliferation, invasion and metastasis. An appreciation of these diverse mechanisms may permit rational design of clinical trials of agents capable of interrupting relevant pathways. PMID- 2102791 TI - Monoclonal antibody-based plasma assays for fibrin(ogen) and derivatives, and their clinical relevance. AB - The haemostatic balance can basically be described as the equilibrium between fibrin formation (coagulation) and fibrin lysis (fibrinolysis). The status of this balance may therefore be reflected by the products of these two processes. Until recently, the tests for assessment of fibrin(ogen) degradation products were performed in serum since they were based on polyclonal antibodies, which cross-react with fibrinogen. However, the use of serum introduces many artefacts so the utility of these serum tests is limited. New assays have now become available, which can be divided into quantitative enzyme immunoassays (EIAs) and semi-quantitative latex agglutination assays. The new assays can be carried out in plasma since they use highly specific monoclonal antibodies, the majority of which do not cross-react with fibrinogen. This makes it possible to avoid the serum artefacts. Furthermore, these plasma assays can discriminate between degradation products of fibrin and those of fibrinogen (FbDPs and FgDPs, respectively). The possible clinical utility of the new assays is discussed on the basis of literature data on the following clinical states: deep venous thrombosis (DVT) and pulmonary embolism, liver disease and liver transplantation, sickle cell disease, renal diseases, pregnancy and preeclampsia, disseminated intravascular coagulation (DIC), malignancy, coronary artery disease and thrombolytic therapy. Fibrinolysis appears to be accompanied by fibrinogenolysis. Detection of fibrin(ogen) derivatives may be used to rule out DVT and to monitor efficacy of anticoagulant treatment for DVT or DIC, and reflects severity of renal disease but not renal function. High levels of FgDPs were found during orthotopic liver transplantation and thrombolytic therapy. Fibrin(ogen) degradation products cannot be used to predict reperfusion following thrombolytic therapy. The fibrinolytic system remained active during normal and complicated pregnancy and in patients with malignancies. The new assays provide valuable information on fibrin(ogen)olysis in several diseases. More information on the haemostatic balance may be obtained by using these new assays for fibrin(ogen)olysis products in combination with assays for coagulation products. PMID- 2102792 TI - The mechanism of extertional fatigue in heart failure. AB - The mechanism of exertional fatigue in heart failure appears to be considerably more complex than was originally thought. Although it still seems likely that muscle underperfusion is the major culprit, the possibility that skeletal muscle changes contribute to the fatigue suggests that several new therapeutic modalities may improve exercise capacity in heart failure. If muscle atrophy due to de-conditioning or malnutrition is found to contribute to fatigue, exercise capacity in heart failure could be improved, at least in part, by exercise training or nutritional supplementation. Alternatively, agents such as anabolic steroids or growth hormone could be used to stimulate muscle hypertrophy and, thereby, help to improve the fatigue. Heart failure is a common disorder, affecting over three million Americans and many more people throughout the world. One of the most disabling problems experienced by these patients is exertional fatigue. Patients report that they are easily fatigued during normal daily activity. During maximal exercise testing, patients usually terminate exercise early due to fatigue of the legs associated with an early increase in the concentration of lactate in the blood. Traditionally, such exertional fatigue has been attributed to skeletal muscle underperfusion. Over the past five years, however, there has been increasing evidence that heart failure is associated with intrinsic skeletal muscle changes which may also contribute to the exertional fatigue. Nuclear magnetic resonance studies using 31P have demonstrated abnormal skeletal muscle metabolic responses to exercise that do not appear to be due to muscle under-perfusion. Skeletal muscle biopsy studies have demonstrated a variety of changes in patients. Anthropometric studies suggest that a generalized loss of muscle mass may occur in heart failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102793 TI - Mechanism of death in patients with congestive cardiac failure: the change in plasma norepinephrine and its relation to sudden death. AB - It has previously been observed that patients with congestive cardiac failure who die with progressive pump dysfunction tend to have higher levels of plasma norepinephrine than do patients who die suddenly and unexpectedly. However, it may be difficult to distinguish death with pump failure from sudden death. We have analyzed retrospectively 10 patients with congestive cardiac failure who clearly died suddenly and unexpectedly, and have compared them with 10 patients who clearly died of progressive pump dysfunction. Each patient had at least two sequential measurements of plasma norepinephrine before death. Patients dying of progressive pump failure tended to have a progressive rise in plasma norepinephrine from 475 to 1119 pg/ml (P less than 0.004) over an average period of 39 months. Patients dying suddenly and unexpectedly, on the other hand, had a non-significant decrease in plasma norepinephrine from 485 to 407 pg/ml over an average period of 26 months. The data suggest that an increase in plasma norepinephrine may be a marker for death from progressive pump dysfunction. This hypothesis may now be tested in two large multicenter trials where plasma norepinephrine is being monitored over time. The concept that changes in plasma norepinephrine can predict the type of death in patients with congestive cardiac failure may, if valid, be useful in clinical practice. PMID- 2102794 TI - Modulation of myothermal economy of isometric force generation by positive inotropic interventions in the guinea pig myocardium. AB - Isometric force development has been measured simultaneously with liberated heat in papillary muscles from the right ventricle of the guinea pig, using rapid antimony-bismuth thermopiles. The following components of the contractile cycle and their relation to energy consumption were evaluated: (1) basal metabolism; (2) crossbridge cycling; (3) calcium cycling; and (4) recovery processes. The influences of isoproterenol, high calcium and UDCG-115, a calcium-sensitizing substance, on these four energy compartments of the muscle were studied relative to their positive inotropic effects. Isoproterenol increased initial heat per peak developed tension or per tension-time integral from 7.4 +/- 1.55 to 11.65 +/ 1.15 mucal/g cm (p less than 0.02) or from 4.52 +/- 0.79 to 8.14 +/- 0.77 mucal/g cm sec (p less than 0.01), respectively. In contrast, these ratios were unchanged from control values by positive inotropic interventions with 11 mM calcium or UDCG-115. The increase of initial heat for a unit of mechanical activity due to isoproterenol is attributable to activation and contractile protein processes, i.e. the activation heat increased from 0.24 +/- 0.05 to 0.68 +/- 0.13 mcal/g (p less than 0.01) and tension-dependent heat per tension-time integral increased from 2.24 +/- 0.60 to 5.18 +/- 0.89 mucal/g cm sec (p less than 0.01). We conclude that isoproterenol increases the number of calcium ions released into the sarcoplasm during each activation cycle. It also alters the rate of crossbridge cycling associated with a decreased economy of force generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102795 TI - Effects of acute hypoxia on the normal and diseased sinus node. AB - We have studied the effects of breathing 12% oxygen in three groups of patients with sinus bradycardia: 11 with intrinsic sick sinus syndrome, 11 with extrinsic sick sinus syndrome and 11 without any evidence of sinus dysfunction. During hypoxia, the heart rate increased by an average of 6.7 beats/min in the patients with intrinsic sick sinus syndrome, 15.7 beats/min in the patients with extrinsic sick sinus syndrome and 14.3 beats/min in those with normal sinus node function. The difference in response of the heart rate between the two groups with sick sinus syndrome was highly significant (P less than 0.001). There was no difference between the three groups in the response of the blood pressure, ventilation, and partial pressures of oxygen and carbon dioxide. The increased heart rate which accompanies hypoxia is thought to be mediated through sympathetic mechanisms consequent on hyperventilation. In the intrinsic sick sinus syndrome, there is evidence that the sympathetic tone is already increased and this may limit the extent of the tachycardia due to hypoxia. Hypoxia may be a useful clinical test to distinguish between the two forms of sick sinus syndrome. PMID- 2102796 TI - Species dependence of contraction velocity in single isolated cardiac myocytes. AB - Single myocytes were isolated from mouse, rat, guinea-pig, rabbit, sheep and human ventricle, and the amplitude and velocity of their unloaded contraction measured using a video camera and a system for measuring their length. Measurements were done at 32 degrees C in solutions containing either low calcium (1-1.3mM) or a concentration of calcium (usually 8mM) that produced a maximum amplitude of contraction. Unlike the cells of the majority of species, human cells could be successfully isolated only by using protease in addition to collagenase. To determine the effect of protease, guinea-pig cells were prepared with or without this enzyme. There was no significant difference in the characteristics of the cells prepared by either method. There was little species variation in the length of the cells or the length of resting sarcomeres. However, there were considerable species differences in the velocity of shortening and of relaxation. Myocytes from larger animals tended to contract and relax more slowly than those from smaller animals, although there was little systematic variation in the absolute amplitude of contraction. There was a significant correlation between the normalised contraction velocity of single cells and the average heart rate reported for that species. The trend for decreased relaxation velocity with lower heart rate did not reach statistical significance. Right ventricular cells from rat heart contracted more rapidly than those from the left ventricle, a finding similar to that reported for intact muscle strips. We conclude that species and left/right differences observed in the contraction velocity of whole muscle can be detected at the level of the single myocyte. PMID- 2102797 TI - Hormonal response in untreated myocardial infarction. AB - Plasma levels of a variety of hormones have been measured in patients within two hours of the onset of symptoms of myocardial infarction and before commencement of any treatment. Increased plasma concentrations were found for norepinephrine, epinephrine, glucagon, aldosterone, vasopressin, atrial natriuretic peptide, corticotrophin, prolactin, cortisol and substance P while plasma renin activity was raised. The plasma concentrations of insulin, growth hormone, neurotensin, bombesin and vasointestinal peptide were normal. PMID- 2102798 TI - Calcium antagonists and the "stunned" myocardium. AB - Hearts which are made ischemic for relatively short periods of time, and then re perfused, exhibit a temporary decline in tension-generating activity but are not irreversibly injured". Experiments were undertaken to find out whether such "stunned" hearts develop a perfusion defect, and whether chemically heterogeneous Ca(2+)-antagonists provide protection, when used prophylatically. "Stunning" was produced by repetitive 10 minute episodes of ischemia, followed by 15 minutes of reperfusion. The experimental model was the Langendorff-perfused rat heart, and the perfusion buffer was Krebs-Henseleit solution at 37 degrees C. To detect perfusion defects, fuchsin dye was added to the buffer. No evidence of a perfusion defect was obtained. Nevertheless, 10(-8)M nifedipine. 10(-8)M verapamil, 10(-8)M felodipine, and 10(-7)M diltiazem all conferred protection, as gauged by recovery of function after three successive 10 minute episodes of ischemia. PMID- 2102799 TI - Alterations of calcium metabolism in spontaneously hypertensive rats. AB - We have examined the femurs of eight male spontaneously hypertensive rats and eight male Wistar Kyoto rats, aged 24 weeks. The mineral density of the bones was determined at the mid-point of the femurs by dual photon absorptiometry and the calcium content was estimated on bone ash by atomic absorption spectrophotometry. The data show that spontaneously hypertensive rats have lower bone density and calcium content than do age-matched Wistar Kyoto rats. PMID- 2102800 TI - Potassium exchange in the human heart: effect of heart rate and myocardial ischemia. AB - The concentration of potassium ions, [K+], in the blood of the coronary sinus was recorded using catheter-tip potassium ion-selective electrodes during fixed rate atrial pacing for up to six minutes in five patients with normal hearts (control group) and in eight with coronary artery disease. Four patients with coronary artery disease developed pain in the chest and changes on the electrocardiogram during atrial pacing (ischemic group). In the control group, the coronary sinus [K+] began to rise after three seconds to a peak increase of 0.33 +/- 0.04 mmol.l 1 (p less than 0.001) and then returned to the resting value. On cessation of pacing, coronary sinus [K+] fell rapidly and transiently below the resting value. In the ischemic group, the coronary sinus [K+] began to rise after three seconds to a peak of 0.42 +/- 0.05 mmol.l-1 (p less than 0.01); it remained elevated throughout the period of atrial pacing (p less than 0.01) and fell rapidly and transiently below the resting value on cessation of pacing. Four patients with coronary artery disease did not develop ST segment depression during atrial pacing; in two the changes in coronary sinus [K+] were the same as those in the ischemic group, and in two they were similar to those in the control group. These data show that in man there is an immediate and transient loss of potassium from the myocardial cells when the heart rate is increased and that this loss is restored the heart rate returns to the resting rate. Myocardial ischemia causes a continuing efflux of potassium from myocardial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102801 TI - Species differences in susceptibility to ischemic injury and responsiveness to myocardial protection. AB - Isolated hearts from rabbits, hamsters, ferrets, gerbils, rats, mice and guinea pigs were used to investigate species differences in (i) stability during aerobic perfusion, (ii) susceptibility to ischemic injury and (iii) responsiveness to cardioplegic protection. During 120 minutes of continuous aerobic perfusion, the rate of functional deterioration differed between species. The rabbit was the most stable and the guinea pig the least: the mean +/- SEM of the left ventricular developed pressure falling, after 120 minutes of perfusion, to 82 +/- 4% and 60 +/- 6%, respectively. In studies with 30 minutes of ischemia and 60 minutes of reperfusion, the developed pressure recovered to 72 +/- 2, 71 +/- 2, 65 +/- 3, 64 +/- 2, 58 +/- 3, 50 +/- 8 and 50 +/- 2% of its pre-ischemic value in the rabbit, hamster, ferret, gerbil, rat, mouse and guinea pig, respectively. With 60 minutes of ischemia, the recovery of developed pressure in the guinea pig, rabbit, rat, mouse, hamster, ferret and gerbil was 5 +/- 1, 19 +/- 2, 22 +/- 3, 30 +/- 5, 55 +/- 4, 60 +/- 2 and 45 +/- 5%, respectively. Creatine kinase leakage and changes in tissue metabolite content generally reflected the degree of functional injury. In further studies, groups of 6 hearts were infused for 2 minutes with St. Thomas' Hospital Cardioplegic Solution, then subjected to 30 minutes of ischemia. Cardioplegia improved the recovery of developed pressure in the rabbit, hamster, gerbil, rat and mouse (from 72 +/- 2, 71 +/- 2, 64 +/- 2, 58 +/- 3 and 50 +/- 8% to 82 +/- 3, 103 +/- 3, 84 +/- 4, 77 +/- 2 and 78 +/- 5%, respectively; p less than 0.05 for each species). However, no protection was observed in the ferret and guinea pig (65 +/- 3 and 50 +/- 2% versus 66 +/- 3 and 47 +/- 6%, respectively; p = NS). With cardioplegia, tissue high-energy phosphates increased significantly in all species except the gerbil. Rat and guinea pig hearts were taken for time-response studies (ischemia for 15, 20, 30, 45, 50 and 60 minutes in the rat and 15, 30, 45 and 60 minutes in the guinea pig) with or without cardioplegia. In the rat, cardioplegia improved recovery over an ischemic time-window of 20-45 minutes, but in the guinea pig no improvement was detected. Creatine kinase leakage reflected the patterns of functional recovery. In contrast, high-energy phosphates were preserved better in both species after 30 minutes of ischemia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2102802 TI - Effects of administration of L-propionylcarnitine during ischemia on the recovery of myocardial function in the anesthetised pig. AB - The effects of L-propionylcarnitine (50 mg/kg) were studied in open-chest anesthetized pigs in which the blood flow in the left anterior descending coronary artery was reduced to 20% of baseline. A group of 7 animals given L propionylcarnitine after 30 minutes of ischemia was compared with a group of 8 animals treated only with saline. After 60 minutes of ischemia the myocardium was reperfused for 2 hours. In both groups, the reduction of coronary artery blood flow abolished contraction of the affected myocardium and caused similar decreases in mean arterial blood pressure, the maximal rate of rise in left ventricular pressure, cardiac output, and ATP level and energy charge of the affected zone. L-propionylcarnitine did not affect any of these changes. Two hours of reperfusion caused further deterioration of systemic hemodynamics in both groups, although the decreases in cardiac output (P greater than 0.05) and mean arterial blood pressure (P less than 0.05) were smaller in the animals treated with L-propionylcarnitine. Left ventricular work, which decreased similarly in both groups during ischemia, deteriorated further in the saline treated group during reperfusion. This decrease was significantly attenuated by L propionylcarnitine. Two hours of reperfusion resulted in only a partial return of blood flow to the reperfused ischemic myocardium, amounting to 53% of baseline in the saline-treated and to 72% of baseline in the L-propionylcarnitine-treated animals. The energy charge increased in both groups, but the increment tended to be less (P greater than 0.05) in the animals which had received L propionylcarnitine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102803 TI - Current research views on myocardial reperfusion and reperfusion injury. AB - This article discusses the types of reperfusion injury, some of the causes of the injury and the possible role of the radical scavengers in protecting against it. The methodological problems that have plagued this field are explored and some answers put forward, although we are sure that further questions will have been raised. There are now reasons to question the use of the tetrazolium staining procedure which has become the "gold standard" for measurements of infarct size. It seems likely that it is adequate only as a screening procedure, and even then will be associated with a troublesome number of false positives. Collateral flow is an important determinant of infarct size and simultaneous measurements of collateral flow are essential in the interpretation of the effects of drugs on infarct size. The limitations of the various animal models are important when relating experimental findings to the clinical condition. After a decade of research, reperfusion injury is itself still under question, and there remains confusion as to the role that oxygen-derived free radicals may play in the ischemic/reperfused myocardium. However, we believe that, from the experimental data available, oxygen derived free radicals are involved in the overall pathophysiology of ischemia and reperfusion, although the full extent remains to be clarified and the therapeutic implications explored. PMID- 2102804 TI - Arrhythmogenic age-related effects of lysophosphatidylcholine in the rat heart. AB - Ventricular arrhythmias are the most common cause of death among patients with coronary artery disease; this is more evident in the elderly, who tend to have more severe coronary artery disease and age-dependent modifications of cardiac electrophysiology. Lysophosphoglycerides, which accumulate in the ischemic myocardium, are responsible for oscillatory after-potentials and may contribute to the development of ventricular arrhythmias. The aim of this study was to examine the effects of lysophosphatidylcholine (5 x 10(-5) M) in the absence or presence of epinephrine (10(-6) M) in isolated, perfused hearts from adult (6-12 months old) and senescent (24 months old) rats. Rat hearts (30/group) were randomly divided into four groups each of which included hearts of 6, 12 and 24 month old rats. The groups comprised a control group, a group treated with epinephrine, a group treated with lysophosphatidylcholine and a group treated with both epinephrine and lysophosphatidylcholine. Analysis of arrhythmias indicated a linear correlation between epinephrine- and lysophosphatidylcholine induced ventricular arrhythmias and age. The incidence of arrhythmias was higher in the hearts treated with epinephrine and lysophosphatidylcholine together than in those treated with either substance separately (p less than 0.01). The results indicate that age influences the arrhythmogenic action of lysophosphatidylcholine, and that epinephrine contributes to this effect. PMID- 2102805 TI - Towards a molecular understanding of contractility. AB - The contractile performance of the heart depends on the molecular force generators, the myosin crossbridges between thick and thin filaments. These are oscillating between two states, strong and weak, or force-generating and non force-generating. Calcium activation of the contractile machinery increases the probability of forming force-generating crossbridges, whereas the speed of contraction depends on the probability of returning force-generating crossbridges into weak ones. It is inversely related to the energetic cost of contraction. The probabilities or rate constants describing the transitional states of the force generators (and denoted as g and f) describe not only the kinetic properties of the contractile system but also its responsiveness to the calcium activator. The development of force depends not only on the free calcium ion concentration in the myoplasm, but also on calcium responsiveness which is dependent both on crossbridge kinetics and the calcium affinity of the regulatory protein, troponin. In future, it will be important to find out how all these molecular properties of the force-generators are affected in diseased states as well by pharmacological interventions, such as the application of novel cardiotonic drugs. PMID- 2102806 TI - Hemodynamic profile of amiodarone during acute and long-term administration in patients with ventricular dysfunction. AB - One of the potential adverse effects of anti-arrhythmic agents is an impairment of cardiac function as a result of their intrinsic negative inotropic properties. Amiodarone, in animals, also induces dose-related negative inotropic effects, in addition to coronary and systemic vasodilatation and slowing of the heart. Likewise, in most human studies, intravenous amiodarone gives rise to early systemic and coronary vasodilatation, followed by a reduction in contractility. Depending on the relative impact of these opposing effects on the left ventricle, the changes in heart rate, cardiac output and left ventricular filling pressure are variable. Particularly in patients with pre-existing ventricular dysfunction, cardiac pump function is impaired further when relatively high dosages of amiodarone are used without its solvent Tween 80. In contrast, fast bolus administrations, eg. 5 mg/kg amiodarone in 5 minutes, result in an improvement of cardiac output, albeit at the expense of an increase in left ventricular filling pressure. The latter observation suggests that intravenous amiodarone should be given with caution in patients with heart failure and elevated left ventricular filling pressures. When given by mouth, amiodarone does not have significant hemodynamic effects, other than a moderate reduction in heart rate and, occasionally, in diastolic blood pressure. Cardiac pump function is not affected, even in patients with ventricular dysfunction or heart failure, in whom chronic oral administration of the drug is well tolerated. PMID- 2102807 TI - Antibodies to xanthine oxidase: elevated levels in patients with acute myocardial infarction. AB - Circulating antibodies to whole dried cows' milk, previously reported to be elevated in patients with myocardial infarction, have been shown to be directed mainly to the bovine milk fat globule membrane. Human antibodies against the bovine milk fat globule membrane themselves interact primarily with the enzyme, xanthine oxidase. Comparison of anti-(xanthine oxidase) antibody levels in 107 patients, who had suffered a myocardial infarction, with those in 86 control subjects showed significantly higher IgM levels in the patients with myocardial infarction. No corresponding differences were found for IgG or IgA anti-(xanthine oxidase) antibodies. Total levels of IgM class immunoglobulins did not differ between patients and controls. Serial assays following myocardial infarction showed no evidence that raised levels of IgM anti-(xanthine oxidase) antibodies result from the infarction itself. PMID- 2102808 TI - Antioxidant protection against damage during cardiac ischemia and reperfusion: effect of dimercapto-propanol. AB - Oxygen-derived free radicals and their metabolites may contribute to the extension of cellular injury that occurs on reperfusion of the ischemic myocardium; and therapy directed against the toxic effects of reactive oxygen species has provided protection to the ischemic myocardium which undergoes subsequent reperfusion. We evaluated the effectiveness of dimercapto-propanol (1,2-dimercapto-propanol, British Anti-Lewisite, dimercaprol) to limit the extent of myocardial damage resulting from 60 minutes of severe ischemia followed by 30 minutes of reperfusion in the Langendorff-perfused rabbit heart. Dimercaptopropanol is a thiol agent, with two free sulfhydryl groups per molecule, which has no effect on glutathione status nor on the total tissue thiol pool. Pretreatment of the hearts with 10(-6) M dimercapto-propanol resulted in marked myocardial protection, measured in terms of preserved mechanical function and reduced creatine kinase release. On reperfusion less oxidative stress developed. The beneficial effects of dimercapto-propanol could not be explained by hemodynamic differences or effects on energy metabolism. In addition, it is unlikely that dimercapto-propanol acts as a free radical scavenger at the concentrations employed. The protection may be achieved by the drug keeping some key sulfhydryl groups of functional proteins in the reduced state. PMID- 2102809 TI - Mechanical and metabolic determinants of myocardial stunning in extracorporeally perfused pig hearts. AB - The purpose of this study was to apply step-wise multiple linear regression analysis retrospectively to an array of mechanical and metabolic measurements chosen because they had the potential to predict the extent of contractile recovery from a prescribed duration of myocardial ischemia. Data were acquired from the extracorporeally perfused, intact, working pig heart which was rendered regionally ischemic (60% reduction in anterior descending coronary flow) for 45 minutes and reperfused to aerobic levels for a final 30-50 minutes. Mechanical recovery was defined by the percentage systolic shortening and the area circumscribed by left ventricular pressure-segment length loops. Data were taken from 39 control hearts and from 16 hearts treated with oxfenicine, an agent which we have previously used to alter mechanical function by its interference with fatty acid metabolism. Despite the fixed nature of the protocol in affecting ischemic hypoperfusion, a wide range of mechanical responses encompassing hypo- and dyskinesis was produced during ischemia, followed by mechanical stunning during reflow. Of the parameters surveyed, regional indices of mechanical performance, together with perfusate pH and PCO2, best predicted recovery. Along with the heart rate, these predictors gave correlations of 0.875 for percentage systolic shortening and 0.766 for the length-pressure loop in control hearts. The analyses were also sensitive to the influence of pharmacological intervention with oxfenicine in that several parameters lost statistical significance for percentage systolic shortening and two were added (heart rate and end-diastolic length) for the length-pressure loop. Separate statistical models for oxfenicine treated hearts gave correlations of 0.905 for percentage systolic shortening and 0.915 for the length-pressure loop. The data suggest that step-wise multiple linear regression analysis provides new insights toward our understanding of the mechanisms of mechanical stunning in myocardial reperfusion. PMID- 2102810 TI - Effect of pretreatment with anipamil on a submaximal calcium paradox in the isolated rat heart. AB - Successive perfusion of a heart with a Ca(2+)-free and Ca(2+)-containing solution results in irreversible myocardial cell damage: the calcium paradox. Experiments were undertaken to assess whether pretreatment of rats with the new calcium antagonist anipamil (5 mg/kg body weight, twice daily for 5 days) protects the isolated heart against a submaximal calcium paradox. A submaximal calcium paradox was induced by successive perfusion with a Ca(2+)-free solution and a solution containing 0.1 mM Ca2+. Hearts from rats pre-treated with anipamil did not show a negative inotropic effect during control perfusion. During reperfusion in the presence of 0.1 Ca2+, after 10 minutes of Ca(2+)-free perfusion, creatine kinase release in hearts from treated rats was significantly less than in hearts from untreated rats (p less than 0.001). It is suggested that anipamil makes the sarcolemma less sensitive to conformational changes upon Ca2+ repletion. PMID- 2102811 TI - Properties of adult rat ventricular cells in long-term culture. AB - Adult mammalian cardiac myocytes in long-term culture offer advantages over intact heart tissue and freshly isolated ventricular cell preparations for a variety of experimental studies. To characterize this preparation in detail, we have examined the physiological properties of isolated adult rat ventricular cells maintained in culture for 10-14 days. Adult rat myocytes in longterm culture contracted spontaneously, with electrical coupling of adjacent cells, at 1-3 Hz. Most myocytes showed myofibrils with well-developed mitochondria and transverse tubular systems. They showed predominantly the V1 type myosin heavy chain isoform. In standard physiological superfusion media (pH 7.35), the intracellular pH of cultured cells measured with 2',7'-bis-carboxyethyl carboxyfluorescein (BCECF) was 7.26 +/- 0.03, and was regulated by an amiloride sensitive Na-H exchanger. The time-averaged free intracellular Ca2+ level of cultured adult rat myocytes measured with fura-2 at an extracellular Ca2+ level of 1 mM was 99.0 +/- 16.8 nM. Ouabain, Bay k 8644 or isoproterenol caused a significant rise in time-averaged intracellular [Ca2+], while the dihydropyridine Ca channel blocker nifedipine induced a decrease in intracellular [Ca2+]. Measurements of contractile state with an optical-video system demonstrated that ouabain. Bay k 8644, isoproterenol, or elevated extracellular [Ca2+] increased the amplitude of cell motion and the rates of both shortening and relaxation, while nifedipine lowered them. Microelectrode impalements indicated a resting potential of -75 +/- 1 mV and an action potential amplitude of 100 +/- 2 mV. Exposure of cultured adult rat cardiocytes to the thyroid hormone triiodothyronine (10 nM) for 48 hours resulted in a 2-fold increase in NaK-ATPase alpha-1 catalytic subunit mRNA accumulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102812 TI - Regulatory effects of IL-4 on human B-cell response to IL-2. AB - Interleukin-4 (IL-4) counteracts a number of the direct effects of interleukin-2 (IL-2) on B-cells. We here summarize and extend our results, obtained in two different experimental systems, on the antagonism between these two major interleukins. IL-4 inhibits the effect of IL-2 on the proliferation as well as the differentiation of B-type chronic lymphocytic leukemia (B-CLL) cells. When B CLL cells are activated by anti-mu Ab in the presence of IL-4, this latter enhances the expression of the p55 as well as the p70/75 chain of the IL-2 receptor. In contrast IL-4 profoundly suppresses the number of high affinity binding sites for IL-2 on in vitro activated B-CLL cells. Such a discrepancy between the suppression of IL-2 binding sites and the enhancement of each component of the heterodimeric IL-2 receptor, is as far as we know, yet undescribed. The interaction of IL-4 with its own receptors might influence the state of p55-p70/75 complex association or act on a third subunit of the IL-2 receptor. When used alone, IL-4 enhances the expression of other activation molecules by B-CLL cells: CD23, DR antigen. Similarly IL-4 can concomitantly enhance the specific response of normal B-cells while suppressing the action of IL-2. When normal human B-cells are specifically stimulated by an insolubilized antigen, IL-4 alone induces an expansion of the number of specific antigen binding cells. In contrast IL-4 profoundly suppresses the generation of antigen induced IL-2-dependent specific IgM antibody forming cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102813 TI - Depressed IL-1 production by chronic GVHD dermal fibroblasts. AB - Chronic Graft-versus-Host disease (GVHD) is characterized by overt immunosuppression. In addition, the skin is a major anatomical site affected in chronic GVHD for reasons not yet known. Increased collagen deposition, a mononuclear cell infiltrate in the dermis as well as loss of fat and appendages, are observed in the skin. The inflammatory cytokine IL-1 was shown to affect fibroblast proliferation and secretory activities. In the present study, IL-1 generation by dermal fibroblasts, of chronic GVHD or control mice, was assessed. It was shown that two sequential signals are needed for IL-1 generation by dermal fibroblasts; priming by lymphokines/cytokines followed by a challenge with LPS. A variety of recombinant lymphokines and cytokines (G/M-CSF, IL-2, TNF, IL-1 beta and IFNs alpha, beta and gamma) were shown to be efficient in priming dermal fibroblasts for IL-1 generation. IL-1 activity in dermal fibroblasts, most probably of the IL-1 alpha species, was located in frozen-thawed cell lysates or associated to the cell membrane, though not secreted into the culture fluids. Dermal fibroblasts from chronic GVHD mice manifested a pronounced depression in IL-1 generation upon stimulation with exogenous lymphokines/cytokines and LPS. This was observed over a wide range of concentrations of lymphokines/cytokines and LPS. The depressed ability of chronic GVHD fibroblasts to generate IL-1 was pronounced even after few passages of the cells in vitro, and upon stimulation in culture outside the suppressive milieu of the animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102814 TI - Interleukin-3 induces proliferation but not lymphokine activated killer activity from human and murine mononuclear cells. AB - Recombinant IL-3 (rIL-3) is a potent colony stimulating factor capable of stimulating early hematopoietic pluripotential progenitor cells and of supporting the differentiation of multiple cells. IL-3 has also been shown to have effects on mature, differentiated circulating cells including eosinophils and T cells. We evaluated the role of exogenous rIL-3 in the generation of cells with LAK activity from murine splenocytes and human bone marrow, spleen, unseparated PBMC and purified null cell preparations. rIL-3 was unable to generate lytic activity from any of these populations by itself and appeared to decrease LAK activity in bone marrow cultures containing high dose IL-2, (bone marrow derived cells (n = 3) with LAK activity for fresh tumor, mean lytic units(LU) 94.6 +/- 63.5 vs 32.8 +/- 44.8 for IL-2 and IL-2 plus IL-3 cultures, respectively p2 less than 0.05). Unlike previous reports testing murine cells, IL-3 priming and subsequent culture in IL-2 of human unseparated bone marrow cells or human or murine splenocytes, failed to generate long-term cultures with lytic activity. IL-3 did, however, induce a dose dependent stimulation of bone marrow and null cell preparations (mean null cell stimulation (3H Thymidine incorporation) with IL-3, 436 +/- 168 cpm vs 9802 +/- 9799 cpm, for 0 vs 10(3) units of IL-3, respectively n = 4, p2 less than 0.05). Furthermore, in bone marrow, unseparated PBMC and null cell cultures, the addition of rIL-3 generated characteristic large blastic appearing cells with prominent basophilic granules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102815 TI - Regulation of the ATP-sensitive potassium channel. PMID- 2102816 TI - Type I and type II genes for the chlorophyll a/b-binding protein in the gymnosperm Pinus sylvestris (Scots pine): cDNA cloning and sequence analysis. AB - A cDNA library was constructed from mRNA prepared from light-treated seedlings of Scots pine (Pinus sylvestris L.) and cDNAs for the chlorophyll a/b-binding protein LHC-II were identified using a pea gene as the heterologous probe. Three cDNA clones were sequenced. The deduced amino acid sequences of two of the genes corresponded to Type I and one to Type II LHC-II proteins which were ca. 90% homologous to their angiosperm counterparts. The transit peptides of the Scots pine preLHC-II showed features common to angiosperm transit peptides. The three cDNAs had a 70 to 75% preference for G + C in the third base position. CpG and GpC profiles and degenerate codon position bias suggested that two of the corresponding genes lie within CpG islands. PMID- 2102817 TI - Cloning and characterization of a cDNA encoding the wheat (Triticum durum Desf.) CM16 protein. AB - A Triticum durum cDNA library prepared from developing endosperm (22 days after flowering (DAF] was screened using synthetic oligonucleotide probes covering part of the CM3 and CM16 N-terminal protein sequences. A full-length cDNA clone (pTd78) encoding the CM16 protein (chloroform/methanol-soluble protein) was isolated and characterized. To our knowledge this is the first characterization of a clone coding for a wheat CM protein. The CM16 protein is synthesized as a preprotein with a signal peptide of 24 residues, the molecular weight of the mature protein being 13,438 Da. As other members of the cereal trypsin/alpha amylase inhibitor family, the CM16 protein contains 10 cysteine residues, their position being well conserved. In developing endosperm the highest level of CM16 mRNA was detected at mid-maturation. PMID- 2102818 TI - Deletion analysis of a zein gene promoter in transgenic tobacco plants. AB - A zein gene (Z4) promoter containing 886 bp upstream from the transcription start site has been shown previously to be active specifically in the endosperm of transgenic tobacco seeds. To investigate the region required for this tissue specific activity, deletions of the Z4 promoter were constructed and placed upstream of the beta-glucuronidase (GUS) reporter gene. When these deletions were tested in transgenic tobacco plants, seed-specific GUS activity, which reached a peak between 15 and 19 DAP, was observed for promoters extending from -886 to 174. Interestingly, the 174 bp promoter lacked the complete 15 bp consensus sequence found in the same position in all zein genes so far sequenced. With the next shorter promoter in the deletion series (79 bp), which just included the CAAT and TATA elements, negligible GUS activity was observed in seeds. The results demonstrated that 174 bp upstream of the transcription start site are sufficient for tissue-specific and temporally regulated activity of the Z4 promoter in tobacco. At most, two-fold enhanced activity was observed with additional 5' sequences up to -886. PMID- 2102819 TI - Regulation of expression of a wound-inducible tomato inhibitor I gene in transgenic nightshade plants. AB - A wound-inducible proteinase Inhibitor I gene from tomato containing 725 bp of the 5' region and 2.5 kbp of the 3' region was stably incorporated into the genome of black nightshade plants (Solanum nigrum) using an Agrobacterium Ti plasmid-derived vector. Transgenic nightshade plants were selected that expressed the tomato Inhibitor I protein in leaf tissue. The leaves of the plants contained constitutive levels of the inhibitor protein of up to 60 micrograms/g tissue. These levels increased by a factor of about two in response to severe wounding. Only leaves and petioles exhibited the presence of the inhibitor, indicating that the gene exhibited the same tissue specificity of expression found in situ in wounded tomato leaves. Inhibitor I was extracted from leaves of wounded transformed nightshade plants and was partially purified by affinity chromatography on a chymotrypsin-Sepharose column. The affinity-purified protein was identical to the native tomato Inhibitor I in its immunological reactivity and in its inhibitory activity against chymotrypsin. The protein exhibited the same Mr of 8 kDa as the native tomato Inhibitor I and its N-terminal amino acid sequence was identical to that of the native tomato inhibitor I, indicating that the protein was properly processed in nightshade plants. These experiments are the first report of the expression of a member of the wound-inducible tomato Inhibitor I gene family in transgenic plants. The results demonstrate that the gene contains elements that can be regulated in a wound-inducible, tissue specific manner in nightshade plants. PMID- 2102820 TI - Inheritance and effect on ripening of antisense polygalacturonase genes in transgenic tomatoes. AB - The role of the cell wall hydrolase polygalacturonase (PG) during fruit ripening was investigated using novel mutant tomato lines in which expression of the PG gene has been down regulated by antisense RNA. Tomato plants were transformed with chimaeric genes designed to express anti-PG RNA constitutively. Thirteen transformed lines were obtained of which five were analysed in detail. All contained a single PG antisense gene, the expression of which led to a reduction in PG enzyme activity in ripe fruit to between 5% and 50% that of normal. One line, GR16, showed a reduction to 10% of normal PG activity. The reduction in activity segregated with the PG antisense gene in selfed progeny of GR16. Plants homozygous for the antisense gene showed a reduction of PG enzyme expression of greater than 99%. The PG antisense gene was inherited stably through two generations. In tomato fruit with a residual 1% PG enzyme activity pectin depolymerisation was inhibited, indicating that PG is involved in pectin degradation in vivo. Other ripening parameters, such as ethylene production, lycopene accumulation, polyuronide solubilisation, and invertase activity, together with pectinesterase activity were not affected by the expression of the antisense gene. PMID- 2102821 TI - Isolation and characterization of six pathogenesis-related (PR) proteins of Samsun NN tobacco. AB - The purification to homogeneity of pathogenesis-related (PR) proteins R and S from Nicotiana tabacum cv. Samsun NN leaves has been achieved by using a combination of conventional and high-performance chromatographic supports. The same procedure allowed the purification and the characterization of four other proteins which displayed some properties characteristic of tobacco PR proteins and were shown to accumulate in tobacco leaves in response to virus infection. They can be, therefore, considered as new tobacco PR proteins which we designate as PR-s1, -s2, -r1 and -r2. The relative electrophoretic mobilities (Rf) under non-denaturing conditions were estimated to 0.30 for PR-r1 and -r2, 0.25 for Pr R, 0.20 for PR-s1 and -s2 and 0.15 for PR-S. On SDS gels PR proteins R and S possessed the same apparent molecular weight (Mr 24,000) as did PR-proteins s1 and r1 (Mr 14,500) and PR-s2 and -r2 (Mr 13,000). However, proteins s1, s2, r1 and r2 had identical electrophoretic mobilities on SDS gels when the loading sample buffer contained no reducing agent. Polyclonal antisera were raised against PR proteins R and S and used in immunoblotting experiments. Proteins R and S were shown to be serologically closely related. No cross-reaction was detected with any of the four new tobacco PR proteins r1, r2, s1 and s2 or with the previously described PR proteins, i.e. PR-1a, -1b, -1c, -2, -N, -O, -P and Q. PMID- 2102822 TI - The single-copy actin gene of Phytophthora megasperma encodes a protein considerably diverged from any other known actin. AB - This paper reports the cloning and sequencing of a Phytophthora megasperma actin gene. Sequence analysis revealed that the gene does not contain introns and encodes a putative actin protein remarkably diverged from any other known actins. Genomic Southern analysis indicates that there is a single actin gene per haploid genome, which is actively transcribed in vivo, as revealed by S1 mapping of the transcripts. The transcripts are heterogeneous in size because they have different 3' termini, none of which contains the conventional AATAAA polyadenylation signal. PMID- 2102824 TI - Isolation and characterization of a highly repetitive DNA of Brassica campestris. PMID- 2102823 TI - Characteristics of a strong promoter from figwort mosaic virus: comparison with the analogous 35S promoter from cauliflower mosaic virus and the regulated mannopine synthase promoter. AB - A segment of DNA from the genome of figwort mosaic virus (FMV) strain M3 possesses promoter activity when tested in electroporated protoplasts from, and transgenic plants of, Nicotiana tabacum cv. Xanthi nc. The 1.1 kb DNA segment, designated the '34S' promoter, is derived from a position on the FMV genome comparable to the position on the cauliflower mosaic virus (CaMV) genome containing the 35S promoter. The 34S and 35S promoters show approximately 63% nucleotide homology in the TATA, CCACT, and -18 to +1 domains, but in sequences further upstream the homology drops below 50%. Promoter activities were estimated using beta-glucuronidase and neomycin phosphotransferase II reporter gene systems. The activity of the 34S promoter segment approximates that of the 35S promoter in both protoplast transient expression assays and in stably transformed tobacco plants. Truncation of 5' sequences from the 34S promoter indicates that promoter strength depends upon DNA sequences located several hundred nucleotides upstream from the TATA box. In leaf tissue the 34S promoter is 20-fold more active than the mannopine synthase (MAS) promoter from Agrobacterium tumefaciens T-DNA. The 34S promoter lacks the root-specific and wound-stimulated expression of the MAS promoter, showing relatively uniform root, stem, leaf, and floral activities. PMID- 2102825 TI - A nodule-specific sequence encoding a methionine-rich polypeptide, nodulin-21. PMID- 2102826 TI - Nucleotide sequence encoding a slow allele of Adh1 in pearl millet. PMID- 2102827 TI - Inhibition of flower pigmentation by antisense CHS genes: promoter and minimal sequence requirements for the antisense effect. AB - Introduction of a constitutive antisense full-length chalcone synthase (CHS) cDNA gene in petunia can result in an inhibition of flower pigmentation. We have evaluated some of the factors which may be important for the effectiveness of an antisense CHS gene. Antisense CHS genes encoding half-length or quarter-length RNA complementary to the 3' half of CHS mRNA are able to affect flower pigmentation, while a gene encoding RNA complementary to the 5' half of CHS mRNA did not show phenotypic effects in transgenic petunia plants. We demonstrate that the RNA encoded by the latter gene has a much lower average steady-state level in leaf tissue than the RNAs encoded by the other antisense gene constructs. We have compared the CaMV 35S and endogenous CHS promoter strengths and intrinsic stabilities of sense and antisense CHS RNAs. From the data we conclude that the constitutive antisense CHS genes are not likely to provide an excess of antisense RNA compared to the CHS mRNA derived from the endogenous genes. Effective inhibition of flower pigmentation is also observed when the antisense CHS gene is under control of the homologous CHS promoter. The results indicate that the mechanism of antisense inhibition cannot solely operate via RNA duplex formation between sense and antisense RNA. PMID- 2102828 TI - Identification and cDNA cloning of a new nodule-specific gene, Nms-25 (nodulin 25) of Medicago sativa. AB - A new nodule-specific gene, Nms-25 (nodulin-25), was identified in cDNA clones isolated from a nodule-specific cDNA library of Medicago sativa. The first transcript of this gene appeared 9 days after inoculation of the roots with Rhizobium meliloti. The time of expression and the quantity of the transcripts of the Nms-25 gene was similar to that of leghemoglobin genes suggesting a similar regulation. A protein of 246 amino acids could be deduced from a full-length cDNA clone. The first 24 amino acids at the N-terminal end of this protein formed a signal sequence which might direct membrane transport into the peribacteroid space. Using different predictive methods the signal sequence cleaved protein was tentatively predicted to be a water-soluble enzyme, but not hydrolase. PMID- 2102829 TI - The double-stranded RNA associated with the '447' cytoplasmic male sterility in Vicia faba is packaged together with its replicase in cytoplasmic membranous vesicles. AB - The 447 male sterility trait in Vicia faba is strictly correlated with the presence of well-defined membranous vesicles or 'cytoplasmic spherical bodies' not found in fertile isogenic maintainer plants, and by the occurrence of a discrete high molecular weight double-stranded RNA. We have purified these cytoplasmic membranous vesicles and find that they contain the dsRNA together with an RNA-dependent RNA polymerase whose activity depends upon the presence of Mg2+, requires the four-nucleoside triphosphates and is unaffected by inhibitors of cellular transcriptases, e.g. alpha-amanitin and Actinomycin D. The dsRNA can be labelled in vitro by incubating the cytoplasmic vesicles with radioactive NTPs, and the RNA synthesized in vitro is also in a double-stranded form as judged by its resistance to RNase digestion at high salt and its behaviour upon CF-11 chromatography. Treatment of the vesicles with a non-ionic detergent releases the dsRNA in the form of a complex with the RNA-dependent RNA polymerase. The enzyme can still carry out the specific synthesis of dsRNA in these solubilized complexes. The cytoplasmic vesicles therefore isolate this vertically transmitted, self-replicating dsRNA from the cellular milieu: the possible mode of action and relevance of this novel genetic element to the 447 cytoplasmic male sterility trait are discussed. PMID- 2102830 TI - Tissue-specific expression directed by an Arabidopsis thaliana pre-ferredoxin promoter in transgenic tobacco plants. AB - We have isolated and analyzed a pre-ferredoxin gene from Arabidopsis thaliana. This gene encodes a 148 amino acid precursor protein including a chloroplast transit peptide of 52 residues. Southern analysis shows the presence of a single copy of this ferredoxin (Fd) gene in the A. thaliana genome. Its expression is tissue-specific and positively affected by light. Response times, both to dark and light conditions, are remarkably rapid. A chimeric gene consisting of a 1.2 kb Fd promoter fragment fused to the beta-glucuronidase reporter gene was transferred to tobacco. This fusion gene is expressed in a tissue-specific way; it shows high levels of expression in green leaves, as compared to root tissue. PMID- 2102832 TI - Wound-inducible potato inhibitor II genes: enhancement of expression by sucrose. AB - Expression of a chimeric potato Inhibitor II-CAT gene in transgenic tobacco plants was enhanced 50-fold when leaf tissue was floated on solutions containing 1% sucrose. The expression of the chimeric gene was also enhanced when leaf sections were floated on solutions of glucose, fructose, and maltose, but not when floated on solutions of mannitol. The increased expression due to sucrose was found to be correlated with an increase in CAT mRNA. Thus, the carbohydrates or their metabolic products may control Inhibitor II gene expression by regulating transcription. Levels of potato Inhibitor II proteins in leaf sections from young potato plants floated on 3% sucrose solutions increased 3-fold compared to leaf sections floated on water, supporting the possibility that sucrose may have a role in regulating or enhancing the expression of wound inducible proteinase inhibitor genes in potato tissues. It is suggested that the Inhibitor II gene and perhaps other genes regulated by sucrose may contain a specific 'sucrose enhancer' that strongly increases transcription of genes already active at low levels. PMID- 2102831 TI - Diverse soybean actin transcripts contain a large intron in the 5' untranslated leader: structural similarity to vertebrate muscle actin genes. AB - Plant actins are encoded by complex and highly divergent multigene families. Despite the general lack of intron conservation in animal, fungal and protist actin genes, evidence is presented which indicates that higher plant actin genes have an untranslated leader exon with structural similarity to that found in vertebrate actin genes. All functional higher plant actin genes sequenced to date contain a potential intron acceptor site in the 5' untranslated region 10 to 13 nucleotides upstream of the initiator ATG. A leader specific cDNA probe hybridized to sequences over 1.0 kbp upstream from the coding region confirming the presence of an upstream exon. Primer extension of mRNA with gene-specific oligonucleotides was used to analyze the 5' untranslated exon and leader intron from four divergent soybean actin genes, SAc3, 4, 6 and 7. The 5' ends of all four mRNAs are heterogeneous. The consensus promoter elements of the SAc7 actin promoter were identified. Gene specific primer extension sequencing of actin mRNAs indicated that splicing of the 5' leader intron occurred at the predicted acceptor site in SAc6 and SAc7. The SAc6 and SAc7 5' untranslated exons are small (88-111 nt) and the leader introns are relatively large (844-1496 nt). The presence of an intron within the 5' RNA leader and an intron which splits a glycine codon at position 152 in all plant actin genes and all vertebrate muscle actin genes suggests that these structures may have been conserved due to a functional role in actin expression. The 5' regions of these two soybean actin genes contain many unusual features including (CT) repeats and long stretches of pyrimidine-rich DNA. The possible roles of the upstream exon/intron and the C + T rich regions are discussed. PMID- 2102833 TI - The isolation and sequence analysis of two seed-expressed acyl carrier protein genes from Brassica napus. AB - Genomic Southern blot analysis of Brassica napus DNA indicates that seed expressed acyl carrier protein (ACP) is encoded by a multigene family of some 35 genes/haploid genome. Two genomic clones encoding B. napus ACP have been isolated and sequenced. The coding sequences of the 2 respective genes were found to be perfectly homologous to 2 distinct B. napus seed-expressed cDNAs and therefore represent seed-expressed forms of ACP. The 2 genomic ACP sequences share 94% homology within their coding sequences. Both genes are interrupted by 3 intervening sequences whose position within the 2 coding sequences is conserved. RNase protection studies were used to map the transcription start site of one of the genes and to provide further evidence that the gene is seed-expressed. The expression of a sub-group of the ACP gene family was found to be developmentally regulated in concert with the storage lipid synthetic phase of seed development. The coding sequence of both B. napus genes are highly homologous (96% and 93% respectively) to a Brassica campestris ACP cDNA sequence, suggesting that they may have evolved from this ancestral gene. PMID- 2102834 TI - Isolation of single-copy-sequence clones from a yeast artificial chromosome library of randomly-sheared Arabidopsis thaliana DNA. AB - We describe the construction of a yeast artificial chromosome (YAC) library from the Arabidopsis thaliana genome. Randomly sheared high molecular weight source DNA was extracted from frozen, ground leaf tissue and blunt-end-ligated to the vector pYAC3. By size-fractionating the ligation products, we achieved an average clone size of 150 kb. Approximately 6% of the YACs contained inserts from the chloroplast genome. We screened clones equivalent to greater than four A. thaliana haploid nuclear genomes and isolated YACs homologous to five single-copy sequence probes. The library should be useful for chromosome walking and genome mapping experiments. In addition, the approach used for its construction should be applicable to other higher plant species. PMID- 2102835 TI - Benzyladenine induces the appearance of LHCP-mRNA and of the relevant protein in dark-grown excised watermelon cotyledons. AB - Cotyledons were excised from imbibed watermelon seeds, grown for 4 days in darkness on water or 10 microM benzyladenine (BA) and then tested for the presence of the light-harvesting chlorophyll a/b protein (LHCP) and its mRNA. LHCP was assayed immunologically by western blotting of SDS gels: the protein was present in plastids, but it was not recovered with the thylakoid fraction. Antibodies directed against LHCP precipitated a 32 kDa polypeptide from translation products of poly(A) RNA of cotyledons only if these had been grown on BA. Taken together the data suggest that in absence of light cytokinins are necessary for the maintenance of a detectable level of LHCP-mRNA as well as for synthesis of the protein. PMID- 2102836 TI - Quantitation of chloramphenicol acetyl transferase in transgenic tobacco plants by ELISA and correlation with gene copy number. AB - A monoclonal antibody to chloramphenicol acetyl transferase (CAT) was used in an indirect competitive enzyme immunoassay (ELISA) for the quantitation of CAT in leaf extracts of eighteen transgenic tobacco plants containing the CAT gene fused to the cauliflower mosaic virus 35S promoter. The ELISA could be used to quantify CAT when present in extracts at 20 ng/ml. Enzymatic activity and electrophoretic mobility of CAT in these extracts was not different from CAT from Escherichia coli. Concentrations of CAT in these transgenic plants ranged from 79 to 732 ng CAT/mg protein. The average coefficient of variation among three replicate samples was 15%. All plants were sampled on two separate occasions. The CAT concentrations often varied between the two sampling dates. We determined the CAT gene copy number and the number of independently segregating loci in each plant by Southern blot analysis and progeny testing. We found no significant differences in CAT expression among all ten plants with a single CAT gene. We also found a significant correlation between CAT gene copy number and the level of CAT expressed in each plant, although plants with one gene copy sometimes had more CAT than plants with more than one gene copy. In this population, therefore, gene copy number contributed more to the variation in CAT expression than did position effects. PMID- 2102837 TI - Cytokinin enhancement of the light induction of nitrate reductase transcript levels in etiolated barley leaves. AB - To investigate the molecular mechanism of cytokinin regulation of nitrate reductase (NR) activity, the influence of benzyladenine (BA) on the level of NR transcript was studied in etiolated barley leaves using a barley NR cDNA as a probe. Northern blot analyses of the levels of NR poly (A)+ RNA indicate that the amount present is proportional to the concentration of BA (2 x 10(-8) to 2 x 10( 4) M) applied to the leaves. Enhancement of NR mRNA by 2 x 10(-5) M BA was clearly detected after 15 minutes of exposure of the leaves to light. The enhancement is cytokinin-specific and adenine is ineffective. Brief treatment with the protein synthesis inhibitor, cycloheximide, inhibited BA-enhanced NR activity but did not inhibit BA-enhanced NR transcript level, thus the enhancement was independent of concurrent protein synthesis. Nuclear runoff transcription studies showed that the enhancement of NR mRNA was at least partially due to increased transcription rates. PMID- 2102838 TI - High-level expression of tuberous root storage protein genes of sweet potato in stems of plantlets grown in vitro on sucrose medium. AB - Sporamin, the tuberous root storage protein of the sweet potato, accounts for about 60 to 80% of the total soluble protein of this organ. The amount of sporamin present in other organs is very low, or even not detectable, in the normal field-grown plants. However, the stem of sweet potato plantlets grown axenically on agar medium containing sucrose was found to accumulate large amounts of sporamin. Two-dimensional gel electrophoretic profiles of sporamin precursors synthesized in vitro by poly(A)+ RNA are indistinguishable between tuberous roots of the field-grown plants and stems of the axenically cultured plants, suggesting that an essentially identical set of the members of sporamin multigene family are expressed in these two organs under different growth conditions. Transgenic tobacco plants having a CAT (chloramphenicol acetyltransferase) fusion gene with the 5' upstream region of a sporamin A gene, gSPO-A1, show preferential expression of CAT activity in stems when the plants are maintained in axenic culture on sucrose medium as is the case for sporamin in sweet potato. Deletion analysis revealed that the DNA sequence of gSPO-A1 between -94 and -305, relative to the transcription start site, is important for its expression in tobacco. This region contains two of the previously postulated putative regulatory elements conserved between sporamin A and B genes. PMID- 2102839 TI - Effect of dark phases and temperature on the chlorophyll a/b binding protein mRNA level oscillations in tomato seedlings. AB - External parameters (e.g. light/dark alterations and temperature) were tested for their ability to influence the expression pattern of the chlorophyll a/b binding protein (cab) genes and the small subunit of RuBPC/Oase (rbcS) genes. Particular interest was focused on the alterations of diurnal/circadian oscillation patterns of cab mRNA levels. Chlorophyll a/b binding protein and small subunit of RuBPC/Oase mRNA oscillations were observed in tomato seedlings grown without environmental perturbations (constant illumination and temperature), indicating that these genes are controlled by an endogenous rhythm. The rhythmic fluctuation patterns revealed a period of about 32 hours and a weekly expressed amplitude. A several-fold increase of the cab mRNA amplitude and a reduction of the period to about 24 hours (circadian) was monitored after exposure of the tomato seedlings to 3, 6 or 9 hours of darkness. The elevated amplitude disappeared at consecutive days if seedlings were not exposed to further dark phases. A circadian rhythm with clearly expressed cab mRNA amplitudes was also present after the plants had been transferred to darkness at various circadian times. However, under those circumstances the time points of maximum and minimum transcript levels were shifted by respective hours. Alteration of the growth temperature from 24 degrees C to 10 degrees C or 30 degrees C at constant illumination or in a light/dark cycle resulted in a reduction of the amplitudes or of the steady-state mRNA levels. Such extreme temperature changes do not induce or enhance the diurnal cab mRNA oscillations. PMID- 2102840 TI - Identification of a putative rol B gene on the TR-DNA of the Agrobacterium rhizogenes A4 Ri plasmid. PMID- 2102841 TI - Genomic nucleotide sequence of four rice (Oryza sativa) actin genes. PMID- 2102842 TI - PSTV sequence similarity to large rRNA. PMID- 2102843 TI - The expression of phytohemagglutinin genes in Phaseolus vulgaris is associated with organ-specific DNA methylation patterns. AB - Using methylation sensitive restriction enzymes and DNA gel blot analyses, we have examined DNA methylation patterns at the chromosomal locus harboring the two phytohemagglutinin genes of Phaseolus vulgaris. In cotyledons, where the genes are highly expressed, several sites have become undermethylated, whereas the methylation status of other sites remains constant, both in cotyledons and in other organs. Taken together with measurements of mRNA levels, these studies provide evidence that organ-specific changes in DNA methylation patterns are associated with the organ-specific expression of nuclear genes in a dicotyledonous plant. PMID- 2102844 TI - Isolation and nucleotide sequence of a genomic clone encoding a new Brassica napus napin gene. PMID- 2102845 TI - Partial nucleotide sequence from enigmatic dsRNAs in Phaseolus vulgaris. PMID- 2102846 TI - Molecular cloning of cDNAs for auxin-induced mRNAs and developmental expression of the auxin-inducible genes. AB - By differential hybridization, two auxin-inducible cDNA clones (lambda SAR1 and lambda SAR2) have been isolated from a cDNA library constructed to poly(A)+ mRNA from auxin-treated strawberry receptacles. Both the clones have been used as probes to study the expression of the auxin-induced genes in pollinated and unpollinated fruits of various stages of development and in different organs. A high level of auxin-induced mRNAs is found in pollinated fruits as compared to unpollinated fruits of the same age, suggesting that the expression of the auxin induced genes is developmentally regulated and the level of auxin-induced mRNAs is regulated by endogenous auxin. Furthermore, our data on the expression of lambda SAR1 and lambda SAR2 genes in pollinated and unpollinated fruits revealed a positive correlation between growth of strawberry fruit and the induction of mRNA corresponding to the lambda SAR1 and lambda SAR2 clones. Ethylene has no effect on the expression of the auxin-induced mRNAs. lambda SAR1 mRNA is not detected in other parts of strawberry plants whereas lambda SAR2 mRNA is present in roots. Furthermore, mRNA corresponding to lambda SAR1 and lambda SAR2 is not detected in other auxin-responsive plant systems such as pea epicotyls and bean explants. PMID- 2102847 TI - Classification and characterization of the rice alpha-amylase multigene family. AB - To establish the size and organization of the rice alpha-amylase multigene family, we have isolated 30 alpha-amylase clones from three independent genomic libraries. Partial characterization of these clones indicates that they fall into 5 hybridization groups containing a total of 10 genes. Two clones belonging to the Group 3 hybridization class have more than one gene per cloned fragment. The nucleotide sequence of one clone from Group 1, lambda OSg2, was determined and compared to other known cereal alpha-amylase sequences revealing that lambda OSg2 is the genomic analog of the rice cDNA clone, pOS103. The rice alpha-amylase genes in Group 1 are analogous to the alpha-Amy1 genes in barley and wheat. lambda OSg2 contains sequence motifs common to most actively transcribed genes in plants. Two consensus sequences, TAACAAGA and TATCCAT, were found in the 5' flanking regions of alpha-amylase genes of rice, barley and wheat. The former sequence may be specific to alpha-amylase gene while the latter sequence may be related to a 'CATC' box found in many plant genes. Another sequence called the pyrimidine box (TCCTTTTTC) was found in the alpha-amylase genes as well as other genes regulated by gibberellic acid (GA). Comparisons based on amino acid sequence alignment revealed that the multigene families in rice, barley and wheat shared a common ancestor which contained three introns. Some of the descendants of the progenitor alpha-amylase gene appear to have lost the middle intron while others maintain all three introns. PMID- 2102849 TI - Down-regulation of phytochrome mRNA abundance by red light and benzyladenine in etiolated cucumber cotyledons. AB - Northern blot analysis revealed that a single 4.2 kb phytochrome mRNA species was detectable in cotyledons excised from five-day-old etiolated cucumber seedlings. Intact etiolated five-day-old cucumber seedlings were given a red light or benzyladenine treatment, and cotyledons were harvested at various times following treatment. The abundance of phytochrome mRNA in the cotyledons was quantitated using 32P-labeled RNA probes and slot blot analysis. By 2 h after irradiation the phytochrome mRNA level was reduced to 40% of the initial abundance and reaccumulation began by 3 h after irradiation. Reaccumulation of phytochrome mRNA to the time-zero dark control level was achieved by 10 h after treatment. A decrease in phytochrome mRNA abundance was evident by 2 h after benzyladenine treatment, and a maximal reduction to 45% of the time-zero dark control was attained by 4 h after treatment. No recovery of the phytochrome mRNA level was evident by 8 h after benzyladenine treatment. The abundance of actin mRNA was unaffected by benzyladenine treatment. PMID- 2102848 TI - Yeast RAS2 affects cell viability, mitotic division and transient gene expression in Nicotiana species. AB - Overexpression of the budding yeast RAS2 gene in Nicotiana plumbaginifolia cells revealed that RAS2 acted as 'suicide' gene in freshly isolated protoplasts from leaves and blocked cell proliferation in cell suspension-derived protoplasts. Among a series of genes tested (such as npt II, CDC35, PDE2), RAS2 was the only one to block the expression of the cat gene, as measured in a transient gene expression assay. Another ras gene, v-Ha-ras, had similar effects. Furthermore, the RAS2 effect was species-specific and depended on the modulation of hormonal metabolism in the transfected cells, while no differences were noticed between the normal and the activated val19 gene. Transfected plant cells are shown to synthesize a RAS2 protein of the same electrophoretic mobility as the yeast RAS2 product. The results are discussed in the broader context of the evolutionarily conserved ras genes involved in vital cellular functions. PMID- 2102850 TI - Isolation and sequencing of cDNA clones encoding ethylene-induced putative peroxidases from cucumber cotyledons. AB - A cDNA library from ethephon-treated cucumber cotyledons (Cucumis sativus L. cv. Poinsett 76) was constructed. Two cDNA clones encoding putative peroxidases were isolated by means of a synthetic probe based on a partial amino acid sequence of a 33 kDa cationic peroxidase that had been previously shown to be induced by ethylene. DNA sequencing indicates that the two clones were derived from two closely related RNA species that are related to published plant peroxidase sequences. Southern analysis indicates that there are 1-5 copies in a haploid genome of a gene homologous to the cDNA clones. The deduced amino acid sequences are homologous with a tobacco (55% sequence identity), a horseradish (53%), a turnip (45%), and a potato (41%) peroxidase. The cloned sequences do not encode the 33 kDa peroxidase from which the original synthetic probe was been derived, but rather other putative peroxidases. An increase in the level of mRNA is evident by 3 hours after ethephon or ethylene treatment and plateaus by 15 hours. PMID- 2102851 TI - The minimum functional length of pre-mRNA introns in monocots and dicots. AB - When exogenous genes are to be expressed in transgenic plants, their RNAs must be correctly processed. To gain information useful for predicting whether foreign introns will be accurately spliced, we have analysed the processing of an artificial gene in maize and Nicotiana plumbaginifolia protoplasts. A synthetic plant intron, devised to contain the elements necessary for pre-mRNA splicing in dicots, was found to be efficiently spliced in a monocot (maize) transient expression system. A series of deletion mutants of the synthetic intron was constructed to assess the minimum functional intron length. In both monocots and dicots this was found to be between 70 and 73 nt. This length requirement is similar to that seen in vertebrates, but significantly greater than that in fungi and insects. PMID- 2102852 TI - Phylogenetic relationship of zeins and coixins as determined by immunological cross-reactivity and Southern blot analysis. AB - Zeins from Zea mays L cv. Maya and coixins from Coix lacryma-jobi L. cv. Adlay were fractionated to obtain alpha-, beta-, and gamma-zein and alpha-, beta-, and gamma-coixin. The alpha-coixins were composed of 4 polypeptide classes of 27 kDa (C1), 25 kDa (C2), 17 kDa (C4) and 15 kDa (C5) with solubility properties very similar to those of the 22 kDa and 19 kDa alpha-zeins. Like the alpha-zeins, the C1 and C2 alpha-coixins corresponded to 80% of total Coix prolamins. The fraction corresponding to gamma-coixin contained only one protein band of 22 kDa (C3). This coixin fraction has solubility properties similar to those of gamma-zein and represents 15% of the total coixin. The beta-zein fraction was composed of a major 17 kDa protein band, while the beta-coixin fraction consisted of a mixture of alpha- and gamma-coixins. Polyclonal antibodies raised against C1 recognized C1 and C2 and cross-reacted strongly with the 22 kDa alpha-zein, as did C4 and C5 antisera. The antiserum against gamma-coixin showed strong cross-reaction with gamma-zein. The homology between coixins and zeins was further investigated by using Southern hybridization analyses. The genomic DNA of maize and Coix were digested with several restriction enzymes and probed with cDNA clones representing 19 and 22 kDa alpha-zeins as well as the 28 and 16 kDa gamma-zeins. The Coix genome showed complex cross-hybridization sequences with the 22 kDa alpha-zein cDNA, while no cross-hybridization was observed with the 19 kDa cDNA clone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102854 TI - Differential expression of two related organ-specific genes in pea. AB - We have screened a pea genomic library using a cDNA probe derived from pea shoot RNA. From this screen, we isolated two closely related genes, designated as S2 and P4. An intriguing property of these two genes is the presence in their coding region of a repeated sequence that is conserved between them in sequence but not in the number of the repeating units. The predicted amino acid sequence suggests that these proteins could be exported and glycosylated. 3' S1 analysis reveals that one of the genes, S2, is expressed highly in stem, as expected from previous work. However, mRNA derived from the other gene, P4, is not detectable in stem tissue, but is present in tissue derived from pea pods. The 5' upstream sequence of S2 and P4 are 94% identical up to position -121, suggesting that sequences upstream of -121 are responsible for organ-specific expression of the two genes. PMID- 2102853 TI - The apoprotein precursor of the major light-harvesting complex of photosystem II (LHCIIb) is inserted primarily into stromal lamellae and subsequently migrates to the grana. AB - The formation of the lateral distribution of the major antenna complex of photosystem II (LHCIIb) between the granal and stromal lamellae was studied. Specifically, the localization of the insertion and the assembly of the precursor of the apoprotein of LHCIIb (pLHCP) were studied with isolated thylakoids. After insertion of pLHCP into isolated thylakoids, fractionation of the latter into granal and stromal lamellar was performed. At 25 degrees C most of the precursor was located in the granal lamellae, although both highly purified granal and stromal lamellar fractions demonstrated a similar capability to insert pLHCP. When the insertion reaction to the thylakoids was performed at 10 degrees C, followed by their separation into stromal and granal lamellae, the labelled pLHCP was localized in the stromal ones. To examine whether pLHCP inserts into both granal and stromal lamellae, or preferentially into stromal lamellae and subsequently migrating to granal lamellae, a chase experiment was performed. Insertion of pLHCP at 10 degrees C was followed by chase of the radioactive precursor with excess of non-radioactive pLHCP at 25 degrees C. From the results presented it is evident that the level of pLHCP in stromal lamellae was gradually reduced, while it gradually accumulated in the granal lamellae. Furthermore, the pLHCP in the stromal lamellae was found to be in a 'free' form, while after migrating to the granal lamellae it assembled into the pigmented LHCIIb. PMID- 2102855 TI - Alcohol dehydrogenase gene expression in potato following elicitor and stress treatment. AB - A cDNA clone corresponding to a mRNA that rapidly accumulates during the hypersensitive-like response induced by elicitor treatment of potato (Solanum tuberosum L.) tuber was characterized. The clone encodes a polypeptide (Mr = 41,097) having 83%-85% amino acid identity with known plant alcohol dehydrogenase sequences (ADH; EC 1.1.1.1). The identity of the clone was confirmed by measuring the ADH enzyme activity in extracts of Escherichia coli transformed with the cDNA clone. In potato tuber disks, a wide range of stresses, including treatment with fatty acid elicitors, salicylic acid, UV light and anaerobiosis, was shown to induce accumulation of Adh transcripts. In stems, a high constitutive level of Adh transcripts could be detected in 4-week old plants, but not in 8-week old plants. However, the mRNA could be induced to accumulate in stems of 8-week old plants by treatment with arachidonic acid elicitor or by anaerobiosis. Induction in leaves was also obtained during anaerobiosis and after treatment with a Phytophthora infestans mycelial homogenate. PMID- 2102856 TI - The pTiC58 tzs gene promotes high-efficiency root induction by agropine strain 1855 of Agrobacterium rhizogenes. AB - Root induction on flax (Linum usitatissimum L.) cotyledon explants by Agrobacterium rhizogenes strain 1855 is markedly increased by co-inoculation with disarmed A. tumefaciens strain LBA 4404 containing a plasmid carrying the tzs gene of pTiC58. Most of the roots (estimated to be more than 90%) were transformed. This effect is most likely due to the secretion of trans-zeatin by A. tumefaciens stimulating the division of plant cells making them more receptive to transformation by A. rhizogenes, although other explanations are possible. This observation supports the idea that the tzs gene, although not essential for transformation, may promote transformation. An obvious application for genetic engineering experiments involving transformation by A. rhizogenes, is to include a vir-induced tzs gene in the transformation system to help maximize transformation efficiency. PMID- 2102857 TI - The effect of different alleles at the r locus on the synthesis of seed storage proteins in Pisum sativum. AB - Rocket immunoelectrophoresis was used to measure the accumulation of storage proteins in developing cotyledons of two Pisum sativum (pea) genotypes, that were close to isogenic except for the nature of the allele at the r locus. There was a marked decrease in legumin accumulation in the rr (wrinkled-seeded) genotype compared to the RR (round-seeded) genotype. The accumulation of vicilin did not differ greatly between the two genotypes. Pulse-labelling studies indicated that the differences in rates of accumulation of legumin between the rr and RR genotypes were a consequence of differences in rates of protein synthesis. Measurements of relative amounts of specific mRNAs, using cDNA clones as probes, showed lower amounts of legumin mRNA in developing cotyledons of the rr, compared to the RR, genotype. Both vicilin mRNAs and convicilin mRNA, the latter of which shows a similar temporal pattern of expression to those of the major legumin species, are relatively unaffected by the nature of the allele at the r locus. Nuclear run-on transcription experiments indicated no differences in the rate of synthesis of legumin transcripts in the rr and RR near-isolines. The consequences of homozygosity for the r allele on storage protein mRNA levels in vitro may be mimicked by manipulating the sucrose concentration of the culture medium. PMID- 2102858 TI - Codon recognition mechanisms in plant chloroplasts. AB - In chloroplasts, all 61 sense codons are found in chloroplast (cp) DNA sequences coding for proteins. However among the sequenced cp tRNAs or tRNA genes, tRNAs with anticodons complementary to codons CUU/C (Leu), CCU/C (Pro), GCU/C (Ala) and CGC/A/G (Arg) [or CGC/A (Arg) in Marchantia] have not been found. In this paper we show that cp tRNA(Ala)(U*GC) cp tRNA(Pro)(U*GG) and cp tRNA(Arg)(ICG) are able to decode the corresponding four-codon family. In the case of leucine codons CUU/C, we show that 'U:U and U:C wobble' mechanisms can operate to allow the reading of these codons by cp tRNA(Leu)(UAm7G). PMID- 2102859 TI - Transformation and regeneration of the self-incompatible species Nicotiana alata Link & Otto. AB - A transformation and regeneration system has been developed for Nicotiana alata, a plant which is being intensively studied as a model of gametophytic self incompatibility. Plantlets can be regenerated efficiently from seedling hypocotyls. Kanamycin-resistant, transformed plants have been obtained by cocultivation of regenerating hypocotyls with Agrobacterium tumefaciens strain LBA4404 containing a binary vector. The transformation frequency was low with less than 1% of tissue explants regenerating transformed plants. The transformed plants contained from one to three copies of the introduced DNA. In most cases, the kanamycin resistance phenotype was transmitted to the offspring as a normal Mendelian factor. In one unusual case, none of the offspring inherited the kanamycin resistance of the transformed maternal parent. This plant may have been chimeric or the kanamycin resistance gene may have been inactivated. PMID- 2102860 TI - Structure and expression of a gene encoding the large subunit of ribulose-1,5 bisphosphate carboxylase (rbcL) in the colourless euglenoid flagellate Astasia longa. AB - A gene encoding the large subunit of ribulose-1,5-bisphosphate carboxylase (Rubisco) was identified on a circular 73 kb DNA from the colourless euglenoid flagellate Astasia longa. The rbcL gene of Astasia extends over 3968 bp. It is a split gene interrupted by seven introns as compared to nine intervening sequences in the rbcL gene of the phylogenetically related Euglena gracilis. Coding sequences as well as the positions of the introns within this gene are highly conserved in comparison with the Euglena rbcL except that two introns are missing in Astasia. The alignment of the amino acid sequences deduced from the nucleotide sequences of rbcL of Astasia and Euglena shows 82% identical amino acids whereas 15% of the amino acids represent conservative changes. A 1.5 kb transcript of the rbcL gene was revealed by northern blot analysis of Astasia RNA. By immunoblot analysis the gene product of rbcL was detected as a 53 kDa polypeptide. Genes for components of the chloroplast transcriptional and translational systems encoded by chloroplast DNA of plants and green algae are conserved on the 73 kb DNA of Astasia [24, 25, 26]. From our finding that Astasia obviously is capable of synthesizing the Rubisco large subunit one must conclude that these genes are expressed and form functional plastid transcriptional and translational systems. PMID- 2102861 TI - Cloning of cDNA and chromosomal location of genes encoding the three types of subunits of the wheat tetrameric inhibitor of insect alpha-amylase. AB - We have characterized three cDNA clones corresponding to proteins CM1, CM3 and CM16, which represent the three types of subunits of the wheat tetrameric inhibitor of insect alpha-amylases. The deduced amino acid sequences of the mature polypeptides are homologous to those of the dimeric and monomeric alpha amylase inhibitors and of the trypsin inhibitors. The mature polypeptides are preceded by typical signal peptides. Southern blot analysis of appropriate aneuploids, using the cloned cDNAs as probes, has revealed the location of genes for subunits of the CM3 and of the CM16 type within a few kb of each other in chromosomes 4A, 4B and 4D, and those for the CM 1 type of subunit in chromosomes 7A, 7B and 7D. Known subunits of the tetrameric inhibitor corresponding to genes from the B and D genomes have been previously characterized. No proteins of this class have been found to be encoded by the A genome in hexaploid wheat (genomes AA, BB, DD) or in diploid wheats (AA) and no anti alpha-amylase activity has been detected in the latter, so that the A-genome genes must be either silent (pseudogenes) or expressed at a much lower level. PMID- 2102862 TI - Nucleotide sequence of an alcohol dehydrogenase gene in octoploid strawberry (Fragaria x Ananassa Duch). PMID- 2102863 TI - The chloroplast genome of an exsymbiotic Chlorella-like green alga. AB - Chloroplast DNA was isolated and cloned from Chlorella, strain N1a, exsymbiotic with Paramecium bursaria. BamHI, SalI, KpnI and Xho I restriction fragments of the DNA were assembled into a circular map. The genome consists of approximately 120 kbp of DNA, has a G/C content of 38%, and contains only a single copy of the rRNA cistron. The rRNA cistron is small, 5000-8000 bp, and the 16S and 23S gene are separated by less than 2000 bp. PMID- 2102864 TI - Nucleotide sequence of a pathogenesis-related gene of potato. PMID- 2102865 TI - Nucleotide sequence of a cDNA encoding an alpha/beta-type gliadin from hexaploid wheat (Triticum aestivum). PMID- 2102866 TI - Detection of PR-b proteins in tobacco roots infected with Chalara elegans. AB - All previous studies on pathogenesis-related (b) protein (PR-b) induction in tobacco have been carried out on leaves or callus tissue. This paper reports the production of PR-b proteins also in roots of tobacco plants (Nicotiana tabacum cv. Xanthi NC) infected with Chalara elegans. Antiserum against PR-b1 reacted with PR-b1, PR-b2 and PR-b3 and gave the same pattern of reaction as for leaves. Antiserum against PR-b5 revealed the presence of PR-b4, PR-b5 and, very weakly, PR-b6 which have been shown to be beta-1,3 glucanases. Antiserum against PR-b7 reacted with both PR-b7 and PR-b8 which are chitinases. PMID- 2102867 TI - Genetic analysis of forest tree populations: isolation of DNA from spruce and fir apices. AB - A method is described for the isolation of DNA from spruce and fir, starting with 3 to 5 apices (5 mg material). Apices are prepared manually from dormant buds harvested in summer and autumn, which are homogenized in 30 microliters buffer containing 1% SDS. The DNA is extracted with phenol and precipitated with ethanol. Agarose gel electrophoresis and Southern hybridization show that its molecular length is ca. 30-40 kb and that it is readily digested with various restriction enzymes. The method is very fast, it does not need CsCl centrifugation and is therefore suited for the analysis of large numbers of individual trees. Moreover, the buds can be collected all over the year. The yield of the method is up to 30 micrograms of high molecular weight DNA, enough to do several digests and hybridizations. PMID- 2102868 TI - Nucleotide sequence and deduced amino acid sequence of a gene encoding the 23 kDa polypeptide of the oxygen-evolving complex from mustard (Sinapis alba L.). PMID- 2102869 TI - Mitochondrial malate dehydrogenase from watermelon: sequence of cDNA clones and primary structure of the higher-plant precursor protein. AB - The isolation and sequence of a cDNA clone encoding the complete mitochondrial malate dehydrogenase (mMDH) of watermelon cotyledons is presented. Taking advantage of the polymerase chain reaction technology partial cDNA clones from the central part, the 3' part and the 5' part of the mRNA were obtained with oligonucleotides based on directly determined amino acid sequences. Subsequently, two complete cDNA clones for mMDH were synthesized with a sense primer corresponding to the nucleotide sequence of the amino terminal end of pre-mMDH and two antisense primers corresponding to the major alternative adenylation sites found in the mRNA. The amino acid residues for substrate and cofactor binding identified by X-ray crystallography for pig heart cytoplasmic MDH are conserved in the 320 amino acid long mature higher-plant mMDH. A presequence of 27 amino acids is present at the amino terminal end of the precursor protein. PMID- 2102870 TI - The b-32 protein from maize endosperm: characterization of genomic sequences encoding two alternative central domains. AB - As derived from a cDNA clone, the structure of the b-32 protein of Zea mays, a putative regulatory factor of zein expression, has a central acidic region separated by two domains covered by secondary structure motifs. In this work, three b-32 genomic clones were selected from two genomic libraries obtained from the maize inbred lines W64A and A69Y. The nucleotide sequences of the complete coding region of each b-32 gene, as well as long stretches of their 5' and 3' flanking regions, were determined. Introns are not present in the b-32 genomic sequences. Minor variations among the three genes and an earlier reported b-32 cDNA indicates that they constitute a gene family showing a characteristic polymorphism. Such a polymorphism is highly evident in large segments of the upstream regulatory sequences. Interestingly, when compared with cDNA (W64A) or with gene b-32.120 (W64A), the genes b-32.129 (W64A) and b-32.152 (A69Y) show three jumps of the reading frame in the central part of the coding region, resulting in a completely different sequence of the b-32 protein central domain. In all cases, variations in the N- and C-terminal domains account only for microheterogeneity. PMID- 2102871 TI - Structure and evolution of the 4.5-5S rRNA intergenic region in rDNA from rapeseed (Brassica napus) chloroplasts. PMID- 2102872 TI - Tissue-specific expression of a cDNA clone from cell suspension cultures of Lupinus polyphyllus. PMID- 2102873 TI - Isolation and sequence analysis of a chalcone synthase cDNA of Matthiola incana R. Br. (Brassicaceae). AB - A cDNA clone (pcM12) of the chalcone synthase (CHS) of Matthiola incana R. Br. (Brassicaceae) was isolated from a cDNA library, sequenced and analysed. It comprises the complete coding sequence for the CHS and 5' and 3' untranslated regions. The deduced amino acid sequence shows that the Matthiola incana CHS consists of 394 amino acid residues. Comparison with CHS amino acid sequences of other plants indicates more than 82% homology. PMID- 2102874 TI - Organellar DNA replication in Nicotiana tabacum cultured cells. AB - In the diploid vegetative plant cell, the nuclear DNA is present in two copies, whereas the chloroplast and mitochondria genomes are present in a higher and variable copy number. We have studied the replication of the nuclear, chloroplast and mitochondrial DNA in cultured Nicotiana tabacum cells using density and radioactive markers. Essentially all the 10,000 chloroplast genomes in a given cell replicate in one cell cycle as do all the mitochondrial DNA molecules. No measurable level of unreplicated organellar DNA molecules can be detected in these cells. PMID- 2102875 TI - Linear DNA introduced into carrot protoplasts by electroporation undergoes ligation and recircularization. AB - The integrated DNA in stable transformants formed by direct gene transfer often shows complex restriction patterns. One cause of these complex restriction patterns could be the ligation of plasmid fragments prior to their integration. This paper provides evidence for the ligation of plasmid fragments by plant cells. Carrot protoplasts were electroporated in the presence of pCaMVCATM and assayed for chloramphenicol actyltransferase (CAT) activity 24 h later. Linear and supercoiled forms of pCaMVCATM supported similar levels of CAT expression. Surprisingly, digestion of the plasmid at a site between the CaMV 35S promoter and the CAT coding region reduced expression by only 40-50%. Electroporation carried out in the presence of isolated plasmid fragments suggested that this result was due to ligation of the linearized plasmid by the protoplasts. CAT expression was obtained with a mixture of isolated CaMV 35S promoter and the CAT coding region; neither fragment alone supported expression. Further evidence of ligation was provided by electroporation of protoplasts in the presence of a mixture of linearized pGEM and the 1.5-kb Hind III fragment of pCaMVCATM. DNA isolated from nuclei of the protoplasts was used to transform competent cells of Escherichia coli, and colonies were recovered that carried pGEM with Hind III CaMVCAT inserts. Electroporation of protoplasts in the presence of linear and supercoiled pGEM and use of DNA isolated from nuclei to transform E. coli yielded an estimate of the frequency of plasmid ligation. A maximum of only 4% of the input linear DNA was recovered as circular molecules. This result suggests the frequency of ligation is low, but examination of the plasmid DNA in the plant nuclei by electrophoresis indicates extensive degradation of the plasmid and preferential loss of the circular forms. Thus, the ligated plasmids may be converted to the linear form and hence rendered unrecoverable by cloning into E. coli. PMID- 2102876 TI - Heterogeneity and organization of the ribosomal RNA genes of Cucurbita maxima. AB - Thirty-six clones were recovered from Cucurbita maxima genomic DNA which had been enriched for rDNA and cleaved at the unique repeat unit Hind III site. Twenty nine of these, which contain complete rDNA units, were compared to a standard whose intergenic spacer (IGS) nucleotide sequence has been determined. Twenty-one are identical in length and restriction site pattern. Eight which differ from the standard in length do so because of addition or deletion of varying numbers of IGS subrepetitive units of two different classes, with four of the length variants being different in both of these classes. Seven clones were isolated which contain incomplete repeat units, six of which are composites of rDNA and non-rDNA material. They have been cleaved at the unique rDNA Hind III site at one end and at a non-rDNA Hind III site at the other. We consider it most likely that these are derived from the termini of repeat unit tandem arrays, although other explanations are possible. Twelve individual plants of two different cultivars were examined for heterogeneity of IGS length distribution. They all appear to be identical in this regard. PMID- 2102877 TI - The in vivo pattern of firefly luciferase expression in transgenic plants. AB - Expression of the firefly luciferase gene in transgenic plants produces light emission patterns when the plants are supplied with luciferin. We explored whether in in vivo pattern of light emission truly reveals the pattern of luciferase gene expression or whether it reflects other parameters such as the availability of the substrate, luciferin, or the tissue-specific distribution of organelles in which luciferase was localized. The tissue-specific distribution of luciferase activity and the in vivo pattern of light were examined when the luciferase gene was driven by different promoters and when luciferase was was redirected from the peroxisome, where it is normally targeted, to the chloroplast compartment. It was found that the distribution of luciferase activity closely correlated with the tissue-specific pattern of luciferase mRNA. However, the in vivo light pattern appeared to reflect not only tissue-specific distribution of luciferase activity, but also the pattern of luciferin uptake. PMID- 2102879 TI - Variations during leaf development of the relative amounts of two bean (Phaseolus vulgaris) chloroplast tRNAs(Phe) which differ in their minor nucleotide content. AB - Bean (Phaseolus vulgaris cv. Saxa) chloroplasts contain two tRNA(Phe) species, namely tRNA(Phe)1 and tRNA(Phe)2. By sequence determination, we show that tRNA(Phe)2 is identical to the previously sequenced tRNA(Phe)1 except for two undermodified nucleotides. By reversed-phase chromatography analyses, we demonstrate that the relative amounts of these two chloroplast tRNAs(Phe) vary during leaf development: in etiolated leaves the undermodified tRNA(Phe)2 only represents 15% of total chloroplast tRNA(Phe), during development and greening it increases to reach 60% in 8-day-old leaves, and it then decreases to 9% in senescing leaves. PMID- 2102878 TI - Development of a heat shock inducible expression cassette for plants: characterization of parameters for its use in transient expression assays. AB - A heat-inducible expression cassette has been constructed to study the conditional expression of sense or antisense orientations of any sequence of interest in transgenic plants or plant tissues. The construct includes the promoter and all but 5 bases of the mRNA leader from the soybean Gmhsp17.5-E gene, the polylinker from pUC18 (modified to remove the ATG), and a fragment that contains the polyadenylation signal and site from the nopaline synthase gene. Analysis of transient expression of a construct containing the beta-glucuronidase (GUS) coding sequence cloned in the cassette and introduced into Nicotiana plumbaginifolia protoplasts by electroporation shows that the promoter has high expression at heat shock temperatures. This construct is expressed at a roughly 80-fold higher level per unit time than a cauliflower mosaic virus 35S gene promoter-GUS construction. The heat shock promoter is regulated positively by supercoiling in this transient assay system. The level of expression of HS-GUS constructions with the polyadenylation sites from either the nopaline synthase gene or the Gmhsp17.5-E gene was similar. Constructs with a perfect fusion at the 5' end had higher levels of expression than those with the corresponding nonperfect transcriptional fusion. PMID- 2102880 TI - The structure of the large spacer region of the rDNA in Vicia faba and Pisum sativum. AB - The complete nucleotide sequence of the rDNA large spacer region was determined for two related legume plants, Vicia faba and Pisum sativum. In the large spacers of both plants, there were one or several tandem arrays of repeated sequences which account well for the length heterogeneity of the rDNA repeating units. When the entire lengths of Vicia and Pisum rDNA large spacers were compared, significant sequence similarity ranging from approximately 50 to 80% was observed, thus a close phylogenetical relationship was revealed. However, organization patterns of these rDNA spacers were clearly different from each other. The Pisum rDNA large spacer contained only one type of repeated sequence of about 175 bp, whereas the Vicia contained five kinds of repeated sequence. In addition, the initiation site for transcription was tentatively determined by S1 protection experiment. PMID- 2102881 TI - Transcriptional regulation of a patatin-1 gene in potato. AB - Patatin is an abundant glycoprotein in the tubers of potato plants that has a lipid acyl hydrolase activity. Fusions of the promoter of patatin genes that are highly expressed in tubers with the reporter gene encoding beta-glucuronidase (GUS) have shown that patatin transcription has a high degree of tuber specificity. Patatin transcription was also inducible in other organs of transgenic potato by growth on high concentrations of sucrose. Experiments were conducted to define regions of the patatin promoter that confered tuber specific expression and sucrose inducibility. Sequences between -40 and -400 bp and between -400 and -957 bp of the transcriptional start site were able to confer tuber-specific expression on a heterologous truncated promoter. The cell specificity of GUS transcription in the transformants indicated that organ specificity was possibly determined by source-sink relationships of sucrose, or a metabolite of sucrose, in the whole plant. PMID- 2102882 TI - Sequences 5' to the conserved 28 bp Leg box element regulate the expression of pea seed storage protein gene legA. AB - The function of the 28 bp conserved Leg box element found in the 11S legumin-like genes of Vicia, Pisum, Glycine and Helianthus in controlling gene expression has been examined. Transgenic tobacco plants containing 124 bp of 5' legA flanking sequence including the Leg box and all sequences downstream to the start of transcription failed to activate the gene, as judged by ELISA and northern assays. Expression was first detected in a promoter truncation construct which contained 549 bp of 5' flanking sequence. These two promoter truncation constructs were additionally examined for their ability to interact with pea seed nuclear proteins. The use of DNA-protein binding and mobility shift assays showed that the -124 bp fragment which included the Leg box did not bind nuclear proteins. In contrast, nuclear proteins were shown to strongly bind to the -549 bp flanking sequence fragment. The correlation of transgenic plant analysis with DNA binding assays indicates that the highly conserved 28 bp Leg box element is not the sole promoter determinant in legumin gene expression. PMID- 2102883 TI - The non-conserved region of cucumopine-type Agrobacterium rhizogenes T-DNA is responsible for hairy root induction. AB - The T-DNA regions of three strains of Ri plasmids 1855, 8196, 2659 (agropine, mannopine and cucumopine type respectively) share two highly conserved regions flanking a non-homologous central part. We have cloned segments of the cucumopine Ri plasmid 2659 T-DNA in the binary vector system Bin 19 and infected carrot discs with recombinant Agrobacterium strains. We show here that the central non conserved region is crucial in hairy root induction as it is sufficient to induce rooting on the apical (auxin-rich) surface of carrot discs; in order to observe rooting on the basal (auxin-depleted) side of the discs, a longer T-DNA fragment, also encompassing part of the right conserved region, had to be utilized in conjunction with a Agrobacterium strain carrying aux genes. Differences of growth properties in culture are exhibited by roots transformed with different fragments of pRi 2659 T-DNA, although all transformed roots show the plagiotropic behaviour typical of hairy roots. PMID- 2102884 TI - Analysis of promoter activity from an alpha-zein gene 5' flanking sequence in transient expression assays. AB - Three DNA regions required for high levels of transcription were identified by transient gene expression analysis of the 5' flanking region of a 19 kDa alpha zein gene. For these analyses, the zein promoter region was fused to the beta glucuronidase (GUS) gene and assayed by transient expression in carrot protoplasts. A 107-bp sequence (-114/-8) containing the TATA box resulted in low levels of GUS activity. Addition of the proximal 75 bp (-189/-114) doubled the level of GUS expression, and a further increase in expression was obtained when additional upstream sequences (-483/-226) were placed 5' of the zein promoters. Zein upstream sequences enhanced transcription independently of the -189/-114 region. Although the -189/-114 region was not essential for transcription, it was important to obtain maximum GUS activity. A 121 bp upstream sequence (-347/-226) that contains the conserved TGTAAAG sequence gave high levels of GUS activity when placed in either orientation 5' of the zein promoter sequences. However, nucleotides -347 to -309, containing the TGTAAAG sequence, could be deleted from this fragment without a significant change in GUS activity. Zein upstream sequences did not promote transcription of the GUS gene in somatic maize protoplasts. The upstream activating sequence from the cauliflower mosaic virus (CaMV) 35S promoter placed 5' of deletion mutants of the zein promoter also failed to produce GUS activity above background. PMID- 2102886 TI - Nucleotide sequence of the promoter region from kiwifruit actinidin genes. PMID- 2102885 TI - A root acyl carrier protein-II from spinach is also expressed in leaves and seeds. AB - During the synthesis of fatty acids and their utilization in plastids, fatty acyl moieties are linked to acyl carrier protein (ACP). In contrast to previously cloned organ-specific ACP isoforms, we have now isolated a cDNA clone for a potentially constitutive ACP isoform from a spinach root library. Identity between the amino acid sequence encoded by this cDNA and N-terminal sequence data for ACP-II protein from spinach leaf indicates that the root cDNA encodes ACP-II. The deduced amino acid sequence for ACP-II shows 62% identity with spinach leaf ACP-I. Southern analysis suggests that multiple ACP genes or pseudogenes occur in the spinach genome. High-stringency northern blot analysis and RNase protection studies confirm that, within the region encoding the mature ACP-II, the cloned ACP sequence is expressed in leaves and seeds as well as in roots. Quantitative RNase protection data indicate that the ratio of ACP-I and ACP-II mRNA sequences in leaf is similar to the ratio of the two proteins. PMID- 2102887 TI - Sequence divergence of pea Cu/Zn superoxide dismutase II cDNAs. PMID- 2102888 TI - Characterization of the wheat mitochondrial orf25 gene. AB - The wheat mitochondrial orf25 nucleotide sequence of 576 bp has been determined. Its derived protein sequence shares 88% and 75% amino acid identity with those of maize and tobacco mitochondria, respectively. The wheat and tobacco orf25 sequences lack four inserts, of 6 bp to 36 bp, that are present in the maize homologue. The wheat orf25 gene is actively transcribed and is preceded by a regulatory sequence block very similar to those located upstream of the wheat coxII and atp6 genes. Our observations support the view that orf25 sequences encode a functional polypeptide in plant mitochondria. PMID- 2102889 TI - Prevalence of anaemia in the aged population in selected slums of Hubli City. PMID- 2102890 TI - Will the present health check-up system invite yellow fever in India? PMID- 2102891 TI - Biological characteristics of institutional delivery cases in a rural area. PMID- 2102892 TI - Feeding practices of rural infants--a cross sectional study. PMID- 2102894 TI - Problem of zoonotic rabies in India and recent advances in diagnosis. PMID- 2102893 TI - Acquired immunodeficiency syndrome (AIDS) PMID- 2102895 TI - A study of the impact of health education inparted to school children on their knowledge, attitude and practice in regard to personal hygiene. AB - Education concerning prevailing health problems and the method of preventing and controlling them was considered to be one of the first eight essential activities in primary health care. Hence this study was attempted to assess the impact of health education on the knowledge, attitude and practices of school children aged 10-14 years in two secondary schools situated in Burdwan District of West Bengal. For this purpose health education was imparted by a team consisting of Medical Officer and Paramedical staff. Education was given on personnel hygiene. The entire education programme was arranged in such a way that the course could be completed in six months time. The knowledge, attitude and practice status of the students was assessed before imparting training, twice during the training period at an interval of three months and finally after 9 months from the start of training. The evaluation was done with the help of scoring. The results indicated that the health knowledge of the student significantly improved after education. Attitude of the students towards personal hygiene also improved significantly after education. The practice of personal hygiene improved significantly as well. The present study also revealed that the improvement in health practice was not commensurating with the improvement of knowledge and attitude after education. PMID- 2102896 TI - Socio-psychological study of the prostitutes. AB - Only 8 percent of the prostitutes were literate. Income per night varied from Rs 10 to Rs 30 for 72% of the prostitutes. Whereas only one third of the married women were happy with the profession, 95.92% of Devdasis liked the profession. Illiteracy, domestic unhappiness, deception, destitution, poor socio-ecomic status of parents, and religious custom of Devdasi were the important contributory factors for landing innocent girls or socially handicapped women into prostitution. PMID- 2102897 TI - Cervical cytology screening in Calcutta and adjoining areas with special reference to carcinoma of the uterine cervix. AB - A total of 1232 female subjects including 100 prostitutes from Calcutta and adjoining areas in the age group of 21-70 years were screened for cervical pathology according to the method of Papanicolaou. Of 1232 examined, 815 were found to have smears with normal cellular cytology (66.15%). The others were grouped into dysplasia (18.4%) and inflammatory (15.4%) according to the cytomorphological characteristics of the exfoliated cells. The findings though revealed more cases of cervical dysplasia in women with early marriage, early childbirth, high parity and multiple sexual partners, it failed to support the smegma theory of cervical carcinoma. This study also showed a number of inflammatory cervical smears in women coming from low socio-economic group. PMID- 2102898 TI - Bleb formation in the renal epithelial cell line LLC-PK1 exposed to N2-methyl-9 hydroxyellipticinium acetate (celiptium). AB - In this short communication, the authors describe the dose-dependent formation, by the antitumour drug celiptium in vitro, of blebs in pig kidney epithelial cells, illustrating it by scanning electron micrographs. The mechanism of renal injury by celiptium is discussed by a survey of the relevant literature. PMID- 2102899 TI - Protective action of coenzyme A on paracetamol-induced tissue depletion of glutathione. AB - Paracetamol toxicity induced in mice a significant depletion in hepatic and renal glutathione concentrations. The administration of CoA in animals prevents the mortality induced by paracetamol and simultaneously prevents the reduction in renal and hepatic glutathione concentrations. PMID- 2102900 TI - Hyperbaric oxygen- and ethanol-induced infiltration of rat hepatic triglycerides and the protective action of coenzyme A. AB - The ethanol-induced increased synthesis of fatty acids in the liver is enhanced by hyperbaric oxygen exposure. Both lipid peroxidation and glutathione depletion are involved in these hepatic alterations. Coenzyme A can intervene in these mechanisms. The administration of CoA prevents hepatic lipid infiltration and the glutathione reduction induced in the rats by ethanol and hyperbaric oxygen exposure. PMID- 2102901 TI - Alpha 1-antitrypsin variants produced by recombinant DNA: differences in elastase inhibitory activity and resistance to oxidant agents. AB - Inherited or "acquired" deficiency of alpha 1-antitrypsin (believed to be the cause of pulmonary emphysema) will probably be treated in the future by replacement with alpha 1-antitrypsin purified from human plasma or produced by recombinant DNA, which seems promising because it permits site-specific mutagenesis in the oxidizable active site of the normal human alpha 1 antitrypsin. The aim of this in-vitro study was to investigate the elastase inhibitory activity and the resistance to oxidizing agents of normal human alpha 1-antitrypsin, a recombinant yeast-produced variant (VAL 358) and a recombinant E. coli-produced variant (LEU 358). The inhibitors were exposed to chemical oxidants (NCS, H2O2, xanthine/xanthine oxidase, chloramine-T) and to PMA activated neutrophils. The elastase inhibitory activity was assayed on porcine pancreatic elastase and neutrophil elastase. Normal alpha 1-antitrypsin and VAL 358 variant were good inhibitors of both elastases. LEU 358 variant was the best inhibitor for neutrophil elastase, but it poorly inhibited the porcine pancreatic elastase. Normal alpha 1-antitrypsin was affected by all oxidants; both variants were almost totally resistant to chemical oxidants and to activated neutrophils. We conclude that recombinant alpha 1-antitrypsin variants differ in their elastase inhibitory activity and offer increased resistance to oxidant agents. PMID- 2102902 TI - Experimental strategies to explore the molecular details of MHC-peptide complexes. PMID- 2102903 TI - Inhibition of T cell activation by MHC blockade. PMID- 2102904 TI - Bacterial lipopolysaccharides: structure, metabolism and mechanisms of action. AB - Endotoxins (lipopolysaccharides, LPS) are biologically active substances present in the outer membrane of gram-negative bacteria. They induce a spectrum of biological effects which may be harmful or beneficiary for the host. Lipid A is the biologically active part of the LPS molecule. This was demonstrated using soluble forms of lipid A and more recently confirmed further by employing synthetic lipid A. LPS administered into experimental animals circulates as LPS/HDL complex and is cleared from the blood mainly into the liver and spleen. In the liver LPS undergoes partial deacylation however without a loss of toxic activity. Its excretion is effected mainly via the bile into the gut. The lethal toxicity and tolerance inducing properties of LPS are mediated by macrophages through tumor necrosis factor alpha (TNF alpha), which is probably the most important endogenous mediator of the lethal effects of LPS. The lethal toxicity of LPS may be completely inhibited by anti-TNF alpha antibodies. PMID- 2102905 TI - Role of bacterial lipopolysaccharides in the development of natural antibacterial activity mediated by human peripheral blood T lymphocytes. AB - The role of bacterial lipopolysaccharides (LPS) has been evaluated for their influence on the human T cell-mediated anti-Salmonella typhi activity. In nonendemic areas for salmonellosis this activity is exerted by CD4+ lymphocytes armed by IgA, whereas in endemic zones besides these cells also CD8+ lymphocytes armed by IgG display an elevated anti bacterial activity. These results suggest that, in endemic regions, continuous antigenic challenge and, in particular, that exerted by lipid A (the active moiety of LPS) may play a role in triggering this activity. In other series of experiments, pretreatment of endemic peripheral blood lymphocytes (PBL) with smooth and rough (Rb and Re) forms of Salmonella LPS leads to the inhibition of antibacterial activity. In this respect, Re-LPS, which contains lipid A covalently linked to the core-chetodeoxyoctonate, gives rise to the maximum of inhibition. Finally, fractionation of PBL by means of S. minnesota R345 (Rb) cytoadherence has led to the conclusion that anti bacterial activity is present in the Rb-unbound population, thus indicating that bacterial adherence to PBL is a distinct phenomenon from natural anti-S. typhi activity. The overall results suggest that lipid A is able to modulate the expression of antibacterial activity exerted by human peripheral blood T cells. PMID- 2102906 TI - Lipopolysaccharides of oral anaerobes associated with chronic inflammation: chemical and immunomodulating properties. PMID- 2102907 TI - Immunoregulatory confluence: T cells, Fc receptors and cytokines for IgA immune responses. AB - IgA isotype responses are regulated by at least two compartments including those of CD4+ Th2 type cells and cytokines produced by these cells. Interaction of CD4+ Th cells and APC via TCR and Ag-MHC II leads to activation of Th2 type cells. This would allow for secretion of cytokines, especially IL-5 and IL-6 which are key cytokines for the terminal differentiation of B cells into Ig secreting cells. Further, expression of Fc alpha RII on CD4+ Th2 cells could be important for the recruitment of sIgA+ B cells which would allow selective interactions of Th2 cells and sIgA + B cells via Fc alpha RII. This could lead to selectively transfer of IL-5 and IL-6 to sIgA + B cells from CD4+ Th2 cells. PMID- 2102908 TI - Correlation of serum vitamin A and its transport protein (RBP) in malnourished and vitamin A deficient children. AB - Eighty nine children were studied for retinol (vitamin A) estimation and its transport protein--retinol-Binding Protein (RBP). Serum levels of retinol, RBP and serum protein and albumin were found to be low in children with signs of vit. A deficiency irrespective of their nutritional status. Serum levels of retinol and RBP were risen significantly almost double, after the oral and parenteral administration of vitamin A. PEM interferes with hepatic synthesis of RBP and the release of RBP from the liver depends on vitamin A. Vitamin A is a limiting factor, the presence of which is required for the release of apo-RBP from the liver. PMID- 2102909 TI - Counterimmunoelectrophoresis in the immunodiagnosis of amoebiasis. AB - Counterimmunoelectrophoresis (CIE) detection of antiamoebic antibodies in the patients' sera, has been carried out and correlated with the routine diagnostic microscopic examination of stool and pus samples. The clinically suspected amoebiasis cases were divided into two main groups, (i) proved positive for Entamoeba histolytica as detected by microscopic examination of samples, and (ii) negative for the parasite. A total 153 cases of intestinal amoebiasis were studied. CIE was positive in 27 of the 84 proved cases, and in 12 out of 69 unproved cases showing negative microscopy. A total of 59 cases of amoebic liver abscess (ALA) were studied, of which CIE was positive in 20 of the 30 proved cases of ALA and in 4 of the 29 unproved cases. Sera from patients with non amoebic illness (n = 48) gave negative results with CIE. Similarly sera from normal healthy controls (NHC) (n = 100) and asymptomatic cyst passers (n = 75) were negative by CIE. PMID- 2102910 TI - A study of V. cholerae strains isolated in Bombay. AB - Of 935 faecal samples studied over a period of one year, V. cholerae 01 was isolated from 102 samples (10.9%). All the strains were found to be E1 Tor Ogawa. The strains belonging to the phage types 2 and 4 were encountered in our study, type 2 being the highest (76.5%). The sensitivity pattern of all strains to the commonly used antibiotics was determined. Strains sensitive to gentamicin (92.2%), nalidixic acid (85.3%), kanamycin (83.3%), cotrimoxazole (80.4%) and chloramphenicol (75.5%) were observed. Out of the total, 36.3%, 29.4% and 28.4% of V. cholerae strains were found to be resistant to ampicillin, streptomycin and tetracycline respectively. V. cholerae was isolated throughout the year indicating the endemicity of cholera in Bombay. PMID- 2102911 TI - Liver trauma (management in 105 consecutive cases). AB - One hundred and five consecutive patients who sustained liver trauma during the period from Jan 1986 to Dec 1988 are reviewed. Of these, 82 cases suffered from blunt abdominal injury while the rest had penetrating trauma. Simple hepatorrhaphy and use of topical hemostatic agents were the only modes of treatment for 76 cases, hepato-omentorrhaphy was used in 12 cases and hepatotomy with selective vascular ligation and resectional debridement were carried out in remaining 17 cases. Mortality was 36.2% (38/105), 30 patients died of shock in the perioperative period. Uncomplicated recovery occurred in 50 cases. PMID- 2102912 TI - Outcome of teenage pregnancy. AB - Two hundred consecutive cases up to 19 years of age admitted for confinement at The Nowrosjee Wadia Maternity Hospital, Bombay, were studied. Out of these 200 girls, 6 were unmarried, 51 were anaemic, 20 had toxaemia of pregnancy. Six girls (43%) in the age group 15-17 years delivered prematurely as compared to only 26 girls (14%) in the age group of 17-19 years. This difference is statistically significant. Also, only, 4 girls (29%) in the age group of 15-17 years had full term normal delivery as compared to 113 girls (61%) in the age group of 17-19 years signifying that the outcome of pregnancy becomes worst in girls below the age of 17 years. Ten babies (71%) of mothers in the age group of 15-17 years were LBW as compared to 75 babies (44%) of mothers in the age group of 17-19 years signifying that the incidence of LBW babies is inversely proportional to maternal age. Teenage pregnant girls needed more attention for prevention and treatment of preeclampsia eclampsia, anaemia, prematurity and LBW. PMID- 2102913 TI - Serum sialic acid levels in healthy individuals. AB - Serum sialic acid values, estimated by thiobarbituric acid method of Warren as modified by Saifer and Gerstenfeld in 50 normal healthy persons of both sexes are reported. The average values were 68.47 +/- 4.85 mg% and 67.77 +/- 7.87 mg% for males and females respectively and for both sexes the value was 68.12 +/- 6.70 mg%. Age and sex have no influence on sialic acid levels in serum. PMID- 2102914 TI - The nature of bones and joints: a new perspective. AB - In human ontogeny recapitulating phylogeny, bones arrive late on the scene--long after neurogenesis, musculogenesis, organogenesis and so on are over--as islands of ossification in an ocean of collagen. This study confirms this developmental sequence by demonstrating, in cadavers, the rather independent nature of bone, to which nothing--muscle, tendon, ligament or articular cartilage--is attached. Bone is like the air in a tubeless tyre; it gives rigidity and shape to the tyre, and in return takes the shape of the tyre. The tibia, for example, is the bony tissue that is contained in tyre-like casing made of peritibial soft tissues whose inner limit is the periosteum, which continues proximally and distally as capsules of knee/ankle joint, and to which only are the articular cartilages of the knee and ankle attached, being clearly free from the bones. This study also exposes the truer nature of a joint wherein the articular cartilage assumes anatomic and physiologic significance hitherto unthought of. PMID- 2102915 TI - Diagnosis of peripheral arterial occlusive diseases using impedance plethysmography. AB - Impedance plethysmographic observations have been compared with arteriographic findings in 216 patients with peripheral arterial occlusive diseases. Impedance plethysmographic diagnosis in these patients was obtained by Parulkar's method without apriori knowledge of arteriographic diagnosis. But for minor discrepancy in the anatomical location of the block in few patients, impedance plethysmographic observations correlated very well with arteriographic findings. Impedance plethysmographic diagnosis was found to be correct in 312, wrong in 53, false negative in 8 limbs respectively, yielding a sensitivity of 97.5% and specificity of 98.1% of this technique. PMID- 2102916 TI - Impedance plethysmographic observations in thoracic outlet syndrome. AB - Forty patients with symptoms of neuro-vascular compression in the upper extremities were subjected to impedance plethysmographic study using Parulkar's method. Two patients recorded decreased blood flow (BFI) in supine position and were diagnosed as having partial occlusion at subclavian level. Sixteen of the patients recorded decreased BFI on 90 degrees abduction and hyper-abduction. Twelve of these patients had radiological evidence of anomalous cervicle ribs. In remaining four patients extrinsic impression on the subclavian artery due to fibrous deposits was confirmed by arteriography. Remaining 22 patients recorded normal impedance plethysmograms. Impedance plethysmography thus provided a non invasive modality for confirmation of vascular compression in thoracic outlet syndrome. PMID- 2102917 TI - Diagnosis of venous disorders using impedance plethysmography. AB - Impedance plethysmography (IPG) was carried out in one hundred and forty-one patients suspected of venous disorders using Parulkar's method. In these patients occlusive impedance phlebography (OIP) and venography were also carried out using standard procedures. Comparison of IPG and OIP observations with venographic findings revealed sensitivity of these methods to be 65% and 77.7% in the diagnosis of primary varicosity of veins and chronic deep vein thrombosis respectively with a specificity of 85%. Occlusive impedance phlebograms showing unilateral decrease in OIP parameters were observed to be sufficiently diagnostic. IPG observations in 5 patients with arterio-venous malformation were observed to be different from those in patients with deep vein thrombosis. PMID- 2102919 TI - Choledochoduodenal fistula complicating duodenal ulcer disease (a report of 3 cases). AB - Choledochoduodenal fistula complicating duodenal ulcer disease is a rare occurrence. The present paper describes 3 such cases which were incidentally picked up on upper gastro-intestinal (GI) radiographic study and endoscopy done for ulcer like symptoms. The relevant literature is reviewed. PMID- 2102918 TI - Pulse rate, pre-competition tension and performance in 10,000 meter elite runners of both sexes. AB - Five male and 3 female runners who participated in 10,000 meter distance run in South Asian Federation (SAF) Games, 1987 were volunteered for this pilot study. The pulse rate at rest, 1 hour prior to competition and post-run for 30 min at 5 min intervals were recorded. It was observed that the runners who showed less rise of pulse prior to competition, performed better. This might be attributed to less pre-competition tension in them which helped the athletes to perform better. PMID- 2102920 TI - Duodenal obstruction due to appendicular abscess (a case report). AB - The obstruction to the third part of duodenum due to appendicular abscess is reported here. The abscess had tracked behind the mesocolon and obstructed the duodenum. The case was treated by drainage of abscess and anterior gastrojejunostomy. PMID- 2102921 TI - Osteoarticular tuberculosis with involvement of multiple sites (a case report). PMID- 2102922 TI - Malignant melanoma of the nasal cavity (a case report). AB - A case of malignant melanoma of the nasal cavity is reported. The rarity of its occurrence warrants its mention. PMID- 2102923 TI - Surgical management of CSF otorrhoea (a case report). AB - Four cases of CSF otorrhoea following surgery are presented. The etiopathology and its surgical management are discussed. PMID- 2102924 TI - [Modern principles of the surgical treatment of focal lesions in the liver]. PMID- 2102925 TI - [A case of tertiary hyperparathyroidism following kidney transplantation complicated by lithiasis]. AB - For the first time in Bulgaria the authors present a case of tertiary (autonomous) hyperparathyroidism, persisting in a patient who had successful kidney transplantation. Subtotal parathyroidectomy six months after the transplantation led to complete cure. Associated with the underlying disease, a rare complication was also observed in the patient--calculosis in the grafted kidney, spontaneously eliminated 40 days after the parathyroidectomy. PMID- 2102926 TI - [The pseudotumor form of renal tuberculosis]. PMID- 2102927 TI - [An instrument for tunneling and endoprosthesis of the bile ducts in hilar cancer of the liver and biliary tract]. PMID- 2102928 TI - [External drainage of the thoracic duct with and without lymphosorption in the endotoxic phase of phalloid mushroom poisoning]. AB - For the first time in Bulgaria and maybe in the world is reported very good therapeutic effect of the application of external drainage of the thoracic duct with and without lymphosorption in two consecutive cases of phalloid mushroom poisoning. Concrete indications are suggested for application of the method in this type of poisoning - in the late endotoxic phase of the poisoning when all other methods have been used with no effect. PMID- 2102929 TI - [The quantitative assessment of duodenogastric reflux following operations for perforated duodenal ulcers]. AB - Sixty patients operated for perforated duodenal ulcer were examined for the presence of duodenogastric reflux by quantitative estimation of bilirubin in gastric aspirate for a period of 3 to 6 months after the operation. Twenty healthy subjects served as controls. The operated patients were divided in three groups depending on the type of operation: simple suturing, truncus vagotomy with pyloroplasty according to Heinicke-Mikulicz technique and proximal selective vagotomy with rrhaphy (20 patients in each group). It was shown that duodenogastric reflux following proximal selective vagotomy with rrhaphy was almost as common as in the control group. Peak levels of gastric bilirubin were found after truncus vagotomy with pyloroplasty (2.01 +/- 0.51 mmol/l). A practicable method of examination of bilirubin in gastric juice, which can gain acceptance in every hospital laboratory, is suggested. PMID- 2102930 TI - [The treatment of varicose ulcers]. PMID- 2102931 TI - [Our experience with nonanatomical liver resections]. AB - The current status of the problem of nonanatomical liver resections is presented. Some characteristics of the technique applied in them are recorded and the indications for application of the operative technique are specified. Personal five-year experience (1983-1988) with 21 nonanatomical liver resections, applied in gall bladder cancer (4 patients), metastatic tumors (8 patients), high-grade biliary obstruction (7 patients), hemangioma (1 patient) and multiple echinococcosis (1 patient). The early postoperative results were very good, with early postoperative death of one patient. On the basis of these results, the authors advise extension of the indications for application of nonanatomical liver resections. PMID- 2102932 TI - [Subphrenic abscess and suppurative pericarditis as complications in children with perforated appendicitis]. AB - The combination of subphrenic abscess with purulent pericarditis is a rare postoperative complication of perforated appendicitis in children, with severe clinical course, difficult to diagnose and high case fatality rate. A 7-year-old child with this complication, successfully diagnosed and treated is reported. The importance of complex therapy--surgical and intensive and collaboration between pediatric surgeons, anesthesiologists, cardiac surgeons and cardiologists for the favourable outcome is emphasized. PMID- 2102933 TI - [Primary tumors of the stomach in childhood]. AB - Two cases of primary tumors of the stomach in children (7 and 10 years of age) are reported. One of them had non-Hodgkin's lymphoma and the other hamartoma, both radically operated. In the former case subtotal resection of the stomach was made followed by polychemotherapy. For an observation period of one year there was no evidence of recurrence or metastases of the neoplastic process. The incidence, histologic characteristics, clinical course, diagnostic and therapeutic problems in tumors of the stomach in children, with special reference to non-Hodgkin's lymphoma and hamartoma, are discussed. PMID- 2102934 TI - [Antithrombin III deficiency as a cause of unexplained thrombosis recurrences in vascular surgery]. AB - Antithrombin deficit may be a cause of spontaneous vascular thrombosis or rethrombosis, following vascular operations, which remain inexplicable to clinicians. Three cases are reported of A III deficit, in two of whom vascular rethrombosis resulted from considerable fall in A III activity, measured by kinetic method and in the third patient this severe postoperative complication was averted. The importance of measuring A III in patients with arterial insufficiency in whom vascular reconstruction is forthcoming is discussed. The substituting therapy in patients with this pathology and arterial reconstruction is given due consideration. Substituting therapy is recommended as means for avoiding rethrombosis in patients with proven A III deficit, as well as a method of treatment, together with heparin therapy, after successful reoperation of such patients. PMID- 2102935 TI - [Endorectal ultrasonic study of the large intestine (a preliminary report)]. AB - Endorectal ultrasound examination is known mainly as a method of examination of the prostate gland. In this report results are presented of the use of this method in patients with tumors of the rectum or of the adjacent organs, with the purpose of evaluating the relation of the tumor to the intestinal wall. In 7 cases gamma 4 with cancer of the colon and 1 with benign tumor, 1 patient with cancer of the uterine cervix and 1 patient with recurrent tumor in the pararectal space) the results of endorectal ultrasound examination matched the data of the histopathologic examination (in 6 cases) and with the clinical course of the disease (in 1 case) followed up over a period of 5 years. It is suggested that endorectal echography has a place as supplementary method of examination in patients with malignant tumors in the rectal area; the accumulated information will help to choose the therapeutic approach. PMID- 2102936 TI - [The diagnosis and surgical treatment of teratogenic tumors of the mediastinum in childhood]. AB - Mediastinal tumors are leading tumors in pediatric chest oncology. Teratogenic mediastinal tumors are characteristic of early childhood. For a period of 7 years 4 children with teratogenic tumors of the mediastinum--7.8 per cent of all mediastinal tumors--have been diagnosed at the Department of Pediatric Surgery, thoracic unit. The authors analyse the clinical symptoms, the tools of diagnosis, emphasizing the diagnostic importance of computer tomography, echography and angiocardiography. All children were operated (total extirpation of the tumor). Three children had benign teratoma, 1 mature teratoma including malignant elements (ECT)). All children were in good state of well-being; in one of them chemo- and radiotherapy is still in progress. PMID- 2102937 TI - [Pleuropulmonary surgical complications in children with abdominal surgical diseases]. AB - In a series of 4350 children with abdominal surgical diseases operated at the Department of Pediatric Surgery in Sofia for a period of 3 years (1987-1989) the authors have observed 4 cases of pleuropulmonary complications (0.09 per cent). In two of these children the primary abdominal operation was for liver echinococcus, in 1--rupture of the liver and subphrenic abscess and in 1- perforative appendicitis and purulent peritonitis. Symptoms of respiratory failure developed in addition to the abdominal symptoms. Leading in the complex treatment was sanation of the abdominal cavity from the purulent process and double pleural drainage. The severe pathologic changes in the organs of the two adjacent cavities were responsible for the high case fatality rate (25 per cent). PMID- 2102938 TI - [Pharmacokinetic methods for achieving and maintaining stationary plasma levels in the venous administration of drugs]. AB - Proceeding from extensive review of the available literature, the authors discuss the possibilities which pharmacokinetic modelling offers for achieving precise dosage of intravenously administered drugs. Problems associated with the development of pharmacokinetic models depending on the distributive characteristics of the drugs in the body and the desired plasma concentration are principally discussed. Concrete examples for attaining and maintaining stationary plasma concentrations of some intravenously administered drugs in anesthesiologic practice and intensive treatment are indicated. PMID- 2102939 TI - [The drug prevention of thrombotic complications of the vascular approach- arteriovenous fistulae and synthetic prostheses in patients on hemodialysis with antistenocardin]. PMID- 2102940 TI - [Appendicitis in old age]. AB - Proceeding from the results of histomorphologic examination of the appendix in senile age, an attempt is made to explain why the incidence of appendicitis in this age decreases. It was found that in senile age there occur involutive changes which lead to a decline in appendix reactivity and absence of potential possibility for appendicitis to occur. However seldom, the process of senile involution of the appendix may be retarded. In this case the lymph follicles in the appendix contain a germinative center, indicating preserved reactivity and potential possibility for inflammatory process to develop. Senile involution is an overall biological phenomenon, which refers not only to the appendix, but to all other lymph tissue in the body. PMID- 2102941 TI - [The pneumodynamic barium x-ray study of small intestine adhesions (a preliminary report)]. AB - Small-intestinal adhesions are not very rare, but on conventional X-ray examination are frequently missed because of their poor semiotics. By the method of pneumodynamic-barium X-ray examination, which allows to obtain high-quality double-contrast image, in addition to the better visualized classical symptoms- exostotic rebounds, diverticulum-like deformities, peristaltic spasms, spastic contractions etc, one may evince also the following new criteria: when inflated the intestines do not freely increase their volume, as is normal, are not unplaited along the entire abdomen, but remain amassed in a definite zone (usually in the left half); On external pressure the inflated loops do not move, as do the ones without adhesions, but remain fixed, so that their structure remains unchanged. The intestinal loops are crooked with acute angles; when in a normally inflated state, they are not crooked, but long. A frequent finding in small intestinal adhesions are the V-shaped figures in whose bottom there is barium meal over which air passes. A study of the small-intestinal cannon contraction reveals insufficiency in the hydrodynamics of the intestinal passage, marked by delayed evacuation, in spite of the strong peristalsis. This method allows a more precise elucidation than the conventional X-ray examination of the abdominal status in small-intestinal adhesions and better orientates the surgeon to choose conservative or operative treatment. PMID- 2102942 TI - [Internal biliary fistulae (the clinical picture, diagnosis and treatment)]. PMID- 2102943 TI - [Atypical anatomical variants and anomalies of the biliary tract in patients with biliary tract and pancreatic diseases. I. The incidence according to ERCP]. AB - Of 570 patients with clinical manifestations of bile duct and pancreas diseases, examined by ERCP, 122 had different atypical anatomical variants (142 in 114 patients) and anomalies of the biliary passages (8 patients). The incidence of the individual atypical anatomical variants of the bile ducts was, as follows: 1. variants in the entry of the common bile duct in the duodenum--3.3 per cent (19 of 570 patients); 2. variants in the entry of ductus cysticus in the common bile duct--11.1 per cent (63 of 570 patients); 3. variants of the ramifications of the hepatic canals--10.5 per cent (60 of 570 patients). Of the bile duct anomalies, choledochocele was the most common--in 5 of the 8 patients in this group. In addition, there was a double gall bladder, gall bladder atresia and cysts of the intrahepatic bile ducts in one case each. High was the incidence of choledocholithiasis (63 per cent) and especially of primarily formed calculi in the common bile duct (20 per cent), as well as bile duct cancer (11 per cent). Cancer of the biliary passages was significantly commoner in atypical anatomical variants of ductus hepaticus (18 per cent) vs. 8 per cent in atypical variants of ductus cysticus and none in the common bile duct variants (chi 2 = 4.06; p less than 0.05). Cancer of the common bile duct was found also in 1 of the eight patients with anomalies of the biliary passages. PMID- 2102944 TI - [Metastatic tumors of the liver]. PMID- 2102945 TI - [Secondary postresection enteral insufficiency]. AB - The literature on the problem of enteral insufficiency is reviewed. Secondary enteral insufficiency is of interest both to clinicians and to physiologists and pathophysiologists, who might join their efforts for studying the fine mechanisms of the intestinal functions and refine the methods of treatment of enteral insufficiency. PMID- 2102946 TI - [A case of splenic echinococcosis presenting diagnostic interest]. PMID- 2102947 TI - [Malignant lymphoblastic lymphoma of the small intestine]. PMID- 2102948 TI - [Combined echinococcosis and tuberculosis of the liver]. PMID- 2102950 TI - [Personal observations on using artificial anterior chamber lenses]. AB - The analysis concerned 100 eyes (91 persons) operated for senile (89 eyes), traumatic (7 eyes) and pathological (4 cases) cataracts, with implantation of an artificial anterior chamber lens. The age of the patients oscillated between 32 and 86 years. The period of observation amounted from several months to 3 years. In 83 cases the final visual acuity was over 0.7. The authors stated a dependence of the visual acuity on the coexisting general diseases and on the type of cataract. PMID- 2102949 TI - [Comparison of extracapsular cataract extraction with implantation of the artificial lens into the posterior chamber and intracapsular cataract extraction with implantation of the artificial lens into the anterior chamber]. AB - Advantages and disadvantages of both methods are presented on the basis of comparison of 1200 cases of intracapsular cataract extraction with anterior chamber lens implantation and 600 cases of extracapsular cataract extraction with implantation of posterior chamber lens. One has to state that in general the preferential method of extracapsular cataract extraction with posterior lens implantation is connected with several complications. The main disadvantage of intracapsular cataract extraction with anterior chamber implantation is--in 66 p.c.--deformation of the pupil. From our point of view this is a problem of cosmetic nature. On the basis of comparison of disadvantages and advantages we are of opinion that both methods are equally suitable for a broad clinical use. PMID- 2102951 TI - [Effect of preoperative intraocular pressure on the course of cataract extraction]. AB - The connection between the values of the intraocular pressure before cataract surgery and the number of intraoperative complications was checked. It was established that the preoperative hypotony improves in an essential manner the operative conditions and influences favourably the decrease of the number of complications in the course the surgery. It was confirmed that the manual massage of the eye is equally efficient and less influencing generally the patient than the pharmaceutical lowering of the IOP. PMID- 2102952 TI - [Intraocular pressure after cataract extraction with implantation of an intraocular lens]. AB - The subject of our investigations was the behaviour of the IOP after extracapsular and intracapsular operations with implantation of artificial lenses as well into the anterior as into posterior chamber. The investigations were performed on the material of 395 eyes operated in the years 1985-1988. It was established that after these operations glaucoma is a very rare complication. PMID- 2102953 TI - [Intraocular pressure after cataract extraction with implantation of intraocular lenses]. AB - The IOP was measured in large groups of patients with an implanted posterior chamber lens with or without the use of natrium hyaluronate. It was established that implantation of an artificial lens alone does not influence the value of the intraocular pressure. In cases when natrium hyaluronate was used the pressure was slightly higher but only exceptionally it exceeded 35 mm Hg (most frequently in persons with glaucoma existing before the cataract extraction). The IOP was controlled in the course of several days in all the patients without any harmful consequences for the visual function. PMID- 2102955 TI - [Comparison of the methods of wound closure after implantation of intraocular lenses in our modification]. AB - The author applied several methods of closing the operative wound using an incision at the limbus, corneal incision, an incision with a conjunctival or scleral flap and using various stitches. Recently he executes a modified scleral incision cutting off the conjunctiva from the corneal limbus; he considers it convenient and safe. The methods were compared on the basis of 76 cases. PMID- 2102954 TI - [Implantation of intraocular lenses in children]. AB - Implantation of intraocular lenses in children was performed in 42 cases in our department. In 26 children it concerned primary implants, in 16 secondary implants. No major postoperative complications were observed in the period between the 6th and the 24th month after surgery. The visual acuity of 0.5 or better showed 70 p.c. of children after the primary and 66 p.c. after secondary implants. PMID- 2102956 TI - [Intraocular intracapsular lens--our model]. PMID- 2102957 TI - [A method of implantation of intraocular intracapsular disc-shaped lenses]. AB - Presented are the surgical techniques used in implantation of intraocular intracapsular disc-shaped lenses. Particular stages of the operation are photographically documented. The authors present the most frequently encountered complications which appeared in their material and they point out their causes. PMID- 2102958 TI - [Use of neodymium-YAG laser in cataract extraction]. AB - Observations of 45 procedures in 35 patients before and after cataract surgery suggest, that the application of Nd-YAG laser is an effective and safe method of treatment. The most frequent procedures were posterior capsulotomy, iridotomy, vitreotomy, membranotomy, anterior and posterior synechotomy and decission of secondary cataract. Possible complications include intraocular pressure elevations, damage of artificial lenses and hemorrhages from iris vessels. PMID- 2102959 TI - [Extracapsular extraction of hard cataract with simultaneous implantation of intraocular lens and anti-glaucoma operation]. AB - The authors present 7 cases of extracapsular hard cataract extraction with implantation of posterior chamber lens or an intracapsular disc-shaped lens. Because of existing indications they performed simultaneously an anti-glaucoma operation. In all the cases the postoperative IOP persisted in normal limits without any necessity of application of a pharmacological treatment. PMID- 2102960 TI - [Late complications in patients with intraocular lenses]. AB - Examinations were carried out in 222 patients operated for cataract with simultaneous implantation of an intraocular lens. The period of time since the operation amounted 6 to 24 months. The authors observed only minor postoperative complications such as: distortion of the pupil (in 10.8 p.c. of patients), opacification of the posterior lens capsule (2.2 p.c.), a negligible reaction of the iris at the point of contact with the haptic part of the anterior chamber lens (1.4 p.c.), rotation of the lens correctly positioned in the visual axis (0.9 p.c.), incarceration of the haptic part of the anterior chamber lens in the limbal wound (0.9 p.c.), posterior synechiae (0.9 p.c.), occlusion of the pupil by pigment deposits (0.9 p.c.), leakiness of the limbal wound with filtration bleb (0.5 p.c.) and dispersed small deposits of pigment on the anterior surface of the artificial lens. Another complications in the examined patients, known from the literature, were not observed. PMID- 2102961 TI - [Fluorescein angiography of the iris in pseudophakia]. AB - Investigations were performed in a group of 16 patients after cataract extraction with implantation of an intraocular artificial lens. The authors evaluated the condition of the iris on the basis of a biomicroscopic examination and fluorescein angiography up to 1 year after surgery. PMID- 2102962 TI - [Measurement of the power of artificial intraocular lenses]. AB - Fifty five anterior chamber artificial lenses of the Hellgrebe model 2(35) and Fiodorov's (20) were verified from the angle of the power quoted by the producer. The measurement of the length of the frontal power were performed by means of a measurer 70 (Carl Zeiss, Jena, GDR) and by a specially designed plastic cuvette suitable for sterilization. The mean deviation amounted -1.42 dptr. for the Hellgrebe's 2 lens and 0.23 dptr. for Fiodorov's lens. The Hellgrebe type 2 lenses do not answer the international quality norms of tolerance +/- 0.25 dptr. PMID- 2102963 TI - [Comparison of the effectiveness of bupivacaine with xylocaine and xylocaine alone used for akinesia and retrobulbar anesthesia in cataract surgery]. AB - The paper presents a comparison of the efficacy of Bupivacaine with Xylocaine and Xylocaine alone used for retrobulbar injection and akinesia in cataract surgery. Two groups comprising 50 patients each were subjected to evaluation. The results obtained encourage to put into practice the mixture of Bupivacaine with Xylocaine for local anaesthesia in cataract operations. PMID- 2102964 TI - A dBASE III system for managing 35 mm slides in pathology. AB - We describe the design and management of a 35 mm slide database using a menu driven dBASE III PLUS programme and a microcomputer in a large department of pathology that also caters for the individual pathologist. Existing systems described in the literature are geared towards slides of general medicine and do not address the needs of the individual pathologist. A total of 11,481 slides in the Department of Pathology, Faculty of Medicine, University of Malaya, were filed into a single database with each record representing one slide. Nine fields which comprised the slide accession number, reference number, slide category, SNOMED codes, and a description of the slide in natural language, seemed adequate for slide definition. The menu-driven programme had functions which included the abilities to add, delete, edit and back-up records, and to search for desired slides. Although slides may be searched for in various fields, we found that searches using natural language alone were both comprehensive and efficient, provided a standard format of description was adhered to and data entries scrutinized carefully for errors. We believe therefore, that for the pathologist working alone, coded language fields are not absolutely necessary, as manual coding and additional data entry can be time consuming. As expected, for databases larger than 10,000 slides, a 80286 microprocessor-based microcomputer was more efficient. We are of the opinion that a system such as ours is very useful for a large department of pathology or the individual pathologist to file and retrieve 35 mm slides. PMID- 2102965 TI - Phage typing of methicillin-resistant Staphylococcus aureus. AB - 448 isolates of methicillin-resistant Staphylococcus aureus (MRSA) from clinical specimens of patients from the University Hospital, Kuala Lumpur, were phage typed. These included 35 strains causing two separate outbreaks of infection, one in surgical Ward 6B and another in the Special Care Nursery (SCN). Antibiograms of these outbreak strains in Ward 6B and SCN were entirely different. Phage typing revealed that 72% of the MRSA isolates were typable. They were typed entirely by Group III phages, the majority (76%) of which were phage type 85. There was only one isolate in SCN which was typed by Group I (phage 80) and Group III phages. None were typed by phages 94, 95, 96 and Group II phages. 14.6% of the typable isolates gave the long pattern reaction of the phage 6/47/54/75/77/83A/84/85 complex. The majority of the outbreak strains in Ward 6B were of phage type 85, whereas those in the SCN were all of the 6/47/54/75/77/83A/84 phage pattern with the exception of one isolate which was also typed by phage 80, a Group I phage. PMID- 2102966 TI - Age at diagnosis of chronic myeloid leukaemia. PMID- 2102967 TI - The polymerase chain reaction and its role in pathology. PMID- 2102968 TI - The spectrum of lymphoma in Malaysia: a histopathological study utilizing immunophenotyping. AB - A retrospective study was made to determine relative incidence of lymphoma subtypes in Malaysia. High grade non-Hodgkin's lymphoma was found to be common. Low grade non-Hodgkin's lymphoma and Hodgkin's disease were relatively rare in this Malaysian series. Non-Hodgkin's lymphoma of B-cell immunophenotype was four times as common as that of T-cell lineage. There was a high incidence of primary extranodal non-Hodgkin's lymphoma. PMID- 2102969 TI - Detection of Helicobacter pylori from endoscopic biopsies and the biochemical characteristics of these isolates. AB - Helicobacter pylori (formerly Campylobacter pylori) has been recently described as a gastritis-associated bacterium. We examined endoscopic biopsies of 100 patients with dyspepsia and found H. pylori in the gastric antrum of 34 (34%) by either culture, urease tests and/or histology. Thirty-one out of 41 patients (75.6%) confirmed to have chronic active gastritis histologically had H. pylori in their gastric antrum compared to 3 out of 59 patients (5.1%) with dyspepsia but normal histology (p less than 0.01). Histological examination, using gram stain and the Warthin-Starry Silver stain, detected 29 of the 34 positive cases (85.3%); urease test, 26 cases (76.5%) and culture, 22 cases (64.7%). A combination of histological examination and urease test increased the detection rate to 97.1%. Therefore we felt that for the detection of H. pylori in endoscopic biopsies, culture, which is time consuming and expensive, is not necessary in routine diagnosis as it did not improve the diagnostic rate over a combination of histology and urease test. A comparative study on three media (blood agar, chocolate agar and Skirrow's agar) used in the isolation of the organism showed that non-selective blood agar and chocolate agar were superior to Skirrow's agar. The strains isolated appeared to be homogeneous in their morphological and biochemical characteristics. PMID- 2102970 TI - Diagnosis of chronic pancreatitis and pancreatic cancer at the centre of gastroenterology. AB - The installment of 4-step diagnostic system led to an improvement of the final diagnosis of chronic pancreatitis and pancreatic cancer. The average time during which pancreatic cancer proceeds from the onset of symptoms to computed tomography or laparotomy shortened considerably due to the application of the system screening procedures as well as of modern imaging techniques. PMID- 2102971 TI - Risk of gastroduodenal ulcer in gastritis. AB - The present evidence suggests that chronic gastritis is strongly associated with peptic ulcer disease. Gastritis, particularly in antrum, is nearly invariably present in patients with peptic ulcer. Gastritis is a progressive disease which begins as a superficial inflammation and progresses to atrophic gastritis. Gastritis can be considered to lower resistance of the gastric mucous membrane but it may also affect secretion of acid and pepsins from oxyntic mucosa. The presence or absence of gastritis, and its involvement in antral and/or body mucosa, can be considered to reflect the risk and probability of a person to contract peptic ulcer. Estimations of the risks of coexistent peptic ulcer in different types and grades of gastritis suggest that the relative risk (RR) of coexistent peptic ulcer disease is markedly increased in the presence of gastritis in general (RR = 7-10), as compared to patients who have a normal, non gastritic stomach (RR = 1). This risk is particularly high in patients with gastritis of B type (atrophic gastritis is in antrum but body mucosa is non atrophic) in whom the coexistent peptic ulcer is 20-30 times more common (RR = 20 30) than in patients who have normal stomach. On the other hand, the risk of peptic ulcer disease is low in patients who show marked atrophic alterations in the gastric body mucosa (A or AB types of gastritis), the risk being in these patients even lower (RR below 1) than that in patients with normal, non-gastritic stomach. PMID- 2102972 TI - Nutrition and development of gastric cancer. AB - Gastric cancerogenesis is a multistage process. Dietary studies may contribute to elucidation of that complex problem. PMID- 2102973 TI - Value of bile acid determination for the diagnosis of neonatal jaundice. AB - Serum concentrations of bile acids and bilirubin, and activity of alanine transferase and alkaline phosphatase as well as bile acid and bilirubin levels in duodenal contents were determined in 90 infants aged 1-44 weeks (including 49 under 10 weeks of age) admitted to hospital for prolonged jaundice. Infants with extrahepatic cholestasis were found to have statistically higher serum bile acid and bilirubin concentrations. Oral administration of cholestyramine produced a statistically significant decrease in serum bile acids and bilirubin in infants with intrahepatic cholestasis under 10 weeks of age. In 24 out of the 30 infants with biliary tract obstruction total absence of bile acids in the duodenal contents was demonstrated while in the others the concentration did not exceed 0.2 mmol/l. The mean bile acid concentration in infants with intrahepatic cholestasis was 2.81 mmol/l while in 8 infants out of the 60 bile acids were either absent or present in trace amounts. The method had an 84.4% sensitivity. PMID- 2102974 TI - Recent advances in the pathogenesis and treatment of alcoholic liver disease. AB - This paper reviews the recent advances in the pathogenesis and drug therapy of alcoholic liver disease (ALD). Plans for long-term management of patients with ALD have been outlined. No specific drug is available for treating alcoholic cirrhosis at present. As there are no genetic, immunological or biochemical markers to predict the progression of alcohol-induced hepatopathy to date, perivenular sclerosis is the only available hepato-histological marker for developing alcoholic cirrhosis. Total abstinence from drinking alcohol is the primary aim of management. It is also suggested that periodic assessment of synthetic capability of liver might offer warning signal for the deterioration of hepatic lesion in patients with alcoholic cirrhosis. PMID- 2102975 TI - Distribution of serum gastrin in different forms of gastritis among Estonian population. AB - Gastrin level was measured in frozen serum samples of 215 adult Estonians, who took part in a representative population study in 1979, and were followed-up in 1985. Gastric morphology was verified by multiple biopsy specimens from the fundal and antral parts of the stomach, obtained at direct-vision gastroscopy. Certain combinations of antral-body mucosa were revealed which have, and which do not have a significant influence on the fasting gastrin levels. Low values might be observed in subjects having severe atrophic gastritis simultaneously in fundal as well as in antral area. However, in others low concentration of gastrin was seen without any (or without severe) changes of the mucosa. Therefore different factors as duodenal gastrin-producing cells, several molecular forms of gastrin, age of the person seems to contribute to the total serum gastrin level besides the gastric mucosa. High values of gastrin are characteristic to normal antral mucosa accompanied by moderate or severe fundal gastritis. PMID- 2102976 TI - Natural history of peptic ulcer disease in Poland. V. The process of diagnosis of peptic ulcer disease. AB - The analysis of the process of diagnosis establishing in peptic ulcer disease in 5813 patients showed that almost all patient had been subjected to radiological examination of the upper digestive tract (99.5%). Endoscopic examination was done in 57.75% of patients, and histological examination of mucosa was performed in 13.28% of them. The secretory activity of the stomach was studied in 61.48% of cases. Moreover, it was found that nearly half the studied patients (43.23%) came to the doctors after more than 6 months from the onset of the first symptoms, and the diagnosis of the disease was established within 2 months after the first visit to the doctor in 58.48% of cases. PMID- 2102977 TI - Natural history of peptic ulcer disease in Poland. VI. Treatment process in peptic ulcer disease. AB - The analysis of the treatment process in peptic ulcer disease based on the informative databank "Ulcer" used the numbers of outpatients and inpatients treated by conservative or surgical methods. Data are presented also concerning the number and total times of transient working disability due to peptic ulcer, and the effect of treatment by one physician or by several physicians on the treatment process. PMID- 2102978 TI - Gastric acid, gastrin and pancreatic polypeptide responses to modified sham feeding in duodenal ulcer patients before and after highly selective or truncal vagotomy. AB - Gastric acid secretion, as well as gastrin and pancreatic peptide release into the bloodstream before and after TV or HSV were observed in 28 patients following modified sham feeding (MSF) and pentagastrin tests. Prior to surgery the majority of patients showed stimulation of gastric acid secretion and hormone release into the bloodstream as the result of the employed tests. The MSF-induced acid output (SAO) and pentagastrin-induced acid output (PAOpg) values were mainly observed immediately following the stimulus. In the majority of patients MSF triggered an increase in blood gastrin and PP concentrations. Nevertheless, the peak concentration values for the two hormones occurred at different time intervals following the stimulus. For gastrin the peak values appeared later than SAO, whereas for PP they occurred either in the course of or immediately after MSF. Irrespectively of, the type of surgical procedure used and the completeness of vagotomy, the values of BAO, PAO, SAO and PAOpg were significantly lower following the procedure. Blood hormone concentration, however, showed greater variations. The test stimulated gastrin release showed the peak values were greater after, than prior to, the surgery, whereas PP release was markedly inhibited. No correlation was found between gastric acid secretion, blood serum gastrin and PP levels. PMID- 2102979 TI - Prolactin action in cystic fibrosis. AB - The pathophysiology of cystic fibrosis (CF), the secretory properties of CF cells and conductance studies of CF cells and membranes suggest that the basic defect of CF is an abnormality of regulation affecting a broad spectrum of functions. Prolactin (PRL) was proposed as the putative regulatory factor, because the multifarious activities of PRL, especially the well documented osmo- and electrolyte regulatory effects, can be related to all of the symptoms of CF. These include salt loss in sweat, abnormal mucus production, impaired intestinal digestion and absorption, male infertility, delayed puberty, failure to thrive, etc. Additionally those tissues in lower vertebrates in which PRL activity has been demonstrated are phylogenetically related to many of the tissues affected in CF. PMID- 2102980 TI - Pneumatosis cystoides intestinalis: case reports and review of the literature. AB - Pneumatosis cystoides intestinalis is an uncommon condition in which submucosal or subserosal gas cysts are found in the wall of the small or large bowel. Many different causes of pneumatosis cystoides intestinalis have been proposed, including mechanical and bacterial causes. Approximately 85% of cases are thought to be secondary to coexisting disorders of the gastrointestinal tract or the respiratory system. Since 1986 we have observed 4 cases of pneumatosis cystoides intestinalis. A review of the literature is presented with emphasis on the etiology, diagnosis, differential diagnosis, and therapy of pneumatosis cystoides intestinalis. Symptoms of pneumatosis cystoides intestinalis include diarrhea, constipation, rectal bleeding, passage of mucus per rectum, vague abdominal discomfort, abdominal pain, urgency, malabsorption, weight loss, and excessive flatus. Depending on the location of the gas filled cysts the range of symptoms in each patient may vary enormously. PMID- 2102981 TI - Studies on the regeneration of rat intestinal epithelium after exposure to cyclophosphamide. AB - Cyclophosphamide caused changes in Paneth cells. The relationship of these changes to the proliferative reaction of the intestinal epithelium requires a more complete knowledge of various physiological functions of Paneth cells. PMID- 2102982 TI - Organ porphyrins and uroporphyrinogen decarboxylase activity in a case of non functioning adrenocortical carcinoma. AB - In a case of metastasizing hormonally non-functioning carcinoma of the cortex of the left adrenal, leading to the death of a man aged 42, the activity of uroporphyrinogen decarboxylase and the concentrations of tissue porphyrins were determined. In the carcinoma a quantitative rise was observed of uroporphyrin, coproporphyrin and, particularly, protoporphyrin, while the total concentration of these three porphyrins was increased in the bone marrow fourfold, in the kidney eightfold in relation to the primary tumour. The correlation between the reduced activity of uroporphyrinogen decarboxylase and the increased concentration of uroporphyrin was noted in the adrenocortical carcinoma and its metastases to the liver and lymph node, and also in the bone marrow and renal medulla. PMID- 2102983 TI - Management of sporadic gastrinomas. AB - Experiences with medical and surgical treatment modalities in 13 patients with a sporadic ZES, followed up for 1-16 yrs., are presented. Gastric hypersecretion can effectively be controlled by H2-blockers or Omeprazol. Insufficiently adjusted drug dose and drug effect escape are the main reasons of complications from insufficiently suppressed gastric hypersecretion. A tumor-like lesion could be detected by angiography in 8 and by CT scanning in 6 out of 9 patients, US was of no use in detecting solitary adenomas. 8 patients underwent surgery for tumor resection, 4 could be cured definitely with a non-metastatic primary adenoma in the pancreas (2), the liver (1) and a peripancreatic lymphnode (1). Gastrin producing endocrine tumors as the cause of an unusually virulent ulcer disease due to excessive gastric hypersecretion were first described by Zollinger and Ellison nearly 30 years ago. Albeit rare, they deserve our special attentiveness because they pose specific therapeutic problems unknown in common peptic ulcers and other kinds of tumors. Because the patients are, above all, endangered by their ulcer complications, management of patients with Zollinger-Ellison-Syndrome (ZES) has to aim first and foremost at eliminating the excessive gastric hypersecretion and only secondly at removing the hormonproducing tumor. Management of patients along these guidelines has changed decisively during the last years: Previously, elimination of gastric hypersecretion was only achieved by total gastrectomy, whereas now gastric acid excess can effectively be controlled by antisecretory drugs. More over, being no longer under deadline pressure by ulcer complications and having improved imaging techniques at our disposal search for gastrinomas has become more successful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2102984 TI - Does feedback regulation of pancreatic enzyme secretion by duodenal trypsin exist in cholecystectomized patients? AB - Recent studies have supported the existence of a feedback regulation of pancreatic enzyme secretion in man. The aim of present study was to evaluate whether a feedback regulation of pancreatic enzyme secretion exists in cholecystectomized patients. The study was carried out in 12 healthy volunteers and in 6 cholecystectomized patients, 7-14 years (mean 9 years) after the operation. Pancreatic secretion was stimulated by intraduodenal infusion of L phenylalanine (100 mmo 1.1-1). The calculated outputs of pancreatic alpha-amylase and lipase were estimated. The feedback phenomenon was studied using consecutive intraduodenal infusion of trypsin (300 mg/h) and aprotinin (1.5 x 10(6) KIU/30 min). In 6 healthy persons, the infusion of trypsin caused a significant decrease (35-45%) in phenylalaninestimulated alpha-amylase and lipase outputs (p less than 0.05). This effect was completely reversed by intraduodenal aprotinin infusion. In contrast, the increase or the inhibition of tryptic activity in the duodenum was without any effect on pancreatic secretion in cholecystectomized patients. A feedback control of pancreatic secretion could not be demonstrated in patients 6 14 years after cholecystectomy. PMID- 2102985 TI - Effect of long term insulin infusion into rat portal vein on regenerating liver. AB - The effect of long term intraportal infusion of insulin on liver regeneration has been studied in rats 24, 36 and 48 hrs after partial hepatectomy. Our studies showed an enhancement by insulin of some parameters of rat liver regeneration, i.e. a rapid increase of the DNA and RNA levels as well as the TTK activity in the whole liver homogenate and all the subcellular fractions examined. The influence of insulin was marked during the whole time of experiment, but the most significant changes occur during the first 24 hrs after partial hepatectomy. PMID- 2102986 TI - The surgical approach to hyperinsulinism and hypoglycemia in children. AB - Authors present 19 children aged from 2 weeks to 16 y with severe hypoglycemia. In 3 oldest children a single nesidioma was found. In other 16 children mainly infants nesidioblastosis has been recognised, and in those cases the subtotal pancreatectomy was performed. In 4 infants the additional resection of the pancreas was done because after the primary procedure hypoglycemia persisted. All patients survived and were euglycemic. Severe hypoglycemia leads to brain damage and therefore should be treated as an urgent state. PMID- 2102987 TI - An ultrastructural stereologic study of mitochondria in the neonatal adrenal cortex of the rat. AB - The ultrastructural changes observed during the neonatal period of the rat adrenal cortex are described. The zona juxta-medullaris cells presented round mitochondria with vesicular cristae and large endoplasmic reticulum. Variations on the surface of the mitochondrial cristae were determined by morphometric methods. The cortical cells of 1 and 10-days-old rats showed a well developed endoplasmic reticulum. Morphological analysis indicate that the number of mitochondrial cristae increase the third day, followed by a decrease. At the tenth day a second increase was observed. Plasma corticosterone was also measured. The highest levels of this hormone were found in the 1, 2 and 10-days old rats. A decrease was observed in rats of 3 to 8 days of age. This result is coincident with the adrenal changes observed in the developing of mitochondria and endoplasmic reticulum in the neonatal period. The increase in the number of mitochondrial cristae in the three-days old rats can be considered a morphological expression of the neonatal gland in the period influenced by maternal dependence. The most important morphological and metabolic changes observed the second week of life are probably due to the maturation of the hypothalamic pituitary axis that stimulates the neonatal adrenal cortex secretion, which is independent of maternal dependence. PMID- 2102988 TI - Localization of sugar-binding proteins in Trypanosoma cruzi using gold-labeled neoglycoproteins. AB - Neoglycoproteins labeled with colloidal gold particles were used for the ultrastructural localization of sugar-binding sites in epimastigote, amastigote and trypomastigote forms of Trypanosoma cruzi. Binding sites for N-acetyl-D glucosamine and D-galactose were seen on the surface of about 80% and 5 to 10% of the trypomastigote forms, respectively. They were inhibited by addition of the respective monosaccharides to the incubation medium. Binding sites for D-mannose were not observed in trypomastigotes. No labeling of the surface of amastigote and epimastigote forms was observed with the neoglycoproteins which bind to N acetyl-D-glucosamine, D-galactose and D-mannose-binding sites. Labeling of the nucleus and the kinetoplast with the neoglycoprotein which recognizes N-acetyl-D glucosamine binding sites was observed. The results obtained are discussed in relation to the possible role which surface sugar binding sites play in the process of T. cruzi-host cell interaction. PMID- 2102989 TI - Giardia lamblia attachment to biological and inert substrates. AB - Analysis of the attachment basis of Giardia lamblia 1/Portland strain trophozoites to confluent MDCK (Madin Darby Canine Kidney) cell monolayers and type I collagen films, demonstrated, by the use of light and electron microscopy, that the ventral disk as well as the ventrolateral border are the structures involved in the substrate adhesion. Furthermore, we noticed that trophozoite attachment is more effective to collagen than to the apical surface of the epithelium. We described, for the first time, a rounded shape structure evaginated from the naked area that seems to be the ventral disk contact site between the trophozoite and the substrate. This structure has also been observed when the trophozoite is attached to coverslip glass or among trophozoites in close contact. PMID- 2102990 TI - What is caught in neural nets? PMID- 2102991 TI - Ambiguity in 3-D patterns induced by lighting assumptions. AB - A bistable pattern is shown with white and black bars with horizontal and vertical orientations which produce an impression of thin slabs stacked up in depth either toward or away from the observer. It is postulated that the ambiguity is induced by the observer's assumption of the direction of the light source. PMID- 2102992 TI - Wallpaper illusion: cause of disorientation and falls on escalators. AB - The wallpaper illusion, first described over a century ago, can occur when a person with normal binocular vision views a pattern that is periodic in the horizontal meridian of the visual field. Escalator trends present such a pattern. Evidence is presented favoring the view that disorientation experienced by escalator riders is caused by this illusion. Possibly some of the estimated 60,000 escalator falls occurring in the United States each year are linked to it. PMID- 2102993 TI - Effects of direction and magnitude of horizontal disparities on binocular unmasking. AB - Conditions under which binocular unmasking (BU), as an analogue of binaural unmasking, occurs have been explored. Observers were to detect through a stereoscope a Gabor signal in patches of two-dimensional broadband gaussian noise surrounded by a frame of uniform noise. The right-eye gaussian field was displaced relative to the left eye so that it appeared either in front of or behind the frame. Performance when signal disparity was equal to that of the noise--a condition functionally equivalent to monocular processing--was compared to that obtained when signal disparity was zero--a case in which BU should occur. Enhanced signal detectability of up to 12 dB and of nearly constant magnitude was observed in the latter condition when uncrossed disparities of up to 67.60 min visual angle and display durations of 1 s were employed. Signal detectability declined appreciably with increasing disparity (both crossed and uncrossed) when display duration was reduced to 90 ms, thus preventing the occurrence of compensatory vergence eye movements. It is suggested that BU effects may result from a process of linear summation of monocular inputs. PMID- 2102994 TI - Static depth cues do affect the perceived direction of motion. AB - Models of motion perception usually assume that the visual system references spatial displacements to retinal coordinates, and not to three-dimensional coordinates recovered by a parallel process. The present studies investigated whether moving elements viewed in the context of a static random-dot stereogram could lead to the appearance of motion in depth. Observers judged the velocity of a monocular element translating horizontally in the stereo context as 'same as' or 'different to' that of a standard. Based on velocity constancy, if there was apparent motion in depth, the relative velocity judgments would yield a predictable pattern of errors. The first experiment compared two stereo contexts: a sloped surface versus a fronto-parallel plane at zero disparity. The results indicated an overall increase in the perceived velocity of the element moving in the sloped surface context. A similar pattern of results was found when surfaces differing in incline were compared. Experiment 2 explored the case of fronto parallel planes at crossed and uncrossed disparities. Here depth differences did not systematically affect observers' judgments. It was concluded that in some cases motion analysis can be affected by three-dimensional disparity information and not by angular displacement alone. PMID- 2102995 TI - Illusory displacement of equiluminous kinetic edges. AB - A stationary window was cut out of a stationary random-dot pattern. When a field of dots was moved continuously behind the window (a) the window appeared to move in the same direction even though it was stationary, (b) the position of the 'kinetic edges' defining the window was also displaced along the direction of dot motion, and (c) the edges of the window tended to fade on steady fixation even though the dots were still clearly visible. The illusory displacement was enhanced considerably if the kinetic edge was equiluminous and if the 'window' region was seen as 'figure' rather than 'ground'. Since the extraction of kinetic edges probably involves the use of direction-selective cells, the illusion may provide insights into how the visual system uses the output of these cells to localize the kinetic edges. PMID- 2102996 TI - Low-frequency filtering and the processing of local-global stimuli. AB - The role of low-spatial-frequency information in the processing of global stimuli made up of local elements was examined. After selective removal of low spatial frequencies two major changes occurred in the pattern of results. First, response times to global stimuli were significantly slower and the usual speed advantage of global over local processing was lost. Second, when processing local features the usual decrease in response speed when the local and global letters are not the same (consistency effect) was not obtained. These effects could not be explained by changes in error rate, by contrast variation resulting from the process of filtering, or by loss of visual sensitivity due to greater eccentricity of global images. PMID- 2102997 TI - Structural information processing in peripheral vision. AB - Structural visual information processing was investigated in peripheral vision. Perceptual completion, as observed at the blind spot, occurred across a vertical blank stripe in a test pattern, presented in the peripheral visual field. That is, a shape, organized by structural processing, was perceived under critical visual conditions when it was presented in peripheral vision. The results indicate that structural processing, as indicated by perceptual completion, occurs in the peripheral visual information handling process. The results suggest that structural processing of shape information is built into the peripheral visual system and reduces the information load on the higher visual processes under conditions in which visual information is not adequate. PMID- 2102998 TI - Projective invariance and picture perception. AB - Four experiments test the assumption that, in the visual perception of pictures, observers have reliable and direct access to the equivalence of shapes in projective geometry. The assumption is that perception of projective equivalence is the basis of shape constancy ('the projective thesis'). Observers matched or reproduced abstract planar shapes under conditions of rotation in the picture plane, and pictured rotation in depth. Departure from projective equivalence was assessed in each study by measuring the planar analogue of cross ratio. Projective equivalence was not found to be perceived uniformly where Euclidean equivalence was not judged uniformly, either in recognition tasks or in production tasks. When the projective thesis is put to a suitably general test, confidence in the thesis is undermined. PMID- 2102999 TI - Reaction time measures of feature saliency in schematic faces. AB - Two separate paradigms utilizing measurements of reaction time were employed to study facial feature saliency in schematic line drawn faces. In the first paradigm the speed of response to the omission of different facial components was measured, and in the second, the speed of response to feature substitution was measured. In both paradigms the facial features were presented in a random temporal sequence in order to minimise preferential scanning strategies. The two separate paradigms reflected the feature hierarchy most commonly found in the literature, ie the outline and eyes are more salient than the nose and mouth in terms of both speed of processing and error rate. In a third study the feature substitution paradigm was used to investigate the effects of feature saliency on the perception of emotional faces. The results suggest a change in the eyes/mouth hierarchy so that the mouth becomes the most salient feature in the surprised, happy, and sad target faces. This reverse in hierarchy, however, was not evident with the angry target face. These results are discussed in terms of changes in the focus of 'attention' and/or changes in 'processing efficiency'. PMID- 2103000 TI - Visual perception and the guidance of locomotion without vision to previously seen targets. AB - Two experiments were performed to assess the accuracy and precision with which adults perceive absolute egocentric distances to visible targets and coordinate their actions with them when walking without vision. In experiment 1 subjects stood in a large open field and attempted to judge the midpoint of self-to-target distances of between 4 and 24 m. In experiment 2 both highly practiced and unpracticed subjects stood in the same open field, viewed the same targets, and attempted to walk to them without vision or other environmental feedback under three conditions designed to assess the effects on accuracy of time-based memory decay and of walking at an unusually rapid pace. In experiment 1 the visual judgments were quite accurate and showed no systematic constant error. The small variable errors were linearly related to target distance. In experiment 2 the briskly paced walks were accurate, showing no systematic constant error, and the small, variable errors were a linear function of target distance and averaged about 8% of the target distance. Unlike Thomson's (1983) findings, there was not an abrupt increase in variable error at around 9 m, and no significant time-based effects were observed. The results demonstrate the accuracy of people's visual perception of absolute egocentric distances out to 24 m under open field conditions. The accuracy of people's walking without vision to previously seen targets shows that efferent and proprioceptive information about locomotion is closely calibrated to visually perceived distance. Sensitivity to the correlation of optical flow with efferent/proprioceptive information while walking with vision may provide the basis for this calibration when walking without vision. PMID- 2103001 TI - Outlined elements, regular elements and coincidences in illusory-figure patterns. AB - When elements in a pattern which would otherwise produce an illusory figure are modified by outlining or by increasing their regularity (in accordance with a proposed measure of the latter quality), the illusory effect is much reduced. Both results reflect the principle that 'coincidences' in a display play little or no role in the process of segmentation when other circumstances tend to force critical edges to 'belong' to individual elements of the display. PMID- 2103002 TI - Carrier-mediated outward transport of noradrenaline from adrenergic varicosities. AB - Normally, the carrier of the neuronal noradrenaline uptake mechanism (uptake1) is involved nearly exclusively in the inward transport of substrates. However, an outward transport is induced by either of two mechanisms: a. by the decrease (or reversal) of the Na+ concentration gradient across the neuronal membrane or b. by the "facilitated exchange diffusion" due to the inward transport of substrates of this carrier. In rat vasa deferentia (preloaded with 3H-noradrenaline; vesicular uptake, MAO and COMT blocked) all substrates of the carrier induced an outward transport of 3H-noradrenaline, in strict correlation with their Km for uptake1. The inward transport of these substrates increases the availability of the carrier on the inside of the neuronal membrane. However, additional factors contribute to this release: inhibition of re-uptake and co-transport of Na+ and Cl-. When vesicular uptake and MAO are intact, the strict correlation between Km and releasing effect was not seen. This is attributable to the very low axoplasmic concentration of 3H-noradrenaline under these conditions (i.e. to lack of substrate for outward transport). However, if substrates of uptake1 are also substrates of vesicular uptake, they are able to "mobilize" vesicularly stored 3H noradrenaline and, hence, to induce substantial outward transport. These "good" releasers are identical with the "indirectly acting sympathomimetic amines" (i.e. they are tyramine-like). PMID- 2103003 TI - Neuropeptide Y and behaviour: effects of intrastriatal NPY on circling behaviour of rats. AB - Neuropeptide Y (NPY) is a member of the pancreatic polypeptide family and consists of 36 amino acids, sharing sequence homologies with the putative gut hormone peptides YY and PP. NPY dose-dependently stimulates food intake when administered icv into the paraventricular hypothalamic nucleus of rats. Icv NPY has also been reported to decrease locomotor activity, rearing and grooming behaviour. Little behavioural research focusing on other unconditioned behaviours has been conducted. However, intrastriatal injections of NPY have been shown to increase dopamine (DA) turnover there. As unilateral manipulations of central DA result in turning away from the side of higher DA activity, it is of interest to evaluate the effects of intrastriatal NPY on this behaviour. Preliminary results indicate that NPY produces a significant contralateral turning bias when injected directly into the striatum. This raises the intriguing possibility that contralateral turning induced by intrastriatal NPY may be mediated by DA. PMID- 2103004 TI - How do neuropeptides alter cognitive performance? AB - It is pointed out in this article that efficient cognitive performance depends on two independent parameters, one concerned with the intrinsic capacity of the nervous system, the other with motivational processes such as arousal. It is argued that a substance should be regarded as a true cognition enhancer only if it improves the former. There is evidence suggesting that some neuropeptides--for example vasopressin--act on motivational and arousal processes, and a model which offers a plausible mechanism is discussed. The need for techniques and designs which permit us to separate these different effects is highlighted. PMID- 2103005 TI - Proteolysis in neuropeptide processing. AB - The paper reviews the functions of proteolytic enzymes in processing intracellular peptides. The enzymes may "activate" precursors of active peptides, "inactivate" active peptides by their degradation to biologically inactive forms, and "change" the peptides degrading biologically active forms to smaller peptides of different biological activity. The results of own studies on angiotensin II and its fragments are quoted to illustrate how various fragments of the peptide may display various biological activity. PMID- 2103006 TI - Effects of organophosphates on bioelectrical activity of the brain. AB - Effects on electroencephalogram of acute and chronic exposure of two main groups of organophosphates: classic anticholinesterases (OP) and new bicyclic organophosphates (PTBO) are described. The role of muscarinic receptors of the midbrain reticular formation in the mechanism of action of OP and the possible mechanism of action of PTBO as blockers of a chloride ionophore of the GABA receptor complex are presented. The mechanism of convulsive activity of both groups are also discussed. PMID- 2103007 TI - Assessment and treatment of Spanish-speaking sex offenders: special considerations. AB - While there is an expanding body of literature pertaining to the special considerations related to the treatment of Hispanic patients whose primary language is Spanish, there is virtually no information reported to aid in the assessment and treatment of Hispanic and primarily Spanish-speaking sex offenders. Beyond the obvious problems posed by differences in language, there are a host of transcultural factors that may impact on the evaluation and engagement of this patient population when they are also largely psychologically unsophisticated and from a low socioeconomic level. The experiences in modifying and implementing a special program to accommodate the needs of this patient group is presented. Reticence to discuss sexuality in a group setting, the relationship between therapists and patients as effected by rules of social etiquette, and the reluctance to criticize other members in the group were prominent features attributed to religious and cultural factors. The authors consider it a necessity to be sensitive to these subtle nuances in order to provide adequate treatment. PMID- 2103008 TI - Mentally ill chemical abusers discharged from VA inpatient treatment: 1976-1988. AB - Discharge abstracts were analyzed for all patients discharged from Department of Veterans Affairs (VA) medical centers with a primary non-substance abuse psychiatric diagnosis over a twelve year period (1976 to 1988). Patients were identified as Mentally Ill Chemical Abusers (MICAs) if they had a primary mental illness diagnosis and either a secondary substance abuse diagnosis or an admission for substance abuse treatment during the same fiscal year. The percentage of MICAs doubled, from 22.6% to 43.6%, during these twelve years. In 1988, MICAs were younger and more likely to be minorities than other VA psychiatric patients, and they spent only half as many days in the hospital per year. PMID- 2103009 TI - Psychiatric hospitalization and community-based program attendance. AB - The psychiatric rehabilitation model of community-based treatment programs for chronic psychiatric patients advocates the teaching of community living skills. Learning these skills requires program attendance, and there is some evidence that consistent attenders are less likely to be hospitalized. This study describes a psychiatric rehabilitation program that resulted in a decrease in number of subsequent psychiatric hospitalizations. However, this decrease was unrelated to program attendance; the number of hospitalizations in the year prior to enrollment was by far the best predictor of hospitalization. Changes in perception of the patient's support network by persons making hospitalization decisions was offered as one possible explanation for the effectiveness of some community-based programs. PMID- 2103010 TI - The therapeutic use of humor for psychiatric disturbances of adolescents and adults. AB - The use of humor in psychiatric care and treatment is examined within a life-span development context, comparing its utility in late adolescence with that in early adulthood. The literature of the past two decades, based on careful experimental research as well as on more subjective clinical experience, tend to support the following conclusions: A well-developed sense of humor provides a beneficial ingredient to the patient's coping or adjustive ability. The salutary physiological effects of laughter are the same for adolescents and adults. In terms of psychosocial factors, individual rather than developmental stage differences in the patient's personality, psychopathology and humor preference will alter the effectiveness of humor application. According to a cognitive behavioral analysis, the mechanism by which positive emotions (including laughter) operate to reduce or eliminate the undesirable negative emotions resides in the interplay of the physiological and psychological processes involved in the stress reaction and its management. Finally, to be optimally effective the psychiatrist should undertake formal training in the use of humor techniques comparable to the traditional training in the usual assessment and therapeutic procedures. PMID- 2103011 TI - Sexually deviant behavior and schizotypy: a theoretical perspective with supportive data. AB - Sexual offenses against adults and children continue to increase annually. Although theory and research have helped explain the personality functioning and motivation of sexual offenders, most treatment approaches have been found to have high recidivism rates and have failed to address the heterogeneity of sex offender populations. In the present paper, we utilize the growing literature on schizotypic personality organization to describe a subgroup of sex offenders. Data from the sex offender personality literature which indicates signs of thought disturbances among some sex offenders are reviewed in the context schizotypy. We conclude that treatment programs which address the heterogeneity of sex offenders and employ interventions to treat cognitive disturbances will likely result in greater efficacy. PMID- 2103012 TI - Nonpsychiatric consultations within a general hospital psychiatric unit: characteristics and concordance. AB - Nonpsychiatric consultations to a general hospital psychiatric unit were investigated for concordance with diagnostic testing advice, drug recommendations, and representation of the medical diagnoses in the discharge summary. Those patients who received consultations were older and had less social support but did not have more severe medical illnesses. The level of concordance with medical consultants' recommendations was far greater than previous reports of psychiatric consultants' advice to nonpsychiatric colleagues. PMID- 2103013 TI - Psychiatric disorders of abused women at a shelter. AB - Thirty physically abused women were randomly selected from the population of a local women's shelter and evaluated by psychiatric interview and psychiatric rating scales. High prevalences of major depression disorder (37%) and PTSD (47%) were determined. Furthermore, these disorders were found to be positively associated. These results suggest the need for immediate availability of psychiatric services at such shelters along with further study of their populations and possible intervention strategies. PMID- 2103014 TI - [Remote results of prosthetic treatment of patients with nickel hypersensitivity]. AB - Economic reasons are the cause that ever more frequently prosthetic replacements are made from alloys other than gold. The most widely used are: alloys based on nickel and chromium, and stainless steel. In some alloys the content of nickel may be over 80%. The studies carried out in early 1980s showed that these materials had a higher hardness, mechanical strength and elasticity module than gold alloys. Nickel is one of the main components of these alloys, and its compounds may exert a harmful toxic, and even more frequently, allergic effect on the human organism. In the light of a survey of the literature and own clinical, experimental and epidemiological investigations it was tried to trace the effect of dental replacements made of nickel-containing alloys on the mucous membranes and skin of subjects with confirmed hypersensitivity to nickel. The studied material comprised a group of patients selected at random from those attending the Allergology Outpatient Clinic at the Department of Dermatology, Medical Academy in Warsaw, who had verified hypersensitivity to nickel and had indications to preparation of crowns and bridges for wearing. In each case before and after prosthetic treatment and before any control stomatological examination patch tests were done for demonstrating nickel hypersensitivity. In all patients permanent prostheses were done from an allow containing up to 70% of nickel with baked porcelain. In most cases fragments of oral mucosa were taken for histological examination. The patients were examined twice yearly. The longest follow-up is presently over 8 years. In no case exacerbation of hypersensitivity reactions was noted. PMID- 2103015 TI - [Assessment of the condition of the stomatognathic system in the students of the High Navy School in Szczecin. 1. Study before one-year cruise]. AB - The authors carried out clinical examination of 227 students of the first year of the High Navy School in Szczecin. The aim was to assess the condition of the stomatognathic system at the beginning of the study and to compare the local conditions of the oral cavity after one year cruise in a ship. On the basis of the study it was found that most students had normal occlusion, bite with canine covering, and mixed. The mean DMF score was 10.84. Functional changes in the temporomandibular joints were disclosed in 9.1% and parafunctions in 40.08%. Teeth attrition was found in 36% of the students. PMID- 2103017 TI - [Disinfection and sterilization in clinics and laboratories of dental prosthetics]. PMID- 2103016 TI - [Trial of replacement of ABC cement with the preparation Evicrol in fusing metal alloys used in prosthetic to the enamel]. AB - The fusion strength was compared of the main metal alloys (Wiron 88, Wironit, Spal, Super Fluid) to the enamel by means of the ABC cement (Vivadent) and the preparation Evicrol (Spofa Dental). The obtained samples of metal alloys were subjected to abrasive blasting processing, defatted, and covered with the preparation "metal primer" from the ABC set, and fused to the pickled enamel with ABC cement and Evicrol preparation. The strength of the fusion was tested with the Instrom testing device. The fusion strength was greater in the case of Evicrol. PMID- 2103018 TI - [Method of preparing an otic insert in a case of narrowing of the external auditory meatus]. AB - The authors present three cases of patients hard of hearing in whom narrowing of the external auditory meatus was found. The application of individually prepared insert with diameter greater than that of the meatus improved the hearing acuity without producing any side effects. PMID- 2103019 TI - [Gdansk combined crown with occlusal rest. 1. Clinical and laboratory preparation of combined crown with occlusal rest on the basis of cast crown]. AB - The combined crown used since many years in the Prosthetic Laboratory, Institute of Stomatology, Medical Academy in Gdansk contains an occlusal rest basis of a cast crown (the metal part is of a gold alloy or chromium-nickel steel, with veneer of acrylateor Colorstat) provides, owing to a special preparation of the abutment tooth and laboratory procedure, full stabilization of the crown, protection of parodontium and good maintenance of the veneer which plays a cosmetic role in this type of crown. The combined crowns with occlusal rest are particularly suitable for supporting bridgeworks. They may be applied onto devitalized or live teeth since they require less extensive grinding of teeth. PMID- 2103020 TI - [Pathogenetic role of nickel in human organism]. AB - The ever increasing presence of nickel in nature and human food has made it the subject of growing interest of research workers in various medical discipline. Its allergizing, toxic, mutagenic and carcinogenic causes justified concern of those who use it in orthopaedics and stomatology. The frequency of contact allergy to nickel has called attention to its use in production of many daily utility objects. The probability of allergy is not limited only to persons with occupational exposure to this element but it becomes ever more widespread in the whole population. The role of nickel in contact allergy is well known, and a particular feature of this allergy is the character of allergens which are simple haptens with respect to their antigenic. More detailed data on the mechanism of contact allergy have been provided by the discovery of Langerhans cells which have the ability of antigen presentation. Considering the role of nickel in pathological conditions we must not forget its great physiological importance as a microelement necessary for life. PMID- 2103021 TI - [Views on the use of nickel alloys in oral cavity]. AB - The biological tolerance of permanent prosthetic replacements made of nickel containing alloys has been the subject of discussions for years. In the past, allergic contact reactions in the mucosa were rarely observed, and as a rule they were always connected with present or imminent skin allergization. The studies of some authors on the frequency of nickel hypersensitivity in persons wearing prosthetic replacements containing nickel showed usually no differences in comparison with control groups having no such replacements. However, in the literature many reports were published also disqualifying these alloys in view of the allergizing effect of nickel released from them in the mouth. A survey of the literature gives thus no clear-cut conclusions concerning the use of alloys based on nickel in stomatological prosthetics. PMID- 2103022 TI - [Analysis of disturbances in the intra-articular conditions in temporomandibular joints in patients with suboccipital pains in relation to the type of dental loss]. AB - The studies material comprised 49 patients with suboccipital headaches and functional disturbances of the stomatognathic system. In the patients radiograms were taken of the temporomandibular joints by Schiller's method, clicks in these joints were analysed, and the type of teeth loss was studies. It was found that the extent and type of teeth loss had a significant effect on the occurrence of disturbances in the intra-articular conditions in these joints in the position of the mandibular heads and on the presence of clicks in the joints. PMID- 2103023 TI - [Chronic pains of suboccipital and upper cervical area and functional disturbances of the stomatognathic system]. AB - The purpose of the work was to investigate the relationships between functional disturbances of the stomatognathic system and the occurrence of chronic pains in the suboccipital and upper cervical areas. In 37 patients clinical observations were done and in 25 cases radiograms of this part of the cervical spine were taken. A correlation was noted between pains in the cervical spine and mandibular parafunctions, disturbed mandibular movements, pains in the muscles on mandibular movements. PMID- 2103024 TI - [Effect of clinical and laboratory management in preparation of combined crowns faced with porcelain on the state of periodontal soft tissues]. AB - The effect of clinical management and laboratory procedures during preparation of porcelain-faced combined crowns is discussed. Attention is called to proper grinding of dental surfaces, with particular reference to the area near the gingiva. The result of the treatment with porcelain-faced crowns depended not only on the clinical management but also on a proper shape of the metal part of the crown and proper laying and baking of porcelain. This procedure should be done strictly according to the instruction of the producer. PMID- 2103025 TI - [The Cracow modification of the Calotte method of teeth placement in clinical evaluation]. AB - The purpose of the paper was checking of theoretical principles and assessment of the clinical usefulness of the calotte method of teeth placement in Cracow modification. In 110 patients this study was carried out according to the following schema: prosthetic treatment using complete prostheses with teeth placed by the modified method or by the Gysi-Fischer method, for comparison, and periodically repeated clinical examinations considering such elements as: articulation and occlusion, fixation and statics of prostheses, masticatory function and speech, and aesthetic result and adaptation process. In all these parameters good results were obtained by the modified method. It is concluded that the modification is particularly useful in therapeutically difficult cases, with unfavourable anatomic-physiological conditions of the denture bearing area. PMID- 2103026 TI - [Teeth placement in complete denture by the Calotte method in Cracow modification]. AB - Theoretical principles and the modification of the calotte method of teeth placement in complete prosthesis are presented. The method combines the elements of the articulation and static theories, but is easy for teaching and introduction, is not requiring a change of the clinical management (in relation to the generally accepted principles) or use of special devices of articulators which are presently unavailable. Checking of correct teeth placement is also easy. The method is thus simplified and thus possible for application in laboratories with average technical equipment. PMID- 2103027 TI - [Gdansk combined crown with occlusal rest. 2. Clinical assessment of the combined crown with occlusal rest on the base of cast crown]. AB - Thirty patients receiving 53 combined crowns with occlusal rest are described. The results are presented in tables. Poor marginal contact was found in about 20% and only 25% of the crowns penetrated into the gingival pouch at a distance over 0.6 mm. PMID- 2103028 TI - [Studies on the relationship between functional disturbances of stomatognathic system and chronic suboccipital headaches]. AB - The studied group comprised 139 patients with functional disturbances of the stomatognathic system. The effect was analysed of certain local factors causing functional disturbances of the stomatognathic system on the occurrence of chronic suboccipital headaches, and causative stomatological-prosthetic treatment was given. The obtained results confirmed the relationship between certain symptoms of functional stomatognathic system disturbances and chronic suboccipital headaches in these patients. PMID- 2103029 TI - [A trial of determination of the range of physiological teeth mobility with the Periotest device]. AB - The purpose of the study was determination of the range of the physiological mobility of teeth measured with the Periotest Siemens. The apparatus makes possible a dynamic measurement of the reaction of the suspending system of the teeth to blows of known strength. The measurements with Periotest characterize not only the clinical mobility of a tooth but also the elasticity of the periodontium. The measurements were done in 47 objects, 35 women and 12 men. In a group of 10 women the measurements were repeated many times, for checking the objectivity of the method. The results demonstrated that various groups of teeth differed with respect to mobility; the lowest values were obtained for lower canines and premolars, the highest ones for medial incisors in the mandible. The values determined with Periotest were usually smaller for the mandibular teeth than for the maxillary teeth, and smaller in men than in women. Determination of the physiological range of teeth mobility forms a reference point for the evaluation of periodontal changes. PMID- 2103030 TI - [Effect of impression contamination on the accuracy of plaster model surface]. AB - Macroscopic and microscopic examination of plaster models obtained from impressions with alginate mass Kromopan Super and silicone mass Dentaflex Pasta confirmed that leaving of saliva and blood on the surface of impressions causes uneven surface of plaster models. For ensuring sufficiently even surface of the model the impression should be cleaned immediately after its obtaining with water and a brush, or later on by immersion in 2% Na2SO4 solution. PMID- 2103031 TI - [Branemark method for preparation of titanium implants integrating with bone. Literature review]. AB - On the basis of a literature survey the Branemark method of preparing implants integrating with bone is presented considering preoperative management, two-step surgical intervention and prosthetic treatment. The results obtained as yet are presented. PMID- 2103032 TI - [Natural cytotoxic activity in patients with oral candidosis]. AB - The natural cytotoxic activity of lymphocytes isolated from patients with oral candidosis during prosthetic stomatopathy was studied. The natural cytotoxic activity test was carried out in a group of 10 patients before treatment and immediately after effective antimycotic treatment. The material for the tests was venous blood of the patients sampled in volumes of 10-15 ml. The results of the test before and after the treatment were within normal range. PMID- 2103033 TI - [Evaluation of pyralgin usefulness in premedication of patients before stomatological treatment]. AB - Pyralgin (metamizole sodium) usefulness was tested in premedication of 90 patients subjected to processing of hard tooth tissues by grinding or drilling. The results of the study demonstrated that about 2/3 of the patients failed to observe any difference in the painfulness of the procedure with and without premedication with Pyralgin. In 1/3 of the patients Pyralgin reduced pain, improved wellbeing and raised the emotional status during the procedure. This effect might be regarded as a placebo result. PMID- 2103034 TI - [Minimalization of the proper parts of retention arms]. AB - Clasps situated on anterior teeth decrease the aesthetic value of the dental arches and the patients want to have the size of the clasps reduced. The study was carried out for finding out what was the least acceptable size of the retention arms of the clasp. A technique was evolved for designing the minimalized retention arms, and it was established that the proper part of the retention arm must exceed the interspace limit by 1 mm. Further shortening of the clasp was not possible. Minimalization of the arms of the clasp decreased the adverse effects of removable prostheses on oral hygiene. PMID- 2103035 TI - [Regeneration of the electromotor force of electric piles in the mouth]. AB - The regeneration of the electromotor force E of the electric piles formed by two amalgam fillings was measured as a function of time t after the moment of interruption of the short contact of their poles. The measurements were carried out in 30 patients at a mean age of 27.0 +/- 08 years. Automatic recording of the equation E = f (t) demonstrated that in the first phase of from several to about a score of seconds the E value rose rapidly, while in the second phase lasting from several scores to over a thousand seconds the E value approached asymptotically its initial value Eo. PMID- 2103036 TI - [Effect of electrochemical etching of alloy surface (Wiron 88 and Wironit) on the strength of alloy binding to enamel by the Microjoin cement]. AB - One of the methods of "adhesive" preparation of the surface of the retention elements of AET bars and brides before their binding to enamel is electrochemical etching. The purpose of the method was creation on alloy surface of appropriate microretention for the fixing resin. The aim of the study was determination of the optimal conditions for etching of alloys (Wiron 88 and Wironit) as binding elements of AET constructions, and for checking the binding force of the Microjoin resin cement. The following etching conditions were accepted as optimal: for the Wiron 88 alloy (10 min, 2,7 V, 200 mA/cm2), for the Wironit alloy (12 min, 2,7V, 270 mA/cm2). The binding force of the alloys etched under optimal conditions to the enamel achieved with the Microjoin (Sci-Pharm-Madental) resin cement was measured also, using the Instron testing device. The movement velocity was 2 mm/min. The following strength of binding of etched alloys to enamel was measured: 195.7 kG/cm2 for the Wiron 88 alloy, and 128.6 kG/cm2 for the Wironit alloy. PMID- 2103037 TI - [Electrochemical etching of alloys as a method for extension of the surfaces of the fixing elements of the AET constructions]. AB - Electrochemical etching of metal alloys is one of the method for obtaining of micromechanical retention on the surface of the fixing elements of AET constructions. On the basis of literature survey and own experiences the author describes the nature of the electrolytic etching of metal alloys for obtaining of retention surface. The effect is described also of etching on the binding force of various metal alloys and resin cements. PMID- 2103038 TI - [Remarks on the article of J. Bielski: height of cusps of artificial teeth and their effect on prosthesis statics and mastication effectiveness]. AB - The author argues with the article of J. Bielski on the usefulness of using artificial teeth with flat masticating surfaces for complete dentures. Quoting the authors studying gnathophysiology and own studies as well as clinical observations he states that such prostheses may be a cause of stomatognathic system dysfunction. PMID- 2103039 TI - [Statics of complete prostheses. 1]. AB - The author discusses the principles of arrangement of artificial teeth in complete prostheses from the standpoint of statics. In the consideration of the action of forces released in the mastication the values of these forces, the application points, the directions of action and vector sense as well as the developing torques are taken into account. PMID- 2103040 TI - [Statics of complete prostheses. 2]. AB - The statics of prostheses in complete absence of teeth is discussed with analysis of the effect of the position of the masticating surfaces of artificial teeth on the values of forces disturbing the balance of the prosthesis during mastication. Considering the friction forces active during mastication, the worse fixation of lower prostheses, and the lateral position of the mandible in relation to the maxilla the author describes as optimal such a spatial arrangement of artificial teeth that in centric occlusion the interalveolar line passes through the centre of their masticating surfaces which are perpendicular to it. PMID- 2103041 TI - [Vertical pathological attrition--causes, consequences and treatment methods]. AB - The mechanism of development of vertical pathological attrition leading to destruction of the palatine and vestibular surfaces of the anterior teeth is described. Vertical pathological attrition is most frequent in acquired occlusal defects after loss of abutement zones, and in certain congenital malocclusions (supraocclusion). This condition may lead to damage to the whole stomatognathic system. Depending on the degree of progression of the pathological changes of this system prosthetic treatment in cases of vertical pathological attrition may be done in one or two steps. For illustration of the methods of treatment of this attrition three cases are presented. PMID- 2103042 TI - [Requirements for permanent replacements in certain population groups]. AB - The analysis is presented of the results of epidemiological studies of 180 subjects of either sex aged 35-44 years from the standpoint of their needs for crowns and bridges. The proportion of subjects in need of prosthetic crowns was 30.55%, while 18.33% required bridges. The material was subjected to statistical analysis. PMID- 2103043 TI - [Fixation of complete lower prostheses with intra-alveolar implants (case report)]. AB - The author describes a female patient in whom complete lower prosthesis had to be made for the first time. For improving the stabilization of the prosthesis had to be made for the first time. For improving the stabilization of the prosthesis and facilitate the adaptation it was planned to carry out intra-alveolar implants by Wierzynski's method inserted into freshly emptied alveoli. The immediate prosthesis was a specially adapted prosthesis which had been worn previously by the patient. After healing of the post-extraction wound and epithelialization of alveoli final prosthetic replacement was prepared, i.e. upper partial prosthesis and lower complete prosthesis with intra-alveolar implant. PMID- 2103044 TI - [Experimental studies of casting contraction of crowns and bridges made of various alloys based on nickel (NI-CR)]. AB - The results are presented of experimental studies of casting contraction of metal crowns and bridges with an attempt at outlining of practical suggestions concerning the choice of materials and work technology with alloys based on nickel. Casting contraction was determined for the following alloys: Gisadent MCA, Gisadent NCS1, Mikrostom-1 and Wiron-88. The need for further studies on alloys based on nickel which may be used for preparation of permanent replacements as substitutes of precious metals is caused in Poland and all over the world by economic factors. PMID- 2103045 TI - [Studies on the response of epithelial cells of the hard palate to prolonged pressure exerted by prosthesis]. AB - Microscopic examination was done of biopsy material of hard palate mucosa in healthy subjects with normal teeth and in edentulous patients with a long history of complete upper prostheses. The examination in transmission electron microscope included cells of the multilayer flat-cell epithelium of the mucosa covering the hard palate. Isolated cilia were found in the cells of the germinative layer and in the lamina propria of the mucosa where they penetrated from the epithelium across the basement membrane. The cilia were present in a significantly higher number of cells in hard palate epithelium subjected to long-term pressure exerted by the prosthesis. On the basis of observations of the structure of cilia and its environment one may assume that this apparatus may serve as an epithelial receptor of local changes produced by long-term and changing pressure of the mucosa through the mediation of masticatory forces transmitted onto the mucosa by the plate of the prosthesis. PMID- 2103046 TI - [Eye signs in patients with functional disturbances of the stomatognathic system]. AB - The authors carried out an analysis of the frequency of eye signs in 429 patients with functional disturbances of the stomatognathic system and found that these disturbances were present in 29.8% of these patients, and the intensity of eye signs depended on the clinical picture of dysfunction. Return of normal function of the stomatognathic system gave complete regression of eye signs in 66.7% out of 36 patients, in 30.5% of cases improvement developed, and in 2.8% local stomatological treatment was unsuccessful. PMID- 2103047 TI - [Prosthetic treatment and needs for this treatment in adults aged 35-44 years in the province of Bialystok]. AB - In randomly selected 180 subjects of either sex aged 35-44 years from a city, a town and a village in the Province of Bialystok (30 subjects in each group) the state of prosthetic management and the needs for prosthetic treatment were analysed. Removable prostheses were worn by 23.3% of the subjects. Over one fourth of the used partial removable prostheses required exchange. In this group of 180 subjects the need for prosthetic management included 168 removable prostheses (including 3 complete ones), 63 bridges and 277 crowns. These data indicate an urgent need for increasing the range of prosthetic treatment for the population of this province. PMID- 2103048 TI - [Effect of mechanical processing on the electrolytic properties of chromium nickel steel]. AB - The purpose of the study was investigation of the electrochemical properties of chromium-nickel alloy which are changed during mechanical processing associated with the preparation of pressed crowns. The laboratory procedures (polishing excluded) exert a harmful effect on the electrolytic potential of the alloy. The procedures are only intermediate phases and are without any significant role, since the end-result is, after annealing and polishing, as expected. However, mechanical processing in dentist's office is quite different. Of interest are the poor results obtained in such mechanical procedures as overbending and becking. These procedures should not be done in dentist's offices also for other reasons. PMID- 2103049 TI - [Classes in prosthetics for stomatology students in the University Stomatology Faculty in Munster (FRG)]. PMID- 2103050 TI - [Spreading of the tick Amblyomma variegatum in the West Indies: how can this serious menace be explained and what should be done?]. AB - The author presents a brief history of the introduction and extension of the African tick Amblyomma variegatum in the Caribbean. The tick is particularly dangerous for the livestock industry because of its role as a vector of heartwater and its association with severe dermatophilosis. It is already distributed in the Lesser Antilles from Puerto Rico to Barbados and St. Vincent. The chronology of its sudden unexplained expansion since the 1960s corresponds well with the multiplication of the cattle egret (Bubulcus ibis) in the region, while the tick had hardly extended its distribution during more than 130 years, before this African bird arrived in the western hemisphere. These birds are often infested with larvae of the tick and carry out important movements between islands. The imminent invasion of the American continent appears unavoidable, with incalculable disastrous consequences for the livestock industry, unless the tick is rapidly eradicated from all infested islands. While presenting practical, human and social problems, eradication from the islands is technically feasible and its cost/benefit ratio is very positive. PMID- 2103051 TI - An outbreak of gizzard erosion and ulceration in chicks in Zambia. AB - An outbreak of gizzard erosion and ulceration in broilers in Zambia is described. Approximately 100,000 chickens in the age group of 2-9 weeks were affected. Mortality ranged from 5 to 30%. In a majority of cases, crops, oesophaguses and gizzards were engorged with dark brown to black watery material. Lesions were mainly in the gizzard comprising erosions and ulcers. High levels of fish meal in the ration is indicated as a causative factor. PMID- 2103052 TI - [Serological survey in a Sahelian country, the Niger. Sampling problems and results of the serosurveillance of rinderpest]. AB - A survey on Rinderpest serology was conducted in Niger with a sample of 2815 sera. The authors present the sampling method and resulting bias. The analysis of the sera is discussed according to the following factors: sex, age, vaccination status and geographic origin of the sera. PMID- 2103053 TI - Mycoplasmas from donkeys and horses in the Sudan. AB - Seventeen isolates (4.27%) were recovered from 398 samples. Twelve isolates (4%) were obtained from 300 donkey nasal swabs, three (4.3%) and two (6.89%) isolates were recovered from 69 horse nasal swabs and 29 mare uterine washings, respectively. Nine isolates were lost during storage at -20 degrees C and the remaining eight were identified as mycoplasmas and their biological, biochemical and serological reactions were investigated. The isolates could be divided into two groups on the basis of glucose fermentation and arginine hydrolysis. The first group neither fermented glucose nor hydrolysed arginine. Organisms in the second group hydrolysed arginine only. PMID- 2103054 TI - [Sensitivity of double microcentrifugation for the research of trypanosomes]. AB - The double microcentrifugation technique, described by KRATZER and ONDIEK (1989) for the parasitological diagnosis of trypanosomes, has been tested both in the laboratory and in the field. The limits of detection obtained here were not as low as those described in the original experiment, but the sensitivity of this technique for the detection of Trypanosoma brucei, T. congolense and T. vivax was better than the phase contrast buffy coat method. This technique, which is easy to apply in the field, is highly recommended, especially for epidemiological surveys. A protocol and a list of equipment are included. PMID- 2103055 TI - Effects of the timing of antigen stimulation on parasitaemia profile and subsequent immunodepression in an experimentally induced Trypanosoma brucei infection. AB - The influence of administering sheep red cells (SRC) as antigens, either after or before a trypanosome challenge, on parasitaemia profile and antibody response was assessed in albino Wistar rats. High levels of parasitaemia associated with significantly depressed antibody response and packed cell volume (PCV) values were observed when trypanosome challenge preceded antigen stimulation. In contrast, a clear delay in the onset and development of parasitaemia occurred when antigen priming preceded trypanosome challenge. At the beginning, PCV values and antibody response to the antigen were in the range of levels found in control rats. However, as infection progressed, parasitaemia rose and significant immunological hyporesponsiveness developed which at least reached levels found in rats that had received trypanosome challenge prior to antigen stimulation. These findings should be taken into consideration when evaluating serological tests used for assessing responses to specific vaccinations, or for the diagnosis of infections based on rising antibody titres in the host. PMID- 2103056 TI - [Chemoprevention of bovine trypanosomiasis in N'Dama cattle imported from the Senegambia and Zaire to Gabon]. AB - A programme of chemoprophylaxis against trypanosomiasis has been work out for the protection of newly imported N'Dama cattle from the Gambia, the Senegal and Zaire into Gabon. The transfer induced a deficiency in their trypanotolerance. Isometamidium chloride and diminazen aceturate were used. PMID- 2103057 TI - Note on an epidemic of coccidiosis in domestic rabbits in the Plateau and Bauchi states, Nigeria. AB - During an epidemic of intestinal coccidiosis, 1128 young domestic rabbits died out of 2385 animals examined. Nine species of Coccidia were identified with a minimum of five different species per rabbit. Clinical and necropsy findings as well as treatment and control measures are described, epidemiology and pathogeny are discussed. PMID- 2103058 TI - Note on Onchocerca armillata in the Sudanese camel (C. dromedarius). A histological and anatomo-pathological approach. AB - Aortic onchocercosis due to O. armillata was diagnosed in 45 (41%) out of 109 Sudanese camels. Although the thoracic aorta was regularly affected, involvement of other vessels such as the abdominal aorta, brachiocephalic, pulmonary and costocervical arteries was not excluded. Gross examination of the affected blood vessels revealed tortuous tunnels of parasitic tracks readily visible in the intimal surface of the vessels. Nodular lesions were more common on the adventitia. Microscopically, the lesions showed irregulary elevated intimal surfaces. The underlying tunica media contained a varying number of encapsulated and partially mineralized parasitic fragments. The inflammatory response varied in intensity and location and consisted of eosinophils, lymphocytes, macrophages and occasional giant cells. PMID- 2103059 TI - [Peripheral arteriosclerosis obliterans]. PMID- 2103060 TI - [Comparative study of circulatory response to tracheal intubation with atracurium and succinylcholine]. AB - Changes in some circulatory parameters after orotracheal intubation (OTI) were investigated in 40 patients anesthetized with thiopental 5.0 mg.kg-1 and fentanyl 100 micrograms, receiving either atracurium 0.5 mg.kg-1 (n = 20) or succinylcholine 1.0 mg.kg-1 (n = 20) to facilitate intubation. In the succinylcholine group (SC), mean values of SAP, DAP, MAP, and HR rose significantly in relation to control at 30 sec and 2 min after OTI. In the atracurium group (A), mean values of SAP, DAP, and MAP rose significantly at 30 sec after OTI, however, contrary to the SC group, mean values of HR did not rise significantly after OTI. Mean values of the double product HR x SAP rose significantly at 30 sec, 2 min, and 5 min after OTI in the SC group, but only at 30 sec and 2 min after OTI in the A group. The magnitude of elevation of those circulatory parameters studied was always greater in the SC group than in the A group. The authors conclude that atracurium does not modify the nature of circulatory changes after OTI but is associated to such changes in a lesser degree when compared to succinylcholine in a standard induction technique with thiopental/fentanyl. PMID- 2103061 TI - [Partial vertical laryngectomies: reconstruction with a platysma myocutaneous flap]. AB - Partial vertical laryngectomies have been performed successfully for nearly one century. Hemilaryngectomies may present more evidence of difficulties and complications and both can be controlled with reconstructive methods. Thus, the authors present 6 patients with T1 and T2 glottic tumors submitted to hemilaryngectomy (5 cases) and to frontolateral laryngectomy (1 case) reconstructed with platysma myocutaneous flap. The oncologic and functional results were analyzed for follow-up from 2 to 5 years. Observation was made of time for decanulization, start of swallowing, presence of oro-tracheal. aspiration, vocal quality (roughness, breathiness, and inteligillity), physical activity, and complications. The authors conclude that such a method does not affect oncologic results and represents an adequate support to the organ, facilitating amplified resections. PMID- 2103062 TI - [Refractory epilepsies]. AB - STUDY OBJECTIVE: To describe the role of multidisciplinary evaluation and general aspects of intractable epilepsies such as age at the onset, etiologic factors, CT scan findings, electroencephalographic abnormalities, types of epileptic seizures, adherence, and crisis-triggering factors. TYPE OF STUDY: Retrospective. SITE: Department of Epilepsy Research and Treatment (SITE)--Sao Paulo, Brazil. PATIENTS: Analysis encompassed 80 epileptic patients registered with the SITE, who had one or more crises per week, with a minimum follow-up of one year, older than 13 and seen between August and October 1989. INVESTIGATIONS: psychologic, social, nursing, and neurologic evaluations. Treatment performed with antiepileptic drugs. MEASUREMENTS AND RESULTS: Mean age at onset of epilepsy = 12.6 years; 70% of patients have symptomatic partial epilepsy; 66.2% had epilepsy onset after 5 years of age; 80% have had epilepsy for more than 10 years; etiology was not determined in 47.5% of the cases and, in 22.5%, it was due to neurocysticercosis; 88.7% of the patients were having anti-epileptic polytherapy; 50% of the patients did not adhere to the treatment; 56.25% reported emotional originating factors; 60% were socially non-adjusted; 30% had abnormal EEG in the right temporal lobe; 26.2% in the left temporal lobe; 21.2% had normal EEG plotting, and the remainder had their EEG with focal abnormalities in other locations. CONCLUSIONS: The authors accept the fact that a patient who does not lead a balanced social, affective, and emotional life should be classified as a probable case of intractable epilepsy. The authors observed that a large portion of the patients could be seen as pseudodifficult treatment cases, since 50% were non-adherent to treatment, and 56.25% reported the presence of emotional originating factors. As most of these patients have social and psychological maladjustments, perhaps due to their high incidence of epileptic crises, they may be cases of intractable epilepsies. PMID- 2103063 TI - [Approach to urinary tract disorders in postmenopausal women]. AB - Urinary disorders in the postmenopausal women are important due to their high incidence and to the negative influence on the quality of life of these women. The authors make a brief review of the pathophysiology of these disorders, emphasizing the significant effects of an estrogen fall on the urinary tract during this period of life. They present a modern approach to the current diagnostic and therapeutic aspects of urinary incontinence, urinary tract infections, and urethral syndrome. They also point out the importance of systemic and/or local estrogen therapy in these different aspects, observing the benefits and risks involved in these therapeutic procedures. They comment on the treatment with antibiotics, with adrenergic and/or anticholinergic drugs, surgical treatment, and the techniques of vesical reeducation in the case of detrusor instability. They recommend that physicians should inform and offer their patients the resources above which lead to the cure and/or improvement of the urinary symptoms of those women, given them an expectation of a longer and better life. PMID- 2103064 TI - [Nonfunctioning parathyroid cyst simulating thyroid nodule]. AB - A parathyroid cyst is a rare disease. A 48 year old man with a nonfunctioning parathyroid cyst is described. The cyst was initially misdiagnosed and taken for a thyroid cyst based on physical examination, thyroid scan, sonography and needle biopsy. Cervical exploration was performed due to the recurrence of the lesion. The cyst was resected and histology showed it to be a parathyroid cyst. Pre and post operative clinical aspects are discussed. PMID- 2103065 TI - Assessment and prediction of asthma and its severity in the pediatric community. AB - Seventy four asthmatic children aged 7 to 11 years were examined along with controls matched by age and sex. Clinical and laboratory investigations preceded a 28-day follow-up where data about morning and evening peak expiratory flow rate (PEF), symptoms and treatment were recorded. The coefficient of variation of PEF was found to be an objective measurement of asthma severity that has statistically significant correlation with both symptoms (rs = .36) and treatment (rs = .60). Moreover, it separates mild and severe asthmatics, as confirmed by statistically significant differences (p = .008 or less) in symptoms, treatment, skin allergy and airways response to exercise. Skin allergy and airways responsiveness to exercise were found to be predictors of both disease and severity. By means of logistic regression analysis it was possible to establish the probabilities for both asthma and severe asthma when children presenting and not presenting these characteristics are compared. One single positive skin test represent a probability of 88% for the development of asthma and a probability of 70% for severe disease. A PEF reduction of 10% after an exercise test implies a probability of 73% for disease and a probability of 64% for severe disease. Increases in these variables imply geometrically increased risks and their presence together have a multiplicative effect in the final risk. PMID- 2103066 TI - [The approach of accessibility in the planning of localization and size of health services]. AB - Geographical localization and size are two factors which play an important role in accessibility to health services. This accessibility, in its turn, is a basic requirement for ensuring the access of the population to health. A study was undertaken, in Santo Amaro, a suburb of the city of S. Paulo, Brazil, on the application of a methodology which takes into account the relationships among the geographical, demographic and social variables, in each particular situation, leading to the formulation of alternative proposals for the localization and size of health services. The kind of approach to each situation employed in this study proved fundamental in opening up a broad range of possibilities for the study of other subjects through the application of the same methodology, especially recommended for the implanting of local health systems. PMID- 2103067 TI - [Mortality among Japanese migrants residing in the municipality of Sao Paulo, Brazil, 1990]. AB - The mortality patterns of Japanese migrants (issei) and their descendants (nissei/sansei) resident in the City of S. Paulo, Brazil, are compared with those of their native country (Japan) and their place of adoption (S. Paulo), in 1980. The mortality data were obtained from death certificates for the issei and nissei/sansei populations and from official tabulations for deaths in Japan and S. Paulo. The population estimates were based upon the S. Paulo and Japanese censuses. The age-standardized populations were calculated according to the Jowett method. The five leading causes of death were basically the same for these populations under study. S. Paulo residents had the highest age-standardized mortality rates, except as regards deaths due to neoplasms, higher in Japan. The issei population (both sexes) presented intermediate values for deaths due to endocrine, nutritional, and metabolic diseases and diseases of the respiratory system; the female migrants also showed an intermediate rate for deaths due to diseases of the circulatory system. For the other causes, the lowest risk of dying was that registered for the issei population. The comparisons of the rates for cancers of stomach, breast, prostate, diabetes mellitus, ischaemic heart diseases, cerebrovascular diseases, homicide and suicide resulted in the detection of a possible transition experienced by the issei population, leading to the belief that the issei pattern of mortality is showing a deviation from the Japanese pattern and resembles that of S. Paulo. Since social and cultural changes are thought to be occurring among the migrants, one might argue that the role of environmental factors (including diet) is more important than the role of genetic factors in the incidence of and mortality due to these diseases. PMID- 2103068 TI - [Mortality among women in reproductive age in the municipality of Sao Paulo, Brazil, 1986. II. Deaths by maternal causes]. AB - In continuation to the research project on the accuracy of the certification of the underlying causes of death in women of child-bearing age (10-49), resident in the Municipality of S. Paulo, Brazil, in 1986, "original" death certificates were compared with "revised" death certificates (including additional information). The maternal mortality rate rose from 44.5 per 100,000 live births (l.b.) to 99.6 per 100,000 l.b., a high rate when compared with that of other places. When these data were compared with those of previous, similar investigations in the same city, the maternal mortality rate rose in the period 1962/4 through 1972/4 and fell in 1986. The main causes of death were: hypertension complicating pregnancy, other conditions of the mother which complicated pregnancy and puerperal complications. The need to extend the 42-day period related to the concept of maternal death, as well as the relationship between the non-maternal conditions (cancer, violence) and the gravidic-puerperal cycle are discussed. PMID- 2103069 TI - [Adolescent mortality in Brazil, 1977, 1980 and 1985. Magnitude and tendencies]. AB - Mortality among adolescents (10-19 yrs. of age), resident in 9 states of Brazil in 1977, 1980 and 1985, was analysed according to age (10-14 and 15-19 yrs. of age), sex (male, female) and underlying cause of death. The mortality was greater among males aged 15-19. External causes were responsible for the great mortality in all strata, mainly in the metropolitan regions of the urban southeast, rising throughout the period in these regions. The chronic diseases (cancer and cardiovascular diseases) were also frequent as the underlying cause of death in adolescents; though in much lesser proportion than the non-natural causes. PMID- 2103070 TI - [Analysis of the reliability of the declaration of cancer as the basic cause of death in Salvador, Brazil]. AB - The accuracy of the cancer mortality figures was determined by comparing the underlying causes of death as coded on death certificates with pathology reports and hospital diagnoses of a sample of 966 deaths of the total deaths occurring in Salvador during 1983. The death certificates were found to be accurate in 65% of 485 cancer deaths studied. Thirty-five histologically confirmed cancer deaths were found in a random sample of 481 deaths from other causes (460 stating other causes and 21 stating cancer sites that were not under study). This means that, approximately 700 more cancer deaths may be hidden among the remaining 10,098 death certificates. PMID- 2103071 TI - [Adolescence and contraception: 1. A study knowledge and use among women hospitalized for childbirth or abortion]. AB - A study of the knowledge and utilization of contraceptive methods by adolescent is presented. An analysis was carried out based on data collected from interviews with and recorded case histories of 78 puerperal adolescents (childbirth or abortion), assisted by an obstetric service in the county of Cotia, SP, Brazil, between May 1 and July 31, 1986. Of all the adolescents studied, 61.5% had some knowledge of contraceptive methods; the findings showed that such knowledge was influenced by factors such as: age, school background, parity and marital status. The main sources of information on contraception were: friends, relatives and partners, in this order; those least sought for in this regard were health professionals. Only one in each ten adolescents made use of some contraceptive measure, the most prevalent methods being the contraceptive pill, the Ogino Knauss method, condoms and coitus interruptus. In all of the cases of the utilization of these methods the same had been "recommended" by persons belonging to the adolescents' social group, and had been acquired in shops, without any health control. PMID- 2103073 TI - [Ethical-legal aspects of the civil responsibility of physicians in professional practice]. AB - The ethical-juridical concepts related to the civil responsibility of medical activity in liberal practice are brought up to date. To this end, the arguments which guide the shaping up of the contractual relationship between the physician and the client are analysed, as also are the foundations on which the notion of guilt--an essential component of civil responsibility, whether relating to technical acts of to those within the field of medical humanism--are grounded. The answers presented for the solution of this question by European juridical systems are given. PMID- 2103072 TI - [Evaluation of the ERA antirabies vaccine against antigenic variants of rabies virus in various post-immunization periods]. AB - Protection levels of an attenuated antirabies vaccine, of ERA origin, prepared in Kidney tissue culture, were evaluated in mice. Two schemes of vaccination were utilized: a single dose and 6 doses on alternate days. Animals of different experimental groups were challenged at 15, 30, 60 and 120 days postimmunization with six antigenic variants of rabies virus: strains of dog origin (S. Paulo, Brazil and Nigeria), vampire origin (DR-19 and Pernambuco, Brazil), fox origin (Rio Grande do Norte, Brazil), and CVS (Challenge Virus Standard). The results showed the effectiveness of the ERA vaccine against all antigenic variants of street and sylvatic rabies virus, independently of the vaccination scheme. Against the laboratory strains (DR-19 and CVS) the ERA vaccine was less effective, mainly in the groups vaccinated with a single dose. PMID- 2103074 TI - The engine or the caboose: health policy in developing countries. AB - A discussion of health policy in developing countries is presented. It argues that developing countries must adopt a progressive approach to health policy which rejects the two-tiered system of public and private health care. However, it also points out that ideology is not sufficient to maintain support. A progressive health system must utilize administrative and social and behavioral sciences to achieve effectiveness and efficiency in health care delivery. It cannot ignore these goals any more than a private health care system can. PMID- 2103076 TI - [General requirements in management of warm water whirlpool baths]. PMID- 2103075 TI - [Use of activated charcoal powder in water preparation for swimming pools--study of the introduction of adsorption technique with sand filters]. PMID- 2103077 TI - [The effect of vitamin E on the neurosecretory cells of the hypothalamus in white rats]. AB - For analysing the earlier detected hormone-depending effect of vitamin E (alpha TPh) on functional systems of the organism, a study was made of the influence of this vitamin on the morphometric indexes of functional conditions of supraoptic (SON), suprachiasmatic (SCN), paraventricular (NPV) and arcuate (AN) hypothalamic centres. Experiments were performed on Wistar rats (males and females) either of which was given per os a 5 mg daily dose of 5% D, L, alpha-tocopherol-acetate oil solution for three weeks. In results, a repression of functional activity of the neurosecretion cells (decrease in nuclear dimensions) was shown. Such an influence was found in all the centres studied except the SON which, on the contrary, was seen stimulated. Besides, considerable changes in nuclear and nucleolar dimensions were seen on histograms estimated by criterion lambda according to Kholmogorov and Smirnov. The results obtained can be possibly explained by differences in the initial levels of endogenic alpha-TPh and of other antioxidants in the cell membrane matrix of the hypothalamic centres, and, correspondingly, by different modulation effects of alpha-TPh exerted on the functional condition of neurosecretion cells. PMID- 2103078 TI - [The detection of the location in cattle chromosomes of a gene presumably determining testis development]. AB - The localization of the putative testis determining gene (TDF) was established with isotopic and nonisotopic methods of in situ hybridization in prometaphasic chromosomes of cattle. The results of both the methods were seen to coincide. The sites of hybridization have been revealed in X-chromosome (R-bands, q2.1 and q2.3.1). TDF was also localized in the proximal part of the long Y-chromosome arm. PMID- 2103079 TI - [Variants of chromosome compactization and the estimation of the capacity of mammalian oocytes for further development]. AB - The morphology of chromatin in spontaneously ovulated rat's oocytes was investigated. The degree of chromatin condensation was shown to vary widely: along with the typical cytological picture of metaphase II, both highly condensed (clamped) and decondensed ("not typical") forms of chromosomes were observed. A direct relation was discovered between the prevalence of the not typical morphological forms of oocyte chromosomes and the level of embryonal death. The shape of clamped and decondensed forms increased in the oocytes from old rats and in post-ovulatory aged oocytes. PMID- 2103080 TI - [A decrease in sister chromatid exchange frequency during the prolonged cultivation of human lymphocytes]. AB - Sister chromatid exchange (SCE) frequency at different times of fixation was studied in human lymphocyte cultures obtained from 6 donors. No differences were found in the SCE frequency between human lymphocyte cultures fixed at 72 and 96 hours of incubation (10.61 +/- 0.85 and 10.15 +/- 0.81 SCE per cell, respectively). However, a decreased SCE frequency (8.11 +/- 0.36 SCE per cell) was observed in cultures fixed at 120 hours of incubation. For a more detailed studies, one lymphocyte culture was fixed at different times of incubation (from 56 to 128 hours, at each a 8 hours). A slight increase in SCE frequencies was found at the interval between 56 and 88 hours of incubation, while starting from 104 hours of incubation a marked decrease in the SCE frequency was observed. Time dependent changes in the SCE frequency may be described by the equation y = 1.8614 + 0.3922x - (2.5183 x 10(-3))x2, where y is the number of SCEs per cell, and x--the duration of culture incubation in hours. The observed phenomenon may be associated with changes in proportion of T and B lymphocytes, or with heterochromatization of chromosomes during a prolonged cultivation, or with an early in vitro stimulation of the in vivo long-lived lymphocytes that may be more damaged than the in vivo short-lived and the in vitro late-stimulating ones. PMID- 2103081 TI - [Actin interaction with the plasma membrane fraction of the cells from a suspension subline of murine L fibroblasts]. AB - Effect of plasma membranes of murine fibroblasts cultivated in suspension on actin polymerization was studied. Using low shear viscometry of actin-membrane mixtures together with the number of extractions of membranes with actin depolymerizing buffers it was found that at least two polypeptides 220 and 94 kDa may be involved into the actin filaments-plasma membrane interaction. PMID- 2103082 TI - [Cytological research on the action of sodium thiosulfate on the process of induced acute pancreatitis in rats]. AB - The influence of sodium thiosulfate (STS) on the process of experimental acute pancreatitis (EAP) in rats was studied by cytomorphology, morphometry, autoradiography and cytophotometry. The influence was shown to vary at different stages of disease development. At the first stage ("primary effect" state) STS leads to the increase in the stability of exocrine pancreacytes (EP) against the toxins and to the decrease in the activity of proteases formed during necrobiosis. This results in the drop of the number of degrading EP and of the degree of inter- and intracellular oedema, and brings about shifts towards the normal values of the nucleus cytoplasm shapes, the nucleus/cytoplasm ratio, the EP population structure and their RNA and protein content. At the second stage STS stimulates DNA synthesis in EP and their proliferation leading to accelerated restoration of the number of viable cells. STS also stimulates the regeneration process hence preventing pancreatitis from passage to its chronic form. The mechanism of STS action of EP functions in normal cells and during pathogenesis is discussed. PMID- 2103083 TI - [The cytopathic and cytogenetic sequelae of chronic inhalational exposure to formaldehyde on female germ cells and bone marrow cells in rats]. AB - A study was made of cytopathological and cytogenetic effects of formaldehyde chronic inhalation, in doses 0.5 and 1.5 mg/m3, on the female rat's germ and marrow cells. The harmful effect of formaldehyde on germ cells (according to the patterns of early embryogenesis) is noted under the dose 1.5 mg/m3 only, while the reliable clastogenic and cytogenetic effects on the marrow cells were revealed even in the dose 0.5 mg/m3. It is concluded that the differences between effects of small doses of formaldehyde on different cell systems were evidently caused by the specific cell dynamics of these systems. PMID- 2103084 TI - [The effect of UV irradiation and of UV-irradiated autologous blood on the functional state of human peripheral blood lymphocytes]. AB - The effect of UV irradiation (UVI, 254 nm) and of UV-irradiated autologous blood on the spontaneous and mitogen-induced DNA-synthetic activity of intact lymphocytes has been studied. Lymphocytes were isolated from nonirradiated and irradiated blood, and from the mixture of UV-irradiated blood with the intact one in the volume ratio close to that in the blood stream during UV-irradiated blood autotransfusion (1:10, 1:40, 1:160). It has been shown that UVI of the whole blood caused in some donors the increase in spontaneous DNA synthesis, while in others the decrease or no statistically significant changes were observed. The analysis of the results obtained shows an inverse relation of the UVI effect to the initial level of spontaneous DNA synthesis (r = -0.68). In contrast to direct UVI effect, an addition of UV-irradiated blood to the autologous intact one resulted in an increase in spontaneous DNA synthesis in lymphocytes of all the samples examined. A 7-day cocultivation of lymphocytes, isolated from irradiated and nonirradiated blood samples, revealed a 1.8 times increase compared to the calculated value. The mitogen-induced DNA synthesis has a low sensitivity to UV rays, since the mitogens and the irradiation of optical range have presumably the common targets. It is assumed that photomodification of HLA-D/DR antigens can be a trigger mechanism for activation of immunocompetent cells by UVI. PMID- 2103085 TI - [The demonstration of proliferating cells by using monoclonal antibodies to 5 bromo-2'-deoxyuridine in the peroxidase-antiperoxidase method]. AB - Monoclonal antibodies (MAb) to the thymidine analog 5-bromo-2'-deoxyuridine (BrdUrd) and to horseradish peroxidase (HRPO) have been produced and characterized. On the basis of Mab to HRPO, complexes of the antibodies and HRPO (PAP-complexes) for immunochemical investigations are prepared. The possibility to identify proliferating cells in cultures of mouse myeloma Sp2/0 and mouse fibroblasts NIH 3T3 using Mab to BrdURd by the PAP-method is shown. The conditions of performing the analysis were optimized. The effect of various techniques ot cell fixation and cell DNA denaturation on cell morphology and on specific staining of nuclei of BrdUrd-containing cells in investigated. PMID- 2103086 TI - [Direct video-laryngoscopy]. AB - The combination of modern bivalved operative laryngoscopes, laryngeal telescopes and videotaping techniques has given us a new tool in the objective evaluation of organic laryngeal lesions. The purpose of the present study has been to describe a new method for direct video-laryngoscopy, an alternative to the classical Kleinsasser microlaryngoscopy technique, in diagnosis, clinical documentation and endolaryngeal microsurgery under video control without using an operating microscope. The direct video-laryngoscopy system consists of: a Weerda distending operating laryngoscope, Hopkins rod lens and Lumina telescopes (0 degrees, 25 degrees, 70 degrees or Mueller subglottoscope), an original telescope holder for a distending laryngoscope, a lightweight medical videocamera, a VHS videorecorder, laryngoscope holder and chest support. From November 1987 to May 1989, 370 patients with laryngeal lesions were examined and recorded. Only in 3 cases was the microlaryngoscopy technique used as it proved difficult to introduce the telescope into its holder because of patient anatomy: one short necked, obese patient, and two with a prominent tongue base and limited ability to open the mouth. In 367 cases direct video-laryngoscopy made careful diagnosis possible leaving a permanent record of the size and extent of the lesion. Such information could be used in accurate staging and follow-up. 320 patients were also treated by endolaryngeal microsurgery under video control without an operating microscope. Thanks to the width of the bivalved scope, the space for microsurgical instruments would be appreciably extended laterally, making it possible to better control the instruments on the monitor. The telescope lies on the superior spatula of the laryngoscope without interfering with the surgical procedures. The video material obtained was of high quality and of great value for diagnosis, pre- and post-operative evaluation, follow-up and documentation of various laryngeal disorders. PMID- 2103087 TI - [Posturography in unilateral peripheral vestibular deficiency]. AB - A thorough study of vestibular function cannot be limited to the evaluation of VOR alone; it must also include the study of VSR which serves to control erect stance under both static and dynamic conditions. In unilateral peripheral vestibular lesions (UVL) computerized stabilometry makes it possible to perform a more accurate evaluation of the VSR complex through the quantification of "postural sway". Furthermore, the diagnostic potential of stabilometry can be further fine-tuned by introducing a sensitization test, in particular the head retroflexion (OCR) and head shaking (OC-HST) tests. In the present study 61 patients with UVL of various etiology (viral, toxic, vascular, idiopathic) were studied. Besides electrooculography, stabilometry was performed under base conditions (eyes open and closed) and with sensitizing tests (OCR, OC-HST). L and S were used as statokinesigram parameters while frequency and oscillation amplitude on the sagittal and transverse planes were used as stabilogram parameters. Of the 61 UVL patients, 47.5% showed VOR compensation while static postural alterations were found in 31.1%; this raised to 50.8% when the sensitization test was introduced. Apparently the compensation phenomena became manifest more quickly for VOR than for VSR. The introduction of the sensitization test, however, markedly reduced this variance. The two sensitization, maneuvers used provided quantitatively equivalent results although in the absence of reciprocal agreement. Agreement was not even recorded between stabilometric HST and the head shaking test. This confirms the presence of two different routes for VOR and VSR. Nonetheless, the introduction of the sensitization test made it possible to identify those "false negative" VSR cases which were really pathological, thus making it possible to properly identify the patients' condition and arrange for adequate treatment. PMID- 2103088 TI - [Considerations on analysis time duration in a posturographic study in normal subjects]. AB - In order to evaluate the importance of analysis time on posturographic parameters (average X, Y and R, Sway Path, Sway Area, Ellipse Area) both with eyes open and closed, 24 normal subjects were examined for an overall period of 60 seconds. Mean +/- 1 SD values of each parameter were obtained for each time interval (0 20, 20-40, 40-60 sec.) into which the overall period was divided. With the eyes open, the parameters for each time interval did not differ significantly and they were always lower than those obtained with the eyes closed. On the other hand, with the eyes closed, there was a significant reduction in the various parameters as analysis time progressed. In 4 out of 24 subjects an inverse behaviour was detected. The authors conclude that the open-eye analysis time could be limited to 20 sec while, due to changes observed in the various posturographic parameters, closed-eye analysis time should be extended to 60 seconds. The analysis time may prove important in identifying peripheral or central vestibular pathologies since it may be that some of them induce earlier alterations of posturographic parameters while in other pathologies such changes are observed later on. PMID- 2103089 TI - [Histopathology of the internal ear: role of biopsy in ear neurosurgery]. AB - Ultrastructural evaluation is a tool which provides useful information which can lead to understanding of the different physio-pathological mechanisms involved in various otological disorders. After a short review of the procedures presently available for histopathology of human temporal bones from cadavers and indication of their related problem, the authors define the pros and cons of intra-operative biopsies of the membranous structures of the inner ear. The different histopathological methods are presented which may be applied on each specimen along with some technical details which make their use feasible for any otoneurosurgical center. The different membranous inner ear structures are taken into consideration; structures which can be approached by different otoneurosurgical procedures. Emphasis is placed on some technical hints to minimize artifacts. Finally, a more continuous, widespread use of intra-operative biopsies is proposed in order to obtain a fairly large amount of specimens as this would contribute to elucidate the unresolved problems inherent to many otological disorders. PMID- 2103090 TI - [The problem of the mandible in surgery of tonsillar tumors: proposal of a technique]. AB - The Authors report a technique of a conservative transmandibular approach for the surgical treatment of tonsillar region malignancies. The procedure is based upon the preparation of a vascular mandibular flap through two osteotomies, which are performed, the first above the mandibular foramen and the second below the mental foramen. The main advantages of present technique are: lip-chin-splitting is avoided and, due to the preservation of mandibular vascular and nervous supply, it is possible to accomplish, without risk, postoperative radiotherapy. Moreover, if dictated by oncologic reasons, this conservative procedure may easily be transformed into a radical surgery (commando or neck-jaw operation). PMID- 2103091 TI - [Three-quarter laryngectomy. Our experience: indications, surgical technique, results]. AB - Three-quarter laryngectomy is regarded as a supraglottic laryngectomy which has been extended on one side to the glottic plane. Indications are those for supraglottic laryngectomy at the vestibular level and of cordectomy extended to the arytenoid at the glottic level (undamaged lower paraglottic space, preserved motility). Surgical technique includes total removal of the laryngeal vestibule together with the hyoid bone, pre-epiglottic space and one supracricoid hemilarynx (vocal cord, arytenoid, medial wall of the entrance of the pyriform fossa) through an internal, subperichondrial approach. Reconstruction of a new cord on the hemilaryngectomy side is through a triangular strip of the exterior thyroid perichondrium. From 1975 to 1989 44 patients underwent a three-quarter laryngectomy in the authors' department. Functional results were positive in all cases. The oncological results were as follows: 6 recurrences (3 local, 2 locoregional lymph node recurrences and 1 distant metastasis) and 4 primary secondary tumors. 9 patients expired (6 of T, 2 of secondary tumor, 1 of other causes). The actuarial 5-year survival rate for the tumor was 79%. PMID- 2103092 TI - [Laryngocele: analysis of 18 cases and review of the literature]. AB - 18 cases of laryngocele (8 combined, 6 external, 4 internal) treated at the E.N.T. Clinic from January 1968 to December 1989 are reported. The review of the literature is specifically focussed on some controversial issues (i.e. nomenclature, association with laryngeal cancer, pre-operative work-up, surgical procedures). The main symptoms at presentation have proved to be airway obstruction (44.4%), hoarseness (44.4%) and a cervical mass (44.4%). In 12 cases (66.6%) surgical excision was performed by means of an extralaryngeal approach, median thyrotomy was used in 2 cases (11.1%). In 4 cases (22.2%) in which the laryngocele was associated with a laryngeal cancer, a total laryngectomy proved necessary, four patients required a second operation for a recurrence of the laryngocele. Major complications included pyocele (33.3%) and acute airway obstruction (22.2%). CT scan proved to be the most accurate radiological method for defining the spatial relationship between the laryngocele and the laryngeal structures and extralaryngeal soft tissues, in differentiating the laryngoceles from other cystic formations and in identifying the co-existence of a laryngeal cancer. Surgery is the treatment of choice. An extralaryngeal approach, according to Stell and Maran (1975) provides the most adequate exposure of the laryngocele, preserving the integrity of the laryngeal framework. Only in cases of small internal laryngoceles can endoscopic CO2 laser excision be considered a valid alternative. Tracheotomy is usually not indicated. PMID- 2103093 TI - [Monostotic fibrous dysplasia of the temporal bone: description of a case and review of the literature]. AB - Only a few cases of fibrous dysplasia of the temporal bone (monostotic form) have been described in the literature. The recent observation of a 15-year-old child presenting this pathology led the authors to review the literature available and to analyze the most common aspects of this disease. The clinical and radiological aspects, the differential diagnosis, histopathological features and therapeutical approaches are discussed. PMID- 2103094 TI - Revised nomenclature for coronavirus structural proteins, mRNAs and genes. PMID- 2103095 TI - The haemagglutinin of bovine coronavirus exhibits significant similarity to the haemagglutinin of type C influenza virus. PMID- 2103096 TI - Isolation and characterization of the acetylesterase of hemagglutinating encephalomyelitis virus (HEV). PMID- 2103097 TI - Differential reactivity of bovine coronavirus (BCV) and influenza C virus with N acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2)-containing receptors. PMID- 2103098 TI - Functional analysis of the coronavirus MHV-JHM surface glycoproteins in vaccinia virus recombinants. PMID- 2103099 TI - Background paper. Transcription and replication of coronavirus RNA: a 1989 update. PMID- 2103100 TI - Background paper. Aspects of coronavirus evolution. PMID- 2103101 TI - Analysis of different probe-labeling systems for detection by hybridization of bovine coronavirus. PMID- 2103102 TI - Comparison of the replication of distinct strains of human coronavirus OC43 in organotypic human colon cells (Caco-2) and mouse intestine. AB - Three strains of human coronavirus (HCV) OC43 were compared for their ability to cause enteric infections and to induce interferon alpha (IFN alpha) using the Caco-2 human colon carcinoma cell line which exhibits spontaneous epithelial differentiation in vitro. MRC-5 cell culture grown stocks were prepared from: 1. CV Paris, a strain of OC43 recovered from an outbreak of necrotizing enterocolitis in newborns. 2. CV Mb, a neurotropic strain of OC43 which exhibits strict neuronal specificity in murine neuronal cell cultures. 3. CV Rd, a strain of OC43 which grows to a high titer in human rhabdomyosarcoma (RD) cells. Immunofluorescent staining for nucleocapsid antigen and plaque assay in MRC-5 cells was used to detect viral replication. BG-9 (human foreskin) cells challenged with vesicular stomatitis virus were used to detect IFN alpha production by human peripheral blood monocytes (PBMC) stimulated by virus infected Caco-2 cells. Caco-2 cells infected with virus at a multiplicity of infection of 0.5 yielded 10(4.6) and 10(4.4) plaque forming units/ml (pfu/ml) with CV Rd and CV Paris respectively, while CV Mb yielded only 10(3) pfu/ml. Caco 2 cells infected with CV Rd induced 64 IU/ml of IFN alpha in PBMC while these cells infected with CV Paris induced less than 2 IU/ml IFN alpha. In cells infected with CV Mb 4 IU/ml IFN alpha was detected. The results suggest that a lack of IFN alpha induction by CV Paris may be an indicator of its enteropathogenic potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103103 TI - Background paper: functions of coronavirus glycoproteins. PMID- 2103104 TI - Detection of coronavirus RNA in CNS tissue of multiple sclerosis and control patients. PMID- 2103105 TI - Molecular characterization of the 229E strain of human coronavirus. AB - Human coronaviruses (HCV) cause various respiratory, gastrointestinal and possibly neurological disorders. Very little is known of the molecular biology of these ubiquitous pathogens. We have undertaken the molecular characterization of the prototype 229E strain of HCV. The virus grew to the highest titers on a human embryonic lung cell line (L132) at 33 degrees C and purification was optimal on Renografin-60 gradients. Metabolic labeling with [35S]methionine or [3H]glucosamine or galactose and analysis by SDS-PAGE revealed at least five structural proteins, which could be identified by analogy with murine coronaviruses as follows: the spike glycoprotein (E2/S), in both monomeric (88-97 kDa) and dimeric (190-200) forms, the nucleoprotein (N) at 52-53 kDa and the matrix protein (E1/M), in both glycosylated (25-26 kDa) and non-glycosylated (20 22 kDa) forms. Monomeric, dimeric and multimeric (greater than 200 kDa) forms of E2/S incorporated glucosamine and galactose, whereas only galactose was incorporated into E1/M. Multimers of E1/M, with apparent molecular masses of 44, 74 and 140 kDa, were formed in the absence of a reducing agent. PMID- 2103107 TI - Background paper. Coronavirus M and HE: two peculiar glycoproteins. PMID- 2103106 TI - Biosynthesis and function of the coronavirus spike protein. PMID- 2103108 TI - Structure and expression of the bovine coronavirus hemagglutinin protein. PMID- 2103109 TI - Host-parasitoid associations in patchy environments. AB - Studies of insect host-parasitoid interactions have contributed much to the consensus that spatial patchiness is important in the regulation of natural populations. A variety of theoretical models predict that host and parasitoid populations, although unstable in the absence of environmental heterogeneity, may persist at roughly steady overall densities in a patchy environment owing to variation in levels of parasitism from patch to patch. Observed patterns of parasitism, however, have a variety of forms (with variation in attack rates among patches depending directly or indirectly on host density, or showing variation uncorrelated with host density). There is some confusion about the dynamical consequences of these different forms. Here we first show how the dynamical effects of all these forms of environmental heterogeneity can be assessed by a common criterion. This 'CV2 greater than 1 rule' states that the overall population densities will remain roughly steady from generation to generation if the coefficient of variation squared (CV2) of the density of searching parasitoids in the vicinity of each host exceeds approximately unity. By partitioning CV2 into components, we show that both direct and inverse patterns of dependence on host density, and density-independent patterns, all contribute to population regulation in the same way. Second, we show how a maximum-likelihood method can be applied to the kind of field data that are usually available (that is, percentage parasitism versus local host density) to estimate the components of CV2. This analysis indicates that heterogeneity is large enough to stabilize dynamics in 9 of 34 published studies, and that density independent heterogeneity is the main factor in most cases. PMID- 2103110 TI - Unacceptable risk. PMID- 2103111 TI - Corticosteroids for Pneumocystis pneumonia. PMID- 2103112 TI - Round table: postterm pregnancy. Our moment with Courtney. PMID- 2103113 TI - Measuring symptom severity and treatment outcome of temporomandibular disorders with the TMJ scale: case report. PMID- 2103114 TI - Sequencing and integration of periodontal, prosthodontic and implant therapies (the concept of "jumping" cases). PMID- 2103115 TI - Osteointegrated implants in a microvascular graft to restore a subtotal mandibulectomy--case report. PMID- 2103116 TI - A preliminary clinical evaluation of the Steri-Oss implant system. PMID- 2103117 TI - Predictable mandibular nerve location--a clinical zone of safety. PMID- 2103118 TI - Success criteria in oral implantology. A review of the literature. PMID- 2103119 TI - Repair of periodontal bone defect with hydroxylapatite implants. PMID- 2103120 TI - Screw-shaped hydroxyapatite plasma sprayed implants. PMID- 2103121 TI - Predoctoral curriculum guidelines in implant dentistry. PMID- 2103122 TI - Implantology progresses into the 1990's. A personal view of compassion versus components. PMID- 2103123 TI - Divisions of available bone in implant dentistry. PMID- 2103124 TI - Enamel microabrasion to improve enamel surface texture. AB - Enamel microabrasion is effective in removing superficial enamel coloration defects. The technique has now also been shown to improve the appearance of enamel with surface texture irregularities. The method of microabrading teeth with surface texture defects is described, and several cases are documented. PMID- 2103125 TI - Light-cured resin cements for cementation of esthetic restorations. PMID- 2103126 TI - Influence of finishing technique on microleakage. AB - Four different finishing techniques were used in a dentin bonding agent/composite resin restoration to evaluate the possible influence of finishing technique on microleakage. Results indicated that finishing technique affects the ability of the restorative system to resist microleakage. Under the conditions of this study, best results were achieved with a 30-fluted bur followed by a short wet polish. Samples finished dry with polishing disks demonstrated considerable microleakage. This study also suggests that homogeneous nonagglomerated microfilled composite resin does not require disk finishing. PMID- 2103127 TI - Evaluation of microleakage in tenure-based restorations. AB - This study evaluates the effects of six composite resins, which use three different curing systems, on the ability of Tenure to resist microleakage. The curing systems were a photoinitiated dual-cure system, a dual-cure system, and light-cure systems. A total of 39 human molars were used. Following 2,000 cycles on a thermocycler, specimens were exposed to 0.2 percent basic fuchsin dye for 24 hours and then examined for microleakage. Results indicated that the composite resin plays an important role in the ability of a restorative system to resist microleakage. The photoinitiated dual-cure system produced significantly less microleakage than light-activated systems. No difference in microleakage was found between light-activated systems and the dual-cure system. PMID- 2103129 TI - Update on tooth whitening systems. PMID- 2103128 TI - An all porcelain lingual bonded retainer: a case study. AB - In recent years, resin bonded metal retainers have been used to replace teeth in a conservative manner. In addition, porcelain laminates or veneers have been used in esthetic dentistry on single teeth in areas that previously dictated reductions of tooth structure. This paper describes a method of replacing a missing lower anterior tooth with an all porcelain bonded retainer. PMID- 2103130 TI - Protecting the eye from ultraviolet A radiation during photochemotherapy. AB - Except for the skin, the eye is the only organ that is continuously exposed to solar radiation, including longwave ultraviolet irradiation (UVA). Since 8 methoxypsoralen (8-MOP) remains not only in the skin but also in the lens of the eye after 8-MOP + UVA (PUVA) treatment, wearing protective goggles just during the UVA irradiation is insufficient. It is wise to shield the eyes for several hours after 8-MOP ingestion, to avoid or reduce possible long-term side effects such as cataract formation. Adequate eye protection from UVA after PUVA can be provided by sunglasses that filter out the appropriate UVA spectrum from the sunlight. Nearly all the commercially available sunglasses are colored, which reduces the intensity of the visible light reaching the eye. In such cases, the diameter of the pupil can remain dilated, which it would not without sunglasses. However, the UVA intensity remains the same. As a result, more UVA can reach the lens. In this study, new uncolored glasses are evaluated and compared with commercially available sunglasses (all colored) to determine their UVA transmission. PMID- 2103131 TI - A quantitative study of the interaction of ultraviolet A and ultraviolet B in producing delayed pigmentation. AB - The interaction of ultraviolet A (UVA) and UVB in producing delayed pigmentation was quantitatively studied on the backs of 19 healthy Japanese subjects. The minimal pigementation dose for UVA (MPDA) and UVB (MPDB) was first determined using narrow-band radiation of 360 nm and 290 nm respectively. The average MPDA and MPDB was 16.4 J/cm2 and 32.9 mJ/cm2 respectively. In experiment 1, fractional doses of 0.2, 0.4, 0.6 and 0.8 MPDA were first irradiated on 4 sites each. Immediately following each exposure, fractional doses of either 0.2, 0.4, 0.6 or 0.8 MPDB were superimposed on the same sites, resulting in each exposure site receiving a different combination of fractions of MPDA and MPDB (A + B). This was repeated with the sequence of exposure reversed (B + A). The results demonstrated that the wavelengths interacted via photoaddition in producing delayed pigmentation, irrespective of the order of exposure. When a 3-h time interval was allowed between exposures in experiment 2, there was again no evidence of deviation from photoaddition with either order of exposure. This study shows that subthreshold doses of UVA and UVB interact additively in the production of delayed pigmentation. PMID- 2103132 TI - Noninvasive computerized analysis of skin chromophores in vivo by reflectance spectroscopy. AB - Reflectance spectroscopy in an objective and accurate method for determining skin colour and has been widely used for measuring physiological variations in skin colour and for monitoring dermatological treatment modalities. Previous studies have used pigment indexes to describe changes in skin colour. Using a multiple regression method to calculate reflectance spectroscopic data, it has been possible to calculate the relative amounts of the different chromophores present in the skin. The technique was found reliable in in vitro tests and in experimentally induced variations in pigment content caused by venous congestion or ultraviolet (UV) light irradiation. In developing UV-induced erythema, the primary events seem to be venous dilatation followed by an increase in blood flow. PMID- 2103133 TI - Ultraviolet B light-induced alterations in epidermal Langerhans cells are mediated in part by tumor necrosis factor-alpha. AB - Acute, low-dose treatment of murine skin with ultraviolet B light (UVB) impairs the induction of contact hypersensitivity to dinitrofluorobenzene, and depletes the epidermis of normally appearing class II MHC positive Langerhans cells. Recent studies with inbred strains of mice have revealed that impairment of contact hypersensitivity by UVB is a polymorphic trait that is polygenically dictated by susceptibility alleles at the Lps and Tnf alpha loci. Since impairment of contact hypersensitivity by UVB has been associated with deleterious effects on Langerhans cells, we have tested the hypotheses that UVB and TNF alpha have similar effects on epidermal Langerhans cells and that TNF alpha is an important mediator of this UVB-induced effect. Our results confirm that both UVB and TNF alpha reduce the density of class II MHC-bearing epidermal cells and alter the morphology (shortened or absent dendrites, rounded shape) of the cells that remain. UVB- and TNF alpha-induced changes are prevented by systemic administration of neutralizing anti-TNF alpha antibodies. Circumstantial evidence, based on time of onset of numerical and morphologic changes among Langerhans cells following epidermal treatment, suggests that TNF alpha is the mediator of UVB-induced changes. Moreover, the ability of intradermally injected TNF alpha to alter Langerhans cells depends, in part, on whether the strain of mouse is of the UVB-susceptible or UVB-resistant phenotype as it pertains to the effect of UVB on contact hypersensitivity. PMID- 2103134 TI - An ultrastructural study of human epidermal Langerhans cells irradiated with grenz rays and ultraviolet A. PMID- 2103136 TI - Clinical transplants 1990. PMID- 2103135 TI - The UNOS Scientific Renal Transplant Registry--1990. AB - Based upon data reported to the UNOS Scientific Renal Transplant Registry between October 1987 and October 1990: 1. One-year graft survival rates were 78% for 14,203 recipients of first cadaver donor transplants, 70% for 2180 recipients of second cadaver transplants, and 59% for 487 recipients of third or fourth transplants. First transplants from living donors had 90% 1-year graft survival. 2. One-year graft survival was 75% for 2,273 Black recipients of first cadaver transplants and ranged between 79-80% for recipients of other races (p less than 0.001). 3. Broadly sensitized (50% peak PRA) first cadaver transplant recipients had 77% 1-year graft survival versus 79% for nonsensitized or narrowly sensitized recipients. Cadaver retransplant recipients with greater than 10% peak PRA had 65% 1-year graft survival while those transplanted with no antibody had 78% (p less than 0.001). Survival of nonsensitized retransplanted patients was not significantly less than first transplant recipients. 4. Graft survival was 78% at 1 year for both male and female recipients of first cadaver donor transplants. Retransplanted females had significantly higher 1-year graft survival at 70% than males at 67% (p less than 0.01). Male donor kidneys had significantly higher survival rates than female donor kidneys in both first and retransplanted patients. One-year graft survival was 79% and 70% with male donors and 75% and 65% with female donors in first and retransplants, respectively (p less than 0.01). 5. Pediatric recipients (under 16) and older recipients (over 60) of first cadaver transplants had 73% 1-year graft survival compared to 78-79% for those aged 16-60. 6. Among recipients of first cadaver transplants, 1-year graft survival rates varied over a 20% range with the age of the donor. Excluding pediatric and older patients, the best survival rates (81%) were obtained with kidneys from donors aged 16-45. Kidneys from younger and older donors yielded progressively poorer results. The lowest survival was with 181 donors aged 1-5 (60%) and 145 donors over 60 (69%). 7. One-year graft survival was 85% for 274 recipients of 0 HLA-A,B,DR-mismatched first cadaver transplants and 74% for 717 recipients of transplants mismatched for 6 HLA-A,B,DR antigens. Graft survival progressively declined with increasing histoincompatibility. 8. One-year graft survival decreased by 20% if the kidney failed to produce urine in the first hour, from 80-60% in first transplant recipients and from 72-50% in retransplanted patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2103137 TI - Cardiac transplantation: the UCLA experience 1984 to 1990. AB - The international experience has documented the therapeutic value of cardiac transplantation in the management of carefully selected patients with endstage heart disease. The UCLA program's experience over the years 1984 to 1990 mirrors these results, establishing heart transplantation as an accepted form of therapy that offers extended survival and improved quality of life compared to alternative means of treatment. Criteria of eligibility for recipient candidates have become less restrictive, most notably the expansion of age limits to include increasingly older patients. Seventy-three patients over 55 years of age underwent heart transplantation in this series, with actuarial survival results comparable to that achieved in adult patients 55 years of age and under (68.5% vs 74.7% at 4 years, respectively). Twenty-one children between the ages of 7 months and 17 years have undergone cardiac transplantation at UCLA with survival results comparable to that of our adult population (74.3% vs 76.5% actuarial survival at 3 years, respectively). Continued efforts aimed at the development of improved means of immunosuppression as well as better methods for the detection of rejection are needed if these results are to be significantly improved. PMID- 2103138 TI - Liver transplantation in the United States: 1988 to 1989. AB - Orthotopic liver transplantation was performed more often in 1989 than in 1988. This procedure was performed at 57 institutions in 1988 and at 64 in 1989. Among the 53 institutions in which OLTX was performed in both years, the tendency was to increase volume. Volume in 1988 was not an indicator for volume increase or decrease in the next year. For example, about 60% of the centers which performed 5-9 OLTXs in 1988 had a greater volume in 1989. This was similar to the percentage among centers which performed 30-49 OLTXs in 1988. Only centers which performed at least 100 OLTXs in 1988 increased in volume uniformly (3 centers). There was about a 25% increase in the number of OLTX recipients, and the characteristics of the recipient population changed. In 1989, as compared to 1988, there was a larger proportion of recipients over age 40 with a concomitant proportionate decrease in pediatric recipients. Indications for OLTX were also different. In 1988, biliary atresia and primary biliary cirrhosis were the major diagnoses for which OLTX was performed. In 1989, however, alcoholic cirrhosis was the most prevalent diagnosis among OLTX recipients, accounting for more than 1 of every 7 procedures. We also found that the distribution of UNOS description changed. Significantly more recipients were classified in the best functional group, and significantly more recipients were on life support in 1989 compared to 1988. Whether this reflects a change in the actual functional status of recipients, or change in the management of these patients, is a topic for further research.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103139 TI - Experience with partial liver transplantation in Hannover. AB - Within a 7-year period 37 PLTx have been performed in 32 patients (25 children, 7 adults). Age at the time of operation was 5 years in two-thirds of all cases (23 of 37). Indications were elective in 17 patients and urgent in 20. The following types of PLTx were used: a LLL in 24 cases, a LL in 9, and a RL in 4. Three donor livers were split and transplanted into 2 recipients each. The body weight ratio between donors and recipients ranged from 0.9:1 to 12.3:1. Nineteen of 26 adult donor livers were transplanted into pediatric recipients. Patient and graft survival following elective PLTx at 2 years was 69.7% and 50.5%, respectively, which was not significantly different from the results following urgent transplantation. Overall, 30-day mortality was 18.8% (6 of 32 patients) and was relative to the patients' clinical status at the time of transplantation. Graft loss in 29.7% (11 of 37 transplants) was due to liver-related causes such as chronic rejection (n = 5) and primary nonfunction (n = 4). Postoperative surgical complications were noted in 13 cases but were not different from those seen with WLTx. At present, 19 of 32 recipients (59.4%) are alive between 1 and 43 months following transplantation. PMID- 2103140 TI - Liver transplantation: an Australian experience. AB - During a 4 and a half-year experience, 283 patients were referred to the Australian National Liver Transplant Unit. Sixty (21%) were children. The major causes of liver failure in the adults were chronic active hepatitis (27%), primary biliary cirrhosis (13%), primary sclerosing cholangitis (12%), fulminant hepatic failure (9%), alcoholic cirrhosis (9%), and malignancy (9%). In the children they were biliary atresia (43%) and inborn errors of metabolism (18%). One hundred and ninety-seven (69%) were accepted for liver transplantation. Of 111 (39%) accepted for early transplantation, 18 (16%) died before a donor became available. There were 319 possible organ donors. Ninety patients (24 of them children) received 100 grafts. Sixty-three (70%) patients survived. For all recipients, 1-year survival was 73%. Two-, 3- and 4-year survivals were 67%. One- to 4-year survivals for adults with benign conditions were 76%, contrasting with results for those with hepatic malignancy (20% 1-year survival). Children weighing greater than 8 kg did well whether they received whole grafts (80% 1- to 4-year survival) or reduced grafts (75% 1- to 4-year survival). Infants weighing less than 8 kg who received reduced adult grafts did significantly worse (20% 1- to 4-year survival). All 8 (100%) patients with fulminant hepatic failure who received grafts survived, including 3 who received ABO-incompatible grafts, though 2 of these subsequently required retransplantation. Rehabilitation of survivors was excellent with 91% of adults and 94% of children pursuing normal activities. Only 2 (2%) grafts failed with primary nonfunction, both in infants because of infarction. Graft survival was significantly worse (p less than 0.01) in patients with a positive direct crossmatch test against the donor. We calculate that the need for liver transplantation in Australia is approximately 7 per million of population per year. Increased donor offers are required to avoid deaths of patients on the waiting list. Reduced-size adult livers are successful for children and have alleviated considerably the critical shortage of pediatric donor livers. Liver transplantation is a highly satisfactory treatment for patients with benign liver disorders but not for those with malignant conditions. Patients with fulminant hepatic failure not responding to conservative therapy should be treated by liver transplantation. In this and other urgent circumstances, an ABO-incompatible liver may be lifesaving though retransplantation with an ABO-compatible liver may subsequently be required. The results of liver transplantation for nonmalignant conditions have improved steadily with clinical experience, with 1- and 2-year patient survivals during the past 28 months of 85%. PMID- 2103141 TI - Bone marrow transplantation for hematologic malignancies: the Stanford experience. AB - Allogeneic and autologous BMTs are highly effective and successful treatment modalities for selected patients. Use of BMT earlier in the course of disease yields better results when compared to patients with more advanced disease. Recent advances such as use of cloned growth factors, cytokines, etc..., will continue to contribute to lessen morbidity and mortality. Finally, as investigators understand, prevent, and treat expected side effects from BMTs, the patients' burden in terms of physical, psychological, and financial costs should lessen substantially. PMID- 2103142 TI - Bone marrow transplantation--the Marsden experience. AB - Leukemic relapse remains a major problem after both autologous and allogeneic transplantation. In the single-arm ALL autograft study our results were very encouraging and suggest that Melph/TBI can produce disease-free survival results at least as good as with other conditioning regimens. The role of postautograft maintenance remains unclear, but we feel our results are sufficiently encouraging to justify a randomized study, particularly as we studied a group of patients with relatively poor prognoses. In our study comparing Cy and TBI with Melph and TBI in AML, we have shown a significant increase in antileukemic activity after transplantation following the latter conditioning regimen. The retrospective study of Melph/TBI in autologous versus allogenic transplantation suggested that in AML this antileukemic effect may derive from increased GvHD and is not present in the autologous setting. We hope that by increasing the intensity of our GvHD prophylaxis we can reduce the toxicity of Melph/TBI and preserve its antileukemia effect. Our experience with GM-CSF has been a little disappointing: despite facilitating neutrophil recovery, we were unable to demonstrate a clinical benefit in the treatment arm. We hope to further investigate the use of cytokine combinations in the transplant setting. PMID- 2103143 TI - Allogeneic bone marrow transplantations at Huddinge Hospital and strategies to improve survival. AB - At Huddinge Hospital 275 patients underwent allogeneic bone marrow transplantation. Among children in first remission of acute leukemia or chronic phase CML (early leukemia), with HLA-identical marrow the 8-year leukemia-free survival was 77%. This was better than 38% in children undergoing transplantation in second to fourth remission (p less than 0.0009). In adults with early leukemia, the 8-year leukemia-free survival was 47% compared to 21% for intermediate-risk adults (p = 0.007). Among 25 patients with severe aplastic anemia receiving marrow from HLA-identical siblings, the actuarial 10-year survival was 78%. In 14 patients with various metabolic disorders, of whom half received marrow from HLA-mismatched donors, the actuarial 7-year survival was 71%. Forty-three patients were given marrow from HLA-mismatched donors and had an increased incidence of acute graft-versus-host disease (GvHD) and death due to GvHD compared to recipients of HLA-identical bone marrow. The major causes of death among our patients were relapse of leukemia, death due to GvHD, cytomegalovirus (CMV) pneumonitis, bacterial infection and invasive fungal infections. By preventing GvHD with T-cell depletion or methotrexate (MTX) combined with cyclosporine (CsA) acute GvHD decreased, but the incidence of relapse increased compared to patients treated with MTX or CsA alone. This resulted in improved survival in patients older than 30 years, but a nonsignificant decrease in leukemia-free survival in younger patients. There was an association between herpes virus immunity in the recipient and GvHD. CMV pneumonitis increased following GvHD and decreased in patients treated with MTX combined with CsA. Invasive fungal infections may be treated or prevented using amphotericin B encapsulated in liposomes with few side effects. PMID- 2103144 TI - Pancreatic transplantation using enteric exocrine diversion: the Stockholm experience with 117 cases. AB - One-hundred twenty-eight pancreatic transplantations were performed between 1974 and 1990; 117 of which were with pancreatico-enterostomy. Combined renal and pancreatic transplantations were performed in 68 uremic patients and in 8 preuremic recipients. Single pancreatic transplantations were performed in 31 recipients and in 6 instances, the pancreatic transplantation was performed in a patient who already had a renal graft. In 4 consecutive series (n = 15, 20, 21, 11) of combined transplantations in uremic diabetic patients, the 1-year graft survival rate has excessively improved markedly (27%, 65%, 68%, and 73%). In 3 similar series of single pancreatic transplantations (n = 7, 13, 6) the results also improved, but still remained inferior (0%, 33%, and 33%). In 42 patients followed for more than 1 year after transplantation, the mean blood glucose tolerance test 4.2 +/- 0.5, HbA1c 5.1 +/- 0.8, 2-hour blood glucose level of the oral glucose tolerance test 6.9 +/- 2.1 and the K-value of the intravenous glucose tolerance test 1.2 +/- 0.6%. The results with pancreatic transplantation with pancreatico-enterostomy are now satisfactory. However, immunological graft losses still constitute a major problem in the non- or preuremic recipients. PMID- 2103145 TI - The role of transplantation in diabetics with end-stage renal disease. AB - At our center, KPT is the treatment of choice for diabetics with ESRD who are not irreversibly disabled by their secondary complications of diabetes. Mortality, as a result of cardiovascular complications, has a significant impact on the outcome of patients in both the KPT and KTA groups. Metabolic complications are problematic in the early posttransplant period. Infectious complications are frequent but not life threatening in the combined recipients. Excellent graft outcome (pancreas and kidney) can be achieved in those patients selected to undergo the KPT procedure. PMID- 2103146 TI - The Registry of the International Society for Heart Transplantation. AB - As of October 1990, the Registry of the International Society for Heart Transplantation has received data on over 14,000 heart and over 1,100 combined heart-lung or lung transplant recipients from over 200 centers worldwide. While the areas of single-lung transplantation and pediatric heart transplantation continue to expand rapidly, further growth in annual numbers of cardiac and pulmonary transplant procedures is now limited by donor supply. Operative mortality and late survival have improved during the past decade, however, infection and rejection continue to be the main causes of death. As the number of long-term survivors continues to increase, chronic rejection remains the major obstacle and results with retransplantation have not been very encouraging. PMID- 2103147 TI - Lessons learned and future hopes: three thousand renal transplants at the University of Minnesota. AB - 1. The experience of 3,183 transplants between June 7, 1963 and September 30, 1990 at the University of Minnesota was reviewed. 2. Patients were divided into 4 historical periods-each era was associated with improved outcome. 3. As results have improved, the proportion of patients less than 5 years old and the proportion greater than 50 years old have increased. Type I diabetes has become the most common cause of renal failure in patients transplanted here. 4. The most important variable leading to improved outcome was donor source. Both HLA identical and HLA-nonidentical LRD transplants have better outcome than CAD transplants (p less than 0.0001). 5. Multivariate analyses were done to determine risk factors for survival: a) in the first year, and b) in subsequent years. In the first year, age greater than 50, diabetes, and retransplantation had an adverse affect whereas LRDs and CsA immunosuppression were beneficial. Similar factors affected survival after the first year. HLA mismatch had no impact. 6. When death with graft function was excluded, diabetes and age greater than 50 were no longer risk factors, suggesting that the excess graft loss in these groups was due to patient death. 7. Chronic rejection and death with function remain the predominant causes of graft loss. 8. As protocols have evolved, results have improved, and previously "high-risk" patients are being successfully transplanted. Future efforts should be directed at decreasing graft loss from rejection and death with function. PMID- 2103148 TI - Experience with renal transplantation in the second and third decades at the Hennepin County Medical Center. AB - Approximately one-third of the patients receiving renal transplants have functioning allografts at 10 years. Chronic rejection continues to be the leading cause of kidney loss in late survivors. Atherosclerotic cardiovascular disease, liver failure, malignancy, and sepsis are the major causes of late death. Identification and control of the risk factors contributing to patient mortality should enhance the long-term success of renal transplantation. PMID- 2103149 TI - Living-unrelated renal transplantation at the University of Wisconsin. AB - 1. Use of LUrDs under a DST protocol results in a 70% actuarial graft survival at 6 years which is not statistically different from haploidentical or primary cadaver recipients transplanted over the same time period. 2. Sensitization is common, despite the use of Aza, especially in husband-to-wife donor-to-recipient relationship. 3. Rejection occurs frequently, despite the use of DST, however, it is usually reversible. The high rejection rate did not influence the quality of long-term graft survival with very few patients losing grafts to chronic rejection. 4. Expansion of the use of LUrDs could help provide additional organs for transplantation. PMID- 2103150 TI - 1,000 renal transplants at the Massachusetts General Hospital: improved allograft survival for high-risk patients without regard to HLA matching. AB - Excellent allograft survival is now routinely accomplished following renal transplantation. Changes in immunosuppression have resulted in a significant improvement in early survival for recipients of primary LRD and CD allografts. In our series, crossmatching techniques which accurately assess alloantibody reactivity and not the degree of HLA mismatch have also permitted successful transplantation of such high-risk groups as recipients of second transplants and highly sensitized recipients. However, a yearly attrition rate of allograft loss persists for all recipients. These long-term observations stress the need for newer approaches to immunosuppression in the future, which include protocols that allow for an indefinite tolerance to incompatible donor antigens. PMID- 2103151 TI - Kidney transplantation at UCLA. AB - 1. Six hundred twenty kidney transplants have been performed at UCLA since 1984. Rather than 1 rigid immune suppression protocol for all patients, an individualized approach has been taken since the advent of OKT3 in 1987. Since then, the 1-year cadaver graft and patient survival rates have been 87% and 97%, respectively, for both primary and repeat transplants, including various categories of high-risk recipients. 2. Delayed graft function, HLA matching, and percent prior sensitization were major determinants of graft survival. Race, age, and diabetes were not significant determinants of graft outcome. 3. Small children had a 94% 1-year graft survival rate following cadaver transplantation. Sequential immune suppression, the use of large kidneys, and careful perioperative fluid management to prevent graft thrombosis may be responsible for the graft survival rate. 4. Long-term (1 year) results continue to show deterioration in graft survival. Many patients are hypertensive and hypercholesterolemic. Many children are noncompliant with medications. PMID- 2103152 TI - Donor antigen-specific immunosuppression in cadaveric and living-related donor kidney allograft recipients. AB - This is a review of the University of Alabama Hospital's clinical experience with 1-haplotype-mismatched LRD renal transplants, utilizing a stored-blood DST protocol and with cadaveric renal transplants utilizing DBM transfusion. Stored blood DST does not significantly improve LRD allograft survival either in Aza-, P , or CsA-treated patients, although there is a trend toward better survival in Aza/DST versus Aza/no-DST recipients (78% vs 84% 12-month allograft function). Importantly, although the early acute phase graft loss was slightly diminished by DST, the late phase loss (slope of curve) was essentially identical to nontransfused patients. Thus, we cannot demonstrate a beneficial effect by the use of DST in achieving improved long-term graft survival in recipients of 1 haplotype-matched recipients. The use of cryopreserved DBM transfusions in cadaveric allograft recipients, however, has resulted in significantly improved survival compared to control patients who received the marrow donor's contralateral kidney and similar immunosuppression without marrow infusion [92% vs 73% (p = 0.01)]. DBM-transfused patients demonstrate diminished donor-specific responsiveness in MLC compared with controls. P withdrawal can be accomplished safely in the majority of marrow recipients; however, this has not been tested in the controls. Donor-nucleated cells persist in the peripheral blood of some DBM transfused patients for at least 2 years following transplantation. Presently, the significance of persistent chimerism in these patients with respect to donor responsiveness and allograft tolerance is unclear. PMID- 2103153 TI - Pancreas transplantation: report on United States results from United Network for Organ Sharing Registry with comparison to non-United States results from the International Registry. AB - From December 17, 1966 to December 31, 1990, 3,069 pancreas transplants worldwide (1,806 United States and 1,263 non-United States) were reported to the International Pancreas Transplant Registry, including 606 in 1990. The 2,871 pancreas transplants in the Registry data base as of October 31, 1990 were analyzed. Results worldwide improved in each of 5 successive eras. The recipient and pancreas graft functional survival rates at 1 year for all 1988 to 1990 cases (n = 1,415) were 91% and 68%, respectively. The effect of multiple variables on outcome was determined by analyzing the 2,037 cases in the International Registry data base since 1985. Worldwide, BD (n = 1,566) was used more frequently than DI (n = 327) or ED (n = 174) and was associated with a significantly higher (p less than 0.001) graft functional survival rate, at 1 year 65% versus 56% and 53%, respectively. Worldwide, SPK transplants (n = 1,644) were performed much more frequently than either PAK (n = 223), or PTA (n = 212). The pancreas graft functional survival rate was significantly higher (p less than 0.001) in the SPK than in the other 2 categories, at 1 year being 68% versus 45% and 37%, respectively. The kidney graft survival rate for all SPK cases at 1 year was 80%. Worldwide, a significant effect of HLA-DR matching was seen only in analysis of PTA, graft survival at 1 year being 54% in PTA recipients matched for 2 DR antigens (n = 13), 44% for 1 DR antigen (n = 63) and 29% for 0 DR antigens (n = 97) (p = 0,015 for 2 vs 0 DR). Worldwide, more than half of the pancreas grafts were preserved in UW solution (n = 1,111), and an increasing preservation length was not associated with a significant decrease in functional survival rates, at 1 year being 67%, 73%, 71%, and 60% for those stored less than 12 (n = 563), 12-24 (n = 416), 24-30 (n = 30), and greater than 30 (n = 5) hours. A separate analysis was performed on pancreas transplants in the United States reported to the UNOS Registry from its inception on October 1, 1987 to October 21, 1990 (n = 1,021). Almost all pancreas transplants in the United States during this period were by the BD technique (92%). The overall patient and pancreas graft survival rates were 92% and 72% at 1 year.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2103154 TI - Effect of positive crossmatch against donor B lymphocytes in kidney transplantation: a prospective one-center study. AB - Circulating antibodies reacting with donor lymphocytes, increasingly found in patients awaiting a kidney graft, are a cause of transplantation delays. Some of these antibodies may not be detrimental to the graft, and their recognition could be beneficial for the treatment of immunized patients. In this chapter, we report on a prospective study of 138 cases of kidney transplantation performed against a positive crossmatch (CM) on donor B lymphocytes. In all cases, a negative reaction was required on donor T lymphocytes using recipient pregraft sera. Sera of 36.3% and 43.6% of first and second-graft recipients, respectively, were also reactive on unseparated donor total lymphocytes. First grafts performed against donor B lymphocytes reacted like those with a negative CM in terms of graft survival, rejection incidence, and graft function in the first year. Surprisingly, an uncommonly high rate of success was observed in second grafts performed against a positive donor B-lymphocyte CM as compared to those with a negative B-cell CM (93.5% vs 62.8% graft survival at 2 years; p less than 0.05). In addition, these patients had a decreased rejection incidence and significantly better graft function (p less than 0.05) as compared to those grafted with a negative B-lymphocyte CM. In the 43.6% who also had a positive CM on total donor lymphocytes (negative CM on donor T cells) and would not have been grafted according to common CM policy, actuarial graft survival was 86.7%. Our results within the given procedure show that transplantation against a positive donor B cell CM is not detrimental to a first graft.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103155 TI - The effect of DR antigens, race, sex, and peak PRA on estimated median waiting time for a first cadaver kidney transplant. AB - 1. Fifty-six DR phenotypes account for 95% of the population waiting for a transplant and who have received a transplant. There are 15 pairs that account for 46% of the population. Large differences in the distribution of DR phenotypes between the races were observed. 2. There do not appear to be significant differences among the 15 DR phenotypes in the rate of transplantation. There are, however, significant differences in the median waiting time to a first cadaver kidney transplant across the 15 DR phenotypes. 3. Blacks are not being transplanted in proportion to their numbers on the list of those awaiting a transplant. Blacks represent approximately 27% of the population waiting for a transplant, but represent only 22.6% of the population which receives a first cadaver kidney transplant. 4. The estimated median waiting time for Blacks is almost twice that of Whites. When age, peak PRA, DR phenotype, blood type, and sex are controlled, Blacks, when compared to Whites, are still 18% less likely to receive a first cadaver kidney transplant at any point in time. PMID- 2103156 TI - The demand for transplantation in the United States. AB - Between January 1, 1980 and December 31, 1990 the number of persons awaiting a kidney transplant increased by 243%. Between December 1987 and December 1990 the number of persons awaiting a heart transplant increased by 178%, a liver transplant by 176%, a heart-lung transplant by 53%, and a pancreas transplant by 1,178%. The number of persons awaiting transplantation continues to increase, although there have been occasional monthly decreases in the number of persons awaiting a liver or a pancreas transplant. Donor supply continues to be inadequate to meet the demand for transplantation. For the past 4 years there have been approximately 4,000 donors annually. The potential supply of organ donors is estimated to be somewhere between 7,100 and 26,000 annually. However, given public attitudes toward organ donation, donor supply is probably between 5,700 and 9,300 annually. Therefore, with the exception of kidney transplantation, it is conceivable that the majority of people who are awaiting transplantation could be transplanted. PMID- 2103157 TI - The actual and potential supply of organ donors in the United States. AB - For the past 4 years (1986 to 1989), there has been virtually no change in the number of organ donors, despite significant efforts targeted toward increasing supply. The number of donors has plateaued at about 4,000 annually. Meanwhile, the number of people awaiting transplants continues to increase at a remarkable rate. Between December 1987 and December 1990, the number of people awaiting a kidney, heart, liver, heart-lung or pancreas transplant increased by 65%. This demand/supply disparity has led to much interest in the assessment of the organ procurement system. Such an assessment must endeavor to compare the supply of potential donors with actual donor procurements. Numerous studies have been conducted to estimate potential donor supply. Some relied upon the review of in hospital death records, whereas others attempted to search and identify potential donors in large mortality databases. Regardless of their source, patient records are examined and databases searched to exclude those deaths where contraindications to organ donation are present. Due to the severe shortage of donors, exclusion criteria have been relaxed to include deaths of marginal potential donors. Six major studies, all conducted between 1975 and 1991, indicate that the number of potential donors per million population is between 28.5 and 104. The most realistic estimates of supply place the number of donors between 43 and 55 per million population. The range of potential donors is, therefore, somewhere between 7,088 and 25,865. The most realistic range is between 10,694 and 13,679. These estimates must be adjusted further based upon public attitudes toward donation. Between 53% and 68% of the public is willing to donate the organs of relatives under appropriate circumstances. Thus, between 5,700 and 9,300 donors may be available annually. Whereas the demand for extrarenal organ transplantation could conceivably be met, the need for kidney donors is likely to continue to exceed supply. The situation could be improved by encouraging both living-related and living-unrelated kidney donation. Also, further consideration might be given to the possible use of nonheart-beating cadaveric donors. PMID- 2103158 TI - Organ transplantation costs, insurance coverage, and reimbursement. AB - With few exceptions, most organ transplantation procedures are expensive, although there is considerable variability in costs across transplantation programs. Because of their high cost, many public and private insurers are in the process of carefully evaluating their transplantation coverage and reimbursement policies. Some public insurers have decided to discontinue paying for some procedures on grounds that the resources expended on transplantation could be used to benefit a larger number of people without catastrophic disease. Thus, transplantation is being pitted against health promotion and disease prevention initiatives. Some insurers have also been reluctant to pay for selected transplants, arguing that they are "experimental" or "investigational." Pancreas, lung, and heart-lung transplants are often classified as such. While these decisions have a reasonable basis, concerns related purely to cost, not benefit, have made insurers hesitant to extend coverage to procedures they view as inefficacious. Transplantation programs performing pancreas, heart-lung, and lung transplantation, therefore, do so at some risk. They may not be reimbursed for the procedures they perform, or, more likely, the level of payment received is likely to be substantially below actual hospital costs. To control costs, insurers have also begun to designate transplantation centers. In doing so they limit coverage and reimbursement to programs they regard as "centers of excellence." To become a designated center, a transplantation program must meet preestablished volume and outcome requirements, which insurers believe will assure quality and minimize costs. Thus, designated centers are expected to provide cost-effective transplantation services. If insurers choose to regionalize transplantation programs, controlling both their number and distribution, it is quite possible that patient access to transplantation, as well as their choice of provider, will be severely constrained. In conclusion, concerns related to transplantation costs undoubtedly will have enormous implications for the delivery of transplantation services throughout the foreseeable future. Most significantly, the number of "qualified" centers, using insurer criteria, may be restricted to a small subset of currently active programs. This could have a dramatic affect on the start-up of new programs and the continuation of others. PMID- 2103159 TI - Update: center effects. AB - 1. From a multivariate log-linear analysis of 30,274 renal transplants between 1985 and 1989, center effects accounted for nearly 30% of all assignable variation in 1-year outcome, dominating 15 other factors analyzed. In order of accountability in 1-year graft outcome, the other important factors were donor relationship, CsA usage, donor age, graft number, highest pretransplant antibody, recipient race, HLA-A, B, and DR mismatches, cold ischemia time, donor sex, donor race, and pretransplant transfusions. Original disease, transplant year, recipient sex and age were not significant factors influencing 1-year graft survival. 2. The additive nature of these transplantation factors on the logit scale was confirmed in this analysis, implying that univariate analyses in renal transplantation are not necessarily improper. 3. There was no correlation between center effect and center size as measured by the number of renal transplants per year. Therefore, renal transplantation at small centers will not necessarily produce poorer graft function. 4. Similarly, we found only weak correlation between a center's 1-year graft survival and their patients' graft half-lives beyond 1-year. This suggests that factors determining center success in early graft survival differ from those that influence long-term success. 5. Graft survival rates among patients with and without rejection episodes prior to hospital discharge vary substantially among centers. Centers with poor 1-year graft survival demonstrated a significantly larger variation in graft survival between their patients with and without rejection than did excellent, good, and fair centers. This indicates that posttransplant patient maintenance is another factor influencing center effects on renal graft function. PMID- 2103160 TI - Long-term graft survival. AB - 1. Long-term graft survival is characterized by failure rates that are essentially constant after about a year or 2. The rate has not varied appreciably among cohorts defined in terms of transplant year. 2. Transplants with an excellent clinical course throughout the first 3 months (about 2-thirds of cadaver-donor first transplants) have substantially better long-term graft survival than those with a less favorable early course. 3. Having an excellent early clinical course did not remove the effects of the several factors related to long-term survival. 4. Use of cyclosporine did not relate to long-term survival. 5. Factors related to short-term graft survival (1 year), generally related to long-term survival and in the same direction. Cyclosporine use was a major exception. 6. The dominant factor for long-term survival was tissue matching as reflected in donor categories: HLA-identical sibling, parent, and cadaver. 7. Black recipients had a decidedly poorer long-term survival than recipients of other races/ethnicities. 8. Transplant center was a dominant factor in long-term graft survival. 9. Multivariable analysis did not materially alter the findings obtained from factors considered separately. This was attributable to the sensitivity associated with small standard errors resulting from the large number of cadaver-donor transplants and the combination of smaller numbers and longer survival of living-related transplants. PMID- 2103161 TI - The UNOS Scientific Renal Transplant Registry: multistep regression models on kidney graft survival. AB - 1. Two-step Cox regression analyses showed that, for White recipients of first cadaver transplants, pretransplant transfusions, HLA-DR mismatch, donor race, CIT, size mismatch, PRA, old donor, and recipient age were significant prognostic factors during the first 6 months posttransplant, and after that, older donor, CIT, and size mismatch continued to have effects on graft survival in the longer term. 2. For African-American recipients of first cadaver transplants, pediatric donor, cause of donor death, and increasing second warm ischemia time were major risk factors in the early period, but in the late period, the effect of donor age dominated other factors. 3. Multistep linear logistic regression and two-step Cox regression analyses yielded similar results, with donor-related and histocompatibility factors dominating survival outcome in both the short and long terms. PMID- 2103162 TI - UNOS Registry data: effect of transfusions. AB - 1. First cadaver White transplant recipients had a 4-5% increase in graft survival associated with transfusions compared with nontransfused recipients (p less than 0.001). The effect, although small, was significant, occurred at 3 months, and was evident at 1 year. This early effect (3 months) was also noted in regraft transplant recipients, living-related recipients, and 1-haplotype match transfused patients. 2. African-American and Hispanic transplant recipients did not show a transfusion effect. Indeed, African-American transplant recipients showed a reverse transfusion effect, which is in contrast to other previously reported UCLA Registry data. 3. The effect of during-transplant transfusions was negligible (ie, a 1% increase in graft survival). Additionally, one-fourth of all recipients had perioperative transfusions. 4. A transfusion effect was not shown within HLA matching for Class I antigens; similarly, little transfusion effect was found within matching groups for Class II antigens. Again, this contrasts with reported UCLA Registry data which indicated that the transfusion effect had a 10-15% difference in graft survival between the non- and transfused individuals in the 2-mismatch HLA Class II antigen group. 5. One of the most important effects on graft survival is donor age, and the preliminary data indicate that transfusions may help graft function in recipients of older donor kidneys. However, there are very few recipients in this older donor category. 6. The incidence of graft rejection was lower in transfused recipients. Additionally, graft rejection episodes remain a very potent indicator of transplant survival. That is, patients having graft rejection at 3 months showed a 20-25% lower 1-year graft survival rate than those without rejection. There were indications that there was less severe graft rejection in transfused patients; however, this could only be shown if graft rejection occurred at discharge and was not evident at 3 months or 6 months posttransplant. 7. SCr was the best indicator of 1-year graft function, even better than the presence or absence of rejection. Lower SCr levels were found in higher frequency in transfused patients. 8. There was a slight increase in graft survival associated with transfusion and PRA in first transplant recipients, and in the PRA-positive and PRA-negative groups, there was a trend toward lower graft survival for recipients with antibodies. In regrafts, transfused recipients who did not make antibodies had a 5-10% better graft survival than the nontransfused recipients without antibodies. Perhaps this indicates that transplant candidates who did not make cytotoxic antibodies after being transfused were nonresponders.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2103163 TI - Current status of allogeneic bone marrow transplantation. AB - Use of allogeneic BMTs continues to increase. During the 33-year period between 1955 and 1987, more than 20,000 patients received allogeneic BMTs; more than 50% of these were performed in the 3 years, 1985 through 1987. Transplants are effective therapy for leukemia and other hematologic diseases. They are the treatment of choice for aplastic anemia and chronic myelogenous leukemia, those who fail conventional therapy for acute leukemia, and a variety of immune deficiency disorders. Successful application of BMT is limited by complications such as graft failure, GvHD and interstitial pneumonia, and, until recently, the requirement for an HLA-identical sibling donor. In the past few years, an increasing number of transplants was performed using HLA partially matched related or unrelated donors, with some success. The development of posttransplant complications can often be predicted by risk factor assessment. In this report, current data from the IBMTR are summarized and several risk factors affecting outcome identified. PMID- 2103164 TI - Sensitization to kidney transplants. AB - 1. Greater than 50% PRA-sensitized first kidney graft recipients show significantly lower graft survival rates than nonsensitized (0-10% PRA) and moderately sensitized (11-50% PRA) recipients. Most of the effect of sensitization can be seen within the first month posttransplantation. 2. Increases in cellular immunity or antibodies not currently detected by lymphocyte cytotoxicity may account for the decreased graft survival rates in second and multiple graft recipients. One possibility involves the presence of antiplatelet antibodies. 3. Transfusions seem to be the weakest stimulus for sensitization when compared to pregnancy, and to graft failure, which is the strongest. In addition, low numbers of transfusions tend to have a beneficial effect, especially on second kidney graft survival. 4. During the years since the prospective use of the T-cell FCXM by Los Angeles transplant centers, there has been a marked increase in graft survival rates for multiple graft recipients. However, the rates for the sensitized multiple transplant group still remain lower than those for the nonsensitized first and multiple graft groups. PMID- 2103165 TI - Pediatric recipients and donors. AB - 1. Pediatric recipients comprised 6% of first cadaver transplants, 9% of cadaver retransplants, and 4% of parent donor transplants reported to the UCLA Transplant Registry between January 1984 and December 1989. 2. Very young pediatric patients (aged 1-5) had consistently poorer 1-year graft survival than older pediatric or adult recipients. Graft survival was 65%, 46%, and 86% at 1 year for first cadaver, cadaver regrafts, and first parent donor transplants, respectively. The comparable ranges for recipients over 5 years old were 73-77%, 65%, and 88%. 3. The poor outcomes for very young pediatric recipients of first cadaver transplants were mitigated by using adult male donor kidneys (75% 1-year survival) and HLA-B,DR matching (75% 1-year graft survival with 0-1 B,DR mismatch). 4. One-year graft survival improved from 66-78% with pretransplant transfusions in 11 to 18-year-old first cadaver transplant recipients (p less than 0.05), whereas transfusions improved 1-year graft survival in adult recipients by only 3%. 5. Cadaver kidneys from donors aged 1-5 yielded the lowest 1-year graft survival rate in first transplants (68%) and in regrafts (46%), whereas those from donors aged 16-18 yielded the best results (81% in first transplants and 66% in regrafts). 6. The poorest graft survival rates for each recipient age group resulted with kidneys from very young donors (aged 1-5). The lowest survival rate (51%) resulted when kidneys from donors aged 1-5 were used for recipients aged 1-5. 7. Prolonged CITs in excess of 30 hours had an extremely adverse effect on kidneys from donors aged 1-5. Kidneys from donors aged 1-5 with less than 18 hours CIT yielded 75% 1-year first transplant survival, whereas only 57% of those with more than 30 hours CIT survived. 8. The overall poorer outcome for very young pediatric recipients was apparently due to the use of age-matched donors for this group. Over 40% of first transplant recipients aged 1-5 received cadaver kidneys from donors aged 1-5. PMID- 2103166 TI - Sex and age effects in renal transplantation. AB - 1. The age and sex of the recipient were not significant factors in transplant outcome. The age and sex effects observed were all associated with the kidney donor. 2. The 1-year graft survival rates for male and female donor kidneys were 78% and 76%, respectively in first cadaver transplants and 91% and 88%, respectively, in parent donor first transplants. The donor sex had no significant effect on survival of transplants from sibling donors, irrespective of HLA match. 3. Long-term survival rates, reflected in transplant half-lives, were also significantly better in recipients of male cadaver (8 years) or paternal donor (13 years) first transplants than in recipients of female cadaver (6 years) or maternal donor (9 years) kidneys. 4. A higher percentage of HLA-A,B matched cadaver kidneys than mismatched organs were transplanted to sensitized recipients. Despite a higher percentage of sensitized female recipients, there was no difference in first cadaver transplant survival comparing males and females. 5. A positive flow cytometry crossmatch (FCXM) was associated with poor 3-month cadaver retransplant survival in both males (54%) and females (56%) compared with 83% and 76%, respectively, for FCXM-negative males and females. 6. The impact of preformed antibodies on first cadaver transplant outcome differed between males and females. Among sensitized recipients, females had 83% and 81% 3 month graft survival with a positive and negative FCXM, respectively, whereas positive FCXM male patients had 71% vs 86% for FCXM-negative males. 7. Graft survival ranged from 76%-79% in first transplant recipients aged 1-5, 6-14, 15 55, and over 55 when the cadaver donor age was 15-55. Poorer survival rates in pediatric and older recipients were associated with "age-matching" the donor kidney. Nearly 40% of pediatric patients received kidneys from pediatric donors that did poorly in all recipient age groups. More than 20% of kidneys from donors over 55 were transplanted to older recipients. These older donor kidneys also had uniformly poor survival in all recipient age groups. 8. When death was excluded as a cause of graft loss in first cadaver transplants, patients over 55 had an 80% 1-year graft survival rate. Although death was clearly a factor for older patients, it was interesting that survival including death was 76% when the donor age was 15-55 and 63% when the donor was over 55. PMID- 2103167 TI - Effect of race on kidney transplants. AB - 1. The 1-year graft survival rate for 3,525 Black recipients of first cadaver donor transplants between 1985 and 1989 was 71%. For 13,866 Whites it was significantly higher at 78%, and 796 Asians had the highest 1-year graft survival rate at 83%. 2. When transplant centers were grouped according to the number of Black patients transplanted between 1985 and 1989, 1-year graft survival rates for Blacks ranged from 67% at centers that transplanted more than 100 Blacks to 74% at centers with 50-100 Blacks to 69% at centers with 1-50 Black transplants. The corresponding survival rates for Whites were 74%, 78%, and 78%, respectively (p less than 0.01 at each center group). 3. When the results were further stratified according to donor race and age, HLA-DR mismatches, and transfusions, a significant 6% difference remained between graft survival rates of Black and White recipients (p less than 0.01). 4. Similar stratified analyses for donor race yielded a significant 8% lower survival rate for Black donor kidneys compared to White donor kidneys (p less than 0.01). 5. More than 25% of Black recipients and donor kidneys were transplanted at 6 of the 204 centers reporting to the UCLA Transplant Registry, whereas 92 centers had transplanted no Black patients. 6. The main difference in survival between Whites and Blacks was among younger patients. There was a 13% difference for those younger than 30 (p less than 0.01), and only a 4% difference among patients older than 45 (p less than 0.05). 7. When HLA-DR antigens were matched, there was no difference in the survival rate between White and Black patients. This result was unaffected by the race of the donor, implying that racial HLA-DR variants may not be a major consideration in matching. 8. Black patients had poor long-term graft survival. The kidney half-life calculated after the first year for Black recipients was 3.7 years, and was 8.7 years for Whites (p less than 0.01). 9. There was a clear "center effect" component to racial differences in first cadaver kidney transplant outcomes related to the size of the Black recipient population. These center effects did not account for the overall difference between Black and White survival rates. PMID- 2103168 TI - Outcome of kidney transplantation in different diseases. AB - A. PATIENT SURVIVAL 1. The best cadaver graft patient survival 3-years posttransplant was observed in those whose primary disease was either nephrotic syndrome (98%), renal hypoplasia (98%), renal dysplasia (98%), IgA nephropathy (96%), or medullary cystic disease (97%). The worst survival was in those with Goodpasture's syndrome (88%), hypertensive nephrosclerosis (87%), MPGN (87%), IDDM (86%), and NIDDM (85%). 2. Patient survival correlated inversely with nonimmunologic graft loss. Nonimmunologic graft loss was high in patients with hypertensive nephrosclerosis (21%), polycystic kidney disease (23%), IDDM (27%), and NIDDM (27%). 3. Females with CGN and IDDM had better patient survival than males with the same diseases. The 2-, 3-, and 5-year survivals for females with IDDM were 91%, 89%, and 87% whereas for males, they were 87%, 84%, and 81%, respectively (p = 0.01). For CGN the 2-, 3-, and 5-year survivals were 95%, 94%, and 93% for females and 93%, 91%, and 90% for males (p less than 0.01). Females with Alport's syndrome had lower patient survival rates at 1 year (86%) than males (95%, p = 0.03). B. GRAFT SURVIVAL 1. The best 3-year graft survival was in recipients whose primary pathology was IgA nephropathy with 83% for cadaver grafts and 95% for LRD grafts. This was not secondary to center effects. The worst graft survival at 3 years for cadaver kidney recipients was in those whose primary illness was NIDDM (61%), hypertensive nephrosclerosis (58%), MPGN (59%), and Goodpasture's syndrome (59%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103169 TI - Cadaver retransplants. AB - 1. Second-graft survival rates were 67% at 1 year and declined to 40% at 5 years, consistently 10% lower than those of first grafts. First- and third-graft survival rates were 77% and 58% at 1 year, respectively. The difference was apparent at 3 months. 2. Second transplants with good 1-month function had an 82% 1-year graft survival rate compared to 86% for first transplants. With good 3 month function, they had 89% 1-year survival, comparable to 91% for first transplants. 3. First-graft duration had a high prognostic value for second-graft survival. Second transplants with first-graft duration less than 3 months had 57% 1-year graft survival whereas those with more than 12 months had 75% 1-year survival. The difference was significant up to 5 years. Half-life after 1 year was 5.9 for acute responders and 5.3 for chronic responders. 4. The FCXM was a useful screening tool for second transplants. Second transplants with positive FCXM had 61% 3-month survival and those with a negative crossmatch had 82%. A positive FCXM with short first-graft duration had 48% 3-month survival and should be a contraindication for retransplantation. 5. Responder status was associated with HLA-mismatches in the first transplants. The 0-HLA-mismatched first grafts resulted in acute responders for 45-58%, which was significantly lower than 62 69% of totally HLA-mismatched first grafts. Totally HLA-mismatched first grafts were related to 3-18% lower survival for acute responders. 6. Acute responders benefited more from HLA matching than chronic responders. In acute responders, 0 HLA-A,B-mismatched grafts had a 72% 1-year graft survival rate, and 4 mis-matched had 58%. At 3 years, they had 59% and 42%, respectively. 7. HLA-DR1 recipient phenotype was associated with a 10-15% increased survival rate. DR1-positive recipients had 73% 1-year survival compared to 63% of DR1-negative recipients. 8. Never-transfused second-transplant recipients had a 59% 1-year survival rate compared to 69% for transfused. Transfusions of 1-4 units were sufficient to obtain a transfusion effect. 9. The antihuman immunoglobulin crossmatch test was associated with a 3-8% better 2-year graft survival in first and second transplants. There was no short-term beneficial effect. This assay might have detected false-negative crossmatch cases not seen by NIH or one-wash. PMID- 2103170 TI - Report on 604 six-antigen-matched transplants. AB - 1. Two-year 6-antigen-matched graft survival was 82% for first grafts and 72% for second grafts compared to 72% and 60% for the controls. 2. Six-antigen-matched transplants had longer mean ischemia times and recipients had higher levels of antibodies but the effect of these factors was insignificant compared to their effect on the controls. 3. One reason for transplant loss among the 6-antigen matched recipients was inadequate transplant size. When kidneys from young or old donors were transplanted into heavy recipients, graft survival was 74% compared to 88% for median-age donors. 4. Six-antigen-matched transplants with common phenotypes (greater than 4 cases) had 2-year graft survival of 87% compared to 76% for those which occurred only once. 5. Difficulties in tissue typing certain antigens was shown to have an effect. Six-antigen-matched transplants with antigens defined by at least 80% of the tissue typing laboratories had 89% 1-year graft survival compared to 73% for those with antigens which were more difficult to define. 6. There were fewer homozygous donors and more regraft transplants than expected. PMID- 2103171 TI - HLA peptide matching. AB - With the aid of computers, the HLA molecule for 52 specificities was cut up into peptides of 2-7 amino acids in length. From all possible peptides identified, we produced an extensive table of peptides unique to each HLA specificity. The HLA types of donors and recipients of first cadaver donor transplants were then converted to their peptides and used for matching. When compared to conventional matching, tripeptide matching was more effective in identifying patients with extremely poor outcomes. The total effectiveness of peptide matching was rather modest, although it is anticipated that this new tool, together with refined knowledge of the most immunogenic peptides, will provide a more practical method of HLA matching for allotransplantation. PMID- 2103172 TI - Occurrence of cancers in immunosuppressed organ transplant recipients. AB - The findings in this study emphasize the need for lifetime follow-up of organ transplant recipients. Currently, approximately 6% of organ transplant recipients have developed neoplasms and 1% have died of their tumors. Most deaths have been from high-grade carcinomas of various organs or from NHLs. Fortunately, a high percentage of posttransplant tumors are low-grade malignancies that are readily amenable to treatment. The future holds promise. Attempts are being made to modify the present blunderbuss attack on the immune system with more specific methods of control of certain of its components. Much work is currently being done to induce states of immune unresponsiveness directed specifically, and only, at the foreign antigens of the allograft. Hopefully these efforts will eliminate the need for long-term or intense immunosuppressive therapy and the problem of posttransplant malignancies will be relegated to a footnote in the history of organ transplantation. PMID- 2103173 TI - 1990 cell typings in the International Cell Exchange. AB - 1. A yearly summary of the previous year's cells typed through the International Cell Exchange allows a participating laboratory to compare its own performance with 292 currently participating exchange laboratories, inasmuch as each laboratory receives its individual antigen report. We present an annual summary for the 1990 typings of 40 cells sent for Class I and 20 cells sent for Class II antigens. 2. The mean detection percentages and the detection ranges for 21 WHO designated (well-defined) and 21 WHO-provisional (with "w" designations, less well-defined) antigens were determined for the Class I cells typed in 1990. Seventeen WHO antigens showed 95% or greater detection levels. The remaining WHO antigens showed at least 90% agreement, with the exception of B38. More variation in detection is observed in the WHO-provisional antigens. Aw33, Bw50, Bw60, and Bw62 showed 90% or greater average detection percents. In recent years, antigens such as Bw46 and Bw70, have shown great improvement in detection. 3. The percent discrepancy rates of 8 HLA-A,B antigens typed 4 times or more in 1990 were presented as well as the total percent discrepancy rates for all Class I antigens. Comparison of 1990 figures with those of 1988 and 1989 shows a marked decrease in the total discrepancy rates. 4. The number of false negatives and false positives for the Class I antigens indicates that few laboratories have trouble typing the WHO antigens; as many as 115 laboratories had 0 misses. However, a greater number of laboratories missed the less well-defined WHO provisional antigens: 7 laboratories had 0 misses for all the antigens and 4 laboratories had perfect records (0 false negatives and false positives) for cells typed in 1990. 5. In 1990, the cell exchange continued to study new cell variants. An A10 (A26x34) variant was detected in 4 cells and another possible variant, B7x40 (DT), was determined in 3 cells. 6. The average detection percentages and detection ranges were determined for 23 Class II antigens. Improved detection is indicated. At least 9 Class II antigens showed 90% or greater agreement level, of which at least 4 had 95% or greater mean detection. 7. Since the incorporation of DNA typing results in the B-cell line exchange reports in July 1990, the Class II antigen splits in 11 cells have been confirmed or clarified. Two Class II variants were also confirmed by the DNA laboratories. Presently, 145 serology and 7 DNA laboratories are in this exchange.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2103175 TI - Worldwide Transplant Center Directory. Kidney transplants. PMID- 2103174 TI - Early rejection: analyses of the UNOS Scientific Renal Transplant Registry. AB - 1. Rejection was the major cause of first cadaver transplant failure, accounting for 62% of failures in the first 3 years of data in the UNOS Scientific Renal Transplant Registry. 2. During the transplant hospitalization, 27% of recipients experienced 1 or more rejection episodes. The 1-year graft survival rate for patients with rejection was 65%, whereas for those who were rejection free at discharge, survival was 85%. Patients who remained rejection free through the first 6 months had a 1-year graft survival rate of 95%. 3. The incidence of early rejection decreased as the recipient's age increased. Only 18% of patients over 60 had rejection prior to their hospital discharge, and 33% of patients under 15 had early rejections. 4. The incidence of rejection was 20% for Hispanics, 27% for Whites, and 30% for Blacks. Despite the significant difference in early rejection between White and Hispanic recipients, there was no difference in the 1 year graft survival rate comparing these racial groups. Blacks had significantly poorer survival whether or not rejection occurred early than White or Hispanic recipients. 5. Sensitization had no apparent effect on the likelihood of early rejections for first transplant recipients, but graft survival was 54% for sensitized patients with rejection and 64% for nonsensitized rejection patients. 6. Prophylactic antilymphocyte antibody (ALG or OKT3) reduced rejections during the transplant hospitalization from 30% to 20%. Patients given ALG or OKT3 prophylaxis had a significantly higher incidence of rejection between discharge and 6 months than those who did not receive either treatment. There was no significant improvement in 1-year graft survival for patients treated with antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103176 TI - Analysis of the "NIMA effect" in renal transplantation. Collaborative Transplant Study. AB - In an analysis of 5,000 parent-to-child kidney transplants performed from 1983 to 1989, we found no evidence that maternal donor grafts had a better outcome than grafts from paternal donors. We conclude that a "NIMA effect" does not exist in renal transplantation. PMID- 2103178 TI - Worldwide Transplant Center Directory. Heart transplants. PMID- 2103177 TI - Worldwide Transplant Center Directory. Bone marrow transplants. PMID- 2103179 TI - Worldwide Transplant Center Directory. Heart-lung transplants. PMID- 2103180 TI - Renal transplantation in highly sensitized patients: five years of the SOS Scheme. AB - 1. One-year graft survival of 218 patients transplanted through the SOS Scheme for highly sensitized recipients was 65%. There was significant improvement in the graft survival of 135 patients transplanted from 1986 to 1988, compared to the 83 patients transplanted from 1984 to 1985 (70% vs 56% at 1 year). 2. Of the 513 patients entered into the SOS Scheme, 218 (42%) received a graft, and of those 218, 179 were transplanted within 1 year. 3. Sex and previous graft history influenced the patient's sensitization status. Males with previously failed grafts and females waiting for their first transplant appeared at greater risk of becoming highly sensitized. 4. HLA matching improved graft survival in highly sensitized patients. The effect of matching was most evident for DR and for HLA-B and DR combined. The effect of matching for HLA-A was minimal. 5. HLA-DR1 positive individuals appeared to be at lower risk of becoming highly sensitized. In addition, DR1-positive highly sensitized patients had superior graft survival compared to DR1 negative recipients. PMID- 2103181 TI - Worldwide Transplant Center Directory. Lung transplants. PMID- 2103182 TI - Worldwide Transplant Center Directory. Liver transplants. PMID- 2103183 TI - Worldwide Transplant Center Directory. Pancreas transplants. PMID- 2103184 TI - Worldwide Transplant Center Directory. Islet transplants. PMID- 2103185 TI - Worldwide Transplant Center Directory. Small bowel transplants. PMID- 2103186 TI - Worldwide Transplant Center Directory. Multi transplants. PMID- 2103187 TI - Recent trends in cadaveric renal transplantation. AB - 1. Cadaveric transplantation increased steadily from 1981 through 1986 and then leveled off. The gap between patients awaiting transplant and cadaveric transplants performed increased rapidly after 1986. 2. There has been a trend in the age distribution of cadaveric transplant recipients toward transplantation of older patients. The number of cadaveric transplants to patients 50 and over continued to increase after 1986, while the number to patients under 50 declined. The proportion of transplants to patients 60 and over has shown a particularly dramatic increase. 3. The rate of transplantation is highest in the pediatric age group and declines with age. The rate of transplantation increased in all age groups until 1986 and then declined in all age groups except the 50 and over group. The magnitude of the decline is greatest in the younger age groups. 4. Among all dialysis patients, males have a higher rate of transplantation than females, and Whites have a higher rate than Blacks. These differences in rates increase with increasing recipient age. There are moderate trends toward decreased differences by sex and increased differences by race. 5. Repeat transplants make up about 15% of all cadaveric transplants in 1988, with higher proportions of repeat transplants in the younger age groups. The transplantation rates for repeat transplants has been declining relative to that for first transplants when the relevant pool of dialysis patients is used. For the 50 and over age group, the repeat transplant rate was 3.6 times as high as the first transplant rate in 1988. 6. Compared to the general population, cadaver transplant donors are younger, less often female, and less often Black. There has been a trend toward older donors and toward a smaller difference by sex. 7. There has been a trend toward fewer nephrectomies and splenectomies prior to transplantation. 8. There are no clear time trends in sharing of organs among transplant centers and only a slight increase in the proportion of transplants with 0 HLA-antigen mismatches. PMID- 2103188 TI - Heart and heart-lung transplantation at the Johns Hopkins Hospital. AB - Since 1983, 120 patients have undergone heart transplantation and 18 patients have had heart-lung transplants at our institution. Transplantation is limited only by donor referrals but relaxation of donor criteria has increased donor availability. Immunosuppression currently consists of a 3-drug protocol of CsA, Aza, and P. Our current 1- and 5-year survival rates for heart transplants are 85% and 66%, respectively. The 1-year survival for heart-lung transplantation is 53%. Research continues in many areas of transplantation. The development of coronary artery disease in grafted hearts remains a problem. We have found that older donor age and Cmv infection are significant predictors of developing coronary disease. Routine successful extended heart-lung preservation has been difficult to achieve. A successful technique of prolonged preservation would allow for better matching, reduced logistics, and, potentially, increased numbers of donor organs. PMID- 2103189 TI - Heart transplantation: current status. AB - Two hundred ninety-three patients transplanted between March 1979 and October 1990 are reviewed. A comparison of survival curves suggests that our current triple therapy results in a half-life (15 years) which is twice that anticipated with either conventional or CsA and P therapy. Rejection occurs primarily in the first 1-3 months after transplantation and with our current therapy, is rarely seen thereafter. Infection, however, continues to be a threat with an incidence of approximately 10% per year. The major threats to long-term survival appear to be graft arteriosclerosis, infection, and malignancy. PMID- 2103190 TI - [Pneumocystis carinii pneumonia]. PMID- 2103191 TI - [Tuberculosis at an internal medicine service of a regional hospital]. AB - The causes of the maintained endemia of tuberculosis in the area of the "Hospital Arnau de Vilanova", Valencia, were studied in 162 cases treated over a 6 year period. The social conditions of the area, predisposition factors and the rare clinical and radiological first manifestations are factors influencing the maintained endemia. The introduction of invasive diagnosis techniques to confirm the disease, brought about the diagnoses of cases that with the standard techniques would have been impossible, giving the false impression of a higher incidence. We concluded that it is necessary to keep the disease in mind in the differential diagnosis of risk groups, maintaining the required epidemiological measures. PMID- 2103192 TI - [Pseudotumoral bronchial tuberculosis]. AB - We analyse our own experience of a rare tuberculosis presentation that we call pseudotumoral bronchial tuberculosis. 9 cases were studied, which due to radiological, endoscopic and clinical features, a diagnosis of bronchogenic carcinoma was made. The median age was 63.7 years, 7 were male and 2 were female. The hilar or mediastinic radiological pattern was frequent. The bacterial diagnosis was made through the study of the samples obtained by bronchoscopy, except in 2 cases which were diagnosed through post-bronchoscopy sputum examination. The bronchial biopsy showed the typical necrotic granulomas of tuberculosis in only one case. Supported by the bad evolution of our patients treated without steroids, the possible efficacy of early use of steroid is suggested to avoid the most important sequelae, bronchial stenosis. PMID- 2103193 TI - [Changes in exercise capacity and in induced ischemia with an oral dose of 5 isosorbide mononitrate in patients with stable angina pectoris]. AB - In order to establish the effects of 5-isosorbide mononitrate on: the exercise capacity, the onset period of angina and ischemia along with the degree and on whether the duration time was prolonged up to 5 hours after the oral administration of 20 mg of this drug, we compare this drug against a placebo in a group of 15 patients with stable angina pectoris developed by effort who performed an exercise test using a bicycle ergometer. After the administration of 20 mg of 5-isosorbide mononitrate it was observed that onset time of angina (p less than 0.001), the onset time of ST decrease (p less than 0.002) and total time of exercise attained were significantly superior to those found in patients with placebo administration. Moreover, for the same degree of EKG ischemia (ST decrease) showed a superior exercise time was registered (p less than 0.002) after the administration of 5-isosorbide mononitrate (5-IM). Our results show that an oral dosage of 20 mg of 5-IM given to patients with stable angina pectoris increased the capacity and exercise tolerance delaying significantly the onset time of angina, the onset time of EKG ischemia and its decree induced by the effort up to 5 hours after its administration. PMID- 2103194 TI - [Sepsis at an internal medicine department]. AB - 185 cases of bacteremia admitted at the internal medicine department of "C.S. Virgen de la Arrixaga" in Murcia from 1977 to 1986, were studied retrospectively. The common infection was significantly associated to Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus A group and Neisseria meningitidis and the nosocomial infection was associated to Klebsiella Pneumoniae, Serratia Marcescens y Pseudomonas aeruginosa, Staphylococcus epidermidis and Enterobacter. We did not find significant differences between the common and nosocomial infection caused by E. Coli and Proteus mirabilis. These factors were associated to an increase of mortality: age greater than 40 years, nosocomial infection, Pseudomonas aeruginosa, other associated rapidly lethal diseases, acute clinical state at the beginning of bacteremia, shock and non-correct antibiotic therapy. PMID- 2103195 TI - [Convulsions and encephalopathy as initial manifestations of cyanocobalamin deficiency, without hematologic changes]. AB - A case of deficiency of cobalamin coenzyme synthesis whose first manifestation was encephalopathy with seizures and no trace of megaloblastic anemia is presented. After a while, signs of posterior cord and polyneural disfunction were detected. We highlight the rareness of the case and the difficulty of the diagnosis because of the discrepancy between neurologic and hematologic signs, as well as the need for early diagnosis which is an important factor for observing therapeutic response. PMID- 2103196 TI - [Sweet's syndrome]. AB - A 42 year old female, diagnosed as having Sweet's syndrome, is presented as a new case of this rare disease (less than 100 cases reported before 1985) and the literature of the syndrome is reviewed. The clinical and histological features and its association with other diseases, especially the pathogenesis and treatment, are commented on. PMID- 2103197 TI - [Prolonged course fever as presentation form of Crohn's disease]. AB - 3 cases of Crohn's disease whose first manifestation was fever preceding intestinal symptoms, 3, 12, and 36 months respectively, the intestinal symptoms, are presented. Apart from fever, one of our cases had multiple extraintestinal symptoms these being of pancreatic, hepatic, mucocutaneous, bone and ocular origin. We insist on the heterogeneous onset of the disease which forced the clinician to maintain this disease on the long list of prolonged febrile illnesses causes. PMID- 2103198 TI - [Amiodarone: new concepts on its anti-arrhythmic effect]. PMID- 2103200 TI - [Tolosa-Hunt syndrome: a case report]. PMID- 2103199 TI - [Miliary tuberculosis in adults. Study of 67 patients]. AB - 67 patients with miliary TB diagnosed over a 15 year period (1973-1987) have been retrospectively studied. The clinical and analysis data were evaluated, highlighting different factors associated to higher mortality. 53 patients diagnoses were made premortem and 14 had the diagnosis made post-mortem. The age of the patients was of 48 +/- 21 (mean +/- DE) years, inferior to other series, this showing a higher prevalence and early age of infection in the area. 63% had miliary radiological features; the most frequent tests performed were liver biopsy with profitability of 80% and bronchoscopy which, together with transbronchial biopsy and bacterial analysis of the bronchoalveolar lavage, showed a positive diagnosis of 60%. The factors which were associated with bad prognosis were cavitated or chronic lesions (P less than 0.01), chronic diseases and immunosuppression factors associated, this not being statistically significant. PMID- 2103201 TI - [Skin involvement in Hodgkin's disease]. PMID- 2103202 TI - [Simultaneous Legionella pneumophila and Coxiella burnetti infections]. PMID- 2103204 TI - [Nocardiosis in a patient who has undergone renal transplantation]. PMID- 2103203 TI - [Panic attack secondary to the oral administration of a sustained-release preparation of theophylline]. PMID- 2103205 TI - [Metabolic coma caused by alcoholic ketoacidosis]. PMID- 2103206 TI - [The pulmonary hypertension of portal hypertension]. PMID- 2103207 TI - [Dyslipemia in physicians. The need for a plan of primary prevention of atherosclerosis in our country]. AB - A comparative study of the total cholesterol (TC) and its fractions was carried out in 3 groups of males. The first group consisted of (C) 53 healthy males (18 between 30-39 years old, 17 between 40-49 and 18 between 50-65); the second group (M) was of 57 male doctors (19 between 30-39 years old, 21 between 40-49, and 17 between 50-65); third group (E) was of 94 males with myocardial infarction (22 between 30-39 years old, 32 between 40-49, and 40 between 50-65). TC was significantly lower (p less than 0.02 and p less than 0.001) in both the lower ages ranges in Group E compared to Groups C and M in all age ranges. Group M showed significantly lower (p less than 0.001) in Group E compared to Groups C and M in all age ranges. Group M showed significantly lower HDL-C (p less than 0.01) and to group M in the lowest age range (p less than 0.005). LDL-C was significantly higher (p less than 0.001) in Group M compared to C in the higher age range. VLDL-C was higher (p less than 0.05) in Group E compared to C in both the higher age ranges (p less than 0.05) as well as to the middle age range of Group M (p less than 0.05). The indexes TC/HDL-C and LDL-C/HDL-C were significantly higher in Group E compared to Groups C and M in all age ranges. These indexes were significantly higher (p less than 0.01 and p less than 0.05) in Group M compared to group C in all age ranges.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103208 TI - [The identification of plasma calcitonin in liver cirrhosis]. AB - Increased levels of plasmatic calcitonin (PC) have been found in patients afflicted with liver cirrhosis (LC). Different circulating polypeptides of calcitonin with contrasting molecular weight (MW) have been observed by way of several methods of identification. The aim of our study is identify these types of PC in patients afflicted with LC, using a gel chromatography technique, comparing them with those obtained from patients with thyroid medullar carcinoma (TMC). A first PC peak with MW of 30,000 daltons (D) corresponding to macromolecular types of PC of LC was observed. Furthermore, a second peak of PC, corresponding to a synthetic human calcitonin and to monomers of PC in patients with TMC was noted. This indicates is a slight increase of monomeric PC in patients with LC, although its biological function is unknown. PMID- 2103209 TI - [The prevalence of arrhythmias and repolarization changes in patients with mild or moderate essential hypertension undergoing an exercise test. Their variations with different antihypertensive treatments]. AB - 42 mild and moderate hypertensive patients treated with Verapamil, Atenolol and Xipamide were studied. Exercise tests (ET) were performed at the onset and after a month of therapy, in order to detect arrhythmias and repolarization change prevalence of ventricular arrhythmias (VA) was 23.7% and 11.9% for supraventricular arrhythmias (SVA). 45.2% of the exercise tests were considered positive, with a significant correlation with maximum pressure peak. Patients with left ventricular hypertrophy (LVH) showed a significant increase in VA and +ET prevalence (42.1% and 63.2%). After treatment, the prevalence for VA registered a slight decrease and an increase for SVA; these differences not being considered significant. +ET showed a significant decrease in all patients, as well as in those with previous LVH (21.4%, 26.3%). Only atenolol produced a significant decrease in the +ET of patients with previous LVH (75% to 12.5%). PMID- 2103210 TI - [The usefulness of the Peak Flow Meter for assessing patients with acute respiratory disease]. AB - The aim of the study was to evaluate the utility of the extrahospital use of "Peak Flow Meter" (PFM) in patients with an acute respiratory disease. 70 patients were studied. PFM, arterial gasometry, physical examination and dyspnea evaluation were performed on all of them. The PFM were posteriorly transformed into the rate related to the ideal result, following the Nunn and Gregg equation (1989). We found an association between the PFM rate and the different arterial blood gas test results, and a relation to the degree of dyspnea and the listening of sibilant rales. There was more significance with the rate of PFM than with the PFM transformed in all cases, and only association was found between arterial blood changes and PFM. We concluded that all patients with an acute respiratory disease with a rate of PFM greater than 50% should be evaluated carefully because of the probability of existing hypoxemia, and those with rate of less than 20% must be referred to hospital. PMID- 2103211 TI - [Posttreatment hypothyroidism in diffuse toxic goiter. A complication or evolution?]. AB - Hypothyroidism posttreatment of diffuse toxic goiter (DTG) might depend on both treatment of inherent disease factors. 147 patients afflicted with DTG, with at least 3 years under treatment, were studied to identify these factors. Clinical evaluation was performed and TSH and T4T were measured (RIA). 49% had hypothyroidism, 17% of this percentage having been diagnosed during the study. We found these hypothyroidism protector factors: familiar background of thyroid disease, gap between doses of 131 1 greater than of 8 months and as favoring factor: surgical treatment. PMID- 2103212 TI - [Conservative treatment in spontaneous splenic rupture due to infectious mononucleosis]. AB - Spontaneous rupture of the spleen secondary to infectious mononucleosis frequently proves to be an urgent surgical decision: splenectomy during a exploratory laparotomy. Few cases have been described where diagnosis was made by means of an abdominal ultrasound and those followed-up and treated conservatively, are most exceptional. A case of rupture of spleen during a course of an infectious mononucleosis, confirmed by abdominal ultrasounds and treated conservatively, with good evolution, is presented. PMID- 2103213 TI - [Acute pleuropericarditis and cardiac tamponade as extraintestinal complications of ulcerative colitis]. AB - Pericarditis and cardiac tamponade are very rare complications of inflammatory disease of the bowel. A case of a patient with ulcerative colitis, who subsequently developed pericarditis, cardiac tamponade and pleural effusion during a latent phase of the baseline disease, is presented. At the same time, the papers published on this subject are reviewed. The presence of dyspnea, tachypnea, of pleuritic pain in patients with ulcerative colitis must be taken into consideration, and all the tests necessary to study a pleuropericardial pathology should be performed. PMID- 2103214 TI - [Progressive external ophthalmoplegia]. AB - Progressive external ophthalmoplegia is a myopathic alteration of slow progression which affects the extrinsic ocular muscles; ptosis of the eyelid being the most characteristic sign. Nowadays, it is included as type of muscular dystrophy. Even though mitochondrial changes have been described, they are not specific to this disease. 2 cases are described in this paper, commenting on clinical, electromyographic and pathological aspects. PMID- 2103215 TI - [HIV and schizophrenia]. AB - We report five cases of psychosis in patients with antibody to human immunodeficiency virus. All patients was man and intravenous drug abuser. The age range was 22 from 31 years with a mean of 25 years. In all cases acute schizophrenia was the first clinical picture of the HIV. Four patients had opportunistic infections and AIDS-Dementia Complex months later. If there is a genuine biological association between HIV carriage and schizophrenia illness, then HIV infection should be considered in the differential diagnosis of such an illness. PMID- 2103216 TI - [Drug surveillance for adverse reactions in patients with human immunodeficiency virus infection]. AB - Human immunodeficiency virus (HIV) carrier patients experience several secondary effects with drugs, being mainly skin reactions and myelosuppression. Owing to this, close observation of patients is necessary with regard to therapeutic and prophylactic schedules. In this paper, we describe the secondary effects of zidovudine in 60 patients of groups III and IV from CDC. The main toxicity was found in bone marrow; with anemia in 50% and leukopenia in 53% of patients. Finally, the more frequent secondary effects of therapy for opportunist infections are analysed. A guide for identifying the drugs' secondary effects is also included, based on our experience and on a wide range of literature reviews. PMID- 2103217 TI - [Erythema nodosum associated with chronic lymphatic leukemia]. PMID- 2103218 TI - [Recurrent macroscopic hematuria as the first manifestation of Rendu-Osler disease]. PMID- 2103219 TI - [Hepatic abscess: its diagnosis and treatment]. PMID- 2103220 TI - [Bilateral pulmonary nodules in Hodgkin's lymphoma]. PMID- 2103221 TI - [Nasal tuberculosis: a rare entity]. PMID- 2103222 TI - [Acute abdominal pain due to food lead poisoning]. PMID- 2103223 TI - [Paroxysmal auricular fibrillation after acute alcohol ingestion]. PMID- 2103224 TI - [Early amyloidosis in Crohn's disease]. PMID- 2103225 TI - [Refractory hypercalcemia as the first manifestation of esophageal cancer]. PMID- 2103226 TI - [Multifactorial classification of vasculitis. A critical review]. AB - The present classification of vasculitis has several objections, based on the following aspects: 1) It does not take into account taxonomic rules; 2) It uses criteria which helps to cover up; 3) It uses generic terms without a specific meaning; 4) Lack of clinical interest. We comment on the best known classifications focusing on the main objections. We propose a multifactorial classification based on Klemperer, Pollak and Baehr studies. PMID- 2103227 TI - [Rapidly progressive cardiac insufficiency as presentation form of auricular myxoma]. PMID- 2103228 TI - [Mycobacterium avium-intracellulare infection of the skin in a patient with AIDS]. PMID- 2103229 TI - [Paralysis of the sixth cranial nerve and headache after dural puncture]. PMID- 2103230 TI - [Klinefelter's syndrome. 48 XXYY]. PMID- 2103231 TI - [Marfan's syndrome and rheumatoid arthritis]. PMID- 2103232 TI - [Cushing's syndrome secondary to adrenal gland carcinoma controlled with ketoconazole]. PMID- 2103234 TI - [Biliary lithiasis: non-surgical therapeutic options]. PMID- 2103233 TI - [Primary pyomyositis simulating malignant tumor]. PMID- 2103235 TI - [Intestinal calcium and vitamin D absorption in essential arterial hypertension]. AB - The intestinal absorption of calcium and seric levels of calcifediol and calcitriol were studied in 27 patients with essential blood hypertension (BH) and 20 normal patients in a control group. The hypertensive patients were divided in three groups depending on the plasmatic renin activity (PRA), (high, normal, low). We found a significantly higher rate of intestinal calcium absorption in the group of patients with BH and low PRA than in the control group (22.73 +/- 19.05 and 10.7 +/- 17.13% respectively) (p less than 0.025). The seric levels of calcitriol (1,25 (OH) 2D3) were significantly higher in the group of patients with hypertension and low PRA than in the control group (48.16 +/- 5.25 and 33.13 +/- 2.9 pg/ml respectively) (p less than 0.025). The seric levels of calcifediol (25-OH-D3) were significantly lower in low PRA patients than those patients in the control group (12.37 +/- 2.44 and 21.94 +/- 2.82 ng/ml respectively) (p less than 0.025). We concluded that patients with essential blood hypertension and low PRA have significantly lower calcitriol levels than any other group, probably conditioning the greater intestinal calcium absorption shown in this group. PMID- 2103236 TI - [Changes in phagocytosis of aerobic bacteria by neutrophils after exposure to subinhibitory concentrations of aztreonam and ciprofloxacin]. AB - In the present research work we are performing a study on the effect of the antibiotic concentrations low minimal inhibitory concentration of aztreonam and ciprofloxacin on phagocytosis of aerobic bacteria by neutrophils (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa). Both antibiotics induced an increased of phagocytosis by similar mechanisms. In our assay aztreonam and ciprofloxacin would not act directly on granulocyte but they would affect the bacteria increasing the opsonization and phagocytosis. PMID- 2103237 TI - [Neurologic manifestations of polycythemia vera. Analysis of 24 cases and review of the literature]. AB - Neurological symptoms (NS) of 33 patients diagnosed as suffering from polycythemia vera (PV) are described. 24 of them (73%) had NS at some point in their evolution, the most frequent being related to blood hyperviscosity (headache 51%, dizziness 36%, paresthesias 30%, sight alterations 21%). 5 patients had ictus (15%) and there were no bleeding symptoms in the nervous system. There were no significant differences (p greater than 0.05) in age, sex; hematocrit, platelet or volume of packed red cells, between patients with NS and those without NS. A complete remission of NS was obtained reducing the hematocrit, except in ictus patients. We did not find mortality, as a result of NS. PMID- 2103238 TI - [Decompensated diabetes mellitus and circadian rhythm of plasma TSH]. AB - The plasmatic levels of TSH in 2 group of diabetic patients (7 decompensated and 8 decompensated, but in treatment) were measured at 9:30 and 23:30 hours. The mean glycemia levels were of 280 +/- 45 and 150 +/- 30 mg/dl (p less than 0.0005). There was no significant difference between daily TSH and nocturnal TSH in any of the groups, but there was a tendency for the nocturnal TSH to be higher in decompensated patients. There was no difference when comparing the TSH of the first group to the TSH of the 2nd group. The mean TSH N/TSH D was superior by 1 (1.36 in decompensated and 1,095 in treated patients). The correlation between glycemia and TSH D was negligible in all groups. The data suggests the tendency that the circadian rhythm of TSH in maintained in diabetes decompensation with shorter rhythm registered in treated patients. This shows a certain normality in the suprahypophysary area in charge of the rhythm and is similar to the minor liberation of TSH after TRH stimulus that other authors have described as happening in the decompensation of diabetes mellitus. PMID- 2103239 TI - [Cardiac tamponade as presentation form of lymphoma. Presentation of a case and review of the literature]. AB - A case of non-Hodgkin's lymphoma, centrocitic and centroblastic which was presented as cardiac tamponade, is described. The literature is reviewed commenting on other 14 cases with the same presentation. In spite of the rareness, we highlight the importance of its early diagnosis to prevent the hemodynamic alterations, this being after its control with the same prognosis of other patients afflicted by lymphoma. PMID- 2103240 TI - [Pachydermoperiostosis (primary hypertrophic osteoarthropathy)]. AB - A case of pachydermaperiostosis in a 16 year old male is presented. The main clinical features were bilateral mechanical gonalgia, acropachy, bilateral palpebral ptosis and hyperhydrosis. The diagnosis was confirmed by X-ray, showing a wide, symmetric periostosis. The literature is reviewed and the differential diagnosis is commented on. PMID- 2103241 TI - [Mycosis fungoides associated with HIV infection]. AB - The increasing number of cases of HIV-infections made the pathology association wider. Between these pathologies, tumors and lymphoid neoplasias are the most frequent. Large series showed the association between B-cell non-hodgkin lymphomas, and HIV infection, but only exceptional cases of T-cell lymphomas were found. We present a case of T-cell cutaneous lymphoma (mycosis fungoides) in a patient with HIV-infection owing to the fact that very few: cases have been reported, the causal relationship is still unknown. PMID- 2103242 TI - [Spontaneous pneumothorax in pregnancy: description of a case and review of the literature]. AB - A case of pneumothorax during the 8th week of pregnancy is described. The literature is reviewed. We highlight the rareness of the case and discuss of possible relationship with protector hormonal factors. PMID- 2103243 TI - [Biliary lithiasis: non-surgical therapeutic options]. PMID- 2103244 TI - [Syringomyelic arthropathy]. AB - 8 cases of syringomyelic arthropathy which were detected in 6 patients of 13 afflicted of syringomyelia, are presented. The etiopathogenesis, clinical, radiological, and pathological data are commented on; and an eclectic mechanism which mixed the 3 theories admitted: neurotrophic, neurotraumatic, and neurovascular, is suggested. We found the incidence of arthropathy higher than that described in existing medical literature and concluded that it is necessary to perform wide administer the appropriate therapy. PMID- 2103245 TI - [The electrocardiographic changes in constrictive pericarditis before and after pericardiectomy. The role of the myocardium in the genesis of preoperative electrocardiographic changes]. AB - We studied 19 patients diagnosed of chronic pericarditis and treated surgically with pericardiectomy, to evaluate the role of the pericardium and myocardium on the preoperative electrocardiogram. Before surgery, there was atrial fibrillation in 17 cases, the P axis was between 0 and +70 and pseudomitral morphology was found in 10 of the 12 cases with normal sinus rhythm. The mean voltage in the QRS complex was (13.8 mm), and the R wave in V5 8.6 mm. The T wave was negative in 17 patients. After surgery there was only a case of atrial fibrillation that converted to normal sinus rhythm; the P wave axis moved to the right between +30 and +150 (p less than 0.002), the pseudomitral morphology of the P changed to normal in 3 cases, the voltage of the QRS increased to 16.7 mm (p less than 0.003) and that of the R wave in V5 to 9.4 mm (p less than 0.001). The T wave became positive in only 3 cases. Because of the persistence of some alterations, we concluded that both components, pericardium and myocardium are important in the changes of the electrocardiogram of constrictive pericarditis. PMID- 2103246 TI - [HTLV-I infection in a high-risk group]. AB - The aim of this study is to detect the presence of HTLV-1 in a high-risk population in west Andalusia. We studied 267 samples of serum from 255 patients: 179 of these patients being intravenous drug-users, 14 had ADVP sexual partners, 16 were inhalation drug-users, 4 were hemophiliacs, 9 had other high-risk habits and 25 hematological patients afflicted with leukemia or lymphoma. All of them were tested for antibodies against HTLV-1 by means of an in vitro qualitative ELISA technique (ELISA Du Pont HTLV-1). The positive results were confirmed by the Western blot technique. Additionally, the p24 antigen and the antibodies against VIH-1 and VIH-2 (ENV/CORE) were analysed, except in the 25 hematological patients. We found 20 serum samples positive to HTLV-1 by ELISA (7.4%), but only 1 (0.3%) was confirmed by the Western blot technique. The prevalence of VIH-1 was 46%; 9% had p24 VIH antigen and 26% had false positive ELISA to VIH-2. We found a statistically significant relationship (p = 0.0005) between positive ELISA to HTLV-1 and antibodies against VIH. We conclude that HTLV-1 has penetrated into the high-risk population of west Andalusia , although not yet to a great degree, and point out the need for seric epidemiological surveillance to prevent the spread of the retrovirus in these groups. PMID- 2103247 TI - [The multiple-admissions patient in internal medicine as a special type of hospital readmission]. AB - A considerable number of patients treated in hospitals register several readmissions, this being special cause for concern, not only from a clinical point of view but also in respect of the management of resources. This article analysed the clinical, epidemiological and resources variable associated with patients classified as "multiadmitted". The aim of the study is determine the possible factors which predispose the multiadmission. Multiadmitted patients are defined as those who are admitted twice in a period of 12 months or those admitted 3 times in 5 years. The type of the study carried out involved control cases. We selected 1099 admissions during a period of a year at an internal medicine department of a third-level hospital. Among the various results, we would highlight the fact that 34% of the patients were multiadmitted. The main characteristics were: mean age of 8 years older than the others, patients afflicted with chronic diseases of high prevalence (most of them of the respiratory, cardiovascular, gastrointestinal or endocrine systems). The most frequent diseases were COLD (Chronic Obstructive Lung Disease), cardiomyopathies, and chronic liver disease). PMID- 2103248 TI - [Intracranial hypertension and subarachnoid hemorrhage: the forms of presentation of neurobrucellosis]. AB - 2 exceptional cases of neurobrucellosis, which manifested as intracranial hypertension and subdural hemorrhage, are presented. A revision of the subject was carried out. We consider that the association of two antibiotics (rifampin, doxycycline or trimethoprim/sulfamethoxazole) are valid and should be administered until the symptoms disappear and the CSF becomes normal. We suggest that all nervous system symptoms in our area, which are not clear, should be studied for brucella because sometimes these are the only features of neurobrucellosis. PMID- 2103249 TI - [Primary mesenteric venous thrombosis]. AB - Mesenteric venous thrombosis is a rare disease, and is secondary to several known causes. Recently, it has been proven that some coagulation alterations (such as: antithrombin III deficit, plasminogen, S protein, etc.) play a role in its pathogenesis. Nevertheless, 10% of the cases are still of unknown origin (primary mesenteric venous thrombosis). We present a case of primary mesenteric venous thrombosis with a very good clinical evolution. PMID- 2103250 TI - [Sweet's syndrome. Its association with chronic inflammatory bowel disease]. AB - Sweet's syndrome, or febrile neutrophilic dermatosis, is a disease first described by Sweet R.D. in 1964 as a dermatologic disease. Subsequently, it has been associated to several disease. One of those rarely describe is the association to chronic intestinal inflammatory disease. We reviewed the cases studied in our hospital since 1980 and found two cases associated to chronic intestinal inflammatory disease. We recommend the carrying out of gastrointestinal studies in patients afflicted by Sweet's syndrome to detect its association. PMID- 2103251 TI - [Diffuse melanosis in metastatic malignant melanoma with melanuria]. AB - We report an additional case of diffuse melanosis secondary to metastases from malignant melanoma in a patient, who was seen in our department shortly before death. We couldn't localize the origin of the primary neoplasm. After reporting the case, we discuss the pathogenesis of melanosis and possible sites of the primary tumor. PMID- 2103252 TI - [The current situation of therapy in hyperlipemias]. PMID- 2103253 TI - [Acute mountain sickness]. AB - Acute mountain sickness is a pathologic reaction as a result of bad adaptation to high altitudes (greater than 2.500 meters). The main symptoms are headache, nausea, vomits, and insomnia. When severe it can produce oliguria, retinal hemorrhage, ataxia and sometimes coma. Its etiology is not well known. It is considered that the first producer factor of the disease is tissular hypoxia secondary to low partial oxygen pressure existing in areas of high sea level. The treatment consists of descent and the use of dexametasone and acetazolamide. PMID- 2103254 TI - [Fever of unknown origin and CVA as the first manifestation of giant-cell arteritis; apropos a case]. PMID- 2103255 TI - [Voluntary isoniazid poisoning. Apropos a case]. PMID- 2103256 TI - [Temporal arteritis with painful swellings on the scalp]. PMID- 2103257 TI - [A generalized infection by Bacillus sp]. PMID- 2103258 TI - [Cholestasis of an infrequent etiology: Mirizzi's syndrome]. PMID- 2103259 TI - [Antiphospholipid antibodies and angor]. PMID- 2103260 TI - [Details on the anatomy of the retrocrural space]. PMID- 2103261 TI - [Multicentric giant plasma-cell lymph node hyperplasia]. PMID- 2103263 TI - [The value of microscopy in tuberculosis]. PMID- 2103262 TI - [A new case of round pneumonia]. PMID- 2103264 TI - [The clinical value of a new microscopy technic in the rapid diagnosis of pulmonary tuberculosis]. AB - 860 samples from lungs were processed in our laboratory, simultaneously using Smithwick's fluorescent technique and a fluorescent thick-drop technique, previously described by us. We found a sensitivity of 82.06% and 86.54% for Smithwick's fluorescent technique and thick drop technique, respectively. This technique is faster and more sensitive than any other currently known. PMID- 2103265 TI - [Duodenal ulcer disease. A controlled study of aggressiveness and other personality factors]. AB - We study the aggressivity level and its direction in the context of personality, in 36 patients with DUD (23 males and 13 females). We employed 30 patients with chronic disease (15 men with COPD and 15 female with arthrosis) as control groups, in addition to the normal population. The purpose of this investigation is to determinate if suffering or chronicity could determinate psychopathological findings similar to those described in the literature about patients with DUD. The results point out that we can not consider a specific ulcerous personality, but a psychophysiological reaction or psychopathological alterations resulting from a somatic disease, on the other hand the autoaggressivity factor pulsion inhibition, is the most reliable variable when compared with control groups (p less than 0.05-0.01). PMID- 2103267 TI - [An analysis of the mortality from extrapulmonary tuberculosis in the catchment areas of the community of Valencia (1976-1980)]. AB - Tuberculosis is a chronic infectious disease produced by Mycobacterium tuberculosis or Koch's bacillus, which mainly affects the airways and, less frequently, other organs in the body. Tuberculosis is still a health and social problem in Spain. The data of this study were obtained from "Monografias Sanitarias", "Analisis de Mortalidad", published by "Generalitat Valenciana", the standard mortality rate was calculated by direct methods. Mortality is not the best sanitary parameter to study the real situation of this disease, because the present methods of treatment are effective and death caused by tuberculosis is very rare. Despite the aforementioned fact, when comparing the mortality data of different health areas during a period between 1976 and 1980, we confirm that this disease persists as a cause of death in our community. PMID- 2103266 TI - [Bacteremia of cutaneous origin]. AB - 558 episodes of bacteremia were detected in our medical center during a 2-year period. 17 of them (3%) were of cutaneous origin. 12 cases were community acquired and 5 were hospital-acquired. The patients median age was of 65 years. 15 patients had a baseline disease, the most frequent being diabetes mellitus and neoplastic disease. The most common bacteria isolated were group A beta-hemolytic Streptococcus, Staphylococcus aureus, and Escherichia coli; 2 patients had multibacterial episodes. Decubitus ulcer and cellulitis were the most frequently associated skin disease. Global mortality was of 47% and was sepsis related in 29% of the cases. Death prognosis factors were old age, diabetes mellitus, gram negative causal bacteria, nonappropriate antibiotic therapy, low index of clinical suspicion. PMID- 2103268 TI - [The reactive hemophagocytic syndrome associated with infection: a study of 3 cases]. AB - Reactive hemophagocytic syndrome (RHS) or hemophagocytic histiocytosis is a disease with anatomo-pathological features of systemic proliferation of non neoplastic histiocytes, with prominent hemophagocytosis, associated to infection of other diseases. The cases of three patients afflicted with RHS are presented. 2 of them secondary to a brucellosis and the other of unknown origin. The clinical features were similar: high fever, wasting, and splenomegaly. Pancytopenia existed together with liver disfunction, CID and hyperferremia. Marrow infiltration of reactive histiocytes with important hemophagocytic phenomenon, demonstrated by aspirated and bone marrow biopsies, were observed in all cases. Studies of the immunology system were performed, showing changes in two of them. All of them fully recovered after antibiotic treatment. PMID- 2103269 TI - [The hemolytic-uremic syndrome: a report of a case which started as a massive pulmonary hemorrhage]. AB - Hemolytic-uremic syndrome is a disease of different etiology, characterized by thrombocytopenia, hemolytic anemia and renal failure. A case of lethal evolution that afflicted a 18 year old male is presented. The exceptional presentation with massive pulmonary hemorrhage highlighted. PMID- 2103270 TI - [Chylous ascites secondary to a carcinoid tumor]. AB - A 68-year-old male with abdominal swelling and wasting of one month's evolution had chylous ascites. The clinical study of the patient showed a retroperitoneal tumor and a distal jejunum and mesenterium affliction. There were metastatic nodules in peritoneum, epiploic appendix and malignant pleural effusion. The histological study showed a carcinoid tumor. Chylous ascites is an exceptional complication, and a bad prognosis factor of carcinoid tumor. PMID- 2103271 TI - [Hypertensive crises and emergencies: the concept and initial management]. AB - The high prevalence of blood hypertension together with a deficient control, make this one of the frequent causes requiring urgent medical attention. The concepts are reviewed and the treatment of the hypertensive urgency and emergency are described. The term hypertensive emergency means a serious affliction of vital organs caused by the increased of blood pressure, this needing a very close control and parenteral treatment. Hypertensive urgency is a less severe situation, which requires a less aggressive via-oral or sublingual treatment. PMID- 2103272 TI - [Ocular infections in drug addiction: the microbiological characteristics and diagnostic difficulties]. PMID- 2103273 TI - [The role of glucagon in the treatment of severe hypoglycemia]. PMID- 2103274 TI - [Pseudo-Meigs' syndrome. A case report]. PMID- 2103275 TI - [A liver abscess due to alpha-hemolytic Streptococcus associated with brucellar granulomatous hepatitis]. PMID- 2103276 TI - [Cancer of the lung as a second primary neoplasm]. PMID- 2103277 TI - [Pyogenic liver abscess: its treatment with or without drainage]. PMID- 2103278 TI - [Thyroid hemiagenesis]. PMID- 2103279 TI - [An atypical bronchial carcinoid with diffuse pulmonary involvement]. PMID- 2103280 TI - [Acute rhabdomyolysis and rough physical exercise]. PMID- 2103281 TI - [Myopathy and bicytopenia as the first manifestation of primary autoimmune hypothyroidism, apropos a case]. PMID- 2103282 TI - [Massive hemoptysis and selective intubation]. PMID- 2103283 TI - [The quantification of bone mass]. PMID- 2103284 TI - [Reiter's syndrome. A study of 25 cases]. AB - The laboratory, radiological and clinical features of 25 cases of Reiter's syndrome were studied. Most of the subjects were between the 2nd and 4th decade of life (p less than 0.05). We observed a high incidence in females: 92% (p less than 0.01) and a high rate of alcoholism: 24%. Knees (72%) and ankles (44%) were the most afflicted joints. Urethritis (87.5%) and eye problems (87.5%), predominantly conjunctivitis (76%), were the more frequent extra-articular manifestation. HLA-B27 were positive in 81.8% (18/22). Sacroiliitis was confirmed radiologically in 8 patients (32%), being asymmetric in 6 of them. "Fluffy" periostitis (20%) was the more frequent peripheral articulation. The treatment used was indomethacin; we obtained good results in 20 subjects; the remaining 5 had to be treated with steroids to control ocular and joint symptoms. Two or more episodes occurred in a low rate of patients: 28%. PMID- 2103285 TI - [The neurophysiological study of diabetic polyneuritis. Apropos 100 cases]. AB - Alterations in nervous transmission might be an early feature of diabetic peripheral polyneuropathy, even in the subclinical stage. We performed a study on 100 diabetic patients. Those with possible endogenous or exogenous causes of neuropathy were not included. We studied the motor distal latency of right peroneal and cubital nerve and the sensory distal latency of median nerve by the use of electromyogram. The neuropathy incidence was 34.3%. One of the results was that conduction in males was slower than in the female control group; this disappeared in diabetic patients. PMID- 2103286 TI - [An analysis of 14,000 patients admitted to an internal medicine service during 1982-1988]. AB - We analysed the discharge reports of patients admitted during 1982-1988 to an internal medicine department of a university hospital. There were 927 deaths among 13,913 patients (6.66%); the median age of the persons admitted was 59.50 years while the median age of the patients who died was 72.87 years. Both groups suffered from several afflictions; the most frequent among the hospital-admission group being: blood hypertension, pneumonia, diabetes mellitus, and the group who eventually died: pneumonia, cerebrovascular and neoplastic disease. PMID- 2103287 TI - [The partial inhibition of the growth hormone response to growth hormone releasing hormone after the administration of the calcium antagonist verapamil]. AB - The changes produced by administering a calcium channel antagonist on the releasing of growth hormone (GH) induced by the growth hormone-releasing factor (GHRF), are studied. The study was performed on 7 healthy males between 25 and 35 years old, fasting and in bed. We measured the release of GH after the intravenous administration of 250 micrograms of GHRF on 2 successive occasions; one baseline and the second after 3 previous continuous days of 240 mg/day of verapamil. There were no statistically significant differences between the basal concentrations of GH before and after the administration of verapamil. However, the response of GH to GHRF, measured as maximum increase (before verapamil: 12.5 +/- 5.3; after verapamil: 9.5 +/- 3.9 ng/ml and total increase (before verapamil: 29.6 +/- 12.4; after verapamil: 21.6 +/- 11.9 ng/ml) was significantly lower after verapamil produces a partial blockade of GH release induced by GHRF. PMID- 2103288 TI - [Acute pseudo-obstruction of the colon, a problem of old age. A study of 5 cases treated medically]. AB - Acute partial obstruction of the colon is a frequent complaint among elderly patients, this being the reason for the increase in incidence. 5 cases which were medically treated successfully are presented. The proper terminology is briefly discussed, describing the typical clinical features and the associated diseases which appear in 80-90% of cases. The diagnosis is basically clinical and plain abdominal X-Ray, barium enema and/or colonoscopy are the most helpful tests to make a differential diagnosis between mechanical and nonmechanical obstruction. An in-depth view on colonoscopy as a diagnostic and therapeutic method is presented. PMID- 2103289 TI - [Pneumonia in adults caused by the respiratory syncytial virus]. AB - Respiratory syncytial virus (RSV) usually affects children but sometimes affects a certain group of adults. A case of an 81 year old female with idiopathic thrombocytopenic purpura who had pneumonia caused by RSV is presented. The literature is reviewed as well as the most frequent clinical manifestations, diagnosis methods and treatment. PMID- 2103290 TI - [Atraumatic rupture of the spleen. A proposal of new attitudes. Apropos a case in brucellosis]. AB - A case of spontaneous spleen rupture during acute brucellosis, followed by clinical and ultrasound examinations until the natural resolution of the subcapsular hematoma, is presented. The causes of this complication are reviewed and a new classification is proposed, creating 3 groups of nontraumatic ruptures: spontaneous, with basal splenic disease and associated to other pathology. We highlight the several states of spleen ruptures--some with spontaneous resolution -and the utility of the radiological techniques to carry out a follow-up on them, which can in some cases help avoid surgical intervention. PMID- 2103291 TI - [The usefulness of biochemical markers of bone remodelling in the diagnosis and follow-up of Paget's disease of bone, primary hyperparathyroidism, tumoral hypercalcemia and postmenopausal osteoporosis. I. The markers of bone formation]. AB - Rapid detection of the exact changes in bone remodelling is exceptionally important. In this paper, the latest bone remodelling biochemical markers are reviewed. Some of them have already been used for a long time, and their utility has been widely demonstrated. The newest ones, in experimental stage, can be used as a complement to the others. The bone remodelling markers reviewed are: 1) Alkaline phosphatase; 2) osteocalcin; 3) Other noncollagen of bone matrix such as osteonectin, GLA-protein of the matrix, osteopontine and alpha 2-HS-glycoprotein; 4) Procollagenous and other collagenous peptides of the matrix (C terminal of type-I procollagen and urinary elimination of nondialysis hydroxyproline. Amongst the bone resorption markers studied are: 1) Calcium/creatinine urinary quotient; 2) Tartrate resistant acid phosphatase; 3) Urinary hydroxyproline; 4) Other substances derived from collagen disruption such as hydroxilysin glycoside, piridinolinic intermolecular bridges and the enzymatic activity of proline iminopeptidase. We endeavoured to collect all the most important references on the matter, especially those relating to Paget's disease of the bone, primary hyperparathyroidism, tumoral hypercalcemia and postmenopausal osteoporosis. PMID- 2103292 TI - [Cushing's syndrome due to a black adrenal adenoma]. PMID- 2103293 TI - [Cardiac tamponade: the first manifestation of pulmonary adenocarcinoma]. PMID- 2103294 TI - [Disseminated hematomas as the first manifestation of an aortic aneurysm]. PMID- 2103295 TI - [Septicemia in a patient wearing a transvenous pacemaker]. PMID- 2103296 TI - [Fasciola hepatica infection: apropos 2 cases]. PMID- 2103298 TI - [Alcoholism and the working population]. PMID- 2103297 TI - [Pseudohypoparathyroidism type Ib. Apropos a case]. PMID- 2103299 TI - [Malaria in Spain]. PMID- 2103300 TI - [Induced malaria in drug addicts? A real problem in our country?]. PMID- 2103301 TI - [Preventive medicine in the Anales de Medicina Interna]. PMID- 2103302 TI - [The characteristics of arterial hypertension in the population of a preventive medicine service]. PMID- 2103303 TI - [Diffuse fasciitis with eosinophilia and reactive thrombocytosis]. PMID- 2103304 TI - [Pseudotumoral adrenal insufficiency]. PMID- 2103305 TI - Intra-peritoneal administration of interleukin-1 beta induces impaired insulin release from the perfused rat pancreas. AB - Previous studies have demonstrated a stimulatory effect of interleukin-1 beta (IL 1 beta) on insulin and glucagon release from the perfused rat pancreas, accompanied by selective lysis of 20% of beta-cells as assessed by electronmicroscopy. However, we have not observed an inhibitory action of IL-1 beta on insulin release from the perfused pancreas as shown for isolated islets. To test whether periodical exposure of the endocrine pancreas to circulating IL-1 beta in vivo affects insulin release from the intact perfused pancreas, rats were treated with daily intraperitoneal injections of 4 micrograms IL-1 beta/kg or saline for 5 days. On day 5 the pancreata were isolated 2 h after the last injection and perfused from 0 to 72 min with 11 mmol/l D-glucose and from 72 to 84 min with 20 mmol/l D-glucose. Saline or IL-1 beta was added from 12 to 72 min. In pancreata from animals pre-treated with IL-1 beta glucose-stimulated as well as IL-1 beta potentiated glucose-stimulated insulin release was almost completely abolished. Furthermore, a decline in insulin release was observed at 11 mmol/l D glucose, in contrast to an increase in insulin release in controls. The total extractable insulin content in pancreata from IL-1 beta pre-treated rats was higher than in pancreata from saline-treated controls. In contrast to the inhibitory effect of in vivo administration of IL-1 beta on beta-cell function glucagon secretion was stimulated. These observations suggest that circulating IL 1 beta is an important modulator of alpha- and beta-cell secretory function in vivo and that IL-1 beta should be considered a contributory pathogenetic factor in the development of insulin-dependent (type 1) diabetes mellitus. PMID- 2103306 TI - Relationship between antibodies to dsDNA and to soluble cellular antigens and histologically defined glomerulonephritis in patients with SLE. AB - To better define the relationships between circulating autoantibodies and renal involvement in systemic lupus erythematosus (SLE), antibodies to both dsDNA and soluble cellular antigens were detected in sera from a large series of SLE patients. Significantly higher dsDNA binding activities and lower complement levels at onset were found in patients with renal disease; however, this was uniquely due to subjects with diffuse or focal proliferative glomerulonephritis. Patients with membranous nephropathy (MGN) showed very low dsDNA binding activities (6/9 of them being negative for dsDNA antibodies) and normal mean C3 and C4 levels. A comparison between patients with proliferative nephritis and patients without renal involvement with high dsDNA binding activities revealed significantly lower complement levels in the former group. No significant difference was observed in the prevalence of antibodies to soluble cellular antigens between patients with or without renal disease; however, nRNP antibody was two-fold more frequent in patients with MGN than in all other subgroups. This study highlights the close relationship between concurrently high anti-dsDNA and low complement levels and proliferative glomerulonephritis in SLE, and suggests that subjects with MGN may represent a subgroup of SLE patients showing peculiar serological features. Different mechanisms possibly involved in the pathogenesis of MGN in SLE are discussed. PMID- 2103307 TI - Longitudinal immunoblotting variations of auto-antibody reactivity of patients with systemic lupus erythematosus. AB - The purpose of this study was to examine longitudinally the different patterns of nuclear and cytoplasmic antigen recognition by sera from patients with SLE during clinical flare and remission using immunoblotting (IB) techniques. Serum samples (n = 150) were obtained from 35 SLE patients during a follow-up period averaging 4.7 years. Three patients (10 sera) were in complete remission: the IB pattern of these 3 patients remained unchanged; 32 SLE patients experienced one or more clinical flares: in 5 cases (20 sera) the IB analysis showed no detectable antibody. The following dominant IB patterns were seen in the remaining 27 active SLE patients: anti-Sm (n = 7), anti-Sm/RNP (n = 7), anti-SS-B and/or anti-Ro (n = 6), anti-histones (n = 5), anti-70 Kd (unidentified) (n = 2). No IB pattern was able to differentiate mild forms of SLE from severe cases. In 9 of 21 clinical flares, the serum IB pattern was not different from that of the patient's serum drawn during remission (3 severe and 6 mild flares). Diversity of the antibodies increased in 7 cases (5 severe, 2 mild flares); and a shift from one pattern to another was observed 5 times (2 severe, 3 mild flares). Twenty three subsequent remissions were studied: in 14 cases the IB profile was unmodified (5 severe, 9 mild SLE), and the diversity of the antibody narrowed in 4 cases (2 severe, 2 mild SLE). The IB pattern shifted from one pattern to another (2 severe, 4 mild SLE) in 5 instances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103308 TI - Eye muscle membrane reactive antibodies are not detected in the serum or immunoglobulin fraction of patients with thyroid-associated ophthalmopathy using an ELISA and crude membranes. AB - We tested sera and purified immunoglobulin (Ig) fractions from patients with autoimmune thyroid disorders (AITD), with and without ophthalmopathy, and normal subjects, for the presence of antibodies reactive with eye muscle membrane antigens in an optimized enzyme-linked immunosorbent assay (ELISA). We found no correlation between ELISA results and the presence or severity of ophthalmopathy in patients with AITD for either serum or Ig, and there were no significant differences between the mean values (+/- SE) for the three groups (AITD with ophthalmopathy, AITD without ophthalmopathy and normals) for either serum or Ig. In contrast Ig from 8 of 19 (45%) patients with thyroid-associated ophthalmopathy reacted with a 64 kDa eye muscle membrane antigen in SDS-polyacrylamide gel electrophoresis and Western blotting, while tests were positive in only one of the 8 patients with AITD without eye disease and in none of the 8 normal subjects. The presence of antibodies to a 64 kDa antigen in immunoblotting did not correlate with the levels of antibodies measured in ELISA. We conclude that the ELISA, incorporating a crude membrane fractions as antigen, is not useful as a clinical test for eye muscle autoantibodies. PMID- 2103309 TI - Pretreatment of human vascular smooth muscle cells with interleukin-1 enhances interleukin-6 production and cell proliferation (action of IL-1 on vascular smooth muscle cells). AB - Systemic vasculitis is an inflammatory disorder of blood vessels characterized by a perivascular mononuclear cell infiltration around the vessel and fibrinoid necrosis within vessel walls. Interleukin-1 (IL-1) is a multipotent inflammatory mediator and affects several properties of vascular cells. To determine whether IL-1 could contribute to the pathogenesis of vascular diseases, we examined the effect of IL-1 on B cell stimulatory factor-2/interleukin-6 (IL-6) production by cultured human vascular smooth muscle cells (SMC) and the proliferation of these cells. Supernatants of SMC stimulated IgM synthesis of human B cell line. SKW6 CL4 cells. This activity was increased (1.7 to 2.6-fold) when SMC were pretreated with IL-1 or calcium ionophore A23187 for 48 h, and was completely blocked by rabbit anti-human IL-6 antibodies. These IL-6 activities of the SMC supernatants were also assessed by using an IL-6 dependent murine hybridoma cell line. MH-60. BSF-2. In addition, we observed that pretreatment of SMC with IL-1 for 48 h stimulated growth of SMC during the 96 h incubations, as assessed by cell number (p less than 0.05). These results suggest that IL-1 may contribute to the pathogenesis of inflammatory and immunological vasculitis by the augmentation of IL-6 release and growth of SMC. PMID- 2103310 TI - Effects of iodide on class II-MHC antigen expression in iodine deficient hyperplastic thyroid glands. AB - The expression of major histocompatibility complex class II molecules (Ia antigen) has been analyzed by immunoperoxidase staining in thyroids of normal C3H mice, of iodine-deficient mice with a hyperplastic goiter and of mice during goiter involution induced by administration of either a high iodide dose (HID, 10 micrograms/day) for 0.5 to 8 days or a moderate iodide dose (MID, 1 microgram/day) or triiodothyronine (T3, 1 micrograms/day) for 2 days. In normal and in hyperplastic thyroids, few interstitial cells were Ia positive (monoclonal antibodies, mAb, M5/114, ER-TR3). Their number was unchanged when goiter involution was induced by MID or by T3, but was significantly increased (p less than 0.05) after HID. It was maximal at days 1 and 2 of involution, decreased thereafter but remained higher (p less than 0.05) than in controls after 8 days. The Ia positive cells were mainly macrophages and, to a lesser extent, dendritic cells. Macrophages were identified by their heterogeneous content and their numerous lysosomes. They were stained with anti-Mac-1 (M1/70) and anti-Mac-2 (M3/38) mAb. Dendritic cells were characterized by their slender cytoplasmic processes, indented nucleus and pale cytoplasm. They were positive for NLDC-145 and MIDC-8 mAb whose specificity for dendritic cells has been demonstrated in lymphoid organs. During the whole period of involution analyzed, Ia antigens were not expressed on follicular cells. Since macrophages and dendritic cells are known to be involved in the pathogenesis of immune disorders, the inflammation induced by administration of HID to iodine-deficient mice could be considered as the early step of an immunological reaction. PMID- 2103311 TI - The structure of thyroid autoantigens. PMID- 2103312 TI - Fibrin-dependent activation of plasminogen by a proteolytic digest of streptokinase. AB - Among four enzymatic digests of streptokinase (SK), the smallest peptide with plasminogenolytic activity was in a tryptic digest; it had a molecular weight of 29,000. A complex of this peptide, SK29, and human plasminogen hydrolysed human fibrin, but a complex of native streptokinase and human plasminogen hydrolysed both human and bovine fibrin. The complex with SK29 caused amidolysis of the synthetic substrate S-2251 in the presence of human fibrin, but was inactive in the presence of human fibrinogen, bovine fibrinogen or bovine fibrin. Analysis of the amino terminal sequence of SK29 indicated that cleavage by trypsin was on the carboxyl side of lysine, the 59th amino acid of streptokinase. These results suggest that the conformational changes caused by human fibrin formation resulted in the generation of an active site of human plasminogen by SK29. PMID- 2103313 TI - Coagulant and noncoagulant thrombin enzymatic activity on the endothelium. AB - The present study examines the role of antithrombin III (ATIII) and heparin in the inactivation of thrombin on rabbit aortae in vitro. Thrombin on the endothelium was functionally assayed with a synthetic chromogenic substrate (thrombins) or with fibrinogen (thrombinf), measured as the liberation of fibrinopeptide A. After incubation with thrombin, residual amounts were found on the endothelium. Surface-bound thrombinf constituted approximately one-half of surface-bound thrombins. Displacement of thrombin activity from the thrombin loaded endothelial surface was achieved with Polybrene. The thrombin could be quantitatively recovered in the Polybrene solution and equal amounts of thrombins and thrombinf were found. Incubation of endothelial segments with ATIII resulted in only a minimal uptake of ATIII on the surface but in a significantly increased capacity to inactivate thrombin, whereas incubation of the segments with heparin alone had the opposite effect. The effect of ATIII could be inhibited by prior incubation with Polybrene or by a subsequent incubation with heparin. It is concluded that the vessel wall content of ATIII is one determinant for the capacity to inhibit thrombin and that ATIII is bound to glycosaminoglycans on the vessel wall since it could be displaced by heparin. PMID- 2103314 TI - Hormonal regulation of the acute haemostatic response to stress. AB - Acute physical stresses such as major surgery, insulin-induced hypoglycaemia and exercise are associated with acute increases in circulating concentrations of factor VIII and increases in fibrinolytic activity. The mechanisms involved in producing these responses are partly under hormonal control and there is evidence that the neurohormones adrenaline and arginine vasopressin mediate some of the changes. Adrenaline infusions in man produce increases in both factor VIII and fibrinolysis and the rise in factor VIII is blocked by pretreatment with propranolol. Receptor blockade with propranolol also prevents the rise in factor VIII associated with hypoglycaemia to support the view that adrenaline is an important mediator under these circumstances. The pituitary antidiuretic hormone, arginine vasopressin, produces similar changes in haemostasis at plasma concentrations above those required for its renal effects, but within the range commonly seen during certain physical stresses. However, studies in clinical models that produce increases in vasopressin without a concomitant increase in adrenaline concentrations show enhanced fibrinolysis but no change in factor VIII. Thus it seems that adrenaline and vasopressin have a role in the regulation of haemostasis associated with stress, although the role of vasopressin in the regulation of factor VIII is open to question. PMID- 2103315 TI - Factor VIIa in the treatment of haemophilia. AB - Recombinant FVIIa is being developed for treatment of haemophiliacs with antibodies against FVIII/FIX. rFVIIa was shown to be haemostatically active in haemophilia A and B dogs as well as in 20 haemophilia patients (one haemophilia B and 19 haemophilia A patients). Thirteen patients were treated for life threatening bleedings and nine at surgery (dose: 60-90 micrograms/kg q 3-4 h). One patient underwent synovectomy in a knee joint under the cover of rFVIIa as the sole coagulation factor without any problems. One patient with FXI deficiency was successfully treated at an orchidectomy. The haemophilia B patient was treated in association with a compartment syndrome (surgical fasciotomy) with a complete haemostasis. He later uneventfully underwent skin grafting. Two CNS bleeds, a severe mouth bleed were treated as well as an extensive nasopharyngeal bleed in a patient with an acquired inhibitor against FVIII. Shortening of the prothrombin time as well as of the APTT was seen. No side-effects were observed. It is speculated whether FVIIa in complex with not only tissue factor but also phospholipids exposed at the site of injured cells directly activates FXa and thereby the final common pathway of the coagulation cascade. PMID- 2103316 TI - Hereditary protein C deficiency: a review of the genetics, clinical presentation, diagnosis and treatment. AB - Protein C (PC) is the central component of a major antithrombotic regulatory system with both anticoagulant and profibrinolytic properties. A deficiency of PC is one of several hereditary abnormalities of haemostatic proteins that have been described in patients with a propensity for thromboembolic complications. Major morbidity is often seen in these patients. The various aspects of hereditary PC deficiency in terms of clinical presentation, genetics, diagnosis and treatment of both homozygous and heterozygous states will be presented. In heterozygous deficiency, the levels of plasma PC are usually between 35% and 65% of normal, whereas the majority of normal individuals have levels between 70% and 130%. PC deficient patients usually develop venous thrombotic complications between the ages of 15 and 40 years with a high incidence of DVT and pulmonary embolism. The majority of thrombotic lesions appear to develop spontaneously; others are associated with trauma, surgery or pregnancy. Treatment of symptomatic patients is initial heparin therapy followed by coumadin. After multiple thrombotic events, lifelong oral anticoagulant therapy is necessary. The potential complications of treatment are coumadin-induced skin necrosis, heparin-induced thrombocytopenia and bleeding. Homozygous PC deficiency, a rare but fatal hereditary condition, manifests itself with massive DIC and purpura fulminans in the newborn period. Effective treatment for these infants can be instituted with either oral anticoagulant therapy or PC replacement. The heterozygous deficiency of PC is similar to that found in other inherited disorders in that several genetic mechanisms are responsible for the expression of the disease. Both quantitative and qualitative decreases in PC exist, the former being type I deficiency and the latter, type II. The best initial diagnosis of either form involves a clotting (functional) assay while differentiation between the two also requires an antigenic (immunological) assay. Autosomal inheritance with significant variable penetrance is found with profound clinical implications. In summary, PC deficiency is one of a group of inherited disorders termed hereditary thrombotic disease, which may have serious implications for patient morbidity and mortality. PMID- 2103317 TI - Multiple, relapsing thrombosis in a young man with primary thrombocytosis. AB - We report the case of a relatively young man with multiple and fatal thrombosis associated with essential thrombocythaemia. The clinical and laboratory examinations performed before his death were in agreement with the diagnostic criteria proposed by PVSG. The autopsy revealed myocardial infarction and pulmonary embolisms. This case suggests that young patients with primary thrombocytosis should be treated with antiplatelet agents in spite of the absence of other thrombotic risks. PMID- 2103318 TI - Multiple transient ischaemic attacks and a mild thrombotic stroke in a HIV positive patient with anticardiolipin antibodies. AB - Antiphospholipid antibodies (APA) have been reported to be associated with thrombosis in systemic lupus erythematosus (SLE) and in many other clinical groups. However, although these antibodies have been identified in a substantial number of patients infected with the human immunodeficiency virus (HIV), in this case an association with thrombosis has not been evident. We describe a patient with HIV infection who had anticardiolipin antibodies (ACA) but no lupus anticoagulant (LA) who had recurrent transient ischaemic attacks (TIAs) and a mild stroke. PMID- 2103319 TI - The role of Ca2+ in cell killing. PMID- 2103320 TI - Review of the current status of calcium and thiols in cellular injury. PMID- 2103321 TI - The role of calcium in lethal cell injury. PMID- 2103322 TI - Formation of secondary ozonides from the reaction of an unsaturated phosphatidylcholine with ozone. AB - Phosphatidylcholines are significant components of pulmonary surfactant in the alveolar region of the lung, where they play a major role in lung function due to their surface tension reducing properties. However, separation and the direct identification of many of the primary products of reaction of phosphatidylcholines with inhaled pollutant gases has not been possible until recently due to the lack of suitable analytical techniques, so that compounds such as fatty acid methyl esters generally have been used as analogues for the phospholipids. We report here the first isolation and identification of the products of reaction of ozone with one of the unsaturated components of lung surfactant, beta-oleoyl-gamma-palmitoyl-L-alpha-phosphatidylcholine (OPPC), using a combination of high-performance liquid chromatography, fast atom bombardment mass spectrometry, and Fourier transform infrared, ultraviolet absorption, and nuclear magnetic resonance spectrometry as well as gas chromatography. The products are shown to be the cis and trans secondary ozonides of the parent phosphatidylcholine, analogous to those previously observed by other researchers in the reactions of the simple fatty acid methyl esters with ozone. This also appears to be the first report of fast atom bombardment mass spectra of these phospholipid secondary ozonides. The implications of this work for the inhalation of ozone, formed in photochemical smog, are discussed. PMID- 2103323 TI - The contribution of N-oxidation to the metabolism of the food-borne carcinogen 2 amino-3,8-dimethylimidazo[4,5-f]quinoxaline in rat hepatocytes. AB - The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, a potent bacterial mutagen and rodent carcinogen formed in low quantities in cooked meat and fish, was studied in freshly isolated rat hepatocytes. Ten metabolites were characterized by various spectroscopic methods. Sulfamate formation was the major route of metabolism in hepatocytes of untreated rats whereas ring-hydroxylated sulfuric and glucuronic acid conjugates were major metabolites in animals pretreated with the enzyme inducers Aroclor-1254, beta-naphthoflavone, or isosafrole. The formation of a mutagenic metabolite through N-oxidation, 2 (hydroxyamino)-3,8- dimethylimidazo[4,5-f]quinoxaline (HNOH-MeIQx), was an important route of metabolism in hepatocytes of pretreated animals. Its metastable derivative, the N-hydroxy-N-glucuronide, also was detected. The nitro derivative of MeIQx, a direct-acting bacterial mutagen, was readily detoxified by glutathione transferase, forming a conjugate where the thiol group of glutathione displaced the nitro moiety. Low but detectable levels of N-acetyltransferase activity were observed for MeIQx and sulfamethazine in hepatocytes. HNOH-MeIQx and 4-(hydroxyamino)biphenyl (HNOH-ABP), a recognized human carcinogen, displayed acetyl coenzyme A dependent DNA binding in hepatic cytosol assays. Sulfamethazine decreased the DNA binding of HNOH-MeIQx in hepatocytes, suggesting a competition for acetyltransferase. However, the binding of HNOH-MeIQx to DNA in hepatocytes was independent of sulfotransferase since inhibitors of this enzyme, 2,6-dichloro 4-nitrophenol (DCNP) and pentachlorophenol (PCP), did not diminish DNA binding. In contrast, binding of HNOH-ABP to DNA was not decreased by sulfamethazine, but binding was diminished by both sulfotransferase inhibitors. From these inhibition experiments it appears that a major route of binding of HNOH-MeIQx to DNA in hepatocytes is mediated through O-acetyltransferase while a significant portion of HNOH-ABP bound to DNA is catalyzed by sulfotransferase. PMID- 2103324 TI - A new one-step method for the preparation of 3',5'-bisphosphates of acid-labile deoxynucleosides. AB - A method is described for preparing 3',5'-bisphosphates of labile deoxynucleosides. Under strictly anhydrous conditions, pyrophosphoryl tetrakistriazole apparently forms a ring structure bridging the 3'- and 5' hydroxyl groups of deoxynucleosides, since upon the addition of water the ring opens and the 3',5'-bisphosphate is formed. Due to the presence of triethylamine no acid is generated at any time so that the entire procedure is in neutral solution. The bisphosphates of N2,3-ethenodeoxyguanosine, O2-ethyldeoxythymidine, and O4-methyldeoxythymidine, all of which are acid-labile, were prepared in good yield without degradation. Other modified bisphosphates prepared include O6 benzyldeoxyguanosine and 1,N6-ethenodeoxyadenosine, as well as those of unmodified deoxyguanosine and thymidine. Characterization was by 31P NMR and UV spectroscopy. Both 5'p(dT)p3' and 5'p(dG)p3' were substrates for RNA ligase, further proving the structure of the phosphorylated compounds. PMID- 2103325 TI - Stereoselectivity in the microsomal conversion of N-nitrosodimethylamine to formaldehyde. AB - The possibility that N-nitrosodimethylamine (NDMA) might be metabolized preferentially at either the syn (relative to the nitroso oxygen) or the anti methyl group has been examined by comparing the rates of formaldehyde production when unlabeled NDMA, its fully deuteriated analogue (NDMA-d6), and (Z)- or (E)-N nitrosomethyl(methyl-d3)amine (NDMA-d3) were incubated in turn at concentrations of 0-2.4 mM with acetone-induced rat liver microsomes. The Km values for the conversion of (Z)- and (E)-NDMA-d3 to formaldehyde were identical to each other within experimental error (32 +/- 2 and 35 +/- 1 microM, respectively) but different from those for NDMA (24 +/- 6 microM) and NDMA-d6 (116 +/- 3 microM); similar Vmax values were observed for the four isotopic variants [7.5-8.1 nmol/(mg of protein.min)]. The observed similarity of kinetic parameters for (Z)- and (E)-NDMA-d3 suggested that the isotopic composition of the methyl group is an energetically more important determinant of its rate of oxidation at the NDMA demethylase active site than is its orientation relative to the nitroso oxygen atom. The absence of syn vs anti stereospecificity was confirmed via product isolation studies, in which the formaldehyde generated from each of the four isotopomers was trapped as the dimedone adduct and assayed for deuterium content by mass spectrometry; again, a strong preference for metabolism at CH3 vs CD3 regardless of stereochemistry was observed, though the data on CH2O generation suggested that there may be a slight net excess of anti attack. The results indicate that the microsomal enzymes employed display little regioselectivity in metabolizing the syn vs anti methyl groups of NDMA. PMID- 2103326 TI - Structure-activity relationship for the intrinsic hepatotoxicity of dinitrotoluenes. AB - The relation of various structural parameters to hepatotoxic potential was investigated by using six dinitrotoluene (DNT) isomers and isolated rat hepatocyte suspensions as the biological test system. DNT-induced hepatotoxicity was found to correlate with an inhibition of protein synthesis and an increase in lactate dehydrogenase (LDH) release but not with lipid peroxidation. With each isomer, protein synthesis inhibition was the most sensitive indicator of cytotoxicity. Regardless of the indicator, ortho- and para-substituted isomers were more hepatotoxic at the same concentration than meta-substituted isomers. High-performance liquid chromatograms (HPLC) on samples at 4 h revealed significant quantities of reduced metabolites in the medium. However, increased lipid peroxidation (formation of thiobarbituric acid reactants or evolution of ethane) in the cells was not consistently demonstrated. log EC50 for protein synthesis inhibition and log EC20 for LDH release were linearly correlated with the C atomic charge on the ring carbons bearing the nitro substituents by using molecular orbital (MNDO calculations) theory. The relation was used to predict the hepatotoxic potentials of untested nitrotoluenes, and the predictions were verified to a first approximation by using three trinitrotoluene isomers. PMID- 2103327 TI - Synthesis, characterization, and solution properties of ras sequences modified by arylamine carcinogens at the first base of codon 61. AB - The complementary pentadecamers d(5'-TACTCTTCTTGACCT) (strand A) and d(5' AGGTCAAGAAGAGTA) (strand B), which span a portion of the mouse c-Ha-ras protooncogene centered around codon 61, were synthesized by using standard beta cyanoethyl phosphoramidite chemistry and characterized by sequence analysis. Strand A, containing a sole guanine at the position corresponding to the first base of codon 61, was modified with N-acetoxy-N-(trifluoroacetyl)-2-aminofluorene or its 4-aminobiphenyl analogue. In both cases only the corresponding N (deoxyguanosin-8-yl)arylamine adduct was formed, as judged from HPLC and UV analyses conducted after enzymatic hydrolysis of the modified oligomers. Nonmodified and modified pentadecamers were annealed with strand B. Cooperative melting transitions were observed with all samples, thus indicating the formation of stable duplexes. Melting temperatures decreased in the order nonmodified duplex greater than 2-aminofluorene-modified duplex greater than 4-aminobiphenyl modified duplex, which indicated destabilization of the helical structure upon incorporation of the adducts, with 4-aminobiphenyl having the greatest effect. Circular dichroism spectra of all duplexes were characteristic of an overall right-handed B-type conformation, with no major conformational differences being detected between the two arylamine-modified oligomers. PMID- 2103328 TI - Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P 450IIE1. AB - Human cytochrome P-450IIE1 has been implicated in the oxidation of a number of substrates, including protoxins and -carcinogens. To date, no drugs have been identified that are exclusive substrates for the protein and are applicable for use as noninvasive probes of the in vivo function of the enzyme in humans. Chlorzoxazone was found to be oxidized only to 6-hydroxychlorzoxazone in human liver microsomes. Results of steady-state kinetics are consistent with the view that only a single enzyme catalyzes the reaction. The microsomal reaction was strongly inhibited by rabbit anti-P-450IIE1 and, in a competitive manner, by known P-450IIE1 substrates. Rates of chlorzoxazone 6-hydroxylation in different human liver microsomal preparations were well correlated with levels of immunochemically measured P-450IIE1 and rates of (CH3)2NNO oxidation. Chlorzoxazone 6-hydroxylation was also found to be catalyzed by purified human liver P-450IIE1. These results provide strong evidence that P-450IIE1 is the primary catalyst of chlorzoxazone 6-hydroxylation in human liver. Rates of chlorzoxazone 6-hydroxylation vary considerably among human liver samples, and chlorzoxazone 6-hydroxylation may have potential use as a noninvasive probe in estimating the in vivo expression of human P-450IIE1 and its significance as a risk factor in the toxicity and carcinogenicity of a number of solvents, nitrosamines, and drugs. PMID- 2103329 TI - On the mechanism of toxicity of illudins: the role of glutathione. AB - Illudin M and illudin S, antitumor sesquiterpenes from Omphalotus illudens, have been found to react with thiols in a pH-dependent manner. The optimum pH values for reaction of illudin M with methyl thioglycolate, cysteine, and glutathione were 5.8, 5.6, and 6.1, respectively, and pseudo-first-order rate constants at 25 degrees C (10-fold excess of thiol) were 44 x 10(-3), 11.5 x 10(-3), and 11.3 x 10(-3) min-1. In all cases, thiol added to the alpha, beta-unsaturated ketone giving an unstable intermediate. Subsequent loss of the tertiary hydroxyl and opening of the cyclopropane ring afforded a stable aromatic product. The toxicity of illudin S to HL60 cells was increased by lowering glutathione levels in the cells and vice versa. General toxicity and antitumor activity of illudins are discussed in the light of these results. PMID- 2103331 TI - Signals involved in interleukin 1 synthesis and release by lipopolysaccharide stimulated monocytes/macrophages. PMID- 2103330 TI - Metabolism and mutagenicity of dibenzo[a,e]pyrene and the very potent environmental carcinogen dibenzo[a,l]pyrene. AB - Dibenzo[a,l]pyrene (DB[a,l]P) is one of the most potent carcinogens ever tested in mouse skin and rat mammary gland. DB[a,l]P is present in cigarette smoke and, presumably, in other environmental pollutants. Metabolism and mutagenicity studies of this compound compared to the weak carcinogen dibenzo[a,e]pyrene (DB[a,e]P) can provide preliminary evidence on its mechanism of carcinogenesis. The mutagenicity of DB[a,l]P, DB[a,e]P, and benzo[a]pyrene (BP) was compared in the Ames assay with Aroclor-induced rat liver S-9. BP was the strongest mutagen. In strain TA100, DB[a,l]P and DB[a,e]P were marginally mutagenic. In strain TA98 both compounds were mutagenic, and DB[a,l]P induced more than twice as many revertants as DB[a,e]P. The mutagenicity of DB[a,l]P does not correlate with its carcinogenicity, since DB[a,l]P is a much stronger carcinogen, but a much weaker mutagen, than BP. The NADPH-supported metabolism of DB[a,e]P and DB[a,l]P was conducted with uninduced and 3-methylcholanthrene-induced rat liver microsomes. Metabolites were analyzed by reverse-phase HPLC and identified by NMR, UV, and mass spectrometry. Uninduced microsomes produced only traces of metabolites with either compound. The major metabolites of DB[a,l]P with induced microsomes were DB[a,l]P 8,9-dihydrodiol, DB[a,l]P 11,12-dihydrodiol, 7-hydroxyDB[a,l]P, and a DB[a,l]P dione. The metabolites of DB[a,e]P with induced microsomes were DB[a,e]P 3,4-dihydrodiol, 3-hydroxyDB[a,e]P, 7-hydroxyDB[a,e]P, and 9-hydroxyDB[a,e]P. Some of these metabolites are very useful in assessing possible pathways of activation in the initiation of cancer. PMID- 2103332 TI - The molecular basis for the generation of the human soluble interleukin 2 receptor. AB - Using an enzyme-linked immunosorbent assay (ELISA) employing two monoclonal antibodies recognizing distinct epitopes on the interleukin 2 receptor (IL2R) alpha chain (Tac molecule), we previously demonstrated that activated lymphocytes release a soluble interleukin 2 receptor molecule (sIL2R) in vitro and in vivo. The sIL2R is biochemically and structurally related to Tac, but its precise origin and functional role remain to be defined. We report here that a single IL2R cDNA is sufficient to direct the synthesis of both cell-associated and soluble released IL2R molecules. Northern analysis of IL2R cDNA transfected L cell lines revealed the presence of mRNA species unaccounted for by known transcription termination or internal splice sites. Nevertheless, S1 nuclease digestion studies failed to detect alternately spliced mRNA transcripts that specifically lack transmembrane or cytoplasmic domains and which may encode a secreted IL2R molecule. Therefore sIL2R does not appear to be the product of a unique post-transcriptional splicing event. In the absence of any post translational modifications, sIL2R is most likely generated by enzymatic cleavage and release of cell surface Tac. This proteolytic release of Tac may be but one example of a common cellular mechanism for regulating the membrane expression of cell surface molecules. PMID- 2103333 TI - Optimal collection of blood samples for the measurement of tumor necrosis factor alpha. AB - We have examined how delayed separation of plasma from cells affects the recovery of recombinant human tumor necrosis factor alpha (rhTNF alpha) from whole blood. Storage of heparinized whole blood samples at room temperature for 1 hr results in a significant (p = 0.036) fall in recovery of plasma TNF alpha from 788 +/- 119 pg/mL to 472 +/- 77 pg/mL, measured by specific enzyme-linked immunosorbent assay (ELISA). Storage of whole blood samples at 4 degrees C for 1 hr reduces but does not prevent the fall in recovery of plasma TNF alpha: 725 +/- 82 pg/mL at time 0, 472 +/- 81 pg/mL after 1 hr, p = 0.038. Recovery of bioactive TNF alpha (cytotoxocity for L929 cells) after 1 hr at room temperature is also significantly reduced from 576 +/- 139 pg/mL to 450 +/- 154 pg/mL, p = 0.036. Studies with 125I-rhTNF alpha confirmed the fall in plasma activity and revealed a rapid commensurate increase in 125I-rhTNF alpha activity in the cell fractions. We recommend that clinical samples for the measurement of cytokines should be kept at 4 degrees C and separated rapidly (within half an hour) before storing the plasma at -70 degrees C. PMID- 2103334 TI - In vivo inhibition of tumor growth of B16 melanoma by recombinant interleukin 1 beta. I. Tumor inhibition parallels lymphocyte-activating factor activity of interleukin 1 beta proteins. AB - Seven daily intratumoral injections of human recombinant interleukin 1 beta (rHu IL 1 beta) inhibit the growth of B16 melanoma in syngeneic female C57BL/6 mice. Inhibition was dose dependent and ranged from 36% to 93%. Other routes of injection of rHu-IL 1 beta (intramuscular, intraperitoneal, intradermal) inhibited tumor growth but to a lesser degree (27% to 50%). Two different rIL 1 beta s, one a mutein of rHu-IL 1 beta (Glu-4) and the other one murine IL 1 beta (rM-IL 1 beta), were tested in the tumor inhibition model. rM-IL 1 beta inhibited tumor growth at lower concentrations than did rHu-IL 1 beta and also had enhanced IL 1 activity in the thymocyte assay in vitro. The mutein of rHu-IL 1 beta (Glu 4) had significantly reduced in vitro IL1 activity and did not inhibit tumor growth. No cytotoxic or cytostatic effects of rHu-IL 1 beta were observed in in vitro assays. These results suggest that rHu-IL 1 beta has antitumor activity in vivo that is probably not due to its direct effects on B16 cells but rather is mediated by secondary effects of IL 1 beta. PMID- 2103335 TI - Differential priming for endotoxin-induced circulating cytokine production by tumor necrosis factor-alpha and interleukin 1 beta. AB - In unprimed mice, a single injection of a non-lethal dose of lipopolysaccharide (LPS) produced a rise in tumor necrosis factor (TNF) and interleukin 6 (IL 6) activities. Peak serum concentrations were attained, respectively, 1.5 hr and 2.5 hr after the challenge. Pretreatment with recombinant human TNF-alpha (rHuTNF) had a priming effect for enhanced production of both serum cytokines without any change in kinetics. The enhancement was more pronounced in the TNF (15-fold) than in the IL 6 (4-fold) response. Recombinant murine TNF caused a comparable increase in LPS-induced cytokine release. In contrast, comparable pretreatment with another macrophage-derived cytokine, recombinant human interleukin 1 beta (HuIL1-beta), revealed a negative effect on LPS-induced TNF release whereas IL 6 in the blood reached levels similar to those found after priming with rTNF. Moreover, when administered in combination with rHuTNF, rHuIL1-beta inhibited the priming effect on TNF autocrine production. PMID- 2103336 TI - Interactions of intermediate filaments with cell structures. AB - Intermediate filaments (IF) are unique components of the cytoskeleton of most eukaryotic cells. Also the nuclear lamins are now recognized to be IF-like proteins, providing the nucleus with a putative skeleton for chromatin attachment. Immunofluorescence and whole-mount electron microscopic studies reveal that IF form a cytoplasmic network that surrounds the nucleus and extends to cell surface, as 'mechanical integrators of cellular space'. It seems however unlikely that IF in the cell accomplish a merely structural role, considering the diversity of IF proteins and the complex regulation of their gene expression. In this work we primarily present electron microscopic data that points to the presence of interactions between IF and several cellular components, namely the nucleus, plasma membrane, other cytoskeletal elements, cytoplasmic organelles and ribonucleoproteins. Although the functional significance of such interactions remains to be demonstrated, assumptions like involvement of IF in information transfer or cytoskeleton-dependent control of gene expression represent attractive hypothesis for future research. PMID- 2103337 TI - Computation of a three dimensional image of a periodic specimen from a single view of an oblique section. AB - We describe here a method for computing a three dimensional map of a periodic specimen from a single electron micrograph of an obliquely cut section. Neighbouring areas of such an image display successively the contents of the unit cell of the structure. The reconstruction procedure can be considered in two steps. The first step involves restacking of successive areas to produce an image akin to that produced by serial section reconstruction. The resolution normal to the section would, at this stage, be limited by the thickness of the section, since the micrograph represents a projection of the density in the section. However, because of the periodic nature of the specimen, the image contains redundant information, which can be used in an attempt to deconvolute the section thickness and thus produce improved resolution normal to the section. The computation can be carried out directly with the densities or more conveniently, particularly for three dimensional crystals, by using Fourier transforms. The approach, which is most powerful when the section is thin, is insensitive to the collapse of the section caused by electron irradiation. Striated muscle provides particularly suitable specimens for such analysis and we present, as examples, computed maps of the M-band of fish muscle and of insect flight muscle in rigor. PMID- 2103338 TI - EM visualization of nucleocytoplasmic transport processes. AB - The nuclear envelope is strategically located between the nucleoplasm and cytoplasm, and, as such, can play a major role in controlling cellular activity by regulating the exchange of macromolecules between these two compartments. The nuclear pore complexes, which are located within circular areas formed by fusion of the inner and outer membranes of the envelope, represent the primary, if not the exclusive, exchange sites. Individual pores are able to function in both protein import and RNA efflux from the nucleus. Translocation of macromolecules occurs by either passive diffusion or facilitated transport through central channels within the pores. The functional size of the diffusion channel is approximately 9 to over 12 nm in diameter depending on the cell type. The width of the transport channel varies as a function of the number and effectiveness of the specific nuclear targeting signals contained within the permeant molecule. The maximum diameter of the channel can be over 26 nm. Nucleocytoplasmic exchanges can be regulated either by (1) differences in the properties of the transported molecule (molecular size and signal content) or (2) changes in the properties of the pore complexes, which can effect both diffusion and transport. PMID- 2103339 TI - The present state of two-dimensional crystallization of membrane proteins. AB - This review summarizes the present literature on two-dimensional crystallization of membrane proteins, with emphasis on the technical aspects. It includes all the intrinsic membrane proteins that have been crystallized after solubilization. Four general ways of making crystals are described in detail. Furthermore, suggestions for improving crystallization conditions are presented. PMID- 2103340 TI - Intracellular signal transduction pathways in sponges. AB - Sponges are the lowest multicellular eukaryotic organisms. Due to the relatively low specialization, and concomitantly the high differentiation and dedifferentiation potency of their cells, the sponge cell system has proven to be a useful model to study the mechanism of cell-cell adhesion on molecular levels. Results of detailed biochemical and cell biological studies with the main cell adhesion molecules, the aggregation factor (AF) and the aggregation receptor, led to the formation of the modulation theory of cell adhesion. The events of cell adhesion are contigent on a multiplicity of precisely coordinated intracellular signal transduction pathways. Using the marine sponge Geodia cydonium we showed that during the initial phase of cell-cell contact the AF causes a rapid stimulation of the phosphatidylinositol pathway, resulting in an activation of protein kinase C and a subsequent phosphorylation of DNA topoisomerase II. As one consequence of these processes, the cells undergo a phase of high DNA synthesis. However, at later stages, the AF loses its mitogenic activity; this function is then taken over by the matrix lectin. During this switch, the lectin receptor associates in the plasma membrane with the ras oncogene product. The description of these processes is subject of this review article. PMID- 2103341 TI - Muscle necrosis caused by snake venoms and toxins. AB - Snake bite is often associated with localised soft tissue necrosis. Less frequently victims may suffer extensive muscle damage leading to rhabdomyolysis and the loss of muscle-specific protein. This review describes the organisation and structure of mammalian skeletal muscle, and its response to myotoxic venoms and to isolated pure myotoxic venom fractions. The clinical reports of muscle damage in man following snake bite are discussed, and the various classes of myotoxic toxins are introduced. Muscle damage caused by the toxins is next described, particular emphasis being placed on the correlation between muscle pathology seen at the light level and the morphological changes seen at the level of the electron microscope. Where known, those subcellular components of the muscle fibre that are especially sensitive to assault, and those components that appear to be spared, are identified. The relevance of the selective sparing of some components to the regenerative capacity of the skeletal muscle is considered. PMID- 2103342 TI - Cold stage design for high resolution electron microscopy of biological materials. AB - Both the number and range of applications of cryotechniques in transmission electron microscopy are increasing rapidly. In some cases, most notably the determination of protein structure by electron crystallography, progress has been limited by the performance of commercially available cryo stages. We review the design and performance criteria for stages which will be necessary for wide applicability in high resolution studies of biological specimens. The important criteria include an operating temperature below -140 degrees C with a low rate of contamination of the specimen, ability to tilt to 60 degrees, and perhaps most important, good resolution as judged by an effective modulation transfer function of 0.8 at 0.35 nm. Most applications also require an effective cryotransfer system. Up until now, most work in high resolution electron crystallography has been accomplished with laboratory-built stages which meet some, but not all, of these criteria. The availability of cold stages which fully meet criteria will allow the rapid expansion of high resolution studies by electron microscopy in structural biology. PMID- 2103343 TI - Two structural states of the vertebrate Z band. AB - Ultrastructural analysis of the vertebrate Z band suggests that two reversible states of a single intricate lattice are essential for the contractile process. The two structural states of the Z band lattice (ss and bw) have been described in cross section in skeletal and cardiac muscle in different physiological states. The lattice responds to active tension but resists passive deformation. Changes in Z band form and dimension are correlated with cross-bridge binding. Two-dimensional image processing techniques show enhanced structural features that vary with the observed changes in lattice dimension. All projected images from all lattices show an approximate four-fold symmetry. Each image reveals differences in the appearance of axial filaments which enter from opposite sides of the Z band and cross-connecting filaments of similar curvature which appear to connect each axial filament to four nearest axial filaments. In the ss images, the apparent diameter of cross-cut axial filaments and the Z band interaxial filament spacing are smaller than in bw images. Cross-connecting filaments appear to overlap in the region half-way between axial filaments in ss images. We conclude that the Z band is an essential and dynamic part of the sarcomere, uniquely suited to transmit tension while maintaining dimensions appropriate for cross-bridge interaction. PMID- 2103344 TI - Imaging of protein molecules--towards atomic resolution. AB - This review discusses some of the recent developments in high resolution imaging of biological molecules. Electron micrographs of unstained biological molecules never show the resolution or contrast that would be predicted. Movements in the specimen caused by radiation damage, and possibly charging of the specimen are the most significant factors in the reduction of image contrast of these radiation-sensitive specimens. Until these limitations are overcome it is unlikely that the structures of biological molecules will be determined to the resolutions to which they are preserved. The causes of contrast loss in images are discussed in a quantitative manner and the use of crystalline paraffin as a model for radiation-sensitive specimens in general is described. Procedures for improving the contrast in images of biological molecules are described, including the new method of spot-scan imaging. Possible future developments, including high resolution imaging of single particles, are discussed. PMID- 2103345 TI - Formation of the astral mitotic spindle: ultrastructural basis for the centrosome kinetochore interaction. AB - The formation of the astral mitotic spindle is initiated at the time of nuclear envelope breakdown from an interaction between the replicated spindle poles (i.e. centrosomes) and the chromosomes. As a result of this interaction bundles of microtubules are generated which firmly attach the kinetochores on each chromosome to opposite spindle poles. Since these kinetochore fibers are also involved in moving the chromosomes, the mechanism by which they are formed is of paramount importance to understanding the etiology of force production within the spindle. As a prelude to outlining such a mechanism, the dynamics of spindle formation and chromosome behavior are examined in the living cell. Next, the properties of centrosomes and kinetochores are reviewed with particular emphasis on the structural and functional changes that occur within these organelles as the cell transits from interphase to mitosis. Finally, a number of recent observations relevant to the mechanism by which these organelles interact are detailed and discussed. From these diverse data it can be concluded that kinetochore fiber microtubules are derived from dynamically unstable astral microtubules that grow into, or grow by and then interact laterally with, the kinetochore. Moreover, the data clearly demonstrate that the interaction of a single astral microtubule with one of the kinetochores on an unattached chromosome is sufficient to attach the chromosome to the spindle, orient it towards a pole, and initiate poleward motion. As the chromosomes move into the region of the forming spindle more astral microtubules become incorporated into the nascent kinetochore fibers and chromosome velocity decreases dramatically. During this time the distribution of spindle microtubules changes from two overlapping radial arrays to the fusiform array characteristic of metaphase cells. PMID- 2103346 TI - Immunocytochemistry of the cell nucleus. AB - This electron microscopic review addresses in situ immunocytochemistry of the mammalian cell nucleus with special reference to the use of autoantibodies, which are the major source of antinuclear antibodies. The localization of many key nuclear antigens is documented and immunocytochemical data are related to the major functional processes of transcription and processing of RNA and to replication of DNA. PMID- 2103347 TI - Structural diversity and dynamics of microtubules and polymorphic tubulin assemblies. AB - Tubulin, the main protein of microtubules (MTs), has the potency of forming a variety of other assembly products in vitro: rings, ring-crystals, C- and S shaped ribbons, 10 nm fibres, hoops, sheets, heaped sheets, MT doublets, MT triplets, double-wall MTs, microtubules, curled ribbons, and paracrystals. The supramolecular subunits of all of them are the protofilaments which might be arranged either parallel to the axis (e.g., in MTs, ribbons) or curved (e.g., in hoops, microtubules). There is strong evidence that in the second case the protofilaments have an inside-out orientation compared to MTs. All assembly products mentioned are described structurally and their relevance to the in vivo situation is considered. Moreover, MTs and the other assemblies undergo permanent changes. These dynamics occurring in both individual assemblies and assembly populations are discussed from the structural point of view. PMID- 2103349 TI - In vitro immunization for the production of human monoclonal antibody. PMID- 2103348 TI - Human anti-DNA idiotype (16/6 idiotype): pathogenic role in autoimmunity. PMID- 2103350 TI - Human T-T cell hybridomas: development and applications. AB - Human T-T cell hybrids are developed by fusing activated T lymphocytes exhibiting a desired immunological function or producing soluble factors with a human tumor T cell line with the objective to immortalize the T cell properties of interest. Mutagenized human tumor T cell lines, deficient for the enzyme hypoxanthine guanine phosphoribosyl transferase have been used for the development of T-T cell hybrids. Unfused tumor cells are removed by using appropriate selection media. Certain of these media contain components (such as thymidine) that inhibit the growth of the hybrids. A different method involves the use of tumor T cell lines chemically treated, before the fusion, with irreversible biochemical inhibitors. This treatment eliminated any unfused cells of the T cell line. Recently, a method has been developed for the generation of human T-T cell hybrids without the use of mutagenized or chemically treated tumor T cell lines. Hybrids are selected on the basis of their ability to form colonies in soft agar, and their hybrid nature is confirmed by HLA typing and functional tests. The human lymphoblastoid cell lines used did not form colonies in agar. Hybrids developed by this method exhibit excellent growth characteristics and increased stability. A large number of human T-T cell hybrids producing growth, differentiation or immunoregulatory factors have been developed. Certain hybrids exhibiting immunological functions requiring direct cell-cell contact have been developed also. The advantages of using T-T cell hybrids over other methods for immortalizing T cell functions or lymphokine production are summarized. Also, the obstacles in developing T-T cell hybrids are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103351 TI - Production of human monoclonal antibodies to B lymphocyte cell surface antigens by in vitro immunization and human-human hybridoma technology. AB - We attempted to produce human monoclonal IgM antibodies to class II HLA antigens by in vitro immunization of human splenocytes with affinity purified HLA or irradiated whole lymphoblastoid B cells using the adjuvant muramyl dipeptide and IL-2. Two fusions where affinity purified HLA was used to stimulate the in vitro immunization produced no hybrids secreting antibodies against the stimulating antigen. However, 13.1% of 381 hybrids from eight fusions were positive by CELISA when whole cells were used to immunize. These antibodies were reactive with a wide range of cell types and were not directed to HLA. It proved difficult to characterize them, possibly because of low affinity. One reacted in Western blots with a 200 kD antigen, but this was exceptional. Most bound to a small percentage of cells in flow cytometry and did not lyse target cells in cytotoxicity assays. Control fusions were performed and similar antibodies were obtained from 2.6% of 235 hybrids. These data suggest that in vitro immunization using the protocol outlined can increase the frequency of some antibodies, but that they may represent a very primitive lineage which does not have the specificity and affinity required to prove useful as diagnostic or therapeutic agents. PMID- 2103352 TI - Generation and characterization of human monoclonal antibody HMD4 against ovarian carcinoma and the study of radioimmunoimaging in nude mice. AB - Lymphocytes from regional lymph nodes of patients with ovarian carcinoma were immortalized by fusing them with a nonsecreting cell line of murine myeloma (Sp2/0-Ag14). By early cloning and recloning a hybrid cell line, named HMD4, was established. It has secreted human IgG for more than 15 months stably. Chromosome analysis corresponded with the characterization of human-mouse hybridoma. Large quantities of ascites were obtained after hybrid cells injection into the primed nude mice. Human IgG of light chain was detected and purified from the ascites. Twenty-six of 43 (60.5%) epithelial ovarian cancers were positively stained with HMD4 by ABC immunoperoxidase methods while nonepithelial ovarian cancers and almost all benign tumors and normal tissues were negative. The molecular weight of the antigen recognized by HMD4 was 55KDa determined by Western blotting. 131I labeled HMD4 was administered intraperitoneally to nude mice bearing human ovarian epithelial adenocarcinoma; 131I labeled normal human IgG and normal murine IgG were used as controls. Measurements of T/NT and T/B ratios of 131I HMD4 were done. Radioimaging showed HMD4 clearly localized on tumor regions at 48 and 72 hours and the biodistribution and metabolism of the labeled HMD4 corresponded with the images. The above results indicate that HMD4 was specific to ovarian carcinoma, a hopeful clue for clinical applications. PMID- 2103353 TI - Limited sampling models for HA-1A IgM monoclonal antibody. AB - In this study, limited sampling models for HA-1A human IgM monoclonal antibody were developed to predict the area under the concentration time curve from timed serum concentrations. Patients were administered 15 minute infusions of 25 mg (11 patients), 100 mg (15 patients), and 250 mg (2 patients). A detailed pharmacokinetic analysis (eight time points) was performed to obtain the area under the curve for each of the 28 patients using a one-compartment model with the values normalized to a dose of 100 mg. Various models were then developed to estimate the area under the curve from one and two timed concentrations using regression analysis methodology. Of these models, four were determined to be of interest with coefficients of determinations ranging from 0.92 to 0.97. They performed quite well in predicting the area under the curve values with relative root mean squared predictive error of 7.1 to 10.8% and relative mean predictive error of -4.5 to + 6.9%. These models should be extremely useful in larger scale, Phase II/III studies of HA-1A in correlating the estimated area under the curve with various demographic data, toxicity, and efficacy. PMID- 2103354 TI - Binding and functional properties of a mouse-human chimeric monoclonal antibody of the human IgG1 subclass with specificity for human carcinomas. AB - Recombinant DNA techniques were utilized successfully to join the coding regions for the variable region of a mouse anti-tumor antibody (BA-Br-1) and the human IgG1 constant region for both the light and heavy chains. After insertion into a mouse myeloma host cell line, the chimeric genes were expressed successfully and the resulting antibody (ING-1) was purified. In this study, we describe biochemical, serological, immunohistochemical, and functional properties of the chimeric ING-1 antibody. Analysis of the synthesized antibody revealed that while it was similar in size to the mouse antibody, it had a different pI as determined by isoelectrofocusing. The flow cytometric binding profiles of the new molecule were found to be essentially identical to the parental mouse immunoglobulin. The specificity of the chimeric ING-1 and mouse BA-Br-1 antibodies were compared by extensive immunohistochemical analysis on human normal and tumor tissues. The chimeric antibody retained the same broad carcinoma binding activity, showing strong reactivity with greater than 90% of epithelial tumor tissues, as was previously observed for the mouse BA-Br-1 antibody. The chimeric and mouse antibodies also recognized the same selected normal tissues: primarily glandular epithelia, gastrointestinal mucosa, bile ducts, and thyroid follicles. Analysis of the biological function of the chimeric antibody revealed that it possessed ADCC activity against antigen-bearing tumor targets in vitro which was absent from the mouse form of the antibody. Competent effector cells could be either PBMCs from normal healthy donors, PBMCs from cancer patients receiving LAK/IL-2 therapy, or LAK cells prepared from cancer patients. Enhanced cytotoxicity even in the presence of LAK cell killing was noted with effector cells from the latter two sources. This contrasts sharply with the absence of activity in the same systems when the native murine antibody was used. The in vitro activation of cell dependent cytolysis observed with the chimeric antibodies when effector cells from both normal and tumor-bearing donors were used strongly suggests that comparable activity would be observed in vivo. These results, along with the broad carcinoma binding activity and minimal normal tissue reactivity, suggest that the ING-1 chimeric antibody may be useful in cancer therapy. The application of the ING-1 chimeric antibody for treatment of tumors thus offers a promising avenue for future research. PMID- 2103355 TI - Human monoclonal antibodies to nuclear antigens. AB - Human lymph node lymphocytes from cancer patients were fused with either the UC 729-6 or SHFP-1 human fusion partners. Resulting human-human hybridomas were tetraploid, expressed markers from both parent cells, and secreted approximately 1 microgram Ig/10(6) cells/ml/day. Immunofluorescence analysis of some of the human MAbs with a panel of normal and malignant cell lines revealed a staining pattern of only the nuclear region. One IgM secreting hybridoma, TLN1F4, derived from a teratocarcinoma lymph node, predominantly stained the nuclear regions of adherent tumor cell lines and no hematopoietic cell lines or normal fibroblasts. PLN3C8, an IgG1 secreting hybridoma, derived from a prostate carcinoma lymph node, predominantly stained the nucleolus of LnCap, a a carcinoma of the prostate cell line. CLN2E5, an IgM secreting human hybridoma, derived from a carcinoma of the cervix lymph node, predominantly stained both cytoplasmic and nuclear components to tumor cell lines and not normal fibroblasts or hematopoietic cell lines. These data suggest that the immune response occurring within regional draining lymph nodes is capable of recognizing nuclear-associated antigens. PMID- 2103356 TI - Immunodominant antigens of Streptococcus mutans in dental caries-resistant subjects. AB - Previously, we reported that dental caries-resistant subjects, who have significantly fewer Streptococcus mutans in whole saliva than caries-susceptible patients, have significantly higher levels of naturally occurring binding and neutralizing parotid salivary immunoglobulin A and serum immunoglobulin G antibodies to native S. mutans antigens than caries-susceptible patients. Recent animal studies indicated that the immunogenicity of swallowed S. mutans may be altered by either saliva-coating or stomach acid-denaturation. These results suggest a difference not only in the quantity of antibody to S. mutans, but also in the antigenic epitopes that caries-resistant subjects synthesize antibody to as compared with caries-susceptible patients. In the present report, sodium dodecyl sulfate-polyacrylamide gel electrophoresis/immunoblotting studies indicate that caries-resistant subjects produce salivary immunoglobulin A and serum immunoglobulin G antibodies to several different (molecular weight: 94, 80, 40, and 35 kilodaltons) as well as several similar (molecular weight: 67, 55, and 30 kilodaltons) S. mutans epitopes as compared to caries-susceptible patients. This provides additional confirmation for our previous binding and functional antibody studies, indicating that caries-resistant subjects synthesize antibodies of different specificities than caries-susceptible patients. This study supports the concept of immune regulation of dental caries by naturally occurring antibodies induced by swallowing S. mutans antigens in saliva. PMID- 2103357 TI - Preparation of human and murine monoclonal antibodies: antigens combined with or conjugated to lipopeptides constitute potent immunogens for in vitro and in vivo immunizations. AB - Lipopeptide analogues of bacterial lipoprotein constitute polyclonal B lymphocyte activators. Combined with or covalently coupled to antigens, they act as potent adjuvants. We could show that antigens (BSA-DNP, TNP-SRBC, saxitoxin, HIV-1 gp160(BH10303-329, EGFR516-523) combined with or coupled to the synthetic lipodipeptide N-palmitoyl-S-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-(R)-cysteinyl-s erine (P3CS) constitute active immunogens in vivo in mice. They were also able to induce an in vitro humoral immune response in the murine and human systems, and B lymphocytes thus activated were suitable for fusion. Thus, the antigens chaperonin/phytochrome, BSA-saxitoxin, histamine, HIV-1 gp160 (BH10(303-329)), HIV-1 gp160 (RF316-341)), and HIV-2 p17 (ROD111-121) combined with or conjugated to P3CS could be used for in vitro immunization followed by the preparation of murine and human monoclonal antibodies. Our novel immunization procedure offers reproducibility, high antibody titers often after one immunization, lack of toxicity of the adjuvants, easy chemical preparation of the conjugates in mg amounts, and the applicability of the conjugates for screening for the antibodies obtained. PMID- 2103358 TI - Cell surface phenotype, cytokines, and antibody gene expression in immortalized human B cell lines. AB - In an attempt to gain some insight into the many factors influencing antibody gene expression in human B cell lines, we have examined in detail the relationship between cell surface phenotype, cytokines, and the growth and antibody-producing capacity of a panel of immortalized human B cell lines. The cell panel comprised lines secreting either high or low titers of antibodies against Rhesus D, hepatitis B surface, and tetanus toxoid antigens. All the transformed cell lines exhibited a cell surface phenotype characteristic of well differentiated peripheral blood cells strongly expressing CD23 and CD38 while weakly expressing CD10 and CD21. There was no obvious relationship between the antibody-body-secreting and proliferative capacity of the cell lines and their cell surface phenotype. Antibody secretion by the cells was rarely improved by the addition of a wide range of doses of recombinant IL-2, IL-4, or IL-6. In addition, such treatment frequently inhibited proliferation. Supernatants from some of the cell lines promoted the growth of unrelated cell lines but failed to influence antibody production. Such supernatants contained the highest concentration of IL-1, TNF beta, TGF beta, and soluble CD23. In contrast, the heterohybrid supernatant which inhibited cell growth secreted low levels of these cytokines. None of the cell lines secreted detectable amounts of IL-2, IL-4, INF gamma, or GCSF. There was no obvious relationship between cytokine production and antibody secretion. Finally, LPS had a slight but variable effect on antibody secretion but failed to influence cell growth. PMID- 2103359 TI - Pokeweed mitogen-stimulated human lymphocytes fused to LICR-2 (HMY2) generate human-human hybridomas producing monoclonal IgG antibodies reactive to human breast carcinoma and malignant melanoma. AB - Human-human hybridomas were generated using pokeweed mitogen-stimulated lymphocytes from the regional lymph nodes of cancer patients by fusion to the LICR-2 human myeloma cell line. A total of 35 fusions, using the regional lymph node lymphocytes of cancer patients, resulted in hybrid growth in 23% of wells plated with 21 IgG ELISA positive clones, 6 of which have maintained stable human monoclonal antibody production. Mononuclear cells were separated on Ficoll-Paque and grown for 3-4 days in 1% pokeweed mitogen and fused to the LICR-2 human myeloma cell line. Human-human hybridoma producing membrane reactive IgG antibodies have been isolated and react to the following cancers: breast; melanoma. Twenty-seven fusions from 8 breast carcinoma patients resulted in 13 ELISA positive IgGs, 3 of which were stable after cloning. A total of 5,071 wells were plated after polyethylene glycol fusion with resultant hybrid growth in 1210 wells (24% hybrid growth) after hypoxanthine-aminopterin-thymidine selection. In 8 fusions using regional lymph node lymphocytes of other types of cancer, including 6 fusions using lymphocytes from malignant melanoma patients, there were 1,580 wells plated with positive growth in 20% of the wells (311 wells). Of these, 8 clones were ELISA positive and 3 stable clones all producing IgG anti melanoma antibody were isolated. The overall hybrid frequency was 43 x 10(-7) fused lymphocytes (39 x 10(-7) non-breast and 45 x 10(-7) breast). A total of 21 IgG-producing clones were identified to crude membranes of allogeneic tumor cell lines and stable antibody production was achieved for 6 (29% stable clones).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103360 TI - Analysis of factors affecting human hybridoma production. AB - Human hybridomas were produced by fusion of the GM 4672 cell line with lymphocytes from the peripheral blood, spleen, and bone marrow of patients with systemic lupus erythematosus. Lymphocytes were also obtained from normal human fetal liver of 12 weeks' gestation. The influence of anatomical source, fusion ratio, pre-stimulation with pokeweed mitogen, HLA match, and disease activity at the time of fusion was studied. Supernatants were screened for immunoglobulin secretion and binding to DNA, cardiolipin, poly(ADP-ribose), and histones by enzyme-linked immunoassay. A total of 28 fusions from 14 donors and 6 fusions with fetal lymphocytes were performed. The spleen was found to be the most efficient source of lymphocytes, with a fusion ratio of 1:1 resulting in a maximum yield of 27 clones/10(7) lymphocytes fused. HLA matching was a factor influencing the outcome with HLA A2 matching being the most important. Pre stimulation with pokeweed mitogen did not improve the fusion frequency, and fusions using lymphocytes from patients with active disease were only marginally more successful. Over 95% of clones secreted immunoglobulin; autoreactivity was found against DNA, histones, cardiolipin, and poly(ADP-ribose). All hybrids with autoreactivity secreted IgM. PMID- 2103361 TI - Potential role of PHA in producing human monoclonal thyroid autoantibodies of different subclasses. AB - A human monoclonal autoantibody to thyroglobulin (Tg) of subclass IgG2 was developed by fusing a mouse myeloma with Tg antibody secreting Epstein-Barr virus (EBV)-infected B lymphocytes from a Hashimoto patient. Subsequent studies showed that EBV-infected B lymphocytes from this patient synthesized IgG2 Tg antibody while unfractionated blood lymphocytes cultured with pokeweed mitogen secreted IgG1, IgG2, and IgG4 Tg antibodies in amounts proportional to those present in the patient's serum. To investigate this discrepancy further, we cultured EBV infected lymphocytes from blood, lymph nodes, and thyroid tissue in medium alone and with increasing concentrations of PHA. In individuals with thyroid autoantibodies predominantly of subclass IgG1, PHA enhanced the levels of total Tg antibody synthesis without affecting the IgG subclass distribution. However, in patients with serum autoantibodies of subclasses IgG1, 2, and 4, the increased levels of total Tg antibody synthesis were associated with increased amounts of thyroid autoantibodies of all of these subclasses; in some instances IgG1 and IgG4 autoantibodies were only synthesized in cultures containing PHA. These observations suggest that addition of the T-cell mitogen PHA to cultures of EBV infected lymphocytes may ensure activation of B-cell precursors committed to synthesizing the IgG subclasses characteristic of serum antibody in the lymphocyte donor. Since Tg antibodies of subclasses IgG2 and IgG4 recognize different epitopes on Tg, the ability to produce human monoclonal antibodies of different IgG subclasses may simultaneously ensure the development of antibodies to different epitopes on the same antigen. PMID- 2103362 TI - Comparison of metastatic properties of a variety of mouse, rat, and human cells in assays in nude mice and chick embryos. AB - We have previously developed an assay to measure experimental metastatic ability of cells following intravenous injection into chorioallantoic membrane (CAM) veins of naturally immune deficient chick embryos. Here we compare metastatic properties of different cell types (ras-transformed and control NIH 3T3, LTA, and 10T1/2; melanoma; and glioma) from several species (mouse, rat, human), using chick embryos and the more commonly-used immune deficient host, nude mice. We found a good correlation between the two assays. Both hosts have advantages and disadvantages in assessing metastatic properties. We conclude that the chick embryo assay is a useful alternative host for experimental metastasis studies. This assay correlates well with and is less costly than assays using nude mice. PMID- 2103363 TI - Lignified materials as potential medicinal resources. II. Prevention of pathogenic bacterial infections in mice. AB - Antibacterial activity was demonstrated when ddY mice were intraperitoneally infected with E. coli or P. aeruginosa two days after a single ip-injection of a hot-water or alkaline extract obtained from lignified materials, such as chips of slash pine, Douglas fir, tallow wood, and two shelf fungi. Lignified material is a promising medicinal resource for the prevention and/or treatment of pathogenic microbial infection. PMID- 2103364 TI - Improved preparation technique of cervical carcinoma for flow cytometric DNA analysis with tissue disintegration in hydrochloric acid. AB - An one-step procedure using a nuclear isolation medium containing propidium iodide has been found to be a suitable preparation technique for flow cytometric DNA analysis in breast cancer samples. In the case of cervical squamous carcinoma, a pretreatment with HCl seems to be a methodological improvement. One advantage with the HCl modification is that some "false" near-diploid cell populations are abolished. These "false" G0/G1 peaks may represent diploid nuclei with a different stainability for propidium iodide compared to normal diploid nuclei. The HCl treatment has, furthermore, the advantage of increasing the elution of nuclei (mean factor of 4.0), especially non-diploid nuclei from higher differentiated squamous carcinomas. PMID- 2103365 TI - In vivo destruction of canine lymphoma mediated by murine monoclonal antibodies. AB - The effect of murine anti-canine lymphoma monoclonal antibodies (MAbs) on tumor cell lysis by thioglycolate activated murine macrophages in vitro and tumor growth inhibition in athymic mice was studied. All IgG1 and IgG2a MAbs tested were able to promote specific destruction of canine lymphoma 17-71 cell line by activated macrophages. A correlation between higher ADCC activity and MAb isotype was not clearly evident. In vivo IgG2a and IgG1 MAbs inhibited the growth of canine lymphoma. These results suggest that MAbs of IgG type have potential in immunotherapy of dogs with lymphoma since they have high tumoricidal activity in vivo. PMID- 2103366 TI - Variations in regenerative growth of mouse liver following partial hepatectomy. AB - Liver regeneration after 35% or 70% hepatectomy of the mouse was studied. Significant variations in the pattern of regeneration were demonstrated within the same mouse strain, sex, age and under identical experimental conditions. In all the experiments there were large individual variations, and in some experiments significant differences between litters of the same age were seen. Liver DNA synthesis at 48 h after 35% hepatectomy in females, in experiments done at different times of the year, showed seasonal fluctuations, with high values in the winter and low values in the summer. The low values in the summer correlated with a shift of the DNA synthesis peak, which occurred later in the summer than in the winter. PMID- 2103367 TI - Banding studies in Canis familiaris. II. Nucleolar organizer regions and NOR association. AB - Nucleolar organizer regions (NORs) in the female dog karyotype are presented. Eight autosomes Nos. 5, 8, 14, 16, 19, 21, 32, and 37 showed active NORs. We observed a high incidence (50%) of metaphases with NOR association. PMID- 2103368 TI - Murine mycotic placentitis produced by intravenous inoculation of conidia from Aspergillus fumigatus. AB - Primipregnant BALB/cABom mice were challenged intravenously with 1 x 10(5) Aspergillus fumigatus conidia on day 10 of pregnancy. Histopathological examination of the foeto-placental units and extrauterine organs from the mice revealed hyphal growth restricted to the foeto-placental unit. In the foeto placental unit the growth of hyphae was first established on Reicher's membrane next to the periphery of the placental disc. Subsequently hyphae spread along and through the extrafoetal membranes, finally reaching the foetus. In the terminal stage of infection mycosis also ensued in the placental discs. In conclusion, A. fumigatus was found to have a propensity for infecting the murine foeto-placental unit, resulting in mycotic placentitis. This series of events seems comparable to the progression of the spontaneous disease in cattle. Consequently, the pregnant mouse seems applicable as an animal model for the study of mycotic placentitis due to A. fumigatus, which in most countries is of great importance in cattle breeding. PMID- 2103369 TI - Radiosensitivity of different human tumor lines grown as xenografts determined from growth delay and survival data. AB - Four human tumor lines were grown as xenografts in nude mice to determine whether xenografts derived from different types of tumors would show tumor-type dependent differences in response to single-dose irradiation, and whether these differences, paralleled clinical behavior. Xenografts from a neuroblastoma, a squamous cell carcinoma, a melanoma and a lung adenocarcinoma were studied in terms of growth delay and tumor control dose (TCD50). To exclude an immunoreaction of the host in the radiation response of the tumor xenografts, the tumor lines were tested for their growth in immunosuppressed Wistar rats. No differences in growth of xenografts in either immunodeficient mice or immunosuppressed rats were observed. Both growth delay and local tumor control as expressed by cure correlated well with clinical behavior of the tumor types of origin. This study demonstrates that radiosensitivity of different human tumor lines can be evaluated in terms of growth delay and tumor control dose50 when they are grown as xenografts. To exclude immune reactions, proper controls should be included. The sensitivities established from these evaluations parallel clinical behavior, thus offering a tool for analysis of human tumor radiosensitivity of histologically different tumor types. PMID- 2103370 TI - Effects of prolonged administration of neurotensin, arginine-vasopressin, NPY, and bombesin on blood TSH, T3 and T4 levels in the rat. AB - Adult female rats were i.p. infused (Alzet osmotic minipumps) with neurotensin (NT, 2 micrograms/rat/day for 7 days), arginine-vasopressin (AVP, 2 micrograms/rat/day for 8 days), bombesin (BM, 0.75 microgram/rat/day for 7 days) or injected with neuropeptide Y (NPY, 0.5 microgram/rat twice a day for 4 days). NT infusion increased absolute and relative thyroid gland weight and decreased serum T4 level, while serum TSH and T3 levels remained unchanged. AVP treatment increased thyroid gland weight and serum TSH and T4 levels and a similar effect was induced by prolonged BM infusion. On the other hand, NPY administration had no effect either on thyroid gland weight or on serum TSH, T4 and T3 levels. Results of the present study thus clearly demonstrate a potent stimulatory action of AVP and BM on thyroid gland function and suggest that this effect is mediated by the pituitary gland. On the contrary, prolonged NT infusion decrease serum T4 level while NPY had no effect on thyroid gland function. PMID- 2103371 TI - Immunological reactivity to a mycobacterial fraction is associated with nonspecific suppression of immunological responsiveness in vivo. AB - Previously reported studies revealed that spleen cells from BALB/c mice immunized against a methanol extraction residue (MER) fraction of tubercle bacilli are defective in the in vitro generation of antibodies to SRBC and in allogeneic responsiveness against C57BL spleen cells. We now show that mice repeatedly immunized with MER also exhibit a depressed capacity to respond to antigenic stimulation in vivo. Thus mice repeatedly injected with MER were impaired in their ability to react to antigenic stimulation by SRBC and by C57BL spleen cells. Impairment in the response to SRBC immunization was expressed at the level of delayed-type hypersensitivity (DTH) as well as of antibody production. The response of MER hyperimmunized mice to contact sensitization with dinitrofluorobenzene (DNFB) was not impaired, but the lymph node cells of DNFB sensitized animals had a depressed ability to respond to in vitro stimulation by the monovalent hapten dinitrobenzene sulfonate (DNBS). The present findings indicate that extensive exposure to an immunogenic immunomodulating mycobacterial fraction can lead to a depressed responsiveness to unrelated antigenic stimulation. PMID- 2103372 TI - DNA ploidy analysis of invasive bladder cancer by flow cytometry. AB - Refinement in the treatment of invasive bladder cancer requires improved methods to predict the biologic behavior of tumors. Although DNA ploidy analysis represents an initial application of flow cytometry, it has proved to be a clinically useful test. Flow cytometric DNA ploidy analysis is compared to conventional prognostic indicators, and its current status in the management of patients with invasive bladder cancers is discussed. PMID- 2103373 TI - Segmental liver resection with linear stapling device. An experimental study on pigs. AB - Segmental liver resection was performed in 14 pigs. The pigs were randomized either to resection with conventional finger fracture technique or resection with linear stapling device (TA-90R, US Surgical Corporation). The median time for resection was shorter in the stapled group, although the difference was not statistically significant. The median weight of the specimen was the same in both groups. The median postoperative Haemoglobin value was somewhat lower in the finger fracture resected group as compared to the stapler resected group, 82.5 g/l versus 87.5 g/l, but there was no statistically significant difference between the groups. Blood loss, estimated by counting the number of compresses, amounted to 188 ml for the finger fracture resected group and 181 ml for the stapler resected group. At the post-mortem examination there were no signs of bile leakage or postoperative blood loss in any of the operated animals. This study demonstrates that hepatic resection in the pig can be performed quickly and safely by using linear stapling device. Stapler resection was easier and somewhat quicker to perform than conventional hepatic resection. PMID- 2103374 TI - Chromosome preparation and high resolution banding (review). AB - Banding was developed and used to identify chromosomes in different species. Combined with ultrastructural studies, banding also provided insight into the substructure and organization of whole chromosomes. However, banded chromosomes prepared for light microscopic studies of intact metaphase plates are highly modified structures compared to native chromosomes and the high resolution R and G-banding techniques used today are only possible because several basic methods were standardized and combined. These techniques include: 1) The use of spindle inhibitors. 2) The use of hypotonic solutions. 3) The use of methanol acetic acid fixation and air- or flame dried slides. 4) The use of cell culture synchronization and modified Giemsa techniques. In connection with chromosome structure and selected banding studies, the present paper discusses these techniques and their applications to different topics in cytogenetics. PMID- 2103375 TI - Grafting of human autogenous keratinocytes cultured in vitro. AB - A rapid method of producing epithelial material suitable for covering skin defects after burns and avulsions is presented. In vitro grown keratinocytes suspended as single cells in human plasma were applied to the wound surface and covered with distended meshed xenograft. In this way it was possible in five clinical cases to obtain 25-80% epithelial coverage of wounds up to 200 times as wide as the donor area. PMID- 2103376 TI - Induction of cytotoxic factor in mice by lignified materials combined with OK-432 (Picibanil). AB - Intravenous administration of pine cone lignin-related substance (Fr. VI) significantly stimulated OK-432-elicited cytotoxic factor (CF) production in ICR mouse serum. The level of CF elicited after OK-432 administration peaked after 2 h and declined to basal level within 6 h. The CF productibility depended greatly on both dose and the interval between the administration of the Fr. VI and OK 432. Most natural and synthetic lignins, their degradation products, and polysaccharides, including pine cone hemicellulose fractions, had much weaker CF inducing (priming) activity. When Fr. VI was treated with NaCl02 to decompose the lignin portion, the priming activity was significantly reduced. The data suggest that the potent priming activity of Fr. VI might de a result of some conjugation between the lignin portion and other components including polysaccharides. PMID- 2103377 TI - Suppression of humoral antibody response during pregnancy in mice. AB - Fifty female BALB/cA mice were allocated to four groups. The mice of groups 1 and 3 were mated with male BALB/cA mice, whereas groups 2 and 4 served as unmated control groups. The mice of groups 1 and 2 received a primary immunization (100 micrograms ovalbumin in Freunds Complete Adjuvant) and the first booster immunization (100 micrograms ovalbumin in sterile saline) prior to mating. Eight days after mating, the mice of groups 1 and 2 received the second booster immunization. The mice of groups 3 and 4 received the primary immunization ten days after mating in group 3 and one booster injection five days later. At the end of the immunization period the individual serum titres of precipitating antibodies against ovalbumin were determined using a line-immunoelectrophoretic assay. Groups 1 and 2 showed no significant difference in the titres of precipitating antibodies against ovalbumin, indicating that the secondary antibody response was not generally suppressed during pregnancy. However, the pregnant mice of group 3 produced significantly lower titres of precipitating antibodies against ovalbumin as compared with the control mice of group 4 (P less than 0.01), demonstrating a suppression of the primary antibody response during pregnancy. PMID- 2103378 TI - Circadian variations in cell cycle phase distribution in a squamous cell carcinoma xenograft; effects of cisplatin and fluorouracil treatment. AB - Tumor tissue sampled at different points during a 24 hour period (08-08) from a xenografted squamous cell carcinoma of the head and neck was analyzed with flow cytometry. Statistically significant variations were found in the mean fraction of cells in the G1, S and G2 phases, the most pronounced variation occurring at 14 and 02 h. Histopathological examination showed no consistent circadian fluctuations in the fraction of cells in mitosis. Treatment with NaCl, cisplatin and fluorouracil was given at the time of most pronounced variation (i.e., 14 and 02 h). Toxicity was low. All animals in all groups survived treatment. All treated animals lost weight, but the initial weight loss was slightly greater and recovery delayed in the groups given cisplatin and fluorouracil at night. Tumor growth inhibition, as defined by the area under the growth curve, did not differ significantly between 14 and 02 h. PMID- 2103379 TI - In vivo model development of cisplatin-resistant and -sensitive A2780 human ovarian carcinomas. AB - The human ovarian carcinoma, A2780, and a derived cisplatin-resistant subline, A2780 cDDP, were developed as in vivo sc models in athymic mice. The tumor volume doubling time (TVDT) of both lines was calculated for tumors of between 250 mg and 1 gm, determined in both unselected (unstaged) tumor-bearing mice as well as mice whose tumors were (staged) between 50 and 200 mg when selected for observation. Similar mean TVDT (+/- SD) of 2.3 (+/- 0.5) and 2.7 (+/- 1.1) days for unstaged A2780 and A2780/cDDP tumors, respectively, and 2.2 (+/- 0.5) and 2.5 (+/- 0.7) days for staged A2780 and A2780/cDDP tumors, respectively, were observed. Each of the tumor settings just described was used to assess cisplatin's antitumor activity following ip and iv injections. Antitumor activity was expressed predominantly as gross log cell kill (LCK) and occasionally as percent inhibition. The staged tumor models used with iv cisplatin therapy evolved as the preferred system. Against staged A2780, the mean maximum LCK (+/- SD) associated with iv cisplatin therapy was 2.5 (+/- 1.0) based on 9 experiments, whereas with iv cisplatin versus staged A2780/cDDP yielded 0.5 (+/- 0.3) mean maximum LCK in 16 experiments. The sensitive and cisplatin-resistant staged tumor models were also used to evaluate three platinum analogs, carboplatin, iproplatin, and tetraplatin. All three cisplatin analogs were active (greater than or equal to 1 LCK) versus A2780 but not A2780/cDDP. Thus, the A2780 and A2780/cDDP tumor models demonstrated reproducible sensitivity and resistance, respectively, to cisplatin, and provide an in vivo system for evaluating cisplatin analogs. PMID- 2103380 TI - Polymerized albumin binding to serum in various liver diseases: its significance and relation to hepatitis B virus infection. AB - Sensitive and specific enzyme-linked immunosorbent assays (ELISA) were developed to detect separately the binding of polymerized human serum albumin (PHSA) to its antibody (A-PHSA) and to the hepatitis B surface antigen (HBsAg). A-PHSA was not detected in normal serum, whereas more than one-third to about half of sera from patients with acute liver cell injury showed this antibody. Frequency of A-PHSA positivity was low in chronic liver diseases, being relatively higher in those with continuing liver injury. A-PHSA detection was not related to seropositivity for HBsAg. PHSA binding of HBsAg positive sera showed a higher frequency of positivity in chronic carriers than acute hepatitis B. Of 172 asymptomatic HBsAg carriers, PHSA binding was demonstrated in 25 (15%), the frequency being significantly high if HBeAg was also present (84%). Binding was infrequent in sera having anti-HBe (2.9%) and in those negative for both HBeAg and anti-HBe (2.7%). Binding of HBsAg to PHSA was significantly higher than to human serum albumin (HSA). Immunoblotting of separated HBsAg components showed PHSA binding specifically to the high molecular weight peptide. PHSA binding in HBsAg positive serum may indicate the latter's infectivity as detected in a study of maternal fetal transmission, where it demonstrates 100% infectivity in HBsAg and HBeAg positive mothers. PHSA possibly mediates the attachment of the HBV to the hepatocyte and a competitive binding between A-PHSA with HBsAg for PHSA may modulate the course of HBV infection. PMID- 2103381 TI - Immunohistochemical studies on the localization of cancer associated antigens DU PAN-2 and CA19-9 in carcinomas of the digestive tract. AB - The immunohistochemical localization of DU-PAN-2 antigen and CA19-9 antigen in carcinomas of the digestive tract was studied using an immunoperoxidase technique. Staining for DU-PAN-2 antigen and CA19-9 antigen was observed in 104 (79%) and 96 (73%) of 131 carcinomas of the digestive tract, respectively. Diffuse staining (more than 20% of carcinoma cell stained) for DU-PAN-2 was detected in 14 of 21 (67%) pancreatic carcinomas and 11 of 19 (58%) carcinomas of the biliary tract (including cholangiocarcinoma). Diffuse staining for CA19-9 was detected in 15 (71%) of pancreatic carcinomas and nine (47%) of the carcinomas of the biliary tract. In colon carcinomas, no diffuse staining for DU-PAN-2 was observed, whereas diffuse staining for CA19-9 was found in 41%. There was a positive correlation between the differentiation degree (or grade) of the adenocarcinomas of the colon and the expression of CA19-9, but not that of DU-PAN 2. These immunohistochemical studies showed that DU-PAN-2 antigen is expressed diffusely in most cases of adenocarcinoma of the pancreas and biliary tract and is more specific for adenocarcinomas of the pancreas and biliary tract than CA19 9. PMID- 2103383 TI - Current concepts in the pathogenesis of Crohn's disease. PMID- 2103382 TI - Radio-immunoassay for formyl methionyl leucyl phenylalanine. II. Demonstration of an enterohepatic circulation of immunoreactive bacterial chemotactic peptides in man. AB - Bacterial chemotactic peptides (F-met-oligopeptides) are secreted by several species of commensal enteric bacteria and can be assayed by bioassay techniques in human colonic luminal fluid. We have previously demonstrated intestinal absorption and enterohepatic circulation of radiolabelled F-met peptides introduced into rat colon, and an eightfold increase in absorption and biliary excretion in rats with experimental colitis. This paper describes the application of a radio-immunoassay to measurements of formyl oligopeptides in human faecal dialysates, colonic and systemic venous blood and bile. All samples were fractionated by reverse-phase high performance liquid chromatography (HPLC) prior to assay. Immunoreactivity was found in faecal dialysates (5-700 nmol/L F-met-leu phe equivalents) and bile samples (3-150 nmol/L) from normal subjects. After HPLC fractionation, up to five distinct peaks of immunoreactivity were identified. One of these co-chromatographed with authentic F-met-leu-phe; the others probably represented either closely related peptides or peptides of different chain lengths originating from the same F-met-leu-phe precursor protein. Colonic venous blood from two patients with ulcerative colitis contained immunoreactive peptide (10-30 nmol/L) and substantial immunoreactivity was found in ileostomy fluid and bile from two patients with primary sclerosing cholangitis. These results suggest the presence of an enterohepatic circulation of bacterial F-met oligopeptides in man and provide a basis for studies of the role of such pro-inflammatory peptides in patients with inflammatory bowel disease and associated hepatobiliary disorders. PMID- 2103384 TI - Metabolic bone disease in primary biliary cirrhosis. PMID- 2103385 TI - Hepatic lymphatic system: structure and function. PMID- 2103386 TI - Percutaneous liver biopsy: a safe outpatient procedure. AB - Percutaneous liver biopsy with Menghini or Trucut needle as an outpatient procedure was performed on 159 patients over a 3.5-year period. No major complications were observed. Liver biopsy is recommended as an outpatient procedure, which would reduce the patient load on limited hospital beds and economize on the hospital resources. PMID- 2103387 TI - Stigmata of recent haemorrhage. PMID- 2103388 TI - Does diminished vascular responsiveness to norepinephrine account for the systemic hypotension of cirrhosis? PMID- 2103389 TI - Management of complicated acute pancreatitis: impact of computed tomography. AB - The usefulness of computed tomography (CT) in guiding the management of 43 patients who had a complicated clinical course of acute pancreatitis was retrospectively studied. The CT scans were performed when patients had persistent fever, leucocytosis, hyperamylasaemia, palpable abdominal masses or when there was organ failure. The CT scans showed normal findings in six patients, features of pancreatic abscess in three patients, pseudocysts in three patients and inflammatory masses (a mixture of sterile inflammation and necrosis) in 31 patients. Patients with pancreatic abscesses underwent emergency laparotomy, drainage and debridement; patients with pseudocysts had delayed drainage unless complication occurred; patients with normal CT scan or findings of inflammatory masses were managed conservatively. For patients undergoing conservative management, repeated CT scanning and percutaneous aspiration of the inflammatory mass was performed when pancreatic sepsis was strongly suspected. By this approach, basing on careful clinical and CT scan surveillance, five patients with pancreatic sepsis (pancreatic abscess and localized abscess collection in pseudocyst) underwent emergency surgery and four survived, while 25 patients with inflammatory masses were successfully managed conservatively and some who may have been operated on clinical grounds were spared unnecessary early debridement surgery. PMID- 2103390 TI - Induction and clinical utilization of lymphokine-activated killer cells in patients with gastrointestinal tract cancers. AB - In 18 patients with cancers of the gastrointestinal tract, lymphokine-activated killer (LAK) cell activity was studied and compared with that of healthy subjects. After cultivation with 10(3) iu/mL of recombinant interleukin-2, the cytotoxicity of patients' lymphoid cells was increased from 13.6 +/- 6.8% to 76.2 +/- 19.5% against Daudi cells and from 12.8 +/- 8.1% to 76.2 +/- 19.5% against K 562 cells. Based on these results, autologous LAK cells were given to patients. LAK cells injected into subdermal metastatic tumours demonstrated a significant inhibitory effect on tumour growth in comparison with that of control tumour nodules. Of four patients with metastatic tumours in the liver, to whom LAK cells were administered via the hepatic artery, tumour size was reduced by about 25% (minor response) in one patient, with a decrease of computerized tomography attenuation in the tumours occurring in the other three patients. PMID- 2103391 TI - Gastric acid response to modified sham feeding in patients with duodenal ulcer: is increased vagal tone the cause of basal acid hypersecretion? AB - In order to test the hypothesis that increased basal vagal tone causes basal acid hypersecretion in duodenal ulcer (DU), the effect of sham feeding on gastric acid secretion was studied in 26 patients with DU and 20 healthy controls. Basal acid output (BAO), sham feeding-stimulated acid output (SAO) and peak histamine stimulated acid output (PAO) were significantly higher in DU patients compared with healthy controls (P less than 0.01). The BAO/PAO ratio in DU patients (0.28 +/- 0.03) was not significantly different from that of healthy subjects (0.19 +/- 0.03), indicating that the higher BAO in DU patients group, as a whole, was due to a higher parietal cell mass. The basal subtracted response to sham feeding expressed as a fraction of secretory capacity [(SAO-BAO)/PAO], which correlates inversely with the basal vagal tone, was not significantly different in the patients and control subjects (0.27 +/- 0.03 versus 0.3 +/- 0.03; P greater than 0.05). Based on the data from the healthy controls, a ratio of BAO/PAO greater than 0.44 was defined as abnormal (using 95% confidence limits) and it indicated marked basal acid hypersecretion. Four of 26 DU patients had basal acid hypersecretion (that is, BAO/PAO greater than 0.44), but only two of them did not show an increase over their basal rate of secretion in response to sham feeding. All other DU patients, including two with marked basal acid hypersecretion, and all healthy controls showed an appreciable increase in their acid secretion in response to sham feeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103393 TI - Experience with MTBE as a solvent for common bile duct stones in patients with T tube in situ. AB - The postcholecystectomy patients who have a T-tube in situ offer a convenient route through the T-tube to perfuse solvents into the common bile duct (CBD) for dissolving any retained common duct stones. If successful, this approach is much simpler and cheaper than the usual therapeutic modality used for CBD stones, namely, endoscopic papillotomy. Thus a most potent cholesterol solvent, methyl t butyl ether (MTBE) was perfused through the T-tube into the CBD of five patients with retained common duct stones. The dose of the solvent varied, 1.5-5 mL 0.5-1 h, given 7-13 times amounting to a total of 20-66 mL. Instillation of MTBE in the T-tube was alternated with aspiration of the bile through T-tube. Only one patient showed complete disappearance of the bile duct stone following MTBE perfusion. Others did not show any appreciable response and had to be treated by endoscopic papillotomy (three patients) or mono-octanoin perfusion (one patient). Side-effects of MTBE perfusion included pain in the abdomen in all patients, somnolence and nausea/vertigo in two patients and the smell of ether on the breath in two patients. It is concluded that MTBE is not an effective agent for dissolution of retained CBD stones in patients with T-tube in situ. PMID- 2103392 TI - Regurgitation of bile acids in rat liver under bile drainage: quantitative analysis by taurine or ursodeoxycholate loading test. AB - In rats with an interrupted enterohepatic circulation of bile acids, levels of serum taurine-conjugated bile acids were increased significantly 3 h after intravenous administration of taurine. Similarly, serum taurine- or glycine conjugated ursodeoxycholic acid (UDCA) was increased significantly 2 h after UDCA administration. These findings suggested that the administered taurine or UDCA was taken up into hepatocytes and utilized to form conjugated bile acids, which were thereafter regurgitated into the systemic circulation from the liver. The proportion of regurgitated taurine-conjugated bile acids relative to total serum bile acids measured by taurine loading (30%) almost coincided with that of regurgitated taurine- or glycine-conjugated UDCA relative to total serum bile acids measured by UDCA loading (31.6%). Thus, the present study showed conclusively that at least 30% of serum bile acids are derived from newly conjugated bile acids that are regurgitated from the liver in rats with bile fistula. PMID- 2103394 TI - Primary sclerosing cholangitis: clinical and immunopathological review of 21 cases. AB - Twenty-one patients with primary sclerosing cholangitis were seen during 1979-87. The mean age at onset of disease was 51.7 years (range: 13-78 years) with a male: female ratio of 2.5:1. Six (29%) were asymptomatic at the time of diagnosis. Eleven patients (52%) had ulcerative colitis. Cholangiography demonstrated abnormalities limited to the intrahepatic ducts in 10 cases, with both intrahepatic and extrahepatic involvement in 11. Histological features on liver biopsy included: portal tract inflammation and cholestasis in all; paucity of bile ducts in 56%; piecemeal necrosis in 19% and cirrhosis in 6%. Circulating autoantibodies and elevated serum immunoglobulins were found in half of the patients and HLA-B8 was detected in 53%. A deficiency of circulating CD3 and CD8 cells was not found in the 12 patients tested. The mean follow-up was 51 months (range: 3-180 months). Three patients died from non-hepatic causes and another has received liver transplantation. A Kaplan-Meier curve predicted 70% survival at 72 months. PMID- 2103395 TI - Effect of verapamil on splanchnic haemodynamics in a portal hypertensive rat model. AB - To elucidate the effects of verapamil on splanchnic haemodynamics in rats with portal hypertension, verapamil was given at a low dose (0.2 mg/kg) and a high dose (2 mg/kg) to the rat model after portal vein ligation. Approximately 10% decrease in arterial pressure was caused by the low dose of verapamil, with significant decreases in cardiac output and portal venous inflow as well as reduced portal pressure; these were all indicative of a rise in portal vascular resistance. In contrast, the marked fall in both arterial pressure and cardiac output in the high dose, accompanied by a significant decrease in the portal pressure and the unchanged portal venous inflow, suggested a reduction in portal vascular resistance. This study shows that the acute effects of verapamil on portal hypertension may vary with the dosage used. These results also demonstrate that, since the therapeutic efficacy and safety of verapamil is only in a very limited range of dose, caution should be taken in its clinical use in the treatment of cirrhosis with portal hypertension. PMID- 2103396 TI - Yersinia enterocolitica: mechanisms of microbial pathogenesis and pathophysiology of diarrhoea. PMID- 2103397 TI - Oesophageal disease and non-cardiac chest pain. PMID- 2103398 TI - Haem in the gut. Part II. Faecal excretion of haem and haem-derived porphyrins and their detection. AB - Only a fraction of haem (ferroprotoporphyrin) finding its way into the gut lumen is absorbed; the major portion enters the colon. There, unabsorbed haem, together with any haem of haemoproteins shed directly into the colonic lumen as haemoglobin or other haemoproteins, are converted by bacteria to a range of haem derived porphyrins (HDP) lacking iron. This conversion is a slow and incomplete process and the amount converted in this way depends on colonic transit rate, site of bleeding and amount of luminal haem. As a consequence, faeces contain variable proportions of haem and HDP. The guaiac and tetramethylbenzidine tests give a qualitative index of faecal blood; they depend on the pseudoperoxidase activity of intact haem and cannot detect HDP. These tests perform better for large bowel bleeding than for more proximal bleeding. The fluorimetric HemoQuant assay quantitates both haem and HDP; it performs well for both proximal and distal bleeding. Neither type of test can allow for intestinal absorption of haem or HDP. Quantitation of gastrointestinal bleeding derived from measurement of faecally excreted haem and HDP is, therefore, likely to underestimate haem delivered into the gut lumen. In a given clinical situation, the choice of a haem dependent occult blood test must take into account the possibility of colonic conversion of haem to HDP and the possible value of quantitation as opposed to qualitative detection. PMID- 2103399 TI - Does adenomyosis of the gall-bladder cause symptoms? PMID- 2103400 TI - Laurence-Moon-Biedl syndrome accompanied by congenital hepatic fibrosis. AB - A 33 year old woman with mental deficiency, retinitis pigmentosa, obesity, and parental consanguinity (heredity) was diagnosed as having Laurence-Moon-Biedl syndrome. She also had diabetes mellitus, slight hepatic dysfunction, and hepatomegaly. Liver biopsy showed perilobular fibrosis and bile duct proliferation with cystic dilatation; these findings are consistent with those of congenital hepatic fibrosis. PMID- 2103401 TI - Hepatic veno-occlusive disease associated with comfrey ingestion. AB - A 23 year old man presented with hepatic veno-occlusive disease and severe portal hypertension and subsequently died from liver failure. Light microscopy and hepatic angiography showed occlusion of sublobular veins and small venous radicles of the liver, associated with widespread haemorrhagic necrosis of hepatocytes. The patient had been on a predominantly vegetarian diet and, prior to his illness, took comfrey leaves which are known to contain hepatotoxic pyrrolizidine alkaloids. Comfrey is widely used as a herbal remedy, but so far has only been implicated in two other documented cases of human hepatic veno occlusive disease. A possible causal association of comfrey and this patient's veno-occlusive disease is suggested by the temporal relationship of the ingestion of comfrey to his presentation, the histological changes in the liver and the exclusion of other known causes of the disease. PMID- 2103402 TI - Antipyrine elimination test as a guideline for selecting patients for transhepatic biliary drainage. AB - Antipyrine elimination halflife (AP t1/2) was studied in 18 patients with obstructive jaundice along with routine liver function tests 24-48 h before the expected time of percutaneous transhepatic biliary drainage (PTBD). To see if it is possible to predict the outcome of PTBD, various predrainage parameters were correlated with the postdrainage bilirubin clearance after 1 week of drainage. Predrainage AP t1/2 correlated best with bilirubin clearance (r = 0.775, P less than 0.01) compared with predrainage serum bilirubin, alkaline phosphatase and serum proteins/albumin. Eight patients had AP t1/2 less than 15 h, while 10 had AP t1/2 greater than 15 h. Patients with AP t1/2 less than 15 h had significantly faster recovery after PTBD than patients with AP t1/2 greater than 15 h. If PTBD can be restricted to those with AP t1/2 less than 15 h, the advantages of preliminary PTBD can be achieved with minimum complications. Thus, estimation of AP t1/2 may aid in the selection of patients with obstructive jaundice who are likely to benefit by preliminary biliary decompression. PMID- 2103403 TI - Chronic hepatitis with fatty change. AB - Ten patients with clinical features of chronic hepatitis showed on liver biopsy histologic evidence of chronic hepatitis plus predominantly moderate to severe fatty change. No patient had a history of excess alcohol intake, or prolonged intake of hepatotoxic drugs and steroids, and were not obese or malnourished. These cases differ from the reported cases of non-alcoholic steatohepatitis resembling alcoholic hepatitis as they occurred in relatively young health adults, predominantly males, who were not diabetic or obese. Mallory's hyalin in liver was absent in all cases. Ingestion of toxic substances was possible but no history was obtained to account for it. While these could be unusual cases of chronic non-A, non-B hepatitis, this can be only speculation until a serologic test for non-A, non-B hepatitis becomes available. Follow-up of eight patients for 1-3 years with liver biopsy showed that they had a relatively benign course with no evidence of progression to cirrhosis. PMID- 2103404 TI - Significance of hepatitis B core antigen in the liver in patients with chronic hepatitis B and its relation to hepatitis B virus DNA. AB - Liver biopsies from 52 patients with chronic hepatitis B were investigated for the presence and distribution of HBcAg and the results were compared with the status of hepatitis B virus deoxyribonucleic acid (HBV-DNA). The patients consisted of 37 men and 15 women, aged 16-55 years (mean = 34 years). Serum alanine aminotransferase (ALT) was elevated in 50 patients (range: 18-969 U/L; mean = 290 U/L). Serological testing showed HBsAg in all, HBeAg in 45 (87%), and HBV-DNA in 28 (54%). Liver biopsies demonstrated HBcAg in 35 (67%) patients. HBcAg was not only present in 31 of 45 (69%) patients who were seropositive for HBeAg, but also in four of seven (57%) with antibody to HBeAg (anti-HBe). In 28 of 35 (80%) patients with HBcAg in the liver, serum HBV-DNA was detected. However, no serum HBV-DNA was detected in 17 patients who had no detectable HBcAg in the liver. The distribution of HBcAg in the liver was rather cytoplasmic and nuclear than nuclear alone. Among 33 patients with cytoplasmic HBcAg in the liver, 15 (45%) had an evidence of acute exacerbation of hepatitis with marked ALT elevation (range: 168-894 U/L; mean = 385 U/L) and nine patients showed severe chronic active hepatitis and confluent necrosis, histologically. These results indicate that the presence of HBcAg in the liver correlates with the amount of circulating hepatitis B virus as quantified by serum level of HBV-DNA. The predominant cytoplasmic HBcAg in the liver may suggest the possibility of multiple episodes of acute exacerbation and more severe ongoing hepatitis during the clinical course. PMID- 2103405 TI - Auto-immune features in patients with idiopathic chronic active hepatitis who are seronegative for conventional auto-antibodies. AB - In patients with chronic active hepatitis (CAH), the absence of the conventional serum auto-antibodies (antinuclear, smooth muscle and liver-kidney microsomal) is often taken as evidence against an auto-immune aetiology and as indicative that the disease is unlikely to respond to immunosuppressive therapy. We report 12 British patients (11 female) who presented with histologically florid CAH (11 with cirrhosis or fibrosis and seven with ascites) but without significant titres of these antibodies or any other demonstrable aetiological feature (cryptogenic CAH), who have been followed up for a median of 5.25 years (range: 0.75-16 years). Ten had hypergammaglobulinaemia and/or specific elevations of serum IgG concentrations at presentation and five of 10 patients tested were found to have the HLA allotypes B8 and DR3. Remission was initially induced with prednisolone with or without azathioprine in all patients. Six patients subsequently relapsed on one or more occasions, either spontaneously while on maintenance therapy or during attempts to withdraw corticosteroids, and required increases or reintroduction of immunosuppressive therapy to regain disease control. Retrospective analysis of pretreatment samples from 11 of the patients revealed that all had been seropositive at presentation for auto-antibodies against the liver membrane lipoprotein preparation known as liver-specific membrane lipoprotein (LSP) and/or against the hepatic asialoglycoprotein receptor (ASGP R), titres of which subsequently fluctuated in direct relation to response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103406 TI - Correlation of hepatitis B surface antigen clearance with the route of hepatitis B virus infection. AB - We studied 563 consecutive adults with acute hepatitis B hospitalized from May 1981 to May 1983 and their habitual heterosexual partners. Radio-immunoassays for the detection of serological markers of hepatitis A virus (HAV) and hepatitis B virus (HBV) and enzyme-immunoassay for the detection of IgM antibody to hepatitis B core antigen (IgM anti-HBc) were used. Of the 563 patients, 503 (89.7%) were hepatitis B surface antigen (HBsAg) positive and 60 (10.7%) were HBsAg negative on admission. Absence of HBsAg on admission was observed significantly more frequently in patients infected possibly by the heterosexual route than in the remaining patients (23.3% versus 6.6%; P less than 0.001). This finding was independent of sex. These data show that the route of HBV infection rather than the sex appears to have a more important role in the rapid clearance of HBsAg. PMID- 2103407 TI - Effect of genetic obesity and experimental diabetes on hepatic microsomal mixed function oxidase activities. AB - In male rats, genetic obesity and experimental diabetes are associated with altered activities of several of the hepatic microsomal P-450 isozymes concerned with steroid and xenobiotic oxidation. The present study examined the roles of insulin and ketonaemia in effecting these changes. In obese male Zucker rats, androstenedione 6 beta-, 16 alpha- and 16 beta-hydroxylase activities (mediated by P450PCN-E, P-450UT-A and P450PB-B, respectively) were significantly decreased to 21%, 20% and 43% of lean control. Obesity was also associated with a significant decrease in the activities of N-nitrosodimethylamine demethylase (P 450j) and aniline p-hydroxylase to about 70%. A similar decrease in total microsomal P-450 was also observed. Androstenedione 7 alpha-hydroxylase activity (mediated by P-450UT-F) was unchanged in these animals. In streptozotocin-induced diabetic male Wistar rats, androstenedione 7 alpha- and 16 beta-hydroxylase activities were significantly elevated to 230% and 270% of control, respectively. Significant increases in the rates of N-nitrosodimethylamine demethylase and aniline p-hydroxylase were also noted in diabetic rat liver. In contrast, the activity of P-450UT-A was reduced to 30% of control and P-450PCN-E-specific 6 beta-hydroxylation was unchanged. Control of the diabetic state with insulin treatment reversed all the changes in P-450-mediated activities. Significant correlations were found between serum concentrations of insulin and catalytic activities of P-450PB-B (rho = -0.46), P-450UT-F (rho = -0.65) and P-450j (rho = 0.71). Positive correlations of the same magnitude were also found between these mixed function oxidase activities and beta-hydroxybutyrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103408 TI - Causative agents of acute diarrhoea in the first 3 years of life: hospital-based study. AB - During the 2 years of the study, 402 patients and an equal number of age- and sex matched controls were investigated for the presence of diarrhoeal pathogens. Pathogenic organisms were recovered from 277 (68.9%) patients and 97 (24.1%) controls. In the patient group, possible bacterial pathogens were found in 210 (52.2%) cases. Enteropathogenic Escherichia coli (EPEC) was the most frequently found potential pathogen, being recovered in 132 cases (32.8%) with serotypes 026, 086, 0111 and 0124 being the most frequently identified. Other bacterial pathogens identified were enterotoxigenic E. coli (ETEC) 57 (14.2%), Shigella 13 (3.2%) and Salmonella eight (2%). Rotavirus was identified in 33 (8.2%) cases. Mixed bacterial and viral infections were also seen in 26 (6.5%) cases. In the control group, enteric pathogens were recovered from 97 (24.1%) specimens. The most common bacterial pathogen found in this group was again EPEC (40, 9.9%), with serogroups 018, 044, 0111 and 0126 being the most frequent. Giardia lamblia and Entamoeba histolytica were found in 31 (7.7%) and 10 (2.5%) controls, respectively. Rotavirus was found in 16 (4%) controls. The results of both centres where the study was performed (Karachi and Rawalpindi) were compared. PMID- 2103409 TI - Serum pepsinogen I levels in patients with non-ulcer dyspepsia. AB - In order to understand whether the serum pepsinogen I (PGI) levels of non-ulcer dyspepsia (NUD) patients differed from those of healthy controls and which kinds of factors might influence these levels of the former, serum PGI levels were determined by radio-immunoassay in 120 healthy controls and 361 NUD patients. The mean serum PGI level was significantly lower in NUD patients than in the controls (75.8 +/- 38.2 ng/mL versus 95.9 +/- 39.3 ng/mL; P less than 0.0001); in NUD patients, it was significantly higher in males than in females (79.6 +/- 40.4 ng/mL versus 63.2 +/- 26.4 ng/mL; P less than 0.001). However, corrected serum PGI levels according to the lean body mass disclosed no sex difference. Nevertheless, there was a weak correlation between the ages of patients and serum PGI levels (r = 0.403). The serum PGI levels in blood groups A, B, AB and O did not differ significantly. Smoking might be a decisive factor, for the mean serum PGI level was significantly higher among the smokers than among the non-smokers (86.7 +/- 44.6 ng/mL versus 70.6 +/- 33.7 ng/mL; P less than 0.001). It is concluded that the mean serum PGI level of NUD patients, while affected by sex, age, smoker status and the body size, is lower than that of the healthy controls. Without endoscopy, assay of serum PGI level has no place in the diagnosis of dyspepsia because of the wide overlapping of serum PGI levels between NUD patients and patients with other common gastric lesions. PMID- 2103410 TI - Campylobacter pylori infection: experience in a multiracial population. AB - Over a 15-month period, 399 patients with dyspepsia were investigated for the presence of Campylobacter pylori infection. Half of the patients (50.6%) had Campylobacter organisms in the antrum of the stomach. C. pylori was found in 96.1% of patients with histological changes of chronic active gastritis in the antrum. Of patients with duodenal and gastric ulcers, 87.8% and 87.5%, respectively, had Campylobacter organisms, as did 39.3% of patients with non ulcer dyspepsia. C. pylori infection was most commonly found in Chinese and Indians. Although the prevalence of infection appeared to increase with age, there was an equal distribution amongst the sexes. PMID- 2103411 TI - In vivo cell kinetics studies of the duodenum during and after healing of cysteamine-induced duodenal ulcer in rats using bromodeoxyuridine incorporation. AB - The present study investigated the defect of duodenal defence responsible for the tendency of recurrence of duodenal ulcer. Male Wistar rats were treated with cysteamine-HCl subcutaneously to induce duodenal ulcer, and bromodeoxyuridine (BrdU) was given intraperitoneally 1 h before laparotomy. Serial tissue sections and immunocytochemical staining of BrdU were done to study the cell kinetics during and after healing. Deep ulcers developed in the proximal part of the duodenum 24 h after cysteamine injection, and the ulcer was replaced by scar tissue 1 week later. BrdU-labelling index of normal duodenal mucosa in control rats was 30-34%. On the peripheral part of the regenerative mucosa, BrdU labelling index increased from 1.5% to 26-27%, 1-4 weeks after injection and remained at this level thereafter. On the central part, except the most central area, the labelling index remained at 0% until 3 weeks, and was 15% 6 weeks after cysteamine treatment. It never achieved the level seen in control normal mucosa. The labelling rate of fibrous cells in scar tissue decreased from 28% to nearly 0% 1-4 weeks after the injection. It is concluded that both the ulcer scar and the regenerative mucosa do not achieve a mature state in the initial scarred stage; they need more time to reach a relatively mature condition. Moreover, the regenerative mucosa will be the weak, easily damaged part of the duodenum. PMID- 2103412 TI - Hepatic function and liver resection. PMID- 2103413 TI - Rhythms in morphology and function of hepatocytes. AB - In standard textbooks of histology, hepatocyte structure is described as being, for the most part, static. However, more than 50 years ago, it was reported that the glycogen content of rabbit hepatocytes varies significantly over 24 h. Since then, numerous investigators have confirmed this phenomenon in a variety of animals by use of morphological, histochemical and biochemical techniques, and it has been shown that the variation in glycogen content of hepatocytes corresponds with variations in enzymes related to glycogen metabolism. Moreover, there are also variations in most subcellular organelles and in many other proteins over 24 h. It is clear that circadian rhythms need to be taken into account in studies of morphology and function of hepatocytes. PMID- 2103414 TI - Hepatic toxicity of vitamin A and synthetic retinoids. AB - Vitamin A and synthetic retinoids have recently been used increasingly in a variety of health related concerns. Hepatic toxicity is an uncommon but serious side-effect of several Vitamin A derivatives which may lead to cirrhosis. This review will focus on the clinical and pathologic findings of hepatic involvement in chronic hypervitaminosis A and on the evidence concerning the potential hepatotoxicity of currently available synthetic retinoids. PMID- 2103415 TI - Auto-immune chronic active hepatitis: a specific entity? The negative argument. PMID- 2103416 TI - Auto-immune (lupoid) hepatitis: an entity in the spectrum of chronic active liver disease. AB - The concept of auto-immune hepatitis as a disease entity evolved from the descriptions of 'chronic active hepatitis' (CAH) in the 1950s. Several types of CAH are distinguished by disease-specific features. The distinctive (but not exclusive) markers for auto-immune CAH include: a negative test for HBsAg; female; Northern European ethnic background; multisystem disease expression; histological CAH with large areas of periportal piecemeal necrosis and plasmacytosis; pronounced hypergammaglobulinaemia; serum auto-antibodies the HLA B8-DR3 phenotype; responsiveness to corticosteroid therapy; and rarity of supervening hepatocellular carcinoma. Much weight is attached to the serological marker auto-antibodies to nuclear or smooth muscle (actin) antigens (ANA, SMA). However, these auto-antibodies do not have an absolute association with auto immune CAH: the serological reactions are not yet standardized; titres decrease with remission of disease; and other auto-antibodies mark variant forms of auto immune hepatitis. A more confident acceptance of auto-immune hepatitis as an entity requires detection of a liver-specific antigen, a valid experimental disease model in animals, and a better understanding of immune-mediated damage to liver cells. PMID- 2103417 TI - Classification of auto-immune chronic active hepatitis. PMID- 2103418 TI - The normal structure of gastrointestinal innervation. PMID- 2103419 TI - Growth factors and the gut. PMID- 2103420 TI - Liver transplantation: results, advances and problems. PMID- 2103421 TI - Anorectal and pelvic floor disorders: putting physiology into practice. AB - The pathophysiology of the pelvic floor syndromes is complex and confusing. Childbirth is the only aetiological agent to have been clearly identified, but its role is not universal. Learned or psychogenic pelvic floor incoordination is likely to play a part. The conditions are so intertwined that an increasingly comprehensive battery of tests has become necessary to try to unravel the component disorders; anorectal physiology testing has therefore assumed an important position in the evaluation of these patients. It is only by careful application of physiological studies in clinical practice that further advances can be made. The investigations currently available can contribute significantly to determining the optimum management of these difficult patients. Surgical indications continue to be refined. The results of careful clinical and laboratory follow-up studies have led to changes in practice. The pelvic floor syndromes have only recently been defined; there is still much work to be done. PMID- 2103422 TI - Management of colorectal polyps: is all the effort worthwhile? PMID- 2103423 TI - Endoscopic treatment of bleeding peptic ulcer. AB - Several endoscopic modalities have the potential of controlling major, life threatening ulcer bleeding. Although none of the modalities has emerged to be more efficacious than the other, current evidence favours thermal methods and injection therapy. When successful, the endoscopic methods are equally safe (associated with a risk of perforation less than 2%), although a rebleeding rate of 10-30% is of concern. Endoscopic therapy is in general operator-dependent, and the experience of a team is probably more important than the choice of equipment. Selection of patients for endoscopic therapy should be based on the identification of high-risk patients who tolerate rebleeding or surgery poorly, and high-risk lesions likely to rebleed. Endoscopic therapy for ulcer bleeding is simply a new way of applying surgery. Realizing this, it is difficult to understand why therapeutic endoscopy for bleeding ulcer has not yet been widely adopted by surgeons. PMID- 2103424 TI - Infection, malnutrition and growth. PMID- 2103425 TI - Revolution in liver surgery. PMID- 2103426 TI - DNA methylation in the Alcohol dehydrogenase-1 gene of maize. AB - Using a battery of methylation-sensitive restriction enzymes, cytosine methylation at 23 sites in a 7.6 kb region surrounding the Alcohol dehydrogenase 1 (Adh1) gene was measured in DNA prepared from immature maize cobs. Both the 5' upstream region and the entire coding region were hypomethylated in the two alleles examined. Methylation in Adh1 is independent of changes in Mutator transposable element methylation. The role of DNA methylation in Adh1 gene regulation is discussed. PMID- 2103427 TI - Sulfonamide resistance gene for plant transformation. AB - The sulfonamide resistance gene from plasmid R46 encodes for a mutated dihydropteroate synthase insensitive to inhibition by sulfonamides. Its coding sequence was fused to the pea ribulose bisphosphate carboxylase/oxygenase transit peptide sequence. Incubation of isolated chloroplasts with the fusion protein synthesised in vitro, showed that the bacterial enzyme was transported to the chloroplast stroma and processed into a mature form. Expression of the gene fusion in transgenic plants resulted in a high level of resistance to sulfonamides. Direct selection of transformed shoots on leaf explants was efficient using sulfonamides as sole selective agents. Transformed shoots rooted normally on sulfonamides at concentrations toxic for untransformed ones. Sulfonamide resistance was transmitted to the progeny of transformed plants as a single Mendelian dominant character. These results demonstrate that this chimeric gene can be used as an efficient and versatile selectable marker for plant transformation. PMID- 2103428 TI - Transcriptional activation of 2 classes of genes during the hypersensitive reaction of tobacco leaves infiltrated with an incompatible isolate of the phytopathogenic bacterium Pseudomonas solanacearum. AB - Fourteen cDNA clones whose corresponding mRNAs accumulate during the hypersensitive reaction (HR) of tobacco leaves infiltrated with an incompatible strain of the bacterial pathogen Pseudomonas solanacearum have been subdivided by sequence homologies into 6 families. Studies on the accumulation of the mRNAs encoded by these genes in compatible and incompatible plant-bacterial interactions have been carried out and indicate that the 6 cDNA clones can be subdivided into 2 groups. In one group corresponding to 3 cDNA clones, the maximal level of mRNA accumulation is similar in both types of interaction, whereas in the other group, maximal mRNA accumulation in leaves undergoing an HR is 3- to 7-fold higher than in leaves infiltrated with the compatible strain. Within each group, the timing and kinetics of accumulation of the corresponding mRNAs differ for each individual cDNA clone. Run-on experiments indicate that transcriptional activation of these genes plays a major role in the control of their expression. Genomic hybridizations have been performed and indicate that the mRNAs corresponding to the cDNA clones are encoded by multigene families (6 to 20 genes). PMID- 2103429 TI - A repetitive sequence from Diplotaxis erucoides is highly homologous to that of Brassica campestris and B. oleracea. PMID- 2103430 TI - Sequence of two tomato nuclear genes encoding chlorophyll a/b-binding proteins of CP24, a PSII antenna component. PMID- 2103431 TI - Nucleotide sequence of a ripening-related cDNA from avocado fruit. PMID- 2103432 TI - Rapid and efficient detection of genetic polymorphism in wheat through amplification by polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to amplify genomic DNA of several wheat genotypes. The oligonucleotides used as primers were the terminal sequences of a gamma-gliadin gene. The electrophoretic analysis of the PCR products showed specific bands which revealed both inter- and intra-specific genetic polymorphism among the examined genotypes. The technique is proposed as a very simple and efficient alternative to RFLP markers. PMID- 2103433 TI - Nopaline synthase gene is expressed in Escherichia coli and in cucumber cells under a hybrid promoter. AB - Fusion of the nopaline synthase gene (nos) to the Escherichia coli trp promoter gave rise to a hybrid promoter (tros). Under control of this hybrid element, synthesis of nopaline was observed in E. coli as well as in cucumber cells transformed with the described vector. PMID- 2103434 TI - Molecular cloning of a lupin-specific gene from a cDNA library of suspension cultured cells of Lupinus polyphyllus. PMID- 2103435 TI - The figwort mosaic virus gene VI promoter region contains a sequence highly homologous to the octopine synthase (ocs) enhancer element. PMID- 2103436 TI - Nucleotide sequence of a spinach nitrate reductase cDNA. PMID- 2103437 TI - Variation in the nucleotide sequence of a prolamin gene family in wild rice. AB - Variation in the DNA sequence of the 10 kDa prolamin gene family within the wild rice species Oryza rufipogon was probed using the direct sequencing of PCR amplified genes. A comparison of the nucleotide and deduced amino-acid sequences of eight Asian strains of O. rufipogon and one strain of the related African species O. longistaminata is presented. PMID- 2103438 TI - Complete sequence of a cDNA of alpha subunit of soybean beta-conglycinin. PMID- 2103439 TI - Genomic sequence of a Brassica S locus-related gene. PMID- 2103440 TI - Over-expressing a yeast ornithine decarboxylase gene in transgenic roots of Nicotiana rustica can lead to enhanced nicotine accumulation. AB - Transformed root cultures of Nicotiana rustica have been generated in which the gene from the yeast Saccharomyces cerevisiae coding for ornithine decarboxylase has been integrated. The gene, driven by the powerful CaMV35S promoter with an upstream duplicated enhancer sequence, shows constitutive expression throughout the growth cycle of some lines, as demonstrated by the analysis of mRNA and enzyme activity. The presence of the yeast gene and enhanced ornithine decarboxylase activity is associated with an enhanced capacity of cultures to accumulate both putrescine and the putrescine-derived alkaloid, nicotine. Even, however, with the very powerful promoter used in this work the magnitude of the changes seen is typically only in the order of 2-fold, suggesting that regulatory factors exist which limit the potential increase in metabolic flux caused by these manipulations. Nevertheless, it is demonstrated that flux through a pathway to a plant secondary product can be elevated by means of genetic manipulation. PMID- 2103441 TI - Organ-specific modulation of gene expression in transgenic plants using antisense RNA. AB - We have shown leaf-specific inhibition GUS gene expression in transgenic Nicotiana plants using an antisense RNA with a 41-base homology spanning the translation start codon of the gene. GUS was expressed from the nominally constitutive 35S promoter and the antisense RNA was expressed from the light regulated ca/b promoter of Arabidopsis thaliana. A range of GUS inhibition from 0 to 100% was obtained by screening a small population of transgenic plants and the specific levels of inhibition observed were stably inherited in two generations. An antiGUS 'gene' dosage effect was observed in plants which were homozygous for antiGUS. RNA detection results suggest that duplex formation with the 41 base pair antiGUS RNA destabilized the GUS mRNA and that an excess of antisense RNA was not required. Our results demonstrate the potential of antisense RNA as a strategy for obtaining plant mutants, especially 'down mutations' in essential genes where only a short 5' sequence of the mRNA is required. They also suggest that the 'position effect' on gene expression could be used in conjunction with an antisense RNA strategy to provide a versatile approach for crop improvement. PMID- 2103442 TI - Differential expression of individual genes encoding the small subunit of ribulose-1,5-bisphosphate carboxylase in Lemna gibba. AB - The gene family encoding the small subunit (SSU) of ribulose-1,5-bisphosphate carboxylase/oxygenase in the monocot Lemna gibba contains approximately twelve members. We have isolated six of these genes from a genomic library, and sequenced five of the coding regions. The transit peptide nucleotide sequences are conserved, but less highly than the mature polypeptide coding sequence. The mature polypeptide amino acid sequences are identical to each other and to the sequence deduced from a cDNA clone derived from a seventh gene. Each of the five fully characterized genomic sequences contains a single intron in precisely the same position as the second intron of several dicots. The intron sequences differ in length and are less conserved than the coding sequences. The 3'-untranslated regions of the different genes have been sequenced and used to prepare gene specific probes. These probes have been used to study the expression levels of individual rbcS sequences. Expression of six of the seven genes can be detected in total RNA isolated from plants grown in continuous light. The levels of RNA encoded by each expressed gene are regulated by the action of phytochrome, but there is variability in the amount of expression of each RNA. PMID- 2103443 TI - Stored mRNA in cotyledons of Vigna unguiculata seeds: nucleotide sequence of cloned cDNA for a stored mRNA and induction of its synthesis by precocious germination. AB - By differential hybridization screening, we previously selected a class of cDNA clones from a lambda gt10 cDNA library that was constructed from the total poly(A)+ RNA of mature cowpea cotyledons (Plant Cell Physiol 31: 39-44, 1990). pSAS10, a clone of this class, hybridized with a cDNA probe complementary to poly(A)+ RNA from cotyledons collected 1 day after the onset of imbibition (DAI), but not with the cDNA probe from cotyledons at developmental stage II (13 to 15 days after flowering, DAF). pSAS10 mRNA was detectable only in cotyledons at developmental stage III (17 to 19 DAF) or later, and its level began to decline when seeds germinated. We have suggested that pSAS10 mRNA is likely to belong to the class of 'stored' mRNA or the mRNA that is formed at the late stage of seed maturation, is conserved in quiescent seeds and becomes functional at the early stage of germination. We determined the nucleotide sequence of pSAS10 cDNA consisting of 459 bp and an approximately 36 bp poly(A) tract, and deduced the amino acid sequence of its product, a 10-kDa cysteine-rich polypeptide. Synthesis of pSAS10 mRNA was induced just before germination began, not only in mature seeds but also in immature seeds even at stages I (9 to 11 DAF) and II (13 to 15 DAF) if they were placed under conditions suitable for germination. PMID- 2103444 TI - Analysis of leaky viral translation termination codons in vivo by transient expression of improved beta-glucuronidase vectors. AB - Plant RNA viruses commonly exploit leaky translation termination signals in order to express internal protein coding regions. As a first step to elucidate the mechanism(s) by which ribosomes bypass leaky stop codons in vivo, we have devised a system in which readthrough is coupled to the transient expression of beta glucuronidase (GUS) in tobacco protoplasts. GUS vectors that contain the stop codons and surrounding nucleotides from the readthrough regions of several different RNA viruses were constructed and the plasmids were tested for the ability to direct transient GUS expression. These studies indicated that ribosomes bypass the leaky termination sites at efficiencies ranging from essentially 0 to ca. 5% depending upon the viral sequence. The results suggest that the efficiency of readthrough is determined by the sequence surrounding the stop codon. We describe improved GUS expression vectors and optimized transfection conditions which made it possible to assay low-level translational events. PMID- 2103445 TI - The maize zein gene zE19 contains two distinct promoters which are independently activated in endosperm and anthers of transgenic Petunia plants. AB - The activity, tissue specificity and temporal expression of the tandem promoter region preceding a maize zein gene (zE19, encoding a 19 kDa zein protein) were tested in transgenic Petunia plants. To simplify the analysis, the tandem promoter as well as each of the two separate promoter regions were fused to the beta-glucuronidase (GUS) reporter gene. All of the three constructs directed the synthesis of GUS in the endosperm of transformed seeds indicating that both separate promoters are independently activated and show the same tissue and cell type specificity observed for zein genes in maize. The kinetics of accumulation and the localization of GUS activity are not coordinated with those of Petunia endogenous seed storage proteins during the development of transformed seeds. Unexpectedly, we detected high levels of GUS activity in anthers of transformed Petunia plants for all three constructs. This appears to reflect the expression pattern of zein genes in maize, since we detect zein transcripts in anthers. Finally, we discuss the possible origin and function of the tandem promoter arrangement on the basis of these data. PMID- 2103446 TI - Promoter analysis of the chalcone synthase (chsA) gene of Petunia hybrida: a 67 bp promoter region directs flower-specific expression. AB - In order to scan the 5' flanking region of the chalcone synthase (chs A) gene for regulatory sequences involved in directing flower-specific and UV-inducible expression, a chimaeric gene was constructed containing the chs A promoter of Petunia hybrida (V30), the chloramphenicol acetyl transferase (cat) structural sequence as a reporter gene and the chs A terminator region of Petunia hybrida (V30). This chimaeric gene and 5' end deletions thereof were introduced into Petunia plants with the help of Ti plasmid-derived plant vectors and CAT activity was measured. A 220 bp chs A promoter fragment contains cis-acting elements conferring flower-specific and UV-inducible expression. A promoter fragment from 67 to +1, although at a low level, was still able to direct flower-specific expression but could not drive UV-inducible expression in transgenic Petunia seedlings. Molecular analysis of binding of flower nuclear proteins to chs A promoter fragments by gel retardation assays showed strong specific binding to the sequences from -142 to +81. Promoter sequence comparison of chs genes from other plant species, combined with the deletion analysis and gel retardation assays, strongly suggests the involvement of the TACPyAT repeats (-59 and -52) in the regulation of organ-specificity of the chs A gene in Petunia hybrida. We also describe an in vitro organ-specific transient expression system, in which flower or purple callus protoplasts are used, that enables us to pre-screen organ specific expression of a chimaeric reporter gene. PMID- 2103447 TI - Analysis of the genes encoding the largest subunit of RNA polymerase II in Arabidopsis and soybean. AB - We have cloned and sequenced the gene encoding the largest subunit of RNA polymerase II (RPB1) from Arabidopsis thaliana and partially sequenced genes from soybean (Glycine max). We have also determined the nucleotide sequence for a number of cDNA clones which encode the carboxyl terminal domains (CTDs) of RNA polymerase II from both soybean and Arabidopsis. The Arabidopsis RPB1 gene encodes a polypeptide of approximately 205 kDa, consists of 12 exons, and encompasses more than 8 kb. Predicted amino acid sequence shows eight regions of similarity with the largest subunit of other prokaryotic and eukaryotic RNA polymerases, as well as a highly conserved CTD unique to RNA polymerase II. The CTDs in plants, like those in most other eukaryotes, consist of tandem heptapeptide repeats with the consensus amino acid sequence PTSPSYS. The portion of RPB1 which encodes the CTD in plants differs from that of RPB1 of animals and lower eukaryotes. All the plant genes examined contain 2-3 introns within the CTD encoding regions, and at least two plant genes contain an alternatively spliced intron in the 3' untranslated region. Several clustered amino acid substitutions in the CTD are conserved in the two plant species examined, but are not found in other eukaryotes. RPB1 is encoded by a multigene family in soybean, but a single gene encodes this subunit in Arabidopsis and most other eukaryotes. PMID- 2103448 TI - Agrobacterium-mediated plant transformation by novel mini-T vectors in conjunction with a high-copy vir region helper plasmid. AB - A new binary vector system for Agrobacterium-mediated plant transformation was developed. A set of four mini-T vectors comprised of T-DNA border sequences from nopaline-type Ti-plasmid pTiC58 flanking a chimaeric hygromycin-resistance gene for selection of transformants and up to eight unique restriction sites for cloning foreign DNA was constructed on a broad-host replicon containing the oriV of plasmid pSa. In two of the constructs these multiple cloning sites are flanked by a strong promoter to activate transcription of inserted DNA in planta. High efficiency transformation was prompted by a high-copy, stable virulence helper plasmid pUCD2614, which contains a cloned virulence region of pTiC58 and tandem copies of the par locus of plasmid pTAR. Southern blot hybridization and genetic analyses of the progeny of transformed plants showed that the hygromycin resistance gene was stably inherited. PMID- 2103449 TI - Characterization of the rice (Oryza sativa) actin gene family. AB - Four rice (Oryza sativa) genomic actin genes have been characterized. The rice actin genes show a conservation of intron number and position that is characteristic of plant actins. Sequence comparisons revealed that the plant actins generally have a high degree of inter- and intraspecific sequence heterogeneity. However, one rice actin gene has a much higher degree of nucleotide sequence identity to a previously isolated actin sequence from Arabidopsis thaliana than to any other plant actin gene. This leads us to suggest that the two sequences may represent functionally homologous genes which arose from an ancient actin gene lineage that was separated by the divergence of the dicot and monocot plants. Genomic DNA blot analysis showed that the rice actin gene family contains at least eight unique members. RNA hybridization analysis revealed that individual rice actin genes can display different patterns of transcript accumulation. The observed differences in sequence and transcript accumulation patterns suggest that the individual rice actin genes may differ in their transcriptional regulation and/or cellular function. PMID- 2103450 TI - Evidence for a composite phylogenetic origin of the plastid genome of the brown alga Pylaiella littoralis (L.) Kjellm. AB - The nucleotide sequence and the 5' flanking region of the rbcL gene coding for the large subunit of ribulose bisphosphate-1,5-carboxylase/oxygenase of Pylaiella littoralis, a brown alga, has been determined and the deduced amino-acid sequence has been compared to those of various photosynthetic and chemoautotrophic Eubacteria, of a red alga and of green plastids (Euglena gracilis, green algae and higher plants). Unlike the rbcL genes of green plastids which are more closely related to those of cyanobacteria, the P. littoralis rbcL gene is more closely related to that of a beta-purple bacterium, as was found for the rbcS gene of another chromophytic alga [Boczar et al., Proc Natl Acad Sci USA 86: 4996 4999, 1989]. Matrix data of homology between the rbcL gene of P. littoralis and the same gene of other organisms are presented. Based on our previous report, the gene coding for the 16S rRNA from P. littoralis is closely related to that of E. gracilis (Markowicz et al., Curr Genet 14: 599-608, 1988). We suggest that the large plastid DNA molecule of P. littoralis is a phylogenetically composite genome which probably resulted from mixed endosymbiosis events, or from a horizontal transfer of DNA. PMID- 2103451 TI - Expression of a stilbene synthase gene in Nicotiana tabacum results in synthesis of the phytoalexin resveratrol. AB - A gene from groundnut (Arachis hypogaea) coding for stilbene synthase was transferred together with a chimaeric kanamycin resistance gene. It was found to be rapidly expressed after induction with UV light and elicitor in tobacco cells (Nicotiana tabacum). Comparative studies of stilbene synthase mRNA synthesis in groundnut and transgenic tobacco suspension cultures revealed the same kinetics of gene expression. Stilbene synthase specific mRNA was detectable 30 minutes after elicitor induction and 10 minutes after UV irradiation. The maximum of mRNA accumulation was between 2 and 8 hours post induction. 24 hours after induction stilbene synthase mRNA accumulation ceased. Furthermore, in transgenic tobacco plants, the gene was found to be inducible in sterile roots, stems and leaves. Stilbene synthase was demonstrated in crude protein extracts from transgenic tobacco cell cultures using specific antibodies. Resveratrol, the product of stilbene synthase, was identified by HPLC and antisera raised against resveratrol. PMID- 2103452 TI - Sequence analysis of three tRNA(Phe) nuclear genes and a mutated gene, and one gene for tRNA(Ala) from Arabidopsis thaliana. AB - Three genes and one mutant gene for tRNA(Phe) (GAA) and one gene for tRNA(Ala) (UGC) were isolated from a whole-cell DNA library of Arabidopsis thaliana. All three tRNA(Phe) genes are identical in their nucleotide sequence, but differ in their 5' and 3' flanking regions. The mutant tRNA(Phe) (GAA) gene differs from the other three genes by one nucleotide change from highly conserved G to C at the 57th nucleotide position. The primary structure of the first tRNA(Ala) gene was also determined in this experiment. PMID- 2103453 TI - An open reading frame encoding a putative haem-binding polypeptide is cotranscribed with the pea chloroplast gene for apocytochrome f. AB - The nucleotide sequence of a 1 kbp region of pea chloroplast DNA upstream from the gene petA encoding apocytochrome f has been determined. An open reading frame of 231 codons (ORF231) encoding a putative membrane-spanning polypeptide is separated by 205 bp from the coding region of petA. The open reading frame is homologous to open reading frames located in a similar position with respect to petA in chloroplast DNA from Marchantia polymorpha, tobacco, rice, wheat and Vicia faba. The sequence around a conserved histidine residue in a putative membrane-spanning region of the polypeptide resembles sequences present in cytochrome b from chromaffin granules and neutrophil membranes, suggesting that the open reading frame may encode a haem-binding polypeptide, possibly a b-type cytochrome. Northern hybridisation analysis indicates the presence in pea chloroplasts of a complex pattern of transcripts containing ORF231. Large transcripts of 5.5 kb, 4.3 kb, 3.4 kb and 2.7 kb encode both ORF231 and apocytochrome f, indicating that ORF231 and petA are co-transcribed. PMID- 2103454 TI - The mitochondrial apocytochrome b gene from Chlamydomonas reinhardtii. PMID- 2103455 TI - Isolation and nucleotide sequence of cDNA clone encoding nodule-specific (hydroxy)proline-rich protein LENOD2 from yellow lupin. PMID- 2103456 TI - Nucleotide sequence of a tRNA pseudogene from wheat mitochondrial. PMID- 2103457 TI - Nucleotide sequence of the hydrogenase structural genes from Rhizobium leguminosarum. PMID- 2103458 TI - Novel and useful properties of a chimeric plant promoter combining CaMV 35S and MAS elements. AB - The CaMV 35S and Ti plasmid mannopine synthetase (mas) promoters are commonly used by plant genetic engineers. To combine their useful properties, we constructed hybrid promoters incorporating elements from both. These promoters were spliced to the beta-glucuronidase reporter gene and introduced into tobacco and tomato plants by Agrobacterium cocultivation. T1 and T2 transgenic plant populations transformed with different constructs were assayed for the marker enzyme. Comparisons were made based on the range of expression levels found for each promoter construct. We found that a hybrid promoter incorporating the mas region from +65 to -301 and the 35S enhancer region from -90 to -941 had new and interesting properties. This promoter, called Mac, expressed gus at a level three to five times that expressed by a double 35S promoter in the leaves, and 10 to 15 times in hypocotyls and roots. The Mac promoter, however, showed only marginal wound inducibility. Five- to seven-fold wound induction required the presence of the region from -301 to -613 of mas. Reiteration of the 35S enhancer region, from -90 to -430, behind the 35S TATA box region or the mas +65 to -301 region had a smaller effect on expression, ranging from equal to twice the level of the single enhancer control. PMID- 2103459 TI - A low molecular weight DNA polymerase from wheat embryos. AB - The study of plant DNA polymerases lags far behind that concerning their animal or yeast counterpart. In this work we describe the first extensive purification to apparent homogeneity, as well as a detailed biochemical and immunological characterization, of a low molecular weight DNA polymerase (DNA polymerase CI) purified from wheat embryos. The monomeric enzyme is a basic protein having a molecular weight of 52 kDa. Polyclonal antibodies raised in rabbits against DNA polymerase CI did not inhibit animal DNA polymerases alpha and beta or wheat DNA polymerase A, whereas wheat DNA polymerases CII and B were much less affected than the CI enzyme. Several properties of enzyme CI were studied. Some known inhibitors of DNA polymerase activity including aphidicolin, phosphonoacetic acid and heparin, did not affect DNA polymerase CI while the activity of this enzyme was strongly inhibited by ddTTP and N-ethylmaleimide. The polyamine spermine decreased markedly the enzyme activity, while spermidine produced a strong stimulation at the same concentrations that spermine inhibited the enzyme. The best template for this enzyme is poly dA-oligo dT, although polymerase CI can recognize significantly some synthetic polyribonucleotide templates (poly rC oligo dG, poly rA-oligo dT) but only at a given protein/template primer ratio. The enzyme is blocked at the amino terminus, thus preventing the automatic sequencing of the protein. The amino acid analysis showed a striking similarity with the animal low molecular weight DNA polymerase beta. The latter observation, as well as the effect of inhibitors (except N-ethylmaleimide which does not inhibit the animal polymerase) indicate that the DNA polymerase described in this work is a plant DNA polymerase very similar to the low molecular weight animal DNA polymerase beta, an enzyme believed to be involved in nuclear DNA repair. PMID- 2103460 TI - Structure and expression of a light-inducible shoot-specific rice gene. AB - By differential screening of a cDNA library of two-week-old rice seedlings cDNA clones were obtained, corresponding to shoot-specific mRNAs. By sequence analysis two of these clones were found to be rbcS cDNA clones. The mRNA corresponding to a third cDNA clone (COS5) displayed an expression pattern similar to the expression pattern of rbcS genes. The mRNA (800 bases) was light-inducible and encoded by a single-copy gene. The genomic clone (GOS5) was isolated and the intron/exon structure was determined by comparing the nucleotide sequences of the mRNA and the genomic clone. The gene contains two introns. Transcription start sites were determined by S1-nuclease mapping and primer extension. The start site obtained by both methods is located 87 bp upstream of the translation start site and 23 bp downstream of TATA box-like sequence. In the 5' non-coding region motifs can be found that are homologous to sequences in promoters that are light- or UV-inducible or confer leaf-specific expression. The open reading frame present in GOS5 codes for a protein (15 kDa) that contains a putative chloroplast transit peptide and does not show any significant homology to protein sequences in the NBRF protein database. PMID- 2103461 TI - Restoration of shooty morphology of a nontumorous mutant of Nicotiana glauca x N. langsdorffii by cytokinin and the isopentenyltransferase gene. AB - The shooty morphology of a nontumorous amphidiploid mutant of Nicotiana glauca Grah. x N. langsdorffii Weinm. was restored by cytokinins, whether exogenously applied or endogenously produced by transformation of the mutant with a transfer DNA (T-DNA) cytokinin-biosynthesis gene (isopentenyltransferase; ipt). Auxins alone did not confer this effect. Similar transformation was not achieved for the parental species. In the case of transformation with the ipt gene, selection of the transformed tissues was based on its hormone-independent growth in the presence of the antibiotic kanamycin. Transformed tissues exhibited a shooty morphology, indistinguishable from that of wildtype genetic tumors N. glauca x N. langsdorffii. This altered phenotype was caused by the presence and constitutive expression of the ipt gene. The insertion and expression of this gene in transformed tissues was confirmed by using the polymerase chain reaction (PCR) technique as well as conventional molecular hybridization analysis. Expression of the ipt gene led to an elevated level of cytokinin in the transformed mutant tissues. This evidence supports the notion that genetic tumors are caused, at least in part, by elevated levels of cytokinin in interspecific hybrids. PMID- 2103462 TI - Nomad DNA--a model for movement and duplication of DNA sequences in plant genomes. PMID- 2103463 TI - A ferredoxin-type iron-sulfur protein gene, frx B, is expressed in the chloroplasts of tobacco and spinach. AB - Previously, a ferredoxin-type iron-sulfur protein, frx B protein, was identified in a high-salt extract of the purified thylakoid membrane of Chlamydomonas reinhardtii, a unicellular green alga. Polyclonal antibody was raised against a synthetic pentadecameric peptide with an amino acid sequence corresponding to the highly conserved region of the putative frx B proteins of 3 land plants. In this report, protein(s) reacting strongly and specifically with this antibody was detected in the equivalent high-salt extract prepared from purified chloroplast of spinach and tobacco. One strong reaction polypeptide band from tobacco chloroplast was purified from SDS-polyacrylamide gel and subjected to endoproteinase lys C digestion. The resulting polypeptides were separated by reversed-phase chromatography. N-terminal sequencing of 3 purified polypeptides revealed that the protein is encoded by the 'frxB gene' identified from DNA sequence analysis. PMID- 2103464 TI - Length heterogeneity of the rRNA precursor in cucumber (Cucumis sativus). AB - The length homogeneous part of the intergenic spacer (IGS) of the 18S-25S ribosomal RNA genes of cucumber (Cucumis sativus) was characterized by sequencing 2389 bp preceding the 18S rRNA coding region of a 12.5 kbp repeat type. This part of the IGS is composed of repeated elements and shows a very complex structural organization. Most obvious is a 119 bp element which is repeated seven times. A single transcription initiation site (TIS) was detected by a 'T4 polymerase stop' experiment upstream of these repetitions giving rise to a 2013 bp 5' external transcribed spacer (ETS) for cucumber. Nuclease mapping showed several transcription termination sites (TTS): the first one is located 350 bp downstream of the 25S rRNA coding region, the others are found within the duplications of this region accounting for the length heterogeneity of cucumber rDNA. Therefore, the TTS is repeated two or three times in the IGS depending on the length of the respective repeat classes and the rRNA precursor is heterogeneous in length varying from approx. 8000 to 11000 nts. PMID- 2103465 TI - Transfer of hygromycin resistance into Brassica napus using total DNA of a transgenic B. nigra line. AB - The successful transfer of a marker gene (hpt gene) from Brassica nigra into B. napus via direct gene transfer was demonstrated. Total DNA was isolated from a hygromycin-resistant callus line, which contained three to five copies of the hpt gene. This line had been produced via direct gene transfer with the hygromycin resistance-conferring plasmid pGL2. The treatment of B. napus protoplasts with genomic DNA of B. nigra (HygR) resulted in relative transformation frequencies of 0.1-0.4%. Similar transformation rates were obtained in direct gene transfer experiments using B. napus protoplasts and plasmid pGL2. PMID- 2103466 TI - mRNAs newly synthesized by tobacco mesophyll protoplasts are wound-inducible. AB - We have used 2-dimensional (2D) non-equilibrium pH gradient gel electrophoresis (NEPHGE) of in vitro synthesized proteins and northern hybridization with labelled cDNAs coding for three pathogenesis related (P.R.) proteins, to analyze the shift in mRNA content induced by the isolation and culture of tobacco mesophyll protoplasts. The in vitro protein pattern of mRNAs from freshly isolated protoplasts is characterized by the absence of most leaf spots and the appearance of 19 new spots. After 6 hours of culture, the mRNAs coding for the P.R. proteins become detectable and after 12 hours the protoplasts contain an mRNA population almost typical of callus cells. The different steps involved in the isolation and culture of protoplasts were analysed. Cutting off the leaf and sterilization do not change the mRNA set. In contrast, the mechanical injury applied to the leaf in order to facilitate the penetration of the enzymatic mixture induces a modification of the mRNA content identical to that resulting from protoplast isolation. Wounding is the essential event inducing dedifferentiation. Varying the culture medium and conditions leads to only limited modifications of the mRNA pattern. These results are discussed on the basis of present knowledge of the reaction of the plant to wounding and we suggest that wound healing callus and in vitro callus correspond to the same differentiation state. PMID- 2103467 TI - Nucleotide sequence analysis of a cDNA clone encoding malate synthase of castor bean (Ricinus communis) reveals homology to DAL7, a gene involved in allantoin degradation in Saccharomyces cerevisiae. PMID- 2103468 TI - Sequence of the gene for the large subunit of ribulose 1,5-bisphosphate carboxylase from a gymnosperm, Douglas fir. PMID- 2103469 TI - A new strain of potato spindle tuber viroid (PSTVd-N) exhibits major sequence differences as compared to all other PSTVd strains sequenced so far. PMID- 2103470 TI - Cloning and sequencing of the Arabidopsis aldolase gene. PMID- 2103471 TI - Characterization of cDNA clones for a virus-inducible, glycine-rich protein from petunia. PMID- 2103472 TI - Extensive sequence similarity of the bean CAD4 (cinnamyl-alcohol dehydrogenase) to a maize malic enzyme. PMID- 2103473 TI - Evidence for a third structural class of beta-1,3-glucanase in tobacco. AB - Glucan endo-1,3-beta-glucosidases (beta-1,3-glucanases) have been implicated in several developmental processes and they may also play a direct role in the plant's defense against fungal pathogens. In an effort to characterize the glucanase gene family, complementary DNA clones encoding an acidic form of beta 1,3-glucanase have been isolated from tobacco. The cDNA was expressed in E. coli and shown to encode a beta-1,3-glucanase activity. The protein sequence encoded by the cDNA was found to match the partial protein sequence of PR-35, a previously characterized beta-1,3-glucanase. The protein encoded by the cDNA was purified from the extracellular fluid of TMV-infected tobacco leaves and found by immunological methods to correspond to glucanase PR-Q'. From a detailed analysis of the cDNA it is clear that this glucanase represents a third structural class of enzyme which differs substantially from both the basic, vacuolar glucanase and the acidic, extracellular forms (PR-2, PR-N and PR-O). It has previously been demonstrated that the basic form of beta-1,3-glucanase is synthesized as a pre pro-enzyme and upon maturation the 21 amino acid signal peptide and a 22 amino acid carboxy-terminal peptide are removed. This processing event has been proposed to be involved with the vacuolar localization of the enzyme. By comparing the deduced protein structure of PR-Q' to that of the basic form it is evident that this extracellular enzyme is missing the carboxy-terminal 22 amino acids. The role of a conserved phenylalanine-glycine dipeptide in the processing of glucanases and other pathogenesis-related proteins from tobacco is discussed. PMID- 2103474 TI - Optimization of delivery of foreign DNA into higher-plant chloroplasts. AB - We report here an efficient and highly reproducible delivery system, using an improved biolistic transformation device, that facilitates transient expression of beta-glucuronidase (GUS) in chloroplasts of cultured tobacco suspension cells. Cultured tobacco cells collected on filter papers were bombarded with tungsten particles coated with pUC118 or pBI101.3 (negative controls), pBI505 (positive nuclear control) or a chloroplast expression vector (pHD203-GUS), and were assayed for GUS activity. No GUS activity was detected in cells bombarded with pUC118 or pBI101.3. Cells bombarded with pBI505 showed high levels of expression with blue color being distributed evenly throughout the whole cytosol of the transformants. pHD203-GUS was expressed exclusively in chloroplasts. We base this conclusion on: i) the procaryotic nature of the promoter used in the chloroplast expression vector; ii) delayed GUS staining; iii) localization of blue color within subcellular compartments corresponding to plastids in both shape and size; and iv) confirmation of organelle-specific expression of pHD203-GUS using PEG mediated protoplast transformation. Chloroplast transformation efficiencies increased dramatically (about 200-fold) using an improved helium-driven biolistic device, as compared to the more commonly used gun powder charge-driven device. Using GUS as a reporter gene and the improved biolistic device, optimal bombardment conditions were established, consistently producing several hundred transient chloroplast transformants per Petri plate. Chloroplast transformation efficiency was found to be increased further (20-fold) with supplemental osmoticum (0.55 M sorbitol and 0.55 M mannitol) in the bombardment and incubation medium. This system provides a highly effective mechanism for introducing and expressing plasmid DNA within higher-plant chloroplasts, and the fact that GUS functions as an effective marker gene now makes many genetic studies possible which were not possible before. PMID- 2103475 TI - Manipulation of beta-glucuronidase for use as a reporter in vacuolar targeting studies. AB - It has been documented that when furnished with an endomembrane signal sequence for the endoplasmic reticulum, beta-glucuronidase (GUS) is N-glycosylated, resulting in the nearly complete loss of enzymatic activity. To enable use of beta-glucuronidase as a reporter protein in secretory and vacuolar targeting studies, one of the two putative N-linked glycosylation sites within the GUS gene was altered by site-directed mutagenesis. The second N-linked glycosylation site was not altered because sequence analysis of nucleotide sequences around the second putative glycosylation site revealed that the published sequence was incorrect, and that no such site existed. PMID- 2103476 TI - Characterization of a novel nodulin gene in soybean that shares sequence similarity to the gene for nodulin-24. AB - A gene encoding for nodulin-16 (N-16) was isolated from a soybean genomic library. Nucleotide sequence analysis of the cDNA and the genomic clone of N-16 indicated that the coding region of this gene is 330 bp long and is interrupted by a single intron of 494 bp. The coding region of the N-16 gene shows a high degree of localized sequence similarity with the coding sequence of soybean nodulin-24 (N-24). Sequence similarity between the two genes is limited to the coding region of 90 bp in the first exon and the first 54 bp in the second exon of the N-16 gene which is repeated as the 2nd, 3rd, and 4th exons in the N-24 gene. The N-24 gene has been postulated to be a result of repeated duplication of an insertion element consisting of the 54 bp exon and the flanking intron sequences. In the absence of sequence similarity in the regions flanking the 54 bp sequence between the N-16 and N-24 genes, the N-16 gene does not appear to be the ancestral gene. Both N-16 and N-24 have a similar hydrophobic amino terminal end suggesting that N-16 like N-24 is targeted to the peribacteroid membrane. Southern analysis of soybean genomic DNA shows the presence of other related sequences to the N-16 gene, one of which is found to be closely linked to it. Analysis of the temporal accumulation of the N-16 transcripts during nodule development in effective and ineffective nodules suggests that N-16 and related genes might differ from leghemoglobin and some other late nodulin genes in their mechanism of regulation. PMID- 2103477 TI - The effect of T-DNA copy number, position and methylation on reporter gene expression in tobacco transformants. AB - Inter-transformant variability in the expression of introduced genes was studied in the R1 and R2 generations of 10 tobacco transformants, produced by Agrobacterium-mediated transformation. In replicated and physiologically equivalent material, tranformants showed considerable variability in the expression of the reporter gene uidA as shown by transcript levels and beta glucuronidase (GUS) activity. However, homozygous R2 material could be investigated for seven of the transformants and among these, and in one line in which two inserts could segregate independently, this inter-transformant variability was reduced to simple bimodal expression. The two levels of expression for GUS activity in leaves were high or low (approximately 2.5 or 0.3 nmol cm-2 min-1 respectively), with no continuous variation. Transformants in the high group had single T-DNA insertions, while those in the low group had multiple T-DNA insertions, at the same or different loci. Within each group, although T DNA was apparently integrated at different sites in the plant genome, there was no evidence of position effects. GUS activity levels of the transformants were very similar in the field and in environmentally controlled conditions under high or low light. Plants with multiple insertions and low expression also tended to have increased methylation of the integrated T-DNA. PMID- 2103478 TI - The intergenic region of maize streak virus contains a GC-rich element that activates rightward transcription and binds maize nuclear factors. AB - Maize streak virus (MSV) is transcribed bidirectionally from an intergenic region and rightward transcription produces an RNA that encodes the coat protein. The intergenic region contains promoter elements required for rightward transcription including an upstream activating sequence (UAS) which endows the promoter with full activity in a maize transient expression system. The UAS contains two GC rich repeats (GC boxes) and a long inverted repeat or hairpin with a loop harboring a TAATATTAC sequence common to all geminiviruses. Deletions through the UAS demonstrated the presence of an element, called the rightward promoter element (rpe1), which is responsible for transcriptional activation. Rpe1 includes the two GC-rich boxes, which are similar in sequence to Sp1 binding sites in mammalian cells, but not the conserved hairpin loop. Rpe1 binds maize nuclear factors in vitro and the characteristics of the binding interaction have been determined by 1) binding competition with oligonucleotides, 2) methidiumpropyl-EDTA footprinting and 3) methylation interference assays. Binding of maize nuclear factors to the UAS generates two major bands, slow and fast migrating bands, in gel retardation assays. Footprinting and factor titration data suggest that the fast bands arise by the binding of factors to one GC box while the slow bands are generated by factors binding to both boxes. The data further indicate that the factors bind to the two GC-rich boxes with little cooperativity and bind on opposite faces of the DNA helix. PMID- 2103480 TI - Intron-mediated enhancement of heterologous gene expression in maize. AB - Chimeric genes containing the coding sequence for bacterial chloramphenicol acetyl transferase (CAT) have been introduced by electroporation into maize protoplasts (Black Mexican Sweet) and transient expression monitored by enzyme assays. Levels of CAT expression were enhanced 12-fold and 20-fold respectively by the inclusion of maize alcohol dehydrogenase-1 introns 2 and 6 in the chimeric construct. This enhancement was seen when the intron was placed within the 5' translated region but not when it was located upstream of the promoter or within the 3' untranslated region. Deletion of exon sequences adjacent to intron 2 abolished its ability to mediate enhancement of CAT gene expression. Northern analysis of protoplasts electroporated with intron constructs revealed elevated levels of CAT mRNA. However, this elevation was insufficient to account for the increased enzyme activity. One explanation of these results is that splicing affects both the quantity and quality of mRNA. PMID- 2103479 TI - Biosynthesis, cDNA and amino acid sequences of a precursor of conglutin delta, a sulphur-rich protein from Lupinus angustifolius. AB - The biosynthesis of conglutin delta has been studied in developing cotyledons of Lupinus angustifolius L. Precursors of conglutin delta formed the major sink for [35S]-cysteine incorporated by developing lupin cotyledons, and these precursors were rapidly sequestered into the endoplasmic reticulum. The sequence of a cDNA clone coding for one such precursor of conglutin delta was determined. The structure of the precursor polypeptide for conglutin delta predicted from the cDNA sequence contained an N-terminal leader peptide of 22 amino acids directly preceding a subunit polypeptide of Mr 4520, together with a linking region of 13 amino acids and a subunit polypeptide of Mr 9558 at the C-terminus. The amino acid sequence predicted from the cDNA sequence showed minor variations from that established by sequencing of the protein purified from mature dried seeds (Lilley and Inglis, 1986). These were consistent with the existence of a multi-gene family coding for conglutin delta. Comparison of the sequences of conglutin delta with those of other 2S storage proteins showed that the cysteines involved in internal disulphide bridges between the mature subunits of conglutin delta, were maintained throughout this family of proteins but that little else was conserved either at the protein or DNA level. PMID- 2103481 TI - A 268 bp upstream sequence mediates the circadian clock-regulated transcription of the wheat Cab-1 gene in transgenic plants. AB - We previously reported that the expression of the wheat Cab-1 gene is regulated by an endogenous circadian rhythm and by the photoreceptor phytochrome both in wheat and in transgenic tobacco plants. To define regulatory elements necessary for the circadian rhythm-regulated Cab-1 gene expression, we now analysed the fluctuation of steady-state mRNA levels in a series of 5' deletion mutants in transgenic tobacco plants. We found that the expression of a deletion mutant containing 211 bp upstream sequence still exhibited circadian rhythm. Furthermore we show that an enhancer-like sequence of the Cab-1 promoter (from -357 to -90) can endow a chimaeric gene consisting of a truncated 35S promoter (from -90 to +8) and the bacterial beta-glucuronidase (GUS) gene with circadian clock regulated gene expression. Finally we demonstrate by nuclear run-off experiments that the transcription rates of the Cab genes in wheat oscillate in a rhythmic manner, with a periodicity of approximately 24 hours. Consistent with our previous findings these results (i) indicate that the expression of the wheat Cab 1 gene is regulated mainly at the transcription level and (ii) identify a short promoter region between -211 and -90 that is responsible for the circadian clock regulated gene expression. PMID- 2103482 TI - The complete nucleotide sequence of the intergenic spacer between 25S and 17S rDNAs in rice. PMID- 2103483 TI - Nucleotide sequence of the 7K gene of carnation latent virus. PMID- 2103484 TI - Structure and expression of a tobacco beta-1,3-glucanase gene. AB - We determined the primary structure of a tobacco beta-1,3-glucanase gene. The beta-1,3-glucanase gene has a single large intron, and the intron separates coding regions of the signal peptide and the mature enzyme. Analysis of the 5' flanking region sequence revealed an 11 bp GC-rich element with perfect homology to the putative regulatory sequence of tobacco chitinase genes. RNA blot analysis showed that levels of mRNAs of beta-1,3-glucanase and chitinase are coordinately increased in response to ethylene and salicylic acid. Accumulation of beta-1,3 glucanase mRNA in suspension-cultured cells is rapidly induced at late logarithmic growth phase. Members of the tobacco beta-1,3-glucanase gene families are classified into two subfamilies. One of the subfamilies appeared to be transcriptionally inactive. PMID- 2103485 TI - Nucleotide sequence of a wheat chloroplast gene encoding the proteolytic subunit of an ATP-dependent protease. PMID- 2103486 TI - Isolation and analysis of the major latex protein genes of opium poppy. PMID- 2103488 TI - Stromelysin/transin and tumor progression. AB - Transin is an oncogene-inducible protein which has been shown to be the rat homologue of an extracellular matrix-degrading metalloproteinase known as stromelysin. The activity of transin/stromelysin is regulated at several levels: (1) at the transcriptional level, it is positively regulated by oncogenes, tumor promoters, and certain growth factors, and is negatively regulated by several agents including glucocorticoids and transforming growth factor-beta; (2) the protease activity is produced by processing of an inactive precursor form to an active enzyme; and (3) total protease activity is modulated by activity of tissue inhibitors of metalloproteinases (TIMPs). The association of transin/stromelysin expression with tumor progression suggests that it plays an important role in cancer. PMID- 2103487 TI - The beta-tubulin gene family in Zea mays: two differentially expressed beta tubulin genes. AB - Maize beta-tubulins are encoded by a large multigene family with at least nine members, as determined by Southern blot analysis. Two expressed genes, represented by the beta 1 genomic clone and the beta 2 cDNA clone, were examined in this study. The two genes encode beta-tubulins which show 94% sequence identity at the amino acid level. Maize beta 1 transcript levels were highest in seedling root tip and tissue culture cells, which are both rapidly dividing tissues. No transcripts were detected in non-dividing leaf tissue. In contrast, beta 2 transcripts were present at relatively high levels in tissue culture cells and at lower levels in seedling root tip and leaf tissue. The electrophoretic mobility of the beta 2 polypeptide was examined in relation to the constellation of beta-tubulin polypeptides on two-dimensional gel western blots of a maize pollen total protein extract. No evidence for post-translational modification of the beta-tubulin polypeptides was found in pollen. PMID- 2103489 TI - The role of cathepsin L in malignant transformation. AB - Procathepsin L is the major excreted protein of malignantly transformed mouse fibroblasts and it is one of the major acid cysteine proteases in mammalian cells. The broad general protease activity of cathepsin L against a variety of extracellular matrix proteins as well as other intracellular protein substrates, and its regulation by factors which stimulate growth, suggest that it contributes to the transformed phenotype. Possible functions in antigen processing, invasiveness, metastasis, and turnover of intracellular and secreted proteins involved in growth regulations have been proposed. PMID- 2103490 TI - Cathepsin B and cystatins: evidence for a role in cancer progression. AB - The cysteine proteinase cathepsin B has been implicated in the progression of tumors from a premalignant to a malignant state. Activity of cathepsin B has been shown to be elevated in parallel with malignancy or metastatic potential of human and rodent tumors. These increases in cathepsin B activity correspond in part to increases in mRNA for cathepsin B and in part to reduced regulation by endogenous low Mr cysteine proteinase inhibitors. Most properties of tumor cathepsin B appear to be similar to those of cathepsin B from normal tissues. However, the subcellular distribution of cathepsin B is altered in tumors, resulting in association of cathepsin B with plasma membrane fractions or in release of high Mr forms of cathepsin B into the extracellular milieu. Since cathepsin B can degrade laminin, fibronectin and type IV collagen, we speculate that the presence of cathepsin B at the surface of tumor cells may contribute to the local dissolution of basement membrane observed during tumor cell extravasation. Direct evidence that cathepsin B plays a role in cancer progression awaits studies in which upregulation or downregulation of the expression of cathepsin B and its endogenous inhibitors is found to alter tumorigenesis, metastatic potential, etc. PMID- 2103491 TI - Biological and clinical significance of cathepsin D in breast cancer. AB - Cathepsin D is an acidic lysosomal protease present in all cells. In breast cancer cells, pro-cathepsin D expression and secretion are markedly increased and its processing is altered. This protease is induced by estrogens and growth factors. In vitro, pro-cathepsin D is an autocrine mitogen on breast cancer cells and can be auto-activated to degrade extracellular matrix and proteoglycans in acidic microenvironment. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in lymph node-negative tumors. These results suggest that derouting and overexpression of cathepsin D plays an important role in invasion and metastasis of breast cancer cells. PMID- 2103492 TI - Metalloproteinases and cancer invasion. AB - The invasion and metastasis of cancer cells is a complex multistep process involving attachment of tumor cells to the basement membrane, proteolysis of the local connective tissue stroma, and migration through the proteolyzed stroma. Recent evidence implicates metalloproteinases such as type IV collagenase and transin/stromelysin in the proteolytic aspects of this process. Type IV collagenase activity is modulated by tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2). Immunohistochemical and biochemical studies of several human tumors show correlations between invasive potential and type IV collagenase activity. PMID- 2103493 TI - Application of antibodies in the flow cytometric analysis of benign and malignant cells. AB - The application of (monoclonal) antibodies in the dualparameter flow cytometric analysis of cells, either benign or malignant, can on the one hand facilitate the recognition of their type or degree of differentiation, and on the other hand allow the quantification of cell populations at different stages of the cell cycle or with certain cell biological characteristics. The usefulness and advantages of this approach are illustrated here on the basis of studies with antibodies to specific keratins which make up part of the epithelial cytoskeleton. PMID- 2103494 TI - Carbohydrate antigen expression in colorectal cancer. AB - Several major alterations in glycosylation of glycoproteins and glycolipids occur in colorectal cancer resulting in the expression of cancer associated antigenic epitopes. These changes can occur either in the outer peripheral, middle, or inner core regions of the carbohydrate side chains. The major changes are increased expression, inappropriate expression, deletion and modification of antigenic structures present in normal colorectal tissues. These changes are illustrated by recent studies on the expression of several blood group antigens such as A,B,H, and Leb antigens, modified blood group related antigens such as sialosyl Lea, CA 50, SPan-1, Lex (X) and Ley (Y) antigens and inner core carbohydrate antigen such as T, Tn and Sialosyl-Tn antigens. These changes also occur in adenomatous polyps and appear to correlate with parameters of malignant potential. Thus, these carbohydrate antigens may serve as premalignant markers which may be useful in identification and screening of subjects at high risk for developing colorectal cancer. Carbohydrate containing cancer and malignant markers show considerable promise as potential candidates in immunodetection, staging and therapy of colorectal cancer. PMID- 2103495 TI - Ki-67 and other proliferation markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies. AB - The aim of this study is to briefly review proliferation markers that can be applied in immunohistochemistry, with special emphasis on the monoclonal antibody Ki-67. This antibody reacts with a nuclear antigen present in all proliferating cells which are in the active parts of the cell cycle, i.e. G1, S, G2, and mitosis, but which is absent in G0 cells. Thus, with the help of this antibody a determination of the growth fraction of a given human cell population is possible. The use of this method in human tumor diagnostics is illustrated by three examples: malignant melanoma, breast carcinoma, and malignant Non-Hodgkin lymphoma. The results show that evaluation of the growth fractions by Ki-67 is not only a diagnostic importance, but also has independent prognostic value. In addition, preliminary data on the immunobiochemical characterization of native and recombinant Ki-67 antigen are presented. In immunoblot analysis, Ki-67 detects a doublet with apparent molecular weights of greater than 300 kDa. Furthermore, our data show that cDNA clones isolated from Lambda gT11 cDNA libraries encode for parts of the Ki-67 antigen and must contain the sequence that encodes for the epitope recognized by the Ki-67 antibody. PMID- 2103496 TI - Detection, characterization and tumorigenicity of disseminated tumor cells in human bone marrow. AB - Monoclonal antibodies have been used to detect tumor cells in bone marrow of patients with neuroblastoma, breast cancer, small cell lung cancer, prostatic cancer and gastrointestinal carcinoma. By comparative analysis immunocytology proved to be more sensitive than conventional cytology and histology and had the additional advantage of specificity. A positive correlation exists between the presence of tumor cells in bone marrow and the extent of the primary tumor. The proliferative potential of the micrometastatic cells was assessed by characterization of EGF and transferrin receptors, tumorigenicity was shown by xenotransplantation experiments in nu/nu mice in a few instances. First follow-up studies indicate that the presence of disseminated tumor cells in bone marrow can be taken as predicting the subsequent development of overt metastasis. PMID- 2103497 TI - Biological and clinical perspectives of cancer imaging and therapy with radiolabeled antibodies. AB - Cancer and other diseases that elaborate increased quantities of antigenic substances can be targeted with suitable antibodies labeled with radionuclides. Factors influencing this targeting include the nature, pharmacology, and physiology of the antibodies, the composition and physiology of the tissue targets, the character and linkage of the radionuclide to the antibody, the choice of radionuclide, and the method of administration of the radioimmunoconjugate. The current state of cancer imaging with gamma-emitting radiolabeled antibodies, using the more optimal Fab' antibody fragments conjugated with 99mTc and imaging by single-photon emission computed tomography, permits high detection rates (90% range) of tumors at or below 0.5 cm, thus disclosing lesions missed by conventional radiographic methods. In radioimmunotherapy, severe limitations are due to low antibody accretion in tumors (resulting in low target rad doses), inadequate conjugation of radiometals to antibodies, high red marrow toxicity, and human anti-antibody responses when foreign immunoglobulins are administered. However, radiosensitive tumors, such as lymphomas, have shown impressive clinical responses. PMID- 2103498 TI - Antibodies in diagnosis and therapy. The magic bullet--nearing the century mark. AB - A truly successful magic bullet therapy for cancer requires the production of agents which can easily reach, accurately recognize and permanently nullify every cancer cell in the body. Moreover, these precise functions must be achieved without adversely affecting normal vital tissues. This demanding approach is examined from the standpoint of animal model systems which satisfy these criteria to various extents. The salient features which contribute to success in these models are presented to provide a basis for evaluating the performance of currently available agents, and to assist in the design of new, more highly perfected 'bullets'. Pertinent issues regarding the therapeutic impact of cellular receptors, internalization pathways, mechanisms of toxin action, kinetics of cell killing, solid tumor penetration, pharmacokinetics and relative potency on target versus non-target cells are all considered. Current strategies using advanced biotechnical approaches to construct more effective targeted agents are addressed in this context. PMID- 2103499 TI - Human monoclonal antibodies and engineered antibodies in the management of cancer. AB - In an attempt to obtain more specific and less immunogenic monoclonals for cancer therapy considerable effort has been devoted to the development of human monoclonals. Although this has resulted in the generation of many antibody secreting cell lines they rarely produce useful levels of specific antitumour antibodies. An alternative approach is the humanisation of rodent antitumour monoclonals using genetic engineering techniques. The chimaeric antibodies produced may exhibit reduced immunogenicity and improved Fc mediated interactions. Finally a number of procedures have also been employed to generate so-call bispecific monoclonal antibodies which offer novel therapeutic possibilities. PMID- 2103500 TI - Cellular and viral ligands that interact with the EGF receptor. AB - The growth regulatory functions of a family of structurally related polypeptides are mediated through the membrane-bound epidermal growth factor receptor molecule. This ligand family includes epidermal growth factor, transforming growth factor-alpha, amphiregulin, and polypeptides encoded by several poxviruses. The structural and functional properties that are characteristic of the ligand family provide a basis for possible evolutionary relationships among the various ligands. PMID- 2103501 TI - Transforming growth factor alpha: expression, regulation and biological action of its integral membrane precursor. AB - Transforming growth factor alpha (TGF alpha) is a 6 kDa polypeptide mitogen that interacts with the epidermal growth factor receptor and activates its intrinsic tyrosine kinase. The mature 50 amino acid TGF alpha is released from a 159 or 160 amino acid integral membrane glycoprotein precursor, denoted proTGF alpha, via cleavage at both termini by an unknown protease with elastase-like specificity. Rat proTGF alpha is encoded by a 4.5 kb mRNA that is transcribed from a gene containing 6 exons and spanning 85 kb of DNA. Expression of TGF alpha is most prevalent and abundant in transformed cells and tumors, but also detectable at modest levels in a limited number of normal cells and tissues. In many neoplastic cells, proteolytic processing of proTGF alpha is incomplete and/or inefficient, resulting in the preponderance of soluble and/or membrane-bound forms larger than the mature TGF alpha. To characterize the biological activities of the transmembrane TGF alpha precursor in the absence of processing, amino acid substitutions were introduced at the cleavage sites by site-directed mutagenesis of the rat TGF alpha cDNA. Fibroblasts expressing the mutant proTGF alpha constructs did not secrete TGF alpha, but did accumulate proTGF alpha at the cell surface. Coincubation of these cells with A431 cells resulted in binding and autophosphorylation of EGF receptors, and mobilization of intracellular calcium in A431 cells, demonstrating that the transmembrane proTGF alpha can activate EGF receptors on adjacent cells, leading to signal transduction. In addition, rat fibroblasts constitutively expressing the wild-type or mutant proTGF alpha became morphologically transformed in culture, and induced tumors in nude mice. Thus, the interaction between membrane-anchored ligand and receptor triggers mitogenesis that can culminate in neoplastic transformation. To characterize the physiological and pathological effects of TGF alpha in vivo, particularly with respect to epithelial cells, transgenic mice were developed which overexpress the growth factor in multiple or specific tissues. Widespread overexpression of TGF alpha driven by the metallothionein promoter induced epithelial hyperplasia in several organs, including liver and intestine, without disrupting normal tissue architecture. In contrast, the pancreas displayed increased proliferation of both acinar cells and fibroblasts, and focal alteration of acinar cell differentiation. This pancreatic hyperplasia, fibroplasia, and metaplasia were reproduced when TGF alpha expression was placed under control of the elastase promoter, and thus locally restricted to acinar cells, suggesting autocrine and/or paracrine mode of action. Finally, overexpression of TGF alpha promoted neoplastic transformation of certain epithelia. In coagulation gland, there was dramatic hyperplasia and dysplasia with focal evidence of carcinoma in situ.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2103502 TI - Epidermal growth factor receptor regulation and function. AB - The epidermal growth factor (EGF) receptor is a transmembrane, cell-surface glycoprotein that mediates the mitogenic action of a family of ligands, including EGF and transforming growth factor alpha (TGF alpha). Perturbation of this signal transduction pathway by exposure to excess ligand, by overproduction of the normal EGF receptor, or by the presence of specific mutated forms of this receptor can result in dramatic alterations in cellular phenotype, including malignant transformation. Overstimulation of normal cells is avoided by precise control of the synthesis and degradation of EGF receptors. Regulation occurs at multiple levels, including transcriptional control. A number of DNA-binding proteins have now been identified which positively and negatively modulate EGF receptor gene transcription. PMID- 2103503 TI - Tyrosine phosphorylation and the regulation of cell growth: growth factor stimulated tyrosine phosphorylation of phospholipase C. AB - The significance of tyrosine phosphorylation in cell growth and transformation has been addressed. While the details of how tyrosine kinases actually function in mitogenic signal transduction is not fully understood, recent evidence suggests that phosphoinositide metabolism may have a significant role in growth factor signal transduction. Interestingly, one of phosphatidylinositol-specific phospholipase C isozymes is an excellent substrate for growth factor receptor tyrosine kinases. In this review, the current understanding of growth factor mediated phosphoinositide metabolism and tyrosine phosphorylation of phospholipase C, is discussed. PMID- 2103504 TI - TGF alpha in normal physiology. AB - This paper reviews our work on the localization of transforming growth factor alpha (TGF alpha) in normal adult tissues and the regulation of its synthesis and that of its receptor. We detected TGF alpha immunohistochemically in brain neurons and showed the TGF alpha mRNA derived from the human brain stem is virtually identical to the mRNA derived from human renal tumour cells. In cells derived from anterior pituitary glands, another site of TGF alpha expression, TGF alpha secretion and mRNA levels can be regulated by phorbol esters. The expression of the epidermal growth factor (EGF) receptor, which is also the TGF alpha receptor, is also stimulated by phorbol esters. Similar stimulation of receptor and ligand expression in human breast cancer cells was shown in response to phorbol esters and EGF. The ability of ligand to stimulate its own synthesis and that of its receptor suggests the presence of an autocrine positive feedback loop, however we were unable to break this loop in the breast cancer cells by antibodies that blocked the interaction of TGF alpha with the EGF receptor. The ability of EGF to stimulate EGF receptor and TGF alpha expression appears to require protein kinase C, since inhibition of this enzyme blocked the ability of EGF to stimulate these genes. These studies raise the possibility that hormones capable of activating protein kinase C could stimulate EGF receptor and TGF alpha expression. PMID- 2103505 TI - Epidermal growth factor: receptor and ligand expression in human breast cancer. AB - The epidermal growth factor (EGF) gene is expressed by most human breast cancer cell lines as well as 83% of human breast cancers in vivo. Furthermore, EGF mRNA is detectable in normal human breast tissue. These data suggest that EGF may have a functional role in both normal and neoplastic human breast tissue. Expression of EGF was generally highest in steroid receptor positive human breast tumor biopsies and cell lines. EGF expression was increased by progestins in T-47D and ZR 75 human breast cancer cells. Furthermore, progestins specifically increased the level of TGF-alpha and EGF-receptor mRNA in T-47D cells. Under these same conditions progestins inhibit growth of the cells. Regulation of expression of EGF, TGF-alpha and the EGF-receptor is unlikely to be directly related to the mechanism of progestin induced growth inhibition in T47-D cells. T-47D-5 cells are more sensitive than T-47D cells to progestin and antiestrogen induced growth inhibition. T-47D-5 cells do not express EGF and contain very low levels of TGF alpha mRNA. The higher level of EGF and TGF-alpha expression in T-47D cells may be one mechanism by which these cells decrease their sensitivity to growth inhibition by progestins and antiestrogens. PMID- 2103506 TI - Implications of erbB-2 overexpression for basic science and clinical medicine. AB - Overexpression of the Epidermal Growth Factor (EGF) Receptor gene and the related erbB-2 gene has been identified in human cancers derived from a variety of tissues. The overexpression of the encoded growth factor receptor proteins is functionally related to the development of the tumor. This observation has important potential consequences for the improved diagnosis and treatment of cancer. Overexpression of these proteins also provides experimental systems that facilitate the study of growth factor signal transduction. PMID- 2103507 TI - The epidermal growth factor receptor as a target for therapy with antireceptor monoclonal antibodies. AB - The epidermal growth factor (EGF) receptor is a potential target for antitumor therapy, because it is expressed at high levels on many human tumor cells and appears to be involved in autocrine stimulation of cell growth in a number of experimental studies. Anti-EGF receptor monoclonal antibodies (MAbs) which block ligand binding can prevent the growth in culture of cells that are stimulated by EGF or TGF-alpha. Growth of human tumor xenografts bearing high levels of EGF receptors is also inhibited. A Phase I trial in patients with squamous cell carcinoma of the lung has demonstrated the capacity of a single dose of 120 mg anti-EGF receptor MAb to localize in such tumors and to achieve saturating concentrations in the blood for more than 3 days, without causing toxicity. PMID- 2103508 TI - The myc gene family proteins and their role in transformation and differentiation. AB - Several genes within the mammalian genome share homology with the transforming gene, v-myc, of the avian myelocytic leukemia viruses. Of these, c-myc, Nmyc and Lmyc have been shown to possess transforming activity in vitro and each is found to be aberrantly expressed in a variety of tumours. In normal tissues, expression of Nmyc and Lmyc is restricted to embryonic development and a few adult tissues whereas c-myc and Bmyc are very widely expressed. The proteins encoded by the various myc genes share substantial sequence homology. c-, N and Lmyc proteins are all nuclear phosphoproteins that possess very short biological half lives and bind DNA. All three possess identifiable motifs present in a number of other nuclear proteins involved in transcriptional regulation, and the possible role of myc proteins in gene regulation is discussed. Some experiments, however, favour a different role for c-myc, in DNA replication. Whatever their precise molecular functions may be, it is clear that myc genes play an essential role in the regulation of cellular proliferation. PMID- 2103509 TI - The myb genes. AB - The v-myb oncogene and its cellular progenitor c-myb are both DNA binding proteins capable of transcriptional activation, and are implicated in the regulation of the switch between growth and differentiation in hematopoietic cells. Studies attempting to define the oncogenic determinants of v-myb and activated c-myb genes implicate N- and/or C-terminal truncation as important; both these events appear to increase the affinity of the myb protein for DNA. Myb like genes have been found in organisms ranging from yeast, through plants, to humans; in the more distantly related cases, only the myb DNA binding domain, situated at the N-terminus of the protein, has been conserved. PMID- 2103510 TI - Structure and activities of the ski oncogene. AB - The ski oncogene is the transforming gene, v-ski, of the defective SKV avian carcinoma viruses. V-ski transformation causes increased proliferation of embryo fibroblasts and also induces a number of genes characteristic of the muscle lineage. In natural SKV isolates the 49 kDa v-ski polypeptide is expressed as a fusion protein with N-terminal gag and other viral sequences. The cellular homologue of v-ski, c-ski, is a large gene comprising at least 70 kb and containing at least seven coding exons. V-ski consists of most of the first five coding exons of c-ski. The proteins encoded by both genes are nuclear proteins that bind DNA and contain recognised motifs common to known nuclear regulatory proteins. A c-ski-related gene called sno has also been recently identified and, like c-ski, it is expressed in several human tumour cell lines. PMID- 2103511 TI - The rel gene and its role in oncogenesis. AB - The rel oncogene induces rapidly fatal lymphomas in birds. The mechanism by which this occurs is not clear, but investigations into the properties of rel have shown it to be an unusual protein. Unlike other 'nuclear' oncogenes described in this issue, v-rel can be found in both the cytoplasm and nucleus. In addition, it appears to transform avian lymphoid cells regardless of its localization. Interestingly, the rel gene is highly homologous to the Drosophila gene dorsal, which is involved in determination of dorsal-ventral polarity in the developing embryo. In this review, the biology of the virus containing the rel oncogene, REV T, will be described. The structure of the gene and the properties of the rel protein will be examined. The rel protein will be compared to the Drosophila homolog, dorsal, both structurally and functionally. PMID- 2103512 TI - Transformation by the human adenoviruses. AB - Oncogenic transformation by the human adenoviruses involves the concerted action of two genes, E1A and E1B. Over the last few years the products of these genes have been characterised in considerable detail using genetic, immunological and biochemical means. The E1A gene by itself can immortalise primary cells and can cooperate to effect full morphological transformation not only with E1B but also with other known oncogenes. The immortalisation and cooperation activities of E1A require multiple functions that are directed by structurally and functionally independent regions of the E1A protein. These regions coincide with sites of protein: protein interaction between E1A and a variety of cellular polypeptides. One of these, the Rb protein, is a known regulator of the mammalian cell cycle. The E1B region encodes two proteins required for transformation, the larger of which binds to the p53 cellular protein. This protein has also been implicated as a negative regulator of cell growth. It appears therefore that E1A and E1B carry out their many functions associated with transformation at least in part by binding to and presumably modulating the activity of key cellular regulators. PMID- 2103513 TI - Intralumenal sarcoplasmic reticulum Ca(2+)-binding proteins. AB - The sarcoplasmic reticulum (SR) controls the level of intracellular Ca2+ in cardiac and skeletal muscle by storing and releasing Ca2+. A set of intralumenal SR Ca(2+)-binding proteins has been identified that may serve important roles in SR Ca2+ storage and mobilization. The most prominent of these SR proteins, calsequestrin, is discretely localized to junctional SR. Other intralumenal proteins are more widely distributed throughout the SR. All of these intralumenal SR Ca(2+)-binding proteins are acidic, stain blue with dye Stains-All, and appear to be substrates for casein kinase II. The biochemistry and cell biology of lumenal SR proteins may conform to a paradigm now emerging from the study of endoplasmic reticulum proteins. PMID- 2103514 TI - Rapidly exchanging Ca2+ stores of non-muscle cells. AB - The rapid and transient redistribution of calcium from intracellular stores is a key event of cell activation. The nature and molecular composition of intracellular Ca2+ stores of non-muscle cells are the object of intense investigation. In this paper, we review: (a) the experimental evidence in favor of the existence of intracellular, membrane-bound compartments specialized for uptake, storage and release of calcium, (b) the main protein components of rapidly exchanging Ca2+ stores, i.e. Ca2+ pump, intralumenal Ca2+ binding proteins (calsequestrin, calreticulin, etc.) and Ca2+ channels sensitive to either inositol 1,4,5-trisphosphate or Ca2+, caffeine and ryanodine, and (c) the relationship between Ca2+ stores and the endoplasmic reticulum. PMID- 2103515 TI - Regulation of intracellular calcium in epithelial cells. AB - The role of [Ca2+]i as a second messenger in non-excitable cells has been appreciated for almost 3 decades. The advent of fluorescent Ca2+ indicators has allowed the monitoring of Ca2+ signalling in suspensions of these cells. Agonist mediated changes in [Ca2+]i usually show an initial Ca2+ transient followed by a maintained increase. The former has been shown to be due to Ca2+ release from one or more intracellular stores, the latter due to activation of receptor operated Ca2+ entry (ROCE). More recently it has been recognized that many cells show distinct maintained oscillatory behavior when examined by single cell optical methods. It is proposed here that these oscillations are the consequence of IP3 and Ca2+ stimulation of Ca2+ release and ligand activation of ROCE followed by Ca2+ inhibition of Ca2+ and ROCE as Ca2+ pumps are activated. These oscillations allow more exact regulation of a pump/leak controlled second messenger such as [Ca2+]i. PMID- 2103516 TI - Calcium oscillations: phenomena, mechanisms and significance. AB - Many hormones that mobilise intracellular calcium via inositol 1,4,5 trisphosphate induce oscillations in cytoplasmic free Ca. Two basic oscillatory patterns occur: quasi-sinusoidal oscillations and repetitive free Ca transients. The mechanisms responsible for generating these oscillations are not clear; calcium-induced calcium release, interplay between two intracellular calcium pools and repetitive generation of InsP3 are discussed. The significance of different oscillatory patterns induced by different agonists in the same cell is emphasised, and mechanisms by which the oscillators may retain-receptor specific information are proposed, such as negative feedback onto receptors or G-proteins by protein kinase C. Reasons why cells generate free Ca oscillations and possible consequences such as oscillations in downstream pathways are explored. The possibility that pathological conditions such as aluminium toxicity are exerted through distortion of oscillatory free Ca signalling is raised. PMID- 2103517 TI - Benzoxazinone kanamycin A conjugate. A new fluorescent probe suitable to detect mycoplasmas in cell culture. AB - The synthesis of a new benzoxazinone derivative suitable to detect early infection of cultured cells with mycoplasmas is described. p-[beta-(7 dimethylamino 1,4-benzoxazin 2-one 3yl)-vinyl]- phenylpropenoic acid was coupled to kanamycin A, an aminoglycoside leading to a cationic fluorescent probe which fluoresces at 600 nm upon excitation at 490 nm. This fluorescent probe is shown to heavily label the glycocallix of all the mycoplasma strains tested which are found to be associated with contaminated cultured cells and to allow an easy and rapid detection of contamination by fluorescence microscopy and flow cytometry. PMID- 2103518 TI - Image analysis of the chromatin organization in the nuclear domains of freeze fractured hepatocytes and lymphocytes. AB - The complex organization of the interphase nucleus can be analyzed, by way of thin sectioning and also freeze-fracture. This approach has previously been utilized in association with image analysis to quantitatively describe the organization of isolated rat liver nuclei and nuclear matrices. The main nuclear domains which, in section, present marked differences due to their electron density, can be identified in replicas with more complex procedures, based on the quantitative evaluation of the number of particles per unit area and mainly by using image analysis. A quantitative analysis of the nuclear substructures has been performed by way of image analysis on in situ nuclei of freeze-fractured cells presenting marked differences in the heterochromatin quantity, such as hepatocytes and lymphocytes. The replicated nuclear particles have been classified according to their diameter and the obtained histograms have been quantitatively evaluated. The nuclear domains, heterochromatin, interchromatin, nucleolus, present characteristic ratios among the three main classes of particles; that is, ribonucleoproteins, solenoid filaments and solenoid fibre aggregates. The typical patterns of the nuclear domains can be further stressed by selecting a single class of particles and by examining its topographic localization. While interchromatin and nucleolar domains present a similar quantitative pattern in hepatocytes and lymphocytes, the heterochromatin of lymphocytes contains a significative higher percentage of solenoid aggregates than that of hepatocytes. PMID- 2103519 TI - An efficient isolation procedure of Ca-tolerant ventricular myocytes from ferret heart for applications in electrophysiological studies. AB - A simple procedure which provides a large yield of isolated ferret ventricular myocytes is described. The enzymatic dissociation was performed by perfusion of the whole heart with the "Langendorff method" at 37 degrees C, without an incubation period. Special attention was given to the period of perfusion with Ca free or low-calcium containing solutions and to the proportion of both collagenase and elastase used. The viability and calcium tolerance of the isolated cells were tested by ultrastructural and electrophysiological studies. Photo-microscopy showed that 60 to 80% of the isolated cells had an elongated shape (18 microns in diameter, 150 microns in length) and did not beat spontaneously in normal Tyrode solution. The morphological and ultrastructural integrity of these cells was shown in SEM by their smooth surface with regularly spaced T-tubule openings and in TEM by the regular distribution of the transverse tubular system, mitochondrium and sarcomeres. Using the whole-cell patch-clamp technique, they had a resting membrane potential of -72 mV, two types ("Purkinje like" and "ventricular like") of action potentials could be elicited and they were correctly affected by well-known modulators of calcium channels. This technique was successfully applied to the rat heart and could be used for heart dissociation of small mammals. It can simultaneously provide isolated cells of different regions of the heart and can be easily and routinely used by any investigator. PMID- 2103520 TI - Effects of a series of homologous alpha,omega-dimethylaminoalkanes on cell proliferation: binding and uptake of putrescine by a human glioblastoma cell line (U251) in culture. AB - The first step of polyamine uptake is the binding of polyamines to the cell membrane. In order to characterize the specificity of the putrescine binding sites at the surface of the glioblastoma cells (U251), we have carried out competition experiments between putrescine bound to latex microspheres and vizualized by scanning electron microscopy and a series of N,N'-tetramethyl alpha,omega-diaminoalkanes. N,N'-tetramethyl-1,4-butanediamine (N,N' tetramethylputrescine) and higher homologs inhibit the latex putrescine binding to the cell surface and concomitantly cell proliferation. [14C] putrescine uptake was mainly inhibited by the lower homologs, which were devoid of antiproliferative effects. Our results suggest that putrescine uptake by the human glioblastoma cell line U251, and putrescine binding to the surface of these cells are independent processes. The potential relationship between antitumor effect of N,N'-tetramethyl-alpha,omega-diaminoalkanes and its binding to a specific putrescine acceptor site is discussed. PMID- 2103521 TI - Microcalorimetric investigations on human leukemia cells--Molt 4. AB - Heat production by leukemia cells Molt 4, growing in suspensions with 1 and 3 x 10(5) cells/ml for 4 days, was studied by microcalorimetry. Heat production rates were related to cell growth, glucose consumption, lactate production and cellular ATP-content. The results show that the time course of heat dissipation is dependent on initial cell number. However, observed thermal power maxima were fairly identical in all experiments. Heat production rates per cell were similar during the initial phase of the study independently of initial cell number, while higher cell densities resulted in significantly lower rate of heat production. Glycolytic conversion of glucose into lactate is nearly stoichiometric. Our results indicate a relationship between heat production and amounts of glucose and lactate in the medium. ATP concentration in cells decreased after 24 hours of culture. PMID- 2103522 TI - Ultrastructural localization of fibronectin mRNA in chick embryo by in situ hybridization using 35S or biotin labeled cDNA probes. AB - We have studied the expression of the fibronectin gene in 7 day-old chick embryo (stage 32) by in situ hybridization at the light and electron microscope levels, using a 397 base-pairs chicken cDNA, labeled by radioisotope or biotin-11dUTP. Cryostat sections of whole chick embryos displayed a selective label on the upper layer of the dermis, fibrous sclera and mesenchymal cells but not on cartilagenous sclera cells. These results show that the expression of the fibronectin gene varies in relation to the morphogenetic events. Hybridization at the ultrastructural level on thin sections of sclera embedded in Lowicryl K4M showed a selective labelling on various cell compartments. Biotin-11dUTP and radiolabeled probes were compared. The labeling was found precisely on the membrane of the rough endoplasmic reticulum and on the nuclear envelope. A few silver grains were located on the nucleus and in the perinucleolar region. This study shows that the postembedding in situ hybridization is a powerful procedure to study the expression of the extracellular protein genes and gives further information on the localization of mRNA. PMID- 2103523 TI - The role of pH in the intracellular acetylcholine receptor ligand processing. AB - Previous studies have shown that the internalized AChRs are transported through many vesicular compartments: Golgi associated vesicles, coated vesicles, smooth vesicles, endosome-like structures and lysosomes. These compartments have an acidic pH ranging from 4.5 to 6.5. The pH differences between organelles suggests that these differences may influence the sorting and final expression of AChRs. To test this hypothesis, we measured the number of counts of 125I-alpha BTX or 125I-Mab35 dissociated from myotube membranes containing AChRs as a function of pH. Neither the 125I-alpha BTX nor 125I-Mab35 showed an enhanced dissociation in the pH range 4.0-7.0, whereas lowering the pH to 6.0 or below enhanced the dissociation of 125I-alpha 2-macroglobulin from myotubes. In other experiments using Torpedo membrane we showed that neither 125I-alpha BTX nor 125I-Mab35 appreciably dissociated from the AChR unless the pH was less than 4 or above 11. Double-label studies using a novel membrane permeable acidotropic molecule DAMP (3-(2,4 nitroanilino) 3'amino-N-methyl-dipropylamine), facilitated mapping the pH of the intracellular compartments containing internalized AChRs. This molecule accumulates inside acidic compartments in the cell and has a dinitrophenol (DNP) group recognized by DNP specific antibodies. Cells were treated with 30 micrograms DAMP for 30 min and allowed to internalize Mab35-gold (15 nm) for various periods (0-15 h). At each time point we fixed and washed the cells, and incubated with anti-DNP monoclonal antibodies followed by incubation with anti mouse IgG and protein A colloidal gold (5 nm). Different sized gold particles allowed us to simultaneously identify the AChR compartments and estimate their pH. Sister cultures were exposed to acidotropic drugs to destroy pH gradients. Under those conditions, AChR delivery to lysosomes was blocked. Our studies show that AChRs are transported through acidic compartments ranging from pH 4.5 to 6.5 and in contrast to other ligands they do not dissociate from the intracellular membranes at low pH. PMID- 2103524 TI - Fundus changes in chronic membranoproliferative glomerulonephritis type II. AB - Chronic membranoproliferative glomerulonephritis type II (dense deposit disease) is a renal disease characterized by dense deposits in the glomerular and tubular basement membranes. We report a retinopathy with diffuse retinal pigment alterations in 11 out of 12 patients with this disease. Four of the eleven patients also presented disciform macular detachment and choroidal neovascularisation. The lesions were observed at the earliest 1 year after the diagnosis of the renal disease. In a control group of 17 patients with chronic membranoproliferative glomerulonephritis type I none of the patients presented similar fundus lesions. PMID- 2103525 TI - A long term follow up of ocular siderosis: quantitative assessment of the electroretinogram. AB - Siderosis oculi is a severe sequel of retained, iron made, intraocular foreign body. Iron atoms or ions, dissolved from the foreign body, may diffuse to the retina and produce irreversible cellular damage. Therefore, early extraction of an iron foreign body is recommended. When the risks of surgical intervention outweigh the danger of siderosis, the patient is periodically examined in order to detect the initial signs of siderosis. The most commonly used test for quantitative and objective assessment of retinal function is the electroretinogram (ERG). We report here a long term ERG follow-up (about 8 years) of a patient suffering from a unilateral iron intraocular foreign body. The development of siderosis was detected by any of the ERG responses; cone dominated, rod-dominated or mixed cone-rod responses. However, the degree of the assessed damage varied and strongly depended upon the flash intensity used to elicit the ERG response and upon the ERG wave chosen to assess retinal function. The relationship between the ERG b- and a-waves showed a profound deterioration reflecting a reduction in signal transmission from the photoreceptors to the inner nuclear layer. These findings suggested that iron toxicity produced more damage to the inner retina than to the outer retina. PMID- 2103526 TI - Oxygen-induced retinopathy in the newborn rat: a scoring system for the evaluation of retinal vascular changes. Scoring system for OIR in the rat. AB - The authors describe a scoring system they have developed for evaluating damage produced in the retinal vascular network of the newborn rat by exposure to oxygen. India ink-injected retinal flat mounts are used. The scoring system provides for division of the retina into three concentric zones with the optic disk as a center point. Each retinal quadrant is then examined for the presence of the following lesions of progressive severity: vaso-obliteration of the capillary network, loss of the periarteriolar capillary-free zone, newly formed capillary tufts. When more than one type of lesion is present in a quadrant, only the most severe lesion is considered. The numerical score corresponding to that lesion is then multiplied by the factor corresponding to the concentric zone in which the lesion lies to give the quadrant score. The total retinal score is represented by the sum of the four quadrant scores. This type of system, if adopted by other investigators, can facilitate precise and systematic description of the results of different experimental protocols. PMID- 2103527 TI - Changes in macular function throughout adulthood. AB - Recent reports suggest that the neural system is the principal cause of loss of visual function with age and that senile lenticular and pupillary changes are of minor importance. In order to investigate this neural deterioration further we measured Logmar visual acuity and photostress recovery time (PSRT) in 61 subjects over an age range of 19 to 78 years. The magnitude of the PSRT reflects the efficiency with which the visual system recovers from exposure to a glare source and is principally dependent upon the integrity of the photoreceptors and the retinal pigment epithelium. The results indicate that macular function declines significantly throughout adulthood. PMID- 2103528 TI - Pattern dystrophies of the retinal pigment epithelium. The study of three generations in a family. AB - Three members of a family in one generation were affected by a pattern dystrophy of the retinal pigment epithelium. The patients present typical hyperpigmented macular RPE lesions in a butterfly-shaped to (macro-)reticular pattern, and were all asymptomatic. Examination of 26 family members in 3 generations suggests autosomal recessive inheritance. The family showed some cases of congenital deutanomaly, and a female subject presented both disorders. PMID- 2103529 TI - Topically applied levobunolol does not cause changes in the corneal endothelium. AB - The corneal endothelium was examined in ten patients suffering from ocular hypertension before, during and after four months of topical levobunolol treatment. The untreated fellow eye served as a control. The number of endothelial cells, determined with a McIntyre eyepiece and an Eisner's contact lens, was not affected by levobunolol therapy. In addition, the morphology of the cell did not appear to be affected by the drug. PMID- 2103530 TI - The pattern ERG in Best's disease. AB - The aim of this study was to assess inner retinal function in patients with Best's disease using the pattern ERG (PERG). Nine patients with Best's disease, who had good visual acuity, were studied. Five of the nine had abnormal PERGs. All five had some reduction in central visual acuity. We believe that the abnormal PERGs in these patients represents photoreceptor cell loss which is occurring at an early stage in Best's disease. PMID- 2103532 TI - The healing potential of the endodontal-periodontal lesion. PMID- 2103531 TI - Psychophysical and electrofunctional contrast sensitivity in cataractous patients treated with bendazac-lysine salt. AB - The clinical progression of the cataract may be influenced by drugs which reduce the denaturation of lens proteins. One of the most promising drugs is the bendazac-lysine salt. The drug was used in a double-blind study of a group of patients with initial cortical cataract in order to evaluate the changes in visual acuity and contrast sensitivity by means of a psychophysical and an electrophysiological method. After 6 months of treatment with bendazac the mean values of visual acuity showed a statistically significant increase in respect to baseline values, as well as an improvement of the threshold of contrast for most spatial frequencies. In the eyes treated with placebo there was no statistical difference between the visual acuity at baseline and after the treatment, but an increase of the contrast threshold for many spatial frequencies. The treatment with bendazac, when compared to the administration of placebo, leads to a statistically significant improvement of the contrast threshold and induces a global improvement on the visual conditions. PMID- 2103533 TI - Endodontic isolation: rubber dam application for difficult cases. PMID- 2103534 TI - Endodontic radiographic principles. PMID- 2103535 TI - Nonsurgical endodontic treatment of teeth with dens invaginatus. PMID- 2103536 TI - Inhalation sedation (relative analgesia) with oxygen/nitrous oxide gas mixtures: 1. Principles. AB - Inhalation sedation with low-to-moderate concentrations of nitrous oxide in oxygen has a remarkable safety record--in over 45 years of use there has not been any mortality or serious morbidity recorded. It is not surprising therefore that the use of the technique is increasing steadily, as it has been shown to be an effective method of managing patients' anxiety. In this two-part article the author explains the procedure. In Part 1 he reviews the principles of relative analgesia: describing the characteristics of the different planes of sedation, the mechanism of uptake and elimination of nitrous oxide, and the need for scavenging. In Part 2 he will give a detailed practical guide to the modern technique, incorporating the subtle changes that have been developed over the last ten years. PMID- 2103537 TI - An update on endodontics: 2. File manufacture and obturation techniques. AB - In recent years manufacturers have responded to an increase in endodontic treatments by developing a number of new products. New techniques have also been introduced. In this two-part article the author critically reviews these developments. In Part 1 he looked at diagnosis of endodontic problems and at root canal preparation techniques. In Part 2 he now examines file designs together with techniques for root canal obturation. PMID- 2103539 TI - A simple technique for removal of mottling, opacities and pigmentation from enamel. AB - Mottling of teeth can have significant psychological impact on patients- particularly on adolescents, who may be subjected to much unkind teasing. A number of procedures have been suggested for removal of mottling and stains. The authors describe a simple and quick technique using a paste of hydrochloric acid and pumice, and on the basis of their clinical and laboratory experience suggest it as a treatment of first choice. PMID- 2103538 TI - Current issues in the use of fluorides in dentistry. AB - Britain, along with many other developed countries, has experienced a dramatic decline in prevalence of dental caries. This has been attributed to the widespread use of fluoride toothpastes, which has done much to improve children's dental health. Studies indicate that fluoridation of water supplies would confer an additional benefit to dental public health, while other fluoride vehicles (mouthrinses, topical gels and varnishes, tablets and drops) are valuable in preventing caries in high-risk patients. The authors review the issues involved. PMID- 2103540 TI - Aspects of the use and abuse of aesthetic restoratives. 2. Dentine adhesives and glass-ionomer cements. AB - Modern materials offer great promise in the aesthetic restoration of teeth. However, their performance in practice may not fulfil this promise. This is often because of inadequate understanding of the scientific principles behind the new materials, leading to misuse. In Part 1 of this article the author reviewed some of the physical properties of composites, and explained both their proper use and their limitations. In Part 2 he looks at dentine adhesives and glass-ionomer cements. PMID- 2103541 TI - Replacement of missing maxillary canines by resin-bonded bridgework. AB - This report describes the replacement of both upper canine teeth in a young woman patient by means of resin-bonded bridges. While essentially simple, this case demonstrates the importance of careful assessment and planning to achieve the best potential for long-term success. PMID- 2103542 TI - [Diarrheal disease in children]. PMID- 2103543 TI - [Ambulatory surgery in ophthalmology]. AB - Traditionally intraocular ophthalmologic surgery has been performed on hospitalized patients. Nevertheless, surgical advances now allow ambulatory management with the same effectiveness. This communication about our experience with outpatient intraocular surgery shows that there were no complications but several advantages among which is mentioned the optimal use of the hospital facilities, mainly for those patients whose serious condition require hospitalization. PMID- 2103544 TI - [Blood concentrations of immunoglobulins in children with vitamin A deficiency]. AB - The object of this study is to measure the influence that vitamin A has upon seric concentrations of different isotypes of immunoglobulins (IgM, IgG, IgA) in children with a normal nutritional state or a slightly subnormal one, as well as that of patients with lower respiratory infections. Fifty two children were studied over a period of 24 months. Twenty eight of these were from an orphanage, while 24 were hospitalized, due to a low respiratory infection. The patients with lower respiratory infection showed normal average concentration of vitamin A, but under that of the orphanage (p less than 0.025). It was also observed that malnutrition influences the seric concentrations of immunoglobulins, which were higher in normal individuals; never the less, when this group show deficiency of vitamin A the serum concentration of IgM became lower in the orphanage, malnutrition children. In a similar way, a lowering of IgG was observed in patients with lower respiratory infections and vitamin A deficiency, while no alterations were found in the serum concentration of IgG in any of the groups studied with vitamin deficiency. It is concluded that the concentrations of vitamin A and the nutritional state modify serum values of IgM and IgG. PMID- 2103545 TI - [From cyst to cysticercus granuloma using cranial computerized tomography]. AB - Report of one case of neurocysticercosis, treated and followed for three years, that provides a useful clinical-tomographic correlation for judging the pathologic stage of the disease, on the basis of an image-sequence. PMID- 2103547 TI - [Obesity]. PMID- 2103546 TI - [Odontogenic myxoma of the ascending mandibular ramus. Bibliographic review and report of a clinical case]. AB - A case of odontogenic myxoma is reported within a review of the literature. It is suggested that the lesion is of odontogenic origin, also that the precursor cell should be called myxoblastoma . The fact that the myxoma could perforate the cortex and invade the soft tissue is very important for the prognosis and treatment , because it is known that, if a myxoma is originated in the soft tissue, it will be less aggressive. It should be asked for a special stains, within the histopathologic diagnosis, because they are used to differ between this tumor, from the so called "myxomatous degeneration". Speaking of the treatment, a Steinmann nail bent like a 7, was used after the resection, to avoid the facial deformity, keeping in a such a way, the working function. PMID- 2103548 TI - [Enuresis]. PMID- 2103549 TI - [Intraocular lenses]. PMID- 2103550 TI - [Hearing aids]. PMID- 2103551 TI - [Treatment of children with diarrheal disease. I. Basic concepts]. PMID- 2103552 TI - [A model system for emergency medicine for Mexico City]. AB - Trauma and sudden illnesses already represent a capital problem of public health in our country. Since the social and financial costs that we must pay are very high, it is necessary to create an emergency medical system that categorizes both, the patients according to this aims and the available means in order to give them comprehensive and definitive care. This categorization implies quick and appropriate transportation from accidents to the ideal hospital facility and also the prehospital medical care at the scene and during transportation. The system should include two prehospital and two hospital levels, and the highest level being the keystone of the whole. Education and research are fundamental for the harmonic development of the system. PMID- 2103553 TI - [Frontiers of medical education]. PMID- 2103554 TI - [Level of instruction of first-year students in the School of Medicine at the Universidad Nacional Autonoma de Mexico]. PMID- 2103555 TI - [The training of specialist physicians in the School of Medicine of the Universidad Nacional Autonoma de Mexico]. AB - Specialization courses in the medical area purport the preparation of specialists in various branches of medicine, orienting the students in their search for useful knowledge to resolve daily problems in the specialties and forming them for daily practice. These courses take place in different hospitals of the Health Sector within Mexico. Agreements with the National University (UNAM) have been reached with this purpose. Formation and training activities of specialties is a function of the Health Institutions in accord with existent resources and needs. The UNAM forms the specialists in the field where they will be later required. The physicians who are submitted to this training are prepared to practice clinical, institutional, medicine, as well as to teach and do research. The following four elements of the process are emphasized: the students, the teachers, the characteristics of the seat hospitals and the curricula. The programs lead the teaching activities with a tendency to form the expected resources with an establishment of the students and teacher's roles, as well as the teaching methology to be used. The success of these programs is limited because the particular conditions and organization of the hospitals, the characteristics of the teachers and the background of the students. PMID- 2103556 TI - [Infant mortality in Mexico]. PMID- 2103557 TI - [Science, technology and humanism in medicine]. PMID- 2103558 TI - [Thallium poisoning. Experience with 50 patients]. AB - We have studied fifty cases of thallium intoxication during the past nine years. Twenty-eight occurred in women and twenty-two in men. One of the patients was a new born whose mother had this type of intoxication during her third trimester of pregnancy. The ages varied from one day to 84 years and in all cases the source of thallium was ingestion of rat poison, except for the baby who received it across the placenta and an other patient whose source was transdermal. Twenty three of the cases of intoxication were accidental, twenty-one were suicidal attempts and five were homicidal. One case did not know the source of intoxication. Thallium levels were measured in the urine of all the patients, some were measured in blood, as well as cerebrospinal fluid. The main clinical manifestation was a mixed type of severe peripheral neuropathy, with abdominal pain, nausea, vomiting and alopecia and some cases had psychiatric manifestations. Electrophysiological studies and nerve biopsy examined with electron microscopy in three patients. Magnetic nuclear resonance, computerized axial tomography of the abdomen and cranium were performed in two patients. There was only one death and the rest of the patients recovered almost completely. Pathophysiology and pharmacological management of this type of neurointoxication are revised. PMID- 2103559 TI - [Diagnosis, prevention and treatment of renal and urinary tract lithiasis]. AB - Kidney and urinary stone disease is a major public health problem which requires a systemic clinical and biochemical evaluation to establish a precise diagnosis and well oriented therapy. This study reviews the results of a protocol designed to establish the metabolic abnormalities that occurred in 626 consecutive renal stone patients studied in two periods; group I (1979-1987) 441 cases and group II (1987-1989) 185 cases. The group I included the following determinations before and after a five day oral calcium load: serum and 24 hr urine electrolytes, divalent cations, phosphate, uric acid, cystine, glomerular filtration rate, parathyroid function evaluation with PTH and Tm Phosphate and since 1982 also (Ia) cAMP. In group II we also determined inhibitors of crystallization (magnesium and citrate) and promoters of nucleation (oxalate). In 185 cases of group I, we monitored months of follow up after metabolic evaluation and the number of stones formed per patient/year before and after treatment was begun. In group I we detected some variety of metabolic abnormality in 88.2 percent of our patients and in group II increased to 96.2 percent. A two year follow up was recorded in 55 percent and four year follow up in 39 percent of our cases. The stone/patient/year formation rate before treatment was 2.8 and significantly decreased to 0.8 after treatment. The highly diagnostic efficiency, the long term follow up and the adequacy of treatment significantly decreased stone activity in this group of patients. We concluded that this protocol should be included in the systematic evaluation of kidney stone patients. PMID- 2103560 TI - [Quantification of bacteria in the small intestine of malnourished children with chickenpox]. AB - The purpose of the present study was to determine whether a high number of bacteria could be demonstrated in the upper small bowel during the chickenpox infection. Intestinal juice was drawn in nine malnourished children, during and two weeks after the acute period of the disease. The results of the study fail to demonstrate quantitative differences in the bacterial flora of the small bowel in both periods. Besides that, the bacterial overgrowth previously reported in malnutrition, is confirmed. PMID- 2103561 TI - [Alzheimer's disease]. AB - The primary degenerative dementia of Alzheimer type, present denomination, represents a medical, social and economical problem. The early diagnosis, based on medical criteria, might improve some aspects of the expected evolution of these, up to date, hopeless patients. PMID- 2103562 TI - [Cocaine and its endocrine effects]. PMID- 2103563 TI - [Extracorporeal lithotripsy in biliary calculi]. PMID- 2103564 TI - [Treatment of fever]. PMID- 2103565 TI - Environmental control systems in a spinal injuries unit: a review of 10 years' experience. AB - In 1979 a 30-bed spinal injuries unit was opened at Burwood Hospital in Christchurch, New Zealand. The design of the building included built-in environmental control facilities for tetraplegic patients. This paper outlines 10 years of experience with environmental controls in a hospital setting, and discusses some of the problems encountered. Special mention is made of ease of setting up equipment, patient interface switches, patient acceptance, and a major upgrade and modification of the original control system. Although not utilized as much as originally anticipated, a definite need for environmental controls with the spinal injuries unit has become firmly established. PMID- 2103566 TI - Impairment and recovery profiles of sensory-motor function following stroke: single-case graphical analysis techniques. AB - Graphical analysis procedures have been developed to improve interpretation of sensory-motor tests from individual subjects following acute brain damage. The procedures have been applied to 11 unilateral stroke patients assessed serially over 12 months on a computerized quantitative sensory-motor test battery of which grip strength, arm speed, and tracking have been chosen for illustrative purposes. The results indicate that four graphs are necessary to fully demonstrate neurologic impairment and recovery of each sensory-motor function, although fewer graphs would be satisfactory in some applications. Such analyses have proven valuable in the display of serial performance of individual patients but demonstration of impairment and recovery is much more difficult than for group analyses. PMID- 2103567 TI - Leisure activity after stroke. AB - Patients were questioned 40-78 weeks after stroke to ascertain their previous and current levels of leisure participation. The results indicate a decrease with regard to both the number of activities and the frequency of participation when compared to reported pre-stroke leisure activity. PMID- 2103568 TI - ELGAM--extra-laboratory gait assessment method: identification of risk factors for falls among the elderly at home. AB - Gait and balance disturbances are recognized risk factors for falls among elderly persons. The prevention of falls and their adverse complications is one of the challenges in geriatric care, requiring the early detection of risk factors. Heretofore, gait assessment procedures have required considerable investment in equipment for sophisticated biomechanical testing. This has limited the use of gait-testing procedures to the laboratory or clinic. We describe a simple and effective method for at-home or community gait testing, ELGAM (extra-laboratory gait assessment method). ELGAM was field-tested as part of a study of 36 community-dwelling elderly in Beer Sheba, Israel. The ELGAM parameters studied included step length, walking speed, initial starting style of walking, ability to turn head while walking, and static balance. Slow walking speed (less than 0.5 m/s), small steps, difficulty in turning the head, and impaired balance were significantly associated (chi-square analyses, p less than 0.01) with unstable gait. The parameters were also positively associated one with another, except for head turning. The ELGAM parameters were significantly related to self-assessed fall frequency, and reported 'near falls' among women only. In addition, among women only, slow walking speed was associated with depressive symptoms as detected by a validated screening test, the Short Geriatric Depression Scale, and with poor subjective health rating. Among 58% of this independently living elderly sample, ELGAM detected one or more risk factors. ELGAM is a 'low-tech', functionally based, effective method for direct recording of gait parameters that is applicable for community studies of the early detection of risk factors for falls and mobility problems. PMID- 2103569 TI - Accelerometric evaluation of ataxic gait: therapeutic uses of weighting and elastic bandage. AB - Two-dimensional (fore-aft and vertical) acceleration of locomotion was measured in 10 normal subjects and 13 patients with idiopathic olivopontocerebellar atrophy who were ataxic but able to walk without any assistance. Accelerometers were tightly placed on the third lumbar vertebra. Asymmetry and unsmoothness indices of locomotion defined from the line spectra of the accelerometric data were computed. Reproducibility of the indices was checked in the normal subjects and patients. The index values were significantly correlated with visual rating of gait unsteadiness in the patients. The indices for vertical components were significantly increased when subjects walked slowly. Effects of weights and bandages on gait were analysed by the fore-aft components of the indices. They were attached to both lower extremities. Weighting or bandaging did not change, or even increased the index values in most of the normal subjects. The indices were also unchanged in the patients. However, some of the patients showed significant improvement with weights or bandages. Mechanisms of therapeutic effects of weighting and elastic bandages on ataxia are discussed. PMID- 2103570 TI - Influence of cognitive function on social, domestic, and leisure activities of community-dwelling older people. AB - The Frenchay Activities Index (FAI), a brief scale developed to measure lifestyle in stroke patients, was given to 119 community-dwelling people, aged 70 years or older, in order to obtain a baseline estimate of social, domestic, and leisure activity among older people. Factor analysis identified three main factors, similar in composition to those previously reported. A general linear models regression analysis of selected variables indicated that both fluid intelligence and memory test performance were significantly associated with level of activity. There was no significant association with age or crystallized intelligence in this sample. An apparently strong bias towards higher levels of activity among female respondents was diluted when marital status was included in the equation. This study suggests that the FAI is appropriate for measuring levels of activity in community-dwelling older people and that such activity is related to current cognitive abilities. PMID- 2103571 TI - Hypothyroidism affects reproductive refractoriness and the seasonal oestrous period in Welsh Mountain ewes. AB - Welsh Mountain ewes (n = 6) were rendered hypothyroid by daily treatment with methylthiouracil (35 mg/kg), beginning in early August and ending in late February. Plasma thyroxine levels were reduced by mid-September to about 33% of those in untreated ewes (n = 6). The two groups of ewes were held under natural daylengths until 5 October, then on 12 h light: 12 h darkness (12L:12D) until 28 February when the photoperiod was reduced to 8L:16D. The onset of reproductive cyclicity in October was similar in both groups of ewes but the end of the reproductive period occurred later (P less than 0.05) in the hypothyroid ewes (29 January +/- 7 days (S.E.M.] than in the untreated controls (6 January +/- 7 days). As a result, the duration of the seasonal reproductive period was significantly (P less than 0.05) longer in the hypothyroid (122 +/- 9 days) than in the untreated ewes (91 +/- 10 days). The number of oestrous cycles (duration 15.4 and 15.7 days in the hypothyroid and untreated ewes respectively) was 7.0 +/ 0.6 in the hypothyroid ewes and 5.0 +/- 0.5 (P less than 0.05) in the normal ewes. Reducing the photo-period overcame the reproductive refractoriness and anoestrus in both groups, the hypothyroid ewes beginning to cycle on 13 April (+/ 0.5 days) after an anoestrous period of 72.8 +/- 7.1 days. The untreated ewes began to cycle 2 weeks later on 26 April (+/- 1.7 days) after an anoestrous period of 112.0 +/- 8.5 days (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103572 TI - Possible oncostatic action of cysteamine on the pituitary glands of oestrogen primed hyperprolactinaemic rats. AB - Cysteamine was investigated for its potential to reduce the size and secretion of oestrogen-primed hyperprolactinaemic rat pituitary glands. Subcutaneous administration of 80 and 120 mg cysteamine/kg significantly reduced plasma prolactin concentrations by 58 and 91% respectively, after 4h. Administration of cysteamine (60 mg s.c./kg body weight per day) for 10 days, to rats which had received an injection of 2 mg oestradiol benzoate on day 1, resulted in a significant reduction in pituitary mass (19%) and GH concentration (21%). Oral administration of 60 mg cysteamine/kg body weight to hyperprolactinaemic rats also produced a significant reduction in plasma prolactin of 94% after 2h. Oral administration of 60 mg cysteamine/kg body weight per day to rats for a 20-day period, during which they had received two injections of 2 mg oestradiol benzoate on day 1 and day 14 of treatment, resulted in a significant reduction in pituitary mass (29%) and the concentration of trunk blood prolactin concentration (35%). However, when oral cysteamine (60 mg cysteamine/kg body weight per day) was given for 20 days to rats which had been treated with 2 mg oestradiol benzoate once every 14 days over a 90-day period, it caused no change in pituitary weight, prolactin or GH concentration, or the concentration of prolactin in trunk blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103573 TI - Identification and partial characterization of parathyroid hormone-related protein in human and bovine milk. AB - Parathyroid hormone-related protein (PTHrP) was measured in human and bovine milk by radioimmunoassay (RIA) and bioassay, and the molecular forms characterized by gel chromatography and immunoblotting of affinity-purified PTHrP. Mean immunoreactive PTHrP(1-34) concentrations were 23 and 87 micrograms/l in human and bovine milk respectively. Bioactive (BIO) PTHrP concentrations determined by cyclic AMP production by ROS 17/2.8 cells correlated significantly (P less than 0.001) with those obtained by RIA (BIO = 1.04RIA--3.4, r = 0.939). Gel filtration of human and bovine milk identified several peaks with immunoactivity and bioactivity. Immunoblotting of affinity-purified PTHrP revealed multiple molecular species including components with mobilities similar to those of PTHrP and its subfragments. These studies confirm the presence of immuno- and bioactive PTHrP in milk and suggest that post-translational processing is complex and variable. PMID- 2103574 TI - Aromatase activity in genital skin fibroblasts from normal and androgen insensitive individuals. AB - Human genital skin fibroblasts were used to study aromatase activity by analysing the [3H]H2O released as [1 beta-3H]androstenedione is converted to oestrone. 4 Hydroxyandrostenedione was shown to be a competitive inhibitor of this aromatase activity, the concentration of inhibitor producing 50% inhibition being 1.29 nmol/l. Dexamethasone stimulated the enzyme complex in a dose-dependent manner with half-maximal stimulation at 11.5 nmol/l. A peak of induction occurred after 16 h of preincubation. Measurement of aromatase activity in normal cell strains provided a normal range for the Michaelis-Menten constant (Km) and the maximum velocity (Vmax) of 6.72 +/- 0.54 nmol/l and 215.3 +/- 33.9 fmol/mg protein per h (mean +/- S.E.M., n = 20) respectively. Km values obtained for partial and complete androgen insensitivity syndrome (PAIS and CAIS) patient cell strains were all within the normal range. The mean Vmax +/- S.E.M. in cell strains from patients with PAIS (n = 13) and CAIS (n = 11) were 127.4 +/- 19.2 and 54.8 +/- 19.3 fmol/mg protein per h respectively. Vmax values for patients with CAIS were significantly (P less than 0.001) lower than normal subjects. This suggests that aromatase expression in genital skin fibroblasts is androgen-dependent. PMID- 2103575 TI - Ovine follicular fluid suppresses the ovarian secretion of androgens, oestradiol and inhibin. AB - An experiment was conducted to examine the effect of steroid-free ovine follicular fluid (oFF) on ovarian hormone secretion. Eight Merino x Finnish Landrace ewes in which the left ovary and vascular pedicle had been autotransplanted to a site in the neck were studied during the breeding season. Luteal regression was induced in all animals by injection of cloprostenol (100 micrograms, i.m.) on day 10 of the luteal phase. Four of the eight animals were treated with steroid-free oFF (3 ml, s.c.) in the early follicular phase, 24 and 36 h after injection of cloprostenol. Samples of both ovarian and jugular venous blood were collected at 4-h intervals from 20 h before until 96 h after injection of cloprostenol. Ovarian and jugular venous blood samples were also collected at 10-min intervals from 48 to 52 h after injection of cloprostenol to investigate the pattern of pulsatile secretion of ovarian hormones. Samples were assayed for oestradiol, androstenedione, testosterone and inhibin and the ovarian secretion rates calculated. Both injections of oFF resulted in a fourfold increase in the concentration of inhibin in jugular venous plasma within 4-8 h of administration (P less than 0.01) with concentrations remaining increased (P less than 0.05) until 56 h after cloprostenol (32 h after the first oFF injection). Following oFF injection there was a profound (100%; P less than 0.001) and prolonged decrease in the peripheral concentration of FSH until 60 h after cloprostenol at which time the concentration of FSH increased five- to sixfold (P less than 0.001) to a peak lasting 24 h. In contrast to FSH, the concentration of LH in jugular venous plasma rose immediately following oFF treatment and continued to increase, exhibiting a profile similar to that described for FSH. No preovulatory LH surge was detected in any of the oFF-treated ewes while untreated ewes had an LH surge within 58.0 +/- 1.2 (S.E.M.) h. Within 8 h of the first injection of oFF the ovarian secretion rate of oestradiol, androstenedione and inhibin began to decline to reach a nadir of less than 1 ng/min within 32-36 h (56-60 h after cloprostenol; P less than 0.01). Testosterone secretion, already barely detectable, did not change significantly following injection of oFF but remained low for 36 h following oFF and did not exhibit the increase observed over this period in controls. After injection of oFF the episodic secretion of oestradiol, androstenedione, testosterone and inhibin was markedly suppressed in spite of numerous pulses of LH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2103576 TI - Synthetic parathyroid hormone-related peptide (1-34) fragment stimulates placental calcium transfer in ewes. AB - The influence of synthetic parathyroid hormone related peptide (PTHrp) fragments on placental transfer of Ca was studied in four groups of four single ovine fetuses fitted with catheters chronically implanted into their left jugular vein (for injections) and carotid artery (for blood sampling), and used between days 104 and 118 of gestation. The first group received PTHrp(1-34), the second PTHrp(107-138), the third bovine PTH(1-34), and the last (control) group was injected with solvent alone. Each peptide (6 nmol/fetus per day) was injected i.v. three times per day from day 105 until day 116 of gestation. Placental Ca transfer (mmol/24 h per kg fetal wt) from the dam to the fetus was not different in control fetuses (7.1 +/- 0.6) and those given PTHrp(107-138) (7.2 +/- 0.5), but it was significantly increased by bovine PTH(1-34) (8.6 +/- 0.4; P less than 0.05) and by PTHrp(1-34) (10.1 +/- 0.3; P less than 0.01). Both peptides also significantly increased plasma concentrations of 1,25 dihydroxy-vitamin D3 (1,25 (OH)2D). These results indicate that PTHrp(1-34) can stimulate placental Ca transfer by increasing 1,25-(OH)2D synthesis, but also possibly by acting directly upon the placenta. PMID- 2103577 TI - Paracrine control of anterior pituitary hormone secretion. PMID- 2103578 TI - N-acetyltransferase activity in the Harderian glands of the Syrian hamster, Mesocricetus auratus, is regulated by androgens and by hormones of the pituitary thyroid axis. AB - This study tested the hypothesis that activity of the enzyme N-acetyltransferase (NAT) in the Harderian gland of the Syrian hamster is regulated both by androgens and by hormones of the pituitary-thyroid axis. To test the effects of castration and hypothyroidism, intact or castrated male hamsters were given either tap water or methimazole in their drinking water for 3 weeks. Methimazole suppresses iodination of thyroglobulin, thereby decreasing circulating levels of thyroid hormones and increasing TSH levels. Hypothyroidism or castration caused elevated or depressed Harderian gland NAT activities respectively, compared with euthyroid controls. When castration and hypothyroidism were combined, the animals exhibited high NAT activity compared with castrated euthyroid males. To test the effects of castration and hyperthyroidism, male hamsters were given daily injections of thyroxine (T4) or diluent and were either castrated or left intact for 4 weeks. Intact animals given T4 had depressed Harderian NAT activity; serum thyroid hormone levels were elevated and TSH levels were depressed compared with those of intact controls. Castrated animals had depressed NAT activity below that of intact controls; serum thyroid hormone levels were normal but TSH levels were depressed. Castrated animals given T4 injections had NAT activity similar to that of euthyroid castrated hamsters; thyroid hormone levels were elevated but TSH levels were similar to those seen in euthyroid castrated hamsters. In another experiment, both T4 and tri-iodothyronine (T3) were equally effective in decreasing NAT activity in intact males. To determine the effects of the removal of pituitary influences, male hamsters were hypophysectomized. NAT activity in the Harderian glands of these animals was reduced compared with intact controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103579 TI - Burrhus Frederic Skinner (1904-1990) (a thank-you). PMID- 2103580 TI - The utility of verbal and behavioral assessments of value. AB - Subjects lived in a laboratory apartment for up to 30 days, engaging in ordinary activities such as reading, sewing, and artwork. The amount of time devoted to each activity was recorded and compared with periodic verbal ratings of the amount of time devoted to the activities. The verbal and observational assessments of the time distribution were very similar, but there were some discrepancies. Based on self-reports and on observation of time actually devoted to the activities, contingencies were arranged in which time devoted to one activity produced time available for a second activity. When the contingency relation was based on behavioral assessment, predictions of time redistribution were more accurate than when the relations were based on verbal assessment. The close correspondence between observed distributions of time and verbally assessed distributions was probably due to the well-specified situation and rigorous assessment methods. Contrary to some cognitive-behavioral accounts, the contingency results suggest that verbal assessment is not necessarily preferable to observation when the two make discrepant predictions. It is suggested that verbal reports might be used more often in behavior analysis in place of lengthy or difficult observations, and attention is drawn to a personality model that parallels important components of behavior analysis. PMID- 2103581 TI - Observing behavior in a computer game. AB - Contingencies studied in lever-pressing procedures were incorporated into a popular computer game, "Star Trek," played by college students. One putative reinforcer, the opportunity to destroy Klingon invaders, was scheduled independently of responding according to a variable-time schedule that alternated unpredictably with equal periods of Klingon unavailability (mixed variable time, extinction schedule of reinforcement). Two commands ("observing responses") each produced stimuli that were either correlated or uncorrelated with the two components. In several variations of the basic game, an S-, or bad news, was not as reinforcing as an S+, or good news. In addition, in other conditions for the same subjects observing responses were not maintained better by bad news than by an uninformative stimulus. In both choices, more observing tended to be maintained by an S- for response-independent Klingons when its information could be (and was) used to advantage with respect to other types of reinforcement in the situation (Parts 1 and 2) than when the information could not be so used (Part 3). The findings favor the conditioned reinforcement hypothesis of observing behavior over the uncertainty-reduction hypothesis. This extends research to a more natural setting and to multialternative concurrent schedules of events of seemingly intrinsic value. PMID- 2103582 TI - Recognition memory in older adults: adjustment to changing contingencies. AB - Four older and 4 younger men were given extended exposure to a continuous recognition memory procedure. Experimental variables included the type of stimulus (alphanumeric strings, words, or sentences), the intervals separating repeated items, gains and losses for correct and incorrect recognitions, and the extent of practice with the memory task. Signal detection analyses indicated that the older men generally were less accurate (sensitivity), particularly when the stimuli were strings, but that age differences decreased with practice. Under conditions in which the payoff matrix was neutral, the older and younger men showed equivalent rates of hits and false alarms (bias). Alteration of the matrix to require more liberal or more conservative patterns of recognition responding led to corresponding changes for men of both ages. Adjustments by the older men, however, were not as close to the bias values called for by the new matrices. PMID- 2103583 TI - Development of conditional and equivalence relations without differential consequences. AB - Two experiments were conducted to establish conditional stimulus relations without differential consequences and to test for the emergence of other relations. In Experiment 1, 3 adults responded to match-to-sample displays in which sample-comparison pairs were constant while the second comparison presented with each pair changed periodically across trials. No differential consequences followed any comparison selections. All subjects learned conditional relations between constant samples and comparisons, but results of tests for transitivity in those relations were equivocal. In Experiment 2, 4 children were given unreinforced training and testing similar to that provided to the adults in Experiment 1, with procedural refinements. One child learned conditional relations and demonstrated emergent relations that confirmed the development of two four-member equivalence classes. Another child learned the conditional relations but did not demonstrate any emergent relations reliably. A 3rd child, after reinforced training on two conditional relations, learned four new conditional relations without differential consequences and demonstrated symmetry but not equivalence in the trained relations. The 4th child did not learn the conditional relations. These findings emphasize the importance of careful construction of tests for stimulus equivalence and suggest a need for critical analyses of the apparent emergence of untrained stimulus relations on unreinforced tests that has been observed in several stimulus equivalence studies. PMID- 2103584 TI - Conditional discrimination in mentally retarded adults: the development of generalized skills. AB - The development of generalized conditional discrimination skills was examined in adults with retardation. Two subjects with histories of failure to acquire arbitrary matching under trial-and-error procedures were successful under procedures that trained one or more prerequisite skills. The successive discrimination between the sample stimuli was established by training the subjects to name the stimuli. The simultaneous discrimination between the comparison stimuli was established using either (a) standard simple discrimination training with reversals or (b) a procedure in which each of the two sample-comparison relations in the conditional discrimination was presented in blocks of trials, with the size of the blocks decreasing gradually until sample presentation was randomized. The amount of prerequisite training required varied across subjects and across successive conditional discriminations. After acquiring either two or three conditional discriminations with component training, both subjects learned new conditional discriminations under trial-and error procedures. In general, each successive conditional discrimination was acquired more rapidly. Tests showed that conditional responding had become a generalized skill. Symmetry was shown for almost all trained relations. Symmetry trial samples were ultimately named the same as the stimuli to which they were related in training. PMID- 2103585 TI - Skinner's verbal behavior, Chomsky's review, and mentalism. AB - Skinner's Verbal Behavior (1957) is a comprehensive treatise that deals with most aspects of verbal behavior. However, its treatment of the learning of grammatical behavior has been challenged repeatedly (e.g., Chomsky, 1959). The present paper will attempt to show that the learning of grammar and syntax can be dealt with adequately within a behavior-analytic framework. There is no need to adopt mentalist (or cognitivist) positions or to add mentalist elements to behaviorist theories. PMID- 2103586 TI - Cognition and behavior analysis: a review of Rachlin's judgment, decision, and choice. PMID- 2103587 TI - [Regional meetings of the Japanese Circulation Society. 1988-1989. Abstracts]. PMID- 2103588 TI - Cutaneous sporotrichosis in Thailand: first reported case. AB - A case of cutaneous sporotrichosis is reported for the first time in Thailand. The infection occurred in a 33-year-old Thai female who has been in good health and had no history of previous trauma or contact with any animals. Histopathology revealed pseudoepitheliomatous hyperplasia of the epidermis and a combination of granulomatous and pyogenic reactions in the dermis and subcutaneous tissue. Typical asteroid bodies (Splendore-Hoeppli phenomenon) with central yeast cells were seen. Sporothrix schenckii was recovered from skin biopsy specimens. The patient responded well to the treatment with saturated solutions of potassium iodide within three months. No recurrence was seen after more than six months follow-up. PMID- 2103589 TI - Indirect immunofluorescence staining and crossed immunoelectrophoresis for differentiation of Candida albicans and Geotrichum candidum. AB - Rabbit hyperimmune antisera were used for differential diagnosis of Candida albicans and Geotrichum candidum in murine and bovine tissues by indirect immunofluorescence (IIF) staining. Although the antisera did not detect common antigens by crossed immunoelectrophoresis (XIE) a marked cross-reactivity of fungal cells was observed in the IIF assay. Following liquid phase absorption with heterologous antigenic preparations the hyperimmune antisera were rendered specific for each species thus making possible an unequivocal differentiation of the two species. PMID- 2103590 TI - Biotyping of Candida strains with regard to the epidemiology of candidosis. A practical approach. AB - In 62 strains of Candida albicans cultivated from specimens of patients with recurrent vaginal candidosis or with renal transplants, the biotypes were determined according to several characters: colony morphology, production of chlamydospores, auxanogram of C- and N-substances, zymogram, growth kinetics, adherence capability, proteolytic activity, sensitivity to 6 antimycotics, and serotypes. On the basis of this typing system the endogenous and exogenous sources of chronic vaginal candidosis as well as the sources of systemic candidosis in patients with renal transplants could be evaluated. PMID- 2103591 TI - Malassezia furfur colonization of neonates in an intensive care unit. AB - We studied Malassezia furfur colonization of neonates in the neonatal intensive care unit (NICU) and found that the rate was astonishingly high as compared to the previous studies. In very low birth weight (less than 1,000 g) infants we recorded a colonization rate of 80%, and 4% infants with a birth weight greater than 2,000 g. Under 10 day's hospitalization the rate was 11%, and it was 70% after 20 days spent in the unit. Among the infants with the birth weight less than 1,700 g, antibiotic therapy was recorded as a significant risk factor for colonization. In the infants with a greater birth weight, the colonization rate was independent from the risk factors studied. M. furfur colonization could not be linked with occurrence of any symptoms of signs recorded and colonization by M. furfur was so common in NICU that the predictive value of surveillance cultures is poor. PMID- 2103592 TI - Pityriasis versicolor in school children in Cross River State of Nigeria. AB - Out of 2,353 primary school children aged 4-16 years in Cross River State of Nigeria examined, 88 (3.7%) showed lesions mycologically proven to be pityriasis versicolor. Incidence was highest (6.3%) in children aged 12-16. Lesions were much more common on the face than on other sites. PMID- 2103593 TI - In vitro nail invasion by pathogenic and non-pathogenic fungi under different culture conditions. AB - Data from the literature suggest that the nutritional environment can modify major metabolic functions of fungi and possibly their aggressivity towards keratinous structures. Trichophyton rubrum (TR), Microsporum canis (MC), Scopulariopsis brevicaulis (SB), Aspergillus fumigatus (AF) and Penicillium spec. (P) were inoculated on media of different nutritional value, in presence of nail fragments. The activity of the fungi was evaluated at two and four weeks for intensity and depth of invasion of nail samples. Nail invasion was most pronounced by MC, especially when grown on rice agar or peptone agar. Nail invasion by the other fungi tested was less important, Sabourand glucose and rice agar were most favorable. Our results indicate that nutritional factors can, at least in some fungus species, alter their rate of nail invasion. PMID- 2103594 TI - Pathogenicity of Trichosporon capitatum for normal and irradiated mice and the efficacy of miconazole on experimental systemic trichosporosis in mice. AB - The authors describe the course of experimental trichosporosis in normal and X irradiated ICR mice after i.v. inoculation with Trichosporon capitatum. The irradiated animals were considerably more sensitive to infection than normal animals. The LD50 challenge dose used was by approximately two orders lower (1 X 10(3) c.f.u. ml-1) in irradiated mice than in control animals. The histopathological examination of the internal organs of the infected mice demonstrated that the greatest tissue damage was associated with the kidneys, liver and spleen. However, the infectious agent was also found in heart, lungs and brain. The degree of impairment of the tissues was dependent on the inoculation dose and on the irradiation status. Miconazole (50 mg kg-1) was administered i.p. immediately after inoculation with Ts. capitatum and resulted in an alteration of infection and prolonged survival time. Miconazole was ineffective when challenge dose were used which produced 100% mortality (1 X 10(6) and 1 X 10(4) c.f.u. ml-1 for normal and irradiated mice, respectively). With the use of these doses also the course of infection was nearly identical both in the miconazole-treated and untreated animals. PMID- 2103595 TI - Clotrimazole and bifonazole in the topical treatment of Candida keratitis in rabbits. AB - Using a reproducible model of Candida albicans keratitis in rabbits we studied the effect of topical clotrimazole and bifonazole. Candida albicans DSM 70010 (2.5 X 10(5) cells) was injected into the corneal stroma of both eyes of 28 rabbits. All eyes developed a corneal ulcer. Fourty-eight hours after inoculation the animals were divided into four groups: I (14 eyes) receiving 10 X clotrimazole 1% drops and subsequently removing the epithelium; II (14 eyes) receiving only clotrimazole drops; III (8 eyes) receiving 6 x bifonazole 1% drops and IV (19 eyes) serving as control (0.9% NaCl castor oil, untreated), 6 eyes of this group were also debrided. A further 6 rabbits were used respectively to judge if the drugs penetrated into the cornea and aqueous humor. There was a significant difference between the clotrimazole group with debridement (I) and the bifonazole group (IV) concerning hypopyon and complications (descemetocele, corneal perforation). Clotrimazole penetrated into the cornea and after debridement into the aqueous humor. Bifonazole could not be identified in the cornea or aqueous humor. PMID- 2103596 TI - Systematic control of dermatophytosis profunda of cattle in the former GDR. AB - Human occupational diseases orginated from Trichophyton verrucosum infection of cattle belonged to the most frequent zooanthroponoses since 1960. Morbidity peaks of this human dermatophytosis could be observed in 1970 and 1971 with about 740 cases of occupational diseases per year. The ecological properties of Tr. verrucosum (compulsory monoxenic parasite), the pathogenetic development of bovine dermatophytosis (rising immunity with subsequent elimination of the agent), systematic medical therapy and prophylaxis with griseofulvin and other drugs as well as the application of Tr. verrucosum live vaccines were the preconditions for a successful control of this zooanthroponosis. Since then the number of human and animal diseases could be essentially reduced. PMID- 2103597 TI - Dermatomycoses and their etiology in the material of the Dermatological Department in Lodz, Poland. AB - In the period of 1982-1988 mycological examinations were carried out on 4,657 patients suspected of having dermatomycoses. In approximately 60% of patients infections were localized on the feet and hands and in approximately 30% other regions of the glabrous skin were involved. Before treatment, 5,725 examinations were made. The diagnosis was confirmed mycologically in 30% of the cases, most often in tinea cruris (51%) and chronic paronychia (60%). In more than half of the cases the isolated fungi were dermatophytes, the most frequent species being Tr. mentagrophytes, followed by Tr. rubrum and E. floccosum. Among the other fungi, more than 50% were C. albicans and other Candida species. PMID- 2103598 TI - [Fluoride ions and apatite recrystallization of apatite in enamel]. AB - The authors discuss the basic process on which the principle of fluoridation in based--i.e. the mutual exchange of F- ions and the OH- group in hydroxyapatite of enamel. Model investigations assessing the energy difference between hydroxyapatite and F- and fluorapatite and the OH- group indicate that fluorapatite tends to release steadily fluoride ions and to change into hydroxyapatite. This tendency, apparently inopportune from the aspects of caries prevention, ensures, however, a permanent low F- level above the enamel surface. The presence of F- ions facilitates recrystalization of apatite in the initial caries stage. The investigation tries to throw new light, from the point of view of theoretical chemistry at a molecular level, on the mechanism of remineralization, one of the most important ways which implements the preventive action of fluoride. PMID- 2103599 TI - [Comments on the preparation of pillar teeth]. AB - The author draws attention to some short comings of contemporary advice regarding the preparation of pillar teeth, in particular as regards the relationship of their longitudinal axes and corresponding surfaces. The author indicates possibilities sparing preparation and the test its importance experimentally with regard to sparing of hard dental tissues. PMID- 2103600 TI - [Contribution of the treatment of discoloured teeth]. AB - New dental materials and their combinations increase the aesthetic and functional quality of treatment. A great improvement in the aesthetic treatment of discoloured teeth is the use of dental ceramic combined with composites. PMID- 2103601 TI - [Sutures of wounds after surgery of the periodontium. 2. The suture in operation with listing of the mucoperiosteal flaps]. PMID- 2103602 TI - [Comparative study of the prevalence of disorders of impaired structure of dental tissues in school children and university students]. AB - The authors examined a group of 573 Prague children aged 12-15 years. In addition to the incidence of disorders of the structure of dental tissues they investigated the coriosity (DPE), oral hygiene (OHI) and condition of the gingiva (PI). Their main interest was focused on impaired mineralization of dental tissues the incidence of which is indemic in Prague children. The group was compared with 62 university students. It is of interest that in all indicator except impaired mineralization, the children had significantly better results. The rising curve of impaired mineralization signalises the ever deteriorating living environment in the capital. PMID- 2103603 TI - [Amalgam filling in clinical practice]. AB - The quality of treatment of dental defects with amalgam is closely associated with the preparation of the cavity and its filling as well as with completion of the filling and its finish. Strict adherence of a correct working procedure improves markedly the standard of treatment and makes it possible to make use of the positive properties of amalgam from which the filling is prepared. PMID- 2103604 TI - [The effectiveness of psychotherapeutic methods in paedodontics]. AB - The authors divide psychotherapeutis procedures and method influencing the patient's behavior during dental treatment into preventive methods and those facilitating treatment and making treatment possible. At the same time they evaluate their effectiveness in a group of 269 "untreatable patients" with a different intellectual level. They found that these methods were successful in almost half the patients when treating preschool and primary school children. PMID- 2103605 TI - [Expansion of a lower shallow vestibule by Schmid and Mormann's operation]. AB - In the introduction the authors give a brief account of the development of different methods used for correction of a low, shallow vestibule by Schmid and Mormann's operation which is a modification of Edlan and Mejchar's method. With regard to the favourable results obtained with this operation so far, the authors recommended its wider use. PMID- 2103606 TI - [Effect of water on the binding firmness of construction materials in fixed aesthetic prostheses]. AB - The authors investigated the problem of the effect of a damp environment on the mechanical properties of aesthetic materials used for fixed prostheses (top lacques Conalor and polymethylmetacrylate resin Superpont C and B). For tests they used bodies made from chromium cobalt alloy with two types of retention--R polymer and loop. In the combination metal-resin the differences of values are significant, when the top lacquer Conalor is used, the changes of values are not so maded to be statistically significant. A traction test of bodies prepared from Superpont C + B wal also to assess the range of firmness in relation to the period of storage in distilled water. The authors found an increase of the range of firmness within one week and a marked decline after two weeks. The performed tests provided evidence of a rise of the binding firmness due to the absorption by the resin, and confirmed the stabilized behaviour of the lacquer Conalor. PMID- 2103607 TI - [Epidemiological investigation of oral health in a group of Prague University students]. AB - In the submitted paper the authors investigated the state of teeth, periodontium and the need of treatment in a group of Prague university students. In the investigated group they recorder a lower cariosity than in the same age group 30 years ago. The percentage of subjects without dental extraction on account of caries is smaller than foreseen by WHO in the year 2000. Both is evidence of early therapeutic and preventive care in previous years. To maintain therapeutic and preventive care in previous years. To maintain the positive results of systematic dental care, regular dental treatment also in adult age is essential. PMID- 2103608 TI - [Knowledge of sixteen-year-olds of oral hygiene]. AB - Consistent with the declaration of WHO "Health for all by the year 2000" and the FDI programme "Oral Health by the year 2000" the aim of our work was to become familiar with habits and knowledge on oral hygiene in 16-year-old adolescents. In 1988 we examined a total of 180 adolescents selected at random in one Prague secondary school and two centres for apprentices. For the assessment of habits regarding oral hygiene and knowledge on oral hygiene we used own questionnaire comprising 33 questions. The investigation provides evidence that it is essential to motivate patients more effectively to improve oral hygiene and to instruct during dental examinations on the importance of proper dental care. Dental surgeons should use every visit of the patient to explain oral hygiene and check adherence to it. PMID- 2103609 TI - [Viral hepatitis type B and its possible prevention by vaccination]. PMID- 2103610 TI - [Chronic candidosis]. AB - The paper deals with the problem of mucocutaneous candidosis, because the incidence of the disease is increasing steadily in recent years. The author draws attention to various already known causes of the development of candidosis and submits also some hypothese reported in the literature. The classification of candidosis should facilitate diagnostic work of the attending physician. In therapy in particularly refractory candidoses are emphasized and the author present on the example of one patient an account of recent therapeutic possibilities. PMID- 2103611 TI - [Electric socket for heating dentiplast]. PMID- 2103612 TI - [Partial results of an investigation of the state of dentition of the Czechoslovak population with regard to targets of WHO for the year 2000]. AB - In 1987 a nation-wide survey of the state of dentition of Czechoslovak population in age groups of 2-65 years and above was made. The paper presents the results in the age category of 5-6 years, 12 years, 18 years, 35-44 and 65 year and more, with regard to criteria defined for WHO targets for the year 2000. Data for the CSSR, SSR and CSSR are presented separately. PMID- 2103613 TI - [Anamnestic incidence of hepatitis B in the population of Prague stomatologists]. AB - The author assessed by means of questionnaires the incidence of hepatitis B and the use of protective devices in a group of 612 Prague stomatologists. Fifty-four (3.8%) reported hepatitis B. 17.5% of the doctors were vaccinated against the condition. Doctors who treat 20 or more patients per day report hepatitis B four times more frequently than those who treat only to 20 patients per day. 53.5% of the doctors never use rubber gloves during treatment. For the prevention of transmission of infection in addition to hygienic provisions also the organization of work must be changed. PMID- 2103614 TI - [Reasons for extraction of permanent teeth in a health community dental centre]. AB - The authors assessed the diagnostic reasons for extraction of 1170 teeth in 565 patients treated in a health community dental centre. They recorded data on the patient's sex and age, on the extracted tooth and reason for extraction. They found that under the age of 30 years permanent teeth were extracter mostly on account of extensive damage by caries and its sequelae. On account of destruction of the periodontium permanent teeth were extracted in patients older than 31 years. At the age of 31-40 years on account of extensive caries and its complications significantly more teeth were extracted in women than in men, at the age above 71 years significantly more teeth were extracted on account of this diagnosis in men, as compared with women. On account of caries and its sequelae 75.7% upper premolars, 69.7% upper molars and 69.9% lower molars were extracted. On account of advanced destruction of the periodontium in the investigated group 80.5% lower incisors were extracted. In other groups of teeth this diagnosis was less frequent. PMID- 2103615 TI - [Hemiextraction--use of less common pillars in prosthetics]. PMID- 2103616 TI - [Treatment of dysfunction of the temporomandibular joint by an occlusion splint]. AB - At present we include under the term arthropathy of the temporomandibular joint a large group of affections of this joint. In recent years the term myofacial painful dysfunction syndrome was defined in mode detail. It is a condition characterized by its polyaetiological nature and is linked to the area of the temporo-mandibular joint and its surroundings. It is associated with pain without apparent destructive changes on the X-ray picture. In the submitted paper attention is paid to conservative treatment of painful dysfunctional muscular syndrome by means of an occulsion splint. In a group of 32 patient the advantages of the method are demonstrated. PMID- 2103617 TI - [Multi-purpose tripod for photodocumentation in stomatology]. PMID- 2103618 TI - [Antimicrobial action of a repin bandage in periodontology]. AB - The paper deals with the antimicrobial activity of repin bandages used commonly in periodontology. The main criterium for evaluation was the number of bacteria in the wound beneath the bandage, ass ossessed by cultivation. The authors compared three types of bandages (Repin with Traumacel, Repin with Framykoin and Repin alone). Repin with Framykoin reduced most effectively the number of micro organisms for the longest period of time. The results revealed that the amount of bacteriabacteria beneath the bandage is proportional to the period of time for which the bandage is left in the oral cavity. The optimal period is five days. PMID- 2103619 TI - [Treatment of defects of the cervical portion by a "sandwich" filling]. AB - The authors draw attention to some peculiarities of treatment of class V cavities by aesthetic fillings. Combined filling made from silicocarboxyl cement and composite filling material prove useful. In teeth with preserved pulp sandwich fillings are used which contain three layers (base, intermediate retention layer of silicocarboxyl cement and composite material). In pulpless teeth, the base is not needed and the term combined filling (two layers) is more appropriate. PMID- 2103620 TI - [Koferdam and its application]. AB - For perfect dental treatment it is essential in the majority of cases to ensure a readily surveyed and perfectly dry working field. This is met best by the use of the rubber membrane--koferdam. In the submitted work the authors inform the stomatological public on basic terms and principles of work with koferdam which is considered irreplaceable under certain conditions. PMID- 2103621 TI - [Problems of adolescent dental care on the background of paedostomatological care]. PMID- 2103622 TI - [New aspects of pharmacotherapy of pain with regard to stomatology. 2]. PMID- 2103623 TI - [Acupuncture in stomatology]. AB - The authors draws attention to the possible use of acupuncture in stomatology used in the course of 13 years in diseases of polyaetiological nature or where the aetiology is not well known. They demonstrate the success of this therapeutic method in diseases such as glossodynia, stomatodynia, primary neuralgia of the trigreminal nerve, contractures of the jaws, myofacial dysfunctional syndrome and disorders of salivary secretion in 178 patients treated at the out-patient department of the Second Stomatological Clinic in Bratislava. PMID- 2103624 TI - [Possibilities of dental compensation of skeletal orthodontic defects in relation to aesthetic aspects of the lips]. AB - The author describes a practical method of reconstruction of the position of the incisors and its influence on aesthetic aspects of the lips in patients treated on account of serious orthodontic defects. Before treatment is started it is necessary to analyze the condition of the dentition and the patient's profile. When selection the therapeutic plan, we have to determine the future position of the incisors and predict the influence of the new position of the incisors on the patient's profile. The author describes the procedure during reconstruction of the position of the incisors and the mutual position of the lips. Without prediction of changes of the profile it is not possible to predict whether orthodontic treatment will not cause deterioration of the patient's profile. PMID- 2103625 TI - [Contribution to the treatment of children in the first aid medical service of the stomatological department]. AB - At the first aid medical service of the stomatological department of a type II hospital with policlinic in the course of the calendar year a total of 1,761 children from 2-15 years were treated. During this period the staff treater 1,718 teeth and 43 times they treater soft tissues of the oral cavity. Most frequently periodontitis of the decidual teeth was treated, resorption of the root of a decidual tooth, pulpitis and caries. As to therapy, extractions were most frequent, followed by trepanation of the pulp cavity and treatment of the tooth by a provisional filling. The author draws attention to unsuitable therapeutic procedures such as trepanation of the pulp cavity in case of periodonititis of a decidual tooth and application of cobalt in pulpitis of a decidual tooth after the age of seven years. She emphasizes also the necessity to use local anaesthesia in extraction of decidual teeth. PMID- 2103626 TI - [Cariosity in adolescents]. AB - The authors give an account of the results of an epidemilogical investigation of the cariosity in adolescents of the East Slovakia region. They assessed the prevalence of caries and the intensity of cariosity by means of the DMF index. They investigated also the cariosity of individual teeth and the cariosity in individual subjects. The incidence of dental caries is 98.7% and the intensity according to the DMF index is on average 8.9. PMID- 2103627 TI - [Periodontopathies and fixed prosthetic appliances]. AB - The authors examined a group of 979 subjects with fixed prosthetic appliances, admitted for treatment at the periodontological department on account of periodontopathy. The group was subdivided according to sex, age, periodontological diagnosis and type of fixed prosthetic appliance. Based on the results of the initial examination, the authors compared the state of the periodontium of teeth with a prosthetic appliance and the other teeth using Russell's clinical and X-ray PI index. They investigated the oral cavity, using the OHI-S index according to Green and Vermillion and the DMF index. The results confirmed the negative influence of fixed prosthetic appliances on the periodontium and revealed the necessity of X-ray check-ups of the periodontium of teeth white these appliances. PMID- 2103628 TI - [Condition of the teeth and oral hygiene in medical students, stomatological branch, Palacky University Olomouc]. AB - The paper deals with assessment of the cariosity of teeth, hygiene of the oral cavity, needs and quality of treatment in 126 dental medical students, Palacky University, Olomouc in the school year 1987/88. From the assembled results it may be concluded that the health consciousness of care of oral health even in groups of interested persons, as we may anticipate in dental the students is not reflected in their attitude to their own health. This is the more problematical as it may make us think that health education is not a sufficient impulse for medical students. PMID- 2103629 TI - [Influence of the height of the occlusion splint in the treatment of dysfunctional articular syndrome]. AB - The authors subjected 30 patients of both sexes aged on average 35.5 years with dysfunctional syndrome of the mandibular joint to clinical and X-ray examination. As monotherapy they used a temporary occlusion splint made from resin with a vertical dimension of 2, 4 and 6 mm and investigated its effect on the regression of complaints. The best therapeutic effect and most rapid regression of complaints was recorded in the group of patients with a 6 mm spleen. PMID- 2103630 TI - [Possibilities of treatment of reversed occlusions by removable devices. Indications for treatment with removable devices according to teleroentgenograms]. AB - The author used as a basis Jarabak's classification class III. She assessed the skeletal parameters which are important for elaboration of the therapeutic plan, for assessment of therapeutic possibilities by means of a removable device or the necessity of treatment by means of a fixed device. During analysis of the teleroentgenogram she considers it most important for the treatment by means of removable devices to assess in addition to the extent of the defect the following parameters: 1. the angle of the sella 2. the length of the body of the lower jaw 3. the inclination of the upper incisors 4. the inclination of the lower incisors PMID- 2103631 TI - [Diagnostic method for assessment of possible distalization of the first upper molars]. AB - The therapeutic method of distalization of the first upper molars by external traction has been considerably extended in recent years. Some failures are, however, encountered. The cause is lack of space. The author elaborated a method which helps to assess the future spatial possibilities in the molar region. The distance between the distal margin of the first upper molar from the normal from the posterior margin of the maxilla on the bispinal plane is assesed: +6:M. Point "M" is the most posterior point on the anterior border of the fissura pterygopalatina. At the same time the breadth of the second and third molar is taken into account where considerable individual differences exist. The growth of the maxilla in the molar region was investigated in a group of 146 probands. Growth increments, on average 1 mm per year, were recorded up to the age of 18 years. Based on this information the author elaborated a formula for assessment of possible distalization of the molars: M2 + M3 + PP = + 6:M + (age 18-of the patient). The sum of the width of the crowns of the second molar (M2) and third molar (M3) and the planned distal shift of the first molar (PP) equals distance + 6 from the normal from point M on the bispinal plane (+6:M) plus the difference between 18 and the patient's age. PMID- 2103633 TI - [Complicated extraction of a second upper molar]. PMID- 2103632 TI - [Incidence of maxillary orthopaedic anomalies in adolescents]. AB - Within the framework of an epidemiological survey of the state of dentition the authors examined some 4% of adolescents in the East Slovakian region (aged 15-18 years). The authors recorded the following values according to Angle's classification: A II/1-14.3% A II/2-7.5% A III-3.1%. Abnormal position of the frontal teeth: retrusion-8.2% protrusion-12.2% cramming-19.7%. Incidence of malocclusion: deep occlusion-23.8% labial occlusion-4.4% open occlusion-5.8% crossed occlusion-7.3%. Diastema with normal position of the frontal teeth-7.9%. The authors evaluate the total incidence of maxillary orthopaedic defects-70.2% as very high. PMID- 2103634 TI - [Validation and environmental control of preparation operations. Fifth communication of the Comite des Laboratoires et Services Officiels de Controle des Medicaments et de la Section des Pharmaciens de l'Industrie'-F.I.P, May 1990]. AB - The many different check-points concerning the complementary activities of validation and monitoring of aseptically processed pharmaceutical preparations are described. The features are based on the official and current GMP guidelines. These are outlined in practical terms according to the personal experience of the authors and manufacturing specialists who were consulted. PMID- 2103635 TI - The isolated perfused heart according to Langendorff technique--function- application. AB - 1. Definition. The isolated perfused heart according to Langendorff is a preparation which is easily obtained from all warm-blooded animals. The heart is usually perfused at constant pressure, but frequently at constant flow, mostly with oxygenated saline solutions. The ventricles do not fill with the perfusate and therefore do not perform pressure-volume work. If, however, an intraventricular balloon is inserted, the ventricle can contract isovolumetrically. 2. Measuring parameters. Mechanical parameters of the working myocardium (contractile force, volume, ventricular diameter), mean coronary flow, bioelectrical parameters (EKG, monophasic injury potentials), and cardiac rhythm can be measured and recorded. 3. Function tests. The intact function of the working myocardium and the coronary vessels should be examined using various simple tests regarding the myocardium, the smooth musculature, and the endothelium of coronary vessels. 4. Possible applications. In the Langendorff heart of normal or pretreated animals, inotropic, chronotropic, antiarrhythmic or vasoactive substances can be investigated in the steady state or by means of specific stress tests. In addition, the preparation is particularly suitable for biochemical studies of myocardial metabolism. 6. Advantages. Due to the technical ease with which a variety of parameters can be measured, a single heart can provide maximum information about the condition of the myocardium and the coronary vessels. Thus, it is not surprising to find that 90 years after its first description, the isolated perfused heart according to Langendorff continues to be utilized. PMID- 2103636 TI - Nucleoli in the cells of the erythrocyte and granulocyte series in the albino rat. AB - In albino rats, as in other mammals, nucleoli with nucleolonemata and compact nucleoli in the stem cells of the erythrocyte and granulocyte series are progressively replaced during maturation and differentiation first by ring shaped nucleoli and then by micronucleoli with low and finally with inhibited RNA synthesis. There are, however, differences between the nucleolar coefficient values and the proportion of ring shaped nucleoli and micronucleoli in maturing neutrophils in the albino rat, the mouse and man. In the case of the erythroblasts, the differences between the proportion of various nucleolar types in the three given species are smaller. The results thus indicate that the developmental trend of nucleolar changes related to cell maturation and differentiation is the same, but that there are interspecies differences because of which the results obtained in one species cannot be applied mechanically to another, i.e. results obtained in a laboratory animal cannot be applied automatically to man. PMID- 2103637 TI - Time course of lipid peroxidation during incomplete ischaemia followed by reperfusion in rat brain. AB - The time course of lipid peroxidation was studied in the rat brain cortex after ischaemia and reperfusion. The ischaemia was induced by 4-hour occlusion of both common carotid arteries and was followed by reperfusion of different duration (10, 30 or 60 min). The extent of lipid peroxidation was determined by measurement of conjugated dienes (CD) and TBA reactive products. Maximal values of CD and TBA reactive products were found after 10- and 30-minute reperfusion. This indicated the most suitable time interval for studying the effect of antioxidants and oxygen radical scavengers in this model of brain ischaemia. PMID- 2103638 TI - Amino acid (GAS:BCAA) ratios in plasma and gut contents of short-term protein depleted rats. AB - The ratio of total concentrations or molar ratios (moles/1,000 amino acid residues) of three non-essential amino acids (glycine, alanine, serine-GAS) and three essential-branched chain amino acids (valine, isoleucine, leucine-BCAA) were investigated in rat systemic and portal vein plasma and jejunal and ileal gut contents after feeding normoprotein (NP) or protein-free (PF) diets for 7 days. Amino acid analysis of gut content showed that the GAS:BCAA ratio was not significantly altered by the PF diet either in the jejunum or in the ileum. On the contrary, the PF diet, caused a three and four-fold increase in this ratio in the portal and systemic plasma, respectively. The situation was produced by the higher concentrations of GAS, which remained near control levels (portal plasma) or exceeded these values (systemic plasma), in contrast to the decreasing levels of BCAA found in both plasmas of the PF group. PMID- 2103639 TI - [Bacteriological detection of crude oil contamination in the Bahia Blanca estuary]. AB - In order to evaluate the distribution of occasional oil spills produced by floating system for transferring crude oil, the number of hydrocarbon-degrading bacteria was counted in superficial sediments from Bahia Blanca Estuary, using the Most Probable Number method. Sediment were collected from ten stations located between buoys 21 and 16. Heterotrophic aerobic marine bacteria were counted on Marine Agar 2216. Determination of organic carbon was also carried out. On the base of the number of hydrocarbon-degrading bacteria, statistical analysis differentiated two zones with different degree of pollution, one including the stations of the Principal Channel, with average values, expressed as log10, which ranged from 2.98 to 3.65 bacteria/g of dry sediment, and the other from 4.16 to 4.37, located in small channels on the Southern coast. These results suggest a drift of the oil perpendicular to the Principal Channel, probably caused by the action of predominant winds with direction N, NNW. A linear regression analysis determined highly significant relationship between organic carbon and both bacterial groups. This study shows that the spilled oil is affecting productive zones of the estuary. PMID- 2103640 TI - [Mycotoxins of Fusarium spp. in rotten fruits from Cucurbita ficifolia]. AB - Swine acute toxicosis with hemorrhages was recognized after feeding on decayed chayotes (C. ficifolia fruits). In order to elucidate the origin of this pathology, chayotes spoiled by fusaria were analyzed. The mycotoxins (T-2 toxin, fusarenon X) identified in decayed chayotes, the mice alterations and the isolated species (F. equiseli, F. graminearum, F. heterosporum, F. sambucinum var. coeruleum and F. solani), suggest that the effects on swine may be due to trichothecenes produced by fusaria within fruits, and that eating damaged chayotes is dangerous for animals. PMID- 2103641 TI - [Socioeconomic aspects of subjects with imported malaria in the metropolitan area of Sao Paulo, Brazil. I. Characterization of the population and knowledge about the disease]. AB - With a view to discovering the social and economic characteristics of people from endemic malarial areas of Brazil, 566 suspected malaria cases were studied at the S. Paulo City Metropolitan Region Malaria Laboratory. Data were obtained by means of the application of standardized questionnaires over the period from November 1986 to June 1987 to individuals with as history of transit to Brazil's endemic malarial region. Of the population studied, 345 (61.0%) lived in the endemic area; 479 (84.6%) were males, 513 (90.7%) were between 15 and 55 years old and 307 (54.2%) presented positive plasmodium haemoscopia. The analysis by educational level indicated that 486 (85.9%) had primary or secondary education; 109 (19.3%) worked in mineral extraction; 74 (13.2%) were farmers, and 46 (8.1%) were related to terrestrial transportation activities. With respect, to knowledge of the disease, 384 (67.8%) had at least 1 bout of malaria before and 491 (86.8%) associated the disease with the presence of the vector. Of the 221 residents in S. Paulo, 207 (93.7%), as well as 336 (97.4%) of those residing in the endemic area already know of the risks of infection prior to travelling through the area of transmission. The interval between the first symptoms and the seeking for medical care varied from 0 to 3 days in 386 cases (68.2%). The frequencies of the variables studied analysed according to the haemoscopic result and the place of residence, were statistically significant. PMID- 2103642 TI - [Evaluation of the sensitivity of adult Culex quinquefasciatus Say to chemical insecticides]. AB - The sensitivity of the adult house mosquito Culex quinquefasciatus to 5 chemical insecticides was evaluated under laboratory conditions, based on the Median Lethal Time (LT50) criterion. The organophosphorous Malathion and four pyrethroids: Bifenthrin, Deltamethrin, Esfenvalerate and Alfamethrin were utilized. An easy and efficient technique was suggested for the testing of one day-old adults, including five repetitions for each treatment. The results revealed the full adequacy of this method for routine use. Further, no resistance to the 5 chemical compounds was detected among this natural population of Cx. quinquefasciatus. PMID- 2103643 TI - Peroral susceptibility of Aedes albifasciatus and Culex pipiens complex mosquitoes (Diptera: Culicidae) from Argentina to western equine encephalitis virus. AB - The transmission cycle of western equine encephalitis (WEE) virus in South America is unknown. A WEE virus strain was isolated from Aedes albifasciatus in Argentina during the WEE epizootic of 1982-83. Also, Culex pipiens from Argentina was reported to be able to transmit WEE virus experimentally, but other results indicate that Cx. pipiens from the USA is refractory to this virus. We determined the susceptibility of Argentina strains of Ae. albifasciatus and Culex pipiens complex mosquitos to infection by WEE virus by the oral route. Adult females were fed on chicks infected with a WEE virus strain isolated in Cordoba Province, Argentina, or were fed on a blood/virus suspension. Each mosquito ingested between 10(1.6) to 10(6.4) vero cell plaque-forming units of virus. Each of 28 Ae. albifasciatus was positive for virus from the fourth day postfeeding, and there was evidence for virus replication. In contrast, 0/44 Cx. p. quinquefasciatus and only 1/15 Cx. p. pipiens was positive. Aedes albifasciatus is susceptible to infection by WEE virus and should be considered a potential vector of this virus in Argentina. Both subspecies of Cx. pipiens are refractory to peroral infection by WEE virus and probably do not play a role in the WEE virus cycle in Argentina. PMID- 2103644 TI - [Seroprevalence and risk factors for hepatitis B virus infection by AgHBs and anti-HBs markers in prisoners and prime blood donors]. AB - Two cross-sectional surveys on hepatitis B virus (HBV) infection were carried out among 1,033 volunteer first-time blood donors in five blood banks (3 private, 2 public) and among 201 prisoners in the Penitentiary Center of Industrial Activity, in Goiania, Central Brazil, between June 1988 and February 1989. Those surveys were part of a major study designed to estimate seroprevalence of HBsAg and anti-HBsAg markers by ELISA test, and to study risk factors associated with seropositivity. The presence of any serum marker was considered as previous exposure to HBV. A standard questionnaire was applied to both populations to evaluate previous blood transfusion, number of sexual partners, homo/bisexual activity, history of sexually transmitted diseases, drug abusers, use of parenteral medicine, acupuncture, tattooing and VDRL seropositivity. Seroprevalence varied from 12.8% to 26.4% in blood donors and prisoners, respectively, (p less than 0.05) and increased with age (X2 trend=14.0 p less than 0.05%). Prisoners had higher percentages of all risk factors investigated than blood donors, with the exception of number of sexual partners. Among all risk factors studied, age, imprisonment and tattooing were statistically associated with seropositivity, even after multivariate analysis controlling for age and reclusion. The paper discusses the methodologic issues related to this epidemiologic investigation. PMID- 2103645 TI - [Risk factors for chronic non-communicable diseases: a domiciliary survey in the municipality of Sao Paulo, SP (Brazil). Methodology and preliminary results]. AB - The non-communicable chronic diseases are important causes of death in Brazil, mainly in the great urban centres. There are various risk factors related to these diseases, whose remotion or attenuation would contribute to a fall in mortality. The methodology of the first comprehensive multicenter study into risk factors of non-communicable chronic diseases carried out in Latin America is explained. In Brazil, this study was carried out in the cities of S. Paulo, SP and Porto Alegre, RS. Preliminary results from the city of S. Paulo as to the prevalence of arterial hypertension (22.3%), tabagism (37.9%), obesity (18.0%), alcoholism (7.7%) and sedentarism (69.3%) are presented. These results are compared with existing data from Brazil and other countries, and the relationship between various risk factors and the mortality from cardiovascular diseases in S. Paulo and some developed countries is discussed. PMID- 2103646 TI - [Epidemiological surveillance system for occupational accidents: experience in the northern area of the municipality of Sao Paulo (Brazil)]. AB - The epidemiological approach to occupational accidents and diseases adopted in Brazil is inadequate for many reasons, among them being: 1) the fact that only employers may notify work accidents, thus permitting notorious undernotification of these occupational hazards; 2) the available information does not permit a better understanding of the causal relationship between work accidents and diseases; 3) the official policy exists only for purposes of insurance compensation. The official documents for occupational disease and accident registration are the CTA (Work accident report) and FTA (Casualty treatment card). The Worker's Health Program of SUDS-R-6 proposed, in October, 1988 a method for the codification, registration in a micro-computer data bank and analysis of this information, based on the records presently in use (CAT) for public health service planning and accident prevention purposes. The major interest was in identifying the most common types of accidents in the region and the work environments in which they most frequently occur. The target population were the workers who attended the health units lisenced to deal with work accidents and diseases, in the Northern region of S. Paulo City. The data presented below refer to the months of October, November and December, 1988, the first three months of the project. During that period a total of 2,339 accidents were registered. They were classified as: typical work accidents - 87%: commuting accidents which occurred between the home and the work-place--18% and work diseases (only 2 cases). The majority of workers (50%) were between 25 and 45 years of age, approximately 7% were under 18. Male workers represented 83.2% of accident cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103647 TI - [Prevalence of dental caries in a school population of the Amazonian region]. AB - In view of the lack of data as to the prevalence of dental caries among typical amazonian populations, the authors carried out an epidemiological study of 103 schoolchildren from Sirituba Island, Abaetetuba, Para, Brazil. The mean values found for DMFT and deft were 6.5 and 5.4 respectively. Although the region is very primitive, this high prevalence may be linked to several factors, among which is the urban influence, mainly through the use of sugar, on food habits in such a way as fundamentally to alter the diet of the amazonian population. PMID- 2103648 TI - [Risk factors associated with infant mortality in 2 areas of the metropolitan region of Sao Paulo (Brazil), 1984-1985. Proposal for predictive instruments]. AB - The application of the concept of "risk" to maternal and child health was studied, the starting point being the World Health Organization's proposal for a "risk approach" in health services. The study was concerned with the development of a scoring system for the identification of groups at high risk of death during the first year of life, whether in the neonatal or the post-neonatal periods, and was based on a case-control study. The case group consists of children under one year of life, whose deaths had been registered during the years of 1984 and 1985 and whose parents lived in Cotia and Vargem Grande Paulista (149 cases). The control group was a probabilistic sample of 216 children born in 1984, which survived the first year of life and whose parents lived in the same area. All the mothers were interviewed by means of a questionnaire for the identification of independent variables associated with infant death. The statistically associated variables were grouped in four scales: to be used, respectively, in the antenatal period, prior to delivery and in the neonatal and post-neonatal periods. The variables were weighted in the scales according to the values of the odds ratio, and they have different cut points, each one having its own sensibility, specificity and predictive value. PMID- 2103649 TI - [The quality of the filling-in of death certificates of children below one year of age in the metropolitan area of Rio de Janeiro]. AB - Within the scope of an investigation into infant mortality determinants in the metropolitan region of Rio de Janeiro during one-year period, the original death certificates of a sample of children were studied and compared with information provided on them by hospital case-histories and records. This was done with a view to assessing the quality of the filling in of certificates for the purpose of calling the attention of health officers to their use as documents furnishing data for the preparation and evaluation of health programmes and note simply as a legal requirement for burying. Only 52.3% of the basic causes given on the certificates were maintained after the examination of the case histories. Necropsy was carried out on only 42.8% of those neonatal deaths and 21.5% of post neonatal deaths which took place outside the hospital. Other items that were evaluated included mother's age and education, time interval and complementary examination, birth weight and necropsy, all of which presented a degree of accuracy in their filling-in far below that required, thus evidencing the limitations of the official death statistics based on this information. PMID- 2103650 TI - [Findings of Phlebotominae (Diptera: Psychodidae) in the southern coast of the State of Sao Paulo, Brazil]. AB - Five species of phlebotomine sandflies were caught on the Southern part of the coast of S. Paulo, Brazil. CDC-light and Shannon traps were used, as well as human-bait, during two investigations into Culicidae mosquitoes. Lutzomyia intermedia and L. flaviscutellata were found among those sandflies. The localities investigated were swampy environments and scant human cases of cutaneous leishmaniasis have been notified there. Both situations suggest the autochthonous nature of the human cases registered there. PMID- 2103651 TI - [Malaria outbreak in users of injectable drugs]. AB - An outbreak of Plasmodium vivax malaria among drug addicts in Bauru, S. Paulo State, Brazil, is reported. Until July 1989, 12 cases had been confirmed by thick smear examinations and 20 contacts were being investigated. All of them reported frequent use of intravenous cocaine and sharing of needles and syringes but deny having travelled through endemic malarial areas. PMID- 2103652 TI - [Measles in rural workers: a methodological essay in social epidemiology]. AB - The study of a measles epidemic in the Ribeirao Preto region, in 1984, showed a high proportion of cases occurring among people above 15 years of age. This finding led to the identification of a particular characteristic of the disease's distribution in the area, i.e. the high incidence among rural workers (especially those restricted to collective lodgings when working in agricultural and industrial activities related to sugar cane plantations). A methodological exercise of synthesis between the descriptive phase of the traditional epidemiology and the was carried out. This procedure aimed at incorporating some aspects of the social process of the area with a view to explaining this particular distribution of measles as a result to that social process (i.e. the pattern of the occurrence of measles among rural workers is understood as a historically determined social event). Finally, the need to consider the appearance of specific diseases in different human groups according to the social process into which they are inserted in disenssed in such a way that their history and specificity are taken into account. PMID- 2103653 TI - [Treatment of hypertension and the decline of mortality caused by cerebrovascular accidents]. AB - A possible cause-effect relationship between the decline of mortality from cerebrovascular accidents (CVA) and a better control of arterial hypertension is discussed. The international literature on the subject is critically reviewed in the light of the possible statistical artifacts for enumeration of CVAs, the incidence and fatality of the disease, the prevalence of other risk factors such as hypercholesterolemia, smoking, and the consumption of sodium, potassium and alcohol, and obesity, as well as the contribution of health care. PMID- 2103654 TI - Experimental study of renal sympathetic nerve activity during left ventricular assist device pumping. AB - To determine the effect of left ventricular assist device (LVAD) pumping on sympathetic tone, renal sympathetic nerve activity (RSNA) was recorded in acute animal experiments. Our TH-7B pneumatically driven sac type ventricular assist device (VAD) was used in 7 adult mongrel dogs. RSNA was detected by use of bipolar electrodes attached to the left renal sympathetic nerve under conditions of various LVAD pumping modes. All hemodynamic data and the RSNA were calculated with a personal computer system. In general, LVAD assistance produced increased systolic aortic pressure, increased pulmonary artery flow and decreased left atrial pressure, which caused decreased RSNA, especially in the counterpulsation mode. These results suggest that renal vascular resistance might be reduced in parallel with the decrease of RSNA. Thus, counterpulsation mode LVAD assistance has the more evident effect in preventing acute prerenal renal failure. PMID- 2103655 TI - Characteristics of cerebral glucose utilization in dementia. AB - To make clear the characteristics of cerebral glucose uterization in dementia, PET studies with 18F-FDG were carried out. Taking the pattern of 18F-FDG uterization, dementia can be subdivided into two types. One type shows a simultaneous and symmetrical reduction glucose uterization in the posterior part of neocortex covering the temporal, parietal and occipital association cortices. This is referred to as type I. Although this type constitutes only about 1/5 of all dementia patients, it is considered the fundamental type of dementia. Aside from this, there is type wherein a simultaneous and symmetrical reduction in glucose uterization of the neocortex. This is type II. It constitutes about 4/5 of all dementia patients which is far more type I. There are no essential difference in the characteristics of cerebral glucose uterization in AD and MID. However, with regards the mean, AD is lower than MID. Various organic defect in neocortex do not correlate with the global reduction in glucose uterization in dementia patients. These results suggest that the reduction in glucose uterization in dementia may be functional disorder. PMID- 2103657 TI - Multidrug resistance. PMID- 2103656 TI - Severe atrophy of amygdala and hippocampus in both Alzheimer's disease and multi infarct dementia. AB - Alzheimer's disease and multi-infarct dementia are the two main diseases entirely different from each other producing almost the same abnormalities as dementia syndrome. With magnetic resonance imaging, severe atrophy of amygdala and hippocampus in both Alzheimer's disease and multi-infarct dementia was observed. There was no essential difference on the atrophic findings between Alzheimer's disease and multi-infarct dementia. This result therefore suggest that the quantitative measurement of amygdaloid and hippocampal atrophy predicts dementia. PMID- 2103658 TI - Limbic system, the main focus of dementia syndrome--a study with MRI and PET. AB - Alzheimer disease and multi-infarct dementia are two entirely different diseases producing almost the same abnormalities as dementia syndrome. The statistical studies with MRI to locate the focus of dementia syndrome in the neocortex was an absolute failure. With MRI there is drastic atrophy and destruction of the amygdala and hippocampus suggesting the limbic system as the focus of dementia syndrome. Destruction of the limbic system in particular amygdala and hippampus produced the functional obstruction brought about by the marked reduction in the glucose utilization with PET in the bilateral temporal, parietal and occipital association cortices. Although this type constitutes only about 1/5 of all dementia patients. It is considered the fundamental type of dementia syndrome. Aside from this, there is a type wherein simultaneous and symmetrical reductions in glucose uterization of the frontal association cortex and the motor association cortex in the anterior part of the neocortex. This is referred to as type II. It constitutes about 4/5 of all dementia patients which is far more than type I. Based on these results, it is thought that limbic system is the main forcus of dementia syndrome. PMID- 2103659 TI - Uptake by foods of tetrachloroethylene, trichloroethylene, toluene, and benzene from air. AB - Transition rates from air into food as well as equilibrium concentrations in air and critical foods were determined for tetrachloroethylene, trichloroethylene, benzene and toluene. From these data, maximum concentrations of the four substances in air were estimated that keep contamination of critical foods at an acceptable level. A simple and rapid method allowed us to determine the risk of food contamination from the air, e.g. in shops and kitchens, by the analysis of the air. Estimations showed that concentrations in the air of shops should not exceed 1 mg/m3 if tetrachloroethylene concentrations in foods are limited to 100 micrograms/kg (slightly higher concentrations can be accepted for the other three compounds); in kitchens of restaurants and households, even 0.3 mg/m3 cause the target concentration to be exceeded rather frequently If the limit in foods is 50 micrograms/kg, recommended maximum concentrations in air are 0.5 and 0.15 mg/m3. The data also shows that the recommended limits for concentrations in air conflict with the accepted emission limits: If emission at the accepted limit occurs near shops or households, contamination of foods far exceed that considered as tolerable. PMID- 2103660 TI - [The analysis of polycyclics in vegetable samples]. AB - PAH analyses in vegetables are often difficult to carry out; therefore two different clean-up methods, which allow elimination of interfering matrix components such as essential oils, waxes, carotinoids and chlorophylls were developed. Clean-up of 32 different vegetables samples consisted of either Bio Beads S-X3 chromatography or semi-preparative HPLC on silica gel Si-60. PAH were determined by capillary GC-MS, which allowed the application of deuterium-labeled internal standards. The results are presented; higher PAH contamination was detected in kale and parsley. PMID- 2103661 TI - [Cesium 134 and 137 contamination of game killed in Hesse]. AB - The amount of caesium 134 and 137 in Hessian game hunted for food (556 animals) after the reactor accident at Chernobyl was investigated. Comparisons have been made before and after the accident. Although there was only a very low level of contamination, the contamination rate of different species varied; on average, the Red Deer showed the highest activity (130 Bq/kg). The level of caesium contamination was mostly influenced by the permanent habitat of the animals. The main influence was due to regional, geographical and meteorological conditions. The influence of age or sex could not be determined. The contamination rate was shown to decrease with time. PMID- 2103663 TI - [Retropharyngeal-esophageal tumors: clinical and therapeutic aspects]. PMID- 2103662 TI - [Myoglobin content and beta-hydroxyacyl-CoA-dehydrogenase activity of different muscles of cattle and calf]. AB - The heart, tongue, jowl, diaphragm and tail as well as shoulder, top round, the longissimus dorsi muscle of slaughtered cattle and the diaphragms of calf were examined with respect to their myoglobin content and beta-hydroxyacyl-CoA dehydrogenase (HADH) activity. According to Gottesmann and Hamm [1] the product of these two values, the so-called MH value, can serve as the differentiation between the diaphragm and "normal cross striated skeletal muscles". Like the diaphragm, heart, tongue and jowl of cattle show higher MH values than those of "normal beef". Muscles in the tail have the same MH values as those of normal beef muscles. There are no essential differences in the MH values of various cross-striated muscle types of cows and calves. Muscles of cattle show a slightly higher myoglobin content, whereas the HADH activity is lower than in veal. PMID- 2103664 TI - [Thymoma: results of 241 operated cases]. PMID- 2103665 TI - [Neoplastic pathology of the cervico-mediastinal junction. Diagnosis and treatment. Pathological anatomy and epidemiological data]. PMID- 2103666 TI - [Tumors of connective origin]. PMID- 2103667 TI - [Pancoast's tumor]. PMID- 2103668 TI - [Principles of radiotherapy in tumors of the cervico-mediastinal junction]. PMID- 2103669 TI - [Cervico-mediastinal complications in cervical surgery and radiotherapy (tracheal excepted)]. PMID- 2103670 TI - [Tracheal sequelae secondary to cervico-mediastinal diseases and their treatment]. PMID- 2103671 TI - [Physiopathology and syndrome of the superior mediastinum]. PMID- 2103672 TI - [Diagnostic images of the cervico-mediastinal junction]. PMID- 2103673 TI - [Neoplastic pathology of cervico-mediastinal junction. Diagnosis and treatment. Endoscopic instrumental diagnosis]. PMID- 2103674 TI - [Neoplastic pathology of the cervico-mediastinal junction. Diagnosis and treatment. Routes of approach]. PMID- 2103675 TI - [Impossibility of radical lymph node dissection in the superior mediastinum using cervical approach]. PMID- 2103676 TI - [Technique of lymph node dissection]. PMID- 2103677 TI - [Diagnostic problems concerning cervico-mediastinal lymph nodes]. PMID- 2103678 TI - [Carcinoma of the thyroid gland with cervico-mediastinal extension]. PMID- 2103679 TI - [The cervico-mediastinal region]. PMID- 2103680 TI - [Tumors in ectopic parathyroid glands]. PMID- 2103681 TI - [Peristomal recurrences]. PMID- 2103682 TI - Cerebral function in hepatic encephalopathy. PMID- 2103683 TI - Synaptic plasma membrane composition and fluidity in the pathogenesis of hepatic encephalopathy. PMID- 2103684 TI - Metabolic effects of carnitine and carnitine analogs. PMID- 2103685 TI - Clinical use of carnitine. Past, present and future. PMID- 2103686 TI - New roles of carnitine metabolism in ammonia cytotoxicity. AB - High levels of ammonia in blood and brain due to metabolic disorders are associated with neurological abnormalities. Although the mechanism of ammonia toxicity at the CNS level is still unknown, alterations in brain energy metabolism, in neurotransmitter function and direct effects on nervous impulse have been proposed. In most hyperammonemic conditions morphological changes in the liver and brain have been demonstrated, especially in mitochondria, endoplasmic reticulum and lysosomes, together with an accumulation of intracellular lipids. The treatment of hyperammonemias is uncertain and mostly directed to reduce the level of circulating ammonia; there is no current therapy aimed to counteract the molecular effects of ammonia. Administration of carnitine prevents acute ammonia toxicity and enhances the efficacy of ammonia elimination as urea and glutamine. In addition the cytotoxic effects of ammonia, possibly arising from lipid peroxidation, are ameliorated by carnitine. These data indicate the feasibility of utilization of carnitine in the therapy of human hyperammonemic syndromes, both for reducing the levels of ammonia and preventing its toxic effects. PMID- 2103687 TI - Effect of L-carnitine upon ammonia tolerance test in cirrhotic patients. AB - In a group of liver cirrhosis (LC) patients subjected to a rectal ammonium overload test, the effect of L-carnitine on ammoniemia and on the type A numerical connection and star clock psychomotor tests has been evaluated. On comparing 40 LC patients given L-carnitine with 40 control cirrhotics given a placebo, no significant differences were observed in ammonium levels after performing the overload test in both groups. However, on studying the patients with the greatest liver involvement, those given L-carnitine showed smaller elevations in ammoniemia and better responses to the psychometric tests than those receiving the placebo. The results obtained emphasize the need to continue testing the effect of L-carnitine using either similar tests or carrying out long term evaluations to determine its protective effect in the appearance of hepatic encephalopathy, perhaps even including its evaluation in the treatment of established encephalopathy. PMID- 2103688 TI - Metabolism of sedatives in liver disease. PMID- 2103689 TI - Branched chain amino acids in the treatment of hepatic encephalopathy. PMID- 2103691 TI - Treatment of portal systemic encephalopathy: the old and new treatments. PMID- 2103690 TI - Ammonia metabolism in normal and portacaval-shunted rats. AB - Ammonia is generated from a large number of metabolically important reactions. Despite its central importance in whole body nitrogen homeostasis excess ammonia is neurotoxic and its concentration must be kept low. Ammonia generated in most extrahepatic tissues is detoxified by incorporation into glutamine (amide). This glutamine may be used in a number of biosynthetic reactions (e.g. in pyrimidine synthesis). Alternatively, as a means of maintaining nitrogen balance, glutamine may be released to the blood. Resting skeletal muscle is particularly important 1) as a "sink" for removal of blood ammonia, and 2) as a major source of circulating glutamine. However, during vigorous exercise skeletal muscle may become a net contributor of ammonia to the blood. A few tissues and cell types (e.g. lymphocytes, macrophages, enterocytes, colonocytes, thymocytes, fibroblasts, bone) and tumors exhibit marked rates of glutamine utilization. In the kidney, glutamine is an important source of urinary ammonia. Ammonia generated from 1) the breakdown of nitrogenous substances in the gut, and 2) from the use of glutamine as a metabolic fuel in the small intestine, is taken up by the liver wherein it is detoxified by conversion to urea and to a lesser extent, glutamine. Some portal vein glutamine acts as a source of urea nitrogen. Ultimately, however, most excess ammonia nitrogen is detoxified indirectly (via glutamine (blood)----glutamine (small intestine)----ammonia (portal vein) or directly in the liver as urea. Portal-systemic shunting of blood, as occurs in chronic cirrhosis of the liver or following the surgical construction of a portacaval shunt results in portal blood bypassing the normal ammonia detoxification machinery of the liver. Under this condition blood ammonia levels rise markedly, increasing the burden on extrahepatic tissues, such as skeletal muscle, brain, and kidney, in maintaining ammonia homeostasis. The most commonly employed animal model of human liver disease is the rat in which an end-to-side portacaval shunt (PCS) has been surgically constructed. Brain glutamine synthetase activity is not increased in PCS rats and in some areas of the brain there may even be a decrease in activity. The brain glutamine synthetase appears to be working at near maximal capacity. Thus, the PCS rats exhibit profound neurological dysfunction when administered ammonium salts in amounts easily tolerated by normal animals. Because of the limited capacity of brain to remove excess ammonia, a rational approach to the treatment of patients with liver disease should include a regimen directed toward lowering the associated hyperammonemia. PMID- 2103692 TI - Benzodiazepine antagonist in the treatment of human hepatic encephalopathy. AB - Recently it was suggested that hepatic encephalopathy (HE) is mediated by an increased GABA-ergic tone. The logical consequence of such a hypothesis is the use of antagonists of the GABA -benzodiazepine receptor for treatment of HE. The experience with these drugs in human HE is limited. In order to get an estimate of the efficacy of this type of drug in humans 20 consecutive episodes of HE in 17 patients with acute or chronic liver failure were treated with flumazenil. All patients entered into the study were encephalopathic for up to 120 hours and failed to respond to conventional therapy. After an observation period of 8 hours, 15 mg of flumazenil were infused intravenously over 3 hours. Before and after treatment patients were examined neurologically and the Glasgow coma scale was calculated. In addition, somatosensory evoked potentials were recorded. In 5 out of 11 episodes in 10 patients with fulminant hepatic failure and in 7 out of 9 episodes in 7 patients with cirrhosis an unequivocal amelioration of HE was observed. The response to treatment occurred very rapidly. After stopping treatment in 8 out of these 12 episodes HE worsened again after 2 to 4 hours. The favourable clinical response was also documented by improvement of somatosensory evoked potentials. In 5 of the 8 episodes not reacting to flumazenil patients had signs of increased intracranial pressure. These findings indicate that flumazenil may be valuable in treatment of acute HE occurring in fulminant hepatic failure or in decompensated cirrhosis. PMID- 2103693 TI - Nitrogen metabolism in normal and cirrhotic liver. PMID- 2103694 TI - Hyperammonemia induces brain tubulin. AB - We have developed an animal model of hyperammonemia consisting of feeding rats a diet containing ammonium acetate. Using this model we have found that hyperammonemia induces tubulin synthesis in brain. Initially tubulin accumulates rapidly (28% after 2 days on diet) and continues increasing but at a slower rate, reaching a 50% increase after 100 days on the diet. The effect is reversible, rats fed the ammonium diet return to normal levels of tubulin two days after withdrawal of the ammonium diet. In contrast to the effect on brain, hyperammonemia did not increase tubulin content in liver or kidney. Moreover, the effect on brain is selective, with maximum increases of tubulin content in hippocampus, septum and reticular formation while other areas such as locus coeruleus and mammillary nucleus are not affected at all. The results presented show that the induction of tubulin is a consequence of an increased polymerization of microtubules which in turn is due to an altered phosphorylation of microtubule-associated proteins. PMID- 2103695 TI - Astrocytes in hepatic encephalopathy. PMID- 2103696 TI - Effects of NH4+ on the function of the CNS. PMID- 2103697 TI - [Effect of position with respect to gravitational force on the hydrodynamics of an experimental model of saccular aneurysm]. AB - We wish to confirm the hypothesis that the hydrodynamics of brain aneurysms depend partially on their position, with respect to the force of gravitation, and so developed an experimental model of latex aneurysms, which was subjected to a pulsatile flow. Four different registers were made with an injection of ink and radioisotopes. A physical model was designed which allowed a quantitative analysis of the results and which allows a mathematical analysis of the aneurysm's hydrodynamics. The results suggest that when an aneurysm is oriented against the force of gravity, it has a very low risk of thrombosis, and the scarce turbulence of the flow condition a lower risk of growth and rupture, in comparison with other conditions. The greatest flow turbulence against the wall is found in the aneurysm oriented downwards, that is parallel to the force of gravity. Due to its hydrodynamics, the downwards aneurysm has the highest probability of complication, since it has; a) higher risk of rupture due to the impact of the stream upon the wall and to the turbulence this impact produces, b) a higher risk of thrombosis produced by the circulatory stasis which has a dome. This combination of factors (rupture and thrombosis) allows these aneurysms to grow more than others. PMID- 2103698 TI - Neurotoxicity of thallium: biochemical and morphological study of organic lesions. AB - A biochemical study of experimental thallium intoxication in newborn rats and its morphological consequences upon the brain of developing animals was undertaken. The thallium content was analyzed in the following encephalic regions: hippocampus, hypothalamus, mesencephalon, cerebellum, and cortex. One day after application of the toxic substance, a homogeneous distribution of the metal in the brain was found. Thallium concentrations in the mentioned regions were twice as high as those found in an adult rat, at the same dosage, 20 newborn Wistar rats were used for the histopathological study. 5 remained as witnesses, the rest received a single injection of thallium of .07 ml. of a solution with a concentration of .32 mg/Kg. 3 rats were sacrificed at 24, 48 and 72 hours; 3 at 7 days and 3 at 51 days. The brain , sciatic and crural nerves were fixated in 10% formaldehyde for 15 days. Cuts in paraffin and frozen sections measuring between 5 and 7 microns were taken from the fragments of different areas. These were stained with aniline methods (Masson, Gallego and H-E) and silver-gold impregnation as modified by Rio-Hortega. PMID- 2103699 TI - [C-peptide measurement in patients with type II diabetes mellitus: its possible use in the insulin therapy decision]. AB - Considering pancreatic reserve recognition a more rational basis for starting insulin therapy in NIDDM, during 1988 we studied fasting and post-breakfast plasma C-peptide levels in 31 patients (21 w, 10 m, mean age 48.2 +/- 17.7 yr), referred to our department for insulin therapy evaluation because of primary or secondary failure to other measures. Major features were obesity and chronically uncontrolled illness. Our patients were categorized as follows: group A, considered non responders which included four patients; group B, taken as responders consisting in seven; and a remaining of 20 hyperresponsive patients which formed group C; these with patients of group B, embodied an 87.1% of patients. Among nonresponders there was no any case of total B cell loss of function, and plasma C-peptide activity surpassed through those limits considered for ketoacidosis. We believe that these patients should be eligible candidates for insulin therapy. We failed to found out correlation of plasma C-peptide activity with either age or duration of illness. Our observation supports that fasting plasma C-peptide evaluation would suffice for pancreatic reserve evaluation. We conclude that our patients mainly presented an insulin resistant state associated with obesity thus enhancing the commonplace call for reinforcing nonpharmacologic treatment modalities such as caloric restriction, weight loss and exertion to achieve a better control in NIDDM patients. PMID- 2103700 TI - [Identification of inborn errors of galactose metabolism in patients with cataracts]. AB - 133 patients with congenital or idiopathic cataracts were studied (94 patients had ages between 1 month and 14 years; 10 patients had ages between 16 and 50 years and 29 patients did not have an age registry) along with 18 patients with a clinical diagnosis of classic galactosemia. The activity of galactokinase (GALAK) and that of erythrocyte galactose-1-phosphate uridyl transferase (GALT) was measured. There were no individuals with a total deficiency of GALK or GALT. The cataract patients of ages between 1 monthly and 14 years, 3 (3.19%) and 4 (4.25%) showed GALK and GALT levels in the range corresponding to the respective heterozygotes. As compared with the expected incidence of heterozygotes in the general population (0.2% for GALK and 0.8% for GALT) we found a significant rise of individuals with low levels of enzymes for the metabolism of galactose. The possibility that heterozygote galactosemic states contribute a risk factor in the development of cataracts and its therapeutic implications are discussed. PMID- 2103701 TI - [Granulocyte-macrophage colony-stimulating factor in the treatment of secondary bone marrow suppression in patients with lymphoma. Preliminary report]. AB - Four patients with severe myelosuppression secondary to chemotherapy for advanced malignant lymphoma were treated with human granulocyte macrophage colony stimulating factor (GM-CSF) at dose of 10 micrograms/kg/day. The number of absolute granulocytes increase in all patients in the first 3 days after the treatment was begun. Normal values were observed after 5 days on treatment. No toxicities resulted from the treatment. The results demonstrate the utility of GC CSF in restoring normal granulocytes counts in patients undergoing intensive chemotherapy. PMID- 2103702 TI - [Mast cells in Peyer's patches in the mouse]. AB - Mast Cells participate in immediate and late hypersensitivity activities, immunoregulation and inflammation. Recently two groups of them have been detected on the basis to its morphology, content of granules and function: a) Those who are localized in connective tissue and b) Those of the intestinal mucosa. Those of the intestinal mucosa are T dependent and proliferate in parasitic as well as in intestinal hypersensitivity conditions to diverse antigens, in turn, Peyer's Patches (PP) are considered antigen catcher and initiators of intestinal immune responses; these are subject to the influence of diverse substances, several of which are within mast cells (for example: histamine, prostaglandins, etc); for which in this work we investigate the morphology relation between PP and mast cells. Balb/c mice small intestine segments with muscular layer and PP of proximal, middle and distal levels where studied; were histologically processed, toluidine blues stained and mast cells counted in different intestinal layers (PP underlying zone, rest of the muscular, corium and submucosa. Data were analyzed by the paired double T test for mean differences. A greater Quantity of mast cells were observed at the marginal zone of the PP in comparison to the rest of the muscular layer, submucosa and corium. The abundance of mast cells in relation to the PP possibly indicates its modulatory influence on the function of lymphoid cells of the PP. PMID- 2103703 TI - [Flow characteristics in 3 kinds of heart valve prosthesis]. AB - Transvalvular turbulence caused by the blood flow in implanted cardiac valvular prosthesis is the cause of thrombosis at the post-valvular region. The literature in this connection indicates that thromboembolic complications are more common with the tilting disc mechanical valves. In order to study the turbulence caused by porcine biological prosthetic valves, by a caged-ball Biomed mechanical valve and by a tilting disc Bjork-Shiley valve, a device was developed which permits to visualize and to photograph flow characteristics in the three types of valves with the purpose of determining the degree of turbulence generated in each case. An additional accessory equipment was devised for the purpose of measuring static and dynamic pressures at various levels of the test tube containing the prosthetic valve wherein the variations in pressure reflect the degree of turbulence. The data obtained from 500 pressure registrations were analyzed in a computer. The data indicate that the porcine biological valve causes the least turbulence, whereas the mechanical valves create greater turbulence. Of the mechanical valves, the tilting disc prosthetic valve causes considerably greater turbulence, in particular in the vicinity of the smaller orifice. PMID- 2103704 TI - [Model of intraluminal perfusion of the guinea pig ileum in vitro in the study of the antidiarrheal properties of the guava (Psidium guajava)]. AB - An experimental in vitro model was developed for the study of plant extracts reported by traditional medicines in the treatment of diarrhea. The guinea-pig isolated ileum is perfused with the plant extract using an intraluminal approach. The peristaltic reflex is induced by electrical stimulation while the plant extract is perfused. The spasmolytic effects of Psidium guajava leaf methanol, hexane and water extracts were demonstrated suggesting the existence of two different types of active components. The results obtained allow to propose this in vitro method as a useful model to reproduce some of the characteristics of the oral way of administration of plant extracts. PMID- 2103705 TI - [Pharmacological properties in vitro of various extracts of Mimosa tenuiflora (tepescohuite)]. AB - The in vitro biological effects of polar extracts of Mimosa tenuiflora (Willd.) Poir. trunk bark (tepescohuite) were studied. Ethyl acetate extract, with a high tannin content, inhibited the growth of different microorganisms. Alkaloids were particularly abundant in the butanol extract and this product strongly inhibited the intestinal peristalsis and produced contraction of uterine and gastric strips of rat and guinea pig. Saponins were detected in butanol and methanol extracts producing hemolysis. The screenings performed showed the diversity of bioactive compounds present in this plant product. PMID- 2103706 TI - [Effect produced by the alkaloid fraction of Mimosa tenuiflora (tepescohuite) on the peristaltic reflex of the guinea pig ileum]. AB - An alkaloidal fraction was obtained from Mimosa tenuiflora (Willd.) Poir (tepescohuite) trunk bark. The product contained mainly an indolealkylamine and three minor alkaloids. This fraction inhibited the peristaltic reflex in the guinea-pig isolated ileum in vitro. PMID- 2103707 TI - N,N-dimethyltryptamine alkaloid in Mimosa tenuiflora bark (tepescohuite). PMID- 2103708 TI - [Management using nimodipine of cerebral vasospasm secondary to subarachnoid hemorrhage caused by rupture of an intracranial aneurysm]. AB - The cerebral vasospasm secondary to subarachnoid hemorrhage due to the rupture of an intracranial aneurysm has a high morbidity/mortality. Its cause is still unknown, so we obtain controversial results after prevention and treatment. We studied two groups, of 29 patients each one, where the first was treated with systemic nimodipine, and the second was the control group. We did not observed any correlation between the clinic vasospasm or the symptomatic, and the radiographic one. There was no difference between the final results of both groups. No collateral effects were shown in other organs with the use of this agent. PMID- 2103709 TI - Bone mineral content, 25-hydroxycalciferol and zinc serum levels in insulin dependent (type I) diabetic patients. AB - To determine the relationship between bone mineral content (BMC), 25 Hydroxycalciferol (25OHD) and zinc serum levels in young insulin-dependent diabetics, we performed photon absorptiometry on a poorly controlled group of 22 patients. Zinc, 25OHD and alkaline phosphatase were measured in fasting serum. Ca, P, Mg, glucose and cAMP were determined in serum and in 24 hours urine collection. The diabetic group showed a significant decrease in BMC (less than 0.001) with raised urinary excretion rate of calcium (p less than 0.001). On the other hand, serum levels of zinc and 25OHD showed a significant decrease (p less than 0.001, both). We found a positive and significant correlation between glycosuria and urinary excretion rate of calcium (r = 0.77; p less than 0.001) and negative one for 25OHD and urinary excretion rate of calcium (r = -0.77; p less than 0.001). We conclude that decreased zinc and 25OHD serum levels in poorly controlled insulin-dependent (Type I) diabetic patients, in addition to raised urinary excretion rate of calcium, as result of the osmotic diuresis, contribute to bone loss in these patients. PMID- 2103710 TI - [Human fetal homograft to the nigrostriatal system for the treatment of Parkinson's disease]. AB - Four cases of transplant to the brain (striatum) of the ventral mesencephalic area (VMA) and three adrenal glands (A) to patients with Parkinson's disease are described as a new alternative for the improvement of this disease. The patients who received VMA showed a very significant improvement in the rigidity, bradykinesia, alterations in walking and posture, as well as the facial expression. Three of the four patients have returned to work. The group that received A tissue, showed a discreet improvement in the rigidity and bradykinesia, but none in the other signs of the disease. These patients are able to accomplish their daily needs, but two are unable to return to work. The differences which we observed between patients receiving VMA and A transplants, might be related to the heterogeneity of the disease, although we believe that the type of graft was responsible of these differences. Our results with the use of VMA, as well as that of other groups, are encouraging, although it is important to clearly establish that it is a procedure which is still in an experimental phase, requiring caution, and should only be practiced in highly qualified centers of clinical research. PMID- 2103711 TI - [Effect of in vitro infection with dengue virus (DEN-2) on various cellular immune response functions in the mouse]. AB - When Dengue type 2 virus (DEN-2) is put in contact with spleen cells from DBA/2 mice that had been stimulated with Concanavalin A, it was found a decrease in the incorporation of (3H) Thymidine. Furthermore it was observed that the number of Antibody forming cells (Plaque forming cells) against SRBC was decreased, when lymphocytes from DBA/2 mice spleen in culture, had been stimulated with sheep red blood cells (SRBC) in vitro and then infected with DEN-2 virus and the interleukin-1 (IL-1) biosynthesis was quantified in the thymocyte system it was shown that macrophages produced high levels of IL-1 compared with non-infected cells, and that this increased levels could be similar to that produced when macrophages are stimulated with lipopolysaccharide form E. Coli (LPS). The above mentioned results suggest that DEN-2 virus is able of altering some functions of the immune response concerning T and B lymphocytes. Furthermore, the infection of P388D1 cells induce in the first 24 hours an over production of IL-1 that could be the reason why in the natural infection in humans, patients run a fever in the beginning of the viremia caused by DEN-2 virus related with the property of IL-1 reported as endogenous pyrogen. PMID- 2103712 TI - Obstruction of the ventricular catheter of a CSF shunt system due to the own cyst of Taenia solium. AB - Five patients were studied who suffered secondary hydrocephalus due to neurocysticercosis. Shunt dysfunction was due to the obstruction of the ventricular catheter caused by the own cysticercus cysts. The Biomed system was used in four cases and the Hakim system in one. Valvular dysfunction was observed in patients within a period of 18 to 24 months after surgery, they had a history of several valvular dysfunctions. The diagnosis was made upon of extracting the catheter where the cyst was found to be attached to the ventricular brush. Subsequent evolution has not been satisfactory. The reasons for this complication are of a hydrodynamic and pharmacological nature and are also due to the growth of the cyst. This complication is not often suspected, therefore we recommend that in case of frequent valvular dysfunctions and asymmetrical hydrocephalus, studies like iodinetomography or magnetic resonance imaging be carried out in order to discard this possibility. PMID- 2103713 TI - [Activity of Opuntia streptacantha in healthy individuals with induced hyperglycemia]. AB - Hypoglycemia effect Opuntia streptacantha which occur in diabetic has not been found in healthy subjects. To find out if this effect appears also in healthy individuals if they are hyperglycemic, two tests were performed to 7 healthy volunteers. In both tests 500 ml of 20% dextrose were infused in two hours, 500 g of O. streptacantha were given orally before one test, and 400 ml of water as control were given before the other one. Serum glucose was measured every 30 minutes during three hours. Glucose rising was significantly (P less than 0.025) lower with Opuntia than in control test at 90 and 120 minutes (143 +/- 58 vs 193 +/- 9 and 135 +/- 25 vs 163 +/- 13 mg/dl respectively). Area under curve of glucose was also smaller in Opuntia than in control test (P less than 0.05). Hypoglycemic effect of O. streptacantha also occur in healthy subjects in hyperglycemia is present. PMID- 2103714 TI - From food basket to food security. The food factor in nutritional surveillance. AB - One important indicator of nutritional surveillance is the one devoted to monitor food security. The experience toward the development of one of such indicators is presented. This includes the development of a food basket, defined as the group of foods that meet the characteristics such as is now consumed by important population segments of the community; it contributes a substantial portion of the calories and proteins purchased, and is responsible for an important proportion of the food budget. The concept implies a dynamic food basket, the quantities of which are calculated in a way that simulates the behavior of the consumer and the best nutrition knowledge. For this purpose we use linear program techniques. A measure of the risk of being unable to buy the foods needed for a family is presented, and is used as a proxy for food security risk. In the appendix, the mathematical expressions of the model used for a linear program is also presented. PMID- 2103715 TI - [Variations in the individual consumption of table salt with or without chili in food, in a community of Mexico]. AB - The present study was carried out in a rural community in the central plateau of Mexico, with the objective of estimating the mean daily consumption of table salt at the family and individual level, and to determine if the individual taste to salt added to the food at the table, varied with the presence or absence of a hot species, "chile", to the food. Our results showed variability in three "barrios" of the community, which go from the central, more urban-type (Temascalcingo) to an intermediate-type (Boqui), and to a more rural-type (Bonsho), showing the highest mean consumption of salt at the family level in the most urban barrio (47.2 g/day), while the mean family consumption in the other two barrios (28.2 and 33.9 g/day, respectively) was lower. At the individual level, there were differences in salt consumption associated to sex and age. The highest consumptions were found in the more urban-type barrio, in which men in the 15-22 year-old group consumed a mean of 9 g/day, and women in the 7-14 year-old group consumed a mean of 6.37 g/day. When the individual taste for salt added to foods commonly prepared in the community were studied, we found a statisticaly significant difference in individual taste associated with the presence or absence of chile in the food. In two of the study meals (breakfast and lunch) the total grams of salt added to the food which did not contain chile was significantly higher than the salt added to the food which contained chile, suggesting that the presence of the specie may account for a great part of the need to enhance food flavor. This in turn could explain the smaller consumption of table salt in the more rural-type section of the population noted in the first part of the study, in which families tend to add more chile to their food than in the urban-type settings. PMID- 2103716 TI - Preparation of fish protein isolate and hydrolyzate (Mugil cephalus) and their incorporation into Mexican foods. AB - Fish protein isolates (FPI) and hydrolyzates (FPH) were obtained from mullet (Mugil cephalus) through alkali solubilization and HCl precipitation for FPI, as well as enzymatic hydrolysis for FPH. The powdered products showed solubilities of 50 and 89%, and emulsifying capacities of 36 and 39 ml oil/100 mg for FPI and FPH, respectively, with protein contents of 90% and oil contents lower than 1.6%. Both products were used to enrich cereals and legumes in order to increase their protein content and quality. The resulting mixtures were used to prepare common Mexican dishes. When up to 20 and 35% of the total protein was provided by FPI and FPH, respectively, the dishes were well accepted by 70% of the panel. PMID- 2103717 TI - [Chemical composition and nutritive value of the protein of Amaranthus quintensis]. AB - An account is given of some considerations concerning the chemical recognition and evaluation by biological methods of the quality of the flour obtained from Amaranthus quitensis seeds, submitted to grinding and sifting. The protein content of the flour (21.70g/100g) can be considered as very important, as well as that of the available lysine (5.20g/16gN). The calcium content was also remarkable (500mg/100g), and the starch ratio reached 45.00g/100g. The amount of nitrates found was 20.00mg/100g, which is an acceptable limit. The research for organic nitro compounds was negative. As for the biologic quality of the protein, the experiments revealed that it has quite an acceptable availability, as demonstrated by the following values: NPU = 42.50 +/- 6.10, D = 68.50 +/- 5.30, VB = 62, NPR = 2.10 +/- 1.80 and RNPR = 42. PMID- 2103719 TI - A brief history of the U.S. Department of Agriculture's Nutrient Data Bank. PMID- 2103718 TI - [Use of low-grade potatoes in the production of whole flour for the preparation of foods for popular consumption]. AB - A whole flour potato obtention process was developed which could be used in semirural areas. The potato without peeling was previously washed and ground adding 100 p.p.m. of sodium bisulphite, then it was dehydrated in a cabinet tray dryer with an air flow circulation set at 70 degrees C using three different deep beds (10, 20 and 25 mm). Finally it was milled, sieved and packed in polyethylene Kraft bags and stored for 10 months at room temperature. Results showed that drying time increased less rapidly when the bed depth was increased, so that the overall dryer productivity increased when increasing bed depth. Nevertheless, a better-quality product was obtained, as well as a greater process efficiency when a 10 mm bed depth was used. The whole flour had a particle size of 80 mesh and a moisture and protein content of 7 and 6.7%, respectively. No brown color formation or mold growth occurred during storage. "Tamales de dulce" and chocolate cookies were made with the flour obtained. These were subjected to an acceptability test at community level, and the test revealed that for both products, such acceptability was higher than 90%. PMID- 2103720 TI - [Effect of dietary concentration of Saccharomyces carlsbergensis yeast recovered from beer, in Warren male chicks]. AB - Six groups of 1-day-old Warren chicks (seven per group) were fed for 15 days on diets with the protein supplement made of mixtures of soybean protein and dried yeast Saccharomyces carlsbergensis recovered from beer. The purpose was to establish the maximum substitution level of the soybean protein isolate by dried yeast, with the least possible related metabolic effects. Each group was fed one of the diets containing 0%, 25%, 50%, 75% and 100% of the protein supplement based on yeast protein, substituting the soybean protein isolate. In order to estimate the NPR value of the yeast protein, a group which received a protein free diet, was also included. Protein utilization and changes in both plasma and liver total lipids, triglycerides, cholesterol and liver and kidney uric acid, were determined. In triglycerides, cholesterol and liver and kidney uric acid, were determined. In the groups fed diets with 75% and 100% of yeast protein, decreased body weight gain and PER and NPR values were observed, as well as an increment in the liver and kidney uric acid concentrations, although the diet consumption was not substantially modified. Thus, protein utilization, measured as PER and NPR, was lower in these groups. Plasma uric acid was not modified in neither group. The plasma lipids were not altered at whatever yeast concentration, while in the liver, total lipids as well as triglycerides decreased when the dietary yeast was increased. Results indicated that when using whole yeast cells recovered from beer in pre-starting rations for chicks, 50% of yeast protein is the maximum substitution level. PMID- 2103721 TI - Enteric-coated iron tablets. PMID- 2103722 TI - Use of cordocentesis in fetal hemolytic disease and autoimmune thrombocytopenia. PMID- 2103723 TI - The presence of Alzheimer's disease in a community population. PMID- 2103724 TI - Effectiveness of endoscopic drainage for pancreas divisum: endoscopic and surgical results in 31 patients. AB - Thirty-one patients with symptomatic pancreatitis and pancreas divisum were treated prospectively by inserting an endoprosthesis into the dorsal pancreatic duct for drainage. Pain was a feature characteristic of all 31 patients; of these 92% had an improvement in their subjective complaints of pain after sphincterotomy and insertion of a prosthesis in the minor papilla. During a two year follow-up period, 84% (26/31) of the group showed improvement in all the signs and symptoms associated with their pancreatitis, and this improvement was sustained in all patients for at least several months. A group of twenty-six patients subsequently underwent pancreatic surgery for recurrent symptoms. Those patients who had improved with endoscopic drainage did significantly better following surgical drainage than those who had shown little or no improvement with an endoprosthesis. On the basis of the above preliminary results, we recommend preoperative insertion of an endoprosthesis into the dorsal duct as a therapeutic predictor of eventual surgical outcome. PMID- 2103725 TI - A comparison of peripheral vasoconstrictor responses and cardiovascular autonomic function tests in diabetic patients. AB - Venous occlusion plethysmography has been used to measure sympathetic vasoconstrictor responses in the feet and hands to a deep breath and body cooling and to assess blood flow variability. Measurements were made in 14 non-diabetic control subjects and 52 diabetic patients, 30 of whom had evidence of peripheral neuropathy. All the measurements were significantly reduced in the feet of patients with neuropathy. Vasoconstrictor responses were not significantly impaired in the hands of these patients. Cardiovascular autonomic function was assessed in the same subjects by standard tests of reflex heart rate responses and compared to sympathetic vasoconstrictor function as determined by the response to a deep breath. Eighteen of the 30 diabetic patients with peripheral neuropathy had impairment of both cardiovascular and sympathetic vasoconstrictor function. Five had normal vasoconstrictor but impaired cardiovascular responses and two had normal cardiovascular but impaired vasoconstrictor function. It may therefore be important to assess both systems in diabetic patients. PMID- 2103726 TI - Optimized fluorometric determination of urinary delta-aminolevulinic acid by using pre-column derivatization, and identification of the derivative. AB - We previously reported the usefulness of a fluorometric method to determine urinary delta-aminolevulinic acid (ALA) concentrations by using post-column derivatization to monitor the effect of lead exposure. We have further improved the method by introducing pre-column derivatization by using reaction of ALA with acetylacetone and formaldehyde. Response of the hematopoietic system to lead exposure can now be easily detected at blood lead concentrations as low as 162 micrograms/L. The fluorescent ALA derivative, a new aromatic product, 2 methylideneamino-3,5-diacetyl-4,6-dimethylphenylpropionic acid, is separated on octadecyl silica column by high-performance liquid chromatography and the fluorescence intensity is detected with a fluorophotometer. Sample recoveries for 12 urine samples from workers exposed to lead and unexposed controls were 91.9 110.2%. The results obtained by the pre-column derivatization method agreed with those by the post-column derivatization method. The new method increases the sensitivity to a detection limit to 10 micrograms of delta-aminolevulinic acid per milliliter of urine and is simple enough to be used for routine monitoring of the biological effect of exposure to low concentrations of lead. PMID- 2103727 TI - Intravenous immunoglobulin therapy in systemic lupus erythematosus-associated thrombocytopenia. AB - Seven patients with thrombocytopenia and systemic lupus erythematosus were treated with intravenous (IV) doses of human immunoglobulin to assess clinical response and to examine the mechanism of action of IV immunoglobulin in these patients. Five of 7 patients had a greater than 50% increase in their platelet counts. Four of these patients had a sustained benefit of at least 6 months duration. The initial effectiveness of IV immunoglobulin therapy was not dependent on the reduction of levels of circulating platelet-binding IgG or circulating immune complexes. PMID- 2103728 TI - Attention deficit-hyperactivity disorder: is it a learning disability or a related disorder? PMID- 2103729 TI - A possible association of Ganser's syndrome and major depression. PMID- 2103730 TI - How wide is the clinical spectrum of the acrocallosal syndrome? Report of a mild case. AB - A boy presenting with an incomplete form of the acrocallosal syndrome is described. The syndrome shows clinical variability and it is stressed that none of the components is constant and facial dysmorphism is not always characteristic. PMID- 2103731 TI - Repair of calvarial nonunions by osteogenin, a bone-inductive protein. AB - Efforts were taken to determine the dose of bovine osteogenin (OG) that would induce more bone than that induced by 20 mg of rat particulate demineralized bone matrix (DBM), the amount allowed by the confines of an 8-mm rat craniotomy defect. Dose-response studies were performed for demineralized bone matrix alone and osteogenin, partially purified from bovine demineralized bone matrix, plus rat insoluble collagenous bone matrix (M). Demineralized bone matrix alone (2.5, 5.0, 10, 20, or 40 mg) or osteogenin (0.0625, 0.125, 0.250, 0.50, or 1.0 mg) plus 25 mg insoluble collagenous bone matrix was implanted into the pectoralis muscle for 3, 5, and 7 weeks. Both materials induced time- and dose-dependent formation of bone. The three highest dosages of osteogenin (plus insoluble collagenous bone matrix) induced more bone than 20 mg demineralized bone matrix and seemed to accelerate bone repair. However, when implanted into the 8-mm rat craniotomy defect for 4 weeks, 20 mg demineralized bone matrix and 0.5 mg osteogenin (plus insoluble collagenous bone matrix) induced comparable amounts of bone. These results suggest different mechanisms for bone formation in heterotopic and orthotopic sites. PMID- 2103732 TI - Should psychiatrists administer anesthesia for ECT? AB - Whether psychiatrists are qualified to give anesthesia for ECT is controversial. At the authors' hospital, over a 9-year period ECT resulted in no mortality and minimal morbidity; in 98.8% of the treatments, anesthesia was given by psychiatrists. The average nursing time required for cases in which anesthesiologists administered anesthetic was longer than that for psychiatrists' cases. This difference may be related to succinylcholine dose and efficacy of ECT. The authors' surveys indicated that psychiatrists and anesthesiologists have differing opinions on whether psychiatrists should administer anesthesia for ECT and that few psychiatry residency programs which teach ECT provide training in anesthesia. PMID- 2103734 TI - Histological identification of Helicobacter pylori in early and advanced gastric cancer. PMID- 2103733 TI - B-cell activation and HIV-1 infection: deeds and misdeeds. PMID- 2103735 TI - Psychiatric illness and irritable bowel syndrome: a comparison with inflammatory bowel disease. AB - Structured psychiatric interviews and psychological self-report measures were administered to 28 patients with irritable bowel syndrome and 19 patients with inflammatory bowel disease. Significantly more of the patients with irritable bowel syndrome had lifetime diagnoses of major depression, somatization disorder, generalized anxiety disorder, panic disorder, and phobic disorder. They had significantly more medically unexplained somatic symptoms, and most had suffered from psychiatric disorders, particularly anxiety disorders, before the onset of their irritable bowel symptoms. PMID- 2103736 TI - Screening for carriers of cystic fibrosis among partners of people heterozygous for the disease. PMID- 2103737 TI - Safety and health in the construction industry. PMID- 2103738 TI - Juniors' hours. PMID- 2103740 TI - Unresolved grief. PMID- 2103739 TI - Retinal haemorrhages. PMID- 2103741 TI - Pathological jealousy and pimozide. PMID- 2103742 TI - Risk factors of female HIV-seropositive patients attending the clinic for sexually transmitted diseases at St Mary's Hospital, London. AB - Of 3450 women tested for antibodies to human immunodeficiency virus HIV-1 and HIV 2 between September 1985 and July 1989, 61 were positive (1.8%). Twenty-seven of these (44%) were presumed to have acquired their HIV infection by heterosexual contact and 23 (38%) were intravenous drug addicts. In geographical origin, 23 (38%) of the patients were from the UK and 19 (31%) from Africa. Amongst these 61 women, 2 (3%) have since died, one committed suicide and one was suspected of committing suicide. PMID- 2103743 TI - Episodic prolactin release after removal of dopamine inhibition in vitro. AB - Prolactin (PRL) release following the removal of tonic dopamine (DA) inhibition was investigated in superfused cultures of dispersed rat anterior pituitary cells. The removal of DA (500 nM) inhibition resulted in a rapid and sustained increased in PRL release as measured by RIA which occurred in an episodic manner. The first PRL pulse reached a maximum 15 to 30 min. after DA removal (20.6 +/- 1.1 min). The second pulse occurred 40 to 45 min. after DA removal and the mean interpulse period was 21.7 +/- 1.2 min. The amplitude of the first pulse was 1.6 to 13.5 higher than the value observed in the presence of DA. It was followed by a nadir that was 1.1 to 8.0 fold higher than the basal value. The second pulse was of slightly lower amplitude, reaching a maximum of 2.3 to 8.0 fold over the control value and 1.25 to 2.5 fold over the preceding nadir. This episodic pattern was observed in 16 independent experiments performed with cells cultured at a density of 0.7-2.8 x 10(6) cells/coverslip. We hypothesize that lactotrophs in vitro have an inherent 20 minute secretory rhythm as has been observed under certain circumstances in vivo. Tonic dopamine inhibition restrains the otherwise random secretory rhythms of lactotrophs thereby synchronizing the secretory phase of the cells upon its removal. Consistent with this hypothesis episodic PRL release was not observed when DA was constantly present or absent. PMID- 2103744 TI - Over-reinforcement protects against memory deficits induced by muscarinic blockade of the striatum. AB - It has been shown that blockade of muscarinic receptors of the anterior striatum (AS) induces significant impairments in the retrieval of stored information of a passive avoidance task, trained with conventional parameters of footshock, and that the same blockade is ineffective in altering short-term memory of this task. The results of the present experimental series showed that in conditions of over reinforcement, microinjections of scopolamine into the AS shortly after training or before retention testing of passive avoidance, do not produce memory deficits when retention is assessed 30 min, 24 h or 48 h after training. It is suggested that after an enhanced learning experience (over-reinforcement) striatal cholinergic activity is not involved in short- and long-term memory functions. PMID- 2103745 TI - Histology of rat placentas treated with methylhydrazine Ro 4-6467. AB - The placenta is a vascular organ within the uterus, connected to the fetus by the umbilical cord; it is the structure through which the fetus is nourished. In the rat placenta, three regions can be identified: the decidua basalis, the basal zone, and the labyrinth. In the present work, doses of 4.2 mg/kg of Natulan (Roche), as used for human therapy, were administered orally to pregnant rats. The number of glycogenic cells from the basal zone of the placenta was increased, which allows us to suggest that Natulan causes an inhibition of glycolysis, by blocking the metabolism of the placenta, as proposed by Warburg. PMID- 2103746 TI - Cortisol reactivity and cognitive performance in a continuous mental task paradigm. AB - The after-effects of fatigue or stress on the performance of cognitive tests have been particularly difficult to demonstrate. In this study we examined whether salivary cortisol, used as an index of stress evoked by the continuous performance of mental tasks, reflected individual differences in cognitive performance. In a within-subject experiment in which 24 subjects were exposed to 4 hours of continuous mental activity and to a control session, significantly higher cortisol levels were found during the continuous task session. Cognitive performance was assessed before and after each session. The relevant test parameters involved aspects of verbal memory, concept shifting and divided attention. When subjects were divided into two groups based on the magnitude of individual cortisol responses to the continuous tasks, it was found that the subgroup with higher cortisol responses decreased in attention compared with their attention after the control session. In contrast, the performance of the subgroup with no or lower cortisol responses did not differ between the two sessions. There was no evidence of similar effects on verbal memory or concept shifting. PMID- 2103747 TI - P300 and time of day: circadian rhythms, food intake, and body temperature. AB - The P300 or P3 component of the event-related brain potential (ERP) was obtained from five groups of 24 young adult subjects, with each group measured at a different time of day (8 a.m., 11 a.m., 2 p.m., 5 p.m., 8 p.m.). An activity preference questionnaire was used to ensure that an equitable number of morning- and evening-preferring subjects were obtained for each testing time. P3 measures, physiological (body temperature, heart rate, subjective alertness), and cognitive performance (digit span, prose memory, digit symbol) variables were assessed. P3 amplitude and latency were not affected directly by the time of day. However, P3 amplitude was smaller in subjects who had not eaten within 6 hours of testing relative to subjects who had a recent meal, and P3 latency was correlated negatively with body temperature. The findings suggest that although the P3 ERP is not influenced by circadian rhythms, it is related to recency of food intake and physiological factors which change with time of day. PMID- 2103748 TI - Facial electromyographic reactions and autonomic activity to auditory stimuli. AB - This study explored whether high- and low-intensity auditory stimuli evoke different facial electromyographic reactions and autonomic responses. Subjects were repeatedly exposed to 95-dB and 75-dB tones (1000 Hz, 40 ms rise and fall times) while their facial electromyograms from the corrugator and zygomatic muscle regions, heart rate, skin conductance responses, skin conductance half recovery time and ratings were measured. The 95-dB tone evoked a "negative" reaction with increased corrugator activity and an autonomic response pattern that carried aspects of a defense reaction, that is, slowly habituating skin conductance responses with retarded recovery rate and an initial tendency to heart rate acceleration. Furthermore, the 95-dB tone was rated as unpleasant. The 75-dB tone elicited an orienting response indicated by a distinct heart rate deceleration and fast habituating skin conductance responses with a relatively short recovery time. Thus, the present study demonstrated that the facial electromyographic technique is sensitive to simple environmental stimuli such as auditory stimuli and that the facial response is consistent with the autonomic response patterns and the experience of the stimuli. PMID- 2103749 TI - The vascular orienting response and the law of initial values. AB - Vascular responses following exposure to the experimental situation (a type orienting reflex) were evaluated in 6 male subjects. Bilateral skin temperature was recorded from the head and finger regions for the duration of the experimental session. The interaction of Location X Trial (p less than or equal to 0.002) showed reliable differences between the head and finger sites and the left and right forehead sites early in the session followed by differential rates of change during the session across sites. The results support the recent claim for the importance of the law of initial values in finger temperature research and extend the findings to multiple site comparisons in the absence of hemispheric task demands. The vascular orienting reflex to the experimental context may augment initial value differences among recording sites. PMID- 2103750 TI - Comparisons of the nonlinear dynamics of electroencephalograms under various task loading conditions: a preliminary report. AB - Comparison of the characteristics of electroencephalogram (EEG) records treated as realizations from a nonlinear process were compared under four different conditions: eyes shut resting, and three silent observation instructions to predict the patterns of randomly generated lights which illuminated every 10 seconds. The correlation dimension of the EEG was calculated by a method involving finding the correlation integral in m-dimensional space, and found to show some variations within time series. The degree and directions of changes in the dimensionality of the process varied between observers and did not clearly confirm some earlier reported findings, but it is demonstrable that the measures of nonlinear brain dynamics can be correlated with psychological variables. Reasons for this are discussed. PMID- 2103751 TI - Review article: treatment of the gastrointestinal manifestations of AIDS. AB - The Acquired Immune Deficiency Syndrome (AIDS) is frequently associated with infections, infestations, or diseases of the gastrointestinal tract. This review describes the practical aspects of treating oral and oesophageal disease, the management of weight loss and diarrhoea, the role for zidovudine, and the management of Kaposi's sarcoma. PMID- 2103752 TI - Effect of propranolol on secretin-induced gastrin release and secretin-induced tachycardia in patients with the Zollinger-Ellison syndrome. AB - The mechanism for secretin-induced gastrin release in the Zollinger-Ellison syndrome is uncertain. We evaluated whether the stimulatory effect of intravenous secretin on gastrin release was partly mediated through a beta-adrenergic stimulatory mechanism. Serum gastrin concentrations and heart rate were monitored in six patients with the Zollinger-Ellison syndrome. Secretin (2 clinical units/kg) increased mean serum gastrin concentrations from 1558 pg/ml basally to a peak of 3683 pg/ml (136% above baseline). This increase was not altered by pretreatment with 2 mg of propranolol intravenously, a dose which in previous studies blocked terbutaline-induced gastrin release. Secretin increased heart rate by 14 beats/min (20% above base-line) and this also was not altered by propranolol pretreatment. Thus, the stimulatory effects of secretin on gastrinoma cells and the heart do not appear to be mediated by beta-adrenergic receptors. PMID- 2103753 TI - Rectal bismuth subsalicylate as therapy for ulcerative colitis. AB - In a prospective open study, 15 patients with ulcerative colitis which was unresponsive to conventional therapy were treated with enemas containing bismuth subsalicylate (700 or 800 mg b.d.). Nine out of the 15 patients showed a significant clinical response, and 6 had gone into complete clinical remission after 8 weeks treatment. Sigmoidoscopoic appearances of the rectal mucosa showed improvement in 9 out of 15 patients at 2 weeks, and 11 out of 15 at 8 weeks. The mucosa appeared sigmoidoscopically normal in 6 out of 15 at 8 weeks. It proved possible to reduce the oral prednisolone dosage from a median of 15 mg/day (range 10 to 35 mg/day) to 6 mg/day (range 0 to 18 mg/day) after 8 weeks of treatment; 5 patients were no longer taking oral steroids at this time. Rectal bismuth subsalicylate appears likely to be an effective therapy in ulcerative colitis and controlled trials are now required. PMID- 2103754 TI - Long-term maintenance treatment of gastric ulcers with ranitidine. AB - One hundred and twenty patients with gastric ulcer disease, who had been receiving maintenance treatment with ranitidine (150 or 300 mg/day) for periods up to 7 years, were studied retrospectively. The proportion of patients remaining free from symptomatic recurrence of ulcer during maintenance treatment was 97% after 1 year; 90% after 3 years; and 79% after 5 years. No patient developed haemorrhage or perforation during maintenance treatment. None of the demographic features was shown to be associated with a significantly increased risk of ulcer recurrence during maintenance treatment. Comparison of the recurrence rates during maintenance treatment with those during periods without active anti-ulcer therapy, using life table and incidence density analysis, showed a significant difference in favour of maintenance treatment. We conclude that maintenance treatment with ranitidine for 5 years significantly reduces the risk of symptomatic ulcer recurrence in patients with gastric ulcer. PMID- 2103755 TI - Antioxidant therapy for recurrent pancreatitis: placebo-controlled trial. AB - Oxidant stress has been proposed as the initiating pathogenetic mechanism in pancreatitis, hence micronutrient antioxidant therapy has been assessed in patients with recurrent attacks and/or constant pancreatic pain. In a 20-week double-blind double-dummy crossover trial active treatment was given as two types of tablets providing daily doses of 600 micrograms organic selenium, 9000 IU beta carotene, 0.54 g vitamin C, 270 IU vitamin E and 2 g methionine. Of 28 patients enrolled, 20 adhered to the full protocol (idiopathic chronic 8, alcoholic chronic 7, idiopathic acute 5). Six patients had an attack whilst on placebo but none whilst on active treatment (P = 0.032). Analysis of visual analogue scoresheets to compare background pain in the 10-week period before entry and during each phase of the trial, using a 10-cm scale for each of 11 best descriptors, endorsed the beneficial effect of active treatment (placebo v baseline, P = 0.073; active v baseline, P less than 0.001; active v placebo, P = 0.049). The same trend emerged from analysis of pain-score diaries by conventional and time series methods. Micronutrient antioxidant therapy thus offers a new approach to the treatment of recurrent (non-gallstone) pancreatitis and/or pancreatic pain. PMID- 2103756 TI - Gastric histology and plasma gastrin response to a meal in patients with duodenal ulcer disease after five years treatment with ranitidine. AB - Fifty asymptomatic patients with duodenal ulcer disease, aged 31-82 years, who had received ranitidine maintenance therapy continuously for five or more years without a symptomatic recurrence, were studied. Fasting plasma gastrin concentrations were normal (mean 24 pmol/L, S.D. +/- 22) while the post-prandial gastrin response was variable with maximum plasma concentrations ranging from 16 to 309 pmol/L. Endoscopy revealed six asymptomatic peptic ulcers. Histological examination of gastric biopsies showed mild, superficial inflammatory cell infiltration of the fundic mucosa, but more extensive inflammatory cell infiltration with some atrophy of the mucosal glands in the antral mucosa. Patchy intestinal metaplasia was evident in the antral mucosa of 18 patients. No fundic ECL cell hyperplasia was seen. Helicobacter pylori were detected in the corpus and antrum of most patients. These results suggest that maintenance treatment with ranitidine for 5 years is not associated with either significant hypergastrinaemia or with changes in the fundic mucosa which could be interpreted as pre-malignant. PMID- 2103757 TI - Bolus or slow titrated injection of midazolam prior to upper gastrointestinal endoscopy? Relative effect on oxygen saturation and prophylactic value of supplemental oxygen. AB - A total of 131 patients undergoing upper gastrointestinal endoscopy were sedated with midazolam given as a bolus injection over 5 seconds. The oxygen saturation was continuously measured using a pulse oximeter. Supplemental oxygen was given via nasal cannulae at a rate of 3 litres per minute to 54 patients, while the remaining 77 patients only received oxygen if their oxygen saturation dropped below 85%. Both groups in the present series were compared with 3 previously published series of patients, in whom we had used intravenous midazolam as a slow titrated injection. Despite using on average only two-thirds of the dose of midazolam, following bolus injection the degree of oxygen desaturation during the endoscopic procedure was greater, and the ability of supplemental oxygen delivered via nasal cannulae to prevent hypoxia was less (P less than 0.01), than with a slow titrated injection. PMID- 2103758 TI - Duodenal ulcer healing and acid secretory responses to modified sham feeding and pentagastrin stimulation. AB - The effect of duodenal ulcer healing on the acid secretory responses to modified sham feeding and maximal pentagastrin stimulation has been studied in 17 patients treated successfully with ranitidine (n = 9) and sucralfate (n = 8). Parietal cell sensitivity was calculated as the ratio of the modified sham feeding response to the peak pentagastrin response, expressed as a percentage. Ulcer healing after sucralfate therapy resulted in significant falls in modified sham feeding stimulated acid output (P less than 0.02), from 9.4 (1.8-17.0) (median + range) to 3.7 (0.2-9.4) mmol/h; in peak acid output (P less than 0.05) from 42.8 (23.0-61.4) to 27.7 (7.2-51.0) mmol/h; and in the parietal cell sensitivity (P less than 0.05) from 19.2 (4.4-42.6) to 14.3 (2.8-19.7)%. No significant falls in any of these parameters were noted following ulcer healing with ranitidine. Duodenal ulcer healing with sucralfate results in decreased acid secretory responses to vagal and pentagastrin stimulation. PMID- 2103759 TI - Efficacy of diltiazem in the treatment of diffuse oesophageal spasm. AB - Calcium antagonist relax smooth muscle, a possible useful concept in treatment of diffuse oesophageal spasm. Therefore the effects of oral diltiazem (60 mg t.d.s.) and placebo were compared in eight patients with diffuse oesophageal spasm in a 10-week double-blind crossover study. The patients recorded the severity of chest pain and/or dysphagia in daily pain diaries using visual analogue scales. Chest pain index and dysphagia index were calculated by multiplying frequency with daily intensity of each individual symptom. When compared to placebo, diltiazem did not significantly change the overall dysphagia index and chest pain index. An individual sizeable reduction of dysphagia was attained on diltiazem in four out of six patients and in six out of eight patients suffering from chestpain. Side effects were not seen during diltiazem therapy. Diltiazem, in our study, did not yield in a significant improvement of symptoms in diffuse oesophageal spasm. Diltiazem, however, can offer relief in selected individual patients suffering from diffuse oesophageal spasm. PMID- 2103760 TI - Effect of mefenamic acid on bowel transit time in healthy adult volunteers. AB - The effect of mefenamic acid on bowel transit time was investigated. Seven healthy adult male subjects of age 39 +/- 2.4 years (mean +/- S.E.M.) received placebo or mefenamic acid (500 mg t.d.s) orally in randomized order for five days, with a 7-day washout between studies. On the third morning after starting the drug they had a meal containing Redi-Brek and baked beans with radio-opaque markers. Small bowel transit time was measured using breath hydrogen, and whole gut transit time was measured using radio-opaque markers. The small bowel transit times were 160 min (median) with placebo and 50 min with mefenamic acid (P less than 0.05). The percentages of appearance of marker in stool within 24 h were 24.9 +/- 11.8 (mean +/- S.E.M.) with placebo and 48.9 +/- 11.7 with mefenamic acid (P less than 0.05). The times of appearance of twenty-fifth marker in stool were 41.0 +/- 4.4 h with placebo and 26.9 +/- 3.2 h with mefenamic acid (P less than 0.05). The total weights of faeces in 72 h were 500.9 +/- 96.2 g with placebo and 657.1 +/- 118.8 g with mefenamic acid (P less than 0.05). Mefenamic acid in therapeutic doses (500 mg t.d.s.) accelerated bowel transit time in healthy subjects. PMID- 2103761 TI - Short report: sedation for upper gastrointestinal endoscopy--diazepam versus midazolam. AB - Intravenously injected midazolam was associated with a greater degree of sedation, as assessed by 24-h retrograde amnesia, than the longer acting benzodiazepine, diazepam. No differences in the frequency of pain on injection or the occurrence of venous sequelae were noted between the two preparations. PMID- 2103762 TI - [Hypothyroid myopathy]. PMID- 2103763 TI - [Hypothyroid myopathy. Clinico-pathologic study of 20 cases]. AB - 20 patients afflicted with primary hypothyroidism were studied in order to evaluate the association of clinical or sub-clinical myopathy, detected by neurophysiological (electromyography) (EMG) or neuropathological methods (muscular biopsy with enzymatic study). 70% of the patients had muscular weakness (moderate in 30% and severe in 40%) of the scapular and pelvic muscles. 60% of the patients had muscular cramps. There was no myodema nor muscular atrophy or hypertrophy. Seric CPK was high in 70% of the cases. EMG was myopathic in 65%. All cases with weakness registered EMG alterations. The histological findings were import findings were important. The enzymatic techniques showed alterations of the fiber subtypes in 90% of the cases. The type I fibers had sarcolemmal and mitochondrial accumules in 85% and 70% had areas without oxidative activity, similar to "core". In this study, we did not find any correlation between the evolution time of hypothyroidism, hormonal levels, CPK increase, and muscular weakness. The EMG was myopathic in cases with severe weakness, however, in patients with moderate weakness it could also prove abnormal. There was no correlation between the electric myopathic pattern, CPK levels and thyroid hormones. PMID- 2103764 TI - [Thyroid myopathy. Effect of treatment with thyroid hormones]. AB - We studied 20 patients afflicted with primary hypothyroidism and treated with thyroid hormone replacements, with the aim of evaluating the clinical, biochemical, EMG and anatomo-pathological effects. Cramps, as well as subjective and objective proximal muscular weakness, disappeared. Seric CPK was normalized in all cases after 1-8 weeks of treatment. EMG myopathic patterns faded away in all cases. Anatomopathological changes took longer to observe; 5 cases with new biopsy showed an isolate atrophy of type II fibers, one of them after 18 months in treatment; type I fibers had mitochondrial accumula without change compared to the initial biopsy. There was a clear tendency for the destroyed fibers to become normalized and for the structures similar to the "core" to vanish. PMID- 2103765 TI - [Colorectal cancer: retrospective analysis of 762 cases]. AB - A study carried out during 1976-1988 on patients with colorectal cancer revealed an increase in the incidence of this disease of 150%, with a sex ratio of 1:1.17, there being a slight predominance in males. In the patients studied, 3.41% were older than 40. In patients in the 60-70 age group, 63.4% of the cases were diagnosed. The most frequent location of the tumor is the rectum (24.4%) and the least frequent (1.57% and 1.04%, respectively) in the hepatic and splenic angles. This was observed in all the years comprising the study. Adenocarcinoma was the commonest type of tumor, there being a highly significant association (p less than 0.001) between the histological type of cancer and the state of infiltration observed at the time of diagnosis. PMID- 2103766 TI - [HLA antigens in patients with rheumatoid arthritis, their relatives, and spouses]. AB - The results of the comparison between phenotypic frequency of HLA antigen classes I and II in patients afflicted with rheumatoid arthritis (RA) and their relatives (study carried out in the east of Andalusian), showed a significant increase of HLA A24, B51, B44, CW1 ans CW5 class I antigen in the group of relatives. We found a statistically significant DR4 antigen class II increase in both, patients and relative groups. The marriage parther of patients with RA did not have variations in class I or II HLA antigens compared to the control group. We concluded that RA is probably related to the following antigens: A24, B51, B44, CW1, CW5 and DR4. PMID- 2103767 TI - [Staphylococcus aureus bacteremia at a general hospital]. AB - 70 cases of bacteremia caused by Staphylococcus Aureus were studied. 49 (70%) males, and 21 (30%) females; 45 (64.5%) cases being nosocomial and 25 (35.4%) community acquired. The complications were significantly associated to the community acquired bacteremia (p less than 0.001), endocarditis and cutaneous abscesses being the most frequent (4). The group of cases with rapidly lethal prognosis was significantly associated to an increase of mortality (p less than 0.001), while lethal and non-lethal groups showed a decrease in mortality (p less than 0.001). We did not find a statistically significant association between nosocomial and community acquired bacteremias nor between antibiotic therapy and the mortality rate, chi 2 = 1.747.303 (N.S.), chi 2 = 1.323.806 (N.S.). PMID- 2103768 TI - [Two cases of massive pulmonary embolism associated with estrogen intake. Diagnostic and therapeutic usefulness of pulmonary angiography]. AB - Two cases of massive pulmonary embolism observed in patients under estrogen therapy, are presented. We describe the clinical findings, highlighting the value of the arteriography in the diagnosis and the use of fibrinolytic therapy, being successful in both cases. PMID- 2103769 TI - [Amyloid arthropathy associated with multiple myeloma]. AB - Amyloidosis as a complication of patients afflicted with multiple myeloma only arose in 15% of the cases. The articular localization is particularly rare, the clinical findings being similar to rheumatoid arthritis. A case of amyloid arthritis associated to Bence-Jones myeloma, kappa type, is presented and the literature is reviewed. PMID- 2103770 TI - [Spleen abscess]. AB - 3 cases of splenic abscess (SA), all of them with similar clinical findings; abdominal pain, liver and splenic enlargement and leukocytosis, are presented. The diagnosis was suspected by abdominal ultrasound and confirmed by CTR. We focused the interest on the etiopathogenesis, diagnosis and the rareness of the bacteria isolated: Salmonella group D (two cases) and Bacteroides Fragilis. PMID- 2103771 TI - [Human immunodeficiency virus infection in the Spanish population. Review of the literature]. AB - The epidemiological aspects of the infection by the human immunodeficiency virus, HIV, in the Spanish population as described in the literature are reviewed. From the published studies is evident that HIV infection is limited to the population risk groups established in the epidemiological world reports, heroin addicts, homosexuals, heterosexuals with sexual contacts with infected persons and blood and hemoderivates receptors. The observed frequencies in these risk groups are similar to that described in other countries. PMID- 2103772 TI - [Value of regular exercise in medicine]. PMID- 2103773 TI - [Calcium pidolate and bone metabolism parameters]. PMID- 2103774 TI - [Obliterative bronchiolitis with organizing pneumonia: presentation of a case with unusual radiologic characteristics]. PMID- 2103775 TI - [S. aureus multiple osteomyelitis after prolonged latency period]. PMID- 2103776 TI - [Adult Schonlein-Henoch syndrome with abdominal involvement refractory to steroid treatment]. PMID- 2103777 TI - [Rhabdomyolysis associated with Salmonella enteritidis infection]. PMID- 2103778 TI - [Diagnosis of Behcet's disease. Which criteria should be used?]. PMID- 2103779 TI - [Alcohol withdrawal syndrome]. PMID- 2103780 TI - [Alcohol withdrawal syndrome at the internal medicine department of a general hospital; epidemiology and hospital costs]. AB - Alcohol withdrawal syndrome (AWS) is an admission problem and can also occur in hospitalized patients. We endeavoured to ascertain the exact epidemiology and hospital cost of AWS based on a review of the charts of patients admitted during 1986, 1987, 1988 (total = 78). The statistical analysis of the differences was performed by chi-square test with a significant level = or less than of 0.05. The results were: total hospital prevalence of AWS = 2.44%, hospital prevalence by season = 3.33% (spring), 2.04% (summer), 2.28% (fall), 2.19% (winter). Outpatients presentation = 79.49%, highlighting fever syndrome of unknown origin (FSUO) (16.4%) and pneumonia (11.48%); hospital presentation = 20.51% focusing acute pancreatitis (31.25%) and pneumonia (25%) as first causes of admission. The significant association between FSUO and spring and winter (84.62%); relation male: female = 5.5: 1; mean age = 42.57 years; decade distributions = 1st decade 0%, second = 1.28%, third = 11.64%, fourth = 35.90%, fifth = 24.36%, sixth = 16.67%, seventh = 8.97%, eighth = 1.28%, ninth = 0%; mean admission time = 14.12 days; total hospital cost of out-patients presentation = 15.087.370 pesetas. PMID- 2103781 TI - [Intraerythrocyte levels of glucose-6-phosphate dehydrogenase in patients with essential arterial hypertension and persons with normal blood pressure. Modifications after nifedipine therapy]. AB - We evaluate the levels of intra-erythrocytes glucose-6-phosphate-dehydrogenase (G6PD) in a group of 50 patients with essential blood hypertension (EBH) (214.76 +/- 38.31 mU/ml) and in a group of 50 healthy persons (130.11 +/- 49.50 mU/ml) (p minor of 0.0005). At the same time, we have analysed the intraerythrocyte levels of G6PD of 34 healthy sons and daughters of hypertensive parents, detecting high levels in 13 of them. We observed a significant decrease of G6PD after the therapy with nifedipine in 20 hypertensive patients (p less than 0.0005). We conclude that measurement of G6PD enzyme activity can prove to be a good marker of essential hypertension. This change occurs at an early stage and is noticeable in high risk persons with family predisposition. It is possible to modify levels by working on cation changes through membrane cells by calcium-antagonist. PMID- 2103782 TI - [Serum levels of lipids, lipoproteins and apoproteins (A, A-1, and B) in diabetes mellitus type I. Their relationship with the degree of metabolic control]. AB - We studied the role played by an adequate metabolic control on lipids, lipoproteins, apolipoprotein A (apo A), apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B), in 30 type I diabetic patients at different states of the diseases. We did not observe significant differences, comparing the mean values of lipids and lipoproteins, in the group of patients with good metabolic control. Patients, without appropriate diabetic control, showed values significantly higher in triglycerides and VLDL-C and significantly lower in HDL-C compared to the values of the control group. In respect of the apoprotein pattern, we did not observe significant differences between controlled diabetic patients; while non-controlled diabetic patients showed mean values higher of apo B, but no differences between apo A and apo A-I. Our results support the previous evidence published by other authors, confirming the relationship between an adequate diabetic control and the onset of lipoprotein changes, that can play a causal role in arteriosclerosis. PMID- 2103783 TI - [Retrospective study of ulcerative colitis at an Andalusian hospital]. AB - We reviewed 96 cases of ulcerative colitis diagnosed during the period between 1970 and 1988, with the intention of analysing the presentation, complications, evolution and diagnosis aspects. The most frequent presentation symptoms were mucoid and bloody diarrhea (91.3%) and abdominal pain (84%), isolated rectal bleeding being predominated in distal type. The frequency of complications were 17.14%. X-ray findings were the lack of haustration and ulcers, the rate of normal barium enema being of 27.27% (without double contrast). Rectum was not affected in 6.8%. The endoscopy showed an edematous and congestive mucosa, ulcer with normal barium enema. The most significant anatomopathological findings were the lymphoplasmocyte and polynuclear infiltration of the proper lamina and epithelial ulcer, with a lack of cripta and absence of metaplasia of Paneth's cells. In our area, we have to use colonoscopy to diagnose the disease, because the double contrast barium enema is not performed as a routine. Only a few (5) of our patients needed surgical treatment. PMID- 2103784 TI - [Clinical patterns of selective IgA deficiency: 3 case reports]. AB - The selective deficit of IgA is characterised by its clinical variability. This disease can be detected in non-symptomatic patients or associated to multiple diseases of different features. The allergic reactions, recurrent infections, gastrointestinal alterations, autoimmune diseases, and some neoplasias are the most frequent features of this deficit. We present 3 cases with different pathology associated to the common deficit of IgA, giving a view of the wide clinical spectrum of this process. PMID- 2103785 TI - [Pneumothorax, Pneumocystis carinii, and AIDS]. AB - Spontaneous pneumothorax can be a complication of several pulmonary diseases, such as pulmonary emphysema, chronic bronchitis and interstitial pulmonary disease. Nevertheless, it is a rare complication of any pneumonia, there is no description of necrosis or abscess caused by Pneumocystis Carinii pneumonia. We present a case of spontaneous pneumothorax (which was not resolved), being a reason for admission, of a patient with AIDS who developed Pneumocystis Carinii pneumonia during the stay in hospital. We think that spontaneous pneumothorax can register bad evolution in patients with AIDS and pulmonary symptoms. PMID- 2103786 TI - [Esophageal tuberculosis and massive hematemesis]. AB - A patient with esophageal tuberculosis who died of massive hematemesis is described. The origin of the disease was probably pulmonary and the esophageal affliction could have been produced by both the ingestion of contaminated sputum or direct extension from mediastinal lymphatic nodes. The diagnosis was reached by the discovery of caseation granulomas at esophagoscopy and the isolation of Mycobacterium Tuberculosis in the sputum. We comment on the rareness of the disease, clinical and endoscopic features which can resemble a neoplasia. At the same time, we highlight the possibility of serious complications, mainly upper gastrointestinal hemorrhage which is potentially lethal, and the aorto-esophageal communication, thus early diagnosis and surgical treatment being most important. PMID- 2103787 TI - [Ileocecal and lymph node tuberculosis: a rare association in our area]. AB - A case of ileocecal tuberculosis associated to lymphatic nodes TB, is presented. This association is not frequently observed in all series and isolated cases registered in medical literature. In this particular case, we comment on the pathogenic problems of primary intestinal TB and the importance of the systemic clinical suspicion to diagnose this, nowadays, rare problem in our area. Finally, we discuss the value of certain diagnosis criteria related to the actual therapy, in which the conservative character is dominant, this therapy also being applied to post-surgical fistula in some individual cases such as the one presented here. PMID- 2103788 TI - [Selective deficiency of IgA]. AB - The selective deficit of IgA is the most frequently acquired immunodeficiency. It is important because of this and the variability of the clinical presentation, which might be non-symptomatic or simply show several clinical features. The prognosis depends on the associated clinical affliction. There is no substitute treatment for this immunodeficiency, in which the immunoglobulins administration produces a paradoxical antibody formation against this, and adverse immunological reactions. We reviewed the immunodeficiency in this paper, highlighting the frequency, pathogenia, clinical diversity and therapy. PMID- 2103789 TI - [Insulin and atherogenesis]. PMID- 2103790 TI - [Hepatotoxicity caused by erythromycin ethylsuccinate]. PMID- 2103791 TI - [Gingival hyperplasia induced by nifedipine]. PMID- 2103792 TI - [Macleod's syndrome. A case report]. PMID- 2103793 TI - [Temporal arteritis with intradural involvement of the cranial arteries]. PMID- 2103794 TI - [Tetany and hypokalemia. Importance of ionized calcium measurements]. PMID- 2103795 TI - [Eosinophilia induced by heparin: a new case]. PMID- 2103796 TI - [Laryngeal carcinoma, testicular neoplasms and non-Hodgkin's lymphoma. A new case of multiple primary neoplasms]. PMID- 2103797 TI - [Clinical considerations on community-acquired pneumonia]. PMID- 2103798 TI - [Microbiologic diagnosis of community-acquired pneumonia]. PMID- 2103799 TI - [Treatment of community-acquired pneumonia]. PMID- 2103800 TI - [Streptococcus pneumoniae pneumonia]. PMID- 2103801 TI - [Pathogenesis of community-acquired pneumonia]. PMID- 2103802 TI - [Legionella pneumophila pneumonia]. PMID- 2103803 TI - [Bacterial pneumonia in patients with human immunodeficiency virus infection]. PMID- 2103804 TI - [Hospital pneumonia]. PMID- 2103806 TI - [Information in primary care]. PMID- 2103805 TI - [Etiology of community-acquired pneumonia]. PMID- 2103807 TI - [The care of the terminal patient as viewed by the family physician]. AB - We made a survey among physicians of primary care teams (PCT) from Vizcaya to assess their opinion about the care of the patient with cancer in the terminal period. A total of 85% of the surveyed physicians responded; 70% considered that the care given was inadequate; 90% thought that the patients wishes to die at home. 50% felt that the patient should know the diagnosis, although 85% believed that it was virtually always unknown to him in practice. The most commonly found symptoms were anorexia, asthenia, pain, depression and anxiety, which resulted in serious management difficulties for 25-45% of physicians. 65% were assisted by nurses. The participation of the rest of the team and of specialists was irrelevant. Most felt frustration (59%) and dissatisfaction (78%) with those patients. The physicians find great difficulty to communicate with the patient, and need more information, training and cooperation. Is should be clear that the aim is the well being of the patient, thus diminishing the frustration of the professionals. PMID- 2103808 TI - [The evaluation of different methods for rapid diagnosis in the detection of asymptomatic bacteriuria in pregnant women]. AB - We compared the effectiveness of different methods of rapid diagnosis in the detection of asymptomatic bacteriuria in 74 females during the first trimester of pregnancy. The sensitivity, specificity and negative predictive value for the visual reading of nitrites, leukocyte sterase, bacteriuria and leukocyturia in the sediment and bacteria in Gram stain were 77%, 22%, 33%, 22% and 88%, 98%, 85%, 82%, 91% and 86%, and 97%, 89%, 90% and 90%, with and accuracy of 96%, 77%, 76%, 82% and 86%, respectively. The combination of visual readings of nitrites and Gram stain showed a sensitivity and negative predictive value of 100%. We conclude that if the reading of the reactive strip is negative, the likelihood of a positive culture is very small, and it is minimal when combined with Gram stain. PMID- 2103809 TI - [The usefulness of the annual electrocardiogram in arterial hypertension follow up]. AB - We evaluated the usefulness of ECG in the follow up of 223 hypertensive patients included in a program for the control of hypertension. Yearly ECG was requested in 84.3% of the evaluated patients. Its interpretation resulted in therapeutic changes in 6 patients. The agreement of the interpretation of 122 ECG tracings between the primary care team and a cardiologist was moderate. General practitioners overrated normality (87 versus 69 cases), and underdiagnosed left ventricular hypertrophy (6 versus 10 cases) and ischemic heart disease (6 versus 17 cases). Half of the diagnoses of ischemic heart disease made by the general practitioner were not accepted by the cardiologist. The compliance with a protocol does not guarantee a higher quality of care. PMID- 2103810 TI - [Anemia in the pregnancies followed-up at a health center]. AB - We retrospectively evaluated the 134 pregnancies which were controlled in our health center in a 4-year period, so as to evaluate anemia in pregnancy and the factors influencing its development. In the study sample, 18.65% of the women had anemia. The age did not have any influence on the hemoglobin and packed red cell volume at the beginning of pregnancy, but it had at the end (p less than 0.01). He types of anemia were classified, and the normocytic-normochromic was the most common (68%). The investigations carried out for the etiological characterization of the anemias, the treatments and their results were evaluated. A lack of homogeneity in treatments, a small efficacy (32%), and a lack of specific investigations for the etiological evaluation were found (24%). Guidelines for the investigation and therapy of anemia during pregnancy are suggested. PMID- 2103811 TI - [The indicators of the quality of the prescription for chronic pathologies]. AB - To assess the qualitative characteristics of the prescription for chronic diseases and to select the most appropriate quality indicator, we evaluated 1588 drugs recorded in 549 forms for chronic prescription. 64.9% of the drugs were included in the Index Farmacologic, and the same rate in the Essential Drugs list of the WHO, 73.4% had a high intrinsic value (IV) and 80.7% were monocomponents. The male patients received more drugs included in the WHO list and with high IV, while patients older than age 65 years received more drugs with absent or unacceptable IV. A higher quality in the four indicators was found in the prescriptions from the CAP physicians than in those from specialists. The drug preparations with a not high IV more commonly prescribed belonged to the categories of cerebral and peripheral vascular therapy (16.2%), antacids and antiflatulents (9.3%), oral antidiabetics (8.4%), and antivaricose and antihemorrhoidal drugs (8.4%). It is concluded that the intrinsic value in the most adequate quality indicator for the prescription studies in primary care. PMID- 2103813 TI - [Splenomegaly]. PMID- 2103812 TI - [Autosomal dominant polycystic renal disease: a study of 5 familial cases]. AB - Dominant autosomal polycystic renal disease (DAPRD) is the most common cystic nephropathy, with multiorgan expression in many cases. Chronic irreversible renal failure is its major complication. Its clinical presentation is variable and it may remain symptom-free; therefore, it is important to know its many renal and extrarenal features which may suggest the diagnosis together with the family history, and also indicate the diagnostic and therapeutic possibilities. The primary care physician may also play a role in prevention, with the early diagnosis of the involved patients and genetic counseling with information of the implications. We report 5 cases of DAPRD with a clinical evaluation and family study, and also a succinct literature review. PMID- 2103814 TI - [Supraventricular arrhythmias]. PMID- 2103815 TI - [Methods of investigation: bibliography with comments (II)]. PMID- 2103816 TI - [An attitude study and tabagism of health center personnel]. PMID- 2103817 TI - [The human immunodeficiency virus and heterosexual transmission]. PMID- 2103818 TI - [The evaluation of requests for emergency consultations in primary care]. PMID- 2103819 TI - [Spontaneous pneumomediastinum: the importance of a systematic physical examination]. PMID- 2103820 TI - [Epidemic outbreaks of hepatitis A and its control]. PMID- 2103821 TI - [The etiology and resistance of extrahospital urinary infections]. PMID- 2103822 TI - [The genogram in family medicine]. PMID- 2103823 TI - [The importance of the early diagnosis of the association of tuberculosis and human immunodeficiency virus infection]. PMID- 2103824 TI - [A cost study of amoxicillin treatment. The commercial packaging versus the clinical packaging]. PMID- 2103825 TI - Molecular biology of the factors responsible for Yersinia virulence. PMID- 2103826 TI - The use of synthetic peptides in the diagnosis of HIV infections. AB - The antigenic structure of HIV proteins was analyzed semiempirically. Peptides mimicking fragments of the main structural HIV-1 proteins (p17, p24, gp41, and gp120) were selected and synthesized, with account taken of the level of conservation of various HIV genome fragments. The synthesized peptides were then subjected to immunological study with human sera in an enzyme-linked immunosorbent assay (ELISA). Peptides from two regions were found to be particularly immunoreactive with sera from HIV-1 infected persons: the C-terminal end of gp120 and a sequence approximately sixty to eighty amino acids in from the N-terminus of gp41. In fact, more than 96% of HIV-1 positive sera reacted with peptide 495-516 of gp120 (SP-III), peptide 584-602 of gp41 (LS-19), and peptide 601-616 of gp41 (SP-15). Additionally, twelve out of twelve serum samples from Ugandans infected with HIV-1 reacted with both SP-III (from HTLV-III) and SP-29 (gp41, 598-609; from the LAV-ELI isolate), suggesting that these immunodominant sites are useful diagnostically irrespective of the infecting isolates. HIV-2 peptides were also synthesized, and immunoreactivity and cross-reactivity examined. Only two peptides (581-603 of gp32 and 592-605 of gp32) reacted with all of the six HIV-2 positive sera tested. These peptides did not react with HIV 1 positive sera or control sera from healthy blood donors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103827 TI - Ionic cyclotron resonance in biomolecules. AB - The possible mechanism of action of weak electric and magnetic fields of extremely low frequency on biomolecules is discussed in terms of the resonance effects on the precession of the ion orbits in a static magnetic field. The proposed model retains the principal merits of the familiar model of Liboff, but is free from the basic shortcomings of the latter. PMID- 2103828 TI - Enantiomeric and diastereoisomeric analysis of nonproteinogenic methyl and hydroxy amino acids. AB - The enantiomeric and diastereoisomeric analysis of nonproteinogenic methyl and hydroxy amino acids, obtained by asymmetric synthesis with the aid of a chiral regenerable reagent, has been carried out by liquid chromatography. PMID- 2103829 TI - A study of the action of immunosuppressive factors from tumour cells on lymphocytes and macrophages in vitro and on the graft-versus-host reaction in mice. AB - The effect of immunosuppressive factors from P815, B16, and EL-4 mouse tumour cells on the permeability of the lymphocyte membrane to RNAase (the 'membrane toxic effect'), on the generation of tumour necrosis factor (TNF) by mouse peritoneal macrophages, and on the survival rate of mice undergoing a graft versus-host reaction was investigated. The immunosuppressive factors were found to have a membrane-toxic effect on mouse lymphocytes. Moreover, in the presence of pancreatic RNAase there was a dose-dependent increase in the inhibitory effect of the immunosuppressive factors on concanavalin-A-induced spleen cell proliferation. The immunosuppressive factors reduced the production of muramyl dipeptide-induced TNF by mouse peritoneal macrophages. When immunosuppressive factors from P815 cells were administered to F1 hybrid mice (CBA x C57B1/6), there was a marked decrease in the intensity of the graft-versus-host reaction induced by injection of C57B1/6 parent mouse spleen cells to the F1 hybrids, and the life span of these mice was increased. It is suggested that the membrane toxic effect may be one mechanism by which cells in the immune system are inhibited by immunosuppressive factors from tumour cells. PMID- 2103830 TI - Polymer-metal complexes of protein antigens--new highly effective immunogens. AB - The mechanism of interaction of the copolymers N-vinylpyrrolidone-acrylic acid and N-vinylpyrrolidone-maleic anhydride with bovine serum albumin, influenza virus total surface antigen (haemagglutinin and neuraminidase), and the BCG protein fraction in the presence of divalent copper ions was investigated. Novel water-soluble triple polymer-metal complexes of the above protein antigens were formed. These complexes showed high immunogenicity and conferred high levels of immunological protection. Study of the replication of pathogenic influenza A virus in animal lungs showed that, in mice immunised with the triple complex containing surface glycoprotein influenza virus A antigens, reproduction of the homologous virus was sharply inhibited, and immunisation of B mice, exhibiting pronounced T-cell deficiency, with complexes containing the BCG protein fraction ensured development of a high level of protection with respect to BCG infection. PMID- 2103831 TI - Properties of intrathymic T-lymphocyte precursors--targets of thymocyte growth factor (THGF). AB - Primary and long-term thymocyte cultures were used to analyze intrathymic T lymphocyte precursors (TLP), the targets of thymocyte growth factor (THGF). It is shown that THGF has an effect on TLP not only as a growth factor, but also, and first of all, as an activation factor, triggering autocrine TLP proliferation. This is realized through secondary products, such as IL-2, IL-3, and THGF of endogenous origin, secreted by the THGF target cells. The intrathymic TLP that respond to THGF are resistant to high doses of irradiation (up to 50 Gy), and because they are in a quiescent state they can remain viable for long periods under unfavourable culture conditions. These TLP are apparently the self-renewing stem cells of the thymus, and are probably involved in the regeneration of this organ under extreme and adverse conditions, providing TLP of other types with growth factors. Data are presented which suggest that proliferation of the THGF target cells is realized in an unusual way, combining formation of daughter cells within the mother cell with ordinary mitosis. PMID- 2103832 TI - Inhibition of monoamine oxidase by esters and peptides of aromatic amino acids. AB - Methyl esters of aromatic a-amino acids, peptides with N-terminal tyrosine and C terminal arginine, and amides of peptides with N-terminal aromatic amino acids all inhibit monoamine oxidases A and B from rat liver mitochondria with an IC50 of 0.2-3 mM. PMID- 2103833 TI - Effect of antibodies to granular perforin and calmodulin on the activity of natural killer cytotoxic factor. AB - It was previously established that the cell death induced by natural killer cytotoxic factor (NKCF) is a complex calcium-dependent two-stage process. In the initial stage, during the first 30 min of incubation of NKCF with target cells, pore formation on the surface of the target is observed, together with temporary membrane damage. The second stage cytolytic activity occurs after a 3 h latent period, reaches maximum at 24 h, and leads to cell death. A more detailed analysis of the NKCF-dependent lysis of cells was carried out in a study of the action of antibodies to granular perforin and calmodulin on this process. It was established that pore formation in the membrane after 30 min and cell lysis over the next 24 h are interdependent stages of a single process. The interaction of antibodies to perforin with the perforin-like protein of NKCF led to blockage of pore formation and to subsequent inhibition of target cell lysis. Treatment of NKCF with antibodies to calmodulin gave rise to the appearance of pore-forming activity in the first 30 min of incubation with target cells and to the subsequent acceleration of cell lysis over the next 24 h. PMID- 2103834 TI - The effect of arginine-vasotocin on the production of steroid hormones by mouse, cow, and chicken ovarian tissues in vitro. AB - The effect of arginine-vasotocin (50 ng ml-1) on the in vitro production of progesterone, testosterone, and oestradiol by isolated cow and chicken ovarian follicles and mouse ovaries was studied. This peptide (1) enhanced the release of progesterone into the medium by the ovarian tissues of all three species of animal; (2) inhibited the production of oestradiol by mouse and cow ovaries; (3) had no significant effect on testosterone secretion in any of the species studied. The results obtained indicate that arginine-vasotocin directly influences steroid production in mammalian and avian gonads. PMID- 2103835 TI - Amino acid complementarity: testing of hypotheses. AB - To determine whether hypotheses about the complementarity of amino acids based on the genetic code reflect the amino acid contact preferences found in natural proteins, the average contact probabilities for hypothetical complementary amino acid pairs were compared with those for all possible remaining pairs of the corresponding subset. A statistically significant preference was found for contact between amino acids with codons which had the same central nucleotide. Conversely, the contact probabilities for amino acids with complementary codons either did not exceed, or exceeded only insignificantly, the value for the corresponding remainder subset. The data obtained do not support the hypothesis for the complementarity of peptides coded by complementary RNA strands. PMID- 2103836 TI - Carcinogenesis in rats by nitrosodialkylureas containing oxygenated alkyl groups. AB - A number of asymmetric nitrosodialkylureas containing ethyl, hydroxyethyl, 2 hydroxypropyl, 2-oxopropyl or chloroethyl on one or the other side of the nitroso function were given to male and female F344 rats in drinking water. The two compounds containing a 2-oxopropyl group, ethylnitrosooxopropylurea and oxopropylnitrosochloroethylurea were also given by gavage at the same weekly doses as in drinking water. The effect was greater following gavage treatment, both in tumor incidence and in mortality rate. The most potent carcinogen was ethylnitrosooxopropylurea which induced a large variety of tumors, including lung, nervous system, colon, intestine, thyroid, skin and uterus tumors, mammary adenocarcinomas and mesotheliomas. A similar pattern of tumors was induced by ethylnitrosohydroxyethylurea and hydroxyethylnitrosoethylurea. Hydroxyethylnitrosochloroethylurea, hydroxypropylnitrosochloroethylurea and oxopropylnitrosochloroethylurea gave rise to tumors in fewer organs. Chloroethylnitrosohydroxypropylurea was very toxic to the kidneys and induced a few lung tumors. Skin tumors were commonly induced by the nitrosodialkylureas in drinking water, but not when given by gavage. PMID- 2103837 TI - Invasive blood pressure measurements in restrained but non-anaesthetized mice. AB - We have developed a procedure for directly measuring mean arterial blood pressure in fully awake, non-anaesthetized mice. The technique involves surgical implantation of a small tube into the carotid artery. This tube is then passed under the skin, out through the nape of the neck, and secured in a position which exposes it to the surface. Mice are allowed to recover overnight and are then transferred to jigs which lightly restrain them while allowing access to the tube still inserted in the carotid. By attaching the tube to a pressure transducer, repeated or continuous measurement of blood pressure is possible. PMID- 2103838 TI - Immunological effects of tumor vaccines: II. T cell responses directed against cellular antigens in the viral oncolysates. AB - Peripheral blood mononuclear cells (PBMC) from patients with epithelial adenocarcinoma of the ovary treated in vivo with tumor vaccines administered as viral oncolysates (VO) exhibited significant proliferative responses in vitro to VO as well as to cellular oncolysates (CO). These responses were dependent on the concentration of VO or CO. VO consisted of lysates from the same ovarian tumor cell lines 2774 and CaOV3 infected in vitro with the avirulent strain of influenza virus A/PR8/34. CO were lysates from the same ovarian tumor cell lines without virus. Depletion experiments with the OKT3 monoclonal antibody plus complement demonstrated that these proliferative responses are T cell specific and under the control of the HLA-D region. Furthermore, these T cell responses are directed against both tumor tumor cellular components and tumor HLA class I molecules. These responses can be detected as early as two weeks after the first intraperitoneal injection of VO and reach a maximum 12-16 weeks after the first application of VO for treatment. PBMC from ovarian patients that received in vivo VO exhibited insignificant proliferative responses to CO prepared from human fibroblasts or tumor cell lines of hematopoietic origin. In contrast, they exhibited significant proliferative responses to CO prepared from a human cervix tumor cell line. These results demonstrate systemic T cell activation by antigens in the tumor vaccines in patients with epithelial ovarian carcinoma after in vivo intraperitoneal administration of VO. PMID- 2103839 TI - Hormones and mammary tumour disease in the female dog: an update. AB - In both toxicity studies and epidemiologic studies in veterinary medicine it has been demonstrated that ovarian steroids as well as many synthetic derivatives may enhance mammary tumour formation in the dog. Abnormalities in pituitary function, in particular of growth hormone secretion, have been assumed to take part in this process. In this paper the pathogenetic role that endogenous and exogenous hormones may have in canine mammary tumourigenesis is reviewed. The available evidence suggests that steroid hormones act at an early stage in the development of tumours by stimulating the proliferation of normal epithelium. This leads to an increase in the number of susceptible cells. A growth-stimulatory action may further be exerted upon cells that have undergone partial malignant transformation, but possibly to a lesser extent upon fully malignant cells at a late stage of tumour development. In advanced mammary cancers steroid receptor presence is infrequent, which may indicate a more autonomous pattern of growth. No support has been found for the earlier assumption that growth hormone overproduction is an important factor in canine mammary tumourgenesis. The role of prolactin and thyroid hormones in this process remains uncertain. PMID- 2103840 TI - Cellular aspects of the pathogenesis of radiation--induced thymic lymphomas in C57 BL mice (review). AB - Radiation-induced thymic lymphomas in C57Bl/Ka mice are interesting models for studying the successive steps of carcinogenesis. Irradiation initiates "preleukemic" cells, which are promoted to become neoplastic. Studies in mice in which lymphoma development is inhibited by a bone marrow transplantation after irradiation suggest that radiation--induced alterations to the T cell lineage, and particularly to thymic microenvironment, are critical for the promotion of preleukemic cells. It is proposed that the lack of physiological differentiation signals within the thymus, as a result of irradiation, allows these cells to escape the normal controls of thymocyte production and pushes them towards neoplastic transformation. A disturbance in the production of cytokines may be involved, since exogenous cytokines, such as Interferon gamma or Tumor Necrosis Factor a, can inhibit radiation-induced lymphomagenesis, reproducing the effects of bone marrow transplantation. The model is thus suitable for studying the mechanisms of carcinogenesis and designing biological manipulation devoted to cancer prevention in individuals who have been exposed to oncogenic agents. PMID- 2103842 TI - Response to doxorubicin and cyclophosphamide of a human pleural mesothelioma clinically and as a xenograft in nude rats. AB - The effect of doxorubicin (DOX) and cyclophosphamide (CYC) on human pleural mesothelioma AKG was evaluated clinically and compared to the response of the same tumour as a xenograft in athymic rats. The response of the xenograft to each of the drugs was assessed as reduction of the area under the tumour--volume curve (1-AUC), as reduction of the relative tumour volume (1-RTV) and as specific growth delay (SGD) induced by the drug. Treatment of the xenograft with DOX (7mg/kg i.p.) as a single drug at the maximum tolerated dose (MTD) in athymic rats resulted in 1-AUC, 1-RTV and SGD of 0.54, 0.44 and 0.77, respectively. Likewise, treatment with CYC (100 mg/kg i.p.) at MTD resulted in 1-AUC, 1-RTV and SGD of 0.72, 0.45 and 0.73, respectively. Drugs were denoted as active if 1-AUC greater than 0.85, 1-RTV greater than 0.64 or SGD greater than 2. Consequently, both drugs were classified as inactive against the xenograft, corresponding to the progression of the patient's tumour during treatment with a combination of DOX and CYC at MTD. PMID- 2103841 TI - Uterus-derived growth substances: possible implications for human uterus physiology and pathophysiology (review). The Group for Gynecological Investigation. AB - The presence of mitogens and inhibitors in myometrial, endometrial and leiomyoma extracts was documented. Growth substances of human uterus extracts were sensitive to tryptic digestion and were acid stable. Mitogens and inhibitors were retained and could be eluted from cartridges of octadecylsilyl-silica by 80% acetonitrile. Reverse-phase high performance liquid chromatography (r-HPLC) could separate mitogens from inhibitors. In addition, r-HPLC profiles revealed eluates of myometrial and leiomyoma extracts containing mitogens with preferential activity for either osteoblasts or myoblast-like cells, respectively. The presence of mitogens and inhibitors in human uterine extracts suggests a possible involvement of these growth substances in the regulation of various physiological and pathophysiological processes of human uterus. PMID- 2103843 TI - Evaluation of a new nitrosoureido water-soluble sugar, ecomustine or CY 233 (NSC 609224), on human xenografts. AB - Because of its wide spectrum of activity against murine models regardless of the route of administration, CY 233 (NSC 609624) was investigated in human tumours xenografted in nude mice, namely one amelanotic melanoma, MeXF 274, and three colon adenocarcinomas, i.e. CXF 233, CXF 243 and CXF 609. CY 233 was highly active against the MeXF 274 melanoma and produced a complete response on day 14 at 20 mg/kg given i.v. on days 0 and 7. After three intermittent i.v. injections of 10 mg/kg, it produced a partial response of long duration against the colon adenocarcinoma CXF 243. The interesting fact that resistant lines responded to CY 233 warrants further investigation of other schedules of treatment and of the sensitivity profile of CY 233 in a wider panel of tumour xenografts. PMID- 2103844 TI - Gastric stump carcinomas in rats--a reliable gastric cancer model? AB - There is an increased risk of developing gastric carcinoma after surgery for peptic ulcer disease in humans. It is often claimed that alkaline reflux from the intestine to the stomach is a carcinogenic factor of importance in this development. In a rat model which mimics the procedures done in humans, different investigators have found an astonishingly high frequency of malignant changes. We report our findings in 19 rats operated with gastroenterostomy without resection, of which 9 developed dysplastic changes. In seven (37%) these could be classified as carcinomas or high grade dysplasia. This frequency of malignant changes is lower than that found by others. The histological classification, however, reveals substantial difficulties which are discussed. Mucin histochemistry revealed an intestinal type of cancer. PMID- 2103845 TI - The fatty acids available to wild herbivores from indigenous plants is dependent on both plant species and season. AB - Considerable evidence shows dietary nutrient variation of human foods, but little data is available for wild animals. Plants are known to be low in total lipid, thus limiting essential fatty acid availability to herbivores. The fatty acid profiles of a range of indigenous Southern African plants were examined. Significant differences were detected, both between species, and within species according to season. No differences related to geographical location were detectable. PMID- 2103846 TI - Angiotensin-converting enzyme inhibitor-induced renal failure: causes, consequences, and diagnostic uses. AB - Angiotensin-converting enzyme inhibitor-induced renal failure is now a well recognized phenomenon that appears to occur almost exclusively in patients with a preexisting reduction in renal perfusion pressure, especially those with renovascular disease. In the latter group of patients, renal failure probably results from some combination of reduced poststenotic renal perfusion pressure and a unique disturbance in the autoregulation of glomerular filtration rate. Although traditionally regarded as functional and reversible, recent animal studies suggest that angiotensin-converting enzyme inhibitor-induced reductions of glomerular filtration rate may lead to progressive renal atrophy, an observation that raises concerns about the long-term safety of these agents in patients with renovascular disease. On the other hand, the deleterious consequences of angiotensin-converting enzyme inhibition in renovascular disease have been exploited as aids in the diagnosis of this disorder. Whether the adjunctive use of angiotensin-converting enzyme inhibitors will prove to be useful in screening large populations of hypertensive patients for renovascular hypertension remains to be determined. However, such adjunctive tests appear to be useful in judging the functional significance of angiographically documented renal artery stenosis. PMID- 2103847 TI - Endothelial derived relaxing factor controls renal hemodynamics in the normal rat kidney. AB - These studies were conducted in the conscious, chronically catheterized rat to determine whether the endothelial derived relaxing factor (EDRF) controls renal function in the normal state. Administration of the EDRF synthesis inhibitors N monomethyl-L-arginine (NMA; 100 mg/kg body weight) or N-nitro-L-arginine methylester (NAME; 10 mg/kg body wt) led to a large, sustained rise in blood pressure, a large rise in renal vascular resistance, a fall in renal plasma flow, a relatively slight reduction in glomerular filtration rate, and a consequent rise in filtration fraction. In addition, a marked natriuresis occurred because of a reduction in the fractional reabsorption of sodium. In separate studies, a continuous infusion of excess L-arginine (300 mg/kg body wt bolus followed by 50 mg/kg body wt per min) attenuated the NMA- or NAME-induced rise in blood pressure and reversed the renal hemodynamic effects such that a significant rise in renal plasma flow was seen. L-Arginine alone produced a selective renal vasodilation and large increases in sodium excretion. These observations support earlier suggestions that tonic release of EDRF controls the basal blood pressure and also show that renal function in the normal unstressed rat is markedly influenced by EDRF. These studies suggest that, in addition to controlling renal plasma flow, EDRF may have other, complex actions at the glomerulus. The natriuresis seen after acute inhibition of EDRF with NMA or NAME was probably the result of a pressure natriuretic response to the abrupt rise in blood pressure and also, perhaps, reflects removal of an EDRF influence to directly enhance sodium reabsorption somewhere in the nephron. PMID- 2103848 TI - Prostaglandin F2 alpha inhibits the ammoniagenic response to acute acidosis in LLC-PK1 cells. AB - A kidney epithelial cell line, LLC-PK1, which does not synthesize prostaglandins, provides an ideal in vitro model system to investigate the effect of prostaglandins in the regulation of renal ammoniagenesis. Previous studies from our laboratory have demonstrated significant increases in glutamine-dependent ammonia and alanine production by rocked cultures of LLC-PK1 cells subjected to either acute metabolic or respiratory acidosis. In the study presented here, experiments were conducted to investigate the role of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) in the response of ammonia metabolism to acute metabolic acidosis by LLC-PK1 cells. A low dose of PGF2 alpha (0.1 ng/mL) dramatically inhibited the stimulatory effect of a low pH (pH 6.8) on ammonia production. In contrast, the inhibition of cytosolically generated alanine was less dramatic and averaged only 20% of the effect on ammonia production. Furthermore, PGF2 alpha increased cellular alpha-ketoglutarate concentration, suggesting an increase in intramitochondrial pH. Thus, the cellular mechanism of PGF2 alpha action appears to involve either interference with the cytosolic pH signal or its translation to the intramitochondrial compartment. The inhibitory response of PGF2 alpha on pH-stimulated ammoniagenesis was progressively lost at higher concentrations. Both low-dose (0.1 ng/mL) and high-dose (10 ng/mL) PGF2 alpha had no significant effect on the basal rates of ammonia and alanine production at pH 7.4. PGE2, on the other hand, did not exhibit any significant response on ammonia or alanine production at either pH 6.8 or 7.4 when given in a wide range of doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103849 TI - Tetraethylammonium transport by OK cells. AB - Mechanisms exist in renal proximal tubules for the mediated transepithelial secretion or reabsorption of endogenous and exogenous organic cations. In the studies presented here, the uptake of the organic cation tetraethylammonium (TEA) into confluent monolayers of opossum kidney cells was evaluated to determine if these cells might serve as an in vitro model of this transport pathway. 3H-TEA entered opossum kidney cells in a time-dependent manner. Uptake at early time points was saturable with an apparent Km of 59.1 +/- 11.2 microM and a Vmax of 1,292 +/- 210 fmol/micrograms of DNA. TEA uptake was inhibited in a dose dependent manner by several other organic cations including amiloride, cimetidine, verapamil, procainamide, quinidine and N1-methylnicotinamide. With 1 mM concentrations of these compounds, uptake was virtually eliminated. However, another organic cation, N'-methylnicotinamide caused only minimal inhibition. TEA uptake was significantly reduced by sodium azide, suggesting dependence on oxidative phosphorylation. An alkaline medium pH enhanced TEA uptake, but, at the same pH, uptake was similar in the presence or absence of bicarbonate. When cellular pH was altered by ammonium chloride addition or removal, TEA uptake was not affected. Thus, organic cation/proton exchange, as has been demonstrated previously in apical membrane vesicles prepared from proximal tubules, is evidently not responsible for TEA uptake. Similarly, uptake does not appear to result from organic cation/organic cation exchange. These results indicate that the plasma membrane of opossum kidney cells contains a transport system(s) for the mediated uptake of organic cations and that these cells may be a useful mode for further study of renal epithelial transport of these solutes. PMID- 2103850 TI - Inorganic mercury transport in the proximal tubule of the rabbit. AB - Inorganic mercury transport was studied in the S1, S2, and S3 segments of the isolated perfused proximal tubule of the rabbit. The concentration of mercury in the perfusate was 18.4 microM. At this concentration all three segments of the proximal tubule underwent degenerative changes that proceeded to cellular necrosis at the end of the tubule which was attached to the perfusion pipet. This pathological process progressed along the tubule for approximately 200 microns. The remainder of the tubule, to the collection pipette, remained intact and free of any pathological changes. In examining the transport of mercury under these condition, it was found that, on average, the S1, S2, and S3 segments all removed inorganic mercury from the luminal fluid at approximately 140 fmol min-1 mm-1. The transport of mercury, as measured by the appearance of 203Hg in the bathing solution, was 80% lower than the removal of 203Hg from the luminal fluid. The mercury appearing in the bath could be accounted for by passive leakage through the necrotic portion of the tubule in the S1 and S2 segments, but not in the S3 segment. Leakage could account for only 16.2% of the transepithelial movement of inorganic mercury in the S3 segment. Inorganic mercury taken up by the tubule (92%) was primarily associated with the structural proteins of the tubular epithelial cells, while very little (8%) was found in the tubular extract. The toxicity of inorganic mercury was determined by titration. Perfusion with 1 microM inorganic mercury produced necrosis. The pathological features appeared to be the same as those resulting with 18.5 microM inorganic mercury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103851 TI - Cyclosporin A stimulates transcription and procollagen secretion in tubulointerstitial fibroblasts and proximal tubular cells. AB - The brief study described in this report was undertaken to determine whether cyclosporin A had any direct effect on the expression of tubulointerstitial procollagens in cultured renal cells. Our findings indicate that murine tubulointerstitial fibroblasts secreted significantly more procollagen type I after the addition of cyclosporin A, whereas syngeneic proximal tubular cells expressed significantly more types I and IV procollagen after cyclosporin stimulation. These increases in procollagen gene product correlated concordantly with changes in the levels of cytoplasmic mRNA with procollagen-specific cDNA probes. Transfection of these fibroblasts and proximal tubular cells with chimeric gene constructs containing enhancer/promoter elements for alpha2(I) and alpha 1(IV) procollagen linked to a chloramphenicol acetyltransferase reporter gene indicates that the stimulatory effect of cyclosporin on procollagen expression depends, at least to some extent, on an increase in transcriptional activity. PMID- 2103852 TI - Sequential and simultaneous "in series" hemodialysis and hemoperfusion in the management of theophylline intoxication. AB - Hemodialysis and hemoperfusion have been evaluated, and both are effective in removing theophylline. We report two consecutive cases of theophylline intoxication in which the sequential treatment of charcoal hemoperfusion and hemodialysis is contrasted to the simultaneous "in series" treatment of hemodialysis and charcoal hemoperfusion. Analysis of the two methodologies shows that the combined in series technique offers several advantages, including increased extraction efficiency, decreased time of hemoperfusion cartridge saturation, and rapid correction of electrolyte and acid-base abnormalities, and that it is well tolerated clinically. Simultaneous hemodialysis and charcoal hemoperfusion should be considered in cases of extreme theophylline intoxication. PMID- 2103853 TI - The envelope of HIV-1 as a key component to infectivity. PMID- 2103854 TI - The histopathology of tuberculosis in the acquired immunodeficiency syndrome: a study of nine cases. PMID- 2103855 TI - The clinicopathologic spectrum of bacillary (epithelioid) angiomatosis. PMID- 2103856 TI - Disseminated histoplasmosis in the acquired immunodeficiency syndrome. PMID- 2103857 TI - The lymph node in AIDS: a light microscopic and ultrastructural study. PMID- 2103859 TI - Some facets of cryptosporidiosis. PMID- 2103858 TI - Disseminated strongyloidiasis and other selected unusual infections in patients with the acquired immunodeficiency syndrome. PMID- 2103860 TI - Acalculous cholecystitis in the acquired immunodeficiency syndrome. PMID- 2103861 TI - Neoplastic diseases in children with acquired immunodeficiency syndrome. PMID- 2103862 TI - Diagnostic yields of surgical specimens from patients with AIDS or at risk for AIDS. PMID- 2103863 TI - The immunohistology of lymph nodes in HIV infection: a review. AB - Most available evidence indicates that lymph node immunohistologic alterations in HIV-infected patients represent a dynamic process characterized by an initial florid follicular hyperplasia that ultimately progresses to a burned-out, lymphocyte depletion end-point. During this process, HIV-infected cells appear to traffic through the lymph node, and the germinal center serves as a reservoir relatively rich in HIV antigens and intact virus. The localization of HIV within the germinal center may provide one stimulus for the florid follicular hyperplasia typical of early HIV-related lymphadenopathy and may play a role in follicle lysis, a process whereby the accessory cell FDC network of follicles undergoes disruption, which may in turn be responsible for the eventual disappearance of B-cell follicles in late-stage disease. Lymph node CD4+ T cells are selectively depleted with an initial preferential loss of the CD4+ subset concerned with B-cell differentiation. The expression of the CD4 antigen by various other cell types including monocytes, macrophages, histiocytic dendritic cells, and FDC provides one explanation as to why these cells are subject to HIV infection. Except perhaps in end-stage disease, alterations among various lymph node cell subsets do not correlate well with those in the peripheral blood. The latter is therefore regarded as a more sensitive parameter of progressive immunologic changes in HIV infection. PMID- 2103864 TI - Lymph nodes in HIV-positive drug abusers with persistent generalized lymphadenopathy: histology, immunohistochemistry, and pathogenetic correlations. AB - Persistent generalized lymphadenopathy (PGL) represents an important aspect of the natural history of AIDS. It is a reactive lymphadenitis appearing in HIV positive drug abusers and homosexual men, involving lymph nodes mostly located in the neck and in axillary regions. This present review chapter describes the most salient histological and immunohistochemical features of lymph nodes of intravenous drug abusers affected by PGL. Microscopic changes are homogeneous and essentially comparable allowing to subgroup nodes according to their histologic pattern: those with hyperplastic and those with regressive changes. Hyperplastic changes include hyperplasia of germinal centers without or with fragmentation and vascularization, and increased postcapillary venules in the paracortex. Regressive changes are characterized by follicular involution and by follicular depletion with or without fibrosis. Immunohistologic phenotyping shows a peculiar infiltration of CD3/CD8+ lymphocytes in germinal centers and a progressive lysis of follicular dendritic reticulum cells. The presence of HIV antigens can be demonstrated in germinal centers with a reticular pattern paralleling that of follicular dendritic reticulum cells, in endothelial cells of paracortical venules, and in sinus macrophages. Furthermore, HIV genome is sometimes detectable by in situ hybridization in a few endothelial and mononuclear cells of the paracortex. Epstein Barr virus (EBV) antigens are occasionally observed in a few lymph node cells, while EBV genome seems to be absent during the PGL phase of the HIV infection. In conclusion, during PGL, immunohistologic features correlate well with the extent of the histologic changes. PMID- 2103865 TI - Bone marrow findings in HIV infection: a pathological study. AB - The histopathologic changes of bone marrow during infection with the human immunodeficiency virus type 1 (HIV-1) are described. Bone marrow biopsies from 73 patients at different stages of HIV-1 infection were studied. Indications for biopsy included peripheral blood abnormalities, suspicion of lymphoma, or search for specific pathogens. Common histopathological features, suggestive of HIV-1 infection but nonpathognomonic were hypercellularity (67%), myelodysplasia (86.1%), plasmacytosis (98.6%), lymphocytic infiltration (31.1%) and histiocytic infiltration with or without granulomata (13.7%). Increases in reticulin fibers (54.7%), and stainable iron deposits, vascular congestion and serous atrophy of fat were frequent features. Opportunistic infections and neoplastic complications were detected in 7 cases: pathogens were demonstrated in 4 cases (Mycobacterium avium intracellulare (MAI), Cryptococcus neoformans, Toxoplasma gondii and Leishmania) and lymphoma in 3 cases (1 Burkitt lymphoma and 2 Hodgkin's disease). Bone marrow hypoplasia is usually a terminal event in AIDS and may be iatrogenic. PMID- 2103866 TI - Benign lymphoepithelial lesion and lymphoepithelial cyst of the parotid gland in HIV infection. PMID- 2103867 TI - Pulmonary complications in patients with the acquired immunodeficiency syndrome: diagnostic methods. PMID- 2103868 TI - Improving the quality of hospital services in The Netherlands. The role of CBO- The National Organization for Quality Assurance in The Netherlands. AB - In The Netherlands, quality assurance activities in hospitals began in 1976 with a formal declaration of the National Specialists Organization that quality assurance is a task of the medical profession. It was also recognized that physicians in hospitals were as yet unable to execute the various tasks that come with formal quality assurance. Hence the creation of a support organization that would assist clinicians in taking up and fulfilling their commitment to quality assurance. The creation of CBO took place in 1979; its role has been expanded to encompass such functions as technical assistance, education and training, research and development, acting as a clearing-house, and providing a forum. CBO has recently obtained an additional function; acting as a role model for similar structures in other countries in Europe and on other continents. A network of support organizations has been formed through which the development of quality assurance in health care is furthered. PMID- 2103869 TI - Better policy to promote the evaluative clinical sciences. AB - 1. The failure to evaluate the outcomes of surgical practice, diagnostic tests and the uses made of hospitals contrasts sharply with the careful evaluations now mandated for drugs. This double standard for truth in medicine compromises the rationality of medical decisions with significant, deleterious consequences for patients and the health care economy. The uncertainty physicians face about the scientifically correct way to practice medicine results in large variations in the costs and quality of care, even among sophisticated medical communities. The examples of variations between Boston and New Haven are discussed in this paper. 2. Uncertainty about the scientifically and ethically correct way to practice medicine is not inevitable. The double standard for truth can be removed by extending science policy to include the systematic assessment of different treatment theories physicians use in treating common illnesses. Experience (discussed in this presentation) shows that such assessments result in a substantial improvement in the scientific basis of medicine that is of value to patients, physicians and all who are concerned about the quality of care. 3. Information that will improve the scientific basis of medicine for patients, physicians and policy makers can be obtained within a few years--as few as two or three--and without regulation. Conditions should be targeted for assessment that affect the most patients and are of importance to those concerned about cost and quality. It is imperative that the assessments be conducted according to high scientific standards and become an integral part of a nation's medical research program. 4. My paper elaborates on the need for the program, strategies for assessments and the principles that should guide science policy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103870 TI - Quality assurance for drug prescribing. AB - This article reports the results of a critical analysis of English-language studies describing programs designed to improve physician prescribing behavior in primary care settings. Only 64% of studies met minimum research design standards, and are the basis for the results reported. The overall findings of the review confirm the conclusions of a previous evaluation of hospital-based studies. (1) The simple dissemination of printed educational materials had no detectable effect on prescribing practice when used alone in well-controlled studies. However, such educational materials do lay a necessary foundation for more personalized educational efforts. (2) Merely distributing computerized listings of patient-specific medication profiles, without specific recommendations for change, is ineffective in reducing overall drug costs or use of inappropriate drugs. Their lack of effect may be due to the large quantity and clinical irrelevance of such data. (3) Continuous computerized reminder systems have been shown to prevent omission of essential care, although such systems are effective only as long as reminders continue. This strategy has not been evaluated for its potential to reduce excessive or inappropriate drug prescribing. (4) Repeated feedback to physicians with specific suggestions for alternative agents has been shown to increase use of generic drugs in academic group practice settings. No adequate studies have tested whether this approach might reduce other types of misprescribing. Also in academic primary care settings, small group tutorials have been shown to improve use of antibiotics and hypertension treatment control. (5) A substantial literature in the U.S. and Canada supports the conclusion that brief, face-to-face educational outreach visits, conducted by either specially trained clinical pharmacists or physician "counsellors" and "opinion leaders", are effective in reducing prescribing of inefficient or contraindicated drugs in pediatric and adult primary care settings. These face-to-face approaches emphasize a tactful, supportive and facilitative role; in some cases, emphasis is put on helping physicians overcome barriers to appropriate prescribing (e.g. patient demand or addiction to minor tranquilizers). Most effective programs also utilize professionally credible sponsors and high-quality educational materials. In addition to improving quality, some programs have been found to produce savings in drug use which exceed the operational costs of the program. PMID- 2103871 TI - Quality assurance and effectiveness in health care: an overview. AB - Increasing interest in quality assurance and effectiveness in health care has been generated by three major things: about 20% of care is consistently demonstrated to be inappropriate, variations in practice cannot be explained by patient or facility factors, and decreased utilization as a result of changing economic and regulatory incentives seems to lead to both inappropriate care and appropriate care reduction. This interest has led to at least three changes in the approach to quality assurance. First, a move from measuring practitioner competence to measuring population health outcomes. Second, less use of implicit judgements and greater attention to explicit standards (e.g. practice guidelines) and explicit processes to establish the standards. Third, less organizational isolation of quality assurance and greater efforts to integrate it into everyday activities and across levels of health care delivery. PMID- 2103872 TI - Systems of standards for community health services in Australia. AB - This paper describes how the Australian Community Health Association (ACHA) has facilitated the development of quality assurance systems for community health services in Australia. The systems are based on the standards and review process produced by the Community Health Accreditation and Standards Project, known by its acronym "CHASP'. The paper outlines principles and organisation of community health services in Australia and some background to their development. It then considers what kind of standards and quality assurance methods are appropriate for community health services. The CHASP model of standards and its associated review process is explained. The paper discusses how the ACHA has worked with various states in Australia to establish systems of standards based on the CHASP work. It concludes by looking at some constraints and opportunities in developing CHASP, and some future directions. PMID- 2103873 TI - Informed inquiry into practice variations: the Maine Medical Assessment Foundation. AB - This paper reports on the development of a successful physician organized and driven medical assessment program, the Maine Medical Assessment Foundation. Responding to the issues and challenges presented by practice pattern variation in the state of Maine, eight physician specialty study groups have been developed in the state over the past ten years. Working in a confidential, educational, non regulatory format, study groups have had remarkable success in providing feedback of epidemiologic data on area variations to practitioners. This process has succeeded in modifying practice patterns, resulting in marked improvements in quality of care and decreases in apparently excessive utilization of health care resources. Simultaneously, physicians have become supporters of the process of small area analysis and they have joined in community based outcomes research projects. This successful program can be a model for other areas. PMID- 2103874 TI - Outcomes and quality assurance: facilitating the use of administrative data. AB - To evaluate quality of care, a two-step approach seems appropriate. First, highly structured explicit criteria, based on patient outcomes such as mortality, readmissions, or unusually long lengths of hospital stay, might help identify adverse events using routinely-collected discharge data. Then, process criteria might be used for subsequent medical record reviews to determine whether a quality problem exists. Large administrative data bases suggest the possibility of developing an epidemiology of quality of care; understanding how quality problems are distributed across the hospitals in a province seems feasible. Population-wide data are essential for comprehensive follow-up and for effective studies of medical practices. Hospital-based follow-up can miss important events; we found the relative percentage of short-term readmissions to hospitals other than the hospital of surgery startling. However, hospital-based data can sometimes be used in place of the more costly and harder-to-generate population data for quality monitoring. For example, in examining correlations among various outcome indicators following five common surgical procedures, we found the ranking of hospitals according to inhospital mortality to be highly correlated with their ranking according to 30-day post-surgical mortality. PMID- 2103875 TI - Concepts of quality of care: national survey of five self-regulating health professions in Canada. AB - Discussions of quality assurance mechanisms for health professions are increasing in Canada. In their roles of protecting the public from incompetent or unsafe health care, and enhancing the quality of care provided by practitioners, provincial licensing organizations are taking an interest in quality assurance programmes. The paper reports the results from a national survey of five self regulating health professions (dentistry, medicine, nursing, optometry and pharmacy) in Canada. The study found two types of activities in place--a complaints programme and a routine audit programme. Both programmes use a similar approach to identifying poor performers within a health profession. The paper discusses the results of the study, the advantages and disadvantages of the approach used, and suggests a second approach to quality assurance which could be used in conjunction with current activities. PMID- 2103876 TI - Quality of alternative medicine--complications and avoidable deaths. AB - Patients with diseases, known to respond well to treatment within the conventional medical system, may be adversely affected if treatment with alternative medicine is given instead. In order to analyse to what extent this may occur in Sweden, a mail survey was carried out. Two hundred and forty-two heads of departments of pediatrics, internal medicine, rheumatology, neurology and oncology were asked to supply case reports where such alternative treatment had resulted in either a delay of diagnosis of a disease, where effective therapy was available, or in substitution of effective conventional therapy with alternative medicine. Eighty-four out of 233 clinics reported 123 cases from the period 1984-1988, most of them from internal medicine. Six patients died following alternative treatment and 27 had to be treated in intensive care units after severe complications of alternative treatment. In most cases health resort managers had withdrawn effective medication or instituted vegetarian diets for patients with severe catabolic conditions, such as collagen diseases, renal insufficiency or inflammatory bowel disease. Twenty-three children had been treated by alternative medicine in violation of the Swedish law against quackery, but legal action had not been taken in any case. The study, which, by design, may only reveal the tip of an iceberg, suggests that apart from the well-known direct complications, associated with alternative treatment, such treatment may further prevent patients from obtaining. PMID- 2103877 TI - Peer review in primary care. AB - In a district of the town of Nijmegen in the Netherlands, 322 family physicians were approached to take part in an intensive peer review programme: 73% agreed to take part. The problems doctors experienced at the start of the programme were: a dislike of being criticized and doubts about such an investment of time. As the programme got going most of the problems shrank in size whilst the problem of changing their practice routines to meet certain guidelines for quality of care imposed by the programme grew. Nevertheless, for the large majority participation was a very valuable experience. By means of a gradual and personal approach towards doctors, systematic procedures for assessment and feedback, variation in topics and methods, and good organization and guidance it is possible to make quality assurance by means of peer review into a valuable aspect of the daily work of many care providers. PMID- 2103878 TI - The regulation of medical devices and quality of medical care. AB - Medical devices are now a pervasive part of modern medical care. They are in many cases associated with quality of care. In some cases, the use of devices has certainly improved quality. In other cases, devices can be associated with many problems. The approach to quality of devices has depended largely on regulation. However, regulation of devices in Europe is rather undeveloped, so in many cases the reliability and safety of a device has not been independently established and one cannot assume that a particular device in fact is reliable or safe. In addition, there are many problems in the interface between the machine and the user or the patient that are largely untouched by device regulation, and perhaps should be more often considered in quality assurance programs. As essential as device regulation is, it is not sufficient to assure quality. Education is particularly important in this area. Quality assurance programs need to be familiar with common problems with medical devices and how to approach them. PMID- 2103879 TI - Medicare mortality rates and hospital quality: are they related? AB - In 1987, the Health Care Financing Administration (HCFA) compiled and released mortality information for 1986 Medicare admissions to 5,971 United States hospitals. Full triennial accreditation surveys were conducted by the Joint Commission on Accreditation of Healthcare Organizations in 1,628 of these institutions in 1986. This report examines the relationship between 1986 Medicare mortality rates and hospital quality, as measured by accreditation survey performance. Hospitals with higher-than-expected and lower-than-expected mortality rates were compared on three measures of accreditation survey performance. These comparisons were made for three mortality groups: overall, stroke, and acute heart disease. No statistically significant (p = 0.05) differences were found in survey performance for any of the mortality groups compared. This lack of association between mortality and hospital quality, as measured by accreditation performance, reinforces concern about the use of mortality rates as measures of quality for public policy or patient decision making purposes. PMID- 2103880 TI - The provision of urethral catheters: an equipment audit. AB - Although medical and nursing audit is attaining a high profile in UK hospitals, the development of objective measures remains a challenge. The availability and storage or urinary catheters was recorded by a point prevalence survey in a District General Hospital. A "long-term" and "short-term" catheter were provided in all areas, but seven further brands of catheter were found. Female length catheters were rarely available. With some limited exceptions there were no written or verbal policies concerning selection of catheters in the wards. Excess numbers of catheters were stored by wards responsible for their own ordering. Damage of catheters during storage was noted. The survey provided a simple, rapid and inexpensive method of audit to rationalise and improve the provision of catheters. The implementation of a policy incorporating the selection, ordering, storage and use of such equipment will both optimise patient care and maximise efficient budgeting. PMID- 2103881 TI - Are in-hospital deaths and long stay markers for errors in surgery? AB - To test the feasibility of using a system for classification of surgical errors and of in-hospital deaths and long hospital stay as markers for errors in surgery we reviewed the hospital records of 273 patients with 285 admissions. During the one year study period there were in all 3767 patients admitted for surgical care. From these we selected the 131 who died in the department during the year, the 100 who had the longest stay (greater than 33 days) and the 91 patients were referred to the departments of internal medicine, infectious diseases or orthopedic surgery. Errors were classified as error of omission or commission, in diagnosis or in therapy. Possible or definitive errors were found in the care of 23% of the patients who died and in 10% of the ones with a long hospital stay. Only 3% of patients referred to other departments experienced errors. It is concluded, that "in-hospital death and "long hospital stay" can be used as markers to identify errors in surgery. PMID- 2103882 TI - Do peer consultations improve quality of care in general practice? AB - The present study relates to three aspects of quality of care in general practice: attention paid to somatic aspects, patient orientation and risk of unnecessary harm. Quality of care had been measured by (a) a written simulation of patient-doctor encounters, which includes five patients and (b) rating procedures. The study has been carried out in two steps. Firstly several aspects of peer consultation have been investigated in a group of 184 doctors (response rate: 83%), who had their vocational training in the department of General Practice of the University of Utrecht. One third of the GPs consulted colleagues frequently and continued to do so for long periods, dealing systematically with a variety of problems, one third did so infrequently or unsystematically, and one third did little or no consulting at all. A relationship was found between the type of practice and consulting behaviour: 20% of those who practice alone never consulted peers, whereas those in group practices and health centres are accustomed to do so regularly. Secondly, 49 doctors were selected from the 184 mentioned above. The 49 did not differ from the remainder in several relevant aspects such as practice setting, subscription to medical journals, etc. Peer consultation seems to have a direct relationship with the quality of attention paid to somatic aspects; GPs who do not consult among peers in any way display a lower quality of attention to somatic aspects in comparison to the others. In this study these GPs are all solo physicians.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2103883 TI - The audit of mental health services. AB - Medical audit has been slow to develop in psychiatry. While mental health services present important questions for audit, there are formidable technical problems such as standardising evaluation of the efficacy and efficiency of treatments and deciding who from the multidisciplinary team should be involved. Despite this the methods of case note review, examination of routine statistics, investigation of sentinel events, monitoring the use of compulsion and regular inspection of facilities all have an important role. PMID- 2103884 TI - Pattern formation in Drosophila. PMID- 2103885 TI - Dorsal ventral polarity and pattern formation in the Drosophila embryo. AB - The establishment of polarity along the dorsal-ventral axis of the Drosophila embryo requires the graded distribution of the dorsal morphogen. Several maternal genes are responsible for the formation of the gradient and their products act in an ordered series of events that begins during oogenesis and involves two different cell types, the oocyte and the follicle cells. The last step in the series results in selective nuclear localization of dorsal proteins, dorsal is thought to regulate the expression of zygotic genes in a concentration dependent way. The zygotic genes determine cell fates in specific regions of the embryo and direct other genes involved in the processes of differentiation. PMID- 2103886 TI - The organization of the antero-posterior axis. AB - The components specifying the spatial coordinates of the Drosophila embryo are deposited in the egg during oogenesis. Three maternal pathways control the pattern of the embryo along its antero-posterior axis. Genetic and molecular analysis has identified the key-genes in each of these pathways: (1) the bicoid gene encodes an anterior signal in the embryo that directs head and thorax formation via transcriptional activation of anteriorly expressed zygotic genes. (2) A posterior signal, the nanos gene product, antagonizes an inhibitor of abdominal development, hunchback, by translational regulation. (3) A terminal signal controls development at both poles of the embryo. It is probably induced by the somatic follicle cells and transmitted to the embryo via a membrane bound receptor encoded by the gene torso. Other maternal genes function in the localization of these signals or in signal transduction. PMID- 2103887 TI - The blastoderm prepattern. AB - During the first 3h of development the Drosophila blastoderm is subdivided into segments along the anterio-posterior axis. This is achieved by three classes of genes: gap, pair-rule and segment polarity. The gap and pair-rule genes interpret cues provided by the localized maternal determinants. These transient intermediate patterns then establish the persistent segment polarity gene expression which defines segments throughout development. In so doing they transform maternal gradients which vary gradually over a distance of 40 or so cells into a precise pattern where individual cells are distinguished from their immediate neighbors. PMID- 2103888 TI - Molecular and cellular interactions responsible for intrasegmental patterning during Drosophila embryogenesis. AB - The elaboration of pattern within insect segments is a well-studied example of cellular patterning during development. This process requires that each cell develop appropriately for its position. Experimental embryology suggests that intercellular communication plays a key role in imparting positional information to cells. Drosophila genetics has identified numerous genes whose activity is required for patterning within segments, and whose molecular genetic analyses suggest they constitute and control cell communication circuits. Particular genes are expressed or required by cells that will follow distinct developmental pathways, and some appear to confer or interpret intercellular signals. Other patterning genes are ubiquitously required and may provide the machinery through which the signals are transmitted. PMID- 2103889 TI - Early neurogenesis. AB - After the symmetry of the early embryo is disrupted by morphogenetic movements, one of the first differentiation events is the appearance of discrete neural precursors, the neuroblasts, which segregate from a defined region of ectoderm. Within this region, presumptive epidermal precursors are intermingled with the neuroblasts. Sorting between these fates appears to depend upon cell-cell interactions and requires the function of two sets of genes; one whose mutant phenotype results in an excessive central nervous system (CNS) and the other a subnormal CNS. Molecular cloning of these genes reveals striking homologies which can place the products into two camps. The first are recognizable cell surface components (and potential signal transducers), and the second DNA binding proteins, plausibly transcription factors. PMID- 2103890 TI - Genes involved in the development of the peripheral nervous system of Drosophila. AB - The development of the peripheral nervous system (PNS) requires the activity of a number of genes. The neurogenic and the proneural genes are necessary in the earliest phase; their mutations lead to hyperplasia and partial or total elimination of the PNS respectively. Some of these mutations also affect other developmental processes. Other mutations affect later events: cut transforms one type of sensory organ into another; numb alters the fate of the components of a single sensory organ. We will describe the effects of the best studied mutations on PNS development and discuss the possible role of the wild type genes. PMID- 2103891 TI - The molecular basis of pattern formation in the developing compound eye of Drosophila. AB - Throughout metazoan development cells select pathways of specialization that lead to the differentiation of specific cell types. Differential gene activation converts initially homogeneous populations of cells into spatial arrangements of diverse cell types. As discussed in other articles in this issue, the signals specifying divergent pathways can be encoded in a cell's lineage, its environment, or a combination of both. This article reviews recent analyses of the developing Drosophila compound eye which have focussed upon the mechanisms by which cells assess environmental information in order to determine their fate. More specifically, it examines the molecular mechanisms used by cells to communicate signals which instruct the developmental pathways of other cells. PMID- 2103892 TI - Pattern formation in imaginal discs. AB - Imaginal discs are sacs of folded epithelium arising during embryogenesis. They proliferate during the larval instars, and at metamorphosis secrete the adult cuticle, therefore being responsible for the characteristic surface patterning of this insect. Each disc has intrinsic growth controls and their cell lineage shows constraints known as compartments. Spatial patterns emerge through interaction between adjacent cells. Molecular genetic analysis of mutants with changed pattern has implicated transcription factors, secreted, membrane-bound and growth factor related proteins in the position-signalling mechanism. Their accessibility to contemporary cell biological techniques makes imaginal discs a model system for investigating patterning in animal tissues. PMID- 2103893 TI - ATP-dependent proteases in prokaryotic and eukaryotic cells. AB - The energy-requirement for intracellular proteolysis is due largely to the involvement of large multimeric proteases whose function requires ATP hydrolysis. The best-studied such enzyme is protease La from E coli. This tetrameric protease is inhibited in vivo until the binding of an unfolded protein allostericically activates its peptidase and ATPase functions. This mechanism and tight transcriptional regulation prevent non-specific or excessive proteolysis. E. coli contains another ATP-hydrolyzing protease, Ti (Clp), which contains distinct ATPase and proteolytic subunits. Enzymes homologous to La and Ti exist in mitochondria and chloroplasts. In eukaryotic cells, a major neutral proteolytic activity is the 650 kDa proteasome. This multicatalytic structure can function as an ATP-dependent protease or as part of the ATP-dependent complex that degrades ubiquitinated proteins. In mammalian muscle this 1300 kDa complex is formed by an ATP-dependent association of the proteasome with another ATP-dependent protease complex, multipain. Much remains to be learned about the physiological roles and mechanisms of these novel proteases. PMID- 2103894 TI - PEST sequences are signals for rapid intracellular proteolysis. AB - Many features of a protein can enhance its degradation within cells. Unlike thermal lability or oxidizability which increase the likelihood of damage, PEST sequences are built-in signals for destruction. These stretches of polypeptide chain rich in proline (P), glutamate (E), serine (S) and threonine (T) are invariably found in rapidly degraded enzymes, transcriptional factors and components of receptor signalling pathways. They are, by contrast, rarely present among long-lived cellular proteins. In this brief essay, I review the properties of PEST sequences, recent experimental support for the idea that they are indeed proteolytic signals, and possible pathways for catabolism of PEST proteins. PMID- 2103895 TI - Non-selective autophagy. AB - Autophagy is the major process by which cells degrade their own cytoplasm. Autophagy begins with the sequestration of a portion of the cytoplasm by a membraneous organelle called a phagophore. The resulting vacuole (autophagosome) can fuse with an endocytic vacuole to form am amphisome, which subsequently fuses with a lysosome to have its mixed autophagic/endocytic content degraded by lysosomal enzymes. Autophagy is a non-selective bulk process as indicated by the fact that hepatocytic cytosol enzymes with widely different half-lives are sequestered at the same rate. Regulation of autophagy is exerted at the sequestration step by amino acids, purines, ATP-depleting metabolites, cyclic nucleotides, phosphorylation, and hormones like insulin, glucagon and alpha adrenergic agonists. PMID- 2103896 TI - A selective pathway for degradation of cytosolic proteins by lysosomes. AB - A lysosomal pathway of proteolysis is selective for cellular proteins containing peptide sequences biochemically related to Lys-Phe-Glu-Arg-Gln (KFERQ). This pathway is activated in confluent cultured cells that are deprived of serum growth factors and in certain tissues of fasted animals. We have reconstituted this lysosomal degradation pathway in vitro. Transport into lysosomes requires a KFERQ-like sequence in the substrate protein and uptake and/or degradation is stimulated by ATP. A member of the heat shock 70 kDa protein family, the 73 kDa constitutive heat shock protein, binds to KFERQ-like peptide regions within proteins and, in some as yet unidentified manner, facilitates transfer of the proteins into lysosomes. Several possible mechanisms of selective protein transport into lysosomes are discussed. PMID- 2103897 TI - Biochemical analysis of normal and osteoarthritic human cartilage. AB - Non-collagenous proteins from the articular cartilage of normal subjects and patients with degenerative joint disease were extracted sequentially. Proteoglycans and the other glycoproteins were more extractable from the osteoarthritic cartilage at lower ionic strength than those from the normal cartilage. A 50-kD protein which seems specific to osteoarthritic cartilage was identified. Three different populations of proteoglycans were purified from normal and only two from osteoarthritic cartilage. Moreover, greater amounts of albumin and fibronectin were found in the pathological cartilage. No differences were observed between link proteins from normal and osteoarthritic cartilage, nor in their molecular weight or the amounts extracted. PMID- 2103898 TI - Composition of amino acid infusions and effect of cholecystokinin on insulin release in dogs. AB - In the present study we have examined if the different composition of intravenously administered amino acid solutions is of importance for the effect of cholecystokinin (CCK) on pancreatic insulin and glucagon release in dogs. In 6 conscious dogs CCK-9 was infused intravenously at stepwise increasing doses of 5, 10 and 20 pmol/kg.h during an intravenous background infusion of Aminosteril or Aminoplasmal. Aminosteril contains more insulinogenic amino acids while Aminoplasmal contains more glucagonogenic amino acids. CCK elicited a significant stimulation of insulin levels by 10 microU/ml (p less than 0.01) in the presence of i.v. Aminosteril compared to that elicited by i.v. amino acids alone. Glucagon and glucose levels remained unchanged. During i.v. Aminoplasmal CCK-9 had no effect. Since in dogs the physiological plasma amino acid pattern following the ingestion of protein-rich meals is unknown the possibility cannot be excluded that in dogs CCK acts as a mediator of the intestinal signal which augments insulin release during ingestion of protein-rich meals. PMID- 2103899 TI - Quantitation of cumulative release of lactate dehydrogenase isoenzyme-1 in plasma of patients with acute myocardial infarction using a commercially available test. AB - In 27 patients with acute myocardial infarction (AMI) we calculated cumulative release of alpha-hydroxybutyrate dehydrogenase (alpha HBDH) per liter plasma which is a routine procedure in our coronary care unit, and compared these values with calculated cumulative release of lactate dehydrogenase isoenzyme-1 (LDH-1) per liter plasma using a LDH-1 test that has become commercially available recently. Theoretically, myocardial (iso)enzyme release is more accurately determined with LDH-1 than with alpha HBDH, due to the higher cardiac specificity of LDH-1 compared to alpha HBDH. The only disadvantage of LDH-1 is its abundance in erythrocytes necessitating a correction by measurement of free hemoglobin (Hb) concentration in plasma. After division of cumulatively released activities (Q72) of alpha HBDH and LDH-1 by the activities per gram of normal myocardium (135 and 81 U/g, respectively), the values of Q72(alpha HBDH)/135 and Q72(LDH-1)/81 were compared per patient. Elevated alpha HBDH levels in the presence of normal creatine kinase levels in plasma samples taken on admission, as well as hemolysis gave rise to overestimation of cumulative release of alpha HBDH as compared to LDH-1, but hepatic congestion occurring secondary to AMI (48-72 h after onset of infarction) did not disturb the equality of Q72 (alpha HBDH)/135 and Q72(LDH 1)/81 values. In 16 patients showing none of the mentioned conditions, the relation between Q72(alpha HBDH)/135 and Q72(LDH-1)/81 coincided with the line of identity (r = 0.97). We conclude that the use of an easy and rapid plasma LDH-1 assay improves the assessment of enzymatic infarct size, provided free Hb levels are measured to correct LDH-1 activities for a contribution by erythrocytes. PMID- 2103900 TI - Comparative analysis of certain metals and tumor markers in bronchopulmonary cancer and colorectal cancers. Metals and tumor markers in the neoplastic process. AB - Carcinogenic metal levels in serum and tissue samples were measured in patients with bronchopulmonary or colorectal cancer. The cadmium and nickel tissue levels in the patients with lung cancer were significantly higher than in the controls. A statistical correlation was found between chromium and cadmium, as well as between cadmium and nickel in patients with colorectal cancer. In addition, prior to the operation, the tumor markers alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (Ca 19-9), polypeptide histidio antigen (TPA) and ferritin were analyzed. Their average concentrations were correlated with the existing concentrations of the metals. This was done for both types of cancer. Tumor marker detection showed an increase of CEA and TPA in patients with colorectal cancer. A statistical correlation was observed between AFP and zinc tumor tissue. PMID- 2103901 TI - Recovery from insulin-induced hypoglycemia after saccharose or glucose administration. AB - This study compared the effects of saccharose and glucose on the recovery from insulin hypoglycemia. 17 normal volunteers (12 men, 5 women, 25-40 years old) received the same dose (0.1 IU i.v.) of semisynthetic rapid-acting human insulin on two different days after an overnight fast. Blood glucose and C peptide were measured in venous blood samples before as well as at regular time intervals after insulin administration. 30 min after the injection, 20 g saccharose or 20 g glucose p.o. (diluted in water) were given. The mean glucose values were at most time intervals higher after glucose than after saccharose administration. In addition, glucose ingestion resulted in an earlier and steeper blood glucose rise (mean recovery rates during the first 5 min 3.10 and 1.38 mg/dl/min for glucose and saccharose, respectively). The C peptide values decreased progressively and did not achieve baseline levels even at 120 min in spite of blood sugar normalization. It is concluded that glucose acts faster than saccharose in insulin-induced hypoglycemia. Exogenous insulin results in a prolonged depression of C peptide which lasts longer than the hypoglycemic effect. PMID- 2103902 TI - Comparative study on the validity of diaphragm and cantilever strain gauge in dental research. PMID- 2103903 TI - Corrosion behaviour of dispersalloy amalgam and non-precious alloys in artificial saliva of different pH. AB - Corrosion behaviour of dispersalloy amalgam and non-precious alloys in artificial saliva of different pH was studied using potential and capacitance measurements. In slightly acidic media, the amount of potential shift for all alloys studied is, small as compared to more acid media, pH = 1.85. On the other hand, in alkaline saliva, especially of higher pH, 12.01, the potential shift for dispersalloy amalgam, is higher than that of non-precious alloys. Further, Wiron S alloy showed the most resistive alloy in such media. The results of capacitance measurements are in general accord with those implied by the potential. The corrosion potential of the non-precious alloys-amalgam combinations reflect the activity of Wiron S-amalgam combination and inertness of the other combination. All amalgam samples exhibit a gradual loss of the surface luster with blackish discoloration and pitting after a long exposure period to the medium. PMID- 2103904 TI - Influence of reinforcement on the creep behaviour of polymeric denture base. PMID- 2103905 TI - Clinical evaluation of polyvinyl siloxane for complete and partial denture impressions. PMID- 2103906 TI - The influence of finishing and polishing on reflectivity of some esthetic materials. PMID- 2103907 TI - Anterior veneers for the adolescent patient: 2. Porcelain veneers and conclusions. AB - Composite and porcelain veneers offer a conservative method of masking discolouration of the teeth of younger patients. Composite veneers are the less destructive of tooth tissue, but also the less durable. This two-part article reviews the use of veneers in treating the adolescent patient. Part 1 described the clinical procedure for veneering with composites. Part 2 now gives a guide to porcelain veneer technique, and then draws some overall conclusions. PMID- 2103908 TI - Orthodontic techniques for uprighting the mesio-angularly impacted lower third molar. AB - An impacted lower third molar can sometimes be uprighted orthodontically to provide a functional tooth. Many such cases can be managed by the interested GDP, although more complex mechanics are probably best left to the specialist. This article reviews the indications for treatment, and describes appropriate techniques. PMID- 2103909 TI - Survival analysis in practice. AB - Survival analysis is a versatile statistical tool that has been used in dentistry to evaluate such diverse subjects as the longevity of restorations, the natural history of caries and caries risk. It is hoped that this article will help readers to understand better such studies and make their own interpretation of the results, and even to carry out similar evaluations among their own patients. PMID- 2103910 TI - Fracture of the mandible in a child. AB - If unusual injuries to the teeth are present, these should serve as a warning to practitioners that further investigations may be necessary. In the case reported here an undisplaced fracture of the jaw in a young child was only revealed by radiographic investigation. PMID- 2103911 TI - Highly esterified granulated apple pectin and lipid metabolism. PMID- 2103912 TI - Cerebral haemodynamics and anxiety in depressive patients. PMID- 2103913 TI - Psychometric investigation of the neurotic condition of women with myoma uteri. PMID- 2103914 TI - A ten-year follow-up of postoperative results of the treatment of urinary incontinence. PMID- 2103915 TI - Problems of genetic counseling in the presence of supernumerary marker chromosomes (case reports and a review of publications). PMID- 2103916 TI - Analysis of a group of indices of forced expiration in various types of ventilatory disturbances. PMID- 2103917 TI - An experimental study of the effect of low level helium-neon laser irradiation on the reparative processes of the cornea after perforative injury. PMID- 2103918 TI - Pulse therapy of patients suffering from collagenoses. PMID- 2103919 TI - Early and late complications in patients with acute myocardial infarction- comparative evaluation after fibrinolytic treatment. PMID- 2103920 TI - Development of epidemiological services in India. PMID- 2103921 TI - Presidential address: 34th annual conference of Indian Public Health Association. PMID- 2103922 TI - Dr. B. C. Dasgupta Memorial Oration. Control of rheumatic fever and rheumatic heart disease. PMID- 2103923 TI - Dr. K. N. Rao Memorial Oration. Comparative competence measurement evolving standardised rates constant (ESR constant) for PHC area or any other area simple scientific screening system-sine statistics. PMID- 2103924 TI - Dr. P. C. Sen Memorial Oration. A study of utilisation of family planning services through MCH package care in rural areas of West Bengal. PMID- 2103925 TI - A study of accidental poisoning (in children) in a rural medical college hospital of West Bengal. AB - 134 cases of accidental poisoning in children have been reported, children belonging to the age group of 1-3 years are the main victims. Kerosene has been noted as the single most important cause of poisoning. Mortality was fortunately low amounting to 5.2% of all cases. PMID- 2103926 TI - Studies on the comparative efficacy of mebendazole, flubendazole and niclosamide against human tapeworm infections. AB - The efficacy of Mebendazole and Niclosamide was studied in two groups of 24 and 38 cases, respectively of patients suffering from taeniasis. Mebendazole with dose schedule of 200 and 300 mg twice daily for 3 consecutive days showed a cure rate of 71.42% and 92.30%, whereas Niclosamide at the dose rate of 200mg per patient was 94.76% effective. Flubendazole showed a cure rate of 66.66% only. Mebendazole and Niclosamide possess high taeniacidal activity, ability to reduce the clinical symptoms of taeniasis without any side effects. Niclosamide with high activity and excellent tolerance, is a drug of choice for the treatment of taeniasis in single dose treatment while for hymenolepsiasis it needs extended course. PMID- 2103928 TI - [Difficult problems on basic structure of terminal apparatus of intestinal nerve plexus]. PMID- 2103927 TI - Female sterilization-acceptor characteristics. PMID- 2103929 TI - [Morphology and pleomorphism of smooth muscles]. PMID- 2103930 TI - [Excitatory contraction of smooth muscles: special reference to intracellular calcium]. PMID- 2103931 TI - [Calmodulin dependent regulation of smooth muscle contraction]. PMID- 2103932 TI - [Comparative physiopathologic study on congenital Hirschsprung's disease and acquired esophageal achalasia]. PMID- 2103933 TI - Effect of 2-methyl-5-hydroxytryptamine on motility of the isolated guinea-pig colon. PMID- 2103934 TI - Changes in sensitivity to agonists in vascular smooth muscle of the autografted artery. PMID- 2103935 TI - Differences in tension oscillation in aortae of hypertensive and normotensive rats. PMID- 2103936 TI - Enzymatic lysis of sulfated glycosaminoglycans reduces the electrophoretic mobility of vascular endothelial cells. AB - The main purpose of this work was to identify the macromolecules carrying the surface charge of endothelial cells. This was done by measuring changes in cell electrophoretic mobility caused by enzymatic removal of glycocalyx components. Endothelial cells were removed from the bovine pulmonary artery using nonenzymatic procedures, plated, and identified by immunocytochemical methods and electron microscopy. Cultured cells were suspended in saline and placed in the lumen of a capillary in a Rank Brothers electrophoresis instrument. Voltage was applied between the ends of the capillary, and the velocity acquired by the cells was measured with a microscope. Preincubating the cells in protein-free saline for 1 h reduced the mobility by 25%. This reflects the loss of proteoheparan sulfate from the cell surface. Cell mobility was totally suppressed by exposing the entire cell surface to chondroitin sulfate lyase, but it was only slightly diminished when the enzyme was applied only to the cell side facing the culture medium. A partial decrease in mobility was obtained after enzymatic removal of either heparin, heparan sulfate, or collagen. The results indicate that sulfated glycosaminoglycans are the main carriers of the surface change in vascular endothelial cells. The asymmetrical effect of chondroitinase on the two sides of the cell indicates a distribution polarization for glycosaminoglycans in endothelial cells. PMID- 2103938 TI - Mutation Research. Annual cumulative index. Vol. 228-245 (1990). PMID- 2103937 TI - Kinetics of myo-inositol transport in corneal endothelial cells: diverse effects of sugars and implications in corneal deutergensence [corrected]. AB - Kinetics of myo-inositol (MI) uptake into primary cultures of bovine corneal endothelial cells (CEC) were studied. Confluent corneal endothelial cells accumulated 3H-MI in a time dependent and saturable process. At a narrow range of external concentrations of 3H-MI (4-50 microM), the Na(+)-dependent MI uptake followed saturation kinetics. The apparent Km value was 20 microM with a maximum velocity (Vmax) of 16 pmol/20 min/micrograms DNA. At low external 3H-MI concentrations the uptake was dependent on Na ions, but at higher levels the Na(+)-independent fraction of MI uptake significantly increased. The uptake was sensitive to removal of Ca ions and to the presence of inhibitors such as n-ethyl maleimide, phlorizin, ouabain, and amiloride (an inhibitor of Na+/H+ exchanger). The sensitivity of MI uptake toward inhibitors and ionic changes in the bathing media was reduced as external concentrations of 3H-MI increased. Citrate at 0.5 mM increased the uptake, suggesting involvement of mitochondrial oxidative metabolism in the MI uptake. Percent release of radioactivity by 2 min, after an initial 40-min incubation with 20 microM 3H-MI, was 6.6% +/- 0.8 or 35% +/- 4 when release media contained BSS alone or BSS containing 5 mM nonradioactive MI, respectively. Efflux of radioactivity from the cells also was enhanced when release media contained 40 mM glucose. Glucose and galactose as well as nonmetabolizable glucose analogues, such as 3O-methyl glucose or alpha-methyl glucose, at high concentrations (40 mM), acutely (in the incubation media) or chronically (in the growth media) inhibited MI uptake into CEC, and the extent of inhibition was inversely proportional to the external levels of 3H-MI. However, glucose at lower levels (less than or equal to 10 mM) slightly increased MI uptake. These studies indicated that the uptake of MI into corneal endothelial cells was an Na(+)-dependent active process at a narrow range of external radioactive MI concentrations. Higher levels of MI were taken up by the cells via a passive diffusion mechanism, independent of carrier protein(s). Glucose influenced the uptake of MI in a complex manner. The increased MI efflux by glucose or by MI was perhaps due to the limited capacity of CEC for accumulation or compartmentalization of this or other solutes/osmolytes, a phenomenon that may be related to the role of CEC in maintenance of corneal deutergence. High glucose induced inhibition of Na(+)-dependent MI uptake may be in part due to glucose regulation of Na+ fluxes and cell volume.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2103940 TI - ACLI president's message. PMID- 2103939 TI - Cellular differentiation in the process of generation of the eukaryotic cell. AB - Primitive atmosphere of the earth did not contain oxygen gas (O2) when the proto cells were generated successfully as the result of chemical evolution and then evolved. Therefore, they first had acquired anaerobic energy metabolism, fermentation. The cellular metabolisms have often been formed by reorganizing to combine or recombinate between pre-existing metabolisms and newly born bioreactions. Photosynthetic metabolism in eukaryotic chloroplast consists of an electron-transfer photosystem and a fermentative reductive pentose phosphate cycle. On the other hand, O2-respiration of eukaryotic mitochondrion is made of Embden-Meyerhof (EM) pathway and tricarboxylic acid cycle, which originate from a connection of fermentative metabolisms, and an electron-transfer respiratory chain, which has been derived from the photosystem. These metabolisms already are completed in some evolved prokaryotes, for example the cyanobacterium Chlorogloea fritschii and aerobic photosynthetic bacteria Rhodospirillum rubrum and Erythrobacter sp. Therefore, it can be reasonably presumed that the eukaryotic chloroplast and mitochondrion have once been formed as the result of metabolic (and genetic) differentiations in most evolved cyanobacterium. Symbiotic theory has explained the origin of eukaryotic cell as that in which the mitochondrion and chloroplast have been derived from endosymbionts of aerobic bacterium and cyanobacterium, respectively, and has mentioned as one of the most potent supportive evidences that amino acid sequences of the photosynthetic and O2 respiratory enzymes show similarities to corresponding prokaryotic enzymes. However, as will be shown in this discussion, many examples have shown currently that prokaryotic sequences of informative molecules are conserved well not only in those of the mitochondrial and chloroplast molecules but also in the nuclear molecules. In fact, the similarities in sequence of informative molecules are preserved well among the organisms not only in phylogenetically close relationships but also under highly selective pressure, that is under a physiological constraint for the species in their habitats. Therefore, the similarities in amino acid sequences of proteins between the prokaryotes and the organelles are not necessarily direct evidence for their phylogenetical closeness: it gives still less evidence for a symbiotic relationship between the prokaryotes and the organelles. The metabolic compartmentalization of the membranes is an important tendency in cellular evolution to guarantee high specificity and rate of the metabolisms. It is suggested from the data that the intracellular membranes are not static but undergo dynamic turnover. Furthermore, these facts strongly support the Membrane Evolution Theory which was proposed by one of the authors in 1975. PMID- 2103941 TI - Inflammatory bowel disease. PMID- 2103942 TI - Screening for gastrointestinal disease--a critical analysis. PMID- 2103943 TI - Apolipoprotein fractions and risk of cardiovascular disease. PMID- 2103944 TI - Implications of preclinical genetic diagnosis. PMID- 2103945 TI - AIDS in the 1990s: challenges and directions. What are we in for? An epidemiologist's perspective. PMID- 2103946 TI - HIV: the U.S. military experience. AB - We have tracked the prevalence, the incidence, and the acceleration of HIV infection within our populations. We have measured the efficacy of our control efforts in objective ways that are biological end points. And, more importantly, we are treating people who are infected in a compassionate and humane way. PMID- 2103947 TI - HIV testing panel: the difficult issues. PMID- 2103948 TI - Genetic testing committee report. PMID- 2103949 TI - Public affairs report. PMID- 2103950 TI - ACLI legislative--regulatory report. PMID- 2103951 TI - Medical Information Bureau. PMID- 2103952 TI - The impact of new cardiovascular interventions on prognosis of patients with coronary artery diseases. PMID- 2103953 TI - Silent myocardial ischemia--does its presence provide additional prognostic information? PMID- 2103954 TI - Life and health insurance medical research fund report. PMID- 2103955 TI - Risk factor and complications in the patient with diabetes mellitus. PMID- 2103956 TI - Sleep apnea. PMID- 2103957 TI - Asthma--prognostic implications in the 1990s re: morbidity-mortality evaluation. PMID- 2103958 TI - [Allergy to cow's milk]. AB - Cow's milk allergy is a disease of infancy and usually appears in the first few months of life. The evaluation of infants for possible cow's milk allergy is one of the more common problems encountered by pediatricians. Unfortunately, both over and under diagnosis is frequently seen. In this review the pathophysiology, the clinical manifestations, the diagnosis and management of infants with cow's milk allergy as well as the prevention of the condition in predisposed infants are discussed. PMID- 2103959 TI - Temporal organization of cerebrovascular accidents: a retrospective, preliminary study about stroke in Ferrara, Italy. AB - An epidemiologic retrospective study was conducted from January 1984 to December 1988 on subjects admitted into the Institute of Semeiotica Medica of the University of Ferrara (as a general medicine, unselective department) and presenting a stroke. Year, month and hour of onset of symptoms in 141 patients (all resident in Ferrara, mean age 74.3 +/- 8.3 years) were carefully recorded. The definition of precise clock hour was reached only in 108 cases. The data were then analyzed by means of Halberg's single cosinor. Time series analysis showed a seasonal pattern of disease onset, characterized by a circannual rhythm with acrophase in late winter - early spring (-83.9 degrees). A significant circadian rhythm was found too, with acrophase at afternoon (-242.8 degrees). PMID- 2103960 TI - Mucin histochemistry in Barrett's esophagus. AB - Specimens from twelve patients with Barrett's esophagus and four additional cases of esophageal carcinoma who had Barrett's epithelium were histologically and by mucin histochemistry examined. Specialized epithelium was observed in 10/12 non cancerous patients. In 9 of these either gastric-fundic or junctional epithelium were seen. All patients with carcinoma had evidence of specialized epithelium. Sulphated mucins were preponderant in biopsies from 7 of the 9 patients with dysplasia either alone or associated with carcinoma. In all 5 specimens with specialized epithelium but without dysplasia or carcinoma, sialomucins were predominant. PMID- 2103961 TI - Prognostic value of serum thymidine kinase and beta 2 microglobulin in subjects affected by multiple myeloma. AB - The authors, using a radio-enzymatic and a radio-immunological method, investigated the serum levels of Thymidine Kinase (TK) and Beta 2 Microglobulin (Beta 2M) in 24 subjects affected by Multiple Myeloma (MM) and in 10 controls. The data obtained confirm the good prognostical significance already reported for TK and Beta 2M in subjects with MM. First of all, the results indicate higher levels of TK compared to the controls (9.31 U/l vs 2.9 U/l - p less than 0.005). Similarly, also the levels of Beta 2M indicate a significant increase compared to the healthy subjects. Both TK and Beta 2M levels increased with the progression of the stage of the disease (6.69 mg/ml vs 1.67 mg/ml - p less than 0.005). After therapy there was a significant decrease of TK and Beta 2M levels in responders. Finally, TK demonstrated to be able to detect during the follow-up a possible relapse of the disease. PMID- 2103962 TI - [Acute aortic dissection: diagnostic possiblities of mono- and two-dimensional echocardiography]. AB - A case of an acute aortic dissection (AAD) has been reported in a 61-year-old woman, in whom, by the mono and two-dimensional echocardiography (M and 2D E) the authors have detected: 1) The disconnection between the intima and adventitia. 2) A flap of the intima in the aortic cavity. The authors emphasize the usefulness of the M and 2D E because it permits: 1) An early diagnosis of the AAD. 2) A reduction of the lapse between the angiographic examination and the surgical therapy. 3) A better prognosis. PMID- 2103963 TI - [Infective endocarditis of the tricuspid valve: echocardiographic diagnosis and a therapeutic approach]. AB - The authors report a case of Infective Endocarditis (IE) to emphasize the most characteristic echocardiographic features that permit to detect the tricuspid valve involvement in IE, the management of the medica and/or surgical therapy of this disease and the limitations of this noninvasive technique. PMID- 2103965 TI - [Current pediatrics: cow's milk allergy]. PMID- 2103964 TI - Analysis of folate and vitamin B12 in beta thalassemia minor. AB - To evaluate whether anemia of heterozygote beta thalassemic subjects depends on folate or vitamin B12 deficiency, the serum values of these two vitamins were assessed in 176 adult subjects: 81 healthy heterozygote beta thalassemic subjects, 76 healthy normal controls and 15 subjects with microcytic iron deficient anaemia and no thalassemic trait. Mean serum folate and vitamin B12 levels in heterozygote beta thalassemic subjects were not statistically different when compared to control groups. No statistically significant correlation was found between mean serum levels of the two vitamins and hematocrit in beta thalassemic carriers and in normal subjects. PMID- 2103966 TI - [Ciprofloxacin in the treatment of bronchopulmonary infections]. AB - Ciprofloxacin was given orally in dosages of 250 mg or 500 mg every 12 hours for a period of 8-13 days. Most patients had chronic bronchitis in the acute stage. The favourable results achieved and the complete absence of side effects show that ciprofloxacin is a useful drug in the treatment of respiratory tract infections. PMID- 2103967 TI - [Beta-cyclodextrin-piroxicam in the treatment of the active phase of osteoarthritic pathology]. AB - The anti-inflammatory and analgesic activity of the beta-cyclodextrin-piroxicam (beta CDP) complex was assessed in a randomized single-blind controlled parallel study vs nabumetone (NAB). Forty patients, 18 men and 22 women aged 18 to 65 and suffering from chronic osteoarthritis, were treated. Both drugs were orally administered, once a day in the morning, for 4 consecutive weeks. PI and SPID, evaluated for 24 hours following the first drug administration, showed a quicker onset of the analgesic action of beta CDP, with statistically significant differences between treatments (p less than 0.05). In the medium-term treatment, beta CDP proved to be more effective on joint swelling, spontaneous pain, pain on passive movement and functional limitation. Both treatments were well tolerated but a higher gastro-intestinal side-effect incidence was recorded in NAB group. PMID- 2103968 TI - [Osteoarthritic disease: therapy with oxicam derivatives]. AB - Two groups, each composed of 20 elderly patients suffering from osteoarthritis characterised by intense pain, were treated for 4 weeks with the oral formulation of two modern oxicam derivatives (tenoxicam capsules and beta-cyclodextrin piroxicam tablets respectively). The analysis of the results showed that both drugs have an excellent antalgic effect. After the first dose the action of beta cyclodextrin-piroxican was quicker and more marked, with statistically significant differences between treatments for the first 4 hours. At the end of the study period the two drugs proved to be equally effective, with a more pronounced symptomatic effect of beta-cyclodextrin-piroxican. No side effects serious enough to warrant suspension of treatment were observed: the only side effects reported were gastric adverse events (pyrosis, gastralgia) in both groups, having an incidence of 50% (tenoxicam) and 15% (beta-cyclodextrin piroxicam) respectively. PMID- 2103969 TI - [Evaluation of reduction of NSAID consumption after local treatment with a heparin-heparinoid combination in patients with osteoarthritis]. AB - The efficacy of treatment with a heparin-glucuronilglucosaminoglycane association for external use was tested, in a double blind design, on clinical symptomatology and consumption of analgesic drugs (FANS) in patients affected with painful osteoarthritis of the knee. In the course of a 3-week treatment, the following parameters were evaluated: a) concerning the symptoms, intensity of spontaneous pain and of pain induced by both passive mobilization of the joint and walking; b) concerning the analgesic treatment, reduction of FANS consumption (expressed as percentage of basal dose) and of intensity of side effects. In the FANS + heparin-glucoronilglucosaminoglycane-treated group, the following were found with respect to the control group: a) higher reduction of pain intensity, statistically significant as far as pain on walking is concerned and higher increase in passive mobility of the joint; b) notable reduction of FANS consumption and intensity of side effects. The possible therapeutic mechanisms are discussed on the basis of both the characteristics of the employed drugs and the pathophysiology of painful osteoarthritis of the knee. PMID- 2103970 TI - The development of a radioimmunoassay system for testosterone (T) and dihydrotestosterone (DHT). Part 2. The preparation of antisera to T. AB - Testosterone-3-O-carboxymethyl-oxime derivative was synthetized and coupled to bovine serum albumin (BSA). The T-3-CMO-BSA conjugate homogenized with Freund's adjuvant used as immunogen was injected multiple sites in rabbits. The antisera collected were characterized in a radioimmunological system, separation with dextran-charcoal using 125I-Testosterone as tracer. The antibody titres varied from one animal to another. The titre of anti-T serum selected for RIA was 1: 10(4)-1: 2 X 10(4) (initial dilution). All anti-T sera 100 percent crossreacted with 5 alpha-dihydrotestosterone but nonsignificant interference was observed with other C19, C21 and C18 steroids. The affinity constant of the selected anti T serum was in the range 1.4-1.9 X 10(9) litres/mole. The data so far published on the antisera toward testosterone are reviewed. We conclude that the selected anti-T-3-CMO-BSA serum may provide assays for testosterone with potential for clinical applications. PMID- 2103971 TI - The development of a radioimmunoassay system for testosterone (T) and dihydrotestosterone (DHT). Part 3. The preparation of radioiodinated testosterone. AB - A two step-method was applied for the preparation of a tracer adequate for a radioimmunoassay (RIA) system for testosterone. Histamine was radioiodinated by the Chloramine-T method and then coupled to testosterone-3-carboxymethyl-oxime (T 3-CMO) derivative. After purification by TLC, the steroid tracer was stable in ethanol for at least four months. Using an anti-T-3-CMO-BSA serum, a (bridge) homologous RIA system for testosterone was developed. The reagents (antiserum, tracer and standard) were incubated 2 hrs at 37 degrees C and then the free radioactivity was removed by a dextran-charcoal suspension. The testosterone RIA system, with the sensitivity of 30 pg/tube, is suitable for the measurement of the steroid hormone in biological fluids and tissues. PMID- 2103972 TI - Calcitonin reserve and the differentiated response to calcitonin in osteoporosis. AB - The authors followed up the effect of calcium and calcitonin administration on phosphorus-calcium balance and on calcium retention, in correlation with the level of endogenous calcitonin, in 20 patients of perimenopause age (40-50 years), with radiologically confirmed osteoporosis. Calcium retention after loading with calcium gluconate (180 mg in i.v. injections) was determined before and after administration of salmon calcitonin (100 IV in i.m. injections). Two types of responses were noted. In a group of patients calcitonin administration determined a rise of calcium retention at the same time with the improvement of other biochemical parameters as well as a normal calcitonin response. The presence of high levels of circulating calcitonin 24h after loading with exogenous calcitonin demonstrated a slower inactivation rate of the hormone in these patients. The other group showed no positive response to calcitonin. The proposed test is a criterion for the selection of the patients with osteoporosis in view of chronic calcitonin treatment. PMID- 2103973 TI - Stimulation of calcitonin secretion by beta-calcitonin gene related peptide in rats. AB - The presence of calcitonin gene-related peptide (CGRP) in both C-cells and nerve fibres around the thyroid blood vessels and follicles suggests that it may play a dual role, one of which may be in hormone secretion. Beta-CGRP injected intracerebroventricularly (icv) (1.875 nmol) caused a significant increase in the calcitonin CT) content of the C-cells in rat thyroid glands. The calcitonin content of the thyroids was determined by a radioimmunoassay using two antibodies and the results were expressed as ng CT/mg of fetal tissue. A significant rise in CT content of the thyroids occurred (5.5 +/- 0.5 n = 6), compared with the controls (3.5 +/- 0.1 n = 6). It is presumed that this change reflects an increase in the rate of secretion of CT in the thyroid glands of those rats so treated. The peptide might act on the central nervous system to stimulate the catecholamine outflow from the thyroid nerves and thereby increase the secretion rate of CT. PMID- 2103974 TI - Testosterone in sera of workers exposed to acrylonitrile. AB - Testosterone was measured through three consecutive years in sera from young and adult male subjects working in a chemical factory exposed to some complex chemical noxae, the major exposure being acrylonitrile (vinylcyanid). In the first yr, (group A), the blood was collected on May 1975 (no 39), the II-nd yr (group B) on March (no 109) and the III-rd yr (group C) on May (no 149). The exposure time varied in each group between 6 mos and 7-10 yrs. For comparison, blood samples were collected from 145 men of comparable age grouped in nonexposed: blood donors (no 37) (group a), new workers (no 23) (group b) and exposed to other chemical noxae in the same factory: Na cyanid (group c, no 23), cyan derivatives (group d, no 22) and pyrolysis (group no 39). The seasonal testosterone variations being considered, the Student's 't' test applied to the hormonal levels in acrylonitrile groups A, B and C showed non significant differences. However, the comparison of the testosterone concentrations in sera of the groups A, B and C vs the control groups investigated during the same month of the year showed much lower levels of the hormone in the first groups (p less than 0.001). These data are suggesting that the exposure to acrylonitrile either by direct participation to the technological chain or by working in the same noxious environment may influence the testosterone synthesis and/or secretion. PMID- 2103975 TI - [The calcitonin (CT) level in subjects with an increased calcium tolerance]. PMID- 2103976 TI - [The genetic mechanisms of lysosomal enzymopathies]. PMID- 2103977 TI - [The genetics of diabetes mellitus]. PMID- 2103978 TI - [Physical maturation and sport participation. Adolescent female athletes]. PMID- 2103979 TI - [Evaluation of athletic potential. Drugs and athletics. Stress reduction in the practice of sports in children and adolescents]. PMID- 2103980 TI - [Manual of sport ability tests]. PMID- 2103981 TI - [Sport traumatic lesions and their prophylaxis]. PMID- 2103982 TI - [Sport participation of children and adolescents with chronic diseases]. PMID- 2103983 TI - [Psychiatric disorders in children in the 90's: where are we going?]. PMID- 2103984 TI - [Immunopathologic classification of and cytogenetic findings in non-Hodgkin's lymphoma]. PMID- 2103985 TI - [Clinical forms of presentation of non-Hodgkin's lymphoma in childhood]. PMID- 2103986 TI - [Treatment of infantile non-Hodgkin's lymphoma]. PMID- 2103987 TI - [Malignant lymphoma in children. Medium- and long-term course]. PMID- 2103988 TI - [Diagnostic imaging in gastroenterology]. PMID- 2103989 TI - [Study and forecast of the trends in perinatal mortality in Spain in the 90's]. PMID- 2103990 TI - [Digestive hemorrhage]. PMID- 2103991 TI - [Vomiting]. PMID- 2103992 TI - [Acute diarrhea]. PMID- 2103993 TI - [Constipation]. PMID- 2103994 TI - [Progress in the diagnosis of chronic diarrhea]. PMID- 2103995 TI - [children and mass media]. PMID- 2103996 TI - [Television and child health. The role of the pediatrician and of pediatrics]. PMID- 2103997 TI - [The radio and children]. PMID- 2103998 TI - [Children, adolescents, and television]. PMID- 2103999 TI - [Dissemination of information and mass media]. PMID- 2104000 TI - [Vesico-ureteral reflux: epidemiologic clinical and physiopathologic aspects]. PMID- 2104001 TI - [Nephropathy caused by reflux]. PMID- 2104002 TI - [Vesico-ureteral reflux: radiologic aspects]. PMID- 2104003 TI - [Problems in pediatric emergencies in the 90's]. PMID- 2104004 TI - [Vesico-ureteral reflux in childhood: medical treatment]. PMID- 2104005 TI - [Vesico-ureteral reflux and surgery]. PMID- 2104006 TI - [Effects of drug consumption on the newborn]. PMID- 2104007 TI - [The adolescent and drug addict child. Pediatric perspective]. PMID- 2104008 TI - [Psychopathologic aspects of drug abuse in childhood and adolescence]. PMID- 2104009 TI - [Problems related to alcohol in children and adolescents]. PMID- 2104010 TI - [Establishing pediatric educational objectives in the curriculum of medicine]. PMID- 2104011 TI - [Objectives in neonatology]. PMID- 2104012 TI - [Children hospitalization in the 90's]. PMID- 2104014 TI - [Objectives in pediatric cardiology education]. PMID- 2104013 TI - [Objectives in infantile gastroenterology, nutrition, and hepatology education]. PMID- 2104015 TI - [Objectives in infantile nephro-urology]. PMID- 2104016 TI - [Objectives in neuro-pediatrics education]. PMID- 2104017 TI - [Objectives in pediatric surgery education]. PMID- 2104018 TI - [Objectives in pediatric immunology and allergy education]. PMID- 2104019 TI - [Objectives in education regarding calcium-phosphorus metabolism and deficiency rickets]. PMID- 2104020 TI - [Infectious pathology]. PMID- 2104021 TI - [Epilepsy in childhood]. PMID- 2104022 TI - [The problem of neonatal convulsions]. PMID- 2104023 TI - [Infantile spasms]. PMID- 2104024 TI - [Convulsive status]. PMID- 2104025 TI - [Pharmacologic monitoring of antiepileptic medications]. PMID- 2104026 TI - [Prognosis in infantile epilepsy. Discontinuation of drug therapy]. PMID- 2104027 TI - [Congenital syphilis]. PMID- 2104028 TI - [Congenital rubella]. PMID- 2104029 TI - Competencies required for nursing in primary health care. PMID- 2104030 TI - The relationship of the health belief model and health locus of control concepts to immunization compliance. PMID- 2104031 TI - Spotlight: nursing and HIV/AIDS. Focus: ethical issues. PMID- 2104032 TI - Cantilever nasal bone grafting with miniscrew fixation. PMID- 2104033 TI - Changing attitudes and practices in foregoing life-sustaining treatments. AB - Advances in medical technology and practices have been associated with improved patient outcomes. At times, the price of this progress has included great financial costs and human suffering. During the last two decades, there have been significant changes in medical practices in America. In the late 1960s and early 1970s, the removal of a respirator or hydration or nutrition from a patient who was not brain dead was considered a deviation from accepted medical practices. In 1976, the Quinlan case allowed the removal of a ventilator from a patient in a persistent vegetative state. Subsequent court decisions in the 1980s have equated hydration and artificial feeding with other forms of life-sustaining treatments and have allowed their withdrawal in patients who were not terminally ill. Prominent physicians have recently stated that it is not immoral for a physician to assist in the rational suicide of a terminally ill patient. Active euthanasia programs in the United States are likely in the near future. PMID- 2104034 TI - The hippocratic irrelevance variable (HIV) PMID- 2104035 TI - Snail toxins. PMID- 2104036 TI - Differential effects of two very low calorie diets on aerobic and anaerobic performance. AB - To determine the effects on physical performance of two different very low calorie diets (VLCD), 10 moderately obese women (BMI 32.7) were tested before and after an outpatient weight loss of 17 kg. Diet 1 (D1, n = 5) subjects lost 17.2 kg on 450-550 kcal/d from common food regimen adjusted for stature providing protein at 1.5 g/kg IBW and less than 10 g carbohydrate (CHO). Diet 2 (D2, n = 5) subjects lost 18.1 kg on a fixed composition 420 kcal/d formula providing 70 g (1.2 g/kg IBW) protein and 30 g CHO. Aerobic performance (VO2 max) was determined on a cycle ergometer. VO2 max did not change with D1 (2.16 to 2.01 l/min), while it decreased on D2 (2.44 to 2.06 l/min, P less than 0.05). Anaerobic function was assessed as peak quadricep strength on an isokinetic dynamometer, with anaerobic endurance taken as the time and number of repetitions to fatigue (less than 50 percent peak strength). Peak strength did not change on D1 (95.8 to 86.2 ft-lb), but it declined with D2 (102.0 to 89.4 ft-lb, P less than 0.05). Anaerobic time to fatigue did not change with either diet group. In conclusion, it is possible that the higher (and individualized) protein intake of D1 allowed the better preservation of VO2 max, while the higher CHO of D2 did not benefit anaerobic function. Our data suggest that physical performance tests could be used to assess for functional tissue preservation when diets are used for major weight loss. PMID- 2104037 TI - Amiodarone and torsades de pointes. PMID- 2104038 TI - The investigation of serum and salivary, immunoglobulin levels in patients with head and neck region cancer. AB - Tumor immunology has been studied in animal experiments. The studies of Prehn and Main in the year 1957, have been pioneer studies. The early diagnosis of cancer, the prognosis, proflaksia and treatment has been studied in several immunological experiments and is still being studied. In the investigations being made before the Second World War mostly the Conditions after the immunological answer has been studied from the beginning where the antigen enters the body and which organs and tissues the antigen enters, which cells do recognise and how the immunological answers is formed. By solving the secrets of the immunological system, oto-immunological, allergic diseases and cancer would be able to be treated easier it is possible that much more better results will be able to be reached with organ transformation. PMID- 2104039 TI - [Clinical comparison of different types of obturators constructed after maxillary resections]. AB - This investigation was carried on eight patients who had undergone partial maxillary resection for the eradication of tumors. Two types of obturators, one being hollow-bulb and the other buccal flange were constructed for each patient, using different impression techniques. When these were compared clinically, it was concluded that buccal flange obturators which were constructed without closed hollow sections were superior to the hollow-bulb obturators with closed nasal sections extending as far as possible into the anterior and lateral aspects of the defect, in comfort, function, speech and stabilization. PMID- 2104040 TI - [Speech and prostheses for congenital cleft palate patients in adulthood]. AB - The surgical treatment should be preferred for cleft palate patients in childhood. However, a prosthesis is favorable for some adult patients. The construction of prostheses are rather complicated for patients who require pharyngeal speech aid in addition to anterior prosthesis. Sound prosthodontic rules are valid in designing a speech aid prostheses. Often stability and retention increase is required for these prostheses. Furthermore, the velar and the pharyngeal sections should not interfere with the muscular activity of pharynx and/or tongue movements during speech and deglutition. This article describes the prosthodontic habilitation of congenital cleft palate patients by means of pharyngeal speech aid prosthesis. PMID- 2104041 TI - [The application of an overdenture with a modified Dolder bar joint]. AB - In this article, a modified Dolder bar attachment application is presented in two cases. The egg-shaped bars are casted in chromium-cobalt metal alloy and the retention loops are made of clasp wire in "omega" shape. The bar attachment has some advantages like being easy to fabricate and having lower cost. The laboratory made modified Dolder bar attachment we used with overdentures provided additional retention for the dentures, minimized the horizontal and vertical movements of the dentures and also strengthened the abutment teeth by splinting. As a conclusion we have tried to show that this attachment can be an alternative to use with overdentures. PMID- 2104042 TI - [Case of gingival hyperplasia due to mouth breathing]. AB - In this article, a severe gingival hyperplasia case which was seen in maxilla and mandible of a 13 years old male patient who has mouth breathing was presented and some knowledges about this subject were reviewed. It was observed that the patient has nasal obstruction and he was called for nasal operation after he finishes the age of eighteen. His luxe primary teeth were extracted. For the time being to provide esthetic and function, gingivectomy was performed on upper and lower jaw. PMID- 2104043 TI - [Overlay dentures]. AB - Overlay dentures which are accepted as superposition appliances have been presented by three cases in this article. These kind of dentures are dedicated as prosthodontic restorations which are applied to extend maxillary arch horizontally in the cases of maxillary collapse. These restorations also increase the vertical dimension which has been lost and so help to improve the facial contour as well as esthetics of the individual-these dentures classified as removable partial or complete overlay dentures are generally applied in the cases of bilateral or unilateral maxillary collapse which have been caused by trauma or tumor resection. PMID- 2104044 TI - [Retrospective research for intra osseous non-odontogenic cysts]. AB - In this research, 483 cases of intra osseous cyst treated in the Maxillofacial Surgery department of A.U. Dental Faculty has been examined. Out of these cases 15 have been non-odontogenic jaw cysts with and without epithelium. In this group 5 were nasopalatinal, 2 were median mandibular, 2 were median palatinal, 1 was globulomaxillary, 4 were solitary and 1 was a bone cyst. Non odontogenic cases have been elevated according to the differing classifications. PMID- 2104045 TI - [Intramuscular hemangioma of the M. massetericus]. AB - Intramuscular hemangiomas are distinct neoplasms originating within normal skeletal muscle. They represent less than I % of all hemangiomas and occur most frequently in the trunk of extremities, perhaps because of the larger muscle volume in these areas. They occasionally occur in the head and neck area and we present an unusual localisation of intramuscular hemangioma; M. Massetericus. PMID- 2104046 TI - [An alternative moulding technique in porcelain fabrication]. AB - In this article a moulding technique for porcelain work that can be used especially in full-mouth and multiple unit restorations, is presented. Through this technique, condensation of porcelain can be achieved properly and the firing shrinkage can be hold in a minimum level. The occlusal form can be controlled in the mouth by a provisional acrilic bridge. A multiple pieced acrilic mould is prepared from the impression taken on the provisional acrilic bridge and is used for building up the full-mouth restoration. It is concluded that this technique can be an alternative which enables us to achieve accurate occlusal form and well condensed porcelain structure. PMID- 2104047 TI - [Psychosomatic diseases and dentistry (report of two psychoneurotic cases)]. AB - Harmful effects that result from psychic influences on the organic control of tissues are known as psychosomatic disorders. Psychologically, the oral cavity is related directly or symbolically to the major human instincts and passions. In this article, before treating two patients, who have gingival recession and itching, the importance and necessity of their treatment of psychiatric disorders were mentioned and the relationship between psychiatry and dentistry is explained. PMID- 2104048 TI - [Non-precious alloys for ceramo-metal restorations]. AB - Rapidly increasing gold prices hastened the widespread use of non-precious alloys for ceramo-metal restorations. Especially base-metal alloys has been considerably improved and has shown much progress after a long period of study and use. Among these alloys, nickel-chromium and cobalt-chromium alloys are quite popular in our country, like in Europe and in U.S.A. Their physical properties are superior than noble-metal alloys which are used for ceramo-metal restorations. However, some questions arise in the dental literature about their corrosion resistance, biocompatibility and porcelain bonding properties. This article reviews the constituents, physical properties, porcelain bonding, biocompatibility and corrosion resistance of nickel-chromium and cobalt-chromium alloys. PMID- 2104049 TI - [The importance of AIDS in dentistry]. AB - AIDS is a disease that has a high percent of mortality, and its etiology is unknown. Its contamination is by blood and sperms, as a result of this, AIDS forms a dangerous for all people dealing with health and for dentists. In this report; AIDS's importance about dentistry and prevention of disease is told. PMID- 2104050 TI - [Thermal compatibility of metal-porcelain system]. AB - The bonding of metal and porcelain through a firing process is rather a complex phenomenon. Besides the factors that act in bonding, the thermal properties of both materials also affect this mechanism. Different expansion and contraction behaviours of porcelain and metal cause some interface stresses. It is observed that the major objectives of the researches are to measure and determine these stresses and expose the variables affecting them. Porcelain glass transition temperature is one of the variables that the studies have focused on. PMID- 2104051 TI - [Intrapulpal temperature change during the setting reactions of various dental cements]. AB - Mixing of certain types of dental materials may produce pulpal injury due to a series of chemical reactions giving way to an exothermic reaction. Three different dental cements; zinc phosphate, polycarboxilate and glass ionomer cements which may increase the intrapulpal temperature were investigated in the present study. The cements were mixed according to the manufacturers' instructions in one group, the liquid and powder ratios were increased by one portion in the other two groups. The intrapulpal temperature changed between 1.32 4.54 degrees C among the three test groups. The intrapulpal temperature rise was markedly influenced when the amount of powder and liquid ratios were changed. PMID- 2104052 TI - [Investigation of the microbiological variations at the empty root canals after retrograde histoacryl filling that is made with pulpectomy at the same time]. AB - Many researchers defended the thesis of eradicating the apical foramen microleakage for a successful root canal treatment. This study has been designed to defect whether microorganisms will grow or not at the empty root canals as a result of the perfect obstruction of the apical foramen with histoacryl of least microleakage retrogradely. The study has been realized on 24 teeth of 6 adult dogs. Histoacryl was used to obstruct the apical foramens and the experimental animals were anesthetized with general anesthesia. Experimental animals were divided into three groups before the operation. At each group, eight teeth of two experimental animals were studied on. Consequently, a great amount of streptococcus kind, lactobacillus and staphylococcus were isolated at the cultures taken from the root canals of 15 days cases. At 30 day cases, peptostreptococus, lacto bacillus and staphylococcus were isolated while at 60 day cases streptococcus pneumonia, and lactobacillus were isolated and evaluated as meaningless. PMID- 2104053 TI - [Investigation of the maxillary dental arches at different development stages]. AB - Our research was carried out on maxillary casts obtained from 40 patients at prepubertal and postpubertal stages. The individuals were divided into four groups and each group consisted of 10 boys and 10 girls. The cases at prepubertal and postpubertal stages, had mixed dentitions and permanent dentitions respectively. On these casts intermolar and intercanine arch width, arch length, ratio, palatal vault depth and palatal volume measurements were performed. In the maxillary dental arch, the changes associated with the development in both sexes and the differences between the sexes with respect to the measurements were evaluated by paired t-test. The correlation of these measurements were also analysed. Consequently our findings were evaluated in the light of recent publications in the literature. PMID- 2104054 TI - [Humoral immunity in early onset periodontitis]. AB - Prepubertal Periodontitis, Juvenile Periodontitis and Rapidly Progressive Periodontitis were grouped under a single title, Early-Onset Periodontitis. These diseases were affecting the patient at a very early age and the prognosis might be an edentolous mouth. The diseases had specific host response defects. Our study was planned to study the humoral immunity of this kind of patients. PMID- 2104055 TI - [Evaluation of stresses in different cingulum rest seats]. AB - Both lingual and incisal rest seats are used on anterior teeth. Lingual rest seats are preferred since they are more acceptable esthetically and located closer to the centre of rotation of the tooth. Lingual rest seats can be prepared directly on the abutment teeth as grooves, shoulders or may require restorations such as crowns, inlays and prefabricated rest seats to provide proper contour. In this study, the stress induced by two conventionally applied rest seats were compared with that of the U shaped rest seats which were recently induced. As a result it is found that more uniform stress distribution occurred in U and inverted "v" type rest seat designs. PMID- 2104056 TI - [PH changes of different cements]. AB - Some properties are required in dental cements used in fixed restorations. One of them is the acidic characteristic of the material since (OH)- ions released during the setting phase may have undesirable effects on the pulp. In this study three different luting cements were tested regarding to their PH values during setting reaction and was found that cements used caused PH changes. Acidity of cements had changed considerably depending upon time and it was determined that PH values of three cements decreased in the period of 24 hours. PMID- 2104057 TI - [Heat changes in the gingival region of both upper and lower incisor-bicuspid and molar teeth: comparative study of healthy persons and patients who have gingivitis]. AB - In this research, total of 12 persons, 7 women and 5 men, 21-24 ages were tested. Gingival index, Greene and Vermilion simplified oral hygiene index and sulcus depth measurements were determined for both groups, local heat changes were measured in upper and lower vestibular, lingual and or palatinal keratinized gingival mucosa. According to the results, in the patient group, upper heat levels were found higher than lower levels. But only in the anterior region, the difference was statistically significant (p less than 0.05). Local heat changes were found higher in the patient group than the control group for all areas but the difference was not statistically significant. PMID- 2104058 TI - [Investigation of the castings marginal adaptation using investment expansion methods]. AB - The research in the field of metal casting has recorded a continual progress in dentistry. Particularly, due to the economic problems posed by the use of gold alloys relatively inexpensive metal alloys tend to gain increased popularity. Application of such alloys physically in dentistry and their adaptability to various preparations are being studied. In castings where investment expansion methods are employed, and marginal adaptability of castings are evaluated, the results of variance analysis have indicated little significant difference due to the applied methods. However, the hygroscopic method has proved highly successful in terms of marginal adaptability. PMID- 2104059 TI - [Thermal expansion of dental alloys and porcelains]. AB - Thermal behaviour of metal and porcelain against heat is an important factor in metal-porcelain bonding. For this reason thermal compatibility and the thermal expansion of metal and porcelain are some of the important subjects to be studied carefully. In this study, by means of dilatometric measurements, we determined the thermal expansion coefficients of metal alloy (Ivotect P) and porcelain (ITS HTE, Ivoclar) which we use in routine practice. As a result we found that the porcelain has a nonlinear expansion as oppose to metal alloy and also the firing conditions affect the thermal expansion. In addition we observed that the thermal expansion coefficient of metal alloy had changed very little in repeated castings. PMID- 2104060 TI - [Comparison of investment expansion methods aspect of porosity]. AB - Currently, the use of non-precious metal alloys in fixed prosthetic restorations has warranted review of the work done sofar using precious metal alloys. One of the parameters exhibiting the success of castings done using non-precious metal alloys is porosity, which is evaluated through such methods as rod forms, waxing heat, to investing and other castability methods. The porosity ratios of cats similarly done employing different investment expansion methods have been evaluated. While there is no statistical difference due to different methods, the hygroscopic expansion method noted successful results. PMID- 2104061 TI - [Oral bacterial flora of dogs]. AB - To be used as a model in dental and medical research, an animal must fulfil experimental needs and information on the composition and variation of its oral flora must be available. Only limited data are available on the indigenous oral bacterial flora of dogs. In this research, a total of 100 isolates from the same sites of the oral cavities of dogs were identified. Only 17 different species were isolated. The predominant species of the total cultivable flora were Staphylococcus (coagulase +, and - types), and E. coli species. This is thought to be occurred as a result of constant licking habit of these animals. PMID- 2104062 TI - [In vivo adhesion of Streptococcus mutans on amalgam and composite restorative materials]. AB - The adherence of cariogenic S. mutans, to dental restorative materials in vitro has been reported previously. The purpose of this study was to evaluate the ability of S. mutans, to colonize on metallic and nonmetallic composite restorative materials in vivo. A total of 30 plaque samples from patients with metallic restorations, and 30 plaque samples from the patients with nonmetallic restorations obtained. This study indicates that, composite restorative materials and unpolished surfaces tend to be more highly colonized by S. mutans, than metallic and polished surfaces. PMID- 2104063 TI - [The levels of alpha-1-antitrypsin in the periapical cyst lesions]. AB - Alpha-1-antitrypsin (AAT) is a serum protease inhibitor, with a well established role in bodily defense against destructive inflammatory disease. In order to investigate the role of this protease inhibitor in the periapical lesions, 13 patients were investigated. Serum alpha-1-antitrypsin levels of 13 patients were 871.8 +/- 73.6 mg/dl whereas 296.6 +/- 32.6 mg/dl in the control group. Difference was important between both groups (P less than 0.01). Alpha-1 antitrypsin levels were 40.2 +/- 13.7 mg/dl in the cyst fluid. Although the alpha 1-antitrypsin levels in the patients serum were elevated, it was not found in sufficient levels in the cyst fluid. This results suggest that, the regulation of proteolytic activity afforded by AAT, plays an important role in the pathogenesis of periapical lesions. PMID- 2104064 TI - [Analysis of stresses in modified resin-bonded cast fixed partial dentures]. AB - In 1973, ROCHETTE introduced a periodontal splinting method that involved bonding of cast perforated retainers to the acid etched lingual surfaces of anterior teeth, using a resin. Nowadays, there have been a number of reports on the clinical performance of the adhesive bridges. The objective of this investigation was to photoelastically evaluate the forces exerted on the supporting structures of abutment teeth by modified resin-bonded cast fixed partial dentures. Four modified designs were tested and a traditional fixed bridge used as a control design. This study indicated that the resin bonded cast fixed partial denture with the lingual chamfer margin and mesial rest was the design to be chosen. PMID- 2104065 TI - [An evaluation of the bond strength of plastic teeth to acrylic denture base material]. AB - Plastic teeth are preferred as functional portions with acrylic denture base material. The resin teeth have become the integral part of the denture by their chemical bonding with the base. But several factors effect the bonding: faulty boil-out procedures, residual wax on ridge-laps of the teeth, careless application of tin-foil substitutes to the teeth. On the other hand, grinding the glossy ridge-lap surface, painting the teeth with monomer or a solvent, preparing retention grooves on the ridge-lap portion of the teeth effectively lock the teeth to the denture base. The purpose of this research was to evaluate the bond strengths of the acrylic resin teeth and denture base material with retention grooves on the ridge-lap portion of the teeth. As a result of this study, bond strength between resin teeth and the denture base material is increased by the mechanical retention applied on the ridge-lap portion of the teeth. PMID- 2104066 TI - Electroencephalographic (EEG) video monitoring. AB - Electroencephalographic (EEG) video monitoring is the simultaneous documentation of the clinical and electroencephalographic manifestations of seizures. The video recording permits repeated viewing of the clinical sequence and enables comparisons with recordings of known seizures. Epilepsy is a clinical diagnosis in which most cases can be characterized with the standard clinical history, examination, and EEG. Studies of the treatment of intractable seizures (unsatisfactory control of seizure) indicate that more complex cases may require the data obtained with EEG video monitoring. For patients with intractable seizures, EEG video monitoring may help to confirm or support a diagnosis of epilepsy or confirm or support a differential diagnosis of physiologic or psychogenic seizures (nonepileptic attacks) from epilepsy. Monitoring also may provide a more accurate classification of the epileptic seizures and, for patients evaluated for surgical treatment, establish clinical focality. Estimates of the percentage of epilepsy patients requiring EEG video monitoring range from 5 to 30 percent. The average length of monitoring is approximately 10 to 16 days. In some cases outpatient monitoring in conjunction with activation procedures provides patient evaluation in only 6 to 8 hours. PMID- 2104067 TI - Carotid endarterectomy. AB - Carotid endarterectomy is a surgical procedure to remove atherosclerotic occlusions from the carotid artery. The surgery is usually performed in patients with transient ischemic attacks (TIAs), asymptomatic stenosis, or stroke in order to reduce stroke risk and increase cerebral blood flow. Complication rates vary widely among surgeons and hospitals, and numerous studies testing the efficacy of carotid endarterectomy and documenting its associated morbidity and mortality have produced conflicting or inconclusive results. No properly designed prospective clinical trial has convincingly demonstrated this surgery to be superior or inferior to nonoperative management for any subset of patients with carotid artery disease. There has been no definitive study concluding that patients with TIA benefit from carotid endarterectomy. The benefits for asymptomatic patients are even less clear. Among the alternative surgical and medical treatments advocated for occlusive carotid disease, none has clearly demonstrated superior therapeutic results. It is generally agreed that current ongoing prospective, randomized, controlled clinical trials are likely to provide the data required for determination of optimal therapy and better identify subsets of patients who are most likely to benefit from carotid endarterectomy. Until the results of these clinical trials become available, the proposed benefits of carotid endarterectomy must be regarded as indeterminate. PMID- 2104068 TI - Screening elderly people. PMID- 2104069 TI - Review article: bile acid therapy. AB - Over the past 3 years there has been a renewed interest in bile acid therapy not only because of the promising results obtained by combining this therapy with extracorporeal shock-wave lithotripsy for rapid gallstone dissolution, but also because of its novel use as a treatment for primary biliary cirrhosis. This article reviews the use of bile acids for both these indications. PMID- 2104070 TI - Making mesmerizing statements ... (about the toxic effects of anti-ulcer drugs, such as bismuth-containing preparations) PMID- 2104071 TI - The value of flumazenil in the reversal of midazolam-induced sedation for upper gastrointestinal endoscopy. AB - Fifty patients who underwent diagnostic upper gastrointestinal endoscopy after midazolam sedation were randomized to receive (after completion of the examination) either the benzodiazepine receptor antagonist flumazenil or an identical-looking placebo. The speed of recovery from sedation was assessed by reaction time testing, measurement of critical flicker fusion frequency, and the semi-quantitative SOCA scoring system. Measurements were made up to 6 h post examination in all subjects, and at 12 and 24 h in all in-patients (n = 20). Flumazenil-treated patients were significantly more alert than those who received placebo at 10 min, 30 min, 1 h and 2 h (P less than 0.001 in all instances). Thereafter the two groups were similar. There was no evidence of recurrence of sedation in flumazenil-treated patients, nor did this drug adversely affect the period of anterograde amnesia between the administration of midazolam and flumazenil. PMID- 2104072 TI - Rapid intravenous low-dose diazepam as sedation for upper gastrointestinal endoscopy. AB - One hundred patients for endoscopy, aged, between 18 and 74 years were randomly allocated to two equal groups. Group A received 10 mg diazepam intravenously rapidly over 2-4 s; Group B received diazepam intravenously over 1-2 min, titrated to provide a satisfactory level of sedation (mean dose 15.9 mg). Patient co-operation during endoscopy was similar in both groups, but one patient in Group A developed respiratory depression. Tests of psychomotor function after endoscopy showed greater impairment 30 min following injection for Group B, compared with Group A (P less than 0.02). Total or partial amnesia for endoscopy was present in 62% of Group A, and 90% in Group B (P less than 0.005). However, postal follow-up showed that endoscopy was acceptable to 96% of Group A and 98% of Group B. Delayed sedation later in the day was reported by 26% of Group A compared with 48% of Group B. PMID- 2104073 TI - Dosage of colloidal bismuth subcitrate in duodenal ulcer healing and clearance of Campylobacter pylori. AB - Sixty consecutive patients with endoscopically proven duodenal ulcers were given colloidal bismuth subcitrate tablets either as 120 mg q.d.s. or 240 mg b.d., in a randomized single-blind study. The efficacy of each regimen was determined by endoscopic examination and antral biopsy at 4 weeks; if the ulcer remained unhealed, treatment was continued and endoscopy repeated at 8 weeks. The ulcer healing efficacy of the two regimens was identical; however, in the four times daily group only 27% remained Campylobacter pylori positive after 8 weeks of treatment compared with 58% of the twice-daily group. Similarly, only 21% of twice daily patients were free of histological gastritis compared with 42% of the four times daily patients. PMID- 2104074 TI - Coated oral 5-aminosalicylic acid versus placebo in maintaining remission of inactive Crohn's disease. International Mesalazine Study Group. AB - A randomized, double-blind, placebo-controlled multicentre study was undertaken to evaluate the safety and efficacy of coated, oral 5-aminosalicylic acid (Mesasal/Claversal; 5-ASA) in maintaining remission of inactive Crohn's disease for up to 12 months. A total of 248 patients were entered from eight countries, of which 206 adhered to the protocol and were included in the analysis. The patients had Crohn's disease for an average of 5 years, with their disease clinically inactive for at least 1 month prior to entry into the study, and for an average of over 12 months previously. Thirty per cent of patients had had a previous resection, 16% of patients had been treated with sulphasalazine, while none of those analysed received glucocorticosteroids. Treatment consisted of 500 mg 5-ASA t.d.s. or placebo. 'Relapse' was defined as the first occurrence of Best's Crohn's Disease Activity Index greater than 150, which had increased 60 points from the pre-trial index. The cumulative life-table relapse estimate was lower in 5-ASA patients compared to placebo (22.4% vs 36.2%, respectively, Log rank test P = 0.0395). The 12-month relapse estimate in the 5-ASA group was also lower in patients with ileal disease (8.3% for 5-ASA and 31.0% for placebo, P = 0.0535) and in patients with previous bowel resections (14.2% vs 47.0%, P = 0.0436). The incidence of side-effects was similar in both treatment groups. It is concluded that 5-ASA was significantly superior to placebo in preventing relapse of Crohn's disease; this effect was most apparent in patients with disease restricted to the ileum and in patients with previous bowel resection. 5 ASA was well-tolerated, as demonstrated by a low incidence of adverse events. PMID- 2104075 TI - Intravenous omeprazole: effect of a loading dose on 24-h intragastric pH. AB - To determine the effect of three times daily dosing with intravenous omeprazole on intragastric acidity, 24 h intragastric pH was measured continuously with a monocrystalline antimony electrode system in II patients with inactive duodenal ulceration during fasting conditions. After a baseline investigation, two different dosage regimens of intravenous omeprazole were compared in a double blind crossover study, with regard to their ability to keep the pH greater than or equal to 4 for as long as possible. Success in the individual patient was defined as pH greater than or equal to 4 for at least 90% over the 24-h period. Two doses of omeprazole [40 mg t.d.s. (120 mg) and 80 mg + 40 mg + 40 mg (160 mg)] were compared. Omeprazole (120 mg) increased the median of individual median intragastric 24-h pH from 1.49 to 6.67. The pH was greater than or equal to 4 for greater than or equal to 90% of the 24 h in three of the 11 patients. With omeprazole, 160 mg (a loading dose of 80 mg), the median of individual median intragastric 24-h pH increased to 7.33. The pH was greater than or equal to 4 for greater than or equal to 90% of the 24 h in seven of the 11 patients. Median time to reach pH 4 was 39 min after 40 mg and 20 min after 80 mg omeprazole. An initial loading dose of 80 mg omeprazole seems preferable to 40 mg to achieve a fast and sustained increase in intragastric pH to above 4 in the fasting patient. PMID- 2104076 TI - Pharmacokinetics of famotidine in normal subjects and in patients with chronic liver disease. AB - The pharmacokinetics of famotidine were studied in seven healthy control subjects and in 14 patients with cirrhosis, following single oral and intravenous 20-mg dose administration, and after seven daily doses of 40 mg. Following intravenous (i.v.) administration, the mean (range) total plasma clearance values were not significantly different in the patients with compensated cirrhosis (n = 7), 337 (241-576) ml/min or in the patients with decompensated cirrhosis (n = 7), 270 (120-408) ml/min compared with the control group, 370 (154-612) ml/min. The mean half-life in the compensated cirrhotics, 2.86 (1.87-4.98) h, was similar to that in the control group 2.91 (1.86-6.03) h, but it was insignificantly prolonged in the decompensated cirrhotics 3.35 (2.00-5.77) h. The mean, maximum, plasma famotidine concentrations after single oral doses were comparable between the groups but there was considerable inter-subject variability, with individual values ranging from 17 to 139 ng/ml. Peak plasma concentrations were reached within 2-3 h, although more variability was observed among patients with decompensated cirrhosis. The mean systemic availability of the drug, estimated from urinary recovery, was 0.39 (0.15-0.64) in the healthy controls, 0.35 (0.14 0.51) in the patients with compensated cirrhosis and 0.38 (0.13-0.77) in the patients with decompensated cirrhosis. No significant increases were observed in plasma trough famotidine concentrations following multiple oral dosing in any of the subjects, and the kinetic variables after the seventh dose were not significantly different from those following the single oral dose. No significant changes were observed in psychometric performance in control subjects or in patients between the pre-study day and day seven of the multiple oral dose phase. PMID- 2104077 TI - Duodenal ulcer healing on 2 g of sucralfate daily at bedtime compared to 1 g four times daily. AB - Seventy-seven patients with endoscopically verified duodenal ulcers were randomized to treatment with either 2 g sucralfate daily at bedtime or 1 g sucralfate q.d.s. in a controlled double-blind comparative study. After a 4-week treatment period, the healing rate was 68% for the former and 69% for the latter treatment. PMID- 2104078 TI - Review article: premedication and intravenous sedation for upper gastrointestinal endoscopy. AB - Upper gastrointestinal endoscopy can be performed without intravenous sedation but the evidence suggests that, in the United Kingdom and United States, most patients and endoscopists prefer that some form of premedication is given. Intravenous diazepam or midazolam are used by the majority of endoscopists. In the UK, the ratio of diazepam to midazolam users is approximately 2:1, while in the USA more endoscopists are now using midazolam. Midazolam is approximately twice as potent as diazepam but, when allowance is made for this, there is probably little or no difference in the propensity of the two drugs to produce respiratory depression. The antegrade amnesic effect of midazolam is significantly superior to that of diazepam. A benzodiazepine/narcotic combination can achieve a smoother and more rapid induction with less gagging and choking, but the incidence of adverse outcomes--particularly respiratory depression--is increased significantly. Over 50% of the deaths that are associated with upper gastrointestinal endoscopy are due to cardiopulmonary problems. Hypoxia is very common if measured using non-invasive monitoring equipment, such as a pulse oximeter. Methods of preventing oxygen desaturation and thus, by inference, most cardiac arrhythmias associated with endoscopy are discussed, as is the role of flumazenil, the new benzodiazepine antagonist. PMID- 2104079 TI - The efficacy of tobramycin in the treatment of ulcerative colitis. AB - This paper reports a double-blind placebo-controlled trial of oral tobramycin in acute ulcerative colitis. Eighty-four patients with an acute relapse of ulcerative colitis were randomized to receive oral tobramycin or placebo for 1 week as an adjunct to steroid therapy. At endpoint, 31 of 42 (74%) in the tobramycin group achieved complete symptomatic remission compared with 18 of 42 (43%) in the placebo group (P = 0.008). The tobramycin group achieved better histological scores (P less than 0.05) at endpoint. These findings show that treatment with oral tobramycin improves the short-term outcome of patients with ulcerative colitis in relapse. PMID- 2104080 TI - Serum gastrin levels during long-term omeprazole treatment. AB - Serum gastrin was determined in 33 patients during treatment with the proton pump inhibitor omeprazole. After 4 weeks of therapy, gastrin levels increased to a median of 55 pg/ml compared to 15 pg/ml prior to omeprazole (P less than 0.001). There was a close correlation (r = 0.939; P less than 0.001) between pre treatment gastrin and levels at 4 weeks. Comparison of serum gastrin concentrations at 1 month of omeprazole with levels at 6 (n = 21) and 12 months (n = 12) continuous therapy revealed a close correlation (r = 0.961 and r = 0.882, respectively; P less than 0.001) despite dose adjustment. In marked hypochlorhydria documented by continuous pH monitoring, serum gastrin varied from normal up to profound hypergastrinaemia. These results demonstrate that the serum gastrin increase under powerful acid-inhibitory drug therapy depends upon a number of variables. (a) Only in patients with elevated gastrin levels, prior to omeprazole treatment, can moderate to marked hypergastrinaemia during omeprazole be expected. (b) Gastrin increases reached during the initial period of omeprazole treatment remain constant during long-term therapy. (c) Acid inhibition itself is not necessarily associated with an increase in serum gastrin in every patient, which suggests that the individual sensitivity of the gastrin cell to acid inhibition is more important for serum gastrin changes than the degree of acid inhibition itself. PMID- 2104081 TI - The safety and efficacy of tripotassium dicitrato bismuthate (De-Nol) maintenance therapy in patients with duodenal ulceration. AB - Seventy-one patients whose duodenal ulcers had healed after a 4-week treatment period with tripotassium dicitrato bismuthate (TDB) were randomly allocated to receive maintenance treatment with either one TDB swallow tablet nocte (equivalent to 120 mg Bi2O3) or an identical placebo. During 12 months of follow up, no side-effects were reported by TDB-treated patients, blood bismuth levels did not rise above discontinuation threshold concentrations (greater than 50 micrograms/L in the first 6 months, or greater than 100 micrograms/L in the second 6 months), and there were no adverse effects on haematological or biochemical indices. Ulcer relapse was significantly less in TDB-treated patients (P less than 0.025). Cumulative relapse rates at 6 and 12 months were 51% and 66%, respectively, for placebo-treated patients and 26% and 31%, respectively, for those who received TDB. It is likely that TDB is a safe and effective maintenance treatment for patients with duodenal ulcer disease. PMID- 2104082 TI - The absorption of bismuth and salicylate from oral doses of Pepto-Bismol (bismuth salicylate). AB - Plasma bismuth and plasma salicylate concentrations were measured before and after three 30-ml oral doses of bismuth salicylate (Pepto-Bismol liquid) in 10 fasting healthy subjects. From 0 to 120 min following the first dose of bismuth salicylate, the plasma bismuth concentration was less than 1 ng/ml. The peak median plasma bismuth concentration was at +240 min (1.7 ng/ml; range 0.8-5.3 ng/ml). Salicylate appeared in the plasma of all subjects at +30 min, and it reached a peak at +120 min (median 61 mg/L; range 46-104 mg/L). The study demonstrates that, despite rapid and substantial absorption of salicylate, there is negligible absorption of bismuth into the bloodstream from standard oral doses of bismuth salicylate. PMID- 2104083 TI - Effect of ranitidine and indomethacin on nocturnal gastric acidity in normal subjects. AB - To assess the effect of indomethacin on gastric acidity and to identify a potential pharmacodynamic interaction between indomethacin and ranitidine, we measured nocturnal acidity on half-hourly aliquots of gastric contents from 10 volunteers on the seventh day of four dosing regimens given in a randomized double-blind manner. These were indomethacin (50 mg t.d.s.) and ranitidine (300 mg in the evening) together or alone with matching placebos. Median nocturnal acidity on placebo was 41.7 mmol/L (range 67.6-25.1 mmol/L) and was 39.8 mmol/L (63.1-24.0 mmol/L) on indomethacin (N.S.). During ranitidine dosing it was 0.4 mmol/L (21.3-0.0 mmol/L) without and 0.8 mmol/L (43.7-0.0 mmol/L) with concurrent indomethacin, representing 99 and 98% decreases in gastric acidity (P less than 0.01) compared with placebo. Indomethacin did not increase overnight gastric acidity and did not influence the suppression of acidity produced by ranitidine. It is unlikely that the ulcerogenic potential of indomethacin is explicable by an effect on gastric acidity. PMID- 2104084 TI - Effect of octreotide on mouth-to-caecum transit time in healthy subjects and in the irritable bowel syndrome. AB - The effect of a single subcutaneous injection of octreotide (50 micrograms) on mouth-to-caecum transit time was determined in patients with the irritable bowel syndrome who complained of bowel frequency, and in healthy volunteers. The assessment of mouth-to-caecum transit time was performed by monitoring breath hydrogen concentration and noting a sustained 10 p.p.m. rise after ingestion of lactulose 40 ml. Measurements were performed fasting, and on a separate day, after a standard breakfast which included 40 ml lactulose. The studies were performed double-blind in a pre-determined random order. Octreotide prolonged mouth-to-caecum transit time in irritable bowel syndrome patients and healthy subjects by factors of 2.4 and 2.6 after lactulose when fasting, respectively, and by factors of 2.8 and 2.6 after the breakfast which contained lactulose. The upper gastrointestinal transit rate was similar in irritable bowel syndrome patients and healthy controls. PMID- 2104085 TI - Amino acid tolerance in cirrhotic patients following oral protein and amino acid loads. AB - Plasma amino acid and venous blood ammonia concentrations were measured in six patients with well-compensated cirrhosis and in six healthy volunteers, both in the fasting state and serially for 5 h following ingestion of 30 g mixed protein and 30 g amino acid mixture, administered on separate occasions. Mean fasting plasma concentrations of threonine, serine, proline, glycine, and of the three branched-chain amino acids, valine, isoleucine and leucine, were significantly reduced in the cirrhotic patients compared with the control subjects, while mean (+/- 1 s.d.) fasting venous blood ammonia concentrations were comparable 71.2 +/- 31.4 cf. 56.0 +/- 25.4 mumol/L. Following the oral protein and amino acid loads, increases were observed in plasma amino acid concentrations in the majority of subjects with a return to baseline values by the end of the study. Changes in the circulating concentrations of most amino acids were independent of their concentration in the oral protein and amino acid loads, and their relative distribution in the circulation varied over time. The increases in the concentrations of the three branched-chain amino acids did, however, reflect their concentrations in the two nitrogen loads and did remain constant, relative to one another, over time. There were wide intra- and inter-individual variations in plasma amino acid concentrations following protein and amino acid ingestion in both study groups, and in general no significant differences in responses were observed between them. Similarly, no significant inter-group differences were observed in the ammonia response to the two nitrogen loads. No fundamental differences exist in the ways in which patients with well-compensated cirrhosis handle oral protein or amino acid loads of the magnitude employed in the present study. PMID- 2104086 TI - Review article: hypoxia and hepatic drug metabolism--clinical implications. AB - Most major pathways of hepatic drug metabolism are dependent on oxygen. Hepatic mixed-function oxidases use oxygen directly as a substrate, while many other enzyme systems are indirectly dependent on oxygen for the generation of essential co-factors, such as NAD+ and ATP. Studies in vitro show that many of these oxygen dependent reactions are impaired by relatively minor reductions in oxygen supply, of a magnitude likely to be encountered in vivo. Phase I metabolism by mixed function oxidases appears to be more sensitive to hypoxia than phase II drug conjugation, although the oxygen requirements of conjugation reactions, such as glucuronidation, may be greatly enhanced by poor nutrition or fasting. Studies in humans are few, but in general they affirm the potential importance of the effects of hypoxaemic states on hepatic drug elimination. On present evidence, special care should be taken in hypoxic patients with drugs extensively metabolized by the liver, particularly those which have a low therapeutic ratio. PMID- 2104087 TI - Review article: metronidazole and the anaerobic gut flora. AB - Metronidazole is a nitro-imidazole drug which was discovered nearly 30 years ago. Metronidazole has remained the mainstay of anti-anaerobic therapy following a change observation that its activity included anaerobic organisms. The predominant human reservoir of these anaerobic organisms is the gastrointestinal tract. In this review, the anaerobic flora and their pathogenic potential are described. The main characteristics of metronidazole and the role of selective decontamination of the gastrointestinal tract are also discussed. PMID- 2104088 TI - Gastrointestinal pH and transit times in healthy subjects with ileostomy. AB - Gastrointestinal pH in 11 healthy subjects with ileostomy was determined with a pH-sensitive, radiotransmitting capsule. Median pH was 7.0 in duodenum, dropped to pH 6.3 in the proximal part, but rose to 7.3 in the distal part of the small intestine. In five subjects the pH of the ileostomy effluents was determined with the pH capsule as well as with a pH meter. Median pH was 7.2 measured with the capsule and 7.4 with the pH meter. The difference between the results obtained with the two methods ranged from 0.1 to 0.3 pH units. The median gastrointestinal transit time of the capsule was 10.5 h (range 6.2-12.8 h). Gastric residence time was 0.6 h (range 0.2-3.8 h), and small intestinal transit time was 10.3 h (range 5.6-11.9 h). Thus the small intestinal transit time in ileostomates is slightly increased compared with values reported from studies on subjects with intact gut. However, no statistically significant correlation was found between the small intestinal transit time and the time elapsed after the creation of the ileostomy. We conclude that colectomy does not alter small intestinal pH but seems to increase the small intestinal transit time of single units. PMID- 2104089 TI - The interaction between Helicobacter pylori culture filtrate and indomethacin: effects on the integrity of human gastric antral mucosa and its prostaglandin E2 production in vitro. AB - Histopathological methods and radioimmunoassay were used to assess the microstructure and prostaglandin E2 production by paired specimens of human gastric antral mucosa; the specimens were studied after 48 h of incubation in base-line tissue culture medium, Helicobacter pylori culture filtrate, H. pylori culture control fluid, indomethacin, and H. pylori culture filtrate plus indomethacin. When applied alone, the filtrate did not affect the structure of the mucosal tissue or its prostaglandin E2 synthesis. In the overall group (n = 21), specimens incubated with the mixture of H. pylori filtrate and indomethacin had a median histological grade of 1 and prostaglandin E2 of 29 pg/mg tissue, compared to 2 pg/mg (P = 0.04) and 60 pg/mg (P = 0.0007) respectively, in specimens incubated with indomethacin alone. These results indicate that an interaction may exist between indomethacin and a factor contained in H. pylori culture filtrate. Such interaction is damaging to the human gastric antral mucosa, and its understanding might have therapeutic implications. PMID- 2104090 TI - Twenty-four-hour intragastric acidity and nocturnal gastric secretion in gastric ulcer patients--the effects of cimetidine. AB - In a double-blind randomized study, the profile of 24-h intragastric acidity and nocturnal gastric secretion was measured in a group of patients with healed gastric ulcer on placebo and 400 mg cimetidine b.d. and 800 mg nocte. Neither cimetidine regimen significantly decreased daytime intragastric acidity, but the 800 mg nocte dose caused a significant decrease in both nocturnal acidity (18.1 to 5.5 mmol/L; P less than 0.05) and acid output (11.0 to 1.7 mmol 7 h; P less than 0.05). The decrease in nocturnal gastric secretion by 400 mg cimetidine b.d. was not significant. As in duodenal ulcer, 800 mg cimetidine nocte will effectively suppress night-time acid secretion in patients with gastric ulcer while leaving acid secretion during the day unaffected. PMID- 2104091 TI - Effect of intra-colonic nicardipine on colonic motility in irritable bowel syndrome. AB - Intravenous nicardipine has previously been shown to abolish the effect of a 1000 calorie meal on colonic motility. The purpose of this study was to use the same experimental design to assess the effect of nicardipine instilled directly into the colon. Each patient was studied three times when receiving either placebo, 15 mg or 30 mg nicardipine infused over 2 h. Blood concentrations of nicardipine remained very low, but neither dose of the drug affected either basal or post prandial colonic motility. Topical nicardipine does not appear to have therapeutic potential and its activity is probably dependent on systemic absorption. PMID- 2104092 TI - The value of flumazenil in the reversal of midazolam-induced sedation for upper gastrointestinal endoscopy. PMID- 2104093 TI - [Chronic fatigue syndrome]. PMID- 2104094 TI - [Effect of thyroidectomy on bone mineral metabolism. Experimental study in rats]. AB - The aim of the study was to ascertain the importance of calcitonin in the etiopathogenesis of osteoporosis in rats as an animal model. We used 20 female rats on which a thyroidectomy was performed, producing a calcitonin deficit. An autologous transplant of parathyroid gland and replacement therapy of thyroid hormone was carried out. The control group consisted of 20 rats. The levels of parathormone (PTH), calcitonin (CT), osteocalcin (GLA), seric calcium, and density, weight, quantity and mineral bone content of the head of the femur were measured. We found low levels of CT and normal amount of PTH, which contradicted the expected, there was an increment of the mineral bone content, without significant density, quantity and weight changes. We comment on these results. PMID- 2104095 TI - [Hepatitis B virus (HBV) replication in patients with various types of chronic hepatopathy]. AB - We study retrospectively the viral replication state (HBV) of 50 patients with chronic hepatic alterations. The seric DNA-HBV and/or intrahepatic (molecular hybridization), the intrahepatic distribution of HBV antigens (specific monoclonal antibodies labelled with immunoperoxidase), conventional seric HBV markers (commercial enzymoimmunoessay) and the different histopathologic features. We found a correlation between DNA-HBV "in situ" and HBcAg intrahepatic and the seric DNA-HBV production. 81% of the patients with HBsAg (+) had intrahepatic HBcAg and 85% (11/13) of them showed the antigen in their cytoplasms. Patients with HBcAg also had seric and liver DNA-HBV (+). The lack of seric HBsAg did not mean that non-active replication of HBV did not exist because 20% of the patients with HBsAg (-) showed seric and "in situ" DNA-HBV and cytoplasmic HBcAg. The detection of DNA-HBV in endothelial cells and vascular elements in hepatic tissue show that the rate of the HBV host cells is greater. PMID- 2104096 TI - [Coxiella burnetii: serologic study in various populations]. AB - Complement binding antibodies against Coxiella burnetii were measured in 699 seric samples in order to ascertain the possible relationship between seric prevalence and the following factors: age, sex, living in rural or urban areas and socio-economical level. All patients were healthy: 180 were from a rural area 86 from Guijo (Caceres); 36 from Chiloeches (Guadalajara) and 58 from Bustarviejo (Madrid); 519 were from an urban area (City of Madrid). The samples from Madrid city were classified by socio-economical level: 386 from medium-low level (MLL) and 133 from medium-high socio-economical (MHL) level. The global seroprevalence was 32.3%, being 46.1% from rural areas; --59.3 from Guijo, 33.3% from Chiloeches and 34.5% from Bustarviejo. In urban areas the seroprevalence was 27.5% this being 30.8% MLL and 18% MHL. We found a statistically significant relationship between both socio-economical levels and the area of living. PMID- 2104097 TI - [Changes in blood viscosity and erythrocyte deformability in patients with dyslipidemia treated with binifibrate]. AB - 31 patients afflicted with primary hyperlipidemia who did not improve after 30 days on a diet were treated with 1800 mg/day of binifibrate. We measured the total cholesterol level and triglyceridemia, as well as blood viscosity and red cell deformability at day 0, 30, 60, 90 of treatment. We found a statistically significant decrease in cholesterol and triglyceride levels as well as blood viscosity, and an increment of red cell deformability which improved the circulatory dynamisms augmentin the tissular perfusion in these patients. PMID- 2104098 TI - [Obstructive uropathy as initial manifestation of Crohn disease]. AB - A patient with renal colicky pain caused by urinary tract obstruction, as a result of psoas abscess, is presented. It was the first manifestation of Crohn's disease. A Gram negative bacteria was isolated from the abscess. The CT images performed to evaluate the abscess suggested this etiology, even though there were no previous symptoms. PMID- 2104099 TI - [Possible cardiotoxicity induced by orally administered fluoropyrimidines]. AB - 4 more cases of cardiotoxicity associated to 5-FU or oral fluoropirimidine (Ptorafur, UFT) in patients without previous heart disease (except in one case) are presented. The toxicity found was myocardial ischemia and EKG changes (in 3 patients) in patients whose enzymes were measured. The etiopathogenesis and features of this toxicity are discussed. PMID- 2104100 TI - [Pseudomeningocele after laminectomy]. AB - Pseudo-meningocele post-laminectomy is a non-frequent complication of this surgical technique. It is usually diagnosed by myelography; the CT scan has helped to detect more cases. We present a case studied by CT and RMN and there are no existing previous publications on the case confirmed by RMN. The relation between the findings and the clinic as well as the therapy still on discussion. PMID- 2104101 TI - [Usefulness of bone remodelling biochemical markers in the diagnosis and follow up of Paget's bone disease, primary hyperparathyroidism, tumor hypercalcemia, and postmenopausal osteoporosis. II. Bone resorption markers]. AB - Rapid detection of the exact changes in bone remodelling is exceptionally important. In this paper, the latest bone remodelling biochemical markers are reviewed. Some of them have already been used for a long time, and their utility has been widely demonstrated. The newest ones, in experimental stage, can be used as a complement to the others. The bone remodelling markers reviewed are: 1) Alkaline phosphatase; 2) osteocalcin; 3) other noncollagen of bone matrix such as osteonectin, GLA-protein of the matrix, osteopontine and alpha 2-HS-glycoprotein; 4) Procollagenous and other collagenous peptides of the matrix (C terminal of type I procollagen and urinary elimination of non-dialysis hydroxyproline. Amongst the bone resorption markers studied are: 1) Calcium/creatinine urinary quotient; 2) Tartrate resistant acid phosphatase; 3) Urinary hydroxyproline; 4) Other substance derived from collagen disruption such as hydroxylysine glycoside, piridinolinic intermolecular bridges and the enzymatic activity of proline iminopeptidase. We endeavored to collect all the most important references on the matter, especially those relating to Paget's disease of the bone, primary hyperparathyroidism, tumoral hypercalcemia and postmenopausal osteoporosis. PMID- 2104102 TI - [The kidney in ankylosing spondylitis]. PMID- 2104103 TI - [Pneumomediastinum complicating pleurodesis caused by tetracycline chlorhydrate]. PMID- 2104104 TI - [Pancytopenia as the first manifestation of Felty's syndrome]. PMID- 2104105 TI - [Peripheral arthritis, cavitated nodule initially thought to be of tuberculosis origin, and denial of drug dependence. Important difficulties to diagnose infective endocarditis in a drug addict]. PMID- 2104106 TI - [Trigeminal neuralgia as the first manifestation of craniopharyngioma]. PMID- 2104107 TI - [Adult Still's disease. Report of a case]. PMID- 2104108 TI - [Septic oligoarthritis caused by Staphylococcus aureus in a patient with prostatic adenocarcinoma]. PMID- 2104109 TI - [Can flumazenil counteract the central effects of alcohol?]. PMID- 2104110 TI - [Temporal arteritis and pericardial effusion]. PMID- 2104111 TI - [Tremor as initial manifestation of neurobrucellosis]. PMID- 2104112 TI - [Tuberculosis and HIV infection]. PMID- 2104113 TI - [Osteoporosis]. PMID- 2104114 TI - [Tuberculosis in Leon. An epidemiological approach]. AB - The aim of the present study was an approach to the epidemiological status of tuberculosis in the Leon province. To this end, we studied the morbidity through the EDOs and we carried out two tuberculin surveys during 1988-1989 to assess RAI. The results showed infection prevalences of 1.19 and 1.09 at six years of age for the two study years, respectively, with a RAI between 0.118 and 0.079. We conclude that tuberculosis still is an important health problem. The RAI indicates that our level is that of a developed country. We also discuss the supposed increase in the frequency of tuberculosis. PMID- 2104115 TI - [Vaccination every time when an occasion arises: evaluation of an intervention in the Murcia Autonomous Community]. AB - This study evaluated the occasions for vaccination that are lost in a vaccination center by means of the systematic offer of tetanus vaccine to the adults which accompanied pediatric patients. The study was prospective and had three periods, of two weeks duration each. In the first period vaccination was offered through a questionnaire, in the second without questionnaire, and the third was used as control. The recorded accompanying persons were 298, 478 and 155 for the three periods. During the first period the overall number of administered doses increased by 22%. During the second it increased by 31% (p = NS). In both the number of administered tetanus vaccine doses was doubled. 68% of the nonvaccinated accompanying persons accepted the vaccine in the first period, and 63% in the second period (p = NS). We conclude that both intervention alternatives were equally effective. Through this intervention we increased the rate of adequately vaccinated accompanying persons form 30 +/- 3% to 75 +/- 3%. This approach may be effective to increase the level of tetanus immunization in the adult population when applied in primary care centers. PMID- 2104116 TI - [Study of preventive activity and health promotion in a primary care center]. AB - The present study was undertaken in our center to investigate the application level of the criteria from the Program of Preventive Activities and Health Promotion (PAPPS) for the adult population of the SEMFYC, before the implementation of any specific activity. We carried out a simple random sampling (310 clinical records) and we registered their application for risk subpopulations. The most relevant results were as follows: screening for hypercholesterolemia 41.4%, for hypertension 27.2%, for smoking habits 45.8%, for chronic alcohol abuse 35.2%, and for obesity 13.6%. Those corresponding to women program and vaccinations were poor, except for influenza vaccination (39.7%). We evaluate the small preventive activity and its low effectiveness, which is related to the lack of protocols, of an adequate population ranging and of integrated approach. We conclude that there is a need for protocol approach and a population-oriented program of preventive activity, with an adequate recording system. We expect to achieve these goals by the adscription of the EAP to PAPPS. PMID- 2104117 TI - [Chronic theophylline treatment in chronic airflow obstruction. Relations between doses, blood levels and expiratory flow]. AB - We evaluated 31 patients from the ABS La Gavarra in Cornella de Llobregat who fulfilled the following criteria: they were male, they had mild to moderate chronic limitation to airflow (CLAF), their disease and/or other accompanying conditions were stable, and they were receiving chronic slow release theophylline therapy. We investigated theophylline blood levels in these patients, attempting to correct the doses when appropriate, and we correlated the therapeutic levels with the subjective clinical improvement, which was also assessed by peak flow meter values. A total of 60% of patients had therapeutic levels. After correcting the dose, 64% had therapeutic levels with an increase of spirometric values of 4%. This improvement has small clinical relevance as it does not reach the expected 15%. The results of this study help to reassess the leading role of theophyllines in the therapeutic armamentarium available for CLAF. PMID- 2104118 TI - [Evaluation of the degree of compliance in arterial hypertension protocol]. AB - We report an evaluation of the hypertension protocol. Its aims were to assess the degree of compliance with its variables, the number, age and sex of hypertensives, and the rate in whom blood pressure levels were controlled in the patients included and not included in the protocol. The study was carried out in the Basauri Teaching Unit from January 1987 to June 1989. We reviewed all the parameters of the medical and nursing protocol of 1,429 patients diagnosed as hypertensive and the mean value of the three last blood pressure readings. A total of 67.2% of patients were included in the protocol. The compliance was higher than 80% in most of its items; 61.8% of the prescribed nursing controls were carried out. Blood pressure was less than or equal to 159/94 in 68.1% of patients. This rate was higher in the patients included in the protocol. The protocol was useful for the control of hypertension, although it should be modified directing it to primary care. PMID- 2104119 TI - [Level of knowledge among medical students about hypercholesterolemia]. AB - The general practitioner plays a fundamental role in the control of hypercholesterolemia as a risk factor of atherosclerosis; therefore, education about this issue should be an important part of the undergraduate curriculum. Thus, we carried out the present study to investigate whether the curriculum in our medical schools provides the necessary knowledge to the primary care physician to carry out this function. To this end, we distributed a questionnaire to 585 medical students of different years in the Cordoba School of Medicine. Most students have a clear idea of the importance of cardiovascular disease as a cause of death. The level of knowledge about basic pathogenetic aspects of plasma lipoproteins is considerable. The students are acquainted with the adequate dietary interventions for the management of the patient with hypercholesterolemia, and they learn the advantages of consuming blue fish and olive oil. However, the level of knowledge about drug therapy is disappointing. Finally, most of them declared to be in favour of a personal approach to the prevention of atherosclerosis with diet. We conclude that the overall level of knowledge and personal approach of the students of that particular School of Medicine permits an optimistic view in the field of prevention of coronary atherosclerosis. PMID- 2104120 TI - [Study on incidence and validity of questionnaire in the diagnosis of oxyuriasis]. AB - Oxyuriasis is one of the commonest infestations in our area, with rates ranging from 5% to 75% in several studies. The present study was carried out in 100% of schoolchildren in a rural town with a population of 1,000 in the Lerida province. The study had two parts. On the one side, the prevalence of oxyuriasis was evaluated with Graham's test; on the other side, a self administered questionnaire was distributed to assess the validity of the surveyed symptoms for the diagnosis of oxyuriasis. The results disclosed a 59.5% prevalence, which was somewhat higher in girls than in boys. The study of diagnostic validity showed that the only symptom with a high yield was the anal and/or genital pruritus. The remaining symptoms could be discarded due to their low reliability. PMID- 2104121 TI - [Multiple sclerosis. A primary care approach]. AB - We report five cases of multiple sclerosis (MS), diagnosed in the population cared for in a primary care center. We assess the different forms of presentation and outcome, making practical suggestions for the diagnosis and follow up in a primary care setting. PMID- 2104122 TI - [Changes in the proteinogram]. PMID- 2104123 TI - [Recommendations how to prevent mistakes in statistical analysis of a clinical study]. PMID- 2104124 TI - [Do very low frequency magnetic fields have a deleterious influence in humans?]. PMID- 2104125 TI - [Postherpetic facial paralysis]. PMID- 2104126 TI - [Importance of the social milieu in the diagnostic and therapeutic approach in primary care]. PMID- 2104127 TI - [Attitude of specialists to their family and community medicine specialty: a failure of the educational system?]. PMID- 2104128 TI - [Urinary infection in primary health care: bacteriology and treatment with single dose of trimethoprim]. PMID- 2104129 TI - [Referral by a primary health center to the emergency service of the reference hospital]. PMID- 2104130 TI - [Gingival hyperplasia and nifedipine]. PMID- 2104131 TI - [The preference for the final digits in blood pressure determination: a continuing education experience]. AB - The CRONICAT program is developing a Project for the Control of Hypertension in three areas of central Catalonia. In the analysis of the blood pressure data of the registry of patients from this project, carried out 18 months after its beginning, it was found that a high proportion of blood pressure (BP) readings showed 0 or 5 as the terminal digit (57.3% and 16.6% in diastolic BP, and 66.6% and 11.8% in systolic BP, respectively). To improve the quality of the reading two continuing education activities were carried out; a seminar where a practical session of blood pressure measurement was developed, using a videotape with 12 BP recordings permitting to see the interobserver and intraobserver variability, and discussion meetings with all the primary care teams which participate in the Project. 36 months after the beginning a new analysis of data was carried out, and it was found that the preference for 0 and 5 had decreased to 41.1% and 7.5% for diastolic BP and to 51.3% and 8.2% for had decreased to 41.1% and 7.5% for diastolic BP and to 51.3% and 8.2% for systolic BP, respectively. A higher preference for terminal digits was maintained in systolic BP, although the results obtained in the practical session with the videotape showed a greater dispersion of results in diastolic BP. PMID- 2104132 TI - [Socioeconomic factors: do they influence the demand for care and the degree of satisfaction in primary care?]. AB - A survey of 248 individuals was carried out. They included both males and females aged between 16 and 80 years, and they were selected as a representative sample of the population on care in the health center "Huerta de la Reina" for an error margin of 5% and p less than 0.05. The possible influence of cultural and socioeconomic factors on the opinion of the population about the received attention and the degree of use of health care services was evaluated. 76.2% of our patients are not working, 68.5% are females and 57% are older than 46 years. These two groups show the highest rate of consultation for administrative purposes. The educational level, profession, sex, age and the district of origin do not influence the evaluation of the received care. The patients from the quarter with the lowest socioeconomic status consider that the physician pays less attention to them and have a poorer understanding of the latter's explanations (p less than 0.05). Both factors exert an influence on the evaluation of the new model of care. It was concluded that the socioeconomic characteristics of a population are very important for the development of an integrated type of attention by primary care teams. PMID- 2104133 TI - [The basic minimum set of data in primary care. A Delphi study]. AB - The term basic minimal unit of data in primary care is used for those essential data required so that all primary care professionals may carry out their work. The results of a study performed with the Delphi technique about the basic unit of data by 35 Spanish physician are reported. The results are distributed in three areas: clinical interview (12 basic data were considered), clinical history (27 essential data) and health care performance (19 minimal data). PMID- 2104134 TI - [A drug prescription study in chronic pathology at a primary care center]. AB - To evaluate the characteristics of the drug used for the therapy of chronic diseases, 1588 prescriptions from a sample of 549 continued drug prescription forms were evaluated. Every patient had a mean number of 2.9 drugs, 2.14 diagnoses and 1.41 drugs per diagnosis. The patients over 65 years had a higher number of drugs and diagnoses. A smaller number of diagnoses but a higher number of drugs per diagnoses was found for males. The drug subgroups with higher prescription rates were cardiac drugs (12.3%), diuretics (11.2%) and analgesics (9.9%). The most common diagnoses were hypertension and osteoarthritis, with 17.6% and 13.6% of prescriptions, respectively. A high rate of patients receiving vasodilators (12%) and benzodiazepines (14.7%) was found. The usefulness of the continued prescription forms for the control of chronic treatments is emphasized. PMID- 2104135 TI - [Amoxicillin/clavulanic acid and trimethoprim in the treatment of urinary infection in primary care]. AB - The effectiveness of amoxicillin/clavulanic acid (A/Cl) and trimetoprim (TMP) were compared in two different schedules: 10 days treatment and monodose, in 80 patients with, urinary tract infection (UTI) demonstrated by urine culture. The patients over 65 years, the males and those with underlying risk conditions randomly received A/Cl or TMP during 10 days. The rates of cure were 76.9% for A/Cl and 73.9% for TMP. The difference was not significant. Thirty-one patients without those features randomly received a short A/Cl course or a single dose of TMP. The rates of cure were 92.8% for A/Cl and 58.8% for TMP. The difference was statistically significant. It was concluded that, in our patients, complicated lower UTI have a similar response rate to a ten days course of A/Cl or TMP, whereas A/Cl for three days is more effective than a single TMP dose to treat noncomplicated lower UTI. PMID- 2104136 TI - [Human immunodeficiency virus infection at a primary care center]. AB - We report a descriptive study of 56 cases of HIV infection in a primary care center to evaluate its impact on the population on care, the practices at risk, the associated infections and the difficulties for control. The distribution by age, sex and practices at risk is in agreement with most series from our area. Remarkably, there is a greater rate of drug abusers and sexual promiscuity, related with the marginal type of population on care. We found a high prevalence of the most commonly associated infections, tuberculosis, syphilis and hepatitis B. This association justifies screening for these diseases and the use of the adequate prophylactic and therapeutic measures. We found important difficulties for the follow up of these patients. All these facts emphasize the need to approach this increasing health problem from the primary care setting, basically from the health education of the person with practices at risk and the overall follow-up of the involved patients. PMID- 2104137 TI - [The diagnosis and treatment of anemias in primary care]. PMID- 2104138 TI - [Imaging diagnosis. The plain-film abdomen. II]. PMID- 2104139 TI - ["And now, how many subjects do I take?" Some basic ideas on sample size (II): sample size in a problem of contrasting hypotheses with 2 samples]. PMID- 2104140 TI - [Asymptomatic bacteriuria in schoolchildren]. PMID- 2104141 TI - [Emergency referrals from a rural area]. PMID- 2104142 TI - [Gingival hyperplasia produced by nifedipine]. PMID- 2104143 TI - [An analysis of work sick leave at the Florida-Potazgo Health Center during a 1 year period]. PMID- 2104144 TI - [The preventive value of colorectal cancer screening]. PMID- 2104145 TI - [The control of hypercholesterolemia in primary care]. PMID- 2104146 TI - [Guidelines on the preparation of meetings and topics in health centers]. PMID- 2104147 TI - [Mental morbidity in a general medical practice]. AB - The present study was carried out in the city of Seville, among individuals who had attended a general practice from the Social Security. 215 subjects, aged 15 65 years, were interviewed to obtain information of the mental health status. The data were collected with the General Health Questionnaire (GHQ) and an interview for sociodemographic and health data addressing all factors which may, in general, play a role in the mental health of the individual. The prevalence of mental disorders in the study was between 42.6% and 56%. Factors such as marital status, profession, employment status, use of psychoactive drugs and stress showed significant associations with the mental health level. In the discussion, in addition to comparing our observations with those from other reports, we attempt an approach to to psychological and sociological understanding of the factors implied in mental health. PMID- 2104148 TI - [Medical residents in family and community medicine facing the problems of mental health: an opinion survey]. AB - In the present study the opinions of a group of family and community medicine residents from the Madrid Autonomous Community about the following points were evaluated: 1) The relevance that they attribute to psychiatric knowledge and skills; 2) Their degree of qualification in these areas; and 3) The use of each of these knowledges and skills in their daily clinical practice. To his end, the questionnaire elaborated by Johnson W. and Snibbe J. was used. 80.2% of the surveyed people answered the questionnaire. The results reflect the great importance that they attributed to this matter, with a priority for those more used in everyday practice and those less specialized (capacity for communicating with patients, patient-physician relationship). The usefulness of these questionnaires as a preliminary step to any educational program for family physicians is emphasized. In addition, education in mental health is considered necessary, orienting the contents of the program to the aspects more valued and used by these physicians. PMID- 2104149 TI - [The multidisciplinary health team]. PMID- 2104150 TI - [Neurological disorders: a primary care approach]. AB - The aim of this study was to evaluate the proportion of neurological disorders within the overall number of ailments treated in primary care, as well as to classify them, determine the reason for their referral to specialists, and analyze the appropriateness or justification of such referral in each case. The 553 neurological visits analyzed represented 6.1% of the total (non-bureaucratic related) number of requests for medical care. The groups cephalea/facial pain, dizziness and partial or complex seizures accounted for 60% of total. One of every three visits was referred to a neuropsychiatrist and/or hospital service. The main cause for the referral was considered clinical in only 28.3% of cases. The referral was judged inappropriate by the specialist in 13.4% of cases. The evidence that neurological disorders are not unusual, in addition to the high rate of referrals and an analysis of the reason and justification for referral, reflect the need to focus on the neurological training of non-neurologists, as well as to evaluate the appropriateness of present specialized outpatient care. PMID- 2104152 TI - [Evaluation of a clinical sign in predicting iron deficiency in women: the blue sclera]. AB - The purpose of this study was to calculate the predictive value (PV) of blue sclera (BS) in iron deficiency in women. The presence of this clinical sign was evaluated in 498 female patients at an urban primary care centre. Three observers independently evaluated the existence of BS on a scale of 0 to 3 in all female patients visited over a period of 35 weeks. Twenty eight cases of BS were detected over this period, of which 16 had ferropenia and 21 had anemia or iron deficiency. The positive predictive value of the clinical sign was 57.14%, 95% within the confidence interval of 52.77-61.51. The presence of BS was not affected by age or eye color. BS appears to be a good indicator of iron deficiency in our medium and, if confirmed by other studies, should be considered in the every-day clinical examination. PMID- 2104151 TI - [Catarrhal prodromes and pharyngotonsillar hyperemia in acute bacterial meningitis]. AB - In the pathogenesis of acute bacterial meningitis (ABM), the direct entry of the responsible microorganism at the level of the upper respiratory tract is considered as one of the most important etiopathogenic mechanisms, occasionally presenting catarrhal symptoms in the initial stages of the disease. It appears that upper respiratory tract infections favor the penetrability of certain bacteria, such as N. meningitidis and S. pneumoniae, which constitute the most frequent causes of ABM in our medium. The rhinopharynx is the most usual entry point. The present study was designed to ascertain the frequency of these prodromic signs and symptoms in ABM. The presence of this catarrhal semiology in the days prior to hospital admission was analyzed, in addition to the existence of pharyngotonsillar hyperemia (FTH) at the moment of admission of 250 cases of community-acquired ABM. We believe that these data are of clinical interest, and were not found in the reviewed series. PMID- 2104153 TI - [Results and analysis of research on HBsAg in pregnant women at a health center over 4 years]. AB - Vertical transmission of hepatitis B is the primary means of acquiring the disease by new carriers. The Cartuja Health Center performs systemic screening of pregnant women subjects as possible carriers. The purpose of the study is to determine the prevalence of pregnant carriers, seroepidemiological characteristics and intervention guidelines followed. We reviewed 454 pregnant women with serology performed between 1986 and 1989, including factors such as age, race, HBV serology, risk, and subsequent prevention. We calculated the prevalence of carriers. Moreover, we compared the proportion of Gypsy carriers versus non-carriers, and the prevalence of Gypsy versus Payos (non-Gypsy) carriers. Fourteen cases were AgBHs (+) (3.1%). There was no age difference between carriers and non-carriers. The proportion of Gypsy women in the carrier group was higher than in the non-carrier group (p less than 0.01), while the prevalence of carriers was also higher in Gypsy women than in pregnant women of Payo origin (p = 0.00082). Only one carrier had prior risk history. Of the 14 women with AgBHs (+), 13 gave birth; the recommended guidelines were followed in 9 cases. Routine screening for AgBHs in pregnant women is justified by the low sensitivity of the risk criteria, and the possibility for prevention. PMID- 2104154 TI - [Evaluation of a tuberculosis prevention and control program (1987-1989)]. AB - Tuberculosis continues to be an important health problem. A tuberculosis prevention and control program was begun in 1989 in Ciutat Badia, introducing the inclusion of those who had been in close contact with infected subjects. In the two years of the study, a total of 1,548 tuberculin tests was performed, 518 of which were positive 33%). Prevalence of tubercular infection in the study population, was 13.95%. Ages ranged from 14 to 20 years. We detected 20 cases of pulmonary tuberculosis and were able to study 91% of those who had been in close contact with the subjects in question. Three of these were detected in the latter study, and two by contact with tubercular infection. We prescribed a total of 180 chemoprophylaxes (47 primary and 133 secondary) with compliance of 60% and 71% respectively. We believe that chemoprophylaxis plays an important role in the prevention and control of tuberculosis in primary care. PMID- 2104155 TI - [Hereditary familial neuropathies: genetic counseling and early diagnosis in primary care]. AB - We present 5 cases of sensitive-motor hereditary neuropathies which were detected or controlled in primary care. Four patients had Charcot-Marie-Tooth disease (type I) and the remaining patient is a carrier of Dejerine-Sottas disease (type III). Regardless of the age of presentation of the disease, the evolution has been slow but steady in all cases. Talipes cavus is the most frequent secondary deformity. An electroneuromyographic study and a neural biopsy were the complementary diagnostic tests used. Three of the patients presented family antecedents. We believe that early diagnosis, family study and genetic advice are of great importance in primary care. PMID- 2104156 TI - [Adenopathies]. PMID- 2104157 TI - [Methods of investigation: bibliography with comments (I)]. PMID- 2104158 TI - [The detection and treatment of severe chronic respiratory insufficiency in primary care]. PMID- 2104159 TI - [The antibiotic prescription in primary care]. PMID- 2104160 TI - [The effectiveness of the personalized letter for increasing the coverage of influenza vaccination]. PMID- 2104161 TI - [A nursery for the children of fair workers. The first experience in Cordoba]. PMID- 2104162 TI - [Fetal distress in prolonged pregnancy]. PMID- 2104163 TI - [Poorly defined signs and symptoms or community geriatric syndromes?]. PMID- 2104164 TI - [Emergencies in primary care and the referral of patients to the hospital]. PMID- 2104165 TI - [Bilateral galactorrhea in chemoprophylactic treatment with isoniazid]. PMID- 2104166 TI - [Report of a case of familial Mediterranean fever]. PMID- 2104167 TI - [Intervention programs in ischemic cardiopathy from the primary health care viewpoint]. PMID- 2104168 TI - [Cardiovascular risk factors. An audit of their detection in primary care]. AB - After having found that the prevalences of hypertension, hypercholesterolemia, obesity and smoking were low in our adult population on care, we developed a study to investigate the causes of the problem and to introduce measures for its solution following the methodology of the medical audit. The indexes showed that the performance of preventive cardiovascular activities (PCVA) was low: blood pressure measurement 45%, blood cholesterol determination 23%, height and weight measurement 8% and questioning on smoking habits 40%. After the implementation of corrective measures, indexes of 79%, 76%, 71% and 56%, respectively, have been achieved. In addition, a defective recording of the detected risk factors was found: 87% in the clinical history record, 72% in the age and sex card; after the corrective measures, the rates were 98% and 91% respectively. The present study demonstrates the effectiveness of quality control measures carried out by the professionals responsible for care to improve its quality. PMID- 2104169 TI - [Ischemic cardiopathy in primary care. A descriptive study]. AB - A descriptive study of ischemic heart disease in a primary care center is reported. From the recording systems 112 patients with IHD (9 of them dead) were identified. The calculated incidence and prevalence rates were 1.9/1000 and 10.9/1000, respectively. There were remarkably high rates of cardiovascular risk factors. The most common forms of presentation were myocardial infarction in males and angina in females. The physicians of the primary care center played a role in the diagnosis in 17% of patients. In addition, the disease was exclusively managed in the primary care center in 29% of patients, most of them over 65 years of age. The role of the primary care physician in the diagnosis and control of this condition is emphasized. PMID- 2104170 TI - [An evaluation of the Reflotron portable analyzer for cholesterol determination in primary care]. AB - We have evaluated serum cholesterol in a primary care center with a recently introduced portable analyzer: Reflotron (Boehringer Mannheim). The linearity and exactitude were investigated with Hitachi 704 (Boehringer Mannheim) used in the reference laboratory. Accuracy was also tested. We found a good accuracy after repeated analysis (n = 30) of two control sera with a variation coefficient of 2.77% in the first (mean = 125.14 mg/dl, SD 3.47) and 2.94% (mean = 254.53 mg/dl, SD 7.49) in the second. We found an overall lack of accuracy of Reflotron with a more pronounced negative bias in capillary blood (mean d = 30.93 mg/dl, dSE 3.25) than in serum (mean d = dSE 1.12). We found a positive linear correlation both using serum (r = 0.9845; n = 45) and capillary blood (r = 0.9094; n = 30). We feel that Reflotron is useful for primary care due to its good accuracy and linearity regarding the reference method, but its inexactitud should be taken into account. We emphasize the need for quality control to investigate its limitations when the results are analyzed. PMID- 2104171 TI - [Acute myocardial infarct: the problems after discharge in primary care]. AB - The patients with acute myocardial infarction raise important problems to the primary health care professionals after hospital discharge. We report six patients covering a wide range of problems related with their control ant therapy: from the asymptomatic infarction discovered during a blood pressure control to patients with cardiac failure, postinfarction angina and arrhythmias. Psychosocial problems are also considered. There is a need to encourage secondary prevention activities in these patients, suppressing and/or controlling the existing risk factors. PMID- 2104172 TI - [A consensus accord for the control of cholesterolemia in Spain. Madrid. March 1989]. PMID- 2104173 TI - [Imaging diagnosis. Acute myocardial infarct]. PMID- 2104174 TI - [Risk factors of coronary disease]. PMID- 2104175 TI - [The role of primary care in the follow-up of ischemic cardiopathy]. PMID- 2104176 TI - Induction of humoral manifestations of autoimmunity following intraperitoneal injection of complete Freund's adjuvant in mice. AB - Several animal models of arthritis are produced using complete Freund's adjuvant (CFA) alone or with collagen as an arthritogen. Successful induction of arthritis is reported to require that the adjuvant mixture be administered by intradermal or subcutaneous routes. The resulting arthritis is caused by primarily cellular immune responses. Data presented in this paper show that giving CFA by intraperitoneal (I.P.) inoculation results in a humoral autoimmune response, with no obvious signs of arthritis. This humoral autoimmune response is characterized by production of autoantibodies to nuclear and cytoplasmic antigens, elevated levels of circulating immune complexes, and in approximately 25% of mice, rheumatoid factor. PMID- 2104177 TI - Immunological abnormalities in a group of patients with limited cutaneous systemic sclerosis and prominent vascular disease. AB - Antinuclear antibodies, circulating immune complexes, rheumatoid factors and anticardiolipin antibodies were detected in the sera of 17 patients affected by the limited cutaneous subset of systemic sclerosis and marked clinical evidence of ischaemic cutaneous lesions (fingertip ulcerations). This study was designed to evaluate the possible role of anticardiolipin (aCL) antibodies and other immunological disorders in the endothelial damage characteristic of the disease. ACL antibodies were found in 41% of the patients. With the exception of a significant connection with positive rheumatoid factor tests (RIA), no notable associations between anticardiolipin antibodies and antinuclear antibodies, circulating immune complexes (CIC), and other serological abnormalities were found. ACL antibodies did not significantly correlate with the presence of vascular lesions in our patients. However, a role of these antibodies in endothelial damage cannot be excluded, possibly in association with other serum factors such as immune complexes and antinuclear antibodies. A positive connection between the incidence of CIC and the severity of lung perfusion impairment was observed, and the previously reported relationship between anticentromere antibodies and calcinosis was indirectly confirmed. PMID- 2104178 TI - The LY-1 gene expression in murine hybridomas producing autoantibodies. AB - Studies presented here demonstrate the expression of the Ly-1 gene and the detection of the Ly-1 cytodifferentiation antigen in murine hybridomas producing autoantibodies. We examined the transcription of the Ly-1 gene in thymocytes and 140 hybridomas producing autoantibodies of various specificities which were obtained from normal and autoimmune disease prone mouse strains. As previously demonstrated thymocytes stain brightly for Ly-1 by immunofluorescence and express Ly-1 transcripts. In our panel of hybridomas producing autoantibodies Ly-1 transcripts were detected in 31 (45%) out of 69 NZB hybridomas and 7 (88%) out of 8 viable motheaten hybridomas. S1 nuclease protection experiments showed that Ly 1 transcripts detected in thymocytes and B cells are the product of the same gene. The B cell transcripts are functional since immunofluorescence and Western data presented here detected the Ly-1 protein in hybridomas cells which were found to transcribe the Ly-1 gene. Interestingly a polymorphic transcription of the Ly-1 gene was observed in B cells and B cell hybridomas as compared to thymocytes. Our results obtained in the hybridoma system firmly establish a major contribution of the Ly-1 B cell subset to the production of DNA specific autoantibodies and a smaller contribution to the production of rheumatoid factors and "natural", multispecific autoantibodies. PMID- 2104179 TI - Autoimmunity in nephritis. PMID- 2104180 TI - Distinct surface phenotypes of B cells responsible for spontaneous production of IgM and IgG anti-DNA antibodies in autoimmune-prone NZB x NZW F1 mice. AB - Autoimmune-prone NZB x NZW F1 (B/W F1) mice produce a high titer of anti-DNA antibodies, In vivo and in vitro studies showed that in the early life of these mice, the immunoglobulin isotype of these antibodies almost exclusively belongs to IgM class, however, IgG anti-DNA antibodies begin to develop when the mice are about 5-6 months old and the titer exceeds that of IgM antibodies from age 7 months on. We asked whether or not the B cell population responsible for IgM and IgG antibody production belongs to the same lineage. The surface phenotypes of B cell populations responsible for the spontaneous production of either IgM or IgG anti-DNA antibodies were examined using panning and sorting methods with several monoclonal antibodies to B cells, including CD5 (Ly-1) and Lp-3; the latter defines a unique B cell differentiation antigen. We obtained evidence that surface phenotypes of B cells secreting IgM anti-DNA antibodies belong to CD5+ Lp 3- and those of B cells secreting IgG anti-DNA antibodies which occur only in old B/W F1 mice belong to CD5- Lp-3+ subpopulations. The majority of peritoneal B cells were CD5+ Lp-3+ throughout the life span of the mice and anti-DNA antibody production was never evidenced. These findings were discussed in relation to age associated changes of B cell populations in the spleen of this strain of mice. PMID- 2104181 TI - Soluble interleukin-2 receptors and autoantibodies in the serum of healthy elderly individuals. AB - Recently, we reported an increased incidence of various autoantibodies in a healthy elderly population (Group A, 64 subjects). Presently we examined whether there is variability in the expression of the age-associated immunological aberrations between different geriatric populations by extending our observations in another healthy elderly population (Group B, 119 subjects). We also determined the serum levels of soluble IL-2 receptors (sIL-2R) attempting to define the activation status of the immune system during senescence. Compared to non-elderly controls, healthy elderly individuals exhibited a significantly higher incidence of autoantibodies as well as significantly higher levels of sIL-2R in serum (p less than 0.001), the latter possibly suggesting the occurrence of lymphocytic activation during the ageing process. The overall prevalence of autoantibodies was statistically associated with the presence of raised sIL-2R levels in serum (p less than 0.005). These aberrant immunological phenomena were more frequent among the elderly of group A, compared to group B (p less than 0.005). In contrast to the uniform expression of various autoantibodies previously observed in group A, the autoantibody profile of group B consisted mainly of rheumatoid factor and antibodies to single-stranded DNA. Finally, no association could be demonstrated between the presence of autoantibodies and HLA antigens in 42 elderly studied. PMID- 2104182 TI - Aberrant lymphocyte migration patterns in systemic lupus erythematosus (MRL/l, MRL/n) mice are independent of the micro-environment. AB - Mice with systemic lupus erythematosus (SLE) have unusual patterns of lymphocyte traffic characterised by diminished uptake of intravenously injected autoimmune cells into lymph nodes. This study examines the influence of the lymphocyte micro environment on this aberrant migratory behaviour. To evaluate lymph node lymphocyte-endothelial interactions which can affect lymphocyte distribution without the in vivo influence of liver and spleen, the in vitro high endothelial venule (HEV) binding assay was used. Lymph node HEV binding of autoimmune MRL lpr/lpr (MRL/l) and MRL(-)+/+ (MRL/n) lymphocytes was increased when compared with CBA/T6 lymphocytes and contrasted with diminished lymph node uptake noted in vivo. This was independent of the lymph node source (MRL/l, MRL/n, CBA/T6) onto which the lymphocytes were overlaid. To examine the influence of the microenvironment on in vivo traffic, 21Cr-labelled lymph node cells from normal CBA/T6 mice were injected into sex-matched MRL/l, MRL/n and CBA/T6 recipients. The distribution of cells was the same in each recipient strain suggesting that the micro-environment had little influence on the lymphocyte trafficking profiles of autoimmune mice. This study supports the view that aberrant lymphocyte migration in autoimmune mice results from defects intrinsic to the lymphocyte population and not the micro-environment. PMID- 2104183 TI - Induction of diabetes in PVG/c strain rats by manipulation of the immune system. AB - A combination of thymectomy and sublethal irradiation (Tx-X) consistently induced diabetes in female rats of the PVG/c strain. The incidence of diabetes varied from 10.7% to 53.4% in seven successive Tx-X groups (mean 29.7%). Both clinical and subclinical disease was observed with the majority of affected animals developing the former condition. This was acute in onset, rapidly fatal (1-4 days) and characterized by ketosis and lipidemia. Overtly diabetic rats had markedly raised plasma glucose concentrations compared to normal rats of the same strain and plasma immunoreactive insulin concentrations were correspondingly depressed in this group. Histopathological change within the islets of Langerhans correlated with clinical status and ranged from diffuse atrophy in the majority of the acutely diabetic rats to mild and focal lymphocytic insulitis in a proportion of the non-diabetic rats. Islet cell autoantibodies were demonstrated by indirect immunofluorescence in approximately 25% of clinically diabetic animals. The majority of diabetic rats were found to be responsive to insulin and the clinical signs could be reversed by daily parenteral insulin administration. These observations implicate the immune system in diabetes generation and are consistent with an immune mediated pathogenesis as the underlying cause of the islet cell destruction. This syndrome may thus be a potentially useful animal model for type 1 (insulin dependent) diabetes in man. PMID- 2104184 TI - Autoimmune angioedema: a new role for autoantibody in disease pathogenesis. AB - Angioedema may be due to hereditary forms of Cl-Inh deficiency, but recently an autoimmune form of angioedema has been described in which the mechanism is novel. While the peripheral blood monocytes of patients with autoimmune angioedema produce a normal, functionally active, 105 KD Cl-Inh in normal quantities, the Cl Inh isolated from the patient's plasma exists in a dysfunctional lower molecular weight (96 KD) performance. Rather than bind and biologically inactivate the enzyme, a relatively common phenomenon in autoimmune disease, the autoimmune angioedema cleave the Cl-Inh molecule. The following sequence of events is proposed: structural and functionally normal Cl-Inh is synthesised and secreted, this secreted inhibitor is complexed by autoantibody and following enzyme interaction, denatured 96 KD Cl-Inh is proposed. This process depletes the pool of normal, functional Cl-Inh to critical levels and predisposes patients to episodes of oedema. PMID- 2104185 TI - Soluble interleukin-2 receptor secretion defect in vitro in HLA-B8, DR3 positive subjects. AB - Several studies have shown that HLA-B8,DR3 positive subjects may display T cell dysfunctions. Recently, a soluble form of the receptor for IL-2 (sIL-2R) has been demonstrated in human sera and in vitro-stimulated culture supernatant from human T lymphocytes. In the present paper we report sIL-2R serum levels and sIL-2R production from peripheral blood mononuclear cells in HLA-B8,DR3 positive subjects. We found that HLA-B8,DR3 positive subjects have the highest values of serum sIL-2R, but comparing the values of these subjects with those of negative ones no significant difference was observed. As regards the in vitro production of sIL-2R, no difference exists for unstimulated cultures, whereas after stimulation, the HLA-B8,DR3 positive subjects showed the lowest values compared with negative ones. It is noteworthy that these changes are observed in autoimmune diseases linked to this HLA phenotype. PMID- 2104186 TI - Increased interleukin 2 receptor expression in post-gestational women: relationship to impaired glucose tolerance and islet cell antibodies in pregnancy. AB - Fifteen women with positive islet cell antibodies were identified in a group of 115 consecutive patients found to have impaired glucose tolerance in pregnancy. These subjects were postulated to be at increased risk of later developing type 1 diabetes mellitus. They were examined post--partum for HLA types known to be associated with this disease and for any increase in Interleukin 2 receptor expression or alteration of T cell subsets of possible relevance to its pathogenesis. Fifteen women negative for islet antibodies and with normal glucose tolerance during previous pregnancy and 15 women with a normal fasting plasma glucose who had never been pregnant were studied as controls. Using flow cytometric techniques a significant increase in both the number and proportion of activated (Interleukin 2 receptor, CD25) lymphocytes in the peripheral blood of women who had islet cell antibodies and previous impaired glucose tolerance in pregnancy was found (0.14 +/- SE 0.03 x 10(9)/l; 7.1 +/- 1.1%) when compared with normal parous controls (0.09 +/- 0.01 x 10(9)/l; 4.2 +/- 0.6%), p less than 0.01 x 10(9)/l; showed significant increases when compared with nulliparous controls (0.04 +/- 0.01 x 10(9)/l; 2.1 +/- 0.2%), p less than 0.01. No differences were detected between the three groups with respect to total T-lymphocytes (CD3), helper T-lymphocytes (CD4), suppressor cytotoxic T-lymphocytes (CD8), or the inducer of suppressor (Leu 3+/Leu 8+) subset of T-lymphocytes. Three women persistently islet cell antibody positive, two of whom were HLA DR4, showed impaired glucose tolerance at the time of lymphocyte subset analysis, while two further patients, one DR3 and the other DR4, had developed type 1 (insulin dependent) diabetes. No correlation between increased Interleukin 2 receptor expression and glucose intolerance was demonstrated. We conclude that islet cell antibody positive women with impaired glucose tolerance during pregnancy are at increased risk of later developing type 1 diabetes but that heightened immune activation present in these women is in part a post-pregnancy phenomenon. PMID- 2104188 TI - Analysis of the autoimmune response in lupus mice: the behaviour and lifespan of anti-DNA-secreting B-cell clones. AB - We present the results of a study of the physical, haematological and serological features of the progress of the SLE-like syndrome in MRL/Mp-lpr/lpr and (NZB x NZW)Fl mice. As part of this study, we have analysed the IEF spectrotypes of anti ssDNA antibodies in the sera of these mice and shown that the anti-ssDNA response is clonally restricted, as we have previously shown in a mouse chimaera model and in human SLE. Sequential qualitative and quantitative analysis of anti-ssDNA clonotypes has revealed that the lupus mouse anti-ssDNA clones are relatively short lived, having a lifespan of only 6 to 8 weeks, contrasting sharply with the much longer lifespan previously reported for a mouse anti-DNP-secreting clone and the exceptionally long lifespan of most anti-ssDNA-secreting clones of SLE patients. The implications of these observations for our understanding of the regulation of the autoimmune response are discussed. PMID- 2104187 TI - Sequence analysis of monoclonal antibodies derived from a patient with idiopathic thrombocytopenic purpura. AB - Autoantibodies directed at the platelet membrane glycoprotein Ib (GPIb) can mediate a severe form of idiopathic thrombocytopenic purpura (ITP). The platelet specific antibody from plasma of one patient (DM) with this form of ITP displays a public idiotype termed DMId. The DMId idiotype has been found in the plasma of several patients with ITP, usually in association with GPIb-specific autoantibodies. As a step in the understanding of the molecular genetics of this form of ITP we have determined the nucleotide sequences of expressed V region genes selected from a panel of five human lymphoblastoid cell lines derived from patient DM. Two of the lines secreted antibodies that bound GPIb, and three of the lines secreted antibodies that expressed DMId. The H chain sequences of the DMId-positive antibodies and of one of the GPIb-binding antibodies belong to the VH4 family. The second GPIb-binding antibody belongs to the VH1 family. All have multiple substitutions from previously published sequences giving these antibodies the appearance of having been antigen driven. These results are consistent with the hypothesis that autoantibodies in ITP arise from a "normal" immune response inappropriately directed at platelet antigens. Further, our results suggest that VH4 gene segments may be recruited preferentially into the DMId-positive, GPIb-specific autoantibody response. PMID- 2104189 TI - Cytokines in the pathophysiology of systemic lupus erythematosus. PMID- 2104190 TI - The complex role of epithelial cell MHC class II antigen expression in autoimmune endocrine disease. PMID- 2104191 TI - Effects of inosine and adenine on nucleotide levels in the post-ischemic rat heart, perfused with and without pyruvate. AB - Reports on enhanced nucleotide regeneration by purines during reperfusion are conflicting. We have, therefore, evaluated the effects of inosine or adenine, administered after ischemia, on adenine nucleotide levels and function in isolated rat hearts. The hearts were perfused with a Tyrode solution, containing 10 mM D-glucose, with or without 5 mM pyruvate. After 15 minutes without flow, the hearts were reperfused for 45 minutes with 20 microM purine and 0.5 mM D ribose. Adenine nucleotide levels tended to recover better in the purine-treated groups. The purines decreased the ATP/ADP ratio by 10-15% (p less than 0.05) if pyruvate was absent. The IMP level in the inosine/glucose group exceeded that in all other groups by a factor of two (p less than 0.001). Inosine increased the adenosine concentration in the effluent sixfold (p less than 0.005). The hypoxanthine concentration rose up to four times following adenine treatment (p less than 0.05). The administration of purine, with or without pyruvate, did not affect mechanical recovery, heart rate or coronary flow. We conclude that inosine and adenine failed to improve cardiac function and hardly affected nucleotide levels in the reperfused heart. PMID- 2104192 TI - The effect of distension of the urinary bladder on left ventricular inotropic state in anesthetized dogs. AB - To decide whether distension of the urinary bladder reflexly affects the left ventricular inotropic state, experiments were performed in eight dogs anesthetized with pentobarbitone. After cannulation of both ureters the urinary bladder was repeatedly distended through a urethral catheter with warm Ringer solution at a steady intravesical pressure. The maximal rate of rise of left ventricular pressure (dP/dtmax) obtained at constant heart rate and cardiovascular pressures was used to assess changes in left ventricular inotropic state. Arterial blood pressure was prevented from changing by a pressurized reservoir containing warm Ringer solution and connected to the femoral arteries. Following prevention of the reflex increase in heart rate by atrial pacing, distension of the urinary bladder always increased the maximal rate of rise of left ventricular pressure in the eight dogs. There were no significant changes in left ventricular systolic or end-diastolic pressures. The increase in maximal rate of rise of left ventricular pressure was abolished following the administration of propranolol. The results indicate that a reflex increase in left ventricular inotropic state occurred in response to distension of the urinary bladder. This reflex response involved beta-adrenergic stimulation. PMID- 2104193 TI - Influence of age on oxidative damage in mitochondria of ischemic and reperfused rat hearts. AB - Hearts from rats aged 3 months and 24 months respectively were isolated and subjected to a brief ischemia. The extent of myocardial injury, measured by release of creatine phosphokinase into coronary effluents and by developed tension, was greater in the young rats than in the old when compared with their corresponding non-ischemic controls. The amount of peroxidation, measured in the isolated mitochondria using the malondialdehyde method, was also greater in the younger rats. In contrast, when mitochondria from non-ischemic hearts were incubated for 20 minutes in a medium containing FeCl3, NADPH and ADP, known to generate hydroxyl radicals, significant peroxidation (together with a decrease in respiratory control indices) was obtained only from mitochondria isolated from the older rats. If, as the in vitro results suggest, the mitochondria of the old rats are not less sensitive to peroxidative attack, the difference between the effects of ischemia in the two age groups may be due to a lower rate of formation of reactive species of oxygen or to a greater anti-oxidative cytosolic capacity in the hearts of older rats. Alternatively, the overall oxidative stress following ischemia may be due to the effects of different radicals which target different parts of the mitochondrial membrane. PMID- 2104194 TI - Delayed protection by 7-oxo-PGI2 against cardiac transmembrane ion shifts and early morphological changes due to ischemia and reperfusion. AB - In previous experiments on dogs subjected to local myocardial ischemia, we have shown a late and prolonged anti-ischemic and anti-arrhythmic effect of a single injection of the stable prostacyclin analogue, 7-oxo-PgI2. The protection was dependent on dose and time. Maximal effects were observed 48 hours after an optimal intramuscular dose of 50/micrograms/kg. To study the mechanism of this protective effect we have followed the time-dependent changes in transmembrane cation homeostasis induced by ischemia and reperfusion by measuring the intracellular potassium, sodium and calcium ion concentrations in Langendorff guinea pig heart preparations isolated from untreated control animals and from animals receiving a single intramuscular injection of 50/micrograms/kg 7-oxo-PgI2 48 hours before preparation. Global ischemia was produced by stopping perfusion for 25 minutes and was followed by reperfusion. In a second series, similarly treated and untreated hearts were fixed for electron microscopy after 25 minutes' global ischemia as well as after 15 minutes' reperfusion. Ischemia and reperfusion evoked a rapid loss of intracellular potassium and gain of sodium as well as an accumulation of calcium in the reperfusion phase. Pretreatment with 7 oxo-PgI2 prevented all these changes. It also prevented the shortening of the sarcomers and swelling of mitochondria induced by ischemia and the deposition of calcium-dense granules in mitochondria appearing after reperfusion. The findings support the hypothesis that 7-oxo-PgI2 has a delayed cytoprotective action which preserves normal transmembrane ion transport and normal structure of myocardial cells under conditions of ischemic and reperfusion injury. PMID- 2104195 TI - Transport and action of spermine in rat heart mitochondria. AB - At concentrations of 0.5-1.0 mM, spermine fully prevents the fall of membrane potential induced in rat heart mitochondria either by aging at room temperature or by the addition of palmitoyl CoA. Spermine also prevents the inhibitory action of palmitoyl CoA on adenylate translocase activity. When added to heart mitochondria de-energized by the same damaging conditions (aging or addition of palmitoyl CoA) spermine restores both membrane potential (provided that ATP is also added) and the activity of adenylate translocase. A part of added spermine is immediately bound to anionic sites on mitochondrial membranes, another part is slowly transported into heart mitochondria. Whereas binding is an energy independent process, transport is driven by the transmembrane potential. Spermine penetrates the mitochondrial matrix at significant rates only at high membrane potential, such as that produced either by phosphate transport or addition of nigericin. PMID- 2104196 TI - The effect of swimming exercise on spontaneous ventricular defibrillation and ventricular fibrillation threshold in the isolated perfused rat heart. AB - Effects of swimming exercise training on left ventricular contraction and relaxation, the incidence of spontaneous defibrillation and the ventricular fibrillation threshold were studied in the isolated, perfused rat heart. The heart/body weight ratio was 4.8 +/- 0.4 x 10(-3) in swimmers compared with 3.9 +/ 0.6 x 10(-3) in sedentary controls (p less than 0.0005). The spontaneous heart rate was lower in isolated hearts of trained animals (222 +/- 18 bpm compared with 244 +/- 28, p less than 0.05). Left ventricular systolic pressure was higher in trained hearts and the rate of ventricular relaxation enhanced (p less than 0.05). The ventricular fibrillation threshold was 7.2 +/- 5.2 and 10.8 +/- 6.1 mamp in hearts of swimmers and controls, respectively, the difference not being significant. The incidence of spontaneous defibrillation was not significantly different between the two groups. It is concluded that, while swimming induces cardiac hypertrophy and hemodynamic changes, it neither protects against the induction of ventricular fibrillation nor facilitates spontaneous defibrillation in the isolated, non-ischemic rat heart. PMID- 2104197 TI - A rapid and efficient procedure for transformation of Saccharomyces cerevisiae intact cells with plasmid DNA. AB - A rapid and efficient yeast transformation procedure has been developed through investigation of factors affecting transformation efficiency. The manipulation of the entire procedure can be done within one and one half hours. High yield of transformants is obtained by: adding calf thymus DNA as carrier DNA; adding PEG4000, carrier DNA and plasmid DNA to cell suspension simultaneously; prolonging heat shock at 42 degrees C from 5 min to 25 min and spreading the transformation mixture directly onto agar plates after heat shock. The pretreatment of yeast intact cells with LiAc can be omitted in this procedure. The transformation rates of four types of plasmid DNA were as follows: pCN60: 3.5 7.2 x 10(4) (for linear pCN60/BamHI: 1.6 x 10(5)); YEp13: 1.7-2.6 x 10(4) (for linear YEp13/BamHI: 8.0 x 10(4)); RC4: 3.7 x 10(4); YIp5/StuI: 7.6 x 10(3). Seven recipient strains transformed by using this procedure all reached the yields of over 10(4) transformants per microgramme of DNA. PMID- 2104198 TI - Molecular cloning of 5'-regulatory region of bovine alpha S1-casein gene. AB - A DNA fragment of bovine alpha S1-casein gene was obtained from bovine genomic library using bovine alpha S1-casein cDNA as a probe. Restriction endonuclease map and Southern blot analysis suggest that it contains the complete 5' regulatory region of bovine alpha S1-casein gene. PMID- 2104199 TI - Plant regeneration from protoplasts of a super Chinese rice (Oryza sativa L.) cultivar--Zhonghua NO.8. AB - Green rice plants were regenerated from protoplasts, which were derived from cell suspension of Oryza sativa L. cut. Zhonghua No. 8, a super Chinese rice cultivar with high productivity, good quality and high resistance to both bacterial blight and blast. The embryogenic calli were initiated from mature embroys. It took about 4 months to establish the cell suspenion. The regeneration plants from protoplasts were obtained in 2 months after the isolation of protoplasts. PMID- 2104200 TI - High frequency plant regeneration from protoplasts of wheat. AB - Calli were initiated from the mature seeds of wheat (Triticum asetivum L.cv. Xuzhou 211), and suspension cultures were established. The protoplasts isolated from suspension cells were cultured in the modified MS medium solidified with 0.8% agarose. Regenerated cells divided and calli formed. Whole plants were regenerated from protoplast-derived calli. Colony formation was promoted when the medium with lower osmotic pressure was added after two weeks culture. The frequency of regenerated plants was increased with lower concentration of sucrose in the differentiation medium. Shoots were induced effectively with high concentration of cytokinins and calliferous shoots were avoided. The frequency of regenerated plants was affected when protoplast-derived calli were transferred onto the differentiation medium in different periods. PMID- 2104201 TI - Plant regeneration from Ri T-DNA transformed roots of cabbage. AB - Ri T-DNA transformed roots were induced out on hypocotyl segments of cabbage infected with Agrobacterium rhizogenes. After cultured for four months on solid MS medium without hormones, some parts of a few of transformed roots were dedifferentiated into callus clumps, and then redifferentiated into shoot buds. On solid MS medium supplemented with kinetin, shoot buds were differentiated directly from transformed roots without callus formation. Among several concentrations of kinetin, 14 microM gave rise to the best results for differentiation of shoot buds. In liquid MS medium, 4.5 microM of 6 benzylaminopurine (BA) also showed the increase in the number of shoot buds from transformed roots. All of these shoot buds were able to grow further, root out on root induction medium, and develop into young plants. PMID- 2104202 TI - Interspecific protoplast fusion in Streptomyces--selection of thermotolerant antibiotic-producing recombinant. AB - The thermotolerant fusants were obtained after interspecific protoplast fusion between S. qingfengmyceticus M15S (SMr, stop growth at 39 degrees C, producing qingfingmycin with wide antimicrobial spectrum) and S. hygroscopicus var. jinggangensis *75 (SMs, grow well at 42 degrees C, producing jingganmycin of antifungus) by directly selecting from the regeneration plates containing SM 100 micrograms/ml and incubated at 42 degrees C. The fusion frequency was about 10( 5) -10(-4). The stable thermotolerant recombinants with antimicrobial activity were obtained. The properties of their products were quite different from that of the parents (Qm, Jm). The antimicrobial substance produced by recombinant F6-6 consists of two components: one has acid-alkaline indicator property; the other is fluorescent under UV light. The antimicrobial products of F1-16, F1-38 and FM3 32 have absorption peaks at 274nm, which suggests that a cytosine moiety may be present in their molecules. PMID- 2104203 TI - Research and application of enzyme FET sensitive to penicillin. AB - Enzyme FET (Field effect transister) is a kind of new device developed recently, which is made through the combination of semiconductor and biological technology. Enzyme FET with differential output can provide automatic compensation for some external factors, e.g. variations of temperature and pH in bulk solution. By using differential measurement, drift of the output voltage with decreased time, and the sensor being miniaturized through the use of "pseudo-reference electrode". Differential model penicillin-ENFET was constructed by modifying one of the dual ISFET gate with a membrane of cross-linked bovine serum albumin (BSA) penicillinase and the other with a membrane of cross-linked BSA. It responded linearly to penicillin in 0.01M and 0.02M phosphate buffer with sensitivities of 6.5-7.0mV/mM and 3.2-3.6mV/mM over the concentration ranges of 0.5-14mM and 0.5 25mM, respectively. When immersed in 0.01M phosphate buffer and stored in 4 degrees C, this detector had a life time of over 6 months with only a slight decline of output. Accumulative total usage times of the detector could be over one thousand. Finally, the practical applications of differential model penicillin-ENFET in assaying penicillin concentration of fermentation broth are concerned. PMID- 2104204 TI - Cloning of the bacteriophage T7 lysozyme gene. AB - Plasmid pBR322 and its derivative containing strong promoter phi 10 of bacteriophage T7 RNA polymerase were used as vectors. A fragment of bacteriophage T7 DNA which was digested with two restriction endonucleases (AvaII and HaeIII) was cloned in the BamHI site of plasmid pBR322 and its derivative pAR951, respectively. The inserted DNA is a segment of 632 base pairs containing the complete coding sequence of both T7 gene 3.5 and weak promoter phi 3.8 for bacteriophage T7 RNA polymerase. The function of T7 gene 3.5 is known to code for bacteriophage T7 lysozyme. Transformants that carry the recombinant plasmid were tested for intracellular lysozyme by adding CHCl3. Both cloned strains produce active T7 lysozyme. The gene product, T7 3.5 protein, was analyzed by 10 -20% gradient polyacrylamide- SDS electrophoresis. The result showed that the expression of inserted T7 gene 3.5 in pBR322 derivative is stronger than that in pBR322. PMID- 2104205 TI - Technology of the divalent engineered diarrhea vaccine (K88, K99) production by high cell density fermentation and the antigen overexpression. AB - This paper describes the production of divalent K88, K99 antigens by high cell density fermentation and gene overexpression. The cell density reached above 40 at A600nm and the antigens were at 2(12) level. The thousands dosage of the vaccine can be made by using 10 I broth of the fermentation. The stability of the plasmid showed that about 30 percent of the bacteria lost its plasmid after 20 h fermentation. It was found that the antigens were overexpressed and located in both the pili of E. coli and in the medium in equal quantities. It means that the expression and regulation of the genes of K88, K99 may be different from the wild type of enterotoxingenic E. coli. A large number of the vaccinated pregnant sow showed that the piglets were effectively protected from the infection of enterotoxingenic E. coli. The results indicated that the large quantities requirement of the vaccine could be provided by using a small fermenter. This vaccine consists of two forms of the antigen K88, K99 which, when present in the pili as well as the medium, is more favorable to stimulate the production of antibody in the colostrum of pregnant sow. PMID- 2104206 TI - High expression of tumor necrosis factor alpha cDNA in E. coli using site specific deletion mutagenesis. AB - Using oligonucleotide-directed site specific mutagenesis technique, a TNF-alpha cDNA coding 157 amino acids without signal sequence and initiated with ATG was obtained. Sequencing data showed the precise deletion and insertion of the DNA fragment as designed. The modified TNF gene was expressed in E. coli with a expression vector pBV220. The expression level reached 10(8) units per liter culture. The scanning of the SDS-PAGE gel showed that the amount of the expressed TNF is about 22.8% of total soluble bacterial protein. The TNF activity can be neutralized with TNF monoclonal antibody. PMID- 2104207 TI - Molecular cloning of a DNA segment essential for replication from Streptomyces hygroscopicus strain 10-22 and localization of its minimal functional region. AB - The 13 kb DNA segment responsible for replication has been isolated from Streptomyces hygroscopicus subsp. yingchengensis strain 10-22 using a pBR322 derived Streptomyces replication-probe vector pIJ2703. The restriction map of the hybrid plasmid, pHZ54, has been constructed. Following a series of deletion and subcloning experiments, the minimal functional region for replication was located within a 2.86 kb DNA fragment. Subsequently, this region was further shortened into a 2 kb region by exonuclease III deletion. A few small bifunctional plasmids able to replicate in E. coli as well as in Streptomyces, were obtained during the above process. Some plasmids could be used as shuttle vectors. PMID- 2104208 TI - Cloning and expression of mosquito larvicidal protein gene from a highly toxic local strain of Bacillus sphaericus. AB - Bacillus sphaericus strain 10 (BS10), isolated from Jiangsu Province of China, is highly toxic to the mosquito larvae. During sporulation, BS10 produces a parasporal crystalline protein which is toxic to the larvae of a number of mosquito species, and extremely toxic against the larvae of Culex pipiens. Using the Escherichia coli cloning vector pAT153, two clones which hybridized with the synthesizing 18-bases oligonucleotides probe have been obtained. One of the recombinants, TG1 (pFL37), contains a 4.0 kb HindIII DNA fragment from BS10, and produces the 43 kd larvicidal toxin protein. Western blotting analysis and biological assay of mosquito larvicidal activity confirm that larvicidal toxin gene of BS10 is expressed in E. coli. PMID- 2104209 TI - The study on transgenic mice. AB - The structural gene coding for human growth hormone (hGH) was fused to the promoter of the mouse gene for metallothionein-1. These fusion genes were introduced into pronuclei of the fertilized eggs of mice by micro-injection. We have injected MT-hGH genes into 121 mouse eggs which were transferred into the oviducts of eleven pseudo-mothers. Seven out of eleven mothers gave birth. Forty three litters were born. These litters were grown-up and their tails were cut for isolating the DNA. The DNA of each mouse was examined by dot hybridization and Southern blotting. We found that eighteen mice had incorporated the fusion genes and grew larger than control mice. Synthesis of human growth hormone was induced further by zinc, which normally induces metallothionein gene expression. We also isolated the RNA from the livers of transgenic mice. The RNA was hybridized with hGH gene. It showed that on the transcription level the hGH gene was transcribed into mRNA in the transgenic mice. Using the same method to examine the second and third generation of the transgenic mice, we found that the incorporated gene could be inherited for generations. But the body-weight of transgenic mice appeared to decrease in the progeny. The offspring obtained from different combinations of parents (carrying or not carrying hGH gene) were different. PMID- 2104210 TI - Immobilization of callus tissue cells of Salvia miltiorrhiza and the characteristics of their products. AB - The Salvia miltiorrhiza callus tissue cells were entrapped with 3% alginate. The immobilized cells were incubated in medium with LS + KT 0.1 + NAA 1.0 containing 3% sucrose at 25 degrees C for nearly one month. After incubation, the medium free from cells was extracted with ether 3 times. After evaporation, the residue of the ether extract was employed to determine the content on TLC and HPLC. The results showed that the incubation system mentioned above could continuously secrete the main components of S. miltiorrhiza, tanshinone IIA and cryptotanshinone, which were almost the same as the extract of S. miltiorrhiza roots. In addition, suspension incubation of callus tissue cells, the conditions of immobilization with alginate, the stability of immobilized cells and the characteristics of products were also examined. PMID- 2104211 TI - Study on the protoplast fusion between a thermotolerant yeast and Saccharomyces cerevisiae. AB - Intergenetic protoplast fusion between Saccharomyces cerevisiae 396 and thermotolerant yeast Candida sp. C6 has been studied. 396 is a molasses distiller's yeast, and C6 which was isolated from the hot spring in Yunnan, grows well at 45 degrees C. The auxotrophic mutants of 396 (Arg.) and C6 (Lys.) were obtained by treatment of NTG. The fusion frequency was 0.91 per 10(5) protoplasts. Six fusants were studied, the average size of their cells is 1.3 times the size of their parents, while the DNA content is 1.6 times. Other characteristics of the fusants including colonial and cell morphology, physiology, especially in carbon sources assimilation appeared different. The possibility of heterokaryon formation was excluded except for F2 and F14. The growth curves, efficiency of sugar utilization and ethanol yield of original parents 396 and C6, immediate parents 396 (Arg.) and C6 (Lys.), fusants F1, F7, F12 and F13 have been compared at 28 degrees C, 40 degrees C and 45 degrees C. The intergenetic fusant F13 with efficiency of substrate utilization 94.3% and the final ethanol concentration 59.7 g/l at 40 degrees C has been selected. PMID- 2104212 TI - The establishment of rat hybridoma cell lines secreting McAb against strains of potato virus Y and analysis of its stability. AB - The rat splenocytes immunized with potato virus Y (PVYn) and ratmyeloma (IR983) were fused by PEG (M. W.1450). Three kinds of stable hybridoma cell lines secreting specific monoclonal antibodies (McAbs) were derived. One kind of the cell lines producing McAbs reacts to PVYn specifically. Another reacts to PVYo specifically. The third one reacts to both of the two strains. Tested by the methods of sandwich-ELISA and indirect-ELISA, all kinds of McAbs did not react to seven plant viruses: tobacco mosaic (TMV), cucumber mosaic (CMV), tobacco tech (TEV), alfalfa mosaic (AMV), turnip mosaic (TuMV), potato leaf roll (PLRV), potato virus X (PVX). The biological properties of the hybridoma cell lines and the McAbs were tested. PMID- 2104213 TI - Accessory cell-derived helper signals in human T-cell activation with phytohemagglutinin: induction of interleukin 2-responsiveness by interleukin 6, and production of interleukin 2 by interleukin 1 [corrected]. AB - Interleukins (IL-) 1 and 6 have been shown to represent accessory signals for T cell activation. In the present study, we further examined the effects of both cytokines on accessory cell-depleted human T cells stimulated with phytohemagglutinin (PHA). The addition of IL-6 to the cultures resulted in T-cell proliferation; however, IL-1 was unable to support PHA-induced T-cell growth. The addition of IL-1 consistently induced a low level of IL-2 production and strongly enhanced T-cell proliferation in the presence of IL-6. Thus, the effect of IL-1 on T-cell growth becomes apparent only in the presence of IL-6. Blocking the IL-2 receptor (IL-2R) with the monoclonal antibodies anti-Tac and MikBeta 1 (directed to the alpha and beta chains of the IL-2R, respectively) had no effect on PHA/IL 6-supported proliferation, but completely eliminated the growth-enhancing effect of IL-1. On the other hand, a neutralizing anti-IL-4-antiserum did not affect PHA/IL-6- or PHA/IL-6/IL-1-induced proliferation. Further experiments showed that IL-6 enhances T-cell responsiveness to IL-2, as evidenced by enhanced IL-2 induced proliferation. However, we could not find an effect of IL-6 on the expression of IL-2R as measured by staining with anti-Tac and with MikBeta 1 or by binding of (125I)-IL-2 to T cells. It can be concluded from these studies that IL-1 and IL-6 have different helper effects on PHA-induced T-cell activation. In the presence of PHA, IL-6 induces limited IL-2/IL-4-independent growth, and more importantly it renders T cells responsive to IL-2. IL-1 provides a signal leading to IL-2 production. The combination of IL-1 and IL-6 represents a synergistic helper signal, leading to an IL-2-dependent pathway of proliferation. PMID- 2104214 TI - Interleukin 7 and interleukin 4 stimulate human thymocyte growth through distinct mechanisms. AB - One of the major functions of cytokines is their ability to regulate cell growth and differentiation. The complexity of this process has been highlighted by recent studies on murine thymocytes; it has been shown that a number of cytokines interact to regulate thymocyte growth. We have investigated the effects of interleukin 4 (IL-4) and interleukin 7 (IL-7) on human thymocyte proliferation. Although maximal proliferation was dependent upon the presence of the mitogen phytohaemagglutinin (PHA), IL-7 alone stimulated thymocyte growth. In order to determine if this proliferation was due to the induction of IL-2, this pathway was inhibited by the addition of blocking antibody to the IL-2 receptor. Proliferation induced with IL-7 plus PHA, but not that induced by IL-7 alone, could be blocked by this treatment. In contrast, IL-4 stimulated thymocyte proliferation only in the presence of PHA; this proliferation was not inhibited by antibodies to the IL-2 receptor. Our findings show that both IL-7 and IL-4 can act as growth factors for human thymocytes, and that these cytokines stimulate proliferation through distinct mechanisms. PMID- 2104215 TI - Cytokines in skin lesions of psoriasis. AB - Cytokine levels were compared in aqueous extracts of stratum corneum from psoriatic lesions and normal heel. Samples from heel contained high levels of interleukin-1 alpha (IL-1 alpha) and beta measured in immunoassays, although only the IL-1 alpha was biologically active. No other cytokines could be detected in heel samples. Interleukin-1 (IL-1) levels were dramatically reduced in lesional samples. A neutrophil chemoattractant was found in all lesional extracts, and was demonstrated to be mainly interleukin-8 (IL-8) using a specific neutralizing antiserum. Tumor necrosis factor alpha (TNF-alpha) and beta (TNF-beta), and interferon alpha (IFN-alpha) and gamma (IFN-gamma) were detected in lesional extracts using immunoassays, however, no equivalent biological activities could be detected. Interleukins 2 (IL-2), 4 (IL-4), and 6 (IL-6), granulocyte and granulocyte/macrophage colony stimulating factor (GM-CSF), could not be detected in any samples. IL-8 is therefore the only biologically active cytokine shown in this study to be elevated in psoriatic lesional extracts, and may therefore play a role in the pathogenesis of the disease. PMID- 2104216 TI - Characterization of granulocyte chemotactic activity from human cytokine stimulated chondrocytes as interleukin 8. AB - Human articular chondrocytes, when stimulated with interleukin 1 beta (IL 1 beta), tumor necrosis factor-alpha (TNF-alpha), or with the double stranded RNA poly (rI).poly (rC), produce a chemotactic activity for granulocytes. The induction with IL 1 beta could be abolished by an antibody to IL 1 beta but not by an antibody to interleukin 6 (IL 6), indicating that the latter is not a mediator for the production of chemotactic activity. The inducers had no direct chemotactic effect on granulocytes. The granulocyte chemotactic factor from chondrocytes was characterized with a specific antibody against leukocyte-derived interleukin 8 (IL 8). The specificity of this antibody was demonstrated by immunochemical and biological criteria such that it could immunoprecipitate only the 6-7 kDa IL 8 protein from fibroblasts, and that it did not neutralize a structurally related monocyte chemotactic protein. This antibody against IL 8 completely neutralized the granulocyte chemotactic activity from stimulated chondrocytes. This demonstrates the identity of chondrocyte IL 8 with leukocyte- and fibroblast-derived IL 8. Our data show that leukocyte chemotaxis into the inflamed joint can be mediated by IL 8, induced in both synovial fibroblasts and chondrocytes by the inflammatory cytokines IL 1 and TNF-alpha. PMID- 2104217 TI - Production of a 26,000-dalton interleukin 1 inhibitor by human monocytes is regulated by granulocyte-macrophage colony-stimulating factor. AB - An interleukin 1 (IL 1) inhibitor is secreted into culture medium by a human promyelocytic cell line, H-161, upon stimulation with (PMA) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Since the morphological characteristics of this cell line were macrophage-like, human monocytes were tested for their ability to produce similar activity using the same induction conditions. Upon induction of adherent peripheral blood monocytes with rhGM-CSF and/or PMA, an IL 1 antagonistic activity was found in the cell supernatants, as determined by IL 1 receptor binding assay, using the murine EL 4.6.1C10 cell line as the cell target. Most of the inhibition of IL 1 binding induced by PMA or by PMA/rhGM-CSF was shown to be caused by IL 1, since it was neutralized by a mixture of anti-IL 1 alpha/beta antibodies and was active in the murine thymocyte proliferation assay (LAF). The activity induced by GM-CSF alone was not neutralized by anti-IL 1 alpha/beta antibodies and showed no LAF activity. The IL 1 inhibitor activity was induced by rhGM-CSF with a D50 around 40 pg/ml. The activity was produced for more than 3 wk in the presence of GM-CSF; removal of GM-CSF was followed by a rapid decrease of IL 1 antagonistic activity. The specific binding of biosynthetically labeled IL 1 inhibitor to target cells (EL-4.6.1C10) showed a protein of 26 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). This molecule shares biological and physical characteristics with the urinary IL 1 inhibitor and the promyelocytic H-161-derived IL 1 inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104218 TI - Autocrine regulation of rheumatoid arthritis synovial cell growth in vitro. AB - Rheumatoid arthritis (RA), and not osteoarthritis (OA) synovial cells proliferate in serum-free medium, a finding that suggests that, in vitro, RA synovial cells may be stimulated to grow by the continuous autocrine production of at least one polypeptide growth factor. Adding monoclonal antibody 1D11.16, or rabbit polyclonal anti-tumor growth factor beta (anti-TGF-beta) antibodies (both neutralizing antibodies to TGF-beta 1 and TGF-beta 2) to RA synovial cells, in culture, caused a significant reduction in cell growth, an effect not seen when other growth factor antibodies (platelet-derived growth factor [PDGF], epidermal growth factor [EGF], or EGF receptor) were added to the culture medium. Taken together, these data are consistent with the concept that RA synovial cell growth in vitro is driven endogenous TGF-beta. Moreover, when EGF was added to the culture medium, this caused the numbers of RA, and not OA, synovial cells to increase significantly. This finding suggests that RA synovial cells are in G1 phase of the cell cycle; an effect that could be mediated by endogenous TGF-beta. PMID- 2104219 TI - Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1. AB - Macrophages are essential for normal wound repair and many of their effects on healing wounds are likely to be mediated by the secretion of cytokines. This study examines the appearance of messenger RNA (mRNA) for cachectin/tumor necrosis factor (TNF), IL 1, and macrophage inflammatory proteins 1 and 2 (MIP-1 and MIP-2), as well as the mature peptides, in a model of wound healing using wound chambers. RNA for all four cytokines can be detected in wound inflammatory cells by polymerase chain reaction amplification throughout the first 7 days. Cachectin/TNF and IL 1 protein levels peaked on the first day after wound chamber implantation, and MIP-1 and MIP-2 were detected only on day 3. The data suggest that these cytokines participate in the early inflammatory response to wounding. PMID- 2104220 TI - Hemorrhage induces an increase in serum TNF which is not associated with elevated levels of endotoxin. AB - Although tumor necrosis factor (TNF) and interleukin 6 (IL 6) are purported to be important mediators of inflammatory responses following trauma, it is not known if the serum levels of these cytokines are altered by simple hemorrhage. The objective of this study therefore was to determine whether or not: 1) there is any elevation of TNF or IL 6, and 2) if endotoxin, an important upregulator of these cytokines, is also increased following hemorrhage. To study this, C3H/HeN mice were bled to, and maintained at a mean blood pressure of 35 mmHg for 60 min, and then resuscitated with their own shed blood and adequate fluid. Mice were sacrificed at 30 min into hemorrhage and at 2, 4 or 24 hr post-hemorrhage to obtain serum samples. IL 6 and TNF levels were measured using cytokine dependent cellular assays. Using a quantitative Limulus amebocyte lysate assay, endotoxin levels were determined. TNF levels were significantly elevated at 30 min into hemorrhage, remaining so at 2 hr after resuscitation, but absent by 4 hr. Although there was a trend toward elevated IL 6 levels at 2 hr following hemorrhage, which was sustained up to 24 hr, the values were not significantly different from sham controls. When compared to controls, no marked increase in endotoxin was seen at any time point during or following hemorrhage. These results indicate that hemorrhage, in the absence of significant tissue trauma, causes enhanced TNF release which is not the result of increased endotoxin. PMID- 2104221 TI - Detection of urinary TNF, IL 1, and IL 2 after local BCG immunotherapy for bladder carcinoma. AB - Intravesical application of bacillus Calmette-Guerin (BCG) is highly active against recurrences of superficial urothelial bladder carcinoma. In an attempt to monitor the immunological effects of this therapy, we analyzed the urine of patients following the sixth intravessical instillation, to show the presence of the monokines TNF and IL 1 and the lymphokine IL 2. Within 24 hours following the instillation, all (n = 10) patients exhibited a strong increase in urinary cytokine secretion, which was significantly different from the control group (n = 10), with respect to TNF L929 biological assay (P less than 0.01), TNF sandwich ELISA (P less than 0.01), IL 2 CTL 6 biological assay (P less than 0.05), IL 2 sandwich-ELISA (P less than 0.005), and IL 1 sandwich-ELISA (P less than 0.05), but not to the IL 1 fibroblast biological assay. The maximum urinary secretion varied between individual patients and different cytokines, but was generally found within 2 to 8 hr after the instillation. A persistent high urinary activity was demonstrated in BCG-treated patients for IL 2 in sandwich-ELISA. These results reflect the local inflammatory response to BCG and suggest an immunomodulatory mode of action against urothelial carcinoma cells. Elucidation of the possible role of each urinary cytokine against this cancer warrants further investigations. PMID- 2104222 TI - Specific radioimmunoassays for IL 1 alpha and IL 1 beta in plasma at physiological and acidic pH: determination of immunoreactive forms by gel filtration and radioligand binding studies. AB - We have developed specific radioimmunoassays for interleukin 1 alpha (IL 1 alpha) and interleukin 1 beta (IL 1 beta) and applied these successfully to the measurement of interleukin 1 (IL 1) in neat plasma. Further characterization of the plasma immunoreactive forms of IL 1 was done using Sephadex G-75 chromatography and TSKG2000 high performance gel permeation chromatography. This revealed the immunoreactivity to be associated with a high molecular weight fraction for both IL 1 alpha and IL 1 beta. Incubation of plasma with iodinated IL 1 alpha and beta showed that there was a time-dependent association of tracer with the high molecular weight fraction and that this was predominantly with IL 1 beta. The activity was displaceable with unlabeled IL 1 beta, which together with the chromatography results, suggested that IL 1 beta is protein-bound in plasma. Furthermore, we have shown that under acid conditions both tracer and endogenous IL 1 beta immunoreactivity migrate as a low (17 kD) molecular weight fraction. This suggests that dissociation from a high molecular weight binder has occurred. Acid treatment of plasma raised the immunoreactive IL 1 beta level, but had no effect on IL 1 alpha levels, confirming the specificity of a binder to IL 1 beta, as shown by the tracer experiments. These results suggest that plasma contains high molecular weight binders of IL 1, particularly IL 1 beta, and that these may play a role in regulating the distribution, clearance and bioactivity of circulating IL 1. PMID- 2104223 TI - In vivo evidence that the rise in plasma IL 6 following injection of a fever inducing dose of LPS is mediated by IL 1 beta. AB - Although it has often been speculated that Interleukin (IL) 1 alpha and IL 1 beta are circulating endogenous pyrogens (EP), there are few data demonstrating an elevation of these cytokines in the plasma of febrile animals. We hypothesized that IL 1 is released locally and may act to stimulate the release of another pyrogen, IL 6, which circulates to the brain to cause fever. The major purpose of the present study was to determine whether pretreatment of rats with antiserum to IL 1 beta, which attenuates lipopolysaccharide (LPS) induced fever, also results in an attenuation of the rise in plasma and cerebrospinal fluid (CSF) concentrations of IL 6. Our results show that injection of IL 1 beta produced dose-dependent rises in temperature and increases in plasma and CSF IL 6 activity, and that pretreatment of rats i.v. with antiserum to IL 1 beta produced a 55% decrease in the fever caused by LPS injection, a 68% decrease in plasma IL 6, and a 67% decrease in CSF IL 6. These data confirm the findings of previous studies that IL 1 beta is required for a portion of LPS-induced fever and also provide the first in vivo demonstration that the rise of IL 6 in rats injected with a fever-inducing dose of LPS can be significantly blocked by antiserum to IL 1 beta. Overall, the data in our study can be interpreted as being consistent with the hypothesis that the pyrogenic effect of IL 1 beta is mediated mainly through the release of IL 6, but conclusive confirmation of this hypothesis must await studies with antibodies to IL 6. PMID- 2104224 TI - Transforming growth factor beta induces the production of interleukin 6 by human peripheral blood mononuclear cells. AB - Previous studies have indicated that the cytokine transforming growth factor beta 1 (TGF beta 1) has immunosuppressive properties and can inhibit the production of tumor necrosis factor (TNF) and Interleukin 1 (IL 1) by human peripheral blood mononuclear cells. In this study, we have examined the effects of TGF beta 1 on the production of Interleukin 6 (IL 6) by human peripheral blood mononuclear cells. Treatment with only TGF beta 1 leads to the induction of IL 6, and this was both dose- and time-dependent. The effect of TGF beta 1 was evident at the level of IL 6 mRNA, suggesting TGF beta 1-induced de novo synthesis of IL 6. Induction of IL 6 by TGF beta 1 was specific, as other cytokines made by mononuclear cells (TNF and IL 1) were not induced by TGF beta 1. Furthermore, when a panel of stimuli were compared for their ability to induce IL 1, TNF and IL 6 in the presence or absence of TGF beta 1, IL 6 levels were augmented in the presence of TGF beta 1, while the induction of IL 1 and TNF was inhibited significantly. These results indicate that TGF beta 1 has complex effects on the production of cytokines by peripheral blood mononuclear cells and that TGF beta 1 is not inhibitory for all cytokine production. The ability of TGF beta 1 to induce IL 6 suggests that IL 6 may mediate some of the effects of TGF beta 1. PMID- 2104225 TI - IL 3 and IL 6 do not induce bone resorption in vitro. AB - Bone resorption in vitro and in vivo can be induced by interleukin 1 (IL 1) and tumor necrosis factor (TNF), both of which are potent inflammatory cytokines. Additionally, there are other factors produced by cells which can active osteoclasts. Because diverse factors are involved in bone resorption, we examined the role of two other inflammatory cytokines, IL 3 and IL 6. IL 3 has been shown to induce the formation of osteoclast-like cells from precursors, while IL 6 is a potent mediator of inflammatory responses. Osteoclast activity in neonatal mouse calvaria was measured as 45Ca released into the supernatant fluid following a 48 hr incubation period with cytokine. Our results show that while parathyroid hormone (PTH) and IL 1 are potent inducers of bone resorption, neither IL 3 nor IL 6 displayed such activity. PMID- 2104226 TI - Effects of interferon-alpha in patients with AIDS-associated Kaposi's sarcoma are related to blood interferon levels and dose. AB - Definition of improved therapeutic regimens of interferon-alpha (IFN-alpha) for the treatment of Kaposi's sarcoma (KS) would be useful since currently recommended doses are sometimes associated with unacceptable toxicity. IFN concentrations were measured in serum samples from men with AIDS-associated KS who were enrolled in a trial of IFN-alpha alone (16 patients) or a trial of IFN alpha combined with zidovudine (25 patients). Analyses were done to examine the relationship between the dose of IFN-alpha, blood level of IFN, and the patient's clinical response to treatment. There was no correlation between dose of zidovudine given and response. As expected, there was a high correlation between dose of IFN-alpha and blood level in both studies (p less than 0.001). Furthermore, we found relationships between clinical response and both dose of IFN-alpha and blood level achieved. In the two studies combined, among men with greater than 200 CD4+ cells/mm3 of blood at baseline on average daily doses of greater than or equal to 10 million international units (MIU) of IFN-alpha, 13/19 (68%) responded compared to 6/17 (35%) on less than MIU (p = 0.05). Similarly, of men with IFN blood levels greater than or equal to 100 IU/mL 12/16 (75%) responded compared to 7/20 (35%) of those with blood levels less than 100 IU/mL (p = 0.02). The dose and blood levels of IFN achieved and maintained may be important factors in determining responses of KS. Additional clinical trials of IFN-alpha treatment of KS at doses about 10 MIU/day appear warranted. PMID- 2104227 TI - Lipopolysaccharide-induced production of cytokines by bone marrow-derived macrophages: dissociation between intracellular interleukin 1 production and interleukin 1 release. AB - We investigated the capacity of mouse bone marrow-derived macrophages (BMDM) to produce interleukin 1 (IL 1), interleukin-6 (IL 6), and tumor necrosis factor (TNF) upon lipopolysaccharide (LPS) stimulation. BMDM were allowed to differentiate either in the presence of conditioned medium (from WEHI-3 or L cells), or in the presence of recombinant cytokines (IL 3, macrophage-colony stimulating factor [M-CSF], or granulocyte/macrophage-colony stimulating factor [GM-CSF]). Cells were maintained in culture up to 3 weeks and tested at different times. Significant spontaneous cytokine production was never observed. BMDM rapidly acquired the capacity to elaborate cytokine upon LPS activation. LPS triggered BMDM were able to produce IL 1, IL 6, and TNF, throughout the culture period, although 2- to 3-week-old cells lost their ability to release IL 1 while accumulation of intracellular IL 1 remained unchanged. The dissociation between synthesis and release of IL 1 was not correlated with a significant modification of the specific binding of LPS onto the cell surface. PMID- 2104228 TI - Interleukin 2 produced by activated B lymphocytes acts as an autocrine proliferation-inducing lymphokine. AB - Normal peripheral blood B cells produce a soluble factor after activation that is functionally indistinguishable from interleukin 2 (IL 2) and can support B cell proliferation in vitro. Purified rabbit peripheral blood B cells, when stimulated with a combination of ionomycin (0.5 microgram/mL) and phorbol myristate acetate (PMA) (1 ng/mL), secreted a soluble factor in the culture medium that supported the IL 2-dependent cell line CTLL-2. The ability of these supernatants to support CTLL-2 growth was almost completely blocked by rabbit antibodies against human recombinant IL 2 and by the anti-IL 2 receptor monoclonal antibody 7D4. These data strongly suggest that the growth factor secreted by rabbit B cells is IL 2. To examine the possibility that the IL 2 activity detected in the B-cell cultures may be derived from residual T cells, B cells were further purified by successive panning with a pan-T-cell monoclonal antibody, L11-135, and goat anti-rabbit IgG. These highly purified B cells produced levels of IL 2 activity comparable to those produced by the initial B cell populations. Comparison of IL 2 production by decreasing numbers of purified T cells and purified B cells also indicated that the B cells were the source of IL 2 activity. Supernatants of activated B cells could support proliferation of B-cell blasts, and this activity could be completely absorbed by CTLL-2 cells, indicating that IL 2 is a major growth factor for B cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104229 TI - Polypeptide growth factors augment interleukin 1-induced release of prostaglandin E2 by rheumatoid arthritis synovial cells in vitro. AB - When stimulated with increasing amounts of interleukin 1 beta (IL 1 beta) rheumatoid arthritis (RA), as compared with osteoarthritis (OA), synovial cells grown in RPMI plus fetal bovine serum (FBS), released significantly more prostaglandin E2 (PGE2) (p less than 0.05; paired t test, two-tailed). PGE2 release by IL 1 beta-stimulated RA synovial cells grown for 14 days in serum-free RPMI was significantly less than that released by the same cells grown in medium plus 10% FBS (p less than 0.03; two-tailed). Since these data suggest that growth factors present in FBS may augment the effects of IL 1 beta, experiments were conducted to study the influence of four polypeptide growth factors--transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), on IL 1 beta induced release of PGE2 by cultured RA synovial cells. Both EGF and bFGF significantly enhanced IL 1 beta-induced release of PGE2 (p less than 0.05; paired t test, one-tailed), while PDGF was synergistic with IL 1 beta, significantly increasing release of PGE2 by these cultured cells (p less than 0.02; two-tailed). No such effect was seen when TGF-beta was added to the culture medium. Taken together, these data lend support to the concept that within the synovial micro-environment small quantities of individual growth factors may potentiate the effects of IL 1 beta to amplify intra-articular inflammation. PMID- 2104230 TI - The effects of pentoxifylline on lipopolysaccharide (LPS) fever, plasma interleukin 6 (IL 6), and tumor necrosis factor (TNF) in the rat. AB - The purpose of these studies was to test whether pentoxifylline, a drug that can inhibit the production and action of cytokines hypothesized to be endogenous pyrogens (for example, interleukin 1 and tumor necrosis factor [TNF]), is antipyretic. We also tested the effects of pentoxifylline on plasma activities of interleukin 6 (IL 6) and TNF in response to an injection of a fever-inducing dose of lipopolysaccharide (LPS). Our results showed that a high dose of pentoxifylline (200 mg/kg) caused hypothermia in control rats and blocked LPS fever, while a low dose (50 mg/kg) did not have these effects. Injection of the high dose of pentoxifylline in control rats caused a rise in plasma IL 6 but not in plasma TNF. However, the peak levels of plasma IL 6 and TNF activities following an injection of LPS were significantly reduced by pretreatment with pentoxifylline. Overall, the data are consistent with the hypothesis that pentoxifylline is an antipyretic drug, which may act at least in part by inhibiting the secretion of pyrogenic cytokines. PMID- 2104231 TI - Infectious complications of interleukin 2 therapy. PMID- 2104232 TI - Tumor necrosis factor beta (TNF-beta) induces binding of the NF-kappa B transcription factor to a high-affinity kappa B element in the TNF-beta promoter. AB - The expression of the gene encoding tumor necrosis factor beta (TNF-beta) (lymphotoxin) is induced in T cells by various extracellular stimuli. We noticed that most such stimuli also activate the NF-kappa B transcription factor. Here we demonstrate binding of purified human NF-kappa B to a sequence within positions 98 to -88 (5'-GGGGCTTCCCC-3') of the TNF-beta promoter, which is conserved between the human and mouse genes. Also the NF-kappa B from the human T-cell line Jurkat, activated upon phytohemagglutinin (PHA)/phorbol 12-myristate 13-acetate (PMA/TPA) treatment in vivo or upon deoxycholate treatment in vitro, binds with high affinity to the sequence in the TNF-beta promoter. Apart from a single mismatch, the site is identical to a cis-activating element that is involved in the inducible expression of the MHC class I gene H-2Kb and which interacts with both the inducible NF-kappa B transcription factor and the constitutive factor KBF1/H2TF1, as we demonstrate here for the site in the TNF-beta promoter. The high homology of the well characterized H-2Kb enhancer sequence with the TNF-beta site with regard to sequence and factor binding strongly supports a physiological role for NF-kappa B in the inducible expression of the TNF-beta gene. Our observation that the TNF-beta protein can rapidly induce the DNA-binding activity of NF-kappa B in Jurkat T cells and transiently increase TNF-beta mRNA levels suggests that NF-kappa B can mediate a positive autoregulation of TNF-beta synthesis. PMID- 2104233 TI - A soluble form of the interleukin 4 receptor in biological fluids. AB - Murine biological fluids and murine cell culture supernatants were analyzed for the presence of soluble murine interleukin 4 receptor (sIL4R) with the use of two monoclonal antibodies directed against the receptor. Mouse urine, serum, ascitic fluid, and cell culture supernatants contained varying levels of immunoreactive protein. All of the immunoreactive protein possessed interleukin 4 (IL 4) binding activity. Following partial purification of ascitic fluid a protein was isolated that binds IL 4 with high affinity. This data is consistent with the fact that murine biological fluids contain a soluble version of the murine IL 4 receptor that arises via secretion of the soluble receptor and/or via shedding of the extracellular portion of the full-length receptor from the cell surface. PMID- 2104234 TI - Characterization of a T-cell-derived mast cell costimulatory activity (MCA) that acts synergistically with interleukin 3 and interleukin 4 on the growth of murine mast cells. AB - The proliferation of mucosal mast cells (MMC) depends on the presence of interleukin 3 (IL 3) and can be further enhanced by interleukin 4 (IL 4). The supernatant of a TH2 cell clone (ST2/K.9) stimulated by concanavalin A was found to contain a factor, provisionally termed mast cell costimulatory activity (MCA), that substantially enhances the proliferation of MMC promoted by a combination of IL 3 and IL 4. In comparison to other lymphokines MCA is rather resistant to tryptic digestion but is very sensitive to pH values lower than 6.0 and to organic solvents. Chromatographic fractionation of MCA revealed that activity is associated with protein(s) or glycoprotein(s) of 35 to 40 kDa. Partially purified MCA that was functionally free of other T-cell-derived lymphokines did not stimulate mast cell proliferation in the absence of a combination of IL 3 and IL 4. In addition, MCA did not affect the proliferation of mast cells when employed together with either IL 3 or IL 4 alone. Control experiments demonstrated that MCA is identical to neither the T-cell-derived lymphokines IL 2 to IL 6, IL 9, interferon gamma, tumor necrosis factor alpha or beta, or granulocyte-macrophage colony-stimulating factor (CSF), nor to IL 7, granulocyte CSF, macrophage CSF, erythropoietin, leukemia inhibitory factor, or epidermal growth factor (EGF). Finally, experiments using a panel of PPD-reactive TH1- and TH2-like cell lines revealed that MCA is preferentially produced by TH2 cells. These data, especially the relative resistance of MCA to trypsin and the high sensitivity to low pH values and organic solvents, indicate that MCA is distinct from known T-cell derived lymphokines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104235 TI - Fate of injected interleukin 1 in rats: sequestration and degradation in the kidney. AB - The tissue distribution and route of clearance of human recombinant interleukin 1 alpha (IL 1 alpha) injected intravenously in rats was studied. The plasma half life was approximately 2.5 min, and this was increased after nephrectomy, the kidney being the major organ through which the IL 1 alpha was excreted. Two iodinated fragments of IL 1 alpha, of approximately 5 and 9 kDa, were excreted by the kidneys whereas only intact, 17-kDa IL 1 alpha was detected in plasma, suggesting that the protein was being degraded after uptake by the kidney. The results of in vivo experiments in which surface endopeptidase-24.11 was inhibited with phosphoramidon and in vitro experiments in which rat kidney homogenates were incubated with radiolabeled IL 1 alpha suggest that the cytokine was endocytosed and then hydrolysed by lysosomal proteinases. PMID- 2104236 TI - Temporal sequence of interleukin 1 alpha-mediated stimulation and inhibition of bone formation by isolated fetal rat calvaria cells in vitro. AB - Cytokines released at sites of inflammation and infection may alter normal bone remodeling processes resulting in pathologic bone destruction or bone formation. Interleukin 1, an inflammatory mediator, has been shown to stimulate as well as inhibit parameters associated with bone formation. In this study we have examined temporal aspects of the biphasic effects of recombinant interleukin 1 alpha (IL 1 alpha) on the differentiation of osteoprogenitor cells into bone-forming osteoblasts (bone nodules) in vitro. A dose-dependent stimulation of bone formation over a concentration range of 0.5 to 50 U/mL (1.4 x 10(-12) to 1.4 x 10(-10) M) was observed when preconfluent, primary cultures of fetal rat calvaria (RC) cells were pulsed with IL 1 alpha for 72 to 96 hr from the beginning of the culture period. This was correlated with a stimulation of cell proliferation and alkaline phosphatase activity measured during the late log phase of growth. In contrast, continuous exposure to IL 1 alpha or exposure to IL 1 alpha after confluency resulted in inhibition of bone nodule formation and alkaline phosphatase activity. IL 1 alpha-stimulated prostaglandin E2 (PGE2) production until the RC cells became multilayered, but the addition of the cyclooxygenase inhibitor indomethacin had no effect in reducing the IL 1 alpha-mediated stimulation of cell proliferation or bone nodule formation. However, in cultures continuously exposed to IL 1 alpha, added indomethacin partially reduced the inhibition of bone formation, suggesting that prostaglandin production may play a role in the inhibitory effects of IL 1 alpha on bone formation. PMID- 2104237 TI - Biologically active interleukin 1 in human eccrine sweat: site-dependent variations in alpha/beta ratios and stress-induced increased excretion. AB - Human eccrine sweat devoid of epidermal protein contamination was collected from palms, soles, and different sites on the trunk. Interleukin 1 alpha (IL 1 alpha) and interleukin 1 beta (IL 1 beta) content were analyzed for immunoreactivity by enzymo-immunoassay and immunoblotting and for bioactivity by the stimulation of prostaglandin E2 (PGE2) production in human dermal fibroblasts. The bioassay was validated by using blocking antibodies against IL 1 alpha and beta. All sweat samples were found to contain significant amounts of immunoreactive and biologically active IL 1. The immunoreactive forms were at 17 kDa as shown by immunoblotting analysis, indicating that they were mature (secreted), undegraded IL 1 peptides. Whereas IL 1 alpha was detectable in sweat samples obtained from both truncal and palmo-plantar regions, IL 1 beta was only detectable in the sweat of palms and soles (IL 1 alpha/beta ratio greater than 700 in trunk and 5.4 in palms and soles) indicating a site-dependent difference in the excretion of the two IL 1 molecules. IL 1 concentration was high in spontaneous (IL 1 alpha, 3.7; IL 1 beta, 0.3 ng/mL) and pilocarpine induced sweat (IL 1 alpha, 3.9; IL 1 beta, 1.2 ng/mL), and it was much increased during jogging and sauna (IL 1 alpha, 22.6; IL 1 beta, 3.3 ng/mL). This does not appear to represent an excretory process aimed at clearing blood IL 1, but rather a stress-induced increased production of IL 1 by sweat gland cells. PMID- 2104238 TI - Tumor necrosis factor alpha induction in human monocytes. AB - The present study was undertaken to assess the presence of tumor necrosis factor (TNF)-alpha mRNA and protein in circulating human blood monocytes and to study the TNF-alpha gene expression in human monocytes isolated by continuous Percoll gradient fractionation. The technique of RNA isolation directly from the blood samples was used to study TNF-alpha mRNA expression in circulating human blood leukocytes. It was shown that human blood leukocytes of healthy donors contained no presynthesized pool of TNF-alpha mRNA as well as no TNF-alpha protein. It was found that early pretreatment with cycloheximide interferes with TNF-alpha mRNA induction by Staphylococcus aureus. PMID- 2104239 TI - Immunopathogenesis and immunotherapy of chronic arthritis. PMID- 2104240 TI - Induction of interferon-beta and 2'5'-oligoadenylate synthase mRNAs by interleukin 6 during the differentiation of murine myeloid cells. PMID- 2104241 TI - Interleukin-6 is the central tumor growth factor in vitro and in vivo in multiple myeloma. AB - When bone-marrow cells from patients with multiple myeloma (MM) were seeded in short-term cultures, a spontaneous proliferation of the myeloma cells occurred for most of the patients with active disease and proliferating myeloma cells in vivo. In all cases, this spontaneous proliferation was inhibited by anti-IL-6 monoclonal antibodies (mabs). Moreover, myeloma cell lines, completely dependent upon exogenous IL-6 for their growth, could be reproducibly established by initially stimulating the myeloma cells with both IL-6 and GM-CSF. These results demonstrate that IL-6 is a major paracrine myeloma-cell growth factor in vitro. High serum IL-6 levels were observed in MM patients with active disease, especially patients with terminal disease. High IL-6 mRNA levels were found in bone-marrow cells of MM patients, mainly in myeloid and monocytic cells, in vivo. The myeloma cells did not express IL-6 mRNA. Injection of anti-IL-6 mabs to MM patients with terminal disease and extramedullary proliferation, completely blocked the myeloma-cell proliferation in vivo and completely inhibited the serum IL-6 bioactivity and the serum CRP levels. One patient with plasma cell leukemia and hypercalcemia was treated for two months with anti-IL-6 mabs and maintain in remission for 2 months without major side effects. Interestingly, the serum calcium levels also decreased in these patients. All these results show that IL-6 is the main cytokine responsible not only for the myeloma-cell proliferation in vivo, but presumably also for the large bone resorption processes observed in human MM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104242 TI - Implications of cytokines in immunopathology: experimental and clinical data. PMID- 2104243 TI - TNF alpha enhancement of NK and LAK cell functions induced by high-dose IL-2 in human peripheral blood mononuclear cells from patients pretreated with alpha IFN + IL-2. AB - In this study we analyzed the induction of NK and LAK cell functions by TNF alpha, alone or combined with IL-2, in 4 days in vitro culture of PBMC from patients treated with alpha IFN + IL-2. Although the MN cell recovery after 4 days culture was very similar with TNF alpha alone or with IL-2 alone, TNF alpha did not maintain nor induce LAK or NK activities of in vivo preactivated PBMC. When compared to preculture values, TNF alpha alone induced a preferential outgrowth of CD4+ T cells together with a decrease of CD8+ T cells, NK cells and IL-2R (p55)-expressing cells. The combination of TNF alpha (100 ng) and high dose IL-2 (9,000 IUg/ml) did not improve the MN cell recovery after 4 days culture; but increased IL-2-induced NK activities in PBMC from 6/7 patients, and IL-2 induced LAK activities in 4/7 patients. However, these variations were not significant. The combination of TNF alpha and lower doses of IL-2, ranging from 150 IU/ml to 30 IU/ml, did not modify MN cell recovery in culture nor IL-2 induced NK and LAK cell activities. When compared to paired samples cultured with IL-2 alone, the combination of TNF alpha with all doses of IL-2 did not modify the distribution of T and NK cells, but increased the expression of CD8 on NK cells. Furthermore, the combination of TNF alpha and IL-2 increased the expression of IL-2R (p55) on PBMC but the expression of this receptor was restricted to CD4+ T cells and did not appear on NK cells. PMID- 2104244 TI - Interleukin-2 regulation of diadenosine 5',5'''-p1 p4-tetraphosphate (Ap4A) levels and DNA synthesis in cloned murine T lymphocytes. AB - The levels or diadenosine 5', 5'''-p1, p4, tetraphosphate (Ap4A), a putative signal molecule associated with DNA synthesis, has been measured in murine T lymphocytes. The level or Ap4A detected correlated with the stimulation of DNA synthesis in murine T lymphocytes. In interleukin-2 (IL-2) dependent cells previously deprived of IL-2, new DNA synthesis can be induced by adding IL-2; the synthesis of DNA is preceded by an increase in Ap4A levels. A significant increase in DNA synthesis was observed after the Ap4A concentration exceeded the Kd of DNA polymerase alpha for Ap4A. Similarly, in cells blocked from synthesizing DNA by hydroxyurea, the levels or Ap4A are maintained only in the presence of IL-2. Once IL-2 is removed, the potential to synthesize DNA decreases and is preceded by decreases in the level or Ap4A. The DNA synthesis potential decreases rapidly after the Ap4A concentration fell below the Kd of DNA polymerase alpha for Ap4A. It is possible that Ap4A is a second messenger molecule required for the proliferation of lymphocytes and that the production of Ap4A in IL-2 dependent murine T lymphocytes is regulated by the homologous growth factor. PMID- 2104245 TI - Cytokine measurements in body fluids. AB - Bioassays and immunoassays for cytokines are now widely available for use in clinical laboratories which may have little or no expertise in cytokine biology. Whilst this facilitates the accumulation of data concerning cytokine levels in body fluids in disease, it is based on the assumption that such assays can be used for this purpose. In many cases, the presence of complex interfering factors in plasma and other body fluids require that assays should be subjected to detailed assay validation before confidence can be placed on the results. It is the purpose of this report to outline the potential problems with cytokine assays and the criteria that should be applied before making measurements in biological fluids. PMID- 2104246 TI - The significance of tumour necrosis factor serum levels in organ transplantation. AB - This paper describes a detailed study of tumour necrosis factor release during the immediate post transplant period in recipients of liver and kidney allografts. The results show no correlation between levels of TNF and rejection in Azathioprine and steroid treated patients and give good correlation in cyclosporin A immunosuppressed patients. Treatment with monoclonal antibody Campath 1-G caused high levels of TNF production. Interleukin-1 levels were not associated with levels of TNF. Sequential measurements of TNF levels may provide an aid to early diagnosis of graft rejection. PMID- 2104247 TI - Less is less: less is not more. Peer review, dollars, NIH and Congress. PMID- 2104248 TI - Mediation of immune glomerular injury. AB - This paper reviews current concepts of glomerular immune injury of both inflammatory and noninflammatory types. In noninflammatory lesions induced by antibody alone or C5b-9, the glomerular epithelial cell appears to be the principal target of injury. Similar mechanisms are probably operative in human diseases such as minimal change nephrotic syndrome and membranous nephropathy. In inflammatory lesions, circulating effector cells including neutrophils, macrophages, platelets, and probably lymphocytes as well as resident glomerular mesangial cells may mediate tissue injury. Human equivalents of these inflammatory lesions include most diseases associated with mesangial and/or subendothelial immune deposits and/or mesangial cell proliferation. Neutrophil mediated injury appears to be consequent to both proteinases and oxidants, particularly the myeloperoxidase-H2O2-halide system. Platelets may be critically involved in neutrophil mediated injury as well. Platelets also mediate mesangial cell proliferation, probably by a release of platelet growth factors and stimulation of mesangial cell platelet-derived growth factor and platelet-derived growth factor receptor expression. Immunologically induced mesangial cell proliferation is associated with increased production of nephritogenic proteinase in vivo. PMID- 2104249 TI - Vitamin D metabolism and mechanisms of calcium transport. AB - Vitamin D3 undergoes sequential hydroxylations in the liver and kidney to form 1,25-dihydroxyvitamin D3, the biologically active form of the vitamin. 1,25 dihydroxyvitamin D3 is metabolized by several processes in various target tissues that decrease the biological activity of the sterol. In addition, 1,25 dihydroxyvitamin D3 is excreted in the bile as polar metabolites, such as glucuronides and, possibly sulfates and neutral polar steroids. These compounds undergo an enterohepatic recirculation in both man and experimental animals. 1,25 dihydroxyvitamin D3 increases the absorption of calcium in the intestine and the reabsorption of calcium in the kidney. It induces the synthesis of several proteins, the most notable of which is calcium binding protein that is thought to play a role in the absorption of calcium. The vitamin D-dependent calcium binding proteins and the calcium-magnesium ATPase calcium pump are co-localized in several tissues that play a role in the absorption of calcium. PMID- 2104250 TI - Effect of potassium intake on blood pressure. AB - Epidemiologic, experimental, and clinical studies suggest that potassium is an important regulator of blood pressure. Surveys conducted in widely divergent geographic locations indicate higher prevalence of hypertension in populations ingesting diets low in potassium. Amelioration of hypokalemia lowers blood pressure in mineralocorticoid-induced hypertension in rats and in essential hypertensive patients receiving thiazide diuretics. We observed that in normotensive subjects ingesting normal amounts of sodium, short-term potassium depletion increases the mean arterial pressure from 90.9 +/- 2.2 mm Hg to 95.0 +/ 2.2 mm Hg (P less than 0.01). Furthermore, acute sodium loading increases blood pressure in potassium-depleted subjects but it had no effect in subjects ingesting normal amounts of potassium. Preliminary studies indicate that short term potassium depletion also elevates blood pressure in hypertensive patients. Potassium supplementation lowers blood pressure in hypertensive patients ingesting normal amounts of sodium. Blacks appear to be more sensitive to the hypotensive effects of potassium. The mechanism of potassium-induced changes in blood pressure is not well understood. Potassium depletion consistently induces sodium retention. The hypertensive effects of potassium depletion and hypotensive effects of potassium supplementation are not observed when sodium intake is kept low. Direct vasoconstrictive effects of hypokalemia may contribute to the pressor effect of potassium depletion. The role of altered vascular sensitivity to vasoactive hormones and alterations in divalent cation metabolism in mediating the potassium-induced changes in blood pressure require further study. PMID- 2104251 TI - Cerebral circulation: humoral regulation and effects of chronic hypertension. AB - New concepts have emerged in recent years concerning regulation of cerebral circulation. The purpose of this review is to summarize briefly several of these concepts. First, humoral mechanisms may have important effects on cerebral blood vessels and blood flow to choroid plexus. Recent evidence suggests that several vasoactive peptides may have major effects on fluid and ion balance in the brain by altering blood flow to the choroid plexus and possibly the production of cerebrospinal fluid. Second, chronic hypertension produces structural remodeling and hypertrophy of cerebral blood vessels and a shift in the relationship of cerebral blood flow to systemic blood pressure. Third, endothelium-dependent responses of cerebral arterioles to receptor and nonreceptor mediated agonists are impaired during chronic hypertension. Alterations in endothelium-dependent responses of cerebral arterioles during chronic hypertension appears to be due to release of an endothelium-derived contracting factor. PMID- 2104252 TI - Adaptation to low-protein diets in renal failure: leucine turnover and nitrogen balance. AB - In normal subjects, short to intermediate responses to dietary protein restriction include decreased amino acid oxidation and protein degradation plus increased utilization of amino acids for protein synthesis; these responses are activated to improve amino acid utilization and nitrogen balance. To assess whether chronic renal failure (CRF) impairs the adaptive responses to a low protein diet, we measured nitrogen balance and the kinetics of infused L-(15N,1 13C)leucine during fasting and feeding. In six adult CRF and four control (C) subjects, 0.6 (LP) and 1.0 (HP) g protein kg-1 day-1 diets were compared. LP reduced feeding stimulated oxidation of leucine by 26% in CRF and 33% in C (P = NS). During fasting, oxidation was unaffected by diet or CRF. For both groups, feeding suppressed protein degradation to the same extent; leucine incorporation into protein did not change. Nitrogen balance during the two diets was the same with C and CRF, as was protein balance estimated from results of measured leucine kinetics. Thus, patients with CRF can activate appropriate adaptive responses to LP inasmuch as reduced amino acid oxidation occurring with feeding and estimates of protein balance did not differ from control. PMID- 2104253 TI - The National Kidney and Urologic Diseases Advisory Board report. PMID- 2104254 TI - Endothelin mediates the renal vasoconstriction induced by cyclosporine in the rat. AB - The effect of cyclosporine on renal function was first investigated in the isolated perfused rat kidney. Kidneys from normal male Sprague-Dawley rats were perfused at constant pressure. After control clearance periods, cyclosporine (0.6, 1.2, or 3 mg/min) or vehicle was infused over 5 min period in the renal artery and then four 10-min experimental periods followed. Cyclosporine, but not vehicle caused a dose dependent fall in renal perfusate flow associated with a concomitant increase in renal vascular resistance. Glomerular filtration rate was also decreased in parallel. We also examined whether endogenous endothelin mediates cyclosporine-induced acute renal vasoconstriction. In isolated kidneys pre-exposed to specific anti-endothelin antibody and then challenged with cyclosporine (1.2 mg/min) the renal perfusate flow, renal resistance, and glomerular filtration rate were 22.3 +/- 1.8 ml/min, 4.50 +/- 0.36 mmHg/ml.min-1, 1.06 +/- 0.05 ml/min, respectively, as compared with 12.9 +/- 1.2 ml/min, 7.8 +/- 1.2 mmHg/ml.min-1, 0.55 +/- 0.06 ml/min (P less than 0.01) measured in isolated kidneys pre-exposed to a non-immunized rabbit serum. The effectiveness and specificity of anti-endothelin antibody were confirmed by its capability of preventing the renal function deterioration caused by a single bolus dose (150 pmol) of synthetic endothelin, but not by infusion of angiotensin II, norepinephrine, or thromboxane A2 mimetic U-46619 in isolated kidneys. To test further the relationship between endogenous endothelin and cyclosporine-induced renal vasoconstriction, a second series of in vivo studies was performed in normal rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104255 TI - Cranial computed tomography and magnetic resonance imaging in autosomal dominant polycystic kidney disease. AB - High resolution computed tomography or magnetic resonance imaging of the head with 3-mm sections through the circle of Willis was obtained in 96 patients with autosomal dominant polycystic kidney disease. These scans are well suited for the noninvasive, presymptomatic diagnosis of intracranial aneurysms at high risk of rupture, since the risk of rupture of unruptured aneurysms is heavily dependent on their size, and aneurysms equal to or larger than 6 mm in diameter are not likely to escape detection by these techniques. No definite aneurysm was observed in any of the 96 patients. Small areas (2-4 mm) of contrast enhancement or signal void were detected in 11 patients. These areas are possibly due to vascular tortuosity, but the studies were considered to be indeterminate because a small aneurysm could not be ruled out. Cerebral angiography in two of these 11 patients was normal. Arachnoid cysts were observed more frequently in the patients with polycystic kidney disease than in a control group of patients matched by gender, age, and type and date of examination. PMID- 2104256 TI - Screening for occult intracranial aneurysms in polycystic kidney disease: interim guidelines. PMID- 2104257 TI - Regulation of parathyroid cell gene expression in experimental uremia. AB - The secondary hyperparathyroidism of renal failure is an important component of renal osteodystrophy. We studied PTHmRNA levels and their regulation in control and subtotal nephrectomized (5/6 NX) rats at 3 wk, as well as levels of the 1,25(OH)2D3 receptor mRNA in parathyroids. Serum 1,25(OH)2D levels were decreased in 5/6 NX, whereas PTHmRNA levels were increased (7 +/- 0.7 OD U, N = 4) compared to controls (2.1 +/- 1.2, P less than 0.01); both decreased after 1,25(OH)2D3 (100 pmol/100 g body weight). Similar results were found in 5/6 NX rats after 3 months. There was no change in actin mRNA levels. PTHmRNA levels were highest in 5/6 NX rats with the most severe renal failure. The parathyroid gland 1,25(OH)2D3 receptor mRNA levels were not different between 5/6 NX rats and controls and were not affected by 1,25(OH)2D3 (100 pmol/100 g body weight daily) at 1 or 3 days. PTHmRNA levels of 5/6 NX rats did not increase when the serum calcium was decreased from 2.8 +/- 0.05 mmol/L to 0.9 +/- 0.15 mmol/L at 3 or 5 h, which contrasted with the marked increase in PTHmRNA in normal rats after hypocalcemia. As in normal rats, after hypercalcemia (4.8 mmol/L at 1 h) there was no change in the 5/6 NX rats' PTHmRNA levels. These results show that 5/6 NX rats have increased PTHmRNA levels that are normally regulated by injected 1,25(OH)2D3 but not by calcium. Parathyroid gland 1,25(OH)2D receptor mRNA levels are not increased in 5/6 NX in contrast to the increased PTHmRNA, which reflects the larger glands of uremia. 1,25(OH)2D receptor mRNA levels were not regulated by 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104258 TI - Determinants of epithelial differentiation during early nephrogenesis. AB - Organogenesis from undifferentiated progenitor cells and initiation of a society's new journal are developmental processes which share common elements. Both initially require a potent inducing stimulus followed in relatively rapid sequence by the appearance of organ-specific differentiation markers. These events are prerequisites to subsequent proliferation and maturation. Insofar as many postnatal forms of renal disease (e.g., hereditary glomerulopathies, infantile and adult forms of polycystic kidney disease, congenital dysplasias) owe their origins ultimately to disordered nephrogenesis, it is my belief that research in this area of nephrology should expand. It is further hoped that JASN will adopt this particular differentiation marker and serve as a forum for reporting the much-needed new knowledge to be gained. To "induce" the Journal's activity in this area I have summarized current knowledge and suggest directions in need of further investigation. PMID- 2104259 TI - Biocompatibility of hemodialysis membranes. AB - Exposure of blood to hemodialysis membranes results in numerous interactions between the blood elements and the membrane. Transformation and adsorption of plasma proteins (such as complement) and activation of blood cells (such as neutrophils and monocytes) have been studied most extensively by nephrologists in recent years. There is no consensus on the definition of biocompatibility for dialyzer membranes. An operational definition of biocompatibility is the lack of any perturbation of blood constituents. According to this "inert surface" definition, a membrane (for example, one that adsorbs beta 2-microglobulin) can be considered as bioincompatible and yet desirable. Because of the multitude of blood-membrane interactions that may occur during hemodialysis, multiple criteria for biocompatibility needs to be applied in the classification of membranes. A certain bioincompatible phenomenon can be further classified as beneficial or deleterious depending on its biological effects as well as its acute and chronic impacts on the dialysis patient. PMID- 2104260 TI - Cellular and molecular mechanisms of cyclosporin nephrotoxicity. AB - Cyclosporin therapy is associated with several forms of nephrotoxicity, the most significant of which are reversible impairment of glomerular filtration and irreversible interstitial fibrosis. Impaired glomerular filtration is due to both reduction in Kf, the glomerular capillary ultrafiltration coefficient, and to reduction in renal blood flow. The mechanisms responsible for the low Kf are not well defined, but heightened mesangial cell contractility may contribute. Reduced renal blood flow with chronic cyclosporin therapy arises from both endothelial damage and altered eicosanoid metabolism, in particular increased thromboxane synthesis. Renal interstitial fibrosis, which develops in some patients after approximately 6-12 months of cyclosporin therapy, poses a major limitation to the chronic use of the drug. Two mechanisms likely contribute to cyclosporin associated interstitial fibrosis. First, endothelial injury and vasoconstriction produce renal ischemia, which in turn is associated with enhanced synthesis of extracellular matrix proteins. Second, cyclosporin likely influences the accumulation of matrix proteins in the renal interstitium through nonhemodynamic mechanisms, as suggested by altered matrix accumulation in non-renal tissues. This effect of cyclosporin may be direct or indirect, via mediators including cytokines, peptide growth factors, and thromboxane. The molecular mechanisms of cyclosporin action on immunologic and mesenchymal cells are active areas of investigation. Intracellular targets of cyclosporin include mitochondrial respiration, cellular calcium signaling, protein kinase C, protein synthesis, and peptidyl-prolyl isomerases. However, the significance of these intracellular effects for cyclosporin nephrotoxicity remains to be demonstrated. PMID- 2104261 TI - Greater loop chloride uptake contributes to blunted pressure natriuresis in Dahl salt sensitive rats. AB - A blunted pressure natriuretic response is present in Dahl salt sensitive rats. To determine whether this results from tubular or glomerular mechanisms, late proximal, early distal, and late distal micropuncture were performed in salt resistant (R), salt sensitive (S), or salt sensitive rats with renal perfusion reduced to that of R rats (S-AC). Differences in neuro-endocrine background between groups were eliminated by renal denervation and by fixing plasma aldosterone, norepinephrine, and vasopressin levels by infusion. Renal perfusion pressure was greater (P less than 0.05) and inulin clearance less (P less than 0.05) in S than R rats. Urinary sodium excretion, however, was not different. S AC had renal perfusion pressures that were similar to R rats and inulin clearance similar to S rats. Urinary NaCl excretion was less (P less than 0.05) than either group. Single nephron inulin clearance, fluid, and chloride delivery to late proximal sites were not different between groups. Absolute and fractional chloride delivery to early distal sites was less (P less than 0.05) in S-AC than R or S but not different between R and S. Late distal chloride delivery was not different between any group. Calculated loop chloride reabsorption was greater in S-AC than R or S. Thus, the lower urinary NaCl excretion in S-AC rats is in part due to increased loop chloride reabsorption. This effect is probably intrinsic to the S kidney as it occurs despite renal denervation when plasma levels of vasopressin, norepinephrine, and aldosterone are fixed. The increased loop chloride uptake is abolished when perfusion pressure increases. PMID- 2104262 TI - Uric acid crystal binding to renal inner medullary collecting duct cells in primary culture. AB - Attachment of microcrystals to cellular membranes may be an important component in the pathophysiology of urolithiasis. This study characterizes the concentration-dependent binding of uric acid crystals to rat renal inner medullary collecting duct cells in primary culture. Collecting duct cell cultures grew as monolayers with interspersed aggregates of rounded cells. Cultures were incubated with 14C-uric acid crystals, and the crystals that bound were quantitated by adherent radioactivity. Uric acid crystal adherence demonstrated concentration dependent saturation with a 1/alpha value (maximum micrograms of crystals adhering to 1 cm2 of binding area) of 645 micrograms/cm2. The beta values (fraction of cross-sectional area which bound crystals) of uric acid (mean = 0.15) and calcium oxalate monohydrate (mean = 0.13) crystals did not differ significantly. Uric acid crystal binding was inhibited by pre-bound calcium oxalate monohydrate crystals in a concentration dependent manner. These data suggest that uric acid and calcium oxalate crystals exhibit similar binding patterns to rat renal inner medullary collecting duct cells in primary culture. PMID- 2104263 TI - Effect of propranolol on phosphate reabsorption by superficial nephron segments in response to parathyroid hormone in phosphate-deprived rats. AB - Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone. The decreased phosphaturic response to parathyroid hormone in rats fed a low phosphate diet for 1 day can be restored by propranolol infusion. Free-flow micropuncture studies were performed to localize the nephron site of restoration of the phosphaturic effect of parathyroid hormone by propranolol in rats deprived of phosphate for one day. In animals fed low phosphate diet and in the presence of parathyroid hormone, propranolol infusion did not change phosphate delivery to the late proximal tubule; however, fractional delivery of phosphate to the early distal tubule was significantly increased from 18.3 +/- 2.9 to 32.2 +/- 4.1%. In rats fed a normal phosphate diet, propranolol infusion did not change phosphate delivery along the nephron. We conclude that the restoration of the phosphaturic effect of parathyroid hormone by propranolol infusion in rats deprived of phosphate for 1 day is primarily due to decreased reabsorption of phosphate by superficial loop segments, most likely the pars recta segment of the proximal tubule. PMID- 2104264 TI - Renal sodium and water handling in hypothyroid patients: the role of renal insufficiency. AB - The mechanism responsible for renal tubular abnormalities in sodium and water excretion in hypothyroid patients is poorly understood. To evaluate the possible contribution of the reduced glomerular filtration rate of hypothyroidism to these abnormalities, tubular function in hypothyroid patients was compared with that in patients with chronic renal failure and in normal subjects. The lithium clearance method and oral water loading were used to evaluate parameters of tubular sodium and water handling, respectively. The hypothyroid and the chronic renal failure patients were selected to have similar reductions in glomerular filtration rate. As compared to the normal subjects, the hypothyroid and chronic renal failure patients had a decrease in proximal sodium reabsorption and an increase in distal sodium reabsorption. The changes in tubular handling of sodium were not different in the hypothyroid and the chronic renal failure patients. Maximal urinary flow rate and free water clearances were similarly reduced in the hypothyroid patients and the chronic renal failure patients. For all subjects studied, proximal sodium reabsorption and maximal urinary volume were directly correlated with the glomerular filtration rate, and distal nephron sodium reabsorption was proportionate to delivery of sodium from the proximal tubule. The results suggest that the abnormalities in tubular sodium and water handling in hypothyroid patients are comparable to those present in other patients with a similar degree of renal insufficiency. Thus, the tubular abnormalities in hypothyroidism may be a consequence of the associated decrease in glomerular filtration rate. PMID- 2104265 TI - Proximal tubule volume regulation in hypo-osmotic media: intracellular K+, Na+, and Cl-. AB - This study sought to measure the net loss of intracellular K+, Na+, and Cl- that accompanied isosmotic cell volume regulation in hypotonic media and to determine if electrolyte loss depended on the rate at which the extracellular osmolality was reduced. Isolated nonperfused proximal S2 segments from rabbit kidney cortex were studied in vitro. Gradual lowering of osmolality from 295 to 150 mOsm/kg at a rate of 2 mOsm/kg/min did not cause an increase in tubule cell volume until the medium osmolality decreased below 190 mOsm/kg. By contrast, tubules rapidly bathed in low osmolality media exhibited classical osmometric swelling followed by incomplete volume regulatory decrease. Volume regulation associated with gradual and rapid lowering of osmolality was accompanied by the net loss of intracellular K+, Na+, and Cl- (measured by electron probe); however, the temporal pattern of electrolyte loss depended on the rate of osmotic change. With gradual lowering of osmolality, cell K+ content did not decrease significantly until osmolality was lowered below 200 mOsm/kg, whereas Cl- was lost at the 200 mOsm/kg level and below. With rapid lowering of osmolality, cell K+ content was strikingly decreased at the 200 mOsm/kg level, but Cl- did not change appreciably until osmolality was decreased to 150 mOsm/kg. Cell Na+ content decreased in hypo osmotic media, but the magnitude was relatively small. During volume regulation that accompanied either gradual or rapid lowering of medium osmolality from 295 to 150 mOsm/kg, intracellular osmolal gap, the difference between medium osmolality and the sum of intracellular concentrations of K+, Na+, and Cl- decreased 87 and 58 mOsm/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104266 TI - Use of the biopty instrument in percutaneous needle biopsy of the native kidney. PMID- 2104267 TI - Nephrology on the rise. PMID- 2104268 TI - Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. AB - This paper reviews the evidence that cytokines induce a variety of functional and structural alterations in endothelium and that cytokine-endothelial interactions play important roles in the evolution of inflammatory and immune responses. The effect of cytokines, particularly interleukin-1 and tumor necrosis factor, on leukocyte-endothelial adhesion has led to the discovery of several endothelial adhesion molecules, and the molecular and biological characteristics of these are described. Finally, the review discusses the possible contribution of cytokine induced activation to vascular injury in such pathological processes as septic shock, the Shwartzman reaction, delayed hypersensitivity, and immune-mediated vasculitis. PMID- 2104269 TI - Moderate protection of renal function and reduction of fibrosis by colchicine in a model of anti-GBM disease in the rabbit. AB - A rabbit model of renal glomerulosclerosis induced by anti-glomerular basement membrane antibody was used to determine whether colchicine would protect renal function and reduce fibrosis. Initial studies established the time course of renal function changes and fibrosis. Colchicine at a dose of 0.02 to 0.04 mg/kg per day injected ip was begun at day 4 when injury had been initiated, and the experiment was ended at day 21 when fibrotic changes were established. Colchicine significantly reduced the rise in serum creatinine (serum creatinine = 2.7 +/- 0.3 mg% in vehicle-treated animals versus 1.8 +/- 0.1 mg% in colchicine-treated animals) and interstitial fibrosis (fibrosis score = 2.6 +/- 0.2 in vehicle treated versus 1.5 +/- 0.2 in colchicine-treated animals). Colchicine treatment did not significantly affect weight, anti-guinea pig immunoglobulin level, % fibrocellular crescents formed, hydroxyproline per gram (dry weight) in tissue, or urine protein: creatine ratio. Regression analysis was performed to examine the interrelationships between variables for all animals and the effect of colchicine on pairs of variables. No clear-cut site of colchicine action could be identified. These data show that colchicine, in doses that could be used in humans, protected renal function by about 25% and reduced interstitial fibrosis in a model of severe crescentic nephritis. PMID- 2104270 TI - Mechanism of the natriuretic effect of unilateral carotid artery traction in the rat. AB - Unilateral traction on a carotid artery is known to activate the carotid baroreceptor reflex. This maneuver increases sodium excretion in a manner not completely dependent on the renal nerves, suggesting that a humoral factor(s) could be involved. We measured sodium excretion before and after unilateral carotid artery traction or sham traction in anesthetized rats and related the results to the plasma concentration of immunoreactive (IR)-gamma-melanocyte stimulating hormone (gamma-MSH), a peptide known to be natriuretic in other circumstances. In 12 rats undergoing sham traction, sodium excretion did not change and plasma IR-gamma-MSH activity at the end of the experiment was 10.5 +/- 5.4 (SD) fmol/mL. Carotid artery fraction in 20 other rats caused a transient dip in mean arterial pressure of 20.1 +/- 13.2 mm Hg, and sodium excretion increased from 746 +/- 431 to 1,739 +/- 1,436 nEq/min (P less than 0.005). Plasma IR-gamma MSH was increased to 21.1 +/- 7.1 fmol/mL (P less than 0.001 versus sham). Prior ipsilateral carotid sinus denervation markedly attenuated the carotid artery traction-related dip in blood pressure and prevented both the natriuresis and the increase in IR-gamma-MSH activity seen after this maneuver in intact rats. Pretreatment with anti-gamma-MSH antiserum also blocked the natriuretic response to carotid artery traction, despite a similar transient dip in blood pressure of 18.3 +/- 9.9 mm Hg. These observations suggest that activation of the carotid baroreceptor reflex by unilateral carotid artery traction causes natriuresis that is mediated largely by an increase in the plasma concentration of a peptide or peptides closely related to the gamma-MSH sequence. PMID- 2104271 TI - Angiotensin stimulates glucose and fluid absorption by rat proximal straight tubules. AB - I investigated the effect of angiotensin on glucose and fluid absorption by isolated, perfused rat proximal straight tubules. During the control period, tubules absorbed fluid at 0.68 +/- 0.05 nL/mm.min and glucose at 12.5 +/- 1.3 pmol/mm.min. After 10(-10) M angiotensin was added to the bath, tubules absorbed fluid at 0.82 +/- 0.06 nL/mm.min and glucose at 16.0 +/- 2.4 pmol/mm.min--a stimulation of both parameters by 30%. Time controls showed no significant change in the rate of glucose or fluid absorption. This stimulation was due to an increase in the maximum rate of transport. The maximum rate of glucose absorption with 5.5 mM in bath and perfusate increased from 14.5 +/- 1.6 pmol/mm.min to 18.5 +/- 1.4 pmol/mm.min after 10(-10) M angiotensin was added to the bath. In contrast, the Km for glucose did not change, since a solution containing 0.55 mM glucose (approximately Km) supported 63 +/- 6% of the maximum rate during the control period and 60 +/- 5% of the maximum rate after angiotensin was added to the bath. Angiotensin also had no effect on glucose permeability, which was (3.7 +/- 0.4) x 10(-6) cm/s before treatment and (3.8 +/- 0.4) x 10(-6) cm/s after treatment. From these data, it is concluded that: (1) angiotensin stimulates glucose absorption in the rat proximal straight tubule; (2) this stimulation is the result of an increase in the maximum rate of transport rather than a change in Km or permeability; and (3) stimulation of Na/glucose absorption by angiotensin accounts for a significant portion of the increase in fluid absorption caused by angiotensin. PMID- 2104272 TI - Transepithelial water permeability in an in vitro model of renal cysts. AB - Renal cysts develop from microscopic tubules and may enlarge progressively several thousandfold. Sustained epithelial proliferation, intracavitary fluid accumulation, and extracellular matrix remodeling are central elements in a multistep process that leads to the formation and enlargement of cysts. MDCK cells suspended within medium-hydrated collagen gels grow to form spherical, monolayered, fluid-filled cysts that enlarge steadily. Vasopressin and other agents that increase intracellular levels of cAMP stimulate the rate of MDCK cyst growth and net fluid/solute secretion when added to defined medium in vitro. In this model, net fluid secretion is the only means by which fluid can accumulate within the cyst cavity. We used this cyst-forming line of epithelial cells to evaluate several membrane transport properties that are important in the coupled movements of solute and water in the process of secretory fluid transport. Individual cysts were microdissected from collagen gels, held by a micropipet in a thermostated chamber, and examined at a high magnification by video microscopy. Transepithelial water flow was initiated by rapidly exchanging the bath medium with hyperosmotic solutions. Net water flux, Jv, determined from the initial rate of decrease in cyst diameter, was proportionate to the transmembrane osmotic gradient of NaCl or raffinose; the reflection coefficient for NaCl was indistinguishable from 1.0. Osmotic water permeability (cm3/cm2/osm/min x 10(-6)) was 739 +/- 99 (N = 11) in medium augmented by an NaCl concentration of 100 mosmol/kg. Hydraulic conductivity (Pt), estimated in control cysts, was 6.8 +/- 0.9 microns/s, a value similar to that of medullary and cortical thick ascending limbs of Henle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104273 TI - Growth factors in the eye. AB - In this review we report the distribution and functional significance of growth factors in the eye. Representatives of the major growth factor families are found in the eye: fibroblast growth factor, insulin and insulin-like growth factor, transforming growth factor-beta, platelet-derived growth factor, nerve growth factor, epidermal growth factor and colony-stimulating factor. There are numerous examples of their actions on ocular tissues in vitro and in some cases in vivo. The findings presented clearly illustrate that a growth factor can elicit different responses depending on the context of its action; the cell type involved, the concentration of the growth factor and the presence or absence of other growth factors can all influence the cellular response both quantitatively and qualitatively. The results of these studies in the eye are of general significance to our understanding of the role of growth factors in biological processes. PMID- 2104274 TI - Stimulators of megakaryocyte development and platelet production. AB - The range of known purified and cloned growth factors and their target cells within the megakaryocytic lineage is described. Data are reviewed outlining that megakaryocytopoiesis appears to be controlled at two levels: (i) by feedback control via circulating factors, and (ii) by factors within the marrow itself. Hypotheses are presented about the nature of thrombopoietin, its relationship to known growth factors, especially Interleukin-6 (IL-6), and the specificity of a thrombopoietic response following change in the circulating platelet mass. PMID- 2104275 TI - Introduction: endocytosis and processing of exogenous antigens. PMID- 2104276 TI - Intracellular transport and peptide binding properties of HLA class II glycoproteins. AB - Protein antigens internalized by an antigen presenting cell are degraded into peptides, a subset of which binds to the class II glycoproteins encoded by the major histocompatibility complex to form epitopes recognized by specific T cells. Current evidence suggests that the immunogenic peptides are generated in an endosomal, acidic compartment containing internalized antigen, proteinases, and exocytic class II molecules. These exocytic class II glycoproteins are associated during transport from the endoplasmic reticulum to the endosomal compartment with an additional glycoprotein, the invariant chain. Proteolytic degradation of the invariant chain in the endosomal compartment dissociates it from the class II glycoproteins, which only then acquire the capacity to bind peptides. After peptide binding occurs, the class II-peptide complexes are transported to the antigen-presenting cell surface for recognition by T cells. PMID- 2104277 TI - Transplantation tolerance with monoclonal antibodies. AB - Monoclonal antibodies (Mabs) are powerful tools for manipulating the immune system as they are capable of triggering, amplifying or suppressing immune responses. The resultant effect of monoclonal antibody (MAb) manipulation is related not only to the antigenic specificity of the antibody used, but also to its structural properties and mechanism of action. There has been much interest in using MAbs to control or regulate immune responses in vivo and they are now commonly used successfully in clinical transplantation for the treatment of graft rejection. The induction of transplantation tolerance in adult recipients is an important goal of transplantation research. The development of MAbs for immunotherapy has allowed new approaches for the induction of tolerance to vascularised organ grafts to be explored. PMID- 2104278 TI - Bone marrow transplantation as a means of inducing tolerance. AB - Successful induction of bone marrow chimerism is the most potent means of inducing specific transplantation tolerance across major histocompatibility barriers. Reliable, non-toxic methods of achieving such chimerism could obviate the need for chronic immunosuppressive therapy in clinical organ transplantation. Some novel conditioning protocols have recently been developed which permit the achievement of this goal in animal models. Recent developments have led to a greater understanding of the mechanisms leading to the induction of tolerance in each of these models. PMID- 2104279 TI - CD4 antibody therapy in systemic lupus erythematosus. AB - The emergence of monoclonal antibody technology has fostered new therapeutic strategies for people with autoimmune diseases. One of the most promising of these strategies involves the use of CD4 monoclonal antibodies, which are effective in animal models for systemic lupus erythematosus, diabetes mellitus, rheumatoid arthritis, myasthenia gravis, and multiple sclerosis. The appeal of CD4 antibodies is enhanced by several factors: (1) their effectiveness does not depend on depletion of target cells; (2) they may block the host immune response to therapy, and (3) they have been well-tolerated in preliminary human trials. The principal obstacle to the use of CD4 monoclonal antibodies stems from their adverse effects on normal immune function. PMID- 2104280 TI - The importance of non-human primates for preclinical testing of immunosuppressive monoclonal antibodies. AB - Monoclonal antibodies (MAb) specific for lymphocyte markers can be considered as very specific immunomodulating drugs for treatment of allograft rejection and autoimmune diseases. Although the selection of potentially useful specificities of MAb can be made in rodents, human specific MAb can only be evaluated in man or a closely related species in which these human specific MAb are equally reactive. Because of the restricted reactivity of human specific MAb, non-human primates are the only available species for efficacy and safety studies. This article illustrates the usefulness of such studies in rhesus monkeys and chimpanzees for the testing of T cell specific MAb and other MAb interfering with the immune response in transplantation and autoimmunity. PMID- 2104281 TI - The antiglobulin response to therapeutic antibodies. AB - The antiglobulin response to administered therapeutic monoclonal antibodies is currently one of the major limitations of antibody therapy. In the presence of a normally functioning immune system a response is inevitable after 1-2 weeks of treatment with most agents. The anti-idiotype arm of the response will inhibit the binding of antibody to target antigen, whilst both this and the anti-isotype component act to accelerate antibody clearance. Although the antiglobulin response appears to follow the rules governing immunity to soluble protein antigens the idiotypic epitopes of cell-binding antibodies seem to be particularly immunogenic. The consequence of this has been the failure to induce tolerance to therapeutic antibodies by conventional approaches and, in turn this has provided much of the stimulus to the technology of antibody 'humanisation'. It is still uncertain, however, if even a humanised antibody will remain invisible to the immune system. PMID- 2104282 TI - Humanisation of monoclonal antibodies for therapy. AB - Monoclonal antibodies are playing an increasing role in many experimental therapies. A major limitation of their use is that they are recognised by the patient as being of foreign origin and an antiglobulin response is provoked. Recombinant DNA technology offers the ability to convert these rodent antibodies into a more human form. Different degrees of humanisation can be achieved ranging from chimeric antibodies with a combination of human constant regions with rodent variable regions to fully reshaped antibodies where the variable regions are also humanised. Encouraging preliminary results have been obtained and it seems likely that these will dictate the use of humanisation as a required procedure in the therapeutic use of monoclonal antibodies. PMID- 2104283 TI - Immunotoxins and cytokine toxin fusion proteins. AB - Paul Ehrlich first suggested the simple and elegant concept of creating specific cell toxins or 'magic bullets' through the fusion of cell specific antibodies and toxins. In practice it has proven difficult to create safe and effective 'magic bullets'. In the past several years, several immunotoxins have been applied to clinical testing. These immunotoxins have been created by the biochemical coupling of cell or lineage specific monoclonal antibodies to plant toxins or fragments thereof. These immunotoxins have been used to treat bone marrow transplant recipients and patients with autoimmune disorders. In recent years, another strategy has also been pursued to create hybrid toxins. Rather than use antibodies as the targeting moiety, cytokines have been used to target a select population of cells bearing a high copy number of receptors for the specific cytokine. Rather than biochemically couple a cytokine to the toxin, the cytokine and toxin are fused by a peptide bond established via genetic engineering. A prototype IL-2 diphtheria toxin-related fusion protein is now being tested in the clinic for treatment of hematopoietic malignancies and autoimmune disorders. PMID- 2104284 TI - The dentists insurance company: the first ten years. PMID- 2104285 TI - [The efficacy of sonic and ultrasonic appliances on root canal debridement]. AB - The purpose of this study was to compare the debridement efficacy of hand, sonic (MM-3000), and ultrasonic (Cavi-Endo) appliances, utilizing the same K-type files and a constant flow irrigation system, in the mesial root canals of extracted human mandibular 1st and 2nd molars. Only those roots with a canal curvature of between 10 and 30 degrees, by Schneider's method, were used in this study. The instrumentation time per mesial root canal for each treatment group was also evaluated. Following canal preparation and histological processing, the middle and apical cross-sections were examined to determine the percentage of canal and isthmus cleanliness, and the percentage of planed canal walls in the main canal area. Statistical analysis indicated no significant difference in canal and isthmus cleanliness at the middle and apical levels. All techniques achieved a high level of canal cleanliness. However, step-back hand instrumentation had the greatest percentage of planed canal walls in the main canal area at every portion of the root. Sonic instrumentation, in this study, was significantly faster than hand instrumentation in preparing the root canal system. PMID- 2104286 TI - [An in vitro study of the antimicrobial effectiveness of ultrasonic instrumentation]. AB - Successful endodontic therapy is based upon the classic triad of diagnosis, adequate canal preparation, and obturation. Preparation for a root canal has two major components--debridement and shaping. Debridement, or cleaning, consists of removal of necrotic intracanal dentin and organic debris, and reduction of the bacteria inside the root canal. According to the research, the endontic ultrasonic system plays a valuable and significant and synergistic role in aiding the bacteriocidal mechanisms based on the cavitation and acoustic streaming effect. The purpose of this study was to compare the antimicrobial effectiveness of two newly developed endodontic ultrasonic devices and the conventional hand filing techniques. Eighty single root canal teeth with deep caries or apical lesions were selected and evenly divided into 4 groups. The root canals were prepared using conventional hand filing or one of two newly developed ultrasonic filing systems, ENAC and CAVI-ENDO. The contents of the root canals before and after debridement were cultured in a thioglycolate culture tube. The results showed that in the ultrasonically prepared specimens irrigated with a normal saline solution, the microbial culture numbers were significantly reduced and obviously different from those prepared by the hand instrumentation technique. The above mentioned differences were statistically significant at the level of p less than 0.05 by the McNemar test and Chi-square test. PMID- 2104287 TI - Assessment of periodontal disease in an adult population survey in Taipei city using CPITN and GPM/T indices. AB - The community periodontal index of treatment needs (CPITN) has been recommended for epidemiological surveys of periodontal status and treatment needs. The prevalence of gingivitis, periodontitis and missing teeth in a study population has been determined using the CPITN and GPM/T (gingivitis: periodontitis: missing teeth) indices. In this study, a survey of periodontal disease was performed among the adult population of Taipei City using the CPITN index. A total of 673 dentated persons (male 339, 50.4%; female 334, 49.6%) were examined and surveyed. Data were then divided into five age groups, 15-19, 20-29, 30-44, 45-64 and 64+. The prevalence of periodontal disease was analyzed using the percentage or sextant from all teeth. Treatment needs were determined by the worst periodontal score per sextant. It was found that about 91% of subjects suffered from various degrees of periodontal disease in at least one tooth. Gingivitis and periodontitis were 86.9% and 33%, respectively. Among them 48.9% had missing teeth. The prevalence of periodontitis and missing teeth increased with age. Most of them involved oral hygiene instruction and scaling. About 11.0% of the subjects needed periodontal surgery. Higher proportions of attachment loss with gingival recession caused by destructive periodontal disease were found in older persons who did not require periodontal surgery. It was concluded that endemic gingivitis and calculus, a moderate prevalence of shallow pockets and a low prevalence of deep pockets were observed among adults in this group in Taipei City and that the CPITN is a practical epidemiological and public health method for screening the periodontal status and treatment needs of a population. PMID- 2104288 TI - [Effects of subgingival antimicrobial irrigation in chronic periodontitis- clinical observation]. AB - One week prior to the establishment of baseline records, 144 sites with a probing pocket depth of 5-7 mm in 13 periodontitis patients were treated with plaque control and root planning. Sites with periodontitis involvement in each patient were divided, by split mouth design, into 4 quadrants. Each quadrant was irrigated subgingivally with either 0.05% metronidazole or 0.05% ornidazole, or 0.2% chorhexidine, or 0.9% normal saline (control) once every 2-3 days for 4 weeks. The plaque index, sulcus bleeding index, probable pocket depth and gingival index were assessed at the baseline and at 4 weeks, 8 weeks and 12 weeks following initial preparation. All 4 clinical parameters in the ornidazole treated group showed significant improvement as compared with baseline values, but the improvements were not maintained to the end of the study. Except for improvement in the sulcus bleeding index and the gingival index in the ornidazole group, which was superior to that of the metronidazole group at the 4th week, there were no significant differences in other parameters between the ornidazole, metronidazole and chlorhexidine groups at the irrigation sites. From these data we can tentatively conclude that subgingival irrigation with ornidazole in deep pockets is more effective than metronidazole or chlorhexidine in nonsurgical periodontal therapy. PMID- 2104289 TI - [Health problems of the stomatognathic system in the Polish population covered by stomatological health care. Place of residence and work]. AB - The condition of the stomatognathic system was studied in 5682 adult patients attending stomatological care services in regional outpatient clinics, health service centres, and industrial health service units in 6 provinces. Most frequently, the patients came to these services with emergency symptoms. Poor state of teeth was observed in all these service units, but the worst oral hygiene and the highest percent of parodontal diseases were found in industrial health service institutions. In this group tooth loss was most frequent. These results indicate that the stomatological health care in industrial service units despite an above average equipment of dental care rooms, better availability of dental care, and sufficient staffing is not better than in the stomatological care units available to the general population. PMID- 2104290 TI - [Comparative investigations on toothpastes]. AB - A comparative study was carried out of the clinical usefulness and properties of two types (differing in the type of chalk used) of the following toothpastes: Nivea, Herbena, Salodent and four various Fluorodent toothpastes (differing in the type of calcium carbonate and thickener). The study was carried out on 100 students of the first classes of the Economics College in Poznan. The obtained results of clinical investigations justify the replacement (in part at least) in the production of toothpastes of the imported chalk Socal with Polish chalk from Janikowo. PMID- 2104291 TI - [Effect of chemical composition of powder and mercury content on the development of phase gamma-2 in amalgam structure]. AB - The purpose of the reported model study was determination of the effect of the content of mercury differentiated with respect to the preparation procedure and application of amalgam technique (condensation) in the tissue defect on the chemical composition (phasic) of this type of filling using three various materials: Stabil-B, Amalcap-Non-Gamma and Amalcap. Stabil-B had a generally higher content of mercury, and a lower content of this metal was found in Amalcap and Amalcap-Non-Gamma 2. The lowest amount of phase gamma 2 was found in Amalcap Non-Gamma-2 and the lowest in Stabil-B. PMID- 2104292 TI - [Assessment of motivating factors for conservative treatment of teeth by stomatological students]. AB - On the basis of responses to an inquiry provided by patients the motivating factors were assessed which induced the patients to undergo dental treatment provided by students of the stomatological faculty. The main motivating factors were: careful performing of procedures, good results of treatment, short waiting time for visit. PMID- 2104294 TI - [Labial rubor reconstruction with a flap from the tongue]. AB - The evolution of the method used for reconstruction of labial rubor is described laying stress on the use of tongue tissue. Two cases are reported for illustration. PMID- 2104293 TI - [Disturbances of the development of enamel-forming organ as an etiological factor in pulp diseases]. AB - On the basis of a literature survey the author discusses the so called everted odontoma, a developmental anomaly of dental tissues which may lead to diseases of the pulp and periapical tissues. The method is described of treatment of periapical inflammatory conditions which may be due to these anomalies. PMID- 2104295 TI - [AIDS primer for stomatologists on the basis of a literature survey]. AB - On the basis of a literature survey, mainly of two American periodicals from 1987 the epidemiology, manifestations and treatment of AIDS patients are discussed with particular reference to the changes development on oral mucosa and to the treatment of these changes. The knowledge, attitudes and behaviour of stomatologists towards the risk-group patients and AIDS patients are discussed on the basis of the results of an inquiry with participation of 541 dentists from California. The degree of risk of infection of stomatologists and medical personnel with HIV during treatment of AIDS patients is discussed for protection of the dentists and auxiliary personnel the use is recommended of rubber gloves, masks and protective goggles during work. It is thought generally in the light of our knowledge up to now that the possibility of HIV infection during the work of dentists is low, lower than in the case of hepatitis virus B infection if the basic hygiene principles and caution are observed. PMID- 2104296 TI - [Active plate in preoperative treatment of infants with primary and secondary palatal clefts]. AB - The study deals with trials of early maxillo-orthopaedic treatment of children born with cleft anomalies of the palate. In infants aged 1-2 weeks with unilateral or bilateral clefts of the primary and secondary palate with high grade maxillary deformity active upper plate was used since the first labial operation at the age of 6-7 months. The obtained improvement in the mutual relationships of the cleft parts of the maxilla, the semicircular shape of the maxillary alveolar process and restoration of normal functions of sucking and swallowing ensure normal development of occlusion and function of the stomatognathic system. PMID- 2104297 TI - [Some considerations on the failures in malocclusion treatment]. AB - In the interpretation of the author failures in the treatment of malocclusion include lack of achieving of the planned change of the primary occlusion shape despite good prognosis. The failures may be divided into: persistence of the initial morphological and functional conditions throughout the whole time of treatment, return on the initial occlusion shape after some time despite obtaining of apparent success of treatment. The appearance during the treatment of additional pathological factors, the manifestation of new pathological features in juvenile life period despite reshaping of occlusion in childhood according to treatment plan, increased mobility of teeth, hypertrophy, atrophy or decubitus ulcers of the oral mucosa and development of necrotic foci in the periosteum and pulp necrosis. Among the causes of failures in malocclusion treatment the author gives attention to the activities of the dentist and the attitude of the patient towards the treatment. Attention is called also to difficulties in collection of documentation of failures in the treatment of malocclusion. It is suggested that even fragmentary observations could help in improvement of therapeutic methods. PMID- 2104298 TI - [Methods of treatment of preschool children used in the orthodontics department, Institute of Stomatology, Medical Academy in Warsaw]. AB - The reported analysis was based on 288 clinical cards of patients aged 2 to 6 years, admitted for treatment in the years 1980-1985. The greatest group was that of children aged 3 years (28%), followed by those aged 6 years (25%). Abnormalities from the group of distocclusion prevailed (28%), followed by teeth abnormalities (26%), and cross-bite (16%). In 165 cases functional apparatus was used initially, in 66 cases Schwarz or Adams plates, in 31 cases dental prostheses, and in 22 cases chin sling. Four cases were observed after removal of malocclusion cause. Besides treatment with removable devices myotherapy and spatula exercises were used. PMID- 2104299 TI - [Teeth condition in children aged 7 years in Warsaw and the province of Warsaw]. AB - Teeth were examined in 180 children aged 7 years of either sex in three randomly selected regions: Warsaw, Sulejowek and Wiazowna community by the routine method in school stomatological offices. The assessment of teeth was done according to the WHO principles. In the studied population 85.3% erupted permanent molars, 71.1% medial incisors, and 29.2% lateral incisors were found. No significant differences were found in the per cent of erupted permanent teeth between these three regions, but the proportion of erupted teeth was greater in girls than boys. The prevalence of caries in the permanent teeth in this population was 25%, and again no difference of this prevalence was found between these three regions, but in girls this prevalence was greater than in boys. The DMF index was not different in these regions, but in girls it was twice that in boys (0.6 vs 0.3). PMID- 2104301 TI - [Microhardness of amalgams Stabil B and Amalcap]. AB - The microhardness of the amalgams Stabil B and Amalcap was determined and compared. Samples of the Stabil B amalgam were divided into three groups depending on the amount of mercury and mode of preparation. The experiment showed that Stabil B amalgam prepared in the proportion of 5 weight parts of filings and 6 parts of mercury had a final microhardness of 145.4 kG/m2, similar to that of Amalcap which was 155.1 kG/mm2. Stabil B amalgam prepared manually had a significantly lower microhardness which was 119.6 kG/mm2 for the 5:6 proportion and 103.9 kG/mm2 for the 5:7 proportion. PMID- 2104300 TI - [Temporomandibular joint dysfunction and its relations to prosthetic needs]. AB - As part of the programme of the Ministry of Health and Social Care 180 subjects aged 35-44 years living in Cracow, Wieliczka and its environs were studied. They were divided into 6 groups of 30 subjects in each. Temporomandibular joint dysfunction was found in 44.44% of the studied material, it was slightly more frequent in women (47.77%). The frequency was greater in the subjects living in villages. A comparison of the studied groups failed to show any statistical significance of the differences. In the analysis of temporomandibular joint dysfunction in relation to occupation it was revealed that it was most frequent in qualified workers. The need for prosthetic treatment was estimated in subjects with this dysfunction and this need was recognized in 83.75% of these subjects. PMID- 2104302 TI - [Clinical pattern of secondary dental caries in relation to tissue defect class and type of filling material]. AB - The purpose of the study was assessment of the development of secondary caries in relation to filling type in various classes of carietic dental tissue defects. The study was carried out in 320 patients aged 16 to 55 years and 3884 teeth were examined. Out of this material 2423 teeth were filled: with amalgam--853, with silica cement--1197, with composites--373. Secondary caries was found in 1341 teeth (56.34%). In teeth filled with amalgam in classes I and II of carietic defect in women secondary caries was noted in 27.26% and 47.73% of cases respectively. In case of composite filling secondary caries was found in 72.12% and 81.82% of fillings. In class III of carietic defects in women with fillings with composite materials secondary caries developed in 48.8%, and after filling with silica preparations in 55%. In class IV secondary caries was present at 45% of composite fillings and 77.78% of silica cement fillings. In class V secondary caries was found at 11.42% of amalgam fillings and 36.67% of composite fillings, and in 45% at silica cement fillings. Similar values were found in men. PMID- 2104303 TI - [The habit of black lacquering of teeth and dental caries]. AB - The habit of applying black lacquer to teeth is widespread in Vietnam. Observations are reported on its effect on the incidence of dental caries and its usefulness in caries treatment. PMID- 2104304 TI - [Localization of retained teeth in radiogram]. AB - The purpose of the study was evaluation of various possibilities of localization of retained teeth. The study was carried out on 86 patients referred to the Department of Conservative Stomatology, Institute of Stomatology Medical Academy in Lublin. Retained teeth were discovered in them accidentally or in examinations for various symptoms. On the basis of history data, clinical examination and radiological findings the following localization of retained teeth was recognized: 1) lateral or anterior part of the mandible, 2) lateral or anterior part of the maxilla, 3) maxillary sinus or its vicinity, 4) ascending ramus or condular process, 5) vicinity of the lower orbital margin and piriform fossa. PMID- 2104305 TI - [Radiocinematographic assessment of deglutition after surgical treatment for oral and maxillary neoplasms]. AB - The authors report the results of radiocinematographic examinations of 98 patients operated on for oral and maxillary neoplasms with analysis of the disturbances of various phases of deglutition in relation to the site and extent of the operation. Leakage into lower respiratory tract is discussed. Extensive operations in the mouth and on the lower and upper jaws were found to cause disturbances of both deglutition phases, and retention of contrast in postoperative tissue defects limitation of the movements of various anatomical structures were the most frequent disturbances of deglutition. PMID- 2104306 TI - [Surgical treatment of infraorbital neuralgia (exeresis) with description of an original method]. PMID- 2104307 TI - [A case of maxillary Schneider's papilloma]. AB - A very rare case of bilateral maxillary Schneider's papilloma is described in a patient aged 61 years treated with cytostatics and observed during 8 years. The neoplasm destroyed the maxilla, infiltrated the nasal cavity, ethmoid bone, cheeks, lower eyelid, temple, and facial nerve rami on the left side, and began penetrating into the left orbit and right sphenopalatine fossa. The general condition of the patient was good. PMID- 2104308 TI - [Modified Klammt apparatus for treatment of stomatognathic abnormalities in preschool children]. AB - Klammt apparatus was modified adapting it for treatment of occlusal abnormalities in milk teeth. The resting and functional positions of the tongue were used for this aim through appropriate directing of its action in the apparatus for widening of anterior parts of dental arches. The usefulness of the modified apparatus in the treatment of stomatognathic system abnormalities was assessed in 90 preschool children with malocclusions of crossbite type, open bite, anterocclusion and posterocclusion. The control group comprised 90 preschool children with similar abnormalities treated with monoblock. The results were significantly better after treatment with the modified Klammt apparatus, the dental arches were rapidly widened, therapeutic effects were better, rehabilitation of the muscles was more complete. Using the modified Klammt apparatus the children could easily speak, and thus the apparatus could be used longer than monoblocks which had a positive effect on the final therapeutic results in these cases. PMID- 2104309 TI - [Reactions of school children to the appearance of teeth]. AB - Using a questionnaire the author collected data from 170 school children aged 9 to 12 years. In 70% the children came from the families of intelligentsia and in 30% from working classes. The responses to the questionnaire made possible establishing the number of children given nicknames, establishing the cause of the nickname and reaction to it. The own opinion of own appearance was presented by the children who were asked to answer the questions about the physical feature of own body with which they were dissatisfied and which they would like to change. Nicknames of various origin had 72.12% of children. The most frequent were distortions of the first name or family name. No nickname referred to the appearance of teeth. In 81.75% of cases the children were not offended by the nicknames, but nicknames referring to physical features were usually disliked. In self-opinions on own appearance the children mentioned teeth as a feature which they would like to change as first. PMID- 2104310 TI - [On medical chambers]. AB - The author describes the history of Medical Chambers in Poland. The first organization bonding physicians was founded in Gdansk at the beginning of the 17th century--the Collegium Medicorum Gedanensis. This Collegium was later on recognized as the first Medical Chamber in Poland. The author describes the foundation of Medical Chambers in the Polish territories under the Austrian and Prussian occupation, and the organization and activities of Medical Chambers between world wars. In connection with the present restructuring of the Medical Chambers the author points out that in their organization and programming historical experiences should be utilized, but warns against mechanical repetition of these experiences since the present goals and other conditions are different for the activities of these chambers. PMID- 2104311 TI - [Modern methods of caries treatment]. AB - Methods of treatment of advanced caries with loss of hard dental tissues are reviewed discerning especially six such methods: 1) adhesive filling using composites, 2) filling with composites resistant to mechanical trauma, 3) filling made of conventional composites, and polyacrylate cements, 4) conventional filling with silicon cements, 5) conventional filling with silver amalgam, 6) filling with inserts. The author points out that as yet there is not plastic material better than amalgam for filling defects of class I, II and V where aesthetic requirements are not important. PMID- 2104312 TI - [Enzymatic tests for alkaline and acid phosphatase in gingival tissues in workers of the Chelm Cement Plant]. AB - Using histochemical methods the activity of alkaline and acid phosphatase was determined in the gingivae of 38 workers aged from 26 to 59 years employed in work with greatest exposure to dust. The control group comprised 11 men aged 23 to 49 years living in Chelm or in its vicinity, not exposed to cement dust. The activity of alkaline phosphatase in the group with exposure and with deep gingivitis of lower intensity was very high, while it was lower in the group with highest intensity of the inflammatory process. The activity of acid phosphatase increased with increasing intensity of pathological changes. PMID- 2104313 TI - [Clinical assessment of the reconstruction of hard dental tissues by means of Evicrol and Izofill in children]. AB - For the reconstruction of hard dental tissues in children composites Evicrol (Spofa) and Izofill (Vivadent) were used. The fillings were controlled after 24 months assessing the response of pulp, resistance of the reconstruction, marginal contact, colour and lustre. The control of the fillings showed that both materials could be used for reconstruction of hard dental tissues. In the clinical assessment Izofill had better features, preserving better durability of the reconstruction, marginal contact and colour. PMID- 2104314 TI - [Quantitative and qualitative characteristics of the bacterial flora of saliva and dental plaque in artificially fed children]. AB - Stomatological and bacteriological studies were carried out in 66 children aged 1 5 years divided into two groups: I--without caries, II--with carietic lesions typical of the so called "bottle caries", that is with carietic defects on the vestibular surfaces of upper incisors and on masticating surfaces of first molars. No differences of qualitative character were found in the bacterial flora of the saliva and the dental plaques in children with "bottle caries" in relation to those without caries. A significant correlation was noted between the quantity of S. mutans and Lactobacillus in the saliva or dental plaque and the intensity of caries. These results confirm the suggestions of other authors that Str. mutans plays an important role in caries and that it is the prevailing species among acid-producing flora in children with bottle caries. PMID- 2104315 TI - [Evaluation of caries prevalence in children and adolescents in Zabrze subjected to planned stomatological care]. AB - In a group of 923 children aged 8 to 15 years (475 girls and 448 boys) caries was found in 80.61%. The intensity of the carietic process (DMF) was for the whole group 3.08 teeth. The study demonstrated increasing prevalence of caries with age. The intensit and the prevalence of caries were greater in girls than in boys. The analysis of the components of the DMF index showed a considerably large proportion of teeth with active caries with a low proportion of filled and removed teeth. The mean D index in the whole group was 2.09, in girls it was 2.22, in boys 1.93. The mean number of filled teeth was low: 0.91 for all children, 1.09 for girls, and 0.72 for boys. In the studied population the characteristic age, that is reaching of equal DMF values for the maxilla and mandible, was at the end of the 12th year of life and earlier in girls. Moreover, it was found that the intensity of caries was greatest in molar teeth and lowest in canine teeth. This was due, among others, to the condition of sixth teeth which was unsatisfactory. The mean DMF of the first permanent molars was 2.28 for the whole group, 2.46 for girls and 2.09 (teeth) for boys. PMID- 2104316 TI - [Oral condition in children and adolescents exposed to sociopathies]. AB - The children and adolescents with a likelihood of developing sociopathies come mainly from the families of alcoholics and lowest groups of the society, and they account for a large percent of the so called social orphans. The conditions of life in their parental homes expose them to continuous stress which is not without effect on the developing stomatognathic system. The stomatological examination in this study was carried out in 105 children of preschool and school age in the Emergency Social Care units, Police Children's Stations and Hostel for the Minors. In the examination of the stomatognathic system the state was evaluated of the teeth and parodontium, the need for treatment, a and the anatomical conditions of the oral vestibulum. In the studied children and adolescents exposed to contact with sociopathies the state of teeth and parodontium was worse than in their peers from normal families. Thus their needs for treatment were greater. Occlusal abnormalities and parafunctions were more frequent than in controls. Disturbances of enamel structure were much less frequent. PMID- 2104317 TI - [Different mechanisms of fluoride binding by bones and teeth]. AB - Dental and skeletal hydroxyapatite have a high affinity to fluorine. For demonstration of possible difference in fluorine binding by teeth and bones fluorides were determined in teeth buds, milk teeth and femur of human fetuses. A relatively stable content of fluorides was demonstrated in teeth buds and in milk teeth of children In the fetal bone the level of fluoride was lowest, but according to literature data, it rises with age. The observed differences in fluoride levels may be due to different physicochemical properties of dental hydroxyapatite and bone hydroxyapatite, or to different regulation of fluoride binding. PMID- 2104318 TI - [Ligature binding by Risdon's method]. AB - Classical and modified Risdon's binding was applied in 165 patients with jaw injuries as permanent immobilization. The method was applied in 79 outpatients and 86 inpatients in cases of: 1) isolated mandibular fractures in 124 cases (without displacement in 88 and with displacement in 36), 2/15 cases of dislocated teeth, 3) 10 cases of alveolar process fractures, 4) 6 cases of maxilla fracture, 5) 2 cases of tooth reimplantation, 6) 8 cases of osteosynthesis. This immobilization was done only in patients with preserved permanent teeth or with only some teeth missing, in recent fractures without displacement or with only slight displacement. In 162 cases (99.8%) good reduction and stabilization with union of fracture was achieved. The method with its modification is highly suitable for the treatment of isolated mandibular fractures as a simple, easy and effective method when the cases are properly qualified. PMID- 2104319 TI - [Orthodontic management in cases of maxillary fused teeth]. AB - In the light of own cases the authors present congenital dental anomalies--fused teeth. This abnormality was present in three boys aged 9, 10, 11 years, involving upper permanent incisors. In all these cases extraction was done for orthodontic indications. Various methods of management are discussed in these often difficult cases, and the results of orthodontic treatment. PMID- 2104320 TI - [Lower hinge plate device with asymmetric action]. PMID- 2104321 TI - [Qualitative and quantitative assessment of occlusion in a selected group of children]. AB - The occlusion of 102 children from the Province of Krosno was assessed by means of the diagnostic principles of Orlik-Grzybowska and a scoring system of Masztalerz. The complex of morphological-functional features proper for age was found in 30.39% of children, while malocclusion was diagnosed in 69.61% of them. On the other hand, in the point score evaluation normal occlusion was found in only one child. This indicates a lower sensitivity of the qualitative assessment of occlusion. In the studied group of children posterior malocclusions were most frequent--27.45%, and crowding was second in frequency--26.47%. The occurrence of malocclusion was increasing, from 57.5% in 1966 to 69.61% in the present study which points to a need for extending the orthodontic health care in prevention and treatment even in regions with good climatic conditions. PMID- 2104322 TI - [Articulation and nasalization in palatal cleft]. AB - The author studied 189 patients after operations for cleft palate who had not had earlier logopedic rehabilitation. The range of disturbances was presented as a sum of abnormal articulations against a background of functional disturbances of various degree. Preponderance of articulation disturbances was noted--84.7% in relation to nasalization--75.1%. Patients with moderate and high-grade nasalization achieved evidently worse results of speech rehabilitation and had a much smaller possibility of autocorrection in relation to those with--out impairing nasalization. Moreover, articulation changes were found in patients without nasalization and with low-grade nasalization, which suggests persistence of habits, and the need for early exercises to prevent the formation of harmful compensations. PMID- 2104323 TI - [Late results of treatment of deep periodontopathies with plastic operations of the gingiva and alveolar process]. AB - The effect was assessed of plastic operations on the gingiva and alveolar process by a method similar to the Cieszynski-Widman-Neumann technique on the condition of the parodontium in 133 patients aged from 13 to 58 years. For evaluation of the condition of parodontium Kotzschke's index and Engelberger's et al. radiological index were used and the oral vestibule was measured. Control examinations were done 2-15 years after the treatment. After surgical treatment reduction of the pathological gingival pouches was observed in 88.7% of the patients, while gingivitis was alleviated in 85.1% of cases. Kotzschke's periodontopathy index was improved in 86.5% of cases, and dental mobility decreased in 64.6% of cases. The radiological index demonstrated regeneration of bone in 60.1% of the surgically treated cases in the range from 1.0 to 3.5%, and in 4.5% of cases bone atrophy was stopped. However, denudation of dental roots increased in 66.1% of cases. After surgical treatment narrowing of the width of the alveolar gingiva was by 0.4 mm in 77.5%, the depth of the vestibule was reduced by 0.3 mm in 57.5% of cases, and the "pull syndrome" manifested itself in only 9.8% of cases. PMID- 2104324 TI - [Clinical assessment of toothpaste with vitamin A in patients with periodontal diseases]. AB - The effectiveness was assessed of a toothpaste with vitamin A and a toothpaste without this vitamin in the treatment of parodontal disease. Significant differences in the therapeutic action of both pastes were observed in patients with superficial inflammatory periodontopathy. The toothpaste with vitamin A had a more favourable effect. PMID- 2104325 TI - [Occurrence of defects of connective tissue attachment in adults with periodontal diseases]. AB - The position of the connective tissue attachment was determined by Ramfjord's method in subjects aged 20-29 and 40-49 years. In the determination four surfaces of all remaining incisors, canines, and premolars were considered. A defect of the connective tissue attachment was found in about 95% of the analysed dental surfaces in subjects aged 40-49 years. The frequency of occurrence of these defects varied depending on the type dental surface. PMID- 2104326 TI - [Results of treatment of upper gingiva and palate carcinomas]. AB - From 1981 to 1986 in the Department of Maxillofacial Surgery, Institute of Stomatology, Medical Academy in Warsaw 85 patients were treated for carcinoma of the upper gingiva and palate. The follow-up of the patients after treatment was from 3 to 7 years. The obtained results of the treatment were analysed depending on the degree of differentiation of neoplasms and their biological aggressiveness and the therapeutic method used. It was found that the results of the treatment of upper gingiva carcinoma were not satisfactory. The best results were obtained using surgical treatment followed by radiotherapy. A positive result of the treatment without symptoms of recurrence was achieved in 21 cases (24.7%). PMID- 2104327 TI - [Comparison of the effectiveness of conventional methods of radiological examinations and computed tomography in the diagnosis of lower gingiva tumours]. AB - In 22 patients aged 34 to 87 years treated in the Department of Maxillofacial Surgery, Institute of Stomatology, Medical Academy in Warsaw for malignant tumours of the lower gingiva the usefulness was assessed of the conventional radiological methods and computed tomography for the evaluation of malignant infiltrations. Computed tomography was found to be an auxiliary radiological method determining best the morphology and syntopy of malignant neoplasms of the lower gingiva infiltrating the soft tissues of the oral floor. PMID- 2104328 TI - [The effectiveness of selected surgical methods in the treatment of zygomatico maxillary fractures]. AB - In a period of 3 years, from 1984 to 1986 in the Department of Maxillofacial Surgery, Institute of Stomatology, Medical Academy in Warsaw 442 patients were treated for zygomatico-maxillary fractures, in 101 cases the treatment was conservative, and 341 were treated surgically by various operative methods. The aim of the study was assessment of late effectiveness of the surgical methods used most frequently in zygomatico-maxillary fractures with reposition of skeletal fragments either with one-pronged hook introduced percutaneously or from the side of the lumen of the maxillary sinus. The criterion of effectiveness of both methods was accepted to be functional assessment of the visual system and the stomatognathic system, and the condition of sensory function in the area of innervation by the suborbital nerve. Control examinations were done 2-5 years after operations confirming the both methods were successful in 90% of the treated group. A more detailed analysis of these methods is not possible since the qualification for these operations differentiated essentially both groups of patients. PMID- 2104329 TI - [Late results of treatment of maxillary fractures]. AB - In the period of 3 years, from 1984 to 1986 in the Department of Maxillofacial Surgery, Institute of Stomatology, Medical Academy in Warsaw 230 patients were treated for maxillary fractures. Late results of this treatment were assessed in 102 patients coming for control examinations in 1988. In the assessment of the therapeutic results the following features were considered: facial symmetry, proportions of three facial segments, functions of the visual system and stomatognathic system, nasal patency, and sensory disturbances in the area innervated by the infraorbital nerves. On the basis of this late assessment of the results of treatment of these fractures it was found that the definite morphological-functional and aesthetic results were unsatisfactory in cases of Le Fort III and II type maxillary fractures. This points out that the therapeutic methods used as yet are not sufficiently satisfactory and other methods should be evolved. PMID- 2104330 TI - [Analysis of surgical-orthopaedic treatment of mandibular fractures in patients treated in the period 1984-1986]. AB - During 3 years 1246 patients were treated for mandibular fractures, 828 of them were treated by conservative-orthopaedic methods while in 418 patients the displaced mandibular fragments were reduced and fixed surgically using various methods. The purpose of the assessment was a group of 319 patients in whom the fragments were reduced and fixed with ossous sutures. A good result of treatment was achieved after this operation in 291 cases (91.2%). In 28 patients (8.8%) postoperative complications developed requiring reoperation. PMID- 2104331 TI - [Late results of treatment of mandibular fractures]. AB - In a group of 1246 patients treated in the Department of Maxillofacial Surgery Institute of Stomatology, Medical Academy in Warsaw, in a period of 3 years (1984 1986) late results of treatment of mandibular fractures were assessed. In the assessment the range of mandible abduction, function of temporomandibular joints, occlusal abnormalities, the sensory function in the area innervated by the mental nerves and the condition of posttraumatic scars changing the morphology and aesthetic appearance of the face were considered. Limitation of mandibular abduction after treatment was found in 39 cases. Functional disturbances of temporomandibular joints developed in 58 cases, and various occlusal complications were found in 130 out of 1246 patients. In 56 patients various sensory loss was noted in the innervation area of the mental nerves. Posttraumatic scars in 89 patients affected in various degree facial morphology and aesthetic appearance. PMID- 2104332 TI - [Craniopantograph--an instrument for determination of orbit shape]. AB - The authors describe the structure of principles of function of a measuring recording instruments, so called craniopantograph. The instrument of own design serves for examination of the spatial variability of the orbit. The obtained measurements of the internal shape of the orbit can be processed later by microcomputer technique. For construction of craniopantograph the principles of function of two typical instruments--craniometer and pantograph were used. PMID- 2104333 TI - [The method of examination and clinical application of magnetic nuclear resonance in the diagnosis of facial skeleton]. AB - On the basis of modern literature the present state of knowledge on MNR and the diagnostic effectiveness of this method in various diseases of the facial skeleton are discussed. The diagnostic effectiveness of MNR is compared to that of computed tomography. PMID- 2104334 TI - [Health problems of the stomatognathic system in the Polish population attending dental health service offices]. AB - The results of the reported study showed considerable differences in the causes of attending dental health service offices, and differences in the health state of the stomatognathic system in the studied populations in certain provinces. Not always these differences were due to the index of dental health service availability. The index of this availability had a significant effect on the results of the therapeutic activity of dentists, and was unrelated to the results of prophylactic activities. Usually more teeth with active caries and more missing teeth were in the provinces with prevalence of peasant population. At the same time these provinces had a lower per cent of subjects with unfilled gaps in teeth. High per cent of studied subjects with missing teeth, usually not replaced or only partially reconstructed can be explained by very low attendance of patients to prosthetic laboratories. PMID- 2104335 TI - [Studies on the occurrence of systemic manifestations during first eruption of teeth in children]. AB - The aim of the study was establishing whether systemic symptoms and signs appearing in children during first eruption of teeth are connected with this process, and what is the correlation between the studied features and eruption of individual milk teeth. The study involved 55 generally healthy infants aged 3-4 months, and the observation was continued up to the age of 36 months. The study on the development of teeth was carried out in two Regional Paediatric Dental Clinics in Warsaw, at 6-week intervals in the first year of life, and at 10-week intervals in the 2nd and 3rd years. The systemic symptoms and signs were recorded by mothers, and the obtained data were stored on computer cards. The results were subjected to statistical analysis considering finally these systemic manifestations which were present in at least 25% of children. The manifestations connected with teeth eruption included: profuse salivation, biting of hard, things, restlessness, appetite loss and sleep disturbances. These symptoms were most pronounced at the time of milk incisors eruption, less evident during eruption of first molars, and were absent during eruption of second molars. Canine teeth eruption was connected particularly with restlessness and sleep disturbances. Such signs as raised body temperature, skin changes, gastrointestinal disturbances were only weakly connected with teeth eruption. PMID- 2104336 TI - [The condition of teeth and the need for teeth treatment in drug addicts]. AB - The condition of teeth was studied in 30 drug addicts aged 21-34 years (drug addiction duration 3-16 years) comparing the results with those obtained in a similar group of 30 age-matched subjects without drug addiction. The needs for stomatological treatment were determined also. It was found that drug addicts had twice the number of teeth with active caries and missing teeth, and four times less filled teeth as compared with controls. Most drug addicts had lost 45-100% chewing ability, and loss of teeth included all anatomical groups. The mean number of teeth requiring treatment per one addict was 8, and 2.8 teeth required removal. Only 3 addicts were not in need of prosthetic treatment, the remaining ones (90%) should have been given permanent of removable replacements (including complete denture). Drug addiction was found to produce intensification of caries and mutilation of the stomatognathic system. PMID- 2104337 TI - [Study on the content of certain elements in retained teeth]. AB - The content of calcium, phosphorus.potassium and zinc was determined in 21 retained canine teeth and in a control group of canine teeth erupted completely. In the measurement the method of X-ray fluorescence was used. The obtained results were subjected to statistical analysis. In relation to control canines the retained teeth contained significantly more calcium and phosphorus and significantly less potassium. No significant differences were found in zinc content. PMID- 2104338 TI - [Resorption of roots of milk teeth treated by pulp amputation using formocresol]. AB - Histological examination was carried out of milk molars involved by physiological or pathological resorption, i.e. accelerated, during treatment of pulp diseases by amputation using formocresol, and delayed in case of persisting milk teeth. The results showed that the histological pattern of accelerated resorption due to formocresol was not different from physiological resorption. Delayed resorption was associated with an evident repairing reaction in the resorption sinuses. PMID- 2104339 TI - [Clinical and radiological assessment of the results of using grafts of allogenic lyophilized spongy bone for filling of large postoperative jaw bone defects]. AB - The authors describe the method of filling large bone defects in the maxilla and mandible with blocks of allogenic spongy bone enriched with biologically active substances. This method was used during 2 years in 21 cases with good results. Two-year clinical and radiological observations are reported, with detailed radiological documentation of 3 cases. PMID- 2104340 TI - [Evaluation of the effects of various fluoride concentrations in drinking water and atmospheric air on permanent teeth eruption in children aged 12 years]. AB - Dental age was evaluated in 382 children aged 12 +/- 6 years in four Silesian localities differing in the content of fluorine in drinking water and air: in Milicz--without fluoride, in Wroclaw where artificial Fluoridation of drinking water is conducted to levels regarded as optimal--from 0.8 to 1.2 mg/l, in Gryfow where the mean annual pollution of atmospheric air with fluorides was from 0.044 to 0.059 mg/m3 in Nysa where drinking water contains an excess of fluorides 4.0 to 7.0 mg/l. In the light of these studies fluoride was found to retard teeth age. The greater dose of fluorine is taken up by the organism in the period of development the longer is the retardation of dental age. PMID- 2104341 TI - [Elastic traction for correctly situating rotated teeth in patients with cleft palate]. AB - In 15 patients with cleft palate rubber traction was used on 20 rotated permanent incisors placing the traction bands between clasps made of composites on the teeth and orthodontic devices. The method was suitable for correction of the position of rotated incisors in these children. PMID- 2104342 TI - [The condition of periodontium in children treated with removable orthodontic devices]. AB - The purpose of the study was establishing whether, and if so, which regulatory devices traumatize the parodontal tissues. Clinical examination was done in 60 children treated with functional devices and 20 with mechanical devices before the treatment and 3 to 5 months after treatment beginning. The condition of the parodontium was assessed by means of the gingival index and the periodontal index of Russell. Oral hygiene was assessed using the plaque index. In the light of the obtained results it may be said that removable functional and mechanical devices for teeth regulation caused no pathological changes in parodontal tissues in children aged 7-10 years. PMID- 2104343 TI - [Health problems of the stomatognathic system in the Polish population receiving stomatological care. Health needs and the possibilities of their realization]. AB - On the basis of the results of epidemiological examinations described in four parts of the paper the qualitative and quantitative health needs of the stomatognathic system are discussed in the environment of learning and breeding (preschool, elementary school, secondary school, university), living (regional health clinic, health centre) and work (industrial plant clinic). In the assessment of the health needs in relation to quantitatively defined populations the possibilities of their realization are discussed. It is thought that the needs for therapeutic intervention are greatest in secondary school population, university students and patients in health centres and regional clinics. PMID- 2104344 TI - [Trials of remineralization of artificially produced enamel lesions]. AB - The purpose of the study was checking in vitro whether after application of calcifying preparations remineralization occurs of artificially damaged enamel prisms. The study was carried out on 32 enamel samples obtained from 8 human teeth. For remineralization saturated solutions were used of phosphate-calcium compounds in the form of fluid or gel. The degree of demineralization and remineralization of enamel was assessed on the basis of images of enamel breaks in JSM-50A scanning microscope. Partial remineralization of artificially damaged enamel was found. Detailed evaluation of the remineralization progress requires extension of investigation methods. PMID- 2104345 TI - [Congenital absence of permanent teeth]. AB - In 76 patients treated at the Department of Conservative Stomatology, Institute of Stomatology, Medical Academy in Lublin congenital absence of anlages of permanent teeth was found. The patients were aged 8 to 18 years, including 49 girls and 27 boys. In the whole group absence of 214 teeth was noted, i.e. 136 in girls and 78 in boys. In the examinations it was observed that congenital absence of permanent teeth was more frequent in girls than in boys, 2) most frequently only one tooth was absent in a given patient, 3) upper teeth were lacking more frequently than lower teeth, and absence of right teeth was more frequent than left teeth, 4) the greatest group among absent teeth were upper lateral incisors, while second upper molars in the maxilla were least frequently absent. PMID- 2104346 TI - [Determinations of magnesium, iron and copper in the saliva of healthy subjects]. AB - In 70 healthy subjects aged from 7 to 60 years centrifuged mixed, resting saliva obtained before breakfast was analysed for the presence of magnesium, iron and copper. The studied group was divided into three subgroups: I--7 to 14 years, II- 18 to 28 years, and III--from 48 to 60 years. Significant age-related differences were found in the magnesium content between group I and II and between I and III. No statistically significant differences were observed in the content of iron and copper, and in the values of the iron-copper index between the analysed subgroups depending on sex and on age. PMID- 2104347 TI - [The condition of the stomatognathic system in children with gluten-dependent coeliac disease]. AB - Stomatological examination was carried out of 38 children with coeliac disease. The condition of teeth with regard to caries was better than in children without coeliac disease. Occlusal abnormalities were noted in one-third of patients, in one-third of children with mixed teeth the dental age was delayed in relation to calendar age. No periodontal and mucosal changes were observed. The state of oral hygiene was estimated as good. PMID- 2104348 TI - [Atrophy of the mandible and maxilla as complication of treatment and healing of jaw fractures]. AB - The authors discuss in the light of literature data the causes of bone atrophy and report two own cases of extensive atrophy of the mandible and atrophy of the maxilla developed during treatment of their fractures. Parallel mandibular atrophy in a patient aged 67 years was observed 3 years after surgical union of fractured fragments of the edentulous mandible with metal plates. The cause of atrophy is related by the authors to prolonged malnutrition of the patient who had partial gaestrectomy 24 years earlier, and his failure to observe the suggested mandible immobilization during the required length of time. Considerable degree of maxilla atrophy in a 34-year-old man developed during treatment of a Le Fort III maxilla fracture. The atrophy affected mainly the apical base of the alveolar process, and it was observed 4 months after fracture. The cause was not systematic, prolonged without informing the stomatologist, and excessive traction was exerted by the rubber band in the chin-sling used for the treatment of the fracture. The treatment used in this case permitted to restore in the maxilla the proportions of bone structures approaching the normal ones. PMID- 2104349 TI - [Nebacetin in prevention of dry alveolus development after extraction and surgical removal of wisdom teeth]. AB - The authors carried out a clinical study of Nebacetin in the prevention of dry alveolus development after surgical removal of lower wisdom teeth. In a group of patients treated locally with Nebacetin tablets dry alveolus developed in 12% of cases, while in the control group this complication was noted in 27% of cases. PMID- 2104350 TI - [Surgical treatment of labial neoplasms and non-malignant epidermal hyperplasia in the material of the province hospital in Pila in the years 1979-1986]. AB - The author carried out a retrospective analysis of labial neoplasms and non malignant epidermal hyperplasia situated on the lips in patients treated surgically in the Province Hospital in Pila in the years 1979-1986. In that time period 32 patients with such changes were observed and 30 were treated. The lesions were situated on the lower lip in most cases. Most patients had neoplasms. The treatment was surgical, usually by the Bernard-Karapandzic method or the W-letter partial excision of the lip. Good results were obtained in 26 cases. In the light of the available literature and analysis of this small group the author concludes that surgical treatment of labial lesions, including neoplasms, using dermo-musculo-mucosal flaps from the nearest vicinity of the mouth provides the possibility of one-step filling of tissue defect and obtaining of good results both early and late. PMID- 2104351 TI - [Paramolar and distomolar teeth]. AB - The authors observed 8 patients with supernumerary molars (12 teeth in all). In accordance with Bolk's classification the authors found 5 paramolar teeth and 7 distomolar teeth (fourth molars). Four most typical cases are described. PMID- 2104352 TI - [Studies on the remineralization of enamel using radioisotopes]. AB - Enamel of human and bovine teeth was found to show sorption of free calcium ions after damage caused by short-term exposure to diluted hydrochloric acid or mechanical damage. The experiment was carried out using radioisotopes 32P and 45Ca and it was shown that majority of incorporated ions remained in the enamel after prolonged washing out with water as well as after brushing with toothpaste. A considerable stability of binding of the incorporated phosphate ions was noted in the damaged enamel after exposure to calcium salt solution, and marked stability of binding of the incorporated calcium ions after exposure to phosphate solution. PMID- 2104353 TI - [Micromorphology of dentine in rats with chronic exposure to ammonium fluoride]. AB - Wistar rats were exposed chronically to ammonium fluoride in a toxicological chamber where the concentration of fluoride ions was 0.0016 mg/m3 of air. The exposure lasted 6 hours daily five times weekly. The animals were sacrificed after 3.6 and 9 months of the experiment. Histological preparations were made from upper incisors with surrounding tissues. Microscopic examination demonstrated striation of dentine in the teeth, of these animals, which was due to development of decalcification bands. This type of changes was observed also by other authors and it is regarded as a characteristic feature of dentine damage by fluorine compounds. PMID- 2104354 TI - [Absence of permanent teeth buds in three generations of a family]. AB - Hypodontia is described in three generations of a family. Absence of the buds of permanent teeth was noted in 6 out of 12 family members. These cases confirm the hereditary aetiology of this anomaly. PMID- 2104355 TI - [Effect of fluoride prophylaxis on oral hygiene and condition of gingivae in school-children]. AB - The purpose of the study was assessment of exogenous organic and inorganic preparations of fluorides and their effects on the oral hygiene and condition of the gingivae in children living in an area with fluoridated drinking water and in another area without water fluoridation. The preparations were applied locally by brushing during 5 procedures at two-week intervals in the first and second years of the experiment. The oral hygiene was assessed by means of the plaque index and the condition of the gingivae by means of the gingival index. In the light of the obtained results it is regarded that these procedures had a favourable effect on the determined indices, and these effects were similar for both types of preparations. PMID- 2104356 TI - [A case of cuniculate epithelioma of the maxilla]. AB - A case of cuniculate epithelioma of the maxilla is presented. The patient was treated in the Outpatient Clinic and Department of Maxillofacial Surgery, Province Hospital in Pila. In accordance with the previously published descriptions of such lesions in the Polish and foreign literature the author found considerable difficulties in clinical and histological diagnosis, and described the characteristic features of the tumour. The results of histological examinations of two preparations were not unequivocal. The most characteristic feature of the tumour was its whitish colour, friability, spongy consistency and caseous masses expelled by pressure from numerous fistulae of the tumour. PMID- 2104357 TI - [Haemorrhagic cyst of the masseter--case report]. AB - Tumour-like changes in the masseter may be diagnosed as haemangiomas, lymphomas, lipomas, hernia of the muscle, benign hypertrophy or inflammatory or traumatic lesions. The authors describe a case of haemorrhagic cyst of rare location in the masseter and analysed the clinical features of this lesion. PMID- 2104358 TI - [In vitro assessment of metronidazole adapted to the treatment of periodontopathies]. AB - Chemical and biological assessment was done in vitro of a form of metronidazole for application into deep pouches in periodontal diseases. The obtained plates with metronidazole contained 1.4 mg (37%) of pure substance. Comparing the effect of metronidazole release in time against a control plate it was noted that the drug was released during 3 days in similar proportions from the chemical and biological samples. PMID- 2104359 TI - [Periodontological therapeutic needs of selected age groups in Poland]. AB - The needs for periodontological treatment were assessed on the basis of the most modern needs index CPITN in 3 age groups 7, 12 and 35-44 years. The obtained results indicated that in children aged 7 and 12 years the highest need for periodontological treatment was in the first category of need (TN 1). In the group of adults the highest proportion was again in the 1 and 2 categories of need. The proportion of subjects with healthy periodontium was highest in children aged 7 years (51.89%) and lowest in the age group 35-44 years (0.66%). PMID- 2104360 TI - [Periodontological therapeutic needs of children aged 7 years assessed in the province of Cracow]. AB - The values of the CPITN index and the need for periodontological treatment were determined in 180 children aged 7 years in the Province of Cracow. The results were obtained and compared in children from the City of Cracow, Wieliczka and villages in that region. A good condition of the periodontium was found in children living in Wieliczka, that is a region under particular protection. The worst state of the periodontium was found in Cracow. In all, 50.0% of children required instruction and improvement of oral hygiene. The mean sextant value of healthy periodontium per one child was 4.39. PMID- 2104361 TI - [Assessment of the periodontium condition and therapeutic needs by the CPITN index in children aged 12 years in the province of Cracow]. AB - The aim of the study was assessment of the condition of the periodontium and therapeutic needs in children aged 12 years in the City of Cracow, Wieliczka and villages in the Province of Cracow. The total number of the studied children was 180 including 90 girls and 90 boys, 30 girls and 30 boys in each group. The number of sextants with healthy periodontium was 738, the mean value per one child was 4.10, it was higher in girls--4.24 and lower in boys--3.95. The per cent of children with healthy periodontium was 24.44%, the per cent of children with bleeding on probing was 30.56%, and with tartar--45.00%. The highest values of this parameter were found in Wieliczka children, and the lowest ones in village children. The needs for treatment of the periodontium in children aged 12 years were as follows: 75.56% required improvement of oral hygiene, 45.00% required removal of tartar. The lowest needs were in Wieliczka children--60.00%, and the highest in village children--86.67%. PMID- 2104362 TI - [Analysis of correlations between the content of various elements in hard tissues of milk teeth with and without caries]. AB - Using the method of atomic absorption spectrometry the levels of calcium, magnesium, zinc, iron, strontium, nickel, manganese, copper were determined in the hard tissues of milk teeth with and without caries and the interrelations between these elements were analysed The obtained results were subjected to statistical analysis with an IMP 85 m computer. In the present study the analysis of the interrelations between elements was based on correlations and regression analyses. Many statistically significant interrelations were revealed between Mn and Fe, Mn and Zn, Mn and Cu, Mn and Ni, Fe and Zn, Fe and Cu, Fe and Ni, Zn and Cu, Zn and Ni. A decrease of the correlation coefficients was noted in carietic teeth. For the highly correlated elements equations of simple regression were calculated. A significant correlations was noted between caries and the levels of Mg, Zn, Fe, Sr, Ni, Mn, Cu in the hard tissues in milk teeth. The carietic milk teeth contained less Mg, Fe, Sr, Ni, Mn and Cu and much more Zn as compared to teeth without caries. PMID- 2104363 TI - [Two-stage method of enamel remineralization]. AB - Two toothpastes were compared in vitro for assessing the effectiveness of a two stage process of enamel remineralization after damage inflicted by means of acid. One paste contained added free anions essential for the remineralization process, the other paste contained analogous free cations. The remineralization process was based on sorption of free PO4(3-) or Ca2+ ions at the site of damaged enamel and development of calcium phosphate in situ. The study was carried out using phosphorus and calcium radioisotopes, electron microscope and X-ray microanalyzer. PMID- 2104364 TI - [A trial of assessment of the realization of the programme of stomatological health service for the Nowy Sacz Province in the years 1976-1986]. AB - The epidemiological situation was evaluated in the Nowy Sacz Province in school children and adolescents aged 7, 12 and 14 years in urban and village areas in the school-years 1975-76 to 1985-86. The DMF index, the DMF pattern and the percent proportions of children receiving fluoride prevention of caries were calculated. The number of dentists employed during the period of 10 years was compared. The data are presented in tables. It was found that the proportion of children receiving health care for caries prevention has increased, the mean DMF value in children aged 12 years fell from 4.9 to 4, and favourable changes occurred in the DMF pattern. PMID- 2104365 TI - [Solcoseryl--dental adhesive paste--in the treatment of postextraction alveolitis]. AB - After a study in three maxillofacial surgery teaching hospital departments the authors evaluated the usefulness of Solcoseryl dental adhesive paste as compared to Apernyl in the treatment of postextraction alveolitis. Solcoseryl paste was found to shorten the healing period by about 50% in comparison with Apernyl. PMID- 2104366 TI - [Selected cases of oral mucosa carcinomas]. AB - The clinical picture and methods of surgical treatment are described in three cases of oral carcinoma with different sites of origin (buccal mucosa, alveolar process mucosa of the maxilla, and mucosa of the mandibular alveolar process and oral floor). After a survey of the pertinent literature and in the light of the presented cases attention is called to the need for one-stage surgical reconstruction of the tissue defect and simultaneous or early prosthetic rehabilitation. PMID- 2104367 TI - [The use of a computer to measure linear and angular variables for an assessment of symmetry of the base of the skull]. AB - The use of a computer is described to make linear and angular measurements of the base of the skull. A group of 19 adult skulls from mediaeval Poland were chosen for this study. The cephalometric analysis defined 11 linear and 9 angular morphological variables. An assessment of method error due to point location by the cursor was made by duplicate determination, and an assessment of symmetry was carried out by comparing angular values derived from basion (ba) for right and left sides of the maxillary dental arch, zygomatic arch and cranial base. The results demonstrate that skull measurements could be recorded with a small method error of 0.2 mm for linear, and 0.2 degrees for angular recordings. Mean values for the 21 variables in the sample were recorded and statistically tested for point placement accuracy using measures of skewness and kurtosis to detect gross distribution errors. PMID- 2104368 TI - [The dynamics of parodontal disease incidence in young subjects in Cracow in 1969 1988]. AB - The reported study was carried out on 1241 subjects aged from 5 to 25 years with symptoms of parodontal diseases who came to an outpatient clinic in the years 1969-1988. Gingivitis prevailed among the diagnoses--825 cases, while deep parodontal changes were found in 416 cases. The incidence of all parodontal diseases was higher in females, with the exception of ulcerative gingivitis which was more frequent in males. The patients from the City of Cracow prevailed over those from the provinces of Southern Poland, and the incidence of various disease entities varied in various years. PMID- 2104369 TI - [Clinical trials of solcoseryl in the treatment of parodontium diseases]. AB - The effect of Solcoseryl on the clinical state of the parodontium was assessed in 26 patients aged from 18 to 57 years with the diagnosis of deep parodontopathies. Each patient received 30 ampoules of 2 ml of Solcoseryl for one course of the treatment. Submucous injections of the drug near the teeth 13, 23, 33 and 43 were done as follows: during the first 10 days one ampoule daily, then 10 injections every other day, and 10 injections at three-day intervals. The condition of the parodontium was assessed before and after the treatment by means of the PI, GI, GBI and teeth mobility indices, and measurements of the depth of gingival pouches -K, and volume of fluid in pouches SFFR according to Brill. The therapeutic method applied in these cases had a good effect on reduction of gingivitis, bleeding and volume of secreted pouch fluid but had only a small effect on teeth mobility and depth of gingival pouches. PMID- 2104370 TI - [Periodontitis juvenilis--a new view on the aetiology and treatment]. AB - The development of views on the terminology and aetiology, and a new approach to the treatment of juvenile parodontitis are described. The verification of these views has contributed to the explanation of the role of the bacterial factor (Actinomyces actinomycetecomitans) in the development of parodontal changes. This made possible outlining of an optimal therapeutic programmes. PMID- 2104371 TI - [Incidence of parodontal diseases in workers of the Chelm Cement Plant exposed to cement dust]. AB - The purpose of the study was evaluation of the incidence of parodontal diseases in workers exposed in their occupation to cement dust. Stomatological examinations were carried out in 127 workers of the plant (98 men and 29 women) aged 18 to 64 years. The control group comprised 117 persons (58 men and 59 women) aged 22 to 66 years. The condition of the parodontium was assessed and classified according to a 3-grade scoring system used for parodontal disease assessment. The obtained data were subjected to statistical and lysis. The intensity of the parodontal disease was greater in workers exposed to cement dust than in controls, and a very high incidence of deep parodontitis was noted in young workers in the plant. PMID- 2104372 TI - [Calcitonin in direct and indirect pulp capping]. AB - Calcitonin, the hormone produced by C cells of the thyroid playing a great role in calcium homeostasis, was used for direct and indirect pulp capping. This procedure was done on 200 teeth. Late follow-up after 12, 18 and 24 months or even longer was obtained in 146 cases: 110 with indirect pulp capping and 36 with direct capping. In the first follow-up examination 7 cases were regarded as failures, in late follow-up 5 failures were found, thus the total failure rate was 3.8%. The usefulness of calcitonin for biological treatment of pulp is unquestionable. PMID- 2104373 TI - [Ultrastructural pattern of enamel in initial caries]. AB - In beginning caries of particular interest are destructive changes in the enamel layers just below the surface. The studied material comprised about twenty enamel blocks obtained from 10 teeth with carietic spots removed for orthodontic reasons in children aged 12-14 years. The aim of the study was assessment of the initial enamel damage under electron microscope. In all electronograms of the enamel involved by the carietic spot various grades of demineralization of the enamel below its surface were seen. The changes in initial caries seemed well delineated from the remaining healthy enamel, although within the carietic focus demineralization was observed from very slight widening of the area around the prisms to massive destruction of prism structure. The changes in the carietic spot under electron microscope showed a wide variety of patterns of destruction of enamel prisms, although clinically the surface of the enamel involved by beginning caries was small and not damaged. PMID- 2104374 TI - [The condition of teeth in adult population aged 35-44 years living in a small town and in villages in the Province of Poznan]. AB - In an epidemiological study the condition of teeth was assessed in 120 subjects aged 35-44 years living in Sroda Wielkopolska and villages around it. Group I (60 subjects) lived in the town and group II (60 subjects) came from villages. Each group contained 30 women and 30 men. A high prevalence of caries was found, (99.16% for the whole studied population) with the mean DMF value 16.79%. The highest DMF values were found in group II in women--21.66. These high values of DMF were due to a great number of carietic teeth, teeth removed because of caries, and a relatively small number of teeth with fillings. Slight developmental disturbances of the enamel were observed. PMID- 2104375 TI - [Determination of abrasive properties of toothpastes by means of copper abrasion]. AB - The results are presented of the investigations of the proposed method for determination of the abrasive properties of toothpastes and raw materials used for their production. The method is based on brushing of copper surface with the studied paste in a device of own design, followed by chemical analysis of copper content in the mass after brushing. The optimal parameters of the work of the abrasive device were determined and the method for determination of copper content is described. For chemical analysis absorption spectroscopy in visible light and atomic absorption spectroscopy were used. The advantages of the proposed method of abrasive force determination was discussed comparing them to those of radioisotope assay. PMID- 2104376 TI - [Trials of using chitin and its derivatives in medicine and pharmacy]. PMID- 2104377 TI - [Mental nerve exeresis extended to involve the lower alveolar nerve]. AB - The author describes an original method of exeresis of the mental nerve bundle extended to involve the lower alveolar nerve. The experience is based on 500 cases of trigeminal neuralgia treated since 1949 by this method. PMID- 2104378 TI - [Abbe operation still currently used]. AB - Experiences in the treatment of 18 patients with cleft lip are described. The Abbe flap was utilized in the reconstruction of the upper lip. The operation, indications, some technical instructions and results are presented. PMID- 2104379 TI - [Assessment of surgical-orthopaedic management in craniofacial injuries complicated with nasal liquorrhoea]. AB - On the basis of experiences during 10 years with the cooperation of the departments of neurosurgery and maxillofacial surgery in the Province Hospital in Rzeszow the methods of surgical-orthopaedic management were assessed in craniofacial injuries. Out of 95 cases of craniofacial injuries treated in the years 1976-1985, in 42 cases (44.2%) nasal liquorrohea was present. For immobilization of the maxillary block in 32 cases Federspiel's traction was used, and in 5 cases interosseous binding of Adams. In 6 cases intermaxillary immobilization was applied. In this group of 42 cases of craniofacial injuries complicated with liquorrhoea in 24 (57.1%) liquorrhoea was stopped. PMID- 2104380 TI - [Backshifting of lower canines in occlusion regulation]. AB - In 17 patients the lower canines were shifted back during treatment of prognathic malocclusion and cross-bites. Stable devices with retraction loops, rubber or spring traction were used. The duration of active treatment was about 3 months, on average. During the treatment gaps after the removed premolars were closed completely, although this is nearly impossible when removable devices are applied. PMID- 2104381 TI - [The condition of oral mucosa and periodontium in drug addicts]. AB - The condition of the parodontium and oral hygiene were assessed in two 29-case groups of drug addicts before withdrawal treatment (hospital) and after it (in MONAR centre). The control group comprised 29 non-addicts. The PI index of Russel and OHI-S index were calculated. It was found that the mean value of PI and OHI-S was significantly greater before withdrawal treatment than after it, and in relation to controls. The values of both indices increased significantly with the duration of addiction. The authors concluded that drug-addiction through psychic deterioration leads to abandoning of oral hygiene which is the main cause of paradontal changes. PMID- 2104382 TI - [Relationship between grade I and II inflammatory foci and certain inflammatory ophthalmic diseases]. AB - The purpose of the study was demonstration of relations between grade I and II inflammatory foci in the oral cavity and certain inflammatory diseases of the eyes. Forty-three patients of either sex were studied. They were aged 19 to 78 years and were referred with the diagnosis of optic neuritis (intraocular and retrobulbar), iritis, retinitis and keratitis. Apart from routine clinical and radiological investigations the electrocutaneous test, the test for pulp viability with faradic current, and Schuller's iodine test were done. In 31 patients the electrocutaneous test was positive. PMID- 2104383 TI - [Treatment of teeth with simple or complicated pulp gangrene by a modified standard method]. AB - Using a modification of the standard method 102 teeth with simple or complicated pulp gangrene were treated. The modification of the standard method included insertion of inserts with 10% formalin solution into pulp chamber without introducing any drug into the root canals. The treatment comprised 3-6 visits. During the treatment in 26 cases complications developed after the first visit, and in 7 of them the treatment method was changed. Thirty-five teeth were examined again 1-3 years or more after the treatment. Good results of the treatment, with absence of clinical signs and with complete regeneration of bone structure was obtained in 34 cases. PMID- 2104384 TI - [Dental caries in children aged 7 and 12 years in the Province of Poznan]. AB - The authors present the results of stomatological epidemiological studies in the Province of Poznan in 1987 for establishing the prevalence of dental caries in children aged 7 and 12 years. The assessment was done using the index of caries prevalence, value of the mean DMF-H and dmf-h indices, and their components. In both studied age groups a high prevalence of caries was found, reaching 90% in children aged 7, years and 80% in those aged 12 years. The intensity of caries in children aged 7 years measured by the index DMF-h+dmf-h (mixed teeth) was high- 4.99. The intensity of caries was higher in children from rural areas (5.43) than in those from urban areas (4.455). The mean value of DMF-h was 0.49 for the whole population studied, and 0.41 for urban children and 0.56 for rural children. The mean DMF-z value in children aged 12 years was below 3.0 (2.34), and it was higher in children from rural areas (2.96) than in those from urban areas. The values of these indices were influenced mainly by high mean numbers of milk and permanent teeth with active caries. In the studied population a small number of filled teeth was noted. PMID- 2104385 TI - [24-hour fluctuations of the values of certain components of the saliva and dental plaque in school children]. AB - 24-hours changes were studied in the saliva and dental plaque of the concentrations of total fluorine, inorganic phosphate and protein, and of pH value. The study was carried out in two groups of school children: I--control, II -subjected to contact fluoridation. The obtained results showed that circadian changes occurred in controls and in children subjected to fluoridation. PMID- 2104387 TI - [Cortical bone hypertrophy in infants situated in the maxilla]. PMID- 2104386 TI - [Clinical evaluation of metronidazole in the treatment of the periodontal abscesses]. AB - On the basis of clinical examination it has been found that Metronidazole which was applied in 24 patients suffering from periodontal abscesses produced healing effects, lessened their pain and did not cause any side reactions. The values of PI (Russell rate) were considerably lower after the treatment comparing to the initial state, which confirms the therapeutic effectiveness of the drug. PMID- 2104388 TI - [Corrective osteotomy of facial skeleton in its post-traumatic deformity]. AB - Osteotomy with reposition of fractured fragments of the facial skeleton is the most effective method of treatment of post-traumatic deformities. In this way it is possible to correct permanently the position of the bones, to restore normal facial features and adequate conditions for the function of the stomatognathic system, respiration and articulation. A condition of success is good early planning of the operation with consideration of the vascularization of bones after osteotomy and effective reposition of bone fragments as well as a narrow slit of the incision for sparing of bone tissue. A condition of healing of the incision is good immobilization of bone fragments. PMID- 2104389 TI - [Maxillary sinus diseases--borderline of stomatological surgery and laryngology]. PMID- 2104390 TI - [Delaire's facial mask in the treatment of anterior prognathic anomalies]. AB - The authors present the technique of treatment of pseudo Class III malocclusion using an orthopedic Delaire's face mask. The use of the method is illustrated with 3 clinical cases. PMID- 2104391 TI - [Extraction of permanent teeth in orthodontic treatment]. AB - The basis for the analysis were case records of the patients treated in the Orthodontics Department of the Institute of Stomatology, Medical Academy in Warsaw, in the years 1980-1986, plaster models, radiological and photographic documentation. For a more detailed analysis of the material the extracted teeth, the orthodontic devices used in the treatment, the active elements used for displacing of teeth, and the duration and course of the treatment were considered. The analysis of the presented material shows that the treatment with extraction of permanent teeth as a basic procedure gave satisfactory results in cases of anomalies of teeth. In other cases it could be an adjuvant method used as a stage of the treatment and to reduce the time of treatment. PMID- 2104392 TI - [Assessment of the condition of the parodontium in children undergoing maxillary orthopaedic treatment with reference to malocclusion, groups of teeth and duration of treatment with orthodontic devices]. AB - The condition of the parodontium was studied in 281 children. Group I comprised children with malocclusion treated by maxillary orthopaedic methods, group II- children with non-treated malocclusion, group III--children with normal occlusion. The condition of the parodontium was assessed in various types of malocclusion, in groups of teeth and in relation to the duration of treatment with maxillary-orthopaedic devices. The parodontium was evaluated using the indices GI and PMA. The highest prevalence of parodontitis was found in cases of isolated crowding of teeth. Changes were observed, most frequently, at the lower incisors. With time of device use the values of the GI and PMA indices increased to a peak value in the 2nd year of the treatment, while past that time these values fell. PMID- 2104393 TI - The difficult challenge of cloning the angiotensin II receptor. AB - The vasopressor peptide angiotensin II exerts its cellular effects through a membrane-bound receptor coupled to a G protein. Biochemical and pharmacological analyses of this receptor already identify two different membrane-bound receptors and one cytosoluble angiotensin-II-binding protein. Nevertheless, the purification of the membrane-bound form(s) appears to be difficult. In the absence of purified protein, two cloning strategies of the gene have been explored: (1) expression cloning, identifying the functions of the protein expressed from a cDNA library in COS cells or Xenopus oocytes, has been unsuccessful until now; (2) analogical cloning, trying to identify related members of the seven transmembrane segment receptor family, which could be related to angiotensin receptors, identifies the mas oncogene and two related genes. However, there are accumulating data to exclude their involvement in angiotensin binding. PMID- 2104395 TI - Glucocorticoids in blood pressure regulation. AB - Glucocorticoid excess is associated with hypertension in man and in animals. This type of hypertension is of rapid onset and independent of salt intake; it can be inhibited by glucocorticoid antagonists, such as RU486. In normal rats, RU486 blunts vascular reactivity to norepinephrine and angiotensin II. In normal rats on low-salt diet, it induces a fall in blood pressure of approximately 20 mm Hg, due to decreased vascular resistance. This suggests that in some conditions, endogenous glucocorticoids contribute to the maintenance of blood pressure by enhancing vascular reactivity. PMID- 2104394 TI - Mode of action of angiotensin II and vasopressin on their target cells. AB - In this short review, the cellular mode of action of angiotensin II and arginine vasopressin is described with emphasis on the transmembrane signalling system. Two target cells are considered: the zona glomerulosa cell of the adrenal gland and the vascular smooth muscle cell. The information provided should help practitioners in endocrinology and hypertension to understand the physiological concepts which are expected to form the basis for future therapeutic developments. PMID- 2104396 TI - A unifying hypothesis of sodium and water regulation in health and disease. AB - Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. In recent years, the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in man, it has been found that the nonosmotic release of vasopressin is consistently associated with the activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and in the activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context, neither total extracellular-fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade, or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae, and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV). initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104397 TI - Immunoradiometric assay of active renin versus determination of plasma renin activity in the clinical investigation of hypertension, congestive heart failure, and liver cirrhosis. AB - We compared the determination of plasma renin activity (PRA) and the direct immunoradiometric measurement of active renin (AR) as ways of assessing the activity of the renin-angiotensin system in normal volunteers and in patients with hypertension, heart failure, or liver failure. The levels of plasma renin substrate, angiotensinogen, and the ratio of PRA to AR concentration did not differ in the normal volunteers and the patients with essential or renovascular hypertension. However, compared to the volunteers, patients with severe heart or liver failure had markedly reduced plasma renin substrate levels, which led to a considerable underestimation of AR concentration when it was measured by PRA. PMID- 2104398 TI - Catecholamines and blood pressure regulation. AB - Catecholamines (CAs) play a central role in the regulation of blood pressure. Sympathetic adrenal effects are ultimately elicited by the neurotransmitter norepinephrine and the hormone epinephrine. Their release is under the control of higher centers and is finely modulated by several factors such as presynaptic receptors. Recent evidences suggest that also the peripheral dopaminergic system can participate in blood pressure regulation intervening in the blood flow regulation of some regions, and in sodium-water balance. The measurement of CAs in biological fluids has greatly enhanced our knowledge on the mechanisms regulating blood pressure and is widely applied in cardiovascular research. Clinical applications of CA measurement are still limited to the diagnosis of pheochromocytoma and to the differential diagnosis of hypotensive syndromes. PMID- 2104399 TI - Characterization of the angiotensin II receptor. AB - We present a brief overview of the present knowledge on the structural and molecular properties of angiotensin II receptors and the various attempts to determine their primary structures, with special reference to our strategy for receptor purification. The strategy involves covalent labeling of the receptor with synthetic biotinylated photoactivatable probes, followed by indirect affinity chromatography on immobilized streptavidin. The various applications of these probes to the study of structural and molecular properties and to the cell biology of angiotensin II receptors are discussed. PMID- 2104400 TI - Hormonal control of arterial pressure and water electrolyte metabolism. 33rd International Henri-Pierre Klotz Days of Clinical Endocrinology. Paris, May 1990. PMID- 2104401 TI - [Progression to ischemic heart disease in subjects with coronary calcification as evaluated by computed tomography]. AB - It is well known that coronary artery calcification develops in patients with advanced coronary sclerosis. Currently, it can be easily detected by computed tomography (CT). We studied the correlation of CT-detected coronary calcification with its progression to myocardial infarction, and further with the prognosis in various patients who did not have symptoms suggesting ischemic heart disease. The subjects consisted of 241 patients (136 males, 105 females) with a mean age of 61 years, categorized as a calcified coronary artery group (82 patients) and a non calcified coronary artery group (159 patients). In all the subjects nonenhanced serial cardiac-CT scans were performed with a GECT/T 9800 for detecting coronary calcification. The mean follow-up period was four years in both groups. Among the 82 patients with coronary calcification, four developed myocardial infarction (4.9%) and 14 patients died (17%). Among the 159 patients without coronary calcification, none progressed to myocardial infarction, but 17 patients died unrelatedly (11%). Although there was no significant difference in mortality between the two groups, there was a statistical significance (p less than 0.005) as to the incidence of progression to myocardial infarction. In males, there was no significant difference (13 vs 12%) in mortality between the two groups, but the calcified group had a higher incidence of progression to myocardial infarction than that of the non-calcified group (5.5 vs 0%). In females, the calcified group had higher mortality (26 vs 8.9%) and a more frequent incidence of myocardial infarction (3.7 vs 0%) than did the non-calcified group. In conclusion, patients with coronary artery calcification are likely to develop coronary artery disease rather rapidly, even though asymptomatic. Therefore, detection of coronary calcification by non-enhanced CT is helpful for estimating the prognosis of coronary artery disease. PMID- 2104402 TI - [Usefulness of rest-redistribution on thallium myocardial scintigraphy in patients with acute myocardial infarction by SPECT: analysis by bull's eye and unfolded map images]. AB - The purpose of this study was to clarify the clinical significance of rest redistribution in myocardial scintigraphy (SPECT) in acute myocardial infarction (AMI). Thirty patients with AMI within one week after the onset of attack were studied. SPECT images were obtained 10 min and three hours after injection of 201Tl. Bull's eye images and unfolded map images were prepared. A 201Tl uptake was studied at the infarct and non-infarct sites. Exercise SPECT and radionuclide angiography (RNA) were performed in all patients one month after the onset of AMI, and the findings were compared with clinical and coronary angiographic (CAG) findings. 1. Redistribution of thallium at rest was observed at the infarct sites in nine of the 30 patients. 2. Redistribution at rest was observed at the non infarct sites in eight patients. 3. Redistribution at rest was observed during exercise SPECT one month after the onset of AMI in patients with redistribution at rest in the acute phase. 4. In patients with redistribution at rest at the infarct site, left ventricular ejection fraction (EF) improved one month after the onset of AMI (delta EF greater than 5%), but it decreased slightly during exercise. 5. Wall motion at the infarct site was not much impaired in patients who showed redistribution at rest at the infarct site. 6. Angina pectoris and recurrence of myocardial infarction were observed more frequently in those with redistribution at rest on SPECT. 7. No characteristic findings were obtained on CAG in those with redistribution at rest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104403 TI - [Coronary circulation, myocardial metabolism and cardiac catecholamine flux in patients with syndrome X]. AB - To clarify the pathogenesis of syndrome X (Sx), hemodynamics, coronary circulation, myocardial lactate metabolism and cardiac catecholamine flux were studied before and during bicycle ergometry in 25 patients (pts) and these data were compared with those in 15 with effort angina (EA) and in eight controls. The results were as follows: 1. The cardiac index during exercise decreased in EA pts probably due to their coronary lesions, while those in the controls and Sx were well preserved. 2. An increase of coronary blood flow during exercise, both in Sx and EA pts, was significantly impaired and the myocardial extraction ratio of lactic acid was significantly lower compared with those in the controls. The cardiac norepinephrine release during exercise was markedly higher in Sx, compared with that in controls and in EA. These results suggested that in Sx, excessive sympathoadrenergic stimulation may play an important role in restricting coronary reserve and in accelerating myocardial anaerobic metabolism. PMID- 2104404 TI - [Painless myocardial ischemia in diabetic patients with coronary artery disease: evaluations by treadmill exercise tests]. AB - To elucidate the prevalence and features of painless myocardial ischemia among diabetic patients, 44 consecutive patients with angiographically-documented coronary artery disease and positive treadmill tests were examined. They were 26 with diabetes and 18 without it. Painless myocardial ischemia was defined as the absence of chest pain with 1 mm or more ST segment depression during the exercise stress tests. The severity of ischemia was determined by the magnitude of the ST segment depression. Painless myocardial ischemia was observed in 18 of the 26 (69%) diabetics, and in three of the 18 (17%) non-diabetics (p less than 0.005). The frequency of painless ischemia in the diabetics was relatively high regardless of the severity of ischemia, while painless ischemia was less frequent in the non-diabetics with severe ischemia. With a level of 2.5 mm ST depression, 11 of 12 (92%) diabetics were free of pain compared to four of 11 (36%) non diabetics (p less than 0.01). Absence of chest pain during the exercise tests was not concordant with prior angina in diabetics, as opposed to non-diabetics in whom both clinical and exercise-induced angina developed concordantly. The diabetic patients without chest pain had a higher prevalence of three major diabetic complications such as neuropathy, nephropathy and retinopathy compared to those developing chest pain (p less than 0.025). It was concluded that in diabetics, painless myocardial ischemia is frequently observed during exercise stress tests and its prevalence is relatively high regardless of the severity of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104405 TI - [Early diastolic dysfunction of the left ventricle and its relation to histopathological findings in patients with diabetes mellitus]. AB - The relation of left ventricular diastolic function and the histopathological findings of the myocardium in patients with diabetes mellitus were observed using echocardiography and endomyocardial biopsy. The subjects consisted of six diabetic patients (mean age 49.3 years) and eight normal control subjects (mean age 44.8 years). Coronary angiography had no significant stenotic lesions in their coronary arteries. Their diabetic complications were mild to moderate in severity. Echoes from the left ventricular margin of the septum and from the posterior left ventricular wall were traced on a digitizing board; then the isovolumic relaxation period, rapid filling period, slow filling period and atrial contraction period were determined to calculate fractional shortening (FS), isovolumic relaxation time (IRT), and three filling volumes (RFV, SFV and ACV). The quotients of the left ventricular filling volume and stroke volume were also determined. Right ventricular endomyocardial biopsies were performed to determine the diameters of myocytes, the percentage of fibrosis and the eccentricity e, as a parameter of the degree of myocardial dysarrangement. The results were as follows: IRT was significantly longer and RFV/SV was significantly greater in patients with diabetes mellitus than those among the controls. Also the diameters of myocytes and the percentage of fibrosis were significantly greater, while the eccentricity e was less compared to that of the controls. There were no significant correlations, among IRT, RFV/SV, the diameters of myocytes, and eccentricity e, but the percentage of fibrosis significantly correlated with IRT and RFV/SV (r = 0.62, r = -0.63). IRT and RFV/SV were mainly responsible for the percentage of fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104406 TI - Clinical characteristics of cardiomyopathy with mild dilatation. AB - The clinical features of 20 patients with mildly dilated cardiomyopathy (MDCM) were investigated by electrocardiography and echocardiography. MDCM was defined as conditions with: 1) left ventricular end-diastolic dimension between 55 and 65 mm and 2) left ventricular fractional shortening between 10 and 25%. Nine patients (45%) had no histories of congestive heart failure. Eight patients had atrial fibrillation, and the other 12 patients were in regular sinus rhythm. Two patients had supraventricular premature contractions and five patients had ventricular premature contractions. One patient had paroxysmal atrial tachycardia. During the 40-months' span of this echocardiographic study, left ventricular end-diastolic dimension (60.8 +/- 3.8 mm to 57.3 +/- 4.6 mm) and left ventricular fractional shortening (17.2 +/- 4.6% to 22.7 +/- 7.1%) did not change significantly. One patient died suddenly. These results suggest that 1) some patients with MDCM have neither definite histories nor symptoms to suggest heart failure; 2) the hemodynamic conditions of patients with MDCM do not always deteriorate, but rather stabilize, and even improve during follow-up periods; 3) several types of arrhythmias can be observed, even in standard resting electrocardiograms; and 4) patients with MDCM may die suddenly. PMID- 2104407 TI - [Doppler echocardiographic features of the atrial and ventricular filling modes and their significance in restrictive myocardial diseases]. AB - The filling modes into the right atrium and both ventricles were observed using pulsed Doppler echocardiography in six cases of restrictive myocardial diseases, and these were compared with those of 13 cases of constrictive pericarditis, six cases of lone atrial fibrillation and 16 healthy subjects. Special attention was paid to the mechanical properties of the cardiac walls which might be reflected in the filling modes. 1. In the restrictive cases, right atrial filling from the superior caval vein during ventricular systole was reduced in velocity and duration, but the atrial filling during ventricular diastole was not appreciably changed. This flow pattern was similar to that of lone atrial fibrillation, indicating reduced distensibility or impaired contraction and ejection fraction of the right atrium. In constrictive pericarditis, the right atrial filling time was shortened both in ventricular systole and diastole, reflecting stiffening of the pericardium. 2. In the restrictive cases, the first half of the left ventricular rapid filling wave was steep and the skirt of the descending limb was prolonged, while there was no such tendency in the right ventricle. In constrictive pericarditis, the rapid filling time was shortened in the right ventricle, and was not significantly changed in the left ventricle. 3. The differences in the atrial and ventricular filling patterns between restrictive myocardial disease and constrictive pericarditis may serve to distinguish these two disease entities. PMID- 2104408 TI - [Studies of hyperkinetic circulatory state in chronic anemia]. AB - To clarify the hemodynamics of anemia, 28 patients with iron deficiency anemia were investigated in respect to their parameters of left ventricular (LV) systolic and diastolic function. The subjects were categorized in three groups: 1) patients (pts) with severe anemia, whose hemoglobin (Hb) concentration was less than 7 g/dl (N = 7); 2) pts with moderate anemia, whose Hb concentration was between 7 and 10 g/dl (N = 13): and 3) pts with mild anemia whose Hb concentration was between 10 and 12 g/dl (N = 8). Changes in hemodynamic parameters were observed before and after treatment in 14 subjects. These results were compared with those of normal subjects (N = 11). In the anemic patients, LV stroke volume (SV), and heart rate both increased. An increase in SV was accompanied by an increase in LV preload (LV diastolic diameter = LVDd by M-mode echocardiography) and an increase in the Doppler parameters of early diastolic filling (peak velocity in the rapid filling phase, acceleration rate, and deceleration rate). SV correlated roughly with LVDd (r = 0.44, p less than 0.05). In addition, the indices of LV contractility as measured by the pulsed Doppler method (ET/PEP) and by M-mode echocardiography (mVcf) also increased. These factors which contributed to hyperkinetic circulation were restored as the anemia improved. It was concluded that an increase in SV is an important determinant of high cardiac output in chronic anemia, because it parallels the severity of anemia. The change in SV is preload-dependent, and is suspected of being LV contractility-dependent. PMID- 2104409 TI - [Evaluation of physiological mitral regurgitant flow using transesophageal Doppler echocardiography]. AB - Transesophageal Doppler echocardiography (TEDE) was performed to determine the incidence of physiological mitral regurgitation (MR) and the characteristics of regurgitant blood flow in presumably normal subjects. TEDE included color flow mapping, pulsed Doppler echocardiography and M-mode color flow mapping. Sixty-six surgical patients who had no histories or physical evidence of cardiac abnormalities were studied using TEDE under general anesthesia. MR flow was detected in 94% (62/66) of the patients by transesophageal color flow mapping. Transesophageal color flow mapping clearly differentiated physiological MR flow and signals generated from mitral valve closure. In 40% (25/62) of the patients whose MR flow was detected, transesophageal pulsed Doppler echocardiography (TEPD) revealed regurgitant signals lasting less than half of systole. Only 31% (19/62) had peak MR flow velocities greater than 1 m/sec. TEPD could not detect high velocities reflecting the pressure gradients across the mitral valve. Since the regurgitant volume was very small, TEPD may have been incapable of detecting high velocity components of the MR flow. In conclusion, our data suggested that nearly all normal subjects may have mild mitral regurgitation. PMID- 2104410 TI - [Intraoperative epicardial two-dimensional and pulsed Doppler echocardiography for assessing functional tricuspid regurgitation]. AB - Intraoperative epicardial two-dimensional and pulsed Doppler echocardiography (PDE) were performed for 44 patients undergoing open mitral valve surgery to determine the presence and severity of functional tricuspid regurgitation (TR). The findings of intraoperative epicardial PDE performed before cannulation for extracorporeal circulation were compared with those of preoperative transthoracic PDE test. The findings of intraoperative PDE after cessation of the extracorporeal circulation were compared with postoperative transthoracic PDE and clinical findings. Pansystolic pulsed Doppler signals recorded in the right atrium were defined as TR. The grade of TR was assessed transthoracically and intraoperatively on the basis of its maximum distance from the tricuspid valve orifice. To perform intraoperative echocardiography, the transducer was sterilized with ethylene oxide gas and placed directly on the right atrium. The pulsed Doppler signals were recorded from nine sample volumes set in the right atrium, and the TR was graded. There were no complications using this technique. Intraoperative PDE prior to the extracorporeal circulation was more sensitive and specific for detecting TR (100% and 80%, respectively) than was preoperative transthoracic PDE (92.8% and 46.7%, respectively). All patients without TR by intraoperative PDE before cannulation for extracorporeal circulation had the competent tricuspid valves. The patients who were diagnosed as having no TR by intraoperative PDE after cessation of the extracorporeal circulation had no significant TR during the follow-up period. It was concluded that intraoperative PDE is a practical method which allows surgeons to assess the presence and severity of TR intraoperatively and to evaluate tricuspid valve function after intracardiac procedures. PMID- 2104411 TI - [Left ventricular asynergy and myocardial necrosis accompanied by subarachnoid hemorrhage: contribution of neurogenic pulmonary edema]. AB - One hundred-thirty patients with acute subarachnoid hemorrhages were investigated to examine the relationship of neurogenic pulmonary edema to cardiac lesions. Abnormal electrocardiograms were observed in 99 of these patients. Left ventricular asynergy was detected in nine of the 99 patients by two-dimensional (2D) echocardiography. In addition to 2D echocardiography, chest radiography, electrocardiography, serum CPK measurements and cardiac catheterization were performed for these nine patients in the acute stages of their subarachnoid hemorrhages. Abnormal electrocardiographic findings included prolongation of QT intervals and marked ST-T changes, which were observed in all nine patients. Pulmonary edema associated with increased pulmonary arterial wedge pressures were noted in seven, and increases in CPK and MB-CPK in all patients, suggesting the occurrence of myocardial necrosis. An increase in serum catecholamine was observed in all patients. Coronary angiography was performed in two patients and revealed normal coronary arteries in both. Biopsy findings were available in three and demonstrated severe fragmentation at the sites of left ventricular asynergy. Pulmonary edema, electrocardiographic abnormalities and left ventricular asynergy improved markedly during the courses of hospitalization. We concluded that left ventricular asynergy and myocardial necrosis may occur during the acute stage of subarachnoid hemorrhage and could produce neurogenic pulmonary edema rather than or in addition to permeability edema. PMID- 2104412 TI - [Medical and surgical treatment for patients with dissecting aneurysms of the aorta]. AB - The medical and surgical treatment of 96 patients of dissecting aneurysms was reviewed. There were 42 patients with Stanford type A dissecting aneurysms, 19 of whom received medical treatment and 23 of whom had surgical treatment. Among 54 patients with Stanford type B dissecting aneurysms, 24 had medical and 30 had surgical treatments. The treatment results and the long-term outcomes were studied using the Kaplan-Meier method, categorizing the subjects in non-survivor (in-hospital) and survivor groups. The results indicated that those with surgical treatment had a higher survival rate (75%) in the early post-operative course, for both type A and type B aneurysms. However, the long-term outcome of the survivor group was not different between type A and type B aneurysms regardless of type of treatment. Fifty-six percent of cases with type A aneurysms with serious complications survived by medical treatment alone, and no intimal tears were visualized on angiogram. Therefore, it was suggested that, in patients who had no angiographically defined intimal tears in the acute phase, medical treatment may be more effective, even for type A dissecting aneurysms. PMID- 2104413 TI - [Echocardiography in patients with malignant metastatic neoplasms of the heart and great vessels]. AB - Two-dimensional echocardiography was used to study malignant metastatic neoplasms of the heart and great vessels in 20 patients, 13 males and seven females, whose ages ranged from 15 to 72 years. Five patients had lung cancer; two each had breast cancer, malignant melanoma, hepatoma and one each had gastric cancer, urinary bladder cancer, adrenocortical carcinoma, malignant lymphoma, angiosarcoma, fibrosarcoma, leiomyosarcoma; and two had cancers with unknown primaries. Tumor invasion was demonstrated echocardiographically in the left atrium in one each with breast cancer, fibrosarcoma and gastric cancer; in the right atrium in two with hepatomas; in the right atrium and right ventricle in one patient with adrenocortical carcinoma; in the left ventricle in one with lung cancer; and in the pulmonary artery in one with malignant melanoma. Massive pericardial effusion was observed in 11 of 20 patients; two with pericardial tumors including malignant lymphoma and lung cancer. We conjectured that metastatic tumors in the right cardiac cavities came through the inferior vena cava, and other tumors in the left atrium, left ventricle and pericardium developed from direct extension of the primary lesions. There was an 80% mortality of the patients during the observation period, and the average survival period after the diagnosis of cardiac metastases was 5.5 months. However, one patient was still living after two years of radiation therapy and chemotherapy. Echocardiography proved a useful, non-invasive means for the detection and follow up observation of metastatic cardiac tumors. PMID- 2104414 TI - [The relationship of osteoporosis to mitral annular and aortic valvular calcification in elderly women]. AB - Mitral annular calcification (MAC) and aortic valve calcification (AVC) are thought to be attributable to the aging process, and their incidences are especially high in elderly women. It is known that the incidence of osteoporosis (OP) is also relatively high in elderly women. Therefore, we investigated the relationship of OP to MAC and AVC. The study subjects were 39 women aged 70-89 years. MAC and AVC were investigated by echocardiography. The amount of bone mineral (BM) in the lumbar vertebral bone was measured by computed tomography using a bone phantom and the standard amount of CaCO3. MAC and AVC were detected in 14 (35.9%) and 19 (48.7%) of the 39 subjects, respectively, and there was a tendency of coexistence of MAC and AVC. There was no significant age difference between patients with and without MAC. The amount of BM was significantly lower in patients with MAC than in patients without it (27.1 +/- 8.2 vs 53.5 +/- 27.3 mg/cm3: p less than 0.01). There was no correlation between the amounts of BM and AVC. In conclusion, the amount of BM is clearly lower in elderly women with MAC, suggesting that MAC may be related to OP etiologically. However, there was no clear relationship between AVC and OP. Thus, the etiologies of AVC and MAC may be different. PMID- 2104415 TI - [A new noninvasive method for calculating pulmonary to systemic flow ratio (Qp/Qs) in patients with atrial septal defect using multigated Doppler echocardiography]. AB - The number of patients with atrial septal defect (ASD) who undergo intracardiac repair without cardiac catheterization has been increasing. A noninvasive quantitative method to estimate the Qp/Qs ratio in this disease is therefore needed, but no simple, accurate method has yet been reported. The purpose of this study was to devise a new clinically useful method. Study materials consisted of 15 patients with ASD who were catheterized and five post-operative patients. For this study a multigated Doppler echocardiographic instrument (Fujitsu ME 120A) was used, which allowed us to ascertain Doppler shift frequency at 64 consecutive sampling volumes up to 13 cm in depth simultaneously. In the parasternal four chamber view, the cursor was set so as to cross obliquely the right ventricular inflow tract just below the tricuspid valve and the left atrium, just above the mitral valve. Two blood flow profiles were obtained from the flow crossing the tricuspid and mitral valves. The multigated Doppler echocardiogram was recorded on videotape and then analyzed. (1) The encircling area between the profile and the base line was measured for tricuspid and mitral flow independently throughout diastole. After summing up each area of tricuspid (TA) and mitral (MA) flow profiles, the ratio TA/MA was obtained (area calculation method). (2) The flow volume passing through each tricuspid (TF) and mitral valve (MF) was calculated from the flow profile using the "ring approach" reported by Jenni, and the ratio TF/MF was obtained (flow calculation method).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104416 TI - [Incidence of atrial septal aneurysm: echocardiographic and pathologic analysis]. AB - We prospectively studied the echocardiographic findings of an atrial septal aneurysm (ASA) to estimate its incidence and to clarify its clinical characteristics and significance. Post-mortem examination was also performed in three patients. Echocardiographically, ASA was defined as a bulging segment of the atrial septum localized in the fossa ovalis, either fixed in one direction or oscillating between the atria. It was classified in three types according to Hanley et al., i.e., Type 1A, protruding into the right atrium without oscillation; Type 1B protruding into the right atrium with oscillation, and Type 2, protruding into the left atrium with oscillation. Among 2,074 consecutive subjects in the echocardiographic study population, ASA was diagnosed in 26 patients (1.2%). This figure was slightly higher than those previously reported (0.6% to 1.0%). The extent of protrusion of the aneurysm was 8 mm or more in all patients, regardless of its direction, and it was assumed that this is a reasonable echocardiographic diagnostic criterion in the apical four-chamber view. All patients were over 51 years in age, with a mean of 71 years. Most patients (96%) had oscillation of their aneurysms. Twenty-one patients (81%) were of Type 2; one was Type 1A, and four were Type 1B. Post-mortem examination of three patients revealed septal protrusion toward the right atrium in all, and patent foramina ovale in two of them. Among the 26 patients, two (8%) had systemic embolic complications; one, cerebellar infarction, the other, cerebral infarction and mesenteric artery embolism. In conclusion, atrial septal aneurysm was observed in 1.2% of subjects undergoing routine echocardiography, with a distinctive distribution among patients over 51 years of age. Characteristically, it protrudes into the left atrium 8 mm or more, and it is sometimes associated with patent foramen ovale. Systemic embolism is a possible complication of this anomaly. PMID- 2104417 TI - [Ventriculo-arterial coupling during aerobic and anaerobic exercise in normal subjects]. AB - Physiological differences in aerobic and anaerobic exercise were assessed within the coupling framework between the left ventricle and the arterial system. In 10 normal men, the anaerobic threshold was estimated using sequential breath gas analysis during incremental ergometer tests. Direct arterial pressure and left ventricular echocardiograms were simultaneously recorded as its pressure was changed by phenylephrine or nitroprusside, and the slope (Ees) and volume axis intercept (Vo) of the end-systolic pressure (ESP)-volume relationship were determined. The effective arterial elastance (Ea) was expressed by the slope of the ESP-stroke volume relationship. Assuming that the Vo was unchanged from the resting state, the Ees and Ea were determined during exercise at aerobic and anaerobic work levels for each subject. During aerobic exercise, an increase in left ventricular end-diastolic volume and the tendency to decrease in ESP caused a significant fall in Ea by 30%. There was no significant change in Ees. Consequently, Ea/Ees which correlates inversely with left ventricular pump efficiency, decreased by 35%. During anaerobic exercise, Ea remained the same as during aerobic exercise, but Ees rose substantially by 89%. This caused a further reduction in Ea/Ees (-54%). Thus, ventriculo-arterial coupling during exercise is characterized by a decrease in Ea/Ees, indicating an augmentation of pump efficiency. This is primarily mediated by changes in loading conditions (decrease in Ea) during aerobic exercise, and by enhanced contractility (increase in Ees) during anaerobic exercise. PMID- 2104418 TI - [Evaluation of left ventricular mechanical energy efficiency and ventriculo arterial coupling in humans using the conductance catheter technique]. AB - To evaluate left ventricular mechanical energy efficiency and ventriculo-arterial coupling in humans, left ventricular pressure-volume relations were determined using the conductance catheter technique in 20 patients undergoing cardiac catheterization. The results were as follows: 1. A convex, curvilinear relationship was observed between end-systolic pressure-volume relations (Emax) and left ventricular ejection fraction (EF), as shown in the equation of EF = 28.5 x log (Emax) + 39.6 (r = 0.67, p less than 0.01, n = 20); EF remained nearly constant in the range of Emax greater than or equal to 4 mmHg/ml/m2, whereas, EF decreased markedly under the Emax of 4 mmHg/ml/m2. 2. A convex, curvilinear relationship was observed between Emax and mechanical energy efficiency (EW/PVA), as shown in the equation of EW/PVA = 30.5 x log (Emax) + 54.8 (r = 0.83, p less than 0.01, n = 16). 3. A concave, curvilinear relationship was observed between Emax and ventriculo-arterial coupling (Ea/Emax), as shown in the equation of Ea/Emax = -0.8 x (Emax)0.5 + 2.6 (r = -0.85, p less than 0.01, n = 16). Accordingly, EW/PVA was markedly decreased with changes in Emax in the range less than 4 mmHg/ml/m2, although it remained slightly increased above 4 mmHg/ml/m2. Ea/Emax was maintained constant (p less than 0.5) in the range of Emax above 4 mmHg/ml/m2 but was abruptly decreased when Emax was reduced below 4 mmHg/ml/m2. These results indicate that depressed left ventricle attempts to work effectively at the risk of mechanical energy efficiency and with suitable matching by aortic property. Application of pressure-volume relationships provides a new framework for evaluation and treatment of the failing heart. PMID- 2104419 TI - [Intracardiac flow vector measurement by simultaneous dual-frequency two-beam pulsed Doppler echocardiography]. AB - Conventional single-beam pulsed Doppler echocardiography has certain limitations in quantitatively measuring the intracardiac blood flow, because the Doppler incident-angle to the flow stream is uncertain. In the present study, the absolute velocity and direction of the intracardiac blood flow, i.e., flow vector, were measured using our newly-developed dual-frequency two-beam pulsed Doppler echocardiography. This instrument has two transducers with center frequencies of 3.5 MHz (main-beam) and 2.2 MHz (sub-beam) which are linked by two arms. Three potentiometers are set up by the three joints to sense the relative angles. Two velocity components at the intersection of the main- and sub-Doppler beams were measured simultaneously with different directional approaches. The flow vector was calculated manually from the two velocity components. The study population consisted of 18 healthy subjects ranging in age from 23 to 39 years. The left ventricular (LV) inflow vector was measured at the center of the mitral annulus, and the ejection flow vector was measured at the levels of the tip (E1) and the mid-portion (E2) of the anterior mitral leaflet in the LV outflow tract. The results were as follows: 1. The LV rapid inflow (R) was directed slight posteriorly towards the cardiac apex, and its average maximal velocity was 78 +/- 15 cm/sec (mean +/- SD). The LV inflow due to the atrial contraction was directed even more posteriorly than was the R, and its average maximum velocity was 43 +/- 10 cm/sec. 2. The LV ejection flows at E1 and E2 were directed slightly posteriorly rather than parallel to the interventricular septum, and the maximum velocity at E1 and E2 was 53 +/- 20 m/sec and 85 +/- 23 cm/sec, respectively. In conclusion, the dual-frequency two-beam pulsed Doppler technique allows quantitative measurement of the intracardiac blood flow dynamics regardless of the Doppler incident-angle to the flow stream. PMID- 2104420 TI - [Noninvasive evaluation of left ventricular function using new systolic time intervals obtained from continuous-wave Doppler echocardiography]. AB - Left ventricular function was evaluated using parameters derived from the flow velocity waveforms at the ascending aorta as obtained at the suprasternal notch by continuous-wave Doppler echocardiography in 39 patients; 12 with chest pain but without coronary stenosis, eight with angina pectoris; and 19 with myocardial infarction. Peak flow velocity and the time interval from the beginning of the Q wave of lead II of the ECG to peak flow velocity (Q-V peak) correlated with specific invasive hemodynamic parameters, such as max dp/dt and (max dp/dt)/IP (IP: total left ventricular pressure at the same instant) during isometric contraction of the left ventricle measured with a catheter tip manometer, and left ventricular ejection fraction (LVEF) obtained by bi-plane cineangiography (using the area-length method). There was no correlation between the peak flow velocity and the invasive hemodynamic parameters. However, significant negative correlations were observed between the Q-V peak time and max dp/dt, with r = 0.40 (p less than 0.05), and between the Q-V peak time and (max dp/dt)/IP with r = 0.61 (p less than 0.01). A negative correlation was obtained between the Q-V peak time and LVEF (r = -0.75, p less than 0.01). The regression equation was LVEF = 0.67 x (Q-V peak) + 176. To compare the effectiveness for predicting LVEF between the Q-V peak and the established systolic time intervals as PEP and PEP/ET, these time intervals were measured from flow velocity waveforms invasively obtained with a catheter-type electromagnetic flowmeter inserted into the ascending aorta in 14 patients selected from the original subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104421 TI - [Problems in patients with use of a ventricular assist device]. AB - The purpose of the present study was to review the results obtained in patients with a ventricular assist devices (VAD) in our hospital, and to discuss various problems concerning a VAD use, such as indications, right ventricular failure, and evaluation of cardiac function. Fourteen VADs were applied to 11 patients for left ventricular assist, including two for right ventricular assist and for one as biventricular assist with a VAD in the left and a biopump in the right. The clinical diagnoses of the patients were as follows: 10 ischemic heart disease, two valvular disease, one acute aortic dissection, and one corrected transposition of the great arteries. VADs were indicated in 11 patients because of difficulty in weaning from cardiopulmonary bypass (CPB), and in three patients because of cardiogenic shock after discontinuing CPB. Among the 14 patients, 11 had an effective VAD, six were successfully weaned from a VAD, and two survived. The VAD was ineffective due to uncontrollable bleeding and improper indications for the device, as in applying a one-sided heart assist when a biventricular assist was necessary. In spite of an effective VAD, five patients could not be weaned from VAD because of brain damage, sepsis, and hypoxia. After removing a VAD, four patients died; one due to mediastinitis, two due to respiratory failure, and one due to low output syndrome. All the four patients had renal failure followed by multi-organ failure finally, because of prolonged CPB time. The CPB time was shorter among the long survivors than in others. Cardiac function during assist and the weaning probability from a VAD were evaluated not only by the so-called on-off test, but also by transesophageal Doppler echocardiography. Ventricular wall motion and pulmonary venous flow pattern were analyzed by transesophageal Doppler echocardiography. The pattern of monophasic forward flow in the pulmonary vein was associated with reduced wall motion during deteriorated cardiac function, while the flow pattern became biphasic as cardiac function recovered. From these results, we concluded as follows: 1. Early decisions as to whether VAD is indicated are important. 2. A right VAD should be considered in cases with biventricular failure, during left ventricular assist, if right atrial pressures elevated more than 18 mmHg constantly. 3. The evaluation of cardiac function by transesophageal Doppler echocardiography is useful for making decisions as to wean patients from a VAD. PMID- 2104422 TI - [Magnetic resonance angiography using a magnetic resonance flow tagging technique]. AB - A direct bolus imaging method, which was developed for flow quantitation, was applied to the cervical regions of four normal volunteers to perform magnetic resonance angiography. A transverse section of 10 mm thickness was selectively excited to tag blood flow in the supraclavicular region and a projected image of the tagged bolus viewed in terms of anteroposterior direction was obtained after the echo time (TE). Like cine magnetic resonance imaging, multiple images representing four to 16 cardiac phases were obtained with repeated excitations. With a relatively long TE, ranging from 50 to 200 msec, we advanced tagged blood farther downstream, so as to elongate the visualized bolus along the vessel. Within the visualized bolus, the outer layer close to the vessel wall, where the blood flow velocity was slow, stretched like long tails behind the central part of the bolus producing arrow-head shapes, and the tails were assumed to represent the vascular structure. Bilateral common carotid and vertebral arteries were visualized in each image size approximately 5 cm obtained at the systolic phase. Since prolonged TE yielded less signal intensity, the bolus was not clearly visualized when TE was longer than 100 msec. The cine display of images with multiple cardiac phases produced good evaluations of dynamic changes of pulsatile flow, and this method is expected to be a useful diagnostic tool which combines the capability of flow quantitation with non-invasive angiography. The accuracy of this method in delineating a stenotic lesion was also evaluated using phantom with steady flow, since it is one of the most important capabilities of a clinically used angiographic method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104423 TI - [Coronary arterial rupture during percutaneous transluminal coronary angioplasty: a case report]. AB - A case who developed rupture in a diagonal branch of the left anterior descending coronary artery (LAD) during percutaneous transluminal coronary angioplasty (PTCA) is reported here. The present case was 80-year-old man with severe focal stenosis of the LAD at its junction with a diagonal branch. PTCA for the LAD lesion was successfully performed, but occlusion of the diagonal branch developed later. A subsequent ECG showed elevation of an ST segment in a VL, and PTCA for the diagonal branch was attempted. A 018 Hi-torque floppy guide wire was introduced into the occluded diagonal branch, and its dilatation was attempted using a 2 mm Simpson-Robert catheter. During a maximal pressure of 120 psi, a deformity was found at the distal end of the balloon. Post-PTCA angiograms showed rupture of the diagonal arterial branch, and mild to moderate pericardial effusion was observed by echocardiography. The patient experienced transient hypotension (60 mmHg at systolic), but his condition gradually stabilized after the administration of only a pressor medication. Neither pericardiocentesis nor emergency surgery was performed. The next day, follow-up angiograms showed diagonal branch occlusion at the proximal portion of the rupture site. His clinical course was satisfactory with spontaneous resolution of pericardial effusion and mild elevation of his cardiac enzymes (CPK = 243IU). In this case, it was concluded that the cause of coronary arterial rupture was the difference in diameters of the coronary artery (1 mm) and the balloon catheter (2 mm). This was the first rupture case experienced among 750 PTCA sites (0.13%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104424 TI - [Congenital anomalies of the coronary arteries with associated ischemic ST depression on exercise: a report of three cases]. AB - This report presented evidence of myocardial ischemia as the etiology of angina pectoris in three patients with congenital anomalies of the coronary arteries but without arteriosclerotic disease. All of three cases showed angina pectoris and ST depressions on their exercise electrocardiogram. Case 1: This 58-year-old man developed angina pectoris at the age of 50 years. His treadmill exercise test precipitated chest pain and ST depression. His coronary arteriograms disclosed an ectopic origin of the right coronary artery just anterior to the origin of the left coronary artery in the left coronary sinus. No significant atherosclerotic stenosis was present. An apparent ischemic manifestation appeared to be caused by compression of an aberrant right coronary artery between the aorta and the right ventricular infundibulum. Case 2: A 49-year-old woman had a history of angina. Her treadmill exercise test induced chest pain and an abnormal exercise electrocardiographic finding. Her coronary arteriograms revealed a single left coronary artery. Insufficient perfusion was postulated as a cause of apparent myocardial ischemia in this case though angiographically, there was adequate perfusion. Case 3: This 31-year-old man had a six-year history of angina. His treadmill exercise electrocardiograms revealed ischemic changes accompanied by chest pain. Coronary arteriograms disclosed a coronary artery fistula. The ischemic manifestation was apparently caused by inadequate perfusion due to coronary steal. With the increasing use of coronary arteriography, unusual origins and courses of coronary arteries will be more frequently encountered. Precise knowledge of anomalies is prerequisite for evaluating variations in the location of the coronary artery ostia and their statistical probabilities. PMID- 2104425 TI - [Tachycardia-induced cardiomyopathy: a case report]. AB - A 30-year-old man with chronic sustained ventricular tachycardia (VT) lasting more than seven years was treated with propranolol, 30 mg/day. This resulted in controlled cardiac rates of 90 to 130/min during sleep, and 100 to 195/min while awake. However, he experienced Adams-Stokes attacks twice, in September and December, 1986. During the second attack, ambulatory heart monitoring showed his VT rate of 212/min. An electrophysiological study revealed that the VT focal point was in the lower-mid region of the interventricular septum in the right ventricle. The VT was characterized by abnormal enhanced automaticity. This VT could not be interrupted either by single or multiple combinations of antiarrhythmic drugs. Cardiac catheterization revealed a diffusely enlarged hypokinetic left ventricle, even at the rate of 120/min VT (EF 27%, C.I. 2.3 l/min/m2). Because of his severe hemodynamic state, we performed electrical catheter ablation successfully. After the ablation, his left ventricular wall motion gradually improved. Nine months after the ablation, his left ventricular diastolic dimension decreased from 64 to 48 mm and the left ventricular systolic dimension decreased from 57 to 28 mm on M-mode echocardiography, while ejection fraction increased from 27 to 73% on the left ventriculography. Bi-ventricular myocardial biopsy specimens obtained prior to the ablation revealed only cellular hypertrophy of varying degrees, and vacuole degeneration consistent with non specific cardiomyopathy. However, nine months after the ablation, these findings were no longer present. Thus, this case was considered tachycardia-induced cardiomyopathy initiated by VT, lasting many years. PMID- 2104426 TI - [Conservative and surgical treatment of pericarditis--our experience]. AB - Methods and results of both conservative and invasive therapy of pericarditis were analysed in the group of 30 patients. An emphasis was on successful treatment of mild (idiopathic) pericarditis and efficiency of the early started, combined pharmacotherapy (tuberculostatics + corticosteroids) of pericarditis of tuberculous etiology. A stress is on marked immediate efficacy of surgery in case of cardiac tamponade, independent on its etiology, with simultaneous recommendation of ultrasound-guided pericardial sac paracentesis. Survival rate in patients with malignant pericarditis is relatively low. PMID- 2104427 TI - [Pericarditis at the Internal Disease Clinic of the Institute of Tuberculosis and Lung Diseases (1981-1987)]. AB - Causes, symptoms, clinical forms, and methods of diagnosis of pericarditis were analysed in a group of 30 patients. Chest pain, dyspnea, and tachycardia were prevailing clinical symptoms of the disease. Particularly useful diagnostic technique is ultrasound, being a method of choice in the diagnosis of the most frequent exudative pericarditis. The most frequent cause of cardiac tamponade was malignant pericarditis. Diagnostic problems with particular reference to tuberculous etiology of pericarditis have also been discussed. PMID- 2104428 TI - [Respiratory metabolism in patients during exercise therapy in the early period of acute myocardial infarction]. AB - Respiratory and cardiocirculatory response to rehabilitation calisthenics in 30 patients, aged 39-66 years, with recent myocardial infarction was studied. Respiratory exchange (Douglas-Haldane method), heart rate, blood pressure, oxygen pulse and electrocardiogram during exercise were investigated. Rehabilitation was performed between the 4th and 21st day of myocardial infarction, in 4 periods with gradually increasing effort, according to the model A designed at the Cardiology Institute in Warsaw. The time of exercises was 10-18 min, depending on the period of rehabilitation. It was found that lung ventilation, tidal volume, oxygen uptake and carbon dioxide output were increased by 20-40% during exercise of the I and II periods of rehabilitation and by 60-100% in the III and IV periods of mobilization. Energy cost of calisthenics rehabilitation was in the lightest case 13 kJ/min. The most increase in respiratory exchange caused exercises performed in sitting position, walking and stair climbing. The last type produced also the highest rise in heart rate (mean 20%) and systolic blood pressure (mean 17% of resting values). PMID- 2104429 TI - [Evaluation of the effect of 6-month ambulatory rehabilitation after myocardial infarction]. AB - A 6-month ambulatory rehabilitation was assessed in 347 patients. Patients classified for therapeutical training have had various degree of the systemic and coronary circulation, values of left ventricle systolic periods. These patients were divided into four groups. Group I consisted of patients with efficient systemic and coronary blood circulation. Group II consisted of patients with efficient systemic circulation and relatively efficient coronary blood flow. Group III included patients with relatively efficient systemic circulation and efficient coronary blood flow. Group IV included patients with relatively efficient both systemic and coronary blood flow. A significant improvement (in all groups) in the systemic and coronary blood flow was seen after a 6-month period of rehabilitation. This improvement was confirmed with polygraphic techniques whereas PWC 170 test was used to evaluate the improvement in physical fitness. PMID- 2104430 TI - [Mitral valve prolapse detected during hemodynamic studies]. AB - To estimate frequency of the posterior mitral valve leaflet prolapse in routinely performed left ventriculography, 1000 consecutive ventriculograms of the right anterior oblique projection were analyzed. A group of patients consisted of 511 women and 489 men at mean age 46,5 years. Clinical diagnosis of heart lesions, myocardial disease, pulmonary hypertension or arrhythmias were indications for hemodynamic studies. In the investigated group of patients, there were no patients with clinical diagnosis of the coronary artery disease. Prolapse of the posterior mitral valve leaflet was diagnosed in 59 patients. Idiopathic mitral valve prolapse was diagnosed in 10 patients. Prolapse of the posterior mitral valve leaflet was most frequent in atrial septal defect (16.6%), myocardial lesion (12.5%), and after mitral commissurotomy (8.9%). Posterior mitral valve leaflet prolapse is not a frequent anomaly in routinely performed left ventriculography. Relatively often occurrence of the mitral valve prolapse in atrial septal defect and only occasional in the aortic lesions and dilated cardiomyopathy seems to point out at a role of the left ventricle size in pathogenesis of this syndrome. PMID- 2104431 TI - [Our experience with using amrinone in circulatory failure]. AB - A study aimed at evaluating an effect of amrinone of blood circulation dynamics (cardiac output), using impedance ++rheography. The study involved patients with acute, congestive cardiac failure (NYHA III-IV degrees). Cardiac output was measured prior to and 3 and 24 hours following amrinone administration. A favourable effect of a 24-hour i.v. infusion of amrinone on blood circulation dynamics was confirmed. The drug proved to be proarrhythmic. PMID- 2104432 TI - [Evaluation of the anti-arrhythmia effectiveness of Phenazolinum Polfa in paroxysmal atrial fibrillation]. PMID- 2104433 TI - [Dissecting aneurysm of the ascending aorta as a late complication of the treatment of acquired defects of the aortic and mitral valves]. AB - A diffuse aneurysm of the ascending aorta was observed five months after prosthetic valve implantation in to mitral and aortic orifices because of the acquired valvular heart disease. The main factor predisposing to the formation of a false aneurysm was an infection of the endocardium and ascending aortal wall which were observed previously during cardiac surgery. The diagnosis, based on the clinical symptoms and non-invasive investigations, was later confirmed with aortography and intra-operatively. PMID- 2104434 TI - [Permanent cardiac stimulation in a patient with isolated dextrocardia and ventricular septal defect]. AB - A case of pacemaker implantation because of acquired atrioventricular block third degree in woman aged 39 years with rare isolated dextrocardia with inversion of cardiac ventricles, compensatory transposition of both aorta and pulmonary artery, and ventricular septal defect. The end of electrode has wedged in the apex of the arterial ventricle. Following pacemaker implantation, patients clinical course of gynaecological operation was uneventful. PMID- 2104435 TI - [Usefulness of echocardiography in the diagnosis of the causes of arterial embolism]. PMID- 2104436 TI - [With what and for what we fight in cardiology]. PMID- 2104437 TI - [Results of the treatment of patent ductus arteriosus]. AB - Since the first effective surgical treatment of PAD, the indications for such a treatment have been more extensive and its results and methods have been changing. We present 123 patients who underwent surgery for PAD in the Clinic of Cardiosurgery, Institute of Cardiology, Medical Academy of Lodz within 1978-1987. In 101 cases PAD was dissected and both ends were sutured in two layers with continuous sutures, and in 22 cases PAD was ligated with 3 ligatures. In 30 patients PAD coincided with other congenital defects of the circulatory system. No cases of recanalization were observed in our patients. One death in the postoperative course was noted. PMID- 2104438 TI - [Subcutaneous injections and intravenous infusion of sodium salt of heparin in the treatment of thrombosis of deep veins of the lower extremities]. AB - Ninety-four patients with deep vein thrombosis of inferior limbs were randomly allocated to receive sodium heparin either by subcutaneous injections or by continuous intravenous infusion for six days. No significant difference was observed in the therapeutic efficiency as judged by phlebographic examinations and in rate of symptomatic pulmonary embolism between the two groups. There was one instance of major bleeding in the subcutaneous group. Minor bleedings occurred in 10 of the 48 patients treated with subcutaneous heparin and in 13 of the 46 patients receiving intravenous heparin. The results showed that subcutaneous injections of sodium heparin are as effective and safe as continuous intravenous infusion of this drug in the treatment of deep vein thrombosis. PMID- 2104440 TI - [Musculo-cutaneous flaps in the reconstruction of the organs after oncological operations in the head and neck areas]. AB - A method of skin-muscular flaps construction is being discussed together with their use for the reconstruction of the organs after oncological surgery of the head and neck. Own experience with the use of such flaps in 83 cases are also discussed. PMID- 2104439 TI - [Various parameters of lipid metabolism after intra-arterial injections of ozone in patients with ischemia of the lower extremities and diabetes mellitus]. AB - In 50 subjects with arteriosclerotic ischaemia of the lower extremities and 41 subjects with diabetes mellitus ozone was applied intra-arterially. Before and after the treatment serum lipids concentration was examined. In the group with arteriosclerotic ischemia significant decrease in cholesterol level and both his fractions was seen. Whereas in the group with diabetes the cholesterol LDL was significantly reduced. In both groups total lipids level serum was decreased. It suggests that ++ozone therapy set back the arteriosclerosis progress, normalized some parameters of lipid metabolism and improved HDL to LDL cholesterol fractions relationship. PMID- 2104441 TI - [Our experience with reconstruction of the breast]. AB - Breast reconstruction in female patients undergoing mastectomy for breast cancer (17 patients) or benign breast disease (2 patients), and malformation of breast due to asymmetry (19 patients) was started in 1983. Mastectomy in 10 patients was performed because of the cancer, and in 17 patients due to benign breast disease. Age of patients ranged from 15 to 58 years. Breast reconstruction was performed within 1-12 years following mastectomy. Two different methods of reconstruction were applied: a) flap graft of patient's own skin and muscle from latissimus muscle of the back with silastic prosthesis implanted under graft (12 breasts), and b) implantation of the prosthesis only (28 breasts). Correction of the opposite breast was also made in 3 patients. No complications are seen up-to date. Esthetic results are also satisfactory. PMID- 2104443 TI - [Evaluation of the analgesic effectiveness of tramadol hydrochloride in surgical practice]. AB - Tramadol hydrochloride was administered to: a) 90 patients who underwent various abdominal surgery (group A) immediately after operation; b) 50 patients with inoperable tumors of pharynx, stomach, pancreas, liver and biliary tract and colon (group B); c) 32 patients in surgical out-patient clinic (group C). Excellent and favourable results (group A - 87.8%; group B - 74%, and group C - 75%) and negligible adverse reactions advocate the use of tramadol hydrochloride both in in- and out-patient surgical clinics as an effective analgesic agent. PMID- 2104442 TI - [Perioperative blood transfusion in patients with malignant neoplasms]. AB - Within 1986-1988, 3,358 patients were treated at the Department of Surgery, Military Teaching Hospital in Bydgoszcz. Hundred twenty six out of these patients were operated for the malignant tumors. Indications to blood transfusion in case of patients with cancer were analysed retrospectively. In our patients about 50% whom blood was given were justified cases. It was found that the analysis of indications based on laboratory findings may decrease the amount of blood given patients who underwent surgery for cancer. PMID- 2104444 TI - [Wegener's granulomatosis]. PMID- 2104445 TI - [Adverse reactions to intravenous contrast media]. PMID- 2104446 TI - [Problem of patient's consent to surgical treatment in life-threatening situations]. AB - A case of a self-injury in a 19-year man is presented. The patient stabbed his thorax with a needle (a wire 9 cm long) which penetrated the right lung near the heart. The patient did not agree to the operation. Left cardiac auricle laceration with hemothorax and pericardial tamponade developed within 13 days. The authors suggest immediate surgery despite patient's disagreeing or even rebel in all situations threatening the lives of the prisoners or convicts. Two ++sub periods might be distinguished in the above mentioned situation: (a) potential, and (b) real life-threat. Surgery should have been performed in the potentially life-threatening ++sub-period in this particular patient. PMID- 2104447 TI - [Implants in reconstructive surgery of the nasal bone]. AB - Development of the conception of using alloplastic materials in restoration of nose skeleton or in completion of its loss was presented in a sketch. Some of the incontemporary implantations were briefly discussed indicating the main advantages and disadvantages in comparison with autogenic implants most often used in similar treatments. PMID- 2104448 TI - [Modeling of implants for filling up defects of the nasal bone]. AB - Our technique of modelling implantations completing the losses of nose skeleton on the basis of before-treatment nose measurement was presented. Depending on the character of distortion two different types of implantations were made, modifying the shape of one of them to achieve better stabilisation in tissues. PMID- 2104449 TI - [Human sparganosis in Ecuador: report of a case in the province of Esmeraldas]. AB - The second case of human sparganosis in Ecuador is reported in a male patient, of an indigenous tribe Chachi, from the province of Esmeraldas, who presented with a nodule localized in the left scapular region. Upon extirpation, a cestode classified as Spirometra was found, but the species could not be determined. PMID- 2104450 TI - [Visceral larva migrans. Report of 3 cases]. AB - We report three cases of children with visceral larva migrans confirmed by enzyme linked immunosorbent assay (ELISA), in Goiania. Pulmonary interstitial infiltrates with dry cough and peripheral eosinophilia characterised the first case. Clinical and laboratorial finding in the second case included dry cough, pulmonary infiltrates, peripheral eosinophilia and hypergammaglobulinaemia. A persistent eosinophilia, between 1987-1989, without apparent cause led to the confirmation of parasite infection in the third case. PMID- 2104451 TI - [Occurrence of kala-azar in the urban area of Grande Belo Horizonte, Minas Gerais]. PMID- 2104452 TI - An unusual relapsing case of skin leishmaniasis. PMID- 2104453 TI - [Inexistence of Piedraia hortae in a Surui indigenous group, Rondonia]. PMID- 2104454 TI - Evaluation of the hemostasis in leptospirosis. PMID- 2104455 TI - Evaluation of the degree of replication of hepatitis B virus in acute and chronic infection. PMID- 2104456 TI - [Prevalence of virus B infection in a hospital community]. AB - The authors studied the prevalence of HBV markers among health care personnel of the University Hospital of the Federal University of Rio de Janeiro. The aim of study was to identify the high risk groups, in order to counsel vaccination of those groups, in order to counsel vaccination of those groups at risk as a routine. As a control group, a group of office workers of the hospital were chosen. A significant difference of incidence of HBV markers, mainly in surgeons (40%) and hemodialysis unit personnel (36.4%) when compared to the control group, was observed (p less than 0.05). The incidence increased with age and the time spent in the profession. The authors concluded that vaccination is indicated in surgeons hemodialysis personnel, dentists and laboratory personnel. PMID- 2104457 TI - [Hospital infections in a high-risk nursery: 2-year analysis]. AB - A prospective study of nosocomial infections in a nursery was undertaken in the Hospital of University of Parana. Infections were identified during a 2 year period from August 1987 to July 1989 with a monthly analysis of prevalence site and agents responsible for nosocomial infections. The biannual mean was 30%. Staphylococcus aureus was the most commonly isolated pathogen. The most common site of nosocomial infections was muco-cutaneous. Educational measures were the most important factor in reduction of nosocomial infection rates. PMID- 2104459 TI - Relegalization of cocaine: a dangerous social experiment? Legislation and drug abuse. PMID- 2104460 TI - Alternative version of steady-state ternary-complex model. Agonist potency, affinity and efficacy. PMID- 2104458 TI - [Frequency of patients with anti-Cysticercus cellulosae blood antibodies in 5 municipalities of the state of Sao Paulo]. AB - Considering the important health public problem that human cysticercosis represents, the frequency of anti-Cysticercus cellulosae antibodies was studied in 1,264 serum samples, 1,064 being from the general population individuals (821 adults and 243 children) living in five municipalities of Sao Paulo State, Brazil; and 200 from patients admitted to the Psychiatric Hospital Bezerra de Menezes (Presidente Prudente). Discs of synthetic fabric-resin with the valently bound were employed for ELISA tests. Among the sera from adults, nineteen (2.30%) were reactive 2 (0.82%) among the children sera. Ten (5.00%) among the psychiatric patients sera presented reactivity. This was significantly higher than that observed for the adults of the general population group (p less than 0.05). PMID- 2104461 TI - Alternatives to animal experimentation: developing in-vitro methods and changing legislation. AB - Despite recent changes in legislation in several countries and general reduction in the use of animals in biomedical research, the impatience of antivivisectionists to see reductions in animal experimentation shows no signs of abating. Gerhard Zbinden analyses the reasons for this continuing dissatisfaction, arguing that real progress has been made in biomedical research, but that the complexities of developing internationally recognized regulations constitute a barrier to rapid change in product safety testing methods. PMID- 2104462 TI - New ligands for L-type Ca2+ channels. AB - Although the clinically important categories of drug represented by verapamil, nifedipine and diltiazem are defined as acting at three major and discrete sites on the L class of voltage-dependent Ca2+ channel, it is likely that some new classes of drug modulate channel activity by acting at additional sites. David Rampe and David Triggle describe the actions of some of these new drugs, which may both offer improved therapeutic and side-effect profiles over existing agents and provide information to define further the structure and function of this channel class. These drugs may mimic the actions of endogenous ligand(s) and such ligands could provide new directions for Ca2+ channel drug structures. PMID- 2104463 TI - Somnogenic activity of immune response modifiers. AB - Sleepiness is a presenting symptom in nearly all infectious diseases. James Krueger describes how microbial products, such as muramyl peptides, lipid A and double-stranded RNA, as well as endogenous products elicited by these substances, such as interleukin 1, modulate sleep. The altered sleep during infection seems to result from an exaggerated activation of physiological sleep mechanisms, since normal sleep is controlled by a wide range of substances including many of these immune response modifiers. PMID- 2104464 TI - Are molecular and electrophysiological data refining models of agonism? PMID- 2104465 TI - Brain 5-HT1A receptor agonism: a novel mechanism for antihypertensive action. PMID- 2104466 TI - Mass spectrometry at high mass: virtues and vices of some new approaches. PMID- 2104467 TI - [Studies on the stereochemistry and structure-activity relationship of cholinolytic compounds 3-(2-phenyl-2-cyclopentyl-2-hydroxyl-ethoxy) quinuclidines]. AB - Four optical isomers of the new cholinolytic compound 3-(2-phenyl-2-cyclopentyl-2 hydroxyl-ethoxy)-quinuclidine (I) have been asymmetrically synthesized by two methods. Method one: Recemic 1-phenyl-1-cyclopentylepoxyethane reacting with 3R or 3S-quinuclidinol produces a mixture of (R-1) and (R-2) or (S-1) and (S-2) respectively. The chemical yields varied from 57% to 78%. The highest % de is 22 and the major product is (R-1) or (S-1). Method two: Grignard reaction of 3R or 3S-benzoyl-methoxy-quinuclidine with cyclopentyl magnesium bromide yields a mixture of (R-1) and (R-2) or (S-1) and (S-2). The chemical yield is 80%. The highest % de is 81 and the major product is (R-2) or (S-2). Preliminary evaluation of the four new optical isomers revealed the following series of biological potencies: (R-2) greater than (I) greater than (S-1) greater than (R 1) greater than (S-2). In the coupling of the compounds with the active centers of M receptors, the absolute configurations in carbon-3 of the quinuclidinyl group and carbon-2 of the substituted ethyl group play an important role. The influence of carbon-2R is greater than that of carbon-3R on cholinolytic potency. PMID- 2104468 TI - [Studies on the active constituents of Momordica charantia L]. AB - Five compounds were isolated from the seeds of Momordica charantia. This paper reports their structure determination by spectral (IR, UV, HNMR, CNMR, and MS) and chemical methods. The structures of I, II, III, IV and V were elucidated as vacine, mycose, 3-O-(beta-D-glucopyranosyl)-24 beta-ethyl-5 alpha-cholesta-7, trans-22E, 25 (27)-trien-3 beta-ol, momorcharaside A and momorcharaside B respectively. Mycose was the first time found in this plant and compound III was the first time found in the genus Momordica. IV and V were new compounds. IV exhibited obvious inhibition of DNA and RNA syntheses in S 180 tumor cells in preliminary pharmacological studies. PMID- 2104469 TI - [Study of the response characteristics of PVC membrane ion-associate type electrodes for organic base cations]. AB - A new type of ISEs which only uses alkaloid precipitants in place of ion pairs as active materials in polyvinyl chloride was recommended. The characteristics of the electrodes sensing over ten kinds of organic bases have been studied in comparison with those based on ion pairs. It can be concluded that the response characteristics of ion-associate type ISEs depend on the strength of the association between ion-exchange site and principal ions. Visual turbidimetry was used to select active materials for ISEs in advance. Among six alkaloid precipitants (silicotungstic acid, tetraphenyl borate, dipicrylamine, picric acid, picrolonic acid and Reineckate), silicotungstic acid is the most active material for ion-associate type organic base cation ISEs. With it, the sensor has wider Nernst linearity and lower detection limit than some ion pair based ones in literature. PMID- 2104470 TI - [Micellar chromatographic study of amines]. AB - Aqueous solutions of the cationic surfactant, hexadecyl-trimethyl ammonium bromide (CTAB), and the anionic surfactant, sodium dodecylsulfate (SDS) were used as mobile phase in HPLC to study the micellar chromatographic retention mechanism of seven amines and weak organic acids with various distribution coefficients and to study the influence of different pH values mobile phase on the solute retention. An exponential model equation for micellar chromatographic retention mechanism was put forward, which gives a reasonable explanation of the effects of electrostatic interaction and hydrophobic interaction between the solute and the three phases (micelle phase, surfactant modified stationary phase and bulk water phase). This equation can be used to estimate the micellar chromatographic retention pattern of the solute. PMID- 2104471 TI - [Use of derivative UV spectroscopy to monitor the percutaneous absorption of befunolol-HCL]. AB - Second-order derivative UV spectroscopy was used to measure the transfer of befunolol-HCl across full-thickness rabbit skin in vitro. The effect of penetration enhancers, azone-PG and PEG-400, on permeation course of befunolol HCl was studied. A type of horizontal diffusion cell was employed. Permeability coefficients were measured in normal saline and in solutions containing the enhancing agents. The results indicated that befunolol-HCl may be an interesting candidate for transdermal administration and azone-PG highly and significantly increases the skin permeation of the drug in the solvent system tested. PMID- 2104472 TI - [Synthesis of 2-formyl (acetyl) substituted quinoline thiosemicarbazones]. AB - A series of 2-formyl (acetyl) substituted quinoline thiosemicarbazones (III, XII, XIII) were prepared in order to evaluate their antimalarial activity. Oxidation of substituted quinolines (IV) with selenium dioxide gave 2-formyl substituted quinolines (V). 2-Acetyl substituted quinoline (IX) was obtained from IV by oxidation, esterification, Claisen condensation and decarboxylation. III1-9 were synthesized by two methods; one was by condensation of 2-formyl (acetyl) substituted quinolines with methyl hydrazinecarbodithioat to form methyl-3-[1-(2 quinolinyl)-alkylidene] hydrazinecarbodithioate (XI), then the S-methyl group of XI was displaced by substituted amines to form the desired substituted thiosemicarbazones. The other was by condensation of 2-formyl (acetyl) substituted quinolines with 4-substituted-3-thiosemicarbazide (X) to afford directly III1-9, III10-12 were obtained by selective reduction of corresponding nitro compounds with stannous chloride and XII as a by-product was obtained by the nonselective reduction of III7 with stannous chloride. 3-Hexyl-4-oxothiazolin 2-yl(2-formyl or acetyl substituted quinoline) hydrazones (XIII1,2) were prepared from III1,4 via cyclization under sodium acetate condition. Eighteen compounds were found to be inactive in mice infected with ANKA strain of Plasmodium berghei. PMID- 2104473 TI - [Chemical identification of structure of podocarpamide by synthesis]. AB - Podocarpamide, isolated from the bark of Zanthoxylum podocarpum Hemsl., is a new compound with platelet aggregation inhibiting and SGPT level lowering activities. Its structure was inferred to have two possible forms, either I or II, from its spectra. The structure of podocarpamide was identified as I by synthesis. PMID- 2104474 TI - [Structure revision of triptophenolide]. AB - A diterpenoid-lactone, white thin crystals, C20H24O3, m/z: 312 (M+), mp 222-223 degrees C, UV lambda max (EtOH) 217 (log epsilon 4.36) nm, has been isolated from the ethyl acetate extract of the roots of Tripterygium wilfordii Hook. f., in a yield of 0.025%. Its structure was elucidated by spectral analysis (UV, IR, MS, 1HNMR and 13CNMR) and X-ray SCD. It is the known triptophenolide with revision of structure. Triptophenlolide was shown to have obvious inhibiting effects on lymphocyte and IgG (P less than 0.01) when mice and rats were given ig 1.5 mg/kg. The total complements in blood serum was increased. When BALB/C mice were given ig 1.5 mg/kg, the ear oedema induced by dimethyl benzene was significantly inhibited (P less than 0.01); The ear oedema induced by croton oil in SD rats at a dose of ig 1.0 mg/kg was also significantly inhibited (P less than 0.05). The vitamin C content of the adrenal gland was reduced in mice at a dose of 1.5 mg/kg. The ig LD50 of triptophenolide was greater than 30 mg/kg. PMID- 2104475 TI - [Determination of ranunculin in Pulsatilla chinensis and synthetic ranunculin by reversed phase HPLC]. AB - A method for the determination of ranunculin in Pulsatilla chinensis and synthetic ranunculin by reversed phase HPLC using betamethasone as internal standard is described. The column employed was a 10 micron LiChrosorb RP-18 (230 x 14 mm), the eluting solvent consisted of methanol-water (40:10, V/V) and the effluent was monitored at 225 nm. The advantages of this method are simple, rapid and accurate. The coefficients of variation are less than 1%. PMID- 2104476 TI - [Adsorptive stripping voltammetry of chlorprothixene at glassy carbon electrode]. AB - A new electrochemical stripping method for measuring the antipsychotic drug chlorprothixene was reported. The drug, which was adsorbed on the surface of glassy carbon electrode, showed a sharp oxidative stripping peak at about +0.7 V (vs. Ag-AgCl) in voltammetry. The response was linear over the 0.01-1 microgram/ml concentration range. The detection limit was 2 ng/ml, about 400 times higher than UV method. The electrode surface was polished with alumina between the measurements to activate the electrode and provide good reproducibility. The open circuit accumulation/medium exchange/stripping voltammetry scheme has been proposed to avoid interference. The method has been used for direct determination of chlorprothixene in tablets and urine samples. PMID- 2104477 TI - [Progress of studies on the chemical constituents of Ganoderma triterpene]. PMID- 2104478 TI - Pharmacokinetics and autoradiography of [3H] or [14C]stepholidine. AB - After iv [3H]stepholidine (SPD) 12 MBq/kg, the concentration-time curve in rats was found to be a two-compartment open model. The distribution phase T1/2 alpha = 3.6 min, the elimination phase T1/2 beta = 168 min. The absorbed radioactivities of [3H] SPD in 15-30 min were 80-87%. The amounts of [3H]SPD bound to plasma protein, liver and kidney homogenates were estimated to be 37, 31, and 30%, respectively. During 3 d after ip [3H]SPD 50 MBq/kg, 56% of the radioactivity was excreted in urine and 5% in feces, thus, it suggested that [3H]SPD was mainly excreted by kidneys. After iv a single dose of [14C]SPD in mice, the whole-body autoradiography showed that [14C]SPD was rapidly distributed among various tissues. High radioactivities were found in kidneys, liver, brain, salivary glands, Harder's glands, heart blood and muscle at 2 min and intensively localized in kidneys and stomach mucosa at 30 min. The radioactivities in these tissues disappeared 4 and 8 h later, while that in intestine could not be detected 24 h later. PMID- 2104479 TI - Ventricular arrhythmia evoked by microinjection of picrotoxin into brain areas in rabbits. AB - To explore the main areas of brain responsible for arrhythmia evoked by icv picrotoxin (Pic), a very small dose of Pic (3 micrograms) was injected into different areas of brain in anesthetized rabbits. The short latency of arrhythmia was found after microinjection of Pic into posterior hypothalamus (PH, 5.6 +/- 0.9 min) and the medial part of tuberal region (7.5 +/- 2.9 min). The ventricular arrhythmia was abolished by vagotomy, iv phentolamine or diazepam, or pretreatment with adrenalectomy or vagotomy. Microinjection of phentolamine or diphenhydramine into PH prior to Pic postponed the arrhythmia. The results indicate that PH and the medial part of tuberal region are the most effective areas for Pic to induce arrhythmia, activations of both sympathoadrenomedullary and parasympathetic systems are involved in the genesis of arrhythmia. PMID- 2104480 TI - [Effects of 7-methoxy-4'-hydroxyl-3'-diethylaminomethylisoflavone on heart atrium and ventricular papillary muscles of guinea pig]. AB - In isolated guinea pig right atria, 7-methoxy-4'-hydroxyl-3' diethylaminomethylisoflavone (MHDF), a new synthetic isoflavone produced noncompetitive antagonisms to isoproterenol- and histamine-induced positive chronotropic actions with pD'2 values of 5.04 +/- 0.10 and 4.90 +/- 0.18, respectively. MHDF inhibited the positive chronotropic response to CaCl2. In isolated left atria, the negative inotropic action of MHDF increased as the frequency increased. In papillary muscles, MHDF 3 mumol/L reduced the contractile force, while Vmax was decreased and APD and ERP were prolonged. These results indicated that the mechanism of MHDF on myocardium is related to inhibition of Ca2+ influx, Na+ influx and K+ efflux, not by blocking beta or H2 receptors. PMID- 2104481 TI - [Effect of nimodipine on the contraction and the Ca influx of rat aorta]. AB - The relaxant effect of nimodipine (Nim) on rat aorta was studied in vitro. Nim inhibited KCl-induced contraction (IC50 = 40 nmol/L) more potently than NE induced contraction (IC50 = 20 mumol/L), but did as equipotently as KCl-induced 45Ca influx (IC50 = 30 nmol/L). There was a positive correlation between inhibiting the KCl-induced 45Ca influx and the contraction (r = 0.98). However, it inhibited the NE-induced 45Ca influx (IC50 = 60 nmol/L) more potently than the NE-induced contraction. Verapamil inhibited the 2 components of NE-induced contraction significantly, while Nim only inhibited the contraction evoked by extracellular Ca2+ influx significantly. Nim did not influence the 45Ca influx into resting cells of rat aorta. These results suggest that the relaxant effect of Nim on rat aorta may be closely related to the blockade of Ca2+ entry through both potential-dependent calcium channels (PDC) and receptor-operated calcium channels (ROC), while the action on PDC seems to play a more important role than that on ROC. PMID- 2104482 TI - [Effects of trihexyphenidyl on basilar artery of rabbits and cerebrovascular circulation of rats]. AB - Trihexyphenidyl (Tri) inhibited the contraction of rabbit basilar artery due to high K+ (45.6 mmol/L). IC50 was 2.9 +/- 0.7 mumol/L. The contractions of basilar and mesenteric arteries due to calcium and those of basilar artery and saphenous vein due to serotonin were noncompetitively. Tri inhibited myogenic activities of the portal vein strips of rats and increased the normal cerebral blood flow of rats to 19 +/- 7 ml/(min.100 g). PMID- 2104483 TI - Electrophysiological effects of m-nisoldipine and nisoldipine on papillary muscles of guinea pig. AB - The effects of m-nisoldipine (m-Nis) and nisoldipine (Nis) on action potentials of papillary muscles in guinea pigs were studied using intracellular microelectrodes. THE RESULTS: (1) APD and Vmaxs in normal papillary muscles were reduced by m-Nis and Nis. However, the APA, Vmaxf and overshoot were not affected. (2) In the partially depolarized papillary muscles, the APA, overshoot, Vmax and APD were depressed in a dose-dependent manner. The inhibitory effects of Nis on APA, APD50 and PPD were greater than those of the m-Nis. (3) There was a good correlation between APD50 and PPD derived from a linear regression. By the linear equation, PPD was easily calculated from APD50. PMID- 2104484 TI - [Effects of benzyltetrahydropalmatine on action potentials of myocardium and transmembrane K+ and Ca2+ currents in Purkinje fibers]. AB - Standard microelectrode and two-microelectrode voltage clamp techniques were used to study the effects of benzyltetrahydropalmatine (BTHP) on action potentials of isolated myocardium and transmembrane K+ and Ca2+ currents in Purkinje fibers. The effect of BTHP 3-100 mumol/L consisted of prolongation of the action potential duration and reduction of delayed rectifier current (Ik) in concentration-dependent manner. At concentration above 200 mumol/L, the contractile force of the isolated myocardium was depressed and in voltage clamp experiments the slow inward current (Isi) was reduced. These results suggest that the inhibition of Ik induced by BTHP was in relation to its anti-arrhythmic action. PMID- 2104485 TI - [Frequency- and voltage-dependent effects of changrolin on maximal upstroke velocity of action potentials in guinea pig papillary muscles]. AB - Changrolin (CRL) is a new antiarrhythmic drug originated in China in 1970s. The effects of CRL on maximal upstroke velocity (Vmax) of action potentials were studied with standard microelectrode and computer in guinea pig papillary muscles. CRL depressed the Vmax. This effect was dependent on the rate of stimulations. The onset of use-dependent depression was monoexponential and dependent on drug concentration and rate of stimulations. The rate of recovery from use-dependent depression also followed a single exponential time course. CRL shifted the curve relating normalized Vmax to membrane potential in the hyperpolarizing direction. The onset rate was 0.156 +/- 0.025 AP-1 (RDB 50%), and offset rate (tau r) was 4.7 +/- 0.9 s. These suggest that CRL belongs to class Ia antiarrhythmic drugs. PMID- 2104486 TI - [Effects of superoxide dismutase on ischemic reperfusion injury in isolated working heart and cultured myocardial cells of rats]. AB - An isolated working rat heart underwent 40 min of normothermic ceasing perfusion and 25 min of reperfusion. Superoxide dismutase (SOD) or/and mannitol were added to the perfusate 15 min before ceasing perfusion and 15 min after reperfusion. The results indicate that SOD (37,000 IU/L) improved significantly the contractile function of heart and increased the aortic output and coronary flow. Mannitol 0.02 mol/L provided additional benefit. The rat myocardial cells were cultured in the medium for 3 h with hypoxia followed by 2 h of reoxygenation. The content of lactic dehydrogenase (LDH) in the medium was increased and the degree of fluorescence polarization of myocardial cell membrane was raised. SOD was effective in preventing LDH release and decreasing the degree of fluorescence polarization. These results clearly demonstrate that ischemic reperfusion are capable of causing significant myocardial injury, which can be reduced or prevented by administration of oxygen free radical scavenger SOD. PMID- 2104487 TI - [Effects of schizandrin B and schisanhenol on drug metabolizing-phase II enzymes and estradiol metabolism]. AB - Intragastric gavage of schizandrin B (Sin B) and schisanhenol (Sal) 200 mg/kg once daily for 3 d significantly increased liver glutathione-S-transferase (GSH-S T) and microsomal cytochrome P-450 in mice and rats. Sin B and Sal antagonized the increase of uterus weight induced by sc estradiol in ovariectomized, and decreased serum estradiol level in mice. RIA and HPLC showed an enhancement in [3H] estradiol metabolism by liver microsomes from Sin B- and Sal-treated mice. The results indicated that both Sin B and Sal have inductive actions on drug metabolizing-phase I and phase II enzymes in mice and rats. PMID- 2104488 TI - Effects of platelet-activating factor on rat mesenteric microcirculation. AB - The actions of platelet-activating factor (PAF) on rat mesenteric microcirculation were studied by laser Doppler microscopy in vivo. PAF 0.2 -0.6 micrograms/kg iv produced a dose-related decrease in the blood flow velocity and an increase in the diameters of the mesenteric arterioles and venules. These responses were completely reversed by pretreatment with PAF receptor antagonist SRI 63441. The results suggest that PAF may be a mediator of microcirculatory disturbances in the disease conditions associated with excessive PAF release. PMID- 2104489 TI - [Inhibitory effect of dauricine on platelet activating factor released from calcimycin-induced mouse peritoneal macrophages]. AB - The effects of dauricine (Dau) on the release of platelet activating factor (PAF) from mouse peritoneal macrophages stimulated by calcimycin (A-23187) was studied. The method of sodium [3H]acetate incorporating into macrophages to synthesize PAF was set up for the first time. Calcimycin (0.2 mumol/L) significantly induced mouse peritoneal macrophages to utilize sodium [3H]acetate to synthesize PAF. PAF released from macrophages medium fluid increased as the concentration of sodium [3H]acetate increased. The maximal amount of PAF released from macrophages was attained by incubating macrophages with sodium [3H]acetate (250 mumol/L) and calcimycin (2 mumol/L) over 30 min. Extracted by CHCl3:CH3OH:H2O (2:2:1.8), separated by thin layer chromatography (TLC) and determined by liquid scintillation counting, PAF released was inhibited significantly by Dau both in time (10-30 min) and dose (1-1000 mumol/L) dependent manners. The IC50 of Dau for the formation of PAF was 2.5 mumol/L. On the same condition PAF release was also significantly inhibited by quinacrine at 500 mumol/L. The results indicate that Dau is a potent inhibitor of PAF synthesis in mouse peritoneal macrophages. PMID- 2104490 TI - Enhancement of T lymphocyte proliferation and suppression of antibody producing cell formation by methionine-enkephalin. AB - Methionine-enkephalin (met-enk) 0.1-100 nmol/L significantly enhanced lymphocyte proliferation induced by T cell mitogens. On the other hand, the peptide markedly inhibited splenocyte blastogenesis induced by B cell mitogen lipopolysaccharides (LPS) and sheep red blood cell (SRBC)-driven plaque-forming cell (PFC) formation in vitro. Met-enk alone had no effect on immune responses. However, naloxone 50 nmol/L had also a stimulating effect on Con A-induced splenocyte proliferation. The similar results were also observed in vivo. The results also indicated that the enhancement of T cell function by met-enk was stronger in immunosuppressed mice than in the normal mice. PMID- 2104491 TI - [Tissue schizontocidal action and acute toxicity of trifluoroacetyl primaquine]. AB - Trifluoroacetyl primaquine (M-8506), 6-methoxy-5-trifluoroacetyl-8-(4-methyl butyl-amino)-aminoquinoline oxalate, synthesized by the Institute of Parasitic Diseases was compared with primaquine for tissue schizontocidal action and acute ig LD50. In P yoelii sporozoite infected mice, the protection rates with ig M 8506 5, 10 and 20 mg (base)/kg on the day of infection were 56.7, 87.2 and 100%, respectively. These were comparable to the protection rates with primaquine 5, 10 and 20 mg(base)/kg (54.4, 90.8 and 100%, respectively). The radical curative effect was conducted in P cynomolgi sporozoite infected Macaca mulatta. Since im pyronaridine 10 mg/kg b.i.d. (6 h apart) completely eliminated the parasites in monkeys infected with erythrocytic stages of P cynomolgi, the tissue schizontocidal activities of M-8506 and primaquine were observed by im administration of pyronaridine 10 mg/kg b.i.d. on d 1. M-8506 at 0.75, 1.5 and 3 mg/(kg.d) x 3d plus pyronaridine were given to 7, 4 and 2 infected monkeys with parasitemia respectively. All the monkeys, except one receiving 0.75 mg/(kg.d) x 3 d, were radically cured. Primaquine 0.75, 1.5 and 3 mg/(kg.d) x 3 d were administered to 3, 3 and 2 monkeys respectively. Two monkeys receiving primaquine 0.75 mg/(kg.d) x 3 d relapsed on d 42. The parasitemia reappeared earlier than that treated with M-8506 0.75 mg/(kg.d) x 3 d and relapsed on d 62. Because M 8506 is less toxic than primaquine in mice and more effective in radical treatment of simian malaria, further studies on trifluoroacetyl primaquine are worthy to be considered. PMID- 2104492 TI - Growth inhibition in vitro of Mycobacterium smegmatis by ten N-aryl glycyl hydrazides. AB - N-(4-amino-2-nitro-toluinyl) glycyl hydrazide and N-(biphenyl) glycyl hydrazide partially inhibited the growth of M smegmatis at 20 micrograms/ml and showed a total inhibition at 100 micrograms/ml. Replacement by a nitro or halogen group lowered the activity. PMID- 2104493 TI - [Effects of Phytolacca acinosa polysaccharides I on cytotoxicity of macrophages and its production of tumor necrosis factor and interleukin 1]. AB - The in vivo effects of Phytolacca acinosa polysaccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied. PEP-I 80, 160 mg/kg was given ip twice every 4 d. Both doses were found to have significant enhancing activity on macrophages cytotoxicity against S180 sarcoma cells and malignant transformed fibroblast L929 cells. Peritoneal activated macrophages were incubated with LPS for 2 and 24 h to induce TNF and IL-1, respectively. The TNF and IL-1 activities were tested from cytotoxicity against L929 cells in an absorbance assay of enzymatic reaction and proliferation of thymocytes co stimulated assay separately. The optimal time for TNF production was found on d 8. Significant increases in TNF and IL-1 were observed. In comparison of the effect of PEP-I on TNF with that of known priming agent BCG, there was no difference between these two, but PEP-I had a high effect on IL-1. These results suggest that cytotoxicity of macrophages primed by PEP-I is closely related to its TNF and IL-1 production. PMID- 2104494 TI - [Effects of 10-hydroxycamptothecin on induced chromosome aberrations in Chinese hamster ovary cells and micronuclei in mouse bone marrow and fetal liver]. AB - 10-Hydroxycamptothecin (HC) is a new antitumor principle isolated from Camptotheca acuminata indigenous to China. The genetic toxicity of HC was assessed by mouse bone marrow and transplacental micronucleus test as well as Chinese hamster ovary cell chromosomal aberrations. All of these tests showed positive results. The highest rate of chromosomal aberrations was 83% at 0.125 microgram/ml for 48 h. The number of micronucleated polychromatic erythrocytes in bone marrow of mice was remarkably increased in 19.8% cells at 12.5 mg/kg for 24 h. The micronucleus formation was most often seen at 16 h after im HC in fetal liver and 24 h in maternal bone marrow. The peaks were 36 +/- 19 and 31 +/- 10%, respectively. The results from in vivo and in vitro suggest HC is a mutagen, furthermore, a transplacental mutagen in mouse. PMID- 2104495 TI - Potential role of SH groups in the radiosensitivity of adenylate cyclase. AB - The role of oxidation of SH groups in the activity of adenylate cyclase and in radiosensitivity of the enzyme was investigated. Adenylate cyclase activity was measured in purified membrane preparation of 19 day old chicken embryo brains. N ethyl-maleimide (NEM) and lead-acetate were used as SH inhibitors. Gamma irradiation was carried out with 60-Co source. NEM inhibition of adenylate cyclase was dose dependent and 50 per cent inhibition was observed at 40-50 microM NEM. Activity of adenylate cyclase was elevated at lower concentrations of lead-acetate (10 nM-100 microM) and was inhibited at higher concentrations (above 100 microM). The presence of 40 microM NEM did not alter the shape of lead acetate saturation curve of adenylate cyclase. Gamma irradiation in the dose range of 100-800 Gy elevated the adenylate cyclase activity measured in the presence of 5 mM NaF but did not alter the basal activity. Gamma irradiation did not have significant effect on NEM saturation of adenylate cyclase, while it altered slightly the lead acetate saturation curve. PMID- 2104496 TI - Bidirectional compartmental approximation of realistic nerve cell structures. AB - Passive electrotonic activity of anatomically complex nerve cells has been computed through a simplified anisotropic "smoothing" of the original structures. The algorithm for this "smoothing" involves a recursive matching of the amplitude, zero and pole of the input impedances for each segment. This algorithm can be used for both spatially and/or electrically inhomogeneous cables. The directional sensitivity of the voltage transfer in non-smooth dendrites has been characterized by a decomposition which reveals the bidirectional segmentation of the core geometry according to the opposite wave fronts of electronic potentials in dendrites. The impedance diagrams can be used to estimate the goodness of the whole procedure in the frequency domain. The bidirectional segmentation of the core geometry may serve as a basis of the compartment simulations of those excitable nerve cells where the voltage spread is modulated by irregular dendritic structures, such as spines. PMID- 2104497 TI - Three-dimensional presentation of tissue oxygenation parameters. AB - From the Fick equation comes that VO2 = DO2 x O2ER, where VO2--oxygen consumption, DO2--oxygen delivery, O2ER--oxygen extraction ratio. These 3 factors can be represented in one figure using the fy = fx x fz equation. This equation spans a surface representing all the possible movements and relationships of tissue oxygenation parameters, helping in this way to evaluate the problems of tissue oxygenation more precisely. PMID- 2104498 TI - Neonatal treatment with phenobarbital, zixoryn and chloramphenicol lack of imprinting effect of zixoryn on microsomal enzyme activities. AB - Two potent microsomal enzyme inducing agents, phenobarbital and flumecinol (Zixoryn) as well as the microsomal enzyme inhibitor chloramphenicol (Chlorocid) were given subcutaneously to newborn rats in the first 5 days of their life. Microsomal cytochrome P-450 and b5 content and various cytochrome P-450 and P-448 dependent enzyme activities were measured at the age of 20 weeks. Phenobarbital had positive imprint effect on aminopyrine N-demethylase activity in female and on aniline hydroxylase activity in male rats. Flumecinol had no imprint effect. Chloramphenicol had a positive imprint on aniline hydroxylase activity in male rats. Sex differences in microsomal enzyme activities were not affected by the xenobiotics used. PMID- 2104499 TI - Effect of free radicals in ischaemic renal failure in the dog. AB - After a 30-minute control period ischaemia was evoked in dogs under Nembutal (30 mg/kg, i.v.) anesthesia, by clamping the left renal artery for 45 minutes. This was followed by a 90-minute reperfusion period when diuresis, GFR, PAH clearance, sodium and potassium excretion, malondialdehyde level in the plasma of the renal vein and SOD enzyme activity of the erythrocytes in renal venous blood were determined. Besides the control group (n = 6), the following treated groups were investigated: 1. Allopurinol (n = 7) in a dose of 100 mg/kg, given orally for two days, 2. Silibinin (n = 6) in a dose of 4 mg/kg/hour, given into the renal artery, 3. MTDQ-DS (n = 6) in a dose of 150 mg/kg/hour, given intravenously. 4. SOD (n = 4) 4 mg infusion (initiated 1 minute prior reperfusion). In the first 15 minute period following reperfusion GFR was 21%, cPAH 29% and sodium and potassium excretion 67 and 42% of the values of the contralateral kidney, respectively. Renal function improved gradually during the 90 minutes of reperfusion, and the above-mentioned parameters reached 59, 57, 65 and 76% of the corresponding control data. Increase of malondialdehyde level in the venous blood of the kidney during reperfusion might have been indicative of the production of free radicals; the difference, however, was not significant statistically. The administrations did not lead to considerable change in any of the parameters investigated. No difference could be demonstrated by histological methods between the kidneys of the treated and untreated animals. The compounds studied are thought to be free radical scavengers; in the present work, however, no protective effect could be demonstrated. PMID- 2104500 TI - Diaphragmatic fatigue in the rat. AB - We studied fatigue of rat diaphragm in response to repetitive brief and prolonged electrical stimulation of the phrenic nerve, at 0.2, 1-100 Hz. Low and high frequency of stimulation produced twitch and tetanic contractions in the rat diaphragm. A mean maximum twitch tension of 1.4 +/- 0.1 g was produced at 1 Hz, and a mean maximum tetanic tension of 5.6 +/- 0.3 g was obtained at 100 Hz (means +/- S.E., n = 8). Twitch and tetanic fatigue was produced at all frequencies of stimulations, but with different time scale, or duration, and with different number of stimuli delivered to the muscle. At low rates of stimulation, e.g. 10 Hz, fewer stimuli were needed to fatigue the muscle (3000 in 5 min), whereas at high rates of stimulation, e.g. 50 Hz, more stimuli were needed to fatigue the muscle (6600 in 2.2 min). The amplitude of the tetanic tensions elicited at 10 and 50 Hz, at the end of 5 or 2 min fatiguing stimulation, was 39 +/- 2.7% and 80 +/- 3.1% of their respective control tensions (2.8 +/- 0 2 g and 5.3 +/- 0.5 g, n = 8, P 0.001). It was concluded that fatigue in the rat diaphragm depended on the frequency and duration of stimulation as well as on the number of stimuli delivered to the muscle. Various mechanisms of muscle fatigue are described in the discussion to explain the observations made in the present investigation. PMID- 2104501 TI - Anticariogenic effect of fluoridated milk and water in rats. AB - The aim of the study was to get further experimental data on the anticariogenic effect of sodium fluoride (NaF) when administered in milk or water. Thirty six weanling Osborne-Mendel rats were divided into two experimental groups (A, B) of 12 rats each and two control groups (C, D) of six rats each. During the experimental period of four weeks all animals were superinfected with Strep. mutans (NCTC 10449), kept in an automatic feeding machine and given a cariogenic diet (MIT 301). Group A received sodium fluoride (NaF) in water (15 ppm) and group B in ultra high temperature treated milk. Groups C and D respectively received plain milk and distilled water. Group A did not show significantly lower caries reduction compared with the control groups. Group B had significantly the lowest caries scores compared with all other groups. Scores in group C (plain milk) were lower than those in groups D (plain water). The results suggest that the anticariogenic effect of NaF is more pronounced when the vehicle is milk instead of water. PMID- 2104502 TI - Update 90: avoiding needle-stick injuries. PMID- 2104503 TI - Let's all play by the same rules! PMID- 2104504 TI - Intraepidermal type VII collagen. Evidence for abnormal intracytoplasmic processing of a major basement membrane protein in rare patients with dominant and possibly localized recessive forms of dystrophic epidermolysis bullosa. AB - Of 84 patients with dystrophic forms of epidermolysis bullosa consecutively enrolled in the National Epidermolysis Bullosa Registry, four were noted by indirect immunofluorescence with the LH 7:2 monoclonal antibody to have granular basilar keratinocyte intracytoplasmic deposits, rather than exclusively linear basement membrane deposits, of type VII collagen. Indirect immunoelectron microscopy demonstrated that these deposits were primarily perinuclear, although lesser amounts were also detectable between tonofibril bundles, within hemidesmosomes, and within and beneath the lamina densa. In two patients the mode of transmission was autosomal dominant; in two others the inheritance pattern was unknown. Whereas widespread lesions were present at birth, in each case blistering ceased within the first year of life, reminiscent of the findings in transient bullous dermolysis of the newborn. We interpret these laboratory findings as indicative of the presence of a defect in the intracytoplasmic packaging or in the transport of type VII collagen within basilar keratinocytes. PMID- 2104505 TI - Destiny rides again as twins overeat. PMID- 2104506 TI - Tretinoin for the treatment of cutaneous graft-versus-host disease. AB - Chronic graft-versus-host disease (GVHD) of the skin is a common complication of allogeneic bone marrow transplantation. It can be resistant to common methods of systemic immunosuppression. We report successful treatment of a patient with progressive cutaneous GVHD that was resistant to cyclosporine and steroids after allogeneic marrow transplantation for acute myelogenous leukemia using topical tretinoin (Retin-A). PMID- 2104507 TI - Trauma and seronegative spondyloarthropathy. PMID- 2104508 TI - Cranial gunshot wounds. AB - Cranial gunshot wounds frequently produce devastating injuries to central nervous system structures. This article reviews pertinent principles of ballistics to explain several mechanisms of injury to the brain. A series of 21 consecutive cases of cranial gunshot wounds is presented outlining a protocol for management and identifying factors of prognostic significance. PMID- 2104509 TI - High blood alcohol levels in women. PMID- 2104510 TI - Dissociative symptoms in relation to childhood physical and sexual abuse. AB - Studies have reported high rates of childhood abuse in people with psychiatric illness. This study examined whether dissociative symptoms are specific to patients with histories of abuse. Ninety-eight female psychiatric inpatients completed self-report instruments that focused on childhood history of trauma, dissociative symptoms, and psychiatric symptoms in general. Sixty-three percent of the subjects reported physical and/or sexual abuse. Eighty-three percent had dissociative symptom scores above the median score of normal adults, and 24% had scores at or above the median score of patients with posttraumatic stress disorder. Subjects with a history of childhood abuse reported higher levels of dissociative symptoms than those who did not. PMID- 2104511 TI - Organization of the monocyte/macrophage system of normal human skin. AB - Monocytes and macrophages are known to be important for a variety of functions; however, whereas epidermal Langerhans cells have been studied in great detail, few data are available for the dermal monocyte/macrophage system. Therefore we investigated the density, distribution, and phenotype of dermal macrophages in normal human skin using a panel of monoclonal antibodies for single and double labeling. We demonstrate here that within normal human dermis macrophages reside with a remarkable density. Principally, these cells exhibit the phenotype of the phagocytic macrophage system (CD11c+, KiM8+), whereas members of the immune phagocyte system (CD11c+, KiM8-) are absent from normal dermis with the exception of a few Langerhans cells in the papillary body. Within the dermal phagocytic macrophage system we uncover an unexpected phenotypical and morphologic heterogeneity, which correlates with the tissue localization. This study provides a basis for investigating the participation and change of the dermal macrophage system in cutaneous disorders. PMID- 2104512 TI - On duplicate publication of a manuscript. PMID- 2104513 TI - A pertussis vaccine myth dies. PMID- 2104514 TI - Mercury and crematorium chimneys. PMID- 2104515 TI - Time-related predictors of suicide in major affective disorder. AB - The authors studied 954 psychiatric patients with major affective disorders and found that nine clinical features were associated with suicide. Six of these- panic attacks, severe psychic anxiety, diminished concentration, global insomnia, moderate alcohol abuse, and severe loss of interest or pleasure (anhedonia)--were associated with suicide within 1 year, and three others--severe hopelessness, suicidal ideation, and history of previous suicide attempts--were associated with suicide occurring after 1 year. These findings draw attention to the importance of 1) standardized prospective data for studies of suicide, 2) assessment of short-term suicide risk factors, and 3) anxiety symptoms as modifiable suicide risk factors within a clinically relevant period. PMID- 2104516 TI - Short-term morbidity and mortality of implantation of automatic implantable cardioverter-defibrillator. AB - Over the 3-year period from Jan. 1, 1986, through Dec. 31, 1988, we have implanted 101 automatic implantable cardioverter-defibrillators into patients with life-threatening ventricular arrhythmias. There were 82 male patients and 19 female patients. The mean age was 58 years with a range of 25 to 82 years. The indication for implantation was ventricular fibrillation in 89 patients and recurrent ventricular tachycardia in 12 patients. Seventy-seven patients had a history of prior myocardial infarction or coronary artery disease, or both. Eighteen patients had nonischemic cardiomyopathy. One patient had a prolonged QT syndrome and five patients had no evidence of preexisting structural heart disease. The mean injection fraction was 37% +/- 17%. Forty-one of the automatic implantable cardioverter-defibrillator implantations were associated with procedures necessitating cardiopulmonary bypass. The hospital mortality rate was 4% and the morbidity rate was 15%. The only statistical difference between those patients who did and did not have postoperative complications was a history of a prior myocardial infarction (90% versus 54%, p less than 0.05). Twenty percent of patients had new-onset postoperative atrial fibrillation after implantation of the device. Eleven percent of patients had sustained ventricular tachycardia postoperatively. Although there was a trend toward a higher complication/death rate in the patients whose automatic implantable cardioverter-defibrillator was inserted in association with cardiopulmonary bypass (24% versus 15%) and the occurrence of new-onset postoperative atrial fibrillation (27% versus 15%), these findings were not statistically significant. Automatic implantable cardioverter defibrillator implantation with and without concomitant cardiopulmonary bypass is associated with a clinically important morbidity and mortality rate and development of postoperative arrhythmias. PMID- 2104517 TI - Management of interstitial pregnancy. PMID- 2104518 TI - Long-term follow-up of adult AML patients. PMID- 2104519 TI - Prolonged weakness after extended mechanical ventilation in a child. PMID- 2104520 TI - Perivascular location and phenotypic heterogeneity of microglial cells in the rat brain. AB - Employing immunohistochemical techniques and a panel of monoclonal antibodies that recognize rat cells of monocyte/macrophage lineage, we have demonstrated that cells labeled with these antibodies are widely distributed throughout the parenchyma of the rat brain. These cells have a remarkable microglial morphology and form phenotypically heterogenous populations. Double immunoperoxidase staining with the monoclonal antibody and anti-von Willebrand factor antiserum, which recognizes vascular endothelial cells, revealed that these cells are located exclusively at perivascular sites in the adult brain. These observations indicate that the microglial cells are perivascular cells of the monocyte/macrophage lineage, and may be intimately involved in various immunopathogenic conditions of the central nervous system. PMID- 2104521 TI - Which anti-smoking programme? PMID- 2104522 TI - Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood. AB - The role of the local synthesis of thrombin in platelet recruitment and thrombus stabilization in heparinized blood was examined in vitro. Mural thrombosis was visualized and measured in a thin, rectangular, collagen-coated capillary under controlled rheological conditions by using fluorescence digital videomicroscopy and fluorescence microphotometry. Thrombin activity was inhibited in heparinized blood by the synthetic competitive inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone (FPRCH2Cl), resulting in a marked reduction in the rate of platelet accumulation on collagen surfaces, indicating a role for thrombin in platelet recruitment. Similar although lesser effects were observed by reducing thrombin synthesis with antibodies to factors II and X. To decouple the role of thrombin in platelet recruitment by direct stimulation of platelet activity from its role in thrombus stabilization via fibrin formation, thrombosis was measured in heparinized blood treated with the tetrapeptide glycyl-prolyl-arginyl-proline, which inhibits fibrin monomer assembly into fibrin. The ultimate level but not the initial rate of platelet accumulation was reduced markedly, indicating a role for fibrin in thrombus stabilization against hemodynamic forces. Scanning electron micrographs demonstrated fibrin stands in the heparinized control samples but not in the heparinized samples with glycyl-prolyl-arginyl-proline. These results demonstrate a role for the local action of thrombin synthesized on the surfaces of thrombi even under conditions when the thrombin exerts no bulk effect, such as under heparin anticoagulation. Furthermore, this role appears to be a result of both platelet recruitment and thrombus stabilization. PMID- 2104523 TI - Topography of the retinal thickness in normal subjects. AB - A noninvasive method has been developed that is capable of providing quantitative thickness profiles of the retina. The method was used to map the retinal thickness in five normal human volunteers and determine the reproducibility of the measurements. The reproducibility or equivalent sensitivity of the measurements to detect changes was found to be 5% or 19 microns on the same day and 8% or 31 microns on different days. By averaging the values obtained in five normal subjects, ranging in age from 21 to 43 years (mean, 34 years), a preliminary normal baseline was derived for the thickness profile at the fovea and the thickness cross-section from the optic disc to the fovea. The results of the study indicated that this noninvasive method promises to be of clinical use in diagnosing ocular diseases that produce changes in the thickness of the retinal as well as in monitoring the effectiveness of therapy. PMID- 2104524 TI - False positive IgM-rubella enzyme-linked immunoassay in three first trimester pregnant patients. PMID- 2104525 TI - National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy. AB - This consensus report focuses the presentation, pathophysiology, and management of the hypertensive disorders of pregnancy expanding on recommendations first presented in 1988 by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Practicing physicians should determine whether a patient's hypertension during pregnancy falls into the classification of (1) chronic hypertension, (2) preeclampsia, (3) preeclampsia superimposed on chronic hypertension, or (4) transient hypertension. The distinction, for management considerations, is made between hypertension that is present before pregnancy (chronic and preexisting) and that occurring as part of the pregnancy-specific condition preeclampsia. When maternal blood pressure reaches diastolic levels of 100 mm Hg or greater, treatment should be instituted to avoid hypertensive vascular damage. The report includes a discussion of antihypertensive therapy specific to the chronic or acute hypertension occurring concomitantly with pregnancy. The roles of calcium supplementation and low-dose aspirin to prevent preeclampsia and chronic and transient hypertension are under investigation. PMID- 2104526 TI - [Delayed postanoxic encephalopathy after strangulation--the serial neuroradiological and neurochemical studies]. AB - A 13-year-old boy was the victim of a strangulation attempt. His behavior was normal by the 6th day after the assault. However, from the 7th day, he developed choreoathetosis, dystonia and marked pseudobulbar palsy. CT and T2-weighted MRI at this time revealed a low density and high signal intensity in the region of the bilateral putamen and caudate respectively for the first time. Thereafter, these symptoms and changes in CTs and MRIs subsided gradually over two months. Sequential analysis of CSF for GABA and dopamine during illness revealed reciprocal changes each other with normal recovery. Because of delayed onset of neurological changes, and findings of CSF with reversible symptoms the delayed encephalopathy after strangulation is probably related to biochemical alteration secondary to anoxia in vulnerable basal ganglia. PMID- 2104527 TI - Cortisol production rate in childhood and adolescence. AB - We studied the daily cortisol production rate in 33 normal children and adolescents, using a stable isotope-dilution technique employing high-performance liquid chromatography-mass spectrometry. Two indwelling intravenous catheters were inserted and tracer 9,12,12-2H3-cortisol (deuterated cortisol) was infused continuously for 30 hours. After 6 hours of tracer infusion to allow for equilibration, blood was obtained every 20 minutes for 24 hours. The mean (+/- SD) cortisol production rate was 9.5 +/- 2.5 mg/day (6.8 +/- 1.9 mg/m2/day). Cortisol production rate did not vary with sex or pubertal stage. These results suggest that the cortisol production rate in children and adolescents is significantly lower than previously estimated. PMID- 2104528 TI - Complications during spinal anesthesia in infants: high spinal blockade. PMID- 2104529 TI - Effect of surface electrode position on the compound action potential evoked by ulnar nerve stimulation during isoflurane anaesthesia. AB - The effect of surface electrode positioning on the evoked compound action potential was studied during isoflurane anaesthesia without neuromuscular block. In 20 ASA I-II patients (age 36-50 yr), the response after supramaximal ulnar nerve stimulation was analysed with a neuromuscular relaxation monitor (Relaxograph, Datex) and with a memory recorder. Seven pairs of surface recording electrodes were compared: (1) adductor pollicis muscle vs second finger; (2) adductor pollicis m. vs first finger; (3) first dorsal interosseus m. vs second finger; (4) abductor digiti minimi m. vs fifth finger; (5) adductor pollicis m. vs second dorsal metacarpal; (6) abductor digiti minimi m. vs fourth dorsal metacarpal; (7) thenar vs hypothenar. Steady biphasic response was recorded with electrode pairs 1-4. Marked variation and low amplitude existed at pairs 5-7. Peak-to-peak amplitude at pair 3 was the greatest (12.5 (SD 3.7) mV) compared with pair 4 (9.4 (SD 2.0) mV) and pair 1 (8.5 (SD 2.0) mV). A close correlation between the amplitudes and integrated areas was found. The first dorsal interosseus muscle response was optimal and the electrodes were simple to fix; this site may be recommended for clinical monitoring. PMID- 2104530 TI - Regional anaesthesia must be properly managed. PMID- 2104531 TI - Treatment of scars and keloids with a cream containing silicone oil. AB - The clinical effect of silicone cream containing 20% of silicone oil was tested on 47 patients with hypertrophic scars and keloids. A silicone cream/occlusive dressing technique, quite similar in manner to silicone gel treatment, resulted in a remarkable improvement of scars and keloids in 9 of 11 cases (82%) whereas the simple application of the cream onto the scars and keloids of 36 cases resulted in only mild improvement in 8 (22%). Using the chi-square test, a statistically significant difference was seen between these two treatments (p less than 0.01). From these findings, we suggest that occlusion and hydration are the principal modes of action of the silicone gel sheet method and our silicone cream/occlusive dressing technique. PMID- 2104532 TI - Weak calf syndrome. PMID- 2104533 TI - Restoration of forearm rotation following malunited fractures: Baldwin's operation. AB - The technique and results of a series of 38 Baldwin's operations (excision of the ulnar neck) are described. This is a simple and effective procedure to restore forearm rotation following malunited fractures of the distal forearm. PMID- 2104534 TI - Readmission rates. PMID- 2104535 TI - Lung hypoplasia and polyhydramnios found in association with congenital diaphragmatic hernia. PMID- 2104536 TI - Inhalation carcinogenesis of N-nitrosomorpholine (NMOR) in rats and hamsters. AB - N-Nitrosomorpholine (NMOR) is a potent liver carcinogen in rats when administered orally. NMOR was found in the atmosphere at working places in the rubber industry in concentrations up to several hundred micrograms/m3. It can be assumed that NMOR inhalation may play a role in human carcinogenesis. Therefore an inhalation study was carried out to evaluate the carcinogenic potency of NMOR vapors in rats and hamsters. The concentration of volatile NMOR in the inhalation chamber was continuously determined with a Thermal Energy Analyzer. The rats received 29 administrations (4th/day, 5 days/week; mean inhaled daily dose: 130 micrograms/animal; total dose: 15 mg/kg bodyweight). The hamsters inhaled a total of 38 mg/kg of NMOR (21 applications, daily dose 260 micrograms/animal). In rats 4 carcinomas and 5 neoplastic nodules of the liver, 1 neuroblastoma and 1 mucoepidermoidal carcinoma of the nose, and 1 carcinoma of the thyroid gland were induced. In treated hamsters 4 carcinomas of the liver, 2 neurogenic sarcomas of the nasal region, and 5 papillomas of the trachea were found. None of these tumors were observed in control rats and control hamsters. PMID- 2104537 TI - Phase I and clinical pharmacological evaluation of a parenteral hexamethylmelamine formulation. AB - Hexamethylmelamine has been evaluated in single agent and combination regimen studies for many years, but only following p.o. administration. Pharmacological studies in animals and humans have shown that systematic availability of parent drug following p.o. administration is relatively low and variable due to extensive first-pass metabolism rather than due to poor absorption. Two Phase I clinical trials, with accompanying pharmacokinetic studies, have been conducted by using a parenteral formulation in which hexamethylmelamine was prepared by Intralipid 10%. The parenteral formulation was well tolerated by all patients receiving hexamethylmelamine by 1-day and by daily for 5-days schedules. Nausea and vomiting were the dose-limiting toxicities. Maximally tolerated doses on the 1-day and daily for 5-days schedules were approximately 850 mg/m2 and 630 mg/m2/day, respectively. No responses were observed in either study. Following i.v. administration of 540 mg/m2 hexamethylmelamine, plasma elimination was best described by a three-compartment open model with terminal half-life, total body clearance, and steady-state volume of distribution values of 10.4 h, 0.75 liter/min/m2 and 460 liters/m2, respectively. Twenty-four h urinary recoveries of parent drug were less than 1% for all patients. Accumulation of hexamethylmelamine during the 5-day treatment at 945 mg/m2 suggested possible saturation of parent drug elimination at that dose. Phase II studies are currently under way with the parenteral formulation of hexamethylmelamine. PMID- 2104538 TI - Enhanced poly(adenosine diphosphate ribose) polymerase activity and gene expression in Ewing's sarcoma cells. AB - Ewing's sarcoma (ES) is a highly malignant childhood bone tumor and is considered curable by moderate doses of radiotherapy. The addition of chemical inhibitors of the activity of the nuclear enzyme poly(adenosine diphosphate ribose) [poly(ADPR)] polymerase to ES cells in culture results in increased cell killing, a phenomenon called "inhibitor sensitization." Since poly(ADPR) polymerase is thought to be associated with DNA repair, it has been suggested that ES cells and other inhibitor-sensitized cells may have a reduced capacity for polymer synthesis resulting in deficient postirradiation recovery. We present here the unexpected observation that in comparison to other cell lines tested, ES cells exhibit a high enzyme activity, higher constitutive levels of the protein, and elevated levels of its mRNA transcript for poly(ADPR) polymerase. No gross amplifications or rearrangements of the gene were observed; however, regulation of poly(ADPR) polymerase in these tumor cells takes place at the level of the gene transcript. PMID- 2104539 TI - Changes in c-myc and c-fos expression in a human tumor cell line following exposure to bifunctional alkylating agents. AB - This study was initiated to determine if DNA-damaging chemotherapeutic agents can suppress the expression of oncogenes. The effects of three structurally related bifunctional alkylating agents on the steady state mRNA levels of c-myc, c-fos, N ras, and beta-actin in the human colon carcinoma cell line Colo320HSR were examined. Colo320HSR has an amplified c-myc oncogene, which is highly overexpressed, and is assumed to be one of the transforming genes of this cell line. Two concentrations of mechlorethamine, L-phenylalanine mustard, and 4 hydroperoxycyclophosphamide, which produced 1 or 3 log cell kills were used to examine the effects of drug exposure on the expression of specific genes. Steady state mRNA levels were measured by Northern blot analysis. Following a 1-h drug exposure, RNA was isolated from cells at 0, 6, 12, and 24 h following drug removal. The agents used produced changes in the expression of specific genes, and all three did so in a similar fashion. Immediately following drug removal, the steady state expression of c-myc in treated cells was increased 2- to 3-fold compared to control. At 6 and 12 h following drug removal, c-myc levels were depressed 2.5- to 5-fold. By 24 h, c-myc expression approached, but remained below, control levels. Immediately following drug removal, c-fos levels were increased 3- to 4-fold, and from 6 to 24 h following drug removal, c-fos levels gradually return to, or fell below low basal levels. During the 24-h time course, drug treatment had little or no effect on the steady state levels of N-ras or beta-actin. These data support the hypothesis that alkylating agents may suppress the expression of specific transforming genes. PMID- 2104540 TI - Ritanserin decreases portal pressure in conscious and unrestrained cirrhotic rats. AB - We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonist void of systemic effects, caused a significant reduction of portal pressure in conscious cirrhotic dogs. The mechanism by which ritanserin lowers portal pressure is poorly defined. We investigated the splanchnic and systemic hemodynamic effects of ritanserin (0.63 mg/kg body wt i.v., a dose known to completely inhibit binding of 5-hydroxytryptamine to its receptors), in conscious and unrestrained cirrhotic rats (n = 13). Heparinized catheters were placed into the portal vein, inferior vena cava, aorta, and left ventricle with exit from the neck. Hemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabeled microspheres and the reference sample method. Sixty minutes after administration, ritanserin caused a significant reduction of portal pressure ( 17%) with minimal changes in portal venous inflow (+3%). Portal vascular resistance decreased significantly (-23%), whereas splanchnic arteriolar resistance was similar before and after ritanserin. A significant increase in mean arterial pressure (+5%) and cardiac output (+22%) was observed. Our results suggest that ritanserin lowers portal pressure through a mechanism separate from portal venous inflow. This effect could be due to changes in intrahepatic or on portocollateral resistances, or both. These findings support the potential use of this new agent in the treatment of portal hypertension. PMID- 2104541 TI - Sensitivity of serum apolipoprotein A-IV levels to changes in dietary fat content. AB - The distinctive biological properties of apolipoprotein A-IV suggest that its concentration in serum should be specifically regulated by dietary triglyceride. To test this hypothesis, serum lipids, lipoprotein cholesterol, and apolipoprotein levels were measured in 10 normolipidemic male subjects whose dietary fat intake was isocalorically modified over a range of 10%-50% of total calories. Serum apolipoprotein A-IV levels changed significantly from baseline in response to each dietary modification. Apolipoprotein A-IV levels decreased by 21% during the first week of the low-fat (10%) diet, increased to 12% over baseline during the first week of the moderate-fat (25%) diet, and increased further to 35% over baseline during the first week of the high-fat (50%) diet. Unexpectedly, during the second week of each dietary period, apolipoprotein A-IV levels demonstrated statistically significant trends back toward baseline, which were opposite in direction and proportional in magnitude to the changes during the first week. Nonetheless, serum apolipoprotein A-IV levels, but not apolipoprotein A-I or apolipoprotein B levels, were significantly and positively correlated with the percent of total daily caloric intake ingested as dietary fat. It was concluded that serum apolipoprotein A-IV levels are extremely sensitive to acute changes in dietary fat content and over the range of fat intake examined in this study are significantly correlated with the percent of total calories consumed as dietary triglyceride. Furthermore, the results also suggest that apolipoprotein A-IV may be subject to a rapidly acting autoregulatory mechanism. PMID- 2104542 TI - Effects of misoprostol on cell migration and transit in the dog stomach. AB - Prostaglandins of the E series increase stomach mucosal mass by inducing hyperplasia, which could be the result either of increased cell production or of decreased cell loss. This report describes an investigation of the effect of the prostaglandin E1 analogue, misoprostol, on cell migration and transit. 3H thymidine was used to label those cells synthesizing deoxyribonucleic acid in dogs that had been given an oral dose of 300 micrograms/kg per day misoprostol for 11 weeks. The animals were killed at timed intervals, and tissue from the gastric fundus was prepared for autoradiography. The distribution of labeled cells at various times after labeling was used to follow the movement of the wave of label and to calculate median cell migration rates and transit times. The migration rate of cells toward the gastric lumen was significantly increased from 1.4 +/- 0.3 to 3.6 +/- 0.6 cell positions per day in the misoprostol-treated group (p less than 0.001); however, the gland length (from the most basal mucous neck cell to the luminal surface) was also increased (from 52.1 +/- 1.1 to 74.0 +/- 1.6; p less than 0.001), thus there was no significant difference in the (transit) time taken for cells to reach the top of the gland (control, 17.5 +/- 9.8 days; test, 12.2 +/- 7.1 days). PMID- 2104543 TI - Degradation of thyrotropin-releasing hormone and luteinising hormone-releasing hormone by enzymes of brain tissue. AB - In this article, the enzymes of brain and associated tissues that can degrade thyrotropin-releasing hormone (TRH) and luteinising hormone-releasing hormone (LH RH) are reviewed. As both TRH and LH-RH are considered to act as neurotransmitters or neuromodulators in the CNS, attention is paid to the subcellular location of the enzymes described and how their topographies and substrate specificities fit them to playing roles as inactivating agents for TRH and LH-RH or as regulators of intracellular concentrations of TRH and LH-RH. Consideration is also given to enzymes involved in biotransformation of TRH to secondary metabolites that exhibit biological activity and to enzymes involved in the metabolism of secondary metabolites. PMID- 2104545 TI - Research seems to be gaining upper hand on what's been called non-A, non-B hepatitis. PMID- 2104547 TI - Cost-effectiveness and the future of medicine. PMID- 2104544 TI - Synthesis of the membrane fusion and hemagglutinin proteins of measles virus, using a novel baculovirus vector containing the beta-galactosidase gene. AB - An improved baculovirus expression vector was developed to expedite screening and facilitate oligonucleotide-directed mutagenesis. This vector contained twin promoters derived from the P10 and polyhedrin genes of Autographica californica nuclear polyhedrosis virus. The P10 promoter directed the synthesis of beta galactosidase, whereas the polyhedrin promoter controlled the synthesis of foreign gene products. These two genes recombined with wild-type virus genome to yield recombinants which were polyhedrin negative, produced the foreign gene product, and formed blue plaques when beta-galactosidase indicator was present in the agarose overlay. An origin of replication derived from M13 or f1 bacteriophage was also included in the plasmid to permit the synthesis of single stranded DNA. This template DNA was used to introduce or delete sequences through the process of site-specific mutagenesis. The measles virus virion possesses a membrane envelope which contains two glycoproteins: the hemagglutinin (H) and membrane fusion (F) proteins. The H polypeptide has receptor-binding and hemagglutinating activity, whereas the F protein mediates virus penetration of the host cell, formation of syncytia, and hemolysis of erythrocytes. Genes for these two glycoproteins were inserted into the NheI cloning site of the modified expression vector described above. The vector and purified wild-type viral DNA were introduced into Sf9 insect cells by calcium phosphate precipitation. A mixture of wild-type and recombinant virus was generated and used to infect Sf9 cells, which were subsequently overlaid with agarose. After 3 days, 0.1 to 1% of the plaques became blue in the presence of beta-galactosidase indicator. At least 70% of these blue viral colonies contained the foreign gene of interest as determined by dot blot analysis. Recombinant virus was separated from contaminating wild-type virus through several rounds of plaque purification. Insect cells were then infected with the purified recombinants, and synthesis of H and F proteins were verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot detection and Coomassie blue staining. Glycosylation of the proteins appeared to be impaired somewhat, and the precursor to the F protein was not completely cleaved by the proteases present in insect host cells. On the other hand, both proteins appeared to be active in hemagglutination, hemolysis, and cell fusion assays. Levels of synthesis were in the order of 50 to 150 mg of protein per 10(8) cells. PMID- 2104546 TI - From the National Institutes of Health. PMID- 2104548 TI - Epidemiology of hepatitis C virus. A preliminary study in volunteer blood donors. AB - In a survey carried out from 1985 through 1986, volunteer blood donors to The Greater New York Blood Program were tested for two surrogate markers for non-A, non-B hepatitis--elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen. Stored serum samples from selected donors were also recently tested for antibody to hepatitis C virus (anti-HCV). Anti-HCV was detected in 0.9% to 1.4% of donors and was higher in black and Hispanic donors than in white donors. Anti-HCV prevalence increased with increasing age through the fourth decade of life, but decreased thereafter, possibly reflecting the disappearance of detectable antibody with time. Anti-HCV correlated with both alanine aminotransferase level and the presence or absence of antibody to hepatitis B core antigen. These associations suggest that donor screening for elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen was, as expected, at least partially effective in preventing transfusion-associated non-A, non-B hepatitis. The detection of anti-HCV in donors who have neither an elevation of alanine aminotransferase level nor presence of antibody to hepatitis B core antigen suggests that donor screening for anti-HCV will further reduce the risk of transfusion-associated hepatitis. PMID- 2104550 TI - CO2 laser safety. PMID- 2104549 TI - Non-A, non-B hepatitis and antibody to hepatitis C virus. AB - Stored serum samples from the Transfusion-transmitted Viruses Study in the 1970s were tested for the presence of antibody to hepatitis C virus (anti-HCV). Single specimens from five control subjects who did not receive transfusions tested negative for anti-HCV. Of four control subjects who did not receive transfusions and who developed non-A, non-B (NANB) hepatitis after hospitalization, three remained anti-HCV negative; the fourth person with postoperative NANB hepatitis tested anti-HCV positive before the operation. Five transfusion recipients with posttransfusion hepatitis B virus infection remained seronegative; a sixth with NANB hepatitis as well as hepatitis B virus infection had seroconversion for anti HCV. Five of nine transfusion recipients with NANB hepatitis had anti-HCV seroconversion. These results show that present anti-HCV testing demonstrates an etiologic basis for approximately half of the cases of transfusion-associated NANB hepatitis, particularly those that develop chronicity. Although cases of NANB hepatitis without seroconversion may be explained otherwise, they may be caused by another, presently unidentified, virus. PMID- 2104551 TI - Comparison of the erbium-yttrium aluminum garnet and carbon dioxide lasers for in vitro bone and cartilage ablation. AB - The in vitro bone- and cartilage-ablation characteristics of the solid-state erbium:yttrium aluminum garnet laser were compared to those of the carbon dioxide laser. Ablations of fresh, frozen cadaver septal cartilage and maxillary sinus bone were performed using total energies between 1 and 6 J. Specimens were studied using hematoxylin and eosin stain and digitized, computer-assisted measurements of 35-mm photographs. Erbium-yttrium aluminum garnet-ablated bone averaged 5 microns of adjacent tissue thermal injury, compared with 67 microns with carbon dioxide-ablated bone. Erbium-yttrium aluminum garnet-ablated cartilage averaged 2 microns of adjacent tissue thermal injury, compared with 21 microns with the carbon dioxide-ablated cartilage. The tissue-ablation characteristics of the erbium-yttrium aluminum garnet laser are promising for future otolaryngologic applications. PMID- 2104553 TI - Percutaneous feeding gastrostomy in patients with head and neck tumors: a 5-year review. AB - Since the beginning of this decade major advances have taken place in the alimentation of patients with tumors of the head and neck. Gauderer and Ponsky described a percutaneous method of gastrostomy and, in 1983, a number of radiologists, including the senior author, described a percutaneous radiologic method using the Seldinger technique to create a feeding gastrostomy. This method is ideally suited for patients with advanced tumors of the head and neck because it requires neither endoscopy nor general anesthesia. Over the past 5 years, 55 patients with tumors of the head and neck have undergone this procedure. Eighty one percent of the patients had advanced disease at initial presentation. One patient (1.8%) had a procedure-related death and another patient (1.8%) had a complication that required a laparotomy. Three patients (5.4%) had minor complications that required minimal medical attention. None of the patients required general anesthesia and an endoscopy was not required. Patient discomfort during the procedure was minimal. PMID- 2104552 TI - Analysis of gender differences in the auditory brainstem response. AB - This study examined the effects of hormones, head size, and oral temperatures on latencies and amplitudes of the auditory brainstem response in 10 young women, 10 young men, and 5 postmenopausal women. Significant gender differences between men's and women's auditory brainstem responses were confirmed. Men showed longer latencies and smaller amplitudes than women. Results showed that oral temperature has little effect on auditory brainstem response latencies and amplitudes. Head size affects waves III, V, and the amplitude of wave V, but is not entirely responsible for the gender latency difference. By examining young women with normal monthly hormonal cycles, significant changes in the absolute latencies of wave V were observed. These changes were correlated with hormonal changes as measured from venous blood samples. It was concluded that the etiology of the gender difference is a combination of hormonal and head-size differences. PMID- 2104554 TI - Primary extracranial meningiomas of the head and neck. AB - Extracranial meningiomas comprise approximately 2% of all meningiomas. Primary extracranial meningiomas are even less common. This report details our experience with these unusual tumors from 1972 to 1989. The diagnosis, surgical management, and significant histopathologic features are discussed. The correlation of primary extracranial meningiomas with neurofibromatosis type II and a treatment algorithm are presented. PMID- 2104555 TI - Update: Salmonella enteritidis infections and grade A shell eggs--United States, 1989. PMID- 2104556 TI - Unintentional methyl bromide gas release--Florida, 1988. PMID- 2104557 TI - Nonprotein caloric requirements for patients with pancreatic abscess as measured by indirect calorimetry. AB - Few data exist regarding nutritional assessment during pancreatic abscess. We compared nonprotein caloric requirements calculated by Harris-Benedict equation and measured by indirect calorimetry in patients with pancreatic abscess. Seven patients with pancreatitis and pancreatic abscess had determinations of resting energy expenditure via Medicor metabolic cart with 20% added for activity. Caloric requirements were also estimated using the Harris-Benedict equation with stress factors. Determinations from indirect calorimetry ranged from 22.4-46.8 (mean 36.1) kcal/kg/d. Harris-Benedict calculations with stress factor 1.7 differed from indirect calorimetry by at least 15% in seven of ten determinations. Stress factor 1.9 results overestimated indirect calorimetry by over 25% in four of ten determinations. Energy requirements via indirect calorimetry of some patients with pancreatic abscess cover a wide range and do not correlate with Harris-Benedict calculations. Harris-Benedict equation with a stress factor of 1.9 may estimate adequate nonprotein calories for hyperalimentation, but there is risk of overfeeding. PMID- 2104558 TI - Investigation of plasma von Willebrand factor and circulating platelet aggregating activity in mitomycin C-related hemolytic-uremic syndrome. AB - We have studied the ability of the plasma to induce aggregation of both homologous and heterologous platelets in four patients with hemolytic-uremic syndrome (HUS) associated with chemotherapy with mitomycin C (MMC). Neither platelet aggregation was elicited by patients' plasmas nor the in vitro addition of purified von Willebrand factor (vWF) had any effect on the aggregation pattern. In addition, ristocetin-induced binding of patients' vWF to formaldehyde fixed platelets was normal, and multimeric vWF analysis revealed a normal structure of patients' plasmatic vWF whatever the clinical stage in which it was studied. These findings suggest that, in spite of the existence of common clinical and biological features in the various forms of HUS, the pathogenesis of MMC-related HUS may be, at least in part, different from that of the other forms of HUS in which both platelet-aggregating activity and alterations in the vWF are found. PMID- 2104559 TI - Thrombocytopenic purpura in a patient with lupus anticoagulant: requirement of both immunosuppressive and antithrombotic therapies. AB - A 33 year old woman with severe thrombocytopenic purpura complicated by typical lupus anticoagulant developed repeated spontaneous abortion, deep venous thrombosis, and cerebral thrombosis. The platelet count fluctuated from 4,000 to 400,000/mm3 during the 13 year clinical course. The physical and laboratory findings at the time of severe thrombocytopenic purpura were compatible with the criteria of idiopathic thrombocytopenic purpura except for positive lupus anticoagulant. Both immunosuppressive therapy with prednisolone and antithrombotic therapy with warfarin and aspirin were necessary for the control of bleeding and venous and arterial thrombosis. PMID- 2104560 TI - Promoting the art of the possible in long-term care. PMID- 2104561 TI - Intracranial hemorrhage after use of tissue plasminogen activator for coronary thrombolysis. AB - Tissue plasminogen activator (tPA), an approved coronary thrombolytic agent, can cause serious bleeding. We report the cases of six patients with intracranial hemorrhage after tPA treatment for acute myocardial infarction. None of the patients were hypertensive at admission, and only one was hypertensive during therapy. Intravenous tPA, 100 mg, was followed by continuous intravenous heparin infusion; intracranial hemorrhage occurred between 2 and 14 hours after tPA infusion ended and between 3 and 17 hours after heparin therapy was started. The partial thromboplastin time (PTT) was excessively prolonged (from 81 s to more than 150 s) in all patients at onset of intracranial hemorrhage. The intracerebral hematomas were predominantly of lobar location, and two patients had multiple simultaneous hemorrhages. Four patients died from massive intracranial hemorrhage; the mechanism for these hemorrhages was unclear. Factors possibly related to hemorrhage include a systemic fibrinolytic state or a platelet anti-aggregant effect produced by tPA and enhanced hemorrhagic tendency caused by the combined effects of tPA and heparin. Local vascular changes at the bleeding site remain as potential contributing factors for isolated intracranial hemorrhage. PMID- 2104562 TI - Hypophosphatemia complicating management of acute severe asthma. PMID- 2104563 TI - Behavior modification for physicians' practices. PMID- 2104564 TI - Efficiency and cost-effectiveness of advanced EMS in West Germany. AB - A model study was performed by an economist in Lower Frankonia (a mostly rural area of West Germany with several urban centers) to examine the efficiency and cost-effectiveness of the emergency medical service that included prehospital physician presence. To perform this examination about $3.5 million were spent to improve organization and communication within the local emergency medical service, to purchase additional equipment and further emergency vehicles, and to install prehospital emergency physician service. The median response time was lowered to 6 minutes. This report surveys whether these reforms and extra fundings were beneficial and cost-efficient. PMID- 2104565 TI - Of historical interest. General Grant fights cancer. PMID- 2104566 TI - Leukemia among children in a suburban community. 1963. PMID- 2104567 TI - Two decades of reach to recovery: a tribute to the volunteers. PMID- 2104568 TI - Hoxsey Method/Bio-Medical Center. PMID- 2104569 TI - Cancer statistics, 1990. PMID- 2104570 TI - Secondary hematologic neoplasm after intravesical chemotherapy for superficial bladder carcinoma. AB - Two cases are reported of patients who developed a hematologic malignancy several years after intravesical chemotherapy of superficial bladder cancer with etoglucid, doxorubicin, and mitomycin C. In one patient, karyotypic abnormalities (-5, 7q-) typical of a therapy induced malignancy were associated with rapid progression of a refractory anemia with excess blasts in transformation to an acute non-lymphocytic leukemia. Intravesical chemotherapy may be associated with a risk of secondary malignancy. PMID- 2104571 TI - Definitive radiation therapy in the management of symptomatic patients with optic glioma. Survival and long-term effects. AB - We reviewed 24 children who had symptomatic gliomas that involved the optic chiasm and were treated with definitive radiation therapy from 1971 to 1986. In eight patients (33%), histologic confirmation of low-grade astrocytoma was obtained. Patients had radiation therapy only if there was evidence of visual deterioration or other clinical or radiographic evidence of disease progression. Radiation doses ranged from 4500 to 5660 cGy (median, 5400 cGy) with up to a 17 year follow-up period (median, 6 years). The 6-year actuarial freedom from disease progression and overall 6-year survival are 88% and 100%, respectively. Visual improvement or stabilization was seen in 21 (91%) patients after radiation. A high incidence of endocrine abnormalities is reported, with 15 of the 18 patients evaluated after treatment showing growth hormone deficiency. We conclude that definitive radiation therapy is associated with tumor control in most of the patients with progressive optic chiasm gliomas. However, neuropsychiatric and endocrine abnormalities are significant problems that need additional evaluation in these children. PMID- 2104572 TI - Continuous hyperthermic peritoneal perfusion for the treatment of peritoneal dissemination in gastric cancers and subsequent second-look operation. AB - A total of 31 patients with gastric cancer showing peritoneal dissemination received continuous hyperthermic peritoneal perfusion (CHPP) in combination with the administration of cisplatin (CDDP) and mitomycin C (MMC). The authors developed a new special device named the peritoneal cavity expander (PCE) for sufficient perfusion and direct temperature measurement in the peritoneal cavity. As complications of CHPP three patients presented with bone marrow suppressions (leukocytes less than or equal to 3000/mm3 and/or platelets less than or equal to 30,000/mm3): one, leakage of intestinal anastomosis; one, intestinal perforation; and one, acute renal failure. But none of them was lethal. Twelve of 31 patients who had received CHPP during the initial operation underwent second-look operation (SLO) for the assessing the effects of CHPP and for resecting residual or recurrent tumors. Among 12 patients who received SLO complete response (CR) was observed in four patients, partial response (PR) in one, no change (NC) in three, and progressive disease (PD) in four, with the overall response rates (%CR + %PR) standing at 41%. Two-year survival rate of the complete and partial responders was 50%, which was significantly higher than 0% of the other responders (NC + PD). The survival curves of the two groups were significantly different (P less than 0.05, generalized Wilcoxon test). These results supported that CHPP was well tolerated and effective for the treatment of patients with peritoneal dissemination in gastric cancer when combined with anti-cancer drugs having synergism with hyperthermia. Since the outcome of SLO was one of prognostic factors it was important to follow up these patients by SLO. PMID- 2104573 TI - A guide to fragile sites on human chromosomes. AB - This is a guide to 107 fragile sites, all those considered at the most recent International Workshop on Human Gene Mapping, HGM 9.5, held in 1988. The chromosome band locations of all 107 fragile sites are given, together with their gene symbols, frequency, mode of induction, and status. The majority of these fragile sites are common ones induced to expression by aphidicolin. Fragile sites are nonrandomly distributed within the genome. Chromosome 3 is especially short of known fragile sites. Chromosome 21, the chromosome triplicated in Down syndrome, has no known fragile sites. PMID- 2104574 TI - Caries experience in the deciduous dentition as predictor for caries in the permanent dentition. AB - The present study aims at determining a reliable screening test for the prediction of caries. In order to identify children at risk of caries, individual classifications were recorded for 268 children at the age of 7 years, according to different screening criteria of the caries experience in the deciduous dentition and according to caries increment as validation criterion. In order to determine the best screening criterion, ratios of sensitivity, specificity and false-positive and false-negative ratios were computed and plotted in receiver operating characteristic curves. The best screening criterion at less than or equal to 4 dmft resulted in a sensitivity ratio of 0.69, specificity of 0.72 and diagnostic power of 0.78 for caries increment in the permanent dentition at the age of 7-11 years. The potential of the screening is elucidated with an example, showing that 48% of the expenses needed for a preventive treatment for all children could be saved by selecting children at risk with the aid of a screening test. The disadvantage of this decision making is that 19% of the children who develop caries would not benefit from the preventive treatment. PMID- 2104575 TI - The role of human interleukin-6 in B-cell isotype regulation and differentiation. AB - Human Interleukin-6 (IL-6) is a cytokine secreted by T cells, as well as a variety of other cell types, which exhibits B-cell differentiating activity. The recent cloning of the gene that codes for this molecule has allowed us the opportunity to study the function of this molecule alone and in conjunction with other lymphokines in human B-cell isotype-regulation and differentiation. Recombinant human IL-6 enhances immunoglobulin (Ig) M and G secretion by B-cells activated by Staphylococcal A Cowan strain (SAC) and enhances IgM, IgG, and IgA secretion by B-cells activated by pokeweed mitogen. IL-6 also augments immunoglobulin secretion of differing isotypes from various Epstein-Barr Virus transformed B-cell lines. However, IL-6 does not alter the secreted isotype of naive surface IgM-positive B-cells. As human T-cells secrete other lymphokines in association with IL-6 after activation we examined the interaction of Interleukin 2 (IL-2) gamma-interferon (IFN-gamma) and Interleukin-4 (IL-4) with IL-6 on B cell immunoglobulin secretion. IL-2 and IL-4 synergized with IL-6 in augmenting immunoglobulin secretion by SAC-activated B-cells. IFN-gamma significantly inhibited the Ig secretion of SAC-activated B-cells cocultured with IL-6 alone or in combination with IL-2. These results demonstrate that human recombinant IL-6 augments immunoglobulin secretion of isotype-committed B-cells but it does not induce a change in the isotype secreted. In addition, this lymphokine synergizes with IL-2 and IL-4 in supporting Ig secretion. However, IFN-gamma significantly inhibits IL-6 induced Ig secretion. PMID- 2104576 TI - A homogeneous population of lymphokine-activated killer (LAK) cells is incapable of killing virus-, bacteria-, or parasite-infected macrophages. AB - Previous reports have suggested a role for natural killer (NK) cells in directly lysing host cells infected with bacteria and other intracellular microorganisms. Here, we determined the inability of a highly homogeneous population of lymphokine activated killer (LAK) cells to kill macrophages infected with the following intracellular parasites: Mycobacterium avium, Listeria monocytogenes, Legionella pneumophila, Toxoplasma gondii, and Trypanosoma cruzi. In parallel cytotoxicity assays, LAK cells lysed the tumor targets YAC-1 and P815 effectively. Furthermore, we were able to demonstrate that influenza-specific cytotoxic T lymphocytes (CTL), but not LAK cells, were efficient killers of influenza virus-infected macrophages. PMID- 2104577 TI - Biological effect of interferon-gamma during the course of experimental infection of rat by Schistosoma mansoni. AB - We demonstrate here that a second mechanism of platelet activation dependent on lymphokine could also take place in the expression of platelet cytotoxicity against Schistosoma mansoni in vitro. Indeed, IgE, as previously described, but also IFN-gamma, present in the sera of infected rats, together induce platelets from normal rats into cytotoxic effectors for the parasitic larvae. This second mechanism appears also effective in vivo since the passive transfer of normal platelets treated by recombinant IFN-gamma (rIFN-gamma) and the administration of rIFN-gamma to rats conferred a protective immunity to S. mansoni. PMID- 2104578 TI - An assessment of the effects of swainsonine on survival of mice injected with B16 F10 melanoma cells. AB - Systemic administration of swainsonine, an indolizidine alkaloid, inhibits the experimental metastasis of B16-F10 murine melanoma cells. This activity can be attributed primarily to swainsonine-mediated enhancement of host natural killer cell activity. As one next step towards investigating the potential therapeutic utility of this drug, its efficacy in enhancing host survival in the same B16-F10 model system has been assessed. In studies employing intravenously injected tumor cells, pretreatment of mice with swainsonine-containing drinking water provided a reproducible protective effect for the host. This prolongation of survival was substantially enhanced when swainsonine was administered in combination with either of two other immunomodulators, polyinosinic: cytidylic acid (poly-IC) or interleukin-2. In studies in which combinations of these agents were administered after intravenous injection of tumor cells, or after subcutaneous implantation, a greatly reduced effect on host survival was observed. However, when used in combination with cyclophosphamide (to block the effects of suppressor T cells), swainsonine did increase mean survival time. The implications of these results for the use of swainsonine in treatment of metastatic or localized disease, together with its potential mechanism(s) of action, are discussed. PMID- 2104579 TI - Relapsing post-hepatitis aplastic anemia. Immunosuppressive therapy. AB - A 20-month-old Hispanic male developed severe aplastic anemia after an episode of non-A, non-B hepatitis. Prompt and complete recovery of all hematopoietic cell lines occurred after treatment with antithymocyte globulin (ATG) and high-dose corticosteroids. Severe aplasia recurred two months later coincident with a mild upper respiratory infection. A second course of immunosuppressive therapy was followed by complete, sustained improvement. The authors' experience provides clinical evidence indicating that immunologic mechanisms are important in the treatment of severe post-hepatitis aplastic anemia. Children in whom aplastic anemia recurs after immunosuppressive treatment may respond to a second course of therapy. PMID- 2104580 TI - Extracorporeal membrane oxygenation and cerebral blood flow velocity in newborn infants. AB - Doppler ultrasound was used to study cerebral hemodynamics in the pericallosal artery of 21 newborn infants undergoing extracorporeal membrane oxygenation (ECMO) for intractable respiratory failure. Cerebral blood flow velocity waveforms were obtained pre-ECMO, after every major change in cardiopulmonary bypass flow during ECMO, and post-ECMO. The mean pulsatility index (PI) pre-ECMO was slightly higher than after decannulation, secondary to hypocarbia pre-ECMO. The PI decreased significantly at high (61 to 120 ml/min.kg) cardiopulmonary bypass flows. This was associated with an increase in mean arterial pressure, but not with changes in Hct, PaO2, or PaCO2. A negative curvilinear relationship between the amount of cardiopulmonary bypass flow and PI was found. These data suggest an increase in cerebral blood flow velocity and vasodilation of the cerebral vessels at high cardiopulmonary bypass flows, and may explain the occurrence of intracranial hemorrhage in infants undergoing ECMO. PMID- 2104581 TI - Peritoneal dialysis for acute renal failure: overfeeding resulting from dextrose absorbed during dialysis. AB - Peritoneal dialysis is a relatively safe and effective form of therapy for acute renal failure (ARF). As dextrose in the dialysate provides the osmotic gradient to achieve fluid removal, frequent exchanges with dialysate containing high dextrose is occasionally used to achieve negative balance in fluid overloaded patients. It has previously been shown that dextrose absorption from the peritoneal cavity is significant. Using indirect calorimetry and analyzing the dialysate effluent for its dextrose concentration, we studied the effects of high dextrose-containing dialysate in five patients with ARF. Despite minimal intake of calories, all patients had an RQ greater than 1.0 consistent with net lipogenesis resulting from dextrose absorbed from the peritoneal cavity. Four of five patients absorbed greater than 500 g of dextrose over 24 h. As overfeeding could lead to hepatic steatosis, increased CO2 production with worsening of respiratory failure, and hyperglycemia, the risks of using high dextrose containing dialysate fluids should be weighed carefully against potential benefits. When nutritional support is indicated in such patients, contribution of dextrose calories from dialysate fluid should be taken into account. PMID- 2104582 TI - Relationship of plasma cholesterol level to doses of branch-chain amino acids in sepsis. AB - Plasma cholesterol levels, plasma lactate, and total body RQ were measured in septic patients undergoing total parenteral nutrition (TPN) with glucose, fat, and two different branch-chain amino acid admixtures (49% BCAA and 16% BCAA). Mean plasma cholesterol for all measurements (2.61 +/- 0.94 [SD] mmol/L) was lower than normal; however, it was higher with 49% BCAA than with 16% BCAA (2.94 +/- 0.95 vs. 2.27 +/- 0.81 mmol/L, p less than .001) for comparable loads of glucose, fat, and total amino acids. Plasma lactate and RQ were lower with 49% BCAA than with 16% BCAA (p less than .001 for both). Cholesterol was directly related to the absolute dose of BCAA (p less than .001), was unrelated to the dose of non-BCAA, and was inversely related to lactate (p less than .001). These results suggest that BCAA ketoacids contribute to cholesterol synthesis in sepsis, as well as being an oxidative source. The data also suggest that the reduction in alanine in BCAA-enriched amino-acid TPN assists in the lowering of plasma lactate secondary to abnormal septic glucose metabolism. PMID- 2104583 TI - Surfactant therapy for pulmonary edema due to intratracheally injected bile acid. AB - Intratracheally injected bile acid has been shown to produce severe pulmonary edema. We investigated the therapeutic effect of an exogenous surfactant for aspirated bile acid. Anesthetized rabbits were injected intratracheally with 1 ml/kg body weight of taurocholic acid, diluted to 0.6% with normal saline solution. After the injection of taurocholic acid, the PaO2 values decreased, the PaCO2 values increased, and abnormal shadows appeared in chest x-rays. After surfactant injection, the rabbits improved, but pulmonary edema recurred after one hour. After additional injection of the surfactant, the improved condition was sustained for 6 h. All animals in the untreated group died within 5 h and were shown to have severe pulmonary edema. Conversely, microscopic examination revealed no pulmonary edema in animals surviving 6 h after surfactant treatment. Thus, exogenous surfactant can prevent damage to the lung caused by intratracheally injected bile acid. PMID- 2104584 TI - Expression and localization of growth hormone-releasing hormone messenger ribonucleic acid in rat placenta: in vitro secretion and regulation of its peptide product. AB - The placenta is the source of many hypothalamic peptides. We now report that GH releasing hormone (GHRH) mRNA was detectable in rat placenta. On Northern blot hybridization analysis, the size of the placental GHRH transcript was the same with the putative GHRH precursor mRNA. On in situ hybridization, the cells expressing the GHRH mRNA had the morphological characteristics of cytotrophoblasts. In addition, immunoreactive (IR) postranslational products of GHRH were present in rat placental extracts and in the effluent of in vitro perifused placentae. On gel filtration chromatography, the bulk of IR-GHRH present in placental extracts and perifusion effluent had the same size as the authentic hypothalamic GHRH (5.2K). A higher mol wt form of IR-GHRH of about 10K was also present and may represent the pro-GHRH predicted from the sequence of the GHRH cDNA. The mean basal release of IR-GHRH in the perifusion effluent from full thickness rat placental fragments was 337.3 +/- 38.5 (+/- SE; n = 48) pg/10 min fraction.g tissue. Depolarization by 56 mM KCl increased the concentration of the secreted immunoreactive peptide to 632.2 +/- 50.5. A 10-min exposure to 8 bromo-cAMP caused an immediate, monophasic, and dose-dependent increase in IR GHRH secretion, which lasted between 20-30 min. The ensuing response to a KCl pulse was similar in size and pattern to that in the control channels. In contrast, a 10-min pulse of phorbol 12-myristate 13-acetate (a protein kinase-C irreversible activator) induced a gradual, prolonged, and dose-dependent increase in basal GHRH secretion which lasted for at least 4 h. Additionally, phorbol 12 myristate 13-acetate enhanced KCl-induced GHRH secretion. In conclusion, our data suggest that the GHRH gene is expressed in the rat placenta. The placental GHRH transcript and its peptide products appear to have the same size as their hypothalamic counterparts, while the site of its placental GHRH synthesis is the cytotrophoblast. Finally, the secretion of placental GHRH seems to be regulated by both the adenyl cyclase and the protein kinase-C pathways. PMID- 2104585 TI - Corticosteroid regulation of gonadotropin and prolactin secretion in the rat. AB - The purpose of this study was to determine if glucocorticoids had any direct effects on the release of gonadotropin. In estrogen-primed ovariectomized immature rats, triamcinolone acetonide and deoxycorticosterone (1 mg/kg BW) caused a surge in both serum LH and FSH levels. Dexamethasone treatment (0.05 mg/kg BW) resulted in a highly significant selective release of FSH. Cortisol (1 mg/kg BW) suppressed serum FSH levels. A systematic dose-response study showed that triamcinolone acetonide significantly released LH and FSH and suppressed PRL at all doses tested (range, 0.25-4 mg/kg BW). Deoxycorticosterone was not as potent as triamcinolone acetonide and only doses greater than 0.8-1 mg/kg BW significantly released LH and FSH. Dexamethasone selectively released FSH at low doses (0.01, 0.02, 0.05, and 0.1 mg/kg BW) and inhibited LH at higher doses (0.5 and 1.0 mg/kg BW). A single low dose of dexamethasone (0.02 mg/kg BW) was found to significantly release LH. With respect to PRL secretion, a biphasic effect of dexamethasone was observed in that the lowest dose (0.01 mg/kg BW) stimulated PRL release while the highest dose (1.0 mg/kg BW) significantly inhibited PRL release. Triamicolone acetonide and deoxycorticosterone were found to require estrogen priming for their effects on gonadotropin secretion. The findings in this study raise the possibility that the beneficial effects seen with corticosteroids in inducing ovulation in polycystic ovarian syndrome may be due, in part, to their direct effects upon the release of gonadotropins. PMID- 2104586 TI - Tumor necrosis factor and interleukin-1 may regulate renin secretion. AB - Cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) are not only immunoregulatory polypeptides, but may have endocrine functions. We have studied the direct effects of recombinant and purified TNF and IL-1 on renin secretion using both static incubations and perifusions of rat renal cortical slices. Ultrapure human IL-1 (hIL-1) at concentrations as low as 5 U/ml (3 X 10( 12) M) significantly stimulated renin secretion (control, 98 +/- 4%; hIL-1, 153 +/- 13%; P less than 0.01). TNF similarly induced renin release [control, 97 +/- 6%; TNF (10 U/ml), 151 +/- 13%; P less than 0.005]. TNF and recombinant human IL 1 beta (rhIL-i beta) also blocked the inhibitory actions of angiotensin-II (AII) on renin release [control, 100 +/- 3%; AII (2 X 10(-7) M), 80 +/- 5%; AII plus TNF (20 U/ml), 102 +/- 7%; AII plus rhIL beta (10 U/ml), 106 +/- 6%; both P less than 0.02 vs. AII]. A cyclooxygenase (CO) blocker, meclofenamate (M), which does not significantly alter basal renin release, attenuated the TNF- and rhIL-1 beta induced renin secretion [TNF (20 U/ml), 132 +/- 11%; TNF plus M (5 X 10(-5) M), 100 +/- 3% (P less than 0.01); rhIL-1 beta (10 U/ml), 135 +/- 9%; rhIL-1 beta plus M, 105 +/- 10% (P less than 0.05)]. The stimulatory effects of TNF and IL-1 on renin were reversible. These results suggest that IL-1 and TNF are renin secretagogues and can also block the inhibitory actions of AII on renin. Since the effect of TNF and IL-1 on renin can be blocked by a (CO) inhibitor, the studies indicate a role of prostaglandins in their action. Therefore, locally produced TNF and IL-1 may play an important paracrine role in regulation of the renin-angiotensin system. PMID- 2104587 TI - The paraventricular nucleus of the hypothalamus has a major role in thyroid hormone feedback regulation of thyrotropin synthesis and secretion. AB - The role of the hypothalamic paraventricular nucleus (PVN) in thyroid hormone regulation of TSH synthesis during hypothyroidism was studied in adult male rats that were normal (n = 10), had primary hypothyroidism with sham lesions in the hypothalamus (n = 17), and had primary hypothyroidism with PVN lesions (n = 14). Two and 4 weeks after initiation of treatment, plasma levels of thyroid hormones (TSH, corticosterone and PRL) and pituitary content of TSH beta and alpha-subunit mRNA were measured. TRH mRNA levels in the PVN were determined by in situ hybridization histochemistry. At 2 weeks, despite a decrease in plasma free T4 in both hypothyroid groups, plasma TSH levels increased, but to a lesser degree, in the hypothyroid PVN lesioned compared to hypothyroid sham-lesioned group (7.8 +/- 1.3 vs. 20.5 +/- 1.1 ng/dl; P less than 0.05). Similarly, at 4 weeks, the hypothyroid PVN-lesioned group demonstrated a blunted TSH response compared to the hypothyroid sham-lesioned group (6.8 +/- 0.7 vs. 24.0 +/- 1.3 ng/dl; P less than 0.05). Plasma corticosterone and PRL did not significantly differ between sham-lesioned and PVN-lesioned groups. TSH beta mRNA levels markedly increased in hypothyroid sham-lesioned rats compared to those in euthyroid controls at 2 weeks (476 +/- 21% vs. 100 +/- 39%; P less than 0.05) and 4 weeks (1680 +/- 270% vs. 100 +/- 35%; P less than 0.05). In contrast, TSH beta mRNA levels did not increase with hypothyroidism in the PVN-lesioned group compared to those in euthyroid controls at 2 weeks (140 +/- 16%, P = NS) and only partially increased at 4 weeks (507 +/- 135; P less than 0.05). alpha mRNA levels at 4 weeks markedly increased in hypothyroid sham-lesioned rats compared to those in euthyroid controls (1121 +/- 226% vs. 100 +/- 48%; P less than 0.05), but did not increase in the hypothyroid PVN-lesioned rats (61 +/- 15%; P = NS). TRH mRNA in the PVN increased in the hypothyroid sham-lesioned rats compared to those in euthyroid controls (16.6 +/- 1.3 vs. 4.8 +/- 1.2 arbitrary densitometric units; P less than 0.05), and TRH mRNA was not detectable in the PVN of hypothyroid-lesioned rats at 2 weeks. In summary, lesions in rat PVN prevented the full increase in plasma TSH, pituitary TSH beta mRNA, and alpha mRNA levels in response to hypothyroidism. Thus, factors in the PVN are important in thyroid hormone feedback regulation of both TSH synthesis and secretion. PMID- 2104588 TI - Thyrotropin-releasing hormone inhibits GH4 pituitary cell proliferation by blocking entry into S phase. AB - TRH inhibits the proliferation of GH4 rat pituitary cells. We have characterized TRH inhibition of cell proliferation by four approaches: cell number, [3H]thymidine incorporation per culture, bromodeoxyuridine (BrdUrd) incorporation per cell, and cell cycle distribution. TRH decreases GH4 cell number within 18 h of treatment, and this inhibition is maintained for up to 96 h. TRH inhibits [3H]thymidine incorporation into GH4 cell cultures as early as 12 h, and the inhibition of [3H] thymidine incorporation correlates, after a 6-h lag, with decreased GH4 cell number. TRH inhibition of [3H]thymidine incorporation is concentration dependent and saturable, with half-maximal inhibition (IC50) of 2 nM. TRH inhibition of [3H] thymidine incorporation is receptor number dependent up to 160,000 sites/cell, suggesting no spare receptors for TRH on GH4C1 cells. The precise action of TRH on GH4 cell proliferation was examined by flow cytometry of fluorescein isothiocyanate-anti-BrdUrd- and propidium iodide-DNA stained cells. TRH inhibits the number of cells that incorporate BrdUrd and not the amount of BrdUrd incorporated per cell. Dual analysis indicates that the decreased anti-BrdUrd staining is largely restricted to cells in the early S phase. This action of TRH is prolonged (greater than 32 h) and results in a parallel increase in the number of cells in G2-M and G1. These findings indicate that TRH inhibits GH4 cell proliferation at least in part by inhibiting the number of cells entering the S phase. PMID- 2104589 TI - Ontogeny of gonadotropin-releasing hormone-containing neurons in early fetal development of rhesus macaques. AB - We studied the ontogeny of GnRH neurons in fetal rhesus macaques from days 36-135 of gestation. The nasal region, pituitary, and brain were dissected, fixed in 4% paraformaldehyde, sectioned on a cryostat at 10 microns, and mounted on slides. Immunocytochemistry and in situ hybridization were performed for GnRH, pro-GnRH, and pro-GnRH mRNA on nasal and brain tissues. Immunoreactive LH, FSH, and PRL were determined in developing pituitary glands. At 36 days, clusters of GnRH cells were found in the nasal region only. GnRH fibers extended into the brain, and large bundles projected laterally toward the basal hypothalamus. By day 38 GnRH cells were also localized in the olfactory region of the brain. With increasing fetal age a gradual caudal extension of GnRH cells occurred. These cells were first observed in the basal hypothalamus at 47 days. Cells containing PRL and gonadotropins (LH and FSH) were detected in the pituitary at 47 and 50 days, respectively. Low levels of pro-GnRH mRNA were present in the nasal epithelium and septum by day 38 of gestation. The levels of pro-GnRH mRNA in the nasal area and the brain remained low in the day 50 fetus, but were increased significantly by day 135. These data suggest that GnRH neurons in the primate brain originate in the nasal region. Furthermore, GnRH neurons exhibit low levels of synthetic activity at the early fetal stages, but higher synthetic activity close to term. PMID- 2104590 TI - Inhibin concentrations in ovarian and jugular venous plasma and the relationship of inhibin with follicle-stimulating hormone and luteinizing hormone during the ovine estrous cycle. AB - A heterologous RIA for ovine inhibin was developed which was sufficiently sensitive and specific to describe the peripheral concentrations of immunoreactive inhibin (iINH) during the estrous cycle of the ewe and to examine the effects of cautery of ovarian follicles on concentrations of iINH in ovarian and jugular venous plasma. Parallel logit-log dose-response lines were observed among ovine follicular fluid, ewe plasma, and pure native ovine (31 kDa) and bovine (31 kDa) inhibin. iINH could not be detected in ovariectomized ewe plasma, and there was no apparent cross-reactivity with a variety of structurally related and unrelated hormones and peptides, except a monomeric form of the alpha-subunit of INH, iINH in follicular fluid was 10(4)-fold higher than that in ovarian venous plasma, which was 3-fold higher than that in peripheral plasma. Cautery of the follicles resulted in a 35% reduction in iINH and an 81% reduction in estrogen concentrations in the ovarian vein within 10 min. During the estrous cycle, iINH and FSH were inversely related in samples taken over 30 h in the luteal phase (r = -0.69; P less than 0.001) and in the pre- and postovulatory phases (r = -0.45; P less than 0.001). iINH and LH were not related in the luteal phase, but were weakly positively correlated in the follicular phase (r = 0.31; P less than 0.01). iINH and estrogen concentrations in the follicular phase were also weakly correlated (r = 0.30; P less than 0.001). Furthermore, iINH concentrations rose in the follicular phase and decreased within 3-6 h of the preovulatory surges of LH and FSH, reaching a nadir around the time of the second rise in FSH 24-48 h later. It is concluded that 1) large antral follicles are a major source of peripheral iINH during the ovine estrous cycle; 2) iINH levels increase in the follicular phase with the growth of the dominant follicle and may be inhibited by the preovulatory surge of gonadotropin; 3) the fall in inhibin after the LH surge may be responsible for the second rise in FSH; and 4) the inverse relationship between FSH and iINH is consistent with the hypothesis that inhibin is involved in the feedback regulation of FSH. PMID- 2104591 TI - An immunocytochemical and ultrastructural study of adenohypophyses of mice transgenic for human growth hormone. AB - Adenohypophysial morphology in 12 mice transgenic for methallothionein-I-human (h) GH fusion gene was investigated by immunocytochemistry and electron microscopy. The sustained oversecretion of hGH stimulated body growth. The pituitary glands of 6-month-old transgenic mice were significantly decreased in weight and showed marked morphological changes in somatotrophs, lactotrophs, corticotrophs, and gonadotrophs. GH-immunoreactive cells were greatly reduced in size and midly decreased in number; by electron microscopy, the organelles implicated in hormone synthesis were inconspicuous in this cell type. Transgenic males were hypoprolactinemic, presumably due to lactogenic activity of hGH in rodents. Their pituitaries displayed few and slender PRL-immunoreactive cells; ultrastructurally, they belonged to immature (type II) lactotrophs. However, in females, PRL-containing cells showed no change in number, size, or distribution compared to controls. Prior biochemical studies demonstrated high blood levels of LH in males. Their pituitaries contained highly active gonadotrophs resembling gonadectomy cells, consistent with the view that these changes are related to PRL like activity of hGH in mice. In both sexes, stimulated corticotrophs were present. The results indicate that some changes in adenohypophysial cells of mice transgenic for hGH can be attributed to protracted overproduction of the heterologous GH, whereas others can be explained by lactotrophic activity of hGH in mice. The divergent morphological responses of lactotrophs and gonadotrophs in the two sexes may reflect differences in the hormonal regulatory mechanisms between male and female mice. PMID- 2104592 TI - Luteinizing hormone (LH)-releasing hormone: effects on maintenance of immunoreactive follicle-stimulating hormone and LH in adenohypophysial cells. AB - We investigated the importance of LHRH on the maintenance of FSH and LH immunoreactivity in gonadotrophs. Hypophysectomized orchidectomized hamsters (hosts) each received an allograft of a 7-week-old male hamster pituitary gland beneath their right renal capsule. Starting 6 days after transplantation, hosts were injected sc, twice daily with 1 micrograms LHRH or vehicle for 16 days. Twelve hosts in each group were killed by decapitation 16 h after the last injection. Allografts from six of the hamsters in each group and pituitary glands in situ from 10-week-old normal males were prepared for histological examination. Sections of tissue were stained for FSH or LH and with hematoxylin. Allografts from the remaining hamsters were homogenized to measure FSH and LH concentrations. In allografts from the vehicle-treated hosts, 22.8% of adenohypophysial cells stained for LH, while only 16.9% stained for FSH. In allografts from LHRH-treated hosts, 22.6% and 23.8% of the adenohypophyses cells stained for LH and FSH, respectively. Adenohypophyses that developed for the same length of time in situ had 24.8% and 24.1% of the cells staining for LH and FSH, respectively. Matching of some of the FSH and LH cells in serial flip-flopped sections of tissue from all hamsters revealed that many if not all gonadotrophs contained LH. LH- and FSH-containing cells in allografts were similar in size and shape, but were smaller and more circular in profile than those observed in situ. Treatment of hosts with LHRH did not alter gonadotroph size or shape, but it did reduce allograft LH concentration and elevate the serum FSH concentration compared to that in the vehicle-treated hamsters. These results suggest that in the hamster LHRH 1) plays a major role in maintaining FSH immunoreactivity in adenohypophysial tissue, 2) does not play a role in maintaining numbers of immunoreactive LH cells in adult adenohypophysial tissue, and 3) functions to maintain FSH synthesis at least in part in cells that contain LH. PMID- 2104593 TI - Cytotoxic effects of cytokines on islet beta-cells: evidence for involvement of eicosanoids. AB - Arachidonic acid metabolites (eicosanoids) have been implicated in mediating actions of cytokines in different tissues. In this study, we tested inhibitors of arachidonate metabolism for possible protection against the toxic effects of the cytokine combination of tumor necrosis factor (TNF, 100 U/ml) and interferon gamma (IFN-gamma, 100 U/ml) in rat islet cell monolayer cultures, using a 51Cr release cytotoxicity assay to measure islet cell lysis (% 51Cr release). The toxic effect of TNF/IFN-gamma (26.6 +/- 3.7%) was inhibited partially by both a cyclooxygenase inhibitor, indomethacin and a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), and combination of maximally effective concentrations of Indo and NDGA (30 microM) produced further protection against TNF/IFN-gamma-induced lysis (3.5 +/- 0.9%). Also, the combined cyclo/lipoxygenase inhibitors, oxyphenbutazone and eicosa 5,8,11,14 tetrynoic acid, as well as the phospholipase A2 inhibitor, bromophenacyl bromide, significantly inhibited the cytotoxic effect of TNF/IFN-gamma. Whereas indomethacin and NDGA did not prevent TNF/IFN-gamma-induced inhibition of insulin release, this recovered after cytokine removal from cultures protected by the cyclo/lipoxygenase inhibitors. These results suggest that arachidonate metabolites may be involved in mediating the cytotoxic and not the functional inhibitory effects of TNF and IFN-gamma in islet cells. PMID- 2104594 TI - Long-term care benefits for federal employees? PMID- 2104595 TI - Binding of Pseudomonas aeruginosa to neutral glycosphingolipids of rabbit corneal epithelium. AB - 35S-labeled Pseudomonas aeruginosa isolates were shown to bind to neutral glycosphingolipids (NGSLs) of rabbit corneal epithelia in culture by a thin-layer chromatogram overlay procedure. The lipids of the corneal epithelial cells grown in culture were extracted and partitioned into a chloroform-rich lower phase containing NGSLs and an aqueous upper phase containing gangliosides. By using a dot-blot assay, at least six times more radiolabeled P. aeruginosa isolates were shown to bind to the lipids in the lower phase compared with those in the upper phase. Thin-layer chromatography of the lower-phase lipids followed by staining with an orcinol spray revealed at least 10 NGSL components and several fast migrating, nonglycosylated neutral lipid components (including cholesterol). 35S labeled P. aeruginosa was shown to bind to NGSL components 1, 2, 5, 6, and 9. P. aeruginosa-reactive NGSL components 6 and 9 migrated with chromatographic mobilities similar to those of the standards ceramide trihexoside (CT) and ceramide monohexoside, respectively. Components 1 and 2 migrated slightly ahead of asialo GM1, and component 5 migrated faster than globoside but slower than CT. Among the various standards tested, P. aeruginosa bound to asialo GM1 and, to a lesser extent, to ceramide dihexoside and CT but not to GM1, GD1A, GM3, or ceramide monohexoside. It remains to be determined whether any of the five P. aeruginosa-reactive NGSL components of corneal epithelium identified in this study plays a role in the development of corneal infection. However, we have previously shown that component 9, one of the five P. aeruginosa-reactive NGSL components identified in this study, is present in significantly greater amounts in migrating epithelia than it is in nonmigrating epithelia (N. Panjwani, G. Michalopoulos, J. Song, G. Yogeeswaran, and J. Baum, Invest. Ophthalmol. Vis. Sci., in press). This may prove to be of biological significance because it is generally believed that traumatized (migrating) epithelia are more susceptible to infection than normal (nonmigrating) epithelia are. PMID- 2104596 TI - Modulation of sensitivity of blood forms of Trypanosoma cruzi to antibody mediated, complement-dependent lysis. AB - The numerous reports on lysis of blood (trypomastigote) forms of Trypanosoma cruzi by specific antibodies plus complement have systematically shown that a certain proportion of parasites survives. However, it is not known whether the insensitive organisms represent a subpopulation (or clones) or a certain developmental phase of otherwise morphologically identical parasites. In this work, we established that partial lysis was not due to the use of insufficient amounts of lytic reagents. Thus, supernatants of lytic reaction mixtures killed the same proportion of T. cruzi as previously unused reagents. Moreover, in parallel tests in which the trypomastigote concentration was up to four times greater than that used in standard lysis tests, the percentages of lysis were comparable. Incubation periods as long as 4 h did not increase the extent of lysis beyond the value observed after only 1 h, indicating that the routinely used 1-h incubation was appropriate. The extent of lysis was not increased by additional amounts of antibody, complement, or both. Instead, trypomastigotes surviving immune lysis, washed, and incubated with fresh diluent for 45 to 120 min before being used in new lysis tests did manifest additional sensitivity to immune lysis. Three successive infections in mice with parasites which had survived immune lysis led to the production of trypanosomes that displayed the same level of resistance to immune lysis as the original, untreated parasite population. Of interest, the average parasitemias of these groups of mice did not evidence a tendency to increase, as might have occurred if an immune-lysis resistant subpopulation had been selected. Since trypomastigotes exhibiting resistance to immune lysis can eventually become sensitive, resistance to immune lysis does not represent an insensitive parasite subpopulation. This resistance appears to be modulated by the presence of the lytic reagents and might involve expression of as yet unidentified surface components playing a role in complement activation. PMID- 2104597 TI - Isolation of tube precipitin antibody-reactive fractions of Coccidioides immitis. AB - Patients presenting with primary coccidioidal infection have been shown by earlier investigators to produce immunoglobulin M (IgM) precipitin antibodies to lysates of mycelial and spherule phases of Coccidioides immitis. This humoral response has been detected by tube precipitin (TP) and immunodiffusion (ID)-TP assays of patient sera, which are valuable aids in early diagnosis of coccidioidomycosis. Several reports of antigenic fractions which show reactivity with patient TP antibody have been published. However, confusion persists with respect to the nature of the specific serologically reactive macromolecule(s). In this study we isolated two TP antibody-reactive antigens (TP-Ags) from an alkali soluble, water-soluble fraction of the inner conidial wall and a culture filtrate plus toluene lysate of the mycelial phase of C. immitis. The crude antigens were first separated by concanavalin A (ConA) chromatography. The TP-Ags were identified in ID-TP assays as 120- and 110-kilodalton (kDa) fractions which were electroeluted from reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis separations of the ConA-bound conidial wall extract and ConA bound culture filtrate plus lysate preparation, respectively. Following electroelution, the 120-kDa fraction was subjected to gel filtration chromatography which yielded a major 240-kDa and minor 120-kDa component. The apparent dimer may be a product of disulfide bond formation resulting from reassociation of the reduced, monomeric components (120 kDa). The latter was suggested by the presence of cysteine in the isolated fraction. The electroeluted 110-kDa fraction was subjected to ion-exchange chromatography. The DEAE-isolated, TP antibody-reactive fraction was identified as antigen 2 in the coccidioidin anti-coccidioidin reference system. Homogeneity of the TP-Ags was demonstrated in silver-stained sodium dodecyl sulfate-polyacrylamide gels of the respective chromatographically isolated fractions. The two purified TP-Ags showed reactivity in the TP and ID-TP assays and were capable of binding patient IgM but comparatively little IgG antibody, as determined by an enzyme-linked immunosorbent assay. It appears that the diagnostic TP reaction between sera from patients with coccidioidomycosis and the ID reference antigens examined in this study is a composite of IgM binding to both a 120-kDa and a 110-kDa antigen. PMID- 2104598 TI - Composition, serologic reactivity, and immunolocalization of a 120-kilodalton tube precipitin antigen of Coccidioides immitis. AB - Diagnosis of coccidioidomycosis largely depends on serologic tests. In this investigation, the enzyme-linked immunosorbent assay (ELISA) was used to detect patient immunoglobulin M (IgM) precipitin antibody binding to a 120-kilodalton (kDa) fraction previously isolated from an alkali-soluble, water-soluble extract of the arthroconidial wall and mycelial culture filtrate plus toluene lysate of Coccidioides immitis. Results of the serologic response to this tube precipitin antigen (TP-Ag) in the ELISA correlated well with results of immunodiffusion assays of 30 serum samples from patients. Immunoelectron microscopic examinations of arthroconidia and spherules were performed with patient IgM precipitin antibodies isolated from sera eluted over a solid-phase immunosorbent column containing the purified 120-kDa TP-Ag. The antibody probe located the 120-kDa TP Ag on the walls of in vitro-grown arthroconidia and spherules. Pronase digestion and heating (100 degrees C, 5 min) had no apparent effect on the activity of the 120-kDa TP-Ag, while periodate oxidation resulted in total loss of its immunodiffusion-TP activity. Analysis of the carbohydrate composition of the TP Ag revealed xylose, 3-O-methylmannose (3-O-MM), mannose, galactose, and glucose. Competitive inhibition ELISAs were used to demonstrate that 3-O-MM is largely responsible for the reactivity of IgM precipitin antibodies with the 120-kDa TP Ag. Synthetic 3-O-MM may be a useful probe for detection of anti-Coccidioides precipitin antibodies in the ELISA. PMID- 2104599 TI - Comparative protection of mice against virulent and attenuated strains of Brucella abortus by passive transfer of immune T cells or serum. AB - Passively transferred immune serum provided significantly greater protection to BALB/c mice against attenuated Brucella abortus 19 than against virulent strain 2308, whether serum donors had been infected with strain 19 or 2308. In contrast, immune T cells conferred better protection upon recipients challenged with the homologous strain of B. abortus. It is hypothesized that strain 2308, but not strain 19, can survive in macrophages after opsonization and that epitopes which induce protective cell-mediated immunity may differ between strains 19 and 2308. PMID- 2104600 TI - Stimulation of antibacterial macrophage activities by B-cell stimulatory factor 2 (interleukin-6). AB - Mononuclear phagocytes provide the major habitat of intracellular bacteria, including Mycobacterium tuberculosis and Mycobacterium bovis. The capacity of B cell stimulatory factor 2 (interleukin-6 [IL-6]) to activate tuberculostatic functions was investigated by using murine bone marrow-derived macrophages (BMM phi). BMM phi stimulated with recombinant IL-6 and subsequently infected with M. bovis organisms failed to inhibit mycobacterial growth. In contrast, marked tuberculostasis was induced by IL-6 in BMM phi that were already infected with M. bovis, indicating that IL-6 has a macrophage-activating function. PMID- 2104601 TI - Bacterial lipopolysaccharide potentiates gamma interferon-induced cytotoxicity for normal mouse and rat fibroblasts. AB - Gamma interferon (IFN-gamma) can be cytolytic for normal mouse fibroblasts isolated from embryonic or adult tissue (R. Dijkmas, B. Decock, H. Heremans, J. Van Damme, and A. Billiau, Lymphokine Res. 8:25-34, 1989). This cytotoxicity has been shown to be transcription and translation dependent, thereby suggesting involvement of a suicidelike mechanism. The dose of IFN-gamma required for cytotoxicity is higher than that needed for antiviral and macrophage activation but can be reduced 10- to 100-fold by cotreatment of the cells with tumor necrosis factor or interleukin-1 (IL-1) or both, two cytokines that by themselves are not toxic for these cells. Here, we show that bacterial lipopolysaccharide (LPS), which alone has no effect on the viability of mouse fibroblasts, stimulates cell suicide induced by IFN-gamma. The effect was observed in cultures that were virtually free of nonfibroblastoid cells. LPS showed its toxicity enhancing effect only if applied on the cells simultaneously with or immediately after treatment with IFN-gamma. Pretreatment of the cells with LPS was ineffective. Inclusion of antibodies directed against tumor necrosis factor alpha or IL-1 alpha in the culture medium did not block the cytotoxic effect of combined IFN-gamma plus LPS treatment. The time courses of cell toxicity appearance in fibroblasts treated with combined IFN-gamma plus LPS or IFN-gamma plus IL-1 were similar. In addition to LPS, heat-killed gram-negative (Escherichia coli) but also gram-positive (Staphylococcus aureus, Listeria monocytogenes) bacteria were found to enhance IFN-gamma-induced cell death. These findings suggest that IFN-gamma formed in vivo during infectious processes directly aggravates tissue destruction. PMID- 2104602 TI - Sequence analysis and expression of the bacterial dichloromethane dehalogenase structural gene, a member of the glutathione S-transferase supergene family. AB - The nucleotide sequence of a cloned 2.8-kilobase-pair BamHI-PstI fragment containing dcmA, the dichloromethane dehalogenase structural gene from Methylobacterium sp. strain DM4, was determined. An open reading frame with a coding capacity of 287 amino acids (molecular weight, 37,430) was identified as dcmA by its agreement with the N-terminal amino acid sequence, the total amino acid composition, and the subunit size of the purified enzyme. Alignment of the deduced dichloromethane dehalogenase amino acid sequence with amino acid sequences of the functionally related eucaryotic glutathione S-transferases revealed three regions containing highly conserved amino acid residues and indicated that dcmA is a member of the glutathione S-transferase supergene family. The 5' terminus of in vivo dcmA transcripts was determined by nuclease S1 mapping to be 82 base pairs upstream of the GTG initiation codon of dcmA. Despite a putative promoter sequence with high resemblance to the Escherichia coli -10 and -35 consensus sequences, located at an appropriate distance from the transcription start point, dcmA was only marginally expressed in E. coli. The strong induction of dichloromethane dehalogenase in Methylobacterium sp. by dichloromethane was abolished by deleting the 1.3-kilobase-pair upstream region of dcmA. Plasmid constructs devoid of this region directed expression of dichloromethane dehalogenase at a constitutively induced level. PMID- 2104603 TI - Biotransformations of carboxylated aromatic compounds by the acetogen Clostridium thermoaceticum: generation of growth-supportive CO2 equivalents under CO2-limited conditions. AB - Clostridium thermoaceticum ATCC 39073 converted vanillate to catechol. Although carboxylated aromatic compounds which did not contain methoxyl groups were not by themselves growth supportive, protocatechuate and p-hydroxybenzoate (nonmethoxylated aromatic compounds) were converted to catechol and phenol, respectively, during carbon monoxide-dependent growth. Syringate is not subject to decarboxylation by C. thermoaceticum (Z. Wu, S. L. Daniel, and H. L. Drake, J. Bacteriol. 170:5705-5708, 1988), and sustained growth at the expense of syringate derived methoxyl groups was dependent on supplemental CO2. In contrast, vanillate was growth supportive in the absence of supplemental CO2, and 14CO2 was the major 14C-labeled product during [carboxyl-14C]vanillate-dependent growth. Furthermore, the decarboxylation of protocatechuate and p-hydroxybenzoate supported methanol- and 1,2,3-trimethoxybenzene-dependent growth (CO2 is required for growth at the expense of these substrates) when supplemental CO2 was depleted from the growth medium, and the decarboxylation of protocatechuate was concomitant with improved cell yields of methanol cultures. These findings demonstrate that (i) C. thermoaceticum is competent in the decarboxylation of certain aromatic compounds and (ii) under certain conditions, decarboxylation may be integrated to the flow of carbon and energy during acetogenesis. PMID- 2104604 TI - Chorismic acid, a key metabolite in modification of tRNA. AB - Chorismic acid is the common precursor for the biosynthesis of the three aromatic amino acids as well as for four vitamins. Mutants of Escherichia coli defective in any of the genes involved in the synthesis of chorismic acid are also unable to synthesize uridine 5-oxyacetic acid (cmo5U) and its methyl ester (mcmo5U). Both modified nucleosides are normally present in the wobble position of some tRNA species. Mutants defective in any of the specific pathways leading to phenylalanine, tyrosine, tryptophan, folate, enterochelin, ubiquinone, and menaquinone have normal levels of cmo5U and mcmo5U in their tRNA. The presence of shikimic acid in the growth medium restores the ability of an aroD mutant to synthesize cmo5U, while O-succinylbenzoate, which is an early intermediate in the synthesis of menaquinone, does not. Thus, chorismic acid is a key metabolite in the synthesis of these two modified nucleosides in tRNA. The absence of chorismic acid blocks the formation of cmo5U and mcmo5U at the first step, which might be the formation of 5-hydroxyuridine. This results in an unmodified U in the wobble position of tRNA(1Val) and in most of the tRNAs normally containing cmo5U and mcmo5U. Since cmo5U and mcmo5U are synthesized under anaerobic conditions, the formation of these nucleosides does not require molecular oxygen. One of the carbon atoms of the side chain, --O--CH2--COOH, originates from the methyl group of methionine. The other carbon atom does not originate directly from the C-1 pool, from the carboxyl group methionine, or from bicarbonate. This metabolic link between intermediary metabolism and translation also exists for another member of the family Enterobacteriaceae, Salmonella typhimurium, as well as for the distantly related gram-positive organism Bacillus subtilis. PMID- 2104605 TI - Agmenellum quadruplicatum M.AquI, a novel modification methylase. AB - The complete type II modification methylase of Agmenellum quadruplicatum was cloned in Escherichia coli as an R.Sau3A fragment of approximately 4.5 kilobases. The coding sequence was contained in a stretch of 1,156 base pairs which was organized into two parallel, partly overlapping open reading frames of 248 and 139 codons. In vivo complementation experiments showed that the synthesis of both predicted peptides was required for full methylase activity. The amino acid sequences were considerably similar to regions of other deoxycytidylate methylases. PMID- 2104606 TI - Role of threonine residue 154 in ligand recognition of the tar chemoreceptor in Escherichia coli. AB - The Tar chemoreceptor of Escherichia coli mediates attractant responses to aspartate, maltose, and phenol, repellent responses to Ni2+ and Co2+, and thermoresponses. To understand the role of threonine residue 154, which is located in the ligand-binding domain of Tar, we replaced the residue with serine, isoleucine, and proline by site-directed mutagenesis. The replacements caused reductions in aspartate sensing but had only a small effect on maltose sensing and almost no effect on phenol sensing, repellent sensing, and thermosensing. These results indicate that Thr-154 of Tar is rather specifically involved in aspartate sensing. The reductions in the response threshold for aspartate by the replacements with serine, isoleucine, and proline were less than 1, about 2, and more than 5 orders of magnitude, respectively. When the corresponding threonine residue in the Tsr chemoreceptor was replaced with the same amino acids, roughly similar reductions in the response threshold for serine resulted. Thus, these threonine residues seem to have a common role in detecting the aspartate and serine attractant families. A mechanism by which these chemoreceptors detect the amino acid attractants is discussed. PMID- 2104607 TI - Nucleotide sequence and cloning in Bacillus subtilis of the Bacillus stearothermophilus pleiotropic regulatory gene degT. AB - The regulatory gene (degT) from Bacillus stearothermophilus NCA1503 which enhanced production of extracellular alkaline protease (Apr) was cloned in Bacillus subtilis with pTB53 as a vector. When B. subtilis MT-2 (Npr- [deficiency of neutral protease] Apr+) was transformed with the recombinant plasmid, pDT145, the plasmid carrier produced about three times more alkaline protease than did the wild-type strain. In contrast, when B. subtilis DB104 (Npr- Apr-) was used as a host, the transformant with pDT145 could not exhibit any protease activity. After construction of the deletion plasmids, DNA sequencing was done. A large open reading frame was found, and nucleotide sequence analysis showed that the degT gene was composed of 1,116 bases (372 amino acid residues, molecular weight of 41,244). A Shine-Dalgarno sequence was found nine bases upstream from the open reading frame. A B. subtilis strain carrying degT showed the following pleiotropic phenomena: (i) enhancement of production of extracellular enzymes such as alkaline protease and levansucrase, (ii) repression of autolysin activity, (iii) decrease of transformation efficiency for B. subtilis (competent cell procedure), (iv) altered control of sporulation, (v) loss of flagella, and (vi) abnormal cell division. When B. stearothermophilus SIC1 was transformed with the recombinant plasmid carrying degT, the transformants exhibited abnormal cell division. These phenomena are similar to those of the phenotypes of degSU(Hy) (hyperproduction), degQ(Hy), and degR mutants of B. subtilis. However, the amino acid sequence of the degT product (DegT) is different from those of the reported gene products. Furthermore, DegT includes a hydrophobic core region in the N terminal portion (amino acid numbers 50 to 160), a consensus sequence for a DNA binding region (amino acid numbers 160 to 179), and a region homologous to transcription activator proteins (amino acid numbers 351 to 366). We discuss the possibility that the membrane protein DegT functions as a sensor protein and transfers the signal of environmental stimuli to the regulatory region of target genes to activate or repress transcription of the genes. PMID- 2104608 TI - Energy-dependent uptake of 4-chlorobenzoate in the coryneform bacterium NTB-1. AB - The uptake of 4-chlorobenzoate (4-CBA) in intact cells of the coryneform bacterium NTB-1 was investigated. Uptake and metabolism of 4-CBA were observed in cells grown in 4-CBA but not in glucose-grown cells. Under aerobic conditions, uptake of 4-CBA occurred with a high apparent affinity (apparent Kt, 1.7 microM) and a maximal velocity (Vmax) of 5.1 nmol min-1 mg of protein-1. At pH values below 7, the rate of 4-CBA uptake was greatly reduced by nigericin, an ionophore which dissipates the pH gradient across the membrane (delta pH). At higher pH values, inhibition was observed only with valinomycin, an ionophore which collapses the electrical potential across the membrane (delta psi). Under anaerobic conditions, no uptake of 4-CBA was observed unless an alternative electron acceptor was present. With nitrate as the terminal electron acceptor, 4 CBA was rapidly accumulated by the cells to a steady-state level, at which uptake of 4-CBA was balanced by excretion of 4-hydroxybenzoate. The mechanism of energy coupling to 4-CBA transport under anaerobic conditions was further examined by the imposition of an artificial delta psi, delta pH, or both. Uptake of 4-CBA was shown to be coupled to the proton motive force, suggesting a proton symport mechanism. Competition studies with various substrate analogs revealed a very narrow specificity of the 4-CBA uptake system. This is the first report of carrier-mediated transport of halogenated aromatic compounds in bacteria. PMID- 2104609 TI - Conjugal mobilization of streptococcal plasmid pMV158 between strains of Lactococcus lactis subsp. lactis. AB - pMV158, a non-self-transmissible plasmid encoding tetracycline resistance, was conjugally transferred from Enterococcus faecalis JH203 to Lactococcus lactis subsp. lactis IL1403. This transfer appeared to be dependent on the cotransfer of the conjugative plasmids pAM beta 1 or pIP501. Intraspecies conjugal transfer of pMV158 also occurred in strain IL1403. In contrast to the transfer from E. faecalis, transfer in IL1403 did not require the presence of a conjugative plasmid in the donor strain but, rather, appeared to be dependent on putative chromosomal functions in strain IL1403. The transfer of pMV158 from strain IL1403 required the presence of an active pMV158-encoded protein, which showed homology to the Pre (plasmid recombination enzyme) proteins encoded by several small plasmids extracted from Staphylococcus aureus, such as pT181. PMID- 2104610 TI - Intracellular serine protease 1 of Bacillus subtilis is formed in vivo as an unprocessed, active protease in stationary cells. AB - Western immunoblots and assays of Bacillus subtilis extracts showed that intracellular serine protease 1 is produced in a form larger than previously reported, appears not to have undergone N-terminal processing, and is active in the presence or absence of calcium. No evidence for an inactive precursor form of the protease was found. PMID- 2104611 TI - Isolation and characterization of mutations in the gene encoding an endogenous Bacillus subtilis beta-galactosidase and its regulator. AB - We have isolated mutations that appear to inactivate the gene (lacA) encoding an endogenous beta-galactosidase activity in Bacillus subtilis and in a closely linked negative regulatory element (lacR). Both genes map to the hisA-thrA region. The lacA mutations may help to avoid some of the problems arising from the use of the Escherichia coli lacZ gene as a reporter gene in B. subtilis. PMID- 2104612 TI - Evidence that UGA is read as a tryptophan codon rather than as a stop codon by Mycoplasma pneumoniae, Mycoplasma genitalium, and Mycoplasma gallisepticum. AB - Molecular cloning and sequencing showed that Mycoplasma gallisepticum, like Mycoplasma capricolum, contains both tRNA(UCA) and tRNA(CCA) genes, while Mycoplasma pneumoniae and Mycoplasma genitalium each appear to have only a tRNA(UCA) gene. Therefore, these mycoplasma species contain a tRNA with the anticodon UCA that can translate both UGA and UGG codons. PMID- 2104613 TI - Dramatic increase in negative superhelicity of plasmid DNA in the forespore compartment of sporulating cells of Bacillus subtilis. AB - Plasmid pUB110, isolated from vegetative cells of Bacillus subtilis, has an average of 34 negative supertwists (tau av = -34). This value falls to -30 early in sporulation, and the plasmid in the mother cell compartment maintains a tau av of -30. However, the plasmid within the developing forespore becomes much more negatively supercoiled, reaching a tau av of -47 in the dormant spore. This increased negative supercoiling in the forespore plasmid takes place in parallel with the synthesis of small, acid-soluble spore proteins, alpha and beta; and the plasmid from spores lacking small, acid-soluble proteins alpha and beta has a tau av of -40. The large increase in negative supercoiling of spore plasmid was also observed with Bacillus megaterium and in B. subtilis containing a plasmid with an origin different from that of pUB110. During spore germination plasmid pUB110 rapidly relaxed back to the tau av value characteristic of vegetative cells. It is possible that the observed changes in forespore plasmid topology are involved in modulating gene expression, DNA photochemistry, or both of these parameters in this compartment. PMID- 2104614 TI - Cloning and DNA sequence of the gene coding for the major sigma factor from Myxococcus xanthus. AB - The gene for a sigma factor (rpoD) was cloned from Myxococcus xanthus, a soil bacterium which differentiates to form fruiting bodies upon starvation for nutrients. The DNA sequence of the gene was determined, and an open reading frame encoding a polypeptide of 708 amino acid residues (Mr = 80,391) was identified. Except for the amino-terminal sequence consisting of 100 residues, the M. xanthus sigma factor (sigma-80) showed extensive similarity with Escherichia coli sigma 70 as well as Bacillus subtilis sigma-43. In particular, the carboxy-terminal sequence of 242 residues that is known to be required for promoter recognition and core recognition showed 78 and 72% amino acid sequence identity with the E. coli and B. subtilis sigma factors, respectively. The putative RpoD protein was detected at the position of an apparent molecular weight of 86,000 by Western blot (immunoblot) analysis by using antiserum against B. subtilis sigma-43, which agreed well with the position of a vegetative sigma factor of M. xanthus previously identified by Rudd and Zusman (K. Rudd and D. R. Zusman, J. Bacteriol. 151:89-105, 1982). PMID- 2104616 TI - Signaling through phosphatidylcholine breakdown. AB - Several mechanisms of agonist control of PC hydrolysis have been described: control by G proteins, protein kinase C, Ca2+, and tyrosine kinases. The relative importance of these mechanisms remains to be demonstrated. Another major point is the physiological significance of PC hydrolysis. The prolonged formation of DAG from PC may be important in cellular control mechanisms that require long term activation of protein kinase C. The functions of PA are presently unknown, but the rapid formation of high concentrations of this lipid during stimulation by agonists strongly suggests that it has signaling functions. It is obvious that much work remains to define the physiological significance of agonist-stimulated PC breakdown. PMID- 2104615 TI - The spoIIJ gene, which regulates early developmental steps in Bacillus subtilis, belongs to a class of environmentally responsive genes. AB - The Bacillus subtilis spoIIJ locus is defined by a Tn917 insertion which leads to an oligosporogenous phenotype. Here we show that this mutation severely decreases transcription of spoIIA, spoIIE, and spoIIG, three operons involved in asymmetric septation, the earliest morphological event of sporulation. A 14.3-kilobase region overlapping the site of the spoIIJ::Tn917 insertion was cloned and the exact location of the spoIIJ gene was defined with various integrative plasmids carrying subfragments of that region. DNA sequencing established that spoIIJ is a monocistronic locus encoding a 606-amino-acid polypeptide which contains a canonical "transmitter" domain, indicating that spoIIJ is a new member of the "sensor" class of signal-transducing systems in bacteria. Thus, spoIIj, which is transcribed during vegetative growth, presumably under the control of sigma H, encodes a protein that could interact with major regulators of early sporulation stages, such as SpoOA and/or SpoOF. PMID- 2104617 TI - Active site structure and antigen binding properties of idiotypically cross reactive anti-fluorescein monoclonal antibodies. AB - This report includes complete VH and V kappa nucleotide and deduced amino acid sequences of idiotypically cross-reactive monoclonal anti-fluorescein antibodies that differed greater than 10(5)-fold in affinity. High affinity monoclonal antibody 4-4-20 and intermediate affinity antibodies 10-25, 5-14, 9-40, 12-40, and 3-24 utilized greater than or equal to 90% homologous VHIIIC germ-line genes. Extensive D segment length and sequence variability were observed; however, compensatory germ-line JH4 (4-4-20 and 3-24) or JH3 (10-25, 5-14, 9-40, and 12 40) sequence lengths resulted in H chain CDR3 + FR4 to be a constant 18 amino acids. In addition, each antibody and low affinity 3-13 rearranged greater than or equal to 96% homologous V kappa II genes to J kappa 1, except for 10-25 (J kappa 5) and 3-13 (J kappa 4). Resolved crystal structure of complexed fluorescein and 4-4-20 Fab fragments revealed residues HisL27d, TyrL32, ArgL34, SerL91, TrpL96, and TrpH33 acted as hapten contact residues. Antibodies 5-14, 9 40, 12-40, and 3-24 primary structures possessed identical contact residues as 4 4-20 except for the substitution of HisL34 for ArgL34. Thus, ArgL34 was implicated in the increased affinity of monoclonal antibody 4-4-20. Finally, it was difficult to correlate extensive H chain CDR3 residue heterogeneity directly with fluorescein binding and idiotypy. PMID- 2104618 TI - Identification of a site in the alpha chain of platelet glycoprotein Ib that participates in von Willebrand factor binding. AB - The binding of von Willebrand factor (vWF) to the platelet receptor glycoprotein (GP) Ib-IX complex is a key event in hemostasis and may participate in the development of thrombotic vascular occlusion. We present here evidence that residues Ser251-Tyr279 in the GP Ib alpha-chain participate in this function. Initial studies suggested that the modality of vWF interaction with GP Ib depended on the conditions used for induction of binding, either in the presence of ristocetin, or botrocetin, or with asialo-vWF. In fact, only the 45-kDa amino terminal fragment of GP Ib alpha inhibited the vWF-GP Ib interaction under all conditions tested, while the 84-kDa macroglycopeptide was significantly effective only in the presence of ristocetin. Moreover, the 45-kDa fragment with reduced disulfide bonds still inhibited ristocetin-induced binding but had no effect, at the concentrations tested, on botrocetin-mediated or direct asialo-vWF binding. In order to localize in more detail the functional site, the entire sequence of the 45-kDa fragment was reproduced in 27 overlapping synthetic peptides that were then used in inhibition of binding assays. This led to the identification of a linear GP Ib alpha sequence (residues Ser251-Tyr279) that effectively inhibited platelet interaction with vWF mediated by ristocetin and, at higher concentration, also by botrocetin. A shorter peptide overlapping with the longer one (residues Gly271-Glu285) was the second most active inhibitory species. This region of the molecule contains several residues with a high surface probability index, as expected for a site involved in ligand binding. Thus, while native conformation of GP Ib alpha appears to be important for optimal interaction with vWF, the results obtained with short synthetic peptides may help in defining the amino acid residues participating in this essential function. PMID- 2104619 TI - Intramitochondrial transfer of phospholipids in the yeast, Saccharomyces cerevisiae. AB - Translocation of phosphatidylinositol, which is synthesized on the outer aspect of the outer membrane of isolated yeast mitochondria, to the inner membrane is linked to phosphatidylinositol synthesis and is therefore a vectorial process. Phosphatidylinositol once integrated into the inner mitochondrial membrane is not transferred back to the mitochondrial surface. Phosphatidylserine is also translocated from the outer to the inner mitochondrial membrane, where it is decarboxylated to phosphatidylethanolamine. We made use of this metabolic modification to characterize the intramitochondrial transfer of phosphatidylserine and phosphatidylethanolamine. Intramitochondrial phosphatidylserine transfer is insensitive to the uncoupler carbonyl cyanide m chlorophenylhydrazone and to valinomycin and is thus independent of an electrochemical gradient across the inner membrane. Transfer of phosphatidylserine from the outer to the inner mitochondrial membrane occurs not only in intact mitochondria but also in mitoplasts which are devoid of intermembrane space proteins but have the outer membrane still adherent to the inner membrane. This result suggests that specific contact sites are involved in the intramitochondrial translocation of phospholipids. 3H-Labeled phosphatidylethanolamine synthesized from [3H]serine in isolated mitochondria is readily exported from the inner to the outer mitochondrial membrane without prior mixing with the pool of phosphatidylethanolamine of the inner membrane. PMID- 2104620 TI - Site-directed mutagenesis of arginine 103 and lysine 185 in the proposed glycosaminoglycan-binding site of heparin cofactor II. AB - Inhibition of thrombin by heparin cofactor (HCII) is accelerated approximately 1000-fold by heparin or dermatan sulfate. We found recently that the mutation Arg189----His decreases the affinity of HCII for dermatan sulfate but not for heparin (Blinder, M. A., Andersson, T. R., Abildgaard, U., and Tollefsen, D. M. (1989) J. Biol. Chem. 264, 5128-5133). Other investigators have implicated Arg47 and Lys125 of anti-thrombin (homologous to Arg103 and Lys185 of HCII) in heparin binding. To investigate the corresponding residues in HCII, we have constructed amino acid substitutions (Arg103----Leu, Gln, or Trp; Lys185----Met, Asn, or Thr) by oligonucleotide-directed mutagenesis of the cDNA and expressed the products in Escherichia coli. The recombinant HCII variants were assayed for binding to heparin-Sepharose and for inhibition of thrombin in the presence of various concentrations of heparin or dermatan sulfate. All of the Arg103 variants bound to heparin with normal affinity. Furthermore, inhibition of thrombin by the Arg103----Leu variant occurred at a normal rate in the absence of a glycosaminoglycan and was accelerated by normal concentrations of heparin and dermatan sulfate. These results indicate that HCII, unlike anti-thrombin, does not require a positive charge at this position for the interaction with heparin or dermatan sulfate. The Arg103----Gln and Arg103----Trp variants inhibited thrombin at about one-third of the normal rate in the absence of a glycosaminoglycan, suggesting that these mutations exert an effect on the reactive site (Leu444-Ser445) of HCII. All of the Lys185 variants bound to heparin with decreased affinity but inhibited thrombin at approximately the normal rate in the absence of a glycosaminoglycan. These variants required greater than 10-fold higher concentrations of heparin to accelerate inhibition of thrombin and were not stimulated significantly by dermatan sulfate, suggesting that heparin and dermatan sulfate interact with Lys185 of HCII. These results provide evidence that the glycosaminoglycan-binding site in HCII includes Lys185 but not Arg103, both of which were predicted to be involved by homology to anti thrombin. PMID- 2104621 TI - Interdomain hydrolysis of a truncated Pseudomonas exotoxin by the human immunodeficiency virus-1 protease. AB - The specificity of HIV-1 (human immunodeficiency virus-1) protease has been evaluated relative to its ability to cleave the three-domain Pseudomonas exotoxin (PE66) and related proteins in which the first domain has been deleted or replaced by a segment of CD4. Native PE66 is not hydrolyzed by the HIV-1 protease. However, removal of its first domain produces a molecule which is an excellent substrate for the enzyme. The major site of cleavage in this truncated exotoxin, called LysPE40, occurs in a segment that connects its two major domains, the translocation domain (II), and the ADP-ribosyltransferase (III). This interdomain region contains the sequence ...Asn-Tyr-Pro-Thr... which is similar to that surrounding the scissile Tyr-Pro bond in the gag precursor polyprotein, a natural substrate of the HIV-1 protease. Nevertheless, it is not this sequence that is recognized and cleaved by the enzyme, but one 6 residues away, ...Ala-Leu-Leu-Glu... in which the Leu-Leu peptide bond is hydrolyzed. A second, slower cleavage takes place at the Leu-Ala bond 3 residues in from the NH2 terminus of LysPE40. When domain I of PE66 is replaced by a segment comprising the first two domains of CD4, the resulting chimeric protein is hydrolyzed at the same Leu-Leu bond by HIV-1 protease. Enzyme activities toward synthetic peptides modeled after the sequences defined above in LysPE40 are in complete accord, relative to specificity, kinetics, and pH optimum, with results obtained in the hydrolysis of the parent protein. These findings demonstrate that ideas concerning the specificity of the HIV-1 protease that are based solely upon its processing of natural viral polyproteins can be expanded by evaluation of other multidomain proteins as substrates. Moreover, it would appear that it is not a particular conformation, but sequence and accessibility that play the dominant role in defining sites in a protein substrate that are susceptible to hydrolysis by the enzyme. PMID- 2104622 TI - Isolation of Chinese hamster ovary ribosomal mutants differentially resistant to ricin, abrin, and modeccin. AB - The molecular action of ricin A chain involves cleavage of the N-glycosidic bond between ribose and the adenine 4324 nucleotides from the 5' end of mammalian 28 S rRNA (Endo, Y., and Tsurugi, K. (1987) J. Biol. Chem. 262, 8128-8130). In this paper, four ricin- and abrin-resistant Chinese hamster ovary cell mutants that possess ribosomes resistant to this N-glycosidase action are described. Three of the mutant phenotypes, Lec26, Lec27, and Lec28, were recessive in somatic cell hybrids and define at least two new lectin-resistant complementation groups. The most extensively characterized mutant type, LEC17, was dominant in such hybrids. None of the mutants were cross-resistant to modeccin. Post-mitochondrial supernatants from each of the four mutants were resistant to inhibition of cell free protein synthesis by ricin, ricin A chain, and abrin. In addition, polysomes isolated from mutant cells were resistant to cleavage of the adenine-ribose N glycosidic bond by ricin A chain or abrin, as assayed by the release of an approximately 470-nucleotide fragment following aniline treatment of ribosomal RNA extracted from toxin-treated polysomes. The unique lectin-resistance properties of the different mutants suggests that the accessibility of adenine 4324 to each toxin differs. It seems likely that the recessive Chinese hamster ovary ribosomal mutants reflect structural changes in different ribosomal proteins while the dominant phenotype may be due to the modification of protein(s) or rRNA involved in toxin-ribosome interaction. Further analysis of these cell lines should provide new insights into the structure/function relationships of eukaryotic ribosomes. PMID- 2104623 TI - Gonadal control of pulsatile secretion of luteinizing hormone and follicle stimulating hormone in prepubertal boys evaluated by ultrasensitive time-resolved immunofluorometric assays. AB - To elucidate the role of the testis in the control of LH and FSH secretion before puberty, we examined pulsatile LH and FSH secretion in six prepubertal boys with primary testicular failure (two boys with masculine pseudohermaphroditism, two boys with the Klinefelter's syndrome, and two boys with anorchia) and eight normal prepubertal boys. Plasma LH and FSH levels were measured every 15 min for 6 h during the day and night with ultrasensitive (0.019 and 0.014 IU/L) time resolved immunofluorometric assays. In all six hypogonadal boys the mean FSH level was above the range of the normal prepubertal boys, whereas the LH level was elevated in only one boy. All boys had LH and FSH pulses. The FSH pulse interval in the anorchid boys was shorter than that in the normal boys, but this was not observed in the other hypogonadal boys. The LH pulse interval in the anorchid and other hypogonadal boys was the same as that in the normal boys. The FSH pulse amplitudes were higher in the anorchid and other hypogonadal boys than in the normal boys, but the LH pulse amplitudes were higher only in the anorchid boys. We conclude that in prepuberty the testes have little effect on LH secretion, but that they are involved in the regulation of FSH levels. In primary testicular failure, the elevation of FSH levels is associated with an increase in FSH pulse amplitude and, in the absence of testicular steroids, possibly also with an increase in FSH pulse frequency. PMID- 2104624 TI - Acute administration of corticoids: a new and peculiar stimulus of growth hormone secretion in man. AB - It is widely accepted that chronic administration of corticoids in man inhibits the GH response to all of the stimuli tested so far. To study the action of corticoids administered acutely, several dexamethasone challenge tests were performed, after which GH levels were measured for 7 h. In eight volunteers, administration of 4 mg dexamethasone (Dex), iv, induced a clear-cut GH release compared with saline administration. The secretion followed an unusual pattern; basal GH levels (1.5 +/- 0.1 micrograms/L) started rising 2 h after Dex injection, reaching a peak of 17.5 +/- 4.4 micrograms/L after 3 or 3.5 h. Peak levels were maintained until 5 h post-Dex and decreased thereafter. Similar data were obtained when Dex was administered to five volunteers at the dose of 8 mg, orally, with a 30-min delay of the GH peak (19.6 +/- 7.9 micrograms/L). To study whether there was a cholinergic input responsible for the Dex action, another group of eight volunteers underwent three Dex tests (4 mg, iv) on three occasions, followed 90 min later by the administration of placebo (control), atropine (0.5 mg, iv), or pyridostigmine (120 mg, orally). The Dex-induced GH peak (20.8 +/- 5.2 micrograms/L) was not significantly increased by pyridostigmine (cholinergic agonist) treatment (24.2 +/- 4.0 micrograms/L). The blockade of muscarinic receptors by atropine induced a delay in the Dex-induced secretory peak, which appeared at 5 h. However, the Dex-atropine GH peak (14.9 +/ 4.1 micrograms/L) was not different from the Dex-placebo one. In conclusion, Dex alone is able to induce a clear-cut GH secretion in man. The stimulus followed a peculiar time pattern, with peaks levels attained 3 h after either iv or oral administration. PMID- 2104625 TI - Change in electrophoretic mobility of human follicle-stimulating hormone in serum after administration of gonadotropin-releasing hormone. AB - The median electrophoretic mobility of FSH in serum (S-FSH) was determined in 14 girls, aged 9-14 yr, with Turner's syndrome before and after iv administration of GnRH. The basal S-FSH level varied almost 100-fold between patients. Less negatively charged forms of FSH appeared in serum in all patients after GnRH stimulation. The aim of the study was to determine if the change in electrophoretic mobility of S-FSH after GnRH treatment was related to the basal S FSH level, the absolute or relative increase in the S-FSH level after GnRH, or the electrophoretic mobility of S-FSH present in the basal state. A highly significant (r = 0.94; P less than 0.001) correlation was found between the relative increase in S-FSH 60 min after GnRH treatment and the decrease in electrophoretic mobility. A selective survival of different forms of FSH in the circulation is proposed as the most likely explanation for the appearance in serum of the less negatively charged forms of FSH after GnRH stimulation. PMID- 2104626 TI - Effects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose-dependent suppression of luteinizing hormone, follicle-stimulating hormone, and sperm production. AB - In normal men, chronic testosterone (T) administration results in negative feedback suppression of gonadotropin and sperm production. However, azoospermia is achieved in only 50-70% of men treated with high dosages of T. Furthermore, the relative sensitivity of LH and FSH secretion to chronic administration of more physiological dosages of T is unclear. We determined whether a T dosage higher than those previously given would be more or less effective in suppressing spermatogenesis and whether, within the physiological range, T would exert a more selective effect on LH than on FSH secretion. After a 4- to 6-month control period, 51 normal men were randomly assigned to treatment groups (n = 9-12/group) receiving either sesame oil (1 mL) or T enanthate (25, 50, 100, or 300 mg, im) weekly for 6 months. Monthly LH and FSH levels by RIA and twice monthly sperm counts were determined. During treatment, T levels were measured daily between two weekly injections. Chronic T administration in physiological to moderately supraphysiological dosages resulted in parallel dose-dependent suppression of LH, FSH, and sperm production. T enanthate (50 mg/week) suppressed LH and FSH levels and sperm counts to 50% of those in placebo-treated men (ED50). T enanthate (300 mg/week), was no more effective than 100 mg/week in suppressing LH, FSH, and sperm production. Serum T levels in men who received 100 and 300 mg/week T enanthate were 1.5- and 3-fold higher than those in placebo-treated men, respectively. Except for mild truncal acne, weight gain, and increases in hematocrit, we detected no significant adverse health effects of chronic high dosage T administration. We conclude that 1) LH and FSH secretion are equally sensitive to the long term negative feedback effects of T administration; 2) sperm production is suppressed in parallel with the LH and FSH reductions induced by chronic T administration; and 3) even at the clearly supraphysiological dosage of 300 mg/week, T enanthate does not reliably induce azoospermia in normal men. However, there was also no evidence of a stimulatory effect of this T dosage on spermatogenesis. Furthermore, we found no evidence of major adverse health effects of T administered chronically even at the highest dosage. PMID- 2104627 TI - Effect of the circulating renin-angiotensin system on prolactin release in humans. AB - We recently reported that renin, angiotensinogen, and angiotensin-converting enzyme were present in normal human pituitary lactotroph cells and PRL-secreting adenomas. Angiotensin-II and -III have also been shown to modulate PRL release in vitro. The present study was designed to determine whether angiotensin modulates PRL secretion in vivo. In 36 hypertensive patients with widely varying renin levels, active renin and basal PRL levels did not correlate. In 10 normal volunteers, both a sustained infusion of angiotensin-II and a graded infusion of angiotensin-III induced a 2- to 3-fold increase in aldosterone levels, but had no effect on PRL secretion. Administration of the angiotensin-converting enzyme inhibitor captopril had no effect on PRL circadian rhythm in 10 normal subjects or on PRL concentrations in 11 patients with PRL-secreting adenomas. Cross-over administration of placebo and captopril did not affect the peak PRL level measured after TRH treatment in 10 hypertensive men (placebo, 43.1 +/- 5.4; captopril, 40.0 +/- 6.2 micrograms/L; P = NS) or the rise in PRL induced by doperidone in 6 normal women (placebo, 129.5 +/- 16.2; captopril, 150.0 +/- 35.7 micrograms/L; P = NS). Further, administration of enalapril for 30 days to 6 hypertensive patients did not alter basal PRL concentrations or the peak concentrations induced by TRH. These data indicate that in humans the circulating renin-angiotensin system does not interact with diurnal PRL release or with the response to TRH or domperidone. PMID- 2104628 TI - Decreased nocturnal surge of thyrotropin in nonthyroidal illness. AB - To evaluate the regulation of TSH secretion in nonthyroidal illness (NTI) we studied the nocturnal TSH surge in 11 healthy controls and 26 NTI patients; none of the patients was on medication known to interfere with TSH secretion. The presence of a nocturnal TSH surge was defined as a mean nighttime TSH (the mean of 5 samples taken hourly from 0000-0400 h) significantly greater than the mean daytime TSH (the mean of 5 samples taken from 1500-1900 h). A nocturnal TSH surge was present in 11 of 26 NTI patients and in 11 of 11 controls (P less than 0.01). Both the absolute (0.3 +/- 0.1 vs. 1.0 +/- 0.2 mU/L; P less than 0.01) and relative (11 +/- 6% vs. 71 +/- 12%; P less than 0.001) nocturnal TSH surges were lower in NTI patients than in controls. NTI patients had lower plasma T3 (1.11 +/ 0.08 vs. 1.84 +/- 0.11 nmol/L; P less than 0.001) and higher plasma rT3 (0.81 +/ 0.24 vs. 0.23 +/- 0.01 nmol/L; P less than 0.001) concentrations than controls, but T4, FT4, and TSH values were similar in both groups. No differences were found between the 15 NTI patients without nocturnal TSH surge and the 11 patients with a nocturnal TSH surge in sex distribution, age, caloric intake, or plasma T4 and T3, but hospital mortality was slightly, although not significantly, higher in those with an absent nocturnal TSH surge. An absent nocturnal TSH surge occurred in 2 of 2 patients with a low TSH (less than 0.4 mU/L), in 11 of 20 patients with a normal TSH (0.4-4.0 mU/L), and in 2 of 4 patients with a high TSH (greater than 4.0 mU/L). Pituitary TSH responsiveness to TRH was similar in patients with or without a nocturnal TSH surge. We conclude that NTI is frequently associated with a decreased nocturnal TSH surge. This phenomenon is not related to ambient plasma T4, T3, or TSH concentrations or pituitary TSH responsiveness to TRH. A decreased nocturnal TSH surge appears to be one of the features of the sick euthyroid syndrome and is probably related to hypothalamic dysregulation. PMID- 2104629 TI - Atenolol enhances nocturnal growth hormone (GH) release in GH-deficient children during long term GH-releasing hormone therapy. AB - The effect of the selective beta 1-adrenergic blocking agent atenolol (50 or 100 mg, orally) on spontaneous and GH-releasing hormone (GHRH)-stimulated GH release was evaluated in six GH-deficient children during long term therapy with GHRH. Nocturnal GH concentrations were determined every 20 min for 12 h under the following four conditions: 1) control, 2) atenolol administration only, 3) sc GHRH administration only, and 4) combined GHRH and atenolol administration. The mean 12-h nocturnal GH concentrations after administration of atenolol alone [2.4 +/- 0.6 microgram/L (mean +/- SEM)] or GHRH alone (2.7 +/- 1.0 micrograms/L) were indistinguishable from baseline values (2.0 +/- 0.5 microgram/L; P greater than 0.05). In contrast, the addition of atenolol to ongoing GHRH therapy caused a clear augmentation of 12-h overnight GH release compared to that during all other study periods (5.0 +/- 1.3 micrograms/L; P less than 0.05). In a subset of three subjects for whom GH pulse characteristics were determined, the primary mode of the enhanced GH release was through an increase in the amplitude of serum GH pulses. These results are consistent with the hypothesis that beta-adrenergic blocking compounds enhance the responsivity of the pituitary gland to agents that permit GH release by inhibiting hypothalamic somatostatin secretion or action. They suggest that atenolol may have potential as an adjunctive therapy in some children with abnormalities of GH secretion when GHRH is the primary therapeutic agent. PMID- 2104630 TI - Presence of growth hormone-releasing hormone-like immunoreactivity in human tumors: characterization of immunological and biological properties. AB - The distribution and physical and biological properties of GH-releasing hormone like immunoreactivity (GHRH-IR) in human tissues and tumors was investigated using a specific GHRH RIA, gel chromatography, immunoaffinity chromatography, and bioassay with cultured rat anterior pituitary cells. Variable concentrations of GHRH-IR, ranging from 1.4-39.0 ng/g wet wt, were found in normal liver, lung, placenta, and pancreas. In the latter tissue, however, a different chromatographic profile and a marked decrease in GHRH-IR after immunoaffinity occurred, suggesting that GHRH-IR in pancreatic extracts is not native GHRH. In all tumors examined (n = 35) GHRH-IR could be detected, and four tumors (three carcinoids and one jejunal carcinoma) contained a very high amount of GHRH-IR (greater than 1000 ng/g wet wt). Affinity chromatography of tumor extracts led to a significant loss (greater than 50%) of GHRH-IR in nine tumors. The four tumors containing large amounts of GHRH-IR were obtained from two patients with active acromegaly and two patients who had no clinical evidence of acromegaly. Using antibodies with different specificities for GHRH-(1-44) and GHRH shortened at the C-terminus, varying concentrations of GHRH-(1-44) in these tumors were found, ranging from 10-87% of the total GHRH-IR. The biological activity of GHRH in the four tumor extracts was similar to that of synthetic GHRH alone or GHRH added to control tissue subjected to extraction. These results demonstrate the presence of GHRH-IR in the majority of normal tissues and tumors, which, though they may produce large amounts of biologically active GHRH, do not always lead to acromegaly. PMID- 2104631 TI - Ovarian antibodies detected by immobilized antigen immunoassay in patients with premature ovarian failure. AB - An enzyme-linked immunosorbent assay (ELISA) was used to detect ovarian and oocyte antibodies in serum from 45 patients with premature ovarian failure (POF). Control sera were obtained from a similar group of normally cycling women without POF. A specific antibody reaction was found when POF sera were tested against human ovary (47%) or oocytes (47%). A combined total of 69% of the sera were positive for either ovary or oocytes. Fewer sera were positive for antibodies against human thyroid (18%) or human placenta (22%), and virtually no reaction with human liver (4%) was seen. LH antibodies were detected by ELISA against LH in only 3 POF sera that also contained ovarian antibodies. Therefore, gonadotropin antibodies alone do not appear to account for POF. In addition, 2 patients were treated by immunosuppression and became pregnant coincident with a decline in the serum concentration of ovarian antibodies. In summary, the results of this study are consistent with previous immunohistochemical data which indicate that ovarian and oocyte antibodies are common in patients with POF. This supports the concept that some forms of POF are associated with an autoimmune process. Furthermore, detection of ovarian and oocyte antibodies by ELISA may permit routine diagnosis of autoimmune POF and provide a basis for therapy. PMID- 2104632 TI - A quantitative cytochemical method for ornithine decarboxylase activity. AB - Although decarboxylases, particularly ornithine decarboxylase, are of considerable importance in cell metabolism, it has been impossible to demonstrate their activity histochemically, as this depends on trapping carbon dioxide at neutral pH values. A new reagent, lead hydroxyisobutyrate, has been shown capable of such trapping. It has been applied to the demonstration of ornithine decarboxylase activity in mouse kidney. Optimal concentrations of substrate, co factor and trapping agent, as well as the pH optimum, have been determined for cryostat sections stabilized with a collagen polypeptide. The activity was inhibited by the specific ornithine decarboxylase inhibitor alpha-difluoromethyl ornithine. PMID- 2104633 TI - Light microscopic localization of glycosyltransferase activities in cells and tissues. AB - We describe an assay for light microscopic visualization of specific glycosyltransferases on tissue sections or on cells. The assay uses a sequence of enzyme reactions that yields two moles of NADH for each mole of the uridine-5' diphosphate (UDP) released during transfer of a monosaccharide from a UDP sugar to an acceptor. When diaphorase and tetrazolium salts are present in the incubation mixture, the tetrazolium salts are reduced to colored diformazans, which precipitate at the sites of glycosyltransferase activity. The validity of the assay was established by applying the technique to spermatozoa and liver, in which some glycosyltransferases have previously been localized. When suspensions of mouse spermatozoa were assayed for galactosyltransferase (GalTase) activity, diformazan precipitates appeared on the plasma membranes overlying the anterior heads of the spermatozoa, in agreement with immunochemical localizations. In mouse liver slices assayed with bilirubin as acceptor for glucuronyltransferase (GluTase) activity, dense diformazan deposits appeared on the hepatocytes but not on endothelial cells, also in agreement with immunochemical data. In the absence of acceptor or UDP sugar donor, diformazan deposits were minimal and random in all tissues tested. The assay's versatility was tested by incubating tissues with different sugar donors and acceptors to localize other sites of transferase activity. In mouse frozen liver sections, GalTase activity occurred in both hepatocytes and endothelial cells; in sections of rat submaxillary glands, GalTase activity was detected in mast cells. In liver sections, GlcuTase activity with o-aminophenol as acceptor was located primarily on the endothelial cells. With the appropriate sugar donor and acceptor, this assay should detect any transferase, other than the glucosyltransferases, that utilizes UDP sugars. PMID- 2104634 TI - Caring versus noncaring staff behaviors--their impact on the elderly. PMID- 2104635 TI - Re: Effects of prostaglandin E1 on penile erection and erectile failure. PMID- 2104636 TI - Adherence of uropathogenic E. coli to differentiated human uroepithelial cells grown in vitro. AB - A quantitative in vitro model to measure E. coli adherence to differentiated human uroepithelial cells has been developed. Primary cultures of uroepithelial cells were initiated from normal ureteral epithelium. Adherence of uropathogenic 3H-labelled Escherichia coli to postconfluent human uroepithelial cells was directly related to the bacteria:epithelial cell ratio during incubation. Bacterial attachment was inhibited either by mannose or by urine containing anti E. coli antibodies. Transmission electron microscopy showed that epithelial cells differentiated in vitro to resemble normal uroepithelium in vivo. Furthermore, electron microscopy showed specific adherence of bacteria to the glycocalyx of microvilli of the superficial uroepithelial cells in vitro in a manner which closely mimics the in vivo interaction. This model of bacterial adherence permits in vitro analysis of adhesin-receptor interactions between uropathogenic E. coli and a layer of viable uroepithelial cells similar to those lining the bladder. PMID- 2104637 TI - Topical mitomycin C therapy for carcinoma in situ of the bladder: a followup. AB - We studied 15 patients with histologically proved multifocal carcinoma in situ of the bladder who were in remission at a mean followup of 21 months after induction intravesical chemotherapy with mitomycin C. These patients have been followed for a further 28 months, for a total mean duration of 49 months. Of the 15 patients 4 suffered new areas of carcinoma in situ, including 3 who subsequently required cystectomy (2 after unsuccessful intravesical bacillus Calmette-Guerin therapy and 1 with a simultaneous invasive tumor). One patient underwent transurethral resection of the prostate for carcinoma in situ of the prostatic urethra, which subsequently was shown to be limited to mucosa and not involving the deeper ducts nor the stroma. Of the remaining 11 patients 1 died of unrelated disease and 2 suffered recurrent papillary transitional cell carcinoma treated successfully with a combination of intravesical bacillus Calmette-Guerin therapy and resection. The other 8 patients have remained free of tumor. None of the 15 patients had metastatic cancer. We believe that these results support the durability of response after induction mitomycin C therapy. We stress the necessity for prolonged close followup to detect recurrent tumor and to avoid metastatic disease. PMID- 2104638 TI - Clinical study of leuprolide depot formulation in the treatment of advanced prostate cancer. The Leuprolide Study Group. AB - In a phase III, open, multicenter study we evaluated the safety and efficacy of the depot formulation of leuprolide (7.5 mg. injected intramuscularly every 4 weeks) in patients with stage D2 prostate cancer who had not previously received systemic treatment. Serum testosterone, luteinizing hormone and plasma leuprolide levels were monitored during the 24-week study period. Median interval to onset of castrate testosterone levels was 21 days and mean testosterone levels decreased to within the castrate range by week 3 of treatment. After onset of castrate levels there were no escapes (defined as 2 consecutive values of greater than 50 ng./dl.) of testosterone levels during the 24 weeks. Suppression of testosterone did not differ significantly from that observed in patients receiving the daily subcutaneous injection of leuprolide acetate in the first 24 weeks of another study. Objective response (no progression) to treatment occurred in 81% of 53 evaluable patients and adverse (related and unrelated) events were reported in 45 of the 56 patients. The response rate and incidence of adverse events in this study did not differ significantly from those occurring with the daily formulation. We conclude that the depot formulation of leuprolide is safe and effective in the treatment of advanced prostatic cancer, and that the safety and efficacy of this formulation do not differ significantly from those of the daily subcutaneous formulation. PMID- 2104639 TI - Midwest symposium seeks therapeutic answers to global AIDS problem. PMID- 2104640 TI - Principles of educational outreach ('academic detailing') to improve clinical decision making. AB - With the efficacy and costs of medications rising rapidly, it is increasingly important to ensure that drugs be prescribed as rationally as possible. Yet, physicians' choices of drugs frequently fall short of the ideal of precise and cost-effective decision making. Evidence indicates that such decisions can be improved in a variety of ways. A number of theories and principles of communication and behavior changes can be found that underlie the success of pharmaceutical manufacturers in influencing prescribing practices. Based on this behavioral science and several field trials, it is possible to define the theory and practice of methods to improve physicians' clinical decision making to enhance the quality and cost-effectiveness of care. Some of the most important techniques of such "academic detailing" include (1) conducting interviews to investigate baseline knowledge and motivations for current prescribing patterns, (2) focusing programs on specific categories of physicians as well as on their opinion leaders, (3) defining clear educational and behavioral objectives, (4) establishing credibility through a respected organizational identity, referencing authoritative and unbiased sources of information, and presenting both sides of controversial issues, (5) stimulating active physician participation in educational interactions, (6) using concise graphic educational materials, (7) highlighting and repeating the essential messages, and (8) providing positive reinforcement of improved practices in follow-up visits. Used by the nonprofit sector, the above techniques have been shown to reduce inappropriate prescribing as well as unnecessary health care expenditures. PMID- 2104641 TI - Glucose inhibits myo-inositol uptake and reduces myo-inositol content in cultured rat glomerular mesangial cells. AB - Although activation of polyol pathway has been proposed as one of the etiologic factors of diabetic complications, precise mechanism of the effect of polyol accumulation is still unclear. In order to test the hypothesis that there is an association of polyol pathway with myo-inositol metabolism, we measured myo inositol content in cultured rat glomerular mesangial cells. By exposing the cells to high concentrations of glucose, intracellular myo-inositol content was reduced from 12.39 +/- 0.64 nmol/mg protein at 0 mmol/L glucose to 6.54 +/- 0.38 nmol/mg protein at 27.5 mmol/L glucose and 4.88 +/- 0.43 nmol/mg protein at 55 mmol/L glucose. This decrease of myo-inositol content was partially prevented by co-incubation with aldose reductase inhibitor, sorbinil. To examine further the mechanism of myo-inositol depletion, myo-inositol uptake by mesangial cells was studied. Major myo-inositol uptake process was sodium-dependent, saturable, and ouabain sensitive with Vmax of 171 pmol/mg protein/20 min and Km of 33 mumol/L. Sodium-dependent myo-inositol uptake was significantly inhibited by glucose in a dose-dependent manner only when glucose was present during uptake experiment, and kinetic analysis revealed the inhibition was competitive. Aldose reductase inhibition failed to prevent inhibitory effect of glucose on myo-inositol uptake. These data suggest that myo-inositol content of glomerular mesangial cells, which is reduced by high concentrations of glucose, is maintained by two processes: a glucose-sensitive but sorbitol-insensitive process, sodium-dependent myo-inositol uptake; and a sorbitol (aldose reductase) sensitive process, myo-Inositol depletion under high glucose condition may induce dysfunction of mesangial cells seen in diabetes. PMID- 2104642 TI - Effect of alcohol dose on plasma lipoprotein subfractions and lipolytic enzyme activity in active and inactive men. AB - Controversy as to which lipoprotein subfraction of high-density lipoprotein (HDL) increases during alcohol consumption prompted the current study of the effects of two alcohol doses over varying time intervals on plasma lipoproteins and lipolytic enzymes. Measurements were made in 49 healthy men before and after three weeks of abstinence from alcohol and after consumption of one or three 12 ounce cans of beer per day. We found that HDL (10%), HDL2 (14%), and HDL3 (9%) cholesterol, and apolipoprotein A-I (7%) decreased with abstinence from alcohol and then increased with its consumption. These increases were not significant until after 3 weeks of daily alcohol intake, but they were significant in both the one-can and three-cans of beer per day groups. In the 23 inactive subjects HDL and HDL2 cholesterol decreased with abstinence but did not increase significantly with alcohol intake. Lipolytic enzymes were not changed by alcohol manipulation, but the level of lipoprotein lipase was higher and that of hepatic lipase was lower at each measurement point in the 26 habitually active versus the 23 inactive subjects. Adjustment for weight or skinfold thickness did not affect lipoprotein changes over time within groups but did eliminate many of the differences between activity groups. Alcohol consumption seems to be related to possibly beneficial influences on plasma HDL and HDL2 cholesterol, and may thus impact the risk of heart disease. PMID- 2104643 TI - Insulin-like growth factors I and II are present in the skeletal tissues of ten vertebrates. AB - Previous studies have shown that insulin-like growth factor I and insulin-like growth factor II (IGF I and IGF II) constitute an important family of skeletal growth-regulating peptides. We undertook this study to determine if, as in the case of sera in various animals, IGF I and IGF II are conserved in the skeletal tissues of various vertebrates. Skeletal tissues of ten animals representing five of the six vertebrate classes were studied: monkey, dog, sheep, adult mice, neonatal mice, chicken, lizard, frog, trout, and shark. The skeletal tissues were pulverized and demineralized with 10% ethylenediaminetetraacetic acid (pH 7.0) to extract the soluble matrix proteins. The tissue extracts were concentrated, dialized, and subjected to specific human IGF assays. IGF I and IGF II were measured with a radioimmunoassay and a radioreceptor assay, respectively. We found that 1) there are detectable human IGF I- and II-like substances in all extracts, 2) IGF values obtained in the skeletal extracts were not caused by binding protein artifacts, 3) in general there is more IGF II than IGF I, and 4) the skeletal tissue levels of the IGFs are comparable with their respective serum levels. We conclude that, in the skeletal tissues of vertebrates, the IGFs are conserved and may be important regulators of osteogenesis. PMID- 2104644 TI - Percutaneous endoscopic gastrostomy: a two-year experience. AB - The results of percutaneous endoscopic gastrostomy in 25 patients who required enteral alimentation when feeding by mouth was not possible is reported. The procedure was successful on 30 occasions, with a low incidence of major complications. Endoscopic gastrostomy is a simple, less expensive alternative to surgical gastrostomy with a lower morbidity and mortality. PMID- 2104645 TI - What every doctor should know about economics. Part 1. The benefits of costing. PMID- 2104646 TI - Cardiopulmonary complications of mitomycin-C. PMID- 2104647 TI - Interferon for chronic viral hepatitis. PMID- 2104648 TI - Systemic administration of radionuclides in neuroblastoma as planned radiotherapeutic intervention. PMID- 2104649 TI - Group A beta-hemolytic streptococcal pharyngitis among U.S. Air Force trainees- Texas, 1988-89. PMID- 2104650 TI - Epidemic meningococcal disease--Kenya and Tanzania: recommendations for travelers, 1990. PMID- 2104651 TI - Update: eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan- United States, as of January 9, 1990. PMID- 2104652 TI - Group A beta-hemolytic streptococcal bacteremia--Colorado, 1989. PMID- 2104653 TI - Chronic disease reports: deaths from nine chronic diseases--United States, 1986. PMID- 2104654 TI - Years of potential life lost before ages 65 and 85--United States, 1987 and 1988. PMID- 2104655 TI - Update: Ebola-related filovirus infection in nonhuman primates and interim guidelines for handling nonhuman primates during transit and quarantine. PMID- 2104656 TI - Increase in National Hospital Discharge Survey rates for septicemia--United States, 1979-1987. PMID- 2104657 TI - Multiple, compensatory regulatory elements specify spermatocyte-specific expression of the Drosophila melanogaster hsp26 gene. AB - The hsp26 gene of Drosophila melanogaster is expressed in six tissues during development and in a tissue-general response to heat shock. To be able to compare tissue-specific and heat-induced mechanisms of hsp26 expression, we have begun an analysis of the sequences involved in the spermatocyte-specific expression of the hsp26 gene by using germ line transformation. hsp26 mRNA synthesized in the spermatocytes has the same start site as sites previously demonstrated for nurse cell-specific and heat-induced mRNAs. Three regions of the hsp26 gene (nucleotides -351 to -135, -135 to -85, and +11 to +632) were able to stimulate spermatocyte-specific expression when fused with promoter sequences (nucleotides 85 to +11) that alone were insufficient to stimulate expression. These stimulatory regions appear to contain elements that provide redundant functions. While each region was able to stimulate expression independently, the deletion of any one region from a construct was without consequence as long as another compensatory region(s) was still present. There must reside, at a minimum, two independent spermatocyte-specifying elements within the sequences that encompass the three stimulatory regions and the promoter. At least one element is contained within sequences from -351 to -48. This region, in either orientation, can stimulate spermatocyte-specific expression from a heterologous promoter. A second element must reside in sequences from -52 to +632, since these sequences are also sufficient to direct spermatocyte-specific expression. PMID- 2104658 TI - Regulatory elements mediating transcription from the Drosophila melanogaster actin 5C proximal promoter. AB - The major cytoskeletal actin gene of Drosophila melanogaster, the actin 5C gene, has two promoters, the proximal one of which controls constitutive synthesis of actin in all growing tissues. To locate regulatory elements required for constitutive activity of the proximal promoter, mutants of this promoter were fused to the bacterial chloramphenicol acetyltransferase gene and assayed for transient expression activity in cultured Drosophila embryonic Schneider line 2 cells. An essential regulatory element has been located 313 base pairs upstream from the cap site. Deletion of this element lowered expression to one-third of the wild-type level. The element has the sequence AAGTTGTAGTTG, as shown by protein-binding footprinting with the reagent methidiumpropyl-EDTA-Fe(II). This element is probably not a general one, since it was not detected in a search of the published 5'-flanking sequences of 27 Drosophila genes. In addition to this regulatory element, there are five GAGA elements in the actin 5C proximal promoter, some or all of which are essential for the promoter activity as shown by an in vivo competition assay. Although this promoter has no classical TATA element, there is an essential promoter region about 35 base pairs upstream from the cap site that could be a TATA surrogate. The promoter also shows sequences homologous to the alcohol dehydrogenase factor 1-binding site and to the core of the vertebrate serum response element, but mutations of these sites did not affect promoter activity in transient expression assays. PMID- 2104659 TI - Overexpression of the STE4 gene leads to mating response in haploid Saccharomyces cerevisiae. AB - The STE4 gene of Saccharomyces cerevisiae encodes the beta subunit of the yeast pheromone receptor-coupled G protein. Overexpression of the STE4 protein led to cell cycle arrest of haploid cells. This arrest was like the arrest mediated by mating pheromones in that it led to similar morphological changes in the arrested cells. The arrest occurred in haploid cells of either mating type but not in MATa/MAT alpha diploids, and it was suppressed by defects in genes such as STE12 that are needed for pheromone response. Overexpression of the STE4 gene product also suppressed the sterility of cells defective in the mating pheromone receptors encoded by the STE2 and STE3 genes. Cell cycle arrest mediated by STE4 overexpression was prevented in cells that either were overexpressing the SCG1 gene product (the alpha subunit of the G protein) or lacked the STE18 gene product (the gamma subunit of the G protein). This finding suggests that in yeast cells, the beta subunit is the limiting component of the active beta gamma element and that a proper balance in the levels of the G-protein subunits is critical to a normal mating pheromone response. PMID- 2104660 TI - The Drosophila Hrb98DE locus encodes four protein isoforms homologous to the A1 protein of mammalian heterogeneous nuclear ribonucleoprotein complexes. AB - The Drosophila Hrb98DE locus encodes proteins that are highly homologous to the mammalian A1 protein, a major component of heterogeneous nuclear ribonucleoprotein (RNP) particles. The Hrb98DE locus is transcribed throughout development, with the highest transcript levels found in ovaries, early embryos, and pupae. Eight different transcripts are produced by the use of combinations of alternative promoters, exons, and splice acceptor sites; the various species are not all equally abundant. The 3'-most exon is unusual in that it is completely noncoding. These transcripts can potentially generate four protein isoforms that differ in their N-terminal 16 to 21 amino acids but are identical in the remainder of the protein, including the RNP consensus motif domain and the glycine-rich domain characteristic of the mammalian A1 protein. We suggest that these sequence differences could affect the affinities of the proteins for RNA or other protein components of heterogeneous nuclear RNP complexes, leading to differences in function. PMID- 2104661 TI - Copy choice mechanism of immunoglobulin heavy-chain switch recombination. AB - The immunoglobulin heavy-chain switch is mediated by a recombination event between DNA switch regions associated with donor and recipient constant-region genes. We have determined that the mutations which can be found in some switch regions after recombination appear to arise on only one strand of DNA. This result suggests that switch recombination involves error-prone synthesis of one DNA strand and ligation of the other strand from preexisting DNA. PMID- 2104662 TI - A gene that encodes a protein consisting solely of zinc finger domains is preferentially expressed in transformed mouse cells. AB - We describe the cloning and characterization of the mouse MOK-2 gene, a new member of the Kruppel family of zinc finger proteins. Sequencing of both cDNA and genomic clones showed that the predicted MOK-2 protein consists of seven zinc finger domains with only five additional amino acids. The finger domains of MOK-2 are highly homologous to one another but not to those of other zinc finger proteins. MOK-2 is preferentially expressed in transformed cell lines, brain tissue, and testis tissue. Its possible role in cellular transformation is discussed. PMID- 2104663 TI - Lipopolysaccharide-unresponsive mutant pre-B-cell lines blocked in NF-kappa B activation. AB - NF-kappa B activation is a crucial late step in the induction of immunoglobulin kappa light-chain gene expression in pre-B cells by lipopolysaccharide (LPS). We have analyzed NF-kappa B activation in three independent mutant lines of 70Z/3 pre-B cells which are unresponsive to LPS. All three variant cell lines failed to activate NF-kappa B when induced with LPS or the phorbol ester 12-O tetradecanoylphorbol 13-acetate. However, all three cell lines contained functional NF-kappa B, as revealed by detergent treatment of cytoplasmic extracts. Moreover, cycloheximide induced limited activation of NF-kappa B comparable to that in wild-type 70Z/3 pre-B cells in two of the three variant lines. These results indicate that the mutations blocking kappa gene induction in these variant 70Z/3 pre-B-cell lines affect NF-kappa B activation. PMID- 2104664 TI - Leukemia following chemotherapy for ovarian cancer. AB - An international collaborative group of cancer registries and hospitals identified 114 cases of leukemia following ovarian cancer. We investigated the possible etiologic role of chemotherapy, radiotherapy, and other factors, using a case-control study design, with three controls matched to each case of leukemia. Chemotherapy alone was associated with a relative risk of 12 (95 percent confidence interval, 4.4 to 32), as compared with surgery alone, and patients treated with both chemotherapy and radiotherapy had a relative risk of 10 (95 percent confidence interval, 3.4 to 28). Radiotherapy alone did not produce a significant increase in risk as compared with surgery alone. The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known. PMID- 2104665 TI - Treatment of visceral leishmaniasis with pentavalent antimony and interferon gamma. AB - Acute visceral leishmaniasis is associated with an antigen-specific immunosuppression of mononuclear cells as evidenced by defective in vitro production of interferon gamma. We evaluated treatment with recombinant human interferon gamma in combination with conventional pentavalent antimony therapy in patients with visceral leishmaniasis. Six of eight patients with visceral leishmaniasis (mean duration, 17 months) that had been unresponsive to multiple courses of pentavalent antimony responded to treatment with recombinant human interferon gamma (100 to 400 micrograms per square meter of body-surface area per day) in addition to pentavalent antimony (20 mg per kilogram of body weight per day) for 10 to 40 days. The other two patients improved initially but then relapsed and required treatment with amphotericin B. Eight of nine additional patients with previously untreated severe visceral leishmaniasis were also successfully treated with the combination of interferon gamma and pentavalent antimony. The 14 patients who responded to this regimen had marked improvement in symptoms and in measures of anemia and leukopenia, as well as weight gain, a decrease in spleen size, and an absence or reduction of leishmanias in splenic aspirates. These patients had no recurrence of illness after a mean (+/- SE) follow-up of 8 +/- 1 months. Fever was the only major side effect of interferon gamma. We conclude that the combination of interferon gamma and pentavalent antimony is effective in treating seriously ill patients with refractory or previously untreated visceral leishmaniasis. PMID- 2104666 TI - The increased needs of patients in nursing homes and patients receiving home health care. AB - To evaluate the effects of Medicare's prospective payment system and Medicaid's preadmission regulations on long-term care, we constructed clinical profiles in 1982 and 1986 of about 500 randomly selected patients from each of three types of facilities: nursing homes with relatively high proportions of Medicare patients (high-Medicare nursing homes; n = 23), traditional nursing homes (n = 19), and home health agencies (n = 18). Data were obtained directly from the care givers on the medical problems, problems requiring skilled nursing, and functional problems of these representative patients from 12 states. For Medicare patients in high-Medicare nursing homes, the prevalence of medical problems and problems requiring skilled nursing increased substantially, whereas the prevalence of functional problems remained relatively unchanged. For example, from 1982 to 1986 there was a marked increase in the frequency of tube feedings (21 to 29 percent), oxygen use (6 to 14 percent), urinary tract infection (7 to 13 percent), and diastolic hypertension (1 to 10 percent), but not difficulty in eating (48 to 51 percent) or speaking (28 to 29 percent). In contrast, in traditional nursing homes there was an increase in the prevalence of functional disability, but virtually no change in that of problems requiring medical and skilled nursing care. In home health care the functional care needs of Medicare patients increased significantly, and there was a slight increase in the prevalence of problems requiring medical and skilled nursing care. We conclude that from 1982 to 1986 the needs of patients in long-term care increased substantially. This trend appears to result from Medicare's prospective payment system, which encourages earlier hospital discharge to long-term care settings, and from Medicaid's policy of de-institutionalization. Meeting this greater need for care will be costly. We require a better system of reimbursing for long-term care and ensuring its quality. PMID- 2104667 TI - Immunotherapy for parasitic disease. PMID- 2104668 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 3-1990. A 66-year-old woman with Waldenstrom's macroglobulinemia, diarrhea, anemia, and persistent gastrointestinal bleeding. PMID- 2104669 TI - Economies of scale, physician volume for neurosurgery patients, and the diagnosis related group prospective hospital payment system. AB - Hospitals face an increasingly competitive environment in the era of diagnostic related group (DRG) prospective pricing. Further reductions in Medicare outlays relative to hospital costs are likely, given the looming federal deficit. We analyzed the relationship of individual neurosurgical volume, hospital costs, and outcome. All neurosurgical patients (n = 1002) treated for a 3-year period at our large academic medical center were grouped into those treated by low-volume neurosurgeons versus those treated by high-volume neurosurgeons (arbitrarily defined by us); 95% of patients admitted for neurosurgical procedures fit into one of these two categories. Patients of low-volume neurosurgeons had higher hospital costs (even after correction for DRG case-mix and severity of illness) (P less than 0.01), a much worse financial position under DRGs (P less than 0.01), but a similar outcome for both emergency and nonemergency admissions when compared to patients of higher volume neurosurgeons. Pearson correlation showed an inverse relationship between declining cost per patient and increasing neurosurgical volume for both nonemergency patients -0.340 (P less than 0.0001), and emergency patients, -0.321 (P less than 0.0001). These findings suggest that the volume of neurosurgical procedures performed by an individual neurosurgeon is related to hospital resource utilization. This study also suggests that the DRG prospective payment system could provide incentives that may affect both neurosurgical practice and the access to neurosurgical care. PMID- 2104671 TI - RUGs (Resource Utiliation Groups): implications for staff development. PMID- 2104670 TI - Interim nursing management as temporary employment. PMID- 2104672 TI - Technology, its assessment, and nursing. AB - Technology assessment provides nurses with the knowledge they need to participate in decisions about the use of health care technology. PMID- 2104673 TI - Influence of caloric restriction and exercise on tumorigenesis in rats. AB - Underfeeding or caloric restriction have been shown to inhibit the growth of spontaneous, transplanted, or chemically induced tumors in rats and mice. At 40% caloric restriction, growth of 7,12-dimethylbenz(a)anthracene-induced mammary and 1,2-dimethylhydrazine-induced colonic tumors is inhibited significantly even when the restricted diet contains twice as much fat as the control diet. Some inhibitory effects become evident even at 10% caloric restriction. In studies involving high fat diets, we find that rats receiving 20% fat ad libitum exhibit significantly higher 7,12-dimethylbenz(a)anthracene-induced mammary tumor incidence, multiplicity, and weight than rats ingesting the same amount of fat daily, but in a diet containing 25% fewer calories. In a study of intermittent ad libitum and restrictive feedings, chemically induced tumorigenicity varies inversely with feed efficiency. Exercise has also been shown to inhibit tumor growth. Sedentary rats fed ad libitum have a 108% higher incidence of 1,2 dimethylhydrazine-induced colon tumors than rats fed ad libitum but subjected to vigorous treadmill exercise. Caloric flux (either reduced intake or increased outflow) appears to reduce tumorigenicity in rodents. PMID- 2104674 TI - Blood platelets and schistosome egg excretion. AB - The eggs of helminths of the Schistosoma genus require to be extravasated in order to continue the life cycle of the parasite. The possible mode by which this takes place was investigated in a mouse model. Suppression of platelet activity in Schistosoma mansoni-infected mice by administering rabbit anti-mouse platelet serum or a selection of "antiplatelet drugs" resulted in a significant reduction of parasite egg excretion. This reduction was best achieved when antiplatelet agents were administered just before the onset of parasite egg excretion. The association between parasite eggs and platelets was illustrated in vivo and in vitro where platelet aggregates on egg surfaces were seen in both light and electron microscopy. In addition, eggs that had been isolated from infected mouse tissues induced platelet aggregation in whole mouse blood, and this was inhibited by preincubation with the beta-lactam antibiotic, ticarcillin. Isolated eggs were also capable of inducing ex vivo platelet aggregation in mice, which was dependent on presensitization with eggs. These data suggest a role for platelets in the extravasation and excretion of parasite eggs in schistosomiasis. PMID- 2104675 TI - Real-time follow-up of 5-fluorouracil metabolism in the liver of tumor patients by means of F-19 MR spectroscopy. AB - Intraarterial 5-fluorouracil (5-FU) chemotherapy in eight patients, one with primary and seven with secondary liver tumors, was monitored by means of in vivo fluorine-19 magnetic resonance (MR) spectroscopy. F-19 MR spectra were obtained with surface coils and included signal contributions from both liver and tumor tissue. The time course of the relative concentrations of 5-FU and its major catabolite, alpha-fluoro-beta-alanine (FBAL), was followed for up to 100 minutes after the start of drug administration. The time constants for the kinetics of 5 FU ranged from 8 to 75 minutes, whereas the time constants for FBAL were either approximately 15 or 50 minutes. A broad peak comprising nucleoside and nucleotide anabolites of 5-FU was detected in one patient. These investigations demonstrate the feasibility of short-term therapy monitoring with F-19 MR spectroscopy and that catabolites and anabolites of 5-FU can be observed separately. However, since no F-19 MR spectroscopy localization sequence is available at present, the contributions to the total MR signal from normal liver and tumor tissue cannot be discriminated. PMID- 2104676 TI - Stage I and II breast carcinoma: treatment with limited surgery and radiation therapy versus mastectomy. AB - Between 1980 and 1986, 2,140 patients with surgical stage I or II breast carcinoma were treated including 1,179 patients with T1-2N0 disease and 961 patients with T1-2N1 disease. Among the 1,179 patients without node involvement, 215 underwent limited surgery (complete excision and axillary node dissection) and radiation therapy; 964 patients underwent modified radical mastectomy only. Of the 961 patients with node involvement, 106 were treated by means of limited surgery and radiation therapy; of these, 48 also received chemotherapy. The remaining 855 patients underwent mastectomy; of these, 381 also received chemotherapy and/or hormone therapy. The 5-year survival rates for patients with no node involvement were 96% for the group treated by means of limited surgery and radiation therapy and 88% for the group treated by means of mastectomy (P greater than .05). The 5-year survival rates for patients with node involvement were 96% for the group treated by means of limited surgery and radiation therapy with or without chemotherapy and 77% for the group treated by means of mastectomy with or without chemotherapy (P less than .01). This study demonstrates no disadvantage from treatment by means of limited surgery and radiation therapy and suggests that adjuvant radiation therapy may be important in increasing survival among patients with T1-2 breast carcinoma and positive axillary nodes. PMID- 2104677 TI - Flexible protective gloves: the emperor's new clothes? AB - The risk of developing skin cancer is estimated for interventional radiologists who do and do not wear thin, flexible protective leaded gloves. The use of these gloves is extremely expensive in terms of dollars per potential cancer prevented. Good radiographic practice without the use of flexible protective gloves provides adequate protection. PMID- 2104678 TI - Evidence for a novel thioredoxin-like catalytic property of gonadotropic hormones. AB - It has been proposed that dithiol-disulfide interchange and oxidation-reduction reactions may play a role in hormone-induced receptor activation. Inspection of the sequences of the gonadotropic hormones revealed a homologous tetrapeptide (Cys-Gly-Pro-Cys) between the beta subunit of lutropin (LH) and the active site of thioredoxin (TD). The beta subunit of follitropin (FSH) has a similar sequence (Cys-Gly-Lys-Cys). Thioredoxin is a ubiquitous protein serving as an electron donor for ribonucleotide reductase, but it also exhibits disulfide isomerase activity. The catalytic activity of TD was assayed by its ability to reactivate reduced and denatured ribonuclease. In this assay, the purified ovine FSH and bovine LH preparations tested were approximately 60 and approximately 300 times, respectively, as active as TD on a molar basis. This heretofore unsuspected catalytic property of FSH and LH may be important in understanding their mechanism of receptor activation and signal transduction. PMID- 2104679 TI - Pushing the envelope of life. PMID- 2104680 TI - Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts. AB - Normal cells in culture invariably undergo senescence, whereby they cease proliferation after a finite number of doublings. Irreversible changes in gene expression occurred in senescent human fetal lung fibroblasts: a non-cell cycle regulated mRNA was partially repressed; an unusual polyadenylated histone mRNA was expressed; although serum induced c-H-ras, c-myc, and ornithine decarboxylase mRNA normally, ornithine decarboxylase activity was deficient; and serum did not induce mRNA for a replication-dependent histone and for the c-fos proto-oncogene. The loss of c-fos inducibility was the result of a specific, transcriptional block. The results suggest that senescent fibroblasts were unable to proliferate because of, at least in part, selective repression of c-fos; moreover, the multiple changes in gene expression support the view that cellular senescence is a process of terminal differentiation. PMID- 2104681 TI - Cholecystokinin prevents parenteral nutrition induced biliary sludge in humans. AB - Long term total parenteral nutrition (TPN) induces biliary sludge and formation of gallstones. Cholecystectomy is hazardous in these patients because of the underlying medical problems. Therefore, a randomized, double-blind controlled study was designed to test the hypothesis that daily administration of cholecystokinin-octapeptide (CCK-OP) prevents the formation of biliary sludge in humans receiving long term TPN. Adult patients receiving TPN for more than 21 consecutive days were studied. After randomization of 15 patients, the study was concluded because statistical significance was achieved. Eight patients received saline solution (placebo) intravenously and seven received CCK-OP (50 nanograms per kilogram) intravenously over a ten minute period daily. The groups were similar with respect to age, sex, diagnosis, liver function tests, amylase levels, total TPN time and time of study. All of the patients underwent weekly ultrasound studies. Volume and emptying studies of the gallbladder in response to the study drug were performed after one week. None of the patients receiving CCK OP had sludge whereas five of eight of the patients receiving placebo had sludge (p less than 0.02). The results of emptying studies showed significant contraction of the gallbladder in those in the CCK-OP group but not in the placebo group. These data suggest that CCK-OP given intravenously daily prevents TPN induced stasis and sludge of the gallbladder. We conclude that CCK-OP should be used as routine prophylaxis against biliary sludge and formation of gallstones in patients receiving long term TPN. PMID- 2104682 TI - Characterization of an HIV-1 point mutant blocked in envelope glycoprotein cleavage. AB - The envelope proteins of retroviruses are derived from a polypeptide precursor protein by cleavage adjacent to a cluster of basic amino acids. Site-specific mutagenesis was used to construct a mutant of the human immunodeficiency virus type 1 (HIV-1) in which the arginine residue at the carboxy-terminus of the gp120 was changed to a threonine residue. This single substitution was sufficient to abolish all detectable cleavage of the gp160 envelope precursor polypeptide as well as virus infectivity. The gp160 was produced in normal quantities from a biologically active clone of the mutant virus after transfection into cos-1 cells. The mutant gp160 contained N-linked oligosaccharide chains with mannose rich cores similar to those of the gp160 produced by the wild-type clone. Immunofluorescence assays showed that gp160 was transported to the surface of transfected CD4+ HeLa cells. No envelope proteins of known size could be detected in the media of cells transfected with the mutant virus, suggesting that functional virions were not formed. Binding of the mutant gp160 to the CD4 receptor molecule was unimpaired. Despite this and the presence of gp160 on the cell surface, neither growth of mutant-transfected CD4+ HeLa cells nor cocultivation of transfected cos-1 cells with H9 cells resulted in significant syncytium formation. The data indicate that the carboxy-terminal arginine residue of HIV-1 gp120 is necessary for envelope protein cleavage and suggest cleavage is important in the virus life cycle in both functional virus release and membrane fusion. PMID- 2104683 TI - Interferon-gamma regulation of major histocompatibility class I gene expression in rat cells containing the adenovirus 12 E1A oncogene. AB - Interferon-gamma (IFN gamma) treatment of cells expressing the Ad12 E1A oncogene results in an increase in MHC class I antigen expression. The effect of IFN gamma upon both the steady-state level of class I mRNA and the in vitro rate of initiation of transcription of class I genes was studied in a rat cell line containing the Ad12 E1A gene. Results obtained showed a marked increase in steady state level of cytoplasmic class I mRNA; however, a concomitant increase in the rate of transcription of class I genes was not observed. In contrast IFN gamma was shown to markedly increase the rate of transcription of class I genes in primary baby rat kidney cells. PMID- 2104684 TI - Molecular characterization of the RNA S segment of nephropathia epidemica virus strain Hallnas B1. AB - The S segment RNA of nephropathia epidemica virus (NEV) strain Hallnas B1 was isolated by molecular cloning of the corresponding cDNA. The RNA is 1785 nucleotides long with the 3' and 5' termini being complementary for 23 bases. The viral messenger-sense RNA contains one major open reading frame (ORF) with a coding capacity of 433 amino acids encoding a 49-kDa polypeptide. Compared to the Hantaan S segment cDNA sequence there is a nucleotide homology of 60 and 61% at the amino acid level. Many of the amino acid differences are conservative exchanges. The C-termini of the NEV and Hantaan nucleocapsid proteins are nearly identical and the hydrophilicity profiles are very similar. In contrast, the following differences are significant: The calculated isoelectric points of the NEV and Hantaan nucleocapsid proteins are 5.6 and 6.7, respectively. The most prominent antigenic determinants predicted by the hydrophilicity profiles are located close to the C-terminus of NEV and close to the N-terminus of Hantaan virus nucleocapsid polypeptides. PMID- 2104685 TI - Expression of the amyloid beta-protein precursor gene. PMID- 2104686 TI - Molecular relation of amyloid filaments and paired helical filaments in Alzheimer's disease. PMID- 2104687 TI - Analysis of the beta-amyloid protein precursor of Alzheimer's disease: mRNAs and protein products. PMID- 2104688 TI - Diagnosis and care of Alzheimer's disease patients: a European perspective. PMID- 2104689 TI - CT and sonographically guided needle biopsy: current techniques and new innovations. PMID- 2104690 TI - Blue rubber bleb nevus syndrome: CT diagnosis of intussusception. PMID- 2104692 TI - The posterior intercostal approach for percutaneous renal procedures: risk of puncturing the lung, spleen, and liver as determined by CT. AB - A posterior intercostal approach is commonly used for percutaneous access to the upper poles of the kidney. However, the safety of this approach with respect to puncturing the intervening lung, pleura, liver, and spleen with the needle has been inferred only from a small series of patients without regard to the degree of respiration. To determine the possibility of puncturing these structures, we performed CT at both maximal inspiration and expiration and with sagittal reconstructions in 43 (27 supine and 16 prone) randomly selected patients. With expiration, the needle path was such that there was little risk to the spleen and liver from an 11th-12th posterior intercostal approach. However, the chance of transgressing the lung with this approach to the kidney was 29% on the right and 14% on the left. If done during maximal inspiration, the lung would be in the path of the needle in most patients. With a 10th-11th rib posterior intercostal approach, the chance of puncturing the lung was excessive regardless of the degree of respiration used. Our results show that the primary risk from a posterior 11th-12th rib intercostal approach to the upper renal collecting system is puncture of intervening lung, a complication that can be expected to occur in from 14% to 29% of patients. The risks from a posterior 10th-11th rib intercostal approach appear prohibitive. PMID- 2104691 TI - Sonographic detection of pneumoperitoneum in patients with acute abdomen. AB - We describe five patients who presented with an acute abdomen in whom pneumoperitoneum was first detected by sonography. All five subsequently were proved to have a perforated viscus. In all cases, the pneumoperitoneum was seen as an echogenic line with a posterior ring-down or reverberation artifact between the anterior abdominal wall and the anterior surface of the liver. The finding was shown best in the right upper quadrant with the patient in the left lateral decubitus position. The echoes caused by the pneumoperitoneum overlapped the echoes of the lung during inspiration, but the echoes were separate during expiration. The probable cause of pneumoperitoneum was determined with sonography in four of the five patients: three had perforation of duodenal ulcer and one had perforation of gastric cancer. The fifth patient had a perforated ileum, which was not evident on the sonogram. Our experience with these patients suggests that the detection of pneumoperitoneum on sonography in patients with an acute abdomen is an important sign of a perforated viscus. PMID- 2104693 TI - Surgical lateral ovarian transposition: CT appearance. PMID- 2104694 TI - Rotator cuff tears: diagnosis with sonography. AB - The purpose of this study was to determine the accuracy of sonography in the detection of rotator cuff tears. Eighty-one patients were referred by orthopedic specialists because of a clinical suspicion of rotator cuff tear. The standards of comparison were arthrography in 79 cases and surgery in two cases. The sonographic technique used was based on a review of the literature and experience gained by scanning normal subjects. The sonographic criteria for the diagnosis of a complete rotator cuff tear were a focal defect in the cuff or complete absence or nonvisualization of the cuff. All sonograms were interpreted prospectively without knowledge of arthrographic or surgical results. With arthrography as the standard of comparison for the diagnosis of rotator cuff tear, sonographic results included 15 true-positives, 52 true-negatives, eight false-negatives, and four false-positives. With surgery as the standard of comparison, the results were one true-positive and one true-negative sonogram. The sensitivity of sonography in detecting rotator cuff tear was 0.67, the specificity was 0.93, and the accuracy was 0.85. Our study found lower sensitivity and accuracy results for shoulder sonography than have been previously reported. PMID- 2104695 TI - Sonographic evaluation of bone production at the distraction site in Ilizarov limb-lengthening procedures. AB - The success of the Ilizarov distraction technique has resulted in a marked increase in the number of limb-lengthening and limb-straightening procedures performed for the correction of short and deformed limbs. This technique involves fracture of the bone and application of an external ring and bar support frame with circumferential screw threads and nuts, which allows systematic distraction of bone segments at a rate of 0.25 mm four times a day. During the procedure, the patient is encouraged to be ambulatory, as the strength of the frame allows weight bearing. Because of the limitations of plain radiographs in detecting the small amounts of new bone formation that occur at the distraction site in the early stages of healing, the success of the procedure cannot be determined for many weeks. The rate of distraction depends on the successful production of new bone in the distraction site. Early evaluation of new bone production is therefore important, because slow bone formation requires a decrease in distraction rate and vice versa. We examined 12 patients who had limb-lengthening procedures via the Ilizarov technique to determine if sonography could be used to detect early new bone formation at the distraction site. Our results show that new bone formation could be detected with sonography many weeks before its appearance on the radiograph. The sonographic appearance of new bone consists of echogenic foci within the distraction site, which become aligned in the longitudinal plane and which increase in number and size until they coalesce as echodense bone, which does not allow through-transmission of the ultrasound beam. In addition, sonograms showed 1.5-cm and 2-cm cysts within the distraction site in two patients in whom they were not visible on the radiographs. Timely percutaneous aspiration allowed continued normal bone generation. We conclude that sonography is useful for the detection of new bone formation at the distraction site in patients undergoing the Ilizarov procedure. PMID- 2104696 TI - The current role of tenography and bursography. PMID- 2104697 TI - Treatment of suppurative arthritis by percutaneous catheter drainage. AB - Percutaneous catheter drainage to treat suppurative arthritis was performed in five joints in five patients. Joints drained included the hip in two cases and one case each of a hip joint prosthesis, an ankle joint, and a glenohumeral joint. Organisms isolated from the joints included Staphylococcus aureus in one hip joint and the hip prosthesis, and Haemophilus influenzae in the ankle joint. Specific organisms were not isolated in the other hip joint or in the shoulder joint. Systemic antibiotic therapy was used in all five patients, and in two patients gentamicin was instilled through the catheters. Joint infection was managed successfully with catheter drainage and antibiotics in three patients. In all three cases, the range of motion was restored and the patients became free of pain after catheter drainage. These three patients remained asymptomatic at follow-up ranging from 3 weeks to 9 months. In two patients, percutaneous drainage failed. In one patient, the catheter positions could not be maintained and the catheters repeatedly became dislodged. In the other, superimposed osteomyelitis necessitated surgical debridement. No complications occurred. Our experience suggests that suppurative arthritis can be successfully treated with drainage of the joint via a percutaneous catheter in combination with antibiotic therapy. PMID- 2104698 TI - Ovarian teratomas: a comparison of the sonographic appearance in prepubertal and postpubertal girls. AB - Sonography was performed in 17 pediatric patients with 18 benign cystic teratomas of the ovary in order to compare the appearance of this entity in prepubertal and postpubertal girls. Particular attention was paid to the frequency of the characteristic features of this lesion, particularly mural nodules and acoustic shadowing. Of the eight lesions in children less than 13 years old, five were complex lesions and three were cystic. Mural nodules were found in three (38%) of eight lesions and acoustic shadowing in one (13%). Of the 10 lesions in the patients 13 years old or more, seven were complex and three were solid. Seven (70%) of 10 lesions contained a mural nodule, seven (70%) had acoustic shadowing, and one (10%) had a fluid/fluid level. Our experience suggests that typical sonographic features of ovarian teratomas occur more frequently in postpubertal than prepubertal girls. PMID- 2104699 TI - Sonography of facial features of alobar and semilobar holoprosencephaly. AB - Twenty-seven cases of alobar/semilobar holoprosencephaly were reviewed to determine and classify the associated facial abnormalities detected with prenatal sonography. All but one case were diagnosed prospectively with sonography. Facial abnormalities were present in 24 of 27 cases and were detected in 14 (58%) of 24 fetuses on prenatal sonography. Prenatal abnormalities detected by sonography included cyclopia (four of five), ethmocephaly (two of three), cebocephaly (one of three), midline cleft lip (four of eight), lateral cleft lip (two of two), and mild hypotelorism (one of three). One or more extrafacial anomalies were present in 14 (52%) of 27 fetuses. Other major structural anomalies detected prenatally by sonography included meningomyelocele (two of two), renal dysplasia (five of six), omphalocele (three of four), esophageal atresia (zero of three), and cardiac defects (one of seven). Chromosomal analysis revealed abnormal karyotype in 13 (50%) of the 26 fetuses in which it was performed; the most common abnormality was trisomy 13 (seven cases). The perinatal mortality rate was 89% (24 of 27); three neonates with holoprosencephaly were alive when discharged from the hospital. It is concluded that when a major cystic abnormality of the fetal brain is detected, prenatal sonographic analysis of midline facial defect may allow more definitive diagnosis of alobar or semilobar holoprosencephaly; affected fetuses often have other major structural abnormalities, and the outcome is nearly always fatal. PMID- 2104700 TI - Magnetic catheter for removal of magnetic foreign bodies. PMID- 2104702 TI - Synovial cysts of the lumbosacral spine: diagnosis by MR imaging. AB - Intraspinal synovial or ganglion cysts are uncommon lesions associated with degenerative lumbosacral spine disease. CT usually reveals cystic lesions adjacent to a facet joint, and they may show calcification. MR imaging of four surgically confirmed cases of intraspinal synovial cysts revealed subtle signal changes compared with CSF. Short TR/TE images showed the lesions to be slightly hyperintense in three cases and isointense in one case. Long TR/TE sequences revealed a hyperintense appearance in two cases and a hypointense appearance in the others. A peripheral rim of decreased signal on long TR/TE images probably reflects fine calcification or hemorrhage in the margins of the cysts. The multiplanar and contrast characteristics of MR make this technique well suited to the diagnosis of herniated disk, degenerative facet disease, and synovial cyst. PMID- 2104701 TI - Assessment of extradural degenerative disease with Gd-DTPA-enhanced MR imaging: correlation with surgical and pathologic findings. AB - To test whether gadolinium-DTPA-enhanced MR would increase the conspicuity of extradural degenerative disease in the previously unoperated patient, we prospectively studied a group of 30 patients with symptoms suggestive of disk disease. Surgical findings and pathologic correlations were used as an objective measure of accuracy. Gadolinium-DTPA increased the confidence of diagnosis at one of eight operated cervical levels (six patients) and changed the diagnosis from extradural degenerative disease to tumor in one patient. The mechanism of enhancement of the epidural space and peridiskal region appears to be related to accumulation of contrast material within the epidural venous plexus, as well as to epidural fibrosis associated with disk disruption and herniation. While the immediate clinical utility of gadolinium-DTPA for morphologic analysis seems limited to difficult cervical spine cases, the presence of enhancement as a marker of epidural fibrosis and attempted healing may prove to be of great importance in studying the natural history and basic pathophysiology of degenerative disk disease. PMID- 2104703 TI - MR imaging of Tolosa-Hunt syndrome. AB - The Tolosa-Hunt syndrome consists of painful ophthalmoplegia caused by cavernous sinus inflammation, which is responsive to steroid therapy. The MR features of 11 patients with the clinical diagnosis of Tolosa-Hunt syndrome were studied. Two patients had normal MR studies of the orbit and cavernous sinuses. In nine patients, abnormal signal and/or mass lesions were seen in the cavernous sinuses; in eight cases, the abnormality was hypointense relative to fat and isointense with muscle on short TR/TE images and isointense with fat on long TR/TE scans. Extension into the orbital apex was seen in eight cases. In six of nine cases the affected cavernous sinus was enlarged; in five of nine it had a convex outer margin. One patient had a thrombosed cavernous sinus and superior ophthalmic vein in addition to a cavernous sinus soft-tissue mass. The signal intensity of Tolosa Hunt syndrome in this limited series was similar to that of orbital pseudotumor and is confined to a limited differential diagnosis, which includes meningioma, lymphoma, and sarcoidosis. PMID- 2104704 TI - How to evaluate the radiology literature. PMID- 2104705 TI - Diagnosis of femoropopliteal venous thrombosis with MR imaging: a comparison of four MR pulse sequences. AB - In a prospective study, MR images were evaluated in seven patients with femoropopliteal venous thrombosis with symptoms of less than 5 days duration. T1 weighted (600/25 [TR/TE]), intermediate (2000/30), and T2-weighted (2000/100) spin-echo series and a gradient-recalled acquisition in the steady state (GRASS) series were compared. Using venography as the standard for diagnosis, we found GRASS to be the most sensitive of the MR techniques, showing thrombi in all patients. It provided good contrast between the low-intensity thrombus and high intensity flowing blood and also between thrombus and intermediate- or high intensity perivascular tissues. The T1-weighted series was the least sensitive technique. All thrombi showed heterogeneity in the transaxial image with differences in signal between the peripheral and central regions. A higher intensity signal in the center than in the periphery at some level of the thrombus was found in six of seven T2-weighted or GRASS images. Heterogeneity in the signal intensity was more frequent in distal portions of thrombi, whereas the most proximal extent was homogeneous in appearance in six of seven cases. The heterogeneous appearance may be related to the greater age of the distal thrombus, because deep venous thrombi are known to begin in the calf and extend proximally over time. We conclude, on the basis of our experience with a small number of patients, that the GRASS MR technique is more sensitive for detecting acute deep venous thrombosis than T1-weighted, intermediate, and T2-weighted MR images. PMID- 2104706 TI - Transcatheter embolization of a ruptured abdominal aortic stump. PMID- 2104707 TI - Simple technique for redirecting malpositioned central venous catheters. PMID- 2104709 TI - The Society of Uroradiology: abstracts from the 1989 meeting. Naples, Florida, September 23-24, 1989. PMID- 2104708 TI - Estimated fetal radiation dose from multislice CT studies. AB - It is often necessary to estimate the dose of radiation to a fetus from a series of CT scans. To assist in making this process easier and more accurate, we measured fetal doses in an adult anthropomorphic phantom for four CT scanners: Picker 1200, Siemens DRH, GE 9800, and GE 8800. Measurements were made at four kilovoltages (100, 120, 130, and 140 kVp), for 2-, 5-, 8-, and 10-mm thicknesses, for two scanning angles (360 degrees and 398 degrees) and for two patient orientations (prone and supine). The fetal-dose estimates are based on the CT dose index measured by using a pencil ionization chamber at the center position of a 16-cm-diameter cylindrical phantom. Comparison with data from other investigators shows reasonable agreement when phantom differences, X-ray tube output, and equipment calibration are considered. PMID- 2104711 TI - Low-attenuation mediastinal masses on CT. PMID- 2104710 TI - Hypersensitivity reaction during barium enema. PMID- 2104712 TI - Tuberculosis and peptic stricture of the esophagus. PMID- 2104713 TI - Inflammatory pseudotumor of the liver. PMID- 2104714 TI - Imaging investigation of urinary tract infection. PMID- 2104715 TI - Herniation of an ovarian cyst through the inguinal canal: diagnosis with CT. PMID- 2104716 TI - Directable cannula for gastrojejunal catheterization. PMID- 2104717 TI - Fatality from fine-needle aspiration biopsy of a hepatic hemangioma. PMID- 2104718 TI - The Gibbs phenomenon. PMID- 2104719 TI - Radiographic detection of esophageal malpositioning of endotracheal tubes. AB - Insertion of an endotracheal tube into the esophagus is an infrequent but life threatening complication of endotracheal intubation. This complication is difficult to detect on standard, anteroposterior, portable chest radiographs because the incorrectly placed endotracheal tube is usually projected over the tracheal air column. To evaluate the use of chest radiographs to detect the malposition, we performed a two-part study. First, we analyzed the findings on chest radiographs in six patients in whom an endotracheal tube had been inserted in the esophagus, and then we analyzed 328 portable chest radiographs of patients with both endotracheal and nasogastric tubes to determine the best radiographic position for identifying the exact location of an endotracheal tube. The findings in the six patients included projection of the tube lateral to the trachea (five patients), gastric distension (four patients), esophageal air (two patients), and deviation of the trachea by the balloon cuff (one patient). The study of the portable chest radiographs showed that the endotracheal tube position could be identified correctly in 81 (92%) of 88 of the films made with the patient in a 25 degrees right posterior oblique position. The trachea and esophagus were superimposed in 25 (96%) of 26 of the radiographs made with the head turned to the left and with the patient in a 25 degrees left posterior oblique projection. Our results show that by positioning patients for chest radiographs in a 25 degrees right posterior oblique position, the location of endotracheal tubes can be identified accurately. PMID- 2104720 TI - Visceral and nodal calcification in patients with AIDS-related Pneumocystis carinii infection. AB - Clinical and radiologic findings in nine patients with AIDS and disseminated Pneumocystis carinii infection were analyzed retrospectively. The diagnosis was confirmed by autopsy (five patients) and by biopsy (two patients). All nine had a history of P. carinii pneumonia. CT showed parenchymal calcifications in the spleen (seven patients), liver (six patients), kidneys (six patients), abdominal lymph nodes (three patients), adrenal glands (two patients), and mediastinal lymph nodes (one patient). Multiple punctate calcifications in the liver, spleen, kidneys, and/or adrenal glands were visible on plain films in three patients. Sonography showed diffuse tiny echogenic foci without shadowing in the liver, spleen, and kidneys. In one patient, CT showed multiple hypodense lesions in the spleen. P. carinii infection should be included in the differential diagnosis when calcifications or focal lesions are detected at one or more extrapulmonary sites in an immunodeficient patient, even if there is no history or evidence of P. carinii pneumonia. PMID- 2104721 TI - The anterior wall stripe of the left lower lobe bronchus on the lateral chest radiograph: CT correlative study. AB - We designed a study to determine whether thickening or effacement of the anterior wall stripe of the left lower lobe bronchus on the lateral chest radiograph implies adjacent disease, as it does for the posterior wall stripe of the right bronchus intermedius. The anterior wall stripe of the left lower lobe bronchus originates from the inferior anterior aspect of the end-on left bronchus and descends in a gentle posteriorly convex curve. The left lower lobe bronchus was identified on routine lateral chest films in 86 of 90 consecutive patients who also had chest CT. In those cases the anterior wall stripe was measured and categorized on chest films. On the CT scans, the length of the left lower lobe bronchus and its relationship to the left lower lobe artery and left upper lobe, lingular, and lower lobe veins were assessed. The presence of adjacent disease was noted. A complete anterior wall stripe was seen in 59 of 86 cases. It was effaced by anterior soft tissue in 15 of 86 cases; in 12 of 86 cases only the superior 0.5-1.5 cm was effaced. A normal anterior wall stripe was as thick as 12 mm in one case, but was 6 mm or less in 90%. Shapes other than linear were common. Anatomic variation accounted for nearly all of these findings. There was no focal abnormality in the 12 cases with partial effacement or in nine of the 15 cases with complete effacement; disease was significant in only two of these six. We concluded that thickening or effacement of the anterior wall stripe is an unreliable sign of disease. PMID- 2104722 TI - CT appearance of the retroaortic anastomoses of the azygos system. AB - The terminations of the hemiazygos and accessory hemiazygos veins can be mistaken for normal or enlarged posterior mediastinal lymph nodes on CT scans of the chest. These terminations are termed the retroaortic anastomoses by anatomists. We studied the CT appearances of these veins on scans of one cadaver and seven patients. We found that the retroaortic anastomoses usually were clearly recognizable because of their continuity with the hemiazygos or accessory hemiazygos vein. However, it is sometimes possible to mistake these vessels for lymph nodes, especially when only short segments of the vessel are visible on a CT image or when the vessel is not clearly opacified by contrast material. Familiarity with the CT appearances of the hemiazygos and azygous veins can prevent their being mistaken for normal or enlarged lymph nodes. PMID- 2104723 TI - CT and chest radiography are equally sensitive in the detection of pneumothorax after CT-guided pulmonary interventional procedures. AB - Pneumothorax is the most common complication after CT-guided pulmonary interventional procedures and should be promptly diagnosed and treated. Because it is easier to obtain CT scans than chest radiographs after CT-guided interventional procedures, it is important to know the sensitivity of CT in detecting pneumothoraces. To determine the sensitivity of CT for detecting procedure-induced pneumothoraces, we retrospectively reviewed 70 pulmonary interventional procedures performed under CT guidance. The sensitivity for detecting pneumothoraces with CT was compared with the detection rate with expiratory chest radiographs. Thirty-two (46%) of 70 procedures resulted in pneumothorax. Twenty-nine (91%) of the pneumothoraces were detected on CT scans and 27 (84%) were detected on chest radiographs. The difference between these two detection rates was not statistically significant (p less than .90). We conclude that postprocedure CT scans can replace expiratory chest radiographs for the detection of pneumothoraces after CT-directed pulmonary procedures. PMID- 2104724 TI - Life-threatening hemorrhage due to percutaneous transthoracic intervention: importance of the internal mammary artery. PMID- 2104725 TI - Lung hernia: radiographic features. AB - Lung hernia is an abnormal protrusion of the lung beyond the confines of the thoracic cage. Hernias are classified as cervical, intercostal, or diaphragmatic. Each of these types can be either congenital or acquired. Acquired hernias can be spontaneous, posttraumatic, or pathologic as a result of a neoplastic or inflammatory process. This report describes five cases of lung hernias. Two were congenital cervical hernias, detected as incidental findings on chest radiographs of infants. One was a posttraumatic intercostal hernia detected on a chest radiograph and confirmed with CT. The remaining two were acquired intercostal hernias at the site of prior chest-tube drainage of tuberculous empyemas. Although both of these were clearly shown on CT scans, only one was visible on chest radiographs. PMID- 2104726 TI - CT of blunt chest trauma. PMID- 2104727 TI - Dysphagia due to mediastinal fibrosis in advanced pulmonary tuberculosis. AB - Dysphagia in patients with pulmonary tuberculosis may be due to tuberculous esophagitis or compression of the esophagus by enlarged mediastinal lymph nodes or mediastinal fibrosis. We studied the clinical and radiologic findings in nine patients with advanced pulmonary tuberculosis who presented with dysphagia. In each patient, dysphagia first occurred while the patient was on antituberculous therapy. Chest radiographs in each case showed extensive tuberculous disease of the lung, affecting especially the left upper lobe. In addition, dense mediastinal pleural fibrosis was seen along the medial aspects of the upper thorax. Tomograms did not show mediastinal lymph node enlargement. Barium esophagograms showed extrinsic compression and various degrees of narrowing of the supracarinal part of the esophagus. No mucosal abnormality was seen on esophagoscopy. On the basis of these findings, the compression of the esophagus in these patients was attributed solely to tuberculous mediastinal fibrosis. The dysphagia remained constant in all patients except one, in whom worsening dysphagia improved after balloon dilatation. We conclude that mediastinal fibrosis is a significant cause of dysphagia in patients with advanced pulmonary tuberculosis. PMID- 2104728 TI - Differentiation of radiation fibrosis from recurrent neoplasia: a role for 31P MR spectroscopy? PMID- 2104729 TI - Effusion in the superior pericardial recess simulating a mediastinal mass. PMID- 2104730 TI - Ileoanal pouches: comparison of CT, scintigraphy, and contrast enemas for diagnosing postsurgical complications. AB - The value of CT of the pelvis, 111In-labeled leukocyte scintigraphy, and contrast enema (pouchography) for detecting postsurgical complications was assessed in 44 patients with total colectomy, rectal mucosectomy, and ileoanal pouches. Ileoanal pouches were created as reservoirs from an ileal loop that was anastomosed to the dentate line of the anus and stayed connected to the remainder of the ileum. This pouch preserves the normal defecatory pathway and eliminates disease-producing mucosa. A total of 57 sets of examinations revealed 22 cases of normal postoperative findings, 22 of pouchitis, 13 of abscess, and three of fistula. Overall sensitivity for detecting complications with pouchography was 60% (18 of 30 findings); with CT, 78% (28 of 36 findings); and with scintigraphy, 79% (23 of 29 findings). Pouchitis was best diagnosed by scintigraphy (sensitivity, 80%), followed by CT (sensitivity, 71%) and pouchography (sensitivity, 53%). Only CT correctly diagnosed all cases of abscess. Fistulas were frequently missed by all three methods. If tests were combined, the overall sensitivity rose to 93% for the combination CT/scintigraphy and to 86% for CT/pouchography, but did not improve for pouchography/scintigraphy (78%). For evaluation of complications in patients with ileoanal pouches, CT should be the initial test. If an abscess is found, no further tests are needed. If CT findings are negative, a scintigram should be obtained. Our data did not establish a clear role for pouchography. PMID- 2104731 TI - CT of the extrahepatic bile ducts: wall thickness and contrast enhancement in normal and abnormal ducts. AB - Recent reports have described thickening and enhancement of the extrahepatic bile duct wall on CT scans obtained after administration of IV contrast material. We undertook this study to establish parameters for the normal thickness and enhancement of the bile duct wall on CT, and to develop a differential diagnosis for thickening of the duct wall. Routine CT examinations of 100 patients without biliary disease were evaluated prospectively. The common hepatic duct and common bile duct could be visualized in 66% and 82% of cases, respectively; the walls of these ducts could be separately discerned in 59% and 52%. The mean thickness of the duct wall was 1 mm, with a maximal thickness of 1.5 mm. Wall enhancement was similar to (51%), slightly greater than (44%), or markedly greater than (5%) the enhancement of adjacent pancreatic parenchyma. A review of records covering a 5 year period identified 52 patients in whom CT showed thickening of the bile duct wall (greater than or equal to 2 mm). These patients could be categorized by seven underlying diseases, and analysis of the CT scans revealed four general patterns of thickening. Focal, concentric wall thickening in the distal common bile duct was associated with pancreatitis, pancreatic cancer, and common bile duct stones; focal, eccentric thickening tended to occur with cholangiocarcinoma and sclerosing cholangitis. Diffuse, concentric thickening was seen with acute cholangitis; diffuse, eccentric thickening was associated with oriental cholangiohepatitis and sclerosing cholangitis. Thickening of greater than 5 mm was seen only with cholangiocarcinoma. Enhancement of the duct wall in these groups varied and was of no predictive value. In summary, the extrahepatic bile ducts can be visualized in the majority of patients, and the normal duct wall should be 1.5 mm or less in thickness. Contrast enhancement of the duct wall occurs in patients without biliary tract disease and alone is predictive not predictive of pathology. Pancreatitis, pancreatic cancer, common bile duct stones, cholangiocarcinoma, sclerosing cholangitis, acute cholangitis, and oriental cholangiohepatitis are associated with thickening of the duct wall. PMID- 2104732 TI - Caudate lobe of the liver: anatomy, embryology, and pathology. PMID- 2104733 TI - Gastrointestinal complications of cytosine-arabinoside chemotherapy: findings on plain abdominal radiographs. AB - We analyzed the findings on plain abdominal radiographs in 24 patients who had adverse gastrointestinal reactions after chemotherapy with cytosine-arabinoside (Ara-C) for treatment of acute leukemia or non-Hodgkin lymphoma. Ara-C was given with vincristine, VP 16-213, daunorubicin, amsacrine, adriamycin, or corticosteroids in various combinations and dosages. The abnormalities noted on plain abdominal radiographs included paralytic ileus (73%), cecal distension (38%), pneumatosis intestinalis (27%), thickened loops of small bowel (19%), and pneumoperitoneum (8%). One patient had small-bowel ileus simulating an obstruction. In 23%, death was directly related to gastrointestinal complications. Bowel wall erosions, necrosis, and transmural or submucosal hemorrhage were the main findings at autopsy. This experience suggests that plain abdominal radiographs are useful in the diagnosis of gastrointestinal complications associated with chemotherapy with Ara-C. PMID- 2104734 TI - Diagnosis of bowel infarction: a comparison of plain films and CT scans in 23 cases. AB - We retrospectively reviewed abdominal CT and plain film findings in 23 proved cases of mesenteric infarction to compare the value of the two techniques. Criteria considered specific for infarction on CT were identified in nine (39%) of 23 patients and comprised pneumatosis in seven patients (30%), mesenteric or portal venous gas in three patients (13%), and focally thick-walled bowel in two patients (9%). Criteria considered specific for bowel infarction on plain films were identified in seven (30%) of 23 patients and comprised focally edematous bowel in six patients (26%) and pneumatosis intestinalis in one patient (4%). Only one patient had specific changes on both CT and plain films, but 15 (65%) of the 23 showed specific changes on at least one study. The results indicate that plain films remain an important tool in patients suspected of mesenteric infarction and can provide information that is complementary to CT. Also, as both studies were nonspecific in eight (35%) of our patients, negative or nonspecific findings should not deter further diagnostic or interventional procedures in patients in whom the clinical suspicion of bowel infarction is high. PMID- 2104735 TI - Pressor effect of inhaled ergotamine in orthostatic hypotension. AB - Treatment of orthostatic hypotension due to autonomic failure frequently necessitates use of pressor agents. Because venous pooling contributes significantly to this disorder, the venoconstrictive properties of ergotamine offer theoretical advantages over pure arteriolar pressor agents. However, the low and erratic bioavailability of oral preparations has hindered the use of ergotamine. Accordingly, the efficacy of inhaled ergotamine tartrate (1 puff, 0.36 mg) was compared to placebo in 8 patients with severe autonomic failure. Blood pressure was monitored in the seated position with an automated device. Ergotamine produced significant increases in systolic (29 +/- 5 mm Hg, p less than 0.01 by analysis of variance) and diastolic (13 +/- 1 mm Hg, p less than 0.001) blood pressures compared to placebo (-9 +/- 5 and -2 +/- 3, respectively). Upright blood pressure 2 hours after administration was significantly greater with ergotamine (119 +/- 8/69 +/- 6 mm Hg) vs placebo (82 +/- 7/59 +/- 5 mm Hg, p less than 0.05). Motionless standing time, a measurement of functional capacity, also improved with ergotamine (200 +/- 58 vs 85 +/- 22 seconds). No side effects were noted, but patients with coronary or peripheral artery disease were excluded. Inhaled ergotamine may provide an effective and practical therapy for disabling orthostatic hypotension due to autonomic failure. PMID- 2104736 TI - Effects of nifedipine on the venodilatory response to nitroglycerin. AB - The venodilatory effect of nifedipine 10 mg orally and the venodilatory effect of nitroglycerin 0.8 mg spray after pretreatment with nifedipine were assessed in 15 healthy men aged 22 to 41 years. Compared to placebo, nifedipine caused arteriolar dilation but did not venodilate (control VV[30] 3.67 +/- 0.24 [mean +/ standard error of the mean], after nifedipine VV[30] 3.41 +/- 0.22 cc/100 cc arm). The venodilatory effect of nitroglycerin was not altered by pretreatment with nifedipine. VV[30] increased by 0.72 +/- 0.14 cc/100 cc arm after nitroglycerin in subjects pretreated with placebo compared to 0.70 +/- 0.09 cc/100 cc arm in subjects pretreated with nifedipine. These results suggest that, at a dose of 10 mg, nifedipine does not venodilate and the venodilatory effect of nitroglycerin is not altered by pretreatment with nifedipine. PMID- 2104737 TI - Coexistent double gammopathy, myeloproliferative disorder, and malignant lymphoma. AB - The authors report a patient with coexistent double gammopathy, a Philadelphia chromosome-negative, bcr rearrangement-negative myeloproliferative disease resembling chronic myelocytic leukemia and a malignant lymphoma of B-cell origin. The double gammopathy consisted of IgM (kappa) and IgG (kappa). Peripheral blood, spleen, and marrow lymphocytes had primarily an IgG (kappa) isotype, whereas lymph node lymphocytes had predominantly an IgM (kappa) surface isotype. Increased numbers of marrow lymphocytes stained doubly for both IgM (kappa) and IgG (kappa). The results suggest that doubly isotypic as well as single isotypic lymphocytes contributed to the double gammopathy. Organ localization differed for lymphocytes with different antibody isotypes. This cluster of findings has not been described previously. PMID- 2104738 TI - Lymphocytic lymphoma with associated gamma heavy chain and IgM-lambda paraproteins. An unusual biclonal gammopathy. AB - Evaluation of proteinuria in a 66-year-old white female detected the presence of two distinct anomalous proteins: a gamma heavy chain devoid of light chains and an intact IgM-lambda paraprotein. The gamma heavy chain protein was incomplete, antigenically corresponding to the Fc portion of the molecule. Subsequent diagnostic studies of the patient revealed the simultaneous presence of an adenocarcinoma of the colon and an extranodal well-differentiated lymphocytic lymphoma involving the lungs, pulmonary hilum, and upper gastrointestinal tract. Levels of the two paraproteins were unaltered by surgical excision of the colonic carcinoma but were reduced by chemotherapy directed at the lymphoma. PMID- 2104739 TI - Would another test (anti-HCV) have helped? PMID- 2104740 TI - Hepatitis with isolated serum antibody to hepatitis B core antigen. A variant of non-A, non-B hepatitis? AB - Antibody to hepatitis B core antigen (anti-HBc) has previously been recognized to be a sensitive marker of hepatitis B virus (HBV) infection. In addition, anti-HBc has recently been suggested to be a surrogate marker for non-A, non-B hepatitis agents in donated blood. The authors studied prospectively the HBV antigen and antibody status in four patients with chronic hepatitis and persistent presence of isolated anti-HBc in their sera. The serologic and histopathologic findings of these four patients were compared with those of three groups of patients having chronic hepatitis with or without HBV markers. A low concentration of serum HBV DNA was detected in only one of the four patients with hepatitis with isolated anti-HBc and in another patient with previous HBV infection. HBV antigens and HBV DNA were not detected in the sera and liver biopsies from the remaining patients with hepatitis with isolated anti-HBc and other patients with hepatitis with or without serologic markers of previous hepatitis A or HBV infection. In contrast, all patients with chronic HBV-associated hepatitis had detectable HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) in their sera and/or liver biopsies. These findings suggest that chronic hepatitis associated with isolated anti-HBc is a heterogenous pathologic entity. The condition of some of these patients may represent a variant of non-A, non-B hepatitis, whereas the remaining patients are chronic hepatitis B carriers with low serum concentrations of HBV. PMID- 2104741 TI - Molecular analysis of hemophilia A mutations in the Finnish population. AB - We have examined the Finnish hemophilia A population for factor VIII gene mutations. This study included 83 unrelated patients and revealed 10 mutations associated with hemophilia. Using cloned cDNA, genomic, and oligonucleotide probes, we have identified three classes of mutations: five mutations causing the loss of TaqI restriction sites, a point mutation resulting in a new TaqI site, and four partial gene deletions. Although exons 5 and 6 were involved in three of the four partial gene deletions, the extent of the DNA lost differs in each case. The fourth deletion was located entirely within intron 1 and segregated with the disease in a large hemophilia pedigree. There was no history of hemophilia in eight of the 10 families. The origin of the mutation was determined in six of these pedigrees, two of which showed evidence for maternal mosaicism. PMID- 2104742 TI - Misoprostol in treatment of gastropathy due to nonsteroidal anti-inflammatory drugs. PMID- 2104743 TI - The laboratory diagnosis of lupus anticoagulants. PMID- 2104744 TI - Elevated tumor necrosis factor alpha production concomitant to elevated prostaglandin E2 production by trauma patients' monocytes. AB - The level of tumor necrosis factor alpha (TNF alpha), a monokine implicated in mediating septic shock, is elevated in the blood of some patients with sepsis. Monocytes from 11 trauma patients and 11 burn patients were suboptimally stimulated with interferon gamma and muramyl dipeptide, an analogue of bacterial wall products. The patients with sepsis showed significantly greater total TNF alpha levels (secreted in combination with cell-associated) 3 days before septic episodes, as compared with normal controls (32.38 to 2231.76 ng/10(6) monocytes per milliliter, median = 121.03 ng/10(6) monocytes per milliliter; normal control: 0.00 to 18.20 ng/10(6) monocytes per milliliter, median = 5.93 ng/10(6) monocytes per milliliter). Increases in patients' total monocyte TNF alpha levels greater than 30 ng/10(6) monocytes per milliliter correlated with septic episodes. In patients with sepsis, the total monocyte TNF alpha levels were increased despite a concomitant increase in their prostaglandin E2 levels in both stimulated (interferon gamma plus muramyl dipeptide) and unstimulated in vitro assays (9 patients: stimulated prostaglandin E2 range, 30.1 to 123.6 ng/10(6) monocytes per milliliter). Massively elevated monocyte TNF alpha and prostaglandin E2 production occurred simultaneously in patients with sepsis. PMID- 2104745 TI - Identification of a novel tumor necrosis factor alpha/cachectin from the livers of burned and infected rats. AB - Tumor necrosis factor alpha (TNF-alpha)/cachectin is a monocyte/macrophage derived cytokine implicated as a proximal mediator of many of the catastrophic host responses to infection or endotoxin. However, circulating levels of TNF alpha/cachectin have only been episodically detected in hospitalized patients with life-threatening bacterial infections. In the present report, increased quantities of immune-reactive TNF-alpha/cachectin were recovered from the livers of rats 3 days following a lethal burn and infection. Two species of TNF alpha/cachectin were detected, one of approximately 29 kd and the other 17 kd, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In murine peritoneal macrophages and rat Kupffer cells stimulated in vitro with endotoxin, a 29-kd cell-associated and 17-kd secreted form were also detected. We conclude that the increased appearance in vivo of a 29-kd form of TNF alpha/cachectin from the livers of lethally burned and infected rats represents a novel cell-associated form of the protein. PMID- 2104746 TI - Ruptured arteriovenous malformation complicating thrombolytic therapy with tissue plasminogen activator. AB - It is though that the clot-specific activity of tissue plasminogen activator, used in the treatment of acute myocardial infarction, makes bleeding complications less common than does the use of either streptokinase or urokinase. The incidence of intracerebral hemorrhage complicating the use of tissue plasminogen activator has been estimated to be 0.68%. This is a report of the rupture of an intracranial arteriovenous malformation complicating the use of tissue plasminogen activator therapy. Theories for the mechanism of hemorrhage in this instance are presented, as are suggestions for future use of the enzyme. PMID- 2104747 TI - Epilepsy, myasthenia gravis, and effect of plasmapheresis on antiepileptic drug concentrations. AB - A 28-year-old woman developed complex partial seizures at the age of 17 years and was treated with phenytoin sodium. Five years later she developed myasthenia gravis, and phenytoin was replaced by valproic acid and phenobarbital. She required plasmapheresis (PP). During one course of PP, total and unbound concentrations of valproic acid and phenobarbital were measured in serum sampled before, during, and after PP and in plasma removed by PP. It was determined that the magnitude of loss of valproic acid or phenobarbital by PP was small, and the changes of unbound/total ratio did not reach clinical importance. PMID- 2104748 TI - Intravenous gamma globulin as adjunct therapy for severe group B streptococcal disease in the newborn. AB - Group B streptococcal (GBS) disease remains a significant cause of morbidity and mortality among newborns despite aggressive antibiotic and supportive therapy. Recent success with the prophylactic use of intravenous gamma globulin (IVIg) in newborns suggests that use of IVIg may be an additional therapy for infants with severe GBS disease. Eighty-four infants with GBS antigen in serum, urine, and in some cases spinal fluid were identified by a rapid latex agglutination assay. Twenty-four of these infants had both neutropenia and serum GBS antigen titers of 1:10 or greater and had the highest risk of dying from their infection. Before the availability of IVIg, seven of the first 12 of these infants identified with the highest risk factors died (58%). Twelve additional patients with these highest risk factors have been treated with IVIg. Two of these 12 died (17%), p less than 0.01 when compared with the previous highest risk group. In surviving patients in both IVIg-treated and non-IVIg-treated groups, the time for recovery from neutropenia was 2 to 4 days. Our study suggests a possible beneficial effect of IVIg as adjunct therapy in severe GBS disease. PMID- 2104749 TI - Use of a pediatric parenteral amino acid mixture in a population of extremely low birth weight neonates: frequency and spectrum of direct bilirubinemia. AB - This retrospective study demonstrates a low frequency of parenteral nutrition associated direct bilirubinemia within a population of extremely low birthweight neonates (1000 gm or less) exposed to a pediatric amino acid mixture. PMID- 2104750 TI - [Studies on the Rett syndrome. Part 2. Polysomnographic and neuroendocrinological studies]. AB - The biogenesis of the Rett syndrome (RS) is unknown although there have been several reports suggesting some biochemical defect of the monoaminergic system in CNS. We performed all night polysomnography and neuroendocrinological tests in three cases of RS discovered on a surveillance study in Tokushima. The following results were obtained; 1) dissociation of sleep elements (stage 1-REM, stage 2 REM), 2) no increase in REMs/min with development, 3) abnormal patterns of BMs, TMs of each sleep stage, 4) paradoxical secretion of growth hormone (GH) and excessive secretion of prolactin in TRH provocation test, the absence of sleep enhancement of GH secretion, 5) progressive disfunction of autonomic nervous system during sleep. These results indicated that RS involves the functional disturbances of brain stem and hypothalamic monoaminergic regulatory systems. PMID- 2104751 TI - [A case of atonic partial seizure]. AB - This report presented a 4-year-old girl who had atonic partial seizure of the right leg accompanied by impaired equilibrium. This patient had a generalized tonic-clonic seizures before, and had been on anticonvulsant medication. Mild cataplexy of the right leg and flail trunk while standing occurred abruptly. Based on clinical symptoms, physiological findings, and an electroencephalogram taken at the time of seizure, the cataplexy of the right leg was diagnosed as epileptic seizures. After the dosage of anticonvulsant drug was increased, all symptoms disappeared completely. Cases of atonic partial seizure have been reported only rarely. In our case, atonic partial seizure was associated with nonepileptic equilibrium impairment, probably due to cerebral cortex dysfunction. This is an extremely rare occurrence. PMID- 2104752 TI - [Valproic acid induced pseudohypercreatininemia]. PMID- 2104753 TI - Changes in the activities of amino acid transport systems b0,+ and L during development of preimplantation mouse conceptuses. AB - Uptake of leucine, lysine, and arginine was predominantly Na(+)-independent in mouse conceptuses through the 8-cell stage of development, and two components of saturable transport were detected for each of these amino acids. Uptake of cationic substrates from solutions near 1 microM was inhibited most strongly by bulky cationic and zwitterionic amino acids whose carbon skeletons do not branch at the alpha or beta positions. By this criterion, system b0,+ accounted for most of the Na(+)-independent arginine and lysine transport in eggs and conceptuses throughout preimplantation development. A small, leucine-resistant, cation preferring component of amino acid transport was also detected in these cells. Leucine uptake was inhibited most strongly by bicyclic, branched-chain or benzenoid, zwitterionic amino acids in eggs and conceptuses prior to formation of blastocysts. Therefore, it appeared to be taken up mainly by system L, while system b0,+ accounted for a smaller portion of leucine uptake during this developmental period. In blastocysts, in contrast, system L was less conspicuous, and system b0,+ was primarily responsible for Na(+)-independent leucine uptake. The Vmax values for transport of amino acids by system b0,+ increased by up to 30 fold in conceptuses between the 1-cell and blastocyst stages. In contrast, the Vmax value for leucine transport via system L decreased while the Km value increased between these two developmental stages. Although several explanations for these changes are possible, we favor the hypothesis that the density of system L transport sites in plasma membranes decreases while the number of system b0,+ sites increases during development of blastocysts from 1-cell conceptuses. PMID- 2104754 TI - Fatty acid binding protein (FABP) modulates prostaglandin E binding to rat epididymal adipocyte membrane similarly to albumin. AB - Albumin enhances prostaglandin E2 (PGE2) binding to isolated epididymal adipocyte membrane and also binds PGE2 with low affinity. On the other hand, S-100, ovalbumin and albumin-stearate failed to bind PGE2, as shown by ultrafiltration, and also failed to enhance PGE2 binding to the isolated adipocyte membranes. These results suggested that albumin enhances PGE2 binding possibly by serving as a carrier for the prostaglandin molecules. 3 mM warfarin or 1 mM phenylbutazone inhibited PGE2 binding to albumin by 70% and 95%, respectively, but both drugs failed to affect the enhancement of PGE2 binding to the isolated adipocyte membrane in the presence of albumin. These results exclude the possibility that PGE2 bound to albumin is more accessible to the prostaglandin receptor than free PGE2 in solution. Finally it is shown that fatty acid binding protein (FABP), a cytosolic protein which binds specifically PGE1 but not PGE2, enhances PGE1 and PGE2 binding to isolated adipocyte membranes similarly to albumin. The physiological implications of these findings are discussed. PMID- 2104755 TI - Conformational changes in ornithine decarboxylase enable recognition by antizyme. AB - Rapid, polyamine-induced degradation of mammalian ornithine decarboxylase (L ornithine carboxy-lyase, EC 4.1.1.17) (ODC) is though to be controlled by the availability of a small, ODC-binding protein termed antizyme. In this study we have investigated the ability of antizyme to bind ODC protein in various altered physiological states. In particular, cold, NaCl, spermidine and deprivation of coenzyme and substrate enhance enzyme-antizyme complex formation and are all found to promote ODC homodimer dissociation. Conversely, conditions that maintain the active ODC homodimer state prevent antizyme binding and inactivation of ODC. Further, covalent modification of ODC near its active site by difluoromethylornithine or phosphate also increases its sensitivity to antizyme. These results suggest that the initial signal in ODC degradation may actually be a subtle conformational change in the enzyme that enables antizyme to bind to the enzyme and may subsequently facilitate its degradation. PMID- 2104756 TI - 2-Amino-3-ketobutyrate CoA ligase of Escherichia coli: stoichiometry of pyridoxal phosphate binding and location of the pyridoxyllysine peptide in the primary structure of the enzyme. AB - Pure 2-amino-3-ketobutyrate CoA ligase from Escherichia coli, which catalyzes the cleavage/condensation reaction between 2-amino-3-ketobutyrate (the presumed product of the L-threonine dehydrogenase-catalyzed reaction) and glycine + acetyl CoA, is a dimeric enzyme (Mr = 84,000) that requires pyridoxal 5'-phosphate as coenzyme for catalytic activity. Reduction of the hololigase with tritiated NaBH4 yields an inactive, radioactive enzyme adduct; acid hydrolysis of this adduct allowed for the isolation and identification of epsilon-N-pyridoxyllysine. Quantitative determinations established that 2 mol of pyridoxal 5'-phosphate are bound per mol of dimeric enzyme. After the inactive, tritiated enzyme adduct was digested with trypsin, a single radioactive peptide containing 23 amino acids was isolated and found to have the following primary structure: Val-Asp-Ile-Ile-Thr Gly-Thr-Leu-Gly-Lys*-Ala-Leu-Gly-Gly-Ala-Ser-Gly-Gly -Tyr-Thr-Ala-Ala-Arg (where * = the lysine residue in azomethine linkage with pyridoxal 5'-phosphate). This peptide corresponds to residues 235-257 in the intact protein; 10 residues around the lysine residue have a high level of homology with a segment of the primary structure of 5-aminolevulinate synthase from chicken liver. PMID- 2104757 TI - The sulfhydryl content of L-threonine dehydrogenase from Escherichia coli K-12: relation to catalytic activity and Mn2+ activation. AB - When oxidized to cysteic acid by performic acid or converted to carboxymethylcysteine by alkylation of the reduced enzyme with iodoacetate, a total of six half-cystine residues/subunit are found in L-threonine dehydrogenase (L-threonine: NAD+ oxidoreductase, EC 1.1.1.103; L-threonine + NAD(+)----2-amino 3-oxobutyrate + NADH) from Escherichia coli K-12. Of this total, two exist in disulfide linkage, whereas four are titratable under denaturing conditions by dithiodipyridine, 5,5'-dithiobis(2-nitrobenzoic acid), or p-mercuribenzoate. The kinetics of enzyme inactivation and of modification by the latter two reagents indicate that threonine dehydrogenase has no free thiols that selectively react with bulky compounds. While incubation of the enzyme with a large excess of iodoacetamide causes less than 10% loss of activity, the native dehydrogenase is uniquely reactive with and completely inactivated by iodoacetate. The rate of carboxymethylation by iodoacetate of one -SH group/subunit is identical with the rate of inactivation and the carboxymethylated enzyme is no longer able to bind Mn2+. NADH (0.5 mM) provides 40% protection against this inactivation; 60 to 70% protection is seen in the presence of saturating levels of NADH plus L-threonine. Such results coupled with an analysis of the kinetics of inactivation caused by iodoacetate are interpreted as indicating the inhibitor first forms a reversible complex with a positively charged moiety in or near the microenvironment of a reactive -SH group in the enzyme before irreversible alkylation occurs. Specific alkylation of one -SH group/enzyme subunit apparently causes protein conformational changes that entail a loss of catalytic activity and the ability to bind Mn2+. PMID- 2104758 TI - Meta-iodobenzylguanidine (MIBG), a novel high-affinity substrate for cholera toxin that interferes with cellular mono(ADP-ribosylation). AB - Meta-iodobenzylguanidine (MIBG) is a guanidine analogue of the neurotransmitter norepinephrine. Radioiodinated [131I]MIBG is clinically used as a tumor-targeted radiopharmaceutical in the diagnosis and treatment of adrenergic tumors. Moreover, non-radiolabelled MIBG exerts several cell-biological effects, tentatively ascribed to interference with cellular mono(ADP-ribosyl) transferases (Smets, L.A., Bout, B. and Wisse, J. (1988) Cancer Chemother. Pharmacol. 21, 9 13; Smets, L.A., Metwally, E.A.G., Knol, E. and Martens, M. (1988) Leukemia Res. 12, 737-743). In the present study it was investigated whether MIBG could serve as an acceptor for the ribosyl transferase activity of cholera toxin and of erythrocyte membranes. MIBG appeared a substrate for the cholera toxin-catalyzed transfer of the ADP-ribose moiety of NAD to arginine-like residues with the highest affinity for this enzyme reported as yet (Km = 6.5 microM). MIBG was also ADP-ribosylated by the mono(ADP-ribosyl)transferase(s) of turkey erythrocyte membranes. Moreover, the drug appeared a potent affector of the ADP-ribose linkage to membrane proteins by these enzymes. Interference by MIBG was stronger than by related guanyltyramine, the monoamine precursors of MIBG, meta iodobenzylamine had no effect at all. In contrast, the drug failed to affect endogenous, O-linked poly(ADP-ribose) polymerase, induced in nuclei of S49 leukemia cells by deoxyribonuclease. Since MIBG is the first described drug that specifically interferes with the cellular N-linked mono(ADP-ribosyl) transferase reactions, it may be an important tool to elucidate the physiological role of this posttranscriptional protein modification. PMID- 2104759 TI - Central nervous system effects of lactate infusion in primates. AB - The concentration of total lactate in cisternal fluid increased threefold, from 12.3 +/- 2.1 to 37.6 +/- 8.9 mg/dl, during a 20-min intravenous infusion of 1 M racemic sodium lactate (10 mEq/kg) in 3 anesthetized, mechanically ventilated baboons. Rises in cisternal lactate lagged behind arterial lactate increases, but occurred during the time interval in which susceptible humans typically panic in response to lactate infusion. Subsequent to cisternal lactate increases, cisternal pH and HCO3- concentration progressively increased during a 105-min interval following lactate infusion. No consistent changes in cisternal pCO2 occurred during or subsequent to lactate infusion. These preliminary findings fail to support the hypothesis that lactate-induced panic is mediated by increasing central nervous system pCO2. Instead, these data demonstrate that lactate can rapidly increase in the central nervous system during lactate infusion, suggesting new lines of investigation for studying the mechanisms responsible for lactate-induced panic. PMID- 2104760 TI - Failure of glucose infusion to suppress the exaggerated GH response to GHRH in patients with anorexia nervosa. AB - The growth hormone (GH) response to GH-releasing hormone (GHRH) is characteristically exaggerated in anorexia nervosa (AN). Hyperglycemia suppresses the GH response to GHRH in normal subjects. To test whether this inhibitory action of hyperglycemia is preserved in AN, we performed a GHRH (GHRH 1-40, 1 micrograms/kg) test under basal conditions (saline infusion) and during steady state hyperglycemia (200 mg/dl, induced by the intravenous administration of 8 mg/min.kg of glucose) in 6 adolescent girls with acute-stage AN (as diagnosed by psychopathological, hormonal, and nutritional criteria) and in 5 age-matched female controls. In control subjects, GHRH stimulated GH release during saline, but not glucose, infusion. In the anorectic patients, the GH response to GHRH was exaggerated during both saline infusion (2.97 +/- 0.79 versus 0.52 +/- 0.22 micrograms.120 min.ml-1, p less than 0.02) and under hyperglycemic conditions (4.61 +/- 0.56 versus 0.33 +/- 0.10, p less than 0.001). We conclude that the inhibitory action of hyperglycemia on GHRH-induced GH release is lost in the acute phase of AN. PMID- 2104761 TI - A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction. AB - The patients with inherited bleeding diathesis related to quantitative, structural, and/or functional abnormalities of von Willebrand factor (vWF) are said to have von Willebrand's disease (vWD). We report here the clinical and laboratory features of a 50-year-old woman with a life-long history of excessive bleeding. Her particular laboratory data are factor VIII (FVIII) deficiency, subnormal bleeding time, and the presence of all plasma and platelet vWF multimers in normal amounts. Infused with FVIII/vWF concentrate, she showed a persistent increase in FVIII that led us to discard hemophilia A carrier or "acquired hemophilia" diagnoses. vWF devoid of FVIII purified from normal and patient's plasma by immunoaffinity on anti-vWF monoclonal antibody (MoAb) was immobilized onto polystyrene tubes that were further incubated with purified normal FVIII. The bound FVIII was evidenced using radiolabeled anti-FVIII MoAb. The data showed that the patient's vWF, in contrast to vWF purified from normal plasma, was unable to bind FVIII. Furthermore, no inhibitor of FVIII/vWF interaction was evidenced in incubating purified normal vWF with the patient's plasma before the addition of FVIII and anti-FVIII MoAb. These results support the concept that the bleeding diathesis of this patient appears to be due mainly to her abnormal vWF preventing FVIII/vWF interaction. This abnormality, which is not yet described in present classification of vWD, could be considered as a new variant of vWD. PMID- 2104762 TI - Activation of lymphocytes induced by recombinant human granulocyte-macrophage colony-stimulating factor in patients with malignant lymphoma. AB - To investigate effects of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) on lymphoid cells in vivo, we monitored changes in absolute lymphocyte counts, plasma concentrations of soluble interleukin-2 receptor (sIL-2R) and soluble cytotoxic/suppressor (sCD8) antigens, and phenotypic changes of surface membrane antigens of peripheral mononuclear cells from 14 patients with malignant lymphoma treated with rhGM-CSF. Eight of the 14 patients had relapsed or had refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after intensive chemotherapy with novantrone (NO) and high-dose Ara-C (AC) (NOAC) as salvage regimen. Six other patients with NHL or Hodgkin's disease (HD) were in complete remission and treated with rhGM-CSF to enhance peripheral hematopoietic progenitor cell harvest for autografting. An increase in absolute lymphocyte count at the zenith of leukocyte elevation and a drastic increase in concentration of sIL-2R from a median of 565 U/mL to 6,700 U/mL on rhGM-CSF infusion were found in all patients. There was also a moderate increase in sCD8 levels from a median of 277 U/mL to 470 U/mL. Ten patients were available for serial studies of phenotypic changes in surface membrane antigens. A significant increase in CD25+ (IL-2R+) (P = .0020) and CD4+ (P = .0137) lymphocytes was observed in all patients, but no significant change in CD3+, CD8+, TCR delta 1+, or CD19+ cells. Elevations in absolute lymphocyte counts or in concentrations of sIL-2R or sCD8 were not observed in four other patients during recovery from intensive chemotherapy without rhGM-CSF support. Our results provide evidence that administration of rhGM-CSF might activate lymphocytes in vivo. The impact of this activation on the remission rate and duration, as well as survival in patients with NHL, warrants further investigation. PMID- 2104763 TI - Human umbilical vein endothelial cells secrete transcobalamin II. AB - Transcobalamin II (TC II) is essential for cellular uptake of cobalamin. However, the origin of this transport protein is controversial and many organ sources have been suggested. We studied human umbilical vein endothelial cells cultured in vitro. The cells contained TC II (2.3 pmol/10(8) cells) and released progressively increasing amounts of the protein into the surrounding medium during the 3-day incubation period. This release exceeded the starting intracellular content of TC II. In contrast, endothelial cells did not contain or elaborate R binder, the other major circulating binding protein for cobalamin, Cycloheximide inhibited the elaboration of TC II, suggesting that the endothelial cells synthesize the protein. Thrombin, which stimulates tissue plasminogen activator release, did not enhance TC II release, and neither did endotoxin or mellitin. However, thrombin did appear to partially protect TC II release from inhibition by cycloheximide. Among other cells studied, human fibroblasts also released TC II into the incubation medium, while K562 human leukemia cells, ARH 77 and HS Sultan human plasma cell lines, and Raji strain lymphoblasts did not. The data suggest that endothelial cells are an important source of the metabolically crucial TC II. PMID- 2104764 TI - Enzymatic evidence for differences in the placement of Rh antigens within the red cell membrane. AB - Intact erythrocytes of different Rh genotypes were subjected to various enzyme treatments, the effects of which were monitored by separating the membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and performing Western blotting using an antibody preparation that recognizes only Rh related polypeptides. We found that treatment of intact cells with either phospholipase A2 or proteases such as papain did not alter the size of Rh antigen containing polypeptides. In contrast, phospholipase A2 treatment followed by papain digestion cleaved a fraction of these polypeptides. This cleavage appears, from such digestions of Rh(D) positive and negative cells of different genotypes, to occur solely at the extracellular domain of Rh(D) polypeptide, while the extracellular domains of other Rh antigen-containing polypeptides are unaffected. Digestion of red blood cell ghosts and inside-out vesicles with trypsin showed that Rh(D), (C/c), and (E/e) antigen-containing polypeptides span the lipid bilayer having cytoplasmic domains susceptible to the action of proteases. The size of the cleavage products at the cytoplasmic domain of -D-/-D- cells was found to differ from that of other Rh(D) positive genotypes, due possibly to a difference in folding of Rh(D) polypeptide at its cytoplasmic domain and within the cellular membrane of these cells. PMID- 2104765 TI - Noncoagulation inhibitory factor VIII antibodies after induction of tolerance to factor VIII in hemophilia A patients. AB - We recently described tolerance induction with factor VIII/IX, cyclophosphamide, and high-dose intravenous IgG in hemophilia A or B patients with coagulation inhibitory antibodies. Circulating noninhibitory antibodies complexed with factor IX have been demonstrated in tolerant hemophilia B patients. Similar findings are now described in six tolerant hemophilia A patients. Complexes between factor VIII and the 'tolerant' antibody were demonstrated by subjecting plasma to gel filtration chromatography, void fractions containing factor VIII/vWF complexes being collected and adsorbed to protein A. Using 125I-labeled F(ab')2 fragments against IgG subclass and factor VIII antigen, complexes between an IgG4 antibody and factor VIII were found to adsorb to protein A. After infusion of factor VIII to tolerant patients, all factor VIII circulated in complex with IgG4 antibody. In three of the patients, the 'tolerant' antibodies inhibited an ELISA specific for factor VIII light chain but, unlike the pretolerant antibodies, did not bind radiolabeled factor VIII heavy chain. Although after induction of tolerance the patients still have circulating IgG4 antibodies against factor VIII, the antibodies differ in specificity, lack coagulation inhibitory activity, and do not enhance the rate of elimination of factor VIII. PMID- 2104766 TI - Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A. AB - The molecular defect responsible for moderate and severe hemophilia A has been identified for two unrelated patients with the CRM-positive form of this disorder (factor VIII activity of 0.02 and 0.05 U/mL with factor VIII antigen of 0.87 and 2.20 U/mL). In both cases, the immunopurified dysfunctional factor VIII protein is abnormal, in that the 80 Kd light chain is not cleaved by thrombin at arginine 1689. The basis for this failure was identified by polymerase chain reaction amplification of exon 14 of the variant factor VIII genes and direct sequencing of the amplified products. In both cases, a single base substitution (C to T) was identified that produces an arginine to cysteine substitution at amino acid residue 1689. These data identify the molecular defects of the two identical factor VIII variant proteins. The dysfunctional factor VIII has been designated "Factor VIII-East Hartford," the residence of the patient in whom the defect was first identified. PMID- 2104767 TI - Platelet aggregation in flowing blood at a site of injury to an endothelial cell monolayer: quantitation and real-time imaging with the TAB monoclonal antibody. AB - Epifluorescence videomicroscopy permits real-time imaging of platelet adhesion/aggregation to a defined microinjury of a monolayer of endothelial cells exposed to flowing blood. The fluorescent label is the TAB murine monoclonal antibody directed against human platelet GP IIB, together with a fluorescein conjugated goat F(ab')2 against murine immunoglobulin. The combination assures specificity for platelet membranes, yet leaves platelet function intact. TAB is first added to gently mixed, citrated human blood; the second antibody is added 1 hour after the first, mixing continuing for a second hour. Bovine aortic endothelial cell monolayers (ECMs), grown on rectangular cover glasses precoated with microfibrillar collagen, comprise one wall of a flow chamber mounted on a vertical microscope stage. A loop of 6-0 sterile suture is drawn across the ECM in order to create microinjuries of width 70 +/- 15 microns (mean +/- SD) oriented in a direction transverse to flow. Platelet adhesion/aggregation is virtually absent on intact and confluent regions of the monolayer. On micro injury sites and at shear rates of 60 to 1,080 sec-1, however, computer-enhanced images obtained by means of videomicroscopy show arrival and adherence of single platelets resulting in the formation of platelet aggregates elongated in the flow direction. When the monolayers are pretreated with 1.0 mmol/L lysine acetylsalicylate, the mean aggregate thickness increases (2P less than .05) to 260 +/- 58% (mean +/- SE, N = 6) of control, aggregates are regularly shed downstream, and the surface area of the injury site covered by platelets is augmented (2P less than .05) from 14.8 +/- 3.9% to 49.2 +/- 4.7% (mean +/- SE, N = 6). Donor ingestion of aspirin, on the other hand, leads to an increase (2P less than .01) in percent surface coverage to 42.7 +/- 8.5 without a concomitant increase in mean aggregate thickness. In parallel with the above, outflow levels of serum thromboxane and prostacyclin are measured by radioimmunoassays (RIAs) for thromboxane B2 and 6-Keto-PGF1 alpha, respectively. Thromboxane B2 is increased (2P less than .01) by monolayer pretreatment with lysine acetylsalicylate from 5.08 +/- 1.47 to 9.35 +/- 2.42, but decreased (2P less than .05) after oral aspirin to 1.21 +/- 0.38 ng/mL (mean +/- SE, N = 6). Levels of 6 Keto-PGF1 alpha were reduced (2P less than .05) by monolayer pretreatment from 0.48 +/- 0.046 to 0.36 +/- 0.016 ng/mL. Platelet adhesion/aggregation at a site of injury to an endothelial cell monolayer, therefore, can be imaged in flowing blood in real time using a monoclonal antibody approach.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2104768 TI - A role for intracellular histamine in collagen-induced platelet aggregation. AB - We previously demonstrated that newly formed intracellular histamine mediates platelet aggregation in response to phorbol-12-myristate-13-acetate (PMA). We now report further investigations of the role of histamine during physiological activation of platelets by collagen. Platelets stirred with collagen produced histamine; the rise in histamine precedes the onset of aggregation. The dose response for collagen stimulation of histamine synthesis and platelet aggregation is similar. Inhibitors of histidine decarboxylase (HDC) block both aggregation and histamine synthesis in parallel. Histamine production is not dependent on aggregation; both the intracellular histamine receptor antagonist, N,N-diethyl-2 [4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), and the cyclooxygenase inhibitors, aspirin and indomethacin, inhibit collagen-induced aggregation but not histamine synthesis. DPPE also inhibits collagen-induced serotonin secretion and thromboxane production. The effects of DPPE and HDC inhibitors are significantly reversed by the addition of histamine (0.1 to 10 mumol/L) to saponin-permeabilized platelets, though histamine alone has no pro-aggregatory effects. The results suggest that newly synthesized intracellular histamine has a role in collagen-induced platelet activation and that it may act to promote the generation of thromboxane and the secretion responses of platelet granules. PMID- 2104769 TI - Evaluation of glucose tolerance, insulin secretion, and insulin action in patients with primary hyperparathyroidism before and after surgery. AB - Glucose tolerance, insulin secretion, and insulin sensitivity were evaluated in 8 asymptomatic patients with primary hyperparathyroidism (PHPT) before and at least 8 weeks after surgical correction of PHPT by means of the hyperglycemic clamp technique. In addition, 15 sex- and age-matched control subjects were investigated for comparative reasons by the same technique. Glucose metabolized (M) during the hyperglycemic clamp was not significantly (NS) different between patients with PHPT and controls (7.9 +/- 2.3 vs. 6.3 +/- 1.9 mg/kg/min). However, insulin secretion (I) was significantly elevated in patients with PHPT compared to controls (87 +/- 17 vs. 45 +/- 12 microU/ml, P less than 0.05). The calculated insulin sensitivity index (M/I) was significantly reduced in PHPT compared to controls (11.0 +/- 2.1 vs. 15.2 +/- 1.4 mg/kg/min per microU/ml x 100, P less than 0.05). Comparing patients with PHPT before and after surgery, the M value, which is a measure of glucose tolerance, was not significantly different (7.9 +/- 2.3 vs. 7.8 +/- 1.5 mg/kg/min). However, insulin secretion was significantly lower after surgical correction of PHPT compared to the preoperative situation (48 +/- 9 microU/ml vs. 87 +/- 17 microU/7 ml, P less than 0.01). The calculated M/I rose significantly after surgery compared to the preoperative value (11 +/- 2.1 vs. 17.6 +/- 2.7 mg/kg/min per microU/ml x 100, P less than 0.001). We conclude that disturbed carbohydrate metabolism, such as insulin hypersecretion and insulin resistance, in patients with PHPT is an early finding in this disease and that these early disturbances in glucose metabolism are, however, fully reversible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104770 TI - Buserelin-mediated osteoporosis: effects of restoring estrogen on bone resorption and whole body calcium content in the rat. AB - In the rat, prolonged administration of the luteinizing, hormone-releasing hormone agonist buserelin (25 micrograms/kg body wt/day s.c.) lowers blood estradiol, raises bone resorption, and induces osteopenia. The present study was undertaken to determine whether withdrawal of buserelin normalizes blood estradiol, slows bone resorption, and corrects buserelin-mediated osteopenia. Four groups of female rats with 45Ca-labeled bones were studied: group 1A received 0.2 ml saline s.c. daily for 4 weeks; group 2A received 0.2 ml buserelin s.c. daily for 4 weeks; group 1B received 0.2 ml saline s.c. daily for 8 weeks; group 2B received 0.2 ml buserelin s.c. daily for 4 weeks followed by 0.2 ml saline s.c. daily for 4 weeks. Bone resorption was monitored by measuring urinary 45Ca and hydroxyproline. The rats in groups 1A and 2A were killed after 4 weeks and those in groups 1B and 2B after 8 weeks. The mineral contents of the femoral bones and the whole skeletons were measured. Buserelin lowered blood estradiol, elevated urinary 45Ca and urinary hydroxyproline, and lowered femur and total body calcium and 45Ca in group 2A vs. 1A (P less than 0.05). By contrast all these measurements became similar in groups 2B and 1B. Thus, osteopenia generated by a 4-week period of buserelin-mediated hypo-estrogenism is reversible by withdrawing buserelin for 4 weeks. Consequently, buserelin administration and withdrawal may be used to study effects of inducing and reversing estrogen deficiency bone loss in the rat. PMID- 2104771 TI - The effect of high-dose salmon calcitonin on bone mineral metabolism in the normal rat. AB - The paucity of information on the effect of long-term high-dose salmon calcitonin administration on normal bone mineral metabolism and histology prompted an investigation of the influence of high-dose synthetic calcitonin in the rat. Serum ionized calcium, osteocalcin or BGP (bone gla protein), and immunoreactive PTH were measured serially during calcitonin administration and bone histomorphometry analyzed at 6 weeks (after sacrifice). Daily injections of salmon calcitonin, 0.4 IU/100 g (group B) and 2 IU/100 g (group C), resulted in significant hypocalcemia at 4 hours for both experimental groups (P less than 0.004). Serum iPTH was significantly higher over the study period for both groups administered calcitonin. Serum BGP levels were significantly lower than controls during the study in group C (P less than 0.002) and to a lesser extent in group B (P less than 0.05). In group C, bone histomorphometry revealed increased resorption (osteoclast count), decreased trabecular bone volume, and decreased double-labeled tetracycline surface (bone formation). In group B an increase in osteoclast count but no alteration in bone formation was observed. To assess the role of PTH in the above findings, high-dose calcitonin was administered to parathyroidectomized rats. All of the above changes in bone histomorphometry were not observed in this group of animals. In conclusion, high doses of calcitonin promote hypocalcemia, secondary hyperparathyroidism, and osteoclastosis in the normal rat in a dose-dependent manner with very high-dose calcitonin impairing bone formation. PMID- 2104772 TI - A light and scanning electron microscopic study of osteocyte activity in calcium deficient rats. AB - The material herein is an extension of an earlier study of osteocyte lacunae in calcium-deficient rats, utilizing morphometric measurements in undecalcified bone sections and scanning electron microscopy. The results confirm our earlier finding that bone resorption resulting from a low-calcium diet is not accompanied by osteocytic resorption. PMID- 2104773 TI - Influence of whole body irradiation and local shielding on matrix-induced endochondral bone differentiation. AB - Subcutaneous implantation of demineralized bone matrix into allogeneic rats induces endochondral bone formation. We have investigated the effects of irradiation on the sequelae of the interaction of collagenous matrix and mesenchymal cells and on cartilage and bone differentiation. Rats were irradiated in a vertical direction with a midline dose of 850 rad. Radiation entered the rats ventrally while a small area of the upper thorax was locally shielded. After irradiation, bone matrix was implanted in shielded and nonshielded sites, and the implants were studied at various stages. On day 3, [3H]thymidine incorporation, an index of cell proliferation, was inhibited by 70% in the nonshielded sites compared to nonirradiated control rats. The degree of inhibition (35%) was less pronounced in shielded sites. Furthermore, there was recovery of cell proliferation in the shielded sites as opposed to the nonshielded contralateral site. A similar pattern was observed on day 7 as assessed by 35SO4 incorporation into proteoglycans during chondrogenesis. Bone formation and mineralization were quantified on day 11 by alkaline phosphatase activity and 45Ca incorporation. In nonshielded sites, there was a 73% inhibition of alkaline phosphatase activity. In conclusion, radiation impaired progenitor cell proliferation which resulted in decreased cartilage and bone differentiation. These findings imply that local mesenchymal cells proliferate and differentiate into bone in response to implanted collagenous matrix. PMID- 2104774 TI - Lipids in bone: optimal conditions for tissue storage prior to lipid analyses. AB - Optimal conditions for storage of calcified tissues prior to lipid analysis were determined by comparing the lipid composition (total lipid, total phospholipid, triglyceride, free fatty acid, cholesterol, and complexed acidic phospholipid) of mature rabbit diaphyseal bone stored 1, 2, and 5 months after animal sacrifice to that observed in the bones from which the lipids were immediately extracted at the time of sacrifice. Storage of lyophilized or nonlyophilized tissues at -70 degrees, or lyophilized tissues at -20 degrees, were the only methods that did not yield significant changes in bone lipid composition with time. PMID- 2104775 TI - Involvement of low-calcium diet in the reduced bone mineral content of idiopathic renal stone formers. AB - The possibility that low-calcium intake in renal stone formers could lead to reduced bone mineral content was investigated in 123 male patients with idiopathic urolithiasis. Radius bone mineral content (BMC) was measured by single photon absorptiometry. Two groups of patients were analyzed: group 1 (n = 63) maintained on a free diet; group 2 (n = 60) maintained on a low-calcium diet (350 mg/day +/- 20 SEM) for 3.9 years +/- 0.6 SEM. The two groups of patients were investigated after a standard reduction of calcium intake for at least 1 week. The urinary excretion of calcium and of hydroxyproline, and the serum alkaline phosphatase activity were higher in both groups than in normal subjects submitted to the same low-calcium diet. Both groups of stone formers showed lowered radius BMC values at 3 cm (distal) and 8 cm (proximal) above the styloid process, but distal BMC was significantly lower in group 2 than in group 1. The results suggest that low-calcium intake could worsen the already decreased BMC of idiopathic renal stone formers. PMID- 2104776 TI - Evaluation of methods for quantitation of aflatoxin-albumin adducts and their application to human exposure assessment. AB - Aflatoxin (AF) albumin adducts are found in peripheral blood after exposure to aflatoxin B1 (AFB1) and the measurement of these adducts is potentially a useful tool in the epidemiological study of the role of AFB1 in the etiology of liver cancer. Three complementary approaches to the quantitation of AF-albumin adducts are described: (a) enzyme-linked immunosorbent assay (ELISA) performed directly on intact albumin (direct ELISA); (b) ELISA performed on an albumin hydrolysate (hydrolysis ELISA); (c) high-performance liquid chromatographic fluorescence detection of AF-lysine adduct after albumin hydrolysis and immunoaffinity purification. These techniques have been validated by direct comparison with rat albumin samples modified to a known extent. Detection limits of approximately 100, 5.0, and 5.0 pg AF/mg human albumin were determined for the three methods, respectively. Samples obtained from individuals from Thailand, The Gambia, Kenya, and France have been used to validate the measurement of AF-albumin adducts by these three methods. Levels of 7 to 338 pg AF/mg albumin were observed in the former two countries while no adducts were detected in samples from France. The relative properties of the three assays, with special regard to their application in epidemiological studies, are considered. A combination of the hydrolysis ELISA for large scale screening followed by confirmatory analyses in positive samples by high-performance liquid chromatographic fluorescence is suggested as an optimum methodology. PMID- 2104777 TI - How does the nose know? PMID- 2104778 TI - Purification and characterization of an 85 kDa talin-binding fragment of vinculin. AB - Vinculin and talin are adhesion plaque proteins which have been shown to interact with each other in vitro. In order to begin to investigate where the talin binding domain is in vinculin, vinculin was digested with Staphylococcus aureus V8 protease to generate two major fragments of 85 and 30 kDa, and these fragments were purified. Nitrocellulose overlays with 125I-talin and the 125I-85 kDa vinculin fragment and sucrose density gradient centrifugation demonstrated that the talin-binding domain was localized to the 85 kDa vinculin fragment. Quantification of 125I-talin binding in the overlays showed that four times more talin bound to the 85 kDa fragment as compared to intact vinculin. Competitive immunoprecipitation experiments demonstrated that unlabeled 85 kDa fragment was about three-fold more effective at competing for 125I-85 kDa binding to talin than was unlabeled vinculin. These results suggest that the 30 kDa fragment inhibits the vinculin-talin interaction even though the talin-binding domain is localized in the 85 kDa fragment. PMID- 2104779 TI - Unconjugated pteridines and the activation of macrophages by interferon gamma. PMID- 2104780 TI - Expression of the poly(ADP-ribose) polymerase gene following natural and induced DNA strand breakage and effect of hyperexpression on DNA repair. AB - The catalytic activity of the nuclear enzyme poly(ADP-ribose) polymerase (NAD+ ADP-ribosyl transferase, EC 2,4,2,30) is totally dependent upon the presence of DNA strand breaks. Having isolated a full-length cDNA for the polymerase, we have now evaluated the effect of endogenously and exogenously induced DNA strand breaks on the transcriptional control of this enzyme. During retinoic acid or dimethyl-sulfoxide-induced differentiation of HL-60 human leukemia cells, which may involve DNA breaks as well as other changes in chromatin, mRNA levels for the polymerase increased very early and remained high for up to 48 h after which it decreased to pre-induced levels. Polymerase transcript levels did not change, however, during the induction of DNA strand breaks by dimethylsulfate, a variety of other alkylating agents, X-irradiation, or UV-irradiation in several mammalian cell lines. It appears that in sharp contrast to the catalytic requirement of the polymerase, the induction of transcription of the polymerase gene may not be a strand-break-dependent process. The noninducibility of the polymerase gene following DNA damage suggested that there may be adequate levels of the polymerase in the cells to cope with DNA damage. To test this hypothesis we examined the efficacy of DNA repair in Cos cells engineered to overexpress the polymerase. Although there was a slight augmentation of the repair rate, this increase was apparent only after very high levels of DNA damage and only at early repair times. After a longer repair period, the extent of repair in control cell was similar to that in the cell overexpressing the polymerase. We thus conclude that the basal levels of the polymerase are adequate for significant amounts of DNA damage. PMID- 2104781 TI - Modulation of the co-promoting activity of gamma interferon in SENCAR and C57BL/6 mouse skin by difluoromethylornithine and the scheduling and duration of interferon treatment. AB - The murine skin multistage carcinogenesis model was used to characterize the co promoting and tumor progressing activities of i.p. administered recombinant DNA derived murine gamma interferon (rMuIFN-gamma). The dorsal skins of female SENCAR mice were topically initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted twice a week for 20 weeks with 1 microgram of 12-O-tetradecanoylphorbol 13-acetate (TPA). Doses of rMuIFN-gamma that had no effect on papilloma multiplicities when administered 1 day prior to TPA treatment increased the numbers of papillomas per mouse by 33-38% when administered immediately prior (zero time) to TPA application. A minimum of 6 weeks of co-treatment with TPA and rMuIFN-gamma (zero time) were necessary for demonstration of rMuIFN-gamma dependent co-promotion. The ad libitum administration of either 0.25 or 1% (w/v) solutions of alpha-difluoromethylornithine (DFMO) in the drinking water inhibited by 90% the TPA-dependent elevation of epidermal ornithine decarboxylase activity but had minimal effect on papilloma multiplicities in TPA-promoted mice. However, both doses of DFMO completely suppressed rMuIFN-gamma-dependent co-promotion. Carcinoma incidence and multiplicities by weeks 46-48 of the promotion progression period were statistically indistinguishable for initiated mice treated with TPA, TPA + DFMO, TPA + IFN-gamma or TPA + DFMO + IFN-gamma. Similarly, i.p. administration of rMuIFN-gamma to papilloma-bearing mice in a tumor progression study, with and without simultaneous topical TPA treatment, did not affect carcinoma latency or carcinoma multiplicities. C57BL/6 mice initiated with DMBA developed few papillomas (0.2 paps/mouse) after 19 weeks of TPA promotion. The i.p. administration of rMuIFN-gamma to C57BL/6 mice at the time of TPA treatment, at doses that were co-promoting in SENCAR mice, did not increase papilloma multiplicities. Collectively, our studies suggest that the co-promoting activity of rMuIFN-gamma is exceptionally sensitive to inhibition by DFMO and dependent upon the scheduling and duration of rMuIFN-gamma treatment, and the mouse strain/stock employed for the studies. PMID- 2104782 TI - High-resolution TLC mapping and characterization of 32P-postlabeled monophosphate 7,12-dimethylbenz[a]anthracene-DNA adducts. AB - Previous work has shown that 7,12-dimethylbenz[a]anthracene (DMBA)-DNA adducts can be converted by 32P-postlabeling to different types of radiolabeled derivatives (nucleoside 3',5'-bisphosphates, nucleoside 5'-monophosphates and dinucleotides), and that the 32P-labeled 3',5'-bisphosphate derivatives can be further characterized by cross-referencing with 3H-labeled nucleoside DMBA adducts, for which structural information is available. This work has now been extended by TLC comparisons of 5'-monophosphate and 3',5'-bisphosphate DMBA adducts. To this end, DMBA-modified DNA was enzymatically hydrolyzed to 3' monophosphates (Xp + Np) or to dinucleotides (XpN), and these digestion products were 32P-postlabeled by published procedures to yield 3',5'-bisphosphate (*pXp) or 5'-monophosphate (*pX) adducts. Individual *pXp and *pX fractions were isolated from polyethyleneimine (PEI)-cellulose TLC maps and chromatographically compared after enzymatic 3'-dephosphorylations of the 3',5'-bisphosphate (*pXp) derivatives (*pXp----*pX + Pi). Four reactions were standardized and employed for this purpose: (i) 3'-dephosphorylation by extensive digestion with nuclease P1; (ii) 3'-dephosphorylation catalyzed by polynucleotide kinase; (iii) partial dephosphorylation by bacterial alkaline phosphatase; and (iv) partial dephosphorylation by prostatic acid phosphatase. Individual DMBA adducts displayed marked differences with regard to their susceptibility to enzymatic dephosphorylation. The three major and most minor postlabeled 5'-monophosphate DMBA adducts were cross-referenced this way with 3',5'-bisphosphate and nucleoside adducts, so that specific dihydrodiol epoxide-nucleoside 5' monophosphate adducts can now be identified and measured by 32P-postlabeling. PMID- 2104783 TI - Aflatoxin-DNA adduct formation in chronically dosed rats fed a choline-deficient diet. AB - Nutritional modulation of male Fischer rats by a choline-deficient/methionine-low diet dramatically increases hepatocarcinogenesis and reduces time to first tumors induced by aflatoxin B1 (AFB1). The effect of this diet on hepatic aflatoxin-DNA adduct burden in male Fischer rats dosed with a carcinogenic regimen of AFB1 was examined in this study. After 3 weeks of ingestion of a choline deficient/methionine-low diet or control semi-purified diet, rats were administered a carcinogenic regimen of 25 micrograms [3H]AFB1 for 5 days a week over 2 weeks. Six choline-deficient and four control diet rats were killed 2 h after each dose, and liver DNA isolated. In addition, hepatic DNA was isolated from animals 1, 2, 3, and 11 days after the last [3H]AFB1 administration. At all time points HPLC analysis of aflatoxin-DNA adducts was performed to confirm radiometric determinations of DNA binding levels. No significant quantitative differences in AFB1-DNA adduct formation between the dietary groups were observed following the first exposure to [3H]AFB1; however, total aflatoxin-DNA adduct levels in the choline-deficient animals were significantly increased during the multiple dose schedule. When total aflatoxin-DNA adduct levels were integrated over the 10 day dose period, a 41% increase in adduct burden was determined for the choline-deficient animals. While this increase in DNA damage is consistent with the hypothesis that DNA damage is related to tumor outcome, the biochemical basis for this effect still needs to be elucidated. PMID- 2104784 TI - Rapid and reversible inhibition by low density lipoprotein of the endothelium dependent relaxation to hemostatic substances in porcine coronary arteries. Heat and acid labile factors in low density lipoprotein mediate the inhibition. AB - The effects of hemostatic substances on the vascular tone in porcine coronary arteries and the influence of low density lipoprotein on tension were investigated. Thrombin induced a marked concentration-dependent relaxation in prostaglandin F2 alpha-precontracted strips with intact endothelium, whereas it produced a modest constriction in endothelium-denuded arteries. Methylene blue abolished the relaxation, but indomethacin did not affect it significantly. An exposure of the intact strips to low density lipoprotein resulted in a marked inhibition of the relaxation to thrombin but did not interfere with vasodilation by sodium nitroprusside. The inhibition by low density lipoprotein was reversed completely by washing. In contrast, high density lipoprotein lacked such inhibitory effects. Adenosine diphosphate, calcium ionophore A23187, and platelet activating factor also produced relaxation in the intact strips. An exposure of the strips to low density lipoprotein almost abolished relaxation to these substances. The inhibition was also reversible. Heat treatment or acid treatment of low density lipoprotein resulted in a complete loss of the inhibitory effects, but diisopropyl fluorophosphate treatment did not alter the effect. It is concluded that low density lipoprotein may play a new pathological role in promotion of coronary vasospasm through rapid and reversible inhibition in endothelium-dependent relaxation to hemostatic substances. PMID- 2104785 TI - A role for a new vascular enzyme in the metabolism of xenobiotic amines. AB - Although it has long been thought that environmental toxins may play an underlying role in vascular diseases such as atherosclerosis, this concept is not supported by any clear-cut experimental evidence of toxic metabolism by cardiovascular enzymes. In this study, we demonstrate that allylamine, a selective cardiovascular toxin in vivo, is actively metabolized in vitro by a purified vascular enzyme (semicarbazide-sensitive amine oxidase), which has been localized recently to vascular smooth muscle cells. Oxidative deamination of allylamine to a highly toxic aldehyde, acrolein, was blocked through enzyme inhibition by semicarbazide-sensitive amine oxidase suggests that this vascular enzyme's physiological role may include metabolism of exogenous amines. PMID- 2104786 TI - Polymorphonuclear leukocytes induced vasoconstriction in isolated canine coronary arteries. AB - To assess how polymorphonuclear leukocytes (PMNs) act on coronary vasoactivity, we measured the changes in isometric tension of isolated rings of canine coronary arteries upon addition of autologous PMNs to organ chambers in which the rings were suspended. When PMNs isolated by the colloidal polyvinylpyrrolidone-coated silica (Percoll) gradient method were added to the chambers, ring preparations of left circumflex coronary arteries developed isometric tension. The increase in tension was dependent on the amount of PMNs (1 X 10(4) to 5 X 10(6) cells/ml). Maximal tension obtained by an optimal amount of PMNs (5 X 10(5) cells/ml) was almost comparable to that produced by prostaglandin F2 alpha (5 microM). Integrity of endothelial cells was not disrupted after the addition of PMNs because the developed tension could be reversed by the addition of acetylcholine in an endothelium-dependent manner. Mechanical rubbing of endothelium abolished the PMN-induced vasoconstriction, which was regained by placing an endothelium unrubbed ring inside a rubbed ring ("sandwich preparation"). When PMN suspensions were pretreated with 5-lipoxygenase inhibitors of arachidonate, PMN-induced vasoconstriction was greatly suppressed, although the pretreatment of vascular preparations did not alter the development of isometric tension. These findings indicate that PMNs induce the contraction of coronary arterial rings in the presence of intact endothelial cells. The mechanism by which PMNs induce the contraction is the release of vasoconstrictive substances by metabolic interaction between PMNs and endothelial cells. Vasoconstrictive substances produced by the PMN-endothelial system, such as 5-lipoxygenase metabolites through a "leukotriene A4 steal" mechanism, may contribute to the contraction of vascular smooth muscle. PMID- 2104787 TI - Peripheral blood monocytes derived from HIV+ individuals mediate antibody dependent cellular cytotoxicity (ADCC). AB - Monocytes/macrophages serve a number of immunologic functions and play a major role in the host defense against infection. Abnormal functions of monocytes have been reported in AIDS and HIV+ individuals. A recent report from our laboratory demonstrated that peripheral blood monocytes (PBM) derived from AIDS patients were de novo "activated" as assessed by direct cell-mediated cytotoxicity (CMC) and secretion of cytotoxic factors and tumor necrosis factor-alpha (TNF alpha). Thus, both the direct cytotoxicity as well as the antibody-dependent cellular cytotoxicity (ADCC) exerted by the monocytes may contribute to the destruction of HIV-infected/coated cells and the immunopathogenesis of AIDS. The present study investigated the ability of HIV+ PBM to mediate ADCC against antibody-coated target cells in an 18-hr 51Cr release assay. Initial studies examined ADCC using a macrophage resistant target Raji and rabbit anti-Raji serum. The results show that the majority of PBM from HIV+ individuals mediate ADCC activity while the majority of PBM from normal healthy controls was not cytotoxic. While activation of PBM with recombinant interferon-gamma (rIFN-gamma) enhances the ADCC activity of normal PBM, treatment of HIV+ PBM with IFN-gamma resulted in significant enhancement of ADCC. Both untreated and treated PBM from HIV+ individuals had significantly higher ADCC than PBM from normal individuals. Of interest, a significant ADCC activity was found by PBM derived from two HIV- high risk individuals whether untreated or treated with rIFN-gamma. The ADCC results with RAJI target cells prompted us to investigate whether ADCC can also be obtained using HIV-infected T4+ cells. We selected a macrophage and TNF resistant T4+ CEM cell line as target for ADCC. The target was coated with inactivated HIV and pooled human anti-HIV serum was used. Studies with a few HIV+ individuals demonstrate that significant ADCC is obtained with PBM from HIV+ individuals but little or no ADCC by normal PBM and the ADCC was specific for HIV. The ADCC was also significantly enhanced by treatment of PBM with rIFN-gamma. The results of this study clearly indicate that PBM from HIV+ individuals are endowed with the capacity to mediate ADCC against HIV-infected/coated cells and thus, we postulate that PBM may play a direct role in vivo in lysis or suppression of HIV coated/infected cells and in the pathogenesis of AIDS. PMID- 2104788 TI - Expression of autoantibodies to recombinant (U1) RNP-associated 70K antigen in systemic lupus erythematosus. AB - To determine the specificity of antibodies to the (U1) ribonucleoprotein antigen in systemic lupus erythematosus (SLE), patient sera were tested for binding to a recombinant human 70K antigen. By solid-phase immunoassay, we detected anti-70K reactivity in sera from 31 of 96 patients with systemic lupus erythematosus (SLE), demonstrating that anti-70K antibodies may occur in patients with SLE as well as other clinical diagnoses. In sequential sera from 2 of these patients, we found that anti-70K binding varied dramatically over the course of disease. The changes in anti-70K antibody levels did not correlate with clinical events nor evolving antibody reactivity with the Sm-specific antigens. PMID- 2104789 TI - IgG1 and IgG2 are the predominant subclasses of antiphospholipid antibody in women with the lupus anticoagulant. AB - We studied the sera of 36 patients with lupus anticoagulant and IgG antibodies against both phosphatidylserine and cardiolipin. Most sera also had IgG antibodies against other phospholipids: 97% against phosphatidylinositol, 91% against phosphatidylglycerol, and 82% against phosphatidylethanolamine. IgG2 was the predominant subclass against cardiolipin and phosphatidylserine; 35 of 36 patients (98%) had IgG2 against both phospholipids. Most patients also had the IgG1 subclass; 32 of 36 (89%) against cardiolipin and 25 of 36 (69%) against phosphatidylserine. IgG3 and IgG4 subclasses were present at very low concentrations and in only a minority of the sera. The antibody response against phosphatidylserine was characterized by significantly less IgG1 than was the response against cardiolipin (P less than 0.01), although the IgG2 responses against each phospholipid were not different. IgG subclasses were unrelated to any other aspect of the patients' history, including a history of thrombocytopenia or thrombosis, a positive antinuclear antibody test, or a diagnosis of systemic lupus erythematosus. PMID- 2104790 TI - Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole. AB - The effect of omeprazole treatment on diazepam plasma levels was studied in four slow and six rapid metabolizers of omeprazole. Single intravenous doses of diazepam (0.1 mg/kg) were administered after 1 week of oral treatment with omeprazole (20 mg) and placebo. This was a double-blind crossover study with randomized placebo and omeprazole treatments. Blood was collected up to 120 hours after diazepam dosing (still during one-daily omeprazole and placebo administration) for measurement of diazepam and its major metabolite desmethyldiazepam. The slow metabolizers of omeprazole also metabolized diazepam slowly, exhibiting only half the diazepam plasma clearance of the others. The mean clearance of diazepam was decreased 26% after omeprazole in the rapid metabolizers, whereas the slow group showed no apparent interaction. The mean plasma concentrations of desmethyldiazepam showed a more rapid formation in the rapid compared with the slow metabolizers, which is a logical consequence of the rate of diazepam metabolism. PMID- 2104791 TI - Stability of patient preferences regarding life-sustaining treatments. AB - Physicians often express concern about the reliability of critically ill patients' preferences regarding life-sustaining treatments. We interviewed 30 Veterans Administration intensive care unit patients to determine their preferences for resuscitation, resuscitation requiring mechanical ventilation, artificial hydration and nutrition, and hospitalization for treatment of pneumonia. Patients expressed their preferences considering their current health and then two hypothetical scenarios, stroke and dementia. Follow-up interviews occurred one month later to assess preference stability. We found a diversity of opinions about life-sustaining treatments. Despite significant changes in health status and mood (p less than 0.05), treatment preferences were stable over time (kappa = .35-.70). Our results suggest that life-sustaining treatment preferences solicited during a serious illness are reliable and may be used in decision making when a patient becomes unable to communicate or is mentally incapacitated. PMID- 2104792 TI - Duration of protective effect of terbutaline sulfate and cromolyn sodium alone and in combination on exercise-induced asthma. AB - For subjects with EIA participating in physical activities throughout the day, prolonged duration of protection is desirable. The purpose of this study was to determine whether in EIA a combination of the recommended aerosol doses of the beta 2-adrenergic receptor agonist, terbutaline sulfate (0.5 mg), and cromolyn sodium (disodium cromoglycate; 2 mg) provides longer protection against EIA than either drug alone. On four separate days, following the administration of either placebo, terbutaline alone, cromolyn sodium alone or terbutaline and cromolyn sodium together, 12 subjects (seven men and five women; aged 18 to 28 years) with EIA performed four identical eight minute treadmill runs, each separated by two hour intervals. Drug treatments were given double-blind, with the order counterbalanced using a Latin-square design. Pulmonary function was recorded before the drug, immediately before and after exercise, and at 3, 4, 5, 6, 7, 10, 15, and 30 minutes after exercise. Inspired ventilation, heart rate, and environmental conditions were monitored during exercise. A two-way analysis of variance was performed to investigate the main effects of time and drug treatment. Results indicated that in comparison with placebo, EIA was significantly reduced by either cromolyn sodium or terbutaline administered up to two hours (p less than 0.01) and by the combination (cromolyn sodium and terbutaline) up to four hours after inhalation (p less than 0.05). No significant differences were found between the combination and terbutaline during the initial two hours (p less than 0.5). We conclude that a combination of beta 2-adrenergic receptor agonist and cromolyn sodium is the treatment of choice for prolonged effective protection from EIA. PMID- 2104793 TI - Management of chronic alveolar hypoventilation by nasal ventilation. AB - This is a study of the effect of nocturnal nasal intermittent positive pressure ventilation (NIPPV) on symptoms of chronic alveolar hypoventilation (CAH), sleep oxygen saturation (SaO2), and frequency of hospitalization of patients with progressive neuromuscular respiratory insufficiency or restrictive lung disease from thoracic wall deformity. The nocturnal use of NIPPV is explored in combination with other noninvasive methods of supported ventilation for daytime support as alternatives to tracheostomy and long-term tracheostomy intermittent positive pressure ventilation (TIPPV). Sixteen patients with less than 400 ml of vital capacity (VC) supine and less than 15 minutes of autonomous respiration (free time) maintained a mean SaO2 of 95.9 +/- 2.6 percent (SD) during sleep on NIPPV without added oxygen. Seventeen other patients with adequate free time for a sleep trial unaided had an average SaO2 of 81.8 +/- 11.0 percent which improved to 94.1 +/- 3.4 percent on NIPPV alone. The average length of use of NIPPV by the 42 patients who have used it for one month or more is 21 (3-67) months. All 34 patients who were not dependent on ventilatory support 24 hours a day demonstrated significant improvement and in most cases normalization of ABG when off aid. Thirteen patients were converted from IPPV via an endotracheal tube or TIPPV to NIPPV. Long-term use of a custom molded thermoplastic nasal interface for the delivery of NIPPV is reported for 17 patients. Unnecessary morbidity and hospitalizations can be avoided by early awareness and appropriate management of CAH. NIPPV can be an effective alternative to TIPPV, body ventilators, or oxygen therapy. PMID- 2104794 TI - Long-term follow-up of nocturnal ventilatory assistance in patients with respiratory failure due to Duchenne-type muscular dystrophy. AB - We followed eight patients with Duchenne-type muscular dystrophy for an average of 39 months after initiation of noninvasive intermittent ventilatory assistance using body ventilators. After one to three months of nocturnal use averaging 8 h, mean daytime PaCO2 fell from 63 +/- 2 to 45 +/- 3 mm Hg. At late follow-up, PaCO2 remained stable at 47 +/- 4 mm Hg, but vital capacity fell 33 percent compared with the initial value and the average duration of ventilator use had increased to 18 +/- 2 h daily. Three patients died and five survived; two continued using negative pressure ventilators and three had tracheostomies placed for administration of positive pressure ventilation. We conclude that noninvasive intermittent ventilatory assistance effectively reverses hypoventilation and symptoms in patients with late-stage Duchenne muscular dystrophy, but pulmonary function continues to deteriorate necessitating longer periods of ventilation, and often tracheostomy, within a few years. PMID- 2104795 TI - Current preoperative bowel cleansing methods. Results of a survey. AB - A mail survey of 300 members of The American Society of Colon and Rectal Surgeons (ASCRS) was conducted to document the current methods of bowel preparation in use. Two hundred six questionnaires (69 percent) were returned. The majority of respondents (104 or 51 percent) used cathartics and enemas as the primary method of mechanical bowel cleansing. Eighty-nine (43 percent) used a PEG lavage, eight (4 percent) used mannitol, and one physician used a saline lavage method. Almost all the responding surgeons believed that their method of preparation was well tolerated by patients, provided good cleansing, and was associated with few complications. Most patients were admitted one day before surgery. All respondents used perioperative antibiotics, with the most common pattern being a combination of oral and parenteral agents. Surgeons using PEG lavage did more colonic resections per month and were fewer years out of their residency. This current pattern of preoperative bowel preparation has changed from previous surveys. PMID- 2104796 TI - Effect of rioprostil, a methylprostaglandin E1 analog, on basal and stimulated plasma pancreatic hormone levels in man. AB - The effect of rioprostil, a methylprostaglandin E1 analog on circulating pancreatic hormones was evaluated in 13 healthy male subjects. Rioprostil administration, 300 micrograms twice daily resulted in a significant decrease of fasting insulin, C-peptide, glucagon, and pancreatic polypeptide. No change in fasting plasma glucose or somatostatin levels was observed. An oral glucose tolerance test induced similar increments in plasma glucose concentration before and during treatment, but a delayed rise of insulin and C-peptide levels occurred during the administration of the drug. On rioprostil, the glucose load no longer inhibited peripheral glucagon or somatostatin. Treatment with rioprostil remained without effect on mixed meal-induced changes in plasma glucose levels and concomitant increases in insulin, pancreatic polypeptide, and somatostatin levels. It is concluded that in healthy individuals rioprostil influences the basal and glucose-induced levels of glucagon, insulin, and somatostatin. In healthy men this effect did not, however, result in glucose intolerance. PMID- 2104797 TI - Healing of acetic acid-induced gastric ulcer and gastric mucosal PGI2 level in rats. AB - The present study was designed to investigate the changes in gastric mucosal PGI2 level accompanying the healing of acetic acid-induced gastric ulcers in rats. The ulcers, which were observed with an endoscope, were found to undergo periods of decrease, healing and exacerbation during the rat's lifetime. The phases were categorized as follows: (1) the reduction period (days 3-50 after ulcer induction, corresponding to 7-14 weeks of age), (2) healing period (days 35-150 after ulcer induction, corresponding to 12-29 weeks of age), (3) first exacerbation period (days 35-231 after ulcer induction, corresponding to 12-40 weeks of age), (4) inactive period (days 231-365 after ulcer induction, corresponding to 40-60 weeks of age), and (5) second exacerbation period (days 365-550 after ulcer induction, corresponding to 60-86 weeks of age). In normal rats, the level of gastric mucosal PGI2 gradually increased with aging between 7 and 20 weeks, then decreased up to 40 weeks. The PGI2 level in the 60-week-old rat did not differ from that in the 40-week-old rat. The PGI2 level was the lowest in the 86-week-old rat. In ulcer-bearing rats, the PGI2 level showed the same pattern of change as that in normal rats, but the level was higher. The above results indicated a marked decrease in PGI2 level between 20 and 40 weeks of age and between 60 and 86 weeks of age in normal and ulcer-bearing rats. These periods corresponded closely to the first and second exacerbation periods, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104798 TI - [Rocky Mountain spotted fever]. AB - After returning from a holiday in the USA a 24-year-old man fell ill with diarrhoea, high fever and marked rash including the palms of the hands and soles of the feet. When a history of a tick bite in the USA was elicited, a rickettsial infection was suspected. Treatment with doxycycline, 100 mg twice daily, was instituted finally and the fever slowly resolved. The patient became completely well again within four weeks. Serological tests confirmed the diagnosis of Rocky Mountain spotted fever. PMID- 2104799 TI - ras-induced c-fos expression and proliferation in living rat fibroblasts involves C-kinase activation and the serum response element pathway. AB - We have examined the early events involved in the proliferative activation of quiescent rat embryo fibroblasts by microinjection of oncogenic ras protein. Cells injected with ras show a transient expression of c-fos after 30-60 min visualized by immunofluorescence in the nucleus. This c-fos expression can be specifically suppressed by coinjection of a double-stranded oligonucleotide which corresponds to the serum response element (SRE) present in the c-fos promoter, implying that ras utilizes a pathway which activates the binding of serum response factor(s) (SRF) to SRE to induce c-fos transcription. Inhibition of this pathway also abolished ras-induced DNA synthesis indicating that the proliferative induction by ras requires expression of SRE-regulated genes. Both c fos induction and DNA synthesis were prevented when ras oncoprotein was injected into quiescent cells together with either antibodies against calcium phospholipid dependent protein kinase (C-kinase) or a synthetic peptide that specifically inhibits C-kinase. These data demonstrate the involvement of both functional C kinase and the SRE pathway in the activation of quiescent cells by ras and suggest a potential relationship in their mechanism of action. PMID- 2104800 TI - A mouse zinc finger gene which is transiently expressed during spermatogenesis. AB - Zinc finger proteins are polypeptides with sequence-specific, nucleic acid binding properties. Substantial evidence has established them as a class of trans acting molecules with regulatory roles in cellular growth and differentiation. We have screened an 11.5 day post coitum urogenital ridge cDNA library with an oligonucleotide encoding a sequence conserved between a variety of zinc finger proteins. By cDNA cloning and sequencing we show that a novel mouse gene, Zfp-35, encodes a protein with a block of 18 zinc finger domains and an N-terminal region rich in acidic residues. The 2.4 kb mRNA encoding this polypeptide is selectively expressed in adult testis, by comparison with other organs. We have analysed Zfp 35 expression in whole testes of sex-reversed mice, whole testes of prepuberal XY animals, germ cell fractions from XY adult testes and by in situ hybridization to sections from adult XY testes. Our studies show that a considerable increase in expression is restricted to spermatocytes at the pachytene stage of meiotic prophase. These experiments suggest that Zfp-35 may act to control gene activity during this particular stage of spermatogenesis. PMID- 2104801 TI - The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and shows a novel embryonic expression pattern. AB - We have identified a Drosophila zinc-finger protein, which binds to a number of sites in the transcriptional control regions of the pair-rule gene fushi-tarazu (ftz). The expression pattern of the mRNA that encodes this protein is essentially complementary to that of ftz both prior to blastoderm formation and during germband extension. We propose that the protein may function by repressing inappropriate segmentation gene transcription during embryogenesis. The gene encoding this ftz promoter-binding protein has been named tramtrack (ttk). PMID- 2104802 TI - The cecropin locus in Drosophila; a compact gene cluster involved in the response to infection. AB - Cecropins are antibacterial peptides that are synthesized in insects as a response to infection. As a first step towards a molecular study of the induction of this response, we have isolated genomic clones that cover the cecropin locus in Drosophila melanogaster. This locus was found to be unique, and it was mapped cytologically to the chromosomal location 99E. Sequence analysis showed it to be unusually compact, with three expressed genes and two pseudogenes within less than 4 kb of DNA, and with another homologous region less than 4 kb away. Two of the genes, A1 and A2, encode a product that is identical to the major cecropin from Sarcophaga peregrina, while the cecropin encoded by the B gene differs in five positions. Cecropin transcripts appear within an hour after bacteria have been injected into the hemocoel, reach a maximum after 2-6 h, and have almost disappeared again after 24 h. The B gene is induced in parallel with the A genes, but on a lower level. The cecropin genes were also induced when the flies were kept on food with the Drosophila pathogenic bacterium Serratia marcescens Db10 or its non-pathogenic derivative Db1140. PMID- 2104803 TI - Peroxisomal protein import is conserved between yeast, plants, insects and mammals. AB - We have previously demonstrated that firefly luciferase can be imported into peroxisomes of both insect and mammalian cells. To determine whether the process of protein transport into the peroxisome is functionally similar in more widely divergent eukaryotes, the cDNA encoding firefly luciferase was expressed in both yeast and plant cells. Luciferase was translocated into peroxisomes in each type of organism. Experiments were also performed to determine whether a yeast peroxisomal protein could be transported to peroxisomes in mammalian cells. We observed that a C-terminal segment of the yeast (Candida boidinii) peroxisomal protein PMP20 could act as a peroxisomal targeting signal in mammalian cells. These results suggest that at least one mechanism of protein translocation into peroxisomes has been conserved throughout eukaryotic evolution. PMID- 2104804 TI - Characterization of nuclear localizing sequences derived from yeast ribosomal protein L29. AB - Two particular seven-amino-acid segments from yeast ribosomal protein L29 caused a non-nuclear reporter protein to associate almost exclusively with the yeast nucleus. The two L29-derived nuclear localizing sequences were identical in five of the seven residues, many of which were basic amino acids. Generally, localization of the reporter protein was most impaired by replacement of the basic residues. A particular Arg residue was unique; substitution by any amino acid including Lys diminished nuclear localization of the reporter protein. In L29 the corresponding Arg 25----Lys substitution within the nuclear localizing sequence distal to the N-terminus was without effect, as evidence by normal rates of ribosome assembly and cell growth. However, the analogous Arg 8----Lys substitution within the localizing sequence proximal to the N-terminus led to greatly reduced rates of ribosome assembly and cell growth. Finally, when both localizing sequences contained the Arg----Lys substitution a still greater decrease in ribosome assembly and cell growth was observed. These results were as expected if the two short peptide sequences functioned in nuclear localization and/or assembly of yeast ribosomal protein L29. PMID- 2104805 TI - The role of ornithine decarboxylase and polyamines in regeneration of the frog sciatic nerve. AB - The current study examined both in vivo and in vitro the effects of alpha difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), on regeneration of sensory axons from a local crush of the adult frog sciatic nerve. If daily injections of DFMO started at the same time as crushing and continued throughout the regeneration period (7 days) the outgrowth in vivo of new sensory axons was reduced by about 30%. If DFMO injections started 2 days after crushing, the outgrowth distance did not differ from control values. The sensory axons of a cultured frog sciatic nerve with the attached spinal ganglia start to regenerate from a local crush applied 7 days after the start of the incubation. Five days after crushing the outgrowth distance was 4.5 mm. At the end of the culturing period (7 + 5 days) both the putrescine and spermidine concentrations in the ganglia had increased about 2.5 times, whereas the spermine concentration remained constant. The presence of 10 mM DFMO throughout the culturing period, 7 + 5 days, almost depleted putrescine and prevented the spermidine increase in the ganglia without affecting the regeneration distance. In the nerve putrescine was only reduced by 55% and the other polyamines were unaffected by DFMO. The results show that DFMO influences the early onset of regeneration in vivo. The in vitro results indicate that this is not due to a close mechanistic relationship between the perikaryonal ODC/polyamine system and nerve regeneration. The question of whether polyamines are of local importance for regeneration of the frog sciatic nerve cannot be answered by the present results. PMID- 2104806 TI - Equivalency of human menopausal gonadotropin and follicle-stimulating hormone stimulation after gonadotropin-releasing hormone agonist suppression. AB - This study compares the use of human menopausal gonadotropin (hMG) versus follicle-stimulating hormone (FSH), after gonadotropin-releasing hormone agonist (GnRH-a) suppression for in vitro fertilization. Thirty-seven patients were randomized to ovarian stimulation with either hMG or pure FSH. The GnRH-a leuprolide acetate was administered to all patients beginning in the midluteal phase of the prior cycle and continuing until the day of human chorionic gonadotropin (hCG) administration. There were no significant differences between hMG and FSH cycles with regard to the day of hCG administration, mean peak estradiol levels, number of ampules of medication used, and number of oocytes aspirated, embryos transferred, or pregnancies. We conclude that there is no significant difference between hMG and FSH stimulation when used in conjunction with GnRH-a. PMID- 2104807 TI - Gonadotropins and prolactin serum levels during the perimenopausal period: correlation with diverse factors. AB - We studied 490 women aged 35 to 55 years randomly selected from the urban population of Leon, Mexico. The mean age for the onset of menopause, calculated with a probit regression was 48.5 years. The median of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increased with the rate of menopause women, but the 10th percentile for both hormones did not increase above 15 IU/L in older groups. Meanwhile, prolactin did not change. In menopause women FSH correlated positively with cigarette smoking, and negatively with body mass index. Luteinizing hormone had negative correlation with the number of pregnancies. Most symptoms studied were not associated with menopause or gonadotropins levels, except hot flushes, and the empty nest syndrome. It was concluded that during menopause, FSH increases with the smoking habit, and decreases with overweight. PMID- 2104808 TI - Long-term suppression of ovarian function by a luteinizing-hormone releasing hormone agonist implant in patients with endometriosis. AB - Ten endometriosis patients received luteinizing hormone releasing hormone (LH-RH) agonist (buserelin) implant injections (6.6 mg subcutaneously) at days 0, 42, 84 and 126. Serum LH and follicle-stimulating hormone (FSH) were lowered by day 14. Luteinizing hormone remained at basal concentrations while FSH returned to values in the low-normal range of the menstrual cycle by day 35. At the end of the luteal phase during which treatment commenced, estrone and pregnanediol declined and remained at postmenopausal or early follicular phase values until days 305 to 460. Time to first ovulation ranged from 321 to 481 days after starting treatment. After the initial menstruation, only three instances of bleeding occurred during treatment. Pelvic pain was relieved or markedly reduced by day 42 and remained absent throughout the period of ovarian suppression. These results indicate the potential of a long-acting LH-RH agonist implant to form the basis for the treatment of symptomatic endometriosis. PMID- 2104809 TI - Patterns of serum-luteinizing hormone surges in stimulated cycles in relation to injections of human chorionic gonadotropin. AB - Endogenous-luteinizing hormone (LH) surges may complicate the management of in vitro fertilization cycles. To investigate the effects of LH surges after hormonal stimulation 53 IVF cycles were analyzed by assessing LH levels three times daily until egg collection. In 43% the LH rise started before the planned exogenous trigger for ovulation was given, in 11% the rise occurred simultaneously with and in 45% after the injection of human chorionic gonadotropin. Three main patterns of serum LH surges were identified: (A) low-LH tonus with straight increase to maximum; (B) low tonus with elevation before straight increase; (C) high tonus with large variations but no prominant peak. These patterns were not related to the follicular estradiol increase, luteal steroid concentrations or resulting pregnancy rates. PMID- 2104810 TI - Determination of insulin and insulin-like growth factors in the ovarian circulation. AB - Recent in vitro studies implicate the ovary as an extra-hepatic source of insulin like growth factors (IGFs) with production regulated by gonadotropins and local steroids. Because previous studies have failed to show any significant variations in IGF levels in peripheral blood during the menstrual cycle, we measured the concentrations of IGF-I, IGF-II, and insulin in ovarian and peripheral venous blood samples obtained simultaneously from nine women undergoing abdominal hysterectomy to obtain more detailed data on the ovarian contribution. A significant decreased ovarian gradient was found for IGF-II but not for IGF-I or insulin. Although there was no significant ovarian vein insulin gradient, insulin levels were higher in follicular than in luteal phase ovarian samples. These data suggest that IGF-II may be locally regulated by the ovary. Both insulin and IGFs may regulate ovarian function in vivo. PMID- 2104811 TI - Pregnancy rate and ovarian hyperstimulation after luteal human chorionic gonadotropin in in vitro fertilization stimulated with gonadotropin-releasing hormone analog and menotropins. AB - The value of luteal phase supplementation with human chorionic gonadotropin (hCG) was assessed after a combined protocol of ovarian stimulation, using a long acting gonadotropin releasing hormone analog (GnRH-a) and human menopausal gonadotropins (hMG), in a randomized prospective study of 36 consecutive cycles in an in vitro fertilization (IVF) program. The patients were allocated on the transfer day to either luteal phase supplementation with hCG (Group A, n = 18) or none (Group B, n = 18). Nine patients of Group A conceived as compared with 3 in Group B. Five patients, all in Group A, developed ovarian hyperstimulation syndrome (OHSS) (3 moderate and 2 severe forms). Analysis of the hormonal profiles disclosed similar progesterone (P), estradiol (E2), and E2/P ratio up to the 6th post ovum pick-up day. Then, E2 and mainly P levels decreased only in Group B resulting in a rising E2/P ratio. These findings stress the importance of luteal support in IVF cycles treated with GnRH-a. In light of the increased risk of OHSS among hCG treated patients, further studies are needed to assess the optimal preparation needed. PMID- 2104812 TI - In vitro regulation of neuronal morphogenesis and polarity by astrocyte-derived factors. AB - Mesencephalic neurons were cultured from 2 to 5 days in mesencephalic (CM Gmes) or striatal (CM Gstr) astrocyte conditioned media or in the soluble (S100) and insoluble (P100) fractions prepared from these media by ultracentrifugation. CM Gmes as well as all soluble fractions induced dendritic and axonal elongation, whereas CM Gstr and the insoluble fractions promoted axonal growth only. The study of the shape of the neuronal cell bodies and the measurement of their adhesion to the substratum revealed that axons elongated under low adhesion conditions, but that dendrite growth was highly dependent upon adhesion and spreading of the neuronal soma. This different dependency of axonal and dendritic elongation upon spreading is explained by a model in which we consider the respective viscosities of axons and dendrites. From these observations and speculations we propose that axons and dendrites have different modes of elongation and that the primary effect of the astrocyte-derived factors capable of regulating neuronal polarity is to modify the adhesion of the neurons to their culture substratum. PMID- 2104813 TI - Precocious loss of cortical granules during mouse oocyte meiotic maturation and correlation with an egg-induced modification of the zona pellucida. AB - Fertilization results in cortical granule exocytosis, which is thought to be involved in modifications of the zona pellucida that constitute the zona pellucida block to polyspermy. A previous report demonstrated that a decrease in the number of Lens culinaris agglutinin-staining granules, which are likely to be cortical granules, occurred during in vivo mouse oocyte maturation with arrest at metaphase II, as well as the formation of a cortical granule-free domain in the area of the metaphase II spindle (T. Ducibella, E. Anderson, D.F. Albertini, J. Aalberg, and S. Rangarajan, 1988, Dev. Biol. 130, 184-197). We extend these observations by reporting here that germinal vesicle-intact oocytes matured in vitro to metaphase II in either the absence or the presence of serum develop a cortical granule-free domain and have reduced numbers of cortical granules when compared to germinal vesicle-intact oocytes; these changes are similar to those of oocytes matured in vivo. The reduction in the number of cortical granules requires germinal vesicle breakdown, since it is prevented by dibutyryl cAMP, which inhibits germinal vesicle breakdown in vitro. The ability of oocytes to respond to the calcium ionophore A23187 with a reduction in the number of cortical granules is also associated with meiotic maturation and develops between 7 and 12 hr after initiation of maturation. The maturation-associated reduction in the number of cortical granules is likely to represent cortical granule exocytosis, since this reduction is accompanied by the formation of a cortical granule-free domain and a conversion of ZP2 to ZP2f when the oocytes are matured in vitro in serum-free medium; this zona pellucida modification occurs following fertilization and is thought to be due to cortical granule exocytosis. In contrast, the loss of cortical granules and development of the cortical granule free domain of oocytes matured in vitro in the presence of serum is not accompanied by the modification of ZP2. The inhibitory effect of serum on the ZP2 modification may afford in vivo a physiological mechanism to prevent a precocious modification of the zona pellucida that could result in a premature block to polyspermy and hence inhibit fertilization. PMID- 2104814 TI - Central nervous system action of peptides to influence gastrointestinal motor function. AB - The central action of peptides to influence GI motility in experimental animals is summarized in Table 1. TRH stimulates gastric, intestinal, and colonic contractility in rats and in several experimental species. A number of peptides including calcitonin, CGRP, neurotensin, NPY, and mu opioid peptides act centrally to induce a fasted MMC pattern of intestinal motility in fed animals while GRF and substance P shorten its duration. The dorsal vagal complex is site of action for TRH-, bombesin-, and somatostatin-induced stimulation of gastric contractility, and for CCK-, oxytocin- and substance P-induced decrease in gastric contractions or intraluminal pressure. The mechanisms through which TRH, bombesin, calcitonin, neurotensin, CCK, and oxytocin alter GI motility are vagally mediated. An involvement of central peptidergic neurons in the regulation of gut motility has recently been demonstrated in Aplysia, indicating that such regulatory mechanisms are important in the phylogenesis. Alterations of the pattern of GI motor activity are associated with functional changes in transit. TRH is so far the only centrally acting peptide stimulating simultaneously gastric, intestinal, and colonic transit in various animals species. Opioid peptides acting on mu receptor subtypes in the brain exert the opposite effect and inhibit concomitantly gastric, intestinal, and colonic transit. Bombesin and CRF were found to act centrally to inhibit gastric and intestinal transit and to stimulate colonic transit in the rat. The antitransit effect of calcitonin and CGRP is limited to the stomach and small intestine. The delay in GI transit is associated with reduced GI contractility for most of the peptides except central bombesin that increases GI motility. Nothing is known about brain sites through which these peptides act to alter gastric emptying and colonic transit. Regarding brain sites influencing intestinal transit, TRH-induced stimulation of intestinal transit in the rat is localized in the lateral and medial hypothalamus and medial septum. The periaqueductal gray matter is a responsive site for mu receptor agonist- and neurotensin-induced inhibition of intestinal transit. The neural pathways from the brain to the gut whereby these peptides express their stimulatory or inhibitory effects on GI transit is vagal dependent with the exception of calcitonin. It is not known whether the vagally mediated inhibition of GI transit by these peptides results from a decrease activity of vagal preganglionic fibers synapsing with excitatory myenteric neurons or an activation of vagal preganglionic neurons synapsing with inhibitory myenteric neurons. The lack of specific antagonists for these peptides has hampered the assessment of their physiological role.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2104815 TI - Neuropeptide Y inhibits thyrotropin-releasing hormone-induced stimulation of melanotropin release from the intermediate lobe of the frog pituitary. AB - Previous studies have shown that the release of melanotropin from frog neurointermediate lobes is under the control of two neuropeptides: thyrotropin releasing hormone (TRH) stimulates, while neuropeptide Y (NPY) inhibits alpha melanocyte-stimulating hormone (alpha-MSH) secretion from intact neurointermediate lobes in vitro. The aim of the present study was to investigate possible interactions between the two regulatory peptides at the pituitary level. Whole neurointermediate lobes or acutely dispersed pars intermedia cells from Rana ridibunda were perifused in vitro for 2 to 7.5 hr and the concentrations of alpha-MSH released into the effluent perifusate were monitored by radioimmunoassay. Administration of TRH (10(-7) M) or NPY (10(-7) M) to dispersed cells induced, respectively, marked stimulation or inhibition of alpha-MSH release. The effects of the two neuropeptides were similar to those observed using intact neurointermediate lobes, suggesting that TRH and NPY act directly on melanotropic cells. Perifused whole neurointermediate lobes were exposed to NPY (10(-8) to 3 x 10(-7) M) for 120 min and a single dose of TRH (10(-8) M) was administered during the prolonged infusion of NPY. Using this procedure, we observed a dose-dependent inhibition of TRH-evoked alpha-MSH release. These data support the concept that TRH and NPY act through a common intracellular pathway to regulate alpha-MSH release. PMID- 2104816 TI - Immunocytochemical localization of the subunits of glycoprotein hormones (LH, FSH, and TSH) in the bullfrog pituitary gland using monoclonal antibodies and polyclonal antiserum. AB - Using beta and alpha subunits of bullfrog follitropin (FSH) III (pI 6.2), which were highly purified by HPLC, we generated three monoclonal antibodies (MCAs) to FSH beta subunit (FSH beta) and six to FSH alpha subunit (FSH alpha). They were produced by hybridomas derived from the myeloma X63.Ag8.653 and spleen lymphocytes from mice immunized with each subunit. Non-competitive binding tests revealed that one of the MCAs against FSH beta (BF3B25) bound strongly to intact FSH and its beta subunit, but not FSH alpha, lutropin (LH), LH alpha, and LH beta. The immunoblotting results also showed a similar immunological specificity for BF3B25. Cross-reactivity of bullfrog FSH against BF3B25 was 19.4%, when compared with FSH beta in the competitive inhibition assay system. On the other hand, noncompetitive binding tests and immunoblotting results showed that one of the MCAs against FSH alpha (BF3A20) bound strongly to intact LH and FSH and their alpha subunits, but not their beta subunits. The inhibition curves obtained using the alpha subunits of LH and FSH were similar. In the sexually mature bullfrog pituitary, immunoreactive FSH cells stained with MCA BF3B25 were distributed throughout the pars distalis, except for the rostral region, and were polygonal in shape, with well-developed cytoplasm. With respect to distribution and histological characteristics, the immunoreactive LH cells were very similar to the immunoreactive FSH cells when consecutive sections were stained with LH beta specific MCA (BL4B11). However, immunoreactive TSH cells, revealed by anti-human TSH beta serum, formed clusters in the ventrocentral region of the pars distalis. In young adult pituitary, almost all of the gonadotrophs showed the coexistence of FSH and LH, but some gonadotrophs contained only FSH. The number of immunoreactive alpha-subunit cells stained by BF3A20 was always higher than the sum of the numbers of cells stained by the three beta-subunit-specific antibodies. PMID- 2104817 TI - The physician's role in nursing home care: an overview. AB - Providing effective, high-quality care in the nursing home is an important medical responsibility. Physicians must have knowledge of the nursing home environment, medical problems common in nursing home patients, and basic aspects of care required in the elderly. While the medical director of a nursing home must set and maintain the standard of care, attending physicians need to understand the clinically relevant differences between young and old people, be skilled in geriatric assessment, prescribe medications knowledgeably and with restraint, respond promptly to changes in the patient's status, and carefully document medical observations and care plans. PMID- 2104818 TI - Home health care: how long must physicians work for free? PMID- 2104819 TI - Hexamethylmelamine as a single second-line agent in ovarian cancer. AB - Fifty-two patients with advanced ovarian cancer were treated with single-agent hexamethylmelamine (HMM), 260 mg/m2 po per day for 14 days followed by 14 days off drug. All patients had been previously treated with chemotherapy. Of these patients, 92% (48/52) received cisplatin and cyclophosphamide +/- doxorubicin prior to hexamethylmelamine. Two additional patients received other cisplatin based regimens. Fifteen percent (8/52) were found to have no evidence of disease (NED) at the completion of treatment with HMM. Five of these patients are alive at 12 to 65 months (median follow-up of 32 months); one patient died at 41 months of an intercurrent illness with no clinical evidence of recurrence; two patients died of recurrent tumor at 21 and 31 months. The median survival of the series of 52 patients is 11 months: 9 months for patients who did not respond versus 41 months for patients with NED post-HMM (P less than 0.05). The regimen was well tolerated: moderate gastrointestinal toxicity was reported by 8 patients; only one patient reported severe gastrointestinal toxicity. Moderate neurologic toxicity (primarily sensory) was reported by 5 patients, 3 patients experienced white counts less than 2000 or platelet counts less than 100,000, and no patient sustained severe hematologic toxicity. This moderate-dose intermittent regimen was associated with moderate toxicity and was well accepted by patients. The overall response is comparable to or higher than that reported for more toxic chemotherapy regimes. Based on these data and those recently reported by other authors, hexamethylmelamine should be considered in the treatment of recurrent ovarian cancer. PMID- 2104820 TI - Hemodynamic mechanisms of emerging portal hypertension caused by schistosomiasis in the hamster. AB - A hamster model of schistosomiasis has provided the first opportunity to sequentially examine the early phases of the development of portal hypertension in a natural model of chronic liver disease. Groups of hamsters were infected with 50 cercariae of Schistosoma mansoni and underwent hemodynamic evaluation at intervals of 5, 8, 12 and 20 wk after infection. A progressive rise in intrahepatic resistance (from 4.0 +/- 0.4 to 8.4 +/- 1.0 mm Hg min.ml-1.gm liver weight [p less than 0.01]) appeared to play a major role in the initial stages of evolving portal hypertension. A gradual decline in portal blood flow (from 2.1 +/ 0.3 to 1.3 +/- 0.1 ml.min-1.gm-1 liver weight [p less than 0.01]) was only partially compensated for by an increase in hepatic arterial flow. Accordingly, by week 20, total hepatic blood flow decreased 23%. Liver weight that increased markedly between 5 and 12 wk after infection, as a result of the acute accumulation of obstructing granulomas, stabilized between wk 12 and 20, while a gradual but progressive rise in hepatic collagen content was seen. Portal pressure increased 75% during the study period. Chronic examination of this natural model should help define the pathogenesis of the complications of portal hypertension and contribute to the basis for effective intervention in this disease process. PMID- 2104821 TI - Hospitalization for psychiatric illness under Medicare, 1985. AB - National and state-level data on Medicare-covered hospital discharges after treatment for psychiatric illness in 1985 were analyzed to determine the distribution of cases among various types of psychiatric and general hospitals. In most states, 80 to 90 percent of Medicare patients with psychiatric conditions received care in a setting that provided specialized treatment for psychiatric illness. However, the distribution of discharges among public and private psychiatric hospitals and general hospitals with psychiatric units varied substantially among states. Between 1984, the first year of Medicare's prospective payment system, and 1985, the number of discharges decreased overall, and a shift toward treatment in specialized psychiatric facilities and toward settings exempt from the prospective payment system was apparent. PMID- 2104822 TI - Need grows for children's services. PMID- 2104824 TI - Listeria continues to cause problems. PMID- 2104823 TI - Synaptophysin: a sensitive and specific marker for ganglion cells in central nervous system neoplasms. AB - Synaptophysin, a 38-kilodalton glycoprotein found in synaptic vesicle membranes, has been shown to be a sensitive marker of neuroendocrine differentiation in non central nervous system (CNS) tumors. We analyzed the patterns of synaptophysin immunoreactivity in CNS neoplasms in comparison with various normal CNS sites in biopsies. Normal gray matter structures all showed a diffuse punctate granular pattern of neuropil staining without staining of neuronal cell bodies. In contrast, neoplastic ganglion cells in 18 of 18 gangliogliomas/gangliocytomas showed intense immunoreactivity outlinging the borders of the cell bodies. Focal staining was also seen in five of 16 primitive neuroectodermal tumors and in one of three central neurocytomas, but these tumors had a finely granular neuropil pattern of immunoreactivity more like that of normal gray matter than like that of the gangliogliomas. All 35 examples of pure gliomas of various types showed no immunoreactivity. Our data highlight synaptophysin as a sensitive and specific marker of both neuronal lineage and neoplastic character in gangliogliomas. PMID- 2104825 TI - Enhanced intestinal permeability to 51Cr-labeled EDTA in dogs with small intestinal disease. AB - Intestinal permeability in dogs with small intestinal disease was measured by quantitation of 24-hour urinary excretion of 51Cr-labeled EDTA following intragastric administration. Permeability was high in dogs with a variety of naturally acquired small intestinal diseases including wheat-sensitive enteropathy of Irish Setters, small intestinal bacterial over-growth, and giardiasis, and permeability was decreased after successful treatment. These findings indicate that the assessment of intestinal permeability may be a useful technique for detecting small intestinal disease and for monitoring the efficacy of treatment in dogs. PMID- 2104826 TI - Amino acid sequence around the serine phosphorylated by casein kinase II in brain myosin heavy chain. AB - Casein kinase II from bovine brain transfers about one mole of phosphate to a serine residue near the COOH terminus of the heavy chain of myosin isolated from bovine brain. We have purified and characterized a peptide that contains this phosphoserine. The peptide was generated by chymotryptic and thermolytic digestion and was isolated by gel filtration, Fe3+ affinity chromatography, and reverse-phase high pressure liquid chromatography. Its sequence, Leu-Glu-Leu Ser(PO4)-Asp-Asp-Asp-Asp-Glu-Ser-Lys-Ala-Ser-(Xaa)-Ile-Asn-Glu-Thr- Gln-Pro-Pro Gln, shows that the Ser(PO4) is in an acidic environment, as is typical for casein kinase II phosphorylation sites. The "hydrophobic repeat" typical of alpha helical coiled-coils is absent, suggesting that the sequence is part of a non helical "tail piece" of the heavy chain. A synthetic peptide corresponding to residues 1-9 is shown to be an effective substrate for casein kinase II. PMID- 2104827 TI - Isolation to homogeneity and partial characterization of a histo-blood group A defined Fuc alpha 1----2Gal alpha 1----3-N-acetylgalactosaminyltransferase from human lung tissue. AB - The soluble histo-blood group A glycosyltransferase (Fuc alpha 1----Gal alpha 1-- -3-N-acetylgalactosaminyltransferase) was purified approximately 600,000-fold to homogeneity from human lung tissue. The enzyme was solubilized in 1% Triton X 100, partially purified by affinity chromatography on Sepharose 4B, and eluted with UDP. Final purification was obtained by twice repeated fast protein liquid chromatography ion exchange (Mono STM) with NaCl gradient elution and reverse phase chromatography (proRPC) with acetonitrile gradient elution. Identity of the purified protein was established by (i) demonstration of the putative A transferase protein only in affinity-purified extracts of A but not O individuals, and (ii) specific immunoprecipitation of enzyme activity and putative protein with monoclonal antibodies. Sodium dodecyl sulfate electrophoresis revealed a single protein band with apparent Mr of approximately 40,000 under both reducing and nonreducing conditions. Digestion with N-glycanase yielded a reduction in Mr of approximately 6,000 (estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis), suggesting that the A transferase is a glycoprotein with N-linked carbohydrate chains. Amino acid composition and N terminal amino acid sequence of the intact transferase, as well as of peptides released by endolysyl peptidase digest or cyanogen bromide cleavage, are presented. PMID- 2104828 TI - Cloning and characterization of DNA complementary to human UDP-GalNAc: Fuc alpha 1----2Gal alpha 1----3GalNAc transferase (histo-blood group A transferase) mRNA. AB - Based on the partial amino acid sequence, the cDNA encoding UDP-GalNAc:Fuc alpha 1----2Gal alpha 1----3GalNAc transferase, the specific primary gene product of histo-blood group A gene (A transferase), was cloned and sequenced. Poly(A)+ RNA from human stomach cancer cell line MKN45, expressing high levels of A antigen, was used for construction of a lambda gt10 cDNA library. Degenerate synthetic oligodeoxynucleotides were used for polymerase chain reactions to detect the presence of the sequence of interest in cDNA (presence test) and to identify the correct clones (identification test) after screening the library with a radiolabeled polymerase chain reaction amplified fragment. Nucleotide sequence analysis revealed a coding region of 1062 base pairs encoding a protein of 41 kDa. Hydrophobicity plot analysis shows the existence of three domains: N terminal short stretch, transmembranous hydrophobic region, and a long C-terminal domain (a feature common to all glycosyltransferases cloned so far). Southern hybridization analysis has shown that this DNA does not represent a multigene family. No restriction fragment length polymorphism was found to correlate with ABO blood group type. Bands were detected in Northern hybridization of mRNAs from cell lines expressing A, B, AB, or H antigens. These results suggest that sequences of ABO genes are essentially very similar (with minimal differences), and the inability of the O gene to encode A or B transferases is probably due to structural differences rather than A or B transferase expression failure. PMID- 2104829 TI - A1 adenosine receptor of rat testis membranes. Purification and partial characterization. AB - Purification of an A1 adenosine receptor of rat testes was performed using a newly developed affinity chromatography system (Nakata, H. (1989) Mol. Pharmacol. 35, 780-786). The A1 adenosine receptor was solubilized with digitonin from rat testicular membranes and then purified more than 25,000-fold by sequential use of affinity chromatography on xanthine amine congener-immobilized agarose, hydroxylapatite chromatography, re-affinity chromatography on xanthine amine congener-agarose, and finally gel permeation chromatography on TSK-3000SW. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the final preparation showed a single broad band of Mr 41,000 by autoradiography after radioiodination. This Mr 41,000 peptide was also specifically labeled with an A1 adenosine receptor affinity labeling reagent. A high affinity A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-[3H]dipropylxanthine, bound saturably to the purified receptor with a KD of approximately 1.4 nM. The purified receptor also showed essentially the same specificity for adenosine agonists and antagonists as the unpurified receptor preparations, although the affinities of the purified adenosine receptor for agonists were significantly low compared to those of unpurified receptor preparations indicating that the purified A1 adenosine receptor exists as a low agonist-high antagonist affinity state. Deglycosylation of the purified testis adenosine A1 receptors with endoglycosidase F produced an increase in the mobility of the receptor protein to an apparent Mr 30,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, similar to that of deglycosylated A1 adenosine receptors of rat brain membranes. Peptide maps of the purified testis and brain A1 adenosine receptors using trypsin and V8 protease suggest that these receptors show some structural homologies. PMID- 2104830 TI - Primary sequence of the EcoRII endonuclease and properties of its fusions with beta-galactosidase. AB - The EcoRII endonuclease cleaves DNA containing the sequence CC(A/T)GG before the first cytosine. The methylation of the second cytosine in the sequence by either the EcoRII methylase or Dcm, a chromosomally coded protein in Escherichia coli, inhibits the cleavage. The gene for the EcoRII endonuclease was mapped by analysis of derivatives containing linker insertions, transposon insertions, and restriction fragment deletions. Surprisingly, plasmids carrying the wild-type endonuclease gene and the EcoRII methylase gene interrupted by transposon insertions appeared to be lethal to dcm+ strains of E. coli. We conclude that not all the EcoRII/Dcm recognition sites in the cellular DNA are methylated in dcm+ strains. The DNA sequence of a 1650-base pair fragment containing the endonuclease gene was determined. It revealed an open reading frame that could code for a 45.6-kDa protein. This predicted size is consistent with the known size of the endonuclease monomer (44 kDa). The endonuclease and methylase genes appear to be transcribed convergently from separate promoters. The reading frame of the endonuclease gene was confirmed at three points by generating random protein fusions between the endonuclease and beta-galactosidase, followed by an analysis of the sequence at the junctions. One of these fusions is missing 18 COOH-terminal amino acids of the endonuclease but still displays significant ability to restrict incoming phage in addition to beta-galactosidase activity. No striking similarity between the sequence of the endonuclease and any other protein in the PIR data base was found. The knowledge of the primary sequence of the endonuclease and the availability of the various constructs involving its gene should be helpful in the study of the interaction of the enzyme with its substrate DNA. PMID- 2104831 TI - Characterization of a nonglycosylated single chain urinary plasminogen activator secreted from yeast. AB - Using site-directed mutagenesis, we have changed the asparagine in human single chain urinary plasminogen activator (u-PA) at position 302 to an alanine. This alteration removes the only known amino acid residue glycosylated in the protein. The single-chain u-PA containing an alanine residue at position 302 instead of asparagine (scu-PA(N302A] cDNA gene was expressed in the yeast Saccharomyces cerevisiae. Secretion of the protein product into the culture broth was achieved by replacing the human secretion signal codons with those from yeast invertase, adding a yeast promoter from the constitutively expressed glycolytic genes triosephosphate isomerase or phosphoglycerate kinase, and integrating multiple copies of these transcriptional units into the genome of yeast strains carrying the "supersecreting" mutation ssc1. When fermented in a fed-batch mode, these recombinant baker's yeast strains secreted scu-PA(N302A) in a strongly growth associated manner. Greater than 90% of the u-PA found in the culture broth was in the single-chain form. Scu-PA(N302A) was purified to homogeneity using two chromatography steps. The purified protein had a molecular weight of 47,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and lacked any detectable N-linked glycosylation. The in vitro fibrinolytic properties of scu-PA(N302A) were found to be essentially equivalent to those of natural single-chain u-PA derived from the human kidney cell line TCL-598. Since scu-PA(N302A) lacks the immunogenic N-linked carbohydrate pattern of yeast, it may be a useful therapeutic agent which can be produced economically by yeast fermentation. PMID- 2104832 TI - Binding of human factor VIII to phospholipid vesicles. AB - Factor VIII, a protein cofactor involved in blood coagulation, functions in vitro on a phospholipid membrane surface to greatly increase the rate of factor X activation by factor IXa. Using gel filtration, rapid sedimentation, and resonance energy transfer we have studied the interaction of recombinant-derived human factor VIII with small and large unilamellar phospholipid vesicles composed of phosphatidylserine and phosphatidylcholine. Resonance energy transfer, from intrinsic fluorophores in factor VIII to dansyl-phosphatidylethanolamine incorporated into vesicles, has been adapted for quantitative equilibrium measurements. Factor VIII binds rapidly and reversibly to small and large vesicles. At 8 degrees C the interaction of factor VIII with small vesicles fits a simple bimolecular model with a KD of 2 nM and a phospholipid binding site defined by 180 phospholipid monomers. At 25 degrees C the binding of factor VIII to small vesicles containing 20% phosphatidylserine can be described by an apparent KD of 4 nM; the phospholipid/protein ratio at saturation was 170. Binding to large vesicles was demonstrated with a KD of 2 nM and a phospholipid/protein ratio at saturation of 385. Binding was dependent upon the phosphatidylserine mole fraction and was nonlinear from 0 to 30% phosphatidylserine content. A direct comparison of factor VIII and factor V binding indicated that the affinity of factor V to phospholipid vesicles was equivalent to that of factor VIII and that the phosphatidylserine requirement was lower. A model is proposed to explain the nonlinear phosphatidylserine dependence of binding for factor VIII. PMID- 2104833 TI - Isolation and characterization of Patnopecten mid-gut gland endo-beta-xylosidase active on peptidochondroitin sulfate. AB - An endo-beta-xylosidase acting on the linkage region of peptidochondroitin sulfate was isolated from the mid-gut gland of the mollusc Patnopecten and purified about 375-fold, using a combination of ammonium sulfate fractionation, gel filtration on Sephacryl S-200, and DEAE-Sephacel chromatography. The pH optimum and the isoelectric point of this enzyme were 4.0 and 7.0, respectively. The molecular weight, estimated by gel filtration through Sephacryl S-200, was 78,000. The purified enzyme was completely free from protease, exoglycosidases, sulfatase, and phosphatase. This enzyme hydrolyzed the xylosyl serine linkage of the linkage region of various glycosaminoglycans, that is chondroitin sulfate, dermatan sulfate and heparan sulfate, all possessing a very small peptide segment, but not proteoglycans. It was concluded that this endo-beta-xylosidase was involved in the catabolism of proteoglycans. PMID- 2104834 TI - Identification of an intracellular pool of glucose transporters from basal and insulin-stimulated rat skeletal muscle. AB - The purpose of this study was to simultaneously isolate skeletal muscle plasma and microsomal membranes from the hind limbs of male Sprague-Dawley rats perfused either in the absence or presence of 20 milliunits/ml insulin and to determine the effect of insulin on the number and distribution of glucose transporters in these membrane fractions. Insulin increased hind limb glucose uptake greater than 3-fold (2.4 +/- 0.7 versus 9.2 +/- 1.0 mumol/g x h, p less than 0.001). Plasma membrane glucose transporter number, measured by cytochalasin B binding, increased 2-fold (9.1 +/- 1.0 to 20.4 +/- 3.1 pmol/mg protein, p less than 0.005) in insulin-stimulated muscle while microsomal membrane transporters decreased significantly (14.8 +/- 1.6 to 9.8 +/- 1.4 pmol/mg protein, p less than 0.05). No change in the dissociation constant (Kd approximately 120 nm) was observed. K+ stimulated-p-nitrophenol phosphatase, 5'-nucleotidase, and galactosyltransferase specific activity, enrichment, and recovery in the plasma and microsomal membrane fractions were not altered by insulin treatment. Western blot analysis using the monoclonal antibody mAb 1F8 (specific for the insulin-regulatable glucose transporter) demonstrated increased glucose transporter densities in plasma membranes from insulin-treated hind limb skeletal muscle compared with untreated tissues, while microsomal membranes from the insulin-treated hind limb skeletal muscle had a concomitant decrease in transporter density. We conclude that the increase in plasma membrane glucose transporters explains, at least in part, the increase in glucose uptake associated with insulin stimulation of hind limb skeletal muscle. Our data further suggest that these recruited transporters originate from an intracellular microsomal pool, consistent with the translocation hypothesis. PMID- 2104835 TI - Tubulin binds specifically to the signal-transducing proteins, Gs alpha and Gi alpha 1. AB - Participation of cytoskeletal elements in regulation of hormonal response and responsiveness has been suggested by several laboratories. Addition of dimeric tubulin to rat cerebral cortex synaptic membranes causes stable inhibition of adenylyl cyclase, and the molecular basis for this effect appears to require a direct interaction between tubulin and G proteins. To test whether such tubulin-G protein interaction occurred, several purified G proteins were bound to nitrocellulose, and 125I-tubulin overlay studies were performed. 125I-Tubulin bound to the alpha subunits of Gs and Gil with high specificity and an apparent Kd of approximately 130 nM. Other G protein alpha subunits (alpha i2, alpha i3, alpha 0, and transducin) displayed a much lower affinity for tubulin, despite the much closer relationship of those proteins to alpha il than to alpha s. Association of beta gamma subunits with alpha il or alpha s did not alter the binding of tubulin to these G protein heterotrimers, and the binding of a hydrolysis-resistant GTP analog to the alpha subunits was similarly without effect. These results suggest that tubulin forms complexes with specific G proteins and these complexes might provide a locus for the interaction of cytoskeletal components and signal transduction cascades. These results also provide evidence of a functional distinction among the closely related alpha i subtypes. PMID- 2104836 TI - An engineered change in substrate specificity of ribulosebisphosphate carboxylase/oxygenase. AB - The potential for altering the specificity of ribulosebisphosphate carboxylase/oxygenase toward gaseous substrates is explored through a modest perturbation of the active site microenvironment. Specifically, replacement of active site Glu-48 with carboxy-methylcysteine is achieved in a two-step process in which the catalytically incompetent Cys-48 mutant protein is first generated and then treated with iodoacetic acid. This regimen of concerted site-directed mutagenesis and chemical modification, effectively lengthening the glutamyl side chain by insertion of a sulfur atom between the beta- and gamma-methylene groups, results in a protein possessing 4-6% of wild-type carboxylase activity. Concomitantly, the engineered enzyme exhibits a specificity factor 5-fold lower than that of wild-type enzyme. This represents the first example of a major change in substrate specificity, albeit in favor of oxygenation, effected by structural alteration of an active site side chain. PMID- 2104837 TI - The primary structure of a halorhodopsin from Natronobacterium pharaonis. Structural, functional and evolutionary implications for bacterial rhodopsins and halorhodopsins. AB - We cloned and sequenced the gene coding for the polypeptide of a halorhodopsin in Natronobacterium pharaonis (named here pharaonis halorhodopsin). Peptide sequencing of cyanogen bromide fragments, and immunoreactions of the protein and synthetic peptides derived from the COOH-terminal gene sequence, confirmed that the open reading frame is the structural gene for the pharaonis halorhodopsin polypeptide. The flanking DNA sequences, as well as those for other bacterial rhodopsins, were compared to previously proposed archaebacterial consensus sequences. In pairwise comparisons of the open reading frame with DNA sequences for bacterio-opsin and halo-opsin from Halobacterium halobium, silent divergences (mutations/nucleotide at codon positions which do not result in amino acid changes) were calculated. These indicate very considerable evolutionary distance between each pair of genes. In spite of this, the three protein sequences show extensive similarities, indicating strong selective pressures. Conserved and conservatively replaced amino acid residues in all three proteins identify general features essential for ion-motive bacterial rhodopsins, responsible for overall structure and chromophore properties. Comparison of the bacteriorhodopsin sequence with those of the two halorhodopsins, on the other hand, identifies features involved in their specific (proton and chloride ion) transport functions. PMID- 2104838 TI - Properties and photochemistry of a halorhodopsin from the haloalkalophile, Natronobacterium pharaonis. AB - Pharaonis halorhodopsin is a light-driven transport system for chloride, similarly to the previously described halorhodopsin, but we find that it transports nitrate as effectively as chloride. We studied the photoreactions of the purified, detergent-solubilized pharaonis pigment with a gated multichannel analyzer. At a physiological salt concentration (4 M NaCl), the absorption spectra and rate constants of rise and decay for intermediates of the photocycle were similar to those for halorhodopsin. In buffer containing nitrate, halorhodopsin exhibits a second, truncated photocycle; this difference in the photoreaction of the pigment occurs when an anion is bound in such a way as to preclude transport. As expected from the lack of anion specificity in the transport, the photocycle of pharaonis halorhodopsin was nearly unaffected by replacement of chloride with nitrate. All presumed buried positively charged residues, which might play a role in anion binding, are conserved in the two pigments. At the extracellular end of the presumed helix C, however, an arginine residue is found in halorhodopsin, but not in pharaonis halorhodopsin, and an arginine-rich segment between the presumed helices A and B in halorhodopsin is replaced by a less positively charged sequence in pharaonis halorhodopsin (Lanyi, J. K., Duschl, A., Hatfield, G. W., May, K., and Oesterhelt, D. (1990) J. Biol. Chem. 265, 1253-1260). One or both of these alterations may explain the difference in the anion selectivity of the two proteins. PMID- 2104839 TI - Left-handed Z-DNA and intramolecular triplex formation at the site of an unequal sister chromatid exchange. AB - An unequal sister chromatid exchange (USCE) in the mouse myeloma cell line MPC-11 between 3' regions of the C gamma 2a and C gamma 2b heavy chain genes results in duplication of the C gamma 2a heavy chain gene and generation of a novel recombination joint. The USCE occurs between (TC)n tracts adjacent to alternating purine-pyrimidine tracts. We have investigated the capacity of both the donor regions and the recombinant product involved in this event to adopt left-handed Z DNA and intramolecular triplexes. The results of chemical probing with diethylpyrocarbonate and osmium tetroxide at the base pair level demonstrate that under the influence of negative supercoiling the alternating purine-pyrimidine regions of these plasmids can adopt Z-DNA at neutral pH, and the oligopurine.oligopyrimidine (pur.pyr) regions of these regions can adopt intramolecular triplexes at low pH (less than or equal to pH 6.0). At intermediate pH values, mixtures of both structures are present. Increasing the negative superhelical density of the plasmid does not increase the amount of triplex present at neutral pH indicating that the presence of long Z-DNA segments adjacent to pur.pyr tract prevents intramolecular triplex formation. In summary, we conclude that the sequences involved in the USCE can form either an intramolecular triplex in the (TC)n tract or Z-DNA in the alternating purine pyrimidine tract and that Z-DNA will predominate under physiological conditions. The presence of segments which adopt Z-DNA at a site of USCE suggests that formation of this structure may enhance recombination between adjacent pur.pyr tracts. PMID- 2104840 TI - Progesterone and 17 alpha-hydroxyprogesterone. Novel stimulators of calcium influx in human sperm. AB - Progesterone and 17 alpha-hydroxyprogesterone (but not other steroids such as testosterone, corticosterone, beta-estradiol, estrone, dehydroepiandrosterone, 20 alpha-hydroxypregnen-3-one, androstenedione, and pregnenolone) were shown to cause an immediate increase, in free cytosolic calcium ([Ca2+]i) in both capacitated and noncapacitated human sperm, using the fluorescent indicator fura 2. Significant increases in [Ca2+]i were observed with 10 ng/ml progesterone, while maximum effects were seen with 1 microgram/ml progesterone. Two other steroids 11 beta-hydroxyprogesterone and 5 alpha-pregnane-3,20-dione exhibited significant activity to increase [Ca2+]i. This increase in [Ca2+]i elicited by progesterone was entirely due to Ca2+ influx from the extracellular medium since the increase in [Ca2+]i was blocked by the Ca2+ chelator EGTA (2.5 mM) and the Ca2+ channel antagonist La3+ (0.25 mM) when added to the medium containing 2.5 mM Ca2+. Progesterone also stimulated the uptake of Mn2+ into sperm as measured by the quenching of fura 2 fluorescence. Progesterone has been found in human follicular fluid at levels capable of stimulating increases in [Ca2+]i. The similarities in responses induced by human follicular fluid and progesterone an increase in [Ca2+]i, and hence the acrosome reaction, is progesterone and/or 17 alpha-hydroxyprogesterone. Progesterone (1 microgram/ml) did not increase [Ca2+]i in somatic cells such as adipocytes, hepatocytes, Balb/c 3T3 cells, normal rat kidney, or DDT1 MF-2 cells. The effects of these progestins to increase [Ca2+]i, by activating a receptor-operated calcium channel, is the first report of such an activity in sperm. This phenomena possibly opens up a new field of steroid action in the area of sterility, fertility, and contraception at the level of the sperm. PMID- 2104841 TI - MK886, a potent and specific leukotriene biosynthesis inhibitor blocks and reverses the membrane association of 5-lipoxygenase in ionophore-challenged leukocytes. AB - Recently, we have shown that ionophore activation of human leukocytes results in leukotriene synthesis and a translocation of 5-lipoxygenase from the cytosol to cellular membrane. This membrane translocation was postulated to be an important early activation step for the enzyme. 3-[1-(p-Chlorobenzyl)-5-(isopropyl)-3-tert butylthioindol-2-yl]-2, 2- dimethylpropanoic acid (MK886) is a potent and specific inhibitor of leukotriene biosynthesis in vivo and in intact cells, but has no direct effect on 5-lipoxygenase activity in cell-free systems. In this report, we show that MK886 can both prevent and reverse the membrane translocation of 5-lipoxygenase, in conjunction with the inhibition of leukotriene synthesis. Similar compounds of the indole class could also inhibit the membrane translocation of 5-lipoxygenase in a rank order of potency that correlated with their potencies for leukotriene synthesis inhibition. In contrast L-656,224, a direct 5-lipoxygenase inhibitor, had no effect on the translocation of the enzyme. Attempts to demonstrate the effects of MK886 on the association of 5-lipoxygenase with membrane in cell-free preparations failed due to a nonspecific Ca2+-dependent sedimentation of the enzyme. The mechanism of action of MK-886 is therefore to block translocation, prevent subsequent activation of 5 lipoxygenase, and hence block cellular leukotriene biosynthesis. PMID- 2104842 TI - Occurrence of lipoxygenase products in membranes of rabbit reticulocytes. Evidence for a role of the reticulocyte lipoxygenase in the maturation of red cells. AB - A lipoxygenase has been found in the reticulocytes of all mammalian species tested so far (rabbit, rat, mouse, monkey, and humans); evidence from in vitro studies suggests that the lipid-peroxidizing effects of this enzyme could render the mitochondrion and other intracellular organelles prone to the proteolytic degradation which is a natural step in development of the reticulocyte to the mature red cell. In this study we sought evidence of an active lipoxygenase in vivo. A bleeding anemia was induced in rabbits, and in the course of the subsequent reticulocytosis the red cell membranes were examined for the presence of the characteristic lipoxygenase products of linoleic and arachidonic acids. Erythrocyte membranes from control collections contained only small amounts of hydroxy fatty acids (0.03-0.08% of the polyenoic fatty acids). In contrast, reticulocyte-enriched red cells contained up to 3.3% of the polyenoic acids as hydroxylated derivatives. The main hydroxy fatty acid in reticulocyte membranes was identified as 13-L(S)-hydroxy-9Z,11E-octadecadienoic acid. Small amounts of other hydroxy derivatives including 15-hydroxy-5,8,11,13 (Z,Z,Z,E)eicosatetraenoic acid were also detected. These products appeared about 3 days after development of reticulocytosis. The precise structures of the hydroxylated polyenoic fatty acids and the time course of their appearance strongly suggest that their formation is due to the intracellular action of the cell-specific reticulocyte lipoxygenase. These findings are the first evidence for an activity of this enzyme in vivo, and the results support the hypothesis that enzymic peroxidation of reticulocyte intracellular membranes is a step in preparation of the intracellular organelles for proteolytic degradation. PMID- 2104843 TI - Purification, characterization, and gene cloning of thermopsin, a thermostable acid protease from Sulfolobus acidocaldarius. AB - A thermostable, acid proteolytic activity has been found to be associated with the cells and in the culture medium of Sulfolobus acidocaldarius, an archaebacterium. This acid protease, which has been named thermopsin, was purified to homogeneity from the culture medium by a five-step procedure including column chromatographies on DEAE-Sepharose CL-6B, phenyl-Sepharose CL 4B, Sephadex G-100, monoQ (fast protein liquid chromatography), and gel filtration (high pressure liquid chromatography). The purified thermopsin produced a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the proteolytic activity was associated with the band. Thermopsin is a single-chain protein as indicated by gel electrophoresis and by a single NH2-terminal sequence. It has maximal proteolytic activity at pH 2 and 90 degrees C. A genomic library of S. acidocaldarius was prepared and screened by an oligonucleotide probe designed from the NH2-terminal sequence of thermopsin. Five positive clones were isolated. From these clones the thermopsin gene was mapped and sequenced. The nucleotide sequence showed that the thermopsin structure is encoded in 1020 bases. In the deduced protein sequence, there are 41 amino acid residues (including the initiation Met) preceding the NH2-terminal position of thermopsin. Most of these residues appear to be characteristic of a leader sequence. However, the presence in this region of a short pro sequence cannot be ruled out. Thermopsin contains a single cysteine at residue 237 that is not essential for activity (Fusek, M., Lin, X.-L., Tang, J. (1990) J. Biol. Chem. 265, 1496-1501. Thermopsin has no apparent sequence similarity to aspartic proteases of the pepsin family nor to pepstatin-insensitive acid protease (Maita, T., Nagata, S., Matsuda, G., Murata, S., Oda, K., Murao, S., and Tsura, D. (1984) J. Biochem. 95, 465-475) and thus may represent a new class of acid proteases. Also absent is the characteristic active site aspartyl sequence of aspartic proteases. There are 11 potential N-glycosylation sites on each thermopsin molecule. The molecular weight estimated from gel filtration (45,000) is larger than that calculated from the sequence (32,651), suggesting that thermopsin is the sequence (32,651), suggesting that thermopsin is glycosylated at at least some of these 11 sites. PMID- 2104844 TI - Enzymic properties of thermopsin. AB - The specificity of thermopsin, a thermostable acid protease from Sulfolobus acidocaldarius, was studied using oxidized insulin B chain as substrate followed by peptide isolation and identification. The following bonds were hydrolyzed: Leu Val, Leu-Tyr, Phe-Phe, Phe-Tyr, and Tyr-Thr. Thus, the specificity of thermopsin is similar to that of pepsin, that is, it prefers large hydrophobic residues at both sides of the scissile bond. We confirmed this by the use of a synthetic substrate, Lys-Pro-Ala-Glu-Phe-p-nitro-phenylalanyl-Ala-Leu, which was cleaved by thermopsin between Phe and p-nitro-phenylalanyl. Using this substrate, enzyme inhibition and kinetic properties of thermopsin have been studied. Thermopsin optimally hydrolyzes this substrate at 75 degrees C and pH 2 with Km and kcat values under these conditions of 5.3 x 10(-5) M and 14.3 s-1, respectively. Pepstatin competitively inhibits thermopsin with a Ki of 2 x 10(-7) M. Other known aspartic protease inhibitors, diazoacetylnorleucine ethyl ester and 1,2 epoxy-3-(p-nitrophenoxy)propane inhibited thermopsin only slowly and with nonspecific reactions. Although thermopsin contains a single cysteine, iodoacetic acid and p-chloromercuric benzoate had no effect on activity. Mercuric chloride inhibited the enzyme, and the inhibition was reversible by mercaptoethanol. However, the enzyme was not labeled by [14C]iodoacetic acid either before or after sodium dodecyl sulfate denaturation. Thus, the thiol group is likely blocked, and the inhibition effect of mercuric ion is unrelated to the thiol group. These observations suggest that thermopsin has a different active site than the aspartic protease family but may have a similar transition state structure. The temperature dependence of Km and kcat was studied for thermopsin hydrolysis of the synthetic substrate between 26-78 degrees C. Both parameters increased with temperature, and the rise of kcat value was particularly sharp above 65 degrees C. Hydrolysis activity measured at high substrate concentration has a maximum at 76 degrees C, which is near the physiological temperature for the optimal growth of this organism. Thus, thermopsin appears to function best at high temperature and high substrate concentration. It may be utilized by the organism to response to the presence of high substrate concentration in the medium. Thermopsin is also competitively inhibited by urea, acetamide, and phenylalaninamide with Ki values of 0.5, 0.4, and 0.01 M, respectively. PMID- 2104845 TI - Different members of the jun proto-oncogene family exhibit distinct patterns of expression in response to type beta transforming growth factor. AB - Type beta transforming growth factor (TGF-beta) is a multifunctional regulator of cell growth and differentiation. In the BC3H1 muscle cell line, TGF-beta blocks the onset of differentiation when added to undifferentiated myoblasts and causes dedifferentiation when added to fully differentiated myocytes. The goal of the present study was to determine whether TGF-beta-dependent repression of muscle specific genes was preceded by modulation in expression of members of the jun proto-oncogene family, which function as growth factor-inducible transcription factors. junB mRNA was expressed at a basal level in differentiated BC3H1 myocytes. Within 15 min following exposure of myocytes to TGF-beta, junB mRNA began to accumulate; a peak of expression 20-fold above basal levels was observed after 2 h with a gradual decline thereafter. Nuclear run-on transcription assays showed that induction of junB by TGF-beta occurred at the level of transcription through a mechanism independent of protein synthesis. junB was also induced by 20% fetal bovine serum, platelet-derived growth factor, and insulin, but the maximal level of expression in response to these growth factors was lower and less sustained than in the presence of TGF-beta. In contrast to the dramatic effects of TGF-beta on junB expression, c-jun showed only a 2.5-fold increase in expression in response to TGF-beta. In an effort to identify additional members of the jun family which might be regulated by TGF-beta, a cDNA library was prepared from the poly(A)+ mRNA of TGF-beta-stimulated BC3H1 myocytes and was screened under conditions of reduced stringency with a v-jun DNA probe. From this screen, a new jun-related gene product was identified which shared a high degree of homology with regions of c-jun and junB which have been implicated in transcriptional activation, dimerization, and DNA binding. The transcript for this jun-related gene was expressed constitutively in BC3H1 cells and was not regulated by TGF-beta. Three members of the jun family thus exhibit distinct responses to TGF-beta in BC3H1 cells. The rapid transcriptional induction of junB is among the earliest and most dramatic responses to TGF-beta yet described and suggests that junB may mediate certain of the diverse biological effects of this growth factor. PMID- 2104846 TI - Different kinetic properties of the two mutants, RAS2Ile152 and RAS2Val19, that suppress the CDC25 requirement in RAS/adenylate cyclase pathway in Saccharomyces cerevisiae. AB - The properties of RAS2Gly19----Val and RAS2Thr152----Ile, two mutants suppressing the CDC25 requirement for the activation of adenylate cyclase in Saccharomyces cerevisiae, were compared with the properties of wild-type RAS2. We examined (a) the guanine nucleotide interaction, (b) the intrinsic GTPase (EC 3.6.1-) activity, and (c) the ability to activate adenylate cyclase in vitro. The low GTPase of RAS2Val19 is associated with an increased stability of the GTP complex. By contrast, RAS2Ile152 shows a strong destabilization of the GDP complex (the dissociation rate constants of the RAS2Ile152.GDP complex is enhanced almost 50 times) and an increased GTPase activity. Remarkably, all the parameters of the interaction with GDP and GTP as well as the catalytic activity are modified by the two mutations in an opposite manner. Our kinetic results show that the functional modifications of RAS2 compensating for the CDC25 inactivation can not only be associated with the presence of a long-lived RAS2.GTP complex, but also with a rapid GDP to GTP exchange reaction. As a striking result, the functional modifications induced by Thr152----Ile activate the adenylate cyclase in vitro much more efficiently than those induced by Gly19----Val. This stresses the importance of a rapid regeneration of the RAS2.GTP complex for the activation of the adenylate cyclase pathway. PMID- 2104847 TI - Structural and functional characterization of a cell surface binding protein of vaccinia virus. AB - The nature of the interaction between the enveloped DNA-containing poxviruses and the surfaces of host cells as a first step in virus infection is not known. In this investigation we have identified and defined structural and functional properties of a 32-kDa protein of vaccinia virus. This protein is part of the virus envelope and binds to the cell surface of various cultured cells. The gene encoding the 32-kDa viral protein was mapped and sequenced. It was found to code a 35,426-Da protein with a large N-terminal domain with sequence homology to carbonic anhydrases and a C-terminal domain with sequences similar to those of the attachment glycoprotein VP7 of rotavirus and to transmembrane proteins. A potential cell surface binding domain was within the last 50 amino acid residues of the C terminus. The 32-kDa protein is basic, predicted pI 8.67, is synthesized at late times post-infection, may form dimers held by disulfide bonds at the single cysteine 262, and is apparently non-glycosylated. The 32-kDa protein is a vaccinia virus antigen, with predicted antigenic sites located near amino acids 108-110 (carbonic anhydrase domain) and 298-299 (transmembrane domain). Several lines of evidence suggest that the 32-kDa protein is needed for efficient virus replication in cultured cells but that in addition to this protein other viral proteins are involved in the process of virus entry into cells. PMID- 2104848 TI - Identification of the CBP1 polypeptide in mitochondrial extracts from Saccharomyces cerevisiae. AB - CBP1 is a nuclearly encoded yeast protein required for stability of mitochondrial cytochrome b pre-mRNA. Previous studies have shown that CBP1 stabilizes the cytochrome b transcripts via interaction with the 5'-end. For the present study, both rabbit polyclonal and mouse monoclonal antibodies against CBP1 were prepared using a trpE-CBP1 fusion polypeptide as a source of antigen. CBP1 was undetectable in a crude mitochondrial fraction from a wild-type strain by Western blot assay, but a 66-kDa immunoreactive protein was detected in a more purified fraction. The 66-kDa protein was absent in the equivalent fraction from a strain with a deletion in CBP1. Assignment of Mr = 66,000 to the mature CBP1 polypeptide was verified by Western analysis of mitochondria from a strain which over expresses CBP1. Mitochondrial localization was verified by transcribing CBP1 in vitro with T3 polymerase, translating the artificial mRNA in a rabbit reticulocyte system and importing 35S-CBP1 precursor polypeptides into isolated mitochondria. The mature protein product was 66 kDa, whereas the precursor protein migrated as if it were 68 kDa rather than 76 kDa as predicted from the sequence. Analysis of polypeptides truncated at the carboxyl terminus showed that CBP1 polypeptides migrate anomalously fast in the Laemmli system due to a property of the carboxyl two-thirds of the primary sequence, several sections of which are extremely basic. PMID- 2104849 TI - Synthesis of inactive nonsecretable high mannose-type lipoprotein lipase by cultured brown adipocytes of combined lipase-deficient cld/cld mice. AB - Combined lipase deficiency (cld) is a recessive mutation which causes a severe deficiency of lipoprotein lipase and hepatic lipase activities and lethal hypertriacylglycerolemia within 3 days in newborn mice. The effect of this genetic defect on lipoprotein lipase was studied in primary cultures of brown adipocytes derived from tissue of newborn mice. Cells cultured from cld/cld mice replicated, accumulated triacylglycerol, and differentiated into adipocytes at normal rates. Lipoprotein lipase activity in unaffected cells was detectable on Day 0 of confluence and increased to 1.3 units/mg DNA by Day 6, while that in cld/cld cells was less than 4% of that in unaffected cells on Days 4-6. Unaffected cells released 1.2% of their lipase activity in 30 min in the absence of heparin, and 11% in 10 min in the presence of heparin, whereas cld/cld cells released no lipase activity. cld/cld cells contained 2-3 times as much lipoprotein lipase protein as unaffected cells, and released no lipase protein to the medium. Immunofluorescent lipoprotein lipase was not detectable in unaffected adipocytes unless lipase secretion was blocked with monesin, causing retention of the lipase in Golgi. cld/cld adipocytes, in contrast, contained immunofluorescent lipoprotein lipase distributed in a diffuse reticular pattern, indicating retention of lipase in endoplasmic reticulum. Lipoprotein lipase immunoprecipitated from cells incubated 1-3 h with [35S]methionine was digested with or without endoglycosidase H (endo H) or F, and resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Lipoprotein lipase in unaffected cells (Mr = 56,000-58,000) consisted of three glycosylated forms, of which the most prevalent was endo H-resistant, the next was totally endo H-sensitive, and the least was partially endo H-sensitive. In contrast, lipoprotein lipase in cld/cld cells (Mr = 56,000) consisted of a single, totally endo H-sensitive form. Lipoprotein lipase in both groups of cells contained two oligosaccharide chains. Chromatography studies with heparin-Sepharose indicated that at least some of the lipoprotein lipase in cld/cld cells was dimerized. The findings demonstrate that brown adipocytes cultured from cld/cld mice synthesize lipoprotein lipase with two high mannose oligosaccharide chains, but it is inactive and retained in endoplasmic reticulum. Whether the cld mutation affects primarily processing of oligosaccharide chains of lipoprotein lipase in endoplasmic reticulum, transport of the lipase from the reticulum, or some other process, is to be resolved. PMID- 2104850 TI - Isolation and characterization of major urinary amino acid O-glycosides and a dipeptide O-glycoside from a new lysosomal storage disorder (Kanzaki disease). Excessive excretion of serine- and threonine-linked glycan in the patient urine. AB - Four major sialo compounds, termed GP-M1, GP-D1, GP-D2, and GP-D3 have been isolated from the urine of a novel glycoprotein storage disorder patient with angiokeratoma corporis diffusum which was discovered by Kanzaki et al. (Kanzaki, T., Yokota, M., Mizuno, N., Matsumoto, Y., and Hirabayashi, Y. (1989) Lancet April 22, 875-877). Based on the results of fast atom bombardment mass spectrometry, methylation analysis, and proton nuclear magnetic resonance spectroscopy, their chemical structures were concluded to be: (formula; see text) The yields of GP-M1, GP-D1, GP-D2, and GP-D3 were approximately 15, 6, 50, and 5 mg/liter of urine, respectively. The most major compound GP-D2, was further purified into single molecular species, threonine and serine type, by reversed phase high performance liquid chromatography. NMR analysis of the two purified compounds with single molecular species showed that the chemical shifts of anomeric protons of GalNAc were significantly different between threonine- and serine-linked GalNAc. Neither mannose-containing glycopeptides nor glycosphingolipids were excreted in the patient urine. From these results, this disease is thought to be caused by the deficiency of a lysosomal enzyme(s) acting on O-linked glycan chains. PMID- 2104851 TI - Purification and properties of a kinase from Escherichia coli K-12 that phosphorylates two periplasmic transport proteins. AB - The phosphorylation in vivo and in vitro of the arginine-ornithine and the lysine arginine-ornithine (LAO) periplasmic transport proteins of Escherichia coli K-12 was previously reported (Celis, R. T. F. (1984) Eur. J. Biochem. 145, 403-411). The phosphorylative reaction required ATP (as a direct energy donor), Mg2+, and a kinase that can be released by osmotic shock treatment of the cells. The enzyme was purified to electrophoretic homogeneity. The enzyme exhibited an ATPase activity and a kinase activity. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate gave an apparent molecular weight of 43,000 for the enzyme. The native protein showed the same molecular weight, suggesting that the protein is a monomer. The protein showed an apparent isoelectric point of 4.8 on isoelectric focusing. The two enzymatic reactions required a divalent cation and the apparent Km value for Mg2+ for the kinase activity was 0.5 mM. Mn2+ and Co2+ served as well as Mg2+, whereas Zn2+ and Ca2+ did not support activity. The ATPase activity of the enzyme yielded an apparent Km value for ATP of 50 microM. A similar value, Km of 100 microM, was calculated for the kinase activity with different concentrations of ATP. The enzyme showed a pH optimum of 7.3. PMID- 2104852 TI - Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution. AB - The three-dimensional structure of human erythrocytic purine nucleoside phosphorylase has been determined at 3.2 A resolution using x-ray diffraction data. Intensity data were measured using radiation from the Synchrotron Radiation Source, Daresbury, England, and oscillation film techniques. Phases were determined by using multiple isomorphous replacement methods with four heavy-atom derivatives and were improved using solvent flattening techniques. Purine nucleoside phosphorylase exists in the crystal as a trimer in which subunits are related by a crystallographic 3-fold axis. Each subunit contains an eight stranded mixed beta-sheet and a five-stranded mixed beta-sheet which join to form a distorted beta-barrel structure. This core beta-structure is flanked by seven alpha-helices in a manner that generates a novel folding pattern. The active site, which was characterized from binding of the substrate analogs 8-iodoguanine and 5'-iodoformycin B, is located near the subunit-subunit boundary within the trimer and involves seven different segments from one subunit and an additional short segment from an adjacent subunit. In the crystal, the phosphate-binding site is probably occupied by a sulfate ion. The specificity of purine nucleoside phosphorylase for guanine, hypoxanthine, and their analogs can be explained on the basis of the arrangement of hydrogen bond donors and acceptors in the active site. PMID- 2104853 TI - Prophylactic antimicrobial coverage in arthroplasty patients. PMID- 2104854 TI - Blood-gas and circulatory changes during total knee replacement. Role of the intramedullary alignment rod. AB - The use of an intramedullary alignment rod in the distal part of the femur is an important step in performing total knee-replacement arthroplasty. On the basis of our observation of a sudden decrease in oxygen saturation in some patients after insertion of the rod, a prospective study was done of the circulatory and blood gas changes that were associated with insertion in thirty-five patients. We examined the effects of the use of an eight-millimeter solid alignment rod, with and without venting; an eight-millimeter fluted alignment rod, with venting; and an eight-millimeter fluted or solid alignment rod, inserted through a 12.7 millimeter drill-hole, but without other venting. A statistically significant reduction in oxygen saturation, arterial oxygen tension (PaO2), and end-tidal carbon-dioxide tension (PETCO2) occurred after insertion of both solid and fluted eight-millimeter alignment rods through an eight-millimeter hold in both vented and unvented femoral canals, in association with a significant increase (p less than 0.01) in intramedullary pressure. Bone-marrow contents and fat were retrieved from samples of blood from the right atrium, indicating that embolization of marrow contents had occurred during insertion of the alignment rod. A small decrease in systemic blood pressure and heart rate also occurred. These changes were completely eliminated by the use of a 12.7-millimeter drill hole as the entry site of the eight-millimeter fluted rod. We concluded that insertion of an intramedullary alignment rod in the femur causes embolization of marrow contents, which decreases arterial oxygen tension, oxygen saturation, end tidal carbon-dioxide tension, arterial blood pressure, and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104855 TI - Calcaneonavicular coalition treated by resection and interposition of the extensor digitorum brevis muscle. AB - Seventy-five feet in forty-eight patients that had calcaneonavicular coalition were evaluated at two to twenty-three years after resection of the coalition and interposition of the extensor digitorum brevis muscle. The result was excellent or good in fifty-eight feet (77 per cent). Three feet that were rated initially as having a fair result improved over time, and at the last follow-up the result in those feet was rated as good. Only five feet (7 per cent) had a poor result. The best results were in patients who had a cartilaginous coalition and who were less than sixteen years old at the time of operation. PMID- 2104856 TI - The majority of type 1 plasminogen activator inhibitor associated with cultured human endothelial cells is located under the cells and is accessible to solution phase tissue-type plasminogen activator. AB - The interactions between exogenously added tissue-type plasminogen activator (t PA) and the active form of type 1 plasminogen activator inhibitor (PAI-1) produced by and present in cultured human umbilical vein endothelial cells (HUVECs) were investigated. Immunoblotting analysis of the conditioned media obtained from monolayers of HUVECs treated with increasing concentrations of t-PA (less than or equal to 10 micrograms/ml) revealed a dose-dependent formation of both t-PA/PAI-1 complexes, and of a 42,000-Mr cleaved or modified form of the inhibitor. Immunoradiometric assays indicated that t-PA treatment resulted in a fourfold increase in PAI-1 antigen present in the conditioned media. This increase did not result from the release of PAI-1 from intracellular stores, but rather reflected a t-PA-dependent decrease in the PAI-1 content of the Triton X 100 insoluble extracellular matrix (ECM). Although the rate of t-PA-mediated release of PAI-1 was increased by the removal of the monolayer, similar quantities of PAI-1 were removed in the presence or absence of the cells. These results suggest that the cells only represent a semipermeable barrier between ECM associated PAI-1 and exogenous t-PA. Treatment of HUVECs with t-PA (1 microgram/ml, 2 h) to deplete the ECM of PAI-1 did not affect the subsequent rate of PAI-1 production and deposition into the ECM. Immunogold electron microscopy of HUVECs not only confirmed the location of PAI-1 primarily in the region between the culture substratum and ventral cell surface but failed to demonstrate significant (less than 1%) PAI-1 on the cell surface. Thus, the majority of PAI-1 associated with cultured HUVEC monolayers is present under the cells in the ECM and is accessible to solution-phase t-PA. PMID- 2104859 TI - Airway hyperresponsiveness in asthma. AB - Some asthma triggers exert their major action through cellular inflammatory mechanisms, with resultant airway hyperreactivity to both allergenic and nonallergenic stimuli. Other triggers are simply bronchospastic, so that they do not increase vulnerability. Anti-inflammatory treatments are more important than purely bronchodilator therapy is for long-term control of asthma. PMID- 2104858 TI - Characterization of the collagen in the hexagonal lattice of Descemet's membrane: its relation to type VIII collagen. AB - To investigate the nature of the hexagonal lattice structure in Descemet's membrane, monoclonal antibodies were raised against a homogenate of bovine Descemet's membranes. They were screened by immunofluorescence microscopy to obtain antibodies that label Descement's membrane. Some monoclonal antibodies labeled both Descemet's membrane and fine filaments within the stroma. In electron microscopy, with immunogold labeling on a critical point dried specimen, the antibodies labeled the hexagonal lattices and long-spacing structures produced by the bovine corneal endothelial cells in culture; 6A2 antibodies labeled the nodes of the lattice and 9H3 antibodies labeled the sides of the lattice. These antibodies also labeled the hexagonal lattice of Descemet's membrane in situ in ultrathin frozen sectioning. In immunofluorescence, these antibodies stained the sclera, choroid, and optic nerve sheath and its septum. They also labeled the dura mater of the spinal cord, and the perichondrium of the tracheal cartilage. In immunoblotting, the antibodies recognized 64-kD collagenous peptides both in tissue culture and in Descemet's membrane in vivo. They also recognized 50-kD pepsin-resistant fragments from Descemet's membranes that are related to type VIII collagen. However, they did not react either in immunoblotting or in immunoprecipitation with medium of subconfluent cultures from which type VIII collagen had been obtained. The results are discussed with reference to the nature of type VIII collagen, which is currently under dispute. This lattice collagen may be a member of a novel class of long-spacing fibrils. PMID- 2104857 TI - Expression and function of chicken integrin beta 1 subunit and its cytoplasmic domain mutants in mouse NIH 3T3 cells. AB - Chicken integrin beta 1 cDNA and its site-directed mutants were cloned into a mammalian expression vector and introduced into mouse NIH 3T3 cells. Stable transfectants expressing the chicken beta 1 subunit or its site-directed mutants were identified by immunostaining with antibodies specific for the chicken integrin beta 1 subunit. The chicken beta 1 proteins were expressed predominately in the endoplasmic reticulum of transfectants and to a lesser degree in the plasma membrane. Immunoblots and immunoprecipitations, using anti-chicken integrin antibodies, revealed three different sizes of the chicken subunit (90, 95, and 120 kD) and a mouse 140-kD alpha subunit. Immunoprecipitations of the cell surface receptors showed only two peptides, an 120-kD beta 1 and an 140-kD alpha subunit. Antibodies perturbing mouse and chicken integrin-specific cell adhesions were used to demonstrate that the chimeric receptors functioned in adhesion to both laminin and fibronectin. Immunofluorescent staining with antibodies specific for either the chicken or mouse receptors showed that both the wild type and the chimeric receptors localized in focal contacts. Several mutations in the cytoplasmic domain were synthesized and used in the transfection experiments. In one mutant the tyrosine (Tyr 788) in the consensus sequence for phosphorylation was replaced by a phenylalanine. In another the lysine (Lys 757) at the end of the membrane spanning region was replaced by a leucine. Both of these mutants formed dimers with mouse alpha subunits, participated in adhesion, localized in focal contacts, and displayed biological properties indistinguishable from the wild-type transfection. In contrast, mutants containing deletions greater than 5-15 amino acids nearest the carboxyl end in the cytoplasmic domain neither promoted adhesion nor localized in focal contacts. They did, however, form heterodimers that were expressed on the cell surface. PMID- 2104860 TI - Intestinal development and regeneration. AB - This first article of a new series on "cellular" gastroenterology focuses on the embryogenesis and neonatal development of the gut. In this context, the effects of malnutrition, morbidity, and trauma on intestinal histodynamics are discussed, as are compensatory adaptations analogous to those in the circulatory responses to heart failure. PMID- 2104861 TI - To the Nobska lighthouse. PMID- 2104862 TI - Management of nonvariceal upper GI hemorrhage. AB - Peptic ulcer disease remains the most common upper GI hemorrhagic diathesis, except, of course, for esophageal varices. But mucosal lesions such as vascular ectasias and superficial ulcers of Dieulafoy's disease are being increasingly recognized. Therapeutic endoscopic techniques, notably laser coagulation and injection sclerotherapy, may obviate surgery. PMID- 2104863 TI - William Beaumont and the case of the fascinating fistula. PMID- 2104864 TI - Aerosolized insulin. PMID- 2104865 TI - An antivivisectionist on animal research. PMID- 2104866 TI - Xaos, Chaos chaos, and chaos. PMID- 2104867 TI - Diagnosis by fiat. PMID- 2104868 TI - An eight-year-old with recurrent pulmonary infections. PMID- 2104869 TI - Postoperative abdominal pain and diarrhea. PMID- 2104870 TI - Differential diagnosis of arm pain. PMID- 2104871 TI - Balloon valvuloplasty for aortic stenosis. AB - Balloon valvuloplasty has recently emerged as an option for elderly patients who are poor surgical candidates. With medical management the prognosis is dismal; definitive treatment is valve replacement. The new procedure provides hemodynamic and symptomatic relief, but there are major complications. Restenosis is common and mortality during follow-up remains high. PMID- 2104872 TI - Irregular tachycardia after cardiac surgery. PMID- 2104873 TI - 'Workup' for a bioethical problem. PMID- 2104874 TI - Current issues in diuretic therapy. PMID- 2104875 TI - Controversies in congestive heart failure therapy. PMID- 2104876 TI - Emergency room management of congestive heart failure. PMID- 2104877 TI - A low-fat diet decreases high density lipoprotein (HDL) cholesterol levels by decreasing HDL apolipoprotein transport rates. AB - Diets that reduce atherosclerosis risk lower levels of HDL cholesterol (HDL-C), but the significance of this is unclear. To better understand the mechanism of this phenomenon we studied the turnover of HDL apolipoproteins A-I and A-II in 13 subjects on two contrasting metabolic diets. Upon changing from high to low intake of saturated fat and cholesterol the mean HDL-C decreased 29% from 56 +/- 13 (SD) to 40 +/- 10 mg/dl, while apo A-I levels fell 23% from 139 +/- 22 to 107 +/- 22 mg/dl (both P less than 0.001). Mean apo A-II levels did not change. The fractional catabolic rate (FCR) of apo A-I increased 11% from 0.228 +/- 0.048 to 0.254 +/- 0.063 pools/d, while its absolute transport rate (TR) decreased 14% from 12.0 +/- 2.7 to 10.3 +/- 3.4 mg/kg per d (both P = 0.005). The decrease in HDL-C and apo A-I levels correlated with the decrease in apo A-I TR (r = 0.79 and 0.83, respectively; P less than 0.001), but not with the increase in apo A-I FCR (r = -0.04 and -0.02, respectively). In contrast, within each diet the HDL-C and apo A-I levels were inversely correlated with apo A-I FCR both on the high-fat (r = -0.85 and -0.77, P less than 0.001 and = 0.002, respectively) and low-fat diets (r = -0.67 and -0.48, P = 0.012 and 0.098, respectively) but not with apo A-I TR. In summary, diet-induced changes in HDL-C levels correlate with and may result from changes in apo A-I TR. In contrast, differences in HDL-C levels between people on a given diet correlate with and may result from differences in apo A-I FCR. Therefore, the mechanism of dietary effects on HDL levels differs substantially from the mechanism explaining the differences in levels between individuals on a fixed diet. In assessing coronary heart disease risk, it may be inappropriate to conclude that diet-induced decreases in HDL are equivalent to low HDL within a given diet. PMID- 2104878 TI - Interferon gamma drastically modifies the regulation of interleukin 1 genes by endotoxin in U937 cells. AB - IL-1 alpha, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) gene expression is induced by LPS (endotoxin) in monocytes/macrophages and in some monocytic cell lines. IFN gamma and 1 alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3) are important macrophage-activating factors. They induce changes in the human monocyte cell line U937 that reflect cellular differentiation. We have studied the effect of IFN-gamma and of 1,25(OH)2D3 on the expression of IL-1 and TNF alpha messenger RNA in response to LPS. The induction of these genes by LPS is immediate and transient, with a maximum in 3 h. Preincubation of the cells with IFN-gamma or with 1,25(OH)2D3 increases these mRNA responses to LPS about fourfold. More importantly, cells exposed to IFN-gamma for 72 h exhibit a drastically different and unexpected pattern of IL-1 alpha and IL-1 beta gene response to LPS. Instead of the normal transient response, one then observes a sustained increase in IL-1 alpha and IL-1 beta gene expression over at least 16 h after LPS stimulation. This was measured both at the level of mRNA and by direct transcription assays (run-off). This striking effect of IFN-gamma on the kinetics of IL-1 gene response does not apply to the TNF-alpha gene. Interestingly, 1,25(OH)2D3, which shares with IFN-gamma a number of important effects on monocytes/macrophages, does not affect the kinetics of IL-1 gene response to LPS. In view of the biological relevance of endotoxin as a macrophage activator, the potential clinical implication of this prolonged induction of IL-1 gene expression is discussed. PMID- 2104879 TI - Phagocytosis of Histoplasma capsulatum yeasts and microconidia by human cultured macrophages and alveolar macrophages. Cellular cytoskeleton requirement for attachment and ingestion. AB - Phagocytosis of Histoplasma capsulatum (Hc) yeasts and microconidia by human macrophages (M phi) was quantified by a fluorescence quenching technique. Phagocytosis of unopsonized Hc yeasts by monocyte-derived M phi and human alveolar M phi (AM) was rapid. After 60 min, 79% of cultured M phi and 59% of AM had ingested an average of 9.8 and 11 yeasts/M phi, respectively. In contrast, only 26% of monocytes ingested 4.5 yeasts/cell after 60 min. Phagocytosis of unopsonized microconidia by cultured M phi and by AM was equivalent. Monoclonal antibodies specific for the alpha-chains and beta-chain of the CD18 family of adhesion receptors inhibited the binding of Hc yeasts and microconidia to cultured M phi and AM. Thus, the M phi CD18 complex mediates recognition of both phases of this dimorphic fungus. Disruption of actin microfilaments with cytochalasin D inhibited both attachment and ingestion of yeasts by M phi. In contrast, nocodazole, which prevents polymerization of microtubules, did not inhibit binding or ingestion. Both drugs inhibited ingestion, but neither drug inhibited binding of C3b- and C3bi-coated sheep erythrocytes to complement receptors type one (CR1) or type three (CR3), respectively. Therefore, different signal transducing mechanisms for phagocytosis appear to be triggered by the binding of Hc yeasts to CD18, and by the binding of EC3bi to CD11b/CD18, respectively. PMID- 2104880 TI - Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein. AB - Neuropeptide Y (NPY) and peptide YY (PYY) are regulatory peptides that have considerable sequence homology with pancreatic polypeptide. Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells. In human fat cells NPY and PYY promoted a dose dependent inhibition of lipolysis elicited by 2 micrograms/ml adenosine deaminase (removal of adenosine) whatever the lipolytic index used (glycerol or nonesterified fatty acids). In dog fat cells NPY and PYY inhibited adenosine deaminase-, isoproterenol- and forskolin-induced lipolysis. In humans and dogs the effects of NPY or PYY were abolished by treatment of cells with Bordetella pertussis toxin, clearly indicating the involvement of a Gi protein in the antilipolytic effects. This study indicates that, in addition to alpha 2 adrenergic agonists, NPY and PYY are also involved in the regulation of lipolysis in human and dog adipose tissue as powerful antilipolytic agents. Further studies are needed to characterize the pharmacological nature of the receptor mediating the inhibitory effect of NPY and PYY in fat cells. PMID- 2104881 TI - Growth factor-dependent initiation of DNA replication in nuclei isolated from an interleukin 3-dependent murine myeloid cell line. AB - To study the proliferative response of hematopoietic cells to growth factors at the molecular level, we developed a cell-free system for growth factor-dependent initiation of genomic DNA replication. Nuclei were isolated from the IL-3 dependent cell line NFS/N1-H7 after a 10-h period of IL-3 deprivation. Cytosolic and membrane-containing subcellular fractions were prepared from proliferating NFS/N1-H7 cells. Nuclei from the nonproliferating cells (+/- IL-3) showed essentially no incorporation of [3H]thymidine during a 16-h incubation with a mixture of unlabeled GTP, ATP, UTP, CTP, dGTP, dATP, dCTP, and [3H]dTTP. When the combination of IL-3, a cytosolic fraction, and a membrane-containing fraction from proliferating cells was added to nuclei from nonproliferating cells, a burst of [3H]thymidine incorporation into DNA began after a 12-h lag period, attained a maximal rate at 16 h, and reached a level of 860 pmol thymidine/10(6) nuclei at 24 h (corresponding to replication of approximately 56% total mouse genomic DNA). This DNA synthesis was inhibited approximately 90% by the specific DNA polymerase alpha inhibitor aphidicolin. Deletion of a single cellular component or IL-3 from the system resulted in a marked reduction of DNA replication (-membrane, 80 +/- 4%; -cytosol, 90% +/- 4%; -IL-3, 74 +/- 7% inhibition). This model requires a growth factor (IL-3), a sedimentable cell fraction containing its receptor and possibly additional membrane-associated components, and a cytosolic fraction. It appears to recapitulate the molecular events required for progression from early G1 to S phase of the cell cycle induced by IL-3 binding to its receptor. PMID- 2104882 TI - Cermet cements. AB - Cermet ionomer cements are sintered metal/glass powders, which can be made to react with poly(acids). These new cements are significantly more resistant to abrasion than regular glass ionomer cements and are widely accepted as core build up materials and lining cements. They can strengthen teeth and provide the clinician with an opportunity to treat early dental caries. PMID- 2104883 TI - Glass ionomers for infants, children, and adolescents. AB - When practitioners fully understand the nature of the glass ionomer materials and use them within their limitations, their use can improve the quality of restorative dental care for young patients. The materials for young patients can be classified as luting cements, dentin replacement liners and bases, and glass ionomer dentin and enamel restorative material. Future research efforts should be directed toward improving the glass ionomer cement by increasing fracture toughness and wear resistance, decreasing hardening time, and simplifying the sensitive handling technique. PMID- 2104884 TI - The events surrounding the removal of encainide and flecainide from the Cardiac Arrhythmia Suppression Trial (CAST) and why CAST is continuing with moricizine. PMID- 2104885 TI - Successful treatment of age-related chorea with sodium valproate. PMID- 2104886 TI - Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. AB - The effect of cytokines on astrocytes cultured from mature bovine brain was determined both in a serum-containing medium and in a chemically-defined medium. The results showed that in serum-free medium, human TNF and, to a lesser degree, IL-6 and lymphotoxin, were mitogenic for astrocytes. Increased uptake of [3H]thymidine could be detected within 36 h in vitro and its presence in astrocytes was confirmed by autoradiography. In contrast, neither IL-1 alpha nor IL-1 beta induced astrocyte proliferation in serum-free medium but showed some synergistic effect with serum after 72 h. The proliferative effect of TNF and IL 6 was confirmed by cell counting. None of the cytokines tested was toxic for astrocytes as measured by 51Cr release. No mitogenic effect for oligodendroglia, purified from the same source, was detected. The results support a role for products of activated inflammatory cells in the development of astrocyte proliferation that may contribute to the reactive gliosis found in white matter diseases of the central nervous system such as multiple sclerosis. PMID- 2104887 TI - IL-1 secretion by macrophages. Enhancement of IL-1 secretion and processing by calcium ionophores. AB - In the present study we have demonstrated that the murine IL-1 alpha precursor lacks a cleavable signal sequence and does not undergo cotranslational translocation across microsomal membranes in vitro. Culture supernatants of the murine macrophage cell line, P388D, or from normal peritoneal macrophages collected within 0.5 to 3 h after stimulation contained the 33,000 m.w. precursor as the predominant form of IL-1 alpha. Over an 18-h period, the level of low m.w. IL-1 alpha increased as the secreted precursor was processed by extracellular and/or cell surface-associated proteolytic enzymes. The calcium ionophores A23187 and ionomycin were found to dramatically enhance the release and processing of murine and human IL-1. The rapid release of IL-1 in response to a change in the intracellular level of calcium does not appear to be caused by release of a membrane-bound form of the protein, nor is there evidence that IL-1 is packaged and released from cytoskeletal associated secretory granules. In marked contrast, calcium ionophores do not induce secretion of IL-1 from a nonmacrophage cell line that synthesizes but does not normally secrete IL-1. Our results suggest that activated macrophages possess a novel processing independent, possibly calcium dependent, mechanism that allows for the release of the precursor forms of IL-1 alpha and IL-1 beta. PMID- 2104888 TI - Alterations in the pattern of arachidonate metabolism accompany rat macrophage differentiation in the lung. AB - The present study was undertaken to investigate the changes in arachidonic acid (AA) metabolism which accompany rat macrophage (m phi) differentiation in the lung in order to determine whether these changes occur in the alveolar space or in the pulmonary interstitium, as well as the mechanisms responsible for such changes. Metabolism of endogenous and exogenous AA by cultured m phi obtained from the peritoneum (PM), the pulmonary interstitium (IM), and the alveolar spaces (AM) was examined by using HPLC and RIA. Although PM and AM released similar amounts of endogenous AA in response to both ionophore A23187 and the particulate zymosan, PM metabolized AA predominantly to cyclooxygenase (CO) products, whereas AM produced predominantly 5-lypoxygenase (5-LO) metabolites. IM synthesized a profile of eicosanoids which more closely resembled that of PM. Studies of the metabolism of exogenously supplied AA demonstrated that AM indeed had less CO activity than did PM. PM, but not AM, CO activity decreased during prolonged culture in air, suggesting the possibility that oxidative inactivation of CO plays a role in the decline in CO capacity which accompanies m phi differentiation in the lung. In contrast, the greater expression of 5-LO metabolism in AM than PM did not reflect mere differences in enzyme capacity, since upon activation of protein kinase C with PMA or oleoylacetylglycerol, ionophore-stimulated PM produced amounts of 5-LO products which were comparable to the amounts produced by AM stimulated with A23187 alone. These results indicate that increases in 5-LO metabolism and decreases in CO metabolism accompany rat m phi differentiation in the lung, that these changes occur largely in the alveolar space, and that the increased 5-LO capacity and decreased CO capacity are independently regulated by different mechanisms. PMID- 2104889 TI - Activated macrophages destroy intracellular Leishmania major amastigotes by an L arginine-dependent killing mechanism. AB - Macrophages infected with amastigotes of Leishmania major and treated with IFN gamma in vitro develop potent antimicrobial activities that eliminate the intracellular parasite. This antileishmanial activity was suppressed in a dose dependent fashion by NG-monomethyl-L-arginine (NGMMLA), a competitive inhibitor of nitrite, nitrate, nitric oxide and L-citrulline synthesis from L-arginine. Excess L-arginine added to infected macrophage cultures reversed the inhibitory effects of NGMMLA. Addition of arginase to culture media inhibited intracellular killing by IFN-gamma-treated cells. Similar effects were seen with macrophages obtained from BCG-infected C3H/HeN mice. Increased levels of nitrite, an oxidative product of the L-arginine-dependent effector mechanism, was measured in cultures of infected IFN gamma-treated macrophages as well as infected BCG activated macrophages. Nitrite production correlated with development of antileishmanial activity. Nitrite production and microbicidal activity both decreased when in vivo or in vitro-activated macrophages were cultured in the presence of either arginase or NGMMLA. Nitric oxide synthesized from a terminal guanidino nitrogen atom of L-arginine and a precursor of the nitrite measured, may disrupt Fe-dependent enzymatic pathways vital to the survival of amastigotes within macrophages. PMID- 2104890 TI - Alternate splice sites within the human VH gene coding sequences lead to truncated Ig mu-chains. AB - The Burkitt's lymphoma cell lines JBL2 and Ly91 contain intracytoplasmic mu chains without L chain by immunofluorescence. These mu chains and the corresponding cDNA are abnormally short. Detailed analysis of the productive H chain alleles showed that the cell lines JBL2 and Ly91 use a VHIV and a VHIII subgroup gene, respectively. In both cell lines, the 3' part of the V exon was markedly abnormal and contained several stop codons. Point mutations affected the JH6 donor splice site in the JBL2 gene, precluding normal splicing into C mu. Although the JH2 splice site was unmodified in Ly91, it was not used. As in JBL2, splicing occurred at an alternate splice site present 5' of these alterations, thus removing all these abnormalities from the mature transcripts. This alternate splicing explains the presence in both cell lines of truncated mRNA and proteins lacking two-thirds of the V region. PMID- 2104891 TI - Patterns and extent of isotype-specificity in the murine H chain switch DNA rearrangement. AB - We have analyzed the configuration of the H chain locus of 41 hybridomas by Southern blot analysis. Each H chain switch region was determined to be germ line, rearranged, or deleted. Including 13 previously analyzed hybridomas, 60% of those with rearrangements on both alleles showed a correlation of the two alleles, i.e., both the expressed and the nonexpressed alleles have rearranged to the same H chain constant region gene segment. When the two H chain alleles did not rearrange to the same gene, they often rearranged to neighboring H chain genes. These results support a role for isotype-specific factors in H chain switch recombination. The action of these isotype-specific factors may be propagated to some extent along the chromosome, which would lead to rearrangements to neighboring genes. PMID- 2104892 TI - Lymphokine-activated killer (LAK) cells. IV. Characterization of murine LAK effector subpopulations. AB - The precursors of murine lymphokine-activated killers (LAK) can be divided into two major subsets: NK-like (CD8-, NK1.1+, asialo GM1+) and T-like (CD8+, NK1.1-, asialo GM1+). LAK effectors have generally been characterized as being either CD8+ or NK1.1+. In this study, we divided each of these effector subsets further by virtue of their expression of B220 (as defined by the mAb 6B2) and Ly-24 (Pgp 1). Freshly obtained CD8+ and NK1.1+ cells were found, by fluorescence analysis, to be B220-. Lytically active LAK effector subsets were either CD8+ B220+ Ly-24+ or NK1.1+ B220+ Ly-24+. Most interestingly, a distinct NK1.1+ B220- Ly-24+ subset existed but had minimal lytic activity, suggesting that only a subset of NK cells is capable of acquiring the broad lytic activity of LAK. The acquisition of the B220 marker by the CD8+ subset closely paralleled its expression of lytic activity. However, classical MHC-restricted CD8+ CTL were Ly-24+ but remained B220- suggesting that the acquisition of the B220 marker, as defined by the 6B2 mAb, is not merely the result of cellular differentiation but may serve as a marker of MHC-nonrestricted killers. Three "classes" of target cells were examined for their susceptibility to lysis by the LAK effector subsets: YAC-1 (NK sensitive), CL27A (NK resistant), and autologous lymphoblasts that have been modified with 2, 4, 6-trinitrobenzene sulfonic acid. YAC-1 was lysed exclusively by the NK1.1+ B220+ Ly-24+ subset, 2,4,6-trinitrobenzene sulfonic acid-self was lysed exclusively by the CD8+ B220+ Ly-24+ subset whereas CL27A was lysed by both subsets. This pattern of lysis was confirmed by the in vivo depletion of NK1.1+ cells. It, therefore, appears that LAK effector subsets may be more selective in their lytic repertoire than previously thought. PMID- 2104893 TI - Clonal diversity in human B cell lymphoma. I. Idiotypic and genetic analysis of lymphoma heterohybrids. AB - Secretory heterohybrid clones from seven pristine human B cell lymphomas of diverse histologic types were established to investigate the question of tumor clonal diversity. We found that in six tumors, heterohybrid-derived Ig showed similar band patterns in IEF; families of anti-Id prepared from tumor Ig reacted uniformly with individual heterohybrids and original tumor; and the V gene loci displayed little variation on Southern analysis. In one patient who was followed with serial multiple site biopsies over a 14-mo period, clonal Id was preserved until the final stage of his disease, in spite of cytotoxic treatment. In a single follicular tumor (J.M.), each of the anti-Id reacted uniformly with the parent tumor and the individual heterohybrids, except that three of six clones failed to react with a single anti-Id family member. A Southern analysis of the VH gene locus revealed an identical gene rearrangement that was shared by the parent tumor and each heterohybrid. However, there was considerable heterogeneity of J.M. heterohybrid Ig in IEF gels, and we demonstrated the production of variant lambda L chains by the heterohybrid clones. One type of lambda L chain had a normal mobility in SDS-PAGE gels but larger lambda variants were produced by four of six heterohybrids. A Southern analysis of the VL gene displayed considerable variation in the type of lambda rearrangement present in the various heterohybrids, suggesting extensive diversity at the VL gene locus. In a second tumor (S.C.) that exhibited uniform anti-Id tumor reactivity we were also able to demonstrate the presence of a second minor tumor cell population (a biclonal tumor). Our data suggest that intraclonal VH variation may vary considerably with lymphoma subtype and mutagenic exposure and that an additional mechanism for generating spontaneous intraclonal heterogeneity is genetic variation at the VL locus. PMID- 2104894 TI - Immunosuppression and lymphoid hypoplasia associated with chronic graft versus host disease is dependent upon IFN-gamma production. AB - We have previously shown that both IFN-gamma and IFN-beta are produced in vivo and in vitro by spleen cells obtained from mice experiencing a chronic form of graft vs host disease (GVHD). Further, we have shown that in vitro production of IFN-beta by spleen cells from GVHD mice may play a role in the suppressed in vitro mitogen responsiveness of these cells. This study was undertaken to investigate if treatment of such mice with mAb to IFN-gamma or IFN-beta could alter the immunosuppression or lymphoid hypoplasia associated with chronic GVHD. GVHD was induced across minor histocompatibilities by the i.v. injection of B10.D2 spleen cells into sublethally irradiated BALB/c mice. These mice were given daily injections for 20 days of one of the following: 1) mAb to IFN-gamma, 2) mAb to IFN-beta, or 3) control IgG. Histologic examination of these mice at 21 to 22 days post transplantation revealed that mice treated with mAb to IFN-beta or control IgG had dramatic hypoplasia of the thymus, spleen, and lymph nodes which was similar to untreated GVHD mice. Mice given mAb to IFN-gamma, however, had no lymphoid hypoplasia and had a near normal gross and histologic appearance of their thymus, spleen, and lymph node tissue when compared with syngeneic controls. In vitro mitogen-induced proliferative responses of spleen and lymph node cells obtained from GVHD mice or GVHD mice treated with mAb to IFN-beta were severely suppressed or absent. In contrast, spleen and lymph node cells from GVHD mice given mAb to IFN-gamma were capable of giving a significant in vitro proliferative response to Con A, PHA, and LPS. Further, natural suppressor cell activity and spontaneous production of IFN-beta, a characteristic of this form of GVHD, was absent in spleen cells obtained from GVHD mice treated with mAb to IFN gamma. These results further identify the IFN as playing critical roles in the pathogenesis of GVHD. PMID- 2104895 TI - Mechanisms of deoxyguanosine lymphotoxicity. Human thymocytes, but not peripheral blood lymphocytes accumulate deoxy-GTP in conditions simulating purine nucleoside phosphorylase deficiency. AB - This study was designed to simulate purine nucleoside phosphorylase (PNP) deficiency by preincubating with guanosine (Guo) to minimize PNP activity while investigating the metabolism of [14C] deoxyguanosine (dGuo) at physiologic concentrations (10 microM) by unstimulated thymocytes, tonsil-derived T and B lymphocytes, and peripheral blood cells over short time periods. GTP was the principal metabolite formed from dGuo by all cell types with functional PNP and hypoxanthine-guanine phosphoribosyltransferase, confirming formation via degradation to guanine with subsequent salvage by hypoxanthine-guanine phosphoribosyltransferase. Thymocytes also formed a small amount of deoxyguanosine triphosphate (dGTP), presumably through direct phosphorylation by deoxycytidine kinase. Incorporation of dGuo into GTP was effectively inhibited in all instances under PNP deficiency conditions and dGTP levels increased up to 10 fold in thymocytes, but tonsil-derived B or T lymphocytes and unfractionated PBL still accumulated no detectable dGTP. E and platelets formed low amounts of dGTP under these conditions. Preincubation with adenine (50 microM) to reverse any Guo induced toxicity reduced the incorporation of dGuo into GTP without inhibitor in all cell types with intact adenine phosphoribosyltransferase, but had no effect on dGTP accumulation in thymocytes, with or without inhibitor, thus excluding any indirect formation of dGTP via the de novo route. The rapid metabolism of dGuo to GTP, in the absence of PNP inhibition and subsequent effects of the altered GTP concentrations on cellular metabolism, may account for the differing responses reported by investigators with the use of low dGuo concentrations (enhancing), compared with high (inhibitory), concentrations in mitogen-stimulated lymphocyte studies. The exclusive ability of thymocytes to accumulate significant amounts of dGTP, and inability of B cells to do so, provides a logical explanation for the selective T cell immunodeficiency in PNP deficiency. PMID- 2104896 TI - IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. AB - IL-6 is a regulator of inflammatory and immunological processes and high levels of this cytokine have recently been shown to be present in synovial fluids from inflammatory and degenerative arthropathies. Synovial fluid IL-6 may in part be a product of synoviocytes that have previously been identified as a source of IL-6. To further define intraarticular sources of IL-6, we examined the ability of chondrocytes to produce IL-6 and studied its modulation by inflammatory cytokines and homeostatic regulators of chondrocyte function. Human articular chondrocytes isolated from normal and osteoarthritic joints released low levels of IL-6 when cultured in the presence of serum. The inflammatory cytokines IL-1, and, to a lesser extent, TNF-alpha and IFN-gamma increased IL-6 production. Among the growth factors known to act on chondrocytes, only transforming growth factor beta, but not epidermal growth factor. fibroblast growth factor, insulin growth factor-1 and 2, platelet growth factor or insulin, was able to significantly increase IL-6 synthesis. Analysis of hormonal influences on chondrocyte IL-6 production showed that testosterone and estradiol synergized with IL-1 in the induction of IL-6. Hydrocortisone, at 10 ng/ml, reduced IL-1-induced IL-6 production by more than 50%. Chondrocyte-derived IL-6 stimulated acute phase protein synthesis and hybridoma cell proliferation. These biological activities were neutralized by a specific antibody to IL-6. Metabolic labeling and immunoprecipitation studies showed that IL-1 induced de novo synthesis of IL-6 and that the IL-6 proteins secreted by chondrocytes were similar to those from fibroblasts. These results demonstrate that chondrocytes are able to produce IL-6 in response to physiologic and inflammatory stimuli. Chondrocytes probably contribute to the increased synovial fluid levels of IL-6 in inflammatory and degenerative conditions of cartilage, and IL-6 may serve as a mediator to coordinate responses to cartilage injury. PMID- 2104897 TI - MHC regulation in neural cells. Distribution of peripheral and internal beta 2 microglobulin and class I molecules in human neuroblastoma cell lines. AB - mAb were used in an immunocytochemical assay to examine beta 2-microglobulin (b2 m) and class I MHC expression in human neuroblastoma cell lines. In lines with weak class I expression among the whole population, under ordinary assay conditions, strong b2-m and class I expression were concentrated in a small subpopulation. In positive cells, Ag was not restricted to any part of the cell body or processes. Strong expression was not required for establishment of any morphologic form or any type of cell contact. These findings complement studies in other experimental systems, where a nonimmunologic role for class I or b2-m in neural cell growth was not revealed. When the microscopic assay was modified to reveal Ag within the internal membrane system, b2-m was detected in every neuroblastoma cell. Most often, the Ag appeared as a ring around the nucleus, or in a punctate distribution in the juxtanuclear area. Internal expression of HLA chains and class I molecules was more difficult to detect, possibly reflecting a normal excess of b2-m. These findings increase understanding of MHC regulation in neural cell lines. They provide the technical and conceptual background for examination of internal MHC Ag in neural tissue. PMID- 2104898 TI - Anti-proliferative effect of IFN-gamma in immune regulation. IV. Murine CTL clones produce IL-3 and GM-CSF, the activity of which is masked by the inhibitory action of secreted IFN-gamma. AB - We have demonstrated recently that rIFN-gamma inhibits the proliferation of murine bone marrow cells stimulated with rIL-3 or recombinant granulocyte macrophage (GM)-CSF. In light of this finding, three murine CD8+ CTL clones whose supernatants had been shown previously not to contain detectable levels of CSF activity but which contained a relatively high level of IFN-gamma were reassessed for their ability to secrete IL-3 and GM-CSF. Supernatants from CTL clones activated with anti-CD3 mAb failed to stimulate the IL-3-dependent cell line FDCP1. However, these supernatants were indeed able to stimulate the proliferation of FDCP1 cells if anti-IFN-gamma mAb was present. This stimulatory activity was specifically neutralized by anti-IL-3 mAb. Supernatants from two of the three clones stimulated the proliferation of a GM-CSF-responsive HT-2 cell line, and this activity was neutralized by anti-GM-CSF antibody. The otherwise modest ability of CTL supernatants to stimulate the proliferation of fresh bone marrow cells was augmented considerably in the presence of anti-IFN-gamma mAb, and this activity was appropriately blocked by anti-IL-3 and anti-GM-CSF antibodies. mRNA for IL-3 and GM-CSF, as well as for IFN-gamma and TNF-alpha, was detected in cells that secreted those lymphokines, and the time course of appearance of each mRNA correlated with secretion of the appropriate lymphokine activity. However, the time course of mRNA accumulation for each lymphokine was distinct, the order of expression of these genes apparently being TNF-alpha, then IFN-gamma and GM-CSF, and finally IL-3. Our results emphasize that potential interactions among lymphokines must be considered when interpreting data obtained from lymphokine bioassays and suggest an immunoregulatory role for CTL through the secretion of several of the same lymphokines produced by HTL. PMID- 2104899 TI - A monoclonal antibody reactive with a 15-kDa cytoplasmic granule-associated protein defines a subpopulation of CD8+ T lymphocytes. AB - We have recently described a novel method for the production and characterization of mAb reactive with T cell-restricted intracellular antigens. From a panel of antibodies that react specifically with permeabilized T lymphocytes but not with permeabilized B lymphocytes or native T cells, we have selected one, designated TIA-1, that reacts with 20 to 36% of digitonin permeabilized peripheral blood T lymphocytes. Flow cytometric analysis of purified CD4+ and CD8+ subsets showed TIA-1 to recognize a subpopulation of 49 to 64% of CD8+ lymphocytes. Little or no reactivity with CD4+ resting T lymphocytes was observed. TIA-1 did not react with any of a panel of T cell lines, B cell lines, or monocytoid cell lines. TIA-1 reacted strongly with NK cell clones and CD8+ cytolytic T cell clones, and less strongly with CD4+-activated T cell clones, suggesting a preferential expression in cells possessing cytolytic potential. Cell fractionation experiments showed TIA-1 to be membrane associated. Furthermore, Percoll gradient fractionation of a cytolytic T cell clone (T4T8C1) showed the majority of TIA-1 to be contained in a low density membrane fraction that also contained serine protease activity. Immunoelectron microscopy showed TIA-1 to decorate the membranes of electron lucent and electron dense cytoplasmic granules in this same cytolytic T cell clone. Biochemical analysis showed TIA-1 to be a 15-kDa protein in unstimulated T cells. Upon activation with Con A or anti-CD3 antibodies. TIA-1 was induced to form disulfide linked dimers, trimers, and tetramers of the basic 15-kDa unit. Taken together, our data suggest that TIA-1 is a cytolytic granule associated protein that may define a subpopulation of resting CD8+ T lymphocytes possessing cytolytic potential. PMID- 2104900 TI - A molecular and structural analysis of the VH and VK regions of monoclonal antibodies bearing the A48 regulatory idiotype. AB - The results presented in this paper explore the molecular basis for expression of the A48 regulatory Id (RI). A48 RI+ mAb derived from idiotypically manipulated mice molecularly resembled the A48 and UPC 10 prototypes of this system by utilizing a VHX24-Vk10 combination. Id expression by these antibodies was not restricted by a particular D region sequence, JH, or JK segment, but quantitative differences in Id expression were associated with utilization of different members of the VK10 germ-line gene families. The VL sequences of these A48 RI+ mAb has identified amino acid residues lying in four different idiotope determining regions which may contribute to the structural correlate of this Id. A comparative sequence analysis of the VH regions of these VHX24 utilizing A48 RI+ mAb with several A48 RI+ mAb utilizing VHJ558 or VH7183 VH genes as well as a hybrid transfectoma antibody derived from two A48 RI-, VHJ558 utilizing hybridomas, all suggested that four nonconsecutive positions which lie outside the idiotope-determining regions may contribute structural elements toward expression of this Id. The VH and VL regions of the A48RI+, VHX24-Vk 10+ mAb showed low to moderate levels of somatic mutation which showed different patterns of distribution between the complementary determining region (CDR) and framework regions in the H and L chains. Although the VK sequences contained 50% of the replacement mutations in the CDR, with a replacement/silent mutation ratio of 10, the CDR of the VH sequences contained only 31% of the replacement mutations with a replacement/silent mutation ratio of 0.69. PMID- 2104901 TI - Regulatory effect of cytokines on eosinophil degranulation. AB - We tested the effects of different cytokines on IgA- and IgG-induced eosinophil degranulation in vitro to determine the potential interaction between eosinophils and mononuclear cells. Purified normodense eosinophils were incubated with cytokines (including rIL-1, rIL-2, rIL-3, rIL-4, rIL-5, rIL-6, IFN-gamma, granulocyte-macrophage CSF stimulating factor (GM-CSF), and TNF) for 1 to 3 h after which Ig-coupled Sepharose 4B beads were added as targets and the mixtures were incubated with the eosinophils at 37 degrees C for 4 h. The Ig used were secretory IgA (sIgA), serum IgA and IgG, and myeloma IgA and IgG. The release of eosinophil-derived neurotoxin (EDN) was measured by RIA as an index of degranulation. rIL-5 was the most potent enhancer of Ig-induced degranulation and increased EDN release by 48% for sIgA and 136% for IgG. The effect of rIL-5 appeared as quickly as 15 min after incubation of eosinophils, sIgA beads and IL 5. GM-CSF and rIL-3 also enhanced Ig-induced EDN release but less potently than rIL-5. GM-CSF and rIL-5 by themselves induced a small but significant release of EDN from eosinophils in the absence of Ig-coated beads; rIL-3 did not. However, IFN-gamma suppressed sIgA-induced EDN release by 23%. The other cytokines did not have any effect on eosinophil degranulation. These results suggest that cytokines which induce eosinophil differentiation and proliferation during hematopoiesis also enhance the effector function of mature eosinophils and that IFN-gamma partially down-regulates eosinophil degranulation. PMID- 2104902 TI - IL-2 can enhance the cyclosporin A-mediated inhibition of Theileria parva infected T cell proliferation. AB - The effect of cyclosporin A on the continuous proliferation of Theileria parva infected T cells was tested and compared with its effect on the Con A-induced proliferation of bovine lymph node cells. The effect of rIL-2 on cyclosporin A treated cells was also tested. Whereas the Con A-induced proliferation of bovine lymph node cells was completely inhibited by cyclosporin A, the continuous growth of T. parva-infected cells was only partly inhibited. In both cases the inhibition was accompanied by a reduction in the level of IL-2R/Tac mRNA and surface IL-2R expression. The cyclosporin A-mediated inhibition of Con-A stimulated lymphoblasts was, over a period of 5 days, largely abrogated by human rIL-2. In the short term, rIL-2 could also alleviate the growth inhibition of T. parva-infected cells caused by treatment with cyclosporin A. In the long term, however, rIL-2 enhanced the cyclosporin A-mediated inhibition of T. parva infected cells, gradually leading to their complete growth arrest. This enhanced inhibition was accompanied by a further reduction in surface IL-2R expression, but not by a further decrease in the levels of steady state IL-2R/Tac mRNA. The fact that IL-2 can enhance the inhibition caused by cyclosporin A could be of relevance for the immunosuppressive activity of cyclosporin A. PMID- 2104903 TI - Depletion of CD8+ T cells increases susceptibility and reverses vaccine-induced immunity in mice infected with Trypanosoma cruzi. AB - The role of CD8+ T cells in immune control of Trypanosoma cruzi infection in mice was examined by using in vivo depletion of CD8+ T cells with antibodies. Both the resistant C57BL/6J and the highly susceptible C3H/HeSnJ developed higher parasitemias and increased or earlier mortality when depleted of CD8+ T cells before infection with the Brazil strain of T. cruzi. CD8 depletion also affected the induction and expression of immunity to T. cruzi after vaccination with the avirulent Corpus Christi strain of T. cruzi. C57BL/6J mice depleted of CD8+ T cells either before or after vaccination showed a near total loss of vaccine induced protection. C3H mice were only partially protected by the vaccination procedure but the protection was totally reversed by anti-CD8 treatment. Chronically infected mice that had survived the acute infection were unaffected by CD8 depletion and showed neither a recrudescence of parasitemia nor an increased susceptibility to reinfection. These results suggest that CD8+ T cells play a role in immunity to T. cruzi in the acute phase but possibly not during the chronic phase of infection. Also, immunization with Corpus Christi strain T. cruzi induces an immunity that is distinct from that induced by survival of the acute phase of infection. The mechanism by which CD8+ T cells contribute to control of T. cruzi infection is not known. However, CD8 depletion had no effect on suppressed immune responses, suggesting their function in T. cruzi-infected mice is related more to the cytotoxic activity or cytokine-producing capacity of this subpopulation of T cells. PMID- 2104904 TI - Identification of enhancer-like elements in human IFN-gamma genomic DNA. AB - We have previously shown that transfection of a plasmid clone containing full length human IFN-gamma genomic DNA into a murine T-lymphoblastoid line is followed by basal expression of the transfected gene, with increased transcription occurring upon stimulation of the cells with either phorbol ester or IL-2. In addition, upon transfection of this DNA into murine fibroblasts, high level constitutive transcription was observed. In contrast to the results obtained under tissue culture conditions, introduction of the same DNA into the mouse germline resulted in tissue-specific expression of the transgene. We now report identification of a region 500-bp 5' of the human IFN-gamma TATAA box that has strong, PMA-inducible, enhancer-like activity when linked to a reporter gene (CAT) and transfected into a murine T cell line. However, when the same region of IFN-gamma genomic DNA was introduced into NIH-3T3 cells, no enhancer activity was detected either in the presence or absence of PMA. We have further found that an intronic region of the IFN-gamma genomic DNA (nucleotides 405-674) also contains enhancer activity that is functional in either fibroblasts or T cells. Enhancer activity of the intronic region is also PMA-inducible in the mouse T cells but constitutive in fibroblasts. Collectively, our observations suggest that control of human IFN-gamma gene expression is complex, involving noncontiguous regulatory domains in both 5' flanking and intronic regions of that gene. PMID- 2104905 TI - Coordinate expression of src family protooncogenes in T cell activation and its modulation by cyclosporine. AB - Activation of T lymphocytes induces transcription of several important genes which encode lymphokines and lymphokine receptors as well as "proliferation complementary" protooncogenes like c-myc or c-fos. Recently, the expression of lck gene, one of the src family gene, has also been shown to be modulated during T cell activation. We, therefore, assessed the question of whether other src family genes are expressed during the activation of T cells and of whether cyclosporine, a potent immunosuppressive drug, affects expression of these genes. We examined the expression of four different src family genes (lck, c-src, fyn, and c-fgr) in addition to the expression of IL-2, c-fos, c-myc, and actin genes in murine T cells which were activated with PMA plus ionomycin or PMA plus anti CD3 mAb. We found that T cell activation was associated with the up-regulation of these src family genes and that the expression of these genes was specifically blocked in the presence of cyclosporine indicating that these activation-related genes were coordinately regulated. PMID- 2104906 TI - Identification and characterization of monoclonal antibodies specific for macrophages at intermediate stages in the tumoricidal activation pathway. AB - Macrophage activation for tumor cell killing is a multistep pathway in which responsive macrophages interact sequentially with priming and triggering stimuli in the acquisition of full tumoricidal activity. A number of mediators have been identified which have activating capability, including in particular IFN-gamma and bacterial LPS. Although the synergistic functional response of normal macrophages to sequential incubation with these activation signals has been well established, characterization of the intermediate stages in the activation pathway has been difficult. We have developed a model system for examination of various aspects of macrophage activation, through the use of the murine macrophage tumor cell line, RAW 264.7. These cells, like normal macrophages, exhibit a strict requirement for interaction with both IFN-gamma and LPS in the development of tumor cytolytic activity. In addition, these cells can be stably primed by the administration of gamma-radiation. In the studies reported here, we have used RAW 264.7 cells treated with IFN-gamma alone or with IFN-gamma plus LPS to stimulate the production of rat mAb probes recognizing cell surface changes occurring during the activation process. In this way we have identified three Ag associated with intermediate stages of the activation process. One Ag, TM-1, is expressed on RAW 264.7 cells primed by IFN-gamma or gamma-radiation. This surface Ag thus identifies cells at the primed cell intermediate stage of the tumoricidal activation pathway regardless of the mechanism of activation. A second Ag, TM-2, is expressed on IFN-treated RAW 264.7 cells but not on RAW 264.7 cells primed with gamma-radiation alone. Expression of this Ag can be induced by treatment of irradiated cells with IFN-gamma, but is not induced by IFN-gamma treatment of a noncytolytic cell line, WEHI-3. This Ag thus appears to be an IFN-inducible cell surface protein associated specifically with macrophage activation for tumoricidal activity. Finally, Ag TM-3 is detectable on RAW 264.7 cells primed by either IFN-gamma or gamma-radiation, after subsequent triggering of the primed cells with LPS. The addition of the mAb recognizing this antigen to the function assay of tumor cell killing can inhibit they lytic activity of both triggered cells. Thus, this Ag may play a role in the antitumor effector functions of activated macrophages. Overall, the results suggest that these mAb can serve as useful tools for identification of molecules associated with the process of macrophage activation for tumor cell killing. PMID- 2104907 TI - A membrane-associated form of C-reactive protein is the galactose-specific particle receptor on rat liver macrophages. AB - Rat liver macrophages express a galactose-specific receptor which mediates endocytosis of particles or neuraminidase-treated blood cells. From rat serum we now have isolated and purified a galactose-specific lectin by affinity chromatography. Comparative analysis of this serum galactose-binding protein with the galactose-particle receptor protein purified from rat liver macrophages and with C-reactive protein (CRP) reveals close relation or identity of these proteins. An apparent m.w. of 30,000 was determined for all three proteins by SDS PAGE under reducing conditions and m.w. of about 130,000 by native PAGE. All three proteins exhibit the same pentameric, ring-shaped structure in electron microscopy after negative staining. Antibodies raised against the serum galactose binding protein or against the macrophage receptor cross-react. A mAb specific for rat neo-CRP labels liver macrophages but not hepatocytes and reacts with the isolated protein in a Western blot assay. Furthermore, the galactose-particle receptor can be functionally replaced by purified CRP: the binding capacity for neuraminidase-treated E of receptor-depleted liver macrophages can be restored by preincubation with purified rat CRP. We therefore conclude that CRP occurs as a membrane-associated protein constitutively expressed on liver macrophages functioning as a receptor mediating galactose-specific binding of particulate ligands. PMID- 2104908 TI - Anti-idiotype-induced, lipopolysaccharide-specific antibody response to Pseudomonas aeruginosa. AB - Antibody directed to the O-specific polysaccharide (Ps) side chain of Pseudomonas aeruginosa LPS provides immunotype-specific protection against infection by virtue of enhancing opsonophagocytosis. We have developed a syngeneic anti idiotypic antibody (mAb2) directed to a functionally active monoclonal immunotype 1 Ps-antibody (mAb1). The mAb2 performed as a molecular mimic of Ps as evidenced by 1) blocking of mAb1/mAb2 interaction by Ps, 2) blocking of mAb1/Ps binding by mAb2, 3) cross-species binding of mAb2 to human Ps antibodies from individuals immunized with the same immunotype 1 Ps, and 4) induction of anti-LPS antibody by immunization with mAb2 in syngeneic mice. Our studies thus show that an anti idiotypic antibody may functionally mimic the O-polysaccharide of P. aeruginosa LPS, and bind to cross-reactive Id present in human Ps antibodies. We have further shown that this anti-idiotypic antibody induces anti-LPS antibody when used as an Ag in syngeneic mice, suggesting that this approach may eventually be used to successfully immunize humans. PMID- 2104909 TI - Alveolar macrophage function in rats with severe protein calorie malnutrition. Arachidonic acid metabolism, cytokine release, and antimicrobial activity. AB - To investigate the effects of protein calorie malnutrition (PCM) on alveolar macrophage function, we measured antimicrobial activity, IL-1 and TNF production, and arachidonic acid metabolism in alveolar macrophages of infant rats with moderate and severe PCM. Groups of weanling male rats were fed a diet containing 0.8% protein (PCM) or 24% protein (control). A third group (pair fed) was fed limited amounts of the control diet that matched the mean daily dietary intake of the PCM group. After 4 wk on the diets, alveolar macrophages from all three groups functioned similarly with respect to surface adherence, phagocytosis and killing of Listeria monocytogenes, release of hydrogen peroxide and superoxide anion, and production of IL-1 and TNF. In contrast, Listeria-stimulated alveolar macrophages from the PCM group exhibited a marked shift in arachidonic acid metabolism, with impaired production of leukotriene B4 and enhanced release of thromboxane B2 and PGE2. The membrane arachidonic acid content and the uptake of [3H]arachidonate by alveolar macrophages did not differ among the three groups. The shift toward the cyclooxygenase pathway was not seen after 2 wk of dietary restriction and was reversed if PCM animals were fed the control diet for 1 wk. Thus, PCM does not affect the antimicrobial activity or cytokine production of alveolar macrophages, but causes alterations in arachidonic acid metabolism that may interfere with the modulatory functions of alveolar macrophages. PMID- 2104910 TI - Differential expression of the HLA class I multigene family by human embryonal carcinoma and choriocarcinoma cell lines. AB - We have studied the expression of both HLA class and the recently described HLA class I-like genes (HLA-E and HLA-6.0) in two human developmental tumor cell lines, that serologically could not be typed for HLA-A, -B, and -C. Evidence is presented that the teratocarcinoma Tera-2 stem cells express trace amounts of non beta 2 microglobulin-associated classical HLA-A, -B, and -C Ag on their cell surface. The Jeg-3 human choriocarcinoma cells derived from fetal trophoblast express normal levels of surface beta 2 microglobulin associated with 45-kDa and 41-kDa H chains that display unique isoelectric points in IEF gels. The HLA-6.0 or HLA-E genes may encode the lower molecular mass component on Jeg-3 cells, because these genes express molecules of about 38 kDa and 41 kDa, respectively, when transfected to appropriate host cells. Transcripts homologous to the HLA-6.0 gene are found to be constitutively expressed in the Jeg-3 cells but not in Tera 2 cells, whereas HLA-E is not significantly transcribed in either cell line. Transcription of class I (HLA-A, -B, and -C) and class I-like (HLA-E and HLA-6.0) genes is up-regulated after treatment with IFN-gamma in Tera-2 cells, whereas the corresponding genes in Jeg-3 cells remain essentially unresponsive. The biologic role of trophoblast class I(-like) molecules in the context of the maternal acceptance of the fetal semiallograft is discussed. PMID- 2104911 TI - The frequency of multiple recombination events occurring at the human Ig kappa L chain locus. AB - Products of Ig kappa L chain gene rearrangement in a variety of human B cell samples were investigated by sequential Southern blot hybridization analysis. By application of four region-specific probes (C kappa, J kappa, U' kappa and kappa de) a complete spectrum of kappa rearrangements, including both predicted and novel products, were detected. Nearly 30% of the products detected reflect multiple recombination of the kappa locus. The kappa-deleting element was responsible for 70% of the multiple rearrangements that were detected. Interestingly, eight kappa-expressing samples exhibited rearrangement of the kappa-deleting element. The remaining multiple recombination products were characteristic of double V kappa-J kappa rearrangement. This frequency reveals that secondary V-J rearrangement may significantly contribute to the expression of kappa L chains in humans. PMID- 2104912 TI - Molecular cloning of cDNA that encode MHC class I molecules from a New World primate (Saguinus oedipus). Natural selection acts at positions that may affect peptide presentation to T cells. AB - To investigate the evolutionary pressures that drive the generation of polymorphism in primate MHC class I molecules, three cDNA that encode MHC class I alleles from a New World monkey, the cotton-top tamarin (Saguinus oedipus), were cloned and sequenced. These tamarin MHC class I alleles contained amino acid substitutions not found in any of the previously sequenced human MHC class I alleles. Moreover, the majority of these unique amino acid substitutions was located in the Ag recognition site at positions that have been shown to be critical in the presentation of viral peptides to T cells in mice and humans. These data suggest that selective pressures on MHC class I molecules preferentially act on the Ag recognition site and that the peptide binding or presenting functions of these molecules may drive the generation of MHC class I polymorphism. The novel Ag recognition sites of the tamarin MHC class I molecules, in addition to their restricted polymorphism, might account for the unusual susceptibility of the cotton-top tamarin to human pathogens. PMID- 2104913 TI - Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split-dose irradiation. AB - Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells. PMID- 2104914 TI - Hairy cell leukemia-associated antigen (HC2) is an activation antigen of several hemopoietic cell lineages, inducible on monocytes by IFN-gamma. AB - The HC2 Ag is defined by a mAb raised against leukemic B lymphocytes from a patient with hairy cell leukemia (HCL). This 60 to 70-kDa Ag was immunoprecipitated from EBV-transformed B lymphoblastoid cell lines, from HCL-B cells, from the HUT-102 T cell line infected with HTLVI, and from activated monocytes. A binding assay with radioiodinated Fab' anti-HC2 confirmed this cellular distribution of the Ag and demonstrated 500 to 3000 binding sites on resting T cells, 300 to 11,000 binding sites on non-T cells, less than 3000 binding sites on chronic lymphocytic leukemia B cells, and 29,000 to 223,000 binding sites on HCL-B cells. PMA plus anti-CD3 up-regulated HC2 expression on T cells and IFN-gamma up-regulated expression on monocytes. On B cells, EBV transformation may result in HC2 expression, and antibody to HC2 has been found to inhibit B cell differentiation and proliferation. The combined results suggest an important role for the HC2 membrane-associated Ag on cells responsible for the immune response. PMID- 2104916 TI - The antipsoriatic compound anthralin influences bioenergetic parameters and redox properties of energy transducing membranes. AB - Bioenergetic parameters and redox properties of energy transducing membranes in rat liver mitochondria and cyanobacteria were investigated in the presence of the antipsoriatic compound anthralin (1,8-dihydroxy-9-anthrone). Transmembrane pH and electrical gradients were determined using electron paramagnetic resonance spectroscopy. In mitochondria, ubiquinones 9,10 and other redox components of the electron transport chain are reduced by anthralin; the proton motive force is increased. In the absence of ADP, anthralin slightly stimulates mitochondrial cyanide-insensitive oxygen consumption. It is suggested that increased cyanide insensitive respiration is due to enhanced autoxidation of mitochondrial components and/or catalyzed oxidation of anthralin. In the presence of ADP mitochondrial respiration is decreased, and ATP synthesis is inhibited. Uncoupler induced mitochondrial respiration is also decreased by anthralin, indicating inhibition of the electron transport chain. In the cyanobacterium Synechococcus PCC 6311 anthralin increases the pH gradient and decreases ATP levels. Thus, anthralin acts as an electron donor to membrane associated redox components and inhibits ATP synthesis in two different biologic systems. In human keratinocytes oxygen metabolism is influenced by anthralin in a similar pattern as in isolated mitochondria, and ATP content is decreased. Because anthralin reacts with redox components in different biologic membranes, alterations of subcellular/cellular redox status and energy metabolism might contribute significantly to its antiproliferative activity. PMID- 2104915 TI - Resistance of cytolytic lymphocytes to perforin-mediated killing. Inhibition of perforin binding activity by surface membrane proteins. AB - The mechanism whereby cytolytic lymphocytes protect themselves from killing mediated by their own cytotoxic protein, perforin, was studied. By using a competition assay, we demonstrated that the resistance of cells to perforin mediated cytolysis is inversely correlated with their ability to absorb perforin, with tumor cells and noncytotoxic lymphocytes that are susceptible to perforin mediated lysis being able to absorb perforin from the supernatant much better than CTL. The evidence implies that there is molecule on cytolytic lymphocytes that interferes with perforin-binding activity, resulting in the inability of perforin to lyse these cells. The molecule is most likely a surface protein or complex of proteins because its activity decreases after CTL treatment with the proteolytic enzymes trypsin and papain, and the activity can be recovered by incubation of the treated CTL cells at 37 degrees C for 6 h. The recovery can be blocked by emetine, cycloheximide, and actinomycin D, inhibitors of protein and RNA/DNA synthesis. The protein contains carbohydrate groups that play an important role in the function of the protein, as indicated by the fact that inhibition of glycosylation by tunicamycin and cleavage of sialic acid from the protein with neuraminidase result in a significant increase of perforin binding to CTL. Cross-linkage of CTL membrane proteins with glutaraldehyde and formaldehyde and blockage of the functional domains of the protein with an antiserum against CTL also inhibit the activity of this protein. Temperature dependence studies that allow for a dissociation of the binding and pore-forming stages of perforin-mediated hemolysis suggest that the protective protein interferes at the perforin-binding stage. PMID- 2104917 TI - The intracellular fate of Histoplasma capsulatum in human macrophages is unaffected by recombinant human interferon-gamma. AB - Human alveolar, peritoneal, and cultured macrophages were exposed in vitro to human recombinant interferon-gamma (rHuIFN-gamma) and were tested for their ability to inhibit intracellular replication of yeast-phase Histoplasma capsulatum. Exposure at various concentrations, and for different time periods, failed to activate the macrophages to inhibit multiplication of intracellular yeast. Macrophages were, however, activated by rHuIFN-gamma as shown by their ability to inhibit intracellular replication of Trypanosoma cruzi and by their enhanced production of superoxide when stimulated by phorbol myristate acetate. These data indicate that rHuIFN-gamma by itself does not activate human macrophages to inhibit intracellular proliferation of yeast-phase H. capsulatum. PMID- 2104918 TI - Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism. AB - BALB/c mice infected with Leishmania major develop fatal, progressive disease, despite an immune response characterized by expansion of CD4+ T cells in the draining lymph nodes. The immune response has been further characterized by a lack of IFN-gamma mRNA, but increased IL-4 mRNA in lymphoid tissues, and striking elevation of serum IgE. Treatment of infected BALB/c mice with rIFN-gamma at doses shown to be beneficial in other protozoan infections was insufficient to ameliorate L. major infection. In contrast, neutralization of IL-4 by six weekly injections of mAb 11B11 led to attenuation of disease in 100% of animals, and complete cure in 85%. Resolution of disease required the presence of T cells, and recovered mice remained resistant to reinfection at 12 wk. This immunity was adoptively transferable and was dependent on both CD4+ and CD8+ cells. Although administration of anti-IL-4 was associated with fourfold increase in IFN-gamma mRNA in lymph node cells draining the lesion, the coadministration of neutralizing R4 6A2 anti-IFN-gamma mAb had no effect on resistance to disease. This was in marked contrast to resolution of disease in both resistant C57BL/6- and GK1.5-pretreated BALB/c mice that was abrogated by in vivo treatment with anti-IFN-gamma. These data suggest a novel mechanism of cellular immunity established by interference with the development of Th2 cells during infection. PMID- 2104920 TI - A mycobacterial 65-kD heat shock protein induces antigen-specific suppression of adjuvant arthritis, but is not itself arthritogenic. AB - A recombinant (r)65-kD protein from Mycobacterium leprae, at levels far in excess of those present in whole mycobacteria, was unable to induce arthritis. Even when combined with a synthetic adjuvant, CP20961, to mimic the peptidoglycan adjuvant component of the mycobacterial cell wall, the r65-kD protein failed to induce arthritis. Pretreatment with as little as 1 microgram r65-kD protein protected rats against arthritis induced by M. tuberculosis, but this r65-kD protein was markedly less able to protect against arthritis induced by the synthetic adjuvant, CP20961, or type II collagen. The r65-kD protein appears, therefore, to produce an antigen-specific protection against arthritis induced by bacterial cell walls containing the 65-kD protein. Such protection can be overcome, however, by arthritogenic T lymphocytes, suggesting that protection occurs by preventing clonal proliferation of autoreactive T lymphocytes that are induced by the adjuvant properties of mycobacterial cell walls. How the r65-kD protein abrogates this particular adjuvant activity, and the nature of the arthritogenic self antigen(s), remain to be elucidated. PMID- 2104919 TI - Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. AB - The proximate cause of autoantibodies characteristic of systemic autoimmune diseases has been controversial. One hypothesis is that autoantibodies are the result of polyclonal nonspecific B cell activation. Alternatively, autoantibodies could be the result of antigen-driven B cell activation, as observed in secondary immune responses. We have approached this question by studying monoclonal anti DNA autoantibodies derived from unmanipulated spleen cells of the autoimmune MRL/lpr mouse strain. This analysis shows that anti-DNAs, like rheumatoid factors (19), are the result of specific antigen-driven stimulation. In addition, correlation of sequences with fine specificity shows that: (a) somatic mutations can cause specificity for dsDNA and that such mutations are selected for; (b) arginine residues play an important role in determining specificity; and (c) anti idiotypes that recognize the majority of anti-DNA are probably not specific for any one family of V regions. PMID- 2104921 TI - Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. AB - We have explored the cis-acting elements necessary for the LPS-mediated activation of the mouse TNF-alpha promoter by transfecting a set of 5' deletion mutants linked to the CAT reporter gene into primary bone marrow-derived macrophages. A major drop in inducibility by LPS was seen upon deletion of a region mapping between nt -655 and nt -451. Gel retardation assays revealed that LPS induced the appearance in this region of several specific DNA-protein complexes mapping to sequence motifs with strong homology to the kappa B enhancer. Constructs containing two or more copies of one of the kappa B enhancer motifs linked to a heterologous promoter were inducible by LPS. Additional deletion of a region between nt -301 and nt -241, which contains a MHC class II like "Y box" and formed a Y box-specific complex with a protein whose concentration was increased by LPS, caused a nearly complete loss of inducibility by LPS. We speculate that NF-kappa B and/or related proteins are involved in the LPS-induced transcriptional activation of the TNF-alpha gene, and that factors interacting with the Y box can additionally modulate the activity of the gene in macrophages. PMID- 2104922 TI - Polymorphic DQ alpha and DQ beta interactions dictate HLA class II determinants of allo-recognition. AB - 18 transfected cell lines were generated that expressed distinct DQ molecules related to the serologically defined HLA-DQw3 specificity. These transfectants were constructed using site-directed mutagenesis to introduce nucleotide substitutions into DQ3.2 beta cDNA, followed by retrovirus-mediated gene expression of the mutagenized genes in human B cell lines with different endogenous DQ alpha chains. The capacity of particular class II dimers to stimulate alloreactive T cell clones was investigated. T cell activation was found to be dependent on both DQ alpha and DQ beta chains. In some cases, single amino acid substitutions at codons 13, 26, 45, or 57 of the DQ beta chain were sufficient to dramatically alter T cell reactivity; T cell recognition of these substitutions, however, was strongly influenced by the alpha chain polymorphisms present in the stimulatory class II dimer. Both gain and loss of major serologic and cellular specificities associated with specific DQw3+ alleles were observed with a limited array of site-directed substitutions. PMID- 2104923 TI - High-dose ifosfamide with mesna uroprotection: a phase I study. AB - Phase II trials of ifosfamide have been performed with standard doses of 5 to 8 g/m2/course. In this phase I study, 29 patients were treated with a 4-day continuous infusion ifosfamide to determine the maximum-tolerated dose and the nonhematologic dose-limiting toxicity. Autologous bone marrow support was to have been used for the subsequent dose level if granulocytes were more than 500/microL for more than 14 days in two of two to five patients at a given dose level. Doses were escalated from 8 to 18 g/m2 ifosfamide. Mesna was given at an equivalent dose by continuous infusion for 5 days. At the 18 g/m2 dose level, dose-limiting renal insufficiency and a median of 11 days (range, 8 to 18 days) of granulocytopenia (less than 500/microL) were observed. Thus, autologous bone marrow reinfusion ws not used. The duration of myelosuppression, the frequency and severity of mucositis, and renal tubular acidosis were all dose-dependent. Mild to moderate CNS toxicity also appeared to be related to dose; however, severe CNS toxicity (transient confusion, hallucinations, and somnolence) was observed sporadically at both low- and high-dose levels. Transient hematuria (greater than 50 red blood cells [RBCs]/high power field) occurred once but did not affect treatment. There were nine responses (two complete) in 27 heavily pretreated assessable patients including seven responses in 20 patients with advanced refractory sarcoma. Ifosfamide with mesna uroprotection can undergo considerable dose escalation over the usual prescribed doses before nonhematologic dose-limiting toxicity is encountered. Ifosfamide has broad cytotoxicity against solid tumors and may prove to be an important addition to high-dose combination chemotherapy regimens. PMID- 2104924 TI - Capillary permeability factor secreted by malignant brain tumor. Role in peritumoral brain edema and possible mechanism for anti-edema effect of glucocorticoids. AB - Conditioned media from two human malignant gliomas, C6 rat glioma, Walker 256 carcinosarcoma, and normal human glia were concentrated 50-fold to create a culture supernatant (SUP-C). The effect of SUP-C on rat brain capillary permeability was investigated by measuring the entry of 14C-aminoisobutyric acid (14C-AIB) by means of quantitative autoradiography. The SUP-C contained proteins with a molecular weight of 10 kD or greater. The SUP-C from all tumor cells markedly increased brain capillary permeability, indicating the presence of a permeability factor, whereas that from normal glial cells did not. Glioma cells produced more factor after incubation for 20 hours than 4 hours. The activity of capillary permeability factor in the SUP-C was inhibited by pretreatment of animals with BW755C (lipoxygenase inhibitor), but not with indomethacin (cyclo oxygenase inhibitor). Pretreatment of animals with dexamethasone prior to intracerebral infusion of tumor SUP-C significantly reduced the factor-induced increase in capillary permeability. On the other hand, coincubating glioma cells with dexamethasone produced SUP-C with a permeability activity that was about one and a half times greater than that without dexamethasone. These results indicate that glucocorticoids produce their anti-edema effects by directly acting on capillary endothelial cells, possibly through the inhibition of phospholipase A2 activity, resulting in a decrease of lipoxygenase rather than cyclo-oxygenase products. The production of capillary permeability factor by tumor cells was not inhibited, but rather enhanced, by administration of glucocorticoids. PMID- 2104925 TI - Indium-111 WBC detection of emphysematous gastritis in pancreatitis. AB - We present a case of emphysematous gastritis initially detected with 111In oxine labeled white blood cell scintigraphy and subsequently confirmed by computed tomography. Early aggressive antibiotic and supportive therapy resulted in a successful clinical outcome. PMID- 2104926 TI - How should cost-containment be attained? Congress forges a plan. PMID- 2104927 TI - Topical use of nitroglycerin ointment in neonates. PMID- 2104928 TI - Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functioning in young children. AB - Because prenatal exposure to polychlorinated biphenyls (PCBs) and related contaminants has been associated with reduced birth weight, neonatal behavioral anomalies, and poorer recognition memory in infants born to women who have consumed Lake Michigan sports fish, 236 children, previously evaluated for PCB related deficits in infancy, were assessed at 4 years of age. Prenatal exposure (indicated by umbilical cord serum PCB level) predicted poorer short-term memory function on both verbal and quantitative tests in a dose-dependent fashion. These effects cannot be attributed to a broad range of potential confounding variables, the impact of which was evaluated statistically. Although much larger quantities of PCBs are transferred postnatally via lactation than prenatally across the placenta, exposure from nursing was unrelated to cognitive performance. The data demonstrate the continuation of a toxic impact received in utero and observed initially during infancy on a dimension of cognitive functioning fundamental to learning. PMID- 2104929 TI - Using unstimulated urinary lead excretion to assess the need for chelation in the treatment of lead poisoning. AB - To determine whether unstimulated urine samples could be used to identify children needing chelation therapy for lead poisoning, we compared urinary lead excretion with and without chelation. A convenience sample of 39 children was admitted to a pediatric clinical research center for therapeutic chelation. Urine was collected for 24 hours on 2 consecutive days. Edetate disodium calcium, 1000 mg/m2, was given intramuscularly in two divided doses on the second day. Significant correlations existed between urinary lead excretion (PbU) on the control day at 12- and 24-hour collection intervals and on the first day of chelation (p less than 0.0001). Published criteria for positive edetate disodium calcium provocative tests were used to calculate corresponding cutoff points for unstimulated 24-hour PbU. Resultant PbU values ranged from 10.4 to 35.6 micrograms (0.05 to 0.17 mumol). When PbU was expressed in terms of creatinine excretion, cutoff points of 0.06 and 0.19 microgram PbU/mg creatinine were determined, making possible the use of random unstimulated samples to assist in the identification of children in need of chelation. PMID- 2104930 TI - Complex I (reduced nicotinamide-adenine dinucleotide-coenzyme Q reductase) deficiency in two patients with probable Leigh syndrome. AB - Two infants who had clinical and radiographic findings consistent with Leigh syndrome were found to have deficiency of complex I (reduced nicotinamide-adenine dinucleotide--coenzyme Q reductase) activity. Significant abnormalities were found on computed tomographic scans and magnetic resonance images of the brain. Lactate and pyruvate concentrations in blood and cerebrospinal fluid were elevated, and muscle biopsy specimens showed abnormal mitochondria. These data indicate that Leigh syndrome, as well as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes) may result from complex I deficiency. PMID- 2104931 TI - Listeriosis in patients with HIV infection: clinical manifestations and response to therapy. AB - Although listeriosis is an uncommon infection in patients with human immunodeficiency virus (HIV) infection, the frequency of listeriosis in New York City has increased because of the increase in the number of HIV-infected patients. The medical records of 30 patients admitted to three medical centers in New York City from 1981 to 1988 with infections due to Listeria monocytogenes were reviewed. Six patients had AIDS, one was seropositive and asymptomatic, and four had risk factors for HIV infection. While the annual number of cases of listeriosis in patients without risk factors for HIV infection was constant, 9 of the 11 patients with AIDS or with risk factors for HIV infection presented with listeriosis between 1985 and 1988, the last half of the survey period. These patients were male homosexuals or intravenous drug abusers, and all but one were black or Hispanic. Manifestations of listeriosis in patients with AIDS or with risk factors for HIV infection included bacteremia without apparent source in seven, meningitis in three, and endocarditis in one, syndromes that were similar to those in patients without risk factors for HIV infection. Ten of 11 patients were treated with penicillin or ampicillin, and 7 were also given an aminoglycoside. All patients responded well to therapy and no relapses were observed. Physicians should include antibiotics effective against L. monocytogenes when treating AIDS patients with meningitis of unknown origin and consider the diagnosis of listeriosis in patients with sepsis of unknown origin. PMID- 2104932 TI - Measuring the impact of P.L. 99-252: an economist's view. AB - This paper examines ways in which standard economic analysis may be used to predict and evaluate the impact of P.L. 99-252, the Comprehensive Smokeless Tobacco Health Education Act of 1986. Simple supply and demand models are used to illustrate the range of possible effects of the act. Analysis indicates that the act should reduce demand, though the magnitude of the impact can only be determined empirically. Given that the act affects only one of the principal determinants of demand, consumer preferences, the impact may be rather limited in magnitude. The impact on supply is more ambiguous, but it is possible that restrictions on advertising might lower the smokeless tobacco producers' costs in ways that would lead to an increase in supply. Several suggestions for empirical measurement of impact are made. Three other issues are identified and discussed: potential negative consequences of the act's required health warnings (as a liability defense for firms); the importance of point of view in dealing with the costs of smokeless tobacco use; and a comparison of the act to alternative strategies to reduce smokeless tobacco use, such as taxation. PMID- 2104933 TI - Anticandidal properties of N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid oligopeptides. AB - Tri-, tetra-, and pentapeptides containing N3-(4-methoxyfumaroyl)-L-2,3 diaminopropanoic acid (FMDP), an inactivator of glucosamine 6-phosphate synthase of fungal origin (a key enzyme in the biosynthesis of macromolecular components of the fungal cell wall) have been synthesized and investigated as anticandidal agents. Structure-activity relationships of a series of peptides revealed that tripeptides were generally more active than the other peptides examined. In this study, the lysyl peptide, Lys-Nva-FMDP has been found to be the most active compound in the series. PMID- 2104934 TI - Synthesis and structure-activity relationships of new 7-[3 (fluoromethyl)piperazinyl]- and -(fluorohomopiperazinyl)quinolone antibacterials. AB - Some novel 6-fluoro-7-substituted-1,4-dihydro-4-oxoquinoline-3-carboxylic acids have been prepared. At the N-1 position "standard" substitution was employed with the ethyl, cyclopropyl, and p-fluorophenyl groups being used. At C-7 the introduction of some novel piperazines was made. Most notably, 2 (fluoromethyl)piperazine (10) and hexahydro-6-fluoro-1H-1,4-diazepine (16, fluorohomopiperazine) at the quinolone C-7 position produced products with similar in vitro antibacterial activity as the ciprofloxacin reference. The in vivo efficacy of 1-cyclopropyl-6-fluoro-7-[3-(fluoromethyl)piperazinyl]-1,4 dihydro-4- oxoquinoline-3-carboxylic acid (20) was excellent with better oral absorption than ciprofloxacin (2). PMID- 2104935 TI - N-[(arylmethoxy)phenyl] carboxylic acids, hydroxamic acids, tetrazoles, and sulfonyl carboxamides. Potent orally active leukotriene D4 antagonists of novel structure. AB - Four series of N-[(arylmethoxy)phenyl] compounds were prepared as leukotriene D4 (LTD4) antagonists. In the hydroxamic acid series, methyl 3-(2 quinolinylmethoxy)benzeneacetohydroxamate (Wy-48,422, 20) was the most potent inhibitor of LTD4-induced bronchoconstriction with an oral ED50 of 7.9 mg/kg. Compound 20 also orally inhibited ovalbumin-induced bronchoconstriction in the guinea pig with an ED50 of 3.6 mg/kg. In vitro, against LTD4-induced contraction of isolated guinea pig trachea pretreated with indomethacin and 1-cysteine, 20 produced a pKB value of 6.08. In the sulfonyl carboxamide series, N-[(4 methylphenyl)sulfonyl]-3-(2-quinolinylmethoxy)-benzamide (Wy-49,353, 30) was the most potent antagonist. Compound 30 orally inhibited both LTD4- and ovalbumin induced bronchoconstriction with ED50s of 0.4 and 20.2 mg/kg, respectively. In vitro, against LTD4-induced contraction of isolated guinea pig trachea, 30 produced a pKB value of 7.78. In the carboxylic acid series, which served as intermediates for the above two series, 3-(2-quinolinylmethoxy)benzeneacetic acid (Wy-46,016, 5) was the most potent inhibitor of LTD4-induced bronchoconstriction (99% at 25 mg/kg, intraduodenally); however, the pKB for this compound was disappointing (5.79). In the tetrazole series, the most potent inhibitor was 2 [[3-(1H-tetrazol-5-ylmethyl)phenoxy]methyl]quinoline (Wy-49,451, 41). The respective inhibitory ED50s were 3.0 mg/kg versus LTD4 and 17.5 mg/kg versus ovalbumin. In the isolated guinea pig trachea, 41 produced a pKB value of 6.70. PMID- 2104936 TI - 2-substituted-1-naphthols as potent 5-lipoxygenase inhibitors with topical antiinflammatory activity. AB - The synthesis, biological evaluation, and structure-activity relationships of a series of 1-naphthols bearing carbon substituents at the 2-position are described. These compounds are potent inhibitors of the 5-lipoxygenase from RBL-1 cells and also inhibit bovine seminal vesicle cyclooxygenase. Structure-activity relationships for these two enzymes are different, implying specific enzyme inhibition rather than a nonspecific antioxidant effect. 2-(Aryl-methyl)-1 naphthols are among the most potent 5-lipoxygenase inhibitors reported (IC50 values generally 0.01-0.2 microM) and show excellent antiinflammatory potency in the mouse arachidonic acid ear edema model. To study the effects of structure on in vitro and in vivo activity, four general features of the molecules were varied: the 2-substituent, the 1-hydroxyl group, substitution on the naphthalene rings, and the 1,2-disubstituted naphthalene unit itself. 2-Benzyl-1-naphthol (5a, DuP 654) shows a very attractive profile of topical antiinflammatory activity and is currently in clinical trials as a topically applied antipsoriatic agent. PMID- 2104937 TI - Phase II study of recombinant human interferon gamma for treatment of cutaneous T cell lymphoma. AB - Recombinant human interferon gamma (rIFN-gamma) was used for the treatment of 16 patients with various stages of cutaneous T-cell lymphoma (CTCL). All patients had been previously treated with standard topical and/or systemic therapies, and some had received experimental treatment with retinoids, recombinant human interferon alfa-2a (rIFN-alpha 2a), or radiolabeled monoclonal antibodies; most patients had an advanced stage of disease. Objective partial responses (PRs) were noted in five patients (31%) and lasted 3 months to greater than 32 months (median, 10 mo). One of these five patients had previously had disease progression after an initial PR with rIFN-alpha 2a. Six other patients (38%) showed minor or mixed responses. The most common side effects of rIFN-gamma included fever, weight loss, mild neutropenia, elevated lactate dehydrogenase, and elevated hepatic transaminases. Additionally, one episode of nephrotic syndrome and one cutaneous allergic reaction were noted. None of the toxic effects were life threatening, and all were reversible. These results suggest that rIFN-gamma has efficacy in the treatment of CTCL refractory to rIFN-alpha 2a. PMID- 2104938 TI - Efficient tumor suppression by glioma-specific murine cytotoxic T lymphocytes transfected with interferon-gamma gene. AB - We have recently shown that exogenous expression of the mouse interferon-gamma (IFN-gamma) gene augmented the cell-killing potential of a line of cytotoxic T lymphocytes (CTLs) specific against a murine glioma line (203-glioma). In the present work, we further investigated the in vivo antitumor effects of the E gamma-6 and E gamma-9 sublines of this CTL line transfected with the IFN-gamma gene. Using the Winn assay to test the neutralization of subcutaneous gliomas, we determined that these CTL sublines were more effective than the E-4 parent CTL line and that suppression of the tumor growth was dependent on the number of effector cells (CTLs). Moreover, intravenous injection of E gamma-9 cells was more effective in suppressing the tumor growth than intravenous injection of E-4 cells. These results suggest that transfection of antitumor effector cells with the IFN-gamma gene could improve the efficacy of adoptive immunotherapy against cancer. PMID- 2104939 TI - Immunoprotective effects of cyclooxygenase inhibition in patients with major surgical trauma. AB - Dysfunctional monocytes (M phi), exerting their inhibitory functions via prostaglandin E2 (PGE2), have been implicated in the depression of immune responses following major surgical, accidental, and burn trauma. A randomized prospective study of the PG-synthetase inhibitor indomethacin (Indo) was performed in 43 patients undergoing major surgical procedures, to evaluate its efficacy in correcting postoperative abnormalities of the cell-mediated immune system (CMI) and preventing infectious morbidity and mortality. Patients, following gastrectomy (GX) or reconstruction of the abdominal aorta (AG), in the treated group (PIndo), received 100 mg IV of Indo 6 hours postoperatively and 3 x 50 mg IV Indo over 24 hours on postoperative days (D) 1,2,3,4. The rate of infectious complications was recorded. Parameters of CMI evaluated preoperatively (D0) and on D1,D3,D5,D7 were: Delayed type hypersensitivity (DTH) response to recall antigens, mitogen-induced lymphocyte proliferation (LP), interleukin 2 (IL 2) synthesis, and phenotyping of mononuclear blood leukocytes (PBMC's) with the monoclonal antibodies for CD3+, CD4+, IL-2 receptor (IL-2R)+ and LeuM3+ receptor sites. In contrast to the group of untreated patients (Pc), PIndo did not show a depression of their preoperative DTH responses, and they also showed a lower rate of early opportunistic infections. The in vitro test of CMI revealed that there was a higher LP capacity in PBMC's of PIndo (p less than 0.05); the postoperative profile of IL-2 synthesis was not statistically different between the groups. Indomethacin administration resulted in a considerable alleviation of postoperative monocytosis (p less than 0.05) and in a protective effect on lymphocyte receptor expression of CD3+, CD4+, and IL-2R+ cells. From these data it is concluded that in vivo cyclooxygenase inhibition may be useful to prevent impairment of CMI, a crucial predisposing factor of the high susceptibility to postoperative infection. PMID- 2104940 TI - Obstetric duplex sonography in patients with lupus anticoagulant syndrome. AB - The lupus anticoagulant (LAC) syndrome has recently been described as a potential cause of many cases of preeclampsia. This syndrome is associated with a maternal history of repeated first trimester abortions and second and third trimester demise in utero. Umbilical arterial duplex Doppler systolic/diastolic (S/D) ratios and uterine artery S/D ratios for 28 patients whose pregnancies were complicated by lupus anticoagulant syndrome are presented. Five of the six patients who subsequently delivered fetuses small for gestational age (SGA) demonstrated abnormal umbilical arterial S/D ratios, whereas only two of these patients demonstrated abnormally elevated uterine S/D ratios. Twenty three of 28 patients were treated with aspirin and prednisone throughout gestation; no cases of fetal demise in utero were noted. PMID- 2104941 TI - Characterization and purification of human fos protein generated in insect cells with a baculoviral expression vector. AB - We generated recombinant baculoviruses that contained the human fos gene and that, upon infection of insect cells, synthesized fos protein. The quantity of fos protein produced was at least 10 to 20 times higher than that observed in any mammalian cells reported so far. The fos protein made in insect cells manifested most of the characteristics of mammalian fos protein, which include (i) 55 kilodalton size, (ii) nuclear localization, (iii) phosphoesterification at serine residues, (iv) identical 35S tryptic peptide maps, (v) ability to make heterodimers with the nuclear jun oncoprotein, and (vi) cooperation with the jun protein to bind to a 12-O-tetradecanoyl-phorbol-13-acetate-responsive element. A 100- to 150-fold purification of the fos protein from infected insect cells was achieved in a single step by immunoaffinity chromatography. Availability of authentic fos protein made by baculoviral vectors in insect cells should allow a more rigorous analysis of its biochemical and biological properties. PMID- 2104943 TI - End-tidal PCO2 during cardiopulmonary resuscitation. PMID- 2104944 TI - Does t-PA have a role in the treatment of crescentic glomerulonephritis? PMID- 2104942 TI - Point mutations in the Moloney murine leukemia virus enhancer identify a lymphoid specific viral core motif and 1,3-phorbol myristate acetate-inducible element. AB - The transcriptional enhancer of the Moloney murine leukemia virus (MoMLV) is organized as a 75-base-pair repeat, and in each copy of the repeat there are multiple binding sites for nuclear factors. We have introduced point mutations into each of the known nuclear factor-binding sites in the MoMLV enhancer, in both copies of the direct repeat, and have analyzed the transcriptional activity conferred by the mutated enhancers by transient-expression assays in both hematopoietic and nonhematopoietic cell lines. Mutation of individual binding sites in the MoMLV enhancer has moderate effects (less than 2-fold to 20-fold) on transcription in six independent cell lines. Several mutations decreased transcription from the MoMLV enhancer ubiquitously (the leukemia virus factor b site and the glucocorticoid response element), whereas others affected transcription specifically in lymphoid cell lines (core motif) or, more significantly, in fibroblasts (nuclear factor 1 site). The transcriptional activity of the MoMLV enhancer can be induced 8- to 10-fold by 1,3-phorbol myristate acetate in Jurkat T cells. Mutations in any of three adjacent binding sites (leukemia virus factor b and c sites and the core motif) within a 28-base pair region in the center of the direct repeat sequence of the MoMLV enhancer completely attenuate the response to 1,3-phorbol myristate acetate. PMID- 2104945 TI - Effect of propranolol on nitrogen and energy metabolism in sepsis. AB - Pharmacologic therapy designed to block adrenergic activity or alter hormonal milieu may modulate energy and protein metabolism in stress. The metabolic effects of propranolol (beta adrenergic receptor blocker) in sepsis was investigated in 22 well-nourished rats that underwent superior vena caval cannulation, cecal ligation, and puncture. Animals were randomly assigned to receive either a continuous infusion of 0.7 mg/day of propranolol combined with parenteral nutrition (n = 11) or parenteral nutrition alone (n = 11). Both groups received isocaloric, isonitrogenous, isovolemic, parenteral nutrition post operatively for 24 hr. Nitrogen balance was better for the propranolol group than for the control group (+743 +/- 84 mg/kg/day versus +300 +/- 63 mg/kg/day, respectively, P less than 0.05). A significant difference between the pharmacologic therapy and control groups was noted for urinary 3-methylhistidine excretion versus control (0.99 +/- 0.08 micrograms/kg/day versus 7.5 +/- 0.37 micrograms/kg/day, respectively, P less than 0.01). Measured energy expenditure was similar for both pharmacologic therapy and control groups (149 +/- 20 kcal/kg/day versus 134 +/- 11 kcal/kg/day, respectively, P = N.S.). No statistically significant difference was demonstrated for 24-hr survival between propranolol and control groups (73 and 64%, respectively). Continuous, low-dose propranolol promotes nitrogen retention and decreases 3-methylhistidine excretion without altering energy expenditure in parenterally fed septic rats. PMID- 2104946 TI - Cobalt as a gastric juice volume marker: comparison of two methods of estimation. AB - We investigated the use of cobalt-EDTA, a novel, nonabsorbable liquid phase marker, in the estimation of secretory volumes during topical misoprostol (synthetic PGE, analog) administration in the canine chambered gastric segment. We compared atomic absorption spectrophotometry (AAS) and instrumental neutron activation analysis (INAA) in the estimation of [Co]. Mucosal bathing solutions containing cobalt-EDTA were instilled into and recovered from the chamber by gravity every 15-min period as follows: (i) basal--60 min; (ii) misoprostol periods--150 min (plus 0.1-, 1-, 10-, 100-, and 1000-micrograms doses of misoprostol for two periods per dose). The recovered solutions were analyzed for [Co] by AAS and INAA. Total cobalt recovery by AAS after chamber washout was 102.97 +/- 0.98%. Mean +/- SE volumes (12.14 +/- 0.33 and 13.24 +/- 0.60 ml/15 min) obtained respectively from AAS and INAA were significantly higher (P less than 0.001) than the recovered mean volumes (10.51 +/- 0.17 ml/15 min). The percentage error in volume collection increased (range: 9.3-52.7%) with the volume of secretion. Values of [Co] obtained by the two techniques were comparable and not significantly different from each other (P greater than 0.05). INAA-estimated mean +/- SE [Co] showed consistently higher coefficients of variation. Spectra obtained for all samples during INAA measurements showed significant Compton background activity from 24Na and 38Cl. Cobalt-EDTA did not grossly or histologically damage the gastric mucosa. We conclude that cobalt is not adsorbed, absorbed, or metabolized, and is a suitable and reliable volume marker in this model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2104947 TI - Management of children and adolescents with inflammatory bowel disease. AB - The management of children and adolescents with inflammatory bowel disease requires all the skills offered by the health care team. This article reviews the principles of therapy, the specifics of therapy, and the attitudes of the authors relating to long-term management of these patients. Specific recommendations relating to nutritional support for patients are also made. A pertinent updated bibliography is also given. PMID- 2104948 TI - Complications associated with the insertion of narrow-bore feeding-tubes. PMID- 2104949 TI - How well are endoscopes cleaned and disinfected between patients? PMID- 2104950 TI - What every doctor should know about economics. Part 2. The benefits of economic appraisal. AB - In this article we have discussed a number of aspects of economic appraisal. Economic evaluation considers both costs and benefits. Cost-benefit analysis requires the evaluation of health in dollar terms but allows the comparison of health programmes with other programmes or the evaluation of one project alone. Because of the problems that are associated with placing a monetary value on life and health, cost-benefit analysis has not been used in the health field as extensively as has cost-effectiveness analysis. Cost-effectiveness analysis is used to compare alternative programmes with the same health goal. The importance of quality as well as length of life as health outcomes has led to the development of cost-utility analysis. Finally, a good economic evaluation of health care requires the collaboration of clinicians and health economists. PMID- 2104951 TI - Amyloidosis of immunoglobulin origin: useful treatment? AB - Six patients are presented in whom a diagnosis of amyloidosis of immunoglobulin origin was established by light and electron microscopy of biopsy samples. Treatment with a regimen of intermittent doses of melphalan and prednisone resulted in a survival of 48-82 months in four of the patients while two patients died within three months of diagnosis, too soon for the therapy to have been effective. When compared with published series which suggest that the median survival of this condition is approximately 14 months, our results suggest that this treatment prolongs life successfully. These patients also enjoyed a greatly improved quality of life while receiving treatment. PMID- 2104952 TI - Thiamin fortification and alcohol. PMID- 2104953 TI - Tetanus--United States, 1987 and 1988. PMID- 2104954 TI - Surveillance of shelters after Hurricane Hugo--Puerto Rico. PMID- 2104955 TI - Pseudomonas aeruginosa corneal infection related to mascara applicator trauma- Georgia. PMID- 2104956 TI - Aspergillus endophthalmitis in intravenous-drug users--Kentucky. PMID- 2104957 TI - Update: influenza activity--United States, 1989-90. PMID- 2104958 TI - Erythropoietin for the treatment of porphyria cutanea tarda in a patient on long term hemodialysis. PMID- 2104959 TI - Go protein as signal transducer in the pertussis toxin-sensitive phosphatidylinositol pathway. AB - Receptors stimulating phospholipase C do so through heterotrimeric GTP-binding proteins to produce two second messengers, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol. In spite of the detailed understanding of phospholipase C structure and phosphatidyl inositol signalling, the identity of the GTP-binding protein involved is so far unknown. To address this issue, we have used the Xenopus oocyte in which muscarinic receptors couple to phospholipase C through a pertussis toxin-sensitive GTP-binding protein. In this cell, InsP3 mobilizes intracellular Ca2+ to evoke a Cl- current. The magnitude of this Cl- current is proportional to the amount of InsP3 in the cell, and therefore can be used as an assay for InsP3 production. We report here that the activated alpha-subunit of the GTP-binding protein GO, when directly injected into oocytes, evokes a Cl- current by mobilizing Ca2+ from intracellular InsP3-sensitive stores. We also show that holo-GO, when injected into oocytes, can specifically enhance the muscarinic receptor-stimulated Cl- current. These data indicate that GO can serve as the signal transducer of the receptor-regulated phospholipase C in Xenopus oocytes. PMID- 2104960 TI - Structure and evolution of a human erythroid transcription factor. AB - Vertebrate erythroid cells contain a tissue-specific transcription factor referred to as Eryf 1 (ref. 1), GF-1 (ref. 2) or NF-E1 (ref. 3), for which binding sites are widely distributed in the promoters and enhancers of the globin gene family, and of other erythroid-specific genes. Aberrant binding of the human factor to a mutant site has been implicated in one form of hereditary persistence of fetal haemoglobin (HPFH; ref. 2). The complementary DNAs for both the chicken cEryf 1 (ref. 11) and mouse mEryf 1 (ref. 12) encoding genes have recently been cloned. We report here the cloning of the cDNA for the human Eryf 1 encoding gene. The central third of the hEryf 1 cDNA, containing two 'finger' motifs, is almost identical to that of chicken or mouse. The amino-and carboxy-terminal thirds of the human protein are similar to those of mouse, but are strikingly different from the corresponding domains in chicken. The evidence indicates that these erythroid regulatory factors evolved from a common precursor composed of two distinct kinds of repeated domains, which subsequently evolved at greatly different rates. PMID- 2104961 TI - [End of the century]. PMID- 2104962 TI - [Tube feeding and decision policy]. PMID- 2104963 TI - Mechanism of normochloremic and hyperchloremic acidosis in diabetic ketoacidosis. PMID- 2104964 TI - Failure of prostacyclin to improve peripheral arterial disease in dialysis patients. PMID- 2104965 TI - Common dopaminergic mechanism for epileptic photosensitivity in progressive myoclonus epilepsies. AB - We studied the effect of apomorphine, a dopamine receptor agonist, on epileptic photosensitivity in 7 patients with progressive myoclonus epilepsy (PME). Specific diagnoses included Baltic PME (Unverricht-Lundborg disease), Lafora disease, Kufs' disease, juvenile neuroaxonal dystrophy, and action myoclonus renal failure syndrome; 2 patients had PME of uncertain etiology. Apomorphine blocked the epileptic photosensitivity in all patients and also reduced intention myoclonus in a patient with Baltic PME. There is a common deficit of dopaminergic inhibitory neurotransmission at the level of the striate cortex in patients with PME, regardless of the nature of the specific underlying neuropathologic process. PMID- 2104966 TI - Focal functional anatomy of dorsolateral frontocentral seizures. AB - We compared 6 patients with dorsolateral frontocentral seizures to 7 patients with temporal lobe seizures. We determined general seizure location by structural lesions in 7 patients, bilateral depth electrodes in 4, and EEG and semiology in 2. We then mapped seizure cortex and essential cortex using chronic ECoG arrays. Two ECoG patterns were similar in frontal and temporal seizures. Focal patterns were near lesions and resections. Regional patterns were distant from lesions but not associated with worse surgical outcome. "Dipolar" seizure patterns occurred in one-half of frontal patients with maps like somatosensory evoked responses, consistent with focal seizure anatomy and involvement of sensorimotor cortex. Dipole location estimates were near centers of seizure cortex determined by lesions, semiology, and outcome. Six temporal patients had focal excisions that gave significant seizure reduction in all. All frontocentral patients had focal excisions that significantly reduced seizures except in 1 patient with progressive disease. We conclude that dorsolateral frontocentral seizures have focal functional anatomy that can be predicted by ictal ECoG. PMID- 2104967 TI - Accumulation of penicillin in vaginal fluid. AB - The excretion of phenoxymethylpenicillin in vaginal fluid was determined in five women after intake of a single dose of 1 g phenoxymethylpenicillin and in five women on a 10-day medication scheme with 1 g twice daily. After the single dose, there was a steady increase of penicillin in vaginal secretion during the following 3 hours. During the same period, the concentrations in serum and saliva peaked and started to decline. Fifteen hours after intake, vaginal fluid contained more than 1 mg/L, whereas no activity was found in serum or saliva. During the 10-day course of treatment, vaginal concentrations ranged between 2-3 mg/L. The drug was not eliminated from the vagina until the second day after ceasing medication. The accumulation and slow pharmacokinetics of phenoxymethylpenicillin in the vagina may be explained by the countercurrent vascular system supplying the internal genitalia and upper vagina. The effect of the high concentrations of penicillin on the vaginal microflora is discussed. PMID- 2104968 TI - Osteophytic reaction to a polytetrafluoroethylene temporomandibular joint implant. Report of a case. AB - Alloplastic disk substitutes of polytetrafluoroethylene (PTFE) used in the management of late stage temporomandibular joint disease have often been accompanied by morbid tissue reactions and resultant destructive changes. Numerous clinicians have reported cases of severe radiographic and clinical bony destruction and degeneration accompanied by marked foreign body giant cell reactions in the adjacent soft tissues. The case reported here demonstrates just the opposite event. Osteophytic enlargement of the lateral portion of the zygomatic arch and glenoid fossa, with adaptation to the contours of the implant, along with severe condylar osteophytosis, was diagnosed through tomographic and CT imaging and was confirmed at surgery. PMID- 2104969 TI - [Detection of antimitochondrial antibodies by immunodiffusion, ELISA and immunofluorescence methods]. AB - Ouchterlony immunodiffusion and ELISA were used for the detection of antimitochondrial antibodies. The results were compared with those of immunofluorescence measurements. The occurrence of antimitochondrial antibodies was investigated in 20 patients with primary biliary cirrhosis, in 30 with autoimmune disease and in 28 with porphyria cutanea tarda. Sonicated rat liver mitochondria fractions were used as antigens. Among the patients with primary biliary cirrhosis, Ouchterlony immunodiffusion revealed antimitochondrial antibodies in 18 cases, whereas antibodies were not found in the other groups of patients, except for 1 case of systemic lupus erythematodes. ELISA demonstrated that in all 20 patients with primary biliary cirrhosis where immunofluorescence revealed antimitochondrial antibodies, there was an increase in the quantity of antibodies against mitochondrial inner membrane fractions, and in 7 cases even against the outer membrane fractions. These 7 were the most serious cases clinically. These methods allow the differentiation of antimitochondrial antibody subtypes and promote the establishment of the diagnosis. PMID- 2104970 TI - Frequency, tidal volume, and mean airway pressure combinations that provide adequate gas exchange and low alveolar pressure during high frequency oscillatory ventilation in rabbits. AB - We studied healthy and saline lavaged rabbits during high frequency oscillatory ventilation to determine what combination of frequency (f), tidal volume (Vt), and mean airway pressure (Paw) produced the lowest peak-to-peak alveolar pressure amplitude (Palv) and physiologic blood gas tensions. Sinusoidal volume changes were delivered through a tracheostomy by a piston pump driven by a linear motor. Tracheal pressure amplitude (Ptr) was measured through a tracheal catheter and alveolar pressure amplitude was measured in a capsule glued to the right lower lobe. PaO2, PaCO2, Ptr, and Palv were measured at the following settings: FiO2 = 0.5, frequency 2-28 Hz, Vt 1-3 mL/kg (50 150% dead space) and Paw 5-15 cm H2O. Many combinations of frequency and Vt resulted in the same PaO2 and PaCO2. Paw had a large effect on Palv and minimal effect on blood gas tensions. In lavaged rabbits, the composite variable f x Vt2 described the trends in Palv and blood gas tensions. As the product of f x Vt2 increased, PaO2 initially increased and then decreased, whereas PaCO2 decreased and Palv increased. No single combination of frequency, Vt and Paw simultaneously provided the lowest Palv and physiologic blood gas tensions. Adequate blood gas tensions and low Palv were obtained at frequencies less than 12 Hz, a Vt of 2 mL/kg and a Paw of 10 cm H2O. In healthy and lavaged rabbits PaO2 increased and PaCO2 decreased as frequency increased at lower Vt.PaO2 decreased as frequency increased at higher Vt in lavaged rabbits only. Palv tended to be greater in lavaged rabbits. PMID- 2104972 TI - Total body water measured by 18-O dilution and bioelectrical impedance in well and malnourished children. AB - Total body water (TBW) is an indicator of fat-free mass and thus of nutritional status but cannot be measured readily in children in developing countries who are at greatest risk of becoming malnourished. We therefore developed equations to predict 18O TBW from bioelectrical impedance (Z), wt, and ht in well and malnourished infants and children whom we considered characteristic of children evaluated in nutritional surveillances in Peru. Children 3 to 30 mo of age, whose wt were 3.4 to 14.4 kg, which was -2.8 to +1 SD wt-for-ht, were randomly assigned to group I (n = 30) to develop equations to predict TBW or to group II (n = 14) to cross-validate the predictive equations. Mean TBW measured by 18O dilution was 4.8 +/- 1.2 kg in group I, and 5.6 +/- 1.7 kg in group II. TBW ranged from 57 to 78% of body wt (65 +/- 6%) in group I and from 56 to 80% (64 +/- 6%) in group II, indicating no statistically significant differences in body composition. The following equation was developed and cross-validated: TBW, kg = 0.48 + 0.68 ht2/Z; standard error estimate = 0.36; r = 0.98). A slight improvement was achieved by the addition of body wt (TBW, kg = 0.76 + 0.18 ht2/Z + 0.39 wt; standard error estimate = 0.23; r = 0.99). PMID- 2104971 TI - Effect of lipoic acid in a patient with defective activity of pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, and branched-chain keto acid dehydrogenase. AB - Lactic acidosis and accumulation of 3-hydroxybutyrate and other citric acid cycle intermediates were found in an infant with a lethal syndrome of metabolic acidosis and renal tubular acidosis. Nevertheless, the patient was relatively well for 4 mo of life. The activity of the pyruvate dehydrogenase complex, 2 oxoglutarate dehydrogenase, and branched-chain keto acid dehydrogenase were all reduced to levels 9 to 29% of control. In contrast, the activity of lipoamide dehydrogenase was normal. The conversion of 1-14C-leucine and 1-14C-valine to 14CO2 and of U-L-14C-valine to its major metabolic product 3-hydroxyisobutyric acid by fibroblasts derived from the patient was less than 5% of control. Cultivation of the patient's fibroblasts in medium enriched with lipoic acid markedly improved these in vitro conversions of leucine and valine. PMID- 2104973 TI - Private health insurance of chronically ill children. AB - Accurate information regarding the adequacy of private health insurance coverage available to the families of chronically ill children is scarce. A national survey was conducted of firms offering health insurance to employees and their dependents. Data were collected concerning private health insurance coverage of services needed by chronically ill children, including basic medical care services, ancillary therapies, mental health services, and long-term care. Nearly all surveyed firms offered health insurance. Coverage of inpatient hospital care, outpatient physician services, medical supplies and equipment, x-ray studies, laboratory services, and prescription medications was widespread, but coverage of services such as physical therapy, speech therapy, occupational therapy, and nutrition services was much less prevalent. More than two thirds of the firms covered comprehensive home health services but often with limits and only in lieu of more expensive inpatient care. Long-term care, such as skilled nursing home care, was covered by only one third of firms. Overall, the survey results, combined with information concerning recent trends in private health insurance, reveal increasing coverage of lower cost alternatives to hospital or institutional care and improved maximum lifetime benefits and stop-loss coverage but also increased cost-sharing requirements. These results suggest that, although families with chronically ill children may have access to a widening range of services such as home health care or individual benefits management, they may be forced to bear an increasing proportion of the cost. PMID- 2104974 TI - Enterococcal sepsis in neonates: features by age at onset and occurrence of focal infection. AB - Fifty-six neonates with enterococcal septicemia in a single hospital from 1977 through 1986 were studied. The incidence was low and constant until 1983, when an increase, attributable to infections in infants older than 7 days of age (late onset), was noted. These infants were more premature (mean gestational age 29.5 vs 36.9 weeks) and had lower birth weights (mean 1250 vs 2700 g) than those with early-onset enterococcal sepsis, and in most the infections were characterized by a nosocomial origin. Infants with early-onset infection had a mild illness with respiratory distress typical of other etiologic agents or diarrhea without focal infection. By contrast, late-onset enterococcal sepsis was heralded by severe apnea, bradycardia, circulatory collapse, and increased ventilatory requirements. Focal infections, including scalp abscess or catheter-related infection (23% each), meningitis or pneumonia (15% each), were common. Rapid clinical improvement and clearance of bacteremia resulted from therapy with an aminoglycoside and either ampicillin or vancomycin, but only if abscesses were drained and intravascular catheters were removed. Mortality rates for early onset, late-onset, and necrotizing enterocolitis-associated infection were 6, 8, and 17%, respectively. Enterococcus is a frequent cause of late-onset septicemia in premature neonates, and empiric therapy should include appropriate antimicrobial agents. PMID- 2104975 TI - Fatal nonpowder firearm wounds: case report and review of the literature. AB - A previously unreported fatality due to a head wound from a CO2-powered BB pistol is described. In a review of the English language medical literature (primarily forensic), ten previous reports of fatality due to nonpowder firearms were found. A common mechanism is identified in the head wounds leading to fatality. Modern day technology has elevated the BB gun from toy to weapon. Often appearing trivial, BB and pellet gun injuries must be considered in the same class as those from small-caliber low-velocity powder firearms. A patient with a nonpowder firearm injury must be evaluated with a high index of suspicion for injuries that are not apparent during a general physical examination. PMID- 2104976 TI - Potential hazard of hypoalbuminemia in newborn babies after exchange transfusions with ADSOL red blood cell concentrates. PMID- 2104977 TI - Practical management of atrial fibrillation. AB - Management of atrial fibrillation includes assessing the need for rate control, identifying underlying conditions, and performing cardioversion or instituting long-term medical therapy. Elective cardioversion should be strongly considered for every patient, chiefly to decrease the incidence of embolic stroke. Patients who remain in chronic atrial fibrillation require attention to rate control; digoxin (Lanoxin) alone may be a poor choice if they are vigorous and active. Many subgroups of patients benefit from long-term anticoagulation. PMID- 2104978 TI - Spectroscopic studies of wild-type and mutant "zinc finger" peptides: determinants of domain folding and structure. AB - The "zinc finger" model [Miller, J., McLachlan, A. D. & Klug, A. (1985) EMBO J. 4, 1609-1614; Brown, R. S., Sander, C. & Argos, P. (1985) FEBS Lett. 186, 271 274] makes both specific structural and specific functional predictions about zinc finger consensus sequences that can be tested with a combination of genetic, molecular biological, and biophysical techniques. The yeast transcription factor ADR1 contains two adjacent zinc finger domains; genetic and deletion analyses showed that amino acid substitutions and deletions in the zinc finger domains resulted in the loss of protein activity. To test the structural and folding predictions of the zinc finger model, peptides encompassing each of the ADR1 fingers were synthesized (ADR1a and ADR1b) as well as a mutant finger peptide (del138) deleted for a single amino acid residue. The folding and metal-binding characteristics of these were assessed by 1H nuclear magnetic resonance (NMR) and visible spectroscopy. While a single unique conformational species was detected for the two wild-type peptides upon tetrahedral binding of zinc, the deletion peptide did not bind zinc with tetrahedral geometry, nor did it fold into a zinc finger domain. The metal-binding and folding results found with the mutant peptide were similar to those obtained when thiol alkylation or imidazole protonation of the wild-type peptides was performed. These data indicate that ligand spacing and both thiol and imidazole participation in zinc binding are specific and necessary requirements for zinc finger folding, which provides direct support for the initial predictions of the model. PMID- 2104979 TI - Active-site zinc ligands and activated H2O of zinc enzymes. AB - The x-ray crystallographic structures of 12 zinc enzymes have been chosen as standards of reference to identify the ligands to the catalytic and structural zinc atoms of other members of their respective enzyme families. Universally, H2O is a ligand and critical component of the catalytically active zinc sites. In addition, three protein side chains bind to the catalytic zinc atom, whereas four protein ligands bind to the structural zinc atom. The geometry and coordination number of zinc can vary greatly to accommodate particular ligands. Zinc forms complexes with nitrogen and oxygen just as readily as with sulfur, and this is reflected in catalytic zinc sites having a binding frequency of His much greater than Glu greater than Asp = Cys, three of which bind to the metal atom. The systematic spacing between the ligands is striking. For all catalytic zinc sites except the coenzyme-dependent alcohol dehydrogenase, the first two ligands are separated by a "short-spacer" consisting of 1 to 3 amino acids. These ligands are separated from the third ligand by a "long spacer" of approximately 20 to approximately 120 amino acids. The spacer enables formation of a primary bidentate zinc complex, whereas the long spacer contributes flexibility to the coordination sphere, which can poise the zinc for catalysis as well as bring other catalytic and substrate binding groups into apposition with the active site. The H2O is activated by ionization, polarization, or poised for displacement. Collectively, the data imply that the preferred mechanistic pathway for activating the water--e.g., zinc hydroxide or Lewis acid catalysis--will be determined by the identity of the other three ligands and their spacing. PMID- 2104980 TI - Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site. AB - Albumin Redhill is an electrophoretically slow genetic variant of human serum albumin that does not bind 63Ni2+ and has a molecular mass 2.5 kDa higher than normal albumin. Its inability to bind Ni2+ was explained by the finding of an additional residue of Arg at position -1. This did not explain the molecular basis of the genetic variation (since proalbumin contains adjacent Arg residues at -1 and -2) or the increase in apparent molecular mass. Fractionation of tryptic digests on concanavalin A-Sepharose followed by peptide mapping of the bound and unbound fractions and sequence analysis of the glycopeptides identified a mutation of 320 Ala----Thr. This introduces an Asn-Tyr-Thr oligosaccharide attachment sequence centered on Asn-318 and explains the increase in molecular mass. This, however, did not satisfactorily explain the presence of the additional Arg residue at position -1. DNA sequencing of polymerase chain reaction-amplified genomic DNA encoding the prepro sequence of albumin indicated an additional mutation of -2 Arg----Cys. This introduces a prepro sequence, Met Lys-Trp-Val-Thr-Phe-Ile-Ser-Leu-Leu-Phe-Leu-Phe-Ser-Ser-Ala-Tyr- Ser-Arg-Gly-Val Phe-Cys-Arg (cf.-Tyr-Ser-Arg-Gly-Val-Phe-Arg-Arg- in normal human pre proalbumin). We propose that the new Phe-Cys-Arg sequence in the propeptide is an aberrant signal peptidase cleavage site and that the signal peptidase cleaves the propeptide of albumin Redhill in the lumen of the endoplasmic reticulum before it reaches the Golgi vesicles, the site of the diarginyl-specific proalbumin convertase. PMID- 2104981 TI - Pseudomonas exotoxin contains a specific sequence at the carboxyl terminus that is required for cytotoxicity. AB - Pseudomonas exotoxin (PE), a single-chain polypeptide toxin of 613 amino acids, consists of three functional domains: an amino-terminal receptor-binding domain, a middle translocation domain, and a carboxyl-terminal ADP-ribosylation domain. Deletion of as few as 2 or as many as 11 amino acids from the carboxyl terminus of PE does not affect ADP-ribosylation activity but produces noncytotoxic molecules. Deletions and substitutions between positions 602 and 611 of PE show that the last 5 amino acids of PE are very important for its cytotoxic action. The carboxyl-terminal sequence of PE is Arg-Glu-Asp-Leu-Lys. Mutational analysis indicates that a basic amino acid at 609, acidic amino acids at 610 and 611, and a leucine at 612 are required for full cytotoxic activity. Lysine at 613 can be deleted or replaced with arginine but not with several other amino acids. Mutant toxins are able to bind normally to target Swiss mouse 3T3 cells and are internalized by endocytosis, but apparently they do not penetrate into the cytosol. A PE molecule that ends with Lys-Asp-Glu-Leu, which is a well defined endoplasmic reticulum retention sequence [Munro, S. and Pelham, R. B. (1987) Cell 48, 899-907], is fully cytotoxic, suggesting that a common factor may be involved in intoxication of cells by PE and retention of proteins in the lumen of the endoplasmic reticulum. Sequences similar to those at the carboxyl end of PE are also found at the end of Cholera toxin A chain and Escherichia coli heat-labile toxin A chain. PMID- 2104982 TI - Cytotoxic T-cell precursors with low-level CD8 in the diabetes-prone Biobreeding rat: implications for generation of an autoimmune T-cell repertoire. AB - Lymphocytes from diabetes-prone Biobreeding rats consistently fail to generate T cell-mediated cytotoxicity under conditions where cytotoxic T lymphocyte activity is readily demonstrated in normal rats. The failure is associated with generalized T-cell lymphopenia and marked reduction in the frequency of CD8+ cells. The few remaining CD8+ cells are widely held to be natural killer cells rather than class I major histocompatibility complex-restricted T lymphocytes. In this report we show that a detectable percentage of CD8+ lymphocytes express the T-cell receptor for antigen, thus identifying them as part of the T-cell lineage. The failure of these CD8+ T-cell-receptor-positive T cells to lyse target cells that are susceptible to T-cell mediated cytotoxicity is associated with markedly reduced expression of cell-surface CD8. Targets expressing higher than normal levels of class I major histocompatibility complex target antigen could be lysed, suggesting that reduction in CD8 has decreased T-cell activity for target antigen. We discuss the derivation of T cells that express low levels of CD8 and the role they could play in generating autoimmune diabetes. PMID- 2104983 TI - GTP-binding Ypt1 protein and Ca2+ function independently in a cell-free protein transport reaction. AB - The 21-kDa GTP-binding Ypt1 protein (Ypt1p) is required for protein transport from the endoplasmic reticulum to the Golgi complex in yeast extracts. Ypt1 antibodies block transport; this inhibition is alleviated by competition with excess purified Ypt1p produced in bacteria. Furthermore, extracts of cells carrying the mutation ypt1-1 are defective in transport, but transport is restored if a cytosolic fraction from wild-type cells is provided. The in vitro transport reaction also requires physiological levels of Ca2+. However, Ypt1p functions independently of Ca2+. First, buffering the free Ca2+ at concentrations ranging from 1 nM to 10 microM does not relieve inhibition by Ypt1 antibodies. Second, consumption of a Ca2+-requiring intermediate that accumulates in Ca2+ deficient incubations is not inhibited by anti-Ypt1 antibodies, although completion of transport requires ATP and an N-ethylmaleimide-sensitive factor. Thus, Ypt1p and Ca2+ are required at distinct steps. PMID- 2104984 TI - Neurons and glia arise from a common progenitor in chicken optic tectum: demonstration with two retroviruses and cell type-specific antibodies. AB - We used a recombinant retrovirus to study cell lineage in the chicken optic tectum. The virus inserts the Escherichia coli lacZ (beta-galactosidase) gene into the genome of an infected cell; a histochemical stain marks the progeny of infected cells with a blue precipitate. We had previously shown that individual clones frequently contain diverse neuronal types. Now we asked whether individual clones contain glia as well as neurons. To this end, we constructed a virus in which lacZ is fused to a nuclear localization signal sequence from the simian virus 40 large tumor antigen. Cells infected with this virus are marked with blue nuclei instead of blue somata. In embryos injected with a mixture of the two retroviruses, individual clusters contained cells with only one label type (nuclear or cytoplasmic), thus verifying that clusters of cells were clones. Furthermore, it was possible to immunostain the somata of cells that had blue nuclei, whereas the blue cytoplasmic precipitate hampered immunostaining. Together, these methods allowed us to show that some clones contained neurons (neurofilament-positive) and two types of glia (glutamine synthetase-positive and glial fibrillary acidic protein-positive). This result demonstrates the existence of a common progenitor for neurons and glia in optic tectum. PMID- 2104985 TI - Interleukin 5 is required for the blood and tissue eosinophilia but not granuloma formation induced by infection with Schistosoma mansoni. AB - Eosinophils are thought to play a major role in the immunobiology of schistosomiasis. To investigate the immunologic basis of the eosinophil response and directly assess the function of eosinophils in egg-induced pathology, mice infected with Schistosoma mansoni were injected with a monoclonal antibody produced against interleukin 5 (IL-5), a cytokine previously shown to stimulate eosinophil differentiation in vitro. This treatment suppressed the generation of eosinophil myelocyte precursors in the bone marrow and reduced to background levels the numbers of mature eosinophils in the marrow, in circulation, and within acute schistosome egg granulomas. Nevertheless, granulomas in the anti-IL 5-treated/eosinophil-depleted mice at 8 weeks of infection were only marginally smaller than those in animals injected with control monoclonal antibody, and hepatic fibrosis was comparable in the two groups. Additional parameters such as worm burden, egg output, and serum IgE levels were unaltered by the anti-IL-5 treatment. In contrast, infected animals injected with monoclonal antibody against gamma interferon (IFN-gamma) displayed circulating eosinophil levels that were elevated with respect to control mice, possibly because of an enhanced release of mature eosinophils from the marrow, and developed egg granulomas that were indistinguishable in size and cellular composition from those in control animals. Immunologic assays revealed that lymphocytes from acutely infected mice produce large quantities of IL-5 but minimal IFN-gamma when stimulated with either egg antigen or mitogen. Taken together, these results indicate that neither IL-5 nor eosinophils are essential for egg-induced pathology but suggest that lymphocytes that belong to the IL-5-producing TH2 subset predominate during acute infection and may induce granuloma formation by the production of other cytokines. PMID- 2104986 TI - Characterization of a class of nonformylated Enterococcus faecalis-derived neutrophil chemotactic peptides: the sex pheromones. AB - Bacteria produce a heterogeneous mixture of neutrophil chemotactic agents in culture filtrates. Formylmethionyl peptides have been shown to comprise a significant portion of the chemotactic activity in bacterial culture filtrates; however, not all of the chemotactic agents in bacterial culture filtrates are formylated peptides. To examine whether nonformylated peptides derived from bacteria could act as chemotactic agents, we studied several nonformylated hepta- and octapeptide Enterococcus faecalis-derived sex pheromones, their modified derivatives, and their competitive inhibitors for activation of rat peritoneal neutrophils. Several of these peptides, in particular cAM373 and cPD1, proved to be potent chemotactic agents in submicromolar concentrations as well as inducers of lysosomal granule enzyme secretion. Moreover, the more biologically active peptides were able to compete with fMet-Leu-[3H]Phe for binding to the formyl peptide receptor. These studies demonstrate that the formylmethionyl moiety may be an absolute requirement only for the binding of di- and tripeptides to the formyl peptide receptor. Larger peptides that may have or that may allow for additional contact points between the peptide and receptor may require N formylation only relatively. Indeed, by removing this structural restraint, the formyl peptide receptor may interact with an unlimited number of peptide fragments of both infectious and host origins to then modulate neutrophil responses to infection and inflammation. PMID- 2104987 TI - Acute reversal of flunitrazepam effects by Ro 15-1788 and Ro 15-3505: inverse agonism, tolerance, and rebound. AB - A phase 1 double blind crossover comparison of a new benzodiazepine antagonist (Ro 15-3505) with Ro 15-1788 and placebo, in the reversal of sedative and psychophysiological effects of single IV doses of flunitrazepam (2 mg), was carried out in 12 normal volunteers. The antagonists were equally effective, leading to full reversal of all effects with a potency ratio of approximately 2.5 mg Ro 15-1788 for 1 mg Ro 15-3505. Inverse agonism, in the form of unpleasant feelings and symptoms, was reported by all subjects following Ro 15-3505 but none after Ro 15-1788. Adaptational phenomena such as acute tolerance and rebound of sedative effects of flunitrazepam were also detected and their potential implications are discussed. PMID- 2104989 TI - Malignant external otitis: utility of CT in diagnosis and follow-up. AB - Malignant external otitis is a severe bacterial infection of the bone and soft tissues of the base of the skull that is frequently difficult to diagnose. The effectiveness of antibiotic therapy is likewise difficult to assess. Serial computed tomographic (CT) scans were obtained in 11 consecutive patients with malignant external otitis at time of diagnosis and periodically after conclusion of antibiotic therapy. All patients demonstrated abnormalities of the external auditory canal, with or without bone destruction. Soft tissue or fluid in the middle ear and mastoid, around the eustachian tube, and in the parapharyngeal space (both pre- and poststyloid) was seen in greater than 50% of the cases. While remineralization of bone was not seen, soft-tissue disease improved dramatically, and recurrence or persistence could be corroborated by detection of more extensive soft-tissue changes. By delineating the extra- and intracranial extent of disease, serial CT scans enable one to make the diagnosis, determine the extent of infection, document recurrence, exclude progression, and confirm resolution of malignant external otitis. PMID- 2104988 TI - TRH attenuates scopolamine-induced memory impairment in humans. AB - The brain tripeptide thyrotropin-releasing hormone (TRH) has been demonstrated to facilitate cholinergic neurotransmission. To test its interaction with the cholinergic system in humans, high-dose TRH (0.5 mg/kg) or placebo was administered intravenously (IV) to normal controls pretreated with scopolamine (0.5-0.75 mg IV), a centrally active muscarinic antagonist, which has been used to model aspects of the memory impairment of normal aging and of dementia. Compared to placebo, TRH markedly attenuated scopolamine-induced impairment of some measures of memory, most notably on a selective reminding task. This cognitive study is the first in humans to suggest a neuromodulatory effect of a peptide on the cholinergic system, and suggests a facilitatory role for TRH in human memory processes. PMID- 2104990 TI - Pulmonary embolism: segmental appearance of perfusion lung scan defects correlates with successful response to thrombolytic therapy. AB - Lung scan data from a series of 45 patients receiving thrombolytic therapy were reviewed to determine if any pattern on the pretherapy perfusion lung scans could be identified that predicted response to therapy. A segmental appearance on the pretherapy scans (complete or nearly complete absence of perfusion in a whole segment or a very large subsegment) was correlated with the amount of improvement in perfusion on lung scans obtained 24 hours after the start of thrombolytic therapy. As a group, patients with a segmental appearance on the pretherapy lung scans had more improvement in the perfusion reduction score than patients with a nonsegmental appearance (P less than .005). However, the correlation between segmental appearance and a favorable response to thrombolytic therapy was not strong enough to allow use of this appearance in the selection of patients for therapy. PMID- 2104991 TI - Renal eicosanoids. PMID- 2104992 TI - Flumazenil--a novel benzodiazepine antagonist. PMID- 2104993 TI - Controversies in thrombolysis--choice of the agent. PMID- 2104994 TI - Cardiovascular effects of anatoxin-A in the conscious rat. AB - The effects of anatoxin-A on mean arterial pressure (MAP), heart rate, cardiac index (CI), and blood flow (BF) in hindquarter (HQ), renal (R), and mesenteric (M) vascular beds were studied after intravenous (iv) and intracerebroventricular (icv) administration in the conscious rat. The pharmacological profile of anatoxin-A was further compared to nicotine administered iv and icv. MAP and heart rate were measured from femoral artery, CI by thermodilution method, and blood flow by Doppler velocimetry. Anatoxin-A and nicotine (30, 100 and 300 micrograms/kg iv) produced an increase in MAP with concomitant bradycardia. The highest doses increased CI. MBF and RBF decreased due to a vasoconstriction in M and R vasculature. These effects were attenuated by the ganglion blocker chlorisondamine (5 mg/kg, iv). Anatoxin-A (100 micrograms/kg, iv) increased plasma epinephrine levels by 2-fold with virtually no effect on norepinephrine whereas nicotine (100 micrograms/kg, iv) increased plasma epinephrine and norepinephrine by 20- to 30-fold. Central administration of anatoxin-A and nicotine (30-100 micrograms/kg icv) increased MAP with no effect on heart rate and produced M and R vasoconstriction. In summary, the present study demonstrates that anatoxin-A acts as a nicotinic cholinergic agonist in the conscious rat after both systemic and central administration. Anatoxin-A and nicotine produced pressor and reno-splanchnic vasoconstrictor responses and at high doses increased cardiac output. These effects were mediated by activation of the nicotinic receptors in the adrenal medulla and sympathetic ganglia. However, marked differences were found in the potency of anatoxin-A versus nicotine to stimulate the sympathoadrenomedullary axis. PMID- 2104996 TI - Effect of aflatoxin B1 treatment in vivo on the in vitro activity of hepatic and extrahepatic glutathione S-transferase. AB - The effect of aflatoxin B1 (AFB1) on the glutathione S-transferase activity (GST) and on non-protein thiol levels of different tissues was studied in adult male Wistar rats. Animals received a single dose of the toxin (100 or 500 micrograms/kg body wt., p.o.), and were studied 6 or 24 h after administration. GST was determined in liver, renal cortex, duodenum, jejunum-ileum and distal ileum, using 3 substrates: 1-chloro-2,4-dinitrobenzene (CDNB), trans-4-phenyl-3 buten-2-one (PBO) and 1,2-epoxyethylbenzene (STOX). The non-protein thiol content of all tissues tested increased with the lowest dose at 6 h, returning to normal values at 24 h, while the higher dose produced a significant decrease in reduced thiol levels at 6 h, returning to normal values at 24 h. AFB1 administration induced, independently of dose and tissue, total GST (CDNB) and epoxide transferase activity (STOX) while A--C-type transferases (PBO) were inhibited. Almost all activities returned to normal values at 24 h. In cases of enzyme induction there was in general an increase in Vmax and a decrease in apparent Km. The opposite was seen in cases of inhibition. In conclusion, the results provide evidence that extrahepatic GST could be important in the overall process of detoxification of AFB1. The behavior seen in hepatic and extrahepatic tissues revealed the functions of catalysis (B-type transferases) and covalent bond formation, as well as inactivation by probable AFB1 metabolites (A--C-type transferases). PMID- 2104995 TI - Dose-related induction of rat hepatic drug-metabolizing enzymes by diuron and chlorotoluron, two substituted phenylurea herbicides. AB - Dose-related induction of various hepatic drug-metabolizing enzymes has been investigated after short-term treatment of rats by diuron and chlorotoluron, a dichlorinated and a monochlorinated phenylurea herbicide, respectively. Results suggest that 'saturation' of the induction system of benzo(a)pyrene monooxygenase, 7-ethoxycoumarin O-deethylase and 7-ethoxyresorufin O-deethylase activities may occur in the same range of the molar doses of both compounds, and with the dichlorinated herbicide at much higher activities. Induction of epoxide hydrolase, UDP-glucuronyltransferase and glutathione S-transferases also shows saturation curves in the function of molar doses. However, the structural difference is not reflected in the enhancement of enzyme activities. PMID- 2104997 TI - Major histocompatibility complex markers and red cell antibodies to the Rh (D) antigen. Absence of association. AB - Between 20 and 35 percent of Rh(D) antigen-negative individuals do not develop antibodies to D even after multiple transfusions of Rh-positive red cells. To evaluate the possibility that antibody production after exposure to the D antigen was related to a major histocompatibility complex immune response gene, analysis of the HLA genotypes of 38 Rh-sensitized women and their families was performed. No significant deviations were found in the frequency of any individual HLA class I, II, or III allele or of any extended haplotype (fixed allelic combinations of HLA-B, HLA-DR, and the complement components BF, C2, C4A, and C4B). Type 1 errors due to the extreme allelic polymorphism of the HLA system, as well as the ethnic variation in patient groups, may have contributed to HLA allele-antibody responder relationships reported in earlier studies. PMID- 2104998 TI - A model for estimating incremental benefits and costs of testing donated blood for human immunodeficiency virus antigen (HIV-Ag). AB - We propose a model for estimating the benefit of adding a test for the human immunodeficiency virus antigen (HIV-Ag) to current procedures for testing donated blood. Using this model, data on HIV infection from published studies, and certain assumptions about blood donor behavior, we estimate that the probability of detecting an additional HIV-infective blood component is approximately 1 in 4,860,000. If this estimate is correct, adding HIV-Ag testing would prevent approximately 4 cases of primary transfusion-transmitted HIV infection annually in the United States. After adjustments for the median incubation period for AIDS, and for mortality due to primary illnesses, this estimate represents prevention of approximately 1 case of AIDS per year, within the 4 years after transfusion. A primary advantage of this model is its adaptability for recalculating cost-benefit analyses if more sensitive tests for HIV infection become available. In addition, we propose that comparing the anticipated costs and benefits of HIV-Ag testing to other possible uses of these funds should be an important factor in assessing the desirability of HIV-Ag testing. PMID- 2104999 TI - Alveolar soft part sarcoma: an electron microscopic study especially of uncrystallized granules using a tannic acid-containing fixative. AB - Electron microscopic observation of alveolar soft part sarcoma reveals crystalline structure as well as granules that are only partially composed of crystalloids. The uncrystallized part has been observed only as a dense amorphous substance by the conventional fixation method with glutaraldehyde or osmium tetroxide (or both). Some investigators have explained the uncrystallized areas as artifacts due to the fixation method and as being essentially crystallized; other investigators consider the dense amorphous material the prodromal state of crystallization. In this study, however, which used the fixation method most appropriate for the intracytoplasmic filaments (fixation in tannic acid containing glutaraldehyde and postfixation in osmium tetroxide) after increasing the permeability of the filaments to the fixative by pretreatment with a nonionic detergent (Triton X-100), the uncrystallized part was revealed to consist of an aggregation of many uncrystallized filaments with the same diameter (6 nm) as that of the crystallized filamentous structures. That is, the uncrystallized part was found to have been present as the prodromal state of crystallization and as filaments. PMID- 2105000 TI - [What is cost benefit analysis?]. AB - The practical and theoretical bases of cost-benefit analysis are reviewed systematically with particular emphasis on how an analysis can be carried out in practice. A Danish analysis about introduction of vaccination for mumps, measles and German measles is included as a common example. The great significance of elucidating the socio-economical questions to be answered before commencing an analysis is emphasized. It is therefore recommended that, among other things, as a side-effect of the actual cost-benefit analysis, a cash-analysis and a budget analysis should be carried out to identify the parties involved in the immediate expenses and incomes. This is particularly important in the cases where the same parties have a central position in the decision-making processes concerned in the project. In addition, costs and benefits are frequently distributed differently in time in different ways: Short-term expenses and long-term benefits. In connection with decision-making, this may also involve problems and should, therefore, be elucidated in detail. Similarly, the importance of including many alternatives in the analysis is emphasized and illustrated. In conclusion, it is demonstrated how well the theoretical principles have been followed, the employment and the process which led to the concrete analysis. PMID- 2105001 TI - Neuropeptide Y (NPY)-containing nerves in mammalian ureter. AB - The distribution of neuropeptide Y in the ureter of the rat, rabbit, and man has been determined by radioimmunoassay and chromatographic analysis of the tissue extract. The localization of neuropeptide Y-immunoreactivity has been identified by immunocytochemistry. A regional distribution of neuropeptide Y was found; highest concentrations being present in the ureterovesical junction. Throughout the ureter, neuropeptide Y-immunoreactive nerve fibers were identified to surround the blood vessels and a few plexuses of neuropeptide Y-containing nerves were present within the muscle layers. Neuropeptide Y was not present within ganglion cells. Treatment of rats with 6-hydroxydopamine resulted in a significant reduction of neuropeptide Y concentrations in the upper, middle, and lower thirds of the ureter. This depletion in extractable neuropeptide Y was associated with morphologic changes typical of axonal degeneration of the neuropeptide Y-containing nerve fibers. PMID- 2105002 TI - Economic considerations in management of complicated urinary tract infections. PMID- 2105003 TI - Retroviral integration in murine myeloid tumors to identify Evi-1, a novel locus encoding a zinc-finger protein. PMID- 2105004 TI - A note on concomitant immunity in host-parasite relationships: a successfully transplanted concept from tumor immunology. PMID- 2105005 TI - Hemostatic evaluation before abdominal interventions: an overview and proposal. PMID- 2105006 TI - Assessing hemostatic function before abdominal interventions. PMID- 2105007 TI - Imaging of pulmonary sequestration. PMID- 2105008 TI - Mediastinal lymph node enlargement on CT scans in patients with usual interstitial pneumonitis. AB - Usual interstitial pneumonitis (UIP) is a chronic pulmonary process with a characteristic peripheral fibrotic pattern on gross pathologic lung sections and CT scans. This condition is often idiopathic, but asbestosis, rheumatoid arthritis, and scleroderma may cause the same peripheral fibrosis in the lungs. UIP is associated with an increased incidence of pulmonary neoplasms. The purpose of this study was to evaluate the size of mediastinal lymph nodes in patients with UIP in whom no evidence was seen of malignancy or current active infection. CT scans of 14 patients (12 with idiopathic pulmonary fibrosis and two with collagen vascular disorders) were assessed for lymph node location (American Thoracic Society mediastinal map) and size. In 13 of 14 patients, nodes measured greater than threshold size values. Nodes as large as 20 x 30 mm were identified in three patients. Nodal sites 10R, 4R, 2R, 5, and 6 were most commonly abnormal. We conclude that increase in the size of mediastinal lymph nodes as shown on chest CT scans is common in patients with UIP, occurs without superimposed infectious or malignant complications, and is thus presumably part of the chronic inflammatory process. Consequently, lymphadenopathy in these patients does not suggest that they have lung cancer also. PMID- 2105009 TI - Cystic teratoma of the mediastinum: demonstration of fat/fluid level. PMID- 2105010 TI - A new device for evaluation of biopsy specimens of occult breast-lesions. PMID- 2105011 TI - Diagnostic quality of mammograms obtained with a new low-radiation-dose dual screen and dual-emulsion film combination. AB - We evaluated the image quality of mammograms made by using a new dual-screen, dual-emulsion film combination (Kodak Min-R Fast screen, T-Mat Mll film) that permits reduction of radiation exposure by approximately 50% when compared with a standard single-screen, single-emulsion film system (Kodak Min-R screen, OM-1 film). This new film has been improved when compared with earlier T-Mat M film, including the introduction of an inert dye to reduce light crossover to essentially 0%. Mammogram pairs made with the dual-emulsion film combination and the standard single-emulsion film combination were obtained in 50 patients otherwise undergoing routine mammography. The image pairs were randomized and evaluated by three radiologists who used a three-point scale (better, same, or worse). Each pair was evaluated with regard to parenchymal contrast, sharpness, and latitude, as well as the number and sharpness of calcifications (n = 19) and sharpness of masses (n = 12) when present. All three observers found the dual emulsion film combination to be better than or the same as the standard with regard to parenchymal sharpness (94-100%), the number and sharpness of calcifications (98-100%), and sharpness of masses (100%). Two observers found the dual-emulsion film combination to be significantly worse (p less than .05) than the standard with respect to parenchymal contrast (72%, 86%), and all three observers rated it significantly worse for film latitude (14 to 42%). Our results suggest that this new dual-emulsion film combination that allows mammography to be performed with less radiation exposure can be used without loss of image quality. PMID- 2105012 TI - Clinical and radiologic features of malignant neoplasms in organ transplant recipients: cyclosporine-treated vs untreated patients. AB - The radiologic and clinical features of 37 posttransplantation malignant tumors occurring in 33 organ transplant recipients were reviewed to determine the characteristics of the tumors, particularly in relation to previous treatment (or nontreatment) with cyclosporine. The 37 malignant tumors included lymphomas (eight in patients receiving cyclosporine and four in patients not given cyclosporine) and carcinomas of the skin and lips (11), head and neck (five), colon and rectum (three), uterus (two), vulva (two), lung (one), and urinary bladder (one). The neoplasms of the internal viscera and head and neck were relatively advanced when detected. The neoplasms of the skin, vulva, uterine cervix, and urinary bladder were low-grade malignant tumors. Most of the cyclosporine-induced malignant lesions were lymphomas. The lymphomas in cyclosporine-treated recipients were characterized by early appearance after transplantation; more extensive organ involvement; multiple, homogeneous solid lesions without central low density on CT and sonography; and regression after reduction of cyclosporine dose. We conclude that malignant tumors occurring after transplantation are often advanced and that lymphoma induced by cyclosporine has characteristic features. PMID- 2105013 TI - Sonographic diagnosis of perforation in patients with acute appendicitis. AB - The sonographic diagnosis of appendicitis can be challenging in patients with perforation. In order to detect the accuracy of specific sonographic features of appendiceal perforation, graded compression sonograms in 100 patients with surgically confirmed acute appendicitis were reviewed retrospectively. Twenty-two of these patients had perforation. A statistically significant association was found between three sonographic findings and perforation: loculated pericecal fluid, prominent pericecal fat, and circumferential loss of the submucosal layer of the appendix. No single finding had a specificity greater than 59%. By using a combination of one or more findings, the overall sensitivity of sonography for the diagnosis of perforation was 86%. The specificity, however, was only 60%. Our results suggest that in patients without a sonographically visible appendix, recognition of loculated pericecal fluid and prominent pericecal fat may be a useful indirect clue to the diagnosis of perforating appendicitis. PMID- 2105014 TI - Double-contrast enema: a simplified method for filling the colon. PMID- 2105015 TI - Limitations in the CT diagnosis of acute diverticulitis: comparison of CT, contrast enema, and pathologic findings in 16 patients. AB - Pitfalls in CT diagnosis of acute diverticulitis were investigated in 16 patients with the disease who had misleading or equivocal CT features. The CT appearance was correlated with contrast enemas (13 cases) and with surgical assessment and pathologic evaluation of resected specimens (12 cases). Limitations in the CT diagnosis were related to (1) marked thickening of the colonic wall, between 1 and 3 cm in cross section simulating colonic neoplasm (all patients); (2) inability to visualize small amounts of fibropurulent exudate in the absence of pericolic inflammatory changes (eight patients); (3) failure to detect discrete intramural abscess (five patients). Resected surgical specimens available in 12 cases proved that colonic wall thickening was caused by muscular hypertrophy and various degrees of submucosal inflammation, edema, fibrosis, or focal organized inflammatory tissue. Contrast enema was useful in 10 out of 13 patients by excluding carcinoma of the colon and confirming the diagnosis of acute diverticulitis. PMID- 2105016 TI - Gallstone extracorporeal shock-wave lithotripsy: time and treatment considerations. AB - We evaluated 30 gallstone lithotripsy procedures performed on 27 patients with the Dornier MPL-9000 Lithotripter to determine how time was spent in the lithotripsy suite and to evaluate the various technical reasons for interrupting the administration of shock waves during the treatment. The procedure averaged 98 +/- 32 min total time in the lithotripsy suite. This included an average of 22 +/ 6 min before the treatment, 70 +/- 28 min for administration of shock waves, and 6 +/- 2 min after the treatment. The time required to deliver the shock waves did not correlate with patient age, sex, or weight; the number of gallstones; or the number or date of the treatment. However, a trend was seen toward an association between shorter treatment times and larger stone volumes. On the average, the administration of shock waves was interrupted every 48 shock waves for various reasons. Electronically changing the imaging plane of the in-line sonographic transducer to retarget the stone in the focal zone was by far the most frequent reason for interrupting shock-wave delivery, averaging 56 shock waves between changes. We conclude that extracorporeal shock-wave lithotripsy of gallstones is a time consuming and technically demanding procedure that requires continuous monitoring and frequent interruption in order to optimize targeting and fragmentation of the stone(s) while maintaining the patient's comfort. PMID- 2105017 TI - The value of MR imaging in distinguishing leiomyomas from other solid pelvic masses when sonography is indeterminate. AB - The differentiation of a uterine leiomyoma from other solid pelvic masses on sonography is usually straightforward. Occasionally, the sonographic appearance of a pedunculated uterine leiomyoma may simulate that of a solid adnexal mass. The purpose of this study was to determine if MR imaging adds specificity to the diagnosis of indeterminate solid pelvic masses visualized with sonography. Nineteen patients were imaged with MR after sonography revealed the presence of a solid pelvic mass adjacent to the uterus but could not be used to determine whether the mass was a leiomyoma or some other type of tumor. The diagnostic criteria for a leiomyoma on MR imaging included (1) the presence of a mass adjacent to the uterus and (2) a mass that was predominantly low signal intensity or isointense compared with normal myometrium on T1-weighted images and predominantly low signal intensity on T2-weighted images. In 11 of 13 patients, the masses that met these MR criteria for leiomyoma were proved to be uterine leiomyomas at surgery. Another mass that met the criteria was shown to be a leiomyoma in the broad ligament; the other was an ovarian fibroma. Of the six cases that did not meet the MR criteria for the diagnosis of leiomyoma, three were proved to be degenerated fibroids, one was squamous cell carcinoma of the cervix, and two were ovarian malignant tumors. Because leiomyomas often have an MR appearance that is distinct from that of solid pelvic malignant tumors, MR imaging can be useful for the diagnosis of some indeterminate solid pelvic masses. PMID- 2105018 TI - Current status of adult uroradiology: a survey of members of the Society of Uroradiology. PMID- 2105019 TI - Pericaliceal varices due to the nutcracker phenomenon. PMID- 2105020 TI - Intratumoral fat in a renal oncocytoma mimicking angiomyolipoma. PMID- 2105021 TI - The frequency and diagnostic significance of periostitis in chondroblastoma. AB - A study was performed to determine the frequency of periosteal reaction associated with chondroblastoma, to investigate the underlying pathophysiology of the periosteal reaction, and to postulate the clinical importance of this radiographic observation. Two hundred fourteen histologically proved chondroblastomas were reviewed and observed for the presence or absence of periosteal reaction and for radiographic changes that might explain the cause of the periosteal reaction. A similar review was performed on 30 other epiphyseally centered lesions of various causes. A distinctive thick, solid periosteal reaction distal to the chondroblastoma was present in 47% of all chondroblastomas and 57% of chondroblastomas present in long bones (excluding the greater trochanter). No periosteal reaction was observed in any of the 30 epiphyseally centered lesions of other causes. When available for observation, plain films showed inflammatory changes in the joint surrounding the chondroblastoma, bone scintigraphy showed tracer uptake similar to that observed in inflammatory lesions and aggressive neoplasms, and MR images showed change in the marrow surrounding the chondroblastoma consistent with edema. This suggests an inflammatory reaction to the chondroblastoma, rather than mechanical stress across a weakened epiphysis, as the cause of the periostitis. We conclude that frequently the chondroblastoma produces a distinctive thick solid or layered periosteal response distant from the lesion along the diametaphyseal shaft. Observation of this unique periosteal response may help to distinguish chondroblastoma from other epiphyseally centered lesions. PMID- 2105022 TI - CT findings of degenerative arthritis of the atlantoodontoid joint. PMID- 2105023 TI - Diagnostic imaging of the temporomandibular joint: recommendations for use of the various techniques. PMID- 2105024 TI - Masses of the hand and wrist: detection and characterization with MR imaging. AB - To assess the value of MR imaging in the detection, delineation, and characterization of mass lesions of the hand and wrist, we reviewed the MR imaging findings of 38 patients referred for evaluation of such lesions. Twenty five patients had a palpable mass. In an additional 13 patients an occult mass lesion was suspected as the cause of distal ulnar neuropathy. Twenty-two mass lesions (16 benign and six malignant) were detected by MR. All were correctly predicted to be benign or malignant. In nine (56%) of the 16 benign mass lesions, the specific diagnosis was suggested. In the remaining seven benign mass lesions and in the six malignant tumors, the MR findings were not specific enough to permit a diagnosis. Of the 14 patients referred for evaluation of a distal ulnar neuropathy, an occult ganglionic cyst compressing the ulnar nerve was revealed with MR imaging in three. MR imaging of the hand and wrist is accurate in the detection of mass lesions and can correctly distinguish benign from malignant tumors in the majority of cases. Specific diagnoses can be made in certain benign lesions. Occult mass lesions can be confirmed or excluded as the cause of distal ulnar neuropathy with MR imaging. PMID- 2105025 TI - Scintigraphic findings in patients with shoulder pain caused by interleukin-2. AB - Interleukin-2 is receiving widespread interest as an immunotherapeutic agent in the treatment of certain cancers. Severe arthralgias recently have been reported as a significant side effect, and the cause of pain is unknown. Because interleukin-2 is an immune modulator, we reviewed the 99mTc-methylene diphosphonate scintigrams in nine patients who had developed shoulder arthralgias while receiving interleukin-2 for metastatic melanoma. In eight of the patients, the scintigrams showed diffuse increased uptake of radionuclide in the shoulders. Four patients had radiographs of their shoulders, all of which were normal. Bone scintigraphy in patients receiving interleukin-2 as immunotherapy for metastatic melanoma shows increased radionuclide activity in the shoulders. This process may relate to the role of interleukin-2 as a mediator in the inflammatory response. PMID- 2105026 TI - Spontaneous osteonecrosis of the knee: value of MR imaging in determining prognosis. AB - Sixteen patients with early and late stages of spontaneous osteonecrosis of the knee were studied to evaluate if MR imaging can be used to determine the prognosis of the disease. All patients had sequential conventional radiographs and clinical examinations, one or more 99mTc-methylene diphosphonate bone scintigrams, and an MR examination. The duration of the disease at the time of the MR examination ranged from 1 to 58 months (mean, 18 months). A relationship was identified between the pattern of bone marrow alteration noted on long TR/TE MR sequences and the scintigraphic stage and clinical course of the disease. The dimensions of the osteonecrotic region could be identified as well or better on the short TR/TE MR images than on the radiographs in all patients. MR imaging also afforded evaluation of the hyaline cartilage overlying the osteonecrotic lesion, revealing secondary osteoarthrosis in seven patients. We conclude that MR imaging in patients with spontaneous osteonecrosis of the knee may provide information of value for determining the prognosis of the disease. PMID- 2105027 TI - Is MR better than arthrography for evaluating the ligaments of the wrist? In vitro study. AB - The purpose of this study was to determine the relative merits of MR imaging and three-compartment digital arthrography in the assessment of carpal ligaments in vitro. We performed MR imaging and arthrography in 10 normal wrists of fresh cadavers ranging in age from 48 to 71 years, and compared the appearance of the interosseous ligaments and triangular fibrocartilage complex with findings on anatomic sections of the joints. In six of the specimens, relatively T1-weighted MR images, 800/20 (TR/TE), preceded three-compartment digital arthrography performed with standard contrast material. In the other four specimens, arthrography, using an MR solution of iodinated contrast material mixed with cupric sulfate and gelatin, was performed before MR imaging. This was done to mimic the intraarticular fluid that might be seen in an injured wrist. MR allowed accurate assessment of the triangular fibrocartilage complex and scapholunate ligament in eight of 10 cases. Consistent MR visualization of the lunotriquetral ligament was difficult. Three-compartment digital arthrography allowed accurate assessment of the triangular fibrocartilage complex and scapholunate and lunotriquetral ligaments in all 10 cases. We concluded that MR is useful but inferior to arthrography in the evaluation of interosseous ligaments and the triangular fibrocartilage complex. PMID- 2105028 TI - Imaging findings in a patient with pentazocine-induced myopathy. PMID- 2105029 TI - Ultrafast CT of laryngeal and tracheobronchial obstruction in symptomatic postoperative infants with esophageal atresia and tracheoesophageal fistula. AB - We evaluated the role of ultrafast CT in the diagnosis and follow-up of nine consecutive, symptomatic infants with suspected laryngeal and tracheobronchial obstruction after surgery for esophageal atresia. With 80% or more area collapse as a criterion for the diagnosis of laryngomalacia and 50% or more for tracheomalacia, six patients had tracheomalacia, one had laryngomalacia, and two had both. Tracheomalacia was focal in four patients and diffuse, involving the thoracic trachea, in the other four. Associated bronchomalacia was present in two patients. The site and degree of abnormality were verified by endoscopy in five of nine patients. The degree of tracheal collapse did not always correlate with the size of the esophageal pouch or with the site of the tracheo-esophageal fistula. These findings support the concept that the larynx and/or tracheal walls are often abnormal in symptomatic infants with esophageal atresia, tracheoesophageal fistula, and airway obstruction. Ultrafast CT was a reliable technique for detecting and assessing the site, extent, severity, and dynamics of airway collapse in five of seven symptomatic infants with congenital tracheoesophageal anomalies when the imaging findings were compared with endoscopic findings and previously published normal standards. PMID- 2105030 TI - Loculated intracranial leptomeningeal metastases: CT and MR characteristics. AB - Studies of twenty-five patients with loculated leptomeningeal tumor metastases diagnosed by CT and/or MR were analyzed retrospectively. Medulloblastoma was the most frequent primary tumor (8/25, 32%). Four subgroups of loculated patterns were identified. Type A included mass(es) limited to the subarachnoid space without obvious direct parenchymal infiltration; this pattern occurred in 12 patients, of whom five had associated diffuse pattern. Type B was characterized by mass(es) still predominantly in the subarachnoid space but with minor transpinal parenchymal infiltration; this pattern was found in five patients. Type C comprised subarachnoid mass(es) with marked transpinal extension mimicking parenchymal lesion; this pattern was observed in three patients. Type D consisted of subarachnoid mass(es) growing along the perineural CSF space; this pattern was noted in two patients. Additionally, two patients presented with combined A and C patterns, and one patient had a combined B and C pattern. More than half the patients (14/25, 56%) presented with a single lesion. The most frequent locations were the suprasellar cistern, ventricular walls, and lateral recesses of the fourth ventricle, Gd-DTPA-enhanced T1-weighted MR images appeared best for demonstrating the site and extent of disease. Recognition of the loculated patterns of leptomeningeal metastases, which are less common than the diffuse pattern, is important to radiologists and clinicians for correct diagnosis and proper management of patients with this disease. PMID- 2105031 TI - Reversal sign on CT: effect of anoxic/ischemic cerebral injury in children. AB - A retrospective study was performed to determine the clinical and pathologic features, etiology, and outcome of children with the reversal sign. The reversal sign, a striking CT finding, probably represents a diffuse, anoxic/ischemic cerebral injury. CT features of the reversal sign are diffusely decreased density of cerebral cortical gray and white matter with a decreased or lost gray/white matter interface, or reversal of the gray/white matter densities and relatively increased density of the thalami, brainstem, and cerebellum. Twenty children with the reversal sign were retrospectively analyzed. We divided the patients into three groups: (1) acute reversal, (2) intermediate group, and (3) chronic reversal. There were nine cases of trauma (seven of child abuse); nine hypoxia/anoxia incidents (birth asphyxia, drowning, status epilepticus); one bacterial meningitis; and one degenerative encephalitis. All acute- and intermediate-group patients had respiratory problems requiring ventilator support and intensive care. In five of seven patients who died, autopsy findings were consistent with anoxic/ischemic encephalopathy. Surviving patients have profound neurologic deficits with severe developmental delay. The CT reversal sign carries a poor prognosis and indicates irreversible brain damage. PMID- 2105032 TI - High-intensity basal ganglia lesions on T1-weighted MR images in neurofibromatosis. AB - Basal ganglia lesions, characterized on MR by increased signal intensity on T1 weighted images, were observed in seven patients with documented neurofibromatosis. These lesions most often involved the globus pallidus and internal capsules in a bilateral and symmetric fashion, and extended across the anterior commissure resulting in a "dumbbell" configuration. Smaller and less prominent foci of increased signal also were present on corresponding T2-weighted images. These lesions did not exhibit mass effect, edema, or enhancement with gadolinium-DTPA. They were not visible on CT (performed in two patients) and demonstrated no progression during a 2-year interval in three patients. Their signal characteristics and morphology suggest that they represent heterotopias containing Schwann cells and/or melanin deposits. Migrational abnormalities of these neural crest derivatives are known to occur in neurofibromatosis, and the presence of such heterotopias has been documented pathologically in patients with this disorder. While recent reports discuss foci of increased signal intensity on T2-weighted MR images in patients with neurofibromatosis, signal abnormalities on T1-weighted images have not yet been described. When lesions characterized by similar signal as well as morphologic characteristics are encountered on MR, the diagnosis of neurofibromatosis should be considered. PMID- 2105033 TI - Intraocular lesions in patients with systemic disease: findings on MR imaging. AB - Twenty-one intraocular lesions associated with various systemic diseases in 15 patients were studied by MR imaging. The disorders included diabetes mellitus, cardiovascular disease, Behcet disease, sarcoidosis, and ankylosing spondylitis. MR was performed on a 0.5-T system using a surface-coil technique. Ophthalmoscopic visualization of the fundus was precluded by the presence of opaque media in all cases. MR was found to be effective in demonstrating intraocular bleeding, vitreous opacity, detached lesions of the posterior pole, and eyeball deformity. Surface-coil MR is a useful adjunct in the evaluation of the eyes affected by systemic diseases, especially in patients with opaque media. PMID- 2105034 TI - Coloboma: evaluation with real-time sonography. PMID- 2105035 TI - Color Doppler imaging of portosystemic shunts. AB - This study was designed to investigate the utility of color Doppler sonography in the evaluation of portosystemic shunts. Thirty-one patients with a total of 32 shunts were imaged. The types of shunts examined included portacaval, five; mesocaval, eight; distal splenorenal (Warren), 14; and mesoatrial, five. Sonography was performed without knowledge of the status of the shunt, although the type of shunt was known before beginning the study. The sonographic studies were evaluated to determine their sensitivity and specificity on the basis of a prospective comparison with angiography or MR imaging (22 cases). The possible advantages of color Doppler over duplex Doppler sonography in evaluating portosystemic shunts were also investigated, as was the ability of color Doppler sonography to image specifically the shunt anastomoses. Color Doppler sonography successfully inferred shunt patency (17 cases) or thrombosis (five cases) in all 22 shunts for which correlative imaging was available (sensitivity = 100%, specificity = 100%). In comparing duplex with color Doppler sonography in all 32 shunts, the two techniques were almost equally effective in establishing patency in portacaval, mesocaval, and mesoatrial shunts. Duplex Doppler sonography, however, provided useful diagnostic information in only four of 14 splenorenal shunts. Color Doppler correctly inferred patency or thrombosis in all 14. Among all 32 shunts, the anastomosis was shown clearly by color Doppler in 23, probably in four, and not all in five. Our results suggest that color Doppler sonography is an excellent method for the evaluation of all varieties of surgically created portosystemic shunts. In particular, color Doppler sonography appears to be superior to duplex Doppler sonography in imaging splenorenal communications. PMID- 2105036 TI - Invasion of the carotid artery and jugular vein by lymph node metastases: detection with sonography. AB - Knowledge of invasion of the walls of the cervical vessels by tumor is of great clinical importance before surgery. We performed sonography on 83 patients with palpable cervical lymph node metastases in the region of the carotid bifurcation to determine the relationship of the metastases to the carotid artery and jugular vein. In all patients, the sonographic results were proved by surgery. The wall of the carotid artery was hypo-echogenic in 11 of 12 patients with surgically proved tumor invasion of the artery. Four results were false-positive. Palpation or swallowing during real-time scanning showed mobility of the tumor relative to the wall of the artery in 47 patients (57%). In these patients, tumor invasion could be excluded. Bilateral compression or invasion of the internal jugular vein was identified correctly with sonography in all five patients in whom this was confirmed surgically. These results suggest that real-time sonography is a valuable method for determining the relationship between cervical lymph node metastases and the carotid artery and jugular vein. PMID- 2105037 TI - Picture archiving and communication systems in Japan: 3 years later. PMID- 2105038 TI - Sensitivity of mammography. PMID- 2105039 TI - Lingual cortical defect of unknown cause. PMID- 2105040 TI - Double-J catheter for transgastric cystogastrostomy. PMID- 2105041 TI - Retention of contrast material in focal nodular hyperplasia of the liver on delayed CT: another case. PMID- 2105042 TI - An unusual case of hepatic hemangiomatosis: sonographic, CT, and 99mTc-RBC findings. PMID- 2105043 TI - Trichilemmal cyst of the scalp: MR imaging. PMID- 2105044 TI - CT diagnosis of traumatic mesenteric venous thrombosis. PMID- 2105045 TI - Entrapment of the popliteal artery: MR findings. PMID- 2105046 TI - Simple method to identify sequential images. PMID- 2105047 TI - Modification of experimental and clinical atherosclerosis by dietary fish oil. AB - A number of experimental studies have reported that dietary fish oil can attenuate the development of atherosclerosis in cholesterol-fed rats, quails, rabbits, pigs, and monkeys. Epidemiologic studies suggest that dietary fish oil can reduce the development of cardiovascular disease in humans. Data are limited but suggest that laboratory animals, normal volunteers, and patients with hyperlipidemia show similar responses to the consumption of fish oil. The major effect of dietary fish oil on serum lipoproteins is a reduction in plasma triglyceride levels, with inconsistent effects on plasma cholesterol and HDL cholesterol. Dietary fish oil induces a significant reduction of platelet aggregation associated with a prolonged bleeding time. This antithrombotic effect may be partially related to a decreased thromboxane A2 and to an increased prostacyclin level. Dietary fish oil may also have anti-inflammatory and anti immunologic effects through an elevation of prostaglandins and a reduction in the level of leukotriene B4. Recent experimental data suggest that either fish oil or verapamil can bring on a regression in atherosclerosis in cholesterol-fed rabbits put on a normal diet; however, there was no additive effect of the combination of these agents. Overall, data suggest that fish oil may have a role in attenuating the development of atherosclerosis. PMID- 2105048 TI - Echocardiographic evaluation of segmental wall motion early and late after thrombolytic therapy in acute myocardial infarction: the Western Washington Tissue Plasminogen Activator Emergency Room Trial. AB - In 92 acute myocardial infarction (AMI) patients treated with tissue plasminogen activator 2.3 +/- 1.2 hours after the onset of chest pain, echocardiography was performed at 11 +/- 14 hours (early) and, in 49 patients, again at 13 +/- 7 weeks (late). Infarct location and the left ventricular wall motion score index--the average score (normal = 1, hypokinetic = 2, akinetic = 3, dyskinetic = 4) for 20 segments--were determined by 2 observers unaware of clinical, angiographic or electrocardiographic data. Concordance between noninvasive infarct location by electrocardiography or echocardiography and infarct-related artery at angiography 4 +/- 2 days later (n = 85) was 76 and 81%, respectively. The early wall motion score index was worse for anterior (1.8 +/- 0.4) versus inferior (1.3 +/- 0.2, p less than 0.0001) or posterior-lateral (1.6 +/- 0.2, p = 0.0003) infarcts. Overall, the wall motion score index improved from early to late echocardiography (n = 49, 1.5 +/- 0.3 to 1.3 +/- 0.3, p = 0.0008). However, improvement was confined to those with time to treatment less than or equal to 2 hours (n = 22, 1.4 +/- 0.3 to 1.2 +/- 0.2, p less than 0.0001), and evidence of reperfusion at angiography (n = 38, 1.5 +/- 0.3 to 1.2 +/- 0.3, p less than 0.0001). The decrease in the wall motion score index was related to a decrease in the number of adjacent involved segments (5.5 +/- 3.0 to 3.7 +/- 3.9/patient, p = 0.0006). Thus, echocardiography early after AMI identifies infarct location. Improvement in regional wall motion is seen after early treatment with intravenous tissue plasminogen activator. PMID- 2105049 TI - The Cardiac Arrhythmia Suppression Trial: background, interim results and implications. AB - The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular premature complexes (VPCs) in survivors of acute myocardial infarction would reduce arrhythmic death risk. Instead, a preliminary finding from the CAST was that the encainide and flecainide groups had a 3.6-fold increase in arrhythmic death compared with their placebo group. These unfortunate results were especially surprising in that the CAST population represented patients in whom the risk of arrhythmic death was only moderate and the risk of proarrhythmia was thought to be low. In contrast, the arrhythmic death rate of the CAST placebo group was unusually low, to the extent that it paralleled the arrhythmic death rate in previous clinical trials of patients surviving myocardial infarction with no ventricular arrhythmia. The excessive arrhythmic death rate in patients taking encainide and flecainide occurred over the duration of the CAST, implying a proarrhythmic effect that may be due to mechanisms that are unique in this population, and thus challenging traditional concepts of proarrhythmia. The existing knowledge regarding the proarrhythmic and negative inotropic effects of encainide and flecainide are reviewed. The previous pharmaceutical database experience with these 2 antiarrhythmic drugs exceeded 3,000 patients; however, there was no indication of this serious proarrhythmic effect. In contrast, the CAST population taking encainide and flecainide totaled only 725 patients who were followed for 10 months and had an extremely high proarrhythmic event rate. The reasons for this discrepancy are discussed. The results of the CAST emphasize the power of a randomized, placebo-controlled clinical trial to uncover previously unsuspected benefits or liabilities of traditional therapies. PMID- 2105050 TI - Clinical implications of new studies in the treatment of benign, potentially malignant and malignant ventricular arrhythmias. AB - For purposes of clinical management, ventricular arrhythmias have been divided into risk categories of benign, prognostically important (potentially malignant) and malignant. Benign arrhythmias occur in the setting of structurally normal hearts and do not require therapy unless associated with debilitating symptoms. Malignant arrhythmias such as sustained ventricular tachycardia or fibrillation deserve aggressive therapy to prevent recurrence. Arrhythmias occurring in the presence of organic heart disease (often ischemic disease) are frequently asymptomatic but prognostically important as a risk factor for sudden death or cardiac arrest. The common empiric practice to treat such arrhythmias (by about 40 to 50% of cardiologists in the United States) needs to be reassessed in the face of the Cardiac Arrhythmia Suppression Trial. For malignant arrhythmias, class IA agents (procainamide and quinidine) continue to be the standard of treatment, and class IB agents (e.g., mexiletine) may be used as alternative or additive therapy. Class IC agents are used as second-line therapy, especially in the setting of ischemic heart disease. Class III therapy with amiodarone is reserved for refractory patients because of potential toxicity. Sotalol, a new class II-III agent, may become a first-line drug. For prognostically important arrhythmias, beta blockers remain the agents of choice, class IC agents are contraindicated, and class IA or IB drugs, or both, should be used conservatively (i.e., only for symptomatic arrhythmias). For symptomatic but benign arrhythmias requiring treatment, beta blockers are safe although not always effective. Class IA, IB and IC agents may then be considered. In these patients, the proarrhythmic potential of quinidine and class IC agents remains a concern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105051 TI - Comparative distribution of carbonic anhydrase isozymes III and II in rodent tissues. AB - Carbonic anhydrase (CA) III was demonstrated immunocytochemically in epithelium in some regions of salivary gland ducts, colon, bronchi, and male genital tract and in adipocytes, in addition to skeletal muscle and liver where the isozyme was previously localized. Basal cells beneath the submandibular gland's excretory ducts in guinea pig stained for CA III. Carbonic anhydrase III occurred alone in some and with CA II in other sites but was often absent from CA-II-containing types of cells. This was exemplified by CA III's abundance in CA-II-positive proximal colon and its sparsity in the CA-II-rich distal colon of the mouse. Striated ducts in guinea pig, but not mouse salivary glands, stained darker for CA and appeared accordingly to function more actively in ion transport compared with excretory ducts. Carbonic anhydrase content varied among genera in liver and pancreas and between mouse species and strains in salivary glands and kidney. Newly observed murine sites of CA II activity included Auerbach's plexus and a population of leukocytes infiltrating the lamina propria in small intestine, and several types of cells in the male genital tract. In immunoblot tests, antisera to CA III showed no cross reactivity with antisera to CA II, but those to CA II disclosed weak cross reactivity with CA III. PMID- 2105052 TI - Comparison of substrate utilization by indirect calorimetry during cyclic and continuous total parenteral nutrition. AB - Five male adult home patients were studied in a randomized order under continuous (24 h/d) and nocturnal cyclic (15 h/d) isocaloric, isonitrogenous total parenteral nutrition (TPN). They received 2626 +/- 265 total kcal/d as 60% dextrose and 40% lipids; the 3-h lipid infusion was followed by the dextrose amino acid infusion on both regimens. Substrate oxidation was measured by indirect calorimetry during four periods on the fourth day of each regimen. During cyclic TPN net lipogenesis occurred with a nonproteic respiratory quotient (npRQ) greater than 1 during dextrose amino acid infusion followed by net lipolysis with an npRQ less than 1 during the nonnourishing phase. In contrast, during continuous TPN net lipogenesis persisted with an npRQ greater than 1 over the 21 h of dextrose amino acid infusion. During the 3-h lipid infusion, fat oxidation was observed during both regimens but was more pronounced during cyclic TPN (p less than 0.05). As a consequence, 24-h lipid oxidation was higher and 24 h dextrose utilization lower during cyclic vs continuous TPN (p less than 0.05). These results suggest that cyclic TPN when alternating between substrate storage and oxidation, mimics the physiological pattern of oral feeding. PMID- 2105053 TI - Influence of dietary lipids on serum apoproteins AI and B and on intestinal synthesis of apo AI in the early weaning of piglets: comparison of saturated, unsaturated, and medium-chain triglycerides. AB - Early weaning of piglets induces a rapid decrease in the concentration of all plasma lipoproteins within 2 d. The decline was more progressive when 20% saturated fatty acid (lard) (SF) was added to the diet; saturated fatty acid was more effective than unsaturated fatty acid (sunflower oil) (UF). Medium-chain triglycerides had no protective effect. Intestinal synthesis of apoprotein AI was twofold higher in preweaning piglets than in adults (12.9% of total synthesis vs 5.9%, p less than 0.01) when measured in intestinal mucosa. On day 4 of weaning, synthesis was still at the preweaning level in all groups but on day 7 was maintained only by the SF diet (11.7%). We conclude that long-chain lipids, particularly saturated fatty acids, prevent a decrease in lipoproteins at weaning, mainly by maintaining intestinal apo AI synthesis at a high level. PMID- 2105055 TI - Hydroxy- and hydroperoxy-6,8,11,14-eicosatetraenoic acids induce sister chromatid exchanges in cultured mammalian cells. AB - Oxygen radical-induced genetic damage may be mediated by products of lipid peroxidation, in particular, arachidonic acid. Several isomeric hydroxy- and hydroperoxy-6,8,11,14-eicosatetraenoic acids (HETEs and HPETEs), intermediates of arachidonic acid metabolism, were evaluated for their ability to cause sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells. Both HETEs and HPETEs induced SCEs in a dose-dependent fashion at concentrations of 5, 10, and 20 microM. At each concentration, HETEs were more effective in producing SCEs than the corresponding HPETEs. Each of the isomeric forms used were equally effective in producing genetic damage. Antioxidants (superoxide dismutase, catalase and mannitol) were protective suggesting an intermediate role for the hydroxyl radical. Iron chelation by desferrioxamine suppressed SCE induction by 45% and an additional 33% inhibition was observed upon the addition of the calcium chelator EGTA. PMID- 2105054 TI - Comparative absorption of [13C]glucose and [13C]lactose by premature infants. AB - Oxidation of orally administered [13C]glucose and [13C]lactose and fecal recovery of malabsorbed substrates were determined in two groups of premature infants. Eighteen studies were performed with six infants at Johns Hopkins Hospital (JHH); 24 studies were performed with nine infants at Columbus Children's Hospital (CCH). The two groups differed in that JHH infants had shorter gestations but were older when studied. Fecal 13C loss after [13C]glucose administration did not differ between the two groups. Compared with glucose, the metabolism of lactose appeared to involve more malabsorption and colonic fermentation in JHH infants than in CCH infants and resulted in higher fecal losses of substrate carbon. Maturation appeared to involve increased proximal intestinal absorption and greater retention of absorbed carbohydrate. Simultaneous absorption of substrate from the small and large intestine may limit the usefulness of breath tests for 13C in the premature infant. PMID- 2105056 TI - Granular epithelial keratopathy as an unusual manifestation of Pseudomonas keratitis associated with extended-wear soft contact lenses. AB - We describe four patients who, using extended-wear soft contact lenses for myopia, abruptly developed ocular irritation and injection associated with elevated granular opacities initially confined to the central corneal epithelium. Cultures of the granular epithelial lesions were positive for Pseudomonas aeruginosa in all patients. Cultures of the contact lenses and lens case solutions grew Pseudomonas species and other gram-negative organisms. All patients responded to discontinuation of lens wear and frequent topical antibiotics. All recovered baseline visual acuity, and three have successfully resumed contact lens wear. These cases document that Pseudomonas keratitis may be manifested as a granular epithelial keratopathy. PMID- 2105057 TI - Dilution and storage of recombinant tissue plasminogen activator (Activase) in balanced salt solutions. PMID- 2105058 TI - A murine model of mucopolysaccharidosis VII. Gross and microscopic findings in beta-glucuronidase-deficient mice. AB - This report describes the clinical and pathologic alterations found in mice that have a recessively inherited, essentially complete deficiency of the lysosomal enzyme beta-glucuronidase. Affected animals have a shortened life span and are dysmorphic and dwarfed. Abnormal gait and decreased joint mobility correlate with glycosaminoglycan accumulation in articular tissue and cartilaginous and bony lesions result in extensive skeletal deformation. In these enzyme-deficient animals, lysosomes, distended by fine fibrillar and granular storage material, are particularly prominent in the macrophage system but also occur in other tissues including the skeletal and central nervous systems. The clinical and pathologic abnormalities in these mutant mice closely parallel those identified in humans with mucopolysaccharidoses (MPS). Therefore, these mice provide a well defined genetic system for the analysis of the pathophysiology of mucopolysaccharidosis type VII, which has many features in common with the other MPS. The mutant mice provide an attractive animal model to test potential therapies for lysosomal storage disease. PMID- 2105059 TI - Interleukin-1 alpha inhibits the effects of gamma-interferon and tumor necrosis factor alpha on the expression of the major histocompatibility antigens by the rat endothelium. AB - Modulation of the major histocompatibility (MHC) antigen expression on rat endothelial cells by a mixture of cytokines has been examined. Experiments were performed employing both enzyme-linked immunoassay (ELISA) and fluorescence activated cell-sorting (FACS) techniques and recombinant cytokines: interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and gamma-interferon (tau IFN). The results obtained show that TNF alpha enhances the effect of tau IFN on the expression of class I and II MHC antigens. IL-1 alpha did not affect tau IFN-induced class I expression but did inhibit tau IFN-induced class II expression. Finally, TNF alpha-induced class I MHC expression was inhibited strongly by IL-1 alpha. Pretreatment of endothelium with tau IFN did not potentiate the effects of IL-1 alpha or TNF alpha on the endothelial MHC antigen expression. These results suggest a possible anti-inflammatory role of IL-1 alpha via down-regulation of MHC antigen expression by the endothelium. PMID- 2105061 TI - Anesthetic implications of Zenker's diverticulum. PMID- 2105060 TI - Hairy cell leukemia-associated antigen LeuM5 (CD11c) is preferentially expressed by benign activated and neoplastic CD8 T cells. AB - LeuM5 antigen (CD11c, p150.95) expression, widely used as an immunodiagnostic marker for B-cell hairy cell leukemia, was examined on benign, normal peripheral blood T cells before and after stimulation in vitro with phytohemagglutinin and on a large, diverse panel of 73 T-cell neoplasms. Resting T cells lacked LeuM5. Intracytoplasmic LeuM5 was detectable at 3 to 4 days and surface membrane LeuM5 was detectable continuously between 5 and 17 days on greater than or equal to 20% CD3 cells (maximum, 42% CD3 cells at 10 days) after activation. Two-color flow cytometric analysis of the activated T cells demonstrated that a maximum of 60% CD8 but only 25% CD4 cells expressed LeuM5; the mean percentage of LeuM5+ CD8 cells was 44% compared with 12% LeuM5+ CD4 cells. A variable proportion of the neoplastic T cells in 19 of 73 (26%) T-cell neoplasms were LeuM5+. Twelve of 18 CD4-CD8+ (67%) but only 5 of 40 CD4+ CD8- T-cell neoplasms expressed LeuM5. These studies demonstrate that the LeuM5 antigen is 1) expressed in association with T cell activation, 2) preferentially expressed by activated CD8 cells, and 3) variably expressed by neoplastic T cells, but particularly by those exhibiting the CD4- CD8+ phenotype. PMID- 2105062 TI - Flumazenil and hypoxic ventilatory response. PMID- 2105063 TI - On the water produced when CO2 reacts with soda lime. PMID- 2105064 TI - The rate of CSF formation, resistance to reabsorption of CSF, and aperiodic analysis of the EEG following administration of flumazenil to dogs. AB - The effects of flumazenil, a benzodiazepine antagonist, on the rate of cerebrospinal fluid (CSF) formation (Vf), resistance to reabsorption of CSF (Ra) and the electroencephalogram (EEG) was determined in 12 dogs anesthetized with halothane (0.4%, end-expired) and nitrous oxide (66%, inspired) in oxygen. In six dogs the responses to flumazenil were measured during administration of midazolam (1.6 mg/kg followed by 1.25 mg.kg-1.h-1, intravenously) given along with inhalational anesthesia, whereas in the other six dogs the responses to flumazenil were measured during inhalational anesthesia without midazolam. Vf and Ra were determined using ventriculocisternal perfusion, and EEG activity was evaluated using aperiodic analysis. Flumazenil, 0.0025 and 0.16 mg/kg, was administered both when CSF pressure was normal and when CSF pressure was increased to 36-38 cmH2O by continuous infusion of mock CSF. Flumazenil produced no statistically significant change in Vf. Flumazenil did produce inconsistent and relatively small changes in Ra. Quantitative aperiodic analysis indicated changes in EEG activity only when the larger dose of flumazenil was given to dogs receiving midazolam. At normal CSF pressure the changes were consistent and were comprised of decreases in theta, alpha, and total hemispheric power. At elevated CSF pressure the changes were less consistent. It is concluded that smaller doses of flumazenil (which cause no EEG changes with the present method of analysis) and larger doses of flumazenil (which reverse midazolam-induced increase of theta and alpha activity) produce no change of Vf and no consistent change of Ra. Although flumazenil given in the presence of midazolam may increase Ra, thereby increasing CSF pressure and impairing contraction of CSF volume, this effect is not likely to be clinically important. PMID- 2105065 TI - Fiberoptic intubation complicated by pulmonary edema in a 12-year-old child with Hurler syndrome. PMID- 2105066 TI - Capnography or capnometry? PMID- 2105068 TI - PaCO2 management during cardiopulmonary bypass: intriguing physiologic rationale, convincing clinical data, evolving hypothesis? PMID- 2105067 TI - Contribution of prostacyclin to D-tubocurarine-induced hypotension in humans. AB - In order to evaluate the role of prostacyclin in d-tubocurarine-induced hypotension in human, the authors examined the relationship of changes of arterial blood pressure and plasma 6-keto-PGF1 alpha level following iv administration of d-tubocurarine (dTc), with or without prior administration of aspirin and H1 antagonist. The bolus injection of dTc 0.6 mg/kg caused a significant decrease in mean arterial pressure (MAP) that was associated with a significant increase in plasma 6-keto-PGF1 alpha (P less than 0.05 in both). The maximum MAP decrease and plasma 6-keto-PGF1 alpha increase were noted at 2 min after dTc administration. Pretreatment with aspirin DL-lysine (25 mg/kg) or diphenhydramine (1 mg/kg) significantly attenuated the responses of MAP (P less than 0.05 in both) and plasma 6-keto-PGF1 alpha level (P less than 0.01 for aspirin group, P less than 0.05 for diphenhydramine group). There was a significant correlation between the changes in plasma 6-keto-PGF1 alpha and those in MAP (Kendall tau (tau) = -0.504, P less than 0.01). These findings suggest that a bolus injection of dTc induces a release of prostacyclin through H1 receptor, which is responsible for the dTc-induced transient decrease of blood pressure in humans. PMID- 2105069 TI - Photodeactivation of ethyl violet: a potential hazard of Sodasorb. AB - Breathing circuit cannisters containing functional CO2 absorbent are critical to prevent rebreathing CO2 during general anesthesia using closed or semiclosed breathing systems. Ethyl violet is the indicator dye added to Sodasorb to indicate impending exhaustion of the absorbent. A case of CO2 rebreathing due to failure of ethyl violet indicator in exhausted Sodasorb was encountered. Laboratory investigation demonstrated that dye failure could result from photodeactivation caused by fluorescent lights. Using a fixed intensity fluorescent light source and quantitative spectrophotometric analysis, a highly significant dose-response relationship was demonstrated between duration of light exposure and the decrease in ethyl violet concentration. After 24 h of fluorescent light exposure with a received flux density of 46 nwatts/cm2 at 254 nm, the concentration of functional ethyl violet remaining in pulverized Sodasorb was 16% of the baseline value. Furthermore, using multiple light sources of various intensities, the greater the intensity of light, the more rapid the rate of decline of the ethyl violet concentration. It is recommended to minimize the problem by using ultraviolet filters and incorporating additional ethyl violet in Sodasorb. Finally, ethyl violet undergoes temporal deactivation after a Sodasorb container is opened, even if it is stored in the dark. PMID- 2105070 TI - A randomized study of carbon dioxide management during hypothermic cardiopulmonary bypass. AB - Eighty-six patients undergoing coronary artery bypass graft (n = 63) or intracardiac (n = 23) surgery were randomly assigned with respect to the target value for PaCO2 during cardiopulmonary bypass. In 44 patients the target PaCO2 was 40 mmHg, measured at the standard electrode temperature of 37 degrees C, while in 42 patients the target PaCO2 was 40 mmHg, corrected to the patient's rectal temperature (lowest value reached: mean 30.1, SD 1.9 degrees C). Other salient features of bypass management include use of bubble oxygenators without arterial filtration, flows of 1.8-2.4 l.min-1.m-2, mean hematocrit of 23%, and mean arterial blood pressure of approximately 70 mmHg, achieved by infusion of phenylephrine or sodium nitroprusside. Neuropsychologic function was assessed with series of tests administered on the day prior to surgery, just before discharge from the hospital (mean 8.0, SD 5.8 days postoperatively, n = 82), and again 7 months later (mean 220.7, SD 54.4 days postoperatively, n = 75). The scores at 8 days showed wide variability and generalized impairment unrelated to the PaCO2 group or to hypotension during cardiopulmonary bypass. At 7 months no significant difference was observed in neuropsychologic performance between the PaCO2 groups. Regarding cardiac outcome, there were no significant differences between groups in the appearance of new Q-waves on the electrocardiogram, the postoperative creatine kinase-MB fraction, the need for inotropic or intraaortic balloon pump support, or the length of postoperative ventilation or intensive care unit stay. These findings support the hypothesis that CO2 management during cardiopulmonary bypass at moderate hypothermia has no clinically significant effect on either neurobehavioral or cardiac outcome. PMID- 2105071 TI - Organ and tissue procurement in the acute care setting: principles and practice- Part 1. AB - The specialty of organ transplantation has grown tremendously during the past decade. With the advent of cyclosporine, artificial organs, and organ-assist devices, the possibility of suitable patients with end-stage organ disease becoming successful transplant recipients has increased dramatically. Consequently, the need for donor organs has risen. The greatest source of potential organ-tissue donors exists in the acute care setting (ie, emergency departments and intensive care units). To meet the need for this increasing demand, emergency physicians must become familiar with the techniques of procurement. Part 1 defines the problem of procurement and presents financial, historic, organizational, legal, and psychosocial aspects of organ-tissue procurement. A synopsis of brain death concludes the discussion. Part 2 (February 1990) presents aspects of the evaluation, selection, maintenance, and management of the organ-tissue donor. Disease transmission and controversial issues in organ tissue procurement also are discussed. PMID- 2105072 TI - Is pyrazinamide bactericidal against Mycobacterium tuberculosis? AB - Bactericidal activity of pyrazinamide (PZA) was tested at pH 5.6 in 7H12 broth against drug-susceptible M. tuberculosis strains. The highest tested concentrations of PZA, 500 and 1,000 micrograms/ml, killed no more than 76% of the bacterial population. These concentrations are more than 32 times greater than the minimal inhibitory concentration (MIC) and the achievable in vivo concentrations. Despite high clinical efficacy of PZA and its so-called sterilizing activity in mouse experiments, this drug is much less bactericidal in vitro than any other known antituberculosis drug. PMID- 2105073 TI - A new enzyme immunoassay specific for blastomycosis. AB - A highly specific enzyme immunoassay (EIA) was developed for the serodiagnosis of blastomycosis. Among the earliest sera available from eight active cases of blastomycosis, seven were reactive by EIA, three by immunodiffusion, and three by complement fixation. The one seronegative case was associated with acquired immunodeficiency syndrome (AIDS). No cross-reaction was observed with sera from 12 patients with active histoplasmosis or from five patients with active coccidioidomycosis or from 23 healthy persons. In contrast, all patients' sera cross-reacted in conventional EIAs based on commercial immunodiffusion antigens. The blastomycosis-specific EIA seems to offer sensitivity without compromising specificity. Rheumatoid factors, which could cause false-positive reactions, were controlled for. PMID- 2105074 TI - Immunosuppressive therapy for factor VIII inhibitors. PMID- 2105075 TI - Oxygen, food, and air travel. PMID- 2105076 TI - Kinetic analysis of the separate phosphorylation events in the phosphorylase kinase reaction. AB - Glycogen phosphorylase, a dimer of identical subunits, is activated by phosphorylase kinase-catalyzed phosphorylation of one serine residue in each subunit. In this paper, the effect of the phosphorylation of one subunit on the phosphorylation of the other subunit was examined. The three forms of phosphorylase, phosphorylase b (nonphosphorylated), phosphorylase ab (one subunit phosphorylated), and phosphorylase a (both subunits phosphorylated), were separated by anion-exchange high-performance liquid chromatography (HPLC). Purified phosphorylase ab was found to be stable under the conditions of the phosphorylase kinase assay. Initial rate kinetics showed that phosphorylase kinase had a lower KM for phosphorylase ab (3.9 +/- 0.24 microM) than for phosphorylase b (14.9 +/- 2.6 microM). Using the HPLC separation as a simultaneous assay for the three forms of phosphorylase during the phosphorylase kinase reaction, it was found that the pseudo-first-order rate constant for the second phosphorylation step (k2) was 3.7 times greater than that for the first step (k1). The activator AMP reduced the ratio k2/k1 from 3.7 without AMP to 1.4. When the monomeric gamma delta complex of phosphorylase kinase subunits was used as the enzyme, the ratio k2/k1 was 2.1, compared to 3.7 with the multimeric holophosphorylase kinase. One explanation for these data is that phosphorylation of one subunit of phosphorylase b causes conformational changes that make the other subunit a better substrate for the kinase. In this context, the effect of AMP is to reduce the conformational differences between phosphorylases b and ab, and the gamma delta complex is less sensitive to the conformational differences between the two forms of phosphorylase. PMID- 2105077 TI - ADP and glucose as possible synergistic partners in the stimulation of liver glycogen synthase activation. AB - Glucose administered either intravenously or orally causes liver glycogen synthase activation independent of a rise in circulating insulin. In vitro, physiological concentrations of glucose stimulate synthase phosphatase activity but only in the presence of a second effector which reduced the A0.5 for glucose. Caffeine and certain methylxanthines have been in vitro models for a putative natural effector. The present study demonstrates that, in vitro, ADP also reduced the A0.5 for glucose comparable to the effect of caffeine. The maximum stimulation by glucose in the presence of caffeine or ADP was comparable. The effect of ADP was specific among the major nucleoside diphosphates. However, the A0.5 for ADP was greater than the normal liver concentration which does not change in response to either glucose or insulin administration. The effect of ADP appeared distinct from that of the methylxanthines since it was observed that at near saturating concentrations of ADP and of glucose, stimulation was increased by addition of theophylline. Similarly, addition of adenosine, a natural cell constituent, caused increased stimulation. Subsequently, it was shown that adenosine reduced the A0.5 for ADP to a nearly physiological concentration. Thus, while ADP is not the inducible putative effector which has been predicted it may be part of an intracellular amplification system for glycogen synthase activation which increases the sensitivity to an induced effector. The present work suggests that the effective concentration of the natural ligand may be less than originally anticipated. This work also suggests that the putative effector could be structurally related to adenosine. Phosphorylase phosphatase activity known to be stimulated by ADP and glucose is further stimulated by the combination which may be acting in synergy. PMID- 2105078 TI - Distance measurements in cardiac troponin C. AB - Intramolecular distance measurements were made in cardiac troponin C (cTnC) by fluorescence energy transfer using Eu3+ or Tb3+ as energy donors and Nd3+ or an organic chromophore as acceptors. The laser-induced luminescence of bound Eu3+ is quenched in Eu1Nd1cTnC with a lifetime of 0.328 ms, compared with 0.43 ms for Eu2cTnC. The enhanced decay corresponds to an energy transfer efficiency of 0.25, or a distance of 1.1 nm between the two high affinity sites. We have also labeled cTnC with 4-dimethylaminophenylazophenyl-4'-maleimide (DAB-Mal) at the two cysteine residues (Cys-35 and Cys-84). Energy transfer measurements were carried out between Tb3+ bound to the high affinity sites and the labels attached to the domain containing the low affinity site. Upon uv irradiation at pH 6.7, Tb1cTnCDAB emits tyrosine-sensitized Tb3+ luminescence that decays bioexponentially with lifetimes of 1.29 and 0.76 ms. The shorter lifetime is ascribed to energy transfer from Tb3+ to the DAB labels, yielding an average distance of 3.4 nm between the donor and the acceptors. At pH 5.0, however, the luminescence decays exclusively with a single lifetime of 1.31 ms, suggesting that under these conditions all Tb3+ ions are more than 5.2 nm away from the label. Thus cTnC, like skeletal TnC, undergoes a pH-dependent conformational transition which converts an elongated structure at lower pH's to a rather compact conformation in a more physiological medium. PMID- 2105079 TI - Characterization of a ferredoxin:NADP+ oxidoreductase from a nonphotosynthetic plant tissue. AB - A flavoprotein with properties similar to those of ferredoxin:NADP+ oxidoreductases found in the leaves of higher plants has been purified to apparent homogeneity from bean sprouts, a nonphotosynthetic plant tissue. The absorbance and circular dichroism spectra of the bean sprout protein are similar to those of spinach leaf ferredoxin:NADP+ oxidoreductase and an antibody raised against the spinach enzyme recognized the bean sprout enzyme. The bean sprout enzyme catalyzed ferredoxin-dependent electron transfer from NADPH to equine cytochrome c at a high rate but, unlike the spinach enzyme, exhibited little NADPH to 2,6-dichlorophenol indophenol diaphorase activity. The bean sprout enzyme forms a 1:1 electrostatically stabilized complex with ferredoxins isolated from either bean sprouts or spinach leaves. PMID- 2105080 TI - Induction of the enzyme aldose reductase in a lens epithelial cell line from a transgenic mouse. AB - A lens epithelial cell line established from a transgenic mouse synthesizes high levels of the enzyme aldose reductase which converts sugars to polyols. This enzyme has been implicated in the formation of sugar cataracts in animals and with diabetic complications in man. The mouse aldose reductase has been characterized and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis has an apparent molecular mass of 38,000, similar to the enzyme in rat and man. The cellular enzyme is inhibited by two aldose reductase inhibitors: Sorbinil (IC50 = 1.8 X 10(-7) M) and Alcon 1576 (IC50 = 7.8 X 10(-8) M). The amount and the specific activity of the aldose reductase can be further increased in the cells by raising the osmolarity of the medium to 500 mOSM. Although the amount of aldose reductase is increased approximately sevenfold under these conditions, alpha-crystallin, one of the main lens specific proteins, remained at about the same concentration. No detectable increase in sorbitol was found within the cells, in contrast to published reports on renal cells in which this polyol increases under similar hyperosmotic conditions; however, in the lens cells there was a five-fold increase in the inositol content, suggesting that this polyol rather than sorbitol may be used to compensate for some of the changes in the osmolarity. The induction of the enzyme aldose reductase without the apparent accumulation of its product suggests a complex mechanism for osmoregulation in the lens cells. PMID- 2105081 TI - Expression of the yeast LEU4 gene is subject to four different modes of control. AB - A translational fusion of yeast LEU4 and Escherichia coli lacZ which contains 679 bp of the LEU4 5'-flanking region and the first two codons of LEU4 was used to study LEU4 expression. Eight recipient strains with different genetic backgrounds, transformed with a plasmid containing the fusion, were grown under a variety of conditions, and beta-galactosidase activity was measured. Evidence was obtained for at least four modes of expression of LEU4: general amino acid control, leucine-specific control, basal level expression, and branched-chain amino acid-mediated repression. Determination of steady-state levels of LEU4 mRNA suggested that LEU4 expression is regulated transcriptionally. PMID- 2105082 TI - Oxygenation of fluorinated tyrosines by mushroom tyrosinase releases fluoride ion. AB - The reactions of 2-fluoro- and 3-fluoro-L-tyrosine with mushroom tyrosinase have been investigated. Both fluorinated tyrosines are good substrates for tyrosinase, with Vmax and Vmax/Km values similar to those for L-tyrosine. Oxygenation of 2 fluorotyrosine is regioselective, and only 6-fluorodopa was detected by HPLC in reaction mixtures. Oxygenation of both isomers of monofluorotyrosine results in fluoride ion production in the absence of ascorbic acid; however, 2 fluorotyrosine also produces fluoride in the presence of ascorbic acid. These results are consistent with previous studies demonstrating rapid intramolecular cyclization of nascent 6-fluorodopaquinone (M.E. Rice, B. Moghaddan, C.R. Creveling, and K.L. Kirk, 1987, Anal. Chem. 59, 1534-1538), which is competitive with reduction by ascorbate, resulting in elimination of the aromatic fluorine as fluoride ion. PMID- 2105083 TI - Formation of cyclic imide-like structures upon the treatment of calmodulin and a calmodulin peptide with heat. AB - Protein cyclic imide is the putative intermediate in the formation of sites of carboxyl-methylation in eukaryotic proteins. Conditions known to induce the formation of a cyclic imide in model peptides have been applied to a protein, calmodulin. Heating of calmodulin in the dry state at 100 degrees C for 24 h after lyophilization from a pH 2.0 or pH 6.0 solution produces derivatives with altered chromatographic properties in anion-exchange HPLC. At pH 6.0, complete activity of calmodulin was retained. Analysis with Fourier transform infrared (FTIR)-photoacoustic spectroscopy demonstrated the presence of a new structure in the calmodulin molecule consistent with modification of carboxylic acid groups. The conversion of calmodulin is dependent upon the absence of Ca2+ (the presence of 1 mM ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid). A peptide analogous to the calcium binding regions of calmodulin, Asp-Lys-Asp-Gly Asn-Gly-Thr-Ile-Thr-Thr-Lys-Glu, is also converted, upon heating, to chromatographically different forms in reversed-phase chromatography. This process is also dependent upon the absence of calcium. Sequence analysis of the peptide derivatives reveals a second amino terminus, implicating peptide bond hydrolysis in the product. A dipeptide, Asp-Gly, known to form a cyclic imide structure under similar conditions is also hydrolyzed during sequence analysis consistent with cleavage occurring at the position of the cyclic imide structure. Asp3 is suggested to be the site of cyclic imide formation in the calmodulin peptide. The presence of a cyclic imide structure is also confirmed by the application of FTIR-photoacoustic spectroscopy. These data suggest that cyclic imide formation in calmodulin has been induced, possibly at one, or more, of the calcium binding loops of the protein. These modification reactions may provide a basis for future investigations of cyclic imide formation in proteins. PMID- 2105084 TI - [Enhancement of antitumor activity of mitomycin C against human breast carcinoma xenografts by pretreatment with KM 2210]. AB - Three human breast carcinoma xenografts, MCF-7, R-27 and T-61 serially transplanted into nude mice were treated with mitomycin C (MMC) alone, KM2210 (estra-1, 3, 5(10)-triene-3, 17 beta-diol, 3 benzoate 17-[4-(4-bis(2 chloroethyl)amino)phenyl)-1-oxobutoxy)acetate) alone and KM2210 followed by MMC. One hundred or 300 mg of KM2210 per kg were administered orally daily from Day 1 to 4 and MMC at the dose of 3 mg/kg was given ip on Day 5. The antitumor activity of MMC on these xenografts was enhanced by pretreatment with KM2210, suggesting a new combination chemo- and endocrine therapy of hormone-dependent human breast carcinomas. PMID- 2105085 TI - [A case report of advanced gastric cancer remarkably responding to mitomycin C, aclacinomycin A, SF-SP and lentinan combination therapy]. AB - A 63-year-old female diagnosed as inoperable gastric cancer was treated with combination immunochemotherapy of Mitomycin C, Aclacinomycin A, SF-SP and Lentinan. In this case, the tumor directly invaded the pancreas and the peritoneal dissemination, metastasis to the para-aortic lymph nodes and Virchow's metastasis were identified. As the result of this therapy, the primary tumor was remarkably reduced in size. The subjective symptoms and the metastasis of the para-aortic lymph nodes and Virchow's metastasis disappeared. The side effect was only mild thrombocytopenia. PMID- 2105086 TI - Immunosuppressive therapy of pemphigus vulgaris complicated by Nocardia pneumonia. Gold as an alternate therapy. PMID- 2105087 TI - Infusion of nifedipine after coronary artery bypass grafting decreases the incidence of early postoperative myocardial ischemia. AB - We performed a randomized study on patients undergoing elective coronary bypass grafting to examine whether postoperative infusion of nifedipine (n = 25) could reduce the incidence of isolated transient myocardial ischemia, myocardial infarction, or both. The control group (n = 25) received nitroglycerin. Hemodynamic and Holter monitoring and serial assessment of enzymatic and electrocardiographic changes were performed for all patients. Both groups showed comparable preoperative and operative data. The incidence of myocardial infarction was significantly lower in the nifedipine group (n = 1) as compared with the control group (n = 4), whereas the number of patients with isolated transient myocardial ischemia was similar in both groups (nifedipine, 3; control, 4). At the time of peak activity, levels of creatine kinase (350 +/- 129 versus 511 +/- 287 IU/mL), creatine kinase-MB (8.4 +/- 5.4 versus 17.1 +/- 11.0 IU/mL), and glutamate-oxaloacetate-transaminase (30.4 +/- 4.4 versus 41.0 +/- 7.9 IU/mL) were markedly lower in the nifedipine group (p less than 0.05). We conclude that infusion of nifedipine after elective coronary artery bypass grafting effectively decreases the incidence of myocardial infarction and the extent of myocardial necrosis during the early postoperative period. PMID- 2105088 TI - Carbaryl poisoning and edrophonium: electrophysiologic changes. AB - A case of poisoning with the insecticide carbaryl, a cholinesterase inhibitor, was studied using repetitive stimulation and edrophonium administration. Without edrophonium, repetitive stimulation studies were normal. After 5mg of edrophonium was administered intravenously, a 40% decrement was recorded using 3Hz stimulation and an 80% decrement was seen with 30Hz stimulation. It is concluded that edrophonium is useful in testing for poisoning with cholinesterase inhibitors when other electrophysiologic studies are normal. These changes are most likely due to a recently described fast desensitization of the acetylcholine (ACh) receptor induced by high ACh concentrations. PMID- 2105089 TI - Multiple orbital neurofibromas unassociated with von Recklinghausen's disease. AB - A 58-year-old man with a 10-year history of right periorbital pain treated with multiple analgesics presented with slowly progressive exophthalmos of the right eye. Orbital imaging studies disclosed three separate well-defined tumors, located in the temporal fossa, the intraconal space, and within the floor of the orbit. All three tumors were removed intact and proved on histopathologic evaluation to be localized neurofibromas. The patient had complete relief of the chronic pain following removal of the tumors. We emphasize that the unusual occurrence of multiple circumscribed orbital tumors should suggest the diagnosis of neurofibroma even in the absence of von Recklinghausen's neurofibromatosis. PMID- 2105090 TI - Interleukin-1 stimulates prostacyclin production by cultured human endothelial cells by increasing arachidonic acid mobilization and conversion. AB - Interleukin-1 (IL-1) induced slow, lasting activation of human endothelial cells (EC) to release prostacyclin (PGI2). This was accompanied by endogenous 3H arachidonic acid (3H-AA) release and by a time-dependent increase in the cells' ability to convert exogenous AA. The continuous presence of IL-1 was not required, but about a 1-hour stimulation with the cytokine was sufficient to trigger the cells to synthesize PGI2 for several hours. The spectrum of 3H-AA conversion shows that, in addition to 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha also was raised after IL-1. The recovery of PGI2 synthesis after aspirin was faster in IL-1-treated EC than in control cells. These data define some of the characteristics of IL-1 stimulation of PGI2 and suggest that this process is mediated both by endogenous AA mobilization and by an increase in cyclooxygenase activity. PMID- 2105091 TI - Use of synthetic peptide analogues to localize lecithin:cholesterol acyltransferase activating domain in apolipoprotein A-I. AB - The major protein of high density lipoprotein (HDL), apolipoprotein (apo) A-I, is the major activator of the plasma enzyme lecithin:cholesterol acyltransferase (LCAT). A consensus amino acid sequence has been defined for the eight, 22 residue long, tandem amphipathic helical repeats located in the carboxy-terminal region of apo A-I. A series of 22 and 44mer synthetic peptide analogues of the consensus domain, differing only in their 13th amino acid residue, were prepared and tested for LCAT activation. One of the peptides was found to equal apo A-I in LCAT activation. This is the first time a peptide activator for LCAT that rivals the activity of apo A-I in the vesicular and discoidal egg phosphatidylcholine assay systems has been synthesized. Based on these results, we propose that the major LCAT-activating domain of apo A-I resides in the 22mer tandem repeats, each containing Glu at the 13th residue and located between residues 66 and 121 in the native apolipoprotein. PMID- 2105092 TI - Diets rich in n-9, n-6 and n-3 fatty acids differentially affect the generation of inositol phosphates and of thromboxane by stimulated platelets, in the rabbit. AB - We have studied the effects of semi-synthetic diets rich in either n-9 (olive oil, OO) or n-6 (corn oil, CO), or n-3 (fish oil, FO, as MaxEPA) fatty acids on the levels of major PUFA in platelet lipids, on the generation of inositol phosphates by [3H]inositol labelled platelets after stimulation with thrombin and of thromboxane B2 (TxB2) by platelet rich plasma (PRP) after stimulation with collagen. The predicted elevations of oleic (OA), linoleic (LA) and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were observed in platelet lipids of each animal group, but in the MaxEPA fed group accumulation of EPA was associated with depletion of linoleic acid (LA) rather than of arachidonic acid (AA). Basal levels of inositol-tris-phosphate (IP3) in platelets were lowest in the OO group and highest in the CO group, whereas the increment after thrombin stimulation (1 unit/ml NIH) was maximal in the OO group and minimal in the FO group. Instead, when generation of TxB2 by stimulated platelets was evaluated, no appreciable difference among the various groups could be detected, in accordance with the limited modifications of platelet AA content induced by the diets. The overall data indicate that dietary fatty acids modulate the pathway of inositol phosphate generation in rabbit platelets, independently of modifications of TxB2 production. PMID- 2105093 TI - Effects of acute valproate administration on carnitine metabolism in mouse serum and tissues. AB - Carnitine concentrations in serum, liver, kidney, muscle and heart were determined 30 min, 2 hr and 4 hr after administration of single 50 mg/kg doses of valproic acid (VPA) or octanoic acid (OTA) of fasting mice. Half an hour post administration (p.a.) of VPA, free carnitine concentrations were smaller than in controls in serum, liver, kidney and heart. Four hr p.a., the effects of VPA had disappeared from all the carnitine sources, which now had concentrations that were not significantly different from those of controls. The effects of OTA are different from, and sometimes the opposite of, those of VPA, showing that the effects of VPA are specific to it. Hyperammonemia, on the other hand, was greatest 4 hr p.a. of VPA. These findings show that the effect of VPA on carnitine metabolism is immediate but transient, and accordingly suggest that the carnitine deficiency observed in patients under prolonged treatment with VPA containing anticonvulsants must be due to a more complex mechanism than direct interaction between carnitine and VPA. PMID- 2105095 TI - Effect of adenine nucleotides on cyclooxygenase and lipoxygenase enzyme products of arachidonic acid in human platelets. AB - Nucleotides are known to enhance cyclooxygenase product formation in several tissues and, in addition, are believed to function as cofactors for mammalian 5 lipoxygenases. Since nucleotides are released by stimulated platelets and by damaged tissue, we examined the hypothesis that nucleotides can affect the metabolism of arachidonic acid (AA) in washed human platelets. The various nucleotides were given 15 sec prior to the addition of 3 microM arachidonic acid and 1 muCi [3H]AA. We found that the phosphorylated adenine derivatives (ATP, ADP, and AMP) increased the formation of 12-hydroxyeicosatetraenoic acid (12 HETE) by 2-fold without altering the formation of cyclooxygenase products. Adenosine was without effect on 12-HETE formation. ATP also stimulated 12-HETE formation in lysed platelets. This suggests that the 12-lipoxygenase enzyme of platelets can be regulated by adenine nucleotides. We next determined the portion of the nucleotide molecule responsible for the enhanced 12-lipoxygenase activity of platelets. Alteration of the nucleotide base led to a decrease in stimulation, with GTP less active than ATP, and UTP even less active than GTP. Studies with adenine nucleotides showed that the length of the phosphate chain was not important. We also found that the stable methylene isosters of ATP (alpha, beta methylene ATP and beta, gamma-methylene ATP) increased 12-HETE formation, suggesting that the conformation and hydrolysis of the phosphate chain are not responsible for the stimulatory activity. Cyclic 3',5'AMP and 3'AMP were inactive, implying the necessity for a free phosphate at the 5' position for nucleotide stimulation of 12-HETE synthesis. In conclusion, platelet 12 lipoxygenase was stimulated by ATP, as is true for several mammalian 5 lipoxygenases. However, cyclooxygenase product formation by platelets was not altered by nucleotide addition. These studies suggest that following in vivo injury or platelet aggregation, when local concentrations of nucleotides are high, platelet lipoxygenase activity may be stimulated. PMID- 2105096 TI - The influence of dexamethasone on growth hormone (GH). Response to GH-releasing hormone in normal men. AB - There is evidence that glucocorticoids may have a bimodal effect on growth hormone release in vitro and in vivo. To explore the influence of a single low dose administration of dexamethasone on the hypothalamic-pituitary-somatotropic system, 11 male healthy subjects received 50 micrograms synthetic human GHRH-44 amide as an i.v. bolus dose with and without pretreatment with orally administered 1 mg dexamethasone 9 hours prior to GHRH stimulation. Dexamethasone preparation did affect neither baseline levels of GH and IGF-I nor GHRH induced GH secretory patterns assessed by delta max and by the net area under the response curves. These results add to previous reports that corticosteroids may have different effects on GH secretory dynamics dependent on dose and duration of application. PMID- 2105094 TI - Mechanisms of anti-carcinogenesis by indole-3-carbinol. Studies of enzyme induction, electrophile-scavenging, and inhibition of aflatoxin B1 activation. AB - The induction of oxidation and conjugation enzymes, the scavenging of carcinogen electrophiles, and the inhibition of aflatoxin B1 (AFB1) activation were examined as possible mechanisms of anti-carcinogenesis by indole-3-carbinol (I3C). Liver microsomal 7-ethoxycoumarin O-deethylase and 7-ethoxyresorufin O-deethylase activities were not induced significantly in rainbow trout fed diets containing 500-2000 ppm I3C for 8 days compared to trout fed the control diet. Furthermore, no detectable changes in the specific contents of cytochrome P-450 isozymes LM2 and LM4b, as measured by Western-blotting and immunoquantitation, were found in liver microsomes following dietary I3C administration. Dietary I3C had no significant effect on liver microsomal uridine diphosphate-glucuronyl-transferase activity, measured using the substrates 1-naphthol and testosterone, or on cytosolic glutathione S-transferase activity, measured using the substrate styrene oxide. The ability of I3C or its acid reaction products (RXM; generated by the reaction of I3C with HCl) to act as scavengers for the direct alkylating agent AFB1-8,9-Cl2 was examined. Addition of I3C or RXM to in vitro incubations did not inhibit the covalent binding of AFB1-8,9-Cl2 to calf thymus DNA. Kinetic analyses of microsome-mediated binding of AFB1 to DNA in vitro indicated that RXM inhibited the metabolic activation of AFB1. RXM increased the apparent Km for the AFB1-DNA binding reaction without changing the associated Vmax; the apparent Km values at 0, 3.5, 35, and 350 microM RXM were 35, 38, 66, and 86 microM for trout liver microsomes. RXM also inhibited the activation of AFB1 by rat liver microsomes, but I3C was not an effective inhibitor against AFB1-DNA binding mediated by either rat or trout liver microsomes. The results of the present study indicate that inhibition of microsome-activated AFB1 binding to DNA by I3C products may be of significant importance in I3C inhibition of hepatocarcinogenesis in trout and other species. The inhibition of carcinogen activation by I3C is contrasted with the mechanism of anti-carcinogenesis by beta naphthoflavone, which involves induction of xenobiotic metabolizing enzymes. PMID- 2105097 TI - G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain. AB - We detected the existence of Gi (the inhibitory G-protein) or Go (a similar G protein of unknown function) in the striatum of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The level of Gi/Go was significantly decreased by 42% in the putamen of the left hemisphere in schizophrenics; caudate head and globus pallidus levels were unchanged. Decreased Gi or Go may underlie enhanced dopamine function in the schizophrenic brain. PMID- 2105098 TI - Retrospective study of lithium use for institutionalized mentally retarded individuals with behavior disorders. AB - Severely and profoundly mentally retarded institutionalized residents (N = 74) who received lithium carbonate for various behavior disorders were followed in a 10-year retrospective study. Their disorders had not been responsive to other medications or treatments. Behavioral data had been recorded regularly and coordinated with medication use. Subjects who demonstrated a sustained major reduction or elimination of behavioral symptoms were classified as lithium responders (n = 31). Characteristics that indicated greater likelihood of response included older age and presenting symptoms of psychosis, although all characteristics studied were seen in both the responder and nonresponder group. PMID- 2105099 TI - The effects of phenytoin and carbamazepine on serum concentrations of mono unsaturated metabolites of valproic acid. AB - Serum concentrations of valproic acid (VPA) and its mono-unsaturated metabolites, 2-propyl-2-pentenoic acid (2-en), 2-propyl-3-pentenoic acid (3-en) and 2-propyl-4 pentenoic acid (4-en), were measured in 36 epileptic patients. The subjects were divided into three subgroups, i.e., receiving VPA alone (n = 20: VPA group), VPA with phenytoin (n = 9: VPA + DPH group), and VPA with carbamazepine (n = 7: VPA + CBZ group). In the VPA group, the correlations between the serum concentration of VPA and those of the metabolites were significantly positive (r = 0.693, P less than 0.01 for 2-en; r = 0.584, P less than 0.01 for 3-en; and r = 0.868, P less than 0.001 for 4-en). The concentration/dose ratio of VPA was significantly lower, and the 4-en/VPA ratio was significantly higher in the VPA + CBZ group than in the VPA group (P less than 0.05). However, DPH had less effect on the concentration/dose ratio of VPA and the 4-en/VPA ratio than CBZ. This may be due partly to the relatively smaller therapeutic dose of DPH. These results suggest a correlation between the serum concentration of VPA and that of 4-en, and an increased metabolic conversion of VPA to 4-en by coadministration of CBZ. High serum concentrations of VPA and concomitant use of CBZ resulted in an elevation of the serum concentration of 4-en, which has been reported to be the most toxic metabolite of VPA. PMID- 2105100 TI - Excretion of diazepam and its metabolites in human milk during withdrawal from combination high dose diazepam and oxazepam. AB - The excretion of diazepam, N-desmethyldiazepam, temazepam and oxazepam in breast milk was studied during withdrawal of a 22-year-old patient from combined high dose diazepam and oxazepam therapy. Concentrations of these benzodiazepines in plasma from both the woman and her nursing infant (1 year old) were also documented. Diazepam, N-desmethyldiazepam, temazepam and oxazepam were found in the maternal plasma and milk with mean milk: plasma ratios of 0.2, 0.13, 0.14 and 0.10 respectively. It was calculated on a mg kg-1 basis that the infant received some 4.7% of the maternal dose. Diazepam could not be detected in the infant's plasma, but low levels of N-desmethyldiazepam (20 and 21 micrograms l-1), temazepam (7 micrograms l-1) and oxazepam (7.5 and 9.6 micrograms l-1) were present. The infant showed no overt physical or mental symptoms of benzodiazepine intoxication. PMID- 2105101 TI - Expression and characterization of the intestinal Na+/glucose cotransporter in COS-7 cells. AB - Cells derived from the simian kidney, COS-7 cells, were transfected with a eucaryotic expression vector (pEUK-C1) containing the clone for the rabbit intestinal Na+/glucose cotransporter. Expression was monitored after transfection with lipofectin by measuring the initial rate of alpha-methylglucopyranoside (MeGlc) uptake. Cells transfected with vector containing the cDNA for the Na+/glucose cotransporter expressed Na(+)-dependent MeGlc transport. Neither control cells nor cells transfected with vector lacking cloned cDNA expressed the cotransporter. Na(+)-dependent MeGlc uptake into transfected cells was saturable (Km 150 microM), phlorizin-sensitive (Ki 11 microM), and inhibited by sugar analogs (D-glucose greater than MeGlc greater than D-galactose greater than 3-O methyl-D-glucoside greater than D-allose much greater than L-glucose). Europium was able to mimic Na+ in driving MeGIC uptake. Finally, tunicamycin, an inhibitor of asparagine-linked glycosylation, inhibited the expression of Na(+)-dependent MeGlc transport 80%. We conclude that the rabbit intestinal Na+/glucose cotransporter expressed in COS-7 cell exhibits very similar kinetic properties to that in the native brush border and to that expressed in Xenopus oocytes. In addition, N-linked glycosylation appears to be important for functional expression of this membrane protein. PMID- 2105102 TI - Induction of fos and sis proto-oncogenes and genes of the extracellular matrix proteins during butyrate induced glioma differentiation. AB - Sodium butyrate has been shown to inhibit the growth and induce the differentiation of F-98 rat glioma cells. In agreement with the morphological changes, we have found that mRNAs for fibronectin and collagen in these cells could be reversibly induced by butyrate. While Ki-ras mRNA levels remained relatively unchanged, mRNAs for fos and sis increased significantly during the course of butyrate induced differentiation. c-fos induction can be detected 30 min after butyrate addition, a peak level (greater than 20 fold) was reached at 2 h, with a subsequent gradual decline. c-sis induction was detectable 24 h after butyrate exposure, at which time the cells have assumed morphological transition. Interestingly, the sis mRNA induction was not reversible upon butyrate withdrawal. The sis mRNA half-life increased from 40 min in the untreated cells to 100 min in the butyrate induced cells indicating that the increase in the stability of sis mRNA contributed, at least in part, to the elevated levels of sis expression. These findings demonstrate a coordinated induction of fibronectin and collagen genes in the butyrate-treated F-98 cells. In addition, fos and sis transcripts were differentially induced; a rapid and transient induction of fos followed by an irreversible induction of sis at a later stage of differentiation. PMID- 2105103 TI - Galactose inhibits lactase expression by mouse jejunal enterocytes. AB - Present work uses a combination of quantitative cytochemistry and measurements of cell migration rates to describe galactose effects on lactase expression by mouse enterocytes. Mice fed galactose were found to eat less, weigh less and drink more than mice maintained on a low-carbohydrate isocalorific diet. The enterocyte migration rate in these mice was also only one third of that determined in low carbohydrate-fed animals. The rate at which lactase activity increased in the brush border membrane of migrating enterocytes was 3-times greater in low carbohydrate- compared with galactose-fed mice. The time during which this increase persisted was, however, 3-times less in low-carbohydrate-fed animals. The maximum rate of sucrase-maltase appearance, measured as control in these experiments, remained unaffected by galactose feeding. Galactose effects on lactase expression might in part result from mice being unable to metabolise this substrate. Previously it has been stated that galactose increases lactase biosynthesis in rat intestine (Koldovsky, O., Bustamonte, S. and Yamada (1981) In Mechanisms of intestinal adaptation (Robinson, J.W.L., Dowling, R.H. and Ricken, E.O., eds.), pp. 153-156, MTP Press, Lancaster). This result is discussed in relation to the opposite finding reported in the present work for mouse jejunal enterocytes. The need to relate enzyme appearance to age and developmental state of enterocytes in this type of study is also emphasized. PMID- 2105104 TI - Stimulus-response coupling in FMLP-stimulated U937 monocytes: effect of differentiation on Gi2 expression. AB - The effect of differentiation on FMLP-stimulated InsP production and G-protein expression was investigated in U937 monocytes. FMLP (0.01-10 microM) stimulated [3H]InsP production in dimethyl sulphoxide-differentiated, but not in immature, U937 cells. Ionomycin (1 and 10 microM) stimulated [3H]InsP production equally well in both cell types. The FMLP response was blocked by pertussis toxin (100 ng/ml for 4 h) which catalysed [32P]ADP ribosylation of a 40 kDa 'Gi-like' G protein alpha subunit in these cells. This protein was also identified immunologically using anti-peptide antibodies that detect 'Gi-like' alpha subunits (SG2) or Gi2 alpha specifically (LE2). With LE2 a 5-fold increase in Gi2 alpha levels was seen following differentiation of the cells, suggesting that FMLP receptor expression is accompanied by an increase in the G-protein with which these receptors interact. PMID- 2105105 TI - Thyrotropin and prolactin response to thyrotropin-releasing hormone in depressed and nondepressed alcoholic men. AB - Thyrotropin-releasing hormone (TRH) stimulation tests were performed on 81 alcoholic men after at least 3 weeks of abstinence. Subjects were given 500 micrograms of TRH intravenously, and thyroid-stimulating hormone (TSH) and prolactin (PRL) were measured at baseline, and then 15 and 30 min later. Comparisons were made among alcoholics with (n = 27) and without (n = 54) a lifetime history of depression as determined by the Diagnostic Interview Schedule. Nine nondepressed, nonalcoholic subjects served as controls. Alcoholics with or without a depression history did not differ from each other or from control in TSH or PRL response area under the curve. Blunted TSH responses were present in 10 (12%) of the alcoholics and none of the controls when blunting was defined as a delta max TSH less than 5 microU/ml. When blunting was defined as a delta max TSH less than 7 microU/ml, 18 (22%) of the alcoholics and 1 (1%) of the controls were blunted. Conversely, 2 (2.5%) of the alcoholics had a delta max TSH greater than 32 microU/ml. All subjects were clinically euthyroid. Contrary to expectation, depressed subjects were slightly less likely to show blunted responses than nondepressed subjects. No relationship was found between neuroendocrine measurements and several measurements of alcoholism or depression. Some alcoholic subjects show a blunted TSH response to TRH injection, which may be a function primarily of the alcoholism itself. The precise mechanism remains unknown. PMID- 2105106 TI - Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent. AB - Hemophilia A (HA), a common inherited bleeding disorder in humans, is due to the deficiency or absence of the factor VIII (FVIII) activity. The cloning of the FVIII gene has made molecular probes available for the characterization of the basic defect in this disease. In this study we describe six different mutations in the FVIII gene detected by DNA analysis of 100 HA patients of Italian descent. In two of them, with a severe clinical picture, we identified two novel deletions, one in the middle of the FVIII gene from exons 7 to 22 and the other encompassing the entire factor VIII gene. Both of these patients produced antibodies to factor VIII. In a patient with mild HA we detected a duplication of exon 13, which is a rearrangement not yet described within the FVIII gene. A possible explanation for the mild phenotype in this patient is that the molecular defect results in the production of an unstable FVIII protein with residual 10% FVIII activity. Screening by Taq I restriction endonuclease detected three mutations that were further characterized by direct sequencing on amplified DNA: a C-T substitution at codon 1960, in exon 18, converting the codon for arginine to a non-sense codon; and a G-A substitution at codon 2228 and 2326, in exons 24 and 26 respectively, resulting in the substitution of glutamine for arginine. All three of these mutations have been previously described. The non-sense mutation and the codon 2228 G-A mutation was found in patients with severe HA, while the codon 2326 G-A mutation was associated with a quite severe condition. These results confirm that the molecular bases of HA are very heterogeneous and provide further evidence that recurrent mutations are not uncommon in this system. PMID- 2105107 TI - Differential regulation by cytokines of constitutive and stimulated secretion of von Willebrand factor from endothelial cells. AB - We examined the effect of cytokines on basal and agonist-stimulated release of von Willebrand factor (vWf) by human endothelial cells. Treatment of endothelial cells for up to 48 hours with human recombinant or purified interleukin 1 (IL-1) or human recombinant tumor necrosis factor-alpha (TNF-alpha) did not significantly affect constitutive secretion of vWf or intracellular levels of vWf, although basal prostacyclin (PGI2) production was markedly enhanced. In contrast, both IL-1 and TNF-alpha modulated vWf release in response to thrombin or phorbol ester. Pretreatment of endothelial cells for 2 hours with either cytokine enhanced by up to threefold the stimulatory effect of a subsequent 60 minute exposure to thrombin. Addition of cycloheximide (5 micrograms/mL) during the preincubation abolished this enhancement. Moreover, if the cytokine pretreatment time was extended to 24 hours, agonist-stimulated vWf release was significantly suppressed. Cytokine treatment for 2 or 24 hours had no detectable effect on levels of vWf messenger RNA. The effects of cytokines were not the result of contamination with bacterial lipopolysaccharide and were not attributable to endothelial cell injury. These results show that cytokines have little or no direct effect on vWf release from endothelial cells but can significantly modulate its acute release in response to other stimuli in a complex time- and dose-dependent manner. PMID- 2105108 TI - Induction of differentiation in blast cells and leukemia colony-forming cells from patients with acute myeloid leukemia. AB - The characteristic lesion in acute myeloid leukemia (AML) is the failure of myeloid cells to differentiate normally, leading to the accumulation of immature blast cells (BC) in the bone marrow. We determined whether BC and leukemia colony forming cells (L-CFC) from AML patients could differentiate in vitro after short term culture with interferon-gamma (IFN gamma), 1,25 dihydroxyvitamin D3 (D3), retinoic acid (RA), tumor necrosis factor-alpha (TNF alpha), and granulocyte monocyte colony-stimulating factor (GM-CSF). Expression of myeloid differentiation antigens CD15, CD14, CD33, and p124 was determined on the BC by immunofluorescence and on the L-CFC by monoclonal antibody (MoAb) and complement (C')-mediated cytotoxicity followed by cloning in methylcellulose. We found that 26 of 39 (67%) cases demonstrated changes in the expression of myeloid differentiation antigens on the BC, and 6 of 7 (86%) cases showed an altered L CFC myeloid antigen phenotype after short-term culture with differentiating agents. Alterations in myeloid antigen expression in the L-CFC population correlated with a reduction in L-CFC cloning potential. In the BC, alterations of myeloid differentiation antigens occurred in a manner consistent with those observed during normal myelopoiesis. For example, CD14 antigen expression (a late stage monocyte antigen) increased on BC from 12 of 39 (31%) cases, and p124 (an antigen expressed both by myeloid progenitor cells and by a subset of monocytes) increased on 15 of 39 (38%) cases. Changes in the expression of CD33 antigens (expressed normally by myeloid progenitor cells and by mature monocytes) on the BC were variable, with 7 of 29 cases (24%) showing a decrease and 7 of 29 cases (24%) showing an increase. When comparisons were made between pairs of differentiation agents that caused the altered expression of an antigen on either the BC or L-CFC of a patient, the majority of changes were in the same direction (either both "increased" or both "decreased"). This suggests that the direction of antigen change is characteristic of the leukemia cell subpopulation for each patient and not of the stimulatory agent. This study demonstrates that cells from more than two thirds of AML cases examined responded to various differentiation agents in vitro as measured by changes in the expression of myeloid cell associated surface antigens and by alterations in cloning potential of the L-CFC, a finding of potential clinical significance. PMID- 2105109 TI - Factor concentrates for treatment of hemophilia: clarification. PMID- 2105110 TI - Modulation of human monocyte functions by factor VIII-anti-factor VIII complexes present in an affinity-purified factor VIII product. PMID- 2105111 TI - Recombinant interferon-alpha, but not interferon-gamma is effective therapy for essential thrombocythemia. AB - Recombinant interferon-gamma with a starting dose of 0.5 mg 3x/week subcutaneously, was administered to 6 patients with essential thrombocythemia (median platelet count 1172 X 10(9)/l, range 602-1564). Four of the patients had received alkylating agents previously. Hematological remission, defined as a decrease in platelet counts to less than or equal to 350 X 10(9)/l, was observed in none of these patients. Subsequently 4 of these 6 patients, supplemented by 2 others were treated with interferon-alpha 2c at a dose of 5 X 10(6) U daily subcutaneously. Five patients showed hematological remission. In case of hematological remission the interferon-alpha doses was reduced to 5 X an thereafter to 3 X weekly 5 X 10(6) U. During an observation period ranging from 12-41 weeks platelet counts remained normal in all patients. Side-effects were mild and consisted of fever, myalgias, malaise and itching occurring mainly during the first month of treatment. No dose adaptation was required. The patients treated previously with interferon-gamma experienced the side effects from this drug less tolerably than those from the alpha-compound. These observations suggest that recombinant interferon-alpha may be an effective drug in treating essential thrombocythemia resulting in a sustained response. PMID- 2105112 TI - Colour Doppler flow mapping. PMID- 2105113 TI - Protective effect of breast feeding against infection. AB - OBJECTIVE: To assess the relations between breast feeding and infant illness in the first two years of life with particular reference to gastrointestinal disease. DESIGN: Prospective observational study of mothers and babies followed up for 24 months after birth. SETTING: Community setting in Dundee. PATIENTS: 750 pairs of mothers and infants, 76 of whom were excluded because the babies were preterm (less than 38 weeks), low birth weight (less than 2500 g), or treated in special care for more than 48 hours. Of the remaining cohort of 674, 618 were followed up for two years. INTERVENTIONS: Detailed observations of infant feeding and illness were made at two weeks, and one, two, three, four, five, six, nine, 12, 15, 18, 21, and 24 months by health visitors. MAIN OUTCOME MEASURE: The prevalence of gastrointestinal disease in infants during follow up. RESULTS: After confounding variables were corrected for babies who were breast fed for 13 weeks or more (227) had significantly less gastrointestinal illness than those who were bottle fed from birth (267) at ages 0-13 weeks (p less than 0.01; 95% confidence interval for reduction in incidence 6.6% to 16.8%), 14-26 weeks (p less than 0.01), 27-39 weeks (p less than 0.05), and 40-52 weeks (p less than 0.05). This reduction in illness was found whether or not supplements were introduced before 13 weeks, was maintained beyond the period of breast feeding itself, and was accompanied by a reduction in the rate of hospital admission. By contrast, babies who were breast fed for less than 13 weeks (180) had rates of gastrointestinal illness similar to those observed in bottle fed babies. Smaller reductions in the rates of respiratory illness were observed at ages 0-13 and 40 52 weeks (p less than 0.05) in babies who were breast fed for more than 13 weeks. There was no consistent protective effect of breast feeding against ear, eye, mouth, or skin infections, infantile colic, eczema, or nappy rash. CONCLUSION: Breast feeding during the first 13 weeks of life confers protection against gastrointestinal illness that persists beyond the period of breast feeding itself. PMID- 2105114 TI - Monitoring of blood glucose concentration in subjects with hypoglycaemic symptoms during everyday life. AB - OBJECTIVE: To study the persistence of hypoglycaemic symptoms, changes in blood glucose concentrations, and the relation between reported symptoms and measured blood glucose values in functional hypoglycaemia. DESIGN: Re-evaluation of symptoms in patients admitted consecutively with suspected hypoglycaemia followed by a case-control study. SETTING: The Steno Memorial Hospital in Gentofte, Denmark, which specialises in the diagnosis and treatment of and research on endocrine disorders, including hypoglycaemia. PATIENTS: 21 Subjects admitted consecutively with hypoglycaemic symptoms that were relieved by eating in whom insulinoma and other organic disorders presenting with hypoglycaemia had been ruled out. Twelve of these subjects with persistent symptoms entered the case control study, as did a matched control group. INTERVENTIONS: Four days of monitoring blood glucose concentrations at home, six daily samples being taken in fixed relation to meals by the finger prick method. Extra samples were taken when symptoms occurred. MAIN OUTCOME MEASURES: Blood glucose concentration, glycated haemoglobin concentration, and within subject variation in measured values. RESULTS: After one to three years of observation 19 of the 21 subjects still had symptoms. Six out of 12 subjects experienced hypoglycaemic symptoms during the controlled study. Blood glucose concentration ranged from 3.7 mmol/l to 7.5 mmol/l during these episodes. Changes in blood glucose concentration, mean blood glucose concentrations at each time point, within subject variation in the measured values, and glycated haemoglobin concentration were not significantly different in all patients compared with the control subjects and in patients with symptoms during the study compared with controls. CONCLUSION: Hypoglycaemic symptoms during everyday life in apparently healthy subjects are persistent but are not related to chemical hypoglycaemia. PMID- 2105115 TI - Single dose cefotaxime plus metronidazole versus three dose cefuroxime plus metronidazole as prophylaxis against wound infection in colorectal surgery: multicentre prospective randomised study. AB - OBJECTIVE: To establish whether a single preoperative dose of cefotaxime plus metronidazole was as effective as a standard three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery. DESIGN: Prospective randomised allocation to one of two prophylactic antibiotic regimens in a parallel group trial. Group sequential analyses of each 250 patients were performed. SETTING: 14 District general and teaching hospitals. PATIENTS: 1018 Adults having colorectal operations were randomised, of whom 943 were evaluated. Demographic features, conditions requiring surgery, and operative procedures were similar in the two groups. Most patients had surgery for carcinoma of the colon or rectum. INTERVENTIONS: Group 1 received cefotaxime 1 g intravenously plus metronidazole 500 mg intravenously preoperatively. Group 2 received cefuroxime 1.5 g intravenously plus metronidazole 500 mg intravenously preoperatively, followed by cefuroxime 750 mg intravenously plus metronidazole 500 mg intravenously eight hours and 16 hours postoperatively. MAIN OUTCOME MEASURES: Development of surgical wound infection (as evidenced by the presence of pus), death, or discharge from hospital. RESULTS: Wound condition was scored on a five point scale on alternate days until discharge or for up to 20 days postoperatively. Wound infection rates were: group 1, 32/453 (7.1%; 95% confidence interval 4.7% to 9.4%); group 2, 33/454 (7.3%; 95% confidence interval 4.9% to 9.6%). Death rates (group 1: 26/470 (5.5%); group 2: 31/471 (6.6%], the incidence of postoperative complications, the median duration of hospital stay (12 days), and antibiotic tolerance were all similar in the two groups. Pooled data from groups 1 and 2 showed that wound infections were more frequent when minor faecal contamination had occurred at operation and when the duration of operation exceeded 90 minutes (greater than 90 min 11.2% of cases; less than 90 min 4.8%) and were associated with an extended hospital stay. CONCLUSIONS: A single preoperative dose of cefotaxime plus metronidazole is an efficacious as a three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery and has practical advantages in eliminating the need for postoperative antibiotics. PMID- 2105116 TI - Prophylactic antibiotics and caesarean section. PMID- 2105117 TI - Stimulating reporting of adverse drug reactions by using a fee. PMID- 2105118 TI - Women's knowledge of their HIV antibody state: its effect on their decision whether to continue the pregnancy. PMID- 2105119 TI - Lingual cellulitis causing upper airways obstruction in neutropenic patients. PMID- 2105120 TI - Overprescription of cholera vaccine to travellers by general practitioners. AB - A questionnaire describing five hypothetical patients intending to travel to different countries was sent to 113 general practitioners, who were asked to state which patients they would recommend cholera vaccination to. The response rate was 80%. The general practitioners' recommendations were compared with those of the Liverpool School of Tropical Medicine. Sixty three of 86 respondents recommended cholera vaccination when it would probably have been unnecessary. A review of common sources of information on cholera vaccination showed that general practitioners are given confusing or inappropriate advice. General practitioners should be educated about when cholera vaccination is necessary; alternatively, the vaccine should be available only through special centres. PMID- 2105121 TI - No experience necessary? PMID- 2105123 TI - Write a classic paper. PMID- 2105122 TI - Hospital formularies: need for continuous intervention. AB - The effects of introducing a hospital formulary alone and with active intervention were compared prospectively with regard to drug costs and the quality of prescribing. Intervention comprised feedback on prescribing habits, peer comparison, and information on drugs. Aspects of prescribing that were not subjected to intervention did not alter. In the year in which intervention occurred generic prescribing rose by 50%; inappropriate prescribing and overall use of third generation cephalosporins fell; and compliance with the recommended list of drugs was good. Overall, drug costs remained static, compared with a projected increase of 0.25 m pounds; in a comparative control hospital drug costs rose by 18%. During the next year, when no form of intervention took place, previous gains were eroded and drug costs rose. Continuous intervention, review, and feedback are required if a formulary is to continue to achieve its objectives. PMID- 2105124 TI - Housing and health: health and homelessness. PMID- 2105125 TI - ABC of transfusion. Human albumin solutions. PMID- 2105126 TI - Guidelines for writing papers. PMID- 2105127 TI - Shortage of therapists. PMID- 2105128 TI - Cardiopulmonary resuscitation and the MRCGP examination. PMID- 2105129 TI - Oestrogen deficiency and estradiol implants. PMID- 2105130 TI - Housing and health. PMID- 2105131 TI - Seizure related to erythropoietin treatment in patients undergoing dialysis. PMID- 2105132 TI - The cyclotron saga continues. PMID- 2105133 TI - Complementary medicine. PMID- 2105134 TI - Ethnic differences in consultation rates. PMID- 2105135 TI - Herbal remedies. PMID- 2105136 TI - Personal views. PMID- 2105137 TI - Treatment protocols, specialist centers, and end results. PMID- 2105138 TI - Hazards of blood splashes. PMID- 2105139 TI - Laying down the law on AIDS. PMID- 2105140 TI - Audit in general practice. PMID- 2105141 TI - Monitoring the prevalence of HIV. PMID- 2105142 TI - Fulminant hepatic failure following bone marrow transplantation for hepatitis associated aplastic anemia. AB - A case of aplastic anemia associated with non-A, non-B hepatitis was initially successfully treated by bone marrow transplantation. The patient subsequently developed fulminant hepatic failure. Fulminant hepatic failure is rare in bone marrow transplantation and only occurs in association with aplastic anemia associated with viral hepatitis. This case helps to highlight the relationships between the immune system, hepatitis, and bone marrow failure. PMID- 2105143 TI - Psychosocial predictors of psychopathology in epilepsy. AB - The 30-item version of the GHQ was administered to 102 adults with epilepsy, and four sets of variables (neurological, psychosocial, medication, demographic) were used to predict psychiatric distress. Psychopathology was found to be associated with increased perceived stigma, elevated number of stressful life events during the past year, poor adjustment to epilepsy, financial stress, vocational problems, external locus of control, and an earlier onset of epilepsy. Multiple regression procedures reduced this list to three independent predictors of psychopathology: an increased number of stressful life events in the past year, poor adjustment to epilepsy, and financial stress. PMID- 2105144 TI - [Increase of circulating levels of thymulin in hyperprolactinemia and acromegaly]. AB - The production of thymulin by the thymic epithelium is under complex control involving the endocrine system. Experimental models have suggested that prolactin (PRL) and growth hormone (GH) participate in this regulation but this has not been documented in humans. Using a bioassay we measured circulating thymulin levels in patients with hyperprolactinemia (n = 21), acromegaly (n = 15), or both (n = 6). Thymulin was elevated in these three groups of patients compared with normal subjects or with patients with pituitary disease but no excess in PRL or GH. Contrasting with observations in control groups, thymulin did not decrease as a function of age in patients. No correlation between thymulin and PRL or GH levels was observed while thymulin and insulin-like growth factor 1 levels were correlated. A new radioimmunoassay used in some patients for thymulin determination yielded similar results. Overall these data demonstrate that PRL and GH are involved in the hormonal control of thymulin production by the thymic epithelium in the human. PMID- 2105145 TI - [Demonstration of 3 functional domains responsible for a kinase activity in VirA, a transmembrane sensory protein encoded by the Ti plasmid of Agrobacterium tumefaciens]. AB - High-level expression of chimeric virA genes were obtained by replacing the first codons of virA with the first codons of trpE. The fusion proteins encoded by these constructs were partially purified and one of them exhibited autokinase activity. Therefore, protein phosphorylation may be an important feature of VirA function. This allowed us to define the existence of three functional domains inside VirA. PMID- 2105146 TI - [State of equilibrium among agonistic behaviour patterns in a group of Japanese macaques (Macaca fuscata)]. AB - The degree of aggressive intensity, the degree of contest asymmetry and the development of conciliatory patterns were studied in a captive group of Japanese macaques (Macaca fuscata). The state of equilibrium among these components varied according to relatedness of interacting individuals, the observed variations being analogous to those found in interspecific comparisons. It is concluded that the relations linking these components result from epigenetic processes which govern the emergence of a social organization. PMID- 2105147 TI - Nondestructive measurement of bone mineral in femurs from ovariectomized rats. AB - One hundred ninety-eight rats were ovariectomized (OX) or sham-ovariectomized (shOX) at 100 days of age. Groups were killed at 35, 70, 100, 125, 180, 270, 360, and 540 days postsurgery. Bone mineral content (BMC) of the right femur was assayed on a dual photon absorptiometer (DPA) optimized for human spine and whole body measurements. Three regions were studied: the distal measuring 0.8 cm, the proximal measuring 0.88 cm, and the diaphysis, the remainder. The DPA technique accurately showed the ash content (r = 0.96), with a precision error of 3-5%. Whole femoral BMC was 4.3-11.1% lower in OX than shOX rats, with significant differences from 35-180 days. By 35 days, distal femoral BMC declined 6% in OX rats and rose 12% in shOX rats. Distal femoral BMC was 11.3-17.5% lower in OX than shOX rats, with significant differences at all times except 540 days. Femoral diaphyseal BMC of OX and shOX rats did not differ at any time. The relative distal femoral osteopenia which appeared by 35 days in OX rats did not worsen during the next 17 months. A DPA suited for human BMC studies is also accurate for BMC determination in bones with 250-500 mg of mineral. It is less precise for this purpose than dedicated instruments using single photon absorptiometry. However, enough precision exists to monitor the development of relative osteopenia in OX rats. Osteopenia in OX rats is confined to a region containing appreciable cancellous bone. Its self-limiting nature suggests the existence of an estrogen-dependent quantum of cancellous bone in female rats. The adult rat model is accurate for cancellous bone of the adult human, but inaccurate for cortical bone. PMID- 2105148 TI - Elongation of fetal chick long bone in vitro is formed by a mitogenic activity preparation from porcine bone. AB - Elongation of fetal chick long bone rudiments is formed by a mitogenic activity from porcine bone in vitro. Fractions of mitogenic activity from a heat- and acid treated extract and from sequential chromatography on hydroxyapatite and from gel filtration in 4 M guanidine-HCl increase diaphyseal elongation of metatarsals. The bone elongation-forming activity is associated with the mitogenic activity estimated by the incorporation of [3H]-methyl thymidine into the DNA of cells from embryonic chick periosteum. Histological examination of the mitogen-treated embryonic chick long bone shows that the partially purified fractions with a preferential effect on osteogenic cells increase diaphyseal elongation via cartilage cell proliferation. PMID- 2105149 TI - Membrane-associated crystallization of calcium oxalate in vitro. AB - Incubation of proximal tubular brush border membrane in a metastable calcium oxalate solution of low supersaturation resulted in the equimolar depletion of calcium and oxalate and the formation of monoclinic calcium oxalate crystals. We propose that membrane fragments from sloughed epithelial cells of the nephron can similarly induce crystallization in urine that is metastable for calcium oxalate. PMID- 2105150 TI - Absorption of intranasal salmon calcitonin in normal subjects and hypogonadic men. AB - The absorption kinetics of intranasal salmon calcitonin were assessed in 4 normal subjects and 9 patients with Klinefelter's syndrome. After administration, absorption occurred within 5 minutes. There was a highly significant correlation between the amount administered and the amount absorbed (r = -0.83, P less than 0.0005). PMID- 2105151 TI - Hip fractures in young patients: is this early osteoporosis? AB - Hip fracture in patients under age 50 is rare, and is often not attributable solely to the energy of injury. Our aim was to determine if trabecular bone mineral density (BMD) is abnormal in young patients with hip fractures. We reviewed all hip fractures treated at our institution between 1979 and 1986 and contacted 20 patients under the age of 50 at the time of injury, all of whom wished to be studied. The mean age at the time of injury was 39 (range 24-47). Subjects were questioned for osteoporosis risk factors, classified by level of energy producing their injury, and then underwent quantitative computed tomography (QCT) bone densitometry of trabecular bone in the lumbar spine. Bone mineral density by QCT was below the mean for age in 90% of the patients, and was greater than 1 SD below the mean in 75%. Mean percentage BMD decrease from age matched controls was 34% (P less than 0.005) in women and 19% (P less than 0.005) in men. There was an inverse correlation in the degree of BMD decrease and the energy level of injury. There was a direct correlation of the severity of BMD decrease and the cumulative number of osteoporosis risk factors. This investigation has found that 1-7 years following hip fracture, otherwise presumedly healthy young patients demonstrate a statistically significant decrease in spinal BMD from age/sex-matched controls. These data do not determine if osteopenia is the cause or the result of injury, nor do we wish to infer that measurement of bone density at one site can predict future fractures at other sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105152 TI - Intestinal calcium absorption during hyperinsulinemic euglycemic glucose clamp in healthy humans. AB - The influence of postprandial-like plasma insulin levels on intestinal calcium absorption (CaA) was studied in 9 healthy men. On separate occasions, they received either an i.v. infusion of 40 mU/m2 minute synthetic human insulin as well as a variable glucose infusion in order to clamp the plasma glucose at the baseline level (= glucose clamp), or insulin- and glucose-free vehicle infusions (= vehicle). During these infusions, an oral load containing 326 mg Ca in the form of Ca chloride was administered and CaA was determined thereafter with a 47Ca/85Sr double tracer method. During glucose clamp, mean plasma insulin was 172 +/- (1 SEM) 10 as compared to 6 +/- 1 microU/ml during vehicle infusions. During the clamp, 3-hour cumulative CaA rose significantly by 14% as compared to vehicle (39.2 +/- 2.5 vs. 34.4 +/- 2%, P less than 0.02). AT the same time, serum potassium and phosphorus dropped significantly, whereas serum parathyroid hormone (PTH) and 1,25(OH)2D levels were unchanged as compared to vehicle. The urinary excretions of potassium, sodium, and inorganic phosphorus, as well as the urinary specific activity of 47Ca, dropped significantly during glucose clamp, whereas the urinary excretion of cAMP was unchanged as compared to vehicle. The results suggest that, under the conditions of euglycemic hyperinsulinemic clamp, insulin stimulates CaA of healthy humans in a PTH- and 1,25(OH)2D-independent manner. Insulin may thus possibly be regarded as a factor participating in the regulation of CaA in humans. PMID- 2105153 TI - Long-term physical exercise retards trabecular bone loss in lumbar vertebrae of aging female mice. AB - The present study examined the effect of long-term, moderate physical exercise on trabecular bone volume (TBV), calcium content, 3H-proline uptake, and the activities of alkaline and acid phosphatases in lumbar vertebrae of aging and senescent mice. It became apparent that if physical activity starts at an early stage of life, i.e., prior to middle age and is extended until old age, it exerts beneficial effects on trabecular bone mass and mineralization. Such a positive effect is not obtained if the training program is initiated after middle age. The training-induced reduction in bone loss was accompanied by a significant decrease in acid phosphatase activity whereas no changes took place with regard to the activity of alkaline phosphatase. Long-term physical exercise also enhanced the uptake of 3H-proline by lining cells along the bone trabecules. In spite of its moderate nature, the endured training program served as a stress factor for the involved animals, a fact that was manifested by an increase in the serum levels of corticosterone. Thus, it seems that whereas young animals respond favorably to such a stimulatory stress, older animals lose this ability of adaptation. PMID- 2105154 TI - 224Ra-induced osteopenia in male CBA mice. AB - Six groups of young adult, male mice were injected with six dose levels of the bone-seeking, alpha-emitting radionuclide 224Ra (half-life 3.6 days); a seventh group was injected with saline alone. The administered doses were relatively low, ranging from 2 to 64 kBq per animal. The mice were maintained under standard laboratory conditions until they either died or became moribund, when they were killed. The mean ages at death of the experimental groups were not significantly different from the normal control group. Individual bones--the mandible, parietal, nasal, and bulla--were isolated and standard linear measurements and dry weights were obtained. In all measurements considered, the highest two administered amounts (32 and 64 kBq) caused a significant reduction relative to controls. Low power microscopy of the mandible revealed osteonecrosis in the high dose groups. This is similar to the condition of "radium jaw" which has been described as a late effect of either accidental ingestion or therapeutic administration of 226Ra (half-life 1,620 years) in man; the other bones did not show obvious osteonecrosis. This work emphasizes the long-term osteopenic effects of low-dose radium, even in the short-lived species 224Ra. It also provides a method of quantifying the osteopenic effect of bone-seeking radionuclides. PMID- 2105155 TI - Steroid/thyroid receptor-like proteins with oncogenic potential: a review. AB - Mutated or truncated forms of certain members of the steroid/thyroid receptor superfamily have oncogenic potential. The aberrant forms compete with the normal receptor for binding to the responsive element on the DNA and thus interfere negatively with the normal transcription control mechanism. Oncogenes that arise from dominant negative mutations may therefore be called "dononcs," to distinguish them from recessive types such as that causing retinoblastoma ("renoncs"). It is possible that dononcs are also responsible for the loss of hormonal responsiveness of some tumors during progression. PMID- 2105156 TI - Biotransformation of N,N',N''-triethylenethiophosphoramide: oxidative desulfuration to yield N,N',N''-triethylenephosphoramide associated with suicide inactivation of a phenobarbital-inducible hepatic P-450 monooxygenase. AB - Oxidative metabolism of the polyfunctional alkylating agent N,N',N'' triethylenethiophosphoramide (thio-TEPA) was studied in isolated rat liver microsomes and purified, reconstituted cytochrome P-450 (P-450) enzyme systems in order to elucidate the pathways of drug oxidation and to identify the possible contributions of individual P-450 enzymes to the bioactivation of this chemotherapeutic agent. Rat liver microsomes were found to catalyze conversion of thio-TEPA to its oxo metabolite, N,N',N''-triethylenephosphoramide (TEPA), in a P 450-dependent reaction that was markedly stimulated by prior in vivo treatment with drug inducers of hepatic P-450 subfamily IIB (phenobarbital), but not by pretreatment with inducers of P-450 subfamilies IA (beta-naphthoflavone) or IIE (isoniazid). Thio-TEPA depletion and TEPA formation catalyzed by phenobarbital induced liver microsomes were both inhibited by greater than 90% by antibodies selectively reactive with P-450 PB-4 (gene product IIB1), the major phenobarbital inducible rat liver microsomal P-450 form, but not by antibodies inhibitory toward 7 other rat hepatic P-450s. Oxidation of thio-TEPA to TEPA was also catalyzed by purified P-450 PB-4 (Km (app) 19 microM; Vmax (app) = 11 mol thio TEPA metabolized/min/mol P-450 PB-4) following reconstitution of the cytochrome with NADPH P-450 reductase in a lipid environment. Metabolism of thio-TEPA by P 450 PB-4 was associated with a suicide inactivation of the cytochrome characterized by kinactivation = 0.096 min-1, KI = 24 microM, and a partition ratio of 136 +/- 28 (SD) mol thio-TEPA metabolized/mol P-450 inactivated. The thio-TEPA metabolite TEPA, however, did not inactivate the cytochrome, nor was it subject to further detectable metabolism. In microsomal incubations, metabolism of thio-TEPA led to the inactivation of P-450 PB-4 (steroid 16 beta-hydroxylase) as well as P-450 IIIA-related enzymes (steroid 6 beta-hydroxylase) and the P-450 independent enzyme steroid 17 beta-hydroxysteroid:NADP+ 17-oxidoreductase, as demonstrated by use of the P-450 form-selective steroidal substrate androst-4-ene 3,17-dione. In contrast, little or no inactivation of microsomal P-450 IIA related enzymes (steroid 7 alpha-hydroxylase) or microsomal NADPH P-450 reductase was observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2105157 TI - Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice. AB - This investigation studied the effect of topical application of apigenin on skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) in SENCAR mice. Apigenin was a potent inhibitor of epidermal ornithine decarboxylase induction by TPA in a dose dependent manner from 1 to 20 mumol. Two tumorigenesis studies were conducted. In the first study, 20 mumol of apigenin was applied topically and no effect on body weight was observed. By week 33 after DMBA initiation, 48% of DMBA/TPA-treated mice developed carcinomas, while none occurred in DMBA/apigenin/TPA-treated groups. In the second study, doses of 5 and 20 mumol of apigenin were used. The papilloma incidence for 0, 5, and 20 mumol apigenin at 26 weeks after DMBA was 93.3, 58, and 39.3%, and papilloma numbers per mouse were 7.5, 2.5, and 1.8, respectively. Apigenin prolonged by 3 weeks the latency period of tumor appearance. In addition, apigenin significantly inhibited the incidence of carcinoma and the numbers of carcinomas. The incidence of carcinomas per tumor bearing animal and the ratio of carcinomas/papillomas in two apigenin-treated groups decreased although there were no significant differences between the three groups. These data indicate that apigenin inhibited skin papillomas and showed the tendency to decrease conversion of papillomas to carcinomas. PMID- 2105158 TI - Effect of cellular density and viral oncogenes on the major histocompatibility complex class I antigen response to gamma-interferon in BALB-c/3T3 cells. AB - Cellular density in culture has profound effects on major histocompatibility complex (MHC) class I antigen expression in BALB/c-3T3 cells. Cells which have been confluent for greater than 24 h demonstrate a 2- to 6-fold increase in MHC class I antigen expression compared to subconfluent cells. These density associated changes in MHC class I antigen expression occur both in untransformed and in v-mos or v-rasKi-transformed cells. The density-associated increases are specific for MHC class I antigens and do not occur with the cytoskeletal antigen actin. Transformation of the BALB/c-3T3 cells by either v-rasKi or v-mos has little or no direct effect on MHC class I expression under standard culture conditions. However, both oncogenes can indirectly alter the enhancement of MHC class I antigen expression in response to gamma-interferon. Incubation of untransformed BALB/c-3T3 cells with gamma-interferon leads to greater relative and absolute increases in MHC class I antigen expression in confluent cells than it does in subconfluent cells. In contrast, in v-rasKi- and v-mos-transformed cells, the subconfluent cells have a greater increase in MHC class I antigen expression in response to gamma-interferon than the cells which have exceeded monolayer confluence. The dense v-rasKi- and v-mos-transformed BALB/c-3T3 cell cultures are able to deplete their medium of the exogenous gamma-interferon, and this depletion of gamma-interferon causes the increase in the MHC class I antigen expression to be less sustained with lower peak expressions than the expression found in subconfluent cells. Supplementation with additional gamma-interferon can restore the full enhancement of MHC class I antigen in the transformed BALB/c-3T3 cells. The v-mos- and v-rasKi-transformed cells are more likely to deplete their medium of exogenous gamma-interferon because these cells can exceed monolayer confluence and thus achieve 10-fold higher densities than the untransformed BALB/c-3T3 cells. At high cellular densities, untransformed cells can partially deplete their medium of exogenous gamma-interferon, but this phenomenon is generally less pronounced than in the transformed cells. PMID- 2105159 TI - Species susceptibility to aflatoxin B1 carcinogenesis: comparative kinetics of microsomal biotransformation. AB - The biotransformation of the potential human carcinogen aflatoxin B1 (AFB1) was studied using hepatic microsomes from the rat, mouse, monkey, and human. Initial rates of AFB1 oxidation to aflatoxins Q1, M1, and P1, as well as the reactive intermediate AFB1-8,9-epoxide, were determined using a high performance liquid chromatography assay. The rates of generation of these AFB1 metabolites were investigated at low substrate concentrations (more representative of environmental exposures) and also at high ("saturating") concentrations commonly utilized in studies in vitro. Striking differences in ratios of the metabolites were observed. At an AFB1 concentration of 124 microM, mouse and monkey microsomes had the highest rates of AFB1-8,9-epoxide formation. Primate liver microsomes formed aflatoxin Q1 in large amounts but failed to produce detectable aflatoxin P1. Determination of the rates of formation over initial AFB1 concentrations ranging from 15 to 475 microM revealed that the proportion converted to AFB1-8,9-epoxide increased at lower substrate concentrations in the case of the rat and human microsomes but not with mouse or monkey microsomes. The differences in patterns of metabolite formation with varying concentrations have implications for interspecies comparisons of carcinogenic potency of AFB1. PMID- 2105160 TI - Sensitivity of subpopulations of mouse skin papillomas to malignant conversion by urethane or 4-nitroquinoline N-oxide. AB - Papillomas induced in SENCAR mice by initiation with 7,12 dimethylbenz(a)anthracene and promotion by treatment for 10-12 weeks with 12-O tetradecanoylphorbol-13-acetate (TPA) convert to malignancy at a low frequency. The rate of malignant conversion can be increased by either (a) promoting with TPA for a shorter duration or (b) treatment of papilloma-bearing mice with certain genotoxic chemicals, such as 4-nitroquinoline N-oxide (4-NQO) or urethane. The spontaneous conversion rate of papillomas promoted by 5 weeks of TPA exposure is severalfold higher than that of papillomas arising later during TPA promotion. Here, we compared the sensitivity to the converting agents 4-NQO and urethane of papillomas promoted by TPA for either 5, 10, or 20 weeks. In the mice promoted for 5 weeks with TPA, the already high spontaneous conversion frequency was increased 2.5 times by 4-NQO. A 2-fold increase was found after 10 weeks of TPA promotion. In contrast, no increase was seen with 4-NQO exposure begun after 20 weeks of TPA promotion. Similar results were found with urethane as converting agent. The sensitivity of the papillomas induced by short-term TPA treatment to induced conversion remains high even after a 16-week period without TPA treatment; when urethane exposure was delayed until week 21 after TPA promotion for weeks 1-5, a 2.4-fold increase in the conversion frequency was observed. PMID- 2105161 TI - Characterization of adenocarcinomas of the dorsolateral prostate induced in Wistar rats by N-methyl-N-nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2' dimethyl-4-aminobiphenyl, following sequential treatment with cyproterone acetate and testosterone propionate. AB - Carcinomas of the rat prostate induced by a single injection of N-methyl-N nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2'-dimethyl-4-aminobiphenyl, after sequential treatment with cyproterone acetate and testosterone propionate, were evaluated as potential animal models for prostatic cancer. All ten carcinomas examined were located in the dorsolateral prostate region and did not involve the distal parts of the seminal vesicles and coagulating glands. The incidence of urinary obstruction leading to the animals' death was 6 of 10 rats, and metastases in the lung, abdominal lymph nodes, and/or liver also occurred in 6 of 10 rats. The tumors were invasive adenocarcinomas, showing frequent perineural invasion and a variable degree of differentiation. There were ultrastructural similarities with human prostatic carcinomas, such as intracellular lumina. Plasma acid phosphatase was increased. Enzyme histochemical analysis revealed similarities with the Dunning R3327H and -HI prostatic carcinomas but was not helpful in determining the site of origin of the tumors. The gross and microscopic appearance of the tumors and the observation of preneoplastic lesions exclusively located in the dorsolateral prostate suggest this lobe as site of origin of the carcinomas. Preneoplastic lesions (n = 9) included atypical hyperplasias (n = 5) and lesions with all histological characteristics of carcinoma except for local invasion and metastases, which were classified as carcinoma in situ (n = 4). Although androgen sensitivity could not be assessed, the observed characteristics of the tumors [their long latency time (46-80 weeks), the presence of preneoplastic lesions, and the short duration of the treatment, leaving the animals intact] all indicate that the present approach is a valid animal model for the study of prostatic carcinogenesis. PMID- 2105162 TI - Cancer-associated galactosyltransferase as a new tumor marker for ovarian clear cell carcinoma. AB - Serum cancer-associated galactosyltransferase antigen (caGT) was assayed in gynecological cancer patients by means of a GT-II-reactive monoclonal antibody (MAb 3872)-based immunoassay. Thirty-six of 47 (75%) ovarian cancer patients showed a significant elevation of caGT in serum above the cutoff level of 200 milliunits/ml (mean +/- 2 SD) determined from normal controls. Particularly, serum caGT levels in eight of nine patients with ovarian clear cell carcinoma were above the cutoff value, and six of them gave more than 200 milliunits/ml. Elevation of caGT in serum from pregnant women was also detected, and the level increased during the course of gestation. Immunohistochemical study revealed that not only various ovarian carcinoma cells in vivo and in vitro, but also syncytiotrophoblast of early gestational placenta, fetal tissues such as mucus producing cells in the lower alimentary tract, and renal tubules at the 11th week of gestation were stained with MAb 3872, thus indicating its oncofetal character. Compared with CA-125, caGT showed a lower false-positive rate (10%) in benign gynecological diseases, and there was no correlation between caGT and CA-125 values. Therefore, caGT will be a useful tumor marker for ovarian cancers, especially for clear cell carcinoma. PMID- 2105163 TI - DNA adduct formation in mouse tissues in relation to serum levels of benzo(a)pyrene-diol-epoxide after injection of benzo(a)pyrene or the diol epoxide. AB - Previous studies have shown that the carcinogenic metabolite of benzo(a)pyrene [B(a)P], B(a)P-7,8-diol-9,10-epoxide (BPDE), is transported in serum after B(a)P injection in mice. It is possible that serum transport is an important source of carcinogenic metabolite and results in DNA adduct formation in tissues. This possibility was studied by comparing the time course for BPDE appearance in serum with that for BPDE/DNA adduct formation after B(a)P i.p. injection (2, 20, or 200 mg/kg) into female C57BL/6 x C3H F1 mice. Additionally, BPDE was injected i.v. (8.25 nmol), and its disappearance from serum and adduction of tissue DNA were followed. BPDE serum levels and DNA adduct levels were measured by 32P postlabeling analysis. Results indicate that, after a 200-mg B(a)P/kg i.p. injection, BPDE/DNA adduct levels rose sharply in liver, lung, kidney, stomach, and spleen through 5 h and then more gradually through 24 h. Adduct levels were similar in all tissues at 24 h. BPDE levels in serum reached a plateau within 2.5 h and remained constant thereafter (10 to 11 nM). B(a)P levels in serum fell steadily from 1980 nM at 1 h to 350 nM by 24 h. Levels of serum BPDE and DNA adducts showed a similar dose dependency at 10- and 100-fold lower B(a)P i.p. doses. After BPDE i.v. injection, BPDE levels in serum decreased to 0.16% of the initial level within 5 min. By this time, BPDE/DNA adducts were at peak levels in all tissues assayed. Lung adduct levels were 10 to 100 times greater than those in the other tissues. These results support a role for serum transport of BPDE in the production of DNA adducts after B(a)P since BPDE was available in serum throughout the time course for DNA adduct formation. Further, injected BPDE rapidly formed DNA adducts and this occurred primarily in the lung, which had the greatest access to the transported carcinogen. PMID- 2105164 TI - Activity of methylated forms of selenium in cancer prevention. AB - The anticarcinogenic activity of selenium in animal models is well established. The active forms of selenium involved have not been identified to date, but conversion of selenium via hydrogen selenide (H2Se) to methylated forms such as dimethylselenide and trimethylselenonium ion is an important metabolic fate. By controlling the entry of selenium into various points within this pathway through selection of appropriate starting compounds, it is possible to pinpoint more closely the form(s) of selenium responsible for its anticarcinogenic activity. Selenobetaine in the chloride form [(CH3)2Se+CH2COOH] and its methyl ester are extensively metabolized in the rat to mono-, di-, and trimethylated selenides, largely bypassing the inorganic H2Se intermediary pool. The chemopreventive efficacy of these selenobetaines was determined at 1 and 2 ppm selenium supplemented in the diet throughout the duration of the experiment using the dimethylbenz(a)anthracene induced mammary tumor model in rats. There was a dose dependent inhibitory response to both compounds, and they appeared to be slightly more active than selenite. These doses were without any adverse effects on the animals. Coadministration of selenobetaine with arsenite (5 ppm arsenic) enhanced the tumor-suppressive effect of selenobetaine, although arsenic by itself was totally inactive. Arsenite is known to inhibit certain steps in selenium methylation. The substantial prophylactic efficacy of methylated selenides and the enhancement by arsenite suggest that partially methylated forms of selenium may be directly involved in the anticarcinogenic action of selenium. PMID- 2105165 TI - Localization of growth hormone-releasing factor-like immunoreactivity in the hypothalamo-hypophysial system of some teleost species. AB - An antiserum to growth hormone-releasing factor (GRF) 1-44 was applied on brain and pituitary sections of nine teleost species. Immunoreactive (ir) perikarya were demonstrated in parvo- and magnocellular portions of the preoptic nucleus (PON) and occasionally in the nucleus lateralis tuberis. The two tracts originating in the PON ran ventro-laterally toward the optic chiasm and then caudally in the basal hypothalamus. In the pars distalis (PD) of the eel, carp, goldfish and salmonids, GRF-ir fibers did not enter the rostral PD and few fibers passed close to somatotropes. In Myoxocephalus and Mugil, a variable number of ir fibers passed close to cells of the rostral and proximal PD. In the neurointermediate lobe, GRF-ir fibers were located exclusively in the neural tissue of the eel and trout. In goldfish, carp and Myoxocephalus, GRF-ir fibers entered the intermediate lobe. This antiserum also labeled corticotrops and, to a lesser extent, melanotrops in the pituitary of cyprinids. A variable number of perikarya contained both GRF and vasotocin in the PON of the eel. In all teleost species studied so far, the distribution patterns of GRF are different, and the function of the various adenohypophysial cell types appears to be differently modulated, according to the variable distribution of GRF in the pituitary. PMID- 2105166 TI - The Drosophila seven-up gene, a member of the steroid receptor gene superfamily, controls photoreceptor cell fates. AB - The Drosophila seven-up (svp) gene was isolated as a lethal insertion in an "enhancer trap" screen. It is expressed and required in photoreceptor cell precursors R1, R3, R4, and R6 during eye development. The absence of svp+ function causes a transformation of these cells toward an R7 cell fate, as judged by morphology and expression of an R7-specific marker. This transformation depends in part on the sevenless gene product. Our results show that svp is involved in control of cell fate during the generation of neuronal diversity. Molecular analysis of svp reveals that it is a member of the steroid receptor gene superfamily and is likely to be a Drosophila homolog of the human transcription factor COUP. PMID- 2105167 TI - Reactivity of lymphocytes to a progesterone receptor-specific monoclonal antibody. AB - In this study we present evidence for reactivity of pregnancy lymphocytes, but not nonpregnancy lymphocytes, with the progesterone receptor-specific monoclonal antibody mPRI. Using an avidin-biotin peroxidase detection system, we found a nuclear staining in 14.6 +/- 3.7% (mean +/- SEM, N = 27) of pregnancy lymphocytes, while only 0.47 +/- 0.33% (mean +/- SEM, N = 15) of nonpregnancy lymphocytes reacted with the antibody. To characterize the receptor-bearing subset, CD8+ and CD4+ cells were depleted by complement-dependent lysis. Depletion of CD8+ cells was accompanied by 62 +/- 18% loss of progesterone receptor-bearing cells, while depletion of CD4+ cells resulted in a twofold increase in the number of positively staining lymphocytes. In nonpregnancy lymphocytes a 3-day PHA treatment, as well as allogeneic stimulation, resulted in a significant increase in the number of receptor-containing cells. These results suggest that pregnancy, but not nonpregnancy, lymphocytes contain progesterone binding structures, and that these are inducible by mitogenic or alloantigenic stimuli. PMID- 2105168 TI - 1,25-Dihydroxyvitamin D3 modulates the effects of interleukin 2 independent of IL 2 receptor binding. AB - Previous studies have shown that 1,25-dihydroxyvitamin D3 (calcitriol) is a macrophage-derived cytokine and a potent inhibitor of IL-2 and interferon-gamma (IFN-gamma) production and T lymphocyte proliferation. The growth inhibitory effect of calcitriol is only partially reversed by IL-2 addition, suggesting IL-2 independent effects. In this report we characterize the IL-2-independent effects of calcitriol on lymphocyte activation. Calcitriol inhibited cellular transition from early to late G1 (G1A-G1B transition) in both the absence and presence of IL 2. Exogenous IL-2 did not increase either IFN-gamma production or transferrin receptor (TfR) expression in the presence of calcitriol despite increases in cell entry into late G1 and proliferation. Calcitriol treatment reduced TfR expression by activated T lymphocytes independent of their location in the cell cycle, further suggesting its independence from IL-2-mediated events. Combinations of rIL-2 and rIL-4 did not reverse calcitriol-dependent inhibition of proliferation and TfR expression to any greater degree than rIL-2 alone. Northern blot analysis demonstrated the decrease in IFN-gamma and TfR mRNA accumulation with calcitriol treatment was unaffected by exogenous IL-2. In contrast, IL-2R mRNA and protein were increased by IL-2, with superinduction in the presence of calcitriol, demonstrating that the lack of effect on IFN-gamma and TfR was not due to IL-2 insensitivity. Moreover, equivalent numbers of high-affinity IL-2R were expressed by both control and calcitriol-treated T lymphoblasts. Thus, lectin-activated T lymphocyte responsiveness to IL-2, as measured by IL-2R expression and proliferation, can be partly to completely dissociated from IFN-gamma production and TfR expression in the presence of calcitriol. Finally, IL-2-induced proliferation of unstimulated mononuclear cells and purified T lymphocytes was inhibited by calcitriol. These data indicate that local production of calcitriol by activated macrophages is capable of regulating T lymphocyte activation not only through suppression of IL-2 production, but also through additional mechanism(s), that are mediated at a post-IL-2R level. PMID- 2105169 TI - Frequency analysis of CD4+CD8+ T cells cloned with IL-4. AB - The coexpression of both CD4 and CD8 molecules on T cells occurs in the peripheral blood at a low frequency and can be generated transiently on CD4+ peripheral blood T cells by treatment with lectin which induces CD8 biosynthesis and cell surface expression. We have cloned T cells in a nonselective fashion from normal subjects in the presence of either IL-2, rIL-4 and IL-2, or rIL-4 and have examined the phenotypic expression of CD4 and CD8. The addition of excess rIL-4 increased the expression of CD8 on the surface of CD4+ T cell clones but did not increase CD4 expression on CD8+ T cell clones. There were three patterns of CD4 and CD8 expression observed: high density CD8 with no CD4 expression; high density CD4 with low CD8 expression; or high density CD4 with higher cell surface CD8 expression which was regulated by the presence of rIL-4. CD4+ T cell clones originally cultured in IL-2 and rIL-4 and subsequently grown in IL-2 alone exhibited decreased expression of the CD8 molecule. The increased expression of CD8 did not correlate with NK activity or lectin-dependent cytotoxicity in an antigen independent system. In addition, rIL-4 alone or in combination with IL-2 appeared to accelerate the growth curve of T cell clones as compared to IL-2 alone. These results show that IL-4 can upregulate CD8 expression on CD4+ T cell clones while not effecting CD4 expression on CD8+ T cell clones. As class I MHC is the ligand for the CD8 molecule, expression of CD8 induced by IL-4 on CD4+ T cells may allow for increased nonspecific cell to cell contact during the course of an inflammatory response. PMID- 2105170 TI - Reduction of ischemic K+ loss and arrhythmias in rat hearts. Effect of glibenclamide, a sulfonylurea. AB - Glibenclamide, one of the antidiabetic sulfonylureas, is known to block ATP dependent K+ channels. We used this drug to determine to what extent K+ loss from acutely ischemic myocardium is mediated via these channels. We also investigated whether glibenclamide would influence ischemic arrhythmias. Isolated rat hearts rendered globally ischemic showed no correlation between early lactate and K+ efflux rates. Cumulative K+ loss during 11 minutes of global ischemia (0.5 ml min 1 g-1) was reduced, from 3.2 +/- 0.3 to 2.5 +/- 0.1 mueq/g (p less than 0.025) by 1 microM glibenclamide and from 3.3 +/- 0.2 to 1.9 +/- 0.2 mueq/g (p less than 0.005) by 10 microM glibenclamide, while lactate efflux was unaltered by the drug. Glibenclamide also exhibited potent antifibrillatory activity, abolishing irreversible ventricular fibrillation during regional ischemia (0/6 vs. 5/6 controls; p less than 0.02) and during global ischemia (0/7 vs. 9/9 controls; p less than 0.01). Heart rate, coronary flow rate, peak systolic pressure, and myocardial oxygen consumption were unaltered by the drug (1 microM). Similarly, glibenclamide (1 microM) did not alter myocardial ATP, phosphocreatine or lactate content, or glucose utilization. Ventricular fibrillation threshold during normoxia was also unaltered by glibenclamide (1 microM). We conclude that K+ loss during acute myocardial ischemia is mediated partly by ATP-dependent K+ channels, and not by a tightly coupled co-efflux with anionic lactate. PMID- 2105171 TI - Aspirin and prostacyclin synthesis in humans. PMID- 2105172 TI - An analysis of the cost effectiveness of the implantable defibrillator. AB - The automatic implantable defibrillator has been shown to decrease the mortality of patients who have survived cardiac arrest due to ventricular tachycardia or fibrillation and are at high risk for recurrence. We performed a cost effectiveness analysis of this seemingly expensive new technology with data obtained from the 1984 Medicare data base, the medical literature, Medicare carriers, individual pharmacies and hospitals, and expert opinion. Analyzing combinations of principal and secondary discharge diagnoses across 18 diagnosis related groups, we estimated the cost of hospitalization for a comparison group of patients. Hospitalization costs for the defibrillator group were obtained from reported empirical data. Rehospitalization rates and other health-care use estimates were solicited from an expert panel of physicians, and mortality rates for both groups were obtained from the literature. Using a decision-analytic model, we estimated that the net cost effectiveness of the defibrillator, when used in the high-risk patient, is approximately $17,100 per life-year saved, with sensitivity analyses suggesting that the true value lies between $15,000 and $25,000. This estimate is well within the range that is currently accepted by the US medical care system for other life-saving interventions. We also estimated the cost effectiveness of the defibrillator in a 1991 scenario to be $7,400 per life year saved, when the device would have greater longevity, would be programmable, and would not require a thoracotomy. Sensitivity analyses suggest that the true value lies between a value that is cost saving (less expensive than pharmacologic therapy) and $19,600 per life-year saved. PMID- 2105173 TI - Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment. Possible role of early coronary atherosclerosis. AB - We examined the response of left coronary arteries to intracoronary injection of acetylcholine (ACh) 50 micrograms in 74 patients by measuring the diameter changes with a videodensitometric analysis system. Patients with angiographically normal coronary arteries were subdivided into a younger group of 26 patients (age, 9-29 years) and an older group of 23 patients (age, 31-68 years). In the younger group, the diameter at the distal segment of the left anterior descending artery (LAD) and at the proximal, middle, and distal segments of the left circumflex artery (LCx) increased significantly (16.7 +/- 19.3%, p less than 0.01, for LAD and 8.0 +/- 18.8%, p less than 0.05; 11.0 +/- 16.1%, p less than 0.01; and 19.8 +/- 17.5%, p less than 0.01, for LCx segments, respectively) in response to ACh. In the older group, on the other hand, the diameter at the proximal and middle segments of LAD and LCx decreased significantly (-20.8 +/- 16.9%, p less than 0.01; and -17.9 +/- 28.4%, p less than 0.01, for LAD segments and -14.6 +/- 17.4%, p less than 0.01; and -11.3 +/- 21.4%, p less than 0.05, for LCx segments, respectively). The dilator response to ACh in the younger group was significantly greater in the distal segment than in the proximal segment in both LAD and LCx (p less than 0.01 for LAD and p less than 0.05 for LCx). The constrictor response to ACh in the older group was significantly greater in the proximal than the distal segment in both LAD and LCx (p less than 0.05 for LAD and LCx, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105174 TI - Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. AB - In animals, acetylcholine dilates normal arteries and produces vasoconstriction in the presence of hypercholesterolemia, hypertension, or atherosclerosis, reflecting endothelial cell dysfunction. In patients with angiographically smooth coronary arteries, acetylcholine has been reported to produce both vasodilation and constriction. To test the hypothesis that the acetylcholine response relates to risk factors for coronary artery disease, acetylcholine 10(-8) to 10(-6) M was infused into the left anterior descending or circumflex coronary artery, and diameter changes were assessed with quantitative angiography in 34 patients with angiographically smooth coronary arteries. The acetylcholine response ranged from +37% (dilation) to -53% (constriction) at the peak acetylcholine dose. All coronary arteries dilated in response to nitroglycerin (26 +/- 17%), suggesting an abnormality of endothelial function in the patients with a constrictor response to acetylcholine. By multiple stepwise regression analysis, serum cholesterol (p less than 0.01), male gender (p less than 0.001), family history (p less than 0.05), age (p less than 0.05), cholesterol level (p less than 0.01), and total number of risk factors (p less than 0.0001) were independently associated with the acetylcholine response. Thus, coronary risk factors are associated with loss of endothelium-dependent vasodilation. The development of vasoconstriction is likely to be an abnormality of endothelial function that precedes atherosclerosis or an early marker of atherosclerosis not detectable by angiography. PMID- 2105175 TI - Antiplatelet antibody [7E3 F(ab')2] prevents rethrombosis after recombinant tissue-type plasminogen activator-induced coronary artery thrombolysis in a canine model. AB - Coronary artery rethrombosis can complicate initially effective thrombolytic therapy. Platelets interacting with injured vascular endothelium in a region along the coronary artery with reduced luminal cross-sectional area contribute to rethrombosis. The purpose of this study was to investigate the potential of the F(ab')2 fragment of the murine monoclonal antibody 7E3 [7E3 F(ab')2] to prevent rethrombosis after intracoronary clot lysis with recombinant tissue-type plasminogen activator (rt-PA) in an experimental model. The 7E3 F(ab')2 binds to the platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa), thereby preventing platelet-fibrinogen interaction and intravascular thrombus formation. Experimental coronary artery thrombosis was produced in the anesthetized dog by application of direct anodal current to the intimal surface of the left circumflex coronary artery in the region of an external stenosis. Lysis of the established intracoronary thrombus was achieved with the intravenous administration of rt-PA (25 mg) after which the animals were randomized into two groups. Group 1 (n = 10) served as the control, receiving the saline diluent, and group 2 (n = 9) received 7E3 F(ab')2, given as a single intravenous injection (0.8 mg/kg). The times required for occlusive thrombus formation, rt-PA-induced thrombolysis, and rethrombosis (if it occurred) were similar in the animals treated with saline and those treated with 7E3 F(ab')2. The initial left circumflex coronary artery blood flow was similar in both groups but decreased to a negligible level in group 1. In group 2, left circumflex coronary artery blood flow declined modestly (24 +/- 2 to 10 +/- 2 ml/min). Rethrombosis occurred in all animals in group 1 but in only two of nine animals in group 2 (p less than 0.05). Oscillations in coronary blood flow preceded rethrombosis in group 1, whereas 7E3 F(ab')2 stabilized left circumflex coronary artery blood flow patterns during the course of teh experimental protocol (5.2 +/- 0.9 vs. 0.7 +/- 0.4 oscillations, respectively; p less than 0.05). Thrombus mass recovered from the left circumflex coronary artery at the conclusion of each experiment was greater in group 1 as compared with group 2 (7.0 +/- 2.3 vs. 1.5 +/- 0.7 mg, respectively; p less than 0.05). The area of left ventricle at risk for infarction was similar in both groups but infarct size, infarction/at risk assessed histochemically, was larger in group 1 than group 2 (35 +/- 9% vs. 6 +/- 4%, respectively; p less than 0.05). Platelet aggregation induced by ADP and arachidonic acid was similar at baseline for all of the animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2105177 TI - More pitfalls in human plasma amino acid analysis. PMID- 2105176 TI - Immunohistochemical localization of guanine nucleotide-binding proteins in rat olfactory epithelium during development. AB - It has recently been proposed that guanine nucleotide (GTP)-binding proteins (G proteins) are involved in transducing stimuli in olfactory receptor neurons. If this is the case, G-proteins should be expressed when receptor cells first generate action potentials in response to odorants, i.e. in the rat fetus on the 16th embryonic day (E16). We have done an immunohistochemical study to determine when the alpha- and beta-subunits of the stimulatory G-protein (Gs), are expressed in developing rat olfactory epithelium. The 3 primary antisera used were monospecific polyclonal antibodies generated in rabbits by immunization with synthetic peptides, the amino acid sequences of which matched a portion of the alpha- or beta-subunits of stimulatory G-protein. Both subunits were present in olfactory axons at E15 and in olfactory receptor cell cilia at E16, the day when cilia first sprout in these cells. As development progressed and more cilia grew, most were immunoreactive with antisera to both subunits. Examination of specimens with electron microscopic immunocytochemistry confirmed the localization. Not all cilia on a given olfactory cell were stained, in either fetal or juvenile specimens. The observation that G-proteins are expressed in cilia when action potentials are first demonstrated supports the hypothesis that G-proteins are involved in signal transduction in olfactory receptor cells. PMID- 2105178 TI - "Hook-effect" in a patient with a gonadotropin-secreting tumor. PMID- 2105179 TI - Competitive binding enzyme immunoassay for zonisamide, a new antiepileptic drug, with selected paired-enzyme labeled antigen and antibody. AB - We assessed the competitive binding between zonisamide (ZNS) in serum samples and beta-galactosidase-labeled ZNS derivatives, using competing antibodies to ZNS derivatives, and selected the best enzyme-labeled antigen and antibody for accurate enzyme immunoassay (EIA) of ZNS in serum without interference from its metabolites or from other antiepileptic drugs. This EIA, based on use of antibody linked to bacterial cell walls, has advantages over HPLC in simplicity, speed (50 samples per hour), and lack of requirement for special equipment. The concentrations of ZNS in serum as measured by the EIA correlated well with those by HPLC (n = 33, r = 0.977). PMID- 2105180 TI - Quantitative immunoenzymatic assay of human lutropin, with use of a bi-specific monoclonal antibody. AB - In this immunoenzymatic assay for human lutropin (hLH) we used bi-specific antibodies (BiAbs) obtained from the fusion of two hybridomas producing antibodies to beta-D-galactosidase and hLh. The BiAb complexed with the enzyme beta-D-galactosidase was used as tracer in a double-determinant assay. We compared the assay involving the BiAb (Bi-EIA) with an immunoenzymatic assay (EIA) in which the same capture antibody was used but the tracer was an enzyme conjugated hLH-specific monoclonal antibody produced by the same parental cell line used to produce the BiAb. The coefficient of correlation (r) between the two assays was 0.979 but the Bi-EIA was more sensitive (detection limits: 0.8 int. units/L for the Bi-EIA, 2.0 int. units/L for the EIA) and more specific (less than 0.04% vs less than 1.2% cross-reactions with human choriogonadotropin). Mean intra- and interassay CVs for the Bi-EIA were 2.9% and 5.9%, respectively. Correlation (r) with an immunoradiometric assay (IRMA, Serono kit) was 0.960, with radioimmunoassay (RIA, Biodata kit) 0.909, and with an enzyme-linked immunosorbent assay (ELISA kit, Specialty Medical Industries Inc.) 0.888, (n = 25). Evidently, bi-specific antibodies can be used successfully in immunoenzymatic assays, and with potentially greater sensitivity and specificity than assay with a traditional antibody-enzyme conjugate. PMID- 2105181 TI - Low-frequency positive-pressure ventilation with extracorporeal carbon dioxide removal. AB - Successful use of a new technique, low-frequency positive-pressure ventilation with extracorporeal CO2 removal (LFPPV-ECCR) is presented. The association of fulminant respiratory failure with CNS hemangioblastoma, described in the present patient, has been reported only once before, in 1928. PMID- 2105182 TI - Nutritional immunomodulation in burn patients. AB - A series of laboratory experiments in thermally injured guinea pigs has shown that feeding by the enteral route immediately after injury results in a decreased metabolic response by preventing loss of the GI barrier to the entrance of intestinal endotoxin and bacteria. Feeding by the iv route or giving crystalline amino acids instead of intact protein does not prevent atrophy of the intestine, nor does it prevent the hypermetabolic response. Optimal diets for nutritional support of burn patients contain 20% of energy from whey protein, 2% from arginine, 0.5% from cysteine, and 0.5% from histidine. Lipids comprise 15% of nonprotein calories with 50% fish oil (high in omega-3 fatty acids) and 50% safflower oil (high in linoleic acid). In a prospective clinical study, administration of this new diet was found to reduce wound infection (p less than .03), shorten hospital stay (p less than .02), and reduce death (p less than .06) when compared to other standard enteral formulations. PMID- 2105183 TI - Nutritional pharmacology: its role in the hypermetabolism-organ failure syndrome. PMID- 2105184 TI - Effect of dietary protein and amino acids on immune function. AB - The normal immune system has local and systemic components which are influenced by a variety of alterations. Impaired host immunity is associated with neoplasia, protein calorie malnutrition, and the administration of immunosuppressive drugs. It is well accepted that protein calorie malnutrition impairs host immunity with particular detrimental effects on the T-cell system, resulting in increased opportunistic infection and increased morbidity and mortality in hospitalized patients. Individual nutrient substrates may also have a major influence on the immune system. Individual amino acids are often described as essential, based on requirements for optimal growth and maintenance of positive N balance. Arginine has been demonstrated to be essential to the traumatized host and may have tissue specific properties which influence components of the immune system. Thus, arginine may be of value in clinical situations where the immune system is compromised. In a series of experiments in normal animals, arginine was demonstrated to enhance cellular immune mechanisms, in particular T-cell function. It also has a marked immunopreserving effect in the face of immunosuppression induced by protein malnutrition and increases in tumor burden. In postoperative surgical patients, arginine supplementation results in enhanced T-lymphocyte response and augmented T-helper cell numbers, with a rapid return to normal of T-cell function postoperatively compared with control patients. These data suggest that arginine supplementation may enhance or preserve immune function in high-risk surgical patients and theoretically improve the host's capacity to resist infection. PMID- 2105185 TI - Dietary lipids, eicosanoids, and the immune system. PMID- 2105186 TI - Electron beam irradiation for cutaneous lymphoma. PMID- 2105187 TI - Genetics of capsular polysaccharide production in bacteria. PMID- 2105188 TI - Capsular polysaccharides as vaccine candidates. PMID- 2105189 TI - Biosynthesis and genetics of C3. PMID- 2105190 TI - Bronchial response to methacholine in "healthy" children of asthmatic parents. Effect of treatment with cromolyn sodium. AB - Cumulative dose response curves to inhaled methacholine were established in 24 "healthy" children of asthmatic parents and 7 healthy children of healthy parents. Atopic children of asthmatic parents demonstrated higher bronchial hyperreactivity (BHR) than nonatopic children. The BHR was about ten times less than in the atopic parents of asthmatic children, indicating marked increase in BHR with age in atopic members of asthmatic families. Six weeks of treatment with cromolyn sodium (disodium cromoglycate) decreased BHR significantly (p less than 0.05) in eight atopic children, while no change occurred in BHR in five nonatopic children. PMID- 2105191 TI - Clinical efficacy and cost benefit of pulse flow oxygen in hospitalized patients. AB - Pulse flow oxygen administered during early inspiration is a promising approach to oxygen conservation. Previous short-term studies show equivalent arterial PO2, 55 to 60 percent oxygen savings, and no reduction of nasal humidity when compared with continuous flow nasal cannula oxygen. This study compares the clinical efficacy of pulse flow and continuous flow oxygen in 100 patients recently hospitalized for diseases requiring O2 therapy. In an unblinded crossover design, pulse and continuous O2 were administered alternately during four 51/2-hour periods. Oxygen saturation was monitored continuously during the 23-hour study. Mean SaO2 on pulse flow (95.6 +/- 2.7 percent) was clinically the same as continuous flow (95.3 +/- 2.6 percent). Mean SaO2 on pulse flow during the 30 minutes before or after each crossover (95.5 +/- 3.3 percent) was similar to continuous flow during the 30 minutes near crossover (95.3 +/- 3.1 percent). It is concluded that the two delivery systems produce similar levels of SaO2 over the course of a day and night. Analysis of potential cost savings achieved by use of the device for a 350-bed hospital suggests a savings of about $50,000 yearly when accompanied by termination of oxygen humidification. PMID- 2105192 TI - Detection of antibodies against Mycobacterium tuberculosis. PMID- 2105193 TI - Drug-resistant tuberculosis in AIDS. PMID- 2105194 TI - Preoperative bowel preparation. A survey of colon and rectal surgeons. AB - A survey of 500 clinically active, board-certified colon and rectal surgeons in the United States and Canada was conducted to obtain data regarding current methods of bowel preparation for elective colorectal surgery. A review of recent publications on preoperative bowel preparation was used to compare the current literature recommendations with the actual practice among the group surveyed. Responses were received from 352 of 500 colorectal surgeons to whom questionnaires were sent (70 percent response rate). All respondents used a mechanical preparation and some form of antibiotics. The favorite antibiotic regimen was oral antimicrobials combined with systemic antibiotics (88 percent). Concomitant administration of oral neomycin-erythromycin base and a systemic second generation cephalosporin active against both anaerobic and aerobic colonic bacteria, together with oral polyethelene glycol electrolyte mechanical colonic cleansing, was the most popular method of preoperative bowel preparation (58 percent). The second most frequent method of mechanical bowel cleansing consisted of conventional enemas, dietary restrictions, and cathartic preparations (36 percent). Mannitol solution (5 percent), and whole-gut irrigation per nasogastric tube (1 percent) were the least popular methods of mechanical bowel cleansing. The literature supports the current methods of preoperative bowel preparation used by the vast majority of surgeons surveyed. PMID- 2105195 TI - Intracerebral crises during treatment of diabetic ketoacidosis. AB - Sixty-nine instances of intracerebral complications of diabetic ketoacidosis (DKA), including 29 unpublished occurrences, were analyzed to determine predictive factors, the frequency of other disorders resembling cerebral edema, the effectiveness of intervention to reduce intracranial pressure, and whether any etiologic considerations appeared valid. The review failed to implicate rate of hydration, tonicity of administered fluids, rate of correction of glycemia, or use of bicarbonate. Infants and young children (less than 5 yr of age) were disproportionately represented (33%), as were new-onset patients (62%). Approximately 20% of patients were found to have localized basilar edema, hemorrhage, thromboses, or infection by computed tomography scan or on postmortem examination. The histories of 50% of the patients suggested a period of dramatic neurological change preceding respiratory arrest (RA) during which intervention might be effective. Twenty-three patients were treated for increased intracranial pressure before RA; 13 patients survived in an independent functional state, and 3 survived in a severely disabled or vegetative state. Only 3 of the remaining 46 patients survived normally: 2 were untreated and never developed RA, and 1 was given mannitol at the onset of apnea. This review supports close neurological monitoring and intervention to reduce intracranial pressure when there are definite signs of neurological compromise. However, treatment appears to be successful in only 50% of patients who give sufficient warning for such intervention, and they comprised half of the study population. Therefore, prevention of DKA remains the most important goal to avoid intracerebral complications. PMID- 2105196 TI - Augmented polyol pathway activity and retinal pigment epithelial permeability in the diabetic BB rat. AB - In the present study we investigated the relationship between an augmented polyol pathway and the breakdown of the blood-retinal barrier in the spontaneously diabetic BB rat. Permeability experiments were performed in diabetic and age matched non-diabetic BB rats in a longitudinal fashion using horseradish peroxidase. Increased permeability of horseradish peroxidase across the retinal pigment epithelium was noted after 6 months of diabetes. Abnormalities of the basal plasmalemmal infoldings of the retinal pigment epithelium were noted in the control animals and appeared to be exaggerated in diabetic rats. Simultaneous quantitative ultrastructural immunohistochemistry, using an affinity purified anti-BB rat aldose reductase antibody and protein-A gold, revealed a significant increase in the aldose reductase immunoreactivity of the retinal pigment epithelium in diabetic animals. These findings suggest that an augmented polyol pathway activity may play a role in the pathogenesis of the blood-retinal barrier breakdown at the level of the retinal pigment epithelium in the diabetic BB rat. PMID- 2105197 TI - Topical application of the hypoglycemic agent glibenclamide and changes in blood glucose, plasma insulin (IRI) levels and plasma concentration of glibenclamide in normal rats. AB - This study was done to determine whether an oral hypoglycemic agent would be absorbed through the skin and consequently lower blood glucose levels. We applied 250 mg or 500 mg of 5% glibenclamide ointment (GO) to the cleanly shaved dorsa (5 x 10 cm) of overnight-fasted male Wistar rats, weighing 250-300 g. Blood samples were collected at 1, 3, 6, 12 and 24 h after the application of GO and blood glucose, plasma insulin (IRI) and the plasma concentration of glibenclamide were determined. The plasma concentration of glibenclamide reached a high level as early as 1 h after application and the level was maintained for 24 h. The plasma concentration of glibenclamide in the 500-mg GO group was higher than in the 250 mg GO group, but even 24 h after application the 250-mg GO group showed a mean value of 206 ng/ml. Mean blood glucose levels in both GO groups at every time point after application were significantly lower than in the control group; with respect to mean IRI levels the opposite was found. Thus, glibenclamide is absorbed through the skin and reaches a level of plasma concentration which induces significant changes in blood glucose and IRI levels. This may well be a new approach to controlling blood glucose levels in patients with diabetes mellitus. PMID- 2105198 TI - Autocrine differentiation of PC12 cells mediated by retroviral vectors. AB - Rat pheochromocytoma PC12 cells have been modified genetically by the use of replication-defective retroviral vectors containing either the bacterial gene for beta-galactosidase (lac Z) or cDNAs for mouse beta-nerve growth factor (NGF) and the bacterial gene for neomycin resistance. Using the lac Z vector, clonal lines of PC12 cells were obtained in which almost 100% of cells stably expressed this histochemical marker. Infection of PC12 cells or the derived subclone PC12-BAG, which expresses beta-galactosidase, with the NGF vectors resulted in autocrine differentiation as assessed by extensive neurite formation, which occurred within hours after infection and was maintained for weeks in culture. Neurite formation could be partially blocked by antibodies to NGF. The percentage of cells expressing neurite outgrowth was greater than that of PC12 cells treated with exogenous NGF. PC12 cells infected with the NGF vectors were shown to release this trophic factor into the medium using a two-site enzyme immunoassay and a bioassay on 'naive' PC12 cells. PC12 cells genetically modified using these vectors provide a means to: follow the fate of the cells after transplantation into animals; test for delivery in vivo of NGF and catecholamines by grafted, autocrine-differentiated PC12 cells; and study the long-term actions of NGF on responsive cells without adding exogenous NGF. PMID- 2105199 TI - [Effects of DL-difluoromethylornithine on the cell surface charge of Ehrlich ascitic cancer during different phases of the mitotic cycle]. AB - Difluoromethylornithine (DFMO)-induced polyamide deficiency has been studied for its effect on the electrophoretic mobility of the Ehrlich ascitic cells in G1, S and G2 phases of the mitotic cycle. The DFMO treatment alters the pattern of the electrophoretic mobility distribution of Ehrlich ascite cells. The most profound changes of the electrophoretic mobility pattern are observed in G1-phase and at the S phase beginning. Exogenic polyamines decrease the electrophoretic mobility of cancer cells, which is accompanied by restoration of the initial pattern of the electrophoretic mobility distribution. PMID- 2105200 TI - The prepubertal hiatus in gonadotropin secretion in the male rhesus monkey (Macaca mulatta) does not appear to involve endogenous opioid peptide restraint of hypothalamic gonadotropin-releasing hormone release. AB - To examine the possibility that the prepubertal hiatus in gonadotropin secretion in primates is occasioned by an endogenous opioid peptide (EOP)-dependent suppression of pulsatile GnRH release, the ability of an EOP receptor antagonist, naloxone (NAL), to elicit GnRH release was examined indirectly in the rhesus monkey. For this purpose, six castrated male monkeys, aged 18-24 months, first received an intermitten iv infusion of GnRH (0.1 micrograms/min for 3 min every h) to enhance the responsiveness of the gonadotroph to endogenous GnRH. Acute and chronic blockade of EOP receptors with single bolus injections of NAL at three doses (0.2, 2.0, and 10 mg/kg BW) and a continuous infusion of the antagonist (2 mg/h for 36 h), respectively, failed to elicit significant increments in circulating concentrations of mean LH. In addition, changes in plasma LH concentrations during a chronic intermitten iv infusion of NAL (2 mg/kg BW every 6 h for up to 16 days) were unremarkable. Unequivocal discharges of LH, however, were observed in response to small doses of GnRH (0.3 micrograms/monkey) administered iv after all modes of NAL administration. Taken together, these findings fail to provide evidence for the view that in primates, EOPs underlie the hiatus in pulsatile GnRH release, which in these species is responsible for the quiescence of the pituitary-testicular axis during the greater part of prepubertal development. PMID- 2105201 TI - Superovulation of ewes immunized against the human recombinant inhibin alpha subunit associated with increased pre- and postovulatory follicle-stimulating hormone levels. AB - The efficacy and specificity of human recombinant inhibin alpha-subunit as an immunogen were determined by studying its effect on the ovulation rate and serum gonadotropin levels in ewes. Beginning on July 12 (day 1 of the experiment), 2-yr old Rambouillet ewes were immunized four times at intervals of 20, 30, and 30 days, respectively, by im injections of the alpha-subunit each time with 100 micrograms. Blood was collected from the jugular vein as required before and after ovulation. Ovulation rates were determined, beginning on day 87, by laparotomy before estrous synchronization by means of vaginal progestagen sponges. After synchronization, ewes were examined again. The ovulation rate before estrous synchronization was over 4 times higher in immunized than control ewes [8.7 +/- (+/- SE) 1.9 vs. 2.0 +/- 0.0]. After estrous synchronization, ovulation rates in the immunized and control ewes were 6.3 +/- 2.4 and 1.3 +/- 0.3, respectively; this increase was accompanied by higher pre- and postovulatory FSH levels, but there was no change in the pattern of circulating LH. Furthermore, the postovulatory FSH surge persisted for longer periods of time in the immunized than control animals. These results demonstrate the potency of the human recombinant alpha-subunit as an immunogen and illustrate its specificity in suppressing the effects of endogenous inhibin. The results also point to inhibin as an important regulatory factor in controlling the ovulation rate by modulating both pre- and postovulatory FSH levels. PMID- 2105202 TI - Inhibition of chondroitin sulfate incorporation into human thyroglobulin by p nitrophenyl-beta-D-xylopyranoside. AB - Human thyroglobulin (TG) is unique among glycoproteins and TGs of other species in having a chondroitin sulfate chain. We studied the effects of p-nitrophenol beta-D-xylopyranoside (PNXP), an inhibitor of chondroitin sulfate incorporation into core protein of proteoglycans, on the synthesis of human TG. Fragments of normal thyroid tissue from two patients were preincubated for 1 h with PNXP before adding [35S] sulfate and [3H]leucine. TG was purified by ammonium sulfate precipitation, sucrose gradient centrifugation, and CsCl equilibrium density gradient centrifugation. Chondroitin ABC lyase released 38-42% of the [35S]sulfate from control TG, synthesized in the absence of inhibitor, demonstrating the presence of chondroitin sulfate units. In the samples incubated with increasing concentrations of PNXP (0.2 and 1 mM), the fraction of [35S] sulfate released by ABC lyase decreased progressively (14-23% and 8-11%, respectively). This confirms that, as in chondroitin sulfate proteoglycans, chondroitin sulfate synthesis in TG is initiated by the transfer of a galactose unit, by galactosyltransferase, to a xylosyl-serine in the TG peptide backbone. This step is prevented by PNXP, which is a competitive acceptor of galactose. The density of TG synthesized in the presence of PNXP was determined by CsCl equilibrium density centrifugation. [3H] leucine-labeled TG from the samples incubated with PNXP was less dense than [3H]leucine-labeled TG from the control specimen. The newly synthesized TG was less dense either because of the lack of the chondroitin sulfate chain or because further processing of the TG was impaired. To differentiate these possibilities, we treated control, [3H]leucine labeled TG with chondroitin ABC lyase and compared its density to that of [3H] leucine-labeled TG synthesized in the presence of 1 mM PNXP. The decrease in density produced by PNXP was greater than the decrease brought about by chondroitin ABC lyase (4.3-5.2 x 10(-3) and 2.4-2.8 x 10(-3) g/cm3, respectively). Therefore, the density contributed by the chondroitin chain was insufficient to account for the entire density shift seen with PNXP. We conclude that 1) chondroitin sulfate synthesis is initiated by the transfer of a galactosyl unit to xylosyl-serine in the TG peptide backbone; and 2) inhibition of this step decreases the density of TG by preventing the addition of the chondroitin chain and interfering with the further processing of TG. PMID- 2105203 TI - Estrous cycle-related changes of high affinity luteinizing hormone/human chorionic gonadotropin binding sites in the rat uterus. AB - LH/human CG (LH/hCG) high affinity binding sites were detected in crude membrane preparations of rat uteri. There was little competition for receptor occupancy between hCG and ovine FSH (oFSH) (0.05%) and no competition between hCG and ovine PRL (less than 0.01%). No similar binding sites were detected in crude membrane preparation of heart, kidney, skeletal muscle, liver, and lung tissues. Concentrations of uterine unoccupied binding sites (RLH) were determined for each stage of the 4-day estrous cycle. The RLH were found in all preparations of metestrus uteri (n = 10) but only in some preparations from the other stages of the estrous cycle (1 of 7 on proestrus, 3 of 4 on estrus, 5 of 7 on diestrus). The concentration of uterine RLH varied throughout the estrous cycle with highest values during the metestrus (1.50 +/- 0.15 fmol/mg protein) and lowest values during the proestrus (less than 0.2 fmol/mg protein). The affinity constant for hCG of uterine RLH remained constant during the estrous cycle (about 0.8 x 10(11) M-1) and was nearly identical to that of rat ovarian receptors. On metestrus, RLH concentration appeared to be approximately 35-fold lower in the uterus than in the ovaries when expressed per mg protein (1.50 +/- 0.15 vs. 52.83 +/- 3.61 fmol/mg protein) but only 20 times lower when expressed per organ (2.2 vs. 48.3 fmol/organ). The estrous cycle-related changes of uterine RLH concentration, together with our data establishing an in vitro influence of hCG on progesterone metabolism in rat uterus, suggest that some uterine functions could be directly regulated either by LH from the pituitary or during early pregnancy by an LH-like substance originating from the embryo. PMID- 2105204 TI - In vivo pertussis toxin administration: effects on the function and levels of Gi alpha proteins and their messenger ribonucleic acids. AB - Pertussis toxin ADP-ribosylates and functionally inactivates a number of guanine nucleotide-binding proteins (G-proteins), including the inhibitory G-protein, Gi. Once ADP-ribosylated, the subsequent duration of inactivation and fate of these proteins in cells are unknown. In the present study, therefore, we have attempted to answer some of these questions in an in vivo rat adipocyte model. Our results indicate a rather prolonged (greater than 2 weeks) inactivation of Gi, as evidenced by loss of R-phenylisopropyladenosine-mediated inhibition of adenylate cyclase activity in rat adipocyte membranes after administration of the toxin in vivo. This was associated with a complete loss of pertussis toxin ADP ribosylatable substrates on days 3 and 15, with only partial recovery by day 28 after initiation of treatment. Specific antibodies used to quantitate the levels of alpha i1- and alpha 12-subunits of alpha i indicate a 2-fold increase in the levels of these proteins by day 3, followed by a progressive decrease and subsequent recovery in these subunits to 53%, 47%, and 87% of the control value on days 15, 20, and 28, respectively. No change in the levels of alpha s was observed at all time points tested. The levels of mRNA encoding the alpha i proteins were measured using specific oligonucleotide probes to determine whether changes in the levels of these transcripts could explain the observed regulation of alpha i. At the early time point (day 3), there was no alteration in the mRNA for alpha 3, alpha i1, alpha i2, and alpha i3 in fat pads from control and treated rats. However, the levels of the alpha i1 transcript decreased slightly in the treated groups on day 15-20 by a maximum of 33% and partially recovered by day 28. No changes in the alpha i2, alpha i3, alpha s, or tubulin transcripts were observed over the same treatment period. These results provide the first evidence that ADP ribosylation of the alpha i proteins by pertussis toxin leads to significant alterations in their levels. Furthermore, alterations in the levels of alpha i proteins (except alpha i1) do not appear to result from transcriptional regulation. PMID- 2105205 TI - Ovarian follicle-stimulating hormone binding changes associated with the reinstatement of ovulatory cycles after lactation interruption in the rat. AB - The aim of this work was to study the endocrine changes that occur during the reinstatement of the ovulatory cycles after lactational infertility in the rat. Hormonal patterns and specific binding of [125I]FSH to ovaries of lactating rats that kept their pups (LRP) or were separated from their pups on day 13 postpartum (LRX) were studied on days 13-16 postpartum. In LRP rats gonadotropin levels remained low and unvarying throughout the experiment; PRL levels were high in the morning, low at 1300 h, and then surged in the afternoon. Estradiol levels were very low in LRP rats in serum as well as in ovarian homogenates, and progesterone levels decreased gradually from days 13 to 16. No changes in either receptor number or dissociation constants (Kd) were observed in [125I]FSH binding to ovaries of LRP rats. In LRX rats, LH peaked on the afternoon of day 15 (P less than 0.05). FSH decreased from morning levels on day 13 to morning levels on day 15, and then peaked at 1600 h on day 15 (p less than 0.05). PRL decreased rapidly (day 13 1600 h levels significantly lower than day 13 1100 h levels), then remained low and peaked on the afternoon of day 15 (P less than 0.05). IN LRX rats progesterone levels decreased more markedly than in LRP rats and then surged in the afternoon of day 15. Serum estradiol levels rose significantly in the morning of day 15, while ovarian homogenate estradiol titers had already risen on the morning of day 14. Significant increases in number of [125I]FSH-binding sites and Kd values were observed in LRX rats on day 15 postpartum. These results clearly show that litter removal at midlactation (day 13) induces the reinstatement of hormonal cyclicity, and this is accompanied by changes in ovarian FSH receptors. PMID- 2105206 TI - Diminished bioactivity of circulating prolactin despite increased immunoreactive hormone release in old versus young male rats. AB - The Nb2 rat lymphoma PRL bioassay and standard RIA techniques were used to compare the impact of aging on immunoreactive (ir) and bioactive (bio) plasma PRL levels in 3- to 5- and 22- to 24-month-old male Copenhagen-Fischer rats. Basal plasma irPRL levels were significantly higher, while bioPRL were significantly lower in old compared to young rats. Administration of 10 mg/kg morphine similarly increased plasma irPRL levels in both age groups, but elevations in bioPRL were significantly lower in the older animals. Administration of 1 mg/kg haloperidol significantly increased circulating levels of ir- and bioPRL in both age groups, but these responses were significantly attenuated in the older rats. Treatment with 10 mg/kg bromocryptine resulted in significantly greater decreases in plasma irPRL levels in young rats, but induced similar decreases in bioPRL levels in both age groups. Administration of 25 micrograms/kg TRH induced similar increases in both ir- and bioPRL levels in young and old male rats. These results demonstrate that basal plasma bioPRL levels are significantly lower in old compared to young male rats, and specific drug treatments differentially alter the ratio of plasma bio- vs. irPRL levels in these age groups. These findings suggest that during the aging process not only quantitative changes but also qualitative changes occur in PRL secretion, which result in an overall decline in the biopotency of PRL released into the circulation. PMID- 2105207 TI - Acute effect of basic fibroblast growth factor on secretion of prolactin as assessed by the reverse hemolytic plaque assay. AB - The effect of basic fibroblast growth factor (bFGF) on acute secretion of PRL by pituitary lactotrophs was examined under basal conditions and after treatment with TRH or dopamine. We used the reverse hemolytic plaque assay (RHPA) to determine the amount of PRL secreted per lactotroph and the percentage of pituitary cells secreting PRL. Young (2- to 3-month-old) female Sprague-Dawley rats were ovariectomized and 1 week later implanted with a Silastic capsule containing 180 micrograms/ml estradiol in sesame oil. Three days later, rats were killed, anterior pituitaries were removed, and cells were enzymatically dispersed and prepared for use in the RHPA. In Exp I, time and dose responses to bFGF were determined using the RHPA. Basic FGF reduced (P less than 0.0001) the mean basal secretion of prolactin per lactotroph. The effect was similar at 30, 60, 120, and 240 min of incubation. The reduction in PRL was greatest at 3.36 x 10(-6) M, while lesser reductions were observed at 1.68 x 10(-6) and 5.60 x 10(-7) M. A dose of 3.36 x 10(-6) M (60 ng/ml) and an incubation time of 60 min were subsequently used in Exp II. In Exp II, we examined the effects of bFGF on TRH stimulation and dopamine inhibition of PRL secretion. PRL secretion was maximally stimulated (P less than 0.01) by 10(-7) M TRH. Basic FGF blocked the TRH-induced increase in PRL secretion. PRL secretion was maximally reduced (P less than 0.001) by 10(-5) M dopamine. Coincubation of bFGF with dopamine reduced (P less than 0.01) the mean plaque area to the same extent as dopamine alone. In each experimental situation changes in mean plaque area reflected a shift in the frequency distribution of the plaque area. Neither bFGF, TRH, dopamine, nor the combined treatments influenced the percentage of pituitary cells secreting PRL compared to basal conditions. We have demonstrated that 1) bFGF reduces the basal secretion of PRL in an acute manner; 2) bFGF blocks the TRH-induced increase in PRL; and 3) bFGF does not potentiate the inhibitory effect of dopamine on PRL secretion and, therefore, may act in part through the same inhibitory pathway as dopamine. We conclude from these data that bFGF, or related factors, could play a role in the regulation of PRL secretion. PMID- 2105208 TI - Enhancement of thyroxine entry into low density lipoprotein (LDL) receptor competent fibroblasts by LDL: an additional mode of entry of thyroxine into cells. AB - Having demonstrated that plasma low density lipoproteins (LDL) bind T4 through a specific interaction with their sole apolipoprotein, apoB-100, we tested the hypothesis that cells could internalize the LDL-T4 complex via cell surface LDL receptors. These receptors are down-regulated by cholesterol loading and up regulated by cholesterol deficiency. We, therefore, studied the uptake of [125I]T4 or [125I]T3 by human skin fibroblasts grown in 10% lipoprotein-deficient serum in the absence or presence of LDL. At concentrations of LDL (12.5 and 22 micrograms protein/ml) that gave significant binding of T4 but did not exceed LDL receptor capacity, both the initial rate of saturable T4 uptake and the uptake at equilibrium increased by 27-63%. No significant increase occurred at a LDL concentration of 1.6 micrograms protein/ml (less than 3% occupancy), whereas there was a 20 to 31% reduction at 125 micrograms/ml (approximately 5 times the saturation dose for the LDL receptor). These changes were confirmed with several different LDL preparations and were mimicked by isolated apoB-100 and apoE, the sole ligands for the LDL receptors (apoB/E receptors). T4 uptake did not increase in normal fibroblasts with down-regulated LDL receptors or in LDL receptor deficient fibroblasts from a patient with familial hypercholesterolemia. In the latter cell line the uptake of T4 (and T3) in the absence of LDL was indistinguishable from that of normal fibroblasts. T3 uptake in normal fibroblasts was not enhanced by LDL. The specificity of the LDL effect was shown by the finding that T4-binding globulin, prealbumin, or serum albumin, at concentrations giving 10-90% T4 bound, failed to increase T4 uptake. Instead, each of these major thyroid hormone-binding plasma proteins caused a dose dependent decrease in T4 entry. It is concluded that at least two modes of entry into fibroblasts are available for T4. The first is the cell surface thyroid hormone-binding sites, which recognize the free hormone and are present in both normal and LDL receptor-negative fibroblasts. The second, and additional, mode of entry is via the LDL receptors, which recognize the T4-LDL complex, are absent in LDL receptor-negative fibroblasts, are reduced in down-regulated fibroblasts, and are unavailable for T3, owing to the low affinity of T3 for LDL. PMID- 2105209 TI - Luteinizing hormone (LH)-releasing hormone: chronic effects on LH and follicle stimulating hormone cells and secretion in adult male rats. AB - We investigated whether chronic administration of LHRH to normal adult rats could increase the percentages of anterior pituitary gland (APG) cells that contain immunoreactive LH and/or FSH and gonadotropin secretion. Vehicle or 1 microgram LHRH was injected sc twice daily for 6 days, and rats were decapitated 16 h after the last injection. Treatment with LHRH caused nearly a doubling in the numerical density of LH and FSH cells and in the percentage of APG cells that contained LH or FSH. It also caused a shift in the gonadotroph population from LH and LH/FSH cells to LH/FSH cells. It did not change the mean size of gonadotrophs or APG weight. These changes at the light microscopic level were not accompanied by any apparent changes in LH cells at the ultrastructural level. However, they were accompanied by an approximate doubling of the basal serum LH and FSH concentrations, an increase in the APG FSH concentration, and an increase in the basal FSH release rate (measured in vitro). The results indicate that exogenous LHRH can be administered to increase numbers of gonadotrophs in the APG, synthesis of FSH in gonadotrophs, and basal serum LH and FSH concentrations. PMID- 2105210 TI - Relationships of total protein, specific gravity, viscosity, refractive index and latex agglutination to immunoglobulin G concentration in mare colostrum. AB - A colostrum sample was collected within 24 h after foaling from 27 mares and from 10 other mares a milk sample was collected several weeks post partum. Immunoglobulin G concentrations were determined quantitatively by radial immunodiffusion and semi-quantitatively using a commercial latex agglutination test. Total protein, specific gravity, viscosity and refractive index were determined and their relationships to the immunoglobulin G concentration analysed. All parameters correlated with the immunoglobulin G concentration. The latex agglutination test divided the colostrum samples into three groups with different means for immunoglobulin G and total protein concentrations. Specific gravity and the latex agglutination test were found to be the methods best suited for on-farm evaluation of colostrum quality. PMID- 2105211 TI - Interaction in situ of the cytoskeletal protein vinculin with bilayers studied by introducing a photoactivatable fatty acid into living chicken embryo fibroblasts. AB - The cytoskeletal protein vinculin, a putative actin--plasma-membrane linker, has been shown by hydrophobic photo-labeling to interact in vitro directly with bilayers of acidic phospholipids [Niggli et al. (1986) J. Biol. Chem. 261, 6912 6918]. In order to demonstrate that such an interaction occurs also in intact cells, chicken embryo fibroblasts were incubated for 2 h with a 3H-labeled photoactivatable fatty acid, 11-(4-[3-(trifluoromethyl)-diazirinyl]phenyl)-[2 3H]undecanoic acid. This resulted in biosynthetic incorporation into cellular lipids of a fraction of the fatty acid added. Following photolysis, vinculin was immunoprecipitated from different subcellular fractions using a specific polyclonal anti-vinculin antibody. The protein was recovered from both the cytosolic and the crude membrane fraction. Vinculin from both fractions incorporated label, but the membrane-associated population was at least eight times more strongly photolabeled than the cytosolic protein. Moreover, photolysis increased only labeling of the membrane-bound but not of the cytosolic protein. These results suggest that the direct interaction of vinculin with the hydrophobic core of the phospholipid layer observed in vitro may also be relevant in intact cells, and may be involved in its function as a linker protein. PMID- 2105212 TI - Resonance energy transfer between points in a reconstituted skeletal muscle thin filament. A conformational change of the thin filament in response to a change in Ca2+ concentration. AB - The spatial relationships between Lys-61, Cys-374 on actin or SH1 on myosin subfragment-1 (S1) and Cys-190 on tropomyosin or Cys-133 on troponin-I (TnI) in a reconstituted thin filament were studied by fluorescence resonance energy transfer. 5-(2-Iodoacetylaminoethyl)aminonaphthalene 1-sulfonic acid (IAEDANS) attached to Lys-190 on tropomyosin or to Cys-133 on TnI was used as a donor. Fluorescein 5-isothiocyanate (FITC) attached to Lys-61 or 5 (iodoacetoamido)fluorescein (IAF) attached to Cys-374 on actin and 4 dimethylaminophenyl-azophenyl 4'-maleimide (DABMI) attached to SH1 on S1 were used as an acceptor. The transfer efficiency between AEDANS attached to Cys-190 on tropomyosin and FITC attached to Lys-61 on actin was 0.42 in the absence of troponin, 0.46 in the presence of troponin and Ca2+ and 0.55 in the presence of troponin and absence of Ca2+. The corresponding distances between the probes were calculated to be 4.7 nm, 4.6 nm and 4.3 nm respectively, assuming a random orientation factor K2 = 2/3. A large difference in the transfer efficiency from AEDANS attached to Cys-133 on TnI to FITC attached to Lys-61 on actin was observed between in the presence (0.52) and absence (0.70) of Ca2+. The corresponding distances between the probes were calculated to be 4.5 nm in the presence of Ca2+ and 3.9 nm in the absence of Ca2+. The distance between Cys-190 on tropomyosin and Cys-374 on actin was measured to be 5.1 nm and the transfer efficiency (0.35) did not change upon addition of troponin whether Ca2+ is present or not, in agreement with the previous report [Tao, T., Lamkin, M. & Lehrer, S. S. (1983) Biochemistry 22, 3059-3064]. The distance between Cys-133 on TnI and Cys-374 on actin was measured to be 4.4 nm. No detectable change in transfer efficiency (0.58) was observed between values in the presence and absence of Ca2+. These results suggest that a relative movement of the two domains of actin monomer in a reconstituted thin filament occurs in response to a change in Ca2+ concentration. The transfer efficiencies between DABMI attached to SH1 on S1 and AEDANS attached to Cys-190 on tropomyosin or Cys-133 on TnI were too small (less than 2%) for an accurate estimation of the distances, suggesting the distances are longer than 7.3 nm. PMID- 2105214 TI - Arginyl groups involved in the binding of Anabaena ferredoxin--NADP+ reductase to NADP+ and to ferredoxin. AB - Chemical modification of ferredoxin--NADP+ reductase from the cyanobacteria Anabaena has been performed using the alpha-dicarbonyl reagent phenylglyoxal. Inactivation of both the diaphorase and cytochrome-c reductase activities, characteristic of the enzyme, indicates the involvement of one or more arginyl residues in the catalytic process of the enzyme. The determination of the rate constants for the inactivation process under different conditions, including those in which substrates, NADP+ and ferredoxin, as well as other NADP+ analogs were present, indicates the involvement of two different groups in the inactivation process, one that reacts very rapidly with the reagent (kobs = 8.3 M 1 min-1) and is responsible for the binding of NADP+, and a second less reactive group (kobs = 0.9 M-1 min-1), that is involved in the binding of ferredoxin. Radioactive labeling of the enzyme with [14C]phenylglyoxal confirms that two groups are modified while amino acid analysis of the modified protein indicates that the modified groups are arginine residues. The identification of the amino acid residues involved in binding and catalysis of the substrates of ferredoxin- NADP+ reductase will help to elucidate the mechanism of the reaction catalyzed by this important enzyme. PMID- 2105213 TI - Primary stimuli of icosanoid release inhibit arachidonoyl-CoA synthetase and lysophospholipid acyltransferase. Mechanism of action of hydrogen peroxide and methyl mercury in platelets. AB - Icosanoid formation in platelets depends on the concentration of free arachidonate that is mainly liberated from membrane phospholipids by phospholipase A2. The concentration of free arachidonate is also controlled by the activities of the reacylating enzymes arachidonoyl-CoA synthetase and lysophospholipid acyltransferase. In human platelet microsomes we determined the high enzyme activities of 5.9 nmol.min-1.(10(9) platelets)-1 for the arachidonoyl CoA synthetase and 37 nmol.min-1.(10(9) platelets)-1 for the lysophospholipid acyltransferase. The activities of these reacylating enzymes were strongly reduced by hydrogen peroxide (H2O2) and methyl mercury that are primary stimuli of arachidonate release in intact platelets. H2O2 inhibited the arachidonoyl-CoA synthetase with an IC50 of 3.3 mmol/l without affecting the lysophospholipid acyltransferase. Sulfhydryl group protection by 3-mercapto-1,2-propanediol did not overcome the inhibition but glutathione prevented the inhibition of the arachidonoyl-CoA synthetase by H2O2. This suggests that glutathione by virtue of the glutathione peroxidase reduces H2O2 rather than that it protects free sulfhydryl groups of the arachidonoyl-CoA synthetase. Methyl mercury left the arachidonoyl-CoA synthetase activity unaffected but inhibited the lysophospholipid acyltransferase activity with an IC50 of 3.4 mumol/l. The inhibition is probably evoked by the blockade of sulfhydryl groups of the lysophospholipid acyltransferase because it disappeared when 3-mercapto-1,2 propanediol was added at a concentration higher than that of methyl mercury. Thrombin as a physiological full agonist, Ca2+ less than or equal to 1 mmol/l, the calcium ionophore A23187 and phorbol 12-myristate 13-acetate (TPA) and 1 oleoyl-2-acetylglycerol as model stimuli of protein kinase C neither influenced arachidonoyl-CoA synthetase nor lysophospholipid acyltransferase. It is concluded that the inhibitory effect of H2O2 and methyl mercury on the arachidonate reacylating enzymes arachidonoyl-CoA synthetase or lysophospholipid acyltransferase, respectively, are responsible for their capacity to stimulate icosanoid release in intact cells. Thrombin and its intracellular messengers Ca2+ and diacylglycerol do not directly affect arachidonoyl-CoA synthetase and lysophospholipid acyltransferase. PMID- 2105215 TI - Ribofuranosyl-benzimidazole derivatives as inhibitors of casein kinase-2 and casein kinase-1. AB - 5,6-Dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DiCl-RB) is a powerful inhibitor of casein kinase-2 (CK-2) [Zandomeni, R. et al. (1986) J. Biol. Chem. 261, 3414-3420]. Here a series of 17 analogues of DiCl-RB has been employed for studying the specificity and the mode of action of this family of CK-2 inhibitors. The two halogen substituents on the benzene ring are shown to play a prominent role in inhibition, the 5,6-dibromo derivative (DiBr-RB) being fivefold more effective than DiCl-RB (Ki = 2 microM, with GTP as substrate), whereas the difluoro derivative (DiF-RB) is nearly as ineffective as unsubstituted 1-(beta-D ribofuranosyl)benzimidazole. On the other hand, although some modifications of the ribose group significantly decrease the inhibitory efficiency, the sugar moiety is not strictly required, since dichlorobenzimidazole itself (DiCl-Bz) is an inhibitor almost as good as DiCl-RB. Inhibition of CK-2 by DiCl-RB and by its analogues, DiCl-Bz included, is of the competitive type with respect to the nucleotide substrate, the Ki values being lower with GTP than with ATP. The Ki values of the most potent inhibitor, DiBr-RB, with ATP and GTP, are 6 microM and 2 microM, respectively, denoting an affinity for the enzyme higher than that of the physiological substrates, ATP and GTP. DiBr-RB has been assayed for its inhibitory capacity toward several protein kinase other than CK-2. Protein kinase C, cAMP-dependent protein kinase, the Ser/Thr protein kinase expressed by Pseudorabies virus, and four different tyrosine protein kinases from spleen, proved insensitive to DiBr-RB concentrations capable of almost entirely suppressing the activity of rat liver and maize seedling CK-2. Casein kinase-1 however is nearly as sensitive as CK-2 to DiBr-RB. Inhibition of CK-1 is also of the competitive type with respect to ATP (Ki = 14 microM). Although the inhibitory spectrum of CK-1 by the various analogues is reminiscent of that observed with CK-2, a remarkable difference is revealed by 5'-phosphorylation of ribose which increases the Ki with CK-2 while decreasing that with CK-1. PMID- 2105216 TI - Thermostable beta-galactosidase from the archaebacterium Sulfolobus solfataricus. Purification and properties. AB - A thermophilic and thermostable beta-galactosidase activity was purified to homogeneity from crude extracts of the archaebacterium Sulfolobus solfataricus, by a procedure including ion-exchange and affinity chromatography. The homogeneous enzyme had a specific activity of 116.4 units/mg at 75 degrees C with o-nitrophenyl beta-galactopyranoside as substrate. Molecular mass studies demonstrated that the S. solfataricus beta-galactosidase was a tetramer of 240 +/ 8 kDa composed of similar or identical subunits. Comparison of the amino acid composition of beta-galactosidase from S. solfataricus with that from Escherichia coli revealed a lower cysteine content and a lower Arg/Lys ratio in the thermophilic enzyme. A rabbit serum, raised against the homogeneous enzyme did not cross-react with beta-galactosidase from E. coli. The enzyme, characterized for its reaction requirements and kinetic properties, showed a thermostability and thermophilicity notably greater than those reported for beta-galactosidases from other mesophilic and thermophilic sources. PMID- 2105217 TI - Aspartate aminotransferase with the pyridoxal-5'-phosphate-binding lysine residue replaced by histidine retains partial catalytic competence. AB - The active site residue lysine 258 of chicken mitochondrial aspartate aminotransferase was replaced with a histidine residue by means of site-directed mutagenesis. The mutant protein was expressed in Escherichia coli and purified to homogeneity. Addition of 2-oxoglutarate to its pyridoxamine form changed the coenzyme absorption spectrum (lambda max = 330 nm) to that of the pyridoxal form (lambda max = 330/392 nm). The rate of this half-reaction of transamination (kcat = 4.0 x 10(-4)s-1) is five orders of magnitude slower than that of the wild-type enzyme. However, the reverse half-reaction, initiated by addition of aspartate or glutamate to the pyridoxal form of the mutant enzyme, is only three orders of magnitude slower than that of the wild-type enzyme, kmax of the observable rate limiting elementary step, i.e. the conversion of the external aldimine to the pyridoxamine form, being 7.0 x 10(-2)s-1. Aspartate aminotransferase (Lys258--- His) thus represents a pyridoxal-5'-phosphate-dependent enzyme with significant catalytic competence without an active site lysine residue. Apparently, covalent binding of the coenzyme, i.e. the internal aldimine linkage, is not essential for the enzymic transamination reaction, and a histidine residue can to some extent substitute for lysine 258 which is assumed to act as proton donor/acceptor in the aldimine-ketimine tautomerization. PMID- 2105218 TI - Effect of the N-terminal hydrophobic sequence of hepatitis B virus surface antigen on the folding and assembly of hybrid beta-galactosidase in Escherichia coli. AB - To investigate the mechanism of inclusion body formation and the effect of a hydrophobic sequence on the in vivo polypeptide folding, the aggregation caused by recombinant fusion beta-galactosidase in Escherichia coli was examined. Two plasmids were constructed: pTBG(H-) carried only the preS2 sequence of the hepatitis B virus surface antigen (HBsAg) in front of the beta-galactosidase gene (lacZ) while pTBG(H+) carried an additional sequence encoding the amino-terminal hydrophobic sequence of the S region of HBsAg between preS2 and lacZ. Unlike cells expressing the fusion protein not containing the hydrophobic sequence, E. coli JM109/pTBG(H+) exhibited temperature-sensitive production of beta galactosidase. As the culture temperature increased the activity decreased dramatically. This decrease in activity was not due to a decrease in fusion polypeptide production, but rather the fusion polypeptides containing the hydrophobic sequence aggregated within the cells at high temperature. However once the fusion polypeptides folded into proper conformation at low temperature, they maintained the activity even at high temperature. The results indicate that aggregation is a consequence of incorrect folding and assembly of the polypeptides, and is not derived from the native structure. The aggregates of the pTBG(H+)-encoded fusion polypeptides did not revert to active form when the culture temperature was lowered. PMID- 2105219 TI - Characterisation of a monoclonal antibody against native human type I collagen. AB - A monoclonal antibody against a pepsin-soluble mammalian type I collagen has been produced. This antibody, subclass IgG1, kappa, was specific for type I collagen and did not cross-react with a range of other collagen types or connective tissue proteins. The epitope recognized by the antibody was dependent upon an intact triple-helical structure for the collagen, and was shown by rotary shadowing and by immunoblotting of collagenase-derived fragments to be near the C-terminal of the pepsin-soluble collagen. Although the antibody had a low affinity, with Kd = 4 x 10(-7) M, it could be used for immunohistology of tissue sections and for studies of collagen produced by cells in culture. The antibody, which was raised against human collagen, also recognized type I collagens from certain other species, including calf, pig, sheep, goat and dog. PMID- 2105220 TI - Cytostatic factor (CSF) activity in cytosols extracted from Xenopus laevis eggs. AB - Cytostatic factor (CSF), found in the cytoplasm of unfertilized eggs of amphibians, causes metaphase arrest when microinjected into cleaving blastomeres. Although CSF from Rana pipiens eggs has been extracted and characterized, little is known about CSF extracted from eggs of other species. We investigated the conditions required to preserve CSF activity in cytosols extracted from Xenopus laevis eggs and found that it was necessary to expose the eggs to CO2 prior to extraction and that the extraction buffer must contain sodium beta glycerophosphate. CSF activity disappeared after 24 h of storage at 2 degrees C. Cytological examination showed that the arrested blastomeres injected with cytosols had been arrested at metaphase and contained a spindle lacking polar asters, in which highly condensed chromosomes were embedded. PMID- 2105222 TI - Binding of nuclear factors to the 5'-interferon consensus sequence of the HLA-A2 class I gene. AB - To investigate the regulatory role of the conserved interferon consensus sequence (ICS) found in the 5' flanking region of HLA class I genes, we studied the binding of nuclear proteins to the ICS of HLA-A2 gene (ICS-A2) by the gel shift assay. Nuclear extracts from several human cell lines expressing different levels of surface class I molecules reveal an ICS-A2-protein complex of similar mobility, the amount of which varies in a cell type-dependent manner. In some cell lines, interferon-gamma treatment decreased the level of this complex. The overlapping enhancer A element also competes for the formation of this ICS-A2 protein complex. Footprinting and methylation interference analyses demonstrate that nuclear protein(s) protect specific sequences within the ICS-A2 element, suggesting that these protein(s) may represent interferon-sensitive transcription factors. PMID- 2105221 TI - Association of cytoskeletal proteins with newly formed acetylcholine receptor aggregates induced by embryonic brain extract. AB - Aggregates of acetylcholine receptors (AChR) in muscle cell membranes are associated with accumulations of certain cytoskeletal and peripheral membrane proteins. We treated cultured rat myotubes briefly with embryonic brain extract (EBX) to promote AChR aggregation and determined the distribution of several of these proteins at early stages of aggregation. EBX-treated and control cultures were stained with tetramethylrhodamine-alpha-bungarotoxin to identify AChR aggregates and were then frozen and sectioned on a cryostat. These sections were stained with primary antibodies and fluoresceinated secondary antibodies to localize cytoskeletal proteins. The distributions of AChRs and cytoskeletal proteins was examined qualitatively and analyzed by a semiquantitative assay. Qualitatively, the 43K protein had a distribution that was virtually identical to that of AChR in both control and EBX-treated cultures, and it always colocalized with early AChR aggregates. The 58K protein similarly colocalized with early AChR aggregates, but it was also in aggregate-free areas of muscle membrane. The association of vinculin with the aggregates was quantitatively similar to that of the 43K and 58K proteins, but, qualitatively, its distribution did not follow that of the AChR as closely. Like the 58K protein and vinculin, alpha-actinin, filamin, and actin were concentrated in AChR aggregates and were also enriched elsewhere. However, they were less closely associated with the aggregates, both quantitatively and qualitatively. These results show that AChR aggregates induced by EBX tend to be enriched in the same cytoskeletal proteins that are present at the neuromuscular junction in vivo and at AChR clusters formed at sites of cell substrate adhesion in vitro. Semiquantitative analysis also revealed that the fractional area of the cell surface associated with vinculin, alpha-actinin, and the 58K protein was the same in controls and EBX-treated myotubes, although the area enriched in AChR and the 43K protein increased about three-fold upon EBX treatment. These results suggest that AChR aggregates may form preferentially in membrane regions that are already enriched in these proteins. PMID- 2105223 TI - Actin cytoskeleton of resting bovine platelets. AB - Actin filaments in resting discoid bovine platelets were examined by fluorescence and electron microscopy. Rhodamine-phalloidin staining patterns showed a characteristic wheel-like structure which consisted of a central small circle connected by several radial spokes to a large peripheral circle. This wheel-like structure was composed of actin filaments forming a characteristic arrowhead structure with heavy meromyosin from muscle. Actin filaments were densely arrayed in parallel with a marginal microtubule band and radiated out from the center to the periphery. Platelets treated with colchicine lost their marginal microtubule band but retained their wheel-like structure and normal discoid form. Cytochalasin B disrupted the wheel-like structure but not the marginal microtubule band or the normal discoid form. After simultaneous treatment with both cytochalasin B and colchicine, platelets lost their discoid shape. These results suggest that actin filaments and microtubules both play important roles in the maintenance of the discoid shape of resting bovine platelets. PMID- 2105224 TI - c-fos and c-myc expression in human endothelial cells as a function of different culture conditions. AB - Cultured human umbilical vein endothelial cells (HEC) could be induced to express c-fos and c-myc mRNA by either serum or ECGS (endothelial cell growth supplement). Neither agonist separately could support HEC proliferation but the combination did. Expression of c-fos and c-myc mRNA in the presence of both serum and ECGS was similar to that observed after each of the two stimuli was introduced separately. c-fos and c-myc expression in cultured HEC, even if related, is not necessarily accompanied by stimulation of cell growth. PMID- 2105225 TI - Urokinase and tissue type plasminogen activators in human keratinocyte culture. AB - Using immunocytochemical and biochemical techniques, we have demonstrated that cultured human epidermal keratinocytes contain both urokinase and tissue type plasminogen activators. In subconfluent colonies the distribution of the two enzymes differed. Tissue type plasminogen activator (tPA) was distributed evenly throughout the colony, while, as we have demonstrated previously, urokinase type plasminogen activator (uPA) was preferentially localized at the migrating edges of the colony. Using zymographic analyses, both tPA and uPA activities were detected in cell extracts. Depending on the procedure used to prepare cell extracts, tPA was detected either as free enzyme or in complex with PA inhibitor type 1. PA inhibitor type 1 was deposited onto the extracellular matrix of the keratinocyte cultures and formed a complex with cell-associated tPA when cells and matrix were extracted together. The most differentiated keratinocytes in the culture, which were spontaneously shed from the culture surface, also contained both tPA and uPA. However, these spontaneously shed cells had a higher ratio of tPA:uPA than did the less differentiated cells from the same culture. In conjunction with our previous studies, these results demonstrate the complex nature of the plasminogen activator system, including enzymes and inhibitors, that is present in human keratinocytes. In addition, our data suggest that the relative amounts of uPA and tPA in epidermal cells vary with differentiation state. PMID- 2105226 TI - Relationship between intracellular pH (pHi) and calcium (Cai2+) in avian heart fibroblasts. AB - Measurements of pHi and Cai2+ were made in single isolated avian heart fibroblasts using the fluorescent dyes 2,3-dicyanohydroquinone (DCH) and Indo-1. The resting level of Cai2+ is in part maintained by an influx of Ca2+ from the external medium. This flux was reduced in the absence of Ca0(2+) or by adding 2 mM LaCl3 or CoCl2 to the bathing medium; however, it was insensitive to calcium channel blockers nifedipine and verapamil. BAPTA (25 microM), a calcium chelator, also reduced Cai2+. Changes in Cai2+ brought about by any of these methods were found to be accompanied by an intracellular acidification. Experiments were carried out altering pHi using trimethylamine, propionate, and ammonium chloride to determine whether pHi could influence Cai2+. It was found that an intracellular acidification induced a fall in Cai2+ and any rise in pHi induced a rise in Cai2+. These results suggest a direct interaction between Cai2+ and pHi. Various models are described which may account for the experimental observations. The findings are discussed in terms of the possible roles for pHi and Cai2+ and their interactions to influence cell motility and adhesion. PMID- 2105227 TI - Increase in histone poly (ADP-ribosylation) in mitogen-activated lymphoid cells. AB - Poly (ADP-ribosylated) histones appear to be intermediates in nuclear processes that involve DNA strand breaks. We have studied histone ADP-ribosylation in cellular lysates from activated human lymphoid cells in culture. Modified histones differing in the number of ADP-ribose groups gave separate bands upon two-dimensional gel electrophoresis. Cellular lysates from control cells contained histones modified with 1 to 15 ADP-ribose groups. Stimulation of the cells during culture with phytohemagglutinin (PHA) or a phorbol ester (TPA) as well as combinations of these two reagents led to a significant increase in the upper limit number of ADP-ribose groups attached to histones in the presence of divalent metal ions. Hyper (ADP-ribosylated) H2B carrying at least 32 ADP-ribose groups gave a distinctly characteristic pattern on two-dimensional gels showing that highly ordered enzymatic steps are followed for its synthesis. Moreover, it was found that PHA and/or TPA induces branching of the poly (ADP-ribose) on H2B. The increase in histone poly (ADP-ribosylation) following lymphocyte activation was less dramatic during incubation of cellular lysates in the absence of divalent metal ions. The increased histone modification observed in this study may result from an increase in cell proliferation during activation of lymphoid cells. The finding that the number of ADP-ribose groups on H4 equals or exceeds by one the number of acetyl groups suggests that the two modifications may share common functions. PMID- 2105228 TI - Cluster formation of canine dendritic cells and lymphocytes is calcium dependent and not inhibited by cyclosporine. AB - Canine peripheral blood mononuclear cells (PBMC), dendritic cells (DC), and lymphocytes either alone or in combination were cultured with concanavalin A (ConA), calcium ionophore, and phorobol-12-myristate-13-acetate (PMA), and examined for lymphocyte/DC cluster formation and lymphocyte proliferation as determined by thymidine uptake. ConA- or calcium ionophore-stimulated proliferation of PBMC required the presence of normal DC, and was preceded by cluster formation of DC and lymphocytes. PMA-triggered proliferation was not preceded by cluster formation but also required the presence of normal DC. The presence of ultraviolet (UV)-irradiated rather than normal DC did not permit ConA , calcium ionophore-, or PMA-triggered lymphocyte proliferation. Addition of interleukin 2 (IL-2) to cultures of lymphocytes and UV-irradiated DC restored responsiveness to PMA, suggesting that a decrease in cytokine production was the central event in UV-induced accessory cell inhibition. Cyclosporine, known to interfere with IL-2 release and responses, completely blocked both ConA- and PMA induced lymphocyte proliferation but did not interfere with ConA-triggered cluster formation. Verapamil blocked both cluster formation and proliferation. These data show that DC/lymphocyte cluster formation is Ca2+ dependent and cannot be inhibited by cyclosporine. The data show, furthermore, that in agreement with findings in other species, triggering of canine lymphocytes by lectins and phorbol esters follows distinct pathways. PMID- 2105229 TI - Trypanosoma cruzi: maintenance of parasite-specific T cell responses in lymph nodes during the acute phase of the infection. AB - Mice infected with 5 x 10(3) forms of Trypanosoma cruzi showed a transient, but severe impairment of in vitro spleen cell responses to parasite antigens and to Concanavalin A (Con A). In contrast, inguinal and periaortic lymph node (LN) cells displayed high parasite-specific proliferative responses and only a partial reduction of the Con A-induced proliferation during the acute and chronic phases of infection. Lymphocytes that underwent blastic transformation in T. cruzi stimulated cell cultures were of the L3T4+ phenotype. Suppression of spleen cell responses occurred in the acute phase whether mice were infected with high (3 x 10(5] or low (5 x 10(3] doses of T. cruzi by intraperitoneal or subcutaneous route. Suppression of the T. cruzi-specific proliferative response of LN cells was only observed in mice infected with high subcutaneous inocula. This suppression, however, was restricted to the LNs draining the site of inoculation without affecting distant LNs. Supernatants from parasite-stimulated proliferating LN cells displayed low or undetectable T cell growth factor (TCGF) activity, in contrast with the high TCGF levels found in supernatants of the same cells stimulated with Con A. Low levels of TCGF were also detected in cultures of LN cells from mice immunized with T. cruzi extracts. Neither the T. cruzi antigen used for in vitro stimulation nor the LN cell supernatants from infected mice inhibited TCGF activity. These findings indicate that (1) parasite-specific responses are present in the LN compartment throughout the acute phase of T. cruzi infection in mice and (2) the proliferative response of L3T4+ LN cells from infected mice to T. cruzi antigens is not associated with a high TCGF secretory response. PMID- 2105230 TI - Trypanosoma cruzi: quantification in tissues of experimentally infected mice by limiting dilution analysis. AB - A limiting dilution assay (LDA) was developed for the quantification of Trypanosoma cruzi in the heart and blood of infected mice. Three groups of swiss mice were injected ip with "CL", "Colombiana," and "Y" strains. At 1-day intervals after infection, blood and the heart were removed. Serial blood dilutions in LIT medium were performed and distributed in four groups of 24 microplate wells. The growth of parasite was visually checked in an inverted microscope. It was found that curves of parasitemia obtained by parasite counting in a hemocytometer or estimated by LDA were similar. A similar method was used to quantify parasites in the heart of mice. The heart was cut, washed, dried, and its weight was determined. The heart pieces were disrupted by passage through a mesh stainless-steel screen into LIT. Serial dilutions of the heart homogenate were made in LIT and added to at least 24 replicate microplate wells. Parasites were detectable earlier in the heart of mouse infected with Y strain when compared to CL and Colombiana strains. Parasites were detected in the heart of mice of all strains by 6 days after infection. This LDA for quantification of T. cruzi permits a more precise evaluation of the number of living parasites in infected tissues. PMID- 2105231 TI - The hatching of schistosome eggs. PMID- 2105232 TI - Asp83, Glu113 and Glu134 are not specifically involved in Schiff base protonation or wavelength regulation in bovine rhodopsin. AB - Site-specific mutagenesis was employed to investigate the proposed contribution of proton-donating residues (Glu, Asp) in the membrane domains of bovine rhodopsin to protonation of the Schiff base-linking protein and chromophore or to wavelength modulation of this visual pigment. Three point-mutations were introduced to replace the highly conserved residues Asp83 by Asn (D83N), Glu113 by Gln (E113 Q) or Glu134 by Asp (E134D), respectively. All 3 substitutions had only marginal effects on the spectral properties of the final pigment (less than or equal to 3 nm blue-shift relative to native rhodopsin). Hence, none of these residues by itself is specifically involved in Schiff base protonation or wavelength modulation of bovine rhodopsin. PMID- 2105233 TI - The psbC start codon in Synechocystis sp. PCC 6803. AB - The translation start codon for psbC, the gene encoding CP43, a chlorophyll binding protein of photosystem II, has been identified for the cyanobacterium Synechosystis sp. PCC 6803 using site-directed mutagenesis. An AUG codon, about 50 bases upstream from the end of psbD-I had previously been assumed to be the translation start site of psbC. However, the fact that the AUG codon is not present in psbC from several other organisms, whereas a GUG codon 14 bases upstream from the end of psbD-I is strictly conserved suggests that CP43 translation starts at the latter codon. Mutation of GUG, but not of AUG, led to a loss of CP43 and photoautotrophic growth, indicating that the GUG codon is the sole initiation site for translation of the CP43 protein in Synechocystis sp. PCC 6803. PMID- 2105234 TI - Feedback regulation of ornithine decarboxylase expression. Studies using a polysomal run-off system. AB - The rate-controlling enzyme in polyamine synthesis, ornithine decarboxylase (ODC), is subject to feedback regulation by the polyamines at the level of translation. In the present study we used a cell-free translation system to further investigate the mechanism by which this regulation occurs. Lysates of ODC overproducing cells were capable of synthesizing large amounts of ODC. The degree of initiation was poor in the lysates and the synthesis of ODC was mainly a result of continued elongation of peptide chains on pre-initiated ribosomes. By determining the amount of ODC produced in the lysate, we obtained an estimate of the number of ribosomes that were actively translating ODC mRNA at the moment of lysis. Using this polysomal run-off assay we demonstrated that the polyamine mediated regulation of ODC synthesis occurs without any change in the number of ribosomes associated with the message. This finding indicates that the polyamines exert a coordinate effect on initiation and elongation. PMID- 2105235 TI - Identification of multiple ral gene products in human platelets that account for some but not all of the platelet Gn-proteins. AB - Polyclonal antibodies raised against specific recombinant low molecular mass GTP binding proteins were tested for their ability to recognize partially purified human platelet membrane Gn-proteins (i.e. proteins that bind [alpha-32P]GTP on nitrocellulose blots of SDS/polyacrylamide gels). An antiserum against simian ralA protein recognized a 27 kDa human platelet protein with the same apparent molecular mass as the major platelet Gn-protein (Gn27). In further analysis by two-dimensional polyacrylamide gel electrophoresis, the isoelectric focusing step permitted resolution of 12 major Gn-protein forms, seven of 27 kDa (Gn27a-g), one of 26 kDa (Gn26) and four of 24 kDa (Gn24a-d). The ralA antibody reacted strongly with the five most basic Gn27 species (a-e), weakly with Gn26 and not at all with Gn27f, Gn27g or Gn24a-d. We conclude that ral gene products account for some but probably not for all of the platelet Gn-proteins. PMID- 2105236 TI - RNA-binding protein-related sequence in a malaria antigen, clustered-asparagine rich protein. AB - Members of the RNA-binding protein superfamily contain RNA binding domains of about 90 amino acids with a highly conserved motif 'GFGF'. Using the conserved motif with some variations G-(F/Y)-(G/A)-(F/Y)-(V/I)-X-(F/Y) as a probe, we screened protein sequences carrying identical amino acids in an NBRF-protein database. It has been found that the C-terminal portion of clustered asparagine rich protein (CARP), a malaria antigen from Plasmodium falciparum, shows an unexpected sequence similarity with the RNA-binding protein superfamily for the C terminal half of the RNA-binding domain. Dot matrix comparisons and alignment of these sequences as well as a statistical test have revealed highly significant sequence similarities. From these analyses, we conclude that the malaria antigen CARP belongs to a large family of the RNA-binding proteins. An evolutionary implication of the sequence similarity was also discussed. PMID- 2105237 TI - Calcium-dependent phospholipid binding proteins associated with the membranes of rabbit skeletal muscle. AB - By using extraction in the presence of Ca2+ and Triton X-100 and then in the presence of EGTA without detergent, a set of Ca2+-dependent phospholipid binding proteins has been identified in the membranes of transverse tubules (T-tubules) and sarcoplasmic reticulum (SR), isolated from rabbit skeletal muscles. Longitudinal SR, junctional SR and T-tubule membranes yielded about 9, 14 and 3.3 micrograms of EGTA-soluble proteins per 1 mg of membrane protein, respectively. In the presence of 1 mM CaCl2, 68 and 33 kDa proteins of T-tubules and junctional SR as well as 30 kDa protein of T-tubules were shown to bind to liposomes made of 1:1 w/w mixtures of (i) phosphatidylcholine and (ii) phosphatidylserine, phosphatidic acid, or phosphatidyl ethanolamine. In the presence of EGTA, the above-mentioned proteins were mostly found in the supernatants. Binding of the proteins with liposomes consisting of pure phosphatidylcholine was negligible. PMID- 2105238 TI - Prochymosin activation by non-aspartic proteinases. AB - Prochymosin can be converted into chymosin by an action of external proteinases. Thus, thermolysin at pH 5.05 converts calf prochymosin into active Phe-chymosin, which is one amino acid longer than chymosin from the N-terminus with a yield of 73%. Even better results were achieved with prochymosin activation by Legionella pneumophila metalloproteinase. Apparently the stretch of prochymosin polypeptide chain adjacent to the normally observed activation point becomes available for an attack by an external proteinase at pH 5.0-6.0. These data indicate that the intermolecular activation pathway might be of physiological importance. PMID- 2105239 TI - Amino acid sequence of photosystem I subunit IV from the cyanobacterium Synechocystis PCC 6803. AB - We describe here the complete amino acid sequence of photosystem I subunit IV from Synechocystis 6803. The molecular mass of 8.0 kDa is lower than in higher plants and Chlamydomonas, due to the lack of a characteristic, proline-rich, N terminal sequence. The remaining sequence exhibits a good conservation, with a hydrophilic and strongly basic N-terminal head followed by two hydrophobic domains. There is no possibility of classical membrane-spanning alpha helices. This component is likely to be one of the most stroma accessible subunits of photosystem I. PMID- 2105240 TI - The cosubstrate NADP(H) protects lysine 601 in the porcine NADPH-cytochrome P-450 reductase against pyridoxylation. AB - Lys601 in NADPH-cytochrome P-450 reductase is modified by reductive alkylation with pyridoxal 5'-phosphate (pyridoxylation). Lys601 is protected against modification by the cosubstrate NADP(H). PMID- 2105241 TI - The gamma subunit of brain G-proteins is methyl esterified at a C-terminal cysteine. AB - The gamma polypeptide of brain G-proteins is carboxyl methylated when the purified beta gamma subunit complex is reconstituted with S-adenosyl-[3H-methyl] L-methionine and a methyltransferase present in detergent-stripped brain membranes. By chromatographic analysis of the 3H-amino acid generated by exhaustive proteolysis and performic acid oxidation of the 3H-methylated beta gamma complex, we show that this modification occurs on the alpha-carboxyl group of a C-terminal cysteine residue. Our result suggests that brain G-protein may undergo multiple covalent modification steps, including proteolytic removal of the three terminal amino acids from the predicted common C-terminal Cys-Xaa-Xaa Xaa sequence, and the methyl esterification of the resulting terminal cysteine residue. This modification is likely to be associated with lipidation at the sulfhydryl group of the same cysteine, which would explain the tight membrane binding property of the brain beta gamma complex. PMID- 2105242 TI - Fasting serum growth hormone and insulin-like growth factor-I and -II concentrations in women with leiomyomata uteri treated with leuprolide acetate or placebo. AB - Eighteen patients with leiomyomata uteri were randomized to receive either leuprolide acetate depot (n = 9) 3.75 mg intramuscularly (IM) or placebo (n = 9) IM every 4 weeks for four injections. Leuprolide acetate treated patients demonstrated a reduction in mean uterine volume of 34% and a decrease in serum estradiol (E2) concentrations from 120 +/- 21 pg/mL (mean +/- standard error) to 16 +/- 9 pg/mL. Leuprolide acetate treated patients also demonstrated significant decreases in serum growth hormone (GH) (3.0 +/- 0.4 ng/mL versus 1.4 +/- 0.4 ng/mL) and insulin-like growth factor-I (IGF-I) concentrations (3.3 +/- 0.4 U/mL versus 1.3 +/- 0.2 U/mL) over the 12 week treatment period. Serum IGF-II levels did not change. Mean uterine volume and serum E2, GH, IGF-I, and IGF-II concentrations did not change in placebo-treated patients. These data suggest that hypoestrogenism is associated with decreases in circulating GH and IGF-I. PMID- 2105243 TI - Cotreatment with human growth hormone and gonadotropins for induction of ovulation: a controlled clinical trial. AB - A randomized, double-blind, placebo-controlled trial of cotreatment with biosynthetic, human sequence, growth hormone (GH), and human menopausal gonadotropins (hMG) for induction of ovulation was performed in 16 women with amenorrhea and anovulatory infertility. Patients were randomly allocated to treatment with hMG + GH (24 IU on alternate days, total dose 144 IU) or hMG + placebo. Those who received placebo were given GH in a subsequent course of treatment. On cotreatment with GH compared with placebo, there was a significant reduction in the required dose of hMG, duration of treatment, and the daily effective dose of gonadotropins. Serum insulin-like growth factor-I (IGF-I) rose during treatment with GH but not with placebo. We conclude that growth hormone augments the response of the human ovary to stimulation by gonadotropins. These results suggest a role for the use of GH in induction of ovulation. PMID- 2105244 TI - Gonadotropin suppression with oral contraceptives before in vitro fertilization. AB - One hundred eighty-one stimulation cycles in which gonadotropin suppression with oral contraceptives (OCs) preceded induction of follicle stimulation (study group) and 113 stimulation cycles without pituitary suppression (control group) were compared. The mean length of ovarian suppression was 35.3 +/- 0.9 days. No spontaneous luteinizing hormone (LH) surges occurred when the use of OC preceded ovarian hyperstimulation, whereas in the control group the incidence of LH surges was 19.5%. The mean amount of human menopausal gonadotropin required was significantly lower in the study group than in the control group (8.9 +/- 0.4 and 10.9 +/- 0.4 ampules, respectively). Significantly more follicles greater than or equal to 1.5 cm in diameter were seen on the day before oocyte retrieval and significantly more oocytes were retrieved per attempt in the group with OC pretreatment. Our data clearly demonstrate that OCs are useful in vitro fertilization stimulation protocols to facilitate scheduling of cycles and to prevent spontaneous LH surges. PMID- 2105245 TI - Prognostic value of the early serum estradiol response to leuprolide acetate in in vitro fertilization. AB - One hundred in vitro fertilization (IVF)-stimulated cycles were analyzed to evaluate the prognostic value of the early follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) response to the agonist action of leuprolide acetate. Four distinct early E2 response patterns were found. Pattern A (n = 41) showed a prompt elevation of E2, followed by a fall by cycle day 4. Pattern B (n = 16) showed a delayed elevation of E2, followed by a fall by cycle day 6. Pattern C (n = 19) showed a persistent elevation of E2. Pattern D (n = 18) lacked the early E2 response. The clinical pregnancy rates per cycle for patterns A, B, C, and D were 46%, 38%, 16%, and 6%, respectively. A baseline serum FSH level greater than 20 mIU/mL was associated with a lower clinical pregnancy rate, although not statistically significant. Baseline serum LH levels and stimulated FSH and LH levels did not predict IVF outcome. We conclude that the early E2 response pattern to leuprolide acetate is the best early prognostic indicator of IVF outcome. PMID- 2105246 TI - Prediction of individual response to controlled ovarian hyperstimulation by means of a clomiphene citrate challenge test. AB - A clomiphene citrate (CC) challenge test was carried out in 114 patients to evaluate the capacity of this test to predict the patient's individual response to controlled ovarian hyperstimulation (COH) performed with a gonadotropin releasing hormone agonist and human menopausal gonadotrophins (hMG) for in vitro fertilization. The sum of follicle-stimulating hormone measured before and after CC intake, is the parameter that correlated best with subsequent response to COH. The upper limit of the reference value for this parameter, established by considering the CC challenge test performed on 26 patients who became pregnant, was 26.03 mIU/mL. Twenty patients who presented a CC challenge test result above the reference value were compared with patients with a normal test result. For these 20 patients, COH required more hMG and was cancelled in 25% of the cases (instead of 1% in the control group). The number of follicles aspirated, oocytes retrieved, and embryos obtained were on average six times lower than in patients with a CC challenge test result within the reference value, and no pregnancy was obtained. We concluded that CC challenge test provides a reliable individual prognosis for the ovarian response to COH. PMID- 2105247 TI - Follicular phase gonadotropin-releasing hormone agonist and human gonadotropins: a better alternative for ovulation induction in in vitro fertilization. AB - Leuprolide acetate was used in 189 in vitro fertilization (IVF) cycles. Patients were allocated prospectively into two groups: In group A (96 cycles), leuprolide acetate was started on the 2nd menstrual cycle day of the actual IVF attempt. In group B (93 cycles), leuprolide acetate was started on the 3rd luteal phase day of the preceding IVF cycle. Ovulation was induced with a combination of pure follicle-stimulating hormone (FSH) and human menopausal gonadotropins (hMG), starting on or before the 5th cycle day, respectively. Leuprolide acetate and gonadotropins were continued until the day of human chorionic gonadotropin (hCG) administration. Follicular aspiration was carried out either by laparoscopy or by transvaginal ultrasound guidance. Group A required a lower number of FSH and hMG ampules than group B; nevertheless, there was no difference in the number of follicles, percentage of preovulatory oocytes or fertilization rate between the groups. The number of embryos transferred was 3.3 and 3.4, respectively. A significantly higher pregnancy rate was observed in group A (40.6% versus 27.7%) and a lower miscarriage rate (22.8% versus 36%) than in group B. In short, this study suggests that there is no need to administer leuprolide acetate routinely during the luteal phase of the preceding IVF cycle. PMID- 2105248 TI - Effects of gonadotropin-releasing hormone agonist and clomiphene citrate on estrogen/progesterone-induced hyperprolactinemia in monkeys. AB - The effects of follicular phase clomiphene citrate (CC) and two regimens of leuprolide acetate on estrogen-progesterone-induced hyperprolactinemia in nonhuman primates were studied. All groups received estradiol (E2) benzoate (12.5 micrograms intramuscularly on cycle days 2 to 33) and progesterone (P) (silastic implant for cycle days 14 to 33). A gonadotropin-releasing hormone agonist (GnRH a) (Lupron 0.5 mg daily, TAP Pharmaceuticals, Chicago, IL) was administered from cycle day 2 to 14 in group II and from day 20 of the previous cycle until cycle day 14 in group III. Oral CC was given on cycle days 3 through 7 in group IV. No significant differences of mean E2 and P concentrations were noted between groups. Neither GnRH-a nor CC had an overall effect on E2/P-induced hyperprolactinemia. However, for the 5-day interval at the onset of the P treatment there was a significant increase in prolactin (PRL) secretion for group II (130.4 +/- 30.6) versus group I (53.9 +/- 3.3), group III (64.4 +/- 11.1), and group IV (68.8 +/- 14.3). This suggests that leuprolide may exert a delayed stimulatory effect on PRL secretion, or that complete suppression of the putative paracrine regulation of PRL stimulation may require more than 13 days of GnRH-a administration. PMID- 2105249 TI - Abdominal paracentesis for the ovarian hyperstimulation syndrome with severe pulmonary compromise. AB - Abdominal paracentesis is a well-tolerated therapeutic alternative to relieve the severe pulmonary compromise caused by severe ascites and pleural effusion in the ovarian hyperstimulation syndrome. An improvement in renal function may be another benefit that deserves further investigation. PMID- 2105250 TI - Detection of the ovulatory-luteinizing hormone surge with an enzyme-linked immunospecific human urinary luteinizing hormone assay: applicability to nonhuman primates. AB - Heterologous antibodies have frequently been used to develop assays in other species. Human urinary LH kits, widely available for predicting the LH surge, offer a unique opportunity to determine the timing of ovulation and mating in nonhuman primates. We tested three commercially available ovulation predictor kits for utility in two macaque species. Midfollicular, midcycle, and castrate urines and their corresponding serum samples were assessed for LH activity using established RIAs as well as urinary ovulation kits. Macaque LH did not sufficiently cross-react with the human urinary anti-LH antibodies in any of the predictor test kits. Although these kits offer excellent results in predicting ovulation by measurement of urinary LH in humans, they appear not to be applicable for urinary LH detection in rhesus nor cynomolgus macaques. PMID- 2105251 TI - Treated and untreated unstable hips in severe cerebral palsy. AB - One hundred patients with severe cerebral palsy (total body involvement) and dislocated hips were examined to determine their level of pain, sitting ability, pelvic obliquity, scoliosis, nursing care difficulties and complications of decubitus ulcers and fractures. 50 of the patients had undergone surgical procedures to treat the hip; 50 had received no treatment. No significant differences were found in the frequency of pain or other complications between the two groups. Nursing care difficulties and the ability to sit did not depend on the status of the hip. Pelvic obliquity and scoliosis were related to the severity of neurological damage rather than to hip stability. These findings suggest that surgical treatment of already dislocated hips of patients with severe cerebral palsy is not helpful. PMID- 2105252 TI - Activation of human neutrophil phospholipase D by three separable mechanisms. AB - Activation of human neutrophils by receptor-mediated agonists, the Ca2+ ionophore A23187, or the protein kinase C activator phorbol myristate acetate all stimulated phospholipase D activity. This was demonstrated by the increased formation of phosphatidic acid, and in the presence of ethanol, phosphatidylethanol (PEt) accumulation. EGTA completely inhibited A23187-induced PEt formation, but only one-half of the fMLP-induced PEt accumulation. Staurosporin, an inhibitor of protein kinase C, strongly inhibited PMA-induced PEt formation, but actually stimulated the formation of PEt in response to fMLP by several-fold. Thus, increased cytosolic Ca2+ and activated protein kinase C can each lead to activation of phospholipase D, but neither is required for receptor-mediated activation of phospholipase D activity. Wortmannin is an irreversible inhibitor of the oxidative burst, but does not inhibit NADPH oxidase or known components of signal transduction. Wortmannin inhibited activation of phospholipase D in response to fMPL. It did not directly inhibit phospholipase D, as the response to A23187 was unaffected. Wortmannin did not inhibit other fMPL stimulated events, such as aggregation or adherence. We conclude that inhibition by wortmannin defines a third pathway to activation of phospholipase D. Further, its effect on phospholipase D correlates with its effect on the respiratory burst. PMID- 2105253 TI - Enterostomy catheter exchange using new polymer-coated guide wire: technical note. AB - The exchange of enterostomy feeding catheters may be facilitated by the use of a recently developed hydrophilic polymer guide wire. This has been found especially useful in the insertion of catheters constructed of polyurethane or silastic-type materials. PMID- 2105254 TI - Misoprostol provides a colonic mucosal protective effect during acetic acid induced colitis in rats. AB - This study determined if intracolonically applied prostaglandin E1 analogue (misoprostol) had a mucosal protective effect in rats with 4% acetic acid-induced colitis. The effects of misoprostol were compared with those of 5-aminosalicylic acid and betamethasone. A single application of 4% acetic acid induced an experimental colitis which was maximal at 2 days and showed spontaneous macroscopic and histologic healing by 12 days. Misoprostol (100 micrograms/kg), but not 5-aminosalicylic acid or betamethasone, administered 30 min before induction of colitis, provided macroscopic and histologic colonic mucosal protection but not protection of in vivo fluid absorption. The mucosal protective effect of misoprostol was time, dose, and diluent volume dependent. In the presence of misoprostol-induced colonic morphologic but not functional absorptive mucosal protection, in vitro unidirectional sodium and chloride flux measurements showed protection of theophylline-stimulated chloride secretion but not sodium absorption. Protection of in vivo colonic fluid absorption, in addition to morphologic protection, could be achieved when misoprostol was administered between 2 and 16 min before induction of colitis or when the highest dose (1000 micrograms/kg) of misoprostol was examined. We conclude that intracolonic misoprostol administration provides unique mucosal protective effects in experimental colitis. PMID- 2105255 TI - Glycosylation of lactase-phlorizin hydrolase in rat small intestine during development. AB - Age-specific changes in glycosylation of rat intestinal lactase-phlorizin hydrolase were analyzed using enzyme immunoprecipitated from microvillus membranes of suckling, weaning, and adult rats, and carbohydrate moieties were examined by lectin affinity binding, metabolic labeling, and neuraminidase treatment. Lectin binding indicated the presence of N-linked and O-linked oligosaccharide chains containing mannose and galactose throughout development. An age-dependent shift in sialic acid and fucose was seen during the period of weaning; no fucose was detectable in lactase-phlorizin hydrolase until after the rats were 20 days of age, whereas sialic acid was reduced in adult lactase phlorizin hydrolase. The presence of sialic acid in suckling intestines and fucose in adult was confirmed by metabolic labeling with appropriate radioactive precursors. Sodium dodecyl phosphate-polyacrylamide gel electrophoresis analysis of immunoprecipitated lactase-phlorizin hydrolase from the proximal and mid small intestine showed two bands of approximately 220 and 130 kilodaltons in all age groups. In the distal part of the adult small intestine, lactase-phlorizin hydrolase appeared as two bands of similar size to those found in the proximal and mid portions. In contrast, during the suckling and weaning periods, these distal bands were approximately 225 and 135 kilodaltons. [35S]-methionine labeling and fluorography of neonatal intestines confirmed these observations. The size difference between proximal and distal small intestines was virtually eliminated by neuraminidase treatment. These data indicate that the core structure of microvillus membrane lactase-phlorizin hydrolase, consisting of both N-linked and O-linked oligosaccharides, remains constant during development, although terminal sugars shift from predominantly sialic acid during the suckling period to fucose in adulthood. This alteration in glycosylation of the protein occurs in a different pattern from the postweaning decline in lactase specific activity. Consequently, age-dependent changes in glycosylation cannot account for the decrease in lactase-phlorizin hydrolase-specific activity observed during development. PMID- 2105256 TI - Effect of total enteral nutrition on the short-term outcome of severely malnourished cirrhotics. A randomized controlled trial. AB - Thirty-five severely malnourished cirrhotic patients were randomized to receive either enteral-tube feeding as the sole nutritional support (n = 16) or an isocaloric, isonitrogenous, low-sodium standard oral diet (n = 19). Both groups were homogeneous regarding age, sex distribution, etiology of liver cirrhosis, history of previous complications, clinical status, liver and renal function, modified Child's score, and nutritional status at admission. The enteral formula diet was energy dense, containing 40 mmol Na/day, whole protein plus branched chain amino acids, medium- and long-chain triglycerides, and maltodextrin. It supplied 2115 kcal/day. The amount of vitamins and trace elements was at the upper limit of the recommended dietary allowances. The orally fed patients were encouraged to eat all meals served. Total enteral nutrition was well tolerated without major complications. Serum albumin and Child's score improved in the enterally fed patients but not in controls. Mortality rate while in the hospital was lower in patients on enteral feeding than in controls (12% vs 47%). These results show that total enteral nutrition is safe and effective in improving the short-term clinical outcome in severely malnourished cirrhotics. PMID- 2105257 TI - Functional and morphological relationships between the feline main pancreatic and bile duct sphincters. AB - To analyze the relationships between the bile duct and main pancreatic duct sphincters, the resistance to flow through these sphincters was studied simultaneously with perfusion techniques in anesthetized cats. Basal flow resistance was higher in the pancreatic sphincter than in the bile duct sphincter. The pressure in one duct system was not affected by the flow in the other. The muscular activities in the sphincters were usually well coordinated. Distention of the upper biliary tract or the pancreatic duct system reduced the flow resistance in both sphincters. Cholecystokinin-8 (0.01 micrograms), duodenal distention, and sublingual glyceryl trinitrate (0.4 mg) also relaxed both sphincters, whereas secretin in a dose that induced pancreatic secretion had no consistent effect. Morphine increased flow resistance in both systems. These functional studies indicate that the 2 sphincters share smooth muscle fibers at the level where the flow resistances arise, and there are thus no grounds for separate control of the sphincters. There was no evidence of a functionally common sphincter ampulla. The conclusions drawn from the manometric results were supported by morphological findings in this study. PMID- 2105258 TI - Effects of ponalrestat on depressor responses to arachidonic acid in streptozotocin-diabetic rats. AB - 1. This study measured reductions in diastolic blood pressure to arachidonic acid (AA, 0.125-2.0 mg/kg i.v.) in 14-day streptozotocin-diabetic (60 mg/kg i.v.) and control rats anaesthetized with pentobarbitone (50-70 mg/kg i.p.) having been treated acutely or chronically with saline or ponalrestat (25 mg/kg p.o. 1 hr prior to anaesthesia, or 25 mg/kg p.o. daily for 14 days). 2. Streptozotocin treated diabetic rats displayed reduced sensitivity to depressor effects of AA (0.125-2.0 mg/kg) when compared with controls. 3. Acute treatment with ponalrestat did not change responses to AA in controls or diabetics, whereas chronic treatment resulted in a small increase in depressor responses to AA (0.125, 0.25 and 2.0 mg/kg) in diabetics but not controls. 4. The mechanism of this action of ponalrestat remains to be elucidated, although the results are compatible with the hypothesis that increased polyol pathway activity may affect responses to, or metabolism of eicosanoids. PMID- 2105259 TI - Postmortem changes in endothelium-dependent and independent responses of porcine coronary arteries. AB - 1. Studies were performed in porcine left circumflex coronary arteries to determine the time course of changes in their responses to smooth muscle and endothelial cell agonists following death. 2. The pigs were kept at room temperature for 3, 6, 12 and 24 hr after death before removing the arteries, and the responses compared with fresh arteries. Rings of the arteries were mounted in organ chambers filled with modified Krebs-Ringer solution for isometric tension recording. 3. Fresh rings with endothelium relaxed with stretching, whereas 3- and 6-hr rings developed an increase in tension and often rhythmic activity. In 3 hr rings, there were diminished contractile responses to KCl and serotonin. The contractile responses to prostaglandin F2 alpha were depressed at 3 and 6 hr. 4. At 6 hr, rings from six of 14 pigs failed to contract and the responses of the other eight to histamine and serotonin but not to KCl or acetylcholine, were depressed compared to fresh rings. 5. 6 hr after death endothelium-mediated relaxations to bradykinin and calcium ionophore A-23187 were depressed while endothelium-mediated as well as direct smooth muscle relaxation by adenosine diphosphate did not change. 6. These studies indicate that caution must be observed in interpreting the findings in autopsy specimens examined as early as 3 hr after death. PMID- 2105260 TI - The relationship between homotropic and heterotropic cooperativity for angiotensin receptors in smooth muscle. AB - 1. Angiotensin-induced contraction of smooth muscle is accompanied by both homotropic (receptor-receptor) and heterotropic (receptor-G protein) cooperativity. 2. Binding constants for angiotensins II and III at uterine smooth muscle receptors have been compared in bioassays and binding assays, using the competitive antagonist Sarmesin to verify the binding assay/bioassay interrelationship. 3. Agonist affinities determined from binding studies in the presence of GTP/S were found to be similar to the affinities observed in responding rat uterine tissues under conditions which eliminate positive homotropic cooperativity, suggesting that heterotropic cooperativity and homotropic cooperativity are interdependent events for smooth muscle contraction. 4. The data are consistent with an allosteric or autosteric mechanism of receptor function involving cooperativity between two agonist binding sites on the receptor. 5. The model has been used to calculate homotropic efficacies for angiotensins II and III from bioassay data and binding data, respectively. PMID- 2105261 TI - Changes in brain biogenic monoamines induced by the nootropic drugs adafenoxate and meclofenoxate and by citicholine (experiments on rats). AB - 1. The effects of Adafenoxate (Adf), meclofenoxate (Mf) and citicholine (CCh) administered at a daily dose of 100 mg/kg for 7 days on the levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the frontal cerebral cortex, striatum, hippocampus and hypothalamus of rats were studied. 2. Adafenoxate increased the NA level in the striatum and decreased it in the hypothalamus; it increased the DA level in the cerebral cortex and hypothalamus and decreased it in the striatum; it increased the 5-HT level in the cerebral cortex and decreased it in the hippocampus. 3. Meclofenoxate decreased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the hippocampus and hypothalamus and the 5-HT level in the cerebral cortex, striatum, hippocampus and hypothalamus. 4. Citicholine increased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the striatum and the 5-HT level in the cerebral cortex, striatum and hippocampus. 5. An attempt is made to explain some similarities and differences in the behavioral effects of the drugs tested (and those observed in other studies) by the changes they induce in brain biogenic monoamines. PMID- 2105262 TI - Human chorionic gonadotropin, follicle-stimulating hormone, and luteinizing hormone in patients with epithelial ovarian carcinoma. AB - Plasma levels of human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were studied in patients with epithelial ovarian carcinoma prior to and during chemotherapy. Blood samples were drawn for radioimmunoassay at monthly intervals. Plasma concentrations were compared to those of three different control groups: healthy post-menopausal women (PM), fertile women in the follicular phase of the menstrual cycle (FPh), and postmenopausal women with nongynecologic disseminated malignant disease (DMD). The hCG level was elevated in women with great tumor burden, such as large tumor volume, FIGO stage IV, and histologic type V. LH and FSH levels showed the reverse pattern. hCG concentration decreased during chemotherapy, whereas LH increased. Initial plasma concentrations were not found to have prognostic importance. We discuss the possibility that hCG is produced by the tumor, which stimulates steroid hormone production by the stroma, which, in turn, exerts negative feedback on FSH production by the pituitary. PMID- 2105263 TI - LTC advocate proposes Part C for Medicare. PMID- 2105264 TI - Physician practices go under the microscope. AB - Last spring, executives at Charles E. Still Osteopathic Hospital, Jefferson City, MO, distributed individual practice profiles to each member of the medical staff. The physicians threw the computer printouts into the nearest trash can. However, things have improved since then, and the physicians eventually became intrigued by the data. Hospital CEOs nationwide can identify with this experience. According to Hospitals survey data, 51 percent of hospital executives are generating practice profiles for medical staff members, but of this number, only 55 percent are sharing the data with the physicians. The question is: What's the best way to collect and share this profile information? This issue's cover story looks at how several hospital executives answered this question. PMID- 2105265 TI - NAIC (National Association of Insurance Commissioners) chief pushes LTC reform. PMID- 2105266 TI - Neurofibromatosis-1: a maximum likelihood estimation of mutation rate. AB - Methods of classical segregation analysis were applied to a sample of 129 sibships with one or more individuals affected by neurofibromatosis-1 (NF-1). The sample consists only of subjects with NF-1; all the probands had been referred for genetic counselling because of cafe-au-lait spots, and a diagnostic protocol was invariably applied. No deviation from the segregation ratio expected for a fully penetrant Mendelian dominant gene was observed. A maximum likelihood estimate of the proportion of sporadic cases was obtained, and the mutation rate was estimated to be 6.5 x 10(-5) gametes per generation (95% CI 5.0-8.1). PMID- 2105267 TI - Distribution of prostaglandins E2 and 6-keto-F1 alpha production in dog kidneys. AB - Little is known about the distribution of prostaglandin E2 (PGE2) and prostacyclin (PGI2) production in the canine kidney. To determine the basal and stimulated profiles of PGE2 and PGI2 production along the corticomedullary axis of the dog kidney, a slice (0.5 mm thick, 10-50 mg) was obtained from six equally spaced zones along the axis (zone 1, medullary crest; zones 2 and 3, inner medulla; zone 4, outer medulla; and zones 5 and 6, cortex) and was divided into equal halves. One half of the slice was incubated with Krebs-Ringer buffer containing arachidonic acid (6.6 x 10(-4) M), bradykinin (9.4 x 10(-6) M), or indomethacin (10(-5) M), whereas the remaining half of each slice was similarly incubated in Krebs-Ringer buffer alone. The production of PGE2 and 6-keto-PGF1 alpha (the stable metabolite of PGI2) was determined by radioimmunoassay. Under basal conditions, both PGE2 and 6-keto-PGF1 alpha were highest in the innermost zones of the inner medulla (PGE2, 3,328 +/- 549 pg/mg; 6-keto-PGF 1 alpha, 1,611 +/- 129 pg/mg) and decreased exponentially to low levels in the cortex (PGE2, undetectable; 6-keto-PGF1 alpha, 13 +/- 2 pg/mg); this production was inhibited by indomethacin. Arachidonic acid significantly increased the production of PGE2 in all zones of the kidney and the production of 6-keto-PGF1 alpha only in zones 3-6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105268 TI - Reciprocal effects of dexamethasone on vasodilatory responses to arachidonic acid and prostanoids in the isolated perfused rabbit kidney. AB - We reported that dexamethasone treatment of rabbits causes a reduction in renal vasoconstrictor responses to prostaglandin F2 alpha and U46619, an agonist at the thromboxane-endoperoxide receptor, but not to phenylephrine. The purpose of this study was to examine if dexamethasone treatment can affect the renal vasodilatory responses to prostacyclin (PGI2) and prostaglandin E2 (PGE2) in isolated Krebs perfused kidneys constricted with phenylephrine. In kidneys from dexamethasone treated rabbits, the vasodilatory response to PGI2 was reduced by 57%, whereas that to PGE2 was converted to a vasoconstrictor response. This effect of dexamethasone appears to be specific in that the renal vasodilatory responses to forskolin and to sodium nitroprusside were not affected by the steroid. Contrasting with the inhibitory effect of dexamethasone on prostanoid-induced renal vasodilation, treatment with dexamethasone augmented the renal vasodilatory response to arachidonic acid; for example, arachidonic acid, at 10 micrograms decreased perfusion pressure by 24.8 +/- 5.4 and 49.0 +/- 5.6 mm Hg in kidneys from vehicle- and dexamethasone-treated rabbits, respectively. The enhanced vasodilatory effect of arachidonic acid could not be attributed to increased renal formation of PGE2 and PGI2. In conclusion, dexamethasone interferes with prostanoid-mediated renal vasodilation, which is not associated with an impairment in renal responsiveness to direct activators of adenylate cyclase and guanylate cyclase. The reciprocal effect of dexamethasone on the renal vascular responses to arachidonic acid and vasodilatory prostanoids are indicative of a previously unrecognized influence of glucocorticoids on the renal arachidonate prostaglandin system. PMID- 2105269 TI - Immunization against anthrax with aromatic compound-dependent (Aro-) mutants of Bacillus anthracis and with recombinant strains of Bacillus subtilis that produce anthrax protective antigen. AB - The safety and efficacy of five prototype, live anthrax vaccines were studied in Hartley guinea pigs and CBA/J and A/J mice. Two of the strains, Bacillus anthracis FD111 and FD112, are Aro- mutants derived by Tn916 mutagenesis of B. anthracis UM23-1. Bacillus subtilis PA1 and PA2 contain a recombinant plasmid, pPA101 or pPA102, respectively, that carries the gene from B. anthracis encoding synthesis of protective antigen (PA). The final strain, B. subtilis PA7, was isolated in this study from B. subtilis DB104 transformed with pPA101. All five strains were less virulent in guinea pigs and A/J and CBA/J mice than the toxinogenic, nonencapsulated B. anthracis veterinary vaccine Sterne strain. A/J and CBA/J inbred mice represent strains that are innately susceptible and resistant, respectively, to the Sterne strain. These differences in susceptibility are due to differences in ability to produce complement component 5. In guinea pigs, immunization with PA1 or PA2 vegetative cells or PA7 spores protected greater than or equal to 95% from an intramuscular spore challenge with the virulent, "vaccine-resistant" B. anthracis Ames strain. Strain PA2 vegetative cells and strain PA7 spores were as effective as the Sterne strain in Sterne resistant CBA/J mice, protecting 70% of the mice from Ames strain spore challenge. Immunization with FD111 or FD112 vegetative cells fully protected guinea pigs from challenge. Immunization with FD111 cells protected up to 100% of CBA/J mice and up to 70% of A/J mice. PMID- 2105270 TI - Localization of the cleavage site specificity determinant of Haemophilus influenzae immunoglobulin A1 protease genes. AB - Immunoglobulin A1 (IgA1) proteases are produced by a number of different species of bacteria which cause infection at human mucosal surfaces. The sole substrate of these proteases is human IgA1. Cleavage is within the hinge region of IgA1, although there is variability in the exact peptide bond within the hinge region that is cut by a particular protease. The cleavage site of the Haemophilus influenzae type 1 protease is located four amino acids from the cleavage site of the type 2 enzyme. In this study, the region of the H. influenzae IgA1 protease gene (iga) that determines the cleavage site specificity was localized through the comparison of the type 1 and type 2 genes and the construction and analysis of type 1-type 2 hybrid genes. The hybrid genes were generated by in vivo and in vitro techniques which facilitated the selection and screening of randomly generated hybrids. The cleavage site determinant was found to be within a 370 base-pair region near the amino-terminal coding region, in one of two large areas of nonhomology between the two types of H. influenzae iga genes. DNA sequence analysis of the cleavage site determinant and surrounding regions did not reveal a simple mechanism whereby one enzyme type could be converted to the other type. Comparison of the type 2 gonococcal IgA1 protease gene to the two Haemophilus genes revealed a significant amount of homology around the cleavage site determinant, with the two type 2 genes showing greater homology. PMID- 2105271 TI - Expression of the Bacillus anthracis protective antigen gene by baculovirus and vaccinia virus recombinants. AB - The gene encoding Bacillus anthracis protective antigen (PA) was modified by site directed mutagenesis, subcloned into baculovirus and vaccinia virus plasmid transfer vectors (pAcYM1 and pSC-11, respectively), and inserted via homologous recombinations into baculovirus Autographa californica nuclear polyhedrosis virus or vaccinia virus (strains WR and Connaught). Expression of PA was detected in both systems by immunofluorescence assays with antisera from rabbits immunized with B. anthracis PA. Western blot (immunoblot) analysis showed that the expressed product of both systems was slightly larger (86 kilodaltons) than B. anthracis-produced PA (83.5 kilodaltons). Analysis of trypsin digests of virus expressed and authentic PA suggested that the size difference was due to the presence of a signal sequence remaining with the virus-expressed protein. Immunization of mice with either recombinant baculovirus-infected Spodoptera frugiperda cells or with vaccinia virus recombinants elicited a high-titer, anti PA antibody response. PMID- 2105272 TI - Synthesis and characterization of Escherichia coli O18 O-polysaccharide conjugate vaccines. AB - Nontoxic, serologically reactive O polysaccharide was derived from Escherichia coli O18 lipopolysaccharide by acid hydrolysis, extraction with organic solvents, and gel filtration chromatography. Oxidized O polysaccharide was covalently coupled to either Pseudomonas aeruginosa toxin A or cholera toxin by using adipic acid dihydrazide as a spacer molecule in the presence of carbodiimide. The resulting conjugates were composed of approximately equal amounts of O polysaccharide and protein and were nontoxic and nonpyrogenic. Both conjugates engendered an immunoglobulin G antibody response in rabbits that recognized native O18 lipopolysaccharide. Such antibody was able to promote the uptake and killing of an E. coli O18 strain bearing the K1 capsule by human polymorphonuclear leukocytes. Immunoglobulin G isolated from the sera of rabbits immunized with either conjugate afforded protection against an E. coli O18 challenge when passively transferred to mice. PMID- 2105273 TI - Characterization of a cell population which amplifies the anticryptococcal delayed-type hypersensitivity response. AB - Cell-mediated immunity to Cryptococcus neoformans can be detected by delayed-type hypersensitivity (DTH) to a culture filtrate antigen of C. neoformans. Recently, we have identified a population of cells in spleens of mice immunized with cryptococcal antigen that, when transferred to recipient mice at the time of immunization, amplifies the anticryptococcal DTH response. If the cell donor mice are treated with cyclosporin A during induction of the anticryptococcal DTH response, the amplifier cells are not induced, whereas the cells which transfer DTH (TDH cells) are induced. The purpose of this study was to characterize the amplifier cells with respect to their surface and functional properties and, in so doing, determine whether or not the amplifier cells are analogous to long lived memory cells. We demonstrated that the amplifier cells were nylon-wool nonadherent, antigen-specific, CD4 (L3T4+ Lyt-2-) T lymphocytes which appear in the spleens of mice 5 days postimmunization with cryptococcal culture filtrate antigen in complete Freund adjuvant. The amplifier T (Tamp) cells are not considered to be memory cells because they are relatively short-lived, being present 14 but not 18 days after the stimulating immunization. Moreover, the amplified anticryptococcal DTH response does not fulfill the criteria of the typical secondary immune (anamnestic) response in that the amplified response does not appear early relative to the appearance of the primary anticryptococcal DTH response, and it does not persist longer than the primary DTH response. We speculate that Tamp cells are not long-lived memory cells but rather act in a T helper cell capacity to amplify the anticryptococcal DTH response. PMID- 2105274 TI - Involvement of gamma interferon in antibody enhancement by adjuvants. AB - In a previous study the adjuvant action of a monophosphoryl lipid A, a nontoxic derivative of endotoxic lipopolysaccharide (LPS), was found to be negated by a monoclonal anti-gamma interferon (anti-IFN-gamma) antibody. The present investigation centered on three other adjuvants of diverse microbial origins, testing for their capacity to affect the release of IFN-gamma as an explanation for their antibody-enhancing action. The adjuvant action of each of the three, a wild-type LPS, synthetic poly(A)-poly(U) complexes, and a synthetic muramyl dipeptide, n-acetylmuramyl-L-alanyl-D-glutaminyl-n-butyl ester (murabutide), was transferable by adjuvant-stimulated T cells to normal spleen cells on coculture. Supernatant fluids from these T cells contained increased levels of IFN-gamma. Addition of a monoclonal anti-IFN-gamma antibody to adjuvant-stimulated spleen cell cultures reduced the adjuvant action by approximately one-half. Removal of natural killer cells from spleen cell populations prior to culture with antigen had no effect on the enhancement induced by LPS and monophosphoryl lipid A. It was concluded that the enhancement induced by the adjuvants LPS, poly(A)-poly(U), and murabutide is mediated in part by their action on T cells resulting in release of IFN-gamma suggesting activation of a common transmembrane signal. PMID- 2105275 TI - Effects of Pseudomonas aeruginosa elastase on alveolar epithelial permeability in guinea pigs. AB - Elastase-deficient mutants of Pseudomonas aeruginosa are less virulent than the wild type and are easily cleared from the lungs of guinea pigs. The effect of P. aeruginosa elastase on lung epithelium, however, is not yet understood. We addressed the hypothesis that breach of the epithelial barrier by elastase from P. aeruginosa allows invading organisms and toxic substances to penetrate the interstitium. We measured the clearance of aerosolized technetium-labeled albumin (molecular weight, 69,000) from the lungs of anesthetized guinea pigs with the aid of a gamma camera and a dedicated computer. Aerosols of the elastase (0.1 to 5 micrograms) increased the rate of clearance of labeled albumin from the lungs in proportion to the elastase dose. Electron microscopic studies using horseradish peroxidase as a tracer revealed that elastase interrupts intercellular tight junctions of the epithelial lining, thereby increasing the permeability to macromolecules. The amounts of elastase used in this report did not cause interstitial or alveolar edema, as determined by both postmortem extravascular lung water volume measurement and morphological examination. The data indicate that the elastase is a potentially important virulence factor in acute lung infection. PMID- 2105276 TI - Molecular characterization of the Clostridium difficile toxin A gene. AB - The gene encoding the toxin A protein of Clostridium difficile (strain VPI 10463) was cloned and sequenced. The coding region of 8,133 base pairs had a mol% G + C of 26.9 and encodes 2,710 amino acids. The deduced polypeptide has a molecular mass of ca. 308 kilodaltons. Nearly a third of the gene, at the 3' end, consists of 38 repeating sequences. The repeating units were grouped into two classes, I and II, on the basis of length and the low levels of DNA sequence similarities between them. There were seven class I repeating units, each containing 90 nucleotides, and 31 class II units, which, with two exceptions, were either 60 or 63 nucleotides in length. On the basis of DNA sequence similarities, the class II repeating units were further segregated into subclasses: 7 class IIA, 13 class IIB, 5 class IIC, and 6 class IID. The dipeptide tyrosine-phenylalanine was found in all 38 repeating units, and other amino acid sequences were unique to a specific class or subclass. This region of the protein has epitopes for the monoclonal antibody PCG-4 and includes the binding region for the Gal alpha 1 3Gal beta 1-4GlcNAc carbohydrate receptor. Located 1,350 base pairs upstream from the toxin A translation start site is the 3' end of the toxin B gene. Between the two toxin genes is a small open reading frame, which encodes a deduced polypeptide of ca. 16 or 19 kilodaltons. The role of this open reading frame is unknown. PMID- 2105277 TI - Variation in expression of class 1 and class 5 outer membrane proteins during nasopharyngeal carriage of Neisseria meningitidis. AB - Accidental nasopharyngeal colonization of a laboratory worker by a human disease isolate of Neisseria meningitidis allowed us to examine the variation in expression of outer membrane components and the host humoral response over time. There were quantitative differences in class 1 outer membrane protein expression in nasopharyngeal isolates obtained at different times. Isolates also showed phase variation of all four class 5 outer membrane proteins produced by the colonizing strain. After colonization, we detected new host serum immunoglobulin G antibodies directed against class 1, class 5, and H.8 outer membrane proteins. PMID- 2105278 TI - Influence of different regions of the H-2 complex on the rate of clearance of Salmonella typhimurium. AB - The rate of clearance of Salmonella typhimurium from the mouse spleen is under H 2 linked genetic control. The results of the present study, with H-2 recombinant mice on a C57BL/10 background, suggest the involvement of at least two loci, one in the D region and the other in the K-A alpha chromosomal segment. PMID- 2105279 TI - The effect of the E2 prostaglandin enprostil, and the somatostatin analogue SMS 201 995, on the growth of a human gastric cell line, MKN45G. AB - The effect of enprostil and the somatostatin analogue SMS 201 995 on the growth of a clonal variant of the human gastric adenocarcinoma cell line, MKN45, was studied. The derived cell line grew twice as fast as MKN45 when grown as a xenograft line in nude mice. However, it did not respond trophically to gastrin either in vitro or in vivo (unlike MKN45) although it possessed the same number of gastrin receptors as the parental line. Gastrin production by the cell line during in vitro culture was twice that of MKN45; thus, the cell line was denoted MKN45G. When MKN45G was grown as xenografts in nude mice (n = 10/group), enprostil (20 micrograms/kg/day) significantly inhibited tumour growth when administered continuously by an osmotic mini-pump from day 1 to day 7 of a 20-day experiment, and induced tumour regression when administered from day 7 to day 14. Enprostil reduced postprandial serum gastrin levels when administered from day 7 to day 14 and prevented gastrin release by MKN45 in vitro. SMS 201 995 at doses of 25 and 240 micrograms/kg/day induced tumour regression when administered from day 1 to day 7 and the former dose reduced post-prandial serum gastrin levels at day 5. Gastrin release by MKN45G was not affected by SMS 201 995 in vitro, thus its effect may not be mediated directly via gastrin, requiring interaction between other hormones or growth factors in the in vivo situation. PMID- 2105280 TI - Effect of prostacyclin on coronary occlusion in acute myocardial infarction. AB - Prostacyclin is a powerful inhibitor of platelet aggregation and induces relaxation of vascular smooth muscle. We have studied the coronary effects of high local concentrations of prostacyclin in 17 patients during the early stages of acute myocardial infarction. We infused graded concentrations of intracoronary prostacyclin and compared the effects to those of intracoronary isosorbide dinitrate before and after an intracoronary infusion of streptokinase. Considerable dilation of the infarct-related stenosis may follow local infusions of prostacyclin in some patients. In general, however, dilation of the infarct related stenosis or coronary recanalization did not result from infusion of prostacyclin. PMID- 2105281 TI - Lack of T6 induction on human corneal Langerhans cells in vitro. AB - Previous studies have shown that Langerhans cells (LC) in normal human corneas differ from their counterparts in other epithelia (eg, skin, gingival, cervical) by their lack of the thymocyte antigen T6 on their membranes. In those studies only three out of four very young infant corneas (newborn, 3-day-, 8-day-old) have displayed positive T6 staining to date. Corneas from older infants and adults have demonstrated no such staining. This study tested the capacity of corneal LC to express T6 by in vitro induction with several immunomodulating agents. Human gamma interferon (IFN gamma was tested at 1000 U/ml, 500 U/ml and 100 U/ml. Interleukin-1 (IL-1) was tested at 100 U/ml, 50 U/ml and 20 U/ml. Thymopoietin pentapeptide (TP-5) was tested at 10 micrograms/ml, 1 micrograms/ml and 0.1 microgram/ml. Combinations of these agents were also tested in a similar fashion. None of these immunomodulating agents or combinations of them were able to induce T6 expression on normal corneal LC. This may reflect an innate incapacity of these cells to express this antigen or dosage requirements in excess of those tested. PMID- 2105282 TI - Modulation of HLA antigen expression on conjunctival fibroblasts by gamma interferon. AB - We investigated the ability of recombinant human gamma-interferon (rhIFN-gamma) to induce class II HLA antigen expression on human conjunctival fibroblasts in cell culture. Cultures were established by explanting subconjunctival tissue from normal donor globes. Fibroblasts were treated with rhIFN-gamma at concentrations ranging from 1 to 500 units/ml and incubated for 1, 3 and 6 days. HLA antigens were detected by immunofluorescence using monoclonal antibodies in conjunction with flow cytometry. Class I antigen was identified using a monoclonal antibody directed against Beta-2 microglobulin (a component of the class I antigen complex). Class II histocompatibility antigens were detected using monoclonal antibodies specific for HLA-DR, HLA-DP and HLA-DQ. Class I antigen was present on all cells prior to induction and showed a trend toward increased density after treatment with rhIFN-gamma. Class II antigens were absent before induction with rhIFN-gamma. After treatment with rhIFN-gamma, class II antigens were induced in a dose- and time-dependent fashion. HLA-DR expression was most sensitive to induction by rhIFN-gamma, followed by HLA-DP, and then HLA-DQ. The up-regulation of HLA class I antigen expression and the inducible expression of class II antigens following exposure to rhIFN-gamma suggest that conjunctival fibroblasts have the potential to participate in immunologic diseases of the external eye. PMID- 2105283 TI - Pharmacologic modulation of vascular permeability in ocular allergy in the rat. AB - Evans blue (EB) dye extravasation has been used as a reliable and objective parameter of the increased vascular permeability of an allergic conjunctivitis experimental rat model that closely mimics human ocular allergy. Five male Wistar rats, previously immunized (Group 1), had DL-dithiothreitol (DTT) applied topically to one eye 15 min prior to topical challenge with egg albumin (EA). The fellow eye (control) received phosphate buffered saline (PBS) 15 min prior to receiving EA. Immediately prior to challenge, the rats were injected intravenously with EB. After 30 min, the animals were killed and the dye extracted from the eyes. The intensity of EB extravasation was determined by spectrophotometry at 620 nm. EB extravasation was significantly higher in the eyes that received DTT than in those that received PBS. Groups 2, 3 and 4 of nonimmunized rats served as additional controls: Group 2 for DTT toxicity, Group 3 as a proof of the reaginic antibody mediation and Group 4 as a control of EB extravasation under normal conditions. Five additional groups of five rats each were immunized and both eyes of each rat received DTT 15 min before EA challenge. One eye of each rat received 0.1% dexamethasone sodium phosphate topically (Group 5), 0.1% pyrilamine maleate (Groups 6 and 7), and 2% disodium cromoglycate (DSCG) (Groups 8 and 9). The fellow eye received the solvent of each drug topically (control). In the eyes treated with antiallergic drugs, EB extravasation decreased 40% for dexamethasone, 44.1% and 10.4% for pyrilamine, and 51.4% and 51.2% for DSCG. PMID- 2105284 TI - Thrombolytic therapy in acute myocardial infarction. PMID- 2105285 TI - Normal tissue reactions and complications following high-energy neutron beam therapy. II: Complication rates adjusted for censoring. AB - A dose response analysis was performed on patients at risk for significant radiation injuries following neutron radiotherapy. Complication rates were calculated at various dose intervals using a maximum likelihood method that is formally equivalent to the product limit estimator of survival. The variance of each complication rate was used to weight a logistic regression on log dose. The treatment sites that were analyzed were head and neck, pelvis, thorax, and pancreas. Except for osteomyelitis of the mandible, complications of all types were considered collectively at each site and dose increment since there were too few complications to determine dose response functions for individual types of injuries. The head and neck was observed to be the site with the highest tolerance to radiation whereas the thorax was the most sensitive site. PMID- 2105286 TI - Pitfalls in the use of high energy X rays to treat tumors in the lung. AB - The problem of central axis dose reduction for high energy photon beams of small cross-sectional area traversing normal lung tissue is well known. An additional problem, which may be not as well appreciated, is the loss of electronic equilibrium on the periphery of high energy photon beams, resulting in an increase in the penumbra occurring in lung. We have compared profiles of x-ray beams ranging in energy from 4 MV to 18 MV. The profiles were measured at 10-cm depth in unit-density and lung-density (0.26) phantoms. At the highest energy the 20% to 80% physical penumbra width was measured to be 7.5 mm in the unit-density material, whereas in the lung phantom the width was 18 mm. At 4 MV the situation was reversed; that is, the penumbra was slightly smaller in the lung phantom. Most computer programs for radiation therapy treatment planning do not take into account this change in beam profile when calculating dose in the lung. As a result, unanticipated underdosing inside the field and greater dose outside the field can occur when high-energy X rays are used. PMID- 2105287 TI - Serologic and histologic diagnosis of toxoplasmic abortions in sheep in Oregon. AB - Between 1983 and 1989, we examined 586 fetuses and dead lambs submitted to a diagnostic laboratory in Oregon. Toxoplasmosis was diagnosed in 74 (12.6%), campylobacteriosis in 89 (15.2%), chlamydiosis in 75 (12.8%), miscellaneous infections in 153 (26.1%), noninfectious causes in 37 (6.3%), and undetermined causes in 158 (27.0%). Detection of Toxoplasma gondii agglutinating antibodies (greater than or equal to 20) in body fluids or heart serum was considered specific for the diagnosis of toxoplasmosis in ovine fetuses or lambs. Toxoplasma gondii antibody titers (reciprocal) in 285 fluids from fetuses or dead lambs were less than 20 (64.5%), 20 (4.5%), 40 (1.7%), 80 (0.7%), 160 (2.1%), 320 (1.7%), 640 (4.9%), 1,280 (2.8%), 2,560 (4.5%), 5,120 (3.8%), 10,240 (2.1%), and greater than or equal to 20,480 (6.3%). PMID- 2105288 TI - Total parenteral nutrition in a neonatal llama. AB - Total parenteral nutrition reversed cachexia, dehydration, and electrolyte abnormalities in a neonatal llama suffering from prolonged diarrhea. Complications were not observed during the 8 days that IV-administered fluids and nutritional support were provided. PMID- 2105289 TI - Peptidoglycan-associated polypeptides of Mycobacterium tuberculosis. AB - Important protein-based immunoreactivities have long been associated with the cell wall core of mycobacteria. In order to explore the molecular basis of such activities, purified cell walls of Mycobacterium tuberculosis were extracted with sodium dodecyl sulfate to produce an insoluble residue composed of the mycolylarabinogalactan-peptidoglycan complex and about 2% of unextractable protein. Treatment of the product from an avirulent strain of M. tuberculosis with trifluoromethanesulfonic acid released a single polypeptide with a molecular size of 23 kilodaltons, accounting for all of the insoluble cell wall protein. Extensive purification and then analysis of the 23-kilodalton protein demonstrated the absence of diaminopimelic acid, muramic acid, or other peptidoglycan components, pointing to either a novel linkage between protein and peptidoglycan or a noncovalent but tenacious association. The released 23 kilodalton protein showed amino acid homology and other similarities to the outer membrane protein OmpF of Escherichia coli. Although a similar product was released in small quantities from cell walls of the virulent M. tuberculosis Erdman and H37Rv by lysozyme treatment, the cell walls of virulent bacilli were dominated by the presence of poly-alpha-L-glutamine, accounting for as much as 10% of their weight. The poly-alpha-L-glutamine was successfully separated from the cell wall proper, demonstrating again the absence of a covalent association between peptidoglycan and the polymer. The antigenicity of these products is demonstrated, and their roles vis-a-vis analogous polypeptides from other bacteria in immunogenicity, pathogenicity, and bacterial physiology are discussed. PMID- 2105290 TI - Isolation and characterization of a novel extracellular metalloprotease from Bacillus subtilis. AB - We have isolated and characterized two minor extracellular proteases from culture supernatants of a strain of Bacillus subtilis containing deletion mutations of the genes for the extracellular proteases subtilisin (apr) and neutral protease (npr) and a minor extracellular protease (epr) as well as intracellular serine protease-I (isp-1). Characterization studies have revealed that one of these enzymes is the previously described protease bacillopeptidase F. The second enzyme, the subject of this report, is a novel metalloprotease, which we designate Mpr. Mpr is a unique metalloprotease that has been purified to apparent homogeneity by using both conventional and high-performance liquid chromatography procedures. Mpr has a molecular mass of approximately 28 kilodaltons on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a basic isoelectric point of 8.7. The enzyme showed maximal activity against azocoll at pH 7.5 and 50 degrees C. Mpr was inhibited by dithiothreitol and a combination of beta mercaptoethanol and EDTA. Activity was moderately inhibited by beta mercaptoethanol and EDTA alone as well as by cysteine and citrate and only marginally by phosphoramidon 1,10-phenanthroline and N-[N-(L-3-trans carboxyoxiran-2-carbonyl)-L-leucyl]-agmatine. Mpr was not inhibited by phenylmethylsulfonyl fluoride. In addition, Mpr showed esterolytic but not collagenolytic activities. Our studies suggest that Mpr is a secreted metalloprotease containing cysteine residues that are required for maximal activity. PMID- 2105291 TI - Gene encoding a novel extracellular metalloprotease in Bacillus subtilis. AB - The gene for a novel extracellular metalloprotease was cloned, and its nucleotide sequence was determined. The gene (mpr) encodes a primary product of 313 amino acids that has little similarity to other known Bacillus proteases. The amino acid sequence of the mature protease was preceded by a signal sequence of approximately 34 amino acids and a pro sequence of 58 amino acids. Four cysteine residues were found in the deduced amino acid sequence of the mature protein, indicating the possible presence of disulfide bonds. The mpr gene mapped in the cysA-aroI region of the chromosome and was not required for growth or sporulation. PMID- 2105292 TI - Induction of levansucrase in Bacillus subtilis: an antitermination mechanism negatively controlled by the phosphotransferase system. AB - The target of the induction by sucrose of the levansucrase gene is a transcription terminator (sacRt) located upstream from the coding sequence, sacB. The two-gene locus sacX-sacY (formerly sacS) and the ptsI gene were previously shown to be involved in this induction. ptsI encodes enzyme I of the phosphoenolpyruvate-dependent phosphotransferase system. SacX is strongly homologous to sucrose-specific phosphotransferase system-dependent permeases. SacY is a positive regulator of sacB. Here we show that SacY is probably an antiterminator interacting directly with sacRt, since in Escherichia coli the presence of the sacY gene stimulates the expression of a reporter gene fused downstream from sacRt. Missense mutations affecting sacY were sequenced, and the sacB regulation was studied in isogenic strains carrying these mutations or in vitro-generated mutations affecting sacX, sacY, or ptsI. The phenotype of double mutants suggests a model in which SacX might be a sucrose sensor that would be phosphorylated by the phosphotransferase system and, in this state, could inhibit the SacY antiterminator. Exogenous sucrose, or a mutation inactivating the phosphotransferase system, would dephosphorylate SacX and allow antitermination at sacRt. PMID- 2105293 TI - The cisA cistron of Bacillus subtilis sporulation gene spoIVC encodes a protein homologous to a site-specific recombinase. AB - The nucleotide sequence of the sporulation gene spoIVC cisA in Bacillus subtilis was determined and found to encode a protein of 500 amino acid residues with a calculated molecular weight of 57,481, which is in good agreement with the size of the gene product estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The amino acid sequence of the N-terminal region of this protein is homologous to the site-specific DNA recombinases. Hybridization of a 3.6 kilobase EcoRI fragment carrying the spoIVC cisA gene with the EcoRI-restricted chromosomal DNA prepared from cells of various stages showed that DNA rearrangement occurs only in the mother cell in the region adjacent to spoIVC cisA 3 h after the initiation of sporulation. This result coincides with that of Stragier et al. (P. Stragier, B. Kunkel, L. Kroos, and R. Losick, Science 243:507 512, 1989). The timing of the DNA rearrangement coincides very well with the timing of spoIVC cisA gene expression. The DNA rearrangement was not observed in spoIVC cisA mutants. These results strongly suggest that the spoIVC cisA gene encodes a site-specific DNA recombinase having a very important role in sporulation. PMID- 2105294 TI - Methyl transfer in chemotaxis toward sugars by Bacillus subtilis. AB - Like amino acids, the sugars glucose and the nonmetabolizable 2-deoxyglucose caused a turnover of methyl groups on the methyl-accepting chemotaxis proteins. These sugars also caused methanol formation on addition. Thus, in contrast to chemotaxis in Escherichia coli, taxis to phosphotransferase sugars by Bacillus subtilis utilizes the methyl-accepting chemotaxis proteins. PMID- 2105295 TI - Genetic mapping of the structural gene for phospholipase C of Pseudomonas aeruginosa PAO. AB - An insertion mutation constructed by gene replacement methods was used to map the gene corresponding to the hemolytic phospholipase C (plcS gene) in Pseudomonas aeruginosa PAO1 by R68.45-mediated conjugation. plcS mapped approximately at 67 min on the 75-min chromosomal map (B. W. Holloway, K. O'Hoy, and H. Matsumoto, p. 213-221, in S. J. O'Brien, ed., Genetic Maps 1987, vol. 4, 1987), between the markers pur-67 and pru-375 and considerably distal to the regulatory genes plcA and plcB, which are located at approximately 12 min. PMID- 2105296 TI - Methanogenesis involving a novel carrier of C1 compounds in Methanogenium tationis. AB - The pathway of CO2 reduction to methane in Methanogenium tationis and Methanogenium thermophilicum is similar to that observed in other methanogens. In M. tationis a novel pterin, tatiopterin, is present. This pterin appears to be a structural and functional analog of methanopterin and sarcinapterin. Folate could not substitute for tatiopterin. PMID- 2105297 TI - Pseudomonas putida KF715 bphABCD operon encoding biphenyl and polychlorinated biphenyl degradation: cloning, analysis, and expression in soil bacteria. AB - We cloned the entire bphABCD genes encoding degradation of biphenyl and polychlorinated biphenyls to benzoate and chlorobenzoates from the chromosomal DNA of Pseudomonas putida KF715. The nucleotide sequence revealed two open reading frames corresponding to the bphC gene encoding 2,3-dihydroxybiphenyl dioxygenase and the bphD gene encoding 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (ring-meta-cleavage compound) hydrolase. PMID- 2105298 TI - Expression of the Pseudomonas aeruginosa toxA positive regulatory gene (regA) in Escherichia coli. AB - The regA gene is a positive regulatory gene that regulates toxin A production in Pseudomonas aeruginosa at the transcriptional level. The product of the regA gene was examined in Escherichia coli with the expression vector pT7-7. A 1.3-kilobase AvaI-HindIII fragment containing the regA gene was cloned into the pT7-7 vector. A recombinant plasmid (pAH1) encoded a 29-kilodalton protein. The molecular weight of this protein correlated closely with the predicted molecular weight of the RegA protein. Production of the RegA protein in E. coli required both an E. coli promoter and an E. coli ribosome-binding site. Two in-frame deletion derivatives in which certain regions of the regA gene were expressed from the T7 promoter encoded 26- and 18-kilodalton fusion proteins, respectively. The RegA protein and the two fusion proteins were localized to the inner membrane of E. coli. Neither RegA protein nor the two fusion proteins showed DNA-binding activity to the 410-base-pair fragment containing the upstream region of toxA when synthesized in E. coli. PMID- 2105299 TI - A simple and sensitive in vivo luciferase assay for tRNA-mediated nonsense suppression. AB - We present a rapid assay for tRNA suppression in living Escherichia coli. An amber, ochre, or opal nonsense mutation in a cloned luxB gene from the bacterium Vibrio harveyi was suppressed. Because luciferase (Lux) activity depends completely on the appearance of the full-length luxB gene product, the amount of light produced was proportional to tRNA-mediated nonsense suppression in the cell. This luminometric assay was notably quicker, easier, and more sensitive than a traditional colorimetric assay employing beta-galactosidase. Assays required only one addition to a growing culture and were complete within 1 min. Light output was directly proportional to the amount of bacterial luciferase in a sample over a range of greater than or equal to 40,000-fold. Fewer than 100 cells were required for detection of Lux with ordinary instrumentation; assays were 80 fold more sensitive than simultaneous beta-galactosidase measurements. Assayed cells survived and could be recovered as colony formers. The beta-galactosidase colorimetric assay and the luciferase assay were similarly reproducible. Light from colonies expressing Lux was visible to the dark-adapted eye and useful for screening. A rapid assay that does not depend on the formation of permanent transformants can be based on electroporation followed by luminometry. PMID- 2105300 TI - Negative regulator of sigma G-controlled gene expression in stationary-phase Bacillus subtilis. AB - In some media, Bacillus subtilis can maintain a prolonged stationary growth phase; however, in other media, nutrient depletion triggers a complex differentiation that culminates in production of a dormant endospore. This differentiation requires the expression of many genes. We found that during the stationary phase in media in which the cells do not form endospores and do not normally express these sporulation-essential genes, a recessive mutation in spoIIAB caused increased transcription of a set of genes essential for sporulation. Evidently, the wild-type product of spoIIAB acts during the stationary phase to prevent expression of additional sporulation-specific genes. PMID- 2105301 TI - Evidence for two structural genes for alkaline phosphatase in Bacillus subtilis. AB - Two secreted alkaline phosphatase proteins were purified from cultures of Bacillus subtilis JH646MS. The two proteins showed slight differences in subunit molecular weight, substrate specificity, and charge characteristics. A total of 62% of the first 22 amino-terminal amino acids were identical. Both sequences showed conservation of structural features identified in Escherichia coli and human alkaline phosphatases. One alkaline phosphatase was a monomer and the other was a dimer. Southern analysis of genomic DNA with degenerative oligomers based on the amino acid sequences suggest that there are two structural genes for alkaline phosphatase in the genome of B. subtilis. PMID- 2105302 TI - Modification of dinitrogenase reductase in the cyanobacterium Anabaena variabilis due to C starvation and ammonia. AB - In the heterocystous cyanobacterium Anabaena variabilis, a change in nitrogenase activity and concomitant modification of dinitrogenase reductase (the Fe protein of nitrogenase) was induced either by NH4Cl at pH 10 (S. Reich and P. Boger, FEMS Microbiol. Lett. 58:81-86, 1989) or by cessation of C supply resulting from darkness, CO2 limitation, or inhibition of photosystem II activity. Modification induced by both C limitation and NH4Cl was efficiently prevented by anaerobic conditions. Under air, endogenously stored glycogen and added fructose protected against modification triggered by C limitation but not by NH4Cl. With stored glycogen present, dark modification took place after inhibition of respiration by KCN. Reactivation of inactivated nitrogenase and concomitant demodification of dinitrogenase reductase occurred after restoration of diazotrophic growth conditions. In previously C-limited cultures, reactivation was also observed in the dark after addition of fructose (heterotrophic growth) and under anaerobiosis upon reillumination in the presence of a photosynthesis inhibitor. The results indicate that modification of dinitrogenase reductase develops as a result of decreased carbohydrate-supported reductant supply of the heterocysts caused by C limitation or by increased diversion of carbohydrates towards ammonia assimilation. Apparently, a product of N assimilation such as glutamine is not necessary for modification. The increase of oxygen concentration in the heterocysts is a plausible consequence of all treatments causing Fe protein modification. PMID- 2105303 TI - A plasmid vector with a selectable marker for halophilic archaebacteria. AB - A mutant resistant to the gyrase inhibitor novobiocin was selected from a halophilic archaebacterium belonging to the genus Haloferax. Chromosomal DNA from this mutant was able to transform wild-type cells to novobiocin resistance, and these transformants formed visible colonies in 3 to 4 days on selective plates. The resistance gene was isolated on a 6.7-kilobase DNA KpnI fragment, which was inserted into a cryptic multicopy plasmid (pHK2) derived from the same host strain. The recombinant plasmid transformed wild-type cells at a high efficiency (greater than 10(6)/micrograms), was stably maintained, and could readily be reisolated from transformants. It could also transform Halobacterium volcanii and appears to be a useful system for genetic analysis in halophilic archaebacteria. PMID- 2105304 TI - In vitro interactions of CysB protein with the cysJIH promoter of Salmonella typhimurium: inhibitory effects of sulfide. AB - The cysteine regulon of Salmonella typhimurium is positively regulated by the CysB protein and an inducer, which can be either O-acetyl-L-serine or N-acetyl-L serine. In vivo experiments confirmed that sulfide and L-cysteine (supplied as L cystine) interfere with induction by exogenously supplied O-acetyl-L-serine and also showed the same effects when N-acetyl-L-serine was used as an inducer. In a gel shift assay, purified CysB protein bound specifically to a 278-base-pair DNA fragment containing the S. typhimurium cysJIH promoter region. Binding occurred in the absence of inducer but did not stimulate in vitro transcription initiation, indicating that binding alone is insufficient to cause formation of a transcription initiation complex. Addition of N-acetyl-L-serine or O-acetyl-L serine was required for transcription initiation and also stimulated binding three- to eightfold. Sulfide inhibited both transcription initiation and binding by interfering with the stimulatory effects of inducer in a competitive manner. These findings indicate that sulfide is an anti-inducer and may explain why full expression of the cysteine regulon requires sulfur limitation. L-Cysteine did not affect in vitro transcription initiation or binding of CysB protein to the cysJIH promoter region. The in vivo effects of L-cysteine may be secondary to its degradation to sulfide by the inducible enzyme cysteine desulfhydrase. PMID- 2105305 TI - A target for carbon source-dependent negative regulation of the citB promoter of Bacillus subtilis. AB - Expression of the aconitase (citB) gene of Bacillus subtilis is subject to catabolite repression in cells grown in minimal media. In nutrient broth medium, citB expression is low in growing cells but is induced when cells enter sporulation. A 600-base-pair DNA fragment that extends from positions -400 through +200, relative to the transcription start site, was shown to include all of the cis-acting sequences necessary for catabolite repression and sporulation associated regulation. This was demonstrated by fusing this DNA fragment to the Escherichia coli lacZ gene, integrating the fusion in the amyE locus of the B. subtilis chromosome, and measuring the regulation of expression of beta galactosidase. By creating a series of deletions from either end of the 600-base pair fragment, it was possible to define a target for catabolite repression; at least part of this target lies within the sequence between positions -84 and -68. DNA fragments that included positions -84 through +36, when carried on high-copy plasmids, caused derepression of aconitase synthesis, as if a negative regulator were being titrated. The same plasmids caused derepression of citrate synthase activity as well. Deletion of the sequence between positions -84 and -67 abolished this titration effect for both enzymes. Mutations that altered the target for catabolite repression also affected the inducibility of citB at the onset of sporulation, at least when sporulation was induced by the addition of decoyinine, an inhibitor of guanine nucleotide synthesis. When sporulation was induced by exhaustion of nutrient broth, there was no detectable difference in expression of citB-lacZ fusions whether or not they had the citB sequence from positions -84 to -67, suggesting that the mechanisms of regulation of citB in minimal medium and nutrient broth are different. PMID- 2105306 TI - DNA sequences and characterization of four early genes of the tryptophan pathway in Pseudomonas aeruginosa. AB - Two pairs of related but easily distinguishable genes for the two subunits of anthranilate synthase have been identified in Pseudomonas aeruginosa. These were cloned, sequenced, inactivated in vitro by insertion of an antibiotic resistance cassette, and returned to the P. aeruginosa chromosome, replacing the wild-type gene. Gene replacement implicated only one of the pairs in tryptophan biosynthesis. This report describes the cloning and sequencing of the tryptophan related gene pair, designated trpE and trpG, and presents experiments implicating their gene products in tryptophan production. DNA sequence analysis as well as growth and enzyme assays of insertionally inactivated strains indicated that trpG is the first gene in a three-gene operon that also includes trpD and trpC. Complementation of Trp auxotrophs by R-prime plasmids (T. Shinomiya, S. Shiga, and M. Kageyama, Mol. Gen. Genet., 189:382-389, 1983) has shown that a large cluster of pyocin R2 genes is flanked at one end by trpE and the other end by trpDC; the physical map that was obtained shows the distance between trpE and trpDC to be about 25 kilobases. Our restriction map of the trpE and trpGDC regions agrees with data presented by Shinomiya et al. PMID- 2105308 TI - Bupropion dosing recommendations. PMID- 2105309 TI - Waldenstrom's macroglobulinemia. PMID- 2105307 TI - Nucleotide sequence and further characterization of the Synechococcus sp. strain PCC 7002 recA gene: complementation of a cyanobacterial recA mutation by the Escherichia coli recA gene. AB - The nucleotide sequence and transcript initiation site of the Synechococcus sp. strain PCC 7002 recA gene have been determined. The deduced amino acid sequence of the RecA protein of this cyanobacterium is 56% identical and 73% similar to the Escherichia coli RecA protein. Northern (RNA) blot analysis indicates that the Synechococcus strain PCC 7002 recA gene is transcribed as a monocistronic transcript 1,200 bases in length. The 5' endpoint of the recA mRNA was mapped by primer extension by using synthetic oligonucleotides of 17 and 27 nucleotides as primers. The nucleotide sequence 5' to the mapped endpoint contained sequence motifs bearing a striking resemblance to the heat shock (sigma 32-specific) promoters of E. coli but did not contain sequences similar to the E. coli SOS operator recognized by the LexA repressor. An insertion mutation introduced into the recA locus of Synechococcus strain PCC 7002 via homologous recombination resulted in the formation of diploids carrying both mutant and wild-type recA alleles. A variety of growth regimens and transformation procedures failed to produce a recA Synechococcus strain PCC 7002 mutant. However, introduction into these diploid cells of the E. coli recA gene in trans on a biphasic shuttle vector resulted in segregation of the cyanobacterial recA alleles, indicating that the E. coli recA gene was able to provide a function required for growth of recA Synechococcus strain PCC 7002 cells. This interpretation is supported by the observation that the E. coli recA gene is maintained in these cells when antibiotic selection for the shuttle vector is removed. PMID- 2105310 TI - Characterization of an interaction between protein C and ceruloplasmin. AB - Coagulation factors V and VIII are substrates for activated protein C. Binding sites for the protease have been localized to homologous sequences within the terminal A domains of these proteins. Since ceruloplasmin contains significant sequence homology to these domains, a study was undertaken to determine whether ceruloplasmin was an activated protein C-binding protein. Ceruloplasmin was observed to inhibit the activated protein C-catalyzed inactivation of both factor Va and factor VIII. Searches of the ceruloplasmin sequence revealed a decapeptide sequence, HAGMETTYTV (residues 1028-1037) that shares 60 and 40% sequence identity with the activated protein C binding sequence in factors VIII and V, respectively. This peptide also inhibited factor Va inactivation and in addition was observed to enhance the amidolytic activity of activated protein C. The ferrous oxidase activity of ceruloplasmin was stimulated 5-fold by activated protein C, and this effect was negated by the peptide HAGMETTYTV. These results indicate that these conserved sequences of ceruloplasmin and factors V and VIII interact with activated protein C and suggest that this region may be important in the regulation of this anticoagulant protein. PMID- 2105311 TI - The structure of (xylose)2glucose-O-serine 53 found in the first epidermal growth factor-like domain of bovine blood clotting factor IX. AB - We reported the presence of a new trisaccharide composed of two xylose and reducing terminal glucose residues linked to serine residues of bovine blood clotting factors VII and IX (Hase, S., Kawabata, S., Nishimura, H., Takeya, H., Sueyoshi, T., Miyata, T., Iwanaga, S., Takao, T., Shimonishi, Y., and Ikenaka, T. (1988) J. Biochem. (Tokyo) 104, 867-868). The present paper describes the detailed structural analysis of the trisaccharide. Glycopeptides were prepared from bovine factor IX by digestion with Pronase followed by purification by column chromatography. The trisaccharide was released from the protein by the beta-elimination reaction with hydrazine, and the reducing end of the sugar chain was tagged with 2-aminopyridine. The fluorescent pyridylamino derivative of the trisaccharide was purified by gel filtration and reversed-phase high performance liquid chromatography. The glycopeptides and pyridylamino-trisaccharide thus obtained were subjected to methylation study, 500-MHz 1H nuclear magnetic resonance spectroscopy, and periodate oxidation. Glucose and xylose belong to the D series by high performance liquid chromatography on a chiral column. From the results, the structure of the trisaccharide is proposed as: D-Xyl p alpha 1-3-D Xyl p alpha 1-3-D-Glcp beta 1-O-Ser-53. PMID- 2105312 TI - Evidence for a juvenile hormone receptor involved in protein synthesis in Drosophila melanogaster. AB - The larval fat body of newly eclosed adults of Drosophila melanogaster was found to contain a single major binding protein specific for juvenile hormone (JH). Binding to this protein was saturable, of high affinity, and specific for JH III. The protein has a subunit molecular weight (Mr) of 85,000, as determined by photoaffinity labeling. The same or similar JH-binding protein was found in larval fat body and cuticle of third instar larvae and in male accessory glands and heads of newly eclosed adults. It was not found in several other tissues in adults. Male accessory gland cytosol from wild-type flies was found to contain a single binder with a dissociation constant (KD) of 6.7 nM for JH III; a binder in similar preparations from the methoprene-tolerant (Met) mutant had a KD value 6 fold higher. JH III stimulated protein synthesis in glands cultured in vitro, but this effect was reduced in Met flies as compared to wild-type flies, establishing a correlation between JH binding and biological activity of the hormone. In addition, glandular protein accumulation during the first 2 days of adult development was less in Met flies than in wild-type flies. These results strongly suggest that the binding protein we have identified mediates this JH effect in male accessory glands and thus is acting as a JH receptor. PMID- 2105313 TI - Methyl group turnover on methyl-accepting chemotaxis proteins during chemotaxis by Bacillus subtilis. AB - The addition of attractant to Bacillus subtilis briefly exposed to radioactive methionine causes an increase of labeling of the methyl-accepting chemotaxis proteins. The addition of attractant to cells radiolabeled for longer times shows no change in the extent of methylation. Therefore, the increase in labeling for the briefly labeled cells is due to an increased turnover of methyl groups caused by attractant. All amino acids gave enhanced turnover. This turnover lasted for a prolonged time, probably spanning the period of smooth swimming caused by the attractant addition. Repellent did not affect the turnover when added alone or simultaneously with attractant. Thus, for amino acid attractants, the turnover is probably the excitatory signal, which is seen to extend long into or throughout the adaptation period, not just at the start of it. PMID- 2105314 TI - The route of Ca2+ entry during reloading of the intracellular Ca2+ pool in pancreatic acini. AB - To trace the route of Ca2+ entry and the role of the cytosolic Ca2+ pool in reloading of the internal stores of pancreatic acinar cells, Mn2+ influx into Fura 2-loaded cells and the effect of 1,2-bis(2-aminophenoxyethane-N,N,N',N' tetraacetic acid (BAPTA) on Ca2+ storage in intracellular stores and reloading were examined. Treatment of acini suspended in Ca2(+)-free medium with carbachol (cell stimulation) or carbachol and atropine (reloading period) resulted in 2 fold increase in the rate of Mn2+ influx. Increasing Ca2+ permeability of the plasma membrane by elevation of extracellular pH from 7.4 to 8.2 further increased the rate of Mn2+ influx observed during cell stimulation and the reloading period. Loading the acini with BAPTA by incubation with 50 microM of the acetomethoxy form of BAPTA (BAPTA/AM) was followed by a transient reduction in free cytosolic Ca2+ concentration ((Ca2+]i). To compensate for the increased Ca2+ buffering capacity in the cytosol the acini incorporated Ca2+ from the external medium. Although BAPTA prevented changes in free cytosolic Ca2+ concentration during carbachol and atropine treatment, it had no apparent effect on Ca2+ content of the internal stores or the ability of agonists to release Ca2+ from these stores. Loading the cytosol with BAPTA considerably reduced the rate of Ca2+ reloading. These observations are not compatible with direct communication between the medium and the inositol 1,4,5-trisphosphate releasable pool and provide direct evidence for Ca2+ entry into the cytosol prior to its uptake into the intracellular pool, both during cell stimulation and the Ca2+ reloading. PMID- 2105315 TI - The structure of the TATA-less rat tissue-type plasminogen activator gene. Species-specific sequence divergences in the promoter predict differences in regulation of gene expression. AB - The genomic region carrying the rat tissue-type plasminogen activator (tPA) gene including its 5'-flanking sequence has been isolated and characterized by restriction enzyme analysis, Southern blotting, and DNA sequencing of all coding parts and the promoter region. The gene is approximately 25 kilobase pairs in size and comprises 14 exons separated by 13 introns. All the exon/intron boundaries agree with the GT-AG rule. The organization of the rat tPA gene is very similar to its human counterpart, and the location of the introns in the protein structure is identical to the human tPA gene. To characterize the promoter region, the transcription initiation site was identified by S1 nuclease protection experiments. A DNA fragment carrying 621 nucleotides of the 5' flanking sequence was found to confer basal promoter activity and hormone responsiveness to a reporter gene construct in primary cultures of rat granulosa cells. Analysis of the rat tPA promoter sequence and a comparison with the human and mouse counterparts reveal several species-specific differences: the rat and mouse tPA promoters lack typical TATA and CAAT sequences found in the human tPA gene. Furthermore, the rat tPA promoter contains a consensus cAMP-responsive element shown to be required for cAMP responsiveness in eucaryotic genes. At the same position as the cAMP-responsive element in the rat gene, the mouse and human tPA genes have a 12-O-tetradecanoylphorbol-13-acetate-responsive element known to mediate activation by phorbol esters. The differences in the promoter sequences of the rat, mouse, and human tPA genes may have implications for the regulation of the tPA gene in different species. PMID- 2105316 TI - Identification of lysine 15 at the active site in Escherichia coli glycogen synthase. Conservation of Lys-X-Gly-Gly sequence in the bacterial and mammalian enzymes. AB - Glycogen synthases from Escherichia coli and mammalian muscle differ in many respects including regulation, sugar nucleotide specificity, and primary sequence. To compare the structure of the active sites in these enzymes, the affinity-labeling study of the E. coli enzyme was carried out using adenosine diphosphopyridoxal as the reagent. The E. coli enzyme was inactivated in a time- and dose-dependent manner when incubated with the reagent followed by sodium borohydride reduction. The inactivation was markedly protected by ADP-glucose and ADP, suggesting that the reagent was bound to the substrate-binding site. The stoichiometry of the bound reagent to the enzyme was approximately 1:1. Sequence analysis of the labeled peptide isolated from a proteolytic digest of the modified protein revealed that Lys15 is labeled. Based on the geometry of the reagent, the epsilon-amino group of this residue might be located close to the pyrophosphate moiety of ADP-glucose bound to the E. coli enzyme, like that of Lys38 in the rabbit muscle enzyme, which is labeled by uridine diphosphopyridoxal (Tagaya, M., Nakano, K., and Fukui, T. (1986) J. Biol. Chem. 260, 6670-6676; Mahrenholz, A. M., Wang, Y., and Roach, P. J. (1988) J. Biol. Chem. 263, 10561 10567). The importance of the conserved sequence of Lys-X-Gly-Gly is discussed in connection with the glycine-rich region found in many nucleotide-binding proteins. PMID- 2105317 TI - Post-translational modification of low molecular mass GTP-binding proteins by isoprenoid. AB - Several proteins in mammalian cells are modified post-translationally by the isoprenoid, farnesol. Incubation of cultured cells with [3H]mevalonate, an isoprenoid precursor, results in the labeling of multiple polypeptides, the most prominent of which migrate in the range of 21-26 kDa on sodium dodecyl sulfate polyacrylamide gels. In Rat-6 fibroblasts transformed by H-ras, one of the farnesylated proteins was identified as p21ras by two-dimensional immunoblotting. However, this protein accounted for only a small proportion of the [3H]mevalonate derived radioactivity incorporated into 21-26-kDa proteins. Murine erythroleukemia cells, which did not express immunodetectable quantities of p21ras, contained several 21-26-kDa farnesylated proteins distributed in both the cytosolic and particulate fractions. At least eight of these proteins were capable of binding [alpha-32P]GTP on nitrocellulose membranes. Pulse-chase studies showed that the isoprenoid modification did not necessarily result in the translocation of the cytosolic proteins to the cell membrane. A prominent group of carboxyl-methylated proteins in murine erythroleukemia cells overlapped with the 21-26-kDa farnesylated proteins on one-dimensional sodium dodecyl sulfate gels. Methylation of this group of proteins was selectively abolished when cells were treated with lovastatin, an inhibitor of isoprenoid synthesis. Addition of exogenous mevalonate to the lovastatin-treated cells fully restored carboxyl methylation. These studies suggest that the 21-26-kDa farnesylated proteins in mammalian cells are members of a recently discovered family of low molecular mass GTP-binding proteins which, although ras-related, appear to be distinct structurally and possibly functionally from the products of the ras genes. The observed isoprenoid-dependent carboxyl methylation of a group of 21-26-kDa proteins suggests that the low molecular mass GTP-binding proteins may undergo a series of post-translational C-terminal cysteine modifications (i.e. farnesylation, carboxyl methylation) analogous to those recently elucidated for p21ras. PMID- 2105318 TI - Effect of nerve growth factor and fibroblast growth factor on SCG10 and c-fos expression and neurite outgrowth in protein kinase C-depleted PC12 cells. AB - The role of protein kinase C (PKC) in mediating nerve growth factor (NGF) or basic fibroblast growth factor (bFGF)-stimulated SCG10 and c-fos expression as well as neurite outgrowth was studied in PC12 cells. Activators of PKC such as phorbol 12-myristate 13-acetate (PMA) or 1-oleoyl 2-acetyl glycerol mimicked the stimulatory effect of NGF and bFGF on SCG10 mRNA levels. Induction involved a protein synthesis-dependent mechanism and was maximal within 12-24 h of exposure. Chronic treatment of the cells with PMA for up to 8 days resulted in a substantial decrease (approximately 90%) in total PKC activity in the continued presence of PMA. PKC depletion did not affect NGF- or bFGF-stimulated SCG10 mRNA induction and bFGF-stimulated c-fos mRNA induction. However, NGF-stimulated c-fos mRNA induction was attenuated. In addition, induction of neurite outgrowth was not abolished in PKC-depleted cells. The results imply that PKC is not involved in NGF- and bFGF-stimulated SCG10 mRNA induction and neurite outgrowth. Furthermore, while the effect of bFGF on c-fos mRNA induction is PKC-independent, that of NGF is mediated by PKC-dependent and -independent pathways. PMID- 2105319 TI - A block at Man5GlcNAc2-pyrophosphoryldolichol in intact but not disrupted castanospermine and swainsonine-resistant Chinese hamster ovary cells. AB - A mutation in glycoprotein processing inhibitor-resistant (PIR) Chinese hamster ovary (CHO) cells was previously shown to result in a block at the Man5GlcNAc2 stage of the dolichol-oligosaccharide biosynthetic pathway (Lehrman, M.A., and Zeng, Y. (1989) J. Biol. Chem. 264, 1584-1593). These cells had normal mannose-P dolichol synthase activity and were able to transfer the Man5GlcNAc2 oligosaccharides to protein. We have now characterized the mutation in greater detail. In PIR cells, biosynthesis of GDP-mannose and mannose-P-dolichol was normal, and pulse-chase analysis indicated that the rate of Man5GlcNAc2-P-P dolichol formation in vivo was similar to that in parental CHO cells but without subsequent formation of larger intermediates. Cell fusion studies demonstrated that the PIR genotype was recessive and that PIR cells could complement the mutation in B4-2-1 cells, which fail to synthesize mannose-P-dolichol. In contrast to the results obtained with intact cells, incubation of membrane preparations of PIR cells with GDP-[3H]mannose resulted in the synthesis of intermediates containing up to 9 mannose residues, indicating that the cells contained active mannosyltransferases VI to IX. With a simplified assay for the formation of intermediates containing 6 to 9 mannoses, it was shown that physical disruption of PIR cells was able to eliminate the block at the pentamannosyl stage. Furthermore, although the temperature requirements of the reactions for the control CHO and PIR membranes were similar, Man5GlcNAc2-elongating activity in CHO membranes was inhibited by alkaline pH treatment, whereas this treatment irreversibly stimulated the activity in PIR membranes. Taken together, these results suggest that the PIR cells have a recessive defect, and that the missing gene product is required by mannosyltransferase VI in vivo for proper utilization of either mannose-P-dolichol or Man5GlcNAc2-P-P-dolichol. Since the defect was manifested in vivo but not in vitro, this requirement appears necessary for intact cells but not for disrupted cells or isolated membranes. PMID- 2105320 TI - Purification and characterization from bovine brain cytosol of a protein that inhibits the dissociation of GDP from and the subsequent binding of GTP to smg p25A, a ras p21-like GTP-binding protein. AB - A novel regulatory protein for smg p25A, a ras p21-like GTP-binding protein, was purified to near homogeneity from bovine brain cytosol. This regulatory protein, designated here as smg p25A GDP dissociation inhibitor (GDI), inhibited the dissociation of GDP, but not of guanosine 5'-(3-O-thio)triphosphate (GTPgamma S), from smg p25A. smg p25A GDI also inhibited the binding of GTPgamma S to the GDP bound form of smg p25A but not of that to the guanine nucleotide-free form. GDI did not stimulate the GTPase activity of smg p25A and by itself showed neither GTPgammaS-binding nor GTPase activity. GDI was inactive for other ras p21/ras p21 like GTP-binding proteins including c-Ha-ras p21, rhoB p20, and smg p21. The Mr value of GDI was estimated to be about 54,000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis, about 65,000 from the S value (4.5 S), and about 82,000 by gel filtration. The isoelectric point of GDI was about pH 5.6. The activities of GDI were killed by tryptic digestion or heat boiling. These results indicate that bovine brain cytosol contains a regulatory protein for smg p25A that inhibits the dissociation of GDP from and thereby the subsequent binding of GTP to this protein. PMID- 2105321 TI - Gz, a guanine nucleotide-binding protein with unique biochemical properties. AB - Cloning of a complementary DNA (cDNA) for Gz alpha, a newly appreciated member of the family of guanine nucleotide-binding regulatory proteins (G proteins), has allowed preparation of specific antisera to identify the protein in tissues and to assay it during purification from bovine brain. Additionally, expression of the cDNA in Escherichia coli has resulted in the production and purification of the recombinant protein. Purification of Gz from bovine brain is tedious, and only small quantities of protein have been obtained. The protein copurifies with the beta gamma subunit complex common to other G proteins; another 26-kDa GTP binding protein is also present in these preparations. The purified protein could not serve as a substrate for NAD-dependent ADP-ribosylation catalyzed by either pertussis toxin or cholera toxin. Purification of recombinant Gz alpha (rGz alpha) from E. coli is simple, and quantities of homogeneous protein sufficient for biochemical analysis are obtained. Purified rGz alpha has several properties that distinguish it from other G protein alpha subunit polypeptides. These include a very slow rate of guanine nucleotide exchange (k = 0.02 min-1), which is reduced greater than 20-fold in the presence of mM concentrations of Mg2+. In addition, the rate of the intrinsic GTPase activity of Gz alpha is extremely slow. The hydrolysis rate (kcat) for rGz alpha at 30 degrees C is 0.05 min-1, or 200-fold slower than that determined for other G protein alpha subunits. rGz alpha can interact with bovine brain beta gamma but does not serve as a substrate for ADP-ribosylation catalyzed by either pertussis toxin or cholera toxin. These studies suggest that Gz may play a role in signal transduction pathways that are mechanistically distinct from those controlled by the other members of the G protein family. PMID- 2105322 TI - Toxic injury from mercuric chloride in rat hepatocytes. AB - The relationship between cytosolic free Ca2+, mitochondrial membrane potential, ATP depletion, pyridine nucleotide fluorescence, cell surface blebbing, and cell death was evaluated in rat hepatocytes exposed to HgCl2. In cell suspensions, 50 microM HgCl2 oxidized pyridine nucleotides between 1/2 and 2 min, caused ATP depletion between 2 and 5 min, and produced an 89% loss of cell viability after 20 min. Rates of cell killing were identical in high (1.2 mM) and low (2.6 microM) Ca2+ buffers. Cytosolic free Ca2+ was determined in 1-day cultured hepatocytes by ratio imaging of Fura-2 employing multiparameter digitized video microscopy. In high Ca2+ medium, HgCl2 caused a 3-4-fold increase of free Ca2+ beginning after 6-7 min, but free Ca2+ did not change in low Ca2+ medium. Bleb formation occurred after about 4-5 min in both buffers prior to any increase of free Ca2+. Subsequently, in high Ca2+ medium, blebs became hot spots of free Ca2+ (greater than 600 nM). After about 2 min of exposure to HgCl2, rhodamine 123 fluorescence redistributed from mitochondrial to cytosolic compartments signifying collapse of the mitochondrial membrane potential. The results taken together demonstrate that bleb formation, ATP depletion, and the onset of cell death are not dependent on an increase of cytosolic free Ca2+. HgCl2 toxicity appears to be a consequence of inhibition of oxidative phosphorylation leading to ATP depletion and cell death. PMID- 2105323 TI - Attitudes towards contraceptive implants and injectables among present and former users in Singapore. AB - In a comparison of present and past users of contraceptive implants (Norplant) or injectables (DMPA) and discontinuers of Norplant or DMPA, information concerning the women's knowledge and perception of, and attitude to, implants and injectable contraceptives, was studied. The long duration of action (5 years) of implants was perceived positively by all groups as compared to the shorter 3-month duration of injectables, though this was seen as an advantage over the pill. It appears that the Norplant system has potential for wider use in Singapore in the future. PMID- 2105324 TI - Cell surface galactosyltransferase mediates the initiation of neurite outgrowth from PC12 cells on laminin. AB - Neurite outgrowth from PC12 pheochromocytoma cells, as well as from peripheral and central nervous system neurons in vitro, is mediated by the extracellular matrix molecule, laminin. We have recently shown that mesenchymal cell spreading and migration on laminin is mediated, in part, by the cell surface enzyme, beta 1,4 galactosyltransferase (GalTase). GalTase is localized on lamellipodia of migrating cells where it functions as a laminin receptor by binding to specific N linked oligosaccharides in laminin (Runyan et al., 1988; Eckstein and Shur, 1989). In the present study, we examined whether GalTase functions similarly during neutrite outgrowth on laminin using biochemical and immunological analyses. PC12 neurite outgrowth was inhibited by reagents that perturb cell surface GalTase activity, including anti-GalTase IgG and Fab fragments, as well as the GalTase modifier protein alpha-lactalbumin. Control reagents had no effect on neurite outgrowth. Furthermore, blocking GalTase substrates on laminin matrices by earlier galactosyltion or enzymatic removal of GalTase substrates also inhibited neurite outgrowth. Conversely, neurite outgrowth was enhanced by the addition of UDP-galactose, which completes the GalTase enzymatic reaction, while inappropriate sugar nucleotides had no effect. The effects of all these treatments were dose and/or time dependent. Surface GalTase was shown to function during both neurite initiation and elongation, although the effects of GalTase perturbation were most striking during the initiation stages of neurite formation. Consistent with this, surface GalTase was localized by indirect immunofluorescence to the growth cone and developing neurite. Collectively, these results demonstrate that GalTase mediates the initiation of neurite outgrowth on laminin, and to a lesser extent, neurite elongation. Furthermore, this study demonstrates that process extension from both mesenchymal cells and neuronal cells is partly dependent upon specific oligosaccharide residues in laminin. PMID- 2105325 TI - Thrombin-induced prostacyclin biosynthesis in human endothelium: role of guanine nucleotide regulatory proteins in stimulus/coupling responses. AB - The regulation of prostacyclin (PGI2) synthesis by cultured human umbilical vein endothelium (HUVEC) was investigated. HUVEC monolayer generation of PGI2 was monitored by RIA of 6-keto PGF1 alpha and dose-dependent increases observed with human alpha- and gamma-thrombins, histamine, or arachidonate. Alpha thrombin (10 nM) produced levels of 6-keto PGF1 alpha approximating responses with 1 microM gamma-thrombin, 5 microM arachidonate, or 10 microM histamine. Diisopropyl phosphorofluoridate-inactivated alpha-thrombin did not stimulate PGI2 release, demonstrating that catalytic activity was required for thrombin-stimulated PGI2 release. Sodium fluoride (NaF), at concentrations known to activate guanine nucleotide regulatory proteins (G proteins), directly stimulated HUVEC PGI2 synthesis in a dose-dependent and time-dependent manner (20 mM NaF, 4.4 +/- 0.5 fold increase at 10 min, 11.9 +/- 1.5-fold increase at 30 min). Neither alpha thrombin nor NaF-stimulated PGI2 release was dependent upon the availability of extracellular Ca++). The hypothesis that G proteins are involved in agonist stimulated PGI2 synthesis was further supported by studies using digitonin permeabilized HUVEC monolayers challenged with another G protein activator, guanosine 5'-0-3-thiotrisphosphate (GTP gamma S), which effected significant dose dependent increases in PGI2 synthesis compared with control levels of 6-keto PGF1 alpha. In contrast, the G-protein inhibitor GDP beta S, (guanosine 5'-0-2 thiodiphosphate), attenuated alpha-thrombin-mediated prostaglandin generation. Treatment of HUVEC monolayers with pertussis toxin (1 microgram/ml) did not inhibit the PGI2 synthesis stimulated by either alpha-thrombin, NaF, or histamine but catalyzed the ADP ribosylation of a 40 kDa membrane protein which cross reacted with antisera against a synthetic peptide corresponding to an amino acid sequence common to the alpha-subunit of other G-proteins. Preincubation of HUVEC microsomal membranes with alpha-thrombin diminished pertussis toxin-catalyzed ADP ribosylation in a time-dependent manner. These data suggest that thrombin stimulation of PGI2 synthesis by HUVEC monolayers requires the catalytically functional enzyme and further suggests that the thrombin-occupied receptor is coupled to phospholipase activities by a pertussis toxin-insensitive guanine nucleotide regulatory protein in human endothelial cell membranes. PMID- 2105326 TI - Growth-inhibiting effect of tumor necrosis factor on human umbilical vein endothelial cells is enhanced with advancing age in vitro. AB - We have examined the effects of in vitro aging on the growth capacity of human umbilical vein endothelial cells (HUVECs) under the influence of tumor necrosis factor (TNF) with or without interferon-gamma (IFN-gamma). The growth and colony forming abilities of control cells were impaired with advancing age in vitro, especially at later stages (more than 70-80% of life span completed). It was found that treatment with TNF inhibited growth and colony-forming efficiency at any in vitro age. The effects of TNF were shown to increase with increasing in vitro age, as reflected by a more pronounced increase in doubling times, a decrease in saturation density, and a reduction in colony-forming efficiency. However, the characteristics of TNF receptors, including the dissociation constant, and the number of TNF-binding sites per cell-surface area remained rather constant. The effect of TNF was augmented by IFN-gamma at a dose that alone affected growth and colony formation only slightly. The augmentation by IFN gamma was also found to depend on in vitro age; the synergy with TNF in the deterioration of colony-forming ability was observed only in "aged" cells. These results suggest that the intrinsic responsiveness of HUVECs to growth-inhibiting factors, as well as to growth-stimulating factors, changes during aging in vitro. PMID- 2105327 TI - Cortical spreading depression is associated with arachidonic acid accumulation and preservation of energy charge. AB - The present study aimed to study the relation between the release of arachidonic acid (AA) and the energy state in cerebral cortices of rats during single episodes of cortical spreading depression (CSD). The changes in concentrations of AA, labile phosphate compounds [ATP, ADP, AMP, and phosphocreatine (PCr)], and glycolytic metabolites (lactate, pyruvate, glucose, and glycogen) were studied during and following the large change of the local direct current (DC) potential. Free AA increased markedly during the DC shift, continued to increase during the subsequent 3 min, and returned to control levels at 4-5 min after CSD. PCr decreased by 38% in the first minutes following the DC shift, while ADP increased by 38%. Both returned to normal within a few minutes. ATP, AMP, and energy charge remained constant throughout the experimental period. Glucose decreased by 47% and glycogen by 34% for a few minutes following CSD, while lactate increased by 105% at 2-3 min and by 77% at 4-5 min after CSD. The metabolites returned to control levels at 10 min after CSD. Considering the constant energy charge at all time points during CSD, it is suggested that the AA rise reflects augmented phospholipase activity due to either increased intracellular [Ca2+] or receptor stimulation or both. The possibility that N-methyl-D-aspartate receptors play a role in the release of AA, and that free AA in turn could be part of the mechanism of CSD, is discussed. PMID- 2105328 TI - Effect of enhancement of endogenous cholinergic tone with pyridostigmine on the dose-response relationships of growth hormone (GH)-releasing hormone-induced GH secretion in normal subjects. AB - It is well known that GH responses to GH-releasing hormone (GHRH) show marked interindividual variations in normal subjects, which have been attributed to a variable somatostatinergic tone. Recently, it has been shown that enhancement of cholinergic tone with the acetylcholinesterase inhibitor pyridostigmine (PD), which presumably acts by inhibiting somatostatin release, stimulates basal GH secretion and GH responses to a maximal dose of GHRH. In this study we have investigated the effects of PD on the dose-response relationships of GHRH-induced GH secretion in normal subjects. Our data showed that PD (120 mg, orally, at-60 min) induced a clear-cut increase in basal GH levels, significantly different from that after saline treatment, at 15, 30, 45, 60, 90, and 120 min. Moreover, PD administration markedly potentiated GH responses to GHRH at doses of 500, 100, 25, 10, and 3 micrograms/subject, as assessed by either area under the curve or maximal peak GH levels. In fact, GH responses to pyridostigmine plus 3 micrograms GHRH were similar to those to the administration of 500 and 100 micrograms GHRH alone. Our findings of marked increases in GH response to GHRH after pyridostigmine administration show that with enhancement of cholinergic tone, the dose of GHRH needed to induce a similar increase in GH is reduced 30 times. PMID- 2105329 TI - Differential regulation of luteinizing hormone, follicle-stimulating hormone, and free alpha-subunit secretion from the gonadotrope by gonadotropin-releasing hormone (GnRH): evidence from the use of two GnRH antagonists. AB - To examine the differential regulation of glycoprotein hormone secretion from the gonadotrope by GnRH, the Nal-Glu GnRH antagonist was administered to euthyroid women in the early follicular phase (days 1-5) of the menstrual cycle, and the results compared to previous studies with the Nal-Arg GnRH antagonist. After a 4 h period of baseline sampling at a frequency of every 10 min, a single sc dose of the GnRH antagonist was administered to each subject. Frequent sampling continued for 8 h, followed by hourly sampling for a further 16 h. LH, FSH, and free alpha subunit were measured serially in assays with high specificity. There was a 90% concordance of LH and free alpha-subunit pulses during the baseline sampling period. Pulsatile secretion of LH and free alpha-subunit was immediately abolished at the highest dose of the Nal-Glu antagonist for at least 8 h. The maximum percent suppression of LH after administration of the Nal-Glu GnRH antagonist was 70 +/- 4%, 80 +/- 4%, and 83 +/- 1% at doses of 15, 50, and 150 micrograms/kg, respectively, compared to 51 +/- 10%, 70 +/- 5%, and 69 +/- 5% at doses of 50, 150, and 500 micrograms/kg Nal-Arg antagonist. Decreases in FSH were 28 +/- 2%, 32 +/- 7%, and 39 +/- 2%, with increasing doses of the Nal-Glu antagonist compared with 25 +/- 6%, 17 +/- 6%, and 28 +/- 4% reductions at increasing doses of the Nal-Arg antagonist. Free alpha-subunit decreased 22 +/- 4%, 23 +/- 4%, and 28 +/- 3% at increasing doses of the Nal-Glu antagonist and 12 +/- 4%, 27 +/- 4%, and 30 +/- 7% with increasing doses of the Nal-Arg antagonist. For the Nal-Glu antagonist, suppression of LH was greater than that of FSH and free alpha-subunit at all doses (P less than 0.001), while FSH suppression was greater than that of free alpha-subunit at the highest dose only (P less than 0.05). For the Nal-Arg antagonist, LH suppression was greater than that of FSH or free alpha-subunit at all doses (P greater than 0.01), and FSH suppression exceeded that of free alpha-subunit at the 50 micrograms/kg dose. Suppression of LH was greater with the Nal-Glu antagonist than with the Nal-Arg antagonist at doses of 50 and 150 micrograms/kg (P less than 0.05), and FSH suppression was greater with the Nal-Glu antagonist at 150 micrograms/kg (P less than 0.01), while the degrees of maximum suppression were similar for the two different GnRH antagonists for free alpha-subunit.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2105330 TI - Effects of transdermal 17 beta-estradiol treatment and naloxone infusion on gonadotropin response to gonadotropin-releasing hormone in postmenopausal women. AB - Estrogens exert both inhibitory and stimulatory effects on the secretion of GnRH and gonadotropins in women. The endogenous opioid peptides seem to mediate, at least in part, the inhibitory action exerted by estrogens on LH secretion. However, the mechanisms that mediate the stimulatory effect of estrogens on LH secretion are still unclear. The present study was performed to evaluate whether the endogenous opioid peptides could also participate in the stimulatory effect that estrogens exert on the gonadotropin response to GnRH. In postmenopausal women, a GnRH test was performed both under basal conditions and during the second month of treatment with transdermal 17 beta-estradiol (E2). In untreated postmenopausal women, two different doses of naloxone infusion failed to modify the LH and FSH responses to GnRH stimulation. During treatment with transdermal E2, the LH response to GnRH was significantly increased, while the FSH response was similar to that before treatment. Naloxone completely counteracted the enhanced LH response to GnRH observed during E2 treatment. On the other hand, naloxone did not significantly modify the FSH response to GnRH. The present results confirm that E2 exerts a sensitizing effect on the pituitary LH response to GnRH and suggest that the endogenous opioid system could be involved in this effect. PMID- 2105331 TI - Patterns of pulsatile pituitary glycoprotein secretion in central hypothyroidism and hypogonadism. AB - Five patients with central hypothyroidism and hypogonadism due to mass or infiltrative lesions of the pituitary and hypothalamus were studied to determine pulsatile pituitary glycoprotein secretion patterns. Blood samples were obtained every 15 min over 24 h, and TSH, LH and FSH were measured by immunoradiometric assays. Hormone pulses were located by cluster analysis, and pulse patterns were compared to those in normal subjects. Three patients had unmeasurable LH levels, while two had a normal number of low amplitude pulses. In contrast, all patients had normal FSH pulse frequency, and only one had low pulse amplitude. Three patients had normal 24-h TSH pulse frequency and amplitude, while two had slightly decreased pulse parameters. However, all failed to show normal nocturnal increases in TSH pulse amplitude. Thus, anatomical hypothalamic-pituitary lesions disrupt pulsatile glycoprotein secretion in a discordant fashion. LH is most severely affected, with abnormal pulse patterns similar to those in idiopathic central hypogonadism. FSH and TSH pulses are relatively preserved, but loss of the usual nocturnal increase in TSH pulse amplitude is sufficient to cause clinical hypothyroidism. Whether these defects reflect intrinsic pituitary disease or impaired hypothalamic releasing factor function remains to be determined. PMID- 2105332 TI - Physiological regulation of circadian and pulsatile thyrotropin secretion in normal man and woman. AB - The circadian and pulsatile TSH secretion profiles were investigated in 5 females at the time of menstruation and 21 healthy males by sampling blood every 10 min for 24 h. Computer-assisted analysis, i.e. the Cluster and Desade programs, revealed means of 9.9 +/- 1.7 (Cluster) and 11.4 +/- 3.9 (Desade) pulses/24 h. More than 50% of the TSH pulses were detected between 2000-0400 h. Male and female subjects showed no significant difference in the basal mean and pulsatile secretion of TSH or in the TSH response to TRH (200 micrograms). Repetition of the TSH secretion analysis in 4 healthy subjects after 1, 2, and 6 months (2 subjects) revealed a significantly better cross-correlation within than between individuals (P less than 0.0001). We modulate the circadian TSH secretion pattern by acute sleep withdrawal or prolonged sleep after a night of sleep withdrawal in six healthy male volunteers. Sleep withdrawal augmented the nightly TSH secretion (mean serum TSH, 2.1 +/- 1.3 mU/L; mean TSH in sleep, 1.3 +/- 0.5 mU/L; P less than 0.05), whereas sleep after sleep withdrawal almost completely suppressed the circadian variation (mean TSH, 1.1 +/- 0.7 mU/L; P less than 0.01). This modulation is due to a significant decrease in pulse amplitude, but not to an alteration in the frequency or temporal distribution of TSH pulses. PMID- 2105333 TI - Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. AB - A new immunochemiluminometric TSH assay (ICMA) was shown to offer improved analytical (+2 SD of zero) and functional (20% interassay coefficient of variation) sensitivity [0.003 vs 0.045 +/- 0.005 (+/- SE; range, 0.01-0.07); 0.018 vs. 0.23 +/- 0.02 (range, 0.10-0.35, mU/L); analytical vs. functional sensitivity limit for the ICMA vs. 10 other TSH immunometric assays, respectively]. The ICMA was used to study the physiological relationship between serum TSH and free T4 [as reflected by free T4 index (FT4I)] values at both steady state and 14 days after acute pharmacological T4 administration (3 mg oral T4 load plus 0.3 mg daily). At steady state, an inverse log/linear relationship was found between serum TSH and FT4I values (log TSH = 2.56 - 0.022 FT4I; r = 0.84; P less than 0.001). Ten to 14 days after acute T4 suppression in 5 euthyroid subjects, serum TSH/FT4I levels had plateaued after decreasing in parallel to the slope of the steady state relationship, suggesting that the degree of T4 suppression of TSH can be predicted from an individual's pituitary TSH/free T4 set-point and the magnitude of the serum T4 elevation achieved. Ambulatory and hospitalized patient sera, previously identified as having low (less than 0.1 mU/L) TSH levels by a less sensitive assay, were restudied by the TSH ICMA. Normal TSH values ranged from 0.39-4.6 mU/L, whereas the majority of hyperthyroid patients [52 of 54 (96% ambulatory) and 22 of 23 (96%, hospitalized)] had undetectable (less than 0.005 mU/L), basal TSH levels and absent TRH stimulated TSH responses. In contrast, most (32 of 37; 86%) of hospitalized nonhyperthyroid patients with low (less than 0.1 mU/L) TSH values due to nonthyroidal illness or glucocorticoid treatment had detectable (greater than 0.01 mU/L) basal and TRH stimulated TSH levels. The positive relationship between basal and TRH-stimulated TSH levels was shown to extend down to the detectability limit of the assay (0.005 mU/L), which further supported the authenticity of the subnormal TSH ICMA measurements. The new TSH ICMA is considered to represent the first of a third generation of clinical TSH assays, since it has a functional (interassay) sensitivity that is 2 orders of magnitude greater than that of typical first generation TSH RIAs and 1 order of magnitude greater than current second generation TSH immunometric methods. Such third generation TSH assays will facilitate both the optimization of T4 therapy as well as the diagnosis of hyperthyroidism in hospitalized patients with nonthyroidal illness. PMID- 2105334 TI - Primary cortisol resistance presenting as isosexual precocity. AB - Primary cortisol resistance (PCR) is a rare cause of hypercortisolism and usually does not produce clinical manifestations. This report describes primary cortisol resistance in a boy with isosexual precocity. A 6 7/12-yr-old boy had Tanner stage 3 pubic hair, accelerated linear growth, and advanced bone age (10 yr), but normal (for age) tests. There were no features of glucocorticoid excess. Serum androstenedione and dehydroepiandrosterone concentrations were 4.7 +/- 0.3 nmol/L (mean +/- SEM of four measurements; normal less than 1.2) and 13.5 nmol/L (single measurement; normal, 1.0-2.2), respectively. The serum testosterone concentration was 0.9 nmol/L (normal, less than 0.7), and FSH and LH were normal. Serum cortisol concentrations were 1590 +/- 110 nmol/L (normal, 190-630) and 580 +/- 60 nmol/L (normal, 50-410) at 0800 and 2000 h, respectively. Serum cortisol responded normally to insulin-induced hypoglycemia. Glucocorticoids and adrenal androgens were resistant to suppression by dexamethasone. The Kd of [3H]dexamethasone binding to the glucocorticoid receptors of mononuclear leukocytes was increased (6.4 +/- 0.8 nM; mean +/- SEM of four determinations; normal, 1.4-3.4; P less than 0.001), but the binding capacity was normal. This patient with isosexual precocity has PCR, as indicated by functionally abnormal glucocorticoid receptors and hypercortisolism without other clinical or biochemical manifestations of Cushing's syndrome. Excessive adrenal stimulation by ACTH caused increased secretion of both cortisol and adrenal androgens, and the latter caused the clinical manifestations. PCR should be considered in other male children with isosexual precocity or female children with heterosexual precocity. PMID- 2105335 TI - Evaluation of Bacto TB hydrolysis reagent (Tween 80) for the identification of Branhamella catarrhalis. AB - An investigation of the hydrolysis of Tween 80 reagent by Branhamella catarrhalis and related organisms (Neisseria and Moraxella species) revealed that only B. catarrhalis gave a positive result. A total of 226 strains, including reference organisms and clinical isolates, were studied. B. catarrhalis changed the color of the reagent from amber to pink-red after overnight incubation. We recommend this simple and cost-effective test as an alternative procedure to DNase testing or tributyrin hydrolysis or as a supplemental procedure for the identification of B. catarrhalis in clinical specimens. PMID- 2105337 TI - Pseudarthrosis of the radius associated with neurofibromatosis: report of a case and review of the literature. AB - An 11-year-old child with pseudarthrosis of the radius associated with neurofibromatosis was treated by conventional bone graft. Five years after the operation, the pseudarthrosis united, but the grafted bone was slightly sclerotic and bowed. This article describes the clinical findings and postoperative results, and discusses the current surgical approaches in the treatment of pseudarthrosis of the radius. PMID- 2105336 TI - Evaluation of an enzyme-linked immunosorbent assay that uses ferrous metal beads for determination of antihistoplasmal immunoglobulins G and M. AB - A rapid enzyme-linked immunosorbent assay (ELISA) for the detection of human class-specific antibodies to Histoplasma capsulatum (histoplasmal immunoglobulin M [HIgM] and histoplasmal IgG [HIgG]) was developed by using antigen adsorbed onto polycarbonate-coated ferrous beads. In the ELISA method all the reagents used were commercially available. In 135 specimens from patients with confirmed histoplasmosis, sensitivities were 76% for complement fixation (CF), 53% for immunodiffusion (ID), and 64% for the ELISA for HIgM and HIgG combined. The ELISA detected histoplasmal antibody in 36% of the specimens with negative antibody titers by CF and 46% of the specimens with negative antibody titers by ID. The ELISA detected histoplasmal antibody in 27% of specimens that were negative by both CF and ID. When limited to specimens collected within 4 months of the onset of histoplasmosis symptoms, sensitivities were 82% for CF, 63% for ID, and 86% for ELISA for HIgG and HIgM combined. Within this group, ELISA detected histoplasmal antibody in 90% of the specimens that were negative by CF, 76% that were negative by ID, and 100% that were negative by both CF and ID. The specificity of the ELISA could not be fully addressed since sera from patients with other fungal infections were not available. PMID- 2105338 TI - Lateral tethering of the proximal femoral physis complicating the treatment of congenital hip dysplasia. AB - One hundred forty-two consecutive patients treated at the Portland Shriners Hospital from 1975 through 1984 for congenital hip dysplasia were reviewed. Fourteen patients (10%) with 18 lateral physeal tethers were identified; three tethers occurred in the uninvolved hip. The lateral bridge was apparent at an average of 8 years. Age at initial treatment averaged 10 months and, at follow up, 10 years. Fourteen of the tethers occurred in the treated hip, five after open reductions, and seven after closed reductions. Lateral physeal tethering is an iatrogenic entity. Knowledge of this condition should lead to early recognition and prevention of the secondary deformities. PMID- 2105339 TI - Transcriptional and posttranscriptional regulation of macrophage-specific colony stimulating factor gene expression by tumor necrosis factor. Involvement of arachidonic acid metabolites. AB - The effects of tumor necrosis factor (TNF) on the regulation of macrophage specific colony stimulating factor (CSF-1) gene expression have been studied in HL-60 cells during monocytic differentiation. CSF-1 transcripts were undetectable in uninduced HL-60 cells, reached maximal levels by 3 h of exposure to TNF, and returned to that of control cells by 24 h. Transcriptional run-on analysis demonstrated that exposure to TNF stimulated the rate of CSF-1 gene transcription by 6.4-fold. The combination of a protein synthesis inhibitor, cycloheximide, and TNF increased levels of CSF-1 mRNA compared with treatment by TNF alone. We also studied the signal transduction mechanisms responsible for regulating TNF-induced CSF-1 mRNA levels. Both 4-bromophenacyl bromide and quinacrine, inhibitors of phospholipase A2 activity, blocked TNF-induced increases in CSF-1 transcripts in a concentration-dependent manner, while caffeic acid and nordihydroguaiaretic acid, inhibitors of the 5-lipoxygenase pathway, had no detectable effect on induction of CSF-1 RNA. PGE2 or dibutyryl cAMP treatment of HL-60 cells in the presence of TNF blocked the expression of CSF-1 mRNA in a dose-dependent manner. These findings suggest that the increase in CSF-1 RNA observed during TNF treatment is regulated, at least in part, by both transcriptional and posttranscriptional mechanisms, and that PGE2 and cAMP regulate transcriptional activation of the CSF-1 gene by TNF. PMID- 2105340 TI - Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro. AB - Bisphosphonates are useful in treatment of disorders with increased osteoclastic activity, but the mechanism by which bisphosphonates act is unknown. We used cultures of chicken osteoclasts to address this issue, and found that 1 hydroxyethylidenediphosphonic acid (EHDP), dichloromethylidenediphosphonic acid (Cl2MDP), or 3-amino-1-hydroxypropylidene-1,1-diphosphonic acid (APD) all cause direct dose-dependent suppression of osteoclastic activity. Effects are mediated by bone-bound drugs, with 50% reduction of bone degradation occurring at 500 nM to 5 microM of the different agents. Osteoclastic bone-binding capacity decreased by 30-40% after 72 h of bisphosphonate treatment, despite maintenance of cell viability. Significant inhibition of bone resorption in each case is seen only after 24-72 h of treatment. Osteoclast activity depends on ATP-dependent proton transport. Using acridine orange as an indicator, we found that EHDP reduces proton accumulation by osteoclasts. However, inside-out plasma membrane vesicles from osteoclasts transport H+ normally in response to ATP in high concentrations of EHDP, Cl2MDP, or APD. This suggests that the bisphosphonates act as metabolic inhibitors. Bisphosphonates reduce osteoclastic protein synthesis, supporting this hypothesis. Furthermore, [3H]leucine incorporation by the fibroblast, which does not resorb bone, is also diminished by EHDP, Cl2MDP and APD except when co cultured with bisphosphonate-binding bone particles. Thus, the resorption antagonizing capacities of EHDP, Cl2MDP and APD reflect metabolic inhibition, with selectivity for the osteoclast resulting from high affinity binding to bone mineral. PMID- 2105342 TI - Loss of cerebrovascular autoregulation in experimental meningitis in rabbits. AB - The present study was designed to determine whether cerebrovascular autoregulation is intact in experimental meningitis and to examine the relationship between fluctuations in cerebral blood flow (CBF) and increased intracranial pressure (ICP). Measurements of CBF were determined by the radionuclide microsphere technique in rabbits with experimental Streptococcus pneumoniae meningitis with simultaneous ICP monitoring via an implanted epidural catheter. CBF and ICP measurements were determined at baseline and when mean arterial blood pressure (MABP) was artificially manipulated by either pharmacologic or mechanical means. CBF was pressure passive with MABP through a range of 30-120 torr, and ICP directly correlated with CBF. These findings indicate that autoregulation of the cerebral circulation is lost during bacterial meningitis, resulting in a critical dependency of cerebral perfusion on systemic blood pressure, and that the parallel changes in ICP and in CBF suggest that fluctuations in CBF may influence intracranial hypertension in this disease. PMID- 2105341 TI - Intracellular glucose oxidation and glycogen synthase activity are reduced in non insulin-dependent (type II) diabetes independent of impaired glucose uptake. AB - To examine whether reduced rates of oxidative (Gox) and non-oxidative (Nox) glucose metabolism in non-insulin-dependent diabetes mellitus (NIDDM) are due to reduced glucose uptake, intrinsic defects in intracellular glucose metabolism or increased fat oxidation (Fox), indirect calorimetry was performed at similar glucose uptake rates in eight nonobese NIDDM and eight comparable nondiabetic subjects. Three glucose clamp studies were performed: one in the nondiabetic and two in the NIDDM subjects. In the nondiabetic subjects, glucose uptake was increased to 7.62 +/- 0.62 mg/kg of fat-free mass (FFM) per min by increasing serum insulin to 309 pmol/liter at a glucose concentration of 5.1 mmol/liter. By raising the concentration of either serum glucose or insulin fourfold in the NIDDM subjects, glucose uptake was matched to nondiabetic subjects (8.62 +/- 0.49 and 8.59 +/- 0.51 mg/kg FFM per min, respectively, P = NS). Skeletal muscle glycogen synthase activity and plasma lactate levels were measured to characterize Nox. When glucose uptake was matched to nondiabetics by hyperglycemia or hyperinsulinemia, Gox was reduced by 26-28% in NIDDM (P less than 0.025) whereas Fox was similar. Nox was greater in NIDDM (P less than 0.01) and was accompanied by increases in circulating lactate levels. Glycogen synthase activity was reduced by 41% (P less than 0.025) when glucose uptake was matched by hyperglycemia. Glycogen synthase activity was normalized in NIDDM, however, when glucose uptake was matched by hyperinsulinemia. Therefore, a defect in Gox exists in nonobese NIDDM subjects which cannot be overcome by increasing glucose uptake or insulin. Since both glucose uptake and Fox were similar in the two subject groups these factors were not responsible for reduced Gox. Increased Nox in NIDDM is primarily into lactate. Reduced glycogen synthase activity in NIDDM is independent of glucose uptake but can be overcome by increasing the insulin concentration. PMID- 2105343 TI - Marked synergism between tumor necrosis factor-alpha and interferon-gamma in regulation of keratinocyte-derived adhesion molecules and chemotactic factors. AB - T lymphocytes and mononuclear cells preferentially accumulate in the epidermis in inflammatory skin disease. To determine the role of keratinocytes in both the chemotaxis and adhesion of these cells to the epidermis, cultured keratinocytes were incubated with IFN-gamma and tumor necrosis factor-alpha (TNF-alpha), and mRNA detected and quantitated for IL-8, monocyte chemotaxis and activating factor, and intercellular adhesion molecule-1. Whereas induction of these mRNAs was either absent, or relatively weak and transient, to either IFN-gamma or TNF alpha alone, when administered in combination there was a dramatic increase and persistence in the induction of all three genes. Pretreatment of the keratinocytes with cycloheximide failed to eliminate transcription, implying that all three are primary response genes. Transforming growth factor-beta, which modulates other keratinocyte functions (not related to adhesion or chemotaxis of inflammatory cells) failed to induce any of the genes. These novel findings potentially explain the selective recruitment of T cells and monocytes observed in inflammatory skin disease, because IFN-gamma and TNF-alpha can co-ordinately regulate keratinocyte-derived chemoattractants and adhesion molecule production. PMID- 2105344 TI - Birthdates of the growth hormone releasing factor cells of the rat hypothalamus: an autoradiographic study of immunocytochemically identified neurons. AB - Growth hormone releasing factor (GRF) neurons in the arcuate nucleus of the hypothalamus and somatostatin (SRIF) neurons in the anterior periventricular region of the hypothalamus act to control the release of growth hormone from the anterior pituitary. To investigate the possibility that the growth-controlling functions of these cells might be compromised by injuries to the developing brain, it is important to know the details of the production and differentiation of these small, specialized cell groups. The overall pattern of cell production in the hypothalamus is known from autoradiographic studies with general nuclear stains, but no data are available on the birthdates (times of final mitoses) of GRF-producing cells. The present study was undertaken to determine when the GRF cells form. Counts of immunocytochemically identified GRF cells labeled on given days were taken from serial coronal sections through the hypothalamus of adult rats labeled on the 10th-17th days of gestation (day of finding a vaginal plug = day 1). As has been shown for the hypothalamus in general, the GRF cells showed a gradient of production from anterior to posterior. The peak of anterior cell proliferation was on day 13, middle cells on day 14, and posterior cells on day 15. These dates are 1 or 2 days earlier than those of GRF-negative cells in the same regions. No lateral to medial gradient of formation was seen in GRF cells. Rather, the laterally placed cells along the base of the brain and those surrounding the ventromedial nucleus formed simultaneously with the GRF cells of the arcuate nucleus. The birthdating results presented here are in agreement with the results of studies of teratogens which suggest that rat postnatal growth is reduced most severely by exposure to neurotoxic agents on days 12 or 13 of gestation. On the basis of data for the whole hypothalamus, such treatments would appear to be too early to interfere with cell production for the arcuate nucleus, but the timing fits the period of vulnerability as defined by the birthdates determined in the present study for the subpopulation of cells destined to produce GRF. PMID- 2105345 TI - Chronic urticaria and monoclonal IgM: treatment with ibuprofen. PMID- 2105346 TI - Placement of cast restorations over direct pulp capping procedures: a decision analytic approach. AB - A review of the literature shows a significant amount of controversy regarding the success of pulp capping procedures, with the average clinically evaluated pulp capping success being 81%, and 75% when evaluated histologically. This study evaluated the costs and benefits of a pulp cap versus endodontic therapy for a tooth that is to receive a cast restoration, and determined what level of success is needed for pulp capping to be the preferred treatment. PMID- 2105348 TI - The use of reservoir devices for the simultaneous delivery of two metered-dose aerosols. AB - Many patients benefit from using metered-dose inhalers (MDIs) with spacer or reservoir devices. Concomitant therapy with separate MDI doses of cromolyn sodium and a beta-agonist is common practice. If two puffs from each drug could be placed into a chamber, the patient could administer both medications at once, enhancing compliance. A multistage liquid impinger (a four-stage inertial impaction device incorporating an inlet bend and an absolute filter, which separates an aerosol cloud into six fractions) was used to investigate such a possibility. Cromolyn sodium and albuterol MDIs were used with an Aerochamber (Monaghan Medical Corp., Plattsburgh, N.Y.) and an Inspirease (Schering Corp., Kenilworth, N.J.). Results are reported by analyzing milligrams of cromolyn sodium per actuation retrieved. With the Aerochamber, two puffs of cromolyn sodium followed by two puffs of albuterol resulted in the total "dose to patient" being reduced by 75% (0.19 versus 0.05 mg) and the effective dose of fine particles (less than 6.5 microns) being reduced by 80% (0.13 versus 0.03 mg) compared to two puffs of cromolyn sodium alone. With the Inspirease, total dose was decreased by 80% (0.32 versus 0.06 mg), whereas the effective dose of fine particles was reduced by 60% (0.19 versus 0.05 mg) compared to one puff of cromolyn sodium alone. The use of cromolyn sodium and albuterol MDIs in a multipuff combination with the Aerochamber or the Inspirease is not recommended because this leads to a loss of the dose delivered compared to a single administration. PMID- 2105347 TI - Cardiac effects of carbon dioxide-consuming and carbon dioxide-generating buffers during cardiopulmonary resuscitation. AB - Recent studies have demonstrated an increase in carbon dioxide (CO2) tension (PCO2) in both mixed venous and coronary vein blood early in the course of cardiac arrest and cardiopulmonary resuscitation. Because increased PCO2 in the myocardium correlates with both ischemic injury and depression of contractile function, the effects of hypertonic solutions of either the CO2-"generating" sodium bicarbonate (NaHCO3) buffer, a mixture of sodium carbonate (Na2CO3) and sodium bicarbonate (carbicarb) acting as a CO2-"consuming" buffer, or saline placebo (NaCl) were compared during cardiopulmonary resuscitation in 25 healthy minipigs. Both buffer agents significantly increased the pH and HCO3- of arterial, mixed venous and coronary vein blood. Bicarbonate increased whereas carbicarb reduced blood PCO2 in the systemic circuit as anticipated. However, neither the PCO2 nor the lactate content of coronary vein blood was favorably altered by buffer therapy. Four of eight animals treated with bicarbonate, five of eight treated with carbicarb and six of nine placebo-treated animals were successfully resuscitated and had a comparable 24 h survival rate. Coronary perfusion pressure during precordial compression, a critical determinant of resuscitability, was transiently decreased by each of the hypertonic solutions. Accordingly, neither CO2-generating nor CO2-consuming buffers mitigated increases in coronary vein PCO2 or improved the outcome of cardiopulmonary resuscitation under these experimental conditions. PMID- 2105349 TI - Public-private solution to protection against the cost of long-term care. AB - The demographics of our population and our current reliance on Medicaid with a means test that no one likes suggest the need for revising our financing of long term care. Given that persons with Alzheimer's disease and related dementias are a substantial proportion of those needing long-term care, support for research to cure or control these problems should be part of a strategy for addressing the problem of long-term care. However, even if substantial progress is made there is still a need for revising our method of financing long-term care. However, other pressing societal needs, such as reducing the 2 trillion dollar federal debt, addressing the needs of the growing number of children in poverty, and caring for the more than 30 million uninsured Americans, limit the role of the federal government in financing long-term care. A proposal to provide coverage for those with functional disabilities or cognitive impairment who need chronic home care and for the initial portion of nursing home stays within a social insurance program is outlined. More extensive coverage for nursing home stays would be provided for those with community-dwelling spouses. Major financing would be provided through either a payroll tax or by a federal income tax for all age groups with supplementation from estate taxes or capital gains taxes at death. Improvement of benefits in the Medicaid program and an important role for private insurance in protecting the estates of those who become permanent nursing home residents are also suggested. PMID- 2105350 TI - Working in long-term care. PMID- 2105351 TI - The use of mupirocin in controlling methicillin-resistant Staphylococcus aureus. PMID- 2105352 TI - Staphylococcus aureus nasal colonization in a nursing home: eradication with mupirocin. AB - Recent reports have emphasized an increase in both infection and colonization with methicillin-resistant Staphylococcus aureus (MRSA) in institutionalized older patients. We studied whether or not local treatment with mupirocin ointment could eliminate nasal colonization with S aureus. A total of 102 patients in a Veterans Administration nursing home were screened for S aureus nasal colonization. Thirty-nine patients (38.2%) were colonized, 18 with methicillin sensitive Saureus (MSSA) and 21 with MRSA. Almost half of all colonized patients were in the most dependent functional category and there was a significant association of MRSA colonization, but not MSSA colonization, with poor functional status. Colonized patients were treated with mupirocin ointment applied to the anterior nares twice daily for seven days. After treatment, MSSA persisted in only two patients and MRSA in only one patient; thus, nasal colonization was eliminated in 91.4% of colonized patients. At one month and two months follow-up, 11 patients became transiently recolonized and three became persistently recolonized with S aureus. Mupirocin was well tolerated with no side effects noted. Mupirocin ointment may be useful in controlling nasal colonization with S aureus in the nursing home setting. PMID- 2105354 TI - Hepatitis B immunoprophylaxis: developing a cost-effective program in the hospital setting. PMID- 2105353 TI - Nosocomial outbreak of systemic candidosis associated with parenteral nutrition. AB - Eight patients in two surgical units developed systemic candidosis during a 40 day period from June 5 to July 13, 1987 (in five cases Candida albicans was identified). Three of them died. All cases belonged to a group of 27 patients receiving parenteral nutrition (PN), while among the 108 patients who did not receive PN, no cases were observed (p = .000001). Candida was cultured from two PN bags administered to the cases. A specialized nutrition nurse was responsible for the PN compounding and for maintaining administration sets in the two wards involved. An epidemiological investigation, in which 19 uninfected patients who had had PN were used as controls, showed no significant difference between cases and controls except that lipids were more frequently added to bags administered to cases (p = .0005). Furthermore, the bags administered to cases contained a higher average number of multidose constituents (p = .0008) when the comparison was focused on the two days before the onset of symptoms. Given the favorable medium provided by lipids, even a low level contamination of PN solutions during compounding and/or administration could have been responsible for the exposure of cases to multidose vials suggests, although not conclusively, that an extrinsic contamination occurred during compounding. Six isolates of C albicans were available from four cases. C albicans was cultured from the pharyngeal swabs of two physicians and three nurses, including the specialized nutrition nurse. PMID- 2105355 TI - Fine structure and sporogonic development of a Vavraia sp. (Microsporida: Pleistophoridae) in the biting midge Culicoides edeni (Diptera: Ceratopogonidae). AB - A microsporidium with ultrastructural characteristics of the genus Vavraia was found in the fat body of an adult specimen of Culicoides edeni (Diptera: Ceratopogonidae) collected in northern Florida. The sporogonial stages developed within sporophorous vesicles, which contained variable numbers of oval spores at maturity. The wall of the sporophorous vesicle was composed of two electron-dense outer layers and an electron-lucent intermediate layer. Sporonts contained haplokaryotic nuclei and divided by rosette formation. Mature spores had anisofilar polar filaments and measured 3.8 +/- 0.28 microns in length and 2.2 +/ 0.16 microns in width in thick sections of resin-embedded material. This is the first report of a Vavraia sp. from a species of Culicodes. PMID- 2105356 TI - Developmental time and mortality of the reduviid bug Triatoma infestans with differential exposure to coprophagic infections with Blastocrithidia triatomae (Trypanosomatidae). AB - Developmental time and survival in larvae of the reduviid bug Triatoma infestans were studied in uninfected groups and in those exposed to a coprophagic infection with Blastocrithidia triatomae. Addition to young uninfected larvae of (a) different numbers of infected bugs, (b) infected and uninfected bugs, and (c) fresh or dry infectious feces were compared. Retardation of development was evident in groups given infected larvae or fresh feces. Mortality rates were correlated with infection rates and were higher in groups given more infected bugs, independent of the presence of uninfected bugs. Therefore, bugs did not discriminate between feces from infected and uninfected bugs, or they did not reject infectious feces. Dry feces had to be redissolved with fresh feces before infection was possible. PMID- 2105357 TI - Lectin binding to cells of Schistosoma mansoni sporocysts and surrounding Biomphalaria glabrata tissue. AB - The binding of different lectins to the surface of mother and daughter sporocysts of Schistosoma mansoni (Trematoda) and to cells of its intermediate host Biomphalaria glabrata (Gastropoda) was investigated. The test system consisted of several biotin-labeled lectins, an avidin-biotin-peroxidase complex and 3,3' diaminobenzidine. The fixatives used were Formalin, Bouin's and Zenker's solutions; unfixed material was also studied. Most lectins reacted equally with host tissue and parasite tissue. However, receptors for Ulex europaeus I (most probably fucose) were only demonstrated on daughter sporocysts. Thus, a method was found to specifically mark Schistosoma mansoni daughter sporocysts in the digestive gland tissue of its intermediate host. Mother sporocysts and surrounding host tissue differed in their distribution of galactosyl groups. Both lack fucose and N-acetyl-galactosamine. The differences in lectin binding of galactosyl determinants were also observed during the in vitro development of mother to daughter sporocysts. PMID- 2105358 TI - Inhibition of benzoyl peroxide-mediated tumor promotion in 7,12 dimethylbenz(a)anthracene-initiated skin of Sencar mice by antioxidants nordihydroguaiaretic acid and diallyl sulfide. AB - Benzoyl peroxide (BPO), a free radical generating compound, is widely used in topical medications prescribed for acne vulgaris and in cosmetic products. It has been shown to possess tumor-promoting activity in murine skin initiated with chemical carcinogens such as 7,12-dimethylbenz(a)anthracene (DMBA). In the present study we assessed the effect of the antioxidants nordihydroguaiaretic acid (NDGA) and diallyl sulfide (DAS) against BPO-mediated tumor promotion in murine skin. Pretreatment of Sencar mice with NDGA and DAS prior to skin application of BPO resulted in a time- and dose-dependent inhibition of epidermal ODC induction caused by BPO. Tumor initiation was achieved by a single topical application of DMBA (10 micrograms/animal) to Sencar mice. Ten days later tumor promotion was begun by twice-weekly topical application of BPO (20 mg/animal). The anticarcinogenic effects of NDGA (25 mumol/mouse) and DAS (20 mumol/mouse) were evaluated by administering these agents topically 60 min prior to each BPO application. After 26 weeks on test, the number of benign papillomas/mouse were 0.10 +/- 0.07 and 2.15 +/- 0.30 in the NDGA and DAS pretreated group of animals as compared to 4.40 +/- 1.14 in animals receiving BPO alone. After 51 weeks on test, the number of squamous cell carcinomas/mouse were 0.00 +/- 0.00, 0.35 +/- 0.10 in the NDGA and DAS pretreated group of animals as compared to 0.65 +/- 0.12 in animals receiving BPO alone. From these data we suggest that the antioxidants NDGA and DAS can abrogate the tumor-promoting effects of BPO in murine skin and that NDGA is substantially more effective than DAS in this regard. PMID- 2105359 TI - Diagnosis of astrovirus gastroenteritis by antigen detection with monoclonal antibodies. AB - An enzyme-linked immunosorbent assay (ELISA), based on monoclonal antibodies to the astrovirus group antigen, was designed for the detection of astroviruses in stools of patients with gastroenteritis. Compared to immune electron microscopy used as the standard test, the sensitivity of the astrovirus ELISA was 91% (31/34) and the specificity was 96% (54/56). All five of the known astrovirus serotypes could be detected in 16 samples on which serotyping was done. In tests on 155 stools containing other enteric viruses, including adenoviruses, rotaviruses, caliciviruses, Hawaii virus, Snow Mountain virus, and Norwalk virus (30, 20, 70, 24, 4, and 7 samples, respectively), only 3 were positive in the astrovirus ELISA. The combined specificity for all astrovirus immune electron microscopy-negative samples was 98% (206/211). The results demonstrate that the new ELISA provides a sensitive and specific means for the diagnosis of astrovirus gastroenteritis. PMID- 2105360 TI - Penicillin tolerance in Arcanobacterium haemolyticum. AB - It was previously found that Arcanobacterium haemolyticum, which can cause tonsillitis with exanthema, is not eradicated from the pharynx by administration of phenoxymethylpenicillin, despite minimum inhibitory concentration values of 0.015-1.0 micrograms/ml. Therefore, recent clinical isolates were studied for penicillin tolerance by using a disk diffusion screening test and a pour plate assay. Macrobroth dilution minimum inhibitory and bactericidal concentrations and antibiotic kill kinetics were determined for 4 isolates. Tolerance was present in 38 of 40 clinical isolates with the disk diffusion assay. With the pour plate assay all 40 isolates were tolerant, 34 of them highly tolerant. The presence of the tolerant phenotype was confirmed by macrobroth dilution assays. It is concluded that A. haemolyticum is often penicillin-tolerant, suggesting that phenoxymethylpenicillin administration would be ineffective in eradicating A. haemolyticum from the pharynx. PMID- 2105361 TI - Successful prophylaxis of experimental streptococcal endocarditis with single dose amoxicillin administered after bacterial challenge. AB - Rats with catheter-induced aortic vegetations were challenged intravenously with various inoculum sizes of tolerant Streptococcus sanguis or Streptococcus faecalis. Single-dose amoxicillin (40 mg/kg) was given intravenously either 30 min before or 30-240 min after bacterial challenge. Prophylaxis of endocarditis against both strains was successful when the inocula used for challenge were in the range of the minimum inoculum producing bacterial endocarditis in 90% of control animals (ID90) but was less effective or failed with larger inocula or when amoxicillin administration was delayed up to 240 min after bacterial challenge with S. sanguis. In a group of rats profoundly depleted of neutrophils by a rabbit anti-rat neutrophil serum given 30 min after challenge with S. faecalis at ID90, single-dose amoxicillin administered simultaneously with the antiserum was protective, indicating that neutrophils were not required for successful endocarditis prophylaxis. PMID- 2105362 TI - Nosocomial transmission of tuberculosis associated with a draining abscess. AB - Nine secondary cases of tuberculosis and 59 tuberculin skin test conversions occurred after exposure to a hospitalized patient with a large tuberculous abscess of the hip and thigh. Among 442 tuberculin-negative hospital employees, the relative risk of skin test conversion associated with recalled exposure to the patient was 14.0 (95% confidence limits, 6.8, 28.7). Four of 5 surgical suite employees who assisted with incision and debridement of the abscess had skin test conversions, as did 85% of 33 employees on a general medical floor who recalled exposure to the patient and 30% of 20 intensive care unit employees who recalled exposure. The prevalence of tuberculin reactivity in visitors and other patients on two floors also showed a strong association with exposure to the patient. A high concentration of Mycobacterium tuberculosis in the abscessed tissue, disturbance of the surface of liquid drainage from the abscess by irrigations and by the agitated behavior of the patient, and positive air pressure in the patient's room are factors that appear to have contributed to the high risk of tuberculosis transmission. PMID- 2105364 TI - [Pulsatile LH secretion and hypothalamic-pituitary function in amenorrheic women]. AB - In order to evaluate hypothalamic-pituitary function and pulsatile LH secretion in 42 amenorrheic women, blood was collected every 20 min. for 6 hrs. The mean LH pulse frequency (LH-pf) of women with a normal cycle, PCO and hyperprolactinemia was 3.4 +/- 0.5, 5.2 +/- 0.8, and 1.6 +/- 1.0/6 hrs, respectively. Hypothalamic amenorrhea (HA) with no progesterone withdrawal bleeding showed a lower frequency of LH secretion. As LH-pf in HA with progesterone withdrawal bleeding (HAI) ranged from 0 to 5/6 hrs, the HAI group was divided into 2 groups according to whether their LH-pf was less than 3.4/6 hrs (HAIa) or more (HAIb). Pituitary response to 100 micrograms of LH-RH in HAIb was much lower than in HAIa and PCO. On the other hand, in HA with LH-pf less than 3.4, LH-pf showed a significant correlation with basal LH and FSH levels and the LH increase to 100 micrograms of LH-RH, while in HA with LH-pf greater than or equal to 3.4, LH-pf had no significant correlation with them. In PCO, a high LH pulse frequency and amplitude and LH response to 100 micrograms of LH-RH were shown, but the LH increase to 100 micrograms of LH-RH was significantly reduced with the increase in LH-pf. Pituitary response to 100 micrograms of LH-RH in women with hyperprolactinemia was maintained despite low LH-pf. These results suggest that the analysis of pulsatile LH secretion is very helpful in evaluating hypothalamic pituitary function in amenorrheic women. PMID- 2105363 TI - [Effects of 5-hydroxyeicosatetraenoic acid (5-HETE) on progesterone and prostaglandin production by human corpora lutea]. AB - The present study was undertaken to assess the effects of 5 hydroxyeicosatetraenoic acid (5-HETE) on steroidogenesis and prostaglandin (PG) production in cultured luteal cells derived from human corpora lutea in the mid luteal phase. The luteal cells were cultured with 5-HETE at 10, 100, 500, or 1,000 ng/ml in the absence or presence of hCG at 100 ng/ml for 10 days. The addition of 5-HETE to the culture media did not affect growth curves of cultured luteal cells. 5-HETE significantly inhibited progesterone (P) production by cultured luteal cells in a dose-related fashion on day 2. P production stimulated by exposure to hCG was also reduced significantly in response to 5-HETE. The addition of 5-HETE did not affect estradiol production by cultured luteal cells. The production of 6-keto-PGF1 alpha by cultured luteal cells in the presence of 5 HETE was slightly but not significantly less than that observed in the absence of 5-HETE. However, 5-HETE affects neither PGF2 alpha nor PGE2 production by cultured luteal cells throughout the culture period. The present study demonstrates that 5-HETE inhibits P production in cultured luteal cells by a mechanism(s) other than through PG production. These data suggest the involvement of a lipoxygenase pathway in the synthesis of P and 6-keto-PGF1 alpha of luteal cells. PMID- 2105366 TI - Flow cytometric parameters of neutrophil function as early indicators of sepsis- or trauma-related pulmonary or cardiovascular organ failure. AB - Flow cytometric parameters of neutrophil function, such as phagocytosis and degradation of Escherichia coli, intracellular pH value, esterase activity, and cell volume, were evaluated as risk indicators for sepsis- and trauma-related pulmonary and cardiovascular organ failure in intensive care patients. Serial blood samples (n = 201) were obtained from 47 prospectively identified patients. Each patient's condition was classified daily within four categories: post traumatic (n = 22) or septic (n = 28) organ failure, transition state (n = 119), and stable organ function after recovery (n = 27). Thirty-two parameters of neutrophil function were automatically calculated for each blood sample from several flow cytometric list mode measurements of cell samples vitally stained with acridine orange for intact and denatured DNA or with 1,4-diacetoxy-2,3 dicyanobenzene for intracellular pH and esterase activity. The DNA of dead cells was simultaneously counterstained with propidium iodide. The cell biochemical parameter pattern was significantly different among samples of patients from the four clinical categories (p less than 0.05). Hyperergic phagocytosis was observed after trauma, in contrast to hypoergic phagocytosis, increased neutrophil cell volume, and elevated intracellular pH during sepsis. The clinical categories were correctly identified in 82% of the samples by automated classification with the DIAGNOS1/SPSS program system from the flow cytometrically determined cell functions. The course of the disease was correctly predicted 3 days in advance to the clinical manifestation of pulmonary or cardiovascular organ failure in 92% of the samples. The multifunctional analysis of neutrophils by flow cytometry seems of interest for early medical intervention in preseptic and preshock patients. PMID- 2105365 TI - Studies on platelet protein phosphorylation in patients with impaired responses to platelet agonists. AB - The phosphorylation responses of platelet proteins after platelet stimulation with agonists were studied in patients with clinical bleeding disorders and various types of impaired platelet functional responses. Impaired collagen induced phosphorylation, particularly of the 47 kd substrate (P47) for protein kinase C, was observed in one patient whose platelet defect appears to be an impaired initial response to weak platelet agonists but whose platelet secretory mechanism is normal. Reduced phosphorylation of a 31 kd polypeptide was also observed. The phosphorylation defect in this patient differs from that seen in another patient in whom impaired P47 and myosin light chain phosphorylation was observed but whose functional defect may be more closely related to secretion. The results provide further evidence that phosphorylation of P47 may play a role in platelet activation mechanisms preceding secretion and that abnormalities of phosphorylation of both P47 and myosin light chain may be associated with platelet functional defects in some patients with bleeding disorders. PMID- 2105367 TI - Influence of blood withdrawal and anticoagulant on clotting activity, hematologic data, and certain rheologic measurements. AB - The influence of blood withdrawal (vacuum or slow aspiration) and anticoagulants (ethylenediaminetetraacetic acid [EDTA]; heparin; citrate; a mixture of citrate, theophylline, adenosine, and dipyridamole [CTAD]; and D-phenylalanyl-L-prolyl-L arginine chloromethyl ketone [PPACK]) on clotting activity, hematologic data, and rheologic measurements (whole blood and plasma viscosity, red cell filtration in one study) were investigated. No difference was found between the two blood withdrawal techniques on the basis of the affected measurements. EDTA appeared to be the best anticoagulant with regard to blood cell preservation and showed the lowest whole blood viscosity over a wide range of shear rates (0.1 to 87.0 sec 1). PPACK was the most potent inhibitor of clotting activity as monitored by fibrinopeptide A concentration. The results suggest that EDTA is probably a reasonable choice for rheologic studies of whole blood and should be combined with PPACK when plasma properties are studied. PMID- 2105368 TI - Fate of oleate in the colon of the rat. AB - To study the fate of oleate in the colon, oleate labeled with carbon 14 was instilled into the cecum of four rats through chronically implanted cecal cannulas. Fecal recovery of 14C and 14CO2 excretion were measured over a 3-day period. A mean of only 57% +/- 6% of the dose of [14C(U)]oleate was recovered as 14C in fecal lipid. About 8% was recovered in the aqueous phase of feces and 4% was recovered as 14CO2. Occlusion of the terminal ileum did not diminish 14CO2 excretion, excluding ileal reflux with small bowel absorption. Studies in two germ-free rats showed no conversion of [14C(U)]oleate to fecal water-soluble compounds, indicating that [14C]oleate is converted into water-soluble compounds by bacterial metabolism. The metabolism of [14C]oleate to 14CO2 was also observed in germ-free rats, indicating oxidation in the colon or other host tissues. We conclude that the colonic absorption of lipid or lipid metabolites plus conversion to water-soluble fecal compounds or volatile metabolites results in a fecal fat measurement that appreciably overestimates small bowel absorption of lipid. PMID- 2105369 TI - Inhibin immunoneutralization by antibodies raised against synthetic peptide sequences of inhibin alpha subunit: effects on gonadotrophin concentrations and ovulation rate in sheep. AB - Two experiments were conducted to explore the effectiveness of synthetic peptide based vaccines for active and passive autoimmunization of sheep against inhibin. In the first experiment, adult Romney ewes (n = 20) were actively immunized against a synthetically produced peptide that corresponded to the N-terminus of the alpha-subunit of bovine inhibin (bI alpha(1-29)-Tyr30). This peptide was conjugated to tuberculin purified protein derivative (PPD) to increase its antigenic properties. Control groups comprised non-immunized (n = 10) and PPD immunized (n = 10) ewes. Primary immunization (400 micrograms conjugate/ewe) was followed by two booster immunizations (200 micrograms conjugate/ewe), given 5 and 8 weeks later. Following synchronization of oestrus using progestagen sponges, ovulation rates were assessed by laparoscopy. Weekly blood samples were taken throughout the experiment. All inhibin-immunized ewes produced antibodies which bound 125I-labelled bovine inhibin (Mr 32,000), and ovulation rate in inhibin immunized ewes (2.15 +/- 0.22; mean +/- S.E.M.) was significantly (P less than 0.01) greater than in both non-immunized (0.90 +/- 0.23) and PPD-immunized (1.20 +/- 0.13) control groups. Immunization against the peptide, but not against PPD alone, resulted in a modest rise in plasma FSH, with mean levels after the second boost being significantly (P less than 0.025) higher (22%) than those before immunization. Moreover, when blood samples were taken (2-h intervals) from randomly selected groups of control (n = 7) and inhibin-immunized (n = 7) ewes for an 84-h period following withdrawal of progestagen sponges, the mean plasma concentration of FSH during the 48 h immediately before the preovulatory LH surge was 37% greater (P less than 0.025) in immunized than in control animals. However, more frequent blood sampling (every 15 min for 12 h) during follicular and mid-luteal phases of the oestrous cycle revealed no significant differences between treatment groups in mean plasma concentrations of FSH. In addition, neither mean concentrations of LH nor the frequency and amplitude of LH episodes differed between immunized and control ewes. However, the mean response of LH to a 2 micrograms bolus of gonadotrophin-releasing hormone, given during the luteal phase, was significantly (P less than 0.05) less in immunized than in control ewes. These findings indicate that active immunization of Romney ewes against a synthetic fragment of inhibin can promote a controlled increase in ovulation rate, but this response cannot be unequivocally related to an increase in plasma levels of FSH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2105370 TI - Inhibition by staurosporine of TRH-induced refractoriness of inositol phospholipid hydrolysis in rat anterior pituitaries. AB - To clarify the mechanism(s) underlying the TRH-induced refractory state of the anterior pituitary, we evaluated rat pituitary inositol phospholipid hydrolysis in the presence of staurosporine. TRH caused a time- and dose-dependent accumulation of inositol phosphates in rat anterior pituitary slices. Pretreatment with 550 nmol TRH/l completely abolished the subsequent accumulation of inositol phosphates in response to 140 nmol TRH/l. TRH-stimulated accumulation of inositol phosphates did not occur after pretreatment with 0.2 mumol phorbol ester/l. Refractoriness of inositol phospholipid hydrolysis which was produced by pretreatment with TRH and phorbol ester was inhibited by staurosporine. The present data support the hypothesis that protein kinase C plays a profound role in TRH induction of the refractory state of inositol phospholipid hydrolysis in the anterior pituitary. PMID- 2105371 TI - Effects of acupuncture in moderate, stable angina pectoris: a controlled study. AB - In order to evaluate the effects of acupuncture in moderate, stable angina pectoris, 49 patients were randomized to either genuine or sham acupuncture. In sham acupuncture needles were inserted into points within the same spinal segment as in genuine acupuncture, but outside the Chinese meridian system. The effect was evaluated from exercise tests, anginal attack rate and nitroglycerin consumption. There were no significant differences between the effects of genuine and sham acupuncture either on exercise test variables or on subjective variables. In patients receiving genuine acupuncture there was a significant increase in exercise tolerance (median 9%) and in delay of onset to pain (median 10%). No significant changes were observed in patients receiving sham acupuncture. Within both groups there was a median reduction of 50% in anginal attack rate and nitroglycerin consumption, and there was no significant difference between the results achieved in the two groups. It is concluded that with the present design it was not possible to demonstrate any significant differences between the effect of genuine and sham acupuncture. PMID- 2105372 TI - Heparin inhibits spontaneous thrombolysis and the thrombolytic effect of both streptokinase and tissue-type plasminogen activator. An in vitro study of the dislodgement of platelet-rich thrombi formed from native blood. AB - Two in vitro models of coronary thrombolysis in man, i.e. dislodgement of thrombi formed from non-anticoagulated human blood, either by (i) shear-stress or (ii) interaction of platelets with type I collagen fibre, were studied. Heparinization (1 U/ml) of blood prior to thrombus formation by (i) strongly inhibited spontaneous dislodgement (P less than 0.0001). Heparin (1 U/ml), when added with streptokinase (SK) or tissue-type plasminogen activator (rt-PA) prior to thrombus formation, considerably delayed thrombolysis. Furthermore, thrombolysis occurred much earlier when thrombi were perfused with SK or rt-PA in native than in heparinized blood. Heparin inhibited binding of 125I-rt-PA (17%, P less than 0.02) and plasminogen (88%, P less than 0.0005) to platelets activated by ADP in citrated platelet-rich plasma. We conclude that heparin interferes with the fibrinolytic system at the surface of activated platelets. Our findings suggest that heparin administration prior to thrombolytic therapy for acute myocardial infarction should be questioned. PMID- 2105373 TI - Pravastatin therapy in primary moderate hypercholesterolaemia: changes in metabolism of apolipoprotein B-containing lipoproteins. AB - This study examined the actions of pravastatin on the metabolism of apolipoprotein B (apo B) in very low-, intermediate-, and low-density lipoproteins (VLDL, IDL, and LDL) in 10 patients with primary moderate hypercholesterolaemia. 131I-VLDL apo B was used as a tracer, and appearance of label was followed into IDL apo B and LDL apo B. Compared to placebo, pravastatin therapy reduced levels of cholesterol in total plasma. LDL, VLDL, and IDL cholesterol by 25%, 29%, 31%, and 47%, respectively. Pravastatin treatment also significantly decreased concentrations of apo B in LDL, IDL, and VLDL. The drug significantly reduced the mean production rate for VLDL apo B by 40%, and decreased production rates for LDL apo B in eight of 10 patients. In contrast, fractional catabolic rates (FCRs) were not altered significantly in any of the three lipoprotein fractions on pravastatin therapy. Further, pravastatin produced no consistent changes in LDL particle size, composition, or LDL subclass pattern. Thus pravastatin seemingly reduced input rates for all apo B-containing lipoproteins. Consistent with previous studies, this response was most likely the result of enhanced removal of nascent lipoproteins by increased activity of LDL receptors, although decreased synthesis of apo B in the liver is a possible second action. PMID- 2105374 TI - Decision and cost-effectiveness analysis. PMID- 2105375 TI - Synthesis of apolipoprotein A-1 in pig brain microvascular endothelial cells. AB - In an approach toward the identification of hitherto unknown proteins involved in the function of the blood-brain barrier, we constructed a pig brain microvessel derived cDNA library that is enriched in blood-brain barrier specific sequences by means of subtractive cloning. Sequence analysis of selected clones revealed that one of the cDNAs encoded porcine apolipoprotein (apo) A-1. The identity of apo A-1 mRNA was further confirmed by in vitro translation of RNA from brain microvascular endothelial cells and subsequent immunoprecipitation with an antibody against human apo A-1. We further investigated the expression of apo A-1 mRNA in several tissues and in endothelial cells of the pig. It is shown that cultured brain microvascular endothelial cells provide an in vitro model to study the expression and function of apo A-1 in the microvasculature of the brain. PMID- 2105376 TI - Octopamine uptake and metabolism in the insect nervous system. AB - Several insect tissues were examined for their ability to take up octopamine in the presence and absence of sodium ions. The cockroach Malpighian tubules, ovary, and ventral nerve cord showed the highest level of sodium-dependent uptake. The adult firefly lantern exhibited substantial sodium-independent uptake. Some of these tissues were also examined for their ability to metabolize octopamine by N acetylation. Measurable N-acetyltransferase activity was present in the cockroach ventral nerve cord, tobacco hornworm CNS, and firefly light organ. N-Acetylation is proposed to be the major metabolic pathway for octopamine in the cockroach (Periplaneta americana) nervous system. Several classes of compounds, including octopamine receptor agonists, tricyclic antidepressants, amphetamines, chloroethylbenzylamines, and some experimental insecticides, were tested for their ability to inhibit octopamine uptake and metabolism. The sodium-insensitive component of uptake was not inhibited by most compounds tested, but the sodium sensitive component was strongly inhibited by xylamine, N-ethyl-N-chloroethyl-o bromobenzylamine, and their aziridinium ions (60-100%). These compounds also effectively inhibited N-acetyl-transferase (IC50 values at or below 1 microM). Other good inhibitors of N-acetyltransferase included desipramine, synephrine, and an experimental insecticide, CGA 132427. Formamidine pesticides had limited effect on both processes, and neither action seems likely to be involved in their octopaminergic actions in vivo. Cocaine was unique in stimulating N acetyltransferase activity. When inhibition of sodium-sensitive uptake is compared with inhibition of N-acetyltransferase in the cockroach ventral nerve cord, two groups of inhibitors are discernible. Type 1 compounds inhibit uptake without an effect on N-acetyltransferase, whereas type 2 compounds inhibit both processes. These results suggest a functional linkage between the uptake and acetylation of octopamine. PMID- 2105377 TI - An improved HPLC-electrochemical detection method for measuring brain levels of 5 S-cysteinyldopamine, 5-S-cysteinyl-3,4-dihydroxyphenylalanine, and 5-S-cysteinyl 3,4-dihydroxyphenylacetic acid. AB - Brain levels of the 5-S-cysteinyl adducts of 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC), and dopamine were determined in several mammalian species. The low levels of the compounds and the risk of artifacts during sample preparation necessitated rather profound modifications of the assaying method. The refined method has made it possible to present more accurate data than those previously reported from this laboratory. The occurrence of low levels of the 5-S-cysteinyl adducts in dopamine-rich brain areas, but not in cerebellum, is indirect evidence of in vivo autoxidation of DOPA, DOPAC, and dopamine. The products generated during catechol autoxidation, including quinones and reduced forms of oxygen, are known to be potentially cytotoxic. PMID- 2105378 TI - Thromboxane and prostacyclin levels in fetal rabbit brain and placenta after intrauterine partial ischemic episodes. AB - The appearance of arachidonic acid (AA) oxidation products in fetal rabbit brain and placenta under normal or partial short-term ischemic episodes induced by placental blood vessel restriction was examined. Intracerebral administration of [3H]AA into close-to-term rabbit fetuses gave rise to radioactively labeled prostaglandin (PG) E2, thromboxane B2, and 6-keto-PGF1 alpha metabolites as detected by HPLC analysis. A significant increase of 20-30% of [3H]AA precursor into eicosanoids was detected in brain of fetuses after 2-h restriction. The thromboxane B2 and 6-keto-PGF1 alpha levels were determined by radioimmunoassay technique over a period of 48 h following ischemic episodes. Thromboxane B2 content in affected animals was higher by five- and twofold at 3 h over control fetal brain and placental tissue values, respectively, and remained significantly higher for 24 h. 6-Keto-PGF1 alpha levels reached a peak value that was greater by 2.5- and 1.5-fold at 6 h for the ischemic brain and placental tissue, respectively, compared with control fetuses. PGE2 levels were less affected, attaining a maximum of 1.9- and 1.1-fold in brain and placenta correspondingly. The thromboxane/prostacyclin ratio reached a maximum in the brain after approximately 3 h, while that in the placenta continued to rise even after 20 h. Persisting high levels of thromboxane are indicative of cerebral vasoconstriction and may suggest possible damaging effects. PMID- 2105380 TI - Lectin binding identifies a subpopulation of neurons in chick dorsal root ganglia. AB - We screened a variety of lectins with different sugar specificates to determine whether subpopulations of dorsal root ganglion (DRG) neurons in the chick can be distinguished by the carbohydrates they express. Of the 15 lectins tested only those that recognize N-acetylgalactosamine (galNac) residues labeled a subset of DRG neurons. For example, Dolichos biflorus (DBA) labeled a population of small diameter neurons in the dorsomedial DRG and their terminals in the dorsal horn in hatchling chicks. Staining of live neurons in vitro demonstrated that DBA was binding to the cell surface. Labeling first appeared in sensory neurons at about St.38 (E12) and in dorsal horn laminae 1 and 2 at about St.42 (E16). Fainter labeling appeared somewhat later in lamina 3, after hatching. Labeling of the tissue sections was eliminated by chloroform: methanol extraction and reduced by alpha-N-acetylgalactosaminidase digestion, but survived trypsinization. Together these results suggest that a subset of DRG neurons in the chick can be identified by the presence of a cell surface glycoconjugate, perhaps a glycolipid, containing terminal alpha-linked galNac residues. PMID- 2105379 TI - Multiple GTP-binding proteins from cholinergic synaptic vesicles. AB - Cholinergic synaptic vesicles purified from the electric organ of the marine ray, Discopyge ommata, contain 2 different size classes of GTP-binding proteins: one or more with an apparent molecular weight (MW) between 37 and 41 kDa, and 3 major and at least 2 minor proteins with MW between 20 and 29 kDa. These GTP-binding proteins were detectable using the alpha 32P-GTP overlay technique and covalent modification with bacterial toxins. The higher MW GTP-binding proteins are ADP ribosylated by pertussis toxin and 2 of the lower MW GTP-binding proteins are sensitive to botulinum toxin. PMID- 2105381 TI - Synaptic localization and neural regulation of an N-acetylgalactosaminyl transferase in skeletal muscle. AB - We have previously documented the properties of a approximately 220-kDa cell surface glycosyltransferase that transfers N-acetylgalactosamine to oligosaccharide chains (Balsamo et al., 1986b). Because N-acetylgalactosamine terminated carbohydrates are concentrated at the neuromuscular junction (Scott et al., 1988), we assayed skeletal muscle for the presence of the N acetylgalactosaminyl transferase. Using immunohistochemical methods, we found that the enzyme is localized at neuromuscular junctions on normal adult rat muscle fibers. Biochemical assays confirm that junctional areas are highly enriched in the approximately 220-kDa immunoreactive species as well as in enzyme activity associated with the approximately 220-kDa species. This restricted distribution is dependent on synaptic integrity, as the enzyme appears extrasynaptically on denervation. These results provide a plausible metabolic basis for the localization of a synapse-specific carbohydrate and demonstrate that the expression of a glycosyltransferase is regulated by synaptic interactions. PMID- 2105382 TI - Noradrenergic modulation of the masseteric reflex in behaving cats. II. Physiological studies. AB - Studies in the preceding paper demonstrated that the amplitude of the masseteric reflex in behaving cats is augmented by pharmacological manipulations that increase norepinephrine (NE) tone in the motor trigeminal nucleus (MoV) through exogenous means. The present studies examine whether such a relationship also exists under physiological conditions, i.e., whether physiological increases in NE synaptic activity are correlated with increases in the reflex amplitude. The masseteric reflex was elicited in behaving cats by electrical stimulation of the mesencephalic trigeminal nucleus (MesV) and the response recorded via electrodes permanently placed in the masseter muscle. Following baseline measures of the reflex amplitude, the reflex was gain elicited while cats were exposed to various environmental stimuli known to activate NE neurons: 15 min of 100-dB white noise, confrontation with a dog, or auditory clicks presented repetitively at various intervals prior to MesV stimulation. Presentation of the white noise or the dog significantly facilitated the reflex response for the duration of the exposure. The clicks produced reflex facilitation at 100 and 150 msec following their presentation and reflex suppression at 20 msec. Two approaches were then employed to determine whether NE mediated, at least in part, augmentation of the reflex produced by these environmental conditions. In the first, cats were given either the alpha-1-noradrenergic antagonist prazosin (5 mg/kg, i.p.) or the serotonin antagonist methysergide (0.5 mg/kg, i.p.). In all cases, prazosin blocked the reflex augmentation whereas methysergide was without effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105383 TI - Effect of fixation-resin combinations and ruthenium red on elucidating outer envelope structure and surface morphology of two methanotrophic bacteria. AB - We examined the ultrastructure of the cell envelope in Type I, Methylomonas albus (BG8), and Type II, Methylosinus trichosporium (OB3b), methane-oxidizing bacteria by using different fixatives, ruthenium red (RR) combinations and resins. We compared LR White and Spurr embedments with the following fixations: glutaraldehyde/OsO4, two glutaraldehyde-paraformaldehyde, and two different en bloc ruthenium red procedures, one utilizing OsO4 and the other with glutaraldehyde/OsO4 in sequential fixation. These fixations were also studied by scanning electron microscopy (SEM). Unfixed cells prepared by freeze etch were used for comparison. Transmission electron microscopy of BG8 embedded in LR White resin (with or without red0 preserved a layer of cup-like structures that were not seen in Spurr resin-embedded cells unless ruthenium red was used. For OB3b, the second RR method preserved beads and filaments where only "spike-like" structures were seen in all other fixations in both resins. By SEM, all fixations preserved a capsular slime layer of BG8 that was removed from some cells by both RR methods. In all SEM fixations, a bead layer was preserved in OB3b that was enhanced by RR. Filaments seen by freeze-etch and thin-section techniques were not seen in SEM. Presence or absence of particular envelope structures in these methanotrophs is dependent on the combination of fixatives and/or resins employed and is species-specific. The chemical preparation methods used resulted in enhanced understanding of the structure and composition of the cell envelope. PMID- 2105385 TI - Training patients to administer total parenteral nutrition via subcutaneous infusion ports. AB - Training in the use of subcutaneous infusion ports for home parenteral nutrition was provided to 17 adult patients and the parents of three young patients. Areas of training included accessing and disconnecting the port, caring for the port, application of sterile dressing techniques, and instruction in other home parenteral nutrition techniques (ie, pump, tubing, and solution use). Patients were required to access the port successfully on three occasions before discharge from the hospital. Twelve of the 20 patients were judged capable of independent port care. None of the patients was readmitted for training-related problems. PMID- 2105384 TI - The cost-effectiveness of three thyroid function testing strategies for suspicion of hypothyroidism in a primary care-setting. AB - OBJECTIVE: To determine the sensitivity and specificity of thyroxine (T4) and the cost-effectiveness of three testing strategies in the diagnosis of hypothyroidism in a primary care setting. DESIGN: 1) A retrospective chart review to determine sensitivity and specificity of T4 in diagnosing hypothyroidism; a cost effectiveness analysis comparing ordering an initial T4 test alone, an initial thyroid-stimulating hormone (TSH) test alone, and T4 and TSH tests together in diagnosing hypothyroidism; a sensitivity analysis was performed on critical assumptions. SETTING: Primary care adult practice of a health maintenance organization. PATIENTS: Eight hundred sixteen consecutive patients suspected of having hypothyroidism who had both T4 and TSH tests performed. INTERVENTIONS: None. RESULTS: The sensitivity of a T4 cut-off of 7 micrograms/dl (90.3 nmol/L) in diagnosing primary hypothyroidism was 93% (95% confidence interval = 85-100%) and the specificity was 68% (95% confidence interval = 65-71%). The cost effectiveness ratios of using an initial T4 or TSH test were about the same across a wide range of test characteristics and disease prevalence estimates. As the ratio of T4 to TSH test charges declines from 0.6 to 0.2, the marginal cost of the TSH-first method increases from $3,500 to $18,000 for each additional hypothyroid patient identified. Ordering both tests together was very costly compared with the single test methods ($125,000 for each additional case diagnosed) and remained so under a wide range of assumptions. CONCLUSIONS: When hypothyroidism is suspected, a TSH-first testing approach is generally preferable due to its greater sensitivity and, under most assumptions, only small increment in average or marginal cost per case compared with a T4-first method. PMID- 2105386 TI - Are obese children truly unfit? Minimizing the confounding effect of body size on the exercise response. AB - To test the hypothesis that obese children are unfit (i.e., have abnormal responses to exercise testing consistent with reduced levels of habitual physical activity), we used new analytic strategies in studies of 18 obese children performing cycle ergometry. The subject's weight (mean +/- SD) was 168 +/- 24% that predicted by height, and the age range was 9 to 17 years. Size-independent measures of exercise (e.g., the ratio of oxygen uptake (VO2) to work rate during progressive exercise and the temporal response of VO2, carbon dioxide output (VCO2), and minute ventilation (VE) at the onset of exercise) were used. The ability to perform external mechanical work was corrected for VO2 at unloaded pedaling (change in maximum oxygen uptake (delta VO2max) and in anaerobic threshold (delta AT). On average, obese children's responses were in the normal range: delta VO2max, 104 +/- 41% (+/- SD) predicted (by age); delta AT, 85 +/- 51%; ratio of change in VE to change in VCO2, 111 +/- 21% and ratio of change in VO2 to change in work rate, 100 +/- 24%, but six of the obese children had values of delta VO2max or delta AT that were more than 2 SD below normal. In addition, obese children did not have increased delta VO2max or delta AT with age as observed in nonobese children. Although the response time of VO2 was normal (99 +/- 32% of predicted), those for both VCO2 and VE were prolonged. We conclude that the finding of obesity in a child is not a reliable indicator of poor fitness but that testing cardiorespiratory responses to exercise can be used to identify subjects with serious impairment and to individualize therapy. PMID- 2105387 TI - Taurine depletion in very low birth weight infants receiving prolonged total parenteral nutrition: role of renal immaturity. AB - In a prospective, controlled study, plasma and urinary taurine concentrations were determined weekly, between postnatal weeks 3 and 18, in (1) seven sick infants (gestational age less than 28 weeks, birth weight less than or equal to 1000 gm) who received a taurine-free total parenteral nutrition solution for 32 to 49 days (group P) and who subsequently were formula fed and (2) eight sick infants matched by gestational age and birth weight, who received formula or human milk from day 3 to 4 of life (group E). Ten healthy full-term infants ranging in age from 1 to 18 weeks and fed with formula provided normal values (group C). Significantly lower mean plasma taurine values (range 1.59 to 3.43 mumol/dl) were found between postnatal weeks 3 and 7 in group P compared with group E (range 5.54 to 6.97 mumol/dl) and with group C (5.6 +/- 0.34 mumol/dl). After initiation of feeding, plasma taurine concentrations in group P increased to normal. Markedly elevated values of mean fractional excretion of taurine, 38% to 56%, were found between weeks 3 and 5 in group P and E compared with group C (15.5 +/- 3.2%). In contrast, during the same period, low urinary taurine values (4.9% to 6.7%) were found in two larger, older infants receiving total parenteral nutrition whose plasma taurine values were in the normal range. After week 5, urinary taurine values were in the control range in all groups. We conclude that the absence of taurine in total parenteral nutrition solutions administered to very low birth weight infants and the limited ability of the immature kidney to adapt to low taurine intake by "up-regulation" of tubular taurine reabsorption may result in depleted taurine body pools during the first weeks of life. This inability to conserve taurine by the immature nephron could potentially have a deleterious effect on the developing brain and retina in these infants, and indicates a possible need for taurine supplementation. PMID- 2105388 TI - Solubility of calcium and phosphorus in parenteral nutrition solutions. PMID- 2105389 TI - Pathology of experimental Sarcocystis falcatula infections of canaries (Serinus canarius) and pigeons (Columba livia). AB - Sarcocystis falcatula is an apicomplexan parasite with a broad range of avian intermediate hosts. The pathology and pathogenesis of infection with this parasite has been studied experimentally in the budgerigar (Melopsittacus undulatus). The present study quantitatively examines the pathology of this parasite in canaries (Serinus canarius) and pigeons (Columba livia) and compares it with that found in budgerigars. The general progression of merogony and cyst formation is similar qualitatively to that seen in budgerigars, but it differs quantitatively. The principal site of precystic merogony is in pulmonary endothelial cells. The magnitude of pulmonary meront burdens (at similar inoculated dosages) varies in different intermediate host species. Merogony is less persistent than in budgerigars. Among the various species of birds, the magnitude of precystic merogony correlates differently with the magnitude of skeletal muscle cyst burdens. The distribution of cyst burdens among various muscles also differs. The composition of inflammatory cells differs among various avian species' response to S. falcatula. Pathologic changes quantitatively parallel tissue meront burdens (except possibly in the liver of canaries), resulting in an interstitial pneumonitis, hepatitis, and mild inflammatory lesions of other organs. PMID- 2105390 TI - The effects of enteral stimulation on gallbladder bile during total parenteral nutrition in the neonatal piglet. AB - The neonatal piglet is a satisfactory model for the human neonate requiring total parenteral nutrition (TPN). Bile status and subsequent liver and gallbladder dysfunction have long been documented as serious complications of long-term TPN. The purpose of this study was to determine whether small amounts of enteral formula during TPN will maintain normal bile appearance and composition. Thirty one Hanford miniswine, 3 to 6 days old underwent surgery for the placement of central venous catheters. Two days postoperatively, the animals were separated into three groups, according to dietary regimens. Group 1 (n = 10), the control group, received pig formula (SPF-lac) orally (200 cal/kg/d); group 2 (n = 11), was maintained on TPN (180 cal/kg/d) with an enteral supplement of SPF-lac (20 cal/kg/d); group 3 (n = 10), was maintained on TPN only (200 cal/kg/d). The TPN formula consisted of 35 g/kg/d of glucose, 10 g/kg/d of protein, and 3 g/kg/d of lipid. The animals were maintained on these diets for 6 weeks. At necropsy, gallbladder with bile was weighed and bile volume and appearance was recorded. Chemical analyses was performed on 26 bile samples. Gallbladder weight was significantly decreased in groups 2 and 3 compared with group 1 (P less than .0003, P less than .033, respectively, using Students t test with Bonferoni adjustment). Volume was significantly decreased only in group 2 (P less than .003). Group differentiation in relation to bile appearance was determined by the presence or absence of either bile sludge or crystals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105391 TI - Modification of cardiopulmonary hemodynamics and vasoactive mediators by extracorporeal membrane oxygenation in newborn lambs. AB - We asked if prolonged venoarterial extracorporeal membrane oxygenation (ECMO) causes alterations in cardiopulmonary hemodynamics that might be reflected in arbiters of vascular tone: thromboxane, prostacylin, norepinephrine, and epinephrine. Newborn lambs undergoing ECMO demonstrated significant augmentation of systemic and pulmonary arterial blood pressure that was temporally related to rises in all vasoactive mediators measured. Although the prostanoids returned to baseline within 30 minutes, the catecholamines remained elevated significantly throughout bypass. Long-term bypass, however, was not associated with sustained systemic hypertension. Pulmonary hypertension was achieved only after 6 hours of bypass. These acute and chronic changes may exacerbate a pathological state for which ECMO is indicated. PMID- 2105392 TI - Study of tachyphylaxis to the vasoconstrictor effect of arachidonic acid in the isolated perfused kidney of the rat. AB - The isolated perfused kidney of the rat was used to address the development of tachyphylaxis to the vasoconstrictor effects of arachidonic acid. Repeated administration of arachidonic acid (3 micrograms at 10-min intervals) to the isolated kidney of the rat, perfused in situ with Krebs-Henseleit solution, led to the development of tachyphylaxis to the renal vasoconstrictor effects of arachidonic acid, using perfusion pressure changes as an index. Vasoconstrictor responses to either angiotensin or the endoperoxide analog, U46619, were unaffected by repeated administration of arachidonic acid. Associated with progressively reduced renal vasoconstrictor responses to arachidonic acid were parallel decrements in the renal venous release of prostanoids, measured by radioimmunoassay. In contrast, the release of prostanoids from the kidney stimulated by angiotensin II was increased after repeated administrations of arachidonic acid. These data suggest that the sequential reduction in renal vasoconstrictor responses to arachidonic acid is due to diminished conversion to prostaglandins, possibly due to inactivation of cyclooxygenase, decreased entry of arachidonic acid into the cell or its increased esterification into phospholipids. PMID- 2105393 TI - Mechanism of vascular actions of prostacyclin in the rat isolated perfused mesenteric arteries. AB - Prostacyclin (PGI2) did not alter the basal perfusion pressure in the isolated rat mesenteric arteries perfused with Krebs' solution, but produced a biphasic effect in arteries preconstricted with norepinephrine or arginine vasopressin: constriction, then prolonged dilation. Both these components of PGI2 effect were diminished in arteries denuded of their endothelia by a 10 min perfusion with distilled water or p-bromophenacyl bromide (10 microM). The present study elucidates the mechanism of these PGI2 actions. Indomethacin (0.28 microM) SQ 29548 (1 microM, thromboxane A2 receptor antagonist), saralasin (1 microM, angiotensin II receptor antagonist) or the free radical scavengers, superoxide dismutase (60 U/ml) and catalase (40 U/ml) did not inhibit the initial vasoconstriction, suggesting it was not mediated through endothelially generated thromboxane A2, angiotensin II or oxygen-derived free radicals. However, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (50 microM; Ca++ chelating agent), 8-(diethyl-amino)octyl 3,4,5-trimethoxy benzoate (10 microM; intracellular Ca++ antagonist), or neomycin (5 mM; phospholipase-C inhibitor) abolished the vasoconstriction. Ouabain (0.5 mM) did not affect the vasodilation, but perfusion with excess (50 mM) or 0 K+ Krebs' solution abolished it, suggesting this PGI2 action involves changes in membrane K+ conductance via a mechanism independent of Na+/K+ adenosine triphosphatase. Vasodilation evoked by BRL 34915 (K+ channel activator) was similarly attenuated under these conditions, but not by ouabain. Furthermore, procaine (1 mM; nonspecific K+ channel inhibitor), but not apamin (0.5 microM) or tetraethylammonium (10 mM) blocked PGI2- and BRL 34915-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105394 TI - Effects of indomethacin on neural and myogenic components in equine airway smooth muscle. AB - Equine airway smooth muscle is innervated by vagal efferents and, in addition, displays spontaneous mechanical activity. The preparation thus appears to contain at least two discrete excitable components, the cholinergic neural elements and the smooth muscle membrane. Indomethacin (INDO), a cyclooxygenase (CO) inhibitor, exerts a considerable potentiation of function in this preparation. The latter may be effected indirectly, through loss of the inhibitory effect of endogenous prostaglandin E2 (PGE2) on neural acetylcholine release and through direct effects on smooth muscle of the generally antagonistic CO and lipoxygenase (LO) metabolites. The present studies were designed to assess the relative contributions of altered arachidonic acid metabolism on those respective elements. The utility of the model, in terms of distinguishing neural and myogenic components, was assessed by examining the effects of the muscarinic antagonist atropine (ATR) and the neurotoxin tetrodotoxin (TTX) on the stimulus response (SR) relationship. The observations that TTX and ATR produced similar rightward (but not downward) shifts of the SR curve and that D-600 inhibited the TTX-insensitive responses are consistent with a selective activation of the muscle by the nerves at lower voltages and a direct stimulation of the muscle at higher voltages. INDO potentiated both the neural and myogenic components of the SR curve, effects which were sensitive to ATR and 5,8,11,14-eicosatetraynoic acid, an inhibitor of LO, and reversed by PGE2. The finding that PGE2 at low doses (10(-8) M) inhibited responses at lower voltages and that at higher concentration (10(-7) M) it shifted the SR curve right and downward suggested that neurotransmitter release is more sensitive to PGE2 inhibition than is muscle response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105395 TI - Hemolytic disease of the newborn as an unusual consequence of drug abuse. A case report. AB - Severe Rhesus isoimmunization occurred in a primigravida following self-injection of her partner's blood as a consequence of drug abuse. This case demonstrated the value of the true sinusoidal fetal heart rate pattern as an indicator of severe fetal compromise. PMID- 2105396 TI - New inhibitors of renin that contain novel phosphostatine Leu-Val replacements. AB - A novel series of renin inhibitors based on the Phe8-His9-Leu10-Val11 substructure of renin's natural substrate, angiotensinogen, is reported. These inhibitors retain the Phe8-His9 portion of the native substructure and employ novel phosphostatine Leu10-Val11 replacements (LVRs). The phosphostatine LVRs were prepared by condensing a dialkyl phosphonate ester stabilized anion with either N-t-Boc-amino aldehydes or N-tritylamino aldehydes (derived from the corresponding amino acid). Structure-activity relationships at the Leu10 side chain revealed that the LVR derived from L-cyclohexylalanine provided a 130-fold boost in potency over the LVR derived from L-leucine. The dialkyl ester moiety was varied and a loss in potency was incurred when the alkyl ester was chain extended or alpha-branched; dimethyl esters provided optimum potency. The phosphonate moiety was replaced by a half-acid half-ester phosphonate and dimethylphosphinate; both replacements lead to a loss in potency. The more potent inhibitors (IC50 = 20-50 nM) were found to be selective inhibitors for renin over porcine pepsin and bovine cathepsin D (little or no inhibition was observed at 10(-5) M). PMID- 2105397 TI - Probing DNA structure and function with a multi-wavelength fluorescence confocal laser microscope. AB - Three levels of organization in DNA structure in the interphase cell nucleus are assessed by confocal laser scanning microscopy: (i) the conformational state of the double helix; (ii) the distribution of eu- and heterochromatin; and (iii) the localization of replication complexes throughout S phase. Multi-parameter measurements were carried out in each optical section using two laser sources and combined stereoscopic reconstructions were used to assess the co-localization of nuclear components. DNA is highly polymorphic and can adopt a variety of different helical conformations as well as unusual structures (curved, cruciform, multi-stranded). We have assessed by laser scanning microscopy the presence of left-handed Z-DNA in polytene chromosomes of Diptera as well as the spatio temporal distribution of Z-DNA binding proteins in whole-mount Drosophila embryos and ovaries. We have determined the 3-D distribution of replication sites relative to heterochromatin regions, nucleoli and nuclear membrane by using short pulses of BrdU incorporation in synchronized mouse and human fibroblasts. Replication sites were visualized with a monoclonal anti-BrdU antibody combined with DNA fluorescent staining and antibody labelling of nuclear lamin. The implications of dynamic DNA movement and structural rearrangement to the organization of the nucleus in domains are discussed. PMID- 2105398 TI - Zn2+ regulation of ornithine transcarbamoylase. I. Mechanism of action. AB - Ornithine transcarbamoylase catalyzes the formation of L-citrulline from carbamoyl phosphate and L-ornithine. The anabolic enzyme from Escherichia coli is composed of three identical subunits and resembles, in both primary and quaternary structures, the catalytic unit of aspartate transcarbamoylase. However, ornithine transcarbamoylase has no regulatory subunits. Although this enzyme does not bind its substrates co-operatively, fluorescence spectroscopic experiments show that zinc adds allosterically to the free enzyme. The metal binding process is dictated by deprotonation of an enzymic group with a pKa less than 7. The saturation binding curve of the metal ion is sigmoidal and yields a Hill coefficient of 1.6 at pH 8.5 and 25 degrees C. In the absence of substrates, zinc further promotes a slow enzyme isomerization, which occurs with a first order rate constant of 7 min-1; thus, the metal is a slow, tight-binding inhibitor. The isomerized enzyme is inactive and contains three zinc ions. When the enzyme is first bound with carbamoyl phosphate, steady-state kinetic assays reveal that zinc again binds co-operatively to the binary enzyme complex, with a Hill coefficient of 1.5, but the metal ion now behaves simply as a classical, reversible inhibitor; it is competitive against L-ornithine, non-competitive against carbamoyl phosphate, and induces no enzyme isomerization. However, as a result of the competition between zinc and L-ornithine for the same site on the enzyme, the L-ornithine saturation curve becomes sigmoidal. Displacement of the allosteric zinc from the enzyme by L-ornithine is the cause of co-operative addition of this substrate. The combined results suggest that zinc regulates ornithine transcarbamoylase via two routes: (1) as an allosteric cofactor of the substrate-bound enzyme in mediating site-site interactions; and (2) as a slow, tight-binding inhibitor of the free enzyme in inducing inactivation. The concentration of zinc that is effective for action is in the micromolar range. The finding that E. coli ornithine transcarbamoylase can be induced to express co operativity in binding its substrates has recently been confirmed by site directed mutagenesis experiments. When the active site residue Arg106 is altered to a glycine, the resultant mutant enzyme exhibits both homotropic and heterotropic interactions towards its substrates. In view of the quaternary structure of holoenzyme aspartate transcarbamoylase, the "silent" co-operativity of ornithine transcarbamoylase is of particular interest in the study of evolution of complex, regulatory proteins. PMID- 2105399 TI - Spontaneous rupture of a bladder diverticulum. AB - A case of spontaneous rupture of an acquired bladder diverticulum is presented. Diagnosis was made preoperatively and full recovery followed surgical treatment. A review of the literature revealed 9 other cases of spontaneous rupture. Bladder outlet obstruction and urinary tract infection were present in the majority of cases. In the past misdiagnosis and delayed treatment led to significant mortality. However, the prognosis currently is better due to the use of broad spectrum antibiotics, better radiological imaging studies, and earlier diagnosis and treatment. PMID- 2105400 TI - Differential effects of a gram-negative and a gram-positive infection on autogenous and prosthetic grafts. AB - A canine model was developed to study the differential response of a gram negative and a gram-positive bacterial infection on autogenous and prosthetic grafts. After replacing segments of the femoral arteries of 15 dogs with autogenous vein in one groin and polytetrafluoroethylene in the contralateral groin, 10(8) colony-forming units of nonmucin-producing Staphylococcus epidermidis (five dogs), Pseudomonas aeruginosa (five dogs), or sterile saline solution (five dogs) were directly inoculated onto the grafts. The grafts were examined 7 to 10 days after implantation. None of the control dogs exhibited inflammatory signs, and no grafts or anastomoses disrupted. S. epidermidis was unrecoverable from either graft material in any of the animals, although histologic evaluation confirmed neutrophils and bacteria in four of five animals in the vein and polytetrafluoroethylene groups. No dog inoculated with S. epidermidis had graft or anastomotic disruption. By contrast, P. aeruginosa was recovered from both types of grafts in all inoculated animals. Neutrophils, bacteria, and microabscesses were observed in all of these animals. In addition, three of five polytetrafluoroethylene grafts and all five vein grafts disrupted either at the anastomoses or in the body of the vein graft. Therefore S. epidermidis is a less virulent organism that may persist in graft walls despite negative cultures, whereas P. aeruginosa is a highly virulent organism that can disrupt native artery, vein grafts, and anastomoses. The graft material appears to be less important than the bacteria in determining the outcome of infection. PMID- 2105401 TI - Inadequacy of diagnosis related group (DRG) reimbursements for limb salvage lower extremity arterial reconstructions. Ad hoc committee of the Joint Council of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery. AB - Prospective cost and reimbursement data were collected from 10 centers in various parts of the United States on 566 patients undergoing lower extremity arterial reconstructions for limb salvage and nonlimb salvage indications. Information for each patient was available on indication and type of procedure, length of stay, the type of hospital insurance, and hospital costs/charges. Diagnosis related group payments from each center were used to determine net gain or loss for each patient. Patients were classified as having claudication or critical ischemia (limb salvage). Reimbursements matched costs/charges for the claudication group; overall mean loss in this group was only $915 per patient. However, all centers had important losses in the limb salvage group. Reimbursements averaged 60% of costs/charges, with a mean loss of $8158 per patient and an overall loss for all 10 centers of $3,653,918. An effort to remedy this inequity is progressing via a dialogue between representatives of the Society for Vascular Surgery, the North American Chapter of the International Society for Cardiovascular Surgery, and the federal government. PMID- 2105402 TI - Enhancing the carotenoid content of atherosclerotic plaque: implications for laser therapy. PMID- 2105403 TI - From the Centers for Disease Control. Aspergillus endophthalmitis in intravenous drug users--Kentucky. PMID- 2105404 TI - Development of clinical and economic prognoses from Medicare claims data. AB - Using a 5% nationally random sample of Medicare beneficiaries, we calculated the probability of dying, the probability of being readmitted, and the mean level of inpatient hospital expenditures within various time periods following discharge for those beneficiaries who were discharged alive from an acute-care hospital during 1983. We then examined the 674 most common principal discharge diagnoses and found significant variations by diagnosis code for all three outcomes. We believe that analyses of claims data by diagnosis code can provide useful information to clinicians and their patients regarding the clinical and economic prognosis of specific diseases, help managed-care programs identify patients likely to incur substantial costs over a several-year period, and inform insurers regarding the expected level of resources that will be used following discharge for patients with specific diseases. PMID- 2105405 TI - [An advanced gastric carcinoma which responded to combined administration of mitomycin C, FT-207, and lentinan immunochemotherapy]. AB - A 59-year-old man with a gastric cancer underwent a laparotomy and was found to have an unresectable tumor that formed a large mass with metastatic lymph nodes around the aorta. He therefore was treated by a combined administration of Mitomycin C, FT-207, and Lentinan for 3 months. Remarkable tumor reduction was observed endoscopically, and a subtotal gastrectomy was performed. The immunochemotherapy then was resumed, and the patient has survived for 16 months despite the remnant lymph node metastases. A histological examination of the resected stomach revealed a marked degeneration of the tumor. PMID- 2105406 TI - Effects of dietary fish oil on renal growth and function in uninephrectomized rats. AB - The basic mechanisms of renal growth remain poorly understood. The work hypertrophy theory holds that after an acute reduction in renal mass, the growth of the kidney occurs as a consequence of increased renal function. Pharmacological inhibition of renal prostaglandin synthesis impairs the acute adaptive increases in both renal function and mass following partial nephrectomy. The present study examines the effects of four weeks of dietary fish oil on renal growth, function and arachidonic acid metabolites in intact and uninephrectomized male Sprague-Dawley rats. Dietary fish oil interferes with dienoic prostaglandin and thromboxane production in favor of synthesis of trienoic analogues. Control animals were pair-fed an identical diet with the exception that the fat was replaced by beef tallow. Renal cortical concentrations of arachidonic acid metabolites were reduced in animals fed fish oil, and urinary excretion of prostaglandin E2 was impaired. Fish oil feeding resulted in increased kidney weight without concomitant increases in renal function in intact animals. Glomerular filtration rate and renal plasma flow were greater in uninephrectomized rats fed fish oil compared to uninephrectomized controls pair fed beef tallow. Augmentation of the compensatory increases in renal function observed with fish oil feeding was not associated with any additional renal hypertrophy. These data indicate that dietary fish oil has a profound impact on renal growth and function, which may be the consequence of altered renal and/or extrarenal arachidonic acid metabolism. Furthermore, the direction of the alterations in renal mass oppose that of renal function, providing clear and unique evidence against the work hypertrophy theory of renal growth. PMID- 2105407 TI - Cytochrome P450-dependent arachidonic acid metabolism in human kidney. AB - Cytochrome P450-dependent arachidonic acid metabolism in human kidney cortex from several postmortem subjects has been characterized. Using HPLC and GC/MS, four cytochrome P450-arachidonic acid metabolites were tentatively but not unequivocally identified as epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acid (DHT) and 19- and 20-hydroxyeicosatetraenoic acids, suggesting the involvement of two major cytochrome P450 enzymes, epoxygenase and omega/omega-1 hydroxylases. This pattern of metabolism was similar to that found in rabbit and rat kidneys. The formation of these metabolites was dependent on the presence of NADPH and inhibited by IgG of NADPH-cytochrome P450 (c) reductase. Immunologic studies of renal cytochrome P450 epoxygenase demonstrated that antibodies prepared against human-purified hepatic cytochrome P450 epoxygenase recognized renal enzyme protein and inhibited the enzyme activity by 92%. In contrast, control immunoglobulin did not inhibit renal cytochrome P450 epoxygenase. Antibody inhibition of renal cytochrome P450 epoxygenase demonstrated a degree of conservation of both enzyme proteins between liver and kidney. Antibodies against lauric acid omega/omega-1 hydroxylases (P450 omega) inhibited the formation of omega/omega-1 hydroxylase products, 19- and 20-HETEs. Identical qualitative patterns of arachidonic acid metabolites were observed in all cortical microsomes studied. Interindividual variations were observed in the cytochrome P450-dependent arachidonic acid metabolism, and the activities ranged from 0.031 to 5.027 nmol arachidonic acid converted/mg protein/30 min. which is about a 150-fold difference. However, when the specific activities for total cytochrome P450-dependent arachidonic acid metabolism were calculated, two separate groups could be distinguished, high and low metabolizers of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105409 TI - Pulmonary function and bronchial reactivity in asthmatics during low-level formaldehyde exposure. AB - This study evaluated whether formaldehyde, at concentrations similar to those found in the indoor environment, could produce adverse effects on the lower airway of 15 asthmatic persons with documented bronchial hyperresponsiveness who were exposed for 90 min in a climate chamber to clean air containing formaldehyde vapor at levels of 0.85 mg/m3, 0.12 mg/m3, and 0.008 mg/m3. No significant changes in forced expiratory volume in 1 sec (FEV1), airway resistance (Raw), specific airway resistance (SRaw), and flow-volume curves could be detected during formaldehyde exposure. Furthermore, histamine challenge tests performed immediately after formaldehyde exposure showed no evidence of changes in bronchial reactivity. No late reactions were registered during the first 14-16 hr after exposure. The results suggest that residential levels of formaldehyde are of minor importance in the emergence of pulmonary symptoms. Discrepancies between the present study and previous data may be due to differences in environmental conditions. PMID- 2105408 TI - Effect of uremia and its treatment on pulmonary function. AB - Alterations in respiratory drive, mechanics, muscle function, and gas exchange are frequent if not invariable consequences of uremia. Pulmonary dysfunction may be the direct result of circulating uremic toxins or may result indirectly from volume overload, anemia, immune suppression, extraosseous calcification, malnutrition, electrolyte disorders, and/or acidbase imbalances. The pulmonary system is unique because it is affected by the disease and its treatment. Acetate hemodialysis reduces alveolar ventilation and PaO2 due to extrapulmonic CO2 unloading. Peritoneal dialysis increases alveolar ventilation and intraperitoneal pressure. The latter leads to an elevated and lengthened diaphragm, a reduced functional residual capacity, basilar atelectasis, possible hypoxemia, and altered respiratory muscle function. In patients on chronic peritoneal dialysis, adaptations may occur that limit the reductions in lung volumes, PaO2, and respiratory muscle strength that are often observed during acute peritoneal dialysis. This review details how uremia and dialysis interact to alter pulmonary function. PMID- 2105410 TI - Breathing pattern affects respiratory heat loss but not bronchoconstrictor response in asthma. AB - To determine whether changes in breathing pattern alone affect respiratory heat loss (RHL) and the constrictor response to cold dry gas hyperpnea in asthmatic subjects, we performed the following 2 part study: first we measured RHL in 8 asthmatic and 8 normal subjects during controlled eucapnic hyperpnea while they breathed at inspiratory to expiratory ratios (I/E) of 1:3, 3:1, and 2:2, and we recorded postchallenge forced expiratory volume in 1 sec (FEV1) in the asthmatic group; we then performed the same measurements in 8 asthmatic and 8 normal subjects at fixed target minute ventilation (VE) for tidal volumes of 0.2 X Forced vital capacity (FVC), 0.4 X FVC, and 0.6 X FVC by varying the target respiratory rate appropriately. Our results show that (1) increasing I/E ratio or tidal volume-frequency ratio (VT/f) at fixed VE produced small but statistically significant increases (p less than 0.05) in overall heat loss per unit volume of respired gas (RHL/VE) in both asthmatic and nonasthmatic subjects of 1-4 cal/L; (2) changes in breathing pattern alone did not affect bronchoconstrictor response as assessed by lack of change in slopes and intercepts of % delta FEV1 vs. RHL dose-response curves; and (3) the increase in RHL per unit volume of respired gas resulting from increasing VT/f ratios during cold gas hyperpnea was significantly greater in asthmatic than in nonasthmatic subjects. We conclude that changes in breathing pattern may affect overall RHL measured at the mouth, although the maximum effect of such changes in both asthmatic and nonasthmatic subjects is small (10-15%); that such changes do not significantly alter airway constrictor response in asthmatic persons; and (3) that the effects of changing breathing pattern on RHL may be more pronounced in asthmatic than nonasthmatic subjects, which suggests that the asthmatic group may be less able to adapt to factors that alter the magnitude and site of RHL. PMID- 2105411 TI - Lipid peroxidation and lung ultrastructural changes in an experimental model of leukocyte-mediated pulmonary injury. AB - The aim of this study was to study ultrastructural changes and lipid peroxidation in rabbits lung after massive complement activation and leukocyte aggregation. A prolonged and massive leukocyte activation was induced by intraperitoneal inoculation of zymosan suspected in paraffin. Fifteen animals (group 3) were given 0.6 g/kg of zymosan, 22 animals (group 2) received 1 g/kg, and 11 rabbits (group 1) were treated with paraffin alone and served as controls. An acute mortality rate of 40% was observed in group 3 and of 68% in group 2. Surviving animals were studied for 10 days. In these animals a marked decrease in circulating granulocytes and a progressive decline in arterial PO2 were recorded (PO2 on day 10 in group 2 animals was 51.94 +/- 4.26, p less than 0.01). Microscopic and ultrastructural evaluation revealed sequestration of granulocytes in the pulmonary microvasculature. Studies of lung homogenates demonstrated increased levels of lipid peroxide derivative malondialdehyde (group 2 rabbits, 1624 +/- 638; group 1, 795 +/- 57 pm/mg pt, p less than .001) and decreased levels of the tissue antioxidant alpha-tocopherol. The results of this study are compatible with the hypothesis of leukocyte-mediated injury through production of oxygen radicals. PMID- 2105412 TI - Positive influence of nifedipine on early-stage minipig shock lung. AB - Mechanical and biochemical lesions can be observed in shock lung. To investigate the influence of the calcium antagonist nifedipine on these lesions, we produced shock lung in male minipigs. Three groups (control, thrombin, and thrombin + nifedipine; n = 5) were formed. In the second and third group thrombin was administered intravenously (400 IU/kg body weight) over a period of 2 h. After that the animals received aminocaproic acid (100 mg/kg body weight/h) throughout the rest of the study. Nifedipine was administered in the third group at a dosage of 46 micrograms/kg body weight/h. During the investigation period coagulation and hemodynamic status were examined as well as blood gas levels. Then the isolated lungs were examined. Without nifedipine there was a significant decrease in arterial PO2, an increase in airway opening pressure (Pi), and a decrease in weight-specific end-inspiratory lung compliance (Ci). These changes were not observed under the influence of nifedipine, after which the results were similar to the control group. This demonstrates a positive influence of nifedipine on the acid-base status and the investigated lung mechanical parameters. PMID- 2105413 TI - High-cost patients in a fee-for-service medical plan. The case for earlier intervention. AB - This article describes the high-cost and very high-cost patients in the fee-for service medical plan of one of the nation's largest banks in terms of their demographics and medical plan expenses and utilization, within a single year and during a period of 4 consecutive years. High-cost patients ($5,000-25,000 annually) were dominated by older persons and women 20 to 39 years, while the very high-cost patients (at least $25,000) tended to be older men and infants of both genders. Very high-cost patients used 5 to 7 times more hospital patient days and visited with a physician on an outpatient basis twice as often as high cost patients. In turn, the high-cost patients experienced 37 to 50 times as many patient days and twice as many outpatient visits as patients whose annual expenses were below $5,000. Longitudinal analyses suggested that while most of the high-cost patients are typically low-cost patients or nonusers of services who experience high-cost time spans, some of them suffer from more serious chronic health problems and are apt to become very high-cost patients. Focusing case-management interventions on this small subgroup of high-cost patients may prevent some very high-cost cases in the future. PMID- 2105414 TI - The impact of DRG-based budgeting on inpatient psychiatric care in Veterans Administration medical centers. AB - In 1985 the Veterans Administration (VA) implemented a prospective budgeting system for acute inpatient care based on diagnosis-related groups (DRGs). To assess the impact of this system on psychiatric care, this study reviewed data on all VA discharges for psychiatric or substance abuse disorders that occurred during the four years before and the four years after this system was implemented. During the four years following the implementation of DRG-based budgeting the number of annual discharges increased by 28.7% and the number of unique patients discharged increased by 15.5%. Average lengths of stay declined by 36.9% and total annual bed days of care per unique patient declined by 29.7%. These changes occurred in association with an 11.5% reduction in the total number of beds occupied by psychiatric patients, an 8.9% reduction in direct per diem expenditures for psychiatric care nationally, and a 32.7% decline in direct expenditures per episode, after adjustment is made for inflation. In spite of a continuing decline in the value of the available resources, largely due to the effect of inflation, prospective budgeting appears to have had a major impact on the pattern of inpatient psychiatric care in this large health care system. PMID- 2105415 TI - Case-mix classification for emergency departments. AB - This study developed a patient classification system for hospital emergency departments. Conducted at three Los Angeles area community hospitals, data collection included coding and abstracting medical records information, patient billing information detailing each patient's utilization of hospital services, and patient-specific provider time measuring each provider's time spent in direct patient care activities. A 20,000 patient sample was derived containing clinical and resource use variables, including physician, emergency department, and ancillary service direct costs. Patient visits were classified into 216 homogeneous groups, or patient clusters, using four types of variables: diagnoses, disposition, age, and physician procedures. The Emergency Department Groups (EDGs) appear to represent a clinically coherent system for classifying emergency department visits; moreover, the groups were found to explain 63% of the overall variance in resource use (total direct cost) suggesting that the EDGs may offer a useful tool for hospital cost control and reimbursement reform. PMID- 2105416 TI - [The pattern of non-A, non-B hepatitis is more and more evident. A new test for diagnosis of hepatitis C makes it possible to mass screen blood donors]. PMID- 2105417 TI - [A new serologic test makes it possible to diagnose hepatitis C]. PMID- 2105418 TI - [Suscard nitroglycerin and caries]. PMID- 2105419 TI - [Large-scale economic benefits of behavioral therapy of persons needing assistance in travelling because of phobia]. PMID- 2105420 TI - Inhibition of adenylate cyclase activity by polyamines in human erythrocyte plasma membranes. AB - Polyamines (spermidine, spermine and putrescine) inhibited the adenylate cyclase activity in a concentration dependent manner in human erythrocyte plasma membranes. Spermidine (Spd) exhibited more inhibitory effect than spermine (Spm) and putrescine (Put). On the contrary, the addition of amino acids (arginine, glutamine and lysine) did not influence the basal enzyme activity. Other cations (polylysine, polyarginine and polyglutamine) also did not affect the enzyme activity. Addition of all the three polyamines (Spd, Spm and Put) in the reaction mixture exhibited moderate inhibitory effect on the adenylate cyclase activity whether it was basal or activated with sodium fluoride or with forskolin. Since the three polyamines exhibited maximum inhibitory effect at 10 microM concentration which is within physiological limit for mammalian tissues, we suggest that there may be a regulatory function of these molecules on adenylate cyclase activity in human erythrocytes. PMID- 2105421 TI - Education to prevent preterm labor. PMID- 2105422 TI - Networking about infants at high risk. PMID- 2105423 TI - Privileged communication--talking with a dying adolescent. AB - For an adolescent who is dying, the opportunity to experience control, autonomy, and a feeling of belonging eases uncertainty and turmoil. PMID- 2105424 TI - Grief of an adolescent when a sibling dies. AB - Grieving for losses that normally occur during adolescent development, and at the same time grieving the loss of a sibling cannot be clinically separated. PMID- 2105425 TI - Assessing and managing agitation in a critically ill infant. AB - Agitation may be caused by respiratory insufficiency, pain, or environmental factors. Among its treatments are mechanical ventilation, comfort measures, and a variety of medications. Skillful intervention is essential to combine and monitor therapies and to wean infants from some medications. PMID- 2105426 TI - A device for supplementing breast-feeding. AB - A device for providing additional nourishment to a breast-fed infant may be constructed to address two key problems of supplemental feeding. PMID- 2105427 TI - Update on cancer risk and oral contraceptives. PMID- 2105428 TI - Maternal liability for fetal injury? PMID- 2105429 TI - Infant kidnapping: it can happen in any hospital. PMID- 2105430 TI - Measuring nursing concepts. PMID- 2105431 TI - Practicing nurses: credible leaders in designing and giving care. PMID- 2105432 TI - Advanced practice nursing: a model of collaborative care. PMID- 2105433 TI - Molecular analysis of duplicated esterase genes in Drosophila melanogaster. AB - Genomic clones containing sequences homologous to an esterase 6 (Est-6) cDNA clone were isolated from a library of Drosophila melanogaster DNA. Comparison of the genomic and cDNA sequences revealed that the Est-6 gene comprises two exons, one of 1,387 bp and one of 248 bp, separated by a short intron of 51 bp. Further sequencing revealed the presence of a tandem duplication of the Est-6 gene (denoted Est-P) which also has an exon of 1,387 bp and an exon of 248 bp, separated by a short intron of 56 bp. The two genes show similarities of 64% and 60% at the DNA and protein levels, respectively. The coding regions of the genes are 197 bases apart, and presumptive 5' regulatory sequences of Est-P overlap at least the 3' noncoding region of Est-6. Transcripts homologous to Est-P were detected in late larvae and adults of each sex, whereas Est-6 transcripts are present in all life stages but are predominant in adult males. This suggests different physiological functions for the products of the two genes. Southern and Northern blot hybridization analyses of the 20-kb region surrounding the Est 6/Est-P duplication failed to detect any other duplicated esterase genes, although this region is actively transcribed. PMID- 2105434 TI - Studies of antiproteolytic effects of glyburide on rat L6 myoblasts: comparisons with insulin. AB - Cultured L6 myoblasts afford considerable advantages for identifying and studying the insulin-like actions of test substances in a muscle-derived line. We have used this system to examine the interaction of the oral hypoglycemic sulfonylurea glyburide with bovine insulin on protein degradation and synthesis as well as on thymidine incorporation (as a measure of DNA synthesis) in these cells. Bovine insulin, at doses of 0.1 microgram/mL to 10 micrograms/mL, produced a dose dependent inhibition of protein degradation (measured by release of trichloracetic acid (TCA)-soluble 14C-tyrosine from myoblasts into the culture medium) and increase in total protein content in the cultured myoblasts. At concentrations of 10 micrograms/mL, insulin achieved its maximal suppression of protein degradation (by nearly 50%) and increased cellular protein content (by 15%) over levels observed in the absence of added insulin. Glyburide, at concentrations at or above 1 microgram/mL, significantly suppressed protein degradation (up to 14%) and slightly augmented protein content of the cells. The effects of glyburide on protein degradation were additive with those of submaximally but not maximally effective concentrations of insulin, suggesting a common mechanism of action of the compounds. Both insulin and glyburide, at maximally effective doses, significantly depressed protein degradation as early as 2 to 6 hours after exposure. In addition, in a 24-hour labeling experiment, insulin stimulated tyrosine incorporation into TCA-insoluble protein and thymidine incorporation into DNA in the cells, whereas glyburide did not enhance these processes and, under certain conditions, inhibited them. These results demonstrate that glyburide, either alone or in concert with insulin, is capable of significantly inhibiting protein turnover in skeletal muscle-derived cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105435 TI - A method for the massive separation of highly purified, adult porcine islets of Langerhans. AB - A method for the massive and reproducible isolation of highly purified, adult porcine islets of Langerhans is described. The successful combination of donor animal-strain selection with original procedures for pancreas retrieval and enzymatic digestion permitted us to separate uniquely massive concentrations of pure porcine islets with no need for mechanical disruption of the pancreatic tissue. Following our procedure, porcine islets, which fully retain viability and function, can be harvested easily and rapidly. Xenotransplantation of such islets, immunoprotected within algin/polyaminoacidic microcapsules, was associated with complete reversal of hyperglycemia in rodents with either spontaneous or streptozotocin-induced diabetes mellitus. PMID- 2105436 TI - Lipid and apoprotein modifications in body builders during and after self administration of anabolic steroids. AB - To determine the effects of anabolic steroids on serum lipid and apoprotein levels, 14 white male body builders who self-administered steroids for 2 to 3 months (steroid users) were studied; 10 agreed to screening while they were taking the drugs (ON treatment) and also at about 3 months following their suspension (OFF treatment). Controls consisted of 17 body builders who had never taken steroids (nonusers), and a group of 18 healthy sedentary subjects (controls). During the period of steroid administration, there was a slight reduction in total serum cholesterol, with a marked cholesterol decrease in the high-density lipoprotein (HDL) subfractions HDL2 and HDL3, and a significant reduction in the HDL2 cholesterol/HDL3 cholesterol ratio; the percentage of serum cholesterol transported by low-density lipoproteins (LDL) increased significantly. In addition, a marked apoprotein (apo) A-I reduction in the HDL2 and HDL3 subfractions was observed, as well as an apo A-II decrease that was significant only in the HDL3 subfraction, with an A-I/A-II ratio significantly reduced in both subfractions. Serum apo B was only slightly increased, with a very high B/A-I ratio. Apolipoprotein C-II and E levels showed no modifications, while apo C-III reduced significantly. Lipid and apoprotein values returned to almost normal levels in the OFF treatment period. Findings in the group of nonusers were similar to those in sedentary subjects. These results indicate that anabolic steroids profoundly alter the serum lipid-protein profile, and the changes may be caused in part by the significant differences observed in apoprotein levels. PMID- 2105437 TI - Magnetic resonance imaging. PMID- 2105438 TI - Progress toward achieving the 1990 Objectives for the Nation for sexually transmitted diseases. PMID- 2105439 TI - Pertussis surveillance--United States, 1986-1988. PMID- 2105440 TI - Herpes gladiatorum at a high school wrestling camp--Minnesota. PMID- 2105441 TI - Pneumococcal endophthalmitis after ocular surgery--Alaska, California. PMID- 2105442 TI - Anemia during pregnancy in low-income women--United States, 1987. PMID- 2105443 TI - Update: acquired immunodeficiency syndrome--United States, 1989. PMID- 2105444 TI - Clinical spectrum of eosinophilia-myalgia syndrome--California. PMID- 2105445 TI - Transmission of Plasmodium vivax malaria--San Diego County, California, 1988 and 1989. PMID- 2105446 TI - Prevalence of arthritic conditions--United States, 1987. PMID- 2105447 TI - Alzheimer disease--California, 1985-1987. PMID- 2105448 TI - Legionnaires' disease outbreak associated with a grocery store mist machine- Louisiana, 1989. PMID- 2105449 TI - Estimates of HIV prevalence and projected AIDS cases: summary of a workshop, October 31-November 1, 1989. PMID- 2105450 TI - Occupational disease surveillance: occupational asthma. PMID- 2105451 TI - Public Health Service statement on management of occupational exposure to human immunodeficiency virus, including considerations regarding zidovudine postexposure use. PMID- 2105452 TI - Effects of testosterone and growth hormone treatment on hepatic microsomal P450 expression in the diabetic rat. AB - The profile of hepatic microsomal cytochrome P450 expressed in the male and female rat was dramatically altered by streptozotocin-induced diabetes. In the diabetic male, P450 forms IIC11, IIC13, IIA2, and IIIA2 were suppressed and forms IIA1 and IIC12 were induced to the levels observed in the immature male rat. A 6- to 8-fold induction of P450 IIE1 was detected in both male and female diabetic rats. A member of the P450 IIIA family was also induced in the diabetic female rat. Accompanying the change in P450 profile in the diabetic male rat was reduction in circulating testosterone and tetraiodothyronine concentrations and a sharp diminution of the normally pulsatile pattern of growth hormone secretion. In contrast to the male rat, the growth hormone secretion pattern in the diabetic female rat was unchanged from control. The hormone and P450 profiles detected in the diabetic male rat suggest a reversion to an immature physiological state. Testosterone replacement treatments carried out for 2 weeks slightly but significantly affected the suppression of P450 IIC11 and reversed the changes in P450 IIA2, IIIA2, and IIC12 in the diabetic male, without altering the suppressed state of growth hormone secretion. However, 1 week of human growth hormone, administered intravenously every 4 hr to diabetic male rats, failed to significantly reverse the diabetes-induced changes in hepatic cytochromes P450, in particular forms IIC11 and IIE1, despite the presence of an episodic plasma hGH profile. An induction of P450 IIE1 in diabetic female rats, without a reduction in growth hormone secretion, suggests that its induction in diabetes in both sexes is not related to changes in growth hormone. In addition, the results of testosterone treatment on the expression of IIC12, IIA2, and IIIA2 in the diabetic male rat suggest a regulatory role for this hormone that does not involve the pituitary secretion of growth hormone. However, the lack of effect of human growth hormone treatment in the diabetic male on levels of individual P450 forms indicates that in diabetes there may be a change in the ability of the male rat hepatocyte to respond to a somatic signal, possibly as a result of the changes in other hormone factors. PMID- 2105453 TI - Stoichiometry of G protein subunits affects the Saccharomyces cerevisiae mating pheromone signal transduction pathway. AB - The Saccharomyces cerevisiae GPA1, STE4, and STE18 genes encode products homologous to mammalian G-protein alpha, beta, and gamma subunits, respectively. All three genes function in the transduction of the signal generated by mating pheromone in haploid cells. To characterize more completely the role of these genes in mating, we have conditionally overexpressed GPA1, STE4, and STE18, using the galactose-inducible GAL1 promoter. Overexpression of STE4 alone, or STE4 together with STE18, generated a response in haploid cells suggestive of pheromone signal transduction: arrest in G1 of the cell cycle, formation of cellular projections, and induction of the pheromone-inducible transcript FUS1 25 to 70-fold. High-level STE18 expression alone had none of these effects, nor did overexpression of STE4 in a MATa/alpha diploid. However, STE18 was essential for the response, since overexpression of STE4 was unable to activate a response in a ste18 null strain. GPA1 hyperexpression suppressed the phenotype of STE4 overexpression. In addition, cells that overexpressed GPA1 were more resistant to pheromone and recovered more quickly from pheromone than did wild-type cells, which suggests that GPA1 may function in an adaptation response to pheromone. PMID- 2105454 TI - The Adh gene promoters of Drosophila melanogaster and Drosophila orena are functionally conserved and share features of sequence structure and nuclease protected sites. AB - The sibling species Drosophila melanogaster and D. orena show similar patterns of alcohol dehydrogenase expression, both spatially and temporally. These two species diverged from a common ancestor 6 million to 15 million years ago, and the DNA sequences of the promoter regions of their Adh genes show a mosaic pattern of conservation and change. By interspecific transformation of D. orena sequences into D. melanogaster, we demonstrate a functional equivalence between these sequences. Using both D. melanogaster embryo extracts and purified transcription factor Adf-1, we compare the protection of these promoter sequences from nuclease, demonstrating considerable conservation. PMID- 2105456 TI - The GLI gene encodes a nuclear protein which binds specific sequences in the human genome. AB - The GLI gene is amplified in a subset of human tumors and encodes a protein product with five zinc finger DNA-binding motifs. In this study, we show that the GLI gene product has a predominantly nuclear localization and binds DNA in a sequence-specific fashion. Three GLI binding sites were identified by using a novel procedure in which total human DNA was bound to a GLI recombinant fusion protein, and the polymerase chain reaction was used to amplify and recover the bound sequences. The GLI protein protected a 23- to 24-base region within all three binding sites, and the protected region in each case included the 9-base pair sequence 5'-GACCACCCA-3'. One of the binding sites was contained within a 63 base-pair repeat of the variable number of tandem repeat type, whereas the other two sites were represented once in the genome. The approach used here to identify GLI binding sites should be applicable to the characterization of other zinc finger proteins. PMID- 2105455 TI - Sequence elements required for activity of a murine major histocompatibility complex class II promoter bind common and cell-type-specific nuclear factors. AB - We have examined the sequence elements and corresponding DNA-binding factors required for transient expression of the A alpha d promoter fused to the bacterial chloramphenicol acetyltransferase reporter gene in a variety of cultured cell lines. Deletion analysis demonstrated that only about 110 nucleotides of sequence 5' of the transcription start site are required for constitutive expression in the murine B-lymphoma cell line A20 or for gamma interferon-induced expression in the murine monocytic cell line WEHI-3. Linker scanner mutation of this region indicated that at least three sequence elements are required for promoter activity. These elements correspond to the conserved sequence elements found in other human and mouse class II genes, the X box, the Y box, and the H box. Analysis of DNA-binding activity showed that the three most predominant factors present in extracts from WEHI-3, A20, or L cells (which do not express the class II genes) are actually a family of factors that bind to a fourth sequence element, overlapping the 3' end of the X-box sequence, that is homologous to the cyclic AMP-responsive enhancer element. A single common factor that binds to the Y box was detected in extracts from all cells tested, as has been seen with the Y-box elements of other class II genes. Another common factor was found that binds to the more conserved 5' region of the X-box element, although A20 extracts contained a second, distinct binding activity for this region. A common binding factor for the H-box element was detected in extracts from WEHI-3 and L cells. However, this activity was absent in A20 cell extracts. Instead, two different H-box-binding activities were detected, suggesting that different components are involved in class II gene expression in B cells and macrophages. Finally, gamma interferon treatment did not significantly alter the DNA-binding activity in WEHI-3 cells for any of the sequence elements shown to be required for induced chloramphenicol acetyltransferase expression. PMID- 2105457 TI - Mouse Zfx protein is similar to Zfy-2: each contains an acidic activating domain and 13 zinc fingers. AB - The Zfy gene is located on the Y chromosome of placental mammals and encodes a zinc finger protein which may serve as the primary sex-determining signal. A related gene, Zfx, is similarly conserved on the X chromosome. Unlike that in most mammals, the mouse genome contains four homologous zinc finger loci: Zfy-1, Zfy-2, Zfx, and Zfa (on an autosome). We report that, in contrast to the mouse Zfy genes, Zfx is widely transcribed in embryos, newborns, and adults, both male and female. Moreover, Zfx transcripts contain long 3' untranslated sequences which are phylogenetically conserved. Zfa is a processed gene derived from Zfx. An analysis of cDNA clones demonstrated that Zfx encodes a 799-amino-acid protein that is 70% identical to the mouse Zfy-1 and Zfy-2 proteins. Zfx, Zfy-1, and Zfy 2 contain highly acidic amino-terminal domains and carboxy-terminal regions containing 13 zinc fingers. When fused to the DNA-binding domain of GAL4, the acidic domains of Zfx and Zfy-2 activated transcription in yeast cells. PMID- 2105458 TI - DNA-mediated gene transfer into adult rat hepatocytes in primary culture. AB - Proliferation-competent and differentiation-competent adult rat hepatocytes in primary culture were investigated for their ability to express reporter genes (firefly luciferase, bacterial chloramphenicol acetyltransferase, and bacterial beta-galactosidase) driven by tumor virus or eucaryotic promoters that vary in transcriptional efficiency and tissue specificity. Supercoiled plasmid DNA molecules were introduced into the cells by the calcium phosphate coprecipitation protocol of C. Chen and H. Okayama (Mol. Cell. Biol. 7:2745-2752, 1987). Reporter gene expression was virtually restricted to hepatocytes and was efficient (2 to 20% of the cells). The patterns and absolute levels of reporter gene expression depended on assay conditions employed (plasmid concentration [optimal at 2.4 micrograms of DNA per ml] and duration of exposure [optimal between 5 and 10 h]), culture growth cycle stages (lag, log, or stationary phase), properties and tissue specificity of the promoter(s) tested, and composition (and timing of fluid change) of the culture medium with or without the hepatocyte mitogen human transforming growth factor-alpha. Initial observations suggest that during hepatocellular growth transitions, human transforming growth factor-alpha differentially regulates exogenously introduced promoters associated with hepatocyte-specific function and proliferation. These findings provide a simple, fast, and powerful approach to analyzing the molecular and cellular biology of hepatocyte growth control. PMID- 2105459 TI - Mutational analysis of the DRA promoter: cis-acting sequences and trans-acting factors. AB - Class II major histocompatibility genes are expressed at high levels in B lymphocytes and are gamma interferon (IFN-gamma) inducible in many other cells. Previously, we observed that DRA promoter sequences from positions -150 to +31 determine the tissue specificity of this class II gene. Moreover, Z and X boxes located between positions -145 and -87 conferred B-cell specificity and IFN-gamma inducibility upon a heterologous promoter. In this study, sequences from positions -145 to -35 in the DRA promoter were systematically mutated by using oligonucleotide cassettes. Z (-131 to -125), pyrimidine (-116 to -109), X (-108 to -95), Y (-73 to -61), and octamer (-52 to -45) boxes were required for B-cell specificity and, with the exception of the octamer box, for IFN-gamma inducibility. Z box and sequences flanking Z and X boxes helped to determine low levels of expression in T and uninduced cells. In phenotypically distinct cells, shared and distinct proteins bound to these conserved upstream sequences. However, few correlations between expression and DNA-binding proteins could be made. Similar proteins bound to Z and X boxes, and the Z box most likely represents a duplication of the X box. PMID- 2105460 TI - Adaptive resistance of Saccharomyces cerevisiae to chronic treatment with mutagens being due to a dominant mutation. AB - The exposure of mammalian cells or tumors for weeks or months to low non-lethal doses of cytostatic drugs may induce multi-drug resistance, which can be enhanced by a variety of DNA-damaging agents. In yeast multi-drug resistance to a variety of drugs has been observed. DNA-damaging agents have not yet been tested. As the appearance of resistance is the result of long-term exposure, we decided to extend the application of test substances to a period of up to 400 days. In such long-term experiments S. cerevisiae MP1 adapted to treatment with low doses of mutagens. Consistent results were obtained for both alkylating and non-alkylating mutagenic substances. Furthermore, the adaptive resistance to the alkylating agent also adapted cells to the non-alkylating agent, which implies that there may be a single pathway for mutagens with different modes of action. Random spore analysis of adapted yeast cells and the back-cross to the parental wild type indicates that a single dominant mutation is responsible for the adaptive resistance. PMID- 2105461 TI - Isolation of a Bacillus subtilis mutant defective in constitutive O6-alkylguanine DNA alkyltransferase. AB - A mutant of Bacillus subtilis defective in the constitutive activity of O6 alkylguanine-DNA alkyltransferase was isolated from a strain (ada-1) deficient in the adaptive response to DNA alkylation. Cells carrying the mutation dat-1 which was responsible for the defect in constitutive activity exhibited hypersensitivity for lethality and mutagenesis when challenged with methyl nitroso compounds. The constitutive activity is independent of the adaptive response, and seems to function as a basal defense against environmental alkylating agents. PMID- 2105462 TI - X-ray sensitivity and single-strand DNA break repair in mutagen-sensitive mutants of Drosophila melanogaster. AB - Mutants of Drosophila melanogaster that are sensitive to chemical mutagens were analyzed for sensitivity to X-rays and for the capacity to repair single-strand DNA breaks induced by X-rays. Analysis of X-ray sensitivity demonstrated that 74% of the mutants assayed display some X-ray sensitivity, with 75% of the sensitive lines being extremely sensitive. Repair of single-strand breaks was assayed after both high and low doses of irradiation in order to permit detection of repair over a wide range of damage. The results of this investigation fail to show a correlation between X-ray sensitivity and this particular repair process. Repair of single-strand breaks is therefore mediated by repair processes unrelated to those that are disrupted in the current mutant collection. PMID- 2105463 TI - Sensitivity to ether anesthesia and to gamma-rays in mutagen-sensitive strains of Drosophila melanogaster. AB - An ether-resistant strain of Drosophila melanogaster, Eth-29, has previously been found to be radiosensitive. Some mutagen-sensitive strains are known to be hypersensitive to X-rays in larvae. The correlation between sensitivities to ether anesthesia and to gamma-rays was examined in adult flies of 12 mutagen sensitive strains and 6 control strains. A wide variation in sensitivities to ether anesthesia, gamma-ray knock-down and gamma-ray lethality was demonstrated. No correlation between DNA-repair capacity and ether sensitivity or gamma-ray knock-down sensitivity was shown. Only mei-9 and mus201, which are deficient in excision repair, as well as Eth-29 were found to be sensitive to gamma-ray lethality. These findings indicate that the targets for ether anesthesia, knock down and lethality may be different. Lethality appears to be caused by DNA damage, while the other 2 endpoints appear not to be related to DNA damage. PMID- 2105464 TI - Differential sensitivity of peripheral blood lymphocytes of untreated leprosy patients to mitomycin C. AB - The effects of a bifunctional alkylating agent mitomycin C (MMC), an effective inducer of chromosome aberrations and sister-chromatid exchanges (SCEs), have been studied in untreated leprosy patients. This was done to study the mutagen sensitivity of the leprosy patients. The frequency of chromosomal aberrations induced by MMC (conc. 0.01 microgram/ml) was 2.5% in controls, 3.6% in paucibacillary (PB), and 6.8% in multibacillary (MB) patients. The difference in the frequency of MMC-induced chromosome aberrations between the 3 groups studied was highly significant (p less than 0.01). Cultures grown with MMC showed the frequency of SCEs/cell to be 12.70 +/- 1.19 in controls, 19.97 +/- 3.51 in PB, and 29.66 +/- 5.92 in MB patients. The differences in the frequency of MMC induced SCEs between the 3 groups were found to be highly significant (p less than 0.01). The enhanced frequencies of spontaneous and MMC-induced chromosome aberrations and SCEs observed in PB and MB patients indicate a clear differential mutagen sensitivity between PB and MB patients who are known to have different immunological status and thereby differ in the severity of the disease. PMID- 2105465 TI - Genotoxicity of p-aminophenol in somatic and germ line cells of Drosophila melanogaster. AB - p-Aminophenol (PAP; as a component of, e.g., hair dyes, photographic developers, as adsorbent in gas filters, as a metabolite of various fungicides, pesticides and drugs) has been tested for genotoxicity in Drosophila by means of the sex linked recessive lethal test (SLRLT) and the somatic mutation and recombination test (SMART) of the wing. While the SLRLT was not significant, the SMART clearly indicated that the compound has genotoxic properties in this in vivo test in agreement with a majority of mammalian short-term tests in vitro and in vivo. The reducing agent dithiothreitol enhanced the genotoxic effects of PAP in the SMART; the reasons for this interaction remain to be elucidated. PMID- 2105466 TI - The effect of valproic acid on SCE and chromosome aberrations in epileptic children. AB - Sister-chromatid exchange (SCE) and chromosome aberrations have been studied in peripheral lymphocytes of 20 epileptic children treated in monotherapy with valproic acid (VPA) for 6-52 months and in 2 matched control groups. The frequencies of SCE in the VPA-treated epileptic children were significantly higher than in the 2 control groups (p less than 0.01); rates of chromosome aberrations were slightly higher but not significantly different from the 2 control groups. We also examined SCE in 10 epileptic children before and after they took sodium valproate for 6-7 months; there was a statistically significant change in SCE following VPA. 9 normal children whose lymphocytes were exposed in vitro to sodium valproate (5-20 micrograms/ml) showed a significant increase in SCE. PMID- 2105467 TI - Indications of an adaptive response in C57BL mice pre-exposed in vivo to low doses of ionizing radiation. AB - C57BL/6 mice were whole-body irradiated with 5 cGy/day ('adapting dose') on 4 consecutive days and their spleens removed on day 1, 3, 7, 12, 19 or 26 after the last irradiation. In vitro UV-light-induced unscheduled DNA synthesis (UDS) and mitomycin C (MMC)-induced sister-chromatid exchanges (SCEs) were scored in lymphocytes (UV-light and MMC being the 'challenging agents'), yielding higher UDS values and lower frequencies of induced SCEs than cells of non-adapted animals. On day 12 this effect could only be seen in half, on days 19 and 26 in none of the performed experiments. The results support those published by Tuschl et al. (1980, 1983) and Liu et al. (1987), showing that it is possible to induce the adaptive response in vivo. PMID- 2105468 TI - Drug approval: product licensing by phone. PMID- 2105469 TI - Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons. AB - Neurons in culture can have fundamentally distinct morphologies which permit their cytological identification and the recognition of their neurites as axons or dendrites. Microtubules may have a role in determining morphology by the selective stabilization of spatially distinct microtubule subsets. The plasticity of a neurite correlates inversely with the stability of its component microtubules: microtubules in growth cones are very dynamic, and in initial neurites there is continuous incorporation of labelled subunits, whereas in mature neurites, microtubules are highly stabilized. The binding of microtubule associated proteins to the microtubules very probably contributes to this stability. Cerebellar neurons in dissociated culture initially extend exploratory neurites and, after a relatively constant interval, become polarized. Polarity becomes evident when a single neurite exceeds the others in length. These stable neurites cease to undergo the retractions and extensions characteristic of initial neurites and assume many features of axons and dendrites. We have now studied the role of the neuronal microtubule-associate protein tau in neurite polarization by selectively inhibiting tau expression by the addition of antisense oligonucleotides to the culture media. Although the extension of initial exploratory neurites occurred normally, neurite asymmetry was inhibited by the failure to elaborate an axon. PMID- 2105470 TI - Structural biology. Putting a twist in the tale. PMID- 2105472 TI - Paternal origin of new mutations in von Recklinghausen neurofibromatosis. AB - Von Recklinghausen neurofibromatosis (NF-1) is a common autosomal dominant disorder. The estimated new mutation rate (1 x 10(-4] is one of the highest for a human disorder. Here we report that in 12 of 14 families we have analysed, the new mutation is of paternal origin. This result is similar to that recently obtained for retinoblastoma. In other genetic disorders that show a bias towards paternal origin of new mutations, there is a marked increase in the incidence of mutations with paternal age, consistent with the mutations arising from replication errors in mitosis of spermatogonial stem cells. In retinoblastoma and NF-1, however, such paternal age effects are slight or absent. The mechanism or timing of germline mutation could therefore be different in the two cases. PMID- 2105471 TI - Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. AB - Mutations in the period (per) gene of Drosophila melanogaster affect both circadian and ultradian rhythms. Levels of per gene product undergo circadian oscillation, and it is now shown that there is an underlying oscillation in the level of per RNA. The observations indicate that the cycling of per-encoded protein could result from per RNA cycling, and that there is a feedback loop through which the activity of per-encoded protein causes cycling of its own RNA. PMID- 2105474 TI - Is tube feeding artificial life support? PMID- 2105473 TI - An interview with Senator David H. Pryor. AB - As Chairman of the Senate Special Committee on Aging, Sen. David H. Pryor (D-AR) is tackling the serious health care dilemmas facing senior citizens. In this interview with Nursing Economic+, Sen. Pryor offers his views on the urban-rural hospital differential, nursing home care, long-term care, and prescription drugs. PMID- 2105475 TI - Metabolic response to enteral food in different phases of cancer cachexia in rats. AB - The resting energy expenditure (REE) and postprandial energy expenditure (PPEE) were measured using closed-circuit indirect calorimetry in Walker 256 carcinosarcoma-bearing rats. The results were compared to the appropriate controls. The PPEE measurements were performed after oral test feeding. At the beginning of the tumor growth, the REE and PPEE were similar in all groups. In the second week, the tumor-bearing rats showed increased REE and decreased PPEE. The tumor-bearing rats lost weight and became anorectic. After day 14, the REE rapidly dropped to very low values and the body weight continued to decrease. This study makes it possible to differentiate three phases of cancer cachexia: silent or preclinical, hypermetabolic and hypometabolic. PMID- 2105476 TI - [Hemorrheologic parameters in myocardial infarct during the hospitalization phase]. AB - The changes of the rheological parameters (whole blood and plasma viscosity, fibrinogen level, red cell count, hematocrit) of 22 AMI patients (mean age: 59 years) were studied during the hospital phase of acute myocardial infarction. The measurements were carried out after the admission, after the beginning of the mobilization and before the discharge from the hospital. Looking at the results of all of the patients they could not find any statistically significant change, although in the first phase improving hemorheological parameters were measured and this way the discharge values were similar to the admission ones. In men significantly worse starting values were found than in women and the deterioration of these parameters in their group was also expressed. The deliberate use of diuretics and the administration of high dose nitroglycerin may be one part of the less worsening rheological parameters in comparison with the literature. PMID- 2105477 TI - [A rapid test for the analysis of lactase and sucrase activity in the jejunum (a comparative study)]. AB - Jejunal lactase and sucrase activities were demonstrated in biopsy specimens obtained endoscopically using a rapid test which had been developed previously. The results were compared with enzyme activities determined by Dahlquist's method. The data suggest that the rapid test is suitable for the demonstration about the presence of lactase and sucrase, and the results are correlated with enzyme activities measured by assay. The main advantage of the test, that it is rapid, simple and cheap, no special equipments are necessary, so it can be used in every endoscopic department. PMID- 2105478 TI - Aspergillar osteomyelitis of the acetabulum. A case report and review of the literature. AB - An unusual case of primary osteomyelitis of the acetabulum caused by Aspergillus flavus in a presumed immunocompetent adult is presented. Review of the literature found 25 additional cases of aspergillar osteomyelitis, which occurred predominantly in hosts with either inborn or acquired immune defects. There were notable differences between the adult and the pediatric cases in causation, clinical presentation, and treatment regimens. In children, the underlying cause was usually severe immunocompromise; among adults, the majority of cases occurred in hosts presumed to be immunocompetent. In all but one case, the children were treated with antifungal chemotherapy alone, whereas the adult patients nearly always received surgical debridement in conjunction with chemotherapy. PMID- 2105479 TI - Cefaclor treatment of upper and lower respiratory tract infections caused by Moraxella catarrhalis. AB - A retrospective analysis of data from 18 clinical studies was performed to examine the effectiveness and safety of cefaclor in the treatment of upper and lower respiratory tract infections caused by Moraxella catarrhalis (previously called Branhamella catarrhalis). Eighty-six percent of 56 evaluable patients had improvement in their symptoms of infections following therapy with cefaclor. There were no serious or life-threatening adverse drug experiences reported by any patient. Cefaclor appears to be an appropriate antibiotic for the safe and effective treatment of respiratory tract infections caused by M. catarrhalis. PMID- 2105480 TI - Listeria meningitis in infants and children. PMID- 2105481 TI - [Diagnosis in low prevalence of disease. Significance of specificity rather than sensitivity in sequencing of diagnostic tests]. AB - The significance of specificity rather than sensitivity for the sequence of diagnostic tests is discussed. The rule of thumb states that when the prevalence of disease is low it is advisable to save time and money by eliminating as many healthy individuals as possible from the test system. PMID- 2105482 TI - Management of myelosuppression in the patient with cancer. AB - Bone marrow depression (myelosuppression) in the patient with cancer may result from the disease itself or from its treatment. The consequences of myelosuppression are numerous; the most critical problem that results from leukopenia is infection. Serious clinical consequences follow depression of normal leukocyte function. A clear understanding of the functioning of each type of leukocyte is essential for managing the various complications associated with leukopenia. The three components of myelosuppression management are: prevention of infection, frequent patient assessment for the early detection of infection, and aggressive management when such infection arises. The oncology nurse minimizes patient- and environment-related sources of infection and is aware that detection is complicated by the lack or diminution of signs and symptoms in a leukopenic patient. Infections that arise are managed in different ways, depending on the pathogen and on available therapy. In addition to conventional antimicrobial therapy, newer therapeutic modalities, such as colony-stimulating factors, may hold promise for the treatment of leukopenic patients. The nurse is responsible for many aspects of the care for these patients. PMID- 2105483 TI - Nursing protocol for the patient with neutropenia. AB - Although major advances in the treatment of cancer have resulted in improved survival rates, serious infections continue to be a major source of morbidity and mortality in the immunocompromised patient. Patients may experience prolonged periods of bone marrow suppression accompanied by neutropenia as a result of the underlying disease, and as a result of treatment with myelosuppressive chemotherapy, intensive radiotherapy, or both. Neutropenia is the single most important factor predisposing patients with cancer to infection. The risk of developing infection increases as neutropenia persists, and this risk is consistently greater at lower neutrophil levels. Infection in a patient with neutropenia is regarded as an emergency situation requiring immediate action; progression of localized to disseminated infection leading to sepsis may be so rapid that, if not detected early, mortality is high. In the presence of neutropenia, the manifestation of infection leading to life-threatening septicemia is altered. The usual signs and symptoms of infection may be minimal or absent, hindering early and accurate diagnosis of infection. To provide a means of early and more accurate diagnosis of infection in the patient with neutropenia, a nursing protocol has been developed that incorporates preventive interventions, guidelines for early detection of impending infection, and measures to control infection. PMID- 2105484 TI - Economies of scale, physician volume for orthopedic surgical patients, and the DRG prospective payment system. AB - American hospitals face increasing constraints due to a variety of factors. Federal and state diagnostic-related group (DRG) prospective hospital pricing has caused tremendous fiscal pressure on hospitals; many face substantial financial deficits. We analyzed the volume of orthopedic surgical procedures performed by an individual orthopedic surgeon for all patients (N = 2,134) treated for a 3 year period at a large academic medical center; these surgeons were arbitrarily divided into low volume or high volume. Patients of low volume surgeons had a longer hospital length of stay and hospital cost (after correction for DRG case mix and severity of illness), greater financial risk under DRGs, and a poorer outcome, compared with patients of higher volume orthopedic surgeons. Pearson correlation showed an inverse relationship between cost per patient and physician volume for nonemergency patients -0.201 (P less than .0001), and emergency patients, -0.321 (P less than .0001). Although the reasons for these findings appeared multifactoral, they raise important issues related to orthopedic surgical hospital costs, access, and quality of care. In addition, they suggest that hospital cost for these patients (and perhaps outcome) may be related to orthopedic surgical volume, and that DRG hospital payment (on the margin) may affect future orthopedic surgical practice opportunities. PMID- 2105485 TI - Compartment syndrome of the triceps as a complication of thrombolytic therapy. PMID- 2105486 TI - Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumor progression. AB - A number of mouse skin tumors initiated by the carcinogens N-methyl-N'-nitro-N nitrosoguanidine (MNNG), methylnitrosourea (MNU), 3-methylcholanthrene (MCA), and 7,12-dimethylbenz[a]anthracene (DMBA) have been shown to contain activated Ha-ras genes. In each case, the point mutations responsible for activation have been characterized. Results presented demonstrate the carcinogen-specific nature of these ras mutations. For each initiating agent, a distinct spectrum of mutations is observed. Most importantly, the distribution of ras gene mutations is found to differ between benign papillomas and carcinomas, suggesting that molecular events occurring at the time of initiation influence the probability with which papillomas progress to malignancy. This study provides molecular evidence in support of the existence of subsets of papillomas with differing progression frequencies. Thus, the alkylating agents MNNG and MNU induced exclusively G ---- A transitions at codon 12, with this mutation being found predominantly in papillomas. MCA initiation produced both codon 13 G ---- T and codon 61 A ---- T transversions in papillomas; only the G ---- T mutation, however, was found in carcinomas. These findings provide strong evidence that the mutational activation of Ha-ras occurs as a result of the initiation process and that the nature of the initiating event can affect the probability of progression to malignancy. PMID- 2105487 TI - Activation of the pp60c-src protein kinase is an early event in colonic carcinogenesis. AB - Colonic neoplasia provides an opportunity to study tumor progression because most carcinomas arise from adenomas (polyps), which, in turn, arise from normal epithelia. The malignant potential of adenomas varies with size, histology, and degree of dysplasia. Polyps that are less than 2 cm with villous architecture and severe dysplasia are most likely to contain carcinoma. Previous studies demonstrated that the in vitro protein-tyrosine kinase activity of pp60c-src from colon carcinomas is significantly higher than that from adjacent normal mucosa. Here we report that the protein kinase activity of pp60c-src is also elevated in colonic polyps. Activity is highest in malignant polyps and in greater than 2-cm benign polyps that contain villous structure and severe dysplasia. Thus, pp60c src activation occurs in benign polyps that are at greatest risk for developing cancer. These data suggest that activation of the protooncogene product pp60c-src may be an important event in the genesis of human colon carcinoma. PMID- 2105488 TI - Myristoylation of an inhibitory GTP-binding protein alpha subunit is essential for its membrane attachment. AB - We transfected COS cells with cDNAs for the alpha subunits of stimulatory and inhibitory GTP-binding proteins, alpha s and alpha i1, respectively, and immunoprecipitated the metabolically labeled products with specific peptide antibodies. Cells were separated into particulate and soluble fractions before immunoprecipitation; [35S]methionine-labeled alpha s and alpha i were both found primarily in the particulate fraction. [3H]Myristate was incorporated into endogenous and transfected alpha i but could not be detected in alpha s even when it was overexpressed. We converted the second residue, glycine, of alpha i1 into alanine by site-directed mutagenesis. Upon transfection of the mutant alpha i1 into COS cells, the [35S]methionine-labeled product was localized primarily to the soluble fraction, and, also unlike normal alpha i1, the mutant failed to incorporate [3H]myristate. The unmyristoylated mutant alpha i1 could still interact with the beta-gamma complex, since purified beta gamma subunits promoted pertussis toxin-catalyzed ADP-ribosylation of both the normal and mutant alpha i1 subunits. These results indicate that myristoylation is critical for membrane attachment of alpha i but not alpha s subunits. PMID- 2105489 TI - Regulation of interleukin 3 mRNA expression in mast cells occurs at the posttranscriptional level and is mediated by calcium ions. AB - Interleukin 3 (IL-3) is transiently produced by murine bone marrow-derived mast cells in response to antigen stimulation of the high-affinity immunoglobulin E receptors. We have studied the postreceptor signaling pathways involved in regulating expression of the IL-3 gene in the murine mast cell line PB-3c. Large amounts of IL-3 mRNA accumulated after exposure of cells to calcium ionophore A23187, a reagent that increases intracellular Ca2+. Phorbol 12-myristate 13 acetate, which stimulates protein kinase C, did not induce IL-3 mRNA accumulation, although it did potentiate the effect of A23187. Nuclear run-on analysis showed that the IL-3 gene is constitutively transcribed in unstimulated cells and that treatment with A23187 and/or phorbol ester has no influence on its transcription rate. The effect of A23187 was found to be due to stabilization of the IL-3 mRNA. In cells maintained in the presence of A23187 the IL-3 mRNA was stable during 3 hr of incubation with actinomycin D, whereas removal of A23187 under the same conditions resulted in rapid degradation of the mRNA. These results indicate that control of expression of the IL-3 gene in mast cells is primarily at the posttranscriptional level and that the Ca2(+)-dependent signal transduction pathway plays an important role in this process. Synthesis of granulocyte/macrophage colony-stimulating factor mRNA in response to A23187 and phorbol ester was found to be subject to both transcriptional and posttranscriptional regulation. PMID- 2105490 TI - Complete nucleotide sequence of an immunoglobulin heavy-chain gene and analysis of immunoglobulin gene organization in a primitive teleost species. AB - The immunoglobulin heavy-chain variable region (VH) locus in a phylogenetically primitive teleost (Elops saurus) has been characterized by a strategy that relied initially on cross-hybridization between genomic VH segments and a murine VH probe. Using a homologous (Elops) VH probe and DNA sequencing, this gene family has been shown to be complex and to contain overt pseudogenes. A homologous probe also has been used to isolate a full copy length cDNA containing constant (CH) as well as joining (JH) and VH regions. Genomic analyses using CH-, JH-, and VH specific probes have demonstrated the presence of only a single hybridizing CH and several JH elements. JH-CH linkage is less than or equal to 3.6 kilobases (kb) and VH-CH linkage is less than or equal to 100 kb, as estimated by field inversion gel electrophoresis. An additional VH family sharing less than 50% nucleotide identity with the prototype Elops VH sequence is described. Taken together, these results suggest that the immunoglobulin VH locus in a comparatively primitive teleost resembles the VH locus in mammals, but not that found in the more phylogenetically distant elasmobranchs. The evolutionary radiations of cartilaginous and bony fishes are associated with a dramatic change in the organization and, presumably, regulation of immunoglobulin genes. The origins of the modern VH gene locus can be traced to the primitive teleost fishes. PMID- 2105491 TI - Twenty Drosophila visual system cDNA clones: one is a homolog of human arrestin. AB - From a group of 436 Drosophila melanogaster cDNA clones, we selected 39 that are expressed exclusively or predominantly in the adult visual system. By sequence analysis, 20 of the clones appear to represent previously unreported distinct cDNAs. The corresponding transcripts are detected in the retina and optic lobes. The genes are scattered throughout the genome, some near mutations known to affect eye function. One of these clones has been identified, by sequence analysis, as the structural gene (Arr) for a Drosophila homolog of human arrestin. Vertebrate arrestin interacts with rhodopsin in phototransduction and has been associated with an autoimmune form of uveitis in primates. The presence of an arrestin homolog in Drosophila suggests that both the vertebrate and invertebrate phototransduction cascades are regulated in a similar manner. PMID- 2105492 TI - Expression and purification of the leucine zipper and DNA-binding domains of Fos and Jun: both Fos and Jun contact DNA directly. AB - The protein products of the fos and jun protooncogenes interact cooperatively in the form of a heterodimer with the activator protein 1 (AP-1) regulatory element. To characterize the properties of these proteins, we have expressed polypeptides comprised of the dimerization and DNA-binding domains of Fos and Jun in Escherichia coli. The mini-Fos (wbFos) and the mini-Jun (wbJun) proteins were purified to apparent homogeneity by using a nickel affinity chromatography procedure. Purified wbFos and wbJun associated rapidly in vitro and interacted cooperatively with the human metallothionein IIA AP-1-binding site. However, efficient DNA binding of wbJun and wbFos-wbJun complexes required an additional activity present in nuclear extracts. This activity was sensitive to alkylating agents and could be partially mimicked by the presence of reducing and stabilizing agents. DNase I footprinting experiments demonstrated that Jun homodimeric complexes and Fos-Jun heterodimeric complexes interacted with the same site on the human metallothionein IIA gene. Moreover, UV-crosslinking studies demonstrated that Fos and Jun contact DNA directly and that both proteins interacted equivalently with either strand of the AP-1-binding site. PMID- 2105493 TI - In vivo properties of colicin A: channel activity is voltage dependent but translocation may be voltage independent. AB - The kinetics of K+ efflux caused by colicin A in Escherichia coli-sensitive cells have been investigated by using a K(+)-selective electrode. The order of magnitude of the rate of K+ efflux per colicin molecule was comparable to that of ion channels. The dependence of K+ efflux upon multiplicity, pH, temperature, and membrane potential (delta psi) was determined. The translocation of colicin A from the outer membrane receptor to the inner membrane and insertion into the inner membrane required a fluid membrane, but once inserted, the channel properties showed little dependence upon the state of the lipids. At a given multiplicity, the lag time before the onset of K+ efflux was found to reflect the time required for translocation and/or insertion of colicin into the cytoplasmic membrane. Opening of the channel only occurred above a threshold value of delta psi of 85 +/- 10 and 110 +/- 5 mV at pH 6.8 and 7.8, respectively. Conditions were designed for closing and reopening of the channel in vivo. These conditions allowed us to test separately the delta psi requirements for translocation and channel opening: translocation and/or insertion did not appear to require delta psi. The channel formed in vivo featured properties similar to that of the channel in lipid planar bilayers. PMID- 2105494 TI - Insulin, oxytocin, and vasopressin stimulate protein kinase C activity in adipocyte plasma membranes. AB - Incubation of isolated rat adipocytes with insulin, vasopressin, or oxytocin increased plasma membrane-bound protein kinase C (PKC) activity by 100-400%. PKC activity was assayed by a procedure that is virtually background-free, thus permitting assay of protein kinase activity in highly diluted samples of solubilized membranes. Hormone-dependent increases in PKC activity were limited to plasma membranes. Stimulation of the kinase was half-maximal with 70 pM insulin, and the hormone effect was rapid. Oxytocin and vasopressin produced effects on PKC similar to insulin, but the magnitude of the vasopressin stimulation exhibited seasonal variations. Treatment of cells with phorbol 12 myristate 13-acetate (PMA) resulted in a loss of PKC activity from the cytosol and a gain in plasma membrane activity, indicative of translocation of the enzyme. With activity measurements it was not possible to determine if insulin stimulated a translocation of the kinase. However, Western blot analysis of plasma membranes with polyclonal antibodies directed against PKC suggest that at least some of the insulin-stimulated PKC activity resulted from enzyme translocation. PMID- 2105495 TI - A rapid method of cloning functional variable-region antibody genes in Escherichia coli as single-chain immunotoxins. AB - We have devised a strategy based on polymerase chain reaction (PCR) for the rapid cloning of functional antibody genes as single-chain immunotoxins. RNA from a hybridoma producing an antibody (OVB3) that reacts with ovarian cancer cells was used as a template to make the first strand of a cDNA. Then a second strand was synthesized and amplified by using two sets of DNA primers that (i) hybridized to the ends of the light- and heavy-chain variable regions, (ii) encoded a linker peptide, and (iii) contained appropriate restriction enzyme sites for cloning. After 30 cycles of PCR, the DNA fragments containing sequences encoding the light and heavy-chain variable regions were cloned into an Escherichia coli expression vector containing a portion of the Pseudomonas exotoxin gene. Clones encoding recombinant single-chain immunotoxins were expressed in E. coli and the protein product was assessed for its ability to bind to or kill cells bearing the OVB3 antigen. By using this approach it should be possible to rapidly clone the functional variable region sequences of many different antibodies from hybridoma RNA. PMID- 2105496 TI - Characterization of c-Ki-ras and N-ras oncogenes in aflatoxin B1-induced rat liver tumors. AB - c-Ki-ras and N-ras oncogenes have been characterized in aflatoxin B1-induced hepatocellular carcinomas. Detection of different protooncogene and oncogene sequences and estimation of their frequency distribution were accomplished by polymerase chain reaction, cloning, and plaque screening methods. Two c-Ki-ras oncogene sequences were identified in DNA from liver tumors that contained nucleotide changes absent in DNA from livers of untreated control rats. Sequence changes involving G.C to T.A or G.C to A.T nucleotide substitutions in codon 12 were scored in three of eight tumor-bearing animals. Distributions of c-Ki-ras sequences in tumors and normal liver DNA indicated that the observed nucleotide changes were consistent with those expected to result from direct mutagenesis of the germ-line protooncogene by aflatoxin B1. N-ras oncogene sequences were identified in DNA from two of eight tumors. Three N-ras gene regions were identified, one of which was shown to be associated with an oncogene containing a putative activating amino acid residing at codon 13. All three N-ras sequences, including the region detected in N-ras oncogenes, were present at similar frequencies in DNA samples from control livers as well as liver tumors. The presence of a potential germ-line oncogene may be related to the sensitivity of the Fischer rat strain to liver carcinogenesis by aflatoxin B1 and other chemical carcinogens. PMID- 2105497 TI - An essential member of the HSP70 gene family of Saccharomyces cerevisiae is homologous to immunoglobulin heavy chain binding protein. AB - Immunoglobulin heavy chain binding protein (BiP) is present in the lumen of the mammalian endoplasmic reticulum, where it associates transiently with a variety of newly synthesized secretory and membrane proteins or permanently with mutant proteins that are incorrectly folded. We describe a unique member of the Saccharomyces cerevisiae 70-kDa heat shock protein gene family (HSP70) that encodes a protein homologous to mammalian BiP. The DNA sequence contains a 2046 nucleotide open reading frame devoid of introns, and examination of the predicted amino acid sequence reveals features not found in most other yeast HSP70 proteins but which are present in BiP. Most notable are a 42-residue sequence at the N terminus that exhibits characteristics of a cleavable signal sequence and a C terminal sequence, -His-Asp-Glu-Leu, that is involved in determining endoplasmic reticulum localization in yeast. The 5' flanking region of this gene contains two overlapping sequences between nucleotides -146 and -169 that closely resemble consensus heat shock elements. The yeast BiP gene is strongly heat shock inducible, whereas the BiP genes in various other species are either weakly or non-heat-inducible. We demonstrate that a functional BiP gene is essential for vegetative growth. An evolutionary comparison of amino acid sequences of 34 HSP70 proteins from 17 species suggests that BiP genes share a common ancestor, which diverged from other HSP70 genes near the time when eukaryotes first appeared. PMID- 2105498 TI - Isoproterenol stimulates shift of G proteins from plasma membrane to pinocytotic vesicles in rat adipocytes: a possible means of signal dissemination. AB - Guanine nucleotide-binding regulatory proteins (G proteins) are linked to a large number of surface membrane receptors and appear to regulate a variety of effector systems located both in the plasma membrane and in other parts of the cell. The mechanism of the disseminative actions of G proteins remains obscure. During an investigation of the fate of two types of G proteins, Gs and Gi, in rat adipocytes, we unexpectedly found that isoproterenol, which stimulates cAMP levels and lipolysis in these cells, induces parallel increases in both Gs and Gi in a low-density microsomal fraction rich in endosomes and Golgi bodies. Two plasma membrane constitutive enzymes, adenylyl cyclase and 5'-nucleotidase, are also elevated in this fraction. NaF and NaN3, metabolic inhibitors, block the redistribution process. The isoproterenol-stimulated shifts are completely reversible after removal of the hormone, indicating a recycling, endocytic process. The endocytic process seems to be fluid phase endocytosis, or pinocytosis, since isoproterenol stimulates the uptake of both fluorescent labeled dextran and horseradish peroxidase into the same vesicles containing Gs. However, the vesicles that accumulate in response to isoproterenol seem heterogenous in properties that may reflect the lipolytic process induced by isoproterenol. It is speculated that the "pinosomes" formed in response to lipolytic hormones may continually produce signals within the cellular interior during their processing and cycling. Hence, signal production in response to hormones need not be confined to the cell membrane; circulating pinosomes may be responsible for some of the disseminative effects of hormones. PMID- 2105499 TI - High-frequency nuclear transformation of Chlamydomonas reinhardtii. AB - By using a method in which cell-wall-deficient Chlamydomonas reinhardtii cells were agitated in the presence of DNA, glass beads, and polyethylene glycol, nuclear transformation rates of approximately 10(3) transformants per micrograms of plasmid DNA were achieved. The nitrate reductase gene from wild-type Chlamydomonas was used to complement a mutation in the corresponding gene of a strain containing nit1-305. Transformants were selected by growth with nitrate as sole source of nitrogen. The transforming DNA integrated into the genome at a low copy number in nit+ transformants. When cells carrying nit1-305 were agitated in the presence of two plasmids, one with the gene for nitrate reductase and the second with an unselected gene, the unselected gene was present in 10-50% of nit+ transformants. This high frequency of cotransformation will allow any cloned gene to be introduced into Chlamydomonas. Moreover, the overall efficiency of transformation should be high enough to permit isolation of genes from genomic libraries by complementation of stable nuclear mutants. The availability of efficient nuclear and chloroplast transformation in Chlamydomonas provides specific advantages for the study of chloroplast biogenesis, photosynthesis, and nuclear-chloroplast genome interactions. PMID- 2105500 TI - Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. AB - We report on the production of tumor necrosis factor (TNF)-alpha and TNF-beta by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of TNF-alpha, whereas DR3- and DR4-positive subjects show high levels of TNF-alpha production. No correlation between TNF-alpha levels and HLA-A, -B, and -C genotype was found. The relevance of this quantitative polymorphism to the genetic predisposition to lupus nephritis in systemic lupus erythematosus (SLE) patients was investigated. DR2, DQw1-positive SLE patients show low levels of TNF alpha inducibility; this genotype is also associated with an increased incidence of lupus nephritis. DR3-positive SLE patients, on the other hand, are not predisposed to nephritis, and these patients have high TNF-alpha production. DR4 haplotype is associated with high TNF-alpha inducibility and is negatively correlated with lupus nephritis. These data may help explain the strong association between HLA-DR2, DQw1 in SLE patients and their susceptibility to nephritis. PMID- 2105501 TI - ADP-ribosylation factor is functionally and physically associated with the Golgi complex. AB - ADP-ribosylation factor (ARF) is a ubiquitous, highly conserved 21-kDa GTP binding protein, first identified in animal cells as the cofactor required for the in vitro ADP-ribosylation of the stimulatory regulatory subunit of adenylate cyclase, Gs, by cholera toxin. As the relevance of this activity to in vivo function is unknown, we have taken advantage of the conserved nature of ARF to study its function in Saccharomyces cerevisiae. Yeast cells bearing an arf1 null mutation display a number of phenotypes suggesting a defect in the secretory pathway. Secreted invertase is only partially glycosylated, and there is a small internal accumulation of invertase. Genetic experiments revealed interactions between ARF1 and other genes known to be involved in the secretory pathway, including YPT1, which encodes a different GTP-binding protein. In accord with these genetic results, immunofluorescence and immunoelectron microscopy show that ARF protein is localized to the Golgi apparatus in mammalian cells, in particular to the cytosolic surface of predominantly cis-Golgi membranes. Together, these results indicate that ARF functions in intracellular protein transport to or within the Golgi apparatus, a role not predicted by the previous in vitro biochemical studies. PMID- 2105502 TI - Photoaffinity labeling of ATP and NAD+ binding sites on recombinant human interleukin 2. AB - Interleukin 2 (IL-2) is a T-cell-derived lymphokine critical in the activation and proliferation of T cells, B cells, and lymphokine-activated killer cells. It is a glycoprotein of approximately 15,500 daltons that is synthesized and secreted after activation by antigen or mitogen. By using the analogs 8 azidoadenosine 5'-[gamma-32P]triphosphate [( gamma-32P]8N3ATP) and nicotinamide 2 azidoadenine [adenylate-32P]dinucleotide [( alpha-32P]2N3NAD+) as photoaffinity probes, we have detected specific, metal ion-requiring nucleotide binding sites on recombinant human IL-2 (rhIL-2). The specificity of these nucleotide interactions with rhIL-2 was demonstrated by saturation effects and by competition by the parent nucleotides at physiologically relevant concentrations. Saturation of photoinsertion into rhIL-2 occurred at 50 microM [gamma-32P]8N3ATP; a half-maximal decrease of its photoinsertion at 10 microM was obtained with 22 microM ATP. Saturation of photoinsertion with [alpha-32P]2N3NAD+ was observed at 180 microM; a half-maximal decrease of its photoinsertion at 10 microM was effected by 10 microM NAD+ and by 5 microM 3-aminobenzamide. The extent of photoinsertion of both photoprobes into rhIL-2 varied with the presence of different divalent metal ions. rhIL-2 photolabeling with [gamma-32P]8N3ATP appeared to be dependent on the presence of metal ion. It was effectively labeled in the presence of Mg2+ and photoinsertion was increased with the addition of Zn2+ at micromolar concentrations. Also, rhIL-2 underwent slow autophosphorylation by an intramolecular mechanism using [gamma-32P]8N3ATP as well as nonphotoactive nuceotide. The biological significance of these interactions is unknown, but their specificity suggests that nucleotide binding may be involved in the bioactivity of IL-2. PMID- 2105503 TI - Phage shock protein, a stress protein of Escherichia coli. AB - Filamentous phage infection induces the synthesis of large amounts of an Escherichia coli protein, phage shock protein (Psp), the product of a previously undescribed gene. This induction is due to the phage gene IV protein, pIV, an integral membrane protein. The uninduced level of Psp is undetectable, but when induced by prolonged synthesis of pIV, it can become one of the most abundant proteins in the cell. Psp is also synthesized transiently in response to several stresses (heat, ethanol, and osmotic shock). High-level synthesis occurs only after extreme treatment. Unlike the members of the heat shock regulon, Psp induction does not require the heat shock sigma factor, sigma 32; some stimuli that elicit sigma 32-dependent heat shock proteins do not induce Psp synthesis. The level of Psp induction after extreme stress is even higher in sigma 32 mutant cells, which are unable to mount a normal heat shock response, suggesting that these parallel stress responses are interrelated. PMID- 2105504 TI - Interferon gamma regulates binding of two nuclear protein complexes in a macrophage cell line. AB - Interferon gamma (IFN-gamma) is a potent inducer of major histocompatibility complex (MHC) antigens during normal immune responses and in abnormal responses in autoimmune disease. In this report we identify two nuclear factors whose binding to the murine E beta class II MHC beta-chain gene is regulated by this cytokine. IFN-gamma stimulation of murine macrophages results in the appearance of increased binding of one protein complex, complex A, and decreased binding of a second, faster migrating protein complex, complex B. Although the contact residues for both of these proteins lie within the highly conserved Y-box transcriptional element, their binding specificity differs. The protein in complex B is a CCAAT-box-binding protein that may be similar or identical to NF-Y or YB1, previously identified class II Y-box-binding proteins. The DNA sequence requirements for the binding of the slower migrating complex, complex A, are not limited to CCAAT-box sequences but include sequences upstream of the Y box. These upstream sequences are required both for IFN-gamma-induced gene transcription and for IFN-gamma-induced modulation of binding activity. These data suggest a model in which upstream sequences contribute to formation of a lymphokine-regulated complex downstream. The IFN-gamma-induced binding protein described as complex A in this report differs from the IFN-gamma, -alpha, or -beta-induced nuclear factors previously identified. PMID- 2105506 TI - Selenium and immune cell functions. II. Effect on lymphocyte-mediated cytotoxicity. AB - Selenium (Se) is an essential nutritional factor with a chemopreventive potential. This study examined the ability of C57BL/6J mice, maintained for 8 weeks on Se-deficient (0.02 ppm Se), normal (0.20 ppm Se), or Se-supplemented (2.00 ppm Se) Torula yeast-based diets, to generate cytotoxic lymphocytes (CTL) and to destroy tumor cells. CTL were generated in vivo by intraperitoneal immunization with P815 cells and in vitro by allogeneic stimulation of cells from animals maintained on a normal diet in media supplemented with 1 x 10(-9) to 1 x 10(-6) M Se (as selenite). Lymphocytes from animals maintained on the Se supplemented diet had a greater ability to destroy tumor cells than lymphocytes from animals maintained on the normal diet, whereas Se deficiency reduced the cytotoxicity. The effects on cytotoxicity were accompanied by parallel changes in the levels of lymphotoxin produced. The greatest enhancement of tumor cytodestruction occurred with supplementation of 1 x 10(-7) M Se, whereas with 1 x 10(-6) M there was inhibition of the cytotoxic responses. The stimulatory effect of Se occurred during the phase of CTL generation rather than during the lytic phase of cytotoxicity. These results indicated that Se supplementation enhances CTL generation and the ability of a host to destroy malignant cells, whereas Se deficiency has the opposite effect. PMID- 2105505 TI - Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: application to diagnosis and blood screening for posttransfusion hepatitis. AB - A cDNA clone has been derived from the plasma of a chimpanzee with chronic non-A, non-B viral hepatitis (NANBH). We have assayed for antibodies reacting with the encoded antigen in sera from posttransfusion hepatitis patients (643 samples from 23 patients) and their corresponding donors collected during the past 10 years in Japan. The antibody was detected in 15 out of 17 (88.2%) posttransfusion NANBH (PT-NANBH) patients whose sera over time displayed multiple alanine aminotransferase (ALT) peaks. In general, the antibody was detected after several peaks of serum ALT elevations and, once detected, it persisted for years. In contrast to the patients of chronic hepatitis, the antibody was barely detected in patients with a single episode of ALT elevation (1 out of 6). Of the 15 well defined cases of PT-NANBH that showed multiple ALT peaks and hepatitis C virus seroconversions, 11 (73.3%) were shown to be transfused with at least one unit of blood positive for the antibody. The retrospective analysis showed that all tested donor blood found to be positive for the antibody had been transfused to recipients who afterwards developed NANBH. These data strongly suggest that the cloned cDNA originated from an etiological agent of NANBH termed the hepatitis C virus. Furthermore, the present study demonstrates that had the screening been done with the anti-hepatitis C virus assay, 11 out of 17 (64.7%) cases of chronic PT-NANBH and 1 out of 6 (16.6%) acute PT-NANBH would have been prevented. The antibody assay thus can be used for diagnosis and blood screening for PT-NANBH. PMID- 2105507 TI - Gonadotropin and prolactin secretion following intraventricular administration of morphine in gilts. AB - The effects of central nervous system administration of morphine on secretion of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were investigated in ovariectomized gilts stereotaxically implanted with lateral ventricular cannulas. In Experiment 1, mean serum LH and follicle-stimulating hormone concentrations and serum LH pulse frequency were unaffected by artificial cerebrospinal fluid administration (P greater than 0.1), but decreased (P less than 0.01) in 8 of 11 gilts when 500 micrograms of morphine were given 3 hr later. Serum LH pulse amplitude was unaffected (P greater than 0.1) by cerebrospinal fluid or morphine injection. In Experiment 2, luteinizing hormone concentrations decreased (P less than 0.0001) and prolactin concentrations increased (P less than 0.0001), but follicle-stimulating hormone concentrations did not change (P greater than 0.1) after 500 micrograms of morphine. Gonadotropin responses to 10 micrograms of gonadotropin-releasing hormone, given 2 hr after intraventricular injection, were similar (P greater than 0.1) for morphine- and cerebrospinal fluid-treated gilts. These results indicate that morphine inhibits LH secretion at the level of the central nervous system, and are consistent with the concept that endogenous opioid peptides participate in the regulation of gonadotropin and prolactin release in pigs. PMID- 2105508 TI - The effect of alcohol on HIV infection in vitro. PMID- 2105509 TI - Interferon-gamma: producer cells, activation stimuli, and molecular genetic regulation. PMID- 2105510 TI - Flumazenil: potential implications for hepatic encephalopathy. PMID- 2105511 TI - Improving psychiatric consultation to nonpsychiatrist physicians. AB - Nonpsychiatrist physicians were surveyed regarding problems that they had experienced when seeking a psychiatric consultation or treatment referral. They gave three main reasons for not referring more patients to psychiatrists: a belief that other mental health professionals could do as well at less cost, that psychiatrists were less available to discuss patients, and that greater stigma was attached to seeing a psychiatrist than seeing other mental health professionals. Psychiatrists might improve their consultation and referral networks by addressing the misperceptions of their nonpsychiatrist physician colleagues. PMID- 2105512 TI - Secondary sagittal posterior anorectoplasty. AB - From October 1984 to December 1986, 25 continence-improving operations were performed at the Paediatric Surgical Clinic of the Children's Hospital, Cologne. Smooth muscle inversion plasties were carried out during abdominosacroperineal pull-through procedures in eight neonates. Anterior sagittal anorectoplasties were employed in four female neonates. Secondary continence-improving procedures had to be carried out in 13 patients, with secondary sagittal anterior rectoplasties in 5 instances and posterior sagittal anorectoplasties in another 7 instances. Gracilis transposition according to Pickrell was employed in one boy. Among the seven children who underwent posterior sagittal rectoplasty, there were four patients where remnants of earlier gracilis or gluteus maximus plasties could be additionally used for creation of a continent sphincter apparatus. Among the 13 older patients with secondary continence-improving operations, 7 achieved complete continence and 6 markedly improved continence effecting continence for solid and pultaceous stools, but soiling under stress and diarrhoea. No child remained entirely incontinent. PMID- 2105513 TI - Total correction of complete atrioventricular canal: surgical technique and analysis of long-term results. AB - Surgery for total correction of complete AVC can be done with low early and late mortality. The operative risk is high only in patients who reach the operating room in a near moribund condition (NYHA V). There is clinical evidence that early operation - before the onset of pulmonary vascular disease - will further lower early and late mortality. The surgical technique has been refined to avoid late reoperation for left atrioventricular valve incompetence. The early and late results of operative therapy compare favourably with the natural history of this complex congenital cardiac disease. PMID- 2105514 TI - Nonosseous lesions of the anterior cruciate ligaments in childhood and adolescence. AB - Damage of the knee joint has increased during the last few years owing to overindulgence in sports. The anterior cruciate ligaments play a major role in knee joint stability. Treatment of injured knee joint structures in childhood and adolescence is more complicated than in adults. From 1972 to 1987 we have seen 330 patients with knee injuries, 28 of whom had nonosseous lesions of the anterior curciate ligaments. Of these, 20 were followed-up; 17 children were operated on primarily, 3 were conservatively immobilized. On follow-up, 15 patients showed signs of residual instability. Primary treatment depends on the presence and the extent of associated injuries of the knee joint. PMID- 2105515 TI - Treatment of achalasia by the endoscopic-pneumatic dilatation method. AB - There is no definite cure for the loss of oesophageal peristalsis and incomplete relaxation of the lower oesophageal sphincter associated with achalasia. Pneumatic dilatation is a simple and safe method of achieving symptomatic improvement of the oesophageal passage. By this means five young patients became free of complaints within an average observation period of 6 3/4 years. PMID- 2105516 TI - Haemostasis in injuries of parenchymatous organs by infrared contact coagulation. AB - A series of 11 children aged from 1 day to 12 years is reported in which infrared contact coagulation with a sapphire coagulator was used for haemostasis in liver and splenic injuries. Seven children were cured. The four deaths were not related to the injuries of parenchymatous organs. Infrared contact coagulation is a suitable and cheap method for organ preservation in injuries or other pathological conditions of parenchymatous organs in childhood. PMID- 2105517 TI - The Shaw haemostatic scalpel in paediatric surgery: clinical report on 3000 operations. AB - This report presents the experience in a prospective series of 100 operative procedures in all fields of paediatric surgery with the Shaw haemostatic scalpel, which we have subsequently used in more than 3000 further operations. The Shaw scalpel proved to be advantageous in about 80% of major cases. The scalpel cuts tissue with a sharp steel edge, like a cold scalpel, and simultaneously seals blood vessels by heat thermally conducted to the tissue from heated blade which is electrically insulated from the patient. The heat seals most small blood vessels (under 2 mm) as they are cut. Since no electric current passes through the patient, a grounding pad is not needed and the risk of accidental electrical current burns at grounding sites is eliminated. Muscle stimulation associated with the use of a normal cautery is avoided, improving surgical precision of cutting. The Shaw haemostatic scalpel minimizes damage to the tissue as compared with other thermocoagulating instruments. Since it seals small vessels as it cuts tissue, it largely eliminates the flow of blood into the incised area and allows better visibility of the surgical field. The use of the scalpel requires a different cutting technique which is however easy to learn. The Shaw haemostatic scalpel reduces blood loss and overall operating time in major cases. It is relatively inexpensive and can be recommended for use in paediatric surgery. PMID- 2105518 TI - Liver resection with the Sonocut ultrasonic knife. AB - Previous reports and our findings suggest that resection by ultrasound is of appreciable merit in liver surgery. Blood can be saved and bile leakage diminished as the larger vessels and bile ducts can be skeletonized unharmed, whereas the dissector selectively carries away the parenchyma. Otherwise virtually inaccessible tumours can be approached. The ultrasonic dissector/aspirator does not harm the tissue in depth beyond the resection surface and thus not much devitalized tissue is left in the wound. PMID- 2105519 TI - Lasers in pediatric surgery. AB - During the last few years the laser has become a very interesting instrument in pediatric surgery. This is the result of the wide variation in tissue interactions and the possibility of specific applications. The CO2 laser is a highly precise cutting instrument whereas the argon laser has its great advantage in the treatment of superficial vascular anomalies. The most important laser in pediatric surgery is the Nd:YAG laser, on the one hand because its radiation can be transmitted by fibres, on the other because with the relationship between interaction time and power density, and the choice of application, it is possible to change the tissue interaction from precise cutting to specific coagulation and homogeneous coagulation. As a result, indications for lasers in pediatric surgery range from the treatment of superficial haemangiomas to typical endoscopic procedures and the resection of parenchymatous organs and tumours. PMID- 2105520 TI - Electroresection with a new endotracheally applicable resectoscope. AB - Besides dilatation, cryotherapy, laser and surgical resection, the technique of endoscopic, endotracheal electroresection provides an alternative in the treatment of endotracheal stenoses. The instrument is similar to the resectoscope used in urology, but additionally equipped with a longer action range and respiration facility. It is insulated at the tip of the shaft. The electroresectoscope was employed on 64 occasions at our institution in three indications: endotracheal diseases, granulomas following tracheostomy; and short subglottic membrane stenoses, partly secondary to long-term intubation. Indications, advantages and drawbacks of the method are discussed. PMID- 2105521 TI - Experimental studies on caustic burns of the stomach by aggressive chemicals. AB - The treatment of caustic burns of the stomach in childhood by acids, alkalis and especially soldering fluids has remained without any clear concept so far. Surgical treatment consists of therapy of acute complications or late sequelae. Early endoscopy enables one to decide between conservative treatment and early laparotomy. Animal experiments were performed in albino rats for the development of a therapeutic concept. Because of its amphoteric and aggressive nature, soldering fluid zinc dissolved in 33-50 M saline) was used as the caustic substance. Clear demarcation and tissue changes can be recognized after 6-8 h, at the earliest. Laparotomy aiming at protective plication or atypical gastric resection should be performed at that time, if endoscopy reveals a third-degree caustic burn of the stomach. PMID- 2105522 TI - Intraperitoneal application of fibrinogen gluing in the rat for adhesions prophylaxis. AB - The suitability of fibrinogen gluing for prophylaxis of intraperitoneal adhesions was investigated experimentally. Small bowel slings, traumatized previously, were covered by a layer of fibrinogen 2-3 mm thick to see whether formation of adhesions could be prevented. In the experiments 50 rats of both sexes were observed over 21 days. Following mechanical traumatization of the terminal ileum the visceral peritoneum was coated with fibrinogen, whereas animals of the control group did not receive fibrinogen coating. Macroscopic and microscopic findings after 1, 3, 7, 14 and 21 days yielded the following results: 1. Fibrinogen dissolution and resorption occurred for 3-14 days following operation. 2. On autopsy, all animals of the control group showed massive, extended adhesions; two of the controls died on the 6th postoperative day from peritonitis. 3. None of the treated animals exhibited extended adhesions. 4. Histological examinations revealed regeneration of the injured serosa and healing of the bowel wall below the fibrinogen coating. 5. Fibrinogen applied to intact peritoneal serosa (without injury) is entirely resorbed without formation of adhesions. PMID- 2105523 TI - Surgical techniques in short bowel syndrome. AB - An operation according to Bianchi in a 2-year-old girl is described and indications as well as technical procedure are discussed. The girl was born with a gastroschisis. There was a jejunal perforation 10 cm below the ligament of Treitz caused by a volvulus. Only 20 cm of the jejunum remained. Moreover, only the left part of the colon was present. Total parenteral nutrition for 2 years was necessary. The principle of the operation is based on a longitudinal division of the remaining bowel and a creation of two separate bowel tubes out of the divided bowel halves, thus effecting an isoperistaltic serial connection by means of two anastomoses. This is technically possible since each half of the bowel wall has its own blood supply. The vessels originating from the mesenterium branch off before they reach the bowel wall so that the mesenteric dissection line can be anastomosed longitudinally with the antimesenteric border. This results in doubling of the bowel length, narrowing of the preoperatively dilated bowel diameter, closer contact of bowel contents with the mucosa, prolonged transit time and a Bacteroides colonization which is reduced by more effective peristalsis. Indications, time of operation and our own experiences are discussed and three cases are described. All children are alive and show marked improvement in nutrition. PMID- 2105524 TI - Small bowel transplantation: report of a clinical case. AB - Extensive small bowel resection may become necessary for several reasons in children and adults. The only causal therapy of short bowel syndrome is small bowel transplantation. So far severe immunological problems have caused deleterious results despite technically successful transplantation. A clinical case of small bowel transplantation in a child is reported. The 3-year-old boy had been operated on for volvulus which had led to nearly total gangrene of the whole small bowel. Finally, only 4 cm of jejunum could be saved. Total parenteral nutrition (TPN) therefore became necessary. Small bowel transplantation was carried out with the mother as donor; transplantation technique is described in detail. Postoperative immunosuppression was performed by administration of cyclosporin A and prednisolone. Because of graft rejection, the graft had to be removed on the 12th postoperative day. At present, the child is well and on TPN again. This case shows that small bowel transplantation by living related organ donation is technically possible without impairment of the donor's quality of life. Further experimental and clinical work should be encouraged. PMID- 2105525 TI - Deep anterior resection with circular stapled anastomosis of congenital megacolon: clinical results. AB - This report deals with instrumental suture in the deep anterior rectum resection when treating Hirschsprung's disease. The concept includes: ensuring diagnosis, cleaning the intestines, antibiotic prophylaxis, intraoperative testing of the anastomosis and postoperative X-ray by a standardized technique. Our first experience in the use of the stapler was gained with ten patients. One case of anastomosis insufficiency occurred. With the stapler apparatus, safe anastomosis was possible. The stapler facilitates anastomoses in deep resections. Therefore, a deep resection of the pathological segment in Hirschsprung's disease is possible. The practicality of the stapler and the favourable clinical experience justify the continued application of the instrumental suture technique in children's surgery. PMID- 2105526 TI - Augmentation by cytochalasin B of antigen receptor-mediated activation of normal and malignant human B lymphocytes. PMID- 2105527 TI - Characterization of murine liver-derived inhibitory protein. AB - Murine liver-derived inhibitory protein (LIP) capable of inhibiting human lymphocyte proliferation was highly purified from liver extract. Its molecular weight determined by gel filtration and SDS-PAGE was 105,000 and 38,400 respectively. LIP moved electrophoretically at the gamma-globulin region. Its activity in inhibiting lymphocyte proliferation was temperature-stable up to 60 degrees C, and pH-stable between 4 and 11. It was not cytotoxic to lymphocytes as shown in 51Cr-release experiments. The purified LIP possessed arginase activity. PMID- 2105528 TI - Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. AB - Activity of the immunoglobulin heavy and kappa light chain gene enhancers depends on a complex interplay of ubiquitous and developmentally regulated proteins. Two complementary DNAs were isolated that encode proteins, denoted ITF-1 and ITF-2, that are expressed in a variety of cell types and bind the microE5/kappa 2 motif found in both heavy and kappa light chain enhancers. The complementary DNAs are the products of distinct genes, yet both ITF-1 and ITF-2 are structurally and functionally similar. The two proteins interact with one another through their putative helix-loop-helix motifs and each possesses a distinct domain that dictates transcription activation. PMID- 2105529 TI - Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. AB - Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-[18F]fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant. PMID- 2105530 TI - "Subjective perception". PMID- 2105531 TI - Perforated jejunal diverticulum with multiple hepatic abscesses. AB - We have described a patient with multiple hepatic abscesses caused by a perforated jejunal diverticulum with a presumed route of infection via the portal vein. Patients with hepatic abscesses and no known source of infection should be evaluated for a contained mesenteric perforation of the gastrointestinal tract. Finally, in patients who fail to respond promptly to percutaneous catheter drainage of a liver abscess, a continuing source of infection, such as perforation of a jejunal diverticulum, should be suspected. PMID- 2105532 TI - Medical surveillance of hazardous waste site workers exposed to polychlorinated biphenyls (PCBs). AB - A potential for occupational exposure to PCBs exists within the electrical utility industry, especially where PCB-containing equipment has been serviced. PCBs can also be found at hazardous waste sites, in sewage sludge, and in soot from transformer fires. The health effects, biological monitoring, and medical surveillance of PCBs are all discussed in this review. PMID- 2105533 TI - Management of anteriorly located C1-C2 neurofibromata. AB - The authors discuss their recent experience with anteriorly located C1-C2 neurofibromata in five patients with cervical myelopathy and magnetic resonance scans consistent with intradural extramedullary masses in this region. Surgery was performed using a posterolateral approach with microscopic intradural exploration. Gross total intradural tumor removal was achieved in all cases. Improvement in cervical myelopathy occurred in all patients. This report concludes that C1-C2 neurofibromata located anterior to the spinal cord can be totally and safely removed using a posterolateral approach. Improvement in neurologic dysfunction accompanies posterior decompression and gross total intradural tumor removal. PMID- 2105534 TI - Treatment planning and delivery in neutron radiotherapy of soft tissue sarcomas. AB - Well differentiated soft tissue sarcomas may benefit from fast neutron radiotherapy, in particular inoperable and recurrent tumors and tumors with residual disease after non-radical surgery. Treatment planning in a multidisciplinary pretherapeutic approach has to be based on tumor size and site and histopathology. Target volume definitions for potential microscopic spread and for the high risk region of local recurrence have to consider the preoperative tumor localization (imaging), the biological behavior and the extent of surgery. GI/II, T1-3 tumors after intralesional or marginal resection are indications for neutron therapy. Treatment planning and delivery has to take into account the narrow therapeutic range of fast neutrons and include individual immobilization devices, manufacturing of bolus and CT based computed dose calculations. Neutron radiotherapy techniques at the d, T generator are comparable to photon techniques except individual beam shaping, field size and portal verification. Total dose is 16 Gy neutrons in the high risk region and 12 to 13 Gy in the region of potential microscopic spread. PMID- 2105535 TI - Xenografts of five human leiomyosarcomas: radiation response after 60cobalt- and d(14)+Be neutron single doses. AB - Five permanently established xenograft lines of human soft tissue sarcomas were irradiated with single doses of 5.8 MeV d(14)+Be neutrons and of 60Co rays, respectively, at several dose levels to generate dose response relationships. The tumors were clamped ten minutes prior to and during irradiation to induce uniform hypoxia. All tumours were previously characterized by means of histomorphology, tumour doubling times (DT's), DNA-index and enzyme pattern of the lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (GPD). According to these criteria, three out of five leiomyosarcomas were identical referring to the biopsy of origin, whereas two had changed in successive passages. For the different tumour lines, specific growth delays ranged from 0 to 8.7 after 5.3 Gy neutrons and from 0 to 11.4 after 16 Gy60Co, respectively. In terms of radiosensitivity for different single doses and irradiation qualities, a highly significant overall correlation (rs = 0.82 +/- 0.06) was found for the ranking of the tumours with respect to the growth delay and specific growth delay endpoints. No correlation was found between tumour doubling times and the relative biological effectiveness (RBE). In general, calculated RBE-values decreased with increasing effect level. For the five tumour lines, RBE-values ranged from 1.6 to 12.7 and 2.0 to 4.4 at specific growth delays of 0.5 and 2.0, respectively, under acutely hypoxic conditions. These results indicate a potential advantage for neutrons in a subgroup of human soft tissue sarcomas compared with sparsely ionising irradiation. PMID- 2105536 TI - Good news for a tenth anniversary. PMID- 2105537 TI - Neutron boost irradiation of soft tissue and chondrosarcomas at the West German Tumour Centre in Essen. AB - In this retrospective study, the results of postoperative neutron boost therapy for 40 soft tissue- and 18 chondrosarcomas are presented. In 65.5% and 34.5% of all cases, microscopic to macroscopic tumour residual was left postoperatively. Locally advanced and moderate to highly malignant tumours were found at surgery in 81% and 69%, respectively. Except for seven patients with a whole series of neutrons to 16 Gy, the other cases were treated with initially 40 to 50 Gy photons and a subsequent neutron boost of 4 to 6 Gy. The median follow-up was 29.3 and 36.2 months for the soft tissue- and chondrosarcomas. The actuarial three-year local control and overall survival rates were 69.3% and 91% for soft tissue- vs. 55.6% and 62.9% for chondrosarcomas. With regard to the extension of surgery (microscopic or macroscopic residual), local control rates of 80% and 60% for soft tissue- vs. 62.5% and 40% for chondrosarcomas were observed. The overall local failure rate was 32.8% with a median disease-free interval of ten respectively eleven months for soft tissue and chondrosarcomas. 17 out of 19 local recurrences were due to inadequate irradiation portals for the neutron boost or to insufficient total doses in the initially treated photon target volume. PMID- 2105538 TI - Functions and tocopherol content of blood platelets from elderly people after low intake of purified eicosapentaenoic acid. AB - Elderly people present an increased incidence of atherosclerosis and vascular cerebral damages, associated with blood platelet hyperactivity and a stimulation of arachidonic acid metabolism in vivo. The effects of a low intake of purified eicosapentaenoic acid (EPA) on platelet hyperactivity in old human subjects has been investigated. In a randomized, double blind study, 8 people took during 2 months a daily intake of 100 mg of eicosapentaenoic acid (EPA) given as a triglyceride (1,3-dioctanoyl,2-eicosapentaenoyl-glycerol), and 8 other subjects ingested a placebo. A slight, but significant reduction of platelet-rich plasma aggregation in response to epinephrine and arachidonic acid occurred after EPA intake, as well as a decreased aggregation of washed platelets induced by thrombin, although collagen- and U-46619-induced aggregations were not significantly modified. EPA intake failed to affect arachidonic acid metabolism in thrombin-stimulated platelets or in clotted venous blood. The urinary excretion of thromboxane, 6-keto-PGF1 alpha and their 2,3-dinor-metabolites was also not modified. Similarly, no change in the plasma and platelet lipid fatty acid compositions could be observed. Platelet, but not plasma, alpha- and gamma tocopherol were enhanced by EPA intake. An increase of platelet vitamin E has been associated with a decrease of aggregation, especially in vitamin E-deficient subjects, like elderly people. Therefore, low intake of EPA might have contributed to inhibit platelet aggregation by increasing cellular vitamin E. PMID- 2105539 TI - Fluctuations of euglobulin lysis time, tissue plasminogen activator, and free and total plasminogen activator inhibitor levels in plasma in daytime. AB - Blood was taken from healthy 15 males and 10 females at 9:30 h, 10:00 h and 12:30 h. The euglobulin fraction was prepared and clotted by the addition of human thrombin. The clot lysis time shortened significantly from 9:30 h to 10:00 h (p less than 0.01) and further to 12:30 h (p less than 0.01). Plasma levels of tissue plasminogen activator (t-PA) antigens did not change from 9:30 h to 10:00 h, but slightly and significantly to 12:30 h (p less than 0.01). Plasma levels of free plasminogen activator inhibitor-1 (PAI-1) and complex of t-PA-PAI-1 decreased from 9:30 h to 10:00 h (p less than 0.02) and to 12:30 h (p less than 0.01). Plasma levels of total PAI-1 (free plus complex) decreased from 9:30 h to 10:00 h (p less than 0.01) and to 12:30 h (p less than 0.01). These results suggest that a major factor contributing to the enhanced fibrinolytic activity of the euglobulin fraction may be a level of PAI-1 (free and total). PMID- 2105540 TI - Effect of exercise, DDAVP, and epinephrine on the factor VIII:C/von Willebrand factor complex in normal dogs and von Willebrand factor deficient Doberman pinscher dogs. AB - Endothelial cells in biopsied blood vessels from von Willebrand factor (vWf) deficient Doberman pinscher dogs contain immunologically detectable vWf. These dogs and normal dogs were treated with DDAVP (0.6 microgram/kg) and epinephrine (0.5 microgram/kg/min for 30 minutes) and were exercised, using 5 different exercise protocols, (3-4 m/s for 5-40 minutes at 0-5% grade) to determine if treatments reported to increase plasma factor VIII:C/vWf complex in humans would elevate canine plasma vWf. Following the two most strenuous exercise conditions- 30 and 40 minutes--plasma von Willebrand factor antigen (vWf:Ag) increased in normal dogs by 30% and 70%, respectively. Factor VIII:C was increased 47% by the most strenuous exercise conditions. The vWf-deficient dogs would not exercise beyond 30 minutes and neither vWf:Ag nor factor VIII:C activity increased. Following DDAVP, plasma vWf:Ag increased in the normal dogs by 47% and factor VIII:C activity was increased by 48%. Factor VIII:C activity increased by 30% in the vWf-deficient dogs, but there was only a slight change in vWf:Ag. Bleeding time decreased in 5 of 6 vWf-deficient dogs. In the normal dogs vWf:Ag increased by 14% after epinephrine infusion, but factor VIII:C activity did not change; neither parameter was altered in the vWf-deficient dogs. While the factor VIII:C/vWf:Ag complex was increased in the normal dog by exercise and DDAVP, the increase is not as pronounced as has been reported for humans. It is not known whether the poor response of the vWf-deficient dog is due to low levels of vWf in their endothelium or to a release defect. PMID- 2105541 TI - Effect of ICRF-187 pretreatment against doxorubicin-induced delayed cardiotoxicity in the rat. AB - Doxorubicin (DXR), administered iv in rats at the weekly dose of 3 mg/kg for 5 weeks, significantly impaired body weight gain and induced irreversible ECG alterations, mainly consisting of a progressive prolongation of ST and QT intervals. Five weeks after the last DXR administration, the contractile performance of atria isolated from treated animals was significantly reduced. At the same time, relevant morphologic lesions, consisting of myocyte vacuolization and myofibrillar loss, were also present in the myocardium of the same rats. The study showed that ICRF-187, administered ip at a dose of 125 mg/kg, significantly prevented body weight loss. QT and ST prolongation, and the decreased contractile force induced by DXR. In addition, ICRF-187 caused a significant reduction in incidence and severity of myocardial lesions. The cardioprotective effect of ICRF 187 is not mediated by a modification in DXR pharmacokinetics in heart, since the drug was actually found to increase DXR uptake in myocardial cells. PMID- 2105543 TI - Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. AB - We studied whether hemostatic abnormalities contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation. Hemostatic function was studied in four age-matched groups: 20 patients with nonvalvular atrial fibrillation and a previous ischemic stroke, 20 patients with nonvalvular atrial fibrillation without a previous stroke, 20 stroke patients with sinus rhythm, and 40 healthy controls. Both groups with nonvalvular atrial fibrillation had significantly higher concentrations of von Willebrand factor, factor VIII:C, fibrinogen, D-dimer (a fibrinolytic product), beta-thromboglobulin, and platelet factor 4; a significantly higher fibrinogen/antithrombin ratio; and significantly higher spontaneous amidolytic activity than the healthy controls. Prekallikrein levels were significantly lower in both groups with nonvalvular atrial fibrillation. Stroke patients with sinus rhythm had normal hemostatic function, normal concentrations of platelet-related factors, and a slightly increased concentration of fibrinopeptide A compared with the healthy controls. Both groups with nonvalvular atrial fibrillation differed from the stroke patients with sinus rhythm as they did from the healthy controls. No difference in hemostatic function was seen between the nonvalvular atrial fibrillation patients with and without a previous ischemic stroke. Thus, alterations in hemostatic function may contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation. PMID- 2105542 TI - Cellular lead toxicity and metabolism in primary and clonal osteoblastic bone cells. AB - A knowledge of bone lead metabolism is critical for understanding the toxicological importance of bone lead, as a toxicant both to bone cells and to soft tissues of the body, as lead is mobilized from large reservoirs in hard tissues. To further understand the processes that mediate metabolism of lead in bone, it is necessary to determine lead metabolism at the cellular level. Experiments were conducted to determine the intracellular steady-state 210Pb kinetics in cultures of primary and clonal osteoblastic bone cells. Osteoblastic bone cells obtained by sequential collagenase digestion of mouse calvaria or rat osteosarcoma (ROS 17/2.8) cells were labeled with 210Pb as 5 microM lead acetate for 20 hr, and kinetic parameters were determined by measuring the efflux of 210Pb from the cells over a 210-min period. The intracellular metabolism of 210Pb was characterized by three kinetic pools of 210Pb in both cell types. Although the values of these parameters differed between the primary osteoblastic cells and ROS cells, the profile of 210Pb was remarkably similar in both cell types. Both types exhibited one large, slowly exchanging pool (S3), indicative of mitochondrial lead. These data show that primary osteoblastic bone cells and ROS cells exhibit similar steady-state lead kinetics, and intracellular lead distribution. These data also establish a working model of lead kinetics in osteoblastic bone cells and now permit an integrated view of lead kinetics in bone. PMID- 2105544 TI - Premature stroke in a family with lupus anticoagulant and antiphospholipid antibodies. AB - Lupus anticoagulant and antiphospholipid antibodies are associated with thromboembolic phenomena in individuals both with and without systemic lupus erythematosus. A 32-year-old woman (the index case) with lupus anticoagulant, multiple cerebrovascular events, and a family history of premature stroke raised the possibility of a familial diathesis. Histories or interviews, examinations, and blood tests were obtained for 23 members of four generations of her family. Four individuals had suffered strokes and three more had suffered neurologic symptoms. Two living individuals who had suffered strokes, two individuals with neurologic symptoms, and five asymptomatic individuals had antiphospholipid activity in their blood. In addition, a cousin of the index case was found to have systemic lupus erythematosus and antiphospholipid activity. Elevated concentrations of von Willebrand factor antigen were found associated with some positive lupus anticoagulant assays, the highest concentrations in the two individuals with stroke. The characteristic presentation of the index case and her good response to treatment suggests that further studies of families in whom antiphospholipid antibodies may represent a risk factor for stroke is worthwhile. PMID- 2105545 TI - Successful allogeneic transplantation of rat islets expressing cytokine-induced major histocompatibility complex class II antigen. AB - Cultured neonatal rat (F344, RT1(1v1)) islets that were devoid of MHC class II (OX6) antigen and antigen-presenting cells were treated with recombinant murine interferon (IFN-gamma) and/or recombinant murine tumor necrosis factor (TNF alpha) in vitro. The IFN-gamma and TNF-alpha resulted in some disruption of the integrity of the islets by 7 days of culture, but the combination resulted in disaggregation of the islets within 7-8 days. Insulin release into the medium and secretion in response to glucose were adversely affected by the cytokines. The IFN-gamma resulted in expression of class II antigen on about 10% of the endocrine cells after 3-4 days in culture. This effect of IFN-gamma was potentiated by TNF-alpha resulting in 27% of the cells expressing class II antigen. Islets treated with IFN-gamma and TNF-alpha alone or in combination were not rejected in a subsequent transplant underneath the kidney capsule of WF rats (RT1u). We conclude that expression of class II antigen alone is not sufficient to initiate an allogeneic rejection response, but that cytokine-mediated destruction of endocrine cells could be the basis of immune-mediated islet-cell loss in islet-allograft rejection or autoimmune diabetes. PMID- 2105546 TI - Increased major histocompatibility complex antigen expression in unilateral ischemic acute tubular necrosis in the mouse. AB - In many studies of renal transplant recipients, acute tubular necrosis has been shown to predispose to a higher rate of graft loss, apparently due to rejection, but the mechanism of this effect is unknown. One possibility is an increased immunogenicity of the graft. To study this possibility, we examined the expression of major histocompatibility complex antigens in kidneys damaged by ischemia, using a mouse model of ischemic ATN. ATN was produced in the left kidney of male CBA mice by temporary clamping of the vascular pedicle for up to 60 min. Class I and II MHC expression was quantified by the extent of binding of monoclonals in radioimmunoassay, after 1 to 35 days in both kidneys. MHC induction was localized by indirect immunoperoxidase staining. Specific steady state mRNA for beta 2 microglobulin and class II were quantified by northern blotting using 32P-labeled probes. Changes in MHC expression were assessed by comparing the ischemically injured left kidney to the control right kidney. By day 1, ATN was evident by histology but there was no change in MHC expression. By day 3, class I was increased in the left kidney by 3-6-fold over the right. In tissue sections, the class I increase was localized to tubular epithelial cells. Starting on day 7 and persisting to day 35, class II was increased by 1.5 to 3 times for the ischemic kidney over the control, primarily in interstitial cells but also in tubular cells. This increase in class II was associated with the appearance of Thy 1.2-positive cells in the interstitial areas. Increased antigen expression was preceded by increased steady state mRNA. Thus unilateral ischemic ATN causes increased MHC expression in tubular cells and the accumulation of an inflammatory infiltrate, both of which may contribute to the increased rate of rejection and graft loss in ischemically injured kidneys. PMID- 2105547 TI - Factors influencing islet transplantation. Number, location, and metabolic control. PMID- 2105548 TI - Lovastatin treatment of hypercholesterolemia in renal transplant recipients. AB - The treatment of hypercholesterolemia in renal transplant recipients has been problematic. In the present double-blind study, 11 patients were treated with diet for at least 4 weeks. They were then randomized to placebo or the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, lovastatin (20 mg/day) for 6 weeks, followed by crossover to an additional 6 weeks of lovastatin or placebo. All patients had stable allograft function 8.4 +/- 1.2 years (mean +/- SEM) after transplantation, and received low-dose prednisone and azathioprine immunosuppression. Compared with diet alone, lovastatin caused a 21% reduction in total cholesterol from 307 +/- 14 mg/dL to 244 +/- 13 mg/dL (P less than 0.05). Lovastatin reduced LDL cholesterol 28% from 214 +/- 12 mg/dL to 155 +/- 11 mg/dL (P less than 0.05). Trends toward favorable changes in HDL cholesterol, serum triglycerides, and apolipoproteins were not statistically significant. Liver enzymes, creatine phosphokinase, and renal function remained stable. With lovastatin there was a 27% increase in the WBC (from 6220 +/- 530 cells/mm3 to 7780 +/- 510 cells/mm3, P less than 0.05) that was attributable to a 45% increase in neutrophils (P less than 0.05). This effect of lovastatin, possibly the result of reduced azathioprine bone marrow suppression, could have important implications for immunosuppressive therapy in this patient population. Altogether, these results suggest that lovastatin may be a safe and effective treatment for hypercholesterolemia in renal transplant recipients receiving conventional immunosuppression. PMID- 2105549 TI - [What is cost effectiveness analysis?]. AB - Cost-effectiveness analysis (CEA) is an established economical form of analysis which, in public services, replaces the marketing mechanism. The questions which CEA attempts to answer are: Which form of medical technology is most economically effective where a given disease is concerned. Where and how must the medical technology be commenced. Which group of patients can benefit from a given form of medical technology? It is a prerequisite for employment of CEA that there is unanimity in advance about the object of an activity, eg. a given treatment or procedure in the diagnostic investigation. Several strategies may be employed to ensure that the aim is sufficiently wide: the limits may be explicit; goals may be established which compare years of life with quality of life, or several goals may be present in the goal. The predominant economical expression in CEA is alternative costs which must be sacrificed in order to carry out a certain activity. In order to estimate what is obtained by carrying out an activity, an expression of effect is essential. These are most frequently both of quantitative and also of qualitative character and may be subdivided into three categories: Alterations in the employment of resources. Alterations in production by society. Alterations in the conditions of health of the individual. Doctors are important decisions-makers and distributors of resources in the health services. The questions which a CEA can provide graduated answers to, are the questions that the doctor works with in clinical practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105550 TI - [A review of the types of economic analyses of the health economy]. AB - Great confusion is involved concerning health economics analyses. For example: What is the difference between cost-benefit and cost-effectiveness analyses? Is there a difference between the so-called cost-of-illness analyses? What is a financial analysis? These questions are discussed on the basis of the underlying economic theory and the use of the analyses. In order to avoid terminological confusion, the English terminology is retained. Cost-benefit and cost effectiveness analyses are social economical analyses because they are all embracing as regards what is understood by costs and profits based on the so called welfare economy where cost-benefit analyses are concerned. The theoretical basis for cost-effectiveness analysis is slightly more obscure. Where both forms of analysis are concerned, no concern is shown for who obtains the profits or who pays the costs, i.e. a cross-sectional perspective. The financial analysis contrasts with this because attention is focussed directly on expenditures and revenues and the accounts responsible for the expenses and which obtain the revenues. The cost-of-illness analysis is a confusing but frequently employed and quoted form of analysis where an attempt is made to calculate the costs of a certain disease or injurious agent (alcohol, tobacco, accidents) for the various parties involved. These are subdivided into direct costs, roughly corresponding to the costs of treatment and indirect costs which include e.g. loss of income resulting from the illness, disability or death. This form of analysis is strongly warned against as the results of analysis may easily be misused frequently with absurd implications. PMID- 2105551 TI - [Gelatinous bone marrow transformation]. AB - A case of gelatinous degeneration of the bone-marrow in a man aged 29 years is presented. The condition had developed on account of a combination of prolonged inadequate calorie and protein intake and physically demanding sport (triathlon). This has not been described previously. Accumulation of a gelatinous substance in the bone-marrow was found. Histochemical investigation demonstrated that this consisted of acid-mucopolysaccharides. PMID- 2105552 TI - Enteral nutrition by tube. AB - When oral intake is unsatisfactory or contraindicated, maintenance of nutrition by tube feeding is an alternative to the parenteral route. A large volume of research data supports the decision to use the enteral route whenever possible. Entry of food into the alimentary tract is a stimulus to structural and functional maintenance of that tract. Enteral nutrition can be given via indwelling nasoesophageal, pharyngostomy, esophagostomy, percutaneous or surgical gastrostomy, or enterostomy tube. Use of an appropriate catheter, familiarity with the technique used, and careful patient selection and monitoring are important factors in successful tube feeding. Blenderized pet food diets should be fed whenever possible; commercially available liquid diets provide an alternative when tube caliber or patient factors preclude the use of blenderized foods. PMID- 2105553 TI - Evaluation of acid-base disturbances in calf diarrhoea. AB - The severity of acid-base disturbances in diarrhoeic calves was investigated and a simple, inexpensive method of monitoring them was evaluated. The Harleco apparatus measures the 'total carbon dioxide' in a blood sample, mostly generated from the bicarbonate present, and any abnormalities are mainly due to metabolic acidosis or alkalosis. Its performance was tested against a standard blood gas analyser by comparing the results obtained by both methods with nearly 2000 blood samples from healthy or diarrhoeic calves. After technical modifications, the technique gave excellent precision and accuracy for the clinical evaluation of acid-base balance, using venous whole blood. The samples were very stable, especially at 0 degrees C, but also at room temperature. The normal range (mean +/- 1.96 sd) for total carbon dioxide in whole blood from calves was 21 to 28 mmol/litre. For samples corresponding to mild, moderate or severe acidosis, 79 per cent were correctly classified by the Harleco apparatus and only 0.1 per cent were beyond the adjacent degree of severity. After four days of diarrhoea, the calves which later died had twice the deficit in plasma bicarbonate of those which survived. As death approached, the deficit was almost three times that in surviving calves and the blood pH shortly before death was as low as 6.79 +/- 0.08. The Harleco apparatus was less successful with alkalotic samples, but metabolic alkalosis is less common and usually less severe. PMID- 2105554 TI - Scrapie agent in muscle. PMID- 2105555 TI - Effects of acute hyperventilation on serum potassium in the dog. AB - The effects of increasing respiratory rates on arterial pH, PaCO2, HCO3, and potassium (K) were measured in normal anesthetized dogs. Hyperventilation resulted in increased pH, decreased PaCO2, decreased HCO3, and decreased K compared with those parameters in spontaneously breathing dogs. The changes were related quantitatively: each 10 mmHg decrease in PaCO2 was associated with a pH increase of 0.1, a HCO3 decrease of 2.0 mEq/L, and a K decrease of 0.4 mEq/L. There were no cardiac arrhythmias or clinical signs of hypokalemia. After termination of hyperventilation, serum K was slower to return to control values than PaCO2. The ratio of the duration of hyperventilation to the time required for return of serum K to control was 0.67. PMID- 2105556 TI - Heterogeneity of basement membranes in normal and pathologically altered tissues. PMID- 2105557 TI - Functional variations in liver tissue during the implantation process of metastatic tumour cells. AB - We have examined several properties of sinusoidal cells in the unaffected tissue of micrometastasis-containing livers. Tumour cells from either B16 melanoma (B16F10) or Lewis lung carcinoma (LLC) were injected intrasplenically in syngeneic mice and sacrificed on the 7th day. Light and scanning electron microscopy (SEM) showed tumour cells in hepatic veins and sinusoids in close contact with endothelial walls and macrophages. Following quantitative analysis of SEM images from sinusoidal walls it was found that endothelial fenestrae from B16F10 or LLC-colonized livers were diffusely reduced both in size and density/microns 2 throughout the sinusoid wall, although especially affected zone 3 segments. Following the intrasplenic injection of 1 microns fluorescent latex particles 1 h prior to sacrifice of the mice a significant reduction of the latex particle uptake by sinusoidal cells was detected in B16F10-colonized livers (27% of controls) which was in contrast to the significant increase in LLC-colonized mice (180% of controls). Despite the focal character of the tumour cell implantation process, hepatic sinusoidal cells reacted diffusely to metastatic cells. However, over liver acini, endothelial cell changes were mainly expressed in zone 3 while phagocytic properties mainly varied in zone 1 and depending on the tumour type. Although the significance of these sinusoidal changes on metastatic development is unclear, data suggests that "soil" conditions in the liver are different before and after being metastasized by tumour cells. PMID- 2105558 TI - A study by immunofluorescence microscopy of the NC1 domain of collagen type IV in glomerular basement membranes of two patients with hereditary nephritis. AB - The NC1 domain of the collagen type IV molecule, the major component of glomerular basement membranes (GBM), consists of dimers and 24 kilodalton (K), 26 K and 28 K monomers in man, and contains the Goodpasture antigen. Serum obtained from patients with Goodpasture's syndrome has been reported not to stain GBM of most male and some female patients with hereditary nephritis (HN) by immunofluorescence (IF) microscopy. In the present study, GBM seen on the renal biopsies of 2 patients (one male and one female) with HN were examined by IF to ascertain whether NC1 monomers were detectable. Three reagents were used: a plasmapheresis fluid (PPF) obtained from a patient who was treated for anti-GBM nephritis (human anti-GBM PPF); a commercial rabbit antibody against human NC1; and a rabbit antibody raised by us against dog NC1, which cross-reacted with human NC1. All 3 reagents detected NC1 determinants in GBM of normal human kidney by IF and reacted with human NC1 by a plate-binding radioimmunoassay (RIA). The human anti-GBM PPF bound to 28 K and 26 K monomer components of NC1 by Western blotting, the rabbit anti-human NC1 antibody bound to 26 K and 24 K monomers, while the rabbit anti-dog NC1 antibody bound only to the 26 K monomer. By IF, the human anti-GBM PPF did not stain GBM of the male patient with HN, but produced segmental staining of GBM (i.e., some GBM stained, while others did not) of the female patient. In contrast, the rabbit anti-NC1 antibodies produced global staining by IF of GBM of both patients. The absence of staining (i.e., global or segmental) seen with the human anti-GBM PPF implied that the 26 K and 28 K monomers of NC1 were either absent from GBM, or were present but altered structurally, leading to a diminution in their immunological reactivity. However, the positive staining observed with the rabbit anti-NC1 antibodies implied that the 26 K monomer was actually present in GBM. Hence, we postulate that the 26 K monomer of NC1 in GBM was structurally altered, and that the 28 K monomer was either absent, or present but altered. These findings suggest that there is an abnormality of more than one monomer of NC1 in GBM of patients with HN. PMID- 2105559 TI - Altered expression of Lewis blood group and related antigens in fetal, normal adult and malignant tissues of the uterine endometrium. AB - The expression of the Lewis blood group and its related antigens in fetal, normal adult and malignant tissues of the uterine endometrium was examined immunohistochemically using a panel of mouse monoclonal antibodies with specificities for Lewis-a (La), Sialyl Lewis-a (SLa), Lewis-b (Lb), Lewis-X (LX), Sialyl Lewis-X (SLX) and Lewis-Y (LY) antigens. La, SLa and SLX having one fucose residue were detected in a small number of fetal tissues, while Lb and LY having two fucose residues were found in most cases. In the adult endometrium, expression of Lb and LY was considerably lower than those in fetal tissues, although expression of La and SLa was not different between these two tissues. Expression of LX and SLX was pronounced in adult when compared with fetal tissues. Malignant endometrial glands expressed La, SLa, Lb and LY, extensively, while LX and SLX were expressed less than in normal tissues. Lb and LY can thus be considered oncofetal antigens, extensively expressed in fetal and malignant tissues but not in normal adult tissues. Expression of Lb and LY was greater than that of La and SLA in carcinoma; an increase in the activity of fucose transferase might be associated with malignant transformation in the uterine endometrium. PMID- 2105561 TI - Co-existence of two aneuploid stemlines in benign adenomas. PMID- 2105562 TI - Apparent failure of edetic acid chelation therapy for the treatment of coronary atherosclerosis. AB - Patients diagnosed with incurable or fatal diseases may seek alternatives to standard medical therapy and spend significant amounts of money for these therapies. One alternative medical therapy, chelation therapy with edetic acid (EDTA), has gained considerable popularity for the alleged treatment of atherosclerotic vascular disease; however, its efficacy for this indication remains unproven and its use is controversial. We present a case in which chelation therapy was unsuccessful in treating coronary atherosclerosis and review reports that substantiate a lack of efficacy using chelation therapy in the treatment of coronary atherosclerosis. Treatment of atherosclerotic-related diseases using chelation therapy should be discouraged by health professionals. Patients should be counseled regarding the risk of improper diagnosis and treatment of their disease. PMID- 2105560 TI - Cellular schwannoma. A clinicopathologic study of 29 cases. AB - A series of 29 cellular schwannomas is described in terms of their clinical presentation and course, light and electron-microscopic appearance, immunohistochemical properties and cytogenetics. The study indicates that cellular schwannoma can be defined as a subtype of classical schwannoma, characterized by spindle cells forming a compact fascicular, sometimes fibrosarcoma-like growth pattern, a low mitotic activity, a generally moderate nuclear and cellular polymorphism and a high degree of Schwann cell differentiation as seen by electron microscopy and immunohistochemistry. The tumour is characteristically located close to the vertebral column, in the mediastinum or retroperitoneum and has a benign course. Occasionally bone destruction and neurological symptoms develop. The clinical appearance together with the high cellularity, fascicular pattern and mitotic activity had led to the erroneous diagnosis of a soft tissue sarcoma in a few cases, and cellular schwannoma may thus be considered to be a pseudosarcoma. Immunohistochemically, cellular schwannomas appear to deviate from classical schwannomas and malignant peripheral nerve sheath tumours by their expression of glial fibrillary acidic protein. The chromosome analysis revealed a normal diploid stemline karyotype, with a variety of abnormal clones, including one with monosomy 22. PMID- 2105563 TI - Prospective controlled study of androgen effects on red cell oxygen transport and work capacity in chronic hemodialysis patients. AB - Effects of androgens on red blood cell (RBC) oxygen transport, RBC metabolism and work capacity in chronic hemodialysis patients were evaluated in a prospective controlled study. Compared to control subjects, patients given nandrolone decanoate had a sustained fall in RBC ATP and a transient rise in RBC DPG but P50 values were unchanged. Despite increases in RBC mass of 16-44% on androgen therapy, exercise on the treadmill improved in only 1 patient and actually declined in 3 others. Thus, these preliminary observations suggest that androgens may not improve hemoglobin-oxygen transport and that androgen-induced increases in red cell mass may only balance increased tissue oxygen requirements produced by these anabolic hormones. PMID- 2105564 TI - Comparative effects of busulfan, cytosine arabinoside and adriamycin on different maturation stages of normal human bone marrow cells. AB - Leukemic blast progenitors in acute myeloblastic leukemia (AML) undergo terminal divisions and/or self-renewal, which can be studied by the methylcellulose culture method and suspension culture, respectively. Using these methods, we have shown that busulfan (BU) was more effective against the self-renewal of blast progenitors than against the terminal divisions. As reported previously, cytosine arabinoside (Ara-C) is more effective against self-renewal and adriamycin (ADR) is more effective against terminal divisions. To determine the reason why antileukemic drugs show different sensitivity against self-renewal and terminal divisions, we studied the effects of these drugs on normal human bone marrow cells. We have shown that BU and Ara-C suppressed the colony formation induced by interleukin-3 (IL-3) more effectively than that by granulocyte colony-stimulating factor (G-CSF). On the other hand, ADR suppressed the colonies induced by G-CSF more effectively. In normal hemopoiesis, IL-3 has been shown to stimulate the growth of more primitive hemopoietic stem cells, while G-CSF has been documented to stimulate the growth of granulopoietic committed precursors at a more differentiated stage. Therefore, BU and Ara-C are considered to be more effective against the immature cells in normal bone marrow and ADR is effective against the more differentiated cells. We suppose that the different differentiation stage of target cells may explain the difference of the effects on self-renewal and terminal divisions between BU, Ara-C and ADR. PMID- 2105565 TI - Association of neutrophil alkaline phosphatase activity and glycosylated haemoglobin in diabetes mellitus. AB - We determined neutrophil alkaline phosphatase (NAP) activity in diabetic patients in conjunction with HbA1c levels. NAP was estimated using semiquantitative cytochemical technique, and we studied its activity in different groups of diabetic patients. We found that NAP score is correlated with the HbA1c level. Non-diabetic patients were used as controls, in whom NAP score and HbA1c were found normal. In diabetic patients the NAP activity and the HbA1c level were altered similarly during the various phases of the disease. Our findings indicate that NAP score could be used as a simple new parameter for diabetes. The pathophysiologic mechanism of our observations needs further investigation. PMID- 2105566 TI - Interleukin-2 inhibits growth of fibroblasts derived from human bone marrow. AB - The adherent layer that forms in human bone marrow suspension cultures contains fibroblast colonies which arise from colony-forming cells (CFU-F). We have demonstrated that recombinant interleukin-2 (r-IL2) inhibits growth of CFU-F by preventing their entry into S phase. This inhibition is not mediated by gamma interferon, nor by T lymphocytes, and can be abrogated by anti-IL2 receptor antibody. r-IL2 may influence haematopoiesis by its effect on bone marrow CFU-F. PMID- 2105567 TI - Chronic myeloid leukaemia in Yorkshire: a case control study. AB - The results of a case-control study of chronic myeloid leukaemia in adults are reported. 122 cases and 241 controls were interviewed. Excess risks associates with heart disease and related drugs were revealed. In addition a weak association with occupational and/or hobby exposure to irradiation emerged. PMID- 2105568 TI - A case of the unstable Hb Genova (beta 28 Leu----Pro) in an Arab child associated with severe haemolytic anaemia and growth retardation. AB - The first case of unstable Hb Genova from North Africa is described. It was found in a 13-year-old girl from Libya suffering from chronic Heinz body haemolytic anaemia and growth retardation. The available data strongly suggest that this case represents a new example for a spontaneous mutation. PMID- 2105569 TI - Sternal-manubrial separation as a complication of marrow aspiration in a patient with protein-calorie malnutrition and osteoporosis. AB - A simple needle aspiration of marrow from the sternum was performed in a middle aged woman with severe protein-calorie malnutrition and osteoporosis. Though carefully performed, a separation of the sternal-manubrial junction occurred with pain but no other serious sequelae. The subject of complications from marrow aspiration for diagnostic and therapeutic purposes is discussed. PMID- 2105570 TI - Spontaneous remission of agnogenic myeloid metaplasia in a splenectomized patient: a case report with erythrokinetic studies. AB - A 67-year-old woman with agnogenic myeloid metaplasia, who underwent splenectomy 1 year after the diagnosis, experienced spontaneous hematologic remission 6 years after splenectomy. Ten months before her anemia improved, peripheral leukocytes no longer showed a shift to the left and peripheral erythroblasts had disappeared. Sequential erythrokinetic studies revealed ineffective erythropoiesis with mild hemolysis and expansion of marrow activity in the tibia and femur but no erythropoiesis in the sacral or vertebral marrow. PMID- 2105571 TI - A case of congenital factor V deficiency combined with multiple congenital anomalies: successful management of palatoplasty. AB - A patient with congenital factor V deficiency combined with mental retardation and several congenital anomalies including cleft palate, dwarfism, microcephaly and right hydrocele testis is described. The levels of factor V activity and factor V antigen of plasma were significantly decreased. The platelet lysate obtained from him also showed a significantly low level of factor V activity. Palatoplasty and tooth extraction were successfully performed under transfusion therapy with fresh-frozen plasma. PMID- 2105572 TI - Megakaryoblastic transformation of essential thrombocythemia, hypercalcemia and lytic bone lesions. PMID- 2105573 TI - Current approaches to continuous insulin replacement for insulin-dependent diabetes: pancreas transplantation and pumps. PMID- 2105574 TI - Autologous transfusions. PMID- 2105575 TI - Drug-resistant hypertension. PMID- 2105576 TI - Functional role of tubuloglomerular feedback control of glomerular filtration. PMID- 2105577 TI - Glomerular function in diabetes mellitus. PMID- 2105578 TI - Nephrotoxicity of cyclosporine in autoimmune diseases. PMID- 2105579 TI - Recombinant human growth hormone (rhGH) treatment of children with renal insufficiency. PMID- 2105580 TI - Antineutrophil antibodies in vasculitis. AB - Antineutrophil cytoplasm antibodies appear highly specific to the primary systemic vasculitides, in particular to Wegener's granulomatosis and microscopic polyarteritis. Their occurrence in idiopathic crescentic rapidly progressive glomerulonephritis supports the view that this disorder may be regarded as a renal limited form of microscopic polyarteritis. The high sensitivity and specificity of ANCA detected using indirect immunofluorescence or solid phase techniques aids the primary diagnosis of these disorders; the measurement of ANCA may also be of value in long-term monitoring since disease relapse appears to occur only when ANCA are present, and it may therefore be inadvisable to withdraw immunosuppressive treatment until ANCA have been undetectable for extended periods of observation. However, the continued presence or reappearance of ANCA following initial induction of disease remission is not necessarily in concord with overt disease activity, although ANCA has been present in all patients in whom disease relapse has occurred. To understand further the role and relationship of ANCA to the vasculitic diseases requires elucidation of the autoantigen, and in this regard various neutrophil enzymes would appear to be likely candidates. Meanwhile, direct evidence of in vivo pathogenicity and studies of possible mechanisms of tissue injury, such as antiendothelial cell reactivity, are being sought. PMID- 2105581 TI - Recent advances in the pathogenesis of systemic lupus erythematosus. PMID- 2105583 TI - Sterile and pyrogen-free bicarbonate dialysate: a necessity for hemodialysis today. PMID- 2105582 TI - Immune deficiency of the uremic patient. PMID- 2105585 TI - The application of molecular genetics to the study of familial arterial hypertension. PMID- 2105584 TI - Endothelium-derived relaxing and contracting factors. PMID- 2105586 TI - Bacterial infections in chronic hemodialysis patients: epidemiologic and pathophysiologic aspects. PMID- 2105587 TI - Is renal transplantation useful for the understanding of the pathogenesis of hypertension? PMID- 2105588 TI - Mechanisms of atherosclerosis--a review. AB - The response-to-injury hypothesis of atherosclerosis takes into account interactions among all of the cells found in the lesions of human atherosclerosis, the cytokines and growth factors that can be formed by each of these cells (which are in fact formed in vitro and which have been demonstrated in vivo). It should therefore be possible to develop new diagnostic tools that will help us to make early diagnoses for patients who are at risk and determine the state of lesion formation in these patients. An intriguing question that remains is the role of the T lymphocytes in these lesions. The presence of these cells, and some early preliminary data, indicating that antigens unique to the lesions of atherosclerosis are present in the lesions, suggest that many of the lesions of atherosclerosis represent immune or autoimmune responses. The nature of the antigens, the response to these antigens, and the role of antigen-antibody complexes in the process of atherogenesis are important questions to be answered before we reach an understanding of this complex disease process that causes 50% of all deaths in the United States and Western Europe. PMID- 2105589 TI - CT diagnostic features of Alzheimer disease: importance of the choroidal/hippocampal fissure complex. AB - Neuropathologic changes in the temporal lobe, including focal atrophy of the subiculum and entorhinal cortex, have been described in association with Alzheimer disease. We studied the usefulness of detecting temporal-lobe structural changes on CT in making the diagnosis of Alzheimer disease. The dementia imaging protocol we use includes thin-section (5 mm) cuts of the temporal lobe oriented 20 degrees negative (caudal) to the plane of the canthomeatal line. Thirty-four patients with suspected Alzheimer disease and 20 normal elderly control subjects, all between 65 and 80 years old, were studied with a standard protocol that also included neurologic and medical examinations and detailed psychometric testing. All the temporal-lobe evaluations of the five variables measured were significantly associated with the presence or absence of Alzheimer disease. Almost all Alzheimer patients showed evidence of mild or greater severity of overall temporal-lobe atrophy. The absence of temporal-lobe atrophy, seen in approximately one half the normal cases, identified normal individuals with a high degree of specificity (95%). The presence of characteristic hippocampal lucency, apparently due to enlargement of the choroid and hippocampal fissures, showed the highest sensitivity and classification accuracy of all the variables tested (82 and 80% respectively; p less than .001), correctly identifying 82% of Alzheimer patients and 80% of Alzheimer patients and control subjects. These results indicate that CT detection of structural changes in the temporal lobe and hippocampus strongly support the diagnosis of Alzheimer disease. A temporal-lobe imaging protocol for CT, and by extension for MR, is suggested for the evaluation of patients with the clinical diagnosis of a dementing disorder. PMID- 2105590 TI - Intracranial ganglioglioma: MR, CT, and clinical findings in 18 patients. AB - Eighteen cases of pathologically proved intracranial gangliogliomas were reviewed to determine their MR, CT, and clinical characteristics. Seventeen patients were evaluated with contrast-enhanced CT and 14 were studied by MR imaging. Eight tumors were predominantly cystic; half of these demonstrated some contrast enhancement, and five contained calcifications. These cystic gangliogliomas were located, in order of decreasing frequency, in the cerebellum, temporal, frontal, and parietal lobes. Ten tumors were solid; eight of these showed contrast enhancement, and only one contained calcifications. Small cysts were present in one solid mass. Solid gangliogliomas occurred preferentially in the temporal lobes. On MR, the findings were nonspecific and reflected the CT findings. In one patient who received gadolinium-DTPA the lesion did not enhance. Clinically, all patients presented with nonfocal long-standing symptoms and all but three were alive an average of 18 months after the initial diagnosis. Pathologists are recognizing ganglioglioma with increasing frequency, and although its radiographic characteristics vary, it should be included in the differential diagnosis when the above-described findings are encountered. PMID- 2105591 TI - Primary cerebral neuroblastoma: CT and MR findings in 12 cases. AB - A retrospective CT, MR, and clinical study was performed in 12 patients, five children and seven adults, with histologically proved primary CNS neuroblastoma. The CT and MR appearances of these neoplasia were more variable than generally recognized. Although seven tumors were predominantly intraparenchymal masses with calcification and cyst formation, five were intra- or juxtaventricular. CT was preferable to noncontrast MR both at initial diagnosis and follow-up for identification of calcification, recurrent tumor at surgical sites, and leptomeningeal disease. Noncontrast MR was useful primarily for localization of peri- and intraventricular lesions. We conclude that primary CNS neuroblastoma has a more variable radiographic appearance than is generally recognized, and that an intra- or periventricular epicenter is common. PMID- 2105592 TI - CT and MR findings in patients with chordomas of the petrous apex. AB - Chordomas are rare neoplasms arising from remnants of the embryologic notochord. Although typically midline in site, intracranial tumors may arise off the midline, and a significant proportion of these arise unilaterally in the petrous bone. Three examples of this entity are presented, all demonstrating typical radiologic features. Dendritic branches of the cranial end of the notochord ramifying in the skull base are thought to provide the embryologic basis for this tumor. The CT and MR features demonstrated are similar to those of the more common midline chordomas. CT demonstrates a well-defined extraaxial soft-tissue mass associated with foci of calcification and bone destruction and occurring at a site corresponding with the embryologic distribution of notochordal material. On MR, prolonged T1 and T2 relaxation times result in hypointensity on T1 weighted images and marked hyperintensity on T2-weighted images. Signal voids result from the foci of calcification while hemorrhage may also lead to inhomogeneity. PMID- 2105593 TI - Increased density of the thalamus on CT scans in patients with GM2 gangliosidoses. AB - In 13 patients, the GM2 gangliosidoses, Sandhoff disease and Tay-Sachs disease, were found to be constantly associated with homogeneously and symmetrically increased CT attenuation within the thalami. In the only patient examined with MR imaging, a T2-weighted sequence showed hypointense thalami. It is suggested that this finding is caused by an accumulation of calcium, associated with the intracellular storage of GM2 ganglioside. The finding of dense thalami may be useful as a specific diagnostic criterion for GM2 gangliosidoses. In a few patients with blocks in adjacent steps in the sphingolipid metabolism, this finding was not present. PMID- 2105594 TI - The Sturge-Weber syndrome: comparison of MR and CT characteristics. AB - Four patients with Sturge-Weber syndrome were evaluated with CT and MR. MR demonstrated the characteristic features of the disease: cerebral atrophy (four patients), ipsilateral bone and sinus hypertrophy (three), ocular findings (one), intracranial calcification (four), prominent deep venous system (three), and enlarged choroid plexus (two). CT demonstrated the following: cerebral atrophy (four), ipsilateral bone and sinus hypertrophy (three), calcification (four), gyral enhancement (two), prominent deep venous system (two), and enlarged choroid plexuses (three). The features of Sturge-Weber syndrome were visualized equally well with MR and CT with the exception of intracranial calcification. Conventional spin-echo MR revealed fewer calcifications, and those visualized appeared smaller than with CT. Gradient-echo acquisition sequences were more effective in the detection of intracranial calcification. PMID- 2105595 TI - Malignant hyperphenylalaninemia: CT and MR of the brain. AB - A defect in biopterin synthesis not only prevents the transformation of phenylalanine to tyrosine (as in classical phenylketonuria, PKU) but also blocks the biosynthesis of the neurotransmitters dopamine, norepinephrine, and serotonin, causing severe neurologic disturbances. The brain CT and MR findings in this rare disorder have not been described. In the present series, eight patients with PKU were all examined with CT, three were also examined with MR imaging. In spite of severe clinical findings, CT was normal or almost normal in three patients; in three other children, moderate loss of brain volume was found. White matter disease was found in three patients (moderate in two and severe in one) and was also found in an additional patient with classical PKU. PKU should therefore be added to the list of possible causes for white matter disease. Furthermore, biopterin-dependent PKU should be considered when the CT examination in a child with severe neurologic manifestation only shows discrete pathology. PMID- 2105596 TI - CT of intracranial cryptococcosis. AB - CT scans of 35 patients with intracranial cryptococcal infection were reviewed retrospectively. Studies were normal in 43% of the patients. Positive findings in others included diffuse atrophy in 34%, mass lesions (cryptococcoma) in 11%, hydrocephalus in 9%, and diffuse cerebral edema in 3%. Two unusual types of cryptococcoma were encountered, namely gelatinous pseudocysts and an intraventricular cryptococcal cyst. All findings were nonspecific for CNS cryptococcosis. The results suggest that CNS cryptococcosis should be considered in all patients at risk for the disease who have these abnormal CT findings, no matter what their initial clinical presentation. In addition, MR demonstration of gelatinous pseudocysts in one patient indicates that this technique may be helpful in locating cryptococcal mass lesions not visualized on CT. PMID- 2105597 TI - Muscular and CNS effects of carotid artery administration of contrast media in rabbits. AB - Facial muscle twitching during intracarotid injections of nonionic contrast media has been observed in rabbits. To investigate the cause of this reaction, cortical EEG and facial EMG recordings were made from rabbits receiving selective internal and external carotid artery injections of control solutions (normal saline, mannitol), an ionic contrast medium (meglumine iothalamate), and three nonionic contrast media (iohexol, iopromide, and iotrolan). Internal carotid artery injections with all contrast media, both ionic and nonionic, produced ipsilateral EEG changes in 24 of 28 animals; however, ipsilateral EMG changes and visible twitching were observed only in animals injected with nonionic contrast media. Internal carotid artery injections with control ionic and nonionic solutions (physiological saline and mannitol, respectively) produced no EEG changes in any animals. Mannitol produced only ipsilateral EMG changes and visible twitching in most animals. The severity of the reaction to mannitol was generally less than that to the nonionic contrast media, and this difference was statistically significant when comparing mannitol with iohexol and iotrolan but not with iopromide. External carotid artery injections with nonionic solutions (contrast media and mannitol) produced significantly more severe ipsilateral EMG changes and visible twitching than were recorded with the internal carotid artery injections. Ionic solutions (contrast media and saline) had no effect. EEG changes were not observed after external carotid artery injection of any solution, with the exception of two of the seven animals injected with iotrolan. Angiography demonstrated retrograde filling of the external carotid arterial system from internal carotid artery injection via functioning orbital anastamoses. In contrast, internal carotid arterial vessels were not seen angiographically after external carotid artery injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105598 TI - MR imaging after surgery for vertebrobasilar aneurysm. AB - We examined the safety and utility of high-field MR in patients who had surgery for cerebral aneurysms of the vertebrobasilar system. Eighteen posterior (and three coincidental anterior) circulation aneurysms were treated. Twenty-one MR scans were obtained at a mean postoperative interval of 7.2 days. The mean size of the preoperative vertebrobasilar aneurysm was 2.2 cm; six were giant (greater than 2.5 cm) and eight were large (greater than 1.5, less than or equal to 2.5 cm). In 17 patients, Sugita nonmagnetic clips were used. In one other, a Drake tourniquet was used. No ill effects occurred from scanning with a high-field imaging unit at 1.5 T. The MR clip artifact was much less obtrusive than that on CT. In 11 cases, the aneurysm could be partially imaged postoperatively, mainly in very large aneurysms or in those treated by clipping the parent vessel. Of these, two revealed residual lumina on MR and nine looked completely thrombosed. Postoperative angiography showed that in four of the thrombosed-appearing aneurysms a residual lumen with a mean diameter of 1.0 cm had been missed. In the patient imaged after application of a Drake tourniquet, no artifact was seen, and a good assessment of progressive partial thrombosis was obtained. Evolution of the signal intensity of new aneurysm thrombus, in those minimally or not obscured by artifact, coincides with patterns previously described for hemoglobin in intracerebral hematomas. The earliest hyperintensity could be seen in either the periphery or the center of the new thrombus. All 15 patients examined with new postoperative deficits showed appropriate lesions, mainly small brainstem ischemic foci. Postoperative CT (performed in all but four of these patients) missed over 80% of these lesions, mainly owing to artifact from clip or bone. We conclude that MR is better than CT in the postoperative assessment of aneurysm patients, particularly in demonstrating small zones of ischemia. High-field MR scanning is safe if nonmagnetic surgical clips are used. MR is not accurate in assessing residual lumina. PMID- 2105599 TI - A new liquid material for embolization of arteriovenous malformations. AB - We have developed a liquid material for embolization of arteriovenous malformations that is a mixture of ethylene vinyl alcohol copolymer and metrizamide dissolved in dimethyl sulfoxide. Upon contact with blood, dimethyl sulfoxide rapidly diffuses into the blood and forms an ethylene vinyl alcohol copolymer elastic soft sponge that obstructs both the feeder and the nidus. The material, which is not adhesive, was used for embolization of three left cerebral arteriovenous malformations with satisfactory results. PMID- 2105600 TI - Intravascular microcatheter pressure monitoring: experimental results and early clinical evaluation. AB - With the use of Tracker and Balt microcatheter systems, intravascular pressure measurements were obtained in an experimental animal model, establishing the reliability of mean blood pressure measurements from these microcatheter systems. In the experimental model, selective occlusion of branches of the external carotid artery with simultaneous pressure measurements showed significant and reproducible changes in intravascular pressures. Also, pharmacologic manipulation of the blood pressure with simultaneous microcatheter and 6-French catheter recordings demonstrated an accurate and linear response of the microcatheter systems to mean blood pressure as it varied from 30 to 130 mm Hg. Preliminary results in humans with vascular malformations yielded similar results. We studied two cases of brain arteriovenous malformations (AVMs), one sigmoid-transverse sinus dural AVM, and one brain arteriovenous fistula (AVF). In these four cases the pressure dropped substantially, approaching the level of the shunt. In the case of the brain AVF, pressures rose in the same vessel after embolization. In the case of the dural AVM, correlation of the venous pouch pressures and the angiographic appearance indicated that shunting was no longer present when the venous and arterial pressures equalized. This system can be of substantial benefit in the evaluation and therapy of these lesions, and may increase our understanding of the physiology of vascular malformations. PMID- 2105601 TI - The diagnosis of herniated intervertebral disks with MR imaging: a comparison of gradient-refocused-echo and spin-echo pulse sequences. AB - Axial MR images of 65 lumbar disks with herniated nucleus pulposus imaged by gradient-refocused-echo (GRE) and spin-echo (SE) MR pulse sequences of 200-400/15 with a flip angle of 15-30 degrees was selected as optimal because of its high signal-to-noise ratio and good contrast between CSF, nucleus pulposus, and bone. The GRE technique was confirmed to be more sensitive in detecting prolapsed disks than the SE technique, but was less sensitive in demonstrating extruded disks. The combination of axial GRE and SE resulted in high detectability of herniated nucleus pulposus on axial MR images. Our results suggest that the GRE technique is an important adjunct to SE imaging in studying herniated nucleus pulposus. PMID- 2105602 TI - Effects of inhaled stable xenon on cerebral blood flow velocity. AB - The effects of inhaled stable xenon gas on cerebral blood flow were studied with 23 transcranial Doppler examinations performed in 13 normal volunteers while breathing, 25, 30, or 35% xenon for 5 min. Doppler velocities from the middle cerebral artery rose significantly during inhalation in 85% of subjects and 78% of studies and decreased significantly in 15% of subjects and 17% of studies. These different velocity responses may represent different responses of pial vasculature to xenon. The mean velocity rise among those studies showing a significant increase was 38 +/- 3.6% (SEM). The velocity rise began 2 min after the start of xenon inhalation and increased rapidly, so that the velocities measured at the four times at which scans were obtained in our xenon CT protocol (0, 1.5, 3, and 5 min after the start of xenon inhalation) were significantly different. A consistent fall in the pulsatility of the Doppler waveform as the velocity increased provided evidence for xenon-induced vasodilation of the small resistance vessels as the cause of the increase in flow velocity. Most subjects became mildly hyperventilated, so that the observed changes could not be attributed to hypercapnia. Inhalation of 25, 30, or 35% xenon for 5 min induces a delayed but significant rise in cerebral blood velocity. This suggests that cerebral blood flow itself may be rapidly changing during the process of xenon CT scanning. These changes may compromise the ability of the xenon CT technique to provide reliable quantitative measurements of cerebral blood flow. PMID- 2105603 TI - The relationship between frontal sinus drainage and osteomeatal complex disease: a CT study in 217 patients. AB - Over a period of 2 years we reviewed the CT scans of 217 patients with recurrent sinusitis. Our findings revealed a number of cases of osteomeatal complex disease with no frontal sinus involvement. This result is difficult to reconcile with the concept of a common drainage in the middle meatus shared by the frontal and anterior ethmoid sinuses. We conclude that the frontal sinus drains separately from the other paranasal sinuses in a large percentage of cases, and that the frontal sinus is frequently spared when there is ethmoid or maxillary sinusitis. PMID- 2105604 TI - Tumors of the nasopharynx and adjacent areas: MR imaging with Gd-DTPA. AB - The purpose of this study was to describe our experience with Gd-DTPA-enhanced MR imaging in the evaluation of the most common nasopharyngeal tumors. Forty-two patients with tumors of the nasopharynx and adjacent spaces had MR imaging before and after IV injection of Gd-DTPA. Images were obtained with a 1.0-T superconducting magnet imaging system in transverse, coronal, and sagittal planes with T1- and T2-weighted sequences. MR images were compared with CT scans and tumor histology. The studies were categorized by using a grading system with grades ranging from unsatisfactory (grade 0) to optimal (grade 3). Contrast enhanced MR enables better identification of small anatomic details such as both palatini muscles and the pharyngobasilar fascia. MR after Gd-DTPA was superior to CT in all cases except for tumors of the maxillary sinuses. MR with Gd-DTPA is recommended for tumors that are small and difficult to detect on the initial nonenhanced MR examination or that show subtle infiltrations. Because of the increased cost and longer examination time, MR with Gd-DTPA does not need to be done when large tumors are well delineated. PMID- 2105605 TI - MR imaging of pineocytoma: report of two cases. PMID- 2105606 TI - Demonstration of dural sinus occlusion by the use of MR angiography. PMID- 2105607 TI - MR imaging of choroid plexus lipomas. PMID- 2105608 TI - CSF fistula in a patient with Mondini deformity: demonstration by CT cisternography. PMID- 2105609 TI - Gd-DTPA-enhanced MR images: accentuation of vascular pulsation artifacts and correction by using gradient-moment nulling (MAST). PMID- 2105611 TI - Abstracts of the seventh annual Stowin Medical Conference--Endovascular interventional neuroradiology. Scarsdale, NY, July 10-12, 1989. PMID- 2105610 TI - Cerebral necrosis simulating an intraparenchymal tumor. PMID- 2105612 TI - The bright intervertebral disk: an indirect sign of abnormal spinal bone marrow on T1-weighted MR images. AB - Two phantoms were constructed and imaged for the purpose of reproducing and understanding the relatively increased signal intensity of intervertebral disks on T1-weighted MR images in three patients with diffuse vertebral metastases. The first phantom simulated a normal spine and showed that the disks and vertebral bodies were of similar intensity. The second phantom simulated an abnormal spine and showed that the disks were brighter than the vertebrae. Prolonged relaxation times from the vertebral bodies as well as manipulation of the window width and level are the factors responsible for the presence of bright disks on T1-weighted images. Variations in the window width and level can accentuate the apparent increase in signal intensity from the disks but not reverse it. Although the presence of bright disks may be subtle, recognition of this sign should raise the possibility of diffuse replacement of normal fatty bone marrow in the vertebrae. PMID- 2105613 TI - Age-related changes in the cervical facet joints: studies with cryomicrotomy, MR, and CT. AB - The cervical facet joints of 20 cadavers were studied systematically with MR, CT, cryomicrotomy, and histologic sections to determine the anatomic changes that occur with age. Uniform layers of cartilage and subarticular cortical bone characterize the cervical facet joints in cadavers under 20 years of age. Most adult cervical facet joints have only a discolored or microscopically thin layer of cartilage and have irregularly thickened subarticular cortical bone. The appearance of the cervical facet joints changes significantly with aging. PMID- 2105614 TI - High-resolution MR imaging of the cadaveric human spinal cord: normal anatomy. AB - The purpose of this study was to demonstrate the regional MR anatomy of a normal human spinal cord under near optimal conditions. A spinal cord and meninges were excised and segments from the cervical (C6), thoracic (T6), lumbar (L3), and sacral/cauda equina regions were examined on a 2-T MR system. By using a 2.5 x 2.0 cm solenoid coil and a multislice spin-echo sequence, we achieved a resolution of 58 microns in the readout direction and 117 microns in the phase encode direction. Histological sections corresponding to the areas imaged by MR were retained and treated with stains that demonstrated the distributions of collagen (hematoxylin, phloxine, saffron), myelin (Luxol fast blue/H and E), or neuritic processes (Bielschowsky's). Subarachnoid vascular, white matter, and gray matter structures were demonstrated by MR and light microscopy. The resulting MR images and photomicrographs were correlated. Different signal intensities were observed in the gracile and cuneate fasciculi, and these differences were similar to the pattern seen with the myelin stain. Decreased signal intensity was present in the region of the spinocerebellar tracts. The anatomic detail demonstrated by this study was clearly superior to that shown by clinical MR examinations. PMID- 2105615 TI - Lumbar disk herniation and canal stenosis: value of intraoperative sonography in diagnosis and surgical management. AB - One-hundred-four patients with preoperative diagnoses of lumbar canal stenosis, disk herniation, or a combination of both were evaluated with intraoperative sonography with the intent of (1) describing the sonographic characteristics of herniated disks and distinguishing these from bulging anuli, epidural fat, scar tissue, and spondylolisthesis; (2) establishing criteria for adequate decompression of canal stenosis; and (3) determining the usefulness of sonography in monitoring disk removal. Disk material demonstrates medium echogenicity, different in its sonographic features from bone, epidural fat, scar tissue, and epidural veins. A sonographic diagnosis of disk herniation was made in 43 cases, 41 of which were confirmed during surgery. Sonography established the presence or absence of disk herniation (confirmed by surgery) in 14 of 19 patients who had equivocal preoperative findings. After routine diskectomy, residual disk material was found in 17 (41%) of 41 patients, which led to further surgery in 16 patients with removal of the additional disk fragments. In 84 patients undergoing decompressive surgery for canal stenosis, sonography detected residual canal compression in 19 (23%), which led to a widened decompression in 15 of these patients. Sonography can differentiate disk material from other normal or abnormal structures in the canal; therefore, sonographic monitoring helps to ensure adequate bony decompression and complete diskectomy. We conclude that intraoperative sonography is an important tool in the surgical management of lumbar disk disease and stenosis. PMID- 2105616 TI - The cerebellum: 3. Anatomic-MR correlation in the coronal plane. AB - Thin (5-mm) coronal high-field (1.5-T) MR images of four human brain specimens and 14 normal volunteers were correlated with myelin-stained microtomic sections of the specimen cerebella. The primary white-matter tracts innervating several hemispheric (posterior quadrangular, superior, and inferior semilunar, gracile, biventer, tonsil) and vermian (declive, folium, tuber) lobules are oriented perpendicularly to the coronal plane of section and are shown well on proton density-weighted (long TR/short TE) and T2-weighted (long TR/long TE) spin-echo images, which provide excellent contrast between gray and white matter. Several of the surface sulci and fissures of the cerebellar hemispheres (including the superior posterior, horizontal, secondary, and posterolateral fissures) also course perpendicular to the coronal plane and are depicted well on T1-weighted (short TR/short TE) and T2-weighted images, which maximize contrast between CSF and parenchyma. The opportunity for side-to-side comparison of the hemispheres is a distinct advantage of the coronal view. Nevertheless, more obliquely oriented surfaces (preculminate, primary, inferior posterior, inferior anterior, and intrabiventral fissures) and deep hemispheric structures (primary white-matter tracts to central, anterior quadrangular, and floccular lobules) may be obscured by volume-averaging in the coronal plane; moreover, much of the finer anatomy of the vermis is depicted poorly. The constant surface and deep anatomy of the cerebellum revealed on coronal images in normal volunteers encourages detailed mapping. MR imaging in the coronal plane should be especially useful in identifying, localizing, and quantifying normal and abnormal morphologic differences between the cerebellar hemispheres. PMID- 2105617 TI - Hyperintense thrombus on GRASS MR images: potential pitfall in flow evaluation. AB - Gradient-recalled acquisition in the steady state (GRASS) MR images, obtained in four patients with angiographic evidence of successful occlusion of cerebral arteriovenous malformations, demonstrated hyperintense signal intraluminally. Although this was initially mistaken as evidence of persistent blood flow in the arteriovenous malformation, the short TR/TE spin-echo images showed hyperintense signal rather than flow void, thereby indicating the presence of subacute thrombus. GRASS images alone should not be used to determine the success of embolotherapy of cerebral arteriovenous malformations or to determine aneurysm patency, since the hyperintense signal is a potential pitfall that may mislead the radiologist in the absence of corroborative images, particularly the short TR/TE spin-echo sequences. PMID- 2105618 TI - The value of fast gradient-echo MR sequences in the evaluation of brain disease. AB - One-hundred-fifteen patients thought to have intracranial disease were studied with various two-dimensional short repetition time, partial-flip-angle gradient echo techniques: at 1.0 T, fast low-angle short (FLASH) at 10 degrees and 30 degrees and fast imaging with steady-state precession (FISP) at 60 degrees; at 1.5 T, FLASH 10 degrees, 30 degrees, and 60 degrees, FISP 60 degrees, and contrast-enhanced fast steady state at 60 degrees. These sequences were compared with a T2-weighted spin-echo sequence to determine the relative sensitivities of these techniques in detecting parenchymal lesions. Except for hemorrhagic lesions a substantial number of abnormalities were either not visible or poorly seen on the partial-flip-angle gradient-echo sequences. Minimizing echo time (6-9 msec) to decrease magnetic susceptibility effects did not improve lesion detection. Current usage of two-dimensional gradient-echo techniques for lesion detection is limited, except when calcification or hemorrhage is involved. Their utility may be expanded via the incorporation of three-dimensional techniques and IV contrast agents. PMID- 2105619 TI - Gd-DTPA-enhanced MR imaging of the brain in patients with meningitis: comparison with CT. AB - Plain and Gd-DTPA-enhanced MR images of the brain were obtained in 18 consecutive patients with meningitis (eight with tuberculous, five with bacterial, three with viral, and two with fungal infections); the MR images were compared with CT scans. MR images were obtained on a 2.0-T superconducting unit with both T1- and T2-weighted pulse sequences before injection and with a T1-weighted sequence after injection of Gd-DTPA (0.1 mmol/kg) in all patients. In tuberculous meningitis, MR imaging depicted ischemia/infarct, hemorrhagic infarct of basal ganglia, meningeal enhancement at either basal cistern or convexity surface of brain, and associated small granulomas in a few more patients than CT did. In bacterial meningitis, primary foci of extracranial inflammation (i.e., mastoid, paranasal sinuses) and adjacent intracranial lesions including localized dural inflammation, subdural fluid collection, and/or brain parenchymal lesions were demonstrated much better on MR than on CT. Otherwise, MR images generally matched the CT scan. Although the plain MR images, both T1- and T2-weighted, were the most sensitive in delineating ischemia/infarct, hemorrhage, and edema, they were not as specific as Gd-DTPA-enhanced T1-weighted images and postcontrast CT scans in defining the active inflammatory process of the meninges and focal lesions precisely. We conclude that if Gd-DTPA is used, MR imaging appears to be superior to CT in the evaluation of patients with suspected meningitis. Precontrast MR is needed to delineate ischemia/infarct, edema, and subacute hemorrhage. PMID- 2105620 TI - Half-Fourier MR imaging of CNS disease. AB - Three MR imaging techniques were compared in 37 CNS examinations. In each case, postprocessing of a single data set in three different ways was used for comparison. Eleven of the 37 patients had a clinical diagnosis of multiple sclerosis. The primary purpose of this investigation was to evaluate the quality of the half-Fourier imaging technique. With half-Fourier imaging, scan time can be reduced by approximately half without compromising spatial resolution. In T2 weighted examinations at 1.0 T (with present instrumentation), application of the half-Fourier technique leads to a decrease in lesion detectability in patients with multiple sclerosis: this is because there is a reduction in the signal difference-to-noise ratio of 32 +/- 11%. For T2-weighted screening of the CNS on high-field MR systems, with the exception of multiple sclerosis, half-Fourier imaging may offer a suitable compromise by decreasing scan time while preserving spatial resolution. Application of the half-Fourier method to T1-weighted techniques also results in diagnostic-quality images. PMID- 2105621 TI - Intracranial ependymoma and subependymoma: MR manifestations. AB - In order to provide a detailed description of the MR appearance of intracranial ependymoma, the MR examinations of 12 patients (10 with ependymomas and two with subependymomas) were reviewed and correlated with operative and pathologic reports. Three of 10 ependymomas were intraventricular, two were intraparenchymal, and five were transependymal, extending from CSF spaces into parenchyma. Both subependymomas were intraventricular. Solid ependymomas and subependymomas were iso- to hypointense relative to normal white matter on T1 weighted images and hyperintense on proton-density- and T2-weighted images. Foci of signal heterogeneity within solid neoplasms represented methemoglobin, hemosiderin, necrosis, calcification, and encased native vessels or tumor vascularity. Gd-DTPA-enhanced images in two patients differentiated enhancing tumor from surrounding nonenhancing edema and from surrounding normal brain parenchyma. Cystic neoplasms had sharply defined, round or oval margins and uniform signal intensity equivalent to or slightly hyperintense relative to CSF. Tumor-associated calcification was not demonstrated readily by MR. Sagittal and coronal images were valuable in assessing the amount of intraventricular tumor and route of extension. We conclude that the MR differentiation of ependymomas and subependymomas from other gliomas is provided most reliably by the location and morphology of the tumor and not by differences in signal intensity. The typical ependymoma arises within the fourth ventricle as a solid mass with heterogeneous signal intensity. A propensity for spread is seen along the CSF pathways via the foramina of Magendie and Luschka and the aqueduct of Sylvius. Supratentorial ependymomas may be periventricular in location and have cystic components. The two subependymomas in our series were solid, intraventricular tumors with relatively homogeneous signal intensities. PMID- 2105622 TI - A comparison of default and reduced bandwidth MR imaging of the spine at 1.5 T. AB - The value of a reduced bandwidth MR imaging technique was tested prospectively in 51 spinal MR examinations by using default (16 kHz) bandwidth, 2000/30, 90 (TR/TEs) and 600/30, and reduced (8 kHz) bandwidth, 2000/48, 92 and 600/30, techniques at 1.5 T. Bandwidth reduction was used to maintain the signal-to-noise ratio for a reduced scan time. Concerns have been raised as to the effect of bandwidth reduction at high field, since a savings in time or an increased signal to-noise ratio occur at the expense of increased chemical shift misregistration artifact. However, when appreciable, the chemical shift-related artifact in the spine was typically located in the frequency-encoding direction at the vertebral body/disk space interface or the dural sac/epidural fat interface in the lower lumbosacral region and was easily distinguished from pathologic lesions. There were no missed diagnoses with the reduced bandwidth technique. This study suggests that chemical shift-related artifact will rarely be confused with pathology by an experienced reader and suggests a clinical role for the bandwidth technique to decrease scanning time in uncooperative patients or to allow acquisition of additional imaging planes in a reasonable time. PMID- 2105623 TI - MR imaging in patients with intractable complex partial epileptic seizures. AB - Detailed neurologic studies, high-field-strength MR imaging, and CT scanning were performed preoperatively in 53 patients with intractable complex partial seizures who underwent surgical treatment for epilepsy. Macroscopic structural (tumoral or vascular) lesions were found in 28% of patients. The remainder had pathologic findings consistent with mesial temporal gliosis. Tumors were found in 22% of the patients and were benign or of low-grade malignancy in every case. MR was accurate in the preoperative diagnosis of structural lesions, including very small occult tumors and cryptic vascular malformations. In patients with mesial temporal gliosis, there was correlation between the MR observation of a unilaterally dilated anterior temporal horn and the EEG-identified seizure focus and side of temporal lobectomy. However, MR demonstrated T2-weighted signal abnormalities correlating with the epileptogenic focus in only 8% of cases of mesial temporal gliosis. MR provided useful information in 28% of patients who underwent surgery for refractory complex partial epilepsy. MR obviated invasive EEG monitoring in 93% of the patients with structural lesions. MR was useful in only 8% of the patients with pathologic changes of mesial temporal gliosis. PMID- 2105624 TI - Selegiline for Parkinson's disease. AB - Monoamine oxidase inhibitors that have been available in the United States are nonselective and thus act equally on peripheral and brain monoamine oxidase. Recently, selegiline, a selective monoamine oxidase inhibitor, has been approved for use in the management of Parkinson's disease. Clinical trials demonstrate that selegiline in combination with carbidopa/levodopa is effective in relieving symptoms and prolonging remission. The dosage of carbidopa/levodopa can usually be reduced, resulting in diminished side effects. Selegiline is relatively nontoxic and appears to be a valuable addition in the management of Parkinson's disease. PMID- 2105625 TI - Tissue plasminogen activator followed by percutaneous transluminal coronary angioplasty: one-year TIMI phase II pilot results. TIMI Investigators. AB - The TIMI phase II pilot study enrolled 288 patients with acute myocardial infarction who were treated with recombinant tissue plasminogen activator (rt-PA) within 4 hours of symptom onset and who were assigned to coronary angioplasty of the infarct-related vessel 18 to 48 hours after rt-PA treatment. The patients were followed to ascertain (1) vital status; (2) whether they suffered a recurrent myocardial infarction; (3) whether they received coronary angioplasty or bypass grafting; and (4) whether they were rehospitalized for a cardiac event. Risk factors for these events or combination of these events were identified and reported. The estimated 6-week, 6-month, and 1-year cumulative event rate of death or myocardial infarction was 9.1 +/- 1.7%, 12.9 +/- 2.0%, and 13.6 +/- 2.0%, respectively. With the exception of repeat hospital admissions, most of the above cardiac events occurred early during the patients' follow-up course. Cox proportional hazard analyses revealed that continuing chest pain after rt-PA administration, history of congestive heart failure, low systolic blood pressure at the time of initial evaluation, and history of hypertension increased the risk of death or recurrent myocardial infarction, while a history of chest discomfort at baseline evaluation and older age was predictive of future hospitalization or a revascularization procedure. PMID- 2105626 TI - Profound exacerbation of neuromuscular weakness by flecainide. PMID- 2105627 TI - Determinants of hospital charges for coronary artery bypass surgery: the economic consequences of postoperative complications. AB - This is a prospective study of 500 consecutive patients having coronary artery bypass surgery; mean hospital charge from time of surgery to discharge was +11,900 +/- 12,700. Multiple regression analysis was performed using preoperative variables and postoperative complications. No preoperative clinical feature was a significant predictor of higher average charge. Sternal wound infection (p = 0.0001), respiratory failure (p = 0.0001) and left ventricular failure (p = 0.017) were associated with higher average hospital charge. The absence of any complication predicted a lower average charge, and postoperative death (4.4 +/- 4.5 days after surgery) was also associated with lower average charge. A cost equation was developed: hospital charge equalled $11,217 + $41,559 of sternal wound infection, + $28,756 for respiratory failure, + $5,186 for left ventricular failure, - $1,798 for no complication and - $6,019 for death. Recognition of the influence of complications on charges suggests that low average charges can only be achieved by surgical programs with a low complication rate. PMID- 2105628 TI - Placental transfer of flecainide. PMID- 2105629 TI - Capillary blood gases in the neonate. A reassessment and review of the literature. AB - Heel puncture capillary blood gas (CBG) measurements continue to be used in neonates for estimating arterial blood gas values. Review of the literature reveals general agreement that CBG PO2 values are of little use in predicting arterial PO2 and that CBG pH values are reliable predictors of arterial pH; opinion varies regarding CBG PCO2. We conducted a two-part study comparing postductal arterial and CBG values. First, 50 infants were studied, each only once. All infants had umbilical arterial catheters in place. Blood was obtained simultaneously from the umbilical artery catheter and the warmed heels. Results demonstrated poor predictability of arterial values from CBG pH and PCO2 as well as for PO2. Second, to determine if variation both within and among individuals was similar, repeated measurements were made in 27 additional infants comparable to the first group. We obtained 3 to 28 simultaneous postductal arterial and CBG samples from each infant. A random-effects nested analysis of variance indicated that for pH, variation was largely the result of between-subject or within subject replicates effects, while for PO2 and PCO2, most variation was explained by differences between the two techniques (umbilical artery catheter vs CBG). The results indicate that CBG measurements do not accurately predict arterial values in neonates. Extreme caution should be used when management decisions are based on CBG values. PMID- 2105630 TI - Breath hydrogen excretion in the premature neonate. AB - We measured breath hydrogen excretion in 103 neonates from birth to as late as 2 months of age. The patients weighed less than 2000 g at birth and were part of a study of hydrogen excretion as a screening test for necrotizing enterocolitis. Hydrogen excretion in parts per million was normalized for the quality of the expired air by dividing by the Pco2 of the gas sample The rise in the H2/CO2 ratio was influenced by gestational age, energy intake, and antibiotic usage but not by the daily frequency of feeding. The mean +/- SD peak H2/CO2 ratio was 5.1 +/- 3.6 ppm per millimeter of mercury and occurred at 16.0 +/- 11.0 days of age. The age at which the peak H2/CO2 occurred varied with gestational age. Patients born between 23 and 28 weeks gestational age (n = 34) were 22.9 +/- 13.1 days of age when they experienced their peak H2/CO2 ratio, whereas those born between 29 and 34 weeks gestational age (n = 62) were 12.2 +/- 7.5 days of age. The age at which the peak H2/CO2 ratio occurred did not differ between these two groups when corrected for the age at which oral intake exceeded 420 kJ/kg per day. These results suggest that premature neonates require experience with ingesting more than 420 kJ/kg per day before bacteria and carbohydrates are present in large enough quantities to permit measurable hydrogen production. This information will be useful in future studies of premature gut development and physiology and in studying pathologic processes in which malabsorption may play a role. PMID- 2105631 TI - Hypothalamic hamartomas and sexual precocity. Evaluation of treatment options. AB - We describe four male patients with hypothalamic hamartomas associated with sexual precocity. Our assessment of their management suggests that resection using current microsurgical techniques is a valid treatment option if the patient has a normal pubertal endocrine makeup, if the hamartoma is pedunculated, and if the patient is young enough to require years of parenteral medical treatment. Such surgical treatment can be curative, and subsequent growth and development can be normal (patients 1 and 2). However, if the patient is near to pubertal age (patient 3) or if neurosurgical or gonadotropin releasing hormone analogue treatment is not available, the natural history (patient 4) suggests that the only undesirable effects are accelerated growth, tall stature for age, and premature sexual development during childhood, as well as the psychosocial problems that may accompany them. Adult height may be compromised, although the two patients who did not undergo a surgical procedure and did not receive gonadotropin releasing hormone analogue therapy are above the lower limits of the normal range of adult male height. Therefore, if the hamartoma is pedunculated and cessation of pubertal development is desired, resection of the hamartoma is a reasonable therapeutic option. PMID- 2105633 TI - Esophageal tuberculosis: definitive diagnosis by endoscopy. AB - This report describes a patient with a 2-wk history of epigastric pain and dysphagia, and a mid-esophageal ulceration resulting from infection with Mycobacterium tuberculosis. This is an uncommon site of tuberculous involvement, and usually results from direct extension from adjacent mediastinal or hilar lymph nodes, reactivated lung infection, infected vertebral bodies or aortic aneurysms, or from extension from the pharynx or larynx. The endoscopic lesion is ulcerative, with shallow, smooth edges, granular, with small mucosal miliary granulomas, or hyperplastic, with fibrosis, luminal narrowing, and stricture formation. The patient responded well to antituberculous therapy, and is healthy 4 yr after therapy. PMID- 2105632 TI - Measurement and demonstration of lactase and sucrase activities in jejunal mucosa. AB - Jejunal lactase and sucrase activities were demonstrated on endoscopically obtained biopsy specimens by a rapid test which had been developed earlier. The results were compared with enzyme activities found by Dahlquist's method. The data suggest that the rapid test is suitable for the semiquantitative determination of lactase and sucrase, and the results correlate with enzyme activities measured by the Dahlquist assay. The main advantage of the test is that it is rapid, simple, and cheap, and because no special equipment is necessary, it can be used in any endoscopic department. PMID- 2105634 TI - Orthotopic liver transplantation in a patient with combined hemophilia A and B. AB - A 38-year-old man with severe factor IX and mild factor VIII deficiencies complicated by cirrhosis secondary to chronic non-A non-B hepatitis underwent orthotopic liver transplantation as treatment for both the cirrhosis and his congenital coagulopathy. Intraoperative hemostasis was obtained with factor VII depleted prothrombin complex concentrate and fresh frozen plasma. Factor VIII and factor IX levels were assayed frequently in the perioperative period, and both returned to normal within 24 hr and remained normal postoperatively. Liver transplantation can be considered as definitive therapy for hemophilia A and/or B with transfusion-related liver disease. PMID- 2105635 TI - Prevalence of a shortened prostacyclin half-life in plasma in healthy adults: results of a screening investigation. AB - Out of a total of 1,981 adults (956 males, 1,025 females; aged 16-71 yr) undergoing a screening investigation for elevated cholesterol only 3 healthy participants with pathologically enhanced prostaglandin 12 (PG12) degradation in plasma in vitro were discovered. The PG12 half-life in these three screenings was shorter than 60 sec and persisted during several follow-up checks. In one patient a familial defect was discovered. Diseases known to be associated with this disturbance in PG12 metabolism have been excluded. The mean half-life of PG12 in 1,978 people amounted to 10.71 +/- 1.93 min. It still needs to be clarified whether this rare disturbance in PG12 metabolism is causally related to, or only associated with, thromboembolic events. A possible predisposition should be elucidated by regular monitoring of affected persons. PMID- 2105636 TI - Pure red cell aplasia following pernicious anemia. AB - A rare case of pure red cell aplasia (PRCA) in association with pernicious anemia is reported. A 40-year-old man presented with typical clinical and laboratory features of pernicious anemia and received intramuscular injections of vitamin B12, with satisfactory response. Anemia recurred 6 months later despite continued therapy, and the patient was noted to have PRCA, which was treated successfully with two courses of high-dose bolus methylprednisolone therapy. His peripheral mononuclear cells before the therapy suppressed colony formation of early erythroid precursors (BFU-E) from normal bone marrow; such a suppressive effect was not found after recovery from anemia. PMID- 2105637 TI - Induced expression of a monocytoid B lymphocyte antigen phenotype on the REH cell line. AB - A human common acute lymphoblastic leukemia (ALL) cell line, REH, was treated in vitro with gamma-interferon (gamma-IFN) or 12-O-tetradecanoylphorbol 13-acetate (TPA). Untreated (control) and treated cells were analyzed for changes in growth patterns, morphology, cytochemistry, surface phenotype, and terminal transferase (TdT) activity. TPA but not gamma-IFN induced further maturation of REH cells along the B-cell lineage. There was a dramatic decrease in CALLA expression, loss of TdT activity, induction of Leu M5, and increase in Leu 14 expression. TPA also induced monocytoid morphological features on REH cells. Enzymatically, the induced cells strongly expressed acid phosphatase (tartrate sensitive), alpha naphthol acetate esterase (NAE), and periodic acid Schiff (PAS). We conclude that TPA induced monocytoid B-lymphocyte features on REH cells within the B-cell lineage, which should not be confused with monocytes/macrophage. The phenotype of cells in this stage is Leu 14+, Leu M5+, BL1+, Leu 12+, AcP+, PAS+, NAE+, CALLA-, TdT-, MO1-, and MO2-. PMID- 2105638 TI - Sodium cromoglycate therapy in IgA nephropathy: a preliminary short-term trial. AB - Sodium cromoglycate (SCG), an antiallergic agent, is an effective drug in an experimental model for IgA nephropathy. The present report concerns a preliminary trial of patients with IgA nephropathy and proteinuria (greater than 1.0 g/d), which was conducted to determine the therapeutic value of SCG. Thirty patients were divided into two groups: one group (n = 15) was given oral SCG (1,200 mg/d) for 16 weeks after an observation of 4 weeks (SCG group), and the other group (n = 15) was observed without the changes of prescription (control group). No fluctuations were noted in proteinuria during the observation period in both groups. Proteinuria in the SCG group slowly decreased throughout the time course; however, a significant reduction was observed at 16 weeks as compared with that of the control group. On the other hand, no significant changes were noted in creatinine clearance (Ccr), serum albumin (s-alb), serum IgA (s-IgA), and IgA-CIC between groups. Five of 15 patients, designated "responders", showed a reduction in proteinuria of more than 50% of the pre-value (average value of observations period). The responder and nonresponder groups were comparable in clinical and histopathological data at the beginning of the trial. Nevertheless, no significant correlations arose concerning any point. Short-term SCG therapy may be beneficial in reducing proteinuria in some patients with IgA nephropathy. Allergic reactions may participate in the pathogenesis of this disease. PMID- 2105639 TI - Encainide-induced encephalopathy in a patient with chronic renal failure. AB - A report of encainide-induced encephalopathy in a patient with chronic renal failure is presented. Drug encephalopathy has been previously reported with various agents, but not with encainide. The patient improved after withdrawal of encainide. PMID- 2105640 TI - Renal changes in heterozygous Fabry's disease--a family study. AB - Two sisters, one with a long history of proteinuria and the other of hematuria, came for examination. Physical examination and routine laboratory workups did not show any significant abnormalities. The renal ultrastructural changes in case 1 showed marked enlargement and foamy vacuolation of all the glomerular capillary visceral epithelial cells, which was not found in other glomerular cells. The renal changes in case 2 showed similar lesions but with fewer cells involved and also with less severity, but the involved cells showed marked lamellation within the vacuoles. The serum alpha-galactosidase activity was 4.9 and 3.0 nmol/h/mL serum, respectively (normal values, 12.1 +/- 1.6 nmol/h/mL serum, mean +/- SD, n = 11), thus confirming the heterozygous variety of Fabry's disease. Our findings in these two cases reveal that patients with heterozygous Fabry's disease may present with renal symptoms only, which may be either proteinuria or hematuria. PMID- 2105641 TI - Flanking markers bracket the neurofibromatosis type 2 (NF2) gene on chromosome 22. AB - Neurofibromatosis 2 or bilateral acoustic neurofibromatosis (NF2) is a severe autosomal dominant disorder characterized by the development of multiple tumors of the nervous system, including meningiomas, gliomas, neurofibromas, ependymomas, and particularly acoustic neuromas. Polymorphic DNA markers have revealed frequent loss of one copy of chromosome 22 in the tumor types associated with NF2. Family studies have demonstrated that the primary defect in NF2 is linked to DNA markers on chromosome 22, suggesting that it involves inactivation of a tumor suppressor gene. We have employed a combination of multipoint linkage analysis and examination of deletions in primary tumor specimens to precisely map the NF2 locus between flanking polymorphic DNA markers on chromosome 22. The 13 cM region bracketed by these markers corresponds to 13% of the genetic length of the long arm of chromosome 22 and is expected to contain less than 5 x 10(6) bp of DNA. The delineation of flanking markers for NF2 should permit accurate presymptomatic and prenatal diagnosis for the disorder and greatly facilitate efforts to isolate the defective gene on the basis of its location. PMID- 2105642 TI - Interethnic genetic differentiation: GM polymorphism in eastern Senegal. AB - Analysis of GM polymorphism has been performed on 1,806 individuals representing three sympatric ethnic groups--Bedik, Fulani, and Mandenkalu--of eastern Senegal. Haplotype frequencies estimated by maximum likelihood have been used to compute common genetic pools between the three samples and a number of other sub-Saharan African populations. Despite extreme linguistic and sociocultural differentiations and very high levels of endogamy, especially in the Bedik and Niokholo Mandenkalu, the three populations share about 90%-95% of their haplotype frequencies in a system which commonly provides strong genetic differentiations. This supports the view that, despite its importance at a large continental scale level, as it is discussed for a set of populations from many regions of sub Saharan Africa, sociocultural differentiation usually has little effect on local genetic diversity. PMID- 2105643 TI - Correlation between lupus anticoagulants and anticardiolipin antibodies in patients with prolonged activated partial thromboplastin times. AB - PURPOSE: An increased incidence of thrombosis has been reported in patients with a prolonged activated partial thromboplastin time (APTT) due to a lupus anticoagulant (LA), which is an antibody to negatively charged phospholipids. The antiphospholipid antibodies can be quantitated in an enzyme-linked immunoabsorbent assay (ELISA) that utilizes cardiolipin as the antigen. With the development of the ELISA, two major areas of controversy have arisen. First, the correlation between assay results for LA and for the ELISA has varied widely among laboratories. Second, some investigators have described a correlation between high levels of anticardiolipin antibodies (ACA) and thrombotic disorders, whereas others have found no association between ACA levels and thrombosis in a general population of medical patients. To explore these issues further, the present study determined the sensitivity and specificity of an LA assay for detecting ACA in medical patients with a prolonged APTT. The association between the isotype and titer of ACA and thrombosis was examined in those patients positive for LA. PATIENTS AND METHODS: Plasma samples from 70 medical patients with a prolonged APTT by routine screening studies were tested for the presence of LA by dilution of phospholipid in an APTT system and for IgM and IgG ACA according to a standardized ELISA. Clinical records were reviewed for a history of thrombotic events by an investigator who had no knowledge of the laboratory results. RESULTS: The ACA assay gave positive results in 47 patients, 44 of whom also tested positive for LA. Thus, the sensitivity for the LA assay for detecting ACA was 94% (confidence interval, 82% to 99%). The result of the LA assay was negative in 20 of 23 patients who were ACA-negative. The specificity of the LA assay was 87% (confidence interval, 67% to 98%). Twelve of the 47 patients (26%) had a history of venous or arterial thrombosis. Of these patients, 75% tested in the high-positive range for IgG or IgM ACA, or both. Of the 35 patients without thrombosis, only 14% were in this range. Patients with thrombosis had either underlying systemic lupus erythematosus, lymphoma, or no apparent etiology for LA. There was no history of thrombosis in patients with LA associated with infection or medication. CONCLUSION: A test for LA in medical patients with a prolonged APTT can be sensitive and specific for ACA. Determination of ACA levels in patients who have LA that is not induced by medication or infection may define those patients at increased risk for thrombosis. PMID- 2105644 TI - Deficient tissue plasminogen activator release and normal tissue plasminogen activator inhibitor in a patient with recurrent deep vein thrombosis. PMID- 2105645 TI - Diarrhea with enteral feeding: will the real cause please stand up? PMID- 2105646 TI - Diarrhea in tube-fed patients: feeding formula not necessarily the cause. AB - PURPOSE: This study of diarrhea in tube-fed patients was undertaken to determine the proportion of cases in which feeding formula is not responsible for the diarrhea, the causes other than the feeding formula, and the diagnostic approach to diarrhea in tube-fed patients. PATIENTS AND METHODS: Inpatients at the Truman Memorial Veterans Hospital who received nasoenteric feeding during the time period from October 1986 through May 1988 were eligible for this study. Of 123 patients who received nasoenteric feeding, 32 patients had documented diarrhea (greater than 500 mL per day for at least two consecutive days) and were enrolled. Three of these patients received hypertonic feeding formula, whereas the remaining 29 received isotonic feeding formula. Prospective determinations of the causes of diarrhea were performed. Laboratory tests included fecal leukocytes, stool osmolality, stool electrolytes, and Clostridium difficile toxin assay. Diarrhea was considered osmotic if the stool osmotic gap was greater than 100 mmol/L. Clinical management involved reducing or stopping the feeding formula, stopping suspected medications, or administering appropriate antibiotics. RESULTS: There were 32 episodes of diarrhea in tube-fed patients during the study period. A single cause could be specified in 29 cases. The tube feeding formula was responsible for diarrhea in only 21% of these cases. Medications were directly responsible in 61% and C. difficile in 17% of cases. Stool osmotic gap correctly distinguished osmotic from non-osmotic diarrhea in all cases. CONCLUSION: When diarrhea develops in properly tube-fed patients, the feeding formula is usually not responsible for the diarrhea. Patients receiving nasoenteric tube feeding are frequently placed on liquid forms of medications. Many medicinal elixirs contain sorbitol, which is often the cause of diarrhea in tube-fed patients. Review of the medications and determination of the stool osmotic gap are the initial diagnostic steps of highest yield. PMID- 2105648 TI - Prediction of fetal anemia by measurement of the mean blood velocity in the fetal aorta. AB - In 68 red blood cell isoimmunized pregnancies the mean velocity of blood in the fetal aorta was measured by pulsed Doppler ultrasonography, and the fetal hemoglobin concentration was determined in blood samples obtained by cordocentesis. The values were compared to reference ranges of mean aortic velocity and hemoglobin for gestation, which were determined from 218 218 pregnancies that were not complicated by fetal hemolysis. In the red blood cell isoimmunized pregnancies there was a significant positive correlation between the aortic mean velocity and the hemoglobin deficit for the nonhydropic fetuses and a significant negative correlation between these two parameters for the hydropic fetuses. PMID- 2105647 TI - Three different schedules of low-density lipoprotein apheresis compared with plasmapheresis in patients with homozygous familial hypercholesterolemia. AB - PURPOSE: To determine the biochemical and clinical response of two patients with homozygous familial hypercholesterolemia to three different schedules of low density lipoprotein apheresis compared with plasmapheresis. PATIENTS AND METHODS: Two female patients aged 17 years, both affected by homozygous familial hypercholesterolemia, underwent low-density lipoprotein apheresis using a dextran sulfate/cellulose affinity column on successive twice-weekly, weekly, and biweekly schedules. Plasmapheresis was carried out only at biweekly intervals. Plasma lipids and apolipoproteins A1 and B were assayed before and after each procedure. Cardiac status was assessed before and after the study. RESULTS: On schedule 1 of apheresis, the immediate post-procedure low-density lipoprotein cholesterol levels declined to 60 mg/100 dL plasma. Quasi-steady-state values of low-density lipoprotein cholesterol and apolipoprotein B were also markedly reduced, with levels approaching the upper limits of normal for age and sex. This response was attenuated as the intervals between procedures were prolonged. No advantage of low-density lipoprotein apheresis over plasmapheresis was observed during the biweekly protocol except that after plasmapheresis high-density lipoprotein cholesterol levels declined by 50% or more compared with less than 10% after apheresis. The latter procedure, especially on schedules 1 and 2, caused an increase in the quasi-steady-state concentrations of both high-density lipoprotein cholesterol and apolipoprotein A1. Thus, mean low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apolipoprotein B/apo A1 ratios were reduced by more than three- to four-fold during twice-weekly apheresis. Other laboratory parameters remained stable throughout except for iron and hemoglobin levels, which were reduced with both plasmapheresis and apheresis. Xanthomas regressed significantly in the one patient who had not been treated prior to the current trial. Cardiac changes were minor in both patients. CONCLUSION: Low-density lipoprotein apheresis proved safe and effective on an accelerated protocol as well as during more conventional schedules. Owing to its simplicity, selectivity, and safety, apheresis using a dextran-sulfate/cellulose column is possibly the optimum means currently available for the extracorporeal removal of low-density lipoprotein cholesterol. PMID- 2105649 TI - Management of isoimmunized pregnancy by use of intravascular techniques. PMID- 2105650 TI - Efficacy of management of isoimmunization with fetal umbilical blood sampling remains unproved. PMID- 2105651 TI - Normal intraocular pressure after a bone marrow transplant in glaucoma associated with mucopolysaccharidosis type I-H. PMID- 2105652 TI - Effects of NaCl, glucose, and aldose reductase inhibitors on cloning efficiency of renal medullary cells. AB - To analyze the effects of sorbitol accumulation on the survival and growth of epithelial cells from rabbit renal inner medulla, cloning efficiency (an index of cell viability) was measured at normal and high glucose and NaCl concentrations and when sorbitol accumulation was prevented by Tolrestat and Sorbinil, which inhibit aldose reductase. With PAP-HT25 cells grown to near confluence, high NaCl increases aldose reductase activity, causing enough rise in cell sorbitol concentration to balance most of the increased osmolality of the high extracellular NaCl. Inhibition of aldose reductase prevents both the increased enzyme activity and sorbitol accumulation in a dose-related manner. Paralleling this, colony-forming efficiency is not affected by the inhibitors at a normal NaCl concentration but is greatly reduced when extracellular NaCl is high. On the other hand, high glucose levels, as occur in diabetes, increase sorbitol content well above the concentration required for osmotic balance and inhibit colony forming efficiency. Under those conditions, aldose reductase inhibitors lower cell sorbitol and reverse (at 300-350 mosmol/kgH2O) or reduce (at 500-550 mosmol/kgH2O) the decrease in colony-forming efficiency caused by high glucose. Thus sorbitol accumulation is necessary for osmoregulation when induced by high osmolality but is harmful when induced by high glucose. PMID- 2105653 TI - Effects of phlorizin and sodium on glucose-elicited alterations of cell junctions in intestinal epithelia. AB - Glucose alters absorptive cell tight junction structure and, as deduced from an impedance analysis model, diminishes tight junction resistance in the small intestine (J.R. Pappenheimer, J. Membr. Biol. 100: 137-148, 1987; and J.L. Madara and J.R. Pappenheimer, J. Membr. Biol. 100: 149-164, 1987). Here we provide further evidence in support of this hypothesis using the conventional approach of analysis of mucosal sheets mounted in Ussing chambers. This approach offers advantages for investigating underlying mechanisms, including the effects of ions and inhibitors on the regulation of intercellular junctions by glucose. We show that phlorizin blocks a resistance decrease elicited by glucose and demonstrate that substitution of choline for sodium also prevents the response. The dilatations in absorptive cell tight junctions that accompany this glucose elicited response are similarly prevented by phlorizin exposure or sodium substitution. The effects of phlorizin on junctional permeability can also be demonstrated in vivo. Phlorizin reduces the transjunctional flux of creatinine in glucose-perfused intestines of anesthetized animals, even when account is taken of the reduction of fluid absorption caused by phlorizin. Last, in vivo perfusion studies suggest that although, at 25 mM luminal glucose, virtually all glucose absorption is transcellular, at a luminal glucose concentration of 125 mM approximately 30% of glucose absorption occurs paracellularly because of solvent drag across tight junctions of altered permeability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105654 TI - Effect of GTP gamma S on insulin binding and tyrosine phosphorylation in liver membranes and L6 muscle cells. AB - Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), a specific activator of G proteins, did not change the Kd nor total binding of [125I]insulin in plasma membranes from rat liver. Insulin did not alter GTP gamma 35S binding nor polypeptide ADP ribosylation in crude and plasma membranes catalyzed either intrinsically or by cholera toxin. In L6 muscle cells, insulin caused tyrosine phosphorylation of a polypeptide of Mr 160,000. Cell electroporation enabled testing of G protein action in this cellular system. Phosphorylation of the Mr 160,000 polypeptide in these permeabilized cells was insulin and ATP dependent but other small molecules or ionic gradients were not essential. The reaction could not be mimicked by the G protein agonist GTP gamma S nor inhibited by the G protein antagonist guanosine 5'-O-(2-thiodiphosphate) (GDP beta S). However, GTP gamma S effectively decreased insulin-mediated phosphorylation of this polypeptide. This suggests that the tyrosine kinase activity of the insulin receptor can be modulated by G protein agonists. It is concluded that cross talk between the insulin receptor and G proteins could not be demonstrated in isolated membranes by strategies that detect interactions between beta-adrenergic receptors and G proteins. In contrast, in permeabilized cells, G protein-mediated regulation of the insulin receptor kinase activity could be detected. PMID- 2105655 TI - Mechanisms underlying enhanced glycogenolysis in livers of 3,5,3' triiodothyronine-treated rats. AB - Rats trained on a diurnal controlled meal-feeding schedule and injected with a single dose of 3,5,3'-triiodothyronine (T3) failed to accumulate liver glycogen and incorporated less D-[6-3H]glucose into glycogen than normally observed during the feeding period. In the experimental group, the concentration of liver adenosine 3',5'-cyclic monophosphate (cAMP) did not fall during feeding and the pattern of activities of glycogen phosphorylase, glycogen synthase, and phosphorylase kinase remained conductive to glycogenolysis. Liver lysosomal alpha glucosidase activity normally fell during feeding periods. After T3 treatment the activities of alpha-glucosidase and two lysosomal cathepsins (B1 and D) were elevated. The evidence suggests that T3 may induce both liver phosphorylase kinase and lysosomal alpha-glucosidase. This outcome of T3 excess, in concert with previously described T3-inducible systems, provides a plausible explanation for the failure of glycogen accumulation in this experimental model. PMID- 2105656 TI - Dissociation of the effects of epinephrine and insulin on glucose and protein metabolism. AB - The separate and combined effects of insulin and epinephrine on leucine metabolism were examined in healthy young volunteers. Subjects participated in four experimental protocols: 1) euglycemic insulin clamp (+80 microU/ml), 2) epinephrine infusion (50 ng.kg-1.min-1) plus somatostatin with basal replacement of insulin and glucagon, 3) combined epinephrine (50 ng.kg-1.min-1) plus insulin (+80 microU/ml) infusion, and 4) epinephrine and somatostatin as in study 2 plus basal amino acid replacement. Studies were performed with a prime-continuous infusion of [1-14C]leucine and indirect calorimetry. Our results indicate that 1) hyperinsulinemia causes a generalized decrease in plasma amino acid concentrations, including leucine; 2) the reduction in plasma leucine concentration is primarily due to an inhibition of endogenous leucine flux; nonoxidative leucine disposal decreases after insulin infusion; 3) epinephrine, without change in plasma insulin concentration, reduces plasma amino acid levels; 4) combined epinephrine-insulin infusion causes a greater decrease in plasma amino levels than observed with either hormone alone; this is because of a greater inhibition of endogenous leucine flux; and 5) when basal amino acid concentrations are maintained constant with a balanced amino acid infusion, epinephrine inhibits the endogenous leucine flux. In conclusion, the present results do not provide support for the concept that epinephrine is a catabolic hormone with respect to amino acid-protein metabolism. In contrast, epinephrine markedly inhibits insulin-mediated glucose metabolism. PMID- 2105657 TI - Direct evaluation of acidification by rat testis and epididymis: role of carbonic anhydrase. AB - The present experiments have employed microelectrode techniques (pH and PCO2) and microcalorimetry (total CO2 concentration) to define parameters of acidification in specific structures of the rat testis and epididymis during control conditions and after administration of the carbonic anhydrase inhibitor acetazolamide (20 or 50 mg/kg). Values for in situ pH during control conditions in seminiferous tubules (ST; 6.96 +/- 0.01), proximal caput (PCP; 6.62 +/- 0.01), middle caput (MCP; 6.59 +/- 0.01), middle corpus (MCR; 7.10 +/- 0.02), and proximal cauda epididymidis (PCD; 6.85 +/- 0.01) were significantly more acidic than in testicular artery (TA; 7.36 +/- 0.01) or systemic arterial blood (SAB; 7.40 +/- 0.01) and did not change significantly after acetazolamide. In situ partial pressure of CO2 (PCO2) in TA (52.2 +/- 0.6 mmHg), ST (52.3 +/- 0.4 mmHg), PCP (52.9 +/- 0.4 mmHg), MCP (53.0 +/- 0.7 mmHg), MCR (53.4 +/- 0.4 mmHg), and PCD (52.4 +/- 0.4 mmHg) were indistinguishable from each other, but all values were significantly higher than SAB PCO2 (39.2 +/- 0.5 mmHg). Acetazolamide increased in situ PCO2 significantly in all structures except the MCR. The total CO2 concentration in normal ST fluid (10.7 +/- 0.5 mM) was significantly higher than in "primary" fluid (6.9 +/- 0.3 mM), and both values were well below TA (26.9 +/- 1.3 mM) or SAB (24.6 +/- 0.4 mM) total CO2 concentrations. In the epididymis, total CO2 concentrations were indistinguishable and not different from the value in primary fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105658 TI - Interleukin 6 stimulates hepatic glucose release from prelabeled glycogen pools. AB - Cytokines, derived from a wide variety of cell types, are now believed to initiate many of the physiological responses accompanying the inflammatory phase that follows either Gram-negative septicemia or thermal injury. Because hypoglycemia (after endotoxic challenge) and hyperglycemia (after thermal injury) represent well-characterized responses to these injuries, we sought to determine whether hepatic glycogen metabolism could be altered by specific cytokines. Cultured adult rat hepatocytes were prelabeled with [14C]glucose for 24 h, a procedure that resulted in the labeling of hepatic glycogen pools that subsequently could be depleted (with concomitant [14C]glucose release) by either glucagon or norepinephrine. After the addition of a highly concentrated human monocyte-conditioned medium (MCM) or various cytokines to these prelabeled cells, [14C]glucose release was stimulated by MCM and recombinant human interleukin 6 (IL-6) but was not stimulated by other cytokines tested. Furthermore, only antisera to IL-6 were capable of reducing the glucose-releasing factor activity found in MCM. These data therefore suggest a novel glucoregulatory role for IL-6. PMID- 2105659 TI - Hormonal stimulation of Ca2+ release from the perfused liver: effects of uncoupler. AB - Administration of vasopressin and glucagon evokes a transient release of Ca2+ from perfused livers. The Ca2+ is released from a pool that is depletable by the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Therefore, the mechanism of the FCCP-stimulated Ca2+ release was examined. The FCCP-stimulated Ca2+ release was associated with a decrease in ATP levels. In the presence of oligomycin, which blocked the FCCP-induced rapid ATP breakdown, FCCP did not release Ca2+ though it still stimulated respiration. The possibility that FCCP might indirectly cause a release of Ca2+ by lowering hepatic ATP was examined at two levels of organization: 1) in the whole organ, by perfusing livers with fructose, a compound that was shown previously to drastically lower ATP in the liver, and 2) in isolated microsomal vesicles by depleting ATP with glucose and hexokinase. Fructose evoked Ca2+ release from the perfused liver. Similarly, depletion of ATP by the addition of glucose and hexokinase evoked a rapid release of the accumulated Ca2+ from microsomal vesicles probably by the inhibition of the Ca2(+)-ATPase. These results demonstrate that the major mechanism by which FCCP releases Ca2+ in intact cells is by lowering ATP levels. PMID- 2105660 TI - Collecting tubule adaptation to respiratory acidosis induced in vivo. AB - To examine the effects of respiratory acidosis in vivo on the adaptation of acidification in the collecting tubule, New Zealand White rabbits were exposed to a 6.7% CO2-93.3% O2 gas mixture in an environmental chamber for 0, 6, 24, or 48 h before obtaining collecting tubules for in vitro study. These collecting tubules were then perfused and bathed in vitro in identical Krebs-Ringer bicarbonate solutions. After 1 h equilibration total CO2 flux (JtCO2) was measured. The urine pH of the rabbits fell, whereas the blood bicarbonate rose as CO2 exposure time increased. In cortical collecting tubules, JtCO2 in vitro correlated with length of animal exposure to hypercarbia (y = 1.14174 + 0.1437x, r = 0.57, P = 0.002), and with the blood bicarbonate of the animal (y = 26.8471 + 0.0858x, r = 0.59, P less than 0.05). In vitro JtCO2 in medullary collecting tubules from rabbits that had been in hypercarbic atmosphere for 48 h (23.2 +/- 4.9 pmol.mm-1.min-1) did not differ from JtCO2 in control tubules (25.0 +/- 3.2 pmol.mm-1.min-1, not significant). Thus the cortical collecting tubule exhibits an adaptive increase in JtCO2 in response to hypercarbia, whereas the medullary collecting tubule does not. PMID- 2105662 TI - Effect of protein intake on the autoregulation of renal blood flow. AB - Autoregulatory ability was evaluated in male Sprague-Dawley rats (200-250 g) fed either low protein (LP, 6%), high protein (HP, 50%), or standard rat chow (CON) for 2 wk. Renal perfusion pressure (RPP) was first raised above normal by bilateral ligation of the carotid arteries. LP rats exhibited normal autoregulatory behavior between 130 and 100 mmHg, whereas autoregulation in HP rats was impaired (autoregulation factor 100-130; HP 0.86 +/- 0.16, LP 0.38 +/- 0.07, and CON 0.39 +/- 0.04). Autoregulation studies were repeated in HP- and LP fed rats after administration of the cyclooxygenase inhibitors, meclofenamate and piroxicam. Cyclooxygenase inhibition did not significantly affect base-line hemodynamics but did restore the ability of the HP rat to autoregulate renal blood flow (RBF) at high RPP. (Autoregulation factor between 100 and 130 mmHg; HP 0.29 +/- 0.10, LP 0.19 +/- 0.07, P, NS). Thus an HP diet resulted in impaired autoregulation of RBF at high RPP, an effect that appears to be mediated by excessive production of vasodilatory prostaglandins. PMID- 2105661 TI - In vivo osmoregulation of aldose reductase mRNA, protein, and sorbitol in renal medulla. AB - Sorbitol accumulates in renal medullary cells by synthesis from glucose in a reaction catalyzed by aldose reductase. Medullary sodium and urea are high and vary with urinary concentration. Sorbitol varies similarly, consistent with its role as a compatible intracellular organic osmolyte. We measured renal medullary sodium, urea, sorbitol, aldose reductase (protein and activity), and aldose reductase mRNA in rats treated to change medullary sodium and urea. In untreated Brattleboro rats all measurements were low and increased after 7 days of treatment with arginine vasopressin. In contrast, when normal rats were water deprived for 3 days, urea increased out of proportion to sodium, and sorbitol, aldose reductase, and aldose reductase mRNA were unchanged. After 2 h of diuresis, normal rats had lower medullary sodium and urea and reduced mRNA and sorbitol; however aldose reductase did not change. These data are consistent with previous results from cultured cells in which altered extracellular sodium, but not urea, leads to rapid changes in aldose reductase mRNA and slow changes (days) in aldose reductase. In addition, acute decreases in extracellular sodium increase leakage of sorbitol from cells. We also confirm previous results showing medullary glycerophosphorylcholine correlates best with urea, whereas the sum of all compatible osmolytes correlates best with sodium. PMID- 2105663 TI - Cytosolic free calcium regulation in renal tubules from spontaneously hypertensive rats. AB - Cytosolic free calcium (Caf) was measured in isolated renal cortical tubules from spontaneously hypertensive rats (SHR) and age-matched control Wistar-Kyoto (WKY) rats to evaluate whether the onset of hypertension is associated with a change in Caf. At the same time, the cellular mechanism by which differences in Caf occur between these two strains of rats was examined. Caf was significantly lower in renal tubules from 4- to 5-wk (142 +/- 6 vs. 187 +/- 15 nM), 6- to 7-wk (138 +/- 15 vs. 187 +/- 8 nM), and 8- to 9-wk-old (161 +/- 5 vs. 216 +/- 9 nM) SHR compared with age-matched WKY. The lower Caf in SHR tubules was considered to be the result of either an increase in Ca efflux or a reduction in Ca permeability. To the extent that metabolic inhibitors increased Caf but did not alter the difference between SHR and WKY, a primary difference in Caf efflux was excluded. Conversely, when Ca permeability was altered, either with Ca ionophores or incubation in Ca-free medium, Caf changed in the appropriate direction and the difference between SHR and WKY was no longer apparent. These results demonstrate that 1) the previously reported increase in Caf in circulating cells is not a universal feature of hypertension and 2) the lower Caf in renal tubules from SHR appears to be related to a lower Ca permeability. Whether the differences in Caf between SHR and WKY is a permissive factor for the renal contribution to hypertension remains to be elucidated. PMID- 2105664 TI - Lipoproteins are inhibitors of endothelium-dependent relaxation of rabbit aorta. AB - The present study was performed to investigate plasma inhibitors of endothelium dependent relaxation other than hemoglobin and low-density lipoprotein (LDL). We purified an inhibitor that contained a protein of 28,000 Da from human plasma by ammonium sulfate precipitation and serial chromatography. NH2-terminal sequence analysis revealed the protein to be homologous with human apolipoprotein A-I (Apo A-I), a major apolipoprotein of high-density lipoprotein (HDL). Very low-density lipoprotein (VLDL), LDL, and HDL obtained from rabbit plasma reversed endothelium dependent relaxation of rabbit aorta induced by acetylcholine (ACh) and A23187 but did not inhibit relaxations induced by nitroglycerin or nitric oxide. These inhibitory activities were lost by delipidation of lipoproteins, and there were no differences in the inhibitory activity among these three lipoproteins on the basis of phospholipid concentration. Moreover, phospholipids such as phosphatidylcholine, phosphatidylinositol, and sphingomyelin reversed relaxations by ACh and A23187. Thus all lipoproteins inhibit endothelium-dependent relaxation, and this nonspecific inhibition seems to be due to the inhibition of production or release of endothelium-derived relaxing factor by phospholipids in the lipoprotein complex. PMID- 2105665 TI - Cyclooxygenase inhibition potentiates myogenic activity in skeletal muscle arterioles. AB - The proposition that arteriolar constriction to increased intravascular pressure is mediated through either the increased local production of an eicosanoid constrictor factor or decreased production of a dilating factor was examined. The myogenic response of arterioles was studied by enclosing anesthetized rats in an airtight Plexiglas box with the cremaster muscle exteriorized into a tissue bath containing Krebs solution. Microvascular responses were observed by video microscopy. The arteriolar response to a 20-mmHg increase in intravascular pressure was examined in the absence or presence of cyclooxygenase inhibition. In the absence of cyclooxygenase inhibition, second-order arterioles (2As) responded passively to increased pressure by distending to 107 +/- 1% of control diameter. In the presence of the indomethacin, 2As constricted to 79 +/- 5% of control. Third-order arterioles (3As) constricted to 47 +/- 8% of control without indomethacin and similarly to 33 +/- 4% with indomethacin. To test whether inhibitors of endothelium-derived relaxation factor would potentiate the myogenic response of 3As, methylene blue or gossypol was topically applied to the cremaster muscle. Neither inhibitor was found to augment the myogenic vasoconstriction; however, these inhibitors were observed to significantly reduce basal vascular tone. In comparison, the tonic local production of dilating prostaglandins appears to attenuate myogenic activity as demonstrated by the appearance of myogenic activity in the normally passive 2As when exposed to cyclooxygenase inhibitors. PMID- 2105666 TI - Spinal noradrenergic pathways and pressor responses to central angiotensin II. AB - We have investigated the contribution of spinal noradrenergic (NA) pathways to the central pressor effects of angiotensin II (ANG II) in conscious rabbits with intact baroreceptors and after sinoaortic denervation (SAD). Very low intracisternal (ic) doses of ANG II [half maximum dose (ED50) = 6 x 10(-15) mol] produced increases in mean arterial pressure (MAP) and decreases in heart rate. Pressor responses to intracisternal ANG II were markedly reduced by 100 pmol of the ANG II antagonist [( Sar1, Ile8] ANG II, ic) and by intravenous prazosin, suggesting that central activation of ANG II receptors increased sympathetic vasoconstrictor tone. After SAD, the rabbits exhibited a 900-fold increase in sensitivity to ANG II (i.e., responded to very much lower doses, ED50 = 5 x 10( 18) mol). Intraspinal 6-hydroxydopamine (6-OHDA) injections given 1 mo earlier did not alter dose-response curves in baroreceptor-intact rabbits. However, the SAD-induced increase in sensitivity to ANG II was not observed in rabbits with depletion of spinal NA pathways. The results suggest intracisternal administration of ANG II activates two functionally distinct pathways: 1) a very sensitive site that utilizes NA projections to the spinal cord, and 2) a less sensitive site that uses non-NA descending pathways. Under normal baroreceptor input the former pressor pathway is completely inhibited. Thus the role of the central renin-angiotensin system may be of greater physiological importance in conditions where the baroreflex is suppressed. PMID- 2105667 TI - Mechanisms of contracting action of oxyhemoglobin in isolated monkey and dog cerebral arteries. AB - Oxyhemoglobin (HbO2) produced a concentration-dependent contraction of monkey and dog cerebral artery strips, which was significantly attenuated by endothelium denudation. The contractile response was suppressed by treatment with indomethacin, aspirin, and diphloretin phosphate, a prostaglandin (PG) receptor antagonist. OKY 046, a thromboxane synthase inhibitor, attenuated both the contractions caused by HbO2 and PGF2 alpha. Contractions by arachidonic acid (AA) of the monkey arteries were markedly inhibited by indomethacin and moderately attenuated by endothelium denudation. Treatment with superoxide dismutase and catalase failed to reduce the response to HbO2 and AA. The median effective concentration of HbO2 in producing dog cerebral artery contraction was approximately 1,000 times as high as the median inhibitory concentration in inhibiting the effect of endothelium-derived relaxing factor (EDRF) released from dog femoral arteries in response to acetylcholine. It is concluded that contractions caused by HbO2 are not associated with suppression of EDRF released spontaneously from monkey and dog cerebral arteries, but with vasoconstrictor PGs released mainly from endothelium. Thromboxane A2, superoxide anions, and hydrogen peroxide do not appear to be involved. PMID- 2105668 TI - Somnogenic, pyrogenic, and hematologic effects of bacterial peptidoglycan. AB - Bacterial infections and certain muramyl peptides elicit a variety of pathophysiological effects including increases in body temperature and slow-wave sleep. Bacterial cell wall peptidoglycan is composed of muramyl peptides. To investigate the ability of isolated bacterial cell walls to enhance slow-wave sleep, rabbits were injected intravenously with cell walls isolated from Staphylococcus aureus or with soluble peptidoglycan prepared from Neisseria gonorrhoeae. These injections increased slow-wave sleep, electroencephalographic delta-wave amplitudes, and body temperature, reduced rapid-eye-movement sleep, and induced neutrophilia and lymphopenia. The somnogenic and pyrogenic effects of S. aureus cell walls developed within 1 h and persisted throughout the recording period. Injections of N. gonorrhoeae peptidoglycan induced similar effects but of larger magnitude and shorter duration. We conclude that peptidoglycan is a bacterial component that mediates the increased sleep observed during infectious disease. PMID- 2105669 TI - Stimulation of H+ secretion by CO2 in turtle bladder: role of intracellular pH, exocytosis, and calcium. AB - We studied the interaction of intracellular pH, exocytosis, and cell calcium on the stimulation of H+ secretion by CO2 in turtle bladder. Intracellular pH was continuously monitored by the fluorescent dye 6-carboxyfluorescein and exocytosis was monitored by the release of mucosal fluorescein dextran. The initial stimulation of H+ secretion by 1 or 5% CO2 added to the serosal solution was accompanied by a similar and temporally related increase in exocytosis. Furthermore, a decrease in intracellular pH seems necessary for the early increase in H+ secretion and exocytosis. Because calcium plays an important role in exocytosis, we measured intracellular calcium in isolated cells with the fluorescent dye quin2. An increase in intracellular calcium (from 50 to 100 nM) was observed in isolated turtle bladder epithelial cells gassed with 5% CO2. To further evaluate the role of intracellular calcium on H+ secretion and exocytosis we utilized agents that alter cell calcium such as trifluoperazine and lanthanum. In the presence of CO2 these agents blocked partially the increase in H+ secretion and exocytosis but did not affect the decrease in intracellular H+. In conclusion, exocytosis, intracellular pH, and intracellular calcium play a key role in mediating CO2-stimulated H+ secretion in the turtle bladder. PMID- 2105670 TI - Three-phase study of phlebitis in patients receiving peripheral intravenous hyperalimentation. AB - We found clinical phlebitis in 57 of 88 patients with peripheral hyperalimentation (65%). To determine if this was a problem common to all intravenous fluid therapy at our hospital, we performed a point-prevalence study. The prevalence of phlebitis in nonhyperalimentation intravenous patients was 18% (84 of 456 patients). We then performed a randomized, prospective, double-blind trial of sham versus standard in-line filters to determine if bacteria or filterable particulate matter was responsible for phlebitis in the peripheral hyperalimentation group. The standard-filter group had a phlebitis rate of 74% compared with 64% in the sham-filter group. We then eliminated in-line filters and replaced the standard glucose-based solution with a glycerol-based peripheral hyperalimentation solution. The phlebitis rate decreased from 68% to 27% (p less than 0.001). In conclusion, phlebitis in peripheral hyperalimentation patients was probably due to chemical properties of the peripheral hyperalimentation solution rather than bacteria or particulates. PMID- 2105671 TI - Colorimetric end-tidal carbon dioxide monitoring for tracheal intubation. AB - We evaluated a colorimetric end-tidal carbon dioxide (ETCO2) detector (FEF end tidal carbon dioxide detector, Fenem, New York, N.Y.) during 62 intubations in anesthetized patients who were hemodynamically stable. The intubations were performed during a drill that simulates difficult tracheal intubation and therefore is associated with an increased risk of esophageal intubation. Each intubation attempt was monitored by two anesthesiologists and a research assistant who together used chest auscultation, colorimetric ETCO2, and capnography to confirm tracheal intubation and detect esophageal intubation. The reliability of the monitors was compared with capnography. Colorimetric ETCO2 confirmed tracheal intubations and detected esophageal intubations 100% of the time, as judged by capnography. There were no false-positive or false-negative decisions based on endotracheal tube position; however, one equivocal color change occurred, which was caused by failure to inflate the endotracheal tube cuff. Colorimetric ETCO2 monitoring confirmed tracheal intubation more rapidly than did chest auscultation (P less than 0.001) or capnography (P less than 0.05), and detected esophageal intubation more rapidly than did chest auscultation (P less than 0.05) and as rapidly as capnography did. Confirmation of tracheal intubation was achieved earlier than detection of esophageal intubation with all three monitors (P less than 0.05). We conclude that colorimetric ETCO2 monitoring is a safe, reliable, rapid, simple, and portable method for determining endotracheal tube position for patients who are hemodynamically stable and should be recommended where capnography is not available. PMID- 2105672 TI - Normobaric pulmonary oxygen toxicity. PMID- 2105673 TI - Prophylactic oral naltrexone with epidural morphine: effect on adverse reactions and ventilatory responses to carbon dioxide. AB - The influence of two different doses of oral naltrexone on the adverse effects and the analgesia of epidural morphine were compared in a double-blind, placebo controlled study. Forty-five patients undergoing cesarean section were provided postoperative analgesia with 4 mg epidural morphine. Five minutes later they received 6 mg naltrexone, 9 mg naltrexone, or placebo as an oral solution. Pain relief was assessed by the Visual Analog Scale (VAS) and by direct questioning of the patients. Requirement for additional analgesics and side effects were noted. Respiratory effects of epidural morphine and naltrexone were assessed using the ventilatory responses to CO2 and by monitoring O2 saturation (Spo2) using pulse oximetry. All patients in the placebo group had adequate analgesia. One of the 15 patients who received naltrexone 6 mg had inadequate analgesia versus five of the 15 patients who received naltrexone 9 mg (P less than 0.05), 9 mg versus placebo. Ten patients (67%) in the placebo group had pruritus while no patient in the 6 mg naltrexone group and one patient in the 9 mg group experienced mild pruritus (P less than 0.05), placebo versus other two groups. The CO2 response slopes were depressed compared to control values from 6-16 h in the placebo group, from 6-12 h in the 6 mg naltrexone group. No significant depression was noted in the 9 mg naltrexone group. The authors conclude that oral naltrexone 6 mg significantly reduces the incidence of pruritus associated with epidural morphine without affecting analgesia and that 9 mg naltrexone is associated with shorter duration of analgesia than 6 mg naltrexone. PMID- 2105674 TI - Prostacyclin for the treatment of pulmonary hypertension in the adult respiratory distress syndrome: effects on pulmonary capillary pressure and ventilation perfusion distributions. AB - Nine patients who had developed pulmonary artery hypertension during the adult respiratory distress syndrome (ARDS) were treated with an infusion of prostacyclin (PGI2) (12.5-35.0 ng.kg-1.min-1). Whether PGI2 might decrease the pulmonary capillary pressure (PCP) obtained by analysis of the pulmonary artery occlusion pressure decay curve and improve systemic oxygen delivery was examined. Gas exchange alterations induced by PGI2 were analyzed by using the multiple inert gas elimination technique. PGI2 reduced the pulmonary artery pressure from 35.6 to 28.8 mmHg (P less than 0.001) and the PCP from 22.9 to 19.7 mmHg (P less than 0.01) without changing the contribution of the pulmonary venous resistance to the total pulmonary vascular resistance. The cardiac index increased from 4.2 to 5.7 1.min-1.m-2 (P less than 0.001) due to both increased stroke volume and heart rate. Despite a marked deterioration of ventilation-perfusion (VA/Q) matching with increased true intrapulmonary shunt flow from 28.6% to 38.6% (P less than 0.01) of the cardiac output, the PaO2 was unchanged due to increased mixed venous oxygen content indicated by an augmented mixed venous PO2 (from 37.0 to 41.9 mmHg, P less than 0.01). This caused a 35% (P less than 0.001) increase of the systemic oxygen delivery rate. Thus, short-term infusions of PGI2 reduced PAP and PCP without deleterious effects on arterial oxygenation in patients with ARDS. Hence, PGI2 may be useful to lower pulmonary vascular pressures in patients with ARDS. PMID- 2105675 TI - Effect of fenoterol hydrobromide and sodium cromoglycate individually and in combination on postexercise asthma. AB - A double-blind trial involving 20 asthmatic patients was carried out to test the effect of fenoterol and sodium cromoglycate alone and in combination on ventilatory function one hour after medication. The results show that fenoterol, whether alone or in combination with sodium cromoglycate, can increase the forced expiratory volume in one second (FEV1) by up to 25% both after rest and after exercise. No patient suffered a decrease in FEV1 using fenoterol, and at least 80% of them recorded an increase in ventilatory ability. Sodium cromoglycate was of no benefit in eliminating early reaction to exercise-induced asthma. PMID- 2105676 TI - Continuous intravenous terbutaline infusions for adult patients with status asthmaticus. AB - Since absorption of nebulized and subcutaneous terbutaline may be delayed or decreased during episodes of severe asthma, a preliminary trial of intravenous terbutaline was instituted in five adult patients with status asthmaticus. The terbutaline was administered as a bolus followed by a continuous infusion of 0.1 0.4 micrograms/kg/min. Although three patients may have received some improvement, the impact of intravenous terbutaline could not be distinguished from other concomitant therapy. All patients experienced tolerable adverse reactions. Further research to evaluate higher doses administered early in the hospital course and to determine receptor sensitivity needs to be conducted. PMID- 2105677 TI - A computerized audit of 15,009 emergency department records. AB - The text of 15,009 emergency department medical records was reviewed with the use of a computer program that detected the presence or absence of key words and phrases. The search focused on "trigger diagnoses," that is, any diagnoses associated with an above-average risk for an undetected but more serious condition. Included were the trigger diagnoses from the five high-risk areas of extremity laceration, epiglottitis, abdominal pain, meningitis, and myocardial infarction. The three kinds of medical records that were compared were handwritten records, records dictated and transcribed, and records created by a voice-activated word processor. From a risk management perspective, inclusion of critical pertinent positives and negatives was taken as an index of quality from a risk management perspective, and records created by a voice-activated word processor using real-time risk management prompts were superior to handwritten and dictated records. The computer holds promise as a vehicle to reduce the cost and frequency of malpractice risk in the ED and as a teaching tool to improve the quality of care. PMID- 2105678 TI - Organ and tissue procurement in the acute care setting: principles and practice- Part 2. AB - In this two-part series on organ and tissue procurement in the acute care setting, the procurement problem, cost-benefit analysis, organizational development and framework, approach to surviving relatives, public attitudes, and brain death certification were discussed in part 1 (January 1990). Part 2 examines evaluation, selection, maintenance, and management of the organ-tissue donor. It concludes with a discussion of disease transmission, controversial issues, and financial considerations relevant to the procurement process in the acute care setting. PMID- 2105679 TI - Vascular permeability and coagulation during Rickettsia rickettsii infection in dogs. AB - The vascular permeability of the ocular fundus, alterations in the coagulation system, and plasma concentrations of thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in dogs following intradermal inoculation with 5 x 10(5) TCID50 of Rickettsia rickettsii. Twenty four to 48 hours after the onset of fever and rickettsemia, multifocal areas of retinal vasculitis were evident, which corresponded to areas of altered vascular permeability demonstrated by fluorescein angiography. The number and intensity of retinal vessels with sodium fluorescein leakage peaked during the second week after inoculation, and retinal vascular permeability remained altered during the third week of infection, well past the phase of clinical and clinicopathologic recovery. Development of retinal vasculitic foci was associated with thrombocytopenia, increased concentrations of circulating fibrinogen, and slight prolongation of activated partial thromboplastin time. Increased concentrations of fibrin/fibrinogen degradation products were detected in 4 of 9 dogs. Despite the degree of vascular endothelial damage evident on fluorescein angiographic and histologic studies in these dogs, plasma TXB2 and 6-keto-PGF1 alpha concentrations were not increased. PMID- 2105680 TI - Thyroid function tests in euthyroid dogs treated with L-thyroxine. AB - The effects of treatment with L-thyroxine (1 mg/m2 of body surface/d, PO, for 8 weeks) on the thyroxine (T4) and triiodothyronine (T3) responses to thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) administration were determined in 10 euthyroid Beagles; 4 other dogs acted as controls. The TSH response test was performed before treatment and at weeks 2, 4, and 8 of treatment in all dogs and at 2 and 4 weeks after cessation of treatment in 6 dogs. The TRH response test was performed before treatment and at week 6 of treatment in all dogs and at 5 weeks after cessation of treatment in 6 dogs. Suppression of the T3 response to TSH was evident at treatment week 2, whereas the T4 response was suppressed at week 4 and remained suppressed for the duration of the study. Four weeks after stopping treatment, T4 and T3 responses to TSH in 2 dogs were within the hypothyroid range. The T4 response to TRH was completely suppressed after 6 weeks of thyroxine treatment, but returned to pretreatment values by 5 weeks after cessation of treatment. Suppression of thyroid and pituitary function is evident after administration of a replacement dose of L-thyroxine to euthyroid dogs. PMID- 2105681 TI - Evaluation of serologic and cellular immune responses of cattle to a nonlipopolysaccharide antigen from Brucella abortus. AB - Cows naturally infected with Brucella abortus developed antibody (Ab) responses to a nonlipopolysaccharide antigen (NLA) purified from B abortus strain 1119-3. Sera from strain 19-vaccinated cows did not have detectable amounts of Ab. Weak lymphoproliferative responses to NLA were observed in blood mononuclear cell suspensions obtained from infected cows. There was no evidence of NLA-specific lymphoproliferation in cell suspensions from healthy cows. Nonlipopolysaccharide antigen binding to bovine blood mononuclear cells was observed by antigen consumption assays and direct binding of radiolabeled antigen. Cells from infected cows bound less NLA than did cells from healthy cows when assays were conducted with intact blood mononuclear cell preparations (monocytes plus lymphocytes). Monocytes obtained from any group did not bind NLA. Purified B lymphocytes from infected and healthy vaccinated cows bound about 3 times more NLA than did T lymphocytes, but there were no apparent differences between the 2 groups in extent of binding. Results of the study indicate that bovine lymphocytes have binding sites for a NLA purified from B abortus strain 1119-3. PMID- 2105682 TI - Thrombolytic therapy in canine pulmonary embolism. Comparative effects of urokinase and recombinant tissue plasminogen activator. AB - We compared thrombolytic and pulmonary hemodynamic effects of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) in canine micropulmonary thromboembolism. Dogs were embolized with radioactive autologous blood clot to increase mean pulmonary artery pressure (from 13 to 34 mm Hg, p less than 0.005) and decrease cardiac output (2.5 to 1.6 L min, p less than 0.005). Four groups of six dogs were treated. We employed two doses of UK, 30,000 U/kg (UK30) and 60,000 U/kg (UK60), and two doses of rtPA, 1 mg/kg (rtPA1) and 2 mg/kg (rtPA2). Drugs were infused over 15 min. Rate and extent of pulmonary thrombolysis were assessed by continuously counting over both lung fields with a gamma camera. Compared with treatment with UK, both rtPA regimes significantly increased thrombolysis. Mean total pulmonary thrombolysis was 14 and 23% with UK30 and UK60, respectively, and 35 and 43% with rtPA1 and rtPA2. Corresponding to the increased thrombolysis, pulmonary hemodynamics improved most with rtPA. From 90 min to 3 h, pulmonary artery pressure was significantly lower with both rtPA regimes than with either UK regime. These results indicate, at least in the model employed, that compared with treatment with UK, pulmonary thrombolysis and corresponding hemodynamic improvement are greatest with rtPA. PMID- 2105683 TI - C3a57-77, a C-terminal peptide, causes thromboxane-dependent pulmonary vascular constriction in isolated perfused rat lungs. AB - Pulmonary hypertension occurs after the intravascular activation of complement. However, it is unclear which activated complement fragments are responsible for the pulmonary vascular constriction. We investigated the 21-carboxy-terminal peptide of C3a (C3a57-77) to see if it would cause pulmonary vascular constriction when infused into isolated buffer-perfused rat lungs. Injection of C3a57-77 (225 to 450 micrograms) caused mean pulmonary arterial pressure (Ppa) to rapidly increase. However, the response was transient, with Ppa returning to baseline within 10 min of its administration. C3a57-77 also resulted in an increase in lung effluent thromboxane B2 (TXB2), concomitant with the peak increase in Ppa. C3a57-77 did not affect the amount of 6-keto-PGF1 alpha in the same effluent samples. Indomethacin inhibited the C3a57-77-induced pulmonary artery pressor response and the associated TXB2 production. Indomethacin also decreased lung effluent 6-keto-PGF1 alpha. The thromboxane synthetase inhibitors CGS 13080 and U63,357 inhibited the C3a57-77-induced pulmonary artery pressor response and TXB2 production without affecting 6-keto-PGF1 alpha. These inhibitors did not inhibit pulmonary artery pressor responses to angiotensin II. Tachyphylaxis to C3a57-77 occurred because a second dose of C3a57-77 administered to the same lung failed to cause a pulmonary artery pressor response or TXB2 production. The loss of the pressor response was not due to a C3a57-77-induced decrease in pulmonary vascular responsiveness because pressor responses elicited by angiotensin II were not altered by lung contact with C3a57-77. Thus, C3a57-77 caused thromboxane-dependent pulmonary vascular constriction in isolated buffer perfused rat lungs. PMID- 2105684 TI - Analysis of refractory period after exercise and eucapnic voluntary hyperventilation challenge. AB - We compared specific airway conductance (SGaw) and the FEV1 after repetitive exercise or repetitive eucapnic voluntary hyperventilation (EVH) challenges. Replicate challenges were matched in terms of inspired air conditions and minute ventilations (VE) in order to determine the degree of refractoriness after each type of challenge in patients with exercise-induced asthma. Ten patients exercised or hyperventilated dry, room temperature air at matched VE on two study days. When the patients FEV1 had returned to 90% of baseline or better, or at 3.75 h if FEV, had not returned to 90% of baseline, patients repeated the identical exercise or the EVH challenge. Minimum FEV1 values expressed as a percent of predicted FEV1 after the first and second exercise challenges were 52 +/- 16 and 58 +/- 17, respectively, which were statistically different (p less than 0.001; paired t test). Minimum FEV1 values after the first and second EVH challenges were 52 +/- 13 and 59 +/- 9% of predicted, respectively, which were also statistically different (p less than 0.01; paired t test). Seven of 10 subjects demonstrated higher SGaw values after the second exercise challenge compared with the first challenge, whereas eight of 10 subjects showed higher SGaw values after the second EVH challenge compared with the first challenge. Paired t test analysis indicated that percent protection, measured by FEV1, was similar after either type of challenge. We conclude that replicate exercise or EVH challenges with similarly matched inspired air conditions and VE induce similar degrees of refractoriness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105685 TI - Correlative imaging of sphenoid dysplasia accompanying neurofibromatosis. AB - Experience with five cases of sphenoid dysplasia is collected and illustrated by plain film, computed tomography, and magnetic resonance imaging. Ancillary changes in the maxilla and mandible are shown. Paramount to the presentation are changes induced in the orbit resulting in a large superior orbital fissure with or without a meningeal cyst projecting through the fissure. Serial studies of one patient from birth through 5 years of age present the progressive nature of this abnormality. PMID- 2105686 TI - Epidemiology of murine typhus. PMID- 2105687 TI - Abandonment of patients by home health nursing agencies: an ethical analysis of the dilemma. PMID- 2105688 TI - Thinking upstream: nurturing a conceptual understanding of the societal context of health behavior. AB - This article addresses the issue of overreliance on theories that define nursing in terms of a one-to-one relationship at the expense of theoretical perspectives that emphasize the societal context of health. When individuals are perceived as the focus of nursing action, the nurse is likely to propose intervention strategies aimed at either changing the behaviors of the individual or modifying the individual's perceptions of the world. When nurses understand the social, political, and economic influences that shape the health of a society, they are more likely to recognize social action as a nursing role and work on behalf of populations. PMID- 2105689 TI - Postcolonial nursing education in Trinidad and Tobago. AB - In this article the impact of the developed nations on basic nursing education in Trinidad and Tobago in the postcolonial period is discussed and analyzed. Subsequent to self-government in 1956, the national government, in its efforts to become independent of its reliance on Great Britain, turned to the United States and Canada for technical and financial aid. Consequently, sources such as the World Bank, Inter-American Development Bank, Pan American Health Organization/World Health Organization, and the Canadian International Development Agency were major avenues for the provision of ideas, concepts, and values in health planning and policy making with primary health care endorsed by the government. Nursing education was thus influenced by these industrialized concepts and values. The impact of socioeconomic and nursing events in the Caribbean region coupled with local initiatives taken by the indigenous leadership to improve nursing education resulted in a program that was an amalgamation of British, North American, and indigenous features. PMID- 2105690 TI - Democratization of health care: challenge for nursing. AB - One of the key foundational principles of primary health care is community involvement. The implementation of meaningful community involvement requires democratic institutions and processes within the health care system. In this context the meaning of substantive democracy and the implications of this concept for the health care system are briefly discussed. The relationship between the purpose, values, and foundational concepts of democracy and those of nursing is examined in greater detail. Based on the congruency between these, the role of nursing in generating and enhancing democratic processes within the health care system is discussed and a model of nursing practice proposed. PMID- 2105691 TI - Is health care racist? AB - Many health care inequalities seem to be racially based. Racism nad racial conflict in American can be explained in the context of three historical time periods and the prevailing economic systems of those times. The problem of access to basic health care for the black underclass is enormous. Traditional solutions of health education, health promotion, and low-cost health care have done very little to change the outcomes of increased morbidity and mortality. Health care professionals need to confront the real problem of inadequate life chances and limited economic resources for the underclass through research and the restructuring of our health care delivery system. PMID- 2105692 TI - Psychologic health of women: a phenomenologic study of women's inner strength. AB - This article describes a phenomenologic research study of psychologic health--the inner strength of women. The research objective was to identify and to describe the meanings, qualities, and structures of the lived experiences of inner strength for women. Nine women were selected who acknowledged and articulated their subjective experience of inner strength. Data were generated using unstructured, in-depth, face-to-face interviews. Data analysis incorporated the methods of Colaizzi, van Manen, and Spiegelberg. The results revealed nine essential themes that add to the cumulative knowledge base of psychologic health by generating new meanings of the nature and essences of inner strength from female perspectives. PMID- 2105693 TI - Home care management in chronic illness and the self-care movement: an analysis of ideologies and economic processes influencing policy decisions. AB - Over the past few decades there has been an increasing trend toward self-care and home health care, and one would suspect that these trends will continue into the next century. This article addresses the policy issues that have arisen from a program of research with families caring for a child with a chronic illness in the home and with women who have diabetes mellitus. The argument is developed that, although the home care and self-care movements can be seen as directed toward providing more humanistic care and promoting the independence of the client, the economic and sociopolitical factors that influence their development should not be overlooked. Furthermore, the "cost of caring" must be reckoned with in both human and economic terms. Cost-effective care, in the long run, will mean care that takes into account the social context of health and illness. PMID- 2105694 TI - From provider to partner: a conceptual framework for nursing education based on primary health care premises. AB - An emerging need to educate nurses in innovative ways of working that respond to and interact with informal support networks was discerned. Accordingly, this study's purpose was to develop a conceptual framework for undergraduate nursing education that manifests a primary health care philosophy of consumer input and collaboration with lay helpers. This was predicated in part on a review of social support theoretic premises, other theories germane to social support, and existing conceptual frameworks for the nursing discipline. Sixteen assumptions were developed and the four components of nursing's metaparadigm were defined to reflect primary health care premises of professional partnership with laypersons. Twenty core concepts were derived from social-support supplementary theories. A connecting structure was developed through creation of 20 relationship statements and 2 figures. The framework was favorably, albeit tentatively, evaluated against preselected criteria. PMID- 2105695 TI - Predicting the health care issues of the future. PMID- 2105696 TI - Immobilization of glucose oxidase and peroxidase and their application in flow injection analysis for glucose in serum. AB - Glucose oxidase (GOD) and Horseradish peroxidase (HRP) were covalently coupled to alkylamine controlled pore glass by means of glutaraldehyde. About 700-800 U/g of immobilized GOD and 300-400 U/g of immobilized HRP were obtained. Some factors of affecting enzyme immobilization were discussed. The immobilized enzymes were packed into a plastic tube and used in flow-injection analysis (FIA) for glucose in serum. A good linearity range was observed for this immobilized enzyme system at 20 mg/mL to 1000 mg/dL D-glucose, the recovery was 95.4-103.5%, the within batch imprecision was 0.8-2.2%, and the between-batch imprecision was 2.2-4.2%. More than 100 samples were measured within an hour. One enzyme column with five units of immobilized GOD and HRP, applied for 50 assays/d, has been used for more than 2 mo. PMID- 2105697 TI - [Intraoperative intraperitoneal administration of CDDP against gastric cancer with peritoneal dissemination]. AB - This study was undertaken in order to evaluate the effect of intraoperative intraperitoneal (i.p.) administration of CDDP on patients who underwent gastrectomy for gastric cancer with peritoneal dissemination, compared with MMC or OK-432 i.p. administration group and untreated group. The median survival time was 11 months in CDDP i.p. group (35 patients), 8 months in MMC or OK-432 Ip group (33 patients) and 7 months in untreated group (25 patients). 1- and 2-year survival rates were 30.4% and 12.1% for MMC or OK-432 i.p. group, and 28% and 8% for untreated group, while in CDDP i.p. group, the rates were higher at 46.4% and 14.7%, respectively (CDDP i.p. group vs. untreated group, p less than 0.05). In vitro chemosensitivity test by succinate dehydrogenase inhibition (SDI) test supported the clinical results. CDDP had higher sensitivities than MMC and ADM on poorly differentiated cases as well as peritoneal dissemination cases. Our results suggest that intraoperative i.p. administration of CDDP was useful for the treatment of gastric cancer with peritoneal dissemination. PMID- 2105698 TI - [Clinical study of UFT chemotherapy in renal cancer. Kyushu University Cooperative Study Group of Renal Cancer]. AB - Clinical effects of UFT chemotherapy for renal cancer were evaluated by 19 collaborating hospitals. UFT (300-600 mg/day) was administered for more than 3 months. Of the 30 patients entered in this study, 21 were evaluable for the antitumor effects of the drug. Of the 21 evaluable patients, complete response (CR) was obtained in 2 patients, partial response (PR) in 1, no change (NC) in 7, progressive disease (PD) in 11, respectively. The response rate was 0% in patients with primary lesion and 21.4% in nephrectomized patients with metastatic lesion. Responses were observed in the metastases of lung, pleura and mediastinal lymph node. The main side effects in 27 patients were gastrointestinal symptoms. No significant abnormality was noted on blood laboratory data. In one patient the drug was discontinued within 3 months because of gastrointestinal symptoms. These results suggested that UFT chemotherapy for advanced renal cancer was clinically effective. PMID- 2105699 TI - [Experimental studies on subrenal capsule assay using cyclosporin A treated mice- the optimal treatment schedules of CsA and anticancer agents (mitomycin C and 5 fluorouracil)]. AB - We studied fundamentally subrenal capsule assay, using human tumor specimens (breast, gastric and colon cancers) serially transplanted in nude mice. When cancer anticancer agents such as mitomycin C (MMC) and 5-fluorouracil (5-FU) were injected into immunocompetent mice treated with various dosages of cyclosporin A (CsA) after tumor implantation, optimal schedule of each drug was examined on the points of effects and toxicity against host mice. The following results were obtained. Control groups were set up as immunocompetent mice which treated daily with 60 mg/kg CsA from day 1 after tumor implantation. Optimal treatment schedule was judged as MMC 3 mg/kg i.v. injection on day 1 following by daily 60 mg/kg CsA treatment, and 5-FU was injected 25 mg/kg subcutaneous injection every day from day 1 without CsA treatment, each schedule showed an appropriate anti-tumor activity profiles against implanted tumor xenografts, and had less toxicity to the hosts. PMID- 2105700 TI - Tissue plasminogen activator reverses the deleterious effect of infection on colonic wound healing. AB - Fibrin deposition in response to bacterial peritonitis appears to predispose to residual infection in the peritoneal cavity. Our previous studies have demonstrated that intraperitoneal fibrinolysis using human recombinant tissue plasminogen activator (t-PA) prevented abscess formation in a rat intra-abdominal sepsis model. To investigate the potential adverse side effects of its use in the peritoneal cavity, the effect of t-PA on colonic anastomotic wound healing and on systemic coagulation parameters was examined in the rat. T-PA did not adversely affect colonic healing five and ten days after anastomosis. In animals infected intraperitoneally at the time of the anastomosis, t-PA reversed the inhibition of healing induced by perianastomotic abscesses at five days. This effect was mediated by the ability of t-PA to prevent perianastomotic abscess formation. After intraperitoneal administration, t-PA had no effect on prothrombin and partial thromboplastin times in either uninfected or infected animals and there was no evidence of clinical bleeding related to its use. These studies suggest that intraperitoneal fibrinolysis using t-PA may provide a safe, effective form of adjuvant therapy in the management of fibrinopurulent peritonitis. PMID- 2105701 TI - Mesenteric traction syndrome. PMID- 2105702 TI - The effect of oral and parenteral typhoid vaccination on the rate of infection with Salmonella typhi and Salmonella paratyphi A among foreigners in Nepal. AB - We studied the incidence of enteric fever among travelers and foreign residents who attended an expatriate clinic in Kathmandu, Nepal, from February 1987 to June 1988. There were 42 cases of enteric fever; 20 were caused by Salmonella typhi and 22 by Salmonella paratyphi A. Among 18 unvaccinated foreigners who had enteric fever, S typhi was isolated from 67%, and S paratyphi A from 33%, a ratio similar to the local Nepalese population. Among 22 vaccinated foreigners, S typhi was isolated from 35%, compared with 65% with S paratyphi A. Nine percent of tourists had received the oral Ty21A typhoid vaccine. However, among seven vaccinated tourists who became infected with S typhi, four (57%) had received the oral vaccine. Typhoid vaccine efficacy for tourists was calculated and showed an overall protective rate of 90% against enteric fever in general, 95% protection against S typhi, and 72% to 75% protection against S paratyphi A. We conclude that typhoid vaccine should be recommended to all travelers to the Indian subcontinent, and since S paratyphi A is the predominant cause of enteric fever among vaccinated travelers, consideration should be given to an effective vaccine against S paratyphi A when that becomes available. PMID- 2105703 TI - Thyroglobulin measurement vs iodine 131 total-body scan for follow-up of well differentiated thyroid cancer. AB - Measurement of the serum thyroglobulin level may be more sensitive than total body scan using sodium iodide 131 for detecting recurrences from well differentiated thyroid cancer. We have evaluated the merit of these two methods through a retrospective chart review of patients followed up at the Milton S. Hershey Medical Center, Hershey, Pa. We found that in 17 (45%) of 38 follow-up visits, the presence of interfering antibodies prevented the measurement of serum thyroglobulin levels. Furthermore, such determination was less sensitive than iodine 131 total-body scan in detecting residual thyroid tissue and/or cancer in the neck area. We concluded that iodine 131 total-body scan is the preferable method of follow-up, particularly when the goal of therapy is complete ablation of thyroid tissue. PMID- 2105704 TI - Mapping of pgi and gpd genes involved in C-1 assimilation in the obligate methylotroph Methylobacillus flagellatum. AB - Homologous matings with plasmids R68.45 and pULB113, and also with Hfr type donor were employed for mapping pgi and gpd genes involved in C-1 metabolism in the obligate methylotroph Methylobacillus flagellatum. A preliminary map of the late chromosomal region was constructed on the basis of these experimental results. The C-1 markers were linked to methionine and leucine auxotrophy and nalidixic acid resistance markers. The phenomenon of retrotransfer, or shuttle transfer of chromosomal markers by Inc P1 plasmids, revealed earlier, was demonstrated for M. flagellatum. PMID- 2105705 TI - Effects of carbamazepine on dopamine- and serotonin-mediated neuroendocrine responses. AB - Neuroendocrine testing was carried out in seven male volunteers before and at the end of a 10-day course of carbamazepine (up to 700 mg daily). After carbamazepine treatment, the prolactin response to intravenous administration of the serotonin precursor tryptophan (5 g) was significantly enhanced, but there was no change in basal plasma tryptophan level or in tryptophan disposition after infusion. The prolactin response to intravenous protirelin (6.25 micrograms) was unaltered. Carbamazepine treatment also produced an increase in the growth hormone response to subcutaneous administration of the dopamine agonist apomorphine hydrochloride (5 micrograms/kg). These data suggest that carbamazepine may alter brain serotonin and dopamine function in humans. Such effects could be involved in the therapeutic properties of carbamazepine in affective disorder. PMID- 2105706 TI - Fluoxetine and side effects. PMID- 2105707 TI - Ankle weighting effect on gait in able-bodied adults. AB - Energy expenditure during ambulation was measured in 10 able-bodied subjects wearing symmetrically and asymmetrically added ankle weights. When a 1.82-kg weight was added to one ankle and then both ankles, baseline oxygen consumption per unit distance (0.148 +/- 0.025 mL O2/kg/m) increased significantly by 7.4% (0.159 +/- 0.025 mL O2/kg/m) and 17.6% (0.174 +/- 0.027 mL O2/kg/m), respectively. The rate of oxygen consumption rose by 6.3% to 11.28 +/- 1.57 mL O2/kg/min and by 14.2% to 12.12 +/- 1.75 mL O2/kg/min, respectively, but only the latter increase was significant. When gait was analyzed using the same weight addition protocol, velocity, cadence, stride length, gait cycle, and double-limb support time showed no change. However, asymmetric weighting decreased single limb support time, increased the swing phase, and decreased the stance phase of gait in the weighted limb. The unweighted leg was conversely affected. Symmetric ankle weighting caused a significant increase in single-limb support time for both extremities, consistent with previous data. PMID- 2105708 TI - Influence of exercise on a heart transplant patient. AB - A treadmill training protocol was implemented to examine the effects of a 12-week exercise program on the physiologic status of a patient who had a heart transplant in 1980. The patient was tested for exercise tolerance before programming, midway through the study, and immediately upon completing endurance training. Maximal METS levels achieved were 3.2 METS, 5.6 METS, and 6.3 METS, respectively. The subject began an anaerobic program consisting of 48 exercise sessions over a three-month period. Exercise sessions were interval in nature, walking at 2.5 mph, 0% grade, three repetitions, five minutes each and increasing to 3.0 mph, 2.5% grade, two repetitions, 15 minutes each. The patient improved from Class III (METS = 3.0), where less than ordinary physical activity causes fatigue, to Class I (METS = 6.5), where ordinary physical activity can be sustained without undue fatigue. These findings suggest that selected heart transplant patients may achieve up to 85% maximum oxygen consumption and maximum heart rate which demonstrates the need for endurance training programs in this population. This form of cardiovascular conditioning has enabled the participant to engage in higher levels of activities of daily living within the community. PMID- 2105709 TI - Rehabilitation outcomes in patients with posttraumatic epilepsy. AB - This study investigated 238 consecutive admissions to an adult head trauma unit during six years. Eighty-seven patients with posttraumatic epilepsy (PTE) were identified. Rehabilitation outcome was measured by a locally developed rating scale obtained at admission and discharge for all head trauma patients. The PTE and non-PTE groups were comparable in terms of demographic and medical characteristics except for proportion of men, which was higher in the PTE group (84% vs 66%, p less than .05). Both groups demonstrated significant functional gains on all measures during the course of their hospitalization (p less than .01), although the PTE patients demonstrated lower levels of function at admission and discharge on items rated by physical, occupational, speech, and recreation therapists, and by psychologists. Furthermore, PTE patients required a higher level of nursing care on discharge (p less than .05). It appears that PTE does not impede the rehabilitation process but significantly impacts posthospital rehabilitation plans of patients with blunt head injuries. PMID- 2105710 TI - Ex vivo evaluation in normal dogs of insulin released by a bioartificial pancreas containing isolated rat islets of Langerhans. AB - In bioartificial pancreatic systems, isolated islets of Langerhans are protected against immune rejection by an artificial membrane, permeable to glucose and insulin, but not to immunoglobulins and lymphocytes. Some of these devices, referred to as vascular systems, are set up to be connected to a vascular site in the recipient, with blood circulating in contact with one side of the membrane, and the islets on the other side. Such a bioartificial pancreas, containing isolated rat islets of Langerhans, was connected to an arteriovenous shunt of a normal anesthetized dog. The aim of this experiment was to investigate the kinetics of the insulin secretory response of the system to a glucose load. Glucose was infused upstream of the system, increasing the glucose concentration inside the bioartificial pancreas from 7 to 14 mmol/l, without altering the blood glucose concentration of the dog. Insulin concentration was determined simultaneously upstream and downstream of the bioartificial pancreas. Insulin production was calculated by multiplying the difference between these values by the blood flow rate. Blood flow rate (Q) was estimated from the change in the glucose concentration produced by the glucose infusion using a mass transfer analysis derived from Fick's principle. Insulin production increased from 20 +/- 8 to 59 +/- 15 microU/100 islets/min within 15 min following the beginning of the stimulation (n = 6, p less than 0.05). Five min after the end of the stimulation, insulin production decreased from 75 +/- 13 to 50 +/- 9 microU/100 islets/min (p less than 0.05) to reach the basal level (21 +/- 3 microU/100 islets/min) 30 min after the end of the glucose stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105711 TI - Aspergillus infection of the central nervous system in patients with acquired immunodeficiency syndrome. AB - Infections of the central nervous system in patients with the acquired immunodeficiency syndrome are common. Of the many microorganisms that have been implicated, infection with Aspergillus is rare. We describe three patients with Aspergillus infection of the nervous system. Two patients had cerebral lesions due to Aspergillus flavus, and one patient had Aspergillus fumigatus infection of the spinal cord. Diagnosis of the infections was difficult, and therapy appeared to be ineffective. PMID- 2105712 TI - Retinal toxicity of recombinant tissue plasminogen activator in the rabbit. AB - We studied the dose-dependent retinal toxicity of the available commercial preparation of human recombinant tissue plasminogen activator in the normal rabbit eye. Tissue plasminogen activator was injected into the midvitreous cavity of albino rabbits in doses (per 100 microL) of 25, 50, 75, and 100 micrograms. Control eyes received 100 microL of balanced salt solution or tissue plasminogen activator vehicle. No evidence of a retinal toxic reaction was seen in eyes receiving 25 micrograms of tissue plasminogen activator. One of four eyes injected with 50 micrograms showed loss of photoreceptor cells by light microscopy. Severe retinal damage was seen by ophthalmoscopy, electroretinography, and light microscopy in three of four eyes receiving 75 micrograms of tissue plasminogen activator and in all eyes treated with 100 micrograms of tissue plasminogen activator or equivalent vehicle. These results suggest that the commercial recombinant tissue plasminogen activator formulation has a narrow margin of safety in nonvitrectomized eyes and that a component of the vehicle is the toxic factor. PMID- 2105713 TI - Rebleeding in experimental traumatic hyphema treated with intraocular tissue plasminogen activator. AB - Tissue plasminogen activator has recently been shown to enhance the clearance of experimental nontraumatic hyphema in animals. However, hyphema in human eyes usually results from ocular trauma, and rebleeding is a serious complication. Hemorrhage is also a potential complication of fibrinolytic therapy. We assessed the incidence of rebleeding in an animal model of surgically induced traumatic hyphema after intracameral injection of tissue plasminogen activator (25 micrograms) or physiological saline. Eight eyes were each treated with tissue plasminogen activator or physiological saline at 10 minutes, 24 hours, 48 hours, or 72 hours after injury. Controls were 8 eyes with hyphema but no intracameral injection. No eyes treated with physiological saline (total, 32 eyes) or control eyes rebled. In contrast, the incidence of rebleeding from the injury site in eyes treated with tissue plasminogen activator was 88% (7/8) at 10 minutes, 75% (6/8) at 24 hours, 50% (4/8) at 48 hours, and 0% (0/8) at 72 hours after injury. Treatment of traumatic hyphema with tissue plasminogen activator prior to healing of damaged vascular endothelium may contribute to rebleeding. PMID- 2105714 TI - The mechanism of the reaction between human plasminogen-activator inhibitor 1 and tissue plasminogen activator. AB - The structural events taking place during the reaction between PAI-1 (plasminogen activator inhibitor 1) and the plasminogen activators sc-tPA (single-chain tissue plasminogen activator) and tc-tPA (two-chain tissue plasminogen activator) were studied. Complexes were formed by mixing sc-tPA or tc-tPA with PAI-1 in slight excess (on an activity basis). The complexes were purified from excess PAI-1 by affinity chromatography on fibrin-Sepharose. Examination of the purified complexes by SDS/polyacrylamide-gel electrophoresis (SDS/PAGE) and N-terminal amino acid sequence analysis demonstrated that a stoichiometric 1:1 complex is formed between PAI-1 and both forms of tPA. Data obtained from both complexes revealed the amino acid sequences of the parent molecules and, in addition, a new sequence: Met-Ala-Pro-Glu-Glu-. This sequence is found in the C-terminal portion of the intact PAI-1 molecule and thus locates the reactive centre of PAI-1 to Arg346-Met347. The proteolytic activity of sc-tPA is demonstrated by its capacity to cleave the 'bait' peptide bond in PAI-1. The complexes were inactive and dissociated slowly at physiological pH and ionic strength, but rapidly in aq. NH3 (0.1 mol/l). Amidolytic tPA activity was generated on dissociation of the complexes, corresponding to 0.4 mol of tPA/mol of complex. SDS/PAGE of the dissociated complexes indicated a small decrease in the molecular mass of PAI-1, in agreement with proteolytic cleavage of the 'bait' peptide bond during complex formation. PMID- 2105715 TI - Brefeldin A arrests the intracellular transport of viral envelope proteins in primary cultured rat hepatocytes and HepG2 cells. AB - We have studied the effect of brefeldin A (BFA) on the intracellular transport of the envelope proteins of vesicular stomatitis virus (VSV) and sindbis virus in primary cultured rat hepatocytes. BFA (2.5 micrograms/ml) inhibited not only the secretion of plasma proteins into the medium, but also the assembly of both G protein of VSV and E1 and E2 proteins (envelope proteins) of sindbis virus into respective virions. Concomitantly, both the acquisition of endo-beta-N acetylglucosaminidase H resistance by the G protein and the proteolytic conversion of PE2 to E2 were found to be inhibited in the BFA-treated cells, suggesting that the intracellular transport of the envelope proteins was arrested in the endoplasmic reticulum. Such inhibitory effects of the drug were variable depending upon the culture conditions of the hepatocytes. In the 1-day-cultured cells, even in the presence of the drug, newly synthesized envelope proteins were assembled into the virions after a 3 h chase period, at the same time as secretion of plasma proteins into the medium resumes. In contrast, in 4-day cultured hepatocytes, BFA continuously blocked the entry of the envelope proteins into the virions and the release of plasma proteins into the medium for at least 5 h. BFA also completely inhibited the exocytotic pathway in HepG2 cells. These results indicate that the duration time of the effect of BFA is different from one cell to another and may change depending upon the culture conditions of the cells. PMID- 2105716 TI - Isolation of insecticide resistance-related forms of cytochrome P-450 from Drosophila melanogaster. AB - Significant purification of the ubiquitous cytochrome P-450-A and the strain specific P-450-B from Drosophila melanogaster has been achieved by sequential chromatography on octylamino-agarose, DEAE-cellulose and hydroxyapatite. Preparations of P-450-A (specific contents of 7-9 nmol/mg) were homogeneous as determined by SDS/polyacrylamide-gel electrophoresis (PAGE) analysis. Preparations enriched for P-450-B (specific contents of 4-7 nmol/mg) contained significant amounts of P-450-A but were essentially free of other proteins as judged by SDS/PAGE. Partial reconstitution of 7-ethoxycoumarin de-ethylase activity was achieved using rabbit NADPH: cytochrome P450 reductase and purified preparations containing P450-B. PMID- 2105717 TI - Replacement of isoleucine-397 by threonine in the clotting proteinase factor IXa (Los Angeles and Long Beach variants) affects macromolecular catalysis but not L tosylarginine methyl ester hydrolysis. Lack of correlation between the ox brain prothrombin time and the mutation site in the variant proteins. AB - Previously, from the plasma of unrelated haemophilia-B patients, we isolated two non-functional Factor IX variants, namely Los Angeles (IXLA) and Long Beach (IXLB). Both variants could be cleaved to yield Factor IXa-like molecules, but were defective in catalysing the cleavage of Factor X (macromolecular substrate) and in binding to antithrombin III (macromolecular inhibitor). In the present study we have identified the mutation of IXLA by amplifying the exons (including flanking regions) as well as the 5' end of the gene by polymerase-chain-reaction (PCR) method and sequencing the amplified DNA by the dideoxy chain-termination method. Comparison of the normal IX and IXLA sequences revealed only one base substitution (T----C) in exon VIII of IXLA, with a predicted replacement of Ile 397 to Thr in the mature protein. This mutation is the same as found recently for IXLB. The observation that IXLB and IXLA have the same mutation is an unexpected finding, since, on the basis of their ox brain prothrombin time (PT, a test that measures the ability of the variant Factor IX molecules to inhibit the activation of Factor X by Factor VIIa-tissue factor complex), these variants have been classified into two different groups and were thought to be genetically different. Our observation thus suggests that the ox brain PT does not reflect the locus of mutation in the coding region of the variant molecules. However, our analysis suggests that the ox brain PT is related to Factor IX antigen concentration in the patient's plasma. Importantly, although the mutation in IXLA or IXLB protein is in the catalytic domain, purified IXaLA and IXaLB hydrolyse L tosylarginine methyl ester at rates very similar to that of normal IXa. These data, in conjunction with our recent data on Factor IXBm Lake Elsinore (Ala-390-- -Val mutant), strengthen a conclusion that the peptide region containing residues 390-397 of normal Factor IXa plays an essential role in macromolecular substrate catalysis and inhibitor binding. However, the two mutations noted thus far in this region do not distort S1 binding site in the Factor IXa enzyme. PMID- 2105718 TI - Studies on the hyperplasia ('regeneration') of the rat liver following partial hepatectomy. Changes in lipid peroxidation and general biochemical aspects. AB - Using the experimental model of partial hepatectomy in the rat, we have examined the relationship between cell division and lipid peroxidation activity. In rats entrained to a regime of 12 h light/12 h dark and with a fixed 8 h feeding period in the dark phase, partial hepatectomy is followed by a rapid regeneration of liver mass with cycles of synchronized cell division at 24 h intervals. The latter phenomenon is indicated in this study by pulses of thymidine kinase activity having maxima at 24 h, 48 h and 72 h after partial hepatectomy. Microsomes prepared from regenerating livers show changes in lipid peroxidation activity (induced by NADPH/ADP/iron or by ascorbate/iron), which is significantly decreased relative to that in microsomes from sham-operated controls, again at 24 h, 48 h and 72 h after the operation. This phenomenon has been investigated with regard to possible underlying changes in the content of microsomal fatty acids, the microsomal enzymes NADPH:cytochrome c reductase and cytochrome P-450, and the physiological microsomal antioxidant alpha-tocopherol. The cycles of decreased lipid peroxidation activity are apparently due, at least in part, to changes in microsomal alpha-tocopherol content that are closely associated in time with thymidine kinase activity. PMID- 2105719 TI - Secretion of Bacillus subtilis levansucrase. Fe(III) could act as a cofactor in an efficient coupling of the folding and translocation processes. AB - The refolding of levansucrase denatured by urea was studied as a possible model for the second step of the secretion pathway of this protein. The folding unfolding transition was monitored by measuring intrinsic fluorescence and resistance to proteolysis. Both methods provided the same estimation for the unfolding free energy of levansucrase, delta GD, which was 30.1 +/- 1.7 kJ.mol-1 (7.2 +/- 0.4 kcal.mol-1) at pH 7 in 0.1 M-potassium phosphate buffer. The rate of refolding was greatly enhanced by Fe3+, whereas the Fe3+ chelator EDTA prevented correct refolding. Fe3+ allowed the protein to reach its folded form in medium in which the dielectric constant had been lowered by ethanol. The efficiency in vivo of the export of levansucrase bearing an amino acid modification which blocks the second step of the translocation pathway was greatly increased by high concentrations of Fe3+ in the culture medium. Assuming that the protein folding governs the second step of the secretion process of levansucrase, we discuss from an irreversible thermodynamic point of view the possible role of Fe3+ in the efficient coupling of the two events. PMID- 2105720 TI - Adrenergic and calcium-mediated subcellular redistribution of protein kinase C in primary neuronal cultures. AB - Incubation of primary neuronal cultures prepared from the brains of neonatal rats with 50 microM epinephrine resulted in the transient redistribution of protein kinase C from the cytosol to the particulate fraction. This effect occurred after 1 and 5 min of incubation and resulted in a decrease in cytosolic protein kinase C activity with a corresponding increase in particulate protein kinase C of approximately 30% and 15%, respectively. The epinephrine-stimulated translocation of protein kinase C was blocked by 1 microM prazosin indicating the involvement of alpha 1-adrenergic receptors. Further, inclusion of 0.1 microM Ca2+ in the homogenization buffer was found to significantly enhance the binding of protein kinase C to cellular membranes prepared from neuronal cultures. These results indicate that alpha 1-adrenergic receptors in neuronal brain cell cultures are linked to the activation of protein kinase C and that the mobilization of Ca2+ may enhance this effect. PMID- 2105721 TI - Hydrogen peroxide: a potent activator of dioxygenase activity of soybean lipoxygenase. AB - Hydrogen peroxide, an ubiquitous biologically occurring peroxide, was found to stimulate the dioxygenase activity of soybean lipoxygenase at the physiologically attainable concentration. The increase in enzyme specific activity was directly proportional to hydrogen peroxide concentration up to 0.5 nM. A decrease in the stimulation of dioxygenase activity was observed at higher concentrations. At low enzyme concentration up to 28-fold stimulation was noted when the formation of lipid hydroperoxide was monitored spectrophotometrically. The stimulation was further confirmed by increased oxygen uptake. It is proposed that the mechanism for in vivo activation involves hydrogen peroxide. PMID- 2105722 TI - Pepsin, an aspartic protease, converts porcine big endothelin to 21-residue endothelin. AB - Porcine big endothelin (big ET-39) at 1 nM, a concentration with no influence on contractile activity in isolated rat aorta, induced a slow-onset and sustained contraction by the pre-incubation with pepsin. When the incubation mixture of big ET-39 with pepsin was analyzed by high-performance liquid chromatography on an octadecyl silica column, two major products of pepsin hydrolysis were obtained; their amino acid sequences were identical with those of 21-residue endothelin (ET 21) and a C-terminal peptide of big ET-39, big ET (22-39), respectively. On the other hand, no degradation of ET-21 was observed by pepsin treatment. These results indicate that pepsin specifically cleaves a Trp21-Val22 bond in the big ET-39 molecule, producing ET-21 and big ET (22-39). Thus, the possibility that pepsin-like aspartic protease may participate in the conversion of big ET-39 to ET-21 in vivo warrants further attention. PMID- 2105723 TI - Presence in invertebrate genomes of sequences characterized by the repetition of the triplet CCPurine. AB - In Drosophila melanogaster (Dm), polypeptidic domains have been found in different morphogenetic genes. Two types of them are characterized by the repetition of nucleotidic triplets: the M repeat (CAX) and the paired repeat (CAXCCX). In this paper we described a third type of repeat isolated from the genome of a Polychaete annelid: Owenia fusiformis. This repeat is characterized by the repetition of the triplet CCPurine. Phylogenetic studies showed the presence of this repeat in all the invertebrate genomes tested (eight copies in Dm genome) while we failed to detect it in vertebrate genomes. PMID- 2105724 TI - Molecular cloning of smg p21B and identification of smg p21 purified from bovine brain and human platelets as smg p21B. AB - We have previously purified smg p21 from bovine brain membranes and isolated its cDNA from a bovine brain cDNA library. In the present studies, we have performed extensive screening of the bovine brain cDNA library with the cloned smg p21 cDNA as a probe and isolated another cDNA encoding a protein highly homologous to smg p21. The proteins encoded by the previously and newly isolated cDNAs are designated as smg p21A and -B, respectively. Since the partial amino acid sequences determined previously from the smg p21 purified from bovine brain were identical with the common amino acid sequences between smg p21A and -B, we have further sequenced smg p21 and identified it as smg p21B. We have also further sequenced the smg p21 purified from human platelet membranes and identified it as smg p21B. Amino acid sequence analysis indicates that smg p21A is identical with the rap1A and Krev-1 proteins and smg p21B is identical with the rap1B protein. PMID- 2105725 TI - Structural studies of rat cathepsin E: amino-terminal structure and carbohydrate units of mature enzyme. AB - The amino-terminal structure of rat gastric cathepsin E was identified and compared with the corresponding regions of human procathepsin E and other aspartic proteinases. The alignment revealed that cathepsin E has the most extended amino-terminal structure in aspartic proteinases, thus suggesting that the activation peptide (propeptide) of the human enzyme is 39-residues long. Analysis of oligosaccharide units suggested that rat cathepsin E possesses one N linked carbohydrate unit, probably of the high mannose type. No evidence was obtained for the presence of O-linked sugars in rat cathepsin E. PMID- 2105726 TI - Temporally defined induction of c-fos in the rat pineal. AB - In the rat pineal gland c-fos is transiently and markedly induced after the onset of darkness. The induction is abolished following removal of the superior cervical ganglion and reproduced in ganglionectomized animals by treatment with the adrenergic agonist isoproterenol. These findings show for the first time that induction of c-fos forms an integral part of physiological changes in cellular activity. Expression of the c-fos gene may be functionally linked to the nocturnal changes in pineal indole metabolism. PMID- 2105727 TI - Activation of promutagenic chemicals by Streptomyces griseus containing cytochrome P-450soy. AB - Streptomyces griseus cells containing cytochrome P-450soy oxidize a diverse array of xenobiotic compounds. This metabolic capability was exploited for activation of promutagenic chemicals such as polycyclic aromatic hydrocarbons, aromatic amines and small aliphatics in a modified Salmonella/Ames plate incorporation assay using tester strains TA98 and TA1538. In this assay promutagens such as 3,3'-dimethylbenzidine, 3,3'-dimethoxybenzidine, benzidine, 2 acetylaminofluorene, 2-aminoanthracene, 2,4-diaminotoluene, 4-aminobiphenyl, benzo(a)pyrene, chloropicrin and N-nitrosodimethylamine were oxidized to mutagenic metabolites by S. griseus intact cells which mutated Salmonella tester strains (TA98 and TA1538). S. griseus failed to activate 7,12 dimethylbenzanthracene and 4-chloro-2-nitroaniline. In parallel tests performed with rat liver homogenate (S9), N-nitrosodimethylamine was not activated. PMID- 2105728 TI - Characterization and amino-terminal sequence of apolipoprotein AI from plasma high density lipoproteins in the preruminant calf, Bos spp. AB - The major apolipoprotein of calf plasma high-density lipoproteins, apo-AI, has been isolated and characterized. Apolipoprotein AI (apo-AI) was separated from the protein moiety of high-density lipoproteins (d 1.090-1.180 g/ml) by preparative electrophoresis in SDS-polyacrylamide gels followed by electrophoretic elution. Purified calf apo-AI had an Mr of approx. 27,000-28,000 in SDS-polyacrylamide gels, resembling human apo-AI. The amino acid composition of calf apo-AI displayed an overall similarity to that of its human and other mammalian counterparts (baboon, dog, badger, rabbit, rat and mouse), but differed in having higher proportions of glutamic acid, alanine and isoleucine. Amino terminal amino acid sequence analysis up to the 47th residue showed close homology between calf apo-AI and those of the mammals with which it was compared. However, residues 2, 7, 20 and 22 in calf AI (i.e. aspartic acid, serine, glutamic acid and isoleucine, respectively) were substituted by glutamic acid, proline or glutamine, aspartic acid, and valine or leucine respectively, in the other mammals. PMID- 2105729 TI - Intramolecular long-range electron transfer in the hemerythrin monomer: a pulse radiolysis study. AB - The single sulfhydryl group (Cys-50) of the methemerythrin from Phascolosoma gouldii reacts with 5,5'dithiobis(2-nitrobenzoic acid) to form a mixed disulfide. The pulse radiolytically generated formate radical reduces this mixed disulfide to its radical anion. In turn, the disulfide radical anion reduces the protein two-iron center over a nominal distance of 13 A. The rate constant for this intramolecular electron transfer is approximately 15 s-1 at room temperature, pH 7. Between the two redox centers there is an equilibrium driving force of 0.78 V, measured by differential pulsed polarography. PMID- 2105731 TI - Modulation of mediator release from human basophils and pulmonary mast cells and macrophages by auranofin. AB - Auranofin, a new orally absorbable gold compound, inhibits IgE-(anti-IgE) and non IgE-mediated (f-met-peptide and the Ca2+ ionophore A23187) histamine release from human basophils. Auranofin inhibits the release of histamine induced by phorbol myristate (TPA) and bryostatin 1 both in the presence and absence of extracellular Ca2+. Increasing the Ca2+ concentrations in the extracellular medium does not reduce the inhibitory effect of auranofin on anti-IgE- or A23187 induced secretion. Auranofin inhibits the de novo synthesis of sulfidopeptide leukotriene C4 (LTC4) induced by anti-IgE from basophils and mast cells purified from human lung. However, in both systems auranofin has a significantly greater inhibitory effect on LTC4 release than on histamine secretion. Finally, auranofin induces a concentration-dependent inhibition of A23187-induced leukotrine B4 (LTB4) release from purified human lung macrophages. These data suggest that auranofin modulates the release of preformed (histamine) and de novo synthesized (LTC4 and LTB4) chemical mediators from human inflammatory cells isolated from peripheral blood and human lung tissues. PMID- 2105730 TI - Effect of enzyme induction on Sandimmun (cyclosporin A) biotransformation and hepatotoxicity in cultured rat hepatocytes and in vivo. AB - This study was designed to examine the relationship between the extent of Sandimmun (cyclosporin A, SIM) metabolism and SIM-induced hepatotoxicity both in vivo and in primary cultures of rat hepatocytes. Firstly, SIM (50 mg/kg p.o.) was administered daily to male Wistar rats for 10 days with or without co administration of Aroclor 1254. SIM-induced hepatotoxicity appeared after 4 days of treatment and was enhanced after 10 administrations of SIM. Total plasma proteins were decreased and hyperbilirubinemia as well as increased levels of plasma bile salts were prominent. Aroclor 1254 stimulated total hepatic cytochrome P-450 3.7-fold, and markedly increased the rate of SIM metabolism and plasma elimination as determined by both HPLC and RIA techniques. However, this induction did not change the degree of SIM-induced hepatotoxicity. Secondly, short-term cultures of hepatocytes obtained from normal rats and from rats pretreated with either Aroclor 1254 or dexamethasone, a specific inducer of the cytochrome P-450 III gene family responsible for the formation of the primary SIM metabolites M1, M17 and M21, were incubated with various concentrations of SIM for up to 17 hr. At 1 microM SIM, both inducers greatly increased the rate of SIM metabolism in vitro, producing, however, different metabolite patterns. In the hepatocyte cultures, SIM inhibited the incorporation of amino acids into proteins. In addition, a small fraction of [3H]-labeled SIM was covalently bound to hepatocellular macromolecules. Although the fraction of covalently bound SIM was markedly increased in cells from dexamethasone-treated rats, the degree of inhibition of hepatocellular protein synthesis was not changed in cells from induced rats. In contrast to SIM-induced nephrotoxicity, these results suggest that increased rates of SIM biotransformation by inducers of drug metabolism are not associated with an attenuation of hepatotoxicity both in vivo and in vitro. PMID- 2105732 TI - NAD(P)H: quinone oxidoreductase (DT-diaphorase) in chick embryo liver. Comparison to activity in rat and guinea pig liver and differences in co-induction with 7 ethoxyresorufin deethylase by 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - NAD(P)H:quinone oxidoreductase (EC 1.6.99.2; DT-diaphorase) was present in the liver of 18- and 19-day-old chick embryos as assayed both by reduction of resorufin and by the more traditional assay, reduction of 2,6 dichlorophenolindophenol (DCPIP). Both reductions had the classic characteristics of DT-diaphorase: they were equally supported by NADPH and NADH and almost entirely inhibited by dicumarol. Chick embryo liver DT-diaphorase was entirely cytosolic. It was undetectable in the microsomal and mitochondrial fractions. Chick embryo liver cytosol and mitochondrial fractions contained an enzyme oxidizer of resorufin but not of DCPIP. The Km for NADPH for resorufin reductase was an order of magnitude higher in chick embryo than in rat or guinea pig cytosol (1 mM vs 0.1 mM). Resorufin reductase activity was higher for chick embryo than for rat or guinea pig cytosols: Vmax (nmol resorufin reduced per mg cytosolic protein per min +/- SEM) 355 +/- 28 for chick embryo, 159 +/- 10 for guinea pig and 68 +/- 28 for rat. The Vmax for DCPIP reduction was also twice as high in chick embryo as rat liver cytosol. In the chick embryo, 7 days after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 6.4 micrograms/kg egg (1 nmol/egg) mortality was increased 2.4-fold, hepatic DT-diaphorase 1.3 fold, and 7-ethoxyresorufin deethylase (7-EROD) 72-fold over control levels. At 32 micrograms/kg, mortality was increased 4.2-fold, DT-diaphorase 2.3-fold and 7 EROD 100-fold. In the guinea pig, 5 days after treatment with TCDD at 10 micrograms/kg, TCDD toxicity was also evident (loss of body weight and thymus weight); there was no change in DT-diaphorase as measured by resorufin reduction, confirming by a different assay the observation of Beatty and Neal (Biochem Pharmacol 27: 505-510, 1978) that TCDD does not induce DT-diaphorase in guinea pig liver, and 7-EROD was increased 8-fold. In contrast, in the rat, 7 days after exposure to TCDD at 10 micrograms/kg, there was no evidence of toxicity, DT diaphorase was increased close to 7-fold and 7-EROD, 100-fold. The results demonstrate that avian liver contains DT-diaphorase and show that the extent to which DT-diaphorase is part of the pleiotypic response of the liver to an Ah (aryl hydrocarbon) receptor ligand is species dependent. They also suggest that DT-diaphorase induction and TCDD toxicity may be inversely related. The possibility that DT-diaphorase protects against TCDD toxicity and participates in species differences in sensitivity to TCDD toxicity warrants further investigation. PMID- 2105733 TI - Ponalrestat: a potent and specific inhibitor of aldose reductase. AB - Many of the complications of diabetes appear to be closely linked to increased conversion of tissue glucose to sorbitol which is catalysed by aldose reductase (aldehyde reductase 2, ALR2). Inhibition of ALR2 could, therefore, lead to a reduction in the development of diabetic complications. Ponalrestat ["Statil" (a trademark, the property of Imperical Chemical Industries PLC), "Prodiax" (a trademark, the property of Merck, Sharp and Dohme), ICI 128436, MK538] inhibits ALR2 from a number of sources. Until now, the mechanism of this inhibition has not been fully elucidated. In this paper, we present a detailed mechanism for inhibition of bovine lens ALR2 by ponalrestat. Treatment of humans with some ALR2 inhibitors leads to side-effects, some of which may result from interactions with other enzymes. Aldehyde reductase (ALR1) is probably the most closely related enzyme to ALR2. Inhibition of ALR1 from bovine kidney was, therefore, investigated in order to assess the specificity of ponalrestat. The values of Ki and Kies (apparent dissociation constants for inhibitor from enzyme-inhibitor and enzyme-inhibitor-substrate complexes, respectively) for the interactions of ponalrestat with ALR1 and ALR2 has been calculated by non-linear fitting of kinetic data. These values indicate that ponalrestat does not compete with binding of glucose of NADPH to ALR2, nor with binding of glucuronate or NADPH to ALR1. Lack of competition and the structural dissimilarity of substrates and inhibitor make it unlikely that ponalrestat will utilize substrate binding sites on other enzymes, and so produce undesirable side-effects via such a mechanism. Ponalrestat is a potent inhibitor (Ki = Kies = 7.7 nM) of ALR2 and follows a pure noncompetitive mechanism with respect to glucose. Efficacy, therefore, will not be decreased by development of hyperglycaemia. The compound is a mixed noncompetitive inhibitor of ALR1 when glucuronate is varied. The values of Ki and Kies are 60 microM and 3 microM, respectively, so that inhibition tends towards uncompetitive. The selectivity of ponalrestat in favour of ALR2, therefore, lies in the range 390 to 7,800-fold, being higher at lower concentrations of glucuronate. The high selectivity of ponalrestat in favour of ALR2 rather than ALR1 suggests that the compound is unlikely to inhibit other enzymes which have less homology with ALR2. PMID- 2105734 TI - Effect of phenobarbital induction, charcoal treatment and storage on the spectral binding characteristics and NADPH-cytochrome P-450 reductase activity of hepatic microsomes. PMID- 2105735 TI - 6-Hydroxydopamine lesions of the olfactory tubercle do not alter (+)-amphetamine conditioned place preference. AB - Rats received bilateral infusions of 6-hydroxydopamine into the olfactory tubercle, resulting in a substantial (89%) local depletion of dopamine. This treatment did not significantly alter conditioned place preference produced by (+)-amphetamine, suggesting that the mesolimbic dopaminergic projection to olfactory tubercle does not mediate the rewarding effects of (+)-amphetamine in rats. PMID- 2105736 TI - The evolution of an acute care hospital unit to a DRG-exempt rehabilitation unit. A preliminary communication. AB - The Health Care Financing Administration's decision to adopt a prospective based payment system has caused many institutions to implement new policies and practices. A recent area of interest for many hospitals has been the creation of diagnosis-related group (DRG) exempt units to maximize reimbursement practices. We analyzed changes which occurred when an eight bed acute care stroke unit (SU) was converted to a DRG exempt eight bed rehabilitation unit (RU). The time period involved was 1 1/2 months before and 1 1/2 months after the transition occurred. Analysis of data from the pre- and posttransition periods revealed that: (1) length of stay increased significantly from 11.7 to 15.3 days (P less than 0.001); (2) functional independence measure (FIM) score improvement was significantly greater (P less than 0.05) for RU patients (0.84/day) than for SU patients (0.39/day); (3) disposition to home v other facilities increased significantly from 50 to 81% (P less than 0.05); (4) the overall occupancy increased from 94 to 100% and all beds were filled with rehabilitation patients; (5) the proportion of patients with Medicare as their primary insurer was comparable before (64%) and after (67%) unit conversion; (6) gross income from rehabilitation patients increased by 43%. Indirect savings via reduction of acute hospital length of stay for Medicare patients increased total income from operation of this unit. We conclude that patients on the RU stayed longer, had greater daily improvements in functional status, and were more likely to be discharged to home. This appears to be due to a more efficient use of rehabilitation beds and a concomitant overall improvement in reimbursement to the hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105737 TI - The effect of cholesterol on the morphology and reactivity of the mixture of lipids used in syphilis serology. AB - The effect of increasing amounts of cholesterol on the morphology of the liposomes constituting the VDRL-antigen was studied. The morphological parameters examined were the shape of the lipoidal particles and especially the number of lamellae on each particle in the various mixtures of lipids studied. Cholesterol in the presence of cardiolipin and lecithin is observed as rhomboid crystals, indicating that the majority of the cholesterol is located exterior to the lamellar membranes of lecithin and cardiolipin. It is shown that the effect of cholesterol is to reduce the number of individual lamellae per liposome, mainly by mechanically dispersing the cardiolipin and lecithin on the surface of the cholesterol crystals. It is suggested that cholesterol has no effect on the structure of the epitopes which react with antibodies in sera from patients with syphilis, but that, as a result of the mechanical dispersion of cardiolipin and lecithin, it creates liposomes with more accessible epitopes. PMID- 2105738 TI - The promise of transdermal drug delivery. PMID- 2105739 TI - Fluorescence analysis of the size of a binding pocket of a peptide receptor at natural abundance. AB - We have studied the topography of interaction of a family of fluorescent formyl peptides containing four (CHO-Met-Leu-Phe-Lys-fluorescein), five (CHO-Met-Leu-Phe Phe-Lys- fluorescein), and six (CHO-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein and CHO Met-Leu-Phe-Phe-Phe-Lys- fluorescein) amino acids with their receptor using spectroscopic methods adapted to small sample volumes. Only the fluorescent peptides containing four and five amino acids were quenched upon binding to the receptor, indicating physical contact of the chromophore with the receptor. In contrast, only the hexapeptides were accessible to antibodies to fluorescein. Taken together, these results suggest that the carboxy terminus of the tetrapeptide or the pentapeptide is protected in the receptor binding pocket while the fluorescein on the carboxy terminus of either hexapeptide is exposed and recognized by the antibody to fluorescein. These results indicate that the binding pocket accommodates at least five but no more than six amino acids. PMID- 2105740 TI - High-resolution structure of an HIV zinc fingerlike domain via a new NMR-based distance geometry approach. AB - A new method is described for determining molecular structures from NMR data. The approach utilizes 2D NOESY back-calculations to generate simulated spectra for structures obtained from distance geometry (DG) computations. Comparison of experimental and back-calculated spectra, including analysis of cross-peak buildup and auto-peak decay with increasing mixing time, provides a quantitative measure of the consistence between the experimental data and generated structures and allows for use of tighter interproton distance constraints. For the first time, the "goodness" of the generated structures is evaluated on the basis of their consistence with the actual experimental data rather than on the basis of consistence with other generated structures. This method is applied to the structure determination of an 18-residue peptide with an amino acid sequence comprising the first zinc fingerlike domain from the gag protein p55 of HIV. This is the first structure determination to atomic resolution for a retroviral zinc fingerlike complex. The peptide [Zn(p55F1)] exhibits a novel folding pattern that includes type I and type II NH-S tight turns and is stabilized both by coordination of the three Cys and one His residues to zinc and by extensive internal hydrogen bonding. The backbone folding is significantly different from that of a "classical" DNA-binding zinc finger. Residues C(1)-F(2)-N(3)-C(4)-G(5) K(6) fold in a manner virtually identical with the folding observed by X-ray crystallography for related residues in the iron domain of rubredoxin; superposition of all main-chain and Cys side-chain atoms of residues C(1)-K(6) of Zn(p55F1) onto residues C(6)-Y(11) and C(39)-V(44) of rubredoxin gives RMSDs of 0.46 and 0.35 A, respectively. The side chains of conservatively substituted Phe and Ile residues implicated in genomic RNA recognition form a hydrophobic patch on the peptide surface. PMID- 2105741 TI - A protein isolated from Brucella abortus is a Cu-Zn superoxide dismutase. AB - Brucella abortus contains a protein that elicits an antigenic response in cattle previously exposed to the organism. The amino acid sequence of the recombinant form of this antigenic protein was determined by gas-phase sequencing of the pyridylethylated protein and its peptides obtained by digestion with cyanogen bromide (CNBr), clostripain, and Staphylococcus aureus V8 protease. The Brucella protein demonstrated 53.6% identity with the Cu-Zn superoxide dismutase (SOD) from Photobacterium leiognathi. Residues essential for metal coordination and enzymatic activity and cysteines required for the formation of the intrasubunit disulfide bridge of Cu-Zn SOD were conserved in the Brucella protein. also exhibited SOD activity that was inhibited by cyanide, which is characteristic of a Cu-Zn SOD. Brucella abortus Cu-Zn SOD is the second prokaryotic Cu-Zn SOD to be sequenced, and the fifth found in prokaryotes. The high degree of conservation between Photobacterium and Brucella Cu-Zn SOD supports the hypothesis of a separately evolved prokaryotic and eukaryotic Cu-Zn SOD gene. PMID- 2105742 TI - Monofunctional chorismate mutase from Bacillus subtilis: purification of the protein, molecular cloning of the gene, and overexpression of the gene product in Escherichia coli. AB - The monofunctional chorismate mutase from Bacillus subtilis has been purified 2200-fold to homogeneity. The enzyme is a homodimer of subunit Mr = 14,500 and is the smallest natural chorismate mutase that has been characterized. The purified enzyme follows Michaelis-Menten kinetics with a Km of 100 microM and a kcat of 50 s-1, carries no other associated enzymic activities, and is unaffected by any of the aromatic amino acids. The N-terminal amino acid sequence of the protein has been determined, and this information has been used to construct a precise oligonucleotide probe for the gene by means of in vitro DNA amplification from total chromosomal DNA by the polymerase chain reaction. The cloned aroH gene encodes a protein of 127 amino acid residues and is expressed in Escherichia coli. The cloned gene product is indistinguishable from that purified from Bacillus. The aroH coding region was directly subcloned into a phagemid expression vector by means of the polymerase chain reaction. The resulting construct, with the aroH gene positioned behind efficient transcription and translation initiation sequences of E. coli, results in the production of the monofunctional mutase at levels of 30-35% of the soluble cell protein in E. coli transformants. Chorismate mutases comprise a set of functionally related proteins that show little sequence similarity to each other. This diversity stands in contrast to other chorismate-utilizing enzymes. PMID- 2105744 TI - Spectroscopic characterization of the light-harvesting complex of Rhodospirillum rubrum and its structural subunit. AB - The spectroscopic properties of the light-harvesting complex of Rhodospirillum rubrum, B873, and a detergent-isolated subunit form, B820, are presented. Absorption and circular dichroism spectra suggest excitonically interacting bacteriochlorophyll alpha (BChl alpha) molecules give B820 its unique spectroscopic properties. Resonance Raman results indicate that BCHl alpha is 5 coordinate in both B820 and B873 but that the interactions with the BChl C2 acetyl in B820 and B873 are different. The reactivity of BChl alpha in B820 in light and oxygen, or NaBH4, suggests that it is exposed to detergent and the aqueous environment. Excited-state lifetimes of the completely dissociated 777-nm absorbing form [1.98 ns in 4.5% octyl glucoside (OG)], the intermediate subunit B820 (0.72 ns in 0.8% OG), and the in vivo like reassociated B873 (0.39 ns in 0.3% OG) were measured by single-photon counting. The fluorescence decays were exponential when emission was detected at wavelengths longer than 864 nm. An in vivo like B873 complex, as judged by its spectroscopic properties, can be formed from B820 without the presence of a reaction center. PMID- 2105743 TI - Kinetic properties of the K+/H+ antiport of heart mitochondria. AB - The fluorescence of 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) has been used to follow a K(+)-dependent alkaline shift in the matrix pH (pHi) of isolated heart mitochondria. The K(+)-dependent pHi change has properties consistent with an inward exchange of K+ for matrix H+ on the K+/H+ antiport of the mitochondrion. The reaction is activated by depletion of matrix Mg2+ with A23187 and by an alkaline external pH (pHo) and hypotonic conditions. The exchange is inhibited by quinine, dicyclohexylcarbodiimide, and exogenous Mg2+, but not by Li+. The rate of K+/H+ antiport measured in this way increases with increasing pHo to a maximum near pHo 9. The rate is a hyperbolic function of [K+] at pHo values above 8.3 with an apparent Km of 30 mM at pHo 8.4 and 14 mM at pHo 8.8. External H+ acts as a mixed-type inhibitor of the K+/H+ antiport under these conditions with a Ki equivalent to pHo 8.6-8.8. When pHo is kept constant, the reaction is relatively insensitive to matrix pH (pHi) in the range from 7.0 to 7.5. Above this pHi, the K(+)-dependent H+ extrusion shows a hyperbolic dependence on [H+]i with an apparent Km equivalent to pHi 8.1. The activated antiport shows an affinity sequence of Li+ greater than K+ = Rb+ greater than Cs+. The inward antiport of K+ is inhibited noncompetitively by NH4+ and is also sensitive to benzamil and to 5-N-substituted amiloride analogues with I50 values near 20 microM. Both NH4+ and the amiloride analogues increase pHi at constant pHo and appear to be concentrated in the matrix under these conditions. PMID- 2105745 TI - Drug binding by branched DNA molecules: analysis by chemical footprinting of intercalation into an immobile junction. AB - Branched DNA structures interact with drugs differently from unbranched control duplexes of similar sequence. A specific interaction between the reagent (methidiumpropyl-EDTA).Fe(II) [MPE.Fe(II)] and a branched DNA molecule formed from 16-mer oligonucleotide strands has been reported [Guo, Q., Seeman, N. C., & Kallenbach, N. R. (1989) Biochemistry 28, 2355-2359]. The structure of the branched molecule is thought to be made up of two double-helical stacking domains with an overall twofold symmetry across the branch site. The MPE-Fe(II) interaction occurs predominantly at or adjacent to the branch site and is eliminated by a second intercalator, propidium iodide. Further studies on the nature and properties of this site are presented here. Comparison of the patterns of scission of linear duplex and branched tetramer by EDTA.Fe(II), MPE.Fe(II), and Cu(I)-(o-phenanthroline)2 [(OP)2Cu(I)] provides a higher resolution picture of the site of enhanced binding. In particular, the sensitive footprinting afforded by (OP)2Cu(I) allows us to localize the major site of preferential interaction with propidium precisely to the branch point itself, with a roughly twofold symmetric pattern of cuts resulting. In detail, the differential pattern with respect to each duplex control is distinct for each arm of the junction. Excess propidium results in apparent reversal of the crossover isomer of the junction, indicating a possible additional avenue for the action of drugs in biological systems--effects on the products of recombination. PMID- 2105746 TI - Disruption of thymidylate synthesis and glycine-serine interconversion by L methionine and L-homocystine in Raji cells. AB - Excessive concentrations of L-methionine inhibited the folate-dependent de novo synthesis of thymidylic acid (TMP) in Raji cells, demonstrating the usefulness of this cell line for the study of methionine-folate antagonism. The effect was also produced by L-homocystine but not by other amino acids including D-methionine and L-ethionine, suggesting that this effect is exerted by a common intermediate of methionine and homocystine metabolism. L-Methionine, L-homocysteine, S adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) are not inhibitors of thymidylate synthase activity. On the other hand the capacity of the cells to incorporate serine 3-carbon and glycine 2-carbon into DNA is impaired by the presence of L-methionine or L-homocystine. Studies with cell-free extracts demonstrated that the glycine cleavage enzyme is inhibited by 45% by L methionine, L-homocysteine, SAM or SAH. Serine hydroxymethylase on the other hand was slightly stimulated by these sulfur-containing compounds and this stimulation was shown to occur in the intact cell as well. These findings suggest that when levels of L-methionine metabolites are elevated, there is an increase in the use of glycine to maintain the intracellular concentration of serine, which is required for homocysteine detoxification by conversion to cystathionine. The reduction in TMP synthesis caused by excess L-methionine or L-homocystine may result from increased utilization of one-carbon units for serine synthesis. PMID- 2105747 TI - The mechanism of Ca2+ stimulation of citrulline and N-acetylglutamate synthesis by mitochondria. AB - ATP-driven citrulline synthesis by mitochondria treated with oligomycin, uncoupler and Ca2+ ionophore is stimulated more than 2-fold by an increase in extramitochondrial free [Ca2+] in the range 1-5 microM. Stimulation increases with the length of preincubation of mitochondria with Ca2+. EGTA prevents stimulation if added at the start of the preincubation period, but is without effect if added at the end, suggesting that Ca2+ acts indirectly on citrulline synthesis via the accumulation of an intermediate. Neither carbamoyl-phosphate synthase (ammonia) nor ornithine carbamoyltransferase are stimulated by up to 50 microM free Ca2+ in mitochondrial extracts, but N-acetylglutamate synthase is stimulated about 30% by 10 microM free Ca2+. We propose that an increase in the activity of N-acetylglutamate synthase in response to an increase in free [Ca2+] in the mitochondrial matrix may contribute to hormonal stimulation of the urea cycle. PMID- 2105748 TI - In vivo metabolism of platelet-activating-factor (1-O-alkyl-2-acetyl-sn-glycero-3 phosphocholine) by the protozoan Tetrahymena pyriformis. AB - The metabolism of exogenous platelet-activating-factor was studied in the protozoan Tetrahymena pyriformis in vivo. When the cells are exposed to 1.10(-6) M PAF, the molecule is rapidly metabolized to 1-O-alkyl-2-acyl(long chain)-GPC, a major component of the protozoan membranes. The appearance of lyso-PAF from the first minutes even in low levels provides evidence that deacetylation is an intermediate step. After incubation for 30 min, transformation to aminoethyl phosphonolipids is also observed. The fate of PAF in concentrations 1.5.10(-11) M or 1.10(-8) M PAF, was the same. An amount of PAF depending on the external PAF concentration remained intact in the cell even after 1 h incubation. Our results suggest that the easily cultured protozoan can be a useful model for studying PAF's metabolism. PMID- 2105749 TI - Interaction of apolipoprotein A-II with recombinant HDL containing egg phosphatidylcholine, unesterified cholesterol and apolipoprotein A-I. AB - The preparation of discoidal, recombinant HDL (r-HDL) containing various phospholipids, apolipoproteins and a range of concentrations of unesterified cholesterol has been reported by several investigators. The present study describes the preparation of r-HDL containing both apolipoprotein (apo) A-I and apo A-II. r-HDL with 100:1 (mol:mol) egg PC.apo A-I and 0 (Series I), 5 (Series II) or 10 (Series III) mol% unesterified cholesterol were prepared by the cholate dialysis method. The resulting complexes had a Stokes' radius of 4.7 nm and contained two molecules of apo A-I per particle. When the r-HDL (2.0 mg apo A-I) were supplemented with 1.0 mg of apo A-II, one of the apo A-I molecules was replaced by two molecules of apo A-II. This modification was not accompanied by a loss of phospholipid, nor by major change in particle size. The addition of 2.5 or 4.0 mg of apo A-II resulted in the displacement of both apo A-I molecules from a proportion of the r-HDL and the formation of smaller particles (Stokes' radius 3.9 nm), which contained half the original number of egg PC molecules and three molecules of apo A-II. The amount of apo A-I displaced was dependent on the concentration of unesterified cholesterol in the r-HDL: when 2.5 mg of apo A-II was added to the Series I, II and III r-HDL, 44, 60 and 70%, respectively, of the apo A-I was displaced. Addition of 4.0 mg of apo A-II did not promote further displacement of apo A-I from any of the r-HDL. By contrast, the association of apo A-II with r-HDL was independent of the concentration of unesterified cholesterol and was a linear function of the amount of apo A-II which had been added. It is concluded that (1), the structural integrity of egg PC.unesterified cholesterol.apo A-I r-HDL, which contain two molecules of apo A-I, is not affected when one of the apo A-I molecules is replaced by two molecules of apo A II; (2), when both apo A-I molecules are replaced by apo A-II, small particles which contain three molecules of apo A-II are formed; and (3), the displacement of apo A-I from r-HDL is facilitated by the presence of unesterified cholesterol in the particles. PMID- 2105750 TI - In vivo and in vitro degradation of monofilament absorbable sutures, PDS and Maxon. AB - Two new absorbable monofilament suture materials polydioxanone and Maxon are being employed increasingly in abdominal surgery because of increased strength retention and decreased tissue reactivity compared with previously available materials. As part of our investigation of the behaviour of suture materials, 3-0 sutures of polydioxanone and Maxon were enclosed in nylon pouches, a technique developed for in vivo experiments to prevent cellular interaction with implanted devices. The pouched sutures were gas sterilized, then implanted in either the extrafascial space or peritoneal cavity for periods of 1-5 wk. Sterilized sutures were also incubated in Ringer's lactate at 37 degrees C. Tensile strength of the exposed sutures was measured. For a given suture material and duration of incubation, there was no significant difference in tensile strength degradation among the three test environments. Although the strength of unexposed Maxon is greater than that of polydioxanone, the residual strength of Maxon decreases more rapidly in use, so that, after 2 wk, the strength of polydioxanone is greater. Scanning electron microscope examination of the suture surfaces reveals that polydioxanone develops surface crazing with time, whereas the surface morphology of Maxon remains relatively unaltered. PMID- 2105752 TI - Housing and health: Accidents at home. PMID- 2105751 TI - Human gamma delta T-cell receptor-positive cell-mediated inhibition of erythropoiesis in vitro in a patient with type I autoimmune polyglandular syndrome and pure red blood cell aplasia. AB - The gamma delta T-cell receptor-positive (gamma delta TCR+) lymphocytes were markedly expanded up to 68% of peripheral blood lymphocytes in a case with type I autoimmune polyglandular syndrome and pure red blood cell aplasia (PRCA). The gamma delta TCR+ cells showed CD4 negative, 16% dim-CD8 positive and 10% to 46% human leukocyte antigen-D-related (HLA-DR) positive, and exhibited no monoclonality as assessed by the patterns of TCR gene rearrangements. Functional studies revealed that the proliferative responses of the patient's peripheral blood mononuclear cells (PBMC) were severely depressed to candida antigen, alloantigens, and autoantigens (non-T cells). The gamma delta TCR+ cells had no suppressive effect on the proliferative response of the alpha beta TCR+ cells to candida. The patient's PBMC, isolated gamma delta TCR+ cells but not alpha beta TCR+ cells, exhibited non-major histocompatibility complex (MHC)-restricted cytotoxicity. Furthermore, the patient's PBMC and isolated gamma delta TCR+ cells inhibited burst-forming units-erythroid (BFU-E), but not colony-forming units/granulocyte-macrophage (CFU-GM). Supernatants derived from the patient's T cells similarly inhibited BFU-E but not CFU-GM. The clinical course of the patient also showed a close correlation between the decreased number of total lymphocyte counts, especially HLA-DR + gamma delta TCR+ cell counts, and recovery from PRCA. These observations suggest that the gamma delta TCR+ cells might be functional in vivo and involved in the pathogenesis of PRCA in this patient. PMID- 2105753 TI - ABC of transfusion. Massive blood transfusion. PMID- 2105754 TI - Start and run a medical dining club. PMID- 2105755 TI - Variations in reported serum alkaline phosphatase activities. PMID- 2105756 TI - Aspirin use and chronic diseases. PMID- 2105757 TI - The cyclotron saga continues. PMID- 2105758 TI - Insertion of permanent pacemakers as a day case procedure. PMID- 2105759 TI - Child health surveillance. PMID- 2105760 TI - Passive smoking and cardiorespiratory health in Scotland. PMID- 2105761 TI - Congenital malformations. PMID- 2105762 TI - Convulsions in the older infant. PMID- 2105763 TI - Hearing problems of elderly people. PMID- 2105764 TI - Incidence of rheumatic fever. PMID- 2105765 TI - Interrelations in paediatric day stay surgery. PMID- 2105766 TI - Primiparous women using epidural analgesia. PMID- 2105767 TI - Duodenal carcinoid tumour in a patient with rheumatoid arthritis receiving long term ranitidine treatment. PMID- 2105768 TI - Laxative induced magnesium poisoning in a 6 week old infant. PMID- 2105769 TI - Sudden death after treatment with pulsed methylprednisolone. PMID- 2105770 TI - Monitoring research ethical committees. PMID- 2105771 TI - Adult polycystic kidney disease. PMID- 2105772 TI - HIV infection and tuberculosis. PMID- 2105773 TI - Medical audit. PMID- 2105774 TI - Britain bans oral snuff. PMID- 2105775 TI - Blood, HIV, and compensation. PMID- 2105776 TI - Individual variation between general practitioners in labelling of hypertension. AB - Variation in labelling of hypertension by individual general practitioners was studied during a continuous opportunistic screening programme for hypertension in a single general practice with 12 principals. All the general practitioners agreed to label as hypertensive patients with systolic pressures of greater than or equal to 200 mm Hg or diastolic pressures of greater than or equal to 110 mm Hg on three consecutive readings. The overall number of patients labelled hypertensive at the beginning of the screening programme was 505 and this rose to 801 after five years. There was a large variation in the numbers of patients recorded as hypertensive at the start of the screening period, with numbers ranging from eight to 112 for individual practitioners. The variation persisted during the screening period, with the numbers of patients detected by individual general practitioners ranging from four to 46. The average systolic and diastolic pressures recorded among these patients also varied between doctors, and only 24 out of 187 patients had their high pressures recorded on three occasions and so fully met the criteria for diagnosing hypertension. Clearly, general practitioners are following their own individual criteria in defining hypertension and taking into account factors other than just the measured blood pressure. PMID- 2105777 TI - Relation between systemic hypertension and sleep hypoxaemia or snoring: analysis in 748 men drawn from general practice. AB - OBJECTIVE: To establish whether a history of snoring or the degree of overnight hypoxaemia is an important independent predictor of systemic blood pressure. DESIGN: Prospective community based study of blood pressure in relation to overnight oxygen saturation, height, weight, and a questionnaire assessment of snoring, smoking, and alcohol consumption. Analysis was by multiple linear regression techniques and analysis of variance. SETTING: Small town outside Oxford, served by one group general practice of four partners. All measurements were made at home. SUBJECTS: The names of 836 men aged 35-65 were drawn at random from the general practitioners' age and sex register and the men then asked to participate; 752 (90%) agreed. MAIN OUTCOME MEASURES: Systolic, mean, and diastolic blood pressures and their association with age, obesity, alcohol consumption, cigarette consumption, snoring, and overnight hypoxaemia. RESULTS: Though systemic blood pressure correlated significantly with overnight hypoxaemia, this was due to the cross correlation with age, obesity, and alcohol consumption. No independent predictive effect of overnight hypoxaemia was found. Snoring was correlated with systemic blood pressure but not significantly so and also was not an independent predictor once age, obesity, and alcohol consumption had been allowed for. CONCLUSIONS: It is unlikely that snoring and sleep hypoxaemia from occult sleep apnoea are important causes of diurnal systemic hypertension when compared with age, obesity, and alcohol consumption. The increased prevalence of cardiovascular complications reported in snorers may be due to the confounding variable of obesity or to nocturnal rises in blood pressure that are not reflected in the daytime figures. PMID- 2105778 TI - Effective use of regional intensive therapy units. AB - OBJECTIVE: To determine the effectiveness of regional intensive therapy units. DESIGN: Retrospective and prospective study of patients transferred to a regional intensive therapy unit over four years. SETTING: Glasgow regional intensive therapy unit. MAIN OUTCOME MEASURES: Severity of illness was assessed at the time of referral to the unit with the acute physiological and chronic health evaluation (APACHE) scoring system. Mortality was calculated. RESULTS: A significant association was found between increasing duration of illness before transfer and mortality, which was independent of the severity of illness. Mortality also varied depending on the referring hospital. CONCLUSIONS: When transfer of critically ill patients is required this should be done as early as possible to make best use of the services available. The mortality of patients transferred after 10 days casts doubt on whether further aggressive intensive therapy is appropriate. PMID- 2105779 TI - Effect of intranasal oxygen on hypoxia and tachycardia during endoscopic cholangiopancreatography. PMID- 2105780 TI - The oesophagus in lichen planus: an endoscopic study. PMID- 2105781 TI - Current practice in transferring critically ill patients among hospitals in the west of Scotland. AB - OBJECTIVE: To identify the requirements of an interhospital transfer service for critically ill patients. DESIGN: Retrospective survey of the current functions of a specialist interhospital transfer team from data collected at the time of transfer and from records of intensive care unit. SETTING: Mobile intensive care unit based at a tertiary referral centre, which serves the west of Scotland. PATIENTS: All critically ill patients (378) transferred between hospitals by the unit from 1986 to 1988. RESULTS: 365 Patients were transferred by road and 13 by air. There was a wide variation in age (range 6 weeks to 87 years), diagnosis, reason for transfer, support required, and distance travelled. Most patients (232) were transferred for respiratory or cardiovascular support; 100 were trauma cases. 300 Patients (79%) were mechanically ventilated during transfer. No patient died in transit, although the eventual mortality was 28% (105 patients). Mortality was significantly higher in patients transferred from hospitals with intensive care units than from those without (38% (125 patients) v 23% (253); p less than 0.005). IMPLICATIONS: Safe interhospital transfer of critically ill patients is feasible; the high eventual mortality in some patient groups emphasises the need for accurate prediction of outcome if inappropriate transfer is to be avoided. The findings may help in organising secondary transfer services in future. PMID- 2105783 TI - Defining essential data for audit in general practice. PMID- 2105782 TI - Avoidable factors contributing to death of children with head injury. AB - OBJECTIVE: To assess the incidence of potentially avoidable complications contributing to death of children with head injuries. DESIGN: Retrospective review of children who died with head injuries from 1979 to 1986 from data of the Office of Population Censuses and Surveys, Hospital Activity Analyses, case notes, coroners' records, and necropsy reports. SETTING: District general hospitals and two regional neurosurgical centres in Northern region. RESULTS: 255 Children died from head injury in the region, the mortality being 5.3 per 100,000 children per year. Head injury was the single most important cause of death in children aged greater than 1 year, accounting for 15% of deaths in children aged 1-15 years and a quarter for those aged 5-15 years. 121 Potentially avoidable factors possibly or probably contributing to death occurred in 81 children (32%). Half the children (125) died before admission, 27 of whom (22%) had potentially avoidable factors possibly or probably contributing to death, and 130 died after admission, 54 of whom (42%) had 93 such factors, which included failure of diagnosis or delayed recognition of intracranial haemorrhage or associated injury, inadequate management of the airways, and poor management of the transfer between hospitals. IMPLICATIONS: Regions should revise urgently their guidelines for optimal management and indications for neurosurgical referral to include children with severe head injuries and audit their systems of care for all patients with head injuries. PMID- 2105784 TI - Contribution of regional specialty subcommittees to organising audit. PMID- 2105785 TI - Knowledge and experience of young people regarding drug abuse, 1969-89. AB - OBJECTIVE: To establish a baseline of knowledge to plan an effective health education programme in schools. The survey was repeated at five year intervals from 1969 to 1989. DESIGN: To preserve consistency, the same anonymous questionnaire, which was confidential to the research workers, was used throughout. SETTING: Three secondary schools in Wolverhampton in different parts of the town and representing different social groups. SUBJECTS: Sample sizes ranged from 471 fourth year pupils (aged 14 to 15) in 1969 to 540 in 1984 and 380 in 1989, the decrease being due mainly to the falling birth rate. There were slightly more girls than boys, and the pupils covered the whole range of academic ability. RESULTS: Over the 20 years the proportion of pupils who knew someone taking drugs more than doubled from 15% (71) to 31% (117) and the proportion who had been offered drugs almost quadrupled from 5% (24) to 19% (72). The changes taking place over the past five years were characterised by an increased knowledge about drugs and the first mention of "crack," a purified form of cocaine, and "ecstasy" (methylenedioxymethamphetamine). Peer influence continued to be given as the prime reason for taking drugs. Over the 20 years, though less often mentioned in 1989, television and newspapers remained the most common source of information. CONCLUSIONS: These results suggest the need for responsible coverage by the mass media and for more effective health and social education programmes to prevent the spread of drug misuse. PMID- 2105786 TI - Solvent abuse. PMID- 2105787 TI - Nibblers, gorgers, snackers, and grazers. PMID- 2105788 TI - Rabies in Britain. PMID- 2105789 TI - University hospitals and the NHS review. PMID- 2105790 TI - The dystonias. PMID- 2105791 TI - "You've almost got to die of your disease to get treated". PMID- 2105792 TI - Immunoscintigraphy for detecting acute myocardial infarction without electrocardiographic changes. AB - OBJECTIVE: To establish whether immunoscintigraphy with antibody to myosin may detect acute myocardial infarction without electrocardiographic changes. DESIGN: Prospective study of patients with suspected acute myocardial infarction or unstable angina with cardiac imaging with 111indium myosin antibody, estimation of cardiac enzyme concentrations, electrocardiography, 201thallium imaging, and radionuclide ventriculography. SETTING: Coronary care unit in a district general hospital. PATIENTS: 119 Consecutive patients with suspected acute myocardial infarction or unstable angina. Patients with cardiomyopathy, myocarditis, valvular heart disease, myocardial infarction or cardiac surgery in the previous two weeks or with left bundle branch block and women of childbearing age were excluded. RESULTS: Of 75 patients with suspected acute myocardial infarction, seven had no diagnostic electrocardiographic changes despite normal conduction patterns. Immunoscintigraphy with myosin antibody disclosed necrosis in all seven patients, which was localised in regions supplied by diseased coronary arteries in all but one. Six patients had abnormal images on 201thallium imaging, and all seven had abnormal wall motion at the site of antibody uptake. One patient with minimal left main stem and right coronary artery atheroma had uptake of antibody at two discrete sites. CONCLUSIONS: Immunoscintigraphy with antibody to myosin confirms myocardial infarction in the absence of electrocardiographic changes and discloses the site of infarction. PMID- 2105793 TI - Recurrent spontaneous abortion and polycystic ovarian disease: comparison of two regimens to induce ovulation. AB - OBJECTIVE: To determine whether pituitary suppression before induction of ovulation reduces the rate of spontaneous abortion in women with polycystic ovarian disease and primary recurrent spontaneous abortions. DESIGN: Closed, randomised, sequential trial. Pairs of women were allocated to each treatment by the toss of a coin. SETTING: Supraregional clinic for women who had had recurrent spontaneous abortions. SUBJECTS: Forty two women with polycystic ovarian disease and primary recurrent spontaneous abortions. INTERVENTIONS: Ovulation was induced by clomiphene or pituitary suppression with buserelin followed by pure follicle stimulating hormone. MAIN OUTCOME MEASURES: Preference for a particular treatment was noted. A preference occurred when one woman in a pair had a successful pregnancy (defined as one of over 12 weeks' gestation) and one had a spontaneous abortion; the preference was for the treatment resulting in the successful pregnancy. RESULTS: Spontaneous abortions occurred in 11 of 20 women given clomiphene compared with two of 20 who had pituitary suppression. Eleven preferences were found for buserelin and two for clomiphene. In seven pairs both women had successful pregnancies. One pair was discarded because one of the women did not become pregnant. The ratio of luteinising hormone concentration to follicular diameter was found to be a possible diagnostic indicator of spontaneous abortion. CONCLUSION: Pituitary suppression before induction of ovulation significantly reduces the risk of spontaneous abortion in women with polycystic ovarian disease and primary recurrent spontaneous abortions. PMID- 2105794 TI - General practitioner response to elderly patients discharged from hospital. AB - OBJECTIVE: To determine the effect of discharge information given to general practitioners on their management of newly discharged elderly patients. DESIGN: A random sample of 133 elderly patients who had unplanned readmission to a district general hospital within 28 days of discharge was compared with a matched control sample of patients who were not readmitted. Information was gathered from the hospital, the patients, the carers, and the general practitioners about the information that the hospital had sent the general practitioner and the general practitioners' response to this information. SETTING: All specialties in a district general hospital. PATIENTS: 266 Patients aged over 65 representative in the main demographic indices of the population of elderly patients admitted to hospital. RESULTS: Ten weeks after discharge the doctors had received notice of discharge about 169 of the patients, but fewer than half the discharge notices were received within the first week. General practitioners were dissatisfied with the information in 60 cases. A general practitioner visited 174 of the patients after their discharge from hospital and three quarters of the visits took place within two weeks of the discharge. These visits were more likely to have been initiated by patients or families than by the doctor, and this was not influenced by the doctor receiving notice of the patient's discharge. Older patients and those who had carers were the most likely to be visited. Nearly half of the carers were dissatisfied with some aspect of general practitioner care, problems with home visiting being the commonest source of complaint. CONCLUSIONS: Hospital communications to general practitioners about the discharge of elderly patients still cause concern, particularly in the time they take to arrive. Written instruction to vulnerable elderly patients asking them to inform their general practitioner of the discharge might be helpful. Carers complained of lack of support, and it is clearly important for someone (either the general practitioner or another health worker) to visit elderly people shortly after their discharge. PMID- 2105795 TI - Measuring blood pressure in the elderly: does atrial fibrillation increase observer variability? AB - OBJECTIVE: To compare the interobserver and intraobserver variability of blood pressure measurements in geriatric patients in atrial fibrillation and in sinus rhythm. DESIGN: Prospective assessment of blood pressure measurements carried out in random order in two groups of elderly patients by five doctors unaware of the aims of the study. SETTING: Acute assessment wards for geriatric medicine, Cardiff Royal Infirmary. PATIENTS: 50 Elderly patients in sinus rhythm and 50 in atrial fibrillation. MAIN OUTCOME MEASURES: Interobserver and intraobserver variability of blood pressure measurements in the two groups expressed as the coefficient of variability and compared by the Mann-Whitney U test. RESULTS: Interobserver variability was significantly greater in the patients with atrial fibrillation for both systolic and diastolic pressures. Intraobserver variability was significantly greater in the atrial fibrillation group for diastolic pressures but the difference was not significant for systolic pressures. These differences were not related to pulse rate, age, or level of blood pressure. CONCLUSIONS: The findings suggest that in the presence of atrial fibrillation physicians' interpretations of Korotkoff sounds are less uniform, which may have important clinical implications. Possibly a standardised methodology may overcome this problem. PMID- 2105796 TI - Postural hypotension related to zidovudine in a patient infected with HIV. PMID- 2105797 TI - Dupuytren's contractures in patients infected with HIV. PMID- 2105798 TI - Training in accident and emergency: views of senior house officers. PMID- 2105799 TI - Diving practices of scuba divers with asthma. PMID- 2105800 TI - Should fertile people have access to in vitro fertilisation? PMID- 2105801 TI - General practice computing in Scotland. AB - OBJECTIVE: To investigate a method of assessing the extent of routine patient data held on computer by Scottish general practitioners. DESIGN: An "electronic questionnaire" in the form of an interrogation questionnaire was used to extract a subset of data from practice computers running a standard software package (the general practice administrative system for Scotland, GPASS). The data were retained by each practice and also collected and analysed centrally to produce regional and national data. SUBJECTS: All 257 general practices in Scotland using GPASS software were sent the electronic questionnaire; data from 154 practices, including 759 general practitioners and covering 1,010,452 patients, were collected. RESULTS: Ninety three practices had all their patient records on computer; others had selectively entered data on, for example, only those patients receiving repeat prescriptions. The number of computerised patient records per practitioner ranged from 46 to 2373. Altogether 194,261 patients had repeat prescribing data and 204,005 morbidity or clinical data. CONCLUSION: An electronic questionnaire is a simple and effective way of investigating the information held on practice computers, allowing analysis and feedback of information to practitioners. Development of this system will provide a cumulative information system for Scottish general practitioners. PMID- 2105802 TI - ABC of transfusion. Immunological complications of transfusion. PMID- 2105803 TI - Housing and health: sanitation. PMID- 2105804 TI - How to do it. Organise a multicentre trial. PMID- 2105805 TI - Fibromuscular dysplasia of renal arteries: a neglected cause of acute loin pain. PMID- 2105806 TI - AIDS stigma in insurance market. PMID- 2105807 TI - Selective decontamination of the digestive tract. PMID- 2105808 TI - The cyclotron saga continues. PMID- 2105809 TI - Abuse of mentally handicapped adults. PMID- 2105810 TI - Diagnostic and therapeutic efficacy of barium meal examination. PMID- 2105811 TI - Transabdominal ultrasound screening for early ovarian cancer. PMID- 2105812 TI - Spare artificial legs. PMID- 2105813 TI - Brisk walking and high density lipoprotein cholesterol. PMID- 2105814 TI - Oral contraceptives and diabetes mellitus. PMID- 2105815 TI - When risk factors have little meaning. PMID- 2105816 TI - Cross species applicability of psychiatric diagnosis and treatment. PMID- 2105817 TI - Case of simultaneous diverticulosis, lipomatosis and volvulus of the small intestine. PMID- 2105818 TI - Drug therapy for Parkinson's disease in the elderly. AB - The diagnosis and management of Parkinson's disease in the elderly is complicated by the common presence of multiple pathology and age related changes in drug handling. Accurate diagnosis requires a high index of suspicion combined with careful assessment before and after a trial of therapy. A multidisciplinary approach is required to help the patient, and their carer, cope with the fundamental disabilities resulting from Parkinson's disease. The elderly are more susceptible to side effects from antiparkinsonian medication and close supervision is therefore essential. PMID- 2105819 TI - Evidence for thyrotropin-releasing hormone and glucocorticoid receptor immunoreactive neurons in various preoptic and hypothalamic nuclei of the male rat. AB - Neurons containing thyrotropin-releasing hormone (TRH) and glucocorticoid receptor (GR) immunoreactivity (IR) were demonstrated by a two-colour immunoperoxidase method in coronal cryotome sections of the preoptic region and the hypothalamus of the male rat brain. All the TRH-IR neurons (TRH-IR) located in the dorsal hypothalamus - medial and dorsal parvocellular parts of the paraventricular hypothalamic nucleus and the dorsomedial hypothalamic nucleus - and in the anterior periventricular hypothalamic nucleus were strongly GR-IR. The TRH-IR neurons of the medial preoptic area, the perifornical nucleus and the medial tuberal area were mostly weakly GR-IR and some lacked GR-IR. These data indicate a differential regulation of diencephalic TRH-IR neurons by glucocorticoids. They also imply that the inhibitory effect of glucocorticoids on TSH secretion may involve a direct inhibition of TRH synthesis and/or release by a nuclear action in the TRH-IR nerve cells of the paraventricular hypothalamic nucleus projecting to the median eminence. PMID- 2105820 TI - Fetal dopamine neuron transplants prevent behavioral supersensitivity induced by repeated administration of L-dopa in the rat. AB - We have studied in adult rats bearing a unilateral nigral lesion the effect of nigral grafts into the striatum on behavioral supersensitivity induced by chronic treatment of L-DOPA (100 mg/kg i.p.) plus benserazide (50 mg/kg i.p.). Repeated administration of L-DOPA increases contraversive circling. In rats without graft the contraversive circling was significantly increased after 8 and 14 daily injections of L-DOPA. On the other hand, the animals with transplants showed no such increase. Behavioral supersensitivity induced by repeated treatment of L DOPA is often correlated with dyskinesia observed in the Parkinsonian patients. This suggests that the graft might be able to prevent this secondary effect. PMID- 2105821 TI - Extracellular oxytocin in the paraventricular nucleus: hyperosmotic stimulation by in vivo microdialysis. AB - The effect of central osmotic stimulation on oxytocin (OT) secretion from the paraventricular nucleus (PVN) was examined using a newly developed in vivo microdialysis technique. A dialysis probe was inserted into the PVN region and microdialysis was performed in conscious animals. Hyperosmotic solutions were delivered via the dialysis probe, and perfusate and blood samples were collected. OT was consistently detected in the PVN dialysate. Hyperosmotic sodium chloride (1 M) produced a significant increase in dialysate and plasma OT, whereas D mannitol (2 M) had no effect. These results suggest that (1) in vivo microdialysis may provide a useful technique for the evaluation of neuropeptide secretion from specific brain regions and (2) there are sodium-sensitive cells in the PVN region which respond to increases in extracellular sodium, resulting in an increase in central and peripheral oxytocin secretion. PMID- 2105822 TI - Serotonin (5-HT) induces IPSPs in pyramidal layer cells of rat piriform cortex: evidence for the involvement of a 5-HT2-activated interneuron. AB - In a slice preparation of rat piriform cortex, both intracellular and extracellular techniques were used to examine the pharmacological and electrophysiological actions of serotonin (5-HT). Bath application of 5-HT resulted in either depolarization (57%), hyperpolarization (34%) or no change (9%) in membrane potential of cells in the pyramidal cell layer (layer II) of piriform cortex. Additionally, when KCl-containing electrodes were used, 5-HT induced an increase in depolarizing synaptic potentials in 41% of these cells. It was concluded that these potentials were reverse inhibitory post-synaptic potentials (IPSPs) because they were blocked by bicuculline and tetrodotoxin. The induction of IPSPs by 5-HT was blocked by the 5-HT2-selective antagonist ritanserin. By recording extracellularly in the presence of 5-HT, a group of 5-HT activated, putative interneurons was found at the border of layers II and III of piriform cortex, 5-HT but not norepinephrine activation was blocked by ritanserin. The actions of 5-HT were mimicked by the 5-HT2 agonist alpha-methyl-5 HT; the 5-HT2 partial agonist, 2,5-dimethoxy-4-methyl-amphetamine had a small agonist action of its own and blunted the effect of 5-HT. Activation of a larger group of putative interneurons by the more universal excitant N-methyl-D aspartate showed that the 5-HT-activated interneurons represented 23% of the interneurons located on the border between layers II and III. We conclude that 5 HT induces IPSPs in layer II pyramidal cells by activating a subpopulation of interneurons at the border of layers II and III of piriform cortex. PMID- 2105823 TI - Lack of change in striatal DARPP-32 levels following nigrostriatal dopaminergic lesions in animals and in parkinsonian syndromes in man. AB - The present study was performed to determine the effect of a nearly complete nigrostriatal dopaminergic denervation on DARPP-32 levels in the striatum from animals and parkinsonian patients. DARPP-32 levels were estimated by in vitro phosphorylation in the presence of cAMP, or after inactivation of endogenous kinases and phosphatases, in the presence of the catalytic subunit of cAMP dependent protein kinase. Intranigral 6-hydroxydopamine (6-OHDA) infusion in rats, or peripheral administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) to common marmosets, did not change striatal DARPP-32 levels. Postmortem studies, carried out on brains obtained shortly after death, from patients with Parkinson disease, or from patients with progressive supranuclear palsy, showed that the levels of striatal DARPP-32 were not different from controls. These results indicate that dopaminergic striatal denervation did not modify the amount of DARPP-32 in the striatum, suggesting that the expression of DARPP-32, a protein which mediates some of the effects of dopamine in striatal neurons, is independent from the dopaminergic innervation. PMID- 2105824 TI - Functional recovery after destruction of dopamine systems in the nucleus accumbens of rats. I. Behavioral and biochemical studies. AB - Bilateral 6-hydroxydopamine (6-OHDA) lesions in the nucleus accumbens of rats induced motor hypoactivity 7 days after the lesion. Spontaneous functional recovery of this impaired behavior occurred in 3-4 weeks. Behavioral and biochemical studies suggest that the hypoactivity is due to damage of the dopamine systems in the nucleus accumbens. The 6-OHDA lesions induced a decrease in the nucleus accumbens levels of dopamine and its metabolites of about 30% both 7 and 20 days after the lesion. The in vitro uptake of [3H]dopamine in nucleus accumbens tissue of the 6-OHDA-lesioned rats was decreased to the same extent at 7, 14 and 28 days after the lesion. Scatchard analysis of [3H]haloperidol binding studies in nucleus accumbens tissue revealed a shift from one type of binding site in tissue of sham-lesioned rats to two types of binding sites in tissue of 6 OHDA-lesioned rats 29 days after the lesion. This shift was not present in nucleus accumbens tissue 8 days after a 6-OHDA lesion. The spontaneously recovered rats showed an enhanced behavioral response upon administration of the dopamine agonist apomorphine. The present data suggest that the spontaneous functional recovery of impaired motor activity is caused by the development of supersensitivity of the dopamine receptor systems in the nucleus accumbens. This supersensitivity may be the result of increased affinity of one type of binding site or an increased number of functional binding sites. PMID- 2105825 TI - Requirement for G protein activity at a specific time during embryonic chick myogenesis. AB - Signaling between embryonic myoblasts involves prostaglandin metabolism, the activation of a membrane receptor and changes in polyphosphatidyl inositol metabolism. Many of these membrane-localized events occur between 33 to 35 h of differentiation, concomitant with a dramatic change in membrane organization, in myoblast aggregates in culture. Since many receptors affect inositol phosphate metabolism by activating a GTP-binding protein (G protein), we asked if there was evidence for such a protein in myogenic signaling. We show that during the period of differentiation in culture when prostaglandin is needed to bind to a transient receptor, a pertussis toxin-sensitive but cholera toxin-insensitive G protein must act. If this activation is blocked, the characteristic change in myoblast cell adhesion and subsequent membrane fusion do not occur. We suggest that a G protein couples the activated prostaglandin receptor and the change in polyphosphatidyl inositol metabolism and that this membrane transduction step is necessary for subsequent membrane differentiation events during myogenesis. PMID- 2105826 TI - Phalloidin inhibits cortical granule exocytosis and ooplasmic segregation in loach eggs. AB - Injections of phalloidin under the surface of loach eggs, followed by activation of the eggs in tap water, result in local inhibition of cortical granule (CG) exocytosis. Light and electron microscopy revealed that in the region where exocytosis is inhibited the thickness of the microfilamentous cortex (MC) separating CGs from the plasma membrane (PM) is increased significantly, and many CGs are detached and have moved away from the MC. Injections of phalloidin also inhibit ooplasmic segregation in fertilized eggs. The experiments suggest that in intact eggs the MC represents a physical barrier to CG exocytosis, and that interactions of the MC with the PM and CGs are crucial for the retention of CGs near the sites of fusion. PMID- 2105827 TI - Symposium: New approaches to the diagnosis and treatment of hypercalcemia. Presented at the first joint meeting of the International Conferences on Calcium Regulating Hormones and the American Society for Bone and Mineral Research. Montreal, Canada, September 1989. PMID- 2105828 TI - Assessment of renal and skeletal components of hypercalcemia. AB - The management of hypercalcemia of malignancy is guided by assessments of its various components. Since the intestine usually makes no contribution to hypercalcemia under these circumstances, the problem is to measure the net efflux of calcium out of bone and the ability of the kidneys to excrete the unwanted calcium load. Established relationships between serum and urinary calcium excretion rates allow the quantitation of the relative contribution of an impaired glomerular filtration rate, of reduced renal tubular calcium reabsorption, and of increased bone resorption. Since the renal handling of calcium is closely related to that of sodium in the proximal nephron, the rate of sodium excretion is an important variable in these measurements. A practical approach to the separation of hypercalcemia into its renal and skeletal components is described in this article. Examples of how these measurements can be used to assess the responses to various types of therapy for malignancy associated hypercalcemia are also given. PMID- 2105830 TI - Alloimmunization and intravenous drug abuse. PMID- 2105831 TI - Neoplasms of the peripheral nervous system. AB - Neoplasms of the peripheral nervous system arise from the cellular sheath surrounding the nerve trunks, that is, the pluripotential Schwann cells and related cells, and rarely affect the feet. When present, they are most frequently associated with the autosomal dominantly inherited neurofibromatosis 1. This condition has been related to chromosome 17, and it appears, from in vitro experiments, to involve defects in tyrosine metabolism. Hence, the most common neoplasm is the neurofibroma. Distinct criteria have been established for a diagnosis of neurofibromatosis 1, so that a single pedal neurofibroma may not represent this complex. However, if the complex is present, it is necessary to consider the possibility of malignant transformation to a neurofibrosarcoma. Although malignant peripheral nerve neoplasms are extremely rare in the feet, they may arise in the context of neurofibromatosis 1, or independently. Other benign or malignant schwannomas may (rarely) also arise in the feet. Surgical excision of benign lesions, according to established standards for tumor surgery, is usually curative, but a detailed personal and familial history, along with adjunctive radiologic procedures and biopsy, is necessary to determine the nature of the lesion. Since (endocrine and) other abnormalities may complicate neurofibromatosis 1, surgical procedures must not be undertaken until the patient has been medically cleared and is carefully monitored. A high mortality rate is associated with malignant peripheral neurogenic tumors, especially those arising in the context of neurofibromatosis 1. It should be recalled that neurologic manifestations in the foot may represent non-neoplastic conditions as well as peripheral nerve tumors (or other tumors involving those nerves) that are proximal to the foot and ankle area. PMID- 2105829 TI - Incidence and pathophysiology of hypercalcemia. AB - Hypercalcemia occurs for various reasons in patients with malignant diseases. Most of these patients show a relative increase in bone resorption over bone formation. Increased renal tubular calcium reabsorption is also important for maintaining hypercalcemia in the majority of patients. Calcium absorption from the gut is usually decreased. In a few patients, fixed impairment of glomerular filtration contributes to hypercalcemia. Because the pathophysiology of hypercalcemia is heterogeneous, it may be considered as three separate syndromes: the humoral hypercalcemia of malignancy caused by systemic mediators; the hypercalcemia associated with localized osteolytic disease; and the hypercalcemia associated with myeloma and related hematologic malignancies. Increased bone resorption is a key feature in each of these syndromes. In malignant disease, bone resorption is enhanced because osteoclast activity is increased by the production of humoral mediators. These mediators are often produced by the tumor cells but are also produced by normal host cells that have been activated by the presence of the tumor. some of these mediators of hypercalcemia are systemic factors, but some act only locally. They include parathyroid hormone-related protein, transforming growth factor alpha, lymphotoxin, tumor necrosis factor, interleukin-1 alpha and 1,25-dihydroxyvitamin D. PMID- 2105832 TI - Current issues in cancer rehabilitation. AB - Many patients with cancer enjoy long-term survival and are cured; others may live for extended periods while receiving specific treatment for cancer. This has been accomplished with increasingly complex and multimodal therapy, along with heightened toxicity and longer treatment. Cancer has become a chronic disease for many patients. Contemporary cancer rehabilitation provides a coordinated approach that addresses the physical, psychosocial, vocational, and economic concerns of the patient. Key components of a cancer rehabilitation program should include initial needs assessment with periodic reassessments, direct provision of specific interventions, and referrals to appropriate community resources. Almost all patients with cancer can benefit from a rehabilitation assessment and intervention. Important rehabilitation issues include the physical toxicity of treatment, psychosocial concerns, sexual dysfunction, diet and nutritional concerns, pain management, and vocational and economic problems. Patient groups with unique rehabilitation problems include patients with head and neck cancer or breast cancer, and patients who have undergone osteotomies or amputations. Long term cancer survivors also have special rehabilitation needs that relate to the delayed effects of treatment on normal tissues, gonadal dysfunction, second neoplasms, employment discrimination, and difficulties obtaining health and life insurance coverage. Rehabilitation assessment and intervention should be incorporated into the routine health care of patients with cancer. PMID- 2105833 TI - Concomitant continuous infusion chemotherapy and radiation. AB - Attempts to duplicate the cytotoxic effect of oxygen on radioresistant tissues spurred a search by radiation oncologists for other radiosensitizing techniques. This led to large-scale investigations using neutrons and other heavy particle radiations, hyperthermia, altered fractionation schedules, and the systemic use of the halogenated pyrimidines and the electron-affinic compounds. Unfortunately, the promise that the nitroimidazole compounds would selectively sensitize the radioresistant tumor cells and prove to be an effective systemic agent has not been borne out in clinical trials thus far. Existing pharmokinetic and cytokinetic studies have suggested that continuous infusion chemotherapy given concomitantly (CCIC) with irradiation (RT) acts synergistically, resulting in a significant increase in tumor cell killing. These observations have been supported by clinical research studies treating certain epithelial cancers that have resulted in considerably higher locoregional control rates and improved survival. Although initially used in treatment of only advanced or inoperable epithelial carcinomas, CCIC and RT are now being employed in the treatment of lower staged cancers as an organ-sparing procedure. Carcinoma of the anus treated by anteroposterior (AP) resection alone have reported 5-year survival rates of 30% to 60%. CCIC and RT using 5-fluorouracil (5-FU) and mitomycin C have achieved a local control rate of 90% to 100% and a 5-year survival rate of 80% to 86% with sphincter preservation in 90% of these cases. The 5-year survival rate in advanced urinary bladder carcinoma is 25% to 30% for either radiation or surgery and 42% when combined in a preoperative radiation schedule. Using 5-FU CCIC and RT, the local control rate of transitional cell carcinoma of the bladder has been 71% to 86% with a 5-year survival of 62%. 5-FU CCIC and cisplatin and RT used in the treatment of Stages III and IV carcinoma of the cervix yields a locoregional control of 74% compared with the radiation alone local control of 63% for Stage III and 30% for Stage IV disease. Advanced head and neck and paranasal sinus carcinomas treated by cisplatin CCIC and RT show improved tumor clearance even in the presence of bone destruction. A complete response rate of 87% has been reported with the use of cisplatin CCIC and hyperfractionated radiation. Hyperfractionated radiation also appears to improve the local control of advanced head and neck cancers over patients treated with single fractions of radiation with 66% surviving at 22 months.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2105834 TI - Induction of cutaneous mast cell tumors by N-methyl-N'-nitro-N-nitrosoguanidine followed by TPA in female mice of 4 out of 5 strains tested. AB - Appreciable yields of cutaneous mast cell tumors were induced in a two-stage skin carcinogenesis protocol comprising N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) initiation followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in 4 of 5 strains of mice. Only female mice of each of the 5 strains were studied. The incidences of benign and/or malignant lesions differed considerably between strains; 27% in DBA/2, 22% in BDF1, 11% in BALB/c, 10% in CDF1 and 0% in C57BL/6 mice and no mast cell tumors were detected in any of the strains when treated with the initiator alone. First found in a DBA/2 mouse at week 50, most tumors were observed after 100 weeks of promotion, and were usually small in size (less than 2 mm in diameter) and predominantly located within the corium, although they occasionally extended into the subcutaneous tissue. Histologically, the benign mast cell tumors were composed of non-encapsulated, well circumscribed densely packed sheets of discrete cuboidal or rhomboid cells. Metachromatic granules were clearly visible in the cytoplasm by Toluidine Blue staining. Two of the tumors induced in DBA/2 mice were diagnosed as malignant mast cell tumors on the twin bases of cellular atypia and deep infiltration into the muscular layer. The cutaneous mast cell tumors were constantly accompanied by subepidermal mast cell aggregations which were also commonly observed in tumor-free skin of mice receiving the initiation-promotion procedure. PMID- 2105835 TI - Bladder epithelial hyperplasia in F344 rats after intravesical instillation of the antitumor chemotherapeutic agents Adriamycin and mitomycin C. AB - The effects of intravesical instillation of the antineoplastic antibiotics, Adriamycin or mitomycin C, on the urinary bladder epithelium of female F344 rats were evaluated using a combined immunohistochemical and morphological approach. Four weeks treatment with Adriamycin or mitomycin C induced an increase of DNA synthesis and was associated with simple hyperplasia characterized by elevated nuclear cytoplasmic ratios, cytomegaly and pleomorphism. Under the scanning electron microscope (SEM), luminal cell surface alterations such as pleomorphic microvilli were observed. Severity of the lesions was greatest in the Adriamycin group and although treatment of the saline vehicle alone also brought about development of simple hyperplasia, this was very slight and not accompanied by cellular pleomorphism. The present results demonstrated that intravesical instillation of antineoplastic agents can cause a proliferative response and cytotoxicity after only short-term treatment and suggest that this chemotherapy could itself play a possible role in promotion of bladder carcinogenesis or cancer development. PMID- 2105836 TI - Formation and persistence of DNA adducts in the liver of brown bullheads exposed to benzo[a]pyrene. AB - The formation and persistence of benzo[a]pyrene (BP)-DNA adducts in the liver of brown bullheads (Ictalurus nebulosus) treated with the hydrocarbon (20 mg/kg body wt, i.p.) was investigated using the 32P-postlabeling assay. The highest level of covalent binding of BP to liver DNA (188 fmol BP adducts/mg DNA) was observed 25 30 days following treatment. After 70 days, the adduct level in liver DNA had declined to approximately 26% of the maximum adduct level. One major BP-DNA adduct and several minor ones were detected in the liver. The major adduct co chromatographed with anti-BP-7,8-diol-9,10-epoxide-deoxyguanosine (anti-BPDE dGuo) adduct. The data suggest that brown bullheads metabolically activate BP by the same mechanism as the mammalian systems susceptible to carcinogenic effects of the hydrocarbon. PMID- 2105837 TI - Maintenance and cure of the L5178Y murine tumor-dormant state by interleukin 2: dependence of interleukin 2 on induced interferon-gamma and on tumor necrosis factor for its antitumor effects. AB - We reported previously that treatment of peritoneal cell (PC) cultures prepared from mice which harbor L5178Y lymphoma cells in a tumor-dormant state in their peritoneal cavity with interleukin 2 (HuIL-2) stimulated antitumor cytotoxic activity in both the nonadherent and adherent populations derived from such cultures. We report here that HuIL-2 induced the production of murine gamma interferon (MuIFN-gamma) in these PC cultures and required Lyt-1-, Lyt-2-, and L3T4-expressing lymphocytes to do so. HuIL-2 required and synergized with this induced MuIFN-gamma to stimulate cytotoxic activity in the nonadherent PC and the MuIFN-gamma itself stimulated cytotoxic activity in the adherent PC. Cyclosporin A prevented both the induction of MuIFN-gamma and the development of antitumor cytotoxic activity in HuIL-2-treated PC cultures. An addback of exogenous MuIFN gamma to HuIL-2-cyclosporin A-treated PC cultures and to the nonadherent subpopulation of such cultures, at a concentration which itself produced no antitumor effect, permitted HuIL-2 to induce its antitumor effect. We previously reported that MuIFN-gamma requires the action of murine tumor necrosis factor (MuTNF) to induce cytotoxic activity in PC cultures from tumor-dormant mice. We report here that HuIL-2 also requires the action of (MuTNF) to stimulate antitumor cytotoxic activity in PC cultures from tumor-dormant mice. These results indicate that HuIL-2 induces MuIFN-gamma and requires and synergizes with this MuIFN-gamma and with (MuTNF) to stimulate antitumor cytotoxic activity in PC cultures from tumor-dormant mice. PMID- 2105838 TI - Relationship between metastatic ability and H-ras oncogene expression in rat mammary cancer cells transfected with the v-H-ras oncogene. AB - To study the relationship between metastatic ability and activated ras expression, a cloned, low metastatic, dimethylbenz(a)anthracene-induced rat mammary cancer cell line (RMC1) was transfected with the v-H-ras oncogene. Cloned transfectants were characterized as high, medium, or low expressors of the v-H ras gene, on the basis of Southern, Northern, and Western blot analysis. Following s.c. inoculation in syngeneic rats, all transfectants produced tumors; however, the in vivo growth rate of cloned transfectants which expressed any level of v-H-ras oncogene was significantly higher (approximately 5-fold) than that observed in the untransfected RMC1 cells. Control (neo only) transfectants exhibited no change in growth rate and had a low metastatic ability comparable to that of the parental untransfected cells. Certain cloned v-H-ras expressing transfectants were highly metastatic to the lungs and lymph nodes. These highly metastatic H-ras transfectants differed widely however, in their level of H-ras expression. The lung colonization potential following i.v. inoculation was increased in all transfectants which expressed any level of v-H-ras gene. These studies suggest that while v-H-ras transfection can result in the development of metastatic ability in rat mammary cancer cells, there is no simple dose-response relationship between the level of v-H-ras expression in cloned rat mammary cancer cell transfectants and the development of experimental or spontaneous metastases. PMID- 2105839 TI - Protein and messenger RNA levels of plasminogen activators and inhibitors analyzed in 22 human tumor cell lines. AB - In 22 human tumor cell lines the regulation of production of plasminogen activators urokinase (u-PA) and tissue-type (t-PA) and their inhibitors PAI-1 and PAI-2 was studied. These four components may determine the net plasminogen activator activity, which is often associated with tumor development and metastatic processes. The amount of specific mRNA and protein produced by the cells was measured for all four components. The frequent finding of t-PA (alone or in combination with u-PA) suggests that t-PA can also be a tumor-associated plasminogen activator. In 11 of the 22 cells PAI-1 mRNA and in 6 of the 22 cells PAI-2 mRNA was found, pointing to a possible role of plasminogen activator inhibitors in the tumor-related plasminogen activator activity. This study demonstrates that there are at least two important regulatory steps in the regulation of production of plasminogen activators and their inhibitors: (a) the regulation at the mRNA level, since a high protein amount is always correlated with a high mRNA amount found in the tumor cells; (b) there must be a significant regulatory step at the (post)translational level as can be concluded from differences in mRNA usage. PMID- 2105840 TI - Light chain variants of an IgG3 anti-GD3 monoclonal antibody and the relationship among avidity, effector functions, tumor targeting, and antitumor activity. AB - R24 is an IgG3 mouse monoclonal antibody which recognizes the ganglioside GD3. Two variants of R24, in which one (V2-R24) or both (V1-R24) light chains were substituted by MOPC-21 light chains, were isolated and characterized. R24 had a 40-fold higher avidity for GD3 than either variant, suggesting that high avidity binding required the presence of two R24 light chains and, thus, divalency. R24 and both variants mediated antibody-dependent cellular cytotoxicity but antibody dependent cellular cytotoxicity mediated by variants was weak compared to R24. The presence of at least one R24 light chain was required for complement dependent cytotoxicity; complement-dependent cytotoxicity was mediated by R24 and weakly by V2-R24 but not by V1-R24. R24, but not V1-R24 or V2-R24, inhibited attachment of melanoma cells to plastic and activated T-lymphocytes, suggesting a threshold of avidity required for these biological effects. In a human melanoma xenograft model in nu/nu mice, radiolabeled R24, variants, and isotype-matched control monoclonal antibodies all appeared to localize in tumors (based on tumor:normal tissue ratios), but specific tumor targeting by R24 was generally 3- to 6-fold higher. R24 prevented melanoma outgrowth in nu/nu mice, while V2-R24 induced partial tumor protection. V1-R24 and the negative control monoclonal antibody did not inhibit tumor outgrowth. Antitumor activity of R24 corresponded to avidity and ability to mediate complement-dependent cytotoxicity in vitro. PMID- 2105841 TI - Selection and preliminary characterization of variant lines of a murine macrophage tumor resistant to the antiproliferative effects of phorbol esters. AB - Treatment of M5076 wild-type cells with 50 ng/ml of 12-O-tetradecanoylphorbol-13 acetate (TPA) almost completely inhibited cellular proliferation. Continuous culture in the presence of TPA was used to derive four lines, one polyclonal (TPAR) and three clonally derived (TPAR-1, -2, and -3), which exhibited variable resistance to the antiproliferative effects of phorbol esters. Protein kinase C (PKC) activation and c-fos expression in wild-type cells and the stably resistant line (TPAR-3) were examined after phorbol ester treatment. Both lines exhibited a comparable rapid and transient induction of c-fos mRNA expression, but induction of c-fos protein was reduced markedly in the TPAR-3 cells. Similarly in both cell lines, prolonged culture in phorbol ester produced down-regulation of PKC, as measured by inducible Mr 80,000 phosphorylation and an in vitro PKC assay. This decrease in PKC levels was paralleled by a decrease in c-fos mRNA and protein induction. Thus, c-fos expression in both wild-type and TPAR-3 cells is a consequence of PKC activation, and the development of resistance to TPA antiproliferative effects in the TPAR-3 cell line was not linked causally to alterations in PKC levels or the c-fos mRNA induction response. The malignant capacity of the TPAR line was not reduced relative to wild-type cells. PKC activation and c-fos mRNA expression do not appear to determine changes in the in vivo or in vitro growth behavior of M5076 cells, whereas variations in c-fos protein expression may determine the anti-proliferative response to tumor promoting phorbol esters. PMID- 2105842 TI - Isolation and characterization of complementary DNA clones corresponding to genes induced in mouse epidermis in vivo by tumor promoters. AB - Complementary DNA clones representing genes in SENCAR mouse epidermis, the expression of which is induced 4 h after one topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) were isolated. Of 56 isolated complementary DNA clones, 32 were identified to be identical to either metallothioneins (MT-I and MT-II) or endogenous retroviral like (VL30) sequences. In situ hybridization and analysis of mRNA levels in cell fractions separated by density gradient centrifugation revealed that MT induction was restricted to keratinocytes in the basal cell layer. Immunohistochemistry and time-kinetic studies on mRNA levels in mouse epidermis showed that the increase in MT and VL30 RNAs coincide in time with a TPA-induced transient block in basal cell proliferation (3-12 h after TPA treatment). MT immunoreactivity and transcript levels had returned to control values at a time point (24 h after treatment) when epidermis is known to hyperproliferate. Treatment with other types of tumor promoters showed that MT-I and MT-II mRNAs were coordinately induced and indicated that sn-1,2-dioctanoylglycerol, 12-O-retinoylphorbol-13-acetate, and mezerein induced MT to a lesser degree than TPA. The calcium ionophore A23187 induced mRNA levels for MTs as well as VL30. VL30 and MT mRNA levels were not found to be elevated in epidermal tumors whereas the mRNA level corresponding to glyceraldehyde-3-phosphate dehydrogenase was elevated in tumors and induced by TPA with time-kinetics that correlate with a TPA-induced hyperproliferation. These complementary DNA clones provide useful tools in the study of the gene regulating effects of TPA in a target tissue relevant for tumor promotion. PMID- 2105843 TI - Disposition of anticancer drugs after bolus arterial administration in a tissue isolated tumor perfusion system. AB - Disposition characteristics of various anticancer drugs in a tissue-isolated tumor preparation were studied in Walker 256 carcinosarcoma-bearing rats using an in situ single-pass vascular perfusion technique. Three anticancer drugs, 5 fluorouracil, mitomycin C, and Adriamycin, and two lipophilic prodrugs of mitomycin C were tested in the tumor preparation perfused with Tyrode's solution containing 4.7% bovine serum albumin. After bolus arterial injection of test drugs, their outflow concentration-time curves were analyzed based on statistical moment theory. In each tumor preparation, the injection of drug was paired with that of vascular reference substance, Evans' blue-labeled bovine serum albumin, and disposition parameters of the drug were corrected with those of vascular reference substance. From the mean transit time values of vascular reference substance, the average vascular volume of the tumor preparation was calculated to be 0.063 ml/g, which decreased with tumor growth. All drugs showed significant extraction by the tumor tissue, depending on their physicochemical properties. Distribution volumes of tested drugs were from 1.53 to 3.33 times larger than the vascular volume. Calculated intrinsic clearance values for the protein-unbound fractions increased as the lipophilicity of the drug increased. The potential increase in tumor uptake was observed in lipophilic prodrugs of mitomycin C. The present experimental system is thus suggested to be useful for analyzing drug disposition in tumor tissue. PMID- 2105844 TI - Re: T. Neil Dear et al., Transcriptional down-regulation of a rat gene, WDNM2, in metastatic DMBA-8 cells. Cancer Res., 49: 5323-5328, 1989. PMID- 2105845 TI - Tumor-infiltrating lymphocytes from nonrenal urological malignancies. AB - Tumor-infiltrating lymphocytes (TIL) were isolated from 15 of 20 surgical specimens of transitional cell carcinoma of the urinary bladder, prostate cancer, testicular cancer, Wilms tumor and adrenal cancer. Expansion was carried out in four different culture conditions, each containing 1000 U/ml interleukin-2: RPMI medium with or without 20% (by volume) of lymphokine-activated killer cell (LAK) supernatant and AIM V medium with or without 20% LAK supernatant. The resultant cell populations were then assayed for cytotoxicity against a variety of autologous and allogeneic tumor targets and phenotypic analysis was performed with fluorescein-labeled monoclonal antibodies. TIL growth was unrelated to the initial percentage of lymphocytes or tumor cells present in the enzymatically dispersed specimens or whether fresh or cryopreserved tissue was utilized. Better growth was seen in AIM V than in RPMI medium (P = 0.013); the beneficial effect of the addition of LAK supernatant to RPMI was indicated (P = 0.065), and the addition of LAK supernatant to AIM V did not improve the ability to culture TIL (P = 0.5) from these cancers. TIL in long-term culture were predominantly CD3+. The ratio of CD4+/CD8+ cells varied with time in culture and culture medium, but most cultures eventually became CD4+. Cells bearing B cell, natural killer cell, and macrophage markers disappeared early in culture. Overall 14/15 TIL samples were lytic against one of the autologous and allogeneic targets tested, but specific lysis against the autologous tumor from which it was derived was seen in only one TIL culture originating from a bladder cancer. Our results suggest that TIL can be expanded to therapeutic levels from a variety of urological malignancies and that their potential role in future therapy should be further explored. PMID- 2105846 TI - Conformational changes involved in the activation of ras p21: implications for related proteins. PMID- 2105847 TI - Functional dissection of Ultrabithorax proteins in D. melanogaster. AB - Expression of Ultrabithorax (UBX) proteins via a heat-inducible promoter generated homeotic transformations of segmental identities in the embryonic cuticle and peripheral nervous system (PNS) of Drosophila and transformed antennae into legs in the adult. The embryonic transformations were used to determine the identity functions of members of the UBX family and UBX mutant forms. Whereas UBX forms I and IV each induced the cuticle transformations, only form I induced the PNS transformations. Analysis of the transformations generated by UBX deletions and by a chimeric Ultrabithorax-Antennapedia protein demonstrated that the majority of the UBX identity information is contained within the C-terminal, homeodomain-containing portion of the protein. Implications of these results for how homeotic proteins select particular metameric identities are discussed. PMID- 2105848 TI - Muramyl dipeptide (MDP) synergizes with interleukin 2 and interleukin 4 to stimulate, respectively, the differentiation and proliferation of B cells. AB - The synthetic immunomodulator muramyldipeptide (MDP) can stimulate B cells. MDP, when used alone, was apparently unable to induce the differentiation or proliferation of resting B cells. In contrast, MDP appeared to synergize with a single recombinant interleukin (IL) to stimulate either their differentiation or proliferation. We used single interleukins to avoid synergistic and antagonistic effects inherent in the use of several factors. IL-2 was found to be sufficient to restore the specific immune response of resting B cells to sheep erythrocytes; MDP greatly increased the number of plaque-forming cells of such IL-2-stimulated B cells. In contrast, IL-4 and interferon-gamma (IFN-gamma), either alone or in the presence of MDP, had no effect in this differentiation assay. MDP was also able to stimulate polyclonally activated B cells. IL-4 increased the proliferation of anti-IgM-stimulated B cells, leading to enlargement and driving more cells into the cell cycle; these effects were further enhanced by MDP, more cells being induced to proliferate, to enlarge, and to progress into the cycle with a higher frequency of cells in the G1B, S, and G2/M compartments. Intracellular free calcium levels were not increased by IL-4 and/or MDP, and the two compounds did not modify the anti-IgM-induced calcium mobilization. Therefore, MDP appears to amplify cytokine effects in B cell activation, by a mechanism which does not appear to involve free calcium mobilization. PMID- 2105849 TI - Activation signals in human lymphocytes: interleukin 2 synthesis and expression of high affinity interleukin 2 receptors require differential signalling for the activation of protein kinase C. AB - The mitogenic activation of resting T lymphocytes involves two distinct cellular events, the synthesis of the ultimate mitogen interleukin 2 and the synthesis and expression of receptors for it. In order to get more detailed information on the mechanisms associated with these activating steps (the effects of different stimuli, leading to activation of protein kinase C were investigated in human lymphocytes). The anti-T-cell receptor (TCR) and anti-CD3 monoclonal antibodies (BMA 031 and BMA 030, respectively), as well as the combination of the phorbol ester, TPA, with a calcium ionophore-induced interleukin 2 synthesis and subsequent proliferation in human peripheral blood lymphocytes. Incubation of cells with synthetic diacylglycerols and calcium ionophores proved to be effective in expression of high affinity interleukin receptors, no detectable amounts of interleukin 2 were, however, synthetized. When diacylglycerols were, however, added repetitively, interleukin 2 was also produced. Both anti-TCR/CD3 antibodies and TPA or DiC8 caused activation and translocation of protein kinase C from the cytosol to the plasma membrane. Significant differences, however, were observed between the time kinetics of the translocation of the enzyme. In plasma membranes of TPA-stimulated cells activation of protein kinase C was detectable up to 4 hr. In contrast, the highest specific activity of protein kinase C was measured in the plasma membranes after 15 min of DiC8 addition to cells. Anti-CD3 monoclonal antibodies activated protein kinase C in a biphasic manner. Shortly after binding of BMA 030 to the T cell antigen receptor/CD3 complex the activity of protein kinase C was increased in the plasma membrane, then it declined to control levels followed by a second long-lasting activation of the enzyme up to 4 hr. These results suggest different signal requirements for different activation steps. While for synthesis and expression of interleukin 2 receptors a short term activation of protein kinase C is sufficient, long-term activation of the enzyme is necessary for interleukin 2 synthesis in human lymphocytes. PMID- 2105850 TI - Selection of CD4+CD8+ thymocytes by complex formation with medulla-derived epithelial cells. AB - The role of lymphostromal complexes in T-cell differentiation is far from elucidated, mainly because a clear association of a particular stromal cell type with a distinct thymocyte subset has never been identified. Using an in vitro system, detecting the adherence of thymocytes to a thymic medullary epithelial cell line (E-5), we showed that the phenotype of these thymocytes was that of cortical type: Thy-1hi, LFA-1+, PNAhi, CD4+CD8+, MEL-14-/lo, IL-2R-, CD3-/lo, and TcR V beta 8-/lo. They were enriched in cells in G2/M at the time of complex formation, showed a higher basal proliferation in culture, and did not respond to PHA, IL-2 and only marginally to Con A. These data show that complex formation with mouse thymic medullary epithelium selects for CD4+CD8+ thymocytes, as shown by the marked decrease in CD4+CD8-/CD4-CD8+ thymocytes, and the incapacity of CD4 CD8- thymocytes to adhere. PMID- 2105851 TI - Macrophage-dependent stimulation of T cell-depleted spleen cells by Clostridium difficile toxin A and calcium ionophore. AB - Clostridium difficile toxin A causes severe intestinal inflammation and fluid secretion in rabbit ileum and is chemotactic for neutrophils in vitro. The mechanism of intestinal injury produced by toxin A appears to involve direct epithelial cell damage as well as recruitment of an inflammatory cell response. The current study was undertaken to determine if toxin A can directly stimulate a proliferative response in lymphocytes. Highly purified toxin A, in the presence of the calcium ionophore, ionomycin, stimulated substantial [3H]thymidine incorporation by murine splenic lymphocytes, which was maximal at 10(-9) M toxin A and 800 ng/ml ionomycin. Removal of T cells with anti-Thy-1.2 antibody plus complement had no effect on the proliferative response induced by toxin A. However, [3H]thymidine incorporation in response to toxin A was significantly inhibited (P less than 0.001) by the removal of macrophages from splenocyte suspensions and was restored by the addition of peritoneal macrophages or cell free supernatant from toxin A-treated macrophage cultures. Analysis of the toxin A-treated macrophage supernatants showed high levels of IL-1, but not IL-2 or IL 4. The combination of recombinant IL-1 plus ionomycin was found to stimulate [3H]thymidine incorporation by T cell-depleted splenic lymphocytes. These results suggest that toxin A stimulates the release of IL-1, and possibly other factors, from macrophages which can costimulate murine B lymphocytes. PMID- 2105852 TI - STB1, a mouse lymphocyte marker found on T cell and B cell subpopulations. AB - A set of monoclonal antibodies has been raised to cell surface markers which are either hyperexpressed, or exclusive to activated murine lymphocytes. One antigen is present on all B cells of the Ly1 lineage and defines a novel subpopulation of classical B cells, most of which are activated B cells. In Western blots, this antigen appears as a single glycoprotein of 95 kDa molecular weight but of greater interest, is its expression at high levels on all mature peripheral T cells but on only 30% of thymocytes. This marker is expressed at high levels on all CD4 and CD8 thymocytes, most double-negative (CD4-CD8-) thymocytes, and at low levels on double-positive (CD4+CD8+) thymocytes. It may prove useful as a developmental marker for subdividing the double-positive (CD4+CD8+) and double negative (CD4-CD8-) thymocyte populations. Taken together these results indicate that mab 3.17 recognises a novel lymphocyte antigen expressed on subsets of T and B cells, which is hyperexpressed on lymphocyte activation. PMID- 2105853 TI - Activation of human CD8-positive T cells via the CD8/HLA class I complex. AB - Cross-linking of CD8 and HLA class I molecules with appropriate monoclonal antibodies (mAb) and goat anti-mouse Ig (GaMIg) antibody resulted in a marked proliferation of resting human CD8 cells in the presence of interleukin-2 (IL-2). These cells also expressed IL-2 receptor (IL-2R), transferrin receptor, HLA-DR and -DQ antigens. Activation of the cross-linked CD8 cells is apparently independent of accessory monocytes. Various anti-CD8 and anti-HLA class I mAb recognizing nonpolymorphic antigenic determinants were examined for the efficacy of activating CD8 cells. Among mAb specific for HLA class I molecules, PA2.6, MB40.5, BB7.7, A1.4, and W6/32 mAb markedly stimulated the proliferation of cross linked CD8 cells, whereas BBM.1, Q1/28, and HC10 mAb were found inactive. Footprinting analysis of HLA class I molecules suggested that the activity of these anti-HLA class I mAb appeared to be related to the corresponding peptides they protect from enzymatic digestion. In contrast to the anti-HLA class I mAb, all anti-CD8 mAb examined (C8, OKT8A, and anti-Leu-2a) induced the proliferation of CD8-HLA class I cross-linked cells with similar efficacy. These results suggest that physical interaction between CD8 and at least one specific region of HLA class I molecules can trigger the activation of resting human CD8 cells. PMID- 2105854 TI - IL-2, IL-6, and IFN-gamma have distinct effects on the IL-4 plus PMA-induced proliferation of thymocyte subpopulations. AB - We have previously reported complex effects of cytokine-containing T cell supernatants on the interleukin (IL)4 plus phorbol 12-myristate 13-acetate (PMA) induced proliferative response of murine thymocytes. Here we show that recombinant murine IL-2, IL-6, and IFN-gamma each differentially regulate the IL 4/PMA-driven growth of thymocyte subpopulations. Thymocytes fractionated into four subpopulations on the basis of CD4 and CD8 expression were stimulated to proliferate by IL-4/PMA. Interferon-gamma (IFN-gamma) caused almost complete inhibition of the CD4+/CD8- response but had no measurable effect on the growth of CD4-/CD8+ or CD4-/CD8- populations. This inhibitory effect was also observed on splenic CD4+/CD8- T cells. In contrast, IL-6 strongly enhanced the proliferative response of CD4+/CD8- thymocytes, but showed no effect on peripheral CD4+/CD8- T cells, suggesting that IL-6 may be an important regulator of growth in the thymus. IL-2 also enhanced the proliferation of both CD4-/CD8+ and CD4-/CD8- thymocytes to IL-4 and PMA. To test whether the IL-4/PMA stimulus provided all the signals required to initiate growth in each subpopulation, we titrated cell number and examined the relationship between cell dose and cell response. Growth of CD8+/CD4- cells was cell density independent, indicating that IL-4/PMA is sufficient stimulus to induce growth of these cells. In contrast, growth of CD4-/CD8- and CD4+/CD8- cells is cell density dependent, suggesting a requirement for another signal provided by the cells themselves. These observations suggest that more signals remain to be identified in this thymocyte growth system. PMID- 2105855 TI - Effect of superoxide dismutase on the autoxidation of substituted hydro- and semi naphthoquinones. AB - The effect of superoxide dismutase on the autoxidation of hydro- and semi-1,4 naphthoquinones with different substitution pattern and covering a one-electron reduction potential range from -95 to -415 mV was examined. The naphthoquinone derivatives were reduced via one or two electrons by purified NADPH-cytochrome P 450 reductase or DT-diaphorase, respectively. Superoxide dismutase did not alter or slightly enhance the initial rates of enzymic reduction, whereas it affected in a different manner the following autoxidation of the semi- and hydroquinones formed. Autoxidation was assessed as NADPH oxidation in excess to the amounts required to reduce the quinone present, H2O2 formation, and the redox state of the quinones. Superoxide dismutase enhanced 2--8-fold the autoxidation of 1,4 naphthosemiquinones, following the reduction of the oxidized counterpart by NADPH cytochrome P-450 reductase, except for the glutathionyl-substituted naphthosemiquinones, whose autoxidation was not affected by superoxide dismutase. Superoxide dismutase exerted two distinct effects on the autoxidation of naphthohydroquinones formed during DT-diaphorase catalysis: on the one hand, it enhanced slightly the autoxidation of 1,4-naphthohydroquinones with a hydroxyl substituent in the benzene ring: 5-hydroxy-1,4-naphthoquinone and the corresponding derivatives with methyl- and/or glutathionyl substituents at C2 and C3, respectively. On the other hand, superoxide dismutase inhibited the autoxidation of naphthohydroquinones that were either unsubstituted or with glutathionyl-, methyl-, methoxyl-, hydroxyl substituents (the latter in the quinoid ring). The inhibition of hydroquinone autoxidation was reflected as a decrease of NADPH oxidation, suppression of H2O2 production, and accumulation of the reduced form of the quinone. The enhancement of autoxidation of 1,4 naphthosemiquinones by superoxide dismutase has been previously rationalized in terms of the rapid removal of O2-. by the enzyme from the equilibrium of the autoxidation reaction (Q2-. + O2----Q + O2-.), thus displacing it towards the right. The superoxide dismutase-dependent inhibition of H2O2 formation as well as NADPH oxidation during the autoxidation of naphthohydroquinones--except those with a hydroxyl substituent in the benzene ring--seems to apply to those organic substrates which can break down with simultaneous formation of a semiquinone and O2-.. Inhibition of hydroquinone autoxidation by superoxide dismutase can be interpreted in terms of suppression by the enzyme of O2-.- dependent chain reactions or a direct catalytic interaction with the enzyme that might involve reduction of the semiquinone at expense of O2(-.).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2105856 TI - Multiple DNA adducts in lymphocytes of smokers and nonsmokers determined by 32P postlabeling analysis. AB - Identification of DNA adducts in peripheral lymphocytes could serve as a means of monitoring human exposure to potential genotoxic agents. In this study, DNA from peripheral lymphocytes of smokers and nonsmokers was examined for adducts by the P1 nuclease 32P-postlabeling technique. Thin layer chromatography (TLC) maps from both groups revealed multiple DNA adducts which ranged from no adducts for one individual to six adducts for a different individual. The total DNA adduct concentrations were approximately one adduct in 10(8)-10(10) normal nucleotides. Comparison of the adduct TLC profiles revealed individual variation in both pattern and level of DNA adducts. The type and amount of adduct was not influenced by smoking history and remained unchanged in four out of six subjects who were resampled after a 1 month interval. The capacity of lymphocytes to form BaP-derived DNA adducts after a 72 h incubation with 10(-6) M [3H]BaP was measured by both high-performance liquid chromatography (HPLC) and 32P postlabeling analysis. The in vitro adduct values detected by [3H]nucleoside concentrations on HPLC ranged from 1 to 7 fmol adduct per micrograms DNA (3.3 23.3 adducts per 10(7) nucleotides). The [3H]nucleoside values were consistent with values obtained by 32P-postlabeling of the same sample (correlation coefficient of 0.88). No relationship was apparent between the capacity of lymphocytes to form a [3H]BaP-derived adduct in vitro and the concentration of any adduct, or total adducts present in untreated lymphocytes. These results suggest that multiple DNA adducts are present in lymphocytes from nonsmokers as well as smokers, although the profile and extent of these adducts can vary among individuals. The relationship of the lymphocyte DNA adducts detected in this study to human cancer susceptibility remains to be determined. PMID- 2105857 TI - A unitized enzyme-labeled immunometric digoxin assay suitable for rapid testing. AB - An enzyme-labeled immunometric assay has been developed for measuring digoxin concentrations in serum or plasma. Unitized, compartmentalized reagents are used with an automated sample-processing instrument. The enzyme activity of the processed sample, which is directly proportional to the digoxin concentration, is measured by using a reagent strip and the Ames Seralyzer reflectance photometer. The test takes less than 15 min, and digoxin concentrations are calculated from a two-point calibration line stored in the instrument. Within-run CVs for controls at four concentrations ranged from 2.3% to 3.8%; between-run CVs were from 1.5% to 2.6%. Results obtained with clinical serum samples correlated well (r greater than 0.96) with those obtained by fluorescent polarization immunoassay (Abbott TDx) and RIA (Clinical Assays and NML). This rapid and convenient method for monitoring digoxin concentrations in serum or plasma is particularly well suited for decentralized sites such as emergency rooms, urgent-care centers, and physicians' offices. PMID- 2105858 TI - Variation in concentration of lipids, lipoprotein lipids, and apolipoproteins A-I and B in plasma from healthy women. AB - The components of total variation--biological, inter- and intra-individual, and analytical--of plasma lipids, lipoprotein lipids, and apolipoproteins A-I and B have been determined in a population of 44 healthy women, ages 18-35 years. Blood was sampled three separate times at three-month intervals, with no restrictions on diet or physical activity during these periods. The greatest inter-individual variances were observed for high-density lipoprotein (HDL)-cholesterol, HDL2 cholesterol, and total plasma cholesterol. Triglycerides had the highest intra individual variance (CV 22%). The percentage of inter- and intra-individual variances of apolipoprotein A-I concentrations were more reflective of total HDL- and HDL2-cholesterol content than of HDL3-cholesterol. Concentrations of calculated low-density-lipoprotein cholesterol showed a greater inter-individual variation (18.6%) than did apolipoprotein B (10.7%). The laboratory CVs for these analytes were similar to other reported values. From these data, we computed the expected variation for subjects in our study for single and repeated measurements. Such considerations can influence decision-making in the clinical setting or in designing epidemiological studies. PMID- 2105859 TI - Effects of analytical method and lyophilized sera on measurements of apolipoproteins A-I and B: an international survey. AB - In 1987 a collaborative study was initiated with 140 laboratories worldwide to evaluate the effects of analytical method and lyophilization on the measurement of different concentrations of apolipoproteins (apo) A-I and B in four lyophilized serum pool samples. This survey confirmed that the lyophilized apo Reference Material of the International Union of Immunological Societies (IUIS) is useful for apo A-I assays as an international serum-based reference material, because among-method variation is negligible. The apo A-I concentration value of 1.24 g/L is now assigned to the IUIS Reference Material (CDC 1883) by a Centers for Disease Control RIA in-house reference method. Use of lyophilized serum preparation as a reference material for some modes of apo B measurement is questionable because of lyophilization and matrix effects. Both radial immunodiffusion and liquid immunoprecipitin methods demonstrated bias in measured apo B concentrations, compared with overall method-weighted means values on the IUIS Reference Material. Because of the uncertainty associated with LDL primary standard, protein analysis, and concentration differences among analytical methods, assigning a single apo B concentration value to the IUIS Reference Material appears inadvisable at present. PMID- 2105860 TI - Effect of stripping thyroxin from thyroxin-binding globulin on the measurement of free thyroxin in serum by equilibrium dialysis and by radioimmunoassay. AB - In considering factors that might influence measurement of free thyroxin (T4), we evaluated the proportion (%) of T4 that could be stripped from thyroxin-binding globulin (TBG). The percentage of free T4 was measured in serially diluted sera from four normal subjects, four patients with hyperthyroidism or hypothyroidism, four pregnant women, and four malnourished subjects with low TBG. The critical percentage of stripping was determined by the product of the percentage free T4 and the critical dilution factor (the point where the percentage free T4 began to decrease). The mean values obtained for the respective patient groups--6.38%, 2.76%, 16.73%, 9.75%, and 4.28%--were proved to be related to the rate of saturation of TBG with T4. Values for percentage stripping determined with the "GammaCoat two-step RIA" and the "LiquiSol RIA" were well within the critical percentage stripping by equilibrium dialysis, except in the case of low-TBG serum as measured by LiquiSol RIA. Free T4 concentration as measured by LiquiSol RIA decreased as sample volume decreased. These findings were ascribed to the relatively high values for percentage stripping in the LiquiSol RIA, which led to erroneously low values for free T4. PMID- 2105861 TI - "Microgel diffusion blotting" for sensitive detection of antibodies to extractable nuclear antigens. AB - A fast immunoblotting procedure, termed "microgel diffusion blotting," is used to detect and identify antibodies to extractable nuclear antigens (i.e., to Sm, RNP, and SSB) in patients with rheumatic diseases. The method differs from the standard immunoblotting techniques by the use of ultra-thin microgels for polyacrylamide gel electrophoresis: the very thin gel layer allows transfer of proteins to a nitrocellulose membrane by simple diffusion. Principal advantages of this variant technique are its simplicity, rapidity, and reproducibility- characteristics that make the test suitable for routine application. We compared the sensitivity of the test with that of double immunodiffusion in agarose for the evaluation of humoral antinuclear immunity. Microgel diffusion blotting detected antibodies in serum at concentrations less than 0.001 of those detectable by immunodiffusion. PMID- 2105862 TI - Validation of highly specific and sensitive radioimmunoassays for lutropin, follitropin, and free alpha subunit in unextracted urine. AB - Measurement of the urinary excretion of lutropin (LH) and follitropin (FSH) and their common free alpha subunit (FAS) assists in monitoring the maturation of the hypothalamic-pituitary-gonadal axis and in understanding the physiology of the pituitary glycoprotein hormones. Here we describe sensitive, specific polyclonal radioimmunoassays for LH and FSH and a monoclonal radioimmunoassay for FAS for use with urine--assays unperturbed by alterations in urinary pH or osmolarity within the broad physiological range encountered in urine. Concordance between LH, FSH, and FAS concentrations in extracted and unextracted urine samples was high. Linearity and parallelism with the standard curves was observed with addition of 25 to 200 microL of unextracted urine. No effect on glycoprotein concentration was seen after as many as 10 freeze-thaw cycles. The need for extraction was further obviated by the high sensitivity of each assay, reflected by minimum detectable doses well below the concentrations encountered in patients' samples. Thus we have measured gonadotropins in unextracted urine as precisely as in extracted urine. We also have demonstrated an equally versatile assay for urinary alpha subunit, using a monoclonal antibody of high specificity for this monomer in its free, uncombined form. These radioimmunoassays complement assays of gonadotropins and free alpha subunit in serum and will allow longitudinal investigations otherwise limited by the constraints of the patient's blood volume. PMID- 2105863 TI - Effects of lyophilization of serum on the measurement of apolipoproteins A-I and B. AB - A common accuracy-based standardization program is indispensable for establishing reference intervals for the clinical use of apolipoproteins. The development and distribution of reference materials and quality-control materials that do not exhibit matrix effects between methods is essential to the standardization process. We examined the suitability of lyophilized material as a common reference material for the measurement of apolipoproteins A-I and B. We determined values for apolipoproteins A-I and B in frozen and lyophilized serum pools, using different immunochemical approaches. We found little or no differences in apolipoprotein A-I values between frozen and lyophilized pools as determined by the different methods. In contrast, values for apolipoprotein B in lyophilized samples were consistently lower than those obtained for frozen samples. After adjusting for the effect of dilution due to reconstitution, the difference in the apolipoprotein B values for lyophilized as compared with frozen samples ranged from -26% to 4%, depending upon the assay method. Evidently, serum pools in lyophilized from are not a suitable matrix for reference materials for apolipoprotein B measurements but can be used for apolipoprotein A-I measurements. PMID- 2105864 TI - Valproic acid-associated pancreatitis: report of three cases and a brief review. AB - We describe three patients with seizure disorders in whom pancreatitis or pancreatic injury was probably caused by valproic acid, a widely used anticonvulsant drug. Trivial or no increases of serum amylase (EC 3.2.1.1) but striking increases of serum lipase (EC 3.1.1.3) were common to all patients, as assayed in the Kodak Ektachem. In vitro, valproic acid does not cause any change in serum lipase. In patients with symptoms suggestive of pancreatitis and abnormal values for amylase and (or) lipase, treatment with valproic acid should be discontinued. PMID- 2105865 TI - Antibodies against light chains in immunoglobulin class-specific antisera. PMID- 2105866 TI - Unexplained osmolal gap in diabetic ketoacidosis (not due to acetone) PMID- 2105867 TI - Possible overestimation of ultracentrifugally isolated "free" apoprotein A-I in serum. PMID- 2105868 TI - Defective interleukin-2 induction of lymphokine-activated killer (LAK) activity in peripheral blood T lymphocytes of patients with monoclonal gammopathies. AB - The recombinant interleukin-2 (rIL-2) generation of lymphokine-activated killer (LAK) cells was investigated in peripheral blood T lymphocytes (PBT) of 16 patients with monoclonal gammopathy of undetermined significance (MGUS) and 32 patients with multiple myeloma (MM). LAK activity was significantly decreased in MM, but not in MGUS patients, and was partially recovered in MM in the remission phase. This finding was unexpected, because CD8+ CD11b+ cells, which contain LAK precursors, are significantly increased in MM. LAK activity was investigated in purified CD8+ CD11b+ lymphocytes to discriminate between an intrinsic defect or a defective regulation by other T cell subsets. These cells were intrinsically unable to generate LAK activity fully following rIL-2 stimulation. MM showed the more pronounced LAK deficiency, while MGUS patients showed intermediate values. Phenotyping revealed significantly increased proportions of Leu7+ and HLA-DR+ cells in MM patients. These data reveal another dysregulation of T cell effector functions in patients with monoclonal gammopathies and offer further evidence of the impairment of their cell-mediated immunity. PMID- 2105869 TI - Heterotopic bone formation after noncemented total hip arthroplasty. Location of ectopic bone and the influence of postoperative antiinflammatory treatment. AB - The regional-development of heterotopic bone around the hip and the influence of postoperative prophylaxis with antiinflammatory drugs were studied in 66 patients treated with 74 noncemented, porous-coated total hip arthroplasties (THA) using the McFarland approach. Thirty patients (34 hips) were treated with antiinflammatory drugs during the early postoperative period. Heterotopic bone developed in two different regions: central, around the neck of the femoral component, and lateral to the greater trochanter of the femur. Central ossifications were recorded in 53% of the hips and appeared significantly less frequently in patients postoperatively treated with antiinflammatory drugs. Lateral ossifications were recorded in 71% of the hips, and no significant prophylactic effect was found for postoperative antiinflammatory treatment. In response to the McFarland approach in THA, heterotopic ossifications may appear both centrally around the neck of the femoral component and lateral to the trochanter in the substance of the medial gluteal muscle. The latter may be comparable to post-traumatic myositis ossificans. PMID- 2105870 TI - CO2 arthroscopy of the knee. AB - During the past ten years, approximately 3000 cases of knee arthroscopy have been performed in a CO2 medium. The setup for the use of CO2 is quite simple and is explained here on a step-by-step basis. Advantages are a better visual field and no motion of tissue in the arthroscopic field. The disadvantages are minimal. For these reasons, it is believed that CO2 arthroscopy is a significant adjunct to arthroscopy in a fluid medium. PMID- 2105871 TI - Insertion site complications during the first year of NORPLANT use. AB - Although review articles have provided much information on the NORPLANT system, information on insertion site complications based on multi-country trials has been limited to infection rates. This paper examines 2,674 NORPLANT acceptors from seven countries who were enrolled and followed for one year. The one-year incidence rates of infection (0.8%), expulsion (0.4%) and local reaction (4.7%) varied widely among countries and clinics within a country. In contrast to previous reports that insertion site complications occur during the first few weeks of use, these data show that a substantial proportion of insertion site infections (34.6%) and implant expulsions (64.3%) were reported after the first two months of use, while 35.7% of local reactions were reported after 4.5 months of use. Of the 16 women with infections who did not have the implants immediately removed, 8 eventually required or requested removal, indicating that the ICCR recommendation for immediate removal in case of infection appears appropriate. An awareness of the frequency of insertion site complications, distribution of the time of onset post-insertion and potential sequelae of complications will aid clinicians in better client counseling and complication management. PMID- 2105872 TI - Pharmacokinetic comparison of two triphasic oral contraceptive formulations containing levonorgestrel and ethinylestradiol. AB - The pharmacokinetics of levonorgestrel (LNG) and ethinylestradiol (EE2) were determined in 24 women (aged 21 to 35 years), following the administration of a single tablet from the second phase of two different triphasic preparations (Triphasil and Trinordiol. Each tablet contained 0.075 mg of LNG and 0.040 mg of EE2. The data were compared to the pharmacokinetics of LNG and EE2 obtained following the oral administration of a hydroalcoholic solution (standard) containing the same steroids and dose. The study consisted of a randomized design in which the three formulations were administered to each of the 24 subjects in a three-period crossover pattern. Blood samples were taken at frequent intervals after dosing. Serum levels of LNG and EE2 were measured by specific radioimmunoassays. The results show that both LNG and EE2 in the Triphasil and Trinordiol tablets are bioequivalent with respect to rate and extent of absorption. Furthermore, LNG, but not EE2, in both tablet formulations was bioequivalent to the solution dose. The serum concentration-time profiles for the three formulations showed that the range of mean peak levels was 2.3-2.8 ng/ml for LNG and 116-159 pg/ml for EE2. These levels were achieved within 2 hours in the majority of subjects. The ranges of mean values calculated for the areas under the curves were 15-16 ng.hr/ml for LNG and 1053-1390 pg.hr/ml for EE2. The ranges of mean values calculated for other pharmacokinetic parameters were: volume of distribution: LNG--1.6-1.8 L/kg, EE2--7.7-9.1 L/kg; clearance: LNG--84 88 ml/hr/kg, EE2--0.67-0.99 ml/hr/kg; half-life: LNG--13-15 hr, EE2--7-12 hrs. PMID- 2105873 TI - Inhibitory effects of treatment with an LHRH antagonist on the ovulatory cycle are reduced when administered during the late follicular phase. AB - To compare the effects of transitory suppression of pituitary gonadotropin secretion by an LHRH antagonist at the mid or late follicular phase of the menstrual cycle, adult macaques with normal menstrual cycles were treated with an LHRH antagonist (N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10 ]LHRH (detirelix) administered subcutaneously at a dose of 300 micrograms/kg, daily for 3 days beginning either during the mid or late follicular phase. In all eight animals treated during the mid follicular phase, serum concentrations of LH and FSH declined and remained suppressed for 4 days. This caused a fall in serum concentrations of estradiol and the expected ovulation failed to occur. During the recovery period a marked rise in serum FSH occurred followed by normal follicular development and ovulation 14.8 +/- 0.6 days after the last injection of antagonist. Of the 9 macaques given the same treatment during the late follicular phase, only in two was the expected rise in serum progesterone prevented. In 4 of the animals a transitory suppression in LH and estradiol was observed but this was followed by a recovery and occurrence of an LH surge and rise in serum progesterone indicating ovulation during the course of treatment. In the remaining 3 macaques treatment commenced on the day of the initiation of the LH surge and was associated with a progesterone rise of normal duration but lower than normal magnitude during the early luteal phase. These results show that LHRH antagonist treatment causes rapid inhibition of pituitary-ovarian function when administered up to the mid follicular phase of the cycle and is effective in blocking ovulation. The suppressive effects of the antagonist are reduced when administered during the late follicular phase. This may be due to decreased dependence of the pituitary gonadotrope on LHRH at this time and on decreased dependence of the dominant follicle on the gonadotropins. PMID- 2105874 TI - Intravenous midazolam suppression of pentylenetetrazol-induced epileptogenic activity in a porcine model. AB - Generalized tonic-clonic seizures are a neurologic emergency. Duration of ictal activity has been associated with neurologic sequelae. The purpose of this study was to determine if midazolam, a short-acting benzodiazepine, could effectively ablate ictal activity in an animal model without significant cardiorespiratory compromise. Ten domestic swine (10 to 20 kg) were ventilated and hemodynamically monitored. Bifrontal craniotomies were performed and electrocortical activity was recorded throughout the experiment. Pentylenetetrazol (100 mg/kg) was administered iv to induce seizures. Midazolam (0.1 mg/kg) was administered iv and serum levels were drawn at 1, 2, 5, 10, 15, and 20 min after administration. There was no significant difference between the baseline and postmidazolam vital signs. Seizure activity was seen periodically as generalized spikes, as well as individual spikes for 29 +/- 5 sec after midazolam administration. A period of attenuation of 24 +/- 7 sec was seen before returning to baseline electrocortical activity. Our study demonstrates that midazolam effectively ablated induced ictal activity without significant cardiorespiratory depression and with similar EEG effect as other benzodiazepines. PMID- 2105875 TI - Review of the rapid normalization of serum albumin with modified total parenteral nutrition solutions. AB - The theoretical basis for the rapid normalization of hypoalbuminemia is contingent on recognition of those clinical circumstances requiring rapid and prolonged repair of colloid oncotic pressure. Standard total parenteral nutrition (TPN) solutions repair serum protein only after prolonged periods of therapy. Nutritionists have empirically observed that adding albumin to TPN solutions can quickly normalize hypoalbuminemia for sustained periods. Infusion of similar quantities of albumin without TPN results in no prolonged normalization. The mechanism of the rapid normalization of serum albumin with albumin-modified TPN solutions has yet to be determined, as has its relationships to prevention of hypoalbuminemia-associated morbidity and mortality. PMID- 2105876 TI - Role of leukotrienes in hydrochloric acid-induced gastric lesions in rats. AB - This study was designed to clarify the role of leukotrienes (LTs) in 0.6 N hydrochloric acid (HCl)-induced gastric lesions. In rats given 1 ml of 0.6 N HCl intragastrically, severe hemorrhagic lesions were observed in the gastric corpus mucosa 15 min, and 1, 3, and 5 hr after HCl administration. In the control rats treated with physiological saline, LTs in gastric mucosa were not observed throughout the experiments. Peptide LT contents (sum of LTC4 and LTD4) after 1 or 3 hr were increased to 13.2 +/- 2.9 ng/g tissue and 6.3 +/- 1.9, respectively, although peptide-LTs were not observed 15 min and 5 hr after HCl administration. Premedication with AA-861, a lipoxygenase inhibitor, decreased dose-dependently peptide LT contents 1 hr after HCl administration. Furthermore, gastric lesions caused by 0.6 N HCl were significantly prevented by 300 mg/kg of AA-861 3 hr after HCl administration, although the dose of AA-861 did not significantly prevent gastric lesions 1 hr after HCl administration. Administration of YM-638, a peptide LT antagonist, showed similar protective effects to AA-861 except inhibition of increase in LT levels after HCl administration. These results suggest that peptide LTs contribute to persistence of gastric lesions, although they might not participate in the onset of 0.6 N HCl-induced gastric lesions. PMID- 2105877 TI - Treatment of biliary colic and acute cholecystitis with prostaglandin synthetase inhibitors. PMID- 2105878 TI - [Life-threatening lactic acidosis during total parenteral nutrition. Successful therapy with thiamine]. AB - Two patients, 37 and 44 years old, respectively, developed severe metabolic acidosis after abdominal surgery which was followed by three weeks of total parenteral nutrition. Septicaemia, peritonitis or hypoxia were excluded as possible causes. Both patients had very high serum lactate concentrations (24.3 and 22.8 mmol/l, respectively). Conventional treatment with buffer agents was unsuccessful. Because vitamin B1 deficiency was suspected, two doses of 400 mg thiamine were administered. In both patients the extreme lactic acidosis disappeared immediately after the injections. Both patients were later discharged without any symptoms. PMID- 2105879 TI - [Systemic lysotherapy using recombinant tissue plasminogen activator for fulminant pulmonary embolism]. AB - A 44-year-old woman sustained massive pulmonary embolization from a deep leg-vein thrombosis. She was given 70 mg recombinant tissue plasminogen activator (rt-PA) by continuous intravenous drip over two hours. Before this treatment perfusion scintigraphy had demonstrated complete absence of flow in the right lung due to embolic occlusion of the central hilar vessels. In addition there were several segmental filling defects in the left lung. Even during the two-hour infusion the circulatory state began to improve, as did echo- and electrocardiographic signs of acute right heart strain. Correspondingly there was a rapid raise in arterial pO2. Another scintigraphy after 48 hours revealed almost complete reperfusion of the right lung and the left lung segments. This case demonstrates that infusion of rt-PA can be an effective and relatively risk-free method of treating haemodynamically significant massive lung embolism, even in comparison with selective or systemic thrombolysis with urokinase or streptase or with surgical embolectomy. PMID- 2105880 TI - Long-term effects of continual intake of phenobarbital on the spontaneously epileptic rat. AB - Spontaneously epileptic rats (SER) are a double mutant (zi/zi, tm/tm) spontaneously exhibiting both tonic and absence-like seizures. We examined the long-term effects of continual intake of phenobarbital (PB) on SER as a method of assessing long-term evaluation of antiepileptic drugs (AEDs). Food pellets containing 0.1% PB were given ad libitum from 7 weeks of age. Plasma PB level was maintained at 30-70 micrograms/ml after age 11 weeks. Tonic seizures were inhibited markedly in rats that received PB until age 15-16 weeks, but thereafter the inhibitory effects of PB gradually decreased. An increase of body weight and prolongation of survival were also noted in SER that received PB. Cortical and hippocampal EEG of SER were recorded with chronically implanted electrodes from 11 weeks of age pre-PB and 3, 7, and 14 days post-PB intake. These animals exhibit absence-like seizures characterized by sudden appearance of 5-7-Hz spike wave-like complexes on EEG concomitant with immobility and staring. The seizures were not affected until age 13 weeks (2 weeks after intake of PB), although tonic seizures were inhibited. SER are considered a useful model for evaluating the long-term effects of AEDs. PMID- 2105881 TI - Multidisciplinary analysis of patients with extratemporal complex partial seizures. I. Intertest agreement. AB - In 15 patients we hypothesized the origin of epilepsies to be 'extratemporal' based on videotaped seizures and surface EEG. Neuropsychological tests and neuroimaging (CAT, MRI, and PET scans) were then compared to the hypothesized ictal sites. Neuropsychological tests were abnormal in 86.6% and FDG-PET scans were abnormal in 73%. The neuropsychological tests and PET localized or lateralized areas of dysfunction to the same sites as electroclinical characteristics did in 85% of patients (P less than 0.01, Fisher exact test). No statistically significant correlation between lesion sites on CT and MRI and the ictal origin was observed due to the high proportion of normal or non-specific scans. These observations should be verified in a larger series of extratemporal seizures. PMID- 2105882 TI - Eight small subunits of Euglena ribulose 1-5 bisphosphate carboxylase/oxygenase are translated from a large mRNA as a polyprotein. AB - The small subunit (SSU) of ribulose 1-5 bisphosphate carboxylase/oxygenase is a 15 kd protein in Euglena gracilis. The protein is synthesized as a 130 kd precursor as shown by immunoprecipitation of in vitro translation products and confirmed by immunoprecipitation of in vivo pulse-labeled Euglena proteins. From the published SSU amino acid sequence, an oligonucleotide was synthesized that specifically hybridizes to a large mRNA whose length (approximately 4.3 kb) is consistent with the precursor size. The complete nucleotide sequence of the SSU mRNA was obtained by sequencing a cDNA clone from a lambda gt11 library and completed by direct mRNA sequencing. We report for the first time the complete sequence of a large mRNA and show that it encodes eight consecutive SSU mature molecules. The deduced precursor amino acid sequence shows that the amino terminus of the first SSU molecule is preceded by a 134 amino acid peptide which is cleaved during the maturation process. This long transit peptide exhibits features characteristic of signal peptides involved in the secretion of proteins through the endoplasmic reticulum. This is in agreement with the idea that the third (outer) membrane of the Euglena chloroplast envelope is of endoplasmic reticulum origin. PMID- 2105883 TI - Structural features of the cytoplasmic region of CD4 required for internalization. AB - CD4, the T cell surface antigen, is phosphorylated and internalized when T cells are activated or treated with a phorbol ester, PMA. The actual phosphorylation sites have been identified and the role of phosphorylation of each on CD4 internalization investigated. Seven different mutants, in each of which one, two or all three of the serine residues of the cytoplasmic region was modified to alanine(s) (CD4.SA mutants) and one mutant in which the whole amino acid sequence from Gln421 to the C-terminal Ile433 was changed (CD4.EP mutant) were constructed and used to determine the effect of phosphorylation on CD4 internalization. Ser408 was the most efficiently phosphorylated by PMA treatment, Ser415 next and Ser431 to a minor extent. The effect of mutation on internalization was well matched with the effect on extent of phosphorylation, i.e. Ser408 was the residue most important for internalization. However, complete inhibition of CD4 internalization was achieved only by mutating all three serine residues. Interestingly, the mutant CD4.EP in which Ser408 was present and phosphorylated was not measurably internalized, suggesting that phosphorylation of Ser408 induces CD4 internalization only when other structural features of the cytoplasmic domain remain intact. In addition, the data suggest the existence of an additional minor pathway for CD4 internalization which is phosphorylation independent. PMID- 2105884 TI - Murine lambda gene rearrangements: the stochastic model prevails over the ordered model. AB - The ontogeny of the immunoglobulin (Ig) gene rearrangement in mammalian B cells seems to be ordered. Heavy chain gene segments rearrange first, followed by light chain gene segments, kappa before lambda. The genomic organization of murine lambda locus does not preclude the simultaneous expression of two subtypes from the same chromosome. In order to distinguish between an ordered and a stochastic model of rearrangement, a panel of 67 B cell hybridomas secreting either lambda 1, lambda 2, lambda 3 or lambda x (recently described) were analysed for V lambda J lambda rearrangements. The results show that in 97% of cases, a single rearrangement occurred, favouring the stochastic model over the ordered one. Strikingly, the possibility of having a productive rearrangement if the first try results in an aberrant one is rare. We propose therefore, that the lambda Ig is not necessarily required to ensure allelic and subtypic exclusion mechanisms. Moreover, in 97% of the cases, at least one kappa allele is rearranged. Furthermore, the RS recombination has been detected in 77% of the cases. This suggests that, although the stimulation of kappa precedes that of lambda locus, the RS recombination acts as a transacting albeit dispensable lambda activator. PMID- 2105885 TI - Hyperpnoea and CO2 sensitivity of the respiratory centres during exercise. AB - The aim of this study was to specify whether exercise hyperpnoea was related to the CO2 sensitivity of the respiratory centres measured during steady-state exercise of mild intensity. Thus, ventilation (VE), breathing pattern [tidal volume (VT), respiratory frequency (f), inspiratory time (TI), total time of the respiratory cycle (TTOT), VT/TI, TI/TTOT] and CO2 sensitivity of the respiratory centres determined by the rebreathing method were measured at rest (SCO2re) and during steady-state exercise (SCO2ex) of mild intensity [CO2 output (VCO2) = 20 ml.kg-1.min-1] in 11 sedentary male subjects (aged 20-34 years). The results showed that SCO2re and SCO2ex were not significantly different. During exercise, there was no correlation between VE and SCO2ex and, for the same VCO2, all subjects had very close VE values normalized for body mass (bm), regardless of their SCO2ex (VEbm0.75 = 1.44 l.min-1.kg-1 SD 0.10). A highly significant positive correlation between SCO2ex and VT (normalised for bm) (r = 0.80, P less than 0.01), TI (r = 0.77, P less than 0.01) and TTOT (r = 0.77, P less than 0.01) existed, as well as a highly significant negative correlation between SCO2ex and (normalised for bm-0.25) (r = -0.73, P less than 0.01). We conclude that the hyperpnoea during steady-state exercise of mild intensity is not related to the SCO2ex. The relationship between breathing pattern and SCO2ex suggests that the breathing pattern could influence the determination of the SCO2ex. This finding needs further investigation. PMID- 2105886 TI - Calcium-ionophore-induced formation of platelet-activating factor and leukotrienes by horse eosinophils: a comparative study. AB - Horse eosinophils preincubated with 3H-labelled acetate and stimulated with the Ca2+ ionophores ionomycin or A23187 form a radioactive compound, which we have shown to be 1-O-alkyl-2-[3H]acetyl-sn-glycero-3-phosphocholine (platelet activating factor). We could detect no 1-O-acyl-2-[3H]acetyl-glycero-3 phosphocholine in the radioactive fraction. The formation of platelet-activating factor was strongly correlated to the generation of leukotriene C4, the main arachidonate metabolite in horse eosinophils, suggesting that platelet-activating factor and leukotriene C4 have a common precursor pool (1-O-alkyl-2-arachidonyl glycero-3-phosphocholine) and a common regulation of synthesis. Even though both ionomycin and A23187 are described as Ca2+ ionophores, they have a series of significantly different effects on the eosinophils with respect to formation of platelet-activating factor and leukotriene C4. While A23187 induces an asymptotic maximum of mediator formation at concentrations higher than 20 microM, ionomycin expressed a narrow optimum at 2 microM. The effects of exogenous pH on the release of mediators also differ strongly between the two ionophores: for A23187 the effects are the same for both mediators but when ionomycin is used as stimulant, generation of platelet-activating factor and leukotriene C4 are affected differently. PMID- 2105887 TI - A factor known to bind to endogenous Ig heavy chain enhancer only in lymphocytes is a ubiquitously active transcription factor. AB - The transcriptional enhancer located in the first intron of the immunoglobulin heavy chain constant region is a major determinant of B-cell-specific expression of immunoglobulin genes. Like other enhancers, the Ig heavy chain enhancer contains several short sequence motifs that bind specific transcription factors. Each binding site contributes to the overall activity of the enhancer, however no single element seems absolutely required for activity. For a better understanding of the Ig heavy chain enhancer components, we have cloned and analyzed individual sequence elements. We find that the factor that binds to the E3 enhancer motif, CATGTGGC, is a ubiquitous transcription factor. It is present in an active form in both B cells and non-B cells, where it can mediate transcriptional activation in vitro and in vivo. However, despite its ability to activate transcription of a transfected reporter gene, the factor is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-lymphoid cells: In previous experiments by others, the characteristic in vivo footprint of this factor, designated NF muE3, was detected in B cells but not in non-B cells. From this and other findings the picture emerges that there are at least three categories of factors which mediate cell-type-specific transcription in B lymphocytes: (a) cell specific factors such as Oct-2A and Oct-2B that are not expressed in most other cell types: (b) ubiquitous factors such as NF-kappa B that are constitutively active in B cells but are sequestered in an inactive form in other cells; (c) ubiquitously active factors, exemplified by the one binding to the E3 sequence motif. This factor is present in an active form in a variety of cell types but is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-B cells, perhaps due to a non-permissive chromatin structure of the Ig heavy chain locus. PMID- 2105888 TI - Purification and properties of an endo-1,4-xylanase excreted by a hydrolytic thermophilic anaerobe, Clostridium thermolacticum. A proposal for its action mechanism on larchwood 4-O-methylglucuronoxylan. AB - An extracellular xylanase from a thermophilic anaerobe, Clostridium thermolacticum, was purified 400-fold by ion-exchange chromatography and gel filtration. The purified enzyme had a specific activity of 31,670 nkat/mg of protein at 60 degrees C, a molecular mass of 39 kDa and a pI of 4.9. The enzyme exhibited maximal activity at 80 degrees C (1 h assay) and at pH 6.0-6.5. There was little loss of activity after 4 days at 60 degrees C and the enzyme was stable in the wide pH range 3-11. Examination of the hydrolysis products of larchwood xylan indicated that it was an endoxylanase; at the early stage of the reaction, xylose (Xyl)-containing oligosaccharides of 3-12 residues were released and after a prolonged incubation time, the neutral end-products were Xyl2 and Xyl3. Kinetic studies of the hydrolysis of xylose-containing oligosaccharides of 4-7 residues showed that the tetrasaccharide was hydrolysed more slowly than the pentasaccharide, while the calculated Km and V values for pentasaccharide and hexasaccharide were similar. The primary structures of the XylnGlcA produced by long-term hydrolysis of larchwood glucuronoxylan were determined on the basis of their carbohydrate composition, by methylation analysis and by 1H-NMR and 13C-NMR spectroscopies. These data allowed us to propose a model for the mode of action of this endoxylanase on larchwood 4-O-methylglucuronoxylan. PMID- 2105889 TI - Pertussis toxin and H-7 distinguish mechanisms involved in eicosanoid release from lipopolysaccharide-primed macrophages. Eicosanoid release from lipopolysaccharide-primed macrophages. AB - Release of eicosanoids is an important response of macrophages to inflammation and bacterial infection. At low concentrations, bacterial lipopolysaccharide (1-2 micrograms/ml) fails to stimulate eicosanoid release in resident peritoneal macrophages but primes the macrophages for a greatly enhanced release of eicosanoids on stimulation with the calcium ionophore A23187 (0.1 microM) or with phorbol 12-myristate 13-acetate (50 nM), an activator of protein kinase C. Incubation of macrophages with Bordetella pertussis toxin, prior to priming with lipopolysaccharide, inhibited the release of both cyclooxygenase and lipoxygenase products upon A23187 stimulation. Pertussis toxin treatment of macrophages had no effect on eicosanoid release when the stimulus was phorbol 12-myristate 13 acetate. The presence of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an effective inhibitor of protein kinase C, during lipopolysaccharide priming and subsequent stimulation significantly inhibited eicosanoid release when phorbol 12 myristate 13-acetate was the stimulus, but did not affect eicosanoid release stimulated by A23187. Based on these results, at least two mechanisms, distinguished by apparent differences in sensitivity to pertussis-toxin sensitive, guanine-nucleotide-binding proteins and protein kinase C, are involved in eicosanoid secretion by lipopolysaccharide-activated macrophages in response to A23187 and phorbol 12-myristate 13-acetate. PMID- 2105890 TI - Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation. AB - The effect of suppression with antimicrobial agents of the intestinal microflora of paediatric bone marrow graft recipients on severe bacterial and fungal infections and on moderate to severe acute graft-versus-host disease was studied retrospectively. Data on 65 cases of bone marrow transplantation for either severe bone marrow failure or leukaemia, performed in a strict protective environment with either complete or selective gastrointestinal decontamination, were evaluated. All bone marrow grafts were from HLA-identical siblings and were not depleted of T-lymphocytes. Twenty percent of the recipients had one or more episodes of septicaemia during the granulocytopenic period after transplantation, mostly due to gram-positive bacteria. Only five children died due to infection, in each case caused by a microorganism originating from the endogenous flora. Complete gastrointestinal decontamination was superior to selective gastrointestinal decontamination in preventing infectious complications (p less than 0.001). The same was the case for the prevention of acute graft-versus-host disease of grade II or higher, which was observed in 7 of 40 (17.5%) completely decontaminated children versus 9 of 18 (50%) selectively decontaminated children evaluable for graft-versus-host disease (p less than 0.01). It is concluded that complete gastrointestinal decontamination in a strict protective environment is a feasible and very effective method for preventing severe infections and acute graft-versus-host disease after allogeneic bone marrow transplantation in children and adolescents; it resulted in a low transplantation-related mortality of 26% and a good quality of survival in 69% of the graft recipients. PMID- 2105891 TI - Survival of gonococci from urethral discharge on fomites. PMID- 2105892 TI - Outbreak of schistosomiasis in a tourist group returning from Mali. PMID- 2105893 TI - Proximal phocomelia and radial ray aplasia in fetal valproic syndrome. AB - We describe a child with multiple congenital anomalies born to a women treated with valproic acid (1000 mg/day) for post traumatic epilepsy. Defects included the typical dysmorphism of the "fetal valproic syndrome", bilateral radial ray aplasia, unilateral proximal phocomelia of the upper limb, kidney hypoplasia and brain atrophy. A direct teratogenic effect of valproic acid is suspected on an experimental basis, and validated by two previous reports of radial defects after valproic acid exposure. PMID- 2105894 TI - [Production of the standard intestinal flora for experimental animals raised under barrier sustained conditions]. PMID- 2105895 TI - Sensitive detection of Mycoplasma pulmonis by using the polymerase chain reaction. AB - Detection of Mycoplasma pulmonis was examined by using the polymerase chain reaction (PCR) for amplifying a specific DNA sequence. In gel electrophoresis which was conducted to detect the amplified products, only 1 pg of M. pulmonis DNA could be detected following 30 cycles of amplification, while no amplified product was detected even from 1 microgram of M. arthritidis or M. neurolyticum DNA. Furthermore, 10 colony-forming units of M. pulmonis could be detected by direct amplification from the mycoplasma suspension. These results suggest the usefulness of the PCR as a highly sensitive, specific, and rapid method for direct detection of M. pulmonis. PMID- 2105896 TI - Mechanism of interaction between interferon-gamma and antineoplastic agent on the differentiation of HL-60 promyelocytic cells. AB - Exposure of HL-60 promyelocytic leukemia cells to a combination of interferon gamma (IFN gamma) and 5-fluorouracil (5-FU), at concentrations ineffective by themselves, induced a significant differentiation into monocyte-like cells. This phenomenon was accompanied by a synergistic antiproliferative effect. Further characterization of these two activities of the IFN gamma/5-FU combination on HL 60 cells was carried out. Whereas a brief pretreatment of the cells with IFN gamma followed by 5-FU was sufficient to exert the synergistic antiproliferative action, the effect on differentiation was dependent on a prolonged concomitant exposure to both drugs. In an attempt to gain more insight into the biochemical mechanisms of these phenomena, we have examined the effects of RNA and protein synthesis inhibitors and of cytoskeleton disrupting agents on the actions of IFN gamma. Inhibition of RNA or protein synthesis by actinomycin D or cycloheximide did not prevent the antiproliferative action of IFN gamma nor the induction of monocytic differentiation, yet these two compounds blocked the priming effect of IFN gamma on the potentiation of 5-FU action. Actinomycin D synergistically potentiated the antiproliferative action of IFN gamma. Colchicine, vinblastine, and cytochalasin B, disrupting the microtubular and microfilament structure, did not interfere with the actions of IFN gamma; higher concentrations of the drugs even improved the priming effect. Exogenous thymidine, known to counteract the antiproliferative effect of 5-FU, also blocked the antigrowth action but not the differentiation induced by the IFN gamma/5-FU combination. The results suggest the existence of two different mechanisms of the IFN gamma/5-FU synergism: one governing the antiproliferative action via an effect on thymidine synthetase, inducible by a short-term IFN gamma pretreatment and dependent on de novo RNA and protein synthesis; and the other mediating the induction of differentiation requiring a long-term exposure of the cells to both drugs. From a clinical point of view, drug combinations such as IFN gamma and 5-FU, inducing differentiation as well as inhibiting proliferation, may suggest a new approach to the treatment of leukemia. PMID- 2105897 TI - Importance of catecholamine release for the functional action of intrastriatal implants of adrenal medullary cells: pharmacological analysis and in vivo electrochemistry. AB - The aim of the present experiments was to test whether adrenal chromaffin cells implanted into the striatum of rats could exert a functional effect through a release of catecholamines. A cell suspension obtained from bovine adrenal medulla was implanted unilaterally into the striatum. The striatal dopaminergic input was extensively destroyed beforehand to preclude the possibility of reinnervation of the striatum by endogenous dopaminergic neurons. The functional influence of the implant was tested through the measurement of drug-induced rotation, while catecholamine release was measured subsequently in the same animals by in vivo electrochemistry. Transplant survival, as shown by the immunohistochemical analysis performed at the end of the in vivo experiments, was highly variable. Surviving chromaffin cells maintained their endocrine morphology and no reinnervation of the host striatum could be detected. Rotation of the animals evoked by apomorphine (0.1 mg/kg, sc) or amphetamine (5.0 mg/kg, ip) following the lesion was left uninfluenced following transplantation, even when a large transplant was recovered. On the other hand, nicotine (0.5 mg/kg, sc) evoked a strong contraversive rotational response in the transplant-bearing animals. This response could not be ascribed to the central effect of substances released peripherally and entering the nervous system through the blood-brain barrier opened by the implantation procedure, as it could not be found in animals bearing implants of other peripheral endocrine tissue, viz, pituitary. The effect of nicotine was not blocked by the pretreatment of the animals with either the opiate antagonist naloxone (2.5 mg/kg, 10 min) or the dopamine receptor blocker pimozide (0.5 mg/kg, 1 h), although the latter pretreatment blocked the amphetamine-evoked rotation. No spontaneous catecholamine release could be detected from the implanted chromaffin cells by in vivo electrochemistry, while treatment with amphetamine or nicotine did evoke a release. The results suggest that the functional effects of such intrastriatal grafts of chromaffin cells, reported in previous studies, cannot be explained by the secretion from the grafted cells of catecholamines into the denervated striatum. On the other hand the results obtained following the pharmacological stimulation of these cells indicate that adrenal grafts can, under suitable conditions, influence the functioning of the host nervous system. PMID- 2105898 TI - Dopamine and octopamine in whole body extracts of the bulb mite. AB - Using high performance liquid chromatography with electrochemical detection, whole body extracts of the bulb mite, Rhizoglyphus echinopus (Fumouze and Robin), were found to contain the biogenic amines dopamine and octopamine at concentrations of 4.3 +/- 0.6 and 2.3 +/- 1.4 ng g-1 wet weight, respectively. Adrenaline, noradrenaline, tyramine, N-methyldopamine, N-acetyldopamine, and 5 hydroxytryptamine, if present, were below the limits of detectability. This is the initial demonstration of the presence of octopamine in a mite species. PMID- 2105899 TI - Treatment failure in trichomoniasis and persistence of the parasite after Lactobacillus immunotherapy; two case reports. AB - This report describes the clinical and laboratory observations on two patients with a Trichomonas vaginalis infection resistant to metronidazole. The metronidazole resistance was confirmed in in vitro cultures under aerobic conditions, after in vitro cultivation of the strains. Trichomonas infection persisted during high-dose intravenous metronidazole administration and Lactobacillus immunotherapy was unsuccessful in both patients. PMID- 2105900 TI - Plasminogen activator inhibitors: hormonally regulated serpins. PMID- 2105902 TI - Geriatric assessment: costs and benefits. PMID- 2105901 TI - Talin and vinculin in the oocytes, eggs, and early embryos of Xenopus laevis: a developmentally regulated change in distribution. AB - We have investigated the expression and distribution of talin and vinculin in the oocytes, eggs, and embryos of Xenopus laevis. Antibodies to the previously characterized avian proteins stain several different Xenopus cell types identically by immunofluorescence: adhesion plaques of cultured kidney (A6) cells, the cell peripheries of oviduct cells, and the postsynaptic neuromuscular junctions of tadpole tail muscle fibers. These antibodies also identify cognate proteins of the appropriate sizes on immunoblots of A6 cell and oviduct lysates. Using these antibodies on ovarian tissue, we find talin to be highly localized at the cortices of oocytes and vinculin to be in the oocyte cytoplasm and absent from the oocyte cortex. In the cells of the ovarian layers that surround the oocytes, talin and vinculin can be detected as soluble and cytoskeletal components. Vinculin is first detectable as a cytoskeletal component in eggs, appearing some time during or between oocyte maturation and oviposition. During early embryo development, talin and vinculin are colocalized in the cortex of cleavage furrows and blastomeres. Thus, Xenopus oocytes and eggs display different distributions of talin and vinculin. The change from unlinked localization to colocalization appears to be developmentally regulated, occurring during the transition from oocyte to egg. PMID- 2105903 TI - [Progress in the study of muscarinic acetylcholine receptors; establishment of the subtypes or subgroups]. AB - Since acetylcholine (ACh) was identified as a neurotransmitter at parasympathetic nerve terminals by pioneering pharmacologists such as O. Schmiedeberg, R. Hunt, O. Loewi and H.H. Dale, muscarinic acetylcholine receptors (mACh-R) serving as a transducer of muscarinic action have been assumed to exist. After many tries to identify the mACh-R, it's existence was established by the group of S.H. Snyder, who employed binding assays with the radioligand 3H-QNB. The presence of a neuronal (M1) and a peripheral (M2) mACh-R was suggested from the action of an M1 specific agonist, McN-A-343; and this observation was followed by the discovery that the antagonist pirenzepine had higher affinity for M1 than for M2. Later, peripheral mACh-Rs were further subclassified in two types by the heart-specific action of gallamine and the different affinities of AF-DX116 and 4-DAMP. At present, three subtypes, M1 (neuronal), M2 (heart) and M3 (other peripheral organs), can be pharmacologically distinguished by affinity differences. On the other hand, purification of mACh-R and analysis by gene technology revealed the presence of five mACh-R mRNAs (m1-m5), which were expressed in various organs with different abundances. These subtypes couple with subcellular muscarinic responses through different GTP-binding proteins. The connection between the subtypes, GTP-binding proteins and responses is not fully understood yet. Our studies showed that in guinea pig heart, in which only m2 mRNA is expressed, muscarinic agonists recognize two subgroups (M2 alpha and M2 beta) with different affinities. One couples with the inhibition of adenylate cyclase, and the other couples with PI turnover through different GTP-binding proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105905 TI - ROI principles replace guesswork in purchasing. PMID- 2105904 TI - Predicting length of hospital stay for psychiatric inpatients. AB - Medicare's use of diagnosis-related groups and the frequent acceptance of length of stay as an indicator of resource utilization has caused a surge of interest in the predictability of length of hospital stay for psychiatric inpatients. By constructing a weighted least squares regression model using data from the 1980 Hospital Discharge Survey, the authors were able to account for an increased amount of variance in length of stay for the major diagnostic categories of mental disorder and substance abuse for Medicare and Blue Cross/Blue Shield patients. The enhanced ability to predict length of stay is attributed to a carefully constructed data base and an increased number of predictor variables, particularly comorbidity. Knowledge of the presence or absence of a chemical dependency unit in the hospitals from which patients were discharged substantially increased the proportion of variance accounted for in the analysis. PMID- 2105906 TI - Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA. AB - In order to search for mutations resulting in hemophilia A that are not detectable by restriction analysis, three regions of the factor VIII gene were chosen for direct sequence analysis. Short segments of genomic DNA of 127 unrelated patients with hemophilia A were amplified by polymerase chain reaction. A total of 136,017 nucleotides were sequenced, and four mutations leading to the disease were found: a frameshift at codon 360 due to deletion of two nucleotides (GA), a nonsense codon 1705 due to a C----T transition, and two missense codons at positions 1699 and 1708. The first missense mutation (A----T) results in a Tyr ---Phe substitution at a putative von Willebrand factor binding site. The second results in an Arg----Cys substitution at a thrombin cleavage site. In addition, we identified three rare sequence variants: a silent C----T transition at codon 34 which does not result in an amino acid change, a G----C change at codon 345 (Val----Leu), and an A----G change at the third nucleotide of intron 14. Direct sequence analysis of amplified DNA is a powerful but labor-intensive method of identifying mutations in large genes such as the human factor VIII gene. PMID- 2105907 TI - The I-J-disparate mouse strains B10.A(3R) and B10.A(5R) have identical E beta sequences. PMID- 2105908 TI - Slow response variant of the B lymphoma 70Z/3 defective in LPS activation of NF kappa B. AB - The mouse B cell lymphoma 70Z/3 is membrane immunoglobulin M (mIgM) negative, but treatment of the cells with bacterial lipopolysaccharide (LPS) induces the expression of kappa (kappa) light chain synthesis, and the cells become mIgM+. In wild type cells, this reaction is maximal after 24 h; we have isolated a variant, 1B8, which becomes mIgM+ only after a more prolonged incubation with LPS. This delayed response results from a reduced rate of accumulation of (kappa) mRNA and protein. The transcription factor, NF-kappa B is present in the cytoplasm of both the wild type and the variant cells in its inactive form. The delay in kappa expression is correlated with the failure of NF-kappa B to be activated and translocated to the nucleus. Although NF-kappa B cannot be activated by LPS, it can be activated by treatment with phorbol ester (PMA). In contrast to the clear defect in NF-kappa B, LPS treatment of 1B8 cells causes the octamer-binding factor OTF-2 to increase normally. We conclude that the defect in 1B8 cells is in an early part of the LPS activation pathway, prior to the activation of NF-kappa B, but after the signal for OTF-2 induction. The phenotype of 1B8 demonstrates that an increase in OTF-2 alone is sufficient to cause a large increase in kappa transcription in 70Z/3 cells, but that without NF-kappa B, the response is slow to develop. In this view, NF-kappa B functions to facilitate kappa transcription and to speed its rate of increase, but is not required for the long-term response of 70Z/3 cells to LPS. PMID- 2105909 TI - Adrenergic receptors. Models for regulation of signal transduction processes. AB - Adrenergic receptors are prototypic models for the study of the relations between structure and function of G protein-coupled receptors. Each receptor is encoded by a distinct gene. These receptors are integral membrane proteins with several striking structural features. They consist of a single subunit containing seven stretches of 20-28 hydrophobic amino acids that represent potential membrane spanning alpha-helixes. Many of these receptors share considerable amino acid sequence homology, particularly in the transmembrane domains. All of these macromolecules share other similarities that include one or more potential sites of extracellular N-linked glycosylation near the amino terminus and several potential sites of regulatory phosphorylation that are located intracellularly. By using a variety of techniques, it has been demonstrated that various regions of the receptor molecules are critical for different receptor functions. The seven transmembrane regions of the receptors appear to form a ligand-binding pocket. Cysteine residues in the extracellular domains may stabilize the ligand binding pocket by participating in disulfide bonds. The cytoplasmic domains contain regions capable of interacting with G proteins and various kinases and are therefore important in such processes as signal transduction, receptor-G protein coupling, receptor sequestration, and down-regulation. Finally, regions of these macromolecules may undergo posttranslational modifications important in the regulation of receptor function. Our understanding of these complex relations is constantly evolving and much work remains to be done. Greater understanding of the basic mechanisms involved in G protein-coupled, receptor-mediated signal transduction may provide leads into the nature of certain pathophysiological states. PMID- 2105910 TI - Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell. AB - Indapamide, a nonthiazide diuretic, exhibits direct vasodilator action as well as natriuretic and diuretic effects. Although calcium antagonist-like activity has been addressed so far, the mechanisms for vasodilator effect are still uncertain. To understand the wide range of indapamide actions, we examined the effects of indapamide on the vascular eicosanoid generation and investigated its mechanisms by using rat vascular smooth muscle cells in culture. Indapamide uniquely increased the prostacyclin generation in the vascular smooth muscle cells in a dose-dependent manner, whereas it did not affect the vasoconstrictor thromboxane A2. Thiazide diuretics lowered the prostacyclin generation, while nonthiazide derivatives did not affect the biosynthesis. Enzymatic analysis revealed that indapamide affected neither [14C]arachidonate liberation nor prostacyclin synthase of the smooth muscle cells. Indapamide eliminated a stable free radical in a cell-free system, lowered the formation of malondialdehyde from lipid peroxides in rat brain homogenate, and reduced lipid peroxidation by the free radical generating system of xanthine-xanthine oxidase. Indeed, the scavenging action of indapamide significantly attenuated the inhibitory activity of 15 hydroperoxy-arachidonate to prostacyclin synthase activity. These results indicate that indapamide diuretic increases prostacyclin generation in the vascular smooth muscle cells possibly through antioxidant effects and that the enhanced prostacyclin generation is partly responsible for its direct vasodilator action. PMID- 2105911 TI - Effect of ornithine decarboxylase inhibitor on tetragastrin treatment of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. AB - The effects of combined administration of tetragastrin and the ornithine decarboxylase inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and the BUdR labelling indices of the fundic and antral mucosae, were investigated in inbred Wistar rats. Rats were given drinking water containing 2.5 g/l of DAP ad libitum and received alternate-day injections of 1 mg/kg body weight of tetragastrin in depot form after 25 weeks of oral treatment with MNNG. At week 52, prolonged administration of tetragastrin alone resulted in a significant reduction in the incidence and number of gastric cancers and a significant increase or decrease in the labelling indices of the fundic and antral mucosae, respectively. Concomitant administration of tetragastrin and DAP had no effect on the inhibition by tetragastrin of gastric carcinogenesis. With this treatment, the labelling index was significantly reduced in the fundic mucosa but not in the antral mucosa. These results suggest that ODC inhibitor does not attenuate tetragastrin inhibition of gastric carcinogenesis, and that anti-trophic action of tetragastrin on antral mucosa may be related to tetragastrin inhibition of gastric carcinogenesis. PMID- 2105912 TI - Relationship between the inhibition of receptor-induced increase in cytosolic free calcium concentration and the vasodilator effects of nitrates in patients with congestive heart failure. AB - Nitroglycerin, isosorbide dinitrate and sodium nitroprusside, like nifedipine, were found to inhibit the receptor-provoked increase of cytosolic free calcium concentration in human platelets loaded with 2-[(2-amino-5-methylphenoxy)methyl] 6-methoxy-8-aminoquinoline-N,N,N',N' - tetraacetate. Sodium nitroprusside and nitroglycerin induced elevation of cyclic guanosine 3',5'-monophosphate content in platelets which correlated with their calcium-blocking activity. Methylene blue and epinephrine decreased the calcium-blocking effect and the influence of nitroglycerin on cyclic guanosine 3'-5'-monophosphate content, but failed to suppress the inhibitory effect of sodium nitroprusside. Ascorbic acid increased the calcium blocking effect of sodium nitroprusside and its influence on cyclic guanosine 3'-5'-monophosphate content, but did not alter the inhibitory effect of nitroglycerin. In order to evaluate the relationship between the mode of action of nitrates at cellular level and their vasodilatory effectiveness, we studied the circulatory response of the forearm to isosorbide dinitrate and the influence of nitroglycerin on free calcium concentration in the platelets in 10 patients with chronic heart failure. We established a significant positive correlation between the basal values for venous tone and its peak decrease after administration of the 10-mg dose of isosorbide dinitrate. A correlation was also found between the deviation of maximal decrease of venous tone by this dose of isosorbide dinitrate from the regression line (the relationship between the basal venous tone and its lowering by the drug) and mean inhibitory concentration values for nitroglycerin in blocking that proportion of the rise of calcium ion concentration in platelets due to blocking of the platelet-activating factor. Thus, nitrates, like calcium antagonists, inhibit the receptor-provoked calcium supply to the contractile system of the cells so neutralizing the effects of increased concentrations of vasoconstrictors. This suggests that the effectiveness of nitrates appears to be positively related to the contribution of receptor-induced increase of cytosolic free calcium concentration in vasoconstriction together with their capacity to raise cyclic guanosine 3',5' monophosphate. PMID- 2105913 TI - Preclinical screening and analysis of the immunotoxic and immunomodulatory activity using a multiple immunoassay (MIA) in mice. AB - Screening and analysis of immunotoxic and immunomodulatory activity has become an integral component in preclinical studies of pharmaceuticals and xenobiotics. In an attempt to replace laborious and expensive batteries of assays used at present we developed a multiple immunoassay (MIA) enabling the determination, in a single mouse, of: the weight of the thymus, spleen and a group of lymph nodes; delayed type hypersensitivity and antibody response to SRBC; phagocytic activity of peritoneal macrophages and the responsiveness of spleen lymphocytes to "T" (PHA, ConA) and "B" (LPS) mitogens in vitro. The MIA responsiveness to two prototype immunostimulators (Thymostimulin and Listeria factor Ei) was tested at two time periods after antigenic stimulation, not only in normal mice, but also in animals with selectively depressed T-systems (anti-Thy1.2 monoclonal antibody) and B systems (cyclophosphamide); in both dexamethasone-treated and irradiated animals. The findings indicate, that this MIA is capable of reflecting both immunosuppressive and immunostimulatory activities of the tested agents and permits partial insight into the mechanisms underlying these activities. PMID- 2105914 TI - Protein kinase C inhibitors enhance concanavalin A cap formation in polymorphonuclear leukocytes. AB - The potent protein kinase C (PKC) inhibitors, 1-(5-isoquinolinesulfonyl)-2 methylpiperazine dihydrochloride (H-7) and staurosporine, significantly enhanced concanavalin A (Con A)-induced cap formation in polymorphonuclear leukocytes (PMNs) from C57BL/6 mice after pretreatment for 30 min at concentrations of 10 microM and 1 nM, respectively. However, neither 10 microM of N-(2-aminoethyl)-5 isoquinolinesulfonamide dihydrochloride (H-9) nor N-(2-guanidinoethyl)-5 isoquinolinesulfonamide hydrochloride (HA1004), which inhibit cyclic nucleotide dependent protein kinases more effectively than other kinases, affected the capping. Meanwhile, treatment of PMNs with Con A induced the translocation of PKC from the cytosol to the membrane fraction within 5 min, which is considered to be important for the activation of this enzyme. When cells were pretreated with H-7 or staurosporine for 30 min at the concentrations that enhanced the capping, both the cytosolic and the membrane-bound PKC activity was inhibited during the further incubation with Con A. These results suggest that PKC may play an important role in the regulation of Con A-induced cap formation in PMNs. PMID- 2105915 TI - Effect of murine recombinant interferon-gamma in the protection of mice against Salmonella. AB - The ability of recombinant murine (rMu) interferon (IFN)-gamma to activate anti Salmonella-activity in normal mice and beige mutant (bg/bg) mice with Chediak Higashi syndrome (CHS) was examined. Previous intraperitoneal (i.p.) injection of rMuIFN-gamma (10(4) U per mouse) significantly hindered the bacterial growth in the peritoneal cavities, spleens and livers of the mice after the i.p. infection with Salmonella enteritidis No. 11 strain. It was also effective on the beige mice that have phagocytic cells with a genetically impaired bactericidal function, suggesting that IFN-gamma activates the pathway irrelevant to the beige mutation. The effect was the maximum, when IFN-gamma was given 6 h before the challenge. The effect seemed to be due to the augmentation of bactericidal capacity rather than the prevention of systemic spread of bacteria. Recombinant human IFN-alphaA/D (10(2)-10(6) U per mouse), which produced effects identical to those of murine IFN-beta, did not show such a bactericidal effect. Bactericidal activity enhancement was also seen in mice that had been injected with a small amount of rMuIFN-gamma (10(2) U) and bacterial lipopolysaccharide (LPS) (10 ng) together at 6 h before the challenge, although the IFN-gamma or LPS alone at these doses produced very little if any effect. Bactericidal effect enhancement was seen in mice that had been injected with IFN-gamma at 6 h and LPS at 3 h before the challenge, while it could be hardly seen in mice injected with them in a reversed order.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105916 TI - Intraocular in vivo immunofluorescence. A new technique for visualizing structures of the ocular fundus. AB - A new noninvasive technique for observing structures in the living eye has been developed: the technique is based on intravenous application of specific antibodies, labeled with fluorescein. The immunologically marked substructures of the fundus of the eye, the only transparent organ in mammals, are photographed directly using high speed film. Combined with a digital image processor to enhance low contrast contours, this technique can be used for diagnostic purposes, as shown in rabbits with experimental toxoplasmic chorioretinitis. PMID- 2105917 TI - Layer-by-layer desquamation of corneal epithelium and maturation of tear-facing membranes. AB - A method to devitalize single layers of apically exposed rabbit corneal epithelial cells through the use of digitonin is described. Devitalized cells exfoliate spontaneously as loosely cohesive, trypan-blue-stained layers, exposing underlying viable cells. Repeated application of this devitalization-exfoliation methodology results in the gradual elimination of each of the epithelial cells. The generation of corneal surfaces composed of the tear-facing membranes of all intraepithelial cell types--subsurface, wing, and basal--is thus attainable. Exposed surfaces were studied with respect to microanatomy, the binding of lectins, and the adherence of Pseudomonas aeruginosa. Microprojections (microvilli or microplicae) were absent in the basal cells but were present in all suprabasal layers, and increased gradually in density as cells approached the surface position. Wheat germ agglutinin and concanavalin A were found to bind to the tear-facing membranes of all suprabasal cell layers. The tear-facing membrane of the basal cells, in contrast, was not labeled. Within each labeled layer, the magnitude of lectin binding differed markedly from cell to cell; lectin binding decreased as the cellular area exposed to the tear surface increased. Pseudomonas were found exclusively at microprojection-free cellular areas, suggesting that inhibition of attachment is linked to the ontogeny of these microprojections. PMID- 2105918 TI - Forecasts from Iowa health care experts. PMID- 2105919 TI - The case for hospital diversification into long-term care. AB - Since the market for long-term care (LTC) services is expected to grow rapidly in the years ahead, the case for hospital diversification into LTC is a strong one. This article discusses the major LTC diversification options, the cost of entry, potential profitability, potential problems, and recommendations for implementing them. PMID- 2105920 TI - Thoracic irradiation in Hodgkin's disease: disease control and long-term complications. AB - A total of 590 patients with Stage IA-IIIB Hodgkin's disease received mantle irradiation at the Joint Center for Radiation Therapy between April 1969 and December 1984 as part of their initial treatment. Recurrence patterns as well as pulmonary, cardiac and thyroid complications were analyzed. Pulmonary recurrence was more frequently seen in patients with large mediastinal adenopathy (LMA); 11% of patients with LMA recurred in the lung in contrast to 3.1% with small or no mediastinal disease, p = 0.003. Hilar involvement, when corrected for size of mediastinal involvement, was not predictive of lung relapse. Patients with LMA also had a high rate of nodal relapse above the diaphragm (40%) following radiation therapy (RT) alone as compared to similarly treated patients with small or no mediastinal adenopathy (6.5%), p less than 0.0001. This risk of nodal recurrence was greatly reduced (4.7%) for LMA patients receiving combined radiation therapy and chemotherapy (CMT), p less than 0.0001. Sixty-seven patients (11%) with hilar or large mediastinal involvement received prophylactic, low dose, whole lung irradiation. No decrease in the frequency of lung recurrence was seen with the use of whole lung irradiation. Radiation pneumonitis was seen in 3% of patients receiving radiation therapy alone. In contrast, the use of whole lung irradiation was associated with a 15% risk of pneumonitis, p = 0.006. The risk of pneumonitis was also significantly increased with the use of chemotherapy (11%), p = 0.0001. Cardiac complications were uncommon with pericarditis being the most common complication (2.2%). Thyroid dysfunction was seen in 25% of patients and appeared to be age-related. These data suggest that the long-term complications of mantle irradiation are uncommon with the use of modern radiotherapeutic techniques. The use of prophylactic whole lung irradiation is no longer recommended since its use did not reduce pulmonary relapse but did increase the risk of pneumonitis. Chemotherapy is also associated with an increased risk of pneumonitis, however, its use in patients with large mediastinal adenopathy appears justified. PMID- 2105921 TI - Bowel complications after radiotherapy for carcinoma of the prostate: the volume effect. AB - Late radiation-induced bowel complications were studied in 218 patients treated for localized carcinoma of the prostate by radical radiotherapy at the Prince of Wales Hospital between 1980 and 1986. Mild to moderate toxicity was seen in 38 cases, and severe toxicity requiring surgery occurred in 3 patients. The total actuarial complication rate (by 5 years) for all grades was 24% and for severe complications was 1.8%. Significant patient-related risk factors were older age at the time of radiotherapy (p = 0.035) and a previous history of abdominal operations (p = 0.028). Among treatment-related risk factors only inclusion of the whole pelvis in the irradiated volume had a significant association with this complication (p = 0.015). The risk of bowel complications was not related to the total radiation dose or to the use of interstitial implants as employed in this series. PMID- 2105922 TI - Trimodality therapy (drug/hyperthermia/radiation) with BCNU or mitomycin C. AB - To develop multimodality treatment combinations with high curative potential in advanced local disease, BCNU (N,N'-bis(2-chloroethyl)-N-nitro-sourea) and mitomycin C were tested with hyperthermia and radiation in the FSaIIC fibrosarcoma system. Growth delay experiments demonstrated that, while neither BCNU nor mitomycin C produced dose modification of the radiation response, and hyperthermia (43 degrees C, 30 min) produced only a moderate dose modification (1.4 +/- 0.2), the combination of BCNU plus hyperthermia resulted in a radiation dose modifying factor (DMF) of 1.9 +/- 0.3, and mitomycin C plus hyperthermia a dose modifying factor of 2.1 +/- 0.4. Tumor cell survival over a range of BCNU doses administered i.p. immediately before hyperthermia resulted in a dose modifying factor of 1.8 +/- 0.2 versus drug alone. With mitomycin C however, giving the drug immediately prior to heating produced a dose modifying factor due to hyperthermia of only 1.2 +/- 0.10. Hoechst 33342 diffusion was used to separate tumor cells into predominately oxic and hypoxic subpopulations. Administration of the single, double and trimodality therapies showed that BCNU was 3.1-fold more toxic to the oxic versus the hypoxic cells whereas mitomycin C was 3.5-fold more toxic to the hypoxic compared to the oxic cells. Hyperthermia was 1.4-fold more toxic to the hypoxic versus the oxic cells whereas 10 Gy of radiation was 2.0-fold more toxic to the oxic compared to the hypoxic cells. The combination of hyperthermia plus radiation increased killing in both Hoechst dye defined subpopulations but relatively more in the hypoxic cells in which killing was 1.8-fold greater than in the oxic cells. When heat was delivered immediately after i.p. administration of the anticancer drugs, hyperthermia increased BCNU killing in the oxic cells by 17.2-fold versus 4.4-fold in the hypoxic cells and increased mitomycin-killing by 2.6-fold in the oxic cells versus 17-fold in the hypoxic cells. Use of the full trimodality treatment, given in the sequence drug (BCNU, 50 mg/kg or mitomycin-C 5 mg/kg)----heat (43 degrees C, 30 min)--- radiation (10 Gy) produced a 3 log kill in the oxic cells versus a 2 log kill in the hypoxic cells with BCNU and a 2 log kill in the oxic cells versus a 3 log kill in the hypoxic cells with mitomycin C. These results indicate that the use of selected anticancer drugs with hyperthermia and radiation can produce highly cytotoxic interactions which markedly modify the effect of radiation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2105923 TI - Radiation qualities of x-ray beams in cooperative clinical trials. AB - X-ray beams are usually described by "MV" numbers which represent accelerating potentials (AP) and approximations to the maximum energies in the photon spectra. However, these numbers do not uniquely specify the properties of the beams. Current high energy photon dosimetry protocols specify radiation quality in terms of a measured ionization ratio which is equivalent to the ratio of the tissue maximum ratios at depths 10 cm and 20 cm, for field size 10 cm X 10 cm [TMR)20(10]. For convenience, the American Association of Physicists in Medicine introduced a new parameter, known as the Nominal Accelerating Potential (NAP), which was derived from (TMR)20(10) and features values in MV units that are similar to those of the conventional accelerating potentials. (TMR)20(10) and Nominal Accelerating Potential may be considered to be expressions of the penetrating powers of x-ray beams. We determined (TMR)20(10) and Nominal Accelerating Potential for 460 treatment machines with stated accelerating potentials from 4 MV to 25 MV in the Quality Assurance Review Center's files of machine data from institutions that participate in cooperative clinical trials. The results demonstrate appreciable variability of the two parameters at each stated accelerating potential, with overlapping of adjacent groups of machines. It is concluded that the manufacturers' MV numbers do not reliably identify x-ray beams in terms of their depth dose properties. To promote standardization and consistency of energy specification in clinical trials as well as in general practice, we propose that x-ray beams be designated by their Nominal Accelerating Potential values as an adjunct to the use of (TMR)20(10) in radiation therapy. PMID- 2105924 TI - Influence of hip prostheses on high energy photon dose distributions. AB - Radiotherapy treatment of patients having a hip prosthesis is a common problem facing dosimetrists and physicists when the treatment plan requires irradiation of the pelvic area. To quantify the perturbation of these devices, attenuation studies were done with 6 and 18 MV photon beams using various hip prostheses models with varying size and composition. These studies have shown that an attenuation of as much as 50% can be found in a single beam profile under the prosthesis. We have studied the capability of a dose planning system to predict the transmission of these devices as compared with measurements. PMID- 2105925 TI - High serum trypsin-like immunoreactivity secondary to pancreatitis in a dog with exocrine pancreatic insufficiency. AB - A 13-year-old spayed Doberman Pinscher with acute vomiting of 24 hours' duration and concurrent 2-week history of polyphagia with weight loss had diabetic ketoacidosis complicated by acute pancreatitis and exocrine pancreatic insufficiency. Diagnostic testing for exocrine pancreatic insufficiency, by determining serum trypsin-like immunoreactivity, revealed an unexpectedly high result when a low result was anticipated. High trypsin-like immunoreactivity was attributed to acute pancreatic inflammation. PMID- 2105926 TI - Portal-drained visceral flux of nutrients in lambs fed alfalfa or maintained by total intragastric infusion. AB - An experiment was performed using lambs fitted with chronic indwelling catheters in appropriate blood vessels for portal-drained visceral (PDV) flux measurements. The objective of the experiment was to evaluate PDV nutrient flux in alfalfa-fed and intragastrically infused lambs and to evaluate the effects of amount of energy and N infused on PDV nutrient metabolism. Lambs were fed alfalfa or infused with 1.64 and 10.9; 1.82 and 12.3; or 2.37 and 15.0 Mcal GE and g N/d, respectively. Arterial concentrations and PDV fluxes of glucose, L-lactate, acetate and portal blood flow were not different (P greater than .10) between alfalfa-fed and infused lambs. Net flux of alpha-amino N, ammonia N and branched chain VFA were lower (P less than .05) and net flux of propionate, butyrate and total VFA were higher for intragastric infusion vs alfalfa. No consistent differences in PDV fluxes were noted among the three levels of energy and N infused, although the energy and N levels tested were near maintenance requirements. Nitrogen retention increased as level of energy and N infusion increased. Approximately 47, 70 and 22% of ruminally infused acetate, propionate and butyrate, respectively, were found on a net basis in portal blood as VFA. Measurements of net nutrient utilization by the PDV that eliminate the influence of ruminal fermentation are possible. How the changes in PDV tissues due to intragastric infusion influence these estimates is unknown. PMID- 2105927 TI - Nitrogen metabolism and somatotropin secretion in lambs receiving arginine and ornithine via abomasal infusion. AB - Sixteen wether lambs (25 kg) were fitted with abomasal infusion cannulas and used to study N and endocrine responses to abomasal infusions of arginine (ARG) or ornithine (ORN). Lambs were randomly allotted to four treatment groups and abomasally infused with solutions of water (CON), ARG, ORN or UREA. The ARG solution provided .50 g ARG.HCl/kg BW and was equimolar with ORN.HCl (.40 g/kg). UREA (.28 g/kg) was isonitrogenous with ARG and served as a positive N control. Lambs were housed in metabolism crates for excreta collection and received 729 g DM/d of a 13.7% CP diet in equal portions four times daily. Following a 7-d dietary adjustment period, lambs were infused continuously (2 liters/d) with water for a 5-d preliminary collection period (Period 1), which immediately preceded a 7-d infusion and collection period (Period 2). Sequential blood samples were taken at 15-min intervals for 8 h between 1200 and 2000 on d 4 of both periods. Single samples were obtained at 1500 on remaining days. Nonrepeated measurements were analyzed as a completely randomized design, whereas repeated measurements were analyzed as a split-plot over time. Period 2 measurements were adjusted using covariance techniques if differences among treatment groups were observed for Period 1. Contrasts used in determining treatment effects were: CON vs UREA, CON vs ARG + ORN, and ARG vs ORN. Nitrogen retention was similar for all treatment, suggesting that dietary N was not limiting. Arginine and ORN increased serum ornithine (P less than .05), blood urea N (BUN; P less than .10) and urinary urea N excretion (P less than .01), whereas ARG increased (P less than .05) serum arginine and UREA increased (P less than .01) BUN and urinary urea N. Serum insulin and glucose were not affected by treatment. Compared with CON, ARG and ORN increased (P less than .05) mean somatotropin (STH) concentration (13.8 vs 16.9 and 18.4 ng/ml) and amplitude of STH pulses (9.8 vs 15.1 and 17.8 ng/ml), whereas CON and UREA were similar. Abomasal infusions of ARG and ORN were equally efficacious in stimulating ovine STH secretion when dietary N intake was not limiting. PMID- 2105928 TI - Effect of long-term administration of porcine growth hormone-releasing factor and(or) thyrotropin-releasing factor on growth hormone, prolactin and thyroxine concentrations in growing pigs. AB - Long-term administration of porcine growth hormone-releasing factor (pGRF(1 29)NH2) and(or) thyrotropin-releasing factor (TRF) was evaluated on serum concentrations of growth hormone (GH) thyroxine (T4) and prolactin (PRL). Twenty four 12-wk-old female Yorkshire-Landrace pigs were injected at 1000 and 1600 for 12 wk with either saline, pGRF (15 micrograms/kg), TRF (6 micrograms/kg) or pGRF + TRF using a 2 x 2 factorial design. Blood samples were collected on d 1, 29, 57 and 85 of treatment from 0400 to 2200. Areas under the GH, T4 and PRL curves (AUC) for the 6 h (0400 to 1000) prior to injection were subtracted from the postinjection periods (1000 to 1600, 1600 to 2200) to calculate the net hormonal response. The AUC of GH for the first 6 h decreased similarly (P less than .05) with age for all treatments. The GH response to GRF remained unchanged (P greater than .10) across age. TRF alone did not stimulate (P less than .05) GH release but acted in synergy with GRF to increase (P less than .05) GH release. TRF stimulated (P less than .001) the net response of T4 on all sampling days. Animals treated with the combination of GRF + TRF showed a decreased T4 AUC during the first 6 h on the last three sampling days. Basal PRL decreased (P less than .05) with age. Over the four sampling days, animals injected with TRF alone showed (P less than .01) a reduction (linear effect; P less than .01) followed by an increase (quadratic effect; P less than .05) in total PRL concentration after injection; however, when GRF was combined with TRF, such effects were not observed (P greater than .10). Results showed that 1) chronic injections of GRF for 12 wk sustained GH concentration, 2) TRF and GRF acted synergistically to elevate GH AUC, 3) TRF increased T4 concentrations throughout the 12-wk treatment period, 4) chronic TRF treatment decreased the basal PRL concentration and 5) chronic GRF + TRF treatment decreased the basal concentration of T4. PMID- 2105929 TI - Cloning and expression of the gene encoding Lactobacillus casei folylpoly-gamma glutamate synthetase in Escherichia coli and determination of its primary structure. AB - A genomic library of Lactobacillus casei DNA containing 10,000 individual clones was constructed in the plasmid pUC13. The gene encoding the L. casei folylpolyglutamate synthetase was isolated from the library by complementation of a folC mutant of Escherichia coli. The gene was expressed in E. coli from its own promoter and produced amplified folylpolyglutamate synthetase activity with properties identical with those of the purified L. casei enzyme. The absence of dihydrofolate synthetase activity and the preferential utilization of 5,10 methylenetetrahydrofolate, rather than 10-formyltetrahydrofolate as folate substrate, distinguishes this activity from the E. coli folylpolyglutamate synthetase-dihydrofolate synthetase. A protein of Mr = 43,000, identical with that of purified L. casei folylpolyglutamate synthetase, was expressed in maxicells containing the complementing plasmid. The nucleotide sequence of the folylpolyglutamate synthetase gene was determined. An open reading frame of 1,284 bases was found predicting a protein product of 428 amino acids with Mr = 44,169. The predicted amino acid sequence of the gene is 33% homologous to that of the E. coli folylpolyglutamate synthetase. Primer extension studies indicate that the transcription initiation site is at -59 base pairs, relative to the initiation ATG codon of the folylpolyglutamate synthetase gene, suggesting that the gene is transcribed independently of upstream genes. A second open reading frame was found downstream of the folylpolyglutamate synthetase open reading frame, overlapping the final codon by 1 base pair. This downstream gene may be co transcribed with the folylpolyglutamate synthetase gene. PMID- 2105930 TI - Binding of tissue-type plasminogen activator with human endothelial cell monolayers. Characterization of the high affinity interaction with plasminogen activator inhibitor-1. AB - The formation and release of covalent complexes between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) limits the application of equilibrium radioligand binding analysis to characterize the interaction between t-PA and human umbilical vein endothelial cell (HUVEC) monolayers. To avoid this difficulty, we used a recombinant mutant of t-PA, S478A rt-PA, in which alanine has been substituted for the active-site serine. Although the mutant is incapable of covalently reacting with PAI-1, 125I-labeled S478A rt PA binding to HUVEC monolayers is specific and reversible and is characterized by a high affinity (Kd of 1.5 nM) and a large number of sites (1.5 x 10(6)/cell). This binding was shown to occur through noncovalent interaction with PAI-1 in the HUVEC monolayer by the fact that a monoclonal anti-PAI-1 antibody (MA-7D4) completely blocked S478A rt-PA binding. Two solution-phase assays with recombinant PAI-1 (rPAI-1) confirmed this noncovalent interaction: complexes between 125I-S478A rt-PA and rPAI-1 could be isolated by immunoprecipitation with anti-PAI-1 antibodies, and S478A rt-PA competed with rt-PA for inactivation by rPAI-1. In contrast diisopropylphosphate rt-PA (in which the active site serine is chemically modified) showed minimal binding to HUVEC monolayers, as a result of impaired interaction with PAI-1, in the two assays. Thus, both wild-type rt-PA and S478A rt-PA interact with the HUVEC monolayer through PAI-1. With rt-PA this results in the formation of covalent rt-PA.PAI-1 complexes that are released from the monolayer into the supernatant. With S478A rt-PA this results in the formation of noncovalent complexes that remain associated with the HUVEC monolayer, thereby identifying a large pool of reactive PAI-1 molecules in the monolayer. PMID- 2105931 TI - Biochemical characterization of three stimulatory GTP-binding proteins. The large and small forms of Gs and the olfactory-specific G-protein, Golf. AB - The biochemical properties of three stimulatory guanine nucleotide-binding protein (G-protein) alpha subunits, the large and small forms of Gs, Gs-l (52 kDa) and Gs-s (45 kDa), and the olfactory specific G-protein, Golf, have been compared. Complementary DNAs (cDNAs) encoding each alpha subunit were independently expressed in a mammalian cell line deficient in endogenous stimulatory G-proteins (S49 cyc-kin-). Gs-l and Gs-s respond similarly to activation by the beta-adrenergic agonist isoproterenol (EC50 = 80 and 60 nM, respectively) and the receptor-independent G-protein activators guanosine 5-O-3 (thio)triphosphate) (GTP gamma S) and AlF-4. The ability of Golf to interact with the beta-adrenergic receptor was also examined. Surprisingly, Golf interacts with beta-adrenergic receptors and is activated by isoproterenol (EC50 = 120 nM). All three G-proteins respond similarly to treatment with different alpha, beta, and gamma thiophosphoryl analogs of GTP. Specifically, (R)-GTP alpha S and GTP gamma S activate each G-protein, whereas (S)-GTP alpha S and (R)- or (S)-GTP beta S are inactive. In addition, similar to Gs alpha, Golf alpha is covalently modified and constitutively activated by cholera toxin. These studies demonstrate that all three stimulatory G-proteins are functionally and structurally similar, however, subtle differences between Golf and the two forms of Gs appear to modulate their interactions with receptors. PMID- 2105932 TI - Role of AMP on the activation of glycogen synthase and phosphorylase by adenosine, fructose, and glutamine in rat hepatocytes. AB - The mechanism for glycogen synthesis stimulation produced by adenosine, fructose, and glutamine has been investigated. We have analyzed the relationship between adenine nucleotides and glycogen metabolism rate-limiting enzymes upon hepatocyte incubation with these three compounds. In isolated hepatocytes, inhibition of AMP deaminase with erythro-9-(2-hydroxyl-3nonyl)adenine further increases the accumulation of AMP and the activation of glycogen synthase and phosphorylase by fructose. This ketose does not increase cyclic AMP or the activity of cyclic AMP dependent protein kinase. Adenosine raises AMP and ATP concentration. This nucleotide also activates glycogen synthase and phosphorylase by covalent modification. The correlation coefficient between AMP and glycogen synthase activity is 0.974. Nitrobenzylthioinosine, a transport inhibitor of adenosine, blocks (by 50%) the effect of the nucleoside on AMP formation and glycogen synthase but not on phosphorylase. 2-Chloroadenosine and N6 phenylisopropyladenosine, nonmetabolizable analogues of adenosine, activate phosphorylase (6-fold) without increasing the concentration of adenine nucleotides or the activity of glycogen synthase. Cyclic AMP is not increased by adenosine in hepatocytes from starved rats but is in cells from fed animals. [Ethylenebis (oxyethylenenitrilo)]tetraacetic acid (EGTA) blocks by 60% the activation of phosphorylase by adenosine but not that of glycogen synthase. Glutamine also increases AMP concentration and glycogen synthase and phosphorylase activities, and these effects are blocked by 6-mercaptopurine, a purine synthesis inhibitor. Neither adenosine nor glutamine increases glucose 6 phosphate. It is proposed that the observed efficient glycogen synthesis from fructose, adenosine, and glutamine is due to the generation of AMP that activates glycogen synthase probably through increases in synthase phosphatase activity. It is also concluded that the activation of phosphorylase by the above-mentioned compounds can be triggered by metabolic changes. PMID- 2105933 TI - Interaction of wild-type and catalytically inactive mutant forms of tissue-type plasminogen activator with human umbilical vein endothelial cell monolayers. AB - Several groups have demonstrated that radioiodinated tissue-type plasminogen activator (t-PA) binds to saturable sites on human umbilical vein endothelial cells (HUVECs) in culture (Hajjar, K. A., Hamel, N. M., Harpel, P. C., and Nachman, R. L. (1987) J. Clin. Invest. 80, 1712-1719; Beebe, D. P. (1987) Thromb. Res. 46, 241-254; Barnathan, E. S., Kuo, A., van der Keyl, H., McCrae, K. R., Larsen, G. L., and Cines, D. B. (1988) J. Biol. Chem. 263, 7792-7799). Here we report that most of the specific binding of 125I-t-PA to our HUVEC cultures is accounted for by binding to (i) plasminogen activator inhibitor type 1 (PAI-1), a t-PA inhibitor produced in abundance by HUVECs; and (ii) specific binding sites present on the plastic culture surface. The contribution of the sites on plastic can be eliminated by taking several precautions. Then, most or all of the specifically bound 125I-t-PA is present in a sodium dodecyl sulfate-stable 110 kDa 125I-t-PA.PAI-1 complex. Interestingly, a radioiodinated mutant form of t-PA, S478A, which is catalytically inactive and therefore unable to form the covalent complex with PAI-1, still binds to HUVECs. In fact, this ligand binds to HUVECs in 10-30-fold greater amounts than does wild-type 125I-t-PA (resulting in greater than 1 x 10(7) S478A 125I-t-PA molecules bound/cell at 12 nM ligand concentration). In contrast, diisopropyl fluorophosphate-treated t-PA binds to HUVECs in much smaller amounts than does wild-type t-PA. Several findings suggest that PAI-1 is a major binding site for S478A t-PA. The vast amount of binding observed with S478A t-PA, compared with wild-type t-PA, may be accounted for by an observed large scale release of wild-type 125I-t-PA.PAI-1 complexes from the solid phase (cells or extracellular matrix) into the culture medium. Immunoprecipitation experiments demonstrate that, in contrast to wild-type t-PA, S478A t-PA does not extract [35S]methionine-PAI antigen from metabolically labeled extracellular matrix. It is proposed that t-PA releases PAI-1 from the solid phase when it forms the irreversible covalent complex with the inhibitor, a process that does not occur with the catalytically inactive mutant form of t-PA. PMID- 2105934 TI - Expression and characterization of RNase III and Era proteins. Products of the rnc operon of Escherichia coli. AB - The synthesis rates of ribonuclease III (RNase III) and Era proteins are relatively low, and expression of the era gene is translationally coupled with expression of the rnc gene. Expression of both genes is negatively controlled by RNase III itself. We have constructed plasmids that overproduce RNase III and/or Era proteins under the control of the lambda PL promoter. A plasmid with the rnc gene under PL control expresses RNase III at levels greater than 40% of total cellular protein. Another plasmid with the era gene under PL control and a modified translation-initiation signal produces up to 80% of total cell protein as Era. Each protein has been purified using simple and rapid procedures. Purified RNase III protein specifically processes mRNA transcripts containing known RNase III sites. The purified Era protein binds GDP and GTP and has GTPase activity. Kinetic analysis shows that one molecule of GTP or GDP is bound/Era peptide with a Kd of 5.5 microM for GTP binding and 1.0 microM for GDP binding. The Km of the Era GTPase is 9.0 microM, and the maximum catalyzed rate of GTP hydrolyzed/min/mol of Era protein at 37 degrees C is 9.8 mmol. PMID- 2105935 TI - Alteration of the major phosphorylation site of eukaryotic protein synthesis initiation factor 4E prevents its association with the 48 S initiation complex. AB - Site-directed mutagenesis was used to replace the serine residue at the primary phosphorylation site of human eukaryotic initiation factor (eIF) 4E with an alanine residue. The mutated cDNA was transcribed in vitro, and the transcript was used to direct protein synthesis in a reticulocyte lysate system. The variant protein (eIF-4EAla) was retained on a 7-methylguanosine 5'-triphosphate (m7GTP) Sepharose affinity column and was specifically eluted by m7GTP. Examination of eIF-4EAla by isoelectric focusing revealed two species which had the same pI values as the phosphorylated and nonphosphorylated forms of unaltered eIF-4E (here designated eIF-4ESer). However, conversion of unphosphorylated eIF-4EAla to the putative phosphorylated eIF-4EAla in the reticulocyte lysate system was slower than the corresponding conversion of eIF-4ESer. The possibility that the more acidic form of eIF-4EAla was due to NH2-terminal acetylation was ruled out by an experiment in which the acetyl-CoA pool of the reticulocyte lysate system was depleted with oxaloacetate and citrate synthase. The more acidic form of eIF 4EAla was, however, eliminated by treatment with calf intestine alkaline phosphatase, suggesting that it results from a second-site phosphorylation. When translation reaction mixtures were resolved on sucrose density gradients, the 35S labeled eIF-4ESer was found on the 48 S initiation complex in the presence of guanylyl imidodiphosphate, as reported earlier (Hiremath, L.S., Hiremath, S.T., Rychlik, W., Joshi, S., Domier, L.L., and Rhoads, R.E. (1989) J. Biol. Chem. 264, 1132-1138). eIF-4EAla, by contrast, was not found on the 48 S complex, suggesting that phosphorylation of eIF-4E is necessary for it to carry out its role of transferring mRNA to the 48 S complex. Supporting this interpretation was the finding that eIF-4ESer isolated from 48 S initiation complexes consisted predominantly of the phosphorylated form. PMID- 2105936 TI - Signal transduction by the bacterial phosphotransferase system. Diauxie and the crr gene (J. Monod revisited). PMID- 2105937 TI - Cooperative stimulation of specific gene transcription by epidermal growth factor and transforming growth factor type beta 1. AB - Transforming growth factor type beta 1 (TGF-beta 1) is a pleiotropic regulator of cell growth and differentiation which can potentiate or otherwise modify cellular responses to different growth factors such as epidermal growth factor (EGF). Since cellular responses to peptide growth factors are mediated, in part, through the regulation of specific gene expression, we have studied the effect of TGF beta 1 on the EGF-dependent transcriptional of a diverse panel of genes which included the fibronectin gene, the cytoskeletal beta- and gamma-actin genes, and the c-fos protooncogene. The addition of a combination of TGF-beta 1 (10 ng/ml) and EGF (10 ng/ml) to quiescent AKR-2B cells maintained in serum-free medium resulted in a strong synergistic stimulation of transcription which was not evident using either growth factor individually at concentrations of 20-100 ng/ml. This effect was evident within 10 min and did not require the continual presence of TGF-beta 1 in the culture medium. Increased responsiveness of some gene promoters to EGF stimulation was evident for up to 6 h following a brief 10 min exposure to TGF-beta 1. Similar exposure to either platelet-derived growth factor or fibroblast growth factor had little or no effect on EGF-stimulated transcription. These results indicate that the transcriptional response of specific genes to EGF can be stably altered as a consequence of exposure to TGF beta 1. PMID- 2105938 TI - Spontaneous [Ca2+]i fluctuations in rat chromaffin cells do not require inositol 1,4,5-trisphosphate elevations but are generated by a caffeine- and ryanodine sensitive intracellular Ca2+ store. AB - A considerable fraction (65%) of single rat chromaffin cells loaded with the fluorescent [Ca2+]i indicator fura-2 exhibited spontaneous rhythmic fluctuations with an average period of approximately 100 s. Parallel patch clamp experiments as well as fura-2 experiments carried out in Ca2(+)-free and other modified media in the presence of Ca2+ and Na+ channel blockers indicated an origin from intracellular stores. Appropriate concentrations of agonists (bradykinin and histamine) for receptors (B2 and H1) that trigger generation of inositol 1,4,5 trisphosphate induced increased fluctuation frequency, recruitment of silent cells, and large [Ca2+]i changes at high doses. These effects were blocked by cell pretreatment with neomycin, a drug that inhibits inositol 1,4,5 trisphosphate generation. In contrast, spontaneous fluctuations and the effects of another drug, caffeine, which also induced increased frequency and recruitment, were unaffected by neomycin. Ryanodine caused first a prolongation and then (approximately 10 min) a block of both spontaneous fluctuations and caffeine effects, where the single transients after bradykinin and histamine were maintained. Caffeine and ryanodine are known to affect selectively the process of calcium-induced Ca2+ release; this is the first demonstration of [Ca2+]i fluctuation activity arising from Ca2(+)-induced Ca2+ release in nonmuscle cells with no strict requirement for inositol 1,4,5-trisphosphate involvement. PMID- 2105940 TI - Secretion of sulfated and nonsulfated forms of parathyroid chromogranin A (secretory protein-I). AB - Chromogranin A (secretory protein-I) is an acidic, sulfated glycoprotein found in secretory granules of most endocrine cells but not in exocrine or epithelial cells. Parathyroid chromogranin A is sulfated on tyrosine residues, whereas adrenal chromogranin A appears to be sulfated mainly on oligosaccharide residues. Chromogranin B, on the other hand, is tyrosine-sulfated in the bovine adrenal whereas this protein is absent from the parathyroid. The role of this tissue- or species-specific sulfation of chromogranin is not known. Tyrosine sulfation is a common post-translational modification of proteins in the exocytotic pathway and has been suggested to play a role in the sorting or intracellular transport of secretory proteins. To test this, porcine parathyroid tissue slices were metabolically labeled with 35SO4 and [3H]Lys, and the tissue and incubation medium analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and immunoprecipitation with chromogranin A-specific antiserum or by radioimmunoassay for parathormone. Secretion of total and 3H-labeled chromogranin A was about 3- and 7-fold higher, respectively, at 0.5 mM than at 3.0 mM Ca2+, and secretion of 35SO4-labeled chromogranin A was 67-fold higher. This indicates that either sulfated chromogranin A is directed primarily to the Ca2+-regulated pathway or that sulfation occurs following sorting to this pathway. Sodium chlorate (1-10 mM) inhibited sulfation in a dose-dependent manner by up to 95% but it had no effect on the onset or rate of chromogranin A secretion. These data indicate that regulated secretion of parathyroid chromogranin A does not require sulfation of tyrosine residues. PMID- 2105939 TI - Interleukin 1 inhibits T cell receptor-mediated apoptosis in immature thymocytes. AB - T cell receptor signaling has been implicated in an intrathymic process of cell selection in which potentially harmful autoreactive precursors are deleted before they emigrate to the periphery. Recent work has shown that immature thymocytes undergo apoptosis, or programmed cell death, upon stimulation via the T cell antigen receptor, and it has been suggested that this mechanism may mediate deletion of the self-reactive clones during T cell development. Here we report that the accessory cell-derived T cell growth hormone interleukin-1 prevents T cell receptor-mediated thymocyte apoptosis by a mechanism that appears to involve protein kinase C activation. This effect may be relevant to the positive signaling that spares the appropriate precursors during the generation of functional T lymphocytes. PMID- 2105941 TI - Nucleotide analogue inhibitors of purine nucleoside phosphorylase. AB - The diphosphate of the antiherpetic agent acyclovir [9-[(2 hydroxyethoxy)methyl]guanine] has been shown to inhibit purine nucleoside phosphorylase with unique potency (Tuttle, J. V., and Krenitsky, T. A. (1984) J. Biol. Chem. 259, 4065-4069). A major factor contributing to the superior inhibition by this diphosphate over the corresponding mono- and triphosphates is revealed here. Homologues of acyclovir mono- and diphosphate that extend the ethoxy moiety by one to four methylene groups were synthesized. These homologues were evaluated for their ability to inhibit human purine nucleoside phosphorylase. Within the diphosphate series, the Ki values increased progressively with increasing chain length. With the monophosphates, the Ki values reached a minimum with the homologue containing a pentoxy moiety. A plot of chain length versus Ki values for both mono- and diphosphates showed that both series had similar optimal distances between the aminal carbon and the terminal oxygen anion. Monophosphates with optimal positioning were somewhat less potent than diphosphates with similar positioning. Nevertheless, it was clear that a major factor in determining potency of inhibition was the distance of the terminal phosphate from the guanine moiety. PMID- 2105942 TI - Differential degradation rates of the G protein alpha o in cultured cardiac and pituitary cells. AB - Signal transduction in biological membranes is modulated by a family of GTP binding proteins termed G proteins. Differences in the tissue-specific expression of G protein subtypes suggest that the levels of individual G proteins may be an important determinant of the hormonal response in a given cell type. We have used a polyclonal antibody raised against the purified G protein, alpha o to study alpha o in the rat pituitary cell line GH4 and in primary rat cardiocytes in culture by quantitative immunoprecipitation. Biosynthetic labeling and specific immunoprecipitation of alpha o in pulse-chase experiments demonstrated that the t1/2 for alpha o degradation is 28 +/- 7 h (n = 4) in GH4 pituitary cells and is greater than 72 h (n = 4) in cardiocytes. The steady-state level of alpha o protein is similar in both cell types as measured by Western blots. Northern blots of poly(A)-selected mRNA from these two cell types were probed with labeled alpha o cDNA and showed they have similar alpha o mRNA levels. The observation of different degradation rates, but similar steady-state protein levels, suggests that the rate of alpha o synthesis is different in GH4 cells and cardiocytes. Since mRNA levels are approximately equal in both, our studies imply that protein translation controls may be important determinants of G protein alpha subunit concentrations in biological membranes. PMID- 2105943 TI - Characterization of a transferrin-independent uptake system for iron in HeLa cells. AB - HeLa cells incubated in serum-free medium accumulated 59Fe ("non-transferrin iron") when incubated with either 59Fe-citrate, 59Fe-nitrilotriacetate, or 59Fe dissolved in Tricine ascorbate. Accumulation of iron was time-, concentration-, and Ca2+-dependent and was saturable. Uptake of non-transferrin (non-Tf) iron was transferrin-independent because of the fact that uptake occurred at pH 5.5, a pH at which transferrin binds iron poorly and at which transferrin is not internalized by cells. Uptake of non-Tf iron was less affected than uptake of transferrin iron by 1) exposure of cells to trypsin, a maneuver that cleaves Tf receptors, or 2) incubation of cells with phenylarsine oxide, an agent that inhibits both fluid- and receptor-mediated internalization. After exposure of cells to non-Tf iron at 37 degrees C, most of the cell-associated radioactivity was recovered in heme and ferritin, demonstrating that iron gained access to intracellular compartments and was not simply adsorbed to the cell surface. Uptake of non-Tf iron could be partially blocked by Cu2+ in a dose-dependent manner, while the accumulation of transferrin-bound iron was unaffected by Cu2+. Other transition metals, such as Zn2+, Cd2+, and Mn2+ were able to inhibit the uptake of non-Tf iron to different degrees. The accumulation of 109Cd was inhibited by incubation of cells with non-Tf iron, Cu2+, or Mn2+. The extent of inhibition was concentration- and metal-dependent. A number of cultured cell lines including HeLa, human skin fibroblasts, and Chinese hamster ovary cells demonstrated uptake of non-Tf iron and 109Cd. Additionally, an endosome acidification mutant of Chinese hamster ovary cells, which exhibited an increase in non-Tf iron uptake, also exhibited an increase in the uptake of Cd2+. These observations suggest that the characteristics of the non-Tf iron transport system in HeLa cells are similar if not identical to those reported for perfused rat liver (Wright, T. L., Brissot, P., Ma, W.-L., and Weisiger, P. A. (1986) J. Biol. Chem. 261, 10909-10914) and suggest the existence of a family of transition metal transport systems, each with a different metal specificity. PMID- 2105944 TI - Sensitivity of efflux-driven carrier turnover to external pH in mutants of the Escherichia coli lactose carrier that have tyrosine or phenylalanine substituted for histidine-322. A comparison of lactose and melibiose. AB - Two Escherichia coli lactose carrier mutants (tyrosine or phenylalanine substituted for histidine 322) were studied under conditions of net efflux or equilibrium exchange. Net lactose efflux by either mutant was 10-20-fold slower than by the parent and was sensitive to extracellular pH (5.6-8.0). The presence of extracellular lactose (equilibrium exchange) failed to accelerate loss of [14C]lactose, indicating that the step(s) rate limiting for exchange were also rate limiting for net lactose efflux. Net melibiose efflux by the Phe-322 mutant was comparable to the normal carrier, while that by the Tyr-322 mutant was 5-fold faster (pH 7.0). Melibiose efflux by either mutant was sensitive to pH (5.6-8.0). Melibiose in the extracellular medium significantly accelerated loss of [3H]melibiose from either mutant, showing that slow exchange is a sugar-specific phenomenon and not an intrinsic property of these mutants. The sugar-specific effect of these mutations could mean that the defect in these mutants is not on the path of the proton, although alternative explanations cannot as yet be eliminated. The modest effect of these mutations on the transport rate indicates that His-322 contributes a far smaller free energy increment to catalyzing of H+/galactoside cotransport than active site histidines contribute to catalyzing peptide bond hydrolysis in serine proteases. We interpret this to mean that in chemical terms the function of these catalytic histidine residues differ considerably. PMID- 2105945 TI - The mitotic apparatus-associated 51-kDa protein from sea urchin eggs is a GTP binding protein and is immunologically related to yeast polypeptide elongation factor 1 alpha. AB - We investigated the biochemical characteristics of the 51-kDa protein that is a major mitotic apparatus-associated basic protein of sea urchin eggs (Toriyama, M., Ohta, K., Endo, S., and Sakai, H. (1988) Cell Motil. Cytoskeleton 9, 117 128). The amino acid composition of the 51-kDa protein was apparently different from those of tubulin, actin, histones, and myelin basic protein; yet it was similar to those of polypeptide elongation factors 1 alpha (EF-1 alpha). In addition, antibody to EF-1 alpha from yeast cross-reacted with the 51-kDa protein. [3H] GTP binding activity was detected in the phosphocellulose-purified fraction (PC fraction) which predominantly contained the 51-kDa protein and was shown to be specific to GTP, GDP, guanylyl imidodiphosphate, and ITP. Photo affinity labeling using [alpha-32P]8-azidoguanosine triphosphate (8-azido-GTP) demonstrated that a 51-kDa polypeptide in the PC fraction specifically bound 8 azido-GTP. This GTP-binding polypeptide was bound to a GTP affinity column, could be eluted by the addition of GTP, and was immunoreactive with anti-51-kDa protein antibodies. When the PC fraction was applied to a gel filtration chromatography column, GTP binding activity was completely coeluted with the 51-kDa protein. Furthermore, the PC fraction and the gel filtration-purified fraction had EF-1 alpha activity: [14C]Phe-tRNA transferring activity to ribosomes in the presence of poly(U) and ribosome-dependent GTPase activity. The results indicate that the mitotic apparatus-associated 51-kDa protein is a GTP-binding protein and suggest that it is structurally and functionally related to yeast EF-1 alpha. PMID- 2105946 TI - Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells. AB - AP-1, the polypeptide product of c-jun, recognizes and binds to specific DNA sequences and stimulates transcription of genes responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). We studied the effects of TPA on the regulation of c-jun gene expression in HL-60 cells during monocytic differentiation. Low levels of c-jun transcripts were detectable in untreated HL-60 leukemic cells, increased significantly by 6 h, and reached near maximal levels by 24 h of exposure to 32 nM TPA. Similar kinetics of c-jun induction by TPA were observed in human U-937 and THP-1 monocytic leukemia cells. Similar findings were obtained with bryostatin 1 (10 nM), another activator of protein kinase C and inducer of monocytic differentiation. Furthermore, 1,25-dihydroxyvitamin D3 (0.5 microM), a structurally distinct agent which also induces HL-60 monocytic differentiation, increased c-jun expression. TPA treatment of HL-60 cells in the presence of cycloheximide was associated with superinduction of c-jun transcripts. Run-on analysis demonstrated detectable levels of c-jun gene transcription in untreated HL-60 cells, and that exposure to TPA increases this rate 3.3-fold. Treatment of HL-60 cells with both TPA and cycloheximide had no effect on the rates of c-jun transcription. The half-life of c-jun RNA as determined by treating HL-60 cells with TPA and actinomycin D was 30 min. In contrast, the half-life of c-jun RNA in TPA-treated HL-60 cells exposed to cycloheximide and actinomycin D was greater than 2 h. These findings suggested that the increase in c-jun RNA observed during TPA-induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms. PMID- 2105947 TI - Bovine beta 1----4-galactosyltransferase: two sets of mRNA transcripts encode two forms of the protein with different amino-terminal domains. In vitro translation experiments demonstrate that both the short and the long forms of the enzyme are type II membrane-bound glycoproteins. AB - We have used S1 and primer extension analysis to demonstrate that the gene for bovine beta 1----4-galactosyltransferase specifies two sets of mRNA transcripts of different lengths. The longer mRNA transcripts initiate upstream of two in frame ATG codons and encode a protein of 402 amino acids (long form). The shorter mRNA transcripts initiate between the two in-frame ATG codons and encode a protein of 389 amino acids (short form). These two related forms of beta 1----4 galactosyltransferase have an identical large (358 amino acids), potentially glycosylated, COOH-terminal catalytic domain, and an identical single transmembrane domain. The only difference in primary structure between the two forms is that the long form contains an NH2-terminal extension of 13 amino acids. Thus, bovine beta 1----4-galactosyltransferase fits the pattern established for murine beta 1----4-galactosyltransferase (Shaper, N. L., Hollis, G. L., Douglas, J. G., Kirsch, I. R., and Shaper, J. H. (1988) J. Biol. Chem. 263, 10420-10428). Inspection of the NH2-terminal domain suggests that the long form of the bovine enzyme, like its murine counterpart, has a functional cleavable signal sequence which would dictate that the two forms of the membrane-bound enzyme are oriented in opposite directions. We have tested this hypothesis by in vitro translation in the absence or presence of dog pancreas microsomes. In vitro translation of RNA transcripts for the long and short form of beta 1----4-galactosyltransferase in the absence of microsomes results in the synthesis of polypeptides with apparent Mr of 44,500 and 43,000, respectively. In vitro translation of each transcript in the presence of microsomes results in the synthesis of two glycosylated, endoglycosidase H-sensitive proteins with apparent Mr of 47,500 and 46,000. These experiments and additional protease protection experiments demonstrate that the COOH-terminal domain of both the short and the long form of bovine beta 1----4 galactosyltransferase are translocated into the microsomal lumen. By extrapolation, both forms of the enzyme are oriented in vivo as Type II membrane bound glycoproteins. PMID- 2105948 TI - Multisite phosphorylation of the epidermal growth factor receptor. Use of site directed mutagenesis to examine the role of serine/threonine phosphorylation. AB - The major sites of serine and threonine phosphorylation of the human epidermal growth factor (EGF) receptor observed in intact cells are Thr654, Thr669, Ser1046, and Ser1047. Phosphorylation of the EGF receptor is increased at these sites in cells treated with platelet-derived growth factor or phorbol ester. This increase in EGF receptor phosphorylation is associated with an inhibition of the high affinity binding of EGF to cell surface receptors and an inhibition of the receptor tyrosine protein kinase activity. In order to test the hypothesis that the phosphorylation of the EGF receptor is mechanistically related to the modulation of EGF receptor function, we replaced the major sites of serine and threonine phosphorylation with alanine residues. EGF receptors containing single point mutations or multiple mutations were expressed in Chinese hamster ovary cells. Analysis of the regulation of the EGF receptor tyrosine protein kinase activity demonstrated that phorbol ester caused an inhibition of the tyrosine phosphorylation of wild-type receptors and receptors lacking Thr669, Ser1046, or Ser1047. In contrast, the inhibition of EGF receptor tyrosine phosphorylation caused by phorbol ester was not observed for any of the mutated EGF receptors that lacked Thr654. These data are consistent with the hypothesis that the phosphorylation of the EGF receptor at Thr654 is required for the inhibition of the receptor tyrosine protein kinase activity caused by phorbol ester. Investigation of the apparent affinity of the EGF receptor demonstrated that treatment with phorbol ester caused an inhibition of the high affinity binding of 125I-EGF to cells expressing wild-type EGF receptors and each of the mutated EGF receptors examined. We conclude that the regulation of the apparent affinity of the EGF receptor is independent of the major sites of serine and threonine phosphorylation of the EGF receptor. PMID- 2105949 TI - Expression of chimeric cDNAs in cell culture defines a region of UDP glucuronosyltransferase involved in substrate selection. AB - The cDNAs encoding two forms of UDP glucuronosyltransferase have been expressed in cultured cells to demonstrate that one form, UDPGTr-3, glucuronidates testosterone, whereas the second form, UDPGTr-4, is mainly active toward etiocholanolone (Mackenzie, P. I. (1986) J. Biol. Chem. 261, 14112-14117; Mackenzie, P. I. (1987) J. Biol. Chem. 262, 9744-9749). In order to localize areas of the polypeptide chain involved in substrate selection, the 5' regions of UDPGTr-3 and -4 cDNAs were exchanged to form two chimeric cDNAs. A 53-kDa protein was synthesized in COS cells transfected with the chimeric UDPGTr-3.4 cDNA, which encodes the amino-terminal 298 residues of UDPGTr-3 and the carboxyl-terminal 232 residues of UDPGTr-4. This protein glucuronidated testosterone rather than etiocholanolone and had a faster electrophoretic mobility when transfected COS cells were cultured in the presence of tunicamycin, an inhibitor of N-linked glycosylation. The unglycosylated variant produced by this treatment also glucuronidated testosterone. In contrast, a 50-kDa protein that was more active toward etiocholanolone as substrate was synthesized in COS cells transfected with UDPGTr-4.3, a chimeric cDNA that encodes the amino-terminal region of UDPGTr-4 joined to the carboxyl-terminal region of UDPGTr-3. The electrophoretic mobility of this chimeric protein was unaffected by tunicamycin treatment. These results demonstrate that amino acid sequences that specify substrate specificity are localized in the amino-terminal half of the UDP glucuronosyltransferase polypeptide chain and that the presence of N-linked oligosaccharide chains on the protein does not affect the choice of substrate. PMID- 2105950 TI - Stretching cardiac myocytes stimulates protooncogene expression. AB - Recently cellular protooncogenes have been found to be induced as an early response to pressure overload in cardiac hypertrophy. To examine whether mechanical stimuli directly induce specific gene expression in the heart, we cultured rat neonatal cardiocytes in elastic silicone dishes and stretched these adherent cells. Myocyte stretching stimulated expression of the protooncogene, c fos, in a stretch length-dependent manner, followed by an increase in amino acid incorporation into proteins. c-fos mRNA levels were enhanced within 15 min by cardiocyte stretching, peaked at 30 min, and declined to undetectable levels by 240 min. In the presence of cycloheximide, a greater increase in c-fos mRNA was seen by stretching. The transfected chloramphenicol acetyltransferase gene linked to upstream sequences of the fos gene including its promoter was also activated by stretching cardiac myocytes. These results suggest that mechanical loading directly regulates gene transcription without the participation of humoral factors in cardiocytes. PMID- 2105951 TI - Sequence analysis of bovine lens aldose reductase. AB - The covalent structure of bovine lens aldose reductase (alditol-NADP+ oxidoreductase, EC 1.1.1.21) was determined by sequence analysis of peptides generated by specific and chemical cleavage of the homogeneous apoenzyme. Peptides, purified by reverse-phase high performance liquid chromatography were subjected to compositional analysis and sequencing by gas-phase automated Edman degradation. Aldose reductase was found to contain 315 amino acid residues. The enzyme is blocked at the amino terminus, and mass spectrometry was employed to identify the blocking acetyl group and to sequence the amino-terminal tryptic peptide. The aldose reductase was shown to contain no carbohydrate despite the fact that the enzyme contains the consensus sequence -Asn-Lys-Thr- for N-linked glycosylation. Comparative sequence analysis and application of algorithms for prediction of secondary structure and nucleotide binding domains are consistent with the view that aldose reductase is a double-domain protein with a beta-alpha beta secondary structural organization. The NADPH binding site appears to be associated with the amino-terminal half of the enzyme. Modeling studies based on the tertiary structures of dihydrofolate and glutathione reductases indicate that the NADPH binding site begins at Lys-11 and continues with a beta-alpha-beta fold characteristic of nucleotide binding proteins. PMID- 2105952 TI - Mitogenic signaling by epidermal growth factor (EGF), but not platelet-derived growth factor, requires arachidonic acid metabolism in BALB/c 3T3 cells. Modulation of EGF-dependent c-myc expression by prostaglandins. AB - Previously, we have shown that prostaglandins are necessary, but not sufficient, for the stimulation of mitogenesis in BALB/c 3T3 fibroblasts by epidermal growth factor (EGF) (Nolan, R. D., Danilowicz, R. M., and Eling, T. E. (1988) Mol. Pharmacol. 33, 650-656). The purpose of this work was to extend these findings to another potent mitogen, platelet-derived growth factor (PDGF), and to determine if metabolism of arachidonic acid to prostaglandins is necessary for stimulation of expression of the protooncogene c-myc by EGF, which is an early event in the mitogenic cascade. In BALB/c 3T3 cells grown to about 70% confluence and deprived of serum for 16-24 h, PDGF stimulated [3H]thymidine uptake into DNA significantly in a concentration-dependent manner, but did not increase production of prostaglandin E2 (PGE2). The addition of indomethacin, a prostaglandin H synthase inhibitor, or nordihydroguaiaretic acid, a lipoxygenase inhibitor, did not affect PDGF-stimulated thymidine uptake into DNA. In addition, PGE2 enhanced EGF dependent, but not PDGF-dependent, mitogenesis. Taken together, the data support the hypothesis that prostaglandins are not involved in PDGF-dependent mitogenesis. In contrast, indomethacin (10(-6) M) and nordihydroguaiaretic acid (10(-6) M) inhibited EGF-stimulated thymidine uptake and c-myc expression by approximately 50%. Addition of PGG2 (10(-7) to 10(-5) M) in the presence of indomethacin and EGF restored the ability of EGF to elevate c-myc RNA levels and DNA synthesis. When PGF2 alpha (10(-8) to 10(-5) M) was added in the presence of EGF, c-myc RNA levels and thymidine incorporation were elevated up to 5-6-fold above levels observed with EGF alone. These data support the hypothesis that metabolism of arachidonic acid to prostaglandins is necessary for stimulation of c-myc expression by EGF in BALB/c 3T3 cells. PMID- 2105953 TI - Inhibition of IgA1 proteinases from Neisseria gonorrhoeae and Hemophilus influenzae by peptide prolyl boronic acids. AB - The alpha-aminoboronic acid analog of proline has been synthesized and incorporated into a number of peptides as the COOH-terminal residue. These peptide prolyl boronic acids are potent inhibitors of both the type 1 and type 2 IgA proteinases from Neisseria gonorrhoeae and Hemophilus influenzae, but not of the functionally similar IgA proteinase from Streptococcus sanguis. The best inhibitors synthesized thus far have Ki values in the nanomolar range (4.0 to 60 nM). These results indicate that the N. gonorrhoeae and the H. influenzae enzymes belong to the serine protease family of proteolytic enzymes while that from S. sanguis does not. As a group, the IgA proteinases have been noted for their remarkable specificity; thus, the peptide prolyl boronic acids reported here are the first small synthetic molecules to exhibit a relatively high affinity for the active site of an IgA proteinase and are therefore the first to yield some insight into the active site structure and specificity requirements of these enzymes. PMID- 2105954 TI - Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. AB - Assembly of the terminal complement proteins C5b-9 on human endothelial cells results in increased cytosolic calcium and nonlytic secretion of high molecular weight multimers of von Willebrand factor from intracellular storage granules. We now demonstrate that this C5b-9-induced secretory response is accompanied by vesiculation of membrane particles from the endothelial surface which express binding sites for factor Va and support prothrombinase activity. Exposure of factor Va binding sites after C5b-9 assembly was accompanied by greater than 2 fold increase in prothrombinase activity, which was not observed for cells exposed to C5b-8 (in the absence of C9). By contrast, only a 3-16% increase in prothrombinase activity was observed when these cells were maximally stimulated to secrete by either histamine, thrombin, or the Ca2+ ionophore A23187. Increased prothrombinase activity after C5b-9 was not accompanied by a change in thrombomodulin activity, and was unrelated to cell lysis, the complement-treated cells remaining greater than 99% viable. Endothelial prothrombinase activity was predominately associated with small membrane vesicles (less than 1 microns diameter) released from the cell monolayer. Analysis by fluorescence-gated flow cytometry revealed that these vesicles incorporate the C5b-9 proteins and express binding sites for factor Va. The capacity of the C5b-9 proteins to induce vesiculation of the endothelial plasma membrane and thereby expose catalytic surface for the prothrombinase enzyme complex may contribute to fibrin deposition associated with immune endothelial injury. PMID- 2105955 TI - Ligand interactions with the kringle 5 domain of plasminogen. A study by 1H NMR spectroscopy. AB - The binding of small molecules to the kringle 5 domain fragment of human plasminogen has been investigated by 1H NMR spectroscopy at 300 MHz. The compounds tested as potential ligands include L-arginine, L-lysine, and a number of aliphatic and aromatic analogs of similar size but different ionic charge configurations. Ligand/kringle 5 association constant (Ka) values were obtained from ligand titration experiments at 22 degrees C, pH 7.2. Neither L-arginine nor N alpha-acetyl-L-arginine and N alpha-acetyl-L-arginine methyl ester bind measurably to kringle 5 (Ka approximately less than 0.05 mM-1). In contrast, binding of hexylamine or epsilon-aminocaproic acid (epsilon ACA) is favored (Ka approximately 2.9 and 10.5 mM-1, respectively). Benzamidine and p benzylaminesulfonic acid associate with kringle 5 with similar affinities (Ka approximately 3.4 and 2.2 mM-1, respectively) while benzylamine binds about twice as tightly (Ka approximately 6.3 mM-1). The higher affinities toward both benzylamine and epsilon ACA indicate that a free carboxylate group is not, by itself, a main determinant of ligand-binding to kringle 5. The experiments also reveal a definite affinity for L-arginine methyl ester, L-lysine, and N alpha acetyl-L-lysine methyl ester. It is suggested that, although weak (0.1 approximately less than Ka approximately less than 0.6 mM-1), these interactions could be of physiological relevance in the context of plasminogen binding to the fibrin clot. Ligand-induced shifts of kringle 5 proton resonances indicate that the Trp25, His33, Tyr50, Trp62, and Tyr72 (kringle numbering convention) side chains form or neighbor the kringle 5-binding site. Benzamidine-kringle 5 magnetization transfer (Overhauser) experiments verify a close proximity of the bound ligand to these aromatic groups. A model of the binding site is proposed in which the above residues interact closely with each other and define a lipophilic surface which is accessible to the free ligand. PMID- 2105956 TI - Transport of basic amino acids by the dinitrogen-fixing cyanobacterium Anabaena PCC 7120. AB - Two transport systems for L-arginine were evident in Anabaena sp. strain PCC 7120: a high-affinity one (Km, 1.7 microM) that accumulated arginine within the cells through an energy-requiring process and another one that exhibited low affinity for L-arginine (Km, 0.75 mM) and was unable to accumulate the substrate. Both systems were inhibited by L-canavanine, L-lysine, and L-ornithine. Two systems were also evident for L-lysine uptake (Km, 1.9 and 110 microM, respectively). After selection for resistance to canavanine or hydroxylysine, independent mutants were isolated which were impaired in the high-affinity uptake of arginine and lysine. A common permease appears, therefore, to be involved in the high-affinity transport of these basic amino acids. Both the high- and the low-affinity systems can contribute to the growth of Anabaena sp. on L-arginine. However, arginine did not effectively repress either nitrogenase or nitrate reductase. PMID- 2105957 TI - Regulation of ornithine decarboxylase expression by anisosmotic shock in alpha difluoromethylornithine-resistant L1210 cells. AB - Ornithine decarboxylase (ODC) activity is known to be strongly enhanced in mammalian cells by a sudden reduction in ambient osmolality. The effect of hypoosmotic shock on the regulation of ODC protein and mRNA levels was studied in a variant L1210 mouse leukemia cell line (D-R cells) which expresses ODC at greater than or equal to 100-fold higher levels than the parental cells. Hypoosmotic stress increased ODC activity in proportion with the osmotic gradient imposed to both D-R cells and their normal counterparts. A 60% decrease in medium osmolality increased ODC activity and the amount of immunoreactive ODC protein from 20- to 30-fold after 4 h without any detectable change in ODC mRNA contents in D-R cells. ODC induction was sustained up to 48 h after hypoosmotic shock, with maximal activity levels being observed at 24 h. Hypotonic shock dramatically increased (up to 36-fold) the rate of ODC synthesis as measured by 10-min pulses with 35S-labeled methionine, in agreement with kinetic constants predicted from the changes observed for the enzyme activity. Moreover, hypoosmotic stress extended the half-life of ODC activity from 35 +/- 10 to 212 +/- 67 min and blocked any degradation of the radiolabeled immunoreactive protein, which had a half-life of 28 +/- 6 min under isotonic conditions, for at least 120 min after addition of cycloheximide. The induction of ODC by hypoosmotic stress was quickly reversed by a sudden upshift of osmolality through a very rapid inhibition of ODC biosynthesis and an increase in the rate of enzyme degradation. Thus, hypoosmotic stress activates the expression of ODC exclusively through post-transcriptional mechanisms in D-R cells. The osmotically induced accumulation of ODC molecules is quite unique as shown by the fact that ODC is the major protein (approximately 25% of total) synthesized during the first 4 h following a 60% hypotonic shock, despite a 30-50% reduction of the rate of labeled precursor incorporation into soluble proteins. PMID- 2105958 TI - Reconstitution of protein translocation activity from partially solubilized microsomal vesicles. AB - We have used a reconstitution assay to demonstrate that protein translocation activity can be recovered after microsomal vesicles derived from the rough endoplasmic reticulum have been partially solubilized with n-octyl-beta glucopyranoside. Two independent approaches were used to establish conditions for partially solubilizing microsomal membranes. When the lipid bilayer was disrupted by detergents to the extent that the integrity of the lipid bilayer had been perturbed, membranes were inactive for translocation. However, detergent-treated membranes could be reconstituted in good yield into a translocation competent form once the detergent was removed. PMID- 2105959 TI - Localization of the high molecular weight kininogen binding site in the heavy chain of human factor XI to amino acids phenylalanine 56 through serine 86. AB - We have previously demonstrated that a monoclonal antibody (5F7) directed against the heavy chain region of factor XI inhibits the binding of factor XI to high molecular weight kininogen (high Mr kininogen) and the surface-mediated proteolytic activation of factor XI by factor XIIa in the presence of high Mr kininogen. In order to identify the structural domain of factor XI that binds high Mr kininogen, CNBr-digested factor XI was passed over a 5F7 antibody affinity column. One of two CNBr peptides that bound to this 5F7 affinity column inhibited binding of 125I-factor XI to high Mr kininogen, as did intact factor XI. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate of an inhibitory peptide purified by high performance liquid chromatography revealed an Mr of 10,000-15,000. Gas-phase sequencing of this peptide revealed the following amino terminal sequence: X-X-Val-Thr-Gln-Leu-Leu-Lys-Asp-Thr. These data together with the amino acid composition of the isolated peptide indicate that both the epitope recognized by antibody 5F7 and at least a portion of the high Mr kininogen binding site are contained within the amino-terminal portion of factor XI comprising residues Glu-1 through Met-102. Further cleavage of this peptide with o-iodosobenzoic acid at a tryptophanyl peptide bond revealed that an Mr 5,000 peptide (with the amino-terminal sequence Trp-Phe-Thr-Cys-Val-Leu) bound to a high Mr kininogen affinity column and inhibited binding of 125I-factor XI to high Mr kininogen. Finally, a synthetic peptide comprising residues Phe-56 through Ser 86 inhibited 125I-factor XI binding to high Mr kininogen. These experiments strongly suggest that the high Mr kininogen binding site is contained within the domain in the heavy chain region of factor XI comprising residues Phe-56 through Ser-86. PMID- 2105961 TI - Immobilization and characterization of beta-galactosidase in thermally reversible hydrogel beads. AB - Beta-Galactosidase has been immobilized within thermally reversible hydrogel beads and has been studied in batch and packed bed reactor systems. The enzyme was entrapped in a copolymer hydrogel of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) as beads were formed in an inverse suspension polymerization. A reversible deswelling and reswelling of the hydrogel matrix was induced by first warming and then cooling through 37-40 degrees C, which is the lower critical solution temperature, LCST, of the backbone copolymer. The optimum temperature for maximum activity of the immobilized enzyme-gel bead system was found to be 30 35 degrees C in a batch mode and 40 degrees C in a packed bed reactor, which were both below the 50 degrees C optimum for the free enzyme. These differences are understandable, since the mass transfer rates of substrate and product within the pores of the gel matrix are controlled mainly by the temperature, so therefore it is the temperature which governs the overall activity of the immobilized enzyme system. It was also found that when the operational temperature in the packed bed reactor was cycled between temperatures below (35 degrees C) and above (45 degrees C) the copolymer gel LCST, the activity of the immobilized enzyme almost fully recovered after each cycle. In fact, the enzyme-gel system exhibited a complete "shut-off" in activity at 50 degrees C which was the temperature where the free enzyme showed its maximum activity. The thermal cycling operation of LCST enzyme-gel beads can be used to enhance overall activity and productivity of a packed bed reactor, when compared to isothermal operation of this reactor. This is due to the thermally induced "pumping" which enhances mass transfer rates of substrate in and product out of the gel beads. PMID- 2105960 TI - Phosphorylation of the amino-terminal head domain of the middle molecular mass 145-kDa subunit of neurofilaments. Evidence for regulation by second messenger dependent protein kinases. AB - To begin to understand the regulation and roles of neurofilament phosphorylation, we localized the phosphorylated domains on the 140-145-kDa neurofilament subunit (NF-M) and identified the protein kinases that may specifically phosphorylate the sites within these domains in vivo. Mouse retinal ganglion cells were labeled in vivo by injecting mice intravitreally with [32P]orthophosphate, and neurofilament enriched fractions were obtained from the optic axons. Two-dimensional phosphopeptide map analysis of NF-M after digestion with alpha-chymotrypsin and trypsin revealed seven major (M8-M14) and at least eight minor (M1-M7 and M15) phosphopeptides. Two-dimensional phosphopeptide map analyses of NF-M phosphorylated in vitro by individual purified or endogenous axonal cytoskeleton associated protein kinases showed that five peptides (M9-M13) were substrates for the heparin-sensitive second messenger-independent protein kinase(s). Protein kinase A and/or protein kinase C phosphorylated eight other peptides (M1-M8). Two alpha-chymotryptic peptides (C1 and C2) that were phosphorylated by protein kinase A but not by the endogenous independent kinase(s) were isolated by high performance liquid chromatography on a reverse-phase C8 column. Partial sequence analysis of peptides C1 (S R V S G P S ...) and C2 (S R G S P S T V S ...) showed that the peptides were localized on the head domain of NF-M at 25 and 41 residues from the amino terminus, respectively. Tryptic digest of peptide C1 (less than 12 kDa) generated the phosphopeptides M1-M6. Peptide C2 was a breakdown product of peptide C1. Since the polypeptide sites targeted by second messenger-independent kinase(s) associated with neurofilaments are localized on the carboxyl-terminal domain, separate aspects of NF-M function appear to be regulated by separate kinase systems that selectively phosphorylate head or tail domains of the polypeptide. PMID- 2105962 TI - Exclusion of uropathogen adhesion to polymer surfaces by Lactobacillus acidophilus. AB - The ability of bacteria to adhere to surfaces is a major cause of concern in the use of biomaterial substrates. The adhesion of Staphylococcus epidermidis strain 1938 was examined using image analysis and was found not to correlate with polymer surface tension, unlike that of Lactobacillus acidophilus, which adhered to more hydrophobic polymers. A fimbriated uropathogenic E. coli strain showed very low levels of adherence to the biomaterials. Precoating the polymers with lactobacilli significantly reduced the staphylococcal and E. coli adhesion, a result which could have clinical significance. An additional finding was that the interaction of staphylococci and E. coli with lactobacilli coated polymers altered the adhesion profile of the latter. Lactobacilli appeared to detach from polymers of low surface tension and reattach to polymers with high surface tensions. This resulted in the highest levels of exclusion of uropathogens being found for lactobacilli-coated glass and sulfonated polystyrene, both of which are hydrophilic (with high surface tensions). These results demonstrate that lactobacilli can be used to coat biomaterial surfaces leading to a reduced adhesion of uropathogens. PMID- 2105963 TI - Prophylaxis with indomethacin for heterotopic bone. After open reduction of fractures of the acetabulum. AB - Forty-four fractures of the acetabulum that had been treated with open reduction and internal fixation necessitating dissection of the gluteal muscles were reviewed radiographically for the development of heterotopic bone. Grade-2 (Brooker classification) or more severe heterotopic ossification was seen in thirteen (50 per cent) of twenty-six patients who did not receive indomethacin but in only one (5.5 per cent) of eighteen patients who received indomethacin for six weeks postoperatively. In the patients who did not receive indomethacin, the maximum amount and extent of the heterotopic bone was evident in twelve weeks. In the patients who did receive indomethacin, the heterotopic ossification did not progress after the administration of indomethacin was discontinued. We concluded that, in patients who have a fracture of the acetabulum, indomethacin provides effective prophylaxis for heterotopic bone after operative reduction with gluteal dissection. PMID- 2105964 TI - c-fos reduces growth factor requirements for mitogenic stimulation of L6 rat myoblasts. AB - Addition of fetal calf serum (FCS) to serum-deprived L6J1 rat myoblasts increases fos-like immunoreactivity. The nuclear immunoreactivity reached a maximum 2 h after serum addition. Effects of the c-fos protein on myoblast proliferation were analyzed in L6J1 rat myoblasts transfected with the murine c-fos gene under control of a metallothionein promoter. L6J1 myoblasts with elevated expression of transfected c-fos reached higher cell densities than neo transfected control myoblasts when approaching a stationary phase in normal culture conditions (5% FCS). The differences in cell densities were even more pronounced at low serum concentrations (0.5% FCS). c-fos transfected cells also had a faster growth rate than did control cells in serum-free medium supplemented with calcium chloride, lithium chloride, sodium selenite, hydrocortisone, and insulin. The cell morphology of c-fos transfected L6J1 myoblasts was not affected compared to control myoblasts. These results suggest that c-fos protein expression in L6J1 myoblasts is activated by serum and that mitogenic stimulation of L6J1 myoblasts is facilitated by the presence of elevated amounts of c-fos protein. PMID- 2105965 TI - Enhanced glycosyltransferase activity during thermotolerance development in mammalian cells. AB - The cellular heat shock response leads to the enhanced synthesis of a family of heat shock proteins and the development of thermotolerance. In CHO cells, however, heat shock also leads to enhanced synthesis of a 50 kD glycoprotein and elevated activity of N-acetylgalactosaminyltransferase (GalNAcT). In this study we showed increased GalNAcT activity during thermotolerance expression in all of five mammalian cell lines included in the study. However, there was no simple correlation between cellular heat sensitivity of unheated control cells and basal levels of GalNAcT activity, measured toward the same exogenous acceptor apomucin. Although GalNAcT was elevated in thermotolerant cells, GalNAcT activity itself did not exhibit thermotolerance in terms of reduced sensitivity to heat inactivation. The increase in GalNAcT activity after heating was similar in exponentially growing and plateau-phase cultures and was inhibited neither by cycloheximide nor actinomycin D. However, the inhibitors by themselves also increased GalNAcT activity in unheated control cells. Chemical inducers of thermotolerance (arsenite and diamide) increased GalNAcT activity, but the increase was modest when compared to that following hyperthermia. In addition to GalNAcT, two other glycosyltransferases with specificity for O-glycans, alpha 1,2 fucosyltransferase and alpha 2,6-sialyltransferase, also showed increased activity after hyperthermia and during thermotolerance development. Together with previously published data, these results support the hypothesis that heat-induced activation of O-glycan-specific glycosyltransferases plays a physiological role in the cellular heat shock response and in thermotolerance development. PMID- 2105966 TI - Fusion of mouse alveolar macrophages induced by 1 alpha,25-dihydroxyvitamin D3 involves extracellular, but not intracellular, calcium. AB - We have reported that the active form of vitamin D3, 1 alpha, 25-dihydroxy vitamin D3 [1 alpha, 25(OH)2D3], directly induces the fusion of mouse alveolar macrophages (Abe et al: Proc. Natl. Acad. Sci. USA 80:5583-5587, 1983). The fusion process can be divided into two phases: the 1 alpha,25(OH)2D3-dependent priming phase (0-18 hr) and the calcium-dependent progression phase (18-72 hr) (Jin et al: J. Cell. Physiol. 137:110-116, 1988). In the present study, we examined the role of calcium in the progression phase of macrophage fusion induced by 1 alpha,25(OH)2D3. Macrophages pretreated with 1 alpha,25(OH)2D3 for 48 hr in a low-calcium (0.13 mM) medium began to fuse quickly 30 min after the culture medium was switched to a normal calcium (1.85 mM) medium. Of various cations tested, calcium was the most effective in inducing fusion, followed by strontium and manganese. Magnesium, potassium, and sodium had no effect. Calcium ionophores such as A23187 and ionomycin did not induce fusion in the low-calcium medium, nor did they potentiate fusion in the media containing higher concentrations of calcium. The intracellular concentration of free Ca2+, measured by a fluorescent method using fura-2 AM, was 116 +/- 1 nM in the macrophages pretreated with 1 alpha,25(OH)2D3 for 48 hr in the low-calcium medium. When calcium chloride was added to the assay system at a final concentration of 1.85 mM, the cytosolic free Ca2+ concentration did not increase appreciably (from 116 to 144 nM). But the macrophages began to fuse quickly when CaCl2 was added. In contrast, adding ionomycin increased cytosolic free Ca2+ from 116 to 440 nM, but no fusion occurred. These results clearly indicate that the extracellular, but not the intracellular, calcium is involved in the progression phase of the fusion of mouse alveolar macrophages primed by 1 alpha,25(OH)2D3. PMID- 2105967 TI - Capillary recruitment of the cerebral cortex during CO2 inhalation: fact or illusion? PMID- 2105968 TI - Health and medicine in Nicaragua. AB - A mass of statistics indicates that the health of the nation as a whole has benefited under the Sandinistas' unified health system. Nevertheless, many physicians and the principal coalition of opposition parties that will oppose the Ortega regime in this month's election advocate replacing it with a three-tiered system aimed at different segments of the population. PMID- 2105969 TI - Humans and animals: increasing contacts, increasing infections. AB - Changes in the zoonotic infections that affect Americans stem primarily from shifting patterns of animal-human interaction, the crossover of species-specific organisms, and the importation or identification of new organisms. Although Lyme disease is not, strictly speaking, zoonotic, it leads off this review by virtue of its epidemic or near-epidemic prevalence in many areas. PMID- 2105970 TI - The human genome--no less! PMID- 2105971 TI - In sickness and in wealth: American hospitals in the twentieth century. PMID- 2105973 TI - Atrial flutter, fibrillation, or artifact? PMID- 2105972 TI - Acute pleurisy in an intravenous drug abuser. PMID- 2105974 TI - The sidewalks of New York. PMID- 2105975 TI - The tumor necrosis factors: cachectin and lymphotoxin. AB - The extensive tissue damage associated with endotoxemia and the phenomenon of tumor necrosis are both triggered by cachectin and lymphotoxin--two leukocyte products with potentially toxic effects on virtually every organ system. Understanding the role of these cytokines in the pathogenesis of inflammation may lead to effective therapy for a wide range of diseases. PMID- 2105976 TI - Rubella-like illness in a pregnant woman. PMID- 2105977 TI - Nodular adrenal hyperplasia--a caveat. PMID- 2105978 TI - Steroids and scleroderma. PMID- 2105979 TI - Mohs micrographic surgery for nonmelanoma skin cancer. PMID- 2105980 TI - Reversing the anemia of renal failure. PMID- 2105981 TI - Silent myocardial ischemia--classification and management. AB - As many as 10% of middle-aged men in the United States may have asymptomatic but active coronary artery disease. Additional patients have silent disease after a myocardial infarction or a combination of silent ischemia and angina. Silent and painful episodes have similar hemodynamic and electrical properties, and antianginal medications appear to have global anti-ischemic effects. PMID- 2105982 TI - The spectrum of alcoholic liver disease. PMID- 2105983 TI - The framework of pathognomonic physical findings. PMID- 2105984 TI - Gender and heart disease. PMID- 2105985 TI - A double-blind study of the efficacy of topical ketorolac tromethamine gel in the treatment of ankle sprain, in comparison to placebo and etofenamate. AB - In a double-blind, placebo-controlled study the efficacy and safety of topical ketorolac tromethamine were assessed in the reduction of inflammation and pain due to ankle sprain. Ketorolac 2% gel was compared with etofenamate and placebo (ketorolac vehicle) in a 15-day study. Patients attended for visits on days 1 (admission), 2, 3, 4, 8, and 15 of the study. Measurements of efficacy were ankle volume, pain measured on visual analogue scales (VAS) and verbal rating of pain. Safety was assessed by volunteered adverse events and vital signs. A total of 37 patients was admitted to the study of whom 13 received ketorolac, 12 placebo, and 12 etofenamate. One patient receiving ketorolac was lost to follow-up on day 15 owing to an unrelated accident. The remaining 36 patients completed the study. Ketorolac was significantly better than placebo in reducing the volume of the injured ankle based on the maximum, the area under the curve, and the day 15 percentage changes in ankle volume. Results for etofenamate were similar to those for ketorolac for all three variables and there were no significant differences between the active treatments. Reductions in VAS pain at rest were more marked in the ketorolac group than either of the other groups at all visits. On day 4 the differences between ketorolac and each of the other groups were statistically significant. Reductions in VAS pain on movement were also greatest for the ketorolac group at all visits. The differences between ketorolac and each of the other groups achieved statistical significance on days 4 and 8, but were marginal in terms of significance on day 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105986 TI - Dermatologic laser surgery. AB - The laser is becoming an increasingly important surgical and medical instrument in the field of dermatology. Developments in the areas of laser technology and application have significantly broadened its clinical use over the past several years. These rapid changes and advances in the use of the laser for cutaneous processes may make it difficult for the physician to maintain a current base of knowledge in this area. Relevant laser systems and their clinical applications are presented and discussed, as are investigational laser systems, which may be of importance for the future. This will allow the dermatologic surgeon the opportunity to update concepts and evaluate the various laser systems and their cutaneous applications. PMID- 2105987 TI - Relatives' involvement in caring for the elderly mentally ill following long-term hospitalization. AB - The involvement of relatives in patient care is frequently associated with 'good nursing practice'. However, according to recent literature it is a practice that is not widely adopted. The intention of this study was to ascertain the extent of relatives' involvement in caring for the elderly mentally ill, from both relatives' and nurses' perspectives. Following analysis of more than 130 questionnaires it was found that nursing staff responded very positively towards greater involvement of relatives wishing to encourage their participation. In comparison relatives felt that their role in patient care was negligible, but despite this did not wish to seek greater involvement. The discussion that follows examines possible reasons for these findings and the implications for future practice. PMID- 2105988 TI - Effect of short-term prostacyclin administration on restenosis after percutaneous transluminal coronary angioplasty. AB - The effect of short-term prostacyclin (PGI2) administration on the incidence of restenosis after coronary angioplasty was studied in a prospective single-blind randomized trial of 286 patients. Of the 270 patients in whom dilation was successful, 134 received prostacyclin and 136 received placebo. Intracoronary prostacyclin was administered before and after dilation and then intravenously for 48 h. The control group received intracoronary placebo infusions before and after dilation. All patients received aspirin and dipyridamole before and after angioplasty, at least until follow-up angiography. Follow-up angiograms were obtained in 93% of patients in whom angioplasty was successful. Restenosis of one or more lesions was present in 34 patients (27%) who were given prostacyclin compared with 40 patients (32%) in the control group (p = NS). Acute vessel closure and ventricular tachyarrhythmias were more common in the control group than in the patients who received prostacyclin (acute vessel closure occurred in 14 [10.3%] of 136 versus 4 [3.0%] of 134, respectively, p less than 0.01; ventricular tachyarrhythmias occurred in 5 [3.4%] of 147 versus 0 of 139 respectively, p less than 0.05). Short-term administration of prostacyclin did not significantly lower the risk of restenosis after coronary angioplasty. PMID- 2105989 TI - Failure of nitroglycerin and diltiazem to reduce platelet-mediated vasoconstriction in dogs with coronary artery stenosis and endothelial injury: further evidence for thromboxane A2 and serotonin as mediators of coronary artery vasoconstriction in vivo. AB - This study was designed to test the efficacy of nitroglycerin and diltiazem in inhibiting in vivo platelet aggregation and reducing platelet-mediated vasoconstriction in a canine model of coronary artery stenosis and endothelial injury. Coronary artery diameter was measured in vivo by means of ultrasonic crystals sutured on the left anterior descending coronary artery (LAD) immediately distal to an external constrictor (LAD1), 1 cm below (LAD2), and on the left circumflex coronary artery. Coronary diameter was continuously measured before, during cyclic flow variations (progressive declines in blood flow followed by sudden restorations of flow due to recurrent intracoronary platelet aggregation), during cyclic flow variations and intravenous infusion of nitroglycerin (5 micrograms/kg per min) or diltiazem (15 micrograms/kg per min), and after cyclic flow variations were abolished by administration of LY53857, a serotonin receptor antagonist (n = 7), or SQ29548, a thromboxane A2 receptor antagonist (n = 7). During control cyclic flow variations, at the nadir of coronary flow (6% to 11% of the nonstenosed values), LAD1 cross-sectional area decreased by 43 +/- 8% and 44 +/- 3% in the two groups of dogs subsequently treated with LY53857 and SQ29548, respectively. Neither nitroglycerin nor diltiazem caused changes in cyclic flow variation frequency or severity. Furthermore, neither drug significantly reduced the vasoconstriction associated with cyclic flow variations, whereas they significantly increased circumflex artery cross-sectional area. In contrast, LY53857 and SQ29548 were very effective in abolishing cyclic flow variations and the coronary vasoconstriction related to them. Five additional dogs received an intracoronary infusion of nitroglycerin (21 +/- 5 micrograms/kg per min) and later diltiazem (15 micrograms/kg per min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2105990 TI - Exercise-induced asthma and the generation of neutrophil chemotactic activity. AB - Heat-stable neutrophil chemotactic activity (HS NCA) has been demonstrated in serum of subjects with asthma after exercise and after allergen inhalation challenge. Heat-labile neutrophil chemotactic activity (HL NCA) has been investigated only after allergen inhalation challenge. In this study, we have measured HS NCA and HL NCA after exercise of 22 adult patients with asthma, 13 of whom had exercise-induced asthma (EIA). In the 13 patients, the effect of pharmacologic pretreatment on the generation of HS NCA and EIA was evaluated in a double-blind study with inhalation of either disodium cromoglycate, terbutaline, or budesonide 15 minutes before exercise. Additionally, the effect of 4 weeks of treatment with budesonide aerosol was evaluated in an open study. A significant increase (p less than 0.01) in HS NCA was found in the patients with EIA with peak activities 15 minutes after exercise. In patients without EIA, the activity of HS NCA was variable. No HL NCA was detectable after exercise. EIA was inhibited by disodium chromoglycate, terbutaline, and 4 weeks of treatment with budesonide. The generation of HS NCA was more or less inhibited by all three drugs with 4 weeks of treatment with budesonide as the most potent regimen. No late-phase asthmatic reactions to exercise were found. It is concluded that only HS NCA is generated after exercise of subjects with asthma and that this production is controlled by antiasthmatic drugs. However, the generation of HS NCA occurs irrespective of EIA. PMID- 2105991 TI - Adenocarcinoma of the ampulla of vater associated with neurofibromatosis. PMID- 2105992 TI - Pancreatic tuberculosis: a frequently fatal but potentially curable disease. AB - A 40-year-old man with prolonged constitutional symptoms and clinical evidence of pancreatitis and biliary tract obstruction underwent exploratory laparotomy. Intraoperative liver and pancreatic biopsies revealed acid-fast bacilli. Mycobacterium tuberculosis subsequently grew from both sputum and urine cultures. The patient responded well to antituberculosis therapy, although 8 months later, he returned with acquired immunodeficiency syndrome (AIDS) and died of large cell lymphoma 1.5 years later. A review of the literature showed that most similar cases of pancreatic tuberculosis were diagnosed only at postmortem examination. A high index of suspicion and attention to special stains are warranted for diagnosis of this frequently fatal, but potentially curable, disease. PMID- 2105993 TI - Human polysaccharide-specific B cells are responsive to pokeweed mitogen and IL 6. AB - The responsiveness of polysaccharide-specific B cells to PWM was examined in vitro. Spleen cells from six patients immunized with Haemophilus influenzae type b-diphtheria toxoid, pneumococcal and meningococcal vaccines were T cell-depleted and separated by Percoll density gradient centrifugation. In each B cell fraction, spontaneous antibody production was demonstrated to capsular polysaccharides as well as diphtheria toxoid. The peak of spontaneous antibody production was demonstrated to be five to seven days after immunization. When T cells and PWM were added, the total Ig secretion increased in all B cell fractions. PWM also enhanced IgG antibody directed to each of three polysaccharide Ag measured. This enhancement was most noticeable for nonresting B cells. The PWM effect was not confined to IgG, as IgM and IgA to Neisseria meningitidis type C were measured and also enhanced. The kinetics of the PWM response demonstrated the most IgG antibody to polysaccharide Ag from spleens immunized five to seven days before splenectomy. When the patients were immunized either 2 days or 4 mo before splenectomy, no spontaneous IgG antibody to polysaccharides was detected although PWM induced small amounts of antibody. Finally, anti-IL-6 antibody blocked PWM-induced total and polysaccharide-specific antibody production. We conclude that human polysaccharide-specific B cells are responsive to PWM and IL-6. We suggest that polysaccharide B cells are not truly "T cell-independent" and may respond to T cell lymphokines and thus are similar to protein-specific B cells. PMID- 2105994 TI - Effects of combinations of transforming growth factor-beta 1 and tumor necrosis factor on induction of differentiation of human myelogenous leukemic cell lines. AB - Effects of transforming growth factor-beta 1 (TGF-beta 1), either alone or in combination with TNF, on the induction of differentiation of human myelogenous leukemic cell lines were examined. TGF-beta 1 alone induced differentiation of a human monocytic leukemia U-937 line into the cells with macrophage characteristics. When combined with TNF, TGF-beta 1 synergistically or additively induced differentiation associated properties. A human myeloblastic leukemia cell line, ML-1, differently responded to TGF-beta 1 in induction of differentiation. FcR activity and phagocytic activity induced by TNF were suppressed by TGF-beta 1. However, nitroblue tetrazolium reducing activity was synergistically induced by combinations of TGF-beta 1 and TNF. Scatchard analysis of TNF receptors indicated that the number of binding sites and dissociation constant of TNF for its receptors on U-937 or ML-1 cells were not changed by treatment with TGF-beta 1. Although IFN-gamma, IL-6, granulocyte CSF, and granulocyte-macrophage CSF induced nitroblue tetrazolium reducing activity of U-937 cells, only IFN-gamma, and TNF induced it synergistically in combination with TGF-beta 1. Synergism between TGF-beta 1 and TNF was also observed in inhibition of growth of U-937 and ML-1 cells. Although TGF-beta 1 induction of differentiation of other monocytoid leukemic THP-1 cells was similar to that of U-937 cells, TGF-beta 1 only slightly induced differentiation of promyelocytic leukemic HL-60 cells, either alone or in combination with TNF. Our observations indicate that TGF-beta 1 strongly modulates differentiation and proliferation of human myelogenous leukemia cells, macrophage precursors. PMID- 2105995 TI - Immunoregulatory functions of paf-acether. IV. Enhancement of IL-1 production by muramyl dipeptide-stimulated monocytes. AB - paf-Acether (paf) is a phospholipid mediator of inflammation released from monocytes along with IL-1. In this study, we have examined the role of paf on IL 1 production by human monocytes. When paf from 1 nM to 5 microM, but not its precursor lyso paf, was added to monocytes in the presence of muramyl dipeptide (MDP) or LPS, a marked increase in IL-1 activity over the value with MDP alone was observed. In contrast, paf alone had minimal activity over the same dose range. Antibodies against rHu IL-1 alpha and rHu IL-1 beta neutralized the increased IL-1 activity. Interestingly, MDP that prompts monocytes to synthesize IL-1, induced the synthesis of paf, as well. Most of the paf produced remained cell-associated and always preceded IL-1 synthesis. When the paf receptor antagonist, L-652,731 was added to monocytes, it prevented the enhancement of IL 1 activity induced by exogenous paf. In contrast, L-652,731 had little effect on MDP-induced IL-1 synthesis in the absence of exogenous paf. This may indicate that there are alternative mechanisms involved in the sequences of events leading to IL-1 production. It is also conceivable that the paf receptor antagonist is not able to compete or inhibit endogenous paf as well as it does for exogenous paf. Nevertheless, exogenous paf in association with a second signal, modulates IL-1 production from human monocytes in a positive manner. This may constitute another means through which paf can modulate inflammatory and immune reactions. PMID- 2105996 TI - Loss of a major idiotype (CRIA) after repopulation of irradiated mice. AB - The normal immune response of A/J mice against arsonate coupled to hemocyanin is characterized by a major recurrent cross-reactive Id, the CRIA. This Id is encoded by a single gene segment combination: VHidcr11-DFL16.1e-JH2 for the H chain and Vkidcr-Jk1 for the L chain. In this report, we show that lethal irradiation of A/J mice followed by reconstitution with autologous or syngeneic lymphoid cells results in loss of major CRIA Id expression in the response to arsonate. Different protocols were performed to repopulate the irradiated mice. First, lethally irradiated A/J mice were reconstituted by the transfer of syngeneic bone marrow cells. Second, A/J mice were lethally irradiated while their hind limbs were partially shielded. Third, lethally irradiated A/J mice received a transfer of syngeneic spleen cells. The three groups of mice produce high titers of antiarsonate antibodies completely devoid of CRIA DH-JH related idiotopes expression. Moreover, a lack of affinity maturation is observed in the secondary antiarsonate response of all irradiated and reconstituted mice. A transfer of syngeneic peritoneal cells or a transfer of primed T cells in irradiated and reconstituted A/J mice do not restore in a significant manner either the recurrent CRIA expression or the affinity maturation of the antiarsonate response. Our data suggest that the choice of this Id is not solely dictated by the Igh locus. PMID- 2105997 TI - Studies on molecular regulation of phagocytosis and activation of the NADPH oxidase in neutrophils. IgG- and C3b-mediated ingestion and associated respiratory burst independent of phospholipid turnover and Ca2+ transients. AB - The role of messengers derived from hydrolysis of phosphoinositides and other phospholipids, of the basal level of [Ca2+]i and of the increase in [Ca2+]i in phagocytosis and respiratory burst was investigated, using normal neutrophils and neutrophils Ca2(+)-depleted by pretreatment with Quin2/AM and EGTA. 1) Phagocytosis and respiratory burst in control neutrophils challenged with yeast opsonized with IgG or C3b/bi were associated with a stimulation of the production of inositol phosphates, diacylglycerol, phosphatidic acid, arachidonic acid, and rise in [Ca2+]i. 2) In Ca2(+)-depleted neutrophils (basal [Ca2+]i 10 to 20 nM) the phagocytosis of yeast-IgG was similar to that in control neutrophils, the respiratory burst was slightly depressed (-30%), while the increase in [Ca2+]i and production of inositol phosphates, diacylglycerol, and phosphatidic and arachidonic acid did not occur. 3) In Ca2(+)-depleted neutrophils the phagocytosis of yeast-C3b/bi was slightly lower than that in control neutrophils, and the respiratory burst, related to the same number of particles ingested, was depressed by about 60%, whereas the increase in [Ca2+]i and production of inositol phosphates, diacylglycerol, phosphatidic acid, and arachidonic acid release did not occur. These findings demonstrate that transmembrane signaling pathways involving the hydrolysis of phosphoinositides by phospholipase C and D and of other phospholipids by phospholipase C and Az, and the rise in [Ca2+]i are not essential processes for triggering the ingestion of yeast particles opsonized with IgG and C3b/bi and the activation of the NADPH oxidase. PMID- 2105998 TI - Comparative studies on lipid and colony-stimulating factor-induced macrophage growth. AB - We previously reported that lipids such as cholesterol esters, triglycerides, and some phospholipids that constitute cell membranes or serum lipoproteins induced growth of mouse peritoneal macrophages in vitro. In this paper, we compared the macrophage growth-stimulating activity of cardiolipin (CL), an active phospholipid with that of CSF-1. Growth kinetics and maximal degree of growth of exudated macrophages induced by CL were similar to those of CSF-1. CL did not stimulate macrophages to release soluble macrophage growth factors. Also, the activity of CL was not blocked as much by anti-CSF-1, suggesting that most of the effect of CL was direct and not mediated by CSF-1 or other protein factors. There was no synergistic effect between CL and CSF-1. CL induced growth of both exudate and resident macrophages, whereas CSF-1 induced very little resident macrophage growth. Furthermore, although the growth-stimulating activities of both substances were inhibited by IFN-gamma and TNF, CL was more resistant to these inhibitory effects. These results suggest that the lipid has some different characters from CSF-1 and may induce the growth of resident macrophages in inflammations or tumors. PMID- 2105999 TI - Eosinophils and immune mechanisms. VI. The synergistic combination of granulocyte macrophage colony-stimulating factor and IL-5 accounts for eosinophil-stimulation promoter activity in Schistosoma mansoni-infected mice. AB - Eosinophil stimulation promoter (ESP) is a lymphokine activity that stimulates eosinophil migration and is produced by mitogen or specific Ag stimulation of spleen cells from mice infected with Schistosoma mansoni. It is also produced by intact, schistosome egg-induced granulomas isolated from the livers of such mice without additional antigenic exposure. The production of ESP activity is decreased during chronic infection in a time course coordinate with granuloma modulation. Characterization of ESP was pursued to determine its relationship to other cytokines and to identify factors that may play a role in granuloma formation and modulation. Chromatographic separations, assays of recombinant cytokines, and cytokine-specific immunodepletions were used in the characterization. ESP+ supernatant fluids contain both granulocyte-macrophage CSF and IL-5. The removal of both granulocyte-macrophage CSF and IL-5 is required to eliminate ESP activity, and together they act synergistically to constitute ESP. PMID- 2106000 TI - Comparison between autoantibodies arising during Trypanosoma cruzi infection in mice and natural autoantibodies. AB - The autoantibodies induced in (C57BL/6 x BALB/c)F1 mice during Trypanosoma cruzi (CL strain) infection were analyzed and compared with natural autoantibodies present in healthy mice. Mice were killed at intervals after infection and their sera were tested by enzyme immunoassay against a panel of self- and non-self-Ag: actin, myoglobin, myosin, tubulin, DNA, and TNP-OVA. The level of IgM and IgG autoantibodies against all Ag started to increase from day 15 until 6 wk after the parasite infection. The high level of all autoantibodies persisted 3 mo postinfection, and 1 yr later, half of the mice still had elevated levels of IgM and IgG autoantibodies, particularly antitubulin IgG antibodies. IgM and IgG were isolated from pools of normal and infected mouse sera and their binding capacity to all Ag was compared. The titers of infected mouse sera were increased and the slopes of both IgM and IgG binding curves of autoantibodies to actin, myosin, and tubulin were greater than those of control mouse sera, indicating higher affinities. The average dissociation constant of the IgG2a autoantibody to mouse tubulin was 5 times lower than that of natural antitubulin IgG2a antibodies. Furthermore, absorption of the IgG from infected mouse sera onto a tubulin immunoadsorbent removed half the reactivity with tubulin and also with myosin, actin and parasite extracts. The eluted antibodies bound the same Ag. When IgG were further analyzed by Western blot on proteolytic fragments of tubulin, we found that antibodies from both groups bound to the same broad spectrum of polypeptide bands. However, additional fragments were recognized by antibodies from infected mice. All these results indicate that the autoantibodies naturally present in mice are significantly affected after infection with T. cruzi, in quantity as well as in specificity and affinity. PMID- 2106001 TI - Increased resolution of lipopolysaccharides and lipooligosaccharides utilizing tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - We utilized the recently described tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (TSDS-PAGE) system to study the lipooligosaccharides (LOS) and lipopolysaccharides (LPS) of gram negative bacteria. TSDS-PAGE resulted in a high degree of resolution of LOS and LPS in the 'mini-gel' format. TSDS-PAGE resulted in the LOS and LPS migrating as a function of their Mr during electrophoresis and allowed estimation of Mr from a protein standard. Several species of LOS were analyzed. The newly described procedure allowed a more rapid and accurate analysis of LOS and the core region of LPS. PMID- 2106002 TI - Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia. AB - Most of human follicular lymphomas possess the t(14;18) chromosome translocation that juxtaposes the IgH gene to the 3' region of bcl-2 in a head-to-tail configuration. Here we show that the rearrangement of the bcl-2 gene occurs in a significant fraction (approximately of 10%) of B cell CLL. In all cases analyzed, breakpoints on chromosome 18 clustered at the 5' flanking region of the bcl-2 gene, and no rearrangements were found at the major or minor breakpoint clustering region (3' region of bcl-2 gene) typical of the t(14;18) chromosome translocation. All of the rearranged bcl-2 genes were juxtaposed with the Ig lambda or K genes in a head-to-head configuration. These results imply that the bcl-2 gene is preferentially linked to the IgL genes in CLL and could function in leukemogenesis. PMID- 2106003 TI - Identifying the RNA polymerases that synthesize specific transcripts of the Autographa californica nuclear polyhedrosis virus. AB - Nuclear run-on assays carried out in the presence and absence of the RNA polymerase II inhibitor, alpha-amanitin, were used to determine the exact timing of the switch from inhibitor-sensitive transcription catalysed by host RNA polymerase II, to inhibitor-resistant transcription catalysed by the baculovirus induced RNA polymerase. These studies revealed that the onset of alpha-amanitin resistant transcription is just after 6 h post-infection, simultaneous with the beginning of the late phase of infection. They also showed that transcripts from the p26 gene in the HindIII Q/P region and the p35 gene in the HindIII K/Q region of the viral genome are synthesized by the host RNA polymerase II both early and late in infection. On the other hand, transcripts of the p10 gene in the HindIII Q/P region and the gamma transcripts in the HindIII K region are synthesized by the alpha-amanitin-resistant, virus-induced RNA polymerase late in infection. PMID- 2106004 TI - Free and antibody-complexed antigen and antibody profile in apparently healthy HIV seropositive individuals and in AIDS patients. AB - The pattern of free and antibody-complexed HIV antigen and the antibody profile were investigated retrospectively in 305 serum samples taken from 22 AIDS patients before and during the development of AIDS and from 40 apparently healthy seropositive individuals. Most AIDS patients were found positive for both free and complexed antigen and had high gp41 antibody titres but low or undetectable p24 antibody. Four different patterns of HIV antigenaemia were observed: 1) positive for both free and complexed antigen; 2) negative for free HIV antigen at first, but always positive for complexed antigen; 3) positive for free antigen without complexed antigen; and 4) negative for both free and complexed antigen. The development of immune complexes preceded the appearance of free antigen and might reflect the ongoing viral replication with antigen excess and binding of anticore antibodies. No correlation was found between the development of AIDS symptoms and either the duration of free antigen positivity or the level of antigenaemia. A different pattern was observed in apparently healthy seropositive individuals: 90% of whom had high antibody titres to p24 and gp41 and were persistently negative for free and complexed HIV antigen. This study demonstrates that testing HIV markers in sequentially collected serum samples from HIV seropositive individuals is a useful and simple tool for early identification of persons at risk of developing AIDS. PMID- 2106005 TI - Serial passage of west-European sporadic non-A non-B hepatitis in rhesus monkeys by inoculation with fecal extracts. AB - An experimental model of sporadic non-A non-B hepatitis involving a Fab nonimmune binding activity in stools was established in the rhesus monkey. The first animal was inoculated intravenously with a stool extract from a French patient who had never left the country and in whom post-transfusion hepatitis was excluded. Four passages were performed, and the infection was transmitted by parenteral as well as the oral routes by inoculation of stools or liver extracts. Infection led in three monkeys to reversible hepatocyte injury manifested by a transitory increase in serum aminotransferases. The other three animals, in which persistently high levels of aminotransferases was observed, were sacrificed on day 60 after inoculation. The incubation period, as evidenced by elevation of aminotransferases was about 3 to 4 weeks. The infectious agent was transitorily present in the stools before aminotransferase elevation. The presence of the infectious agent in the stools was correlated with the nonimmune Fab binding activity. PMID- 2106006 TI - Serological evidence that dry heating of clotting factor concentrates prevents transmission of non-A, non-B hepatitis. AB - A new test for antibodies specific for an agent causing non-A, non-B hepatitis (NANBH) was used to screen 45 children with coagulation disorders who received factor concentrates. It was found that the test results correlated with clinical evidence of NANBH and that heat treatment of concentrates (80 degrees C for 72 hours) appears to have prevented transmission of NANBH. PMID- 2106007 TI - Effect of phospholipase C from Bacillus cereus on the release of membrane-bound choline-O-acetyltransferase from rat hippocampal tissue. AB - Some of the enzyme choline-O-acetyltransferase (ChAT) associated with central cholinergic nerve terminals appears to be non-ionically associated with membranes. In the present study, we tested the possibility that some membrane bound ChAT might be anchored to membranes by a phosphatidylinositol linkage by incubating rat hippocampal tissue with phospholipase C (PLC) from Bacillus cereus. The PLC selectively augmented the release of ChAT; also, the glycosylphosphatidylinositol-PLC inhibitor, zinc, blocked this increase in release. When control and PLC-treated hippocampal tissues were subjected to Triton X-114 phase separation, a procedure that separates amphiphilic from hydrophilic proteins, the detergent-soluble, membrane-bound fraction of tissue ChAT appeared to be the source of the ChAT released by PLC into the incubation medium. Zinc also blocked the temperature-dependent release of ChAT, but not lactic dehydrogenase, from hippocampal tissue. Extracellular membrane-bound ChAT appeared to be the source of the ChAT released by a low exogenous concentration of PLC, as well as that released by a temperature-dependent process during tissue incubation. Phosphatidylinositol-specific PLC from Bacillus thuringiensis released ChAT, but not lactic dehydrogenase, from a crude synaptosomal fraction prepared from rat hippocampal tissue. These results suggest that some of the membrane-bound ChAT in rat hippocampal tissue may be extracellular and anchored to the membrane by phosphatidylinositol, and also that an endogenous factor in hippocampal tissue may function to remove this extracellular ChAT from the membrane. PMID- 2106008 TI - A unique neurofilament from Torpedo electric lobe: sequence, expression, and localization analysis. AB - A set of cDNA clones encoding a protein highly homologous to the mammalian middle size class of neurofilaments (NF-M) was characterized. The amino acid similarity between the Torpedo and rat NF-M approaches 90% in the amino-terminal "rod-like" domain and is significantly lower in the carboxy-terminal tail. The Torpedo protein contains 13 tandem repeats of a unique six amino acid core, containing a Lys-Ser-Lys putative phosphorylation site. Surprisingly, the 3' untranslated region contains stretches of 80-90% nucleic acid homology with the mammalian, but not with the chicken sequences. This homology is greater than much of the coding region, suggesting that the 3' untranslated region of the message has an important functional role, perhaps governing RNA stability or localization. This Torpedo NF-M mRNA is expressed specifically in the electric lobe and was not detected in other tissues, including brain and spinal cord. A polyclonal antibody generated against a fusion protein synthesized in E. coli detects a 150-kDa protein in the electric lobe and organ, as well as a small amount of material in the brain. Cytochemical studies reveal immunoreactivity in electromotor neuron axons and terminals. Specific expression of neurofilament genes in subsets of central neurons may be important in determining the morphology and functional characteristics of specific neuronal subtypes. PMID- 2106009 TI - Arachidonic acid incorporation and redistribution in human neuroblastoma (SK-N BE) cell phospholipids. AB - The incorporation and redistribution of [1-14C]arachidonic acid in SK-N-BE human neuroblastoma cell phospholipids were investigated. By continuous labelling in serum-enriched medium, a rapid radioactivity incorporation into phosphatidylcholine (PtdCho), phosphatidylinositol, and phosphatidylserine was observed; initially, phosphatidylethanolamine (PtdEtn) was poorly labelled, but at later stages it displayed the highest level of arachidonic acid incorporation, in comparison with other phospholipid classes. Labelling of triacylglycerols was also observed. When cells were pulse-labelled with [1-14C]arachidonic acid and then reincubated in label-free medium, a decrease of the radioactivity in triacylglycerols was observed initially, paralleled by an increase of phospholipid labelling; thereafter, arachidonic acid redistribution was consistent with a net decrease of the radioactivity associated with PtdCho acid stable forms (i.e., diacyl plus alkylacyl forms), concomitantly with a net labelling increase of both acid-stable PtdEtn and alkenylacyl-PtdEtn. Data indicate the following: (a) neuroblastoma cells incorporate arachidonic acid into phospholipids through complex kinetics involving transfer of the fatty acid from acid-stable PtdCho to both alkenylacyl-PtdEtn and acid-stable PtdEtn; and (b) triacylglycerols act as storage molecules for arachidonic acid which is subsequently incorporated into phospholipids. The possibility that arachidonic acid transfer to PtdEtn subclasses is driven by distinct mechanisms is discussed. PMID- 2106010 TI - Role of glycine in the N-methyl-D-aspartate-mediated neuronal cytotoxicity. AB - Current evidence indicates that glutamate acting via the N-methyl-D-aspartate (NMDA) receptor/ion channel complex plays a major role in the neuronal degeneration associated with a variety of neurological disorders. In this report the role of glycine in NMDA neurotoxicity was examined. We demonstrate that NMDA mediated neurotoxicity is markedly potentiated by glycine and other amino acids, e.g., D-serine. Putative glycine antagonists HA-966 and 7-chlorokynurenic acid were highly effective in preventing NMDA neurotoxicity, even in the absence of added glycine. The neuroprotective action of HA-966 and 7-chlorokynurenic acid, but not that of NMDA antagonists 3-(2-carboxypiperazine-4-yl)propylphosphonate and MK-801, could be reversed by glycine. These results indicate that glycine, operating through a strychinine-insensitive glycine site, plays a central permissive role in NMDA-mediated neurotoxicity. PMID- 2106011 TI - Transport of lead-203 at the blood-brain barrier during short cerebrovascular perfusion with saline in the rat. AB - Lead transport at the blood-brain barrier has been studied by short (less than 1.5 min) vascular perfusion of one cerebral hemisphere of the rat with a buffered physiological salt solution at pH 7.4 without calcium, magnesium, or bicarbonate and containing 203 Pb-labelled lead chloride. In the absence of complexing agents, 203Pb uptake was rapid, giving a space of 9.7 ml/100 g of wet frontal cortex at 1 min. Lead-203 influx was linear with lead concentration up to 4 microM. Five percent albumin, 200 microM cysteine, or 1 mM EDTA almost abolished 203Pb uptake. Lead-203 entry into brain was uninfluenced by varying the calcium concentration or by magnesium or the calcium blocker methoxyverapamil. Similarly, 1 mM bicarbonate or 50 microM 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid was without effect. Increasing the potassium concentration reduced 203Pb uptake. Vanadate at 2 mM, 2 microM carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (a metabolic uncoupler), or 2 microM stannic chloride all markedly enhanced lead entry into brain, as did a more alkaline pH (7.80). In conclusion, there is a mechanism allowing rapid passive transport of 203Pb at the brain endothelium, perhaps as PbOH+. Lead uptake into brain via this system is probably made less important by active transport of lead back into the capillary lumen by the calcium-ATP-dependent pump. PMID- 2106012 TI - Pain-related somatosensory evoked potentials in cortical reflex myoclonus. AB - To elucidate the sensitivity to pain stimuli in patients with cortical reflex myoclonus, pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation and conventional electrically-stimulated SEPs (electric SEPs) were compared in four patients with cortical reflex myoclonus. The P25 peak of electric SEPs was considerably enhanced but the P320 potential of pain SEPs was of normal amplitude in all patients. After medication, myoclonus was reduced and the amplitude of P25 was decreased, but P320 showed no change. In our previous study of the scalp distribution in normal subjects, a subcortical site, probably the thalamus, was considered to be the generator source of P320. Because most pain stimuli do not reach the cortex, patients with cortical reflex myoclonus are not sensitive to pain stimuli and P320 in pain SEPs is not enhanced. PMID- 2106013 TI - Ramsay Hunt syndrome: to bury or to praise. PMID- 2106014 TI - Postmetamorphic cell death in the nervous and muscular systems of Drosophila melanogaster. AB - Programmed cell death occurs in the nervous and muscular system of newly emerged adult Drosophila melanogaster. Many of the abdominal muscles that were used for eclosion and wing-spreading behavior degenerate by 12 hr after eclosion. Related neurons in the ventral ganglion also die within the first 24 hr. Ligation experiments showed that the muscle breakdown is triggered by a signal from the anterior region, presumably the head, that occurs about 1 hr before adult emergence. The timing of this signal suggests that eclosion hormone may be involved. Although muscle death is triggered prior to ecdysis, it can be delayed, at least temporarily, by forcing the emerging flies to show a prolonged ecdysis behavior. In contrast to the muscles, the death of the neurons is triggered after emergence. The signal for neuronal degeneration is closely correlated with the initiation of wing inflation behavior. Ligation and digging experiments and behavioral manipulations that either blocked or delayed wing expansion behavior had a parallel effect in suppressing or delaying neuronal death. PMID- 2106015 TI - Slow transport rates of cytoskeletal proteins change during regeneration of axotomized retinal neurons in adult rats. AB - To investigate cytoskeletal changes associated with axonal regrowth from damaged nerve cells in the mammalian CNS, we examined the slow transport of axonal proteins during the regeneration of adult rat retinal ganglion cell (RGC) axons. Although normally such RGC axons do not regrow after injury in the CNS, they can extend several centimeters when their nonneuronal environment is changed by replacing the optic nerve (ON) with a grafted segment of peripheral nerve (PN). Proteins transported in axons of RGCs from intact control and PN-grafted animals were labeled by an intraocular injection of 35S-methionine and examined 4-60 days later by SDS PAGE. During RGC regeneration into PN grafts, the transport rate of tubulin and neurofilament increased twofold, whereas that of actin decreased to nearly one third of its normal rate. Thus, in these regenerating RGC axons, all three major cytoskeletal proteins were largely transported within a single rate component rather than in the two separate components (SCa and SCb) normally observed in the intact ON. Furthermore, the 200 kDa neurofilament protein (NF-H) was persistently detected in Western blots during periods of active regeneration, a finding that contrasts with the late appearance of the NF-H during the developmental growth of retinal axons. The changes in slow transport observed during RGC regeneration in adult rats may reflect growth-associated responses of mature CNS neurons during periods of active axonal extension. PMID- 2106016 TI - Effect of hyperosmotic blood-brain barrier disruption on transcapillary transport in canine brain tumors. AB - Whether hyperosmotic blood-brain barrier (BBB) disruption is a technique that can be used to increase permeability of brain-tumor capillaries and thereby transiently increase drug delivery to the brain tumor is controversial. Nine virally induced brain tumors were studied in seven dogs, before and after hyperosmotic BBB disruption with 1.4 osmolar mannitol. Each dog was studied with computerized tomography (CT) after administration of the water-soluble tracer meglumine iothalamate. Each study lasted 30 minutes. A baseline CT scan and 35 to 40 additional CT scans were obtained to provide a time-related measurement of the amount of meglumine iothalamate in tissue (Am(t], and 30 plasma samples were collected to provide the time-related measurement of meglumine iothalamate in plasma (Cp(t]. The data were analyzed by three different methods: 1) a two compartment model and nonlinear curve fitting were used to calculate K1 (blood-to tissue or influx constant), k2 (tissue-to-blood or efflux constant), and Vp (plasma vascular space); 2) K1 values were calculated with a two-compartment model, assuming no efflux, at the time point for each CT scan; and 3) a "tissue advantage ratio" was calculated that expressed the ratio of tissue uptake of meglumine iothalamate at each time point, comparing values before and after BBB disruption. Regardless of which method of data analysis was used, there was a marked and significant increase in transcapillary transport of meglumine iothalamate to tumor-free brain regions, while there was only a small, transient, and insignificant increase to the brain tumors. Although there were often marked increases in delivery to cortex in the same hemisphere as the tumors, there was no significant increase to brain immediately surrounding the tumors, perhaps due to altered circulatory dynamics in this region. These data raise serious questions as to the wisdom of using this technique to increase drug delivery to brain tumors in patients and strongly support the continued study of this technique in experimental brain tumors before it is used in patients. PMID- 2106017 TI - Dietary supplementation with oils rich in (n-3) and (n-6) fatty acids influences in vivo levels of epidermal lipoxygenase products in guinea pigs. AB - Certain dietary oils may have therapeutic potential in the treatment of inflammatory skin disorders. Presumably, the fatty acid constituents of these dietary oils exert their effects by altering the levels of cutaneous eicosanoids. Prompted by this possibility, we investigated whether supplementation of guinea pig diets with fish oil [rich in 20:5(n-3)] or borage oil [rich in 18:3(n-6)] could significantly alter epidermal levels of eicosanoids compared with control animals supplemented with olive oil. After feeding periods of 4, 8 or 12 wk, the epidermis from the animals was analyzed for: 1) fatty acid composition of individual epidermal phospholipids, 2) levels of lipoxygenase products, and 3) levels of cyclooxygenase products (prostaglandins). Our results demonstrated that the animals supplemented with dietary fish oil had elevated levels of 20:5(n-3) in epidermal phospholipids and elevated epidermal levels of 15 hydroxyeicosapentaenoic acid (15-HEPE) [the 15-lipoxygenase product of 20:5(n-3)] compared with guinea pigs fed olive oil or borage oil. Similarly, the animals supplemented with dietary borage oil had elevated levels of 20:3(n-6) [the epidermal elongase product of 18:3(n-6)] in epidermal phospholipids and elevated epidermal levels of 15-hydroxyeicosatrienoic acid [15-HETrE, the epidermal 15 lipoxygenase product of 20:3(n-6)] compared with guinea pigs fed olive oil or fish body oil. There were no significant changes in epidermal levels of prostaglandins. Both 15-HEPE and 15-HETrE have been identified as possible anti inflammatory metabolites, and their elevated presence in the epidermis of animals fed oils rich in 20:5(n-3) or 18:3(n-6) may provide a mechanism for the beneficial effects of these oils on inflammatory conditions. PMID- 2106018 TI - The effectiveness of flumazenil in reversing the sedation and amnesia produced by intravenous midazolam. AB - In this double-blind study 31 outpatients undergoing third molar extraction were randomly assigned to one of two groups. All patients were sedated with intravenous midazolam (IV) by titration method. The flumazenil group (n = 20) received an average of 0.8 +/- 0.17 mg of flumazenil IV. The placebo patients (n = 11) each received 10 mL of normal saline. By both observer and patient alertness ratings, patients receiving flumazenil appeared significantly more alert than placebo patients at 5, 15, 30, and 60 minutes following reversal. After reversal the flumazenil group had significantly higher scores than the placebo group at all intervals through 60 minutes. All the patients receiving flumazenil were able to walk without assistance at 5 minutes, compared with only one patient in the placebo group, and more patients in the flumazenil group recognized the picture card shown to them at 5, 15, 30, and 60 minutes postreversal. Flumazenil is effective in terminating the amnestic properties of midazolam, but this appears to occur to a lesser extent than the reversal of its sedative properties. PMID- 2106019 TI - In situ cross-linking of cartilage proteoglycans. AB - Although the in vitro interactions between purified cartilage matrix components have been studied extensively, little is known about these interactions in situ. In this study, cartilage was treated with a cross-linking reagent with a span of 1.2 nm between its reactive terminal groups in order to preserve the native relationships between closely associated matrix components throughout extraction, purification, and preparation for electron microscopy. After in situ cross linking, electron microscopy and gel chromatography revealed that about one-half of the guanidine hydrochloride extractable proteoglycans were polymeric, usually with two to five proteoglycan subunits in each polymer. Cross-linking consistently involved the thin segments of the proteoglycan subunits. Some of the proteoglycan polymers were capable of binding hyaluronic acid and were parts of aggregates under associative conditions. SDS-polyacrylamide gel electrophoresis revealed that link proteins were present within the polymers, and studies in which purified proteoglycans were cross-linked in vitro confirmed that the link proteins increased the proportion of polymeric proteoglycans. These findings suggest that individual proteoglycans within cartilage have intimate associations with other proteoglycans that are mediated by link proteins. PMID- 2106020 TI - Apolipoprotein A-I:B ratio and B screening: a preliminary study of 10- and 11 year-old children. AB - The apolipoprotein (apo) A-I:B ratio and the apo B concentration were determined by radial immunodiffusion in dried blood spot samples from 1,767 10- and 11-year old children. Children with either apo A-I:B ratios below the first percentile or apo B levels above the 99th were recalled and plasma lipid and apolipoprotein profiles were determined for both children and parents. Of 17 children (one family was lost to follow-up) recalled due to abnormal apo A-I:B ratios, apo B levels were above the 95th percentile in 13 children, and of 18 children with abnormal apo B screening levels (three of them also had abnormal apo A-I:B ratios), the plasma apo B level was elevated in 13 children. The 23 children with abnormal blood lipid and/or apolipoprotein concentrations were divided into two main groups: (a) children with type IIa hyperlipoproteinemia and (b) children with hyperapo B lipoproteinemia (hyperapo B) and normal blood lipid levels. Twelve children had the type IIa pattern. Five children likely had familial hypercholesterolemia (FH), the other seven children may have hypercholesterolemia due to obesity or environmental factors. Eleven children had the hyperapo B abnormality. In four children, the elevated apo B level probably was an indication of the occurrence of familial combined hypercholesterolemia (FCH) in the family. Of the remaining seven hyperapo B children, three children also had a parent with hyperapo B and a fourth family suffered from obesity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106021 TI - [51Cr]EDTA intestinal permeability in children with cow's milk intolerance. AB - Making use of [51Cr]EDTA as a permeability marker, we measured intestinal permeability in a group of 20 children with proven cow's milk intolerance (CMI), a group of 17 children with similar complaints where CMI was excluded (sick controls), and a group of 12 control children. [51Cr]EDTA test results (mean +/- SD) were 6.85 +/- 3.64%, 3.42 +/- 0.94%, and 2.61 +/- 0.67% in the group with CMI, the sick control, and the control group, respectively. When compared to both control groups, patients with cow's milk intolerance (CMI) showed a significantly increased small bowel permeability. We conclude that the [51Cr]EDTA test can be helpful for the diagnosis of cow's milk intolerance. PMID- 2106022 TI - Exacerbation of human immunodeficiency virus infection in promonocytic cells by bacterial immunomodulators. AB - Common bacterial infections are increasingly being diagnosed in HIV-infected individuals. Cells of the monocyte-macrophage lineage kill invading bacterial pathogens and subsequently release immunoadjuvant components from the degraded cell walls. Since monocytes can be infected with HIV, effects of bacterial immunomodulators on infected promonocytic U937 cells were investigated. Synthetic muramyl peptide, mycobacterial trehalose dimycolate, and detoxified endotoxin exhibited an initial reduction followed by a rapid increase in HIV p24 antigen production. The upregulation of virus expression was correlated with enhanced interleukin-1 beta levels and a decrease in TNF-alpha production. PMID- 2106023 TI - Isolation and characterization of cell clones persistently producing teardrop shaped particles of human immunodeficiency virus type 1. AB - Several cell clones producing teardrop-shaped human immunodeficiency virus type 1 (HIV-1) particles were isolated from MT-4 cells that survived HIV-1 infection after extensive cell lysis. Most of the teardrop-shaped particles contained an electron-dense core structure, and the particles could replicate in MT-4 cells. No significant structural difference in the HIV-1 proteins was observed between these cell clones and the MOLT-4 cells producing intact HIV-1 particles, although their envelope structure is morphologically abnormal. PMID- 2106024 TI - Laboratory evidence of active HIV-1 infection in Canadians with hemophilia associated with administration of heat-treated factor VIII. AB - Heat-treated factor VIII has been implicated in the transmission of HIV to hemophiliacs. Previously, evidence has been limited to documenting cases of seroconversion following administration of heat-treated factor VIII. Here, we present evidence of active HIV infection, i.e., infected and not merely sensitized following factor VIII injections. Six Canadians with hemophilia had seroconverted during a longitudinal study of their HIV immune status. Two of the three patients tested by this method demonstrated HIV gag-specific sequences upon amplification by polymerase chain reaction. In addition, HIV-1 virus was isolated from peripheral blood lymphocytes of one of these two persons as shown by reverse transcriptase activity of culture supernatants as well as neutralizable p24 antigen. This, we believe, is the first evidence of active HIV infection following administration of 60 degrees C, 30 h heat-treated factor VIII. PMID- 2106025 TI - Peroneal sheath reconstruction in the growing child. AB - The authors recommend the procedure described above specifically for children with congenital or acquired subluxation or dislocation of the peroneal tendons, but they advise against using this procedure alone when calcaneovalgus deformity is present and anterior dislocation of the peroneal tendons occurs as a result of spasticity. It may, however, have a place as part of a combined procedure to correct the spastic deformity. Reconstruction of the superior peroneal retinaculum is accomplished with a strong ligamentous structure, appropriately oriented and directed, without loss of lateral ankle stability. The authors believe that the complication of partial or complete fibular physeal arrest can be avoided, and that redislocation of the peroneal tendons as the child grows out of the repair can be eliminated. Therefore, this procedure is suggested as the procedure of choice for a growing child with anterior luxation or dislocation of the peroneal tendons and an intact calcaneofibular ligament. Properly performed, it will enable these children to return to the vigorous physical activity they desire. PMID- 2106026 TI - The effect of immersion disinfection of elastomeric impressions on the surface detail reproduction of improved gypsum casts. AB - This investigation examined improved gypsum casts for surface roughness and line detail reproduction after the immersion disinfection of elastomeric impression materials in an acid glutaraldehyde, an alkaline glutaraldehyde, and a phenol. Impressions were made of a surface roughness standard (Ra = 3.08 microns) that was custom made to include engraved grooves following American Dental Association specification No. 19. Mean surface roughness (Ra) values for all casts of all combinations of disinfectant treatments, impression materials, and improved gypsum stones were obtained with a surface analyzer. Untreated impressions served as controls. Data examined by an analysis of variance indicated that the addition silicone and polyether impression materials provided a surface roughness similar to the precision displacement specimen standard. The acid glutaraldehyde disinfectant demonstrated enhanced line-detail reproduction compared with the standard. Addition silicone and polyether impression materials combined with the acid glutaraldehyde provided the model system closest to the mean surface roughness of the reference standard. These combinations revealed differences in the surface roughness reproduction among the represented improved dental stones. PMID- 2106027 TI - Morphology and development of mirror-image doublets of Stylonychia mytilus. AB - This paper describes the cortical anatomy and development of mirror-image doublets of Stylonychia mytilus, analyzed using the protargol technique. The reversed, or "left-handed" (LH) component of these doublets is a mirror image of the normal or "right handed" (RH) component with regard to the arrangement of cortical structures. The mirror-image patterning is imperfect, however, as the individual ciliary structures of the LH component all are of normal internal asymmetry, and the orientation of membranelles is inverted. Certain structures that would be expected to form near the line of symmetry are absent. During cell division and cortical reorganization, ciliary primordia arise and become arranged in a mirror-image pattern that is more perfect than that exhibited by the mature structures. Deviations from a mirror-image pattern appear at late stages when organelle sets differentiate within ciliary primordia: for example, the membranelle set differentiates within the oral primordium of the LH component in a sequence that is an inversion rather than a mirror image of the corresponding sequence of the RH component. This mixed control of oral development by different cortical "informational systems" accounts for some of the characteristic abnormalities of the mature oral structures of the LH component. PMID- 2106028 TI - Morphology and development of left-handed singlets derived from mirror-image doublets of Stylonychia mytilus. AB - Mirror-image doublets of Stylonychia mytilus include 2 sets of cortical structures, one with the normal "right-handed" (RH) arrangement, the other with a reversed "left-handed" (LH) arrangement. These sets, however, are incomplete, with certain structures, most notably cirri of the right marginal type, missing near the line of symmetry. When a mirror-image doublet is bisected longitudinally to separate the RH and LH components physically, each fragment undergoes a regeneration process that restores a complete set of cortical structures, including the previously missing cirri of the right marginal type. In the resulting LH cell, all ciliary structures are present in an arrangement that is globally reversed in relation to that found in RH cells; in particular, marginal cirri of the left-marginal type are formed at the cell's right margin, and marginal cirri of the right-marginal type are produced at the cell's left margin. Whereas the regenerated RH fragment always divides and initiates a clone of normal singlets, the LH fragment, though structurally nearly complete, in all cases eventually dies without dividing. The cause of death is starvation due to the formation of an abnormal oral apparatus. In the Discussion, we consider the nature and consequences of a reversal of global positional information. PMID- 2106029 TI - Sextuplet pregnancy after human menopausal gonadotropin superovulation and intrauterine insemination. A case report. AB - Sextuplet pregnancy occurred after human menopausal gonadotropin ovulation induction, intrauterine insemination and human chorionic gonadotropin support in the luteal phase. The patient's peak serum estradiol concentration was 861 pg/mL, and ultrasound monitoring demonstrated only one follicle greater than 11 mm in diameter. The possibility of high-order multiple birth exists despite intensive monitoring efforts for this therapy. PMID- 2106030 TI - Effect of ultrasound monitoring of follicular growth on the conception rate. A clinical study. AB - Periovulatory ultrasonography (POUS) was performed on 59 anovulatory women over 523 treatment cycles. Follicular development was stimulated with either clomiphene citrate (CC) or human menopausal gonadotropin (hMG). Thirty-one pregnancies were induced; 23 went to term. Three factors were considered in evaluating the incidence of conception: the patient's age, drug use and the presence or absence of POUS. There was no evidence that the pregnancy rate after POUS differed from that without it (estimated conception rate ratio = 1.2:1, P = .76). Similarly, conceptus viability was not demonstrably different whether POUS was used or not (P = 1.00). However, the data show a strong advantage of hMG over CC in achieving conception (estimated conception rate ratio = 5.85, P less than .0001) and no disadvantage in conceptus viability (P = 1.00). The data also suggest that in women less than 30 years of age with polycystic ovaries, ovulation induction is easier to achieve and the conception rate higher than in older women. There was no evidence that POUS decreased the conception rate or increased fetal wastage. PMID- 2106031 TI - When is treatment for cancer economically justified? Discussion paper. PMID- 2106032 TI - Seizure induction by alcohol in patients with epilepsy experience in two hospital clinics. AB - We surveyed 70 epileptic patients attending a general neurology clinic and 64 patients attending an epilepsy clinic to determine the incidence of alcohol related seizures. Seven (10%) of the neurology clinic patients and 9 (15%) of the epilepsy clinic patients reported exacerbation of their seizures with alcohol. In the first group, two had been heavy drinkers when under-age, two had features of alcohol dependence, and three had experienced resolution of seizures following cessation of their drinking. In the second group, five drank 4 units/day or more, and one drank more heavily. The importance of alcohol in the causation of these patients' seizures had not previously been appreciated. The relationship of alcoholism to epilepsy has been recognized for many years, but the role of alcohol in the exacerbation of primary epilepsy, and in triggering seizures in epileptic patients is often not recognized. Control of alcohol ingestion is an important factor in the management of epilepsy. PMID- 2106033 TI - Ecology of Pseudomonas aeruginosa in patients with cystic fibrosis. AB - The occurrence of various Pseudomonas aeruginosa strains in the sputum of 15 patients with cystic fibrosis (CF) was monitored over periods ranging from 2 to 60 months. Isolates of P. aeruginosa were typed by four different techniques, namely serotyping, active and passive pyocin typing, and phage typing. The maximum number of different serotypes found in the patients was three (one serotype in nine patients; two serotypes in five patients; three serotypes in one patient). Pyocin and phage typing showed no marked differences between strains of the same serotype in individual patients. Exacerbations of chronic respiratory infection were not associated with changes in the sputum flora, the composition of P. aeruginosa strains in which remains constant over long periods in patients with CF. PMID- 2106034 TI - A pyrolysis-mass spectrometry study of Corynebacterium spp. AB - Clinical (66) and collection (38) strains of Corynebacterium spp., including C. jeikeium and CDC group D2, and of Listeria monocytogenes were examined. Conventional characters used in species identification were assessed by a microbiochemical method, and pyrolysis-mass spectrometry (Py-MS) was performed with a Horizon Instruments PYMS 200X. Classification based on Py-MS data yielded clusters that corresponded with species identification and classification groups from conventional data. One small group of clinical strains, homogeneous in conventional tests and Py-MS, comprised isolates from sputum samples from patients undergoing ventilation; they were similar to collection strains of C. renale and C. striatum; the latter species has been implicated in chest infection. Another group, similar to C. minutissimum in both systems, comprised clinical strains isolated from urogenital specimens. L. monocytogenes strains were clearly distinct from Corynebacterium spp. Groups comprising CDC D2 strains and C. jeikeium were resolved, and were similar to other Corynebacterium spp. Two collection strains of C. xerosis were distinct in conventional tests and Py-MS. PMID- 2106035 TI - Prolonged survival by tumor-bearing rats treated with acivicin and total parenteral nutrition. PMID- 2106036 TI - Arterial blood gas and expiratory pressure monitoring in infants with pneumothorax: prognostic predictability. AB - Infants presenting with pneumothorax within the first 24 hours of life were studied in an attempt to produce a reliable index of the severity of the disease. Of these 54 patients, 46 infants required intubation and ventilator support; 18 (39%) survived and 28 (61%) died. Overall mortality in this series was 52%. We have been able to define clearly the two groups (survivors and nonsurvivors) based on their response to ventilatory parameters. The nonsurvivor group displayed CO2 retention associated with pneumopericardium and pulmonary interstitial emphysema. This group was unresponsive to high fraction of inspired oxygen and high positive end expiratory pressure. The survivor group responded well to a fraction of inspired oxygen of less than 70% and a positive end expiratory pressure of 6 cm or less. Arterial CO2, pneumopericardium, pulmonary interstitial emphysema, pneumomediastinum, and birthweight are useful in predicting the severity of the respiratory distress in these infants and in evaluating the nonsurvivors from the survivors. PMID- 2106037 TI - Nutritional impact on the energy cost of fat fuel mobilization in polytrauma victims. AB - In the "flow" phase of severe injury, mobilization of body fat and protein sources are accelerated to meet increased demands. Fat mobilization usually exceeds the need for oxidative substrates and the leftover fatty acids are re esterified, resulting in a "futile" TG/FFA cycle. This contributes to increased energy expenditure and provision of nutrients may alter the activity of this cycle. We measured in nine adult (age 40 +/- 7 years, weight, 80 +/- 4 kg) severely traumatized (ISS 32 +/- 4) patients, the resting energy expenditure (REE) and net fat oxidation rate (NFO) by indirect calorimetry and whole body lipolysis rate (WBLR) by a two-stage, primed-constant infusion of glycerol. Fasting postinjury kinetic studies were performed within 48-96 hours after admission when the patients were receiving saline without calories or nitrogen. Glucose-based nutritional therapy was then started and continued for 5 to 7 days. The kinetic measurements were repeated after the nutritive solutions were replaced by normal saline for 12 to 15 hours to achieve a postabsorptive state. Trauma elicits an accelerated rate of fat mobilization with increased TG/FFA cycle activity. Adequate nutritional support for 5 to 7 days tends to reduce but cannot normalize the lipid metabolism. In acute trauma 47 +/- 7% of the mobilized fat was recycled to triglyceride and this is increased to 54 +/- 9% after providing nutrition. The energy cost of this cycling was 38 kcal/day, which is five times that seen in normals and corresponds to 1.34% REE. PMID- 2106038 TI - A parasitological and malacological survey of schistosomiasis mansoni in the Beles Valley, northwestern Ethiopia. AB - A survey of schistosomiasis mansoni infection was conducted in an area of northwestern Ethiopia which has been targeted for an irrigation project. The proximity of settlements to water-bodies infested with Biomphalaria pfeifferi, and used extensively for bathing and domestic purposes, indicated that the potential for transmission is high. Snails shedding S. mansoni cercariae were found in two localities. Stool specimens from a total of 7517 persons were examined, including specimens from 4915 children age 7-14 years in 29 localities, as well as from the total population of four of the more heavily infected localities. The 10-14 year age group had the highest transmission potential, in terms of prevalence (overall 25%), intensity of infection, and absolute numbers of infected individuals, suggesting that screening and chemotherapy would be most cost-effective in that age group. PMID- 2106039 TI - Regulation of expression of a baculovirus ecdysteroid UDPglucosyltransferase gene. AB - The Autographa californica nuclear polyhedrosis virus egt gene encodes an ecdysteroid UDPglucosyltransferase which catalyzes the transfer of glucose from UDPglucose to ecdysteroid insect molting hormones. Expression of this gene allows the virus to block molting and pupation of infected insect larvae. In this study, we present the nucleotide sequence of the A. californica nuclear polyhedrosis virus egt gene and characterize egt gene expression at the transcriptional and translational levels. egt was transcribed as two 5'-coterminal mRNAs early in infection. Transferase activity was detected in infected cells and in the extracellular fluid by 3 h after infection. The majority of the activity accumulated in the extracellular fluid. We show that the egt gene product is a 60 kilodalton protein which is secreted from the infected cell. The egt gene is located in a region of the A. californica nuclear polyhedrosis virus genome which exhibited hypervariability in serially passaged virus stocks. Nucleotide sequence analysis revealed that the most common deletion occurring in these serially passaged virus isolates is located in the egt gene. PMID- 2106040 TI - Expanding the role of the ureteroscope. AB - Although the rigid ureteroscope was designed exclusively for the diagnosis and treatment of pathological conditions of the ureter, its smaller diameter and extended length allow for its increased use in endoscopic procedures that cannot be performed successfully with a cystoscope. The indications can be divided into 3 categories: 1) difficult ureteral catheterizations, 2) augmented bladders and diverticula, and 3) narrow, strictured urethras and bladder necks. Several cases from each category are presented to illustrate the expanded role of the rigid ureteroscope in daily urological practice. PMID- 2106041 TI - Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. AB - We report the second interim analysis of data from a randomized prospective trial comparing the prophylactic effect of 15 courses of 50 mg. doxorubicin, 50 mg. thiotepa or 150 mg. bacillus Calmette-Guerin instilled intravesically against recurrences and progression of superficial transitional cell bladder cancer. Of 202 enrolled patients 176 currently are evaluable with a mean follow-up of 3 years (range 3 to 97 months). The number of patients with recurrences was significantly lower in the bacillus Calmette-Guerin arm (9 of 67) compared to the doxorubicin (23 of 53, p equals 0.002) and thiotepa (20 of 56, p equals 0.003) arms. The over-all recurrence index per 100 patient-months also was lower for the bacillus Calmette-Guerin versus the thiotepa and doxorubicin groups (0.53 versus 1.55 and 1.7, respectively). Bacillus Calmette-Guerin also was superior in preventing recurrences and progression of high risk tumors, that is stage T1, grade 3 or multiple growths, associated or not with carcinoma in situ. In the stage T1 category 19 of 32 (60%) tumors recurred under treatment with doxorubicin, 11 of 33 (33%) with thiotepa and 6 of 49 (12%) with bacillus Calmette-Guerin. Toxicity to intravesical bacillus Calmette-Guerin was higher compared to the other drugs but it was not limiting: bladder irritability and malaise occurred in 42% of the patients, granulomatous cystitis in 16.4% and bladder contraction in 1.4% (1 of 64). The latter complication occurred in a patient whose stage T1m grade 2 tumors had recurred 3 times, who underwent 3 transurethral bladder resections within 15 months and who had received thiotepa for 4 months after having been removed from the study 11 months after entry. Three patients in the doxorubicin group (5.6%) underwent radical cystectomy for local urothelial progression. One patient (1.8%) in the same group died of distant progression. Our preliminary results suggest that at the dose, periodicity and duration used in the study bacillus Calmette-Guerin is significantly superior to the chemotherapeutic agents doxorubicin and thiotepa for the prophylaxis of recurrence and retardation of progression in superficial transitional cell bladder tumors. PMID- 2106042 TI - Re: Topical nitroglycerin: a potential treatment for impotence. PMID- 2106043 TI - The glycosaminoglycans of the gubernaculum during testicular descent in the fetus. AB - Tissues were obtained from 387 male pig fetuses ranging from 60 to 120 days of gestation. The relative wet mass and water content of the gubernaculum increased during and decreased after the period of testicular descent. The extracellular glycosaminoglycans (GAG) were assayed to determine whether these polyanionic macromolecules are responsible for the increased water content of the gubernaculum. The total GAG/wet tissue mass in the gubernaculum decreased during and increased after descent, while the total GAG/dry mass decreased during and after descent, indicating an accumulation of water during descent, with a loss of water and an increase in less hydrated tissue components after descent. The major GAG fraction in the gubernaculum was dermatan sulfate, but the percentage hyaluronate in the gubernaculum was two times higher than in striated muscle or umbilical cord, indicating that this GAG fraction may be responsible for the increased water content of the gubernaculum, which probably serves to dilate the inguinal canal and scrotum, thus facilitating descent. PMID- 2106044 TI - Serologic survey of selected zoonotic disease agents in black-tailed jack rabbits from western Texas. AB - A serologic survey for the agents of Rocky Mountain spotted fever (RMSF) (Rickettsia rickettsii), Borrelia spp. including the causative agent for Lyme disease (Borrelia burgdorferi), and plague (Yersinia pestis) was conducted on blood samples collected from 30 and 46 black-tailed jack rabbits (Lepus californicus) from an urban environment in Lubbock, Texas (USA) during winter 1987 and the following spring 1988, respectively. Antibody titers to the agents of RMSF and borreliosis were detected in sera of 28 and 1% of the jack rabbits, respectively. Neither organisms (rickettsiae and/or spirochetes) nor their associated antigens were detected in any of the tissue or whole blood samples; plague antibodies were not detected in the 76 jack rabbits sampled. Four of 18 ticks (Dermacentor parumapertus) removed from 12 jack rabbits were positive for RMSF using the fluorescent antibody test. The black-tailed jack rabbit is a common wildlife species living in close proximity to higher density human populations in many areas of the southwestern United States. Our results indicate the potential importance of urban populations of this mammal as reservoirs for at least one important zoonotic disease, RMSF, in western Texas. PMID- 2106045 TI - Home care in the 1990s. Council on Scientific Affairs. AB - Home care is a rapidly growing field that is beginning to attract greater physician interest and participation. Cost-containment pressures have led to reduced institutionalization in hospitals and nursing homes and to more patients, both acutely and chronically ill, being cared for in their own homes. Undergraduate and graduate medical education programs are developing home care curricula, and academic medicine is beginning to develop a research agenda, particularly in the area of clinical outcome measurements. Medical care in the home is highly diversified and innovative. The areas of preventive, diagnostic, therapeutic, rehabilitative, and long-term maintenance care are all well represented as physicians develop new practice patterns in home care. PMID- 2106046 TI - [Infection in acute pancreatitis]. PMID- 2106047 TI - The analysis of lymphocyte surface receptors recognized by wheat germ agglutinin for negative regulation of immune responses in cancer patients. AB - The population of peripheral blood lymphocytes expressing surface receptors for a lectin, wheat germ agglutinin (WGA), which has been shown to recognize the same receptors as the soluble immune suppressor factor (SISF) elaborated from suppressor cells on the lymphocyte surface, was analyzed by using fluorescein isothiocyanate-conjugated WGA on flow cytometry in cancer patients. It was found that the populations of WGA+ lymphocytes in cancer patients were significantly higher than those in either normal volunteers or patients with benign disease and increased with progress of the tumor. The populations decreased after treatment in patients who underwent curative resection of the tumor and in responders of immunochemotherapy but not in those who received non-curative surgery or in non responders. It was suggested that the increase of receptors for SISF on the lymphocyte surface might play an important role in the negative regulation of immune responses in cancer patients and that WGA might be a useful parameter for immunosuppression. PMID- 2106048 TI - Changes in the hormone receptors of human breast carcinoma xenografts in nude mice by treatment with cytotoxic agents. AB - We examined the effect of chemotherapeutic agents on the estrogen receptors (ER) of breast carcinomas in vivo using human breast carcinoma strains (Br-10, T-61) serially transplanted into nude mice. When the tumor size reached approximately 1 X 1 X 1 cm, mitomycin C (MMC) at doses of 1, 2 and 4.5 mg/kg and cyclophosphamide (CPA) at a dose of 120 mg/kg, were administered once intraperitoneally, and the ERs of the tumors were measured sequentially by the dextran-coated charcoal method. Four days after the MMC administration at above doses, the binding sites of ER in Br-10 were not reduced and binding affinity was not affected. When the changes in ER content with time after the treatment with 4.5 mg/kg MMC and 120 mg/kg CPA were investigated, the ER content was found to be stable until 4 days after the treatment with both drugs, although the growth of T-61 had been significantly inhibited by the drugs. From these findings, it seems reasonable to initiate chemotherapy before endocrine therapy, since the chemotherapeutic agents did not reduce the ER content of the breast cancer strains. PMID- 2106049 TI - [Changes in the nursing profession 1939-1989. From vocation to profession--from serving to service]. PMID- 2106050 TI - [Hospital financing]. PMID- 2106051 TI - [Alternatives in nursing. 4. The Essen nursing symposium. Interview by Eva Maria Krampe]. PMID- 2106053 TI - [Nursing oriented electronic data processing. Expectations and requirements--from the viewpoint of the nursing service]. PMID- 2106052 TI - [Stress in the old age home]. PMID- 2106054 TI - Isolation and identification of strains of Bacteroides fragilis group from the digestive tract of Callithrix penicillata marmosets. AB - Thirty-five strains of the Bacteroides fragilis group were isolated from oral and intestinal samples from 5 wild caught, captive Callithrix penicillata. Nine oral strains of Bacteroides fragilis (7) and Bacteroides distasonis (2), and 26 intestinal strains of Bacteroides fragilis (14) and Bacteroides distasonis (12) were identified. PMID- 2106055 TI - 3,4,3',4'-Tetrachlorobiphenyl distribution and induced effects in the rat adrenal gland. Localization in the zona fasciculata. AB - The distribution of radiolabeled 3,4,3',4'-tetrachlorobiphenyl (TCB) and TCB induced effects on serum and adrenal gland retinoid content, and adrenal gland morphology was studied by liquid scintillation counting, high performance liquid chromatography, light microscopic autoradiography, and transmission electron microscopy. Adult, female WAG/Rij rats received a single intraperitoneal injection of either vehicle (corn oil), 15 mg TCB/kg, or 200 mg TCB/kg body weight and were sacrificed (N = 3 per group) at 1, 3, 7, and 14 days after treatment. One rat of the high dose group that was sacrificed at each sampling time had received radiolabeled compound (containing 1.85 mCi of 3H-TCB). At day 1, the adrenal gland had the greatest concentration of radioactivity (dpm x 10( 6)/gm wet tissue) of any organ examined. There was a selective distribution of radiolabeled compound to the zona fasciculata accompanied by morphometric evidence of hypertrophy of the zona fasciculata. The vast majority of 3H-TCB present in the adrenal gland was parent compound at all time periods. Serum retinol content was significantly decreased in the high dose group by 61 and 54% at days 3 and 7, respectively. No significant decrease in adrenal gland retinoid content occurred at any time in this study, but in contrast, adrenal gland retinol and retinyl palmitate content was increased. Serum cortisol levels were transiently decreased in the high dose group. Ultrastructural alterations were only observed in cells of the zona fasciculata. Predominant changes included mitochondrial hypertrophy and concentric whorling lamellar arrays of the membranes of the outer mitochondrial compartment and mitochondrial cristae. The results of this study indicate that the rat adrenal gland is an early target organ after TCB intoxication, and that there is an early and selective distribution of TCB in the rat adrenal gland accompanied by morphologic alterations in the sites of compound localization. The results further suggest that the observed morphologic changes did not result from hypovitaminosis A. PMID- 2106056 TI - Differential sensitivity of head and neck cancers to non-major histocompatibility restricted killer cell activity. AB - Cell lines derived from squamous cell carcinoma of the upper aerodigestive tract (head and neck cancer) were phenotypically characterized with regard to differential sensitivity to nonmajor histocompatibility restricted (non-MHCr) killer cell activity. Requirements for detectable lysis of the cell lines in a standard chromium release assay included either isolation of fresh enriched Leu 19+ large granular lymphocytes (both Leu 19+CD3+ and Leu 19+CD3- populations) or interleukin-2 (IL-2) stimulation of peripheral blood lymphocytes (PBL). In neither circumstance could lytic activity be identified among Leu 19- populations. With PBL IL-2 stimulation significant differential sensitivity to lysis expressed by the head and neck cancer cell lines (P less than 0.001 by analysis of variance) was identified and maintained regardless of PBL source, i.e., PBL from healthy controls and three differing populations of head and neck cancer patients categorized by disease status and treatment. One factor associated with a cell line's increased sensitivity was degree of tumor differentiation, poorly differentiated tumors (as defined by intermediate filament cytochemical staining [decreased keratin and increased vimentin]) being more sensitive. Furthermore, as tumor cell lytic sensitivity increased, major histocompatibility complex (MHC)-class I antigen expression diminished concurrently. In 1 of 4 cell lines tested, however, pretreatment of tumor cells with interferon-gamma induced diminished lytic sensitivity independent of changes in MHC-class I expression, indicating factors not related to MHC-class I expression are likewise relevant. In previous studies we defined the in vivo prognostic significance of non-MHCr killer cell cytotoxicity activity against K562 targets, diminished activity being principally predictive of metastatic disease development in persons with poorly differentiated head and neck cancers. This report extends these observations by demonstrating in vitro that poorly differentiated head and neck cancer target cells are highly sensitive to changes in lytic function expressed by Leu 19+ non-MHCr effector cells. PMID- 2106057 TI - Long-term alpha-interferon therapy in myelodysplastic syndromes. AB - The myelodysplastic syndrome (MDS) is characterized by a high probability of leukemic transformation and frequently lethal infections or bleeding episodes. Up to now, no generally accepted form of therapy has been established for MDS. Previous trials with alpha-interferon (IFN-alpha) have shown some beneficial effects. We studied the effects of long-term application of IFN-alpha at higher dosages in patients with "low-risk" MDS. Ten patients were included in the study; eight were treated for a period of 6-36 months. IFN-alpha was administered at a median dosage of 9, 6, 4 mU/week during the first, second, and third year, respectively. Response was determined by the status of peripheral blood and bone marrow. Prolonged exposure to IFN resulted in a response rate of 3/10 (30%). In an additional case, disease progression was retarded during the third year of therapy. The incidences of infections and bleeding events subsided notably. After the withdrawal of IFN, hematological and clinical parameters rapidly deteriorated in some patients. The observed improvement of the patients' susceptibility to infections possibly prolongs their survival and seems to justify further trials on IFN treatment in patients with MDS. PMID- 2106058 TI - Activity of the hypothalamo-pituitary ovarian axis in hypothyroid rats with or without triiodothyronine replacement. AB - The hypothalamic pituitary ovarian axis in adult female rats with 131-I induced hypothyroidism was studied before and after triiodothyronine (T3) replacement. Forty days after 131-I, hypothyroid (H) rats showed irregular cycles with predominantly diestrous vaginal smears, atrophied and underweight ovaries, and decreased serum T3, T4, LH and estradiol (E2). T3 replacement restored normal cycles and ovary weight and increased serum E2 levels above control values, while LH levels remained below the limit of detection of the RIA. The GnRH stimulation test performed on the day that the rats exhibited diestrous vaginal smears elicited a greater increase in FSH than in LH in H rats and a greater increase in LH than in FSH in both H-T3 treated and control rats. The data suggest that the lack of thyroid hormones in adult female rats seems to produce a reversion of sexual hormones to a prepubertal pattern, while T3 treatment restored normal estrous cycles and ovarian function. PMID- 2106059 TI - Financial arguments and university education for nurses: a Canadian perspective. AB - Published information concerning costs of the various university disciplines is scanty, and Deans of Nursing have to rely on information that is transmitted to them by their university administrators. This paper provides some hard facts of comparative costs at one university, where, after an examination of the various factors involved, it was found that when judged by a) the cost of producing a section of a course, Nursing ranked 21 out of 28; b) the cost/student/section, regardless of level, Nursing ranked 19 out of 28; and c) the cost/student/section of the highest level undergraduate courses, Nursing ranked one out of 28. It was therefore concluded that financial arguments cannot be used to deprive nurses of the university education received by all other professionals. PMID- 2106060 TI - Mercury exposure from interior latex paint--Michigan. PMID- 2106061 TI - Imported dengue--United States, 1988. PMID- 2106062 TI - State tobacco-use prevention and control plans. PMID- 2106063 TI - Low birthweight--United States, 1975-1987. PMID- 2106064 TI - In situ localization and distribution of xenobiotic-activating enzymes and aryl hydrocarbon hydroxylase activity in lungs of untreated rats. AB - The present investigation was undertaken to more precisely establish where xenobiotics can be oxidatively metabolized and bioactivated within the lung. To accomplish this, antibodies raised against NADPH-cytochrome P-450 reductase (EC 1.6.2.4) and cytochromes P-450 BNF-B, PB-B, and PCN-E (the major forms of cytochrome P-450 induced by beta-naphthoflavone, phenobarbital, and pregnenolone 16 alpha-carbonitrile, respectively) that had been purified to apparent homogeneity from rat liver microsomes were used to determine the localizations and distributions of these enzymes immunohistochemically at the light microscopic level within lungs of untreated rats. Additionally, the intrapulmonary sites at which benzo(alpha)pyrene undergoes hydroxylation were identified in situ by means of fluorescence histochemistry. Immunohistochemical staining for NADPH-cytochrome P-450 reductase and cytochromes P-450 BNF-B, PB-B, and PCN-E was detected in bronchial epithelial cells, both ciliated and nonciliated (Clara) bronchiolar epithelial cells, and type II pneumocytes as well as other cells in the alveolar wall. Results of microfluorometric analyses of the immunofluorescence staining intensities of bronchial epithelial cells, Clara cells, and type II pneumocytes demonstrated further that Clara cells bound the antibodies raised to NADPH cytochrome P-450 reductase and cytochrome P-450 PB-B to significantly greater extents than did bronchial epithelial cells and type II pneumocytes. Thus, in lungs of untreated rats, Clara cells contain the greatest amounts of these two enzymes. In marked contrast, the antibodies directed against cytochromes P-450 BNF-B and PCN-E were each bound to similar extents by bronchial epithelial cells, Clara cells, and type II pneumocytes. In agreement with immunohistochemical observations on the intrapulmonary localizations of NADPH-cytochrome P-450 reductase and cytochromes P-450 BNF-B, PB-B, and PCN-E in untreated rats, benzo(alpha)pyrene was hydroxylated in situ by bronchial and bronchiolar epithelial cells and alveolar wall cells, especially type II pneumocytes. These immunohistochemical and histochemical findings, thus, demonstrate that bronchial epithelial cells, Clara and ciliated bronchiolar epithelial cells, and type II pneumocytes as well as other alveolar wall cells represent sites for the in vivo oxidative metabolism and bioactivation of xenobiotics in lungs of untreated rats. PMID- 2106065 TI - An inducible 50-kilodalton NF kappa B-like protein and a constitutive protein both bind the acute-phase response element of the angiotensinogen gene. AB - The rat angiotensinogen gene is induced in the course of the hepatic acute-phase response. We demonstrate that monocyte conditioned medium can stimulate transcription of a stably introduced reporter construct driven by 615 base pairs of the angiotensinogen 5'-flanking sequence, as well as the endogenous gene, in Reuber H35 cells. Point mutations of a cis-acting element, located 545 base pairs from the transcription start site and sharing sequence identity with known nuclear factor kappa B (NF kappa B)-binding sites, led to loss of cytokine inducibility. When cloned upstream of a minimal promoter, this cis-acting element imparted transcriptional inducibility by monocyte conditioned medium, interleukin 1, and tumor necrosis factor on a luciferase reporter gene in HepG2 cells. Two distinct proteins bound this element in vitro: a heat-stable, constitutively present, hepatic nuclear protein that gave rise to a DNase I-protected footprint covering the functionally defined element; and a binding protein of different mobility, induced by monocyte conditioned medium, which also recognized the NF kappa B-binding site of the murine kappa light-chain enhancer. UV cross-linking showed this inducible protein to have an apparent molecular mass of 50 kilodaltons, similar to that described for NF kappa B and distinct from the constitutively present protein that was shown by Southwestern (DNA-protein) blot to have a molecular mass of 32 kilodaltons. Methylation interference analysis showed that the induced species made contact points with guanine residues in the NF kappa B consensus sequence typical of NF kappa B. Induction of this binding activity did not require new protein synthesis, and 12-O-tetradecanoylphorbol-13 acetate could mimic the induction by cytokines. We thus provide direct evidence for involvement of NF kappa B or a similar factor in the hepatic acute-phase response and discuss the potential role of the presence of a constitutive nuclear factor binding the same cis element. PMID- 2106066 TI - Association of catalytic and regulatory subunits of cyclic AMP-dependent protein kinase requires a negatively charged side group at a conserved threonine. AB - In Saccharomyces cerevisiae, as in higher eucaryotes, cyclic AMP (cAMP)-dependent protein kinase is a tetramer composed of two catalytic (C) subunits and two regulatory (R) subunits. In the absence of cAMP, the phosphotransferase activity of the C subunit is inhibited by the tight association with R. Mutation of Thr 241 to Ala in the C1 subunit of S. cerevisiae reduces the affinity of this subunit for the R subunit approximately 30-fold and results in a monomeric cAMP independent C subunit. The analogous residue in the mammalian C subunit is known to be phosphorylated. Peptide maps of in vivo 32P-labeled wild-type C1 and mutant C1(Ala241) suggest that Thr-241 is phosphorylated in yeast cells. Substituting Thr-241 with either aspartate or glutamate partially restored affinity for the R subunit. Uncharged and positively charged residues substituted at this site resulted in C subunits that failed to associate with the R subunit. Replacement with the phosphorylatable residue serine resulted in a C subunit with wild-type affinity for the R subunit. Analysis of this protein revealed that it appears to be phosphorylated on Ser-241 in vivo. These data suggest that the interaction between R and C involves a negatively charged phosphothreonine at position 241 of yeast C1, which can be mimicked by either aspartate, glutamate, or phosphoserine. PMID- 2106067 TI - Immunoglobulin heavy-chain enhancer is required to maintain transfected gamma 2A gene expression in a pre-B-cell line. AB - The immunoglobulin heavy-chain (IgH) enhancer serves to activate efficient and accurate transcription of cloned IgH genes when introduced into B lymphomas or myelomas. The role of this enhancer after gene activation, however, is unclear. The endogenous IgH genes in several cell lines, for example, have lost the IgH enhancer by deletion and yet continue to be expressed. This might be explained if the role of the enhancer were to establish high-level gene transcription but not to maintain it. Alternatively, other enhancers might lie adjacent to endogenous IgH genes, substituting their activity for that of the lost IgH enhancer. To address both of these alternatives, we searched for enhancer activity within the flanking regions of one of these IgH enhancer-independent genes and designed an experiment that allowed us to consider separately the establishment and maintenance of expression of a transfected gene. For the latter experiment we generated numerous pre-B cell lines stably transformed with a gamma 2a gene. In this gene, the IgH enhancer lay at a site outside the heavy-chain transcription unit, between DH and JH gene segments. After expression of the transfected gene was established, selective conditions were chosen for the outgrowth of subclones that had undergone D-J joining and thus IgH enhancer deletion. Measurements of gamma 2a expression before and after enhancer deletion revealed that the enhancer was required for maintenance of expression of the transfected gene. The implication of this finding for models of enhancer function in endogenous genes is discussed. PMID- 2106068 TI - Serum stimulation of the c-fos enhancer induces reversible changes in c-fos chromatin structure. AB - Transcription of the proto-oncogene c-fos is known to be activated by growth factors in serum and subsequently repressed by the Fos protein. We show that generalized DNase I sensitivity of c-fos chromatin correlates closely with enhancer activity during induction, repression, and superinduction of the c-fos gene. Within 90 s of serum stimulation, proximal DNA sequences on both sides of the enhancer exhibit increased DNase I sensitivity. Within 5 min, elevated DNase I sensitivity spreads to chromatin at the distal 3' end of the c-fos gene. These results suggest that an open state of chromatin is propagated in both directions from the enhancer. The induced alterations in chromatin structure precede the increased transcriptional activity of the c-fos gene, suggesting that these changes in chromatin structure potentiate transcription. PMID- 2106069 TI - Inhibition of epidermal growth factor receptor biosynthesis caused by the src oncogene product, pp60v-src. AB - We have previously shown that an intracellular mechanism down regulates epidermal growth factor (EGF) receptor levels in rodent fibroblasts transformed by the src oncogene (W. J. Wasilenko, L. K. Shawver, and M. J. Weber, J. Cell. Physiol. 131:450-457, 1987). We now report that this down regulation is due to an inhibition of EGF receptor biosynthesis. With Rat-1 (R1) cells infected with a temperature-sensitive src mutant, we found that 125I-labeled EGF binding to cells began to decrease soon after the activation of pp60v-src by shift down to the permissive temperature for transformation. This effect of src on EGF receptors was reversible. Pulse-chase studies with [35S]methionine-labeled cells revealed that the tyrosine protein kinase activity of pp60v-src had little if any effect on EGF receptor degradation rate. By contrast, the expression of pp60v-src caused a large reduction in the apparent rate of EGF receptor biosynthesis. Northern (RNA) blot analysis demonstrated that pp60v-src also caused marked reductions in the steady-state level of EGF receptor mRNA. These data indicate that one way the expression of the src oncogene can affect the machinery of growth control is by affecting the expression of specific genes for growth factor receptors. PMID- 2106070 TI - Identification, nuclear localization, and DNA-binding activity of the zinc finger protein encoded by the Evi-1 myeloid transforming gene. AB - Activation of the Evi-1 zinc finger gene is a common event associated with transformation of murine myeloid leukemias. To characterize the gene product, we developed antisera against various protein domains. These antisera primarily detected a 145-kilodalton nuclear protein that bound double-stranded DNA. Binding was inhibited by chelating agents and partially restored by zinc ions. PMID- 2106071 TI - Octamer-binding proteins in diverse hemopoietic cells. AB - The immunoglobulin genes have B-cell-specific promoter and enhancer elements. The regulation of these elements is thought to be mediated to a large degree by the trans-activating factor oct-2, which binds the octamer element (ATTTGCAT). We have further examined the role of this octamer element in directing the lymphoid specific expression of the immunoglobulin H enhancer. No direct relationship was found between the levels of expression of the Cmu gene and oct-2. Indeed, variable amounts of oct-2 were detected in all of the hemopoietic lineage cells tested in this study. PMID- 2106072 TI - Two forms of Drosophila melanogaster Gs alpha are produced by alternate splicing involving an unusual splice site. AB - G proteins are responsible for modulating the activity of intracellular effector systems in response to receptor activation. The stimulatory G protein Gs is responsible for activation of adenylate cyclase in response to a variety of hormonal signals. In this report, we describe the structure of the gene for the alpha subunit of Drosophila melanogaster Gs. The gene is approximately 4.5 kilobases long and is divided into nine exons. The exon-intron structure of the Drosophila gene shows substantial similarity to that of the human gene for Gs alpha. Alternate splicing of intron 7, involving either use of an unusual TG or consensus AG 3' splice site, results in transcripts which code for either a long (DGs alpha L) or short (DGs alpha S) form of Gs alpha. These subunits differ by inclusion or deletion of three amino acids and substitution of a Ser for a Gly. The two forms of Drosophila Gs alpha differ in a region where no variation in the primary sequence of vertebrate Gs alpha subunits has been observed. In vitro translation experiments demonstrated that the Drosophila subunits migrate anomalously on sodium dodecyl sulfate-polyacrylamide gels with apparent molecular weights of 51,000 and 48,000. Additional Gs alpha transcript heterogeneity reflects the use of multiple polyadenylation sites. PMID- 2106073 TI - Development of a method to increase the proportion of polychromatic erythrocytes from mouse bone marrow for more rapid evaluation of the micronucleus assay. Comparison with the conventional method with respect to micronucleus frequency and time required for preparation and evaluation. AB - By treatment of bone marrow suspension in hypotonic (0.51%) saline, followed by purification on a cellulose column, the proportion of polychromatic erythrocytes in bone marrow smears can be increased 2.6-fold. Furthermore, practically all nucleated cells of erythropoietic or leukopoietic origin are removed. This kind of bone marrow preparation can lead to a considerable reduction in the time required for microscopical evaluation of the micronucleus assay without altering the rate of micronucleated polychromatic erythrocytes in a negative (isotonic saline) and a positive (mitomycin C) control group. PMID- 2106074 TI - The N-linked carbohydrate chain of the 85-kilodalton glycoprotein from Trypanosoma cruzi trypomastigotes contains sialyl, fucosyl and galactosyl (alpha 1-3)galactose units. AB - The structure of the N-linked oligosaccharide of the 85-kDa surface glycoprotein (Tc-85) from the infective trypomastigote form of Trypanosoma cruzi was investigated. Tc-85 metabolically labeled with [14C]glucose was purified by affinity chromatography on wheat germ agglutinin-Sepharose. Binding to the lectin was lost on treatment of Tc-85 with neuraminidase. The N-linked asialo oligosaccharide was released by endo-beta-N-acetylglucosaminidase F digestion of asialo-Tc-85 and was further analyzed using specific exoglycosidases. [14C]fucose was detected after alpha-L-fucosidase treatment or mild acid hydrolysis. The afucosyl oligosaccharide was 3H-labeled by the galactose oxidase-NaB3H4 method. [3H]Galactose was released by alpha-galactosidase, and only then was beta galactosidase effective in removing another galactose. The gal(alpha 1-3)gal unit was demonstrated by periodate oxidation studies on the [3H]galactose-labeled asialo-glycoprotein. The presence of gal(alpha 1-3)gal in Tc-85 could be related to the recent finding of elevated antibody levels against this epitope in patients with Chagas' disease. PMID- 2106075 TI - Monoclonal antibodies against the flagellar fraction of epimastigotes of Trypanosoma cruzi: immunoprotection against metacyclic trypomastigotes obtained by immunization of mice with an affinity-purified antigen. AB - Subcellular fractions of Trypanosoma cruzi (epimastigotes) were assayed in their capacity to induce protective or aggressive effects in experimental animals. The flagellar fraction showed the best immunoprotective properties without tissular aggression. Monoclonal antibodies were prepared from mice immunized with this fraction. One of them, FCH-F8-4, was able to neutralize the infectivity of bloodstream trypomastigotes, to produce complement-mediated lysis on cell culture derived trypomastigotes and to recognize the surface of trypomastigotes and epimastigotes by immunofluorescence. FCH-F8-4 reacted in Western blotting with several epimastigote proteins ranging from 50 to 150 kDa, showing a more intense reactivity with 4 bands while it reacted with two molecules on trypomastigote preparations (15 and 48 kDa). Purified antibody was coupled to CNBr-activated Sepharose and used to purify antigens from epimastigote extracts. These antigens were used to immunize BALB/c mice in the presence of Bordetella pertussis as adjuvant. Animals were protected against a challenge with 10(3) metacyclic forms of T. cruzi (Tulahuen strain). Only 40% of immunized mice presented detectable parasites in blood after challenge. Parasitemia decreased 90% in relation to controls in those animals. Survival of immunized mice was 100% in all immunoprotection experiments. These results suggest that the epitope recognized by FCH-F8-4 present in the purified antigens keeps the protective characteristics of flagellar fraction and could be a candidate for the development of a vaccine against T. cruzi infection. PMID- 2106076 TI - The stage-specific 90-kilodalton surface antigen of metacyclic trypomastigotes of Trypanosoma cruzi. AB - The 90-kDa antigen, previously identified by the monoclonal antibody 1G7 to be a stage-specific surface protein of metacyclic trypomastigotes of Trypanosoma cruzi, has been further characterized in this study. Experiments of metabolic labeling with [35S]methionine, [2H]mannose and [3H]galactose revealed that the 90 kDa antigen is the main glycoprotein synthesized by metacyclic forms (G strain). Through pulse-chase experiments with [35S]methionine-labeled metacyclic trypomastigotes, it was found that the antigen is synthesized as a 75-kDa precursor polypeptide that is rapidly processed to the mature 90-kDa molecule. When metacyclic trypomastigotes were treated with tunicamycin, the production of 90-kDa antigen was greatly diminished, and the 75-kDa species, which was also expressed on the cell surface, accumulated. Concanavalin A bound strongly to the 90-kDa antigen, but failed to recognize the 75-kDa polypeptide. Treatment of neuraminidase had no effect on the 90-kDa antigen, whereas digestion by endoglycosidase H generated a polypeptide of 82 kDa. Altogether these data indicate that the 90-kDa antigen is a glycoprotein containing N-linked oligosaccharide side chains of the high-mannose type. The 90-kDa glycoprotein may be involved in the process of host cell invasion, since the internalization of metacyclic forms into Vero cells was partially inhibited by monoclonal antibody 1G7. PMID- 2106077 TI - Cost effectiveness of bone marrow transplantation. PMID- 2106078 TI - Animal rights: Silver Spring. "Valuable data" claim. PMID- 2106079 TI - Structure of human pancreatic lipase. AB - Pancreatic lipase (triacylglycerol acyl hydrolase) fulfills a key function in dietary fat absorption by hydrolysing triglycerides into diglycerides and subsequently into monoglycerides and free fatty acids. We have determined the three-dimensional structure of the human enzyme, a single-chain glycoprotein of 449 amino acids, by X-ray crystallography and established its primary structure by sequencing complementary DNA clones. Enzymatic activity is lost after chemical modification of Ser 152 in the porcine enzyme, indicating that this residue is essential in catalysis, but other data are more consistent with a function in interfacial recognition. Our structural results are evidence that Ser 152 is the nucleophilic residue essential for catalysis. It is located in the larger N terminal domain at the C-terminal edge of a doubly wound parallel beta-sheet and is part of an Asp-His-Ser triad, which is chemically analogous to, but structurally different from, that in the serine proteases. This putative hydrolytic site is covered by a surface loop and is therefore inaccessible to solvent. Interfacial activation, a characteristic property of lipolytic enzymes acting on water-insoluble substrates at water-lipid interfaces, probably involves a reorientation of this flap, not only in pancreatic lipases but also in the homologous hepatic and lipoprotein lipases. PMID- 2106080 TI - [A case of recurrence of a metastatic brain tumor which disappeared due to chemotherapy only]. AB - A rare case of recurrence of a metastatic brain tumor which disappeared due to chemotherapy only is reported. A 52-year-old male was noticed to have an abnormal shadow in his chest X-P at a routine medical examination, so a close examination was made. He was diagnosed as having right renal cell carcinoma which had metastasized to the lung. He was treated by intra-arterial infusion of anti cancer drugs and embolization of the right renal artery. No renal symptom was seen, growth of the primary tumor stopped, and the abnormal shadow in his chest diminished. However, weakness in the left hand appeared 19 months after the first examination and he was admitted to our clinic. He was alert, but slight left hand weakness was observed. CT scan revealed a diffusely enhanced mass in the right parietal lobe. Total removal of the brain tumor was performed and the histology was metastasis of renal cell carcinoma. He was discharged and was able to walk but he had slight left hemiparesis. UFT 6 capsules a day were administrated in our out-patient clinic. However, CT scan revealed recurrence of the tumor 2 weeks after discharge, we followed up with conservative treatment, and no growth of the tumor was seen. It disappeared 5 months after discharge after being treated with UFT only. We regard UFT as having been effective in this case. PMID- 2106081 TI - Hypothalamo-pituitary disconnection in the fetal sheep. AB - In this study we have applied the technique of hypothalamo-pituitary disconnection (HPD) to the fetal sheep at 108-112 days of gestation. The pituitary is surgically disconnected from the hypothalamus by the removal of the neural component of the median eminence above the level of the portal circulation. This procedure results in the complete disconnection of the pituitary from the hypothalamus. After HPD, the lactotroph response to the dopamine antagonist chlorpromazine was significantly reduced (p less than 0.005) indicating the functional isolation of the pituitary gland from the hypothalamus. The increase in plasma prolactin in response to exogenous thyrotrophin-releasing factor was maintained following HPD. HPD resulted in the complete atrophy of the pars nervosa. At 132-135 days of gestation after HPD there was no change in the volume or appearance of the pars distalis; small infarcts were observed in the pars distalis of some HPD fetuses, but these occupied less than 1% of the volume of the anterior lobe of the pituitary. There was a significant increase (p less than 0.05) in the volume of the pars intermedia after HPD. Gestation was prolonged for at least 8 days beyond normal term following HPD, indicating that the processes integral to the initiation of parturition at term had been disrupted. We conclude that HPD provides a good in vivo model for the investigation of the activity of the isolated pituitary gland, and for the examination of the role of neuroendocrine mechanisms in fetal sheep development in the latter third of gestation. PMID- 2106082 TI - Localization of immunoreactive glandular kallikrein in lactotrophs of the rat anterior pituitary. AB - Glandular kallikrein (a trypsin-like serine protease) is an estrogen-induced and dopamine-repressed protein in the rat anterior pituitary which predominantly exists as a latent zymogen (prokallikrein). Its regulation, presence in estrogen induced pituitary tumors in F344 rats, and expression in GH3 cells has suggested a localization in lactotrophs (prolactin-producing cells). This study examined the cellular origin of glandular kallikrein using immunocytochemical techniques. Anterior pituitaries from estrogen-treated rats were fixed and embedded in paraffin (for preparation of semi thick sections; 5 microns) or methacrylate (for preparation of thin sections; 1 micron). Glandular kallikrein immunostaining was readily detected in the perinuclear (Golgi) region of parenchymal cells of the anterior pituitary in both thin and semi thick sections. Two-color double immunoperoxidase staining of thin and semi thick sections indicated that glandular kallikrein was localized in cells containing prolactin (PRL) but not other pituitary hormones. Immunoperoxidase staining of consecutive serial thin sections with alternating antisera confirmed a localization of glandular kallikrein in lactotrophs. The results establish that glandular kallikrein is colocalized with PRL in lactotrophs of the rat anterior pituitary. This is consistent with the hypothesis that the function of anterior pituitary glandular kallikrein is linked to PRL in some fashion--possibly as a PRL-processing protease. PMID- 2106083 TI - Cocaine disrupts estrous cyclicity and alters the reproductive neuroendocrine axis in the rat. AB - Although a common drug of abuse, cocaine's effects on cyclic reproductive functions and the neuroendocrine systems regulating these functions have not been studied. Here, we report the effects of cocaine on (1) estrous cyclicity and ovulation rates and (2) the stimulated in vitro release of hypothalamic GnRH and aminergic neurotransmitters directly involved in regulating or modulating GnRH release. Within 7 days of treatment with 10 mg kg-1 day-1 of cocaine HCl subcutaneously, rats demonstrated significant estrous cycle irregularity including repetitive days of estrus and prolonged periods of diestrus. After 6 weeks of treatment, cocaine-treated rats exhibited a 44.3% decrease in ovulation rates. For the in vitro studies, bilaterally ovariectomized rats were injected with cocaine (10 mg kg-1 day-1) or with saline for 2 weeks. Each rat received estradiol benzoate (50 mg kg-1 day-1 s.c.) for 2 days before sacrifice. Hypothalamic slices were prepared, placed in 0.1 ml microchambers and perfused with modified Krebs buffer (pH 7.4) using a programmable perfusion system. Basal release of norepinephrine (NE) and serotonin (5HT) was significantly increased in the cocaine-treated group versus controls. Ten-minute pulses of 10(-7)M progesterone (P4) increase NE and 5HT, but not dopamine (DA), release in the saline-treated group. In contrast, pulses of P4 increased NE, but not 5HT or DA, in the cocaine-treated rats. Ten-minute pulses of 0.1 microM NE increased GnRH release in both saline- and cocaine-treated rats. However, the response to pulsed NE was significantly attenuated in the cocaine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106084 TI - Regional distribution of neuropeptide Y-like immunoreactivity in human hypothalamus measured by immunoradiometric assay: possible influence of chronic respiratory failure on tissue levels. AB - The regional distribution of neuropeptide Y-like immunoreactivity (NPY-IR) in the human hypothalamus has been determined using a highly specific immunoradiometric assay. Hypothalami were removed during postmortem examination from 19 subjects. The pituitary stalk and 11 anatomically defined nuclei and areas were microdissected from one or both sides of each hypothalamus. NPY-IR was detectable in the acid extracts of tissue samples prepared from all the hypothalamic regions studied, with the highest concentrations being found in the infundibular nucleus (325 +/- 53 fmol/mg wet weight of tissue) and the ventromedial nucleus (217 +/- 22 fmol/mg). For the 11 subjects where both sides of the hypothalamus were dissected, values obtained for the areas in one half showed a good degree of symmetry with the corresponding areas on the contralateral side. The infundibular nucleus exhibited the greatest range of values (72-1,137 fmol/mg). Interestingly, variations in other parts of the hypothalamus were observed to parallel those of this nucleus. Expressed as correlation coefficients (r), levels in the infundibular nucleus appeared to be most closely related to those of the ventromedial nucleus (VM; r = 0.89) and paraventricular nucleus (PV; r = 0.84). In addition, retrospective analysis of the clinical histories showed that all patients with very high NPY levels in the infundibular nucleus (621.0 +/- 107.7 fmol/mg; n = 8) had suffered from respiratory failure or severe dyspnea of at least 10 days duration prior to death. The remaining patients (166.7 +/- 17.1 fmol/mg; n = 11) had either died 48 h from the onset of cardiorespiratory difficulties or of unrelated causes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106085 TI - Prolactin circadian rhythm persists throughout lactation in women. AB - To determine whether the prolactin (PRL) circadian rhythm, with its characteristic nocturnal rise, persists during the hyperprolactinemia of lactation, PRL levels were analyzed in blood samples collected hourly for 24 h from 20 mothers, 4-46 months postpartum. The circadian rhythm of PRL persisted throughout lactation as manifested by: (1) significantly higher mean nighttime than daytime PRL levels in the whole sample, despite higher daytime nursing durations; (2) the distribution of zenith levels which most frequently occur between 23.00 and 07.00 h, when nursing duration is lowest, and which are almost absent between 07.00 and 23.00 h, when nursing duration is highest, and of nadir levels, which have an opposite pattern; (3) spontaneous PRL surges that are more frequent, longer, and of higher magnitude at night than during the day, and (4) the larger magnitude of suckling-induced PRL release from late afternoon through the night compared to the morning in some women. Our data suggest that the mechanisms responsible for the circadian rhythm in PRL secretion are relatively independent of the mechanisms of suckling-induced release. We propose that the nocturnal rise in PRL during lactation functions to ensure a robust milk supply during an extensive nonsuckling interval. PMID- 2106086 TI - Site-dependent action of intracerebroventricular 5-hydroxytryptamine on the cold stimulated thyrotropin secretion in male rats. AB - The effects of central 5-hydroxytryptamine (5-HT) infusions on the cold stimulated thyrotropin (TSH) levels were studied in male rats. Stainless-steel cannulas were implanted stereotaxically into the anterior or the posterior third ventricle or just lateral to the hypothalamic paraventricular nuclei bilaterally 7 days before experiments. Infusion of 5-HT (4.5 and 9 micrograms/rat) into the posterior third ventricle attenuated significantly the cold-stimulated TSH levels. Inversely, infusion of 5-HT (9 micrograms/rat) into the anterior third ventricle augmented significantly the TSH cold response. Bilateral 5-HT infusions into the vicinity of the hypothalamic paraventricular nuclei did not affect the TSH cold response. Serum prolactin levels increased significantly after 5-HT administration into the anterior and the posterior third ventricle, but no consistent effect on growth hormone (GH) levels could be detected. Infusion of 5 HT into the anterior and the posterior third ventricle decreased body temperature irrespective of the observed hormonal response to 5-HT. The results are in favor of a dual and possibly site-dependent role for 5-HT in the regulation of the cold stimulated TSH secretion in the rat. The opposite effects of 5-HT on the TSH cold response may result from the predominant inhibition of either the thyrotropin releasing hormone or the somatostatin-secreting cell groups. PMID- 2106087 TI - Dual and selective actions of glucocorticoids upon basal and stimulated growth hormone release in man. AB - In humans, corticoids suppress growth and growth hormone (GH) secretion elicited by a variety of stimuli, while in the rat they potentiate both in vivo and in vitro GH release. To further study this problem, growth-hormone-releasing hormone (GHRH) tests were performed in 6 nonobese Cushing's syndrome patients and 6 controls. The normal GHRH-induced GH secretion was completely abolished in the Cushing's syndrome group. To study the action of shorter corticoid exposures, 34 volunteers were subjected to four tests each: placebo treatment (control); dexamethasone (Dex) administration 4 mg i.v., 3 h before; Dex 8 mg p.o., 12 h before, and Dex 22 mg p.o. over the 2 days before the pituitary challenge that was always administered at 0 min (12.00 h). In the first test (n = 9), GHRH (1 microgram/kg i.v.) induced a GH peak of 14.5 +/- 3.8 ng/ml (control) that was potentiated by Dex 4 mg i.v. administered 3 h before (26.4 +/- 6.8 ng/ml). On the contrary, longer Dex treatments suppress GHRH-induced GH values (6.0 +/- 1.1 ng/ml after Dex 8 mg and 1.8 +/- 0.3 ng/ml after Dex 22 mg). Clonidine administration 300 micrograms p.o. (n = 7) increased GH secretion with an area under the secretory curve (AUC) of 1,274 +/- 236 that was potentiated by Dex 4 mg i.v. given 3 h before clonidine (2,380 +/- 489) and reduced by Dex 8 mg, the reduction being significant only after 22 mg Dex (595 +/- 47).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106088 TI - Homeostatic thymus hormone stimulates corticosterone secretion in a dose- and age dependent manner in rats. AB - There is increasing evidence that the neuroendocrine system is responsive to hormonal signals generated by the immune systems. In particular, interleukin-1 and thymosin have been shown to stimulate the pituitary-adrenal axis in young animals. We report here that homeostatic thymus hormone (HTH), a well characterized thymic preparation, increases plasma levels of corticosterone but not prolactin (PRL) in a dose- and age-dependent manner in male Sprague-Dawley rats. Young (3 months) and old (26 months) conscious, free-moving animals carrying an indwelling atrial cannula received the substances to be tested via the cannulas. Plasma samples were taken every 30 min for 5 h and hormones were measured by radioimmunoassay. HTH doses of 1 and 8 mg/kg body weight injected into young rats elicited a 7.8- and 12.8-fold increase in plasma corticosterone, respectively, as compared to saline-injected controls. The HTH-induced peak corticosterone levels were reached within 1.5 and 2.5 h after HTH injection. Plasma PRL was not affected by HTH in either age group. A single dose of 8 mg HTH/kg body weight induced a smaller corticosterone response in old than in young rats, although the time course of the response was similar in both age groups. The present results further suggest the existence of a lymphoid-neuroendocrine axis in young animals. The data also suggest that a disruption in immune endocrine integration occurs during aging in rats. PMID- 2106089 TI - Effects of ethanol during the onset of female puberty. AB - To assess more closely the physiological mechanism(s) by which ethanol (ETOH) delays the onset of female puberty, we have evaluated its effects on body weight, the vaginal opening (VO)-first diestrus (D1) interval and the serum concentrations of growth hormone (GH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) throughout the peripubertal period in the rat. Using a specific intragastric feeding regimen, 29-day-old rats began receiving either a liquid diet containing ETOH or an isocaloric control liquid diet. Additional controls consisted of animals maintained on laboratory chow and water provided ad libitum. Animals were either killed between 32 and 37 days of age, categorized with regard to their phase of puberty and their serum hormones measured; or, in some animals, the ETOH liquid diet was administered through day 41 and at that time replaced by the control liquid diet in order to determine if recovery would occur. Our results indicate that ETOH-treated animals showed significantly lower body weights and a significantly longer mean VO-D1 interval than the control animals. Also, serum GH and LH levels were significantly lower in the ETOH treated animals; however, FSH levels were not affected. Administration of the ETOH liquid diet through day 41 produced varying detrimental effects on the onset of puberty and subsequent removal of ETOH from the diet resulted in rapid growth of the animals, followed by the onset of puberty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106090 TI - Effect of adrenalectomy and demedullation on the stress-induced impairment of long-term potentiation. AB - In these three experiments, we investigated the effect of adrenalectomy and adrenal demedullation on the stress-induced impairment of long-term potentiation (LTP) in the rat hippocampal slice. In the first, adrenalectomy alone resulted in a significant reduction in LTP, while exposure to stress resulted in a further reduction. In the second, replacing corticosterone in adrenalectomized rats did not restore LTP. In the last experiment, demedullation resulted in a reduction in LTP similar to that induced by adrenalectomy, while exposure to stress did not result in a further reduction. In combination, these studies provide evidence that the adrenal medullary system modulates hippocampal plasticity and the stress induced impairment of LTP. PMID- 2106091 TI - Growth hormone-deficient young adults have decreased deep sleep. AB - The sleep in young adults with severe isolated growth hormone deficiency (IGHD) was examined by polysomnography. There was a significant decrease in delta sleep time (= stages 3 + 4, slow wave sleep, 'deep sleep'), especially in stage 4. The total sleep time was significantly increased compared to age- and sex-matched normal subjects. The increase in total sleep time was related to an increase in stage 1 and stage 2 sleep. There was no significant difference in total rapid eye movement (REM) sleep time, but when correcting for the very long sleep time in the IGHD subjects, the cumulated REM time within the first 390 min of sleep was significantly less than in the normal subjects. PMID- 2106092 TI - Depletion of hypothalamic growth hormone-releasing hormone by neonatal monosodium glutamate treatment reveals an inhibitory effect of betamethasone on growth hormone secretion in adult rats. AB - Rats were treated with monosodium glutamate (MSG), 4 mg/g on alternate days for the first 10 days of life, to induce lesions of the arcuate nucleus and destroy the majority of growth hormone-releasing hormone (GHRH) neurones. At 10 weeks of age, control (n = 42) and MSG-treated (n = 36) male rats were used to test the effect of glucocorticoids on growth hormone (GH) secretion. Each treatment group was divided into six study groups to determine the effect of betamethasone (BM), administered either 3 or 20 h prior to sacrifice, alone and in combination with hypoglycaemia (insulin 0.1 U/100 g). BM treatment of male rats was without effect on plasma GH levels in control animals. In contrast, glucocorticoid administered either 3 h before sacrifice or the previous evening significantly reduced circulating GH (p less than 0.001) in MSG-treated animals. The difference in plasma GH response to BM pretreatment in control rats and those with lesions of the arcuate nucleus indicates a hypothalamic action of glucocorticoids, presumably on somatostatin and GHRH neurones. In control animals the effects appear to be counterbalancing, but following destruction of GHRH neurones an uncompensated inhibitory influence was observed. Male MSG-treated rats had lower body weight (-25%) and reduced hypothalamic GHRH (-89%) and pituitary GH content (-69%) compared to male controls. Female rats which had undergone the same neonatal MSG treatment (n = 40) when sacrificed 1 week after their male counterparts showed similar reductions in body weight (-15%), hypothalamic GHRH ( 74%), and pituitary GH (-67%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106093 TI - Plateau potentials recorded from lactating rat enriched lactotroph cells are triggered by thyrotropin releasing hormone and shortened by dopamine. AB - Enrichment of dispersed pituitary cells from normal lactating rats on a continuous BSA gradient permitted the isolation of two prolactin cell populations -light and heavy. Hormone release studies indicated that spontaneous prolactin (PRL) release of the heavy fraction cells was particularly sensitive to TRH stimulation (mean of 450%) and that this effect of TRH was totally inhibited by Ca2+ channel blockers (Co2+, Cd2+, Ni2+ and Mn2+). For this reason, the electrophysiological response to TRH was investigated on heavy fraction cells. Experiments performed on 264 cells after 4-12 days in culture showed that these cells could be divided into two groups. The first group, called high resting potential (HRP) cells, constituted 73% of the total and was characterized by a mean resting potential of -60 mV and a mean input membrane resistance of 700 M omega, and these cells displayed plateau potentials, which were triggered by application of brief (2 s), large (1 nA) depolarizing or hyperpolarizing current steps. The plateaux were characterized by a sustained depolarization at a potential near -20 mV and they were concomitant with an increase of the membrane conductance. The repolarization consisted of a slight, gradual hyperpolarization followed by a rapid return to the resting potential. The second group of cells (the remaining 27%; called low resting potential or LRP cells) was characterized by a mean resting potential of -45 mV and a mean input membrane resistance of 250 M omega. These cells were excitable, 30% of them displaying spontaneous activity but never showing plateaux. Electrophysiological experiments showed that the majority of the HRP cells (99%) responded to TRH but were insensitive to dopamine (DA) ejections (up to 10(-6) M) at resting potential. Ejection of TRH onto HRP cells induced a slow depolarization (10-15 mV) concomitant with a decrease of the membrane resistance. This led the cell membrane potential to a critical value (approximately -50 mV), at which the plateau response was triggered. The plateau lasted for about 10 s from potentials greater than -100 mV, and could reach 10 min from holding potentials close to the resting potential. The amplitude of the plateau varied according to the holding potential and the reversal potential was found to be -20 mV. Local application of tetraethylammonium chloride (TEA, 30 mM) only slightly affected the amplitude of the plateaux but they were shortened or totally blocked by Co2+, Cd2+ and Ni2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2106094 TI - Light-induced changes in pineal gland N-acetyltransferase activity: developmental aspects. AB - In adult rats, light acting via a retino-pineal gland neural pathway influences pineal gland biochemistry in two ways: (1) it entrains endogenous circadian rhythms in melatonin biosynthesis to the environmental photoperiod and (2) exposure to even very brief periods of light during the nighttime rapidly suppresses the high levels of nocturnal melatonin production. The present studies were undertaken to determine precisely when photic stimulation first influences the enzymic activity of N-acetyltransferase (NAT), the pineal gland enzyme which rate-limits the overall biosynthesis of the hormone melatonin, and to examine some of the cellular mechanisms which might mediate light-induced effects in neonatal animals. Rats of different ages were either killed during the light phase or were exposed to darkness or light for 1 min during the dark phase of the lighting cycle, returned to their litters in darkness for 30 min and then killed. Pineal gland NAT activity in animals nocturnally exposed to 1 min of light was suppressed in animals 6 days of age or older. Nocturnal light exposure did not suppress enzyme activity in 3- to 5-day-old rats, even though these animals displayed clear light:dark differences in pineal gland NAT activity. Nocturnal light exposure also did not suppress nighttime levels of NAT activity in 7-day old animals who had been bilaterally enucleated, suggesting that this effect is retinally mediated. Pretreatment of 7-day-old animals with the beta noradrenoceptor agonist drug, isoproterenol, prevented the nocturnal light induced suppression of NAT activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106095 TI - Patterns of pineal melatonin secretion in rabbits: diurnal variation of basal and pulsatile release. AB - The level and release pattern of plasma melatonin in the confluens sinuum of 28 sighted and 18 blinded (i.e. acute bilateral orbital enucleation) rabbits anesthetized with pentobarbital were studied. The animals had been adapted to a 12:12 h light-dark regime. Blood samples were collected from the cannulated confluens sinuum and/or the femoral artery at either 2- or 4-min intervals in both the light and dark phases. Plasma melatonin was determined by radioimmunoassay. In all rabbits studied, plasma melatonin in the confluens sinuum exhibited an episodic release pattern, with pulses superimposed on a basal level. At 4-min sampling intervals, the pulsatile release of melatonin in sighted rabbits were 3.8 peaks/h in the light phase; shorter sampling interval (2-min) revealed more frequent pulsatile release of melatonin (5.1 peaks/h). In sighted animals in the light phase, the level of melatonin in the plasma of confluens sinuum was 7-15 times higher than that obtained from the plasma collected at the same time from the peripheral artery where the level of melatonin also exhibited pulsatile pattern. In blinded animals, melatonin levels in terms of mean concentration, mean maximum level and mean minimum (or baseline) level obtained in the dark phase were 12-14 times higher than those obtained in the light phase. These results suggest that the level of melatonin exhibits a diurnal rhythm in the confluens sinuum of rabbits. PMID- 2106096 TI - Passive avoidance behavior, vasopressin and the immune system. A link between avoidance latency and immune response. AB - The relation between passive avoidance behavior and primary antibody response was studied in rats. The avoidance latency was varied by means of variation of the shock intensity during the learning trial; a higher shock intensity resulted in a longer avoidance latency at the retention test. The avoidance latencies were inversely proportional to the magnitude of the primary antibody response. Neuropeptides, such as [Arg8]-vasopressin (AVP) were shown to potentiate retrieval processes. Administration of 10 ng desglycinamide AVP (DGAVP) 1 h prior to the retention test facilitated passive avoidance behavior (increase in avoidance latency). Conversely i.c.v administration of vasopressin antiserum resulted in attenuation of the avoidance behavior. The effects of altered passive avoidance behavior as a consequence of i.c.v. administration of DGAVP or vasopressin antiserum were studied on the primary antibody response. Again an inversely proportional relationship between the avoidance latency and the magnitude of the primary antibody response was observed. The results show that the immune system can specifically react to graded environmental stimuli. It is hypothesized that vasopressin may be an endogenous mediator determining the outcome of the avoidance behavior and the primary antibody response. PMID- 2106097 TI - Electrophysiological evidence for a key control function of the medial preoptic area in the regulation of prolactin secretion in cycling, pregnant and lactating rats. AB - Female rats were chronically fitted with stainless steel electrodes in the medial preoptic area (MPOA), together with a chronic atrial blood sampling/blood transfusion catheter. The surgery did not affect cyclicity, pregnancy or lactation. Twenty-five minutes of bilateral electrical stimulation (100-Hz voltage pulses, 0.2 ms width, 10 s on/5 s off) of the MPOA significantly reduced the magnitude of the proestrous and estrous afternoon levels of prolactin (Prl) in cycling rats, the nocturnal and diurnal levels of Prl in pregnant rats as well as Prl secretion during suckling in lactating rats. These data demonstrate that the MPO exerts dominant inhibitory control over all known surges of Prl secretion in female rats and may be considered as 'antisurge key control center' for Prl secretion. A functional role of the sexually dimorphic nucleus in the control of Prl secretion is suggested. PMID- 2106098 TI - Modulatory effect of testosterone on the serotoninergic control of prolactin secretion in prepubertal rats. AB - The administration of 5-hydroxytryptophan (5-HTP) induced a prolactin release in male and female prepubertal rats at 20 days of age. This response was significantly higher in male than in female rats. Neonatal androgenization of the females significantly increased the release of prolactin induced by 5-HTP treatment compared to the values observed in males; thus, the neonatal exposure to androgens seems to be responsible for the sexual differences in the prolactin response to 5-HTP. In a second series of experiments the effect of this serotoninergic precursor on prolactin release in prepubertal (16, 26, and 30 days of age), peripubertal (45-day-old) and adult male rats was studied. Castration significantly decreased the prolactin release response to 5-HTP in prepubertal rats. The administration of testosterone to castrated rats markedly increased the prolactin release response to 5-HTP. Neither castration nor testosterone administration modified the prolactin response to 5-HTP in peripubertal and adult rats. These results appear to indicate that testosterone modulates the serotoninergic control of prolactin secretion during the prepubertal stage. The control of prolactin levels could be one of the mechanisms by which testosterone participates in the sexual maturation. PMID- 2106100 TI - The gonadotropin-releasing hormone neuronal system of the male Djungarian hamster: distribution from the olfactory tubercle to the medial basal hypothalamus. AB - The neuroanatomical distribution and morphology of neurons that produce gonadotropin-releasing hormone (GnRH) in the brain of the postpubertal male Djungarian hamster was studied using light microscopic immunocytochemistry. Analysis of every section from the rostral olfactory tubercle to the medial basal hypothalamus indicate 356 +/- 37 immunoreactive GnRH perikarya per brain (mean +/ SE; n = 4 brains). Over 90% of GnRH cell bodies were found in 6 brain regions; the largest number of somata were located in the medial preoptic area followed by the diagonal band, lateral hypothalamus, lateral preoptic area, lateral septum and anterior hypothalamus. Morphologically, two predominant types of GnRH neurons were identified: unipolar GnRH cells with an ovoid soma and only a single distinct process (about 40% of all GnRH neurons), and bipolar cells with a fusiform-shaped perikaryon. Overall and in most brain regions, the ratio of unipolar to bipolar GnRH perikarya was 2:3 or greater. A significant proportion of GnRH neurons had an unusually "thick" process(es) that exited the soma and tapered gradually. GnRH fibers were evident in most sections, forming dense plexuses in the arcuate nucleus-median eminence, the periventricular region of the third ventricle and organum vasculosum of the lamina terminalis. These findings indicate that the Djungarian hamster is similar to other rodent species, especially the white-footed mouse, in the neuroanatomical distribution of GnRH neurons. The present report provides a working atlas for the rostral ventral forebrain of the postpubertal Djungarian hamster.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106099 TI - Stress-induced suppression of the prolactin afternoon surge in ovariectomized, estrogen-treated rats and the nocturnal surge in pseudopregnant rats are accompanied by an increase in median eminence dihydroxyphenylacetic acid concentrations. AB - Experiments were performed to determine whether the suppression of prolactin (PRL) surges during restraint was accompanied by changes in the activity of tuberoinfundibular dopamine (TIDA) neurons in the median eminence. Animals were either ovariectomized and estrogen-treated (OVX-PEP) or cervically stimulated to induce pseudopregnancy (PSP). Restraint stress was administered by tying the hind legs together with plastic-coated bell wire. Animals were decapitated following 15 or 30 min of restraint stress or immediately after removal from the animal room (control) when PRL levels were basal (10.00 h), at the peak of the afternoon PRL surge in OVX-PEP animals (17.00 h) or the nocturnal PRL surge in PSP animals (05.00 h). Median eminence dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) were significantly decreased in control rats at 17.00 h when compared to control rats at 10.00 h (103.1 +/- 3.7 vs. 85.8 +/- 3.3 and 11.4 vs. 7.1 +/- 0.4 pg/micrograms protein, respectively) and plasma PRL was markedly elevated. Restraint stress at 10.00 h resulted in a significant increase in serum PRL, but this increase was not accompanied by a change in DA or DOPAC when compared to control animals (103.1 +/- 3.7 vs. 107.9 +/- 4.8 and 11.4 +/- 0.4 vs. 10.4 +/- 0.6 pg/micrograms protein, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106101 TI - Occurrence of hydrin 2 (vasotocinyl-Gly), a new hydroosmotic neurohypophyseal peptide, in secretory granules isolated from the frog (Rana esculenta) neurointermediate pituitary. AB - Neurohypophyseal secretory granules have been purified from the frog (Rana esculenta) neurointermediate pituitary gland by sucrose gradient centrifugation, and their polypeptide content has been analyzed by reverse-phase high-pressure liquid chromatography. Aside from vasotocin, mesotocin, and their associated neurophysins, hydrin 2 (vasotocinyl-Gly), previously identified in hydrochloric acid extracts, has been recognized. This finding supports the previous suggestion that hydrin 2, a peptide active on the water permeability of frog bladder and frog skin, is a secreted hormone involved in osmoregulation specific to amphibians. Hydrin 2 has not been found in neurosecretory granules of birds such as the goose. PMID- 2106102 TI - Effects of a new analog of thyrotropin-releasing hormone, N alpha-[(S)-4-oxo-2 azetidinyl) carbonyl]-L-histidyl-L-prolinamide dehydrate (YM-14673) on spinal reflex potentials and flexor reflexes in spinalized rats. AB - Experiments were performed on spinalized rats, transected at the Cl level. The intravenous administration of TRH and its analog YM-14673 (N alpha-[(S)-4-oxo-2 azetidinyl) carbonyl]-L-histidyl-L-prolinamide dehydrate) produced marked increases in the amplitude of mono- and polysynaptic reflex potentials and those of the withdrawal flexor reflexes. The effects of YM-14673 were stronger and longer-lasting than those of TRH. The stimulant action of TRH and YM-14673 on the flexor reflexes was not antagonized by prazosin, chlorpromazine, haloperidol or cyproheptadine, suggesting no involvement of the release of catecholamines or serotonin in the stimulant effects of TRH and its analog. Therefore, YM-14673 may be beneficial for the treatment of several spinal motor neuron diseases. PMID- 2106103 TI - Diarrhea complicating enteral feeding after liver transplantation. AB - In this case report we present in detail the complex nature of enteral feeding, diarrhea, hypoalbuminemia, and edema in a critically ill patient. We also discuss the use of a peptide-elemental formula in this patient, who suffered continuous diarrhea for 15 weeks after liver transplantation. Use of this formula was associated with cessation of the diarrhea and permitted adequate nutritional delivery. After 26 weeks of mechanical pulmonary ventilation, extubation was possible. This case illustrates the ineffectiveness of parenteral albumin infusions for treatment of enteral edema and demonstrates the restoration of normal intestinal absorptive capacity when ultrafiltration was instituted and the patient's generalized edematous state was corrected. PMID- 2106104 TI - Maternal and infant folate status relationships. PMID- 2106105 TI - The use of quality-adjusted life years (QALYs) in the economic appraisal of health care. PMID- 2106106 TI - Listeria in food. PMID- 2106107 TI - The prevalence of autoantibodies and lupus anticoagulant in healthy pregnant women. AB - Abnormal autoantibodies have recently been implicated in pregnancy wastage. The normal autoantibody profile of pregnancy has so far, however, not been established. We investigated the effect of pregnancy on autoantibody production prospectively and longitudinally. Forty-three healthy pregnant women were compared with 50 nonpregnant healthy controls matched for age, race, and various obstetric and medical indices. All sera were tested for total immunoglobulin (Ig) levels; IgG, IgM, and IgA isotypes of autoantibodies to six phospholipids; total histone and four histone subfractions; and four polynucleotides. Plasma samples were evaluated for the presence of lupus anticoagulant. Total IgG decreased significantly in pregnant patients. The majority of autoantibody levels in pregnant women were within normal nonpregnant ranges. Only a few autoantibodies were increased in early pregnancy, including IgG antiphosphatidylinositol and H 2B, IgM antiphosphatidylinositol and phosphatidic acid, and IgA antiphosphatidylinositol and H 4. Most autoantibodies, although increased at term, were still within the normal nonpregnant range. Normalizing the data for expanded plasma volume did not significantly alter these results. Adjustment regression analysis excluded age, race, and various medical and obstetric indicators as confounding variables for autoantibody levels. The expected and observed prevalence of positive autoantibody levels in pregnant women was not significantly different from that of nonpregnant controls. None of the pregnant women demonstrated positive lupus anticoagulant. We conclude that in normal pregnancy between 16 weeks' gestation and term, autoantibody levels are largely within the normal range. Alterations occur, if at all, at the time of delivery. PMID- 2106108 TI - Biochemical and biophysical indices of follicular development in spontaneous and stimulated ovulatory cycles. AB - This study was designed to evaluate the correlation between the follicular biophysical and biochemical indicators in spontaneous (N = 11) and stimulated (N = 110) ovulatory cycles. Ovulation was induced with clomiphene citrate in 14 cycles, gonadotropin-releasing hormone (GnRH) in 12 cycles, and human menopausal gonadotropins in 84 cycles. Patients were studied daily, starting on day 10, until sonographic verification of ovulation. Each woman had serum estradiol (E2) and LH measured daily and progesterone measured only 7 days after ovulation. In addition, the ovaries were imaged transvaginally daily and the two largest follicular diameters, volumes, cross-sectional areas, and circumferences were measured in all follicles 10 mm or larger in diameter. Ultrasonographic measurements of follicles from clomiphene-stimulated cycles were significantly larger than those from spontaneous, GnRH-, and human menopausal gonadotropins stimulated cycles (P less than .05). Serum E2 and progesterone secretion in human menopausal gonadotropins- and clomiphene-stimulated cycles were significantly higher than in spontaneous and GnRH-stimulated cycles (P less than .01). Women treated with human menopausal gonadotropins developed significantly more follicles than with any other treatment (P less than .05). Correlation analysis indicated that biophysical variables alone (follicular diameter, volume, cross sectional area, or circumference) were good indicators of normal follicular development and predicted the mid-cycle LH surge in spontaneous (r = 0.81, P less than .001), GnRH- (r = 0.78, P less than .001), and clomiphene citrate-stimulated cycles (r = 0.83, P less than .001). However, in human menopausal gonadotropins stimulated cycles, both serum E2 levels and ultrasonographic evaluation were necessary to decide the best time for hCG administration (r = 0.55, P less than .001). PMID- 2106109 TI - Unsuspected leiomyosarcoma: treatment with a gonadotropin-releasing hormone analogue. AB - We present a case of a 46-year-old woman evaluated for abnormal uterine bleeding and an enlarged uterus, with normal endometrial sampling. Three months of leuprolide acetate injections resulted in a nonenlarging uterus and resolution of iron deficiency anemia and menorrhagia. Intraoperative examination suggested leiomyosarcoma, which was confirmed by postoperative permanent histologic sections. Residual uterine sarcomatous disease was confirmed on reexploration. Similar cases will continue to raise arguments against conservative hormonal intervention in the perimenopausal woman with an enlarged uterus. As the gynecologist gains familiarity with the use of gonadotropin-releasing hormone analogue therapy in the treatment of myomatous uteri, the criteria for hysterectomy will become less rigid and the potential for delay in the diagnosis and treatment of sarcomatous disease will become more common. Physicians must be cognizant of this potential complication of conservative therapy of leiomyomata uteri. PMID- 2106110 TI - Leuprolide acetate in the management of ureteral obstruction caused by endometriosis. AB - Endometriotic ureteral obstruction is a serious event commonly diagnosed late and therefore associated with a major risk of hydronephrotic renal atrophy. The standard therapy is surgical. However, medical treatment has been reported using danazol, progestins, and estrogen-progestin combinations, although solid documentation of the effect of hormonal therapy against ureteral endometriosis is lacking. Gonadotropin-releasing hormone (GnRH) agonist treatment of endometriosis has yielded good results but has not been adequately reported in patients with ureteric involvement. We report three patients treated with a GnRH agonist, leuprolide acetate, for 6-9 months as a preoperative course. One patient had bilateral and two had unilateral obstruction. The preoperative course relieved the obstruction in the patient with bilateral disease and in one with unilateral changes. The failure occurred in a patient with intrinsic ureteric endometriosis. This early experience suggests a place for GnRH agonist therapy for patients with ureteric obstruction due to endometriosis, probably, but not necessarily, in conjunction with a planned surgical procedure. If medical therapy is attempted, close surveillance of renal function is mandatory. PMID- 2106111 TI - Science is for the moment and truth is forever. PMID- 2106112 TI - Description and clinical importance of the lymphatics of the vocal fold. AB - Findings of the presence of lymphatics in the subepithelial connective tissue layer of the true vocal cord range from the statement that lymphatics are absent to the observation that a dense lymphatic network exists. This is undoubtedly a result of the different methods of examination. The entire extent of a lymphatic system can be shown by either an enzyme histochemical demonstration of the 5' nucleotidase activity in the lymphatics, or electron microscopy, which is more elaborate. These two methods are used to describe a subepithelial lymphatic network of varying density in 80 human vocal folds, which--contrary a frequent assumption--is not interrupted in the area of the free margin of the true vocal cord. Under the squamous epithelium, the density of the lymphatic system, which is very high in the arytenoid region, decreases continuously toward the anterior portion of the true vocal cord. It is exactly in the region in which the lymphatic system is the sparsest that almost all cancers of the true vocal cord develop. This finding is highly significant, in view of the low incidence of lymphogenous metastasis formation in T1-glottic cancers. PMID- 2106113 TI - Comparative study of the sensitivity of head and neck cell lines to methotrexate (MTX) and the analog 10-ethyl, 10-deazaaminopterin (10-EdAM). AB - Squamous cell lines cultured in vitro provide a potential test system for the selection of analogs that have an improved therapeutic index. The growth inhibitory effects of methotrexate and the new folate analog 10-ethyl, 10 deazaaminopterin were compared in three in vitro-cultured human head and neck squamous cell carcinoma cell lines. The inhibitory concentrations of the new analog were 10- to 100-fold lower than the inhibitory concentrations of methotrexate. The sensitivity of these three head and neck squamous cell carcinoma cell lines to both drugs was essentially the same as the sensitivity of a rhabdomyosarcoma cell line known to be very sensitive to methotrexate when the cell line is grown as a xenograft in athymic nude mice. These data indicate that 10-ethyl, 10-deazaaminopterin may be a new and effective agent against head and neck squamous cell carcinoma. PMID- 2106114 TI - Gadolinium-enhanced magnetic resonance imaging in facial nerve lesions. AB - We present our 2-year experience with a contrast enhancement agent in magnetic resonance imaging (MRI) examining facial nerve pathology. Characteristics of the agent gadolinium diethylenetriamine pentaacetic acid are reviewed. The radiographic capability to differentiate pathologic vs. normal facial nerves based on enhancement and a change in signal intensity generated by the nerve is demonstrated. Experience with facial nerve disorders including Bell's palsy, facial nerve neuromas, a facial nerve graft site, postoperative facial paralysis, and traumatic facial paralysis is presented. The ability to image the facial nerve in Bell's palsy provides an entirely new means of examining this disorder, and its implications are discussed. The ability to enhance the paralyzed facial nerve in the temporal bone after posterior fossa surgery supports a previously held concept as to the pathophysiology of this problem. PMID- 2106115 TI - The petrous carotid artery: anatomic relationships in skull base surgery. AB - Advanced transcranial lesions may be successfully resected through a variety of contemporary skull base approaches. The identification and isolation of the internal carotid artery throughout its petrous course is essential in most of these surgical techniques. Anatomic landmarks normally used to identify this vital structure, however, may be severely distorted by tumor involvement or previous operative dissection. In an effort to define surgical landmarks that may be used in the identification of the petrous carotid artery, histologic sections of 100 temporal bones from adults were examined and microscopic measurements were recorded from the anatomic dissection of 10 fresh cadaver halfheads. On the basis of these studies, structures we have found useful in identification of the vertical petrous carotid artery during lateral skull base approaches include the: base of the styloid process, bony vascular crest, basal turn of the cochlea, medial wall of the eustachian tube, and the cochleariform process. Identification of the horizontal segment can be achieved by the preliminary delineation of the middle meningeal artery, greater petrosal nerve, tensor tympani muscle, mandibular and maxillary divisions of the trigeminal nerve, and the eustachian tube. Specific anatomic relationships with associated measurements are detailed and correlated with selected, illustrative cases. PMID- 2106116 TI - NMR spectroscopy evaluation of plasma "oncolipids" in head and neck cancer. AB - The use of water-suppressed proton nuclear magnetic resonance spectroscopy of plasma as a serologic test for the detection of malignancy was first described in 1986. That report prompted the present study, which was undertaken to evaluate the efficacy of this test in differentiating patients who have head and neck malignancy from normal controls. Forty-six patients who had a biopsy-proven malignancy of the head and neck and 32 healthy individuals provided plasma for which the nuclear magnetic resonance spectrum was plotted, blind to patient diagnosis or group. The average line-width of methyl and methylene resonance was calculated. Significant differences (p less than 0.05) were found between the group with disease and the group with no disease for the methyl line-widths, using analysis of variance. In spite of this statistical difference, plotting of the values for the methyl, methylene, and average line-widths clearly demonstrated that these three oncolipid measures have no clinical use because of the tremendous overlap between the disease and nondisease groups. The findings of this study do not support the use of water-suppressed proton nuclear magnetic resonance spectroscopy as a clinically useful test for the diagnosis of head and neck malignancy. PMID- 2106117 TI - Orbital hemorrhage during ethmoid sinus surgery. AB - Orbital hemorrhage is an unusual complication of ethmoid surgery. A case of intraoperative orbital hemorrhage occurring during a medial maxillectomy and one occurring during a transethmoid sphenoidotomy are presented. The pathogenesis of this potentially serious complication is discussed. A sequential treatment algorithm is presented, consisting of medial orbitotomy, lateral canthotomy and inferior cantholysis, and inferior orbital decompression, along with concomitant medical management with mannitol, acetazolamide, and dexamethasone. PMID- 2106118 TI - Thyroid cancer: a computer-assisted review of 5287 cases. AB - Retrospective computer analysis of all reportable cases of thyroid cancer for the Rocky Mountain Cancer Data Systems between 1973 and 1983 was undertaken. Follow up data were available for periods of 5 to 10 years. All major histologic findings are reviewed with regard to distribution, prognostic factors, mortality rates, and some treatment modalities. Interesting observations determined by this study include: (1) the significantly greater mortality rates seen in patients with thyroid cancer after 50 years; (2) the lack of increased mortality rates in young patients with differentiated cancer; (3) the poorer prognosis of male patients of equivalent age to female patients in all histologic types of cancer in the first 5 years; (4) the lack of sexual difference in influencing mortality rates after the first 5 years in differentiated cancers and lack of sex as a prognostic indicator in undifferentiated cancers; (5) the excellent prognosis of patients with localized differentiated and medullary cancers and a better-than expected prognosis in the undifferentiated group; (6) the clear need for combined therapy (surgery and irradiation) in regional medullary cancer; (7) the observation that localized thyroid lymphoma had a higher mortality rate than had regional thyroid lymphoma; and (8) a significantly higher mortality rate in patients older than 79 years with differentiated cancer. PMID- 2106119 TI - Salicylate, mefenamate, meclofenamate, and quinine on cochlear potentials. AB - The perilymphatic spaces of guinea pig cochleae were perfused with artificial perilymph, with and without drug, at a rate of 2.5 microliters/minute for 10 minutes. The compound action potential of the auditory nerve, cochlear microphonics, and the summating potential evoked by 10 kHz tone bursts of varying intensities were recorded from a wire inserted in the basal turn scala vestibuli. The endocochlear potential was recorded from the scala media. Sodium salicylate (1.25 to 10 mmol/L) reduced the magnitude of the compound action potential evoked by low-sound intensities without affecting the compound action potential evoked by high-sound intensities. Sodium salicylate also reduced cochlear microphonics and had no effect on summating potential. Cochlear perfusions of prostaglandin synthesis inhibitors, mefenamate (200 mumol/L), and meclofenamate (200 mumol/L), had no effect on the cochlear potentials. Quinine (10 to 100 mumol/L) reduced the compound action potential input-output function in a parallel fashion rather than selectively affecting the low-intensity compound action potential. Quinine (100 mumol/L) reduced cochlear microphonics and summating potential. Neither quinine (100 mumol/L) nor salicylate (5 mmol/L) affected endocochlear potential. These results suggest that salicylate-induced hearing loss is not caused by either antagonism of the hair cell transmitter or cyclooxygenase inhibition, nor is it caused by the same mechanism that causes quinine-induced hearing loss. PMID- 2106120 TI - Candida myositis manifesting as a discrete neck mass. PMID- 2106121 TI - Primary malignant lymphoma of the parotid gland--two case reports. PMID- 2106122 TI - Lipoma of the middle ear: an unusual presentation in a 4-year-old child. PMID- 2106123 TI - Bilateral middle ear lobular capillary hemangiomas. PMID- 2106124 TI - Labyrinthitis ossificans following post-traumatic hearing loss and vertigo: a case report with antemortem histopathology. PMID- 2106125 TI - Diverticulum of the valleculae. PMID- 2106126 TI - Cost-effectiveness of rapid latex agglutination testing and throat culture for streptococcal pharyngitis. AB - Decision analysis was used to evaluate the cost-effectiveness of four alternative strategies for management of pharyngitis in children ("treat all," "antigen test alone," "culture alone," "antigen test + culture"). In the model, estimates of test sensitivity and specificity, disease prevalence, treatment rates after positive test results, rates of complications for treated and untreated patient cases, rates of antibiotic-induced complications, treatment effectiveness, and direct dollar costs of diagnosis and therapy were used. Results were expressed in terms of severe penicillin reactions per disease case prevented and dollars per complication prevented. Sensitivity analysis was performed to assess the impact of changes in parameter estimates on model outcomes. With treat all, 90% of streptococcal complications were prevented and there were low short-term direct dollar costs. However, treat all is associated with a high rate of penicillin allergy (70% of which occurs in uninfected children) and is the least cost effective strategy when the costs of treating complications are included. The marginal cost of antigen test + culture is less than the cost of either one-test strategy. Antigen test + culture is the most cost-effective strategy when the costs of managing the complications of streptococcal infection are considered. Antigen test + culture is the most clinically effective strategy, and its benefits are obtained at a modest marginal cost relative to the one-test strategy. PMID- 2106127 TI - Furosemide effect on mineral status of parenterally nourished premature neonates with chronic lung disease. AB - In this study, the effect of prolonged furosemide administration on calcium and phosphorus homeostasis was examined in 16 parenterally nourished very low birth weight infants with chronic lung disease. Patients received one of three different dosages of phosphorus: low, 0.91 +/- 0.06 mmol/kg per day; moderate, 1.24 +/- 0.02 mmol/kg per day; and high, 1.64 +/- 0.06 mmol/kg per day. All furosemide-treated patients had high levels of urinary calcium (12.1 +/- 2.2 mg/kg per day), phosphate (19.1 +/- 2.7 mg/kg per day), and cyclic 3'5'-adenosine monophosphate (76.8 +/- 6.7 nmol/kg per day) excretion, independent of their phosphorus intake. Parathyroid hormone concentrations were high in furosemide treated patients (0.95 +/- 0.15 ng/mL) compared with patients not treated with furosemide and receiving either moderate (0.49 +/- 0.05 ng/mL) or low (0.42 +/- 0.07 ng/mL) phosphorus intakes. Furosemide administration may lead to secondary hyperparathyroidism. PMID- 2106128 TI - Cost-effectiveness analysis in pediatric practice. PMID- 2106129 TI - [Mammographic screening for breast cancer--a cost-benefit analysis]. AB - A cost-benefit analysis of the Swedish model for screening for neoplasma malignum mammae revealed scientific shortcomings in the basis for decision. It was not possible to determine whether the screening model involved a net loss or a net profit for the individual woman. Since false confidence seems to increase the mortality in breast cancer a new dimension was introduced, a sensitivity index as an expression of revealed fractions of the incidence in the participant population. This sensitivity index estimated some two thirds of the malignant neoplasms which are normally diagnosed in a two year period. PMID- 2106130 TI - Effects of amperozide on induced turning behaviour in 6-OHDA lesioned rats. AB - The effect of amperozide on DA synapses was studied in 6-OHDA lesioned rats exhibiting a specific turning behaviour in response to the DA agonists apomorphine and pergolide or indirectly acting stimulating agents like amphetamine. Amperozide, unlike classical neuroleptics, failed to antagonize apomorphine induced turning behaviour in a regular fashion, but showed pergolide antagonism within the D2 receptor selective dose range, suggesting a type of selective interference with dopaminergic nerve transmission which differs from that caused by classical neuroleptics. Furthermore, amperozide antagonized the turning behaviour induced by amphetamine, presumably by interfering with the availability of newly synthesized DA and NA suggesting a similar influence also on other DA releasing agents. Although amperozide potentiated the effects of alpha-MPT, the drug seemed not to influence the reserpine sensitive pool of DA. PMID- 2106131 TI - Effect of amperozide on the synthesis and turnover of monoamines in rat brain. AB - The effects of amperozide on the synthesis and the turnover of monoamines in different brain regions of the rat were determined using both ex vivo and in vivo biochemical techniques (i.e. post-mortem measurements of the tissue levels by HPLC-EC, and direct measurements with the in vivo voltammetry technique). It was found that amperozide slightly increased the DOPA accumulation and the DOPAC content in limbic brain areas but not in the striatum. The DOPA accumulation was also slightly increased in the noradrenaline rich cortical region indicating increased synthesis of noradrenaline. Furthermore, amperozide increased the utilization of noradrenaline after tyrosine hydroxylase inhibition by alpha methyl-p-tyrosine. The synthesis of 5-HT was not significantly altered by amperozide. In conclusion, the biochemical data obtained in this study suggest that amperozide produces preferential effects on the mesolimbic dopaminergic system. In addition, amperozide also interacts with the noradrenergic system. PMID- 2106132 TI - Pseudomonas chromosomal replication origins: a bacterial class distinct from Escherichia coli-type origins. AB - The bacterial origins of DNA replication have been isolated from Pseudomonas aeruginosa and Pseudomonas putida. These origins comprise a second class of bacterial origins distinct from enteric-type origins: both origins function in both Pseudomonas species, and neither functions in Escherichia coli; enteric origins do not function in either pseudomonad. Both cloned sequences hybridize to chromosomal fragments that show properties expected of replication origins. These origin plasmids are highly unstable, are present at low copy number, and show mutual incompatibility properties. DNA sequence analysis shows that both origins contain several 9-base-pair (bp) E. coli DnaA protein binding sites; four of these are conserved in position and orientation, two of which resemble the R1 and R4 sites of the E. coli origin. Conserved 13-bp direct repeats adjacent to the analogous R1 site are also found. No GATC sites are in the P. aeruginosa origin and only four are in the P. putida origin; no other 4-bp sequence is present in high abundance. Both origins are found between sequences similar to the E. coli and Bacillus subtilis dnaA, dnaN, rpmH, and rnpA genes, a gene organization identical to that for B. subtilis and unlike that of E. coli. A second autonomously replicating sequence was obtained from P. aeruginosa that has some properties of bacterial origins. PMID- 2106133 TI - Subcellular distribution of small GTP binding proteins in pancreas: identification of small GTP binding proteins in the rough endoplasmic reticulum. AB - Subfractionation of a canine pancreatic homogenate was performed by several differential centrifugation steps, which gave rise to fractions with distinct marker profiles. Specific binding of guanosine 5'-[gamma-[35S]thio]triphosphate (GTP[gamma-35S]) was assayed in each fraction. Enrichment of GTP[gamma-35S] binding was greatest in the interfacial "smooth" microsomal fraction, expected to contain Golgi and other smooth vesicles. There was also marked enrichment in the rough microsomal fraction. Electron microscopy and marker protein analysis revealed the rough microsomes (RMs) to be highly purified rough endoplasmic reticulum (RER). The distribution of small (low molecular weight) GTP binding proteins was examined by a [alpha-32P]GTP blot-overlay assay. Several apparent GTP binding proteins of molecular masses 22-25 kDa were detected in various subcellular fractions. In particular, at least two such proteins were found in the Golgi-enriched and RM fractions, suggesting that these small GTP binding proteins were localized to the Golgi and RER. To more precisely localize these proteins to the RER, native RMs and RMs stripped of ribosomes by puromycin/high salt were subjected to isopycnic centrifugation. The total GTP[gamma-35S] binding, as well as the small GTP binding proteins detected by the [alpha-32P]GTP blot overlay, distributed into fractions of high sucrose density, as did the RER marker ribophorin I. Consistent with a RER localization, when the RMs were stripped of ribosomes and subjected to isopycnic centrifugation, the total GTP[gamma-35S] binding and the small GTP binding proteins detected in the blot overlay assay shifted to fractions of lighter sucrose density along with the RER marker. PMID- 2106134 TI - A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome. AB - A small proteoglycan that contains only a single dermatan sulfate chain is the main proteoglycan synthesized by skin fibroblasts. Fibroblasts from a patient with progeroidal appearance and symptoms of the Ehlers-Danlos syndrome have a reduced ability of converting the core protein of this proteoglycan into a mature glycosaminoglycan chain-bearing species. This abnormality is the consequence of a deficiency in galactosyltransferase I (xylosylprotein 4-beta galactosyltransferase; EC 2.4.1.133), which catalyzes the second glycosyl transfer reaction in the assembly of the dermatan sulfate chain. The glycosaminoglycan-free core protein secreted by the patient's fibroblasts bears an unsubstituted xylose residue. The mutant enzyme is abnormally thermolabile. Preincubation of fibroblasts at 41 degrees C leads to a further reduction in the production of mature proteoglycan and affects the capacity for glycosaminoglycan synthesis on p-nitrophenyl beta-D-xyloside more strongly in the mutant than in control cells. PMID- 2106135 TI - Cross-linking Fc receptors stimulate splenic non-B, non-T cells to secrete interleukin 4 and other lymphokines. AB - Spleen cell populations depleted of both B and T lymphocytes produce interleukin 4 (IL-4) in response to stimulation with immunoglobulins bound to the surface of culture dishes. In the presence of interleukin 3 (IL-3), plate-bound (PB) IgE and PB-IgG1, IgG2a, and IgG2b are excellent stimulants, whereas PB-IgA and PB-IgM fail to stimulate IL-4 production. In the absence of IL-3, PB-IgE stimulates relatively modest production of IL-4, whereas PB-IgG2a generally does not. The response to PB-IgE is inhibited by soluble IgE; antibody to Fc gamma receptor II inhibits the response to PB-IgG2a. Thus, separate receptors mediate these stimulations, and Fc receptor cross-linkage is required for IL-4 production. Depletion of cells expressing asialo-GM1 does not diminish IL-4 production in response to PB immunoglobulins, indicating that natural killer cells are not essential for non-B, non-T cell production of IL-4. In addition to IL-4, non-B, non-T cells produce IL-3, but no detectable interleukin 2 or interferon gamma. Non-B, non-T cells may be an important source of lymphokines in a variety of immune responses and may serve to amplify the effects of T cells of the TH2 type. PMID- 2106136 TI - Relationship between protein synthesis and concentrations of charged and uncharged tRNATrp in Escherichia coli. AB - We have continuously monitored Trp-tRNA(Trp) concentrations in vivo and, in the same cultures, measured rates of protein synthesis in isogenic stringent and relaxed strains. We have also manipulated cellular charged and uncharged [tRNA(Trp)] by two means: (i) the strain used contains a Trp-tRNA synthetase mutation that increases the Km for Trp; thus, varying exogenous Trp varies cellular Trp-tRNA(Trp); and (ii) we have introduced into the mutant strain a plasmid containing the tRNA(Trp) gene behind an inducible promoter; thus, total [tRNA(Trp)] also can be varied depending on length of induction. The use of these conditions, combined with a previously characterized assay system, has allowed us to demonstrate that (i) the rate of incorporation of Trp into protein is proportional to the fraction of tRNA(Trp) that is charged; for any given total [tRNA(Trp)], this rate is also proportional to the [Trp-tRNA(Trp)]; (ii) uncharged tRNA(Trp) inhibits incorporation of Trp into protein; and (iii) rates of incorporation into protein of at least two other amino acids, Lys and Cys, are also sensitive to [Trp-tRNA(Trp)] and are inhibited by uncharged tRNA(Trp). Our results are consistent with models of translational control that postulate modulating polypeptide chain elongation efficiency by varying concentrations of specific tRNAs. PMID- 2106139 TI - Corticosteroid regulation of gonadotropin secretion and induction of ovulation in the rat. AB - In the human polycystic ovarian syndrome, glucocorticoids have been demonstrated to have beneficial effects in inducing ovulation in a number of cases. These beneficial effects were assumed to be due to suppression of adrenal overproduction of androgens. However, the possibility exists that glucocorticoids may directly regulate gonadotropin secretion and thereby improve menstrual rhythm and ovulatory activity. Herein, we report that the corticoid, deoxycorticosterone, and the synthetic glucocorticoid, triamcinolone acetonide, like progesterone (P4), are able to induce luteinizing hormone and follicle stimulating hormone surges and facilitate ovulation in the pregnant mare serum gonadotropin-primed rat. This effect is not shared by cortisol. Prolactin release was also stimulated by deoxycorticosterone, cortisol, and progesterone, but not by triamcinolone acetonide. Similar to progesterone, triamcinolone acetonide and deoxycorticosterone administration caused a loss of fluid retention in the uterus. This effect of triamcinolone acetonide and deoxycorticosterone may be related to progesterone action as opposed to anti-inflammatory action since cortisol had no effect on uterine fluid retention. These findings raise the possibility that the beneficial effects seen with glucocorticoids in inducing ovulation in polycystic ovarian syndrome may be due in part to their direct effects upon the release of gonadotropins. PMID- 2106138 TI - Transforming growth factor beta decreases the immunogenicity of rat islet xenografts (rat to mouse) and prevents rejection in association with treatment of the recipient with a monoclonal antibody to interferon gamma. AB - Culture of rat islets of Langerhans for 1 week at 37 degrees C with recombinant transforming growth factor beta prolonged the survival of islet xenografts transplanted into diabetic mouse recipients. Treatment of diabetic recipients with a neutralizing monoclonal antibody to murine interferon gamma did not affect the survival of islet xenografts cultured 7 days in control medium. However, treatment of donor islets with transforming growth factor beta in combination with treatment of diabetic recipients with interferon gamma antibody produced a 75% survival of the islet xenografts at 100 days. Fifty percent of the recipients who had accepted their graft for more than 100 days were immune unresponsive to a transplant of freshly isolated islets from the same donor strain. PMID- 2106137 TI - Structure and expression of murine germ-line immunoglobulin epsilon heavy chain transcripts induced by interleukin 4. AB - The murine lymphokine, interleukin 4 (IL-4) is able to specifically promote isotype switching to IgG1 and IgE in cultures of mitogen-stimulated B cells. Emerging evidence suggests that germ-line immunoglobulin heavy chain gene transcription may direct switching by modulating switch-region accessibility to a recombinase. In this study, cloned cDNA copies of the germ-line epsilon heavy chain transcript have been used to determine the genomic organization of this transcription unit. The 5' end of these transcripts are derived from an exon, denoted I epsilon, located 2 kilobases 5' of the C epsilon switch region [C epsilon = epsilon heavy chain constant (C) region gene]. Nucleotide sequence analysis reveals that this RNA does not encode a protein, as the I epsilon exon contains termination codons in all reading frames. Germ-line epsilon chain transcripts can be detected in cultures of normal splenic B cells treated with IL 4 within 24 hr, and this expression correlates with subsequent switching to C epsilon. Consistent with the IL-4 inducibility of this RNA is the identification of a motif upstream from the site of transcription initiation that closely resembles a transcription element implicated in the IL-4 regulation of the gene encoding the murine class II histocompatibility antigen, A alpha k. These data lend support to the accessibility model of isotype switching and implicate IL-4 in the transcriptional activation of the C epsilon locus. PMID- 2106140 TI - Hyposmolar stimulation of secretion of thyrotropin, prolactin, and luteinizing hormone does not require extracellular calcium and is not inhibited by colchicine, cytochalasin B, ouabain, or tetrodotoxin. AB - Hyposmolar stimulation of thyroid-stimulating hormone, prolactin, and luteinizing hormone secretion by dispersed perifused rat pituitary cells was not depressed by removal of Ca2+ from the perifusion medium or by 0.1 mM colchicine, 20 microM cytochalasin B, 0.1 mM ouabain, or 3 microM tetrodotoxin. The secretory response induced by medium hyposmolarity or by thyrotropin-releasing hormone was not appreciably different at 23, 37, or 43 degrees C, but was markedly reduced or abolished when the experiments were performed at 1 degree C. These data indicate that microtubules or microfilaments, transport of extracellular Ca2+ into the cytoplasm, and plasmalemma ion transport mechanisms sensitive to ouabain or tetrodotoxin are not essential components of the mechanism by which extracellular hyposmolarity induces secretion. PMID- 2106141 TI - Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone. AB - It has been shown that mice transgenic for human growth hormone-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs and mammosomatotrophs, cells capable of producing both growth hormone and prolactin, by 8 months of age. We now report for the first time that old GRH-transgenic mice, 16 to 24 months of age, develop pituitary mammosomatotroph adenomas. These findings provide conclusive evidence that protracted stimulation of secretory activity can cause proliferation, hyperplasia and adenoma of adenohypophysial cells. PMID- 2106142 TI - A comparison of the efficacy and safety of buserelin vs danazol in the treatment of endometriosis. Protocol 310 Study Group. PMID- 2106143 TI - Electrosurgery: advantages and disadvantages. AB - Though electrosurgery has been with us for decades, few surgeons have received formal training in its potential uses. The erroneous belief that electrosurgery techniques increase scar formation or impair healing processes, has led surgeons to other methods to deliver energy to the living cell. A watt, is a watt, is a watt--knowing how to calculate and administer that energy is the challenge. Fig. 4. Laser technology has forced the bioelectrical engineers to develop improved electrogenerators and accessories that are easier to understand and control. The use of digital reader boards, displayed in watts rather than an arbitrary dial setting is one example. A current flow meter for bipolar forceps will now tell the surgeon when all of the tissue has been desiccated. Soon I hope the power density and wattage delivered at the electrode tip will be easily displayed for the gynecologic surgeons. Who knows, one day we may have a "laser-electrode" system to meet all of our needs. PMID- 2106144 TI - In vitro fertilization and embryo transfer: an established and successful therapy for endometriosis. PMID- 2106145 TI - Leuprolide acetate for the treatment of endometriosis. PMID- 2106146 TI - Efficacy and safety of intranasal buserelin acetate in the treatment of endometriosis: a review of six clinical trials and comparison with danazol. AB - The efficacy and safety of buserelin acetate in the treatment of endometriosis was studied in 4 open non-comparative trials and 2 open randomized comparative trials with danazol. 444 women were enrolled in the buserelin group and 89 in the danazol group. Treatment was for 6-10 months using 900-1200/micrograms intranasal buserelin/day and 400-800/micrograms oral danazol/day; patients were followed up for 6-8 months. Endometriotic lesions improved or disappeared in most women; pain (dysmenorrhoea, dyspareunia and pelvic pain) subsided rapidly. Most women had no, or alleviated, symptoms throughout follow-up, although ovarian function resumed promptly. Nearly a quarter of infertile women with a desire for children became pregnant. No significant differences between treatments emerged. Buserelin treatment was characterized by menopausal-like symptoms in most women, as well as by headache and nausea. Danazol treatment, which also gave rise to these effects, was accompanied by weight gain, myalgia and acne in a considerable proportion of women, as well as other anabolic and androgenic side effects. Buserelin would thus appear to be a safe and effective alternative to the standard therapy, danazol, in the treatment of endometriosis. PMID- 2106147 TI - Evaluation of preoperative use of danazol, gestrinone, lynestrenol, buserelin spray and buserelin implant, in the treatment of endometriosis associated infertility. PMID- 2106148 TI - The effects of nigrostriatal 6-hydroxydopamine lesions on dopamine D2 receptor mRNA and opioid systems. PMID- 2106149 TI - Chronic morphine administration and in vivo pertussis toxin treatment induce hyperalgesia and enhance 3H-nitrendipine binding. PMID- 2106150 TI - Ritanserin, a 5-HT2 receptor antagonist, does not modify ECT-induced prolactin release. AB - The effect of pretreatment with ritanserin, a potent and selective serotonin-S2 (5-HT2) receptor antagonist, on the prolactin (PRL) response to electroconvulsive therapy (ECT) was studied in seven female patients suffering from major depressive disorder. They were given either ECT alone, or ECT after 10 or 20 mg ritanserin PO, and PRL was estimated in blood samples taken at times -5, 0, +5, +15, +30 and +60 min. The PRL responses after drug administration were not different from the responses after ECT alone. We conclude that, if serotonergic mechanisms are involved in the ECT-induced PRL increase, this neuroendocrine response seems to be rather a 5-HT1 than 5-HT2 receptor mediated event. PMID- 2106152 TI - The role of the frontal eye field and its corticotectal projection in the generation of eye movements. PMID- 2106151 TI - [High frequency long-term analysis and psychoanalytic practice. Utopia and reality]. AB - On the basis of the prognostic study of psychotherapeutic treatment in the Federal Republic and of the evaluation of more than 1000 applications for insurance benefits submitted in the years from 1973 to 1983, it is suggested that high-frequency long-term analysis is the exception rather than the rule and that it is carried on almost exclusively by a small group of "privileged" therapists. The author asks what this implies for the definition of psychoanalysis and for daily treatment practice. Are therapists being trained for a kind of treatment that they will rarely or never practice? The author urges resumption of the discussion of theory and technique of psychoanalysis in which these questions will be considered. PMID- 2106153 TI - Contribution of the nucleus of the optic tract to optokinetic nystagmus and optokinetic afternystagmus in the monkey: clinical implications. AB - 1. The role of the pretectal NOT and the DTN in producing horizontal OKN and OKAN were studied using electrical stimulation and lesions. Positive stimulation sites lay in NOT, DTN, and in a fiber bundle in the pulvinar that is presumably a cortical input to NOT. 2. When the region of NOT was electrically stimulated in darkness, horizontal nystagmus was evoked with ipsilateral slow phases. Eye velocity rose slowly to a steady-state level and was followed by afternystagmus at the end of stimulation. The time constant of rise of stimulus-induced nystagmus was similar to the slow rise of slow-phase eye velocity during OKN. The saturation velocity of the induced nystagmus and the falling time constant of the stimulus afternystagmus were the same as those of OKAN. This suggests that electrical stimulation of NOT and DTN had elicited the slow component of OKN, i.e., that component produced by the velocity storage mechanism in the vestibular system. 3. Consistent with this postulate, activity induced by NOT stimulation could enhance, prolong, or block the slow component of OKN and OKAN depending on whether slow phases were to the same or opposite side. Stimulus-induced activity also interacted with vestibular nystagmus as would OKN and OKAN. 4. Unilateral lesions of NOT and DTN caused a loss of OKAN and the slow rise in OKN to the ipsilateral side. Steady-state velocities of OKN were reduced. The initial jump of OKN slow-phase velocity was the same or somewhat less after lesions but was not lost. 5. Partial lesions of a fiber bundle in the lateral pulvinar caused a transient change in OKN and OKAN, consistent with the idea that it carries activity for the slow component from the cortex to NOT. A lesion of the MRF, just rostral to the superior colliculus, caused a transient loss of the rapid component of OKN. This region appears to carry activity responsible for the initial jump in slow-phase velocity at the onset of stimulation. 6. We conclude that: (a) NOT and probably DTN lie in the indirect pathway that produces the slow component of horizontal OKN and OKAN to the ipsilateral side in the rhesus monkey. This pathway activates the velocity storage mechanism in the vestibular nuclei. (b) At the level of NOT, the pathway responsible for the slow component of OKN and OKAN is anatomically distinct from the pathway responsible for rapid changes in eye velocity at the onset of OKN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2106154 TI - The visual system in Parkinson's disease. PMID- 2106155 TI - The on and off channels of the visual system. PMID- 2106156 TI - [Skin spots, skin nodules, gangrene of the toes]. AB - A 42-year-old man with multiple cutaneous neurofibromacules, cafe-au-lait and gangrene of toes was diagnosed having neurofibromatosis in 1976. An aortography performed because of severe hypertension had shown a coarctation and bilateral renal artery stenosis in 1982. Conservative antihypertensive therapy with an ACE inhibitor, a vasodilatating agent and a diuretic resulted in gradual normalisation of blood pressure values. A recent follow-up revealed minimal progression of neurofibromatosis and hypertensive lesions documenting a benign course for over 13 years. PMID- 2106157 TI - [Classification and definition of epileptic syndromes]. AB - Epileptic syndromes are classified in order to supply the clinician with a useful terminology. A description of individual types of seizure is not relevant in practice since identical seizures occur in patients with very different outcomes. An epileptic syndrome is an epileptic disorder characterized by a cluster of signs and symptoms. It has therapeutic and prognostic implications. Our proposal for classification of epileptic syndromes is a compromise between scientific classification and practical arrangement. PMID- 2106158 TI - [Hepatitis C virus (HCV), anti-HCV and non-A, non-B hepatitis]. AB - Our data on 559 serum samples are discussed in the light of the present knowledge on hepatitis C virus (HCV). This newly discovered virus is thought to be the main cause of the bloodborne non-A, non-B hepatitis. HCV is a single-stranded, encapsulated RNS virus. Presently one antibody, anti-HCV, is detectable, which is directed against a nonstructural viral component. This antibody appears only weeks to months after infection or onset of the disease. Within 6-9 months 60-80% of the patients with resolving non-A, non-B hepatitis become positive, with the anti-HCV usually disappearing after 1-5 years. Patients with chronic infections are positive in 70-90% of cases, with the antibody usually persisting over decades. The presence of anti-HCV offers no clue as to whether there is an ongoing or past infection and does not serve to judge infectivity or immunity. 0.34% of the blood donors in Switzerland are anti-HCV positive, with 1.3% in Southern Italy and 0.6-0.8% in Northern Italy, Great Britain, France and Germany. Anti-HCV prevalence is high in hemophiliacs (59-97%), i.v. drug users (48-92%) hemodialysis patients and polytransfused individuals (3-23%), homosexuals and promiscuous heterosexuals (1-40%) as well as in patients with non-B hepatoma (62 80%) or with alcoholic cirrhosis (27-52%). Our own data show anti-HCV in 45% of i.v. drug users, 7% of homosexuals, 13% of patients under hemodialysis or with renal transplants, and in 60% of patients with chronic non-A, non-B hepatitis. PMID- 2106159 TI - Activin-binding protein from rat ovary is follistatin. AB - Activin, a member of the transforming growth factor beta protein family, was originally isolated from gonadal fluids and stimulates the release of pituitary follicle-stimulating hormone (FSH). Activin has numerous functions in both normal and neoplastic cells. Various cells synthesize activin and have a specific binding site for this peptide. However, the molecular basis for its actions is unknown. A binding protein for activin was purified from rat ovary and was identical to follistatin, a specific inhibitor of FSH release. It is likely that the binding protein participates in the diverse regulatory actions of activin. PMID- 2106160 TI - Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation. AB - The nucleosome is the fundamental unit of assembly of the chromosome and reversible modifications of the histones have been suggested to be important in many aspects of nucleosome function. The structure-function relations of the amino-terminal domain of yeast histone H4 were examined by the creation of directed point mutations. The four lysines subject to reversible acetylation were essential for histone function as the substitution of arginine or asparagine at these four positions was lethal. No single lysine residue was completely essential since arginine substitutions at each position were viable, although several of these mutants were slower in completing DNA replication. The simultaneous substitution of glutamine for the four lysine residues was viable but conferred several phenotypes including mating sterility, slow progression through the G2/M period of the division cycle, and temperature-sensitive growth, as well as a prolonged period of DNA replication. These results provide genetic proof for the roles of the H4 amino-terminal domain lysines in gene expression, replication, and nuclear division. PMID- 2106161 TI - Novel fluorogenic substrates for assaying retroviral proteases by resonance energy transfer. AB - The 11-kD protease (PR) encoded by the human immunodeficiency virus 1 (HIV-1) is essential for the correct processing of viral polyproteins and the maturation of infectious virus, and is therefore a target for the design of selective acquired immunodeficiency syndrome (AIDS) therapeutics. To facilitate the identification of novel inhibitors of HIV-1 PR, as well as to permit detailed studies on the enzymology and inhibition of this enzyme, a continuous assay for its activity was developed that was based on intramolecular fluorescence resonance energy transfer (RET). The assay used the quenched fluorogenic substrate 4-(4 dimethylaminophenylazo)benzoic acid (DABCYL)--Ser Gln Asn Tyr Pro Ile Val Gln--5 [(2-aminoethyl)amino]naphthalene-1 sulfonic acid (EDANS), whose peptide sequence is derived from a natural processing site for HIV-1 PR. Incubation of recombinant HIV-1 PR with the fluorogenic substrate resulted in specific cleavage at the Tyr Pro bond and a time-dependent increase in fluorescence intensity that was linearly related to the extent of substrate hydrolysis. An internally quenched fluorogenic substrate was also designed that was selectively cleaved by the related PR from avian myeloblastosis virus (AMV). The fluorescence quantum yields of the HIV-1 PR and AMV PR substrates in the RET assay increased by 40.0- and 34.4-fold, respectively, per mole of substrate cleaved. Because of its simplicity, rapidity, and precision in the determination of reaction rates required for kinetic analysis, this method offers many advantages over the commonly used high-performance liquid chromatography- or electrophoresis-based assays for peptide substrate hydrolysis by retroviral PRs. PMID- 2106162 TI - Dana-Farber Cancer Institute studies in advanced sarcoma. AB - In a phase II trial of ifosfamide 2 g/m2 days 1 to 4 with mesna uroprotection in 124 patients who had previously failed treatment for sarcomas, 3% achieved a complete response (CR), and 18% had a CR or partial response (PR). In the subset of patients with soft-tissue sarcomas, the response rate for the 64 patients who received bolus administration was 26% compared with 9% for the 60 patients who received a continuous infusion (Cl) schedule (P = .03). When mesna was unavailable, the incidence of hematuria was significant in patients, with three of four patients affected. Microscopic hematuria was uncommon in patients receiving mesna. Hematuria in the group as a whole was not associated with prior treatment with cyclophosphamide, pelvic radiotherapy, age, or a bolus versus Cl schedule. Thus, this and other studies confirm that ifosfamide is active in failed sarcomas. In sequential phase I/II trials, 111 patients who were previously untreated for metastatic or inoperable sarcomas received doxorubicin, ifosfamide, dacarbazine at doses of 60, 7,500, and 900 mg/m2, respectively, by Cl over 72 hours; myelosuppression was dose-limiting. Eleven patients (10%) achieved CRs, with an overall response rate of 47%. Most responses (approximately 70%) were observed within two cycles, and median times to progression were 10 and 9 months for CR and PR, respectively. Following CR, two patients remained disease free at 32 and 16 months. Of 15 additional patients rendered disease-free with surgery following at least a minor response to chemotherapy, two remained disease free at 30 and 18 months with no further therapy. Central nervous system (CNS) metastases developed in 11 patients, all of whom had high-grade sarcomas; seven of these patients were still responding systemically (three CRs). This regimen is undergoing evaluation in a randomized trial versus doxorubicin and dacarbazine alone in untreated advanced sarcoma and is being compared with observation in the adjuvant treatment of high-grade sarcomas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2106163 TI - Symposium on bone marrow transplantation. September 9, 1989, Dallas, TX. Proceedings. PMID- 2106164 TI - Preclinical studies relating to the use of thiotepa in the high-dose setting alone and in combination. AB - In vitro and in vivo studies with N,N',N''-triethylene-thiophosphoramide (thiotepa) alone and in combination with cyclophosphamide (CTX) were carried out using the MCF-7 human breast carcinoma cell line and the EMT6 mouse mammary carcinoma cell line. In vitro, survival curves were essentially linear. The cytotoxicity of thiotepa toward MCF-7 cells was markedly dependent on the presence of oxygen during the period of drug exposure, with a 3-log greater cell kill at 500 mumol with cells that were normally oxygenated compared with hypoxic cells. Incubation of thiotepa with an Aroclor 1254-induced rat liver S-9 homogenate in the presence of a reduced nicotinamide adenine dinucleotide phosphate-regenerating system resulted in an eightfold increase in cytotoxicity toward the MCF-7 cells over a wide range of drug concentrations. The thiotepa metabolite N,N',N''-triethylenephosphoramide (TEPA) was significantly less cytotoxic toward the MCF-7 cells than was thiotepa. Simultaneous and immediately sequential treatments with thiotepa and CTX produced supra-additive cell killing of both cell lines, although the magnitude of the supra-additivity was greater in the MCF-7 cell line than in the EMT6 cell line. These drugs Vppeared to be equally effective as thiol-depleting agents. By DNA alkaline elution, there was a pattern of increasing DNA cross-linking similar to the increasing levels of cytotoxicity of this drug combination as the concentrations of thiotepa increased. In the EMT6 tumor in vivo, the maximally tolerated combination therapy (5 mg/kg x 6, thiotepa, and 100 mg/kg x 3, CTX) produced about 25 days of tumor growth delay, which was not significantly different than expected for additivity of the individual drugs. The survival of EMT6 tumor cells after treatment of the animals with the various single doses of thiotepa and CTX was assayed. Tumor cell killing by thiotepa produced a very steep, linear survival curve through 5 logs with increasing dose. The tumor cell survival cure for CTX to 500 mg/kg had linear tumor cell kill through almost 4 logs. In vivo modeling of quasicontinuous exposure (3 intraperitoneal over 9 hours) versus pulse (single-dose) administration of thiotepa and CTX compared EMT6 tumor cell survival with survival of bone marrow as a representative sensitive normal tissue. With CTX, there was a considerable increase in the therapeutic index (killing of tumor cells/killing of colony forming units-granulocyte macrophage) when the same total dose of drug was administered in multiple injections versus a single injection. For thiotepa, smaller increases in therapeutic index were also observed with the multiple-injection schedule.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2106165 TI - High-dose N,N',N"-triethylenethiophosphoramide (thiotepa) with autologous bone marrow transplantation: phase I studies. AB - N,N',N''-triethylenethiophosphoramide (thiotepa) is a polyfunctional alkylating agent similar in structure to nitrogen mustard. Thiotepa (synthesized by American Cyanamid Company, Wayne, NJ) underwent clinical trials in the 1960s that showed that it was active against a wide variety of tumors. At a standard dose level (10 to 30 mg/m2), the dose-limiting toxicity is myelosuppression; other toxicities are infrequent. Therefore, high-dose phase I evaluation was encouraged by these observations. Approximately 217 patients have been treated with single-agent high dose thiotepa administered intravenously daily over 2 hours for 3 days followed by hematopoietic stem cell rescue to prevent prolonged myelotoxicity. The total doses administered ranged from 135 to 1,575 mg/m2. As anticipated, myelotoxicity was substantial, with 180 mg/m2 being the highest dose not requiring stem cell rescue to ensure hematopoietic recovery. Extramedullary toxicities consisted of stomatitis, dermatitis, hepatoxicity, and central nervous system (CNS) toxicity. CNS toxicity was dose-limiting; other toxicities were problematic, ie, dose dependent but not truly dose-limiting. The maximal tolerated dose of thiotepa is 900 to 1,125 mg/m2, with the lower dose being the maximal dose for evaluation in combination chemotherapy. In high-dose phase I evaluation, the overall response rate was approximately 50% with responses seen in a wide variety of solid tumors, lymphomas, and pediatric tumors. High-dose thiotepa appears to be an alkylating agent with broad-spectrum antitumor efficacy, which should add to the cytoreductive regimens for both solid and hematopoietic tumors. PMID- 2106166 TI - High-dose thiotepa alone and in combination regimens with bone marrow support. AB - Curative treatment regimens for leukemias, lymphomas, and testicular cancer have been based on laboratory observations of a clear relationship (generally linear log) between increasing doses of chemotherapeutic agents and tumor cytotoxicity and on recognition of the need for combination chemotherapy to avoid the emergence of drug resistance. Chemotherapeutic agents have been selected for combinations based on cytotoxic activity, different mechanisms of action (to avoid cross-resistance), and different dose-limiting toxicities (to avoid additive toxicity). The ideal combinations use the highest tolerable doses of active non-cross-resistant agents to minimize the potential for drug resistance and achieve optimum cytotoxicity. Dose escalation is often limited by myelosuppression. Hematologic stem cell support from bone marrow or peripheral blood allows the administration of significantly higher doses of chemotherapy. In 1977, Thomas and colleagues in Seattle reported that 13 of 100 patients who underwent bone marrow transplantation for relapsed acute leukemia were disease free 1 to 4.5 years later. Today, almost 50% of selected patients with acute myelogenous leukemia who undergo transplantation with human leukocyte antigen matched sibling donor marrow during first remission are cured. Between 20% and 50% of lymphoma patients who undergo transplantation after failing conventional treatment have survived; those whose disease is responding to standard-dose therapy at the time of transplant have the best prognosis. Conditioning regimens that are sufficiently cytoreductive are not currently available for patients with solid tumors. The diversity of solid tumors makes it likely that a variety of regimens will be required. In a sequence of laboratory and clinical studies, we have constructed and evaluated a regimen comprising 6 g/m2 of cyclophosphamide, 500 mg/m2 of N,N',N''-triethylenethiophosphoramide (thiotepa), and 800 mg/m2 of carboplatin. The response rate in women with measurable breast cancer was 81%. While profound myelosuppression was noted, organ toxicity has been rare. This regimen, designed to exploit the principles of curative cancer chemotherapy, is associated with low morbidity and high cytoreductive efficacy. The regimen is currently being evaluated in a phase II trial in patients with previously untreated metastatic breast cancer who are responsive to conventional-dose chemotherapy. Of 29 patients entered in the study, only one has died of toxicity, confirming the low incidence of treatment-related toxicity associated with the regimen. PMID- 2106167 TI - Cellular transport and accumulation of thiotepa. AB - Because the transport and accumulation of N,N',N''-triethylenethiophosphoramide (thiotepa) by cells has not been characterized, these processes were investigated with [14C]thiotepa and cultured L1210 or freshly obtained human or avian RBCs. The octanol: phosphate-buffered saline (PBS) partition coefficient of thiotepa was 2.4 +/- 0.1 (n = 8). With this value, the permeability coefficient (Ps) for thiotepa was estimated to be between 2.8 x 10(-4) and 1.81 x 10(-3) cm/sec, and the half-life of accumulation of thiotepa by L1210 cells was estimated to be 0.063 to 0.40 seconds. Thiotepa accumulation by cells was measured after incubation of cells with [14C]thiotepa and subsequent harvesting of cells by centrifugation through silicone fluid. Thiotepa accumulation by L1210 cells was biphasic. The initial phase was rapid and essentially complete by 10 seconds. The amount of cell-associated 14C increased linearly with increasing extracellular concentrations of thiotepa or with increasing size of the cell pellet. The absolute amount of cell-associated 14C was consistent with that expected if the [14C]thiotepa had been evenly distributed in the incubation medium and a volume equal to that of the cell pellet had been sampled and counted. This rapid phase of thiotepa accumulation was not slowed when cells were incubated on ice. The second phase of [14C]thiotepa accumulation occurred at a rate much slower than that of the initial phase. This slower phase of drug accumulation was linear for at least 5 hours. The rate of 14C accumulation increased progressively over a range of extracellular thiotepa concentrations from 5 to 100 nmol/mL and could not be saturated under acceptable tissue culture conditions. The slower rate of 14C accumulation was ablated by incubating cells on ice and was reduced by 30% to 50% in the presence of 1mM of sodium azide or 2,4-dinitrophenol. The slow rate of accumulation of 14C reflected summation of a relatively stable or constant amount of exchangeable 14C and an amount of nonexchangeable 14C that increased linearly from almost undetectable levels at the start of the experiment to amounts equal to 64 +/- 11% of total cellular radioactivity after 5 hours. The initial association of [14C]thiotepa with both human and avian RBCs was also very rapid. Avian RBCs also exhibited a slow rate of 14C accumulation that was linear for at least 5 hours but that was 15% to 20% that of L1210 cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2106168 TI - An analysis of psychiatric patient attributes in Salford using categorical data models. AB - Much geographical work about mental illness has been aggregative in nature and, consequently, has ignored variation that might be attributed to individuals. The research reported here is intended to reverse this trend by applying the methods of categorical data analysis to the detailed patient histories contained in the Salford Psychiatric Case Register. The paper begins by reviewing the changing prevalence rates for various diagnoses and types of care in Salford between 1968 and 1986. In the light of this background log-linear data models are fitted to evaluate relationships between service usage and patient age, diagnosis and marital status and residential location at two survey points within the study period. Significant relationships are examined in terms of their temporal stability (such as the diagnosis of schizophrenia and a marital status of single) and instability (the changing role of the community psychiatric nurse) to isolate the main combinations of categories to influence the uptake of psychiatric services. PMID- 2106169 TI - Hyperosmolar nonketotic hyperglycemia manifested as ascending polyneuropathy. AB - We have described a case of hyperosmolar nonketotic hyperglycemia atypically manifested as an ascending progressive predominantly motor neuropathy with sensory involvement. Although the patient noticed polydipsia, the lack of endogenous renal function prevented the expected polyuria and dehydration. Treatment with insulin produced such marked clinical improvement that 15 days after admission he was discharged home, fully mobile and self-sufficient. Because hyperosmolar nonketotic decompensation is uncommon and patients may initially have neurologic signs without a previous history of diabetes mellitus, the diagnosis may be overlooked. PMID- 2106170 TI - Fetal intestinal obstruction: necessity for percutaneous umbilical blood sampling to assess the severity of Rh sensitization. AB - Investigation into the severity of hemolytic disease due to Rh isoimmunization may be complicated by concurrent amniotic fluid contamination with bile. We have presented a case in which a prenatal sonogram showed evidence of fetal intestinal obstruction, which was subsequently confirmed postpartum by exploratory laparotomy. Since intrauterine regurgitation of bile occurs with intestinal obstruction distal to the papilla of Vater, percutaneous umbilical blood sampling is necessary to discern the presence and severity of hemolytic disease as indicated by an abnormal spectrophotometric absorption pattern. PMID- 2106172 TI - Islet isolation and transplantation techniques in the primate. AB - Aspects of islet transplantation in the primate have been investigated using a model of autotransplantation of islets in the monkey after total pancreatectomy. The results showed that the subcapsule of the kidney was not a good site for implantation of relatively impure islet preparations, or of purified islet preparations if the mass of tissue implanted was marginal. The spleen was a much better site for the islet implantation, allowing fasting normoglycemia in many of the animals. The results of histologic examination of the spleen four to six weeks after intrasplenic islet transplantation showed good preservation of islet morphologic features, with numerous islets scattered throughout the spleen. Cells secreting insulin, glucagon and somatostatin were present in approximately normal proportions. Transplantation of islets into the portal vein produced good short and long term function. A number of grafts failed between four and 18 months, this failure being related to the function demonstrated at six weeks by intravenous glucose tolerance tests. Animals with poor initial function tended to fail early. However, those with good initial function continued to gain weight and remain normoglycemic up to 2.5 years, providing encouragement to improve further the yield and purity of the islet preparation as well as seeking more efficient techniques for islet implantation. PMID- 2106171 TI - Serologic evidence for the role of Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis in the etiology of tubal factor infertility and ectopic pregnancy. AB - The authors used enzyme immunoassay to determine the prevalence of serum antibodies to the sexually transmitted disease (STD) organisms Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis among 104 infertile women undergoing in vitro fertilization. Altogether, 55 (72%) out of 76 women with tubal abnormalities tested positive for one or more STD organisms, compared with only 6 (21%) out of 28 infertile women with normal tubes (P less than .001). The authors obtained positive test results for C. trachomatis, N. gonorrhoeae, and M. hominis in 40%, 14%, and 37% of the patients with tubal abnormalities, respectively; of women without tubal abnormalities, the test results were 7%, 0%, and 14%, respectively. Out of 20 patients with a history of ectopic pregnancy, the authors obtained positive findings for C. trachomatis, N. gonorrhoeae, and M. hominis in 8 (40%), 1 (5%), and 7 (35%), respectively. These results indicate an independent role for all three STD organisms in the etiology of tubal factor infertility and ectopic pregnancy following both symptomatic and asymptomatic pelvic inflammatory disease (PID). The correlation between positive mycoplasmal serology and secondary infertility and tubal abnormalities may suggest a link between M. hominis infections during pregnancy and delivery complications and consequent development of tubal factor infertility. PMID- 2106173 TI - Trends in medical care costs: a look at the 1990s. PMID- 2106174 TI - Prenatal exposure to a low-frequency electromagnetic field demasculinizes adult scent marking behavior and increases accessory sex organ weights in rats. AB - Pregnant Sprague-Dawley dams were exposed to a low-level, low-frequency pulsed electromagnetic (EM) field (15 Hz, 0.3 msec duration, peak intensity 8 gauss) for 15 min twice a day from day 15 through day 20 of gestation, a period in development that is critical for sexual differentiation of the male rat brain. No differences in litter size, number of stillborns, or body weight were observed in offspring from field-exposed dams. At 120 days of age, field-exposed male offspring exhibited significantly less scent marking behavior than controls. Accessory sex organ weights, including epididymis, seminal vesicles, and prostate, were significantly higher in field-exposed subjects at this age. However, circulating levels of testosterone, luteinizing hormone, and follicle stimulating hormone, as well as epididymal sperm counts, were normal. These data indicate that brief, intermittent exposure to low-frequency EM fields during the critical prenatal period for neurobehavioral sex differentiation can demasculinize male scent marking behavior and increase accessory sex organ weights in adulthood. PMID- 2106175 TI - Induction of postaxial forelimb ectrodactyly with anticonvulsant agents in A/J mice. AB - Exposure of A/J mice on day 9.5 of gestation to the derivatives of three acidic anticonvulsant agents, namely dimethadione, sodium valproate, and sodium diphenylhydantoin, each induced postaxial forelimb ectrodactyly predominantly of the right side. This specific malformation has previously been associated with the administration of acetazolamide to rodents; however, several agents can induce this same defect including other carbonic anhydrase inhibitors, carbon dioxide, cadmium, ethanol, ammonium chloride, and 13-cis retinoic acid. The relative potency of the three agents indicates no direct relationship to the pKa of the acid. Other than ectrodactyly, each of the anticonvulsant agents induced a compound-specific spectrum of malformations despite the uniform administration time. This finding suggests that these agents are capable of acting via different mechanisms or by the differential spatial and temporal dynamics of a common mechanism. PMID- 2106176 TI - Arachidonic acid metabolism and pathophysiologic aspects of subarachnoid hemorrhage in rats. AB - We studied the ex vivo production of prostaglandin D2, prostaglandin E2, 6 ketoprostaglandin F1 alpha, and leukotriene C4 in the brain tissue of rats subjected to experimental subarachnoid hemorrhage. The ex vivo method allows the study of arachidonic acid metabolites released from brain slices at different times after subarachnoid hemorrhage induction and reflects the residual capacity for arachidonic acid metabolism after the pathologic event. The rats were sacrificed 30 minutes, 1 and 6 hours, and 2 days after subarachnoid hemorrhage was induced by the injection of 0.30 ml autologous arterial blood into the cisterna magna. Concentration of prostaglandin D2 and 6-ketoprostaglandin F1 alpha was increased significantly relative to control 2 days after induction. The concentration of prostaglandin E2 was increased significantly 6 hours after induction, while ex vivo production of leukotriene C4 was increased significantly at 1 and 6 hours and 2 days. The correlation between these results and the occurrence of vasospasm after subarachnoid hemorrhage is discussed. The results obtained from the ex vivo incubation of brain tissue slices after experimental subarachnoid hemorrhage suggest that after the hemorrhage there is a significant modification of brain eicosanoid metabolism, which could be of great importance in interpreting the pathogenesis of subarachnoid hemorrhage-related neuronal impairment. PMID- 2106177 TI - Group A variants defined with a monoclonal anti-A reagent. AB - Unusual serologic findings mimicking the B(A) phenomenon were noted in two group B blood donors using blended murine monoclonal anti-A reagent. With additional studies, including a binding experiment using affinity chromatography, the presence of aberrant group A activities was confirmed. This observation suggests that persons with atypical B(A) phenotype may warrant further investigation to delineate the ABO blood group. PMID- 2106178 TI - Prolonged storage of red cells with ammonium chloride and mannitol. AB - Recently, a new preservation medium consisting of ammonium chloride added to adenine, glucose, mannitol, citrate, and potassium phosphate, was described. Unexpectedly, the predominant effect on red cell storage was an initial elevation of ATP levels, followed by remarkable maintenance of these levels at 12 to 18 weeks with acceptable 24-hour survival. The aim of the study reported here was to investigate the reasons for the advantageous effects of the different constituents. With the new preservation medium, ATP content was maintained at acceptable levels for at least 8 weeks with low spontaneous hemolysis. However, similarly high ATP levels were also maintained in the absence of ammonium chloride. Comparable results were obtained on substituting sodium for potassium salts in the new medium. When the main cation in the preservation medium was replaced by sodium, the addition of ammonium or rubidium chloride did not provide an advantage. Therefore, ammonium chloride was not essential for this medium, whereas mannitol does seem to be essential in a solution whose content of nonpermeant solutes is hypotonic. PMID- 2106179 TI - The effect of islet cell culture in vitro at 24 degrees C on graft survival and MHC antigen expression. AB - A period of in vitro culture prior to transplantation has been shown to prolong the survival of many types of MHC-incompatible endocrine grafts. The effectiveness of this strategy has been attributed to a selective depletion of intragraft antigen-presenting cells. We report that in vitro culture at 24 degrees C results in a significantly better survival of rat isolated islet allografts than does culture at 37 degrees C. Using in vitro assays of APC activity, we were unable to detect differences in the quantity of residual intraislet APCs between 24 degrees C and 37 degrees C culture preparations. In contrast, islet endocrine cells cultured at 24 degrees C evidenced a reduced level of cell surface class I MHC antigen expression and were significantly less vulnerable to lysis in vitro by CTL. These findings suggest that culture at 24 degrees C produces islet alterations other than APC depletion, and that its beneficial effect on graft survival correlates with a reduction in endocrine cell class I MHC antigen expression. PMID- 2106180 TI - Cyclosporine and anti-interleukin 2 receptor monoclonal antibody therapy suppress accelerated rejection of rat cardiac allografts through different effector mechanisms. AB - Increasing numbers of sensitized patients are either precluded from receiving an allograft or experience accelerated rejection which may be refractory to conventional therapy. Using a rat model, we have shown that accelerated (24 hr) rejection of LBN cardiac Tx in LEW rats sensitized with BN skin grafts 7 days earlier, could be prevented by treatment with cyclosporine (15 mg/kg/day x7 days, Tx survival about 42 days) or ART-18, an anti-IL-2R mAb (300 micrograms/kg/day x10 days i.v., Tx survival about 16 days). In this study, we evaluated intragraft mechanisms responsible for these effects by immunoperoxidase localization of relevant humoral mediators (IgG, IgM, C3, cross-linked fibrin), graft infiltrating cells (GIC), and associated cytokines (IL-2, IFN-g, tumor necrosis factor [TNF], or cytokine receptors (IL-2R). Tx rejected in fulminating fashion by 24 hr in sensitized hosts showed extensive and progressive endothelial deposition of IgG, C3, and fibrin from 2 hr, followed by an influx of neutrophils at 3 hr, and peak numbers of GIC by 18 hr (88.8 +/- 20.3 leukocytes/field). At 18 hr, GIC consisted of neutrophils (26%), T cells (20%, greater than 90% of which were OX-8+), and monocytes/macrophages (53%), whereas B cells were absent. By 18 hr, up to 20% of GIC were IFN-g+, 10% were IL-2R+, and 10% were IL-2+, consistent with labeling of 20% of cells with OX-22. Widespread endothelial and mononuclear cell labeling for TNF and the procoagulant molecular tissue factor (TF) were also noted. In contrast to untreated grafts, CsA treatment essentially abolished intragraft Ig, C3, and fibrin deposition. Moreover, despite dense cell infiltration at 24 hr (total GIC 55.3 +/- 13.4/field), analysis of CsA-treated Tx showed markedly decreased neutrophils (0.5%), with increased T cells (35%) and similar proportions of macrophages (66%). In addition to the reduction in neutrophils, Ig and C3, fewer IL-2R+ (6%) and OX-22+ (3%) cells, considerably less TNF and TF, and almost no IL-2+ or IFN-g+ GIC (less than 1%) were detected. Surprisingly, ART-18 treatment also greatly decreased but did not abolish endothelial deposition of C3, IgG, or IgM, whereas widespread endothelial and mononuclear labeling for fibrin, TNF, and TF remained. In addition, GIC (about 54.8 +/- 16.1/field) contained only moderately reduced numbers of neutrophils (31%) and the proportions of T cells (27%) and macrophages (49%) were generally comparable to those of rejecting Tx in untreated rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2106181 TI - Enterically transmitted non-A, non-B hepatitis associated with an outbreak in Dhaka: epidemiology and public health implications. AB - Investigation of an outbreak of hepatitis in Dhaka implicated enterically transmitted non-A, non-B (ET-NANB) hepatitis as the etiologic agent. This observation was made by exclusion in 17 of 19 patients, and confirmed serologically in one randomly selected patient by a fluorescent antibody blocking assay specific for ET-NANB hepatitis. These findings reinforce earlier suspicions that ET-NANB may be an important cause of acute hepatitis in Bangladesh. The epidemiology of ET-NANB hepatitis is discussed, and public health recommendations are made. PMID- 2106182 TI - Vulvar Schistosoma haematobium lesion treated with praziquantel. PMID- 2106183 TI - Female urologic diagnostic techniques. AB - With the exception of stress incontinence, the most common urologic problems unique to female patients are vesicovaginal fistulas and urethral diverticula. The author describes modifications of a Foley catheter both to facilitate distention of the vagina for vaginoscopy and for urethrography and use of the visual urethrotome for urethroscopy. PMID- 2106184 TI - Congenital urethral and vesical diverticula allied to blind-ending ureters. AB - Blind-ending ureter is a well-recognized but rarely addressed abnormality that results in the urethral or bladder diverticulum. A girl and a boy are described with urethral diverticulum and bladder diverticulum, respectively, which are believed to be allied to blind-ending ureters. PMID- 2106185 TI - Testicular veins: anatomy and role in varicocelogenesis and other pathologic conditions. AB - The anatomy of the testicular veins of 42 male cadavers were studied to determine the extent of their role in varicocelogenesis and other pathologic conditions. The results of that study are presented. PMID- 2106186 TI - A novel effect of adenovirus VA RNA1 on cytoplasmic mRNA abundance. AB - Adenovirus VA RNA1 is a small RNA polymerase III transcript that enhances mRNA translation both in transfected cells and during a lytic virus infection. Here we present evidence that VA RNA1 also, in length-dependent manner, increases cytoplasmic mRNA abundance in transient expression assays in 293 cells. PMID- 2106187 TI - [alpha 1-proteinase inhibitor in breast cancer]. AB - Level of alpha 1-proteinase inhibitor (alpha 1-Pi) and antitryptic activity in blood serum were assessed in 167 patients with breast cancer and 30 cases of benign lesions. An increase in blood serum-alpha 1-Pi level was shown to be associated with tumor advancement but could not be regarded as a marker of cancer. Concentration of the inhibitor exceeded 8 mg/ml in 83.4% of cases with metastatic breast cancer but was as a rule, equal to or below that value in metastasis--free patients. Those two groups were prognostically different. Morphological analysis established a correlation between blood serum-alpha 1-Pi level, on the one hand, and grade of malignancy, degree of pathologic changes in tumor stroma and extent of lymph node involvement, on the other. PMID- 2106188 TI - Failure of pyridostigmine to increase both basal and GHRH-induced GH secretion in the night. AB - The aim of this study was to verify that the stimulatory effect of cholinergic agonists on both basal and stimulated GH release observed in the morning persists in the night. The effects of pyridostigmine (120 mg orally), a cholinesterase inhibitor, on both basal and GHRH (1 micrograms/kg iv)-induced GH secretion were studied in 8 healthy volunteers, aged 22-30 years. In the morning, administration of pyridostigmine induced a significant increase in basal GH levels compared with saline (area under the response curve, mean +/- SEM: 277.0 +/- 54.0 vs 49.7 +/- 8.2 micrograms.l-1.h-1, p less than 0.02) as well as a strong potentiation of the GHRH-induced GH release (2117.6 +/- 353.0 vs 427.9 +/- 87.0 micrograms.l-h-1, p less than 0.02). In the night, GH secretion after pyridostigmine did not differ from saline (194.5 +/- 21.9 vs 89.4 +/- 28.7 micrograms.l-1.h-1). Moreover pyridostigmine failed to potentiate the GHRH-induced GH increase (1071.9 +/- 170.4 vs 740.2 +/- 150.9 micrograms.l-1.h-1). The pyridostigmine + GHRH-induced GH rise during the night was lower (p less than 0.05) than in the morning. All together, these data seem to indicate that cholinergic neurons controlling GH secretion are already maximally stimulated at night. As cholinergic activity negatively modulates SRIH secretion, our findings suggest that a reduced somatostatinergic tone in the hypothalamus is present during the night. PMID- 2106189 TI - Induction of experimental thyroiditis in mice by recombinant interferon gamma administration. AB - Expression of major histocompatibility complex (MHC) class 2 molecules on the thyroid follicular cells in human autoimmune thyroid diseases has been reported, and is suggested to play a role in the initiation of the autoimmune responses. Interferon gamma is known to induce MHC class 2 molecules on cultured thyrocytes. Therefore, we administered recombinant interferon gamma to mice to induce MHC class 2 molecule expression in vivo, and investigated the thyroidal changes following MHC class 2 molecule expression. Recombinant interferon gamma 3 x 10(5) U, was administered daily, to mice. MHC class 2 molecules, studied by indirect immunohistochemistry, were expressed on the follicular cells on the 2nd to 4th day after the first interferon gamma administration and continued thereafter. Serum T4 and T3 concentrations decreased and anti-thyroglobulin antibodies and anti-microsomal antibodies were detected. Lymphocyte infiltrations were observed in the thyroid glands obtained at 28 days, but they were mild. These results suggest that MHC class 2 molecule expression on thyroid follicular cells induces anti-thyroid antibodies and plays an important role in the initiation of autoimmune thyroiditis. However, the progression of the immune response to thyroiditis with lymphocyte infiltration may require some other factor. This new model of autoimmune thyroid disease in mice might be useful to elucidate the pathogenesis of human autoimmune thyroid diseases. PMID- 2106190 TI - Enhanced testosterone secretion in adult rams after establishment of a high frequency, low-amplitude pattern of LH pulses in the nonbreeding season occurs without changes in the number or binding affinity of testicular LH receptors. AB - When the LH signal in the ram is changed from one of large and infrequent pulses to one of small and frequent pulses, the testes quickly become more responsive to LH and testosterone secretion is elevated, perhaps because the number and (or) binding affinity of testicular LH receptors have increased. An experiment was undertaken in the nonbreeding season (July) with 10 adult Dorset x Leicester x Suffolk rams that were about 3.5 years of age and 69 +/- 2 kg in body weight. Rams were given injections into the jugular vein of either 5 micrograms NIH-LH S24 (in 1 ml saline) or vehicle every 80 min for 6 days. LH treatment produced a series of LH pulses that occurred three times more frequently and were 70% less in amplitude than pulses in the control rams, without causing mean LH concentration to increase. Endogenously produced LH pulses were not evident in the treated rams after LH injection began. The modified LH-pulse pattern elevated mean testosterone concentration by 150% (assessed on days 2 and 5), and caused the cumulative testosterone response to LH pulses, estimated by multiplying testosterone-pulse amplitude by frequency per 6 h, to increase progressively by 180% (days -2 through 5). Enhanced testicular steroidogenic activity, presumably due to greater enzymatic activity and cholesterol availability within Leydig cells, was not associated with increases in either the concentration or affinity of LH-binding sites in the testis (assessed on days 3 and 6). PMID- 2106191 TI - Effect of oral clonidine, insulin-induced hypoglycemia and exercise on plasma GHRH levels in short-stature children. AB - Human growth hormone release is affected by a variety of pharmacological and physiological stimuli. We have studied the effect of oral clonidine, insulin hypoglycemia, and exercise on plasma hGH and GHRH levels in 31 healthy short stature children. Thirteen underwent an oral clonidine test (0.15 mg/m2), 12 an iv. insulin test (0.1 U/kg), and 6 performed exercise (running for 10 min in a defined route). GHRH-1-44 was extracted from plasma on silica columns and determined by RIA. Although all three stimuli induced a marked increase in plasma hGH levels, only clonidine induced a significant increase in plasma GHRH levels. Maximal increment in GHRH during clonidine was 6.82 +/- 1.05 pmol/l (mean +/- SEM) as compared with 0.51 +/- 0.28 and 0.53 +/- 0.62 during hypoglycemia and exercise (p less than 0.0005 and p less than 0.005), respectively. An additional 24 subjects received TRH 0.2 mg/kg iv: 8 TRH alone, 8 TRH and insulin, and 8 TRH and clonidine. Only insulin potentiated the TRH-induced TSH response with a peak of 22.0 +/- 3.2 vs 16.0 +/- 0.8 and 15.3 +/- 1.5 mU/l (p less than 0.025) for TRH alone and TRH and clonidine, respectively. It is suggested that clonidine stimulates hGH secretion mainly through an enhancement of GHRH release, whereas stress stimuli such as hypoglycemia and exercise achieve hGH release by a different mechanism, possibly inhibition of somatostatin. PMID- 2106192 TI - Follicle-stimulating hormone stimulates inhibin in the serum of male monkeys (Macaca mulatta). AB - Three adult rhesus monkeys were injected intramuscularly with human FSH at doses of 2, 10 or 25 IU/kg in a cross-over design with 3-week intervals between injections. On each occasion a fourth animal received saline only as control. Serum levels of exogenous FSH were monitored by a fluoroimmunoassay specific for human FSH. Serum inhibin was measured by a heterologous radioimmunoassay. Each FSH injection was followed by a rise in serum inhibin in a dose-dependent manner. The half-life of human FSH in rhesus monkeys ranged from 25.1 to 32.9 h with no significant differences between doses. The rise of inhibin occurred with a lag time of 53.3 to 61.9 h after injection of FSH, independent of the dose administered. These findings support the concept that inhibin secretion in male primates is stimulated by FSH. PMID- 2106193 TI - Important variations of maternal anti-Rhesus (D) antibody level during two consecutive pregnancies without antigenic stimulus. AB - In many cases, during pregnancies of anti-D alloimmunized women, without antigenic stimulus, the anti-D concentration remains stable. We report here a case of a woman anti-D and anti-C alloimmunized which has presented high variation of anti-D concentration in her serum during two successive pregnancies with a Rh-negative fetus. Thus, the Liley Index only has confirmed the absence of fetal damage. PMID- 2106194 TI - Abnormality of platelet membrane glycoprotein GPIIb in a myelodysplastic syndrome with 3q inversion presenting with marked dysmegakaryopoiesis. AB - Platelet membrane glycoproteins were analyzed in a case of myelodysplastic syndrome with inv(3) (q21q26) presenting with prominent dysmegakaryopoiesis by three different labelling techniques for surface proteins. Markedly decreased level of platelet membrane glycoprotein GPIIb was observed in the patient's platelets by terminal sialic acid labelling method, whereas no significant changes in the levels of glycoproteins including GPIIb could be detected either by penultimate galactose labelling or by tyrosine/histidine labelling. These results indicate a decreased sialylation of GPIIb in the patient's platelets, implying aberrant process in thrombopoiesis in the disease. PMID- 2106195 TI - Pregnancy, antithrombin III deficiency and venous thrombosis: report of another case. PMID- 2106196 TI - Cyclosporin for refractory aplastic anemia. PMID- 2106197 TI - Indium-111 oxine technique of studying platelet aggregation in vivo. Some physiological considerations. AB - Intravascular aggregation in response to ADP, thrombin, arachidonate and collagen has been studied in the rat with a view to throwing more light on the validity, the reproducibility and physiology of the model. The radioisotopic technique of labelling platelets with indium-111 oxine was employed. The model is minimally invasive and involves collecting blood from donor rats, separating and labelling their platelets with indium-111 oxine and assessing the accumulation of platelets in the lungs of recipient rats following the intravascular administration of aggregating agents. Of the parameters evaluated, percentage peak increase in radio-labelled platelet count and area under the curve are good parameters of expressing aggregatory responses. Of the visceral organs evaluated, the lung is the most important organ for assessing platelet accumulation. Of the vascular routes examined, no aggregatory response occurred in the lungs when ADP was injected via any of the intra-arterial routes, and of the intravenous routes, injection via the tail vein gave the highest response. The results of this investigation provide some more detailed technical information to take note of when studying platelet aggregation in vivo by this model. The results also highlight the physiological phenomenon involved. PMID- 2106198 TI - High-dose intravenous immunoglobulin in the management of autoimmune hemolytic anemia complicating thalassemia major. AB - Patients with thalassemia major due to red blood cell autoantibodies may develop an increase in transfusional blood consumption. In this study we report the results of treatment with high intravenous immunoglobulin (Ig) in 4 patients who developed an increase in blood consumption related to the presence of autoantibodies of defined or undefined specificities. Three patients showed a normalization of the blood consumption. No adverse effects were detected. These results indicate that high-dose intravenous Ig therapy is indicated in patients with thalassemia major manifesting an increase in blood consumption following the development of red cell autoantibodies. PMID- 2106199 TI - Immunologic evaluation of children with homozygous beta-thalassemia treated with desferrioxamine. AB - In 15 children with thalassemia major (age 4-17 years) a detailed analysis of different immune functions was performed: phagocyte function, specific cellular immunity, humoral defense system. All patients had been subjected to a desferrioxamine therapy and a high transfusion regimen. Examination of neutrophil function included adherence, random migration, chemotaxis, killing of Escherichi coli and production of superoxide radical; these neutrophil functions were shown to be normal. In addition, lymphocyte proliferation in response to different lectins (phytohemagglutinin, concanavalin A, pokeweed mitogen) was identical in patients and controls. However, the number of circulating T-lymphocytes, helper T cells and B-lymphocytes was increased in some patients. This phenomenon probably reflects an unspecific stimulation of the antibody-producing cells by repeated blood transfusions. PMID- 2106200 TI - Etoposide in remission induction of adult acute myeloid leukemia. AB - 96 consecutive acute myelogenous leukemia (AML) patients were analyzed retrospectively with regard to the regimen used for remission induction. 35 patients received daunorubicin for 3 days, cytosine arabinoside and 6-thioguanine for 7 days. 61 were treated with the same regimen but 6-thioguanine was replaced by etoposide. Complete remission was achieved in 57 and 72% of patients, respectively (p = 0.06). In leukemias with monocytic phenotype (M4-M5), the remission rate was significantly higher with the etoposide-containing regimen (p = 0.02). Our findings suggest that the replacement of thioguanine by etoposide could be useful in induction therapy of AML. PMID- 2106201 TI - Successful zidovudine therapy for HIV-related severe thrombocytopenia. Report of a sustained remission. AB - Five patients, two homosexuals and three drug abusers, with HIV-related severe thrombocytopenia, four of whom had also bleeding episodes, experienced a full remission of thrombocytopenia after 1,200 mg/day zidovudine treatment. None of the patients had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Platelet counts began an upward trend at the end of the 3rd week and reached values higher than 140 x 10(9)/l towards the end of the 8th week of treatment. Patient's platelets remained stable after more than 4 months of active treatment. This is the first report of zidovudine-induced long-term remission of HIV-associated severe thrombocytopenia. PMID- 2106202 TI - Chronic neutrophilic leukaemia preceding for seven years the development of multiple myeloma. PMID- 2106203 TI - Thrombocytopathy due to a defect of the platelet membrane complex. AB - A new type of primary thrombocytopathy is described. Three main alterations were found: (1) a defect of the aggregation reaction with ADP, epinephrine and collagen and a normal response to ristocetin and arachidonic acid; (2) a moderate deficiency of platelet procoagulant activity, and (3) a combined hypertrophy of the two membrane systems of the platelet--the open canalicular and the dense tubular. The latter defect is shown as an abnormal membrane complex situated on one of the platelet poles. This thrombocytopathy is discussed as a new variety of primary platelet disorder. PMID- 2106204 TI - Ontogeny of relationship of middle ear and temporomandibular (squamomandibular) joint in mammals. III. Morphology and ontogeny in scandentia and primates. AB - The ontogeny of the mandibular joint and the middle ear region was studied in Tupaia javanica, Microcebus murinus, Nycticebus coucang and Tarsius bancanus. During development, a passage connection was found between the mandibular condyle and Meckel's cartilage that is produced by the primordium of the lateral pterygoid muscle. The articular disk is formed separately, and it appears later in development. A theory is presented on the interpretation of these findings. PMID- 2106205 TI - Monochorionic twinning: sonographic assessment. PMID- 2106206 TI - Identification of retained firearm projectiles on plain radiographs. PMID- 2106207 TI - A tutorial on confidence intervals for proportions in diagnostic radiology. PMID- 2106208 TI - Do chest radiographic findings reflect the clinical course of patients with sarcoidosis during corticosteroid withdrawal? AB - The use of serial chest radiographs to assess disease activity in patients with sarcoidosis is controversial. However, reliance on the symptomatic clinical course to assess disease activity may be misleading. As many patients being treated with corticosteroids have an abrupt clinical deterioration when doses of those medications are decreased, we questioned whether the chest radiograph could depict alterations in disease activity as measured by spirometry in this subset of patients. We retrospectively reviewed the clinical course of all patients with pulmonary sarcoidosis in whom the corticosteroid dose was reduced during a 6 month period. The 15 patients without fever, chills, or purulent sputum during that time were then examined to determine the presence (n = 10) or absence (n = 5) of a symptomatic relapse. All patients who had a symptomatic relapse also had a fall in forced vital capacity of at least 10%, suggesting an increase in disease activity. Serial chest radiographs were evaluated during and after corticosteroid dose reductions and after clinical recovery on higher steroid doses in the patients who had had a relapse. In eight patients, the disease was in radiographic stage 2 (hilar adenopathy and parenchymal lung disease); in seven patients it was in radiographic stage 3 (parenchymal lung disease alone). The disease did not change stage in any patient during the study. Chest radiographs worsened more frequently in patients who had a clinical relapse (seven of 10) than in those who did not have a relapse (zero of five, p less than .05). An alveolar chest radiographic pattern (n = 4) or reticulonodular pattern (n = 3) was noted in the seven patients who had a relapse, with worsening on radiographs often occurring before detection of relapse by symptomatology (four of seven) or spirometry (three of seven). Spirometry and radiographs improved or stabilized after an increase in corticosteroid dose in all 10 patients who had a relapse. We conclude that serial chest radiographs can reflect clinical relapse in patients with sarcoidosis during corticosteroid dose reduction. Furthermore, worsening seen on chest radiographs may be the first evidence of relapse. PMID- 2106209 TI - CT in differential diagnosis of diffuse pleural disease. AB - The CT features of benign and malignant pleural diseases have been described. However, the accuracy of these features in the differential diagnosis of diffuse pleural disease has not been assessed before. Without knowledge of clinical or pathologic data, we reviewed the CT findings in 74 consecutive patients with proved diffuse pleural disease (39 malignant and 35 benign). The patients included 53 men and 21 women 23-78 years old. Features that were helpful in distinguishing malignant from benign pleural disease were (1) circumferential pleural thickening, (2) nodular pleural thickening, (3) parietal pleural thickening greater than 1 cm, and (4) mediastinal pleural involvement. The specificities of these findings were 100%, 94%, 94%, and 88%, respectively. The sensitivities were 41%, 51%, 36%, and 56%, respectively. Twenty-eight of 39 malignant cases (sensitivity, 72%; specificity, 83%) were identified correctly by the presence of one or more of these criteria. Malignant mesothelioma (n = 11) could not be reliably differentiated from pleural metastases (n = 24). We conclude that CT is helpful in the differential diagnosis of diffuse pleural disease, particularly in differentiation of malignant from benign conditions. PMID- 2106210 TI - Cavitary pulmonary metastases in transitional cell carcinoma of urinary bladder. PMID- 2106211 TI - Reactivation of tuberculosis in a donor lung after transplantation. PMID- 2106212 TI - Ileocecal tuberculosis: CT and radiologic evaluation. AB - The CT and radiologic findings in 11 patients (five with AIDS and six without AIDS) with ileocecal tuberculosis are described. On CT scans, five cases showed mild circumferential wall thickening of the terminal ileum and cecum, thickening of the ileocecal valve, and a few regional nodes. One case presented as nonspecific small-bowel obstruction. In five patients a more characteristic CT appearance was detected: preferential thickening of the ileocecal valve and medial wall of the cecum, exophytic extension engulfing the terminal ileum, and massive lymphadenopathy with low-density areas consistent with caseation necrosis. Patients with AIDS had a more severe form of involvement than those who did not have AIDS. Barium studies showed ileocecal changes consistent with an inflammatory process. In conjunction with barium enema, CT is helpful in the initial evaluation of ileocecal tuberculosis, showing the location and extent of intestinal and mesenteric involvement in most cases. Characteristic CT findings are seen when the inflammatory process is severe. PMID- 2106213 TI - Gallbladder contractility in patients with spinal cord injuries: a sonographic investigation. AB - Approximately 30% of all patients who have spinal cord injuries have gastrointestinal symptoms. One cause is gallstone disease; indeed the literature suggests that gallstones are more common in patients with spinal cord injuries because these patients have impaired contractility of the gallbladder with a reduced ejection fraction. To test this hypothesis, we obtained gallbladder sonograms in 30 patients with spinal cord injuries (16 quadriplegics and 14 paraplegics) and in 32 uninjured age-matched control subjects. Four patients and four asymptomatic control subjects had gallstones and were excluded. The remaining 26 patients and 28 control subjects fasted for 12 hr. Longitudinal and transverse sonograms of the gallbladder were made immediately before the ingestion of 25 g of fat, and at 10, 20, 30, 45, and 60 min thereafter. Gallbladder volumes were measured by using the ellipsoid method. Resting and residual volumes and the emptying times were determined and the ejection fractions were calculated. The ejection fractions were significantly lower (p = .003) in the patients than in the control subjects because the resting volumes were lower than in the control subjects (p = .013). However, the emptying times and residual volumes were the same in the two groups. We conclude that gallbladder contractility is normal in patients with spinal cord injuries and that the lower ejection fraction found in such patients is due to a smaller resting volume. PMID- 2106214 TI - Hydatid disease of the spleen: imaging findings in nine patients. AB - Splenic involvement is uncommon in patients with hydatid disease. The radiologic and clinical findings in nine patients with splenic hydatidosis are described. The three men and six women were 41-76 years old (mean, 58 years). Their histories and physical findings, the results of serologic tests for hydatidosis, and imaging procedures were evaluated. Plain abdominal radiographs were obtained in all nine patients, sonograms in six, and CT scans in seven. Plain films showed calcification of the cyst wall in four of the nine patients. On sonograms, five lesions were anechoic and one was echogenic. On CT scans, all lesions except one were of lower attenuation than the surrounding spleen. None of the lesions enhanced after administration of IV contrast material. Although rare, splenic hydatidosis should be included in the differential diagnosis when a cystic splenic lesion is identified with sonography or CT. PMID- 2106215 TI - Acute venous thrombosis after pancreas transplantation: diagnosis with duplex Doppler sonography and scintigraphy. PMID- 2106216 TI - Treatment of acute esophageal food impaction with a combination of glucagon, effervescent agent, and water. PMID- 2106217 TI - Prevalence and significance of subchorionic hemorrhage in threatened abortion: a sonographic study. AB - We performed a prospective study to determine the prevalence and significance of subchorionic hematomas in patients with symptoms of threatened abortion. The study comprised 342 pregnant women who had vaginal bleeding in weeks 9-20 of pregnancy and a live fetus shown with sonography. Sonograms showed a subchorionic hematoma in 62 patients (18%). The average size of the hematoma was 20 ml (range, 2-150 ml). The rate of spontaneous abortion was the same in patients with and without hematoma, seven (11%) of 62 and 28 (10%) of 280, respectively. There was no association between abortion rate and hematoma size. The rate of premature delivery was the same in patients with and without hematoma, seven (11%) of 62 and 32 (11%) of 280, respectively. There was no association between the rate of premature delivery and hematoma size. Subchorionic hematomas are common and insignificant sonographic findings in patients with vaginal bleeding in weeks 9 20 of pregnancy. PMID- 2106218 TI - Differentiation of seminomatous from nonseminomatous testicular tumors with MR imaging. AB - Distinguishing seminomatous from nonseminomatous testicular neoplasms preoperatively is useful because treatment of these two tumors types is different. We evaluated whether the distinction could be made with MR imaging in six patients with seminomatous and nine patients with nonseminomatous testicular tumors (including teratoma, teratocarcinoma, embryonal cell, and choriocarcinoma). The MR diagnoses, which were obtained from the formal reports of the MR studies done and interpreted before orchiectomy, were compared with the pathologic diagnosis. The distinction between the two tumor types on MR images was based on the signal intensity and heterogeneity of the lesion. We also retrospectively compared the MR findings with tissue histology. MR scans in nonseminomatous tumors showed a marked heterogeneous mix of signals, with some regions less intense and others more intense than normal testicular tissue on both proton-density and T2-weighted images. The typical background signal was nearly equal to normal testicular tissue. The tumors also had a dark band at their periphery that correlated with a fibrous tumor capsule on histologic examination. In contradistinction, seminomatous tumors were isointense with testis on proton-density images and consistently hypointense and relatively homogeneous on T2-weighted images. These tumors typically lacked a capsule on MR images. One lesion, only 3 mm in diameter, could not be characterized on MR images because of limitations in spatial and contrast resolution. In 13 of the 14 lesions that could be characterized, the histologic type was predicted correctly on the basis of the MR appearance. The one error occurred in a patient with pure seminoma. Although the MR appearance of the lesion was otherwise similar to the other seminomas, the lesion had a single focus of bright signal that was due to hemorrhage. This focus was interpreted incorrectly as a nonseminomatous element. Our findings in this small series of patients suggest that MR imaging can be used to distinguish seminomatous from nonseminomatous testicular tumors. PMID- 2106219 TI - Value of transperineal sonography in the assessment of vaginal atresia. AB - We studied the value of transperineal sonography in the preoperative assessment of seven patients with clinically suspected vaginal atresia. Although transabdominal scanning is useful to determine if hydrocolpos or hydrometrocolpos is present, this method does not allow measurement of the thickness of a caudally placed obstructive septum. This information is useful in planning reconstructive surgery. All seven patients had transabdominal sonography, with five showing a low-lying obstruction. In those five patients, the distance between the perineal surface and the caudal aspect of the distended vagina, measured with electronic calipers on the transperineal sonograms, ranged from 1.0 to 4.0 cm. We conclude that when vaginal atresia is clinically suspected, transabdominal sonography should be performed to confirm the diagnosis. When a low-lying obstruction is identified, transperineal sonography should be performed to determine the length of the obstructive segment. PMID- 2106220 TI - MR imaging of the shoulder: correlation with plain radiography. PMID- 2106221 TI - Value of MR imaging in staging osteochondral lesions of the talus (osteochondritis dissecans): results in 14 patients. AB - Osteochondral lesions (osteochondritis dissecans) of the talus are common articular lesions that are usually traumatic in origin. Clinical management of these lesions is based on whether or not the fragments are attached. We studied the value of MR imaging in determining the stability of the osteochondral fragments. In 13 of 14 patients who had had correlative surgery, we accurately predicted the presence and extent of attachment of the fragment to the talus by performing preoperative MR imaging. The other patient had a false-positive diagnosis of a chondral fragment. All seven partially attached fragments had an irregular high-signal zone on T2-weighted images at the fragment/talar interface. The four unattached fragments had a complete ring of fluid surrounding the lesion. On the basis of these findings, we think MR of the ankle can be used to assess accurately talar osteochondral lesion stability and aid in clinical decision making. PMID- 2106222 TI - Subtalar arthrosis: evaluation with CT. AB - The surgical implantation of a Silastic wedge into the lateral subtalar joint (subtalar arthrosis) is designed to restrict the osseous malalignment associated with a flexible or neurogenic flatfoot deformity. We used CT to examine patients who had persistent pain after a subtalar arthrosis and retrospectively reviewed our experience with CT scans of 13 subtalar implants (seven patients) during a 3.5-year period. The CT scans of four asymptomatic subtalar implants showed each implant in the expected position and orientation, and the findings were considered normal. Conversely, the findings on CT scans of all nine painful implants (seven patients) were interpreted as abnormal. The scans showed oblique orientation of four implants (44%), loosening of three implants (33%), extruded methyl methacrylate in the subtalar joint in two implants (22%), and abnormal calcaneal recession in two implants (22%). Five of the nine painful implants were revised with improvement or resolution of symptoms. Our experience suggests that CT scanning of the subtalar joint can show the position and orientation of a subtalar implant and identify causes of persistent pain after a subtalar arthrosis. PMID- 2106223 TI - The significance of hematuria in children after blunt abdominal trauma. AB - The clinical significance of hematuria in children who sustain blunt abdominal trauma continues to be debated, as do the criteria for diagnostic imaging in this population. Previous reports have discussed the usefulness of certain clinical predictors of renal injury, such as the amount of hematuria present, the presence of shock or of head injury, and the presence or absence of symptoms or findings on physical examination. To assess the value of such predictors of renal injury in children with posttraumatic hematuria, we reviewed and analyzed the medical records and abdominal CT examinations of 256 children with blunt abdominal trauma. One hundred six children (41%) had hematuria. Thirty-five patients (14%) had renal injury that could be diagnosed by using CT. Nine of these had clinically significant injuries according to our criteria. We found a direct relationship between the amount of hematuria and the severity of renal injury. Hypotension at presentation occurred in 38 patients and was an insensitive predictor of renal injury. The combination of hypotension and hematuria was no more sensitive than hematuria alone in predicting renal injury. Sixty patients had concomitant craniofacial injuries. This subgroup had the same prevalence of hematuria and renal injury as the group that did not have head injuries. There were no clinically occult renal injuries in the study population. Furthermore, we found that no normotensive child with fewer than 50 RBCs per high-power field had a significant renal injury, and conversely, all children with significant renal injuries had either large amounts of hematuria or shock. PMID- 2106224 TI - False-negative duplex Doppler studies in children with hepatic artery thrombosis after liver transplantation. AB - Recent reports describe formation of collateral vessels in children who have hepatic artery thrombosis after liver transplantation. This led us to reevaluate the role of duplex Doppler imaging in this population. Among 135 pediatric liver transplant patients, 20 had arteriography for suspected hepatic artery thrombosis. Duplex and/or color Doppler imaging was performed in 13 of these children. The Doppler examination failed to show hepatic artery signals in five patients. Arteriography showed hepatic artery thrombosis in all five. In three of these, subsequent Doppler examinations showed reappearance of arterial Doppler signals. Arteriography confirmed the interval development of collaterals. Hepatic artery signals were found on the Doppler examinations of the remaining eight patients. Four had normal arteriograms, but the remaining four had hepatic artery thrombosis with collateral formation. Patients with hepatic artery thrombosis and collateral circulation tended to have increased diastolic flow (decreased resistive index). In addition, early scans clearly identified patients with complete thrombosis before collateral formation. On the basis of our preliminary experience, a child with a liver transplant and a clinical history strongly suggestive of hepatic artery compromise should have arteriography despite an apparently normal Doppler examination. PMID- 2106225 TI - MR imaging in patients with intractable complex partial epileptic seizures. AB - Detailed neurologic studies, high-field-strength MR imaging, and CT scanning were performed preoperatively in 53 patients with intractable complex partial seizures who underwent surgical treatment for epilepsy. Macroscopic structural (tumoral or vascular) lesions were found in 28% of patients. The remainder had pathologic findings consistent with mesial temporal gliosis. Tumors were found in 22% of the patients and were benign or of low-grade malignancy in every case. MR was accurate in the preoperative diagnosis of structural lesions, including very small occult tumors and cryptic vascular malformations. In patients with mesial temporal gliosis, there was correlation between the MR observation of a unilaterally dilated anterior temporal horn and the EEG-identified seizure focus and side of temporal lobectomy. However, MR demonstrated T2-weighted signal abnormalities correlating with the epileptogenic focus in only 8% of cases of mesial temporal gliosis. MR provided useful information in 28% of patients who underwent surgery for refractory complex partial epilepsy. MR obviated invasive EEG monitoring in 93% of the patients with structural lesions. MR was useful in only 8% of the patients with pathologic changes of mesial temporal gliosis. PMID- 2106226 TI - The cerebellum: 3. Anatomic-MR correlation in the coronal plane. AB - Thin (5-mm) coronal high-field (1.5-T) MR images of four human brain specimens and 14 normal volunteers were correlated with myelin-stained microtomic sections of the specimen cerebella. The primary white-matter tracts innervating several hemispheric (posterior quadrangular, superior, and inferior semilunar, gracile, biventer, tonsil) and vermian (declive, folium, tuber) lobules are oriented perpendicularly to the coronal plane of section and are shown well on proton density-weighted (long TR/short TE) and T2-weighted (long TR/long TE) spin-echo images, which provide excellent contrast between gray and white matter. Several of the surface sulci and fissures of the cerebellar hemispheres (including the superior posterior, horizontal, secondary, and posterolateral fissures) also course perpendicular to the coronal plane and are depicted well on T1-weighted (short TR/short TE) and T2-weighted images, which maximize contrast between CSF and parenchyma. The opportunity for side-to-side comparison of the hemispheres is a distinct advantage of the coronal view. Nevertheless, more obliquely oriented surfaces (preculminate, primary, inferior posterior, inferior anterior, and intrabiventral fissures) and deep hemispheric structures (primary white-matter tracts to central, anterior quadrangular, and floccular lobules) may be obscured by volume-averaging in the coronal plane; moreover, much of the finer anatomy of the vermis is depicted poorly. The constant surface and deep anatomy of the cerebellum revealed on coronal images in normal volunteers encourages detailed mapping. MR imaging in the coronal plane should be especially useful in identifying, localizing, and quantifying normal and abnormal morphologic differences between the cerebellar hemispheres. PMID- 2106227 TI - CT of intracranial cryptococcosis. AB - CT scans of 35 patients with intracranial cryptococcal infection were reviewed retrospectively. Studies were normal in 43% of the patients. Positive findings in others included diffuse atrophy in 34%, mass lesions (cryptococcoma) in 11%, hydrocephalus in 9%, and diffuse cerebral edema in 3%. Two unusual types of cryptococcoma were encountered, namely gelatinous pseudocysts and an intraventricular cryptococcal cyst. All findings were nonspecific for CNS cryptococcosis. The results suggest that CNS cryptococcosis should be considered in all patients at risk for the disease who have these abnormal CT findings, no matter what their initial clinical presentation. In addition, MR demonstration of gelatinous pseudocysts in one patient indicates that this technique may be helpful in locating cryptococcal mass lesions not visualized on CT. PMID- 2106228 TI - Intracranial ganglioglioma: MR, CT, and clinical findings in 18 patients. AB - Eighteen cases of pathologically proved intracranial gangliogliomas were reviewed to determine their MR, CT, and clinical characteristics. Seventeen patients were evaluated with contrast-enhanced CT and 14 were studied by MR imaging. Eight tumors were predominantly cystic; half of these demonstrated some contrast enhancement, and five contained calcifications. These cystic gangliogliomas were located, in order of decreasing frequency, in the cerebellum, temporal, frontal, and parietal lobes. Ten tumors were solid; eight of these showed contrast enhancement, and only one contained calcifications. Small cysts were present in one solid mass. Solid gangliogliomas occurred preferentially in the temporal lobes. On MR, the findings were nonspecific and reflected the CT findings. In one patient who received gadolinium-DTPA the lesion did not enhance. Clinically, all patients presented with nonfocal long-standing symptoms and all but three were alive an average of 18 months after the initial diagnosis. Pathologists are recognizing ganglioglioma with increasing frequency, and although its radiographic characteristics vary, it should be included in the differential diagnosis when the above-described findings are encountered. PMID- 2106229 TI - Treatment of iliac artery stenoses with the Wallstent endoprosthesis. AB - Sixteen symptomatic iliac artery stenoses and three occlusions in 16 patients were treated by the percutaneous implantation of Wallstent endoprostheses (Medinvent SA, Lausanne, Switzerland). The endoprosthesis consists of stainless steel monofilaments braided into a self-expanding cylinder. The indications for placement were restenosis after angioplasty (10 cases), failed arterial dilations (eight cases), and restenosis after endarterectomy (one case). The prostheses used had a mean diameter of 8 mm (range, 6-10 mm) and were placed in the external iliac (14 cases) and common iliac (five cases) arteries. The 16 stenoses were greater than 80%, and the three occlusions were longer than 7 cm. Mean length of the lesions treated was 7 cm (range, 4-14 cm). Three of the arteries thrombosed after treatment, one 2 days later and two in the month after implantation of the stent. On clinical and angiographic follow-up (mean, 16 months; range, 1-24 months) no symptoms or stenoses reappeared in the remaining 16 cases. Our experience in these cases suggests that implantation of a Wallstent endovascular prosthesis is a valuable technique for the treatment of external and common iliac artery stenoses. PMID- 2106230 TI - Removal of intimal hyperplasia in vascular endoprostheses by atherectomy and balloon dilatation. PMID- 2106231 TI - A simple device to facilitate percutaneous insertion of the Kimray-Greenfield filter. PMID- 2106232 TI - Artifacts in maximum-intensity-projection display of MR angiograms. PMID- 2106233 TI - Halo vest for cervical spine fixation during MR imaging. PMID- 2106234 TI - Ghost artifact on gradient-echo imaging: a potential pitfall in hepatic imaging. PMID- 2106235 TI - Planning a totally digital radiology department. PMID- 2106236 TI - Computer-aided management of residents' on-call and vacation schedules. PMID- 2106237 TI - Technology assessment: the contribution of professional organizations. PMID- 2106238 TI - Implications of technology assessment for the radiologist. PMID- 2106239 TI - Castleman disease of the greater omentum. PMID- 2106240 TI - Subcutaneous splenosis. PMID- 2106241 TI - Left intercostal approach for percutaneous biliary drainage after right trisegmentectomy. PMID- 2106242 TI - Transvaginal sonography in early pregnancy. PMID- 2106243 TI - Sonographic findings in crossed renal ectopia without fusion. PMID- 2106244 TI - Bone scans and ballet dancers. PMID- 2106245 TI - Enlarged parietal foramina and craniosynostosis in an American Indian child. PMID- 2106246 TI - Muscles of mastication. PMID- 2106247 TI - Incipient lingual cortical mandibular defect in a 10- to 12-year-old American Indian child. PMID- 2106248 TI - Automated filing of "teaching" radiographs under the ACR Index of Roentgen Diagnosis. PMID- 2106249 TI - Hypertension and radiation. PMID- 2106250 TI - Prototype AIDS vaccine works in monkeys. PMID- 2106251 TI - Pesticide glove permeation analysis: comparison of the ASTM F739 test method with an automated flow-through reverse-phase liquid chromatography procedure. AB - The results of two methods of analysis for measuring glove permeability to pesticides are reported. The standard ASTM F739-85 testing procedure was used to determine breakthrough times and permeation rates for four protective glove materials for two commercially available pesticide formulations. The same glove materials and pesticides then were tested using an in-house developed automated in-vitro diffusion analysis (AIDA) procedure. The ASTM and AIDA procedures both demonstrated no detectable breakthrough of Sevin 50W or 2,4-D Amine 96% for nitrile butyl rubber and polyvinyl chloride gloves. Although no breakthrough of Sevin 50W or 2,4-D Amine 96 was detected for natural rubber or neoprene gloves following the ASTM procedure, permeation was observed in 2 of 3 replicate tests for both rubber and neoprene gloves when using the AIDA method. The observed discrepancy may have been caused by a longer sampling duration for the AIDA method (16 hr) than the ASTM procedure (8 hr). Advantages of the AIDA procedure are discussed. PMID- 2106252 TI - Very early thrombolytic therapy in suspected acute myocardial infarction. The Thrombolysis Early in Acute Heart Attack Trial Study Group. AB - Three hundred fifty-two patients with suspected acute myocardial infarction (AMI) were randomized to placebo (175) or tissue-type plasminogen activator (rt-PA) (177). Patients were eligible if evaluated within 165 minutes from onset of chest pain and if age was less than 75 years. Electrocardiographic criteria were not required. A mobile coronary care unit with a cardiologist present was used to initiate treatment at home in 29% of the patients. Primary endpoints were infarct size (serum lactate dehydrogenase isoenzyme activity), left ventricular function (radioangiography) and exercise capacity at 30 days. AMI was diagnosed in 59% of all randomized patients. The incidence was similar in the 2 groups (placebo, 108, rt-PA, 101). Among all randomized patients, rt-PA was associated with significantly decreased infarct size and an increased ejection fraction. Among rt PA-treated patients there were significantly fewer Q-wave infarctions. No difference in exercise capacity could be detected. No benefit was found in subgroups of patients without ST-segment elevation on the initial electrocardiogram. There were 18 (10.3%) and 11 (6.2%) deaths (p = 0.23) within 30 days in the placebo and rt-PA groups, respectively. Adverse reactions were similar in both groups with no excess of complications in the home-treated group. Very early treatment with rt-PA in patients with a strong suspicion of AMI and ST segment elevation limits infarct size and improves left ventricular function. The infarct pattern is shifted from Q-wave to non-Q-wave infarcts by rt-PA. The study suggests that thrombolysis can be given before hospital admission without additional risk. Furthermore, electrocardiographic records are useful for selection of patients. PMID- 2106253 TI - Implications of the Cardiac Arrhythmia Suppression Trial for antiarrhythmic drug treatment. AB - The Cardiac Arrhythmia Suppression Trial (CAST) is a randomized, placebo controlled, double-blind, multicenter clinical trial involving 27 centers and more than 100 hospitals in North America and Europe to test the 1-tailed hypothesis that suppression of ventricular arrhythmias in patients with left ventricular dysfunction after myocardial infarction will reduce arrhythmic death. Since April 18, 1989, the CAST is enrolling patients aged less than 80 years with greater than or equal to 6 ventricular premature complexes and left ventricular ejection fraction less than or equal to 40%. Sustained ventricular tachycardia, class IV congestive heart failure or class IV angina pectoris are exclusion criteria. During a prerandomization period, antiarrhythmic drugs are titrated to suppress ventricular arrhythmias. If greater than or equal to 80% suppression is achieved during open-label titration, patients are randomized to the effective dose or to a matched placebo. If only partial suppression (1 to 79%) is achieved, patients are eligible for a substudy that randomizes them to the best dose found during open-label titration or to placebo. The only patients not randomized to treatment are those with increased arrhythmias or drug intolerance during titration. On April 18, 1989, encainide and flecainide were removed from the CAST because these drugs increased the death rate 2.5-fold. There were no imbalances in baseline risk variables between the encainide/flecainide group and the placebo group that might explain the adverse treatment effect. There was remarkable uniformity of the adverse effect across all subgroups. There were no subgroups that benefited from treatment; all were either harmed or not evaluable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106254 TI - Comparisons of efficacy and tolerance of moricizine with other antiarrhythmic agents in the treatment of chronic ventricular arrhythmias. AB - Comparative trials of a new drug with standard antiarrhythmic agents are important for establishing relative efficacy and tolerance. For moricizine, such trials have included comparisons with propranolol, disopyramide and quinidine. Furthermore, the Cardiac Arrhythmia Pilot Study compared moricizine in postinfarction patients with encainide and flecainide. These trials show moricizine to be superior in efficacy to a beta blocker (propranolol) and disopyramide and equivalent to quinidine. Although the class IC drugs (encainide and flecainide) showed somewhat greater efficacy in the Cardiac Arrhythmic Pilot Study, they are now known to increase the risk of mortality in postinfarction patients. Moricizine was also shown to be well tolerated in these trials and associated with fewer discontinuations than propranolol, disopyramide and quinidine. Thus, moricizine is a promising new agent when profiled against other drugs frequently used for therapy of chronic ventricular arrhythmias. PMID- 2106255 TI - Effect of temperature on the lactose hydrolytic capacity of a lactase derived from Kluyveromyces lactis. AB - In vitro studies of lactose hydrolysis in milk with 20-125 neutral lactase units (NLUs) carried out at 38.0 degrees C for 15 min with a beta-galactosidase derived from Kluyveromyces lactis (Lactaid, Lactaid Inc, Pleasantville, NJ) resulted in 85-95% of the hydrolysis observed with standard incubation conditions (24 h at 4 5 degrees C with 1000 NLU/L). Thirty-three lactose-maldigesting Guatemalan subjects, 16 children and 17 adults, were challenged with oral doses of lactose in milk (children aged less than 12 mo, 2 g/kg body wt; children aged 12-24 mo, 15 g/kg body wt; older children and adults, 18 g/kg body wt) preincubated for 20 min at 38 +/- 0.5 degrees C with 50-125 NLU Lactaid. Under these conditions the subjects consumed milk without presenting any signs of intolerance. Furthermore, their breath-hydrogen excretion showed a 91-93% reduction when compared with a similar load of milk containing nonhydrolyzed lactose. PMID- 2106256 TI - Recovery of labeled CO2 during the infusion of C-1- vs C-2-labeled acetate: implications for tracer studies of substrate oxidation. AB - In this study we determined the rate of conversion of carbon-labeled acetate to carbon dioxide in normal human volunteers and in anesthetized dogs. In human subjects (n = 4), [1-13C]acetate was infused on one occasion, and [2-13C]acetate was infused in the repeat study in the same subjects. In postabsorptive volunteers (n = 6), 81.2 +/- 6.5% (mean +/- SEM) and 53.1 +/- 7.4% of infused 13C was recovered as 13CO2 when [1-13C]- or [2-13C]acetate, respectively, were infused. In one subject studied during exogenous glucose infusion at 3.5 mg.kg 1.min-1, recovery of 13CO2 was 72.7% and 38.5% from [1-13C]- and [2-13C]acetate, respectively. In dogs, [1-14C]- and [2-13C]acetate were infused simultaneously. Recovery of 14CO2 was 75.9 +/- 2.5% of infused isotope whereas recovery of 13CO2 was 40.8 +/- 1.9%. We concluded that the position of the label in acetyl coenzyme A (CoA) determines the extent to which the process of oxidation of labeled acetyl CoA is reflected in labeled carbon dioxide excretion. PMID- 2106257 TI - Metastatic adenocarcinomas of unknown primary site. Prognostic variables and treatment results. AB - As part of a Phase II chemotherapy trial using mitomycin-C, adriamycin, and vindesine, 57 patients with adenocarcinoma of unknown primary site were assessed for prognostic variables predictive of response and survival. They were also evaluated for response and toxicity, usefulness of screening techniques, and eventual definition of primary site and pattern of progression. Only gender predicted response, with women being more likely to respond than men. Visceral metastases below the diaphragm, or the presence of liver metastases, predicted poor survival. Responding patients were highly likely to relapse first at sites of initial disease. Hemolytic-uremic syndrome was the most severe toxicity; other side effects were moderate. The response rate was 30% (three complete responders), which is similar to other current regimens. This study suggests that patients with better prognosis characteristics of single site of disease and without intraabdominal tumor may benefit from a policy of expectant observation after local control has been established. Patients with multiple sites of disease and/or intraabdominal tumor are appropriate candidates for investigational chemotherapy. PMID- 2106258 TI - Laboratory evaluation of jaundice in newborns. Frequency, cost, and yield. AB - Neonates with hyperbilirubinemia commonly undergo a battery of laboratory tests. We used a computerized database and medical records to study the frequency, cost, and yield of these tests in 2443 infants born at the University of California, San Francisco, between 1980 and 1982. Four hundred forty-seven (18%) of the infants met standard criteria for "nonphysiologic" hyperbilirubinemia; the incidence varied from 9% in blacks to 31% in Asian infants. About 55% of these 447 infants received a $125 "hyperbilirubinemia workup." Hospital discharge diagnoses on all 447 hyperbilirubinemic infants were reviewed. In 214 (48%), no cause of the jaundice was identified. An additional 145 (32%) had a possible cause apparent from history, physical examination, or initial hematocrit determination. The only diagnosis made as a result of routine investigations of hyperbilirubinemia was possible ABO or Rh isoimmunization in 75 infants (17%). Nonphysiologic hyperbilirubinemia may be more common than previously reported. The recommended tests are expensive and rarely lead to diagnoses other than ABO or Rh isoimmunization. Their routine use should be reevaluated. PMID- 2106259 TI - AIDS and infection control in forensic investigation. AB - Infection control in the workplace is becoming an increasingly important issue, not only for health care workers, but also for any workers who could potentially be exposed to infectious material. We discuss the nature, modes of transmission, and infectivity of important infectious agents likely to be encountered in the course of forensic investigations. We provide principles and guidelines for appropriate procedures and practices to be followed in a program of infection control. PMID- 2106260 TI - Compliance behavior and long-term maintenance dialysis. AB - Compliance with the therapeutic regimen is a critical and frequently confusing concept both for chronic renal failure patients and for care-givers. A panel group of maintenance dialysis patients was followed over a period of 9 years to identify the variables associated with positive or negative compliance behavior. Individual patient changes in adherence to the therapeutic regimen over time were also examined. Significant differences related to social support, especially when the demographic variable of education was controlled, were found. Serendipitous and surprising results were also documented when compliance behavior was evaluated in relation to patient mortality. From the analysis of quantitative and qualitative data, a typology of "ritual" versus "reasoned" compliance was derived. PMID- 2106261 TI - Monoclonal gammopathy and glomerulonephritis with organized microtubular deposits. AB - We report a case with IgG-kappa monoclonal gammopathy of unidentified significance (MGUS) and glomerulonephritis (GN) with organized microtubular deposits on electron microscopy (EM). Light microscopy (LM) examination showed exudative features and moderate extracapillary proliferation. An acute nephritic syndrome with a rapidly progressive renal failure was clinically manifest at the onset and during each relapse. The patient was treated with methylprednisolone pulses followed by oral prednisone, cyclophosphamide, plasmapheresis, and maintenance courses of chemotherapy. The response to treatment was good, with a temporary improvement of renal function and control of the downhill course over a 3-year follow-up. PMID- 2106262 TI - A new and improved guide to i.v. therapy. PMID- 2106263 TI - Rehabilitation of child molesters: a cost-benefit analysis. AB - This study examined the cost effectiveness of the rehabilitation of child molesters by designing and testing a cost-benefit model. The model uses program and reoffense data from a treatment center for offenders and costs derived from averaged figures obtained from state agencies. Results of the analysis, as well as related policy issues, are discussed. PMID- 2106264 TI - Effect of hyperosmotic challenge on basolateral membrane potential in rabbit urinary bladder. AB - In the rabbit urinary bladder, serosal hyperosmotic challenge (SHOC) with either 33 mM NaCl or 66 mM mannitol caused basolateral membrane potential (Vbl) to initially depolarize from -52.6 +/- 1.6 to -48.4 +/- 1.4 mV, followed by a recovery of Vbl to -57.5 +/- 1.3 mV after 13.7 +/- 1.0 min. The voltage recovery was dependent on both serosal HCO3- and Cl-, and in the absence of both, Vbl depolarized to -11.6 +/- 1.5 mV and the ratio of apical-to-basolateral resistance (Ra/Rbl) decreased from 21.0 +/- 3.4 to 8.3 +/- 3.1. This decrease in Ra/Rbl and consequent depolarization of Vbl is caused by a decrease in basolateral K+ conductance. Replacement of serosal Cl- with NO3- or SCN- followed by SHOC caused a sustained depolarization of Vbl to -32.5 +/- 4.4 and -40.9 +/- 0.9 mV, respectively. However, when Br- was used to replace Cl-, voltage recovery occurred but was slowed (24.0 +/- 2.7 min) and reduced in magnitude (-47.5 +/- 3.5 mV). Addition of amiloride (1 mM) or niflumic acid (100 microM), but not bumetanide (1 microM), to the serosal bathing solution inhibited voltage recovery causing Vbl to depolarize to -36.3 +/- 2.6 and -41.5 +/- 4.5 mV, respectively. Serosal addition of ouabain after SHOC caused Vbl to depolarize by 10.8 +/- 0.9 mV in 2 min. We speculate that the SHOC-induced initial depolarization of Vbl is a loss of Ba2(+)-sensitive K+ conductance caused by cell shrinkage. The subsequent repolarization/hyperpolarization of Vbl is caused by an enhanced basolateral membrane Na+ pump current and a reappearance of the Ba2(+)-sensitive K+ conductance. The parallel operation of Na(+)-H+ and Cl(-)-HCO3- exchanges will then supply Na+ for the pump current and, via cellular accumulation of Na+, K+, and Cl-, might result in a partial recovery of cell volume and thus Ba2(+) sensitive K+ conductance. PMID- 2106265 TI - Carbachol induces oscillations of membrane potassium conductance in a colonic cell line, T84. AB - Effects of carbachol on membrane potential and current in T84 cells were determined using whole cell patch-clamp techniques. When the pipettes contained a standard KCl solution and the bath contained a standard NaCl solution, carbachol (100 microM) caused a rapid hyperpolarization to the K+ equilibrium potential (EK+), followed by potential oscillations. When membrane potential was clamped to 0 mV, carbachol induced an outwardly directed K+ current in 31 of 37 cells, with a peak value of 618 +/- 51 (SE) pA. In 77% of these cells the current oscillated and gradually declined to base line. Atropine (20 microM) blocked this response. In symmetric KCl solutions the carbachol-induced current reversed at 0 mV with no rectification. Ba2+ or Cs+ did not block the current, but tetraethylammonium ion (TEA) reduced the number of responding cells. Although a Cl- conductance was found in resting cells, carbachol did not cause an increase in Cl- current when the cells were voltage-clamped to EK+, or when voltage-clamped to +/- 60 mV while bathed in symmetric NaCl solutions. When the Ca2(+)-buffering capacity of the pipette solution was increased, 80% of the cells responded to carbachol, but only 10% oscillated; however, no K+ current was induced by carbachol when the pipette was made nominally Ca2+ free. The current was not affected by removal of Ca2+ from the bath. These results show that carbachol induces an oscillating Ca2(+) activated K+ conductance in T84 cells, but no Cl- conductance. This K+ conductance is dependent on the mechanisms that regulate intracellular Ca2+. PMID- 2106266 TI - Glycogen phosphorylase in fish muscle: demonstration of three interconvertible forms. AB - White skeletal muscle of crucian carp contains a single isoenzyme of glycogen phosphorylase, which was purified approximately 300-fold to a specific activity of approximately 13 mumol.min-1.mg protein-1 (assayed in the direction of glycogen breakdown at 25 degrees C). Tissue extracts of crucian muscle produced three distinct peaks of phosphorylase activity when separated on DEAE-Sephacel. Peaks 1 and 3 were identified, in terms of kinetic properties and by interconversion experiments, as phosphorylase b and a, respectively. Peak 2 was shown to be a phospho-dephospho hybrid. The three interconvertible forms of phosphorylase were purified and shown to be dimeric molecules at 20 degrees C. At 5 degrees C, a and the hybrid tended to form tetramers. The Mr of the subunit was estimated to be 96,400 from sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The hybrid is kinetically homogeneous, and its kinetic properties are intermediate between those of b and a forms. The b, hybrid, and a forms of phosphorylase can be isolated from rapidly frozen muscle of crucian but in different proportions, depending on whether fish were anesthetized or forced to muscular activity for 20 s. Muscle of anesthetized crucian had 36, 36, and 28% of phosphorylase b, hybrid, and a forms, respectively, whereas the corresponding values for exercised fish were 12, 37, and 51%. Results suggest that three interconvertible forms of phosphorylase exist simultaneously in crucian muscle and that hybrid phosphorylase is active in contracting muscle in vivo. PMID- 2106267 TI - Amino acid metabolism after intense exercise. AB - We studied postexercise amino acid metabolism, in the whole body and across the forearm. Seven volunteers were infused with L-[alpha-15N]lysine and L-[1-13C] leucine twice [one time during 3 h after cycle exercise (75% VO2max), and one time in the resting state]. Whole body protein breakdown was estimated from dilution of L-[alpha-15N]lysine and L-[1-13C]ketoisocaproic acid (KIC) enrichments in plasma. Leucine oxidation was calculated from 13CO2 enrichments in expired air. Whole body protein breakdown was not increased above resting levels during the recovery period. Leucine oxidation was decreased after exercise (postexercise 13 +/- 2.3 vs. resting 19 +/- 3.2 mumol.kg-1.h-1; P less than 0.02), while nonoxidative leucine disposal was increased (115 +/- 6.1 vs. 103 +/- 5.6 micrograms.kg-1.min-1; P less than 0.02). After exercise, forearm net lysine balance was unchanged (87 +/- 25 vs. 93 +/- 28 nmol.100 ml-1.min-1), but there were decreases in forearm muscle protein degradation (219 +/- 51 vs. 356 +/- 85 nmol.100 ml-1.min-1; P less than 0.05) and synthesis (132 +/- 41 vs. 255 +/- 69 nmol.100 ml-1.min-1; P less than 0.01). In conclusion, after exercise 1) whole body protein degradation is not increased, 2) leucine disposal is directed away from oxidative and toward nonoxidative pathways, 3) forearm protein synthesis is decreased. Postexercise increases in whole body protein synthesis occur in tissues other than nonexercised muscle. PMID- 2106268 TI - Electrophysiological response to thyrotropin-releasing hormone of rat lactotrophs in primary culture. AB - The response of rat pituitary cells to thyrotropin-releasing hormone (TRH) in primary culture was studied in the whole-cell configuration with the patch-clamp technique. Prolactin (PRL)-containing cells were identified in the culture with a peroxidase-antiperoxidase immunocytochemical method. The cells were cultured from the pituitaries of diestrous (D) and lactating (L) female rats. Membrane electrophysiological properties (resting potential and input resistance) of pituitary cells in primary culture varied widely. Under the recording conditions reported here, the mean resting potential of lactotrophs was about -30 mV. There were spontaneous fluctuations in membrane resting potential (10-15 mV) as well as of membrane input resistance, making these parameters difficult to evaluate accurately. Most of the cells exhibited spontaneous firing activity that was shown to be mainly calcium-dependent. There was no difference between L and D cells in resting membrane electrophysiological properties. TRH (10(-7) M) induced a transient hyperpolarization of the membrane similar to that previously described in the GH3 clonal pituitary cell line. Voltage-clamp studies showed that this hyperpolarization resulted from activation of an outward current, the reversal potential of which ranged from -48 to -86.5 mV. Experimental manipulations of the ionic composition of internal and external recording media suggested that both K+ and Cl- were involved. This hyperpolarizing response was observed both in D and L cells, although L cells had larger and faster responses than D cells. This observation may be of physiological significance because lactotrophs have been reported to exist in various subtypes. PMID- 2106269 TI - Role of triglyceride-fatty acid cycle in controlling fat metabolism in humans during and after exercise. AB - We have investigated the role of triglyceride-fatty acid cycling in amplifying control of the net flux of fatty acids in response to exercise and in recovery from exercise. Five normal volunteers were infused with [1-13C]palmitate and D-5 glycerol throughout rest, 4 h of treadmill exercise at 40% maximum O2 consumption, and 2 h of recovery. Total fat oxidation was quantified by indirect calorimetry. Lipolysis (rate of appearance of glycerol) increased from 2.1 +/- 0.3 to 6.0 +/- 1.2 mumol.kg-1.min-1 after 30 min of exercise and progressively increased thereafter to a value of 10.5 +/- 0.8 mumol.kg-1.min-1 after 4 h. Lipolysis decreased rapidly during the first 20 min of recovery, but it was still significantly elevated after 2 h of recovery. The rate of appearance of free fatty acids followed the same pattern of response. Seventy percent of released fatty acids were reesterified at rest, and this value decreased to 25% within the first 30 min of exercise. Reesterification remained less than 35% of lipolysis until the start of recovery, at which time the value rose to 90%. In exercise, more than one-half the increase in fat oxidation could be attributed to the reduction in the percent reesterification. Most of the change in percent reesterification during exercise and recovery was caused by changes in extracellular cycling of fatty acids released into plasma. We conclude that triglyceride-fatty acid cycling plays an important role in enabling a rapid response of fatty acid metabolism to major changes in energy metabolism. PMID- 2106270 TI - Intestinal ornithine decarboxylase: half-life and regulation by putrescine. AB - Ornithine decarboxylase (ODC) is the primary rate-limiting enzyme for polyamine synthesis. ODC levels are increased in most tissues, including the intestinal mucosa, by growth-promoting agents. This enzyme has a brief half-life of from 5 to 30 min in mammalian tissues and is regulated by its product; putrescine. The current study examines the turnover and regulation of ODC in the mucosa of the small intestine. With the use of scraped intestinal mucosa from cycloheximide treated rats, the time course of the decline in ODC activity yielded a half-life of approximately 22 min. Labeling enzyme protein with [3H]difluoromethylornithine (DFMO) resulted in a nearly identical estimation of half-life. ODC activity of mucosa from isolated gut segments stimulated by luminal glycine (0.1-0.4 M) was enhanced 60-100% by 10 mM putrescine administered luminally. Putrescine alone had no effect on ODC. In contrast, 10(-7) M putrescine prevented 80% of the ODC activity stimulated by asparagine in IEC-6 cells (a rat intestinal crypt cell line). The half-life of ODC in unstimulated IEC-6 cells was 20 min and increased to 35 min in cells exposed to 10 mM asparagine. These data demonstrate that ODC of nonproliferating villous cells is regulated differently from the identical enzyme in proliferating crypt cells. Therefore, conclusions regarding mucosal growth should not be based totally on ODC activity from whole mucosa, since it is essentially a measure of only the enzyme present in the villous cells. PMID- 2106271 TI - Interaction of native and chemically modified albumin with pulmonary microvascular endothelium. AB - The ability of native and chemically modified bovine serum albumin (BSA) to maintain normal pulmonary microvascular permeability was tested in "bloodless," fluorocarbon emulsion exchange transfused rats. Wet-to-dry weight ratios (W/D) of whole lung and morphometric estimates of the amount of ferritin transported to basement membrane were used to assess changes in water flux and macromolecular transport, respectively. Native and modified BSA in capillary walls were localized by immunogold techniques. Arginine residues of BSA were blocked with cyclohexanedione (CHD-BSA), and lysine residues were modified either by succinylation (Succ-BSA) or reductive methylation. Succinylation and CHD modification of BSA caused alterations in antigenicity and trypsin sensitivity; succinylation reduced the isoelectric point (pI). Whereas administration of either CHD-BSA or Succ-BSA increased the W/D, transport of ferritin to basement membrane was greater in the presence of Succ-BSA than CHD-BSA. By contrast, infusion of reductively methylated BSA in which modified lysines altered neither antigenicity nor pI, resulted in a W/D and amount of ferritin in basement membranes comparable to that of BSA. Binding of CHD-BSA and Succ-BSA to endothelial glycocalyx appeared to be reduced relative to native BSA and reductively methlyated BSA. The lowered pI of Succ-BSA may have contributed to its reduced binding; reductively methylated BSA with an unaltered pI was present in the glycocalyx. These data are consistent with a role for positively charged arginine residues in the interaction of albumin with the glycocalyx. The W/D of animals perfused with BSA was higher than those reported for rats perfused with complete rat serum proteins. This is consistent with the notion that serum factors, in addition to albumin, are required to maintain normal microvascular permeability. PMID- 2106272 TI - Splenic pathology in thrombotic thrombocytopenic purpura. AB - To determine splenic pathology in thrombotic thrombocytopenic purpura (TTP), 10 spleens and two accessory spleens were studied. The eight women and two men ranged from 20 to 66 years of age (mean age, 39 years). Three spleens were enlarged. Thrombi were noted in arteries and arterioles in nine specimens: no associated inflammation was seen. Periodic acid-Schiff-positive diastase resistant hyaline subendothelial deposits (SEDs) were present in all cases. Some arterioles showed a transition between thrombi and SEDs. The presence of platelets or platelet-related material in SEDs and thrombi was documented by factor VIII staining. Hyperplasia of B cells and germinal centers was present in 67%, and periarteriolar concentric fibrosis ("onion-skinning") in 58%. Histiocytes showed prominent iron deposits in 92% and hemophagocytosis in 83% of cases. Extramedullary hematopoiesis was present in 42%. Blood lakes, infarcts, and endothelial hyperplasia were rarely noted; microaneurysms were not seen. Ten spleens from patients with idiopathic thrombocytopenic purpura and 10 age-matched control spleens rarely showed SEDs or hemosiderosis and did not show hemophagocytosis or thrombi. We conclude that subendothelial deposits may be related to platelet thrombi incorporated into vessel walls. Germinal centers and periarteriolar concentric fibrosis may indicate an immunologic role in TTP, as in systemic lupus erythematosus. PMID- 2106273 TI - Nutritional support in surgical practice: Part I. AB - Critical evaluation of the therapeutic benefit gained from provision of nutritional support requires knowledge regarding the nutritional status of those to whom it was given. The apparent effect of giving parenteral nutrition or enteral nutrition depends not only on how much and how well it is given, but also on how depleted the recipient is. Thus, nutritional assessment requires close examination before proceeding to assess the efficacy and potential benefits of the remedial measures of parenteral nutrition or enteral nutrition. Although preoperative malnutrition is associated with a poor operative outcome, there appears to be no consensus as to whether perioperative nutritional support can reduce postoperative complications to the level occurring in well-nourished patients undergoing similar procedures. This is partly because reports evaluating the effect of perioperative nutritional support on postoperative outcome vary widely as to numbers of patients studied, primary diagnoses, and the duration and quality of perioperative nutritional support. In Part I, these issues are explored in patients who are undergoing operations for cancer, trauma, or burns. Enteral nutrition appears to be as effective as parenteral nutrition in improving operative outcome, as compared with ad libitum oral nutrition. Postoperative enteral nutrition and parenteral nutrition are equally effective in reducing postoperative complications. PMID- 2106274 TI - [Antagonism of flunitrazepam and fentanyl by flumazenil, naloxone or nalbuphine]. AB - The new benzodiazepine antagonist flumazenil represents another approach to the ever-present problem of recurring respiratory depression after anesthesia with flunitrazepam and fentanyl. Objective and subjective side effects of flumazenil were studied in comparison with the opiate antagonists naloxone and nalbuphine. METHODS. One hundred fifty surgical patients, ASA I or II, aged 18-65 years were studied. After premedication with atropine 0.5 mg and flunitrazepam 0.5 mg anesthesia was induced with flunitrazepam 0.5 mg, fentanyl 0.1 mg and etomidate 10 mg and maintained with N2O/O2 2:1 and additional increments of 0.1 mg fentanyl as required. Relaxation for intubation and surgery was obtained with non depolarizing muscle relaxants. After the operation the patients were extubated and then flumazenil 0.4 mg, naloxone 0.05 mg, or nalbuphine 20 mg was given i.v. (randomized and double-blind). In 15 patients blood pressure and heart rate were monitored. In all patients postoperative pain was assessed by the time interval between administration of the antagonist and need for the first analgesic medication. On the 1st postoperative day recall of postoperative events and of pictures shown 5, 30, 60, 120, and 240 min after administration of the antagonist was tested. The patients were interviewed a second time for side effects on day 3 6 after the operation. RESULTS. The three antagonists produced no significant effects on arterial pressure and heart rate. There were no differences between the antagonists in the incidence of postoperative nausea and/or vomiting or postoperative pain. After flumazenil, a significant transient increase in vigilance and better recall of postoperative events was noted within 5 and 30 min after administration of the drug. CONCLUSION. On the basis of the objective clinical findings, there is no reason to prefer either benzodiazepine or opiate antagonists after flunitrazepam and fentanyl. However, postoperative amnesia can be reduced by flumazenil if this is desirable. PMID- 2106275 TI - [Early recognition of malignant hyperthermia using capnometry]. AB - Although malignant hyperthermia is still a potentially fatal disease that was marked by a high mortality until recently, lasting damage to the patient can now be prevented by early diagnosis and treatment. The following case demonstrates the special value of capnometry in diagnosing this condition. A 34-year-old man admitted for oral surgery showed symptoms of malignant hyperthermia 5 h after induction of anesthesia. Neuroleptanalgesia had been conducted. The patient had received thiopental and fentanyl for induction of anesthesia and alcuronium and succinylcholine for intubation. The first symptom noticed was an elevation of the end-tidal pCO2 as monitored by capnometry. Additional symptoms, such as a pronounced rise in temperature, blood pressure, and heart rate did not develop until 20-25 min later. The end-tidal oxygen concentration decreased from 30 vol. % to 26 vol.-%. The patient had to be ventilated with a volume of 25 l/min to keep end-tidal pCO2 under 6 kPa. Treatment with dantrolene was started immediately. Not until 3 h after the onset of the first symptoms did the patient's body temperature and the minute volume needed for ventilation return to normal. Postoperative laboratory findings showed only a slight elevation of creatine kinase and serum lactate. Myoglobin was not detected in serum or urine. This case indicates that capnometry permitted immediate adaptation of controlled ventilation to the patient's increased metabolic rate and early initiation of dantrolene treatment, thus preventing more severe disorders and possible consequences for the patient. Other studies have also suggested the special importance of capnometry. Since the patient refused to give his consent, the diagnosis could not be ascertained by muscle biopsy, and had to be based on symptoms. PMID- 2106276 TI - [A successful lytic treatment of a perioperative pulmonary embolism necessitating resuscitation using recombinant tissue-type plasminogen activator]. AB - We report a patient with massive perioperative pulmonary embolism (stage IV) and cardiac arrest who was successfully treated with recombinant tissue plasminogen activator (rt-PA). Thrombolytic therapy was started with 25 mg rt-Pa over 15 min followed by another 25 mg over 45 min. During the next 5 h 50 mg were infused, and thereafter an additional 50 mg over 24 h. No major alterations in the plasmatic coagulation profile were noted. With the exception of moderate blood loss from one puncture site, no further bleeding complications occurred. The relevance of this new thrombolytic agent in the perioperative management of acute, life-threatening pulmonary embolism is discussed. PMID- 2106277 TI - Comparison between bronchial response to inhaled hypoosmolar and isoosmolar solutions of sodium cromoglycate after exercise challenge. AB - The effectiveness of a sodium cromoglycate isoosmolar solution (288 mOsmol/L) versus hypoosmolar commercial solution (40 mOsmol/L) was studied in 14 asthmatic children with exercise-induced asthma. The mean FEV1 after exercise in patients pretreated with a sodium cromoglycate hypotonic solution compared with FEV1 at rest was -2% +/- 10%. The mean FEV1 after exercise in patients pretreated with an isotonic solution compared with FEV1 at rest was 3% +/- 6%. This statistically significant difference (P less than .01) proves that the effectiveness of sodium cromoglycate can be improved by raising the osmolarity to isotonic levels. PMID- 2106278 TI - Treatment with gammaglobulin preparation for intravenous use in children with humoral immunodeficiency: clinical and immunologic follow-up. AB - We have treated 23 children aged 6 to 15 years affected with agammaglobulinemia or severe hypogammaglobulinemia with IgG serum levels less than 100 mg/dL with IV gammaglobulin (Sandoglobulin), 150 to 300 mg/kg/3 wk for more than 3 years. The children suffered from severe and recurrent bacterial infections, mainly of the respiratory tract. They had been treated previously with IM gammaglobulin (0.8 ml/kg/3 wk), but their serum IgG values were never higher than 100 mg/dL. We compared the data of the follow-up after 3 years of treatment with IV gammaglobulin and the follow-up after 2 years course of IM gammaglobulin. Minor adverse reactions (chills, fever, abdominal pain) were observed only in some children during the first months of therapy. These data demonstrate that the number of infections or days with fever, in bed, or in hospital dramatically decreased during IV Ig therapy, while IgG serum levels increased to approximately normal values. IV Ig is a safe and effective treatment for patients with humoral immunodeficiency. PMID- 2106279 TI - Combined effect of inhaled verapamil and sodium cromoglycate on the airway response to hypertonic saline. AB - We evaluated the airway effect of inhaled verapamil by comparing it to aerosolized sodium cromoglycate. Airway hyperreactivity was assessed using inhaled hypertonic saline. Sodium cromoglycate prevented bronchoconstriction in all the patients. Inhaled verapamil induced significant bronchial constriction in two patients. The combination of verapamil with sodium cromoglycate was as effective as sodium cromoglycate. It was concluded that inhaled verapamil is not effective in preventing bronchoconstriction induced by hypertonic saline. PMID- 2106280 TI - [Assay of sex hormone-binding globulin (SHBG) in human serum. Comparative measurements using three methods]. AB - Determination of sex-hormone-binding-globulin was performed by three methods: binding, electroimmunodiffusion and DELFIA methods. Results of normal and pathological values correlated well with the three techniques. PMID- 2106281 TI - High prevalence of antibody to hepatitis C virus in multitransfused hemophiliacs with normal transaminase levels. PMID- 2106282 TI - Misoprostol, diarrhea, and psyllium mucilloid. PMID- 2106283 TI - Microbial degradation of quinoline and methylquinolines. AB - Several bacterial cultures were isolated that are able to degrade quinoline and to transform or to degrade methylquinolines. The degradation of quinoline by strains of Pseudomonas aeruginosa QP and P. putida QP produced hydroxyquinolines, a transient pink compound, and other undetermined products. The quinoline degrading strains of P. aeruginosa QP and P. putida QP hydroxylated a limited number of methylquinolines but could not degrade them, nor could they transform 2 methylquinoline, isoquinoline, or pyridine. Another pseudomonad, Pseudomonas sp. strain MQP, was isolated that could degrade 2-methylquinoline. P. aeruginosa QP was able to degrade or to transform quinoline and a few methylquinolines in a complex heterocyclic nitrogen-containing fraction of a shale oil. All of the quinoline- and methylquinoline-degrading strains have multiple plasmids including a common 250-kilobase plasmid. The 225-, 250-, and 320-kilobase plasmids of the P. aeruginosa QP strain all contained genes involved in quinoline metabolism. PMID- 2106284 TI - Effects of growth temperature and strictly anaerobic recovery on the survival of Listeria monocytogenes during pasteurization. AB - Listeria monocytogenes F5069 was suspended in either Trypticase soy broth-0.6% yeast extract (TSBYE) or sterile, whole milk and heated at 62.8 degrees C in sealed thermal death time tubes. Severely heat-injured cells were recovered in TSBYE within sealed thermal death time tubes because of the formation of reduced conditions in the depths of the TSBYE. Also, the use of strictly anaerobic Hungate techniques significantly increased recovery in TSBYE containing 1.5% agar compared with aerobically incubated controls. The exogenous addition of catalase, but not superoxide dismutase, slightly increased the recovery of heat-injured cells in TSBYE containing 1.5% agar incubated aerobically. Growth of cells at 43 degrees C caused a greater increase in heat resistance as compared with cells heat shocked at 43 degrees C or cells grown at lower temperatures. Growth of L. monocytogenes at 43 degrees C and enumeration by the use of strictly anaerobic Hungate techniques resulted in D62.8 degrees C values that were at least sixfold greater than those previously obtained by using cells grown at 37 degrees C and aerobic plating. Results indicate that, under the conditions of the present study, high levels of L. monocytogenes would survive the minimum low-temperature, long-time treatment required by the U.S. Food and Drug Administration for pasteurizing milk. The possible survival of low levels of L. monocytogenes during high-temperature, short-time pasteurization and enumeration of injured cells by recovery on selective media under strictly anaerobic conditions are discussed. PMID- 2106285 TI - Efficacy of a variety of disinfectants against Listeria spp. AB - The efficacy of 14 disinfectants against Listeria innocua and two strains of Listeria monocytogenes in the presence of organic matter was studied. Quantitative efficacy tests were used. Many of the disinfectants tested were not as effective on Listeria spp. when the test organisms were dried onto the surface of steel disks (carrier tests) as they were when the organisms were placed in suspension (suspension test). The presence of whole serum and milk (2% fat) further reduced the disinfectant capacities of most of the formulations studied. Only three disinfectants (povidone-iodine, chlorhexidine gluconate, and glutaraldehyde) were effective in the carrier test in the presence of serum; however, all three were ineffective when challenged with milk (2% fat). Only one solution, sodium dichloroisocyanurate, was effective in the presence of milk. All but four formulations (chloramine-T, phosphoric acid, an iodophor, and formaldehyde) were effective in the suspension tests, regardless of the organic load. L. monocytogenes was observed to be slightly more resistant to disinfection than L. innocua was. There was no difference in disinfectant susceptibility between the two strains of L. monocytogenes. These findings emphasize the need for caution in selecting an appropriate disinfectant for use on contaminated surfaces, particularly in the presence of organic material. PMID- 2106286 TI - Transport of a genetically engineered Pseudomonas fluorescens strain through a soil microcosm. AB - Vertical soil microcosms flushed with groundwater were used to study the influence of water movement on survival and transport of a genetically engineered Pseudomonas fluorescens C5t strain through a loamy sand and a loam soil. Transport of cells introduced into the top 1 cm of the vertical soil microcosms was dependent on the flow rate of water and the number of times microcosms were flushed with groundwater. The presence of wheat roots growing downward in the microcosms contributed only slightly to the movement of P. fluorescens C5t cells to lower soil regions of the loamy sand microcosms, but enhanced downward transport in the loam microcosms. Furthermore, the introduced P. fluorescens C5t cells were detected in the effluent water samples even after three flushes of groundwater and 10 days of incubation. As evidenced by a comparison of counts from immunofluorescence and selective plating, nonculturable C5t cells occurred in day 10 soil and percolated water samples, primarily of the loamy sand microcosms. Vertical soil microcosms that use water movement may be useful in studying the survival and transport of genetically engineered bacteria in soil under a variety of conditions prior to field testing. PMID- 2106287 TI - Vapor-phase hydrogen peroxide as a surface decontaminant and sterilant. AB - The feasibility of utilizing vapor-phase hydrogen peroxide (VPHP) as a surface decontaminant and sterilant was evaluated in a centrifuge application. The prototype VPHP decontamination system, retrofitted into a Beckman L8-M ultracentrifuge, was designed to vaporize a 30% (wt/wt) solution of aqueous hydrogen peroxide continuously injecting and withdrawing VPHP in a deep-vacuum flow-through system. VPHP cycles of 4, 8, 16, and 32 min were examined for cidal activity against spores of Bacillus subtilis subsp. globigii and Bacillus stearothermophilus. Spore inocula (approximately 10(6)/coupon) were dried onto 0.5-in. (1.27-cm)-square stainless-steel coupons, and coupons were suspended in the centrifuge chamber, the space between the refrigeration can and the barrier ring (inner gap), and the space between the barrier ring and the vacuum ring (outer gap). At a chamber temperature of 4 degrees C, B. subtilis subsp. globigii spores were inactivated within 8 min, while inactivation of spores located in the outer gap at 27 degrees C required 32 min. The elevated temperature and high surface area/volume ratios in the outer gap may serve to decompose the gas more rapidly, thus reducing cidal efficacy. Of the two test spores, B. stearothermophilus was more resistant to VPHP. Nonetheless, VPHP was shown to possess significant sporicidal capability. For practical decontamination applications of the type described, VPHP shows promise as an effective and safer alternative to currently used ethylene oxide or formaldehyde vapors. PMID- 2106288 TI - Phosphorylase and creatine kinase modification by thiol-disulfide exchange and by xanthine oxidase-initiated S-thiolation. AB - The reaction of glycogen phosphorylase b and creatine kinase with glutathione disulfide, cystine, and cystamine was compared by direct analysis on electrofocusing gels. This method was useful for individual proteins or for mixtures of the proteins. Millimolar concentrations of glutathione disulfide were required for both proteins and the rate of modification of each protein was similar. The reaction of glutathione disulfide with creatine kinase was inhibited by reduced glutathione (GSH), but the effect on the reaction with phosphorylase was minimal. Cystine and cystamine were required in micromolar amounts to effectively form the disulfide adducts. Both proteins were modified by cystine but cystamine reacted only with phosphorylase. Cystamine (10 microM) was an effective inhibitor of the reaction of phosphorylase b with 2 mM glutathione disulfide. S-thiolation of creatine kinase inactivated the enzyme and a direct assay of the enzyme activity could be used to quantitate S-thiolation of this protein by each of the disulfides. The effect of each disulfide on enzyme activity confirmed the results obtained by gel electrofocusing. Glutathione disulfide and cystine both inactivated the enzyme while cystamine had no effect on the activity. S-thiolation of phosphorylase had no observable effect on any activity parameter, but it effectively prevented binding of phosphorylase to high molecular-weight glycogen, probably at the glycogen storage site of phosphorylase. The rate of S-thiolation of a mixture of phosphorylase and creatine kinase by thiol-disulfide exchange with glutathione disulfide was compared to the rate of S-thiolation of these proteins by a xanthine oxidase initiated process (presumably due to protein sulfhydryl activation by reactive oxygen species). The xanthine oxidase-initiated mechanism was somewhat faster than thiol-disulfide exchange with both proteins. It was shown that GSH inhibited S-thiolation of creatine kinase by this mechanism as well as by thiol-disulfide exchange. It is suggested that both mechanisms may play a role in protein S thiolation in vivo. For proteins that are typified by creatine kinase, the concentration of GSH in the cells may determine whether the S-thiolated form of the protein accumulates. For proteins typified by phosphorylase b, the accumulation of S-thiolated forms may be more independent of GSH. PMID- 2106289 TI - Characteristics of a thrombin inhibitor secreted by activated platelets. AB - A 77-kDa complex of thrombin and a protein secreted by activated platelets had little if any thrombin amidolytic activity, indicating that the secreted protein is an inhibitor. The molecular weight of the inhibitor before reaction with thrombin was approximately 50,000. The apparent second-order rate constant for complex formation was estimated to be 1.3 x 10(6) M-1 s-1 (mean of four measurements); it was not affected by heparin or heparinase. These properties distinguish this inhibitor from other protease inhibitors secreted by platelets. The inhibitor reacted with trypsin and possibly with urokinase but not with factor Xa. PMID- 2106290 TI - Insulin increases the synthesis of phospholipid and diacylglycerol and protein kinase C activity in rat hepatocytes. AB - The effects of insulin on phospholipid metabolism and generation of diacylglycerol (DAG) and on activation of protein kinase C in rat hepatocytes were compared to those of vasopressin and angiotension II. Insulin provoked increases in [3H]glycerol labeling of phosphatidic acid (PA), diacylglycerol (DAG), and other glycerolipids within 30 s of stimulation. Similar increases were also noted for vasopressin and angiotensin II. Corresponding rapid increases in DAG mass also occurred with all three hormones. As increases in [3H]DAG (and DAG mass) occurred within 30-60 s of the simultaneous addition of [3H]glycerol and hormone, it appeared that DAG was increased, at least partly, through the de novo synthesis of PA. That de novo synthesis of PA was increased is supported by the fact that [3H]glycerol labeling of total glycerolipids was increased by all three agents. Increases in [3H]glycerol labeling of lipids by insulin were not due to increased labeling of glycerol 3-phosphate, and were therefore probably due to activation of glycerol-3-phosphate acyltransferase. Unlike vasopressin, insulin did not increase the hydrolysis of inositol phospholipids. Insulin- and vasopressin-induced increases in DAG were accompanied by increases in cytosolic and membrane-associated protein kinase C activity. These findings suggest that insulin-induced increases in DAG may lead to increases in protein kinase C activity, and may explain some of the insulin-like effects of phorbol esters and vasopressin on hepatocyte metabolism. PMID- 2106291 TI - Reconstitution of testosterone oxidation by purified rat cytochrome P450p (IIIA1). AB - Cytochrome P450p (IIIA1) has been purified from rat liver microsomes by several investigators, but in all cases the purified protein, in contrast to other P450 enzymes, has not been catalytically active when reconstituted with NADPH cytochrome P450 reductase and dilauroylphosphatidylcholine. We now report the successful reconstitution of testosterone oxidation by cytochrome P450p, which was purified from liver microsomes from troleandomycin-treated rats. The rate of testosterone oxidation was greatest when purified cytochrome P450p (50 pmol/ml) was reconstituted with a fivefold molar excess of NADPH-cytochrome P450 reductase, an equimolar amount of cytochrome b5, 200 micrograms/ml of a chloroform/methanol extract of microsomal lipid (which could not be substituted with dilauroylphosphatidylcholine), and the nonionic detergent, Emulgen 911 (50 micrograms/ml). Testosterone oxidation by cytochrome P450p was optimal at 200 mM potassium phosphate, pH 7.25. In addition to their final concentration, the order of addition of these components was found to influence the catalytic activity of cytochrome P450p. Under these experimental conditions, purified cytochrome P450p converted testosterone to four major and four minor metabolites at an overall rate of 18 nmol/nmol P450p/min (which is comparable to the rate of testosterone oxidation catalyzed by other purified forms of rat liver cytochrome P450). The four major metabolites were 6 beta-hydroxytestosterone (51%), 2 beta hydroxytestosterone (18%), 15 beta-hydroxytestosterone (11%) and 6 dehydrotestosterone (10%). The four minor metabolites were 18-hydroxytestosterone (3%), 1 beta-hydroxytestosterone (3%), 16 beta-hydroxytestosterone (2%), and androstenedione (2%). With the exception of 16 beta-hydroxytestosterone and androstenedione, the conversion of testosterone to each of these metabolites was inhibited greater than 85% when liver microsomes from various sources were incubated with rabbit polyclonal antibody against cytochrome P450p. This antibody, which recognized two electrophoretically distinct proteins in liver microsomes from troleandomycin-treated rats, did not inhibit testosterone oxidation by cytochromes P450a, P450b, P450h, or P450m. The catalytic turnover of microsomal cytochrome P450p was estimated from the increase in testosterone oxidation and the apparent increase in cytochrome P450 concentration following treatment of liver microsomes from troleandomycin- or erythromycin-induced rats with potassium ferricyanide (which dissociates the cytochrome P450p-inducer complex). Based on this estimate, the catalytic turnover values for purified, reconstituted cytochrome P450p were 4.2 to 4.6 times greater than the rate catalyzed by microsomal cytochrome P450p. PMID- 2106292 TI - Age-related change in the degradation rate of ovalbumin microinjected into mouse liver parenchymal cells. AB - Change in the degradation rate of ovalbumin (OVA) microinjected into liver parenchymal cells isolated from mice of various ages was studied. OVA was injected by osmotic lysis of pinosomes and the amount of OVA was determined by immunoblotting using purified antibody to OVA. Cellular activity as judged by rates of protein synthesis and degradation of pulse-labeled proteins was not affected by the injection. To localize injected OVA in the cells, cell extracts were fractionated by differential centrifugation and the amount of OVA and the activity of beta-D-galactosidase as a lysosomal marker enzyme of each fraction were determined. The ovalbumin was mostly found in the soluble fraction, while the beta-D-galactosidase activity was found in the particulate fraction, indicating that the ovalbumin was spread in the cytosol but was not present in the pinosomes or lysosomes. The average half-lives of OVA were 106, 113, and 164 h in the cells from young (3.5-6.5 months), middle-aged (13.5-20.0 months), and old (24.5-30.5 months) mice, respectively. Thus, the half-life of ovalbumin in the cells of senescent mice was about 50% longer than that in the cells of young or middle-aged mice. These results are in good agreement with those of our previous investigation, which showed that the half-life of inactivation of horseradish peroxidase was extended by about 50% in the hepatocytes from old mice (Ishigami and Goto, 1988, Mech. Ageing Dev., 46, 125-133). PMID- 2106293 TI - Enzymatic formation of 9,16-dihydro(pero)xyoctadecatrienoic acid isomers from alpha-linolenic acid. AB - Incubation of alpha-linolenic acid with soybean lipoxygenase at pH 6.5 led to formation of conjugated triene oxidation products exhibiting maximum uv absorption at 267 nm, which were converted into four 9,16 dihydroxyoctadecatrienoic acid isomers. In the precursor-substrate study, it seems that 9,16-dihydroxy acid isomers are derived from the doubly oxygenated products and the epoxide intermediate, which are both produced from hydrogen removal at C-14 of 9(S)-hydroperoxyoctadecatrienoic acid. Optimum pH and Km values for soybean lipoxygenase-1-catalyzed conversion of 9(S) hydroperoxyoctadecatrienoic acid into the conjugated triene products were 8.5 and 80 microM, respectively. PMID- 2106294 TI - Vascular properties of canine lungs perfused with Eurocollins solution and prostacyclin. AB - Although Eurocollins solution (ECS) is commonly used for lung preservation, its vascular effects and their time course and response to pharmacological interventions are not well understood. The effect of 4 degrees C ECS on the pulmonary circulation was assessed in excised canine left lower lobes. The roles of static oxygen inflation and prostacyclin infusion during ECS perfusion were also examined. The lobes were divided into five groups: time control (A), ECS with oxygen (B), ECS without oxygen (C), ECS with glycine buffer (D), and ECS with prostacyclin (E); group D was the control for E. Eurocollins solution had no effect on gas exchange but had a marked effect on the pulmonary circulation. Vascular conductance decreased from 22.6 to 18.9 mL/min/cm H2O and from 21.3 to 14.1 mL/min/cm H2O with average vascular closure increasing by 1.2 and 2.1 cm H2O in groups B and C, respectively. The decreased vascular conductance and increased vascular closure was associated with a reduction in vascular compliance from 1.63 to 1.25 mL/cm H2O. When prostacyclin was added to ECS, the reduction in vascular closure was much less and was associated with a decrease in vascular closure and no loss of vascular compliance. Eurocollins solution increases pressure cost for perfusion by causing both vascular obstruction and increased tone, especially when oxygen is not provided. This is significantly overcome by addition of prostacyclin infusion during ECS perfusion. PMID- 2106295 TI - Surgical ablation for idiopathic ventricular tachycardia. AB - A 33-year-old man with a right-bundle branch, left-axis deviation ventricular tachycardia was medically treated unsuccessfully. Surgical mapping and ablation was performed with a successful surgical result. A discussion of surgical results for this problem is provided. PMID- 2106296 TI - [Infected false aneurysm at the level of an aortotomy cicatrix 5 years after mechanical replacement of the aortic valve]. AB - The authors report the case of Streptococcus Bovis Infection of a pseudoaneurysm which developed in the aortotomy suture line five years after aortic valve replacement with a Bjork-Shiley prosthesis. This was an isolated lesion without involvement of the prosthesis or aortic ring and was an operative finding. PMID- 2106297 TI - [Carotid artery thrombosis and myocardial infarction in nephrotic syndrome]. AB - The authors report the case of a 18 year old man with a chronic corticosteroid refractory nephrotic syndrome complicated by carotid artery thrombosis and myocardial infarction. Thromboembolism is one of the most serious complications of the nephrotic syndrome. Serious clotting factor disturbances are observed: changes in platelet function (hyperaggregability) increased plasma zymogens and cofactors, increased plasma fibrinogen, abnormalities of the fibrinolytic system and acquired deficiencies of coagulation inhibitors. The respective role of each of these abnormalities have not been clearly established, but it is likely that increased platelet aggregation and antithrombin III deficiency are important factors in producing a hypercoagulable state in the nephrotic syndrome. Hyperlipidemia is also a characteristic feature of the nephrotic syndrome: these is a wide spectrum of lipoprotein patterns with increased low density lipoproteins (LDL) or very low density lipoproteins (VLDL) or both; contradictory results have been reported with respect to the high density lipoproteins (HDL): decreased, normal or even increased plasma levels have been observed. In addition, changes in the distribution and composition of LDL and VLDL subclasses have been detected. Most of these changes have an atherogenic potential but controversy still surrounds the question of the prevalence of ischaemic heart disease in the nephrotic syndrome; it is unlikely that nephrotic syndromes of short duration have any influence on the incidence of coronary events, but patients with chronic heavy protein urea and long-term exposure to abnormalities of haemostasis and lipid profiles appear to have a significant risk of developing cardiovascular disease and may require long-term anticoagulant therapy. PMID- 2106298 TI - [Successful cardiac transplantation after 38 days of circulatory assistance with a heterotopic artificial heart]. AB - The survival of a patient with irreversible cardiac failure on the cardiac transplantation waiting list was assured for 38 days by circulatory assistance with heterotopic Pierce Donachy prosthetic ventricles and followed by successful cardiac transplantation. This method of circulatory assistance is relatively simple to install from the technical point of view and provides a satisfactory haemodynamic result whilst waiting for a compatible donor organ. Several complications, some of them serious, were observed. Some were related to the patient's poor preoperative condition: acute renal failure, disorders of coagulation. These regressed slowly when the patient's haemodynamic status improved. On the other hand, septic problems and local haemorrhage were inherent to this technique. These are the commonest complications reported by other authors. Although the mortality rate during the period of circulatory assistance may appear to be high, this technique remains a valuable method of survival for selected patients and does not affect the chances of success of ulterior cardiac transplantation. PMID- 2106299 TI - [Treatment of massive arterial thrombosis caused by thrombocytopenia induced by heparin with local thrombolysis]. AB - The authors report the case of a patient treated by subcutaneous injection of calcium heparin after deep vein thrombosis with floating thrombus and pulmonary embolism. She was readmitted to hospital after 16 days' treatment because of a massive aorto-iliac thrombosis due to heparin-induced thrombocytopenia (platelet count = 29.000). This thrombosis was treated by local injection of Urokinase (total dose = 7.425.000 U) over 93 hours without any major complications. The aorto-iliac circulation was completely restored to normal after treatment. Thrombotic complications secondary to immuno-allergic heparin-induced thrombocytopenia are relatively common because of the widespread use of heparin. From the therapeutic point of view, it is imperative to stop the heparin, which makes surgery very difficult, and the platelet-fibrin composition of these thrombi suggests that local thrombolysis with Urokinase is the treatment of choice in this syndrome. PMID- 2106300 TI - [Association of cutaneous myxoma, recurrent cardiac myxoma and Cushing's syndrome (Carney's complex). Description of a case and review of the literature]. AB - The authors report the case of a rare clinical syndrome which has recently been called Carney's complex or "myxomas, spotty pigmentation and endocrine overactivity". Three components of this complex are described: cutaneous myxomas, Cushing's syndrome of unpredictable evolution treated by bilateral adrenalectomy for multiple adrenal adenoma and left atrial myxoma which recurred twice. The authors review the literature and discuss the practical implications of this new syndrome which may be familial. The role of echocardiography, the key investigation for the detection of the myxoma and follow-up of these patients who have a high risk of recurrence, is underlined. PMID- 2106301 TI - [Effect of cardioversion of atrial fibrillation on left ventricular function in dilated cardiomyopathy. A multicenter study]. AB - A group of 73 patients with idiopathic dilated cardiomyopathy were followed up for an average of 22 +/- 7 months to assess the medium term evolution of echocardiographic parameters of left ventricular function and, in particular, the consequences of cardioversion of atrial fibrillation. Seventy nine per cent of patients presented with cardiac failure. Left bundle branch block was observed in 20% and ventricular arrhythmias were frequent in 31%, complex in 62% with episodes of non-sustained ventricular tachycardia in 10% of cases. Left ventricular dilatation was greater in patients with complete left bundle branch block (p less than 0.003). Atrial fibrillation was present in 14 patients (19%) who were generally older than the rest of the study population (p less than 0.02) and was associated with less severe left ventricular dysfunction (p less than 0.01). Return to sinus rhythm was obtained in 9 patients. Echocardiographic data was obtained in 64 patients after an average of 6.2 +/- 1.7 months. Left ventricular function improved during the follow-up period and returned to normal in 12% of cases. Reduction of atrial fibrillation to sinus rhythm was the only predictive factor of normalisation of left ventricular function (p less than 0.02). The changes in left ventricular end diastolic dimension and fractional shortening was less marked in the group of 56 patients in sinus rhythm or chronic atrial fibrillation (normalisation of left ventricular function in 8% of cases) than in the group of 8 patients in which atrial fibrillation was converted to sinus rhythm (normalisation of left ventricular function in 50% of cases).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106302 TI - [Value of transesophageal echocardiography. From a preliminary experience of 532 cases]. AB - Transesophageal echocardiography (TEE) was introduced recently in France. The aim of this study was to review the diagnostic value of this technique after 8 months' use in our cardiology department. A total of 532 TEE studies were carried out between April and December 1988 in 396 patients (average age 54 years, range 17 to 89 years) at Tenon Hospital. The failure rate was 1.8 per cent (N = 10), over half of which occurred at the beginning of the operator's experience. TEE was particularly valuable compared with the standard transthoracic approach in the following instances: the investigation of mitral stenosis, especially before percutaneous valvuloplasty (N = 75). A left atrial thrombus was demonstrated in 5 cases by TEE vs none by standard echocardiography. There was also a much higher diagnostic sensitivity for small interatrial shunts (40 vs 6) resulting from transseptal catheterisation. In the preoperative investigation of severe mitral regurgitation (N = 29). The etiology was accurately diagnosed in 29 vs 26 cases, and the mechanism of the regurgitation was correctly classified especially in cases of ruptured chordae (15 vs 6 cases). In endocarditis (N = 26) by the visualisation of abscess of the aortic ring (7 vs 1) and vegetations (19 vs 8). In prosthetic valve dysfunction (N = 65) by the demonstration of primary degeneration of bioprostheses (7 vs 4), perivalvular leaks (10 vs 4) and non occlusive thrombi of mechanical prostheses (3 vs 0). In cases of intracardiac tumours, dissection of the thoracic aorta and atrial septal defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106303 TI - [Frequency of the onset of supraventricular tachyarrhythmias as a function of underlying heart disease]. AB - The prevalence of inducible ventricular arrhythmias is related to the underlying pathology. This study was undertaken to determine the prevalence of supraventricular tachyarrhythmias (SVT), atrial tachycardia, flutter or fibrillation, sustained for over 30 seconds. Programmed atrial stimulation was used to deliver 1 or 2 extrastimuli during sinus and paced rhythm in 230 subjects without obvious cardiac disease (149 without and 81 with spontaneous SVT) and 432 patients with documented cardiac pathology (407 without and 25 with spontaneous SVT). The incidence of inducible SVT with respect to that of spontaneous SVT and in relation to cardiac pathology was as follows: (table; see text) The prevalence of inducible SVT in patients without spontaneous SVT was related to the type of pathology: (table; see text) These results show that in patients with spontaneous SVT the induction of the arrhythmia was facilitated by the presence of underlying cardiac pathology (sensitivity increasing from 67% to 88%). In patients without spontaneous SVT, the nature of the underlying disease was related to the prevalence of inducible SVT, the risk being major in SA block, right ventricular dysplasia and mitral valve prolapse (60-80%) and moderate in dilated CMP and myocardial infarction (35 to 40%). PMID- 2106304 TI - [Factors influencing survival after surgery of pure non-ischemic mitral insufficiency]. AB - Uni and multifactorial (Cox) statistical analysis of the results of surgery in a series of 247 patients operated between 1969 and 1988 for pure, non-ischaemic mitral regurgitation was undertaken to determine the factors influencing operative and late mortality. All but 3 cases were adults, average age 51 years, and very symptomatic (75 per cent Class III et IV of NYHA Classification). Dystrophic or degenerative lesions were responsible for 53 per cent of cases of regurgitation whilst rheumatic valvular disease was only observed in 30 per cent of cases. Mitral valve replacement was performed in 137 patients (96 mechanical and 41 bioprostheses) and conservative surgery was possible in 110 cases. There were 12 operative deaths (4.9%); the operative risk increased with age and with the practice of valve replacement. Eleven of the 235 survivors (4.7%) were lost to follow-up. During the follow-up period (average 58 months) there were 37 late deaths of which nearly a half were due to left ventricular dysfunction. Multifactorial analysis identified cardiothoracic ratio and atrial fibrillation as predictive factors of late mortality whilst left ventricular ejection fraction and the type of surgery were related to the development of left ventricular dysfunction. The postoperative left ventricular ejection fraction was significantly lower after valve replacement than after valvuloplasty (11 +/- 13% vs 3 +/- 13%; p less than 0.01). These results are therefore in favour of early correction of severe mitral regurgitation by conservative surgery whenever possible. PMID- 2106305 TI - [Echocardiography in selecting patients to undergo Carpentier's mitral valvuloplasty]. AB - The aim of this study was to confront preoperative echocardiographic data with the anatomic operative findings in patients with mitral insufficiency (MI) undergoing Carpentier's mitral valvuloplasty in order to determine the mechanism(s) of the regurgitation, to classify MI by the echocardiographic changes and to thereby answer the question as to whether echocardiography can identify the patients likely to benefit from this operation. Between February 1985 and November 1987, 66 patients (47 men, 19 women, average age 58 +/- 9 years) with pure MI were referred for surgery with a view to mitral valvuloplasty. This operation was possible in 49 patients (2 of 6 rheumatic MI and 47 of 60 dystrophic MI). The sensitivity of echocardiography was excellent and its specificity very good in diagnosing prolapse of one or the other mitral leaflets. Echocardiography was not as good in distinguishing rupture from elongation of the chordae tendinae and myxoid degeneration from fibro-elastic leaflets. Echocardiography allowed preoperative classification of MI in 4 groups: Group 1 (n = 46) with prolapse of the posterior leaflet; Group 2 (n = 4) with prolapse of the anterior leaflet; Group 3 (n = 8) with prolapse of both mitral leaflets; Group 4 (n = 2) with abnormalities of the mitral annulus alone. Carpentier's valvuloplasty was possible in 43/46 patients in Group 1, 2/4 patients in Group 2, 1/8 patients in Group 3 and 1/2 patients in Group 4. In conclusion, echocardiography is a good tool for selecting patients with dystrophic MI for Carpentier's valvuloplasty. PMID- 2106306 TI - [Carotid sinus hypersensitivity. Medium and long-term development in patients treated by ventricular pacing]. AB - The problem of pacing patients with carotid sinus hypersensitivity (CSH) is the choice and criteria of selection of the pacing mode. The authors studied 29 patients with CSH treated by VVI pacing over a period of 10 years. The average follow-up was 34 months (range 6 to 96 months). Three of the 27 patients (11%) who were asymptomatic at the outset continued to have symptoms. The nature of the CSH was well-defined in 25 patients; 19 of the 20 cases of cardio-inhibitory CSH and 4 of the 5 cases of mixed CSH were asymptomatic. These two poor clinical results were analysed: the patient with the cardio-inhibitory CSH (one recurrence in 84 months) had a drop of 40 mmHg in systolic blood pressure which fulfilled criteria of the cardio-inhibitory form of CSH (a drop of 30 to 50 mmHg). The second case was a complete therapeutic failure with 3 recurrent syncopal episodes. The patient had a mixed form of CSH (B.P. drop of 65 mmHg) associated with a "pace maker syndrome" (drop of 50 mmHg in systolic blood pressure at the onset of VVI pacing without any sino carotid massage). The authors conclude that the cases of CSH which, during their investigation, are best corrected by dual chamber pacing or which are associated with a significant pacemaker effect or present retrograde ventriculo-atrial conduction, should receive dual-chamber pacemakers. PMID- 2106307 TI - [An attempt to quantify myocardial ischemia by selective coronary arteriography: determination of a new score. An initial study]. AB - An original model for estimating myocardial ischaemia from coronary arteriography is proposed. Four parameters are taken into consideration: anatomical variations, the myocardial mass perfused, the degree of reduction of basal flow across the stenosis, the eventual summation of several successive stenotic lesions. This scoring system was tested by simulation on a computer and evaluated in 100 anginal patients. Analysis of our preliminary results shows statistically significant differences in the score between the following groups of patients: patients with normal and those with abnormal LV wall motion; patients with and those without previous myocardial infarction; patients with Class II stable angina and those with other forms (III, IV and unstable angina). PMID- 2106308 TI - [Estimation of the long-term efficacy of anti-arrhythmia treatment with flecainide in ventricular tachycardia]. AB - Flecainide, a Class IC antiarrhythmic agent, was used in 12 patients with an average age of 57 years to treat spontaneous monomorphic sustained ventricular tachycardia (S-VT, n = 9), with a ventricular rhythm of 203 +/- 41 bpm (5 right bundle branch and 4 left bundle branch block pattern) and non-sustained ventricular tachycardia (NS-VT, n = 3). The patients had ischaemic heart disease (n = 5, including 2 cases of aneurysm), idiopathic dilated cardiomyopathy (n = 1), ventricular dysplasia (right, n = 1; left n = 2; biventricular, n = 1). The remaining 2 patients had no overt cardiac disease on coronary angiography. None of the patients had signs of cardiac failure; the left ventricular ejection fraction was 0.49 +/- 0.7. Before treatment, programmed ventricular stimulation (PVS) induced 12 S-VT (214 +/- 41 bpm) which reproduced the clinical VT in 8 out of 10 cases. A second series of electrophysiological studies was performed after an average of 5 weeks treatment with Flecainide 300 mg/day (200-400 mg). It was not possible to induce VT in 2 patients (17% total prevention); NS-VT replaced S VT in 4 patients (33%); S-VT was less rapid in 5 patients (at least 50 bpm slower) (41%); one patient had S-VT as rapid as before treatment (9%). The 12 patients were prescribed long-term Flecainide therapy. During follow-up there were 4 early (7, 10 and 15 days) and one late recurrence (16 months) (42% failure rate) whilst the other 7 patients had no further attacks of VT (follow-up of 19.1 +/- 5 months) (58% success rate).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106309 TI - [Aneurysm of the membranous ventricular septum. Apropos of 4 cases surgically treated]. AB - Four patients with aneurysms of the membranous ventricular septum were operated either because of complications or for associated malformations. The authors describe the anatomical, radiological and, above all, the echocardiographic and angiographic features of this malformation. Surgical management is necessary in complicated cases or when there are associated congenital malformations. The information provided by echocardiography in the diagnosis and follow-up of ventricular septal defects indicates that this malformation is not as rare as was previously thought. PMID- 2106310 TI - Tumor immunization. Improved results after vaccine modified with recombinant interferon gamma. AB - The purpose of this study was to determine if a 3-day in vitro culture of the murine neuroblastoma C1300 with 500 U/mL of recombinant interferon gamma resulted in a protective crossreactivity to parent C1300. Twenty A/J mice received either a vaccine of 1 x 10(6) irradiated C1300 tumor cells intradermally or an equivalent inoculum of C1300 that had been incubated in recombinant interferon gamma (C1300*). One week later, all animals were rechallenged with 1 x 10(6) viable C1300. Animals immunized with C1300* had a significantly delayed early tumor incidence that translated into a survival advantage for the group. At the time of tumor rechallenge, a significantly increased level of nonspecific systemic immunity was conferred by the C1300* immunization. Thus, modification of tumor with recombinant interferon gamma before introduction as a vaccine may improve that vaccine's protective capability. PMID- 2106311 TI - Costs, quality, and the volume of surgical oncology procedures. AB - We tested the hypothesis that hospital costs and outcome (ie, mortality) would differ for each surgeon by the volume of patients treated per diagnosis related group by individual surgical oncologists. All elective surgical oncologic admissions (N = 2627) to our hospital from 1985 to 1987 were divided into those patients treated by low-volume surgeons vs those patients treated by high-volume surgeons; 11.9% of patients not fitting these categories were excluded. Patients of the 57 low-volume surgeons utilized greater hospital resources (which resulted in losses instead of profits) and had a higher mortality compared with patients of the 17 high-volume surgeons. This was due, in part, to a greater severity of illness. These findings suggest that hospital costs and perhaps outcome may be related, at the individual surgeon level, to the volume of surgical procedures performed, and that the diagnosis related group prospective payment system may provide disincentives for low-volume surgeons. PMID- 2106313 TI - Increase in the catalytic rate of beta-galactosidase by selection in chemostats at changing dilution rates. AB - The experiments presented in this paper explore whether mutants with catalytically more active beta-galactosidase (E.C. 3.2.1.23) can be selected in lactose-limited chemostats. This experimental system has been chosen because lactose metabolism in Escherichia coli is well understood both from a biochemical and genetic point of view. In a lactose-limited chemostat with constant dilution rates, both beta-galactosidase and the lactose permease increased in quantity. The catalytic rate (kcat) of beta-galactosidase in populations showed no change. On the other hand, in chemostats with periodically changing dilution rates, the catalytic rate of beta-galactosidase increased dramatically. Therefore, the selection for beta-galactosidase with improved catalytic rate occurs in chemostats with fluctuating dilution rates but not in ones with constant dilution. These observations may be of value in the selection of other enzymes with enhanced catalytic rates. PMID- 2106312 TI - Diazepam-binding inhibitor: a neuropeptide and/or an acyl-CoA ester binding protein? PMID- 2106314 TI - Interaction of DnaK with ATP: binding, hydrolysis and Ca+2-stimulated autophosphorylation. AB - The autophosphorylation of DnaK from Escherichia coli using ATP as phosphate donor is markedly stimulated by Ca+2 and to a lesser degree by Mn+2. Mg+2 and other divalent ions are without effect in this reaction. Lanthanum, an agonist/antagonist of Ca+2, is also effective in stimulating the autophosphorylation. In contrast, Mg+2 but not Ca+2, markedly stimulates the hydrolysis of ATP catalyzed by DnaK. Also at 0 degrees, ATP forms a stable complex with DnaK without hydrolysis that is independent of cations. About 15% of the DnaK in E. coli is associated with membrane vesicles where it also can be phosphorylated in the presence of Ca+2. PMID- 2106315 TI - The effect of N-linked glycosylation on the substrate preferences of UDP glucuronosyltransferases. AB - The presence of potential N-linked glycosylation sites (Asn-X-Ser/Thr) in two forms of UDP glucuronosyltransferase, designated UDPGTr-2 and UDPGTr-4, has been deduced from cDNA sequence data. These forms were glycosylated when synthesized from expression vectors transfected into COS cells and were converted to faster migrating species on SDS polyacrylamide gels when treated with endoglycosidase H. The role of glycosylation was investigated by determining the substrate specificities and stabilities of the glycosylated enzymes and their unglycosylated variants which were synthesized in the presence of tunicamycin. Analysis of the activities towards 13 different aglycones showed that the glycosyl moiety was not essential for catalytic activity and had no effect on the substrate preference of each form. The stabilities of the proteins were not adversely affected by the absence of this posttranslational modification. A possible effect of N-linked oligosaccharides on the catalytic properties of these two forms of UDP glucuronosyltransferase is discussed. PMID- 2106316 TI - Dopachrome conversion factor functions as an isomerase. AB - Dopachrome conversion factor is an enzymatic activity associated with the pigmentary system which catalyzes the conversion of dopachrome, an intermediate in melanin biosynthesis, to dihydroxyindole-2-carboxylic acid (DHICA). To date, the mechanism of action of DCF has been unknown because all previous assays have employed a dopachrome substrate contaminated with L-dopa. It has therefore not been possible to determine whether L-dopa acts as a hydrogen donor in the reaction or whether the formation of DHICA occurs through an isomerization of dopachrome. In this study it is shown that DCF catalyzes the conversion of dopachrome to DHICA equally well in the presence or absence of L-dopa. The DCF mediated reaction thus appears to be an isomeric rearrangement of hydrogen ions from one portion of the dopachrome molecule to another. The results indicate that the name "dopachrome isomerase" appropriately describes the function of DCF. PMID- 2106317 TI - Multiple small molecular weight guanine nucleotide-binding proteins in human erythrocyte membranes. AB - Native membranes from human erythrocytes contain the following G proteins which are ADP-ribosylated by a number of bacterial toxins: Gi alpha and Go alpha (pertussis toxin), Gs alpha (cholera toxin), and three proteins of 27, 26 and 22 kDa (exoenzyme C3 from Clostridium botulinum). Three additional C3 substrates (18.5, 16.5 and 14.5 kDa) appeared in conditions of unrestrained proteolysis during hemolysis. SDS-PAGE separation of erythrocyte membrane proteins followed by electroblotting and incubation of nitrocellulose sheets with radiolabeled GTP revealed consistently four GTP-binding proteins with Mr values of 27, 26, 22 and 21 kDa. Although a 22 kDa protein was immunochemically identified as ras p21, the C3 substrate of 22 kDa is a different protein probably identifiable with a rho gene product. Accordingly, at least five distinct small molecular weight guanine nucleotide-binding proteins, whose functions are so far undetermined, are present in native human erythrocyte membranes. PMID- 2106318 TI - Determination of amyloid beta protein precursors harboring active form of proteinase inhibitor domains in cerebrospinal fluid of Alzheimer's disease patients by trypsin-antibody sandwich ELISA. AB - beta-Amyloid protein precursors (APP) having proteinase inhibitor domains (APPI) were quantified by a new sandwich enzyme linked immunosorbent assay for detection of active (free) form of proteinase inhibitors by using trypsin in place of the first antibody and by denaturation of APPI-trypsin complex in the microtiterplate. The concentration of APPs having APPI in cerebrospinal fluid of Alzheimer's disease patients was found, by this method, to be significantly elevated compared with those of multi-infarct dementia. PMID- 2106319 TI - Alanine: glyoxylate aminotransferase 1 is present in the peroxisomes of guinea pig kidney. AB - The subcellular distribution of alanine: glyoxylate aminotransferase 1 in guinea pig and rabbit kidneys was examined by centrifugation in a sucrose density gradient. The enzyme was located in the peroxisomes of guinea pig kidney and cross-reactive with the antibody against rat liver alanine: glyoxylate aminotransferase 1. This is the first report on the presence of the enzyme in the peroxisomes of mammalian kidney. The enzyme was found to be located in the mitochondria but not in the peroxisomes in rabbit kidney. PMID- 2106320 TI - Purification and properties of aldose reductase and aldehyde reductase from EHS tumor cells. AB - Engelbreth-Holm-Swarm (EHS) tumor cells were utilized as a model for investigating the production of basement membrane components. These cells contain two immunologically distinct NADPH-dependent reductases, aldose reductase (EC 1.1.1.21) and aldehyde reductase (EC 1.1.1.2), which were purified to apparent homogeneity by a combination of procedures which included ammonium sulfate fractionation, Sephadex G-75 gel filtration, Matrex Gel Orange A affinity chromatography, and chromatofocusing on Pharmacia Mono P. The molecular weights of aldose and aldehyde reductases were estimated to be 38K and 40K, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Substrate specificity studies showed that both enzymes were capable of reducing a variety of aldehydes to their respective alcohols; however, only aldehyde reductase oxidized L-gulonic acid. Surprisingly, both enzymes showed similar reactivities with D-glucose and D-galactose, suggesting that both aldose and aldehyde reductases may contribute to sorbitol production in the EHS tumor cell. The activities of both enzymes were increased by the presence of sulfate ion, but chloride ion decreased the activity of aldose reductase. Both aldose and aldehyde reductases were inhibited by a series of structurally diverse aldose reductase inhibitors. PMID- 2106321 TI - Aflatoxin B1-specific cytochrome P-450 isozyme (P-450-AFB) inducible by 3 methylcholanthrene in golden hamsters. AB - Hepatic microsomes of polychlorinated biphenyl (PCB)-treated Syrian Golden hamsters possessed a higher potency toward aflatoxin B1 activation, based on the Ames test, than other animal species. This activity was induced in hamsters preferentially by treatment with 3-methylcholanthrene rather than phenobarbital. The contribution of an isozyme of cytochrome P-450 (P-450-AFB) to the activity of hamster livers for aflatoxin B1 was studied. P-450-AFB, purified from 3 methylcholanthrene-treated hamster livers, was shown to possess the highest activation of aflatoxin B1 in the Ames test. The quantification of this isozyme by a fluorometric sandwich enzyme-linked immunosorbent assay (ELISA) demonstrated that P-450-AFB was induced mainly in Syrian Golden hamsters but not in Chinese hamsters, or in other species. This isozyme constitutes approximately 40% of the total cytochrome P-450 of the hepatic microsomes from 3-methylcholanthrene treated Golden hamsters but only 1% in the microsomes of phenobarbital-treated hamsters. Thus, we conclude that the high activity of Golden hamster livers towards aflatoxin B1 activation was due presumably to this distinct and unique cytochrome P-450 isozyme which was induced mainly by 3-methylcholanthrene in Golden hamsters. PMID- 2106322 TI - Distribution of cytochromes P-450, cytochrome b5, and NADPH-cytochrome P-450 reductase in an entire human liver. AB - In rat liver there appear to be significant differences between lobes in the concentration of individual cytochrome P-450 isozymes (Sumner and Lodola, Biochem Pharmacol 36: 391-393, 1987). Because studies in patients often rely on small pieces of liver obtained from diverse anatomical locations, it seemed important to determine if the cytochromes P-450 were also heterogeneously distributed in human liver. Accordingly, tissue was obtained from ten different locations in a single human liver including those most commonly biopsied by percutaneous needles, and by surgeons during laparotomy. The differences observed between locations in the microsomal concentrations of carbon monoxide-binding protein (total cytochrome P-450), cytochrome b5, and NADPH-cytochrome P-450 reductase appeared to be small and were not statistically significant. Likewise, no significant differences were observed between locations in the specific content of HLp, HLp3, HLj, HLx or P450MP. However, the specific concentrations of HLd varied almost 2-fold between the microsomes and this was statistically significant in some cases (P less than 0.05). Our results suggest that, in human livers, regional differences in the content of cytochromes P-450 are generally small but may be significant for some isozymes. With the exception of HLd, tissue obtained by percutaneous or surgical liver biopsies is probably representative of the entire organ with regard to the enzymes assayed. PMID- 2106323 TI - Zinc increases EGF-stimulated DNA synthesis in primary mouse hepatocytes. Studies in tumor promoter-treated cell cultures. AB - To investigate factors influencing cell proliferation, cells are often cultured in serum-free medium. In the present study it is shown that addition of zinc chloride (40 microM) to primary mouse hepatocytes, cultured in Dulbecco's minimal essential medium, markedly enhanced growth factor (EGF)-stimulated [3H]thymidine incorporation into DNA. Treatment of cell cultures with phenobarbital or 3,4,3',4'-tetrachlorobiphenyl (enzyme inducers and tumor promoters in vivo) or with 12-O-tetradecanoylphorbol-13-acetate (the classical skin tumor promoter) further increased EGF-stimulated DNA synthesis. The results emphasize the need to adequately substitute zinc in serum-free cultured cells. PMID- 2106324 TI - A lectin-like receptor on murine macrophage is involved in the recognition and phagocytosis of human red cells oxidized by phenylhydrazine. AB - Phenylhydrazine (Phz) is a powerful hemolytic agent which has several effects on both normal and G6PD deficient red blood cells (RBCs). We have studied the mechanism of removal of Phz-damaged human RBCs by murine macrophages. Phagocytosis of Phz-treated RBCs was found to be 50 RBCs/100 mac as compared to 2 RBCs/100 mac of the controls. EGTA and sodium azide inhibited the phagocytosis, indicating a requirement for both calcium ions and energy. Incubation of macrophages with sugars such as D-galactose or D-mannose reduced phagocytosis of Phz-treated RBCs by up to 60%, indicating the involvement of a macrophage lectin like receptor in the recognition of Phz-treated RBCs. The presence of serum in the phagocytosis assay did not affect either phagocytosis of Phz-treated RBCs or inhibition by sugars. beta-Galactosidase, but not neuraminidase, treatment of RBCs caused a significant inhibition in phagocytosis of Phz-treated RBCs. These results suggest that galactosyl residues are exposed on RBC membrane during oxidation, probably not as a result of desialization. We conclude that Phz treated RBCs are detected as damaged cells mainly due to sugar changes on their membrane, which are directly recognized by lectin-like receptors on the macrophages. PMID- 2106325 TI - Metalloproteinases and cartilage proteoglycan depletion in chronic arthritis. Comparison of antigen-induced and polycation-induced arthritis. AB - Chronic monarticular arthritis can be induced in ovalbumin-sensitized rabbits by intraarticular injection of ovalbumin (antigen-induced arthritis) or in naive rabbits by injecting hyaluronic acid mixed with the polycation poly-D-lysine (polycation-induced arthritis). Both models show some points of similarity, including joint swelling, the presence of inflammatory leukocytes and the inflammatory mediator prostaglandin E2, and the kinetics of cartilage proteoglycan loss. However, the assessment of the capacity of synovial lining and articular cartilage to synthesize and secrete neutral metalloproteinases reveals a difference between these models. We found that articular cartilage from the inflamed joints of rabbits with antigen-induced arthritis did not synthesize neutral metalloproteinases, although the synovial lining did. In contrast, both the synovial lining and the articular cartilage from the inflamed joints of rabbits with polycation-induced arthritis synthesized neutral metalloproteinases. These findings suggest that in inflammatory synovitis, different mechanisms can operate to produce damage to the matrix of articular cartilage. PMID- 2106326 TI - Interleukin-1 release by rat synovial cells is dependent on sequential treatment with gamma-interferon and lipopolysaccharide. AB - To determine the potential regulatory mechanisms involved in synovial cell interleukin-1 (IL-1) release, the ability of gamma-interferon (gamma-IFN) to influence IL-1 release was assessed. Rat synovial cells cultured in the presence of a variety of stimuli, including lipopolysaccharide (LPS), failed to release IL 1. However, pretreatment of synovial cells with gamma-IFN, followed by LPS stimulation, resulted in increased levels of intracellular IL-1 as well as release of IL-1 from the cell. The level of IL-1 release was dependent on the concentration of both gamma-IFN and LPS, and on length of exposure to the gamma IFN. The kinetic and dose requirements for gamma-IFN-dependent IL-1 release were similar to those for Ia antigen expression, but LPS was necessary for IL-1 messenger RNA induction, intracellular IL-1 accumulation, and IL-1 release. In addition, sequential treatment, i.e., gamma-IFN followed by LPS, was essential for IL-1 induction. Substitution of phorbol ester or calcium ionophore for gamma IFN did not result in similar IL-1 release. In addition, induction of IL-1 messenger RNA by another stimulus was not sufficient to result in IL-1 release following LPS treatment. These results suggest that release of IL-1 by rat synovial cells requires the production of a regulatory signal, which is inducible by gamma-IFN. PMID- 2106327 TI - Prolonged improvement of Raynaud's phenomenon and scleroderma after recombinant tissue plasminogen activator therapy. AB - We describe a patient with systemic sclerosis (SSc; scleroderma) characterized by severe Raynaud's phenomenon, cutaneous sclerosis, and digital ulceration and subsequent amputation who was treated with recombinant tissue plasminogen activator (rt-PA) after acute myocardial infarction. She showed prompt improvement of the Raynaud's phenomenon and healing of the digital ulceration. After 18 months of followup, the Raynaud's phenomenon has remained mild, and there has been improvement in the cutaneous sclerosis. Since the pathophysiology of SSc has been associated with disorders of fibrinolysis and coagulation, this patient represents an interesting index case that might prompt further evaluation of rt-PA therapy in carefully selected patients. PMID- 2106328 TI - Promoting value in health care: the new Agency for Health Care Policy and Research. PMID- 2106329 TI - Acquired factor VIII inhibitor with squamous cell cancer of the epiglottis. AB - A 73-year-old woman developed an acquired factor VIII inhibitor in association with squamous cell carcinoma of the epiglottis. The inhibitor was an IgG antibody that reacted with factor VIII in vitro and in vivo. Intravenous gamma-globulin therapy was successful in reducing the inhibitor so that curative surgery could be undertaken. With surgical resection of the tumor the inhibitor did not recur. The relevance of this type of coagulation disorder to the surgical management of the patient's head and neck cancer is discussed. PMID- 2106330 TI - Expression of beta amyloid protein precursor mRNAs: recognition of a novel alternatively spliced form and quantitation in Alzheimer's disease using PCR. AB - We have analyzed alternatively spliced beta amyloid protein precursor (beta APP) mRNAs by using the polymerase chain reaction to amplify beta APP cDNAs produced by reverse transcription. With this approach the three previously characterized beta APP mRNAs (beta APP695, beta APP751, and beta APP770) are readily detected and compared in RNA samples extracted from specimens as small as a single cryostat section. We show that the results obtained with this method are not affected by partial RNA degradation and use it to identify a novel alternatively spliced beta APP714 mRNA that is present at low abundance in each of the many human brain regions, peripheral tissues, and cell lines that we have examined; demonstrate that nonneuronal cells in the adult human brain and meninges produce appreciable beta APP695, beta APP751, and beta APP770 mRNA; and identify changes in beta APP gene expression in the AD brain and meninges that may contribute to amyloid deposition. PMID- 2106331 TI - Mutational and gene dosage analysis of calcium-activated potassium channels in Drosophila: correlation of micro- and macroscopic currents. AB - In Drosophila, two Ca2(+)-activated K+ currents, ICF and ICS, have previously been distinguished in conventional voltage clamp experiments. The slowpoke (slo) mutation eliminates ICF specifically. We report that in patch clamp recordings a single-channel Ca2(+)-activated K+ current is readily distinguished from other channel activities in normal larval muscle membrane, whereas no such current is observed in slo muscles. This single-channel current thus correlates with the macroscopic ICF. No obvious differences in amplitude or properties were detected between normal (+/+) and heterozygous (slo/+) ICF channels in whole-cell voltage clamp recordings or single-channel patch clamp recordings. These results are consistent with the hypothesis that slo is a structural gene for the ICF channels only under certain conditions. The selective effect of the slo mutation may reflect a defect in a regulatory mechanism that is specific for the functioning of the ICF channel protein. PMID- 2106333 TI - Characterization of the human peripheral lung adenosine receptor. AB - Because adenosine narrows asthmatic airways, is released during hypoxia and by mast cells, and is antagonized by theophylline, it may play a role in asthma. I characterized the first step in pulmonary responses to adenosine: its adenosine receptor. Plasma membranes, prepared from macroscopically normal human peripheral lung, were incubated with 10 nM 5'-N-ethylcarboxamido[3H]adenosine ([3H]NECA) and various concentrations of competing ligand under experimentally determined optimal conditions: 4 degrees C, pH 7.4, 5 mM MgCl2, 1.8 mg protein/ml, 30-min incubation time. Bound and free ligand were separated by rapid vacuum filtration, and the radioactive counts were analyzed using a weighted, non-linear, least squares curve-fitting program, LIGAND. Analyzed together, the data from the lungs of 6 patients revealed a single binding site with a dissociation constant (Kd) for NECA of 200 nM +/- 14% and a receptor concentration of 543 fmol/mg protein +/ 13%. Analyzed separately, the individual Kds ranged from 133 to 430 nM and the receptor concentrations from 338 to 811 fmol/mg protein. Adenosine receptor ligands competed with NECA in an A2 rank order of potency: NECA greater than 8 phenyltheophylline greater than 3-isobutyl-1-methylxanthine greater than theophylline greater than N6-L-phenylisopropyladenosine greater than N6-D phenylisopropyladenosine greater than N6-cyclohexyladenosine. Theophylline bound to the receptor with an inhibition constant (Ki = 70.9 microM +/- 28%) near the therapeutic range (28 to 56 microM). Cromolyn also bound with high affinity (Ki = 5.42 microM +/- 47%). I conclude that human lung adenosine receptors: (1) are single-site receptors, probably of the A2 subtype and (2) bind to both theophylline and cromolyn. PMID- 2106332 TI - Interferon-gamma and synthesis of surfactant components by cultured human fetal lung. AB - We examined the effects of interferon-gamma (IFN-gamma) on development of the surfactant system in alveolar epithelial cells of fetal lung. Explants of second trimester human fetal lung were cultured for 1 to 6 days in serum-free medium containing recombinant human IFN-gamma (0.03 to 30 ng/ml) and/or dexamethasone (10 or 100 nM). Treatment for 3 days with IFN-gamma alone, dexamethasone alone, and IFN plus dexamethasone increased the content of surfactant protein A (SP-A, 28 to 36 kD) by approximately 3-, 2.5-, and 10-fold, respectively. The biphasic response pattern of SP-A to dexamethasone (stimulation initially and inhibition with continued culture) was not altered by the presence of IFN-gamma. IFN-gamma also stimulated accumulation of SP-A mRNA (2.7-fold at 24 h) but did not affect the levels of mRNAs for surfactant protein B (18 kD) and surfactant protein C (5 kD). To assess the effect of IFN-gamma on synthesis of surfactant lipids, we determined the content of phosphatidylcholine, the rate of labeled choline incorporation into phosphatidylcholine, saturation of newly synthesized phosphatidylcholine, and the activity of fatty acid synthetase, a glucocorticoid inducible enzyme. Treatment of explants for 5 days with IFN-gamma had no effect on these parameters. Studies by light and electron microscopy revealed little difference between control and IFN-treated explants with regard to cell viability and epithelial cell differentiation. We conclude that IFN-gamma has a selective stimulatory effect on SP-A among surfactant components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106334 TI - A comparative study of prostacyclin infusion given before and during cardiopulmonary bypass to assess the first pass effect of the circuit on platelet number and function. AB - Platelet damage during cardiopulmonary bypass (CPB), although proportional to the duration of bypass, may result in significant dysfunction after the initial contact with an extracorporeal circuit, the so-called 'first pass' phenomenon. The platelet sparing effect of prostacyclin (PGI2) infusion was studied in a double-blind randomized trial on male patients undergoing coronary artery bypass grafts to assess the effect of the 'first pass' through the CPB circuit. Prostacyclin infusion was begun before the onset of CPB or during CPB in two groups which were compared to a placebo control group. A standardized anaesthetic, surgical and perfusion technique were used. Preoperatively and during surgery at pre-set intervals, whole blood platelet aggregation was studied using ADP and collagen agonists. Platelet numbers and function measured by ADP aggregation were conserved in the two PGI2 groups. There was no significant difference between the treated groups. We conclude, therefore, that the initial contact of platelets with the CPB circuit, in the absence of PGI2 did not irreversibly affect platelet function. In addition, the hypotensive action of PGI2 was easier to control once on bypass. It may therefore be preferable to delay PGI2 infusion until CPB has been established. PMID- 2106335 TI - Respiratory and sedative effects of clobazam and clonazepam in volunteers. AB - 1. The respiratory and psychomotor effects of two benzodiazepines used mainly as anticonvulsants were compared in healthy volunteers, using a double-blind placebo controlled design. 2. Clobazam (10 and 20 mg) produced significantly fewer psychomotor side effects than clonazepam (0.5 and 1 mg). Neither drug at either dose affected the ventilatory response to CO2. 3. Although clonazepam produced significant effects on psychomotor performance, these did not correlate with plasma drug concentration. 4. Our studies provide further evidence that at the doses chosen clobazam is considerably less sedating than clonazepam. Further investigation is required into the tolerance profile of both drugs in patients. PMID- 2106336 TI - The effect of indomethacin on the kinetics of histamine, 48/80 and antigen wealing. AB - 1. The kinetics of weal formation and disappearance following intradermal injection of histamine, compound 48/80 and antigen were measured in indomethacin and inert geltreated human forearm skin. 2. Rates of formation went in descending order for histamine, 48/80 and antigen; rate constants of disappearance for equal sized weals were the same for histamine and 48/80 but were much less for antigen. The corresponding half-lives were 77, 73 and 160 min for histamine, 48/80 and antigen weal disappearance respectively. 3. Cyclo-oxygenase inhibition by topical indomethacin had no effect either on the immediate weal and flare responses or on the rates of formation and disappearance of the weals. 4. These findings together with previous studies using H1-receptor antagonists indicate that 48/80 acts by histamine release but that antigen releases both histamine and an additional material or materials which are not related to cyclo-oxygenase activity. 5. Exacerbation of chronic idiopathic urticaria by cyclo-oxygenase inhibitors is therefore likely to be part of the urticarial disease process. PMID- 2106337 TI - Disposition of pravastatin sodium, a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects. AB - Pravastatin sodium, a competitive inhibitor of HMG-CoA reductase, is a new orally effective hypocholesterolaemic agent. In a two-way crossover study, eight healthy male subjects each received an intravenous and an oral dose of [14C]-pravastatin sodium. The oral absorption of [14C] activity from pravastatin sodium was about 34% and the oral bioavailability was about 18%, suggesting first-pass metabolism of pravastatin. After the intravenous dose, the recovery of radioactivity averaged 60% and 34% in urine and faeces, respectively. Corresponding values were 20% (urine) and 71% (faeces) for the oral dose. The estimated average plasma elimination half-life of pravastatin was 0.8 and 1.8 h for the intravenous and oral routes, respectively. The average values for total and renal clearances were 13.5 and 6.3 ml min-1 kg-1, respectively, and the steady-state volume of distribution averaged 0.51 kg-1. These results suggest that both kidney and liver are important sites of elimination for pravastatin. PMID- 2106338 TI - Obstetric and paediatric collaboration to reduce morbidity after preterm birth. PMID- 2106339 TI - Bacillus-induced endophthalmitis: new series of 10 cases and review of the literature. AB - We reviewed the charts of 10 patients who were admitted to the Massachusetts Eye and Ear Infirmary over a 10-year period with the diagnosis of Bacillus species endophthalmitis. To our knowledge this is the largest single series in the literature and includes the first two reported cases of Bacillus endophthalmitis following glaucoma filtering procedures. Seven cases developed following penetrating ocular trauma. One occurred in an intravenous drug abuser. Five eyes ultimately underwent enucleation; only the two eyes that developed endophthalmitis after elective surgery retained useful vision. Review of the literature indicates that parenteral and intravitreal antibiotic prophylaxis against endophthalmitis after penetrating ocular trauma should include gentamicin, in combination with vancomycin or clindamycin, to provide adequate coverage against infection with Bacillus spp., as prognosis is poor once infection is established. Bacillus spp. cultured from ocular tissues or fluids should not be dismissed as contaminants. PMID- 2106340 TI - Postenucleation orbital radiotherapy for the treatment of malignant melanoma of the choroid with extrascleral extension. AB - The outcome is reported in 17 patients in whom an eye was enucleated for malignant melanoma of the choroid with extrascleral extension and who subsequently underwent adjuvant external beam radiotherapy to the orbit as the primary treatment of the extraocular spread of their tumour. Extrascleral extension was encapsulated in five, non-encapsulated in two, and had been surgically transected at enucleation in 10 cases. All the patients have been followed up from enucleation to the present day. Orbital recurrence occurred in only one patient. The overall actuarial survival rate was 51% at 5 years, 44% at 10, and 33% at 15 years. A low orbital recurrence rate of 6% compares very favourably with published figures for this event after enucleation for melanoma with extrascleral extension but without radiotherapy. Adjuvant orbital radiotherapy may have a place in the treatment of selected cases of extracleral extension of intraocular malignant melanoma. PMID- 2106341 TI - Effect of donor parameters on primary graft failure and the recovery of acuity after keratoplasty. AB - A retrospective evaluation was made of 983 penetrating corneal grafts. Donor corneas stored in either K-Sol or McCarey-Kaufman media had a significantly greater rate of primary graft failure (about 2%) than those kept in moist chamber storage (0%). Selected subgroups of 50 corneas from each storage system were studied to determine the time taken to reach a postoperative acuity of 6/12. No significant correlation was found between this time and either the duration of storage of donor corneas or the age of donor. A significant delay in recovery of visual acuity was found with increasing age of recipient. The increased average time from donor death to surgery for K-Sol (56 hours) and McCarey-Kaufman (40 hours) corneas compared with moist chamber corneas (15 hours) facilitated the scheduling of surgery at the cost of increased chance of primary graft failure. PMID- 2106342 TI - High concentration of free trimethyllysine in red blood cells. AB - A high concentration of a basic unidentified amino compound was found in the blood of rats. It was isolated and identified as N epsilon,N epsilon,N epsilon trimethyllysine by paper chromatography, thin-layer chromatography, high performance liquid chromatography and amino acid analyzer. It was localized exclusively in red blood cells in the blood of rats. Free trimethyllysine was also determined in the liver, kidney, spleen, brain, muscle, heart and testis of rat. The concentration of free trimethyllysine in red blood cells was more than 10-times as high as that in the other tissues. This compound in red blood cells was found in different species of animals. The relationship between this free trimethyllysine and carnitine was discussed. PMID- 2106343 TI - Squid proteoglycans: isolation and characterization of three populations from cranial cartilage. AB - Squid cranial cartilage is poor in proteoglycans. They were extracted by 2% SDS and purified by isopycnic centrifugation in the presence of detergent. According to their buoyant density and hydrodynamic size they were fractionated into three structurally different populations of Mr 1.3.10(6), 0.6.10(6) and 1.0.10(6). The proteoglycans of each population differ in the number of oversulphated chondroitin sulphate chains, ranging from two to five, in the number and size of uronic acid and sulphate containing oligosaccharides and in the size of their core protein. The majority, if not all, of the oligosaccharides are linked to the protein via an O-glycosidic bond involving galactosamine and most likely xylose. The chondroitin sulphate chains are segregated on a small peptide segment of the molecule which also contains a large proportion of the oligosaccharides. The proteoglycans have no tendency to interact with hyaluronate. PMID- 2106344 TI - Isolation and characterization of an intracellular aminopeptidase from the extreme thermophilic archaebacterium Sulfolobus solfataricus. AB - An intracellular aminopeptidase (EC 3.4.11.-) was purified from the extreme thermophilic archaebacterium, Sulfolobus solfataricus. The molecular weight of the native enzyme was about 320,000, as calculated by gel-filtration studies, and a subunit Mr of 80,000 was estimated by SDS-polyacrylamide gel electrophoresis. The temperature optimum of the enzyme was at 75 degrees C and the pH optimum was found to be 6.5. The aminopeptidase was highly active against the chromogenic substrates L-Leu-p-NA and L-Ala-p-NA. The enzyme was inhibited by EDTA, but the activity could be partially restored by removal of the EDTA and incubation with Co2+ or Mn2+. Bestatin, a typical inhibitor of aminopeptidase, fully inhibited the enzyme activity, but inhibitors of serine proteinases had no effect. Beside a high thermostability, the enzyme showed a remarkable stability against 6 M urea, organic solvents and acetonitrile. PMID- 2106345 TI - Unusual fucoidin-binding properties of chymotrypsinogen and trypsinogen. AB - Previous work (Jones, R. (1987) Cell Biol. Int. Reports 11, 833 and Jones et al. (1988) Development 102, 781-792) has shown that sperm proacrosin (the zymogen form of the acrosomal proteinase acrosin, EC 3.4.21.10) has the capacity to recognize and bind sulphated polysaccharides and that this property is important for the initial stages of fertilization in mammals. To investigate whether this behaviour is specific to proacrosin, a variety of other proteinases (chymotrypsinogen, trypsinogen, thrombin, elastase, plasminogen, pepsin, Streptomyces griseus proteinase and V8 proteinase from Staphylococcus aureus) were immobilized on nitrocellulose and probed with [125I]fucoidin. Only chymotrypsinogen and trypsinogen retained significant amounts of the probe with Kd values of 1.4.10(-6) M and 3.0.10(-5) M, respectively. Proteinase inhibitors were ineffective as blocking agents suggesting that enzymic activity is not involved in recognition. However, the tertiary structure of the proteins is important, since cleavage of intramolecular disulphide bonds with 2 mercaptoethanol reduced binding by 50-60%. Competition experiments with a variety of mono- and polysaccharides suggest that the number and disposition of sulphate groups is critical for interaction with basic residues on the protein. It is concluded that, like proacrosin, chymotrypsinogen and trypsinogen are bifunctional proteins. PMID- 2106346 TI - Sex- and age-related variations in the in vitro heparin-releasable lipoprotein lipase from mononuclear leukocytes in blood. AB - An in vitro heparin release of lipoprotein lipase (LPL) from whole blood, mainly from monocytes, was demonstrated by (1) the time-course of lipolytic activity with the presence of 10 U/ml heparin at 37 degrees C, (2) the distribution of LPL activity in monocyte and lymphocyte fractions, (3) an immuno-inactivation with anti-LPL immunoglobulin (IgG) and (4) responses to various compounds such as NaCl, protamine sulfate, heparin, and serum activator. The in vitro heparin releasable LPL activity from blood correlated well with the LPL activity of postheparin plasma obtained from both normolipidemic and hyperlipidemic rabbits. Studies in humans revealed sex- and age-related variations in the in vitro heparin-releasable LPL from monocytes in the blood of 134 normal subjects and 24 hypertriglyceridemic subjects: The mean LPL activity was significantly higher in normal females over the age of 30, than in the corresponding males. In the hypertriglyceridemic group, the LPL activity was also higher in females than in males, but it was not significant. The in vitro heparin-releasable LPL activity from monocytes in blood was comparable to the LPL activity derived from adipose tissue and postheparin plasma, and thus it reflects lipoprotein metabolism. PMID- 2106347 TI - Comparative effects of simvastatin (MK-733) and pravastatin (CS-514) on hypercholesterolemia induced by cholesterol feeding in rabbits. AB - The preventive effects of simvastatin (MK-733) and pravastatin (CS-514), 3 hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors, on hypercholesterolemia induced by 0.25% cholesterol feeding were compared in rabbits. MK-733 (6, 2 and 0.7 mg/kg) was found to prevent the increase in serum total cholesterol levels dose-dependently. High dose CS-514 (18 mg/kg) also limited the increase in the cholesterol levels, but medium (6 mg/kg) and low doses (2 mg/kg) of CS-514 were ineffective in preventing it. MK-733 inhibited the increase in VLDL and LDL cholesterol levels dose-dependently. MK-733 suppressed the increase in serum phospholipid levels. MK-733 inhibited the accumulation of cholesterol in the liver. The high dose of CS-514 also limited it. High dose MK 733 (6 mg/kg) reduced the cholesterol concentration in gallbladder bile. Neither MK-733 nor CS-514 affected bile acid excretion in the gallbladder bile. High dose MK-733 decreased the lithogenic index. MK-733 increased the number of LDL receptors, and high dose CS-514 also increased it. The suppressive effect of CS 514 on serum cholesterol levels at 18 mg/kg was found to be less than that of MK 733 at 0.7 mg/kg. PMID- 2106348 TI - Altered arachidonic acid metabolism during differentiation of the human monoblastoid cell line U937. AB - The human cell line U937 was used as a model for differentiation along the mononuclear phagocyte lineage. Following treatment with the phorbol ester TPA, PGE2 and TxB2 secretion was induced 50-100-fold, and both PGF2 alpha and PGI2 levels became detectable in the supernatant of TPA-differentiated U937 cells. The content of the prostaglandin precursor, arachidonic acid, remained unchanged in the cellular phospholipids of undifferentiated and TPA-differentiated U937 cells. Of the enzymes involved in the availability and metabolism of arachidonic acid, phospholipase A2 activity was increased 2-fold in the membranes of TPA differentiated U937 cells, whereas lysophosphatide acyltransferase activity remained unaltered. Cyclooxygenase activity, however, was enhanced 5-10-fold, which was due to enhanced expression of the enzyme as demonstrated by dot-blot analysis. The data suggest that the capacity to secrete prostaglandins is acquired during differentiation with TPA and results mainly from an increased cyclooxygenase activity. Despite the capacity of TPA-differentiated U937 cells to synthesize prostaglandins, none of the known monocytic stimuli further stimulated prostaglandin secretion in TPA-differentiated U937 cells. Generation of leukotrienes appears to represent a later state in the differentiation along the monocyte-macrophage lineage, since neither LTB4 nor cysteinyl-leukotrienes were detectable in the supernatants of either undifferentiated or TPA-differentiated U937 cells. PMID- 2106349 TI - Inhibition of phosphatidylinositol-specific phospholipase C by phosphonate substrate analogues. AB - Non-hydrolysable analogues of phosphatidylinositol were synthesized and tested as inhibitors of phosphatidylinositol-specific phospholipase C from Bacillus cereus. In these molecules, the phosphodiester bond of phosphatidylinositol hydrolyzed by the phospholipase was replaced by a phosphonate linkage and a simpler hydrophobic group replaced the diacylglycerol moiety. One of the phosphonates also contained a carboxylate functional group suitable for matrix attachment. All three synthetic phosphonates inhibited the phospholipase C activity in a concentration dependent manner, with the analogue most closely resembling the structure of the natural substrate, phosphatidylinositol, being the most potent inhibitor. The data indicate that phosphonate analogues of phosphatidylinositol may be useful for study of phospholipase C and other proteins interacting with myo-inositol phospholipids. PMID- 2106350 TI - Deviation from homeoviscous adaptation in Escherichia coli membranes. AB - The process by which an organism changes the composition of its membranal fatty acids in response to growth temperature, so as to maintain optimal membrane functioning, is known as homeoviscous adaptation (HA). One expression of HA is the constancy of the fluorescence polarization (P) of the lipophilic probe 1,6 diphenyl-1,3,5-hexatriene (DPH) in membranes of cells grown at various temperatures. The P of DPH in the membranes of Escherichia coli was shown by us to be inversely proportional to bacterial growth rate on different carbon sources. This result, implying failure of HA, is now complemented by measurements of DPH lifetimes, which indicate that the dominant variables contributing to the drop in P are (a) the order parameter of the membrane, which goes down, and (b) the fluidity, which may slightly increase. These are then the changes induced by enhanced growth rate. Two additional effects, cell membrane permeability and sensitivity to thermal shock, determined by the diffusion of o nitrophenylgalactoside (ONPG) and by exposure to 52 degrees C, respectively, are reported to increase with growth rate. We can now conclude that there is a deviation from the principle of HA in E. coli grown at various rates, brought about by controlling the growth media at constant temperatures. PMID- 2106351 TI - Retroviral-mediated transfer and amplification of a functional human factor VIII gene. AB - Hemophilia A results from a deficiency in factor VII (FVIII), a cofactor in the intrinsic pathway of blood coagulation. As an approach toward genetic therapy of this disease, we constructed a retroviral vector encoding human FVIII and a selectable and amplifiable genetic marker, human adenosine deaminase (Ada). A retrovirus packaging line was transfected with this vector and stable transformants were selected for Ada expression. Isolated transformants produced both FVIII activity in the conditioned medium and retrovirus capable of transferring the Ada selectable marker and FVIII expression to the mouse 3T3 fibroblasts. Selection of virus-producer cell lines for increasing levels of Ada expression yielded a 20-fold increase in both FVIII expression and viral titer. Similarly, selection of infected 3T3 fibroblasts for Ada gene amplification yielded a 20-fold increase in FVIII expression. The results demonstrate the feasibility of retrovirus-mediated transfer of human FVIII, and also the utility of selection for gene amplification to increase retrovirus titers in producer cell lines as well as expression levels in infected cells. PMID- 2106352 TI - Clinical implications of increased plasma levels of CD8 in patients with hairy cell leukemia. AB - Plasma levels of soluble T-suppressor/cytotoxic antigen (sCD8) were measured at diagnosis or before systemic treatment in 69 patients with hairy cell leukemia (HCL). The 49 nonsplenectomized patients were characterized by high concentrations of sCD8 antigen as compared with 17 controls (P less than .0001). The median sCD8 level in non-splenectomized patients was 1,050 U/mL (range: 160 to 2,400 U/mL) and was significantly higher (P less than .0001) than the median of 275 U/mL (range: 20 to 1,080 U/mL) in splenectomized patients. The relationship of sCD8 to clinical response to subsequent interferon alpha (IFN alpha) treatment was analyzed. Patients who showed subsequent hematologic response with normalization of all blood counts had significantly lower levels of sCD8 concentrations at diagnosis than those who did not (P = .0056). Furthermore, normalization of sCD8 during IFN alpha treatment paralleled the achievement of normal counts in peripheral blood, whereas soluble interleukin-2 receptor (sIL 2R) levels remained high in most patients after 12 to 15 months of treatment. We speculate that activation of suppressor/cytotoxic T cells might play a role in myelosuppression, and its modulation during treatment with IFN alpha correlates with normalization in peripheral blood counts. PMID- 2106353 TI - An improved clonal excess assay using flow cytometry and B-cell gating. AB - In humans with B-cell malignancies, the presence of monoclonal B lymphocytes (clonal proliferation) can be detected by comparing the fluorescence intensity distributions of lymphocytes stained with anti-kappa and anti-lambda reagents. The sensitivity of previously described single-color immunofluorescence techniques to low levels of clonal excess is limited by background from cytophilic immunoglobulins on non-B cells and by the low proportion of circulating B cells in individuals with minimal disease. We have used two-color immunofluorescence and B-cell gating to develop an improved assay that avoids false positives due to non-B cells, without requiring restrictive light scatter gates that may exclude true positives. This method is sensitive to 0.2% monoclonal B cells admixed with fresh normal lymphocytes, to 0.6% monoclonal B cells admixed with normal lymphocytes that have been stored for up to 72 hours, and readily detects 1% monoclonal cells in patient specimens. The two color B cell gated assay offers sensitivity equivalent to the single-color assay and improved specificity for detection of low levels of clonal excess. PMID- 2106354 TI - Synergistic effects of oxidation and deformation on erythrocyte monovalent cation leak. AB - The normal red blood cell (RBC) membrane is remarkable for its durability (eg, preservation of permeability barrier function) despite its need to remain deformable for the benefit of microvascular blood flow. Yet, it may be hypothesized that the membrane's tolerance of deformation might be compromised under certain pathologic conditions. We studied this by subjecting normal RBC in viscous suspending medium (20% dextran) to elliptical deformation induced by application of shear stress under physiologic conditions (290 mOsm/L, 37 degrees C, pH 7.40) in the presence of ouabain and furosemide. Measurement of resulting net passive K efflux ("K leak") demonstrated that shear-induced RBC deformation causes K leak in a dose-dependent fashion at shear stresses far below the hemolytic threshold, an effect shown to be due to deformation per se. To model the specific hypothesis that oxidatively perturbed RBC membranes would be abnormally susceptible to this potentially adverse effect of deformation, we treated normal RBC with the lipid peroxidant t-butylhydroperoxide. Under conditions inducing only minimal K leak due to either oxidation alone or deformation alone, deformation of peroxidant-pretreated RBC showed a markedly enhanced K leak (P less than .001). This highly synergistic oxidation-plus deformation leak pathway is less active at low pH, is neither chloride-dependent nor calcium-dependent, and allows K efflux to be balanced by Na influx so there is no change in total monovalent cation content or cell density. Moreover, it is fully reversible since deformation-induced K leak terminates on cessation of shear stress (even for oxidant-treated RBC). Control experiments showed that our results are not explained simply by hemolysis, RBC vesiculation, or development of prelytic pores. We conclude that oxidation and deformation individually promote passive leak of monovalent cation through RBC membranes and that a markedly synergistic effect is exerted when the two stresses are combined. We hypothesize that these findings may help explain the abnormal monovalent cation leak stimulated by deoxygenation of sickle RBC. PMID- 2106355 TI - Enhancement of tumor-initiating activity of DMBA by the carbamate fungicide mancozeb. PMID- 2106356 TI - Structure-toxicity relationships for nonpolar narcotics: a comparison of data from the tetrahymena, photobacterium and pimephales systems. PMID- 2106357 TI - The response of circulating parameters of bone mineral metabolism to ethanol- and EDTA-induced hypocalcemia in the rat. AB - The mechanism of the acute hypocalcemia that follows acute ethanol administration has not been established. Measurements of parathyroid hormone (PTH) performed during this hypocalcemia reveal conflicting results. We compared the response of ionized calcium (Ca2+), immunoreactive PTH and bone Gla protein (BGP) after ethanol- and EDTA-induced hypocalcemia. 103 male Sprague Dawley rats each weighing approximately 300 g received ethanol and 100 rats of similar weight received EDTA. In each of these studies the animals were divided into experimental and control groups. The ethanol-treated rats received ethanol, 2 g/kg body weight, by ip injection and the EDTA-treated rats received 100 mg EDTA/kg body weight by im injection. Controls received normal saline by the corresponding route of administration. Rats were sacrificed at 0, 30, 60, 90, 180 and 360 min for the measurement of the above parameters. In both experimental groups Ca2+ levels were significantly reduced to the same degree by 30 min with return to control values by 360 min. There was no significant difference in immunoreactive PTH, and BGP between control and ethanol-treated groups. In the EDTA-treated rats, however, PTH values were significantly increased at 30 (P less than 0.005) and BGP at 60 and 90 minutes (P less than 0.005) vs. control. Therefore acute ethanol administration appears to blunt the PTH response to hypocalcemia. A direct inhibitory effect of ethanol on osteoblast function ie BGP production cannot be excluded. In addition, PTH may stimulate BGP. PMID- 2106358 TI - Urinary excretion of pyridinium crosslinks: a new marker of bone resorption in metabolic bone disease. AB - The pyridinium derivatives hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are intermolecular crosslinking compounds of collagen which are only present in its mature form. Contrasting to the wide distribution of type I and II collagens, HP and LP are absent from skin, ligament and fascia, and their major sources are bone and cartilage. Using a specific HPLC assay, we have determined the 24-h excretion of HP and LP crosslinks in normal adults of both sexes, in patients with primary hyperparathyroidism and in patients with Paget's disease of bone before and after intravenous treatment with amino-propylidene bisphosphonate (APB). Mean adult normal values were 33 +/- 13 pmol/mumol creatinine for HP and 6.3 +/- 3.4 pmol/mumol creatinine for LP. In women, menopause induced a 2-3-fold increase of HP and LP reflecting the well documented postmenopausal increase of bone turnover. In the urine of patients with primary hyperparathyroidism and of patients with active Paget's disease of bone, urinary crosslinks were significantly higher than in age-matched controls, with a mean 3- and 12-fold increase, respectively. Urinary excretion of hydroxyproline is a well recognized but poorly sensitive marker of bone turnover, reflecting resorption. In the same patients, the effect of menopause and disease state on hydroxyproline excretion was much less dramatic than on HP and LP. During intravenous APB treatment of pagetic patients, there was an early decrease of HP and LP, which was significant after 24 h and reached 62% at 4 days, contrasting with a late and milder decrease of urinary hydroxyproline. Because APB is a potent inhibitor of resorption which does not have a direct short-term effect on bone formation, these data also indicate that urinary excretion of HP and LP reflect only collagen degradation occurring during osteoclastic resorption and not the degradation of newly synthesized collagen. We conclude that urinary HP and LP excretion represents the first sensitive and specific marker of bone resorption. Its use should be valuable in the clinical investigation of metabolic bone diseases, especially osteoporosis. PMID- 2106360 TI - CO2 waveforms revisited. PMID- 2106361 TI - A method for the assessment of the output of irregularly shaped electron fields. AB - A simple approach to the calculation of dose in cone-collimated electron fields is presented. The method accounts for variations in lateral scatter with field size using a Clarkson Integration. The reduction in output by an irregularly shaped aperture is evaluated based on measurements of the output at various distances from the aperture in a field 2.5 cm in diameter. The first 14 months of clinical use were analysed and it is shown that in 42 out of 600 calculations, the cutout factor was less than 0.95 and that in 77% of these, the calculation method was accurate to +/- 3%. PMID- 2106359 TI - The effects of gamma-interferon on human peripheral blood monocyte/macrophage mediated bone particle degradation. AB - gamma-Interferon (IFN-gamma) has recently been demonstrated to inhibit the ability of mononuclear phagocytes to degrade bone particles. We have further addressed the specificity, potency and mechanism of this activity using human recombinant IFN-gamma. Adherent peripheral blood mononuclear leukocytes from normal human volunteers were cultured with washed, sieved (less than or equal to 75 microns) 45Ca-labelled rat bone particles for 3 days, after which bone particle degradation (7.1 +/- 1.6%, n = 11) was calculated from the fraction of 45Ca released into the medium. As little as 5 U/ml IFN-gamma significantly suppressed bone particle degradation and 50 U/ml was associated with consistent marked suppression (74.0 +/- 3.5% inhibition, P less than 0.001, n = 11). IFN gamma was not suppressive if added to cells 24 h or more after exposure to bone particles. Addition of indomethacin (10 microM) did not reverse the effect of IFN gamma, suggesting that it was not prostaglandin-mediated. In addition, 1,25(OH)2D3 (10 nM) did not remove the inhibitory effect of IFN-gamma. Contact of mononuclear phagocytes with bone particles and secretion of soluble factors from these cells have both been demonstrated to play a role in their ability to degrade bone particles. IFN-gamma (50 U/ml) inhibited monocyte/macrophage interaction with another unopsonized surface, i.e., one micron fluorescent latex particles, decreasing the number of internalized particles from 12.6 +/- 2.9 per cell to 5.9 +/- 1.4 per cell (P less than 0.01, n = 15), as measured using flow cytometry. However, binding of bone particles by the cells was not diminished by IFN-gamma. Exogenous alpha-interferon and human recombinant IL-1 beta, TNF-alpha, and lymphotoxin did not alter bone particle degradation. In addition, endogenous IL-1 beta release from human monocyte/macrophages exposed to bone particles was negligible and unaffected by IFN-gamma. We conclude that IFN-gamma is a potent and specific inhibitor of monocyte/macrophage-mediated bone particle degradation, and that this activity does not appear to be due to effects on the ability of monocytes to bind bone particles or to release IL-1 in response to the particles. PMID- 2106362 TI - The effects of L-dopa on in vitro dopamine release from striatum. AB - We have examined the effects of L-dihydroxyphenylalanine (L-DOPA) on endogenous dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) efflux from superfused striatal slices prepared from adult male rats. Superfusion with L-DOPA (10 microM) caused a modest elevation in the tissue levels of DA and greatly increased the basal efflux and stimulation-evoked overflow of DA. Stimulation of slices under Ca2(+)-free conditions abolished DA overflow occurring in the absence of L-DOPA, but reduced DA overflow in the presence of L-DOPA by only 56%. Ca2(+)-independent DA release was not reduced by nomifensine. Destruction of DA terminals by pretreatment with 6-hydroxydopamine did not alter the capacity of L DOPA to elevate tissue DA content. However, it attenuated the impact of L-DOPA on DA efflux, although this effect was somewhat smaller than was the apparent loss of DA terminals. These results suggest the following conclusions: (1) L-DOPA increases both the spontaneous and depolarization-induced release of DA; (2) some of the DA formed from L-DOPA can be released in response to depolarization by a process that does not involve either Ca2(+)-dependent exocytosis or reverse transport; and (3) most but not all of the DA efflux occurring in the presence of L-DOPA represents DA released from DA terminals. Furthermore, the observations suggest that the loss of DA terminals due to the progression of Parkinson's disease may be importantly involved in the gradual loss of clinical efficacy of the drug during chronic treatment. PMID- 2106363 TI - Characterization of synaptophysin and G proteins in synaptic vesicles and plasma membrane of Aplysia californica. AB - Two components of synaptic terminals that may be involved in transmitter release are synaptophysin (p38) and G proteins. In order to study release mechanisms in Aplysia californica we have prepared subcellular fractions from nervous tissue to characterize and localize these components. We identify Aplysia synaptophysin by Western blot analysis with monoclonal antibody SY38, find that it is enriched in synaptic vesicles, and, using immunocytochemistry, show that it is localized to neuropil. These characteristics indicate that Aplysia synaptophysin is closely related to mammalian synaptophysin; it appears to be much smaller, however, having a mass of 28 kDa instead of 38 kDa. We previously determined that G protein subunits in Aplysia are enriched in neuropil and synaptosomes. We now show that within the synaptic terminal the pertussis toxin-sensitive alpha subunit as well as the beta-subunit are associated with plasma membrane using [32P]ADP-ribosylation and Western blotting with G protein-specific antibodies. PMID- 2106364 TI - An endogenous inhibitor of N-acetylgalactosaminyltransferase inhibits retina neuron differentiation in culture. AB - An inhibitor of N-acetylgalactosamine:GM3, N-acetylgalactosaminyltransferase (EC 2.4.1.92) from chicken blood serum, was tested for its activity on embryonic chicken neural retina in culture. The inhibitor did not change the cellular protein content of the cultures but produced a significant reduction of the labeling of gangliosides. The ratio of labeling of GD3 to GD1a increased from about 0.1 to about 0.8 in the cells cultured without or with the inhibitor, respectively. A striking effect of the inhibitor was seen on the morphology of the neurons, those cultured in its presence being practically devoid of neurites. Glial flat cells were apparently not affected. PMID- 2106366 TI - Identification of H1 visual interneuron in Drosophila by [3H]2-deoxyglucose uptake during stationary flight. AB - High-resolution 2-deoxyglucose (2-DG) neuronal activity labeling is used to identify a visual interneuron in Drosophila by its stimulus-specific uptake of [3H]2-DG during stationary flight in a well-characterized behavioral situation. With a single rotating stripe as visual stimulus a neuron is heavily labeled that has not been described in Drosophila before but is homologous to the extensively studied H1 visual interneuron of larger diptera. Labeling of this cell is inconspicuous in Drosophila if the animal is stimulated with a rotating striped drum. PMID- 2106365 TI - Torpedo synaptophysin: evolution of a synaptic vesicle protein. AB - Synaptophysin is an integral membrane protein of synaptic vesicles found in neurons and endocrine cells. Synaptophysin monomers associate into hexamers forming a large conductance channel. We present an analysis of synaptophysin from the nervous system of the marine ray Torpedo californica. Analysis of cDNA clones reveals a 62% amino acid similarity between the Torpedo and rat sequences. The 4 hydrophobic membrane spanning domains and the glycosylation site are conserved. In contrast, the two intravesicular loops connecting the membrane spanning regions, show varying degrees of sequence conservation, suggesting that portions of these domains may play critical functional roles. The carboxyterminal tail has been proposed to bind calcium and is a major site for tyrosine phosphorylation. The precise sequence of this region has almost completely diverged while the proline-tyrosine rich nature is maintained. Blotting studies reveal the RNA and the protein in nervous system tissues and demonstrate that the molecule copurifies with cholinergic synaptic vesicles. PMID- 2106367 TI - Expression of neurofilament proteins in granule cells of the cerebellum. AB - We have used a panel of monoclonal antibodies directed against the low, middle and high molecular weight subunits of neurofilament triplet, to study their expression in mouse cerebellar granule cells. We demonstrate that in situ such cells only express the 2 lower molecular weight subunits either at various developmental stages or in the adult. The same results were obtained in vitro. This pattern of neurofilament protein expression in adult granule cells is therefore similar to that observed in developing neurons but differs from most neurons in the adult brain. The retention of such 'immature' pattern of neurofilament protein expression throughout adulthood could explain the lack of cytologically identifiable intermediate filaments in these neurons when examined with conventional electron microscopic techniques. It furthermore suggests that various neuronal populations might be characterized by the expression of specific subsets of neuronal intermediate filaments. PMID- 2106368 TI - Livingston-Wheeler therapy. AB - Livingston-Wheeler's cancer treatment is based on the belief that cancer is caused by a bacterium she has named Progenitor cryptocides. Careful research using modern techniques, however, has shown that there is no such organism and that Livingston-Wheeler has apparently mistaken several different types of bacteria, both rare and common, for a unique microbe. In spite of diligent research to isolate a cancer-causing microorganism, none has been found. Similarly, Livingston-Wheeler's autologous vaccine cannot be considered an effective treatment for cancer. While many oncologists have expressed the hope that someday a vaccine will be developed against cancer, the cause(s) of cancer must be determined before research can be directed toward developing a vaccine. The rationale for other facets of the Livingston-Wheeler cancer therapy is similarly faulty. No evidence supports her contention that cancer results from a defective immune system, that a whole-foods diet restores immune system deficiencies, that abscisic acid slows tumor growth, or that cancer is transmitted to humans by chickens. PMID- 2106369 TI - Evaluation of periodic breast cancer screening with mammography: methodology and early observations. 1966. PMID- 2106370 TI - The Hippocratic Oath. PMID- 2106371 TI - Improving cancer treatment by expanding clinical trials. PMID- 2106372 TI - 1989 survey of physicians' attitudes and practices in early cancer detection. PMID- 2106373 TI - The relationship between spinal trabecular bone mineral content and iliac crest trabecular bone volume. AB - The relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume has been studied in 84 patients, 23 with primary osteoporosis, 19 with osteoporosis secondary to inflammatory bowel disease, and 42 with nonsteroid-treated rheumatoid arthritis. Spinal trabecular bone mineral density was measured in the first three lumbar vertebrae by quantitative computed tomography, and iliac crest trabecular bone volume was assessed histomorphometrically in sections from trans-iliac biopsies using computerized techniques. In all 84 patients, there was a significant positive correlation between the two measurements (r = 0.60, P less than 0.001). However, when the three patient groups were analyzed separately, a significant correlation was found in the group with secondary osteoporosis (r = 0.65, P less than 0.01) but not in the patients with primary osteoporosis (r = 0.07) or rheumatoid arthritis (r = 0.19). These results indicate that the relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume differs according to the underlying disease process, these differences possibly reflecting variations in skeletal patterns of bone loss in different types of osteoporosis. PMID- 2106374 TI - Current bone mass and body weight changes in alcoholic males. AB - The relationships between current bone mass and changes in body weight were studied in 45 male veterans whose weights and heights at the time of enlistment into the Armed Forces over 40 years ago were obtained, and who were, or had been, chronic alcohol abusers. Those who lost and those who gained weight did not appear to differ in severity of alcoholism but differed in femoral neck cortical thickness, iliac crest trabecular bone volume, and lumbar bone mineral density, the former being significantly lower. Subjects with a hip fracture and those with spinal fractures are significantly lighter now, but were initially of similar weight to those without fractures. We conclude that maintenance of body weight protects against bone loss and fracture even in the presence of chronic alcoholism. PMID- 2106375 TI - Alcohol decreases serum osteocalcin in a dose-dependent way in normal subjects. AB - The acute effect of 25 and 50 g of alcohol on the variation in serum osteocalcin, a specific and sensitive marker of bone formation, and on serum cortisol and serum parathyroid hormone (PTH)(1-84) was calculated in 6 normal young adults. They were studied during three periods, each lasting from 4 p.m.-7:30 a.m. Alcohol was ingested between 4:15 and 5 p.m. during period two and three. Blood was taken at 4 p.m. and every 15 minutes from 4:30 til 6 p.m., followed by hourly sampling until 12 p.m. The last blood sample was taken after an overnight fast at 7:30 a.m. Initial and end values before and after alcohol ingestion did not differ significantly from control values. Repeated measures analysis of variance showed that 50 g of ethanol decreased serum osteocalcin significantly (P less than 0.02) and increased serum cortisol (P less than 0.05) during the 4-12 p.m. interval. The interaction of 50 g of ethanol on the variation in serum osteocalcin was already significant during the first 2 hours (P less than 0.02), where no significant effect on serum cortisol could be detected. Although insignificant, the same pattern was observed after 25 g of alcohol. There was no significant change in the variation of serum iPTH(1-84) during the 4-6 p.m. after alcohol intake. We conclude that 3-4 drinks of alcohol taken over 45 minutes decreases serum osteocalcin in a dose-dependent way. The time lag between changes in serum osteocalcin and cortisol indicates that the decrease in serum osteocalcin is not related to the increase in serum cortisol. PMID- 2106376 TI - Sex- and age-related changes in bone and serum osteocalcin. AB - We measured bone osteocalcin concentrations in EDTA extracts from iliac crest cortical bone specimens obtained postmortem from 63 men and 71 women (age range 19-90 years), and serum osteocalcin levels in healthy blood donors, 49 men and 49 women (age range 21-65 years). Bone and serum osteocalcin concentrations were higher in men than in women, and an age-related decline was observed in both sexes. In women, however, a temporary increase in serum (P less than 0.05) osteocalcin was seen in the sixth decade. This study shows sex- and age-related changes in bone osteocalcin consistent with changes in serum osteocalcin, confirming that serum measurement of osteocalcin reflects bone levels. As osteocalcin reflects osteoblastic activity and thus bone formation, the overall decline in bone and serum osteocalcin in men and women, and the increase in serum osteocalcin in the sixth decade in women, indicate that aging is associated with a decrease in bone formation and turnover and that osteoblastic activity and bone turnover are stimulated at the menopause. PMID- 2106377 TI - Effect of heparin on bone formation in cultured fetal rat calvaria. AB - To assess the effects of heparin on bone formation we measured [3H]proline incorporation into collagenase-digestible (CDP) and noncollagen protein (NCP), [3H]thymidine (TdR) incorporation into DNA, and DNA content in 21-day-old fetal rat calvaria cultured in BGJ medium with bovine serum albumin for 24-96 hours. Heparin at 5-125 micrograms/ml decreased TdR incorporation by 26-51% at 24 and 96 hours. At 96 hours, heparin 5, 25, and 125 micrograms/ml decreased [3H]proline incorporation into CDP by 41, 48, and 32%, respectively, with no significant change in NCP. To evaluate the possible role of PGE2 in these inhibitory responses, media PGE2 concentration was measured and the effects of heparin on CDP labeling and DNA synthesis were tested in the presence of indomethacin, piroxicam, and flurbiprofen to inhibit endogenous prostaglandin E2 (PGE2) production and in the presence of a high concentration (10(-7) M) of exogenous PGE2. Heparin did not alter PGE2 production at 24 hours but at 48 hours there was a significant reduction. At 96 hours, indomethacin (10(-6) M) inhibited [3H] proline incorporation into CDP by 38% but had no effect on the labeling of NCP. Heparin had no further significant inhibitory effect in the presence of indomethacin. Piroxicam and flurbiprofen did not alter DNA content and had a smaller inhibitory effect than indomethacin on the labeling of CDP. Moreover, addition of heparin produced a further inhibition of CDP and DNA content and finally, heparin decreased CDP labeling by 71% in the presence of PGE2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106378 TI - Bone marrow fat content in relation to bone remodeling and serum chemistry in intact and ovariectomized dogs. AB - It was previously shown that 11 months after ovariectomy the volume fraction of trabecular bone in the spine and 11th rib medullary canal of Beagle dogs (6 control, 9 ovariectomized) was significantly reduced. In this paper it is shown that these changes are accompanied by increased marrow fat volume in the 11th rib (59.0 +/- 9.5% vs. 44.3 +/- 10.0%). Conversely, the volume fraction of functional (hematopoietic) cells in the marrow was reduced by ovariectomy. Additionally, variations in marrow fat volume were tested for correlation with 22 other variables pertinent to bone physiology. Marrow fat volume was significantly positively correlated with serum osteocalcin, rib trabecular bone porosity, rib cross-sectional area, and gains in body weight. It was negatively correlated with serum estrogen concentrations and the extent of rib trabecular surfaces labeled with tetracycline. PMID- 2106379 TI - Hyperostosis induced by the bisphosphonate (2-PEBP) in the oophorectomized rat. AB - To prevent the high turnover bone remodeling associated with acute estrogen deficiency, the bisphosphonate [2-(2-pyridinyl) ethylidene-BP] (2-PEBP) was administered to oophorectomized (OX) rats. Three groups of 15 rats each (250 g) were studied. Group (Gp) A was sham operated, Gp B was OX, and Gp C received 2 PEBP (1.72 mg/kg/day) intraperitoneally for 3 days commencing 4 days postoophorectomy. Oophorectomy was confirmed with serum estradiol measurements. Blood samples were collected on days -7, 0, 7, 14, 21, and 28 for ionized calcium (Ca2+), PTH, and serum bone gla protein (BGP). Rats received tetracycline for bone histomorphometric labeling. All results were compared to Gp A. Body weight increased significantly in Gps B and C (P less than 0.005 by day 28). There was no significant difference in Ca2+, and PTH levels in Gps B and C were similar to Gp A. BGP levels were significantly higher on day 28 in Gp B (P less than 0.05). In Gp C, BGP levels were significantly decreased on days 7, 21, and 28 (P less than 0.03). Gp B revealed increased bone turnover without loss of bone volume (BV/TV). BV/TV was significantly increased in Gp C despite a decrease in parameters of bone formation and normal osteoclast number. In conclusion, 2-PEBP in the OX rat inhibited bone resorption more than formation with resultant hyperostosis. Serum BGP appeared to be a good marker of the changes observed on bone histomorphometry. PMID- 2106380 TI - Distribution of fluoride concentration in the rat's bone. AB - The present study was undertaken to determine the fluoride distribution profile in the rat femur. Male Wistar rats were divided into four groups and given water containing 0, 25, 50, and 100 ppm of fluoride, respectively, for 10 weeks. The fluoride distribution from the periosteum to the endosteum was determined in each specimen after sampling using the abrasive microsampling technique. In the outer circumferential lamellae, the concentration of fluoride was relatively high in the periosteal layer and then decreased gradually towards its interior. In the haversian and interstitial lamellae, it was lower and roughly constant through the tissue. In the inner circumferential lamellae, it rose again to reach the highest level towards the endosteal surface. Fluoride concentration throughout the cortex increased significantly with increasing intake of fluoride. These increases were especially marked at periosteal and endosteal surfaces. PMID- 2106381 TI - Properties of phosphorylated 32 kd nonamelogenin proteins isolated from porcine secretory enamel. AB - Enamel proteins were isolated from specific locations of permanent porcine incisors at various developmental stages, namely, the outer (young) and inner (old) secretory, and maturing (chalk-like in appearance) enamel. The selective adsorption of these matrix proteins onto hydroxyapatite (HA) crystals was investigated in the presence of dissociative agents. The results showed that the proteins with the highest adsorption affinity were present at the highest concentration in the vicinity of the ameloblasts, i.e., in the outer enamel layer; a substantial reduction of these proteins was observed in the older (inner) secretory enamel and in the tissue in the maturing stage. An interesting finding was that a group of proteins having molecular masses of 32 kd present only in the inner secretory enamel, adsorbed strongly onto the HA crystals and were potent inhibitors of HA crystal growth. This 32 kd group contains phosphorylated glycoproteins; they are rich in Pro, Glu, Gly, and Asp and the N terminal sequence was LXQVPGRIPPGYGRPPTP-, having no resemblance to the reported sequences of amelogenins. It was also found that the 32 kd moieties remained only as trace constituents in the maturing enamel, suggesting that most of them were removed as soluble constituents in the tissue fluid or further degraded by enzymatic activity during the late secretory stage. The results obtained support the view that amelogenetic mineralization is regulated by the presence of various organic matter and, importantly, that their efficacy as inhibitors of mineralization may be modulated through their degradation. PMID- 2106382 TI - Blood gas and hematological changes in experimental peracute porcine pleuropneumonia. AB - The effect of experimental, peracute, porcine pleuropneumonia on arterial blood gases, acid base status, the leukogram, and gross and microscopic lung structure was studied in nine growing pigs (mean weight +/- SD 10.6 +/- 2.0 kg). Pigs were inoculated intranasally with a virulent serotype 5 isolate of Actinobacillus pleuropneumoniae, and all showed signs typical of the disease within four hours. Death occurred in all pigs from 4.5 to 32 hours postinoculation (mean 14 hours). Gross and microscopic changes were typical of porcine pleuropneumonia in all pigs. Changes in the leukogram included a rapid decline in total white cells, segmented neutrophils, lymphocytes, monocytes, and eosinophils. Pigs maintained alveolar ventilation throughout the study as arterial CO2 tension was unchanged; however, arterial O2 tension and pH decreased from (mean +/- SD) 95.2 +/- 5.7 torr and 7.463 +/- 0.018 at baseline to 62.1 +/- 12.3 torr and 7.388 +/- 0.045, respectively, within 90 minutes prior to death. The data showed that in this model of peracute porcine pleuropneumonia, progressive ventilatory failure was not a feature of the disease, and the blood gas values and acid base status were maintained within physiological ranges. The histopathological hematological and physiological findings were consistent with the hypothesis that peracute porcine pleuropneumonia resembles septic shock. PMID- 2106383 TI - Chemosensitivity correlation between the primary tumors and simultaneous metastatic lymph nodes of patients evaluated by DNA synthesis inhibition assay. AB - The chemosensitivities of primary tumors (PT) and simultaneous metastatic lymph nodes (MN) to mitomycin C (MMC), 5-fluorouracil (5-FU), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), carboquone (CQ), or cisplatin (CDDP) were assessed in a group of 29 patients (11 gastric, 8 colorectal, 4 breast, and 6 other cancers) by a DNA synthesis (3H-thymidine incorporation) inhibition assay. PT and MN from the same patient showed heterogeneity in chemosensitivity. MN were more sensitive to the agents than PT. PT were sensitive to 5-FU, whereas MN were sensitive to CDDP. An analysis of the sensitivity correlations showed that the sensitivities of PT to MMC, 5-FU, CQ, and CDDP correlated with each other, but ADR sensitivity correlated with only CQ sensitivity. The sensitivities of MN correlated with each other, except for those to ADR and CDDP. In contrast, MMC, ADR, or CQ sensitivity showed a correlation between PT and MN. These results suggest that patients should be treated according to the sensitivity of the target lesion. However, if the sensitivity assay is not available, the sensitivity correlation may be useful when choosing the agent. It also may be important that ADR sensitivity does not correlate with the sensitivities of other agents. PMID- 2106384 TI - The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence. AB - Testicular function was evaluated in 75 boys after treatment for Hodgkin's disease with involved-field or extended-field irradiation and stage-dependent chemotherapy (vincristine, prednisone, procarbazine, Adriamycin [doxorubicin], and cyclophosphamide [OPPA/COPP]). Although pubertal development and testosterone levels were normal in all patients, 18 of 75 (24.0%) had elevated basal and 65/74 (87.8%) elevated stimulated luteinizing hormone (LH) levels, demonstrating chemotherapy-induced Leydig cell damage. In addition, there was a 40.5% and 53.4% incidence of elevated basal and stimulated FSH values, respectively, indicating severe impairment of spermatogenesis as confirmed by azoospermia in four patients. Testicular dysfunction was observed in patients treated before as well as during puberty. The incidence of elevated basal follicle stimulating hormone (FSH) and LH values was significantly higher in patients who had received higher cumulative doses of chemotherapy, i.e., 28.9% and 13.2% with two OPPA, 45.5% and 36.4% with two OPPA/two COPP, and 62.5% and 43.8% with two OPPA/four to six COPP, respectively. Chemotherapy for Hodgkin's disease causes a high and apparently dose-related incidence of testicular dysfunction in prepubertal as well as in pubertal boys affecting Leydig cell function as well as spermatogenesis. Circumstantial evidence indicates that procarbazine is the major gonadotoxic agent involved. PMID- 2106385 TI - Small testicles with impaired production of sperm in adult male survivors of childhood malignancies. AB - Testicular size has been studied in 66 adult men who survived leukemia (n = 14) or cancer (n = 52) in childhood. Mean follow-up time was 14.5 years. The testicular size was measured as the length and breadth in mm; testicular volume index was calculated. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and prolactin were measured. A sperm sample was obtained from 46 men. The patients had smaller testicles than healthy medical students; 51 had small testicles. The size was the smallest in patients who survived leukemia. Multivariate analysis showed that the variables with independent effects on testicular size were cranial and testicular irradiation and therapy with cyclophosphamide. Sperm production was dependent on testicular size. We conclude that determination of serum FSH combined with testicular size may offer a practical approach for predicting the subsequent testicular damage in boys with malignancies. PMID- 2106386 TI - Actinic cheilitis. Treatment with the carbon dioxide laser. AB - Actinic cheilitis is a premalignant condition that can be treated in several ways. A total of 43 patients with biopsy-proven actinic cheilitis were treated with the carbon dioxide (CO2) laser. After follow-up of at least 10 months, 26 patients thought that the lip was cosmetically improved, and 40 thought that the function of the lip was improved or had not changed. Complications were few and included only mild hypertrophic scarring, which resulted most often from the diagnostic biopsy and was corrected with topical or intralesional steroids or no therapy except simple massage. The CO2 laser is a simple, inexpensive, effective therapy for actinic cheilitis. PMID- 2106387 TI - Susceptibility to lysis of pulmonary alveolar macrophages by human lymphokine activated killer cells. AB - In this study we addressed the question of whether lymphokine-activated killer (LAK) cells, besides killing neoplastic cells, may exert a certain degree of lysis on the normal counterpart; in particular we took into consideration the toxicity against pulmonary alveolar macrophages (PAM). We demonstrated that human LAK cells generated in vitro following incubation of peripheral blood mononuclear cells with recombinant interleukin 2 for 4 days were able to lyse normal PAM in a 4-h 51Cr release assay. Similarly, PAM recovered from patients suffering from nonneoplastic interstitial lung disorders, i.e., sarcoidosis and hypersensitivity pneumonitis, were shown to be susceptible to the cytotoxic function provided by LAK cells. Both autologous and allogeneic PAM were lysed by LAK cells, thus suggesting that the phenomenon we observed does not require a major histocompatibility complex restriction. Preincubation of PAM under study with gamma-interferon did not affect their susceptibility to the lysis mediated by LAK cells. Furthermore, cold target inhibition assay demonstrated that normal PAM could efficiently compete with both NK-sensitive and NK-resistant target lines for the binding sites on LAK cells, thus indicating that the putative receptor(s), or at least the mechanism of target recognition, is shared by PAM and these different target cell lines. The evidence herein provided that LAK cells are cytotoxic to normal, nontransformed PAM points out that the pathogenetic mechanisms involving this self-addressed lytic activity could account for some adverse reactions related to LAK/interleukin 2 immunotherapy. PMID- 2106388 TI - Protein kinase C-induced stimulation or inhibition of cellular proliferation in a murine macrophage tumor cell line. AB - M5076, a tumorigenic murine macrophage cell line, demonstrates diverse proliferative responses to a panel of protein kinase C activators. Thus, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate and mezerein potently inhibit cellular proliferation (by greater than 90%), whereas the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol markedly stimulates proliferation of serum-starved, quiescent M5076 cells. Another DG analogue, 1,2 dioctanoyl-sn-glycerol, has no effect on growth. However, all of these agents induce expression of c-fos oncogene mRNA levels to a similar magnitude and activate protein kinase C as determined by Mr 80,000 phosphorylation. Levels of c fos protein induced by these treatments were markedly different with the antiproliferative agents producing greater c-fos protein levels. PMID- 2106389 TI - Growth inhibition of human melanoma tumor xenografts in athymic nude mice by swainsonine. AB - Swainsonine, an inhibitor of alpha-mannosidases, has been shown to block experimental metastasis of B16F10 melanoma and MDAY-D2 lymphoid tumor cells in syngeneic mice. In this report we demonstrate that swainsonine also reduces the growth rate of human melanoma cells in vitro and in vivo. Graded doses of swainsonine were administered either orally or via implanted Alzet miniosmotic pumps to athymic nude mice bearing subcutaneously implanted human MeWo melanoma cells. Swainsonine at 10 micrograms/ml in the drinking water or 0.5 mg/kg/day administered by miniosmotic pump reduced the growth rate of the MeWo tumors by approximately 50% and inhibited the expression of complex-type oligosaccharides in tumors and host intestine by only 10-20%. Swainsonine doses of 4 mg/kg/day reduced expression of complex-type oligosaccharides by 85% in vivo but afforded no additional inhibitory effect. A glycosylation mutant of MeWo called 3S5 has a defect in the synthesis of complex-type asparagine-linked oligosaccharides resulting in incomplete processing similar to that observed in swainsonine treated MeWo tumor cells. Swainsonine did not inhibit the proliferation of 3S5 cells in vitro nor the growth of 3S5 tumors in nude mice. The results suggest that expression of highly branched complex-type oligosaccharides commonly associated with the malignant phenotype may provide the tumor cells with a growth advantage. PMID- 2106390 TI - Glucocorticoid effects on myeloma cells in culture: correlation of growth inhibition with induction of glucocorticoid receptor messenger RNA. AB - Glucocorticoids are widely used for the treatment of multiple myeloma. To investigate the direct actions of glucocorticoids on myeloma cells, we have used three cell lines of human multiple myeloma, OPM-1, OPM-2, and RPMI 8226. When growth curves of these cells were examined, OPM-1 cells were resistant, while OPM 2 were sensitive to dexamethasone (DEX). In cultures of OPM-2 cells, addition of DEX led to virtual cessation of growth, with only 16% of the residual cells viable after 4 days. RPMI 8226 appeared to be slightly sensitive, showing some slowing of growth for several days in DEX, with later recovery. Viabilities of OPM-1 and RPMI 8226 cells were not affected. Secretion of immunoglobulin (Ig lambda) was also partially suppressed, by 30% in OPM-2 and 14% in OPM-1. No significant suppression was observed in RPMI 8226. To explore the mechanism of these differential responses to the steroid, glucocorticoid receptor (GR) was examined. Binding assays showed high affinity binding sites in all three cell lines: 64 +/- 11 fmol/10(6) cells in OPM-1, 78 +/- 14 in OPM-2, and 62 +/- 16 in RPMI 8226. Nuclear transfer of GR and DNA-cellulose binding after heat activation appeared similar in all three cell lines. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cytosol proteins labeled with [3H]dexamethasone mesylate showed a GR of Mr 95,000 in all three. When GR mRNA was studied in these cells, all of them had GR mRNA of approximately 7 kilobases, but OPM-2 and RPMI 8226 had 3 times more GR mRNA than OPM-1. OPM-2 GR mRNA was induced 2-fold by DEX treatment at 5 x 10(-9) M or greater. OPM-1 GR mRNA was much less sensitive, with no response at less than 10(-6) M DEX and only 1.5-fold induction at that concentration. These results demonstrate that some myeloma cells can be killed by a direct action of glucocorticoids. The quantity and affinity of GR in the cells were not predictive of this response. Therefore, we propose that the resistance of OPM-1 and the relative resistance of RPMI 8226 to glucocorticoid inhibition of cell growth is by post-receptor mechanisms. The high sensitivity of induction of GR mRNA in OPM-2 may correlate with glucocorticoid-evoked cell kill. PMID- 2106391 TI - L-deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson's disease. AB - Six patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) on levodopa treatment participated in an open-label trial of L-deprenyl (Eldepryl) in conjunction with Sinemet. Deprenyl (10 mg/day) allowed a slight but not statistically significant 22% reduction of total daily levodopa intake after 4 weeks of treatment, with a significant but unsustained reduction in the number of daily "off" periods and an increase in the portion of waking day spent "on." Pharmacokinetic studies revealed no effect of deprenyl on the plasma levodopa concentration vs. time curve, or the coefficient of variation (C.V.) of plasma levodopa levels measured over an 8-h period. Plasma DOPAC levels were unaffected, suggesting that the majority of peripheral DOPAC is generated by action of MAO-A. For most patients, benefit was not maintained. Two patients have continued taking the drug, and both have enjoyed significant reductions in total levodopa dose. Both have mild end-of-dose failure and little dyskinesia. Since no changes in peripheral pharmacokinetics of levodopa could be demonstrated, any therapeutic action of deprenyl in PD would appear to be due to prolongation of dopaminergic activity within the CNS. PMID- 2106392 TI - Lysing of fresh human tumor by a cytotoxic factor derived from autologous large granular lymphocytes independently of other known cytokines. AB - During interaction with autologous tumor cells large granular lymphocytes (LGL) of cancer patients released a soluble cytotoxic factor, termed LGL-derived cytotoxic factor, which mediated lysing of autologous fresh tumor cells. The cytotoxic factor was compared with purified human recombinant cytotoxic cytokines, including tumor necrosis factor (TNF), lymphotoxin (LT), interferon (IFN) alpha, IFN gamma, interleukin-1 alpha (IL-1 alpha) and IL-2. The LGL cytotoxic factor exhibited cytotoxicity against autologous and allogeneic fresh human tumor cells in an 18-h 51Cr-release assay, while these target cells were resistant to lysing by any of the recombinant cytokines. Mixtures of recombinant(r) TNF, rLT, rIFN alpha, rIFN gamma, rIL-1 alpha and rIL-2 were still unable to produce cytotoxic effects on fresh human tumor cells. Treatment with monoclonal and polyclonal antibodies directed against rTNF, rLT, rIFN alpha, rIFN gamma, or rIL-1 alpha did not inhibit the cytotoxic activity of LGL-derived cytotoxic factor against fresh human tumor cells. Even a mixture of all the antibodies was incapable of blocking the cytolytic activity of the factor to fresh human tumor cells. Furthermore, intact LGL-mediated lysing of autologous tumor cells was not inhibited by any of the antibodies. These results may indicate that a cytotoxic factor produced by LGL in response to autologous tumor cells mediates lysing of fresh human tumor cells independently of TNF, LT, IFN, IL-1 and IL-2. PMID- 2106393 TI - Tissue-type plasminogen activator: intracoronary applications. AB - Intracoronary tissue-type plasminogen activator (t-PA) was employed successfully before, after, or in place of coronary artery angioplasty in four patients referred for emergency cardiac catheterization during evolving myocardial infarction. The potential roles of intracoronary thrombolysis, dose considerations for intracoronary t-PA, factors influencing the choice of plasminogen activator, and safety issues are discussed. PMID- 2106394 TI - Management of complicated coronary angioplasty by intracoronary urokinase and immediate re-angioplasty. AB - Percutaneous transluminal coronary angioplasty was complicated by acute coronary occlusion, dissection of the arterial wall, or angiographic evidence of intraluminal thrombosis in 33 high-risk patients from 153 consecutive angioplasty procedures (21.5%). Ten patients (group I) were managed with nitroglycerin (0.2 to 0.4 mg i.c.) and repeated attempts at mechanical guide wire recanalization or dilation, but they did not receive thrombolytic therapy. In the remaining 23 patients (group II), intracoronary urokinase (100,000 to 360,000 U.I.) was administered over 15-20 min after onset of coronary occlusion or thrombosis and continued during attempts at repeated dilation of the stenosis. The incidence of sudden coronary artery occlusion was 70% in group I patients and 52% in group II. The angiographic evidence of thrombus formation was observed in a higher, but not significant, proportion of group II patients (65%) as compared with group I (30%). The incidence of intimal tearing or dissection was similar in the two groups of patients (40 vs. 34.7%). The overall final success rate of the complicated angioplasty series was 48% (6/33). However, the success rate was lower (10%) in group I than in group II patients (10 vs. 65%; P less than 0.005), and the frequency of emergency coronary artery bypass grafting was lower in group II patients (13 vs. 60%; P = 0.01), suggesting that thrombolytic therapy with urokinase may be effective in the management of acute coronary occlusion and thromboembolic complications of coronary angioplasty. PMID- 2106395 TI - CO2 power-assisted hand-held syringe: better visualization during diagnostic and interventional angiography. AB - Recent technology has produced high-flow and large-lumen catheters as well as other angiographic accessories to enhance the visualization of the coronary arteries during diagnostic and percutaneous transluminal coronary angioplasty (PTCA) procedures. In spite of these technological advances, there are still many cases in which the quality of the coronary angiography could be significantly improved. This paper reports on a clinical evaluation of a hand-held power syringe. The syringe offers the ability to power inject contrast safely and effectively during routine angiograms as well as through guiding catheters with the balloon catheter present during PTCA. At the same time, control of the injection is equal to that associated with manual syringes. PMID- 2106396 TI - Cases of Neisseria gonorrhoeae with plasmid-mediated resistance to penicillin increase. The National Study Group. AB - Penicillinase-producing isolates of Neisseria gonorrhoeae (PPNG) were submitted to the National Laboratory for Sexually Transmitted Diseases for biological and genetic identification as part of an on-going national surveillance program for monitoring antibiotic-resistant gonococci. The primary identification of the isolates was completed in provincial laboratories. The isolates were documented and forwarded to LCDC through the provincial laboratories and provincial epidemiologists. Duplicate isolates from the same patient were excluded from the final analysis; retrospective clinical and epidemiological data were collected for each case. In those cases where PPNG isolates were not available for testing at LCDC, epidemiological and clinical data were included for statistical consideration. These data were collectively analyzed using computer programs developed within the National Laboratory for Sexually Transmitted Diseases. PMID- 2106397 TI - Studies on peroxidation processes of model membranes and synaptosomes: role of phosphatidic acid. AB - Dipalmitoylphosphatidic acid (DPPA) was found to exert a strong inhibitory effect on Fe-induced peroxidation of arachidonic acid inserted into liposomal dipalmitoylphosphatidylcholine (DPPC) vesicles. This inhibition was quite effective both below and above the phase transition temperature of the liposomes. Moreover, we demonstrated the antiperoxidative activity of phosphatidic acid (PA) in synaptosomal membranes. PA enriched synaptosomes were prepared by the stimulation of the endogenous phospholipase D activity or by the incubation of the synaptosomes with Streptomyces chromofuscus phospholipase D. The possible contribution of PA to the in vivo defense mechanism against free radical-induced damage is discussed. PMID- 2106398 TI - False-positive ketone tests: a bedside measure of urinary mesna. AB - The sulfhydryl mesna is increasingly used to protect the bladder and kidney from effects of chemotherapy with ifosfamide and cyclophosphamide. Mesna reacts with reagents on urinary test strips designed to detect ketones. Test-strip results were correlated to sulfhydryl concentrations in 931 urine specimens obtained after infusions of mesna. These data may be used to estimate urinary mesna concentrations at the bedside or to test compliance in outpatients given oral mesna therapy. PMID- 2106399 TI - Synthesis of lipoxygenase and epoxygenase products of arachidonic acid by normal and stenosed canine coronary arteries. AB - Coronary vascular injury promotes blood cell-vessel wall interactions that influence arachidonic acid metabolism and coronary blood flow patterns. Since lipoxygenase and cytochrome P-450 epoxygenase metabolites of arachidonic acid are synthesized by vascular and inflammatory cells and have a variety of important biological actions, we investigated the metabolism of arachidonic acid by these pathways in normal and stenosed, endothelially injured canine coronary arteries. We found and confirmed by gas chromatography/mass spectrometry that primarily 12- and 15-hydroxyeicosatetraenoic acids (HETEs) are synthesized by both coronary artery segments. Lesser amounts of 11-, 9-, 8-, and 5-HETEs are also produced. 15 Ketoeicosatetraenoic acid is also synthesized. The synthesis of 14C-HETEs is fivefold to 10-fold greater by the stenosed than the normal coronary artery. Specific radioimmunoassays indicated that the stenosed coronary artery synthesized 93 +/- 14 and 1,102 +/- 154 ng/g of tissue of 15- and 12-HETE, respectively, while the normal coronary artery produced 17 +/- 3 and 162 +/- 68 ng/g of tissue of 15- and 12-HETE, respectively. Products comigrating with 14,15 ; 11,12-; 8,9-; and 5,6-epoxyeicosatrienoic acids (EETs) and the corresponding dihydroxyeicosatrienoic acids (DHETs) were detected predominantly in stenosed coronary arteries by high-pressure liquid chromatography. The structures of the EETs were confirmed by GC/MS. The EETs and prostaglandin I2 produced endothelium independent, concentration-related relaxations of dog coronary artery rings. These data indicate that normal and stenotic coronary arteries metabolize arachidonic acid to HETEs, DHETs, and EETs along with prostaglandins; however, the synthesis of these metabolites is greater in the stenosed, endothelially injured vessel. The EETs may be synthesized during the development of cyclic flow variations and counteract the vasoconstrictor effects of thromboxane A2. PMID- 2106400 TI - Adverse hemodynamic effects of antiarrhythmic drugs in congestive heart failure. PMID- 2106401 TI - Comparative hemodynamic effects of procainamide, tocainide, and encainide in severe chronic heart failure. AB - Many of the newer antiarrhythmic agents are said to cause minimal myocardial depression, but their hemodynamic effects have not been invasively evaluated and compared in patients with severe chronic heart failure. In a randomized, crossover study, the hemodynamic responses to single oral doses of procainamide (750 mg), tocainide (600 mg), and encainide (50 mg) given to 21 patients with severe chronic heart failure were compared. Cardiac performance decreased with all three drugs, but the magnitude of deterioration differed among the three agents. Stroke volume index decreased with procainamide (-5 +/- 1 ml/m2, p less than 0.001), tocainide (-7 +/- 1 ml/m2, p less than 0.001), and encainide (-8 +/- 1 ml/m2, p less than 0.001), but the decline was significantly greater with encainide than with procainamide (p less than 0.05). Similarly, left ventricular filling pressure increased with tocainide and encainide (+4 +/- 1 and +5 +/- 2 mm Hg, respectively; both p less than 0.05), but not with procainamide; the increase was significantly greater with tocainide and encainide than with procainamide (p less than 0.001). These deleterious hemodynamic effects were accompanied by worsening symptoms of heart failure in six patients with encainide and seven patients with tocainide but in only two patients with procainamide. Serum levels for all drugs were in the therapeutic range. In conclusion, although the three type I antiarrhythmic agents tested may all adversely affect left ventricular function in patients with heart failure, encainide and tocainide are more likely than procainamide to cause hemodynamic and clinical deterioration. PMID- 2106403 TI - Intravenous thrombolytic therapy with a combination of single-chain urokinase type plasminogen activator and recombinant tissue-type plasminogen activator in acute myocardial infarction. AB - The effects of simultaneous intravenous infusions of 12 mg recombinant tissue type plasminogen activator (rt-PA) over 30 minutes and 48 mg single-chain urokinase-type plasminogen activator (scuPA) over 40 minutes were studied in 38 patients with acute myocardial infarction. Coronary arterial patency was assessed angiographically 60 minutes and 90 minutes after initiation of treatment. Patency was achieved in 19 of 31 patients (61.3%) (95% confidence limits, 42-78%) at 60 minutes and in 27 of 33 patients (81.8%) (95% confidence limits, 65-93%) at 90 minutes. Nonspecific plasminogen activation was monitored by measuring relevant plasma parameters. At 60 minutes and 120 minutes, the fibrinogen concentration decreased slightly to 82.8 +/- 24.3% and 91.2 +/- 17.4% of the preinfusion level, and the plasminogen concentration to 66.3 +/- 15.2% and 65.3 +/- 13.4%, respectively. A greater consumption of alpha 2-antiplasmin was observed, which decreased to 30.7 +/- 22.8% and 32.2 +/- 21.2% of the preinfusion level at 60 and 120 minutes, respectively. No bleeding necessitating transfusion was observed. Two patients (5.3%) died during hospitalization. The findings suggest that the combined intravenous infusion of rt-PA and scuPA at appropriate doses induces highly effective coronary thrombolysis equal to the best results obtained with either rt-PA or scuPA alone. This efficacy is coupled with high specificity. Thus, the data support the potential use of combinations of rt-PA and scuPA in place of monotherapy. PMID- 2106402 TI - Effects of desmopressin acetate on platelet aggregation, von Willebrand factor, and blood loss after cardiac surgery with extracorporeal circulation. AB - The effects of desmopressin acetate (DDAVP) on platelet aggregation and the von Willebrand factor antigen (vWF:Ag) were studied in 19 patients undergoing cardiac surgery with extracorporeal circulation. The patients represented one of five blocks in a randomized double-blind placebo-controlled parallel group trial on the effects of DDAVP on postoperative bleeding after uncomplicated coronary artery bypass operations. After termination of extra-corporeal circulation, DDAVP (0.3 microgram/kg body wt) or its vehicle was infused into a peripheral vein throughout 15 minutes. The increase in factor VIII coagulant activity after infusion did not differ between the groups but there was a significantly larger increase in vWF:Ag levels in DDAVP-treated patients. The aggregatory response to adenosine-diphosphate (ADP) and ristocetin showed a normal pattern and was not significantly different between the two groups. As compared with placebo, DDAVP did not decrease the bleeding time or the postoperative blood loss. We conclude that DDAVP causes an increase in vWF:Ag levels but does not alter platelet aggregation, bleeding time, or blood loss in uncomplicated coronary artery bypass patients. PMID- 2106404 TI - Early alterations of the baroreceptor control of heart rate in patients with acute myocardial infarction. AB - Experimental coronary occlusion is accompanied by an acute impairment of the baroreceptor-heart rate reflex. This study was planned to determine whether this impairment also occurs in humans. In 30 patients admitted to a coronary care unit for an anterior (n = 14) or inferior (n = 16) transmural myocardial infarction (MI), we measured 1) the increase in RR interval induced by stimulating carotid baroreceptors through progressive reductions in neck chamber pressure, 2) the increase in RR interval induced by stimulating arterial baroreceptors through intravenous boluses of phenylephrine, and 3) the reduction in RR interval induced by deactivating arterial baroreceptors through intravenous boluses of nitroglycerin. Measurements were performed 49.5 +/- 2.4 hours (mean +/- SEM) after the MI. The results were compared with those of five age-matched patients admitted to the coronary care unit for chest pain and found free from ischemic heart disease. The sensitivity of the carotid baroreceptor-heart rate reflex (slope of the linear regression of RR interval over neck pressure changes) was markedly less in MI than in control patients (3.8 +/- 0.5 vs. 5.9 +/- 0.6 msec/mm Hg, p less than 0.05), the reduction being similar in patients with anterior and inferior MI. This was the case also for the baroreflex sensitivity measured by the phenylephrine and the nitroglycerin methods (slope of the linear regression of RR interval over systolic blood pressure changes). However, 10.2 +/- 0.3 days later, the baroreflex sensitivity measured by all three methods increased significantly (p less than 0.05 or 0.01) and became similar to that of control subjects, which showed no significant change from the early to the late period after admission into the coronary care unit. Thus, MI is accompanied by an acute marked impairment of the baroreceptor control of the heart in humans, and this is the case both for an anterior and an inferior MI. The impairment is largely transient in nature, however, and a clear-cut recovery of the baroreflex can be seen a few days later. PMID- 2106405 TI - Acute urinary retention associated with flecainide. AB - A case of acute urinary retention, presumably secondary to the use of the antiarrhythmic drug flecainide, is presented. A mechanism for this effect is proposed based on the possibility of a local anesthetic effect on bladder mucosa. PMID- 2106406 TI - The effect of complete and incomplete revascularization on exercise variables in patients undergoing coronary angioplasty. AB - To investigate the effects of complete and incomplete revascularization on the response to exercise, 25 patients underwent symptom-limited exercise testing with continuous assessment of gas exchange a mean of 5 +/- 4 days prior to and 18 +/- 12 days following percutaneous transluminal coronary angioplasty. All antianginal medications were discontinued for testing. Revascularization was considered complete if all stenoses were reduced to less than 50% diameter (13 patients), and incomplete if one or more stenoses remained (12 patients). Consistent improvements in ST-segment depression were observed after angioplasty at matched submaximal exercise levels (mean range 0.5-0.8 mm; p less than 0.05), and were accompanied by a reduction in angina. Significant increases in heart rate and systolic blood pressure were observed at peak exercise following angioplasty in both groups. Gas exchange variables were significantly improved at maximal exercise, with a similar increase in oxygen uptake observed in both groups following angioplasty (mean increase 3.3-3.7 ml/kg/min; p less than 0.01). Thus, incomplete revascularization following coronary angioplasty resulted in hemodynamic, electrocardiographic, symptomatic, and gas exchange responses to exercise that were comparable to complete revascularization. PMID- 2106407 TI - Reversal of osmolite-warfarin interaction by changing warfarin administration time. PMID- 2106408 TI - Tissue plasminogen activator for the treatment of acute pulmonary embolism. A collaborative study by the PIOPED Investigators. AB - Thirteen patients with acute pulmonary embolism were treated in a randomized double-blind fashion either with recombinant tissue plasminogen activator (rt-PA) 40 to 80 mg, usually in combination with heparin, or with placebo plus heparin. The drug was administered intravenously over 40 to 90 minutes. Nine patients received rt-PA, and four received placebo. A lytic effect was observed 1.5 and three hours after the onset of therapy with rt-PA based upon elevated levels of fragment-D dimers. Among the patients who received rt-PA, there was a modest improvement of the total pulmonary resistance 1.5 hours after the start of therapy, but the angiograms showed no significant changes in two hours. After 24 hours, the lung scans showed a trend toward greater improvement with rt-PA, but the rate of improvement in comparison to control subjects was not statistically significant. Massive bleeding occurred in one patient. The observations in this study suggest that rt-PA has little effect in two hours on angiographic clot burden, but may produce some improvement in hemodynamics. The treatment, however, is not without risk. PMID- 2106409 TI - Natural course of treated pulmonary embolism. Evaluation by perfusion lung scintigraphy, gas exchange, and chest roentgenogram. AB - Perfusion lung scintigrams, pulmonary gas exchange data, and chest roentgenograms were obtained in 33 patients during acute embolism and over the following six months in order to assess their clinical usefulness in monitoring the effect of therapy. To this purpose, the measurement of pulmonary gas exchange and the presence of chest x-ray findings were compared with perfusion lung scintigraphic abnormalities both at diagnosis and after 7, 30, and 180 days during treatment. More than 50 percent of the pulmonary arterial tree was obstructed at diagnosis, and a large part of perfusion recovery was complete within the first month. All of the gas exchange parameters were abnormal at diagnosis, and the rate of their improvement was related to that of perfusion recovery. Interestingly, PaO2st (ie, PaO2 corrected for hyperventilation) and VE tended to return to normal during the first month as a consequence of the progressive recovery of perfusion, whereas oxygen and carbon dioxide gradients and physiologic dead space showed the persistence of some abnormalities six months after diagnosis. Significant correlations were observed between the number of ULSs evaluated on the perfusion lung scintigram (and considered an index of the severity of pulmonary embolization) and all of the gas exchange parameters at diagnosis (correlation coefficients averaged from 0.41 to 0.73) and after 7 and 30 days. The enlargement of the right descending pulmonary artery and particularly the "sausage" sign and the Westermark sign were significantly associated with a higher degree of gas exchange impairment and with a more severe embolization. In conclusion, this study demonstrates that perfusion lung scintigraphy has a primary role in monitoring the recovery of patients with pulmonary embolism under treatment. Moreover, the chest roentgenogram may help in this purpose. A second major result is that the simple measurement of some gas exchange parameters may allow the assessment of functional recovery of these patients, thus giving additional information about the effect of therapy. PMID- 2106410 TI - Intravegetation antimicrobial distribution in aortic endocarditis analyzed by computer-generated model. Implications for treatment. AB - The distribution of antibiotics into cardiac valvular tissues is incompletely understood. By integrative computer modeling, we have used previously obtained pharmacokinetic data in experimental endocarditis to characterize aminoglycoside distribution within various geographic sectors of aortic vegetations of rabbits and humans in the current study. In rabbits with pseudomonal aortic endocarditis receiving a standard regimen of amikacin (15 mg/kg every eight hours), sub-MBC levels of the drug for the infecting organism were calculated in the center of 0.38-cm vegetations; this occurred despite supra-MBC levels calculated in plasma and more peripheral loci of the vegetation. In contrast, with a high-dose regimen of amikacin (40 mg/kg every eight hours), supra-MBC drug levels were calculated throughout the entire vegetation for at least 50 percent of the dosing interval. Using similar computer-generated approaches, these data in the rabbit were approximately in simulated aminoglycoside penetration of 10-mm human aortic vegetations. Aminoglycoside regimens designed to yield supra-MBC serum levels in both normal and rapid drug eliminators consistently achieved sub-MBC levels in the center of the vegetation. Computer simulations also confirmed that daily doses of aminoglycoside at least two to four times higher than those ordinarily recommended are necessary to consistently achieve uniform supra-MBC intravegetation levels for an entire dosing interval. Such computer-generated data support the concept of maldistribution of aminoglycosides in aortic endocarditis and provide a rationale for investigating the use of high-dose regimens of aminoglycoside in treating experimental endocarditis. PMID- 2106411 TI - Reliability of pulse oximetry during exercise in pulmonary patients. AB - To evaluate the reliability of pulse oximetry during exercise, we studied 101 patients primarily with chronic pulmonary diseases. Three devices were used on different patients. Radial arterial blood was sampled at rest and maximal exercise simultaneously to pulse oximetric determination. Measured blood oxygen saturation was significantly different from noninvasive saturation at rest and also at exercise for each device. Nevertheless, changes in pulse oximetry from rest to exercise were significantly correlated with measured saturation for all three devices. Direction of changes in saturation from rest to exercise was correctly evaluated by transcutaneous oximetry in all but six instances where changes were less than 4 percent. Although measured and transcutaneous saturations are significantly different, we conclude that pulse oximetry reliably estimates changes in arterial saturation between rest and exercise for a clinical purpose. None of the three tested devices was better compared with the others in estimating saturation changes at exercise. PMID- 2106412 TI - Long-term treatment of chronic bronchitis with positive expiratory pressure mask and chest physiotherapy. AB - Long-term treatment of chronic bronchitis with chest physiotherapy with or without positive expiratory pressure (PEP) by mask was studied in 43 patients randomly allocated to PEP treatment (PEP group, 20 patients) and conventional chest physiotherapy (control group, 23 patients). After instruction, the treatments were self-administered twice daily for 12 months (34 patients) and 5 months (9 patients). Twice weekly, patients filled in a diary concerning symptoms. The PEP group had significantly less cough and less mucus production. The number of acute exacerbations were calculated from the diaries and were lower in the PEP group compared to the control group, and 85 percent of the patients in the PEP group were free from acute exacerbations versus 48 percent in the control group. The PEP group also used less antibiotics and mucolytics. The PEP group had a small increase in FEV1 of mean 62 ml compared to a small decrease of 43 ml for the control group. Treatment with a simple PEP device can reduce morbidity in patients with chronic bronchitis and may preserve lung function from a more rapid decline. PMID- 2106413 TI - Antipurified-protein-derivative antibody in tuberculous pleural effusions. AB - Using ELISA, we studied anti-PPD antibody values in 31 tuberculous and 39 carcinomatous pleural effusions. Mean ODI values of anti-PPD IgG, IgA and IgM antibodies in tuberculous pleural effusions were higher than those in carcinomatous pleural effusions (p less than 0.01 in IgG and IgA, p less than 0.05 in IgM antibodies). We also analyzed the detected antigens in PPD and BCG whole cell fraction recognized by IgG antibody in tuberculous pleural effusions. Among heteromolecular components, the antigen band from 25 to 40 Kd region was most frequently stained. This antigen was heat-stable, contained sugar components, and included no disulfide bonds. PMID- 2106414 TI - The determinants of arterial CO2 tension during weaning from mechanical ventilation. PMID- 2106415 TI - One shot of high-dose amikacin: a working hypothesis. AB - Recent information suggests that single, large daily dosages of amikacin are less nephrotoxic. The killing rate of amikacin for Escherichia coli and Pseudomonas aeruginosa also suggests to put emphasis on a high peak value. A decrease of 3 log10 CFU/ml was observed for E. coli and P. aeruginosa at 64 and 128 micrograms/ml in 20 min. In comparison, the killing rate of piperacillin was dose independent and about 6 h were required for a reduction of 10(3) CFU/ml of P. aeruginosa. In theory, the way to proceed in the future would possibly be the one shot administration of amikacin, followed by a long course of a beta-lactam antibiotic. PMID- 2106416 TI - Role of the outer membrane for quinolone resistance in enterobacteria. AB - Quinolone-resistant clones were selected from clinical Escherichia coli, Citrobacter freundii and Serratia marcescens isolates in a frequency ranging from 10(-8) to 10(-6). The outer membrane proteins of quinolone-resistant E. coli clones remained unaltered, as was the case for 10 of 11 C. freundii and 4 of 11 S. marcescens clones ('nal B' type). There was no strong relation between alterations of outer membrane proteins and cross-resistance with chemically unrelated compounds such as tetracycline or chloramphenicol; however, tetracycline resistance was observed in some C. freundii clones with unaltered outer membrane proteins ('mar A'). Most of the quinolone-resistant S. marcescens clones can be considered 'nor B' or 'nor C' mutants due to their cross-resistance with other compounds, their altered outer membrane proteins and changes of lipopolysaccharide. In a few cases, subinhibitory quinolone concentrations caused alterations of outer membrane proteins in S. marcescens during mid log phase without development of resistance. PMID- 2106417 TI - Inhibitory and bactericidal activity of cefpirome and cefotaxime against blood culture isolates. AB - Using a broth microtiter dilution method, minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) were determined for the aminothiazolyl cephalosporins cefpirome and cefotaxime against 436 blood culture isolates. At concentrations of less than or equal to 16 mg/l, cefpirome inhibited 82.3% of the isolates and cefotaxime 66.5%. At the same concentrations, cefpirome killed 60.0% of the isolates and cefotaxime 46.7%. Whereas the MIC values indicated a far better activity of cefpirome than cefotaxime against oxacillin-resistant Staphylococcus aureus, Enterococci and Pseudomonas aeruginosa, the MBC values showed a poor activity of both drugs against these strains. By comparison, cefpirome was the more active agent, covering a similar spectrum to that of cefotaxime with a slight additional activity against oxacillin-susceptible S. aureus and Staphylococcus epidermidis. PMID- 2106418 TI - A computer program for analyzing bivariate flow karyotypes. AB - This article describes a computer program for analyzing bivariate flow karyotypes of human chromosomes stained with Hoechst 33258 (HO) and chromomycin A3 (CA). The karyotype first is divided into regions that contain chromosome peaks. The chromosomes that are associated with those areas are identified. The distributions in these areas then are fitted with mathematical functions of increasing complexity. The process starts by fitting a specified number of univariate Gauss functions to projections of the HO and CA distributions of each area. The final fit can include multiple bivariate Gauss functions, including a background function for debris subtraction. The results of one stage in the fitting process serve as seed values for the next, more complex step. Since the program autonomously estimates the starting values for the iterative fitting procedures, the fit results are insensitive to operator bias and the program will consistently converge to the same solutions. The resulting table of parameter values can be used to compare flow karyotypes to a reference data set. PMID- 2106419 TI - Quantification of the DNA content of structurally abnormal X chromosomes and X chromosome aneuploidy using high resolution bivariate flow karyotyping. AB - Quantification of the Hoechst and chromomycin A3 fluorescence intensities of mitotic human chromosomes isolated from karyotypically normal and abnormal cells was performed with a dual beam flow cytometer. The resultant flow karyotypes contain information about the relative DNA content and base composition of chromosomes and their relative frequencies in the mitotic cell sample. The relative copy number of X and Y chromosomes was determined for 38 normal males and females and 6 cell lines with X or Y chromosome aneuploidy. Flow karyotype diagnoses corresponded with conventional cytogenetic results in all cases. We show that chromosome DNA content can be derived from peak position in Hoechst vs. chromomycin flow karyotypes. These values are linearly related to propidium iodide staining intensity as measured with flow cytometry and to the binding of gallocyanin chrome alum to phosphate groups as measured with slide-based scanning photometry. Cell lines with deleted or dicentric X chromosomes ranging in length from 0.53 to 1.95 times normal were analyzed by using flow cytometry. The measured difference in DNA content between a normal X and each of the structurally abnormal chromosomes was linearly correlated to the difference predicted from cytogenetics and/or probe analyses. Deletions of 3-5 Mb, which were at and below the detection limits of conventional cytogenetics, could be quantified by flow karyotyping in individuals with X-linked diseases such as Duchenne muscular dystrophy, choroideremia, and ocular albinism/ichthyosis. The results show that the use of flow karyotyping to quantify the size of restricted regions of the genome can complement conventional cytogenetics and other physical mapping techniques in the study of genetic disorders. PMID- 2106420 TI - Study of X chromosome abnormality in XX males using bivariate flow karyotype analysis and flow sorted dot blots. AB - We have used bivariate flow karyotype analysis to quantify aberrant X chromosome size in 11 XX males. With one exception, the patients could be grouped into those with an X homologue difference greater than normal (Group A, n = 3) and into those whose X homologue difference could not be distinguished from female controls (Group B, n = 7). The range of sizes of the aberrant X chromosome in Y sequence positive patients agrees with the variable nature of the X-Y interchange in these individuals as determined by the use of Y-specific DNA probes and Southern blotting analysis. In one patient it was possible to sort separately the normal and the X-Y interchanged homologues for dot blot analysis. The presence of Y sequences and an increased dose of the zinc finger gene, ZFY, were detected in the X-Y interchanged homologue. In preliminary studies of 5 male and 6 female controls, it was noted that a consistent difference between the two X homologues in females was found which could not be totally explained by errors of the fitting procedure. We suggest that this difference could be due to X inactivation and that the two X homologues in females might be distinguishable. PMID- 2106421 TI - Multivariate chromosome analysis and complete karyotyping using dual labeling and fluorescence digital imaging microscopy. AB - The combination of multiple dye-DNA interactions, a fluorescence digital imaging system with a scientific CCD camera, and multivariate image analysis allows the rapid karyotyping of fluorescent human metaphase chromosome spreads. Chromosomes are stained with the bisbenzimidazole dye Hoechst 33342 and chromomycin A3, a dye pair used frequently in bivariate flow analysis and sorting of metaphase chromosomes in suspension. The use of ratio functions involving the total and peak intensities of the two dyes provides increased resolution of the karyotype in the microscope, and it can be anticipated that the same approach could lead to improved performance with flow systems as well. High pass filtering with a Laplace operator yields characteristic banded images of the individual chromosomes, even with total fields that are less than 200 pixels on a side. PMID- 2106422 TI - Adaptation of jejunal to colonic mucosal autografts in experimentally induced short bowel syndrome. AB - The behavior of jejunal to colonic mucosal autografts was studied in an experimental animal model of short bowel syndrome (SBS). Histological appearances, enterocyte enzyme activities, and in vitro glucose transport were studied at the donor and recipient graft sites in control, short-bowel syndrome, and gastrocolic fistula 5-week-old Sprague-Dawley rats. Small intestinal function was maintained in the jejunocolonic graft after 80% small bowel resection; animals in which small bowel was not resected showed loss of graft function and enzyme activity. This effect is dependent on the presence of jejunal chyme: after gastrocolic fistulae, the jejunum to colon grafts lost jejunal functional activities. Total parenteral nutrition did not alter graft behavior but improved the postoperative mortality of the procedures. The results provide additional information on intestinal adaptation in SBS. PMID- 2106423 TI - Divergent cardiac effects of the first and second generation hypoglycemic sulfonylurea compounds. AB - The effects of first and second generation hypoglycemic sulfonylureas on the incidence of ventricular ectopic beats and on the duration of transitional ventricular fibrillation in the ischemic rat heart were investigated. First generation sulfonylurea compounds (tolbutamide, carbutamide and gliclazide) in 105 preparations increased, while second generation sulfonylurea compounds (glibenclamide and glipizide) in 50 preparations decreased in a dose-dependent manner both the number of ventricular ectopic beats and the duration of transitional ventricular fibrillation during the first 30 min after ligation of the left anterior descending coronary artery. Therefore, second generation sulfonylureas should be preferred in the treatment of type 2 diabetics with ischemic heart diseases, if satisfactory metabolic control cannot be achieved by a treatment regimen and diet alone. PMID- 2106424 TI - Modification of prostacyclin-stimulatory activity in sera by glucose, insulin, low density lipoprotein, linoleic acid and linoleic acid hydroperoxide. AB - Reduced prostacyclin (PGI2) production by the vascular wall has been proposed as one of the possible causes of diabetic vascular complications. We found an activity which stimulated PGI2 production by cultured endothelial cells (PGI2 stimulatory activity, PSA) in human plasma-derived serum (PDS). The PSA was less in patients with diabetes mellitus. The present study was undertaken to evaluate how metabolic factors relevant to diabetic angiopathy modify the PSA. Pooled PDS was prepared from 10 healthy volunteers. The 6-keto-PGF1 alpha (6KF, a stable metabolite of PGI2) production by cultured bovine aortic endothelial cells was maximally stimulated by Dulbecco's modified Eagle's medium (DMEM) containing 10% pooled PDS after incubation for 60 min. The production of 6KF was reduced in a dose-dependent manner by the addition of 10% pooled PDS with glucose and linoleic acid hydroperoxide (lipid peroxide). In contrast, human low density lipoprotein (LDL) and linoleic acid (unsaturated fatty acid) enhanced the production of 6KF by 10% pooled PDS in a dose-dependent manner. Insulin, however, showed no effect on the production of 6KF by 10% pooled PDS. These results suggest that the reduced PSA in diabetics may be the result, in part, of a modification of the PSA by diabetic metabolic factors such as glucose and lipid peroxide. PMID- 2106425 TI - Lack of favorable effect of immunomodulators on outbred syngeneic rodent islet transplantation. AB - We studied the effect of two immunomodulators, lobenzarit disodium and OK-432, on outbred syngeneic islet transplantation. Six hundred fresh islets taken from two male Wistar rats were transplanted intraportally into other male Wistar rats that had been made diabetic with streptozotocin. Lobenzarit was given to 12 recipients and OK-432 to seven recipients intraperitoneally for 1 month, while nine controls received only intraperitoneal saline. Both drug-treated groups could not maintain lower fasting plasma glucose levels or higher fasting body weights at each time as compared with controls. The islet survival time in lobenzarit-treated (23.5 +/ 8.0 days) and OK-432-treated (25.3 +/- 13.4 days) groups was not longer than that (21.6 +/- 9.4 days) of the control group. All the pancreatic insulin contents of the seven surviving controls, ten surviving lobenzarit and five surviving OK-432 recipients were less than 0.8% of the mean insulin content obtained from 12 normal male rats. The hepatic insulin content of both drug treated groups was not higher than that of the control group. These results suggest that lobenzarit disodium and OK-432 cannot protect outbred syngeneic islet grafts. PMID- 2106426 TI - [The hepatitis C virus]. PMID- 2106427 TI - [Behcet's syndrome: treatment with recombinant interferon gamma]. PMID- 2106428 TI - [Blood transfusion and hepatitis: hepatitis C virus detection]. PMID- 2106429 TI - Estrogen modulated gonadotropin release in relation to gonadotropin-releasing hormone (GnRH) and phorbol ester (PMA) actions in superfused rat pituitary cells. AB - The involvement of protein kinase C (PKC) in GnRH action is still a matter of controversy. We have conducted a comparative study of LH and FSH release in response to GnRH and to phorbol ester myristate acetate (PMA), an activator of PKC, by rat pituitary cells maintained in culture. The effect of E2 pretreatment coupled or not with PKC depletion was also studied. Different kinetics in the response of LH and FSH to GnRH were observed, suggesting that the intracellular pathways involved in the release process of the two hormones were somewhat different. Moreover, PMA (10 nM) stimulated LH release greatly and FSH release only slightly. Intracellular PKC depletion, obtained by a prolonged treatment (18 h) of the cells with PMA (1 microM), produced different results according to the endocrine status of the pituitary cells. GnRH (10 nM)-induced LH release was significantly decreased in PKC-depleted cells from proestrous females. For PKC depleted cells from OVX females, it was decreased significantly only when cells had been pretreated by E2. These results suggest that the modulation of LH secretion by E2 involves PKC activation. FSH release was poorly stimulated by PMA; but, under any conditions, PKC depletion did not affect GnRH-induced FSH release. PMID- 2106430 TI - Leukemia inhibitory factor: a novel bone-active cytokine. AB - A number of cytokines have been found to be potent regulators of bone resorption and to share the properties originally attributed to osteoclast-activating factor. One such activity, differentiation-inducing factor (DIF, D-factor) from mouse spleen cells, shares a number of biological and biochemical properties with the recently characterized and cloned leukemia inhibitory factor (LIF). We have assessed the effects of recombinant LIF on bone resorption and other parameters in neonatal mouse calvaria. Both recombinant murine and human (h) LIFs stimulated 45Ca release from prelabeled calvaria in a dose-dependent manner. The increase in bone resorption was associated with an increase in the number of osteoclasts per mm2 bone. The osteolytic effect of hLIF were blocked by 10(-7) M indomethacin. hLIF also stimulated incorporation of [3H] thymidine into calvaria, but the dose response relationship was distinct from that for bone resorption, and this effect was not blocked by indomethacin. Similarly, hLIF increased [3H]phenylalanine incorporation into calvaria, and this was also not inhibited by indomethacin. It is concluded that LIF stimulates bone resorption by a mechanism involving prostaglandin production, but that a distinct mechanism is responsible for its stimulation of DNA and protein synthesis. The primary structure of LIF differs from that of other fully characterized, bone-active cytokines, and it, thus, represents a novel factor which may be involved in the normal regulation of bone cell function. PMID- 2106431 TI - A nonoxytocinergic prolactin releasing factor and a nondopaminergic prolactin inhibiting factor in bovine neurointermediate lobe extracts: in vitro and in vivo studies. AB - Several peptidergic PRL-releasing factors (PRFs) have been described; however, none have been proven to be of primary physiological importance in the control of hormone release. Similarly dopamine withdrawal alone cannot completely explain the profiles of PRL secretion observed under a variety of conditions. We describe here the isolation in semipurified form of both a PRF and a PRL-inhibiting factor (PIF) from bovine neurointermediate lobe (NIL) extracts. Acid extracts of bovine NILs stimulated, in a dose-related manner, PRL release from cultured anterior pituitary cells, even after immunoabsorption of endogenous oxytocin from the extract. PIF and PRF activities were semipurified from NIL extracts by Sephadex chromatography and detected by in vitro and in vitro bioassays. The PRF material could be separated from oxytocin by gel sieving and was active in the presence of dopamine in vitro unlike synthetic oxytocin and in cell preparations in which the oxytocin-responsive lactotrophs had been removed by selective cytotoxin cell targeting using an oxytocin-ricin A chain cytotoxic conjugate. The PRF material stimulated PRL secretion in a dose-dependent fashion in conscious male rats after iv injection. The PIF material comigrated on sizing gel chromatography with immunoreactive oxytocin and was active in vitro during dopamine blockade with domperidone and in vivo in the presence of endogenous dopaminergic tone. These data suggest that novel factors present in the NIL might exert physiologically relevant control over lactotroph function and add to the growing literature on the presence of a PRF in the NIL. PMID- 2106432 TI - Sphingosine interacts directly with the receptor complex to inhibit thyrotropin releasing hormone binding. AB - Sphingosine inhibition of [3H] [N3-Me-His] TRH (MeTRH) binding, previously shown to be independent of its effects on protein kinase-C, has been further characterized in GH3 cell membranes and in a partially purified, digitonin solubilized receptor preparation. In membranes, as in intact cells, sphingosine inhibited [3H]MeTRH binding by decreasing receptor affinity, but, in contrast to its effect in intact cells, did not affect the number of available binding sites. The inhibition of binding was linear up to 75 microM sphingosine (in the presence of 100 microM BSA at 0.1 mg membrane protein/ml), yielding an apparent Ki of 51 microM. Since GTP decreases the affinity for MeTRH binding in GH3 cell membranes, we studied interactions between GTP and sphingosine. While the effects of low concentrations of GTP gamma S and sphingosine were additive, sphingosine inhibition of MeTRH binding surpassed and was not affected by the addition of maximally inhibitory concentrations of GTP gamma S. Also, sphingosine (75 microM) did not affect the ability of a maximally effective dose of TRH to stimulate the low Km GTPase (vehicle, +35 +/- 5%; sphingosine, +32 +/- 10%); there was a 25% decrease in total GTPase activity in the presence of sphingosine. MeTRH binding to digitonin-solubilized receptors, which had properties similar to those described previously by others, including no effect of GTP on binding, was inhibited by sphingosine. In solubilized receptors, as in membranes, sphingosine caused a decrease in apparent affinity without changes in the number of binding sites. These data suggest that sphingosine interacts directly with the TRH receptor [or an associated factor(s) in the receptor complex] to decrease affinity by a mechanism that does not involve uncoupling of G-proteins. PMID- 2106434 TI - Luteinizing hormone-releasing hormone neurons express c-fos antigen after steroid activation. AB - Immature female rats received implants containing 17 beta-estradiol on postnatal day 28 at 0900 h, followed 24 h later by either blank capsules or progesterone. Between 1500-1600 h on the day of progesterone (or blank capsule) implantation, these rats, a group of unoperated or sham controls, and a group of estrogen progesterone-treated immature male rats were killed and perfused, and their brains processed for immunocytochemistry of c-fos antigen and LHRH. LHRH neurons consistently expressed c-fos after estrogen-progesterone treatment in females but not males; in only one of four females examined was c-fos induced after estrogen treatment. No fos was associated with LHRH neurons in the control groups. The LHRH neurons that expressed c-fos were located in the preoptic area and anterior hypothalamus; more rostral LHRH cells did not appear stimulated. These data demonstrate that gonadal steroids, administered in a paradigm that predictably produces timed stimulation of LH release, induce c-fos in LHRH neurons. The induction of c-fos in LHRH neurons provides a potentially useful and powerful tool for studying LHRH activation at the cellular level. PMID- 2106433 TI - Involvement of distinct G-proteins in the action of vasopressin on rat glomerulosa cells. AB - We have previously shown that vasopressin (VP) induces breakdown of membrane phosphoinositides in adrenal glomerulosa cells. In the present study we demonstrate that the accumulation of inositol phosphates (IP) measured in the presence of arginine vasopressin (AVP) is reduced if the cells are incubated in a calcium-free medium. This effect cannot be accounted for by modification of VP binding, reduction of inositol lipid labeling, or stimulation of inositol, 1,4,5, triphosphate 5-monophosphatase. It mainly affects phospholipase-C activity, since this enzyme is highly sensitive to calcium. Ionomycine and nifedipine, which, respectively, increase and decrease the intracellular calcium concentration, also, respectively, stimulate and inhibit IP accumulation. In membranes prepared from pertussis toxin (IAP)-treated cells, AVP stimulates inositol monophosphate accumulation to the same extent as in membranes derived from untreated cells. However, in intact cells, IAP decreases the inositol monophosphate accumulation. This decrease probably involves calcium influx, since we show that AVP stimulates a unidirectional calcium influx, which is completely blocked by IAP treatment. In rat adrenal glomerulosa cells, the AVP-stimulated secretion of aldosterone is mainly under the control of calcium, since a full inhibition of its secretion is observed under conditions in which the calcium influxes are completely suppressed despite a sustained accumulation of IP (calcium depletion or IAP treatment). Together, these results signify that VP acts on rat glomerulosa cells by two distinct mechanisms: calcium influx, which is IAP sensitive, and phosphoinositide turnover, which is IAP insensitive. PMID- 2106435 TI - Rat granulosa cells express transforming growth factor-beta type 2 messenger ribonucleic acid which is regulatable by follicle-stimulating hormone in vitro. AB - Freshly harvested granulosa cells (GC) from diethylstilbestrol (DES)-treated rats were examined for the presence of transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 2 mRNA by Northern analysis. TGF-beta 1 mRNA was not detectable, but hybridization of total RNA with a radiolabeled TGF-beta 2 cDNA probe revealed two mRNA species (5.1 and 3.6 kb) indicative of TGF-beta 2 mRNA. In response to FSH (50 ng/ml), relative TGF-beta 2 mRNA concentrations in cultured GC were 54% of control levels. Furthermore, the conditioned culture medium from FSH-treated GC contained significantly lower (p less than 0.01) TGF-beta-like activity relative to controls. These results demonstrate that rat GC express TGF-beta 2 mRNA which is regulatable by FSH in vitro. PMID- 2106436 TI - Sclerotherapy of bleeding esophageal varices in schistosomiasis. Comparative study in patients with and without previous surgery for portal hypertension. AB - Ninety-seven patients with bleeding esophageal varices due to mansonic schistosomiasis were treated with endoscopic sclerotherapy. Seventy-five patients (Group I) had previously undergone surgery for portal hypertension and presented with bleeding recurrence. Twenty-two patients (Group II) had not undergone surgical treatment. The sclerotherapy technique employed was intravascular (IV) injections of ethanolamine in 40 patients and paravascular (PV) in 57 patients. Of a total of 38 (39%) patients who had bleeding recurrence, 27 (36%) were from Group I and 11 (50%) from Group II (p less than 0.005). Over a follow-up period of 48 to 132 months, 367 sessions of sclerotherapy were carried out in the 72 remaining patients from Group I (4.93 +/- 2.05). The remaining 16 patients from Group II needed 121 (7.56 +/- 2.70) sessions of sclerotherapy (p less than 0.001). Thus, sclerotherapy was effective in the control of rebleeding in 73 (97.3%) patients from Group I and 16 (72.7%) from Group II (p less than 0.05). We conclude that previous surgical treatment for portal hypertension in patients with mansonic schistosomiasis, greatly benefits treatment of rebleeding esophageal varices by endoscopic sclerotherapy. This is probably due to the lower portal pressure after splenectomy. PMID- 2106437 TI - Adaptive response induction by bacterial catalysis of nitrosation. PMID- 2106438 TI - The increasing problem of young adults with congenital heart disease. PMID- 2106439 TI - Reproducibility of cardiopulmonary parameters during exercise in patients with chronic cardiac failure. The need for a preliminary test. AB - To examine the reproducibility of cardiopulmonary exercise testing in patients with heart failure, three consecutive tests were performed in 30 such patients. The first test underestimated treadmill exercise time by about 20% when compared with the second and third tests, which were not significantly different. Peak achieved VO2, VCO2 and VE were also less during the first test, but blood pressure, heart rate and respiratory rate responses were similar in the three tests. When cardiopulmonary exercise tests are used to assess functional capacity in either individual patients or groups (as in a therapeutic trial), at least two tests should be performed, as a single test is likely to underestimate exercise capacity. PMID- 2106440 TI - Immunodeficient mice recover from infection with vaccinia virus expressing interferon-gamma. AB - Recombinant vaccinia viruses (VV)-encoding murine interferon-gamma (IFN-gamma) were constructed and the effect of virus-encoded IFN-gamma on the immune response towards VV in vivo investigated. In athymic nude mice and sublethally irradiated euthymic mice, IFN-gamma expression by VV enabled the mice to recover from the infection, whereas mice infected with the control virus died. In normal CBA/H mice also, the growth of VV was greatly reduced and it was cleared faster from mouse organs than the control virus. Natural killer (NK) cell responses in these mice were not enhanced suggesting that this recovery is not NK cell mediated. Other possible mechanisms and implications of this observation are discussed. PMID- 2106441 TI - Reconstitution of H-2 class I expression by gene transfection decreases susceptibility to natural killer cells of an EL4 class I loss variant. AB - Several reports have suggested that an inverse correlation exists between major histocompatibility complex class I expression and the susceptibility to natural killer (NK)-mediated lysis. For example, the increased class I expression induced by interferon-gamma was always accompanied by an increased resistance to NK lysis. Likewise, class I loss variants were often more NK susceptible than their normal counterparts. To investigate whether the inverse correlation between class I expression and NK susceptibility was fortuitous or whether the class I molecules were directly responsible for this effect we resorted to gene transfection studies. From the murine thymoma line EL4 and H-2Db- and Kb-negative variant S3 was selected. This variant was highly susceptible to NK lysis. S3 was found to have a defect in beta 2-microglobulin gene expression. Therefore, restoration of Db and Kb expression could be achieved by transfection with the beta 2-microglobulin gene. This resulted in a strong decrease in susceptibility to NK lysis to the level of the H-2+ parental EL4. Transfection with class II genes had no effect. Blocking of the class I molecules on the H-2+ cells with anti-H-2b F(ab')2 fragments increased the susceptibility to NK cells to the level of the H-2- variant S3. These data demonstrate that the class I molecules on the targets are directly responsible for regulation of NK susceptibility but the mechanism is not clear. Possibly the class I molecules interfere with the unknown NK target structures. PMID- 2106442 TI - Detection of primary cytotoxic T lymphocytes specific for the envelope glycoprotein of HIV-1 by deletion of the env amino-terminal signal sequence. AB - A heterogenous population of envelope glycoprotein-specific cytotoxic effector cells are found in the peripheral blood of individuals infected with HIV-1, and in many cases env-specific lysis is not restricted by MHC molecules and is not blocked by antibody to CD3 (Riviere, Y. et al., J. Virol. 1989, 63:2270). In order to detect env-specific cytotoxic T lymphocytes (CTL) in fresh peripheral blood mononuclear cells of HIV-1-infected donors, a mutant env gene with deletion of the amino-terminal signal sequence was inserted into vaccinia virus. This deletion of the amino-terminal signal sequence was inserted into vaccinia virus. This deletion results in synthesis of an envelope protein that is not glycosylated and not expressed at the surface of infected cells. Target cells infected with this recombinant vaccinia virus are not lysed by antibody-mediated cellular cytotoxicity, but they are recognized by secondary CTL. Comparing lysis of target cells expressing gp160 of HIV-1 and the signal peptide deletion mutant, primary env-specific CTL were detected in some individuals infected with HIV-1. PMID- 2106443 TI - Bacteriological quality of on-farm manufactured goat cheese. AB - The bacteriological quality of 198 ripened soft or semi-soft goat cheeses obtained from dairy farms and the retail trade was investigated. The cheeses were examined for total counts of aerobic bacteria, coliform bacteria (37 and 44 degrees C respectively), enterococci, coagulase positive staphylococci, Bacillus cereus and Clostridium perfringens. Cheeses obtained from dairy-farms were also determined for pH value. In terms of all tests performed, cheeses made of heat treated milk with starter culture had the best prospects for fulfilling the criteria for 'fit for consumption'. Cheeses made of raw milk without starter culture made up the most unsatisfactory group from a food-hygiene point of view. Bacteriological guidelines for on-farm manufactured goat cheese are suggested. PMID- 2106444 TI - Alterations in levels of mRNAs coding for neurofilament protein subunits during regeneration. AB - Animal models of neuronal injury can be used to explore mechanisms that regulate the expression of genes coding for cytoskeletal proteins and transmitter-related markers. In the present study, in situ hybridization was used to measure levels of messenger ribonucleic acid (mRNA) encoding each of the neurofilament subunits and beta-tubulin in spinal motor neurons at intervals (4 to 56 days) following a unilateral crush of the sciatic nerve. Levels of beta-tubulin mRNA increased (approximately twofold), peaked at 28 days postaxotomy, and returned to control values by 56 days postaxotomy. In contrast, levels of mRNA encoding neurofilament subunits were reduced and returned to control values at 56 days following the lesion. There were significant differences among relative levels of mRNAs coding for each subunit. Other studies have demonstrated that the ratio of pulse-labeled neurofilament subunits in motor axons remained unaltered during regeneration. Therefore, the ratios of neurofilament subunits in axons must be regulated at one of the steps that intervenes between the control of levels of mRNA and the anterograde axonal transport of assembled neurofilaments. PMID- 2106445 TI - Induction of c-fos mRNA and protein in neurons and glia after traumatic brain injury: pharmacological characterization. AB - Focal brain injury in mice induced c-fos mRNA and protein in neurons throughout the damaged neocortex, including the piriform and the entorhinal cortices, as well as in nonneural brain cells (e.g., glia, pia, ependyma). The pattern of c fos induction after injury suggested that injury led to spreading depression which then led to c-fos induction in neurons. Human neurons in the temporal cortex and hippocampus also showed c-fos protein induction after neurosurgical trauma. The c-fos mRNA and protein induction in mouse neurons was prevented by the noncompetitive NMDA antagonist ketamine but only partially inhibited by the voltage-dependent calcium channel antagonist nifedipine and the calmodulin antagonist trifluoperazine. The c-fos protein induction in nonneural brain cells after injury was not affected by these drugs. Thus, induction of c-fos in neocortical neurons after focal brain injury is partly NMDA receptor mediated. PMID- 2106446 TI - Ultrastructural effects of Nifurtimox on rat adrenal cortex related to reductive biotransformation. AB - Nifurtimox (Nfx) (4(5-nitrofurfurylidene)amino)-3-methylthiomorpholine-1, 1 dioxide) is a drug used against Chagas' disease, a parasitic sickness afflicting several million Latin Americans. Nfx administration to Sprague-Dawley male rats (220-250 g) at a dose of 100 mg/kg caused pronounced alterations in the adrenal cortex involving the fasciculata and reticularis zones but which were not evident in the glomerulosa. Alterations observed involved mitochondria, nuclei, Golgi apparatus, and the endoplasmic reticulum but were more intense in the mitochondria. There is Nfx nitroreductase activity in the adrenal microsomal, mitochondrial, and cytosolic-rich fractions but most of it is in the mitochondrial-rich fraction. Activity in the first two fractions requires NADPH and that in the cytosol is only observed in the presence of hypoxanthine as substrate. Enzymatic activity in all fractions is inhibited by oxygen. CO does not inhibit mitochondrial Nfx nitroreductase and inhibits only 10% of the microsomal enzyme activity. Hypoxanthine-dependent cytosolic activity is inhibited by allopurinol. Present results suggest that Nfx is activated to damage producing reactive metabolites by nitroreductive biotransformation in rat adrenal organelles. Mitochondrial and microsomal bioactivation would occur at the level of the flavoenzyme P-450 reductase rather than at P-450 itself, and cytosolic bioactivation would be mediated by xanthine oxidase. Epidemiological studies on adrenal function in patients undergoing Nfx treatment would be necessary to establish the potential toxicological relevance of these findings. PMID- 2106447 TI - Philadelphia chromosome-negative acute hematopoietic malignancy: ultrastructural, cytochemical and immunocytochemical evidence of mast cell and basophil differentiation. PMID- 2106448 TI - Estrogen synthetase in the horse. Comparison of equine placental and rat liver NADPH-cytrochrome c (P-450) reductase activities. AB - NADPH-cytochrome c (P-450) reductases from horse placenta and rat liver were purified and their biological activities compared using cytochrome c as substrate. Rat liver reductase was purified to electrophoretic homogeneity in one chromatographic step on 2',5'-ADP agarose, and had a relative mass of 85,000 Da as estimated by SDS-PAGE. Equine placental reductase was separated from cytochrome P-450 on aminohexyl-Sepharose 4B and further purified on 2',5-ADP agarose; this preparation exhibited two bands, one of 85,000 and one of 80,000 Da, on SDS-PAGE. The lower molecular weight form was assumed to be a proteolytic product of the higher molecular weight form. A high retention of activity was obtained in both preparations. Equine placenta and rat liver enzymes were found to exhibit very similar Vmax and Km, suggesting that they are not species specific. PMID- 2106449 TI - Comparison of urinary human follicle-stimulating hormone and human menopausal gonadotropin for ovarian stimulation in polycystic ovarian syndrome. AB - A randomized, double-blind, crossover study was carried out to compare purified urinary follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) for ovarian stimulation in polycystic ovarian syndrome (PCOS). Twelve patients were stimulated with FSH and hMG in three alternate cycles. FSH, luteinizing hormone (LH), estradiol, dihydroepiandrosterone sulphate, free and total testosterone, delta 5-androstenedione, sex hormone binding globulin, and ovarian volume were monitored during the stimulation. There was no difference between the dose of FSH and hMG necessary to induce preovulatory follicles in the individual patients. The mean increase of ovarian volume during stimulation with FSH and hMG was 120% and 129% respectively (no significant difference). Two patients became pregnant in the first cycle. Two other patients had delayed bleeding and positive serum-human chorionic gonadotropin. No significant difference was found in the endocrine changes during the two different stimulation methods. The LH/FSH ratio was normalized after a few days of treatment regardless of the type of stimulation. The size of the material does not permit a comparison of the efficacy of the two treatment schedules. Our clinical and ultrasonic observations do not support the theory that treatment of infertility in PCOS with FSH is more safe than with hMG. PMID- 2106450 TI - Can growth hormone increase, after clonidine administration, predict the dose of human menopausal hormone needed for induction of ovulation? AB - Recent observations claimed that growth hormone (GH) administration increased the sensitivity of the ovary to gonadotropin stimulation. These findings prompted us to assess whether ovarian response to human menopausal gonadotropin (hMG) is correlated to GH reserve. Before hMG administration, 25 patients were tested for GH reserve by administration of clonidine. Of the 25 patients, 8 showed a significant increase in GH (9.2 +/- 4.5 ng/mL) and needed a significantly lower dose of hMG/human chorionic gonadotropin to elicit a good ovarian response than the 17 patients who did not respond to clonidine administration may help to estimate the initial dose range of hMG necessary for induction of ovulation. PMID- 2106451 TI - Increasing the human menopausal gonadotropin dose--does the response really improve? AB - This study assesses the effects of attempts to optimize human menopausal gonadotropin (hMG) dosage in 271 patients who had at least two hyperstimulation cycles for in vitro fertilization or gamete intrafallopian transfer. In the first cycle, all patients received clomiphene citrate and hMG 150 IU/d. In the second cycle, the hMG dose was increased in 45% of patients to try to increase the egg yield. In spite of the increase, the population response was practically identical in both cycles. Median numbers of eggs retrieved (6 versus 6), no eggs retrieved (0.4% versus 1%), only one or two eggs retrieved (10% versus 10%), and canceled cycles (10% versus 10.7%). This suggests that increasing the hMG dosage above 150 IU does not increase the number of eggs retrieved. A poor response may be due to inherent differences in follicular development that cannot be overcome by increases in hMG dosage. PMID- 2106452 TI - Clinical pharmacodynamics of urinary follicle-stimulating hormone and its application for pharmacokinetic simulation program. AB - To clarify the pharmacodynamics of urinary gonadotropins, same doses of Metrodin (Serono Laboratories, Aubonne, Switzerland) or Pergonal (Serono, Rome, Italy) were injected intramuscularly into normal adult men in a crossover manner, and serum follicle-stimulating hormone (FSH) and luteinizing hormone were measured by radioimmunoassay. Follicle-stimulating hormone bioavailability parameters of Metrodin (150 IU), such as peak concentration (cmax), the time when cmax is observed, half-life, and area under concentration, were 8.9 +/- 2.5 mIU/mL, 7.7 +/- 2.1 hours, 36.0 +/- 16.4 hours, and 258.6 +/- 47.9 mIU/mL X hour, respectively, and were not statistically different from those of Pergonal. On the other hand, by daily administration of Metrodin into women with isolated gonadotropin deficiency, serum FSH levels were elevated gradually, reached peak levels within 4 days, and maintained the same levels until the doses were increased. This pattern of FSH accumulation was parallel with the simulation pattern calculated using bioavailability parameters obtained from normal men, suggesting that exogenously administered FSH distributes into peripheral circulation in the manner of a one compartment model. PMID- 2106453 TI - Comparative trial of luteinizing hormone-releasing hormone analog/human menopausal gonadotropin and clomiphene citrate/human menopausal gonadotropin in an assisted conception program. AB - To establish the usefulness of a new drug regimen in an assisted conception program, a trial was performed comparing clomiphene citrate (CC) plus human menopausal gonadotropins (hMG) with a new regimen of intranasal luteinizing hormone-releasing hormone (LH-RH) analog plus hMG. One hundred two patient cycles received treatment with CC and hMG and 118 patient cycles received treatment with LH-RH analog and hMG. Fifteen percent of cycles were canceled in the CC group and 8% in the analog group. Four percent of cycles in the CC group were canceled due to premature ovulation. The number of oocytes collected in the analog group was significantly higher than in the CC group (8.5 versus 5.5), as was the number of mature oocytes (3.5 versus 2.7). However, the percentage of mature oocytes was higher in the CC group (54.2% versus 42.3%). The number of embryos resulting from in vitro fertilization as well as the number of cleaving embryos were significantly higher in the analog group (5.2 versus 2.8 and 4.6 versus 2.3, respectively). The pregnancy rate in the analog group was significantly higher than in the CC group (30.6% versus 16.1%), as was the live birth rate (21% versus 8%). Early pregnancy loss was significantly higher in the CC group than in the analog group (35% versus 9%); and the serum level of LH on the day of human chorionic gonadotropin (hCG) administration was also significantly elevated in the CC group when compared with the analog group (8.1 versus 4.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106454 TI - Comparison of different regimens of a gonadotropin-releasing hormone analog during ovarian stimulation for in vitro fertilization. AB - Three treatment protocols were used in 156 in vitro fertilization cycles. Leuprolide acetate was begun on day 1 of the cycle in one group (n = 20), on day 3 in another (n = 48), and the third control group (n = 88) did not receive the gonadotropin-releasing hormone analog. Human menopausal gonadotropin was initiated on day 3 in all groups. Peak estradiol (E2) levels and the mean numbers of mature oocytes and embryos transferred per cycle were significantly greater in the day 3 group than in either the day 1 or control groups. Patients who received the day 3 protocol had significantly fewer cancelled cycles. A decline in E2 was observed on the third day of analog administration in certain patients, particularly those on the day 1 protocol. Follicle-stimulating hormone and luteinizing hormone (LH) levels increased two- to fivefold 24 hours after initiation of the analog. Thereafter the gonadotropin levels fell, but nevertheless remained above those of controls for most of the cycle. Hence, it appears that enhanced follicular growth attributed to the early transient rises in gonadotropins can be coupled to a suppression of endogenous LH surges in leuprolide-treated women. These beneficial effects seem to be more likely to occur if leuprolide is initiated on cycle day 3 rather than day 1. PMID- 2106455 TI - High-dose follicle-stimulating hormone stimulation at the onset of the menstrual cycle does not improve the in vitro fertilization outcome in low-responder patients. AB - In an attempt to improve their outcome with in vitro fertilization (IVF), 34 low responder patients were stimulated with six ampules of follicle-stimulating hormone (FSH) daily starting on day 1 (n = 17) or day 2 (n = 17) of their menstrual cycles. The stimulated cycles showed a mean peak estradiol of 443 +/- 173 pg/mL, mean days of human chorionic gonadotropin of 7.6 +/- 1.4, 2.67 +/- 1.5 preovulatory oocytes per retrieval, and 2.56 +/- 1.3 oocytes per transfer. Three clinical pregnancies resulted after 25 embryo transfer cycles (12%). With paired analysis, we compared 8 patient cycles with prior six ampules of FSH stimulation starting on day 3; all parameters examined showed no significant differences. In a comparison of 22 patient cycles with prior 4 ampules of FSH stimulation on cycle day 3, no significant differences in any parameters were observed except in the higher number of ampules used in the present study. We conclude that high dose FSH stimulation at the onset of the menstrual cycle does not improve the IVF outcome in low-responder patients. PMID- 2106456 TI - Severe ovarian hyperstimulation syndrome using agonists of gonadotropin-releasing hormone for in vitro fertilization: a European series and a proposal for prevention. AB - Severe ovarian hyperstimulation syndrome (OHSS) was recorded in 8 of 413 patients after the use of gonadotropin-releasing hormone agonists (GnRH-a) associated with gonadotropins for in vitro fertilization. Seven of the 8 patients were pregnant. Common factors associated with the development of OHSS were high serum estradiol values on the day of ovulation induction and many follicles greater than or equal to 12 mm. Based on this experience, a new therapeutic schedule was used in a group of 10 patients who, after GnRH-a and gonadotropin stimulation, were judged to be at high risk of OHSS on the day of human chorionic gonadotropin (hCG). No hCG was administered and gonadotropins were stopped. The administration of GnRH-a was continued and, after a further period of pituitary desensitization, follicular stimulation was recommended with a lower dose of gonadotropins. No cases of OHSS occurred and 3 patients became pregnant. PMID- 2106457 TI - Ultrasound monitoring of testis and prostate maturation in hypogonadotropic hypogonadic males during gonadotropin-releasing hormone treatment. AB - The effects of the administration of gonadotropin-releasing hormone (GnRH) on the increase of testis and prostate volume was monitored by ultrasound in six patients affected by idiopathic hypogonadotropic hypogonadism. A significant increase of testis volume was observed after 90 and 180 days (6.65 versus 3.32 mL, 99.1% net increase and 8.47 mL, 176.8% increase, respectively) of pulsatile GnRH treatment. A similar increase of prostate volume was observed at day 90 (12.67 versus 7.78 mL, 70.3% net increase) and day 180 (14.70 mL, 97.7% increase). The ultrasound monitoring of the modifications of testis and prostate volume may represent a biological assay of the effects of GnRH treatment and offer additional data on the response of target organs to the hormonal treatment. PMID- 2106459 TI - Dissecting cellulitis of the scalp in 2 girls. AB - Two girls with dissecting cellulitis of the scalp are described. In one Pseudomonas aeruginosa was isolated from the sinus discharge. Both patients were controlled with prolonged antibiotic therapy and periodic aspiration of the fluctuant lesions. Role of infection in perpetuating the condition is highlighted. PMID- 2106458 TI - Studies on a toxic metabolite from the mould Wallemia. AB - While monitoring the occurrence of toxigenic moulds in foods, using a bioassay screen, it was shown that an isolate of Wallemia sebi produced toxic effects in several of the bioassays. The toxic metabolite was isolated and purified using solvent extraction, TLC and HPLC coupled with the brine shrimp assay to monitor the toxic fractions. The purified toxin, which we propose to call walleminol A, has been partially characterized by mass spectroscopy, nuclear magnetic resonance, ultraviolet and infrared spectroscopy. It can be provisionally interpreted as a tricyclic dihydroxy compound, C15H24O2, with structural features characteristic of a sesquiterpene with an isolated double bond, but further work is required to characterize this compound unequivocally. The minimum inhibitory dose of walleminol A in the bioassays is approximately 50 micrograms/ml, which is comparable with a number of mycotoxins such as citrinin and penicillic acid. PMID- 2106460 TI - Sensillum development in the absence of cell division: the sensillum phenotype of the Drosophila mutant string. AB - We have investigated sensillum development in Drosophila embryos homozygous for mutations in the locus string (stg). In these embryos, cell division is blocked following blastoderm formation. This permits a study of the differentiative fate of undivided precursor cells, in particular those giving rise to the larval sensory organs (sensilla). Of the different cell fates normally represented in the sensilla (i.e., sensory neuron, thecogen cell, trichogen cell, tormogen cell, glia cell), only the phenotype of sensory neurons is expressed morphologically in stg embryos, suggesting that the neuronal fate predominates over the fates of the nonneuronal accessory cells. Consistent with this finding, the P element-lacZ insertion A1-2nd-29, which is a marker for trichogen and tormogen cells in the wild-type embryo, is not expressed in the body wall of the stg embryo. Some sensillum precursor cells appear to express a mixed fate in stg mutants: They express antigens (recognized by the monoclonal antibodies 22C10 and 21A6) which in the wild-type appear in separate cells (sensory neurons and thecogen cell, respectively). The differentiation of undivided cells in stg embryos is not restricted to the peripheral nervous system; in all types of tissues analyzed in this study (e.g., epidermis, intestine, muscle, CNS), precursor cells express characteristics normally exhibited by their progeny. PMID- 2106461 TI - Ultraviolet light immunomodulation of canine islets for prolongation of allograft survival. AB - Ultraviolet (UV) light treatment of donor islets has been shown to be effective for the prolongation of islet allograft survival in rodent models. This study evaluated UV as an immunomodulator of canine islets. The effects of UV irradiation on islet secretory function in vitro revealed a trend of increasing basal insulin release with increasing doses of UV and a corresponding significant decrease in glucose-mediated insulin release (expressed as percentage of basal fractional insulin release) beginning at UV light exposures of 200-300 J/m2 (n = 3, P less than 0.05). Proliferative responses to UV-irradiated allogeneic peripheral blood leukocytes and islets were significantly decreased by 53-112% (P less than 0.05) in 27 of 29 mixed-lymphocyte cultures and by 35-74% (P less than 0.05) in 4 of 5 mixed-lymphocyte islet culture experiments, respectively, beginning at 200-600 J/m2. Autotransplantation of nonirradiated (n = 8) and irradiated islets (600 J/m2, n = 6) resulted in a 1-mo graft survival rate of 75% for the control group and 50% for the irradiated group. Allotransplantation of irradiated islets (600 J/m2) into either nonimmunosuppressed recipients (1 donor to 1 recipient, n = 8) or recipients of subimmunosuppressive doses of cyclosporin (2 donors to 1 recipient, n = 4) resulted in 100% rejection by day 10. In contrast, when islets were cultured for 24 h postirradiation and transplanted into cyclosporin-treated pancreatectomized recipients (2 donors to 1 recipient), 3 of 7 grafts were prolonged beyond day 10 to days 16, 26, and greater than 100.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106462 TI - Effects of islet isografts on hemodynamic and vascular filtration changes in diabetic rats. AB - To assess the reversibility of diabetes-induced increases in regional vascular albumin permeation and blood flow and changes in kidney filtration function, islet isografts were given via the portal vein after 2 mo of streptozocin-induced diabetes in male Lewis rats. One month later, vascular function was assessed in control rats, islet-transplanted diabetic rats, and untreated diabetic rats (6-9 rats/group). Untreated diabetic rats were markedly hyperglycemic, hyperphagic, and polyuric. Transplanted rats were euglycemic within 6 days; 24-h urine volumes were virtually normalized by 2 wk and food consumption was normalized 4 wk after transplantation. Vascular albumin permeation in diabetic rats was significantly increased 1.4- to 1.7-fold in anterior uvea, choroid, retina, sciatic nerve, new granulation tissue, and kidney and was increased 1.1- to 1.3-fold in diaphragm, cecum, and optic nerve. Albumin permeation was not increased in aorta, brain, heart, or forelimb skeletal muscle. Islet transplants significantly reduced but did not completely normalize vascular albumin permeation in most tissues in which it was increased by diabetes but had no effect on albumin permeation in optic nerve, sciatic nerve, and diaphragm. Urinary excretion of endogenous albumin and IgG in diabetic rats was significantly increased 19- and 14-fold, respectively, and was virtually normalized 4 days after islet transplantation. Marked (1.8 fold) increases in glomerular filtration rate (GFR) in diabetic rats were also substantially reduced by islet transplants but remained elevated 1.4-fold control values. Likewise, diabetes-induced increases in regional blood flow were reduced in general but not normalized by islet transplants. These observations indicate that 1) diabetes-induced hemodynamic changes and alterations in vascular filtration function are not rapidly reversed by euglycemia after islet transplantation, 2) diabetes-induced increases in urinary albumin and IgG excretion are more readily normalized by euglycemia than increases in GFR and renal 125I-labeled bovine serum albumin (125I-BSA) filtration, and 3) significant increases in GFR and renal 125I-BSA filtration may not be manifested by albuminuria. PMID- 2106463 TI - A monolayer culture of gastric mucous cells from adult rabbits. AB - A new method for the primary monolayer cultures of adult rabbit gastric mucous cells has been developed. Rabbit gastric mucosal cells were isolated with etylenediaminetetraacetic acid and collagenase. Cells were cultured in Coon's modified Ham's F-12 medium supplemented with 10% fetal bovine serum, 15mM HEPES buffer, antibiotics, and antimycotic. The cells reached confluency on days 3-4. Histochemically 92% of the cells contained PAS positive gramules (mucous cells), 3% of cells showed a strong reaction for succinic dehydrogenase activity (parietal cells), 2% of the cells showed positive granules by Bowie staining (chief cells), and G6PDH staining was positive in 5% of the cells (surface mucous cells). Fibroblasts were rarely seen until day 7 (less than 1%). Thus rabbit cultured gastric cells were considered to be mainly comosed of mucous neck cells. These cells produced prostaglandin (PG) E2 and PGI2. Quantitatively cultured cells synthesized 1.475 +/- 0.039 ng/mg protein/hour of PGE2 and 0.244 +/- 0.042 pg/mg protein/hour of PGI2. This relatively simple and convenient technique provides a useful model for the study of cellular functions of gastric mucosa. PMID- 2106464 TI - Intraluminal esophageal diverticulum. AB - An intraluminal esophageal diverticulum (IED) is an uncommon entity defined as a double-layered mucosal pouch lying within the lumen of the esophagus. Its characteristic radiological finding is an intraluminal barium collection surrounded by a radiolucent halo. True IED, which is different from a transient radiological artifact, has not been previously reported in the international literature. This article describes the first case of true IED. Differential diagnosis between a true lesion and a transient flow artifact on barium meal is discussed. PMID- 2106465 TI - Anti-hepatitis C virus antibody prevails in fulminant hepatic failure. AB - Serial serum samples obtained from 27 patients with fulminant hepatic failure (FHF) in a variety of etiology were tested for anti-hepatitis C virus antibody (anti-HCV). Seven out of 10 patients (70%) with FHF due to hepatitis B virus (HBV) infection were positive for anti-HCV, showing a significantly higher rate than that in acute HBV hepatitis (0/17, 0%): In particular, all 3 post transfusion HBV-FHF cases were found to be positive for the antibody. The incidence of anti-HCV in sporadic non-A non-B (NANB)-FHF patients (7/11, 64%) tended to be greater than that in acute sporadic NANB hepatitis as recently surveyed in this country. In addition, anti-HCV was also detected in a patient with hepatitis A virus (HAV)-FHF and in 2 out of 4 drug-induced FHF patients. Moreover, anti-HCV appeared earlier in FHF (median; 27.5 days, n = 9) regardless of etiology, when compared to acute NANB hepatitis (3 to 6 months). Hence, co infection and/or superinfection of HCV with enhanced antibody response may play an important role in the development of this fatal disease. PMID- 2106466 TI - A diagnostic approach to different types of non-A non-B acute hepatitis through the evaluation of the lobular distribution of hepatocytic damage. AB - The activity in the serum of three hepatic mitochondrial enzymes, glutamate dehydrogenase (GDH), ornithine carbamyl transferase (OCT) and mitochondrial glutamic oxaloacetic transaminase (m-GOT), all of which show different lobular distribution in the liver, was investigated in order to clarify the usefulness of determinations of these enzymes for the diagnosis of different types of acute non A non-B (NANB) hepatitis. In NANB hepatitis, there were two different histological types: portal and non-portal. In most portal cases, the GDH/OCT ratios were lower than 0.35, but the ratios were higher than 0.36 in all non portal cases. The prognosis of the portal group and the short incubation group of NANB hepatitis was better than that of the non-portal and the long incubation group, respectively. The cases showing GDH/OCT ratios of less than 0.35 clearly displayed better prognoses than the cases showing high GDH/OCT ratios. These findings implied that the low GDH/OCT group may have been infected by particular viruses and that ratio determination is useful for the diagnosis of NANB hepatitis caused by different viruses. PMID- 2106467 TI - Histological improvement of chronic hepatitis B, and non-A, non-B with interferon treatment: application of a numerical scoring system for evaluating sequential morphologic changes. AB - In order to assess the sequential changes of liver pathology after interferon therapy, 70 liver biopsy specimens, collected from 23 HBeAg-positive patients with chronic hepatitis B and 12 patients with chronic non-A, non-B hepatitis, were studied using a numerical scoring system proposed by Knodell et al. The biopsy specimens were obtained immediately prior to the administration of interferon and within one week following the termination of interferon therapy. Three patients with chronic hepatitis B were negative for DNA-polymerase (DNA-P) prior to the interferon administration. Ten patients (50%) lost DNA-P activity. HBeAg became negative in 8 patients (34.8%), of whom 2 seroconverted to anti-HBe. Serum alanine aminotransferase levels normalized in 9 patients with chronic hepatitis B, and non-A, non-B hepatitis. The total Histological Activity Index (HAI) scores in both patients with chronic hepatitis B, and non-A, non-B decreased significantly (P less than 0.001 and P less than 0.005, respectively) after interferon treatment. There was also a significant improvement (0.02 less than P less than 0.001) in each histological category except for fibrosis. When the changes of the HAI scores in patients with chronic hepatitis B were correlated to the outcome in the DNA-P and HBeAg/anti-HBe system after treatment, the histological improvement did not significantly correlate to the outcome of these serological parameters. PMID- 2106468 TI - Arachidonic acid stimulates steroidogenesis in goldfish preovulatory ovarian follicles. AB - The possibility that arachidonic acid (AA) plays a role in the regulation of steroidogenesis in goldfish was investigated using preovulatory ovarian follicles incubated in vitro. AA was shown to act in a time- and dose-dependent manner to stimulate testosterone production. AA in the range of 10(-5) to 10(-4) M increased testosterone production within 2 hr and had a maximal effect by 9 hr. The magnitude of the testosterone response to AA was similar to that observed when ovarian follicles were incubated with human chorionic gonadotropin (hCG). Ovarian follicles incubated with AA and either hCG or forskolin (adenylate cyclase activator) produced more testosterone than follicles incubated with either of these compounds alone. The actions of AA on testosterone production were completely blocked by cyclooxygenase inhibitors (indomethacin or ibuprofen) and were reduced by 50% by the lipoxygenase inhibitor nordihydroguaiaretic acid. Phospholipase C was far more effective than phospholipase A2 in the stimulation of testosterone production. Taken together, these results suggest that AA formed subsequent to the action of phospholipase C on membrane phospholipids has a role in the regulation of steroidogenesis in preovulatory goldfish ovarian follicles. PMID- 2106469 TI - Use of a pituitary cell dispersion method and primary culture system for the studies of gonadotropin-releasing hormone action in the goldfish, Carassius auratus. II. Extracellular calcium dependence and dopaminergic inhibition of gonadotropin responses. AB - Primary static cultures of dispersed goldfish pituitary cells obtained by controlled trypsinization released gonadotropin (GTH) in response to 2-hr stimulations of 0.1 nM to 1 microM [Trp7,Leu8]-gonadotropin-releasing hormone (sGnRH), [D-Arg6,Pro9-N-ethylamide]-sGnRH (sGnRHa), and [His5,Trp7,Tyr8]-GnRH (cGnRH-II) in a dose-dependent manner. Coincubation with 10 to 1000 nM of a dopamine agonist, apomorphine, dose dependently reduced the GTH response to increasing concentrations of sGnRH. Apomorphine at 1 microM completely abolished the dose-dependent GTH response to sGnRHa and cGnRH-II, but only partially inhibited the GTH-releasing action of high concentrations of sGnRH. Addition of calcium ionophores, 1 to 100 microM A23187 and 10 to 100 microM ionomycin, significantly increased GTH release. The ED50S of the GTH response to A23187 and ionomycin were 0.88 +/- 0.15 and 13.67 +/- 2.76 microM, respectively. Incubation with Ca2(+)-deficient media (media prepared without the addition of Ca2+ salts) did not significantly affect basal GTH release, but severely decreased the hormone response to increasing concentrations of sGnRH, A23187, and ionomycin. These results confirm the direct inhibitory dopaminergic influence on GTH release in goldfish and further suggest that extracellular Ca2+ plays a role in mediating GnRH action on gonadotropes in fish. PMID- 2106470 TI - smellblind: a gene required for Drosophila olfaction. AB - In this article we define and characterize the smellblind gene (sbl). We show that two mutants, sbl and olfDx9, both isolated by virtue of their olfactory phenotypes and analyzed extensively by others with respect to courtship behavior, contain mutations at a single locus. Meiotic recombination, duplication, and deficiency mapping are used to localize this gene, sbl, to cytogenetic position 14F6-15A2-3 on the X chromosome. Mutations of the locus are shown to produce severe defects not only in larval olfactory response to several volatile chemicals, but also in larval contact chemosensory response. Both sbl and olfDx9 give a robust response, however, in a new test of larval phototactic response, which we describe here. Both alleles are shown to be heat-sensitive lethals. Four additional recessive lethal alleles, two EMS-induced, one dysgenic, and one spontaneous, are also described. PMID- 2106471 TI - A DNA-binding protein containing two widely separated zinc finger motifs that recognize the same DNA sequence. AB - We have isolated a full-length cDNA clone encoding a protein (PRDII-BF1) that binds specifically to a positive regulatory domain (PRDII) of the human IFN-beta gene promoter, and to a similar sequence present in a number of other promoters and enhancers. The sequence of this protein reveals two novel structural features. First, it is the largest sequence-specific DNA-binding protein reported to date (298 kD). Second, it contains two widely separated sets of C2-H2-type zinc fingers. Remarkably, each set of zinc fingers binds to the same DNA sequence motif with similar affinities and methylation interference patterns. Thus, this protein may act by binding simultaneously to reiterated copies of the same recognition sequence. Although the function of PRDII-BF1 is not known, the level of its mRNA is inducible by serum and virus, albeit with different kinetics. PMID- 2106472 TI - The potentiating effect of the simultaneous administration of tolbutamide, glibenclamide, and gliclazide on the development of alloxan-induced diabetes in rats. PMID- 2106473 TI - Chronic stimulation of basal prolactin (PRL) secretion by growth hormone releasing hormone (GHRH) in children with GH neurosecretory dysfunction. PMID- 2106474 TI - Therapy of chronic hepatitis B with recombinant human alpha and gamma interferon. AB - Eight patients with chronic hepatitis B entered a pilot study of gamma interferon and alpha interferon in combination. Gamma interferon alone had minimal inhibitory effects on serum levels of hepatitis B virus as monitored by serum HBV DNA and DNA-polymerase activity. The drug also gave troublesome side effects. In contrast, alpha interferon had more potent inhibitory effects on serum HBV levels and fewer side effects. When combined, the two interferons showed no additive or synergistic effects in inhibiting serum levels of HBV DNA or DNA polymerase. These findings indicate that the addition of gamma interferon to alpha interferon provides no additional antiviral effects but contributes significantly to side effects. PMID- 2106475 TI - Hepatitis C virus: a giant leap forward. PMID- 2106476 TI - The presence of anti-HCV antibodies in the serum of patients with chronic active hepatitis and antinuclear antibodies. PMID- 2106477 TI - Chronic care: a future delivery model? AB - If demographic predictions are right, the chronic care patient population will have a significant effect on future health care delivery systems. As baby-boomers age and become debilitated with chronic disease and conditions, and as premature babies and young trauma and chronic disease victims survive with increased disability, acute care hospital administrators will have to focus more attention on these patients. But what is this patient population like? One of the steps to understanding the chronic care market is to form a realistic profile of these patients, say executives. They are not all elderly, and they are not all near death. But they are savvy consumers who demand high-quality, patient-centered care. PMID- 2106478 TI - Genetic studies on human thyroxine-binding globulin (TBG). AB - An enzyme immunoassay technique combined with Western blotting is described to demonstrate thyroxine-binding globulin (TBG) by isoelectric focusing in thin layer polyacrylamide gels with 8 mol/l urea. Quantitative evaluation was by laser densitometry. No genetic charge variants of TBG were encountered in a sample of 840 unrelated individuals from southwestern Germany. There was no correlation between structural and quantitative variations in the TBG protein. Results from a family with quantitative TBG deficiency strongly support the postulated X-linked mode of inheritance. The method described can be considered as an additional diagnostic tool in thyroid evaluation. PMID- 2106479 TI - Molecular cloning of DNA from specific chromosomal regions by microdissection and sequence-independent amplification of DNA. AB - A method that permits the in vitro amplification and cloning of DNA dissected from specific regions of a chromosome and does not require prior knowledge of the DNA sequence is described. DNA from several different chromosomal loci in the Drosophila melanogaster genome has been isolated by this method. Although the procedure was developed to permit the isolation of DNA sequences from serial sections of a single microdissected polytene chromosome, it should be useful for obtaining DNA clones from specific regions of the nonpolytene chromosomes of other organisms as well. PMID- 2106480 TI - Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene. AB - Point mutations in the factor VIII gene are responsible for the majority of cases of hemophilia A, and only a small fraction of these mutations can be recognized by restriction endonuclease analysis. We have now used polymerase chain reaction and denaturing gradient gel electrophoresis to characterize single nucleotide substitutions in the factor VIII gene. Five regions of the gene were studied: exon 8, the 3' end of exon 14, exon 17, exon 18, and exon 24. A GC clamp was attached to the 5' PCR primer to allow detection of the majority of single base changes in DNA fragments ranging from 249 to 356 bp. Ten of eleven known point mutations were definitively separated. Fifty-two patients with unknown mutations were then studied by these methods, and the disease-producing mutation was found in three. First, we identified a new missense mutation in exon 14 which is the likely cause of hemophilia A in one patient (tyrosine changed to cysteine at amino acid residue 1709). Second, we found a new missense mutation in exon 18 in one patient (asparagine to aspartic acid at amino acid residue 1922). Third, a previously described mutation in exon 24 was detected (arginine changed to glutamine at amino acid residue 2209). In addition, a new polymorphic nucleotide substitution was found in intron 7. Moreover, these mutations can be detected when the GC-clamped PCR products from all five regions are run in the same denaturing gel. Our results indicate that denaturing gradient gel electrophoresis can be successfully applied to the analysis of point mutations in large genes whose transcripts are not readily available. PMID- 2106481 TI - cDNA isolation, expression analysis, and chromosomal localization of two human zinc finger genes. AB - On the basis of sequence similarity in the repeated zinc finger domain, we have identified and characterized two human cDNA clones (ZNF7 and ZNF8), both encoding proteins containing potential finger-like nucleic acid binding motifs. Northern blot analysis indicates that both genes are expressed as multiple transcripts and they are ubiquitously present in many human cell lines of different embryological derivation. Moreover, their expression is modulated during in vitro induced terminal differentiation of human myeloid cell line HL-60. By in situ hybridization experiments, we have localized the ZNF7 gene to chromosome 8 (region q24) and the ZNF8 gene to the terminal band of the long arm of chromosome 20 (20q13). PMID- 2106482 TI - Immune responses in BALB/c mice following immunization with aromatic compound or purine-dependent Salmonella typhimurium strains. AB - Two near isogenic strains of Salmonella typhimurium HWSH, stably mutated in either the aroA gene affecting the biosynthesis of aromatic compounds, or the purA gene affecting the biosynthesis of purines, were administered intravenously as live attenuated vaccines to BALB/c mice. HWSH aroA-immunized mice were well protected against intravenous (i.v.) challenge with wild-type virulent HWSH for at least 10 weeks, whereas HWSH purA-immunized mice were unprotected. Furthermore, HWSH aroA-immunized mice could also control a heterologous challenge with virulent Listeria monocytogenes at 7 and 14 days post-immunization, whereas mice receiving a similar dose of HWSH purA could not. Increasing the i.v. dose of HWSH purA compared to HWSH aroA induced some resistance to L. monocytogenes. Induction of early anti-S. typhimurium resistance by HWSH aroA immunization appeared slightly later than the anti-L. monocytogenes resistance. Mice immunized with either vaccine were able to mount S. typhimurium-specific T-cell proliferative responses and produced anti-S. typhimurium humoral antibodies in their serum. The antibody titre was greater in those mice immunized with the aroA mutant. PMID- 2106483 TI - The role of antibody affinity and titre in immunity to Schistosoma mansoni following vaccination with highly irradiated cercariae. AB - Sera from rabbits and rats vaccinated with highly irradiated cercariae of Schistosoma mansoni (VRabS, VRatS) were found to be of substantially higher affinity than sera from CBA mice vaccinated four times (4 X CVMS), single sex sera (SSS) or chronic infection sera (CIS). In contrast, VRabS and SSS appeared to possess the highest titres of antibody, followed by CIS and VRatS, with 4 X CVMS displaying the lowest titre. Two mouse strains selectively bred for high affinity (HA) or low-affinity (LA) antibody following vaccination were tested for their ability to resist a challenge infection. LA mice, which produce high titres of low-affinity antibody, manifested significantly more resistance than HA mice, which produce low titres of high-affinity antibody. Immunoprecipitation studies demonstrated that sera from vaccinated LA mice (LVMS) recognized 125I-labelled schistosomular surface antigens more intensely than sera from vaccinated HA mice (HVMS). However, peritoneal macrophages from HA and LA mice in the presence of HVMS, LVMS or 4 X CVMS, and naive macrophages activated in vitro with interferon gamma (IFN-gamma)/lipopolysaccharide (LPS) mediated comparable levels of schistosomula killing in vitro. The experiments described here provide evidence that the titre of antibody rather than its affinity may be a more critical factor in the development of optimal immunity to S. mansoni. PMID- 2106484 TI - MHC class II antigen expression in human vascular smooth muscle cells is induced by interferon-gamma and modulated by tumour necrosis factor and lymphotoxin. AB - Arterial smooth muscle cells (SMC) express major histocompatibility complex (MHC) class II antigens in experimental vasculitis and in the human atherosclerotic plaque. We have therefore studied the regulation of expression of MHC antigens in cultured human arterial SMC, using immunofluorescence, radioimmunoprecipitation and a quantitative cell-surface immunoradiometric assay. SMC expressed class I, but not class II, antigens on their cell surfaces under basal conditions. Treatment of SMC with recombinant or natural interferon-gamma (IFN-gamma) induced expression of class II antigens in the following order of intensity, DR greater than DP greater than DQ. HLA-DR protein in SMC showed the same MW as that synthesized by B-lymphoblastoid cells. Antibodies to IFN-gamma blocked all HLA-DR inducing activity in mixed leucocyte reaction (MLR) supernatants and PHA stimulated peripheral blood mononuclear cell (PBMC)-conditioned media, indicating that IFN-gamma is the only lymphokine secreted under these conditions that is capable of de novo induction of HLA-DR expression in SMC. Treatment of SMC with recombinant human tumour necrosis factor-alpha (TNF) or lymphotoxin (LT) did not per se induce class II antigen expression. However, both TNF and LT substantially enhanced IFN-gamma-induced expression of HLA-DQ while decreasing that of HLA-DP. TNF, but not LT, increased HLA-DR expression. Also, in dermal fibroblasts, IFN gamma-induced HLA-DP expression was significantly inhibited in the presence of TNF. These data demonstrate that TNF and LT differentially modulate IFN-gamma induced MHC antigen expression in mesenchymal cells. The fact that SMC can express MHC class II antigens suggests that this cell type may serve as an accessory cell in the initiation of the immune response. PMID- 2106485 TI - T cells and neutrophils exhibit differential adhesion to cytokine-stimulated endothelial cells. AB - In vitro adhesion assays were used to directly compare the adhesion of polymorphonuclear leucocytes (PMN) and T cells to endothelial cells (EC). PMN exhibited lower binding to unstimulated EC than T cells. When EC were stimulated with interleukin-1 (IL-1), tumour necrosis factor (TNF) or bacterial lipopolysaccharide (LPS) there was a large and rapid increase in adhesiveness for PMN which peaked at 4 hr. This had fallen significantly by 24 hr and by 72 hr was not significantly elevated above unstimulated adhesion. The increase in adhesiveness of cytokine-stimulated EC for T cells was smaller and more gradual than for PMN, with adhesion peaking around 8 hr and remaining significantly elevated at 72 hr. In contrast, interferon-gamma (IFN-gamma) enhanced EC adhesiveness for T cells but not for PMN, with maximal T cell EC adhesiveness occurring 24 hr after stimulation. As leucocyte adhesion to vascular endothelium is the first step in diapedesis, differences in PMN and T-cell adhesion to EC may be important in determining the timing and composition of inflammatory infiltrates. PMID- 2106486 TI - Production of tumour necrosis factor by mastocytoma P815 cells. AB - P815, a transformed mouse mastocytoma cell line, produced and released cytotoxic factors after stimulation with phorbol 12-myristate 13-acetate (PMA), but not with lipopolysaccharide (LPS), calcium ionophore A23187 and IgE receptor triggering. The cytotoxic activity was reduced 60% by antibodies to mouse tumour necrosis factor (TNF). In addition, we demonstrated that TNF mRNA was already expressed under normal culture conditions and that it increased after stimulation with PMA. Although it was unknown whether factors other than TNF were lymphotoxin or some other unknown factors, it has been suggested that mast cells have cytotoxic activity, and that they contribute to inflammatory response through the release of TNF, which has a wide range of biological activity. PMID- 2106487 TI - Activation of the respiratory burst in murine phagocytes by certain guanine ribonucleosides modified at the 7 and 8 positions: possible involvement of a pertussis toxin-sensitive G-protein. AB - The capacity of certain guanine ribonucleosides (modified at the 7 and/or 8 positions) to enhance the respiratory burst of murine peritoneal phagocytes was evaluated. The results show that 8-mercaptoguanosine, 8-bromoguanosine, 7-methyl 8-oxoguanosine and 7-thia-8-oxoguanosine, when injected intraperitoneally into mice, induced peritoneal phagocytes to generate reactive oxygen species as early as 1 h after injection. In vivo administration of the nucleosides induced higher levels of phagocyte activation than in vitro treatment with the same nucleosides. However, the addition of interferon alpha/beta in vitro significantly increased the magnitude of phagocyte activation by the nucleosides, suggesting an important role for cytokines/lymphokines in the nucleoside-induced phagocyte activation in vivo. Furthermore, pre-treatment of phagocytes in vitro with Bordetella pertussis toxin, before treatment with the guanosines, inhibited their capacity to induce the respiratory burst. These observations establish these low-molecular-weight compounds as interesting probes for the study of stimulus-response coupling in phagocytes. PMID- 2106488 TI - In vitro inhibition of IL-2 biosynthesis in activated human peripheral blood mononuclear cells by a trauma-induced glycopeptide. AB - Traumatic injury often results in profound immunopathology that can lead to immunosuppression, thereby increasing the morbidity and mortality due to sepsis. The isolation and partial characterization of an immunosuppressive glycopeptide (SAP) from serum of severely burned patients has previously been reported by our laboratory. Recently, this trauma peptide has also been identified in the serum of patients with multiple blunt trauma. This glycopeptide is capable of suppressing neutrophil chemotaxis, T-cell blastogenesis and the lysis of human erythrocytes. We demonstrate in this report that SAP inhibits interleukin 2 (IL 2) biosynthesis by mitogen-stimulated peripheral blood mononuclear cells. Peptide concentrations of 50 nmol and above significantly inhibited IL-2 production. Inhibition was not reduced by the addition of indomethacin or anti-PGE2 to cultures containing greater than 100 nmol of peptide, suggesting that inhibition is not entirely prostaglandin-mediated. Preliminary studies have shown that IL-2 suppression by SAP can be partially reversed by the addition of calcium ionophore. These results suggest a potential immunosuppressive mechanism of the trauma peptide in which T cell blastogenesis is inhibited by interference in IL-2 biosynthesis. PMID- 2106489 TI - Relative permissiveness of macrophages from black and white people for virulent tubercle bacilli. AB - Epidemiological, clinical, and histopathological evidence suggests that black people are more susceptible to tuberculosis than are white people. The cellular basis of this putative susceptibility was investigated in vitro by comparing responses of blood-derived macrophages from black and white donors to experimental infection with virulent tubercle bacilli. Phagocytes from pairs of black and white donors were infected. The uptake and replication of the tubercle bacilli in these cells were measured by microscopic counts and by CFU counts of bacilli at 0, 4, and 7 days. The effects of donor serum, of 1,25-(OH)2-vitamin D3, and gamma interferon on the infection also were studied. Black-donor phagocytes killed more bacilli during phagocytosis than white-donor phagocytes did. However, the bacilli grew consistently and significantly faster in successfully infected macrophages from black than from white donors, especially in the presence of black-donor serum. 1,25-(OH)2-vitamin D3 gave significantly less protection against tubercle bacilli to macrophages from black donors than to macrophages from white donors. The permissiveness of the macrophages from the two races was affected equally by gamma interferon. These results demonstrate some inherent and environmental liabilities in the monocytic phagocytes and serum of black people compared with white people, which may contribute to their greater susceptibility to tuberculosis. PMID- 2106490 TI - A recombinant Rickettsia conorii vaccine protects guinea pigs from experimental boutonneuse fever and Rocky Mountain spotted fever. AB - There are no vaccines against boutonneuse fever and Rocky Mountain spotted fever. Previous studies have identified a Rickettsia rickettsii surface protein as a vaccine candidate and shown that an antigenically related protein is present in R. conorii, which causes boutonneuse fever. The gene encoding the R. rickettsii protein has been cloned and expressed in Escherichia coli. We confirmed by 7.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis of rickettsial lysates followed by immunoblotting with a monoclonal antibody raised against the R. rickettsii protein that an analogous protein exists in R. conorii. Although these proteins were previously called 155-kilodalton (kDa) proteins, we found that their apparent molecular masses were 198 kDa for R. conorii Kenya tick typhus and 190 kDa for R. rickettsii R. Using the R. rickettsii gene probe, we cloned and expressed a 5.5-kilobase HindIII fragment from R. conorii Kenya tick typhus genomic DNA in E. coli JM107. The expressed recombinant product was recognized by a monospecific polyclonal rabbit antiserum prepared against the 198-kDa protein. Guinea pigs immunized with sonic lysates of the E. coli strain expressing the recombinant gene product developed antibodies recognizing R. conorii when tested by a microimmunofluorescence antibody assay. Upon immunoblotting of rickettsial lysates, those antisera specifically recognized the 198-kDa R. conorii protein and its 190-kDa analog in R. rickettsii. Guinea pigs immunized with sonic lysates of the recombinant E. coli expressing the 198-kDa protein were protected from experimental infections with the homologous R. conorii strain and partially protected from experimental infections with a strain of the heterologous species R. rickettsii. These findings show that the 198-kDa R. conorii protein is a candidate for a vaccine against boutonneuse fever. PMID- 2106491 TI - Expression of systemic protection and delayed-type hypersensitivity to Listeria monocytogenes is mediated by different T-cell subsets. AB - The relationship between acquired cellular resistance and delayed-type hypersensitivity (DTH) during the immune response to Listeria monocytogenes was investigated. Treatment of concanavalin A-stimulated Listeria-immune spleen cells with anti-CD8 antibody plus complement abrogated the adoptive transfer of systemic antilisterial immunity but had no effect on the transfer of DTH. In contrast, in vitro depletion of the CD4+ T-cell subset eliminated the ability of culture-activated cells to transfer DTH reactivity but did not interfere with the adoptive transfer of protection. In vivo, the infusion of anti-CD8 antibody inhibited the expression of both actively and adoptively transferred protection but did not influence the development of DTH skin test reactivity to L. monocytogenes antigens. In vivo depletion of the CD4+ T-cell subset eradicated the DTH response, with only minor influence of the protective anti-Listeria response. The apparent functional dissociation of the CD4+ (DTH) and CD8+ (protection) T-cell populations was further emphasized by our findings that the adoptive transfer of protection was dependent on a cyclophosphamide-sensitive cell population, whereas DTH reactivity was mediated by a cyclophosphamide resistant population. PMID- 2106492 TI - Characterization of phospholipase C from Pseudomonas aeruginosa as a potent inflammatory agent. AB - Phospholipase C (PLC) from Pseudomonas aeruginosa induced a marked inflammatory response when injected intraperitoneally in C3H/HeJ mice. This inflammation was characterized by the accumulation of inflammatory cells and plasma protein and the release of arachidonic acid metabolites (6-trans-12-epi-leukotriene B4 [LTB4], 6-trans-LTB4, LTB4, 5-HETE (5-hydroxyeicosatetraenoic acid), LTC4, LTD4, LTE4, prostaglandin E2 [PGE2], PGF2-alpha, and thromboxane B2 [TxB2]) in the peritoneal cavity of the mice. Heat-inactivated PLC did not evoke any of these effects, suggesting that enzyme activity is necessary for PLC-induced inflammation. When human granulocytes were incubated with PLC in vitro, 6-trans 12-epi-LTB4, 6-trans-LTB4, LTB4, 5-HETE, and PGE2 were generated. Mouse peritoneal cells stimulated with PLC released 6-trans-LTB4, LTB4, PGE2, PGF2 alpha, and TxB2. Both human granulocytes and mouse peritoneal cells stimulated with PLC generated significantly increased levels of arachidonic acid metabolites as compared with cells incubated with heat-inactivated PLC. Leukotriene production by both populations of cells was inhibited when the cells were preincubated with nordihydroguaiaretic acid and subsequently stimulated with PLC. Similarly, both cell types released significantly lower amounts of cyclooxygenase pathway products when they were preincubated with indomethacin and subsequently stimulated with PLC. PMID- 2106493 TI - Synthesis of a select group of proteins by Neisseria gonorrhoeae in response to thermal stress. AB - We report the thermal conditions that induce the heat shock response in Neisseria gonorrhoeae. Under conditions of thermal stress, Neisseria gonorrhoeae synthesizes heat shock proteins (hsps), which differ quantitatively from conventionally studied gonococcal proteins. Gonococci accelerate the rate of synthesis of the hsps as early as 5 min after the appropriate stimulus is applied, with synthesis continuing for 30 min, as demonstrated by in vivo labeling experiments with L-[35S]methionine. Two of the gonococcal hsps are immunologically cross-reactive with the hsps of Escherichia coli, DnaK and GroEL, as demonstrated by Western blot (immunoblot) analysis. Ten hsps can be identified on two-dimensional autoradiograms of whole gonococci (total protein). Four hsps can be identified on two-dimensional autoradiograms of 1% N-lauroylsarcosine (sodium salt) (Sarkosyl)-insoluble membrane fractions. Two of the hsps from the 1% Sarkosyl-insoluble fraction are found exclusively in this fraction, suggesting that they are membrane proteins. The identification of this group of proteins will facilitate further study of the function of these proteins and provide insight into the possible role of hsps in disease pathogenesis. PMID- 2106494 TI - Phosphorylase-cross-reactive antibodies evoked by streptococcal M protein. AB - Rabbit antisera evoked by type 5 streptococcal M protein (M5) were screened by enzyme-linked immunosorbent assay (ELISA) for immunological cross-reactivity with purified rabbit muscle phosphorylases a and b. Of 10 pep M5 antisera tested, 3 showed significant cross-reactivity with both forms of the enzyme. ELISA inhibition studies using one of the pep M5 antisera showed that all of the phosphorylase b antibodies were inhibited by pep M5, the immunogen, and phosphorylase b, the ELISA antigen. All of the antibodies were also inhibited by pep M6 and pep M19, but not by pep M24, indicating that the cross-reactive epitopes were shared by multiple serotypes of M protein. Western blot (immunoblot) analyses showed that pep M5 antisera reacted strongly with the subunit of phosphorylase b. In addition, purified phosphorylase partially inhibited the binding of pep M5 antibodies to a 95-kilodalton protein of human myocardium. One of the three cross-reactive pep M5 antisera inhibited the enzymatic activity of phosphorylase a in a dose-related fashion, reaching a maximum inhibition of 75%. The enzymatic activity in the presence of antibody was totally restored when the antiserum was first incubated with pep M5. PMID- 2106495 TI - Inhibitory and stimulatory effects of Pseudomonas aeruginosa pyocyanine on human T and B lymphocytes and human monocytes. AB - Pyocyanine, a pigment produced by Pseudomonas aeruginosa, has dual dose-dependent stimulatory as well as inhibitory effects on immune responses in vitro as measured by DNA synthesis of human T and B lymphocytes, interleukin-2 (IL-2) production by human T lymphocytes, immunoglobulin production by human B lymphocytes, and monokine production by human monocytes. In general, stimulatory activity was found at low concentrations of pyocyanine, whereas high concentrations of the pigment resulted in an inhibition of responses. At a pyocyanine concentration of 0.1 micrograms/ml or less the proliferation of T and B lymphocytes was enhanced, but at 0.5 micrograms/ml it was suppressed. IL-2 production by T lymphocytes was enhanced at concentrations up to 0.5 micrograms/ml but totally inhibited at 1.0 micrograms/ml. The differentiation of B lymphocytes to become immunoglobulin-producing cells was also enhanced in the presence of low doses of pyocyanine, whereas secretion of immunoglobulin by B lymphocytes was suppressed at all concentrations of pyocyanine. In contrast to the dual effects of pyocyanine on lymphocyte response, lipopolysaccharide-induced IL-1 and tumor necrosis factor release by monocytes was markedly enhanced by low as well as high concentrations of pyocyanine. From these results we conclude that this property of pyocyanine may lead to suppression of specific defense mechanisms and enhance harmful inflammatory reactions of the host during infection with Pseudomonas aeruginosa. PMID- 2106496 TI - Extramedullar proliferation of eosinophil granulocytes in chronic schistosomiasis mansoni is mediated by a factor secreted by inflammatory macrophages. AB - In chronic murine schistosomiasis mansoni, extramedullar myelopoiesis of eosinophils has been described, associated with tissue inflammatory infiltrates and periovular granulomas. It may be experimentally induced by intraperitoneal glass implants in mice with chronic schistosomiasis but not in normal mice or in mice with acute schistosomiasis. In vivo studies showed that this induction depended on macrophages adherent to the implants. In an in vitro test with bone marrow cells, we demonstrated that this eosinophil proliferation was mediated by a factor secreted by the mobilized macrophages. In contrast to murine interleukin 5 (IL-5), which induced both proliferation and differentiation of eosinophils, the studied monokine did not induce their maturation. A potent neutralizing monoclonal antibody for murine IL-5 did not abrogate the stimulatory activity of the monokine, indicating that it is a cytokine distinct from IL-5. These data, together with a quantitation of bone marrow, blood, and peripheral eosinophils, indicated that in chronic schistosomiasis, the systemic medullar supply of eosinophils is supplemented in tissues by their local proliferation, mediated by macrophages mobilized in local granulomatous and diffuse inflammatory reactions. PMID- 2106497 TI - Murine gamma interferon fails to inhibit Toxoplasma gondii growth in murine fibroblasts. AB - Although treatment of human macrophages or fibroblasts with human gamma interferon results in the inhibition of intracellular Toxoplasma gondii, murine gamma interferon stimulated only murine macrophages, not murine fibroblasts, to inhibit T. gondii. This species difference may be important in understanding the control of acute and chronic toxoplasmosis. PMID- 2106498 TI - Social network assessment: a critical component in case management for functionally impaired older persons. AB - Case managers who develop long-term care service plans for functionally impaired elderly persons must integrate the supportive efforts of the client's social network into the overall service approach. The ultimate goal is to develop a plan whereby the formal service providers supplement rather than supplant the care and assistance available from the older person's network. This article presents a framework that identifies those variables associated with the relationship dynamics that exist between older persons and their social network members. The framework can be used by case managers to help them assess the characteristics and functioning of their clients' social network relations and develop service strategies that maximize the helping efforts of those networks. PMID- 2106499 TI - Cervical-cancer screening: attendance and cost-effectiveness. AB - The influence of attendance on the health effects and cost-effectiveness of cervical-cancer screening was studied, both for organized screening programmes and for spontaneous screening. The asymmetric distribution of smears among the female population and the higher risk incurred by women who never or only occasionally attend screening appear crucial in determining the health effects of screening. An increase in attendance rate induces a substantial rise in health effects and a less than proportionate rise in costs, thus improving cost effectiveness. Wider screening coverage, in order to increase the number of life years saved, is achieved more efficiently by encouraging a greater number of women to attend than by inviting the same number of women to attend more often, i.e., with a shorter interval between successive screens. Spontaneous screening is characterized by high coverage for younger women and low coverage for middle aged and older women. This leads to a small amount of health effects and poor cost-effectiveness as compared with organized screening. PMID- 2106500 TI - Increased levels of 5-fluorouracil-induced DNA lesions in Bloom's syndrome. AB - In Bloom's syndrome (BS) the regulation of uracil-DNA glycosylase, an enzyme involved in the repair of DNA containing 5-FU, is altered. 5-FU induces higher levels of DNA fragmentation in BS cells than in non-BS cells. The increase in DNA fragmentation is connected to the cytotoxic mechanism where 5-FU is incorporated into DNA. When 5-FU induces DNA fragmentation by a mechanism not involving the incorporation of drug into DNA, the levels of DNA fragmentation in BS and non-BS cells remain similar. PMID- 2106501 TI - Mast cell tumors in three ferrets. AB - Pruritic open skin lesions (5 mm diameter) on the thorax, neck, or head of 3 ferrets were diagnosed as mast cell tumors. Diagnosis of the tumors was based on histologic examination of biopsy specimens. Histologic diagnosis was necessary because the lesions had been treated as mycotic or bacterial ulcers and did not respond to conventional treatment. Excised mast cell tumors did not recur, and malignant behavior of the tumors was not observed. PMID- 2106502 TI - Production, isolation and structure determination of a novel beta-glucosidase inhibitor, cyclophellitol, from Phellinus sp. AB - In the course of our screening of beta-glucosidase inhibitor, a culture filtrate of a mushroom, Phellinus sp. strongly inhibited the enzyme activity. The active substance was isolated through charcoal separation, column chromatography and crystallization. Spectroscopic and crystallographic analysis revealed that it had a novel cyclitol structure, (1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7 oxabicyclo[4,1,0]heptane-2,3,4-tri ol, and we named it cyclophellitol. It inhibited almond-derived beta-glucosidase with an IC50 of 0.8 micrograms/ml. PMID- 2106503 TI - Eponemycin, a new antibiotic active against B16 melanoma. I. Production, isolation, structure and biological activity. AB - Streptomyces hygroscopicus No. P247-71(ATCC 53709)produced a novel antibiotic eponemycin which exhibited specific in vivo antitumor effect against B16 melanoma. Structural studies assigned (4S)-1,2-epoxy-2-hydroxymethyl-4-(N isooctanoyl-L- serylamino)-6-methylhept-6-ene-3-one to eponemycin which is unrelated to the known antitumor antibiotics. PMID- 2106504 TI - Microbial growth patterns described by fractal geometry. AB - Fractal geometry has made important contributions to understanding the growth of inorganic systems in such processes as aggregation, cluster formation, and dendritic growth. In biology, fractal geometry was previously applied to describe, for instance, the branching system in the lung airways and the backbone structure of proteins as well as their surface irregularity. This investigation applies the fractal concept to the growth patterns of two microbial species, Streptomyces griseus and Ashbya gossypii. It is a first example showing fractal aggregates in biological systems, with a cell as the smallest aggregating unit and the colony as an aggregate. We find that the global structure of sufficiently branched mycelia can be described by a fractal dimension, D, which increases during growth up to 1.5. D is therefore a new growth parameter. Two different box counting methods (one applied to the whole mass of the mycelium and the other applied to the surface of the system) enable us to evaluate fractal dimensions for the aggregates in this analysis in the region of D = 1.3 to 2. Comparison of both box-counting methods shows that the mycelial structure changes during growth from a mass fractal to a surface fractal. PMID- 2106505 TI - Carbon monoxide dehydrogenase inhibitor in cell extracts of Pseudomonas carboxydovorans. AB - Extracts of heterotrophically grown cells of Pseudomonas carboxydovorans were found to contain an inhibitor of carbon monoxide dehydrogenase (CO-DH). The inhibitor activity was not detected in CO-autotrophically grown cells. The inhibitor was extremely stable to heat treatment based on the extent of inhibition of CO-DH activity. The extent of inhibition was proportional to the amount of cell extract added to the reaction mixture. The inhibition was independent of a prior incubation period of the extracts with CO-DH. The inhibitor was precipitable with ammonium sulfate, phenol, and trichloroacetic acid. It was passed through benzoylated dialysis tubing and Amicon ultrafiltration membrane YM2. Denaturing and nondenturing polyacrylamide gel electrophoresis of CO-DH inactivated by inhibitor revealed that the mobilities of native enzyme and subunits were identical to those of active CO-DH. The inhibitor treated CO-DH retained its original antigenic sites and exhibited enzyme activity upon activity staining. The CO-DH inhibitor of P. carboxydovorans was also active on CO-DHs from Pseudomonas carboxydohydrogena, Acinetobacter sp. strain JC1, and Pseudomonas carboxydoflava. PMID- 2106506 TI - Genes for phycocyanin subunits in Synechocystis sp. strain PCC 6701 and assembly mutant UV16. AB - The cyanobacterial phycobilisome is a large protein complex located on the photosynthetic membrane. It harvests light energy and transfers it to chlorophyll for use in photosynthesis. Phycobilisome assembly mutants in the unicellular cyanobacterium Synechocystis sp. strain 6701 have been characterized. One such mutant, UV16, contains a defect in the assembly of the biliprotein phycocyanin. We report the cloning and sequencing of the phycocyanin genes from wild-type Synechocystis strain 6701 and demonstrate an alteration in the gene for the phycocyanin alpha subunit in UV16. Possible consequences of the lesion on phycobilisome assembly were assessed from its position in the phycocyanin tertiary and quaternary structures. The UV16 phenotype is complex and includes a reduced level of phycocyanin relative to that in the wild type. To determine whether the lower phycocyanin content results from lower transcript levels, a fragment of cpcBA was used as a probe for quantitating phycocyanin mRNA. Both the wild type and UV16 contained two phycocyanin transcripts of approximately 1.4 and 1.5 kilobases that were equal in abundance and that did not vary with light quality during cell growth. Equal levels of these transcripts in the wild type and UV16 suggest that the lower phycocyanin content in the mutant may be due to posttranscriptional events. The 5' ends of the two phycocyanin mRNAs were mapped at 100 and 223 base pairs upstream of the cpcB initiation codon. Homologous regions upstream of the putative transcription initiation sites may be important for maintaining high levels of transcription from the Synechocystis strain 6701 phycocyanin gene set. PMID- 2106507 TI - Structure and light-regulated expression of phycoerythrin genes in wild-type and phycobilisome assembly mutants of Synechocystis sp. strain PCC 6701. AB - Phycoerythrin is a major pigmented component of the phycobilisome, a cyanobacterial light-harvesting complex. It contains bilin-type chromophores that absorb and transfer light energy to chlorophyll protein complexes of the photosynthetic membranes. In many cyanobacteria, phycoerythrin expression is regulated by light wavelength in a response known as chromatic adaptation. Green light-grown cells contain higher levels of this biliprotein than do cells grown in red light. The phycoerythrin gene set from the unicellular cyanobacterium Synechocystis sp. strain PCC 6701 was cloned and sequenced, and the 5' end of the phycoerythrin mRNA was localized. The amino acid sequences of the phycoerythrin subunits from Synechocystis strain 6701 and Fremyella diplosiphon were 90% identical. As observed in F. diplosiphon, the Synechocystis strain 6701 phycoerythrin transcript accumulated to high levels in green light-grown cells and low levels in red light-grown cells. Similar nucleotide sequences, which might control gene expression, occurred upstream of the transcription initiation sites of the phycoerythrin genes in both organisms. While the phycoerythrin structure and light-regulated transcript accumulation were similar in Synechocystis strain 6701 and F. diplosiphon, the steady-state levels of phycoerythrin subunits during growth in red light were quite different for the two organisms. This observation suggests that control of phycoerythrin levels in Synechocystis strain 6701 is complex and may involve posttranscriptional processes. We also characterized the phycoerythrin genes and mRNA levels in two phycobilisome assembly mutants, UV16-40 and UV16. PMID- 2106508 TI - Characterization of the spoIVB and recN loci of Bacillus subtilis. AB - Two independent genes, recN and spoIVB, along with their respective promoter and termination regions, were discovered and sequenced in the 3.4-kilobase region between the ahrC and spoOA genes at map position 216 in the Bacillus subtilis chromosome map. The gene encoding a 576-amino-acid protein, which maintains a high homology with the Escherichia coli recN gene product, was adjacent to ahrC. The sequence revealed a 64,472-dalton polypeptide which contained a conserved ATP binding site and possible lexA-type regulatory binding sequences in its promoter region. A second open reading frame identified as the spoIVB gene was directly downstream of recN. It consisted of 1,275 nucleotides which coded for a 425-amino acid polypeptide with a molecular weight of 45,976. Phenotypic, genetic, and transcriptional analyses confirmed that this gene was spoIVB. Although no chloroform-resistant spores were produced by spoIVB-inactivated strains, under microscopic examination, phase-gray forespores were visible. The spoIVB165 mutation was localized to a 200-base-pair region in the amino-terminal portion of the polypeptide, spoIVB was not transcribed until hour 2 of sporulation in wild type B. subtilis cells, as determined by beta-galactosidase activity assays from lacZ transcriptional fusion constructions. We found no amino acid sequence homology between the spoIVB gene product and other known bacterial proteins. PMID- 2106509 TI - The CAM-OCT plasmid enhances UV responses of Pseudomonas aeruginosa recA mutants. AB - The effect of the CAM-OCT plasmid on responses to UV irradiation of Pseudomonas aeruginosa recA mutants was characterized. Mutant alleles examined included rec 1, rec-2, and recA7::Tn501. The plasmid substantially enhanced both survival and mutagenesis of RecA- cells after treatment with UV light. Survival of the RecA (CAM-OCT) cells after UV irradiation was intermediate between that seen in the wild-type P. aeruginosa PAO1 and the increased survival seen in PAO1(CAM-OCT) cells. Mutability was quantitated by the reversion to carbenicillin resistance of strains carrying a bla(Am) mutation on a derivative of plasmid RP1. UV-induced mutagenesis of CAM-OCT carrying recA mutants occurred at levels comparable to that seen in PAO1(CAM-OCT). The ability of CAM-OCT plasmid to suppress the recombination deficiency in recA mutants was tested by assaying for bacteriophage F116L-generalized transduction of a Tn7 insertion in the alkane utilization genes of CAM-OCT. Transduction of the Tn7 insertion was not detected in RecA-(CAM-OCT) strains but was easily seen in PAO1(CAM-OCT), indicating that the plasmid does not encode a recA analog. The results indicate that the CAM-OCT UV response genes are expressed in RecA- cells, which differs from results seen with other UV response-enhancing plasmids. The results suggest that CAM-OCT either encodes several UV responses genes itself or induces chromosomal UV response genes by an alternate mechanism. PMID- 2106511 TI - Regulation of formate dehydrogenase activity in Methanococcus thermolithotrophicus. AB - Methanococcus thermolithotrophicus can use either H2 or formate as the electron donor for methanogenesis from CO2. Resuspended-cell experiments revealed that the ability to use H2 as the source of electrons for methanogenesis was constitutive; cells grown on formate or H2-CO2 were equally capable of H2-CO2 methanogenesis. The ability to metabolize formate at high rates was observed only in cells previously grown on formate. Two such strains were distinguished: strain F and strain HF. Strain F was repeatedly grown exclusively on formate for over 3 years; this strain showed a constitutive capacity to metabolize formate to methane, even after subsequent repeated transfers to medium containing only H2-CO2. Strain HF could only metabolize formate to methane when grown in the presence of formate with no H2 present; this strain was recently derived from another strain (H) that had been exclusively grown on H2-CO2 and which upon initial transfer to formate medium could only metabolize formate to methane at a very slow rate. Initial adaptation of strain H to growth on formate was preceded by a long lag. The specific activities of hydrogenase and formate dehydrogenase in cell extracts derived from these different strains confirmed these findings. Similar levels of hydrogenase were observed in all strains, independent of the presence of H2 in the growth medium medium. High levels of formate dehydrogenase were also constitutive in strain F. Only low formate dehydrogenase activities were observed in strain H. High levels of formate dehydrogenase were observed in strain HF only when these cells were grown with formate in the absence of H2. In all strains the two- to threefold fluctuations of both hydrogenase and formate dehydrogenase cell free activities were observed during growth, with peak activities reached in the middle of the exponential phase. PMID- 2106510 TI - Transcription of the ftsZ gene and cell division in Escherichia coli. AB - The ftsZ gene of Escherichia coli, which lies in a cluster of cell division genes at 2 min on the genetic map, codes for a protein which is thought to play a key role in triggering cell division. Using an ftsZ::lacZ operon fusion, we have studied the transcription of the ftsZ gene under conditions in which cell division was either inhibited or synchronized in the bacterial population. In ftsZ, ftsA, ftsQ, and ftsI (or pbpB) mutants, there was no change in the differential rate of expression of the ftsZ gene in nonpermissive conditions, when cell division was completely blocked. Although the FtsZ protein is thought to be limiting for cell division, in synchronized cultures the ftsZ gene was expressed not only at the moment of septation initiation but throughout the cell cycle. Its expression, however, was not exponential but linear, with a rapid doubling in rate at a specific cell age; this age, about 20 min after division in a 60-min cycle, was different from the age at which the ftsZ::lacZ operon was duplicated. However, it was close to the age at which replication initiated and at which the rate of phospholipid synthesis doubled. During the transient division inhibition after a nutritional shift-up, ftsZ transcription again became linear, with two doublings in rate at intervals equal to the mass doubling time in the rich medium; it adopted the exponential rate typical of rich medium about 60 min after the shift-up, just before the bacterial population resumed cell division. The doubling in the rate of ftsZ transcription once per cycle in synchronized cultures and once per mass doubling time during the transition period after a nutritional shift-up reflects a new cell cycle event. PMID- 2106512 TI - Bacillopeptidase F of Bacillus subtilis: purification of the protein and cloning of the gene. AB - We have purified a minor extracellular serine protease from Bacillus subtilis. Characterization of this enzyme indicated that it was most likely the previously reported enzyme bacillopeptidase F. The amino-terminal sequence of the purified protein was determined, and a "guess-mer" oligonucleotide hybridization probe was constructed on the basis of that sequence. This probe was used to identify and clone the structural gene (bpr) for bacillopeptidase F. The deduced amino acid sequence for the mature protein (496 amino acids) was preceded by a putative signal sequence of 30 residues and a putative propeptide region of 164 amino acids. The bpr gene mapped near pyrD on the chromosome and was not required for growth or sporulation. PMID- 2106513 TI - Acquired thermotolerance and heat shock in the extremely thermophilic archaebacterium Sulfolobus sp. strain B12. AB - The extreme thermophile Sulfolobus sp. strain B12 exhibits an acquired thermotolerance response. Thus, survival of cells from a 70 degrees C culture at the lethal temperature of 92 degrees C was enhanced by as much as 6 orders of magnitude over a 2-h period if the culture was preheated to 88 degrees C for 60 min or longer before being exposed to the lethal temperature. In eubacteria and eucaryotes, acquired thermotolerance correlates with the induced synthesis of a dozen or so proteins known as heat shock proteins. In this Sulfolobus species, it correlates with the preferential synthesis of primarily one major protein (55 kilodaltons) and, to a much lesser extent, two minor proteins (28 and 35 kilodaltons). Since the synthesis of all other proteins was radically reduced and these proteins were apparently not degraded or exported, their relative abundance within the cell increased during the time the cells were becoming thermotolerant. They could not yet be related to known heat shock proteins. In immunoassays, they were not cross-reactive with antibodies against heat shock proteins from Escherichia coli (DnaK and GroE), which are highly conserved between eubacteria and eucaryotes. However, it appears that if acquired thermotolerance depends on the synthesis of protective proteins, then in this extremely thermophilic archaebacterium it depends primarily on one protein. PMID- 2106514 TI - High-frequency conjugal plasmid transfer from gram-negative Escherichia coli to various gram-positive coryneform bacteria. AB - We report on the mobilization of shuttle plasmids from gram-negative Escherichia coli to gram-positive corynebacteria mediated by P-type transfer functions. Introduction of plasmids into corynebacteria was markedly enhanced after heat treatment of the recipient cells. High-frequency plasmid transfer was also observed when the restriction system of the recipient was mutated. On the basis of our data, we conclude that efficient DNA transfer from gram-negative to gram positive bacteria, at least to coryneform bacteria, is conceivable in certain natural ecosystems. PMID- 2106515 TI - Fenfluramine augmentation of serotonin reuptake blockade antiobsessional treatment. AB - Seven patients who met DSM-III-R criteria for obsessive compulsive disorder and had only a partial response to the serotonin reuptake blockers fluoxetine, fluvoxamine, or clomipramine or were unable to tolerate therapeutic doses of these agents due to side effects underwent open treatment with fenfluramine augmentation. Fenfluramine is a serotonin releaser and reuptake blocker which is marketed as an anorectic agent. In doses of 20 to 60 mg/day, fenfluramine augmentation was well tolerated and resulted in a further decrease in obsessions and compulsions in six of these patients. Larger controlled studies are needed to confirm this finding. PMID- 2106516 TI - Riboflavin synthases of Bacillus subtilis. Purification and amino acid sequence of the alpha subunit. AB - Bacillus subtilis has two different riboflavin synthases characterized by the subunit structures alpha3 (light enzyme) and alpha3beta60 (heavy enzyme). The light enzyme was purified by a novel procedure with increased yield and excellent reproducibility. The proposed trimer structure was confirmed by cross-linking experiments with dimethyl suberimidate. Fragments of alpha subunits were prepared by cleavage with cyanogen bromide, trypsin, protease Lys-C, and Staphylococcus aureus protease V8, respectively. Sequences were determined by automated liquid or gas phase Edman degradation. The complete sequence (202 amino acids) was established by direct sequencing of the N terminus and sequencing of overlapping peptides. The sequence shows marked internal homology between the NH2-terminal and COOH-terminal half encompassing 26 identical positions and 23 conservative replacements. This suggests that the protomer forms two structurally similar domains. Since it is known that the enzyme has two binding sites per subunit for the substrate 6,7-dimethyl-8-ribityllumazine, it appears likely that each of the homologous protein domains provides one binding site. The stereochemical features of the enzyme mechanism and the structural relation of the alpha trimer to the beta60 capsid of heavy riboflavin synthase suggest that the six domains corresponding to the alpha subunit trimer are related by pseudo 32 symmetry. PMID- 2106517 TI - Terbium as a luminescent probe of metal-binding sites in protein kinase C. AB - In the present report, we demonstrate that Tb3+ binds to protein kinase C and serves as a luminescent reporter of certain cationic metal-binding sites. Tb3+ titration of 50 nM protein kinase C results in a 20-fold enhancement of Tb3+ luminescence which is half-maximal at 12 microM Tb3+. A Kd of approximately 145 nM was determined for Tb3+ binding to the enzyme. The excitation spectrum of bound Tb3+ exhibits a peak at 280 nm characteristic of energy transfer from protein tryptophan or tyrosine residues. The luminescence of this complex can be markedly decreased by other metals, including Pb2+ (IC50 = 25 microM), La3+ (IC50 = 50 microM), Hg2+ (IC50 = 300 microM), Ca2+ (IC50 = 6 mM), and Zn2+ (IC50 greater than 10 mM), and chelation of Tb3+ by 2 mM EGTA. Tb3+ binding to protein kinase C is correlated with its inhibition of protein kinase activity (IC50 = 8 microM), r = 0.99) and phorbol ester binding (IC50 = 15 microM, r = 0.98). Tb3+ inhibition of protein kinase C activity cannot be overcome by excess Ca2+, but can be partially overcome with excess phosphatidylserine or by chelation of Tb3+ with EGTA. Tb3+ noncompetitively inhibits phorbol ester binding by decreasing the maximal extent of binding without significantly altering binding affinity. The results suggest that the Tb3(+)-binding site is at or allosterically related to the enzyme's phosphatidylserine-binding site, but is distinct from the phorbol ester-binding domain and the Ca2(+)-binding site that regulates enzyme activity. PMID- 2106518 TI - Hormonally inducible phosphorylation of a nuclear pool of ribosomal protein S6. AB - Thyrotropin releasing hormone (TRH) and epidermal growth factor induce the rapid phosphorylation of a basic, chromatin-associated protein present in GH4 rat pituitary cells and also found in primary hepatocyte culture. Cell fraction experiments indicate a nucleolar localization for this basic, chromatin associated protein. The protein has been purified to homogeneity from rat liver and 23 amino acids of its N-terminal sequence determined. There is complete homology between the sequenced portion of the basic, chromatin-associated protein and the N-terminal sequence of rat ribosomal protein S6. In vivo and in vitro phosphorylation, two-dimensional gel analysis and two-dimensional tryptic phosphopeptide mapping support the identity of the basic, chromatin-associated protein and S6. Our experimental data indicate the existence of a nuclear pool of S6 whose phosphorylation is hormone inducible. PMID- 2106519 TI - In vitro kinetic analysis of the role of the positive charge at the amino terminal region of signal peptides in translocation of secretory protein across the cytoplasmic membrane in Escherichia coli. AB - By using an in vitro system for the translocation of secretory proteins in Escherichia coli, detailed and quantitative studies were performed as to the function of the positively charged amino acid residues at the amino terminus of the signal peptide. Uncleavable OmpF-Lpp, a model secretory protein carrying an uncleavable signal peptide, and mutant proteins derived from it were used as translocation substrates. When the positive charge, +2 (LysArg) for the wild type, was changed to 0, -1, or -2, little or no translocation was observed. The number of the positive charge was altered by introducing different numbers of Lys or Arg residues into the amino terminus. The rate of translocation was roughly proportional to this number, irrespective of whether the charged amino acid residues were Lys or Arg. When the amino-terminal LysArg was replaced by His residues, translocation took place more efficiently at pH 6.5 than pH 8.0, whereas that of the wild-type was about the same as the two pH values. We conclude that the signal peptide requires a positive charge at its amino-terminal region to function in the translocation reaction and that the rate of translocation is roughly proportional to the number of the positively charged group, irrespective of the amino acid species that donates the charge. Evidence suggesting that the positive charge is involved in the binding of precursor proteins to the membrane surface to initiate translocation is also presented. PMID- 2106520 TI - Purification of cholesterol 7 alpha-hydroxylase from human and rat liver and production of inhibiting polyclonal antibodies. AB - Cholesterol 7 alpha-hydroxylase, the cytochrome P-450-dependent and rate controlling enzyme of bile acid synthesis, was purified from rat and human liver microsomes. The purified fractions were assayed in a reconstituted system containing [4-14C]cholesterol, and cholesterol 7 alpha-hydroxylase activities in these fractions increased 500-600-fold relative to whole microsomes. Polyacrylamide gel electrophoresis of rat microsomes followed by immunoblotting with polyclonal rabbit antisera raised against purified cholesterol 7 alpha hydroxylases revealed two peaks at molecular masses of 47,000 and 49,000 daltons for both rat and human fractions. Increasing amounts of rabbit anti-rat and anti human antibodies progressively inhibited rat microsomal cholesterol 7 alpha hydroxylase activity up to 80%. In contrast, monospecific antibodies raised against other purified cytochrome P-450 enzymes (P-450f, P-450g, and P-450j) did not inhibit rat or human cholesterol 7 alpha-hydroxylase activity. Immunoblots of rat microsomes with the rabbit anti-rat cholesterol 7 alpha-hydroxylase antibody demonstrated that the antibody reacted quantitatively with the rat microsomal enzyme. Microsomes from cholesterol-fed rats showed increased cholesterol 7 alpha hydroxylase mass, whereas treatment with pravastatin, an inhibitor of hydroxy methylglutaryl-coenzyme A reductase, reduced enzyme mass. Microsomes from starved rats contained slightly less cholesterol 7 alpha-hydroxylase protein than chow fed control rats. These results indicate a similarity in molecular mass, structure, and antigenicity between rat and human cholesterol 7 alpha hydroxylases; demonstrate the production of inhibiting anti-cholesterol 7 alpha hydroxylase antibodies that can be used to measure the change in cholesterol 7 alpha-hydroxylase enzyme mass under various conditions; and emphasize the unique structure of cholesterol 7 alpha-hydroxylase with respect to other cytochrome P 450-dependent hydroxylases. PMID- 2106521 TI - Growth regulation of A431 cells. Modulation of expression of transforming growth factor-alpha mRNA and 2',5'-oligoadenylate synthetase activity. AB - To explore bidirectional regulatory interactions between interferons and autocrine polypeptide factors, we examined the modulation of expression of transforming growth factor-alpha and 2',5'-oligoadenylate synthetase activity in A431 epidermoid carcinoma cells after treatment with interferon-gamma and transforming growth factor-alpha. Treatment of A431 cells with interferon-gamma increased steady state levels of transforming growth factor-alpha mRNA by 4-fold and increased the levels of transforming growth factor-alpha in the culture medium. There were additive growth inhibitory effects upon coaddition of exogenous transforming growth factor-alpha and interferon-gamma to the cultures. Addition of transforming growth factor-alpha to A431 cell cultures in the absence of interferon could stimulate the induction of 2',5'-oligoadenylate synthetase activity by more than 2-fold. These findings demonstrate that the induction of transforming growth factor-alpha in interferon-gamma-treated A431 cells could act to regulate interferon-induced gene(s), e.g. 2',5'-oligoadenylate synthetase, suggesting interactions between a potential autocrine growth factor and the interferon system in the growth regulation of A431 cells. PMID- 2106522 TI - Regulation of S6 kinase activity in Madin-Darby canine kidney renal epithelial cells. AB - Mitogenic stimulation of mammalian cells results in increased serine phosphorylation of ribosomal protein S6. Phorbol esters, which stimulate protein kinase C activity, can also increase S6 phosphorylation. In order to further investigate the role of protein kinase C in the activation S6 kinase, we studied the stimulation of an S6 kinase activity in response to phorbol ester and epinephrine in a renal epithelial cell line, Madin-Darby canine kidney cells (MDCK). In these cells, S6 phosphorylating activity in cytosolic extracts was increased following the addition of phorbol ester to the intact cells. S6 kinase and protein kinase C activities were measured in separate fractions prepared by DEAE-Sephacel fractionation of cytosolic extracts prepared from the same cells. The time course and dose-response curves for the effects of phorbol 12-myristate 13-acetate (PMA) on S6 kinase activity were similar to those for its effects on protein kinase C binding to the membrane fraction, indicating that S6 kinase activation was correlated with protein kinase C activation. Epinephrine, acting via alpha1-adrenergic receptors, also stimulated S6 kinase activity in MDCK cells; the magnitude of this effect was similar to that of PMA. However, epinephrine causes only a slight and transient association of protein kinase C with the membrane. The effect of epinephrine on S6 kinase activity, unlike that of PMA, was dependent on the presence of extracellular calcium. A23187, a calcium ionophore, could also stimulate S6 kinase activity. These results suggest that S6 kinase can be activated through more than one signaling pathway in MDCK cells. The properties of the PMA-stimulated S6 kinase were further investigated following partial purification of the enzyme. The S6 kinase was distinct from protein kinase C by several criteria. Noteably, the S6 kinase was highly specific for S6 as substrate. These results show that phorbol esters, acting through protein kinase C, stimulate the activity of a unique S6 kinase. This S6 kinase can also be activated through a signaling pathway that appears to be dependent on increased intracellular calcium. PMID- 2106523 TI - Mouse "protective protein". cDNA cloning, sequence comparison, and expression. AB - The "protective protein" is the glycoprotein that forms a complex with the lysosomal enzymes beta-galactosidase and neuraminidase. Its deficiency in man leads to the metabolic storage disorder galactosialidosis. The primary structure of human protective protein, deduced from its cloned cDNA, shows homology to yeast serine carboxypeptidases. We have isolated a full-length cDNA encoding murine protective protein. The nucleotide sequences as well as the predicted amino acid sequences are highly conserved between man and mouse. Domains important for the protease function are completely identical in the two proteins. Both human and mouse mature protective proteins covalently bind radiolabeled diisopropyl fluorophosphate. Transient expression of the murine cDNA in COS-1 cells yields a protective protein precursor of 54 kDa, a size characteristic of the glycosylated form. This cDNA-encoded precursor, endocytosed by human galactosialidosis fibroblasts, is processed into a 32- and a 20-kDa heterodimer and corrects beta-galactosidase and neuraminidase activities. A tissue-specific expression of protective protein mRNA is observed when total RNA from different mouse organs is analyzed on Northern blots. PMID- 2106525 TI - A role for endogenous arachidonate metabolites in the regulated expression of the 25-hydroxyvitamin D-1-hydroxylation reaction in cultured alveolar macrophages from patients with sarcoidosis. AB - In the human granulomatous disease sarcoidosis hypercalcemia and/or hypercalciuria result from the endogenous overproduction of 1,25-dihydroxyvitamin D [1,25-(OH)2D] by the disease-activated macrophage. Unlike the renal 25-hydroxy vitamin D (25OHD)-1-hydroxylase, normally the sole synthetic source of the hormone in man, the 25OHD3-1-hydroxylation reaction in cultured pulmonary alveolar macrophages (PAM) from patients with sarcoidosis is subject to stimulation by the immune cytokine interferon-gamma (IFN gamma) and inhibition by the antiinflammatory glucocorticoid dexamethasone. The data presented here suggest that IFN gamma and calcium ionophore A23187 promote enhanced expression of the sarcoid PAM 25OHD3-1-hydroxylation reaction by increasing endogenous arachidonic acid metabolism through the 5-lipoxygenase pathway. Dexamethasone, an inhibitor of the cellular phospholipase-A2-arachidonic acid-generating system, and BW755C, a lipoxygenase pathway inhibitor, inhibited PAM 1,25-(OH)2D3 synthesis by 64% and 54%, respectively. Conversely, leukotriene C4, a distal metabolite in the arachidonic acid 5-lipoxygenase pathway, increased the hydroxylation reaction by 234% and restored dexamethasone-inhibited PAM 1,25 (OH)2D3 synthetic activity. The results of this study provide presumptive evidence for an important role of agonist (IFN gamma)-calcium-modulated eicosanoid metabolism in the regulated synthesis of 1,25-(OH)2D by PAM in sarcoidosis. PMID- 2106524 TI - Ciliary microtubule capping structures contain a mammalian kinetochore antigen. AB - Structures that cap the plus ends of microtubules may be involved in the regulation of their assembly and disassembly. Growing and disassembling microtubules in the mitotic apparatus are capped by kinetochores and ciliary and flagellar microtubules are capped by the central microtubule cap and distal filaments. To compare the ciliary caps with kinetochores, isolated Tetrahymena cilia were stained with CREST (Calcinosis/phenomenon esophageal dysmotility, sclerodactyly, telangiectasia) antisera known to stain kinetochores. Immunofluorescence microscopy revealed that a CREST antiserum stained the distal tips of cilia that contained capping structures but did not stain axonemes that lacked capping structures. Both Coomassie blue-stained gels and Western blots probed with CREST antiserum revealed that a 97-kD antigen copurifies with the capping structures. Affinity-purified antibodies to the 97-kD ciliary protein stained the tips of cap-containing Tetrahymena cilia and the kinetochores in HeLa, Chinese hamster ovary, and Indian muntjak cells. These results suggest that at least one polypeptide found in the kinetochore is present in ciliary microtubule capping structures and that there may be a structural and/or functional homology between these structures that cap the plus ends of microtubules. PMID- 2106526 TI - Serum bioactive follicle-stimulating hormone levels in girls with precocious sexual development. AB - We studied the serum immunoreactive (immuno) and bioactive (bio) FSH concentrations in 16 prepubertal children (1.3-9 yr old), 6 girls with premature thelarche (0.8-2 yr old), and 9 girls with central precocious puberty (2.5-9.3 yr old). The serum bio-FSH was measured by the granulosa cell aromatase bioassay. The basal serum bio-FSH levels were not significantly different in patients with central precocious puberty (6.4 +/- 1.5 IU/L), premature thelarche (7.5 +/- 0.5 IU/L), and prepubertal controls (4.4 +/- 0.7 IU/L). However, the peak responses of both serum immuno- and bio-FSH levels to iv GnRH were higher in patients with premature thelarche (immuno-FSH, 29.3 +/- 2.3 IU/L; bio-FSH, 100.7 +/- 12.2 IU/L) than in those with central precocious puberty [immuno-FSH, 17.5 +/- 3.1 IU/L (p less than 0.05); bio-FSH, 42.4 +/- 9.8 IU/L (p less than 0.01)]. This suggests that in children with premature thelarche, there is a predominant immuno- as well as bio-FSH response to GnRH. After 12 months of GnRH agonist therapy, both serum immuno- and bio-FSH levels were suppressed in patients with central precocious puberty. The differences in clinical presentation between central precocious puberty and premature thelarche cannot be explained by the differences in FSH bioactivity. PMID- 2106527 TI - Suppression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in the polycystic ovary syndrome. AB - Women with the polycystic ovary syndrome (PCO) have significant insulin resistance and are at risk to develop noninsulin-dependent diabetes mellitus. It remains controversial, however, whether hyperandrogenism directly decreases insulin action. Hence, we performed 2-h euglycemic glucose (approximately 772 pmol/L steady state insulin levels) clamps in nine PCO women with insulin resistance basally and after the 12th week of therapy with a superagonist GnRH analog (40 micrograms every 8 h, sc). Diet, activity, and weight were kept constant. Despite significant decreases in plasma testosterone and androstenedione levels (both P less than 0.05), there was no significant change in insulin-mediated glucose disposal, plasma insulin levels, or hepatic glucose production. The sample size was adequate to detect a clinically significant change in insulin-stimulated glucose disposal (i.e. approximately 3.3 mumol/kg.min; P less than or equal to 0.05). We conclude that suppressing androgen levels into the normal range did not result in significant changes in insulin resistance in PCO. Thus, controlling hyperandrogenemia is not a clinically effective modality to improve insulin action and thereby decrease the risk of noninsulin-dependent diabetes in PCO. PMID- 2106528 TI - Effect of cholinergic muscarinic receptor blockade on human growth hormone (GH) releasing hormone-(1-44)-induced GH secretion in anorexia nervosa. AB - The presence of hypothalamic disturbances affecting GH secretion in anorexia nervosa has been suggested, although a normal GH response to GH-releasing hormone (GHRH) administration has been shown in these patients. The present study was performed to investigate the role of acetylcholine in regulating GH secretion by using pirenzepine, which selectively blocks muscarinic cholinergic receptors. Paired tests were performed in nine anorexia nervosa patients (age +/- SEM, 19.1 +/- 1.2 yr; percent ideal body weight, -32.7 +/- 2.2%) and in six normal controls (20.1 +/- 0.3 yr; -3.1 +/- 1.8%). GHRH-(1-44) (1 microgram/kg) was infused iv with and without pirenzepine pretreatment (0.6 mg/kg, iv). Basal levels of GH were not different in anorexia nervosa compared to normal controls, whereas, somatomedin-C levels were significantly lower in anorexia nervosa patients. However, after pirenzepine administration, the GHRH-stimulated GH responses were completely blocked in normal controls, but not in anorexia nervosa patients. These results suggested that altered muscarinic cholinergic mechanism are involved in the modulation of GH secretion in patients with anorexia nervosa. PMID- 2106530 TI - Free light chains of immunoglobulins in the cerebrospinal fluid of human immunodeficiency virus type 1-infected patients. AB - The presence of immunoglobulin (Ig) free light chains (FLC) was investigated in the cerebrospinal fluid (CSF) of human immunodeficiency virus type 1 (HIV-1) infected patients. Intrathecal synthesis of FLC was demonstrated in 80% of the patients, even in the absence of oligoclonal Ig. The FLC patterns were characterized by restricted heterogeneity with regard to both isoelectric point and the molecular weight, and were mainly composed by dimers rather than monomers. A striking prevalence of lambda FLC was also observed. Local production of FLC can be taken as a marker of an ongoing immunopathological process within the central nervous system (CNS) in HIV-1-infected patients. A deregulation of Ig production by intrathecally activated B cells may be hypothesized. PMID- 2106529 TI - Growth hormone responses to oral glucose loading measured by highly sensitive enzyme immunoassay in normal subjects and patients with glucose intolerance and acromegaly. AB - Plasma GH levels were determined during a 75-g oral glucose tolerance test using a highly sensitive enzyme immunoassay. Most normal subjects and patients with varying degrees of impaired glucose tolerance showed a decrease in plasma GH levels during the first 60 min. A GH rise within 60 min was observed in 3 of 37 normal subjects. The incidence of the GH rise (8%) was significantly lower than that (40%) in control experiments after water loading. The median minimum GH levels were 0.15 and 0.14 micrograms/L after glucose and water loading, respectively. Plasma GH responses to glucose ingestion were not different between normal subjects and patients with glucose intolerance. After surgery, 12 of 16 patients with acromegaly showed low basal GH levels (less than 5.0 micrograms/L). Six of the 12 patients showed normal GH responses to glucose loading (median minimum GH level, 0.21 micrograms/L) and normal plasma insulin-like growth factor I levels. Plasma GH levels were not suppressed below 1.0 micrograms/L in the remaining 6 acromegalic patients. Determination of plasma GH levels after glucose loading by the highly sensitive enzyme immunoassay is useful for evaluating the effect of surgical treatment of acromegaly. PMID- 2106531 TI - Interferon-gamma enhances the expression of retinal S-antigen, a specific neuronal cell marker. AB - Interferon-gamma (IFN-gamma) is a potent lymphokine which can modify a variety of cellular processes. One of the mechanisms involved in these processes is the ability of IFN-gamma to alter the regulation and expression of cellular proteins. Using analytical flow cytometry, we show that recombinant human IFN-gamma can enhance the expression of retinal S-antigen in retinoblastoma cells. This enhancement was selective since two other retinal cell proteins, interphotoreceptor binding protein (IRBP) and photo-6, were not affected by IFN gamma treatment. Retinal S-antigen plays an important role in vision and is one of the retinal proteins capable of inducing an inflammatory eye disease called experimental autoimmune uveitis. These studies therefore demonstrate an important role for this lymphokine, that is, the enhanced expression of a neuronal cell protein. This finding may also identify additional mechanisms by which IFN-gamma may participate in immunopathologic events in nervous tissue. PMID- 2106532 TI - Appraising the quality of drug-evaluation research: II. A methodological review procedure for prophylactic treatment trials. AB - The present paper describes a methodological review procedure for evaluating a body of research focusing on the study of a prophylactic treatment medication. An illustrative application of this procedure to research evaluating lithium prophylaxis for bipolar affective disorders revealed possible biases in respect to subject selection, and general problems with diagnostic reliability and the reliability of the dependent variable. A tendency to ignore the statistical power aspects of determining sample size was also noted, along with possible difficulties relating to infrequent assessments of patients' clinical conditions. The implications of these matters were discussed in terms of the unique vantage point offered by this methodological review process. PMID- 2106533 TI - Adjunctive clonazepam for maintenance treatment of bipolar affective disorder. AB - In light of the reported efficacy of clonazepam in treating acute mania, we conducted a retrospective review of clinical experience with this agent in maintenance treatment of patients with bipolar affective disorder. Twenty patients with bipolar affective disorder treated with adjunctive clonazepam were identified. A case vignette and summary data on all 20 patients are presented. Clonazepam had been prescribed, in a manner similar to neuroleptics, as part of the maintenance regimen and/or on an as needed basis for acute exacerbations. In six of 17 patients previously receiving combined lithium and neuroleptic treatment, clonazepam successfully replaced the neuroleptic. Overall, eight patients were rated much improved or very much improved, including three of the five cases initially rated most severely ill. Possible mechanisms and treatment strategies are discussed. PMID- 2106534 TI - Change in haloperidol level due to carbamazepine--a complicating factor in combined medication for schizophrenia. AB - Serum haloperidol levels were measured in patients who received haloperidol alone and, subsequently, haloperidol in combination with carbamazepine or lithium carbonate. Haloperidol levels and the level- dose ratios dropped about 50% in patients receiving carbamazepine. They remained the same in most patients receiving lithium carbonate. One patient receiving added carbamazepine experienced worsening of symptoms; this was associated with a drop in serum haloperidol level. Two other patients receiving added carbamazepine showed significant symptom reduction, although they also sustained drops in serum haloperidol levels. It is not clear whether these two individuals benefited from a primary antipsychotic effect of carbamazepine or from reduction of "toxic" haloperidol levels. Serum levels of antipsychotic medication should be monitored carefully when these medications are prescribed in combination with carbamazepine. PMID- 2106535 TI - The effect of testing on the reported incidence of medication errors in a medical center. AB - This study explores the impact of eliminating a yearly medication test on the medication error rate reported on both incident reports and questionnaires and describes nurse-identified strategies that may prevent medication errors. Results indicate that eliminating the annual medication test does not significantly change the overall medication error rate. However, the number of errors involving the administration of a medication to the wrong patient has increased significantly. More medication errors have been reported on the questionnaires than on the incident reports. Four factors have been identified by the nurses as being helpful in preventing medication errors. Several limitations of this study dictate that the results be applied with caution. However, in this setting, the use of an annual medication test as a strategy for reducing medication errors has not been supported. PMID- 2106536 TI - Committee work: serendipitous teaching and learning. AB - This study describes what registered nurses incidentally teach and learn while serving on a committee of a professional nursing organization. One hundred fifteen nurses were asked to complete a questionnaire eliciting information about teaching and learning during District committee meetings. A total of 46 questionnaires were returned for a response rate of 40%. Learning was reported more than teaching during committee meetings. The greatest number of situations described by the respondents as "incidental learning" consisted of group discussion and group work on projects. The nurses obtained new information, gained psychomotor skills, and increased their ability to work effectively in groups. The nurses "helped teach," "educated," and "passed on knowledge," but they referred more often to sharing and contributing than teaching. The findings of this study suggest that, indeed, teaching and learning occur during committee meetings, making these gatherings an adult educational method. PMID- 2106537 TI - Continuing education electronic bulletin board system: provider readiness and interest. AB - This study explored the feasibility of establishing a computer-based, statewide electronic bulletin system (BBS) for continuing education for nurses in Florida. An anonymous survey addressing the feasibility of instituting such a BBS was mailed to a random stratified sample of 225 continuing education providers approved by the Florida Board of Nursing. The survey explored information services used and desired by providers, availability of resources to use a BBS, fees providers would be willing to pay, and the degree of interest in participating in a BBS. The findings of this preliminary study suggest that although support for a BBS featuring continuing education for nurses may be emerging in Florida, two major impediments to the establishment of such a system currently exist: start up and maintenance costs, and the nursing profession's lack of preparedness. PMID- 2106538 TI - Learning style theory and patient education. AB - This article argues for the use of learning style theory in patient education. Although nurses need to have a repertoire of teaching strategies as well as possess flexibility in teaching clients, research has demonstrated that nurses do not understand teaching and learning principles. This article discusses the theoretical tenets of Kolb's learning style theory and applies this theory to patient education. PMID- 2106539 TI - Nursing model encourages care planning. AB - After examining the pitfalls of nursing care plans done in a medical model format, a system based entirely on the nursing model was developed in a 500-bed acute care hospital. By centering the format, the structure, and the education around the patient problems treated by nurses, the nurses in this hospital began to do care plans for the purpose of improving patient care rather than for compliance with the Joint Commission on Accreditation of Healthcare Organizations' regulations. The system has led to more knowledgeable nurses and a more autonomous and rewarding practice setting. PMID- 2106540 TI - Reasons why emergency nurses take or do not take the certification examination in emergency nursing. AB - The purpose of this descriptive, exploratory study was to identify reasons that motivate the emergency nurse to take the Certification Exam for Emergency Nursing (CEN exam); reasons certified emergency nurses (CEN) give concerning their decisions to recertify; and a comparison of demographic characteristics in relation to these reasons. A random sample of 500 registered nurses who are currently members of the Emergency Nurses Association (ENA) and who are working in the emergency department was obtained from the ENA. These nurses received a questionnaire packet containing a cover letter explaining the purpose of the study, a combined Educational Participation Scale (EPS) and Deterrents to Participation Scale (DPS), a personal data questionnaire, and a return envelope. PMID- 2106541 TI - Brief: RN students in baccalaureate programs--faculty's role and responsibility. PMID- 2106542 TI - To discover is to learn: a class on the nurse as educator. PMID- 2106543 TI - Retain expert nurses through clinical ladder alternatives. AB - The nursing shortage, recruitment, and retention are critical issues relevant to the healthcare delivery system. These issues have been well documented throughout nursing literature. Retention of the clinical expert in the profession is crucial to maintaining a high standard of patient care. Clinical ladder programs address these issues by recognizing and rewarding excellence. However, development of such programs can be cumbersome, complicated, and expensive, and has not been documented as definitively effective. This article describes the development of an alternative approach to this traditional clinical ladder, and Staff Development's role in facilitating such a program. PMID- 2106544 TI - Decision analysis in clinical cardiology: when is coronary angiography required in aortic stenosis? AB - Decision analysis offers a reproducible, explicit approach to complex clinical decisions. It consists of developing a model, typically a decision tree, that separates choices from chances and that specifies and assigns relative values to outcomes. Sensitivity analysis allows exploration of alternative assumptions. Cost-effectiveness analysis shows the relation between dollars spent and improved health outcomes achieved. In a tutorial format, this approach is applied to the decision whether to perform coronary angiography in a patient who requires aortic valve replacement for critical aortic stenosis. PMID- 2106545 TI - Abnormal liver function in malnourished patients receiving total parenteral nutrition: a prospective randomized study. AB - A prospective study was performed in clinically malnourished patients in which liver function was tested during a 4-week period of total parenteral nutrition (TPN). The purpose was to determine if concomitant intravenous lipid administration would reduce liver function abnormalities noted to occur frequently in patients receiving TPN. Twenty-five patients were randomly assigned to receive either daily infusions of 200 cc of a 20% lipid emulsion with TPN or TPN without lipid for the first week. In the subsequent 3 weeks all patients received daily intravenous lipid. The early lipid treatment group received 0.7 g lipid/kg BW/day and approximately 280 mg of choline/day from the lecithin emulsifier throughout the entire study period. Liver function tests were performed twice in the first week, then weekly thereafter. There were significant (p less than 0.05) elevations in liver function tests in the early lipid treatment group (for aspartate aminotransferase in weeks 1, 2, and 3, and lactic acid dehydrogenase in weeks 2 and 3). Alkaline phosphatase activity was elevated at weeks 2, 3, and 4 for the lipid-treatment group and at week 1 for the lipid restricted group. The two groups had a similar elevation in gamma glutamyltransferase activity. Analysis of covariance demonstrated that the overall duration of TPN, and not the presence or absence of intravenous lipid, was significantly related to the elevations in both alkaline phosphatase and gamma-glutamyltransferase (GGT) levels. In contrast, the early intravenous administration of lipid was significantly related to the increase in aspartate aminotransferase levels. The peak increase in AST was noted at day 7 in the lipid administration group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106546 TI - General and specialized parenteral amino acid formulations for nutrition support. AB - Advances in the understanding of amino acid metabolism and of the interaction of amino acids with skeletal muscle, liver, brain, and other tissues have led to refinements of parenteral amino acid solutions. Clinical situations may dictate the use of specific amino acid formulations. Branched-chain amino acid (BCAA) solutions may normalize aberrant amino acid profiles in patients with hepatic encephalopathy; however, controlled trials demonstrate little effect on clinical outcome, and the effectiveness in patients with acute liver failure or undergoing orthotopic liver transplantation is unproved. BCAA solutions have also been tried in septic and severely stressed patients with equivocal results. Renal failure has been treated with essential amino acid solutions, yet low-dose standard amino acid formulations are probably equally effective. Pediatric preparations have been tailored to "normalize" amino acid profiles to those of healthy term, breast fed neonates. Recent studies suggest that premature infants receiving these formulations may achieve intrauterine growth rates, although the effect on long term outcome is unknown. Glutamine may be essential for the preservation of intestinal mucosal structure and function; further study is indicated to determine the necessity of adding glutamine to parenteral amino acid solutions. Recently, amino acid infusions have been associated with enhanced ventilatory drive, possibly via stimulation of central ventilatory mechanisms. A variety of other side effects have been documented, including acidosis, hyperammonemia, hypercalciuria, and possibly bone disease and hepatotoxicity. Further understanding of the metabolism of intravenous infusion of amino acids is necessary to provide optimal nutritional protein support. Because full information regarding the complex effects of intravenous substrates is lacking, special amino acid formulations must be used with caution. PMID- 2106547 TI - Leukotriene inhibitors modulate hepatic injury induced by lipopolysaccharide activated macrophages. AB - In an attempt to elucidate the effect of lipoxygenase inhibitors on hepatic injury, we investigated D-galactosamine (GalN)-treated C57BL/6 mice receiving an intravenous (i.v.) injection of lipopolysaccharide (LPS)-activated autologous spleen cells. As compared with control spleen cells, the number of monocytes in the spleen cells isolated from LPS-treated mice and their oxidative free radical production increased markedly. Oxygen radical production by the dish-adherent cells (macrophage-rich population) was enhanced a further 4-fold. Although hepatotoxicity was not demonstrated in mice treated with 20 mg GalN alone, marked hepatic injury was found in the GalN-treated mice with a supplementation of LPS activated spleen cells. The dish-adherent cells aggravated this hepatic injury, in contrast to minor hepatotoxicity by the nonadherent cells. Oxygen radical production by LPS-activated spleen cells was markedly reduced by the lipoxygenase inhibitors (azelastine, ketotifen and AA861). Hepatotoxicity was scarcely detected in the GalN-treated mice with a supplementation of the LPS-activated spleen cells which had been previously treated with lipoxygenase inhibitors. From these results, LPS-activated spleen macrophages contributed to hepatic injury induced by GalN, and lipoxygenase inhibitors which reduced oxygen radical production by the activated cells, protected against macrophage-induced hepatic injury in mice. PMID- 2106548 TI - Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non B and frequency of circulating antibodies to hepatitis C virus (HCV). AB - The natural course of chronic hepatitis non-A, non-B (HNANB) was documented for 3 20 yr (mean 8 yr) in 86 patients, who attended our special ambulance between 1981 and 1988. Sixty five of the 86 patients (75%) were positive for circulating antibodies against hepatitis C virus (HCV) (anti-HCV). Twenty four patients had chronic posttransfusion (PT)-HNANB (18 anti-HCV-positive; 75%), and 62 patients had sporadic (S)-HNANB (47 anti-HCV-positive; 75%). Twenty nine per cent of patients with chronic PT-HNANB had sustained normalization of aminotransferases after a period up to 5 yr, 55% demonstrated chronic persistent hepatitis (CPH) and 16% progressed to chronic active hepatitis (CAH) with transition to cirrhosis. In the group with chronic S-HNANB, 2% of patients showed remission, 43% had stable CPH and 55% progressed to CAH or cirrhosis. However, development of cirrhotic complications required many years. Transition from CAH to CPH or remission was not observed. The results indicate that 75% of both patients groups with chronic PT- and S-HNANB are infected with the same agent, of which antibodies are detected by the new anti-HCV assay. There was no statistical association between the severity of the disease and the presence of anti-HCV. The different proportions of progressive courses in chronic PT- and S-HNANB might be explained by the patient recruitment. PMID- 2106549 TI - The significance of infections with two types of viral hepatitis demonstrated by histologic features in chimpanzees. AB - In view of the recognized importance of necroinflammatory episodes in chronic hepatitis B virus (HBV) infection, chimpanzees, either HBV surface antigen (HBsAg) carriers or noninfected (naive), were infected with other primary hepatotropic viruses to evaluate histologic alterations and changes in virologic and biochemical markers of infection. The advantages of studies on chimpanzees are the availability of serial biopsy specimens and the viral type-specific histologic lesions, not as well recognized in humans. Infection with hepatitis A and non-A, non-B (NANB) agents produced more severe lesions in chronic HBsAg carrier chimpanzees than in naive animals. During this superinfection, the specific expression of the second agent was predominant, indicating that the exacerbation is caused by the second agent, but that carriers are prone to more severe disease than the naive chimpanzees. Hepatitis delta virus (HDV) infections were always coexistant with HBV and superinfection of carriers produced histologic changes more severe than those seen in any other type of viral hepatitis. Such HDV infections revealed less evidence of lymphocytotoxicity but rather of cytotoxicity, and sometimes resembled in appearance the histopathology of NANB. Coinfection of HDV and HBV and superinfection of HBV-carriers with NANB resulted in hepatitis that was far less severe than superinfection of HDV in HBV carriers, greatly in keeping with human experiences. HBV replication was suppressed transiently in both NANB and HDV superinfection. This implies that in exacerbations during chronic HBV infections of humans, suppression of HBV replication markers indicates superinfection, for instance, by NANB for which markers are so far not widely available; by contrast, elevated markers of HBV replication suggest reactivation of the original HBV infection. PMID- 2106550 TI - Approach to immunization in the immunosuppressed host. AB - An ever-increasing population of immunocompromised individuals, including not only the burgeoning AIDS population but also those patients whose host defenses have been damaged by a wide variety of diseases and their therapies, requires prophylaxis against infectious diseases. Existing vaccines can provide some benefit, but the clinician must always be alert to the fact that vaccine response cannot be assumed and such adjunctive measures as antimicrobial prophylaxis (i.e., amantadine during community-wide influenza outbreaks or penicillin prophylaxis against pneumococcal infection in certain asplenics) and/or intravenous immunoglobulin administration should be considered in some patients. In the future, in addition to developing new vaccines, a major effort should be devoted to the development of immunoadjuvants that would increase the effectiveness of vaccine administration. PMID- 2106551 TI - IL-2 gene inducibility in T cells before T cell receptor expression. Changes in signaling pathways and gene expression requirements during intrathymic maturation. AB - The ability to express the growth hormone IL-2 upon stimulation gives T lymphocytes one of their major effector functions in the immune system. IL-2 is apparently synthesized only by T cells, and only by a subset of T cells which constitutes a "helper" class. It remains unknown how and when the IL-2-producing lineage becomes distinct from other functional effector lineages. We have therefore examined immature T cell precursors to determine when IL-2 inducibility is acquired in relation to other maturation events, such as expression of an Ag binding TCR, which is suspected to play an influential role in the determination of subclass commitment. In mature T cells, IL-2 is inducible via agonists of the phosphoinositide pathway, a network of signaling mediators shared by a wide variety of metazoan cell types. The universality of this activation pathway makes it seem less likely, a priori, to be a target of developmental change than the intrinsic susceptibility to induction of the IL-2 locus. However, our results presented here refute this expectation. In this report, we show that both TCR+ cells and pre-T cells too immature to express TCR can be induced to express IL-2 at high levels. The induction requirements for IL-2 expression, however, are different in TCR- and TCR+ cells. Even by using Ca2+ ionophore and phorbol ester to bypass the requirement for the TCR in cell activation, the TCR- cells also require the presence of the polypeptide hormone IL-1. By contrast, TCR+ mature cells not only can express IL-2 without IL-1, but also show no response to IL-1 when Ca2+ ionophore and phorbol ester are present. IL-1-dependent IL-2 producers appear in the thymus of repopulating radiation chimeras before "mature" (TCR+) T cells, whereas IL-1-independent IL-2 production is found only afterward. Thus, IL 2 inducibility per se apparently precedes TCR expression and all TCR-associated fate determination events. However, developmental alteration of signal transduction pathways may play a vital regulatory role in the later allocation of particular functional responses to appropriate lineages of T cells. PMID- 2106552 TI - Primary biliary cirrhosis. Inhibition of pyruvate dehydrogenase complex activity by autoantibodies specific for E1 alpha, a non-lipoic acid containing mitochondrial enzyme. AB - Antimitochondrial antibodies (AMA) are serologically characteristic of patients with PBC. Four Ag recognized by AMA have been recently identified, including protein X and the acyltransferases of three related multienzyme complexes: the pyruvate dehydrogenase complex (PDC), the branched-chain alpha-ketoacid dehydrogenase complex, and the alpha-ketoglutarate dehydrogenase complex. Each of these enzymes contains one or more lipoyl moieties as part of a major functional site. In addition, epitope mapping has suggested that the AMA target is this lipoic acid-binding region. In this report we demonstrate that sera from patients with PBC also recognize the E1 component (pyruvate dehydrogenase, EC 1.2.4.1) of PDC. PDC-E1 is composed of alpha and beta-chains. Reactivity with the 41 kD alpha chain was detected in 80 of 120 (66%) PBC sera by immunoblotting against purified PDC-E1; 2 of 120 sera also demonstrated reactivity with the 34 kD beta chain. In contrast, sera from patients with SLE, chronic active hepatitis, or progressive sclerosing cholangitis as well as sera from healthy volunteers did not react with PDC-E1. Furthermore, affinity-purified PBC sera against PDC-E1 alpha were able to inhibit PDC enzyme activity, whereas control sera could not. PDC-E1 alpha is now the fifth mitochondrial autoantigen of PBC to be identified. Similar to the four previously identified autoantigens, AMA appear to be directed to a functional site of PDC-E1 alpha inasmuch as they are able to inhibit enzyme function. However, PDC-E1 alpha is also unique in that it is the first identified mitochondrial autoantigen which does not contain lipoic acid. PMID- 2106553 TI - Direct evidence for an intracellular role for IFN-gamma. Microinjection of human IFN-gamma induces Ia expression on murine macrophages. AB - An intracellular action for IFN-gamma was detected by using microinjection technology. Human IFN-gamma (huIFN-gamma) does not ordinarily act on murine cells because it fails to bind to murine cell surface receptors. However, when huIFN gamma was microinjected into murine macrophages, a time and dose-dependent induction of Ia was detected by autoradiography on the surface of injected and neighboring cells. These results imply a direct role for internalized IFN-gamma and show that huIFN-gamma, although it fails to be recognized by murine cell surface receptors, can act internally on murine cells. The effect on Ia gene expression induced by microinjected huIFN-gamma was in part indirect: granulocyte/macrophage-CSF (GM-CSF) was released by IFN-gamma-injected macrophages, and this secondary mediator appeared to induce Ia on neighboring cells, inasmuch as anti-GM-CSF blocked Ia induction. Anti-GM-CSF also partially blocked Ia induction by extracellular murine IFN-gamma on murine macrophages. Thus, at least some of the Ia induction attributed to IFN-gamma was mediated by GM-CSF. PMID- 2106554 TI - Antigen-binding repertoire and Ig H chain gene usage among B cell hybridomas from normal and autoimmune mice. AB - LPS-stimulated B cells were used to generate a panel of mAb that were a random sample of the preimmune repertoire of C57BL/6 and highly autoimmune, viable motheaten mice. These mAb were tested for reactivity to a number of "self" and foreign Ag. Binding that could be detected only at nM mAb concentrations or less was considered significant. We found that a surprisingly high number of the mAb bound one or more of the Ag tested, and many mAb bound more than a single Ag. Ag induced mAb were likewise tested and found to have greatly reduced cross reactivities. We found no significant differences, either in frequency of Ag binding or degree of cross-reactivity, between normal and autoimmune mice. Furthermore, the frequency with which a given Ag was bound by our panel of mAb was found to be proportional to the size of the Ag. The frequency with which individual VH gene families were expressed by our panel was consistent with a stochastic usage of VH genes in the preimmune repertoire. We interpret these data as showing that the preimmune repertoire is highly cross-reactive and that the activation of autoreactive clones in autoimmune animals is due to a defect in cellular regulation rather than a difference in repertoire. PMID- 2106555 TI - The role of mast cell degranulation products in mast cell hyperplasia. I. Mechanism of action of nerve growth factor. AB - A variety of mast cell degranulating agents have previously been shown to induce mast cell hyperplasia in adult rats. In neonates 2.5 S nerve growth factor (NGF) induces a hyperplasia of both mucosal and connective tissue mast cells (MMC and CTMC). We have examined the role of the potent mast cell degranulating properties of NGF on its ability to induce mast cell hyperplasia. Administration of NGF in combination with the mast cell stabilizing agent disodium cromoglycate was found to abrogate the CTMC hyperplasia induced by NGF alone. Treatment of neonatal rats with the alternate degranulating agent compound 48/80 was found to induce a limited CTMC but not a MMC hyperplasia. A supernatant obtained by degranulating purified adult rat peritoneal mast cells with anti-IgE was found to induce hyperplasia of the CTMC population similar to that observed with NGF administration. However, this degranulation product supernatant only induced a limited MMC hyperplasia as judged by RMCP II content of the tissues. These results suggest that NGF has dual action inducing mast cell hyperplasia; CTMC hyperplasia being dependent on the ability of NGF to degranulate mast cells. MMC hyperplasia induced by NGF is independent of CTMC degranulation. Degranulation products from peritoneal mast cells act to increase both MMC and CTMC populations in the neonate. These data suggest that the CTMC population may be regulated by an autocrine positive feedback mechanism in vivo. PMID- 2106556 TI - Protective effect of recombinant tumor necrosis factor-alpha in murine salmonellosis. AB - The enhancement of resistance by i.p. administration of murine rTNF-alpha into mice against i.p. challenge with virulent Salmonella typhimurium was studied. Administration of TNF-alpha (5 x 10(4) U/mouse) into mice at 6 or 12 h before the challenge with S. typhimurium organisms enhanced the bactericidal capacity in the peritoneal cavities of the mice. The diminution of the infecting organism in the peritoneal cavities of the TNF-alpha-treated mice was not due to the systemic spread of the organism inasmuch as few organism were recovered from other areas such as the spleen and liver. The TNF-alpha treatment effected a slight increase of neutrophils in the peritoneal cavity, but did not effect an increase of macrophages, including Ia-bearing macrophages. The survival rate of mice infected with Salmonella was improved by the i.p. injection of TNF-alpha before infection. Co-administration of smaller doses of TNF-alpha (5 x 10(3) U) and murine rIFN gamma (10(2) U) at 6 h before the challenge also effectively enhanced bactericidal activity and protectivity. The cooperative effect of TNF-alpha and IFN-gamma was only seen when these recombinant cytokines were injected together at the proper time before the challenge. Injection of rabbit anti-TNF-alpha serum abolished the effects of TNF-alpha and the cooperative effect of TNF-alpha and IFN-gamma. Furthermore, the serum could abolish the cooperative effect of IFN gamma and LPS on bactericidal activity, suggesting participation of LPS-induced TNF-alpha in the cooperation. PMID- 2106557 TI - The effect of anti-IFN-gamma antibody on the protective effect of Lyt-2+ immune T cells against toxoplasmosis in mice. AB - The effect of an IFN-gamma mAb on the protective activity of immune T cells against Toxoplasma infection was examined in a murine model of toxoplasmosis. Mice that received anti-IFN-gamma antibody and immune spleen cells all died of toxoplasmosis after challenge with Toxoplasma tachyzoites. In contrast, mice that received normal IgG and immune spleen cells all survived the infection. The protective activity of Lyt-2+ immune T cells, previously shown to be the principal mediators of resistance against Toxoplasma in mice was completely ablated by the anti-IFN-gamma mAb. These results suggest that IFN-gamma is the major mediator of the resistance against Toxoplasma infection in mice which is conferred by immune T cells. PMID- 2106558 TI - Characterization of the molecular defects in the mouse E beta f and E beta q genes. Implications for the origin of MHC polymorphism. AB - The E beta f and E beta q genes have been isolated and sequenced to investigate the molecular basis for their defective expression. A previous study from this laboratory, which characterized the expression of these genes at the RNA level, showed both genes to have defects in posttranscriptional RNA processing. In this paper, the defect in the E beta q gene from the inbred mouse strain B10.G (Mus musculus domesticus) is shown to be a single base insertion in the RNA donor splice site of the first intron. This identical mutation was described previously for the E beta gene of the H-2w17 haplotype, which was derived from the Asian house mouse subspecies Mus musculus castaneus. Although it has been estimated that M. m. domesticus and M. m. castaneus separated from each other more than one million years ago, comparisons of genomic sequences reveal that the nonexpressed E beta q and E beta w17 alleles have not diverged significantly from one another; they are identical in their protein coding regions and have only minor differences elsewhere. In contrast, sequence comparisons of A beta q and A beta w17 show that these two expressed alleles differ by multiple amino acids. These findings provide evidence that selection, acting on expressed MHC proteins, plays a role in accumulation and maintenance of MHC polymorphism. The defective E beta f gene from the inbred strain B10.M has also been isolated. Sequence analysis has identified a mutation in the same RNA donor splice site as E beta q and E beta w17; however, in this gene the mutation is a single base substitution at position 5. PMID- 2106559 TI - Restricted utilization of germ-line VH genes and diversity of D regions in rabbit splenic Ig mRNA. AB - Previous studies have suggested that the majority of rabbit germ-line VH genes encode molecules that are rarely found in serum or secretory Ig. To examine the repertoire of expressed VH genes, we prepared a cDNA library from splenic mRNA of an alpha 1/alpha 1 rabbit and isolated 10 complete VH-encoding cDNA clones. None of the cDNA clones hybridized to an oligomer that had hybridized to more than 50% of cloned germ-line VH genes. These data indicate that only a subset of germ-line VH genes are used in functional VDJ rearrangements. DNA sequence analysis demonstrated that the 10 cDNA clones contained highly similar VH regions, further suggesting that the repertoire of utilized VH genes is limited. In contrast, the D regions of each of the 10 clones exhibited little similarity to one another, suggesting that the rabbit has a large D region repertoire. We propose that the apparent lack of diversity within the VH segment of VDJ rearrangements is offset by extensive D region diversity. PMID- 2106560 TI - The temporal order of appearance of transcripts from unrearranged and rearranged Ig genes in murine fetal liver. AB - The developmental time course of RNA transcribed from unrearranged (germ-line) and rearranged Ig genes in murine fetal liver was determined by a quantitative Northern blot analysis. Sterile Cmu transcripts and germ-line VH transcripts are detectable as early as day 14, whereas significant amounts of rearranged VDJCmu H chain transcripts do not appear until days 16 to 17. The sterile Cmu transcripts continuously increase in abundance throughout fetal development, in contrast to the germ-line VH transcripts, which decrease abruptly after day 16. Transcripts of germ-line and rearranged CK genes are detectable on day 17, and continue to increase in abundance on day 18. Transcripts from a pre-B cell specific gene, lambda 5, first appear on day 15, and reach maximum abundance on day 17. The order of these events is consistent with the known order of gene rearrangements and with the idea that transcriptional activation of germ-line loci is a prerequisite for Ig gene rearrangement. The lag between the onsets of germ-line Cmu and VH transcription and the appearance of VDJCmu transcripts suggests that additional developmentally regulated events may be necessary to achieve efficient expression of completely rearranged H chain genes. PMID- 2106561 TI - Arachidonic acid metabolism varies with the state of differentiation in density gradient-separated mouse epidermal cells. AB - Epidermal cells were isolated from adult inbred SENCAR (SSIN) mice and separated by density-gradient centrifugation. The cells were pooled into three fractions shown by previous work to differ in their state of differentiation and proliferative potential. The three fractions were examined for their capacity to metabolize exogenous 14C-arachidonic acid (AA) into prostaglandins (PG) and hydroxyeicosatetraenoic acids (HETE). Cells found in the upper two fractions, which are less dense, have less proliferative potential in vitro, and are more differentiated than cells in the lower more dense fraction, are much more active in producing PG from exogenous AA than are the more dense cells. This was observed in intact cells as well as cells disrupted by freeze-thawing following density separation. The same relationship was found for HETE production in that cytoplasmic preparations from the two fractions containing the less dense cells were much more active in the production of HETE than cytoplasmic preparations from the more dense fraction. The two upper fractions differed little from each other in the production of PG or HETE. These results indicate the presence of higher levels of active cyclooxygenase and lipoxygenases in fractions containing the less dense, more differentiated cells than in the fraction containing the more dense, less differentiated cells which are highly enriched for basal keratinocytes. PMID- 2106562 TI - Induction of epidermal hyperproliferation by topical n-3 polyunsaturated fatty acids on guinea pig skin linked to decreased levels of 13-hydroxyoctadecadienoic acid (13-hode). AB - Reversal of essential fatty acid deficiency (EFA) induced epidermal hyperproliferation was recently suggested to require linoleic acid and an active lipoxygenase product. Because the nature of this lipoxygenase product is unknown, we employed a model of n-3 polyunsaturated fatty acid (PUFA) induced hyperproliferation in guinea pig skin to test a possible reversal of the hyperproliferation by an oxidative metabolite of linoleic acid. Topical applications of two n-3 PUFA: 0.5% of eicosapentaenoic acid (20:5n-3) and/or of docosahexaenoic acid (22:6n-3) for 5 d induced severe epidermal hyperproliferation. Development of the epidermal hyperproliferation paralleled a marked decrease in the major epidermal linoleic acid lipoxygenase product (13 hydroxyoctadecadienoic acid; 13-HODE). The application of 0.1% of 13-HODE to the n-3 PUFA-induced guinea pig hyperproliferative skin resulted in the restoration of normal epidermal histology and reversal of hyperproliferation as determined by epidermal uptake of 3H-thymidine. These data support the view that 13-HODE may represent the endogenous cutaneous mediator necessary for full restoration of cutaneous symptoms of essential fatty acid deficiency. Furthermore, the topical use of n-3 PUFA for the disruption of normal metabolism of skin n-6 EFA (linoleic acid) does serve as a useful tool for further investigations into the regulatory mechanisms of in vivo epidermal proliferation/differentiation. PMID- 2106563 TI - Interferons exhibit temporally distinct regulation of two bovine macrophage Fc receptors. AB - Interferon (IFN)-induced modulation of two distinct types of Fc receptors (FcR) on bovine bone marrow culture-derived macrophages was quantified by flow cytometry. We have established the presence of separate FcR for monomeric and aggregated IgG on these cells, equivalent to the FcRI and FcRII of mice, respectively. These two kinds of FcR differed in protease sensitivity, hierarchy of preferential binding of immunoglobulin sub-class, and cross-inhibition. Treatment of macrophages with either recombinant bovine IFN-gamma (rBoIFN gamma) or rBoIFN alpha I1 produced a dose-dependent increase in the expression of both types of FcR; however, expression of the FcR for aggregated IgG was increased a full 24 h prior to that for monomeric antibody. Further, expression of the FcRII equivalent declined substantially by 48 h of IFN exposure, while the presence of the FcRI-equivalent receptor was still enhanced. Finally, low doses (1 unit/ml) of either rBoIFN gamma or rBoIFN alpha I1 failed to alter FcR expression, yet mixtures of IFNs at this concentration were able to potentiate FcR expression. This is the first time that a differential time course of induction of FcR types by IFNs and the effects of mixtures of IFNs on FcR expression has been described in any species. PMID- 2106564 TI - A rapid cold-hardening response protecting against cold shock injury in Drosophila melanogaster. AB - In studies of insect cold-hardiness, the supercooling point (SCP) is defined as the temperature at which spontaneous nucleation of body fluids occurs. Despite having an SCP of -20 degrees C, adults of Drosophila melanogaster did not survive exposure to -5 degrees C, which suggests that cold shock causes lethal injury that is not associated with freezing. If, however, flies were chilled at 5 degrees C, for as little as 30 min, approximately 50% of the flies survived exposure to -5 degrees C for 2h. This capacity to cold-harden rapidly was greatest in 3- and 5-day-old adults. The rapid cold-hardening response was also observed in larvae and pupae: no larvae survived 2 h of exposure to -5 degrees C, whereas 63% pupariated if chilled at 5 degrees C before subzero exposure. Similarly, although exposure of pupae to -8 degrees C was lethal, if pre-chilled at 5 degrees C 22% eclosed. This extremely rapid cold-hardening response may function to allow insects to enhance cold-tolerance in response to diurnal or unexpected seasonal decreases in environmental temperature. PMID- 2106565 TI - Compensation of progressive hypercapnia in the toad (Bufo marinus) and the bullfrog (Rana catesbeiana). AB - Toads (Bufo marinus L.) and bullfrogs (Rana catesbeiana Shaw) were subjected to a series of 24 h step increases in aerial CO2 (2, 4, 6 and 8%) to assess the degree of extracellular pH compensation at each CO2 level and to ascertain the importance of cutaneous ion transport in this process. Elevation of plasma [HCO3 ] occurs during the 24 h period, with the bullfrogs showing a greater ability to compensate at each step. There was no indication that a [HCO3-] threshold of 30 mmol l-1 existed in either species, although bullfrogs appeared to have a greater compensatory potential when exposed to the higher levels of CO2. The results of the ion flux experiments suggest that neither the terrestrial Bufo nor the semi aquatic Rana use their skin to any great extent for acid-base balance during hypercapnia. PMID- 2106566 TI - Interleukin 2 (IL-2)-induced tyrosine phosphorylation of IL-2 receptor p75. AB - We have recently established a mAb named TU11 mAb specific for the p75 subunit of human IL-2 receptor (IL-2R). The present study using TU11 mAb demonstrates the IL 2-induced phosphorylation of IL-2Rp75 on tyrosine residues in IL-2-dependent T cells. The tyrosine phosphorylation is mediated by the high affinity IL-2R, correlates with the IL-2-induced cell growth, and rapidly increases during the first 5 min of IL-2 stimulation. Phosphorylation of serine and threonine residues of IL-2Rp75 is also detected, but its IL-2 dependency is not significant during at least the first 5 min. These results suggest some roles of a tyrosine kinase associated with IL-2Rp75 in the IL-2-induced signal-transducing pathway. PMID- 2106567 TI - Incorporation, distribution, and turnover of arachidonic acid within membrane phospholipids of B220+ T cells from autoimmune-prone MRL-lpr/lpr mice. AB - The metabolism of AA-containing phosphoglycerides within T cell membranes leads to the generation of second messengers that appear to play a crucial role in transmembrane signal transduction. To test the hypothesis that aberrations in the movement of arachidonoyl-phospholipids are associated with and may potentially contribute to abnormal T cell function, the incorporation, distribution, and turnover of AA within the membrane glycerolipids of cells that are known to exhibit immunoregulatory disturbances was examined. Thy-1+, Ly-1+, L3T4-, Lyt-2-, B220+ T cells from autoimmune MRL-lpr/lpr mice were used as the cellular model. In contrast to control lymph node T cells, which preferentially incorporate labeled AA into phosphatidylcholine (PC), B220+ T cells displayed a predilection for distributing [3H]arachidonate into phosphatidylinositol (PI). The arachidonoyl-phospholipid pools were normal in B220+ T cells. The constitutive turnover of [3H]arachidonoyl-PI was significantly enhanced and that of [3H]arachidonate-PC substantially reduced in B220+ T cell compared with control cells. Using membrane homogenates B220+ T cells demonstrated a functional increase in the levels of lyso-PI. Intact B220+ T cells prelabeled with [3H]myoinositol and cultured in the absence of stimulation with exogenous antigens or mitogens, exhibited increased production of lyso-PI. The data indicate that the preferential formation of [3H]arachidonoyl-PI in B220+ T cells is the result of greatly increased, constitutive PI turnover that appears to be due to a membrane phospholipase A2 activity. It remains possible that disturbances in the movement of arachidonate within phospholipids of B220+ T cells play a role in the expression of aberrant immunological activity. PMID- 2106568 TI - The sequence of the mu transmembrane segment determines the tissue specificity of the transport of immunoglobulin M to the cell surface. AB - Membrane IgM is expressed on the surface of B lymphocytes. It is not transported to the surface of transfected plasmacytoma or COS cells. Here, we show that mutation of four hydrophilic amino acids in the microm transmembrane is sufficient to overcome the intracellular retention of membrane IgM in non-B cells. This suggests that the B cell-specific IgM-associated proteins that have been postulated to assist the transport of membrane IgM to the cell surface (3) act either by forming a hydrophobic sheath that surrounds the microm transmembrane segment or by displacing an interaction with this segment that would otherwise cause retention. Experiments with a CD8/mu hybrid H chain indicate that the proteins that assist the transport of membrane IgM to the B cell surface at most need the mu CH4 and transmembrane/cytoplasmic portion for interaction. PMID- 2106569 TI - DNA rearrangement and constitutive expression of the interleukin 6 gene in a mouse plasmacytoma. AB - To study the potential involvement of IL-6 in the development of plasmacytomas, a number of plasmacytoma lines were analyzed for alterations in the IL-6 locus. A DNA rearrangement due to the insertion of an intracisternal A particle retrotransposon 18 bp 5' of the transcriptional start site was detected in the cell line MPC11. The IL-6 gene is constitutively expressed in MPC11, suggesting the involvement of IL-6 in the development of certain myeloma/plasmacytomas according to the "autocrine growth hypothesis". PMID- 2106570 TI - Pentachlorophenol-associated aplastic anemia, red cell aplasia, leukemia and other blood disorders. AB - Aplastic anemia, pure red cell aplasia, leukemia, lymphoma and other hematologic disorders have followed exposure to products containing the pesticide pentachlorophenol (PCP). Information in a 25-year compilation of documented case reports is summarized, involving industrial and home exposure and accidental poisoning in a nursery. The potential hematologic, mutagenic and carcinogenic effects of PCP and its dioxin-dibenzofuran contaminants also are reviewed. Owing to widespread contamination of the environment by PCP products, and latent periods of up to several decades after exposure before these disorders become manifest clinically, it is necessary to consider their etiologic or contributory role. These issues continue to surface in toxic tort litigation relative to causation. PMID- 2106572 TI - Studies on the pathogenicity of a nairovirus, Dugbe virus, in normal and immunosuppressed mice. AB - Susceptibility to lethal infection with the KT281/75 strain of the tick-borne nairovirus, Dugbe virus, was similar in an outbred strain and several inbred strains of mice. For the outbred strain, both neural and extraneural routes of virus inoculation resulted in lethal infection, but susceptibility decreased with age and only intracerebral inoculation produced a lethal infection in adults. In newborn mice, subcutaneous (s.c.) inoculation of virus (analogous to a tick-bite) produced a disseminated infection, titres being highest in the upper respiratory tract (URT), spleen and liver at 5 days post-inoculation (p.i.), the heart at 7 days p.i. and brain by 8 days p.i. In neonates inoculated intranasally (i.n.), by contrast, virus spread rapidly from the URT to the brain by 2 days p.i., in the absence of a detectable viraemia. Virus was undetectable in the blood of s.c. and i.n. inoculated adults; in the former, virus replication was limited to the site of inoculation, and in the latter virus grew in the respiratory tract and again spread to the brain. Immunosuppression of i.n. inoculated adult mice with cyclophosphamide produced some mortality indicating that host defences are important in protecting the adult, especially as newborn and adult lung tissue were equally able to support the growth of Dugbe virus in culture. The similarity between the pattern of Dugbe virus infection in the mouse and that of other, more pathogenic nairoviruses suggests that, although haemorrhagic disease was not observed, this may be a useful model for studying the genetic basis of nairovirus virulence and for testing vaccines and anti-viral drugs. PMID- 2106571 TI - G protein control of potassium channel activity in a mast cell line. AB - Using the patch-clamp technique, we studied regulation of potassium channels by G protein activators in the histamine-secreting rat basophilic leukemia (RBL-2H3) cell line. These cells normally express inward rectifier K+ channels, with a macroscopic whole-cell conductance in normal Ringer ranging from 1 to 16 nS/cell. This conductance is stabilized by including ATP or GTP in the pipette solution. Intracellular dialysis with any of three different activators of G proteins (GTP gamma S, GppNHp, or AlF-4) completely inhibited the inward rectifier K+ conductance with a half-time for decline averaging approximately 300 s after "break-in" to achieve whole-cell recording. In addition, with a half-time averaging approximately 200 s, G protein activators induced the appearance of a novel time-independent outwardly rectifying K+ conductance, which reached a maximum of 1-14 nS. The induced K+ channels are distinct from inward rectifier channels, having a smaller single-channel conductance of approximately 8 pS in symmetrical 160 mM K+, and being more sensitive to block by quinidine, but less sensitive to block by Ba2+. The induced K+ channels were also highly permeable to Rb+ but not to Na+ or Cs+. The current was not activated by the second messengers Ca2+, inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, or by cyclic AMP-dependent phosphorylation. Pretreatment of cells with pertussis toxin (0.1 microgram/ml for 12-13 h) prevented this current's induction both by guanine nucleotides and aluminum fluoride, but had no effect on the decrease in inward rectifier conductance. Since GTP gamma S is known to stimulate secretion from patch-clamped rat peritoneal mast cells, it is conceivable that K+ channels become inserted into the plasma membrane from secretory granules. However, total membrane capacitance remained nearly constant during appearance of the K+ channels, suggesting that secretion induced by GTP gamma S was minimal. Furthermore, pertussis toxin had no effect on secretion triggered by antigen, and triggering of secretion before electrical recording failed to induce the outward K+ current. Finally, GTP gamma S activated the K+ channel in excised inside-out patches of membrane. We conclude that two different GTP-binding proteins differentially regulate two subsets of K+ channels, causing the inward rectifier to close and a novel K+ channel to open when activated. PMID- 2106573 TI - Vacuolization, incubation period and survival time analyses in three mouse genotypes injected stereotactically in three brain regions with the 22L scrapie strain. AB - In previous studies we showed that C57BL mice injected stereotactically in the cerebellum with the 22L scrapie strain had a significantly shorter incubation period than those injected with the same agent in other brain regions. In mice injected in the cerebellum, vacuolization was limited to the cerebellum, medulla and mesencephalon, whereas injection into forebrain regions resulted in vacuolization in all brain regions. The studies suggested that the cerebellum had a selective vulnerability for 22L. In this study we examined the interaction between host genotype and selective vulnerability of specific brain regions. The mouse gene that has the most profound effect on pathogenesis, particularly incubation period, is termed Sinc (scrapie incubation). Groups of mice with three genotypes of Sinc (s7s7, p7p7 and their F1 cross, s7p7) were injected with 22L into the cerebral cortex, thalamus or cerebellum. Analysis of incubation periods showed that, regardless of the host genotype, the cerebellum injection group had a significantly shorter incubation period than groups injected in other regions. After cerebellum injection vacuolization was limited to the cerebellum, medulla and mesencephalon in all three host genotypes. The location of vacuoles within the cerebellum differed depending upon the host strain. Vacuolization developed almost exclusively in grey matter in s7s7 mice, mainly in white matter in p7p7 mice, and in both grey and white matter in F1 mice. These results demonstrate that the selective vulnerability of the cerebellum to induction of clinical disease by 22L does not depend on host genotype, but host genotype does affect lesion distribution within the cerebellum. PMID- 2106574 TI - Pathogenesis and pathology of scrapie after stereotactic injection of strain 22L in intact and bisected cerebella. AB - The mechanisms involved in the spread of scrapie within the brain remain unclear. To examine this issue the 22L scrapie strain was injected in one side of the cerebellum of mice in which the cerebellum had been bisected prior to injection. Another group of animals received the same injection into intact cerebella, i.e. without prior bisection. We found that bisection of the cerebella delayed the spread of scrapie agent from the injection site to the contralateral side of the cerebellum and that the occurrence of vacuolization was not as extensive and was markedly delayed in the uninjected side compared to its occurrence after injection in the intact cerebellum. Replication of agent in an area preceded the development of vacuolization in that area by several weeks. There was marked loss of Purkinje cells on the injected side of bisected cerebella, with no loss seen on the uninjected side. The incubation period of scrapie disease in mice injected after cerebellar bisection was significantly longer than after the injection of intact cerebella. The results in this study suggest that the scrapie agent spreads along intact nerve cell tracts, probably by axonal transport. PMID- 2106575 TI - Effect of tumor necrosis factor on the human fibrinolytic system. AB - We report the effects on the fibrinolytic system of intravenous (IV) recombinant tumor necrosis factor-alpha (rTNF-alpha) infusions in patients with advanced cancers. During a phase I clinical trial of rTNF-alpha, the plasma fibrinolytic system was closely monitored, measuring tissue-type plasminogen activator (tPA) antigen, plasminogen activator (PA) inhibitor activity, and plasma fibrinolytic activity. Thirteen patients with refractory malignancies received 40, 80, or 160 micrograms/m2 rTNF-alpha as 2-hour IV infusions. After a 1-week rest, the same dose was repeated daily for 5 days every 3 weeks for a maximum of four courses. The serum rTNF-alpha levels peaked at the completion of the IV infusion and rapidly declined thereafter, becoming unmeasurable within 1 hour in all patients. rTNF-alpha infusion markedly alters the plasma fibrinolytic system. During the 2 hour infusion, significant increases in the tPA antigen and plasma fibrinolytic activity were seen. After the infusion, PA inhibitor activity increased, neutralizing the plasma fibrinolytic activity. The increase in PA inhibitor activity was maximal 6 hours after the onset of the rTNF-alpha infusion. Fibrinolytic properties returned to pretreatment values within 24 hours. Daily rTNF-alpha infusions caused changes in plasma tPA antigen and PA inhibitor similar to those of single infusions. We conclude from these observations that the administration of rTNF-alpha in vivo to cancer patients causes profound alterations of endothelial cell-derived components of the fibrinolytic system. PMID- 2106577 TI - Indium-111-labeled leukocyte scintigraphy in hemodialysis access-site infection. AB - Bacterial sepsis, a significant complication of chronic hemodialysis, is generally the result of infection at the vascular access site. We retrospectively reviewed the utility of indium-111-(111In) labeled autologous leukocyte scintigraphy in 26 patients (30 scans) with synthetic vascular grafts, on chronic hemodialysis, in whom hemodialysis access site infection was a diagnostic consideration. Leukocyte scintigraphy correctly identified all fifteen access site infections; there was one false-positive study, for an overall sensitivity and specificity of 100% and 93%, respectively. Of particular significance is the fact that in nine (60%) of the fifteen access-site infections, physical examination was normal. Our data indicate that 111In-labeled leukocyte scintigraphy is a useful procedure for the diagnosis of hemodialysis access-site infection, and it is especially valuable when physical examination of the access site is normal. PMID- 2106576 TI - Comparison of technetium-99m-HM-PAO leukocytes with indium-111-oxine leukocytes for localizing intraabdominal sepsis. AB - Technetium-99m-HM-PAO [( 99mTc]HM-PAO) leukocyte and indium-111-oxine (111In oxine) leukocyte scanning were carried out simultaneously in 41 patients at 4 hr and 24 hr after reinjection to determine whether the 4-hr 99mTc scan could replace the 24-hr 111In scan for detecting intraabdominal sepsis. Abdominal infection was confirmed in 12 cases. The 4-hr 99Tc-leukocyte scan, the 4-hr 111In leukocyte scan, and the 24-hr 111In-leukocyte scan yielded a sensitivity of 100%, 67%, and 100%, respectively, and a specificity of 62%, 90%, and 86%, respectively. The 24-hr 99mTc-leukocyte scan also produced a sensitivity of 100%, but it was falsely positive in all 29 cases without infection due to physiologic bowel uptake. False-positive 4-hr 99mTc-leukocyte scans were also produced by physiologic bowel uptake in seven cases all of whom had true-negative 4-hr and 24 hr 111In-leukocyte scans. Because of the high incidence of false-positive 4-hr [99mTc]HM-PAO leukocyte scans, it was concluded that they could not replace 24-hr 111In-leukocyte scans for detecting intraabdominal sepsis, and that serial 99mTc leukocyte scans starting earlier than 4 hr after reinjection must be evaluated. PMID- 2106578 TI - Effects of iron deficiency on lead excretion in children with moderate lead intoxication. AB - The effect of iron status on calcium disodium edetate (CaNa2EDTA)-induced lead diuresis was examined in 112 children with moderate lead intoxication. Patients whose blood lead levels were between 25 and 55 micrograms/dl and who had erythrocyte protoporphyrin concentrations greater than or equal to 35 micrograms/dl underwent provocative testing to determine the need for a full course of chelation therapy. A blood sample for lead, erythrocyte protoporphyrin, and serum ferritin determinations was obtained immediately before the intramuscular administration of CaNa2EDTA, 500 mg/m2. Determination of urinary lead level was based on an 8-hour urine collection. Blood lead and ferritin levels were significantly correlated with urinary lead excretion: r = 0.542 and 0.298, respectively, p less than 0.01 for both. Multiple regression models were tested to assess the independent effects of the variables. With blood lead level controlled, ferritin remained significantly associated with urinary lead excretion; for every 1 ng/ml increase in ferritin, urinary lead increased by 2.4 micrograms. This small effect of ferritin on urinary lead was illustrated in a discriminant analysis. Using blood lead level by itself as the independent variable resulted in a 76% correct assignment of provocative test outcomes. Knowing the ferritin level improved this assignment accuracy by only 3%. We conclude that the iron status, as measured by serum ferritin, of children with moderate lead intoxication, has a small but significant effect on CaNa2EDTA induced lead diuresis. This effect may influence the interpretation of borderline provocative test outcomes. Although chelation therapy should not be withheld pending treatment of iron deficiency, lead stores should be reassessed after iron repletion. PMID- 2106579 TI - Serial incontinence assessment in elderly inpatient men. AB - Urinary incontinence is a major problem for elderly chronic care patients. As a consequence, a high level of nursing care is required for patient management. Because incontinence rehabilitation programs are usually implemented during the day shift, the incidence of incontinence according to time of day has major implications regarding patient management. Although treatment is usually based on severity, assessment of incontinence severity in elderly chronic care inpatients is difficult. In this study, a telemetric incontinence detection system was developed to identify incontinence episodes. An absorbent pad exchange technique was used for incontinence volume measurement. The study group, 66 chronic care inpatient men over 65 years old, were subject to incontinence measurements over 10 days during all nursing shifts using the telemetric incontinence detection system. The results showed a significantly high incidence of incontinence episodes during the evening nursing shift. The volume of involuntary urine loss was significantly higher during the night nursing shift. Thus, the highest level of incontinence severity occurred during the time of day when nursing staff on chronic care units is usually the lowest. PMID- 2106580 TI - The dimensional stability of elastomeric impression materials following disinfection. AB - Public awareness of infectious diseases has focused attention on the prevention of nosocomial disease. Difficulties in sterilizing impressions have led to chemical disinfection as an alternative. Recent literature indicated a lack of consensus between researchers about distortion caused by disinfection. A polysulfide, polyether, and vinyl polysiloxane were disinfected by immersion in iodophor, sodium hypochlorite, and glutaraldehyde. Distortion was evaluated by use of a stainless steel die (ADA specification No. 19). Linear dimension variations after disinfection were clinically insignificant. PMID- 2106581 TI - Acid-stable 2'-fluoro purine dideoxynucleosides as active agents against HIV. AB - 2',3'-Dideoxy purine nucleosides have anti-HIV activity in vitro and the inosine analogue is being clinically evaluated. The instability of these compounds toward acidic conditions complicates oral administration. The effect of the addition of a fluorine atom to the 2'-position was investigated by preparing the fluorine containing 2'-erythro and 2'-threo isomers of ddA and the threo isomer of ddI. All fluorine-containing compounds were indefinitely stable to acidic conditions which completely decomposed ddI (1) and ddA (2) in minutes. While the fluorine containing erythro isomer, 5, was inactive, the threo isomers, 2'-F-dd-ara-A (3) and 2'-F-dd-ara-I (4), were just as potent and active in protecting CD4+ ATH8 cells from the cytopathogenic effects of HIV-1 as the parent drugs. Exposure to pH 1 at 37 degrees C prior to testing destroyed the activity of ddA and ddI but left the anti-HIV properties of 3 and 4 unchanged. The fluorinated analogues also protected cells exposed to HIV-2 and inhibited gag gene product expression but not as effectively as the parent compounds. The fluorine-containing analogues appear to be somewhat more toxic in vitro to the antigen- and mitogen-driven proliferation of immunocompetent cells than their corresponding parent compounds. PMID- 2106582 TI - Linkage of internal minisatellite loci on chromosome 1 and exclusion of autosomal dominant retinitis pigmentosa proximal to rhesus. AB - We report the exclusion of a locus for autosomal dominant retinitis pigmentosa proximal to the rhesus locus in a single large pedigree. In addition, a previously unreported linkage is described between two chromosome 1 markers, which confirms that a highly variable minisatellite locus is placed internally on chromosome 1. PMID- 2106583 TI - In vitro secondary structure analysis of mRNA from lacZ translation initiation mutants. AB - mRNA secondary structure can be an important determinant of the efficiency of translation initiation. To study the effect of secondary structure on translation initiation, in vitro secondary structure analysis was performed on 32 lacZ RNA transcripts that differ in their in vivo translation initiation efficiencies because of mutations. We have shown that well-translated RNA has a relatively unstructured translation initiation region in vitro. In contrast, the translation initiation region of many of the poorly translated RNA transcripts is involved in a stem-loop structure. Mutations that decrease the in vitro stability of the stem loop increase the frequency of translation initiation. The sequences responsible for forming this stem-loop structure were localized to a small region of RNA. The results confirm some of the previous predictions of the RNA secondary structure of the mutant RNAs based on computer modeling, but they disagree with some of the predicted long-range interactions. PMID- 2106584 TI - Chromatin superstructure-dependent crosslinking with DNA of the histone H5 residues Thr1, His25 and His62. AB - The points of histone H5 interactions with DNA within nucleosomes and chromatin at different levels of compaction are delineated by identification of H5 amino acid residues that can be covalently bound to DNA. Three major crosslinkable points of H5 are His25, His62 (both within the globular part of the molecule), and N-terminal Thr1. His25 interacts with the terminal regions of nucleosomal DNA; His62 appears to bind more distal segments of the linker DNA. The His25-DNA crosslink predominates in the isolated mononucleosomes and persists throughout the chromatin condensation states studied, from extended oligonucleosomal chains to nuclei. His62 is the strongest crosslinking site in nuclei; in oligonucleosomes, the predominance of the His62-DNA crosslink requires the number of nucleosomes in the chain to be above some critical value. The Thr1-DNA crosslink is generated only in decondensed poly- or oligonucleosomes, but not in mononucleosomes. Thus, underlying the higher-order folding transitions of the nucleosomal chain is the restructuring of H5-DNA interactions. PMID- 2106585 TI - Refined three-dimensional structure of phycoerythrocyanin from the cyanobacterium Mastigocladus laminosus at 2.7 A. AB - The structure of the phycobiliprotein phycoerythrocyanin from the thermophilic cyanobacterium Mastigocladus laminosus has been determined at 2.7 A resolution by X-ray diffraction methods on the basis of the molecular model of C-phycocyanin from the same organism. Hexagonal phycoerythrocyanin crystals of space group P6(3) with cell constants a = b = 156.86 A, c = 40.39 A, alpha = beta = 90 degrees, gamma = 120 degrees are almost isomorphous to C-phycocyanin crystals. The crystal structure has been refined by energy-restrained crystallographic refinement and model building. The conventional crystallographic R-factor of the final model was 19.2% with data to 2.7 A resolution. In phycoerythrocyanin, the three (alpha beta)-subunits are arranged around a 3-fold symmetry axis, as in C phycocyanin. The two structures are very similar. After superposition, the 162 C alpha atoms of the alpha-subunit have a mean difference of 0.71 A and the 171 C alpha atoms of the beta-subunit differ by 0.51 A. The stereochemistry of the chiral atoms in the phycobiliviolin chromophore A84 is C(31)-R, C(4)-S. The configuration of the chromophore is C(10)-Z, C(15)-Z and the conformation C(5) anti, C(9)-syn and C(14)-anti like the phycocyanobilin chromophores in phycoerythrocyanin and C-phycocyanin. PMID- 2106586 TI - Refined crystal structure of the phosphorylase-heptulose 2-phosphate oligosaccharide-AMP complex. AB - The crystal structure of phosphorylase b-heptulose 2-phosphate complex with oligosaccharide and AMP bound has been refined by molecular dynamics and crystallographic least-squares with the program XPLOR. Shifts in atomic positions of up to 4 A from the native enzyme structure were correctly determined by the program without manual intervention. The final crystallographic R value for data between 8 and 2.86 A resolution is 0.201, and the overall root-mean-square difference between the native and complexed structure is 0.58 A for all protein atoms. The results confirm the previous observation that there is a direct hydrogen bond between the phosphate of heptulose 2-phosphate and the pyridoxal phosphate 5'-phosphate group. The close proximity of the two phosphates is stabilized by an arginine residue, Arg569, which shifts from a site buried in the protein to a position where it can make contact with the product phosphate. There is a mutual interchange in position between the arginine and an acidic group, Asp283. These movements represent the first stage of the allosteric response which converts the catalytic site from a low to a high-affinity binding site. Communication of these changes to other sites is prevented in the crystal by the lattice forces, which also form the subunit interface. The constellation of groups in the phosphorylase transition state analogue complex provides a structural basis for understanding the catalytic mechanism in which the cofactor pyridoxal phosphate 5'-phosphate group functions as a general acid to promote attack by the substrate phosphate on the glycosidic bond when the reaction proceeds in the direction of glycogen degradation. In the direction of glycogen synthesis, stereoelectronic effects contribute to the cleavage of the C-1-O-1 bond. In both reactions the substrate phosphate plays a key role in transition state stabilization. The details of the oligosaccharide, maltoheptaose, interactions with the enzyme at the glycogen storage site are also described. PMID- 2106587 TI - Hemorrhagic pheochromocytoma in a pregnant patient with neurofibromatosis. Sonographic appearance. PMID- 2106588 TI - Bladder neurofibromatosis in childhood. Noninvasive imaging. PMID- 2106589 TI - Are clinical trials cost-effective? PMID- 2106590 TI - Anticoagulation for noncardiac procedures in patients with prosthetic heart valves. Does low risk mean high cost? AB - Hospitalizations for patients with prosthetic heart valves undergoing noncardiac surgery are frequently prolonged for intravenous heparin therapy to decrease the incidence of thromboembolism while patients are not taking oral anticoagulant agents. Because the rate of thromboembolic events is quite low and the period of increased risk is very short, the cost of preventing these rare events can be great. We performed cost-effectiveness analyses addressing these issues. We calculated the marginal cost per additional quality-adjusted year of life gained per thromboembolic event averted and per death averted. We conclude that the marginal cost of prolonging hospitalization to administer heparin is prohibitively high compared with most contemporary therapies, except when the patient has the most thrombogenic of valves. We also discuss the ethical and legal ramifications of integrating the results of cost-effectiveness analyses into clinical practice. PMID- 2106591 TI - Update on chronic granulomatous diseases of childhood. Immunotherapy and potential for gene therapy. PMID- 2106592 TI - Understanding the recent growth in Medicare physician expenditures. AB - This study employs several large Health Care Financing Administration data sets for 1983 and 1985 to examine the recent growth in Medicare physician services. The study concludes that the recent growth (approximately 15% in real terms between 1983 and 1985) has been more rapid in areas with higher incomes per capita and suggests that this may be related to faster adoption and diffusion of new medical technologies in these areas. The volume of physician services had grown considerably faster for those specialists who utilize newer procedures and technologies than for those who do not. The study also provides evidence that the sharp increase in assignment rates in recent years because of the introduction of the physician participation program also contributed to the growth in physician services during this period. Medicare's prospective payment system, which controlled hospital payments and encouraged hospitals to become more efficient, had at most a small positive impact on the growth in Part B spending. Finally, the freeze on physician's fees did not seem to have had a major impact on the volume of physician services. PMID- 2106593 TI - ASPEN. American Society for Parenteral and Enteral Nutrition. 14th clinical congress program. January 28-31, 1990, San Antonio, TX. Abstracts. PMID- 2106595 TI - [Qualitative analysis of tissue plasminogen activator in plasma obtained from various liver diseases by gel filtration and affinity chromatography]. AB - Tissue plasminogen activator (t-PA) in plasma obtained from patients with acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, drug induced intrahepatic cholestasis, obstructive jaundice, fulminant hepatitis or disseminated intravascular coagulation (DIC), was analysed chromatographically. Liver disease cases showed a new peak (peak C) on HPLC fractionation. The protein of peak C had a lower molecular weight than ovalbumin. Lysine- and zinc- chelating affinity chromatography revealed that the peak C consist with the light chain (L-chain) of t-PA. The L-chain was also found in patients with DIC, but disappeared after improvement of DIC. Therefore, it was suggested that appearance of the L-chain would be related to acceleration of secondary fibrinolysis in plasma. The L-chain was especially high in plasma obtained from patients with decompensated liver cirrhosis. These results indicated that high increase of the L-chain in cases of severe liver disease may be due to either impaired clearance of t-PA in the liver or secondary hyperfibrinolysis accompanied by DIC. We concluded that determination of the L-chain of t-PA may contribute to clarify the mechanism of hyperfibrinolysis in liver diseases. PMID- 2106594 TI - [Two cases of tubular adenoma of the breast]. AB - Two rare cases of a tubular adenoma of the breast are reported, together with a clinicopathological review of the pertinent literature. Only 14 cases of this histological type have so far been reported in Japan. Both patients were single women aged 22 and 34 years, respectively. In case 1, a mass was found in the axilla, and in case 2, a breast cancer was simultaneously found in the contralateral breast. In each patient, a mass that measured 2 cm in diameter was oval, elastic and firm and smooth on the surface. In each instance the result of the biopsy performed led to a diagnosis of a fibroadenoma. Microscopically, the tumor was sharply demarcated from the adjacent breast tissue and consisted of homogeneous epithelial cells with small tubular structures and a minimal stromal component. PMID- 2106596 TI - Studies on antiplatelet effect of OP-41483, a prostaglandin I2 analog, in experimental animals. I. Effect on platelet function and thrombosis. AB - Antiplatelet and antithrombotic effects of OP-41483, a PGl2 analog, were studied in experimental animals, and the following results were obtained: 1) With 10 min intravenous infusion to guinea pigs, OP-41483 inhibited platelet adhesiveness and platelet aggregation at 300-1000 ng/kg/min and 1000 ng/kg/min, respectively. In these effects, OP-41483 was 1-3 times more potent than carbacyclin and 3 times less potent than PGl2. 2) With oral administration to guinea pigs, OP-41483 given as its alpha-cyclodextrin clathrate (OP-41483 alpha-CD) inhibited platelet adhesiveness at doses higher than 1.0 mg/kg (expressed in terms of OP-41483), whereas PGl2 and carbacyclin did not at 10 mg/kg. OP-41483 alpha-CD also inhibited platelet aggregation after a single dose of 3 mg/kg and repeated doses of 3 mg/kg/day for 7 days. 3) In the electrically induced thrombosis model of guinea pig mesenteric artery, OP-41483 (300-1000 ng/kg/min, i.v.-infusion) and OP 41483 alpha-CD (1.0-3.0 mg/kg, p.o.) inhibited thrombus formation, but heparin (1.0-10 U/kg/min, i.v.-infusion) did not. 4) In the rabbit extracorporeal circulation thrombosis model, OP-41483 (100 and 300 ng/kg/min, i.v.-infusion) inhibited thrombus formation in the extracorporeal shunt and prevented the decrease in platelet count, hematocrit and fibrinogen level in circulating blood. Heparin (1.0-3.0 U/kg/min, i.v.-infusion) also inhibited the thrombus formation and the decrease in fibrinogen level, but did not inhibit the decrease in hematocrit and platelet count. PMID- 2106597 TI - [Report of five cases of major surgery during anticoagulant therapy after prosthetic valve replacement]. AB - The major surgery for gastroduodenal ulcer, gastric cancer, esophageal cancer, and mediastinal tumor, were performed on 5 patients during anticoagulant therapy after prosthetic valve replacement. In the postoperative management, Dipyridamole (30 mg/day) was given in case 1, Heparin sodium (24,000 mu/day) in case 2, 3, and Gabexate Mesilate in case 4, 5. Postoperative course was uneventful in case 1, 3, 4, 5, intratracheal bleeding was recognized on the 3rd postoperative day and treated by reducing of heparin dose in case 2. Gabexate Mesilate was thought to be effective and free from complication in case 4, 5. PMID- 2106598 TI - Morbidity of patients with analgesic-associated nephropathy on regular dialysis treatment and after renal transplantation. AB - In a retrospective study, patients with end-stage renal failure from analgesic associated nephropathy - 55 on regular dialysis treatment and 12 after renal transplantation - were under observation for 57 and 33 months, respectively. Of these 34 patients on chronic hemodialysis had suffered from different cardiovascular diseases. Hypertriglyceridemia was diagnosed in 62% of the patients, arterial hypertension requiring antihypertensive therapy in 44%. In three patients (5%) carcinoma of the urinary bladder were diagnosed. The leading causes of death in 21 patients included cardiovascular diseases (29%), hyperkalemia (19%), sepsis, and malignant tumors (14% each). Rejection occurred in 3 out of 12 patients after renal transplantation. Again, cardiovascular morbidity was high (58%) with coronary heart disease being present in 33% of the patients. Hypertriglyceridemia was observed in 5 out of 6 patients, antihypertensive therapy was needed in 50%. One patient died from primary pulmonary hypertension. PMID- 2106599 TI - Age-related decline of plasma bioavailable testosterone in adult men. AB - Plasma bioavailable and total testosterone (T), gonadotropins (FSH, LH) and prolactin (PRL) were determined in 70 ambulatory men subdivided into 3 groups according to age: group I (n = 22; age 20-35 yr), group II (n = 22; age: 36-50 yr) and group III (n = 26; age 51-70 yr). Bioavailable T levels declined significantly with age (r = -0.42; P less than 0.01) while those of total T decreased less significantly (r = -0.28; P less than 0.05). In addition, the decrease of bioavailable T occurred earlier. FSH was shown to increase with age (r = 0.41; P less than 0.01) whereas LH and PRL were not found to change significantly. Bioavailable T was correlated with total T (r = 0.25; P less than 0.05) and inversely correlated with FSH (r = -0.26; P less than 0.05). No correlation could be demonstrated between LH and either bioavailable or total T. In view of the age-related increase of sex hormone binding globulin, a fact generally observed in the literature, bioavailable T may be considered a more reliable index than total T for the evaluation of T production. Thus it may be concluded that the early decrease of bioavailable T in ambulatory men not known to have any pathology or any medication altering testicular function corresponds in fact to age-related decline of T secretion by the testes. PMID- 2106600 TI - Single-cannula venovenous bypass for respiratory membrane lung support. AB - Clinical use of a single cannula would make extracorporeal membrane oxygenation simpler and less aggressive. It would probably limit the occurrence of the complications of currently used techniques (double-cannula, venoarterial, or venovenous bypass). In this experimental study an original system is described that is composed of a single cannula, an alternating clamp, and a nonocclusive roller pump, the characteristics of which permit its use as a venous reservoir. To overcome the limitations of the oxygenation in any venovenous bypass, we used the method of "apneic oxygenation" through the natural lungs, which we previously proved efficient in infants and children. The optimal setting of the alternative clamp was first tested in vitro to obtain the maximal flow in the circuit and the minimal amount of recirculation. The single-cannula bypass then was compared with a two-cannula circuit regarding the efficiency of carbon dioxide removal and the hemodynamic consequences. At less than 50% of the maximal speed of the pump, flows were equivalent in both types of circuits. The efficiency of carbon dioxide removal was only slightly decreased by the use of a single cannula (30 +/- 2 ml/min versus 36 +/- 2 ml/min with two cannulas). This could easily be offset by increasing the gas flow/blood flow ratio in the oxygenator. Arterial carbon dioxide tension was maintained at normal levels in both types of circuits. Hemodynamic condition was only slightly affected by the alternative flow of the bypass. This system of single-cannula membrane lung support thus seems to be adequate for clinical use. PMID- 2106601 TI - The clinical value and risks of lung biopsy in children with congenital heart disease. AB - A retrospective review was made of 59 open lung biopsy specimens taken between 1984 and 1988 from children with congenital heart disease who were at risk for pulmonary vascular disease. Thirty-seven patients (ranging in age from 3.5 months to 23 years; median age, 14 months) had a primary left-to-right shunt (group A) and 22 patients (ages 1 to 15 years) had palliated cyanotic heart disease (group B). Forty-five of the lung biopsy specimens were requested as frozen sections. In both groups lung biopsy specimens were graded by the Heath-Edwards classification and correlated against preoperative hemodynamic data and outcome. In group A patients, carefully measured pulmonary vascular resistance and pulmonary/systemic vascular resistance ratio were reliable indicators of the structural state of the pulmonary vascular bed, obviating the need for routine lung biopsy. Pulmonary/systemic vascular resistance ratios greater than 0.45 accurately predicted all patients with irreversible pulmonary vascular disease, and pulmonary vascular resistance greater than 7 units.m2 accurately predicted all but one case of disease. Reversibility of pulmonary vascular changes is not synonymous with immediate postoperative survival: Fatal postoperative pulmonary hypertensive crises occurred in the presence of reversible pulmonary disease. Of those considered for the Fontan procedure, a mean pulmonary artery pressure less than 30 mm Hg and pulmonary vascular resistance less than 3 units.m2 correlated with Heath-Edwards grade I or normal lung biopsy results. In 36% of group B patients, reliable assessment of pulmonary vascular resistance could not be made, indicating a possible need for open lung biopsy procedures. When lung biopsy procedures were used as an isolated procedure, they were more dangerous (20% mortality, 13% morbidity) than previously reported. Intraoperative frozen sections are not adequate to accurately assess pulmonary vascular changes (9% error); serial paraffin sections are required. PMID- 2106602 TI - T cell activation in the elderly: evidence for specific deficiencies in T cell/accessory cell interactions. AB - We studied T cell activation in the healthy aged (greater than 70 years) by examining lymphocyte proliferative responses to various mitogenic stimuli in accessory cell (AC)-dependent and AC-independent systems. Results show that despite a near normal response to the anti-CD3 monoclonal antibody (mAb) OKT3, peripheral blood mononuclear cells (PBM) from the elderly exhibit a profound reduction in phytohaemagglutinin (PHA)-responsiveness (approximately 30% of young adults). This deficit becomes even more severe at suboptimal doses of PHA. Adding exogenous interleukin-2 (IL-2) or pretreating the AC population with gamma interferon (IFN-gamma) returns the level of proliferation to that seen with young adults. Furthermore, replacing "old" AC with AC from young adults or with U937 (a monocytic cell line) in T cell/AC cell-mixing experiments restores PHA responsiveness in 70% of cases. On the other hand, AC from the aged fully support PHA responses in T cells from young adults. In AC-depleted cultures, purified T cells from the aged respond normally to the co-mitogenic stimuli, PHA + PMA. Taken together, these results suggest that the age-associated diminution in PHA responsiveness is due, at least in part, to specific deficiencies in T cell/AC communication. PMID- 2106603 TI - Cardiorenal actions of endothelin, Part II: Effects of cyclooxygenase inhibitors. AB - The effects of cyclooxygenase inhibitors (meclofenamate and indomethacin) on endothelin-induced changes in renal function were evaluated in pentobarbital anesthetized female rats. Two groups (n = 5/group) of rats were evaluated: one group received a continuous intravenous infusion of meclofenamate (0.03 mg kg-1 min-1) and the second group received a bolus injection of indomethacin (5 mg/kg). Following surgery, rats were allowed 60 min to stabilize and 3 X 20 min control clearances collected. Endothelin-1 (100 eta kg-1 min-1) was then added into the infusate for 30 min. Neither meclofenamate nor indomethacin caused significant changes on endothelin-induced systemic vasoconstriction; blood pressure increased from 107 +/- 3 to 136 +/- 2 mmHg (p less than 0.01) with endothelin alone, from 103 +/- 6 to 135 +/- 6 mmHg (p less than 0.01) with endothelin plus meclofenamate, and from 105 +/- 6 to 131 +/- 10 mmHg (p less than 0.01) with endothelin plus indomethacin. Similarly, endothelin-induced decreases in glomerular filtration rate (GFR) were not affected by either meclofenamate or indomethacin; GFR decreased from 2.7 +/- 0.2 to 0.8 +/- 0.3 ml/min (p less than 0.01) with endothelin alone, from 2.3 +/- 0.5 to 0.7 +/- 0.4 ml/min (p less than 0.01) with endothelin plus meclofenamate, and from 2.6 +/- 0.4 to 0.6 +/- 0.4 ml/min (p less than 0.01) with endothelin plus indomethacin. Baseline excretion rates of sodium, potassium and urine volume were also not affected by the inhibitors of cyclooxygenase. These data demonstrate that, under the conditions of the current study, endothelin-induced changes in renal and cardiovascular function are not affected by inhibiting prostaglandin production. PMID- 2106604 TI - A follow-up study of an outbreak of non-A, non-B hepatitis in a plasmapheresis unit. AB - A cluster of acute non-A, non-B hepatitis comprising 12 blood donors was diagnosed in a plasmapheresis unit. Nine cases were followed-up for 2-5.5 years and seven out of them progressed to chronicity, as judged by biochemical abnormalities. In six, liver biopsy was performed 1 year after the acute disease revealing chronic active hepatitis in two, chronic persistent hepatitis in two, chronic lobular hepatitis in one and normal liver in one. Repeated biopsies showed progression to cirrhosis in one case of chronic active hepatitis, and resolution of the disease in another one, while in the remaining patients liver morphology remained unchanged. Circumstantial epidemiologic evidence suggests a single agent being the cause of the outbreak, which resulted in a broad spectrum of liver disease. PMID- 2106605 TI - State Medicaid ICF-MR utilization and expenditures in the 1980-1984 period. AB - State Medicaid ICF-MR expenditures have shown a dramatic increase during the 1980 1984 period. The ICF-MR bed capacity declined slightly relative to the total state population, whereas the number of ICF-MR Medicaid recipients increased somewhat during the period. Regression analysis showed a strong positive relation with higher ICF-MR utilization and expenditures. Higher Medicaid reimbursement rates and greater proportions of employees who were unionized were also associated with higher state expenditures. Some states may be using limits on ICF MR bed supply and reimbursement rates to constrain their overall Medicaid ICF-MR program costs. PMID- 2106606 TI - Manifestation of diabetes mellitus on mouse follicular and pre-embryo development: effect of hyperglycemia per se. AB - Animal models of diabetes mellitus during pregnancy have repeatedly suggested that maternal hyperglycemia was teratogenic during organogenesis, and thus may contribute to diabetic teratogenesis. However, little attention has been focused on the effects of hyperglycemia on pre-organogenic development. In this report, we examine the effect of hyperglycemia (950 mg glucose/dL) on the development of mouse pre-embryos in vitro. B6C3F1 mice were superovulated with 5 U pregnant mare serum gonadotropin (PMSG) followed by 5 U human chorionic gonadotropin (hCG) 48 hours later. Two cell pre-embryos were recovered 48 hours later, pooled together, and randomly assigned to different treatment groups. Cultures were performed in HAM's F-10 media (Gibco, Long Island, NY) with 0.1% bovine serum albumin (BSA; Sigma, St. Louis, MO) BSA at 37 degrees C in an atmosphere of 5% CO2, 5% O2, and 90% N2 with 15 to 30 embryos per milliliter of culture fluid. Cultures were viewed daily at 24, 48, and 72 hours after culturing, with recording of the development. Compared with control pre-embryos (n = 216), embryos cultured in elevated glucose levels (950 mg/dL) (n = 226) demonstrated marked growth retardation as assessed both by (1) distribution of developmental stages at each observation point (24 hours, P less than .001; 48 hours, P less than .006; 72 hours, P less than .001); and (2) a difference in the average rank sums indicating a delay in maturation (P less than .005). In a second protocol group, pre-embryos were cultured in an equivalent amount of L-glucose; no impairment in development compared with controls was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106608 TI - Validity of transition-zone dosimetry at high atomic number interfaces in megavoltage photon beams. AB - Measurement of dose or dose perturbation factors at high atomic number interfaces are usually performed with a thin-window parallel-plate ion chamber. In a transition region, under nonequilibrium conditions, accuracy of ion chamber readings for the dose measurements has often been questioned. This paper critically analyzes the factors (stopping power ratio and charge collection) for the dose measurements at interfaces. Monte Carlo simulations were performed to investigate the secondary electron spectrum produced by photon beams and to calculate the stopping power ratios at the point of measurement. The validity of dose measurements was studied for the photon beams in the range of Co-60 gamma rays to 24-MV x rays at bone and lead interfaces with polystyrene, using thermoluminescent dosimeters, extrapolation chamber and several types of commercially available parallel-plate ion chambers. It is observed that for energies greater than 10 MV most parallel-plate chambers can be used to measure dose accurately. At lower energies, however significant differences between measured doses with different detectors were noticed. It is suggested that at high-Z interfaces and lower energies, the dose measurements should be performed with ultrathin-window parallel-plate ion chambers or extrapolation chambers. PMID- 2106609 TI - Characteristics of photon beams from Philips SL25 linear accelerators. AB - The Philips SL25 accelerator is a multimodality machine offering asymmetric collimator jaws and a new type of beam bending and transport system. It produces photon beams, nominally at 6 and 25 MV, and a scattered electron beam with nine selectable energies between 4 and 22 MeV. Dosimetric characteristics for the 6- and 25-MV photon beams are presented with respect to field flatness, surface and depth dose characteristics, isodose distribution, field size factors for both open and wedged fields, and narrow beam transmission data in different materials. PMID- 2106607 TI - Effect of pravastatin, an HMG CoA reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by their apolipoprotein composition. AB - This study compares the effects of cholestyramine (16 g/d) and pravastatin (40 mg/d) on lipoprotein particles defined by their apolipoprotein composition (Lp A I, Lp A-II:A-I, Lp E:B, and Lp C-III:B). Analysis was performed after 4, 8, and 12 weeks of therapy. Low-density lipoprotein (LDL) cholesterol decreased by 25.1% to 35.0% with cholestyramine and 26.2% to 30.7% with pravastatin, while triglycerides decreased slightly with pravastatin therapy and increased slightly during cholestyramine administration. The fall in cholesterol was mainly due to a decrease in very-low-density lipoprotein (VLDL) and LDL cholesterol; high-density lipoprotein (HDL) cholesterol increased. Apolipoprotein B was reduced dramatically (by 21.7% to 30.5% with cholestyramine and 27.7% to 37.4% with pravastatin). No significant effect on apolipoproteins C-III and E was observed with cholestyramine, while pravastatin reduced these parameters slightly. Apolipoprotein A-I increased during therapy with both drugs, while apolipoprotein A-II was slightly decreased. Although the drugs had nearly the same effects on plasma lipids, their influence on lipoprotein particles defined by their apolipoprotein composition was substantially different. Lp A-II:A-I was increased by both drugs (+8.1% to +41.2% for cholestyramine and +7.2% to +32.6% for pravastatin). Lp A-I was also increased with both drugs, but cholestyramine had a more constant and pronounced effect than pravastatin (+15.1% to +21.7% for cholestyramine and +1.7% to +13.0% for pravastatin). Lp E:B and Lp C-III:B were consistently decreased by pravastatin (-10.2% to -36.5% for LP E:B and -7.2% to 20.9% for Lp C-III:B), while cholestyramine had variable effects on these particles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106610 TI - A study of effective attenuation coefficient for calculating tissue compensator thickness. AB - Dose uniformity throughout the treatment volume is essential to precision radiation therapy. Tissue compensators are often used as a means to eliminate dose nonuniformity resulting from surface contour irregularities. This paper evaluates the accuracy of using an effective attenuation coefficient for calculating the thickness of missing tissue. This coefficient is found to vary strongly with thickness of missing tissue when the initial depth is situated in the buildup region. The use of a single attenuation coefficient produces errors as high as 54% in the calculated compensator thickness when 10-MV x rays are used. At depths greater than the depth of maximum dose, the attenuation coefficient remains a function of field size, not the initial depth. PMID- 2106611 TI - Measurement of dose in the buildup region using fixed-separation plane-parallel ionization chambers. AB - Accurate measurement of dose at the surface of a phantom and in the buildup region is a difficult task but one that is important for the proper treatment of patients. The instruments of choice for these measurements are extrapolation chambers but few institutions have these instruments at their disposal. As a result, fixed-separation plane-parallel ionization chambers are most commonly used for this purpose. Recent papers have re-emphasized the inaccuracies in the measurement of dose in the buildup region of normally incident photon beams when using fixed-separation plane-parallel ionization chambers. Data for Co-60, 6-, 10 , 18-, and 24-MV photon beams are presented that show the magnitude of this over response in the buildup region for several commercially available plane-parallel ionization chambers versus results obtained using both an extrapolation chamber and LiF thermoluminescent detectors. Differences in the percent depth dose at the surface of a phantom of greater than 19% were found for one of the chambers. All chambers over responded in the buildup region to some degree based upon their internal dimensions. The appropriateness of published corrections for these chambers is evaluated and guidelines for the accurate measurement of dose in the buildup region are presented. PMID- 2106612 TI - Electron beam characteristics on a Philips SL25. AB - Dosimetry measurements at nominal electron energies of 4, 6, 8, 10, 12, 15, 17, 20, and 22 MeV were made for different sized, open-sided applicators on two Philips SL25 linear accelerators. Measurements include beam flatness, percentage depth dose, surface dose, isodose curves, field size dependence, output at extended distances, virtual source position, and required low melting point alloy thickness for field shaping. These measurements are presented to document the characteristics of electron beams with a new type of applicator design on this series of Philips accelerators. PMID- 2106613 TI - Radiation quality investigations around a neutron therapy beam, using a high pressure ionization chamber. AB - The mean quality factor (Q) and the dose mean linear energy transfer [LET (LD)] a few centimeters outside a neutron therapy beam have been measured using a high pressure ionization chamber. Measurements have been carried out in air, 5 and 100 cm outside the treatment field edge on the patient plane for p(46)-Be neurons and are compared with the results obtained at the same points with a low-pressure proportional counter (Rossi counter) and a Bonner spheres system. General agreement is found between these independent methods. The dose equivalent at 5 and 100 cm distances outside the field edge is 2% and 0.4% of the dose equivalent at the isocenter. Measurements were also performed at the same points as a function of proton energy on the Be target. Proton energies of 25-46 MeV on Be were applied. The results indicate increase in the mean quality factor at proton energies below 30 MeV. PMID- 2106614 TI - Dynamic wedge field techniques through computer-controlled collimator motion and dose delivery. AB - Clinical treatment planning situations arise which require different wedge angles within segments of a single therapeutic x-ray field. Idealized wedge-shaped dose distributions, including combination of several wedge segments of different angle within a single field, are generated and delivered through computer control of asymmetric collimator motion and dose per field segment. A dual-pass technique is introduced to provide improved adherence to the prescribed isodose distribution. Dynamic wedge distributions are verified by film densitometry and ionization chamber measurement. These results suggest the potential importance of this technique as an added clinical radiotherapy tool. PMID- 2106615 TI - Update: tuberculosis elimination--United States. PMID- 2106616 TI - Update: influenza--United States, 1989-90. PMID- 2106617 TI - Alcohol-related mortality and years of potential life lost--United States, 1987. PMID- 2106618 TI - Alcohol-related disease impact--Wisconsin, 1988. PMID- 2106619 TI - Microsporidian keratoconjunctivitis in patients with AIDS. PMID- 2106620 TI - Methylated oxypurines and induction of differentiation of murine erythroleukemia cells. AB - Murine erythroleukemia cell lines derived from Friend virus infected mice can be induced to differentiate in vitro by numerous agents. Among these compounds are certain naturally occurring purines such as hypoxanthine or 1-methylhypoxanthine. We have extended these studies to other modified oxypurines and have identified some areas of cell regulation with which they may be interacting. Monomethylated derivatives of guanine, hypoxanthine or xanthine are active as inducers of differentiation. Excluding hypoxanthine, the parent oxypurines guanine and xanthine are ineffective in inducing differentiation. The dimethyl- and trimethylxanthine derivatives are also inactive as inducers. The methylated oxypurines are not metabolized to nucleotides by the cell and, therefore, probably do not interact with nucleic acid synthesis directly. We have investigated one cellular process of possible regulatory significance with which they do interact. ADP-ribosylation has been implicated in control of gene expression and differentiation. The methylated oxypurines inhibit this reaction, as measured in permeabilized cells, in the same concentration range at which they are effective as inducers of differentiation. Additionally, 1-methylguanine and 7 methylguanine decrease incorporation of mannose and glucosamine into glycoprotein and into dolichol-oligosaccharide precursors. These effects may be related to cell surface alterations observed during differentiation. PMID- 2106622 TI - Late ontogenetic development of adenosine A1 receptor coupling to associated G proteins in guinea pig cerebellum but not forebrain. AB - The ontogenetic profile of [3H]forskolin and [3H]cyclohexyladenosine [( 3H]CHA) binding sites in guinea pig forebrain and cerebellum was investigated. G-protein interactions of these binding sites were also examined by analyzing 5' guanylylimidodiphosphate (Gpp(NH)p) interactions with [3H]CHA and [3H]forskolin binding. In forebrain, similar binding characteristics of [3H]CHA and [3H]forskolin binding are observed between the developmental stages E36 (the earliest time point studied) through to adult (P28, the latest time point studied), although transient increased binding of both ligands is observed just prior to birth. Scatchard analysis of binding isotherms reveal that this transient rise just prior to birth is due to an increase in the number of binding sites (Bmax) with little or no change in receptor affinity (Kd). In contrast, in cerebellum both [3H]CHA and [3H]forskolin binding remains at a relatively low level until just prior to birth when a dramatic increase of binding of both ligands is observed which continues to increase up to P28. Scatchard analysis of binding isotherms reveal that such changes in binding of both ligands are largely due to increases in Bmax and not Kd, although Scatchard analysis of [3H]CHA binding to cerebellar E51 membranes reveals an absence of higher affinity [3H]CHA binding sites. Gpp(NH)p did not affect [3H]forskolin binding. Gpp (NH)p displacement profiles of [3H]CHA binding reveal a maximum (adult) inhibition of [3H]CHA binding (approximately 80% displacement) at all time points (E36 through P28) in forebrain membranes, but not in cerebellar membranes. In cerebellum, displacement of [3H]CHA binding by Gpp(NH)p is much greater after birth than before birth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106623 TI - High frequency of spontaneous Minute mutations detected in the F1 progeny of interstrain matings between a recombination-defective mei-9L1 and the y w m f/sc8(y+) Y BS; dp strain of Drosophila melanogaster. AB - The yield of spontaneous Minute mutations was recorded in the F1 progeny of interstrain (reciprocal) and intrastrain matings between a recombination- and excision repair-defective mei-9L1 (mei-9) strain and the y w m f/sc8(y+) Y BS; dp (ywmf-2) strain of Drosophila melanogaster. As a comparison, interstrain matings between a postreplication repair-defective st mus(3)302D1 (mus(3)) strain and the ywmf-2 strain were also studied for Minute mutations. The results show that: (1) a strikingly high frequency of Minute mutations is observed in the progeny of mei 9 female X ywmf-2 male crosses, but not in that of ywmf-2 females X mei-9 males; (2) no such difference exists in the progeny of intrastrain matings; and (3) there exists no marked inequality of Minute frequencies in the progeny of reciprocal crosses of mus(3) and ywmf-2 strains. PMID- 2106621 TI - Microsomal redox systems in brown adipose tissue: high lipid peroxidation, low cholesterol biosynthesis and no detectable cytochrome P-450. AB - The presence of redox systems in microsomes of brown adipose tissue (BAT) in cold exposed rats was investigated and compared with liver. BAT microsomes showed high activity of lipid peroxidation measured both by the formation of malondialdehyde (MDA) and by oxygen uptake. NADH and NADPH dependent cytochrome c reductase activity were present in both BAT and liver microsomes. Aminopyrine demethylase and aniline hydroxylase activities, the characteristic detoxification enzymes in liver microsomes could not be detected in BAT microsomes. BAT minces showed very poor incorporation of [1-14C]acetate and [2-14C]mevalonate in unsaponifiable lipid fraction compared to liver. Biosynthesis of cholesterol and ubiquinone, but not fatty acids, and the activity of 3-hydroxy-3-methyl glutaryl CoA reductase appear to be very low in BAT. Examination of difference spectra showed the presence of only cytochrome b5 in BAT microsomes. In addition to the inability to detect the enzyme activities dependent on cytochrome P-450, a protein with the characteristic spectrum, molecular size in SDS-PAGE and interaction with antibodies in double diffusion test, also could not be detected in BAT microsomes. The high activity of lipid peroxidation in microsomes, being associated with large oxygen uptake and oxidation of NADPH, will also contribute to the energy dissipation as heat in BAT, considered important in thermogenesis. PMID- 2106624 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 11-1990. A 38-year-old woman with fever, skin lesions, thrombocytopenia, and venous thromboses. PMID- 2106625 TI - Cost effectiveness and Medicare coverage. PMID- 2106626 TI - Segmental and developmental regulation of a presumptive T-cell oncogene in the central nervous system. AB - Although most proto-oncogenes such as c-myc are involved in cell proliferation, being expressed in a wide range of tissues as well as in progenitors of transformed cells, others may normally function in cellular differentiation. We now report on a gene on human chromosome 11, at the junction of the T-cell tumour associated chromosomal translocation t(11; 14) (p15; q11) and known as the 11p15 gene or Ttg, which is believed to be involved in the pathogenesis of the tumour. It has two transcriptional promoters (both retained by the translocated allele) and is expressed in tumour cells with neuro-endocrine properties, suggesting that normal expression may occur in nerve cells. Using fusion constructs of one 11p15 promoter and lacZ in transgenic mice, we found that the gene is expressed in a segment-specific manner in rhombomeres of the developing mouse hind-brain. During subsequent development, the gene is more widely expressed, again in precisely defined regional patterns, but in post-mitotic neurons confined to the central nervous system. Thus, this presumptive T-cell oncogene is both developmentally regulated and segmentally restricted in a tissue different from that in which the original tumour arose. PMID- 2106628 TI - A second B cell-specific enhancer 3' of the immunoglobulin heavy-chain locus. AB - The expression of immunoglobulin heavy-chain (IgH) genes is generally thought to be regulated by the combination of the VH promoter with the enhancer element which is located in the JH-CH intron. This is probably an oversimplification: there are cell lines that transcribe IgH genes despite the deletion of the intron enhancer. These findings could imply that other enhancer element(s) exist in the IgH locus. Here we show that a strong B-cell-specific enhancer is indeed located at the 3'-end of the rat IgH locus, 25 kilobases downstream of C alpha. This enhancer should be retained downstream of all rearranged IgH genes, regardless of the VH or CH segment used. Taken together with analogous findings for the mouse kappa locus, the results prompt a re-evaluation of the mechanism of regulation of immunoglobulin gene transcription. Furthermore, unlike the intron-enhancer, the IgH 3' enhancer would become linked to a c-myc that rearranges into an IgH switch region. The IgH 3' enhancer could therefore play a part in the activation of the translocated c-myc genes in rat immunocytomas, mouse plasmacytomas and Burkitt lymphomas. PMID- 2106627 TI - Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. AB - Atherosclerosis in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators--agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor). Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium. Recently, 'cell-modified' or 'oxidized' low density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators. PMID- 2106629 TI - Methods of ovulation induction. AB - The results of ovulation induction in patients with ovulatory dysfunction were reviewed for a one year period. Eighty-six women were assigned to four groups: secondary amenorrhea, anovulation, oligo-ovulation, and luteal phase defect/short luteal phase (LPD). All patients were monitored with basal body temperature (BBT) graph, postcoital testing, and ultrasonic scanning of ovarian follicles. All patients received therapy with clomiphene citrate (CC) for a minimum of four cycles and 13 patients conceived. Fifty patients were offered additional therapy with human menopausal gonadotropins (HMG-HCG). Seventeen completed a minimum of four cycles, and 13 conceived. The number of CC-treated patients with poor mucus quality in the face of adequate follicular development was 24, or 48%. The overwhelming problem with ovulation induction when CC failed was the large number of patients who dropped out of therapy, 48%. In summary, close monitoring during ovulation induction to confirm ovulation, and assess mucus quality and luteal function allow detection and correction of inadequate response. Induction of ovulation can be highly successful if patients can follow through and complete protocols of therapy. PMID- 2106631 TI - Role of leukocytes and 5-lipoxygenase products in induction of cerebral edema. PMID- 2106630 TI - The effect of timing of intrathecal fibrinolytic therapy on cerebral vasospasm in a primate model of subarachnoid hemorrhage. AB - The effect of intrathecal tissue plasminogen activator administered at times from 0 to 72 hours after subarachnoid hemorrhage on the development of cerebral vasospasm in primates was examined. Thirty monkeys were randomly assigned into one of five equal groups: a control group that underwent subarachnoid hemorrhage alone, and 0-, 24-, 48-, and 72-hour treatment groups that received 0.75 mg of tissue plasminogen activator at those times after baseline cerebral angiography and subarachnoid hemorrhage on the right side. Seven days later angiography was repeated and the animals were killed. One animal in the 72-hour group developed a delayed ischemic deficit on Day 7 after subarachnoid hemorrhage. In the control and 72-hour groups significant vasospasm occurred in most of the major, right cerebral arteries (P less than 0.05), but no significant vasospasm developed in the 0-, 24-, and 48-hour groups. Although a large subarachnoid clot remained in the control animals, most clot had been dissolved in all treatment groups. Lysing of subarachnoid hematoma with intrathecal tissue plasminogen activator within 72 hours of subarachnoid hemorrhage is effective in preventing vasospasm in primates. PMID- 2106632 TI - Incidence and etiology of conjunctivitis in Navy recruits. AB - Recruit sick call at the Naval Training Center, Great Lakes, Illinois was monitored for cases of conjunctivitis during two 2-week periods in March in 1981 and 1982. Twenty-three cases were detected. The incidence of conjunctivitis was 1.1 cases per 1000 recruits per week. Peak incidence occurred during the third and fourth weeks of training and two recruit companies had multiple cases. Conjunctival cultures for viruses and Chlamydia trachomatis were negative in all cases. Concurrent cultures of conjunctival exudate were obtained from 12 cases. Haemophilus influenzae was isolated from three of these cases and Streptococcus pneumoniae from one. Despite the high percentage of negative cultures, the clinical characteristics and pattern of occurrence of conjunctivitis in Navy recruits suggest that it is caused by an infectious agent or agents. PMID- 2106633 TI - The needs of a disaster medical assistance team for environmental support services. AB - The National Disaster Medical System (NDMS) was formed to provide medical assistance to civilian disaster areas. Disaster Medical Assistance Teams (DMAT) are subunits of NDMS and could be transported to the disaster area. For DMAT to function, a team must be able to provide for itself. The Bethesda DMAT established a Logistical Support Group within the team to provide these services. This paper identifies the mission and personnel of the Logistical Support Group. PMID- 2106634 TI - Delayed sleep phase syndrome--criminal offense in the military? AB - Delayed Sleep Phase Syndrome (DSPS) is a circadian rhythm displacement that results in an inability to get to sleep at night and awake in the morning at desired times. This case report is the first to document a criminal proceeding against a patient because of this medical condition. PMID- 2106635 TI - Post-traumatic stress disorder among Special Forces Vietnam veterans. AB - Fifty-seven Special Forces Vietnam Veterans were studied to determine if special selection and rigorous training affected the frequency and pattern of predictors of post-traumatic stress disorder (PTSD). No absolute immunity to PTSD was conferred. Frequency (25%) and predictors of PTSD were similar to those reported for other groups of Vietnam Veterans. Symptoms of PTSD were associated with poorer pre-service relationships, being wounded, being wounded after return from R&R, having friends missing in action, feeling guilt over the death of a friend, lack of emotional preparation to leave the unit or service, and failure to discuss feelings upon return from Vietnam. PMID- 2106636 TI - Common sense strategies for accident and injury prevention. AB - The author presents a comprehensive set of initiatives and strategies for military line and medical commanders for developing effective injury prevention programs. These are not necessarily taken from preexisting written policies and instructions. Rather, they are based on his experiences in the preventive and occupational medicine field. These recommendations are for military personnel, their dependents, and federal civilian employees, and should be applied at work, at home, and during recreation. PMID- 2106638 TI - HIV preventive medicine services and public health interventions: the Bethesda experience. AB - A basic Public Health approach to the Human Immunodeficiency Virus (HIV) epidemic has been considered by many to be the most appropriate initial strategy against the spread of this infection. Comprehensive Preventive Medicine services were implemented at Naval Hospital Bethesda, which utilized a sexually transmitted disease (STD) model and included: counseling and education; sexual contact interviews and spouse evaluations; Blood Bank Look Back tracking of donated blood; reporting of notifiable diseases; and screening of transfusion recipients, STD cases, and other at-risk populations. This coordinated approach is highly efficient and capable of evaluating the increasing numbers of HIV-positive individuals. PMID- 2106637 TI - Kaposi's sarcoma with emphasis on gastrointestinal manifestations. AB - Kaposi's Sarcoma is a rare disease. Gastrointestinal involvement of Kaposi's is very unusual. With the increasing incidences of Acquired Immune Deficiency Syndrome (AIDS) it has become more common in both civilian and military practice. The practicing physician should be aware of gastrointestinal symptoms of Kaposi's Sarcoma and their treatment. PMID- 2106639 TI - The prevention of softball injuries: the experience at Yokota. AB - Softball injuries occur in a predictable pattern. Review of Emergency Room records at Yokota AB Hospital for three summers showed a high incidence of ankle injuries. Sliding is the cause of many of these injuries. Common sense interventions should reduce the incidence of softball injury. Use of low profile bases or the outlawing of sliding are reasonable interventions that should be considered by policy makers. PMID- 2106640 TI - The impact of dedicated physician staffing on patient flow and quality assurance parameters in an Air Force emergency department. AB - A retrospective audit of 17,028 emergency charts at USAF Medical Center, Scott was performed over two time periods to compare patient waiting times and selected quality assurance parameters with two methods of physician staffing. Phase 1 consisted of 4 months when the Emergency Department (ED) was manned with five physicians assigned only to that department. Non-departmental physicians supplemented the full-time staff. Phase 2 was the corresponding 4 months the following year when the ED was staffed with six emergency physicians, and non emergency physician coverage was minimal. The difference in daily census between the two periods of time was not statistically significant. The time required to be seen by a physician decreased from an average of 25.6 minutes per patient in phase 1 to 13.7 minutes per patient in phase 2. Time to disposition also decreased from 71.9 minutes per patient in phase 1 to 59.5 minutes per patient in phase 2. In the second phase the number of "positive" x-ray findings increased, while the number of incomplete charts and patients who left without being seen by a physician diminished. PMID- 2106641 TI - An evaluation of prenatal care utilization in a military health care setting. AB - An assessment of prenatal care and birth outcomes was performed for a sample of 7,599 births at a military hospital between 1982 and 1985. Prenatal care patterns were similar to a civilian Health Maintenance Organization study's. Less adequate levels of prenatal care were significantly associated with higher risks of neonatal mortality and low birth weight. Five independent risk factors for receiving less adequate care were identified by multivariate analysis: 1) young maternal age (less than age 20), 2) black race, 3) residence off post, 4) high risk combinations of age and parity, and 5) residence in low-income census tracts. PMID- 2106642 TI - The operational realities and lessons learned in setting up a functional medical unit, self-contained transportable operating room to support a fixed facility. AB - Routine surgical care at Cutler Army Community Hospital (CACH), Fort Devens, Massachusetts was interrupted for almost 2 months while the operating room floors of the hospital were renovated. Surgical capabilities were maintained utilizing the field resources of the 46th Combat Support Hospital (CSH). This initiative required the exceedingly close coordination and combined efforts of both medical commands superimposed on a matrix of finite installation support and community acceptance, fostered by a proactive, highly visible public relations program. The joint venture was an unequivocal success in terms of maintaining the continuity of operations, demonstrating the real-life capabilities of surgical field equipment, and providing invaluable first-hand "do's and don'ts" training experience to the soldiers involved in the project. A "lessons learned perspective" of the planning and implementation phases is presented that provides beneficial real-life reference information and resource data. PMID- 2106643 TI - Gallstone jejunal perforation: surgical implications. AB - Spontaneous biliary-enteric fistulization is a rare complication of cholelithiasis. Much rarer yet is spontaneous jejunal perforation from an impacted gallstone. A case is presented from a suburban community general hospital. An aggressive surgical approach is endorsed and the impact of current economic constraints on surgical philosophy is reviewed. PMID- 2106644 TI - Biliary tract melanoma. AB - A case of melanoma of the upper extremity with a solitary metastasis to the common bile duct is reported. A comprehensive review of melanoma in the biliary tree is presented. Antemortem diagnoses of such cases are rare but are associated with a high percentage of disease clinically confined to the biliary tree. Patients with such lesions have survived long periods of time after palliative surgery. Therefore, surgical resection is recommended as the treatment of choice in patients able to tolerate surgery. PMID- 2106645 TI - Cardiac arrhythmias and electrocardiographic changes during upper and lower gastrointestinal endoscopy. AB - Ninety-two patients undergoing upper and lower gastrointestinal endoscopy were monitored with holter recording for electrocardiographic changes during the procedures. The electrocardiographic changes were seen in 20.6% of the patients. These included cardiac arrhythmias in 16.2% and ischemic ST-T changes in 4.4% of the patients. The incidence of these changes was more in patients with cardiac (36%) or pulmonary disease (25%) than in patients with no clinical cardiac or pulmonary problem (16%). The patients with baseline electrocardiographic abnormalities also showed higher incidence of such electrocardiographic changes during the endoscopic procedures when compared with patients with normal baseline electrocardiograms (32% vs. 16%). PMID- 2106646 TI - Military dependent medical care during World War II. AB - Dependent medical care at Army expense or at Army facilities during World War II was offered only on an emergency basis and at the discretion of the facility commanding officer. This had been the practice since 1884 when such care was specifically authorized by Congressional appropriation. Mobilization in 1898 and 1917 had brought a large number of state militiamen or inductees into the army- men who could leave their families behind. When mobilization began again in 1940, it was thought that a similar procedure would be followed. Events, however, overwhelmed the system as commanders of Army bases faced large numbers of young, pregnant wives who had followed their husbands. This had happened, in part, because of the dislocations of the Great Depression and, in part, because the wives of military inductees hoped to find work close to where their husbands were stationed. Although dependent medical care was not increased in proportion to the numbers of new dependents brought in by the war mobilization, medical care was provided for the four lower grades under the Emergency Maternity and Infant Care section of the Social Security Act of 1935. Subsequent to World War II and the experience of the Korean War, Congress saw it fit to specifically authorize medical care for dependents of military personnel as part of the soldiers' terms of employment, as a device to stimulate retention in service of both soldiers and doctors. In 1956 the United States Congress established the right at law of military dependents to medical care as specified in the Dependents' Medical Care Act.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106647 TI - Colon cancer in the active duty population. AB - Of the 140,000 cases of colorectal cancer anticipated this year, approximately 2% to 6% will occur in patients less than 40 years old. Data regarding colon cancer in this age group applies directly to the similarly aged active duty population. The problem is illustrated by two case histories. A review of the literature indicates that patients of this age group may have a worse prognosis, not due to age per se, but likely due to a combination of an advanced stage at diagnosis and a higher percentage of poorly differentiated or mucin-producing tumors. Early diagnosis remains essential for improved survival. PMID- 2106648 TI - The evaluation of urine pH in screening for asymptomatic bacteriuria in pregnancy. AB - The purpose of this prospective investigation was to determine whether an alteration in urine pH, either by itself or in combination with other rapid screening tests, could be used to identify asymptomatic bacteriuria in pregnant women. Clean catch urine specimen was used to evaluate 510 asymptomatic obstetric patients. Urine specimens were tested for pH, leukocyte esterase activity, and the presence of nitrites. The pH, leukocyte esterase activity, and nitrite reaction were evaluated singly and in combination to determine if these variables could be used to predict significant bacteriuria. Twenty-four (4.8%) patients had positive cultures for E. coli. The mean pH of the infected population was not significantly different from that of the uninfected population. The performance parameters of pH, singly and in combination with the leukocyte esteras and nitrite status, were poor. We concluded that the identification of urine pH is not of value in detecting asymptomatic bacteriuria. PMID- 2106649 TI - Clinical trial of remote radiologist services for a military installation. AB - It is often difficult to provide continuity of professional radiological services at U.S. military facilities located at a distance from major metropolitan areas. To address this problem, we have designed and evaluated a program to send x-ray films from a U.S. Army hospital to a remote site for expert radiological interpretation. Nine hundred and forty-two x-ray studies were sent by U.S. Express Mail from the Radiology Department of a U.S. Army Hospital over a 2-month period. The typed reports were sent back to the hospital through the use of a computer-to-computer telephone link within 72 hours of film transport. No studies were lost and security of all studies was maintained. This program offers a cost effective, otherwise unavailable means to provide high quality professional radiological services to U.S. military facilities both inside the United States and in foreign countries. PMID- 2106650 TI - Behavioral and psychological responses to chemical and biological warfare. AB - Understanding the behavioral and psychological responses in a chemical environment is critical to individual health and unit functioning. Reports of incidents of acute nerve agent and other organophosphate exposures and of repeated low-dose toxic exposures can provide information about psychiatric symptomatology, performance disruption, and recovery. This paper presents a review of the literature on the longer term consequences of acute and chronic exposure to nerve agents and other organophosphates. In addition, reports on psychological responses during chemical warfare training are reanalyzed to identify behavioral and psychological casualties attributed to the unique stressors of the CBW environment. PMID- 2106651 TI - Sickle cell trait and rhabdomyolysis: case report and review of the literature. PMID- 2106652 TI - Sudden death in a young woman: pulmonary thrombosis and adenocarcinoma of the lung. PMID- 2106653 TI - Case report: primary intracranial hypotension. PMID- 2106654 TI - Historical perspective on the evolution of today's military field anesthesia machine. PMID- 2106655 TI - Blood chemistry of current and previous anabolic steroid users. AB - While the use of anabolic-androgenic steroids appears to be increasing, little is known about the long-term effects of these drugs. This study compared selected blood profiles of current and former steroid-using athletes to expected values for non-drug-using populations. The results are consistent with previous research findings that steroids can have acute negative effects on liver function, lipoprotein fractions, and testosterone production. The results suggest that side effects vary widely among individuals and are drug and dose dependent. Normal function appears to return after drug use is discontinued. These data emphasize the difficulty physicians have interpreting clinical tests when dealing with those who use or have used anabolic steroids. Clearly more research is needed regarding the effects of these drugs. PMID- 2106656 TI - Prevalence of psychiatric disorders in a mandatory screening program for infection with human immunodeficiency virus: a pilot study. AB - Ninety-five randomly selected human immunodeficiency virus (HIV)-seropositive Air Force personnel were psychiatrically examined during a routine medical evaluation. Of the 95, 95% did not have acquired immunodeficiency syndrome and were largely asymptomatic; 61.1% had clinical axis I diagnoses, which included simple phobia, adjustment disorders, hypoactive sexual desire disorder, alcohol use disorder, major depression, and organic mental disorders; 30.5% had personality disorders. Significantly higher frequencies (p less than 0.05) of simple phobia and hypoactive sexual desire disorder were noted with knowledge of HIV seropositivity. Disorders that occurred more commonly than in age-matched Epidemiologic Catchment Area (ECA) participants included: simple phobia, antisocial personality disorder, alcohol abuse, and organic mental disorders. The high prevalence of major psychiatric illness in this sample supports the notion that screening for psychiatric illness, and counseling where indicated, should be integral to HIV screening programs. PMID- 2106657 TI - Joint service training for medical readiness. AB - Medical Readiness Training is of major importance in preparing to meet the challenge of medical care during wartime and national emergencies or disasters. As an alternative to simulated casualty training, the U.S. Public Health Service and the U.S. Army joined forces to provide "real world" medical care for troops during training. Although simulated training provides insight into casualty and trauma medicine, it is felt that many aspects of real medical care are often ignored or taken for granted. Providing medical care under austere field conditions provides a realistic environment and presents situations that can not be evaluated by simulated training. PMID- 2106658 TI - The role of oncogenes in cancer. AB - Researchers have accumulated evidence suggesting that most human cancers are the result of multiple events involving many genes functioning at various levels of expression over a long period of time. Recently, an important segment of cancer research has focused on oncogenes, a group of altered normal genes. The normal genes, known as proto-oncogenes, encode proteins necessary for the cell's structure, growth, and mitotic activity. Oncogenes have been found to be the activated forms of proto-oncogenes, which become activated as a result of point mutations, nucleotide deletions/insertions, or chromosomal translocations. Approximately 50 types of oncogenes have been discovered to date, and research had led us to believe that oncogenes are derived from normal genes that regulate growth and development. A general discussion of oncogenes will be presented in this review. PMID- 2106659 TI - Case for diagnosis. Myxopapillary ependymoma. PMID- 2106660 TI - Members of the medical profession should convey health and fitness advice to their line and staff counterparts. PMID- 2106661 TI - Novel families of interspersed repetitive elements from the human genome. AB - Six novel families of interspersed repetitive elements have been detected in the available human DNA sequences using computer-assisted analyses. The estimated total number of elements in the reported six families is over 17,000. Sequences representative for each family range from approximately 150 to 650 base pairs (bp) in length and are predominantly (A + T)-rich. Sequences from four families contain stretches of patchy complementarity up to 45 bp long. Member of one of the families is likely be directly involved in a multigene deletion on chromosome 14. Two of the six sequence families are homologous to 'low reiteration frequency sequences' from monkey cells, detected first in defective variants of simian virus 40. Like Alu and L1 families, the newly discovered families are probably composed of pseudogenes derived from functional genes. PMID- 2106662 TI - The nucleotide sequence of a Drosophila melanogaster enolase gene. PMID- 2106663 TI - Nucleotide sequence of the psbH gene of the cyanobacterium Synechocystis 6803. PMID- 2106664 TI - Analysis of the rat JE gene promoter identifies an AP-1 binding site essential for basal expression but not for TPA induction. AB - We have cloned the immediate-early serum-reponsive JE gene from the rat in order to study the regulation of this gene. We show that sequences of the JE promoter region confer serum-inducibility to a reporter gene. Analysis of the promoter in transient assays reveals that: i) the -141/-88 region is required for the response to the phorbol ester TPA, ii) the -70/-38 region is essential for basal activity. This latter region harbors the sequence TGACTCC, which resembles the consensus site for AP-1 binding, TGACTCA. DNA-protein binding assays indicate that the JE AP-1 site and the consensus AP-1 site have an overlapping but not identical binding spectrum for AP-1 proteins. Our data suggest that the inability of some AP-1 sites to respond to TPA is caused by subtle differences in affinity for AP-1 proteins. PMID- 2106665 TI - A high yield affinity purification method for specific RNA-binding proteins: isolation of the iron regulatory factor from human placenta. AB - We describe a simple method for the affinity purification of specific RNA-binding proteins. DNA sequences corresponding to the protein-binding site of the RNA are subcloned into an in vitro transcription vector between the T7 viral promoter and a poly(A) track. A polyadenylated RNA transcript is bound to poly(U)-Sepharose and subsequently incubated with a cellular extract prepurified on heparin agarose. Specifically adsorbed proteins are recovered in high yield and purity from the affinity matrix by high salt elution. Using this method we isolated the iron regulatory factor (IRF), a cytoplasmic protein which binds to specific palindromic elements in the 5' and 3' untranslated sequences of ferritin and transferrin receptor mRNA, respectively. Activation and binding of this regulatory factor correlates with increased transferrin receptor mRNA stability and inhibition of ferritin translation. The purified factor from human placenta migrates as a monomer in gel chromatography, but is present in equimolar amounts of two proteins with molecular weights of 95 and 100 kDa when analysed by SDS/PAGE. The two proteins are highly related as judged by the identity of their isoelectric points and their specificity to form RNA-protein complexes. PMID- 2106666 TI - Structure and expression of the Euglena gracilis nuclear gene coding for the translation elongation factor EF-1 alpha. AB - A cDNA library from the protist Euglena gracilis was used to isolate and sequence an ORF coding for the elongation factor protein EF-1 alpha. The decoded amino acid sequence (MW, 48'515) is to 75-80% identical with other eukaryotic EF-1 alpha sequences but only to 24% identical with the Euglena chloroplast EF-Tu. Homologous DNA probes interact with multiple fragments of Euglena nuclear restricted DNA typical for a multimembered gene family. We present the restriction sites map of four tef nuclear gene loci and postulate that the nuclear genome also contains tef related sequences (e.g. pseudogenes). Expression of tef gene(s) is monitored by Northern hybridization and the 5' end of a stable transcript (1.5 kb) is sequenced and shown to precede the start codon by 29 positions only. The steady state concentration of the 1.5 kb mRNA is not influenced by switching cell growth conditions from dark to light (chloroplast development). PMID- 2106667 TI - The preparation of polyamide-oligonucleotide probes containing multiple non radioactive labels. AB - Oligonucleotide probes containing multiple non-radioactive labels have been prepared by utilising and extending the methods used to prepare polyamide oligonucleotide conjugates. The probes were prepared by incorporating suitable amino acid residues, such as lysines, in the polyamide, which were then used as sites for the attachment of the non-radioactive labels. The procedures developed give control over the distance of the label from the oligonucleotide, and also the inter-label distance. The labels can be conveniently introduced while the substrate is still on the solid support. Even though fluorescent oligonucleotide probes prepared in this way carrying multiple carboxyfluorescein labels gave low levels of fluorescence due to quenching, the probes containing ten biotin labels gave a detection sensitivity of approximately 5 attomole (3 million molecules). PMID- 2106669 TI - Transcription at the ecdysone-inducible locus 2B5 in Drosophila. AB - The Broad-Complex (BR-C) of D. melanogaster, mapping at the 2B5 early ecdysone puff, mediates ecdysone-induced processes. We present here the transcriptional analysis of the locus in both wild type and representative mutants. Two well defined regions are transcribed, only one of which has a pattern consistent with the proposed 2B5 located BR-C function. The 2B5 region is actively transcribed in early third instar larvae before ecdysone levels increase. Ecdysone switches this early pattern to a complex late type which requires the presence of functional BR C product. Therefore, BR-C self-regulates its own ecdysone-induced transcription. The effect of 2B5 mutations on transcription at several intermolt, early and late puffs is also described. Null mutations at the 2B5 locus prevents ecdysone inducible transcription. This evidence supports the fact that 2B5 codes for an ecdysone-dependent transcriptional regulator. PMID- 2106668 TI - Isolation of the chicken middle-molecular weight neurofilament (NF-M) gene and characterization of its promoter. AB - We have isolated and sequenced genomic DNA clones covering the coding region of the chicken mid-size neurofilament (NF-M) gene and greater than 1 kb of its 5' upstream region. The NF-M gene contains two introns which both are located within the highly conserved C-terminal region of the rod domain. The 5' end of the corresponding mRNA was assigned to a G residue 40 nucleotides upstream of the translation start site and in appropriate distance from a potential TATA box. To functionally analyze the NF-M promoter, constructs carrying 112, 222, and 1026 nucleotides of the 5' upstream region in front of a luciferase reporter gene were tested for their capability to direct luciferase expression after transient transfection into various cell lines. Significant luciferase activity was recorded both in rat phaeochromocytoma (PC12) cells and murine fibroblasts. In PC12 cells, in which neurite outgrowth is induced by nerve growth factor (NGF), expression was stimulated up to 13-fold within 3 days of NGF treatment. This closely resembles expression of the endogenous NF-M gene in response to this hormone. PMID- 2106670 TI - Cloning regions of the Drosophila genome by microdissection of polytene chromosome DNA and PCR with nonspecific primer. AB - A simple and rapid procedure to isolate clones carrying sequences from a specific region of the polytene chromosome of Drosophila is demonstrated. The procedure involves microdissection of the region of interest, amplification of the DNA by PCR using a primer designed to prime the synthesis nonspecifically, labeling of the amplified DNA using the random primer method, and screening of a standard library with the probe to identify and isolate clones carrying sequences homologous to the dissected region. This procedure has the potential to replace the difficult procedure of microcloning, as well as facilitate chromosome walking. PMID- 2106671 TI - Nucleotide sequence of the sporulation gene spoIIGA from Bacillus subtilis. PMID- 2106673 TI - DNA sequence of a beta-glucosidase from Ruminococcus albus. PMID- 2106672 TI - The cDNA sequence of the alpha-subunit of the Chinese hamster adenylate cyclase stimulatory G-protein. PMID- 2106674 TI - Nucleotide sequence of recA gene of Aquaspirillum magnetotacticum. PMID- 2106675 TI - Dietary olive and safflower oils in promotion of DMBA-induced mammary tumorigenesis in rats. AB - Interpretation of studies comparing the efficacy of different dietary fat sources in promoting 7,12-dimethylbenz[a]-anthracene (DMBA)-induced rat mammary tumorigenesis often ignores the fact that about 4% (wt/wt) linoleic acid (18:2n 6) is required for optimal tumor promotion. We therefore fed DMBA-intubated or placebo-intubated female, Sprague-Dawley rats 20% fat diets containing 18:2n-6 (wt/wt) from either high-linoleic safflower oil (SL, 14.6% 18:2n-6), high-oleic safflower oil (SO, 3.4% 18:2n-6), olive oil (OO, 1.1% 18:2n-6), or OO supplemented with 18:2n-6 (OL, 3.4% 18:2n-6) for 16 weeks. Results indicated that OO-fed rats had longer tumor-free time, fewer tumors per rat, and lower tumor incidence compared with SO and OL. Addition of 2.3% 18:2n-6 to OO enhanced tumor promotion (p less than 0.04); SL, SO, and OL demonstrated similar tumor enhancement effect. About 74% of observed mammary tumors were adenocarcinomas; a greater number of tumors appeared in the thoracic and inguinal than in the cervical and abdominal regions irrespective of diet. These results indicate that once an optimal amount of linoleic acid is provided in the diet, oleic- or linoleic-rich oils have similar effects on promotion of mammary tumors in the rat. PMID- 2106677 TI - Pharmacokinetics of the aldose reductase inhibitor imirestat following topical ocular administration. AB - The pharmacokinetics of imirestat following topical ocular administration were evaluated in a series of studies in rabbits and dogs. Following single topical doses to both albino and pigmented rabbits, imirestat was subject to rapid uptake into the cornea followed by an initial rapid decline and then very slow elimination, with a t1/2 of approximately 130 hr. Drug was rapidly absorbed into aqueous humor, with concentrations declining to nondetectable levels by 12 hr. Imirestat was retained in the lens following topical dosing similar to that in cornea, with an apparent elimination t1/2 of 140 hr. Vitreous humor concentrations of drug were detectable for up to 72 hr after dosing. There was no apparent difference in the disposition of the drug between albino and pigmented rabbits. Bioavailability following topical dosing increased with dose, although not in a linear fashion. Formulation pH did not have an appreciable effect on ocular bioavailability. There was detectable systemic absorption following topical dosing, with plasma concentrations in rabbit being 50 to 75% of that observed following an equivalent intravenous dose. However, drug levels in the dosed eyes were significantly higher than in contralateral undosed eyes. Multiple dosing of imirestat for 6 weeks resulted in accumulation of drug in rabbit lens. Concentrations were higher in lens cortex than lens nucleus, with the time course for accumulation being different for the two. Our data suggest that imirestat penetrates into ocular tissue following topical dosing and is retained in lens and cornea, potential sites of action for the drug. PMID- 2106676 TI - Absorption enhancement of rectally infused insulin by sodium tauro-24,25 dihydrofusidate (STDHF) in rats. AB - The bile salt derivative sodium tauro-24,25-dihydrofusidate (STDHF) has been reported to promote nasal absorption of insulin. In the present study the effect of STDHF on rectal insulin absorption was investigated in rats. At concentrations of 1 and 4% (w/v) it enhanced insulin bioavailability from 0.2 +/- 0.2 (control) to 4.2 +/- 3.2 and 6.7 +/- 2.1%, respectively, as assessed by radioimmunoassay. Insulin preparations with STDHF reduced blood glucose concentrations considerably in a concentration-dependent way. Coadministration of STDHF with Na2EDTA (0.25%, w/v) tended to increase further insulin bioavailability and hypoglycemic response. Varying the site of rectal administration did not influence these parameters. PMID- 2106678 TI - Comparison of histologic nodal reactive patterns, cell suspension immunophenotypic data, and HIV status. AB - While cell suspension immunophenotypic studies are widely used as an aid in the diagnosis and classification of lymphomas and leukemias, much less attention has been directed toward interpretation of the results in reactive lymphoid proliferations. Cell suspension immunophenotypic data were therefore analyzed for 119 lymph nodes with reactive lymphoid proliferations which were divided into five major histologic categories: follicular hyperplasia, marked (FH,M), or moderate (FH); dermatopathic lymphadenopathy (DL); diffuse hyperplasia (DH); or "other." With the aid of a computer-assisted morphometer, the following were also measured and calculated: proportion of node occupied by follicles, mean relative follicle size, and mean follicle shape factor. Finally, in 57 cases, the influence of human immunodeficiency (HIV) status on the findings was analyzed. Although individual cases varied widely, cases of DL had significantly more CD3+ (T) cells, higher CD4:CD8 ratios, and fewer CD19+ (B) cells than other categories. Cases of FH,M had significantly lower CD4:CD8 ratios and more CD19+, CD10+, and transferrin receptor positive cells. Cases of FH,M and FH known to be HIV-negative had higher CD4:CD8 ratios than the HIV-positive cases. Peripheral blood CD4:CD8 ratios performed in 38 patients showed a strong correlation with nodal ratios. Morphometric data supported the correlation between follicular hyperplasia and increased proportions of CD19+, CD10+, and transferrin receptor positive cells. Rare cases had CD5:CD2 or CD3 ratios of greater than 1 or "monoclonal" kappa to lambda ratios. CD4:CD8 ratios varied widely, but aberrant T cell phenotypes were not identified. These studies demonstrate that, although great variation exists, there are certain associations between types of reactive lymphoid hyperplasia and cell suspension immunophenotypic findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106679 TI - Neuronal potentialities of cells in the optic nerve of the chicken embryo are revealed in culture. AB - Neuronal potentialities in neuroepithelial cells of the chicken embryonic optic nerve were studied in culture by using neurofilament antibodies as neuronal markers. Embryonic day-4 and -5 (E4 and E5) optic stalks were explanted in vitro. Within the first few days of culture, numerous morphologically identifiable neurons extending long neurites developed. These neurons and their processes were specifically labeled with neurofilament antibodies. Similar results were obtained by explanting only the medial portion of E7 optic stalks away from possibly contaminating cerebral or retinal tissue. To determine whether neuronal potentialities persisted at later embryonic stages, cultures of dissociated optic stalks were established at E11, E15, and E18. Neurons labeled with the various neurofilament antibodies appeared in all cultures of E11 and E15 optic stalks. However, typical neurons could not be recognized in cultures of E18 optic nerves. These results indicate that cells with neuronal potentialities are present in the embryonic optic nerve from early stages of development and persist until at least E15. Since the adult optic nerve is devoid of nerve cell bodies, our observations are consistent with the hypothesis that axons of retinal ganglion cells, which course through the optic stalk, repress neuronal potentialities within a subpopulation of precursor cells during normal development. PMID- 2106680 TI - Reversible ADP-ribosylation is demonstrated to be a regulatory mechanism in prokaryotes by heterologous expression. AB - The primary product of biological nitrogen fixation, ammonia, reversibly regulates nitrogenase activity in a variety of diazotrophs by a process called "NH4(+)-switch-off/on." Strong correlative evidence from work in Azospirillum lipoferum and Rhodospirillum rubrum indicates that this regulation involves both the inactivation of dinitrogenase reductase by dinitrogenase reductase ADP ribosyltransferase and the reactivation by dinitrogenase reductase activating glycohydrolase. The genes encoding these two enzymes, draT and draG, have been cloned from these two organisms, so that direct genetic evidence can be marshaled to test this model in vivo. The draT/G system has been transferred to and monitored in the enteric nitrogen-fixing bacterium Klebsiella pneumoniae, an organism normally devoid of such a regulatory mechanism. The expressed draT and draG genes allowed K. pneumoniae to respond to NH4Cl with a reversible regulation of nitrogenase activity that was correlated with the reversible ADP-ribosylation of dinitrogenase reductase in vivo. Thus, the expression of draT and draG genes in K. pneumoniae is necessary and sufficient to support NH4(+)-switch-off/on, and ADP-ribosylation serves as a reversible regulatory mechanism for controlling nitrogenase activity in prokaryotes. PMID- 2106681 TI - Hsp70 proteins, similar to Escherichia coli DnaK, in chloroplasts and mitochondria of Euglena gracilis. AB - The heat-shock response of Euglena gracilis was studied by pulse-labeling cells with [35S]sulfate at both the normal growth temperature (21 degrees C) and an elevated temperature (36 degrees C). Analysis of the labeled proteins by polyacrylamide gel electrophoresis indicated that the rate of synthesis of at least 3 major and 15 minor polypeptides increased in cells grown at the higher temperature. Three of the proteins appear to be immunologically related to the ubiquitous approximately 70-kDa heat-shock protein (Hsp70) family. One protein of 68 kDa was found in the cytoplasm (P68cyt) and was the major heat-shock protein in Euglena gracilis. Two other proteins, 68 and 70 kDa, were localized in mitochondria (P68mit) and chloroplasts (P70chl), respectively, and they crossreacted with a polyclonal antibody raised against the Escherichia coli heat shock protein DnaK. Like DnaK, P68mit and P70chl could be phosphorylated in vitro with [gamma-32P]ATP in a reaction that was stimulated by Ca2+. A protein with characteristics similar to those of P70chl was also found in chloroplasts isolated from maize and spinach. PMID- 2106683 TI - The SpoOA protein of Bacillus subtilis is a repressor of the abrB gene. AB - The spoOA gene of Bacillus subtilis is critical for the initial stages in the developmental cycle leading to the formation of an endospore. We show that one function of the SpoOA protein is to negatively regulate another regulatory locus, abrB, which controls the expression of many genes associated with the onset of sporulation. Purified SpoOA protein binds to a specific region of the abrB promoter and functions as a repressor of transcription in an in vitro assay. The binding of the SpoOA protein is independent of the binding of the AbrB protein, which is known to autoregulate its expression. This independence mirrors the temporal sequence of events in abrB control. PMID- 2106682 TI - Self heat shock and gamma delta T-cell reactivity. AB - We have investigated the effects of heat shock on T-cell induction and selection in vitro. We find that when cell preparations containing T lymphocytes are incubated for 30 min at 42 degrees C, a selective proliferation of gamma delta + T cells bearing the gamma delta T-cell antigen receptor follows. A greater enrichment of gamma delta + T cells is observed, upon preexposure to mycobacterial antigens in vivo. By comparing the effects of heat shock with that of mitogen or specific T-cell triggering by conventional antigens and by analyzing the gamma delta T-cell receptor genes expressed in cells that proliferate as a result of heat shock induction, we conclude that a subset of murine gamma delta T cells react to antigens on self cells in which a heat shock response was induced. PMID- 2106684 TI - Fractionation of heparin by chromatography on a tissue plasminogen activator Sepharose column. AB - Heparin stimulates the activity of tissue plasminogen activator (t-PA) and binds to t-PA. To study this interaction, a complex between t-PA and N-acetylated heparin was formed and then linked to Sepharose. This procedure selectively links the t-PA to the column because the acetylated heparin has no free amino groups. The procedure also protects the heparin-binding site(s) on the enzyme during coupling to the matrix. The t-PA column separates heparin into two fractions, one with low affinity for t-PA and one with high affinity. Both fractions of heparin effectively accelerate inactivation of thrombin by antithrombin III. However, the fractions differ in their ability to stimulate t-PA: the low-affinity heparin has no effect on the activity of t-PA, whereas the high-affinity heparin enhances this activity. These heparin fractions will be useful in characterizing the biochemical basis and physiological consequences of the heparin--t-PA interaction. PMID- 2106686 TI - Highly purified factor VIII concentrates. PMID- 2106685 TI - Sequencing of peptides and proteins with blocked N-terminal amino acids: N acetylserine or N-acetylthreonine. AB - Many proteins cannot be directly sequenced by Edman degradation because they have a blocked N-terminal residue. A method is presented for deblocking such proteins when the N-terminal residue is N-acetylserine (which occurs frequently in eukaryotic proteins) or N-acetylthreonine. The method has been applied successfully to the determination of the N-terminal amino acid sequence of human, bovine, and rat parathymosins. Prothymosin alpha and other blocked proteins and peptides were also readily deblocked and sequenced by this procedure. It is proposed that the mechanism of the deblocking reaction involves an acid-catalyzed N----O shift of the acetyl group followed by a beta-elimination. PMID- 2106687 TI - Plasma exchange donation of cryoprecipitate after DDAVP stimulation: an alternative source of factor VIII. AB - The last few paragraphs will summarize pertinent characteristics of this material in relation to other current sources of factor VIII. First, at a time when safety is the paramount concern in hemophilia therapy, plasma exchange donation offers a product with a very low intrinsic risk of blood borne infection; in many cases, this risk can be equivalent to a single unit of blood. This is much lower than previous versions of commercial factor VIII and much lower than the intrinsic risk of the starting material for current products. We believe this risk is low enough to justify its use without viral inactivation, although certain additional measures, such as the 6-month quarantine devised by Dr. Noel, could increase the margin of safety even further. Note that the principle of limitation of donor exposure is a proven one, which should be effective against any infectious agents, including those unknown to us at this time. Second, at a time when efforts to improve the safety of commercial factor VIII have led to extraordinary increases in cost, factor VIII from plasma exchange donation promises to be relatively inexpensive. Our data indicate that most blood centers could produce factor VIII in this way at 25-50% of the price of the newest commercial products. Finally, there is the matter of supply. At present, commercial factor VIII is in short supply. It may be that worldwide demand for other plasma derivatives, combined with the reduced yield of factor VIII associated with viral inactivation measures, will dictate chronic shortages for the forseeable future. In this unsettled milieu, plasma exchange donation offers a new source of factor VIII, which need not be tied to the supply of, or demand for any other plasma products. Instead, it depends on local initiatives in blood banks and hemophilia centers, and donor activity that can be tailored specifically to the needs of hemophilia patients. Thus, in spite of the impressive advances in the safety of commercial factor VIII which have recently been implemented, we believe there is a place for single donor cryoprecipitate from plasma exchange donation in the treatment of hemophilia and other bleeding disorders in the 1990's. Its use should be more widely and more extensively investigated. PMID- 2106688 TI - Diagnosis of von Willebrand disease. PMID- 2106689 TI - Use of DDAVP and cryoprecipitate in mild to moderate haemophilia A and von Willebrand's disease. AB - DDAVP has a major therapeutic role to play in the management of moderate to mild haemophilia and vWD, particularly type I. In addition it helps to classify vWD patients and to procure more and better blood products for treatment. The addition of suitable, reliable preparations for subcutaneous and intranasal use will enable early and follow-up treatment to be self-administered. The limiting features are that FVIII:C levels are not high enough or sustained long enough for some bleeding episodes and lytic activity may occasionally be clinically significant warranting simultaneous use of antifibrinolytic agents. Side effects are minimal but caution is needed in the very young and those with vascular disease. Cryoprecipitate remains the commonest source of normal multimeric VIII:vWF. The evaluation of procedures to decrease viral transmission is incomplete as is effectiveness of different preparations in correcting the BT in vWD. Wet cryo continues to be the product most likely to correct BT in severe vWD but laboratory tests better able to predict clinical haemostasis need to be developed. PMID- 2106690 TI - Management of von Willebrand's disease. PMID- 2106691 TI - Strategies to promote hemostasis in patients with F VIII inhibitors. PMID- 2106692 TI - The clinical use of porcine factor VIII. AB - Extensive worldwide experience with PE-fractionated porcine factor VIII concentrate has confirmed the expectation that the produce has an important place in the management of hemophiliacs with inhibitors, and that the problems which constrained the use of the original animal factor VIII concentrates have been largely overcome. A particular advantage, compared with PCCs and derivatives, is that dosage and effects can be monitored with conventional coagulation tests. PMID- 2106693 TI - Induction of immune tolerance with factor VIII concentrate in patients with hemophilia A and inhibitors. PMID- 2106694 TI - Induction of immune tolerance in hemophiliacs with inhibitors by combined treatment with i.v. IgG, cyclophosphamide and factor VIII or IX. PMID- 2106696 TI - Adaptation of the mammalian gas transport system to subterranean life. PMID- 2106695 TI - Gating of atrial muscarinic K+ channels by G proteins. PMID- 2106697 TI - Updated forecasts of the costs of medical care for persons with AIDS, 1989-93. AB - Data on the number of AIDS cases reported to the Centers for Disease Control (CDC) from January 1984 to June 1989 are used to predict the number of AIDS cases that will be diagnosed during the years 1989 through 1993. Using quadratic and linear models with the most recent data, it is projected that about 44,000 cases will be diagnosed in 1989, 56,000 in 1990, 70,000 in 1991, 87,000 in 1992, and 104,000 in 1993. These projections are lower than estimates derived using data from January 1984 to June 1988, and they are similar to estimates derived by the CDC. The lifetime medical care cost of treating a person with AIDS is estimated to be about $75,000 (all estimates are in 1988 dollars) assuming that the average length of survival is 15 months and that the intensity of care (that is, the cost of medical care per month) does not fall as longevity rises. This total, $75,000, reflects recent increases in the length of survival and the diffusion of costly drug therapies (for example, AZT and aerosol pentamidine). This study forecasts that the cumulative lifetime medical care costs of treating all people diagnosed with AIDS during a given year to be about $3.3 billion in 1989, $4.3 billion in 1990, $5.3 billion in 1991, $6.5 billion in 1992, and $7.8 billion in 1993. PMID- 2106698 TI - "Race-ethnicity": a dubious scientific concept. PMID- 2106699 TI - Community based AIDS treatment research centers to be established. PMID- 2106700 TI - State level expert review committees--are they protected? AB - Recently, the functioning of State-level expert review committees, operating under the auspices of professional medical societies, has become problematic. In particular, an increased number of State maternal mortality review committees have become inactive or disbanded primarily because of concern over liability of committee members and committee proceedings being used in litigation. A study was conducted of legal protection of the expert review process at the State level. The relevant immunity and privilege statutes of each State and the protection afforded by State law were analyzed. Findings show that, in all but a few States, the legal risk of participating in expert review is negligible. Most States have statutes that protect information involved in the review process from disclosure or use in subsequent litigation. Laws in most States also protect participants in the review process (both members of committees and providers of information) from civil liability. PMID- 2106701 TI - Report of a special panel on desired prenatal weight gains for underweight and normal weight women. AB - A major challenge facing the health care system is to improve the distribution of infant birth weights. Prenatal weight gain and prepregnancy weight status are two of the major factors that influence infant birth weight. These are independently and linearly related to birth weight. It is believed by many that the distribution of infant birth weights may be improved by implementing prenatal weight gain goals that optimize the relationship between prepregnancy weight status and infant birth weight. The panel considered prenatal weight gains for underweight and normal weight women that correspond to the delivery of infants with birth weights within a desired range. The panel identified (a) the desired range of birth weights as 3,500 to 3,999 grams; (b) for underweight women starting pregnancy, a prenatal weight gain of 30 to 35 pounds (lb), plus the prepregnancy weight deficit for the height of the woman; and (c) for normal weight women starting pregnancy, a gain of 30 to 35 lb. The report summarizes the scientific rationales for the conclusions, as well as the results of deliberations on potential risks to maternal health of the suggested weight gains. PMID- 2106703 TI - Estimating cancer mortality rates from SEER incidence and survival data. AB - A method to estimate site-specific cancer mortality rates using Surveillance, Epidemiology, and End Results (SEER) Program incidence and survival data is proposed, calculated, and validated. This measure, the life table-derived mortality rate (LTM), is the sum of the product of the probability of being alive at the beginning of an interval times the probability of dying of the cancer of interest during the interval times the annual age-adjusted incidence rate for each year that data have been collected. When the LTM is compared to death certificate mortality rates (DCM) for organ sites with no known misclassification problems, the LTM was within 10 percent of the death certificate rates for 13 of 14 organ sites. In the sites that have problems with the death certificate rates, there were major disagreements between the LTM and DCM. The LTM was systematically lower than the DCM for sites if there was overreporting on the death certificates, and the LTM was higher than the DCM for sites if there was underreporting. The limitations and applications of the LTM are detailed. PMID- 2106702 TI - Broadening the perspective of pica: literature review. AB - Pica is an eating disorder that is manifested by a craving for oral ingestion of a given substance that is unusual in kind and or quantity. It is a long-standing practice that has far reaching implications for prevention and treatment- implications for public health as well as clinical personnel who work in settings where they have the potential for influencing health knowledge, attitudes, and behaviors of their patients. Pica practices also challenge researchers and social scientists whose work encompass development and refinement of models related to nutritional deficiencies. The body of literature on pica is so fragmented that it is difficult to find a precise summary of the knowns and unknowns about the condition. There is little consistency in defining pica, classifying substances ingested, identifying key characteristics of practicers, recommending treatment, or in projecting outcomes. This review presents a framework for understanding pica as a general practice, summarizes divergent reported hypotheses and conclusions, and illustrates that there is a need for more comprehensive studies of prevalence and incidence and use of deductive as well as inductive research processes. PMID- 2106704 TI - Ischemic heart disease and hypertension: effect of disease coding on epidemiologic assessment. AB - During the changeover from the eighth to the ninth revision of the "International Classification of Diseases: Manual of the International Statistical Classification of Diseases, Injuries, and Causes of Death" (ICD), there were several major alterations of coding for the rubrics Ischemic Heart Disease (IHD) and Hypertension (HBP). As expected, these changes caused major discontinuities for IHD and HPB. These discontinuities were not, however, uniform over sex-race groups. When examined by component ICD codes, the discontinuities were found to vary in both magnitude and direction among the groups. In addition to discontinuity, there was a change in the rate of decline for IHD and HBP after the changeover. This rate of decline varied as well by sex-race group. In general, the decline among blacks was slower than among whites. Earlier studies that assessed IHD mortality have used different groupings of ICD codes to obviate the discontinuity, and researchers have observed a similar differential decline. These results should be viewed with caution because of the potential impact of differential coding on sex-race groups. As preparations are made for ICD-10, special attention should be given to the preservation of epidemiologic continuity to provide better assessment of trends in population subgroups. PMID- 2106705 TI - Efficacy of an intervention to promote use of hearing protection devices by firefighters. AB - Numerous cases of hearing loss consistent with noise-induced damage were noted among firefighters in the city of Columbia, MO. A survey of firefighting vehicles in operation showed that the firefighters were exposed to excessive noise levels and put at risk for noise-induced hearing loss (NIHL). Audiologic evaluation showed that 36 percent of the firefighters had moderate or severe hearing loss (a threshold of 40 decibels (dB) or more at 3,000, 4,000, or 6,000 hertz (Hz) in either ear). An educational program on NIHL was then carried out to increase the use of hearing protection devices (HPDs) by firefighters, followed by an evaluation of the intervention. The educational intervention successfully increased knowledge of NIHL, positive attitudes toward HPDs, and resulted in more frequent use of HPDs. After the intervention, 85 percent of firefighters regularly used HPDs compared with 20 percent before the intervention. Recommendations are made for fire departments to reduce the risk of NIHL. PMID- 2106706 TI - Career paths of geriatric nurse practitioners employed in nursing homes. AB - The career paths of geriatric nurse practitioners (GNPs) trained with support from the W. K. Kellogg Foundation through the Mountain States Health Corporation (MSHC) were studied. Under this program, GNPs were recruited from sponsoring nursing homes and returned to GNP positions in the sponsoring facilities following training. Training was carried out under a continuing education model offered through six university-based schools of nursing. Questionnaires were sent to the 111 GNPs trained. Of the 102 respondents, 97 provided complete information about past and present education, work experience, and job functions. The GNPs were women with a median age of 45 years, and they were employed in rural settings in the western United States. More than 45 percent of the nurses had at least a baccalaureate degree at the time of GNP training. The GNPs remained employed in long-term care positions that implemented the practitioner role. The median length of GNP employment in their first jobs after training was more than 4.5 years. The resignation rate from this first position was 1.66 resignations for each 10 years of GNP employment. Job changes were likely to be attributed to organizational changes with subsequent positions shifting toward a diversification of the GNP role. The study demonstrates the success of the MSHC program in introducing and retaining GNPs in nursing homes. PMID- 2106707 TI - Prevalence of Giardia lamblia and risk factors for infection among children attending day-care facilities in Denver. AB - A sample of children in the toddler age group was surveyed in Denver, CO, to determine the prevalence of Giardia lamblia and to identify risk factors for the intestinal disease. The sample consisted of 236 children attending day-care centers (DCC) and 79 who were not attending. Thirty-eight children (16 percent) attending DCCs and 7 (9 percent) who had not were positive for G. lamblia in stool samples. Risk factors for those attending DCC facilities included increasing duration of attendance, time per week attending DCCs, low family income, and large family size. The only risk factor for those not attending DCC facilities was travel to Colorado mountains. Multivariate analysis showed that risk factors for all children in the sample included travel to Colorado mountains, large family size, and attending DCC facilities. Infection was not associated with symptoms. PMID- 2106708 TI - Volunteer peer support therapy for abusive and neglectful families. AB - This project is designed to provide tertiary prevention services to physically abusive and physically neglectful families. The prevention service described, Volunteer Peer Support Therapy, is expected to significantly improve parenting skills and parents' expectations concerning their child, their knowledge about appropriate child behaviors, and coping strategies. The aim of the project is not only to intervene during crises, but also to improve the parent-child relationship on a long-term basis. In order to accomplish this goal, trained volunteers will be matched to the families being treated for physical abuse or physical neglect. The volunteers will be trained to take on roles traditionally performed by professional therapists and case managers. These roles include matching public and private services to the needs of the clients, investigating employment opportunities, and providing parenting role models. A second purpose of the project is to demonstrate the economic advantage of Volunteer Peer Support Therapy. To achieve that goal, a cost-effectiveness analysis will be performed. PMID- 2106709 TI - Operation Sunday School--educating caring hearts to be healthy hearts. AB - This project seeks to improve traditional hypertension screening of the black population by developing a community oriented approach that can increase knowledge and involve a new target group--black children--in preventive techniques. To help achieve the educational goals, an anti-hypertensive picture book for black children has been designed. The picture book will be distributed through church Sunday School classes. Several black churches in Chicago that were willing to host hypertension screenings for their congregations were identified; the picture books will be distributed through their Sunday School classes. Medical students, physicians, and members of the Black Nurses Association have been recruited to work collaboratively to introduce the picture book-manual, to instruct children on how to measure blood pressure, and to assist in the initial hypertension screenings at the churches. Funding is needed to print the manual and purchase sphygmomanometer sets for training. With the manual, equipment, and proper instruction of the children, each church will have the manpower to screen its at-risk population as often as possible. Educating black children about hypertension and its detection increases their awareness and provides them with the knowledge to screen adults. The success of this community support system is the exchange of knowledge between children and adults and the constant followup and preventive intervention supplied through a dominant community organization, the black church. PMID- 2106710 TI - A proposal for a foster grandmother intervention program to prevent child abuse. AB - The incidence of child abuse and neglect is epidemic. Many abused children have sustained lifelong injuries. Often they become perpetrators of abuse, continuing the cycle into future generations. Studies have indicated that mothers who are likely to abuse their children can be identified by a predictive method during the prenatal and postpartum periods. Pilot studies have indicated that mothers who are identified by the method and who receive early intervention, consisting of home visits by registered nurses, show a significantly lower rate of verified cases of child abuse. The author proposes a strategy for early intervention to prevent child abuse and neglect and to help infants and children attain their appropriate developmental milestones. The strategy calls for training and employing women from the Foster Grandparent Program. Foster grandmothers would be a valuable resource for high-risk mothers, providing role models for parenting skills in the home setting. Participating foster grandmothers would be trained and supervised in an interdisciplinary team setting. Evaluation of the program would compare the target population of infants and children whose mothers received the proposed intervention with a similar high-risk group that received only traditional interventions. PMID- 2106711 TI - Immediate effects of 14 non MAOI antidepressants in rats with spontaneous petit mal-like seizures. AB - 1. Wistar rats of a strain presenting spontaneous petit mal-like seizures were injected intraperitoneally with graded doses of 14 non-monoamine oxidase inhibitor antidepressants and the immediate effects on behavior and the EEG were recorded. 2. Amineptine and nomifensine, the two drugs interacting with dopaminergic neurotransmission, reduced the duration of spontaneous spike-wave discharges (SWD) and were thus potentially antiepileptic. 3. Trazodone increased SWD duration. 4. The antidepressants, imipramine-like (imipramine, chlorimipramine, desipramine, metapramine and amitriptyline) and non-imipraminic (minaprine, maprotiline, viloxazine, mianserin, fluvoxamine and indalpine), and the 3 noted above, had potentially convulsive effects. PMID- 2106713 TI - Effect of castration on eicosanoid and catecholamine-induced luteinizing hormone releasing hormone release in vitro. AB - The castration of adult rats four weeks before experimentation did not alter either the basal production of prostaglandin (PG) E2 (intact rats 1157 +/- 160 pg/mg protein, castrated rats 1093 +/- 90 pg/mg protein) or the A 23187-induced production of PGE2 (1591 +/- 209 or 1701 +/- 286 pg/mg protein respectively) or that of leucotriene (LT) C4 (474 +/- 33, 389 +/- 39 pg/mg protein). Castration significantly reduced the absolute amounts of luteinizing hormone-releasing hormone (LHRH) released under basal conditions (594 +/- 56 pg/mg protein to 34% of intact controls) and after A 23187 stimulation (to 28% of controls). The LHRH released by the median eminence (ME) of castrated rats in the presence of PGE2 (10(-6) M), LTC4 (10(-8) M), norepinephrine (NE) (10(-5) M) or dopamine (DA) (10( 5) M and 10(-4) M) was significantly lower than the LHRH released by intact animals in the presence of these factors. However the relative values for LHRH release (e.g. as % of controls) indicated that the degree of stimulation was identical in intact and castrated rats (2-3 times). These data suggest that the absence of gonadal steroids resulting from long-term castration does not block the stimulatory action of eicosanoids or catecholamines on the release of LHRH by the ME of adult male rats in vitro. Furthermore, castration does not interfere with the biosynthesis of PGE2 and LTC4. PMID- 2106712 TI - Mechanisms of platelet activating factor-induced aggregation and secretion in human platelets. AB - The role of TXA2 in PAF-induced aggregation and secretion of human platelets is unclear. We have studied the relationship between aggregation, synthesis of TXA2 and release of 5-HT during the time course of aggregation induced by PAF and collagen. For PAF-induced aggregation there was strong aggregation and secretion with minimal production of TXA2 in contrast to collagen in which a surge in TXA2 synthesis preceded both aggregation and secretion. To determine the role of calcium flux in PAF-induced aggregation we have similarly studied the temporal relationships between aggregation, secretion and TXA2 synthesis for calcium ionophore A23187 induced aggregation but found these to be distinctly different from those determined for PAF. A method for measuring absolute amounts of 5HT released from platelets in small volumes of plasma is described. We conclude that TXA2 is not important in the mechanism of PAF induced aggregation and that an increase in the level of intraplatelet calcium per se is not sufficient to explain the mediation of PAF-induced aggregation. PMID- 2106715 TI - Uteroplacental production of eicosanoids in ovine pregnancy. AB - Dramatic cardiovascular alterations occur during normal ovine pregnancy which may be associated with increased prostaglandin production, especially of uteroplacental origin. To study this, we examined (Exp 1) the relationships between cardiovascular alterations, e.g., the rise in uterine blood flow and fall in systemic vascular resistance, and arterial concentrations of prostaglandin metabolites (PGEM, PGFM and 6-keto-PGF1 alpha) in nonpregnant (n = 4) and pregnant (n = 8) ewes. To determine the potential utero-placental contribution of these eicosanoids in pregnancy, we also studied (Exp 2) the relationship between uterine blood flow and the uterine venous-arterial concentration differences of PGE2, PGF2 alpha, PGFM, 6-keto-PGF1 alpha, and TxB2 in twelve additional late pregnant ewes. Pregnancy was associated with a 37-fold increase in uterine blood flow and a proportionate (27-fold) fall in uterine vascular resistance (p less than 0.01). Arterial concentrations of PGEM were similar in nonpregnant and pregnant ewes (316 +/- 19 and 245 +/- 38 pg/ml), while levels of PGFM and PGI2 metabolite 6-keto-PGF1 alpha were elevated 23-fold (31 +/- 14 to 708 +/- 244 pg/ml) and 14-fold (12 +/- 4 to 163 +/- 78 pg/ml), respectively (p less than 0.01). Higher uterine venous versus uterine arterial concentrations were observed for PGE2 (397 +/- 36 and 293 +/- 22 pg/ml) and 6-keto-PGF1 alpha (269 +/- 32 and 204 +/- 32 pg/ml), p less than 0.05, but not PGF2 alpha or TxB2. Although PGFM concentrations appeared to be greater in uterine venous (1197 +/- 225 pg/ml) as compared to uterine arterial (738 +/- 150 pg/ml) plasma, this did not reach significance (0.05 less than p less than 0.1). In normal ovine pregnancy arterial levels of PGI2 are increased, which may in part reflect increased uteroplacental production. Moreover the gravid ovine uterus also appears to produce PGE2 and metabolize PGF2 alpha. PMID- 2106714 TI - Urinary excretion of prostacyclin and thromboxane metabolites in climacteric women: effect of estrogen-progestin replacement therapy. AB - To study the role of vasodilatory prostacyclin and vasoconstrictory thromboxane A2 in climacteric vascular instabilities, overnight urine samples were collected from sixteen women suffering from hot flushes and sweating before, during and after the six months' cyclic estradiol-desogestrel therapy as well as from ten non-climacteric control women. The urine was assayed for 6-keto-PGF1a and 2,3 dinor-6-keto-PGF1a (metabolites of prostacyclin) as well as for thromboxane B2 and 2,3-dinor-thromboxane B2 (metabolites of thromboxane A2) by means of HPLC and radioimmunoassay. No difference was seen in baseline prostaroid output between the climacteric and non-climacteric study groups. Furthermore, no relation was observed between individual prostanoid excretion and severity of vasomotor symptoms before replacement therapy. The replacement therapy abolished or markedly alleviated hot flushes and sweating, but prostanoid output did not change. Our data imply that climacteric symptoms are not accompanied by changes in the production of prostacyclin and thromboxane A2. PMID- 2106716 TI - Thromboxane synthase inhibition: "endoperoxide shunt phenomenon" does not occur in healthy humans in vivo. AB - The effects of the thromboxane synthase inhibitor CGS13080 on the in vivo synthesis of thromboxane and prostacyclin were determined in six healthy volunteers. Two different doses (0.08 and 0.25 mg/kg x h) were infused for six hours under strictly controlled conditions and 2,3-dinor-TxB2 and 2,3-dinor-6 keto-PGF1 alpha were measured in urine using gaschromatography--mass spectrometry. The in vivo synthesis of thromboxane was inhibited by 80-75% while there was no effect on the in vivo prostacyclin synthesis. PMID- 2106717 TI - Control of expiratory duration by arterial CO2 oscillations in vagotomized dogs. AB - The role of respiratory oscillations of PaCO2 (CO2 oscillations) in the regulation of expiratory duration (TE) was examined in eight anesthetized dogs by measuring instantaneous changes of arterial pH during the respiratory cycle with a catheter-tip ISFET (ion-sensitive field effect transistor) pH electrode. Steady state changes in arterial pH oscillation were induced by vagotomy, which increased the amplitude of pH oscillation from 0.014 +/- 0.002 (mean +/- SEM) to 0.058 +/- 0.006 units (P less than 0.001), and prolonged TE from 5.12 +/- 0.56 to 9.99 +/- 1.11 sec (P less than 0.005) with little change in average pH (0.021 +/- 0.011 units, P = 0.12). Vagotomy also reversed the phase relationship between arterial pH oscillation at the carotid bodies and tidal ventilation, such that pH rose during early expiration, rather than falling as occurred in the intact state. When the within-breath oscillation of arterial pH was transiently reduced by having the vagotomized dogs inspire a single breath of CO2 enriched air, TE of the same breath was shortened in proportion to the reduction in amplitude of pH oscillation (r = 0.72, P less than 0.001), rather than in proportion to changes in the average pH of the test breath (r = 0.44). The results indicate that the profile of within-breath oscillation of PaCO2 (phase relationship and amplitude) can exert an important influence on TE, and may in part account for the prolongation of TE following vagotomy. PMID- 2106718 TI - The effect of pH and hypoxia on function and intracellular pH of the rat diaphragm. AB - We studied the relationship between contractile function and intracellular pH (pHi) in the isolated rat diaphragm when superfusate PCO2 was changed during hyperoxia or hypoxia. Superfused diaphragm strips were field stimulated at 0.5 Herz, and twitch tension (TT) was recorded. The pHi was calculated from the volume distribution of a weak acid, dimethyl-oxazolidinedione. In hyperoxia, hypercapnic acidosis (pH 7.06-6.63) depressed diaphragm pHi and TT, whereas hypocapnic alkalosis (pH 7.82-8.15) increased pHi but did not significantly affect TT. TT was maximum at physiological pHi (7.06), but in hyperoxic hypercapnic muscles substantial force was still generated at pHi values as low as 6.44. Hypoxia (PO2 30-38 mm Hg) markedly reduced TT; this effect was slightly exacerbated by hypercapnia and attenuated by hypocapnia. Hypoxia lowered pHi by about 0.2 units, which was insufficient to account for the hypoxic contractile failure. Knowledge of the hyperoxic muscle TT/pHi relationship suggests that, in other contexts, caution should be exercised in attributing severe muscle fatigue or force loss to modest falls in pHi. PMID- 2106719 TI - Bumetanide and cerebrospinal fluid acid-base variables during acute CO2 elevation. AB - The purpose of this study was to investigate the effects of bumetanide, an inhibitor of NaCl cotransport on cisternal cerebral spinal fluid (CSF) acid-base balance during acute respiratory acidosis (ARA). We measured blood and CSF acid base variables in two groups (N = 7 in each) of anesthetized paralyzed and mechanically ventilated dogs with bilateral ligation of renal pedicles (to eliminate saluresis). After baseline samples were obtained (-1 h) bumetanide (0.5 mg/kg) was administered intravenously within 15 min (group 2); group 1 received equal volume of diluted saline. ARA was induced 1 h later (0 h) and was maintained for 5 h. In both groups PaCO2 was maintained between 55 to 60 mm Hg. Mean cisternal CSF PCO2 was 42.8 +/- 2.6, and 43.8 +/- 2.5 mm Hg, respectively in group 1 and group 2 and rose approximately 20 mm Hg during ARA. In group 1, CSF [HCO3-] was 22.0 +/- 1.0, 24.8 +/- 0.6, and 25.4 +/- 1.6 mEq/L, respectively at 0, 2 1/2, and 5 h; respective values for group 2 were 22.9 +/- 1.5, 24.7 +/- 1.4, and 26.1 +/- 1.3 mEq/L. Comparing the two groups, respective values were not significantly different from each other. Similarly, between the two groups changes in CSF [Na(+)-Cl-] during ARA were not significantly different from each other. Based on our results we conclude that at the dose used in the present study bumetanide does not change ionic composition and acid-base balance of cisternal CSF when compared to controls. Because changes in CSF [Na(+)-Cl-] during ARA were similar in both groups, any inhibition of Cl- influx into CSF by bumetanide should have been proportional to that of Na+. PMID- 2106720 TI - [Parkinson disease and photosensitive epilepsy]. AB - A 58 year-old man with a 4-year history of Parkinson's disease developed a myoclonic syndrome with photosensitivity. The photo-convulsive response progressively worsened when therapy with levodopa, carbidopa and biperiden was interrupted. A marked reduction of the photosensitivity was obtained with bromocriptine. This case suggests that both diseases are correlated with a multiple degenerative process of the dopaminergic inhibitory pathways. PMID- 2106721 TI - [Inhibin]. PMID- 2106722 TI - The immunologist and the developing world. PMID- 2106723 TI - Tumour necrosis factor in hepatosplenic schistosomiasis. AB - Periportal fibroplasia is the dominating feature of hepatosplenic schistosomiasis. Since monokines play an important role in the regulation of fibroplasia, tumour necrosis factor (TNF) and interleukin 1 beta (IL-1 beta) were assessed in sera and cell culture supernatants from patients with intestinal and hepatosplenic schistosomiasis before and 3-6 months after treatment with praziquantel. Uninfected controls were from the study area in Alagoas, Brazil. TNF was measured using an L-M mouse fibroblast bioassay and radioimmunoassays specific for TNF-alpha. Whereas TNF-alpha was elevated threefold in the patients' sera, three- to five-fold reductions of TNF were observed by radioimmunoassay and bioassay, respectively, in cell culture supernatants of hepatosplenic schistosomiasis patients. Significant deviations, in opposite directions, from TNF levels in control sera and supernatants are most plausible in the event of a sequestration of TNF-alpha-producing cells from the circulation. This process may be disease stage-specific since a dichotomy between incipient and advanced cases of hepatosplenic schistosomiasis became apparent in the amplitude and kinetics of changes during the follow-up after treatment. PMID- 2106724 TI - Lack of the G2m(n) allotype in IgG subclass deficiency, in IgG2 deficiency together with lack of G1m(a) and G3m(g), and in IgG3 deficiency together with lack of G1m(f) and G3m(b). AB - Lack of G2m(n) was demonstrated in both IgG2-deficient and IgG3-deficient Caucasian patients. Lack of G2m(n) or G2m(",") was found together with homozygosity for both G1m and G3m allotypes as the dominant finding, i.e. for IgG2-deficient patients together with G1m (f,f) and G3m(b,b), constituting the Gm(f,",b) phenotype, and for IgG3-deficient patients together with G1m(a,a) and G3m(g,g), constituting the Gm(a,",g) phenotype. The group with IgG2 deficiency and the selected patients with the Gm(f,",b) phenotype expressed characteristically very low or undetectable IgG4, significantly increased IgG3, and normal IgG1. The group with IgG3 deficiency and the selected patients with the phenotype Gm(a,",g) expressed instead normal IgG4 and nearly normal IgG2 and IgG1 levels. The lack of G2m(n) together with lack of one or the other of the alternative G1m genes and corresponding G3m genes give different IgG2 levels and different IgG subclass patterns. The frequency of G1m allotypes and corresponding G3m allotypes also deviated significantly when the IgG2 deficiency and IgG3 deficiency groups were compared with each other. Most IgG subclass-deficient patients are homozygous in the Gm system and lack genetic variants in the three IgG subclasses, IgG1, IgG2, and IgG3. PMID- 2106725 TI - [Prenatal care in at-risk pregnancies]. AB - Systematic development of prenatal care is a significant factor in the reduction of maternal and perinatal morbidity and mortality. Despite impressive advances in prenatal and perinatal care, attempts at prevention for most serious pregnancy complications are limited by the lack of sensitive and specific indicators allowing prediction with any degree of probability. In view of the widening spectrum of methods for the diagnosis of pregnancy complications, the dangers of broad application without a critical benefit/risk analysis must be stressed. Apart from rising costs, the effect on pregnant women in terms of increased anxiety must be borne in mind. For the majority of women the core or prenatal care must remain conventional clinical examination combined with extensive consultation and information. Repeated use of technology such as ultrasound, Doppler, cardiotocography etc. should be limited to pregnancies with high risk of serious complications. Invasive preventive measures such as hospitalization, cerclage or administration of tocolytic drugs also need critical use and should be confined to a limited number of genuine high risk cases. PMID- 2106726 TI - On the DNA polymerase-a mutant: immunofluorescence assay of UV-induced thymidine dimers in Aphr-4-2 cells. AB - Aphidicolin inhibits purified DNA polymerases-a and -d in vitro and inhibits mitosis in animal cells. The Chinese hamster V79 cell mutant, Aphr-4-2, was selected for its ability to form colonies in cultured medium supplemented with 1.0 microM aphidicolin. At this concentration, the parental wild-type V79 cells (clone 743x) have a survival rate of less than 10(-7). The mutant DNA polymerase a is resistant to aphidicolin at concentrations that are inhibitory to the wild type V79 DNA polymerase-a. The apparent Km for dCTP of the mutant DNA polymerase a is consistently lower than that of the wild-type DNA polymerase-a. This mutant exhibits slow growth, mutator activity, hypersensitivity, and hypermutability to UV. We wanted to know the basis of UV hypersensitivity in this mutant. Using the antisera (UV2) raised against UV-induced thymidine dimers and a sensitive immunofluorescence assay to measure UV-induced thymidine dimers and with detection in ACAS 570 Workstation, we observed that 50% of the thymidine dimers disappeared within 5 h after irradiation and more than 80% of the dimers were removed within 24 h in both cell lines. These results indicate that the recognition, incision, and excision steps in nucleotide excision repair pathway are normal in the mutant. In order to know if there is a difference in DNA polymerase-a or -d activities in the parental V79(wt) and Aphr-4-2 cells, DNA polymerases were partially purified from the parental and the mutant cells using sequential centrifugation and column chromatographies on DEAE-cellulose (DE23 and DE52) to remove DNA polymerases-beta and -gamma. More than 90% of the enzymatic activities from both cells showed characteristics of DNA polymerase-a type on the basis of these criteria: sensitivity to butyl phenyl dGTP (1 microM) and to IgG raised against DNA polymerase-a (SJK 132-20). The results indicate that DNA replication involving a mutant DNA polymerase-a with altered affinity for dCTP may be responsible for the UV sensitivity and mutability of the mutant. PMID- 2106727 TI - Recent advances in the surgical treatment of the short-bowel syndrome. PMID- 2106728 TI - Nutrition and cancer in children. AB - The information generated to date regarding the nutritional status of children with cancer indicates that malnutrition is seen in patients in the later stages of their malignant disease or is iatrogenic because of their intensive therapy. Malnourished children suffer from inadequate growth, including the potential of delayed cerebral development, and they are more susceptible to infection. Nutritional therapy has been shown to reverse the malnutrition independent of the cancer treatment. In doing so, the nutritional support aids in the delivery of and tolerance to the antitumor therapy. What is not possible, however, is making ineffective or marginally effective anticancer therapies effective by nutritional support. Therapy that is ineffective, such as chemotherapy for Stage III or IV neuroblastoma in children, cannot be altered by nutritional support. However, a patient's nutritional state may affect the disease outcome in that complication rates are much higher in malnourished patients. In such children with PCM, nutritional support may make delivery of therapy possible, but it will not affect the ultimate disease outcome unless the anticancer therapy is inherently successful. A well-nourished child is easier to treat and is physiologically more stable. Such children, therefore, have an improved prognosis and lower morbidity and mortality, provided effective therapy is available for the cancer. PMID- 2106729 TI - Diagnosis-related groups, route of admission, age and outcome for general surgical patients. PMID- 2106730 TI - Extracorporeal removal of anticancer drugs in hepatic artery infusion: the effect of direct hemoperfusion combined with venovenous bypass. AB - The effect of a new extracorporeal system combining direct hemoperfusion (DHP) with venovenous bypass was evaluated in the elimination of anticancer drugs in hepatic artery infusion. Adriamycin (3 mg/kg) and mitomycin C (1 mg/kg) were given to mongrel dogs through the hepatic artery with three different durations of 1, 10, and 20 minutes. Plasma drug levels were determined at the inlet and outlet of DHP and right external jugular vein (systemic level). Blood flow through DHP averaged 200 ml/min. In dogs without DHP (group I; n = 4), systemic levels of adriamycin and mitomycin C increased rapidly with 1-minute infusion, reaching the peak values of 6.61 +/- 2.44 (mean +/- SD) and 2.20 +/- 1.05 micrograms/ml, respectively. With DHP under single venous bypass (group II; n = 5), the peak values were reduced to 1.25 +/- 1.02 and 0.79 +/- 0.52 microgram/ml. Moreover, the peak levels were markedly reduced by DHP under hepatic venous isolation (group III; n = 6), the values being 0.41 +/- 0.15 and 0.13 +/- 0.07 microgram/ml with 1-minute infusion. The drug-removal rates were improved substantially in group III compared with group II. The longer the duration of infusion, the higher the removal rates tended to be in group III. These results indicate that effective elimination of anticancer drugs can be accomplished by this system during intraarterial chemotherapy of the liver. PMID- 2106731 TI - Usefulness of valproate sodium for treatment of incontinence after ileoanal anastomosis. AB - We report on the excitatory effect of gamma-aminobutyric acid, which increased after the oral administration of valproate sodium, on anal canal resting pressure in human beings, gamma-aminobutyric acid receptors. We used this drug in order to improve continence after ileoanal anastomosis. Seventeen patients (eight with ulcerative colitis and nine with adenomatosis coli) were tested after receiving ileoanal anastomosis. The placebo showed no effect, but valproate sodium could ameliorate frequent defecation and soiling and the resulting perianal skin complications. Increasing anal resting pressure was also observed during valproate sodium administration without the amplitude, frequency of peristaltic wave, or voluntary squeeze pressure being affected. These results suggest that the subchronic administration of valproate sodium may be useful in the treatment of minor incontinence after ileoanal anastomosis. PMID- 2106732 TI - Single-dose antibiotic prophylaxis in patients at high risk for infection in biliary surgery: a prospective and randomized study comparing cefonicid with mezlocillin. AB - The usefulness of antibiotic prophylaxis in biliary surgery is well established. When antibiotic prophylaxis is not used, wound infection rates after biliary surgery range from 10% to 25%. With antibiotic prophylaxis, the rates can be reduced to less than 5%. Three questions are still controversial: Do all patients undergoing biliary surgery require antibiotic prophylaxis? What is the ideal antibiotic for use in biliary surgery? What should be the duration of antibiotic prophylaxis? In this study we prospectively evaluated the efficacy of a single dose of antibiotic prophylaxis in biliary surgery, administered to patients at high risk for infection, in a trial comparing cefonicid (a cephalosporin with a long half-life) with mezlocillin (a broad-spectrum ureidopenicillin). PMID- 2106733 TI - [Hormone treatment of prostatic cancer]. PMID- 2106734 TI - European versus North American cardioplegia: comparison of Bretschneider's and Roe's cardioplegic solutions in a canine model of cardiopulmonary bypass. AB - Roe's and Bretschneider's crystalloid cardioplegic solutions were compared in a canine model of total cardiopulmonary bypass with 4.5 hours of hypothermic (27 degrees C) ischemic arrest and 60 minutes of reperfusion. Bretschneider's solution (Group I, six dogs) preserved tissue adenosine triphosphate (ATP) near control levels and maintained coronary effluent pH near 7.0 throughout the ischemic interval, while Roe's solution (Group II, six dogs) allowed progressive acidosis and depletion of ATP (P less than 0.005 versus control). Group I had supranormal left ventricular function during reperfusion (greater than 100% of pre-arrest function) but Group II regained only 40-75% of pre-arrest function. Group I had 2.82% +/- 3.61% necrosis of heart mass and Group II 9.33% +/- 8.26 (P less than 0.10). We conclude that Bretschneider's solution provided better myocardial protection than Roe's solution. The development of acidosis in the Roe group suggests that the more effective buffering of Bretschneider's solution with histidine is the probable basis for its superiority. PMID- 2106735 TI - Clinical evaluation of hypothermic ventricular fibrillation, multi-dose blood cardioplegia, and single-dose Bretschneider cardioplegia in coronary surgery. AB - 37 patients undergoing coronary revascularization were randomly assigned to three protocols for intraoperative myocardial protection: hypothermic ventricular fibrillation (HF) (n = 13), multi-dose blood cardioplegia (BCP) (n = 12) and single-dose Bretschneider's crystalloid cardioplegia (CCP) (n = 12). As intraoperative markers of ischemic damage myocardial ultrastructure, ATP, and CP contents were determined in left ventricular biopsy specimens taken before and after cardiac arrest. Release of serum enzymes (CK, CK-MB, LDH, SGOT) was determined pre- and postoperatively. Hemodynamic data were assessed before, during, and after operation. The incidence of low cardiac output, positive inotropic support, intraaortic balloon counterpulsation, peri-operative myocardial infarction, rhythm disturbances, and the rate of spontaneous defibrillation was compared between groups. The results show a better preservation of high energy phosphates in the BCP group as compared to the HF and CCP groups. Myocardial ultrastructure showed moderate ischemic damage in the hypothermic fibrillation group; in contrast, only slightly deteriorated cells were seen after cardiac arrest, when cardioplegia was used. The incidence of rhythm disturbances was 25% for HF and 42% for CCP. In contrast, only 17% of new rhythm disturbances were seen in the BCP group. Functional recovery (i.e. CI and SWI) of hearts protected with BCP was generally greater as compared to HF and CCP. Release of MB-creatine-kinase isoenzyme was higher in the HF group as compared to cardioplegia. Clinical outcome in terms of incidence of peri operative infarction, positive inotropic support and low cardiac output was superior in the BCP group but not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106736 TI - Effect of plasma glucose concentration on cerebral metabolism during partial ischemia in neonatal piglets. AB - We used neonatal piglets to determine the influence of plasma glucose concentration on cerebral energy metabolism during and immediately after partial ischemia. We assessed cerebral metabolism using in vivo phosphorus-31 magnetic resonance spectroscopy. Arterial plasma glucose concentration was increased in four piglets by systemic infusions of dextrose in water for comparison with infusions of saline in four controls or decreased in eight piglets by fasting for 24-48 hours for comparison with four fed piglets. Plasma glucose concentration showed a significant linear correlation with intracellular pH (r = -0.7, p less than 0.05). Piglets that developed hypoglycemia during partial ischemia had a smaller reduction in intracellular pH and a larger increase in inorganic phosphate content than piglets that were normoglycemic or hyperglycemic during ischemia. Similar differences persisted during the first 5 minutes of postischemic reperfusion. Subsequently, the cerebral concentrations of phosphorylated compounds returned to normal in all piglets. Our results demonstrate that 1) arterial plasma glucose concentration influences cerebral energy metabolism and intracellular pH during ischemia, 2) neonatal piglets can develop profound brain acidosis, and 3) brain acidosis during ischemia does not influence the restoration of cerebral phosphorylated compounds to control levels during the first 90 minutes after ischemia. PMID- 2106737 TI - Protein kinase C is crucial in signal transduction during interferon-gamma induction in endothelial cells. PMID- 2106738 TI - Orthoclone OKT3 as rescue treatment for steroid-resistant and recurrent acute rejection in clinical renal transplantation. PMID- 2106739 TI - Orthoclone OKT3 as first-line therapy in acute renal allograft rejection. PMID- 2106740 TI - First and second course of OKT3 monoclonal anti-T cell antibody for treatment of renal allograft rejection followed by testing for anti-OKT3 IgM and/or IgG immunization. PMID- 2106741 TI - OKT3 prophylaxis in liver transplantation: the Scandinavian experience. PMID- 2106742 TI - Acute graft-versus-host disease and slow marrow recovery after transplantation of OKT8-positive T cell-depleted marrow from an HLA mismatched related donor. Kanazawa Bone Marrow Transplantation Team. PMID- 2106743 TI - [Infections caused by Branhamella catarrhalis]. AB - Branhamella catarrhalis, formerly Neisseria catarrhalis, is a common bacteriological finding in the upper respiratory tract in infancy, and it ranks third on the list of bacterial causes of otitis media and sinusitis. In adults Branhamella catarrhalis may cause acute exacerbations of bronchitis and pneumonia, especially in patients with chronic lung disease. Branhamella catarrhalis is being recognized more frequently as a nosocomial pathogen and it may cause septicaemia in immunocompromised patients. Resistance to penicillin is prevalent and is due to production of beta-lactamases. The pathogenic potential of this agent should not be overlooked. PMID- 2106744 TI - [Fatal catheter septicemia with finding of Candida lusitaniae]. AB - A case of lethal pulmonary infection after catheter septicaemia with demonstration of C. lusitaniae in the blood is reported in a 73 year old patient with terminal Crohn's disease receiving long-term parenteral nutrition. PMID- 2106745 TI - Microcystin-LR-induced ultrastructural changes in rats. AB - The ultrastructure of hepatic, pulmonary, and renal lesions was evaluated in rats injected intraperitoneally with a lethal dose of microcystin-LR (MCLR, 160 micrograms/kg), a cyclic heptapeptide hepatotoxin produced by the blue-green algae, Microcystis aeruginosa. Hepatic lesions were first seen at 10 minutes post dosing and consisted of mild widening of hepatocyte intercellular spaces centrilobularly. At 20 minutes post-dosing, hepatocyte plasma membrane alterations were more pronounced, consisting of plasma membrane invagination with formation of variably sized and shaped intracytoplasmic vacuoles, loss of microvilli along the sinusoidal face, and widespread, pronounced hepatocyte separation. By 30 minutes, the space of Disse was markedly widened. At 60 minutes post-dosing, centrilobular areas contained necrotic cells and apparently intact, isolated, organelles intermingled with erythrocytes and platelets. In less severely affected regions there was prominent hepatocyte rounding, and erythrocytes and platelets were present in the widened space of Disse. Large amounts of hepatocellular debris and intact hepatocytes were present in the pulmonary vasculature, while smaller amounts of debris were also seen in the glomerular and peritubular capillaries of the renal cortex. This study shows that initial lesions are confined to shape changes in the plasma membrane of hepatocytes. These changes are consistent with the hypothesis that microcystin-LR induces alterations in the hepatocyte cytoskeleton. Later changes consist of hepatocyte disassociation and necrosis, as well as endothelial damage, which allow release of hepatocytes and debris into the circulation with microembolism in lungs and kidneys. PMID- 2106746 TI - Spindle cell reaction to nontuberculous mycobacteriosis in AIDS mimicking a spindle cell neoplasm. Evidence for dual histiocytic and fibroblast-like characteristics of spindle cells. AB - We report 5 patients with AIDS who had an unusual spindle cell proliferation in the lymph nodes and skin caused by nontuberculous mycobacteriosis. The spindle cell proliferation in these tissues may mimic a spindle cell neoplasm and pose a diagnostic problem if an infectious aetiology is not suspected. The fibroblast like spindle cells contained numerous acid fast bacilli. They were strongly positive for antibody markers of monocyte/macrophage and leukocyte derivation: Leu M3, Mo-9, T-200, and HLA-DR, and variably positive for alpha-1 anti chymotrypsin and lysozyme. Ultrastructurally these spindle cells were predominantly fibroblast-like with poorly developed features of macrophages. These results reveal the dual macrophage and fibroblastic character of the spindle cells and probably imply a functional differentiation rather than a histogenetic one. PMID- 2106747 TI - Basement membrane changes in atrophic tubules in the human kidney. AB - Changes in the basement membrane (BM) in atrophic tubules in human kidney biopsies were studied by electron microscopy and by immunohistochemistry on cryostat sections with antibodies against collagen type I, type III, type IV, laminin, EMA, keratin and vimentin. The BM showed different degrees of thickening with formation of reduplications which contained fibrocytes. Remnants of cytoplasm of epithelial cells and fibrocytes were incorporated in the thickened BM. This showed signs of lysis and disintegration, indicating that the redundant BM formed by the epithelial cells is removed, although imperfectly, by interstitial cells. Thinning of the BM was another frequent finding. Immunohistochemistry showed a clear reactivity for collagen type IV and laminin in all BM material. The epithelial cells showed multilayering and a peculiar type of dark cells extending underneath adjacent cells and separating them from their BM attachment. PMID- 2106748 TI - The surface to volume ratio of mitochondria, a suitable parameter for evaluating mitochondrial swelling. Correlations during the course of myocardial global ischaemia. AB - Cellular changes occurring in the left ventricular myocardium during ischaemia after different methods of cardiac arrest have been evaluated by morphological and morphometric parameters: volume densities of mitochondria (VVMi), sarcoplasm (VVSp), myofibrils (VVMf), surface densities of mitochondria (SVMi). The surface to volume ratio of mitochondria (SVratioMi) has been used as an independent parameter of mitochondrial swelling. Since ischaemic swelling of myocardial cells increases the volume of the reference space and ischaemic swelling of mitochondria decreases the free sarcoplasm, VVMi and VVSp cannot be considered as reliable indicators of the degree of oedema. SVMi/VVMf remains nearly constant after different forms of cardiac arrest, demonstrating the integrity of mitochondrial outer membranes. The inverse linear ratio between SVratioMi and the mean mitochondrial volume indicates that the increase in mitochondrial volume is achieved by surface smoothing. Loss of matrix structure and fragmentation of cristae occur at an SVratioMi of about 5.8, cristolysis at 5.5 to 5.6 and amorphous matrix densities at an SVratioMi of less than 5.5 micron2/micron3. The SVratioMi is a suitable parameter for evaluating mitochondrial swelling both at the onset and during global myocardial ischaemia, independent of the method of cardiac arrest used. It serves as an indicator of the state of structural preservation of mitochondria during ischaemia. PMID- 2106749 TI - Ultrastructural effects induced by global ischaemia on the AV node compared with the working myocardium. A qualitative and morphometric investigation on the canine heart. AB - The cardiac conduction system is considered to be particularly resistant to ischaemia. Nevertheless, following open heart surgery with short periods of ischaemia disturbances in AV conduction or ventricular arrhythmia have been reported. We compared the ultrastructure of AV node and working myocardium following 30 min global ischaemia at 25 degrees C, during pure ischaemia and with HTK cardioplegia qualitatively and morphometrically. After 30 min of pure ischaemia, interstitial and intracellular oedema together with considerable changes in organelles in AV nodes predominate over mainly cellular oedema in working myocardium. Sometimes irregular overcontractions of sarcomeres occur in the AV node, though very seldom in working myocardium. In pure ischaemia, mitochondrial swelling is comparable in both types of tissue. Following HTK cardioplegia and 30 min ischaemia, cellular oedema and mitochondrial swelling are significantly reduced in AV nodal cells and working myocardium, but remain more extensive in the AV nodes. Irregularities in the contractile state of sarcomeres are not observed. The extent of the ultrastructural alterations corresponds to the degree of metabolic change in the working myocardium. Thus, despite considerable differences during pure ischaemia and HTK cardioplegia, ultrastructurally the AV nodal cells do not display a greater resistance to ischaemia than working myocardium. PMID- 2106750 TI - Amyloid in intervertebral discs of surgery and autopsy material. A new class of amyloid? AB - Intervertebral discs from 82 consecutive operations on herniation and 59 autopsies (one case with generalized amyloidosis) were studied. Amyloid deposits observed in surgical and autopsy specimens increased with age in both series. Degenerative changes were related to age and to amyloid deposits in autopsy, but not in surgical cases. Calcium pyrophosphate dihydrate deposits (often in proximity to amyloid deposits) were found in autopsy discs of six patients and in surgical specimens of three patients with previous operations on herniated discs. Antisera against amyloid fibril proteins of different types including AA-, A lambda-, A kappa, AF- and AB-types showed no reaction with disc amyloid. In one case with generalized A lambda-amyloidosis the disc amyloid was not of the A lambda-type. Based on our results, we suppose that disc amyloid is a form of localized senile amyloidosis - possibly representing a new class of amyloid limited to cartilage tissue. PMID- 2106751 TI - Expression of epidermal growth factor receptor in normal colorectal mucosa, adenoma, and carcinoma. AB - Using the monoclonal antibody EGF-R1, the expression of epidermal growth factor receptor (EGFR) was investigated immunohistochemically in normal colonic mucosa distant from and adjacent to colonic neoplasms, in 25 adenomas and in 144 unselected colorectal carcinomas. EGFR expression was an inconsistent phenomenon in each of these conditions. It was not expressed in 23/44 non-neoplastic mucosa specimens distant from and in 26/44 mucosae adjacent to colon tumours; 15/25 adenomas and 71 (49.3%) of the carcinomas failed to contain detectable amounts of EGFR. In contrast, large amounts of EGFR were found in 4 non-neoplastic mucosae at both locations, in 3 adenomas and in 11 (7.6%) carcinomas. The remaining cases showed complex patterns of EGFR-expression. In comparing mucosae close to and distant from a colonic tumour, only minor differences in EGFR content were observed. The intra-individual comparison of the mode of EGFR expression in non neoplastic and neoplastic epithelium revealed an overexpression of EGFR in carcinomas in about one third of the 44 cases examined. One third showed no obvious differences, and one third showed lower levels of EGFR expression within the tumour. We conclude that the mode of EGFR expression in normal and neoplastic colon epithelium is variable and reflective of inter-individual constitutive differences rather than of abnormalities in gene regulation. Statistical analysis failed to reveal correlations between the mode of EGFR expression and tumour grade, type or Dukes stage. PMID- 2106752 TI - Immunohistochemical differential diagnosis of granulocytic sarcomas and malignant lymphomas on formalin-fixed material. AB - A panel of monoclonal antibodies (anti-CD45 [common leukocyte antigen], Ki-B3, L26, MT1, UCHL1, anti-CD15 [X-hapten], anti-neutrophil granule protein elastase [NP57]), anti-lysozyme, and the naphthol-ASD-chloroacetate reaction were applied to two cases of granulocytic sarcoma (GS) for evaluation of their utility in differentiating GS from malignant lymphoma. Lysozyme and naphthol-ASD chloroacetate esterase were found to be the most reliable markers for detection of the myeloid nature of the tumour cells. GS infiltrated solely the mucosa of the nasal cavity in one case, while in the other it involved both the nasal cavity and maxillary sinus with simultaneous eruptions on the skin of the trunk. In both cases, peripheral blood and bone marrow findings were inconspicuous at the time of diagnosis of GS. PMID- 2106753 TI - Subclinical course of cholesterol ester storage disease (CESD) diagnosed in adulthood. Report on two cases with remarks on the nature of the liver storage process. AB - An extremely benign variant of cholesterol ester storage disease (CESD) was diagnosed in two female patients aged 43 and 56 years. In one of them the course was entirely subclinical until a stroke at the age of 47, most probably a complication of secondary hyperlipoproteinaemia. The diagnosis was made accidentally in vivo during extensive examination for concomitant monoclonal gammapathy. The other patient (aged 56), still displays a fairly stable course with minor dyspeptic symptoms. The clinical findings in both patients were confined to moderate well tolerated hepatomegaly, hyperlipoproteinaemia of IIb type and xanthelasmata. Acid lipase activity was markedly deficient in peripheral leukocytes and cultured fibroblasts. These cases represent a rare adult variant the existence of which should be borne in mind in the differential diagnosis of chronic liver disease in advanced age and of hyperlipoproteinaemic states. The diagnostic criteria for the routine clinicopathological steps are summarized with emphasis on a special lipopigment deposition pattern, encompassing inhibition and modification of lipofuscin generation in hepatocytes and an excess of ceroid production in both portal and intralobular histiocytes. The varied ultrastructural appearance of the lysosomal limiting membrane complex is described. PMID- 2106754 TI - Diffuse sclerosing variant of papillary thyroid carcinoma. S-100 protein immunocytochemistry and prognosis. AB - The recently published second edition of the WHO classification of thyroid tumours describes the diffuse sclerosing papillary carcinoma (DSPC) as a specific variant of papillary thyroid cancer (PC). Besides several histological hallmarks, this rare tumour is characterized by its occurrence in young individuals and is thought to have a less favourable prognosis than PC in general. The observations on two examples of this tumour presented herein, however, are at variance at this assumption. The neoplasms occurred in a 10 year old girl and a 34 year old woman. Each time, diffuse involvement of both thyroid lobes and bilateral cervical lymphadenopathy were seen. In one case, the carcinoma extended into the cervical soft tissue. Follow-up disclosed both patients to be without evidence of disease 2 and 13 years, respectively, after thyroid surgery. Immunocytochemically, both thyroid primaries as well as 7 other cases of DSPC reported in the literature showed dense accumulations of S-100 protein positive dendritic/Langerhans cells. Such infiltrations have been demonstrated to be correlated with a benign clinical course of PC. It is thus suggested that DSPC behaves similarly or even less aggressively than PC in general, at least if prominent Langerhans cell infiltration is present. PMID- 2106755 TI - [Pathophysiology of the renin-angiotensin system]. AB - The renin angiotensin system is an important system for the regulation of blood pressure and salt and water homeostasis. As a pathogenetic factor it is involved in the development of several forms of renal hypertension and, furthermore, it participates in the pathogenesis of primary and secondary hypertension. The regulation of the activity of the system is under the control of neuronal and hormonal mechanisms and depends on blood pressure and plasma concentrations of sodium chloride. With the development of converting enzyme inhibitors and their vasodilator, diuretic and sympatholytic actions a new important antihypertensive principle for lowering blood pressure was found. In this context also local renin angiotensin systems which have been described for several tissues have to be discussed as a possible target of action for converting enzyme inhibitors. PMID- 2106756 TI - Stability of drugs with enteral nutrient formulas. AB - Experiments were performed to determine the chemical stability and compatibility of cephalexin, cimetidine, diazepam, or propranolol with full-strength and half strength Isocal, Sustacal, and Sustacal HC (Mead Johnson). The enteral nutrient formulas (ENFs) containing the solid or liquid dosage forms were stored at 24 degrees C and samples were taken at times 0, 1.5, 3, 6, 8, 10, and 24 hours. At each sampling time, the mixtures were visually examined for signs of incompatibilities such as precipitation, viscosity changes, and phase separation. Samples from each time period were analyzed by a stability-indicating high performance liquid chromatography (HPLC) method. The drugs mixed with half strength ENFs were also passed through ultrafiltration membranes to separate complexed from uncomplexed drug. Neither visual changes nor variations in pH were observed in any formula. With the exception of cephalexin suspension in half strength ENFs, none of the drug concentrations changed appreciably throughout the study period. The assays performed for undecomposed drug at each sampling time for the various full- or half-strength ENF-solid drug mixtures stored at 24 degrees C for 24 hours ranged from 92.3 to 103.4 percent for cephalexin, 96.2 to 103.0 percent for cimetidine, 93.9 to 106.2 percent for diazepam, and 95.5 to 102.2 percent for propranolol. For the liquid drugs, the concentration ranged from 86.5 to 102.0 percent for cephalexin, 97.0 to 101.1 percent for cimetidine, 98.2 to 103.0 percent for diazepam, and 97.4 to 104.8 percent for propranolol. Ultrafiltration studies showed varying percent binding dependent on the drug studied. PMID- 2106757 TI - Parenteral iron dextran therapy. AB - Parenteral iron therapy is indicated in patients with iron-deficiency anemia associated with conditions that interfere with the ingestion or absorption of oral iron. Replacement doses of iron required to replenish iron stores are based on body weight and the observed hemoglobin value. Methods of administering iron dextran are reviewed, including intramuscular and intravenous injections of the undiluted drug, intravenous infusion of a diluted preparation, and as an addition to parenteral nutrition solutions. The overall incidence of adverse reactions associated with the parenteral administration of iron is low, but the potential for an anaphylactic reaction requires that an initial test dose be given followed by careful patient observation. PMID- 2106758 TI - [Polychlorinated biphenyls (PCB) in fish from hatcheries and clarifying ponds]. AB - The concentrations of six selected single polychlorinated biphenyl (PCB) congeners, for which legal tolerance levels became valid in 1988, and the congener no. 49 (2,2',4,5'-tetrachlorobiphenyl) were determined in the muscle tissue of 58 fishes from fish hatcheries and in 17 fishes from settle ponds. The fish were taken from flowing waters in the years 1986 and 1987. High and low chlorinated biphenyls were present in each sample, but the concentration of the low chlorinated biphenyls was distinctly lower than that of the higher chlorinated ones. Nevertheless these results demonstrate the intake of components of low chlorinated technical PCB mixtures in the environment and food chains. Compared with the investigations carried out in 1980/81 in fishes from fish hatcheries, a decrease of PCB contamination in the muscle tissues with regard to the technical mixture Clophen A 60 was observed. This is in accordance with the results our team obtained a short time previously in muscle tissue from foxes and in food-stuffs. The concentration of all PCB congeners determined in the muscle tissue from fish of settle ponds was significantly higher than in the tissue from fish taken from hatcheries. Thus, the PCB content depends on the PCB load in different environments. Therefore, fishes can be useful as bioindicators for the intake of low and high chlorinated PCB congeners in aquatic ecosystems. PMID- 2106759 TI - [Polychlorinated biphenyls (PCB) in human adipose tissue]. AB - This study describes the contamination of human adipose tissue with six selected polychlorinated biphenyls (PCB) known as "indicator congeners", with PCB no. 49 and the mixed inducer PCB nos. 156, 170, and 189. The low chlorinated biphenyls nos. 28, 49, and 52 could not be found in the tissue samples, while the average concentration of PCB no. 101 was 9.0 micrograms/kg. The content of PCB nos. 138, 153, and 180 was slightly below the values published by the "Deutsche Forschungsgemeinschaft" (DFG). The mixed inducer nos. 138, 156, 170, and 180 amounted to approximately 40% of all the PCBs measured. The PCB contamination was positively correlated with age: for the age group 61-70 years, with the exception of PCB no. 101, a distinct increase in the concentrations could be observed. PMID- 2106760 TI - Antibodies against Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion during early phase of acute otitis media. AB - Serum type (IgG, IgM and IgA-class) and secretory type antibodies specific to Streptococcus pneumoniae (Pn), Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) were measured by enzyme-linked immunosorbent assay (ELISA) in 46 serum and 114 middle ear effusion (MEE) samples from 85 children with acute otitis media (AOM). The samples were obtained within 12 h from the onset of the ear symptoms. Serum (but not secretory) type antibodies to the infecting Pn serotype were found in 24% of the MEE samples of the patients with Pn AOM and, correspondingly, serum and/or secretory type antibodies to Hi and Br were seen in 54% and 63% of the MEE samples of the patients with Hi or Br AOM, respectively. Moreover, antibodies against bacteria other than the causative one could also be found in the MEE. The occurrence of the serum type antibodies against these bacteria in the MEE was closely correlated with their serum levels. The findings of this study indicate that during the very early phase of AOM, the MEE contains both serum type antibodies originating from the serum, and secretory antibodies of middle ear origin. Among them there are antibodies specific to the three most common bacteria causing AOM (Pn, Hi, and Br) regardless of the bacterial etiology of the AOM attack in question. PMID- 2106761 TI - Prevention of experimental acute otitis media with penicillin V. AB - The preventive effect of penicillin V (pcV) in pneumococcal otitis media in the rat has been studied. The pcV was administered either before bacterial challenge (prevention group) or after challenge but before the establishing of acute purulent otitis media (AOM) (early treatment group). In both cases a fulminant infection was avoided. Thus, in the prevention group no animal developed AOM and in the early treatment group the fulminant AOM was avoided in all cases. These results give further support to the idea of using long-term treatment with an antibiotic with a narrow spectrum to avoid recurrent AOM (rAOM). Furthermore the observation that early treatment might stop the development of fulminant AOM indicates another more restrictive possibility to use antibiotic as a prophylactic measure in otitis-prone children. PMID- 2106762 TI - Occurrence of middle ear pathogens in the nasopharynx of young individuals. A quantitative study in four age groups. AB - Colonization of middle ear pathogens (S. pneumoniae, H. influenzae and B. catarrhalis), potential pathogens (S. aureus and coagulase-negative staphylococci) and non-pathogens was determined quantitatively on the posterior wall of the nasopharynx (NPH) of children (four age groups: under 2 years, 2-5 years, 6-10 years and 11-15 years). None of the 90 individuals examined was suffering at the time of bacterial sampling from acute otitis media (AOM), sinusitis, or tonsillitis. All individuals under 2 years of age harboured middle ear pathogens in the NPH, but only 40% of the individuals of the oldest age group (p less than 0.001). Furthermore, in the youngest group, 57% of the cases had pathogens in the NPH, which completely dominated the bacterial flora, i.e. constituted more than 90% of the total bacterial count when calculated as CFU/cm2. The corresponding count in the oldest age group was only 20% (p less than 0.01). One important reason for the high incidence of AOM among young children in particular seems to be the noticeable accumulation of middle ear pathogens in huge quantities in the NPH in this age group. PMID- 2106764 TI - The cost and benefits of coronary heart disease risk factor reduction. Proceedings of a symposium. Siena, Italy, June 10-11, 1989. PMID- 2106763 TI - Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy. AB - The bisphosphonates 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP), 3 amino-1,1-hydroxypropane-1,1-diphosphonic acid (APD), and 1-hydroxyethane-1,1 diphosphonic acid (EHDP) were compared for their ability to inhibit the osteoclastic resorption of bone in culture. This was achieved by measuring the effect of bisphosphonate concentration on the number of resorption pits formed and the total area of resorption. During this analysis, a new application of reflected polarized light microscopy was developed that has advantages over other microscopy techniques, including scanning electron microscopy (SEM), as applied to the analysis of resorbed bone surfaces. Based on area analysis, the bisphosphonates were effective for the range 10(-7)-10(-8) M, with ABP about two to five times more effective than EHDP or APD. Similar data were obtained by counting the number of resorption pits but with EC50 10 times higher. At lower concentrations (10(-9) M), bisphosphonates may enhance the formation of resorption pits. APD was found to be more toxic (10 times) than ABP or EHDP to osteoclasts and mononuclear cells, but toxic concentrations were at least 10(2) times higher than the resorption EC50. These data plus immunofluorescence, SEM, and transient incubation experiments show that it is the bisphosphonate-bone complex that directly inhibits the excavation of resorption pits by mature osteoclasts. The mechanism of action does not appear to require inhibition of osteoclast differentiation or toxic elimination of osteoclasts. Bisphosphonates, however, subtly affect the cytoskeleton of osteoclasts. PMID- 2106765 TI - Costs and benefits of risk factor reduction for coronary heart disease: insights from screening and treatment of serum cholesterol. AB - The principles of cost-effectiveness analysis are straightforward and can be applied to set priorities among competing uses for resources. This article examines the relationship between serum cholesterol and coronary heart disease (CHD) risk, drawing on information from a number of large intervention trials. The cost-effectiveness of treatment alternatives for elevated serum cholesterol, hypertension, and symptomatic CHD are compared. Concern is expressed that the guidelines issued by the National Cholesterol Education Program extend beyond the available evidence and do not adequately take into account problems with adherence to diet and drug regimens or the cost of widespread implementation. The cost-effectiveness of drug treatment for both high cholesterol and hypertension depends on the populations at which they are targeted. PMID- 2106766 TI - The economics of hypertension and stroke. AB - The prevention of stroke through the control of hypertension is cost-effective economically and medically. A reduced incidence of stroke generates savings to the health service in hospital and surgical costs, and the avoidance of premature mortality means survivors contribute more to the economy as a result of extra working years. In addition to financial benefits, antihypertensive agents can also improve a patient's quality of life. This can be measured with a variety of health profiles or indexes and is often expressed together with life expectancy in quality-adjusted life years. This article examines the benefits produced by the effective control of hypertension, taking data from England and Wales during the past 30 years. PMID- 2106767 TI - Outcome assessment in cardiovascular cost-benefit studies. AB - The scarcity of health resources and development of new treatments have introduced a need to assess health care interventions in the areas of both costs and benefits. Information on costs and benefits of one treatment program relative to another can assist decisions about resource allocation by indicating which interventions offer the greatest benefit at the least cost. Economic evaluation is dependent on accurate definition and appropriate measurement of outcome or benefit. This article reviews a number of evaluation techniques and cost-benefit studies associated with cardiovascular medicine. The focus is on health-related quality of life, the methodology, and the problems encountered therein. Methods for combining quantity and quality of life are discussed with reference to a composite measure of health outcome, quality-adjusted life years. PMID- 2106768 TI - Medical management and managing medical care: the dilemma of evaluating new technology. AB - A unique computer simulation model has been developed to investigate the broad clinical and economic effects of changing risk factors for cerebrovascular and cardiovascular disease. The model can be used in countries where good input data are available to provide valuable information to aid policy decisions on medical care. This article describes the computer model, the sources of population and cost data, and the assumptions that must be made when a model of this type is used. The Swedish and U.S. populations are compared, and the results are expressed in years of life saved. Cost-effectiveness of intervention is assessed by combining economic and clinical data, and the most favorable cost effectiveness ratios are found in the elderly population with high levels of serum cholesterol and diastolic blood pressure. In contrast, the costs per year of life saved in the younger population at low risk are comparatively high. PMID- 2106769 TI - The design of future cost-benefit studies. AB - An economic evaluation is designed to prioritize expenditure, aid decision making, and inform medical audit. A good economic evaluation is explicit and clearly describes the alternative therapies to be evaluated. The evaluation takes into consideration the cost of each component and measures outcome in economic benefit and physical, social, and psychologic well-being. A variety of approaches can be used to assess quality of life, and a good economic evaluation will use a range of measures. Costs and outcomes of health care interventions typically accrue across time periods, and the analysis must allow for this. Similarly, data must answer the question; how much does it cost to identify one additional unit of benefit? Because all evaluations are imprecise both in cost and outcome, sensitivity analysis is needed to determine the effect that different assumptions have on the results. PMID- 2106770 TI - Measuring costs and financial benefits in randomized controlled trials. AB - Economic assessment can be incorporated into clinical trials to evaluate and compare the costs and benefits of different health care programs. In this article the three main types of evaluation are discussed: cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis. The measurement of direct and indirect costs is described and specific examples are quoted. Full economic analyses are given for the use of naftidrofuryl in the treatment of acute cerebral hemisphere infarction and the use of auranofin in the treatment of rheumatoid arthritis. Economic evaluation is seen to be justified whenever a more expensive treatment is expected to produce greater benefit. Such analyses should consider quality of life and health status, as well as the more easily identifiable outcomes. PMID- 2106771 TI - Regulatory demands for cost-benefit studies. AB - In 1987 to 1988 there was a significant increase in drug costs in Australia. This was largely the result of the introduction of angiotensin-converting enzyme inhibitors into clinical practice. In this article the implications of escalating drug costs are examined. The impact of revolutionary new drugs is considered, and it is questioned whether even a relatively wealthy country, such as Australia, can afford the high costs of these new agents. The Australian Pharmaceutical Benefits Scheme is discussed, and modification of this into a two-tier system is proposed. A two-tier system could preserve the present list and the essential elements of the current scheme but would introduce a second list of new drugs for which a premium would be charged. Such a system could recoup costs generated by new drugs and also restrict overprescribing but may limit the prescription of new drugs to less well-off persons. The article concludes by considering the total health care budget, taking into account the relative cost-benefit expenditures of hospital care and drug therapy. PMID- 2106772 TI - Overview: economic evaluation and coronary heart disease. PMID- 2106773 TI - Effect of elective hospitalization on plasma lipoprotein cholesterol and apolipoproteins A-I, B and Lp(a). PMID- 2106774 TI - Increased muscle dynamic endurance associated with weight reduction on a very-low calorie diet. AB - To assess muscle function after a period of negative energy balance, 32 obese women were placed on a 544-kcal/d, high-protein diet for 4 wk. Weight loss was associated with a decrease in the waist-to-hip-circumference ratio (WHR) and significantly higher emptying of abdominal than gluteal fat cells. The low calorie regimen was associated with a significant increase in isokinetic muscle endurance, a decrease in glycogen concentration, and an increase in glycogen synthase (GS) activity and its fractional velocity (FV). The GS activity and its FV were negatively correlated with the WHR before treatment whereas their subsequent increase was correlated with the decrease in WHR. Dietary treatment produced a decrease in the isokinetic muscle strength, which was correlated with the reduction in lean body mass. The improvement in dynamic endurance observed after energy restriction parallels not only the increase in GS activity in muscle but also the decrease in glycogen stores and glucose oxidation, and most probably depends on the increased utilization of fatty acids. PMID- 2106775 TI - Reduced arachidonate in serum phospholipids and cholesteryl esters associated with vegetarian diets in humans. AB - Lipid fractions such as phospholipids (PLs), cholesteryl esters (CEs), and free fatty acids (FFAs) represent source pools for eicosanoid synthesis. To determine whether dietary habits affect the enrichment of 20:4n-6 in these precursor pools, we studied humans with partial or complete arachidonate restriction resulting from chronic avoidance of animal fat and tissue. Fasting serum was obtained from omnivorous control subjects (Omni, n = 100), semivegetarians (Semiveg, n = 16), and vegetarians (Veg, n = 25). PLs, CEs, FFAs, and triglyceride (TG) fatty acids were quantitated by thin-layer and gas chromatography. Serum 20:4n-6 was lower in the PL fraction in both Veg (p less than 0.01) and Semiveg groups (p less than 0.05) than in the Omni group and lower in the CE fraction in the Veg group (p less than 0.05). Serum 18:2n-6 did not differ between groups for any serum lipid fraction. 18:3n-3 was elevated in PLs and CEs of both Veg (p less than 0.05 and 0.01) and Semiveg groups (p less than 0.05 and 0.01) compared with the Omni group but did not result in differences in 20:5n-3 in PLs or CEs between diet groups. The lower concentration of 20:4n-6 in serum PLs and CEs of the Veg group indicates that dietary arachidonic acid enriches its circulating pool in humans; however, 20:5n-3 is not similarly responsive to dietary restriction. PMID- 2106776 TI - Long-term parenteral nutrition in unrestrained nonhuman primates: an experimental model. AB - A freely mobile jacket and tether system was developed for the investigation of total parenteral nutrition (TPN)-induced metabolic bone disease and complications of prolonged TPN in 12 Macaca fascicularis nonhuman primates. The animals received TPN for 49 +/- 7 d (means +/- SEM), providing 82 +/- 2 kcal.kg-1.d-1. Serum glucose increased from 3.6 +/- 0.2 mmol/L at baseline to 8.3 +/- 1.9 mmol/L (p less than 0.01) during TPN, and serum albumin decreased from 38 +/- 1 g/L at baseline to 29 +/- 1 g/L (p less than 0.001) during 2.75% amino acid TPN and 30 +/- 2 g/L (p less than 0.01) during 5% amino acid TPN infusion. No significant changes were seen in serum prealbumin, total protein, bilirubin, alanine aminotransferase, and 5'-nucleotidase during TPN infusion. Major complications included catheter sepsis, hyperglycemia, diarrhea, and premature death in six animals. Thus, metabolic complications of prolonged TPN support may be investigated in a freely mobile nonhuman primate. PMID- 2106778 TI - Rapid immunoperoxidase demonstration of Rickettsia rickettsii in fixed cutaneous specimens from patients with Rocky Mountain spotted fever. AB - Immunofluorescence (IF) of skin biopsies for detection of Rickettsia rickettsii (RR) has proven useful as a rapid test for confirmation of Rocky Mountain spotted fever (RMSF). However, IF lacks sensitivity, requires special equipment and training, and is difficult to interpret. The authors have developed an indirect avidin-biotin immunoperoxidase (IP) technique to detect RR in fixed and frozen tissue sections. The technique was evaluated on fixed cutaneous specimens from patients dying of RMSF and compared to specimens from control patients dying of an acute febrile illness with skin manifestations and vasculitis. IP correctly identified RR in 9 of 12 cases with probable identification in 2 additional cases. Of 11 controls, 10 were negative and one was uninterpretable. RR was easily visualized within cytoplasm and nuclei of endothelial cells in association with perivascular lymphocytic infiltrates and less frequently with vasculitis or non-inflamed vasculature. IP is rapid, amplifies small quantities of antigen, gives excellent histologic detail as compared with IF, and is easily adapted for use in hospitals with immunoperoxidase capabilities. PMID- 2106777 TI - Abnormality of von Willebrand factor in patients with hemoglobin E-beta (0) thalassemia. AB - The authors have identified six Southeast Asian patients ranging in age from 14 to 21 years with hemoglobin E-beta(0) thalassemia and a coagulopathy involving von Willebrand factor (vWF). These patients had normal or only slightly decreased plasma clotting factor levels. The activated partial thromboplastin time was prolonged in four of the patients. The abnormal feature common to all patients was a qualitative loss of high molecular weight multimers of vWF by crossed immunoelectrophoresis (vWF:CIE). Plasma vWF antigen concentration (vWF:Ag) and ristocetin cofactor activity (vWF:RCo) also were decreased and bleeding time prolonged in three patients. Epistaxis was present in two. No family history of increased bleeding tendency was present in any patient. Coagulation parameters and vWF:CIE were normal in two first-degree relatives without this hemoglobinopathy. vWF abnormalities and clinical manifestations were greatest in those patients with the most severe anemia and hepatosplenomegaly. These six patients appear to have an acquired abnormality of vWF, although they lack the clinical characteristics of acquired von Willebrand disease. While the etiology of this abnormality is unclear, the authors speculate that proteolysis of vWF secondary to extramedullary hematopoiesis or loss through high cardiac output shear stress in these anemic patients may be involved. PMID- 2106779 TI - Use of Gen-Probe and Bactec for rapid isolation and identification of mycobacteria. Correlation of probe results with growth index. AB - Gen-Probe culture confirmation tests (Gen-Probe, San Diego, CA) for Mycobacterium tuberculosis complex and Mycobacterium avium complex were performed on 276 mycobacterial isolates. All 138 M. tuberculosis complex isolates and 79 of 80 M. avium complex isolates were identified correctly. No falsely positive test results were obtained; 58 nontuberculous mycobacteria other than M. avium complex were negative by Gen-Probe. In a second phase of testing, Gen-Probe tests were performed using concentrates from 101 patient Bactec 12B cultures. Positive results by Gen-Probe tests were correlated with the growth index (GI) reading on the day of processing as well as the accumulated GI readings. For those 51 with high (greater than or equal to 999) final GIs, 40/40 (100%) M. tuberculosis complex isolates and 9/11 M. avium complex isolates were positive by Gen-Probe, and six other mycobacteria were negative. Of the 25 with moderate final readings (400 less than or equal to GI less than 999), 12/17 M. tuberculosis complex isolates and 1/1 M. avium complex isolates were correctly identified by Gen Probe; seven other mycobacteria were negative. Of 25 with low readings (GI less than 400), 8/24 M. tuberculosis isolates were correctly identified by Gen-Probe, and no falsely positive test results were obtained with the other probes. All true negative tests on seven other mycobacteria (not M. tuberculosis complex or M. avium complex) had less than 2% hybridization. Of the 24 falsely negative tests on M. tuberculosis complex isolates or M. avium complex isolates, 22 had greater than 2% hybridization with their respective probes. Thus, percent hybridization greater than 2% may be a useful indicator of the need for retesting. PMID- 2106780 TI - Cloxacillin-induced cholestasis in a renal allograft patient with chronic hepatitis. PMID- 2106781 TI - Hospital charges and reimbursement for alteplase and streptokinase. PMID- 2106782 TI - Formulary-control procedures in a staff-model health maintenance organization. AB - Efforts to promote cost-effective drug prescribing in a health maintenance organization (HMO) through (1) revision of the formulary, (2) education, and (3) drug-use evaluations (DUEs) are described. New programs and procedures to promote more cost-effective prescribing were implemented in 1987 at a staff-model HMO with seven health-care centers and 40,000 members. Support to the pharmacy and therapeutics committee in developing formulary recommendations was enhanced, the formulary was revised and the number of listed drugs reduced by half, the focus of pharmacists was changed from purchasing and inventory control to education of physicians about cost-effective prescribing, and the most expensive drug categories were identified and educational efforts instituted. During the next two years substantial changes in the prescribing of oral contraceptives, nonsteroidal anti-inflammatory drugs, antiulcer agents, and anti-infectives, but not antihypertensive drugs, were identified through DUEs. Evaluation of cost savings was limited by the lack of an automated, integrated patient database, and it was difficult to assess the effect of changes in patient population. Revision of the formulary coordinated with enhanced educational efforts and DUEs resulted in more cost-effective prescribing in an HMO without placing severe restrictions on physicians or patients. PMID- 2106783 TI - Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis. AB - PURPOSE: To compare the efficacy and safety of recombinant human tissue-type plasminogen activator (rt-PA, supplied as Activase) with heparin alone or rt-PA plus heparin in the treatment of venographically documented proximal deep venous thrombosis (DVT) of the leg. PATIENTS AND METHODS: Sixty-four patients underwent 65 randomizations to rt-PA alone (n = 36), rt-PA plus heparin (n = 17), or heparin alone (n = 12) in a prospective, multicenter, randomized, open-label trial, with efficacy assessed by a radiology panel unaware of treatment assignment. Patients randomly assigned to rt-PA received 0.05 mg/kg/hour for 24 hours via a peripheral vein, with a maximum dose of 150 mg. All patients then received heparin and warfarin for the remainder of the hospitalization. Follow-up venography was performed 24 to 36 hours after initiation of therapy. RESULTS: Complete or more than 50% lysis occurred in 10 (28%) patients treated with rt-PA, five (29%) patients with rt-PA plus heparin, and no patient treated with heparin. No lysis occurred in 16 (44%) patients treated with rt-PA plus heparin, and 10 (83%) patients who received heparin alone (p = 0.04). There was one major complication, a nonfatal intracranial hemorrhage in a patient who received rt-PA alone. At 7 to 10 days after initiation of treatment, the level of serum glutamic oxaloacetic transaminase nearly doubled among all patients, including those assigned to receive heparin alone. CONCLUSION: (1) rt-PA and rt-PA plus heparin cause more clot lysis than heparin alone; (2) the addition of heparin to rt-PA does not improve the lysis rate; (3) DVT treated with heparin is commonly associated with a rise in the transaminase level; (4) heparin does not increase the risk of bleeding from rt-PA therapy; and (5) alternative dosing regimens and modes of administration of rt-PA should be investigated to improve further its efficacy and safety in the treatment of acute DVT. PMID- 2106784 TI - Meningococcemia: an undescribed cause of community-acquired bacteremia in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. PMID- 2106785 TI - Concurrent existence of heterotopic ossification and thrombophlebitis. PMID- 2106786 TI - A ring X chromosome, 46,Y,r(X)(p22.33q28), as a cause of extreme short stature in a male. AB - We describe a 15 10/12-year-old boy (Tanner stage 4, peak growth velocity 7 cm/year) with a ring X chromosome who presented with extreme short stature (mean 5.3 SD) as the sole recognizable abnormality. His chromosome constitution was determined to be 46,Y,r(X)(p22.33q28) in 174 of 182 peripheral blood cells and in 35 skin fibroblasts. Of the remaining eight peripheral blood cells, five had a dicentric double-size ring and three had a smaller ring. Other laboratory studies for short stature were noncontributory. We suspect that the ring's specific behavior in mitosis or its effect on expression of the statural determinant on the X chromosome short arm may be responsible for short stature in this patient. PMID- 2106787 TI - The effect of aging on hypothalamic function in oophorectomized women. AB - To detect age-related changes intrinsic to hypothalamic-pituitary function, we studied plasma gonadotropin levels in 12 oophorectomized women ages 27 to 64 years who were not undergoing hormone replacement therapy. Blood drawn from an indwelling catheter every 10 minutes for 5 hours was assayed for follicle stimulating hormone, luteinizing hormone, estradiol, and prolactin concentrations. All estradiol levels were less than 20 pg/ml and prolactin values were normal. Mean gonadotropin concentrations, pulse frequency, and pulse amplitude were no different in women aged 27 to 49 years as compared with subjects 52 to 64 years old. When grouped according to gynecologic age (years since puberty) or years after oophorectomy, luteinizing hormone and follicle stimulating hormone mean concentrations, mean pulse frequency, and mean pulse amplitude were comparable to those grouped according to chronologic age. On the basis of our findings, lack of response from postmenopausal ovaries to endogenous gonadotropin stimulation is a result of primary age-related change in the ovary, not in the hypothalamus. PMID- 2106788 TI - Induction of class II major histocompatibility complex antigen expression in human granulosa cells by interferon gamma: a potential mechanism contributing to autoimmune ovarian failure. AB - We investigated the possibility that major histocompatibility complex (MHC) class II antigens and interferon gamma, a product of activated T lymphocytes, play a role in human autoimmune oophoritis. MHC class II molecules initiate immune responses by presenting antigens to T-helper lymphocytes; interferon gamma can induce class II antigen expression at ectopic sites and has been implicated in the cause of various autoimmune disorders. We studied the expression of class II MHC antigens in ovaries from normal women of reproductive-age and from women with premature autoimmune ovarian failure. Immunoperoxidase technique applied to tissue sections of nine normal human ovaries revealed class II MHC antigen expression only on occasional cells of macrophage morphology; granulosa cells were negative regardless of stage of follicular maturation. In contrast, extensive and intense class II antigen expression was observed in granulosa cells in ovarian biopsy sections from four patients with premature autoimmune ovarian failure. Immunofluorescence and radioimmunoassay techniques used to detect and quantitate MHC antigens revealed that class II antigen expression could be induced and class I MHC antigen expression was enhanced in granulosa cell cultures after the addition of interferon gamma. These data provide evidence that autoimmune oophoritis is associated with ectopic expression of MHC class II antigens by ovarian granulosa cells, and that this phenomenon can be induced by the immunologic cytokine interferon gamma. PMID- 2106789 TI - Severe ocular anterior segment ischemia after long-term trifluridine treatment for presumed herpetic keratitis. PMID- 2106790 TI - Elimination of the risk of needle-stick injury in handling donor eyes. PMID- 2106791 TI - Evaluating productivity and profitability in occupational therapy contractual work. AB - The availability of contractual work for occupational therapists is increasing steadily. Because of time constraints, therapists often must select one contract over another. To help the therapist make informed decisions, this paper provides a step-by-step process for developing a trend analysis to compare the productivity and profitability of contracts. A case example taken from the author's own experience illustrates this process. PMID- 2106792 TI - Origin of dopamine in the rat adrenal cortex. AB - The hypothesis that dopamine (DA) is involved in the control of aldosterone secretion is given some support by the finding of DA in the adrenal cortex of several species, but the source of this DA is not known. This study showed that the administration of L-dopa to intact rats or medullectomized rats caused a significant DA increase in the adrenal cortex. The DA increase in the cortex was more pronounced than in the medulla, coincident with higher L-dopa uptake by the cortical tissue. Tyrosine administration raised DA levels only in the medulla. Sympathectomy of the rat by 6-hydroxydopamine treatment did not affect DA basal levels in the cortex or the DA increase in this tissue after L-dopa injection. 3,4-Dihydroxyphenylacetic acid (DOPAC) is detectable in the adrenal cortex but not in the adrenal medulla, and DOPAC levels increased significantly after L dopa, which indicates monoamine oxidase (MAO) activity within the adrenal cortex. Because 6-hydroxydopamine pretreatment did not alter DOPAC levels, cortical MAO may be located outside catecholaminergic neurons. The results established circulating L-dopa as a precursor for DA in the adrenal cortex of the rat. They also showed that tyrosine hydroxylase activity is absent from the adrenal cortex of this species. PMID- 2106793 TI - Ouabain-induced lethal proximal tubule cell injury is prevented by glycine. AB - Exposure to 1 mM ouabain for greater than 30 min caused lethal cell injury to isolated rabbit proximal tubules as measured by increased lactate dehydrogenase release. Addition of 2 mM glycine or glutathione to the incubation medium prevented this injury and a sharp fall of cell ATP that accompanied it. Glycine and glutathione did not alter rapid, early effects of ouabain to deplete cell K+ and inhibit respiration. Preservation of cellular glutathione was not required for protection. Glycine did not ameliorate ouabain-induced increases of cell water and did not prevent lethal cell injury associated with cell swelling produced by incubation in a high K+ concentration medium. In contrast, 100 mM mannitol, which at least partially ameliorated swelling in both ouabain and high K+ medium, prevented lethal injury in high-K+ medium and decreased it in the presence of ouabain. The combination of glycine and mannitol completely prevented ouabain-induced lethal injury and cell water increases. These observations indicate that glycine, unlike mannitol, does not protect against primary volume induced insults. Ouabain-induced lethal cell injury results from a process that includes both a volume component ameliorated by mannitol and a volume-independent component that is prevented by glycine and is closely associated with accelerated ATP depletion. PMID- 2106794 TI - NaCl modulates captopril effects on glomerular prostaglandin synthesis and glomerular filtration. AB - Captopril stimulates glomerular prostaglandin (PG) synthesis and increases glomerular filtration rate (GFR) in Na-repleted rats, whereas, in Na-depleted rats, it fails to stimulate PG synthesis and decreases GFR. In the present work the influence of chronic and acute NaCl loading on PG synthesis and renal function was studied in Na-depleted rats receiving captopril (LNC rats). Glomerular PGE2 and 6-keto-PGF1 alpha were not increased in LNC rats and were significantly lower than in Na-depleted rats (LN). Na repletion, while continuing captopril, increased PG synthesis above control levels. Addition of captopril in vitro to the incubation medium stimulated PGE2 synthesis in glomeruli of control rats, whereas it depressed it in LN rats. Acute loading with NaCl in LNC rats increased inulin and PAH clearances to values significantly greater than in control rats and similar to those of normal rats receiving captopril. Comparable volume loading with isotonic mannitol or 3% albumin increased inulin and PAH clearances only to control values. The specific effect of NaCl in acute loading was prevented by cyclooxygenase inhibition and was not mediated by increased systemic blood pressure. The results provide evidence that the effects of captopril on glomerular PG synthesis and renal function depend on the state of Na balance. PMID- 2106795 TI - Quantitation of total carbon dioxide in nanoliter samples by flow-through fluorometry. AB - A new ultramicrofluorometric assay for the measurement of picomole amounts of total CO2 is described. The assay is based on a sequence of two linked enzymatic reactions: HCO3 reacts with phosphoenolpyruvate forming oxaloacetate, and oxaloacetate is then converted to malate with associated oxidation of NADH to NAD+. The fluorescence of NADH is measured in a modified ultramicrofluorometer. The HCO3 content of the sample is proportional to the decrease in NADH fluorescence. The method can resolve differences as small as 5.5 pmol total CO2 in 3-nl samples containing 0-160 pmol. The assay is 5- to 10-fold more sensitive than the widely used microcalorimetric assay. The assay can also measure total CO2 in biological samples. The assay will be useful in measuring transepithelial total CO2 transport in short distal nephron segments with low rates of total CO2 transport without resorting to extremely long collection times. PMID- 2106796 TI - Mechanism underlying responses to histamine of isolated monkey and human cerebral arteries. AB - Cerebral artery strips obtained from Japanese monkeys partially contracted with prostaglandin F2 alpha responded to histamine with a relaxation that was attenuated by treatment with cimetidine or chlorpheniramine and was abolished by their combined treatment. Endothelium denudation suppressed the relaxation; the remaining relaxation was not influenced by the H1 antagonism but was abolished by the H2 antagonism. Treatment with methylene blue slowed the development of relaxation and, in the presence of cimetidine, depressed the magnitude of relaxation. Indomethacin did not alter the response. In the main trunk of human middle cerebral arteries obtained during autopsy, histamine predominantly caused contractions, whereas third and fifth branches responded exclusively with a dose dependent relaxation. The contraction was abolished by chlorpheniramine, and the relaxation was attenuated by either chlorpheniramine or cimetidine. Removal of endothelium suppressed or reversed the relaxation to a contraction. It appears that the histamine-induced relaxation is mediated by endothelial H1 receptors responsible for the release of endothelium-derived relaxing factor and also by H2 receptors in smooth muscle, whereas the contraction is associated with activation of smooth muscle H1 receptors. Involvement of the receptor subtypes in the observed response of monkey and human cerebral arteries quantitatively differs. Physiological and pathophysiological roles of endogenous histamine acting on the large cerebral arteries may be postulated. PMID- 2106797 TI - Impaired endothelium-dependent relaxations in hypertensive resistance arteries involve cyclooxygenase pathway. AB - Endothelial cells modulate vascular tone by releasing endothelium-derived relaxing (EDRF) and contracting factors. An imbalance of these factors in hypertension could contribute to increased peripheral vascular resistance. Mesenteric resistance arteries of Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were suspended in a myograph filled with physiological salt solution (37 degrees C; 95% O2-5% CO2). In WKY rings contracted with norepinephrine, acetylcholine (10(-9)-10(-4) M) evoked endothelium-dependent relaxations (88 +/- 2%, IC50 7.3 +/- 0.1; n = 31). Hemoglobin (10(-5) M) but not meclofenamate (10(-5) M) reversed the relaxations delineating EDRF as the mediator. Nitric oxide (3 X 10(-9)-10(-5) M) induced comparable relaxations as acetylcholine. In SHRSP, relaxations to acetylcholine but not those to nitric oxide were impaired (61 +/- 5%, IC50 greater than 6.6 +/- 0.4; n = 24; P less than 0.005). In SHRSP, meclofenamate but not the thromboxane synthetase inhibitor CGS 13080 normalized endothelium-dependent relaxations. Relaxations to sodium nitroprusside were enhanced in SHRSP both in rings with and without endothelium. Thus our results are compatible with the concept that endothelium-dependent relaxations in resistance arteries are mediated by nitric oxide. In SHRSP, endothelium-dependent relaxations are impaired because of a cyclooxygenase-dependent substance interfering with the release and/or action of EDRF. PMID- 2106798 TI - Influence of vessel size on the sensitivity of porcine coronary microvessels to nitroglycerin. AB - The responses of small (60-100 microns), medium (101-190 microns), and large (191 300 microns) porcine coronary microvessels to nitroglycerin were examined in vitro using a video-imaging apparatus. Large coronary microvessels, preconstricted with acetylcholine, relaxed by 90% in response to nitroglycerin, whereas small microvessels relaxed only 20% to nitroglycerin. Responses to putative metabolites of nitroglycerin, S-nitrosocysteine, and nitric oxide, were also examined. S-Nitrosocysteine produced equal relaxations in all sizes of coronary microvessels. Nitric oxide was 10 times more potent in large coronary arteries than in small but produced greater than 90% relaxation of all sizes of coronary microvessels at the highest concentrations. Bradykinin and the calcium ionophore A23187, which release endothelium-derived relaxing factor (EDRF), produced similar relaxation in small, medium, and large microvessels. The compound LY 83583 (which depletes vascular guanylate cyclase) reduced responses to nitroglycerin, nitric oxide, S-nitrosocysteine, bradykinin, and the calcium ionophore A23187 in microvessels of all sizes. Our data are compatible with the concept that nitroglycerin must undergo reductive processing to exert its vasodilator effect, likely through the formation of nitrosothiols. In small coronary microvessels, this biotransformation of nitroglycerin is diminished compared with larger coronary arteries. This may be caused by a relative deficiency of available sulfhydryl groups or a lack of enzymes necessary for conversion of nitroglycerin to its active metabolites in small coronary resistance vessels. PMID- 2106799 TI - Graded modulation of frog microvessel permeability to albumin using ionophore A23187. AB - We investigated the exchange of water and macromolecules across venular microvessels after permeability was increased. Quantitative fluorescence microscopy was used to measure albumin permeability coefficients in individually perfused microvessels of decerebrate frogs. Control permeability coefficient was 2.3 +/- 0.25 X 10(-7) cm/s. Solvent drag increased the apparent solute permeability coefficient (Ps) by 0.57 +/- 0.05 X 10(-7) cm/s for each cmH2O increase in microvessel pressure. The divalent cation ionophore A23187 (0.1-5 microM) produced a transient increase in Ps to a peak value (within 1-3 min), followed (after 4-8 min) by a sustained increase in permeability (16-34% of peak values). Peak values of Ps were 13 and 80 times control for 0.1 and 5 microM A23187, respectively. Both diffusion and solvent drag contributed to the sustained increase in Ps. The equivalent pore radius of the structures determining diffusion and solvent drag was less than or equal to 25 nm during the sustained increase in permeability, smaller than observed gaps between adjacent endothelial cells. The basement membrane and a fibrous matrix secreted by endothelial cells into the gaps may offer resistance to exchange in the high permeability state. PMID- 2106801 TI - Pyridoxine and thyroid function. PMID- 2106800 TI - Microcirculatory responses to exogenous endothelial cell-derived relaxing factor. AB - Endothelium-derived relaxing factor (EDRF) plays an important role in the vasodilatory responses of large blood vessels. However, such a role has yet to be conclusively shown for the microvasculature. In this study we tested the sensitivity of arterioles in the cheek pouch of pentobarbital-anesthetized hamsters to the EDRF-dependent agonists bradykinin and A23187, as well as to exogenous EDRF from cultured bovine aortic endothelial cells. The pouch superfusion fluid was arranged to first pass through a column containing endothelial cells and then on to the tissue. Bradykinin (10-30 nM) or A23187 (0.3 microM) was introduced either upstream or downstream to the endothelial cells, and the resultant responses were measured with video microscopy. Bradykinin and A23187 both caused a dose-dependent release of a microvessel dilator from cultured endothelial cells. We take this dilator to be EDRF based on the characteristics of the responses to the stimuli. Indomethacin (7.7 microM) was present in the superfusate to eliminate the production of cyclooxygenase products from the endothelial cells, and the magnitude of the response was diminished if the superfusate was first passed through a 3-min delay coil before arrival at the pouch. The arterioles dilated to the direct application of bradykinin in a dose dependent fashion. They did not respond however to the direct application of A23187. These studies demonstrate that arteriolar smooth muscle is able to respond to exogenous EDRF and support the premise that EDRF may play an active role in the regulation of blood flow in the microcirculation. PMID- 2106802 TI - Severe hematologic toxicity of valproic acid. A report of four patients. AB - Four patients with severe cerebral palsy, mental retardation, and seizures who were treated with valproic acid showed a broad spectrum of hematologic toxicity, which included thrombocytopenia, macrocytic red cells with or without anemia, and the Pelger-Huet anomaly in the segmented neutrophils, along with elevated vitamin B12 levels, normal serum folic acid levels, and elevated fetal hemoglobin values (two cases). Bone marrow findings in all four patients were abnormal, suggestive of a myelodysplastic syndrome. These hematologic findings have not been previously reported and are important for monitoring a patient on valproic acid therapy. The Pelger-Huet anomaly may be mistaken for an elevated band count, the macrocytic anemia appears not to be secondary to a vitamin B12 or folate deficiency, and the thrombocytopenia may be sensitive to drug dosage. The bone marrow changes appear to be a drug-related myelodysplastic phenomenon. PMID- 2106803 TI - Effects of arachidonic acid on hepatic lipids in ethanol-fed rats. AB - The effects of arachidonic acid supplementation on rats fed ethanol employing an ad libitum schedule have been reported to be different from those observed when rats are fed in more limiting, matched fashion. To reexamine this issue, rats were fed unrestricted amounts of a diet in which 36% of the energy was provided by either ethanol or isocaloric amounts of carbohydrate. In half the animals, 7% of fat consisted of arachidonic acid. Despite earlier reports to the contrary, arachidonic acid had no effect on weight gain and did not attenuate the ethanol induced fatty liver. Arachidonate supplementation tended to increase hepatic total lipids and triacylglycerols, and to potentiate the ethanol-induced elevation of cholesterol esters. Our present results are consistent with those previously reported using pair-feeding techniques in which dietary intakes are somewhat limited. Thus, regardless of the feeding technique employed, relative arachidonic deficiency cannot be involved to explain the lipid accumulation observed after chronic ethanol consumption. PMID- 2106804 TI - [Continuous intragastric pH measurement in intensive care patients treated with ranitidine and tube feeding]. AB - We studied 22 critically ill patients on long-term mechanical ventilation using continuous intragastric pH monitoring with an antimony electrode. Intragastric pH profiles were established for the duration of mechanical ventilation (mean: 7 days). The aim of our study was to achieve a gastric pH between 3.0 and 4.5 utilizing the H2-receptor antagonist ranitidine and nasogastric feeding with Nutricomp F. Patients were divided into three groups which were given (A) ranitidine boluses, (B) continuous ranitidine infusions, or (C) continuous ranitidine infusions together with enteral nutrition via the nasogastric tube. In group B we were able to obtain a pH value between 3.0 and 4.5 only in 11.6% of the observation period. With ranitidine boluses, there were even less measurements (9.3%) in the "optimal" pH range. The combination of continuous ranitidine application together with enteral alimentation made our attempts slightly more successful (20.0%). This failure to achieve the desired pH range encourages airway colonisation and nosocomial pneumonia at gastric pH greater than 4.5. At pH less than 3.0 there is a significantly higher incidence of acute stress ulcerations. Other therapeutic regimens e.g. the application of pirenzepine and sucralfate offer adequate protection of the gastric mucosa without raising the pH level. PMID- 2106805 TI - [The arterial-end tidal CO2 partial pressure difference during anesthesia]. AB - Arterial CO2 partial pressure (PaCO2) can be continuously and noninvasively estimated by monitoring end-tidal CO2 partial pressure (PetCO2). However, the difference between the two (P(a-et)CO2) may vary considerably between patients. In 26 patients undergoing general anesthesia for various surgical procedures, P(a et)CO2 was measured. We tested the hypothesis that certain clinical characteristics are associated with higher P(a-et)CO2 values in a given patient. In addition, we tested the hypothesis that P(a-et)CO2 remains constant during anesthesia by comparing the mean of eight P(a-et)CO2 values, which were measured at 15-min intervals, with the initial (P(a-et)CO2 value. Impaired lung function, defined as a lung score above 6, age above 50 years, and overweight (defined as greater than 120% of ideal body weight) were associated with increased P(a-et)CO2 (mean +/- SD: 6.27 +/- 1.85; 5.27 +/- 2.11; and 6.19 +/- 1.95 mmHg respectively) when compared to normal lung function (lung score less than or equal to 6), age below 50 years, and normal weight (less than 120% of ideal body weight, 3.87 +/- 2.31; 3.55 +/- 2.58; and 3.77 +/- 2.25 respectively). Although these differences are statistically significant, the standard deviations are large and do not allow the prediction of P(a-et)CO2 in a given patient. Initial P(a-et)CO2 correlated well with subsequent P(a-et)CO2 (R = 0.91, P less than 0.001). The mean difference of the subsequent P(a-et)CO2 values from the initial values was 0.05 +/- 0.80 mmHg (mean +/- SD) and was not significantly different from zero. In the patient population studied, P(a-et)CO2 thus remained generally constant during anesthesia. PMID- 2106806 TI - Ibuprofen pretreatment inhibits prostacyclin release during abdominal exploration in aortic surgery. AB - Mesenteric traction during aortic surgery produces facial flushing, reduced mean arterial pressure (MAP), and systemic vascular resistance (SVR) with increased heart rate (HR) and cardiac index (CI). Elevated 6-keto-prostaglandin-F1 alpha (6 keto-PGF1 alpha) suggests prostacyclin is the mediator. To test this hypothesis, the cyclooxygenase inhibitor, ibuprofen (n = 14), or placebo (n = 13) was administered to patients electively scheduled for aortic reconstruction. The hemodynamic measurements and plasma concentrations of prostanoids between groups were compared immediately before (0), and 5, 10, 15, 30, and 45 min following mesenteric traction. Following mesenteric traction significant differences (P less than 0.05) were observed between the ibuprofen pretreatment and placebo group over time in SVR, MAP, HR, CI, 6-keto-PGF1 alpha, and thromboxane B2 (TXB2). Significant differences between groups at individual times were found in SVR, HR, CI, 6-keto-PGF1 alpha, and TXB2. In the placebo group flushing was accompanied by reduced SVR and MAP and increased HR and CI. The greatest effect was seen at 10 min and resolved over 30 min. Plasma concentration of 6-keto-PGF1 alpha increased from 159 +/- 103 (mean +/- SEM) pg/ml to a peak value of 3,765 +/ 803 at 10 min. A late increase in TXB2 occurred with a peak value of 1,970 +/- 891 (mean +/- SEM) pg/ml at 30 min. In the ibuprofen pretreated group no significant changes occurred in hemodynamic measurements or concentrations of prostanoids. The inhibition of 6-keto-PGF1 alpha and its associated hemodynamic changes in the treatment group, but not in the placebo group, confirms the hypothesis that prostacyclin is the mediator of the mesenteric traction response in abdominal aortic surgery. PMID- 2106807 TI - Percutaneous extracorporeal CO2 removal in a patient with bullous emphysema with recurrent bilateral pneumothoraces and respiratory failure. PMID- 2106808 TI - Pathogenesis of AIDS in hemophilia. PMID- 2106809 TI - The adequacy and cost effectiveness of routine resuscitation-area cervical-spine radiographs. AB - Portable resuscitation-area cervical-spine radiographs (PCS) frequently constitute a routine part of the emergency evaluation of patients suffering from blunt trauma. Their adequacy and cost were evaluated by reviewing the records of 92 consecutive trauma patients. Forty-seven of 74 patients (63.5%) had adequate PCS in that all seven cervical vertebrae were visualized. In 27 patients (36.5), all seven cervical vertebrae were not adequately visualized. Inadequate studies were most likely to occur in patients with abnormal vital signs on admission (56%) (P less than .01) and in those subsequently requiring general anesthesia (34.5%). Fifteen patients were intubated without difficulty by maintaining neck immobilization because of uncertainty regarding cervical-spine injuries. The annual cost of inadequate cervical-spine studies was estimated to be $31,000.00. Although the four cervical-spine injuries were diagnosed by the portable technique, routine PCS were frequently inadequate in visualizing all seven cervical vertebrae. Major decisions concerning intubation and surgery frequently had to be made before adequate radiographic evaluation could be completed. It is suggested that time and money are lost by routinely doing a single lateral portable cervical radiograph. It is more appropriate to obtain complete radiographic studies after life-threatening injuries are addressed while patients are treated using the standard techniques of neck immobilization. PMID- 2106810 TI - The diagnostic utility of flumazenil (a benzodiazepine antagonist) in coma of unknown etiology. AB - The use of flumazenil, a benzodiazepine antagonist, was studied in two patients with coma of unknown etiology. One patient ingested 20.5 mg alprazolam before crashing his truck into parked automobiles. The patient was awakened by flumazenil administration, and the severity of his injuries was evaluated reliably. A second patient ingested 7.5 mg triazolam and attempted suicide with carbon monoxide from car exhaust. His coma resolved completely after the administration of the double-blind study drug, obviating treatment with hyperbaric oxygen. Flumazenil had a clear diagnostic and therapeutic role in the treatment of these patients and should be a useful tool for emergency physicians and toxicologists. PMID- 2106811 TI - Surgical intervention in the treatment of pulmonary disease caused by drug resistant Mycobacterium tuberculosis. AB - Of 99 patients with pulmonary disease caused by multiple-drug-resistant strains of Mycobacterium tuberculosis admitted to the National Jewish Center for Immunology and Respiratory Medicine from 1983 to 1988, 29 were selected for resection to supplement chemotherapy. All patients had organisms with high levels of resistance to all of the first line medications, including rifampin and isoniazid. Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 20 of 29 were still sputum-culture-positive at the time of surgery. The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 27 of 29. Pneumonectomy was done in 15 patients; lobectomy or lobectomy plus was done in 14. Although physiologic studies before surgery indicated significant respiratory impairment in many of the patients, there were no operative deaths. There were two unrelated deaths in this series. Of the 27 survivors, 25 have remained sputum-culture-negative for a mean duration of 36 months. Compared with historical controls, resectional surgery appears to offer benefit to selected patients with pulmonary disease caused by M. tuberculosis with extensive levels of drug resistance. PMID- 2106812 TI - Oxygen radical-dependent bacterial killing and pulmonary hypertension in piglets infected with group B streptococci. AB - The mechanism by which bacteria are cleared by the pulmonary circulation and the relation of this process to development of hemodynamic abnormalities are not understood. This study tested the hypotheses that clearance of Group B Streptococcus (GBS) during transit through the pulmonary circulation of infant piglets is related to oxygen radical-dependent bacterial killing and that killing of the organism is linked to development of pulmonary hypertension. GBS were radiolabeled with 111In and infused intravenously for 15 min (10(8) organisms/kg/min) into infant piglets ranging in age from 5 to 14 days. Lung specimens were excised at termination of the GBS infusion or 45 min thereafter, and both the relative deposition and viability of the bacteria were determined. The percentage of infused GBS recovered in lung tissue did not differ between the two time points (26 +/- 7% versus 29 +/- 8%), but the relative viability at termination of the infusion, 50 +/- 11%, was reduced to 19 +/- 4% within 45 min. Treatment with an oxygen radical scavenger, dimethylthiourea (DMTU), failed to influence the pulmonary deposition of GBS but significantly increased viability of the organism from 21.4 +/- 2.6 to 33.3 +/- 5.3%. As expected, GBS infusion was accompanied by pulmonary hypertension and arterial hypoxemia; DMTU attenuated these responses by 52 and 78%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106813 TI - Protein kinase C influences rat pulmonary vascular reactivity. AB - To test the role of protein kinase C in the control of pulmonary vascular tone and reactivity, we examined the effects of the activators, phorbol 12-myristate 13-acetate (PMA), mezerein, and 1,2-dioctanyl-rac-glycerol (1,2-DOG), in rat isolated large pulmonary arteries and salt solution-perfused lungs. PMA (500 nM) and mezerein (100 nM) induced slow, sustained contractions of isolated pulmonary arteries. These contractions were not inhibited by nifedipine (1 microM), the intracellular Ca2+ blocker TMB-8 (50 microM), a 0 Ca2+ and EGTA (2 mM) bath, or endothelial denudation. They were reduced by amiloride (500 microM), an inhibitor of Na+/H+ exchange, and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7); (50 microM), an inhibitor of protein kinase C. PMA caused concentration-dependent (5 to 500 nM) potentiation of KCl, serotonin, and A23187 contractions of isolated pulmonary arteries. The effect of PMA on norepinephrine contraction was dependent on both concentration and time. Whereas PMA potentiated norepinephrine contraction after 5 min, it inhibited the response after 60 min. PMA and mezerein also caused concentration-dependent (0.5 to 500 nM) vasoconstriction in isolated lungs. The PMA vasoconstriction was unaltered by meclofenamate (1.6 microM) but was attenuated by nifedipine (1 microM). Low concentrations of PMA (5 nM) and 1,2 DOG (50 microM) potentiated both hypoxic and KCl vasoconstriction in isolated lungs. In contrast, the hypoxic and KCl responses were blunted by H-7 (30 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106814 TI - Developmental changes in the response of the newborn to sustained ventilatory elastic loads. AB - Postnatal development of the steady-state response to inspiratory elastic loading was studied in eight 48-h-old and eight 24-day-old unanesthetized, tracheostomized monkeys. Both age groups exhibited a fall in minute ventilation (VE) with loads of two to five times baseline respiratory elastance. There was no statistical difference in the ventilatory response between age groups. The response patterns of both groups were characterized by a fall in both tidal volume (VT) and mean inspiratory flow (VT/TI) associated with a prolongation of TI and TI/Ttot. All subjects demonstrated a significant load compensatory response both in terms of neural drive (diaphragmatic EMG output) and force output (inspiratory work production). Arterial CO2 increased significantly during loading in the older subjects in linear correlation with the decline in VE, but the newborns did not exhibit a statistically significant alteration in PaCO2 throughout the range of elastic loads. These data indicate that normal newborns are capable of responding to an external elastic load and that the newborn response is comparable to that of more mature subjects. PMID- 2106815 TI - The ventilatory recruitment threshold for carbon dioxide. AB - We report our initial experience with a technique with which the chemoresponsiveness of the respiratory controller can be characterized in terms of an inspiratory on-switch threshold to CO2. After suppression of phasic respiratory muscle activity by mechanical ventilation, a CO2 recruitment threshold (PCO2RT) was defined as the lowest alveolar CO2 tension at which CO2 supplementation to inspired gas caused a reappearance of inspiratory efforts. Because PCO2RT can be determined in the absence of a mechanical load on the ventilatory pump, respiratory system mechanics and inspiratory muscle function should not influence the measurement itself. Thus, this technique may be helpful to study ventilatory requirements and load responses in critically ill patients with respiratory failure. We have shown that inspiratory muscle recruitment can be equally well-inferred from changes in the airway pressure and flow tracings during mechanical ventilation, from the pattern of chest wall displacement, and from the integrated diaphragm electromyogram. Within a subject, PCO2RT is a reproducible measurement that is not influenced by ventilator settings and end expiratory lung volume, provided that phasic respiratory muscle has been suppressed prior to CO2 supplementation. Details of the methodology, the likely determinants of PCO2RT, and the clinical utility of this technique are discussed. PMID- 2106816 TI - A 62-dose, 6-month therapy for pulmonary and extrapulmonary tuberculosis. A twice weekly, directly observed, and cost-effective regimen. AB - STUDY OBJECTIVE: To evaluate the efficacy and toxicity of a 62-dose, four-drug, 6 month, and directly observed regimen for treatment of pulmonary and extrapulmonary tuberculosis. DESIGN: An open, nonblinded clinical trial, with intended follow-up of patients for 36 months after the completion of therapy. SETTING: A metropolitan tuberculosis clinic in a public health department. PATIENTS: From March 1981 through April 1989, we enrolled 160 patients with suspected or known tuberculosis; 35 of these patients were excluded from the analysis. INTERVENTIONS: Isoniazid, rifampin, pyrazinamide, and streptomycin were administered daily for 2 weeks; these drugs were then given in higher doses twice weekly for 6 weeks, followed by isoniazid and rifampin twice weekly for 6 weeks, followed by isoniazid and rifampin twice weekly for 18 weeks. A total of 62 doses were administered, and all therapy was directly observed by a nurse or an outreach worker. MEASUREMENTS AND MAIN RESULTS: Of the 125 evaluable patients, 101 (81%) had pulmonary tuberculosis, 7 (6%) had both pulmonary and extrapulmonary involvement, and 17 (13%) had extrapulmonary disease only. Seventy one (57%) patients had a history of recent alcoholism. There were two relapses (1.6% +/- 2.2%), occurring 6 and 56 months after the completion of therapy. The time at which sputum samples became culture negative in pulmonary patients ranged from 1 to 19 weeks (median, 4.6 weeks); 40% +/- 9.6% of patients were culture negative after 4 weeks of therapy, 75% +/- 8.5% after 8 weeks, 94% +/- 4.7% after 12 weeks, 97% +/- 3.3% after 16 weeks, and 100% after 20 weeks. Adverse drug reactions included hyperuricemia (greater than 178 mumol/L [3 mg/dL] above normal) secondary to pyrazinamide in 80 patients (64%), twofold or greater elevations of aspartate aminotransferase in 21 patients (17%), 1.5-fold or greater elevations of alkaline phosphatase in 33 patients (27%), cutaneous abnormalities in 8 patients (6%), nausea in five patients (4%), and dizziness in 1 patient (1%). CONCLUSIONS: This 62-dose, largely twice-weekly tuberculosis treatment regimen is efficacious and relatively nontoxic and is especially useful for patients in whom directly observed therapy is indicated. PMID- 2106817 TI - Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. AB - Monoclonal immunoglobulin deposition occurs in tissues as Congo Red binding fibrils in light chain amyloidosis, as less structured deposits in light chain deposition disease, and as similar but distinct deposits in light and heavy chain deposition disease. The nonamyloid forms were found in 13 patients who had evidence of plasmacytic dyscrasia by the immunohistochemical detection of immunoglobulin light chains of kappa or lambda class (with or without staining for a single heavy chain isotype) and by the absence of amyloid P component in tissue sections that did not show the birefringence characteristic of amyloid after Congo Red staining. All but two of the patients presented with proteinuria with or without azotemia. Clinical syndromes involving other organ systems were less common but occasionally severe. Four patients had overt multiple myeloma. Three others had hypercalcemia and mild bone marrow plasmacytosis but no lytic lesions. Analyses of immunoglobulin synthesis in bone marrow cells from seven patients showed excess light chains in all and incomplete light chains or heavy chain fragments in six, regardless of whether an intact monoclonal protein or related subunit was in the serum or urine. The fibrillar (amyloidotic) and nonfibrillar forms of monoclonal immunoglobulin deposition occur either in overt multiple myeloma or in the course of less neoplastically aggressive plasmacytic dyscrasias. Bone marrow cells from patients with either type produce immunoglobulin fragments that are related to those deposited in the affected tissues. PMID- 2106818 TI - Parenteral nutrition and cancer chemotherapy. PMID- 2106819 TI - Topical flurbiprofen in intraocular surgery on diabetic and nondiabetic patients. AB - Effects of topical flurbiprofen, a highly potent prostaglandin synthetase inhibitor, were evaluated during planned extracapsular cataract extraction in diabetic and nondiabetic patients. One drop of flurbiprofen 0.1% or vehicle solution was instilled preoperatively and three times a day postoperatively for seven days. Pupil size was measured at several stages throughout and after the operation. Further, intraocular pressure before and after the operation was compared. In the nondiabetic patients, aqueous cells and flare, cells in the vitreous body, and pericorneal injection were examined as postoperative inflammatory responses. In the nondiabetic patients pupillary constriction was significantly suppressed by flurbiprofen at the end of anterior capsulotomy (P less than .05) and at the end of surgery (P less than .01). In the vehicle group, postoperative reduction in intraocular pressure was significant compared with that of the flurbiprofen group. These effects were not found in the diabetic patients. Inflammatory responses were not suppressed in the flurbiprofen group compared with the control group except for pericorneal injection. PMID- 2106820 TI - In search of pathologic correlates for hearing loss and vertigo in Paget's disease. A clinical and histopathologic study of 26 temporal bones. AB - Mixed sensorineural and conductive hearing loss is a common clinical manifestation of Paget's disease of the temporal bone, and while there are numerous clinical and pathologic reports on the condition, none have identified a consistent pathologic explanation for the hearing loss. We performed histologic studies on 26 temporal bones exhibiting Paget's disease from 16 persons, of whom 7 had audiometric testing performed. Contrary to common opinion, the conductive hearing loss is not caused by ossicular fixation; in fact, no cause could be found in the seven ears with documented conductive hearing losses. While the sensorineural hearing losses were greater than normal for age, we could not identify cochlear disorders that could be attributed to Paget's disease. It is concluded that the hearing losses in Paget's disease are caused by changes in bone density, mass, and form that serve to dampen the finely tuned motion mechanics of the middle and inner ears. PMID- 2106821 TI - Combined single day 14C-triolein breath test and PABA test in the diagnosis of malabsorption. AB - The 14C-triolein breath test, a recognised index of fat absorption, and the p aminobenzoic acid (PABA) test, a 'tubeless' test of exocrine pancreatic function, have both been widely used in the diagnosis of malabsorption and exocrine pancreatic insufficiency. This study evaluates the potential of a combination of both tests in the investigation of fat absorption and exocrine pancreatic function. Combination of the tests has become technically feasible because of the introduction of high pressure liquid chromatography as the preferred method of analysis for PABA, and use of p-aminosalicylic acid (PAS) as the marker for PABA absorption and metabolism. We studied 25 healthy subjects, 11 patients with exocrine pancreatic disease and 12 patients with gastrointestinal disease. The combined test identified subjects with reduced fat absorption and distinguished subjects with exocrine pancreatic insufficiency from those with an intestinal cause of fat malabsorption. The test could be completed in 7 h and had high patient acceptability. These findings suggest that the combined 14C-triolein breath test and PABA test can be used as a non-invasive, 1-day investigation of fat absorption and exocrine pancreatic function. PMID- 2106822 TI - In vitro stability of assayed renin activity in plasma and whole blood. PMID- 2106823 TI - Variation in plasma apolipoprotein A-1 and B concentrations following myocardial infarction. AB - Measurements of plasma apolipoprotein A-1 and B concentrations are increasingly used for the laboratory assessment of risk of coronary artery disease (CAD). This study of 22 patients investigated the response of plasma apolipoprotein A-1 and B levels for up to 20 days following a myocardial infarction. Seven of these patients participated in a clinical trial using the drug Tissue Plasminogen Activator (TPA). We established that, unlike many other plasma proteins, apolipoproteins do not display a classic acute phase response following myocardial infarction, although large variations in plasma apolipoprotein levels were observed in the patients investigated. Our studies also show that the measurement of plasma apolipoproteins A-1 and B to assess future CAD risk in myocardial infarction patients should be deferred for a minimum of at least 14 days post-infarction. No significant difference was observed in the pattern of apolipoprotein response between patients receiving TPA and those not given this drug. PMID- 2106824 TI - Transduction of linked chromosomal genes between Pseudomonas aeruginosa strains during incubation in situ in a freshwater habitat. AB - Both transduction of single chromosomal loci and cotransduction of closely linked loci were observed between lysogenic and nonlysogenic strains of Pseudomonas aeruginosa in a freshwater habitat. Transductants were recovered at frequencies of 10(-6) to 10(-5) transductants per CFU. Transductants of lysogenized strains were recovered 10- to 100-fold more frequently than were transductants of nonlysogenic parents. Lysogens are thus capable of introducing phages which mediate generalized transduction into the natural microbial community and serving as recipients of transduced DNA. It would appear that lysogeny has the potential of increasing the size and flexibility of the gene pool available to natural populations of bacteria. The ability to generate and select new genetic combinations through phage-mediated exchange can be significant in the face of a continually changing environment and may contribute to the apparent fitness of the lysogenic state in natural ecosystems. PMID- 2106825 TI - Selective plating medium for quantitative recovery of food-borne Listeria monocytogenes. AB - A new plating medium (lithium chloride-ceftazidime agar [LCA]) was designed to quantitatively recover food-borne Listeria monocytogenes in the form of large colonies while inhibiting most other food-borne microorganisms. This medium included brain heart infusion agar as the nutritive agar base and a combination of selective agents (LiCl, glycine anhydride, and ceftazidime). Comparison of LCA and lithium chloride-phenylethanol-moxalactam agar (LPM) indicated that both were equally effective for the enumeration of the cold-tolerant pathogen in artificially and naturally contaminated foods. However, LCA was more effective than LPM in the recovery of sublethally heat-injured cells. Moreover, Listeria colonies on LCA exhibited a more distinct bluish hue than those on LPM when viewed by the Henry oblique transillumination technique. PMID- 2106826 TI - Construction and applications of DNA probes for detection of polychlorinated biphenyl-degrading genotypes in toxic organic-contaminated soil environments. AB - Several DNA probes for polychlorinated biphenyl (PCB)-degrading genotypes were constructed from PCB-degrading bacteria. These laboratory-engineered DNA probes were used for the detection, enumeration, and isolation of specific bacteria degrading PCBs. Dot blot analysis of purified DNA from toxic organic chemical contaminated soil bacterial communities showed positive DNA-DNA hybridization with a 32P-labeled DNA probe (pAW6194, cbpABCD). Less than 1% of bacterial colonies isolated from garden topsoil and greater than 80% of bacteria isolated from PCB-contaminated soils showed DNA homologies with 32P-labeled DNA probes. Some of the PCB-degrading bacterial isolates detected by the DNA probe method did not show biphenyl clearance. The DNA probe method was found to detect additional organisms with greater genetic potential to degrade PCBs than the biphenyl clearance method did. Results from this study demonstrate the usefulness of DNA probes in detecting specific PCB-degrading bacteria, abundance of PCB-degrading genotypes, and genotypic diversity among PCB-degrading bacteria in toxic chemical polluted soil environments. We suggest that the DNA probe should be used with caution for accurate assessment of PCB-degradative capacity within soils and further recommend that a combination of DNA probe and biodegradation assay be used to determine the abundance of PCB-degrading bacteria in the soil bacterial community. PMID- 2106827 TI - New screening test to determine the acceptability of 0.45-micron membrane filters for analysis of water. AB - During routine membrane filter (MF) quality control testing, irregularities such as partial or complete inhibition of microbial growth at grid lines, abnormal spreading of colonies, growth in or along the grid lines, nonwetting areas, poor colony sheen and metallic sheen on the MF surface with mEndo agar, brittleness, decreased recovery, and severe wrinkling were observed with several lots of filters. To study these effects and to develop a more sensitive screening test for MF quality, we compared five different MFs with various types and degrees of defects by using five stock coliform cultures and five different media. Results showed that the Enterobacter aerogenes-tryptic soy agar test system detected more MF defects than any other combination did and was superior to the Escherichia coli-mFC agar American Society for Testing and Materials method for grid line inhibition. Filtered natural samples grown on the same media showed the same effects as were observed with the pure cultures. Poor colony sheen and sheen on the MF surface were best detected with Enterobacter aerogenes on mEndo agar. The use of tryptic soy agar and mEndo agar with this organism permitted the maximum detection of MF irregularities. Of the 142 MF lots tested by this method, 30% were acceptable, 10% were marginally acceptable, and 61% were unacceptable. This method provides a valuable screening test for determining the acceptability of 0.45-microm-pore-size MFs used for coliform and heterotroph analysis and may also be useful in conjunction with other methods. PMID- 2106828 TI - Membrane lipid composition, fluidity, and surface charge changes in response to growth of the fresh water cyanobacterium Synechococcus 6311 under high salinity. AB - The effect of adaptation to saline growth of a fresh water cyanobacterium Synechococcus 6311 on components of the cytoplasmic membranes and thylakoids was investigated. Significant changes in membrane surface charge, lipid, fatty acid, and carotenoid composition were observed upon transfer of the cells from a low salt (0.015 M NaCl) to a high salt (0.50 M NaCl) growth medium. Very similar changes in the polar lipid classes and fatty acid composition were observed in both membranes, but changes in fluidity and surface charge and a significant shift in the protein to lipid ratio were only apparent in the cytoplasmic membranes. The fluidity and surface charge data correlate well with functional studies and we can attribute the cytoplasmic membrane as the major site of interaction and adaptation to the saline environment. PMID- 2106829 TI - A particle concentration fluorescence immunoassay for prostaglandin D synthase in the rat central nervous system. AB - A solid phase, particle concentration fluorescence immunoassay (PCFIA) was developed for the measurement of prostaglandin (PG) D synthase in the 100,000g supernatant of various regions of the rat central nervous system. In this assay, the enzyme (in the range of 1-25 micrograms protein of brain supernatant or 1-100 ng of the purified enzyme) is attached to submicrometer carboxypolystyrene beads coated with polyclonal anti-rat brain PGD synthase IgG. The total particle-bound enzyme is assayed with fluorescein isothiocyanate (FITC)-conjugated monoclonal anti-PGD synthase IgG after incubation for 1 h. The optimum assay condition was obtained when carboxyl particles coated with ca. 500 micrograms/ml of polyclonal IgG at pH 5.0 and 5 micrograms/ml of FITC-IgG were used. No significant fluorescence was observed when FITC conjugates or carboxyl particles were prepared using IgG from nonimmunized rabbits. Heat treatment of the brain supernatant decreased the specific binding of the enzyme in parallel with the loss of enzyme activity, indicating that the denatured enzyme is not recognized by this assay method. The PGD synthase immunoreactivity was widely distributed in the brain regions and was highest in the paraflocculus. Although slight discrepancy was observed between the concentration by PCFIA and the enzyme activity measured by using [14C]PGH2 in some brain regions, there is a considerable correlation (0.727) between the values by both methods in the same brain regions. The PCFIA now developed showed higher sensitivity (around 10 times), greater reliability, and larger number of samples measurable at once than the radio-TLC assay using [14C]PGH2. This method could provide valuable information concerning the regulatory mechanisms of PGD synthase. PMID- 2106830 TI - Effect of brief treatment at alkaline pH on the properties of UDP glucuronosyltransferase. AB - The kinetic properties of UDP-glucuronosyltransferase were measured after brief treatment of liver microsomes at alkaline pH, followed by assay with p-nitro phenol as aglycone, at pH 7.5. Enzyme activity increased in a graded fashion as the pH of pretreatment was increased above 8.0, with apparent maximal activation of eight-fold for a pretreatment pH of 11.1. The pH for half maximal activation was 10.6. Brief treatment at alkaline pH prior to assay at pH 7.5 was associated too with a graded conversion of the kinetics of the enzyme from non-Michaelis Menten to Michaelis-Menten at pH 11.7. Sensitivity to the allosteric modulator, UDP-N-acetylglucosamine decreased as the pH increased. A fifty percent loss of sensitivity to UDP-N-acetylglucosamine-induced activation occurred at pH 10.6. Thus, pretreatment at alkaline pH had irreversible effects on the properties of UDP-glucuronosyltransferase in microsomes. In order to establish the cause for the irreversibility of the changes induced by alkaline pH, microsomes were treated at pH 11.6 prior to purifying UDP-glucuronosyltransferase. Enzyme purified from alkali-treated and untreated microsomes had approximately the same specific activity. More importantly, responses to activation by lipids, and regeneration of allosteric properties were the same for both purified enzymes (from alkali-treated and control microsomes). Pure enzyme was not activated by pretreatment at alkaline pH. We interpret these data to mean that the irreversible effects of alkaline pH on the properties of UDP glucuronosyltransferase in microsomes were not due to direct effects on the enzyme, but to how the enzyme interacted normally with molecules within the plane of the membrane. PMID- 2106831 TI - Tetrahydrohomofolate polyglutamates as inhibitors of thymidylate synthase and glycinamide ribonucleotide formyltransferase in Lactobacillus casei. AB - In order to determine the mechanism for the effects of homofolates on growth of Lactobacillus casei, polyglutamated derivatives of homofolate (HPteGlu), dihydrohomofolate and tetrahydrohomofolate (H4HPteGlu) were synthesized and tested as inhibitors of folate-requiring enzymes. The following L. casei enzymes were examined: thymidylate synthase (TS), glycinamide ribonucleotide formyltransferase (GARFT), aminoimidazolecarboxamide ribonucleotide formyltransferase, serine hydroxymethyltransferase and dihydrofolate reductase. Polyglutamates of (6R,S)-H4HPteGlu are potent inhibitors of TS and GARFT. For example, the IC50 values of (6R,S)-H4HPteGlu6 are 0.7 microM for TS and 0.3 microM for GARFT. By contrast, the value for HPteGlu6 is greater than 10 microM for both TS and GARFT. Inhibition of TS and GARFT by (6R,S)-H4HPteGlu derivatives increases with polyglutamate chain length. For TS, the Glu5 and Glu6 derivatives of (6R,S)-H4HPteGlu are 20 and 30 times more potent than the monoglutamate, respectively. For GARFT, the Glu2-6 derivatives are 2-3 times more potent than Glu1. Inhibition of TS and GARFT by (6R,S)-H4HPteGlu polyglutamates is almost entirely due to the unnatural (6R) diastereomer at C-6. Homofolate derivatives are only weak inhibitors of aminoimidazolecarboxamide ribonucleotide formyltransferase, serine hydroxymethyltransferase, and dihydrofolate reductase. We conclude that both TS and GARFT are potential targets of (6R)-H4HPteGlu polyglutamates. PMID- 2106832 TI - Partial characterization of proteoglycans synthesized by human glomerular epithelial cells in culture. AB - Confluent adult and fetal human glomerular epithelial cells were incubated for 24 h in the presence of [3H]-amino acids and [35S]sulfate. Two heparan-35SO4 proteoglycans were released into the culture medium. These 35S-labeled proteoglycans eluted as a single peak from anion exchange chromatographic columns, but were separable by gel filtration on Sepharose CL-6B columns. The larger heparan-35SO4 proteoglycan eluted with the column void volume and at a Kav of 0.26 from Sepharose CL-4B columns. The most abundant medium heparan-35SO4 proteoglycan was a high buoyant density proteoglycan similar in hydrodynamic size (Sepharose CL-6B Kav 0.23) to those previously described in glomerular basement membranes and isolated glomeruli. Heparan-35SO4 chains from both proteoglycans were 36 kDa. A smaller proportion of Sepharose CL-6B excluded dermatan-35SO4 proteoglycan was also synthesized by these cells. The predominant protein cores of both medium heparan-35SO4 proteoglycans were approximately 230 and 180 kDa. A hybrid chondroitin/dermatan-heparan-35SO4 proteoglycan with an 80-kDa protein core copurified with the smaller medium heparan-35SO4 proteoglycan. This 35S labeled proteoglycan appeared as a diffuse, chondroitinase ABC sensitive 155-kDa fluorographic band in sodium dodecyl sulfate-polyacrylamide gels after the Sepharose CL-6B Kav 0.23 35S-labeled proteoglycan fraction was digested with heparitinase. The heparitinase generated heparan sulfate proteoglycan protein cores and the 155-kDa hybrid proteoglycan fragment had molecular weights similar to those previously identified in rat glomerular basement membrane and glomeruli using antibodies against a basement membrane tumor proteoglycan precursor (Klein et al. J. Cell Biol. 106, 963-970, 1988). Thus, human glomerular epithelial cells in culture are capable of synthesizing, processing, and releasing heparan sulfate proteoglycans which are similar to those synthesized in vivo and found in the glomerular basement membrane. These proteoglycans may belong to a family of related basement membrane proteoglycans. PMID- 2106833 TI - Differential regulation of hepatic carbonic anhydrase isozymes in the streptozotocin-diabetic rat. AB - Most work with the male rat liver carbonic anhydrase isozymes in the past decade has centered on the cytosolic CA III and the mitochondrial CA V. This paper reports that the relative activity of both isozymes is altered in streptozotocin diabetes. Carbonic anhydrase activity of perfused liver homogenates and disrupted, isolated mitochondria was measured by the mass spectrometric 18O decay technique at 37 degrees C. The contributions of the different isozymes were determined based on intracellular location and sensitivity to acetazolamide inhibition. Diabetes resulted in a twofold increase in the activity of CA V but a halving in the activity of CA III. This is the first time that liver CA V has been shown to be altered by physiological stress. The total carbonic anhydrase activity in the diabetic rat liver was unaltered compared with control rats; however, CA III never accounted for more than 50% of this activity. Since CA isozymes I, II, and IV together account for 30% of the CA activity in control rats and 70% in diabetic rats it is concluded that one or more of these isozymes is subject to regulation in the diabetic male rat. The increase in CA V during diabetes is in accord with this isozyme having an important function in provision of substrate for hepatic gluconeogenesis and ureagenesis. PMID- 2106834 TI - Anomerization and hydrolysis of lactose by beta-galactosidase from Saccharomyces lactis. AB - Beta-Galactosidase from Saccharomyces lactis was found to be able to catalyze both the anomerization of alpha-lactose and the hydrolysis of beta-lactose; the rate of hydrolysis appeared to be four times higher with a 1:1 mixture of alpha and beta lactose than with a freshly prepared solution of alpha-lactose. The enzyme was also found to be unable to hydrolyze alpha-lactose. Thus, it appears that beta-galactosidase from S. lactis has its hydrolytic activity on lactose adapted only to the naturally more abundant beta-lactose. PMID- 2106835 TI - [Neoadjuvant chemotherapy of far advanced gastric cancer--effect of preoperative chemotherapy by PMUE (CDDP, MMC, UFT, etoposide]. AB - Preoperative chemotherapy with CDDP, MMC, UFT and etoposide (PMUE) was performed on cases of far advanced gastric cancer whose curative resection was impossible. The therapy comprised 1-5 courses of either intravenous or arterial infusion, or intraperitoneal administration of CDDP 75 mg/m2, MMC 10 mg/body and Etoposide 50 X 3 mg/body at 3-week intervals in combined use of UFT 400 mg/body. The effect of the preoperative PMUE therapy was CR, PR, NC and PD in 0, 7, 1 and 0 cases, respectively, the rate of effectiveness being 88% (7/8). 5 of 7 cases with PR were operated on, 2 cases succeeded in curative resection, but 3 cases did not. Histological judgment of effects confirmed Grade II-a, II-b and III in 2, 2 and 1 cases, respectively; these 5 cases further received 1-4 courses of PMUE therapy as postoperative adjuvant chemotherapy and are still alive at P.S. 0-2, suggesting the great efficacy of this PMUE therapy as a neoadjuvant chemotherapy for improvement in prognosis in far advanced gastric cancer. Abnormally high values of the tumor marker were noted in 5 of 8 cases, 4 of which had tumor marker values lowered in exponential function by the preoperative chemotherapy, which constituted an effective index in determining chemotherapeutic effects and the determination of the operative timing. PMID- 2106836 TI - [Effects of mesna (2-mercaptoethane sodium sulfonate) in children with malignant disease receiving oxazaphosphorine chemotherapy]. AB - We studied the efficacy of mesna as a protectant for urotoxicity in pediatric patients receiving chemotherapy including oxazaphosphorines. Nineteen patients with malignant diseases (5 neuroblastoma, 3 acute lymphocytic leukemia, 4 acute non-lymphocytic leukemia, 2 non-Hodgkin lymphoma, 3 osteosarcoma and 2 rhabdomyosarcoma) were treated with a total of 106 courses of therapy between June of 1986 and May of 1989. Of these, no gross hematuria were seen. Microhematuria transiently occurred only in 2 courses (5%) of 1 patient (2%). These data indicated that mesna was highly effective for urotoxicity of oxazaphosphorines without any side effects, especially in pediatric patients. PMID- 2106837 TI - [Evaluation of UFT administration in patients with ovarian cancer who had no evidence of disease after the initial therapy]. AB - Twenty nine patients with ovarian cancer of common epitherial origin who had no evidence of disease proved by computed tomography after the initial operation and chemotherapy were studied. The patients were randomized into two groups; (A) administration of UFT (1-(2-tetrahydrofuryl)-5-fluorouracil mixed with uracil) orally at a daily dose of 300 mg, 12 cases, (B) no further therapy, 17 cases. The therapeutic efficacy of UFT was assessed pathologically at the second look laparotomy (SLL). Plasma levels of 5-FU, tegafur and uracil were determined once a month to check whether patients intake UFT regularly or not. There were no significant difference in the mean age, in the distribution of numbers of patients in FIGO stage and histological cell type, in the mean total doses of CDDP and doxorubicin given at the initial chemotherapy [CDDP: (A) 352 +/- 152 mg, (B) 464 +/- 192 mg, doxorubicin: (A) 118 +/- 76 mg, (B) 119 +/- 92 mg] and in the duration between the initial operation and the SLL [(A) 484 +/- 154 days, (B) 414 +/- 274 days] between the two groups. The mean periods in the administration of UFT were 484.3 +/- 154 days. Recurrence was identified at the SLL in 1 case (8.3%) at paraaortic lymph nodes in (A) and 3 cases (17.6%) at the mesenterium, cul-de-sac and ascitic fluids in (B). No significant difference of recurrence ratio was observed between the two. Further long-term observation is required to assess the advantage of administration of UFT. PMID- 2106838 TI - Psoriasis induced at the injection site of recombinant interferon gamma. Results of immunohistologic investigations. AB - Recombinant human interferon gamma used for treatment of psoriatic arthritis was found to induce expression of HLA-DR, but not HLA-DP or HLA-DQ, on keratinocytes at the site of injection. Some patients showed an improvement of their joint symptoms, but the cutaneous manifestations remained unaffected. In 10 of 42 patients, punctiform psoriatic foci could be induced at the site of injection of interferon gamma. For this presentation, we selected a female patient with psoriatic arthropathy and type II diabetes mellitus in whom psoriasis was induced at the site of application of interferon gamma, but not after subcutaneous injection of insulin or placebo. We conclude that interferon gamma is an important lymphokine in the development of psoriasis. PMID- 2106839 TI - Induction of second trimester abortion by intraamniotic instillation of Rivanol (ethacridine) combined with oxytocin infusion. AB - We report our experience of 0.1% intraamniotic Rivanol in the interruption of 100 midtrimester pregnancies (15-24 gestation weeks). The mean injection to abortion interval was 37.2h and there were no complications. Intraamniotic Rivanol injection combined with oxytocin infusion seemed an effective and safe method for terminating second trimester pregnancies. PMID- 2106840 TI - Measuring performance in clinical rheumatology. PMID- 2106841 TI - Conservative treatment of early breast cancer. Long-term results of 1232 cases treated with quadrantectomy, axillary dissection, and radiotherapy. AB - One thousand two hundred and thirty-two women with invasive breast cancer lesions measuring less than 2 cm in diameter, clinically assessed as T1N0-1M0, were treated from 1970 to 1983 at the National Cancer Institute of Milan with quadrantectomy, axillary dissection, and radiotherapy (QUART). Pathologic evidence of lymph-nodes metastases was found in 32% of the patients. Overall survival at 5 and 10 years from surgery was 91% and 78%, respectively. The cumulative probability of survival tends to decrease with increasing tumor size: the 7-year survival rate was 84% in cases in which lesions measured from 1.6 to 2.0 cm, and 94% in cases in which the lesions were less than 0.5 cm. Tumor site in the treated breast did not affect distant outcome. No difference was found between the patients without node metastases and patients with one node involved, whereas the patients with more than one node showed a lower probability of survival. The survival curves of 352 cases treated inside a randomized trial and that of 880 cases routinely treated appear to be superimposable. Local recurrences and new primary ipsilateral tumors were, respectively, 35 (2.8%) and 19 (1.6%); 56 women with local recurrences or second tumors underwent second surgery (total mastectomy, 43; wide resection, 11). Five of them died from distant spread of breast cancer, while 49 are alive and well. In the contralateral breasts 45 carcinomas were recorded during the follow-up time. The results of the present analysis of a large number of T1 cases reconfirm the safety of integrated radiosurgical conservative treatments. PMID- 2106842 TI - Choledochoscopy. A cost-minimization analysis. AB - Although choledochoscopy for the prevention of retained bile duct stones has been postulated as cost effective, no economic evaluation exists to substantiate this claim. We performed a cost-minimization analysis on 287 patients who underwent choledochoscopy during operations for biliary tract calculi between 1981 and 1987 to assess the economic impact of choledochoscopy versus noncholedochoscopic alternatives in obtaining a stone-free duct. Common duct exploration was positive for calculi in 75% of patients. Choledochoscopy-detected residual stones after duct exploration in 10% of patients. Residual stones were more frequent after positive (12.5%) than negative (2.7%) duct explorations. retained stones occurred in 4.5% of patients after operation. Sensitivity, specificity, and negative predictive values of choledochoscopy were 67%, 100%, and 95%, respectively. Cost minimization analysis showed that total cost of either selective ($75,250) or routine ($110,450) choledochoscopy significantly exceeded the total cost of obtaining a stone-free duct for patients with retained stones via either extraction through a T-tube tract ($17,545) or by endoscopic papillotomy ($45,675). Because choledochoscopy was not economically competitive with noncholedochoscopic, nonoperative alternatives, reduction of choledochoscopy fees was implemented to economically justify continued use of choledochoscopy. We conclude that choledochoscopy is clinically efficacious in obtaining a stone-free duct, but endorsement of either routine or selective choledochoscopy by cost minimization analysis requires careful assessment of fee structure to make choledochoscopy competitive economically. PMID- 2106843 TI - What rate of infusion of intravenous nutrition solution is required to stimulate uptake of amino acids by peripheral tissues in depleted patients? AB - We examined the effect of varying the quantities (0, 0.1, 0.2, 0.3, and 0.4 gN.kg 1.[day]-1) of nitrogen input on N balance, 3-methylhistidine (3MH) excretion, plasma amino acid concentration and the net flux of amino acids across the leg in depleted patients requiring parenteral nutrition. The calorie-to-nitrogen ratio was 140 to 1 (kcal:1 gN) and consequently the patients received varying amounts of calories (8, 14, 28, 42, and 56 kcal.kg-1.[day]-10. There was negative nitrogen balance and net loss of amino acids from the limb during fasting. An infusion of 0.2 gN.kg-1.[day]-1 of IVN reversed the net catabolic process and resulted in equilibrium of peripheral total amino acid flux and of tyrosine flux without a decrease in 3MH excretion. Net uptake of total amino acids and tyrosine in peripheral tissues was achieved with 0.4 gN.kg-1.[day]-1 and 56 kcal.kg 1.[day]-1. This was associated with a fivefold increase in 3MH excretion (p less than 0.01), indicating that net anabolism occurred with increased protein turnover. Fifty per cent of the amino acids taken up by peripheral tissues during infusions of 0.4 gN.kg-1.[day]-1 was due to the uptake of glutamate (Glu) and 20% was due to the uptake of branched chain amino acids (BCAA). Plasma Glu concentration, [Glu], did not increase with increasing IVN infusion, but BCAA concentrations did. Although the mean plasma [Glu] did not change with IVN infusion, there was an independent effect of plasma [Glu] (p less than 0.0001) and of N input (p less than 0.0001) on Glu flux, indicating that even at high infusion rates the maximal capacity of peripheral tissues to take up Glu had not been reached. PMID- 2106844 TI - Serum enzyme levels during intestinal ischemia. AB - Because the intestinal mucosa is most sensitive to ischemia, serum levels of mucosal enzymes, such as diamine oxidase, may be most likely to indicate intestinal ischemia. Our aim was to compare serum levels of mucosal (diamine oxidase, alkaline phosphatase) and seromuscular (creatinine phosphokinase, lactic dehydrogenase, serum glutamic oxaloacetic transminase) enzymes during intestinal ischemia of varying extent and duration in dogs. Group 1 (n = 6) underwent sham laparotomy. Group 2 (n = 8) had 50% of the small intestine devascularized. Group 3 (n = 8) had the superior mesenteric artery occluded for 2 hours and released. Group 4 (n = 8) had the superior mesenteric artery ligated. Serum samples were obtained before and 2, 4, 8, and 24 hours after operation, and histologic specimens were examined at 4 hours. Creatinine phosphokinase levels became elevated within 4 hours of ischemic injury in group 2 (223 +/- 197 vs. 68 +/- 26, p less than 0.05) and group 4 (212 +/- 136 vs. 76 +/- 29, p less than 0.05). Significant elevation of serum enzymes levels, except diamine oxidase, occurred in groups 2, 3, and 4 at 24 hours, including those with normal histology after temporary superior mesenteric artery occlusion. Thus seromuscular enzymes, particularly creatinine phosphokinase, were more likely to be elevated during intestinal ischemia. Enzyme levels were not influenced by the extent and reversibility of the ischemic injury. PMID- 2106845 TI - Chemotherapy and radiation therapy before transhiatal esophagectomy for esophageal carcinoma. AB - Recent efforts to improve survival in patients with esophageal carcinoma have combined both systemic and local therapy. From October 1985 to October 1987, 43 patients with local-regional esophageal cancer (adenocarcinoma in 21, squamous cell in 22) were treated with cisplatin, vinblastine, and 5-fluorouracil chemotherapy concurrent with 4,500 cGy radiation therapy for 21 days before transhiatal esophagectomy 3 weeks later. Two patients died of chemotherapy/radiation therapy toxicity. Forty-one completed preoperative chemotherapy/radiation therapy. At operation, 2 patients had incurable metastatic disease; 39 underwent transhiatal esophagectomy. Eleven patients had no residual tumor in the resected specimen for a 27% (11 of 41) pathological complete response rate. Preoperative chemotherapy/radiation therapy resulted in no increased perioperative morbidity as compared with our historical controls. One patient died postoperatively of an unrecognized brain metastasis (2% operative morbidity). At a median follow-up of 27 months, 20 patients (47%) are alive and clinically disease-free and 21 have died, 19 from progression of their carcinoma. The median survival time for all 43 patients is 29 months (Kaplan-Meier estimate), and cumulative survival is 72% at 12 months, 60% at 24 months, and 46% at 36 months. All 11 patients with a complete response are alive at a median follow-up of 36 months, and all are disease-free. The 2-year survival of 60% of this group as compared with 32% in our earlier patients treated with transhiatal esophagectomy alone suggests that intensive combined modality therapy improves survival in these patients. A randomized prospective trial is now in progress. PMID- 2106846 TI - Prostaglandin E1 and intrapulmonary shunt in cardiac surgical patients with pulmonary hypertension. AB - Unlike many other vasodilators, prostaglandin E1 may reduce pulmonary vascular resistance without changing intrapulmonary shunt in patients with adult respiratory distress syndrome. Whether the same is true for surgical patients with cardiogenic pulmonary hypertension but normal gas exchange remains unclear. Data from the intraoperative records of 8 patients with pulmonary hypertension and elevated pulmonary vascular resistance were used for the study. Hemodynamic variables had been monitored through radial arterial cannulas and pulmonary arterial catheters. Arterial and mixed venous oxygen tension, carbon dioxide tension, oxygen saturation, and hemoglobin level, as well as cardiac output and pulmonary capillary wedge pressure, had been determined in each patient before prostaglandin E1 infusion was started and again when the desired pulmonary vascular response had been achieved. Pulmonary and systemic vascular resistances and intrapulmonary shunt were calculated from standard formulas. Infusion rates of prostaglandin E1 ranged from 7 to 135 ng/kg/min. Prostaglandin E1 reduced mean pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary capillary wedge pressure but did not change intrapulmonary shunt. Heart rate and mean arterial and right atrial pressures were not changed, whereas systemic vascular resistance decreased and cardiac output increased. The present study shows that prostaglandin E1 reduces pulmonary arterial pressure and pulmonary vascular resistance without dramatic changes in intrapulmonary shunt in patients with pulmonary hypertension secondary to cardiac disease. PMID- 2106848 TI - Benefits and burdens of tube feeding and physical restraints. PMID- 2106847 TI - Positive predictive value of clinical suspicion of abdominal aortic aneurysm. Implications for efficient use of abdominal ultrasonography. AB - Although selective screening for an abdominal aortic aneurysm (AAA) by abdominal palpation aimed at detecting AAAs has engendered considerable support, no population-based data pertaining to the positive predictive value (PPV) of the clinical assessment of AAAs in routine clinical practice are available. Therefore, we used the unique resources of the Rochester (Minn) Epidemiology Project and the Mayo Clinic computerized abdominal ultrasonography database to identify all residents of Olmsted County, Minnesota,who underwent ultrasound examination for a clinically suspected AAA between November 1, 1985, and October 31, 1987. Of 116 residents who were suspected of having an AAA on abdominal palpation and were referred for an ultrasound examination for confirmation, 17 patients had a 3.5-cm or greater AAA by ultrasound examination (PPV = 14.7%). The probability of AAA by ultrasound examination (PPV = 14.7%). The probability of AAA documentation by ultrasound examination given clinical suspicion of an AAA was associated with higher body mass index, older age,and presence of other macrovascular disease. In 17 patients aged 70 years or younger, without other macrovascular disease and with body mass index of 24 or less, only 1 had an AAA of 3.5 cm or greater (PPV = 6%), while 10 of 20 patients aged 70 years or older, with macrovascular disease,and with body mass index greater than 24 had an AAA of 3.5 cm or greater (PPV = 50%). These population-based data that highlight the poor PPV of the clinical assessment for AAAs indicate that abdominal palpation aimed at detecting AAAs as part of a periodic health examination may lead to a much higher rate of false-positive results than indicated by previous referral based data. Further research is needed to identify patient subgroups in whom abdominal palpation for detection of AAAs will be cost-effective with respect to reduction in AAA mortality. PMID- 2106849 TI - [Immediate or delayed angioplasty during the acute phase of myocardial infarction. Apropos of 118 cases]. AB - The results of immediate percutaneous transluminal coronary angioplasty (PTCA) (260 +/- 167 minutes after onset of pain and an average of 56 minutes after thrombolysis) and deferred PTCA (average 9.6 days, range 1 to 30 days after infarction) were compared in 118 consecutive patients with acute myocardial infarction. The overall primary success rate of PTCA was 82.2 per cent; it was higher in those patients undergoing deferred angioplasty (96% vs 78%; p less than 0.05). The primary success rate of immediate PTCA was related to the severity of the stenosis before dilatation: 75 per cent success in occluded compared to 84 per cent in suboccluded vessels (over 90% stenosis) and 100 per cent success in vessels with under 90 per cent stenosis. Eighty one per cent of failed angioplasties occurred in patients with occluded arteries, the majority being left anterior descending (LAD) arteries (71.4%). The incidence of restenosis was 13.4 per cent. This complication was diagnosed at coronary arteriography performed 40 days after PTCA in 1 case, 47 days after PTCA in another case and at the 6 month control in 11 cases. Reocclusion was observed in 21 patients (21.7% of immediate successes). The occlusion was diagnosed at the first control after an average of 8 days in 15 cases. The interval between the onset of pain and thrombolysis and dilatation was significantly longer in the group with reocclusion compared with patients without reocclusion (314 minutes vs 193 minutes for thrombolysis, p less than 0.01; and 356 minutes vs 204 minutes fort PTCA, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106850 TI - [Electrophysiology in evaluating the treatment of sustained monomorphic ventricular tachycardia: criteria for efficacy]. AB - The authors studied the influence on recurrence and mortality of induced ventricular arrhythmias during electrophysiological studies performed to assess the efficacy of treatment of sustained monomorphic ventricular tachycardia. One hundred and twenty-six consecutive patients investigated from 1981 to 1988 were included. The underlying pathology was chronic myocardial infarction (N = 56), dilated cardiomyopathy (N = 24), right ventricular dysplasia (N = 31) and there were 15 idiopathic cases. All these tachycardias could be induced during the control study. A second test was performed after instituting treatment. This was maintained whatever the result of the electrophysiological study except in patients in whom the tachycardia rate was over 130/mn and/or poorly tolerated. Recurrences were defined as the observation of tachycardia with the same morphology and/or the occurrence of sudden death. Follow-up averaged 29 +/- 21 months. The absence of recurrence and survival were assessed by the Kaplan-Meier method and Logrank's test. It was not possible to induce any arrhythmia after treatment in 52 patients (41%). The prevalence of absence of recurrence in this group was 0.863. If the induction of ventricular fibrillation, doublets or short runs of VT (N less than 6 with no recurrences) are included, the value increased to 0.877. These patients were considered to be non-inducible. The prevalence of absence of recurrence of arrhythmia in patients in whom it was possible to induce sustained ventricular tachycardia of the same morphology as the clinical arrhythmia was 0.512 (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106852 TI - [Mid-term results of 50 percutaneous aortic valvuloplasties. Follow-up studies using Doppler echocardiography]. AB - The aim of this study was to assess the results of percutaneous aortic valvuloplasty in 50 patients (29 men and 21 women, mean age 74 years) at 6 months by Doppler echocardiography performed 24 hours before, 24 hours, 3 and 6 months after the procedure. The following parameters were compared: maximum instantaneous transaortic pressure gradient; mean gradient; aortic valve area and index of valve patency. The initial results of catheterisation and valvuloplasty were very satisfactory as the peak-to-peak and mean pressure gradients decreased by 50 per cent and the aortic valve area increased from 0.55 +/- 0.2 to 0.83 +/- 0.30 cm2 and the success rate defined as a final surface area greater than 0.75 cm2 was 84 per cent. Unfortunately, these favourable results were not sustained in most cases: restenosis, defined as a valve area of less than 0.7 cm2, was observed in 18 per cent of patients at Day 1 and 71 per cent of patients at the 6th month; the natural history of disease was little affected with a global mortality rate at 6 months of 18 per cent through cardiac failure and sudden death; only 18 per cent of patients maintained an aortic valve area of over 0.75 cm2 at 6 months. These results suggest that percutaneous aortic valvuloplasty should be reserved for patients in whom surgery is formally contra-indicated. PMID- 2106851 TI - [Early reocclusion after in situ coronary desobstruction either with streptokinase or angioplasty during the acute phase of myocardial infarction]. AB - The aim of this study was to assess the incidence of early reocclusion after therapeutic reperfusion of coronary arteries in acute myocardial infarction. Seventy four patients underwent intracoronary thrombolysis and 133 patients had immediate coronary angioplasty. The success rates were 70 per cent and 86 per cent respectively (p less than 0.01) and the degree of residual stenosis was 77 +/- 13 percent and 25 +/- 15 per cent respectively (p less than 0.001). The patients in whom coronary reperfusion was successful, 52 after in situ thrombolysis, 48 after angioplasty alone, and 66 after combined angioplasty and intravenous thrombolysis, underwent coronary arteriography 24 to 36 hours later. Reocclusion was asymptomatic in 46 per cent of cases (13/28) and its prevalence was 16.9 per cent: 25.5 per cent for the right coronary compared with 12.8 per cent for the left anterior descending (p less than 0.05) and 11.7 per cent for the left circumflex artery; reocclusion occurred in 8.6 per cent of patients treated before the 3rd hour compared with 22.9 per cent of patients receiving treatment after the 3rd hour (p less than 0.05). The incidence of reocclusion was 17.3 per cent after intracoronary thrombolysis and 16.7 per cent after angioplasty (angioplasty alone 18.7 per cent; associated with thrombolysis 15.2%). The degree of residual stenosis was nil after intracoronary thrombolysis and 16.3 per cent after angioplasty when the stenosis was insignificant, and 20.5 per cent and 18.8 per cent respectively with stenotic lesions greater than 50 per cent. PMID- 2106853 TI - [Efficacy and safety of ambulatory coronary angiography]. AB - Ambulatory coronary arteriography was carried out in 160 patients in the first 18 months' activity of our department (9.5% of all cardiac catheterisations and 16% of all coronary arteriographies during the same period). An absolutely stable clinical condition was the main criterion of selection for this investigation and the protocol consisted in day hospital admission, absence of routine anticoagulation, small calibre (5 French = 1.7 mm) catheters, mobilisation 4 hours and discharge 6 hours after the procedure. The patients were 38 women and 122 men whose average age was 55 years. The percutaneous femoral approach was used in most cases (95%). Single or multiple coronary artery disease was documented in 55 per cent of these patients: there were 2 cases of left main stem stenosis. Eight patients required full hospital admission, mainly because of the severity of the coronary lesions. Minor complications occurred in 2 per cent of cases. These results indicate that ambulatory coronary arteriography is safe, effective and economic. It could be used more extensively always providing that the contra-indications are respected. PMID- 2106854 TI - [Value of negative U waves in coronary artery spasm]. AB - The significance of U-wave inversion during coronary arterial spasm was investigated in 188 consecutive ergometric tests performed in 69 patients. All patients had previously undergone coronary arteriography which had clearly shown coronary spasm either at rest or after a single 0.4 mg injection of ergometrine. The ergometrine tests were then performed at the patient's bedside using a standard protocol with injection of incremental doses of ergometrine: 0.05, 0.1, 0.2 and 0.4 mg every 5 minutes with 12-lead ECG recordings every minute. Fifty of the 59 patients with positive tests had classical signs of spasms: ST elevation or depression and/or T wave inversion; the other 9 patients had inversion of the U wave alone (2 cases) or associated with classical ST segment changes in the remaining cases. The 10 other patients had no ECG changes although 2 of them suffered typical anginal pain. Negative U waves were observed in 4 of the 12 patients with spasm of the left anterior descending artery, accompanied by ST elevation in the anterior wall leads. A negative U wave would appear to be a sign of less ischaemia than the classical ECG changes because anginal pain is less common: 4 out of 9 cases in which U wave inversion was a very early change, 8 out of 9 cases in which it was the first or only abnormality. The recognition of a negative U wave increases the sensitivity of the electrocardiogram during resting angina and allows earlier treatment of coronary spasm with nitrate derivatives after an ergometrine test. PMID- 2106855 TI - [Results of thrombo-endarterectomy of chronic pulmonary embolism]. AB - Between 1973 and 1987, 33 patients underwent pulmonary thromboendarterectomy for chronic pulmonary embolism. Twenty-six patients were in Class III of the NYHA Classification, 5 in Class IV with overt right ventricular failure and 2 in Class II. The average pO2 was 60 mmHg under basal conditions without oxygen therapy. The amputation of the pulmonary vascular tree was greater than 50 per cent in all patients. The average systolic pulmonary artery pressure was 70 mmHg. Twenty patients were operated by a lateral thoracotomy without CPB and 6 by sternotomy with CPB under normothermia with or without cardiac fibrillation. The later method avoids having to open the pleura and seemed to give better haemodynamic control. Interruption of the inferior vena cava was systematic in all cases. The global operative mortality was 20 per cent but this seemed to be less in the patients operated by sternotomy under normothermic CPB (no deaths in 6 patients). The authors consider that this technique should be studied in a larger series of patients. Eighteen patients are still being followed up; the clinical and scintigraphic and/or angiographic improvement is clearcut in the majority of cases. PMID- 2106856 TI - [Heart and heart-lung transplantation. 3 years' experience in Timone CHU (Marseilles 1985-1988)]. AB - Since December 1985, we have performed 38 transplantations: cardiac (CT) n: 31, cardiopulmonary (CPT) n: 1, or bipulmonary (BPT) n: 6. There were 31 male and 7 female patients, aged 7 to 62, mean 46. In the cardiac group, the cardiomyopathy was primitive in 13, ischemic in 16, valvular in 2. Five patients had undergone one or more previous operations. Three patients had a biventricular assist device (1,6 and 7 days before transplant) for acute cardiac failure. The indication of CPT or BPT was pulmonary artery hypertension (1), silicosis (1), cystic fibrosis (4). There were 4 post-operative deaths in the CT group (12.9%); failure of graft, low cardiac output, pulmonary artery hypertension by multiple pulmonary thrombosis, and 2 deaths in the CPT and BPT groups (28%). The mean post-operative hospital stay was one month. All patients with CT were treated by an initial maintenance bitherapy protocol (cyclosporine, steroids) and observed by myocardial biopsies and echocardiograms. In 40 per cent of the patients, Azathioprine was subsequently added. The patients had 2.1 rejection episode/patient/year, either spontaneously reversed of treated medically. There were two late deaths (2 and 7 months) by refractory rejection. 78 per cent of the patients were alive one year after transplant. All survivors have recovered a normal life, some of them with full-time work.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2106857 TI - [Total anomalous pulmonary venous connection. Results of repair in 50 infants]. AB - Fifty infants with isolated total anomalous pulmonary venous connection (TAPVC) were operated between 1/01/73 and 31/12/87. The average weight at surgery, which was performed under hypothermia with circulatory arrest in 92 per cent of cases, was 4.5 Kg. The preoperative pulmonary to systemic pressure ratios (PAP/PS) enabled identification of two groups of patients: Group I: TAPVC without severe pulmonary hypertension (PAP/PS less than 0.85) (n = 35), and Group II: TAPVC with severe pulmonary hypertension (PAP/PS greater than 0.55) (n = 15). The hospital mortality was 22 per cent (8 cases) in Group I compared with 73 per cent (11 cases) in Group II (p less than 0.05). Patients in Group II were younger (64 days compared with 137 days, p less than 0.02), lighter (p less than 0.05) and had preoperative mean pulmonary artery systolic pressures of 83 mmHg (p greater than 0.001). Three patients in Group I required early reoperation for stenosis of the pulmonary veins at the site of repair resulting in pulmonary hypertension, and all died. The global survival was 28 patients with an average follow-up of 7 years (range 1 to 15 years). Six of these patients were reoperated (2 phrenoplications, 4 atrial shunts). All survivors are asymptomatic and have no conduction defects. Control echocardiography in 15 of the 28 survivors was judged to be normal. These results show that obstructive forms of TAPVC (Group II) carry a very poor prognosis: immediate results in this group could only be improved by earlier surgery. The clinical long-term results in those who survive surgery are very satisfactory. PMID- 2106858 TI - [Dipyridamole echocardiography test during the acute phase of lower myocardial infarction]. AB - Two-dimensional echocardiography with intravenous injection of dipyridamole (0.56 mg/kg) was performed in 33 consecutive patients with acute (2 +/- 2 days) postero inferior myocardial infarction for semiquantitative segmental wall motion analysis. The results were compared with those of coronary angiography which was carried out during the hospital period. After a second evaluation of the recordings the following results were obtained: feasibility: 94 per cent with 85 per cent of segments analysed. Residual ischaemia in the first days of myocardial necrosis was common (70%). The ischaemia was often clinically silent including during the investigation (61%). When pain occurred, it always followed changes in regional wall motion. The dipyridamole test suggested multivessel disease with a sensitivity of 72 per cent and a specificity of 90 per cent, and residual arterial stenosis with a sensitivity of 75 per cent ans specificity of 80 per cent the secondary effects were minor. The main limitation of the test is related to the distinction between pharmacological and physiologic ischaemia. A positive test was associated with lesions justifying myocardial revascularisation (coronary bypass or angioplasty) in 19 out of 23 cases but with a very poor correlation with the topography of the coronary lesions. A negative test indicated arterial occlusion, residual stenosis with extensive myocardial damage or a normal coronary angiogram. Therefore, the dipyridamole echocardiography test may help identify a group of patients with little or no myocardial ischaemia in whom invasive investigations could be deferred; these patients contrast with the group with a positive test indicating residual ischaemia in which the coronary lesions should be documented by coronary angiography. PMID- 2106859 TI - [Exercise echocardiography and study of the left ventricle in sportsmen during exertion]. AB - The use of an original ultrasonic transducer holder has made possible the recording of M mode and 2D echocardiography during exercise. Left ventricular function was studied during upright bicycle exercise in two groups: 10 trained athletes (Group A) and 10 normal subjects (Group B). All were 20 years of age. Satisfactory echocardiograms were obtained up to a mean heart rate of 180/mn which corresponded to an average work load of 180 W in Group B and 300 W in Group A. The cardiac output was comparable in the two groups up to a 180 W load, but in Group A a lower HR was compensated by a larger stroke volume (SV). The increase in SV in Group A was related to a greater LV end-diastolic dimension (LVEDD) during exercise, whereas the ejection fraction increased less than in the control group. During very strenuous exercise (Group A only) further increases in cardiac output were related mainly to an increased heart rate and to a lesser degree to increased LVEDD and ejection fraction. PMID- 2106860 TI - [Noninvasive measurement of cardiac output by pulsed Doppler echocardiography. Correlation with thermodilution]. AB - Cardiac output was measured simultaneously by pulsed Doppler echocardiography and thermodilution in 22 patients, 18 of whom also underwent atrial pacing at different rates to give a total of 42 different measurements. The aortic diameter was measured firstly at the aortic ring at the level of insertion of the aortic cusps and then at the point of maximum separation of the valve cups in the left parasternal long-axis view. The aortic velocities were recorded in the apical 5 chamber view immediately below the level of the aortic valve. The correlations obtained at the aortic ring (R1) and at the point of maximum separation of the valve cusps (R2) were 0.77 (y = 0.67x + 1.17: standard error = 0.81 l/m) and 0.64 (y = 0.56x + 0.87; standard error = 1.01 l/mn) respectively. The correlations were much better when 7 technically unsatisfactory measurements were excluded (R2 = 0.76: y = 0.59x + 0.74: standard error = 0.79 l/mn) (R1 = 0.87: y = 0.72x + 1.04: standard error = 0.65 l/mn). THe correlations of stroke volume measured at aortic ring level also improved from r = 0.82 (y = 0.75x + 7.29: standard error = 8.9 ml) to r = 0.89 (y = 0.78x + 7.38: standard error = 7.3 ml). The measurement of cardiac output by pulsed Doppler echocardiography in the aortic root seems to be reliable. The correlations of the values of stroke volume and cardiac output with the thermodilution method are good, allowing detection of beat-to-beat variations of cardiac output, in suitable patients in the hands of experienced operators. PMID- 2106861 TI - [Determination of the ventilatory threshold during the exercise test in patients with cardiac insufficiency. Relation of the lactate threshold]. AB - The non-invasive assessment of the lactate threshold during exercise test is possible in normal subjects by the study of respiratory gas exchange: a ventilatory threshold may be determined using Wasserman's criteria. This determination is more unreliable in cardiac failure. Forty-four patients with cardiac failure underwent exercise tests with measurement of lactate concentrations and respiratory gas exchanges during the exercise. Despite a regular increase in the lactate concentration from the onset of exercise, it was possible to determine a lactate threshold in the majority of patients. A ventilatory threshold could be determined in 27 to 38 patients depending on the method used. The correlation between these two thresholds was excellent (r = 0.87). The determination of the ventilatory threshold during exercise is therefore possible in cardiac failure. The main limitation of the method is that no result can be obtained in a large number of patients (15 to 20%) which restricts its value as a principal method of therapeutic evaluation. PMID- 2106862 TI - [Vasomotor tonus and non-prostanoid endothelium-derived vasoactive factors]. AB - There are two types of non-prostanoid endothelium-derived vasoactive factors, one which relaxes and the other which contracts the vascular smooth muscle (EDRF and EDCF). These factors are released in response to stimulation of specific membrane receptors of the vascular endothelium by a large number of agonist substances and in response to physical stimuli to the vascular wall. It has been shown that EDRF is nitric oxide (NO) and EDCF has recently been identified as a peptide composed of 21 amino acids called endothelin. Other compounds may also act as EDRF or EDCF. EDRF (NO) induces relaxation of the underlying vascular smooth muscle by increasing intracellular concentration of cyclic guanosine monophosphate. The mechanisms of action of endothelin have not yet been clearly defined. It would seem that they depend, at least partially, on influx of extracellular calcium. The recent discovery of endothelin and the increased knowledge of the mode of action of EDRF on vascular smooth muscle has led to the suggestion that, vasomotor tone in humans is probably the result of an equilibrium between these two factors, each of which play a fundamental role, and very likely interact with each other in maintaining and regulating vascular tone in man. PMID- 2106863 TI - [Post-traumatic fistula of the left anterior descending coronary artery and left ventricle. Apropos of a new case]. AB - The authors report the case of a 23 year old man who presented with a continuous murmur five years after closed chest trauma. The electrocardiographic and echocardiographic findings indicated previous apical myocardial infarction. The underlying diagnosis was first suggested by continuous wave Doppler which showed systolo-diastolic flow in the septo-apical region directed towards the left ventricle (LV) in diastole. Color Doppler flow studies showed a mosaic pattern opposite a dilated left anterior descending (LAD) artery. These signs of LAD-LV fistula with a single orific were confirmed at coronary arteriography. The patient's previous history was in favour of a traumatic etiology. In the absence of left ventricular failure and myocardial ischaemia by coronary steal, surgery was deferred; Doppler echocardiography would seem to be a good method of following up the fistula and its consequences on left ventricular function. A traumatic left coronary to left ventricular fistula is an extremely rare condition and merits publication. The authors review the literature and describe the physiopathology, diagnosis and therapeutic indications of these fistulae. PMID- 2106864 TI - [Localized dilatation of the bronchi. A misunderstood etiology of coronaro bronchial fistula]. AB - The authors report the case of a coronary to bronchial artery anastomosis secondary to focal bronchiectasis. The diagnosis was made after finding large retroatrial vessels on coronary arteriography. A pulmonary steal syndrome, frequently reported in this condition in the literature, was not present in that particular case. The diagnosis of a coronary to bronchial artery anastomosis should alert the physician to possible underlying cardiac disease (Tetralogy of Fallot, supravalvular aortic stenosis, severe coronary artery disease). A bronchopulmonary etiology (chronic obstructive airways disease, multiple bullae, bronchiectasis) is less commonly found as the presentation is often atypical. PMID- 2106865 TI - [Unilateral left agenesis of the pericardium. Contribution of cardiac imaging]. AB - The authors report a case of congenital absence of the left pericardium in a pauci-symptomatic young woman. Indirect signs in favour of this diagnosis were elicited on chest X-ray (levoposition of the heart, convex left heart border). An associated congenital heart lesion was excluded by Doppler echocardiography. Computed tomography and MRI showed the right pericardium to be present but the left pericardium (not always visible in normal subjects) and the pre-aortic recess (present in all normal subjects) were absent. Abnormal presence of lung tissue between the aorta and pulmonary artery, and also between the pulmonary artery and left auricle was, however, confirmed. Nevertheless, these investigations did not enable the authors to define the exact extent of the pericardial defect. Finally, the indirect signs of levocardioposition were the main diagnostic markers of congenital absence of the left pericardium which did not require surgery in this particular case. PMID- 2106866 TI - [The fundamental problems and evaluation criteria for rational imaging diagnosis in oncology]. AB - The increasing number of imaging procedures in the oncological diagnostics requires the rational and economic reasonable use of these methods. To avoid an "overdiagnosis" due to the use of multiple expensive methods for the same diagnostic problem, precise information about the cost-benefit-risk relations are necessary and should be available for radiologists, oncologists and other authorities. The aim is to receive a fast and more reliable diagnosis with lower risk and burden for the patients in reasonable expense. As a result may be the reduction of less effective outmoded methods. This paper formulates basic considerations which can be used for further more detailed and intensive investigations for establishing a rational diagnosis. PMID- 2106867 TI - Collagen species in various sized human arteries and their changes with intimal proliferation. AB - The collagen types extracted from intermediate and small sized human arteries were investigated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) after differential salt fractionation. Limited and repeated pepsin digestion was used to prepare collagen species. Type V, IV and VI collagens were extracted greater in the former relative to in the latter, whereas type I and III collagen were extracted until the last extract. Type I collagen comprised as the major collagen in the intima of various arteries as well as in venous tissue. Type III and V collagens were found to be less in small arteries than in the initial stage of atherosclerosis. Type VI collagen in the intermediate and small arteries was detected on SDS-PAGE. PMID- 2106868 TI - Depression, anxiety, and temporal lobe epilepsy. Laterality of focus and symptoms. AB - The association between anxiety, depression, and lateralization of an epileptogenic focus was explored in 18 adult patients with a left temporal lobe focus, 21 with a right focus, 20 with bilateral temporal foci, and 16 individuals with absence seizures. No significant difference in the level of anxiety was found among the groups. However, patients with left-sided temporal lobe epilepsy scored significantly higher than other groups on self-ratings for depression. This could not be accounted for by factors such as duration of epilepsy, employment status, education, age at seizure onset, or medication status. The left temporal lobe epilepsy group had a nonsignificantly larger number of males and left-handed subjects. The possible interactions between gender, handedness, seizure focus, and vulnerability to depression are described. PMID- 2106869 TI - Paroxysmal nocturnal dystonia presenting as excessive daytime somnolence. AB - We describe the clinical and electrophysiologic findings in seven patients referred for evaluation of excessive daytime somnolence. These patients had none of the usual causes of excessive daytime somnolence but during sleep exhibited stereotypic body movements, tachycardia, respiratory disturbances, somniloquy, and transient arousals in a repetitive fashion. These episodes induced fragmentation of sleep. The polysomnograms revealed an increase in wakefulness and stage I decreased rapid eye movement during sleep in addition to the episodes of abnormal body movements. No epileptiform features were present either in the electroencephalogram or in the nocturnal polysomnogram. Four of the seven patients were treated with anticonvulsants, with both subjective and objective improvement on subsequent follow-up polysomnograms. Because of the pronounced functional deficits associated with the sleep disorder in these patients, it is of great importance to recognize the disorder and treat it appropriately. PMID- 2106870 TI - Retinal findings in the fat overload syndrome. PMID- 2106871 TI - Bovine retinal explants cultured in collagen gels. A model system for the study of proliferative retinopathy. AB - We have developed a model system for studying proliferative retinopathy in vitro using bovine retinal explants cultured in collagen gels. Cellular outgrowth from retinal explants occurred after 7 days as single cells from peripapillary explants or as cell sheets and tubular outgrowths from peripheral retinal explants. Single cell outgrowths were shown immunohistochemically to be endothelial cells or macrophages; sheetlike and tubular outgrowths also constituted cords of endothelial cells with stromal macrophages, but in addition glial cells were closely associated with the endothelial cells. Cellular outgrowths were preceded by extensive macrophage activation within the ischemic retinal explant, suggesting that macrophage-derived angiogenic factors may be important in inducing retinal endothelial cell proliferation. In addition, glial cell-derived factors may have a role in the development of vessellike tubular structures from endothelial cell outgrowths. PMID- 2106872 TI - Glaucoma filtration surgery in monkeys using 5-fluorouridine in polyanhydride disks. AB - We performed filtration surgery in glaucomatous monkeys to determine if bioerodible polyanhydride disks that contained 5-fluorouridine (5-FUR) prolonged the success of the operation. First, in vitro studies demonstrated that 5 fluorouridine was released from the disks for at least 16 days in a bioactive form that inhibited fibroblast proliferation. Next, a preliminary series of six eyes suggested that using disks that contained 5-fluorouridine extended the intraocular pressure-lowering effect of filtration surgery. This finding was confirmed in eight additional eyes of four animals in which one eye received a disk with 5-fluorouridine and the other received a disk without the drug. The duration of success of the operation was significantly longer in the eyes that received polyanhydride with 5-fluorouridine (mean +/- SD, 26.0 +/- 9.2 days) than in the controls (8.5 +/- 4.0 days). The histologic findings of the experimental eyes correlated with their prolonged clinical success. PMID- 2106873 TI - Isolation and characterization of proteoglycans synthesized by mouse osteoblastic cells in culture during the mineralization process. AB - Proteoglycans in mineralized (0.5 M-EDTA/4 M-guanidinium chloride-extractable) and non-mineralized (4 M-guanidinium chloride-extractable) matrices synthesized by a mouse osteoblastic-cell line MC3T3-E1 were characterized at different phases of mineralization in vitro. Cell cultures were labelled with [35S]sulphate and either [3H]glucosamine or 3H-labelled amino acids. At the mineralization phase a large majority of proteoglycans were extracted with 4 M-guanidinium chloride (G extract), and at least five species of labelled proteoglycans were identified; dermatan sulphate proteoglycans (DSPG), apparent Mr approx. 120,000 and 70,000), heparan sulphate proteoglycans (HSPG, apparent Mr approx. 200,000 and 120,000) and DS chains with very little core protein. DSPGs weakly bound to an octyl Sepharose CL-4B column and HSPGs bound more tightly, whereas DS chains did not bind to the column. Amounts of labelled proteoglycans extracted with 0.5 M-EDTA/4 M-guanidinium chloride (EDTA extract) were much less than those in G extract. Although the predominant species in the EDTA extract were comparable with the DS or DSPGs in the G extract, none of them bound to octyl-Sepharose CL-4B, indicating their lack of hydrophobicity. At the nonmineralizing phase a large chondroitin sulphate proteoglycan (Mr greater than 600,000) was found in the matrix in addition to the five proteoglycan species similar to those at the mineralization phase. Although DS chains at the early phase were similar in size to those at the mineralization phase, the ratio of 2-acetamido-2-deoxy-3-O-(beta D-gluco-4-enepyranosyluronic acid)-4-O-sulpho-D-galactose to 2-acetamido-2-deoxy 3-O-(beta-D-gluculo-4-enepyranosyluronic acid)-6-O-sulpho-D-galactose was less than that at the mineralization phase. These results agree with those of previous studies performed in vivo and suggest that alteration in the synthesis of proteoglycans is involved in the mineralization process. They also suggest that at the osteoblastic mineralization front proteoglycans undergo partial degradation and lose their hydrophobicity. PMID- 2106874 TI - Expression of extracellular superoxide dismutase by human cell lines. AB - Extracellular superoxide dismutase (EC-SOD) is the major SOD isoenzyme in extracellular fluids, but occurs also in tissues. The sites and characteristics of the synthesis of the enzyme are unknown. The occurrence of EC-SOD in cultures of a large panel of human cell lines was assayed by means of an e.l.i.s.a. Unlike the situation for the intracellular isoenzymes CuZn-SOD and Mn-SOD, expression of EC-SOD occurs in only a few cell types. None of the ten investigated suspension growing cell lines produced EC-SOD. Among normal diploid anchorage-dependent cell lines, expression was found in all 25 investigated fibroblast cell lines, in the two glia-cell lines, but not in six endothelial-cell lines, two epithelial-cell lines or in two amnion-derived lines. Among neoplastic anchorage-dependent cell lines expression was found in 13 out of 29. EC-SOD was secreted into the culture medium by cell lines expressing the enzyme. The rate of EC-SOD synthesis varied by nearly 100-fold among the fibroblast lines and remained essentially constant in the individual lines during long-term culture. In the nine investigated cases, the secreted EC-SOD was of the high-heparin-affinity C type. It is suggested that tissue EC-SOD is secreted by a few well-dispersed cell types, such as fibroblasts and glia cells, to diffuse subsequently around and reversibly bind to heparan sulphate proteoglycan ligands in the glycocalyx of the surface of most tissue cell types and in the interstitial matrix. PMID- 2106875 TI - A heart mitochondrial Ca2(+)-dependent pore of possible relevance to re-perfusion induced injury. Evidence that ADP facilitates pore interconversion between the closed and open states. AB - The permeability properties of a putative Ca2(+)-activated pore in heart mitochondria, of possible relevance to re-perfusion-induced injury, have been investigated by a pulsed-flow solute-entrapment technique. The relative permeabilities of [14C]mannitol, [14C]sucrose and arsenazo III are consistent with permeation via a pore of about 2.3 nm diameter. Ca2+ removal with EGTA induced pore closure, and the mitochondria became 'resealed'. The permeability of the unresealed mitochondria during resealing was markedly stimulated by 200 microM-ADP, and the relative permeabilities to solutes of different size were stimulated equally, indicating an increase in open-pore number, rather than an increase in pore dimensions. This is paradoxical, since ADP also stimulated the rate of resealing. The rate of EGTA-induced resealing was also stimulated by the Ca2+ ionophore A23187, which indicates that the rate of removal of matrix free Ca2+ is limiting for pore closure. An explanation for the paradox is suggested in which ADP facilitates pore interconversion between the closed and open states in permeabilized mitochondria, and pore closure in Ca2(+)-free mitochondria occurs much faster than previously thought. PMID- 2106876 TI - Characterization and localization of progesterone 5 alpha-reductase from cell cultures of foxglove (Digitalis lanata EHRH). AB - Progesterone 5 alpha-reductase, which catalyses the reduction of progesterone to 5 alpha-pregnane-3,20-dione, was isolated and characterized from cell cultures of Digitalis lanata (foxglove). Optimum enzyme activity was observed at pH 7.0, and the enzyme had an apparent Km value of 30 microM for its substrate progesterone. The enzyme needs NADPH as reductant, which could not be replaced by NADH. For NADPH, the apparent Km value is 130 microM. The optimum temperature was 40 degrees C; at temperatures below 45 degrees C, the product 5 alpha-pregnane-3,20 dione was reduced by a second reaction to 5 alpha-pregnan-3 beta-ol-20-one. Progesterone 5 alpha-reductase activity was not dependent on bivalent cations. In the presence of EDTA, 0.1 mM-Mn2+ had no influence on enzyme activity, whereas 0.1 mM-Ca2+, -Co2+ and -Zn2+ decreased progesterone 5 alpha-reductase activity. Only 0.1 mM-Mg2+ was slightly stimulatory. EDTA and thiol reagents such as dithiothreitol stimulate progesterone 5 alpha-reductase activity. By means of linear sucrose gradient fractionation of the cellular membranes, progesterone 5 alpha-reductase was found to be located in the endoplasmic reticulum. PMID- 2106877 TI - Hepoxilin A3 induces changes in cytosolic calcium, intracellular pH and membrane potential in human neutrophils. AB - The effects of hepoxilin A3 (HxA3), a 12-lipoxygenase metabolite of arachidonic acid, on cytosolic calcium ([Ca2+]i), intracellular pH (pHi), transmembrane potential and right-angle light scattering in human neutrophils were investigated. A rapid, transient elevation of [Ca2+]i was observed with HxA3 which was dependent on the concentration used. The effect of HxA3 on [Ca2+]i was blocked by pertussis toxin, suggesting involvement of receptors coupled to GTP binding proteins. Experiments in Ca2(+)-free medium and using intracellular Ca2+ chelators indicated that HxA3 mobilized Ca2+ from intracellular stores. At similar concentrations, HxA3 altered pHi, producing an initial acidification followed by an alkalinization. The initial acidification was decreased in cells loaded with a Ca2+ chelator. In the presence of N-ethyl-N-(1-methylethyl)amino amiloride, an inhibitor of the Na+/H+ antiport, HxA3 induced a greater acidification but failed to elicit the recovery phase, suggesting that the latter is due to activation of the antiport. HxA3 also depolarized the membrane potential, although this effect was small. A decrease in right-angle light scattering, qualitatively similar to that observed with chemotactic peptides, was seen with HxA3, indicating that the 12-lipoxygenase metabolite can induce shape changes in neutrophils. At the concentrations used for the above effects, HxA3 was unable to generate a respiratory burst. These findings suggest that hepoxilins, which are formed by stimulated neutrophils, may have a role as messengers in neutrophil activation. PMID- 2106878 TI - The amino acid sequence of chymopapain from Carica papaya. AB - Chymopapain is a polypeptide of 218 amino acid residues. It has considerable structural similarity with papain and papaya proteinase omega, including conservation of the catalytic site and of the disulphide bonding. Chymopapain is like papaya proteinase omega in carrying four extra residues between papain positions 168 and 169, but differs from both papaya proteinases in the composition of its S2 subsite, as well as in having a second thiol group, Cys 117. Some evidence for the amino acid sequence of chymopapain has been deposited as Supplementary Publication SUP 50153 (12 pages) at the British Library Document Supply Centre, Boston Spa., Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms indicated in Biochem. J. (1990) 265, 5. The information comprises Supplement Tables 1-4, which contain, in order, amino acid compositions of peptides from tryptic, peptic, CNBr and mild acid cleavages, Supplement Fig. 1, showing re-fractionation of selected peaks from Fig. 2 of the main paper. Supplement Fig. 2, showing cation-exchange chromatography of the earliest-eluted peak of Fig. 3 of the main paper, Supplement Fig. 3, showing reverse-phase h.p.l.c. of the later-eluted peak from Fig. 3 of the main paper, and Supplement Fig. 4, showing the separation of peptides after mild acid hydrolysis of CNBr-cleavage fragment CB3. PMID- 2106879 TI - Inhibition of lysophospholipase by cholesterol in rabbit aorta. AB - Lysophospholipase activity was measured in rabbit aorta using 1-[1-14C]palmitoyl sn-glycero-3-phosphocholine as a substrate. The enzyme did not require Ca2+ for its activation and the maximal activation was attained in the presence of EGTA. Cholesterol dose-dependently inhibited the lysophospholipase activity in the soluble fraction and IC50 value was approximately 15 microM. Lineweaver-Burk plot revealed that cholesterol competitively inhibited lysophospholipase and Km values in the presence and absence of cholesterol (15.5 microM) were 12.3 and 2.8 microM, respectively. Vmax values were approximately 475 pmol/min.mg. The results suggest that cholesterol can interact with the enzyme per se, resulting in the inhibition of the lysophospholipase activity in rabbit aorta. PMID- 2106880 TI - Conserved N-terminal sequences in the flagellins of archaebacteria. AB - Methanococcus voltae produces two flagellins of molecular weight 31,000 and 33,000. Amino acid analysis as well as peptide mapping with cyanogen bromide, chymotrypsin and Staphylococcus aureus V-8 protease indicates that the two flagellins are distinct. N-terminal sequencing of the 31,000 Mc. voltae flagellin as well as the 24,000 and 25,000 molecular weight flagellins of Methanospirillum hungatei GP1 shows an extensive homology with the reported N-terminus of the flagellins from Halobacterium halobium, deduced from the nucleotide sequence of the cloned genes. However, the N-termini of all three sequenced methanogen flagellins lack a terminal methionine and start at position 13 from the N terminus of H. halobium flagellins. This initial 12 amino acid stretch may be a leader peptide which is subsequently cleaved to generate the mature flagellin, which could suggest flagellar assembly in archaebacteria occurs by a mechanism distinct from that in eubacteria. The high degree of conservation of the N terminus of the flagellins from Mc. voltae, Msp. hungatei and H. halobium suggests an important role for this sequence, and that the archaebacteria share a common mechanism for flagellar biosynthesis. PMID- 2106881 TI - Inhibition of protein kinase C by H-7 potentiates the release of oleic, linoleic and arachidonic acids in A23187-stimulated human neutrophils. AB - This present report describes the effect of H-7, a protein kinase C inhibitor, on the release of oleic, linoleic and arachidonic acids in A23187-stimulated neutrophils. Surprisingly, the inhibitor potentiated the release of all three unsaturated fatty acids in neutrophils stimulated with A23187 alone. In contrast, released oleic acid, linoleic acid and arachidonic acid in phorbol 12-myristate 13-acetate-primed neutrophils were attenuated by 35, 47 and 33%, respectively, in the presence of H-7 (300 microM). Phorbol 12-myristate 13-acetate (PMA) had no effect on A23187-stimulated release of saturated fatty acids. Both PMA and H-7 when used alone had no effect on the release of saturated or unsaturated fatty acids. We, therefore, conclude that H-7 may have effects other than inhibiting PMA-primed responses including superoxide generation, degranulation and arachidonic acid release in human neutrophils. PMID- 2106882 TI - ADP-ribosylation of the rho/rac proteins induces growth inhibition, neurite outgrowth and acetylcholine esterase in cultured PC-12 cells. AB - Botulinum ADP-ribosyltransferase C3 (C3 exoenzyme) was purified to homogeneity and added to cultured rat pheochromocytoma PC-12 cells. Incubation with this exoenzyme caused inhibition of cell growth and induced neurites as well as acetylcholine esterase in these cells. These changes were dependent on the amount of the enzyme added to the culture, which correlated with the in situ ADP ribosylation of the rho/rac proteins in the cells. Preincubation with a specific anti-C3 exoenzyme monoclonal antibody inhibited both the ADP-ribosyltransferase activity and the neurite-inducing activity of the enzyme preparation. These results suggest that C3 exoenzyme affected the cellular function of the rho/rac proteins by ADP-ribosylation to induce these changes in the cells. PMID- 2106883 TI - The hepatic biosynthesis of rat thyroxine binding globulin (TBG): demonstration, ontogenesis, and up-regulation in experimental hypothyroidism. AB - Using a human thyroxine binding globulin (TBG) cDNA probe, we demonstrate that rat liver contains two TBG mRNA species of different length, consisting of about 1.8 Kb and 2.4 Kb respectively. Slot blot analysis of the hepatic mRNAs from rats of different age reveals a fair correlation between the developmental trend of the messengers and that of the TBG circulating levels. Finally Northern blot and slot studies demonstrate that the increase of serum TBG induced in adults by thyroidectomy actually reflects an enhanced hepatic biosynthesis of the protein. PMID- 2106884 TI - N-terminal domain of pepsin as a model for retroviral dimeric aspartyl protease. AB - Autolysis of porcine pepsin at pH 4 affords a derivative possessing intrinsic proteolytic activity. This derivative was isolated by alumina pseudo-affinity chromatography and gel-filtration and was found to result from the tight association of two identical molecules, 135 amino acids long, emerging from the N terminal domain of pepsin. This finding emphasizes a similarity with the only aspartyl-proteases known to act as dimers, the retroviral proteases. PMID- 2106885 TI - Activity and distribution of protein kinase C in liver during the acute-phase response. AB - Activity and subcellular distribution of protein kinase C were estimated in liver cytosol and membrane fractions of rats carrying a turpentine-induced inflammation. Protein kinase C activity increases significantly 8 h after treatment in the membrane fraction, with concurrent reduction in the cytosol; 10 h after treatment the membrane-associated activity returns to normal, without concomitant recovery of that detected in the cytosol. The specific binding of phorbol dibutyrate to the liver membrane fraction increases but overall the effect is less evident and delayed in time. The changes are associated to alterations in the phosphorylation pattern of some liver proteins. Liver protein kinase C activity and intracellular distribution seem to be affected by a treatment which is known to induce an acute-phase response in the liver cells. PMID- 2106886 TI - Synthetic analogs of growth hormone-releasing factor with antagonistic activity in vitro. AB - Analogs of human and rat growth hormone-releasing factor (hGRF and rGRF), related to [D-Arg2]hGRF(1-29)NH2, were synthesized by solid phase methodology. Their capacity to inhibit growth hormone secretion stimulated by hGRF(1-44)NH2 was tested on rat anterior pituitary cells in monolayer culture. Among the analogs of hGRF, [D-Arg2,29,Arg30]hGRF(1-30)NH2 showed the highest antagonistic potency of 3.64 relative to [D-Arg2]hGRF(1-29)NH2 = 1. However, the most potent analog synthesized thus far was [N-Ac-His1,D-Arg2,Ala15]rGRF(1-29)NH2, which showed a relative potency of 27.7. PMID- 2106887 TI - Chemical modification of the recombinant human alpha A- and beta-interferons. AB - Chemical modification has been used to map the residues essential for the antiviral activity of the recombinant human alpha A- and beta-interferons. Modification of His residues with diethylpyrocarbonate and N alpha-tosyl-L-lysyl chloromethylketone does not inhibit both interferons, whereas N alpha-tosyl-L phenylalanyl chloromethylketone significantly suppressing the activity of beta interferon does not affect the activity of alpha A-interferon. After the modification of 1, 2 and 3 Lys residues from 11 ones with 3-(2 pyridyldithio)propionic acid N-hydroxy-succinimide ester alpha A-interferon reveals 100%, 50% and 10% of the initial activity, respectively. Modification of Trp residues with H2O2, 2-nitrobenzenesulfenyl chloride or 2-hydroxy-5 nitrobenzylbromide inactivates alpha A- and beta-interferons completely. Presumably Trp residue(s) is essential for the antiviral activity of alpha- and beta-interferons. PMID- 2106888 TI - Arachidonic acid and its metabolites in the regulation of G-protein gated K+ channels in atrial myocytes. PMID- 2106889 TI - Effect of hypoglycemic sulfonylurea, glibenclamide, on the rate of catecholamine synthesis in cultured adrenal chromaffin cells. PMID- 2106890 TI - Once-daily ethosuximide in the treatment of absence epilepsy. AB - Once-daily ethosuximide was used to treat 10 consecutive children with typical absence seizures. Three patients had gastrointestinal side effects which resolved when the same total daily dose was divided into 2 doses. Two other patients continued to have seizures on ethosuximide, whether given once or twice daily. Five patients had complete seizure control without adverse effects on once-daily ethosuximide. PMID- 2106891 TI - Feeding tubes: maintaining life or stalling death? The nurse's role. PMID- 2106892 TI - Tube feeding problems and solutions. AB - This article discusses the uses of nasoenteral tubes, pre - during, and post tube feeding nursing care, medication administration through nasoenteral tubes, and possible tube feeding complications. Practical nursing techniques are provided. PMID- 2106893 TI - ["The emphasis should be with the chronic patient"]. PMID- 2106894 TI - [Obfuscation of costs in hospitals]. PMID- 2106895 TI - [10 years NVSPV (Netherland Society for Sociopsychiatric Nurses). The symposium, or: the future]. PMID- 2106896 TI - [10 years NVSPV. A present, or: the COOSPV (Central Organ Education for Sociopsychiatric Nurses)]. PMID- 2106897 TI - [100 years of TvZ. Introduction: with the first volume. 1890]. PMID- 2106898 TI - [100 years of TvZ. Introduction: with the 100th volume]. PMID- 2106899 TI - [CBO "Assessment study of the year". Assessment oral hygiene awarded a prize]. PMID- 2106900 TI - [Assessment oral hygiene. CBO's assessment study of the year]. PMID- 2106901 TI - Comparison of the properties of glucoamylases from Rhizopus niveus and Aspergillus niger. AB - Some properties of the glucoamylase from Rhizopus niveus have been determined and compared with the comparable properties of the glucoamylase from Aspergillus niger. The enzymes from these organisms possess the following common properties: quantitative conversion of starch to glucose, molecular weights in the range 95,500 to 97,500, and glycoprotein structures with many oligosaccharide side chains attached to the protein moieties of the enzymes. Differences in the glucoamylases exist in electrophoretic mobility, amino acid composition, nature of carbohydrate units, and types of glycosidic linkages. Lysine, threonine, serine, glutamic acid, tyrosine, and phenylalanine differ in the two glucoamylases by 25 to 50%. Whereas the enzyme from R. niveus contains mannose and glucosamine, in the N-acetyl form, as the carbohydrate constituents, the enzyme from A. niger contains mannose, glucose, and galactose. The carbohydrate chains of the R. niveus enzyme are linked by O-glycosidic and N-glycosidic linkages to the protein, while those of the A. niger enzyme are linked by O glycosidic linkages only. Antibodies directed against the two glucosamylases have been isolated by affinity chromatography and found to be specific for the carbohydrate units of the glucoamylases. Cross reactions did not occur between the glucoamylases and the purified antibodies. PMID- 2106902 TI - Crosslinked fibrous collagen for use as a dermal implant: control of the cytotoxic effects of glutaraldehyde and dimethylsuberimidate. AB - Collagen intended for use as a dermal implant may be crosslinked to increase its strength and persistence in vivo. Sheets of rat fibrous dermal collagen were crosslinked with either glutaraldehyde or dimethylsuberimidate and the cytotoxicity to human dermal fibroblasts resulting from these treatments was measured by following the inhibition of [3H]leucine incorporation into protein. Both agents were cytotoxic at the concentrations required to effect adequate crosslinking (0.005% and 25 mM, respectively). This cytotoxicity could be limited by extensive washing and by incubation with 5 mM L-lysine, with 66 mM (0.25% w/v) sodium borohydride, or with 71.3 mM (1% w/v) dimedone. However, cytotoxicity was most efficiently controlled by treatment with a combination of 66 mM sodium borohydride and 5 mM L-lysine or 66 mM sodium borohydride and 71.3 mM dimedone. [3H]Leucine incorporation by cells exposed to crosslinked collagen treated with these combinations approached 100% of the values recorded with cells exposed to uncrosslinked collagen. PMID- 2106904 TI - Possible lymphocyte effects on lactase expression by mouse jejunal enterocytes. AB - Jejunal intraepithelial lymphocyte numbers fall and lactase activity increases during early infection with the intestinal parasite Nematospiroides dubius. Both these variables later return to values found in control mice. These results support the view that local immune reactions, suppressed by the presence of N. dubius, normally inhibit lactase expression by mouse enterocytes. PMID- 2106903 TI - Acute valproic acid overdose. Clinical course and pharmacokinetic disposition of valproic acid and metabolites. AB - Acute toxicity in the setting of valproic acid (valproate sodium) overdose is in most cases benign and readily reversible. However, serious toxicity has been reported. We present a case of accidental acute valproic acid overdose in a 26 month-old female, in whom serious neurological, metabolic, haematological and respiratory sequelae occurred. The major toxicity observed was delayed cerebral oedema. We also present data not previously reported, which describes the pharmacokinetic disposition of valproic acid and several of its metabolites during the course of this acute overdose. A comparison of an enzyme immunoassay and gas liquid chromatographic methodologies for measuring valproic acid in this setting is also presented. It appears that the 2-EN-valproic acid metabolite plays a role in the neurological toxicity. PMID- 2106905 TI - Neuron-specific and state-specific differences in calcium homeostasis regulate the generation and degeneration of neuronal architecture. AB - Many stimuli (e.g., neurotransmitters and electrical activity) regulate neuromorphogenesis by changing intracellular calcium. The ionophore A23187 was employed as a receptor-independent method to investigate neuronal calcium homeostasis. Distinctive neuron-specific (B5 versus B19) and state-specific (growing versus non-growing) differences in calcium homeostasis were observed in cultured identified Helisoma neurons. Fura-2 studies revealed that A23187 induced a transient rise in intracellular calcium in growing neurons B5 but a sustained rise in growing neurons B19. In stable-state (non-growing) cells A23187 evoked only a transient calcium rise. Both neuron-specific and state-specific differences in calcium homeostasis were dependent on extracellular sodium. Morphological studies also indicated that such differences in calcium-regulatory capacity can have profound consequences on the generation and degeneration of neuronal architecture. PMID- 2106906 TI - Differential expression of amyloid precursor protein mRNAs in cases of Alzheimer's disease and in aged nonhuman primates. AB - Senile plaques are a characteristic feature in brains of individuals with Alzheimer's disease (AD) and aged monkeys. The principal component of amyloid in senile plaques is beta/A4, a peptide derived from a larger amyloid precursor protein (APP). To date, several alternatively spliced APP transcripts have been described. The relationship between levels of these APP mRNAs and amyloid deposition is unclear. In this study, we directly measured the relative levels of APP transcripts that lack the protease inhibitor domain (APP-695) and transcripts that encode the inhibitor sequences (APP-751/770). Our results indicate that the expression of APP mRNAs is not selectively altered in AD cortex. Moreover, the differential expression of APP transcripts is not correlated with the deposition of amyloid in cases of AD and aged monkeys. These findings suggest that other factors, not directly related to the relative expression of APP mRNAs, may contribute to amyloidogenesis in the brain. PMID- 2106907 TI - Interactions between antibiotics and antineoplastic drugs on antibacterial activity in vitro. AB - The effects of various combinations of antibacterial (ampicillin, cephadroxil, doxycycline, imipenem, trimethoprimsulfadiazine) and antineoplastic (cisplatin, epirubicin, mitoxantrone) drugs were evaluated in vitro with regard to antibacterial activity on five clinical isolates from cancer patients of respectively Escherichia coli, Staphylococcus aureus and Streptococcus faecalis. With one exception no significant effects on the bacterial growth were observed in the presence of the antitumor drug alone. In contrast, all five strains of Strept. faecalis grew better when mitoxantrone was included in a concentration of 0.1 mg/l. A synergistic action between imipenem and mitoxantrone was seen for single strains of Staph. aureus and E. coli. Furthermore, a dose-effect related inhibition by cisplatin on the growth of Strept. faecalis in the presence of sub MIC levels of trimethoprimsulfadiazine was observed. The study indicates that interaction between antibacterial and antineoplastic drugs is an erratic phenomenon, which has to be dealt with separately for each combination of drugs as well as for each bacterial strain. PMID- 2106908 TI - Differential excretion of xenobiotic acyl-esters of carnitine due to administration of pivampicillin and valproate. AB - The fate of supplemental carnitine was studied in human subjects treated with drugs known to cause carnitine deficiency. Six children were treated with pivampicillin and equimolar L-carnitine for 7 days. On the last day of treatment, the plasma levels of total and free carnitine were decreased, but acylcarnitine levels were increased. A 12-fold increase in urinary excretion of acylcarnitines was found; it increased from 188.5 +/- 82.7 to 2218.4 +/- 484.1 mumole/day, and 84% was pivaloylcarnitine. Free carnitine excretion was reduced. Ten epileptic children on chronic valproate treatment received equimolar carnitine for a 2-week period. Plasma carnitine levels were elevated on the last day of treatment. A 3.4 fold increase in urinary acylcarnitines was found, but most of the excreted carnitines were free (64.5-fold increases). These data show that pivalate is readily converted to carnitine esters, in contrast to the limited conversion of valproate to acylcarnitines in humans. PMID- 2106909 TI - Cyclosporin A modulation of the acute inflammatory response: an explanation for the effect of CsA on host defences in infection. AB - Previous studies have shown that the administration of cyclosporin A (CsA) to animals with experimentally induced pyelonephritis resulted in considerable exacerbation of infection. T-lymphocytes are not involved in the host response to pyelonephritis but neutrophils are known to be a key component in the pathogenesis of this infection, so the effect of CsA on this inflammatory component was investigated. CsA administration did not affect the metabolic activity of neutrophils in vitro nor their ability to phagocytose and kill microorganisms. However, the ability of neutrophils to mobilize to a sterile inflammatory focus in vivo was significantly impaired. Further experiments, using models of pyelonephritis and subcutaneous infection, demonstrated that the CsA induced suppression of neutrophil mobilization was directly related to the observed increase in bacterial numbers and exacerbation of tissue damage. Additionally, the actual effect of CsA on host defences and the outcome of infection was found to be dependent on the level of the initial infectious challenge. The results of this study provide an explanation for the current pattern of infectious disease in patients treated with CsA, in whom infection with extracellular pathogens is still common. It is also clear that the effect of CsA on inflammatory mechanisms may explain the efficacy of the agent in inflammatory diseases such as rheumatoid arthritis. This suggests a wider therapeutic role for CsA than is currently recognized. PMID- 2106910 TI - Effects of food on the central and peripheral haemodynamic response to upright exercise in normal volunteers. AB - The central and peripheral haemodynamic effects of a modest meal were investigated in healthy volunteers at rest and in response to submaximal exercise. The meal increased heart rate, cardiac output, oxygen consumption, carbon dioxide production, and minute ventilation at rest and during exercise. The effects of food were additive to those induced by the exercise. Food had no effect on limb blood flow and lowered total systemic vascular resistance suggesting that there were no compensatory changes in regional blood flow to help redirect blood to the gut. An increase in cardiac output, and therefore myocardial work, is the predominant cardiovascular response to eating and this may help explain the postprandial deterioration in symptoms of some patients with cardiovascular disorders. PMID- 2106911 TI - Immunocytochemical localisation of follicle stimulating hormone (FSH) in normal, benign and malignant human prostates. AB - Immunocytochemical localisation of follicle stimulating hormone (FSH) was carried out in normal, benign and malignant human prostates by indirect immunoperoxidase technique. Positive staining was observed in the epithelial cells of all the three categories, while the stromal cells showed a weakly positive reaction in a few specimens. The brown reaction product was dispersed in the cytoplasm of the epithelial cells. These observations demonstrate the presence of immunoreactive FSH-like peptide in human prostate. The significance of FSH in the aetiopathology of prostatic disorders is discussed. PMID- 2106912 TI - Relevance of class, molecular weight and isoelectric point in predicting human light chain amyloidogenicity. AB - The ability to predict the amyloidogenicity of certain light chains may facilitate an earlier diagnosis of AL amyloidosis and, possibly, lead to more effective treatment. Using current methods, available in clinical chemistry laboratories, we assessed the class, the relative molecular mass (Mr) and the isoelectric point of urinary monoclonal light chains from 35 patients with AL amyloidosis (A+) and 51 without amyloidosis (A-). The light chain class (LCC) was lambda in 77% and 45% of A+ and A- patients, respectively. Light chain fragments (LCF) with low Mr (12-18 x 10(3) were detected in the urine of 30/35 A+ patients and in 15/51 A- ones. The mean (SD) isoelectric point (pI) of A+ light chains was 4.8 (1.1) while in A- patients it was 6.2 (1.6). Univariate analysis showed significant differences between the two groups for the three parameters. Discriminant analysis gave a function which allowed a correct allocation of 81% of the cases between the two groups. PMID- 2106913 TI - Primary structure of a 7Fe ferredoxin from Streptomyces griseus. AB - The complete primary structure of a Streptomyces griseus (ATCC 13273) 7Fe ferredoxin, which can couple electron transfer between spinach ferredoxin reductase and S. griseus cytochrome P-450soy for NADPH-dependent substrate oxidation, has been determined by Edman degradation of the whole protein and peptides derived by Staphylococcus aureus V8 proteinase and trypsin digestion. The protein consists of 105 amino acids and has a calculated molecular weight, including seven irons and eight sulfurs, of 12,291. The ferredoxin sequence is highly homologous (73%) to that of the 7Fe ferredoxin from Mycobacterium smegmatis. The N-terminal half of the sequence, which is the Fe-S clusters binding domain, has more than 50% homology with other 7Fe ferredoxins. In particular, the seven cysteines known from the crystal structure of Azotobacter vinelandii ferredoxin I to be involved in binding the two Fe-S clusters are conserved. PMID- 2106914 TI - Cooperative effect of fructose bisphosphate and glyceraldehyde-3-phosphate dehydrogenase on aldolase action. AB - The combination of binding and kinetic approaches is suggested to study (i) the mechanism of substrate-modulated dynamic enzyme associations; (ii) the specificity of enzyme interactions. The effect of complex formation between aldolase and glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3 phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) on aldolase catalysis was investigated under pseudo-first-order conditions. No change in kcat but a significant increase in KM of fructose 1,6-bisphosphate for aldolase was found when both enzymes were obtained from muscle. In contrast, kcat rather than KM changed if dehydrogenase was isolated from yeast. Next, the conversion of fructose 1-phosphate was not affected by interactions between enzyme couples isolated from muscle. The influence of fructose phosphates on the enzyme-complex formation was studied by means of covalently attached fluorescent probe. We found that the interaction ws not perturbed by the presence of fructose 1-phosphate; however, fructose 1,6-bisphosphate altered the dissociation constant of the enzyme complex. A molecular model for fructose 1,6-bisphosphate-modulated enzyme interaction has been evaluated which suggests that high levels of fructose bisphosphate would drive the formation of the 'channelling' complex between aldolase and glyceraldehyde-3-phosphate dehydrogenase. PMID- 2106915 TI - Rapid kinetics of an N-terminal mutant of cyanobacterial ribulose-1,5 bisphosphate carboxylase/oxygenase. AB - The transient changes in absorption of visible light upon addition of ribulose 1,5-bisphosphate to Co2(+)-activated ribulose-1,5-bisphosphate carboxylase/oxygenase were used to show altered catalytic properties of a mutant form of the enzyme from Anacystis nidulans. The mutant form of the enzyme had a modified N-terminus and a 10-fold greater Km for ribulose 1,5-bisphosphate than the natural cyanobacterial enzyme. PMID- 2106916 TI - Elongation factor EF-1 alpha from Artemia is specifically labeled at Lys-63 by the guanine nucleotide analog pyridoxal-5'-diphospho-5'-guanosine. AB - We have synthesized the guanine nucleotide analog pyridoxal-5'-diphospho-5' guanosine. This compound specifically modifies a single lysine residue in elongation factor 1 alpha from Artemia, indicating that this residue is in close contact with the reactive part of the guanine nucleotide analog. This result is discussed in terms of the structure of the nucleotide-binding domain of the factor. PMID- 2106917 TI - Apolipoprotein AIMilano. Partial lecithin:cholesterol acyltransferase deficiency due to low levels of a functional enzyme. AB - The cholesterol esterification process was analyzed in 19 carriers of the apolipoprotein AIMilano (AIM) variant and in 19 age-sex matched controls by measuring lecithin:cholesterol acyltransferase (LCAT) mass, activity (i.e., cholesterol esterification with a standard proteoliposome substrate) and cholesterol esterification rate (i.e., cholesterol esterification in the presence of the endogenous substrate). The AIM subjects had lower LCAT mass (3.30 +/- 0.85 micrograms/ml), activity (71.1 +/- 36.4 nmol/ml per h) and cholesterol esterification rate (23.6 +/- 12.5 nmol/ml per h) compared to controls (5.22 +/- 0.74 micrograms/ml, 121.6 +/- 54.6 nmol/ml per h and 53.6 +/- 29.9 nmol/ml per h, respectively). The specific LCAT activity, i.e., LCAT activity per microgram of LCAT, was similar in the two groups, indicating that the LCAT protein in the AIM carriers is structurally and functionally normal. However, the specific cholesterol esterification rate was 23% lower in the AIM subjects (8.03 +/- 6.01 nmol/h per microgram) compared to controls (10.49 +/- 5.86 nmol/h per microgram; P less than 0.05). The capacity of HDL3, purified from both AIM and control plasma, to act as substrates for cholesterol esterification was similar, thus suggesting that other mechanism(s) may be in play. Carriers with a relative abundance of abnormal, small HDL3b particles had the most altered cholesterol esterification pattern. Upon evaluating all AIM subjects, a complex relationship between HDL structure, plasma lipid-lipoprotein levels and cholesterol esterification emerged, making the AIMilano condition a unique model for the study of the mechanisms regulating the cholesterol esterification-transfer process in man. PMID- 2106919 TI - Apo A-I metabolism in cynomolgus monkeys: male-female differences. AB - Female cynomolgus monkeys have significantly higher plasma apo A-I concentrations than males (P = 0.04) and are able to maintain higher levels than the males even after consuming a high-cholesterol diet that severely depresses the apo A-I concentration in primates (P less than 0.05). The mechanism responsible for this difference was investigated by comparing apo A-I turnover (synthesis and catabolism) in males and females consuming monkey chow and in a separate group of males and females that had consumed the high-cholesterol diet for several weeks. The average length of time an apo A-I molecule remained in the plasma compartment of chow-fed monkeys was 2.62 days but decreased to 1.52 days (P less than 0.01) in animals fed the HC diet. There were no male-female differences in the residence times. The absolute turnover rate (mg/day) of apo A-I was not statistically affected by diet or sex; however, the females were substantially smaller than the males (3.8 vs. 4.8 kg; P less than 0.01) and their plasma volumes were significantly smaller than those of the males, even after correction for differences in body wt. (32.6 vs. 37.0 ml/kg, respectively; P less than 0.01). Taken together, the data indicate that females cynomolgus monkeys have higher apo A-I synthesis rates than males of comparable plasma volume (P = 0.03), which we would propose accounts for the higher plasma apo A-I concentrations evident in females. PMID- 2106918 TI - Role of lipoxygenase in the mechanism of acrosome reaction in mammalian spermatozoa. AB - The acrosome reaction (AR) in bull spermatozoa was induced by the Ca2(+) ionophore A23187, by dilauroylphosphatidylcholine or by arachidonic acid in the presence of Ca2+ in the incubation medium. The occurrence of AR was determined by following the release of acrosin from the cells. Nordihydroguaiaretic acid (NDGA), an inhibitor of both lipoxygenase and prostaglandin-synthetase, caused 35%, 43% and 69% inhibition of AR at concentrations of 1, 10 or 100 microM, respectively. Eicosatetraynoic acid (ETYA), an analogue of arachidonic acid, caused 17%, 61% and 77% inhibition of AR at concentrations of 20, 40 or 80 micrograms/ml, respectively. When AR was induced by arachidonic acid, ETYA, causes 36% and 58% inhibition at concentrations of 2 or 20 micrograms/ml, respectively. Under identical conditions, 100 microM indomethacin, a specific inhibitor of prostaglandin-synthetase, showed no inhibition but rather 35% stimulation at acrosin release rate. The fact that AR is inhibited by NDGA and not by indomethacin indicates that the lipoxygenase, rather than prostaglandin synthetase, is involved in the mechanism of AR. Since the inhibition by NDGA is seen in the presence of the Ca-ionophore, we suggest that lipoxygenase activity is not involved in enhancing calcium transport into the cell, but rather at other steps in AR mechanism. A thin-layer chromatography revealed the presence of 15 HETE, the classical product of 15-lipoxygenase activity, which was identified by HPLC. Under AR conditions, there is an elevation of lipoxygenase products and the addition of NDGA caused a reduction in their levels. The inhibition of acrosin release by NDGA can be eliminated by adding 15-HETE or 15-HPETE to the incubation medium. In conclusion, we suggest here for the first time, a physiological role for 15-lipoxygenase in the mechanism of AR in mammalian spermatozoa. PMID- 2106920 TI - Thermofusion of cells. AB - This communication provides evidence that the thermo-osmotically induced membrane defects and fluxes occurring in plant protoplasts may initiate internalization and fusion of adjacent cells. This phenomenon is called thermofusion of cells. PMID- 2106921 TI - Observations on the intestinal colonization by Pseudomonas aeruginosa in newborn infants. AB - We studied the intestinal flora of 23 newborns, whose meconium had yielded a pure culture of Pseudomonas aeruginosa on blood agar medium. Twelve infants had a single serotype of P. aeruginosa in their meconium, 10 had a second serotype and the last infant was carrying three distinct ones. The maximum levels of P. aeruginosa observed during the first week of life were variable among the infants: 1 x 10(3) to 1 x 10(10) CFU/g of stools. The levels diminished progressively afterwards, and after 1 year of age only 1 of the 13 infants examined remained a carrier of P. aeruginosa. In 11 infants a second or a third serotype occurred during the course of the study. The serotypes that appeared secondarily always disappeared before the initial ones. Antibiotics: ampicillin + gentamicin or cefotaxime + netilmicin and colistin which were given to 8 infants had no clear effect on P. aeruginosa levels. Four infants had delayed colonization by Escherichia coli of greater than or equal to 10 days. All 4 had high levels of P. aeruginosa: 1 x 10(7) to 1 x 10(10) CFU/g stool, and antibiotic therapy, rendering it impossible to assess which was the cause of this delay. This colonization by P. aeruginosa did not lead to any clinical trouble. PMID- 2106922 TI - Hypofrontality and cognitive impairment in schizophrenia: dynamic single-photon tomography and neuropsychological assessment of schizophrenic brain function. AB - Regional cerebral blood flow (rCBF) was assessed in 40 chronic male schizophrenic patients (20 medicated, 20 unmedicated) and 31 matched normal controls with Dynamic Single-photon Emission Computed Tomography (D-SPECT). Blind analyses of normalized color-coded tomograms revealed significant bifrontal and bitemporal rCBF deficits in the patient group. Frontal flow deficits were most prominent in paranoid patients (n = 21) and right temporal deficits were most prominent in nonparanoid patients (n = 19). These relative regional declines were observed within the context of significantly elevated hemispheric blood flow in schizophrenics compared with controls. Reduced left frontal rCBF was associated with neuropsychological impairment on the Wisconsin Card Sorting Test and Luria Nebraska Battery. Increased hemispheric CBF was correlated with the presence of positive schizophrenic symptoms. Medication status was unrelated to rCBF. These findings demonstrate that hypofrontality has important implications for cognitive function in some schizophrenic individuals. PMID- 2106923 TI - Immunization of rams against human recombinant inhibin alpha-subunit delays, augments, and extends season-related increase in blood gonadotropin levels. AB - Adult Suffolk rams were immunized four times against the human recombinant inhibin alpha-subunit over a period of 80 days. Blood samples were collected at weekly intervals and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were determined by radioimmunoassay procedures. The results show that season-related elevations of gonadotropin levels in immunized rams was delayed by 1-2 wk and, in these animals, it was more pronounced and extended than in vehicle-treated controls. Peaks of circulating testosterone were higher in control rams than in immunized animals. The capacity of the antisera to bind 125I-labeled inhibin alpha-subunit increased significantly in each immunized animal within 30 days of treatment, even though neutralizing antibodies were detected with a rat pituitary cell culture bioassay in only one of the four immunized rams. Epididymal sperm reserves tended to be greater in immunized than in control animals. These results show that inhibin controls the release of FSH during the breeding season, thereby regulating spermatogenic activity; it may also exert its effect on testicular function by a local effect on Leydig cells, as evidenced by changes in serum testosterone profiles and increased serum LH levels in rams immunized against the inhibin alpha-subunit. PMID- 2106924 TI - Food handlers and food poisoning. PMID- 2106925 TI - Emphysematous bullae. PMID- 2106926 TI - Intact parathyroid hormone assays. PMID- 2106927 TI - Pneumocystis carinii pneumonia. PMID- 2106928 TI - After the epidemic: follow up study of HIV seroprevalence and changing patterns of drug use. AB - OBJECTIVE: To follow up known intravenous drug users to determine current health state and drug use, compare characteristics with those of recent drug users, and examine HIV exposure and serostate. DESIGN: Subjects were identified from conventional general practice records and recruited from 1980 to the end of 1985; they were followed up during 1987 and 1988 and compared with drug users identified in the same way but recruited after 1985. SETTING: General practice and community in north west Edinburgh. Follow up conducted throughout the United Kingdom. SUBJECTS: Subjects known to have injected illegal drugs before 1986 (n = 203) and since that time. MAIN OUTCOME MEASURES: Mortality from and prevalence of HIV seropositivity and various parameters indicative of abstinence. RESULTS: Of the 203 subjects in the follow up group, 189 (93%) were traced; 16 (8%) had died and the remaining 173 (85%) were interviewed. In all, 146 (72% of the follow up cohort) had been tested for HIV antibodies, 94 (64%) having positive and 52 (36%) negative results; 57 (28%) had not been tested. Of the 65 subjects in the recently recruited group, 51 (79%) had been tested for HIV, 15 (29%) having positive results. A further 21 (43%) were currently negative for HIV antibody but still at risk. Thirty three (19%) of those followed up were confirmed abstinent, although more (about half) showed evidence of diminished drug injecting. Age correlated strongly with abstinence (p less than 0.001). One third of the group currently used cannabis, buprenorphine, dihydrocodeine, or diazepam. When the two groups were analysed together there was a strong association between the date of starting injecting and HIV seropositivity (chi 3 = 23.81, df = 2, p less than 0.001), with a peak around 1980-3. CONCLUSIONS: Although only a fifth of the followed up group were convincingly abstinent, a much larger group showed evidence of prolonged periods of remission. Overall, much use of oral drugs was confirmed and worrying trends towards taking buprenorphine and benzodiazepines were evident. The peak incidence of starting drug use and the comparatively low seroprevalence of HIV in the newer drug users probably explain the anomalous high seroprevalence in Edinburgh drug users during 1980-5. The epidemic of HIV during the first half of the 1980s in the group suggests that the virus was probably being transmitted because of a pattern of behaviour. Changing patterns of HIV transmission suggest a need to concentrate on heterosexual transmission as the main problem in the future. PMID- 2106929 TI - Making better decisions: construction of clinical scoring systems by the Spiegelhalter-Knill-Jones approach. AB - A study was carried out assessing the practical use of a simple system of scoring information which can help in making a diagnosis or establishing a prognosis in an individual patient. The system was introduced in 1984 for use in gastroenterology, but it can be employed in a wide range of medical and surgical settings. This series was concerned with predicting postoperative respiratory complications in a group of elderly surgical patients. The system combines elements from Baye's theorem and logistic regression, though no mathematical knowledge is required to apply it in clinical practice. The method by which results are presented is easy to understand, yet at the same time more complex ideas such as conflict of evidence and doubt may be embraced if the clinician so desires. PMID- 2106930 TI - Lichen planus and liver diseases: a multicentre case-control study. Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). AB - OBJECTIVE: To assess the association of lichen planus with liver complaints and with known aetiological factors of liver diseases. DESIGN: Multicentre case control study. Interviews were conducted by trained medical investigators on the basis of a structured questionnaire. At the interview patients and controls were asked for consent to blood samples being taken to determine transaminase activities and the presence of hepatitis B virus surface antigen. SETTING: Outpatient departments of 27 Italian general and teaching hospitals that were collaborating in the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). SUBJECTS: Incident cases and controls were eligible. A total of 577 patients with lichen planus and 1031 controls with dermatological diseases other than lichen planus were interviewed. Less than 1% of the people contacted refused to participate. Patients and controls were matched for sex and age in five year intervals. RESULTS: The risk of lichen planus was higher in patients with a history of liver diseases requiring hospital admission or specialist consultation (relative risk = 1.6; 95% confidence interval = 1.2 to 2.2), those who had had liver biopsy (5.5; 1.9 to 15.6), and those with a history of viral hepatitis (1.9; 1.1 to 3.1). High activities of liver enzymes and positive results of tests for hepatitis B virus surface antigen were also associated with lichen planus. The association with alcohol consumption was not clearly confirmed by a dose-risk relation. CONCLUSION: This study adds quantitative epidemiological evidence to the clinical observation that liver disease is a risk factor for lichen planus although not a specific marker of it. PMID- 2106931 TI - Analysis of serial measurements in medical research. AB - In medical research data are often collected serially on subjects. The statistical analysis of such data is often inadequate in two ways: it may fail to settle clinically relevant questions and it may be statistically invalid. A commonly used method which compares groups at a series of time points, possibly with t tests, is flawed on both counts. There may, however, be a remedy, which takes the form of a two stage method that uses summary measures. In the first stage a suitable summary of the response in an individual, such as a rate of change or an area under a curve, is identified and calculated for each subject. In the second stage these summary measures are analysed by simple statistical techniques as though they were raw data. The method is statistically valid and likely to be more relevant to the study questions. If this method is borne in mind when the experiment is being planned it should promote studies with enough subjects and sufficient observations at critical times to enable useful conclusions to be drawn. Use of summary measures to analyse serial measurements, though not new, is potentially a useful and simple tool in medical research. PMID- 2106932 TI - Favism in the African type of glucose-6-phosphate dehydrogenase deficiency (A-). PMID- 2106933 TI - Postneonatal mortality among illegitimate children registered by one or both parents. PMID- 2106934 TI - Districts' use of thrombolytic agents. PMID- 2106935 TI - Relation between cognitive impairment and early death in the elderly. AB - STUDY OBJECTIVE: To study the association between cognitive impairment and early death in elderly patients living in the community. DESIGN: Case-control study of 410 patients assessed by the mental status questionnaire and followed up after three years. SETTING: A general practice in Inverurie, Aberdeenshire, with 14,000 patients. PATIENTS: 205 Patients aged greater than or equal to 65 with cognitive impairment according to the mental status questionnaire (score less than or equal to 8) and 205 patients scoring greater than 8 on the questionnaire matched for age and sex. MAIN OUTCOME MEASURE: Death. RESULTS: The relative risk of death in the cognitively impaired patients overall was 3.5. Those patients who scored less than or equal to 7 on the mental status questionnaire were five times more likely to die than their controls. There was no difference in risk of death between those with severe or moderate cognitive impairment. CONCLUSIONS: Cognitive impairment is associated with early death. PMID- 2106936 TI - Facilitating care of patients with HIV infection by hospital and primary care teams. AB - To complement the role of primary care teams working with patients with HIV disease and AIDS within greater London and to ease the load on the special hospital units a home support team was developed. It comprises six specialist nurses, a general practitioner trained medical officer, and a receptionist and is funded from regional and district sources and charities. A nurse is available for out of hours and emergency weekend calls, with support from the patient's general practitioner or the attached medical officer. During the first 18 months 249 patients were seen; the mean duration of care was five months. Nearly a third (18/50, 30%) of patients who were terminally ill died at home. The team's activities included practical nursing care, emotional support for carers and patients, and advice and guidance to primary care teams. Problems in providing care in patients' homes included issues relating to confidentiality and 24 hour cover. With the increasing incidence of HIV infection the home support team may be a useful model for care of large numbers of patients with symptomatic HIV disease, especially in large urban areas. PMID- 2106937 TI - AIDS, housing, and health. PMID- 2106938 TI - Housing and health: Families and flats. PMID- 2106940 TI - Unifying biology. PMID- 2106939 TI - ABC of transfusion. Transfusion of red cells. PMID- 2106941 TI - Overprescription of cholera vaccine. PMID- 2106942 TI - Cardiopulmonary resuscitation and the MRCGP examination. PMID- 2106943 TI - Radiography in women of childbearing ability. PMID- 2106944 TI - Child health surveillance. PMID- 2106945 TI - Osteoarthritis. PMID- 2106946 TI - Calcium channel blockers in myocardial infarction. PMID- 2106947 TI - Psychiatric discharge summaries. PMID- 2106948 TI - Anaesthesia and Colles' fractures. PMID- 2106949 TI - Cancer of the oesophagus. PMID- 2106950 TI - Oxytocin infusion in primiparous women using epidural analgesia. PMID- 2106951 TI - Hearing problems of elderly people. PMID- 2106952 TI - Arctic willy. PMID- 2106953 TI - Treatment with co-trimoxazole for urinary tract infections in women. PMID- 2106954 TI - Interleukin 2. PMID- 2106955 TI - Vigabatrin. PMID- 2106956 TI - Non-steroidal anti-inflammatory drugs and peptic ulcers. PMID- 2106957 TI - Migration and geographic variations in blood pressure in Britain. AB - OBJECTIVE: To evaluate the relative contributions of factors acting at different stages in life to regional differences in adult blood pressure. DESIGN: Prospective cohort study (British regional heart study). SETTING: One general practice in each of 24 towns in Britain. SUBJECTS: 7735 Men aged 40-59 years when screened in 1978-80 whose geographic zone of birth and zone of examination were classified as south of England, midlands and Wales, north of England, and Scotland. Non-migrants (n = 3144) were born in the town where they were examined; internal migrants (n = 4147) were born in Great Britain but not in the town where they were examined; and international migrants (n = 422) were born outside Great Britain. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures and height. RESULTS: Regardless of where they were born, men living in the south of England had lower mean blood pressures than men living in Scotland (142.5/80.1 v 148.1/85.2 mm Hg). The effects of the place of birth and place of examination on adult blood pressure were examined in a multiple regression model. For internal migrants the modelled increase in mean systolic blood pressure across adjacent zones of examination was 2.1 mm Hg (95% confidence interval 1.3 to 2.9); for adjacent zones of birth the corresponding increase was 0.1 mm Hg (-0.7 to 0.7). The place of examination seemed to be a far more important determinant of mean adult blood pressure than the place of birth. Height is an accepted marker of genetic and early life influences. Regional differences in height were therefore analysed to test whether the multiple regression model could correctly distinguish between the influence of place of birth and place of examination. As expected, men born in Scotland were shorter on average than men born in the south of England irrespective of where they lived in Britain (172.6 cm v 175.1 cm for internal migrants). CONCLUSION: Regional variations in blood pressure were strongly influenced by where the men had lived for most of their adult lives rather than by where they were born and brought up. Among middle aged men, factors acting in adult life seemed to be more important determinants of regional differences in blood pressure than those acting early in life such as genetic inheritance, intrauterine environment, and childhood experience. PMID- 2106958 TI - Examination of fetuses after induced abortion for fetal abnormality. AB - OBJECTIVE: To determine the accuracy of midtrimester diagnosis of fetal abnormality by examination and investigation of fetuses after induced abortion. DESIGN: Prospective study over five years of fetuses aborted in the midtrimester because of abnormalities detected by ultrasonography and amniocentesis. Techniques included a full external examination by a clinical geneticist with experience in dysmorphology and other investigations including necropsy. SETTING: Regional genetic centre. PARTICIPANTS: Clinicians working within the North Western region who wished to use the service offered. RESULTS: 133 Fetuses were aborted because of abnormalities detected on ultrasonography and 115 because of abnormal findings on amniotic fluid analysis. In a further two cases fetal abnormality was diagnosed by molecular genetic and biochemical techniques. Among the fetuses with abnormal scans the pretermination diagnosis was changed or refined in a way which affected genetic counselling in 53 of 133 cases. Among the 115 fetuses diagnosed as abnormal by amniocentesis the pretermination diagnosis was confirmed in 112 cases and altered in three. CONCLUSION: Fetuses aborted because of abnormalities detected by screening should be examined by suitably experienced clinicians, both for accurate genetic counselling of the families and for quality control of the tests employed. PMID- 2106959 TI - Microalbuminuria as predictor of increased mortality in elderly people. AB - OBJECTIVE: Correlation of the urinary albumin excretion rate and the risk of death among elderly subjects. DESIGN: 216 Subjects aged 60-74 whose urinary albumin excretion rate had been determined were followed up 62-83 months later. SETTING: Municipality of Fredericia, Denmark. SUBJECTS: 223 People who had been selected as control subjects for diabetics found during a systematic screening for diabetes of all people aged 60-74 living in the municipality of Fredericia, Denmark. Of these subjects, 216 had an extensive clinical and biochemical examination within a few weeks of selection. MAIN OUTCOME MEASURE: Death. RESULTS: The median urinary albumin excretion rate was 7.52 micrograms/min. Eight of those with a rate below the median died compared with 23 with a rate equal to or greater than the median (p = 0.0078). The median albumin excretion rate in the 31 who died was 15.00 micrograms/min. Cardiovascular disease was the most common cause of death in both groups. A multivariate regression analysis of survival data was performed using the proportional hazards model. Besides albumin excretion rate, male sex, serum creatinine concentration, and hypertension were found to be of prognostic value. CONCLUSIONS: The association between the albumin excretion rate and mortality that has been described in recent years in patients with diabetes mellitus may be present in elderly people in general, even when other known risk factors are taken into account. PMID- 2106960 TI - Screening for prolonged incubation of HTLV-I infection in British and Jamaican relatives of British patients with tropical spastic paraparesis. AB - OBJECTIVE: To compare the prevalence of antibody to and proviral DNA of the retrovirus HTLV-I in relatives of 11 British patients with tropical spastic paraparesis who had migrated from Jamaica before they developed symptoms, and to examine factors possibly related to transmission of HTLV-I. DESIGN: Migrant, family study. Antibody state was determined by several methods and confirmed by western blotting; the polymerase chain reaction was used to detect proviral DNA. SETTING: Britain and Jamaica. SUBJECTS: All available first degree relatives: those born and still resident in Jamaica (group 1); those born in Jamaica who migrated to Britain (group 2); and index patients' children who were born and resident in Britain (group 3). All had been breast fed and none had had blood transfusions. RESULTS: Of the 66 living relatives, 60 were traced. Seroprevalence among those born in Jamaica (irrespective of current residence) was 22% (10/46; 95% confidence limits 9 to 34%) compared with zero among British born offspring (0/14) and was higher in group 2 at 33% (7/21; 12 to 55%) than in group 1 at 12% (3/25; 0 to 25%). (Patients in group 1 had the greatest mean age.) Proviral DNA was not detected in any subject negative for HTLV-I antibody, making prolonged viral incubation in those negative for the antibody unlikely. CONCLUSION: In this sample factors related to place of birth and early residence were more important in transmission of HTLV-I than maternal or age effects. In areas with a low to moderate prevalence policies of preventing mothers who are carriers of the virus from breast feeding would be premature. PMID- 2106961 TI - Absorption of glycine irrigating solution during transcervical resection of endometrium. PMID- 2106962 TI - Should radiologists talk to patients? PMID- 2106963 TI - Promotion by the British pharmaceutical industry, 1983-8: a critical analysis of self regulation. AB - Since 1958 the Association of the British Pharmaceutical Industry (ABPI) has attempted to regulate the promotion of prescription medicines through its code of practice. This regulation is described and analysed for the six years 1983-8 using the reports on 302 complaints considered by its code of practice committee and annual reports. The complaints came mainly from doctors (143, 48%) and competing companies (103, 33%). The committee found a total of 379 breaches of the code in 192 (63%) of the complaints. Additional breaches were detected by informational scrutiny of advertisements by the ABPI secretariat. Analysis showed that 270 (71%) of these breaches involved possible breaches of the Medicines Act. The rules that forbid misleading or unsubstantiated information and misleading claims or comparisons were broken most often. The committee found the most frequent offenders to be Organon (32 breaches), Smith Kline and French (23), Glaxo (21), A H Robins (18), Bayer (17), Merck Sharp and Dohme (17), and Lederle (16). Often the promotion of one product led to several breaches. The promotional wars over histamine H2 receptor antagonists accounted for 33 breaches. It is estimated that in 1983-8 about 100 breaches of the code were detected a year. In the 18 years 1972-88 the Medicines Act was breached probably over 1200 times. Health ministers, by not enforcing the regulations controlling promotion, have abrogated their responsibility to the ABPI, but the evidence suggests that the code has failed to deter promotional excesses. The ABPI's wish to secure compliance with the code seems weaker than its wish to pre-empt outside criticism and action: its self regulation seems to be a service to itself rather than to the public. It is suggested that the code of practice committee should become publicly accountable, that the majority of its members should represent the health professions and the public, and that effective sanctions are needed. PMID- 2106964 TI - Fertile flukes and mediating molluscs. PMID- 2106965 TI - Life threatening thrombocytopenia in sarcoidosis. PMID- 2106966 TI - Late complication of undetected odontoid fracture in children. PMID- 2106967 TI - Superglue inadvertently used as eyedrops. PMID- 2106968 TI - Alteration in diabetic control after a change in insulin manufacture. PMID- 2106969 TI - Early exercise testing after myocardial infarction. PMID- 2106970 TI - Ovarian failure after total body irradiation. PMID- 2106971 TI - Reduction of stress in carers of patients with dementia. PMID- 2106972 TI - Transabdominal ultrasound screening for early ovarian cancer. PMID- 2106973 TI - Transvaginal colour flow imaging and ovarian cancer. PMID- 2106974 TI - Mortality among oral contraceptive users. PMID- 2106975 TI - Renal replacement treatment in patients with spina bifida or spinal cord injury. PMID- 2106976 TI - Computer control of anticoagulant dose. PMID- 2106977 TI - Breast screening. PMID- 2106978 TI - Paget's disease in a painting by Quinten Metsys (Massys) PMID- 2106979 TI - Doctors and medical negligence. PMID- 2106980 TI - Stopping steroids in polymyalgia rheumatica and giant cell arteritis. PMID- 2106981 TI - Identification of the cystic fibrosis gene. PMID- 2106982 TI - Node negative breast cancer. PMID- 2106983 TI - Management of acute coronary occlusion during percutaneous transluminal coronary angioplasty: experience of complications in a hospital without on site facilities for cardiac surgery. AB - OBJECTIVE: To determine whether percutaneous transluminal coronary angioplasty may be safely performed in cardiology centres in the United Kingdom without immediate on site cardiac surgical cover for complications arising at angioplasty. DESIGN: Retrospective review of coronary angioplasties and complications in a hospital without on site cardiac surgical cover. SETTING: All angioplasties were performed in the catheterisation laboratory of the Belfast City Hospital. Revascularisation surgery for complicated coronary angioplasty was performed in the cardiac surgical unit of the Royal Victoria Hospital, 2.4 km away from the catheterisation laboratory. PATIENTS: 540 Coronary angioplasties were performed on 512 patients between late 1982 and November 1988. Indications included stable angina, unstable rest angina, and suitable coronary disease at coronary arteriography after myocardial infarction. MAIN OUTCOME MEASURES: In hospital mortality after complicated coronary angioplasty and delay to surgical revascularisation after acute coronary occlusion at angioplasty. RESULTS: Coronary angioplasty was successful in 444 cases (82%). Acute coronary occlusion occurred in 35 cases (6.5%). Twelve patients required urgent revascularisation surgery and were transferred safely to the surgical unit; none of these patients died. A mean delay of 268 minutes (range 180-390 minutes) occurred before revascularisation compared with 273 minutes (range 108-420 minutes) in the Royal Victoria Hospital, where on site surgical cover was available. The principal cause of delay was the wait for a cardiac operating theatre to become available and not the transfer time between hospitals. Five deaths occurred after coronary angioplasty, a mortality of 0.9%. Three deaths were related to acute coronary occlusion. The absence of immediate surgical help did not influence the outcome in any patient. CONCLUSION: With careful selection of patients coronary angioplasty may be safely performed in a hospital without on site cardiac surgical facilities, provided that these are available at a nearby centre. PMID- 2106984 TI - Non-invasive mechanical ventilation for acute respiratory failure. AB - The value of mechanical ventilation using intermittent positive pressure ventilation delivered non-invasively by nasal mask was assessed in six patients with life threatening exacerbations of chronic respiratory disease. Median (range) arterial oxygen and carbon dioxide tensions were 4.4 (3.5-7.2) kPa and 8.7 (5.5-10.9) kPa respectively, with four patients breathing air and two controlled concentrations of oxygen. The arterial oxygen tension increased with mechanical ventilation to a median (range) of 8.7 (8.0-12.6) kPa and the carbon dioxide tension fell to 8.2 (6.5-9.2) kPa. Four patients discharged after a median of 10 (8-17) days in hospital were well five to 22 months later. One died at four days of worsening sputum retention and another after five weeks using the ventilator for 12-16 hours each day while awaiting heart-lung transplantation. This technique of mechanical ventilation avoids endotracheal intubation and can be used intermittently. Hypercapnic respiratory failure can be relieved in patients with either restrictive or obstructive lung disease in whom controlled oxygen treatment results in unacceptable hypercapnia. Respiratory assistance can be tailored to individual need and undertaken without conventional intensive care facilities. PMID- 2106985 TI - Sleepwalking, night terrors, and consciousness. AB - OBJECTIVE: To determine some personality and psychoneurotic characteristics of adults who have the sleepwalking-night terrors syndrome. DESIGN: Prospective assessment of two groups of consecutive patients with a firm diagnosis of either of two specific sleep disorders as established clinically and by polysomnography. SETTING: Outpatient sleep disorders clinic and sleep laboratory in a tertiary referral centre. PATIENTS: 12 Patients referred consecutively to the clinic in whom a diagnosis of sleepwalking (six) or night terrors (six) was confirmed. MAIN OUTCOME MEASURES: Psychological characteristics as measured at the time of clinical assessment by means of the Eysenck personality questionnaire, the hostility and direction of hostility questionnaire, and the Crown-Crisp experiential index. RESULTS: Both groups scored exceptionally highly on the hysteria scale of the Crown-Crisp experiential index and the night terrors group also scored highly on the anxiety scale. The patients with sleepwalking also scored highly on a measure of externally directed hostility. CONCLUSIONS: The physiological and psychological features identified in these patients, possibly reflecting different expressions of a constitutional cerebral characteristic, may be explored in terms of hysterical dissociation. The findings contribute to the debate concerning the nature of sleepwalking, in particular with and without the forensic aspects. PMID- 2106986 TI - Risks of acute traumatic intracranial haematoma in children and adults: implications for managing head injuries. AB - OBJECTIVE: To determine the factors influencing the risk of an acute traumatic intracranial haematoma in children and adults with a recent head injury. DESIGN: Prospective study of incidence of risk factors in samples of patients attending accident and emergency departments and in all patients having an acute traumatic intracranial haematoma evacuated in one regional neurosurgical unit during 11 years. SETTING: Accident and emergency departments in Scotland or Teesside and regional neurosurgical centre in Glasgow. PATIENTS: 8406 Adults and children (less than or equal to 14 years) who attended accident and emergency departments and 1007 consecutive patients who had an operation for an acute traumatic intracranial haematoma. Data were complete in 8366 and 960 patients respectively. RESULTS: Overall, children were less at risk than adults (one in 2100 v one in 348 respectively). In both age groups the presence of a skull fracture and changes in conscious level permitted identification of subgroups of patients with widely differing degrees of risk. In children the absolute risk ranged from one in almost 13,000 without a fracture or altered conscious level to one in 12 for a child in a coma and with a fracture; the pattern was similar in adults, the risks in corresponding groups ranging from one in almost 7900 to one in four. CONCLUSIONS: Although children attending hospital after a head injury have a lower overall risk of a traumatic haematoma, the main indicators of risk, a skull fracture and conscious level, are the same as in adults, and the pattern of their combined effect is similar. Guidelines for managing adults with recent head injury may therefore be applied safely to children; with the increasing provision of facilities for computed tomography they should be revised to ensure early scanning of more patients with head injury. PMID- 2106987 TI - Comparison of visual and radiographic detection of bony changes at the knee joint. PMID- 2106988 TI - Effect of non-steroidal anti-inflammatory drugs on dyspeptic symptoms. PMID- 2106989 TI - Restoration of perception of hypoglycaemia after hemiparesis in an insulin dependent diabetic patient. PMID- 2106990 TI - Does vasectomy accelerate testicular tumour? Importance of testicular examinations before and after vasectomy. PMID- 2106991 TI - Assessment of care of children with sickle cell disease: implications for neonatal screening programmes. AB - OBJECTIVE: To assess the quality of care provided by hospitals for young children with sickle cell disease. DESIGN: Retrospective survey. SETTING: Teaching hospital in London. PATIENTS: 31 Children (mean age 4 years 4 months, range 4 months to 7 years 5 months) born with sickle cell disease between 1978 and 1985 identified from Hospital Activity Analysis data, an outpatient diagnostic register, and registers of the haematology department. Eight had been diagnosed on neonatal screening and at least four of these had not been followed up. MAIN OUTCOME MEASURES: Aspects of quality of outpatient care (blood testing, clinic attendance, and prophylactic drug treatment) and family care (adequate support and carers' knowledge about the disease) as assessed by reviewing the notes and administering a semistructured questionnaire to the carers, in relation to a devised list of standards deemed necessary to ensure achievement of the aims of screening. RESULTS: There were 93 outpatient attendances during the previous 12 months, but 13 children had not attended at least every six months and four not at all for more than a year. Only eight children had had three of the blood tests considered to be necessary for good care; three had had none. Prophylactic treatment with penicillin and folic acid was erratic; three children with sickle cell anaemia were not receiving regular prophylactic penicillin. IMPLICATION: Diagnosis of sickle cell disease on neonatal screening must be linked with follow up to ensure optimal management. PMID- 2106992 TI - Open access gastroscopy: too much to swallow? AB - OBJECTIVES: To ascertain the proportion of endoscopic examinations with normal findings in patients referred for gastroscopy through hospital medical staff or directly by their general practitioner and to assess the likely effect of targeting endoscopy in older patients. DESIGN: Retrospective audit of the gastroscopy practice of one consultant from 1986 to 1988 from information recorded on a standard form completed at the time of the examination, which contained details of patients, their endoscopic findings, and mode of referral (open access or clinic). SETTING: One district general hospital. PATIENTS: 1545 Consecutive patients from primary catchment area attending for their first gastroscopy; 454 were referred through the outpatient clinic or by hospital colleagues (clinic group) and 1091 were accepted for endoscopy solely on their general practitioner's clinical diagnosis (open access group). RESULTS: Similar numbers (about 40%) of examinations with normal findings were performed in each group, although in patients aged over 40 the proportion with normal findings was significantly higher in the clinic group (p less than 0.03). Endoscopic evidence of gastro-oesophageal reflux disease, peptic ulceration, and gastroduodenal inflammation was equally common in each group; upper gastrointestinal malignancy, however, was significantly more common in patients referred through hospital doctors (5%, 23/454 v 2%, 22/1091 respectively; p less than 0.005) (although many of these patients had already been extensively investigated). IMPLICATIONS: Open access gastroscopy does not increase the number of unnecessary examinations and should become more widely available. Targeting this service to patients aged over 40 would reduce the number of requests but increase the diagnostic yield. PMID- 2106993 TI - Cervical cytology in the Vale of Trent faculty of the Royal College of General Practitioners, 1985-8. AB - OBJECTIVE: To assess changes in the organisation and performance of cervical cytology programmes in the practices of members of the Vale of Trent faculty of the Royal College of General Practitioners. DESIGN: Retrospective audits completed in 1985 and 1988 by general practitioners on a sequential sample of 100 records of women aged 35-64 in their practice. SETTING: General practices in which one or more partners were members or associates of the Vale of Trent faculty of the college, of which 76 participated in the first audit and 55 (82% of 67 eligible practices) in the second. SUBJECTS: Sequential samples of 100 women born between 1 January 1920 and 31 December 1949 (first audit) and between 1 January 1923 and 31 December 1952 (second audit) whose surnames began with P or B respectively. MAIN OUTCOME MEASURES: Percentage of women in each practice with a record of cervical cytology performed in the previous five years and percentage with no recorded smear. RESULTS: Of the 76 practices completing the audit in 1985, 55 (82% of those eligible) repeated the exercise in 1988. Performance was not significantly different in practices that did and did not respond. The median percentage of women who had had a smear in the previous five years was 49% and 69% in 1985 and 1988 respectively (p less than 0.001) and that of women with no record of a cervical smear was 28% and 16% respectively (p less than 0.001). All but six practices showed improvement in both outcome measures. In both audits an active call system was associated with a significantly increased performance (p less than 0.05). In nine practices (16%) 80% or more of the samples of women had had a smear in the previous five years. CONCLUSION: Organisation and performance of practices audited improved between 1985 and 1988. Although this might result from participation in the first audit, it probably represents a more general trend within primary care. ACTION: Between the two audits more practices (87% v 67%) had developed a policy on screening, and this was more likely to include the aim of performing regular smears on all sexually active women (98% v 80%). PMID- 2106994 TI - Audit in person: Problem solving with audit in general practice. PMID- 2106995 TI - Audit in person: Defining essential hospital data. PMID- 2106996 TI - Crisis in our hospital kitchens: ancillary staffing levels during an outbreak of food poisoning in a long stay hospital. AB - An investigation into an outbreak of food poisoning caused by Clostridium perfringens showed evidence of poor food handling by catering staff. The reasons behind this were explored by interviewing catering staff, analysing shifts and rotas, and looking at staff vacancies. Morale was low because of staff shortages resulting from a long term recruitment problem. In consequence staff were working double shifts and often for weeks on end without a day off. The reasons for the recruitment problem included the difficulty of recruiting semiskilled labour from a middle class area, low wages, lack of management support, and the poor image of the hospital as a place of work. Similar factors affect the recruitment and retention of ancillary staff nationally. The NHS has a poor record as an employer of ancillary staff, paying lower wages than other organisations for equivalent posts. Competitive tendering has further worsened the position of ancillary staff, with the result that good quality of care and service has often not been achieved. The NHS Review, with its emphasis on quality of care, makes no mention of ancillary staff. Yet high standards of ancillary provision are essential if further outbreaks of food poisoning in hospitals are to be prevented. PMID- 2106997 TI - ABC of transfusion. Infectious complications of blood transfusion: bacteria and parasites. PMID- 2106998 TI - Housing and health: Getting things done. PMID- 2106999 TI - Research ethics committees. PMID- 2107000 TI - Hypernatraemic dehydration in patients in a large hospital for the mentally handicapped. PMID- 2107001 TI - Avoidable factors contributing to death of children with head injury. PMID- 2107002 TI - Quality of life after surgery for benign oesophageal stricture. PMID- 2107003 TI - Scottish hearts but British habits. PMID- 2107004 TI - Anticardiolipin antibody. PMID- 2107005 TI - Oxytocin infusion during second stage of labour with epidural analgesia. PMID- 2107006 TI - Rat bites and leprosy. PMID- 2107007 TI - Bone marrow transplantation for advanced acute leukemia: a pilot study of high energy total body irradiation, cyclophosphamide and continuous infusion etoposide. AB - Leukemic relapse following bone marrow transplantation (BMT) for acute leukemia is the most common cause of treatment failure. Because a more intensive pre transplant preparative regimen may prevent disease recurrence we have designed a novel intensive conditioning regimen for BMT using high-energy total body irradiation (total dose 850 cGy; energy 24 MV; midplane received dose rate 26 cGy/min; day -6) followed by cyclophosphamide (dose 50 mg/kg/day; schedule 2-h infusion; days -5, -4, -3) and continuous infusion high-dose etoposide (dose 500 mg/m2/day; schedule: 22-h infusion; days -5, -4, -3). Between February 1987 and December 1988, 45 patients with advanced acute leukemia received transplants using this regimen. Twenty-five purged auto-transplants were done for B-lineage (n = 18), T-lineage (n = 6) or biphenotypic (n = 1) acute lymphoblastic leukemia, with 12 in remission and 13 in relapse at the time of transplantation. Of these, nine had non-relapse deaths and 16 have relapsed between 1 and 19 months (median 3 months) following transplantation. Of note all the T-lineage patients relapsed including two transplanted in remission and five transplanted in relapse. Nineteen patients received histocompatible allogeneic transplants and one underwent syngeneic transplantation. Of seven patients with acute lymphoblastic leukemia transplanted in refractory relapse, three have had an overt relapse, three died of interstitial pneumonitis and only one survives disease free 15 months after transplantation. Of 13 patients with acute non-lymphocytic leukemia and variants (11 who were transplanted in relapse) three died without relapse, three have relapsed and seven survive disease free from 9 to 27 months (median 20 months) after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107008 TI - The effect of carbon dioxide laser on wound contraction and epithelial regeneration in rabbits. AB - This study was undertaken to compare objectively healing rates (in rabbits) of wounds caused by CO2 laser with those caused by scalpel. The rates of contraction and epithelialisation of standard wounds were determined with daily measurement of wound area from the time of wounding until the wound had healed. Our results demonstrate significant delays in both wound contraction (p = 0.0001) and epithelialisation (p = 0.0001) for CO2 laser-created wounds when compared to those seen in scalpel-created wounds. Normal epithelial regenerative capacities were demonstrated in the laser group despite the slow onset of epithelial migration. The appearance of the healed areas appeared comparable for both modalities. PMID- 2107009 TI - Clinical evaluation of a new bilayer "artificial skin" composed of collagen sponge and silicone layer. AB - A bilayer "artificial skin" composed of an outer layer of silicone and an inner sponge layer of collagen and chondroitin sulphate has been developed by modifying the technique proposed by Yannas et al. (1980). Following experimental successes, the "artificial skin" was applied clinically. It was placed on the skin defects of 10 patients. Three weeks after application the outer layer of silicone sheet was peeled off and thin split thickness skin was grafted onto the newly synthesised dermis-like tissue. Secondary skin grafts took perfectly in all cases and postoperative appearance was satisfactory. PMID- 2107010 TI - Silicone gel including antimicrobial agent. AB - Silicone gel sheets containing Ofloxacin (OFLX), that provide a continual drug delivery system from a wound dressing to the wound so as to prevent infection and to promote healing, are described. It was found that silicone gel sheets without added medication did not inhibit microbial growth but that gel sheets containing 0.02% and 0.2% of OFLX had a positive antimicrobial effect against Staphylococcus aureus and Pseudomonas aeruginosa in a dose-dependent fashion in vitro. Further, this antimicrobial efficacy was greatly increased in a silicone gel sheet that contained 0.02% of OFLX and an additional 10% of silicone oil. In animal experiments, a silicone gel sheet containing OFLX prevented microbiol growth and promoted rapid epithelialisation in wounds to which Staphylococcus aureus had been applied, whereas wounds covered only with OpSite all resulted in continued infection. PMID- 2107011 TI - Pyelocaliceal diverticula and rupture of the kidney. PMID- 2107012 TI - Three-monthly GnRH agonist (buserelin) for prostatic cancer. AB - A new slow release formulation of buserelin given as a 3-monthly depot injection has been evaluated in 4 patients with advanced prostatic cancer previously maintained on shorter acting depots. Treatment was maintained for a mean period of 21 months. Steady state urinary buserelin concentrations were reached by the beginning of the third treatment week and maintained until the end of the third treatment month. Serum testosterone remained suppressed in the castrate range for the duration of the study. Seven previously untreated patients were entered into treatment. Serum testosterone was suppressed into the castrate range between the seventh and fourteenth days after implantation. This preparation offers an advantage for the patient and clinician over existing methods of GnRH analogue administration and will now enter further clinical trial. PMID- 2107013 TI - Profile of ragweed hay fever symptom control with terfenadine started before or after symptoms are established. AB - Forty-two ragweed hay fever patients participated in a study which examined the profile of symptom relief provided by terfenadine, and the relative adequacy of symptom control with the drug given from the beginning of the season compared with treatment started after symptoms were well established. Compared with placebo, terfenadine effectively relieved sneeze, itch and eye symptoms. It had no effect on running, blowing and drainage. Subjectively perceived congestion benefited marginally. When the drug was begun after symptoms were well established, sneezing responded quickly and maximally. Eye discomfort lessened but not to the level experienced by those dosed from the beginning of the season. The pattern in other symptom categories was less clear. Overall, terfenadine improved all rhinitis symptoms except those related to hypersecretion. Some symptoms appeared to respond better when drug dosing commenced at the beginning of the season. PMID- 2107014 TI - The use of parenteral nutrition in calves. AB - Parenteral nutrition has been an important adjunct to therapy of abdominal diseases in calves, with chronic diarrhea and wasting being the most common indication. Parenteral nutrition is administered on a short-term basis to prevent further protein-energy malnutrition in debilitated calves that cannot or will not consume adequate quantities of milk. Parenteral nutrition solutions consist of a protein source (amino acids) and energy sources (glucose and lipid emulsions), supplemented as needed with balanced electrolytes and vitamins. Complications due to PPN are rare, and it is the authors' clinical impression that survivability is enhanced when PPN is employed, although enhanced survivability was not demonstrated in one controlled experimental trial. PMID- 2107015 TI - An introduction to strong ion difference. AB - This brief introduction to strong ion difference represents a fundamental change from the traditional method of understanding acid-base balance. It is hoped that this platform will allow better observation and provide more complete integration of the wide variety of mechanisms that affect homeostasis, from respiratory and renal to hepatic and dietary, and thus provide better outcomes for our patients. PMID- 2107016 TI - Interaction of season and estradiol in the regulation of gonadotropin secretion in the adult ram. AB - The effects of season and estradiol on the secretion of gonadotropic hormones in adult Dorset X Leicester X Suffolk rams were studied. Control groups of intact and castrate rams, and castrate rams given estradiol replacement (approximately 11.5 pg/mL) via polydimethylsiloxane capsules (sc) were assessed for 1 year, beginning in August. Mean concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL) were determined every 2 weeks for all three groups of rams and measurements of testosterone concentration and scrotal circumference were taken on the intact rams. Pulsatile LH release and the LH response to a 2-micrograms dose (iv) of gonadotropin-releasing hormone (GnRH) were assessed for all rams when the testes of intact rams were redeveloped (late October), regressed (early February, late April), and redeveloping (early August). Season directly affected LH-pulse amplitude, which increased only in the control castrate rams between February and April. In October, LH-pulse frequency was the same in both groups of castrate rams, while in April, frequency in the estradiol-treated castrate rams was suppressed to intact ram values. Pituitary responsiveness to exogenous GnRH did not change throughout the year in either of the castrate groups, but along with LH-pulse amplitude, it was increased in August in the intact rams. Although FSH secretion was 14-fold higher in the control castrate rams than in the intact rams, seasonal-directional changes in mean concentration were similar. FSH concentration in the estradiol-treated castrate rams was stable throughout the year. PRL secretion never differed between the control castrate and intact rams but was enhanced in the estradiol treated castrate rams, particularly during long days. PMID- 2107017 TI - Differential response to aminergic stimuli and biological behavior of growth hormone secreting pituitary adenomas. AB - Growth hormone (GH) serum levels in response to the administration of aminergic drugs and thyroliberine (TRH) were determined in a group of 34 acromegalics. Administration of bromocriptine (10 mg single oral dose) was followed by a decrease in GH below 60% control values in 35% of the cases. Administration of diazepam (10 mg single oral dose) to those cases not responding to bromocriptine induced a decrease in GH in 58% of the cases and an increase in GH in 42%. Administration of cyproheptadine (24 mg/day for one month) to those cases not responding to bromocriptine or with increased GH after the administration of diazepam, decreased GH in 75%, while increased GH in 25% of the cases. TRH 200 micrograms single I.V. dose induced increase of 128% GH basal level in 65% of cases (TRH positive) which correlated with more benign clinical course, decreased GH levels in response to bromocriptine, increased PRL levels, PRL-GH mixed secreting adenomas in immunohistochemistry studies, presence of granulated cells in electron microscopy studies and normalization of GH in the majority of surgically treated cases. By contrast, TRH negative cells correlated with aggressive tumor growth, lack of response to bromocriptine, normal PRL levels, pure GH secreting adenomas by immunohistochemistry, poorly granulated cells and lack of response to surgical treatment. Results suggest that there is more than one type of acromegaly that might be distinguished by the aminergic control on GH secretion. PMID- 2107018 TI - Cerebrospinal fluid pressure and prolactin in empty sella syndrome. AB - In 58 female patients with the primary empty sella (PES) syndrome, a study of the CSF dynamics was done by evaluating both the absorptive reserve by a lumbar infusion test at constant rate, and/or the ICP increase occurring during REM phase of nocturnal physiological sleep. In 33, prolactin (PRL) dynamics were also investigated evaluating both the response to sequential stimulating test with thyrotropin-releasing hormone (TRH) and metoclopramide (MCP) and/or the circadian variation of PRL levels. Impairment of CSF dynamics was found in the 84% who had a hormonal pattern characterized by an increase of the PRL response to TRH and MCP and a decrease of the PRL circadian variation. Twenty-one patients with impaired CSF dynamics underwent CSF shunting procedures with disappearance of the signs of intracranial hypertension. They also had restoration of normal PRL dynamics but the endocrine alterations improved only moderately. Altered CSF dynamics play a role in the pathogenesis of the PES syndrome. A correlation between elevated ICP and the hypothalamo-hypophyseal control of PRL secretion may exist. PMID- 2107019 TI - Mupirocin in the treatment of impetigo. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. PMID- 2107020 TI - Containing Ontario's hospital costs under universal insurance in the 1980s: what was the record? AB - In recent years the Ontario government has been concerned that the proportion of public expenditures devoted to health care is at an all-time high. In addition, the media have devoted considerable attention to specific incidents that may represent inadequate funding of hospital services. To shed light on the debate on health care expenditures we analysed the trend in expenditures of Ontario's hospital sector in the 1980s in terms of the amount of inputs (e.g., labour) used to produce hospital services (e.g., a patient-day or admission) and after adjustment for general inflation. As in the 1970s the number of inputs grew relatively slowly during the 1980s. Inputs per patient-day grew at an annual rate of 0.46% and inputs per admission at an annual rate of 2.4%. Cost increases were largely accounted for by hospital wage increases; this could have been due to Ontario's rapidly expanding economy. These findings indicate that Ontario has continued to be successful in containing the number of inputs used in the hospital sector. However, after two decades of substantial success with publicly acceptable cost control, the government faces increased scrutiny as the media and the public focus attention on several areas of perceived inadequate funding in health care services. PMID- 2107021 TI - Histologic changes induced by intraperitoneal chemotherapy with 5-fluorouracil and mitomycin C in patients with peritoneal carcinomatosis from cystadenocarcinoma of the colon or appendix. AB - Intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil has been used to rescue patients from peritoneal carcinomatosis after perforated cystadenocarcinoma of the large bowel or appendix. A staging celiotomy was used to asses the results of therapy. In nine patients tumor was recovered from the abdominal cavity and was subjected to careful histopathologic examination. The posttreatment appearance of the tumor was compared with that before treatment. Also, tumor deposits harvested from these same patients, but from anatomic sites not directly exposed to chemotherapy were examined. The most striking findings observed in treated patients were as follows: (1) the marked reduction in the number of foci of atypical neoplastic epithelium lining the mucin globules, and (2) atrophy and degeneration of the atypical neoplastic epithelium. All treated patients showed these effects but they were not in all sampled tumor specimens, suggesting nonuniform drug distribution in the abdominal cavity and limited penetration of chemotherapy into tumor. The authors conclude that intraperitoneal chemotherapy produces marked histologic changes in mucinous tumors when there is direct contact between tumor and intracavitary drugs. PMID- 2107022 TI - CD4: collaborator in immune recognition and HIV infection. PMID- 2107023 TI - Microtubule MAPping. PMID- 2107024 TI - A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site. AB - HIV infection of chimpanzees results in a chronic viremia unaccompanied by the ultimately fatal immunodeficiency that marks HIV infection in man. We show here that expression of HIV envelope proteins allows syncytium formation between cells expressing human but not chimpanzee or macaque CD4. We find that the CD4 sequences regulating cell fusion lie outside the recognized virus binding site; in the simplest exchange, chimpanzee CD4 bearing human residue 87 supports syncytium formation, while human CD4 bearing chimpanzee residue 87 does not. Neither the equilibrium nor the forward rate constants for HIV-CD4 association are affected by substitution at position 87. Infection of human cells expressing chimpanzee CD4 is insensitive to lysosomotropic agents, suggesting that viral penetration under these circumstances does not require endocytosis. The benign course of HIV infection in chimpanzees may reflect the failure of the host to support direct cell to cell transmission of the virus. PMID- 2107025 TI - Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. AB - p56lck, a lymphocyte-specific member of the src family of cytoplasmic protein tyrosine kinases, is associated noncovalently with the cell surface glycoproteins CD4 and CD8, which are expressed on functionally distinct subpopulations of T cells. Using transient coexpression of p56lck with CD4 or CD8 alpha in COS-7 cells, we show that the unique N-terminal region of p56lck binds to the membrane proximal 10 and 28 cytoplasmic residues of CD8 alpha and CD4, respectively. Two cysteine residues in each of the critical sequences in CD4, CD8 alpha, and p56lck are required for association. Our results suggest a novel role for cysteine mediated interactions between unrelated proteins and provide a model for the association of other src-like cytoplasmic kinases with transmembrane proteins. PMID- 2107026 TI - Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN beta genes. AB - Multimerization of GAAANN generates sequences frequent in virus-inducible promoters. We distinguished different types of (GAAANN)4 sequences mediating virus inducibility. Type I (NN = GT, GC, CT, or CC) responds to IFNs and to IRF-1 and causes silencing. Type II (NN = TG) and type III (NN = CG) neither silence nor respond to IRF-1 or IFN. Type III mediates constitutive transcription and binds the constitutive IEFga factor, whereas type II binds the novel "TG protein". IFN-beta and IFN-alpha 1 promoters contain different response elements: The former has a type I-like sequence (PRDI) and an NF-kappa B-binding sequence (PRDII); the latter has a type II-like "TG sequence" and possibly additional elements but does not bind NF-kappa B. Type I, type II, and NF-kappa B elements represent three distinct terminal pathways mediating virus induction. PMID- 2107027 TI - Developmental regulation of IgM secretion: the role of the carboxy-terminal cysteine. AB - B lymphocytes do not secrete IgM, and plasma cells only secrete IgM polymers. Here we show that both events are attributable to the tailpiece found at the carboxyl terminus of mus chains, and we specifically implicate Cys-575. Thus, if Cys-575 was mutated, IgM was secreted by B cells. Similarly, a mutant IgG containing a mus tailpiece became largely retained within the cell; secretion was restored upon mutation of the tailpiece cysteine. Removal of Cys-575 also allowed hypersecretion of monomeric IgM by plasmacytoma cells. Following further removal of Cmu1, heavy chains were secreted in the absence of light chains. Thus, in B and plasma cells, Cys-575 is involved both in the polymerization of IgM and in intracellular retention of unpolymerized intermediates. PMID- 2107028 TI - Dominant and recessive alleles of the Drosophila easter gene are point mutations at conserved sites in the serine protease catalytic domain. AB - The easter gene, required for the development of all lateral and ventral pattern elements in the Drosophila embryo, appears to encode an extracellular serine protease. Dominant easter alleles increase the number of cells that give rise to lateral and ventral structures. We have found that nine dominant and four recessive mutations are caused by single amino acid substitutions at conserved sites in the putative serine protease catalytic domain. The activity of dominant products was assayed by injecting in vitro synthesized transcripts from the dominant alleles into young embryos. The results suggest that the dominant easter products cleave the normal substrate, but fail to respond to a spatially asymmetric regulator. PMID- 2107029 TI - Inositol 1,4,5-trisphosphate- and arachidonic acid-induced calcium mobilization in T and B lymphocytes. AB - Inositol triphosphate (IP3) formation and increase in intracytoplasmic calcium are mediators of signal transduction in lymphocytes. It has been proposed that IP3 induces Ca2+ release from intracellular stores. It is in order to study the relationship between these two events that we have analyzed the effect of IP3 addition on Ca2+ mobilization in permeabilized resting T and B lymphocytes, EBV-B lymphocytes, and HTLV1-T lymphocytes. IP3 induces a rapid and significant release of Ca2+ from the endoplasmic reticulum in a dose-dependent manner. Ca2+ release is more sensitive to IP3 addition in cycling cells (EBV-B lymphocytes and HTLV1-T lymphocytes) than in resting T and B lymphocytes. Arachidonic acid (AA) induces Ca2+ release from the endoplasmic reticulum (ER) in a manner similar to that of IP3. Neither component has an effect on Ca2+ accumulated in mitochondria, and they have no additive effects suggesting that they act on a similar Ca2+ pool. These results directly demonstrate that in T and B human lymphocytes IP3 mobilizes Ca2+ from ER as in other cellular systems and that other potential second messengers, namely AA, could play a significant role in the internal mobilization of calcium during T and B lymphocyte activation. PMID- 2107030 TI - Monocyte-derived macrophage and alveolar macrophage fibronectin production and cathepsin D activity. AB - Alveolar macrophages are thought to play an important role in ongoing tissue breakdown and repair processes in the normal lung. The secretion and regulation of cathepsin D (important for the final breakdown of collagen) and fibronectin (involved in the healing process) in human peripheral blood monocytes (PBM) and pulmonary alveolar macrophages (PAM) were investigated. Cathepsin D enzyme activity was measured by quantitating the TCA-soluble fragments of [3H]hemoglobin. Freshly isolated PBM contained less cell-associated cathepsin D activity than did freshly isolated PAM (314 +/- 35 micrograms/10(6) cells vs 381 +/- 35 micrograms/10(6) cells, respectively). After 7-10 days in culture, cell associated enzyme levels in both PBM and PAM were significantly increased (P less than 0.001 for PBM; P less than 0.0001 for PAM). In addition, freshly isolated PAM secreted more cathepsin D than did freshly isolated PBM (5.8 +/- 3.2 micrograms/10(6) cells vs 0.83 +/- 0.83 micrograms/10(6) cells, P less than 0.02). In the presence of LPS (10 micrograms/ml), cell-associated cathepsin D was inhibited in both PBM and PAM. With the addition of gamma-IFN (500 U/ml), both cell-associated and secreted enzyme were increased in freshly isolated and 10-day cultured PBM and PAM. In parallel studies, fibronectin secretion (by ELISA assay) in both PBM and PAM increased over time in culture. LPS had no effect on PBM or PAM secretion of human fibronectin while gamma-IFN increased PBM and PAM fibronectin levels. Thus, both macrophage cathepsin D activity and fibronectin secretion are increased by gamma-interferon while macrophage cathepsin D activity, but not fibronectin secretion, is decreased by LPS. These studies demonstrate that human macrophage cathepsin D activity is actively modulated by inflammatory mediators and that macrophage mediators of tissue breakdown and repair are not modulated synchronously. PMID- 2107031 TI - Morphine-induced immune alterations in vivo. AB - The high incidence of human immunodeficiency virus (HIV) seropositivity among drug abusers prompted us to examine in an animal model the effects of morphine on aspects of the immune system that may be specifically related to HIV infection. We now report a robust, sustained elevation in the ratio of CD4+/CD8+ cells in the spleen and thymus of mice chronically treated with morphine. Since CD4+ cells have been reported to be target cells for HIV, these alterations, in concert with a marked cellular atrophy that appears to be restricted to organs of the immune system, suggest that opiates may serve as cofactors in altering the immune status of the host and thus contribute to the increased susceptibility to HIV infection and eventual development of AIDS in opiate abusers. PMID- 2107032 TI - Differential effects of copper and zinc on human peripheral blood monocyte cytokine secretion. AB - The addition of copper and zinc salts to human peripheral blood leukocytes cultured in complete medium containing endotoxin and fetal calf serum stimulated tumor necrosis factor (TNF) secretion in a concentration-dependent manner. The secretion of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) was inhibited by copper under the same culture conditions, while zinc stimulated IL-1 beta secretion in a concentration-dependent manner and had no effect on leukocyte IL-6 release. Both copper and zinc induced increases in TNF mRNA (54 and 14%, respectively) when compared to cells cultured in complete medium alone. In serum free, low endotoxin medium (less than 6 pg/ml), both copper and zinc failed to stimulate either TNF or IL-1 beta secretion. Under the same conditions the addition of lipopolysaccharide (LPS), at concentrations above 0.01 micrograms/ml, induced a concentration-dependent release of both cytokines. When either copper or zinc were combined with 0.01 micrograms/ml LPS, a synergistic stimulation of TNF secretion resulted. IL-1 beta secretion, unlike TNF, was not synergistically stimulated by combining metals and LPS in serum-free medium. Combining copper and zinc with inhibitors of TNF secretion, transforming growth factor beta, prostaglandin E2, and plasma alpha-globulins, resulted in a reduction of the suppressive effects of each of these agents. This study suggests that the trace metals copper and zinc may play important and possibly distinct roles in regulating leukocyte secretion of TNF, IL-1 beta, and IL-6. PMID- 2107033 TI - Effects of brain microtubule-associated proteins on microtubule dynamics and the nucleating activity of centrosomes. AB - In this paper, we report on the effect of brain microtubule-associated proteins (MAPs) on the dynamic instability of microtubules as well as on the nucleation activity of purified centrosomes. Under our experimental conditions, tau and MAP2 have similar effects on microtubule nucleation and dynamic instability. Tau increases the apparent elongation rate of microtubules in proportion to its molar ratio to tubulin, and we present evidence indicating that this is due to a reduction of microtubule instability rather than to an increase of the on rate of tubulin subunits at the end of growing microtubules. Increasing the molar ratio of tau over tubulin leads also to an increase in the average number of microtubules nucleated per centrosome. This number remains constant with time. This suggests that the number of centrosome-nucleated microtubules at steady state can be determined by factors that are not necessarily irreversibly bound to centrosomes but, rather, affect the dynamic properties of microtubules. PMID- 2107034 TI - Specific drug binding to rat liver cytochrome P-450 isozymes induced by pregnenolone-16 alpha-carbonitrile and macrolide antibiotics. Implications for drug interactions. AB - Clinical interactions of macrolides with various drugs lead to elimination impairment, increase of plasma concentration and overdose-like effects, resulting from modifications of their metabolism. Previous studies have shown that treatment of rats by the macrolide antibiotics of the oleandomycin and erythromycin series lead to the induction of an hepatic cytochrome P-450 which is implicated into their own metabolism. We have characterized PCN or macrolides induced cytochromes P-450 by their specific ability to interact with macrolide derivatives and, using the cytochrome P-450 spectral binding assays, we have shown that some compounds, implicated in drug interaction with macrolides, interact preferentially with the same cytochromes. This strongly suggests that specific blockage of cytochrome P-450 IIIA1 family by macrolides, is responsible for these drug interactions and that these interactions can be predicted easily by simple in vitro tests such as those described herein. PMID- 2107035 TI - [Effect of peroxyacetic acid disinfection using an aerosol spray method]. PMID- 2107036 TI - Hyperbaric oxygen and CO2 embolism. PMID- 2107037 TI - Base and sequence specificities of aflatoxin B1 binding to single- and double stranded DNAs. AB - The inhibitory effect of alfatoxin B1 (AFB1) on the template function for RNA synthesis of several single- and double-stranded DNAs with known base content and sequence was studied in vitro. The results showed that AFB1 strongly inhibits the template function of poly[d(G-C)] and has little, if any, effect on poly[d(A-T)]. Using [3H]AFB1 for the binding, and by spectrum analysis of the appearance of a broad AFB1-DNA adduct peak between 300 and 400 nm right after the typical DNA peak at 260 nm, it is possible to conclude that the binding preference of AFB1 to DNA is: poly[d(G-C)] greater than polydG.polydC greater than polydG greater than polydC, with no detectable binding to poly[d(A-T)]. These studies have therefore provided evidence that the selective inhibition of DNA template function is a direct reflection of the binding specificities of AFB1 to DNA. Furthermore, since there is a 3-fold binding preference of AFB1 for poly[d(G-C)] over polydG.polydC on an equal weight basis, and with very low binding affinity toward either G or C when it is in single-stranded form, these data also suggest: (i) AFB1 binds preferentially to DNA with an alternating G-C sequence compared to DNA with a sequence of contiguous Gs or Cs; and (ii) intercalation may be part of the mechanism for the binding of AFB1 to DNA. PMID- 2107038 TI - Growth-hormone-releasing hormone. AB - Growth-hormone-releasing hormone (GHRH, somatoliberin) is the hypothalamic peptide hormone that specifically stimulates synthesis and release of growth hormone (GH, somatotropin) by somatotrope cells of the anterior pituitary gland. GHRH is the last of the classically postulated hypothalamic hormones to be characterized, synthesized, and used in clinical medicine. In this review of GHRH, I discuss the discovery and characterization of the peptide, its role in the regulation of GH secretion, and its clinical use in pathological states of GH excess and GH deficiency. The two most clinically useful aspects of GHRH are to establish the etiology of GH deficiency, most commonly the result of a hypothalamic GHRH deficiency, and to treat GH-deficient children. Use of GHRH as therapy for GH deficiency currently is experimental and, to date, results encourage the idea of a therapeutic role for this peptide in promoting endogenous GH secretion with resulting acceleration of linear growth. PMID- 2107039 TI - Differentiating various abnormalities of thyroxin binding to serum proteins by radioelectrophoresis of thyroxin and immunoassay of binding proteins. AB - Using the simple method of protein analysis described here, we could identify thyroxin (T4)-binding-protein abnormalities in euthyroid patients with hyperthyroxinemia or hypothyroxinemia. Serum incubated with [125I]thyroxin was analyzed by agarose gel electrophoresis, with bromphenol blue staining of protein. The relative distribution of radioactive T4 was determined for each binding protein--thyroxin-binding globulin (TBG), transthyretin, albumin, and T4 binding immunoglobulin (when present)--and the mass of T4 bound to each was determined. We also used sensitive immunoassays to quantify TBG, transthyretin, and albumin concentrations, then calculated the mass of T4 (as determined by electrophoresis) bound per unit mass of the respective binding protein. When the concentration of binding proteins was altered (e.g., TBG excess or TBG deficiency), the T4 binding/mass ratio for each protein remained within the expected range; but when the functional affinity of a binding protein was altered -as in dysalbuminemic hyperthyroxinemia and in low-T4 nonthyroidal illness--this ratio was abnormal. This procedure can be used to help identify TBG excess, TBG deficiency, dysalbuminemic hyperthyroxinemia, prealbumin-associated hyperthyroxinemia, variant TBG with reduced affinity for T4, euthyroid sickness, and T4-binding autoantibodies. PMID- 2107040 TI - Light-chain ratios of immunoglobulins G, A, and M determined by enzyme immunoassay. AB - We describe an enzyme-linked immunosorbent assay for determination of light-chain ratios for IgG, IgA, and IgM in serum. A commercial serum with known overall kappa and lambda concentrations was used as standard. To capture the respective immunoglobulins, we used antibodies to gamma, lambda and mu chains coated onto microtiter plates. Peroxidase-conjugated anti-kappa and anti-lambda chain antisera were reacted with light chains on the captured immunoglobulins, and the amount of enzyme bound was monitored with o-phenylenediamine and urea-hydrogen peroxide as substrates. Calculation of absorbance ratios allowed determination of kappa and lambda chain concentrations of individual immunoglobulins in the standard and samples. Within-run and between-run CVs (n = 25) ranged from 5.9% to 13.0% for "high," "normal," and "low" kappa/lambda ratios for IgG, IgA, and IgM. The thoroughness of light-chain detection, expressed as, e.g., (IgA kappa + IgA lambda)/(total IgA), for 150 sera was 91-110%. The detection limit was 1 microgram/L. Reference intervals (mean +/- SD) for kappa/lambda ratios in sera from 100 apparently healthy adults were 2.34 +/- 0.80 for IgG, 1.59 +/- 0.40 for IgA, and 1.86 +/- 0.76 for IgM. PMID- 2107041 TI - A study of the CEDIA digoxin immunoassay. AB - We evaluated the CEDIA digoxin immunoassay (Microgenics, Inc., Concord, CA), as performed with the Cobas-Bio centrifugal analyzer. In assays of sera with known concentrations of digoxin, the enzyme activity, measured when two beta galactosidase (EC 3.2.1.23) fragments were combined according to the assay format, was proportional to the digoxin concentration. Results of assays of sera containing 0 to 3 micrograms of digoxin per liter correlated well when compared with an RIA method: CEDIA, microgram/L = 1.00 x RIA - 0.06 microgram/L (n = 90, r = 0.95, Sxy = 0.05). Duplicate assays of three control sera containing 0.8, 2.2, or 3.3 micrograms/L, each analyzed 20 times a day with each group of patients' samples, gave within-run CVs of 1-3% and day-to-day CVs of 3-12%. The reconstituted CEDIA reagents were stable for at least a month at 5 degrees C. As many as 25 samples and controls can be assayed in half the time needed to complete a similar number of RIA measurements with comparable results. PMID- 2107042 TI - Role of the clinical laboratory in guiding treatment of Amanita virosa mushroom poisoning: report of two cases. AB - Historically, mortality after Amanita mushroom ingestion has ranged from 50% to 90%. Prompt diagnosis is imperative, and aggressive therapeutic measures must be instituted quickly to improve the outcome. We report successful treatment of two cases of A. virosa poisoning by use of combined therapies, including thioctic acid and hemoperfusion. PMID- 2107043 TI - Accuracy of Reflotron cholesterol assays evaluated. PMID- 2107044 TI - Transitory deficit in high-density lipoproteins and apolipoprotein A-I. PMID- 2107045 TI - Histochemical, ultracytochemical and biochemical study of alkaline phosphatase activity during gastric carcinogenesis. PMID- 2107046 TI - Mental retardation, craniofacial dysmorphism, hypogonadism, diabetes mellitus and epilepsy in four siblings. A "new" mental retardation syndrome. AB - In this report we describe a distinct and apparently new mental retardation syndrome in four siblings: three brothers and one sister. They present slight to moderate mental retardation associated with a peculiar craniofacial dysmorphism (4/4), hypergonadotrophic hypogonadism (4/4), eunuchoid habitus (4/4), diabetes mellitus (4/4) and epilepsy (3/4). PMID- 2107047 TI - The phakomatoses as paracrine growth disorders (paracinopathies). AB - A microcomputer database management system retrieved all 170 probands with phakomatoses evaluated through the genetic clinics at the University of South Florida between January 2, 1982 and December 31, 1987. Neurofibromatosis (NF) was the diagnosis of 118 of them; 42 had other phakomatoses and 10 had transitional phenotypes difficult to classify. The analysis of the hamartomas of all probands indicated disorganized differentiation and overgrowth of cell species characteristic for the involved tissue and location. Abundance of extracellular fibrillary components was also evident in most hamartomas. Adequate blood supply was a conditio sine qua non. This was seen in monogenic, sporadic, transitional and combined phakomatoses alike and implied a common pathogenesis. The paracrine growth factors and their regulation emerged as the most plausible common denominator for the pathogenesis. A unitary pathogenetic hypothesis is proposed that the phakomatoses represent paracrine growth regulation disorders (paracrinopathies). Conditions such as fibromatoses, lipomatoses, lipodystrophies, hemihyper/hypotrophies, including Russell-Silver and Beckwith Wiedemann syndromes may be proven to be paracrinopathies as well. PMID- 2107048 TI - Stimulation of the respiratory burst and promotion of bacterial killing in human granulocytes by intravenous immunoglobulin preparations. AB - We have examined the effect of two i.v. immunoglobulin preparations on the metabolic and functional activities of neutrophil granulocytes from the peripheral blood. Production of superoxide anion (O2-) by granulocytes was measured through superoxide dismutase inhibitable reduction of ferricytochrome C after incubation of cells for various times together with immunoglobulin (concentration ranging from 0.25 to 5.0 mg/ml). The results showed dose-dependent response of O2- production independent of the incubation time. Granulocytes containing ingested Staphylococcus aureus released a significantly (P less than 0.001) larger amount of O2- and killed a higher number (P less than 0.001) of viable bacteria in the presence of 5 mg/ml immunoglobulin than did cells incubated in the absence of extracellular i.v. immunoglobulin. These data raise the possibility that immunoglobulin concentrates for i.v. use may enhance the anti-bacterial activities of phagocytic cells through direct stimulation of the respiratory burst. Inflammatory reactions observed during i.v. immunoglobulin infusion in hypo- or agammaglobulinaemic patients may also be related to phagocytic cell activation. PMID- 2107049 TI - Cytokines, thyroid autoantibody synthesis and thyroid cell survival in culture. AB - In autoimmune thyroid disease lymphoid cells infiltrating the thyroid gland occur in conspicuous aggregates or as a diffusely distributed population invading the thyroid follicles. Consequently cytokines secreted by activated T cells or macrophages could influence neighbouring thyroid cells as well as other lymphocytes. We have investigated this possibility using recombinant cytokines. Thyroid cell survival was assessed in terms of mitochondrial dehydrogenase activity in monolayers exposed to tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1 (IL-1 alpha and beta) and interleukin 2 (IL-2) in the presence or absence of thyroid-stimulating hormone (TSH). Neither TNF-alpha nor IL-2 affected thyroid cell survival, IFN-gamma was usually inhibitory and IL-1 alpha slightly enhanced cell survival in some experiments. However, the effects were small and variable and were not enhanced by potentially synergistic combinations of cytokines, longer periods of exposure, or different culture conditions. In contrast, IFN-gamma, IL-2 and TNF-alpha inhibited the ability of thyroid lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis to synthesize autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg). Comparison of lymphoid populations isolated by digestion and/or mechanical disaggregation indicated that a population of activated B cells, plasma cells and T cells, intimately associated with thyroid cells since they could only be extracted by digestion, was influenced by cytokines. Our studies suggest that in addition to its well-recognized ability to induce MHC class II antigens on thyroid cells, IFN-gamma may inhibit thyroid cell proliferation and TNF-alpha, IFN-gamma and IL-2 may down-regulate thyroid autoantibody synthesis. PMID- 2107050 TI - Plasminogen activator inhibitor 1 in renal fibrin deposits of human nephropathies. AB - The persistency of fibrin deposits in the kidney during renal diseases could reflect either a defective release of plasminogen activators (PA) or a local excess of PAI. In order to investigate this question, we studied human renal biopsies by immunofluorescence technique with specific antibodies for fibrin, tissue-type plasminogen activator (t-PA), urokinase (u-PA), PAI-1 and PAI-2. By this technique t-PA could be detected in the glomerular flocculus and the endothelium of small arteries of the normal control kidneys. We failed to detect significant fluorescence with other antibodies in normal kidneys. Conversely, in cases of vascular nephropathy with thrombosis the positive fluorescence obtained with anti-fibrin antibodies at the site of thrombosis was associated with a positive fluorescence with anti-PAI-1 and to a lesser extent with anti-t-PA antibodies. u-PA and PAI-2 were not detected in these lesions. Similarly in the most severe forms of crescentic glomerulonephritis, extracapillary fibrin deposits were associated with PAI-1. In one case u-PA was also detected. This is in agreement with our previous findings that glomerular epithelial cells release both PAI-1 and the inactive form of u-PA (pro u-PA). Thus, our results support the hypothesis that PAI-1, which is able to inhibit both t-PA and u-PA, may play a major role in the persistency of fibrin deposits in the human kidneys during pathological conditions. PMID- 2107051 TI - Immunohistochemical characterization of glomerular IgA deposits in IgA nephropathy. AB - To characterize the IgA deposits found in glomeruli of IgA nephropathy, frozen sections of renal biopsy specimens from 191 consecutive patients with IgA nephropathy were examined by immunofluorescent microscopy. All 191 specimens were positive for IgA1 in glomeruli. IgA2 was detected in 3 out of these 191 specimens. Both kappa and lambda light chains were also detected in the glomeruli of all specimens. The presence of J chain was represented in 113 specimens after acid-urea pretreatment. Secretory component (SC) was detected in 13 out of the 191 specimens, but not in controls. Both J chain and SC were detected in 2 out of 3 specimens positive for IgA2 but not for IgM. These results suggest that IgA deposited in glomeruli in some patients with IgA nephropathy is perhaps mucosally derived IgA. PMID- 2107052 TI - Changes in plasma follicle-stimulating hormone, luteinizing hormone, estrogen and progesterone during growth of ovulatory follicles in the pig. AB - This experiment was conducted to determine the changes in secretion of LH, FSH, estrogen and progesterone during follicle maturation. Ovaries were recovered from 11 non-treated (control) gilts, three on day 13, four on day 16, and four on day 19 of the estrous cycle, and from four altrenogest-treated gilts on day 19. Altrenogest, a progesterone agonist, was fed at a dose of 20 mg once daily from days 13 to 18 to block spontaneous follicle maturation. Gilts were bled daily from day 12 until slaughter. For control gilts, the number of follicles/gilt 1-6 mm in diameter decreased (P less than .05) from 93.5 on day 13 to 21.5 on day 19, and the number of large (greater than 6 mm) follicles increased (P less than .05) from 5.3 to 13.2. Altrenogest treatment blocked loss of small follicles and growth of large follicles between days 13 and 19. Plasma progesterone decreased (P less than .001) between days 12 and 16 in both control and altrenogest-treated gilts. Plasma FSH decreased (P less than .05) between days 12 and 16 only in control gilts. Plasma LH was not significantly affected by day or altrenogest treatment. Plasma estrogen increased (P less than .05) between days 15 and 19 only in control gilts. These results indicate that 1) no increased LH secretion was detected in conjunction with emergence of ovulatory follicles, and 2) atresia of nonovulatory follicles was associated with decreased secretion of FSH. Both atresia and decreasing FSH secretion began before estrogen concentration increased in the systemic circulation. PMID- 2107053 TI - Insulin-like growth factor-I concentration in Holstein female cattle: variations with age, stage of lactation and growth hormone-releasing factor administration. AB - Plasma insulin-like growth factor-I (IGF-I) concentrations were monitored in Holstein females through different periods of their growth, lactation and after acute or chronic growth hormone-releasing factor (GRF) administration. Plasma samples were radioimmunoassayed using a human IGF-I antibody after a 24 hr incubation in a HCl(.1N)-glycine(.2M) buffer (pH 2). In a first study, IGF-I concentrations were measured in Holstein females of different ages and(or) stages of lactation (n = 6 per group). The IGF-I concentrations in newborn calves (102.0 +/- 11.3 ng/ml) markedly decreased (P less than .01) in 1 mo old animals (50.2 +/ 7.1 ng/ml), then increased (P less than .01) to 137.0 +/- 5.1 and 137.4 +/- 11.0 ng/ml in 6 and 10 mo old heifers, respectively. In dairy cows, IGF-I concentrations were low 24 hr post-partum (44.7 +/- 7.6 ng/ml) and then increased (P less than .05) to remain stable throughout lactation (91.3 +/- 4.9, 92.8 +/- 12.9, 96.1 +/- 7.6, 90.7 +/- 8.8 ng/ml at 2, 3, 6 and 9 mo of lactation, respectively). There was a further increase (P less than .05) to 113.7 +/- 3.1 ng/ml during the dry period. In a second trial, blood samples were collected from lactating dairy cows every 2 hr for 24 hr following a sc injection of saline (n = 4) or human (h) GRF (1-29)NH2 (10 micrograms/kg BW, n = 4). The IGF-I peak concentration was reached on average 10 hr after the GRF injection and was higher (P less than .01) in treated cows than in control cows (135.4 vs 86.9 +/- 16.2 ng/ml). In the last trial, daily sc injections of 10 micrograms of hGRF(1-29)NH2 per kg BW to dairy cows (252 days of lactation) for 57 days, which increased milk production by 14% (2 kg/day), also increased (P less than .01) IGF-I concentration: 127.1 +/- 5.3 and 118.0 +/- 1.6 vs 90.7 +/- 4.7 and 96.0 +/- 5.0 ng/ml on days 29 and 57 of treatment for treated (n = 9) and control (n = 8) cows, respectively. Thus, the IGF-I concentration in dairy cattle varies with age and stage of lactation, and is increased by GRF administration in lactating dairy cows. PMID- 2107054 TI - Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. I. Contraceptive efficacy and side effects. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation. AB - A multicentre clinical trial, including 19 centres in 13 countries, assessed the contraceptive efficacy and clinical acceptability of a Silastic 382 vaginal ring releasing 20 micrograms of levonorgestrel for at least 90 days. A total of 1005 women entered the study and 8176.74 woman-months of experience was gathered. The rate of intrauterine pregnancy at one year of use was 3.6 per 100 women (95% confidence interval 2.2-5.0), and of ectopic pregnancy, 0.2% (one case). The principal reasons for discontinuation were menstrual disturbances (17.2% at one year), vaginal symptoms (6.0%) and repeated expulsion of the ring (7.1%). The pregnancy rate with this 20 micrograms levonorgestrel-releasing vaginal ring compares favourably with that of a low estrogen combination oral contraceptive tested by WHO and is less than half that of a progestogen-only oral contraceptive in a WHO randomized study. It is concluded that the WHO intravaginal ring releasing an average of 20 micrograms of levonorgestrel per 24 hours is an effective method of contraception for at least one year of use. PMID- 2107055 TI - Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. II. Expulsions and removals. World Health Organization. Task Force on Long Acting Systemic Agents for Fertility Regulation. AB - This paper investigates the relationship between expulsions and removals, and demographic characteristics of 1005 women from 19 centres using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. Emphasis is placed on discontinuations of method use due to expulsions, on the number and rate of expulsions, and the time at which the first expulsion occurred. The overall life table discontinuation rate due to expulsion was 7.1% at one year. Life-table discontinuation rates increased with parity and were highest in Asian and lowest in European women. In respect to the number of expulsions experienced by women (expulsions did not necessarily lead to discontinuation), the women of high parity and those from Asia and Europe have the highest rates. The life-table first expulsion rate is 29% at one year. Such rates are highest in Chinese and Asian women. Following a first expulsion, the second expulsion rate is 45% by the end of the subsequent six months. The majority of first expulsions occur at defaecation (134 or 57% of 234 women), urination (12%) and during menstruation (17%). Rings were removed by 121 (12%) women on 201 occasions and for a variety of reasons. The main medical reasons were vaginal discharge and irritation, bleeding pain and dyspareunia. Others removed the ring during defaecation, intercourse or because the ring came out of place. Women also removed rings for curiosity, to show their husbands and to clean. PMID- 2107056 TI - Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. III. The relationship between pregnancy rate and body weight. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation. AB - This paper investigates the relationship between pregnancy rates and body weight of 1005 women using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. While the overall pregnancy rate at one year was 3.7%, it was found that women have an increasing risk of pregnancy with increasing body weight. For example, a woman of 40 kg has an estimated pregnancy rate of 1.7% in contrast to 9.8% for a woman of 80 kg weight. PMID- 2107057 TI - Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. IV. Bleeding patterns. World Health Organization. Task Force on Long Acting Systemic Agents for Fertility Regulation. AB - A multicentred clinical trial was conducted in 12 countries to assess the contraceptive efficacy and side effects of a low-dose levonorgestrel-releasing vaginal ring. Contraceptive efficacy and side effects, expulsions and removals, and the relation between pregnancy rate and admission body weight of the women have been reported previously. The effect of ring use on vaginal bleeding patterns as observed from daily menstrual diaries kept by the women is the object of this paper. A total of 1005 women were fitted with the ring and 702 of them provided a menstrual diary suitable for analysis. The description of the bleeding patterns is made using a 90-day reference period approach and following the guidelines published by WHO. In addition the longest bleeding/spotting episode and longest bleeding/spotting-free interval are calculated over the entire diary length. Half of the ring users have vaginal bleeding patterns similar to normal untreated patterns. A quarter experience irregular bleeding, 10% have prolonged cycles and 10% have shortened cycles. Over one year of continuous use, there appears to be no significant trend in these patterns. Users with the worst bleeding patterns tend to discontinue first during the clinical trial and are influenced by their more recent experience of vaginal bleeding irregularities. Life-table analysis of discontinuation rates gives an underestimation of the true incidence of bleeding irregularities. Some comments are made on the limitations of the methods of analysis of menstrual diaries. PMID- 2107058 TI - Ovarian endocrine function through five years of continuous treatment with NORPLANT subdermal contraceptive implants. AB - Ovarian endocrine function was assessed in 88 women using NORPLANT subdermal implants during different periods of use and in a control group of 15 women using non-hormonal contraception. Blood samples for estradiol (E2) and progesterone (P) assays were obtained twice a week for five consecutive weeks. Three distinct E2 patterns were observed: one was characterized by fluctuating levels within a normal range (20 to 400 pg/ml), a second pattern corresponded to continuous low E2 levels (below 75 pg/ml in the 10 samples) and the third was characterized by high broad estradiol peaks reaching over 400 pg/ml. The proportion of sampling runs characterized by normal fluctuating levels increased from 38% in the first two years of use to 80% during the fifth year of use. Low E2 profile was only observed during the first two years of use (27%) and in only 1 case at the beginning of the third year of use (5%). The percentage of cycles with high broad estradiol peaks remained between 20-40% without a clear tendency to change in either direction with duration of use. Thirty-three percent of the observed sampling runs had luteal activity (P above 3 ng/ml). The proportion of runs with luteal activity increased from 14% during the first two years of use to 40% during the third and fourth, and 60% during the fifth year of use. All control subjects had luteal activity. The mean highest progesterone level was lower in the NORPLANT runs (8.7 +/- 3.9 ng/ml) as compared to the controls (11.3 +/- 3.8 ng/ml). NORPLANT sampling runs with luteal activity had normal fluctuating E2 levels with only one exception. However, not all cycles with normal E2 levels showed luteal activity. On the other hand, all runs with low E2 levels or high broad E2 peaks were without luteal activity. In summary, women using continuous low-dose levonorgestrel contraception through NORPLANT subdermal implants, have a variable degree of ovarian activity as compared with the more complete depression of ovarian function observed among pill or injectables' users. Ovarian activity becomes closer to normal during the third through fifth year of use. PMID- 2107059 TI - The effects of 5% carbon dioxide on the quantitative analysis of long-term pathology of the brain after surface hypothermia. AB - To evaluate the effects of 5% carbon dioxide (CO2) administration for hypothermic circulatory arrest, neurological evaluation and pathological studies were carried out on the canine brain. Twenty-two dogs were assigned to five groups: Group 1: Three dogs without hypothermia were sacrificed as the control group. Group 2: Nine dogs were subjected to surface hypothermia (20 degrees C) under deep ether anesthesia with 100% oxygen (O2) and hyperventilation. Circulatory arrest time was 30 min in Group 2A and 60 min in Group 2B. Group 3: Ten dogs were surface cooled (20 degrees C) under deep ether anesthesia with a 95% O2 and 5% CO2 mixture. Thirty minutes of circulatory arrest was instituted in Group 3A and 60 min in Group 3B. Dogs in Groups 2 and 3 were surface rewarmed and kept alive until they were sacrificed electively 6 or more months later. Results were as follows: (i) Postoperative neurological disturbance was detected in only two dogs in Group 2B. (ii) The percentage of damaged nerve cells among the total nerve cells counted in the cerebral cortex of the frontal lobe was significantly greater in Groups 2A (22.4%), 2B (30.1%), 3A (19.6%), and 3B (22.2%) compared with Group 1 (7.1%). (iii) The number of glia cells per nerve cell in the cerebellar dentate nucleus was significantly higher in Group 2B (27.2) than in Groups 1 (11.8), 2A (16.7), 3A (17.9), and 3B (18.6). (iv) The number of Purkinje cells in a 10-mm length of the cerebellum was markedly reduced to 89 in Group 2B compared with 122, 134, and 117 in Groups 1, 2A, and 3A, respectively. In conclusion, the results of quantitative pathological brain analysis reflected the incidence of postoperative neurological disturbance and suggested that the administration of 5% CO2 could prolong the time limit for circulatory arrest. PMID- 2107060 TI - Double-blind, placebo-controlled, multi-centre trial of the efficacy and tolerance of niflumic acid ('Nifluril') capsules in the treatment of tonsillitis in adults. AB - A double-blind, placebo-controlled study was carried out in 231 adult patients suffering from acute diffuse pharyngitis or acute tonsillitis with fever and dysphagia to assess the effectiveness of niflumic acid combined with standard antibiotic therapy in relieving pain and inflammation. Patients were allocated at random to receive either 4 capsules of 250 mg niflumic acid or placebo daily in addition to 1.5 million units phenoxymethyl penicillin for 4 to 5 days. Clinical assessments before and after 2 and 4 days of treatment showed that there was faster resolution of fever, pain, adenopathy, pharyngeal congestion and dysphagia, and improved patient comfort in the niflumic acid group. Few side effects were recorded and there were only 4 drop-outs due to side-effects in patients receiving niflumic acid. PMID- 2107061 TI - Head injuries in the pediatric population. PMID- 2107062 TI - Modulation of portosystemic shunting by prostacyclin in portal hypertension. PMID- 2107063 TI - Whirlpool folliculitis: a review of its cause, treatment, and prevention. AB - Folliculitis caused by Pseudomonas aeruginosa has been increasing due to the popularity of hot tubs, swimming pools, and whirlpools. The follicular pustules and inflammatory papules usually occur after an incubation period of two to four days and improve spontaneously in seven to ten days. Despite the discomforts of the condition, treatment is usually not necessary and may even prolong the infection. Since it is difficult to control the growth of Pseudomonas in hot tubs and whirlpools, attention to water conditions is the best way to prevent this irritating skin condition. PMID- 2107064 TI - In vivo evaluation of a dual-action antibacterial, Ro 23-9424, compared to cefotaxime and fleroxacin. AB - The dual-action antibacterial R 23-9424 (desacetylcefotaxime linked to the quinolone fleroxacin) is a new antibacterial agent with excellent in vitro activity. It was evaluated for in vivo efficacy in comparison with the cephalosporin cefotaxime and the quinolone component, fleroxacin. Ro 23-9424 demonstrated significant activity against all strains tested in systemic infections, including those strains resistant in vivo to cefotaxime (Staphylococcus aureus 753, Serratia marcescens SM and Pseudomonas aeruginosa 8780) and fleroxacin (Streptococcus pneumoniae 6301 and Streptococcus pyogenes. In prophylactic studies, Ro 23-9424 compared favorably with fleroxacin against Escherichia coli and with cefotaxime against S. pyogenes, but Ro 23-9424 was considerably more active than cefotaxime against E. coli and more active than fleroxacin against S. pyogenes. In a murine pneumonia model, Ro 23-9424 was equivalent in activity to cefotaxime against S. pneumoniae and more active than cefotaxime against Klebsiella pneumoniae. Fleroxacin was inactive against S. pneumoniae and about 20-fold more active than Ro 23-9424 against K. pneumoniae. In a murine meningitis infection caused by S. pneumoniae, Ro 23-9424 was 3 times as active as cefotaxime, while fleroxacin was inactive. When meningitis was induced by K. pneumoniae, Ro 23-9424 was as active as the quinolone, while cefotaxime was inactive. In a neutropenic (immunocompromised) model, Ro 23-9424 was more active than cefotaxime against P. aeruginosa and 5-fold less active than fleroxacin. In the control normal (immunocompetent) mouse infection, Ro 23-9424 was 3-fold more active than cefotaxime, but 10-fold less active than fleroxacin. PMID- 2107065 TI - Studies of the maintenance of subsidized foster placements in the Casey Family Program. AB - The Casey Family Program provides a planned, long-term approach to subsidized foster care for the underachievers of the child welfare system. Its concept is a marriage of what foster care professionals know about effectively helping children and what managers know about effectively running organizations. The purpose of our studies of The Casey Family Program was to determine whether the outcomes of its foster placements were predictable from factors that could be known, at least in principle, at the time the placements were made. We built statistical models of placement maintenance based upon characteristics of (a) the foster child; (b) his or her biological family; and (c) the foster family. We used two main sources of data to construct models: archival material on the child and his or her biological family, and caseworker ratings of various aspects of the child and his or her foster family. Information was derived from a sample of 51 children served by the Montana Division of The Casey Family Program to build the models, which in general provided accurate predictions of placement outcomes. The models were then cross-validated with a sample of 55 children from the Idaho Division. There was a substantial amount of shrinkage in the variance accounted for in the cross-validation sample, but outcomes remained largely predictable. To determine whether predictions of placement outcomes could be based upon brief assessments of factors that could be evaluated at the time placements were made, a third study was undertaken. The results of that study implied that ratings of salient characteristics of foster children and foster families based upon as little as a single day's observation could be used to effectively predict placement outcomes. Several aspects of these studies deserve special emphasis. First, the research confirmed that the children served by the Montana and Idaho divisions of TCFP were among the underachievers of the child welfare system whom Jim Casey desired to reach. It also confirmed that the Montana and Idaho divisions were doing an effective job of serving those children. Their placements were generally stable and both foster children and foster families were rated as functioning at levels that ranged from acceptable to good.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2107066 TI - [Ulcer disease--drug treatment and its limitations]. PMID- 2107067 TI - [Splenic artery aneurysm and diverticulum of the small intestine. A rare combination]. PMID- 2107068 TI - [Extensive intramural diverticulum formation of the esophagus. 41 years following lye chemical burn]. PMID- 2107069 TI - [Guillain-Barre polyneuropathy in Wegener's granulomatosis with pulmonary-renal syndrome]. AB - A 49-year-old female patient suffering from severe necrotising respiratory granulomatosis (Wegener's granulomatosis) had acute renal failure, nearly uncontrollable haemoptyses and severe deterioration of pulmonary function. Haemodialysis had to be performed; immuno-suppressive therapy was effected by administration of high doses of methylprednisolone (100-500 mg/d) and cyclophosphamide (initially with single doses of 500-1000 mg) and plasmaphereses. Artificial ventilation by positive-negative pressure breathing became necessary because pulmonary function became consistently poorer. Glucocorticoid therapy led to the development of several duodenal ulcers resulting in profuse gastrointestinal bleedings requiring transfusions; on the whole, 20 erythrocyte concentrates had to be substituted. These transfusions, in turn, caused a non-A, non-B hepatitis. In the further course of the illness, a Guillain-Barre polyneuropathy developed. Biopsy and electrophysiological tests excluded granulomatous involvement of the nerves as a cause of the latter. But it is likely that there was a pathogenetic connection between the hepatitis and the polyneuropathy. PMID- 2107070 TI - Comparison of persistence of seven bovine viruses on bovine embryos following in vitro exposure. AB - The ability of seven cytopathic strains of bovine viruses to adhere to the zona pellucida of six-to-eight day-old bovine embryos were compared. Embryos were exposed to virus by placing them either in virus suspensions or by culturing them on infected bovine turbinate cultures for 18-24 h. After exposure to bovine virus diarrhea virus (BVDV), infectious bovine rhinotracheitis virus (IBV), bluetongue virus (BTV), pseudorabies virus (PRV), vesicular stomatitis virus (VSV), parainfluenza 3 virus (PI3), or bovine enterovirus virus (BEV), the embryos were tested for virus by culture in bovine turbinate cells and by morphological examination using electron microscopy (EM). A special technique to minimize loss of embryos processed for EM was developed. More embryos had viral particles on the surface of the zona pellucida after exposure to 18-24 hour infected cell cultures than did embryos exposed to viral culture suspensions. The most dramatic finding was that BTV adhered in large numbers to the surface of the zona pellucida of exposed embryos. IBRV, PRV, and VSV comprised an intermediate group, with virions occasionally detected on the surface of exposed embryos after 5 washes. Therefore, extensive washing is required. The PI3 and BEV were easily removed from embryo-exposed virus by washing. BVD was difficult to identify morphologically, making assessment by EM unreliable. There was no evidence that any one of the seven viruses penetrated the intact zona pellucida. Using a micromanipulator, 42 embryos were also directly inoculated through the zona pellucida with +/- 50 picoliters of virus inoculum or medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107071 TI - Photochemical transformation in aqueous solution and possible environmental fate of ethylenediaminetetraacetic acid (EDTA). PMID- 2107072 TI - Effects of petroleum oils and their paraffinic, asphaltic, and aromatic fractions on photosynthesis and respiration of microalgae. AB - Inhibition of photosynthesis was more severe than that of respiration in Anabaena doliolum exposed to Assam crude oil, furnace oil, petrol, diesel, and kerosene. Variabilities in toxicity of these oils, which seem to be related to their aromatic and asphaltic contents, were observed. Diesel and furnace oil, due to greater concentrations of aromatics, were more toxic than other oils. The toxic effects of asphaltic fractions were similar to those of aromatics. The study showed that the effects of a particular fraction vary from oil to oil. Therefore, toxicity of an oil cannot be correctly predicted by mere estimation of its various fractions. Lower concentrations of Assam crude stimulated photosynthesis and respiration of blue-green algae (cyanobacteria); however, green algae did not show such a response. Stimulation was exerted only by paraffinic fractions of the test oils. PMID- 2107073 TI - Regulation of the yeast pheromone response pathway by G protein subunits. AB - The yeast GPA1, STE4, and STE18 genes encode proteins homologous to the respective alpha, beta and gamma subunits of the mammalian G protein complex which appears to mediate the response to mating pheromones. Overexpression of the STE4 protein by the galactose-inducible GAL1 promoter caused activation of the pheromone response pathway which resulted in cell-cycle arrest in late G1 phase and induction of the FUS1 gene expression, thereby suppressing the sterility of the receptor-less mutant delta ste2. Disruption of STE18, in turn, suppressed activation of the pheromone response induced by overexpression of STE4, suggesting that the STE18 product is required for the STE4 action. However, overexpression of both the STE4 and STE18 proteins did not generate a stronger pheromone response than overexpression of STE4 in the presence of wild-type levels of STE18. These results suggest that the beta subunit is the limiting component for the pheromone response and support the idea that beta and gamma subunits act as a positive regulator. Furthermore, overexpression of GPA1 prevented cell-cycle arrest but not FUS1 induction mediated by overexpression of STE4. This implies that the alpha subunit acts as a negative regulator presumably through interacting with beta and gamma subunits in the mating pheromone signaling pathway. PMID- 2107074 TI - Beta-lactam antibiotic biosynthetic genes have been conserved in clusters in prokaryotes and eukaryotes. AB - A cosmid clone containing closely linked beta-lactam antibiotic biosynthetic genes was isolated from a gene library of Flavobacterium sp. SC 12,154. The location within the cluster of the DNA thought to contain the gene for delta-(L alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), the first step in the beta-lactam antibiotic biosynthetic pathway, was identified by a novel method. This DNA facilitated the isolation, by cross-hybridization, of the corresponding DNA from Streptomyces clavuligerus ATCC 27064, Penicillium chrysogenum Oli13 and Aspergillus nidulans R153. Evidence was obtained which confirmed that the cross hybridizing sequences contained the ACVS gene. In each case the ACVS gene was found to be closely linked to other beta-lactam biosynthetic genes and constituted part of a gene cluster. PMID- 2107075 TI - Extinction of Ig genes expression in myeloma x fibroblast somatic cell hybrids is accompanied by repression of the oct-2 gene encoding a B-cell specific transcription factor. AB - In most instances, fusion of differentiated cell types with fibroblasts has resulted in the extinction of differentiation-specific traits of the nonfibroblast parental cell. To explore the genetic basis of this phenomenon, we have used a series of somatic cell hybrids between myeloma cells and fibroblasts. Previous findings show that in these hybrids expression of the immunoglobulin (Ig) genes was extinguished at the transcriptional level. Our present results show that NF-kappa B transcription factor, known to be critical for kappa-chain enhancer activity, is present although in a lower amount, in the nucleus and in the cytosolic fraction of most of these hybrids (probably attached to the previously postulated I-kappa B inhibitor). In contrast, the expression of the NF A2/OTF-2 transcription factor encoded by the oct-2 gene, which binds to the octameric motif located in the Ig promoters and heavy chain gene enhancer, is extinguished at the transcriptional level. Our data thus suggest that extinction of Ig genes expression occurs via an indirect mechanism in which a fibroblast factor suppresses transcription factor(s) which are critical for Ig transcription. PMID- 2107076 TI - Radiographic aspects in transcatheter contact dissolution of calcified gallbladder concrements. AB - The present study on 10 patients reports upon an attempt to perform percutaneous contact dissolution of partially calcified gallbladder concrements. These gallstones, which exhibited structural calcifications on CT scans, required time consuming complex dissolution procedures with transcatheter administration of methyl tert-butyl ether (MTBE) and ethylene diamine tetraacetic acid (EDTA). Insertion of the catheter system (5 F) was performed via a percutaneous transhepatic route. Catheter placement was maintained for a maximum of 4 days. Complete lysis was achieved in seven of the ten cases. In six patients, significant regional or disseminated chemically induced cholecystitis and pericholecystitis could be observed on CT examination. However, on follow-up CT examinations, these changes proved to be completely reversible. It has been demonstrated that tolerance of the gallbladder wall and adjacent tissue layer against the lytic media employed is rather limited and that meticulous controlling of the morphological reaction can be helpful in minimizing complications. PMID- 2107077 TI - Nitroglycerin has more favourable effects on left ventricular afterload than apparent from measurement of pressure in a peripheral artery. AB - Nitroglycerin (0.3 mg) was administered sublingually to 14 patients undergoing cardiac catheterization, and pressure waves compared in the ascending aorta and brachial artery. After nitroglycerin, ascending aortic systolic pressure fell in all cases (by 6-44, average 22 mmHg) whereas brachial systolic pressure remained unchanged (in three) or fell to a lesser degree (4-33, average 12 mmHg). Diastolic pressure did not change significantly. Alterations in pressure and in wave contour were explained on the basis of arterial dilation, with reduction in wave reflection. Nitroglycerin reduces left ventricular afterload through arterial dilation as well as preload through venous dilation. This effect on afterload is not apparent from measurement of pressure in the brachial artery. PMID- 2107078 TI - Flecainide acetate in atrial flutter and fibrillation. The arrhythmogenic effects. AB - The arrhythmogenic effects of flecainide in atrial fibrillation and flutter were assessed in a consecutive material of 100 patients without severe heart failure (NYHA class I or II). Severe arrhythmogenic events occurred in 9% (4-16%) of the patients: within the first 5 days of treatment in seven patients, and in two patients after 60 and 240 days of flecainide treatment. Patients with proarrhythmic events tended to be older and to have a longer QRS duration. Following flecainide therapy conversion to sinus rhythm was achieved in 21 of 43 patients (49%) with atrial fibrillation and in 10 of 29 (34%) with atrial flutter. It is concluded that flecainide, although an effective antiarrhythmic drug, has potential proarrhythmic effects and therefore cautious use of this drug is mandatory. PMID- 2107079 TI - Variable clinical presentation of carbonic anhydrase deficiency: evidence for heterogeneity? AB - The clinical and biochemical findings in an Italian sibship affected by carbonic anhydrase II deficiency are described. Evidence of clinical heterogeneity and an increased frequency of the disease in the Mediterranean area and the Middle East are discussed. PMID- 2107081 TI - Acute sodium valproate intoxication: occurrence of renal failure and treatment with haemoperfusion-haemodialysis. AB - In a child who probably received an overdose of sodium valproate, progressive coma, intermittent tonic-clonic seizures and anuria developed. Laboratory investigations revealed coagulopathy, and anaemia and mildly disturbed liver function. Progressive renal insufficiency, probably due to rhabdomyolysis and myoglobulinuria, occurred later. Treatment consisted of supportive measures, combined haemoperfusion and haemodialysis and IV thiopentone. Clinical and biochemical normalisation was observed after 11 days. PMID- 2107080 TI - Total parenteral nutrition associated cholestasis: a predisposing factor for sepsis in surgical neonates? AB - Of 496 neonates and infants less than 1 year of age admitted to the paediatric surgical intensive care unit (PSICU) over a 5 year period (1983-1987), 94 required total parenteral nutrition (TPN) for more than 14 consecutive days, generally due to congenital anomalies of the digestive tract. Cholestasis occurred in 15 of them and 12 of these patients developed sepsis. In contrast, of the 79 patients on TPN that remained free from cholestasis, only 23 developed sepsis. The mortality rate for the TPNAC-group was substantially higher than for the group without TPNAC. It is suggested that development of TPNAC might lead to impairment of non-specific cellular immunity in neonates. PMID- 2107082 TI - Nephrogenic adenoma in a patient with chronic renal failure associated with intravesical treatment with thiotepa. AB - We describe a patient with chronic renal failure and transitional cell carcinoma, in whom a nephrogenic adenoma of the bladder was diagnosed after a course of intravesical thiotepa treatment. PMID- 2107083 TI - Structure of rearranged and germ-line rabbit V kappa genes indicated that the CDR3 is encoded by the V kappa gene. AB - The third complementary-determining regions (CDR3) of rabbit kappa chains are unusually long and the length is more heterogeneous when compared to those of the mouse and the human kappa chains. To study how the rabbit kappa light (L) chain genes create diversity and generate CDR3, we analyzed the structure of a rearranged variable kappa gene (Vr) and the variable (Vg) and joining (Jg) regions of the putative precursor genes. Alignment of the Vr gene sequence with that of the Vg and Jg regions allowed precise determination of the recombination event. Five nucleotides between the recombination point and the J2 heptamer were deleted, indicating flexibility in the recombination producing rabbit kappa chains. The entire Vg is contained in the rearranged product demonstrating that neither a D element nor an N sequence addition are required for the CDR3 formation. Comparison of the Vr and the Vg gene sequences show base substitutions suggesting that somatic mutations may contribute to rabbit kappa L chain diversity. PMID- 2107084 TI - Structural characterization of human monoclonal cold agglutinins: evidence for a distinct primary sequence-defined VH4 idiotype. AB - Cold agglutinins that bind the developmentally regulated I red cell determinant occur naturally among human monoclonal IgM proteins. These autoantibodies are known to use light chains that derive mainly from the minor kappa III (kappa III) variable region subgroup. The kappa III subgroup is also highly expressed in monoclonal rheumatoid factors. However, while most monoclonal rheumatoid factors use structurally homologous heavy chains that derive from the VH1 family, information regarding the structure of the cold agglutinin heavy chains remains fragmentary. We demonstrate here that the kappa III cold agglutinin autoantibodies exclusively use heavy chains that derive from the VH4 family. Furthermore, these autoantibody heavy chains all express the same primary sequence-defined idiotype, corresponding to the second hypervariable region. These data indicate that cold agglutinins use a remarkably homogeneous subset of heavy chain variable regions. Moreover, unique patterns of preferential VH and VL pairing clearly distinguish the anti-I cold agglutinins from all other known monoreactive autoantibodies. PMID- 2107085 TI - Restricted utilization of VH and DH genes in leukemic rabbit B cells. AB - Polyclonal B cell leukemias have been generated in 17- to 20-day old Emu-myc transgenic rabbits. To analyze the repertoire of VH genes utilized in early B cells, eight VDJ genes were cloned from these leukemic cells. The nucleotide sequences of these genes indicated that seven of the eight VDJ genes encoded prototype VHa1, VHa2 or VHa3 allotypes. The two VDJ genes encoding VHa1 molecules had VH segments with identical nucleotide sequences; similarly, the VH segments of the four VDJ genes encoding VHa2 molecules were identical, with the exception of a single base pair. These data suggest that a limited repertoire of VH genes were utilized in the generation of these VDJ genes. The DH segments of these genes were limited to two DH families, D1 and D2, indicating that a restricted repertoire of DH genes also had been utilized. Since these leukemic cells probably developed early in ontogeny, we suggest that this restricted utilization of VH and DH genes is representative of B cells from developmentally immature rabbits. PMID- 2107086 TI - Effect of interferon-gamma and tumor necrosis factor-alpha on lymphoepithelial interactions within thymic nurse cells. AB - Isolated thymic nurse cells (TNC) represent a specialized microenvironment in vivo where thymocytes interact specifically with subcapsular epithelial cells. They are thought to play a critical role in the process of T cell differentiation. We demonstrate that recombinant murine interferon-gamma and recombinant human tumor necrosis factor-alpha can act on these interactions: they stimulate TNC-derived epithelial cells to establish interactions with thymocytes in vitro and to form new lymphoepithelial complexes. This phenomenon is partially inhibited by anti-Ia monoclonal antibodies. Implications of these findings for normal intrathymic differentiation are discussed. PMID- 2107087 TI - Regulation of Ig gene expression in normal lymphocytes. I. The half-life of secreted mu chain mRNA differs from that of membrane mu chain mRNA in resting and activated B cells. AB - Resting and activated B lymphocytes were used to study the stability of mu specific precursor and mature mRNA. Resting cells which predominantly process the mu precursor towards micron do so rather slowly as reflected in a precursor half life (T1/2) of 1-2 h. The small amount of secreted mu chain mRNA is fairly stable (T1/2 approximately 8 h) compared to membrane mu chain (T1/2 approximately 4 h). After activation the precursor processing is very fast (T1/2 approximately 10 min) and the stability of mu2, which now predominates, increases (T1/2 approximately 16 h) while the half-life of micron remains at about 4 h. The data indicate that normal B cells regulate mu-specific mRNA stability differently from tumor cells of the B cell lineage. PMID- 2107088 TI - Structural nature of the interaction between T lymphocyte surface molecule CD4 and the intracellular protein tyrosine kinase lck. AB - The strong non-covalent interactions between T lymphocyte surface CD4 or CD8 molecules and the intracellular membrane-associated protein tyrosine kinase lck are likely to mediate the role of CD4 and CD8 molecules in the immune response. The delineation of the structural nature of the CD4/lck and CD8/lck complexes is important for the understanding of the biochemical and functional significance of the interactions. Complementary charged regions in the C-terminal intracytoplasmic portions of CD4 or CD8, and in the N-terminal region of protein tyrosine kinase lck were noted. Peptides spanning these regions, residues 417 to 429 of CD4 and 10 to 22 of lck, were found to specifically dissociate these two molecules in CD4/lck complexes. A structural model of the interaction that accounts for its high stability is proposed. PMID- 2107089 TI - 3-((+-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and phencyclidine produce a deficit of passive avoidance retention in rats. AB - 3-((+-)-2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), phencyclidine (PCP) and diazepam were evaluated for their ability to produce a deficit for a single trial step-through passive avoidance response in rats. Pretraining administration with CPP at doses ranging from 2.0 to 10.0 mg/kg s.c. significantly decreased retention latencies 24 h after passive avoidance training. Similar effects were found with PCP at doses ranging from 0.5 to 1.7 mg/kg s.c. and diazepam at doses between 5.0-18.0 mg/kg s.c. Pretraining administration with the benzodiazepine antagonist, RO15-1788 at doses between 0.1 15 mg/kg s.c., did not alter retention latencies. Co-administration of RO15-1788 (0.01-15.0 mg/kg s.c.) with CPP (6.0 mg/kg s.c.) or PCP (1.0 mg/kg s.c.) failed to block decreases in latencies. However, when RO15-1788 was co-administered with diazepam (9.0 mg/kg s.c.) a dose-related antagonism of diazepam's effects were found. These results suggest that the behavioral actions of CPP and PCP on passive avoidance retention are not mediated via the benzodiazepine receptor complex. PMID- 2107090 TI - Endothelin and 5-hydroxytryptamine on rat pulmonary artery in pulmonary hypertension. AB - Contractile responses to endothelin, 5-hydroxytryptamine (5-HT), noradrenaline and potassium were obtained on isolated preparations of pulmonary artery from rats made pulmonary hypertensive by an injection of monocrotaline (105 mg/kg s.c.) 4 weeks previously. When compared with data obtained in control rats, the potencies (negative log EC50 values) for 5-HT, noradrenaline and potassium were increased (30, 3- and 3-fold, respectively), and the maximum contractions (mN/mm2) to endothelin, noradrenaline and potassium were reduced (65, 40 and 45% reduction). These changes were not seen 2 weeks after injection of monocrotaline, before pulmonary hypertension developed, or in preparations of aorta. It is concluded that monocrotaline-induced pulmonary hypertension affects pulmonary vascular responsiveness to spasmogens differentially. The comparative importance of endothelin and 5-HT as pulmonary vasoconstrictors may change in monocrotaline induced pulmonary hypertension, there being an increase in responsiveness to 5-HT and a decrease in responsiveness to endothelin. PMID- 2107091 TI - The effect of antidepressants on aversive periaqueductal gray stimulation in rats. AB - The selective serotonin (5-HT) uptake inhibitors fluvoxamine and sertraline had anti-aversive effects when administered acutely. Imipramine and clomipramine, which combine noradrenaline (NA) and 5-HT uptake blocking properties, did not have significant effects, whereas the mixed dopamine (DA)/NA uptake blocker nomifensine decreased the thresholds for escape from aversive periaqueductal gray stimulation. These results suggest that indirect 5-HT receptor activation suppresses periaqueductal gray aversion. Conversely, indirect DA and perhaps NA receptor activation appears to enhance periaqueductal gray aversion in rats. PMID- 2107092 TI - Evaluation of Ia expression in rat ocular tissues following inoculation with interferon-gamma. AB - It is becoming increasingly clear that IFN-gamma is a potent immunoregulatory protein which influences MHC class II (Ia) antigen expression and cellular functions of B cells, T cells, NK cells and macrophages. During the past 5 yr our laboratory has provided evidence that IFN-gamma modulates class II antigens on retinal cells (retinal pigment epithelial cells, endothelial cells) and is localized within the eye during human inflammatory conditions. In this study we evaluate the direct effect of IFN-gamma on ocular tissue. Lewis rats were inoculated intravitreally or under the retina with either recombinant IFN-gamma (20,000 U) or saline. At 2 hr, 1, 2 and 6 days postinoculation, the eyes were removed and frozen sections were evaluated by immunocytochemical staining with monoclonal anti-Ia antibodies and an irrelevant monoclonal anti-T cell antibody. Saline treated tissue and tissue removed 2 hr after IFN-gamma inoculation showed no significant staining for Ia antigens. However, eyes evaluated 24 hr after IFN gamma inoculation revealed Ia expression on a variety of ocular cells localized in the conjunctiva and anterior segment, such as conjunctival epithelium, keratocytes, iris epithelium, ciliary epithelium and choroidal cells. In the retina, retinal pigment epithelial (RPE) cells were Ia positive only when IFN gamma was injected directly under the retina. In conjunction with Ia expression, two striking changes were noted. An iritis was seen and infiltrating cells were detected in the inner retinal layers. Both of these phenomena have been observed in certain inflammatory eye diseases. These studies clearly substantiate the concept that IFN-gamma can regulate class II antigens in the eye and thus may perpetuate immune reactivity in this site. PMID- 2107093 TI - Role of monkey superior colliculus in saccade averaging. AB - We have investigated the involvement of collicular movement cells in the monkey in the execution of averaging saccades, elicited by a visual double-step stimulus. We found that, qualitatively, most (12/14) movement cells were recruited during averaging saccades in roughly the same way as for comparable visually-elicited saccades to single targets (V-saccades). However, movement-cell responses during averaging saccades in trials where the target suddenly changed direction were often less intense than for a comparable V-saccade. In these cases, the averaging responses were observed to be also slower than V-saccades of the same amplitude. Firing rate and double-step saccade dynamics were found to be significantly correlated in 9/14 cells tested. Several hypotheses for the collicular role in the generation of averaging saccades are discussed. PMID- 2107094 TI - Schistosoma japonicum: monoclonal antibodies to the Mr 26,000 schistosome glutathione S-transferase (Sj26) in an assay for circulating antigen in infected individuals. AB - Two monoclonal antibodies have been produced that bind to separate epitopes on the Mr 26,000 glutathione S-transferase (GST) of Schistosoma japonicum worms (Sj26). Both antibodies have been used in an enzyme immunoassay (EIA) with sera from infected individuals from the Philippines. Relatively high signals were obtained with sera from some, but not all, individuals who are positive for fecal eggs. Evidence was obtained that the material detected by the monoclonal antibodies was present in minute amounts and in some sera was bound in a complex with phosphorylcholine-containing molecules. It could not be absorbed by reaction with glutathione-agarose columns. There was no detectable immunoglobulin in the complex. The possibility exists that the complexes are composed of schistosome GST, or fragments, and damaged tegumental lipids shed as a result of surface immune attack. However, the presence of the native Sj26 molecule has not been proven. More detailed longitudinal studies in endemic areas are required to determine whether the assay can be used as an indicator of acquired resistance ("concomitant immunity") and whether it will be useful in the search for immunological correlates of this resistance in humans. PMID- 2107095 TI - Plasma thyroxine levels in Duchenne muscular dystrophy. AB - Some young Duchenne muscular dystrophy (DMD) patients (3-7 years) had total thyroxine (T4) levels and T4 to thyroxine binding globulin (TBG) ratios above the normal range and significantly increased free thyroxine indices (fT4I) which, however, remained within the normal range. Older DMD patients (7-11 years) had T4 and TBG levels and fT4I similar to normal. In both DMD groups the thyroxine binding index (TBI) values were in the normal range. PMID- 2107097 TI - The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum. AB - The relative importance of host and bacteria-derived deoxyribonucleic acid (DNA) in the increased viscoelasticity of purulent sputum in cystic fibrosis (CF) and other airway diseases is unclear. We report the identification of the DNA associated with mucus glycoproteins purified from the purulent sputum of 9 patients with CF. Mucus glycoproteins were purified from CF sputum by gel exclusion chromatography and the co-purifying DNA isolated by phenol extraction. Electrophoresis indicated that the DNA preparations had a size of approximately 300 to greater than 50,000 bases. The origin of the DNA was determined by slot blotting and subsequent hybridization with 32P-labelled DNA probes specific for human DNA sequences and those from bacterial species commonly isolated from CF sputum. The results indicated that in all cases the DNA was almost entirely human in origin. This implies that it is the patient's own DNA which may contribute to the rheological abnormalities of CF sputum. PMID- 2107096 TI - Organoselenides as potential immunostimulants and inducers of interferon gamma and other cytokines in human peripheral blood leukocytes. AB - A number of organoselenium compounds have been described as anti-inflammatory, antioxidant, glutathione peroxidase-like agents and inhibitors of prostaglandin synthesis. Here we report that bis [2-(N-phenyl-carboxamido)]phenyl diselenide, 2 phenyl-1,2-benzisoselenazol-3(2H)-one (Ebselen) and related compounds are inducers of interferon gamma (IFN-gamma) and tumor necrosis factor (TNF) in human peripheral blood leukocytes. The IFN and TNF response was rapid, occurring within 20 h, and high--up to 1000 and 2000 units ml-1--and was clearly related to the dosage and the structure of the compounds. The action of the compounds and phytohemagglutinin was synergistic. The IFN gamma and TNF production was reduced after removing adherent cells. Although the mode of action of the compounds is not known, they appear to interact directly or indirectly with both adherent and non-adherent leukocytes, and stimulate the synthesis of a set of different cytokines including factors controlling the cell proliferation. Therefore, organoselenides may be regarded as the biological response modifiers. PMID- 2107098 TI - Modulation of the affinity of aspartic proteases by the mutated residues in active site models. AB - The active sites of 3 types of aspartic proteases are modeled, based on crystallographic coordinates of endothiapepsin and of a model of HIV-1 protease. The enthalpies of deprotonation from neutral to mono-anion and to dianion are calculated with semiempirical minimal neglect of differential overlap, hydrogen bonding corrected (MNDO/H). This quantum mechanical study of models for the active sites of pepsins, human renin and retroviral aspartic proteases demonstrates that the replacements of Thr-218 from pepsins by Ala in human renin and of both Ser-35 and Thr-218 by alanines in retroviral proteases increases the proton affinity and modulates the charge distribution of those active sites compared to the pepsins. PMID- 2107099 TI - Granulosa cells as a source and target organ for tumor necrosis factor-alpha. AB - Tumor necrosis factor (TNF-alpha), a 17 kDa cytokine, is a product of activated macrophages which was recently shown to be produced by rat and bovine granulosa cells. In the present work, human granulosa cells derived from preovulatory follicles were used. It was demonstrated that human granulosa cells produce TNF alpha (5-10 units/300,000 cells per 15 h). This production was increased by addition of follicle-stimulating hormone or by a combination of human chorionic gonadotrophin and CSF to the culture media. TNF was also found in bovine follicular fluid and the concentration was higher in the periovulatory than mid cycle follicles. TNF-alpha was found to increase prostaglandin F-2 alpha production by human granulosa cells (P less than 0.001). We conclude that granulosa cells are both a source and target organ for TNF-alpha. PMID- 2107100 TI - The structural elements of hirudin which bind to the fibrinogen recognition site of thrombin are exclusively located within its acidic C-terminal tail. AB - Six lysyl residues of human thrombin (LysB21, LysB52, LysB65, LysB106, LysB107 and LysB154) have been previously shown to participate in the binding site of hirudin, a thrombin-specific inhibitor [(1989) J. Biol. Chem. 264, 7141-7146]. In this report, we attempted to delineate the region of hirudin which binds to these basic amino acids of thrombin. Using the N-terminal core domains (r-Hir1-43 and r Hir1-52) derived from recombinant hirudins and synthetic C-terminal peptides (Hir40-65 and Hir52-65)--all fragments form complexes with thrombin--we are able to demonstrate that the structural elements of hirudin which account for the shielding of these 6 lysyl residues are exclusively located within the acidic C terminal region. Since hirudin C-terminal peptides were shown to bind to a non catalytic site of thrombin and inhibit its interaction with fibrinogen [(1987) FEBS Lett. 211, 10-16], our data consequently imply that these 6 lysyl residues are constituents of the fibrinogen recognition site of thrombin. PMID- 2107101 TI - Cycle-related LHRH responsiveness of superfused pituitary cells in a Phenol red free medium. AB - Anterior pituitary cell cultures are frequently used in studying the control of gonadotropin secretion. Historically, many (if not most) of these studies have been performed in the presence of Phenol red as a pH indicator. Phenol red preparations, because of their potential estrogenic activity, may have influenced the results of previous studies defining the relative luteinizing hormone releasing hormone responsiveness of rat anterior pituitary-cells derived from various stages of the estrous cycle. We therefore felt it of interest to investigate this possibility by repeating our previous cycle-related superfusion studies [(1988) Life Sci. 42, 61-72] in the absence of these Phenol red preparations. Comparisons of data obtained in the presence or absence of Phenol red revealed cells derived from late proestrous (19.00) and cultured in the absence of Phenol red continued to evidence the highest LH responsiveness. However, diestrous 1 08.00 cells cultured in the absence of Phenol red were lower in responsiveness than previously observed in the presence of the substance and the responsiveness of proestrous 08.00 and 15.00 in the presence was lower in comparison to the same stages in the absence of Phenol red. The results suggest that Phenol red preparations are capable of modulating LHRH responsiveness in superfusion and that the effect is more pronounced at certain cycle stages than at others. PMID- 2107102 TI - De novo protein synthesis is essential to human interferon gamma gene expression by the stimulation with polyI:polyC. AB - Transcription of human interferon (IFN) gamma gene is induced in human peripheral lymphocyte nylon-nonadherent cells (NNA cells) by double strand RNA poly I:poly C [(1985) J. Interferon Res. 5, 77-84]. In this report, the necessity of de novo protein synthesis in an early stage of IFN gamma gene expression is described. For induction of IFN gamma gene expression, only initial 4 h treatment of poly I:poly C to NNA cells is sufficient. Addition of inhibitor of protein synthesis, cycloheximide (CHX), at an early stage of induction periods (0-4 h) inhibits the IFN gamma induction by poly I:poly C. Cell free translation assay using RNAs isolated from NNA cells which are induced by poly I:poly C in the presence of CHX reveals that in these RNAs, IFN gamma mRNA does not exist. These results demonstrate that CHX inhibits de novo synthesis of a certain protein (or proteins) and for lack of the protein(s), IFN gamma mRNA cannot be transcribed. The evidence is also described in this report which suggests that the essential protein(s) might be that (those) involved in protein kinase C (pkC) activation. PMID- 2107103 TI - Identification in human erythrocytes of mono(ADP-ribosyl) protein hydrolase that cleaves a mono(ADP-ribosyl) Gi linkage. AB - A novel enzymatic activity, the hydrolysis of linkages between mono(ADP-ribose) and cysteine residues in Gi prepared by eukaryotic ADP-ribosyltransferase C [(1988) J. Biol. Chem. 263, 5485-5489] was found in the cytosol of human erythrocytes. The mono(ADP-ribosyl) Gi hydrolase, tentatively named ADP-ribosyl protein hydrolase C was partially purified by sequential chromatographies on DEAE cellulose and Blue Sepharose. This enzyme catalyzes the release of ADP-ribose from mono(ADP-ribosyl) Gi. Its activity was enhanced by Ca2+ and inhibited by ADP ribose. The presence of this enzyme in eukaryotic cells suggests that endogenous mono(ADP-ribosyl)ation of Gi is a reversible post-translational modification. PMID- 2107104 TI - Thrombospondin binding by keratinocytes: modulation under conditions which alter thrombospondin biosynthesis. AB - Our recent studies have shown that thrombospondin (TSP) is a potent adhesion factor for normal human keratinocytes. Stimulation of adhesion is presumed to result from the binding of TSP to high-affinity receptors on the surface of responsive cells. The present study indicates that keratinocytes bind TSP in a receptor-like manner. Binding is time- and concentration-dependent, saturable, reversible and specific. Approximately 180 ng of TSP can be bound per 1 x 10(5) cells at saturation and half-maximal binding occurs at 22 nM. A series of monoclonal antibodies to various regions of the TSP molecule were examined for effects on TSP binding and TSP-induced adhesion. An antibody directed against the heparian-binding domain of the TSP molecule significantly inhibited TSP binding but had no effect on adhesion. In contrast, three antibodies which recognize epitopes in the 140-kDa fragment of the molecule inhibited both binding and adhesion. In a previous study we showed that treatment of keratinocytes with interferon-gamma inhibited TSP production and inhibited adhesion under unstimulated conditions as well as in response to TSP. The present study shows that interferon-gamma also inhibits TSP binding by keratinocytes. When the data from the present study are taken together with our past data, they suggest that normal human keratinocytes have the capacity to bind TSP and use this capacity to bind endogenously synthesized TSP. This provides a mechanism for utilizing the endogenously produced TSP to stimulate adhesion. PMID- 2107105 TI - Prostacyclin versus thromboxane metabolite excretion: changes in pregnancy and labor. AB - Urinary TXB2 and 6-keto-PGF1 alpha were measured by high pressure liquid chromatography combined with radioimmunoassay, in order to determine whether or not urinary excretion of 6-keto-PGF1 alpha and TXB2 followed a same pattern in pregnancy and labor. The excretion of 6-keto-PGF1 alpha was higher than that of TXB2 in both non-pregnant and pregnant women, but the ratio between them increased in pregnancy. The urinary excretion of both 6-keto-PGF1 alpha and TXB2 excretion was significantly increased (p less than 0.001) in pregnancy. Labor was associated with a much wider inter-individual variation in the excretion of 6 keto-PGF1 alpha and TXB2 than observed in pregnancy and in non-pregnant women. Also, the ratio between the two compounds varied more in labor than in pregnancy. The data indicate that the urinary levels of these two compounds do not follow a single well-determined pattern in pregnancy and labor. PMID- 2107106 TI - Postmenopausal androgen secreting ovarian tumour: pathophysiological implications; a case report. AB - Hyperandrogenism in women is usually accompanied by a disruption of the hypothalamic-pituitary-ovarian axis; however, the precise effect of chronically elevated androgens on this axis is poorly understood. We report a postmenopausal woman with a virilizing ovarian tumour in whom the effects of chronic testosterone secretion on the hypothalamic-pituitary axis was investigated. A 56 year-old woman was evaluated for hirsutism and hyperandrogenism of recent onset. Peripheral serum testosterone was high (19.4 nmol/l), while gonadotropins were below normal for a postmenopausal woman, FSH (19.7 IU/l) being higher than LH (10.3 IU/l). Four LH and 1 FSH pulse were detected over 4 h. A left intraovarian testosterone secreting tumour, shown by catheterization of the ovarian veins and containing imperfect crystalloids of Reinke, was excised. Postoperatively, peripheral testosterone became undetectable, while gonadotropins rose to normal postmenopausal values. This patient's LH/FSH ratio was less than 1, in contrast with other situations of chronic hyperandrogenism. This could be explained by the concomitant hypoestrogenic state, and/or the theoretical absence of inhibin. The interest of this case resides in that it constitutes an appropriate model for studying the effects of testosterone on LH and FSH secretion in the absence of the other two classically involved modulators, namely oestrogens and inhibin. PMID- 2107108 TI - An epidemiological study on increased length of stay. AB - The epidemiologic triad of causation states that all illness results from a disequilibrium between host, agent and environmental factors. The "illness" investigated in this report--increased LOS--resulted from a combination of: patient factors--the increased prevalence of chronic diseases in childhood, a revolution in neonatal survival and an increase in survivorship in general for severe diseases, such as congenital anomalies and genetic diseases; agent factors -the transition from agents of infectious disease to agents of chronic disease as well as iatrogenesis; and health care environmental factors--equity issues involving the ethics of treatment, changes in medical technology and patterns of medical practice. The use of preadmission testing, increased participation by parents in the care of their children, an investigation of the appropriate venue for care of chronically ill children and the back transfer of recovering children to their home hospitals were recommended and considered by the hospital's administration and board of governors. PMID- 2107107 TI - Synergistic effect of glucocorticoids and androgens on the hormonal induction of tissue plasminogen activator activity and messenger ribonucleic acid levels in granulosa cells. AB - Tissue-type plasminogen activator (tPA) is secreted by rat granulosa cells in response to treatment with activators of protein kinase A (follitropin, FSH), protein kinase C (gonadotropin-releasing hormone, GnRH) and tyrosine kinase (epidermal growth factor, EGF). Because steroid hormones have been shown to enhance the gonadotropin stimulation of ovarian differentiation, we investigated the effects of steroid hormones, alone or together with various kinase activators, on tPA activities and mRNA levels in cultured rat granulosa cells. Treatment of cells with dexamethasone (DEX; a glucocorticoid agonist) or R1881 (an androgen agonist) caused an increase in tPA secretion and mRNA levels. In addition, the stimulation of tPA activity and mRNA levels by FSH (50 ng/ml) was synergistically enhanced by cotreatment with DEX or R1881 in a time-dependent manner with 2.8- and 1.6-fold increase at 9 h after incubation as compared to cells treated with FSH alone. In contrast, treatment with diethylstilbestrol had no effect on tPA levels. Furthermore, tPA activity and mRNA levels induced by GnRH and EGF were also increased by cotreatment with DEX or R1881 as compared with cells treated with GnRH or EGF alone. Likewise, the stimulation of tPA mRNA levels by dibutyryl cAMP, a protein kinase A activator, and phorbol myristate acetate (PMA), a protein kinase C activator, was enhanced by cotreatment with DEX or R1881. These results demonstrate that glucocorticoid and androgen enhance tPA secretion and mRNA levels stimulated by FSH, GnRH and EGF in granulosa cells. The rat granulosa cells provide a useful model for studying the mechanism of regulation of tPA gene expression by steroid hormones. PMID- 2107109 TI - [From non-A non-B hepatitis to hepatitis C virus]. PMID- 2107110 TI - [Hepatitis C virus: a discovery of molecular biology]. PMID- 2107111 TI - Revolutionary lifesaving therapy for acute hepatic failure, or yet another false hope? PMID- 2107112 TI - Flexible sigmoidoscopy plus air contrast barium enema versus colonoscopy for suspected lower gastrointestinal bleeding. AB - A randomized, controlled trial was performed to compare the diagnostic yields and cost-effectiveness of two strategies for the evaluation of nonemergent lower gastrointestinal bleeding. Three hundred eighty patients aged greater than or equal to 40 yr were randomized to undergo initial flexible sigmoidoscopy plus air contrast barium enema or colonoscopy; 332 completed the initial studies. Initial colonoscopy detected more cases of polyps less than 9 mm in size, adenomas, and arteriovenous malformations but fewer cases of diverticulosis. No significant difference was found between strategies in the number of patients detected with cancers or polyps greater than or equal to 9 mm in size. In both strategies, cancers were more common in subjects aged greater than or equal to 55 yr (8% overall) than in those aged less than 55 yr (1%). Among patients aged less than 55 yr with suspected lower gastrointestinal bleeding, initial flexible sigmoidoscopy plus air contrast barium enema is a more cost-effective strategy for the detection of colonic neoplasms than initial colonoscopy. However, initial colonoscopy is more cost effective for those aged greater than or equal to 55 yr. PMID- 2107113 TI - Additive effects of ileal secretagogues in the rat. AB - Although clinical diarrhea is often caused by more than one enteropathogen, it is not known whether secretagogues have additive effects on secretion. This question was examined in anesthetized, ventilated rats by exposing the ileum to secretory agents with different mechanisms of action. Four hours after inoculation of ileal loops with either cholera toxin or saline, transport was measured during perfusion with Ringer's solution, with Ringer's solution containing Escherichia coli heat-stable enterotoxin or mannitol, or with Ringer's solution containing both heat-stable enterotoxin and mannitol. We found that heat-stable enterotoxin caused similar decrements in water absorption in loops exposed to Ringer's solution, hypertonic mannitol, cholera toxin, and cholera toxin plus mannitol. By contrast, the decrement in water transport caused by hypertonic mannitol was inversely related to the level of ongoing water transport. In addition, the electrolyte transport changes caused by each enterotoxin were preserved despite the presence of other secretory agents. These data suggest that the transport effects of secretagogues with different mechanisms of action are additive in the ileum. However, the absolute decrements in water absorption may be independent of (heat-stable enterotoxin and cholera toxin) or dependent on (hypertonic mannitol) the ongoing level of water transport. PMID- 2107114 TI - Oral prostaglandin E analogues induce intestinal migrating motor complexes after a meal in dogs. Evidence for a central mechanism. AB - The effects of oral, intravenous, and intracerebroventricular administration of synthetic derivatives of prostaglandins E1 (misoprostol) and E2 (enprostil) on postprandial gastrointestinal motility were investigated in dogs chronically fitted with strain gauge transducers on the antrum and the proximal and middle jejunum. Synthetic prostaglandin E analogues administered orally at a dose of 20 50 micrograms/kg 15 min before the meal did not modify the postprandial pattern of gastric contractions but suppressed the spontaneous postprandial irregular activity on the jejunum and induced a cyclic pattern of migrating motor complexes for 4-6 h after the meal. These postprandial migrating motor complexes induced by prostaglandin E were propagated between the two recording sites and had a period similar to that observed in the fasted state. However, the duration of phase 2 was significantly increased and the amplitude of the phase 3 decreased. This jejunal cyclic motor pattern was reproduced by administration of synthetic prostaglandin E derivatives either intravenously (4-10 micrograms/kg) 15 min before the meal or intracerebroventricularly (50 ng/kg) 1 h after the meal. The intestinal migrating motor complex activity observed after oral administration of synthetic prostaglandin E derivatives was abolished by the previous intracerebroventricular (40 micrograms/kg) but not intravenous (200 micrograms/kg) administration of SC-19220, a receptor antagonist of prostaglandin E. These results suggest that oral administration of synthetic prostaglandin E1 (misoprostol) or prostaglandin E2 (enprostil) analogues before a meal induces postprandial migrating motor complexes on the jejunum in dogs through a mechanism involving central prostaglandin receptors. PMID- 2107115 TI - Divalent hapten-induced intestinal anaphylaxis in the mouse enhances macromolecular uptake from the stomach. AB - The capacity of the stomach to participate in anaphylaxis induced by the hapten N,N'-di-2,4,dinitrophenyllysine (di-DNP-lysine) was examined in BDF1 female mice immunized with dinitrophenylated Ascaris suum extract. Immunized animals underwent laparotomy and nontraumatic pyloric occlusion using a microvascular clamp. Following wound closure, animals were gavage-fed ovalbumin together with di-DNP-lysine. Other mice were subjected to systemic anaphylaxis by intravenous injection of di-DNP-lysine administered 1 min after gavage feeding of ovalbumin. The intravenous and intragastric administration of di-DNP-lysine led to a sixfold or greater increase in serum immunoreactive ovalbumin. Examination of 1-micron sections of gastric tissue from DNP-Asc-immunized and unimmunized mice showed an intact mucosal and submucosal architecture. A 75% increase in the number of mast cells below the muscularis mucosa was seen in immunized compared with unimmunized BDF1 mice. Gastric tissue sections from immunized mice challenged orally or intravenously with di-DNP-lysine showed compaction of erythrocytes in blood vessels, degranulation of mast cells, degenerative changes in the gastric epithelium, expulsion of mucus from gastric glands, and edema in the lamina propria. The present model may be useful for further defining the consequences of anaphylaxis on the development of immune responses to dietary antigens. PMID- 2107116 TI - Endoscopic versus operative gastrostomy: final results of a prospective randomized trial. AB - This study compared operative gastrostomy (OG) (by surgeons) with endoscopic gastrostomy (PEG) (by physicians) in a prospective randomized fashion to determine whether one technique was superior. PEG (Sachs-Vine) and OG (Stamm) were done using local anesthesia. Patients were assessed for complications, mortality, tube function, and cost. Groups were equally matched for indications and underlying disease. Fifty-seven had OG and 64 had attempted PEG. Complications occurred in 26% of OG patients and 9% died. Complications occurred in 25% of PEG patients and 12% died. Tube feeding was initiated in both groups within a mean of 29 (24 to 72) hours of the gastrostomy placement. OG cost $1675 and PEG $979 to perform. Twenty-one PEG patients required endoscopic tube change which raised their total cost to $1574. We conclude there is no difference between OG (using local anesthesia) and PEG with regard to morbidity, mortality, or tube function. The endoscopic technique does appear to have economic advantage. PMID- 2107117 TI - Combination of midazolam and flumazenil in upper gastrointestinal endoscopy, a doubleblind randomized study. AB - We evaluated the clinical usefulness of flumazenil (formerly Ro15-1788), a benzodiazepine antagonist, in combination with midazolam in upper gastrointestinal endoscopy. Thirty outpatients were randomized into two groups: those receiving flumazenil and those receiving placebo after endoscopy. For sedation, only midazolam was used. Performances pre-sedation and post-sedation (at 30 and 60 min) were analyzed using the Trieger test, Number Connection test, and Digit Symbol test. Patients receiving flumazenil were fully alert and able to ambulate 5 min after injection with this medication. Performances at 30 min in the Trieger, Number Connection, and Digit Symbol tests were significantly better in the group receiving flumazenil, p less than 0.005, p less than 0.025, and p less than 0.01, respectively. No phlebitis, nausea, vomiting, or anxiety were noted. No resedation events were documented. We conclude that flumazenil can dramatically shorten the recovery period following sedation with midazolam in upper gastrointestinal endoscopy, and its use is not associated with major side effects. PMID- 2107118 TI - Small intestinal perforation following replacement of a percutaneous endoscopic gastrostomy tube. PMID- 2107119 TI - Utilization of a silicone gastrostomy feeding port in the gallbladder. PMID- 2107120 TI - [FSH-producing hypophyseal tumor in a 13-year-old girl]. AB - We report on a 13 year old girl with a FSH, secreting pituitary tumour, who was presented with recurrent bleeding disorders. Gynaecological examination revealed large cystic ovarian tumours on both sides. The endocrinological work-up showed high serum levels of oestradiol and FSH, and low serum levels of testosterone and LH. Computed tomography demonstrated a pituitary tumour of 3 cm diameter. PMID- 2107121 TI - Identification of cis-regulatory elements required for larval expression of the Drosophila melanogaster alcohol dehydrogenase gene. AB - The Alcohol dehydrogenase (Adh) genes of two distantly related species, Drosophila melanogaster and Drosophila mulleri, display similar, but not identical, patterns of tissue-specific expression in larvae and adults. The regulatory DNA sequences necessary for wild-type Adh expression in D. mulleri larvae were previously reported. In this paper we present an analysis of the DNA sequences necessary for wild-type Adh expression in D. melanogaster larvae. We show that transcription from the proximal promoter of the melanogaster Adh gene is regulated by a far upstream enhancer and two or more elements near the transcription start site. The enhancer is tissue specific and stimulates transcription to high levels in fat body and to lower levels in midgut and malpighian tubules whether linked to the proximal promoter or to a heterologous promoter. The enhancer activity localized to at least two discrete regions dispersed over more than 1.7 kb of DNA. Deletion of any one of these subregions reduces Adh transcription in all three larval tissues. Similarly, two regions immediately upstream of the proximal promoter start site are necessary for wild type transcription levels in all three tissues. Thus, each of the identified regulatory elements is sufficient for low levels of Adh gene expression in all three larval tissues, but maximal levels of expression requires the entire set. PMID- 2107122 TI - Analysis of autosomal dosage compensation involving the alcohol dehydrogenase locus in Drosophila melanogaster. AB - An example of autosomal dosage compensation involving the expression of the alcohol dehydrogenase (Adh) locus is described. Flies trisomic for a quarter of the length of the left arm of chromosome two, including Adh, have diploid levels of enzyme activity and alcohol dehydrogenase messenger RNA. Subdivision of the compensating trisomic into smaller ones revealed a region that exerts an inverse regulatory effect on alcohol dehydrogenase activity and messenger RNA levels and a smaller region surrounding the structural gene that exhibits a direct gene dosage response. The two opposing effects are of sufficient magnitude that they cancel when simultaneously present resulting in the observed compensation in the larger aneuploid. An Adh promoter-white structural gene fusion construct is affected by the inverse regulatory region indicating that the effect is mediated through the Adh promoter sequences. The role of autosomal dosage compensation in understanding aneuploid syndromes and karyotype evolution in Drosophila species is discussed. PMID- 2107123 TI - Comparison of proC and other housekeeping genes of Pseudomonas aeruginosa with their counterparts in Escherichia coli. AB - In a comparative study of housekeeping genes of Pseudomonas aeruginosa and Escherichia coli, the nucleotide sequence of a proline biosynthetic gene, proC, of P. aeruginosa has been determined. The subunit molecular mass (approximately 29 kDa) and the N-terminal amino acid sequence of purified delta 1-pyrroline 5 carboxylate reductase, the proC gene product, were in agreement with the proC nucleotide sequence. A survey of pairs of isofunctional genes from P. aeruginosa and E. coli reveals that within each pair, translated genes (including proC) have diverged more strongly than have untranslated genes specifying ribosomal or transfer RNAs. The translated genes, but not the untranslated ones, have a G + C content that is typical of the respective genomic G + C contents. PMID- 2107124 TI - The melanin operon of Streptomyces antibioticus: expression and use as a marker in gram-negative bacteria. AB - The melC operon of Streptomyces antibioticus contains two genes, melC1 and melC2, necessary for the production of melanin pigment. We transferred the coding sequence of melC1 and melC2 to Escherichia coli plasmid pMTL23 such that its transcription was under the control of the lac promoter and melC1 was translationally fused to the lacZ alpha fragment. E. coli cultures containing this plasmid, pIF413, produced melanin after overnight incubation on 2YT agar supplemented with 0.1 mM CuCl2, 0.36 mM IPTG (or 0.2% lactose), and 2 mM tyrosine. Erwina carotovora could also be transformed by pIF413 to produce melanin. Two shuttle vectors were constructed: pLUS415 for E. coli and Streptomyces, and pLAF413 for E. coli and Xanthomonas campestris. These vectors confer melanin pigmentation in all the hosts that harbor them. The melC sequence provides the vectors with a convenient cloning marker for insertional or replacement inactivation. PMID- 2107125 TI - Development of a beta-galactosidase alpha-complementation system for molecular cloning in Bacillus subtilis. AB - A versatile beta-galactosidase alpha-complementation system for Bacillus subtilis was developed, which can be used for molecular cloning in this Gram+ organism. The cloning system, which is based on the highly efficient host-vector system 6GM pHP13, offers several advantages over previously described systems: (1) convenient direct selection of recombinants; (2) the cloning of large heterologous DNA fragments with high efficiency; and (3) the availability of six unique target sites: SphI, NdeI, NheI, BamHI, SmaI and EcoRI. PMID- 2107126 TI - Comparative expression of the pC194 cat gene in Streptococcus pneumoniae, Bacillus subtilis and Escherichia coli. AB - The expression of the cat gene of the staphylococcal plasmid pC194 present in the pLS1-pC194 composite plasmid pJS37 was lower in Streptococcus pneumoniae and Escherichia coli than in Bacillus subtilis. Different transcription start points (and, by inference, different promoter utilization) of the cat mRNA synthesized in S. pneumoniae or B. subtilis were detected. Plasmid pJS37 is prone to deletion formation when host cells are grown in the presence of chloramphenicol (Cm). The analysis of the expression of the cat gene carried by the deleted derivatives of pJS37 has shown that a new promoter for the synthesis of cat mRNA is involved in the selective advantage conferred to the host by those deleted plasmids. Characterization of either in vivo or in vitro deleted plasmids has shown that the nucleotide sequence that could encode for a putative leader peptide is required for the Cm-induced pC194 cat gene expression. PMID- 2107127 TI - Cloning and expression of draTG genes from Azospirillum lipoferum. AB - A genomic library of Azospirillum lipoferum was constructed with phage lambda EMBL4 as vector. From this library, the genes encoding dinitrogenase reductase ADP-ribosyltransferase (DRAT), draT, and dinitrogenase reductase-activating glycohydrolase (DRAG), draG, were cloned by hybridization with the heterologous probes of Rhodospirillum rubrum. As in R. rubrum, draT is located between draG and nifH, the gene encoding dinitrogenase reductase (a substrate for the DRAG/DRAT system). In the crude extract of Escherichia coli harboring the expression vector for this region, DRAT and DRAG enzyme activities were detected, confirming the identity of the cloned genes. Southern hybridization with genomic DNA from different Azospirillum spp., demonstrated a correlation between observable draTG hybridization and the biochemical demonstration of this covalent modification system. PMID- 2107128 TI - HLA DR and DQ expression on human retinal pigment epithelial cells in vitro. AB - In a previous immunohistopathological study, we demonstrated a deviant expression of class II antigens on the uveal pigment epithelial cells of patients with proliferative diabetic retinopathy. The mechanisms triggering this abnormal expression by epithelial cells are not well known, and we tried to induce this phenomenon on primary cultures of human retinal pigment epithelial (RPE) cells. Confluent RPE-cell monolayers were supplemented with several biological or chemical reagents [recombinant interferon gamma, phytohemagglutinin A-P (PHA-P), phorbol-myristate acetate (PMA), recombinant interleukin-2, fibroblast growth factor (FGF), Insulin], to investigate their ability to induce HLA DR and DQ expression. On days 1, 3 and 5 after stimulation, the cells were incubated with monoclonal antibodies directed against human class II antigens: all reagents used failed to induce class II antigen: all reagents used failed to induce class II antigen expression. However, on day 7, we demonstrated the presence of numerous positive HLA DR and HLA DQ cells stimulated by gamma interferon, the percentages being closely related to the dose of this lymphokine. These findings, together with those of other investigators and our previous work on uveal pigmented epithelial cells in diabetic patients, may shed light on the exact implication of RPE in many poorly documented ocular diseases. PMID- 2107129 TI - The fallacy of impoverishment. AB - Several recent studies have challenged the assumption that Medicaid requires impoverishment. Although two-thirds of the elderly poor are not covered by Medicaid, many nursing home Medicaid recipients retain sizeable assets, which pass to their heirs without repayment of public costs. The magnitude of asset spenddown is much smaller than previously believed. This article discusses these findings and explores their significance to the long-term care financing crisis. PMID- 2107130 TI - Toward a knowledge base for long-term care finance. PMID- 2107131 TI - Medicaid spenddown in nursing homes. AB - This paper employs information from nationally representative surveys to examine the incidence and causes of Medicaid spenddown among disabled elderly persons. About 10% of nursing home discharges experience "asset spenddown," the process of converting from private pay to Medicaid. In contrast, over 50% of nursing home patients remain private pay throughout their stays. In addition, becoming a Medicaid patient is more common among community residents than among nursing home residents. Implications of findings for health care policies are discussed. PMID- 2107132 TI - Acetate absorption in the normal and secreting rat jejunum. AB - Acetate absorption was studied in rat jejunum using steady state perfusion in vivo. Absorption conformed to apparent saturation kinetics and was similar in magnitude to glucose absorption. When compared with normal saline, acetate perfusion was associated with luminal alkalinisation. There was no difference in total CO2 secretion when similar rates of acetate and glucose absorption were compared, suggesting that total CO2 secretion was the result of mucosal metabolism. Absorption of acetate and propionate were mutually inhibitory. Acetate absorption was also inhibited by Tris-Hepes pH 7.0. When the gut was pretreated with cholera toxin to induce a secretory state, acetate absorption was reduced by 41.9%. This effect could be reproduced if similar water secretion was osmotically induced by the addition of mannitol. These data suggest that acetate is absorbed, at least, partially by non-ionic diffusion in the rat jejunum and that its absorption is reduced in the secreting intestine by solvent drag. PMID- 2107134 TI - [Blood culture for diagnosing juvenile chronic myeloid leukemia; relationship to neurofibromatosis]. AB - During the past 12 years we studied children with unexplained chronic leukocytosis and other findings suggestive of acute or chronic myeloid leukemia (AML; CML). We used cultures in soft agar of peripheral blood for granulocyte macrophage colony-forming cell (GM-CFC) analysis. Colonies were counted, examined morphologically and cytochemically and the findings in patients were compared with those in normal children and patients with leukemoid reactions. 2 children with confirmed CML and neurofibromatosis (NF) were similarly evaluated. Additional studies in 1 of them and in his mother who had NF, included establishment of fibroblast and blood cultures from affected skin and tumor, and stimulation of normal bone marrow-derived GM-CFC by these fibroblasts and the conditioned medium (CM) from these cultures. Growth of GM-CFC from blood cultures of CML and AML patients was significantly enhanced in comparison with blood cultures from normal donors, or patients with other myeloproliferative disorders or leukemoid reactions. Enhanced GM-CFC growth-supportive activity was obtained from CML-NF skin and tumor culture CM in comparison with CM from normal fibroblasts. These results indicate the diagnostic value of blood culture GM-CFC in juvenile CML, and its usefulness in differentiating between CML and other disorders involving leukocytosis. They suggest a possible connection between NF foci and the enhanced proliferation of blood GM-CFC in CML. PMID- 2107133 TI - 13CO2 breath test to measure the hydrolysis of various starch formulations in healthy subjects. AB - 13CO2 starch breath test was used to study the effect of physicochemical characteristics of starch digestion. As starch is hydrolysed to glucose, which is subsequently oxidised to CO2, differences in 13CO2 excretion after ingestion of different starch products must be caused by differences in hydrolysis rate. To study the effect of the degree of chain branching, waxy starch, containing 98% amylopectin, was compared with high amylose starch, containing 30% amylopectin, and normal crystalline starch, containing 74% amylopectin. The effect of the extent of gelatinisation was studied by comparing extruded starch and crystalline starch. Finally, the possible inhibitory effect of adding wheat fibre to extruded starch on the hydrolysis rate was studied. The 13CO2 excretion from two to four hours after intake of crystalline starch was significantly lower than that of extruded starch. Waxy starch was hydrolysed much faster than high amylose starch, but there was no significant difference between waxy starch and normal crystalline starch. Addition of wheat fibre did not influence the hydrolysis rate. The 13CO2 starch breath test is an attractive test for the study of factors affecting carbohydrate assimilation. PMID- 2107135 TI - Pharmacology of pepsinogen secretion: influence of pentagastrin on pepsinogen secretion in man. AB - To investigate the effect of pentagastrin on serum and urinary pepsinogens and gastric pepsin, eight healthy male volunteers were studied twice during continuous intragastric perfusion with either NaCl 0.9% or 0.1 M HCl in random order. To the perfusate 3 mg/ml phenol red was added as inert recovery marker. Gastric content was aspirated in 15-minute samples, 4 basally and subsequently 6 during continuous i.v. infusion of pentagastrin 1.5 micrograms/kg/h. Furthermore, serum and urine samples were collected immediately before and after each test. Gastric pepsin output increased after pentagastrin. There were no differences in basal or stimulated pepsin output during saline or HCl perfusion despite marked differences in intra-gastric acidity and acid delivery to the duodenum. In addition, no significant changes in serum pepsinogen levels or urinary pepsinogen excretion were observed after pentagastrin infusion. It is concluded that pentagastrin stimulates gastric pepsin secretion directly, but does not stimulate the release of pepsinogens into the systemic circulation. PMID- 2107136 TI - Nutritional care for patients with Crohn's disease. AB - Protein calorie malnutrition, in addition to deficits of other nutrients, occurs frequently among patients with Crohn's disease. In most instances the mechanisms by which these deficits occur are multifactorial. The most appropriate method to assess nutritional status includes a nutritionally oriented medical history and physical examination combined with a measurement of serum albumin. If the gut can be used safely, enteral nutrition is the preferred feeding method for Crohn's disease patients needing nutritional support. The advantages of enteral nutrition are stimulatory effects on gastrointestinal structure and function and reduced cost when compared to parenteral feeding. If the gastrointestinal tract cannot be used safely, parenteral nutrition is recommended. The presence of Crohn's disease among prepubertal children produces serious growth failure which can be reduced or arrested by appropriate nutritional interventions. Significant numbers of Crohn's disease patients ar now receiving both enteral and parenteral nutrition in the home setting. PMID- 2107137 TI - Energy metabolism in patients with acute and chronic liver disease. AB - Energy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsy-proven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 +/- 4.0 (mean +/- S.E.M.), 216.4 +/- 4.7 and 228.8 +/- 7.1 (p less than 0.05 vs. controls), respectively. When related to body surface area (kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 +/- 0.02), patients with acute hepatitis (1.03 +/- 0.02) and cirrhotic patients (1.06 +/- 0.03). However, when related to 24-hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was increased in cirrhosis (p less than 0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% +/- 5%), carbohydrate (2% +/- 4%) and protein (12% +/- 1%) were different from those of normal controls who metabolized 45% +/- 4%, 38% +/- 4%, 17% +/- 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate. In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrhosis resembles that in starvation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107138 TI - Synaptophysin: a sensitive and specific marker for ganglion cells in central nervous system neoplasms. AB - Synaptophysin, a 38-kilodalton glycoprotein found in synaptic vesicle membranes, has been shown to be a sensitive marker of neuroendocrine differentiation in non central nervous system (CNS) tumors. We analyzed the patterns of synaptophysin immunoreactivity in CNS neoplasms in comparison with various normal CNS sites in biopsies. Normal gray matter structures all showed a diffuse punctate granular pattern of neuropil staining without staining of neuronal cell bodies. In contrast, neoplastic ganglion cells in 18 of 18 gangliogliomas/gangliocytomas showed intense immunoreactivity outlining the borders of the cell bodies. Focal staining was also seen in five of 16 primitive neuroectodermal tumors and in one of three central neurocytomas, but these tumors had a finely granular neuropil pattern of immunoreactivity more like that of normal gray matter than like that of the gangliogliomas. All 35 examples of pure gliomas of various types showed no immunoreactivity. Our data highlight synaptophysin as a sensitive and specific marker of both neuronal lineage and neoplastic character in gangliogliomas. PMID- 2107139 TI - Bartholin's abscess: the role of Chlamydia trachomatis. AB - Seventy-seven patients with a Bartholin's gland duct disorder were treated by incision and marsupialisation. At operation 18% were found to have a cyst and 82% an abscess. N gonorrhoea was isolated from four abscesses and C trachomatis from one. Bacteriological examination of the uterine cervix yielded one further case of N gonorrhoea and four more of C trachomatis. N gonorrhoea and C trachomatis are of limited aetiologic importance as causes of Bartholin's duct abscess. However, bacteriological examination for STD of the abscess and the cervix is mandatory because of adequate antibiotic treatment of the patients and their contacts. PMID- 2107140 TI - Ciprofloxacin resistant Neisseria gonorrhoeae in the UK. PMID- 2107141 TI - Use of a quality assurance scheme in a long-term multicentric study of antibiotic susceptibility of Neisseria gonorrhoeae. AB - Experience with a quality control programme for a multicentric collaborative study of antibiotic susceptibility of Neisseria gonorrhoeae is described. The Australian Gonococcal Surveillance Programme (AGSP) has monitored the antibiotic sensitivity of gonococci by surveying results of quantitative sensitivity tests performed in a number of centres throughout the country since 1981. A standardised system of testing by means of agar plate dilution was adopted to ensure uniformity of methods and results and to permit temporal and regional differences in antibiotic sensitivity to be identified and compared. A control programme was developed to provide quality assurance regarding each laboratory's performance. Over a period of nine years more than 3600 MIC determinations on control strains, examined as unknowns, were performed. An overall error rate of 3.1% was observed. Higher error rates were noted in the beginning of the programme but these declined as the study progressed. In addition repeat and duplicate testing of strains was performed. The results of these tests also indicated an improvement in performance over the study period. Close attention to all aspects of the testing procedure reduced the number of errors recorded. At the beginning of the programme, various factors were investigated as possible causes of error. The formulation and preparation of media were found to be potential sources of result variation. Once these variables were controlled, lack of experience with end-point determination and errors in preparation of dilutions of antibiotic solutions emerged as the commoner causes of discrepancy. In the experience of the AGSP, a long-term multicentric evaluation of gonococcal sensitivity can achieve accurate and reproducible results through standardisation of methods and application of a continuing quality assurance scheme. PMID- 2107142 TI - Binding of monoclonal antibodies and T cell effector function in vivo. AB - The capacity of adoptively transferred CD8+ effector T cells to induce meningitis in immunosuppressed, or unsuppressed, recipients infected with lymphocytic choriomeningitis virus (LCMV) may be diminished by prior incubation of the lymphocytes with IgM monoclonal antibodies (MAbs) specific for CD8 or Thy1.2. The same is true, though to a lesser extent, for the further proliferation of donor T cells in the spleens of the immunosuppressed mice. This inhibition of cell mediated immunity can be overcome, at least for the unsuppressed recipients, by increasing the numbers of cells that are transferred, even though exposure to Mab+ complement abrogates all cytotoxic T cell activity in vitro. The LCM model thus provides a quantitative system for assessing the consequences of MAb binding for T cell trafficking and effector function in vivo. PMID- 2107143 TI - Synergism between AS101 and PMA in lymphokine production. AB - AS101 [ammonium trichloro (dioxyethylene-o-o') tellurate] has been reported to stimulate normal mouse and human lymphoid cells to proliferate and to produce lymphokines such as interleukin-2 (IL-2) and colony-stimulating factor (CSF), regulators of lymphopoiesis and myelopoiesis. In this study, we demonstrate that the IL-2 secretion and cell proliferation of both human and mouse lymphocytes, and the production of CSF by mouse spleen cells, was significantly enhanced by the synergistic effect of AS101 and phorbol myristate acetate (PMA). AS101 induced activation was found to be very sensitive to inhibition by EGTA, the Ca2+ channel blocker, nifedipine, and cyclosporin A (CsA), an agent which selectively suppresses Ca2(+)-activated steps in this process. Our results suggest that AS101 may efficiently trigger the Ca2+ signal required to initiate lymphocyte activation, but that the enhancement observed when cells are stimulated with both AS101 and PMA may be due to the generation of a second signal, probably the activation of protein kinase C (PKC). A more thorough understanding of the mechanism of action of the immunomodulator AS101, presently under clinical trials on cancer and AIDS patients, is highly relevant to the assessment of its optimal application. PMID- 2107144 TI - Role of TNF and IL-1 in infections with Toxoplasma gondii. AB - Mice lethally infected with the C56 strain of Toxoplasma gondii and treated with purified recombinant murine tumour necrosis factor (TNF, 1 microgram/day/mouse for 8 days), recombinant human interleukin-1 (IL-1 alpha or IL-1 beta, 100 ng/day/mouse for 5 days) or a single dose of a combination of TNF (1 microgram/mouse) and IL-1 alpha or IL-1 beta (100 ng/mouse) were significantly protected against death (P less than 0.05-0.001, as compared with untreated infected controls). Mice infected with 100,000 tachyzoites of the highly virulent RH strain of T. gondii released serum TNF in relation to the time after infection and were primed to secrete an enhanced level of serum TNF upon stimulation with bacterial lipopolysaccharide (LPS). In vitro studies showed that interferon-gamma (IFN-gamma) increased the antimicrobial activity of murine peritoneal macrophages whereas TNF, IL-1 alpha and IL-1 beta did not. TNF, however, synergized with the anti-toxoplasmic effect provided by IFN-gamma and this activity was blocked by anti-TNF antibodies. IFN-gamma induced the production of TNF and the anti toxoplasmic effect provided by IFN-gamma seemed to be dependent partly on the production of TNF. We conclude that TNF and IL-1 may play a significant role in modulating the host's immune defence against T. gondii infection. PMID- 2107145 TI - Epidermal growth factor and transforming growth factor-alpha suppress HLA class II induction in human thyroid epithelial cells. AB - Inappropriate expression of HLA class II by human thyroid epithelial cells (thyrocytes) occurs in autoimmune thyroid diseases where it may contribute to the pathogenesis. Several substances have been found to induce or up-regulate thyrocyte HLA class II expression in vitro. The present investigations show that the induction of HLA class II in human thyrocytes cultured with interferon (IFN) gamma can be partially suppressed by exposure of the thyrocytes to epidermal growth factor (EGF): this occurs when the thyrocytes are treated with the two reagents simultaneously and also when the exposure to EGF is before or after that with IFN-gamma. Concentrations of EGF at least as low as 0.1 ng/ml show this inhibitory effect, which can be over-ridden by very high concentrations of IFN gamma. Thyrocyte HLA class II expression stimulated by thyroid-stimulating hormone (TSH) (in the presence or absence of IFN-gamma) is also suppressed by EGF. Transforming growth factor-alpha (TGF alpha), which is structurally related to EGF and interacts with the same cell surface receptor, has a similar inhibitory activity on the induction of thyrocyte HLA class II expression. The existence of substances which can down-regulate, as well as those which can up regulate, thyrocyte HLA class II expression raises the possibility that the occurrence of such expression in vivo may be determined by the balance between factors with opposing modulatory effects. PMID- 2107146 TI - Differential effects of LPS, IFN-gamma and TNF alpha on the secretion of lysozyme by individual human mononuclear phagocytes: relationship to cell maturity. AB - Human mononuclear phagocytes can be activated to perform a variety of complex functions by exposure to the immunomodulators, lipopolysaccharide (LPS), interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF alpha). Although such activation often involves the release of various cytokines by monocytes and macrophages, little is known of the effects of such signals on their secretion of lysozyme (LZM). In this study, a reverse haemolytic plaque assay for LZM secretion is coupled with immunocytochemistry for the pan macrophage (CD68) marker, EBM/11. This enabled the direct effects of LPS, IFN gamma and TNF alpha on the secretion of LZM by individual, immunoidentified human mononuclear phagocytes to be investigated. The overall secretion of this peptide by populations of freshly isolated or 3-day cultured monocytes was augmented by exposure for 6 hr to bacterial LPS, recombinant human IFN-gamma or recombinant human TNF alpha. Extension of the culture period for monocytes from 3 to 7 days prior to use in the assay resulted in higher levels of LZM secretion, which could be further increased by TNF alpha but not by LPS or IFN-gamma. Individual peritoneal macrophages activated by inflammation in vivo were uniform in their augmented LZM responses to TNF alpha, but a small subpopulation of human peritoneal macrophages, which may represent younger 'inflammatory' exudate macrophages, was seen to be preferentially responsive to the LZM-stimulating effects of LPS and IFN-gamma. These studies suggest that (i) secretion of LZM by human mononuclear phagocytes can be regulated by LPS and IFN-gamma, although the effects of these agents may be dependent upon the state of maturation and/or differentiation of the cells, and (ii) TNF alpha is a potent stimulant of LZM secretion by monocytes and macrophages irrespective of cell maturity. PMID- 2107147 TI - Clinical significance of Staphylococcus aureus in cystic fibrosis. AB - Staphylococcus aureus is usually the first bacterial pathogen detected in the respiratory secretions of patients with cystic fibrosis. This review briefly examines the characteristics of this host-parasite relationship in terms of current knowledge about the toxicity of the organism, mechanisms of respiratory tract injury, therapy and prevention. Recent evidence indicates that viral infection plays a role in the initial damage of the respiratory epithelial cells and staphylococcal colonization ensues. Affinity of staphylococcus for cystic fibrosis mucus, mucociliary abnormalities and unknown factors contribute to persistent colonization with this organism causing progressive pulmonary damage and possibly influencing Pseudomonas infection. Most of the evidence today indicates that aggressive antibiotic management directed against S. aureus is warranted in all stages of bronchopulmonary infection in cystic fibrosis. Future efforts to prevent colonization and the toxic and immunopathic consequences of staphylococcal infection are also important. One study is in progress that examines antibiotic prevention in the early stages of cystic fibrosis. Future investigations need to address other strategies including vaccines, antitoxins, anti-inflammatory agents, immunomodulators, and antibiotic regimens. PMID- 2107148 TI - The role of bacterial adhesion in cystic fibrosis including the staphylococcal aspect. AB - The bacteriology of cystic fibrosis shows a unique and predictable progression of colonizing micro-organisms. The reason for this sequence is still not known, but thought must be given to the idea that it may be related to the genetic disorder in some way. If this were to be true, an understanding of the colonization mechanisms at all stages in this progression could provide valuable insights for the development of novel therapies. As far as can be ascertained from published studies, mucus is the site of colonization in cystic fibrosis. While there is no doubt that the major pathogen, Pseudomonas aeruginosa, adheres to injured cells more avidly than to intact cells, the overwhelming evidence indicates that it also attaches more avidly to mucus than to intact airway cells by means of specific adhesin-receptor mechanisms. Studies with Staphylococcus aureus, the other major pathogen, are also in progress. These indicate that this organism also has an affinity for mucus. At this time the studies suggest a lesser affinity than P. aeruginosa, at least with adult mucins. These two organisms do not however appear to share the same receptor. In addition to these two major pathogens, Haemophilus influenzae and Streptococcus pneumoniae, pathogens of lesser importance also adhere to mucus. Therefore adhesion to mucus or mucins may be a recurring theme in all airway colonization. A knowledge of the factors which control these tropisms ought to provide insights into the bacterial specificity seen in cystic fibrosis and other diseases. PMID- 2107149 TI - Studies of chemotactic, chemotactic movement-inhibiting and random movement inhibiting effects of interleukin-1 alpha and beta, tumour necrosis factors alpha and beta and interferon gamma on human neutrophils in assays using 'sparse-pore' polycarbonate (Nuclepore) membranes in the Boyden chamber. AB - Interleukin-1 alpha and beta (IL-1 alpha and beta), tumour necrosis factors alpha and beta (TNF alpha and beta) and interferon gamma (IFN gamma) were tested for their chemotactic effects, their effects on chemotactic movement towards N-formyl methionyl-leucyl-phenylalanine (FMLP) and their effects on random locomotion of human peripheral blood neutrophils through polycarbonate membranes in Boyden-type chambers. Both IL-1 alpha and beta, but no other cytokine tested were chemotactic for neutrophils using 'sparse-pore' polycarbonate membrane. Both TNFs, but no other cytokine, inhibited neutrophil chemotactic movement towards FMLP using the same membrane. No cytokine influenced random migration of neutrophils through polycarbonate membrane of standard pore density. These results suggest that IL-1 may have a role as a chemotactic mediator of inflammation, but that TNFs may inhibit chemotactic migration of neutrophils into inflammatory lesions. PMID- 2107150 TI - Combined sotalol and flecainide given at low dosage in patients with the Wolff Parkinson-White syndrome. AB - We determined the effects of combined sotalol (160 mg/day) and flecainide (200 mg/day) in 15 patients with the Wolff-Parkinson-White syndrome. After medication given for 3 days, the plasma levels were 0.8 +/- 0.3 micrograms/ml for sotalol and 232 +/- 104 ng/ml for flecainide. Electrophysiologic testing showed complete blockade of the accessory pathway in 4 patients and a decrease in the anterograde conduction capacity by 27% in the remainder. The effect on the accessory pathway was unrelated to the resting conduction properties. Initiation of circus movement tachycardia was prevented in 5 of 11 patients. During a median period of 28 months of follow-up, 87% of patients were either free of tachycardia or satisfactorily improved. No proarrhythmic or adverse drug effects were observed. PMID- 2107151 TI - Efficacy of mitomycin C against alveolar Echinococcus. AB - Mitomycin C was tested against the metacestode stage of Echinococcus multilocularis in jirds. The efficacy of 61-76% was achieved within 1 month of treatment with a total dose of 0.04, 0.08 or 0.3 mg. PMID- 2107152 TI - Optimizing radiologic costs in the DRG environment. AB - Previously developed consensus algorithms expressing a suggested radiologic workup for the diagnostic related groups (DRGs) specified by the prospective reimbursement policy have proven to be useful tools for investigating radiologic decision making and the resulting economic implications. The mathematical equations for determining diagnostic and therapeutic costs for two alternative algorithms for suspected acute cholecystitis are formulated. Illustrative examples and graphic displays are given regarding how such algorithms and equations are useful in finding answers to questions about the appropriate diagnostic workup, time, and cost. Exploration of the effect of different parameter values on the choice of the appropriate algorithm is illustrated. PMID- 2107153 TI - Choosing death for Nancy Cruzan. PMID- 2107154 TI - Home enteral nutrition via gastrostomy in advanced head and neck cancer patients. AB - We investigated whether home enteral feeding via a tube gastrostomy would enable patients with advanced malignant disease, who were unable to maintain themselves nutritionally via the oral route, to be independent of the hospital setting. Thirty-nine patients with advanced upper gastrointestinal and head and neck cancer had a tube gastrostomy placed. Before discharge, the patient was trained in the care and use of the gastrostomy feeding tube. Ten patients died of their disease before they could be discharged. During the 6-month period before gastrostomy insertion, the mean weight loss of the remaining 29 patients was 12.8%, and the mean body weight was less than 90% of ideal body weight. Prior to operation, the mean serum albumin and total lymphocyte count were 3.7 g/L and 1,087/mL, respectively. At discharge the mean caloric intake was 1.48 times resting energy expenditure. Home enteral nutrition was provided for a median of 94 days and resulted in stabilization of nutritional indices. During their median survival of 176 days, the 29 patients were admitted a total of 52 times. Twenty eight percent of the patients were never re-admitted after gastrostomy and were adequately maintained at home, whereas 24% needed to be re-admitted once. Only 48% were re-admitted twice to assist in their nutritional management. Twenty patients received temporary home nursing services to aid in their transition. Four patients eventually resumed oral intake, and their feeding gastrostomies were removed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107155 TI - Changes in case mix and outcomes of readmissions to nursing homes between 1980 and 1984. AB - This study compares the personal characteristics, measures of functional status/case mix, and immediate discharge outcomes of two cohorts of nursing home patients (1980 and 1984). All of these patients had a prior history of nursing home care and all were readmitted to skilled nursing facilities from hospitals. In 1984, readmissions were more disabled, more debilitated, and significantly less likely to return home. They were almost twice as likely to be rehospitalized within 30 days of discharge from the hospital (26.7 percent versus 48.9 percent). Analyses showed poorer health status and an increased proportion of nursing home deaths and rehospitalizations in the 1984 group to be a function of time (1984 versus 1980) rather than of insurance coverage (Medicare versus other). Nursing home readmissions appear to be quite sensitive to cost-containment efforts, and they may require additional hospital days to stabilize their conditions in an effort to reduce the rate of hospital readmissions and the overall cost of care. PMID- 2107156 TI - The diagnostic challenge of styloid elongation (Eagle's syndrome). AB - Eagle's syndrome is a relatively common disorder that is frequently misdiagnosed. It occurs more frequently in women. Presenting symptoms generally include posterior oropharyngeal pain, intermittent glossitis, and phantom foreign body discomfort of the pharynx. Surgical removal of elongated styloid processes generally provides relief of symptoms. PMID- 2107157 TI - Brucella abortus infection in 14 farm dogs. AB - Fourteen dogs were obtained from 10 farms with Brucella-infected cattle and were studied for periods ranging from 2 to 81 days. At necropsy, Brucella abortus biovar 4 was isolated from all 14 dogs. Mandibular, medial retropharyngeal, tracheobronchial, and mesenteric lymph nodes yielded the highest rate of recovery. Urogenital infection with active shedding was seen in a single aged bitch. Fecal samples (291 from 13 dogs) were B abortus culture negative. Ten dogs monitored serologically over time had standard tube agglutination test titers that fluctuated between 1:50 with incomplete reaction and greater than or equal to 1:200 with positive reaction. At necropsy, the magnitude of seroconversion was not directly related to the number of culture-positive tissues. The maximal duration of infection, based on the time interval between the last possible exposure to infected cattle and recovery of the organism at necropsy, was 464 days. If it were assumed that infection occurred at about the same time as seroconversion in the cattle herd of origin, maximal observed duration of infection was 539 days. The actual maximal duration of infection could not be determined from this study, but would have exceeded the values reported here. The data indicate that dogs have the potential to infect cattle and could pose a threat for longer duration of disease transmission than had previously been assumed. Although the risk of transmission appears small, infection of human beings or cattle associated with Brucella-infected dogs would cause unfavorable political and economic consequences, particularly in low-incidence areas. Removal of contact dogs from infected herds should prevent such transmission. PMID- 2107158 TI - Plasma von Willebrand factor concentration and thyroid function in dogs. AB - Plasma von Willebrand factor antigen concentration was determined in 15 dogs with suspected hypothyroidism, in 1 dog with hyperthyroidism, and in 14 euthyroid dogs. The mean +/- SEM von Willebrand factor:antigen concentration in hypothyroid dogs (47.1% +/- 12.6%) was significantly decreased (P less than 0.0005), compared with that in euthyroid dogs (94.7 +/- 5.6%). Four hypothyroid dogs were given thyroxine for 1 month and all 4 had an increase in von Willebrand factor:antigen concentration. The plasma von Willebrand factor:antigen concentration was 200% in the hyperthyroid dog. Seemingly, reduced concentrations of plasma von Willebrand factor:antigen can be found in dogs in association with congenital von Willebrand disease or with von Willebrand disease acquired through hypothyroidism. PMID- 2107159 TI - In vitro interactions of calmodulin with the ovine proacrosin-acrosin system. AB - The authors studied the interaction of calmodulin (CaM) with proacrosin and acrosin from ram spermatozoa. CaM binding evaluated by the [125I]-CaM overlay procedure was shown to occur preferentially with both proacrosin and acrosin in the presence of EGTA; in the presence of Ca2+, the interaction was less intense. Further studies with native proenzyme preparations showed that proacrosin activation at pH 7.1 or 8.0 was significantly accelerated in the presence of CaM and EGTA (t1/2 = 23 min vs. 55 min for EGTA alone at pH 7.1), but not in the presence of Ca2+ (t1/2 = 73 min). The enzymatic activity of acrosin towards benzoyl arginine paranitroanilide, however, was not significantly affected by CaM whether Ca2+ was absent or present. Finally, the authors demonstrated that acrosin hydrolyzed CaM rapidly and extensively in the presence of EGTA. These results indicate that CaM interacts in vitro with proacrosin and acrosin, and that acrosin can attenuate CaM activity through proteolysis. Whether these interactions also occur in vivo and are involved in some aspects of spermatozoa function remains to be determined. PMID- 2107160 TI - Active immunization of pigs against growth hormone-releasing factor: effect on concentrations of growth hormone and insulin-like growth factor 1. AB - Cyclic gilts (96 +/- 1 kg) were used to determine the effect of active immunization against growth hormone-releasing factor GRF(1-29)-NH2 on concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Gilts were immunized against GRF conjugated to human serum albumin (GRF-HSA, n = 5) or HSA alone at 180 d of age (wk 0). Booster doses were administered at wk 9 and 13. Seven days after the second booster (wk 14), blood samples were collected at 15-min intervals for 6 h before feeding and 30, 60, 120, 180 and 240 min after feeding. Eight days after the second booster, all gilts were administered a GRF analog, [desNH2Tyr1,Ala15]-GRF(1-29)-NH2, followed by an opioid agonist, FK33 824. Blood samples were collected at 15-min intervals from -30 to 240 min after injection. Immunization against GRF-HSA resulted in antibody titers, expressed as dilution required to bind 50% of [125I]GRF, ranging from 1:11,000 to 1:60,000 (wk 11 and 14); binding was not detectable or was less than 50% at 1:100 in HSA gilts (P less than .05). Episodic release of GH was abolished by immunization against GRF-HSA (P less than .05). Mean GH was decreased (P less than .07), but basal GH concentrations were not altered (P greater than .15) by immunization against GRF HSA. Serum concentrations of IGF-1 were similar at wk 0, but concentrations were lower in GRF-HSA than in HSA gilts (P less than .05) at wk 14.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107161 TI - Lysine and methionine transport by bovine jejunal and ileal brush border membrane vesicles. AB - Lysine (LYS) and methionine (MET) transport were studied using brush border membrane vesicles from bovine jejunal and ileal tissues. Total transport of LYS and MET was divided into mediated and diffusion components. Mediated uptake was further divided into sodium (Na)-dependent and Na-independent systems. Total LYS and MET uptake by ileal brush border (BB) vesicles tended to be higher than that by jejunal BB vesicles at all concentrations evaluated but differences were significant (P less than .05) at 2.5 and 7.5 mM for LYS and 5, 12.5 and 15 mM for MET. The greater capacity of ileal BB vesicles appeared to be due to the Na dependent component of LYS uptake and the diffusion component of MET uptake. Transporters had less affinity but higher capacity than for LYS transport in both ileal and jejunal tissue. Methionine transport was greater (P less than .05) than LYS transport in both ileal and jejunal BB vesicles when the initial amino acid concentration was 7.5 mM. But when the initial amino acid concentration was 1.25 mM, MET uptake was greater (P less than .13) than LYS uptake in jejunal, but not in ileal, BB vesicles. The relative contribution of mediated and diffusion uptake systems to total MET and LYS uptake was found to be dependent on substrate concentration. Both intestinal site and substrate concentration influenced the contributions of Na-dependent, Na-independent and diffusion systems to total methionine and lysine uptake. PMID- 2107162 TI - Isolation and propagation of phages naturally associated with the aizawai variety of Bacillus thuringiensis. AB - This study describes the isolation of a phage, using mitomycin C and u.v. light, from each of four strains (HD67, HD130, HD228 and HD248) of Bacillus thuringiensis H-serotype 7 (var. aizawai). It also describes the isolation of two indicator strains (12.13 and HD102) for these phages (phi HD67, phi HD130, phi HD228 and phi HD248) and the ideal conditions, using these indicator strains, for maximum phage production. PMID- 2107163 TI - Development of an expert system for bacterial identification: study of a prototype for identifying beta-galactosidase positive enterobacteria. AB - A prototype of an expert system for the identification of beta-galactosidase positive Enterobacteriaceae has been developed, for use with the API 20 EC kit. The system is implemented in Prolog on an IBM PC AT with 640 K of central memory and 20 megabytes of secondary memory. Its objectives are to highlight errors that can occur when the kit is in use. It can indicate the presence of new groups or species and give advice or suggest additional tests for the differentiation of the new species from those included in the kit. PMID- 2107164 TI - Control of pH of airway surface liquid of the ferret trachea in vitro. AB - We measured the pH of airway surface liquid (ASL) secreted by the ferret trachea in vitro by using a catheter-tipped pH electrode implanted in a collecting cannula close to the airway epithelium. Mucus secretion was promoted by methacholine (0.02 mmol/l) in the organ bath. The pH of the ASL was 6.85 +/- 0.03 (SE) compared with a bath value of 7.39 +/- 0.01, when the bath was bubbled with 5.65% CO2. Changing the bath CO2 from 0 to 20.93% CO2 altered the bath pH from 8.06 to 6.96, but the ASL pH only varied from 6.92 to 6.85. This homeostasis of ASL pH was not the result of the buffering powers of the ASL, because ex situ buffer curves for secreted ASL were similar to those for Krebs-Henseleit solution. Changing the luminal CO2 content by blowing gases through the trachea changed ASL pH by values similar to that ex situ. However, when external organ bath CO2 was changed, the luminal CO2 changes were proportionately far smaller. Measurement of rates of diffusion of CO2 across the tracheal wall indicated that this was not a limiting factor in the results. Similarly, measurement of metabolic rate CO2 production in the tracheal lumen indicated that this did not significantly affect the results. We conclude that the pH of ASL is significantly on the acid side of the pH or interstitial fluid and plasma and that it is maintained relatively constant despite large changes in external pH. PMID- 2107165 TI - Plasma [H+] regulation and whole blood [CO2] in exercising ponies. AB - The major objective was to determine in ponies whether factors in addition to changes in blood PCO2 contribute to changes in plasma [H+] during submaximal exercise. Measurements were made to establish in vivo plasma [H+] at rest and during submaximal exercise, and CO2 titration of blood was completed for both in vitro and acute in vivo conditions. In 19 ponies arterial plasma [H+] was decreased from rest 4.5 neq/l (P less than 0.05) during the 7th min of treadmill running at 6 mph, 5% grade (P less than 0.5). A 5.6-Torr exercise hypocapnia accounted for approximately 2.9 neq/l of this reduced [H+]. The non-PCO2 component of this alkalosis was approximately neq/l, and it was due presumably to a 1.7-meq/l increase from rest in the plasma strong ion difference (SID). Despite the arterial hypocapnia, mixed venous PCO2 was 2.7 Torr above rest during steady state exercise. Nevertheless, mixed venous plasma [H+] was 1.2 neq/l above rest during exercise, which was presumably due to the increase in SID. Also studied was the effect of submaximal exercise on whole blood CO2 content (CCO2). In vitro, at a given PCO2 there was minimal difference in CCO2 between rest and exercise blood, but plasma [HCO3-] was greater for exercise blood than for rest blood. In vivo, during steady-state exercise, arterial plasma blood. In vivo, during steady-state exercise, arterial plasma [HCO3-] was unchanged or slightly elevated from rest, but CaCO2 was 4 vol% below rest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107166 TI - In vivo regulation of plasma [H+] in ponies during acute changes in PCO2. AB - The major objective of this study was to test the hypothesis that in ponies the change in plasma [H+] resulting from a change in PCO2 (delta H+/delta PCO2) is less under acute in vivo conditions than under in vitro conditions. Elevation of inspired CO2 and lowering of inspired O2 (causing hyperventilation) were used to respectively increase and decrease arterial PCO2 (Paco2) by 5-8 Torr from normal. Arterial and mixed venous blood were simultaneously sampled in 12 ponies during eucapnia and 5-60 min after Paco2 had changed. In vitro data were obtained by equilibrating blood in a tonometer at five different levels of PCO2. The in vitro slopes of the H+ vs. PCO2 relationships were 0.73 +/- 0.01 and 0.69 +/- 0.01 neq.1-1.Torr-1 for oxygenated and partially deoxygenated blood, respectively. These slopes were greater (P less than 0.001) than the in vivo H+ vs. PCO2 slopes of 0.61 +/- 0.03 and 0.57 +/- 0.03 for arterial and mixed venous blood, respectively. The delta HCO3-/delta pH (Slykes) was 15.4 +/- 1.1 and 17.0 +/- 1.1 for in vitro oxygenated and partially deoxygenated blood, respectively. These values were lower (P less than 0.001) than the in vivo values of 23.3 +/- 2.7 and 25.2 +/- 4.7 Slykes for arterial and mixed venous blood, respectively. In vitro, plasma strong ion difference (SID) increased 4.5 +/- 0.2 meq/l (P less than 0.001) when Pco2 was increased from 25 to 55 Torr. A 3.5-meq/l decrease in [Cl-] (P less than 0.001) and a 1.3 +/- 0.1 meq/l increase in [Na+] (P less than 0.001) accounted for the SID change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107167 TI - Cardiac receptors evoke ventilatory response with increased venous PCO2 at constant arterial PCO2. AB - The effects of elevated venous PCO2 and denervation of the cardiac ventricles on ventilation were studied in 20 anesthetized open-chest unidirectionally ventilated White Leghorn cockerels. Venous PCO2 was increased by insufflating the gut with high CO2 while recording changes in the amplitude of the sternal movements. Arterial blood gases were held constant by unidirectionally ventilating the lungs with gas flows approximately five times the animal's resting minute volume. Insufflating the gut with 90% N2-10% O2 did not change the level of ventilation, whereas with 90% CO2-10% O2 the amplitude of sternal movement increased 500% above that with no gut gas flow. Exchange of N2 for the CO2 was followed by a rapid reduction of ventilatory movements to control levels. Arterial blood gases remained constant during gut gas insufflation, whereas mixed venous PCO2 increased and mixed venous pH decreased when high CO2 was given to the gut. Cutting the middle cardiac nerves, which primarily innervate the ventricles of the heart, reduced the ventilatory response to CO2 gut insufflation by 67%. Sympathetic denervation of the thoracic viscera did not change the responses. It appears that, in the chicken, increasing the mixed venous PCO2 while holding the arterial blood gases constant alters ventilation by an afferent system located in the venous circulation or in the right ventricle which is sensitive to changes in PCO2. PMID- 2107168 TI - A model-based evaluation of the single-breath CO2 ventilatory response test. AB - The accuracy of the single-breath CO2 inhalation test as a method for determining peripheral chemoreflex gain (Gp) is evaluated through computer simulations using a mathematical model of the closed-loop respiratory control system. Estimates of Gp (G'p) are based on "corrected" changes in end-tidal PCO2, because the uncorrected end-tidal values do not accurately reflect changes in alveolar PCO2. The influence of the central chemoreflex on G'p is generally less than 10% but can become disproportionally more significant as the relative contribution of the peripheral chemoreflex diminishes. G'p tends to overestimate Gp with the inclusion of peripheral chemoreceptor rate sensitivity, but this effect is offset by the time constant for adaptation. The spontaneous variability of breathing can seriously impair the resolution of G'p. Averaging of G'p deduced from individual single-breath tests can lead to erroneous estimates of Gp even when a large number of repetitions are performed. This problem can be minimized by first ensemble averaging the data from individual single-breath tests and, then, computing G'p from the resulting mean changes. PMID- 2107169 TI - Cervical sympathetic and phrenic nerve responses to progressive brain hypoxia. AB - To determine if depression of central respiratory output during progressive brain hypoxia (PBH) can be generalized to other brain stem outputs, we examined the effect of PBH on the tonic (tSCS) and inspiratory-synchronous (iSCS) components of preganglionic superior cervical sympathetic (SCS) nerve activity. Peak phrenic and SCS activity were measured in nine anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats. PBH was produced by inhalation of 0.5% CO in 40% O2 while blood pressure and end-tidal CO2 were maintained constant. A progressive reduction in arterial O2 content from 14.3 +/- 0.6 to 4.5 +/- 0.3 vol% caused a 79 +/- 7% depression of peak phrenic activity and an 84 +/- 10% reduction of iSCS activity, but tSCS activity increased 42 +/- 21%. During CO2 rebreathing, iSCS activity increased in parallel with peak phrenic activity while tSCS activity was unchanged. The slopes of the CO2 responses of both phrenic (6.3 +/- 1.2%max/mmHg) and iSCS (4.6 +/- 0.8%max/mmHg) activity were unaffected by PBH. In four of nine hypocapnic and three of nine hypoxic studies, inspiratory activity in the SCS nerve was observed even after completely silencing the phrenic neurogram.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107170 TI - Shivering and cardiorespiratory responses during normocapnic hypoxia in the pigeon. AB - To study the inhibitory effect of hypoxia on the cold defense mechanism, pigeons were exposed at low ambient temperature (5 degrees C) to various inhaled gas mixtures: normoxia [0.21 fractional concentration of O2 (FIO2)], hypoxia (0.07 FIO2), and normocapnic hypoxia (0.07 FIO2 + 0.045 FICO2). Electromyographic (EMG) activity indicative of shivering thermogenesis was inhibited during hypoxia, and body temperature (Tre) fell by 0.09 degrees C/min. Respiratory frequency (f) and minute ventilation (VE) increased by 143 and 135%, respectively, compared with normoxia, but tidal volume (VT) was not changed. PO2, PCO2, and O2 contents in the arterial and mixed venous blood were decreased and pH was enhanced. During normocapnic hypoxia, shivering EMG was present at approximately 50% of the normoxic intensity; Tre fell by only 0.04 degrees C/min. Arterial and mixed venous PCO2 and pH were the same as during normoxia, but VE increased by 430% because of twofold increases in both f and VT. During normocapnic hypoxia, arterial PO2 and O2 content were higher than during hypoxia alone. We conclude that the persistence of shivering during normocapnic hypoxia is due to maintenance of critical levels of arterial PO2 and O2 content. PMID- 2107171 TI - Mechanisms of gas exchange with different gases during constant-flow ventilation. AB - To investigate the mechanisms responsible for the difference in gas exchange during constant-flow ventilation (CFV) when using gases with different physical properties, we used mixtures of 70% N2-30% O2 (N2-O2) and 70% He-30% O2 (He-O2) as the insufflating gases in 12 dogs. All dogs but one had higher arterial PCO2 (PaCO2) with He-O2 compared with N2-O2. At a flow of 0.37 +/- 0.12 l/s, the mean PaCO2's with N2-O2 and He-O2 were 41.3 +/- 13.9 and 53.7 +/- 20.3 Torr, respectively (P less than 0.01); at a flow rate of 0.84 +/- 0.17 l/s, the mean PaCO2's were 29.1 +/- 11.3 and 35.3 +/- 13.6 Torr, respectively (P less than 0.01). The chest was then opened to alter the apposition between heart and the lungs, thereby reducing the extent of cardiogenic oscillations by 58.4 +/- 18.4%. This intervention did not significantly alter the difference in PaCO2 between N2 O2 and He-O2 from that observed in the intact animals, although the individual PaCO2 values for each gas mixture did increase. When the PaCO2 was plotted against stagnation pressure (rho V2), the difference in PaCO2 between N2-O2 and He-O2 was nearly abolished in both the closed- and open-chest animals. These findings suggest that the different PaCO2's obtained by insufflating gases with different physical properties at a fixed flow rate, catheter position, and lung volume result mainly from a difference in the properties of the jet. PMID- 2107172 TI - Gas exchange abnormalities after pneumonectomy in conditioned foxhounds. AB - Loss of a major portion of lung tissue has been associated with impaired exercise capacity, but the underlying mechanisms are not well defined. We studied the alterations in gas exchange during exercise before and after left pneumonectomy in three conditioned foxhounds. After pneumonectomy, minute ventilation and O2 consumption at comparable submaximal work loads were unchanged but arterial PCO2 at any work load was higher, implying that ventilatory response to CO2 was impaired. Arterial hypoxemia and an elevated alveolar-arterial O2 tension difference (AaDO2) developed during heavy exercise. Using the multiple inert gas elimination technique, we determined the distributions of ventilation-perfusion (VA/Q) ratios postpneumonectomy. Significant increase in VA/Q inequality developed during exercise while the foxhounds were breathing room air, accounting for an average of 42% of the total increase in AaDO2 while diffusion limitation accounted for 58%. While the animals were breathing hypoxic gas mixture, diffusion limitation accounted for an average of 88% of the total increase AaDO2. Cardiac output and O2 delivery were reduced at a given O2 consumption after pneumonectomy. After pneumonectomy, the animals reached O2 consumptions close to the maximum expected for normal dogs. Compensation for the impairment in O2 delivery post-pneumonectomy occurred mainly by an increase in hemoglobin concentration. Training probably played an important role in returning exercise capacity toward prepneumonectomy levels. We conclude that significant abnormalities in gas exchange develop during exercise after loss of 42% of lung tissue, but the animals demonstrate a remarkable ability to compensate for these changes. PMID- 2107173 TI - von Willebrand disease. AB - The study of a wide variety of patients with vWD disorders has been extensive and intense over the last decade. In many instances the peculiarities of the expressions of the disorder have been critical in defining the underlying structure and function of vWF itself. As our knowledge of the biochemistry and physiology of vWF has grown, significant refinements in both diagnostic and therapeutic modalities have emerged that increasingly provide considerable benefit to the individual patient. PMID- 2107174 TI - Thrombotic thrombocytopenic purpura and related disorders. AB - This article provides us with background information on the disease. Clinical features, variants and classification, laboratory findings, and pathology are discussed. Knowledge of the disease's pathogenesis has increased recently and specific causes discussed are predisposing factors, triggering agents, endothelial damage, defective PGI2 bioavailability, FVIII/vWF multimeric structure abnormalities, platelet activation, and hemolytic anemia. Proposed specific therapies discussed are steroids, heparin, antiplatelet agents, prostacyclin, splenectomy, immunosuppressive agents, plasma infusion, and plasma exchange. PMID- 2107175 TI - In vitro development of one-cell embryos from outbred mice: influence of culture medium composition. AB - One-cell embryos from outbred mice (CF1, CD-1, and Dub:ICR) were cultured in various modifications of egg culture medium (ECM). The best development was observed in medium in which inorganic salts of modified T6 medium (mT6) replaced those of ECM. In this modification (TE), 66% of one-cell CF1 embryos developed into blastocysts, compared to 46 and 43% for ECM and mT6, respectively. Moreover, the cell numbers of blastocysts developing in TE (7.49 +/- 3.3) were higher than the cell numbers of those developing in ECM (55.1 +/- 2.4). The culture requirements of embryos varied between different stocks of mice: Fewer CF1 embryos developed to the blastocyst stage than either Dub:ICR embryos (90%) or CD 1 embryos (84%). Lowering the osmolarity of the medium from 300 to 280 mOSM, increasing the concentration of KC1 from 1.42 to 25 mM, or omitting lactate from the medium during Day 1 of culture did not further improve development of embryos, in contrast to previous reports. However, the time at which embryos were transferred to outgrowth medium influenced their postblastocyst development. The best development was observed when embryos were transferred on Day 4 of culture at the late morula-early blastocyst stage. PMID- 2107176 TI - Pesticide residues in milk and fish samples collected from two Egyptian Governorates. AB - Because of the intensive use of pesticides for the control of certain pests in Egypt, country-wide residue monitoring programs must be established that can cover all the Egyptian Governorates exposed to pesticide treatments. To do so, limited programs must be adopted first, so that current situations and future needs for improved programs are identified. The present paper reports results from a limited monitoring program, which started in 1985 in one governorate and then expanded to include another in 1986. Fish and milk samples were the commodities selected for residue analysis. The results showed that milk samples collected from Beni-Suef Governorate in 1986 had lower levels of organochlorine residues compared to those collected in 1985. Residues in boltifish and catfish samples in 1986 were much higher than those detected in 1985. In comparison with Beni-Suef Governorate, and contrary to expectations, milk derived from Fayoum Governorate in 1986 was more contaminated with pesticides. While the amount of residues in boltifish was comparatively higher, catfish samples were less contaminated. PMID- 2107177 TI - Effects of injection solvent and mobile phase on efficiency in reverse-phase liquid chromatographic determination of aflatoxin M1. AB - The effects of injection solvent and mobile phase composition on the reverse phase liquid chromatographic determination of aflatoxin M1 (M1) were examined. M1 was converted to the more highly fluorescent derivative aflatoxin M2a (M2a). Using a C-18 column and a mobile phase of H2O-MeCN-MeOH (60 + 20 + 20) (MP-A), M2a was dissolved in various ratios of MeCN-H2O prior to injection. Chromatographic efficiency for the M2a peak varied from ca 2000 theoretical plates when injected in 30% aqueous MeCN to ca 9000 plates when injected in water alone. However, using the same C-18 column but with a mobile phase of H2O-IPA MeCN (80 + 12 + 8) (MP-B), the M2a peak exhibited 25,000 plates when injected in 30% aqueous MeCN and 10,000 plates when injected in water alone. PMID- 2107178 TI - Monoclonal antibody-based enzyme linked immunosorbent assay of aflatoxin B1, T-2 toxin, and ochratoxin A in barley. AB - Aflatoxin B1 (B1), T-2 toxin (T2), and ochratoxin A (OA) were assayed in a single extract from barley grain by using competitive enzyme linked immunosorbent assays (ELISAs) with monoclonal antibodies. B1 and T2 monoclonal antibodies were conjugated to horseradish peroxidase for direct competitive ELISA while an indirect competitive ELISA was used for OA determination. The competitive ELISA detected 0.1 ng/mL of B1, 10 ng/mL of T2, or 1 ng/mL of OA. Acetonitrile-0.5% KCl 6% H2SO4 (89 + 10 + 1) extracts of barley grain either were diluted 1:10 for direct assay or were subjected to a simple liquid-liquid cleanup procedure to concentrate the extract 10:1 before assay. For cleanup, water was added to the acetonitrile extract to partition water-soluble interfering substances, and then the mycotoxins were re-extracted with chloroform. The chloroform extract was evaporated to dryness and redissolved in Tris HCl buffer for ELISA. The mean recoveries from barley spiked with 4-60 ng/g of B1, 50-5000 ng/g of T2, and 5-500 ng/g of OA were, respectively, 93.8, 80.6, and 95.8%. The mean within-assay, inter-assay, and subsample coefficients of variation by ELISA of barley grain colonized with toxigenic fungi were less than 12% for B1 and OA but as high as 17% for T2. PMID- 2107179 TI - Immunologic study of artificial skin used in the treatment of thermal injuries. AB - Artificial skin (Integra) has been developed as an effective treatment of full thickness burns. The material consists of a bovine collagen and chondroitin-6 sulfate dermal matrix with a silicone rubber "epidermal" layer. After burn wound excision, the artificial skin is implanted. Only the temporary silicone rubber epidermal membrane is removed. The dermal collagen matrix is incorporated by the host. Serial serum samples were obtained from patients who had grafts of Integra artificial skin for the determination of the humoral immune response to Integra. Integra artificial skin presents few if any humoral immunologic problems to patients. Increased antibody activity to bovine skin collagen, bovine skin collagen with chondroitin sulfate, and human skin collagen was not considered immunologically significant. PMID- 2107180 TI - Carbon dioxide laser burn of laryngotracheobronchial mucosa. AB - A CO2 laser fire in the laryngotracheobronchial tree occurred because of an increase in fraction of inspired oxygen to greater than 40%. An endotracheal tube was ignited and caused a severe burn of respiratory mucosa that required treatment in a burn intensive care unit. The patient had surprisingly few immediate respiratory complications and was discharged from the hospital 25 days after the burn. PMID- 2107181 TI - Branhamella catarrhalis pneumonia with bacteremia in a pediatric patient with smoke inhalation. AB - Branhamella catarrhalis, a common inhabitant of the upper respiratory tract, has been identified recently as a cause of lower airway infection. In this report we present a case of B. catarrhalis pneumonia and bacteremia in a child with smoke inhalation as the first description of invasive disease involving this organism in a traumatized airway. In addition, other pediatric cases of B. catarrhalis bacteremia are reviewed, suggesting immunocompromise as a risk factor. PMID- 2107182 TI - Antineoplastic efficacy of melphalan and N-(2-chloroethyl)-N-nitrosocarbamoyl omega-lysine, in combination with diazoxide or insulin in autochthonous mammary carcinoma of the Sprague-Dawley rat. AB - The anticancer activity of melphalan and N-(2-chloroethyl)-N-nitrosocarbamoyl omega-lysine (CNC-omega-Lys), was compared in the autochthonous, methylnitrosourea-induced mammary carcinoma of the Sprague-Dawley rat. In addition, the influence on the therapeutic efficacy of the combination with diazoxide, causing a mild, reversible diabetes, and with insulin was investigated. The comparison of melphalan and CNC-omega-Lys clearly showed the superiority of melphalan. Both compounds displayed a significant tumour inhibition in their medium and the highest dosages in comparison to the untreated control. The combination with diazoxide resulted for almost all groups in an increased tumour inhibition. Only the lowest dose of CNC-omega-Lys + diazoxide did not reduce the tumour volume significantly versus the control group. The combination with insulin, however, resulted in a loss of tumour inhibition compared to the effect of the cytotoxic drug alone, although in these groups, too, a significant decrease of tumour volumes versus controls could be observed. Mortality was within tolerable limits (less than 20%) through the treatment period for all experimental groups. Median lifespans were increased in all therapy groups, but no additional benefit could be observed in the combination treatment groups. PMID- 2107183 TI - Adenine nucleotides modulate phosphatidylcholine metabolism in aortic endothelial cells. AB - ATP and ADP, in concentrations ranging from 1-100 microM, increased the release of [3H]choline and [3H]phosphorylcholine (P-choline) from bovine aortic endothelial cells (BAEC) prelabelled with [3H]choline. This action was detectable within 5 minutes and was maintained for at least 40 minutes. ATP and ADP were equiactive, and their action was mimicked by their phosphorothioate analogs (ATP gamma S and ADP beta S) and adenosine 5'-(beta, gamma imido) triphosphate (APPNP), but not by AMP, adenosine, and adenosine 5'-(alpha, beta methylene)triphosphate (APCPP): these results are consistent with the involvement of P2Y receptors. ATP also induced an intracellular accumulation of [3H]choline: the intracellular level of [3H]choline was increased 30 seconds after ATP addition and remained elevated for a least 20 minutes. The action of ATP on the release of choline metabolites was reproduced by bradykinin (1 microM), the tumor promoter phorbol 12-myristate 13-acetate (PMA, 50 nM), and the calcium ionophore A23187 (0.5 microM). Down-regulation of protein kinase C, following a 24-hour exposure of endothelial cells to PMA, abolished the effects of PMA and ATP on the release of choline and P-choline, whereas the response to A23187 was maintained. These results suggest that in aortic endothelial cells, ATP produces a sustained activation of a phospholipase D hydrolyzing phosphatidylcholine. The resulting accumulation of phosphatidic acid might have an important role in the modulation of endothelial cell function by adenine nucleotides. Stimulation of phospholipase D appears to involve protein kinase C, activated following the release of diacylglycerol from phosphatidylinositol bisphosphate by a phospholipase C coupled to the P2Y receptors (Pirotton et al., 1987a). PMID- 2107184 TI - Mechanism of human lymphotoxin and tumor necrosis factor induced destruction of cells in vitro: phospholipase activation and deacylation of specific-membrane phospholipids. AB - The role of phospholipase (PLase) activation and lipid metabolism in lymphotoxin (LT)- and tumor necrosis factor (TNF)-mediated destruction of murine L929 cells was examined. At the levels of LT and TNF employed, cell destruction began at 4-6 h and was 99% complete by 30 h. Cell membrane phospholipids (PL), labelled in situ at the C2 position with 14C arachidonic acid, were analyzed by two dimensional thin-layer chromatography and quantitated over a 30 h time course after LT or TNF treatment. The ratio of radiolabel incorporation relative to the actual amount of each PL present was determined by inorganic phosphate analysis. Radiolabelled arachidonic acid, eicosanoids, and neutral lipids were released into the medium prior to the onset of cell death (4-6 h) and continued to accumulate linearly throughout the destructive reaction. There was a quantitative relationship between the appearance of radiolabelled metabolites in the media and the loss of radiolabelled cellular PL. Cellular phosphatidylethanolamine was the primary PL deacylated by PLase action, showing a 75% reduction in radiolabel. The PLase inhibitors--quinacrine, hydrocortisone, dexamethasone, and indomethacin- were potent inhibitors of LT- and TNF-mediated cell destruction, suggesting that selective deacylation of specific membrane PL by PLase activation is an important step in the events that lead to LT- and TNF-mediated cellular destruction in vitro. PMID- 2107185 TI - Heparin and acidic fibroblast growth factor interact to decrease prostacyclin synthesis in human endothelial cells by affecting both prostaglandin H synthase and prostacyclin synthase. AB - Prostaglandin production by cultured human endothelial cells varies with growth conditions. We observed a marked diminution in both spontaneous and inducible production of prostacyclin (PGI2) by human umbilical vein and saphenous vein endothelial cells when they were cultured in the presence of the heparin-binding growth factor, acidic fibroblast growth factor (aFGF) and heparin, compared with PGI2 production during culture in medium lacking these factors. Decreased PGI2 production was related to duration of exposure of the cells to aFGF and heparin and depended on the concentration of both substances. Heparin (1-100 micrograms/ml) strongly potentiated the effects of aFGF but had a limited and variable effect alone. The decrease in PGI2 production correlated with a reduction in the cellular content of immunoreactive prostaglandin H synthase and prostacyclin synthase. Arachidonate deacylation was not decreased. In addition, the eicosanoid profile of endothelial cells was changed by exposure to aFGF and heparin. These studies indicate that heparin acts as a modulator of prostaglandin synthesis in endothelial cells through its interaction with aFGF, mediated by alterations in two key enzymes in the arachidonate metabolic pathway. PMID- 2107186 TI - The imported fire ant: immunopathologic significance. AB - The imported fire ant is a major insect cause of generalized hypersensitivity in the southern United States. The alkaloids in the ant's unique venom also produce substantial morbidity due to local reactions, both toxin- and IgE-mediated. Immunotherapy--with whole body extracts as well as with venom--is given only to patients with systemic reactions. PMID- 2107187 TI - The oath. PMID- 2107188 TI - Alcohol and hypertension. PMID- 2107189 TI - Acute abdomen in a 79-year-old. PMID- 2107190 TI - Diagnosis and decisions by algorithms. PMID- 2107191 TI - Ventricular or supraventricular tachycardia? PMID- 2107192 TI - Pathogenesis of gallstones: implications for management. AB - How do gallstones form, and what can be done to reverse or prevent the process? Bile acid physiology and pathophysiology are reviewed, especially with respect to cholesterol stones, and bile acid treatment to dissolve them is discussed. Although less well understood, the pathogenesis of pigment (black or brown) stones may involve bilirubin or carbonate salts, or infection. PMID- 2107193 TI - Estrogen-progestogen replacement and cancer risk. AB - The increasing popularity of hormone replacement has focused renewed attention on the issue of whether certain sex steroids predispose to--or exert a protective effect against--various forms of carcinoma. In particular, the impact of the sex hormones on the pathogenesis of breast cancer remains highly controversial. Published reports have failed to demonstrate a clear relationship. PMID- 2107194 TI - Decrease in interferon-gamma production by peripheral blood mononuclear cells in patients with uterine cervical cancer. AB - The interferon-gamma (IFN-gamma) productivity of peripheral blood mononuclear cells (PBMCs) was examined in 30 patients with uterine cervical cancer. The patients under 50 years of age had decreased IFN-gamma production compared with the age-matched controls. The IFN-gamma productivity in the patients over 50 years of age was decreased as well as in the age-matched controls. The proportion of monocytes in PBMCs did not correlate with the IFN-gamma productivity. The prostaglandin E2 (PGE2) productivity of PBMCs increased with the progress of cancer. PGE2 inhibited the IFN-gamma production by PBMCs, and the sensitivity of PBMCs to PGE2 was increased in the patients and controls over 60 years of age. The addition of indomethacin resulted in an increase in IFN-gamma production by PBMCs. These results suggest that the increased production of PGE2 and/or increased sensitivity to PGE2 are responsible for the decreased IFN-gamma production in patients with cervical cancer. PMID- 2107195 TI - Normal mitogen-induced suppression of the interleukin-6 (IL-6) response and its deficiency in systemic lupus erythematosus. AB - A low-frequency suppressor-cell population in normal peripheral blood inhibits the B-cell CESS response to IL-6, following pokeweed mitogen stimulation. The suppression of IL-6 responsiveness is (i) radiation sensitive, (ii) directed against CESS targets and not mediated by inhibition of IL-6 production, and (iii) associated with nonspecific cytotoxic activity against CESS targets. The generation of these cytolytic cells is also radiation sensitive. A correlation was found between PWM-induced cytotoxicity against CESS and the suppression of IL 6-dependent IgG production. But cytotoxicity toward CESS targets is not responsible for this suppression because (i) IL-2 induces equivalent or greater nonspecific cytotoxicity against CESS in the total absence of suppression of CESS derived IgG production and (ii) suppression is also induced by mitogen-activated PBL separated from CESS targets by a cell-impermeable membrane. This suppression was not mediated by TNF alpha/beta or IFN-gamma. In systemic lupus erythematosus, suppression of IL-6-dependent IgG production is impaired in patients with active disease (29.2 +/- 13.7%) compared to patients with inactive disease (70 +/- 19.5%) or normal controls (82.8 +/- 9.2%). There is also a defect in mitogen induced nonspecific cytotoxicity in active SLE (specific lysis 15.1 +/- 3.5%, compared to 34 +/- 4% in normals). Pokeweed mitogen-activated PBL can therefore normally induce suppression of B-cell IL-6 responses and this response is deficient in lupus. PMID- 2107196 TI - Rapid presumptive identification of gram-negative rods directly from blood cultures by simple enzymatic tests. AB - Gram-negative rods were presumptively identified directly from blood cultures within 15 min as Escherichia coli, a member of the Klebsiella-Enterobacter group, or oxidase positive. Samples of artificially seeded blood cultures (193 cultures) and patient blood cultures (78 cultures) were filtered into a Dynadepth test card with the Bac-T-Screen instrument (Vitek, Inc., Hazelwood, Mo.). Triton X-100 was then filtered into the test card to lyse the blood cells but not the entrapped bacteria, and either methylumbelliferone-labeled substrates or oxidase reagent was applied to the filter surface. The oxidase test was read within 30 s, and the methylumbelliferone and indole tests were read after a 10-min incubation at room temperature. Positive beta-galactosidase, beta-glucuronidase, and indole test results predicted the identification of E. coli with a 96 to 100% sensitivity and a 99 to 100% specificity. Positive beta-xylosidase and beta-galactosidase test results and negative oxidase and beta-glucuronidase test results were 85 to 93% sensitive and 100% specific for a Klebsiella-Enterobacter organism. A positive oxidase test result and negative beta-glucuronidase, beta-xylosidase, and indole test results were highly predictive of Pseudomonas aeruginosa (sensitivity, 100%; specificity, 99%). The procedures described are rapid and simple and provide a direct presumptive identification of the gram-negative rods most commonly found in blood cultures. PMID- 2107197 TI - Serological typing of Branhamella catarrhalis strains on the basis of lipopolysaccharide antigens. AB - A total of 302 strains of Branhamella catarrhalis from different parts of the world were serologically typed according to their lipopolysaccharide (LPS) antigenicity. For this purpose, an inhibition enzyme-linked immunosorbent assay was developed using the following reagents: antisera raised against whole bacterial suspensions for a panel of 16 serotype strains and LPS prepared from these strains by phenol extraction. Antisera were absorbed with whole bacterial suspensions of the B. catarrhalis strains to be tested. The residual activity of the sera against the homologous LPS was determined by means of an enzyme-linked immunosorbent assay, using microdilution plates coated with LPS. Strains which gave greater than 90% reduction of activity were considered to carry the same LPS type as the serotype strain. It was shown that 93.4% of the strains tested carried one of three possible LPS types. LPS of B. catarrhalis are the rough type and have an apparent Mr of 5,500, as estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. PMID- 2107198 TI - Conversion of Pseudomonas aeruginosa to the phenotype characteristic of strains from patients with cystic fibrosis. AB - Isolates of Pseudomonas aeruginosa from cystic fibrosis patients are unusual; they are often susceptible to the bactericidal effect of human serum, have a rough lipopolysaccharide, and produce an exopolysaccharide that is responsible for the characteristic mucoid phenotype. In contrast, strains from the environment and from patients with other diseases usually have smooth lipopolysaccharide, do not produce very much mucoid exopolysaccharide, and are phenotypically nonmucoid. The predominance of mucoid strains of P. aeruginosa in infections of patients with cystic fibrosis has not been explained. In the lower airways, where P. aeruginosa persists in cystic fibrosis, nutrients for bacterial growth may be limited. We investigated whether growth of P. aeruginosa under conditions of suboptimal nutrition causes conversion to the characteristic cystic fibrosis phenotype. Ninety-two strains of P. aeruginosa were maintained for up to 90 days in a minimal medium with acetamide as the sole carbon source. In 56 (52%) of 107 cultures, isolates with rough lipopolysaccharide emerged, and in 20 (19%) of 104 nonmucoid cultures, mucoid isolates were recovered. Strains with rough lipopolysaccharide also were sensitive to the bactericidal effect of normal human serum. Under conditions of suboptimal nutrition in vitro, isolates of P. aeruginosa emerged that produced rough lipopolysaccharide and were mucoid, typical of many isolates from cystic fibrosis patients. This peculiar phenotype may arise as a consequence of nutritional limitation within the cystic fibrosis respiratory tract rather than from features unique to these strains of bacteria. PMID- 2107199 TI - Serological response in Enterococcus faecalis endocarditis determined by enzyme linked immunosorbent assay. AB - Enterococcus (Streptococcus) faecalis expresses three species-specific surface protein antigens of molecular weights 73,000, 40,000, and 37,000. On Western blotting (immunoblotting), they were detected strongly by immunoglobulin G (IgG) in sera from patients with E. faecalis endocarditis, but not in sera from patients with other E. faecalis infections or with endocarditis due to other streptococci. We developed an enzyme-linked immunosorbent assay system to measure IgG, IgM, and IgA levels to these antigens and evaluated its potential as a serodiagnostic test for E. faecalis endocarditis. The test correctly diagnosed E. faecalis endocarditis in 15 of 16 cases. Of 10 cases of endocarditis due to other streptococci and 10 E. faecalis infections other than endocarditis, 9 and 8, respectively, gave negative results. The test should prove particularly useful in culture-negative cases, for which choice of appropriate antibiotic therapy for E. faecalis endocarditis is vital. PMID- 2107200 TI - Cytopathic astrovirus isolated from porcine acute gastroenteritis in an established cell line derived from porcine embryonic kidney. AB - A cytopathic astrovirus was isolated from pigs with acute diarrhea in an established cell line that was derived from porcine embryonic kidneys with the aid of trypsin. The virus showed a distinct cytopathic effect characterized by an enlargement of cells and the appearance of fine granules in the cytoplasm. Porcine astrovirus was shown to have an RNA genome, as determined by the effect of 5-iodo-2'-deoxyuridine on its replication, and five polypeptides with molecular masses of 13,000, 30,000, 31,000, 36,000, and 39,000 daltons; and it was shown to be stable to lipid solvents and heating at 50 degrees C for 30 min but somewhat labile to acid (pH 3.0). The buoyant density of the isolate determined in CsCl was 1.35 g/ml. Seroconversion to the virus was evident in the paired serum specimens obtained from pigs with diarrhea that were housed at the farm where the disease occurred. The neutralization test on serum specimens collected randomly from 128 adult pigs of eight herds revealed that 50 of the serum specimens were positive for antibody to porcine astrovirus, although there was considerable variation in the prevalence among herds, ranging from 0 to 83%. Hysterectomy-produced, colostrum-deprived, 4-day-old pigs developed mild diarrhea after oral exposure to porcine astrovirus propagated in the cell culture; and the virus was isolated again from diarrheal stool specimens. PMID- 2107201 TI - Identification of Bacillus anthracis by using monoclonal antibody to cell wall galactose-N-acetylglucosamine polysaccharide. AB - Guanidine extracts of crude Bacillus anthracis cell wall were used to vaccinate BALB/c mice and to develop monoclonal antibody (MAb) to vegetative cell surface antigens. Two hybridomas selected during this study produced immunoglobulin M immunoglobulins, which appear to be directed to an epitope associated with the galactose-N-acetyl-D-glucosamine polysaccharide. Both demonstrated specificity in their binding to purified B. anthracis cell wall, o-stearoyl-polysaccharide conjugates, and intact, nonencapsulated vegetative cells. The interaction of the MAbs with purified polysaccharide was inhibited by 0.5 M galactose and lactose but not by N-acetylglucosamine, glutamate, glycine, or glycerol. Inhibition by glucose or sucrose was approximately 75% of that seen with galactose. Electron microscopy showed that both MAbs interacted with the cell wall of vegetative cells as well as with the cortex of spores. Neither MAb reacted with encapsulated vegetative cells, such as those from infected guinea pigs, nor did they react with intact spores. After conjugation to fluorescein isothiocyanate, the MAbs stained intensely all B. anthracis strains tested, whereas with two exceptions, none of the strains of 20 other Bacillus spp. was stained. The exceptions, strains of Bacillus cereus, could be differentiated from B. anthracis by being beta-hemolytic on blood agar. PMID- 2107202 TI - Performance and cost-effectiveness of a dual rapid assay system for screening and confirmation of human immunodeficiency virus type 1 seropositivity. AB - Recent studies have shown that rapid, instrument-free assays for the detection of antibody to human immunodeficiency virus (HIV) can be as sensitive and specific as enzyme-linked immunosorbent assay (ELISA) for screening of donated blood in developing countries. Currently, however, specimens which test positive on a screening assay must still be confirmed by Western blot (immunoblot), a method which is not feasible in most developing-country laboratories. We examined whether a testing hierarchy which utilizes neither conventional ELISA nor Western blot can be reliably used for screening and confirmation of HIV infection in a high-risk population. In a retrospective analysis of 3,878 specimens which were screened for antibody to HIV in Kinshasa, Zaire, we observed that a testing hierarchy consisting of duplicate HIVCHEK screening assays followed by duplicate Serodia-HIV confirmatory assays resulted in correct confirmation of all ELISA- and Western blot-positive specimens. We conclude that such a testing hierarchy can produce highly accurate results for identification of positive specimens in routine HIV testing and provides a practical alternative to conventional methods of HIV screening and confirmation. PMID- 2107203 TI - Detection of Entamoeba histolytica immunoglobulins G and M to plasma membrane antigen by enzyme-linked immunosorbent assay. AB - Sixty-one serum specimens from 22 patients with clinically diagnosed amoebic liver abscess (ALA), 10 hospitalized patients with a variety of diseases other than amoebiasis, 12 normal healthy controls, and 17 subjects from an amoebiasis endemic area were assayed by enzyme-linked immunosorbent assay (ELISA). The plasma membrane fraction of axenic cultures of Entamoeba histolytica HK9 separated from other subcellular fractions by differential centrifugation was used as the antigen to detect specific immunoglobulin G (IgG) and IgM antibodies. Using a single serum dilution of 1/100 and optical densities at 492 nm of 0.200 and 0.250 as the cutoff values for the IgM and IgG ELISAs, their respective sensitivities in 22 ALA patients were 91% (20 of 22) and 95% (21 of 22). In 22 patients (10 hospitalized and 12 normal healthy controls), the specificities of the IgM and IgG ELISAs were 95% (21 of 22) and 91% (20 of 22), respectively. All five asymptomatic carriers of pathogenic E. histolytica were seropositive by the IgG ELISA and the amoebic gel diffusion test (AGDT). The AGDT was positive for three of six culture-negative controls, while the IgG ELISA was positive for all six. For six asymptomatic carriers of nonpathogenic zymodemes, the AGDT was positive for two, and the IgG ELISA was positive for three. There was an excellent correlation (r = 0.96) between the IgG ELISA and the AGDT. Only one of six culture-negative controls, none of the asymptomatic carriers of pathogenic E. histolytica, and one of six carriers of nonpathogenic E. histolytica were seropositive by the IgM ELISA, thus highlighting the specificity of the IgM ELISA in the diagnosis of ALA. It is believed that the use of plasma membrane fractions has improved the diagnostic potential of the IgM ELISA. PMID- 2107204 TI - Serum antibody response to Listeria monocytogenes, listerial excretion, and clinical characteristics in experimentally infected goats. AB - We induced an experimental listeriosis in five goats by oral inoculation of Listeria monocytogenes serovar 1/2a. The resulting generalized bacteremia was reflected by systemic illness in four of the five animals inoculated and by excretion of L. monocytogenes in milk by all five animals. By using an enzyme immunoassay, we recorded a markedly enhanced immunoglobulin G (IgG) antibody response in the two youngest and most seriously ill test animals. In these, the elimination of L. monocytogenes from the gastrointestinal tract occurred simultaneously with the development of the highest antibody levels at 14 to 15 days postinoculation. In the case of the oldest test animal, a preexisting, persistent IgG antibody response was recorded which was associated with the total absence of clinical symptoms and the shortest observed fecal carriage of L. monocytogenes, lasting for only 3 days. Two animals remained practically seronegative, and an IgM antibody response was not recorded for any of the animals. The findings suggest that an association exists between the humoral immune defense against Listeria infections, the clinical course of the infection, and the elimination of the Listeria organisms from the gastrointestinal tract. PMID- 2107205 TI - Enzyme-linked immunosorbent assay for distinguishing serological responses of lepromatous and tuberculoid leprosies to the 29/33-kilodalton doublet and 64 kilodalton antigens of Mycobacterium tuberculosis. AB - Immunoblot assays for the antibodies to Mycobacterium tuberculosis sonic extracts showed that all serum specimens of 40 lepromatous and of 28 tuberculoid leprosy patients reacted in a significant manner to 29/33-kilodalton (kDa) doublet and 64 kDa antigens, respectively. By using an enzyme-linked immunosorbent assay, we observed a significantly high immunoglobulin G antibody titer to the purified M. tuberculosis 29/33-kDa doublet and 64-kDa antigens in lepromatous and tuberculoid leprosy patients, respectively, as compared with normal subjects and tuberculosis patients. This enzyme-linked immunosorbent assay serology may be useful for distinguishing two polar types of leprosy and for diagnosing leprosy in general. PMID- 2107206 TI - Role of thyroid hormones in apolipoprotein A-I gene expression in rat liver. AB - To study the regulation of hepatic apo A-I gene expression, we measured synthesis and abundance of cellular apo A-I mRNA and its nuclear precursors in livers of hypothyroid and hyperthyroid rats. In hypothyroid animals, both synthesis and abundance of apo A-I mRNA was reduced to half of control values. After injection of a receptor-saturating dose of triiodothyronine into euthyroid rats, apo A-I gene transcription increased at 20 min, reached a maximum of 179% of control (P less than 0.01) at 3.5 h, and remained elevated for up to 48 h. The abundance of nuclear and total cellular apo A-I mRNA increased at 1 and 2 h, respectively, and exceeded the levels expected from enhanced transcription more than two fold at 24 h after hormone injection. Upon chronic administration of thyroid hormones, levels of nuclear and cytoplasmic apo A-I mRNA remained elevated but transcription of the apo A-I gene fell to 42% of control (P less than 0.01). Thus, thyroid hormones rapidly stimulate apo A-I gene transcription. Posttranscriptional events leading to increased stability of nuclear apo A-I RNA precursors become the principal mechanism for enhanced gene expression in chronic hyperthyroidism and may cause feedback inhibition of apo A-I gene transcription. Our results furthermore imply that the majority of hepatic nuclear apo A-I RNA precursors are degraded in euthyroid animals. PMID- 2107207 TI - Neutrophil elastase and cathepsin G stimulate secretion from cultured bovine airway gland serous cells. AB - To investigate the hypothesis that neutrophil proteases stimulate airway gland secretion, we studied the effect of human cathepsin G and elastase on secretion of 35S-labeled macromolecules from cultured bovine airway gland serous cells. Both proteases stimulated secretion in a concentration-dependent fashion with a threshold of greater than or equal to 10(-10) M. Elastase was more potent than cathepsin G, causing a maximal secretory response of 1,810 +/- 60% over baseline at 10(-8) M. The maximal response to cathepsin G (1,810 +/- 70% over baseline at 10(-7) M) was similar to the maximal response to elastase. These responses were greater than 10-fold larger than the response to other agonists such as histamine. Protease-induced secretion was noncytotoxic and required catalytically active enzymes. The predominant sulfated macromolecule released by proteases was chondroitin sulfate proteoglycan. Immunocytochemical staining demonstrated chondroitin sulfate in cytoplasmic granules and decreased granular staining after stimulation of cells with elastase. The neutrophil proteases also degraded the proteoglycan released from serous cells. Cathepsin G and elastase in supernatant obtained by degranulation of human peripheral neutrophils also caused a secretory response. Thus, neutrophil proteases stimulate airway gland serous cell secretion of chondroitin sulfate proteoglycan and degrade the secreted product. These findings suggest a potential role for neutrophil proteases in the pathogenesis of increased and abnormal submucosal gland secretions in diseases associated with inflammation and neutrophil infiltration of the airways. PMID- 2107208 TI - In vitro responses to Leishmania antigens by lymphocytes from patients with leishmaniasis or Chagas' disease. AB - T cell responses are correlated with recovery from and resistance to leishmaniasis. Antigens of Leishmania chagasi were evaluated by determining their ability to elicit in vitro proliferation and cytokine production in peripheral blood lymphocytes and in T cell lines and clones from patients with histories of leishmaniasis or Chagas' disease. Antigens tested were selected by their reactivity with patient antibodies. Several of the antigens induced proliferative responses in peripheral blood lymphocytes from patients recovered from visceral or cutaneous leishmaniasis or with chronic Chagas' disease. Two purified glycoproteins, 30 and 42 kD, were consistently among the most effective in eliciting high proliferative responses and IL-2 production. Lymphocytes from a recovered visceral leishmaniasis patient were used to produce T cell lines against either the 30- or 42-kD antigen. Each of the lines responded to both of these antigens as well as to crude leishmania lysate. CD4+ T cell clones specific for either or both of these antigens were also isolated from a visceral leishmaniasis patient. In contrast, rabbit antisera produced against these two antigens were not crossreactive. Both antigens were effective in inducing the production of IFN-gamma from T cell lines from both leishmaniasis and Chagas' disease patients. These studies demonstrate the potential for defining parasite antigens with broad immunostimulatory capabilities. PMID- 2107209 TI - Expression of two "immediate early" genes, Egr-1 and c-fos, in response to renal ischemia and during compensatory renal hypertrophy in mice. AB - To identify specific genetic regulatory mechanisms associated with renal ischemia, we measured the accumulation of Egr-1 and c-fos mRNAs in the mouse kidney after occlusion of the renal artery and reperfusion. At 1 h after right nephrectomy and arterial occlusion of the contralateral kidney for 10 or 30 min, Egr-1 mRNA levels were three to five times greater in these kidneys as compared with those in control animals that had sustained unilateral nephrectomy alone and were much greater than levels in the normal organ. Whether ischemia was imposed for 10 or for 30 min, renal Egr-1 mRNA contents were equivalent and remained elevated after 24 h of reperfusion subsequent to 30 min of ischemia. Although c fos mRNA also accumulated in response to ischemia and reperfusion, the pattern differed from that of Egr-1 in that c-fos mRNA content varied with the duration of ischemia and was undetectable 24 h after injury. Contralateral nephrectomy was not necessary to see the marked accumulation of Egr-1 and c-fos mRNAs with unilateral ischemia. Reflow was necessary, however, since only minimal sequence accumulation occurred by the end of the ischemic period. After left uninephrectomy alone, Egr-1 mRNA levels in the remaining kidney were maximal 30 min after surgery, but were not detectable thereafter; c-fos mRNA levels did not change after unilateral nephrectomy. Differential expression of early growth related genes implicated in transcriptional activation may influence tissue recovery after renal ischemia. PMID- 2107210 TI - Measurement of very low density and low density lipoprotein apolipoprotein (Apo) B-100 and high density lipoprotein Apo A-I production in human subjects using deuterated leucine. Effect of fasting and feeding. AB - Six normolipidemic male subjects, after an 8-h overnight fast, were given a bolus injection and then a 15-h constant intravenous infusion of [D3]L-leucine. Subjects were studied in the fasted state and on a second occasion in the fed state (small, physiological meals were given every hour for 15 h). Apolipoproteins were isolated by preparative gradient gel electrophoresis from plasma lipoproteins separated by sequential ultracentrifugation. Incorporation of [D3]L-leucine into apolipoproteins was monitored by negative ionization, gas chromatography-mass spectrometry. Production rates were determined by multiplying plasma apolipoprotein pool sizes by fractional production rates (calculated as the rate of isotopic enrichment [IE] of each protein as a fraction of IE achieved by VLDL (d less than 1.006 g/ml) apo B-100 at plateau. VLDL apo B-100 production was greater, and LDL (1.019 less than d less than 1.063 g/ml) apo B-100 production was less in the fed compared with the fasted state (9.9 +/- 1.7 vs. 6.4 +/- 1.7 mg/kg per d, P less than 0.01, and 8.9 +/- 1.2 vs. 13.1 +/- 1.2 mg/kg per d, P less than 0.05, respectively). No mean change was observed in high density lipoprotein apo A-I production. We conclude that: (a) this stable isotope, endogenous-labeling technique, for the first time allows for the in vivo measurement of apolipoprotein production in the fasted and fed state; and (b) since LDL apo B-100 production was greater than VLDL apo B-100 production in the fasted state, this study provides in vivo evidence that LDL apo B-100 can be produced independently of VLDL apo B-100 in normolipidemic subjects. PMID- 2107211 TI - Identification of the cutaneous basement membrane zone antigen and isolation of antibody in linear immunoglobulin A bullous dermatosis. AB - Linear IgA bullous dermatosis (LABD) is a rare blistering skin disease characterized by basement membrane zone deposition of IgA. This study identifies a tissue antigen detected by patient serum and then isolates the autoantibody using epidermis and protein bands blotted on nitrocellulose as immunoabsorbents. Sera from 10 patients (9 with cutaneous disease and 1 with cicatrizing conjunctivitis) were evaluated. Indirect immunofluorescence revealed an IgA anti basement membrane antibody in 6 of 10 sera with monkey esophagus substrate and 9 of 10 sera with human epidermal substrate. Immunoblotting was performed on epidermal and dermal extracts prepared from skin separated at the basement membrane zone with either sodium chloride or EDTA. Saline-separated skin expressed a 97-kD band in dermal extract alone that was recognized by 4 of 10 sera. EDTA-separated skin expressed the 97-kD band in both epidermal (4 of 10 sera) and dermal (6 of 10 sera) extract. Immunoabsorption of positive sera with epidermis purified an IgA antibody that reacted uniquely with the 97-kD band. In addition, IgA antibody bound to nitrocellulose was eluted from the 97-kD band and found to uniquely bind basement membrane zone. It is likely that the 97-kD protein identified by these techniques is responsible for basement membrane binding of IgA in LABD. PMID- 2107213 TI - Detection of lupus like anticoagulant: current laboratory practice in the United Kingdom. The Lupus Anticoagulant Working Party. AB - Various tests have been advocated for the detection of lupus like anticoagulants (LA) and related antiphospholipid antibodies, but there is no agreement on the most appropriate laboratory approach. Two hundred and fifty five of 433 hospital centres in the United Kingdom responded to a questionnaire. Many different tests were reported to be in use for screening for LA with considerable variation in plasma preparation, choice of reagent, and methodological details. Three freeze dried plasmas were subsequently assessed for the presence of LA by 183 laboratories. While 92% correctly identified a strong inhibitor and 91% a negative control, only 65% correctly identified a weak inhibitor. Pronounced variations in the suitability of commonly used reagents in the activated partial thromboplastin time test (APTT) were noted and important methodological features were identified in the kaolin clotting time, dilute thromboplastin time, and dilute Russell's viper venom time tests. It is concluded that careful plasma preparation, with avoidance of platelet contamination, use of a suitable test in addition to the APTT, and attention to methodological detail are essential for the reliable identification of LA, a clinically important inhibitor. PMID- 2107212 TI - Counterregulatory effects of interferon-gamma and endotoxin on expression of the human C4 genes. AB - Susceptibility to autoimmune disease is associated with null alleles at one of the two genetic loci encoding complement protein C4. These two genetic loci, C4A and C4B, are highly homologous in primary structure but encode proteins with different functional activities. Expression of C4A and C4B genes is regulated by IFN-gamma in human hepatoma cells and in murine fibroblasts transformed with the respective genes. In these cell lines, IFN-gamma has a significantly greater and longer-lasting effect on expression of C4A than that of C4B. In this study we examined synthesis and regulation of C4A and C4B in peripheral blood monocytes from normal, C4A-null, and C4B-null individuals. Synthesis of C4 in human peripheral blood monocytes decreases during time in culture. IFN-gamma mediates a concentration- and time-dependent increase in steady-state levels of C4 mRNA and a corresponding increase in synthesis of C4 in normal human monocytes. LPS decreases monocyte C4 expression and completely abrogates the effect of IFN-gamma on the expression of this gene. In contrast, LPS and IFN-gamma have a synergistic effect in upregulating expression of another class III MHC gene product, complement protein factor B. The effect of LPS on constitutive and IFN-gamma regulated C4 synthesis is probably not mediated via release of endogenous monokines IL-1 beta, TNF-alpha, or IL-6. Synthesis of C4, and regulation of its synthesis by IFN-gamma and LPS, are similar in normal, C4A-, and C4B-null individuals. These results demonstrate the synthesis of C4 at extrahepatic sites and tissue-specific regulation of C4 gene expression. PMID- 2107214 TI - An evaluation of the therapeutic effects and dosage equivalence of glyburide and glipizide. AB - Nineteen noninsulin-dependent diabetic patients [ten women, nine men, aged 36-80 years (mean +/- SE 56.8 +/- 2.7 years)] were randomized to receive either glyburide or glipizide for 16 weeks, in a double-blind crossover fashion. A 2 week washout period preceded each treatment period. The patients measured blood glucose concentrations 16 times weekly using Chemstrip-bG. The medication dosages were titrated to achieve fasting blood glucose concentrations of less than or equal to 6.2 mM and preprandial and postprandial concentrations of less than or equal to 9.0 mM, or to a total daily dose of 20 mg for glyburide and 40 mg for glipizide. Glyburide therapy resulted in a significant decline in fasting, preprandial, postprandial and bedtime blood glucose levels, while glipizide treatment led to a significant lowering of postprandial and bedtime blood glucose. Furthermore, fasting, preprandial and postprandial blood glucose concentrations were significantly lower during glyburide as compared to glipizide treatment phase. Glycosylated hemoglobin levels were decreased only with glyburide. Serum C-peptide and insulin concentrations were not altered over the entire study. The mean final daily dose of glyburide (15.4 +/- 1.6 mg) was markedly lower than that of glipizide (29.7 +/- 3.1 mg). Thus, in this patient population, glyburide was twice as potent on a weight basis than glipizide. PMID- 2107215 TI - Effect of short-term beta blockade on serum lipid levels and on the interaction of LDL with human arterial proteoglycans. AB - In view of conflicting evidence suggesting that beta-blockers have an anti atherogenic effect as well as induce a potentially atherogenic lipoprotein profile, the effects of a short term beta-blockade on serum lipoproteins were studied in 39 healthy volunteers. Because the interaction of LDL with arterial proteoglycans appears to play a role in lipoprotein accumulation during atherogenesis, the effects of metoprolol and atenolol on low density lipoprotein interaction with human aortic proteoglycans were included in the study. We could confirm that the beta-blockers caused a decrease in HDL cholesterol and an increase in triglycerides, both potentially undesirable effects. In addition, however they induced a significant decrease in the in vitro LDL affinity for arterial proteoglycans. Since there appears to be a strong association between LDL reactivity with proteoglycans and risk for myocardial infarction, this effect of the beta-blockers may be an anti-atherogenic effect which overrides other effects on the lipoprotein pattern. PMID- 2107216 TI - Effects of protein deprivation on pyramidal cells of the visual cortex in rats of three age groups. AB - The effect of protein deprivation on rapid Golgi impregnated pyramidal neurons in layers II/III and V of the rat visual cortex was studied at 30, 90, and 220 days of age using morphometric methods. In order to mimic human under-nutrition female rats were adapted to either an 8% or control 25% casein diet 5 weeks prior to conception and maintained on these diets during gestation and lactation. The pups were then weaned and maintained on their respective diets. The undernourished rats showed a significant decrease in brain weight only at 90 days, indicating that the protein deprivation had a mild effect on brain development. Correspondingly, the number of significant histological differences between the two diet groups were least at 30 and 220 days of age. The effect of the diet was greater on layer V than on layer II/III pyramids. At 30 days of age the effect of the diet was different on the pyramids of these two cell layers, at 90 days there was a mixture of similar and dissimilar effects, and at 220 days the pyramids of these two cell layers showed only minor differences between the two diet groups. Analysis of age-related changes indicated that the effect of the diet was different on layer II/III pyramids compared to layer V pyramidal cells. These different effects apparently accounted for the progression from a dissimilar effect of the diet at 30 days on the pyramids of the two cell layers to only minor differences between them at 220 days. Further analysis of these age-related changes shows that two prominent effects of protein deprivation are for age related changes to occur in undernourished rats but not in controls and for age related changes to be out-of-phase with each other in the two diet groups. From these findings, and a review of similar studies in the literature, we propose that these mechanisms are a prominent effect of undernutrition in the post weaning period and help account for the unexpected increases in morphometric measurements noted in undernourished rats in this and other studies. PMID- 2107217 TI - Characterization and measurement of immunoglobulins in the grey seal (Halichoerus grypus). AB - Immunoglobulin concentrations were measured in the serum and colostrum of adult and pup Grey seals from North Rona in the outer Hebrides and the Isle of May in the Firth of Forth. IgG was shown to be the main immunoglobulin and two subclasses were identified. Serum immunoglobulin content was low in the week-old pups and increased up to 5 weeks, although it remained substantially lower than in the adults. Colostral immunoglobulins were high and cannot explain the low values in the pup serum. It is considered that the increased opportunistic infections seen in Grey seal pups may be related to this low immunoglobulin status. PMID- 2107218 TI - Genetic counseling in segmental neurofibromatosis. AB - We report two patients with segmental neurofibromatosis and review the literature with regard to possible hereditary transmission of this disorder. Patients that meet strict criteria for the diagnosis of segmental neurofibromatosis seem to have a low probability of transmitting the disease. We emphasize the importance of establishing and strictly adhering to a set of diagnostic criteria and of obtaining a comprehensive family history when reporting cases of segmental neurofibromatosis. PMID- 2107219 TI - The effect of intralesional interferon gamma on basal cell carcinomas. AB - This open label study evaluated the effect of nine intralesional injections of two different doses of interferon gamma on basal cell carcinomas in 29 patients. One group of 15 patients received interferon gamma, 0.01 mg (20,000 IU), intralesionally three times a week for 3 weeks. Fourteen patients received interferon gamma, 0.05 mg (100,000 IU), intralesionally in the same dosage schedule. Excisional biopsy specimens 12 weeks after therapy showed no evidence of tumor remaining in 7 of 14 patients (50%) treated with the higher dose of interferon gamma, whereas only 1 of 15 patients (7%) treated with low-dose interferon gamma was cured according to histologic criteria (p = 0.025). Seventy six percent of patients reported at least one adverse reaction, but most were considered mild by the patient and the investigator. PMID- 2107220 TI - Progressive facial hemiatrophy (Parry-Romberg syndrome) and borreliosis. PMID- 2107221 TI - Application of world class service to world class nursing. AB - U.S. nursing is in trouble. These numerous and multidimensional troubles include general job dissatisfaction, low morale, a severe nurse shortage, a high turnover rate, and a rapid cost increase. A brief study of the healthcare industry in other industrialized nations revealed that those nations do not face the same problems or at least their problems are not as severe. More specifically, the Japanese nursing industry has no shortage. This article addresses some of the United State's nursing problems and presents some solutions from World Class Service concepts to those problems. The concepts of flexible scheduling, simplification of processes and standardization, on-the-job training, employee involvement, and team building are discussed in the context of World Class Nursing. Finally, the importance of regarding all of the above mentioned concepts as an integral part of healthcare improvement efforts is emphasized. PMID- 2107222 TI - Comparison of nurses' self-directed learning activities. AB - This study compares the self-directed learning (SDL) practices of baccalaureate (40) and master's (40) nurses. Using a personal interview format, nurses were queried as to the number and nature of their SDL projects. Based on the study data, nurses spend a greater portion of their SDL time on professional area content. Respondents indicated they spend an average of 313 hours per year on independent learning projects with 217 of those hours on professional topics. Master's-prepared nurses spend more time per year (398 hours) and slightly more time on professional content (71%) compared to the time baccalaureate-prepared nurses spend per year (230 hours) on professional content (67%). Implications for nursing education are identified with respect to learner motivation and accessibility of materials. PMID- 2107223 TI - Marketing a continuing education course for healthcare managers. AB - The purpose of this article was to elicit from the relevant literature the important considerations to make when planning to market continuing education (CE) within hospitals. References on marketing from both institutions of higher education and hospitals were reviewed. Based on this review, a strategic marketing plan was developed and initially implemented in the hospital. A 1-day course for healthcare managers, entitled "Successful Writing of Proposals and Reports," was offered twice and tested, using the steps outlined in the strategic marketing plan. The plan proved to be most beneficial in systematically guiding our first attempts at marketing CE to hospitals and other healthcare facilities. From this plan, efforts are currently being made to further develop curricula and determine other programs that might be marketable to these same target groups. In addition, closer links with nearby educational institutions or affiliated hospitals are being pursued to support and maintain our ongoing marketing endeavors. PMID- 2107224 TI - Transfer of continuing education to practice: testing an evaluation model. AB - A continuing education (CE) program is successful only to the extent that a recommended practice or behavior is implemented. The social system in which the nurse practices and the nurse's own receptiveness to change also influence the application of new knowledge. PMID- 2107225 TI - Personal and work-milieu resources as variables associated with role mastery in the novice nurse. AB - The purpose of this study was to explore the relative contribution of eight independent variables in explaining novices' perceived variation in role mastery 3 months following their appointment. The study sample included 75 novice graduate nurses in a large tertiary teaching hospital. A correlational design using the multivariate procedure of step-wise multiple regression was used. On day one of orientation, the Schwerian Six-Dimensional Scale of Nursing Performance was administered to the novices, their preceptors, and head nurses. To obtain a measure of the nursing unit's collective expertise, its job satisfaction, and its role socialization, nurse educators rated their units using the Nursing Practice Group Role Mastery Assessment Scale. Participation in bicultural training was documented by attendance. Three months later, the novices were posttested using the Schwerian Scale as the criterion variable. Of the eight potential explanatory variables, only four entered the regression equation, explaining 40% of the variance (p less than .05). These were: entry-level role mastery, the nursing unit's collective expertise, its job satisfaction, and its role socialization. Interestingly, the head nurse's role mastery, and the three interventions used to address role transition problems were not predictors. Also, specific competency weaknesses in novices paralleled their experienced peers in the areas of assessing priorities, written communication, and skills salient to discharge planning. PMID- 2107226 TI - Education in nursing diagnosis: evaluating clinical outcomes. AB - This article describes the development, implementation, and evaluation of an educational program to update the knowledge and skills of nurses in the use of the nursing process and nursing diagnoses. Results 1 year later suggest improvement in participants' knowledge of the phases of the nursing process. Chart audits demonstrated this knowledge was more specifically applied to improved documentation of nursing diagnoses. PMID- 2107227 TI - Wanted: nurses with critical thinking skills. AB - Knowing how to think, apply, analyze, synthesize, and evaluate are crucial skills for nursing professionals. Development of critical thinking skills requires educational involvement beyond the level of basic preparation. The diffusion of nursing knowledge afforded by continuing education in nursing makes it the perfect milieu for the enhancement and continuous development of critical thinking skills. PMID- 2107228 TI - Brief: management and leadership learning needs in a community setting--education and practice implications. PMID- 2107229 TI - Comparison of lactoferrin content in colostrum between different cattle breeds. AB - Lactoferrin content of colostrum obtained from cows within 24 h after parturition was measured using a single radial immunodiffusion test and was compared among cows of two dairy breeds (Holstein-Friesian, Jersey) and two beef breeds (Japanese Black and Japanese Brown). Average lactoferrin content in colostrum of dairy breeds was 2 mg/ml and in colostrum of beef breeds was .5 mg/ml. Lactoferrin content of colostrum due to lactation number was also different among breeds. In dairy breeds, multiparous cows had lactoferrin content two to three times higher than that of primiparous cows; beef breeds showed no obvious differences between lactation years. Lactoferrin content also varied considerably within breed. In beef breeds, half the cows had values of nearly zero. Transferrin content in colostrum was fairly constant (.9 mg/ml) and was not as variable among and within breeds. There was no correlation between lactoferrin and transferrin contents in colostrum. Examination of cows lacking lactoferrin suggested that transferrin plays an important role as an iron carrier from a cow to her newborn calf. PMID- 2107230 TI - Dietary fat and ruminally protected amino acids for high producing dairy cows. AB - Eight early lactation Holstein cows, used in a replicated 4 x 4 Latin square design, were fed the following diets: control; control plus ruminally protected amino acids (15 g methionine and 20 g lysine); control plus added fat (.32 kg 60:40 animal and vegetable blend and .36 kg of Ca salts of fatty acids); control plus ruminally protected amino acids plus added fat. The objective was to examine the effect of ruminally protected forms of lysine and methionine and dietary fat on milk yield and composition. Cows were fed for ad libitum consumption of total mixed diets consisting of 50% forage and 50% concentrate on a DM basis. Added fat increased milk, fat, and 4% FCM yield but decreased milk protein percentage. Ruminally protected amino acids increased milk protein percentage. The combined effect of fat and ruminally protected acids increased milk fat percentage and yield more than the sole addition of either supplement. Added fat increased the percentage and yield of long-chain fatty acids in milk. Plasma free fatty acids were also increased by fat addition. Adding ruminally protected amino acids to fat-supplemented diets may help alleviate the milk protein depression found with added fat. PMID- 2107231 TI - CO2 laser application to the mineralized dental tissues--the possibility of iatrogenic sequelae. AB - From the many types of laser that are available commercially, the CO2 laser is presently thought to have the greatest potential for use in dentistry. An outline of the generation of emitted radiation from such a laser is given together with a review of work previously carried out and reported in the literature regarding application to the teeth. The main points of interest are the effects of radiation on the enamel and dentine, but concern is felt towards the possible iatrogenic damage of thermal origin that may occur within the pulp following irradiation of the dental tissues. PMID- 2107232 TI - The future of water fluoridation. AB - Recently, questions have been raised about the possible reduced effectiveness and cost-effectiveness of water fluoridation in the prevention of dental caries in developed countries. The increase in environmental fluorides since water fluoridation was first introduced in 1945 (particularly from fluoride toothpastes, mouthrinses, and from foods and drinks) generally provided the basis for these questions. A related phenomenon which might decrease the efficiency of water fluoridation is the reduced caries levels in many developed countries. It has also been suggested that excessive fluoride intake, especially in fluoridated communities where there is widespread use of fluoride toothpastes, is likely to manifest itself in an increased dental fluorosis prevalence. In this paper, recent data from Ireland which are similar to those recorded in many developed countries are used to answer these questions in part. It is concluded that water fluoridation continues to be an effective and cost-effective strategy for caries prevention in areas where the overall caries level has declined and where the cost of water fluoridation implementation has increased. Also, there is no evidence of excessive fluoride intake in fluoridated communities where fluoride toothpastes are widely used. PMID- 2107233 TI - Feasibility of the combined use of fluorides. AB - An increase in the number of methods of fluoride administration over and above traditional modes, while offering new caries-preventive possibilities, has also created problems. These cannot be solved by the purely scientific, objective approach, since emotional resistance to fluoride has increased in some countries in parallel to environmental pollution. In most of the highly developed countries, the decrease of caries prevalence has dramatically lowered the number of children in need of concentrated preventive programs. On the other hand, dental awareness and multiple sources of fluoride have increased the risk of chronic fluoride overdosage. Means to avoid the latter problem are discussed. In addition to community-delivered fluoridation programs, individual counseling and "tailor-made" preventive measures are of increasing importance. PMID- 2107234 TI - Plasma fibronectin concentrations in blood products. AB - Plasma fibronectin is an important opsonic protein of the mononuclear phagocyte system (MPS). In this study, plasma fibronectin concentrations were measured in stored and fresh whole blood, fresh frozen plasma and AGH cryoprecipitate. Stored whole blood had the lowest concentrations (151 +/- 50 mg/l). The concentrations in fresh whole blood plasma (227 +/- 66 mg/l) and fresh frozen plasma (224 +/- 78 mg/l) were similar but significantly higher than in stored whole blood (p less than 0.05). In contrast, AHG cryoprecipitate had the highest fibronectin concentrations (3249 +/- 502 mg/l) (p less than 0.001). In correcting fibronectin deficiency the best results can thus be expected from an infusion of cryoprecipitate, but fresh whole blood and fresh frozen plasma may also increase depressed fibronectin levels. PMID- 2107235 TI - The rate of gastrointestinal bleeding in a general ICU population: a retrospective study. AB - We retrospectively reviewed 298 charts in order to evaluate the efficiency of a protocol used to prevent gastrointestinal bleeding among ICU patients. The protocol included the use of an antacid (186 patients), iv administration of cimetidine (66 patients), or both drugs when the combination was needed because of a persistently low gastric pH after antacid (28 cases). In 18 cases the implementation of this protocol was stopped when enteral feeding through a nasogastric tube was started. All four groups were homogenous for average age and the presence of risk factors at admission as well as at the time of bleeding. Nevertheless the percentage of gastric bleeding during ICU stay (coffee-ground vomitus haematemesis and/or melaena) widely varied: 5% for the antacid group; 15% in the cimetidine group; 25% in the "both" group and 56% in the "enteral" group. Possible explanations for these differences are discussed. The results support the use of treatment protocols in order to prevent gastrointestinal bleeding in patients with risk factors who are admitted to ICU. PMID- 2107236 TI - The Thrombolysis in Myocardial Infarction (TIMI) Trial phase II: additional information and perspectives. AB - Given the many thrombolytic agents and the number of ways in which they can be combined with mechanical revascularization, the treatment of acute myocardial infarction has been the subject of active study and lively debate, which are likely to continue for some time. Several studies, including TIMI IIA (2,3,10,22), have suggested that immediate catheterization and angioplasty offer no clinical benefit and have a greater complication rate than a more delayed invasive strategy, but TIMI II (1) and SWIFT (16) trials have suggested that an even more conservative strategy of reserving catheterization and coronary angioplasty after thrombolytic therapy for patients with recurrent spontaneous or exercise-induced ischemia may be the most desirable approach for the majority of patients similar to those entered into these trials. PMID- 2107237 TI - Improved infarct-related arterial patency after high dose, weight-adjusted, rapid infusion of tissue-type plasminogen activator in myocardial infarction: results of a multicenter randomized trial of two dosage regimens. AB - To determine whether a weight-adjusted high dose (2 mg/kg body weight over 3 h) rapid infusion of recombinant tissue-type plasminogen activator (rt-PA) was more efficacious than a weight-adjusted standard dose (1.25 mg/kg over 3 h) in achieving reperfusion in the setting of acute myocardial infarction, 175 patients were entered into a randomized multicenter trial. Eighty-four patients were entered into the high dose group, receiving 1.2 mg/kg (10% given as a bolus injection) over 1 h, followed by 0.8 mg/kg over the next 2 h. Ninety-one patients were given 0.75 mg/kg (10% given as a bolus injection) in 1 h, followed by 0.5 mg/kg administered over the next 2 h. The median dose in the group that received 2 mg/kg dose was 145 mg, compared with 100 mg in the group that received 1.25 mg/kg. The 90 min patency rate in the group that received 2 mg/kg was 84% compared with 70% in the group that received 1.25 mg/kg (p = 0.003). Sixty-four percent of the patients in each group underwent coronary angioplasty at the time of cardiac catheterization. The infarct-related artery patency rate at the end of catheterization was 91% in the group that received 2 mg/kg compared with 83% in the group that received 1.25 mg/kg (p = 0.08). Among patients with a patent infarct-related coronary artery after catheterization, the 6 month mortality rate in the group that received 2 mg/kg was 2.9% compared with 9.8% in the group that received 1.25 mg/kg (p = 0.15). The bleeding complication rate in the two groups was similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107238 TI - Ultrathrombolysis. PMID- 2107239 TI - Should thrombolytic therapy be administered in the mobile intensive care unit in patients with evolving myocardial infarction? A pilot study. AB - The growing recognition of the importance of early thrombolysis in evolving myocardial infarction was the basis for the present study, which evaluated the effectiveness, feasibility and safety of prehospital thrombolytic therapy. In a relatively small study, 118 patients were allocated to receive either prehospital treatment with recombinant tissue-type plasminogen activator (rt-PA) in the mobile intensive care unit (group A, 74 patients) or hospital treatment (group B, 44 patients). A total of 120 mg of rt-PA was infused over a period of 6 h. All patients were fully heparinized and underwent radionuclide left ventriculography and coronary angiography during hospitalization. Although group A was treated significantly earlier than group B after onset of symptoms (94 +/- 36 versus 137 +/- 45 min, respectively; p less than 0.001), no significant differences were observed between the groups in 1) extent of myocardial necrosis, 2) global left ventricular ejection fraction at discharge, 3) patency of infarct-related artery, 4) length of hospital stay, and 5) mortality at 60 days. However, a trend to a lower incidence of congestive heart failure at hospital discharge was observed in the prehospital-treated compared with the hospital-treated group (7% versus 16%, respectively; p = NS). No major complications occurred during transportation. It is concluded that myocardial infarction can be accurately diagnosed and thrombolytic therapy initiated relatively safely during the prehospital phase by the mobile intensive care team, thus instituting a beneficial clinical trend in favor of prehospital thrombolysis. PMID- 2107240 TI - Pharmacokinetics and pharmacodynamics of terfenadine and chlorpheniramine in the elderly. AB - In a double-blind, randomized, crossover study, the H1-receptor antagonists, terfenadine and chlorpheniramine, were investigated in eight healthy, fasting female subjects, aged 67.8 +/- SD 0.8 years, who ingested single doses of terfenadine, 1 mg/kg (mean dose, 69.6 +/- 11.2 mg), and chlorpheniramine, 0.12 mg/kg (mean dose, 8.4 +/- 1.3 mg). The mean serum-elimination half-life of terfenadine metabolite I was 8.7 +/- 3.7 hours. After terfenadine ingestion, significant wheal suppression occurred from 2 to 24 hours compared to predose wheal size, with maximum wheal suppression, 42 +/- 13% to 60 +/- 16% from 2 to 12 hours. Significant flare suppression occurred from 2 to 24 hours, with maximum flare suppression, 75 +/- 15% to 78 +/- 13% from 4 to 8 hours. The mean serum elimination half-life of chlorpheniramine was 22.6 +/- 11.0 hours. After chlorpheniramine ingestion, significant wheal suppression occurred from 1 to 10 hours, inclusive, compared to predose wheal size, with maximum wheal suppression, 36 +/- 11% to 37 +/- 11% from 5 to 6 hours. Significant flare suppression occurred from 1 to 12 hours, with maximum flare suppression of 43 +/- 14% to 46 +/- 19% at 2, 5, and 6 hours (p less than 0.01). Adverse effects, chiefly sedation, occurred in five of eight patients after receiving terfenadine, and in all eight patients after receiving chlorpheniramine; but, since no placebo control was administered, these adverse effects could not be definitely attributed to H1-receptor-antagonist ingestion. PMID- 2107241 TI - Comparison of the efficacy and side effects of aqueous steroid nasal spray (budesonide) and allergen-injection therapy (Pollinex-R) in the treatment of seasonal allergic rhinoconjunctivitis. AB - The efficacy and side effects of two approaches to the treatment of ragweed pollen-induced rhinoconjunctivitis were compared in a double-blind, parallel group trial. Sixty ragweed-sensitive adults were randomized either to a course of four Pollinex-R hyposensitization injections during the 6 weeks before the ragweed-pollen season, or to budesonide aqueous nasal steroid spray, 400 micrograms daily, throughout the season. A double-dummy technique was used to achieve blinding. During the ragweed-pollen season, troublesome nasal symptoms were treated with terfenadine, 60 mg, when treatment was needed, up to 240 mg daily, and eye symptoms were treated with naphazoline eye drops, when treatment was needed, up to four times daily. Every day, subjects recorded the severity of nasal and eye symptoms and medication use in a diary. Fourteen of the subjects receiving Pollinex-R were unable to complete the course of injections because of systemic or large local reactions. Eight subjects withdrew during the pollen season because of severe rhinitis; all subjects had received Pollinex-R. Subjects in the budesonide-treated group had minimal nasal symptoms and used very little terfenadine, compared with subjects in the Pollinex-R-treated group (p less than 0.0001). Eye symptoms and eye drop use were similar in the two treatment groups. No clinically important side effects were reported by the subjects receiving budesonide. The results of this study suggest that aqueous budesonide nasal spray is markedly more effective than Pollinex-R in controlling symptoms of seasonal rhinitis while the side effects and inconvenience of immunotherapy are avoided. PMID- 2107242 TI - A double-blind, randomized study of sodium cromoglycate versus placebo in patients with cystic fibrosis and bronchial hyperreactivity. AB - To evaluate the effects of sodium cromoglycate (SCG) on patients with cystic fibrosis (CF) and with bronchial hyperreactivity, a long-term, double-blind, placebo-controlled, crossover study was performed. Fourteen patients with CF and without asthma (aged 7 to 29 years) and with bronchial hyperreactivity entered the study. Each patient received 8 weeks of 1% SCG nebulizer solution three to four times daily and 8 weeks of placebo. Seven patients received the treatment in the order SCG/placebo and seven patients in the reverse order. Evaluation of SCG effect was performed every 4 to 8 weeks by (1) clinical assessment of symptoms, (2) clinician and patient/parent opinion, (3) pulmonary function tests, and (4) methacholine provocation tests. After two patients were withdrawn for lack of cooperation, the results were evaluated for treatment effect (SCG versus placebo), period effect (whether SCG was administered first or last), or combination of both. No significant difference was found for these parameters for the clinical assessment of symptoms, the patient/parent and clinician opinion, their subjective preferences, the metacholine challenges, or the pulmonary function tests. The study did not demonstrate any benefit from the use of SCG in patients with CF and with bronchial hyperreactivity and does not support the routine use of SCG in patients with CF. PMID- 2107243 TI - Clinical and serologic follow-up of four children and five adults with bird fancier's lung. AB - We report the clinical and serologic findings in four children and five adults with chronic avian hypersensitivity pneumonitis. All subjects were treated with corticosteroids and bird exposure was reduced or eliminated. After a variable period, ranging from 6 months to 10 years, their clinical and serologic findings were reassessed. In terms of symptomatology, chest findings, and pulmonary functions, all four children improved and four adults improved, whereas one adult had a progressive clinical deterioration, ultimately resulting in her death 5 years later. In terms of serologic data, precipitating antibody tended to persist, and antibody to avian antigens, as determined by ELISA, remained positive, although the titer declined. We conclude that, while serologic positivity remains, the prognosis for children and adults with chronic avian hypersensitivity pneumonitis is very good, provided that irreversible damage has not already occurred at the time of diagnosis. PMID- 2107244 TI - Adaptive response of pancreatic and intestinal function to nutritional intake in the aged. PMID- 2107245 TI - Behavioral treatment of incontinence in the long-term care setting. PMID- 2107246 TI - The impact of community care on provision of informal care to homebound elderly persons. AB - This study examined the impact of community care on informal care provided by family and friends to homebound elderly persons. Secondary analyses were conducted on data collected from clients at baseline, 9 months (N = 225), and 48 months (N = 76) after acceptance to community care and home-delivered meals programs. Analyses revealed a significant increase in the amount of formal services provided to both groups of clients at 9 months and to community care clients at 48 months. The increase was attributed to the large proportion of "new" or "supplementary" services provided by agencies. No significant decrease in the amount of service provided by informal caregivers was found. In addition, regression analyses demonstrated only a weak impact of formal service on informal care. Analysis of patterns of service provision for each client demonstrated that formal care supplemented rather than substituted for informal care significantly more often in both the 9- and 48-month samples. We conclude that formal care in general supplemented the efforts of informal caregivers, and that informal caregiving remained stable over time. PMID- 2107247 TI - [Cost-effectiveness analysis of HIV screening in pregnant women in hospitals in the Paris region]. AB - Spontaneous diffusion of HIV screening at the occasion of pregnancy has been especially rapid in France. In April-May 1988, 45% of general practitioners systematically prescribed HIV screening during premarital or prenatal consultations. Experimentation of systematic prenatal HIV screening has been performed for some time in various French maternity hospitals. On the basis of real data concerning HIV screening of more than 15,000 pregnant women between August 1987 and July 1988 in 9 Paris hospitals, a cost-effectiveness analysis has been performed. It showed that the total cost of systematic screening for women admitted to maternity hospitals for prenatal care and whose HIV status was previously unknown, was about 1.5 million French francs (about $240,000) and that 22 new cases of HIV positive were discovered. During the first five months (first period), the mean cost per pregnant woman found to be HIV positive was about 42 to 45,000 FF ($6,700-7,150). A similar calculation over the following months, gave a mean cost 4 times higher. The cost and effectiveness of a selective screening for high risk women were also estimated. In this hypothetical case, 13.6% of women would have been tested, the mean cost of discovering, at the hospital, a new HIV positive pregnant woman would have been 7,500 FF ($1,200) during the first period. The quadrupling of the mean cost of identifying an HIV positive pregnant woman by systematic hospital screening, despite a concomitant increase in prevalence in the population, can be explained only by an increase in prenatal screening prescribed by the private practitioner in ambulatory medicine before the first hospital prenatal visit. The monthly evolution of the proportion of women already screened before consultation in one of the nine maternity hospitals had increased by almost 50% between the beginning and the end of the studied period. An evaluation of a policy of HIV screening during pregnancy depends, at least in the French health care system, on the different ways the ambulatory and hospital sectors complement themselves. PMID- 2107248 TI - Pseudomonas aeruginosa revisited. PMID- 2107249 TI - Clinical predictors of infection of central venous catheters used for total parenteral nutrition. AB - To identify predictors of infection in catheters used for total parenteral nutrition (TPN), clinical and microbiological data were prospectively collected on 169 catheter systems (88 patients). Based on semiquantitative catheter cultures, infection was associated with a positive insertion site skin culture taken close to the time of catheter removal (relative risk [RR] = 4.50), especially one yielding greater than or equal to 50 colonies of an organism other than coagulase-negative staphylococci. Infection was also associated with erythema at the insertion site greater than 4 mm in diameter (RR = 2.93). In a subset of 67 catheters for which blood cultures were obtained, infection was also associated with a positive peripheral venous blood culture (RR = 5.90) and a positive central venous blood culture obtained through the catheter (RR = 5.44). Based on a logistic regression model, periodic cultures of the insertion site should be useful in evaluating subsequent fever in stable patients with indwelling central venous catheters. Another source of fever is likely if inflammation is absent and there is either no colonization or there is colonization by less than 50 colonies of coagulase-negative staphylococci at the insertion site. Conversely, the catheter should be removed and cultured semiquantitatively if the site is colonized by an organism other than coagulase negative staphylococci. We suggest that blood culture results add little to the risk estimate in these situations. PMID- 2107250 TI - Hospital reimbursement patterns among patients with surgical wound infections following open heart surgery. AB - Of the more than 200,000 patients who undergo open heart surgery annually in the United States, 2% to 10% will develop a post-operative infection related to their surgery. The economic impact of such infections on hospitals under the prospective payment system is unclear. To study the effect of such infections on hospital costs and reimbursement patterns, we compared case patients with controls of similar age, sex, urgency of surgery and type of surgery. The postoperative stay for cases was significantly longer than for matched controls (26.8 days and 8.3 days, respectively; p = .0002). The mean hospital cost for case admissions ($25,957) was twice as high as for control admissions ($12,795) (p = .0002). Cases resulted in an average net loss to the hospital of $2,344 per patient, while controls yielded an average net gain of $3,196 per patient (p = .02). We conclude that hospitals have substantial financial incentives to minimize the incidence of postoperative wound infections associated with open heart surgery. PMID- 2107251 TI - The disinfectant dilemma revisited. PMID- 2107252 TI - Purification and characterization of intraparenchymal lung lymphocytes. AB - We analyzed phenotypic and functional characteristics of intraparenchymal pulmonary lymphocytes in mice. As determined by flow cytometry, approximately 30% more T cells than B cells were found. Nearly all T cells bore the alpha beta TCR, most of which stained with either CD4+ or CD8+, although small numbers of double negative T cells were present; the CD8+/CD4+ ratio was approximately 0.37. While practically all B cells bore surface IgM, and no IgA+ cells were found, and approximately more than 80% of the plasma cells produced IgA. Approximately half of the LPS-responsive cells produced IgA. Pulmonary B cell clonal precursors specific for the autoantigen, transferrin, were present in higher frequencies than those specific for the bacterial antigens, levan and Pseudomonas aeruginosa polysaccharide type I, or those producing antibodies against OVA. These results demonstrate that a distinct population of lymphocytes is present in the lungs. PMID- 2107253 TI - Effects of six different cytokines on lymphocyte adherence to microvascular endothelium and in vivo lymphocyte migration in the rat. AB - The first step in the migration of lymphocytes out of the blood is adherence of lymphocytes to endothelial cells (EC) in the postcapillary venule. It is thought that in inflammatory reactions cytokines activate the endothelium to promote lymphocyte adherence and migration into the inflammatory site. Injection of IFN gamma, IFN-alpha/beta, and TNF-alpha into the skin of rats stimulated the migration of small peritoneal exudate lymphocytes (sPEL) into the injection site, and these cytokines mediated lymphocyte recruitment to delayed-type hypersensitivity, sites of virus injection, and in part to LPS. The effect of cytokines on lymphocyte adherence to rat microvascular EC was examined. IFN gamma, IFN-alpha/beta, IL-1, TNF-alpha, and TNF-beta increased the binding of small peritoneal exudate lymphocyte (sPEL) to EC. IFN-gamma was more effective and stimulated adherence at much lower concentrations than the other cytokines. IL-2 did not increase lymphocyte adherence. LPS strongly stimulated lymphocyte binding. Treatment of EC, but not sPEL, enhanced adhesion, and 24 h of treatment with IFN-gamma and IL-1 induced near maximal adhesion. Lymph node lymphocytes, which migrate poorly to inflammatory sites, adhered poorly to unstimulated and stimulated EC, whereas sPEL demonstrated significant spontaneous adhesion which was markedly increased by IFN-gamma, IL-1, and LPS. Spleen lymphocytes showed an intermediate pattern of adherence. Combinations of IFN-gamma and TNF-alpha were additive in stimulating sPEL-EC adhesion. Depletion of sPEL and spleen T cells by adherence to IFN-gamma stimulated EC decreased the in vivo migration of the lymphocytes to skin sites injected with IFN-gamma, IFN-alpha/beta, TNF-alpha, poly I:C, LPS, and to delayed-type hypersensitivity reactions by 50%, and significantly increased the migration of these cells to normal lymph nodes, as compared to unfractionated lymphocytes. Thus the cytokines and lymphocytes involved in migration to cutaneous inflammation in the rat stimulate lymphocyte adhesion to rat EC in vitro, and IFN-gamma stimulated EC appear to promote the selective adhesion of inflammatory site-seeking lymphocytes. PMID- 2107254 TI - Regulation of B lymphocyte responses to IL-4 and IFN-gamma by activation through Ly-6A/E molecules. AB - The Ly-6 family of cell surface molecules has previously been shown to participate in T cell activation. We show that Ly-6A/E proteins also modulated the response of normal B lymphocytes in three separate in vitro assays. First, unfractionated or small resting B cells proliferated when cultured with IFN gamma, IL-4, and an anti-Ly-6A/E mAb. Second, this anti-Ly-6A/E mAb restored B cell proliferation responses that were inhibited when coculturing the B cells in IFN-gamma, IL-4, and anti-IgM. Third, anti-Ly-6A/E specifically up-regulated the cell surface expression of its own Ag, and this response was dependent upon co stimulation with IFN-gamma. Mixing of T and B cells in culture suggested that T cells did not contribute substantially to the B cell proliferative response. Moreover, up-regulation of Ly-6A/E was observed for one B cell lymphoma, WEHI 231. Therefore, it appeared that modulation of B cell function by anti-Ly-6A/E was due to a direct effect of the mAb binding to the B cells. Taken together, these data suggest Ly-6A/E proteins are functional on B cells and may play a regulatory role in B cell activation. PMID- 2107255 TI - IL-1 induces IL-1. IV. IFN-gamma suppresses IL-1 but not lipopolysaccharide induced transcription of IL-1. AB - IL-1 induces its own gene expression in human PBMC, in cultured smooth muscle and in endothelial cells. IL-1-induced IL-1 may be part of a self-amplification or an autocrine growth factor in a variety of responses, and thus the endogenous regulation of IL-1 production likely contributes to the outcome of immunologic or inflammatory responses. In the present study, IFN-gamma consistently increased LPS-induced IL-1, but reduced the total amount of IL-1-induced IL-1 from PBMC. This reduction was observed in populations of adherent cells and cells selected with anti-Leu M3 antibody. On a molar basis, IFN-gamma and IFN-alpha 2 were equally effective in reducing IL-1-induced IL-1 synthesis. In PBMC of 24 human subjects, IFN-gamma also reduced PMA-induced IL-1 synthesis (67% decrease, p less than 0.001). The augmentation of LPS-stimulated IL-1 by IFN-gamma was observed only when added at the same time as LPS, but IFN-gamma could be added 6 h after stimulation with IL-1 and still suppress IL-1 production. LPS-induced mRNA for IL 1 beta was modestly enhanced by IFN-gamma whereas mRNA levels for TNF were markedly increased. In contrast, IFN-gamma suppressed mRNA accumulation for IL beta after stimulation with IL-1 alpha by 60 to 95%. The addition of IFN-gamma 30 min before stimulation of PBMC with IL-1 suppressed IL-1 beta mRNA for up to 30 h. The half-life of IL-1 beta mRNA of approximately 2 h was not influenced by IFN gamma. Thus, IFN-gamma reduces IL-1-induced IL-1 synthesis by suppressing IL-1 induced transcription, whereas the same concentrations of IFN-gamma augment LPS induced IL-1 production by increasing transcription. PMID- 2107256 TI - Degradation of IgA proteins by Pseudomonas aeruginosa elastase. AB - Human colostral IgA and myeloma proteins of both IgA1 and IgA2 subclasses were susceptible to cleavage by Pseudomonas aeruginosa elastase. Detailed analysis of the cleavage products of IgA myeloma proteins revealed complete degradation of Fab with no evidence of intact Fab fragments as intermediate cleavage products. In contrast, both IgA1 and IgA2 proteins were resistant to cleavage by alkaline protease from P. aeruginosa. The susceptibility of human IgA proteins to elastase suggests a mechanism by which P. aeruginosa might evade the potentially protective function of IgA by producing this enzyme. PMID- 2107257 TI - Inhibitors of C1q biosynthesis suppress activation of murine macrophages for both antibody-independent and antibody-dependent tumor cytotoxicity. AB - The inhibitors of C1q biosynthesis and secretion, 3,4-dehydro-DL-proline (DHP) and 2,2'-dipyridyl, were previously shown to suppress murine macrophage FcR dependent phagocytosis and cytolysis of IgG-opsonized RBC targets. Inasmuch as non-antibody macrophage activators also bind C1q to initiate C1 activation, we determined the effects of these same inhibitors of C1q biosynthesis on activation of macrophages for antibody-independent, nonspecific tumor cytotoxicity by lipid A and a variety of other non-antibody activators. Preexposure of mouse inflammatory peritoneal macrophages to either DHP (0.5 to 2.5 mM) or 2,2' dipyridyl (0.1 to 0.3 mM) for 24 h produced a dose-related suppression of their response to activation by lipid A to mediate tumor cytotoxicity of L1210 mouse leukemia targets. Inhibition of C1q secretion by DHP-treated macrophages was confirmed both by a complement hemolytic assay and by autoradiographic analysis of [35S]methionine-labeled culture supernatants. DHP-treated macrophages were inhibited in their response to direct activation and triggering of IFN-gamma primed macrophages by lipid A, Poly I:C, and cobra venom factor for tumor cytotoxicity. DHP inhibited macrophage activation for antibody-dependent cellular cytotoxicity of L1210 tumor targets mediated by antitumor target IgG. The addition of exogenous purified C1q (2 micrograms/ml) to macrophages after DHP treatment, reconstituted their response to activation for both antibody independent and antibody-dependent tumor cytotoxicity. Our results indicate that C1q synthesis and secretion by effector macrophages is a prerequisite for the initiation of their activation by both immune complex and by non-antibody agents that also bind C1q. It now appears that macrophage-derived C1q may act as an auxiliary amplification signal for autocrine-like modulation of the initiation of macrophage activation by both the antibody-dependent and independent pathways. PMID- 2107258 TI - Altered signal transduction secondary to surface IgM cross-linking on B-chronic lymphocytic leukemia cells. Differential activation of the phosphatidylinositol specific phospholipase C. AB - To further study the mechanisms by which surface Ig triggering activates the inositol phospholipid signaling pathway, we have used B cells from chronic lymphocytic leukemia patients which, as previously described, display two patterns of response upon sIg cross-linking: in one group this cross-linking induces an inositol phosphate release, an intracellular free Ca2+ concentration elevation and a subsequent cell proliferation; in a second group none of these events occur although there is an increased class II Ag expression following anti mu stimulation as in the first group. We have been able to demonstrate that the phosphatidyl inositol specific phospholipase C (PI-PLC) can be activated in permeabilized B cells from the first group by direct stimulation, with GPT gamma S, of a guanine nucleotide binding (G) protein. In addition, since anti-mu + GTP gamma S stimulate an increased inositol phosphate production in these cells, this suggests that surface Ig cross-linking activates PI-PLC via a G protein. However, in cells from the second group no inositol phosphate is released after GTP gamma S stimulation although PI-PLC can be directly activated by high Ca2+ concentrations. This reflects in these cells, an interruption of the signaling cascade sIg/G protein/PI-PLC at the level of the G protein or at the G protein/PI PLC coupling. In cells from both groups PMA treatment, which is known to alter phosphatidyl inositol metabolism in B cells, completely inhibits PI-PLC activation even by high Ca2+ concentrations. These studies show that the phosphatidyl inositol-dependent signaling cascade after surface Ig triggering can be altered at different levels in B cells. PMID- 2107259 TI - The predominance of CD8+ T cells after infection with measles virus suggests a role for CD8+ class I MHC-restricted cytotoxic T lymphocytes (CTL) in recovery from measles. Clonal analyses of human CD8+ class I MHC-restricted CTL. AB - Stimulation of PBMC, in children recovering from acute measles, with autologous EBV-transformed and measles virus (MV)-infected lymphoblastoid cell lines (B-LCL) expanded primarily MV-specific CD8+ T cells. A large number of CD8+ T cell clones were obtained either by passaging of bulk cultures at limiting dilutions or by direct cloning of PBMC without previous stimulation in bulk culture. The MV specific CD8+ T cell clones responding in a proliferative and a CTL assay were found to be class I MHC restricted. In contrast, CD4+ MV-specific T cell clones, which were generated by the same protocol, recognized MV in association with class II MHC molecules. Analysis of processing requirements for Ag presentation to CD8+ and CD4+ T cell clones, measured by the effect of chloroquine in a proliferative T cell response, revealed that both types of T cells recognized MV Ag processed via the endogenous/cytoplasmic pathway. Thus, these studies indicate that, as in most other viral infections and in contrast to previous suggestions, the class I MHC-restricted CTL response by CD8+ T cells may be an important factor in the control and elimination of MV infection. Therefore, the role proposed for CD4+ class II-restricted T cells in recovery from measles needs to be reevaluated. PMID- 2107260 TI - Flow cytometric measurement of cytoplasmic free calcium in human peripheral blood T lymphocytes with fluo-3, a new fluorescent calcium indicator. AB - Cytoplasmic free calcium [( Ca2+]i) is a key intracellular messenger in many cell types. We have used fluo-3, a recently developed calcium probe, to study [Ca2+]i in resting and stimulated human peripheral blood T lymphocytes. The spectral properties of fluo-3 permit analysis of [Ca2+]i in flow cytometers with a 488 nm argon laser excitation source and fluorescein filter settings. The data obtained with fluo-3 are both qualitatively and quantitatively in good agreement with the data in the literature. After stimulation of T lymphocytes with the mitogens phytohaemagglutinin, concanavalin A and with OKT3, and anti-CD3 monoclonal antibody, a biphasic [Ca2+]i response was observed, with an early EGTA insensitive [Ca2+]i rise, followed by an EGTA-sensitive sustained [Ca2+]i plateau. Non-mitogenic monoclonal antibodies directed against the CD5, CD28 and CD7 T cell surface antigens elicited [Ca2+]i rises only when crosslinked on the cell surface with goat anti-mouse IgG. Conversion of fluorescence data into absolute [Ca2+]i values by means of a non-disruptive calibration procedure, yielded a [Ca2+]i of 107 +/- 18 nM (mean +/- SD, n = 13) in resting T lymphocytes. Time-dependent loss of cellular dye content limits the precision of the calibration procedure in experiments of longer duration. We conclude that fluo-3 promisingly extends the potential application field of flow cytometers with 488 nm argon lasers to [Ca2+]i studies in T lymphocytes. PMID- 2107261 TI - Enzymatic distinction between two subgroups of autosomal recessive lamellar ichthyosis. AB - It has been proposed that the autosomal recessive lamellar ichthyoses may be divided into two subgroups, the erythrodermic (EARLI) and non-erythrodermic (NEARLI) forms. We report measurements of the enzymes beta-glucosidase, a recently described phosholipase, a short-chain carboxylesterase ("butyrase"), and a long-chain carboxylesterase ("palmitase") in aqueous extracts of scales from patients diagnosed according to clinical and micromorphologic criteria, and show that beta-glucosidase and phospholipase tend to be lower in the EARLI group, whereas butyrase is relatively low in the NEARLI group. The internal ratio of either butyrase/glucosidase or butyrase/phospholipase yields a clear separation of the two subgroups, supporting the concept of heterogeneity in this group of diseases. PMID- 2107262 TI - High levels of c-fos proto-oncogene expression in normal human adult skin. AB - The proto-oncogene c-fos is thought to play an important role in the modulation of cell growth and differentiation. In normal tissues that have been studied to date, c-fos expression has been found to be regulated in a tissue-specific manner. Actually, little is known about its expression in normal human adult skin (NHAS). Moreover, the epidermis is a useful tissue to study the role of cellular oncogenes because keratinocytes can be observed simultaneously in their proliferative as well as differentiated state. We studied c-fos expression in NHAS using different molecular approaches which permit us to characterize and localize c-fos products within the epidermis, specifically, at the RNA level by Northern blot and in situ hybridization, and at the protein level by immunofluorescence and Western blotting. Here, we show that both c-fos mRNA and protein are present at high levels in NHAS. These results contrast with the low level of c-fos expression reported for most human adult tissues. Furthermore, c fos expression is visible throughout the epidermal layers indicating that it is not restricted to proliferating basal cells. The epidermis, therefore, represents the first human adult tissue where c-fos is expressed at high levels in vivo and provides an interesting model to further elucidate the role of this proto oncogene in normal and pathologic conditions. PMID- 2107263 TI - Retinoic acid is a potent inhibitor of inducible pigmentation in murine and hamster melanoma cell lines. AB - Melanocyte-stimulating hormone (MSH) induces melanogenesis in Cloudman mouse melanoma cells. The activities of two enzymes in the melanogenesis pathway, tyrosinase and dopachrome conversion factor, are increased as part of the induction process. Trans retinoic acid (RA), at concentrations as low as 0.1 nM, inhibited the induction of tyrosinase, dopachrome conversion factor, and melanogenesis, but had no effect on the basal levels of either enzyme or of cellular melanin content. Half-maximal effects of RA occurred at a concentration of 10 nM; maximal effects were observed at 1 microM. The effects of RA on melanogenesis were independent of its effects on cellular growth since one Cloudman line tested was growth-inhibited by RA and another was growth-stimulated by RA, but the induction of melanogenesis by MSH in both lines was inhibited by RA. Mixing experiments with cell lysates failed to demonstrate the induction of a tyrosinase inhibitor by RA. The effects of RA were not limited to MSH or to Cloudman melanoma cells since RA blocked cholera toxin-inducible melanogenesis in Cloudman cells, as well as the induction of tyrosinase activity by L-tyrosine in Bomirski hamster melanoma cells. The effects of RA were specific to melanogenesis, however, since RA did not interfere with MSH-induced changes in cellular morphology and growth. Thus, RA appears to be a new and potent tool for understanding mechanisms regulating induction of the pigmentary system. PMID- 2107264 TI - Immune activation during measles: interferon-gamma and neopterin in plasma and cerebrospinal fluid in complicated and uncomplicated disease. AB - To study T cell and macrophage activity during measles, levels of interferon gamma (IFN-gamma) and neopterin in plasma and cerebrospinal fluid (CSF) were measured. Plasma levels of IFN-gamma were elevated in measles (1.17 +/- 0.27) compared with healthy adults (0.13 +/- 0.06, P less than .05) and children (0.14 +/- 0.06, P less than .01). Plasma levels of neopterin were elevated in measles (32.5 +/- 2.7) compared with healthy adults (5.3 +/- 2.9, P less than .0001), healthy children (12.1 +/- 4.0, P less than .001), and children with other infectious diseases (20.6 +/- 4.0, P less than .02). IFN-gamma was increased in measles primarily during rash; neopterin remained elevated for several weeks. Levels of neopterin showed a significant positive correlation with plasma levels of soluble interleukin-2 receptor and soluble CD8, two other parameters of T cell activation. Children with measles complicated by pneumonia had higher levels of neopterin in serum than those with uncomplicated disease. Children with measles complicated by autoimmune encephalomyelitis had higher levels of neopterin in CSF than those with noninflammatory neurologic disease but lower than those with central nervous system infections. Thus, IFN-gamma seems to be produced in vivo during acute measles virus infection; deficiency of this lymphokine does not appear to correlate with increased susceptibility to secondary infections. PMID- 2107265 TI - Resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360 degrees C: practical and theoretical implications. AB - Scrapie-infected hamster brains and their extracted amyloid fibrils were subjected to formaldehyde and steam autoclaving, alone or in combination. Treatment with formaldehyde before autoclaving stabilized infectivity, whereas treatment after autoclaving was either inactive or further reduced infectivity. In additional experiments on specimens (not treated with formaldehyde) that were subjected to dry heat, a small amount of infectivity still survived a 1-h exposure to temperatures as high as 360 degrees C. These results are consistent with the operation of a comparatively primitive molecular mechanism for the initiation of scrapie agent replication (perhaps an inorganic crystal nucleation step) and the subsequent participation of an organic macromolecule (scrapie amyloid protein) that is susceptible to intramolecular cross-stabilization by formaldehyde. PMID- 2107266 TI - Distribution and excretion of capsular antigen after immunization with Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine. AB - The occurrence of Haemophilus influenzae type b capsular polysaccharide antigenemia and antigenuria following immunization was studied in 48 healthy 2 month-old infants. Each received a conjugate vaccine consisting of H. influenzae type b capsular polysaccharide covalently linked to Neisseria meningitidis serotype b outer membrane protein at 2 and 4 months of age. Infants were alternated at enrollment for collection of blood and urine after either the first or second dose. Specimens were obtained "early" (2-3 days) after immunization and "late" (7 days) after immunization and assayed for antigen. Antigen was detected in the serum of 3 (6%) of 48 infants, uniformly in the "early" specimen obtained after the first dose of vaccine. Antigenuria occurred in 37 (80%) of 46 infants; for greater than or equal to 7 days in 12 (26%). Antigenuria was frequent after administration of the vaccine but antigenemia was not. These data should be considered in the evaluation of an infant with suspected H. influenzae type b invasive disease. PMID- 2107267 TI - Absence of a binding reactivity of human C-reactive protein for immunoglobulin or immune complexes. AB - Because C-reactive protein (CRP) has been identified as a component of circulating immune complexes from patients with inflammatory diseases, we sought to evaluate a potentially clinically important interaction of this acute-phase protein with immunoglobulin or experimentally-prepared immune complexes in vitro. Highly purified human CRP was incubated with a variety of immunoglobulin substrates, including monomeric immunoglobulin G1 (IgG1), a polyclonal IgG, heat aggregated IgG, and human serum albumin/anti-serum albumin complexes. We were unable to detect a significant binding interaction of radioiodinated CRP with any of these materials, using either polyethylene glycol (PEG) precipitation or sucrose density gradient ultracentrifugation. In contrast, binding of radioiodinated human C1q to both aggregated immunoglobulin and immune complexes was readily detected by these techniques. Incubation of radiolabeled CRP with serum samples from 22 patients with active inflammatory diseases and high levels of circulating immune complexes disclosed no difference in the amount of PEG precipitable CRP when compared with serum samples from healthy individuals. However, a radiolabeled commercial preparation of CRP did result in some PEG precipitable radioactivity after incubation with aggregated IgG. These findings provide no support for a biologically important binding interaction of CRP with immunoglobulin or immune complexes, and they suggest that highly purified preparations of CRP should be used in functional studies of this acute-phase protein. PMID- 2107268 TI - Intracranial tuberculoma. AB - In North America, central nervous system involvement by tuberculosis is uncommon. This patient review describes the clinical and radiological features of this unusual neurologic lesion. Special emphasis is given to the methods of arriving at the correct diagnosis, to the efficacy of combination antituberculous therapy, and to the possibility of paradoxical expansion of these lesions during the course of successful treatment. PMID- 2107269 TI - Effect of nasogastric tubes on eustachian tube function. AB - The Eustachian tube acts as pressure equalizing tube between the nasopharynx and the middle ear. It also functions as a conduit for removal of secretions from the middle ear and mastoid air cell system into the post nasal space. Eustachian tube function may be assessed objectively using tympanometric measurements. (Brooks, 1968, Lutman, 1987). The post-operative use of nasogastric Ryles tubes is associated with reduced peak middle ear pressure (mmH2O) and reduced peak compliance volumes (ml) as assessed by tympanometry. In addition changes in the appearance of the tympanic membrane may occur with the protracted use of Ryles tubes. This phenomenon is a transient one. Nasogastric tube-induced Eustachian tube dysfunction is a previously unreported entity. PMID- 2107270 TI - Free and esterified 13(R,S)-hydroxyoctadecadienoic acids: principal oxygenase products in psoriatic skin scales. AB - Characterization of the chemical form and stereo-specificity of the fatty acid derivatives of arachidonic and linoleic acid in psoriatic epidermis is needed to define the enzymatic origin of these compounds and their possible role in pathogenesis. In an analysis of psoriatic skin scales, both free and esterified 13-hydroxyoctadecadienoic acids were the principal fatty acid derivatives, present in mean concentrations of 115 and 17 ng/mg scales, respectively. The analysis included reversed-phase high performance liquid chromatography of the free acid and of its methyl ester, gas chromatography, gas-liquid chromatography mass spectrometry of the methyl ester derivatives, and chiral separation. The free and esterified 13-hydroxyoctadecadienoic acids isolated from the psoriatic scales contained a mixture of the S/R stereoisomers, averaging 1.9:1 for free 13- hydroxyoctadecadienoic acid. These findings are not compatible with the strict S stereospecificity for oxygen insertion exhibited by mammalian lipoxygenase but rather could point to the action of a cyclooxygenase. The demonstration that a hydroxylated fatty acid derivative is esterified in vivo in psoriatic keratinocytes suggests that the physiology of these cells may be altered early in the process of keratinization. PMID- 2107271 TI - Lipid composition and metabolism in megakaryocytes at different stages of maturation. AB - The lipid composition and metabolism of isolated guinea pig megakaryocyte subgroups at various stages of maturation were investigated. Three groups were studied: 1) 67% of megakaryocytes in Group A were immature; 2) Group B was heterogeneous and contained both immature and mature subgroups of megakaryocytes; 3) 92% of megakaryocytes in Group C were mature. Lipid composition was determined by thin-layer chromatography, lipid-phosphorus, and gas-liquid chromatography. Cholesterol, ceramide, and de novo fatty acid synthesis were evaluated with [14C]acetate. [14C]Glycerol was used to assess de novo phospholipid synthesis. 14C-Labeled fatty acids were used to evaluate fatty acid uptake. The phospholipid and cholesterol content was found to be four times greater in mature megakaryocytes than that in immature megakaryocytes, which paralleled the protein content and volume of mature and immature cells. The cholesterol-phospholipid ratio was similar and there were no differences in the phospholipid species in the three groups. Phospholipid and cholesterol synthesis were established in immature megakaryocytes and persisted at about the same level in mature megakaryocytes. The uptake of arachidonic and palmitic acids also occurred primarily in immature cells, while the de novo synthesis of palmitic acid occurs predominantly in mature megakaryocytes. There was an inverse relationship between the uptake of exogenous palmitic acid and fatty acid synthesis, but the uptake of palmitic acid primarily inhibited fatty acid synthesis in mature megakaryocytes. There were differences in the acylation of phospholipid species with arachidonic acid in megakaryocytes at different stages of maturation since the acylation of phosphatidylcholine occurred primarily in immature megakaryocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107272 TI - Phenotypic characterization of the Ath-1 gene controlling high density lipoprotein levels and susceptibility to atherosclerosis. AB - The Ath-1 gene determines the levels of high density lipoprotein (HDL) lipid in response to a high fat diet challenge as well as susceptibility to diet-induced atherosclerosis in mice (Paigen et al. 1987. Proc. Natl. Acad. Sci. USA. 84: 3763 3767). As yet, the identity of the Ath-1 gene and how it acts to affect HDL levels are completely unknown. In an effort to clarify the nature of the gene, we have examined HDL phenotypes in strains carrying either the susceptible or resistant alleles. When challenged with a high fat diet, the susceptible strain C57BL/6 exhibited a marked decrease in the levels of HDL cholesterol and apolipoprotein A-I (apoA-I), the major protein of HDL, whereas the resistant strains C3H and BALB/c maintained high levels of both. Separation of HDL subfractions by polyacrylamide gradient gel electrophoresis revealed that the decrease was particularly striking among the larger HDL species. The rates of synthesis of apoA-I in liver and intestine were similar in the strains and were unaffected by the high fat diet. Although the rates of synthesis of apoA-II and the levels of apoA-II mRNA were decreased in response to the high fat diet, similar decreases were observed in both the susceptible and resistant strains. We conclude that the Ath-1 gene results in a rapid decrease in both HDL lipid and HDL apolipoprotein levels in the susceptible strain in response to the high fat diet and that this is mediated primarily at the level of HDL catabolism. PMID- 2107273 TI - Inhibitory effect of the uterus on plasma and pituitary FSH in rats. AB - Plasma concentrations of FSH and LH were measured in ovariectomized, ovohysterectomized, hysterectomized and sham-operated adult, non-pregnant rats at 3, 14, 21 and 28 days after operation. From day 21 after the operation onwards, there were higher concentrations of FSH in plasma in ovohysterectomized than in ovariectomized animals. The concentration of LH was not influenced by hysterectomy. The inhibitory response of FSH and LH to a single dose of oestradiol was not altered by any of the operations. By 2 weeks after surgery, pituitary FSH content had increased in ovohysterectomized animals compared with ovariectomized ones, but this difference was eliminated when ovohysterectomized animals were treated with crude uterine extract. Pituitary contents of LH and prolactin were not influenced by hysterectomy or by treatment with uterine extract, thus indicating the specificity of an inhibitory effect of the uterus on FSH levels. Treatment of hysterectomized and intact animals with uterine extract resulted in a reduction in the weight of the ovaries of 23-38% (P less than 0.05), indirectly showing the presence of an FSH-inhibiting substance in the extract. Fractionated uterine extract inhibited FSH synthesis by rat pituitary cells in vitro, but had no effect on LH synthesis. Chromatographic analysis indicated that the FSH-inhibiting substance in the uterus has a molecular weight of 10,000-20,000. PMID- 2107274 TI - Reference ranges of lutropin and follitropin in the luliberin test in prepubertal and pubertal children using a monoclonal immunoradiometric assay. AB - Reference ranges of lutropin and follitropin in the luliberin test (60 micrograms/m2 body surface) were established for the various pubertal stages in a large sample of endocrinologically healthy children using a monoclonal immunoradiometric assay (LH and FSH MAIA Clone, Serono Diagnostika, Freiburg, FRG). Qualitatively, the results for lutropin were similar to those already reported from studies using polyclonal RIA's. Lutropin increased gradually throughout pubertal development. Quantitatively, however, the immunoradiometric assay system yielded considerably lower results than polyclonal RIA's. In contrast, follitropin showed a very good linear regression between monoclonal and polyclonal assays. Therefore the former reference ranges for follitropin are still applicable. PMID- 2107275 TI - Arachidonic acid liberated by diacylglycerol lipase is essential for the release mechanism in chromaffin cells from bovine adrenal medulla. AB - Chromaffin cells from bovine adrenal medulla secrete catecholamines on stimulation with acetylcholine. In addition to the activation of the phosphatidylinositol cycle, arachidonic acid is generated, which was thought to be the result of phospholipase A2 activation. We have demonstrated in isolated plasma membranes of these cells that arachidonic acid is generated by a two-step reaction of diacylglycerol and monoacylglycerol lipase splitting diacylglycerol, which originates from the action of phospholipase C on phosphatidylinositols. No phospholipase A2 activity could be detected in plasma membranes so far. External addition of arachidonic acid increases the release in the absence and in the presence of agonist. Inhibition of the diacylglycerol lipase by RHC 80267 suppresses the catecholamine release, which is restored on addition of arachidonic acid. This effect, however, is reversed by lipoxygenase inhibitors, indicating that it is not arachidonic acid itself, but one of its lipoxygenase products, that is essential for inducing exocytosis. PMID- 2107276 TI - Selective increase in S-100 beta protein by aging in rat cerebral cortex. AB - Changes in the concentrations of nervous tissue-related proteins and their isoproteins, such as S-100 proteins (S-100 alpha and S-100 beta), enolase isozymes (alpha-enolase and gamma-enolase), and GTP-binding proteins (Go alpha, Gi2 alpha, and beta-subunits), were determined in the CNS of male rats of various ages (from 2 to 30 months old) by means of enzyme immunoassay. The weights of brains and the concentrations of soluble proteins in the cerebral cortex, cerebellum, and brainstem were constant during the observation period. The concentration of S-100 beta protein, which is predominantly localized in glial cells, increased gradually in the cerebral cortex with age; levels in the 25 month-old rats increased to approximately 150% of the levels in the young (2 month-old) rats. However, the S-100 beta concentrations in the cerebellum and brainstem were relatively constant, showing similar values in rats 2-30 months old. Levels of other proteins, including both neuronal (gamma-enolase and Go alpha) and glial (alpha-enolase and S-100 alpha) marker proteins, did not change significantly with age in the cerebral cortex, cerebellum, and brainstem. These results suggest that there is a close relation between the age-dependent changes of the CNS function and S-100 beta protein levels in the cerebral cortex. PMID- 2107277 TI - Neuroblastoma differentiation involves the expression of two isoforms of the alpha-subunit of Go. AB - The regulation of GTP-binding proteins (G proteins) was examined during the course of differentiation of neuroblastoma N1E-115 cells. N1E-115 cell membranes possess three Bordetella pertussis toxin (PTX) substrates assigned to alpha subunits (G alpha) of Go (a G protein of unknown function) and "Gi (a G protein inhibitory to adenylate cyclase)-like" proteins and one substrate of Vibrio cholerae toxin corresponding to an alpha-subunit of Gs (a G protein stimulatory to adenylate cyclase). In undifferentiated cells, only one form of Go alpha was found, having a pI of 5.8 Go alpha content increased by approximately twofold from the undifferentiated state to 96 h of cell differentiation. This is mainly due to the appearance of another Go alpha form having a pI of 5.55. Both Go alpha isoforms have similar sizes on sodium dodecyl sulfate-polyacrylamide gels, are recognized by polyclonal antibodies to bovine brain Go alpha, are ADP-ribosylated by PTX, and are covalently myristylated in whole N1E-115 cells. In addition, immunofluorescent staining of N1E-115 cells with Go alpha antibodies revealed that association of Go alpha with the plasma membrane appears to coincide with the expression of the most acidic isoform and morphological cell differentiation. In contrast, the levels of both Gi alpha and Gs alpha did not significantly change, whereas that of the common beta-subunit increased by approximately 30% over the same period. These results demonstrate specific regulation of the expression of Go alpha during neuronal differentiation. PMID- 2107278 TI - Magnetic resonance imaging of the brain and spinal cord in cerebrotendinous xanthomatosis. AB - This reports a 40 year old man with cerebrotendinous xanthomatosis who had bilateral cataracts, enlarged Achilles tendons, progressive dementia, gait disturbance and peripheral neuropathy. Electroencephalography, electromyography, and magnetic resonance imaging (MRI) of the brain and spine were performed. Magnetic resonance imaging revealed cerebral, cerebellar and cervical cord atrophy and white matter involvement in the cerebrum and cerebellum correlating well with the clinical findings. To date there has been one previous report of MRI of the brain in cerebrotendinous xanthomatosis and none of the spinal cord. PMID- 2107279 TI - The modern management of Parkinson's disease. PMID- 2107280 TI - The epidemiology of mass breast cancer screening--a plea for a valid measure of benefit. AB - The present paper analyses the epidemiologic effects of mass breast cancer screening. Mass mammography may possibly achieve a breast cancer mortality reduction in relative risk terms. However, this does not necessarily represent a net benefit. It is argued that the benefits and adverse effects of a screening programme must be measured in terms of absolute risks. According to this measure, the mortality reduction achieved by a mass breast screening programme is only one death per approx. 15,000 women-years. Many thousands of mammograms are needed to prevent one cancer death, and for each woman who can derive a direct benefit in terms of a prevented breast cancer death, hundreds of women have to suffer the anxiety of a positive screening mammography. Moreover, it is possible that adverse effects of breast cancer screening may contribute to mortality from other causes. Even with the assumption that screening can save lives, the net health effect of mass breast cancer screening is questionable and appears to be rather detrimental. It may be an error to recommend mass breast screening. PMID- 2107281 TI - A dissent from Dr Schmidt's appraisal of evidence on breast cancer screening. PMID- 2107282 TI - Labeling of human clots in vitro with an active-site mutant of t-PA. AB - Prompt detection of acute thrombosis and its response to treatment with thrombolytic agents generally require angiography. Scintigraphic approaches with labeled antibodies to or components of the coagulation and fibrinolytic systems have been disappointing because of prolonged circulating half-lives of tracers and relatively slow or limited binding to thrombi. Accordingly, we developed and characterized a thrombolytically inactive, active-site mutant (Ser-478----Thr) of tissue-type plasminogen activator (t-PA) designed to detect thrombi in vivo. Binding of iodine-125-(125I) labeled Ser----Thr t-PA to thrombi in vitro was time and concentration-dependent, and specific judging from inhibition by pre incubation with anti-t-PA IgG. Clearance of 125I-labeled mutant t-PA in rabbits was rapid and biexponential (alpha t1/2 = 1.9 +/- 0.4 min, beta t1/2 = 39.8 +/- 11.2 min). Thus, the amidolytically inactive mutant of t-PA designed binds rapidly and specifically to human thrombi in vitro and is cleared rapidly from the circulation in vivo--properties rendering it attractive as a potentially useful clot imaging agent. PMID- 2107283 TI - Metabolism of indium chelates attached to monoclonal antibody: minimal transchelation of indium from benzyl-EDTA chelate in vivo. AB - The metabolism of radiolabeled antibodies is important for radioimmunoimaging and therapy. The loss of indium-111 (111In) from the chelate can pose problems in imaging and increases the radiation dose to normal tissues. We have evaluated the loss in vivo of 111In from Lym-1-benzyl-EDTA-111In (an antibody conjugated with isothiocyanato-benzyl-EDTA) in normal mice. A monoclonal antibody (CHA 255) that binds to benzyl-EDTA-indium chelates, but not to other forms of indium, was used to measure the percent of 111In remaining in the chelate. Four days after injection, 97.4 +/- 2.2% of the 111In in the liver was still in the benzyl-EDTA chelate, as was 99.4 +/- 0.7% of the 111In in the urine, and 99.1 +/- 0.7% of the 111In in the blood. Studies in vitro indicate that a benzyl-EDTA-111In-antibody chelate conjugate is more stable in human serum than a benzyl-DTPA-111In conjugate, and that both benzyl-chelate conjugates are much more stable than an unsubstituted DTPA conjugate. PMID- 2107284 TI - Effects of feeding rats low protein diets containing casein or soy protein isolate supplemented with methionine or oligo-L-methionine. AB - The effects of supplementing 8% casein or 10% soy protein isolate (SPI) diets with graded levels of oligo-L-methionine (a mixture of hexa- and heptapeptides, OM) or L-methionine (Met) were studied in rats to determine the reason for the difference in nutritional quality between proteins and corresponding amino acid mixtures. As the OM concentration of the casein-based diet was increased from 0.02% to 0.6%, maximum weight gain was attained at 0.2%, and the growth-promoting activity of OM was comparable to Met at all the corresponding levels tested. Liver fat began to accumulate when supplemental Met reached a level of 0.08% of the casein diet, but OM addition did not produce a fatty liver at dietary levels of less than 0.3%. When SPI was used as the dietary protein source, the effect of supplemental OM was significantly less than that of Met. Digestibility of OM (assessed by incremental portal plasma Met concentration) was measured 30 min after feeding the casein or SPI diet supplemented with 3% OM using rats fasted for 24 h. Plasma Met concentration was greatly increased in rats fed the casein plus OM diet compared with that of rats fed the SPI + OM diet. Similarly, the 30 min portal Met concentration significantly increased in response to the casein + OM diet compared with the SPI + OM diet regardless of the prefed proteins (25% casein and 25% SPI for 2 wk).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107285 TI - Complement C3 deposition onto bacteria by neonatal serum is not enhanced after the infusion of intravenous immunoglobulin. AB - To determine the effect of intravenous immunoglobulin (IVIG) on the capacity of serum from septic neonates to deposit complement C3 and IgG onto the bacteria isolated from their blood, 500 mg/kg of IVIG was administered to 18 neonates suspected of being septic. Blood was obtained just before the infusion, and again 15 minutes after its completion. Group B streptococcus type II, group B streptococcus type III, Staphylococcus aureus, and Staphylococcus epidermidis were isolated from the pre-infusion blood of four neonates. Bacteria were incubated with the appropriate serum, washed, and the amount of C3 and IgG subsequently bound to the organisms was quantified by radioimmunobinding assay. Sera from the four septic neonates and sera from four neonates of similar gestational age but whose blood cultures were negative were compared with pooled sera from healthy adults. Before the administration of IVIG, C3 deposition onto the bacteria by sera from five of the seven neonates tested was significantly less than that observed for adult sera. Following the infusion, no increase in C3 deposition was observed for any of the seven sera assayed, and in two cases C3 deposition fell significantly. In contrast, in seven of eight cases, IVIG enhanced the IgG deposition to levels greater than or equal to those observed for adult sera. Therefore, following the infusion of IVIG into neonates with proven or suspected sepsis, the deposition of C3 onto invasive bacteria by their serum was not enhanced even though IgG deposition was increased. PMID- 2107286 TI - Effects of position changes on transcutaneous carbon dioxide tension in neonates with respiratory distress. AB - Routine neonatal care includes frequent position changes. Recent research has concluded that positions other than supine may result in beneficial physiologic responses. Specifically, several studies suggest that neonates may ventilate more effectively in a prone rather than in a supine position. This study tested the hypothesis that transcutaneous carbon dioxide tension (TcPCO2) would be lower in the prone than in the supine position in neonates with respiratory distress. Fourteen ventilated infants were studied. TcPCO2 was measured and recorded in prone, supine, and right-side-lying positions for each subject. There were no statistically significant differences in mean TcPCO2 values between the three positions (F = .45; df 2,39; P = .64). The relationship between TcPCO2 and PaCO2 values was stable (r = .88) during the studies. The results indicate that changing a neonate's position does not significantly alter transcutaneous carbon dioxide tension. PMID- 2107287 TI - Diagnostic test restraint and the specialty consultation. AB - OBJECT: To assess the effect consultants had on the diagnostic process in the management of patients admitted to the medical service of a university hospital. DESIGN: Cohort study utilizing prospective evaluation by residents, retrospective chart review, and direct communication with the patient, a family member, or the patient's physician one year after admission to the hospital. SETTING: The medical inpatient service of an urban university hospital. PATIENTS: The 580 patients admitted to the medical service during one month in 1984 for whom complete data were available. MAIN RESULTS: Sixty-three percent of the patients had consultations. Seventy percent (198/284) of the patients admitted by generalists had consultations, while 57% (170/296) of the patients admitted by subspecialists had consultations. Of the 1,422 major diagnostic tests performed on these patients, 504 (35%) were first recommended by consultants, and the consultants recommended cancellation of only ten major diagnostic tests. Patients who were seen by consultants had a length of stay that was more than double that of patients not seen by consultants. Consultation was associated with prolonged stay when patients were stratified by important clinical variables and remained an important independent factor in a multivariate model. The prolongation of hospitalization was principally due to delays in scheduling and interpreting sophisticated tests recommended by the consultants. When stratified into prognostically similar clinical groupings, there was no significant difference in in-hospital mortality between patients seen and those not seen by a consultant. CONCLUSION: Efforts to foster diagnostic restraint in the management of hospitalized patients should be broadened to include attention to the specialty consultation process. PMID- 2107288 TI - Monoclonal versus polyclonal antibody therapy for prophylaxis against rejection after heart transplantation. AB - Between August 1986 and December 1987, 88 patients received either RATG or OKT3 for immunoprophylaxis before heart transplantation. By the end of the first month after transplantation, 25% of the patients who received RATG had experienced a rejection episode compared with 43% of those receiving OKT3. This difference was persistent as many as 4 months after transplantation. While 50% of the OKT3 patients had a second episode of rejection, only 35% of the RATG patients did so. Randomization of these agents was complicated by severe cardiopulmonary side effects attributed to the first dose of OKT3. Five hours after the first dose of OKT3, a 25% drop in mean arterial pressure, accompanied by significant hypoxia, was seen in a majority of patients. There was no difference in the incidence of infection between the two groups. PMID- 2107289 TI - A prospective assessment of nutritional status and complications in patients with fractures of the hip. AB - A group of 40 consecutive patients with hip fractures were studied and confirmed to have a high incidence of protein-calorie malnutrition. The prospective nutritional assessment performed for this study included: serum albumin, serum transferrin, anthropometric measurements, skin testing for delayed hypersensitivity, total lymphocyte count, and a 24-h urine collection for metabolic and nitrogen balance determinations. At 3 months after their hip fracture, 37.5% returned to their premorbid ambulatory status; 42.5% sustained a decrement in their ambulatory status or independence; 12.5% died; 7.5% were lost to follow-up. Of the nutritional parameters studied, albumin was significantly associated with mortality (p = 0.004). Considering those patients with an albumin less than 3.0, a mortality rate of 70% was observed in follow-up (maximum of 11 months), compared with a mortality rate of 18% in patients with an albumin greater than or equal to 3.0. It is concluded that the serum albumin has value as a nutritional index without specialized nutritional parameters, and that a more aggressive approach to nutritional support is needed for the hypoalbuminemic patient with a hip fracture, particularly for those with a serum albumin below 3.0. PMID- 2107290 TI - Use of Chernoff faces to follow trends in laboratory data. AB - Graphical representation of laboratory data speeds up recognition of abnormalities. The Chernoff face is an excellent tool to represent patient data; the human eye and mind are exquisitely sensitive to subtle changes in facial appearances and expression. One of the best uses of the faces is in illustrating trends in the data, particularly in acutely ill patients where many laboratory studies are performed. The faces are especially useful if comparisons to a former or normal state are made. A very brief examination of adjacent faces suffices to identify changes in laboratory data. PMID- 2107291 TI - Clinical assessment of the Hitachi 736-30 chemistry analyzer. AB - We assessed the Hitachi 736-30 as a possible replacement for the SMAC I and as a laboratory cost-saving measure. For 24 analytes, both intra- and interassay precisions were acceptable; they also had good measuring ranges. Essentially no interference from lipemia was observed, while minimal interference from bilirubin was demonstrated. Hemoglobin interfered in the measurement of 12 of the analytes. Correlation with the SMAC I, Demand, Astra-8, ACA, and Varian Atomic Absorption Spectrophotometer was found to be acceptable, except for chloride which showed poor correlation with SMAC I and Astra-8 (Hitachi = 0.888 [SMAC] + 11.102, r = 0.9652; Hitachi = 0.885 [Astra] + 10.264, r = 0.9136). The Hitachi 736-30 offers reagent and method flexibility, high volume capability, and "walk-away" operation. PMID- 2107292 TI - Hematoporphyrin derivatives: an oligomeric composition study. AB - The oligomeric composition of HpD, Photofrin II and other hematoporphyrin derivatives useful for the diagnosis and therapy of tumors has been studied. Gel chromatographic procedures were used that excluded porphyrin aggregation. Photofrin and hematoporphyrin derivatives were shown to contain different quantities of monomer, dimer and other oligomeric porphyrins. PMID- 2107293 TI - Transmembrane potential measurement with carbocyanine dye diS-C3-(5): fast fluorescence decay studies. AB - The mechanism of carbocyanine dye diS-C3-(5) fluorescence intensity variations with transmembrane potential changes has been studied using time-resolved fluorescence spectroscopy. Clear evidence is given of the transmembrane-potential dependent partition of the dye among various sites with different fluorescence lifetimes. It was found that fluorescence decay profiles reflect the transmembrane potential changes. PMID- 2107294 TI - The mechanism of photohaemolysis by photoproducts of nalidixic acid. PMID- 2107295 TI - Mutagenic and genotoxic properties of singlet oxygen. PMID- 2107296 TI - Identification of hypoxic and oxygenated tumor subpopulations with enzyme and fluorescent probes. PMID- 2107297 TI - Total hemolytic complement (CH50) and its fractions (C3 and C4) in the sera of diabetic patients with periodontitis. AB - The total hemolytic complement activity (CH50) and its fractions C3 and C4 were determined in 50 patients with Type II or non-insulin dependent diabetes mellitus (NIDDM) and 50 nondiabetic patients with periodontitis. The values were compared with those of 50 age and sex matched controls. An elevation of CH50 was observed in both the diabetic and nondiabetic patients, compared to controls. The diabetic patients with periodontitis showed a significantly higher complement activity compared to nondiabetic patients with periodontitis. The C3 and C4 values were significantly elevated in both diabetic and nondiabetic patients when compared with the control group. The elevation being more pronounced in diabetic groups. PMID- 2107298 TI - Lingual fibrosarcoma induced by 7, 12-dimethylbenzanthracene in the rat. AB - A single injection of 5 mg of 7, 12-dimethylbenzanthracene (DMBA) resulted in a high incidence of lingual fibrosarcoma in 67 Wistar rats. No metastases were found. We studied the influence of age and sex on the incidence, latency of tumors, loss of weight and the spontaneous survival of animals. The method described offers an experimental model for the study of cachexia resulting from upper digestive and respiratory tract cancer. PMID- 2107299 TI - Testicular growth, hormone concentrations, seminal characteristics and sexual behaviour in stallions. AB - Puberty was studied using 15 colts of Quarter Horse phenotype. Total scrotal width was measured every 8 weeks from 48 to 96 weeks. Blood samples were taken from 8 colts at 8, 16 and 24 weeks and then every 4 weeks until 100 weeks to measure changes in LH, FSH and testosterone concentrations. Seminal collections were attempted monthly from 48 to 64 weeks and every 2 weeks thereafter until puberty resumed every 3rd day from 96 weeks for 15 ejaculates. For all collections, times to erection, mount and ejaculation and seminal characteristics were recorded. Age at puberty was defined as the first ejaculate containing 50 x 10(6) spermatozoa, with greater than or equal to 10% motile. Colts were castrated at 2 years to enable determination of daily sperm production (DSP), epididymal sperm reserves and normality of spermatogenesis. Total scrotal width increased linearly from 48 to 96 weeks. Age at puberty averaged 83 weeks (56-97 weeks). Changes in serum concentrations of LH and FSH were parallel, rising at 36-40 weeks, declining after 40 weeks and rising again at 68-80 weeks. Testosterone was low until 68 weeks after which concentrations rose slowly to 80 weeks and increased rapidly to a plateau at 92 weeks. Sexual behaviour and seminal characteristics differed (P less than 0.05) between puberty and 2 years, except for time to erection, time to mount, and percentage of motile spermatozoa. DSP at 2 years averaged 1.7 x 10(9) and daily sperm output (DSO) averaged 1.1 x 10(9). The correlation between DSP and DSO was 0.83 (P less than 0.01). There were 9.57 x 10(9) spermatozoa/epididymis of which 67% were in the cauda. PMID- 2107300 TI - Effect of maternal treatment with altrenogest on pituitary response to exogenous GnRH in pubertal stallions. AB - The pituitary response to exogenous GnRH was studied in 8 colts of Quarter Horse phenotype from 32 to 96 weeks of age. Colts were from dams treated daily from Day 20 to 325 of gestation with (1) 2 ml neobee oil per 50 kg body weight (controls); or (2) 2 ml altrenogest per 50 kg body weight. GnRH challenges (5 micrograms/kg body weight) were administered every 8 weeks from 32 to 96 weeks of age to estimate pituitary content of LH. Blood samples were collected every 20 min for 4 h before GnRH and 15, 30, 45, 60, 90, 120, 180, 240 and 360 min after GnRH. Serum concentrations of LH and FSH were determined for the 2 pre-GnRH and all post-GnRH samples. Baseline concentrations (mean of 2 pre-GnRH samples) of LH and FSH were not affected by treatment (P greater than 0.05). Serum concentrations of LH declined from 40 to 56 weeks and rose again between 72 and 80 weeks. Basal concentrations of FSH declined from 32 to 56 weeks, and varied widely after 56 weeks. The maximum LH response to GnRH (highest concentration after GnRH minus baseline) declined steadily in both groups for 48 to 64 weeks but remained relatively constant in both groups after 64 weeks. The maximum FSH response to GnRH declined from 32 to 64 weeks then remained relatively constant in both groups. The GnRH-induced gonadotrophin release remained low with a transient increase at 72 weeks for both hormones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107302 TI - Luteal-phase defect induced by deprivation of FSH at a specific period of the follicular phase prevents pregnancy in the bonnet monkey (Macaca radiata). AB - Female bonnet monkeys were injected i.v. with 25 microliters antiserum to FSH on Days 5, 6 or 7 of the cycle: the length of the luteal phase was shortened but there was no alteration in cycle length. Proven fertile females (N = 6) were caged throughout the period of the experiment (6 cycles) with proven fertile males and treated with 25 microliters FSH antiserum on Day 7 of each of 3 successive cycles. Out of 18 cycle exposures during the treatment phase, 17 were ovulatory, but no pregnancies occurred. In the post-treatment phase, 5 monkeys became pregnant within 3 cycle exposures. These results show that it is possible to render female monkeys infertile by creating luteal insufficiency and this can be achieved repeatedly in a reproducible manner by depriving the cyclic females of FSH support on Day 7 of consecutive cycles. PMID- 2107301 TI - Effect of maternal treatment with altrenogest on age at puberty, hormone concentrations, pituitary response to exogenous GnRH, oestrous cycle characteristics and fertility of fillies. AB - Puberty was studied using 15 fillies of Quarter Horse phenotype. Fillies were from dams treated daily from Days 20 to 325 of gestation with: (1) 2 ml neobee oil per 50 kg body weight (controls); or (2) 2 ml altrenogest (2.2 mg/ml) per 50 kg body weight. The clitoris was measured at birth and approximately every 12 weeks until 84 weeks of age. Blood samples were collected from 9 fillies (5 treated, 4 controls) every 4 days over a 28-day period at 8-week intervals from 4 to 68 weeks of age; sampling continued every 4 days after 72 weeks of age until first oestrus. Blood samples were collected daily during oestrus (greater than or equal to 35 mm follicle) and on Days 4, 6, 10, and 14 after ovulation for the first 2 oestrous cycles. GnRH challenges (5 micrograms/kg) were administered every 8 weeks from 32 to 96 weeks of age. Puberty was defined as the first oestrus with ovulation. Beginning 1 February 1987, fillies were teased daily and their ovaries were examined by ultrasonography every 3 days (daily during oestrus). Fillies were inseminated with 500 x 10(6) motile spermatozoa from one stallion. Pregnancy was diagnosed by ultrasonography on Days 11, 12, 15 and every 5 days until Day 50 after ovulation. Prenatal altrenogest treatment caused clitoral enlargement (P less than 0.05) and increased serum concentrations of LH from 1 to 7 months of age. The amount of LH released in response to exogenous GnRH was greater (P less than 0.05) in treated fillies at 32, 64, and 72 weeks of age. Treated fillies had higher serum concentrations of FSH from 1 to 4 months (P less than 0.05), but FSH was lower (P less than 0.05) in treated fillies before and during first oestrus. Serum concentrations of LH and FSH peaked transiently at 10 months and LH was depressed from 64 to 88 weeks and began to rise 14 days before first oestrus. Concentrations of FSH began to decline 14 days before first oestrus. The median age at puberty was 90 weeks. Durations of oestrus, dioestrus, and the oestrous cycle were not different between groups and were similar to those for adult mares. First cycle pregnancy rates and overall rates were 100 and 82% and 100 and 91.7% for control and treated fillies, respectively (P greater than 0.05). Maternal treatment with altrenogest did alter gonadotrophin secretion before puberty, but had no effect on functional reproductive performance in fillies. PMID- 2107303 TI - Concentrations of follicle regulatory protein, steroids and gonadotrophins in antral fluids from women stimulated with metrodin and hCG. AB - Concentrations of immunoreactive follicle regulatory protein (FRP) were determined in 184 follicular fluid samples recovered from 30 patients in whom ovarian stimulation before oocyte recovery and in-vitro fertilization was induced with FSH (150 i.u./day). Ovum recovery was scheduled when the diameters of greater than or equal to 2 follicles reached 15-17 mm and serum oestradiol values were 740 pM/follicle. The mean level of FRP in fluid from follicles yielding oocytes which fertilized and cleaved within 48 h of recovery (24.4 +/- 3.08 immunoreactive units [IRU]/ml; 1 IRU = approximately 1 ng pig FRP) was higher than that in fluid from follicles yielding oocytes which did not fertilize (10.5 +/- 1.67 IRU/ml, P less than 0.05). FRP in fluid from follicles yielding oocytes which fertilized but did not cleave within 48 h of recovery was 17.2 +/- 2.89 IRU/ml. Overall, concentrations of FRP did not correlate with follicular fluid volume or with FSH or LH concentrations, but were positively related to prolactin, oestradiol and total protein levels (P less than 0.04). The results indicate that the FRP content of follicular fluid may be predictive of follicle/oocyte maturity. A dose-dependent increase in release of FRP by pig granulosa cells cultured in medium supplemented with 10-100 ng prolactin/ml was demonstrated. Prolactin may, therefore, be an important determinant of FRP production by granulosa cells. PMID- 2107304 TI - Conversion of pregnenolone to progesterone by mouse morulae and blastocysts. AB - When mouse morulae, early blastocysts and implanting blastocysts were cultured with tritiated pregnenolone, tritiated progesterone and its metabolites, 5 alpha pregnan-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one, were isolated from the medium. It appears that mouse embryos can make progesterone from pregnenolone and the progesterone is quickly metabolized into various metabolites. These abilities increase with development. It is suggested that the mouse embryo can make progesterone and may regulate its own progesterone level for optimal development. PMID- 2107305 TI - Gold induced marrow suppression: a review of 10 cases. AB - We have reviewed 10 cases of gold sodium aurothiomalate (GSTM) induced marrow suppression. All had biopsy proven marrow hypoplasia/aplasia. Anemia, neutropenia and thrombocytopenia were observed in 7 of the 10 patients. In 2 patients, hypoplastic marrow was associated with suppression of 2 of the formed elements of the blood, while in one patient, there was isolated neutropenia. Nine of the 10 patients survived. Bone marrow recovery occurred within an average of 5.4 months. A response was seen in 3 with antithymocyte globulin. One patient required an allogeneic bone marrow transplant. A combination of corticosteroids and androgens was associated with recovery in 5. Blood and platelet transfusions and antibiotics were instituted only when clinically indicated. We conclude that the prognosis of GSTM induced marrow suppression is better than previously reported. PMID- 2107306 TI - The Asian Mother and Baby Campaign (the Leicestershire experience). AB - Leicestershire was one of the 10 districts selected for inclusion in the Asian Mother and Baby Campaign, a campaign undertaken to help overcome the problems experienced by Asian women during pregnancy. To achieve this aim eight linkworkers were allocated to this district for a two year period. A local evaluation was undertaken using general practices with evidence of a higher than average perinatal risk. Linkworkers were distributed equally between the hospital and community setting. Women from the selected practices were interviewed at three points; booking for ante-natal care, following delivery and at the post natal visit. It was found that the linkworkers provided a much needed interpreter service but were less successful in imparting health education knowledge to Asian women. In fact improvement in health education knowledge only occurred in women with a good understanding of English. A surprising finding was that there is still a very large proportion (approximately 50%) of Asian women in Leicestershire who are unable to communicate in English and are not therefore able to make full use of the available services. PMID- 2107307 TI - Information needs of patients and visitors in a district general hospital. AB - A survey of the information needs of patients and visitors to a large District General Hospital was conducted during a one-month period in 1988 to identify sources of information used by patients and their visitors, whether these sources were perceived as adequate and what improvements were suggested. The findings indicate that of 406 respondents, 37% had wanted to know more about a particular condition within the preceding 12 months. The most frequently used sources of information were general practitioners, hospital doctors and nurses, and written material. The most frequent inquires were about disease aetiology and prevention, and the treatment and prognosis of a wide range of medical conditions. Thirty-six per cent of the inquirers had received little or none of the information that they sought. Visitors were more likely than patients to be dissatisfied with presently available sources of information, and patients over 60 years old were more likely to be satisfied than younger groups. Dissatisified persons were most often seeking improved access to doctors and nurses, more explanations from these staff, and more readily available booklets and leaflets. The results are discussed in relation to previous findings with hospital in-patients. They support a stated need in the recent Government White Paper, Working For Patients, for patient information leaflets and for clear and sensitive explanations about what is happening to them in hospital. PMID- 2107308 TI - Retirement--a health crisis. PMID- 2107309 TI - Rheumatic heart disease in schoolchildren in western district, Saudi Arabia. AB - The prevalence of rheumatic heart disease was assessed among schoolchildren aged between 6-15 years in the Western District. A sample size of 9,418 (10% of the target population) underwent cardiac evaluation. The prevalence of rheumatic heart disease was 24 per 10,000 schoolchildren (6-15 years). The prevalence was higher in rural areas and in females. This survey revealed that the carrier rate of beta-hemolytic streptococci was 34%. PMID- 2107310 TI - Trends in the organization of cervical cancer screening. AB - Cervical cytological screening has been available in the UK for several decades, but has not achieved a significant reduction in the incidence of and mortality from cervical cancer. In this paper we describe past problems of cervical screening, discuss the impact of recent innovations to computerize call and recall, and suggest further improvements for the future. PMID- 2107311 TI - Retirement courses: should they include nutrition? PMID- 2107312 TI - Road safety management in developing countries. PMID- 2107313 TI - Functional health development model: a tool for planning. AB - This paper describes a functional model (gross style) taking available information about the health sector e.g. indicators of health status, types of service utilization, source allocations and placing these quantities into a systematic framework as a tool for planning for health services in a developing area. The major advantages of functional models over trial-and-error for planning have been presented. The functional model described could contribute to the sorting out of desirable from less desirable policy alternatives for a specific population. The output from the model is useful for matching resources to program development, taking into consideration costs and effectiveness. PMID- 2107314 TI - Training for environmental protection. PMID- 2107315 TI - Control of food poisoning. PMID- 2107316 TI - Rodent control in London's sewers. PMID- 2107317 TI - Serotyping and subtyping of Neisseria meningitidis isolates by co-agglutination, dot-blotting and ELISA. AB - Typing of meningococci with a panel of serotype and subtype specific monoclonal antibodies (MAbs) was compared in co-agglutination, dot-blotting and ELISA tests. Twenty reference strains, 50 case isolates and 133 throat isolates from healthy carriers were studied. The typing results with dot-blotting and ELISA were identical, whereas co-agglutination gave different results for three case and 24 carrier strains. The distribution of serotypes and subtypes among the strains is reported. The combination of the subtypes P1.1 and P1.15 in a serotype 15 patient strain was observed. With one case strain and 15 carrier strains, neither serotype nor subtype could be determined. Non-typable and non-subtypable isolates were further characterised by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Co-agglutination is useful for typing small numbers of strains with a few MAbs, but less suitable for large-scale typing than the other two methods. Dot-blotting needs less expensive equipment, smaller volumes of antibodies and fewer manipulations than ELISA. PMID- 2107318 TI - Bend induced by the phage phi 29 transcriptional activator in the viral late promoter is required for activation. AB - Transcription initiation from the Bacillus subtilis phage phi 29 late A3 promoter requires the viral protein p4, a transcriptional activator. Protein p4 binds to a region of the A3 promoter, located between nucleotides -50 and -100 relative to the transcription start site, that presents a sequence-directed curvature. This curvature is enhanced when protein p4 binds to the promoter. A number of deletion mutants at the carboxyl end of protein p4 have been constructed and their behavior as transcriptional activators of the late A3 promoter has been investigated. The binding of these deletion mutants to the late A3 promoter has been analyzed by gel retardation, DNase I footprinting, methylation interference and circular permutation assays. The results suggest that the last 12 amino acid residues of protein p4, six of which are positively charged, although not involved in the specific recognition of the promoter are responsible for part of the bend induced by protein p4 in its binding site. Evidence is presented which suggests that full induction of this curvature is needed for the transcription activation process. A model is proposed for protein p4 interaction with the A3 promoter, in which the bend is induced in two steps: first, two monomers of protein p4 bind to the inverted recognition sequences, subsequent interaction between them generating a bend between these sequences; second, the highly basic carboxyl terminus of protein p4 establishes non-specific electrostatic interactions with the DNA backbone inducing a bend at both ends of the protein p4 binding region. PMID- 2107319 TI - Crystallographic refinement and structure of ribulose-1,5-bisphosphate carboxylase from Rhodospirillum rubrum at 1.7 A resolution. AB - The amino acid sequence of ribulose-1,5-bisphosphate carboxylase/oxygenase from Rhodospirillum rubrum has been fitted to the electron density maps. The resulting protein model has been refined to a nominal resolution of 1.7 A using the constrained-restrained least-squares refinement program of Sussman and the restrained least-squares refinement program of Hendrickson & Konnert. The crystallographic refinement, based on 76,452 reflections with F greater than sigma (F) in the resolution range 5.5 to 1.7 A resulted in a crystallographic R factor of 18.0%. The asymmetric unit contains one dimeric ribulose-1,5 biphosphate carboxylase molecule, consisting of 869 amino acid residues and 736 water molecules. The geometry of the refined model is close to ideal, with root mean-square deviations of 0.018 A in bond lengths and 2.7 degrees in bond angles. Two loop regions, comprising residues 54 to 63 and 324 to 335, and the last ten amino acid residues at the C terminus are disordered in our crystals. The expected trimodal distribution is obtained for the side-chain chi 1-angles with a marked preference for staggered conformation. The hydrogen-bonding pattern in the N-terminal beta-sheet and the parallel sheet in the beta/alpha-barrel is described. A number of hydrogen bonds and salt bridges are involved in domain domain and subunit-subunit interactions. The subunit-subunit interface in the dimer covers an area of 2800 A2. Considerable deviations from the local 2-fold symmetry are found at both the N terminus (residues 2 to 5) and the C terminus (residues 422 to 457). Furthermore, loop 8 in the beta/alpha-barrel domain has a different conformation in the two subunits. A number of amino acid side-chains have different conformations in the two subunits. Most of these residues are located at the surface of the protein. An analysis of the individual temperature factors indicates a high mobility of the C-terminal region and for some of the loops at the active site. The positions and B-factors for 736 solvent sites have been refined (average B: 45.9 A2). Most of the solvent molecules are bound as clusters to the protein. The active site of the enzyme, especially the environment of the activator Lys191 in the non-activated enzyme is described. Crystallographic refinement at 1.7 A resolution clearly revealed the presence of a cis-proline at the active site. This residue is part of the highly conserved region Lys166-Pro167-Lys168. PMID- 2107320 TI - Quakes hit California and, perhaps, the central dogma. PMID- 2107321 TI - The nucleotide sequence of five ribosomal protein genes from the cyanelles of Cyanophora paradoxa: implications concerning the phylogenetic relationship between cyanelles and chloroplasts. AB - The nucleotide sequences of the ribosomal protein genes rps18, rps19, rpl2, rpl33, and partial sequence of rpl22 from cyanelles, the photosynthetic organelles of the protist Cyanophora paradoxa, have been determined. These genes form two clusters oriented in opposite and divergent directions. One cluster contains the rpl33 and rps18 genes; the other contains the rpl2, rps19, and rpl22 genes, in that order. Phylogenetic trees were constructed from both the DNA sequences and the deduced protein sequences of cyanelles, Euglena gracilis and land plant chloroplasts, and Escherichia coli, using parsimony or maximum likelihood methods. In addition, a phylogenetic tree was built from a distance matrix comparing the number of nucleotide substitutions per site. The phylogeny inferred from all these methods suggests that cyanelles fall within the chloroplast line of evolution and that the evolutionary distances between cyanelles and land plant chloroplasts are shorter than between E. gracilis chloroplasts and land plant chloroplasts. PMID- 2107322 TI - Oligomerization of cytosine-containing nucleotide analogs in aqueous solution. AB - Bisphosphoimidazolides of 2'-deoxycytidine and of its acyclic analog C can be oligomerized in aqueous solution in the presence of Mn(II). Under certain conditions, a range of products extending to at least the 20mer can be obtained. These products are of interest as possible templates for oligomerization of the complementary monomers. PMID- 2107323 TI - Molecular anatomy: phyletic relationships derived from three-dimensional structures of proteins. AB - A distance measure that reflects the dissimilarity among structures has been developed on the basis of the three-dimensional structures of similar proteins, this being totally independent of sequence in the sense that only the relative spatial positions of mainchain alpha-carbon atoms need be known. This procedure leads to phyletic relationships that are in general correlated with the sequence phylogenies based on residue type. Such relationships among known protein three dimensional structures are also a useful aid to their classification and selection in knowledge-based modeling using homologous structures. We have applied this approach to six homologous sets of proteins: immunoglobulin fragments, globins, cytochromes c, serine proteinases, eye-lens gamma crystallins, and dinucleotide-binding domains. PMID- 2107324 TI - Evolution of proteins of the cystatin superfamily. AB - We have examined the amino acid sequences of a number of proteins that have been suggested to be related to chicken cystatin, a protein from chicken egg white that inhibits cysteine proteinases. On the basis of statistical analysis, the following proteins were found to be members of the cystatin superfamily: human cystatin A, rat cystatin A(alpha), human cystatin B, rat cystatin B(beta), rice cystatin, human cystatin C, ox colostrum cystatin, human cystatin S, human cystatin SA, human cystatin SN, chicken cystatin, puff adder cystatin, human kininogen, ox kininogen, rat kininogen, rat T-kininogens 1 and 2, human alpha 2HS glycoprotein, and human histidine-rich glycoprotein. Fibronectin is shown not to be a member of this superfamily, and the c-Ha-ras oncogene protein p21 (Val-12) probably is not a member also. It was convenient to divide members of the superfamily into four types on the basis of the presence of one, two, or three copies of cystatin-like segments and the presence or absence of disulfide bonds. Evolutionary dendrograms were calculated by three methods, and from these we have constructed a scheme depicting the sequence of events in the evolution of these proteins. We suggest that about 1000 million years ago a precursor containing disulfide loops appeared, and that all disulfide-containing cystatins are derived from this. We follow the evolution of the proteins of the superfamily along four main lineages, with special attention to the part that duplication of segments has played in the development of the more complex molecules. PMID- 2107325 TI - Phyletic aspects of the distribution of 3-hydroxyretinal in the class Insecta. AB - The distribution of 3-hydroxyretinal (R3), a recently discovered retinoid used as the visual pigment chromophore in some insects, was investigated in the class Insecta using HPLC technology. We studied 138 species in 24 orders, sampling from a wide range of taxonomic groups as well as varied habitats. In addition to groups already known to have R3, we find this retinoid in Hemiptera (suborder Heteroptera), Plecoptera, Megaloptera, and Hymenoptera. We also find retinal (R1) in Hemiptera (suborder Homoptera), Mecoptera, and Trichoptera, groups previously thought to have only R3. The pattern of R3 occurrence indicates that this retinoid cannot be considered a phylogenetic marker, having a scattered distribution in the class Insecta as well as within some orders of insects. Several environmental factors that might influence the selection of chromophore have been considered, but none correlates with its distribution. The evolutionary reasons for the pattern of occurrence of R3 therefore remain unknown. PMID- 2107326 TI - A method for molecular phylogeny construction by direct use of nucleotide sequence data. AB - A method for molecular phylogeny construction is newly developed. The method, called the stepwise ancestral sequence method, estimates molecular phylogenetic trees and ancestral sequences simultaneously on the basis of parsimony and sequence homology. For simplicity the emphasis is placed more on parsimony than on sequence homology in the present study, though both are certainly important. Because parsimony alone will sometimes generate plural candidate trees, the method retains not one but five candidates from which one can then single out the final tree taking other criteria into account. The properties and performance of the method are then examined by simulating an evolving gene along a model phylogenetic tree. The estimated trees are found to lie in a narrow range of the parsimony criteria used in the present study. Thus, other criteria such as biological evidence and likelihood are necessary to single out the correct tree among them, with biological evidence taking precedence over any other criterion. The computer simulation also reveals that the method satisfactorily estimates both tree topology and ancestral sequences, at least for the evolutionary model used in the present study. PMID- 2107327 TI - Doublet preference and gene evolution. AB - Doublet preference analysis was carried out on coding and noncoding regions of Escherichia coli, Saccharomyces cerevisiae, and human mitochondrial and nuclear DNA. The preference pattern in 1-2 and 2-3 doublets in E. coli and S. cerevisiae correlated with that in noncoding regions. The 3-1 doublet preference in E. coli genes with low optimal codon frequency and in S. cerevisiae genes also showed a correlation with each of their noncoding doublet preference. A mechanism to explain these double preference correlations in doublet preference is presented: mutational biases, the origin of the noncoding region doublet preference, evolved so as to maintain the 1-2 and 2-3 doublet preference, which is determined by codon usage. These biases then acted on the 3-1 doublet, which was almost free of coding constraints, resulting in a similar preference in this doublet. PMID- 2107328 TI - The biological equilibrium of base pairs. AB - An inherent feature of double-stranded DNA is the possible replacement of any base pair by another one upon replication. A replication-dependent substitution mutation of a matched base pair requires the temporary formation of a mismatched base pair (mispair). A functionally complementary pair of mispairs is ascribed to each of the four types of substitution mutations. Provided that all types of mispairs can be formed, a dynamic biological equilibrium between the four matched base pairs must exist in all DNA, which is directly related to the formation and stability of the corresponding eight mispairs in vivo. Each nucleotide position in a genome can therefore be described as a system of six dynamic equilibria between the four matched base pairs. After a sufficient number of replications, these equilibrium states will express an overall mutation-selection balance for each individual base pair. In a thermodynamic context, the mispairs represent intermediate states on the transformation pathways between the matched base pairs. Catalysts change the stability and probability of formation of intermediate states. Mutagenic proteins are proposed as hypothetical substitution mutation catalysts in vivo. Functionally, they would be capable of recognizing a particular DNA sequence, tautomerizing a nucleotide base thereof, and hence efficiently inducing a specific misincorporation. Phenomenologically such catalysts would accelerate the rates of substitution mutations and provide pathways for directional mutation pressure. PMID- 2107329 TI - Evolution of a protein superfamily: relationships between vertebrate lens crystallins and microorganism dormancy proteins. AB - A search of sequence databases shows that spherulin 3a, an encystment-specific protein of Physarum polycephalum, is probably structurally related to the beta- and gamma-crystallins, vertebrate ocular lens proteins, and to Protein S, a sporulation-specific protein of Myxococcus xanthus. The beta- and gamma crystallins have two similar domains thought to have arisen by two successive gene duplication and fusion events. Molecular modeling confirms that spherulin 3a has all the characteristics required to adopt the tertiary structure of a single gamma-crystallin domain. The structure of spherulin 3a thus illustrates an earlier stage in the evolution of this protein superfamily. The relationship of beta- and gamma-crystallins to spherulin 3a and Protein S suggests that the lens proteins were derived from an ancestor with a role in stress-response, perhaps a response to osmotic stress. PMID- 2107330 TI - The rat P450 IID subfamily: complete sequences of four closely linked genes and evidence that gene conversions maintained sequence homogeneity at the heme binding region of the cytochrome P450 active site. AB - Four genes in the P450 IID gene subfamily were isolated from Sprague-Dawley rat lambda EMBL 3 and Charon 4A genomic libraries and completely sequenced. Their transcription start sites were determined by primer extension analysis. The four genes designated IID2, IID3, IID4, and IID5 span 4036, 4371, 4678, and 4567 bp, respectively, and are closely linked head to tail on a 60-kb segment of DNA. All IID genes contained nine exons, and interestingly, the IID2, IID3, and IID4 genes possessed an atypical GC5' splice junction in intron 2. All four genes are transcribed, however, IID4 mRNA is produced at a level of less than one-tenth of those of IID2, IID3, and IID5. The exonic regions of these genes displayed from 79 to 84% sequence similarties. Several regions of extremely high nucleotide similarity were found within the introns, exons, and in the flanking regions of the four genes. These localized areas of high nucleotide similarities are the result of former gene conversion events. Of interest was the finding that the most highly similar region of all IID genes that was maintained by gene conversion covers portions of the eighth and ninth exons and the eighth intron. The ninth exon codes for a region of the P450 protein that is well conserved among all P450 gene families and in all species and that is associated with the noncovalently bound heme iron at the enzyme's active site. These data indicate that gene conversions have maintained sequence homogeneity within a critical region of the four P450 IID proteins. PMID- 2107332 TI - Conservatism of sites of tRNA loci among the linkage groups of several Drosophila species. AB - The sites of seven tRNA genes (Arg-2, Lys-2, Ser-2b, Ser-7, Thr-3, Thr-4, Val-3b) were studied by in situ hybridization. 125I-labeled tRNA probes from Drosophila melanogaster were hybridized to spreads of polytene chromosomes prepared from four Drosophila species representing different evolutionary lineages (D. melanogaster, Drosophila hydei, Drosophila pseudoobscura, and Drosophila virilis). Most tRNA loci occurred on homologous chromosomal elements of all four species. In some cases the number of hybridization sites within an element varied and sites on nonhomologous elements were found. It was observed that both tRNA(2Arg) and tRNA(2Lys) hybridized to the same site on homologous elements in several species. These data suggest a limited amount of exchange among different linkage groups during the evolution of Drosophila species. PMID- 2107331 TI - GC balance in the internal transcribed spacers ITS 1 and ITS 2 of nuclear ribosomal RNA genes. AB - The internal transcribed spacer (ITS) 1 and 2, the 5.8S rRNA gene, and adjacent 18S rRNA and 25S rRNA coding regions of two Cucurbitaceae (Cucurbita pepo, zucchini, ITS 1: 187 bp, and ITS 2: 252 bp in length, and Cucumis sativus, cucumber, ITS 1: 229 bp, and ITS 2: 245 bp in length) have been sequenced. The evolutionary pattern shown by the ITSs of these plants is different from that found in vertebrates. Deletions, insertions, and base substitutions have occurred in both spacers; however, it is obvious that some selection pressure is responsible for the preservation of stem-loop structures. The dissimilarity of the 5' region of ITS 2 found in higher plants has consequences for proposed models on U3 snRNA-ITS 2 interaction in higher eukaryotes. The two investigated Cucurbitaceae species show a G + C content of ITS 1 that nearly equals that of ITS 2. An analysis of the ITS sequences reveals that in 19 out of 20 organisms published, the G + C content of ITS 1 nearly equals that of ITS 2, although it ranges from 20% to 90% in different organisms (GC balance). Moreover, the balanced G + C content of the ITSs in a given species seems to be similar to that of so-called expansion segments (ESs) in the 25/28S rRNA coding region. Thus, ITSs show a phenomenon called molecular coevolution with respect to each other and to the ESs. In the ITSs of Cucurbitaceae the balanced G + C composition is at least partly achieved by C to T transitions, via deamination of 5-methylcytosine. Other mutational events must be taken into account. The appearance of this phenomenon is discussed in terms of functional constraints linked to the structures of these spacers. PMID- 2107333 TI - Malnutrition among children of adolescent mothers in a squatter community of Recife, Brazil. AB - In a study of 357 first time mothers in a squatter community of Recife it was found that 1 in 10 were less than 15 years old and 60 per cent less than 20 at the time of their first delivery. Two groups of mothers were distinguished, viz. adolescent mothers with a mean (SD) age at first delivery of 16.7 (0.78) years and older mothers with a mean (SD) age at first delivery of 25 (0.79). More than a third were living in common-law union. Of the adolescent mothers only 58 per cent were living with the child's father. A further 23 per cent had received financial support from their own parents during the pregnancy. The rest were expelled from home. The adolescent mothers were generally worse off with a per capita income generally half of that of older mothers. About a quarter of all children studied were below the 10th centile of NCHS standards (23 per cent by weight/age; 28 per cent by height/age). The undernourished first born was 2.5 times more likely to have an adolescent mother, four times more likely to be in a household with low income, and two times more likely to have an illiterate mother as compared to the first borns who remain well nourished. The implications of these findings for urban primary health care programmes are further discussed. PMID- 2107334 TI - Recurrent generalized seizures of long duration. PMID- 2107335 TI - Combined cystourethropexy for the treatment of type 3 and complicated female urinary incontinence. AB - We treated 37 women with type 3 stress urinary incontinence or with an associated complicating factor, such as morbid obesity, a large or proximal diverticulum or a urethrovaginal fistula, via combined transvaginal cystourethropexy. All women with type 3 stress incontinence had failed a previous anti-incontinence operation. Patients in both groups underwent suprapubic needle suspension and an additional bladder neck support procedure. Among 33 patients who underwent preoperative urodynamic studies 30 had stable bladders (90%), while 3 had low pressure detrusor instability (10%). The success rate in achieving continence, including cured and improved patients, was 94.6% with a followup of 3 to 72 months. Four patients (10%) required temporary intermittent catheterization for 3 to 4 weeks but none presented with long-term voiding dysfunction. The added bladder neck support improved our results in these complicated female incontinence cases compared to the standard suprapubic needle suspension procedures alone. The combined procedure currently is our method of choice for treatment of type 3 and other complicated cases of female urinary incontinence. PMID- 2107336 TI - Topical glyceryltrinitrate causes measurable penile arterial dilation in impotent men. AB - The current understanding of the intracavernous changes that cause or accompany penile erections has encouraged the use of vasodilators as therapy for erectile dysfunction. An established vasodilator, glyceryltrinitrate, was selected for in vivo study because of its rapid transdermal absorption. Color coded duplex ultrasound was used to assess penile vascular response. In a large group of men with erectile dysfunction significant dilation was noted in response to a small amount of nitroglycerine paste applied to the penis. There is a measurable vasodilatory response that can be induced by synthetic nitrates in penile tissue in impotent men. PMID- 2107337 TI - Mediation of micturition reflex by central norepinephrine from the locus coeruleus in the cat. AB - We examined whether norepinephrine originating in the locus coeruleus mediates the micturition reflex in anesthetized cats. 6-Hydroxydopamine, a catecholamine neurotoxin, injected bilaterally into the locus coeruleus markedly decreased catecholamine fluorescence in the lesioned area and induced urinary retention after 72 to 84 hr. At this time, there was no or only slight contraction of the urinary bladder induced by its distension, while the contraction was noted before the treatment. However, phenylephrine, an alpha 1-receptor agonist, applied intrathecally in 6-hydroxydopamine-treated animals induced moderate bladder contraction. In sham-operated animals, the bladder contraction on its distension was inhibited by intrathecally applied prazosin, an alpha 1-receptor antagonist. Thus, in the micturition reflex, norepinephrine derived from the locus coeruleus acts on the alpha 1-adrenergic receptors in the sacral cord, and induces urinary bladder contraction via activation of the sacral parasympathetic preganglionic neurons. PMID- 2107338 TI - Effects of outlet obstruction on glucose metabolism of the rabbit urinary bladder. AB - Bladder outlet obstruction has been shown to cause detrusor contractile dysfunction. To determine if alterations in bladder metabolism may in part underlie these functional defects, we investigated the effects of mild outlet obstruction on the glucose metabolism of the rabbit urinary bladder. Mild outlet obstruction was created in mature male rabbits by the surgical placement of a silicon sleeve around the bladder neck. Two weeks after surgery, the in vitro ability of the obstructed bladder tissues to metabolize glucose was compared to that of the controls. The results can be summarized as follows: 1) The bladder wet weight increased 2.3-fold following two weeks of obstruction. 2) Obstructed bladder tissues had a reduced glucose consumption as compared to the controls. 3) CO2 generation was significantly reduced by 31% in obstructed bladder tissues whereas lactate formation increased significantly by 22%. 4) Tissue concentrations of ATP, creatine phosphate, and glycogen before incubation showed no significant differences between control and obstructed bladder tissues. In summary, bladder tissues following two weeks obstruction showed a decrease in aerobic metabolism and an increase in anaerobic metabolism. Previous studies have indicated that the ability of the bladder to maintain a contraction and empty may be directly related to aerobic metabolism. Therefore, the decrease in aerobic metabolism (even in the presence of increased anaerobic metabolism) may in part explain the decreased ability of the obstructed bladder to empty. PMID- 2107339 TI - Blood bank officials hope donor altruism will pass new (anti-HCV) test. PMID- 2107340 TI - High-tech medicine and rising health care costs. PMID- 2107341 TI - Helmets for child bicyclists. PMID- 2107342 TI - [Effectiveness of antilymphocyte and antithymocyte globulins for patients with severe aplastic anemia and pure red cell aplasia--analysis of immunologic parameters of peripheral lymphocytes concerning ALG and ATG therapy]. AB - Four patients with severe aplastic anemia and one patient with pure red cell aplasia (PRCA) were treated with antilymphocyte and antithymocyte globulins. One patient in aplastic anemia who achieved good response by ALG administration had a possible diagnosis of myelodysplastic syndrome. ATG was administered to only one case of aplastic anemia and ALG was administered to the remainder. In the result, three out of 4 patients with aplastic anemia and one patient with PRCA achieved good response without severe side effects. Three patients with aplastic anemia had high CD4/CD8 ratio in their peripheral lymphocytes. This ratio normalized after ALG therapy in effective cases, but not in ineffective case. Natural killer activity elevated after ALG therapy in two effective cases of aplastic anemia and PRCA, but not in one ineffective case of aplastic anemia. PMID- 2107343 TI - [Clinical, cytogenetic and immunological studies of 2 cases with B-cell acute lymphocytic leukemia. Comparison between B-ALL and Burkitt's lymphoma reported in Japan]. AB - Two patients with acute lymphocytic leukemia of B-cell phenotype (B-ALL) are described. They were 77-year-old female and 34-year-old male. One patient presented with marked splenomegaly, and the other with rupture of spleen on admission. Leukemic morphology revealed a typical L3 profile by FAB classification system in both cases. Immunologic analysis showed the presence of surface immunoglobulins in both cases, and one phenotype was IgM kappa, whereas the other was IgG kappa. Cytogenetic study revealed the typical translocations (8; 14) in both cases. Following chemotherapy, complete remission was achieved in one case, but the other died 36 days after admission. Including our two cases, we studied 12 cases of B-ALL and 77 cases of Burkitt's lymphoma reported in Japan, investigating the clinical prognosis as well as the biological features. We concluded that there are no significant difference of survival between B-ALL and Burkitt's lymphoma. We estimated it is due to oncogenesis from the same original cell in despite of the difference in main tumor site between two diseases. PMID- 2107344 TI - [Autoimmune hemolytic anemia due to anti-e autoantibody of IgM class-report of a case]. AB - A 83-year-old woman, complaining of jaundice and anemia, was diagnosed as autoimmune hemolytic anemia (AIHA) with bilirubin gall stones. Her red blood cell (RBC) group was A, Rh (D) +, but the details were indefinite due to transfusions previously repeated, while anti-C3d serum reacted positively in the direct antiglobulin test. Her serum reacted with RBC other than R2R2 in the albumin (37 degrees C) method and in the bromelin method, the reaction turning out negative after the pretreatment with 2ME. These findings indicated the autoantibody was anti-e of IgM class, which had been so far rarely reported in Japan. PMID- 2107345 TI - [Temperature-dependent pseudoleukocytopenia and in vitro studies on the underlying mechanism]. AB - Spuriously low electronic white-cell count was obtained on EDTA-anticoagulated blood from a 54-year-old male suffering from liver cell carcinoma. In an attempt to understand better the phenomenon, in vitro studies were performed. The blood smear anticoagulated with EDTA revealed remarkable agglutinations of leukocytes, mainly neutrophils but not lymphocytes. The EDTA-treated blood showed maximal leukocytes-agglutinations at room temperature but no agglutination at 37 degrees C. The agglutinated leukocytes, moreover, were dispersed by incubating the blood at 37 degrees C. Although agglutination occurred in some degree in the blood anticoagulated with Na-heparin or Na3-citrate, it was much less pronounced compared to the EDTA-treated blood. Remarkable leukocytes-agglutinations were induced when EDTA-anticoagulated blood from healthy donor was mixed with serum from the patient at room temperature. These results suggest that the phenomenon of in vitro leukocyte agglutination and consequent pseudoleukocytopenia is due to leukocyte agglutinin in serum from the patient. The mechanisms were discussed comparing with pseudothrombocytopenia caused by platelet agglutinin. PMID- 2107346 TI - [Idiopathic thrombocytopenic purpura complicated with circulating lupus anticoagulant]. AB - A 37 year-old female was admitted to our hospital because of hypermenorrhea, prolonged bleeding time, thrombocytopenia and the diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Though activated partial thromboplastin time (APTT) was markedly prolonged, her coagulation factors were within normal ranges. Activities of the circulating lupus anticoagulant (LAC) was suggested. Kaolin clotting time of the platelet poor plasma was used as a sensitive screening test using the mixture of normal and patient's plasma for the detect of LAC. As a result, LAC positive pattern was observed. The treatment with high-dose gammaglobulin brought out a transient increase of the platelet count, but the prolongation of APTT was not corrected. Both the platelet count and the prolongation of APTT were significantly improved after the treatment with betamethasone. PMID- 2107347 TI - [Diverse hemostatic abnormalities in a patient with biclonal multiple myeloma]. AB - A 58-year-old female was referred to us because of M-proteinemia and anemia. Bone marrow showed normal cellularity with 14.8% of atypical plasma cells. Serum electrophoresis on cellulose acetate membrane revealed a single M-peak (56.9%). Immunoelectrophoresis showed large M-bows against anti-IgA and anti-lambda, together with small M-bows against anti-IgG and anti-kappa of the same electrophoretic mobility. In the urine, lambda type Bence Jones protein was found. The skull X-ray showed multiple punched out lesions. APTT was 61 seconds, fibrinogen 118 mg/dl, factor VIII clotting activity 25% with normal factor VIII related antigen, and factor IX clotting activity 38%. Circulating anticoagulants were not detected. These hemostatic abnormalities were thought ascribable to the interference of clotting activities by paraproteins. On the 33rd hospital day, she suffered from intracerebral hemorrhage, which was possibly due to these hemostatic abnormalities. PMID- 2107348 TI - Determination of bicarbonate output using pH deflection in the rat duodenum: influences of prostaglandins and cholinergic agents. AB - We set up a system to measure the luminal pH, potential difference (PD) and bicarbonate output in the anesthetized rat duodenum, and investigated these responses caused by prostaglandins (PGs) and cholinergic agents. When the proximal duodenum (1.7 cm) was perfused at a flow rate of 0.7 ml/min with saline adjusted to pH 4.5, the duodenal pH, PD and HCO3- output were 5.5 to 6.0, -4 to 6 mV and 1.2 to 1.6 muEq/10 min, respectively; they were markedly reduced by i.v. injection of saturated KCl. Both natural (PGE1, PGE2) and synthetic (PGE2, PGl2) PGs, given either s.c. or i.v., significantly elevated all these parameters, while indomethacin (s.c.) decreased the pH as well as the PD. Small but significant increases of the pH were observed after i.v. administration of cholinergic agents (carbachol, bethanechol), a GABAergic agent (baclofen) and an analogue of thyrotropin releasing hormone (YM-14673), with a temporal elevation of the PD; the degree of net HCO3- output caused by these agents was 20-50% of the values obtained with PGE2 (100 micrograms/kg, i.v.), and they were significantly reduced in the presence of atropine. These results suggest that (a) the system using pH deflections can be used to sensitively detect HCO3- output in the rat duodenum, and (b) duodenal acid neutralizing capacity may be regulated by central and peripheral cholinergic systems as well as endogenous PGs. PMID- 2107349 TI - Induction of liver microsomal UDP-glucuronyltransferase in the rat administered with a plant phenol, eugenol. AB - UDP-glucuronyltransferase activity toward xenobiotics in rat liver microsomes was increased about 2.6-fold by administration of a eugenol (4-allyl-2 methoxyphenol). Km value of the induced enzyme toward UDP-glucuronic acid, however, did not change. Immunoblotting analysis revealed that the amount of UDP glucuronyltransferase protein was increased in the microsomes of eugenol-treated rat liver. In vitro translation assay showed that the level of translatable mRNA encoding this enzyme increased in the liver. These results indicate that mRNA specific for production of UDP-glucuronyltransferase has accumulated, presumably by de novo synthesis in response to a plant phenol, eugenol. PMID- 2107350 TI - Serological and morphological observation on the outer membrane of Bacteroides succinogenes. PMID- 2107351 TI - Infection rates of Theileria sergenti in Haemaphysalis longicornis ticks collected from the field in Japan. AB - For a period of one year Haemaphysalis longicornis ticks were collected in a pasture from vegetation by dragging flannel cloth and from soil samples at monthly intervals. Nymphal ticks were assessed for Theileria infection. Salivary glands were stained with methylgreen-pyronin and examined for parasite masses. Nymphal H. longicornis infected with Theileria sergenti were found in all samples during 12 months including the winter. After shortening the prefed period on rabbits to 24 hours, the parasite masses could be detected in the salivary glands of nymphs collected in the grazing season, from May to October, while no parasite masses were detected in other season. It was suggested that the environmental factors in the grazing season might influence on the maturation of parasites in the salivary glands of ticks. PMID- 2107352 TI - [How to recover live mycobacteria from smear-positive and culture-negative specimens of mycobacteriosis patients]. AB - There are two kinds of smear-positive and culture-negative (SPCN) cases. One takes place temporarily when patients are under healing process and another takes place fro a long period of time. In the latter situation, probability of detecting live mycobacteria in the SPCN specimens seems to be high. To detect live mycobacteria, we examined 27 specimens which had been designated as SPCN previously, and could recover colonies from 14 specimens. Ten strains of M. tuberculosis and 4 strains of M. chelonae were identified. We analyzed factors of false results of SPCN specimens in routine examination. Nine out of 10 strains of M. tuberculosis were multi-drug resistant, and most of these strains were inhibited their growth on the media by added glycerol. Therefore we concluded that glycerol affected the proliferation of M. tuberculosis in SPCN specimens. Moreover, treatment of specimens by NaOH also affected the growth of mycobacteria. The number of colony which we recovered, decreased dramatically after the treatment by 4% NaOH (M. tuberculosis) and by 1% NaOH (M> chelonae). PMID- 2107353 TI - Monokines and platelet-derived growth factor modulate prostanoid production in growth arrested, human mesangial cells. AB - Previous studies have demonstrated considerable prostanoid production by cultured proliferating rat mesangial cells (MC). In this study, human mesangial cells (HMC) were examined during serum-free culture in which the cells were reversibly growth arrested and did not suffer obvious irreversible functional changes. Non stimulated cells released 2 to 10 pg/24 hr/micrograms cellular protein of PGE2, PGF2 alpha, 6-keto-PGF1 alpha, while TXB2 was not detectable. Stimulation with interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) induced up to 18-fold (IL-1 beta) or up to fourfold (TNF alpha) increases of prostanoid release. Combinations of the two monokines resulted in significant synergistic induction of PGE2 and 6-keto-PGF1 alpha up to 38 times that of control cells. Interleukin-6 (IL-6) and the HMC-mitogen, platelet-derived growth factor-BB (PDGF BB) only induced marginal increases in HMC prostanoid generation. However, when PDGF-BB or -AB was combined with IL-1 beta or IL-6, prostanoid generation by HMC was synergistically increased up to 222-fold (IL-1 beta) or 12-fold (IL-6) above the control values, with the induction of PGE2 greater than 6-keto-PGF1 alpha greater than PGF2 alpha much greater than TXB2. In the case of IL-1 beta + PDGF BB the induction of PGE2 release was at least partly due to the synergistic induction of cyclooxygenase activity. These findings demonstrate that both proliferating and reversibly growth arrested HMCs release prostaglandins in response to various inflammatory stimulators and combinations thereof. The findings support the important role of HMC in the regulation of glomerular hemodynamics during inflammatory processes. PMID- 2107354 TI - [A new treatment concept for severe caustic and thermal burns of the eyes]. AB - Combined surgical and drug therapy has proved efficacious in the treatment of severe eye burns. Initially, necrotic epibulbar tissue is excised. The sclera, denuded over a large area and in many cases ischemic, is covered with tenon flaps, prepared and advanced from the undamaged parabulbar connective tissue. For several months, artificial epithelium is used to protect the denuded and to a large extent acellular corneal stroma. Subsequently drug therapy, including corticosteroids, Healon, and prostaglandin synthesis inhibitors, is instituted to reduce the inflammatory reaction of the burned anterior segment. Regeneration of the conjunctival and later also the corneal epithelia may be improved by epidermal growth factor, autologous fibronectin, and proteinase inhibitors (Trasylol). This therapy avoids some complications which could not previously be influenced, and creates more favorable conditions for later corneal grafts. PMID- 2107355 TI - [Pericardial tamponade as a complication of the use of peripheral percutaneous silastic catheters]. AB - We report on two cases of cardiac tamponade by pericardial infusion in premature infants. In both infants an infusion was given via a Silastic central venous catheter. Because of the cardiac tamponade resuscitation and pericardiocentesis had to be performed. Both infants survived this serious complication of a central venous catheter. PMID- 2107356 TI - Diffuse esophageal intramural pseudodiverticulosis and nutcracker esophagus in a 54-year-old man. AB - Esophageal intramural pseudodiverticulosis, which was first described by Mendl et al. in 1960, is characterized by multiple small flask-shaped outpouchings in the esophageal wall. The pseudodiverticula represent dilated excretory ducts of deep mucous glands in the esophagus. The etiology of this rare condition is unknown. Hiatal hernias, gastroesophageal reflux, esophageal strictures, candida esophagitis, herpes esophagitis, diabetes mellitus, and chronic alcoholism have been found associated with intramural pseudodiverticulosis. We report the second case of esophageal hypermotility in intramural pseudodiverticulosis. PMID- 2107358 TI - [Draft: legislation on occupations in geriatric nursing. (Geriatric nursing legislation), 4 December 1989]. PMID- 2107357 TI - [2 year interferon therapy of metastatic carcinoid tumor]. AB - A 39 year old male patient was treated with daily 5 X 10(6) IU interferon alpha 2b s.c. for 22 months because of advanced carcinoid tumor. Objective response was achieved with greater than 50% reduction of 5-HIAA-excretion. Multiple metastases (liver, lung, bones, thyroid gland) were not progressing in size. An unintentional omission of treatment resulted in a rapid biochemical and morphological tumor progression. Reversibility was achieved with reinstitution of effective interferon therapy. Thus, interferon therapy of advanced carcinoid tumor is able to induce a long-term objective response. It seems to be superior to conventional chemotherapy. PMID- 2107359 TI - [Position of the German Nursing Federation regarding the 1st draft of 4 December 1989 of the legislation for occupations in geriatric nursing (geriatric nursing legislation)]. PMID- 2107360 TI - [What is kinesthetics in nursing?]. PMID- 2107361 TI - [Bandages and dressings--traditional nursing methods newly tested]. PMID- 2107362 TI - [Health promoting surroundings--color--shape--architecture]. PMID- 2107363 TI - [Holistic nursing--what is it, what can it accomplish?]. PMID- 2107364 TI - [Education, professional activity and perspectives in geriatric nursing (status in spring 1989)]. PMID- 2107365 TI - [Ethical and pastoral viewpoints in front of the necessary change in paradigms in medicine and nursing]. PMID- 2107366 TI - [Current activities "For tomorrow's care"]. PMID- 2107368 TI - Philadelphia chromosome-negative acute hematopoietic malignancy: ultrastructural, cytochemical and immunocytochemical evidence of mast cell and basophil differentiation. AB - We describe a patient with fever and multiple osteolytic bone lesions accompanied by hypercalcemia, a duodenal ulcer, anemia, and thrombocytopenia. Bone marrow showed a dense infiltration by abnormal cells characterized by small basophil granula, erythrophagocytosis and nuclear atypia. These cells were positive for toluidine blue and partly for myeloperoxidase and chloroacetate esterase, expressed myeloid differentiation markers, and exhibited multiple numerical and structural chromosome aberrations. Molecular genetic analysis showed no breakpoint cluster region rearrangement. Electron microscopy demonstrated granula both of basophil and mast cell type. Concluding, in this patient an acute hematopoietic malignancy with many features of malignant mastocytosis but also with signs of a basophil differentiation. This is further support for a hematopoietic stem cell origin of human mast cells. PMID- 2107367 TI - Comparative study of human and rat mammary tumorigenesis. PMID- 2107369 TI - GRF-induced GH response in attention-deficit hyperactivity disorder. AB - Attention-deficit hyperactivity disorder (ADHD) is a type of disruptive behavior of unknown etiology with a prevalence of 2.5-5% in school-age children. The useful evaluation of the GRF-induced GH response as a marker in some mental disorders led us to study the response of GH to the exogenous administration of GRF (1-29) NH2 (150 micrograms, i.v.) in ADHD children (N = 12, age = 7.78 +/- 1.66 years) and healthy children (N = 6; age = 8.73 +/- 2.24 years) in order to evaluate the functioning of the somatotropinergic system (GRF-SS-GH-SM axis) and using this neuroendocrine test as a potential diagnostic marker and/or a therapeutic predictor in ADHD. While controls (CS) showed a maximum GH response to GRF 15 min after injection (37.15 +/- 29.56 ng/ml; basal GH = 5.49 +/- 4.71 ng/ml), ADHD children (basal GH = 2.28 +/- 1.66 ng/ml) exhibited a lower response with a plateau from 15 (21.32 +/- 10.00 ng/ml) to 60 min (26.48 +/- 23.72 ng/ml). Serum GH levels at 90 (17.23 +/- 14.45 vs. 5.99 +/- 2.82 ng/ml, p less than 0.05) and 120 min (11.89 +/- 8.63 vs. 4.12 +/- 1.66 ng/ml, p less than 0.05) were significantly higher in ADHD than in CS. According to the GRF-induced GH response elicited in ADHD, two different populations of patients can be distinguished; one group with high response of GH (AUC = 3372.21 +/- 1127.61 ng.min/ml) and another group with a hyporeactive GH (AUC = 1567.46 +/- 726.0 ng.min/ml, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107370 TI - [Campylobacter (Helicobacter) pylori-induced cost effectiveness-risk considerations]. PMID- 2107371 TI - [Effectiveness, quality and economic aspects]. PMID- 2107372 TI - Preparation of extracts from prokaryotes. PMID- 2107373 TI - The private life of DNA polymerase I. PMID- 2107374 TI - Improving Michigan's health care system: beyond cost containment to serving patients' needs. PMID- 2107375 TI - Ten years of diabetic ketoacidosis. PMID- 2107376 TI - Minnesota OSHA infectious agent requirements. PMID- 2107377 TI - Raising Kane about the elderly. Interview by Richard L. Reece. PMID- 2107378 TI - Postoperative jejunal feedings following complicated pancreatitis. AB - Some surgeons avoid placing a jejunostomy in patients with complications, fearing either exacerbation of the disease during enteral feedings or complications from the jejunostomies. Eleven patients with hemorrhagic pancreatitis (four), pancreatic abscess (five), or infected pseudocyst (two) underwent placements of needle (five) or Red Robinson (six) jejunal catheters during laparotomy. Five patients had been given 30.8 +/- 16 liters of TPN over 25 +/- 12 days preoperatively. Only two patients received TPN postoperatively because of progressive sepsis with enteral intolerance to feedings. One of these patients developed a jejunal leak near the placement of the Red Robinson catheter. Both patients died of complications from their pancreatic disease. The remaining nine patients received 35.6 +/- 8.6 liters of enteral feedings over 31 +/- 6.8 days before resuming oral intake. Glucosuria and hyperglycemia were common, but easily managed. No catheters were lost, and diarrhea necessitating slowing and diluting the diet was unusual after the first week. Enteral feeding did not elevate amylase values. Therefore, jejunal feedings can be given safely in patients with severe acute pancreatic disease to provide prolonged nutrition without aggravating the disease. PMID- 2107379 TI - Parenteral nutrition in a bone marrow transplant patient with hepatic complications. PMID- 2107380 TI - Managing the complications associated with refeeding. PMID- 2107381 TI - Calculation for dilution of enteral diets. PMID- 2107382 TI - Mortality patterns--United States, 1987. PMID- 2107383 TI - Bovine tuberculosis--Pennsylvania. PMID- 2107384 TI - Rabies in a llama--Oklahoma. PMID- 2107385 TI - Mortality in developed countries. PMID- 2107386 TI - International Task Force for Disease Eradication. PMID- 2107387 TI - World No-Tobacco Day. PMID- 2107388 TI - Update: filovirus infection in animal handlers. PMID- 2107389 TI - [Subrenal capsule assay in normal mice immunosuppressed by cyclosporin A]. AB - The subrenal capsule assay in normal mice has more advantages to evaluate sensitivities of anticancer agents than other assays in vivo. However, this method has difficulties because mice reject human tumor grafts by their immune reaction. We examined three methods of immunosuppression in mice; radiation, administration of cyclophosphamide and that of cyclosporin A. The administration of cyclosporin A suppressed host reactions most effectively among the three, and the human tumor grafts in subrenal capsules grew well. We also investigated the intervals of administration and the doses of cyclosporin A in order to evaluate drug response. The minimal dose of cyclosporin A which inhibited host reactions was revealed to be 50mg/kg/day administered subcutaneously to mice. Then the adequate dosage of each anticancer drug for this assay system was investigated so that the body weights of mice do not decrease more than 20%, and the following doses were determined; Mitomycin C: 5mg/kg; Cisplatinum: 4mg/kg; Cyclophosphamide: 100mg/kg and 5FU: 90 mg/kg. PMID- 2107390 TI - Ethanol withdrawal seizures produce increased c-fos mRNA in mouse brain. AB - mRNA levels for the protooncogene c-fos, measured by Northern blot analysis, were greatly increased in brains of mice undergoing ethanol withdrawal seizures. This increase was transient (levels were increased at the time of the seizure and returned to normal by 24 hr or less after seizure) and was larger in hippocampus (40-fold) than in cerebral cortex (10-fold) or in cerebellum (6-fold). In mice that were fed ethanol chronically and withdrawn but that did not undergo overt withdrawal seizures, c-fos mRNA levels were not significantly increased. The findings with ethanol withdrawal seizures are similar in many respects to results of earlier studies with chemically induced seizures or kindling, which had led to the suggestion that c-fos expression may play a role in neuronal adaptation. The development of ethanol withdrawal seizures has been likened to kindling, and there is evidence indicating that ethanol withdrawal symptoms become more severe after repeated episodes of withdrawal. The present data support the hypothesis that this phenomenon may involve ethanol withdrawal seizure-induced increases in c-fos expression in various brain areas. PMID- 2107391 TI - Mechanism of the reaction of ebselen with endogenous thiols: dihydrolipoate is a better cofactor than glutathione in the peroxidase activity of ebselen. AB - The therapeutic effect of ebselen has been linked to its peroxidase activity. In the present study, the peroxidase activity of ebselen toward H2O2 with the endogenous thiols GSH and dihydrolipoate [L(SH)2] as cofactors was determined. When GSH was used, peroxide removal was described by a ter uni ping pong mechanism with Dalziel coefficients for GSH and H2O2 of 0.165 +/- 0.011 and 0.081 +/- 0.005 mM min, respectively. When L(SH)2 was used, peroxidase activity was independent of the concentration of L(SH)2 in the concentration range studied (5 microM to 2 mM) and peroxide removal was only dependent on the concentration of H2O2 and ebselen, with the second-order rate constant being 12.3 +/- 0.8 mM-1 min 1. To elucidate the difference between GSH and L(SH)2, the molecular mechanism of the peroxidase activity of ebselen was investigated, using UV spectrophotometry, high pressure liquid chromatography, 77Se NMR, and mass spectrometry. GSH was found to react quickly with ebselen to give a selenenyl sulfide, an adduct of GSH to ebselen. Subsequently, the GSH-selenenyl sulfide is converted into the diselenide of ebselen. Finally the diselenide reacts with a peroxide and ebselen is regenerated. The formation by GSH of the diselenide from the GSH-selenenyl sulfide of ebselen is slow and linearly dependent on the concentration of free thiol; however, no net consumption of GSH was observed. Furthermore, it is likely that a selenol is an intermediate in diselenide formation. After reaction between ebselen and L(SH)2 the diselenide of ebselen was immediately detected. The fast formation of the diselenide with L(SH)2 versus the slow formation of the diselenide with GSH accounts for our observation that L(SH)2 is a better cofactor than GSH in the peroxidase activity of ebselen. Our results suggest that the interaction between ebselen and L(SH)2 might be of major importance in the mechanism by which ebselen exerts its therapeutic effect. PMID- 2107392 TI - Sequence analysis of homogeneous peptides of shark immunoglobulin light chains by tandem mass spectrometry: correlation with gene sequence and homologies among variable and constant region peptides of sharks and mammals. AB - Morphologically, sharks are living fossils that are remarkably similar to their Devonian ancestors of ca. 400 million years ago. If a parallel conservation in biochemical properties characterizes shark evolution, knowledge of the properties of shark immunoglobulins should provide information on the structure of primordial immunoglobulins and their genes. The problem of polyclonality of shark immunoglobulins has precluded detailed analysis of shark immunoglobulin light polypeptide chains. Here, we approach the problem of obtaining direct sequence information on polyclonal light chains of shark immunoglobulins by isolating homogeneous peptides from tryptic digests of shark light chains and sequencing these by tandem mass spectrometry. To confirm the location of the peptides, we isolated a complementary DNA (cDNA) clone from a sandbar shark cDNA library in the expression vector lambda gt11, identifying the clone by its ability to produce a peptide serologically detectable using rabbit antibody to purified shark light chain. The correspondence between peptide sequence and that derived from gene sequence provided direct proof that the gene studied was that of a major expressed serum light chain. Using this combined approach, we isolated homogeneous peptides from both constant and variable regions. The variable region peptides showed homology to corresponding sequences of mammalian V lambda and V kappa sequences. The constant region gene sequence we obtained was homologous to mammalian C lambda sequence. The four constant region tryptic peptides we sequenced corresponded exactly to stretches of the C lambda sequence derived from the DNA sequence. The combined approach described here shows that shark light chains exhibit heterogeneity at both the protein and gene level, but that the constant regions of these chains can be identified as homologs of mammalian lambda chains and that evolutionary conservation has occurred in V region sequences ranging from elasmobranchs to man. PMID- 2107393 TI - Bacterial expression of immunoglobulin VH proteins. AB - A bacterial expression system in Escherichia coli has been developed that produces as much as 10 mg/l of culture of the VH protein associated with monoclonal antibodies specific for the 5-dimethylaminonaphthalene-2-sulfonyl (Dns) group. This system has been applied to the expression of the VH genes derived from a low-affinity, IgM-producing hybridoma and from a high-affinity, IgG-producing cell line. The plasmid vectors (contributed by Dr William F. Studier) utilize a T7 expression cassette whose activity is initiated by infection with a lambda phage derivative carrying the T7 RNA polymerase gene. The VH proteins were extracted from the bacterial pellet in 8 M urea and purified by chromatography in 8 M urea. Recombinants with the homologous light (L) chains were prepared to yield VHL molecules. These were used to measure intrinsic affinity for Dns-lysine by resonance energy transfer. The association constants were 7 x 10(6) M-1 and 7 x 10(9) M-1 for the low- and high-affinity systems, respectively. These values are not significantly different from those observed with monoclonal antibodies secreted from the corresponding cell lines. This system lends itself to the quantitative evaluation of the binding properties of the VH protein itself as well as the modulation of affinity by site-directed mutagenesis. PMID- 2107394 TI - The incidence of a new human cross-reactive idiotype linked to subgroup VHIII heavy chains. AB - Cross-reactive idiotypes (CRI) on human rheumatoid factors (RF), which are identified by murine monoclonal antibodies (mAb), have proved useful in defining both the incidence and the structural characteristics of these autoantibodies. In this study, a new murine anti-idiotypic reagent, mAb B6, has been used to identify and define the expression of a distinct heavy chain CRI. The B6 CRI was found on 20% of monoclonal IgM (16 of 81), but on only 5% of monoclonal IgA (1 of 20) and on no monoclonal IgG. In addition, this CRI was expressed exclusively on a subset of Ig derived from the VHIII protein variable region subgroup. In immunoblotting experiments, the mAb B6 bound directly to the heavy (H) chains of CRI positive proteins. The B6 CRI was found frequently on monoclonal IgM-RF molecules, and the mAb B6 could inhibit the binding of the RF to its IgG antigen. It was also demonstrated that Staphylococcus aureus protein A (SpA), which has recently been shown to bind to the F(ab) region of VHIII molecules, could block the interaction of some B6 CRI positive IgM to the anti-CRI. These experiments suggest that the B6 CRI is a marker for one or a few VHIII genes and that it is expressed commonly on IgM paraproteins, many of which have RF activity. PMID- 2107395 TI - Evaluation of different hybridization procedures for the detection of mycoplasma contamination in cell cultures. AB - Cell culture samples were analysed for mycoplasma contaminations with two different DNA probes which have been described earlier. One probe (the H900 probe), derived from the 23S rRNA gene of Mycoplasma hyorhinis, cross-hybridized with virtually all mycoplasmas (including the acholeplasmas). The other probe (the T2 probe), derived from a protein gene of Acholeplasma laidlawii, cross hybridized with most acholeplasmas. The two probes were compared in three different direct filter hybridization procedures without previous isolation of DNA or RNA. One of the procedures, developed in the present study, gave the highest sensitivity in DNA-RNA hybridization but also worked satisfactorily in DNA-DNA hybridization. The sensitivity of the H900 probe in filter hybridization experiments was compared with the sensitivity of a commercial probe for detection of mycoplasma contaminations in cell cultures. The H900 probe was found to be at least 25 times more sensitive for all cell culture mycoplasmas except for A. laidlawii, for which they were equally sensitive. PMID- 2107396 TI - [Long-term experiences with central venous catheters in pediatric oncology]. AB - 93 central venous catheters (77 Broviac und 16 ports) were inserted in 79 children with malignant diseases between 1980 and 1988. The median duration of use for Broviac was 5.8 months (0.2-24 months) and for ports 7.5 months (0.8-44 months). The total duration of use was 14 658 days for Broviac catheters and 5970 days for ports. The most frequent complications were dislogements, obstructions and infections. They were observed in 19 out of 77 Broviac catheters (25%) and in 5 out of 16 ports (31%). Because of complications 17 out of 93 catheters were prematurely removed. Complication rates were not significantly different in both systems. The incidence of infections in Broviac catheters was 5% or 0.27 per 1000 days of use, respectively, which is lower than reported by other studies. The consistency in catheter-care procedures can decrease the rates of complications. PMID- 2107397 TI - [Hypoplasia of the nails and end phalanges as a sequela of prenatal barbiturate exposure]. AB - We describe a case of a Turkish boy with features of hydantoin-barbiturate embryopathy. Main symptoms are hypoplasia, partly aplasia, of the finger- and toenails as well as the distal phalanges. His epileptic mother was treated with phenobarbiturates during the first three months of pregnancy. PMID- 2107398 TI - Induction of umu gene expression in Salmonella typhimurium TA1535/pSK1002 by dimethyl sulfoxide (DMSO). AB - The genotoxicity of dimethyl sulfoxide (DMSO) was demonstrated by the umu test using Salmonella typhimurium TA1535/pSK1002 carrying the umuC-lacZ fusion gene. The level of beta-galactosidase activity which shows umu gene expression in the test system was dependent on the concentration of DMSO in the culture medium. The maximum beta-galactosidase activity was approximately 3.5 times as high as the background level with 10% of DMSO in the culture medium. The lowest concentration of DMSO required for a response of over twice the background level was approximately 5%. Four structurally related chemicals (acetone, di-n butylsulfoxide, dimethylsulfide, methylphenylsulfoxide) did not show umu gene expression at their non-toxic doses. PMID- 2107399 TI - Rat and human Schwann cells in vitro can synthesize and express MHC molecules. AB - The expression of MHC class I and II molecules on cultured rat and human Schwann cells (SCs) was studied to determine whether these molecules could be synthesized by SCs in the absence of T cells. Normal rat and human SCs in vitro expressed low levels of class I MHC, but this was markedly increased by incubation with interferon gamma (IFN-gamma). Untreated SCs of rat or human origin did not express detectable class II MHC molecules, but after 48 hours incubation with IFN gamma 100 U/ml, 20% of rat SCs and 90% of human SCs were class II positive. Immunoelectron microscopy confirmed the surface expression of MHC molecules on SCs and demonstrated class II MHC within endocytotic vesicles. These findings provide further evidence for an immunological role for SCs as antigen presenting cells or as targets for cytotoxic T cells. PMID- 2107400 TI - Streptokinase equal to TPA. PMID- 2107401 TI - Gene expression. Chromatin contract to silence. PMID- 2107402 TI - Dependence of position-effect variegation in Drosophila on dose of a gene encoding an unusual zinc-finger protein. AB - Position-effect variegation is the inactivation in some cells of a gene translocated next to heterochromatin, the region of the chromosome that is permanently condensed. The number of copies of the Drosophila gene Suvar(3)7 is a dose-limiting factor in this phenomenon, and seems from its sequence that it encodes a protein with five widely spaced zinc-fingers. This novel arrangement of zinc-fingers could help in packaging the chromatin fibre into heterochromatin, and also reflect a novel method of controlling the expression from DNA domains. PMID- 2107403 TI - Homologous activators of ras in fission and budding yeast. AB - The ras proto-oncogene products are plasma membrane-bound, guanine nucleotide binding proteins implicated in signal transduction across the plasma membrane. But the signal(s) that activates the ras pathway(s) is not known. In the budding yeast Saccharomyces cerevisiae, the CDC25 gene product acts upstream of Ras proteins, but it has not been clear whether CDC25 function is unique to the S. cerevisiae ras pathway. Here we report that the ste6 gene of fission yeast Schizosaccharomyces pombe is a homologue of CDC25: the ste6 gene product and the CDC25 gene product have significant amino-acid similarity in their C-terminal regions. Like the S. pombe ras1 gene, ste6 is essential for mating. Epistatic interactions indicate that the ste6 gene functions upstream of ras1. We propose that ste6 and CDC25 activate Ras protein through a common mechanism, perhaps by promoting GDP-GTP exchange, even though it seems that the function of Ras protein in budding yeast differs from that in fission yeast. Homologues of ste6 and CDC25 could regulate ras activity in other eukaryotic cells. PMID- 2107404 TI - Intracerebroventricular treatment of mice with pertussis toxin induces hyperalgesia and enhances 3H-nitrendipine binding to synaptic membranes: similarity with morphine tolerance. AB - The effect of intracerebroventricular treatment of mice with pertussis toxin (PTX) on pain perception and 3H-nitrendipine binding was examined to study a possible change in the GTP-binding proteins in morphine tolerant rodents. It was observed that both PTX treatment and chronic administration of morphine cause hyperalgesia in the acetic acid-induced writhing test. Analgesic effects brought by the acute administration of morphine or nifedipine, a calcium antagonist, were not affected by PTX treatment. In synaptic membrane fractions prepared from mice treated with PTX or morphine chronically, specific binding of 3H-nitrendipine was enhanced approximately 41.8% and 35.7%, respectively, without alteration in its affinity. Chronic administration of morphine followed by PTX treatment did not display further increases in 3H-nitrendipine binding. These results suggest that the PTX-sensitive GTP-binding proteins may not be involved in the manifestation of the analgesic effect of morphine in mice. PMID- 2107405 TI - [The role of drugs in the treatment of obsessive-compulsive disorders]. PMID- 2107406 TI - Community survival. PMID- 2107407 TI - Education: a circle of care. The 1989 Kathleen A Raven nursing lecture. PMID- 2107408 TI - School nursing: health appraisal pilot study. PMID- 2107410 TI - Theatre nursing: making the most of theatre allocation. PMID- 2107409 TI - Helping to prevent accidents in the home. PMID- 2107411 TI - Children and pain. PMID- 2107412 TI - Life and death--the moral dilemmas facing nurses. PMID- 2107413 TI - Responding to rights. PMID- 2107414 TI - Taking centre stage. Interview by Jean Gray. PMID- 2107415 TI - Nursing homes. Setting up a residential home. Interview by Charlotte Alderman. PMID- 2107417 TI - NHS Bill: amending, not making do. PMID- 2107416 TI - The penalty of success. Interview by Jean Gray. PMID- 2107418 TI - Class of '88: halfway there. PMID- 2107419 TI - Massage therapy and nursing care. PMID- 2107420 TI - Psychodynamic thinking in nursing practice. PMID- 2107421 TI - Treating the victims of rape. PMID- 2107423 TI - A new beginning. Interview by Julie Sylvester. PMID- 2107422 TI - Health promotion: Project 2000 and the specialist practitioner. PMID- 2107424 TI - AIDS focus. PMID- 2107425 TI - AIDS focus. A positive ACET. PMID- 2107426 TI - AIDS focus. AIDS and the law. PMID- 2107427 TI - The Edenbrook experience. PMID- 2107429 TI - Recruitment: teenage troubles. PMID- 2107428 TI - Professional misconduct: a long wait for justice. PMID- 2107430 TI - Mouthcare in oral cavity cancer. PMID- 2107431 TI - AIDS: the fear of contagion. PMID- 2107432 TI - Evaluation of patient satisfaction in A&E. PMID- 2107433 TI - Evaluating bodyworn continence pads. PMID- 2107434 TI - Ethical issues--making life and death decisions. PMID- 2107436 TI - Nurses and transport. PMID- 2107435 TI - Keeping abreast of the times. PMID- 2107437 TI - Nurses and transport. Claiming car benefits. PMID- 2107438 TI - Nurses and travel. Travelling hopefully. PMID- 2107440 TI - Nurses' pay: a stage-managed award. PMID- 2107439 TI - The White Paper and nursing. PMID- 2107441 TI - Stress management--'the group approach'. PMID- 2107442 TI - Cancer care: a two way process. PMID- 2107443 TI - Quality assurance--a positive approach. PMID- 2107444 TI - Project 2000: the reflective practitioner--is help at hand? PMID- 2107445 TI - Failure to fail: the teacher's dilemma. PMID- 2107447 TI - Organising professionally. PMID- 2107446 TI - School nursing and standards of care. PMID- 2107448 TI - Training for a change. PMID- 2107450 TI - Uniform distress. PMID- 2107449 TI - Grandad goes to hospital. PMID- 2107451 TI - Uniforms. PMID- 2107452 TI - Uniforms. Dress sense. PMID- 2107453 TI - Uniforms. Professional identity. PMID- 2107455 TI - Does very preterm birth impair myelination of the central nervous system? AB - Myelination of the central nervous system (CNS) can be demonstrated with magnetic resonance (MR) imaging. Myelin formation may be reduced in conditions of neonatal "undernutrition". Very preterm infants have a reduced postnatal growth rate when compared with intrauterine fetuses of the same gestational age. Using MR imaging, we studied qualitative myelination patterns in healthy preterm infants of less than 30 weeks gestation with an optimal nutritional intake and in term infants at 44 weeks postmenstrual age (PMA). At that age, preterm infants had a significantly lower mean body weight than term infants, but mean head circumference did not differ significantly. All preterm and term infants had reached myelination stage M3 (myelin in brainstem, internal capsule, and corona radiata) and M4 (myelin in brainstem, internal capsule, corona radiata, and centrum semiovale). There was no significant difference in myelination stage between the preterm and term infants. We conclude that adequate nutrition in the neonatal period leads to qualitatively adequate myelination of the CNS in very preterm infants. PMID- 2107454 TI - Nonamyloidotic nephrotic syndrome in Waldenstrom's macroglobulinemia. AB - Severe nephrotic syndrome developed in an 83-year-old Japanese man with Waldenstrom's macroglobulinemia. Treatment with corticoid remarkably improved the proteinuria. Autopsy disclosed no deposit of amyloid in the kidneys but a slight infiltration of atypical lymphocytes. A considerable number of glomeruli showed mesangial cell proliferation and global or segmental thickening of the basement membrane with occasional double tracks. Immunofluorescent studies revealed deposits of IgM but not IgG, IgA and C3 along the basement membrane in most glomeruli. Electron microscopy disclosed the splitting glomerular basement membrane and scattered electron-dense deposits. PMID- 2107456 TI - L-carnitine replacement therapy in chronic valproate treatment. AB - Ten epileptic children with chronic valproic acid (VPA) treatment were given L carnitine for 14 days. As compared to age and sex matched control subjects the carnitine status of the VPA treated children showed carnitine insufficiency prior to the carnitine administration with lower total and free carnitine in plasma and in urine. In response to the extra intake the plasma free and esterified carnitines increased 1.7-fold. The daily excreted amount of esterified carnitines increased 6.5-fold (1.55 +/- 0.23 vs 10.1 +/- 1.68 mumol/kg/day, means +/- SEM, p less than 0.005) showing that a considerable part of the administered carnitine participated in the elimination of acyl groups from the body. The depressed level of beta-hydroxybutyrate in the plasma (31.8 +/- 7.42 vs controls 118.0 +/- 16.0 mumol/l, means +/- SEM, p less than 0.005) remained unaffected by the carnitine administration (29.7 +/- 7.06 mumol/l) suggesting that the hypoketonemia is not a direct consequence of the carnitine insufficiency. No differences were observed in the plasma level of free fatty acids, triglycerides and in insulin: glucagon ratios between the VPA treated and control subjects, suggesting that lipolysis of fats and the hepatic hormonal control mediated by these hormones are not the sites at which VPA causes reduced fasting ketogenesis. The plasma level of VPA and the seizure control remained unaffected by carnitine treatment. PMID- 2107457 TI - The relationship of working memory to the immediate recall of stories following unilateral temporal or frontal lobectomy. AB - Patients undergoing unilateral temporal lobectomy were tested preoperatively for working memory capacity, sentence comprehension, and rapid-naming ability, and were retested on these same measures 3 to 5 days and 2 weeks postoperatively. Immediate recall of stories was assessed twice only: preoperatively, and 2 weeks postoperatively. The left temporal-lobe group demonstrated transient deficits in working memory capacity, sentence comprehension, and rapid-naming ability over the 2 week postoperative period. No significant group differences in working memory capacity were evident two weeks after operation, even though the story recall of the left temporal-lobe group was impaired. A second experiment, with additional patients, explored the possible contribution of the hippocampus and of the frontal lobes to performance on these same tasks. Extent of hippocampal excision did not affect performance differentially on any task. Story recall was impaired following left temporal lobectomy, whereas left frontal lobectomy impaired sentence comprehension and rapid-naming ability. These results indicate a double dissociation of verbal deficits 2 weeks after left temporal- and left frontal-lobe excisions. PMID- 2107458 TI - Nonspatial conditional learning impaired in patients with unilateral frontal but not unilateral temporal lobe excisions. AB - The present study examined the effect of unilateral frontal- or temporal-lobe excisions on the acquisition of a conditional task requiring that the subjects respond to each one of six different coloured stimuli by selecting, from a set of six abstract designs, the correct design for each stimulus. Patients with excisions from the left or right frontal cortex were impaired in learning this task, whereas patients with left or right temporal-lobe excisions, with or without radical involvement of the hippocampal region, were not impaired. These findings demonstrate that the major role played by the frontal cortex in the acquisition of conditional responses is a general one and not restricted to situations involving different movements. PMID- 2107459 TI - Cocaine-induced seizures. AB - We retrospectively studied 474 patients seen at Hennepin County Medical Center because of medical complications related to acute cocaine intoxication. Of the 474, 403 had no history of seizures. Seizures within 90 minutes of cocaine use was the primary diagnosis in 32 (7.9%) of the 403. The majority of seizures were single, generalized, induced by intravenous or "crack" cocaine, and not associated with any lasting neurologic deficits. Most that were focal, multiple, or induced by nasal cocaine were associated with an acute intracerebral complication or concurrent use of other drugs. Of 71 patients with a history of non-cocaine-related seizures, 12 (16.9%) presented with cocaine-induced seizures; most of these were multiple, of the same type as those in their history, and induced by even nasal cocaine. In the 44 cocaine-induced seizure patients, a pattern of habitual cocaine abuse was associated with diffuse brain atrophy on CT and diffuse slowing on EEG. PMID- 2107460 TI - Sudden death in Air Force recruits. PMID- 2107461 TI - Excretion of morphine in urine following the ingestion of poppy seeds. PMID- 2107462 TI - Treating endogenous depression. PMID- 2107463 TI - Airborne tactical medical support in Grenada. AB - On October 24, 1983, clinical fillers rapidly integrated into the 82d Airborne Division, deployed to the Island of Grenada, and significantly contributed to the tactical medical support mission during Operation Urgent Fury. However, the medical community's unfamiliarity with the airborne division's operational requirements and the 307th Medical Battalion's capabilities have created questions which must be addressed to provide a clearer understanding of what occurred at the division level of medical support (DLMS) during the initial 4 days of the operation. This article outlines key aspects for DLMS to the U.S. Army airborne division and briefly reviews DLMS during Operation Urgent Fury. PMID- 2107464 TI - Travelers' diarrhea among U.S. Navy and Marine Corps personnel during a Western Pacific deployment. AB - The incidence and etiology of travelers' diarrhea was studied in a crew of 1,914 sailors and marines aboard a U.S. Navy ship during a western Pacific deployment. Questionnaires completed by 301 troops indicated that 52% had at least one episode of diarrhea during the deployment; however, only 5% of the ship's company sought treatment. Enterotoxigenic Escherichia coli was the most commonly identified pathogen (23%), followed by Giardia lamblia (6%), Salmonella (3%), rotavirus (2%), and Shigella, Campylobacter jejuni, and Entamoeba histolytica (1% each). In 66% of the episodes no etiologic agent was found. None of the risk factors thought to be associated with travelers' diarrhea could be statistically associated with the diarrhea group in comparison to questionnaire respondents who denied having had the illness. PMID- 2107465 TI - Exertion-induced heat stroke in a military setting. AB - Heat stroke is a medical emergency characterized by sudden loss of consciousness and by failure of the heat-regulating mechanism, as manifested by high fever (usually above 104 degrees F) and cessation of sweating. Fatality rates for patients with heat stroke can vary from 0% to more than 40%. Immediately after heat stroke has occurred or is suspected, aggressive cooling measures should be initiated. This case illustrates a 24-year-old commissioned officer who developed heat stroke while running in PT formation dressed with shorts and a T-shirt. Although this patient was in good shape and the wet bulb was only 74.4 degrees F, he developed the classic symptoms of heat stroke, with a core temperature of 105.9 degrees F. He further developed hepatic and skeletal muscle enzyme abnormalities (SGOT, 4680; CPK, 327; LDH, 821) with hyposphosphatemia (0.8). This patient had no significant risk factors, and after the appropriate treatment, his enzyme abnormalities returned to normal without sequelae. This paper will discuss symptoms, predisposing factors, complications, treatment, and prevention of heat stroke--a topic that is important to all military physicians, especially to those deployed to hot, humid environments. PMID- 2107466 TI - Fitness, performance and anthropometric characteristics of 19,185 Canadian Forces personnel classified according to body mass index. AB - The Canadian Forces (CF), concerned with the possible adverse effects of obesity on military performance and image, recently adopted the body mass index (BMI) to monitor excess weight among its personnel. Subsequently, the records of 17,098 CF men (32.0 +/- 8 years) and 2,087 CF women (26.2 +/- 5 years) were examined. Approximately 50% of the men and 25% of the women had a BMI greater than 25 kg/m2, while 26% of the men and 12% of the women had a BMI greater than 27 kg/m2. Except for grip strength, both men and women in higher BMI zones typically demonstrated significantly lower fitness and performance scores than those in lower BMI zones. For men and women, increasing BMI was associated with progressive and significant increases in body weight, chest girth, waist girth, gluteal girth, thigh girth, waist-to-hip ratio, and waist-to-height ratio, and decreases in difference between chest-minus-waist girths. Waist girth increased proportionately more than other circumferences with increasing BMI, thus indicating a greater relative deposition of body fat in the abdominal region. In view of the relationship between high BMI and compromised fitness, appearance, and health observed in this population, the CF would benefit from continued educational and clinical efforts to reduce the prevalence of obesity. The BMI would serve as a useful epidemiologic standard to help monitor progress in these areas. PMID- 2107467 TI - Personality factors in failure to adapt to the military. AB - As technical training costs increase in the military, it is increasingly important to identify and eliminate as soon as possible individuals unwilling or unable to adapt to the demands of the military. The present study compares three groups of enlisted personnel below the rank of E-4: a group having adjustment problems but motivated to remain in the military, a group having adjustment problems and seeking a discharge, and a well-adjusted group. Two scales of a personality inventory were found to differentiate the groups and suggest potential value for screening of military applicants. PMID- 2107468 TI - Burns in the Lebanon War 1982: "the blow and the cure". AB - There were 70% more burns in the October 1973 war than in the Six Day War of 1967. This increase caused great concern and emphasized the need for better personal and crew protection against burns. Some of these measures were already implemented by the outbreak of the 1982 war in Lebanon. Analysis of the burn injuries of this war is the subject of this short report. PMID- 2107469 TI - A comparison of drug products available in Germany and the United States. AB - Health-care professionals practicing with the U.S. European Command frequently encounter drug products of their host nation. Confusion about the identity or use of these medications can slow emergency treatment or mislead the medical management of patients. This article compares drug products available in the Federal Republic of Germany (FRG) with those of the United States of America. Differences in nomenclature used for generic drug names are described, as well as prescription practices unique to the FRG, such as unusual drug combinations, additional dosage forms, and divergent labeling practices. Military pharmacies are effective resources for translation of host nation drug products. PMID- 2107470 TI - Case for diagnosis. Necrotizing granulomatous cholangiohepatitis with multifocal caseonecrotic granulomas caused by Chlamydia psittaci organisms and a concomitant enteric infection. PMID- 2107471 TI - The deputy commander for clinical services. PMID- 2107472 TI - Is war surgery a specialty? Part I. AB - Since 1950 the peacetime practice of civilian and military surgery has shifted from general surgery to increasing specialization and subspecialization. The surgical management of war wounds continues to require a solid foundation in general surgery training and experience, plus additional specific training in wartime surgery. Even the trauma specialist will face significant differences and difficulties treating war wounds in field hospitals. Neither military nor civilian surgical programs provide this training. This two-part essay identified major characteristics of War Surgery and explores the essential training and education required to prepare civilian and military surgeons for the practice of war surgery. PMID- 2107473 TI - Dealing with the stress of an HIV-positive diagnosis at an Army medical center. AB - Following mandatory military-wide testing for the human immunodeficiency virus (HIV), Army medical facilities have gained extensive experience with HIV-positive persons who undergo special stresses as a result of their affiliation with the military. The consequences of evacuation to medical centers for evaluation of HIV status are presented and the impact of this process on the medical center staff are considered. This paper is a description of one system designed to evaluate, treat, and support HIV-positive soldiers and their families. PMID- 2107474 TI - Community nursing. Long-term urinary catheterisation. PMID- 2107475 TI - Controversy grows over parallel track for experimental AIDS drug. PMID- 2107476 TI - Rehabilitation cost effectiveness of stroke. PMID- 2107477 TI - Cost-efficient nursing research in clinical practice. PMID- 2107478 TI - Maternal and fetal catecholamines and uterine incision-to-delivery interval during elective cesarean. AB - The fetal sympathoadrenal system is activated during periods of intrauterine stress such as inadequate uterine perfusion. During cesarean, the period of interruption of utero-placental blood flow is extended as the time interval from uterine incision to delivery increases. An increasing uterine incision-to delivery interval with spinal or general anesthesia has been associated with a poorer neonatal outcome. This association has not been demonstrated previously in patients undergoing cesarean delivery under epidural anesthesia. We investigated the correlation between prolonged uterine incision-to-delivery intervals, fetal catecholamine concentrations, and fetal blood gas values at delivery in 25 parturients undergoing cesarean under epidural anesthesia and in 28 under spinal anesthesia. Infants delivered after prolonged uterine incision-to-delivery intervals had significantly lower pH values in both the epidural and spinal groups. With longer uterine incision-to-delivery intervals, umbilical arterial norepinephrine concentrations were increased significantly. Umbilical arterial pH values were significantly lower in infants with higher umbilical arterial catecholamine concentrations. The importance of minimizing the uterine incision to-delivery interval, regardless of the type of anesthetic selected, is demonstrated. PMID- 2107479 TI - Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies. AB - Maternal lupus anticoagulants and anticardiolipin antibodies are associated with a syndrome of recurrent pregnancy loss or preterm birth in live-borns, fetal growth retardation, and placental infarction. Fourteen women with one or more abnormal pregnancy outcomes (total 28 losses, one severely growth-retarded premature live-born) and no normal outcomes were treated with full-dose, subcutaneous, twice-daily heparin therapy in subsequent pregnancies. Treatment was started at an estimated gestational age of 10.3 +/- 4.0 (mean +/- SD) weeks (range 6-18), in a mean total daily dosage of 24,700 +/- 7400 units (range 10,000 36,000). Fourteen of 15 pregnancies resulted in live births at 36.1 +/- 1.7 weeks (range 33-39). The mean birth weight percentile was 57 +/- 21 (range 10-90), and Apgar scores were good to excellent. The number of placental infarcts was fewer in treated cases than in previous deliveries. Five fetuses had third-trimester or perinatal problems with no sequelae, four discovered by close maternal-fetal monitoring. There was an increased rate of preterm and cesarean deliveries. Maternal complications of treatment were few and minor, with no hypertension, preeclampsia, or serious drug-related complications. Heparin appears suitable for further investigation in the treatment of this obstetric syndrome. PMID- 2107480 TI - Long-term follow-up of patients with advanced ovarian carcinoma treated with debulking surgery and chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide. Gynecologic Oncology Group of the Comprehensive Cancer Center. AB - Between June 1980 and December 1984, 88 patients with stage III-IV ovarian carcinoma were entered in a study evaluating the role of debulking surgery and chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin intravenously on day 1, every 4 weeks (CAP-1). The results after a median follow up of 62 months (range 41-93 months) are presented. The median survival of all patients was 24 months (30 alive, 58 dead). The 5-year progression-free survival of all patients was 27% and the overall survival was 33%. Of patients with stage III disease debulked to lesions less than or equal to 1.5 cm before the initiation of chemotherapy (n = 34) the 5-year progression-free survival was 52%. Of 31 patients with a histologically documented complete response the median survival was 55+ months; 9 (29%) of them relapsed as opposed to 8 of 10 achieving microscopic residual disease at second look. Of 22 patients with stage IV disease, 20 died. This report confirms that patients who have undergone surgical removal of of bulk tumor and who achieve a complete remission have an improved survival outcome. PMID- 2107481 TI - Bone invasion by Walker 256 carcinoma, line A in young and adult rats: effects of etidronate. AB - Line A of Walker 256 carcinoma implanted in the muscle adjacent to the tibia of young (6 weeks) and adult (9 months) male rats invaded the bone. Osteolysis and reactive growth were greater in the bone of young animals than in adults. Ethane 1-hydroxy-1, 1-bisphosphonate prevented bone lysis and tumor invasion of the cortex both in young and adult animals. This model may be useful for studies of age-related differences in tumor infiltration into the bone and for investigating drug effects on this process. PMID- 2107482 TI - Effects of OK-432 (Picibanil) on estrogen receptor levels and tamoxifen treatment in 7,12-dimethylbenz[a]anthracene-induced rat mammary cancers. AB - The effects of OK-432 (Picibanil) on estrogen receptor (ER) levels and subsequent tamoxifen (TAM) treatment were examined in 189 female Sprague-Dawley rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary cancers. When OK-432 was administered (0.1 KE/kg i.p. once weekly) for 12 weeks to the rats after DMBA, the average ER level of the TAM-responsive tumors in the OK-432-treated group was significantly higher than that in the control group. The antitumor effect of TAM was significantly greater in the OK-432-treated group. When OK-432 was administered to rats with established DMBA tumors, the average ER levels did not change significantly after 2 or 4 weeks of treatment. ER levels in the control group (no treatment) fell significantly after 2 or 4 weeks. These results suggest that hormone dependence of DMBA-induced rat mammary cancers may be maintained or augmented by the administration of OK-432. PMID- 2107483 TI - Surgical miosis: have we been misled by a bunch of rabbits? PMID- 2107485 TI - Thresholds do not imply acceptability of low quality of care. PMID- 2107484 TI - AIDS under a competitive Medicaid program in a "second wave" state: Arizona's experience. AB - Arizona is a "second wave" state, ranking twenty-first among states in a number of reported AIDS cases. Interviews with 50 administrators and providers were used to determine how Arizona's Medicaid program, the Arizona Health Care Cost Containment System (AHCCCS), has responded to the AIDS epidemic. AHCCCS is a unique Medicaid program in which care is provided by health plans selected through competitive bidding on capitated rates. Policies that foster price competition among health plans may impede a timely and appropriate response to the AIDS epidemic, unless they take the character of this epidemic into account. PMID- 2107486 TI - Improving state-funded child psychiatric care: reducing protracted hospitalizations through changes in treatment planning. AB - In late 1986, Millcreek Psychiatric Center for Children changed several of its treatment practices in an attempt to decrease needlessly prolonged hospitalizations. The changes included initiating discharge planning shortly after admission, increasing contacts with community and judicial agencies, improving family therapy services, and educating the community about appropriate use of hospital treatments. The fraction of children hospitalized more than 180 days decreased significantly, as did the average length of stay. Mental health professionals should keep community agencies informed about the nature and limitations of inpatient treatment and about children's needs for adequate after care services. PMID- 2107487 TI - Procedure-specific costs and savings in a mandatory program for second opinion on surgery. AB - Initial examination of the surgery experience of participants in a large employer sponsored second opinion program revealed minimal savings in medical resource costs. But closer examination of relative savings for specific procedure categories showed that the greatest savings are for high-cost procedures: hysterectomy, prostatectomy, back surgery, and hip replacement. Furthermore, a nonconfirming second opinion does not dissuade patients from some procedures. Decisions about which procedures to include in a mandatory program should consider volume, costs, and effects of nonconfirmation, as well as the advantages of a mandatory second opinion for skeptical patients, or for patients for whom a controversial procedure has been recommended. PMID- 2107488 TI - Two approaches to measuring quality in medical case management programs. AB - In a study of the quality of care in a medical case management program, five physician experts, applying criteria to medical records, found the care provided appropriate in a majority of 40 cases (10 each of head injury, spinal cord injury, high-risk infants, and AIDS). Nurses interviewing parents of 30 high-risk infants found general satisfaction with case management. PMID- 2107489 TI - Contraband: the hidden risk. AB - In a 28-month retrospective study of contraband possession in an inpatient psychiatric setting, 54 incidents of contraband confiscation were identified. Incidents were analyzed according to day and shift of occurrence, nature of contraband, patient diagnoses and characteristics, and patient outcome of contraband possession. Study findings stress the importance of clearly stated contraband policies and procedures, especially in light of patient and staff rights and responsibilities. PMID- 2107490 TI - Isolation of human fos-related genes and their expression during monocyte macrophage differentiation. AB - cDNA clones of human fos-related genes fra-1 and fra-2 were isolated by screening human c-DNA libraries with human fos DNA as a probe. We obtained human fra-1 cDNA clones that can code for a protein of 271 amino acid residues with a calculated molecular weight of 29,413 and showed 90% similarity with rat fra-1 protein. A new fos-related gene, fra-2, has one long open reading frame of 326 amino acids, and can code for a protein with a calculated molecular weight of 35,193. Two regions, a leucine zipper domain and C-terminal region, are conserved in the fos gene family. The fra-2 gene also harbors these two regions. Transcription of the fos, fra-1 and fra-2 genes was induced by phorbol ester (TPA) stimulation of U937 human monocytic cells. On TPA stimulation, the transcriptions of fos, fra-1 and fra-2 were detectable after 30, 60 and 120 min and maximum after 60, 90 and 240 min, respectively. These findings suggest that expression of the fos gene family is regulated by an orderly mechanism. PMID- 2107491 TI - Abrogation of IL-3 dependent growth requires a functional v-src gene product: evidence for an autocrine growth cycle. AB - We have investigated the ability of the v-src oncogene to abrogate growth factor dependent growth in the interleukin-3 dependent myeloid progenitor cell line 32D c13. Growth factor independent clones were isolated following infection of 32D c13 cells with murine retroviruses containing the v-src oncogene. v-src was demonstrated to be directly responsible for growth factor independence in experiments utilizing temperature-sensitive v-src mutants. The v-src infected cells released a growth factor capable of stimulating the proliferation of normal 32D c13 cells. Analysis of the mRNA from v-src infected 32D c13 did not identify the putative autocrine growth factor as one of the currently identified murine or human hematopoietic growth factors. PMID- 2107492 TI - 2-Aminopurine abolishes EGF- and TPA-stimulated pp33 phosphorylation and c-fos induction without affecting the activation of protein kinase C. AB - Epidermal Growth Factor (EGF) and Tetradecanoyl Phorbol Acetate (TPA) initiate signalling cascades in C3H 10T1/2 fibroblasts by primarily activating distinct protein kinases, the EGF receptor tyrosine kinase and protein kinase C respectively; there is no signal crossover at the initiation of signalling. Nevertheless, we show here that both agents rapidly elicit common intracellular responses, including the phosphorylation of complexed and chromatin-associated forms of a 33 kDa phosphoprotein (pp33), that of a 15 kDa chromatin-associated phosphoprotein (pp15), as well as the transcriptional activation of a common subset of genes including the c-fos proto-oncogene. 2-aminopurine specifically abolishes complexed and chromatin-associated pp33 phosphorylation in response to EGF and TPA, as well as the induction of c-fos by both agents. The activation of protein kinase C and the levels of transcription factors that bind to the serum response element (SRE), TPA response element (TRE) or NFkB sites in stimulated cells are relatively unaffected by 2-aminopurine. This, to our knowledge, is the first demonstration that it is possible, by using 2-aminopurine which selectively blocks TPA-stimulated pp33 phosphorylation, to block c-fos induction in TPA treated cells although protein kinase C remains fully active. Further, we show here that although EGF- and TPA-stimulated induction of c-fos is abolished by 2 aminopurine, the appearance of TRE-binding activity in nuclear extracts of stimulated cells is unaffected, suggesting that EGF- and TPA-stimulated induction of TRE-binding activity utilises existing proteins and is not dependent on fresh c-FOS synthesis. These results imply that 2-aminopurine-sensitive complexed and chromatin-associated pp33 phosphorylation may be crucial to c-fos induction in response to EGF and TPA. PMID- 2107493 TI - Effects of specific fatty acids on cell transformation induced by an activated c H-ras oncogene. AB - An increase in dietary lipid has been associated with an increase in the development of certain forms of cancer, notably breast and colon cancer, both in experimental animal studies and in human epidemiology studies. The underlying mechanisms are not, however, known with certainty. In the present studies we have examined whether certain specific fatty acids (FA) might act by enhancing the role of an activated oncogene in a model cell culture system. We found that when the rat fibroblast cell line Rat 6 was transfected with an activated human c-H ras oncogene and the cells subsequently grown in medium supplemented with myristic acid, palmitic acid or stearic acid (20-80 microM) there was a marked enhancement of the number of transformed foci obtained. On the other hand arachidonic acid had a marked inhibitory effect in this transformation assay. However, this inhibitory effect can be partially reversed by indomethacin, an inhibitor of cyclo-oxygenase, at dose response manner. Control studies indicated that these results were not simply due to the effects of the FAs on growth of the Rat 6 cells or the process of transfection per se. Lipid analyses of cells grown in the presence of stearic acid indicated that the added FA was extensively incorporated into the major lipid classes of the cell and produced transient changes in lipid composition. This simple cell culture system may be useful for elucidating the mechanisms by which various dietary lipids and nutritional factors influence the carcinogenic process. PMID- 2107494 TI - Cross-talk in signal transduction: TPA-inducible factor jun/AP-1 activates cAMP responsive enhancer elements. AB - The product of the jun proto-oncogene has been identified as one form of the transcription factor AP-1. The p55fos protein associates with jun/AP-1 by means of a heterodimer which requires intact 'leucine zipper' domains of both proteins. The fos/jun heterodimer binds to and activates transcription from TPA-responsive promoter elements (TGACTCA), which represent one final target of the protein kinase C pathway. The other main signal transduction pathway, initiated by the activation of the adenylate cyclase, involves the transcription factor CREB. The promoter element recognized by CREB, a cyclic AMP responsive element (CRE), consist of a palyndromic sequence similar to a TRE (TGACGTCA). We show that jun efficiently trans-activates CRE sequences and that fos and jun efficiently bind and cooperate in activating CRE promoter elements. The similarity between TRE and CRE sequences may involve an interplay in transcriptional regulation and 'cross talk' between components of the two major signal transduction pathways. PMID- 2107495 TI - Laser therapy of the skin. A review of principles and applications. AB - Advances in laser technology now permit the physician to provide an effective form of treatment for a variety of cutaneous disorders for which no previous therapy existed. Additional refinements in both laser instruments and treatment techniques are certain to have a profound impact on the treatment of skin lesions. For that reason, a complete understanding of the basic properties of lasers and how they can be utilized in various clinical settings is the goal of this article. PMID- 2107496 TI - Rhinologic applications of laser surgery. AB - The use of lasers in the treatment of rhinologic conditions is described. Both intranasal and extranasal laser applications are discussed. The choice of an appropriate laser to suit the clinical situation is also examined. PMID- 2107497 TI - Use of the laser in the oral cavity. AB - Laser surgery is now commonly performed for lesions arising in the oral cavity. The laser provides certain advantages relating to the precision of tissue destruction and some hemostatic capabilities. However, it is the author's impression that it provides no special healing or cancer-killing advantages. It can be used for a wide variety of surgical procedures involving benign lesions. Its use for resection of oral cavity malignancies is restricted to verrucous cancers and smaller cancers. When the proper techniques are used to protect both the patient and the surgeon and other operating room personnel, it can be a safely performed surgical adjunct that has certain advantages over standard surgical approaches. PMID- 2107498 TI - Dermatologic laser surgery. AB - The first laser was constructed in 1959 and in only three decades lasers have achieved an important, well-established position in cutaneous surgery. The future is filled with rich opportunities for further investigation of the new laser systems and laser photobiology. PMID- 2107499 TI - Evidence for enhancement of IgG1 subclass expression in mice polyvaccinated with radiation-attenuated cercariae of Schistosoma mansoni and the role of this isotype in serum-transferred immunity. AB - Serum or immunoglobulin fractions of serum from CBA/Ca mice vaccinated three or four times with radiation-attenuated cercariae of Schistosoma mansoni have been investigated for their capacity to confer protection upon naive mice. The data confirm that around 35% protection can be transferred with polyvaccine mouse serum administered in 0.5-ml aliquots 1 h before challenge (intravenously) and 24 h post-challenge (intraperitoneally). We show in addition, however, that polyvaccine serum is also protective when injected into the skin site of challenge as a single 0.05-ml aliquot. In contrast, lymphocytes obtained from the donors of protective serum conferred only 13% protection upon recipient mice. The passive cutaneous anaphylaxis assay showed that IgG1 is incremented by polyvaccination, while passive transfer experiments revealed that of the different isotypes fractionated from whole protective serum, only IgG1 has the capacity to protect naive recipients against challenge. The resistance transferred by IgG1 represents more than 60% of that obtained with whole serum and can be achieved using either the intravenous/intraperitoneal or the subcutaneous administration regimen. Recipients of serum given via the subcutaneous route exhibit cutaneous inflammatory focal reactions which comprise 20% eosinophils and 80% mononuclear cells; these foci entrap challenge larvae. The importance of IgG1 subclass expression to the success of serum-transferred resistance is discussed. PMID- 2107500 TI - Immunization and challenge of mice with insect-derived metacyclic trypomastigotes of Trypanosoma cruzi. AB - Infection with Trypanosoma cruzi was established in the reduviid vector, Dipetalogaster maximus, by repeated feedings on mice with high parasitaemias, and metacyclic trypomastigotes (IMT) were collected in insect urine after blood meals. The infectivity of IMT in mice was assessed by placing varying numbers of organisms, ranging from 5 to 5000, on to the conjunctivae or oral mucosa of anaesthetized animals. Half of the mice exposed to as few as 20 IMT by either route became parasitized, and the minimum inoculum size that resulted in all mice becoming infected was 640 IMT by the ocular route and 1250 IMT in the mice given parasites by mouth. Mice were immunized by tail vein infusion of irradiated IMT. Animals in the immunized group and in two control groups were then challenged by deposition of IMT on to the oral mucosa. Two of five immunized mice and nine of 10 comparison animals developed acute T. cruzi infection after challenge. These results indicate that IMT produced in this system are highly infective and that inocula containing 500-1000 IMT applied to the conjunctivae or oral mucosa constitute a gentle contaminative challenge. Moreover, our findings suggest that sterile protection against a contaminative challenge may be inducible by immunization with IMT, but experiments involving larger numbers of animals must be performed to resolve this question. PMID- 2107501 TI - The effect of Blastocrithidia triatomae (Trypanosomatidae) on the midgut of the reduviid bug Triatoma infestans. AB - The pathogenic flagellate Blastocrithidia triatomae disrupts the digestion of Triatoma infestans; the midgut ultrastructure of bugs infected with the flagellate and of uninfected bugs is compared. Third or fourth instar larvae were dissected either unfed or 1 week after feeding. In all uninfected bugs extracellular membrane layers (e.m.l.) covered the apical microvillar border of the epithelial cells. Some midgut regions of bugs infected with B. triatomae appeared normal but often adjacent cells showed pathological effects. In affected cells the e.m.l. and the microvilli and finally the cells themselves were reduced or destroyed. Correlated with these observations of pathogenicity the method of attachment of parasites changed. When the e.m.l. were present only rarely were flagella found, but on extracellular membrane-free cells B. triatomae attached by flagellar enlargement to the microvillar border or, if this was reduced, to the apical host cell membrane. No hemidesmosome-like plaques were found at the attachment site. Although some flagella were inserted into the apical region of the cells no intracellular flagellates were observed. PMID- 2107502 TI - The effects of oxytetracycline on Theileria parva in vitro. AB - When bovine peripheral blood leucocytes were infected with Theileria parva sporozoites, immediate treatment with oxytetracycline (OTC) inhibited the development of sporozoites to mature schizonts. The extent of inhibition was dependent on drug concentration and duration of treatment. Concentrations of 5 micrograms/ml OTC, or higher, for 8 days completely inhibited the establishment of schizonts and their ability to transform host cells. A cytostatic effect on schizont-infected cell lines was found with three tetracyclines and was also demonstrated on uninfected lymphoblasts. The parasites were found to be sensitive to OTC during development to schizonts, but when mature and established within host cells, schizonts were not demonstrably affected. The infectivity of sporozoites and the binding of sporozoites to lymphocytes were not directly inhibited by OTC. The results may explain the action of tetracyclines when used prophylactically during immunization against East Coast fever, and also the reasons for the ineffectiveness of these drugs when used therapeutically during patent disease. PMID- 2107503 TI - Characterization of major surface and excretory-secretory immunogens of Trypanosoma cruzi trypomastigotes and identification of potential protective antigen. AB - The surface antigens of Trypanosoma cruzi trypomastigotes were identified by immunoprecipitation and were compared with metabolically labelled excretory secretory products (ES) released by the parasites in vitro. A series of major immunogenic components in the ES antigens were revealed (160 kDa, 130 kDa and 80 110 kDa). The trypomastigote surface also bears the 130 kDa band and the 80-110 kDa complex. Competition experiments demonstrated the common antigenic structure of the ES and the surface antigens. Two-dimensional analysis of ES antigens immunoprecipitated by human Chagasic serum revealed several spots in the 80-110 kDa region with a wide range of isoelectric points (PI between 5.4 and 6.7). This reflects a charge heterogeneity of these polypeptides. The trypomastigote 85 kDa polypeptide was also identified in the ES antigens by using a monoclonal antibody against this antigen. Two-dimensional analysis of the 85 kDa proteins shed from the surface of trypomastigotes and immunoprecipitated by the monoclonal antibody 155D3 showed 2 major spots: a major part of the 85 kDa polypeptide was found at pH 6.5-6.6, whereas a substantial amount of the antigen was found at pH 5.7. An additional component with molecular weight of approximately 58 kDa and isoelectric points of 6.5 and 6.6, was also visualized. Detection of the 85 kDa polypeptide circulating in serum from patients with acute and chronic Chagas' disease was achieved using an enzyme-linked immunosorbent assay. In addition, the data obtained showed that a polyclonal antibody to the 85 kDa polypeptide could be used to passively induce a partial protection of Fischer rats against acute lethal infection. Thus, the antigens recognized by polyclonal antibody appear to play a role in the development of protective immunity against T. cruzi. PMID- 2107504 TI - Schistosoma mansoni: morphology and ultrastructure of adult worms recovered from cyclosporin A-treated mice. AB - Cyclosporin A administered to Schistosoma mansoni-infected mice at around day 20 of infection reduces the worm burden by greater than 60%, as assessed by portal perfusion on days 28 and 86. Those worms recovered at perfusion have been examined by light and electron microscopy for drug-induced changes in morphology. Gross parasite damage was characterized by massive bolus formation and subsequent herniation of the gut. This event was attributed to the abnormal accumulation of crystalline structures in the lumen; the crystals were closely associated with lipid droplets, and were shown by X-ray micro-analysis to contain iron. Such crystals were seen only rarely in the intestines of control worms, but they too gave small iron peaks when examined by X-ray micro-analysis. In some drug-treated worms the caecal epithelium had ruptured, thereby releasing luminal contents throughout the worm body. In addition, herniations of the gut were seen protruding through the tegument causing surface deformation and disruption of tegumental and parenchymal tissues. The structural integrity of the worm was ultimately compromised allowing access to cytotoxic effector cells of the host. The combined effects of drug action and cellular cytotoxicity presumably account for the very significant levels of worm killing achieved by CsA treatment of the host. PMID- 2107505 TI - Toxicity of cyclosporin A (CsA) against developmental stages of Schistosoma mansoni in mice. AB - It has been shown elsewhere that the immunosuppressive drug cyclosporin A (CsA) exerts profound schistosomicidal activity when given to infected mice via a multiple administration regime. We show here that a single treatment regime also effects significant reductions in worm burden. Moreover, drug efficacy is maintained at CsA concentrations shown to be subimmunosuppressive in other systems. Subcutaneous treatment effected higher levels of schistosomicidal activity than intraperitoneal or oral treatment, irrespective of whether the drug was given prior to or during infection. Topical application of CsA to the skin site of cercarial penetration, prior to infection resulted in no reduction in worm burden. Systemic release of CsA from a slowly adsorbed, oil-based drug vehicle combination effected greater levels of killing than when CsA was dissolved in an aqueous drug vehicle. All developmental stages of Schistosoma mansoni were susceptible to killing by a single dose of CsA but, in the case of liver-stage worms, an increased concentration of drug and a longer period between treatment and portal perfusion were needed for killing to be measurable as a reduction in worm numbers. PMID- 2107506 TI - Schistosoma mansoni: analysis of the humoral and cellular basis of resistance in guinea-pigs vaccinated with radiation-attenuated cercariae. AB - This study addresses the humoral and cellular basis of specific acquired immunity in the guinea-pig irradiated vaccine model of schistosomiasis mansoni. Rodents vaccinated with 500 gamma-irradiated cercariae and then splenectomized 4.5 weeks later showed a 33% reduction in resistance to challenge as compared to vaccinated animals or vaccinated/sham splenectomized controls. Serum harvested from once vaccinated individuals conferred modest levels of resistance upon naive recipients in some experiments, but transfer was not achieved consistently. Serum from vaccinated and thrice boosted rodents (Vbbb) routinely transferred around 45% immunity, however, provided it was given in 4 ml aliquots on day 9 post challenge; Vbbb serum thus transferred 50% of donor immunity. Interestingly, multiple doses of this protective serum given on and either side of day 9 did not enhance the protection achieved with a single 4 ml aliquot. Neither peripheral lymph node cells nor splenocytes from the polyvaccinated serum donors were able to transfer resistance to recipient guinea-pigs and they failed to augment the protection achieved with Vbbb serum. Foot-pad testing revealed no correlation between delayed hypersensitivity responses and immunity to challenge in vaccinated guinea-pigs. Although polyvaccine guinea-pig serum successfully protected homologous recipients, it failed to protect mice when administered either at the time of challenge (the optimal schedule for transfer of polyvaccine mouse serum), or around day 9 (the optimal schedule for guinea-pigs). Similarly, guinea-pigs could not be protected with polyvaccine rat serum that conferred 75% resistance upon naive recipient rats. PMID- 2107507 TI - Schistosoma mansoni: evidence that site-dependent host responses determine when and where vaccine immunity is expressed in different rodent species. AB - Laboratory rodents vaccinated with highly irradiated cercariae of Schistosoma mansoni develop significant levels of specific acquired resistance yet effect challenge elimination in different organs. Mice and guinea-pigs are at opposite ends of the spectrum in this respect since, in our hands, vaccinated mice kill challenge parasites in the skin whereas vaccinated guinea-pigs kill challenge parasites predominantly in the liver. To determine whether this phenomenon is host-dependent (site) or parasite-dependent (stage), we have transferred worms harvested from mice or guinea-pigs into vaccinated recipient guinea-pigs. The results show that mouse-derived 5-day lung worms and 9-day liver worms that are essentially refractory to vaccine resistance in mice are indeed susceptible to vaccine resistance in guinea-pigs. Identical levels of susceptibility were recorded for lung-stage larvae introduced via the foot vein so as to experience lung and liver mechanisms, or via the mesenteric vein to bypass the lung, thereby confirming that vaccine resistance in guinea-pigs operates in the liver. Mouse worms and guinea-pig worms exhibited equivalent levels of susceptibility at all stages of development. Thirteen-day-old larvae from either donor species were on the border-line of vulnerability, while 20-day-old worms were totally refractory to vaccine immunity in guinea-pigs. These data show that vaccine immunity in different rodent species is a site-dependent, rather than a stage-dependent phenomenon. There is, however, an upper age limit of schistosome vulnerability which is common to worms harvested from different donor species. PMID- 2107508 TI - Schistosoma mansoni: stage-dependent damage after in vivo treatment with praziquantel. AB - The in vivo effects of a single, subcurative dose (200 mg/kg body wt of mouse) of praziquantel on the structure of the tegument and subtegumental tissues of juvenile (21-, 26- and 30-day-old) and adult Schistosoma mansoni are described. In juvenile worms praziquantel caused only moderate damage to both the tegument and subtegumental tissues although the degree of drug-induced damage was related to both the sex of the worms and to the developmental status of each individual worm. In general, male worms exhibited more extensive and longer lasting surface damage than females. However, the level and extent of the changes increased as the worms became more developmentally advanced with adult worms showing extensive damage to the tegument and vacuolization and disruption of the subtegumental tissues. The possible correlation between the stage-dependent changes in susceptibility to praziquantel and age-related changes, particularly in the phospholipid composition of the outer tegumental membrane is discussed. PMID- 2107509 TI - Polyclonal activation of B lymphocytes during experimental infection with Schistosoma mansoni. AB - A significant polyclonal activation of B lymphocytes was observed during experimental infection of C57BL/10J mice with Schistosoma mansoni. The isotypic pattern of this expansion, assessed by the Protein-A plaque-forming cell method, was compared with and found to differ from those occurring after infection by Trypanosoma cruzi or injection of bacterial LPS. In the infection of S. mansoni an early expansion of most immunoglobulin isotypes occurs together with a late, sustained expansion of IgG1-secreting cells. High levels of polyclonal B cell activation were observed after adoptive transfer of spleen cells from infected mice to isogenic recipients pre-treated with hydroxyurea. PMID- 2107510 TI - [Current role of the laboratory in the demonstration and follow up of monoclonal immunoglobulinopathy]. AB - The interest of new methodologies (electrophoresis in agarose, immunofixation, quantitation of Ig G, Ig A, Ig M and light chains kappa/lambda ratio) to diagnose monoclonal gammopathies, was discussed. A strategy using a combination of these new procedures was exposed. Serum level of beta-2 microglobulin can be used to monitor response to therapy in myeloma when the quantitation of monoclonal Ig is not possible. PMID- 2107511 TI - [In vitro bactericidal rate of amikacin at concentrations realizable in vivo]. AB - The bactericidal rate of amikacin in vitro was established by varying bacterial cell density (10(5) and 10(6) CFU/ml) and physiological state (lag phase and onset of exponential growth) at the moment the antibiotic was introduced. This was done with nine strains belonging to five different species. Antibiotic concentrations were those obtained in vivo at the valley (4 micrograms/ml) and the peak (20 micrograms/ml) with a dosage of 5 mg/kg. The concentration of 40 micrograms/ml is the peak value in the context of hypothesis of a short-term treatment with reinforced dosage (10 mg/kg). The bactericidal effect of amikacin, generally rapid, increased with increasing drug concentration. A bactericidal effect of 99.9% or even 99.99% was obtained in one hour or less at the concentration of 40 micrograms/ml. Above all, this concentration prevented regrowth or rebound, observed at lower concentrations. This results from a rapid but above all powerful bactericidal effect, practically total and constitutes a bacteriological argument in favor of an increase in dosage combined with a reduction in the length of treatment. PMID- 2107512 TI - [Evaluation of the bactericidal effect of the membrane attack complex of serum complement]. AB - The bactericidal activity of serum complement and particularly of the membrane attack complex (MAC-C5b-C9) was studied on E. coli C600 with a simple functional test. The test evaluates the in vitro kinetics of the bactericidal effect and the subsequent counting of surviving germs. Homozygous deficiency of a particular membrane attack complex protein was easily detected from a total loss of bactericidal activity. These results were confirmed on Neisseriae meningitidis A and C, but in this case a more complex protocol was required. Deficits of proteins of the membrane attack complex sequence of complement are often found in sera of patients suffering from recurrent Neisseriae infections. This simple test, adapted to family studies, appears, thus, as a valuable basis for a detection of relatives at risk. PMID- 2107513 TI - Endothelium-derived relaxing factor: presence in pulmonary and systemic arteries of the newborn guinea pig. AB - Endothelium-derived relaxing factor (EDRF), believed to be nitric oxide or a compound that releases nitric oxide, is a potent vasodilator produced by some arteries in response to acetylcholine (ACh) and bradykinin (BK). ACh and BK are potent dilators of perinatal pulmonary and systemic arteries. The objectives of this study were to determine if EDRF is present in newborn vessels and if EDRF mediates the vasodilator actions of ACh and BK. Arterial rings from newborn guinea pigs, 1 to 3 d old, were obtained from a branch of the main pulmonary artery and the descending aorta for isometric force bioassays. At their optimal resting tension, the rings were preconstricted with phenylephrine 10(-5) M in Krebs-Henseleit solution before adding incremental doses of ACh or BK. If the endothelium was intact, ACh (10(-5) M) relaxed pulmonary arteries and aortas (64 +/- 7%, 72 +/- 9% relaxation, respectively, mean +/- SE). ACh-induced relaxation (ACh 10(-5) M) in the pulmonary artery and aorta, respectively, was significantly (p less than 0.05) attenuated by 1) endothelial removal (11 +/- 9%, 28 +/- 10%) by rubbing the ring lumen; 2) methylene blue, 10(-6) M, (6 +/- 8%, 7 +/- 3%) that inhibits EDRF-associated cGMP production in smooth muscle; and 3) methemoglobin, 10(-5) M, (13 +/- 9%, 17 +/- 7%) that binds EDRF. The results for BK were similar to ACh for the pulmonary artery but BK did not relax the aorta. Indomethacin diminished relaxation of the pulmonary artery and aorta to the submaximal dose (10(-5) M) of ACh but indomethacin did not effect the relaxation to ACh 10(-4) M or BK. We conclude that EDRF is produced in the guinea pig pulmonary artery and descending aorta at birth and that EDRF is a mediator of the vasodilator actions of ACh and BK. Vasodilation by ACh may also involve activation of the cyclooxygenase pathway. PMID- 2107514 TI - Successful treatment of pericarditis associated with Mycoplasma pneumoniae infection. PMID- 2107515 TI - Abnormal maxillary sinus radiographs in children: do they represent bacterial infection? AB - Thirty-three children with chronic tonsillitis and/or adenoid enlargement and without previous diagnosis of sinusitis were studied regarding the bacterial flora of their maxillary sinuses. Puncture of maxillary sinus was performed at surgery (adenoidectomy and/or tonsillectomy) and aspirates were cultured. Streptococcus pneumoniae was isolated from 8 of 12 (66.7%) patients whose x-rays showed completely opacified maxillary sinus. Streptococcus viridans, Streptococcus faecalis, and Staphylococcus epidermidis were recovered from 6 (28.6%) of the 21 patients with normal maxillary sinus radiographs. Bacterial titers were greater than 10(4) colonies/mL in all but one of the positive cultures. No anaerobic bacteria were isolated. History of bronchial asthma, presence of nasal purulent secretion, elevated blood eosinophils, and elevated serum IgE were found more frequently in children with complete opacification of maxillary sinus. Serum levels of IgG2 were low in 29% of the children, but no correlation was found between low IgG2 levels and positive cultures from maxillary sinus aspirates. We concluded that children with complete radiologic opacification of maxillary sinus had bacterial infection in almost 70% of the cases with symptoms that did not prompt their physicians to consider the diagnosis of sinusitis. PMID- 2107516 TI - Comparative immune responses to Haemophilus influenzae type b polysaccharide and a polysaccharide-protein conjugate vaccine. PMID- 2107517 TI - Immunogenicity of a new Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB). AB - Haemophilus influenzae type b is responsible for an estimated 15,000 to 20,000 cases of meningitis per year in the United States, mainly in children 2 months to 5 years old. The mortality rate from meningitis due to H influenzae type b infections ranges from 5% to 10%. Despite antibiotic treatment, up to 35% of survivors have permanent neurologic sequelae. In addition to meningitis, H. influenzae type b is responsible for other invasive infections, including epiglottitis, septicemia, cellulitis, septic arthritis, osteomyelitis, pneumonia, pericarditis, and otitis media; approximately 30,000 cases H influenzae diseases occur annually in the United States. The diseases peak in incidence between 6 and 12 months of age, with almost one half of the cases occurring before 1 year of age. About 75% of disease caused by H influenzae type b occurs in children younger than 24 months old. The incidence of disease is higher in children of certain groups, including blacks, Hispanics, Eskimos and Native Americans, young children attending day-care facilities, patients with asplenia or antibody deficiency syndromes, and children of lower socioeconomic status. There is considerable evidence that antibody to the capsular polysaccharide (polyribosylribitol-phosphate [PRP] of H influenzae type b is protective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107518 TI - Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB): clinical evaluation. AB - Although systemic infections caused by Haemophilus influenzae type b occur worldwide, detailed epidemiologic data are available in but a few countries. The public health impact of morbidity, mortality, and serious sequelae from disease caused by H influenzae type b has stimulated the search for control strategies. In the United States now, active immunoprophylaxis is largely favored over treatment of prophylaxis with antibiotics. This preference stems from three major observations: that high mortality and morbidity persist despite the availability of potent antimicrobial agents, that antibiotic-resistant strains of H influenzae type b have emerged, and that implementation of antimicrobial prophylaxis on a large scale has been unsatisfactory. Moreover, universal vaccination has been projected as offering a higher economic benefit than other control strategies. A matter of more proximate importance, however, is the search for H influenzae type b vaccines that will confer protection to all age groups, including infants younger than 18 months of age and subpopulations specifically at risk for invasive disease caused by H influenzae type b. Haemophilus b conjugate vaccine (meningococcal protein conjugate), PedvaxHIB (PRP-OMPC), is a conjugate H influenzae type b vaccine developed at Merck Sharp & Dohme Research Laboratories that now is undergoing extensive clinical evaluation to assess its prospects for disease control when first administered in early infancy. This is an interim report of results obtained in studies conducted in diverse locations throughout the United States. PMID- 2107519 TI - Safety, tolerability, and immunogenicity of concurrent administration of Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) with either measles-mumps-rubella vaccine or diphtheria-tetanus-pertussis and oral poliovirus vaccines in 14- to 23-month-old infants. AB - In 1985, the first capsular polysaccharide (polyribosylribitol-phosphate [PRP]) vaccine for Haemophilus influenzae type b was licensed and recommended for routine use in children between 24 and 60 months of age. In the United States, approximately 75% to 90% of invasive disease due to H influenzae type b occurs in infants younger than 24 months, a population for whom H influenzae type b polysaccharide vaccine is inadequately immunogenic and protective. In an effort to enhance the immunogenicity of H influenzae type b polysaccharide vaccine for children in the most susceptible age groups, conjugate vaccines have been developed in which the capsular PRP of H influenzae type b has been bound to a variety of carrier proteins, thereby conferring the vaccines with thymic dependent attributes. One such conjugate vaccine, in which the carrier protein is diphtheria toxoid (PRP-D), was licensed in 1987 and has been recommended since 1988 for routine use in children 18 months of age and older. A second conjugate vaccine, in which an oligosaccharide derivative of H influenzae type b capsular PRP is coupled to CRM, a nontoxic mutant diphtheria toxin (oligo-CRM), was licensed in 1988 and is a sanctioned alternative to PRP-D. Another investigational conjugate vaccine, in which the polysaccharide is linked to the outer membrane protein of Neisseria meningitidis group B (PRP-OMPC), has been demonstrated to be both safe and immunogenic when administered in a two-dose schedule to 2- to 6-month-old infants. However, anti-PRP antibody levels decline significantly during the ensuing 10 to 15 months; they rise significantly in response to booster doses of either PRP or PRP-OMPC administered 10 to 15 months after the initial priming doses of PRP-OMPC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107520 TI - Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate): immunogenicity and safety at various doses. AB - The Haemophilus influenzae vaccine consisting of purified type b capsular polysaccharide (polyribosylribitol-phosphate [PRP]) was shown in Finland to be protective, with 90% efficacy in children older than 18 to 23 months of age. However, a wide range of estimates of vaccine efficacy has been reported in the United States after its licensure in 1985. These estimates range from -55% to +89%. In addition, the PRP vaccine was not effective in children younger than 18 months of age, in whom 70% to 80% of meningitis cases occur. A further development was the introduction of H influenzae type b polysaccharide-protein conjugate vaccines such as the PRP-D. These conjugate vaccines were found to be more immunogenic than PRP vaccine in children of all ages. Two doses of PRP-D in infants 7 months of age and older induced antibody levels equal to or greater than levels in infants 24 months of age who received the PRP vaccine alone. Recently, Eskola et al reported that repeat vaccinations with PRP-D at 3, 4, 6, and 14 months of age was 83% protective (95% confidence interval, 26% to 96%). Yet PRP-D vaccine elicits only low serum antibody levels in infants younger than 7 months of age. Because of the discrepancy in efficacy results for the PRP vaccine in the United States and Finland and the lack of data about the protective efficacy of PRP-D vaccine in infants in the United States, the PRP-D vaccine is currently recommended only for children 18 months of age or older.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107521 TI - Opsonophagocidal activity in sera from infants and children immunized with Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate). AB - Immunization with Haemophilus influenzae type b capsular polysaccharide (polyribosylribitol-phosphate [PRP]) has resulted in limited and variable antibody radioimmunoassay in infants younger than 2 years of age. Although an H influenzae type B vaccine has been in use for several years, it is not used now for the age group at greatest risk for disease. In an effort to enhance immunogenicity, PRP has been coupled to various carrier proteins and to an outer membrane protein complex (OMPC) from Neisseria meningitidis group B. The latter approach has yielded a vaccine that elicits a good antibody response after a single 15-micrograms dose of vaccine in infants as young as 2 months of age, as measured by radioimmunoassay and immune bacteriolysis. In this report we describe the results of a pilot study using this H influenzae type B conjugate vaccine, PedvaxHIB, in children from 2 months to 4 years of age. Three different vaccine lots were examined for consistency of response. Sera were measured for antibody levels by radioimmunoassay and for functional activity using an opsonophagocytic assay using human adult neutrophils. These assays correlated well and demonstrated the excellent immune response and biologic activity of sera from infants vaccinated with this unique H influenzae type B conjugate vaccine. PMID- 2107522 TI - Disease caused by Haemophilus influenzae type b in the immediate period after homologous immunization: immunologic investigation. AB - Several Haemophilus influenzae type b vaccines have been licensed and recommended for administration to children in the United States. These vaccines have consisted of purified polyribosylribitol-phosphate (PRP), the capsular polysaccharide of H influenzae type b, alone or covalently bound to one of several carrier proteins. Two of these saccharide-protein conjugate vaccines are now licensed, a polysaccharide-diphtheria toxoid conjugate (PRP-D) and an oligosaccharide-mutant diphtheria toxin conjugate (HbOC). Two others, a polysaccharide-Neisseria meningitidis outer membrane protein conjugate (PRP-OMPC) and a polysaccharide-tetanus toxoid conjugate (PRP-T), are currently in clinical trials. One concern with the use of PRP vaccine was the suggestion that the incidence of invasive disease caused by H influenzae type b in the immediate period after immunization might be increased; this idea was supported by evidence from several sources. In a case-control study of the efficacy of PRP vaccine, Black et al found that 4 children were hospitalized for invasive disease within 1 week of immunization, a rate of invasive disease 6.4 times greater (95% confidence interval [CI], 2.1 to 19.2) than the background rate in unvaccinated children. In Minnesota, the relative risk for invasive disease in the first week after immunization was 6.2 (95% CI, 0.6 to 45.9), and the results of a study conducted by the Centers for Disease Control in six areas of the United States revealed a 1.8-fold (95% CI, 0.3 to 10.2) increase in the occurrence of invasive disease caused by H influenzae type b in the first week after immunization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107523 TI - Fever response induced by intravenous and intracerebroventricular injection of pyrogen in thyroidectomised and protein-calorie malnourished rabbits. AB - The development of a fever in response to intravenous (IV, 1.5 micrograms/kg body mass) and intracerebroventricular (ICV, 1.5 micrograms/animal) injections of Escherichia coli lipopolysaccharide (LPS) was studied in control, thyroidectomised and protein-calorie malnourished rabbits (New Zealand Whites, n = 55). ICV injection of LPS in control rabbits produced a fever response, the characteristics of which differed from those obtained after IV pyrogen injection. Thyroid deficiency caused an attenuated fever response, irrespective of whether LPS had been administered by IV or ICV injection. Protein-calorie malnourished rabbits showed a smaller fever response after IV or ICV pyrogen injections. Malnourished rabbits, refed over a period of 15 days, showed a typical biphasic fever response, but with lower magnitude than controls. The results of these experiments suggest that ICV injection of LPS is not an appropriate model for the study of fever mechanisms in disease states, and that the attenuated fever response observed in protein-calorie malnourished rabbits may be related, at least in part, to a decreased ability to produce the endogenous pyrogen interleukin-1. PMID- 2107524 TI - Immunoglobulin heavy chain gene organization and complexity in the skate, Raja erinacea. AB - Immunoglobulin heavy chain genes from Raja erinacea have been isolated by cross hybridization with probes derived from the immunoglobulin genes of Heterodontus francisci (horned shark), a representative of a different elasmobranch order. Heavy chain variable (VH), diversity (DH) and joining (JH) segments are linked closely to constant region (CH) exons, as has been described in another elasmobranch. The nucleotide sequence homology of VH gene segments within Raja and between different elasmobranch species is high, suggesting that members of this phylogenetic subclass may share one VH family. The organization of immunoglobulin genes segments is diverse; both VD-J and VD-DJ joined genes have been detected in the genome of non-lymphoid cells. JH segment sequence diversity is high, in contrast to that seen in a related elasmobranch. These data suggest that the clustered V-D-J-C form of immunoglobulin heavy chain organization, including germline joined components, may occur in all subclasses of elasmobranchs. While variation in VH gene structure is limited, gene organization appears to be diverse. PMID- 2107526 TI - Nck, a melanoma cDNA encoding a cytoplasmic protein consisting of the src homology units SH2 and SH3. PMID- 2107525 TI - Identification of a second inducible DNA-protein interaction in the kappa immunoglobulin enhancer. AB - Control of kappa immunoglobulin light-chain gene expression requires the interaction of tissue specific and developmentally regulated DNA-binding proteins with the kappa gene enhancer. Deletion of enhancer sequences upstream from the NF kB binding site has been shown to impair enhancer function, implying additional proteins may interact with these sequences. In surveying this region for sites of protein binding, a novel DNA-protein interaction, designated kBF-A, was detected. The binding activity of this factor appears to be specific to activated pre-B cells and correlates with high level induction of kappa transcription in these cells. PMID- 2107527 TI - Improved yields of long PCR products using gene 32 protein. PMID- 2107528 TI - Variant tissue-type plasminogen activator (PLAT) cDNA obtained from human endothelial cells. PMID- 2107529 TI - Structure, organization and evolution of the L1 equivalent ribosomal protein gene of the archaebacterium Methanococcus vannielii. AB - The gene for ribosomal protein MvaL1 from the arachaebacterium Methanococcus vannielii was cloned and characterized. It is clustered together with the genes for MvaL10 and MvaL12, thus is organized in the same order as in E.coli and other archaebacteria. Unexpectedly, analysis of the sequence in front of the MvaL1 gene revealed an ORF of unknown identity, whereas in E.coli, Halobacterium and Sulfolobus solfataricus the gene for the L11 equivalent protein is located in this position. Northern blot analysis revealed a single tricistronic transcript encoding proteins MvaL1, MvaL10 and MvaL12. The 5'-end of the MvaL1-L10-L12 transcript contains a region that has a sequence and structure almost identical to a region on the 23S rRNA which is the putative binding domain for MvaL1, and is highly similar to the E.coli L11-L1 mRNA leader sequence that has been implicated in autogenous translational regulation. Amino acid sequence comparison revealed that MvaL1 shares 30.5% identity with ribosomal protein L1 from E.coli and 41.5% and 33.3% identity with the L1-equivalent proteins from the archaebacteria H.cutirubrum and S.solfataricus respectively. PMID- 2107530 TI - Heat-inducible translational coupling in Bacillus subtilis. AB - Bacillus subtilis plasmid pGR71 is a promoter-probe shuttle vector derived from pUB110. The expression of the cat gene on pGR71 in B. subtilis requires the insertion of a Bacillus promoter and a ribosomal binding site (RBS) into the HindIII cloning site immediately upstream from the cat gene. A recombinant plasmid of pGR71, named pGR71-369, was obtained by a spontaneous deletion of a fragment containing most of the inserted HindIII fragment and the replication origin necessary for multiplication in Escherichia coli. The expression of the cat gene in B. subtilis cells carrying this plasmid was inducible by heat. Nucleotide sequence analysis of the upstream region of the cat gene, deletion analysis, and dot blot hybridization analysis of mRNA in various conditions revealed that the cat gene was expressed by heat-inducible translational coupling and that the regulatory region of heat inducibility was present in the upstream region of the cat gene. PMID- 2107531 TI - A mutation in the Zn-finger of the GAL4 homolog LAC9 results in glucose repression of its target genes. AB - The transcriptional activator LAC9, a GAL4 homolog of Kluyveromyces lactis which mediates lactose and galactose-dependent activation of genes involved in the utilization of these sugars can also confer glucose repression to those genes. Here we report on the isolation and characterization of LAC9-2, an allele which encodes a glucose-sensitive activator in contrast to the one previously cloned. A single amino acid exchange of leu-104 to tryptophan is responsible for the glucose-insensitive phenotype. The mutation is located within the Zn-finger-like DNA binding domain which is highly conserved between LAC9 and GAL4. Glucose repression is also eliminated by duplication of the LAC9-2 allele. The data indicate that LAC9 is a limiting factor for beta-galactosidase gene expression under all growth conditions and that glucose reduces the activity of the activator. PMID- 2107532 TI - Internal eliminated sequences are removed prior to chromosome fragmentation during development in Euplotes crassus. AB - The hypotrichous ciliated protozoa undergo a massive genome rearrangement process after their sexual cycle. One frequent type of rearrangement is the removal of DNA sequences (internal eliminated sequences; IESs) from internal regions of DNA molecules. In this study, we characterized the removal of IESs in Euplotes crassus. Southern hybridization analyses combined with cytological observations indicated that IES removal is an early event in macronuclear development, occurring during the polytene chromosome stage and prior to the chromosome fragmentation process. The results are consistent with IES removal occurring via an intramolecular DNA breakage and rejoining process. PMID- 2107533 TI - The roles of indoleglycerol phosphate and the TrpI protein in the expression of trpBA from Pseudomonas aeruginosa. AB - The TrpI protein belongs to the LysR-family of procaryotic regulatory proteins. Members of this family share a characteristic similarity of their N-terminal amino acid sequences, and many of them are activators of divergently transcribed genes or operons. In Pseudomonas aeruginosa, the genes for tryptophan synthase, trpBA, are regulated by indoleglycerol phosphate (InGP) and TrpI. We demonstrate here that in the absence of InGP, the binding site of TrpI is located in the -52 to -77 region of the trpBA promoter; in the presence of InGP, the binding region is extended to the -32 region. In addition, two major, slow moving protein-DNA complexes are seen in gel retardation assays: the faster moving complex is formed in the absence of InGP and the amount of the slower moving complex is greatly enhanced in the presence of InGP. These results suggest that the binding of a second TrpI protein molecule, promoted by InGP, plays a crucial role in activating the expression of the trpBA gene pair. PMID- 2107534 TI - Nursing implications in the administration of ifosfamide and mesna. PMID- 2107535 TI - A nationwide survey of prescribing patterns for thrombolytic drugs in acute myocardial infarction. AB - In November 1988, 164 hospitals enrolled in the Drug Surveillance Network participated in a nationwide survey of prescribing patterns for thrombolytic drugs for patients with an acute myocardial infarction. The results indicated that alteplase has made dramatic inroads, being used exclusively in 14.6% of the hospitals; in 64% of the hospitals both alteplase and streptokinase were on the formulary. Overall, however, only 17% of patients admitted with an acute myocardial infarction were treated with a thrombolytic, and use of these agents varied markedly across institutions. One of the reasons for this low figure may be the current maximum allowable time from onset of symptoms to administration of a thrombolytic. This time limit was less than 6 hours in the majority of hospitals in spite of recent evidence suggesting that these drugs may be effective up to 24 hours after onset of symptoms. The low and variable use of the agents for acute myocardial infarction suggests the need to identify patient- and physician-related obstacles so that overall attitudes and professional practice can be modified to reverse this trend. Given large number of institutions reporting the presence of formal, prospective, pharmacy-initiated monitoring programs, we suggest that clinical pharmacists will play a major role in implementing the necessary changes. PMID- 2107536 TI - Chronic granulomatous disease of childhood: clinical, pathological, biochemical, molecular, and genetic aspects of the disease. AB - The pathobiology of chronic granulomatous disease (CGD) of childhood, a heterogeneous phenotypic disorder characterized by chronic and recurrent infection, has become more completely understood over the past three decades. Blood neutrophils, monocytes, and eosinophils lack a respiratory burst required for effective killing of catalase positive bacteria by reduced by-products of oxygen. The disease is transmitted in at least two genetic forms: X-linked and autosomal recessive. In the X-linked form, a gene coding for a beta subunit protein required for cytochrome b presence on the plasma membrane of phagocytic cells is not expressed. The protein appears to be a constituent of the cytochrome b complex that requires an additional alpha subunit for complete expression. Cytochrome b is likely a component of leukocyte oxidase, which catalyzes the respiratory burst. The autosomal recessive form of the disorder appears to be controlled by a set of genes coding for soluble cofactors essential for oxidase expression. One or more of these cofactors have recently been shown to be deficient in several patients with autosomal recessive CGD. Optional therapy for CGD patients is presently not available. Long-term use of antibiotics may be helpful. The cloned product interferon gamma has been reported to improve superoxide generation, bactericidal activity, and immunoreactive cytochrome b in some CGD neutrophils and monocytes, both in vitro and in vivo. Currently a prospective clinical evaluation of the efficacy of interferon gamma is in progress. Molecular studies of expression and function of the X-CGD gene in phagocytic cells are in progress as well. PMID- 2107537 TI - Umbilical cord haematoma as a complication of intrauterine intravascular blood transfusion. AB - Between October 1985 and February 1989, 49 ultrasound-guided intravascular fetal blood transfusions were performed in 16 patients (14 with rhesus (Rh) isoimmunization, 2 with non-immunologic hydrops fetalis (NIHF)). As an intra operative complication, perivascular haematoma of the cord occurred in three patients (7 per cent). In two cases, fetal bradycardia necessitated delivery by Caesarean section at 30 and 32 weeks' gestation, respectively. In the third case, fetal bradycardia developed during transfusion, at 31 weeks' gestation, but normalized within 3 min. The baby was delivered as planned at 36 weeks of gestation, after another transfusion at 34 weeks. Dislodgement of the needle tip into perivascular tissue, caused by sudden fetal or maternal movements, is the reason for this complication. The haematoma develops as a result of delayed recognition and continuous transfusion into Wharton's jelly. Cord haematoma may be diagnosed in time by continuous ultrasound imaging, as illustrated in case 3. To minimize the risk of needle dislodgement during transfusion, sedation of the mother and complete immobilization of the fetus by injecting a short-acting muscle relaxant into the umbilical vessel are recommended. PMID- 2107538 TI - [Cystic lymphangioma of the omentum]. PMID- 2107539 TI - Is food allergy a cause of acute pancreatitis? AB - We reported two cases of acute recurrent pancreatitis lasting for 8 and 10 years, respectively, and characterized by acute abdominal pain associated with an increased serum level of pancreatic enzymes and in one case transient enlargement of the pancreas on sonography and CT scan. Exocrine and endocrine pancreatic function remained normal. Pain attacks were associated with headache or typical migraine, myalgia, pruritus, and diarrhea. In one case only, the IgE serum level was increased. In both cases, the symptoms were reproduced in the 2 h following the consumption of some particular food and cured for years by the suppression of this food and the use of cromoglycate, but recurred 1 month to 3 years after this treatment was stopped, to be again healed by the same treatment. We suggest that these cases are due to food allergy and that food allergy could be a rare cause of acute recurrent pancreatitis. Responsible foods were beef (twice), milk, potato, fish, and eggs, which is in agreement with the frequency of food allergens in southwestern Europe. PMID- 2107540 TI - Resistance to juvenile hormone and an insect growth regulator in Drosophila is associated with an altered cytosolic juvenile hormone-binding protein. AB - The Met mutant of Drosophila melanogaster is highly resistant to juvenile hormone III (JH III) or its chemical analog, methoprene, an insect growth regulator. Five major mechanisms of insecticide resistance were examined in Met and susceptible Met+ flies. These two strains showed only minor differences when penetration, excretion, tissue sequestration, or metabolism of [3H]JH III was measured. In contrast, when we examined JH III binding by a cytosolic binding protein from a JH target tissue, Met strains had a 10-fold lower binding affinity than did Met+ strains. Studies using deficiency-bearing chromosomes provide strong evidence that the Met locus controls the binding protein characteristics and may encode the protein. These studies indicate that resistance in Met flies results from reduced binding affinity of a cytosolic binding protein for JH III. PMID- 2107541 TI - GAL4 transcription factor is not a "zinc finger" but forms a Zn(II)2Cys6 binuclear cluster. AB - The DNA-binding domain of the transcription factor GAL4, consisting of the 62 N terminal residues and denoted GAL4(62*), contains a Cys-Xaa2-Cys-Xaa6-Cys-Xaa6 Cys-Xaa2-Cys-Xaa6+ ++-Cys motif, which has been shown previously to bind two Zn(II) or Cd(II) ions. Binding of Zn(II) or Cd(II) is essential for the recognition by GAL4 of the specific palindromic DNA sequence to which it binds upstream of genes for galactose-metabolizing enzymes, the UASG sequence. On the basis of the 113Cd NMR chemical shifts of the two bound 113Cd(II) ions, we propose a binuclear cluster model for this Zn(II)-binding subdomain. 1H-113Cd heteronuclear multiple-quantum NMR spectroscopy and phase-sensitive double quantum filtered 1H correlation spectroscopy of the 112Cd(II)- and 113Cd(II) substituted GAL4(62*) derivatives provide direct evidence that the two bound 113Cd(II) ions are coordinated only by the six cysteine residues, two of which form bridging ligands between the two 113Cd(II) ions. The latter can be identified from the pattern of 1H-113Cd J coupling. Thus a binuclear metal ion cluster rather than a "zinc finger" is formed by the six cysteine residues of the GAL4 DNA-binding domain. This model can be directly applied to eight other fungal transcription factors which have been shown to contain similarly spaced Cys6 clusters. 1H NMR spectra of apo-GAL4(62*) suggest conformational fluctuation of the metal-binding subdomain upon removal of Zn(II) or Cd(II). Both Cd(II)2- and Zn(II)2-containing species of GAL4 can be formed, and the similar 1H NMR spectra suggest similar conformations. PMID- 2107542 TI - Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis. AB - Hemophilia A results from mutations in the gene coding for coagulation factor VIII. We used denaturing gradient gel electrophoresis to screen for mutations in the region of the factor VIII gene coding for the first acidic domain. Amplification primers were designed employing the MELTMAP computer program to optimize the ability to detect mutations. Screening of amplified DNA from 228 unselected hemophilia A patients revealed two mutations and one polymorphism. Rescreening the same population by making heteroduplexes between amplified patient and control samples prior to electrophoresis revealed one additional mutation. The mutations include two missense and one 4-base-pair deletion, and each mutation was found in patients with severe hemophilia. The polymorphism, located adjacent to the adenine branch site in intron 7, is useful for genetic prediction in some cases where the Bcl I and Xba I polymorphisms are uninformative. These results suggest that DNA amplification and denaturing gradient gel electrophoresis should be an excellent strategy for identifying mutations and polymorphisms in defined regions of the factor VIII gene and other large genes. PMID- 2107543 TI - The trithorax gene, a trans-acting regulator of the bithorax complex in Drosophila, encodes a protein with zinc-binding domains. AB - The trithorax (trx) gene functions in segment determination in Drosophila through interaction with genes of the bithorax complex and Antennapedia complex. Genetic evidence suggests that trx may be considered a positive regulator of homeotic genes. Sequencing of cDNAs corresponding to the entire trx transcription unit revealed the existence of an unusually long open reading frame encoding 3759 amino acids. The main features of the predicted trx protein are several cysteine rich regions which can be folded into zinc finger-like domains. Cysteine-rich portions expressed from trx cDNAs in Escherichia coli are capable of zinc binding in vitro, suggesting a possible function for the trx product as a metal-dependent DNA-binding protein. Analysis of trx mutant embryos with antibody to the Ultrabithorax (Ubx) gene product showed decreased staining in parasegment 6 of the ventral nerve cord of late embryos. However, expression of Ubx was not affected in embryos carrying the lethal mutation trxE3, in which one of the putative zinc finger-like domains of the trx protein is deleted. This differential effect of the E3 mutation suggests that trx exhibits other function(s) besides those involved in the regulation of Ubx expression in the ventral nerve cord of the embryo. PMID- 2107544 TI - K(+)-evoked Muller cell depolarization generates b-wave of electroretinogram in toad retina. AB - We tested the hypothesis that a light-evoked increase in [K+]o produces a depolarization of the Muller cell membrane, which in turn generates the electroretinogram b-wave current. Using Bufo marinus isolated retinas and K(+) selective microelectrodes, we recorded two distinct light-evoked increases in extracellular K+ concentration: one in the inner plexiform layer and the other near the outer plexiform layer; the "distal" K+ increase was found over only 10 microns depth and had a maximum amplitude of 0.3 mM. We also recorded the electroretinogram and the light-evoked responses of rods and Muller cells. After correction for the response time of the K(+)-selective microelectrode, the waveforms of all three of these responses were almost exactly as predicted by an earlier computer simulation of the K+/Muller cell hypothesis of the b-wave by Newman and Odette [Newman, E.A. & Odette, L.L. (1984) J. Neurophysiol. 51, 164 182]. The distal K+ increase and the b-wave varied in a similar manner as a function of stimulus irradiance. Superfusion with 0.2 mM Ba2+ attenuated both the Muller cell depolarization and the b-wave by approximately 65% but had no significant effect upon the distal K+ increase. Because Ba2+ reduces K+ conductance of Muller cells, these results are very strong support of the K+/Muller cell hypothesis of the origin of the electroretinogram b-wave; the light-evoked increase in extracellular potassium concentration still is present during superfusion with Ba2+, but the K(+)-evoked Muller cell depolarization and the b-wave are decreased in amplitude because Muller cell K+ conductance is reduced. PMID- 2107545 TI - Recognition by CD8 on cytotoxic T lymphocytes is ablated by several substitutions in the class I alpha 3 domain: CD8 and the T-cell receptor recognize the same class I molecule. AB - The CD8 molecule on class I-reactive cytotoxic T lymphocytes (CTLs) is believed to function as a coreceptor along with the alpha beta T-cell receptor. Whereas the alpha beta T-cell receptor recognizes polymorphic residues in the alpha 1/alpha 2 domains of the class I molecule, the CD8 molecule is believed to recognize monomorphic class I residues. Our previous experiments suggested that residue 227 in the alpha 3 domain of major histocompatibility complex class I molecules contributes to the determinant recognized by CD8. By using a panel of site-directed mutants of H-2Dd, this observation has been extended herein. Our findings indicate that for recognition by CD8-dependent CTLs, residue 227 must be either glutamic acid or aspartic acid and cannot be either basic or uncharged. However, the recognition by CD8-independent CTLs is unaffected by any of the substitutions at position 227 of H-2Dd. Similarly, alterations of other charged residues at positions 222, 223, and 229 have an analogous effect to substitution at residue 227, whereas substitutions at residues 192 and 232 do not affect the reactivity of CD8-dependent or CD8-independent CTLs. In addition, mutant H-2Dd molecules that are not recognized by CD8-dependent CTLs are unable to stimulate a primary CTL response, yet they can stimulate a secondary CD8-independent H-2Dd specific CTL response. These findings suggest that CD8 recognition is obligatory for the priming of class I-dependent CTL responses. Since endogenous class I molecules were expressed by all of the transfected cell lines, these findings provide direct genetic evidence that CD8 and the alpha beta T-cell receptor must interact with the same class I molecule. PMID- 2107546 TI - Molecular characterization of the terminal energy acceptor of cyanobacterial phycobilisomes. AB - Cyanobacteria harvest light energy through multimolecular structures, the phycobilisomes, regularly arrayed at the surface of the photosynthetic membranes. Phycobilisomes consist of a central core from which rods radiate. A large polypeptide (LCM, 75-120 kDa) is postulated to act both as terminal energy acceptor and as a linker polypeptide that stabilizes the phycobilisome architecture. We report here the characterization of the gene (apcE) that encodes this LCM polypeptide in Calothrix sp. PCC 7601. It is located upstream from the genes encoding the major components of the phycobilisome core (allophycocyanin) and is part of the same operon. The deduced amino acid sequence shows that the N terminal region of LCM shares homology with the other phycobiliprotein subunits and thus constitutes the chromoprotein domain. The other part of the molecule is made up of four repeated domains that are highly homologous to the N-terminal regions of the phycocyanin rod linker polypeptides. The predicted secondary structure of the different domains of the LCM is discussed in relation to the different roles and properties of this large molecule. PMID- 2107547 TI - Essential 170-kDa subunit for degradation of crystalline cellulose by Clostridium cellulovorans cellulase. AB - The cellulase complex from Clostridium cellulovorans has been purified and its subunit composition determined. The complex exhibits cellulase activity against crystalline cellulose as well as carboxymethylcellulase (CMCase) and cellobiohydrolase activities. Three major subunits are present with molecular masses of 170, 100, and 70 kDa. The 100-kDa subunit is the major CMCase, although at least four other, minor subunits show CMCase activity. The 170-kDa subunit has the highest affinity for cellulose, does not have detectable enzymatic activity, but is necessary for cellulase activity. Immunological studies indicate that the 170-kDa subunit is not required for binding of the catalytic subunits to cellulose and therefore does not function solely as an anchor protein. Thus this core subunit must have multiple functions. We propose a working hypothesis that the binding of the 170-kDa subunit converts the crystalline cellulose to a form that is capable of being hydrolyzed in a cooperative fashion by the associated catalytic subunits. PMID- 2107548 TI - Selective amplification of an mRNA and related pseudogene for a human ADP ribosylation factor, a guanine nucleotide-dependent protein activator of cholera toxin. AB - ADP-ribosylation factors (ARFs) are approximately 20-kDa proteins that act as GTP dependent allosteric activators of cholera toxin. With deoxyinosine-containing degenerate oligonucleotide primers corresponding to conserved GTP-binding domains in ARFs, the polymerase chain reaction (PCR) was used to amplify simultaneously from human DNA portions of three ARF genes that include codons for 102 amino acids, with intervening sequences. Amplification products that differed in size because of differences in intron sizes were separated by agarose gel electrophoresis. One amplified DNA contained no introns and had a sequence different from those of known ARFs. Based on this sequence, selective oligonucleotide probes were prepared and used to isolate clone psi ARF 4, a putative ARF pseudogene, from a human genomic library in lambda phage EMBL3. Reverse transcription-PCR was then used to clone from human poly(A)+ RNA the cDNA corresponding to the expressed homolog of psi ARF 4, referred to as human ARF 4. It appears that psi ARF 4 arose during human evolution by integration of processed ARF 4 mRNA into the genome. Human ARF 4 differs from previously identified mammalian ARFs 1, 2, and 3. Hybridization of ARF 4-specific oligonucleotide probes with human, bovine, and rat RNA revealed a single 1.8 kilobase mRNA, which was clearly distinguished from the 1.9-kilobase mRNA for ARF 1 in these tissues. The PCR provides a powerful tool for investigating diversity in this and other multigene families, especially with primers targeted at domains believed to have functional significance. PMID- 2107549 TI - Tissue and strain-specific patterns of endogenous proviral hypomethylation analyzed by two-dimensional gel electrophoresis. AB - Proviral sequences related to the intracisternal A particle (IAP) are amplified and dispersed in the mouse genome. Their expression is associated with hypomethylation at CpG sites in the 5' long terminal repeat. We have used two dimensional agarose gel electrophoresis to examine patterns of IAP hypomethylation in mouse DNA. The method is sensitive to both the methylation status of a conserved Hae II site in the 5' long terminal repeat and the location of the closest BamHI site in the flanking DNA upstream of each hypomethylated long terminal repeat. The method also defects restriction fragments derived from IAP elements that are themselves methylated but have an unmethylated Hae II site in their 5' adjacent DNA. DNAs from each of four inbred mouse strains (BALB/c, C3H/He, C57BL/6, and DBA/2) gave distinctive two-dimensional patterns of BamHI/Hae II restriction fragments detected by hybridization with an IAP probe. This constitutive pattern was largely conserved among several tissues of each strain, but some tissue-specific variations were observed. The site-specific hypomethylations reflected in the two-dimensional patterns were heritable properties, since DNA from progeny of an interstrain cross contained both parental sets of fragments. IAP elements may be useful endogenous reporters of genomic methylation patterns. PMID- 2107551 TI - A signaling role for the cytoplasmic segment of the CD8 alpha chain detected under limiting stimulatory conditions. AB - To test for the functional importance of the cytoplasmic segment of the CD8 molecule, a mouse T-cell hybridoma expressing a T-cell receptor specific for the class I major histocompatibility complex product H-2Kb was transfected with a set of CD8 alpha-chain (Ly-2) and/or beta-chain (Ly-3) genes encoding polypeptides with carboxyl-terminal truncations or substitutions. When challenged with Kb positive splenocytes, transfectants expressing Ly-2 homodimers that lacked cytoplasmic tails responded nearly as effectively as wild-type Ly-2 transfectants. However in marked contrast to the wild-type Ly-2 transfectants, tailless Ly-2 transfectants were greatly impaired in their ability to respond to Kb-transfected L cells. Coexpression of the Ly-3 gene did not restore this impaired response. The unique functional property of the Ly-2 alpha cytoplasmic segment was further supported by the analysis of a chimeric Ly-3 subunit in which the cytoplasmic segment was replaced by the one from the Ly-2 alpha subunit. When associated with a soluble Ly-2 subunit lacking a transmembrane segment, the chimeric Ly-3 was indeed sufficient to restore the response to Kb-transfected L cells. Since the lateral mobility of the tailless Ly-2 molecules on the cell surface was nearly identical to that of the wild-type Ly-2 molecules, their partially impaired function may indicate that they have lost their cis-acting signaling properties but retained their ability to bind class I products of the major histocompatibility complex. PMID- 2107550 TI - Molecular cloning of beta 3 subunit, a third form of the G protein beta-subunit polypeptide. AB - The signal-transducing guanine nucleotide-binding regulatory (G) proteins are heterotrimers composed of three subunits--alpha, beta, and gamma. Although multiple distinctive forms of the alpha subunit have been described, only two forms of the beta subunits of the G proteins have been identified. To investigate further the structural diversity of the beta subunits, we screened bovine and human retina cDNA libraries and isolated clones encoding three distinct types of G protein beta subunit. One form was identical to previously isolated beta 1 subunit cDNA clones that encode the 36-kDa form of the beta subunit, whereas a second form was identical to previously described beta 2 cDNAs that encode the 35 kDa beta isoform. In addition, we identified another species, designated beta 3 subunit, which encodes a third distinct form of the beta subunit. The beta 3 subunit cDNA corresponds to a 2.0-kilobase mRNA expressed in all tissues and clonal cell lines examined. Nucleotide sequence analysis indicates that the encoded peptide consists of 340-amino acid residues with a Mr of 37,221. The amino acid sequences of the three beta subunits are closely related: 83% identity between beta 1 and beta 3 subunits and 81% identity between beta 2 and beta 3 subunits. By contrast, the 3'-untranslated regions of the three cDNAs show no significant homology. Our data support the hypothesis that a family of beta subunit polypeptides exists and extend understanding of beta-subunit structure. PMID- 2107552 TI - Interspecies comparisons of in vitro hepatocarcinogenesis. PMID- 2107553 TI - Amino acids and memory consolidation in the cricket. II: Effect of injected amino acids and opioids on memory. AB - The effect of injections of selected amino acids on memory, given before a maze learning, was investigated. Thirsty crickets (Pteronemobius sp.) were trained to turn only to one side of a symmetrical Y-shaped maze using reinforcements with water. The insects retained the learned task 24 hr later. N2 anoxia applied immediately after training produced retrograde amnesia. Injections of Ala, Arg, Gln or morphine prior to training blocked the amnesic action of anoxia, whereas those of Cys, Met, Pro, Orn, octopamine or naloxone did not. Naloxone blocked long-term memory formation, but not learning, whereas Pro and Orn blocked both. The antiamnesic effect of morphine and Arg, but not that of Ala, was blocked by naloxone. A hypothesis assigning a neuromodulatory role to some amino acids is put forward. PMID- 2107554 TI - Experience affects cortical but not subcortical polyamines. AB - The effect of brief periods of experience in an enriched environment (7 hours per day for 3 days), and of inhibition of polyamine synthesis was studied in four brain regions: occipital cortex, remaining cortex, subcortex and cerebellum plus medulla. Polyamine synthesis was inhibited by alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. DFMO caused a 30 50% decrease in putrescine content in all brain areas, irrespective of the environmental treatment. Spermidine was decreased by the inhibitor in subcortex and in cerebellum plus medulla, while spermine was increased in remaining cortex. The regional differences in inhibitor effect suggest that the regulation of polyamine metabolism varies among the four brain areas. Experience increased the weight and spermidine content of remaining cortex and decreased putrescine content of occipital cortex. Noncortical areas were not affected. The effects of experience on polyamine levels were somewhat increased by DFMO. Therefore, experience did not have a generalized effect on polyamine levels; rather, each polyamine responded in a specific manner. In addition, polyamine levels were affected only in those brain areas which are known from previous studies to respond to environmental stimulation with weight increase. These facts suggest that polyamines might have a role in the regulation of experience-induced plasticity. PMID- 2107555 TI - Pharmacological manipulation of anxiety and male rat sexual behavior. AB - Several anxiolytic/anxiogenic treatments were evaluated on male rat sexual behavior. The anxiolytic drug diazepam (1.0 mg/kg) inhibited copulatory behavior as indicated by an increase in the number of mounts preceding ejaculation, prolongation of the ejaculation latency and the postejaculatory interval. These changes were not accompanied by alterations in motor coordination as tested on a treadmill apparatus. A lower dose of diazepam (0.5 mg/kg) did not affect the sexual behavior. The anxiogenic drug Zk 39106 (2 and 4 mg/kg) facilitated the copulatory behavior by reducing the number of intromissions preceding ejaculation. A higher dose of Zk 39106 (8 mg/kg) inhibited sexual behavior. The selective benzodiazepine antagonist, Ro 15-1788 (5 and 10 mg/kg), did not modify male sexual behavior, but effectively antagonized the effects of Zk 39106 and diazepam. The administration of Zk 39106 (2 mg/kg) reversed the inhibitory action of diazepam (1.0 mg/kg) on copulation; however, diazepam did not prevent the facilitory effect of Zk 39106. The data are discussed in terms of the possible relationship existing between anxiety and masculine sexual behavior. PMID- 2107556 TI - Stimulation of DNA synthesis in human epidermis by UVB radiation and its inhibition by difluoromethylornithine. AB - The purpose of this study was to determine whether the rate of DNA synthesis in human skin could be increased by UVB radiation and to determine the potential for reversing the stimulatory effects of UVB radiation by alpha difluoromethylornithine (DFMO). Split-thickness facial skin was grafted onto athymic CD-1 Nu/Nu mice on the anterolateral dorsal surface. Following graft healing for 6 weeks, grafts were treated with 0%, 2%, or 5% DFMO (a potent inhibitor of polyamine biosynthesis) and subsequently irradiated with 0.15 J/cm2 of UVB light. Two days after UVB exposure, [3H]thymidine was injected and the grafts were dissected and counted. Ultraviolet radiation significantly increased thymidine incorporation, indicating increased DNA synthesis. The stimulatory effects of UV radiation were significantly reduced by topical application of 5% DFMO. Thus administration of DFMO most likely decreased the polyamine level and decreased the rate of DNA synthesis, which may have caused a decreased rate of epidermal proliferation. Thus the topical application of DFMO may prove beneficial for UVB exposure and other hyperproliferative states where a decrease in the rate of cell turnover might be desirable. PMID- 2107557 TI - [Experimental possibilities of biological provocation of panic attacks]. AB - On the point of anxiety states, behavioural sciences have only recently been provided with sufficient operational definitions of clinical concepts to enable us to start working on the construction of valid models for the different disorders. Panic attacks are defined as attacks manifested by discrete periods of apprehension or fear, concomitant with at least four marked vegetative sensations, as described in the DSM-III. Several interventions have proved to be able to mimic experimentally such episodes in vulnerable patients, providing the researcher with valuable models for panic research such as the lactate infusion technique, the single CO2 inhalation model and, to a lesser extent, the hyperventilation provocationtest. The study of these models may be a major contribution to a better understanding of panic anxiety, both from a biological and behavioural point of view. Biological observations of those models point to pH changes and ionic shifts as a physiological concomitant in the genesis of experimentally induced panic, and suggests that hypersensitive chemoreceptive structures of the CNS may be implicated. As to the behavioural aspects of the models, there is strong evidence for the ancient phobophobia, or "fear of fear" idea, which may explain the invaldating recurrence of panic attacks. PMID- 2107558 TI - 5-HT1C receptors in the serotonergic control of periaqueductal gray induced aversion in rats. AB - The functional role of brain 5-HT and 5-HT receptor subtypes in periaqueductal gray (PAG) induced aversion has been investigated in rats. Antiaversive effects were found with the serotonin agonists TFMPP, mCPP and DOI but not with RU 24969 which was found to facilitate PAG aversion. The first three serotonin agonists share potent 5-HT1C activity while RU 24969 differs with a high 5-HT1A activity. Proaversive effects were found with the mixed 5-HT1C/5-HT2 antagonists cyproheptadine and ritanserin; this effect was already reported for the mixed 5 HT1C/5-HT2 antagonists metergoline and mianserin and is opposite to the effects of the selective 5-HT2 antagonists ketanserin, pirenperone, trazodone and spiperone. The antiaversive effects of mCPP (1 mg/kg) could be prevented by pretreatment of the animals with mianserin (1 and 10 mg/kg). These results suggest that 5-HT1C receptors play an important role in the serotonergic control of PAG aversion. 5-HT1C receptor activation seems to mediate antiaversive effects whereas acute 5-HT1C receptor blockade appears to facilitate PAG aversion. Functional interactions take place between several receptor types in the in vivo control of PAG aversion, where 5-HT1C receptors appear to play a predominant function. PMID- 2107559 TI - Induction of HSP27 phosphorylation and thermoresistance in Chinese hamster cells by arsenite, cycloheximide, A23187, and EGTA. AB - Incorporation of [3H]leucine, immunochemical analyses with a specific hamster HSP27 rabbit immunoserum, and [32P]orthophosphate labeling were used to monitor synthesis, accumulation, and phosphorylation of HSP27 in Chinese hamster cells after induction of thermoresistance by arsenite, cycloheximide, A23187, and EGTA. In contrast to arsenite-induced thermotolerance, which develops in parallel to synthesis and accumulation of HSP27, enhanced thermoresistance observed immediately after incubating cells in the presence of cycloheximide, A23187, or EGTA is independent of HSP27 or other HSP accumulation. All these treatments, however, result in a rapid phosphorylation of preexisting HSP27. In view of previous results which indicated that HSP27 is involved in cell protection from thermal killing (J. Landry, P. Chretien, H. Lambert, E. Hickey, and L. A. Weber, J. Cell Biol. 109, 7-15, 1989), it is proposed that activation of HSP27 through phosphorylation may be a key determinant in the regulation of cell thermosensitivity. PMID- 2107560 TI - [The antiradiation activity and mechanism of action of dimethylaminodithiazines]. AB - A new group of radioprotective agents, dimethylaminodithiazines, was discovered. The agents are effective when used in relatively small amounts and exert a radioprotective effect rapidly with both intraperitoneal and per os injections. The role of inhibition of oxidative processes and DNA biosynthesis in the mechanism of radioprotective action of dimethylaminodithiazines is discussed. PMID- 2107561 TI - Verification of electron beam therapy with storage phosphor images: precision of field placement. AB - Portal verification images were generated from the photon contamination in electron beams produced by a linear accelerator during treatment of patients receiving high-energy electron radiation therapy (8-14 MeV). An experimental storage phosphor system was used to record the images and display them on laser printed film. Images were obtained from four or more treatment fractions from 21 cases of head and neck cancer. Precision in field placement was estimated by determining the position of a selected anatomic landmark relative to the center of the field for each series of images. The average standard deviation in the field-position measurements was 3.8 mm. Several procedural problems were also detected and corrected after review of the verification images. The results indicate that the emphasis placed on monitoring and control of field-positioning error in high-energy electron treatments should be similar to the emphasis placed on this aspect of error in photon treatment. PMID- 2107562 TI - Thrombolysis for peripheral arterial occlusions. PMID- 2107563 TI - Recombinant tissue-type plasminogen activator versus urokinase in peripheral arterial and graft occlusions: a randomized trial. AB - A randomized prospective trial was undertaken to compare intraarterial administration of recombinant human tissue-type plasminogen activator (rt-PA) with urokinase (UK) in 32 patients with peripheral arterial or bypass graft occlusions. Sixteen patients were randomized to receive rt-PA and 16 to receive UK. The rt-PA dose was administered as a 10-mg bolus into the thrombus, followed by 5 mg/h for up to 24 hours. The UK dose was administered as a 60,000 IU bolus into the thrombus, followed by 240,000 IU/h for 2 hours, 120,000 IU/h for 2 hours, and 60,000 IU/h for up to 20 hours. Serial arteriograms were obtained at baseline and at 4, 8 or 16, and 24 hours. The endpoint was defined as 95% of greater clot lysis. The cumulative numbers of patients with successful thrombolysis (rt-PA vs UK) were four vs none at 4 hours, seven vs one at 8 hours, seven vs three at 16 hours, and eight vs six at 24 hours. Lysis occurred more rapidly in the rt-PA group (P = .04). Major bleeding complications occurred in five rt-PA patients and two UK patients (P = .39). At 24 hours, fibrinogen levels were significantly lower in the rt-PA group than in the UK group (P = .01). There was no apparent difference in 30-day clinical success. PMID- 2107564 TI - Modulation of 3H-prostaglandin E2 binding sites in the rabbit gastric mucosa. AB - The binding of 3H-prostaglandin E2 (PGE2) to rabbit gastric mucosa was investigated. Binding depended on incubation time, temperature and pH, and was saturable and reversible. Scatchard plot analysis revealed a single class of binding sites with a dissociation constant (Kd) of 5.33 +/- 0.21 nM and a maximum number of binding sites (Bmax) of 138.1 +/- 3.4 fmol/mg protein. PGE1 and 16,16 dimethyl PGE2 potently competed with 3H-PGE2 for the binding sites of gastric mucosa, whereas PGA2, PGF2 alpha, 6-keto PGF1 alpha and thromboxane B2 were less potent. The gastric mucosa prepared from the rabbits given indomethacin (5 mg/kg s.c. three times) showed a lower Kd (2.47 +/- 0.19 nM) for 3H-PGE2 than that from untreated one. Treatment with a PGE1 analog, misoprostol (320 micrograms/kg s.c. three times) lowered the Bmax to 74.1 +/- 2.4 fmol/mg protein without any significant effect on the Kd value. It is concluded that rabbit gastric mucosa has specific binding sites for 3H-PGE2 which may be modulated by the levels of PGs in vivo. PMID- 2107565 TI - Glutathione disulfide production during arachidonic acid oxygenation in human platelets. AB - Washed human platelets stimulated with 50 microM sodium arachidonate rapidly accumulated glutathione disulfide to a peak concentration of 0.620 nmole per 10(9) cells, 200% of control (unstimulated) levels. Total glutathione remained unchanged. The rise in glutathione disulfide was transitory, returning to control values within 30 seconds in aggregating platelets. Similar findings were observed in washed platelets aggregated with 5 U/ml thrombin. Platelet aggregation was not necessary for the generation of glutathione disulfide. However, cyclooxygenase activity was necessary for the generation of glutathione disulfide. Aspirin treated platelets aggregated with thrombin demonstrated no thromboxane B2 production and no glutathione disulfide generation. Dose response studies with both agonists demonstrated a direct relationship between the amount of thromboxane B2 produced and the amount of glutathione disulfide generated by stimulated platelets. During the conversion of arachidonic acid to thromboxane B2, unesterified arachidonic acid is oxygenated to prostaglandin G2 which is subsequently reduced to prostaglandin H2. Both reactions are catalyzed by the enzyme prostaglandin H synthase. Our data support the hypothesis that glutathione is an important supplier of reducing equivalents to prostaglandin H synthase during the production of prostaglandin H2 in human platelets. PMID- 2107566 TI - Recovery of prostaglandin synthesis in rat glomerular mesangial cells after aspirin inhibition: induction of cyclooxygenase activity by serum and epidermal growth factor. AB - We assessed cyclooxygenase activity in cultured rat mesangial cells by measuring prostaglandin production with reverse phase HPLC upon addition of exogenous 14C arachidonic acid. The profile of prostaglandins produced was PGE2 greater than PGF2a much greater than 6-keto PGF1a much greater than thromboxane and PGD2. In quiescent mesangial cells, exposure to 300 microM aspirin for 30 minutes irreversibly inhibited cyclooxygenase activity; after 5 hours, cyclooxygenase activity was only 19 +/- 3% of control. Addition of 10% fetal bovine serum after aspirin inactivation stimulated time-dependent recovery of cyclooxygenase activity to 118 +/- 30% of control by 5 hours. Serum induced-recovery was significantly inhibited by the simultaneous administration of the protein kinase C inhibitor, staurosporine. Phorbol myristate acetate also induced recovery of cyclooxygenase activity, suggesting that protein kinase C may be involved in the signaling process. In addition to serum, epidermal growth factor was also found to lead to partial recovery of cyclooxygenase activity. The serum and EGF-induced recoveries were inhibitable by cycloheximide and actinomycin D. These results suggest that recovery of cyclooxygenase activity in mesangial cells is stimulated by EGF and other components of serum, is dependent upon new protein synthesis and appears to be transcriptionally regulated. PMID- 2107567 TI - [Analysis and analyzing as reflected in an empirical study]. AB - The authors compare two investigations--the findings of the prognostic study concerning psychotherapeutic service delivery in the FRG and a follow-up study carried out among the members of the German Psychoanalytic Association. The former showed that high-frequency long-term analysis is the exception rather than the rule, and the findings of the latter differ only slightly from this determination. PMID- 2107568 TI - Regulation and control of bicarbonate reabsorption in the proximal tubule. PMID- 2107569 TI - H+/base transport in the proximal straight tubule and thin descending limb of Henle. PMID- 2107570 TI - Update on pancreatic islet cell transplantation. AB - The biological validation of islet grafts would free total pancreas resection from the onus of severe diabetes mellitus. Islet cell transplants can reverse diabetes mellitus and prevent complications in animal models. Immune rejection has foiled attempts at human transplantation despite moderate success with whole pancreas grafts. Aggressive rejection of islet grafts has been extensively studied in animal models and seems no different in substance from standard cell mediated rejection but vastly different in tenacity. Rejection cannot be prevented by immunosuppression strategies effective for transplantation of heart, kidney, or liver. New strategies to circumvent islet rejection include encapsulation of the islets to obfuscate immune recognition, pretreatment of the islets in vitro to reduce immunogenicity, donor manipulation to provide specific tolerance, and combination strategies. In the development of these strategies, much has been learned or confirmed about the nature of immune rejection, and another round of human trials can be anticipated. PMID- 2107571 TI - What the brain tells the eye. PMID- 2107572 TI - A case of heavy chain disease: diagnosis and monitoring using assays of immunoglobulin heavy and light chains. AB - Heavy chain diseases (HCD) are uncommon. We report the first use of recently developed analytical techniques for the assay of immunoglobulin heavy and light chains in the diagnosis and monitoring of a patient with gamma-HCD. PMID- 2107573 TI - Ribozymes as potential anti-HIV-1 therapeutic agents. AB - Certain RNA molecules, called ribozymes, possess enzymatic, self-cleaving activity. The cleavage reaction is catalytic and no energy source is required. Ribozymes of the "hammerhead" motif were identified in plant RNA pathogens. These ribozymes possess unique secondary (and possibly tertiary) structures critical for their cleavage ability. The present study shows precise cleavage of human immunodeficiency virus type 1 (HIV-1) sequences in a cell-free system by hammerhead ribozymes. In addition to the cell-free studies, human cells stably expressing a hammerhead ribozyme targeted to HIV-1 gag transcripts have been constructed. When these cells were challenged with HIV-1, a substantial reduction in the level of HIV-1 gag RNA relative to that in nonribozyme-expressing cells, was observed. The reduction in gag RNA was reflected in a reduction in antigen p24 levels. These results suggest the feasibility of developing ribozymes as therapeutic agents against human pathogens such as HIV-1. PMID- 2107574 TI - Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. AB - Major epidemic outbreaks of viral hepatitis in underdeveloped countries result from a type of non-A, non-B hepatitis distinct from the parenterally transmitted form. The viral agent responsible for this form of epidemic, or enterically transmitted non-A, non-B hepatitis (ET-NANBH), has been serially transmitted in cynomolgus macaques (cynos) and has resulted in typical elevation in liver enzymes and the detection of characteristic virus-like particles (VLPs) in both feces and bile. Infectious bile was used for the construction of recombinant complementary DNA libraries. One clone, ET1.1, was exogenous to uninfected human and cyno genomic liver DNA, as well as to genomic DNA from infected cyno liver. ET1.1 did however, hybridize to an approximately 7.6-kilobase RNA species present only in infected cyno liver. The translated nucleic acid sequence of a portion of ET1.1 had a consensus amino acid motif consistent with an RNA-directed RNA polymerase; this enzyme is present in all positive strand RNA viruses. Furthermore, ET1.1 specifically identified similar sequences in complementary DNA prepared from infected human fecal samples collected from five geographically distinct ET-NANBH outbreaks. Therefore, ET1.1 represents a portion of the genome of the principal viral agent, to be named hepatitis E virus, which is responsible for epidemic outbreaks of ET-NANBH. PMID- 2107575 TI - Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. AB - The function of the heart depends critically on an adequate oxygen supply through the coronary arteries. Coronary arteries dilate when the intravascular oxygen tension decreases. Hypoxic vasodilation in isolated, perfused guinea pig hearts can be prevented by glibenclamide, a blocker of adenosine triphosphate (ATP) sensitive potassium channels, and can be mimicked by cromakalim, which opens ATP sensitive potassium channels. Opening of potassium channels in coronary smooth muscle cells and the subsequent drop in intracellular calcium is probably the major cause of hypoxic and ischemic vasodilation in the mammalian heart. PMID- 2107576 TI - [Depressed fracture of the calvaria]. AB - This study is based on 147 depressed fractures of the calvaria. 60% of the diagnosed and treated cases were compound depressed fractures. Of the 147 patients 12 developed intracerebral, epidural and subdural hematomas. 3 persons developed infections. Of course the decision to institute prophylactic anticonvulsive therapy we only found 7 cases of posttraumatic epilepsy. Because of our experience in treatment of the depressed fracture we divide a consequent and rapid diagnosis by X-rays in combination with modern computer-tomography. PMID- 2107577 TI - [Ligament reinforcement with resorbable PDS cord and early functional after-care. Results of follow-up of surgically managed cruciate ligament injuries]. AB - After operating on the injured cruciate ligaments, immediate mobilization and protection of the healing ligament are indispensible. However, no approach has yet been shown to safely provide both. Therefore, in 1984 we introduced a new technique: the repaired or reconstructed cruciate ligaments are augmented with a biodegradable material - a doubled-over PDS cord, 1.5 mm in diameter. It allows for immediate and safe mobilization. Because of its appropriate elasticity it does not cause "stress shielding." Postoperatively, the patients are mobilized on a motorized frame for 2 weeks. Subsequently, we have used a limited mobilization cast (LMC). Forty-nine out of 63 patients (78%) have now been reexamined for this follow-up study, using the score from the Hospital for Special Surgery and stress X-rays in the Lachmann, position (30 degrees flexion). The results compare favorably with a prior follow-up study of patients from our hospital without PDS augmentation and without early mobilization. The knees in the present study are more stable and have a better range of motion, particularly when the LMC was used. PMID- 2107578 TI - Flat on your back or back to your flat? Sources of increased hospital services utilization among the elderly in British Columbia. AB - Between 1969 and 1985, the British Columbia hospital system allocated an increasing proportion of the province's total hospital days to elderly patients who stayed for 60 days or more. By 1985/86, long stay patients accounted for almost 50% of all days. In this paper, we explore the diagnoses which contributed the greatest number of patient days of increase among the elderly as a first step in evaluating the appropriateness of this response to the pressures of an aging population. Patient days of increase were not distributed smoothly across a large number of diagnoses, but could be explained by a small number of chronic conditions. Most important were conditions related to senility and senile dementia, the chronic sequelae of heart disease and stroke, and persons awaiting admission to adequate facilities elsewhere. Eighty percent of the increases were seen in extended care and rehabilitation beds and 20% in acute care beds. Seventy seven percent of the increased patient days were attributable to females and only 23% to males. Since the major sources of increase in patient days were not related to conditions for which new, effective hospital care modalities are available, they call into question the appropriateness of the system's response to the health care needs of the elderly population. PMID- 2107579 TI - Hypoxia and hypercarbia of chronic lung disease: minimal effects on anterior pituitary function. AB - Previous studies have suggested that the hypoxia and/or hypercapnia associated with chronic lung diseases may lead to pituitary and gonadal dysfunction, with destruction of the sella turcica. It is unclear, however, whether these abnormalities were due to lung disease or to confounding factors. We studied the relationships between hormonal levels (triiodothyronine, thyroxine, T3 resin uptake, thyrotropin, prolactin, cortisol, and testosterone) and PaO2, PaCO2, pH, and alveolar-arterial gradient in 25 patients with chronic lung disease. These patients were highly homogeneous for diagnosis, age, sex, ambulatory status, lack of other illnesses, and minimal use of medications unrelated to lung disease, but did have various degrees of hypoxia and hypercarbia at the time of study. We found no relationship between hormonal levels and lung function, or evidence of major pituitary involvement on lateral roentgenograms of the skull, CT of the sella turcica, or stimulation of the pituitary. An inverse correlation did occur between serum levels of thyroxine and the daily dose of oral prednisone. We conclude that most of the endocrine dysfunction ascribed to chronic lung diseases is probably due to factors other than hypoxia or hypercarbia. PMID- 2107580 TI - Massive bleeding in a Zenker's diverticulum. AB - Massive bleeding from a pharyngoesophageal diverticulum is a rarely reported condition, with only two reported cases in the literature. This report describes a patient who had massive bleeding due to ulceration in the base of a pharyngoesophageal diverticulum, presumed to have been caused by chronic aspirin ingestion. The diagnosis was made on upper gastrointestinal endoscopy, and surgical treatment (cricopharyngeal myotomy and diverticulectomy) was curative. PMID- 2107581 TI - Combination of a thiazide, a vasodilator and reserpine compared with methyldopa plus hydrochlorothiazide in the treatment of hypertension in Zimbabwe. AB - Brinerdin (Sandoz), a combination of a diuretic (clopamide 5 mg), a vasodilator (dihydro-ergocristine 0.5 mg) and reserpine (0.1 mg) (CDR) was compared with methyldopa (MD) plus hydrochlorothiazide (HCT) for antihypertensive effect, adverse reactions, compliance and patient preference in an open cross-over trial. Eighteen patients completed both arms of the trial and 5 patients who completed the CDR arm were withdrawn while on the MD arm because of adverse effects in 4 and poor control in 1. On HCT 50 mg daily the mean baseline systolic blood pressure was 163.9 +/- 16.3 mmHg and the diastolic blood pressure was 105.9 +/- 6.7 mmHg. On CDR these were reduced to systolic blood pressure 140.3 +/- 15.1 mmHg and diastolic blood pressure 87.8 +/- 9.3 mmHg. On MD + HCT the systolic blood pressure was reduced to 138.5 +/- 16.9 mmHg and the diastolic blood pressure to 88.9 +/- 10.3 mmHg. The differences between the two treatment periods in systolic blood pressure (1.8 mmHg; 95% confidence interval (CI) - 4.1 + 7.7 mmHg) and diastolic blood pressure (1.1 mmHg; 95% CI - 4.6 + 2.4 mmHg) were not significant with P values of 0.6 and 0.7 respectively. Compliance was 98.2% for CDR and 94.7% for MD + HCT (P = 0.02). Unusual sleepiness occurred more frequently in the MD arm (P less than 0.01). Thirteen patients chose to continue on CDR, 2 on MD + HCT and 3 had no preference (P = 0.005). CDR is similar in antihypertensive effect to MD + HCT but is better tolerated with fewer withdrawals, fewer adverse effects, better compliance and has more patients electing to continue taking it. PMID- 2107582 TI - Schistosomiasis of the spinal cord--underdiagnosed in South Africa? AB - Schistosomiasis is endemic in many areas of South Africa, particularly the northern and eastern Transvaal. At Ga-Rankuwa Hospital in the northern Transvaal, 30 km north-west of Pretoria, spinal cord disease is common. In a substantial proportion of these cases no obvious cause for the condition can be found. In an attempt to draw attention to schistosomiasis as a possibly underdiagnosed cause of spinal cord disease, 3 cases of schistosomiasis of the spinal cord seen over a period of 3 years are reported. These 3 patients had histological evidence of spinal schistosomiasis. Because myelography of the spinal cord is often non contributory in schistosomal involvement, it is suggested that patients with 'myelopathy of unknown origin' who come from an endemic area be given a therapeutic trial of praziquantel, especially if the serological findings are positive for schistosomiasis and the lower cord is involved. PMID- 2107583 TI - The value and cost-effectiveness of a home-visiting programme for psychiatric patients. AB - The high rate of readmissions to psychiatric hospitals constitutes a considerable problem. An attempt to reduce these by a controlled standard home-visiting procedure was carried out for 51 consecutive patients at Valkenberg Hospital, Cape Town. Readmissions were reduced by 31.5% over 1 year and the number of days in hospital by 55.6% from 3714 to 1850 days. Attendance at outpatient clinics also improved by 39%. The cost-effectiveness of this programme was also demonstrated; there was a saving of approximately R786 per patient over the year. PMID- 2107584 TI - Pharmacologic response of endothelium to microvascular temporary clip application. AB - To assess the effects of microvascular temporary clip application on vessel relaxing capability and endothelial substance release, the carotid rings of rats clipped for various durations were studied via bioassay. Noradrenaline and phenylephrine produced an immediate contraction and subsequent relaxation that failed to be suppressed by lysine acetylsalicylate or nicotine in the controls and in the arteries clipped for 0.5, 1, and 5 minutes; however, this relaxation was greatly reduced when the duration was 10 minutes. The results suggest the possible role of inadequate endothelium-derived relaxing factor release following prolonged application of the clips. PMID- 2107585 TI - [Secondary malignomas following radiotherapy of breast carcinoma: a case report]. AB - Numerous cases of radiation-induced malignoma have been described, where the radiation osteosarcomas are placed in the foreground. In this article a case of a female patient is described who developed not only a radiation-induced osteosarcoma but also a thyroid gland carcinoma after a previous postsurgical mamma carcinoma whereby the irradiation dose of the radiation sarcoma is about 64 Gy and for the thyroid gland carcinoma about 12 Gy. PMID- 2107586 TI - Applicability of LLD in neutron dosimetry. AB - The applicability of LLD in neutron dosimetry was tested and the optimum materials were determined. Investigations have been performed on lyoluminescence variations in sensitivity (X-rays and neutrons) for five different materials: the polyalcohols, mannitol and xylitol, the saccharides, trehalose and glucose and the amino acid, leucine. The decisive factor for the choice of a dosimetric material is its tissue equivalence. The results show striking differences in neutron and gamma sensitivities between the dosimetric materials. The different sensitivities for fast neutrons and gamma-rays can be used for simultaneous determination of neutron and gamma doses in mixed neutron photon radiation fields. The successful application of this dosimetric method can be shown by phantom- and in-vivo-measurements. PMID- 2107587 TI - [We can create a special public hospital]. PMID- 2107588 TI - [The long-term management of heart transplant patients]. AB - The long-term care of patients following heart transplantation is characterized by the problems associated with long-term immunosuppression. In addition, a specific form of coronary atherosclerosis develops within years in many patients requiring coronary angiography on a yearly basis. The examination of patients after heart transplantation does not reveal characteristic findings, as long as the transplanted heart functions properly and a normally functioning graft allows a functionally almost normal life. The dependence on a specialized center, which may be more or less depending on the clinical course, and the ever present knowledge of the potentially lethal consequences of a graft failure present a severe psychic stress to the patient. This stress is handled more or less well and requires special attention by the treating physicians and, ideally, an intact social environment. The care of patients in a center close to their place of living is less time consuming for the patient and relieves the burden of the transplanting center. PMID- 2107589 TI - Pulmonary gamma interferon production in patients with fibrosing alveolitis. AB - Patients with fibrosing alveolitis have active inflammation within their lung interstitium. Previous studies have focused on the humoral (immune complex) driven processes. In this study increased pulmonary gamma interferon production has been evaluated. Bronchoalveolar lavage cells were obtained from 40 patients with fibrosing alveolitis, 22 with cryptogenic fibrosing alveolitis, and 18 with connective tissue disease associated (CTD) fibrosing alveolitis. Increased gamma interferon production was seen in 12 (30%) patients and was similar in the two study groups. Up to 512 units/10(6) cells were released over 24 hours, showing that the amounts of gamma interferon released could be as large as those seen in other pulmonary diseases associated with active cellular immune processes, such as sarcoidosis. Spontaneous gamma interferon production was related to increased serum concentrations of IgG and IgM but not to serum IgA, antinuclear antibody, or rheumatoid factor titres. There was no relation between gamma interferon production and pulmonary uptake of gallium-67 citrate. The ratio of helper inducer (Leu-3) to suppressor-cytotoxic (Leu-2) cells in bronchoalveolar lavage fluid was similar in the two study groups and was similar in patients whose cells produced gamma interferon and those whose cells did not. These data suggest that gamma interferon is released in the lungs of a proportion of individuals with cryptogenic fibrosing alveolitis and CTD-fibrosing alveolitis, suggesting a role for this cytokine in mediating these diseases. PMID- 2107590 TI - Quantitation of anticephalin antibodies in a computer-assisted enzyme-linked immunosorbent assay (ELISA): relation to lupus anticoagulant. AB - Lupus anticoagulants (LA) are IgG or IgM antibodies which prolong phospholipid dependent coagulation tests. For the detection and quantitation of such antibodies, we have developed an ELISA with cephalin as the coating antigen. The sensitivity of this assay was compared to the activated partial thromboplastin time (APTT). LA was defined as greater than or equal to 5 sec prolongation of the APTT with standard cephalin dilution, or greater than or equal to 10 sec prolongation with a high cephalin dilution, on a 1:1 mixture of patient and control plasma. Plasma samples from 158 healthy individuals were tested for anticephalin antibodies. The 97.5 percentile was chosen as the upper reference limit and allocated a value of 1 ELISA unit. A "four-parameter logistic" model was used for transformation of the absorbances to ELISA units. Of 314 plasma samples referred for LA screening, positive results were found in 62 by both APTT and ELISA. Twenty-three samples were ELISA positive and APTT negative; this finding may be explained by greater sensitivity of the ELISA, which gave positive results in a four-fold greater dilution than the APTT. Prolongation of the APTT without antibody activity was found in 8 samples of which 2 had an inhibitor of factor VIII:C, the remaining 6 probably had true LA. In conclusion, our computer assisted ELISA is a sensitive and reliable test method for quantitation of anticephalin antibodies. This assay has a high concordance with LA as detected with the APTT. PMID- 2107591 TI - Impairment of the protein C anticoagulant pathway in a patient with systemic lupus erythematosus, anticardiolipin antibodies and thrombosis. AB - We have identified an inhibitor of the protein C anticoagulant pathway in the plasma of a patient with systemic lupus erythematosus and a history of recurrent deep vein thrombosis, fetal wastage, and seizures. The patient's plasma contained anticardiolipin antibodies as well as a weak lupus anticoagulant. Examination of this patient's plasma revealed normal levels of protein C and protein S antigen, normal levels of functional protein C, as well as essentially normal levels of every blood coagulation factor. In a modified prothrombin time assay, the activated protein C-mediated prolongation of the clotting time observed in normal plasma was not observed in this patient's plasma. Gel permeation chromatography of the patient's plasma revealed that the inhibitory material was a high molecular weight protein that coeluted with the IgM peak. The inhibitor did not appear to circulate as a complex with protein C, since the inhibitor could easily be separated from protein C during fractionation procedures, and did not interfere with the activation of protein C in plasma as assessed by a functional amidolytic assay. Our findings suggest that the recurrent thrombotic episodes observed in this patient may have occurred as a result of the patient's antiphospholipid antibody neutralizing specific phospholipids essential for the full expression of the anticoagulant activity of activated protein C. PMID- 2107592 TI - Prothrombin-antibody coexistent with lupus anticoagulant (LA): clinical study and immunochemical characterization. AB - The patient is a 23 y.o. man with acute nephritis and bleeding at presentation. Laboratory data consistent with the diagnosis of systemic lupus erythematosus. A lupus anticoagulant was found: tissue thromboplastin inhibition test (TTIT) ratio 3.4; diluted Russell viper venom (DRVV) ratio 2.6. Hypoprothrombinemia (FII:C less than 1%; FIIR:Ag 5%) was present; prothrombin survival time (FII concentrate infusion 60 U/kg): t1/2 approximately to 9 hours. A prothrombin antibody was identified: it is not neutralizing but forms an immunecomplex with prothrombin. The antibody was characterized as IgG2, IgA, k, lambda. The prothrombin survival time indicates that the hypoprothrombinemia is due to the clearance of the prothrombin-antiprothrombin complex in vivo. PMID- 2107593 TI - Effect of fibrin-targeting on clot lysis with urokinase-type plasminogen activator. AB - The effect of fibrin-targeting of urokinase-type plasminogen activator (u-PA) on its fibrinolytic potency was studied using recombinant fusion proteins of u-PA with the NH2-terminal region of tissue-type plasminogen activator (t-PA/u-PA) and chemical complexes of u-PA with F(ab')2 fragments of a fibrin specific monoclonal antibody (u-PA/MA-15C5-F(ab')2). Two chain derivatives of a low Mr variant of u PA comprising amino acids Leu144-Leu411 (tcu-PA-32k), obtained by cleavage of recombinant single-chain u-PA (rscu-PA-32k) with thrombin (rtcu-PA-32k/T) or plasmin (rtcu-PA-32k/P) were investigated. The plasmin-derived two chain u-PA moieties, rtcu-PA-32k/P, rt-PA/tcu-PA-32k/P and rtcu-PA-32k/MA-15C5-F(ab')2/P had high specific activities in amidolytic and fibrin plate assays (130,000 and 150,000 IU/mg u-PA, 43,000 and 71,000 IU/mg u-PA and 32,000 and 56,000 IU/mg u-PA respectively). The thrombin-derived two chain u-PA moieties had a very low amidolytic activity, corresponding to less than or equal to 1 percent of that of their plasmin-derived counterparts. On fibrin plates, however, rtcu-PA-32k/T had a negligible activity, whereas rt-PA/tcu-PA-32k/T and rtcu-PA-32k/MA-15C5 F(ab')2/T had specific activities of 12,000 and 25,000 IU/mg u-PA respectively. The catalytic efficiency for plasminogen activation of rtcu-PA-32k/MA-15C5 F(ab')2/T is 4,000-fold lower than that of rtcu-PA-32k/MA-15C5-F(ab')2/P, but its concentration required for 50 percent lysis in 2 hours of a 125I-fibrin labeled plasma clot in human plasma (C50) is only 25-fold higher. The catalytic efficiency of rt-PA/tcu-PA-32k/T is 1,600-fold lower and the C50 100-fold higher than that of rt-PA/tcu-PA-32k/P. The catalytic efficiency and the fibrinolytic potential of rtcu-PA-32k/T are negligible as compared to that of rtcu-PA-32k/P. These observations may be explained by conversion of the thrombin derived two chain u-PA moieties to their plasmin-derived analogues at the fibrin surface. This conversion appears to be most efficient for the antibody conjugate which has a high fibrin-affinity, less efficient for the t-PA/u-PA chimera which has only moderate fibrin-affinity, and negligible for the unconjugated u-PA moiety which has no fibrin-affinity. These findings illustrate the importance of plasmin mediated positive feedback mechanisms in u-PA mediated clot lysis. PMID- 2107594 TI - A biological method for studying the interaction between platelets and vascular endothelium. AB - A segment of fresh rabbit thoracic aorta (RbA) was turned inside out and superfused (1.5 ml/min) with citrated (3.8%) or heparinized (10 U/ml) blood of rabbit and the superfusate was discarded. RbA gained in weight due to deposition of thrombi on its endothelial surface. These thrombi were mainly composed of platelets. The interaction between platelets and endothelium was augmented in RbAs from animals with atherosclerosis and in RbAs pretreated with aspirin (110 microM) or 15-HPETE (150 microM) or by the enzymatic system generating oxygen free radicals (xanthine:xanthine oxidase - 100 microM: 0.1 U/ml). On the other hand, this interaction was impaired by superoxide dismutase (20 U/ml) or catalase (0.2 U/ml). Finally, the dissipation of thrombi by thromboxane A2-synthetase inhibitor--dazoxiben was found to be related to an increase in endothelial generation of prostacyclin. PMID- 2107595 TI - Differential inhibition of thromboxane A2 and prostacyclin synthesis by low dose acetylsalicylic acid in atherosclerotic patients. AB - Differential inhibition of thromboxane A2 (TxA2) and prostacyclin (PGI2) biosynthesis has an antithrombotic potential, since it may change the TxA2/PGI2 formation ratio in a favourable direction. Very low doses of acetylsalicylic acid (ASA) have been demonstrated to elicit differential inhibition of TxA2 and PGI2 formation in healthy subjects; whether a similar effect can be obtained in patients with atherosclerosis is still an open question. We addressed this by analyzing the urinary excretion of the 2,3-dinor-metabolites of TxA2 (Tx-M) and PGI2 (PGI-M) in 10 patients with severe atherosclerosis during 10 consecutive days. The first three days were a basal period, under which no treatment was given. During the subsequent seven days a daily 50 mg oral dose of ASA was administered. In the basal state urinary Tx-M did not differ from that of PGI-M, the median excretion rates of the two eicosanoid metabolites being 526 (range 68 1490) and 562 (range 93-1970) pg/mg creatinine, respectively. During ASA treatment urinary Tx-M fell to a lower (p less than 0.001) level than PGI-M. Thus, during the last 5 days of ASA treatment the median excretion of Tx-M was depressed (p less than 0.001) to 148 (range 48-428) pg/mg creatinine, while that of PGI-M was decreased (p less than 0.01) to 313 (range 42-2658) pg/mg creatinine. These data indicate that a daily 50 mg dose of ASA inhibits cardiovascular formation of eicosanoids in patients with severe atherosclerosis and increased platelet TxA2 formation. Furthermore, this dose of ASA inhibits the formation of TxA2 more than that of PGI2. PMID- 2107596 TI - Suppression of plasminogen activator inhibitor 1 release by fibrin from human umbilical vein endothelial cells. AB - The effect of fibrin stimulation on the fibrinolytic potential in cultured human umbilical vein endothelial cells (HUVEC) was investigated in the normal state and aged state. The amount of antigen of the two fibrinolytic factors, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1), was determined using ELISA and the ABC method, respectively. When a fibrin clot was overlayered on the normal HUVEC, the secretion of t-PA or PAI-1 from the HUVEC was greatly changed. That is, PAI antigen was decreased 3-fold and t-PA antigen increased slightly in the conditioned medium. On the other hand, when the aged HUVEC were stimulated by a fibrin clot, PAI antigen was increased 3-fold and t-PA antigen did not change in the conditioned medium. When the level of fibrinolytic activity in the conditioned medium was expressed as the molar ratio of PAI and t PA (PAI/t-PA), the value in the fibrin-stimulated normal HUVEC was markedly reduced (a 3.5-fold decrease) when compared with that of the non-stimulated normal HUVEC, reflecting a profibrinolytic state. On the other hand, the value in the fibrin-stimulated aged HUVEC was markedly increased (a 5-fold increase) when compared with that of the non-stimulated aged HUVEC, reflecting an antifibrinolytic state. Actinomycin D- or cycloheximide-treated HUVEC showed no response to the fibrin stimulation. We conclude that the level of HUVEC-mediated fibrinolytic activity was regulated mainly by the production and secretion of PAI from the HUVEC to protect against the generation of thrombi. In the aged HUVEC, the regulatory mechanism acts in an opposite manner and a thrombotic process may be induced. PMID- 2107597 TI - Degradation of fibrinogen by tissue plasminogen activator. Consequences for fibrin polymerization. AB - In patients treated with tissue plasminogen activator (t-PA), there was a marked increase in concentration of fibrinopeptide A (fpA). The purpose of this study was to analyse the activation of coagulation in plasma treated in vitro by pharmacological doses of t-PA. From our results, it appears that fpA release due to direct interaction of fibrinogen with t-PA, in the absence of plasminogen, is very low and not observed with pharmacological doses of t-PA. In contrast in the presence of plasminogen, the release of fpA is much higher and induces fibrin formation concomitantly to fibrinogen degradation. PMID- 2107598 TI - On the molecular interactions between fibrin, tissue-type plasminogen activator and plasminogen. AB - The molecular interactions involved in the fibrin-mediated stimulation of plasminogen activation by tissue-type plasminogen activator (t-PA) were studied using natural human plasminogen (nPlg) and rPlg-Ala740, a recombinant human plasminogen in which the catalytic site is destroyed by mutagenesis of the active site Ser740 to Ala. Using this rPlg-Ala740 moiety, the dissociation constant of the interaction between plasminogen and CNBr-digested fibrinogen was determined to be 0.40 microM. In addition, conversion of 125I-labeled single chain plasminogen to two chain plasmin by single chain recombinant t-PA (rt-PA) in the absence or the presence of CNBr-digested fibrinogen was quantitated on reduced SDS-gel electrophoresis, combined with autoradiography and radioisotope counting of gel bands. In the absence of fibrin, the activation rate of nPlg and rPlg Ala740 by single-chain rt-PA was comparable. In the presence of fibrin, however, the activation rate of rPlg-Ala740 was about 20-fold lower than that of nPlg. These results with rPlg-Ala740 may be explained by an impaired formation of the stable cyclic ternary complex between plasminogen, t-PA and fibrin, which mediates the fibrin stimulation of plasminogen activation by t-PA or, alternatively, by impaired conversion of single chain rt-PA to two chain rt-PA at the fibrin surface. PMID- 2107599 TI - Receptor-mediated endocytosis of tissue-type plasminogen activator (t-PA) by liver cells. AB - Tissue-type plasminogen activator (t-PA) has a short half-life in the circulation because the enzyme is rapidly cleared by the liver. This short review summarizes recent literature concerning mechanisms of uptake and degradation of t-PA in the liver. In vivo studies in rats show that degradation takes place via a lysosomal pathway. Saturation of the uptake system at high t-PA concentrations suggests a receptor-mediated mechanism. Competition experiments with various glycoproteins indicate that the asialoglycoprotein receptor is not involved, but they point to a role for the mannose receptor, which recognizes t-PA via its high mannose-type oligosaccharide on the first kringle domain. Both in vivo and in vitro studies with isolated liver cells demonstrate that parenchymal cells, as well as liver endothelial cells, are involved in the clearance of t-PA. Parenchymal cells, as the hepatoma cell line Hep G2, endocytose t-PA via a still unknown, possibly t-PA specific receptor, while liver endothelial cells catabolize t-PA via the mannose receptor. PMID- 2107600 TI - Acute myocardial infarction and thrombolytic therapy. PMID- 2107601 TI - Enhancement of fibrinolysis by bispecific monoclonal antibodies reactive to fibrin and plasminogen activators. AB - Murine hybrid hybridomas secreting bispecific monoclonal antibodies (bs mAbs) were constructed by fusing hybridomas secreting an anti-tissue plasminogen activator (tPA) or anti-urokinase (UK) mAb with hybridomas secreting a mAb which binds to human fibrin but not to fibrinogen. The bs mAbs reactive to both fibrin and PA (tPA or UK) were purified by affinity chromatography employing the respective antigen-coupled columns and characterized by fibrin-binding, amidolytic and fibrinolytic assays. Immunochemical conjugation of PAs and the bs mAbs did not impair the catalytic activity of PAs at all and made it possible to concentrate PAs on fibrin clot. Pretreatment of fibrin with the bs mAbs enhanced the fibrin-binding of PAs and the subsequent fibrinolysis. PMID- 2107602 TI - Disposition of three glycol ethers administered in drinking water to male F344/N rats. AB - The glycol ethers 2-methoxyethanol (ME), 2-ethoxyethanol (EE), and 2 butoxyethanol (BE) are widely used solvents in industrial and consumer applications. The reproductive, teratogenic, and hematotoxic effects of the glycol ethers are due to the alkoxyacetic acid metabolites of these compounds. The effect of alkyl group length on disposition of these three glycol ethers was studied in male F344/N rats allowed access for 24 hr to 2-butoxy[U-14C]ethanol, 2 ethoxy[U-14C]ethanol, or 2-methoxy[U-14C]ethanol in drinking water at three doses (180 to 2590 ppm), resulting in absorbed doses ranging from 100 to 1450 mumols/kg body wt. Elimination of radioactivity was monitored for 72 hr. The majority of the 14C was excreted in urine or exhaled as CO2. Less than 5% of the dose was exhaled as unmetabolized glycol ether. Distinct differences in the metabolism of the glycol ethers as a function of alkyl chain length were noted. For BE 50-60% of the dose was eliminated in the urine as butoxyacetic acid and 8-10% as CO2; for EE 25-40% was eliminated as ethoxyacetic acid and 20% as CO2; for ME 34% was eliminated as methoxyacetic acid and 10-30% as CO2. Ethylene glycol, a previously unreported metabolite of these glycol ethers, was excreted in urine, representing approximately 10, 18, and 21% of the dose for BE, EE, and ME, respectively. Thus, for longer alkyl chain lengths, a smaller fraction of the administered glycol ether was metabolized to ethylene glycol and CO2. Formation of ethylene glycol suggests that dealkylation of the glycol ethers occurs prior to oxidation to alkoxyacetic acid and, as such, represents an alternate pathway in the metabolism of these compounds that does not involve formation of the toxic acid metabolite. PMID- 2107603 TI - Influence of streptozotocin (STZ)-induced diabetes, dextrose diuresis and acetone on cisplatin nephrotoxicity in Fischer 344 (F344) rats. AB - The following studies examined the impact of the diabetic state on cisplatin nephrotoxicity. This study also investigated the potential mechanisms for diabetes mediated reduction of cisplatin toxicity. A diabetic state was induced in male Fischer 344 (F344) rats after intraperitoneal (i.p.) injection of 27-35 mg/kg STZ. Cisplatin (5 mg/kg, i.p.) nephrotoxicity was examined in normoglycemic and diabetic rats after 48 and 96 h. Cisplatin was nephrotoxic within 96 h to normoglycemic animals as indicated by an increased kidney weight, marked elevations in serum BUN levels as well as significant P less than 0.05) decreases in renal cortical slice accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA). Cisplatin failed to depress renal cortical slice accumulation of PAH and TEA in the diabetic rats. Cisplatin was also less effective in increasing BUN levels or kidney weight in diabetic rats. Further studies investigated the impact of glycosuric diuresis and ketone bodies on cisplatin nephrotoxicity. Dextrose diuresis of normoglycemic rats failed to reduce the effect of cisplatin on BUN levels, kidney weight and renal cortical slice uptake of PAH and TEA. Acetone pretreatment of normoglycemic rats also did not reduce cisplatin nephrotoxicity. These results indicate: (1) cisplatin nephrotoxicity is attenuated in the experimental diabetic state, (2) diabetes does not reduce cisplatin nephrotoxicity through glycosuric diuresis and (3) ketone body accumulation does not modulate cisplatin nephrotoxicity. PMID- 2107604 TI - Interaction of thiourea with rat lung protein. AB - Administration of the pulmonary edemagenic agent [14C]Thiourea [( 14C]TU) to adult rats results in heterogeneous binding to lung protein. Indirect evidence suggests that TU may be binding to the amino acid cysteine, possibly via the SH moiety. The nature of the adduct is not known, but appears to involve one major and several minor species. PMID- 2107605 TI - A time course investigation of vitamin A level and lipid composition of the liver endoplasmic reticulum in rats following treatment with congeneric polychlorobiphenyls. AB - The drug metabolizing enzyme activities, the vitamin A content and the fatty acid composition in the endoplasmic reticulum membrane were studied in rat liver after a single injection of the polychlorobiphenyls (PCBs) 3,3',4,4' tetrachlorobiphenyl [(3,4)2Cl] or 2,2',4,4',5,5'-hexachloro-biphenyl [(2,4,5)2Cl], 300 mumol/kg each. The microsomal vitamin A level was markedly lowered 3 days after treatment with (3,4)2Cl, a coplanar type inducer of cytochrome P-450. A marked increase in microsomal AHH and UDPGT activities occurred within 3 days after injection of (3,4)2Cl whereas (2,4,5,)2Cl treatment enhanced APDM activity only. Arachidonic, stearic and linoleic acid microsomal contents were enhanced by the two congeners. (3,4)2Cl caused the proportion of docosahexaenoic acid to decrease. No highly significant correlation was found between the vitamin A content and lipid components in the microsomal membrane. However, the vitamin A level was inversely related to the activities of drug metabolizing enzymes induced by coplanar compounds (cytochrome P-450 towards benzo[a]pyrene and UDP glucuronosyl transferase towards 4-nitrophenol). PMID- 2107606 TI - In vivo determination of valproate binding constants during sole and multi-drug therapy. AB - Valproate (VPA) is present in humans and is largely bound to protein. Only free drug is metabolized, and antiepileptic and toxic effects are probably related to free concentrations. By measuring serial free and total serum VPA levels after routine oral doses, we have determined individual in vivo protein binding parameters for 37 patients after a total of 49 separate drug administrations. Binding site concentrations and dissociation constants were fitted using a nonlinear algorithm. On sole VPA (n = 28) the mean dissociation constant was 91 mumol/L, and the mean concentration of binding sites was 1,176 mumol/L. Evidence suggests a second, nonsaturable binding site. Fraction of unbound VPA ranged from 5.4% at low levels up to 38.7%, rising with increasing total concentration. Concurrent therapy with phenytoin (n = 7) or carbamazepine (n = 8) did not cause displacement of VPA. Changes in free fraction were consistently observed during the interdose interval. The data demonstrate that the binding changes are not a factor in decreased VPA levels during coadministration of other antiepileptic drugs. PMID- 2107607 TI - Fluctuations of unbound and total phenytoin concentrations during the day in epileptic patients on valproic acid comedication. AB - The influence of daily fluctuations in the concentration of valproic acid (VPA) on the unbound and total concentration of phenytoin (PT) was examined in a prospective study. The serum concentrations of 28 patients with epilepsy (group PT + VPA) who were treated with PT and concurrently with VPA and 15 patients (group PT) who were treated with PT but without VPA comedication were determined at 8.00, 11.00, 14.00, 17.00, and in part at 20.00 h. The results show that there are significantly greater fluctuations in the total PT concentration among patients on VPA than those not on VPA. The fluctuations in the total PT concentration during the day correlated with the fluctuations in the VPA concentration. On the other hand, the fluctuations in the concentrations of unbound PT of patients on VPA were comparable with those not on VPA. In the absence of VPA, the diurnal fluctuations of the total PT concentration correlated highly significantly with the fluctuations of the unbound PT concentration. This is not the case in patients on VPA. Our data are a further indication of the smaller significance of the total PT concentration as compared with the unbound PT concentration in the combined treatment of PT and VPA. PMID- 2107608 TI - Lack of acute effect on lidocaine pharmacokinetics from parenteral nutrition. AB - We tested the hypothesis that amino acids in a parenteral nutrition (PN) solution would result in the decreased metabolism of a model compound, lidocaine. One bolus infusion of lidocaine HCl (1 mg/kg) was administered to seven healthy subjects in association with each of three nutrient regimens: (a) a standard PN solution, (b) 10% dextrose water (D10W), and (c) a meal (control) containing similar fluid volume and caloric, protein, and sodium content as the PN solution. Intravenous nutrients were infused consecutively in a random order at 1 L/12 h. Intravenous and control studies were performed 28 days apart. There was no significant difference in the means (+/- SEM) of total body clearance [7.70 +/- 0.70 (PN) versus 6.78 +/- 0.79 (D10W) versus 7.86 +/- 0.93 (control) ml/min kg], half-life [74.0 +/- 12.2 (PN) versus 89.6 +/- 4.35 (D10W) versus 79.2 +/- 7.22 (control) min], volume of distribution [0.82 +/- 0.15 (PN) versus 0.88 +/- 0.13 (D10W) versus 0.78 +/- 0.13 (control) L/kg], and the fraction of unbound lidocaine in the serum [0.34 +/- 0.025 (PN) versus 0.36 +/- 0.019 (D10W) versus 0.33 +/- 0.020 (control)] among the three nutrient regimens. The concentration time course of the active metabolite, N-ethylglycyl-2,6-xylidide, did not differ significantly regardless of the nutritional regimen used. Our study indicates that amino acids used for PN do not have any acute effect on lidocaine pharmacokinetics in healthy subjects. PMID- 2107609 TI - Murine monoclonal antibody MB-2D10 recognizes Rh-related glycoproteins in the human red cell membrane. AB - The human red cell membrane components reacting with monoclonal antibody MB-2D10 were examined by immunoblotting. The antibody bound to a diffusely staining band extending from Mr 30,000 up to the high-molecular-weight region of the gel in normal membranes and in Rhnull U + membranes, but not in Rhnull U - membranes. Treatment of normal red cells with an endoglycosidase F-containing preparation destroyed the epitope recognized by MB-2D10. The reactivity of the antibody with purified preparations of Rh-related glycoproteins D30 polypeptide, D50 polypeptide, R6A32 polypeptide, and R6A45 polypeptide was also examined. Only the purified R6A45 and D50 components reacted with MB-2D10. These results show that MB-2D10 recognizes a carbohydrate-dependent epitope on the R6A45 and D50 group of Rh-related polypeptides. The results also suggest the possibility that the U antigen arises from interaction between glycophorin B and the Rh-related components D50 and R6A45. PMID- 2107610 TI - Flow cytometric studies of the D antigen of various Rh phenotypes with particular reference to Du and Del. AB - Flow cytometric analysis was performed on red cells (RBCs) to compare the antigen activity of various Rh phenotypes, including the rare variants Del and Du (both high-grade and low-grade), whose genotypes were confirmed or presumed by the family study. This appears to be the first report that the Del phenotype is due to the inhibitory effect of Cde. This study also compares the quantity of the D antigen in different phenotypes, whose genotypes comprise the same Du gene (cDuE) transmitted in a family. RBCs were stained by the indirect immunofluorescence method using IgG anti-D purified through a protein-A affinity column. The mean fluorescence intensity obtained for each genotype representing the activity of the D antigen decreased in the following order (percentages show relative fluorescence intensity taking cDE/cDE control as 100% and Cde/cde as 0%): CDe/cDE, 76 percent; CDe/cde, 73 percent; cDE/Cde, 70 percent; cDE/cDuE, 68 percent; CDe/Cde (high-grade Du), 59 percent; cDuE/cde (low-grade Du), 6 percent; and cDuE/Cde (Del), 3 to 4 percent. PMID- 2107611 TI - Phosphorylation of Gi in intact cells. PMID- 2107612 TI - Conformational stability of globular proteins. AB - The conformational stability of ribonuclease T1 has been measured as a function of the variables of most interest to biochemists: temperature, pH, salt concentration, disulfide-bond content and amino acid sequence. The results provide insight into the forces that stabilize globular proteins. PMID- 2107613 TI - Short chain diol metabolism in human disease states. AB - Recent clinical studies have shown the presence of two short chain diols, meso 2,3-butanediol and D/L-2,3-butanediol, and in most cases 1,2-propanediol in either serum or urine collected from humans in several apparently unrelated disease states: congenital propionic and methylmalonic acidemia, premature infants, and alcoholics both in the presence and absence of ethanol. In addition 1,2-propanediol has been shown in patients during prolonged starvation, and in patients with diabetic keto-acidosis. No common defect is known to exist in these metabolic states. Understanding how these compounds are produced in clinically well-defined diseases such as methyl malonic and propionic aciduria, however, may help explain how and why these compounds are produced in alcoholics. PMID- 2107614 TI - Human islet xenograft survival in diabetic rats. A functional and immunohistochemical study. AB - Prolonged survival of human islet xenografts under the kidney capsule of diabetic rats was achieved. Human islet xenograft survival time for the nonimmunosuppressed and single-dose antithymocyte serum-treated rats were 3.7 +/- 0.33 days (mean +/- SE, n = 6) and 4.2 +/- 0.63 (n = 4), respectively. In the recipients given 5 doses of ATS after islet transplantation, the graft survival time was significantly prolonged to 18.2 +/- 1.9 days (n = 6). An intravenous glucose tolerance test was performed on 3 recipients with a functional graft 12 days after xenotransplantation. The mean K rate was 1.44 +/- 0.43 (n = 3) compared with that of 2.1 +/- 0.14 (n = 5) found in normal control rats. Human C peptide was present in the rat recipients following islet transplantation. In addition all 3 recipients showed significant basal human C-peptide values posttransplant and achieved levels of above 2.4 ng/ml during IVGTT. Morphologic and immunohistochemical examination of the islet grafts show that in recipients without immunosuppression or with a single dose of ATS, there was marked degree of fibrosis with little endocrine tissue left in the graft area by day 5. In contrast, the xenograft from recipients treated with 5 doses of ATS still contained well-preserved islet tissue with many insulin and glucagon containing cells on the day of graft removal when blood glucose had returned to the hyperglycemic level. Infiltration of the graft area with lymphoid cells (OX1+, OX8+, and W3/25+) was prominent, but they were not detected within the islets. Staining with monoclonal antibody clone L243 did not detect any expression of human class II antigen on the human pancreatic endocrine cells undergoing rejection by the host. This study has shown that with adequate immunosuppression human islet xenograft can normalize the blood glucose with prolonged survival time in diabetic rat recipients. The discordant xenotransplantation model used in this study would be useful for future xenotransplantation studies. PMID- 2107615 TI - Hyperbaric oxygen effect on active Na+ transport across isolated toad skin. AB - The effect of hyperbaric oxygen (HBO) on Na+ transport across the isolated toad (Bufo marinus) skin was studied by measuring the transepithelial short-circuit current (ISC) and resistance (R) at 5, 8, and 10 ATA PO2 and 15 ATA normoxia during steady state conditions. The imposition of 5, 8, and 10 ATA PO2 for 2 h resulted in 45, 52, and 85% decrease in ISC, respectively. This decrease in ISC was always accompanied by an increase in R. When amiloride (10(-4) M) was added to the bathing medium, ISC decreased to zero within 15 min regardless of the PO2 level, indicating that the HBO-induced decrease in ISC is caused by an inhibition of amiloride-sensitive Na+ transport. Addition of both superoxide dismutase (SOD) and catalase to the medium bathing both sides of the skin markedly attenuated the HBO effect on ISC and R. Applying HBO to the serosal or mucosal surface independently produced similar effects on ISC. However, the presence of antioxidant enzymes (SOD and catalase) with 10 ATA PO2 prevented the toxic HBO effect only from the serosal side; no protection by these antioxidant enzymes was observed from the mucosal side. These findings are consistent with a view that free radicals are involved in the HBO-induced inhibition of ISC. However, further studies involving the site(s) of radical generation as well as site(s) of toxic action are needed to understand the cellular and molecular mechanism of HBO toxicity. PMID- 2107616 TI - Symptomatology during hypoxic exposure to flame-retardant chamber atmospheres. AB - Hypoxia was studied in 12 men during 63-h exposures to 17 and 13% O2, with the subjects serving as their own controls by repeating the measurements in 21% O2. All test atmospheres were contaminated with 0.9% CO2 to simulate the condition of living aboard submarines. The mean SaO2's were 97-98% in all conditions of 21% O2, 96% in 17% O2 (n.s.), and 92% in 13% O2 (P less than 0.05). The blood concentrations of 2,3-diphosphoglycerate were elevated in 13 and 17% O2 (P less than 0.05). Seventeen percent O2 did not cause significant symptoms of environmental stress; however, 13% O2 caused symptoms of acute mountain sickness in 5 of 12 men. In the last 7 h of exposure to 17% O2, reduction of the barometric pressure to 576 Torr reduced the ambient PO2 to 98 Torr (similar to the PO2 of 13% O2 at normobaric pressure). This induced symptoms of acute mountain sickness in 3 of 11 men. All symptomatology and physiologic changes were reversed during recovery in 21% O2. Monitoring devices indicated the presence of volatile organic contaminants at a mean concentration of 6.1 ppm in the chamber atmosphere. Combustion tests in the occupied chamber showed that flame propagation was retarded by lowering the O2 concentration from 21 to 13-17%. We conclude that men can live comfortably in a normobaric, flame-retardant atmosphere consisting of 17% O2-0.9% CO2-6.1 ppm volatile organic compounds balance N2. PMID- 2107617 TI - Bubble formation properties of hydrophobic particles in water and cells of Tetrahymena. AB - It is generally assumed that hydrophobic surfaces play a role in bubble formation in vivo, but no tests of this assumption seem to exist. Model systems for both in vitro and in vivo study of the bubble nucleation properties of hydrophobic surfaces were developed. First, aqueous suspensions of particles were exposed to gas supersaturations, and the numbers of bubbles that formed were determined. Although the supersaturation thresholds for spontaneous bubble nucleation in pure water exceeds 175 atmospheres gas tension, gas tensions of only a few atmospheres caused the profuse formation of bubbles with the most effective particles. Some or most of this latter effect seemed to be caused by gas trapped in irregularities on the particles. Second, particles that were especially effective bubble promoters were added to suspensions of ciliates. Upon their ingestion, all of the particles lost their ability to induce bubble formation in the cells with supersaturations equal to or exceeding the threshold for spontaneous nucleation in water. These results indicate that intracellular bubble formation may not occur readily in vivo. PMID- 2107618 TI - Microwave: practical cost-effective method for sterilizing urinary catheters in the home. AB - We used a standard microwave oven to sterilize red rubber catheters used for intermittent self-catheterization. Catheters were incubated for sixty minutes in a suspension of microorganisms isolated from the urine of patients with urinary tract infections. For each trial, 6 catheters were removed from their respective suspensions, placed in separate plastic freezer bags, distributed evenly in a microwave oven (avoiding cold spots), and microwaved simultaneously for twelve minutes. A control catheter was not microwaved. Two strains of each microorganism were tested. The urinary isolates were Escherichia coli, Klebsiella sp., Proteus sp., Enterobacter sp., Pseudomonas sp., Streptococcus sp., Staphylococcus sp., and Candida sp. In each experiment, all 6 catheters were sterilized. Repeat sterilization in the microwave oven did not affect the integrity of the catheters or the plastic bags. A water heat sink of constant volume was employed. A home microwave oven may be used as a method to sterilize red rubber catheters for reuse with a recommended time of twelve minutes at full power. This technique makes aseptic intermittent self-catheterization a practical possibility. PMID- 2107619 TI - The effects of bovine tick resistance on the susceptibility of Hyalomma anatolicum anatolicum to infection with Theileria annulata (Ankara). AB - Two Bos taurus calves were made resistant to tick infestation by exposing them to approximately 500 rabbit-reared nymphs of Hyalomma anatolicum anatolicum twice at a 2-week interval. These two calves, together with a tick-susceptible control calf, were inoculated with a stabilate of Theileria annulata (Ankara). Patent infection resulted in all three calves. Seven-hundred and fifty gerbil-reared nymphs were then applied on each of these calves as well as another tick susceptible calf that was Theileria free. This infestation was carried out on Day 8 post-inoculation. Ticks that dropped on Day 13 post-inoculation were examined to note the development of T. annulata in them and the histological changes that occurred in the gut and salivary glands. During the second phase of feeding, the gut epithelia of the ticks from the tick-resistant calves were less active. There were no notable differences in the characteristics of the developmental stages of T. annulata between the ticks from the tick-resistant calves and those from the susceptible calf. However, ticks from one calf that acquired a higher level of tick resistance were significantly less susceptible to infection by T. annulata. Bovine tick resistance therefore compromises the vector capacity of H. a. anatolicum and this may be of epidemiological significance in the endemic areas of tropical theileriosis. PMID- 2107620 TI - Evidence that Cache Valley virus induces congenital malformations in sheep. AB - An outbreak of congenital abnormalities occurred in sheep at San Angelo, Texas, between December 1986 and February 1987. Of 360 lambs born, 19.2% had arthrogryposis or other musculo-skeletal problems and hydranencephaly (AGH), and the total neonatal loss was 25.6%. In 1987, all ewes that were tested with AGH lambs had antibody to Cache Valley virus (CVV), whereas 62% of the ewes with normal lambs had CVV-specific antibody. Pre-colostral serum samples from AGH lambs had neutralizing antibody to CVV. An increase in prevalence of CVV-specific antibody, from 5% during the spring of 1986 to 63.4% during the winter of 1987, occurred during a time that included the gestation of these affected lambs, as well as a period of increased rainfall. The isolation of a CVV-related strain from a sentinel sheep in October 1987 confirmed the continued presence of this virus in the pasture where this outbreak occurred and provided a recent field strain for future studies. PMID- 2107621 TI - Characterization of monoclonal antibodies against ovine Sarcocystis spp. antigens by immunoblotting and immuno-electron microscopy. AB - Six monoclonal antibodies were raised in mice against purified cytozoite extracts of Sarcocystis gigantea and S. tenella from sheep. Each monoclonal antibody was evaluated for specificity by enzyme immunoassay, immunoblotting and immuno electron microscopy using homologous and heterologous antigenic preparations. All six monoclonal antibodies exhibited good species-specificity when reacted against crude soluble cystozoite antigens in enzyme immunoassays. However, only two monoclonal antibodies (IgM and IgG2a) exhibited reactivity in Western blots against specific protein bands. Both reacted against S. gigantea antigens of 100,000, 43,000 and 39,000 molecular weight. Neither monoclonal antibody reacted against the heterologous species S. tenella. Ultrastructural studies performed with colloidal-gold conjugated antisera revealed that both monoclonal antibodies reacted against antigens located around micronemes and amylopectin granules in S. gigantea cystozoites. Another monoclonal antibody (IgGI) reacted only against microneme determinants in S. tenella cystozoites. In contrast, polyclonal sheep and rabbit immune sera cross-reacted against a wide range of cystozoite antigens. PMID- 2107622 TI - Recovery of bovine oocytes from small vesicular follicles for in vitro maturation and fertilization. AB - Five dairy and four beef breed, mature cows were used as oocyte donors to develop a system of multiple recovery of oocytes for in vitro maturation and fertilization. The animals were alternately treated with either 20 mg of follicle stimulating hormone (FSH) in four equal intramuscular injections or saline at 12 h intervals starting between days 9 and 13 of the oestrous cycle, and the procedure was repeated at three-week intervals for up to four collections. Eighteen collections resulted in the recovery of 124 oocytes from 181 follicles (69%). No serious side-effects were observed. Recovery was equally successful in both breeds and was not reduced in repeat attempts upon the same animal. Treatment with FSH only marginally increased the recovery rate (p less than 0.07) and did not affect the number of follicles aspirated (p greater than 0.05), which varied significantly (p less than 0.05) between cows. From 110 oocytes matured and fertilized in vitro, 70 embryos were recovered after culture in the rabbit oviduct or with trophoblastic vesicles in vitro, of which 30 had cleaved and 5 had progressed to an advanced stage of development. Hormone treatment did not affect zygote development (p greater than 0.05). Four non-surgical transfers of embryos obtained in these studies have resulted in two pregnancies determined ultrasonographically and the birth of a heifer calf. This suggests that the procedure for multiple oocyte recovery is safe and that it can be used successfully for obtaining oocytes for in vitro maturation and fertilization. PMID- 2107623 TI - Degenerative change of adipose tissue; the so-called membranous lipodystrophy. PMID- 2107624 TI - Cytoskeletal characteristics of myofibroblasts in benign neoplastic and reactive fibroblastic lesions. AB - The characteristics of the cytoskeleton of myofibroblasts were examined immunohistochemically in 10 extra-abdominal desmoid tumours, 3 palmar and 2 plantar fibromatoses and 5 nodular fasciitis; in the cultured cells of one desmoid tumour, and also ultrastructurally in 3 desmoid tumours. Polyclonal anti desmin antibody reacted with the cells in 7 extra-abdominal desmoid tumours, 1 palmar fibromatosis, 1 plantar fibromatosis and 3 nodular fasciitis. Monoclonal antidesmin antibody reacted with cells in only 2 desmoid tumours. Desmin-positive spindle cells were scattered throughout these lesions. There were no marked ultrastructural differences between desmin-positive and desmin-negative desmoids. All specimens except one specimen of nodular fasciitis showed immunoreactivity for alpha-smooth muscle actin and vimentin. Muscle actin-positive cells were observed in all specimens. Cultured cells gave positive reactions with polyclonal desmin antibody as well as to vimentin antibodies and two preparations of actin antibodies, whereas the original tumour did not react with desmin antibody. The present studies suggested that the cytoskeleton of some myofibroblasts in both neoplastic and reactive lesions resembles that of smooth muscle cells. PMID- 2107625 TI - Scanning electron microscopic evidence for neural differentiation in Ewing's sarcoma cell lines. AB - A number of recent studies have suggested a relationship between Ewing's sarcoma (ES) and other small round cell tumours of childhood such as peripheral neuroepithelioma (PN). We report scanning electron microscopic studies on the character of induced neural differentiation in ES, neuroblastoma, PN, osteosarcoma and colon carcinoma. We found evidence of neural differentiation in both neural lines and in one of two Ewing's lines before treatment. After differentiation, both Ewing's and neural lines developed neuritic processes with varicosities and little arborization, except for the initially undifferentiated Ewing's line (A4573) which displayed extensive lateral sprouting from neuritic processes after differentiation. Neither treated nor untreated osteosarcoma or colon carcinoma displayed any evidence of neural differentiation. Further, neuroblastoma cells are easily distinguished from ES and PN by virtue of their single, unbranched neurites and lack of lateral sprouting or filopodia. These results provide further evidence for the neural character and close relationship between ES and PN. PMID- 2107626 TI - Colonic mucosal changes in nude mice associated with orthotopic xenografts of human colon cancer cells. AB - We used the nude mouse tumour xenograft model to study the pathogenesis of mucosa alterations in the large bowel surrounding a carcinoma. In mouse colonic mucosa overlying HT-29 colonic carcinoma xenografts in the caecum, the crypts were elongated in comparison with those in distant mucosa and also frequently showed a shift towards sialomucin production. These features, which are comparable with socalled transitional mucosa (TM) in man, were absent in control animals inoculated with Indian Ink instead of HT-29 cells. Although the localization of the proliferative cell compartment in mouse colonic mucosa overlying HT-29 xenografts appeared to be confined to the lower half of the crypt as in normal mucosa, the relative length of the DNA synthesizing cell compartment along the crypts was slightly elongated. These data strongly suggest that TM should be regarded as a secondary phenomenon rather than a premalignant change in large intestinal epithelium and that higher proliferative activity of epithelial cells contributes little to the elongation of crypts in TM. PMID- 2107627 TI - Immunohistochemical study of the abnormal cells in Langerhans cell histiocytosis (histiocytosis x). AB - The immunophenotypic properties of the abnormal cells in routine specimens from 16 cases of Langerhans cell histiocytosis (LCH) were examined. In five cases, cryostat sections were also available. The abnormal cells expressed a similar phenotype and were positive for HLA-DR, S-100 protein, peanut agglutinin (PNA), CD1a, CD4 and several macrophage-associated markers, including CD11c, CDw32 and CD68 (the latter detectable in routine sections with antibody KP1). Staining with CD14, CD35 (C3b receptor), and CD11b (C3bi receptor) was negative with the exception of one of the cases in which a proportion of the cells showed faint positivity with CD11b. Staining for pan-T-cell (CD2, CD3, CD5) and pan-B-cell (CD19, CD22) antigens was negative in all lesions. It is concluded that LCH expresses a characteristic phenotype with some heterogeneity with regard to macrophage markers and that immunohistochemical methods in cryostat sections and routine specimens form a useful supplement to other techniques for the diagnosis of this condition. PMID- 2107628 TI - Augmented enkephalin-immunoreactivity in adrenaline-producing phaeochromocytomas. AB - Immunohistochemical studies for methionine- and leucine-enkephalin were performed on 26 phaeochromocytomas to elucidate the patho-physiological roles of enkephalins. Positive reactions were seen in all phaeochromocytomas with varying intensities. The location of methionine- and leucine-enkephalin agreed fairly well with each other. Stronger immunostaining was obtained in phaeochromocytomas secreting both adrenalin and noradrenaline than in those secreting predominantly noradrenaline. Paroxysmal hypertension was frequently observed in patients with adrenalin-secreting phaeochromocytomas, especially those with marked enkephalin positivity. Urinary excretion of metanephrine was significantly correlated with enkephalin positivity. These findings show that all phaeochromocytomas retain the ability to produce enkephalins of the adreno-medullary or extra-medullary chromaffin tissues from which they derive. Augmented enkephalin-immunoreactivity in adrenalin-producing phaeochromocytomas may be interpreted as reflecting a close association of enkephalins with adrenalin under physiological conditions. PMID- 2107629 TI - Deposition of lipopigment--a new feature of human splenic sinus endothelium (SSE). Ultrastructural and histochemical study. AB - Lipopigment (LP) deposition was studied in a series of 36 control and 79 pathological spleens. In the control group the LP deposition in SSE was rudimentary and did not display age-dependence. A varying degree of lysosomal and cytoplasmic siderosis was a frequent finding in haemolytic anemia without any significant LP induction. In the acquired secondary storage syndrome and in some inherited lysosomal enzymopathies, the amount of LP in splenic sinus endothelium (SSE) was significantly increased and in some instances its deposition reached very high values. As deposition was not accompanied by any detectable lysosomal lipid storage phenomenon in pulpar histiocytes, the pigmentogenesis is thought to be by a process resembling that for lipofuscin. In ceroid-lipofuscinosis group the SSE affection was of low degree, as seen in other viscera. The LP deposition seems thus to be a prominent, albeit variable feature of human SSE lysosomal pathology and may represent a monotonous response to various stimuli connected with increased demands on the SSE lysosomal system. Only in some lysosomal enzymopathies, typically in sphingomyelinase deficiency was SSE LP deposited progressively and concurrently with the stored lipid. LP deposition was accompanied by an increase in lysosomal enzyme activities but lacked the alkaline phosphatase induction in SSE described in lipid and mucopolysaccharide storage diseases. This and several other features which are reviewed clearly distinguish SSE from the pulpar histiocytes with which they have been often identified. PMID- 2107630 TI - Haemopoiesis in human fetal and embryonic liver. Immunohistochemical determination in B5-fixed paraffin-embedded tissues. AB - Paraffin embedded tissue reactive monoclonal antibodies were used to study human embryonal and fetal haemopoiesis, combining optimal morphology with immunohistological determination of haemopoietic cell subtypes and their microenvironment. Seven embryonal and twelve fetal liver specimens were studied, having been fixed in B5-fixative and embedded in paraffin. The different haemopoietic lineages each showed their own immunophenotype and distribution; intercellular and microenvironmental relationships were easily determined. Erythroid cells are reactive with VIE-G4, LN1, and MT1, sometimes partly surrounding a central macrophage. Myelomonocytic cells react with LCA, MT1, MB3, LN2, and anti-lysozyme, and from 14 weeks onwards with LN3. Lymphoid cells show LCA, MT1, MT2, MB1, MB2, MB3, and LN2 reactivity. In a few cases some scarce My10+ early progenitor cells were seen. An important finding is the extensive MT1 reactivity distributed over all haemopoietic lineages, and the demonstration of immature haemopoietic blast cells exclusively expressing the MT1 antigen. Further studies employing MT1 are necessary to delineate the extent of the distribution and the possible function of the antigen. Use of the MT1 mAb may contribute to the elucidation of the exact nature of the haemopoietic blast cells and their place in haemopoietic development. PMID- 2107631 TI - The spleen in osteomyelofibrosis. A morphological and immunohistochemical study of 30 cases. AB - 30 spleens from patients with biopsy proven primary osteomyelofibrosis were studied by histological and immunohistochemical methods. The presence of trilinear haematopoiesis along the splenic circulatory pathway supports the theory that the spleen acquires haematopoietic precursor cells by filtration of the peripheral blood. In addition, impairment of intrasplenic circulation with subsequent red pulp congestion, pulp cord fibrosis and haemophagocytosis is of importance for the pathogenesis of both marked splenic haematopoiesis and complications due to hypersplenism. PMID- 2107632 TI - Adrenomedullary hyperplasia and phaeochromocytoma. DNA cytophotometric findings in 47 cases. AB - Fifty adrenalectomy specimens containing normal (n = 3), hyperplastic (n = 4) or neoplastic (n = 43) medullary tissue were subjected to quantitative cytophotometric measurements of DNA content. Differing evaluation schemes were applied for interpretation of DNA distribution patterns. Of the 43 phaeochromocytomas (PCC), 16 were inherited as part of the syndrome of multiple endocrine neoplasia type 2a (MEN 2a). Five of 27 sporadic PCCs followed a malignant course. Three benign and three malignant PCCs lacked endocrine activity. In normal medulla and in adrenomedullary hyperplasia, diploid or euploid DNA distributions were found. In contrast, 87% (33/38) of the benign and all 5 malignant PCCs exhibited non-diploid or aneuploid DNA histograms. No differences in DNA content existed between functioning and non-functioning PCCs or between sporadic and hereditary tumours. In this study, in contrast to earlier communications, DNA cytophotometry did not discriminate between benign and malignant adrenomedullary tumours. In addition, as opposed to the findings in a variety of other endocrine tumours, DNA measurements did not appear to be a useful tool to assess the prognosis of an individual malignant PCC. PMID- 2107633 TI - Nerve fibre proliferation in interstitial cystitis. AB - The aetiology of pain in interstitial cystitis is not understood, although it has been reported to be due to release of mediators from mast cell granules. Cystolysis and intravesical instillation of dimethyl sulphoxide have been shown to relieve pain in this condition. We have studied the nerve population within the bladder wall using immunohistochemical stains for protein gene product 9.5. A group of 18 cases of chronic interstitial cystitis and 12 controls; neuropathic bladder (n = 1), chronic bacterial cystitis (n = 3), systemic lupus erythematosus cystitis (n = 2) and normals (n = 6), were investigated. There were significantly more nerve fibres within the sub-urothelial and detrusor muscle layers in chronic interstitial cystitis than there were in normals. Patients with chronic cystitis of other aetiology did not have a significant increase in nerve fibre density within the bladder wall suggesting a specific association between nerve fibre proliferation and interstitial cystitis. Cystolysis is shown to deplete selectively the submucosal nerve plexuses without altering the nerve density within detrusor muscle. This finding explains the desensitisation of the bladder without impairment of detrusor function after this procedure. PMID- 2107634 TI - Primary lipid cardiomyopathy. AB - In this communication, we describe an isolated, apparently congenital cardiomyopathy (CMP) characterized by the accumulation of stainable lipid in mitochondria of cardiomyocytes. This lesion, which we term primary lipid cardiomyopathy, has not been reported so far. The structural alteration was associated with progressive heart failure, leading to death at the age of 3 years, and with massive hypertrophy of myocardium. Lipid storage in heart muscle cells resulted in an impressive yellow to orange color of the myocardium. We suggest that this type of primary CMP may represent a new member within the group of mitochondrial CMPs. Possible pathogenic mechanisms are discussed. PMID- 2107635 TI - Crusted scabies in a patient with the acquired immunodeficiency syndrome. AB - A case of crusted (Norwegian) scabies in a patient with the acquired immunodeficiency syndrome (AIDS) is described and seven previous reports of this association are reviewed. Injury to epidermal Langerhans' cells by the human immunodeficiency virus or cytotoxic cells may explain the appearance of this unusual form of scabies in patients with AIDS. PMID- 2107636 TI - High molecular weight aggregate content of heated and unheated factor VIII products determined by fast-protein liquid chromatography. AB - The molecular-weight distribution of proteins in factor VIII concentrates has been analysed by fast-protein liquid chromatography. The proportion of high molecular-weight (HMW) aggregates in one product increased on freeze-drying and heating, with fibrinogen and fibronectin being the main protein components of the HMW peak. In all other concentrates, the HMW peak was less than or equal to 5% of the total protein content and there were no differences in HMW content according to purity or method of viral inactivation. PMID- 2107637 TI - [Defects in the prostaglandin system. IX. Lipoxygenase defect of thrombocytes in a patient with polycythemia vera]. AB - Patients with the myeloproliferative syndrome (MPS) often show morphological and functional platelet abnormalities and an increased incidence of lowered cyclooxygenase- and/or lipoxygenase activity. We present the case history of a 68 year-old male patient with polycythaemia vera in whom an absolute absence of platelet lipoxygenase activity has been detected for the first time in the literature. PMID- 2107638 TI - [Effectiveness and tolerance of disodium cromoglycate capsules in pellet form]. AB - The efficacy of, and tolerance to lactose-free sodium cromoglycate capsules was investigated in a multicentre trial. Data of 154 patients with asthma treated at 41 centres were evaluated over an observation period of 5 weeks. During treatment there was a significant reduction in the required dosage of concomitant medication, a marked improvement with regard to the severity of symptoms and a significant increase in peak flow rates. Assessment of treatment was "good" or "very good" in 86% of patients. Mild side effects such as cough or throat irritation were seen in only 2.6% of patients. PMID- 2107639 TI - Stability of famotidine in a 3-in-1 total nutrient admixture. AB - The stability of famotidine in a 3-in-1 total nutrient admixture stored at room temperature (24 degrees C) was evaluated over 24 hours. Famotidine injection was diluted to a theoretical concentration of 20 mg/L in a total nutrient admixture containing 5% amino acid injection, 25% dextrose injection, and 2.25% intravenous fat emulsion. Admixtures were prepared in 2-L ethylene-vinyl acetate bags using conventional techniques and stored at room temperature. At 0, 4, 8, 12, and 24 hours, the admixtures were visually inspected for color change, creaming, or phase separation, and samples were obtained for assay with a stability-indicating method of HPLC, using samples obtained at time zero as controls. Two-way analysis of variance was used for data evaluation. There was no evidence of color change, creaming, or phase separation before quantitative analysis was performed, nor was there significant change in observed famotidine concentration over 24 hours. Based upon our data, famotidine intravenous solution 20 mg/L in the solution tested is stable at room temperature for 24 hours. PMID- 2107640 TI - Valproic acid in bipolar disorder. PMID- 2107641 TI - Clinical issues regarding the use of total nutrient admixtures. AB - The introduction of total nutrient admixtures (TNAs) has offered several clinical advantages. Substituting a portion of the daily dextrose calories with lipids may reduce the incidence of carbohydrate-associated complications (e.g., disturbances in glucose control and immune function). In addition, providing intravenous lipids continuously over 24 hours as a TNA appears to be better utilized by the liver and less likely to interfere with reticuloendothelial system function when compared with conventionally administered, discontinuous lipid infusions. If the peripheral vein is used as a route for parenteral nutrition, the addition of fat to the admixture provides the advantage of enhancing caloric density, while contributing significantly less tonicity than dextrose. Certain pharmaceutical and microbiological issues need to be considered to ensure the intravenous administration of a safe and homogenous dispersion. Attention to established guidelines provided by the lipid manufacturers, as well as careful extrapolation of TNA stability data, will avert the dangers associated with infusion of coalesced lipid particles. This article reviews the evidence supporting the use of lipids as daily caloric sources, with particular emphasis on the role of the total nutrient admixtures as the primary vehicle for administration. PMID- 2107642 TI - Aminophylline via TPN. PMID- 2107643 TI - [The acute phase reaction and its mediators. II: Alpha tumor necrosis factor and interleukin 6]. AB - Acute phase reaction is a fast, unspecific and highly complex reaction of the animal organism to injury and infection. Main symptoms and metabolic changes are fever, leucocytosis, dramatic rearrangement of plasma protein synthesis in the liver and of the protein synthesis in several other organs. The identification of the liver as main source of plasma proteins lead to the assumption, that the host reaction to the injury, and not the injury itself, is responsible for those changes. Now today, it has been demonstrated, that at least three monokines, mainly produced by cells of the monocyte-macrophage lineage, namely interleukin 1, tumor necrosis factor-alpha and interleukin-6 can mediate the acute phase response. As they can act locally as well as at distant sites in nanomolar concentrations the monokines are considered to be new hormones. Whether other newly recognized macrophage products are also involved in acute phase response has to be clarified. PMID- 2107644 TI - [Pathogenesis of thrombosis development in parenteral nutrition]. PMID- 2107645 TI - [Successful treatment of flecainide (Tambocor) poisoning--effect of hemodialysis/hemoperfusion?]. AB - After suicidal ingestion of 3 g flecainide a 34-year-old woman showed somnolence, cerebral convulsion, disturbances of atrioventricular and intraventricular conduction and ventricular asystole. The maximum flecainide plasma level was 4900 ng/ml; this level is extremely high and exceeds the maximum therapeutic level by five times. After initial cardiopulmonary resuscitation and stabilization by intensive care treatment we performed a combined hemodialysis/hemoperfusion therapy (with activated charcoal). This procedure led to a rapid decrease of flecainide plasma levels and simultaneous improvement of ECG-alterations. The initial decrease in flecainide plasma levels during extracorporeal elimination occurred much quicker (4.5-8.5 h plasma halflife) than the spontaneous decrease rate of flecainide in humans (12-20 h plasma half-life). We conclude that, perhaps, hemodialysis/hemoperfusion therapy is an efficient method for decreasing toxic plasma levels of flecainide and for improvement of the clinical course of this intoxication. PMID- 2107646 TI - Preparation of a diphtheria toxin-pullulan conjugate that elicits good IgG antibody production with poor IgE synthesis. AB - Diphtheria toxin is detoxified through conjugation with pullulan. The toxin pullulan conjugate is easily purified by DEAE-Sephacel chromatography. The conjugate forms a transparent 'clear line' with anti-toxin antibodies on agarose plate, which offers a good indicator of conjugate formation. The toxin-pullulan conjugate induces both IgG1 and IgG2b antibody production with diminished IgE response, while the alum-precipitated conventional toxoid causes mainly increases in IgE as well as IgG1 antibody formation. The anti-toxin HA titre (IgG antibody) induced by the toxin-pullulan conjugate parallels the neutralizing activity of the immune-sera. These results suggest that the conjugation of toxin to pullulan is a very powerful method by which to develop a vaccine that induces neutralizing antibody with diminished IgE antibody synthesis. PMID- 2107647 TI - Further analysis on the structural proteins of infectious pancreatic necrosis virus. AB - The structural proteins of infectious pancreatic necrosis virus (IPNV) have been analyzed. Two-dimensional gel electrophoresis showed that IPNV proteins are slightly acidic with apparent pIs ranging from 5.8 to 6.6. To identify the IPNV surface-located proteins, purified virus was labelled either with fluorescein isothiocyanate (FITC) or with Na 125I. After analysis by SDS-PAGE, only the major viral protein, VP2, was labelled by either procedure. The accessibility of VP2 to these reagents suggests that this protein is externally located. In addition, using Concanavalin A conjugated with FITC and IPNV labelling with 3H-mannose, evidence is present that VP2 contains carbohydrate residues. PMID- 2107648 TI - Comparative study on cytochrome P-450 of yeasts using specific antibodies to cytochromes P-450alk and P-450(14DM). AB - The occurrence of cytochrome P-450(14DM) (lanosterol 14 alpha-demethylase) and cytochrome P-450alk (long-chain alkane terminal hydroxylase) in various yeast strains was determined with immunological procedures. Cytochrome P-450(14DM), which is constitutive or housekeeping enzyme playing an essential role in ergosterol biogenesis, was found in all yeast strains so far tested. Cytochromes P-450(14DM) from different species of yeast were immunologically different, although they may have had a few common antigenic sites. In contrast, cytochrome P-450alk was detected only in the alkane-assimilating yeasts. PMID- 2107649 TI - [Clinical and endocrinologic aspects of treatment with pure FSH. A report of experiences]. AB - Ovarian stimulation with pure urinary FSH (Fertinorm, Serono Freiburg, FRG) shows therapeutic efficacy in patients with chronic clomiphene-resistant anovulation and elevated androgen levels. In case of unsatisfactory ovarian response the rate of success can be improved by adding HMG. 20 patients were stimulated for a total of 36 cycles. Cycle monitoring was performed by transbdominal ultrasound and cervical mucus evaluation. Hormone determination (E2, LH, FSH, prolactin, testosterone, DHEAS) was carried out retrospectively. In 17 cycles HMG was added because of insufficient follicle maturation. Upon achieving a dominant follicle with a diameter of more than 1.6 cm (25 cycles, 14 of those with FSH stimulation only) HCG was applied for induction of ovulation. In 22 cycles ovulation occurred. 7 of those revealed sings of luteal phase deficiency. In anovulatory cycles (n = 3) there was a discrepancy between sonography and E2-levels. Premature increase in LH, partly with subsequent luteinization of follicles was observed in 7 of all 36 cycles (19.4%), 2 of those under sole FSH-stimulation. The number of dominant follicles on the day of HCG-application was 1.40 +/- 1.06 (n = 15) in cycles with FSH alone and 2.09 +/- 1.76 (n = 11) in cycles with additional HMG. Hyperstimulation (more than 4 leading follicles) was induced in 9 cycles (5 cycles with FSH only). In 7 (4) cases HCG had to be cancelled. Polyfollicular ovarian reaction and premature increase in LH preferentially occurred in cycles with high basel levels of LH and elevated LH/FSH-ratio. PMID- 2107650 TI - Pituitary repetitive stimulation with GnRH/TRH in women treated with three different oral steroid contraceptives. AB - Twelve untreated cycling women and 45 women using oral contraceptives were challenged iv with 50 micrograms of GnRH and 100 micrograms of TRH at 0, 90 and 180 min. The LH responses after the second and third pulses of GnRH/TRH were diminished in women treated with 30 micrograms of ethinylestradiol and levonorgestrel as compared with the control group, whereas the responses were severely blunted after each dose of GnRH/TRH in women treated with 50 micrograms of ethinylestradiol and levonorgestrel or lynestrenol as compared with both the control group and the women treated with 30 micrograms of ethinylestradiol and levonorgestrel. The FSH responses to GnRH/TRH in women treated with 30 micrograms of ethinylestradiol and levonorgestrel were similar to those in the control group, whereas there were reductions in the responses obtained in women treated with 50 micrograms of ehinylestradiol and progestin as compared with both the control group and the women under 30 micrograms of ethinylestradiol and levonorgestrel. In women treated with 30 micrograms of ethinylestradiol and levonorgestrel, the PRL peaks after the second and third pulses were higher than the first, and higher than the values obtained in the remaining three groups. PMID- 2107651 TI - Effects of androgens on bioactivity and immunoreactivity of pituitary FSH in GnRH antagonist-treated male rats. AB - The effects of androgens on the bioactivity and molecular composition of pituitary FSH were examined in intact and GnRH antagonist-suppressed male rats. Eight groups of adult Sprague-Dawley rats were subjected to the following treatments: antagonist (75 micrograms/day by osmotic minipumps; sc), testosterone filled Silastic implants (3 X 5 cm, sc), dihydrotestosterone-filled Silastic implants (3 X 5 cm, sc), E2 benzoate (15 micrograms/day, sc), and combined administration of antagonist with either steroid for 3 weeks. At the end of the treatment period, pituitaries were dissected out and homogenised. FSH content was determined in the pituitary extracts by an in vitro bioassay and a radioimmunoassay. Individual pituitary extracts from rats treated with vehicle, testosterone and testosterone + antagonist were subjected to isoelectric-focusing on sucrose density gradients performed in the pH range from 3.5 to 7.0. Individual isoelectric-focusing fractions (100-120) were analysed for bioactive and immunoreactive FSH. Treatment with antagonist, E2 or antagonist + E2 caused a significant decrease in pituitary FSH, whereas testosterone and dihydrotestosterone alone or in combination with antagonist prevented the decrease in pituitary FSH. The effects of all treatments on both bioactive and immunoreactive FSH were similar. Testosterone treatment not only maintained FSH synthesis but also altered the molecular composition of pituitary FSH. Following treatment with testosterone there was a shift of maximal FSH bioactivity to the more acidic pH range. On the other hand, less bioactivity was recovered than corresponding immunoreactivity in the higher pH region, resulting in significantly reduced ratios of bioactivity to immunoreactivity of FSH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107652 TI - Interleukin 6 possibly induced by interleukin 1 beta in the pituitary gland stimulates the release of gonadotropins and prolactin. AB - The abilities of recombinant human interleukin 1 (IL-1) and IL-6 to induce release of FSH, LH and PRL from rat pituitary cells in vitro were examined. IL-1 and IL-6 induced significant releases of FSH, LH and PRL within 3 h. The extents of release of these compounds induced by IL-1 and IL-6 were similar to those induced by GnRH and TRH. Rat anterior pituitary cells released IL-6 spontaneously, and its release was enhanced by IL-1 beta. This effect of IL-1 beta was inhibited significantly by a rabbit anti-IL-1 beta antiserum. These findings suggest that IL-1 induced the release of IL-6 from rat pituitary, and that the released IL-6 stimulated the secretions of FSH, LH and PRL. PMID- 2107653 TI - Acute effects of cortisone acetate on growth hormone response to growth hormone releasing hormone in normal adult subjects. AB - Glucocorticoids have been shown to inhibit GH secretion in normal man when administered in large amounts for several days. The aim of our study was 1. to investigate the acute effects of a single dose of glucocorticoids on GH secretion in normal man; 2. to look at the relationship between the increase in serum cortisol concentration and GH response to the stimuli. Six healthy volunteers received on three occasions in random order an iv injection of GHRH (1-29) NH2, 100 micrograms, alone or 60 min after oral administration of either 25 or 50 mg of cortisone acetate. Mean stimulated GH levels, GH peak and integrated GH concentration were significantly lower after GHRH plus cortisone 25 mg than after GHRH alone. Mean GH levels at 15 and 30 min after GHRH injection and the peak GH level showed a further decrease after GHRH plus cortisone 50 mg. We conclude that acute administration of pharmacological doses of glucocorticoids is able to inhibit GH response to GHRH, probably through enhancement of endogenous somatostatin release. Moreover, this pharmacological effect of glucocorticoids seems to be dose-dependent and thus directly related to serum cortisol concentrations. PMID- 2107654 TI - Effects of a dopamine antagonist (metoclopramide) on the release of LH, FSH, TSH and PRL in normal women throughout the menstrual cycle. AB - To obtain further insight into the role of endogenous dopamine on the adenohypophyseal hormones secretion in normal women, responses of the adenohypophyseal hormones to a dopamine antagonist, metoclopramide, were evaluated in 7 normal women during the early follicular, late follicular and mid luteal phases of the menstrual cycle. PRL increments following metoclopramide were similar in all phases. During the early and late follicular phases, metoclopramide induced no significant change in circulating LH levels. However, a significant rise in serum LH was observed following metoclopramide during the mid luteal phase. No significant changes in serum FSH levels were observed after metoclopramide during any of the 3 phases of the cycle. Following metoclopramide, serum TSH levels significantly rose in all phases. TSH increments following metoclopramide were significantly lower in the mid-luteal phase than in the early follicular phase. These results suggest that the modulatory effect of endogenous dopamine on adenohypophyseal hormones secretion is variable and selective throughout the normal menstrual cycle. PMID- 2107655 TI - Studies on gas tension in the normal middle ear. Gas chromatographic analysis and a new sampling technique. AB - In studying mechanisms regulating the middle ear pressure it is essential to know the gas compositions of the middle ear. We have constructed a device which made it possible to sample middle ear gas without creating a negative pressure, thus eliminating the risk of admixture of atmospheric air. The samples were analysed by gas chromatography. In 26 normal subjects we found relatively stable values of carbon dioxide (median 52 mmHg, range 31-69 mmHg) and nitrogen (median 605 mmHg, range 563-627 mmHg). The values of oxygen were more fluctuating (median 54 mmHg, range 23-111 mmHg). In 10 of the subjects, arterial gases were determined simultaneously. No correlation could be shown between middle ear and arterial oxygen and carbon dioxide tensions. This investigation provides evidence contradicting the classical theory of a high negative middle ear pressure in Eustachian tube closure. We found strong indications that the Eustachian tube plays an active role in regulating the pressure in the normal middle ear, but variations in blood flow through the middle ear capillaries may also be an important regulating factor. PMID- 2107656 TI - Cerebral oedema complicating diabetic ketoacidosis. AB - Signs of raised intracranial pressure (ICP) developed during treatment of diabetic ketoacidosis in a young child. A CT scan revealed cerebral oedema and direct measurement confirmed elevated ICP. Aggressive treatment was successful in maintaining cerebral perfusion pressure. The child survived with mild handicap in contrast to the poor outcome of previous reports. PMID- 2107657 TI - Influence of strain and sex on the local development of mammary tumors induced by direct application of DMBA powder to rat mammary glands. AB - In order to determine the influence of strain and sex on local carcinogenesis in rat mammary tissue, 1 mg of 7,12-dimethylbenz(a)anthracene (DMBA) was dusted directly onto the exposed mammary gland of 30-day-old Long-Evans (L-E) rats and Sprague-Dawley (S-D) rats. The experiment was terminated 28 weeks after application of the carcinogen. Tumors measuring between 1 and 2 cm in diameter were harvested from female L-E rats with high frequency (85%) and long latency (mean: 23.7 weeks after DMBA dusting), and from female S-D rats with extremely high frequency (98%) and short latency (16.7 weeks). Male rats of both strains were almost identically much less susceptible to DMBA (L-E; 55%, 25.0 weeks, S-D; 53%, 23.9 weeks). Ovariectomized S-D (47%, 24.9 weeks) and orchiectomized S-D (30%, 24.8 weeks) rats, which were gonadectomized at 30 days of age, respectively, were also much less susceptible. A variety of histologies, mostly malignant epithelial, mesenchymal or mixed tumors, were noted in each group. The carcinomatous response in the mammary tissue was much higher in female S-D (96%) than in female L-E (50%) rats, and very low in male and gonadectomized rats (10 20%). In contrast, the sarcomatous response in the mammary tissue was moderate in female and male L-E and male S-D (43-50%) rats, and low in the other groups (15 29%). PMID- 2107658 TI - Stimulation of renin release by PGE2 and PGI2 infusion in the dog: enhancing effect of ureteral occlusion or administration of ethacrynic acid. AB - This study on 19 anaesthetized dogs had two objectives. The first was to compare the potencies of PGE2 and PGI2 as stimulators of renin release and demonstrate their dependency on activation of intrarenal mechanisms for renin release. The second objective was to demonstrate that ethacrynic acid (ECA) increases renin release not as a stimulator, but by activating intrarenal mechanisms. After inhibiting renal prostaglandin synthesis by indomethacin, PGE2 and PGI2 infused into the aorta proximal to the renal arteries exerted no significant effects on renin release, but increased renin release during ureteral occlusion. At equimolar infusion rates, PGI2 increased renin release twice as much as PGE2, but this difference in potency may reflect differences in degradation since 86% of PGE2 and 29% of PGI2 (measured as 6-keto-PGF1 alpha) were degraded during one passage through the kidney. By infusing PGF2 at 8 nmol min-1 and PGI2 at 2 nmol min-1 renin release increased equally and the prostaglandin outputs increased to the same levels as during ureteral occlusion before indomethacin administration. ECA did not increase renin release after indomethacin administration. However, infusion of PGE2 during continuous ECA administration increased renin release in a dose-dependent manner similar to the experiments performed during ureteral occlusion. We conclude that PGI2 and PGE2 in the amounts synthesized in the kidney seem to be equally important stimulators of renin release but their relative potencies cannot be determined because the site of degradation is uncertain. Renin release is enhanced by intrarenal mechanisms activated by ECA infusion or ureteral occlusion, which both cause autoregulatory vasodilation and reduce NaCl reabsorption at the macula densa. PMID- 2107659 TI - Unusual luminescent properties of odd- and even-substituted naphthyl-derivatized dioxetanes. AB - With the advent of enzymatically induced chemiluminescence and improved instrumentation for luminometry, ultrasensitive detection of a wide variety of analytes is now possible using standard immunoassay and DNA probe formats. Model molecular orbital calculations and literature precedent suggest that the singlet efficiencies observed upon decomposition of dioxetanes appended with donor substituted aromatic moieties are dependent on substitution pattern. We have recently discovered, in a series of 3-(2'-spiroadamantane)-4-methoxy-4 acetoxynaphth-2'-yl-1,2-+ ++dioxetanes, that enzymatic generation of a non conjugated, charge transfer excited state results in luminescence of markedly different properties than that observed from an isomeric, conjugated excited state. An example of the former type, 3-(2'-spiroadamantane)-4-methoxy-4-(7" acetoxy)naphth-2'-yl- 1,2- dioxetane (1) emitting at 550 nm, not only provides an increase in phi CL, but exhibits a dramatic bathochromic shift of 80-110 nm from the 460 nm emission of the conjugated isomer 3-(2'-spiroadamantane)-4-methoxy-4 (6"-acetoxy)naphth-2'-yl- 1,2-dioxetane (2). These developments, along with the attendant glow-type luminescence kinetics displayed during the enzymatic decomposition of the new 'odd-pattern' dioxetane, allow the design of simple protocols capable of simultaneous or 'multichannel' detection of several analytes. PMID- 2107660 TI - Magnesium-dependent induction of phagocytosis-associated chemiluminescence of adherent human polymorphonuclear leukocytes by non-opsonized zymosan. AB - A severe dysfunction in the cellular response of human polymorphonuclear leukocytes (PMNL) to non-opsonized zymosan was observed under a deficiency of extracellular Mg2+. The phagocytosis-association native (luminol-independent) luminescence (NL), as well as luminol-dependent luminescence (LDL) (detected simultaneously and discriminated by spectral methods), was strongly inhibited. Apart from a general decrease of total light production, a Mg2+-concentration dependent delay of the maximum of NL and LDL was observed. A disorder in recruitment of activated membrane-bound NADPH-oxidase of PMNL is suggested. The presence of extracellular Ca2+ did not compensate for the Mg2+ deficit. In the presence of Mg2+ only a slight Ca2+-dependent reduction of NL was obtained, but Ca2+ seemed to selectively promote LDL. This may indicate a positive influence of Ca2+ on the myeloperoxidase release from the cells. Experiments with the metalions-chelating agents EDTA and EGTA, which complex Mg2+ to differing extents, confirmed the important role of Mg2+ in PMNL-activation by non-opsonized zymosan. PMID- 2107661 TI - Radiologic evaluation of the solitary pulmonary nodule. PMID- 2107662 TI - Does knowledge of the clinical history affect the accuracy of chest radiograph interpretation? AB - To examine the effect that a concise, objective, and potentially computer extractable history would have on diagnostic accuracy in the interpretation of chest radiographs, we designed and tested a computerized patient-history form that could be integrated realistically into the clinical environment. We performed a series of studies in which 247 posteroanterior normal (79) and abnormal (168) chest radiographs were interpreted by four board-certified radiologists, both with and without accompanying clinical histories. The radiologists recorded their confidence rating of the presence or absence of one or more of the following abnormalities: interstitial disease, nodule, and pneumothorax. Analysis of receiver operating characteristics showed that, with the exception of interpretation of one abnormality by one radiologist, there were no statistically significant differences (p less than .05) between cases interpreted with and without the history form for any of the radiologists. The results of our study suggest that knowledge of clinical history does not affect the accuracy of chest radiograph interpretations for the detection of interstitial disease, nodules, and pneumothoraces. These results may not be applicable to other clinical situations. PMID- 2107663 TI - New mammography screen/film combinations: imaging characteristics and radiation dose. AB - Five types of film (Kodak OM, Kodak OM-SO177, Konica CM, Dupont Microvision, and Fuji MiMa) exposed in combination with seven different intensifying screens (Min R, Min R Medium, Siemens Orthox MA, Kyokka HR Mammo Fine, Agfa Gevaert Detail S (old and new), and Konica Monarch) were processed for either 90 sec (at 33.3 degrees C) or 3 min (at 35.0 degrees C). The films imaged a Computerized Imaging Reference System phantom with additional detail test objects placed on its surface to produce four groups of objects with which to evaluate resolution and contrast. For objects that tested resolution, the Kyokka HR Mammo Fine (Fuji) screen was statistically significantly superior; for objects that tested contrast, the Konica Monarch screen was statistically significantly superior. Extended processing did not affect Dupont and Kodak OM film as much as it affected the other films. It did affect contrast for the other films tested. The mean glandular doses from gridless exposures ranged from 32 to 80 mrad (0.32-0.80 mGy) over all film/screen/processing combinations for a 4.5-cm-thick test object. Several new film/screen combinations can provide images superior to the Kodak Min R/OM combination at a reduced radiation dose. The Kyokka HR Mammo Fine (Fuji) screen was found statistically superior in radiographic resolution of mammographic test objects and the Konica Monarch screen was found to be superior in defining contrast. PMID- 2107664 TI - Doppler sonography: a noninvasive method for evaluation of hepatic venocclusive disease. AB - Hepatic venocclusive disease is a serious complication associated with chemotherapy and radiation used in bone marrow transplantation patients. In the past, liver biopsy has been the only reliable means of diagnosing venocclusive disease. Biopsy in such patients may be dangerous or impossible because of severe coagulopathies. The purpose of our study was to evaluate duplex Doppler sonography in diagnosing hepatic venocclusive disease. We measured the blood velocity and flow in the portal vein, hepatic vein, and inferior vena cava of six patients who were histologically proved to have developed hepatic venocclusive disease after bone marrow transplantation. There were three men and three women with a mean age of 32 years (range, 21-44 years). Examination with Doppler sonography suggested the diagnosis a mean of 41 days (range, 11-62 days) after transplantation. In three patients, the diagnosis was suggested by reversed or "to and fro" flow in the portal vein. In the other three patients, the diagnosis was suggested by a decreased flow in the portal vein. One of these patients with decreased flow had subclinical hepatic venocclusive disease. In this patient, it was not the absolute level of flow but the decrease from a baseline established before ablative therapy that suggested the diagnosis. The amplitude of pulsatility in the hepatic veins appeared to decrease with the onset of venocclusive disease. In the hepatic veins and inferior vena cava, flow toward the heart was maintained. Our findings suggest that duplex Doppler sonography may be useful in detection of hepatic venocclusive disease. We speculate that, with wider experience, Doppler sonographic detection of decreased or reversed flow in the portal vein, in the proper clinical setting, may provide a noninvasive means of reliably diagnosing hepatic venocclusive disease in patients too ill to undergo liver biopsy. PMID- 2107665 TI - Fluoroscopically guided percutaneous gastrostomy and gastroenterostomy: analysis of 158 consecutive cases. AB - We reviewed our experience with 158 consecutive patients who underwent either percutaneous gastrostomy or percutaneous gastroenterostomy during a 2-year period. The catheters used included Foley catheters (36), Cope-type gastric catheters (86), or Carey-Alzate-Coons gastrojejunostomy catheters (36). Gastrojejunostomy tubes were placed in patients with gastroesophageal reflux or aspiration, gastric atony, or partial gastric obstruction. Ninety percent of the tubes were placed for feeding purposes. The technical success rate was 100%. Thirty-day follow-up was obtained in 89%. Thirty-day mortality was 26%, reflecting the substantial number of debilitated patients. No deaths were directly related to tube placement. Major morbidity was 6% and included hemorrhage, peritonitis, tube migration, and sepsis. Minor morbidity was 12%. There was no difference in 30-day mortality or feeding tolerance between the tube types (p less than .05). Patients with Foley catheters had more complications necessitating surgical intervention and an increased incidence of tube changes required within 30 days. These were the only statistically significant differences between the tubes (p less than .05). Our results show that percutaneous gastrostomy is a safe and effective means of gastroenteric feeding or decompression. Because of the fewer complications and ease of insertion, the Cope type of gastrostomy tube has become our preferred catheter for percutaneous feeding or decompression. PMID- 2107666 TI - Pictorial essay. Imaging of and intervention for biliary complications after hepatic transplantation. PMID- 2107667 TI - Selective osteal salpingography and transvaginal catheter dilatation in the diagnosis and treatment of fallopian tube obstruction. AB - Selective salpingography and transvaginal catheter dilatation were performed in 157 women with infertility to diagnose, localize, and classify obstructive diseases of the fallopian tubes and to correct obstruction of the proximal (uterine-end) tube. In 61 (39%) of the patients, the selective salpingograms showed patent tubes despite the fact that two previous hysterosalpingograms showed obstruction of the proximal (uterine-end) tube. Transvaginal catheter dilatation successfully recanalized the proximal portion of the tubes in 79 (82%) of 96 patients with obstructed tubes. In 18 of 25 with successful transvaginal catheter dilatation and 6-month follow-up salpingography, the tubes remained patent. Coexisting disease of the distal (ovarian-end) tubes was diagnosed in 29 (18%) of the patients. Pregnancy was achieved in 11 of the 157 patients (six in whom obstructions were corrected by transvaginal catheter dilatation and five in whom selective salpingograms showed patent tubes). There were no complications due to the procedure. The excellent diagnostic and therapeutic yield, lack of complications, and low cost justify the use of these percutaneous techniques to investigate female infertility and to treat obstruction of the uterine end of the fallopian tube. PMID- 2107668 TI - Uterine perforation simulating urachal carcinoma: CT diagnosis. PMID- 2107669 TI - Early and late bone-marrow changes after irradiation: MR evaluation. AB - Knowledge of the chronologic evolution of bone-marrow changes during and after radiation therapy is essential in differentiating normal postradiation changes from other marrow abnormalities. The appearance of the lumbar vertebral bone marrow was studied on 55 serial spin-echo and short-T1 inversion-recovery (STIR) MR images obtained in 14 patients receiving radiation therapy for Hodgkin disease, seminoma, or prostate carcinoma. Images were obtained before, at weekly intervals during, and at various monthly intervals up to 14 months after a 3- to 6-week course of fractionated paravertebral lymph-node irradiation of 1500-5000 rad (15-50 Gy). During the first 2 weeks of therapy, there was no definite change in the appearance of the marrow on spin-echo images; however, there was an increase in signal intensity on the STIR images, apparently reflecting early marrow edema and necrosis. Between weeks 3 and 6, the marrow showed an increasingly heterogenous signal and prominence of the signal from central marrow fat, shown best on T1-weighted images. Late marrow patterns (6 weeks to 14 months after therapy) varied and consisted of either homogenous fatty replacement or a band pattern of peripheral intermediate signal intensity, possibly representing hematopoietic marrow surrounding the central marrow fat. No focal marrow lesions or soft-tissue edema were identified during the course of radiation therapy; their presence should raise the possibility of the presence of a pathologic process other than radiation change. These data suggest that MR can detect radiation-induced marrow changes as early as 2 weeks after starting therapy, and that there are at least two distinct types of late marrow MR patterns. PMID- 2107670 TI - Cervical spondylolysis: imaging findings in 12 patients. AB - Cervical spondylolysis is defined as a corticated cleft between the superior and inferior articular facets of the articular pilar, the cervical equivalent of the pars interarticularis in the lumbar spine. Associated dysplastic changes and spina bifida suggest that the lesion is congenital. It is a rare condition; only 70 cases have been previously reported in the world literature. Recognition of this disorder and differentiation from traumatic articular pilar fracture or dislocation is of paramount importance in patients who have had cervical spine trauma. The present study details radiologic features in 12 patients 20-80 years old with cervical spondylolysis. Plain film radiologic findings were correlated with hypocycloidal high-resolution tomography (nine patients), CT (six patients), and MR imaging (one patient). Seven patients had spondylolysis at C6 (three bilateral) and five had the abnormality at C4 (all unilateral). Nine of 12 patients were initially misdiagnosed. Characteristic radiologic features include (1) a well-marginated cleft between the facets, (2) a triangular configuration of the pilar fragments on either side of the spondylolytic defect, (3) posterior displacement of the dorsal triangular pillar fragment, (4) hypoplasia of the ipsilateral pedicle, (5) spina bifida at the involved level, and (6) compensatory hyper- or hypoplasia of the ipsilateral articular pillars at the level above and/or below the defect. A multistudy approach was often necessary to demonstrate these findings. Heightened awareness of the radiologic features of cervical spondylolysis should allow one to differentiate it from articular pillar fracture or dislocation. PMID- 2107671 TI - Traumatic lumbar hernia: CT diagnosis. AB - A lumbar hernia usually involves protrusion of extraperitoneal fat or bowel through an area of weakness in the posterolateral abdominal wall bounded superiorly by the 12th rib, inferiorly by the iliac crest, posteriorly by the erector spinae muscle, and anteriorly by the posterior border of the external oblique muscle. Most are due to an acquired nontraumatic or congenital cause. Acute blunt abdominal trauma is a rare cause of lumbar hernia; to our knowledge, the CT diagnosis of this variety has not been reported. Since 1985, approximately 850 patients have undergone emergent abdominal CT for evaluation of acute abdominal trauma at our hospital; in seven of these patients, a traumatic lumbar hernia was diagnosed prospectively. In three patients, CT showed a flank hematoma with herniation of bowel through the lumbar triangle. CT showed pelvic fractures in three other patients, accompanied by herniation of bowel in one patient, herniation of extraperitoneal fat in another, and herniation of extraperitoneal fat and blood in the third. One patient had both a flank hematoma and a pelvic fracture with herniation of bowel. Acute traumatic lumbar hernia is a rare but significant abnormality that should be considered in patients with blunt abdominal trauma, especially in those with large flank hematomas and pelvic fractures. The hernia contents, associated injuries, and disrupted muscle layers are all well demonstrated on CT. PMID- 2107672 TI - CT diagnosis of posterior perineal hernia. PMID- 2107673 TI - The value of MR imaging in monitoring the effect of chemotherapy on bone sarcomas. AB - We studied the value of MR imaging in monitoring the response of Ewing sarcoma and osteosarcoma to chemotherapy. Relative signal-intensity changes on MR images in the course of chemotherapy were compared with changes in tumor volume and histopathologic findings. MR scans (T1- and T2-weighted spin-echo images) were obtained in 20 patients with bone sarcoma. The first MR scan was obtained before the administration of chemotherapy in all patients. The follow-up scan was obtained in the course of treatment, before surgery. Tumor-volume and signal intensity measurements of the intra- and extraosseous components of the tumor were analyzed. In 17 patients, histopathologic findings of the resected tumor were available for comparison with the MR images. In 12 of 17 patients there was complete agreement between changes in tumor volume, changes in the signal intensity of the extraosseous tumor component on T2-weighted images, and histopathology. In another four cases, changes in signal intensity correlated either with histopathology or with changes in tumor volume. In one patient with a pathologic fracture, no such correlation existed. A significant correlation was found between changes in signal intensities and pathologic response (r = .57, p = .02), as well as between changes in tumor volume and pathologic response (r = .53, p = .03). No correlation could be found between changes in signal intensity of the intraosseous tumor component and changes in tumor volume or histopathology. We conclude that the signal intensity of the extraosseous component of bone sarcomas on T2-weighted MR images in addition to changes in tumor volume may be useful in evaluating response to chemotherapy. PMID- 2107674 TI - Pictorial essay. MR imaging of sacral and presacral lesions. PMID- 2107675 TI - MR of the shoulder with a 0.2-T permanent-magnet unit. PMID- 2107676 TI - Diagnostic quality of portable abdominal radiographs in neonates with necrotizing enterocolitis: digitized vs nondigitized images. AB - Digital manipulation of radiographic images has prompted significant interest because of the potential for improving image quality and diagnostic accuracy. We compared conventional and digital radiographs in the evaluation of neonatal necrotizing enterocolitis (NEC). Fifty abdominal radiographs in neonates with suspected or autopsy-confirmed NEC and 50 similar radiographs of neonates without suspicion of NEC were digitized. Definition of intraabdominal anatomy was optimized by window width and level adjustment. Hard-copy radiographs of the digitally manipulated images were then produced by a laser printer. Twelve general radiologists each evaluated, without benefit of clinical information, a random mixture of 50 cases of NEC and normal controls, with both conventional and digital images for each case, for a total of 100 radiographs reviewed. Each image was evaluated for overall suspicion of NEC and the presence and severity of six radiographic signs of NEC. The radiologists also rated their confidence in their assessments. The results were compared with those from a similar analysis by an experienced pediatric radiologist to ensure validity of image evaluation. No statistically significant differences were found between the conventional and digital imaging formats for the assessment of the signs of NEC (p = .15) or for determination of the overall suspicion of NEC (p = .07). Our results show the digitized and the conventional, nondigitized radiographs to be at least equally useful for evaluating the radiographic signs of NEC and suggesting an appropriate diagnosis. PMID- 2107677 TI - Doppler evaluation of renal transplants in children: a prospective analysis with histopathologic correlation. AB - Duplex Doppler sonography recently has been used to evaluate renal transplants. Some authors have stated that high resistive indexes (RIs) occur in the presence of acute renal transplant rejection. RIs less than 0.7 are considered as probably excluding acute transplant rejection. We performed a prospective study of duplex sonographic examinations of pediatric patients (mean age, 8 years; 13 boys, two girls) with renal allografts and clinically suspected transplant disease. The results of 22 duplex studies were correlated with histopathologic data obtained between July 1987 and June 1988. RIs of the arcuate arteries in patients with acute rejection (n = 14) averaged 0.62 (range, 0.50-0.80). The RI in patients with chronic rejection (n = 1) was 0.59. RIs in patients with acute tubular necrosis (n = 3) averaged 0.66 (range, 0.59-0.72). RIs in patients with cyclosporine A toxicity (n = 4) averaged 0.66 (range, 0.58-0.79). Tubulointerstitial rejection was predominant, with only two patients showing minimal acute vascular rejection. Thirteen of 14 pediatric patients with histologically proved renal transplant rejection had a resistive index of less than 0.70. This study refutes the concept that resistive indexes of less than 0.7 exclude acute rejection. PMID- 2107678 TI - Coronary angiography of pulmonary atresia, hypoplastic right ventricle, and ventriculocoronary communications. AB - A retrospective study was undertaken to determine the spectrum of angiographic abnormalities of the coronary arteries in infants and children with pulmonary atresia, hypoplastic right ventricle, and right ventriculocoronary arterial communications. Twenty-nine patients with 67 angiographic examinations were reviewed; findings in seven patients were compared with those at autopsy. Twenty seven (93%) of 29 patients had caliber abnormalities of the involved coronary arteries, including obstructive lesions in 20 (69%) of 29 and segmental dilatation in 16 (55%) of 29. Nine patients had interruption of the anterior descending artery and one had absent connection between the coronary arteries and the aorta. A single coronary artery was found in four of 29 patients. There was excellent correlation between clinical angiography and autopsy findings in seven patients. This study confirms the ability of high-quality clinical angiography to show significant abnormalities of the coronary arteries in infants and children with pulmonary atresia and ventriculocoronary communications. PMID- 2107679 TI - Pictorial essay. Current evaluation of the patient with abnormal visceroatrial situs. AB - Patients suspected of having derangement of solitus asymmetry should be evaluated individually to determine abdominal visceral and vascular arrangement and to investigate associated problems. This evaluation should begin with plain films to assess cardiac and gastric positions and pulmonary vascularity. Assessment of the bronchial branching patterns should be attempted in all cases. Sonography will delineate the presence or absence of splenic tissue and the anatomy and relationships of the cava and the portal vein. When no spleen is found and the pulmonary vascularity appears congested, a subdiaphragmatic total anomalous pulmonary venous connection should be suspected and verified. If there are splenuli in the retrogastric area, particular attention should be paid to the status of the gallbladder, especially in children who do not have congenital heart disease. Selective spleen scans can confirm the presence of splenic tissue. The high cost and sedation requirement of MR would suggest that it be reserved for cases in which sonography is unable to answer the pertinent questions. PMID- 2107680 TI - Cervical and basicranial diastematomyelia. PMID- 2107681 TI - Gd-DTPA-enhanced MR imaging of the brain in patients with meningitis: comparison with CT. AB - Plain and Gd-DTPA-enhanced MR images of the brain were obtained in 18 consecutive patients with meningitis (eight with tuberculous, five with bacterial, three with viral, and two with fungal infections); the MR images were compared with CT scans. MR images were obtained on a 2.0-T superconducting unit with both T1- and T2-weighted pulse sequences before injection and with a T1-weighted sequence after injection of Gd-DTPA (0.1 mmol/kg) in all patients. In tuberculous meningitis, MR imaging depicted ischemia/infarct, hemorrhagic infarct of basal ganglia, meningeal enhancement at either basal cistern or convexity surface of brain, and associated small granulomas in a few more patients than CT did. In bacterial meningitis, primary foci of extracranial inflammation (i.e., mastoid, paranasal sinuses) and adjacent intracranial lesions including localized dural inflammation, subdural fluid collection, and/or brain parenchymal lesions were demonstrated much better on MR than on CT. Otherwise, MR images generally matched the CT scan. Although the plain MR images, both T1- and T2-weighted, were the most sensitive in delineating ischemia/infarct, hemorrhage, and edema, they were not as specific as Gd-DTPA-enhanced T1-weighted images and postcontrast CT scans in defining the active inflammatory process of the meninges and focal lesions precisely. We conclude that if Gd-DTPA is used, MR imaging appears to be superior to CT in the evaluation of patients with suspected meningitis. Precontrast MR is needed to delineate ischemia/infarct, edema, and subacute hemorrhage. PMID- 2107682 TI - Age-related changes in the cervical facet joints: studies with cryomicrotomy, MR, and CT. AB - The cervical facet joints of 20 cadavers were studied systematically with MR, CT, cryomicrotomy, and histologic sections to determine the anatomic changes that occur with age. Uniform layers of cartilage and subarticular cortical bone characterize the cervical facet joints in cadavers under 20 years of age. Most adult cervical facet joints have only a discolored or microscopically thin layer of cartilage and have irregularly thickened subarticular cortical bone. The appearance of the cervical facet joints changes significantly with aging. PMID- 2107683 TI - Lumbar disk herniation and canal stenosis: value of intraoperative sonography in diagnosis and surgical management. AB - One hundred four patients with preoperative diagnoses of lumbar canal stenosis, disk herniation, or a combination of both were evaluated with intraoperative sonography with the intent of (1) describing the sonographic characteristics of herniated disks and distinguishing these from bulging anuli, epidural fat, scar tissue, and spondylolisthesis; (2) establishing criteria for adequate decompression of canal stenosis; and (3) determining the usefulness of sonography in monitoring disk removal. Disk material demonstrates medium echogenicity, different in its sonographic features from bone, epidural fat, scar tissue, and epidural veins. A sonographic diagnosis of disk herniation was made in 43 cases, 41 of which were confirmed during surgery. Sonography established the presence or absence of disk herniation (confirmed by surgery) in 14 of 19 patients who had equivocal preoperative findings. After routine diskectomy, residual disk material was found in 17 (41%) of 41 patients, which led to further surgery in 16 patients with removal of the additional disk fragments. In 84 patients undergoing decompressive surgery for canal stenosis, sonography detected residual canal compression in 19 (23%), which led to a widened decompression in 15 of these patients. Sonography can differentiate disk material from other normal or abnormal structures in the canal; therefore, sonographic monitoring helps to ensure adequate bony decompression and complete diskectomy. We conclude that intraoperative sonography is an important tool in the surgical management of lumbar disk disease and stenosis. PMID- 2107684 TI - Primary cerebral neuroblastoma: CT and MR findings in 12 cases. AB - A retrospective CT, MR, and clinical study was performed in 12 patients, five children and seven adults, with histologically proved primary CNS neuroblastoma. The CT and MR appearances of this neoplasia were more variable than generally recognized. Although seven tumors were predominantly intraparenchymal masses with calcification and cyst formation, five were intra- or juxtaventricular. CT was preferable to noncontrast MR both at initial diagnosis and follow-up for identification of calcification, recurrent tumor at surgical sites, and leptomeningeal disease. Noncontrast MR was useful primarily for localization of peri- and intraventricular lesions. We conclude that primary CNS neuroblastoma has a more variable radiographic appearance than is generally recognized, and that an intra- or periventricular epicenter is common. PMID- 2107685 TI - Intracranial ependymoma and subependymoma: MR manifestations. AB - In order to provide a detailed description of the MR appearance of intracranial ependymoma, the MR examinations of 12 patients (10 with ependymomas and two with subependymomas) were reviewed and correlated with operative and pathologic reports. Three of 10 ependymomas were intraventricular, two were intraparenchymal, and five were transependymal, extending from CSF spaces into parenchyma. Both subependymomas were intraventricular. Solid ependymomas and subependymomas were iso- to hypointense relative to normal white matter on T1 weighted images and hyperintense on proton-density- and T2-weighted images. Foci of signal heterogeneity within solid neoplasms represented methemoglobin, hemosiderin, necrosis, calcification, and encased native vessels or tumor vascularity. Gd-DTPA-enhanced images in two patients differentiated enhancing tumor from surrounding nonenhancing edema and from surrounding normal brain parenchyma. Cystic neoplasms had sharply defined, round or oval margins and uniform signal intensity equivalent to or slightly hyperintense relative to CSF. Tumor-associated calcification was not demonstrated readily by MR. Sagittal and coronal images were valuable in assessing the amount of intraventricular tumor and route of extension. We conclude that the MR differentiation of ependymomas and subependymomas from other gliomas is provided most reliably by the location and morphology of the tumor and not by differences in signal intensity. The typical ependymoma arises within the fourth ventricle as a solid mass with heterogeneous signal intensity. A propensity for spread is seen along the CSF pathways via the foramina of Magendie and Luschka and the aqueduct of Sylvius. Supratentorial ependymomas may be periventricular in location and have cystic components. The two subependymomas in our series were solid, intraventricular tumors with relatively homogeneous signal intensities. PMID- 2107686 TI - A simple phantom for learning needle placement for sonographically guided biopsy. PMID- 2107687 TI - Endovaginal sonography for guidance in draining pelvic fluid collections. PMID- 2107688 TI - Lower-extremity venous thrombosis in patients with acute hip fractures: determination of anatomic location and time of onset with compression sonography. AB - Patients with acute hip fractures are at increased risk for the development of lower-extremity deep venous thrombosis and its major complication, pulmonary embolism. It is furthermore recognized that the risk of clinically important pulmonary embolism depends to some degree on the anatomic location of the preexisting thrombosis. Because of the increased risk of thromboembolic disease, most patients with hip fracture are treated with one of several prophylactic regimens. The potential for effective prophylaxis may depend on the time of onset of the venous thrombosis. We used compression sonography to determine the anatomic location and time of onset of deep venous thrombosis in patients with hip fractures being treated with antithrombotic prophylaxis. Ninety-six patients had compression sonography of the injured extremity perioperatively and serially until discharge. Ninety-three also were examined with contrast venography when the sonogram suggested thrombus or at discharge if all sonograms were normal. Twenty areas of thrombus were identified in 18 patients, thereby yielding a prevalence of thrombosis of 19%. All patients were asymptomatic. Above-knee clot was diagnosed in 14 (78%) of these 18 patients. Nine (64%) of the 14 patients with significant clot had the abnormality on their first perioperative investigation (in eight of nine cases, the clot was adjacent to the fracture site), before any means of prophylaxis could have been initiated. Significant thrombosis developed in six patients later in their course (in only one case was the clot related to the fracture site), and the thrombus was an extension of below-knee clot in the minority of the patients. We conclude that although currently acceptable prophylaxis may decrease the frequency of thrombosis, it does little to prevent above-knee clot, which often antedates the initiation of therapy. Furthermore, as the clinical diagnosis of deep venous thrombosis is difficult in patients with acute hip fracture, serial compression sonograms are recommended so that patients with unsuspected clot may be treated with appropriate anticoagulation and/or caval interruption. PMID- 2107689 TI - Early detection of saphenous vein arterial bypass graft stenosis by color assisted duplex sonography: a prospective study. AB - We propose a simple and rapid technique for the postoperative surveillance of developing stenosis in lower extremity saphenous vein arterial bypass grafts that uses color-assisted duplex sonography. Color Doppler flow images are used to identify points of altered flow dynamics. These points are subsequently analyzed by duplex sonography, with doubling of the peak systolic velocity at the point of suspected stenosis considered the diagnostic threshold for significant stenosis. A segment-by-segment comparison made with arteriography in 14 patients (15 grafts, 92 segments) showed this approach to be 95% sensitive (18/19) and 100% specific (73/73) for the detection and localization of focal graft stenoses that involve greater than 50% narrowing of the lumen diameter. We conclude that color assisted duplex sonography can accurately detect the presence of saphenous vein arterial bypass graft stenoses. PMID- 2107690 TI - Performing JCAHO dose calculations with the aid of a microcomputer spreadsheet program. PMID- 2107691 TI - Attitudes of American radiologists toward their practices: present and future. PMID- 2107692 TI - Autoradiology: patient heal thyself. AB - All in all, our program has been a great success, endorsed by everyone from patients to health care providers and hospital administrators. The PPP will revolutionize diagnostic and interventional radiologic procedures and will free the radiologist to perform more critical maneuvers--the out-of-department lunch, the extended afternoon off, and perfection of the golf swing. PMID- 2107693 TI - Upper lobe collapse due to endobronchial sarcoidosis. PMID- 2107694 TI - Coronary artery-left ventricle fistula. PMID- 2107695 TI - MR imaging of congenitally corrected transposition of the great vessels in adults. PMID- 2107696 TI - Castleman disease in a mother and daughter. PMID- 2107697 TI - Breast mass simulation on a mammogram. PMID- 2107698 TI - Sonography of extramedullary hematopoiesis of the liver. PMID- 2107700 TI - Follow-up of endovascular stented renal artery. PMID- 2107699 TI - Portal vein MR angiography. PMID- 2107701 TI - Metastatic carcinoma of the proximal femur closely resembling hematopoietic hyperplasia on MR. PMID- 2107703 TI - The radiologic hedge. PMID- 2107702 TI - Spontaneous resolution of a nuchal fetal cystic hygroma diagnosed early in the second trimester of pregnancy. PMID- 2107704 TI - CT diagnosis of foot-in-mouth disease. PMID- 2107706 TI - A dose of one's own medicine. PMID- 2107705 TI - My experience as a patient with subarachnoid hemorrhage. PMID- 2107707 TI - Treatment of carotid artery aneurysms with platinum coils: an experimental study in dogs. AB - The objectives of this study were to investigate the consistency, patency, and natural history of a vein graft canine aneurysm model and to determine the effectiveness of various coil designs on inducing aneurysm thrombosis. Twenty-one sacculuslike aneurysms were created in mongrel dogs by anastomosing a vein pouch to the common carotid artery. The model produced wide-neck aneurysms with 100% patency. The canine vein graft aneurysm provided an excellent model for the evaluation of endovascular devices. Three types of specially designed platinum coils were placed in the aneurysms: those with simple curves, those with complex curves, and those with flower petal curves and silk fibers. These coils were placed by the endovascular route by means of microcatheters. Flower petal coils with silk fibers were effective in producing thrombosis of the aneurysms, suggesting that coils of the appropriate design may be useful in the endovascular treatment of aneurysms. The other coil designs evaluated, those with simple and complex curves without silk fibers, demonstrated insufficient thrombogenicity and spatial stability. PMID- 2107708 TI - Aneurysms of the petrous portion of the internal carotid artery: results of treatment with endovascular or surgical occlusion. AB - Seven patients with symptomatic aneurysms involving the petrous segment of the internal carotid artery were treated by endovascular techniques (six patients) or surgical ligation (one patient). Patients' ages at the time of treatment ranged from 7 to 62 years (mean, 30 years). The presenting symptoms were pain (seven patients), eighth nerve dysfunction (three patients), seventh nerve dysfunction (one patient), fifth nerve dysfunction (two patients), and bruit (one patient). Two patients, ages 7 and 19, respectively, presented with giant, partially thrombosed petrous aneurysms and had hemiatrophy of the body ipsilateral to the side of the aneurysm. Only one patient had a history of trauma; aneurysms in the remaining patients were presumed to be congenital in origin. In one patient with a saccular aneurysm, a balloon could be navigated into the aneurysm, obliterating it but preserving the parent artery. The remaining six patients had fusiform aneurysms with intraluminal thrombus and underwent proximal occlusion (four patients) or trapping procedure (two patients). In all patients, symptoms were alleviated after thrombosis of the aneurysm. The only complication was a transient visual loss in a hypercoagulable patient, occurring after carotid occlusion. Petrous carotid aneurysms can produce a wide clinical spectrum of signs and symptoms in younger patients; these aneurysms frequently are fusiform and contain chronic thrombus. They can be treated effectively by endovascular or surgical occlusive procedures. PMID- 2107709 TI - Carotid artery disease assessed by color Doppler flow imaging: correlation with standard Doppler sonography and angiography. AB - Carotid artery disease was assessed in 180 patients by means of color Doppler flow imaging. Color Doppler findings in 360 carotid arteries were compared with the results of standard Doppler sonography, and color Doppler findings in 60 bifurcations were compared with the results of intraarterial angiography. The sensitivity of color Doppler for the detection of carotid disease was 100% when compared with angiography. The accuracy of color Doppler in classifying minor (40 60%), moderate (61-80%), and severe (81-90%) stenosis ranged from 91.3% to 97.8% vs standard Doppler sonography, and from 91.7% to 95.8% vs angiography. Whereas all occlusions were identified correctly by both color Doppler and angiography, four pseudoocclusions of the carotid artery were misdiagnosed as occluded. Characteristic features providing reliable criteria of the degree of stenosis are (1) intensity, extent, and duration of color fading; (2) postprocessed systolic peak frequency; (3) plaque extent on serial sonograms; and (4) poststenotic flow patterns. Display of hemodynamic disturbances induced by less pronounced plaques showed highly variable patterns that could not be anticipated from the plaque morphology alone. Thus, color Doppler preserves the advantages of standard Doppler and duplex sonography but provides additional information about otherwise anechoic necrotic and thrombotic material that often causes cerebral embolisms. With atherogenesis, repair mechanisms may be sustained or progression be stopped by reducing the risk factors and instituting medical treatment; thus, the application of this noninvasive technique is important. PMID- 2107710 TI - Ferromagnetism and MR imaging: safety of carotid vascular clamps. AB - Metallic extracranial carotid vascular clamps of the Selverstone, Crutchfield, Poppen-Blaylock, Salibi, Kindt, and tantalum varieties have been placed for treatment of large, giant, or inoperable intracranial aneurysms. To ascertain what adverse effect, if any, MR imaging would have on these clamps, magnetic deflection at 1.5 T was measured for various carotid clamps. Marked magnetic deflection (and torque) was displayed by stainless steel Poppen-Blaylock clamps. Relatively mild magnetic deflection was displayed by the stainless steel Selverstone, Salibi, Crutchfield, and Kindt clamps. Three patients with previously placed carotid clamps (two Selverstone, one Salibi) and one patient with a nonferromagnetic tantalum carotid clip had cranial or cervical MR studies at field strengths ranging from 0.35 to 0.60 T. No patient experienced any discomfort or neurologic sequelae as a result of MR imaging. Although the ferromagnetic clamps created severe "black-hole" artifacts and image distortion within the cervical and facial regions, no significant image degradation was apparent during spin-echo imaging of the brain. The tantalum clip created a far smaller MR artifact than did ferromagnetic clamps and allowed effective spin-echo and gradient-echo imaging in the cervical region. Our findings indicate that most patients with carotid vascular clamps (and nonferromagnetic clips) can probably be imaged safely with MR. PMID- 2107711 TI - Leukoaraiosis: correlation of MR and CT findings with blood flow, atrophy, and cognition. AB - Hypodense periventricular white-matter lesions detected by CT (leukoaraiosis) and high-intensity T2 signals detected by MR imaging were correlated with measurements of local cerebral blood flow (LCBF), cerebral atrophy, and cognitive performance. Subjects studied included elderly volunteers who were neurologically normal (n = 6), patients with chronic cerebral infarctions and intact cognition (n = 2), patients with multiinfarct dementia (n = 14), and patients with Alzheimer dementia (n = 9). Leukoaraiosis correlated with periventricular high intensity lesions detected by MR, LCBF reductions, cognitive impairments, and cerebral atrophy. Moderate to severe leukoaraiosis was associated with LCBF reductions in the cortex, basal ganglia, and frontal white matter. Periventricular MR lesions correlated with cerebral atrophy but not with cognitive impairments or reductions in LCBF. The exquisite sensitivity of MR revealed small lesions that did not correlate with LCBF reductions and cognitive impairments. Remote subcortical white-matter lesions detected by MR did not correlate with periventricular MR lesions, leukoaraiosis, LCBF, cerebral atrophy, or cognitive performance, indicating little clinical relevance. We concluded that diffuse cerebral hypoperfusion, particularly in combination with the poor collateral circulation of white matter surrounding the lateral ventricles, is responsible for leukoaraiosis. PMID- 2107712 TI - MR signal abnormalities in memory disorder and dementia. AB - MR imaging of the brain, performed in 86 normal subjects and 113 patients with objective memory disorder or dementia, demonstrated white- and gray-matter areas of high signal intensity on long TR images (short and long TE). Hyperintensities were analyzed with respect to size (on a scale of 0-3) and location: lesions were periventricular, subcortical, or cortical. The patients with memory disorder and dementia were categorized as having probable/possible Alzheimer disease, a combination of Alzheimer disease and multiinfarct cognitive disorder, or multiinfarct cognitive disorder alone on the basis of clinically determined Hachinski ischemic scores. Significant correlations were found between age and scores for periventricular lesions (r = .40, p less than .0005) and subcortical lesions (r = .39, p less than .0005) in normal subjects. Correlations were also found between the Hachinski ischemic score and scores for periventricular lesions (r = .21, p less than .01), subcortical lesions (r = .27, p less than .0002), and cortical lesions (r = .32, p less than .0005) in subjects with memory disorder/dementia. Comparing multiinfarct cognitive disorder, Alzheimer disease, and normal groups, the mean scores for periventricular lesions were 12.0 +/- 4.6, 7.6 +/- 4.8, and 3.4 +/- 2.6, while mean scores for subcortical lesions were 10.8 +/- 12.2, 4.1 +/- 6.4, and 0.8 +/- 1.2, respectively. Periventricular lesions were present in 99-100% of patients with Alzheimer disease and multiinfarct cognitive disorder. On the other hand, subcortical lesions, which were identified in 100% of patients with multiinfarct cognitive disorder, were present in only about half of the patients with Alzheimer disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107713 TI - MR of intracranial epidermoid tumors: correlation of in vivo imaging with in vitro 13C spectroscopy. AB - We analyzed the MR findings of five patients with benign intracranial epithelial tumors, commonly called epidermoids. The neoplasms were categorized into two groups on the basis of T1-weighted MR signal intensity (relative to brain): high signal-intensity masses (short T1) and low-signal-intensity masses (long T1). Surgical specimens were obtained and analyzed by means of 13C MR spectroscopy. Epidermoids with short T1 values (white epidermoids) had a high lipid content comprising mixed triglycerides containing unsaturated fatty acid residues. Epidermoids with long T1 values (black epidermoids) exhibited a much reduced lipid content with no triglycerides or fatty acids. There was evidence of trace amounts of cholesterol in the black epidermoids. Our data indicate that epidermoids are a heterogeneous group of neoplasms that behave differently with T1-weighted MR imaging and 13C MR spectroscopy. The combination of MR imaging and spectroscopy holds the potential of further elucidating the nature of epidermoids as well as of other forms of neoplasms. PMID- 2107714 TI - The effect of Gd-dimeglumine on subcutaneous tissues: a study with rats. AB - Gadopentetate dimeglumine and a saline solution of similar osmolality of 2100 mOs/kg H2O were placed in the paws and in the thigh muscles and subcutaneous tissue of Sprague-Dawley rats weighing 225-250 g. The paws were serially photographed for 4 weeks and the thighs were examined histologically for up to 4 weeks. Gross and histologic reactions to gadopentetate dimeglumine were greater than those to the saline solution, and included tissue sloughs. When risk factors for extravascular extravasation are present, such as infusion sites in the dorsum of the hand or foot, or around the ankle, or when soft tissues are obscured by bandages, caution should be exercised when injecting gadopentetate dimeglumine. PMID- 2107715 TI - Gd-DTPA-enhanced MR imaging of leptomeningeal spread of primary intracranial CNS tumor in children. AB - Three children with known primary brain neoplasms and leptomeningeal disease were evaluated with MR imaging. Two of the patients had medulloblastoma and one had pineoblastoma. The presence of leptomeningeal tumor spread was established by positive CSF cytopathology in conjunction with compatible contrast-enhanced CT findings. Contrast-enhanced CT, nonenhanced MR, and Gd-DTPA-enhanced MR studies were then compared. In two cases, leptomeningeal lesions were seen better with Gd DTPA-enhanced MR than with contrast-enhanced CT. In all three cases, Gd-DTPA MR imaging revealed lesions that were not identified on noncontrast MR. Gd-DTPA enhanced MR imaging is useful when searching for intracranial leptomeningeal tumor deposits in pediatric patients at risk for this condition. PMID- 2107716 TI - MR evaluation of brain iron in children with cerebral infarction. AB - Young children and infants normally have essentially no detectable brain iron. We evaluated brain iron patterns on 23 MR scans in 20 patients under 6 years of age with clinical and MR-documented cerebral infarctions in an attempt to further understand the neuropathologic phenomenon of increased iron deposition, which has been observed in other disease states. MR was performed at 1.5 T with spin-echo sequences from 1 day to 4 years after infarction. MR scans were interpreted without knowledge of clinical information and were assessed for (1) location and character (i.e., bland or hemorrhagic) of infarct, and (2) nonheme iron (i.e., marked hypointensity on long TR/TE images) in the basal ganglia, red nuclei, substantia nigra, thalami, dentate nuclei, and deep white matter. Sixteen of 20 infarctions were associated with increased iron. Six of seven cases with unilateral iron deposition had ipsilateral infarctions. The location (deep versus cortical) and age of the infarction had no apparent bearing on iron patterns. We conclude that increased brain iron is commonly associated with cerebral infarction and is nonspecific, rather than a marker of movement disorders. Since iron may arise from either interruption of transport pathways or directly from cell injury and, in fact, iron itself may propagate the tissue injury, this finding may have important clinical and pathophysiologic implications in ischemic brain injury. PMID- 2107717 TI - Subgaleal dermoid cyst of the anterior fontanelle: diagnosis with sonography. AB - We report the plain film and sonographic findings in six children (2 1/2 months to 5 years old) with a subgaleal dermoid cyst at the anterior fontanelle. Plain films of the skull made in all patients showed a soft-tissue mass superficial to the anterior fontanelle with a normal subcutaneous fat layer above it. In three children, the margins of the anterior fontanelle were beveled to match the contour of the mass. Sonography in the five children with open fontanelles showed the mass to have a well-defined sonolucent interior with a clear wall separating it from the superior sagittal sinus and other intracranial contents. The combination of clinical evaluation, plain films, and sonography appears to be sufficient to make the diagnosis of subgaleal dermoid cyst of the anterior fontanelle. PMID- 2107718 TI - Imaging of MR-compatible intracerebral depth electrodes. PMID- 2107719 TI - Posttraumatic cerebral infarction diagnosed by CT: prevalence, origin, and outcome. AB - Posttraumatic cerebral infarction is a recognized complication of craniocerebral trauma, but its frequency, cause, and influence on mortality are not well defined. To ascertain this information, all cranial CT studies demonstrating posttraumatic cerebral infarction and performed during a 40-month period at our trauma center were reviewed. Posttraumatic cerebral infarction was diagnosed by CT within 24 hr of admission (10 patients) and up to 14 days after admission (mean, 3 days) in 25 (1.9%) of 1332 patients who required cranial CT for trauma during the period. Infarcts, in well-defined arterial distributions, were diagnosed either uni- or bilaterally in the posterior cerebral (17), proximal and/or distal anterior cerebral (11), middle cerebral (11), lenticulostriate/thalamoperforating (nine), anterior choroidal (three), and/or vertebrobasilar (two) territories in 23 patients. Two other patients displayed atypical infarction patterns with sharply marginated cortical and subcortical low densities crossing typical vascular territories. CT findings suggested direct vascular compression due to mass effects from edema, contusion, and intra- or extraaxial hematoma as the cause of infarction in 24 patients; there was postmortem verification in five. In one patient, a skull-base fracture crossing the precavernous carotid canal led to occlusion of the internal carotid artery and ipsilateral cerebral infarction. Mortality in craniocerebral trauma with complicating posttraumatic cerebral infarction, 68% in this series, did not differ significantly from that in craniocerebral trauma patients without posttraumatic cerebral infarction when matched for admission Glasgow Coma Score results. Thus, aggressive management should be considered even in the presence of posttraumatic cerebral infarction. PMID- 2107720 TI - CT evaluation of anaplastic thyroid carcinoma. AB - CT findings in 19 patients with anaplastic thyroid carcinoma were compared retrospectively with pathologic findings and the results of palpation. The carcinoma appeared as a large mass of low attenuation accompanied by dense calcification in 58% of the patients; there was necrosis in 74%. Often, adjacent structures were infiltrated. CT correctly showed tumor invasion of the carotid artery (7/7), internal jugular vein (9/10), larynx (5/6), trachea (8/10), esophagus (4/5), mediastinum (5/5), and regional lymph nodes (14/16). Seven patients (50%) had necrotic nodes. CT was superior to palpation in the detection of a primary tumor in one patient and of metastatic nodes in seven patients. It suggested a suitable place for biopsy in two patients, leading to a correct diagnosis. CT altered surgical planning in five patients with intrathoracic extension of the thyroid tumor, and in three patients with laryngeal or esophageal invasion of the tumor. CT can increase diagnostic accuracy in patients with anaplastic thyroid carcinoma by suggesting a likely diagnosis and by indicating an appropriate site for biopsy. It is indispensable in the planning of surgery for patients with this disorder. PMID- 2107721 TI - Measurements of the normal cervical spinal cord on MR imaging. AB - The purpose of this study was to determine normal measurements of the C1-T3 spinal cord in anteroposterior and transverse planes from MR images and to compare these with previously published data. Seven hundred and fifty-six measurements were made from 66 randomly selected MR studies of the cervical spine. We measured the anteroposterior and transverse diameters of the cord at each vertebral level and computed the simple product of these diameters to provide a single useful numerical value, termed the approximate cord area (ACA). The cord varies in average anteroposterior and transverse diameters from 8.8 mm x 12.4 mm at C2 to 8.7 mm x 14 mm at C4 to 7.4 mm x 11.4 mm at C7. The cervical enlargement was found from C4 to C6 and was most evident by comparing the ACA values. At C2 the average ACA was 110 mm2, at C4 it was 121.9 mm2, and at C7 the average ACA was 84.6 mm2. Comparison of our data with the literature reveals disparate measurements that vary up to 6 mm from our mean values. However, our results correlated well with the postmortem studies of Nordquist (1964). A single number cannot be used as the basis for evaluating spinal cord size. Each level should be compared with the normal range specific for that level. PMID- 2107722 TI - Pseudoatrophy of the cervical portion of the spinal cord on MR images: a manifestation of the truncation artifact? AB - Routine evaluation of axial MR images of the cervical spine with high-intensity CSF (long TR/TE spin-echo or gradient-echo images) revealed apparent narrowing of the cord's anteroposterior diameter when these images were compared with corresponding postmyelography CT scans. This discrepancy was believed to be due to the truncation artifact at the CSF-cord boundary. To examine the truncation effect, we compared cord diameters in 12 patients on postmyelography CT scans and MR images and then compared these with MR scans of normal volunteers and of an agar-saline spine phantom. There was an artifactual diminution of the cord diameter in the 128-step phase-encoding axis of the 128 x 256-matrix MR scan as compared with the diameter of the cord in the patients' postiohexol CT scans and in the 256 phase-encoded axis MR scan in the volunteer study. A similar discrepancy was noted in the spine phantom study, in which the cord diameter in the 256-step phase-encoded MR scan, the CT scan, and direct measurement exceeded that in the 128-step phase-encoded axis MR scan. The range of differences between the measurements was as large as 2.3 mm (patients), 1.7 mm (volunteers), and 1.8 mm (phantom) for the three studies. In all three studies, varying the photographic window width and level produced variation in the apparent cord diameter of up to 1.5 mm. To eliminate this effect, the cord diameters in the phantom and the normal control subjects were measured at identical window levels. The truncation artifact, coupled with standard window settings used in photography, may lead to inaccurate display of the diameter of the cervical spinal cord. PMID- 2107723 TI - Compatibility of cervical spine braces with MR imaging: a study of nine nonferrous devices. AB - Several cervical spine braces and orthoses were evaluated for their compatibility with imaging in the MR scanner. Nine such devices were investigated: EXO cervical collar, Philadelphia collar, S.O.M.I. cervical orthosis, Guilford cervical orthosis, modified Guilford cervical orthosis, PMT halo cervical orthosis, modified PMT halo cervical orthosis, Bremer halo system, and Bremer MR-compatible halo system. Devices containing ferrous materials detected by a small bar magnet were not scanned. The remaining devices applied to a volunteer or a patient were scanned to evaluate image quality in the generation of images of the cervical spine and, in some cases, the brain. Orthoses that contained electrically conductive loops produced unsatisfactory scans. Replacement of ferrous materials with nonferrous metals and alloys and elimination of electrical loops proved to be necessary to make cervical braces and orthoses MR-compatible. Cervical orthoses with aluminum or graphite-carbon composite components that are interconnected with plastic joints such as the plastic ball-and-socket joints are, to date, the most successfully designed devices for MR compatibility. To make these orthoses CT compatible, low electron density materials are presently being evaluated to replace the titanium skull pins. PMID- 2107724 TI - Automated percutaneous biopsy in postoperative diskitis: a new method. PMID- 2107725 TI - Cervical epidural hematomas: CT diagnosis in two cases that resolved spontaneously. PMID- 2107726 TI - CT and MR imaging of Canavan disease. PMID- 2107727 TI - MR imaging of leukoencephalopathy associated with Navajo neuropathy. PMID- 2107728 TI - Gd-DTPA-enhanced MR imaging of cochlear schwannoma. PMID- 2107729 TI - Ramsay Hunt syndrome mimicking intracanalicular acoustic neuroma on contrast enhanced MR. PMID- 2107730 TI - MR demonstration of pituitary hyperplasia and regression after therapy for hypothyroidism. PMID- 2107731 TI - Gd-DTPA enhancement in CNS extramedullary hematopoiesis. PMID- 2107733 TI - Lumbar disk degeneration in spinal dysraphism. PMID- 2107732 TI - Herpes trigeminal neuritis and rhombencephalitis on Gd-DTPA-enhanced MR imaging. PMID- 2107734 TI - A case-control study on the association between first trimester exposure to lithium and Ebstein's anomaly. PMID- 2107735 TI - Effects of dosing intervals on the development of tolerance to high dose transdermal nitroglycerin. PMID- 2107736 TI - Clinical benefits and cost-effectiveness of lowering serum cholesterol levels: the case of simvastatin and cholestyramine in The Netherlands. AB - To assess the cost-effectiveness of cholesterol-reducing therapy with cholestyramine and simvastatin in the primary prevention of coronary artery disease in The Netherlands, a model of coronary artery disease incidence was used based on multivariate logistic risk functions from the Framingham study. For men with initial cholesterol levels of 8 mmol/liter, the cost per year of life saved of cholestyramine, expressed in Dutch guilders (NLG; 1 NLG = $0.50), ranges from approximately NLG 208,000 to NLG 483,000, depending on the patient's age at initiation of therapy. For simvastatin, cost-effectiveness ranges from NLG 46,000 to NLG 98,000 per year of life saved among this group of men. Similar differences between simvastatin and cholestyramine therapy prevail among women, although the costs per year of life saved for both agents are considerably higher. These results suggest that (1) simvastatin is substantially more cost effective than is cholestyramine; (2) simvastatin therapy compares favorably with other generally accepted medical practices, especially if treatment is initiated at an early age; and (3) as its long-term safety record becomes more established, simvastatin may become accepted as a drug of first choice in the treatment of persons with elevated serum cholesterol levels. PMID- 2107737 TI - Foodborne Snow Mountain agent gastroenteritis with secondary person-to-person spread in a retirement community. AB - A variety of small round-structured viruses are being recognized with increasing frequency as a cause of gastroenteritis in the community, but have rarely been reported to cause outbreaks in hospitals or extended-care facilities. From March 20 through April 15, 1988, an outbreak of gastroenteritis occurred in a retirement facility in the San Francisco Bay area. Illness was characterized by diarrhea, nausea, and vomiting; two residents died. Attack rates were 46% (155 of 336) in residents and 37% (28 of 75) in employees. During the initial outbreak period, illness among residents was associated with two shrimp meals served in the facility dining hall (odds ratio = 6.7). Person-to-person transmission probably occurred: The risk of becoming ill one or two days after a roommate became ill was significantly greater than that of becoming ill at other times during the outbreak (risk ratio = 6.5). Microbiologic examinations for bacterial and parasitic enteric pathogens were negative; however, 27-nm viral particles were detected by immune electron microscopy and by blocking enzyme immunoassay to Snow Mountain agent in stools obtained at the onset of illness from one of six ill residents. Seroconversion (greater than fourfold antibody rise) to Snow Mountain agent was detected in acute- and convalescent-phase serum specimens from five of six ill residents as measured by enzyme immunoassay, but not for Norwalk agent as measured by radioimmunoassay. This report of an outbreak of Snow Mountain agent gastroenteritis in an extended-care facility documents that these difficult-to-identify 27-nm viruses can cause outbreaks in inpatient settings. PMID- 2107738 TI - Reduced serum haptoglobin values in hemophiliacs receiving monoclonally purified factor VIII concentrates. AB - Hemophiliacs often have mild anemia, and hemolysis has been suggested as the likely mechanism on the basis of the reduced serum haptoglobin values frequently observed in these patients. It has been suggested that hypohaptoglobinemia results from isohemagglutinins or other contaminating proteins in the infused factor concentrates. The advent and increased utilization of Factor VIII concentrates that are highly purified by use of monoclonal antibodies have provided the opportunity to study whether proteins other than Factor VIII contained in the concentrate induce hemolysis. Of 49 consecutively studied Factor VIII-deficient hemophiliacs, 19 (39%) had a reduced serum haptoglobin level (less than 27 mg/dl). In particular, 16 of 35 (46%) of patients receiving only monoclonally purified Factor VIII products (Monoclate or Hemofil-M) had a reduced serum haptoglobin value. Haptoglobin measurements were variable on repeat measurement in 8 patients. Haptoglobin levels did not correlate with type or severity of hemophilia, hemoglobin value, or alterations in liver function. Low serum haptoglobin values were also observed in children with leukemia, without apparent hemolysis, who had extensive cutaneous hemorrhage associated with thrombocytopenia. We propose that reduced serum haptoglobin values in hemophiliacs do not result from immune-mediated hemolysis due to contaminating proteins in the concentrate. Moreover, hypohaptoglobinemia may not be due to hemolysis at all but may instead result from dissolution of hematomas and other foci of internal hemorrhage. PMID- 2107740 TI - Compatibility of drugs separated by a fluid barrier in a retrograde intravenous infusion system. PMID- 2107739 TI - A splice-junction mutation responsible for familial apolipoprotein A-II deficiency. AB - The first case of familial apolipoprotein A-II (apo A-II) deficiency was recently reported from Hiroshima, Japan, and designated apo A-IIHiroshima. The proband had no immunologically detectable apo A-II in her plasma. DNA sequence analysis showed that the proband was homozygous for a G----A transition at position 1 of intron 3 of the apo A-II gene. A sister of the proband, who had an intermediate level of plasma apo AII, was shown to be heterozygous for this base substitution. This splice-junction alteration is most likely responsible for apo A-II deficiency, since it would be expected to completely block splicing of intron 3 from the primary transcript and therefore prevent formation of functional mRNA. This deficiency seems to have little influence either on lipid and lipoprotein profiles or on the occurrence of coronary artery disease. PMID- 2107741 TI - Visual and spectrophotometric determination of compatibility of alteplase and streptokinase with other injectable drugs. PMID- 2107742 TI - Hyperkalemia in diabetic ketoacidosis. AB - Patients with diabetic ketoacidosis tend to have somewhat elevated serum K+ concentrations despite decreased body K+ content. The hyperkalemia was previously attributed mainly to acidemia. However, recent studies have suggested that "organic acidemias" (such as that produced by infusing beta-hydroxybutyric acid) may not cause hyperkalemia. To learn which, if any, routinely measured biochemical indices might correlate with the finding of hyperkalemia in diabetic ketoacidosis, we analyzed the initial pre-treatment values in 131 episodes in 91 patients. Serum K+ correlated independently and significantly (p less than 0.001) with blood pH (r = -0.39), serum urea N (r = 0.38) and the anion gap (r = 0.41). The mean serum K+ among the men was 5.55 mmol/l, significantly higher than among the women, 5.09 mmol/l (p less than 0.005). Twelve of the 16 patients with serum K+ greater than or equal to 6.5 mmol/l were men, as were all eight patients with serum K+ greater than or equal to 7.0 mmol/l. Those differences paralleled a significantly higher mean serum urea N concentration among the men (15.1 mmol/l) than the women (11.2 mmol/l, p less than 0.01). The greater tendency to hyperkalemia among the men in this series may have been due partly to their greater renal dysfunction during the acute illness. However, other factors that were not assessed, such as cell K+ release associated with protein catabolism, and insulin deficiency per se, may also have affected serum K+ in these patients. PMID- 2107743 TI - Hydralazine does not stimulate prostacyclin biosynthesis in hypertensive patients. AB - The hypothesis that vascular prostacyclin synthesis is stimulated by the oral administration of hydralazine and may account for part of its vascular effect was tested. Eight white patients with mild essential hypertension were studied in a randomized, double-blind design to assess the effects of indomethacin on hydralazine's ability to lower blood pressure, elevate pulse, and alter the vascular prostacyclin biosynthesis as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto prostaglandin F1 alpha (PGF1 alpha) measured by gas chromatography-mass spectrometry. Administration of hydralazine at either 50 mg bid or 100 mg bid for a week, doses commonly administered in clinical settings, was not associated with a statistically significant fall in mean blood pressure, although there was a tendency towards a decrease but did result in an increase in heart rate. Administration of indomethacin had no effect on the hemodynamic parameters secondary to hydralazine. Administration of indomethacin resulted in a slight but significant weight gain compared to placebo, but the addition of hydralazine did not result in a further increase in weight. Neither dose of hydralazine resulted in an increase in the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha. The excretion rate was 85 +/- 16 ng/g of creatinine during placebo, 88 +/- 16 ng/g of creatinine during hydralazine, 50 mg bid, and 65 +/- 8 ng/g of creatinine during hydralazine, 100 mg bid. Administration of indomethacin, 50 mg bid, resulted in a significant decrease in 2,3-dinor-6-keto-PGF1 alpha from 65 +/- 6 ng/g to 37 +/- 8 ng/g of creatinine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107744 TI - Platelet count in normal, small, and anemic fetuses. AB - A reference range for fetal platelet count with gestation was established from the study of samples obtained by cordocentesis from 229 pregnancies that had prenatal diagnosis. The mean platelet count increased from 187 +/- 47 x 10(9)/L at 15 weeks to 274 +/- 47 x 10(9)/L at 40 weeks' gestation. In 113 red cell isoimmunized pregnancies, the moderately anemic fetuses were significantly thrombocythenic, whereas the severely anemic fetuses were thrombocytopenic. In 136 small-for-gestational-age fetuses the platelet count was reduced and there were significant correlations between the magnitude of the thrombocytopenia and the degree of fetal smallness, hypoxemia, and acidemia. PMID- 2107745 TI - Ovulation and successful pregnancy in a woman with ovarian failure after hypophysectomy and gonadotropin therapy. AB - A 38-year-old woman ovulated and conceived after administration of human menopausal gonadotropins despite a previous diagnosis of ovarian failure at age 18. Possible explanations include restoration of down-regulated gonadotropin receptors by development of a prolactinoma, spontaneous remission of autoimmune oophoritis, or prior tumor secretion of biologically inert gonadotropins. PMID- 2107746 TI - Severe acidosis and subsequent neurologic status. AB - To examine the relationship between severe acidosis at birth and evidence of subsequent neurologic dysfunction, a 4-year review was performed encompassing 15,528 neonates. One hundred forty-two (0.91%) of these neonates had an umbilical cord arterial pH less than or equal to 7.05 with a base deficit greater than or equal to mEq/L. Neurologic assessments found 101 of 110 term neonates (91.8%) and 17 of 32 preterm neonates (53.1%) with severe acidosis to be free of neurologic deficits at the time of hospital discharge. Follow-up developmental evaluation data were available for 7 of 9 term neonates and 8 of 15 preterm neonates with abnormal examinations. Although 5 term and 6 preterm infants demonstrated mild developmental delays or mild tone abnormalities in the first year of life, none exhibited a major motor or cognitive abnormality at 12 to 24 months of age. Consequently, acidosis in umbilical cord blood, even when severe, is a poor predictor of subsequent neurologic dysfunction. PMID- 2107747 TI - Induction of HLA-DR expression on human myoblasts with interferon-gamma. AB - Myoblast transplantation is an experimental therapy that may be useful in hereditary muscle diseases. One obstacle to this approach is immune rejection. We evaluated human myoblasts and myotubes for surface expression of HLA class I and II histocompatibility antigens. The myoblast preparations, cultured from muscle biopsy specimens, were more than 95% pure as assessed by immunostaining with the Leu19 monoclonal antibody that reacts with human myoblasts and regenerating muscle fibers. Myoblasts and myotubes constitutively expressed HLA-class I but not HLA-class II molecules. However, HLA-class II expression was induced on mononucleated myoblasts after culture for 5 days in the presence of recombinant human interferon-gamma. The results indicate that transplanted myoblasts can be rejected because of histoincompatibility at the HLA-class I and HLA class II locus. Furthermore, an aberrant expression of HLA-class II antigen on myoblasts in vivo may play a role in the pathogenesis of autoimmune muscle disorders. PMID- 2107748 TI - Steady-state pHi, buffering power, and effect of CO2 in a smooth muscle-like cell line. AB - Intracellular pH (pHi) was studied in the smooth muscle-like cell line, BC3H-1, using the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5,6 carboxyfluorescein (BCECF). The initial pHi measured in 20 mM Na N-2 hydroxyethylpiperazine-N'-2 ethanesulfonic acid-buffered medium [NHB; external pH (pHo) 7.4, 37 degrees C] was 6.89 +/- 0.01 (n = 178). pHi was affected by changes in external pHo, pHi changing by approximately 70% of the change in pHo. The intrinsic buffering power (beta int) of these cells, measured either with NH4Cl or Na propionate pulses, is low for muscle cells, averaging approximately 10 mM/pH unit. Steady-state pHi of BC3H-1 cells in NHB acidified reversibly on exposure to 0.5 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 1.4 +/ 0.3 x 10(-4) pH/s), 1 mM amiloride (2.0 +/- 0.7 x 10(-4) pH/s), or Na-free solution (8.3 +/- 2.4 x 10(-4) pH/s) and alkalinized upon exposure to Cl-free solutions (9.7 +/- 2.2 x 10(-4) pH/s). Exposure of BC3H-1 cells to CO2-HCO3 buffered solutions resulted in a transient acidification followed by an alkalinization of 0.3-0.4 pH unit to a new steady-state pHi of 7.27 +/- 0.01 (n = 65). This new steady-state pHi acidified very slowly upon exposure to 1 mM amiloride (0.3 +/- 0.1 x 10(-4) pH/s), acidified more rapidly upon exposure to 0.5 mM DIDS (5.9 +/- 0.6 x 10(-4) pH/s) or Na-free solutions (9.8 +/- 1.0 x 10( 4) pH/s), and alkalinized on exposure to Cl-free solutions (24.5 +/- 1.3 x 10(-4) pH/s).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107749 TI - pH regulatory transport systems in a smooth muscle-like cell line. AB - The membrane transport systems responsible for pH regulation in BC3H-1 cells were studied using the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5,6 carboxyfluorescein (BCECF). In nominally CO2-free Na N-2-hydroxyethylpiperazine N'-2-ethanesulfonic acid buffer (NHB) recovery from acidification after an NH4Cl pulse was reversibly inhibited by 1 mM amiloride or by Na-free solutions. On exposure to 5% CO2-HCO3 (external pH constant at 7.4), BC3H-1 cells alkalinized by approximately 0.3-0.4 pH unit. This CO2-induced alkalinization was unaffected by 1 mM amiloride, markedly reduced by 0.5 mM 4-acetamido-4'-isothiocyanostilbene 2,2'-disulfonic acid (SITS), and inhibited by Na-free solutions. On readdition of Na, cells rapidly alkalinized, even in the presence of 1 mM amiloride. Exposure to Cl-free CO2-HCO3 solutions caused a rapid alkalinization of nearly 1 pH unit that was abolished by SITS, largely independent of Na, unaffected by amiloride, and unchanged by membrane depolarization in high external K solutions. CO2 induced alkalinization was slowed by approximately 75% after prolonged exposure of cells to Cl-free NHB, but a distinct recovery from acidification remained in these Cl-depleted cells. This recovery was Na-dependent, SITS-inhibitable, and unaffected by depolarization in high-K solutions. In the presence of CO2, the acidification seen in response to NH4Cl-induced alkalinization was reduced 50% by 0.5 mM SITS. These data suggest that the regulation of pH in BC3H-1 cells is mediated by at least three transport systems: 1) Na-H exchange; 2) Cl-HCO3 exchange; and 3) electroneutral (Na + HCO3)-Cl exchange.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107750 TI - Halothane-dependent release of intracellular Ca2+ in blood cells in malignant hyperthermia. AB - The concentration of ionized cytosolic calcium [( Ca2+]i) was determined in peripheral blood mononuclear cells from normal and malignant hyperthermia (MH) susceptible humans and pigs, using the fluorescent Ca2+ indicator indo-1. [Ca2+]i was slightly but significantly elevated in cells from MH human cells relative to normal cells (198 +/- 18 nM, n = 15, and 146 +/- 14 nM, n = 11, respectively, P less than 0.05). Anesthetic concentrations of halothane in the cell suspension resulted in a rapid increase in [Ca2+]i in cells from both normal and MH humans or pigs. The increases (delta) were more pronounced in cells from MH subjects than from normal individuals (delta at 5.7 mM halothane: 245 +/- 53 vs. 57 +/- 11 nM, respectively) and from MH than from normal pigs (delta of 241 +/- 63 vs. 53 +/- 27 nM, respectively). Removal of extracellular Ca2+ obliterated the delta[Ca2+]i caused by halothane in cells from normal humans or pigs but only decreased by about half the delta[Ca2+]i in cells from MH humans or pigs. In 1,2 bis-(aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-loaded cells, in the absence of extracellular Ca2+, halothane failed to increase [Ca2+]i. This suggests that buffering Cai2+ with BAPTA precludes detection of release of Ca2+ from intracellular stores, explaining the previous observations made with quin2, a highly chelating Ca2+ indicator. It is concluded that clinical concentrations of halothane allow influx of Ca2+ in cells from both normal and MH-susceptible individuals but release Ca2+ from intracellular stores selectively in cells from the latter group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107751 TI - Dissociation between myosin phosphorylation and shortening velocity in canine trachea. AB - The relationship between glycogen phosphorylase activity (an index of cytosolic Ca2+ content), myosin light-chain phosphorylation, isotonic shortening velocity, and isometric tension was examined in canine trachealis. Responses were measured in tracheal strips contracted with various concentrations of methacholine or K+. Both agonists produced prolonged and concentration-dependent increases in isometric tension that reached 90% of the plateau level within 1 (methacholine) to 5 (K+) min and remained stable over 60 min. In contrast to the monotonic increase in isometric tension, shortening velocity reached a maximum almost immediately (12-48 s) after the addition of either methacholine or K+ and then declined over time to a steady-state level that was 25-40% of the peak. Phosphorylase activity also increased transiently, reaching a maximum 1-2 min after the addition of either agonist before declining to near-basal levels over the 60-min observation period. Unlike the increases in shortening velocity and phosphorylase activity, agonist-induced myosin phosphorylation was not markedly transient. Moreover, regardless of the contractile agonist used, no correlation was found between myosin phosphorylation and shortening velocity when these parameters were compared at corresponding time points. This suggests that myosin phosphorylation is not the sole determinant of shortening velocity in canine trachealis. PMID- 2107752 TI - A thermodynamic model of hemoglobin suitable for physiological applications. AB - We propose a quantitative model of the thermodynamics of hemoglobin in contact with its five major ligands (O2, CO2, Cl-, 2,3-bisphosphoglycerate, and H+). Our model incorporates the two-state formalism of J. Monod, J. Wyman, and J.P. Changeux (J. Mol. Biol. 12: 88-118, 1965) for treatment of quanternary transitions and also the mean field formalism of K. Linderstrom-Lang (C. R. Trav. Lab. Carlsberg Ser. Chim. 15: 1-30, 1924) for treatment of electrostatic interactions. On the basis of this approach, we develop an algorithm for the efficient computation of observable quantities, such as the occupancy of various ligand binding sites, and an objective statistical procedure for determining both maximum likelihood values and confidence limits of all the intrinsic thermodynamic parameters of hemoglobin. Finally, we show that the predictions of our theory are in good agreement with independent experimental observations. PMID- 2107753 TI - Stable incorporation of a bacterial gene into adult rat skeletal muscle in vivo. AB - We have developed a novel technique to incorporate and stably express foreign genes in adult rat skeletal muscle in vivo. Endogeneous satellite cells in skeletal muscle regenerating from bupivacaine damage were infected with an injected retrovirus containing the Escherichia coli beta-galactosidase gene under the promoter control of the Moloney murine leukemia virus long-terminal repeat. Constitutive and stable expression of beta-galactosidase activity was observed in muscle fibers after 6 days and 1 mo of muscle regeneration. Two patterns of expression were observed, diffuse expression within fibers and focal expression associated with the sarcolemma. This technique will allow future experiments with muscle-specific genes and promoters to study the physiological regulation of skeletal muscle gene expression in the intact adult mammal. Furthermore, the technique of stimulating stem cell proliferation to allow retroviral-mediated gene transfer may be generally applicable to other tissues. PMID- 2107754 TI - Isolation and incubation conditions to study heart mitochondrial protein synthesis. AB - Although much is now known with regard to the processes of mammalian mitochondrial gene expression, relatively little is known concerning the quantitative regulation of this pathway in response to hormones or other physiological stimuli. This has been caused, in large part, by the lack of adequate assay systems in which such processes can be meaningfully measured. The purpose of this and the companion paper [E. E. McKee, B. L. Grier, G. S. Thompson, A. C. F. Leung, and J. D. McCourt. Am. J. Physiol. 258 [Endocrinol. Metab. 21):E503-E510, 1990] is to describe a system in which the quantitative regulation of mitochondrial protein synthesis in rat heart can be investigated. In this report the conditions for mitochondrial isolation and labeling are described, and the importance of isolating intact, tightly coupled mitochondria in obtaining high and reliable rates of protein synthesis is demonstrated. The highest levels of protein synthesis are obtained in mitochondria isolated from hearts perfused and homogenized in the presence of subtilisin, conditions in which the fastest rates of state 3 respiration and the highest respiratory control ratios are also observed. Analysis of the free amino acid pools indicates that isolated heart mitochondria have a negligible level of endogenous methionine as well as other amino acids. As a result, the concentration and specific radioactivity of the [35S]methionine pool serving protein synthesis could be easily determined. Optimal translation occurred at 30 degrees C at a pH of 7.0 7.2 and required the addition of methionine (20 microM), the other 19 amino acids (0.1 mM each), K+ (60-90 mM), Cl- (30-90 mM), Mg2+ (0.5-5 mM), and bovine serum albumin (1 mg/ml). As shown in the companion paper, adenine nucleotide (0.5-4.0 mM) and oxidizable substrate (10-20 mM glutamate) are also required for isolated heart mitochondrial protein synthesis. Analysis of labeled mitochondrial translation products demonstrated that bona fide mitochondrial peptides were synthesized. PMID- 2107755 TI - Hypertonic fluid absorption from rabbit descending colon in vitro. AB - Fluid and solute movements across rabbit distal colonic mucosa were investigated to determine the solute concentration of the absorbate and to characterize the absorption process. With isotonic mucosal and serosal bathing solutions the osmolality of the absorbate was 492 +/- 22 mosmol/kg. When the absorbate concentration was corrected for passive components of water and salt flux, the concentration of the "active" component was 1,062 +/- 206 mosmol/kg. Octanol (2 mM) caused a decrease in net solute and water absorption and in the concentration of the absorbate. Cytochalasin D (20 microM) increased the absorbate tonicity and decreased the hydraulic conductance of the active route for water movement. Correlations were made with measurements of the total crypt and crypt luminal cross-sectional areas. Ouabain, octanol, deoxycholate, and theophylline increase the cross-sectional area of the crypt lumen relative to that of the total crypt. These findings suggest that the hypertonic component of fluid absorption is via the crypts. The large osmotic pressure across the crypt wall could provide the considerable fluid tension (5 atm) required to dehydrate feces. PMID- 2107756 TI - Multiple pathways for the regulation of ornithine decarboxylase in intestinal epithelial cells. AB - The regulation of ornithine decarboxylase (ODC) was examined in an intestinal epithelial crypt cell line (IEC-6). Addition of fetal bovine serum or growth factors to quiescent preconfluent cells resulted in a 20- to 30-fold increase in the specific activity of ODC, which was maximal at approximately 4 h. In contrast, ODC mRNA levels either did not change or increased only twofold over the time period examined. The increased enzymatic activity was blocked by cycloheximide, putrescine, and the calmodulin antagonist N-(6-aminohexyl)-5 chloro-1-napthalinesulfonamide (W-7). Cycloheximide alone increased mRNA levels and potentiated the induction in response to serum, suggesting that protein synthesis is not required for the increase in mRNA accumulation. In contrast to its effect on ODC activity, W-7 was without effect on the serum-stimulated increase in ODC or c-fos mRNA levels. Putrescine decreased ODC activity, but not mRNA content, in a dose-dependent manner with an IC50 between 0.1 and 1.0 microM. Also, serum stimulation resulted in a threefold increase in the stability of the enzyme in the presence of cycloheximide; this effect was blocked by pretreatment with W-7. Enzymatic activity was paralleled by ODC protein content as determined by [3H] difluoromethylornithine binding. Finally, the induction of enzyme activity was due entirely to an increase in Vmax as no detectable change in Km for ornithine was detected. These results suggest that ODC is regulated at multiple levels by independent signaling pathways in cultured intestinal epithelial cells. Increased levels of active ODC protein and enzymatic activity are sensitive to W-7 and putrescine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107757 TI - Influence of acute and chronic respiratory alkalosis on preexisting chronic metabolic alkalosis. AB - The severity of the alkalemia produced by a reduction in arterial carbon dioxide tension (PaCO2) in normal humans and animals is ameliorated by buffer and renal responses that diminish the levels of plasma bicarbonate concentration ([HCO3 ]p). These adjustments have even greater potential importance in preventing extreme degrees of alkalemia when hypocapnia occurs in the presence of an initially elevated [HCO3-]p (mixed respiratory and metabolic alkalosis). The aim of the present study was to characterize the acute (approximately 3 h) and chronic (5 days) acid-base effects of respiratory alkalosis when superimposed on chronic metabolic alkalosis. Ten dogs were made alkalotic by the repeated administration of ethacrynic acid and the provision of a chloride-restricted diet. Hypocapnia (delta PaCO2 = 10 mmHg) was then superimposed by exposing the animals to 11% O2 in an environmental chamber. A large fall in [HCO3-]p occurred in the acute hypocapnic phase that was further augmented in the chronic phase; the corresponding delta [HCO3-]p/delta PaCO2 slopes were 0.43 and 0.71 meq.l 1.mmHg-1, respectively, values substantially larger than those previously reported for hypocapnia in normals as well as in animals with preexisting HCl acidosis. Hyperlactatemia was responsible, on average, for 43% of the decrement in [HCO3-]p during acute hypocapnia but for only 20% of the delta [HCO3-]p during the chronic phase of the study. The striking decrement in [HCO3-]p observed in response to the chronic reduction in PaCO2 was sufficient not only to prevent the development of extreme alkalemia but also to offset entirely the effect of hypocapnia on plasma [H+]. PMID- 2107758 TI - Concentration dependence of urea and thiourea transport in rat inner medullary collecting duct. AB - The vasopressin-dependent urea permeability of the rat terminal inner medullary collecting duct (IMCD) is much greater than can be explained by lipid-phase permeation or paracellular diffusion, suggesting the presence of vasopressin stimulated facilitated transport pathway. We used the isolated perfused tubule technique to test whether the urea transport pathway exhibits saturation characteristics consistent with a facilitated pathway. When the luminal urea concentration was varied between 0 and 800 mM (no urea in peritubular bath), the relationship between the urea flux and the luminal concentration was linear with a y-axis intercept that was not significantly different from zero, indicating an absence of saturation in this concentration range. Higher concentrations of urea could not be tested due to technical limitations. However, when thiourea (a urea analogue that shares the urea transport pathway with urea) was substituted for urea in similar experiments, the apparent thiourea permeability fell with increasing thiourea concentration in the range 10-200 mM, indicative of saturation of the urea-thiourea transporter. When the urea concentration was varied in both bath and lumen, the lumen-to-bath urea flux approached a limiting value at 400-500 mM urea, consistent with saturation of the transporter. However, nonspecific inhibition of urea transport by bath urea could not be ruled out in those experiments. We conclude that the urea and thiourea transport pathway in the terminal IMCD exhibits saturation characteristics. However, the urea concentration required to saturate the pathway is apparently high, at least 400 500 mM in one set of experiments and probably greater than 800 mM in another. PMID- 2107759 TI - [Ca2+]i rises via G protein during regulatory volume decrease in rabbit proximal tubule cells. AB - Although animal cells swell in hypotonic medium, their volume is subsequently regulated by a net loss of KCl via Ca2(+)-dependent channels. A rise in intracellular free calcium ([Ca2+]i) thus appears to be an initial event in the adaptation of external tonicity, although details of this mechanism are not known. To investigate cell volume regulation, we measured [Ca2+]i (by use of fura 2) and cell diameters in single cells of cultured renal proximal convoluted tubule. We found that a rapid rise in [Ca2+]i occurred after cells were exposed to hypotonic solution (250 mosM) from 95.8 +/- 3.8 to 468.2 +/- 24 nM (n = 16). The rise in [Ca2+]i was not observed in cells exposed to Ca2(+)-free medium, and exposure to isotonic high-K or low-Na medium did not elicit a rise in [Ca2+]i, suggesting that this rise was a result of Ca2+ influx and not via voltage dependent Ca2+ influx or decrease of Ca2+ efflux via Na(+)-Ca2+ pump. Pretreatment of cells with pertussis toxin dose dependently blocked the rise in [Ca2+]i. The hypotonic solution enhanced accumulations of inositol tris- and tetra-phosphate after a 1-min exposure. Studies that measured cell diameters suggest that recovery of cell volume may include the rise in [Ca2+]i. These data suggest that the regulatory volume decrease of proximal tubule cells involves a pertussis toxin-sensitive guanine nucleotide binding protein-operated Ca2+ influx. PMID- 2107760 TI - Effect of angiotensin II and norepinephrine on isolated rat afferent and efferent arterioles. AB - Differential sensitivity of the pre- and postglomerular arterial vessels to vasoconstrictor activity of angiotensin II (ANG II) and norepinephrine (NE) is controversial. To avoid the complex extravascular neurohumoral variables that may have accounted for different results in the intact rat kidney, an isolated arteriole technique was used to examine the dose responses of ANG II and NE on afferent (AA) and efferent arterioles (EA) from Sprague-Dawley rats. EA were more sensitive than AA to ANG II (EC50 = 3.2 +/- 1.8 x 10(-11) and 1.0 +/- 1.6 x 10( 9) M, respectively, P less than 0.001), whereas EC50 of both AA and EA to NE were similar (3.4 +/- 2.3 x 10(-8) and 1.4 +/- 2.6 x 10(-8) M, respectively). The dose response curves of AA to ANG II were not different when perfused at different luminal pressures (90 and 30 mmHg). In contrast, EA were more sensitive to ANG II at 30 than at 90 mmHg (3.0 +/- 1.2 x 10(-11) and 5.0 +/- 1.8 x 10(-10) M, respectively, P less than 0.005). The EC50 of EA to NE was unaffected by similar changes in luminal pressures. The mean dose-response curves of AA to ANG II were the same with and without the addition of 10(-5) M indomethacin; however, in arterioles displaying a focal constriction pattern to ANG II the response became uniform. It is concluded that, in the isolated rat glomerular arterioles, EA are more sensitive to ANG II than AA, but both vessels respond similarly to NE. The decreased ANG II sensitivity in AA is not related to the higher in vivo pressure, and the attenuated response in AA does not appear to be mediated primarily through ANG II-stimulated vasodilator prostanoid activity. EA sensitivity to ANG II appears to be inversely related to lumen pressure. PMID- 2107761 TI - Chemotactic peptide FMLP contracts human coronary arteries via cyclooxygenase products. AB - The chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) is a constrictor of bronchial smooth muscle. Recently it has also been shown to contract rabbit coronary arteries by an unknown mechanism. This prompted us to investigate whether the chemotactic peptide has an effect on the tone of human coronary arteries obtained during heart transplantation. FMLP was found to be a potent and efficacious myotropic agent on strips of human coronary artery. Contractions were generally transient and subject to tachyphylaxis. The FMLP induced vasoconstriction was not dependent on the presence of endothelial cells. The response was unaffected by the histamine H1-antagonist diphenhydramine or the antagonist of peptido-leukotrienes FPL 55712. However, the contractions were completely abolished in the presence of the fatty acid cyclooxygenase inhibitors aspirin or indomethacin. Stimulation of rings of human coronary artery with FMLP resulted in a marked production of prostaglandin (PG)F2 alpha, a smaller production of PGD2, and a slight increase in thromboxane B2. All these prostanoids constricted the artery, but the stable thromboxane mimetic U44069 was 100 times more potent than PGF2 alpha or PGD2. These data indicate that FMLP activates cells of unknown identity in the adventitia or media of human coronary arteries to produce a mixture of vasoconstrictor cyclooxygenase products. These compounds are likely to mediate the myotropic effect of FMLP on this artery. The mechanism may participate in the pathogenesis of some forms of coronary vasospasm. PMID- 2107762 TI - Spectrum of efficacy of valproate in 55 patients with rapid-cycling bipolar disorder. AB - In order to explore valproate's spectrum of efficacy in rapid-cycling bipolar disorder, 55 patients underwent a prospective, open, 7.8-month trial designed to assess the drug's acute and prophylactic properties. Twenty patients received monotherapy, and 35 received combination therapy. Moderate to marked acute antidepressant responses were seen in 47% of the patients, prophylactic antidepressant responses in 76%, acute antimanic responses in 91%, prophylactic antimanic responses in 94%, acute responses in mixed states in 85%, and prophylactic responses in mixed states in 93%. Consistent with other anticonvulsant literature, these data suggest that valproate has marked antimanic and mixed state efficacy, but minimal to moderate antidepressant properties. PMID- 2107763 TI - Relapse following discontinuation of lithium maintenance therapy in adolescents with bipolar I illness: a naturalistic study. AB - The authors conducted an 18-month naturalistic prospective follow-up study of 37 adolescents whose bipolar I illness had been stabilized with lithium carbonate during inpatient hospitalization. Thirteen of the patients discontinued prophylactic lithium therapy shortly after discharge. The relapse rate of bipolar illness in these 13 patients was nearly three times higher than the rate in patients who continued lithium prophylaxis without interruption. Early relapse among lithium-treated patients was associated with a greater risk of relapsing again. The authors discuss the theoretical and clinical implications of these findings. PMID- 2107764 TI - Serious adverse effects of combining fluoxetine and tricyclic antidepressants. PMID- 2107765 TI - The quality of ambulatory care in Medicare health maintenance organizations. AB - The quality of ambulatory care received by Medicare recipients who enrolled in health maintenance organizations (HMOs) was compared to the care received by fee for-service (FFS) Medicare recipients, in a quasi-experimental, non-randomized design. Both samples were drawn from the four major geographic areas in the country, and included two types of HMO practices: staff/group models, and independent practice associations (IPAs). A panel of expert physicians developed criteria for evaluating ambulatory care, and medical record abstractions using these criteria were performed on 1,590 outpatient records: 777 FFS and 813 HMO (441 staff/group, 372 IPA). While individual items of medical histories and physical examinations were performed most often for staff/group HMO patients and least often in FFS patients, odds ratios (OR) for performance in staff/group HMO patients were particularly large for health maintenance items: tonometry (OR = 8.4), mammography (OR = 2.7), pelvic examination (OR = 5.3), rectal examination (OR = 2.9), fecal occult blood test (OR = 3.3). The results suggest that recommended elements of routine and preventive care are more likely to be performed for Medicare enrollees in staff/group HMOs than in FFS settings. PMID- 2107766 TI - Screening for chlamydial cervicitis in a sexually active university population. AB - Enzyme-linked immunoabsorbent assays to detect chlamydial cervicitis were performed on samples from 1,320 sexually active university women. Seventy-five (prevalence 5.7 percent) had positive tests. Demographic, history, symptom, and physical examination variables were insufficient to predict infection accurately. We conclude that screening during routine visits with this population is cost effective. PMID- 2107767 TI - Changes in antischistosomal drug usage patterns in rural Qalyubia, Egypt. AB - To investigate the usage of antischistosomal drugs in the Nile Delta, an antischistosomal drug history was obtained by interview from a sample of inhabitants of the villages of Halaba (1,024, or every 4th household) and Kharkania (505, or every 20th household), south-central Nile Delta. Only 3% and 0.4% of participants, respectively, in the 2 villages reported receiving antischistosomal drugs during the previous 4 years. Most villagers received oral compounds (praziquantel and niridazole), and the treatment regimen was completed by 95%. This study reveals changes in antischistosomal drug usage since a study 8 years earlier in the village of Halaba, when most of the drugs were injectable compounds. PMID- 2107768 TI - Leukocyte adherence to Schistosoma haematobium eggs from children. AB - The pattern of leukocyte adherence to voided Schistosoma haematobium eggs was compared in children 7-16 years old. A method enabling the measurement of the intensity of adherence was first developed by means of scanning electron microscopy, after which it was adapted for light microscopy. The intensity of adherence decreased from younger to older age groups. This result was unexpected, and has bearing on contemporary views on immunity to human schistosomiasis, particularly the blocking antibody theory. PMID- 2107769 TI - Dissociation of immunoregulatory function of blood monocytes from maturational state and expression of interleukin-1 in humans chronically infected with Schistosoma mansoni. AB - We investigated the immunoregulatory function and properties of monocytes in 54 S. mansoni infected Egyptians (40-3,840 S. mansoni eggs excreted per gram of stool) 13-35 years of age. Adherent cell-mediated suppression was found in 11 of 36 patients. Cytochemical studies and reactivity with monoclonal antibodies directed at differentiation markers failed to show alterations in the distribution or maturation of monocytes. Peripheral blood mononuclear cells (PBMC) from these individuals produced lower levels of interleukin-1 (IL-1) in response to bacterial lipopolysaccharide and Staphylococcus albus stimulation as compared to the other S. mansoni infected individuals. Overall, IL-1 production by PBMC stimulated with LPS or Staphylococcus albus was higher in infected individuals compared to uninfected controls and correlated with intensity of infection (r = 0.41, P = 0.002 for LPS; r = 0.45, P = 0.006 for S. albus). IL-1 expression by monocytes from individuals with heavy S. mansoni infection exceeded that of subjects with light infection. The intensity-related increase in IL-1 expression did not correlate with the maturational state or the immunoregulatory properties of the monocytes. PMID- 2107770 TI - Distribution of neutralizing antibodies to California and Bunyamwera serogroup viruses in horses and rodents in California. AB - Neutralization tests were done on sera from 141 horses from high elevation regions of California. Antibody prevalences to Jamestown Canyon, snowshoe hare, and California encephalitis viruses in the California serogroup and Northway virus in the Bunyamwera serogroup were 55%, 43%, 18%, and 46%, respectively. In 51 horses from rural low elevation regions, seroprevalences were 31%, 35%, 35%, and 37%, respectively. Twenty-four horses from a suburban lowland area were seronegative, except for a single horse with a low titer to snowshoe hare virus. Seroprevalence to Jamestown Canyon and snowshoe hare viruses was associated with increasing age. Only 2 of 177 rodents from the Sierra Nevada had antibodies to Northway virus; none had antibodies to Jamestown Canyon or snowshoe hare viruses. PMID- 2107771 TI - Nutritional support in surgical practice: Part II. AB - On admission, a group of high-risk patients who are potential candidates for surgery can be identified, in whom prompt initiation of preoperative enteral or parenteral nutrition may reduce postoperative morbidity and mortality irrespective of the nutritional status. Among these are patients with inflammatory bowel disease, gastrointestinal fistulas, and pancreatitis. Substantial nutritional support has little or no direct effect upon the pathogenesis of the disease, but the discontinuance of oral intake may well have a beneficial effect on the basic disease process. Thus, the provision of enteral or parenteral nutrition gives the patient an optimal opportunity to marshal host defenses in support of healing. In organ system failures, e.g., acute renal failure, liver failure, and pulmonary failure, appropriate nutritional support may assist the patient in coping with the abnormal intermediary metabolism resulting from such failure until satisfactory organ system function returns. From this review, it seems reasonably clear that the initially malnourished patient is less able to successfully withstand the adverse effects of vigorous therapy and/or severe illness than is the well-nourished individual. Hence, correction of malnutrition, either before initiating therapy or concomitant with the treatment, is very likely to be beneficial. PMID- 2107772 TI - Use of mannitol as a measure to prevent postoperative renal failure in patients with obstructive jaundice. PMID- 2107773 TI - Local application of EMLA and glyceryl trinitrate ointment before venepuncture. AB - One hundred unpremedicated fit day surgery patients aged between 27 and 68 years were allocated randomly into one of four groups and EMLA, glyceryl trinitrate, EMLA and glyceryl trinitrate or a placebo ointment was applied to the dorsum of a hand. The pain and ease of venepuncture were determined at induction of anaesthesia 60 minutes later. Pain scores were also reassessed 1-2 hours after operation. Lower pain scores and easier venepuncture occurred when EMLA and glyceryl trinitrate ointment was applied to the dorsum of the hand. PMID- 2107774 TI - Effect of combined infusion of nitroglycerin and nicardipine on femoral-to-radial arterial pressure gradient after cardiopulmonary bypass. AB - Nitrates and calcium channel blockers are frequently administered during cardiac surgery. We simultaneously measured femoral arterial pressure and radial arterial pressure to investigate whether nitrates, in conjunction with calcium channel blockers, would influence the central-to-peripheral arterial pressure gradient. Combined nitroglycerin and nicardipine infusion during cardiac surgery involving coronary artery bypass grafting or valve replacement resulted in a significant increase above baseline levels in the femoral-to-radial arterial pressure gradient at 60 min after cardiopulmonary bypass. In control patients there was no significant increase in the femoral-to-radial arterial pressure gradient at 60 min after completion of cardiopulmonary bypass. A subsequent study in patients given nitroglycerin and nicardipine identified that the difference in the systolic arterial pressure between femoral and radial arteries was observed 15, 60, and 120 min after completion of cardiopulmonary bypass. However, there was no difference in the mean arterial pressure between femoral and radial arteries throughout the same period. We conclude that combined infusion of nitroglycerin and nicardipine, a new calcium channel blocker, intensifies the magnitude and duration of the femoral-to-radial arterial pressure gradient after cardiopulmonary bypass. PMID- 2107775 TI - Extremity tourniquet deflation increases end-tidal PCO2. PMID- 2107776 TI - Cost of invasive monitoring: a yet unresolved issue. PMID- 2107777 TI - Comparison of the complement-fixation and agar gel immunodiffusion tests for diagnosis of subclinical bovine paratuberculosis. AB - The performance of the serum complement fixation (CF) test was compared with that of a serum agar gel immunodiffusion (AGID) test on 74 subclinically infected and 154 uninfected cattle in 6 commercial midwestern dairy herds with Mycobacterium paratuberculosis infection and on 30 cattle in a herd that was free of infection. Infection status of cattle within herds was established by performance of a series of 3 or more fecal cultures and of ileocecal lymph node cultures of culled cattle. In cattle with subclinical infection detected by culturing, the sensitivity estimates of the CF and AGID tests were 10.8% (3.6% SE) and 18.9% (4.5% SE), respectively. In the cattle classified as disease free, the specificity estimates of the CF and AGID tests were 97.4% (1.3% SE) and 99.4% (0.6% SE), respectively. Neither set of estimates was significantly different. Negative test results obtained with the use of either test in apparently normal cattle from suspect herds should be interpreted with caution because both tests suffer from low sensitivities in subclinically infected animals. However, the AGID test may be more useful in regulatory situations in which the CF test is currently used because the AGID test is easier to perform and to interpret. PMID- 2107778 TI - Effect of orally administered epidermal growth factor on the jejunal mucosa of weaned pigs. AB - The effect of ingested epidermal growth factor (EGF) on the small intestinal mucosa of conventionally weaned pigs was determined. At 21 days of age, 39 pigs were randomly distributed into suckling and weaned treatment groups that were administered 124 micrograms of EGF, 372 micrograms of EGF, or the dosing compound daily. Fecal water content was determined daily. On postweaning days 0, 3, 6, and 9, representative pigs from each group were euthanatized, and jejunal mucosa samples were collected for determination of villus-to-crypt ratio, total protein content, disaccharidase activities, and microbiological populations. At postweaning day 3, the 372-micrograms dose of EGF significantly (P less than or equal to 0.05) increased jejunal lactase and sucrase activities in the weaned pigs. Increased lactase activity was not greater than that of the suckling pig controls, whereas sucrase activity was significantly (P less than or equal to 0.05) higher than that of the suckling pig controls. Significant changes were not observed in villus-to-crypt ratio, mucosal protein content, or disaccharidase activities on other collection days. PMID- 2107779 TI - Single session panendoscopy. Indications and expectations for yield. AB - To assess the indications and yield of single session panendoscopy (SSPE), patients who underwent colonoscopy and esophagogastroduodenoscopy (EGD) at the same time were retrospectively reviewed. Endoscopy records and patient charts of 101 patients who underwent SSPE during a 45-month period were analyzed for demography, indication, and results. Average age was 72.9 years. Common indications were positive occult blood tests (74%), anemia (28%), altered bowel habits (15%), and iron deficiency (13%). Most frequent findings at colonoscopy included diverticulosis (47%), polyps (37%), hemorrhoids (28%), and arteriovenous (AV) malformations (13%). Nine cases of cancer were found, seven of which were right-sided. Colonoscopy was normal in 12 per cent. EGD findings include esophagitis (55%), hiatal hernia (47%), and gastritis (33%). Eleven per cent were normal. Occult blood loss is not predictive of either a positive or negative study. SSPE is a safe and specific approach; however, based on this study, colonoscopy is recommended as the initial study for occult blood loss with plans to proceed to EGD when the lower endoscopy is normal. Even when the colonoscopy suggests the etiology for occult blood loss, EGD will yield a significant number of treatable and unsuspected lesions. PMID- 2107780 TI - Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. AB - STUDY OBJECTIVE: To determine the efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) in primary pulmonary hypertension. DESIGN: Randomized trial with 8-week treatment periods and nonrandomized treatment for up to 18 months. SETTING: Four referral centers. PATIENTS: Sequential sample of 24 patients with primary pulmonary hypertension. Nineteen patients completed the study. Four patients died and one left the study because of adverse effects (pulmonary edema). INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pump at doses determined by acute responses during baseline catheterization in ten patients. Nine patients were treated with anticoagulants, oral vasodilators, and diuretics. MEASUREMENTS AND MAIN RESULTS: Starting with a baseline value for total pulmonary resistance of 21.6 units, there was a decrease of 7.9 units (95% CI, -13.1 to -2.2; P = 0.022) in the prostacyclin-treated group after 8 weeks; there was virtually no change in the conventional therapy group (from 20.6 to 20.4 units, not significant). Six of ten prostacyclin-treated patients who completed the 8-week study period had reductions in mean pulmonary artery pressure of greater than 10 mm Hg, whereas only one of nine in the conventional treatment group had a similar response (P = 0.057). Nine patients receiving prostacyclin for up to 18 months have persistent hemodynamic effects, although dose requirements have increased with time. Complications have been attributable to the drug delivery system. CONCLUSIONS: Prostacyclin produces substantial and sustained hemodynamic and symptomatic responses in severe primary pulmonary hypertension and may be useful in the management of some patients with this disease. PMID- 2107781 TI - Coronary thrombolysis: streptokinase or recombinant tissue-type plasminogen activator? AB - In patients with acute myocardial infarction, intravenous streptokinase therapy recanalizes 40% to 45% of occluded coronary arteries and reduces mortality by 25%. Recombinant tissue-type plasminogen activator (rt-PA) therapy is more potent for coronary arterial thrombolysis, producing both more rapid and more frequent (65% to 70%) reperfusion. Side effects (mainly reocclusion and bleeding) of streptokinase and rt-PA therapy are not markedly different. Whether the higher efficacy of rt-PA therapy will translate into a comparably larger reduction of morbidity and mortality remains to be determined in large comparative clinical trials. Both agents are available for clinical use. At present, the choice of agent for treating acute myocardial infarction must be based on consideration of the lower cost of streptokinase therapy compared with the established higher efficacy of rt-PA therapy for coronary recanalization. PMID- 2107782 TI - Tissue plasminogen activator and heparin dosage. PMID- 2107783 TI - [A review of four cases of Branhamella catarrhalis bacteremia in children]. AB - Branhamella catarrhalis was recovered from one blood culture each from three infants and one neonate admitted to the Trousseau Hospital (Paris) between 1986 and 1988. Clinical features included fever in every case, otitis in three cases, pneumonia in two cases, diarrhea in one case, and enterocolitis in one case. All the strains were beta-lactamase producers. Outcome was favorable in every case. The antimicrobial agent used was erythromycin in one case, amoxicillin in one case, and a third generation cephalosporin in two cases. We reviewed the pediatric literature for reports of Branhamella catarrhalis infections that seem more frequent or better detected than previously. The high prevalence of ampicillin-resistant strains is pointed out. PMID- 2107784 TI - [Comparative study of cibenzoline and flecainide administered via an intravenous route in reducing auricular arrhythmia]. AB - The efficacy of intravenous flecainide and cibenzoline acetate in the reduction of atrial rhythm disorders was compared in two groups of 30 patients. These arrhythmias are divided in 31 atrial fibrillation, 11 tachy-systoles, 18 atrial flutters. Parenteral administration of the anti-arrhythmic drug over a 24 hour period is preceded by a bolus injection of 1.5 mg/kg of flecainide acetate for group I, and a bolus of 1 mg/kg of cibenzoline for group II. The overall efficacy of the two molecules is comparable (53%) as well as the reduction of the atrial fibrillations (65% vs 57%). Flecainide acetate seems more effective in treating effectively atrial tachycardias (66.6% vs 40%), and cibenzoline is more effective in the treatment of atrial flutters (54% vs 14%). The functional, electrical and haemodynamic tolerance has always been good in both group, except in 2 patients, because of the indirect pro-arrhythmic effect of cibenzoline. We are concluding that the efficacy of both molecules is satisfactory and we advocate their use, as first intention, in recent and idiopathic atrial fibrillation; it seems that cibenzoline is more effective on ischemic cardiopathies and flecainide acetate is more effective on valvular cardiopathies. Nevertheless, the possible indirect pro arrhythmic effect, sometimes poorly tolerated in the first minutes following administration of the bolus, only on organized atrial rhythm disorder, leads us to advocate the prescription of these two drugs when attempts of transesophageal or endocardiac atrial stimulation have failed. PMID- 2107785 TI - Age-related changes in the human nigrostriatal dopaminergic system. AB - A deficiency of dopamine in the striatum may contribute to the decline in motor function associated with aging. We examined the effect of aging on the densities of the D1 and D2 dopamine receptors, their high-agonist affinity sites, and the dopamine uptake sites in postmortem human putamen (n = 32; age range, 19-88 years). With aging a steady decrease was seen in dopamine uptake sites (p less than 0.001), confirming previous morphometric and biochemical data of an age related loss of nigrostriatal axons. In contrast, the concentrations of the D1 and D2 dopamine receptors and their high-agonist affinity sites, which are believed to represent the functionally active receptors, were not affected by the aging process. These results may have implications for the pharmacological treatment of the age-related decline in motor function. PMID- 2107786 TI - Research innovations: a contradiction of terms? PMID- 2107787 TI - Key issues in the family research process: strategies for nurse researchers. AB - Family research has recently emerged as a critical area for nursing science. The distinctive nature of the family as a system of interacting persons raises special challenges for family nurse researchers. In this article conceptual and methodologic issues unique to family research are addressed within three phases of the research process. Strategies for family research are also suggested. Lastly, the article proposes directions for family nursing research. PMID- 2107788 TI - A feminist poststructuralist analysis of the knowledge of menopause. AB - The aim of this research innovation was to foster an understanding of women's experiences with menopause by exploring the interrelation between the knowledge in the scientific/medical discourses, both past and present, and the knowledge in the everyday discourses of a select sample of midlife women regarding the closure of menstrual life. The significance of this study is that it provides a social, historical, and cultural horizon from which to begin to understand the experiences of menopause. By developing an alternative knowledge of menopause, this research challenges the prevailing discourses of menopause, resists the way these discourses have solidified into what is accepted as truth, and makes visible the links among values, assumptions, research, and knowledge. PMID- 2107789 TI - Language as research data: application of computer content analysis in nursing research. AB - Statements from clients are valuable research data in nursing. Traditional analysis of such data can be labor intensive and difficult to code reliably or to adapt to group comparisons. The Minnesota Contextual Content Analysis, a computer assisted analysis program, offers a systematic approach to categorizing and reducing data and to interpreting manifest and latent meaning in linguistic communications. The text is used in entirety, and reliability of coding is ensured, even with great volumes of data and multiple variables. Social context of the communication and emphasized ideas are scored variables, allowing for statistical procedures to further refine the interpretation of meaning. This rigorous method can aid nurse researchers in using language as research data. PMID- 2107790 TI - Refining an emergent life-style-change theory through matrix analysis. AB - Matrix analysis is a methodologic tool used by researchers to systematically enter qualitative data into matrices and to simultaneously perform the complex integrative functions of data analysis and verification of findings. The article focuses on (1) the steps of qualitative data analysis that can be achieved by using matrix analysis, (2) the appropriate conditions for using matrix analysis, (3) the procedure for constructing a matrix, (4) the application of matrix analysis to a research problem that involved refining an emergent theory of the health life-style-change process, and (5) the use of matrix analysis to meet the criteria for trustworthiness of research findings. PMID- 2107791 TI - The use of ethology in clinical nursing research. AB - Although the pragmatic implications for observational research in nursing are profound, these techniques are underused. In this article the methods of ethology, or the systematic detailed study of behavior, and its application to clinical nursing research are described. The authors suggest that ethology may be used to explore behavior in cognitively impaired, elderly patients, psychiatric patients, and infants. The authors also suggest that ethology is suited for examining subconscious or transitory phenomena, such as pain responses, that are unsuited to self-report methods. PMID- 2107792 TI - A methodology for validating nursing diagnoses. AB - A methodologic approach consisting of four phases is proposed for validating nursing diagnoses. The sequential phases include use of the Delphi technique, magnitude estimation scaling, patient observation, and testing nursing interventions through clinical trials. The proposed methodologic approach is a strategy for researching the diagnosis and treatment of human responses to actual or potential health problems--the foundation for nursing practice. PMID- 2107793 TI - The hybrid model for concept development: its value for the study of therapeutic alliance. AB - Schwartz-Barcott and Kim's hybrid model is used as a research methodology for the development and analysis of the concept of therapeutic alliance. Empirical data gathered in a community health setting by field research techniques are used to compare, to contrast, and to rework existing definitions and related concepts from literature review. The resulting definitional refinement provides clear distinctions between the concepts of compliance and therapeutic alliance and assists in selection of appropriate nursing interventions supportive of clients' health goals. PMID- 2107794 TI - Size-selective grazing on bacteria by natural assemblages of estuarine flagellates and ciliates. AB - The small average cell size of in situ bacterioplankton, relative to cultured cells, has been suggested to be at least partly a result of selection of larger sized cells by bacterivorous protozoa. In this study, we determined the relative rates of uptake of fluorescence-labeled bacteria (FLB), of various cell sizes and cell types, by natural assemblages of flagellates and ciliates in estuarine water. Calculated clearance rates of bacterivorous flagellates had a highly significant, positive relationship with size of FLB, over a range of average biovolume of FLB of 0.03 to 0.08 microns3. Bacterial cell type or cell shape per se did not appear to affect flagellate clearance rates. The dominant size classes of flagellates which ingested all types of FLB were 3- to 4-microns cells. Ciliates also showed a general preference for larger-sized bacteria. However, ciliates ingested a gram-positive enteric bacterium and a marine bacterial isolate at higher rates than they did a similarly sized, gram-negative enteric bacterium or natural bacterioplankton, respectively. From the results of an experiment designed to test whether the addition of a preferentially grazed bacterial strain stimulated clearance rates of natural bacterioplankton FLB by the ciliates, we hypothesized that measured differences in rates of FLB uptake were due instead to differences in effective retention of bacteria by the ciliates. In general, clearance rates for different FLB varied by a factor of 2 to 4. Selective grazing by protozoa of larger bacterioplankton cells, which are generally the cells actively growing or dividing, may in part explain the small average cell size, low frequency of dividing cells, and low growth rates generally observed for assemblages of suspended bacteria. PMID- 2107795 TI - Pyrite oxidation by thermophilic archaebacteria. AB - Three species of thermophilic archaebacteria of the genera Sulfolobus (Sulfolobus acidocaldarius and S. solfataricus) and Acidianus (Acidianus brierleyi) were tested for their ability to oxidize pyrite and to grow autotrophically on pyrite, to explore their potential for use in coal desulfurization. Only A. brierleyi was able to oxidize and grow autotrophically on pyrite. Jarosite was formed during the pyrite oxidation, resulting in the precipitation of sulfate and iron. The medium composition affected the extent of jarosite formation. PMID- 2107796 TI - Kinetics of Pseudomonas aeruginosa adhesion to 304 and 316-L stainless steel: role of cell surface hydrophobicity. AB - Fifteen different isolates of Pseudomonas aeruginosa were used to study the kinetics of adhesion to 304 and 316-L stainless steel. Stainless steel plates were incubated with approximately 1.5 X 10(7) CFU/ml in 0.01 M phosphate-buffered saline (pH 7.4). After the plates were rinsed with the buffer, the number of adhering bacteria was determined by a bioluminescence assay. Measurable adhesion, even to the electropolished surfaces, occurred within 30 s. Bacterial cell surface hydrophobicity, as determined by the bacterial adherence to hydrocarbons test and the contact angle measurement test, was the major parameter influencing the adhesion rate constant for the first 30 min of adhesion. A parabolic relationship between the CAM values and the logarithm of the adhesion rate constants (In k) was established. No correlation between either the salt aggregation or the improved salt aggregation values and the bacterial adhesion rate constants could be found. Since there was no significant correlation between the bacterial electrophoretic mobilities and the In k values, the bacterial cell surface charge seemed of minor importance in the process of adhesion of P. aeruginosa to 304 and 316-L stainless steel. PMID- 2107797 TI - Neonatal pneumonia. AB - All babies admitted to the neonatal unit during a period of 41 months were prospectively studied to find out the incidence, aetiology, and outcome of neonatal pneumonia, and the value of routine cultures of endotracheal tubes. Pneumonia of early onset (before age 48 hours) occurred in 35 babies (incidence 1.79/1000 live births). In 20 (57%) it was caused by group B streptococci. Blood cultures showed the presence of organisms in 16 of the 35 (46%). There were 41 episodes of pneumonia of late onset in 39 babies. Thirty six of the 39 were preterm, and 34 were artificially ventilated (10% of all ventilated babies). Endotracheal tube colonisation had occurred in 94% of these, most commonly by Gram negative organisms and Staphylococcus epidermidis. In only one of seven cases with simultaneous bacteraemia was the same organism grown from cultures of the blood. After controlling for gestational age and duration of artificial ventilation there was no difference in the incidence or timing of endotracheal tube colonisation between babies who did and did not have pneumonia of late onset. Ten babies with pneumonia of early onset (29%) died; all were preterm infants. Only one death (2%) was associated with an episode of pneumonia of late onset. Routine surveillance cultures were not helpful in predicting and managing pneumonia of late onset. PMID- 2107798 TI - Ultraviolet radiation suppresses mouse-ear edema induced by topical application of arachidonic acid. AB - The effect of ultraviolet (UV) radiation on arachidonic acid (AA) cascade was examined using an in vivo model. Mouse ear lobes were painted with 1 mg AA, and the maximum response of ear swelling was measured 1 h after challenge. Arachidonic-acid-induced ear swelling was significantly suppressed by preexposure to topical psoralen plus noninflammatory doses of long-wave UV radiation (PUVA) or middle-wave UV (UVB) radiation. Ultraviolet radiation may interfere with AA pathways to suppress ear swelling since AA-induced ear swelling is considered to be mediated by metabolites derived from exogenous AA. The results may relate to the therapeutic mechanisms of UV radiation in psoriasis in which the eicosanoid cascade is involved. PMID- 2107799 TI - Isotype distribution of anticardiolipin antibodies in systemic lupus erythematosus: prospective analysis of a series of 100 patients. AB - A prospective study of IgG and IgM isotypes of anticardiolipin antibodies (aCL) in a series of 100 patients with systemic lupus erythematosus was carried out. To determine the normal range of both isotype titres a group of 100 normal control serum samples was studied and a log-normal distribution of IgG and IgM isotypes was found. The IgG anticardiolipin antibody serum was regarded as positive if a binding index greater than 2.85 (SD 3.77) was detected and a binding index greater than 4.07 (3.90) was defined as positive for IgM anticardiolipin antibody. Twenty four patients were positive for IgG aCL, 20 for IgM aCL, and 36 for IgG or IgM aCL, or both. IgG aCL were found to have a significant association with thrombosis and thrombocytopenia, and IgM aCL with haemolytic anaemia and neutropenia. Specificity and predictive value for these clinical manifestations increased at moderate and high anticardiolipin antibody titres. In addition, a significant association was found between aCL and the presence of lupus anticoagulant. Identification of these differences in the anticardiolipin antibody isotype associations may improve the clinical usefulness of these tests, and this study confirms the good specificity and predictive value of the anticardiolipin antibody titre for these clinical manifestations. PMID- 2107801 TI - Total decompression of the spinal cord for combined ossification of posterior longitudinal ligament and yellow ligament in the thoracic spine. AB - One of the causes of hyperostosis in the spinal canal, ossification of the posterior longitudinal ligament (OPLL) combined with ossification of the yellow ligament (OYL) in the thoracic spine, can result in serious myelopathy, leading to sandwich-type compression of the spinal cord from anterior and posterior. For such cases we devised a treatment of total decompression of the spinal cord and intervertebral body fusion. This operation consists of two steps. The first step is designed for posterior and lateral decompression of the spinal cord by removal of the OYL following wide laminectomy. The second step is removal of the OPLL anteriorly for anterior decompression, followed by interbody fusion. As the final procedure of the first step, two deep parallel gutters, covering the extent of the OPLL to be removed anteriorly, are drilled down from the rear into the vertebral body along both sides of the dura. This pre-treatment makes removal of the OPLL anteriorly during the second stage much easier, faster, and safer. This operation is lengthy and demanding. However, based on our experience so far, it appears to be a promising surgical procedure. PMID- 2107800 TI - Nonsteroid anti-inflammatory drugs prevent the recurrence of heterotopic ossification after excision. AB - The prophylactic effect of nonsteroid anti-inflammatory drugs on the recurrence of high-grade periarticular heterotopic ossification after resection was studied in ten patients operated on for loosening of one or both components of a cemented total hip prosthesis. These drugs, given at a standard dosage for 1-3 weeks after surgery, prevented the recurrence of heterotopic ossification. In some patients the range of motion of their joint increased following surgery, while it remained unaffected in the majority. At follow-up 2-5 years after surgery, all patients walked well and there were no clinical or radiographs signs of loosening of the prosthetic components. It is concluded that treatment with NSAIDs following resection of periarticular heterotopic ossification prevents recurrence. PMID- 2107803 TI - The pH-dependent conformational transition in glycogen phosphorylase b. The effect of carnosine and anserine on its activity. AB - The conformational transition of phosphorylase b which occurs upon pH change from 6.0 to 7.0 is linked to the pH-dependent activity regulation. Skeletal muscle dipeptides, carnosine and anserine, activate rabbit and bovine phosphorylase b at pH 6.5-6.0 and inhibit it at pH 6.5-7.0. The enzyme activation constant was found to be equal to 20 mM, and the inhibition constant corresponded to 22 mM for both carnosine and anserine. The data obtained suggest that glycogen phosphorylase b adopts different conformational states at pH 6.0 and 7.0. Evidence for the pH induced conformational transition of the enzyme was obtained using chemical modification of histidine residues. The change in the phosphorylase activity under effects of the dipeptides in the pH range of 7.0-6.0 may be due to their physiological role in muscle contraction. PMID- 2107802 TI - Immunological characterization of the Marin County strain of astrovirus. AB - Marin County virus (MCV) was isolated from a stool suspension and serially propagated in human embryonic kidney cell cultures. MCV particles in stool and cell-propagated virus stocks showed reactivity by immune electron microscopy (IEM) with rabbit antiserum to astrovirus type 5. MCV antigen was also detected in two MCV stool samples by enzyme immunoassay (EIA) with an astrovirus group specific monoclonal antibody. Acute and convalescent sera from 3 of 3 MCV infected patients showed seroconversion to cell-propagated MCV by EIA. Immunofluorescence of MCV propagated in cell culture showed positive reactivity with an astrovirus group specific monoclonal antibody and astrovirus type 5 antiserum, with some cross-reactivity with astrovirus type 1. Similar results were obtained with the prototype strain of astrovirus type 5. However, in plaque reduction assays, both the prototype astrovirus type 5 and MCV were neutralized by type 5 antiserum only. We conclude that MCV can be serially propagated by techniques used for previously described astroviruses and is serotypically an astrovirus type 5. PMID- 2107804 TI - Intestinal glycosyl-transferase activities. Nutritional regulation by a chemically-modified protein: methionyl-casein. AB - In order to estimate the effect of a chemically modified casein, glycosylation processes were studied in rats fed a diet containing this protein. Two groups of rats were fed either a methionyl-casein diet or a normal casein diet. The methionyl-casein was enriched in methionine by covalent linkage of this amino acid. The nutritional data (growth, protein intake...) were not modified by the diet. The microsomal N-acetylgalactosaminyl- and fucosyl-transferase activities were unaffected by the diet. On the contrary, the soluble fucosyl-transferase activity was enhanced and the activation of fucose transfer in cytosol from methionyl-casein-diet fed rats disappeared after enzyme purification by DEAE cellulose chromatography. The activation was not explained by changes in some interfering reactions (glycosyl-nucleotide pyrophosphatase, oxidase, protease activities). PMID- 2107805 TI - Effect of fructose on glycogen synthesis in the perfused rat liver. AB - The effect of fructose on glycogen synthesis was examined in the perfused liver of starved rats. With increasing fructose concentration in the perfusate, glycogen synthesis and the % a form of glycogen synthase increased to a maximum at 2 mM and then decreased, progressively. The glucose 6-P level increased with the increase in fructose concentration. On the other hand, the ATP content was unchanged at a concentration of 2 mM or less and decreased at 3 mM or more. We also showed that the stimulation of glycogen synthesis by fructose at a concentration of 2 mM or less was due to activation of glycogen synthase by accumulated glucose 6-P and that ATP depletion at a concentration of 3 mM or more caused an increase in phosphorylase a and a decrease in glycogen synthase activity even in the presence of a high concentration of glucose 6-P. PMID- 2107806 TI - Dissociation of immune responses to the SS-A (Ro) 52-kd and 60-kd polypeptides in systemic lupus erythematosus and Sjogren's syndrome. AB - The cellular RNA particle SS-A (Ro) is a target of autoimmune response in many patients with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). Recent immunologic, biochemical, and DNA cloning studies have shown that the SS-A particle consists of at least 2 polypeptide components, of 52 kd and 60 kd. Immunodiffusion analysis of 60 sera from patients with primary SS revealed 47 (78%) to be SS-A precipitin positive. Western blotting studies of the sera showed 3 groups of reactivities: 22 (47%) possessed autoantibodies against both the 60 kd and the 52-kd polypeptides, 19 (40%) reacted only with the 52-kd protein, and 6 (13%) were nonreactive in Western blots although positive in immunodiffusion. Fifty-one of 90 SLE sera (57%) were SS-A precipitin positive by immunodiffusion. In Western blots, 24 (47%) possessed antibodies against both the 60-kd and the 52 kd antigens, while 9 (18%) reacted only with the 60-kd protein. Eighteen (35%) were nonreactive by Western blot, although positive by immunodiffusion. Antibody to the 52-kd antigen without concomitant antibody to the 60-kd antigen was seen only in patients with primary SS, whereas antibody to the 60-kd antigen without concomitant antibody to the 52-kd antigen was seen only in SLE patients. Although antibodies to SS-A are detected in both SS and SLE, our findings show that there is dissociation of immune responses to the 2 component antigens of the particle, which may be evidence of different events initiating the autoimmune process in these diseases. PMID- 2107807 TI - Not only but also? Comments on "How does convulsive therapy work"? PMID- 2107808 TI - [Temporary designation of central hospitals for AIDS]. PMID- 2107809 TI - [Integrated nursing leadership]. PMID- 2107810 TI - [Disciplinary law or injustice for nurses?]. PMID- 2107811 TI - [The comfort of caring]. PMID- 2107812 TI - [Project Standard Nursing Care Plans. An interview with members of the project group]. PMID- 2107813 TI - [What are they doing to me?]. PMID- 2107814 TI - [Total hip surgery and patient information]. PMID- 2107815 TI - [Living with CARD, where do you learn that?]. PMID- 2107816 TI - [Don't leave the cancer patient's partner out in the cold!]. PMID- 2107817 TI - [From taboo to policy? (1) Homosexuality and the TvZ. An exploratory study: 1930 1990]. PMID- 2107818 TI - [The nurse with A diploma in district nursing. A transient phenomenon?]. PMID- 2107819 TI - [The Stinissen case for the last time? An analysis of the judgment by the Arnhem Court 10-31-'89]. PMID- 2107820 TI - [Attitude and AIDS. A survey among nurses]. PMID- 2107821 TI - [You can't stop at one lesson or information session]. PMID- 2107822 TI - [The emancipated patient--or: why I believe in dialogue]. PMID- 2107823 TI - [From taboo to policy? (2). Homosexuality and TvZ. An exploratorystudy: 1930 1990]. PMID- 2107824 TI - ["I continue to follow professionalization in The Netherlands closely". George Evers exchanges Maastricht for Louvain. Interview by Toine de Graaf and Aart Eliens]. PMID- 2107825 TI - [The formation of nursing instructors for HBO (Higher Professional Education)]. PMID- 2107826 TI - Independence of benzodiazepine and opiate action in the suppression of isolation distress in rat pups. AB - To determine whether benzodiazepines (BDZs) quiet isolation distress in 10-day old rat pups by causing a release of endogenous opioids, a blockade of the effects of chlordiazepoxide (CDP) by the opiate antagonist naltrexone (NLX) was sought. Nonsedating doses of morphine (MOR) (0.125 mg/kg) and CDP (2.0 mg/kg) were equally effective in reducing ultrasonic vocalizations and other indices of isolation distress. Appropriate blocking agents NLX, (0.5 mg/kg) against MOR and Ro 15-1788 (4.0 mg/kg) against CDP returned distress measures to levels of saline treated rat pups. However, NLX failed to reverse the quieting effects of CDP. If CDP potentiates endogenous opioid release, then NLX should block the CDP effect. A higher dose of CDP did not reveal a release of endogenous opioids, and a higher dose of NLX did not antagonize CDP. The quieting effects of BDZs on isolation distress do not appear to be mediated by the opiate system. PMID- 2107827 TI - Induction of experimental chronic Pseudomonas aeruginosa lung infection with P. aeruginosa entrapped in alginate microspheres. AB - Alginate-producing, mucoid P. aeruginosa is frequently found in the lungs of patients with cystic fibrosis (CF), where it causes a chronic infection. The importance of alginate in the pathogenesis was demonstrated by the ability to establish chronic P. aeruginosa lung infection in rats if P. aeruginosa entrapped in minute alginate-beads were inoculated transtracheally. Alginate beads containing P. aeruginosa were formed by nebulizing a suspension of seaweed sodium alginate and P. aeruginosa into a calcium solution. The alginate bead method of establishing infection was compared to an agar-bead method and proved to be quantitatively similar after 4 weeks. The ability of the two methods to induce formation of precipitins, IgA and IgG antibodies against P. aeruginosa antigens, including outer membrane proteins, flagella, exoenzymes and alginate, was assessed by crossed immunoelectrophoresis, enzyme-linked immunosorbent assay and immunoblotting. The two methods of inducing infection were comparable and infected rats had significantly higher antibody response than rats inoculated with sterile beads. We suggest that the alginate bead model closely resembles the later stages of CF-lung infection and that it offers the theoretical advantage of using a substance which is chemically similar to the alginate produced in vivo by P. aeruginosa. PMID- 2107828 TI - Free haemagglutinin in inactivated whole virus influenza vaccines. AB - While studying the haemagglutinin content of whole virus inactivated influenza vaccines by the single radial diffusion test and quantitative electron microscopy, it was found that not all haemagglutinin measured by single radial diffusion was bound to virions, a part of it being in a free state. The influence of unbound haemagglutinin on the immunogenicity of whole virus inactivated influenza vaccine is discussed. In addition, the use of single radial diffusion for the assessment of unbound haemagglutinin is suggested. PMID- 2107829 TI - The International Standard for Netilmicin. AB - An International Standard for Netilmicin has been established on the basis of a collaborative assay. There were five participating laboratories in five countries. The activity of the contents of each ampoule of the International Standard for Netilmicin is defined as 4810 IU of netilmicin. PMID- 2107830 TI - Feeding preterm infants with L-carnitine supplemented formula. AB - A total of 29 preterm infants maintained on mixed enteral nutrition (50% pooled human milk, 50% formula daily) were studied over a 15 days period. 16 of them received L-carnitine supplemented formula during the first seven consecutive days (600 nmol/ml, as added supplement), 13 infants served as controls. In response to enhanced dietary intake, the plasma levels and urinary excretion rates of carnitines were increased by the 7th day of study. The plasma carnitines then returned to the initial values, whilst the urinary excretion remained elevated at the 14th day of study. The elevated daily urinary excretion of carnitines was accompanied by increased clearance and decreased relative reabsorption rates in the supplemented group. In the control group the plasma carnitine levels remained unchanged throughout the observations, while the daily excretion of free carnitine decreased by the end of the study. In the supplemented group statistically significant decrease was found in the daily excreted ammonia and urea with a decrease of plasma alanine and glutamine levels by the 7th day of study. The plasma levels of beta-hydroxybutyrate, glucose and creatinine remained unchanged in both groups. PMID- 2107831 TI - Failure of influenza vaccine to prevent two successive outbreaks of influenza A H1N1 in a school community. AB - Forty nine of the 149 boys (33%) at a preparatory school fell ill at the beginning of the autumn term 1986 with symptoms of influenza. One hundred and eighty two of the 470 pupils (39%) in the senior part of the same school had similar symptoms of influenza at the beginning of the spring term 1987. A new variant of influenza A H1N1 virus was isolated from both outbreaks and shown to be antigenically similar to A/Taiwan/1/86. The attack rate among pupils who had previously received trivalent influenza vaccine containing A/Chile/1/83 H1N1 antigen was not significantly different from the rate among those who had never been vaccinated. It is concluded that annual vaccination of all boarding school pupils may be inappropriate. PMID- 2107832 TI - Patient choice in a practice with men and women general practitioners. AB - This study investigated the distribution of workload between men and women doctors in a south London practice. Of 909 attending patients aged 15 years and over, 611 were women and 48% of these consulted a woman doctor. In comparison, only 27% of the 298 men consulted a woman doctor. Twenty nine per cent of the 105 women who gave a reason for choosing a woman doctor said they had done so because of her sex. Multiple logistic regression was used to assess the relative importance of having a general preference for a woman doctor or of consulting about a problem related to sex in predicting the likelihood of a woman consulting a woman doctor. This showed that preference was 2.3 times as important as problem type in predicting this. This suggests that woman's demand for women doctors in general practice extends beyond family planning and well woman clinics. The implications of this for practice organization are discussed. PMID- 2107833 TI - Inviting infrequent attenders to attend for a health check: costs and benefits. AB - A total of 114 patients who had not attended their general practitioner in the previous three years were identified by searching a sample of 1488 records (12.8% of the practice list). An invitation for a health check was sent, in keeping with the requirements of the new general practitioner contract. Seventeen out of 94 patients invited (18%) attended. Surgery staff spent 28 hours and the practice doctors spent 15 hours on arranging and carrying out the investigation. The group responding to the invitation were in general healthy; the only new finding of remediable disease was mild hypertension in one man. The smoking rate and alcohol consumption rate were low. Of 13 patients who needed tetanus immunization, five refused it and five failed to return. All three women who were overdue for a cervical smear failed to return to have it done. It is concluded that screening infrequent attenders is not an efficient use of medical time. PMID- 2107834 TI - Telephone advice for out of hours calls in general practice. AB - Telephone advice in out of hours general practice consultations has been infrequently described in the United Kingdom. Data from 13 general practices (77 doctors) in north London were collected over four-week periods. Of the 970 calls recorded, 86% were managed directly by the practice, and 14% by a deputizing service. The percentage of calls managed by telephone advice varied from 5% to 57% (mean 37%). Use of deputies increased at night, but general practitioners remaining on call maintained their telephone advice rates. In all but one practice trainees also gave telephone advice, but the overall proportion of calls managed by trainees (33%) was lower than that of principals (48%). Children and adults under 60 years, more frequently received telephone advice than elderly patients, as did patients noted by the general practitioners as habitual callers compared with other patients. PMID- 2107835 TI - Laboratory medicine in primary health care. PMID- 2107836 TI - Problems in using the hospital anxiety and depression scale for screening patients in general practice. AB - A study was made of the feasibility of screening general practice patients for anxiety and depression using the hospital anxiety and depression scale. A group of consecutive patients aged 18 years and over completed the questionnaire at the surgery and an age and sex matched sample were sent questionnaires by post; 94 patients (84%) returned the postal questionnaire. A further group of 170 consecutive patients coming for consultation were recruited. Using a threshold score of eight and over, 51% of patients screened by post were probable 'cases' of psychiatric disorder and using a score of 11 and over, 28% were 'cases'. These proportions were similar for patients screened when attending the surgery. The findings are discussed in the context of well-person screening, and a strategy for follow-up of probable cases is put forward. PMID- 2107837 TI - Psychological sequelae of sexual abuse in childhood. AB - A questionnaire survey was carried out in one practice to determine the relationship between sexual abuse in childhood and subsequent psychological morbidity. Out of 418 women who replied (62% response rate), 60 (14%) admitted experiencing some form of sexual abuse as a child. Twenty of these (33%) were found to have a record of some form of psychological problem in adult life, compared with 14% of a sample of the non-abused respondents and 20% of the non respondents. In particular, 54% of 13 women who had experienced oral, genital or anal penetration or attempted penetration had psychological morbidity recorded. There was no relationship, however, between sexual abuse and psychosexual or marital problems in later life. PMID- 2107838 TI - Near patient testing in general practice: a review. AB - Until recently, technological advances in general practice have generally been thought of as the applications of microcomputers in practice organization and record keeping. Advances in miniaturization and versatility of diagnostic technology will have a similarly large impact on the way general practitioners practice medicine in the next decade. This article reviews some of the newer tests that are already available to general practitioners, particularly in diagnostic biochemistry and microbiology. Preliminary evaluative work and research studies in general practice are also described. PMID- 2107839 TI - Patient management of post-viral fatigue syndrome. AB - A case definition for post-viral fatigue syndrome is proposed within which various subgroups of patients exist. Any one treatment may not apply to all the subgroups. In particular, patients' experiences do not show that avoidance of exercise is maladaptive. It is proposed that the recently ill often try to exercise to fitness whereas the chronically ill have learnt to avoid exercise. Recovery is more likely to be achieved if patients learn about their illness and do not exhaust their available energy. PMID- 2107840 TI - James Mackenzie lecture 1989. Reactive and proactive care: a crisis. PMID- 2107841 TI - Pre-hospital management of infantile gastroenteritis. PMID- 2107842 TI - No endocervical cells. PMID- 2107843 TI - Health care in deprived areas. PMID- 2107844 TI - Women's experiences of miscarriage. PMID- 2107845 TI - Effect of small group education on the outcome of chronic asthma. PMID- 2107846 TI - Foreign body inhalation: a danger of metered dose inhalers. PMID- 2107847 TI - Promoting rational therapeutics: the Swedish guidelines and a UK response. PMID- 2107848 TI - Supply of medical and surgical appliances: is a new approach needed? PMID- 2107849 TI - Defaulters in general practice: reasons for default and patterns of attendance. AB - A series of 40 patients in general practice who failed to attend for their appointments were studied to look at their patterns of attendance over the previous five years, together with their reasons for default. The group not only defaulted more often than a group of age and sex matched controls but made significantly more visits to the surgery. Seventeen of the patients increased their default rate as their attendance rate increased over the five year period. The main reasons patients gave for defaulting on the occasion studied were: feeling too ill to attend (eight patients), resolution of symptoms (six) or forgotten/confused appointment time (seven). Four patients were thought by the general practitioner to need a home visit, two of whom were suffering from depression. Further research is needed to define those who would be expected to need a visit. PMID- 2107850 TI - Comparing trainer and trainee referral rates: implications for education and allocation of resources. AB - Referral rates and urgency of referral to hospital by six pairs of trainers and trainees were compared over one month in 1986. From 5846 consultations, 327 resulted in referral to hospital. Overall, the referral rates was low at 5.6 per 100 consultations; however, there was considerable variation in individual referral rates with trainees tending to follow their trainer's referral patterns, despite statistical adjustment for sharing the same practice. This paper critically examines the wisdom of using general practitioner referral rates for the purpose of resource allocation and education. PMID- 2107851 TI - Organization of care for diabetic patients in general practice: influence on hospital admissions. AB - The aim of this study was to determine whether there is a relationship between the structure of care for diabetes in general practice and the corresponding admission rates for diabetic patients to hospital. A questionnaire was sent to 350 group or single handed practices in the Oxford region and a retrospective analysis was made of admission rates using hospital activity analysis. Admission rates were adjusted for the age structure of the practices. The degree of organization of care was determined by drawing up a composite score from the answers to the questionnaire and comparing practices with few, average and many facilities. There was a significant trend in the rates of admission across the groups of practices: those with few facilities made 16.2 admissions per 10,000 population over two years, those with average facilities 13.8 admissions, and those with many facilities 14.0 admissions (chi-squared trend = 6.88, 1 df, P less than 0.01). These findings support the hypothesis that organized general practice care reduces the rate of hospital admissions, although there are many other influences on the admission rate from any one practice. PMID- 2107853 TI - Referrals to a hearing aid clinic: scope for improvement. AB - This study followed on from a recent national publicity campaign aiming to get earlier provision of hearing aids for elderly people, improve both patient and general practitioner awareness of hearing impairments and increase knowledge of alternative environmental aids among sufferers. The study intended to examine present patterns of patient presentation and general practitioner management within a major Scottish city. A random sample of patients over the age of 55 years referred to a hearing aid clinic were questioned on the nature of their hearing difficulty. Patients who attended their general practitioner at the suggestion of a relative were less likely to be referred at their initial visit and significantly less likely to have had their ears syringed than those who were self-motivated. Respondents had little knowledge of alternatives to hearing aids, although these are relevant to the disability experienced by the majority of these subjects. PMID- 2107852 TI - Outcome of referrals by optometrists to general practitioners: an 18 month study in one practice. AB - All general ophthalmic services forms (GOS18) received by one practice over an 18 month period were analysed and the patient outcome after two years noted from the practice records. Sixty one forms were collected. Fifty patients (82%) were referred by the general practitioners to the local eye hospital. Among the 45 patients that have so far been seen by an ophthalmologist, 22 (49%) were diagnosed as having cataracts, eight (18%) macular degeneration and two (4%) glaucoma. Thirteen patients (29%) were found to have normal eyes. Nine of the 61 patients (15%) were not referred to an ophthalmologist and two patients (3%) were already under review at the eye hospital. It is concluded that some referrals to ophthalmologists might be avoided if general practitioners received improved training in ophthalmology, However, general practitioners remain an effective filter in the referral system between optometrists and ophthalmologists. PMID- 2107854 TI - The Vale of Leven health promotion project. AB - A two stage health promotion programme is in progress in the Vale of Leven in Dunbartonshire. The first stage has been completed within a local factory (Polaroid UK Limited), the largest private employer in the district. A total of 1205 employees, representing 87% of the workforce, took part in the programme and were initially screened for coronary artery risk factors. Blood pressure, serum cholesterol, body composition and aerobic fitness were measured and smoking habits determined. Aspects of lifestyle were assessed by questionnaire. All employees whose initial cholesterol concentration was greater than 6.5 mM were given simple dietary advice and their cholesterol concentration thereafter remeasured. Eighty-two per cent of these men and 72% of these women succeeded in reducing their cholesterol, the men by a mean of 1.3 mM, the women by a mean of 0.7 mM. The health initiatives undertaken within the factory at the same time as screening are also described in this paper. PMID- 2107855 TI - Microhaematuria in general practice: is urine microscopy misleading? AB - During a health centre screening programme for men aged 60 years and over, the urinary dipstick results of 58 patients found to have microscopic haematuria were compared with the results of immediate microscopy at the health centre and routine microscopy by a hospital laboratory. There was agreement between a positive dipstick test for haematuria and the presence of red cells at routine microscopy reported by the hospital laboratory in only 18 cases (31%). Routine urine microscopy results requested from general practice should not be taken as the criterion for deciding whether further investigation is needed in cases of microscopic haematuria. PMID- 2107856 TI - Lyme disease: a review. AB - In the last decade, Lyme borreliosis has emerged as a complex new infection whose distribution is worldwide. The multisystem disorder, which primarily affects the skin, joints, heart and nervous system at different stages, is caused by the tick borne spirochaete Borrelia burgdorferi. After the first weeks of infection almost all patients have a positive antibody response to the spirochaete and serological determinations are currently the most practical laboratory aid in diagnosis. Treatment with appropriate antibiotics is usually curative. PMID- 2107857 TI - Standards in general practice: the quality initiative revisited. PMID- 2107858 TI - Service families: a new perspective for the general practitioner. AB - The psychological problems among the dependents of armed servicemen presenting to general practitioners are discussed, with particular emphasis on how the peculiarities of service life contribute to their aetiology and presentation. Within the UK, primary health care for service dependents is increasingly being provided by National Health Service general practitioners who have no knowledge of service life. An understanding of this minority group with its different lifestyle and subculture is important for management of these disorders. PMID- 2107859 TI - Arthritis in inner city general practices. PMID- 2107860 TI - Management of post-viral fatigue syndrome. PMID- 2107861 TI - Incidence of pelvic inflammatory disease. PMID- 2107862 TI - The spagyric art. PMID- 2107863 TI - Optimal value of filling pressure in the right side of the heart in acute right ventricular infarction. AB - Haemodynamic monitoring was performed within the first 48 hours after the onset of symptoms in basal conditions, during volume loading, and during infusion of glyceryl trinitrate in 41 patients who fulfilled the diagnostic electrocardiographic and haemodynamic criteria of right ventricular infarction. In most patients an increase of mean right atrial pressure up to 10-14 mm Hg was followed by an increase in right ventricular stroke work index. But raising the mean right atrial pressure above 14 mm Hg was almost always accompanied by a reduction in right ventricular stroke work index. When the mean right atrial pressure was reduced by intravenous glyceryl trinitrate to less than 14 mm Hg the right ventricular stroke index increased. The same response was seen with cardiac and stroke index. The mean (SD) values of optimal right atrial and pulmonary capillary pressures were 11.7 (2.1) and 16.5 (2.7) mm Hg respectively. Thus cardiac and stroke index increased and the right ventricle reached its maximum stroke work index when the filling pressure was 10-14 mm Hg. These values may be regarded as the optimal level of right ventricular filling pressure in patients with right ventricular infarction. PMID- 2107864 TI - Dimethylthiourea, a hydroxyl radical scavenger, impedes the inactivation of methionine synthase by nitrous oxide in mice. AB - Dimethylthiourea (DMTU), a potent scavenger of hydroxyl radicals, was studied to see if it attenuated the inactivation of methionine synthase produced by nitrous oxide in mice. Mice were given i.p. injections of DMTU 0.5-4.0 mg g-1 or saline and, 1 h after injection, were exposed to 66% nitrous oxide in oxygen for periods of 0.5-8 h. At given times after nitrous oxide exposure, higher methionine synthase activities were found in the livers, kidneys and brains of mice injected with DMTU than in the saline-injected animals. These higher methionine synthase activities in the DMTU-treated animals represented a delay in the enzyme inactivation produced by nitrous oxide, as the difference in activities between the DMTU-injected and saline-injected mice decreased with increasing duration of exposure to nitrous oxide. Greater differences in methionine synthase activities between the DMTU- and saline-injected animals were observed with increasing doses of DMTU. The rate of enzyme inactivation following exposure to nitrous oxide was greater in liver and least in brain, and the difference in activities between the two groups varied with the organ examined. DMTU exhibited its greatest effect in the kidney, where methionine synthase activities were nearly doubled in the DMTU 2.0 mg g-1-injected compared with the saline-injected mice after 1-h exposure to 66% nitrous oxide. Following a marked inactivation of methionine synthase by exposing mice to 66% nitrous oxide for 4 h, injection of DMTU 2.0 mg g-1 at the end of exposure to nitrous oxide did not enhance, but impaired, the recovery of enzyme activity. The findings are consistent with the hypothesis that nitrous oxide combines with the vitamin B12 molecule of methionine synthase to form a hydroxyl radical that reacts with an inactivates the enzyme, and that DMTU slows this inactivation by scavenging hydroxyl radicals. PMID- 2107865 TI - Early detection of "rebreathing" in afferent and efferent reservoir breathing systems using capnography. AB - Capnography was used to determine the onset of rebreathing in afferent (AR) and efferent (ER) reservoir breathing systems in a spontaneous ventilation lung model. In the case of the Lack and enclosed AR systems, the best sampling site was found to be in the exhaust limb of the systems, 5 cm from the Y connector. For the Magill system, fitted with a hooded scavenging valve, the best site was deep inside the hooded valve. In contrast, the best sampling site in an ER system (e.g. Bain system) was in the tracheal tube. For AR systems, the loss of a fresh gas elimination pattern (carbon dioxide trace failing to reach zero) was shown to occur at the onset of rebreathing. As the sampling site was moved distally into the exhaust limb, the same pattern was seen at greater flow rates--that is, before rebreathing was actually occurring. When sampling was within the tracheal tube, using ER systems, a typical "rebreathing wave" occurred at the onset of established rebreathing. PMID- 2107866 TI - Pro-inflammatory mediators induce sustained release of prostaglandin E2 from human dermal microvascular endothelial cells. AB - The vasodilator prostaglandin E2 has been proposed as a mediator of erythema in a variety of cutaneous inflammatory reactions and prostacyclin levels have been found to be elevated in ultraviolet induced erythema. Human recombinant interleukin 1 alpha and lipopolysaccharide induced a concentration- and time dependent release of prostaglandin E2, but not prostacyclin, from cultured neonatal and adult human dermal microvascular endothelial cells. Prostaglandin E2 was measurable at 2 h after stimulation with 1 U/ml interleukin 1 alpha, levels increased rapidly up to 6 h and more slowly up to 24 h. Lipopolysaccharide (20 micrograms/ml) induced measurable release of prostaglandin E2 between 2 and 4 h after stimulation and release continued up to 24 h when incubation was terminated. With both agonists, release of prostaglandin E2 was inhibited by indomethacin and significantly reduced by cycloheximide. The sensitivity and magnitude of responses of the cutaneous endothelial cells to these pro inflammatory stimuli appeared to be dependent on their derivation. PMID- 2107867 TI - Are ACA and Scl 70 antibodies mutually exclusive? AB - Serological studies using indirect immunofluorescence, double immunodiffusion and immunoblot with recombinant Topo I and kinetochore antigens were performed in 180 patients with systemic scleroderma. In the sera of 10 patients, we found coexisting ACA and Scl 70 antibodies, and this was confirmed by all three methods. The relationship between the coexistence of these antibodies and the clinical features of the disease is not clear, although in all these cases there was pronounced vascular involvement. PMID- 2107868 TI - Spontaneous NBT reduction by monocytes as a marker of disease activity in children with histiocytosis. AB - In an attempt to define a biological marker of monocyte hyperactivation in the course of infantile histiocytosis, the spontaneous nitroblue tetrazolium (NBT) reduction assay was applied to monocytes from 13 children with Langerhans cell histiocytosis (LCH), familial haemophagocytic lymphohistiocytosis (FHL), juvenile xanthogranuloma or malignant histiocytosis. Significant increase in NBT reduction was observed in the patients with both active LCH and FHL in comparison with control subjects, who were either healthy or affected by different conditions. A close relationship between spontaneous reduction rate and clinical condition of the patients was evident in patients tested at diagnosis, during remission and during the course of disease reactivation. Interleukin-1 (IL-1) production by monocytes was also evaluated: the patients with LCH and FHL displayed a significant increase in in vitro IL-1 production by lipopolysaccharide-stimulated monocytes. In our experience the spontaneous NBT reduction assay was a sensitive, quite specific, low-cost and reproducible test for the evaluation of children with histiocytosis. Useful information may be obtained at diagnosis but also during the clinical course of disease by using this marker of monocyte spontaneous activation. PMID- 2107869 TI - Metabolism of maltitol by conventional rats and mice and germ-free mice, and comparative digestibility between maltitol and sorbitol in germ-free mice. AB - The metabolism of maltitol (4-alpha-D-glucosylsorbitol) was assessed in fasting conventional (C) rats, C mice and germ-free (GF) mice, using [U-14C]maltitol. The radiorespirometric patterns of 14CO2 collected for 48 h after the administration of labelled maltitol were characterized by a constant rate of 14CO2 production lasting 4 h for both C rats and mice. The pattern for the GF mice showed a peak at the second hour followed immediately by a slow decrease. The percentage recovery of 14CO2 was significantly lower for the GF mice (59%) compared with C animals (72-74%). Urine, faeces and intestinal contents after 48 h totalled 19% of the administered radioactivity in the C rats and mice and 39% in the GF mice. The digestibility of maltitol and the absorption of sorbitol in GF mice was also assessed. The caecum and small intestine of GF mice, 3 h after administration of equimolar quantities of maltitol (140 mg/kg body-weight) or sorbitol (70 mg/kg body-weight), contained 39 and 51% of the ingested dose respectively, present mostly in the caecum as sorbitol. The alpha-glucosidase (maltase) (EC3.2.1.20) activity of the small intestine was appreciably higher (1.5-1.7 times) in the GF mice than in the C mice. These results suggest that the enzymic activities in the small intestine of mice and rats are sufficient to hydrolyse maltitol extensively. Consequently, the slow absorption of sorbitol seems to be an important factor limiting the overall assimilation of maltitol in the small intestine. PMID- 2107870 TI - Prevention of thromboxane B2-induced hepatocyte plasma membrane bleb formation by certain prostaglandins and a proteinase inhibitor. AB - Isolated hepatocytes incubated in the presence of thromboxane B2 developed many plasma membrane blebs which are a characteristic feature of toxic or ischaemic cell injury. When hepatocytes were incubated in the presence of both thromboxane B2 and the non-lysosomal proteinase inhibitor, leupeptin, were also well protected from the formation of blebs. This implies that thromboxane B2 is able to activate non-lysosomal proteinases which appear to attack certain cytoskeletal proteins. The data presented are consistent with thromboxane B2 acting as an intermediary in a proposed mechanism of cell injury and death in which elevated cytosolic free Ca2+ levels activate phospholipase A2 and the arachidonic acid cascade. PMID- 2107871 TI - Influence of duodenal secretions and its components on release and activities of human brush-border enzymes. AB - The in vitro effects of human duodenal secretions and various combinations of its components on activity and release of enzymes from the human brush border were examined. Sucrase retained activity for 90 min in duodenal secretions, and maltase was almost as stable; lactase lost activity rapidly and alkaline phosphatase was of intermediate stability. Inactivation of lactase could only be partly (50%) attributed to luminal proteases, bile salts and phospholipids played no role. Rate of release of an enzyme from the brush border bore no relationship to its rate of inactivation. When individual proteases were studied, elastase was the most potent for releasing disaccharidases from the brush border; trypsin was ineffective alone but augmented the effect of elastase. Sucrase and maltase were activated by proteolytic release, but activation was abolished by simultaneous exposure of brush borders to bile salts. Lactase was released and rapidly inactivated by proteinases, while alkaline phosphatase appeared to be inactivated without significant release. These results show that there are significant interactions between luminal factors which have been inapparent when studying them in isolation. Loss of functionally useful enzyme does not follow release of sucrase or maltase from the brush border into the lumen but does follow release of lactase. Study of the susceptibility of lactase to inactivation by luminal factors in the various forms of lactose intolerance is warranted. PMID- 2107872 TI - Beta-D-glycosidase activities of Humicola grisea: biochemical and kinetic characterization of a multifunctional enzyme. AB - A beta-D-glycosidase activity was purified from mycelium of Humicola grisea var. thermoidea grown on avicel as the main carbon source. The purified enzyme was a glycoprotein and migrated as a single polypeptide band on polyacrylamide gel electrophoresis under native or denaturing conditions. The apparent molecular weight of the enzyme was estimated to be 55 kDa by gel filtration and SDS-PAGE. The enzyme was active against o-nitrophenyl beta-D-galactoside; p-nitrophenyl beta-D-glucoside, p-nitrophenyl beta-D-fucoside, lactose and cellobiose, PNP fucoside (synthetic substrate) and cellobiose (natural substrate) being the best utilized. A comparison of the properties of beta-D-galactosidase, beta-D glucosidase and beta-D-fucosidase showed that three activities exhibited similar pH and temperature optima and the same thermostability. The hydrolysis rate of substrate mixtures suggests that the enzyme possesses a common catalytic site for all the substrates assayed. PMID- 2107873 TI - Activation of mammalian tyrosinase by ferrous ions. AB - Kinetic experiments are reported showing that mammalian tyrosinase from B16 mouse melanoma is significantly activated by catalytic amounts of ferrous ions. Monitoring of tyrosine oxidation by both dopachrome formation and oxygen consumption showed that ferrous ions at micromolar concentrations induce a marked enzymatic activity with 0.01 U/ml of highly purified tyrosinase, whereas no detectable reaction occurs in the absence of metal over a sufficiently prolonged period of time. The extent of the activating effect, which is specific for the reduced form of iron, is proportional to the concentration of the added metal with a typical saturation profile, no further effect being observed beyond a threshold value. Changing the buffer system from phosphate to hepes or tris results in a marked decrease of the Fe2(+)-induced activation. Scavengers of active oxygen species, such as superoxide dismutase, catalase, formate and mannitol have no detectable effect on the tyrosinase activity. These results are accounted for in terms of an activation mechanism involving reduction of the cupric ions at the active site of the resting enzyme. PMID- 2107874 TI - Effect of the antiepileptic drug sodium valproate on glutamine and glutamate metabolism in isolated human kidney tubules. AB - We studied the effects of sodium valproate, a widely used antiepileptic drug and a hyperammonemic agent, on L-[1-14C]glutamine and L-[1-14C]glutamate metabolism in isolated human kidney-cortex tubules. Valproate markedly stimulated glutamine removal as well as the formation of ammonia, 14CO2, pyruvate, lactate and alanine, but it inhibited glucose synthesis; the increase in ammonia formation was explained by a stimulation by valproate mainly of flux through glutaminase (EC 3.5.1.2) and to a much lesser extent of flux through glutamate dehydrogenase (EC 1.4.1.3). By contrast, valproate did not stimulate glutamate removal or ammonia formation, suggesting that the increase in flux through glutamate dehydrogenase observed with glutamine as substrate was secondary to the increase in flux through glutaminase. Accumulation of pyruvate, alanine and lactate in the presence of valproate was less from glutamate than from glutamine. Inhibition by aminooxyacetate of accumulation of alanine from glutamine caused by valproate did not prevent the acceleration of glutamine utilization and the subsequent stimulation of ammonia formation. It is concluded from these data, which are the first concerning the in vitro metabolism of glutamine and glutamate in human kidney-cortex tubules, that the stimulatory effect of valproate is primarily exerted at the level of glutaminase in human renal cortex. PMID- 2107875 TI - Kinetic mechanism of beta-glucosidase from Trichoderma reesei QM 9414. AB - beta-Glucosidase is a key enzyme in the hydrolysis of cellulose to D-glucose. beta-Glucosidase was purified from cultures of Trichoderma reesei QM 9414 grown on wheat straw as carbon source. The enzyme hydrolyzed cellobiose and aryl beta glucosides. The double-reciprocal plots of initial velocity vs. substrate concentration showed substrate inhibition with cellobiose and salicin. However, when p-nitrophenyl beta-D-glucopyranoside was the substrate no inhibition was observed. The corresponding kinetic parameters were: K = 1.09 +/- 0.2 mM and V = 2.09 +/- 0.52 mumol.min-1.mg-1 for salicin; K = 1.22 +/- 0.3 mM and V = 1.14 +/- 0.21 mumol.min-1.mg-1 for cellobiose; K = 0.19 +/- 0.02 mM and V = 29.67 +/- 3.25 mumol.min-1.mg-1 for p-nitrophenyl beta-D-glucopyranoside. Studies of inhibition by products and by alternative product supported an Ordered Uni Bi mechanism for the reaction catalyzed by beta-glucosidase on p-nitrophenyl beta-D glucopyranoside as substrate. Alternative substrates as salicin and cellobiose, a substrate analog such as maltose and a product analog such as fructose were competitive inhibitors in the p-nitrophenyl beta-D-glucopyranoside hydrolysis. PMID- 2107876 TI - Chemical modification of erythropoietin: an increase in in vitro activity by guanidination. AB - Human recombinant erythropoietin (rHuEPO) was chemically modified with several group-specific reagents in order to study the role of each kind of amino-acid residue in its biological activity. Guanidination of the amino groups of the lysine residues yielded derivatives that showed higher activities in vitro than native rHuEPO, whereas amidination had no effect on the activity. By contrast, modification of the positive charges of the lysine residues to neutral or negative charges, such as in carbamylation, trinitrophenylation, acetylation or succinylation, caused a significant loss of rHuEPO activity. Chemical modification of other amino-acid residues, such as arginine and tyrosine residues or carboxyl groups, also led to loss of activity. PMID- 2107877 TI - Urinary neutral glycosphingolipid analysis of patients with Fabry's disease; rapid isocratic elution from high-performance liquid chromatography as per-o benzoyl derivatives. AB - Neutral glycosphingolipids from urinary sediments of six patients with Fabry's disease and 11 members of the family of one propositus were analyzed using high performance liquid chromatography. Per-o-benzoyl derivatives of GlcCer, LacCer, GbOse3Cer and GbOse4Cer were clearly resolved by a solvent mixture of hexane/dioxane/isopropanol (75:25:1, v/v) on a normal-phase silica column. Using our isocratic solvent system, the analysis was completed within 15 min. The smallest amount of glycolipid that could be detected by HPLC was 50 pmol and a linear response was shown at 230 nm up to 400 pmol. The calculated peak area of GbOse4Cer was higher than those of GlcCer, LacCer and GbOse3Cer. The molar ratios of GbOse3Cer to monohexosyl ceramide (CMH) in the urinary sediments were: Fabry hemizygotes, 36.33 +/- 25.54 (n = 6); heterozygotes, 0.94 +/- 0.50 (n = 4); and controls, 0.11 +/- 0.06 (n = 5). The molar ratio CDH/CMH was also higher in patients (8.42 +/- 6.23) than in controls (0.77 +/- 0.23). The female H was a rare example of a carrier with typical clinical manifestations. From the urinary sediment analysis, females E, G and J were suspected to be Fabry heterozygotes, although no clinical signs were observed at the time of examination. PMID- 2107878 TI - Isolation and characterization of human apolipoprotein A-I Fukuoka (110 Glu--- Lys). A novel apolipoprotein variant. AB - A novel genetic variant of apolipoprotein(apo) A-I Fukuoka, has been identified in a Japanese family. This variant has a relative charge of +2 compared to normal apolipoprotein A-I (A-I4), on the isoelectric focusing gels and the same molecular mass and immunologic characteristics as normal apolipoprotein A-I. This variant, transmitted as an autosomal co-dominant inheritance was purified by preparative Immobiline isoelectric focusing. Sequence analysis after cleavage with lysyl endopeptidase and CNBr, followed by high-performance liquid chromatography revealed a single substitution of lysine at position 110, instead of the usual glutamic acid. This mutant apolipoprotein A-I has much the same potential as to activate lecithin-cholesterol acyltransferase. PMID- 2107879 TI - R,R,R-alpha-tocopherol potentiates prostacyclin release in human endothelial cells. Evidence for structural specificity of the tocopherol molecule. AB - Human umbilical vein endothelial cells (HUVEC) in culture synthesize prostacyclin (PGI2) as the predominant metabolite of arachidonic acid which is derived from the deacylation of phospholipids. Under basal-unstimulated condition, PGI2 release from HUVEC is extremely low; however, when endothelial monolayers were preincubated with the natural vitamin E (R,R,R-alpha-tocopherol), we found a dose dependent potentiation of basal PGI2 release. When HUVEC were stimulated with arachidonate or ionophore A23187, there was a dose-dependent increase of PGI2 release in response to tocopherol enrichment. When HUVEC were labelled with [Me 3H]choline followed by A23187 stimulation, a significantly higher lysophosphatidylcholine was found in the tocopherol-enriched cells, suggesting a change in enzymes involved in phosphatidylcholine metabolism. Analysis of these enzymes revealed that phospholipase A2 activity was enhanced by tocopherol enrichment, whereas lysophospholipase and acyl-CoA acyltransferase were unaffected. To determine the specificity of the tocopherol molecule, different analogues were tested for their PGI2 potentiating activity. Results showed that the free hydroxyl group on the chromanol ring as well as the phytyl side-chain are absolutely required to stimulate PGI2 release, whereas, different methyl locations and substituents on the chromanol ring had no effect. These studies demonstrated that tocopherol potentiates basal PGI2 release in HUVEC and in contrast to its reported inhibitory role in rat platelets, myocardium and neutrophils, tocopherol stimulates phospholipase activity in HUVEC. PMID- 2107880 TI - Behavior of acyl carrier proteins on western blots. AB - Acyl carrier proteins (ACPs) from Escherichia coli and Euglena were analyzed on Western blots using rabbit antibodies raised against E. coli ACP. Euglena ACP, unlike that from E. coli, behaves upon electrophoresis under denaturing conditions as its size would predict. Oligomeric forms of both ACPs were evident on Western blots, but the bacterial ACP had more tendency to aggregate. That the oligomeric forms were not due to impurities was shown by their regeneration from low-Mr protein, reaction with antibodies isolated from low-Mr protein, and by molecular weight determination of the ACP by low-angle laser light scattering. PMID- 2107881 TI - Vasopressin and norepinephrine stimulation of inositol phosphate accumulation in rat hepatocytes are modified differently by protein f1nase C and protein kinase A. AB - Rat hepatocytes were maintained in primary monolayer culture for 24 h in the presence of serum. Treatment of hepatocytes with 1 microM 4 beta-phorbol 12 beta myristate 13 alpha-acetate (PMA) for 5-15 min increased membrane-associated protein kinase C activity and concomitantly decreased soluble activity. Membrane protein kinase C activity returned to basal values within 1 h then decreased by more than 50% within 2 h. Prolonged (2-18 h) incubation with PMA did not further decrease protein kinase C activity. Pretreatment of hepatocytes with PMA for 5-15 min had little effect on the subsequent actions of 100 nM vasopressin but abolished the stimulation of inositol phosphate accumulation by 3 nM vasopressin and 20 microM norepinephrine. Long-term exposure (2-18 h) of hepatocytes to 1 microM PMA actually enhanced the effects of vasopressin and 20 microM norepinephrine. The stimulation by norepinephrine (20 microM) of inositol phosphate accumulation was abolished by the alpha 1-adrenergic antagonist prazosin (1 microM), whereas the beta-adrenergic antagonist propranolol (30 microM) had little effect. Addition of 8Br-cAMP (100 microM) or glucagon (10 nM) for 5 min or 8 h had no significant effect alone, but enhanced the subsequent vasopressin stimulation of inositol phosphate accumulation. There was no effect of 8Br-cAMP or glucagon on norepinephrine stimulation of phosphoinositide breakdown. These data indicate that the stimulation of phospholipase C activity in rat hepatocytes by 3 nM vasopressin is enhanced by cyclic AMP-dependent kinase but inhibited by protein kinase C. In contrast, down regulation of protein kinase C markedly enhanced the maximal phosphoinositide response due to both vasopressin and norepinephrine. PMID- 2107882 TI - Serine-proline replacement at residue 127 of NADH-cytochrome b5 reductase causes hereditary methemoglobinemia, generalized type. AB - Hereditary methemoglobinemia is an autosomal recessive disorder characterized by NADH-cytochrome b5 reductase (b5R) deficiency. In an attempt to clarify the molecular mechanisms involved in the enzyme deficiency, we isolated the b5R gene from a patient homozygous for hereditary methemoglobinemia, generalized type, and compared its nucleotide sequence with that of the normal NADH-cytochrome b5R gene. Only one difference was observed; a thymidine at the first position of codon 127 (TCT) was altered to a cytidine in the b5R gene of the patient, resulting in replacement of serine with proline. Dot blot hybridization of the amplified DNA samples with allele-specific oligonucleotide probes showed that the proband and her brothers were homozygous for this mutation and that their father was heterozygous. Although the activity of b5R in lymphoblastoid cells from homozygotes was reduced to 10% of the normal level, RNA blot and protein blot analyses of the lymphoblastoid cells showed that synthesis of b5R messenger RNA and the b5R polypeptide were normal. Serine at residue 127 is presumed to be in an alpha-helix structure that is part of a nucleotide-binding domain. These observations suggest that replacement of Pro-127 causes a significant conformation change in the nucleotide-binding domain that affects electron transport from NADH to cytochrome b5. Functional enzyme deficiency results in a generalized type of hereditary methemoglobinemia. PMID- 2107883 TI - Multimer size dependence of von Willebrand factor binding to crosslinked or noncrosslinked fibrin. AB - von Willebrand factor (vWF) is synthesized in endothelial cells (EC) and may be either secreted constitutively or stored in Weibel-Palade bodies (WPB) for regulated release. Because fibrin stimulates rapid vWF release from EC, we examined the binding of EC synthesized vWF to fibrin. Culture medium containing constitutively secreted vWF was removed from metabolically labeled primary cultures of human umbilical vein EC, and vWF released from WPB was obtained after stimulation by A23187. vWF-deficient fibrinogen with or without factor XIII was added to releasate or media and clotted with thrombin to form crosslinked or noncrosslinked fibrin. vWF was immunopurified from releasate or media before and after clotting, and the amount and multimeric pattern of vWF bound was determined after sodium dodecyl sulfate agarose gel electrophoresis. High molecular weight multimers of vWF, whether secreted constitutively or released from WPB, bound preferentially to fibrin. Multimers of greater than 20 subunits represented 60% +/- 4% (SEM) of A23187 released vWF and 11% +/- 5% of media vWF, but binding to fibrin was similar, 96% +/- 1% and 94% +/- 2%, respectively. A progressively smaller proportion of vWF bound as multimer size decreased, and dimeric vWF binding was least, with 34% +/- 5% binding from A23187 releasate and 51% +/- 4% from media. The amount of vWF binding to crosslinked or noncrosslinked fibrin was similar, and preferential binding of high molecular weight multimers occurred with both. As measured by enzyme-linked immunosorbent assay, 45% +/- 2% of constitutively secreted vWF bound to crosslinked fibrin and 50% +/- 2% to noncrosslinked fibrin. The propolypeptide of vWF did not bind to fibrin. These findings indicate that binding of EC secreted vWF binding to fibrin depends on multimeric size but not on factor XIII crosslinking. This suggests that vWF released from EC in the presence of fibrin will bind locally, thereby facilitating platelet adhesion to the hemostatic plug or thrombus. PMID- 2107884 TI - Characterization and fibrinolytic properties of human omental tissue mesothelial cells. Comparison with endothelial cells. AB - It has been reported that omental fat tissue is a good source of human microvascular endothelial cells. By characterization we demonstrate that the epitheloid cells isolated from omental tissue are not endothelial cells, but mesothelial cells. They contain abundant cytokeratins 8 and 18, which are absent in endothelial cells, and vimentin. No staining with the endothelial-specific antibodies EN-4 and PAL-E is observed. A faint and diffuse staining of von Willebrand factor (vWF) is seen in mesothelial cells, whereas microvascular endothelial cells from subcutaneous fat display vWF in distinct granular structures. Human peritoneal mesothelium produces plasminogen activator-dependent fibrinolytic activity, which is essential in the resolution of fibrous exudates and may therefore be important in preventing the formation of fibrous peritoneal adhesions. This fibrinolytic activity is plasminogen activator-dependent, but has not been fully characterized. We report here that human omental tissue mesothelial cells in vitro produce large amounts of tissue-type plasminogen activator (t-PA), together with type 1 and 2 plasminogen activator inhibitor (PAI 1 and PAI-2). PAI-1 is predominantly secreted into the culture medium, whereas the major part of PAI-2 is found in the cells. No urokinase-type plasminogen activator is detected. On stimulation with the inflammatory mediator tumor necrosis factor (TNF), at least a threefold decrease in t-PA antigen is observed, together with an increase in both PAI-1 and PAI-2. TNF also induces a marked change in cell shape. Whereas TNF and bacterial lipopolysaccharide (LPS) have similar effects on the production of PA inhibitor by human endothelial cells, LPS has no or only a relatively small effect on the fibrinolytic properties of mesothelial cells. The decreased fibrinolytic activity induced by the cytokine TNF may impair the natural dissolution of fibrin deposits at the peritoneum in the presence of an inflammatory reaction. PMID- 2107885 TI - Characterization of a new T-lineage glycoprotein expressed in mature T-cell leukemias and lymphomas. AB - We identified a new human, T-lineage restricted glycoprotein of molecular weight 120 Kd that is expressed primarily in mature T-cell malignancies. The antigen, named TCA-1 (T-cell cytoplasmic antigen), is an intracellular glycoprotein found mainly in the Golgi stacks, although a few cell lines also display surface membrane TCA-1. Many but not all T-cell neoplasms express this antigen. The antigen is absent from neoplastic and normal human tissue outside the T lymphocyte lineage. TCA-1 was identified by murine monoclonal antibodies produced after immunization of mice with T-cell chronic lymphocytic leukemia cells. The glycoprotein is a monomer containing approximately 4% N-linked carbohydrate with terminal D-galactose residues. Partial amino acid sequence analysis of TCA-1 shows homology with an immunoglobulin heavy chain region, which suggests that TCA 1 may belong to the immunoglobulin supergene family of receptor and adhesion molecules. PMID- 2107886 TI - Partial purification and properties of nicotinamide adenine dinucleotide synthetase from human erythrocytes: evidence that enzyme activity is a sensitive indicator of lead exposure. AB - We have examined properties of nicotinamide adenine dinucleotide (NAD) synthetase from human erythrocytes. The enzyme was found to be cold labile and extremely unstable in crude hemolysate, with complete loss of activity occurring after 24 hours at 4 degrees C. However, maintenance of crude hemolysate at 20 to 25 degrees C in the presence of EDTA and KCl increased NAD synthetase stability substantially (half-life = 10 days). Using these conditions, NAD synthetase was purified 3,100-fold with a 29% yield using DEAE-cellulose column chromatography, ammonium sulfate fractionation, and dialysis. The apparent Michaelis-Menten constants for nicotinic acid adenine dinucleotide (NAAD), adenosine triphosphate, Mg2+, glutamine, and K+ were 0.108, 0.154, 1.36, 2.17, and 8.32 mmol/L, respectively. The pH optimum ranged between 6.8 and 7.4, and the molecular weight was estimated to be 483 +/- 5 Kd. The enzyme was markedly inhibited by Pb2+ and Zn2+, with concentrations necessary for 50% inhibition of activity of 1.3 and 2.0 mumol/L, respectively. The incubation of intact red blood cells with lead followed by rigorous washing to remove lead abolished nearly all NAD synthetase activity. In contrast, glucose-6-phosphate dehydrogenase activity, which is not sensitive to lead, was unaffected, whereas pyrimidine 5'-nucleotidase activity, which is sensitive to lead, was decreased 30% to 50% under these conditions. More importantly, patients with lead overburden (34 to 72 micrograms Pb2+/dL blood) all had markedly decreased NAD synthetase activity. These data together with other results suggest that erythrocyte NAD synthetase activity is a sensitive indicator of lead exposure in humans. PMID- 2107887 TI - Intranasal desmopressin (DDAVP) by spray in mild hemophilia A and von Willebrand's disease type I. AB - Desmopressin acetate (1-desamino-8-D-arginine vasopressin, DDAVP) has mostly been given by the parenteral route for the treatment of mild hemophilia A and von Willebrand's disease type I. In the present study the hemostatic effects of desmopressin acetate administered intranasally by spray in a dose of 300 micrograms and intravenously 0.3-0.4 micrograms/kg were assessed and compared in 8 patients with hemophilia A and 22 patients with von Willebrand's disease type I. A bioequivalent response to intravenous and intranasal desmopressin acetate was found in Factor VIII coagulant activity (VIII:C) in the hemophilia patients. In the von Willebrand patients, an equivalent shortening of the bleeding time was seen after the two modes of administration, even though intravenous injection gave a higher increase in plasma levels of VIII:C and vWF:Ag. In five patients with von Willebrand's disease the duration of the spray effect on VIII:C and vWF:Ag was followed for 24 h. After 12 h the mean level of VIII:C was 1.4, and of vWF:Ag 1.5, times the basal level. The findings suggest that the spray can be recommended for home or prophylactic treatment of patients with mild hemophilia A and von Willebrand's disease. PMID- 2107888 TI - Leukaemia and nuclear installations. PMID- 2107889 TI - Bovine spongiform encephalopathy. PMID- 2107890 TI - The new dermatology. PMID- 2107891 TI - AIDS in Thailand. PMID- 2107892 TI - Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. AB - OBJECTIVE: To examine whether the observed excess of childhood leukaemia and lymphoma near the Sellafield nuclear plant is associated with established risk factors or with factors related to the plant. DESIGN: A case-control study. SETTING: West Cumbria health district. SUBJECTS: 52 Cases of leukaemia, 22 of non Hodgkin's lymphoma, and 23 of Hodgkin's disease occurring in people born in the area and diagnosed there in 1950-85 under the age of 25 and 1001 controls matched for sex and date of birth taken from the same birth registers as the cases. MAIN OUTCOME MEASURES: Antenatal abdominal x ray examinations, viral infections, habit factors, proximity to and employment characteristics of parents at Sellafield. RESULTS: Expected associations with prenatal exposure to x rays were found, but little information was available on viral illnesses. Relative risks for leukaemia and non-Hodgkin's lymphoma were higher in children born near Sellafield and in children of fathers employed at the plant, particularly those with high radiation dose recordings before their child's conception. For example, the relative risks compared with area controls were 0.17 (95% confidence interval 0.05 to 0.53) for being born further than 5 km from Sellafield 2.44 (1.04 to 5.71) for children of fathers employed at Sellafield at their conception, and 6.42 (1.57 to 26.3) for children of fathers receiving a total preconceptual ionising radiation dose of 100 mSv or more. Other factors, including exposure to x rays, maternal age, employment elsewhere, eating seafood, and playing on the beach did not explain these relationships. Focusing on Seascale, where the excess incidence has predominantly been reported, showed for the four out of five cases of leukaemia and one case of non-Hodgkin's lymphoma whose fathers were employed at Sellafield and for whom dose information was obtained that the fathers of each case had higher radiation doses before their child's conception than all their matched control fathers; the father of the other Seascale case (non-Hodgkin's lymphoma) was not employed at the plant. These results seem to explain statistically the geographical association. For Hodgkin's disease neither geographical nor employment associations with Sellafield were found. CONCLUSIONS: The raised incidence of leukaemia, particularly, and non-Hodgkin's lymphoma among children near Sellafield was associated with paternal employment and recorded external dose of whole body penetrating radiation during work at the plant before conception. The association can explain statistically the observed geographical excess. This result suggests an effect of ionising radiation on fathers that may be leukaemogenic in their offspring, though other, less likely, explanations are possible. There are important potential implications for radiobiology and for protection of radiation workers and their children. PMID- 2107893 TI - Methods and basic data of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. AB - OBJECTIVE: To examine whether the observed excess of childhood leukaemia and lymphoma near the Sellafield nuclear plant is associated with established risk factors or with factors related to the plant. DESIGN: A case-control study. SETTING: West Cumbria health district. SUBJECTS: 52 Cases of leukaemia, 22 of non Hodgkin's lymphoma, and 23 of Hodgkin's disease occurring in people born in the area and diagnosed there in 1950-85 under the age of 25 and 1001 controls matched for sex and date of birth taken from the same birth registers as the cases. MAIN OUTCOME MEASURES: Antenatal abdominal x ray examinations, viral infections, habit factors, proximity to and employment characteristics of parents at Sellafield. RESULTS: Ascertainment of cases through multiple sources was as complete as possible, and the diagnosis was established for nearly all cases from hospital records and by independent pathological review when suitable material (60% (58) of cases) was available. Identification and tracing of the parents of cases and controls enabled questionnaires to be forwarded to 730 (66%), and 467 (64%) of the questionnaires were returned completed. Obstetric records were located for 481 (44%) of the relevant births, more frequently in recent years. Linkage of study subjects to the Sellafield workforce file enabled dates of employment and records on external doses of whole body ionising radiation to be obtained. Concordance of information from duplicate sources (when available) was reasonably high with no indications of bias. CONCLUSION: Overall the collected data were sufficiently reliable for detailed analysis and careful interpretation. PMID- 2107894 TI - Attitudes to viability of preterm infants and their effect on figures for perinatal mortality. AB - OBJECTIVE: To examine how local attitudes to management of extreme preterm labour can influence data on perinatal mortality. DESIGN: One year prospective study in a geographically defined population. SETTING: The 17 perinatal units of Trent region. PATIENTS: All preterm infants of less than or equal to 32 weeks' gestation in the Trent region. INTERVENTIONS: Infants who had been considered viable at birth were referred for intensive care; those who had been considered non-viable received terminal care. MAIN OUTCOME MEASURES: Whether each infant was born alive, dead, or alive but considered non-viable. RESULTS: Large differences were observed among units in the rates of delivery of infants of less than or equal to 27 weeks' gestation (rates varied from 7.2 to 0 per 1000 births). These differences were not present in the data relating to infants of between 28 and 32 weeks' gestation. The variation seemed to result from different approaches to the management of extreme preterm labour--that is, whether management took place in a labour ward or a gynaecology ward. CONCLUSIONS: Place of delivery of premature babies (less than or equal to 27 weeks' gestation) may influence classification and hence figures for perinatal mortality. In addition, the fact that the onus of judgment regarding viability and classification is often placed on relatively junior staff might also affect the figures for perinatal mortality. The introduction of a standard recording system for all infants greater than 500 g would be advantageous. PMID- 2107895 TI - Prolonged endometrial stimulation associated with oestradiol implants. AB - OBJECTIVE: To provide information on endometrial stimulation after discontinuation of treatment with oestradiol implants. DESIGN: Long term follow up of withdrawal bleeding patterns in women taking progestogens cyclically every month after oestradiol implant treatment was ended. SETTING: Specialist menopause clinic. SUBJECTS: 10 Postmenopausal patients (at least 12 months' amenorrhoea after the last spontaneous period) who were treated with oestradiol implants for typical symptoms of oestrogen deficiency. The oestradiol dose was 50 mg, reimplantation occurring roughly every six months. Patients subsequently either needed to discontinue the hormone treatment for medical reasons or expressed a desire to stop treatment. MAIN OUTCOME MEASURE: Duration of endometrial stimulation--defined as the presence of withdrawal bleeding in response to progestogen given cyclically--after insertion of the last oestradiol implant. RESULTS: Four patients eventually stopped bleeding, their mean duration of bleeding being 35 months (range 27-43 months). One patient required hysterectomy 26 months after the last implantation because of persistent irregular bleeding despite treatment with high doses of progestogen. Three patients bled for 22, 30, and 36 months and then restarted oestrogen treatment because symptoms returned. The last two patients subsequently continued to bleed 12 and 21 months after the last implantation. CONCLUSIONS: The duration of endometrial stimulation after implantation can be prolonged, up to 43 months. Insertion of oestradiol implants can carry a long term commitment to the cyclical administration of progestogen and regular withdrawal bleeding if endometrial hyperplasia and carcinoma are to be avoided. PMID- 2107896 TI - Omeprazole for duodenal ulceration in Crohn's disease. PMID- 2107897 TI - Detection of pseudodiarrhoea by simple clinical assessment of intestinal transit rate. PMID- 2107898 TI - Anxiety caused by abnormal result of cervical smear test: a controlled trial. PMID- 2107900 TI - Counselling needs and experience of junior hospital doctors. AB - A sample of 106 senior house officers who had graduated from Nottingham University in 1987 was surveyed about their experience of and need for careers guidance, performance appraisal, and stress counselling. Of the 80 who replied, a quarter had received no careers guidance and a quarter no feedback about their work performance. Many reported having had difficulties in their post, but few had received help from senior staff or their consultant. The perceived needs for counselling were considerable. Careers counselling was thought to be essential in the preregistration year by all of the doctors and in senior house officer posts by three quarters. Nearly all would have chosen regular appraisal and nearly half wanted counselling for particular difficulties. Doctors in the training grades clearly believed that they needed counselling, but in most cases they did not receive it. PMID- 2107899 TI - Antibiotic prescribing: the need for a policy in general practice. AB - OBJECTIVE: To see whether changes in prescribing of oral antibacterials in Northern Ireland show the need for a community antibiotics policy. DESIGN: Analysis of prescribing totals for several oral antibiotics obtained retrospectively from the prescription pricing bureau for the years 1983-7. SETTING: Audit of anti-infective prescribing in general practice in Northern Ireland over five years. MAIN OUTCOME MEASURE: Respective usage of agents defined as "common" and "occasional" in 1983. RESULTS: There was a gradual decrease in the relative use of common agents from 82% of the total in 1983 to 77% in 1987 together with a complementary increase in the use of occasional agents from 5% to 10%. Pronounced changes were noted in the use of amoxycillin, ampicillin, erythromycin, minocycline, doxycycline, and amoxycillin-clavulanic acid. CONCLUSION: Though this survey found reasonably conservative prescribing, the trend towards increased use of occasional agents has both clinical and cost implications which could be addressed by the use of a prescribing formulary. PMID- 2107902 TI - ABC of transfusion. Infectious complications of blood transfusion: viruses. PMID- 2107901 TI - HIV testing in patients with end stage renal disease. AB - One hundred and twenty eight British and Irish nephrologists were questioned about their policy for HIV testing of patients with end stage renal failure being considered for renal replacement therapy. A total of 101 (79%) replied. In the case of candidates for dialysis roughly one third of respondents tested only people they considered at risk of infection with HIV and nearly one fifth considered testing unnecessary. In the case of candidates for transplantation routine HIV testing was carried out by 68 of 100 nephrologists; 22 tested only patients "at risk" and 10 did not test. A positive HIV test result was considered by most but not all respondents (63/86) to exclude patients from transplantation. Twenty four of 88 nephrologists considered that HIV positivity should exclude patients from haemodialysis, but only seven of 87 would exclude such patients from peritoneal dialysis. Similar attitudes pertained for patients with end stage renal failure who refused HIV testing. Testing with the patient's knowledge and consent was the policy of two thirds of nephrologists, but a patient's signature was obtained by only 24 of 88. There should be a consensus on practice for HIV testing of patients with end stage renal failure. PMID- 2107903 TI - How to pay your way through medical school. PMID- 2107904 TI - Genital warts: need to screen for coinfection. PMID- 2107905 TI - Medical audit. PMID- 2107906 TI - Stone fish bite. PMID- 2107907 TI - Ovarian failure after total body irradiation. PMID- 2107908 TI - Single dose prophylaxis in colonic surgery. PMID- 2107909 TI - Organs for transplantation. PMID- 2107910 TI - Why are the Japanese living longer? PMID- 2107911 TI - Shortage of therapists. PMID- 2107912 TI - Hazards of blood splashes. PMID- 2107913 TI - Overprescription of cholera vaccine. PMID- 2107914 TI - Electromagnetic radiation in homes. PMID- 2107915 TI - Hospital formularies. PMID- 2107916 TI - Death after flumazenil. PMID- 2107917 TI - Hearing problems of elderly people. PMID- 2107918 TI - Selective decontamination of the digestive tract. PMID- 2107919 TI - Fibromuscular dysplasia of renal arteries and acute loin pain. PMID- 2107920 TI - Effective use of regional intensive therapy units. PMID- 2107921 TI - Blood transfusion services and the European community. PMID- 2107922 TI - Dangers of thrombolysis. PMID- 2107923 TI - Bulimia nervosa. PMID- 2107924 TI - Community care. PMID- 2107925 TI - Clinical directorates. PMID- 2107926 TI - Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. Groupe Francais d'Etude de la Tetrahydroaminoacridine. AB - OBJECTIVE: To see whether combined treatment with oral tacrine (tetrahydroaminoacridine; THA) and lecithin improves the symptoms of patients with Alzheimer's disease. DESIGN: Multicentre double blind, placebo controlled, random order crossover trial with individual determination of maximum tolerated dosage and four month follow up. SETTING: Outpatient departments at six university neurological centres. PATIENTS: 67 Outpatients (24 men, 43 women) aged 53-81 (mean 66 (SD 7.3)) selected according to the following criteria: probable Alzheimer's disease as defined by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; absence of mood disorder; mini mental state score lower than 26; availability of a close relative able to complete questionnaires; and informed consent of the patient or his or her closest relative, or both. INTERVENTIONS: Mean of 114 mg tacrine or placebo daily plus 1200 mg lecithin daily given in three divided doses for one four week active treatment period and one four week control period without washout at crossover. MAIN OUTCOME MEASURES: Cognitive state as assessed by Folstein's mini mental state rating scale, behavioural state as assessed by the Stockton geriatric rating scale, and overall state as assessed with a visual analogue scale rated by both the relative and the physician. RESULTS: Compared with placebo tacrine did not improve either the mini mental state score (mean 14.9 (SD 7.3) v 14.8 (7.3)) or the Stockton geriatric score (28.2 (15.7) v 28.7 (17.8)), but a slight and statistically significant improvement occurred in the physician's score on the visual analogue scale (6.3 (10.2) v 11.6 (17.9)). Seven patients dropped out. Six patients were excluded because of acute hepatitis and one withdrew for personal reasons not related to treatment. Two other patients developed acute hepatitis at the end of the eight week crossover trial and another during the follow up study. Twenty patients complained of gastrointestinal side effects. CONCLUSIONS: Neither short term nor long term treatment with oral tacrine at dosages lower than 125 mg/day improves the symptoms of Alzheimer's disease. Moreover, these dosages may induce hepatitis (nine of 67 patients in this series). PMID- 2107927 TI - Risk of malaria in British residents returning from malarious areas. AB - OBJECTIVES: To identify which British residents travelling abroad are at greatest risk of malaria infection, and to determine the efficacy of malaria chemoprophylaxis for preventing P falciparum infections in tropical Africa. DESIGN: Prospective cohort study (case-base linkage) with routine national surveillance systems. Denominators (base population) were obtained from monitoring a random sample of returning British travellers with the international passenger survey. Numerators (cases) were obtained from reports of malaria infections in British residents, through the Malaria Reference Laboratory network. SETTING: International passenger survey conducted at passport control of international airports in Britain. Malaria reports received nationally were collated centrally in London. SUBJECTS: 2948 British residents (0.2%) returning to Britain in 1987 randomly selected and questioned and 1052 British residents with microscopically confirmed malaria infections in 1987, whose case reports were reviewed and on whom additional data were collected by postal survey. MAIN OUTCOME MEASURES: Annual incidence subdivided by categories of risk. Chemoprophylactic efficacy for east and west Africa by principal regimens and compliance. RESULTS: Annual rates of reported infection per 100,000 travellers to Oceania were 4100; to west and east Africa were 375 and 172 respectively; to Latin America, the Far East, and the Middle East were 12, 2, and 1 respectively. Immigrants visiting friends and relatives in Ghana and Nigeria were at greatest risk (1303 and 952 per 100,000 respectively) in west Africa. Business travellers to Kenya experienced the highest attack rates in east Africa (465 per 100,000). Age-sex specific attack rates varied by region. No prophylaxis was reported to have been used by 23% of British visitors to west Africa, 17% to east Africa, 46% to central or southern Africa, and 58% visiting south Asia. The efficacy of chloroquine plus proguanil against P falciparum infection was 73% and 54% in west and east Africa respectively. Lower values were obtained for chloroquine alone and proguanil alone. The efficacy of Maloprim (pyrimethamine-dapsone) was 61% in west Africa, but only 9% in east Africa. Visitors to west Africa who did not comply with their chemoprophylactic regimen were at a 2.5-fold higher risk of infection than fully compliant users. Non-compliant visitors to east Africa had similar rates of infection as non-drug users. CONCLUSIONS: In 1987 chloroquine plus proguanil was the preferred chemoprophylactic regimen for P falciparum infection in Africa; antimalarial drugs must be taken regularly to be effective. PMID- 2107928 TI - Trauma services requirements in a district general hospital serving a rural area. AB - OBJECTIVE: To assess the demands made on a regional trauma centre by a district trauma unit. DESIGN: Two part study. (1) Prospective analysis of one month's workload. (2) Retrospective analysis of one year's workload by using a computer based records system. Comparison of two sets of results. SETTING: Accident unit in Gwynedd Hospital, Bangor. PATIENTS: (1) All patients who attended the accident unit in August 1988. (2) All patients who attended the accident unit in the calendar year April 1988-April 1989. MAIN OUTCOME MEASURE: Workload of a district trauma unit. RESULTS: In August 1988 there were 2325 attendances; 2302 of these were analysed. In all, 1904 attendances were for trauma; 213 patients were admitted to the trauma ward and 103 required an operation that entailed incision. Patients who attended the unit had a mean (range) injury severity score of 2-13 (0-25). Only two patients had injuries that a district general hospital would not be expected to cope with (injury severity score greater than 20). In the year April 1988-April 1989, 21,007 patients attended the unit. In all, 17,958 attendances were for orthopaedic injuries or injuries caused by an accident; 1966 patients were admitted to the unit. CONCLUSIONS: Most trauma is musculoskeletal and relatively minor according to the injury severity score. All but a few injuries can be managed in district general hospitals. In their recent report the Royal College of Surgeons has overestimated the requirements that a British district general hospital would have of a regional trauma centre. PMID- 2107929 TI - Hearing disability in people aged 50-65: effectiveness and acceptability of rehabilitative intervention. AB - OBJECTIVE: To determine the best means of detecting hearing disability in subjects aged 50-65 and whether rehabilitative intervention is acceptable in this age group. DESIGN: Questionnaire survey of patients on general practice age-sex registers. Two types of questionnaire were used, one being based on the closed set approach of the Institute of Hearing Research questionnaire, which had been used in a pilot study, and the other being a simplified version of this questionnaire developed by the Welsh Hearing Institute and based on open set questions. Questionnaires were sent up to three times, and any patients who had not responded two months after the last posting were personally contacted. SETTING: Two general practices in Glyncorrwg and Blaengwynfi in the Afan valley, West Glamorgan. PATIENTS: 271 Patients in Glyncorrwg (136 men, 135 women) and 333 patients in Blaengwynfi (173 men, 160 women) aged 50-65. INTERVENTIONS: All patients indicating hearing disability in answering the questionnaires were invited to attend for a evaluative session in their village. After audiometric testing advice and arrangements for fitting a hearing aid were offered as appropriate. MAIN OUTCOME MEASURES: Response rates and prevalence of hearing disability before intervention and of possession of hearing aids before and after intervention. RESULTS: After three postings and personal contact the response rate was 98% (266/271) in Glyncorrwg, where the complex questionnaire was used, and 97% (322/333) in Blaengwynfi. The prevalence of hearing disability was respectively 53% (141/266) and 46% (148/322) and the prevalence of owning a hearing aid 7% (19/266) and 8% (24/322). After intervention the possession of hearing aids rose to 24% (64/266) in Glyncorrwg and 22% (71/322) in Blaengwynfi; six months later the aids were being used regularly. A direct comparison of the two questionnaires in 69 subjects from Blaengwynfi showed no significant differences in the amount of disability detected by each one. The first posting of questionnaires detected 65% (189/289) of the hearing disability in the two villages or 78% (72/92) of those prepared to accept hearing aids for the first time; 96% (88/92) of those who accepted hearing aids were detected by two postings. CONCLUSIONS: Simple questionnaires are effective in detecting hearing disabilities in people aged 50-65, and intervention was acceptable in many of those who reported having difficulties in hearing. The response rates from successive postings suggest that two postings are sufficient in terms of the return in detecting those who will accept intervention. PMID- 2107930 TI - Association between living conditions in childhood and myocardial infarction. PMID- 2107931 TI - Intravenous thrombolysis for suspected myocardial infarction: a cautionary note. PMID- 2107932 TI - Telematics: a new tool for epidemiological surveillance of diarrhoeal diseases in the Aquitaine sentinel network. AB - A sentinel health information system using telematics and a network of general practitioners was set up in Aquitaine in south western France in 1986. Among the health problems under surveillance was acute diarrhoea. Data for each patient who fulfilled the usual case definition for acute diarrhoea were reported by general practitioners using home terminals (Minitels) connected to a central computer by telephone. Over one year 2234 cases of diarrhoea were reported, the incidence varying from 0.8 to 1.5 cases per doctor per week. Seasonal variations in incidence were observed, with peaks in the winter and in the summer. Only 379 (17%) episodes of diarrhoea were classified as severe, and these patients consulted their general practitioners earlier than patients whose diarrhoea was less severe. Foreign travel was rarely found in the patients' histories, but clusters of cases were found in communities (4.6%) and in families (22.3%). The advantages of this system were easy reporting and immediate feedback, but it was difficult to extrapolate the data, and the system was inadequate for intervening in outbreaks of diarrhoeal disease. Our knowledge of diarrhoeal diseases in south west France improved. PMID- 2107934 TI - ABC of Transfusion. Platelet and granulocyte transfusions. PMID- 2107933 TI - Streptokinase in acute aortic dissection. PMID- 2107935 TI - Drugs in cerebral and peripheral arterial disease. PMID- 2107936 TI - Death of children with head injury. PMID- 2107937 TI - Cognitive impairment and death in the elderly. PMID- 2107938 TI - Audit in practice. PMID- 2107939 TI - Child health surveillance. PMID- 2107940 TI - The dystonias. PMID- 2107941 TI - Self injection treatment for impotence. PMID- 2107942 TI - Treatment of subdural haematoma. PMID- 2107943 TI - Benefits of animal research and the doctor's responsibility. PMID- 2107944 TI - Measuring blood pressure in the elderly. PMID- 2107945 TI - University hospitals and the NHS review. PMID- 2107946 TI - Construction of clinical scoring systems. PMID- 2107947 TI - Emergency services in Rhodes. PMID- 2107948 TI - Acute parkinsonism associated with flurbibrofen. PMID- 2107949 TI - Gynaecomastia induced by angiotensin converting enzyme inhibitor. PMID- 2107950 TI - Severe magnesium toxicity after magnesium sulphate enema in a chronically constipated child. PMID- 2107951 TI - Viruses: variation and its significance in the biological world. PMID- 2107952 TI - Calbindin D28k is essentially located in the colonic part of the toad intestine. AB - The distribution of calbindin D28k in the digestive system and the urinary bladder of the toad was investigated using immunohistochemistry and Western blotting. By analogy with mammals and birds, the protein was expected to be located preferentially in the duodenal part of the intestine. Interestingly, absorptive cells of the duodenum were totally devoid of calbindin D28k while the colon contained high amounts of the calcium-binding protein. This reversed polarity of calbindin D28k content in the toad intestine should obviously correspond to a different scheme of calcium absorption regulation between amphibians and higher vertebrates. Calbindin D28k containing neuroendocrine-like cells were found scattered in the proximal parts of the gut with a similar distribution to what has been described in rat and chick intestine. The oesophagus, the stomach, and the intrinsic nervous system of the intestine were negative. No significant amounts of the proteins were found in the urinary bladder, which is known to be a site of Ca2+ active transport. PMID- 2107953 TI - Petit mal status: an unusual cause of confusion. PMID- 2107954 TI - Fluvoxamine and lithium: an unusual interaction. PMID- 2107955 TI - Fluvoxamine and liver enzymes. PMID- 2107956 TI - Synthesis of prostaglandins I2 and E2 by the canine gallbladder in vitro: studies using a new incubation chamber. AB - Using a specially designed incubation chamber, differential synthesis and the response to added arachidonic acid (25 mM) and L-alpha-phosphatidylcholine (LAP; 2 mM) was quantified in gallbladders from male and female dogs. Prostaglandin I2 (PGI2) was the predominant prostanoid synthesized, and tissues from females produced much more PGI2 under basal conditions than did gallbladders harvested from male dogs. Addition of arachidonic acid stimulated PGI2 synthesis by almost 100 per cent. Arachidonate-stimulated mucosal and serosal production of PGI2 were (mean(s.e.m.] comparable, 343(178) and 375(89) pg/cm2/min, respectively. Gallbladders from female animals synthesized significantly more PGI2 than did tissue from males. Indomethacin inhibited PGI2 synthesis in a dose-response manner; at 7 x 10(-5) M, prostanoid synthesis was inhibited by greater than 80 per cent. Arachidonic acid did not stimulate prostaglandin E2 (PGE2) production by gallbladder tissue. LAP similarly stimulated PGI2 biosynthesis, but in contrast to the effect of arachidonic acid, the effect was significantly greater in the serosa than the mucosa, 355(107) and 213(59) pg/cm2/min, respectively. LAP also stimulated PGE2 biosynthesis by the canine gallbladder in a pattern very similar to that of PGI2. Based on the differences in response to the two agents added, we conclude that arachidonic acid and L-alpha-phosphatidylcholine stimulate prostaglandin biosynthesis via independent pathways. We advocate the use of the incubation chamber for the assessment of prostanoid biosynthesis by the gallbladder in vitro. PMID- 2107957 TI - Tissue plasminogen activator in peripheral arterial thrombolysis. AB - Thirty acute peripheral arterial thromboses in 28 patients were treated with local low-dose intra-arterial recombinant tissue plasminogen activator (t-PA). All patients received 0.5 mg h-1 t-PA and 15 also received 250 units h-1 of intra arterial heparin. Overall limb salvage at 30 days was 83 per cent (25 out of 30 limbs). Mean(s.d.) ankle/brachial index was increased by 0.53(0.26) and there was no significant difference between the group receiving t-PA alone and that receiving t-PA and heparin. No strokes or major haemorrhages occurred but there were four (13 per cent) minor haematomas associated with the catheter entry site. There were four (13 per cent) deaths from myocardial infarction occurring between 5 and 21 days after treatment. Rethrombosis occurred in four cases (13 per cent). In two patients following t-PA alone, rethrombosis occurred after 2 and 11 days. Limb salvage was achieved with a successful repeat thrombolysis and a femoropopliteal graft respectively. Rethrombosis after t-PA and heparin occurred after 30 days in two patients due to poor run-off and extensive proximal atheromatous disease respectively. t-PA is a safe, effective thrombolytic agent when given as a low-dose intra-arterial infusion. The addition of low-dose heparin does not produce any significant benefit. PMID- 2107958 TI - Effects of an amino acid solution enriched with either branched chain amino acids or ornithine-alpha-ketoglutarate on the postoperative intracellular amino acid concentration of skeletal muscle. AB - Patients undergoing elective cholecystectomy provide a highly reproducible model of the effects of trauma on intermediary metabolism. Three parenteral nutrition regimens were given to groups of eight such patients. An isonitrogenous total parenteral nutrition, including a commercially available amino acid solution, an amino acid solution enriched with branched chain amino acids or one supplemented with ornithine-alpha-ketoglutarate, was given after operation. The intra cellular free amino acid concentrations of skeletal muscle were determined in tissue specimens obtained before operation and on the third postoperative day using a percutaneous needle biopsy technique. The mean (s.e.m.) decrease in the concentrations of free intracellular glutamine on the third postoperative day was less pronounced (P less than 0.05) in the ornithine-alpha-ketoglutarate group (18.8(7.5)per cent) than in the control group (39.4(5.1)per cent) or the branched chain amino acid group (45.3(6.1)per cent). In conclusion, in the immediate postoperative period total parenteral nutrition supplemented with ornithine-alpha ketoglutarate countered the decline in the muscle free glutamine. No difference in this parameter was seen between the control group and the branched chain amino acid group. PMID- 2107959 TI - [Associative learning in a neuromimetic network with local competitions]. AB - Presented here is a neuromimetic model for the learning of associations between activity patterns originating from recoding layers. These layers are described as networks of cellular clusters made up of competitive formal neurons. A rule of synaptic plasticity with improved neurobiological realism is proposed; it allows for fast learning of large sets of associations. PMID- 2107960 TI - [Timing niches of 3 species of Plasmodium coexisting in a rodent in Central Africa]. AB - Freeze-thawing of blood infected with malaria parasites is a technique which brings about the destruction of all stages except the merozoites and makes possible investigations on the behaviour of these merozoites and the schizogonic rhythm of each species. Merozoites of Plasmodium y. yoelii remain in the blood during the 24 hrs. following inoculation; it is concluded that their penetration in the erythrocytes occurs gradually during this time. Synchronism is poor. Merozoites of P. vinckei petteri penetrate rapidly inside the erythrocytes independently of the time of inoculation. Infection is therefore synchronous and does not follow the circadian rhythm of the host. Penetration of merozoites of P. c. chabaudi is predominant at midnight when rodents are maintained with a normal circadian rhythm (light from 8 am to 8 pm) and predominant at noon when the rhythm of the host is inverted (light from 8 pm to 8 am). Infection is therefore synchronous and follows the host rhythm. The three species of plasmodia coexisting in Thamnomys rutilans from CAR show the same periodicity of 24 hrs. but, because of differences in the biology of the merozoites, they occupy three distinct niches. These notions have great practical implications in chronotherapy, as many data lead to the idea that merozoites are drug resistant. PMID- 2107961 TI - Third International Workshop on Cells and Cytokines in Bone and Cartilage. 8-11 April 1990, Davos, Switzerland. Abstracts. PMID- 2107963 TI - Sarcomas in three generations of a family with neurofibromatosis. AB - The development of sarcomas in three generations of a family with neurofibromatosis (NF) is described. A 7-month-old boy developed a prostatic rhabdomyosarcoma. Family history revealed that his maternal grandmother had died of a malignant peripheral nerve sheath tumor at age 37 years and had been affected with neurofibromatosis. His mother (aged 36 years) has also developed a malignant peripheral nerve sheath tumor and NF has been confirmed in both mother and son. This family illustrates a cluster of sarcomas associated with NF and shows the importance of thorough investigation of reported family illnesses. PMID- 2107962 TI - Effectiveness of Haemophilus influenzae type b vaccines. AB - PURPOSE: To determine the clinical effectiveness of Haemophilus influenzae type b (Hib) vaccines. STUDY IDENTIFICATION AND SELECTION: Computerized searches of MEDLINE, EMBASE and SCISEARCH databases were performed, and the reference list of each retrieved article was reviewed. Two prospective clinical trials of Hib polyribosyl ribitol phosphate conjugated with diphtheria toxoid (PRP-D) were identified. In addition, one cohort study of the PRP-D vaccine, two trials of the PRP vaccine, five case-control studies of the PRP vaccine and 10 randomized controlled trials of the immunogenicity of the PRP-D vaccine were identified. DATA EXTRACTION: Study quality was assessed and descriptive information concerning the study populations, the interventions and the outcome measurements was extracted. RESULTS: The difference in the effectiveness of the PRP-D vaccine between the prospective trials, in which a three-dose schedule had been used beginning at 2 to 3 months of age, was clinically important (37% v. 83%) but not statistically significant. The PRP vaccine, which induces lower antibody responses than the PRP-D vaccine does, was clinically effective only in a subgroup of one prospective trial; 90% effectiveness was reported among children 18 to 60 months of age. CONCLUSIONS: Hib vaccine appears to be less effective in high-risk populations. None the less, because of the large variation in baseline risk, the number of children who would have to be vaccinated to prevent one case of invasive Hib disease is substantially less for high-risk than for low-risk populations. The vaccination of children at high risk, such as native children, with the PRP-D vaccine using a four-dose schedule (at 2, 4, 6 and 14 months of age) seems warranted. The currently available evidence does not strongly support a policy of universal vaccination with either a one-dose or a four-dose schedule. PMID- 2107964 TI - Inhibitors of lipoxygenase have antiproliferative effects on P815 murine mastocytoma cells. AB - The effect of a variety of inhibitors of prostaglandin synthase, lipoxygenase and phospholipase on the growth of P815 murine mastocytoma cells was examined. Only lipoxygenase inhibitors substantially reduced growth, presumably by inhibiting the production of arachidonic acid metabolites rather than causing arachidonate accumulation since excess arachidonic acid did not reverse growth inhibition. Evidence is presented that production of leukotrienes B4, C4, D4 or E4 was not involved. Other metabolites of arachidonic acid were not excluded. A role for lipoxygenase in growth signal transduction in these and other cells is suggested. PMID- 2107965 TI - Effect of dietary butylated hydroxytoluene on the in vivo distribution, metabolism and DNA-binding of 7,12-dimethylbenz[a]anthracene. AB - The effect of dietary intake of butylated hydroxytoluene (BHT) (0.6%) on the in vivo distribution, metabolism and DNA-binding of intragastrically administered 7,12-dimethylbenz[a]anthracene (DMBA) was evaluated. Urinary excretion of DMBA increased, blood content of metabolized DMBA increased and blood content of non metabolized DMBA decreased for rats fed the diet containing BHT as compared to rats fed the control diet. The binding of DMBA to both liver and mammary DNA decreased for rats fed the diet containing BHT as compared to controls. The liver activities of glutathione-S-transferase (GST), epoxide hydrolase (EH) and NAD(P)H quinone reductase (QR) increased in response to BHT feeding. However, no increase in the mammary tissue activities of these enzymes was observed. These results suggest that the ability of dietary BHT to inhibit the initiation of DMBA-induced mammary carcinogenesis partly may be due to decreased binding of DMBA to mammary DNA. This effect of BHT is not due to an increase in mammary tissue activities of GST, EH and QR, enzymes involved in carcinogen detoxification, but may involve increased liver metabolism of DMBA to products that do not bind to DNA. PMID- 2107966 TI - Enhanced resistance to an antigenic tumor in immunosuppressed mice by dietary retinyl palmitate plus canthaxanthin. AB - Retinoids and certain carotenoids, e.g., beta-carotene and canthaxanthin, have been found to prevent photocarcinogenesis in mice and also to act as immunoenhancers. The hypothesis that retinoids and carotenoids inhibit photocarcinogenesis by preventing UV induction of immunosuppression predicts that mice treated with these agents before and during periods of UV radiation treatments should be as resistant as unirradiated mice to an antigenic UV-induced tumor. To test this prediction, mice were fed 120 IU of retinyl palmitate per gram of diet, and/or 1% canthaxanthin, before UV irradiation treatments began, and during the entire experiment. After 4.95 x 10(5) Jm-2, delivered over 12 weeks, resistance of mice to antigenic UV-induced tumor implants (UV20) was studied. Dietary supplementation with retinyl palmitate plus canthaxanthin, but not with either agent alone at these doses, prevented the enhanced growth of UV20 in UV irradiated mice. PMID- 2107967 TI - Long term effects of benzo(a)pyrene on the activity of NAD(P)H:quinone reductase in the forestomach and glandular stomach of ICR/Ha mice. AB - The present study is part of an effort to identify biomarkers for various stages of preneoplasia. For this purpose, quinone reductase [NAD(P)H:quinone oxidoreductase, EC 1.6.99.2] (QR) activity in the forestomach of ICR/Ha mice was investigated at successive time points during benzo(a)pyrene (BP)-induced carcinogenesis. Six mg of BP in 0.2 ml of cottonseed oil or cottonseed oil alone were given orally twice a week for 2 weeks to female ICR/Ha mice. Ten mice from each group were sacrificed sequentially at 2-week intervals, and the QR activity was determined in the forestomach, a target tissue for BP carcinogenicity, and also in the glandular stomach, a non-target tissue. QR was significantly increased in the cytosolic, microsomal, and mitochondrial fractions of the forestomach of BP-treated animals. There was no significant increase in this activity in any fraction of the glandular stomach. The increases in QR activity in the subcellular fractions of the forestomach from BP-treated animals showed a two-surge pattern. The first was manifested at 2 weeks. The second, found at week 6, continued throughout the remaining course of the experiment. To our knowledge, the time course of changes in QR activity in the three subcellular fractions of mouse forestomach during BP carcinogenesis has not been demonstrated previously. PMID- 2107968 TI - Phorbol esters mediate phospholipid-free activation of rat brain protein kinase C. AB - The present study provides evidence that rat brain protein kinase C elicits a phosphotransferase activity towards histone and undergoes autophosphorylation in the absence of phosphatidylserine. The tumor promoter 12-O-tetradecanoylphorbol 13-acetate binds to and activates protein kinase C in a phospholipid-free reaction. The apparent activation constant (Ka = 2.7 nM) is not modified by the absence of phospholipid but the maximum velocity is greatly decreased. The phosphotransfer reaction to exogenous substrates occurs in 0.5 mM ethylene bis(oxyethylenenitrilo)tetraacetic acid, although autophosphorylation in these conditions requires the presence of Ca2+. The protein kinase C inhibitor (1-(5 isoquinolinesulfonyl)-2-methylpiperazine inhibits the reaction, whereas the cAMP dependent protein kinase inhibitor is ineffective. In contrast to diacylglycerol, which is a poor activator, unsaturated fatty acids potently activate the phospholipid-free reaction. Moreover, the substrate specificity is markedly changed, e.g., myelin basic protein and histone types VI-S and VII-S appear to be relatively better substrates in the phospholipid-free reaction. The data presented indicate that protein kinase C (or some individual isoforms) may function, at least partially, without binding to membrane phospholipid and suggest that this novel characteristic of phorbol esters may account for their tumor-promoting activity. PMID- 2107969 TI - Cloning of the genes for T84.66, an antibody that has a high specificity and affinity for carcinoembryonic antigen, and expression of chimeric human/mouse T84.66 genes in myeloma and Chinese hamster ovary cells. AB - Carcinoembryonic antigen (CEA) is one of the best characterized tumor-associated antigens and is extensively used in the in vitro immunodiagnosis of human colon adenocarcinomas. Among a number of anti-CEA monoclonal antibodies, the murine monoclonal antibody T84.66 shows the highest specificity and affinity for CEA and has been used successfully for in vivo tumor imaging in mice and humans. We report here the cloning and sequencing of the genes coding for monoclonal antibody T84.66 and the amino acid sequence of the variable regions for the heavy and light chains. We also report the construction of mouse/human chimeric IgG1 antibody genes using T84.66 variable region genes and human constant region genes. The resulting chimeric gene constructs were transfected into murine myeloma cells (Sp2/0) by electroporation and into Chinese hamster ovary cells by lipofection. The chimeric antibodies obtained exhibited the same specificity and affinity for CEA as that of the T84.66 immunoglobulin produced by the murine hybridoma cell line. Antibody concentrations in culture medium supernatants were clonally variable but similar (15-480 ng/ml) for both Sp2/0 and Chinese hamster ovary transfectants; the average production by Chinese hamster ovary transfectants was only 3-5-fold less than Sp2/0 transfectants. Ascites production of Sp2/0 transfectants is sufficiently high (900 micrograms/ml) for initial in vivo studies with humanized T84.66. PMID- 2107970 TI - Contribution of aflatoxin B1 and hepatitis B virus infection in the induction of liver tumors in ducks. AB - The study of two major risk factors in the development of hepatocellular carcinoma, namely persistent hepatitis virus infection and exposure to dietary aflatoxins, has been hampered by lack of an experimental system. To this end we have used a Pekin duck model to examine the effect of congenital duck hepatitis B virus (DHBV) infection and aflatoxin B1 (AFB1) exposure in the induction and development of liver cancer. AFB1 was administered to DHBV infected or noninfected ducks at two doses (0.08 and 0.02 mg/kg) by i.p. injection once a week from the third month posthatch until they were sacrificed (2.3 years later). Two control groups of ducks not treated with AFB1 (one of which was infected with DHBV) were observed for the same period. Each experimental group included 13-16 ducks. Higher mortality was observed in ducks infected with DHBV and treated with AFB1 compared to noninfected ducks treated with AFB1 and other control ducks. In the groups of noninfected ducks treated with high and low doses of AFB1, liver tumors developed in 3 of 10 and 2 of 10 ducks; in infected ducks treated with the high dose 3 of 6 liver tumors were observed and none in the low dose of AFB1. No liver tumors were observed in the two control groups. Ducks infected with DHBV and treated with AFB1 showed more pronounced periportal inflammatory changes, fibrosis, and focal necrosis compared to other groups. All DHBV carrier ducks showed persistent viremia throughout the observation period. An increase of viral DNA titers in livers and sera of AFB1 treated animals compared to infected controls was frequently observed. No DHBV DNA integration into the host genome was observed, although in one hepatocellular carcinoma from an AFB1 treated duck, an accumulation of viral multimer DNA forms was detected. The metabolism of AFB1 in infected and noninfected duck liver was also examined. The study on the role of DHBV infection and AFB1 in the etiopathogenesis of liver tumors may help to clarify some of the basic mechanisms of carcinogenesis. PMID- 2107971 TI - Reduced suppression of plasma saturated fatty acid mobilization and oxidation by feeding in lymphoma-bearing mice. AB - Lymphoma-bearing mice have a circulating lipid-mobilizing factor, but increased plasma free fatty acid (FFA) turnover has not been demonstrable in earlier studies using postabsorptive tumor-bearing mice. We hypothesized that FFA mobilization in lymphoma-bearing mice is only elevated in fed mice and may best be observed at night (dark, reversed light cycle). AKR mice with early and advanced tumors (10(6) SL-3 lymphoma cells, i.p.) and controls were fed ad libitum (reversed light cycle, dark) or fasted 4 h (daylight, regular cycle), given injections of [14C]bicarbonate of [1-14C]palmitate-mouse serum albumin, i.v., and plasma [14C]FFA disappearance and/or breath 14CO2 were monitored. Plasma FFA mobilization, estimated by multicompartmental analysis (SAAM) of the oxidation rate was lower in fasted mice with advanced tumors [tumor, 9.5 +/- 6.0% (%SE); controls, 14 +/- 4.4% micrograms-atoms fatty acid-carbon/min/30 g body weight, n = 3 to 6 mice/time point/group]. Feeding reduced these rates 90% in control mice and 53% in mice with early tumors, but only 14% in mice with advanced tumors. Plasma FFA fractional catabolic rates were 2.5 times faster in fed mice with advanced tumors than in controls. Diminished suppression of fatty acid mobilization in fed tumor-bearing mice (at night) probably accounts partially for the body fat loss. PMID- 2107972 TI - Urokinase secretion from human colon carcinomas induced by endogenous diglycerides. AB - Colon tumor cells are more responsive to certain growth modulators in their local environment in vivo than are normal colonocytes. Examples of this class of compounds are the fecal diglycerides (DGs)(E. Friedman et al., Cancer Res., 49: 544-548, 1989), which may act as endogenous tumor promoters. At the concentration found in vivo, fecal DGs composed of oleic, myristic, and palmitic fatty acids induced mitogenesis of all classes of benign tumor cells and of half of the resected carcinomas tested in primary culture, but induced no detectable mitogenesis of normal colonocytes. Colon tumor cells also exhibit selective responses to these endogenous modulators as measured by another biological parameter, secretion of urokinase from carcinomas than from normal colonocytes. Fecal DGs also induced a 13-fold increase in urokinase mRNA synthesis in colon carcinoma cells and induced secretion of active urokinase from each of five resected carcinomas. Colon carcinomas, at both the primary site and metastatic to the liver, secreted the Mr 55,000 form of urokinase constitutively and secreted the same form upon treatment with fecal DGs. An increase in the steady-state level of urokinase secretion by saturated-chain DGs exhibited a strong dependency on the chain length of the fatty acid residues, those of 14 and 16 carbons having the greatest activity. Thus, fecal DGs composed of oleic, myristic, and palmitic acid residues induce two biological activities selectively in colon tumor cells, each of which would enhance tumor development. Selective mitogenesis would increase adenoma and carcinoma cell number relative to normal colonocyte number, and induction of the proteolytic enzyme urokinase would aid local invasion of the carcinoma within the bowel wall. PMID- 2107973 TI - Characterization of the cytolytic activity of CD4+ and CD8+ tumor-infiltrating lymphocytes in human renal cell carcinoma. AB - Previously we showed that IL2 expanded tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma mediated non-major histocompatibility complex-restricted cytotoxicity. Phenotypic analysis showed that cultured TILs were composed mostly of T-lymphocytes with varying numbers of CD4+, CD8+, and CD56+ (Leu19+) populations. Here we compared the cytolytic activity of the two predominant TIL subsets, CD3+CD4+ and CD3+CD8+, to that of the CD56+ populations. Using magnetic beads coated with antibodies to either CD4 or CD8, CD3+CD4+, and CD3+CD8+ TILs were isolated in a highly enriched form (greater than 92%) and could be expanded for over 40 days in vitro with 1000 units/ml IL2. In a 4-h 51Cr release assay the CD4+ and CD8+ TILs showed minimal lytic activity, whereas unseparated cells exhibited significant levels of non-major histocompatibility complex-restricted cytotoxicity. The lytic activity seen in the 4-h assay with unseparated TILs appeared to be related to the presence of CD56+ populations. With one exception none of the purified CD4+ or CD8+ TILs expressed any significant levels of CD56, while the unseparated TILs contained varying numbers of CD3+CD56+ and CD3-CD56+ populations. Cell-sorting experiments verified that the CD56+ populations were responsible for most of the lytic activity in 4 h even though CD3+CD56- cells represented the predominant cell type. Although CD3+CD56- TILs were minimally lytic in 4 h, we show here that both CD3+CD4+ and CD3+CD8+ subsets displayed substantial cytotoxicity in long-term assays. In the 18-h 51Cr release assay 5 of 6 CD4+ and 2 of 3 CD8+ TILs were lytic for the autologous tumor. In two cases, restimulation with the autologous tumor induced augmented cytolytic activity of TIL subsets and in one case induced lytic activity in 4 h. The cytotoxic activity of TIL subsets was further examined using a 72-h assay in which TILs were cocultured with a confluent layer of tumor cells. The degree of cytotoxicity was quantitated by measuring the amount of crystal violet dye that was incorporated by tumor cells which remained after the incubation period. CD4+ and CD8+ TILs typically caused greater than a 50% reduction of tumor cells in 3 days and the level of reduction was increased when IL2 was added to the cultures. All the CD4+ and CD8+ subset preparations were cytotoxic in the 3-day assay even though some were not lytic for certain targets in the 18-h 51Cr release assay.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2107974 TI - Comparative action of aflatoxin B1 in mammalian airway epithelium. AB - Aflatoxin B1 (AFB1) is thought to be an occupational risk factor for airway carcinogenesis where exposure to AFB1-laden grain dusts is common. Since activation of AFB1 is catalyzed by cytochromes P-450 associated with the smooth endoplasmic reticulum, we compared the response to AFB1 in cultured tracheal epithelium from species with abundant (rabbit and hamster) and scarce (rat and monkey) distributions of smooth endoplasmic reticulum in nonciliated tracheal epithelial cells. Explants from each species, incubated in medium containing 0.5 microM [14C]-AFB1 for selected intervals up to 24 h, were compared on the basis of binding of [14C]-AFB1 to tracheal DNA, amount and type of AFB1 metabolites in the medium, ultrastructurally determined population densities of epithelial cells, and distribution of bound material in epithelium as determined by autoradiographic grain densities. Cultures derived from rabbits were most active in metabolic conversion and formation of AFB1-DNA adducts, followed by those from hamsters, rats, and monkeys. Rabbit tracheal epithelium formed a significantly greater proportion of glutathione conjugates, while that from hamster formed a greater amount of AFB1-dihydrodiol, compared to rats and monkeys. The monkey formed significantly greater proportions of aflatoxin Q1 and the rabbit more aflatoxicol, compared to other species. There was selective degeneration and accumulation of labeled material in nonciliated cells in both rabbits and hamsters but not in rats or monkeys. Explants from rabbit tracheas were much more susceptible to cytotoxic injury and had higher autoradiographic grain densities than explants from hamsters. We conclude that the presence of smooth endoplasmic reticulum-containing nonciliated epithelial cells is qualitatively associated with the activation and toxicity of AFB1. PMID- 2107975 TI - Kinetics of the development of accelerated cell-cycle transit resulting from inhibition of DNA replication in the previous cycle. AB - Shortening of the generation cycle in cells in which DNA synthesis had been temporarily inhibited in the previous generation, which has been reported several times in recent years, has been confirmed in HeLa cells. As in the previous studies, the shortening is attributable to accelerated transit of G1 resulting from the accumulation, during the inhibition, of a factor needed for initiation of DNA replication. It is shown that partial (85-96%) inhibition with any one of three inhibitors is effective when the inhibitor is added in G1 or in S, but more complete (99%) inhibition is effective only if the inhibitor is added after cells have entered S. In addition, cells begin to respond to the inhibition after a lag that increases as DNA synthesis in the early part of S is progressively inhibited with aphidicolin, indicating that competence to respond is achieved only after cells have reached a particular point in the replication of their genome. PMID- 2107976 TI - Cathepsin B secretion by rabbit articular chondrocytes: modulation by cycloheximide and glycosaminoglycans. AB - Rabbit articular chondrocytes in monolayer culture are modulated away from their differentiated state and undergo morphological and biochemical changes. One of the characteristics of the modulated state is an abnormally high production of the cysteine endopeptidase cathepsin B. Addition to chondrocyte cultures of the protein biosynthesis inhibitor, cycloheximide, resulted in a concentration dependent reduction of cathepsin B secretion, which was fully restored after removal of cycloheximide. Glycosaminoglycans added to the culture medium of modulated chondrocytes partially reduced the rate of secretion of cathepsin B, this effect being dependent on their structure, the degree of sulfation, and concentration. The age of the chondrocytes and the duration of the treatment also influenced this response. The switching off of cathepsin B release was apparently best favored by a high concentration of negatively charged sulfate groups attached to a polymeric glycosaminoglycan chain; this simulates the natural environment of the chondrocytes in articular cartilage. PMID- 2107977 TI - Possible involvement of dopaminergic mechanisms in the antimigraine action of flunarizine. AB - Flunarizine, a calcium antagonist widely used in the prophylactic treatment of migraine, may interfere with dopaminergic systems. Flunarizine therapy can in fact induce extrapyramidal side effects and can increase basal as well as stimulated prolactin levels. To better define the mechanism of flunarizine action in migraine, we studied prolactin and growth hormone responses to thyrotropin releasing hormone and sulpiride in 13 female migraineurs before and after 60 days of flunarizine therapy. The treatment did not modify basal prolactin and growth hormone levels, but prolactin response to thyrotropin releasing hormone was enhanced. A paradoxical increase of growth hormone to thyrotropin releasing hormone observed before therapy was blunted after flunarizine treatment. These data indicate a modulatory action of flunarizine on dopaminergic systems which might to some extent explain the antimigraine action of this drug. PMID- 2107978 TI - Cluster headache and "dynamite headache": blood flow velocities in the middle cerebral artery. AB - Nitroglycerin (NG) induces in cluster headache patients and controls an increase in systemic diastolic blood pressure and/or heart rate and a decrease in blood flow velocity in the middle cerebral artery (VMCA). Termination of NG induced cluster headache-like attack was correlated to an increase of VMCA compared to the VMCA before NG administration (p less than 0.01). This increase was not found in patients without attack or in controls. The NG induced "dynamite headache" in the controls subsided when blood pressure and heart rate were normalized, but the decrease of VMCA still prevailed. Orbital phlebograms have shown pathologic changes in cluster headache and in Tolosa-Hunt syndrome but not in controls. Ocular sympathetic nerves are involved in cluster headache but seldom in Tolosa Hunt syndrome. It is suggested that the start of a cluster headache attack is due to an increase and the termination of the attack to a decrease of blood flow to the sympathoplegic phlebopathic cavernous sinus. PMID- 2107979 TI - Systemic and local saphenous vein graft thrombolysis using a tissue plasminogen activator. AB - Many studies are currently evaluating the potential role of thrombolytic therapy in patients with ischemic syndromes who have undergone previous coronary artery bypass grafting. Limited experience has been published regarding the use of local urokinase and streptokinase infusions and the use of systemic recombinant tissue type plasminogen activator as thrombolytic agents in patients with previous coronary artery bypass surgery. To date, however, there has been no published experience regarding the use of recombinant tissue-type plasminogen activator (rt PA) either systemically or locally in the post-bypass patient where angiographic demonstration of aortocoronary saphenous vein graft obstruction was available pre and post-therapy. Similarly there has been no previous report of the use of rt PA infused locally to recanalize an occluded aortocoronary saphenous vein graft. This report describes successful thrombolysis and subsequent balloon angioplasty of saphenous vein grafts with angiographically documented thrombus using systemic and local rt-PA infusion. PMID- 2107980 TI - C-factor: a cell-cell signaling protein required for fruiting body morphogenesis of M. xanthus. AB - During fruiting body development, the product of the csgA gene is necessary for cellular aggregation, for spore differentiation, and for gene expression that is initiated after 6 hr of starvation. From nascent wild-type fruiting bodies we have purified a polypeptide of 17 kd called C-factor, which, at approximately 1 to 2 nM, restores normal development to csgA mutant cells. C-factor activity is not recovered from extracts of unstarved, growing cells or csgA mutant cells. The amino acid sequence from purified C-factor demonstrates that it is the product of the csgA gene. C-factor is active over a narrow range of concentration and has properties of a morphogenetic paracrine signal. PMID- 2107981 TI - The HOP1 gene encodes a meiosis-specific component of yeast chromosomes. AB - The HOP1 gene in Saccharomyces cerevisiae is important for meiotic chromosomal pairing, because hop1 diploids fail to form synaptonemal complex during meiosis and are defective in crossing over between, but not within, chromosomes. We demonstrate here that the HOP1 gene is transcriptionally regulated during sporulation and that the HOP1 protein is situated along the lengths of meiotic chromosomes. Furthermore, the HOP1 protein contains a Cys2/Cys2 zinc finger motif. A mutation within this motif that changes a cysteine to serine results in the hop1 phenotype, consistent with the possibility that the HOP1 gene product acts in chromosome synapsis by directly interacting with DNA. These observations demonstrate that HOP1 encodes a component of meiotic chromosomes, perhaps serving as a constituent of the synaptonemal complex. PMID- 2107982 TI - The Drosophila 74EF early puff contains E74, a complex ecdysone-inducible gene that encodes two ets-related proteins. AB - We have isolated an ecdysone-inducible gene, E74, from the early puff at position 74EF in the Drosophila polytene chromosomes. We show that E74 consists of three nested transcription units that derive from unique promoters but share a single polyadenylation site. The 60 kb E74A unit is directly induced by ecdysone and leads to the synthesis of a 6.0 kb mRNA that contains an unusually long 5' leader (1891 nucleotides) with 17 short ORFs. Within the fifth of the seven E74A introns are two E74B promoters that direct the synthesis of 4.8 and 5.1 kb mRNAs. The nested arrangement of these transcription units leads to the formation of two E74 proteins, each with a unique N-terminal domain joined to a common C-terminal domain. The unique N-terminal domains contain regions rich in acidic amino acids while the C-terminal domain is rich in basic amino acids and is very similar to proteins encoded by the ets proto-oncogene superfamily. PMID- 2107983 TI - Lymphocyte migration into brain modelled in vitro: control by lymphocyte activation, cytokines, and antigen. AB - Factors controlling lymphocyte adhesion to brain endothelium were investigated in vitro. Mitogen activation of lymphocytes causes increased adhesion to endothelium, which is maximal at 7-24 hr, declines to normal levels after the cells divide, and requires protein synthesis. Rat brain endothelium can be stimulated with IFN-gamma to increase its adhesion to either normal or activated lymphocytes. The endothelium is sensitive to low levels of cytokine: adhesion develops rapidly after stimulation and requires new protein synthesis. Antigen specific line cells also adhere more effectively to endothelium than normal lymph node cells. This is enhanced by IFN-gamma treatment of the endothelium and is further increased marginally in the presence of the cognate antigen. The results suggest that either local stimulation of endothelium with cytokines or lymphocyte activation in the periphery will modulate lymphocyte traffic into brain. PMID- 2107984 TI - Role of thromboxane A2 in the cardiovascular response to intracoronary C5a. AB - Intracoronary administration of complement component C5a induces transient decreases in coronary blood flow and regional left ventricular segment shortening, associated with intramyocardial granulocyte trapping. We evaluated the influence of a cyclooxygenase inhibitor (acetylsalicylic acid, n = 8) or a thromboxane A2/prostaglandin H2 receptor antagonist (SQ29548, n = 6) on these C5a induced cardiovascular responses. Open-chest anesthetized pigs were instrumented to monitor heart rate, arterial blood pressure, left anterior descending coronary blood flow, regional left ventricular segment shortening, and dP/dt. Oxygen content, lactate concentration, leukocyte count, and thromboxane B2, the stable metabolite of thromboxane A2, were measured in arterial and regional coronary venous blood. Repetitive injections of intracoronary C5a (500 ng) given 60 minutes apart showed no tachyphylaxis of the hemodynamic response. However, tachyphylaxis was seen in coronary blood flow changes when injections were spaced 30 minutes apart. An increase in myocardial oxygen extraction and lactate production was observed after intracoronary C5a. Administration of acetylsalicylic acid (50 mg/kg i.v.) attenuated C5a-induced decreases in coronary blood flow (-8 +/- vs. -3 +/- 1 ml/min) and regional left ventricular segmental shortening (-10 +/- 3% vs. -2 +/- 1%) and blocked the maximal increase in coronary venous thromboxane B2 (2.0 +/- 0.1 vs. 0.2 +/- 0.1 pmol/ml plasma). Furthermore, SQ29548 (30 micrograms/kg/min) reduced C5a-induced changes in coronary blood flow (-13 +/- 2 vs. -4 +/- 2 ml/min) and segmental shortening (-14 +/- 2% vs. -3 +/- 1%). Neither cyclooxygenase inhibition nor thromboxane A2/prostaglandin H2 antagonism blocked the decrease in coronary venous granulocyte count.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2107985 TI - The safety of intravenous dipyridamole thallium myocardial perfusion imaging. Intravenous Dipyridamole Thallium Imaging Study Group. AB - Clinical data on 3,911 patients were collected from 64 individual investigators to evaluate the safety of intravenous dipyridamole-thallium imaging as an alternative to exercise thallium imaging for the evaluation of coronary artery disease. There were two deaths because of myocardial infarctions, two nonfatal myocardial infarctions, and six cases of acute bronchospasm. Chest pain occurred in 770 patients (19.7%). Headache and dizziness were reported by 476 patients (12.2%) and 460 patients (11.8%), respectively. ST-T changes on the electrocardiogram were seen in 292 patients (7.5%). Use of parenteral aminophylline to treat adverse events associated with intravenous dipyridamole brought complete relief of symptoms in 439 of 454 patients (96.7%). There is a potential for increased risk for serious ischemic events in patients with a history of unstable angina who are administered intravenous dipyridamole. In patients with acutely unstable angina (i.e., continuing chest pain) or in the acute phase of myocardial infarction, use of intravenous dipyridamole in thallium scintigraphy should be avoided. There is also an increased risk for bronchospasm in patients with a history of asthma; acute bronchospasm can be relieved immediately by administration of aminophylline. These results demonstrate that intravenous dipyridamole-thallium scintigraphy is a relatively safe, noninvasive technique for the evaluation of coronary artery disease. PMID- 2107986 TI - Augmented and sustained plasma concentrations after intramuscular injections of molecular variants and deglycosylated forms of tissue-type plasminogen activators. AB - We have previously explored induction of coronary thrombolysis with tissue-type plasminogen activator (t-PA) administered intramuscularly. Absorption-enhancing agents that rendered the approach feasible were identified, but large amounts of activator were required and initial elevations of concentrations in plasma could not be sustained. The present study was designed to determine whether more therapeutically favorable plasma concentrations could be induced by genetically engineering or chemically modifying t-PA to prolong its half-life based on the hypothesis that the ratio of absorption to clearance would be increased. Each of four genetically engineered variants (one variant with growth factor and kringle 1 domains deleted and kringle 2 duplicated, a second variant with a cysteine for Arg substitution in the growth factor domain, a third variant with an additional urokinase kringle inserted, and a fourth variant with the growth factor domain deleted) and enzymatically deglycosylated t-PA exhibited prolonged half-life after bolus intravenous injection in rabbits. Each elicited substantially higher and more sustained elevations in plasma after intramuscular injection in rabbits or dogs with absorption-enhancing agents as compared with wild-type t-PA that were not accompanied by a systemic lytic state. Thus, use of molecular variants of t-PA with prolonged half-lives in the circulation permits induction of augmented and sustained elevations of plasma concentrations after intramuscular injection with absorption-enhancing agents as compared with wild-type t-PA, rendering potentially therapeutic blood levels more attainable with relatively modest amounts of material. PMID- 2107987 TI - A fluorimetric enzyme assay for the diagnosis of Morquio disease type A (MPS IV A). AB - 4-Methylumbelliferyl-beta-D-galactopyranoside-6-sulphate was synthesized and used for the determination of galactose-6-sulphate sulphatase activity. Fibroblasts and leucocytes from 12 different Morquio A patients, showed 0.0-2.7% of mean normal galactose-6-sulphate sulphatase activity. Heterozygotes showed intermediate activities. The enzymatic liberation of the fluorochrome from 4 methylumbelliferyl-beta-D-galactopyranoside-6-sulphate requires the sequential action of galactose-6-sulphate sulphatase and beta-galactosidase. Normal beta galactosidase activity caused nearly complete hydrolysis of non-fluorescing 4 methylumbelliferyl-galactoside, formed during incubation. In cell extracts with a beta-galactosidase deficiency however, a second incubation in the presence of excess beta-galactosidase is needed to avoid underestimation of galactose-6 sulphate sulphatase activity. PMID- 2107988 TI - Elevation of hormone-binding globulins in acute intermittent porphyria. AB - Sex hormone-binding globulin (SHBG), thyroxine-binding globulin (TBG) and cortisol-binding globulin (CBG) were measured in plasma of 26 patients with acute intermittent porphyria (AIP). Twelve patients had clinically manifest disease and all had elevated SHBG levels. All but one of 14 patients with latent porphyria had normal SHBG levels. TBG was elevated in 9 of the patients with clinically manifest porphyria and CBG elevated in three. Levels of TBG and CBG were either normal or only slightly elevated in those with latent porphyria. In a prospective study of 30 attacks of AIP in 7 patients, SHBG levels fell between admission and discharge, the fall being significant in the group of 21 attacks treated with haem arginate (p less than 0.001). Our findings suggest that a close correlation exists between elevated SHBG and clinical expression of AIP. PMID- 2107989 TI - The effect of gold sodium thiomalate and auranofin on lipopolysaccharide-induced interleukin-1 production by blood monocytes in vitro: variation in healthy subjects and patients with arthritis. AB - The anti-rheumatic gold compounds gold sodium thiomalate (GST) and auranofin (AF) have variable and often unpredictable effects in patients treated for arthritis. As inhibition of interleukin-1 (IL-1) production may be an important effect of these drugs, we investigated their effect on IL-1 production by lipopolysaccharide (LPS) stimulated monocytes in a serum-free, non-adherent culture system. A bi-modal effect was observed: low concentrations (GST 10-250 ng/ml and AF 1-100 ng/ml) potentiated IL-1 production, and higher concentrations (GST 200-1000 ng/ml and AF10-500 ng/ml) inhibited it. This bi-modal effect was observed for both secreted and cell-associated IL-1 activity with the exception that GST failed to inhibit cell-associated IL-1 generation. The potentiating effect was dependent on the continuous presence of gold for at least the first few hours after LPS stimulation. The inhibitory effect of GST was dependent on its presence after LPS stimulation while that of AF was evident even if cells were pretreated with AF and washed before exposure to LPS. There was considerable individual variation in IL-1 production in response to LPS as well as in the effects of gold on cells from both healthy individuals and patients with arthritis. There was also some overlap in the range of concentrations of gold that potentiated and inhibited IL-1 production, and there was relative insensitivity to the inhibitory effects of gold in certain individuals. These results may explain some of the variability in the response of patients to chrysotherapy and support further studies to see if these in vitro effects might predict clinical response to gold. PMID- 2107990 TI - Naturally occurring human IgG antibodies to intracellular and cytoskeletal components of human platelets. AB - Immunoblotting of platelets that have been subjected to SDS-PAGE has revealed that sera from normal individuals contain IgG which binds to many platelet components. This binding was seen with autologous and heterologous platelets using serum of males and of nulliparous females who had not received blood transfusions. Although binding patterns of different sera were not identical, almost all sera caused IgG binding to platelet components of 87-90 kD, 140 kD (identified as vinculin) and 220-240 kD (tentatively identified as talin and actin-binding protein). Purified IgG showed the same binding pattern as whole serum and F(ab')2 fragments retained their ability to bind to many components. The titre of IgG binding in serum was 1:50-1600 while that of alloantibodies to the PlA1 antigen was 1:3200. IgG binding components were not secreted when platelets were stimulated and were rarely associated with isolated membranes, but were located either in platelet cytoplasm or cytoskeletons. IgG binding was decreased by absorbing sera with lysed platelets or isolated cytoskeletons, but only slightly with intact platelets. Microaffinity purification of IgG which formed a major band on immunoblots showed that it was antibody with specificity for vinculin or its degradation products. These findings suggest that normal sera contain naturally occurring IgG antibodies with specificity for intracellular platelet antigens and that in some cases their titre approaches that of antibodies of pathological significance. PMID- 2107991 TI - Evidence that defective interferon-gamma production in atopic dermatitis patients is due to intrinsic abnormalities. AB - The in vitro production of interferon-gamma (IFN-gamma) in 19 atopic dermatitis (AD) patients was compared with that of 12 controls. IFN-gamma production by phytohaemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC) was profoundly diminished in AD patients, whereas the proliferative response was similar to that of control PBMC. The addition of 40 U/ml of interleukin-2 (IL-2) to the cultures failed to restore IFN-gamma production. Similarly, removal of adherent cells also had no effect. Reduced IFN-gamma secretion was observed after stimulation with the CD3 monoclonal antibody OKT3, ionomycin + 12-O-tetradecanoyl phorbol-13-acetate (TPA) or with high levels of IL-2 (200 U/ml). There were increased proportions of CD4+ T helper/inducer cells and decreased proportions of CD8+ T cytotoxic-/suppressor cells and CD16+ natural killer (NK) cells in AD patients. This resulted in an increased CD4/CD8 ratio as compared with controls, but no correlation was observed between numbers of T cell subpopulations and IFN gamma generation. However, a significant correlation was found between IFN-gamma generation in vitro and IgE serum concentration in AD patients. The data suggest that the decreased production of IFN-gamma by AD patients is due to intrinsic differences in capacity to produce this cytokine and is not the result of differences in regulatory cell interactions. Moreover, the findings indicate that decreased production of IFN-gamma may be an important factor in the pathogenesis of this disease. PMID- 2107992 TI - The inductive effect of interleukin-4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes. AB - Using murine monoclonal antibodies against human IgG subclasses, specific and sensitive ELISAs assay to quantify the four human IgG subclasses in cell culture supernatants were established. The effect of human recombinant interleukin-4 (IL 4) on the regulation of IgG subclasses by normal peripheral blood lymphocytes was investigated. In addition to the enhancement of IgE synthesis, IL-4 preferentially induced IgG4 synthesis in vitro, whereas IL-4 had no effect on IgG1, IgG2, and IgG3 synthesis. IL-4-induced IgG4 production was blocked in a dose-dependent manner by recombinant interferon-gamma and anti-human IL-4 monoclonal antibody. Collectively, this data indicates that IL-4 plays an important regulatory role in both IgG subclass and IgE synthesis. PMID- 2107993 TI - Enhancement of experimental metastatic ability by tumor necrosis factor-alpha alone or in combination with interferon-gamma. AB - The effects of recombinant tumor necrosis factor-alpha (TNF-alpha) and interferon gamma (IFN-gamma) on B16 mouse melanoma experimental metastatic ability and major histocompatibility complex (H-2b) antigens expression were studied. B16 cells exposed in vitro to TNF-alpha had an increased H-2 expression and were more metastatic than untreated cells. The simultaneous treatment with TNF-alpha and IFN-gamma amplified the enhancement of experimental metastasis and all other effects obtained with TNF-alpha alone. The B16 clone B78H1, selectively resistant to H-2 induction and to enhancement of metastatic ability by IFN-gamma, was not affected by treatment with TNF-alpha and with TNF-alpha + IFN-gamma. These findings contribute to a better understanding of the pleiotropic effects of TNF, some of which can have opposing actions in the complex tumor-host relationships. PMID- 2107994 TI - Prophylaxis with systemic antibiotics versus gentamicin bone cement in total hip arthroplasty. A five-year survey of 1688 hips. AB - In Sweden in 1976, nine orthopedic departments organized a prospective, randomized, and controlled study in which the prophylactic effect of systemic antibiotics (SA) was compared to gentamicin bone cement (GBC) in 1688 consecutive total hip arthroplasties (THAs). After a follow-up period of one to two years, there was a statistically significant difference in the infection rate between the two groups in favor of the gentamicin cement. After five years or more, the difference was unaltered. Altogether, 16 deep infections had occurred in the SA group (1.9%) and seven (0.8%) in the GBC group. Roentgenographically, aseptic loosening had occurred in 29% and 24% of the hips in the SA and GBC groups, respectively, which suggests that admixture of the antibiotic did not weaken the cement. The results of this five-year review clearly showed the prophylactic value of gentamicin cement against deep infection after THA but did not support the hypothesis that this effect was prolonged over one year. PMID- 2107995 TI - CO2 laser cauterization of giant-cell tumor margins. AB - The CO2 laser was evaluated to determine its effectiveness for marginal cauterization of giant-cell tumors after resectional curettage. Average power densities of 11-53 W/cm2 for corresponding application times of 120 and 60 seconds were found to produce 30 degrees temperature rises in fresh human femoral heads. This temperature was adequate to achieve thermal necrosis of the tumor margins to a depth of 5 mm. CO2 laser resection was found to be accurate and reproducible. No damage to underlying hyaline cartilage and soft tissues was evident histologically at one and four weeks after experimental local laser cauterization of distal femoral condyles in rabbits. PMID- 2107996 TI - Sequential ventilation/perfusion imaging of massive pulmonary embolism treated with recombinant tissue plasminogen activator. AB - Pulmonary embolism is a common clinical problem estimated to cause 200,000 deaths per year in the United State. There is increasing interest in early diagnosis and prompt aggressive therapy. A case is reported of a patient with massive pulmonary embolism treated with recombinant tissue plasminogen activator. Ventilation/perfusion imaging was used both to make an early diagnosis as well as to evaluate the efficacy of therapy. PMID- 2107997 TI - Ifosfamide and mesna. AB - The chemistry, pharmacology, pharmacokinetics, and adverse effects of ifosfamide and mesna are described separately, followed by a discussion of the adverse effects of concurrent ifosfamide and mesna, the clinical spectrum of ifosfamide, and the dosage and administration of the two drugs. Ifosfamide, an active analogue of cyclophosphamide, differs from other direct alkylating substances in that it requires biotransformation in the liver before it can exert its alkylating effects. The bioavailability of ifosfamide after oral administration exceeds 95%. The adverse effects of ifosfamide include hematologic, urinary tract, GI tract, and CNS toxicity. Mesna is a thiol compound designed to function as a regional detoxificant of urotoxic oxazaphosphorine cytostatics such as ifosfamide. The drug is rapidly oxidized in the plasma to its dimeric form, dimesna, one third of which is converted back to mesna by glutathione reductase. The mean total urinary availability of mesna administered orally is 76%. Mesna may produce gastrointestinal and allergic reactions. The adverse effects of concurrent ifosfamide and mesna include urinary tract and renal toxicity. Although current FDA-approved labeling is limited to refractory germ cell testicular cancer, ifosfamide has also shown efficacy in the treatment of lymphoma, lung cancer, and sarcomas. Optimum dosage and scheduling remain to be determined; studies suggest that a fractionated dosage schedule provides antineoplastic activity with tolerable toxicity. Ifosfamide, used in combination with mesna for uroprotection, provides a useful therapeutic option for the management of patients with testicular cancer, soft tissue sarcomas, or high grade malignant lymphomas. PMID- 2107998 TI - Cost-effective management of leg ulcers. PMID- 2107999 TI - Use of capnography in diagnosis of pulmonary embolism during acute respiratory failure of chronic obstructive pulmonary disease. AB - In chronic obstructive pulmonary disease (COPD) patients, there is a difference between PaCO2 and end-tidal partial pressure of CO2 (PetCO2). This gradient P(a et)CO2 is due to ventilation/perfusion mismatching and deadspace, and is usually abolished by forced and prolonged expiration. We hypothesized that this gradient might not be canceled by forced expiration in the case of acute respiratory failure (ARF) related to pulmonary embolism (PE). Forty-four adult COPD patients were prospectively entered into this study; they were suspected of having ARF related to PE on the basis of clinical and biological data on admission. Maximum expired partial pressure of CO2 (PemCO2) was measured in mechanically ventilated and sedated patients by an interrupt of mechanical support. CO2 concentration was recorded during the following prolonged and passive expiration. The test was considered valid if an expiratory plateau was obtained. PemCO2 was measured in triplicate. Simultaneously, PaCO2 was measured and the ratio, R = [( 1 PemCO2]/PaCO2) x 100, was calculated. Pulmonary angiography was performed on the same day for all patients. Results showed that 17 patients had PE (PE+) and 17 had no PE (PE-). The two groups were comparable regarding mean age, severity of underlying chronic respiratory disease, PaCO2, PaO2, and hemodynamic data on admission. P(a-em)CO2 and R were significantly different in PE+ and PE- patients at 12 +/- 6.9 torr compared to 1 +/- 2.4 torr and at 28 +/- 14.8% compared to 2 +/- 6.2% (p less than .001), respectively. The positive predictive value of the test was 74%, but the negative predictive value 100% and the specificity was 65%, but sensitivity was 100%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108000 TI - Prediction of outcome of cardiopulmonary resuscitation from end-tidal carbon dioxide concentration. AB - Capnography is a valuable tool in the management of cardiac arrest, since end tidal CO2 (PetCO2) correlates well with cardiac output and there are no other suitable noninvasive ways to measure this important variable during resuscitation. Animal studies also suggest that PetCO2 correlates well with the likelihood of resuscitation, but this has never been confirmed in humans. We prospectively studied 55 adult, nontraumatic prehospital cardiac arrest patients. PetCO2 was monitored with an in-line sensor on arrival in the ED and throughout the arrest, which was managed by the usual advanced cardiac life-support treatment guidelines. Chest compression was carried out mechanically. Patients were assessed for return of spontaneous pulse as evidence of initial resuscitation; hospital discharge and long-term survival were not examined. Fourteen patients developed spontaneous pulses and were resuscitated, and 41 were not. The length and aggressiveness of treatment and CPR were not different between the two groups, nor were there differences in down time, resuscitation time, or other factors known to affect outcome. Patients who developed a pulse had a mean PetCO2 of 19 +/- 14 (SD) torr at the start of resuscitation, and those who did not had a mean PetCO2 of 5 +/- 4 torr (p less than .0001). This difference was significant both in nonperfusing rhythms (asystole and ventricular fibrillation) and in potentially perfusing rhythms (electromechanical dissociation). An initial PetCO2 of 15 torr correctly predicted eventual return of pulse with a sensitivity of 71%, a specificity of 98%, a positive predictive value of 91%, and a negative predictive value of 91%. A receiver operating curve was generated for sensitivity and specificity of the test at varying PetCO2 thresholds. PMID- 2108001 TI - Response of tissue oxygenation to systemic hyperoxia after cardiac surgery. AB - The opening of the peripheral circulation was studied in eight patients in the immediate postoperative phase after coronary artery bypass grafting. The patients were coupled to a respirator, and the FIO2 was maintained at 0.3 except for two 30-min periods of ventilation with 100% oxygen. Oxygen exposures occurred 1 and 8 h after ICU admission. Transcutaneous PO2 (PtcO2), subcutaneous PO2 (PscO2), laser-Doppler skin red cell flux (RCF), and peripheral skin temperature (Tft) were recorded continuously in the upper extremity. The opening of peripheral circulation was reflected as an increase of cardiac index and a decline of mean arterial pressure and systemic vascular resistance. Concurrently, the Tft, PscO2, and RCF rose clearly, whereas the PtcO2 remained unchanged. During both periods of oxygen ventilation, the PaO2 similarly rose and was closely followed by an increase in PtcO2. The PscO2 showed no response to the first period of systemic hyperoxia, but increased promptly during the second exposure to oxygen. To summarize, peripheral tissue oxygenation in postoperative cardiac patients cannot be efficiently elevated by systemic hyperoxia until the peripheral vascular bed is opened. PMID- 2108002 TI - Five percent human albumin in lactated Ringer's solution for resuscitation from hemorrhagic shock: efficacy and cardiopulmonary consequences. AB - Using an ovine model of acute hemorrhagic shock, we evaluated the utility of 5% albumin in lactated Ringer's (5% ALR) solution as a resuscitation solution. After instrumentation and obtaining baseline values for BP, mean arterial pressure (MAP), pulmonary capillary wedge pressure (WP), CVP, cardiac output, extravascular lung water (EVLW), and blood gases (mixed venous and arterial), animals were rapidly exsanguinated to an MAP of 50 mm Hg. After 30 min at this pressure, measurements were repeated and 5% ALR was administered until two of three variables (WP, MAP, cardiac output) were restored to baseline values. The administration of 5% ALR was continued as needed to maintain baseline values of these variables. Sixty minutes later, data were again recorded. For induction of shock, 15.7 +/- 5.2 ml of blood/kg body weight was removed. Pulmonary artery pressure, WP, MAP, and cardiac output all significantly decreased with shock. After resuscitation, all values except MAP returned to baseline. The resuscitation volume of 5% ALR was 25.2 +/- 18.4 ml/kg. There were no changes in EVLW or intrapulmonary shunt. Oxygen delivery was significantly compromised during shock but returned to baseline after resuscitation. We conclude that in a model such as ours, 5% ALR can reverse the hemodynamic effects of acute hemorrhagic shock. PMID- 2108003 TI - Correlation between cardiopulmonary changes and severity of acute lung injury in dogs. AB - In an attempt to determine the physiologic parameters that best correlate with severity of lung edema (wet/dry [W/D] weight), we serially monitored multiple cardiopulmonary hemodynamics, airway pressure, and blood gases on both 100% oxygen and room air after graded infusions of oleic acid (OA) in dogs. We found significant increases in the intrapulmonary shunt fraction (Qsp/Qt), mean pulmonary arterial pressure (MPAP), pulmonary (PVR) and systemic vascular resistance (SVR), alveolar-arterial PO2 difference (P[A-a] O2), and peak airway pressure (Paw), but decreases in PaO2 and pH. These cardiopulmonary hemodynamic changes were similar to those found in adult respiratory distress syndrome (ARDS). This study showed that Qsp/Qt (r = .72, p less than .001), PaO2 (r = .60, p less than .01), P(A-a)O2 (r = .55, p less than .01), pH (r = -.55, p less than .01), MPAP (r = .50, p less than .05) and Paw (r = .49, p less than .05) significantly correlated linearly with W/D. The significant correlation is not high enough clinically to predict the severity of acute permeability pulmonary edema considering only one parameter of cardiopulmonary hemodynamic change. Therefore, we propose the possible prediction of the severity of ARDS by considering all of the above hemodynamic changes together with Paw or dynamic compliance. PMID- 2108004 TI - Tracheal obstruction after emergency tracheostomy in a patient with a postpartum factor VIII inhibitor. PMID- 2108005 TI - Essential amino acid-induced adult hyperammonemic encephalopathy and hypophosphatemia. PMID- 2108006 TI - Immediate resuscitation. PMID- 2108007 TI - Lower esophageal sphincter pressure in Chagas' disease. AB - It is known that lower esophageal sphincter (LES) pressure in patients with idiopathic achalasia is higher than in normal subjects, but in patients with Chagas' disease, who have esophageal disease with similar clinical, manometric, and radiologic results, studies of LES pressure show contradictory findings. We measured the LES pressure in 118 patients with chronic Chagas' disease, 14 patients with idiopathic achalasia, and 50 control subjects using a perfused catheter and the stationary pull-through (SPT) technique. The patients with Chagas' disease had normal esophageal radiologic examination (group A, N = 50), delay in esophageal clearance without dilatation (group B, N = 41), or delay in esophageal clearance with dilatation (group C, N = 27). The LES pressure of Chagas' disease patients of group A (18.6 +/- 9.1 mm Hg, mean +/- SD), group B (17.8 +/- 9.7 mm Hg), and group C (21.6 +/- 10.1 mm Hg) was lower (P less than 0.001) than the LES pressure of the controls (24.9 +/- 10.2 mm Hg). In patients with idiopathic achalasia, the LES pressure (40.7 +/- 17.8 mm Hg) was higher than in control subjects (P less than 0.01) and Chagas' disease patients (P less than 0.001). We conclude that the LES pressure of patients with Chagas' disease tended to be lower than that of control subjects and achalasia patients. PMID- 2108008 TI - Percutaneous carbon dioxide excretion in the newborn infant. AB - Percutaneous carbon dioxide excretion was studied in 42 newborn infants between 25 and 39 weeks gestation, using a closed skin cell attached to the abdomen. The rate of excretion during the first few days of life was inversely related to gestation, increasing from a mean of 31 ml/m2/h at term to 198 ml/m2/h below 30 weeks gestation. Postnatally there was a rapid fall in the rate of excretion in very preterm infants to values about twice those found at term. The rate of excretion was linearly related to the CO2 diffusion gradient, and zero diffusion would be expected when there was no diffusion gradient. It is estimated that up to 15% of resting CO2 excretion occurs through the skin of very preterm infants, and more if the tissue PCO2 is elevated. PMID- 2108009 TI - Immunoneutralization of circulating inhibin in the hypophysiotropically clamped male rhesus monkey (Macaca mulatta) results in a selective hypersecretion of follicle-stimulating hormone. AB - The purpose of this experiment was to examine directly whether inhibin is involved in the testicular regulation of FSH secretion in the male rhesus monkey. To this end, the pituitary-testicular axis in eight juvenile monkeys was prematurely activated by a chronic iv infusion of GnRH (0.1 microgram/min for 3 min every 3 h). After a minimum of 5 weeks of pulsatile GnRH stimulation, four animals received a brief (30-min) iv infusion of an ovine antiserum to inhibin alpha-subunit (approximately 10 ml/kg BW), and four monkeys received a comparable volume of a control ovine immune serum. The pulsatile GnRH infusion continued without interruption throughout the entire experiment. The FSH response to passive immunization against inhibin was determined by measuring concentrations of this gonadotropin in sequential plasma samples collected immediately before a GnRH infusion and for 3 h thereafter (an inter-GnRH pulse interval) on days 0.5, 1, 2, 4, 8, and 16 after injection of the immune serum. Administration of the antiserum to inhibin alpha-subunit resulted, within 2 days, in a 2- to 3-fold increase in the mean concentration and pulse amplitude of plasma FSH. The hypersecretion of FSH induced by administration of the antiserum to inhibin alpha subunit was maintained until day 4, and then mean concentrations and mean pulse amplitudes of plasma FSH declined, reaching preantibody control levels by day 16. The time course of the antiserum-induced hypersecretion of FSH was closely correlated to changes in circulating inhibin-binding activity. Most importantly, the hypersecretion of FSH observed during the first 2 days after immunoneutralization of circulating inhibin was indistinguishable from that elicited during the initial 2 days after subsequent bilateral orchidectomy and concomitant testosterone (T) replacement. Administration of a control immune serum did not influence circulating FSH concentrations, and neither the antiserum to inhibin alpha-subunit nor the control immune serum induced changes in pituitary LH secretion and testicular T release. Since the exogenous drive to the pituitary-testicular axis of the animals was clamped in a mode that produced a pattern of pulsatile LH and T secretion comparable to that observed in adult monkeys, the present findings provide evidence for the view that inhibin plays a major role in the testicular regulation of FSH secretion during adulthood by exerting a selective inhibition on the secretion of this gonadotropin directly at the level of the anterior pituitary gland. PMID- 2108010 TI - Detection of a 58-kilodalton high density lipoprotein-binding protein in the membrane fraction of luteinized rat ovaries. AB - The membrane fraction from the ovaries of pseudopregnant rats exhibits specific, high affinity binding of high density lipoproteins (HDL). Previous studies have indicated that HDL binding in this tissue is up-regulated by hCG and may be involved in supplying cholesterol as substrate for steroid hormone production. To characterize the HDL-binding activity, we solubilized the membrane proteins using 40 mM beta-octylglucoside and then separated them by electrophoresis on a 7% sodium dodecyl sulfate-polyacrylamide gel. The separated proteins were transferred to nitrocellulose sheets and subsequently incubated in the presence of [125I]apolipoprotein-E-free HDL. Autoradiography of the nitrocellulose revealed that the labeled HDL was bound to a single major band, with an apparent mol wt of 58,000 daltons. Neither reduction with beta-mercaptoethanol nor heat denaturation before separation on the gel affected the molecular size of the band, which indicates that it is probably a single polypeptide chain. The band was up-regulated in this tissue by in vivo treatment with 25 IU hCG in a time dependent manner similar to the up-regulation of [125I]HDL-binding activity. In contrast to the binding of low density lipoprotein (LDL) to its receptor, the binding of HDL is independent of Ca+2. Incubation of the transferred proteins in the presence of [125I] Incubation of the transferred proteins in the presence of [125I]apolipoprotein-E-free HDL and either 5 mM CaCl2 or 15 mM EDTA had no effect on the appearance of the 58-kDa band. Furthermore, ligand blotting in the presence of a 100-fold excess of LDL did not affect the appearance of the band, whereas a 100-fold excess of apoliprotein-E-free HDL caused the disappearance of the band, indicating specificity for binding of HDL. Treatment of the sample with trypsin before electrophoresis also caused the band to disappear, revealing the protein nature of the band. These experiments indicate that the HDL receptor in luteinized rat ovaries is a 58,000-dalton protein. PMID- 2108011 TI - Castration induces time-dependent changes in the follicle-stimulating hormone beta-subunit messenger ribonucleic acid-containing gonadotrope cell population. AB - We have previously observed 3- to 10-fold increases in pituitary LH beta-subunit mRNA levels in the rat 28 days after castration. These changes correlate with increases in percentages and areas of cells that bear the LH beta mRNA and with the amount of label for mRNA per cell. In contrast, FSH beta mRNA levels increase 2.5- to 4-fold 7-14 days after castration, decline to near-intact levels 28 days postcastration, and rise 4.5-fold by 96 days postcastration. The purpose of this study was to determine morphological correlates of these changes in FSH beta mRNA levels. Dispersed pituitary cells from intact and castrated rats were analyzed for FSH beta and LH beta mRNAs and protein by in situ hybridization techniques and immunocytochemistry, respectively. In intact animals over 79% of pituitary cells labeled for FSH beta mRNA were small (area less than 150 microns 2). However, 7 days after castration, the average area of labeled cells increased 4 fold (80% were over 200 microns 2 in area), without a significant change in percentages of FSH beta mRNA-containing cells. The amount of mRNA per cell (as measured by area of label per cell) increased 6-fold. Fourteen days after castration, the average area of cells containing FSH beta mRNA decreased to 2 times that in intact rats (48% were greater than 200 microns 2). The percentage of labeled cells increased from 11% (intact) to 20%. Furthermore, the dual labeling studies showed that 37% of these FSH cells were monohormonal (detected by FSH beta mRNA, but not LH beta antigen) compared with 23% in intact rats. At this same time, the FSH cells exhibited a decrease in the amount of mRNA per cell. In 21- to 84-day castrates, average areas of FSH beta mRNA remained at 2 2.5 times the areas of cells from intact rats. In addition, 21 days after surgery the percentages of labeled cells and amount of FSH beta mRNA per cell declined to those in intact rats. A greater proportion was multihormonal (only 15% expressed FSH beta mRNA but not LH beta antigens). At 84 days there were 2-fold increases in the percentages of labeled cells and the density of label, which correlate with the recovery in mRNA levels assayed at 96 days. Thus, factors that contribute to the early rise in FSH beta mRNA include increases in the amount of mRNA per cell, which coincides with increased cell area.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2108012 TI - Molecular biology of the pituitary gonadotropins. PMID- 2108013 TI - Recent achievements in studies on thyroid hormone-binding proteins. PMID- 2108014 TI - Subcortical metabolic alterations in partial epilepsy. AB - The function of subcortical nuclei in partial epilepsy was investigated using positron emission tomography (PET) to measure metabolism in the basal ganglia and thalamus. Sixteen patients undergoing surgical evaluation were studied with 18F fluorodeoxyglucose (FDG) interictally and had intensive extracranial and intracranial electrophysiologic evaluations. Eight patients had left temporal lobe seizure foci, six had right temporal lobe foci, and two had right posterotemporal or parietal foci. The PET data were analyzed visually and quantitatively, using a multivariate analysis of variance on the quantitative data. Hypometabolism of subcortical nuclei was present ipsilateral to the cortical seizure focus. Cortical hypometabolism was noted focally in the temporal lobe in patients with left temporal lobe seizure foci, whereas patients with right temporal lobe seizure foci had diffuse hemispheric hypometabolism. We postulate that the subcortical hypometabolism is secondary to decreased efferent activity from temporal lobe structures, in particular amygdala and hippocampus, to subcortical nuclei. Diminished subcortical activity may then lead to defective regulation of cortical excitability in the temporal lobe, increasing the likelihood of seizure development and spread. PMID- 2108015 TI - Longitudinal clinicoelectrophysiologic study of a case of Lafora disease proven by skin biopsy. AB - A longitudinal clinicoelectrophysiologic study was undertaken of a 15-year 2 month-old girl with Lafora disease who was diagnosed by skin biopsy and an immunohistochemical method with antisera against Lafora bodies. From age 10 years 5 months, 4 months after onset, EEG disclosed progressive deterioration of background activity and incremental increase in epileptic discharges. Photosensitivity was unique: Occipital spikes and diffuse spike-wave discharges were provoked by low-frequency repetitive photic stimuli but without elicitation of myoclonic seizures. Photosensitivity completely disappeared after age 13 years 10 months. High-voltage somatosensory evoked potentials (SEPs) and high-voltage flash visual evoked potentials (F-VEPs) were seen before age 13. After age 13, progressive prolongation of I-III and I-V interpeak latencies of auditory brainstem responses (ABRs), progressive prolongation of latencies of photoevoked eyelid microvibrations, delayed latencies of pattern-reversal visual evoked potentials, and a decrease in the V/I amplitude ratio of ABRs and the previously high F-VEP amplitudes were observed. PMID- 2108016 TI - Edema associated with long-term valproate therapy. AB - Scattered reports of facial and limb edema have been reported, predominantly in the context of valproate (VPA)-induced hepatic injury. We report seven patients with edema associated with long-term VPA therapy in the absence of hepatic disease. PMID- 2108017 TI - Markedly increased omega-oxidation of valproate in fulminant hepatic failure. AB - Using gas chromatography-mass spectrometry, we showed that the urinary metabolite profile of valproate (VPA) in a subject receiving VPA and phenobarbital (PB) who died of fulminant hepatic failure was quite different from those of reported patients with Reye's syndrome or fatal hepatic failure. Only 2-n-propylglutarate, the end product of omega-oxidation of VPA, was excreted in markedly increased amounts, while other VPA metabolites were undetectable. Although the primary cause of fulminant hepatitis and the mechanism of enhanced VPA metabolism by the hepatic P-450 system in this patient are not clear, our findings suggest that P 450-mediated reactions become the predominant metabolic pathway of VPA in a stage of fulminant hepatic failure. PMID- 2108018 TI - High performance capillary electrophoresis of calmodulin. AB - The electrophoretic properties of purified calmodulin were investigated. High performance capillary electrophoresis of this Ca2+(-)binding protein in free solution at pH 2.5 resulted in an elution of a single peak with a retention time of approximately 4.7 min. Addition of [ethylene-bis(oxyethylenenitrilo]) N,N,N',N'-tetraacetic acid (EGTA) to the protein prior to capillary electrophoresis completely abolished this electrophoretic profile. Polyacrylamide gel electrophoresis of calmodulin under denaturing and nondenaturing conditions also revealed a single polypeptide band. However, the relative electrophoretic mobilities of this protein could vary, depending on the presence or absence of Ca2+. The pI of calmodulin was estimated to be 3.7 by using isoelectric focusing techniques. Analysis of this acidic protein by high performance capillary electrophoresis at pH 8.0 revealed that it could be resolved into two major and one minor polypeptide peaks, regardless of the presence or absence of Ca2+. These findings suggest that capillary electrophoresis at near physiological pH may differentiate the microheterogeneity of calmodulin. PMID- 2108019 TI - The interference of EDTA in searching for heat-stable low-Mr inhibitors of protein kinases. PMID- 2108020 TI - Identification of carboxylic acid residues in glucoamylase G2 from Aspergillus niger that participate in catalysis and substrate binding. AB - Functionally important carboxyl groups in glucoamylase G2 from Aspergillus niger were identified using a differential labelling approach which involved modification of the acarbose-inhibited enzyme with 1-ethyl-3-(4-azonia-4,4 dimethylpentyl)carbodiimide (EAC) and inactivation by [3H]EAC following removal of acarbose. Subsequent sequence localization of the substituted acidic residues was facilitated by specific phenylthiohydantoins. The acid cluster Asp176, Glu179 and Glu180 reacted exclusively with [3H]EAC, while Asp112, Asp153, Glu259 and Glu389 had incorporated both [3H]EAC and EAC. It is conceivable that one or two of the [3H]EAC-labelled side chains act in catalysis while the other fully protected residue(s) participates in substrate binding probably together with the partially protected ones. Twelve carboxyl groups that reacted with EAC in the enzyme-acarbose complex were also identified. Asp176, Glu179 and Glu180 are all invariant in fungal glucoamylases. Glu180 was tentatively identified as a catalytic group on the basis of sequence alignments to catalytic regions in isomaltase and alpha-amylase. The partially radiolabelled Asp112 corresponds in Taka-amylase A to Tyr75 situated in a substrate binding loop at a distance from the site of cleavage. A possible correlation between carbodiimide modification of an essential carboxyl group and its role in the glucoamylase catalysis is discussed. PMID- 2108021 TI - Arrangement of disulfide bridges and positions of sulfhydryl groups in tetanus toxin. AB - Tetanus toxin is a 151-kDa protein. The complete amino acid sequence is known. The mature toxin is made up of two peptide chains and contains 10 half-cystine residues. Treatment with 4-vinylpyridine in the presence of 6 M guanidine converted six of them into S-pyridylethyl cysteine residues as determined by amino acid analysis. When alkylation was preceded by mercaptolysis, all 10 half cystine residues were recovered in the S-pyridylethylated form. It was therefore concluded that the toxin contains six sulfhydryl groups and two disulfide bonds. The positions of the residues carrying sulfhydryl groups and of those involved in disulfide bridges were determined by labelling of the toxin alternatively with 4 vinylpyridine or with 4-dimethylaminoazobenzene-4'-iodoacetamide (DABIA), directly or after mercaptolysis. The toxin derivatives were cleaved with cyanogen bromide and the elution patterns in reversed-phase HPLC compared. The chromatography components were identified by N-terminal amino acid sequence and amino acid composition. In the chromatography of the non-mercaptolysed, DABIA treated sample four chromophore-carrying components were detected which could be demonstrated by N-terminal sequence analysis to correspond to six half-cystine containing cyanogen bromide fragments. In the mercaptolysed, DABIA-treated sample three additional chromophore-carrying components were present, corresponding to two previously disulfide-linked cyanogen bromide fragments and one fragment which had contained an internal disulfide bridge. The HPLC patterns showed characteristic differences as the DABIA-labelled fragments were considerably more hydrophobic than the corresponding vinylpyridine-labelled fragments. It was established that the half-cystine residues in positions 26, 185, 198, 311, 868, and 1300 are present in the sulfhydryl form, that those in positions 438 and 466 are disulfide-bridged, thereby connecting the light and heavy chains of the toxin, and that those in positions 1076 and 1092 are disulfide-bridged, thereby giving rise to a loop in the heavy chain. During the progress of the investigations about 20% of the amino acid sequence previously predicted from DNA analysis was confirmed by protein-chemical methods. PMID- 2108022 TI - Novel hyperglycosylated weak gelatin-binding fibronectin from human fetal placenta. Fractionation of a high poly(N-acetyllactosamine) fragment by tomato lectin affinity chromatography. AB - A novel hyperglycosylated fraction of human term fetal placental fibronectin was detected by long-term affinity binding to gelatin-Sepharose. An 18-h batch-wise gelatin-binding step was necessary to obtain a very low-affinity binding fraction, characterized by especially high N-acetylglucosamine and galactose content, and diffuse, poorly stained Coomassie bands on SDS/polyacrylamide electrophoretograms. The presence of a high proportion of long 7-10-kDa poly(N acetyllactosamine)-containing N-linked carbohydrate chains was confirmed by their gel permeation behavior, susceptibility to endo-beta-galactosidase and by methylation analysis. Our previous results suggest that 4.5-7-kDa poly(N acetyllactosamine) structures reduce the binding of fibronectin and its chymotryptic Ala260-Trp599 subdomain GB44 to gelatin [Zhu, B. C. R. & Laine, R. A. (1985) J. Biol. Chem. 260, 4041-4045]. Based on a gradient of urea used to dissociate gelatin-bound GB44, in the present study, fractions containing the novel 7-10-kDa carbohydrates showed significantly weaker binding to gelatin. Weak gelatin-binding characteristics of this novel hyperglycosylated fraction suggest that extended poly(N-acetyllactosamine) N-linked chains can significantly weaken heterotropic binding functions of fetal glycoproteins. The combined properties of weak Coomassie staining and weak gelatin binding have caused the novel hyperglycosylated fibronectin to be overlooked in previous investigations. PMID- 2108023 TI - Inhibition of UDP-glucuronosyltransferase activity by possible transition-state analogues in rat-liver microsomes. AB - A series of possible transition state analogues of the glucuronidation reaction catalyzed by UDP-glucuronosyltransferase were tested for their inhibitory effect on glucuronidation of various substrates in a rat liver microsomal fraction. In general 4-nitrophenol glucuronidation was more effectively inhibited than that of 1-naphthol, bilirubin or testosterone. 2-(1-Naphthyl)ethyl-UDP and 2,2,2 (triphenyl)ethyl-UDP were the most effective inhibitors. Their inhibitory effect was competitive towards both UDP-glucuronic acid and 4-nitrophenol. These compounds were much more effective inhibitors than UDP; therefore addition of a lipophilic group enhances the inhibitory potency of UDP. The various UDP derivatives showed differences in their abilities to inhibit the glucuronidation of the four acceptor substrates, supporting the concept that the different forms of UDP-glucuronosyl transferase have different active sites. PMID- 2108024 TI - Polychlorinated biphenyls increase fatty acid desaturation in the proliferating endoplasmic reticulum of pigeon and rat livers. AB - 1. Polychlorinated biphenyls (PCB) are abundant and persistent pollutants in the ecosystem. Commercial mixtures (e.g. Aroclor 1254) can contain up to 80 different isomers and congeners, many of which accumulate in biological systems by the ingestion of PCB-contaminated lipid components of food chains. 2. Commercial mixtures of PCB induce, in hepatic microsomal membranes in vivo, a variety of different forms of the cytochrome P-450 components of enzyme systems involved in the metabolism of drugs and other xenobiotics, and can also induce the proliferation of this membrane. Since these microsomal enzyme systems share a number of the requirements of microsomal fatty acid desaturases, we have investigated whether the induction by PCB in vivo of cytochrome-P-450-linked enzymes in the proliferating hepatic microsomal membrane of the pigeon and the rat is accompanied by increased proportions of polyunsaturated fatty acids in this membrane. 3. The most striking changes observed 120 h after treating pigeons and rats with 1.5 mmol Aroclor 1254/kg body mass were 2.2-fold and 1.6-fold increases, respectively, in the proportion of arachidonic acid in the hepatic microsomal membrane. When the effects of this treatment on the proliferation of this membrane and increase in liver mass are taken into account, the amount of arachidonic acid in the total microsomal membrane of pigeon and rat livers increased 6.7-fold and 1.9-fold, respectively. 4. These changes were accompanied by very significant increases in pigeons and rats of the concentration of hepatic microsomal cytochrome P-450, and in the activity in microsomal protein of a wide range of cytochrome P-450-dependent enzyme involved in the metabolism of drugs and other xenobiotics. 5. This effect of PCB, of increasing in vivo the degree of unsaturation of fatty acids of hepatic microsomal membrane, appears to be a novel finding, and does not seem to have been investigated for other drugs and xenobiotics. Preliminary results have shown that the effect is accompanied by substantial increases in the total activity of delta 6 and delta 5 microsomal fatty acid desaturases converting 18:2 (9, 12) (linoleic acid) to 20:4 (5, 8, 11, 14) (arachidonic acid) [Borlakoglu, J.T., Dils, R.R., Edwards-Webb, J.D. & Walker, C.H. (1988) Biochem. Soc. Trans. 16, 1072]. 6. It is postulated that there is a significant link between increased fatty acid desaturation and the induction of cytochrome-P-450-linked enzymes, and this is discussed in terms of the mechanisms involved in the metabolism of foreign compounds. PMID- 2108025 TI - Localization of phosphoserine residues in the alpha subunit of rabbit skeletal muscle phosphorylase kinase. AB - The alpha subunit of skeletal muscle phosphorylase kinase, as isolated, carries phosphate at the serine residues 1018, 1020 and 1023. Employing the S-ethyl cysteine method, these residues are found to be phosphorylated partially, i.e. differently phosphorylated species exist in muscle. Serine 1018 is a site which can be phosphorylated by the cyclic-AMP-dependent protein kinase. The serine residues 972, 985 and 1007 are phosphorylated by phosphorylase kinase itself when its activity is stimulated by micromolar concentrations of Ca2+. These phosphorylation sites are not identical to those found to be phosphorylated already in the enzyme as prepared from freshly excised muscle. A 'multiphosphorylation loop' uniquely present in this but not in the homologous beta subunit contains all the phosphoserine residues so far identified in the alpha subunit. PMID- 2108026 TI - Platelet protein phosphorylation and protein kinase C activation by phorbol esters with different biological activity and a novel synergistic response with Ca2+ ionophore. AB - Phorbol esters with different biological activities have been tested for their ability to induce the phosphorylation of human platelet proteins. We have shown that only the potent platelet aggregatory phorbol esters were able to stimulate the phosphorylation of proteins of 76, 68, 47, 30 and 20 kDa in intact platelets. The ability of these esters to stimulate phosphorylation of the 47-kDa protein ('p47') correlated with their ability to cause platelet aggregation. When a non platelet aggregatory deoxyphorbol (12-deoxyphorbol 13-phenylacetate 20-acetate) was combined with a subthreshold dose of the Ca2+ ionophore, A23187, a large increase in phosphorylation of p47 and a fourfold decrease in Ka was observed. This was in contrast to a barely detectable stimulation of phosphorylation at micromolar levels of this phorbol ester in the absence of the ionophore. This synergism was not evident for the potent platelet aggregatory derivatives. The Ka for DOPPA with a mixture of total platelet protein kinase C was 530 nM in the absence of calcium decreasing to 120 nM in the presence of calcium. In the presence of calcium, 12-deoxyphorbol 13-phenylacetate 20-acetate was shown to stimulate preferentially one of the isoforms of protein kinase C. PMID- 2108027 TI - NMR and molecular dynamics studies of the mKr2 'zinc finger'. AB - We determined the structure of a 30-amino-acid 'zinc finger' motif from the mouse Kruppel-like gene mKr2 in solution in the absence of metal ions by two dimensional NMR, distance geometry and restrained molecular dynamics methods. The most prominent secondary structural feature of the peptide is a helix extending from Ser14 to Ile20. The zinc-containing structure of the peptide was simulated by molecular dynamics calculations with restraints derived from the known geometry of the zinc ion and the ligating amino acid residues Cys6, Cys9, His22, His26. The latter structure does not deviate markedly from the set of structures determined for the zinc-free peptide, i.e. this peptide can accommodate a Zn2+ ion without major structural rearrangements. Thus, we propose that the metal ion stabilizes the existing three-dimensional peptide structural motif rather than introducing novel structural features. PMID- 2108028 TI - Frequent isolation of capnophilic bacteria in aspirate from Bartholin's gland abscesses and cysts. AB - Aspirate samples were obtained from 73 patients undergoing surgery for a Bartholin's gland abscess or cyst. Capnophilic bacteria were isolated from 22% of cases, in contrast to previous reports of sporadic isolation. The three Streptococcus pneumoniae isolates were serotype 3 or 4. The eight Haemophilus influenzae isolates could not be serotyped; six of them were biotype II but the electrophoretic band patterns of their outer membrane proteins were heterogeneous, indicating that non-serotypable strains from the same anatomical site may not be related. Four Neisseria gonorrhoeae isolates and one strain of Neisseria subflava were recovered. The role of capnophilic bacteria in the pathogenesis of infections of the Bartholin's gland remains to be clarified. PMID- 2108029 TI - The enterococci: an enigma and a continuing therapeutic challenge. PMID- 2108031 TI - CAST and beyond. Implications of the cardiac arrhythmia suppression trials. By the Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. PMID- 2108030 TI - Recent taxonomic changes in the genus Enterococcus. AB - Recent taxonomic changes among the catalase-negative gram-positive cocci have led to the recognition of a separate genus for bacteria previously considered to be members of the genus Streptococcus. Presently, a total of 12 species of the genus Enterococcus have been described. The characteristics, taxonomy and nomenclature of these species, along with the possible clinical implications of revised enterococcal taxonomy, are discussed. PMID- 2108032 TI - Experimental atherosclerosis: effects of oestrogen and atherosclerosis on thromboxane and prostacyclin formation. AB - We evaluated the effect of oestrogen and experimental atherosclerosis on the in vivo formation of thromboxane and prostacyclin in rabbits. Twenty-four New Zealand White rabbits were divided into four groups. One group received control diet, one group received control diet and oestrogen, one group received control diet supplemented with 1% cholesterol and one group received cholesterol supplemented diet and oestrogen during 3 months. The in vivo formation of thromboxane and prostacyclin were measured as 2,3-dinor-TxB2 and 2,3-dinor-6-keto PGF1 alpha in urine by gas chromatography/mass spectrometry. All rabbits on cholesterol diet became hypercholesterolaemic and developed atherosclerosis. As in previous experiments cholesterol and oestrogen-treated rabbits had only minor atherosclerosis compared to purely cholesterol-fed rabbits. The in vivo production of thromboxane in oestrogen-treated rabbits decreased from 1641 +/- 162 pg mg-1 creatinine pretreatment to 808 +/- 92 pg mg-1 creatine at 12 weeks (P = 0.0001). In contrast, the in vivo production of prostacyclin increased during oestrogen treatment (P = 0.0027). The in vivo production of prostacyclin decreased during pure cholesterol feeding without oestrogen 1384 +/- 219 pg mg-1 creatinine to 702 +/- 142 pg mg-1 creatinine (P = 0.0091). The ratio of in vivo prostacyclin to thromboxane formation increased 2-3-fold during oestrogen therapy (P = 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108033 TI - Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance. AB - Renal tubular sodium handling was evaluated in 27 non-azotemic cirrhotic patients with ascites and positive sodium balance and in 17 controls after at least 5 days of a constant sodium intake using the lithium clearance as an index of fluid delivery to the distal tubule. Plasma renin activity and plasma aldosterone were also evaluated. Sodium fractional excretion, filtered sodium load, absolute sodium distal delivery, lithium fractional excretion and absolute distal sodium reabsorption were significantly lower in cirrhotics than in controls (0.58 +/- 0.11 vs. 1.29 +/- 0.12%, P less than 0.001; 12529 +/- 677 vs. 15707 +/- 796 microEq min-1 1.73 m-2 BSA, P less than 0.005; 2384 +/- 135.2 vs. 3685 +/- 219.3 microEq min-1 1.73 m-2 BSA, P less than 0.001; 19.5 +/- 1.0 vs. 24.2 +/- 1.3%, P less than 0.01; 2299 +/- 127 vs. 3485 +/- 214 microEq min-1 1.73 m-2 BSA, P less than 0.001, respectively). A correlation was found between lithium clearance and sodium clearance only in cirrhotic patients (r = 0.62; P less than 0.01). Distal sodium reabsorption evaluated as a per cent of filtered sodium load was lower in cirrhotics than in controls (19.1 +/- 1.0 vs. 22.4 +/- 1.2%, P less than 0.05) while distal sodium reabsorption evaluated as a per cent of sodium distal delivery was higher in cirrhotics than in controls (96.7 +/- 0.4 vs. 94.4 +/- 0.5%, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108034 TI - Increased hepatic efficacy of urea synthesis from alanine in insulin-dependent diabetes mellitus. AB - The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and in 18 patients with insulin-dependent diabetes mellitus (HbAlc = 8.4 +/- 1.0% (mean +/- SD)). Following an overnight fast alanine was infused at 2 mmol h-1 kg-1 body weight. The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water and intestinal hydrolysis. The functional hepatic nitrogen clearance, i.e. the relation of urea synthesis rate to blood alanine concentration, was calculated as the slope of linear regression of urea synthesis rates on blood alanine concentrations. Fasting glucagon concentrations were 85 +/- 26 ng l-1 in controls and 161 +/- 35 ng l-1 (P less than 0.01) in patients. The functional hepatic nitrogen clearances were 21.8 +/- 4.4 l h-1 in controls and 44.7 +/- 12.4 l h-1 (P less than 0.001) in patients. By multiple step-wise linear regression analysis the functional hepatic nitrogen clearance was found to correlate independently to fasting glucagon concentration, duration of diabetes, change in blood glucose and insulin following alanine infusion (r2 = 0.74). In a simple linear regression analysis the functional hepatic nitrogen clearance correlated strongly to fasting glucagon concentration (r2 = 0.54). In conclusion the kinetics of urea synthesis in insulin-dependent diabetes is changed in favour of increased conversion of alanine-N to urea-N at any blood amino acid concentration. The increased FHNC correlates strongly with hyperglucagonaemia. PMID- 2108035 TI - Normalization of enhanced hepatic gluconeogenesis by the antiglucocorticoid RU 38486 in acutely uraemic rats. AB - Hepatic amino acid uptake, urea and glucose production are increased in acute uraemia. It has been shown that this metabolic pattern is mediated by glucocorticoids. Accordingly, the administration of the antiglucocorticoid RU 38486 to acutely uraemic rats resulted in a reduction of serum urea-N and glucose levels. To clarify whether this effect is due to a reduction in hepatic gluconeogenesis we examined the effect of the antiglucocorticoid RU 38486 on urea and glucose formation in isolated hepatocytes from sham-operated (SHAM) and bilaterally nephrectomized (BNX) rats receiving RU 38486 or the vehicle only. Hepatic glucose production in BNX rats was considerably increased from Na pyruvate (+79%), alanine (+174%), glutamine (+158%), and serine (+87%) compared with SHAM animals. Concomitantly, hepatic urea formation was also enhanced from amino acid substrates in acutely uraemic rats. When uraemic animals were treated with RU 38486, glucose production from amino acids and Na-pyruvate was reduced to the range of SHAM animals or even lower. This effect could not be demonstrated in SHAM-operated controls. A comparable decrement in hepatic urea production was observed in BNX rats treated with the antiglucocorticoid. Thus, glucocorticoids appear to play a key role in the abnormal hepatic urea and glucose production of acutely uraemic rats. PMID- 2108036 TI - The effect of amino acid infusion on leg protein turnover assessed by L [15N]phenylalanine and L-[1-13C]leucine exchange. AB - A stable isotope technique depending on the use of [15N]phenylalanine and [1 13C]leucine to assess exchange was utilized to measure the components of protein turnover of the human leg and the effects of amino acid infusion. Eight healthy subjects (28.5 +/- 2.5 years) were studied when post-absorptive in the basal state and again during infusion of a mixed amino acid solution (55 g l-1, 1.52 ml kg-1 h-1). During the basal period leucine oxidation by the leg was 4.4 +/- 2.0 nmol 100 g-1 min-1 and this increased threefold during amino acid infusion (13.6 +/- 3.1 nmol 100 g-1 min-1, mean +/- SEM, P = 0.003). Amino acid infusion abolished the net negative balance between incorporation of leucine into, and release from, protein (basal, -31.8 +/- 5.8; during infusion, +3.1 +/- 7.1 nmol 100 g-1 P = 0.001). Phenylalanine exchange showed a similar pattern (basal, -13.7 +/- 1.8; during infusion, -0.8 +/- 3.0 nmol 100 g-1 min-1, P = 0.003). Basal entry of leucine into leg protein (i.e. protein synthesis) was 70.0 +/- 10.8 nmol 100 g-1 min-1 and this increased during amino acid infusion to 87.3 +/- 14.1 nmol 100 g-1 min-1 (P = 0.11). Phenylalanine entry to protein also increased with amino acid infusion (29.1 +/- 4.5 vs. 38.3 +/- 5.8 nmol 100 g-1 min-1, P = 0.09). Release from protein of leucine (101.8 +/- 9.1 vs. 84.2 +/- 9.1 nmol 100 g-1 min 1, P = 0.21) and of phenylalanine (42.8 +/- 4.2 vs. 39.1 +/- 4.2 nmol 100 g-1 min 1, P = 0.50) was unchanged by amino acid infusion. The results suggest that, in the post-absorptive state in man, infusion of mixed amino acids, without additional energy substrates; reverses negative amino acid balance by a mechanism which includes stimulation of muscle protein synthesis but which does not alter protein breakdown. Interpretation of the results obtained concurrently on whole body protein turnover suggests that the increase in muscle protein synthesis contributes substantially to the whole-body increase, but the fall in whole-body breakdown with exogenous amino acids is independent of changes in muscle. PMID- 2108037 TI - Postpartum thyroid dysfunction and HLA status. AB - Nine-hundred-and-one women presenting in an antenatal clinic at the 60th week of pregnancy were tested for antithyroid antibodies. A group of 113 antibody positive women and 108 antibody-negative age-matched controls were HLA typed and followed prospectively at 6-weekly intervals through pregnancy and for 12 months postpartum. Forty-five of the women developed biochemical evidence of postpartum thyroid dysfunction (PPTD) of whom 36 were antibody positive. Compared with a local control population (n = 600), and using multiplex analysis, there was a significant increase in the combinations HLA B8, DR3 and HLA A1, B8, DR3 from 22.5% to 40.0% (P less than 0.02) and from 18.6% to 35.6% (P less than 0.01) respectively in the women who developed PPTD. The well-recognized association of these haplotypes with other organ-specific autoimmune diseases provides further support for autoimmune events being implicated in the development of PPTD. PMID- 2108038 TI - Autoradiographic localization of Na(+)-dependent L-valine uptake by the jejunum of streptozotocin-diabetic rats. AB - The mechanisms involved in the increased Na(+)-dependent nutrient uptake across intestine of diabetic animals are poorly understood. Here we have studied the effect of acute (7d) and chronic (30-40d) diabetes on the autoradiographic localization of 3H-L-valine accumulation by rat jejunal villi and on enterocyte migration rate. In control rats, Na(+)-dependent valine uptake was confined to enterocytes on the upper 20-23% of the villus. In intestine from diabetic rats, however, this area was extended to occupy the upper 42-45% of an enlarged villus surface. Hyperphagia was not responsible for the expanded functional surface and systemic factors are therefore implicated in the adaptive response. Enterocyte migration rate was found to be unaffected by diabetes but an increased villus height in this condition resulted in an additional 13.5 h in enterocyte lifespan. These data are compatible with the hypothesis that during diabetes the earlier maturation of enterocyte absorptive function produces an epithelial surface containing a higher proportion of mature enterocytes. PMID- 2108039 TI - Altered collagen metabolism in osteogenesis imperfecta fibroblasts: a study on 33 patients with diverse forms. AB - The pattern of collagen metabolism was analysed in fibroblast cultures from patients with diverse forms of osteogenesis imperfecta (OI). Generally, OI fibroblasts show an insufficient collagen synthesis which is most obvious in patients between 2 and 9 years of age during which period control fibroblasts have an elevated collagen synthesis. OI fibroblasts remain on a basal level except for fibroblasts from OI type IV patients which seem to approach normal levels. In addition, OI fibroblasts generally show a slightly increased degradation of newly synthesized collagen which again is most obvious between 2 and 9 years. These differences in collagen degradation, however, only contribute to a minor extent to the lack of net collagen synthesis during early childhood. No correlation could be found between the degree of overmodification of collagen and its degradation since fibroblasts of both OI type I and OI type II have an elevated degradation though only the latter ones produce overmodified collagen molecules. Pulse labelling of collagen with radioactivity labelled sugars was used to distinguish between normal collagen chains or CNBr-derived peptides and those which were overmodified. In all three cases studied (OI II, OI III, OI IV) the entire triple helical domain of alpha 1(I) and alpha 2(I) was overglycosylated. The amount of overmodification, however, was not uniform but rather unique for each patient studied. We assume that the molecular defects in the majority of OI cases may be located in the mechanisms operating on the control of both the age appropriate synthesis of collagen and its degree of post translational modification. PMID- 2108040 TI - Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres. AB - In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY LI), vasoactive intestinal peptide-LI (VIP-LI), substance P-LI (SP-LI) and calcitonin generated peptide-LI (CGRP-LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY-LI and SP-LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY-LI and SP-LI were significantly increased. CGRP-LI was not altered, despite the fact that this peptide co-exists in many tissues with SP. There was no change in VIP-LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho-adrenal system. PMID- 2108041 TI - The role of lipids in the pathogenesis of glomerulosclerosis in the rat following subtotal nephrectomy. AB - Similarities between atherosclerosis and glomerulosclerosis suggest that hyperlipidaemia may contribute to glomerular injury. Dietary supplementation with 4% cholesterol + 1% cholic acid was administered to rats 4 weeks after 1 1/3 nephrectomy and continued for 7 weeks. There was a significant increase in serum cholesterol (peak = 11.52 +/- 1.09 mmol l-1 vs. 4.73 +/- 0.31 on control diet, P less than 0.001) and triglyceride concentrations (peak = 2.31 +/- 0.27 mmol l-1 vs. 1.41 +/- 0.29, P less than 0.05) and a marked increase in beta-migrating lipoproteins. The severity of hypercholesterolaemia was significantly correlated with proteinuria (control diet: r = 0.600, cholesterol diet: r = 0.672, P less than 0.0001) as was hypertriglyceridaemia (control diet: r = 0.544, cholesterol diet: r = 0.678, P less than 0.0001). The percentage of glomeruli containing lipid deposits was increased from 21% to 60% (P less than 0.05). The kidney total cholesterol content was increased from 29.2 +/- 0.8 to 47.7 +/- 3.3 mumols g-1 dry weight (P less than 0.0001), with esterified cholesterol increasing from 7.5 +/- 0.4% to 14.5 +/- 2.1% of total (P less than 0.01). Serum cholesterol concentration was significantly correlated with both glomerular lipid deposition (rs = 0.7195, P less than 0.0001) and tissue total cholesterol content (rs = 0.6053, P less than 0.001). Lipid vacuolation was prominent in the paramesangium and within mesangial cells. Despite these changes hypertension, uraemia, proteinuria and glomerulosclerosis were not significantly increased on the cholesterol diet. Cholesterol deposition in the glomeruli occurs secondary to hyperlipidaemia in rats following subtotal nephrectomy but over 7 weeks no exacerbation of glomerulosclerosis is detectable. PMID- 2108042 TI - Murine thymocytes possess specific cell surface-associated exoaminopeptidase activities: preferential expression by immature CD4-CD8- subpopulation. AB - Murine thymocytes are shown to possess at least three well-defined exo-N aminopeptidase activities on their surface. One of them cleaves the prolyl bond in the synthetic dipeptide nitroanilide Gly-Pro-pNA (Km 0.95 mM and Vmax 8 nmol/h at pH 7.4 and 37 degrees C) and is specifically inhibited by phenylmethane sulfonyl fluoride, diprotin A, Gly-Pro-Ala and Gly-Pro-Gly-Gly. These data further support identification of this enzyme with a serine exopeptidase dipeptidyl peptidase IV (DPP IV), previously reported to be specific for collagen. The two other forms of N-exopeptidase activities are detected when Ala pNA and Leu-pNA are used as substrates. Leu-aminopeptidase activity (Km 1.4 mM, Vmax 15 nmol/h) and Ala-aminopeptidase activity (Km 4.0 mM, Vmax 20 nmol/h) are inhibited by inhibitors for thiol- and trypsin-like proteinases, i.e. tosyl lysyl chloromethyl ketone, leupeptin and N-ethylmaleimide. Addition inhibition of Leu aminopeptidase activity by peptstatin, a known inhibitor of carboxyl proteases, suggests that aminopeptidase activity detected with Leu-pNA is different in part from Ala-aminopeptidase activity. Among the various lymphoid cell populations tested, the three aminopeptidase activities are increased by three- to fourfold in the immature CD4-CD8- thymocyte subset as well as in the thymoma BW5147. In contrast, cortisone-resistant thymocytes, lymph node and spleen cells exhibit levels of activities almost similar to that of unfractionated thymocytes. During ontogeny, the levels of these activities are increased four- to sevenfold on fetal thymocytes (from days 14 to 16). Finally, when thymocytes or spleen cells are cultured with a mitogenic concentration of concanavalin A, their proliferative responses are correlated with an enhancement of the aminopeptidase activities (1.3- to 5-fold). From these results, a correlation between the presence of these peptidases on the cell surface of immature and mature lymphoid cells and biological responsiveness is suggested. PMID- 2108043 TI - Sequential appearance of gamma/delta- and alpha/beta-bearing T cells in the peritoneal cavity during an i.p. infection with Listeria monocytogenes. AB - To search for a potential role of T cell antigen receptor (TcR) gamma/delta bearing cells in host-defense against Listeria monocytogenes, we analyzed the sequential appearance of gamma/delta and alpha/beta T cell in the peritoneal exudate cells (PEC) during an i.p. infection with sublethal dose (2 X 10(3) of viable Listeria organisms in mice. The PEC on day 1 after the infection consisted of 48% macrophages and 50% lymphocytes, most of which were surface IgM+ (B) cells. The number of PEC increased to the maximal level by day 3. The PEC at this stage contained an appreciable number of CD3+ T cells in addition to a large number of macrophages. Of the CD3+ cells, the proportion of CD4- CD8- cells, most of which expressed no TcR alpha/beta, increased to the maximal level on day 3 after the infection. In correlation with an increased number of CD3+ CD4- CD8- TcR alpha/beta- cells, high level of TcR gamma/delta chain gene messages was detected in the nonadherent population of the PEC on this stage. On the other hand, the PEC on day 8 contained an increased number of CD4+ CD8- and CD4- CD8+ cells which expressed TcR alpha/beta chain on their surface. These results suggest that the gamma/delta T cells precede the alpha/beta T cells in appearance during listerial infection. The gamma/delta T cells may be involved at the first line of the host-defense against Listeria. PMID- 2108044 TI - In rat B lymphocyte genesis sixty percent is lost from the bone marrow at the transition of nondividing pre-B cell to sIgM+ B lymphocyte, the stage of Ig light chain gene expression. AB - The cycling B precursor cells in rat bone marrow (BM) that carry the B220 antigen and no surface Ig daily produce 780 million new cells. The pool of recirculating B lymphocytes in the rat, however, renew at a rate of only about 40 million cells/day. To analyze at which stages in B lymphocyte genesis the cell loss occurs, we identified post-mitotic cells in the rat BM B lineage, and determined their renewal rates. We used 5-bromo-deoxyuridine (BrdUrd) to label DNA synthesizing cells, identifying incorporated BrdUrd with the mouse monoclonal antibody BU-1. B lineage cell subsets were identified by the markers HIS24 antigen (rat B220), terminal deoxynucleotidyl transferase (TdT), Ig mu heavy chain, and complete Ig. By use of double and triple immunocytology, we determined the extent of BrdUrd incorporation in the various B lineage compartments [HIS24+TdT-Ig-, TdT+, cytoplasmic mu chain (c mu)+ surface (s) IgM- pre-B, sIgM+ B]. Both sIgM+ B lymphocytes and all B precursors with cell diameters less than 11-12 microns were virtually devoid of DNA synthesis, as indicated by S-phase indices below 2%. In contrast, S-phase indices of large B precursors ranged between 43%-66%. We established the renewal rates of nondividing BM B lineage cells by placing osmotic minipumps containing BrdUrd subcutaneously in the flank of rats. The nondividing BM B lineage cells all renewed rapidly at rates between 2.4% and 5.6%/h, representing average half-lives of 29 to 12 h. In absolute numbers, the renewal/day/whole body BM was 165 X 10(6) for sIgM+ B lymphocytes, 422 X 10(6) for small c mu+ sIgM- pre-B cells, 89 X 10(6) for small TdT+ cells and 35 X 10(6) for small HIS24+TdT-Ig- cells. Assuming that recirculating B lymphocytes in the periphery are the descendants of BM sIgM+ B lymphocytes, which in their turn are the progeny of small pre-B cells, the renewal data indicate the following. Of the 165 million potentially available BM B lymphocytes, only 40 million cells become incorporated in the pool of recirculating B lymphocytes, representing a loss of 75%. BM B lymphocytes, in turn, use only (165/422 X 100% = ) 40% of the potential output from their immediate precursors. The 60% loss that occurs here may reflect the extent of aberrant Ig light chain gene rearrangement in normal B lymphocyte genesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2108045 TI - Differences in specificity of "DPw2-specific" cytotoxic T cell clones revealed with HLA-mutant lines: evidence that non-DP HLA genes influence recognition by some clones. AB - Seven allospecific cytotoxic T lymphocyte (CTL) clones derived from DPw2-specific bulk populations were characterized by three approaches to obtain a more detailed understanding of the T cell recognition of the HLA-DPw2 molecule. All seven of the clones were DPw2 specific and indistinguishable in specificity by three approaches: (a) patterns of lysis of panels of targets from normal donors; (b) inhibition of lysis by anti-class II monoclonal antibodies (mAb); (c) lysis of mutant lymphoblastoid B cell lines (LCL) with isolated loss of DP2 alpha or DP2 beta gene expression (as a result of selection for resistance to DPw2-specific CTL). However, only four of the seven CTL clones (which we designate "orthodox") lysed all mutant DPw2+ LCL tested; the other three ("heterodox") CTL clones showed reduced or no lysis of particular LCL which expressed DPw2 but had been mutagenized and selected for loss of DR expression. Cold target blocking experiments with the mutant LCL confirmed differences in: (a) specificity among CTL clones and (b) CTL-defined phenotype among serologically indistinguishable DR DPw2+ mutant LCL. Differences were not explained by different levels of DP expression by the mutant LCL. Given the nature of the mutagens and mutations, it is highly improbable that point mutations in DP account for differences in recognition. These data suggest that non-DP HLA genes influence recognition by some DP-specific clones, potentially due to corecognition of HLA-DR alpha or another non-DP HLA product in the context of a DPw2 alpha/beta dimer. PMID- 2108046 TI - Lymphokines and bacteria, that induce tumoricidal activity, trigger a different secretory response in macrophages. AB - The abilities of various macrophage-activating agents to trigger tumoricidal activity and/or the secretion of prostaglandin E2 (PGE2), interleukin 6 (IL 6) and transforming growth factor beta (TGF beta) in bone marrow-derived mononuclear phagocytes (BMM phi) in vitro were comparatively assessed. Induction of tumoricidal activity by lymphokines, that is only short-lived, was not associated with enhanced secretion of these activities by BMM phi; in contrast, incubation with heat-killed facultative intracellular bacteria resulted in persisting tumoricidal activity and in marked enhancement of the secretion of IL 6 and PGE2, but not of TGF beta activity. These findings support the concept that the pattern of the secretory response induced in macrophages by lymphokines differs from that triggered by bacteria and that the rapid decay of lymphokine-induced tumoricidal activity is not due to autocrine macrophage deactivation mediated by one of these agents alone. PMID- 2108047 TI - Density-dependent tumor cell death and reversible cell cycle arrest: mutually exclusive modes of monocyte-mediated growth control. AB - The population development of five human tumor cell lines is examined under the influence of elutriator-prepared human monocytes in a serum-free hormone- and growth factor-supplemented medium. Analysis was performed by electronic counting and sizing of tumor cell nuclei and flow cytometric detection of cell cycle phases. Tumor cell death is triggered at rather low monocyte:tumor cell ratios (1:2 to 1:4) whereas it is strongly reduced at high monocyte densities. Furthermore, it is shown that confluence of the target cell population is a necessary prerequisite for lysis. The data suggest that in monocyte/tumor cell cocultures the decision on target cell lysis is not made by the effector cell, but rather by the target cell and that the criterion for this decision is the target cell's ability or inability to respond to a monocyte challenge by arresting the cell cycle in G1. Interactions between target cells play an important role in determining the result of this decision process. A common basis is suggested for this kind of density-dependent monocyte-triggered lysis and density-dependent cell death in 3T3 cell cultures as described previously. PMID- 2108048 TI - Extracellular matrix of cultured glial cells: selective expression of chondroitin 4-sulfate by type-2 astrocytes and their progenitors. AB - We have studied the extracellular matrix composition of cultured glial cells by immunocytochemistry with different monoclonal and polyclonal antibodies. Double immunofluorescence experiments and metabolic labeling with [3H]glucosamine performed in different types of cerebellar and cortical cultures showed that bipotential progenitors for type-2 astrocytes and for oligodendrocytes (recognized by the monoclonal antibody LB1 at early stages of their development) synthesize chondroitin sulfate (CS) and deposit this proteoglycan in their extracellular matrix. The distribution of the various [3H]glucosamine-labeled glycosaminoglycans between the intracellular and the extracellular space was different. CS was present both within the cells and in the culture medium, although in different amounts. Bi-potential progenitors became also O4-positive during their development in vitro. At the stage of O4-positivity they were still stained with antibodies against CS. However, when the progenitor cells were maintained in serum-free medium and differentiated into Gal-C-positive oligodendrocytes, they became CS-negative. In the presence of fetal calf serum in the culture medium, the bipotential progenitors differentiated into GFAP-positive type-2 astrocytes. These cells still expressed CS: their Golgi area and their surface were stained with anti-CS antibodies. Staining with monoclonal antibodies specific for different types of CS (4-sulfate, 6-sulfate, and unsulfated) revealed that both bipotential progenitors and type-2 astrocytes synthesized only chondroitin 4-sulfate. Type-1 astrocytes were negative for both the polyclonal and the monoclonal anti-CS antibodies. Finally, type-2 astrocytes and their progenitors were weakly stained with anti-laminin antibodies and unstained with anti-fibronectin. Type-1 astrocytes were positive for both anti-laminin and anti fibronectin antibodies and appeared to secrete fibronectin in the extracellular space. PMID- 2108049 TI - Regulation of nuclear scaffold protease activity by calcium. AB - Recent investigations have disclosed protease activity which is intimately associated with the nuclear scaffold. This protease activity shows a marked selectivity for lamins A/C, and from them may produce the 46-kDa NTPase thought to participate in nucleocytoplasmic RNA transport. Preliminary characterizations suggested that the protease activity might require Ca2+. In this report, we present evidence showing that nuclear scaffold protease activity is stringently regulated by Ca2+ within the physiologic range. Further, calmodulin antagonists such as calmidazolium and chlorpromazine produce marked inhibition of the protease activity, suggesting modulation by calmodulin or calmodulin-like factors. PMID- 2108050 TI - Increases in collagen type IV and laminin in galactose-induced retinal capillary basement membrane thickening--prevention by an aldose reductase inhibitor. AB - Biochemical alterations in the composition of retinal capillary basement membrane components were investigated in galactosemic rats, an animal model that develops basement membrane lesions comparable to those of diabetic retinopathy. Normotensive Wistar-Kyoto rats fed a 30% galactose diet for 9 months developed significant thickening of retinal capillary basement membranes by comparison with animals fed a control test diet (P less than 0.001), or animals on a diet containing 30% galactose and 250 mg kg-1 of the aldose reductase inhibitor sorbinil (P less than 0.001). A quantitative electron microscopic immunogold technique applied on ultrathin sections of the retinas of these animals showed that the labeling densities of collagen type IV and laminin per unit cross sectional area (which is presumably proportional to the concentrations of these molecules) were significantly increased in the retinal capillary basement membranes of galactose-fed rats, compared with animals on the control test diet. Increases in these two components of basement membranes were prevented by addition of sorbinil to the diet. However, there was no significant change in the labeling density of heparan sulfate proteoglycan (HSPG) core protein in the basement membranes of galactose-fed rats in comparison to animals on either the control diet or galactose-sorbinil diet. Two types of striated fibrillar materials were frequently found in areas of focal thickening of basement membranes of galactose fed rats only. Thinner fibrils reacted strongly with collagen type III antibody, whereas thicker fibrils reacted weakly with collagen type I antibody. Our results indicate that there is an increase in labeling densities of collagen type IV and laminin in thickened basement membranes of retinal capillaries of galactosemic rats along with the expression of interstitial collagens like collagen type III and an abnormal collagen that weakly cross-reacts with antibody to collagen type I, and these effects of galactosemia on the basement membranes are preventable by an aldose reductase inhibitor. PMID- 2108051 TI - A 43 kDa form of the GTP-binding protein Gi3 in human erythrocytes. AB - Purified preparations of human erythrocyte G-proteins contain a 43 kDa pertussis toxin substrate which appears to be the alpha-subunit of a heterotrimeric GTP binding protein. The 43 kDa protein is recognized by antisera that are sequence specific for peptides encoding a sequence common to all 39-53 kDa G-protein alpha subunits. G alpha o-specific antiserum did not recognize 43 or 40-41 kDa alpha subunits. AS/6, which recognizes the alpha i proteins, recognized 43 kDa as well as 40-41 kDa proteins. Of the three antisera specific for individual members of the alpha i family, only the Gi3-specific antiserum recognized the 43 kDa erythrocyte G-protein. However, 40-41 kDa forms of all three alpha is are present. These observations indicate that human erythrocytes contain a novel 43 kDa form of Gi3. PMID- 2108052 TI - Conformational effects of nucleotide exchange in ras p21 proteins as studied by fluorescence spectroscopy. AB - The intrinsic fluorescence properties of the oncogene protein p21N-ras,p21H-ras and one of its transforming mutants, p21N-ras (Val12), have been investigated. A mutant containing a single tryptophan at position 28 in p21H-ras (Trp28) has been specifically engineered to provide a probe of protein conformation on nucleotide binding. The proteins produced essentially similar circular dichroism spectra typical of alpha/beta proteins. A decrease in the intensity of the fluorescence emission spectrum due to tyrosine occurred on GDP/GTP nucleotide exchange in the native and mutant proteins. Selective excitation of the single tryptophan in p21 produced a decrease in fluorescence intensity which was accompanied by a blue shift in the wavelength of maximum emission on nucleotide exchange. A reduction in the residual Mg2+ ion concentration enhanced this effect. PMID- 2108053 TI - Effect of polyelectrolytes on serine proteinase secretion by Bacillus subtilis. AB - Addition of polycations with molecular masses of 5-40 kDa as well as Na+, stimulated serine proteinase secretion by Bacillus subtilis cells. Polyanions and higher-molecular-mass polycations (100-200 kDa) were inefficient. The enzyme yields in the presence of polycations or Na+ were equal in magnitude. The results indicate that the cations, apparently counteracting the negative surface charge of the bacterial plasma membrane, cause the desorption of the serine (alkaline) proteinase. The synthesis of the proteinase is inferred to be stopped as the enzyme is bound to the outer surface of the plasma membrane. The desorption of the enzyme thus induces the synthesis of the new portions of proteinase. PMID- 2108054 TI - Nucleotide sequence of the second psbG gene in Synechocystis 6803. Possible implications for psbG function as a NAD(P)H dehydrogenase subunit gene. AB - Nucleotide sequencing of the second Synechocystis 6803 psbG gene, psbG2 shows the predicted polypeptide to be 219 amino acids long. It is less similar to chloroplast psbG genes than is the Synechocystis psbG1 copy. Alignment with seven other psbG protein sequences, including that from the Paramecium mitochondrial genome reveals a central highly conserved region common to each. This is discussed as evidence supporting the proposal that the psbG polypeptide is a NAD(P)H dehydrogenase (complex I) subunit in cyanobacteria, chloroplasts and mitochondria. PMID- 2108055 TI - Two novel brain proteins, CaBP33 and CaBP37, are calcium-dependent phospholipid- and membrane-binding proteins. AB - Two acidic Ca2(+)-binding proteins (CaBP33 and CaBP37) purified from bovine brain have been characterized in terms of immunological properties, heat-sensitivity, electrophoretic mobility, and Ca2(+)-dependent binding to negatively charged phospholipids and to brain membranes. They were induced to bind to membranes by homogenization of brain tissue in the presence of CaCl2. The membrane-bound CaBP33/CaBP37 mixture resisted extraction with detergents and was solubilized with high concentrations of EGTA/KCl. However, apparent Ca2(+)-independent binding of the two proteins to membranes seemed to occur as well. This latter fraction of membrane-bound CaBP33 and CaBP37 could be solubilized with Triton X 100, indicating that brain membranes normally contain the two proteins as intrinsic components. PMID- 2108056 TI - The effects of combining norethindrone with a gonadotropin-releasing hormone agonist in the treatment of symptomatic endometriosis. AB - Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRH-a) is associated with side effects secondary to the induced hypoestrogenic state. In an effort to ameliorate these symptoms, 10 patients with symptomatic endometriosis self-administered the GnRH-a [D-His6(Imbzl)-Pro9-NET]-GnRH in combination with norethindrone daily for 24 weeks. Painful symptoms were significantly suppressed after therapy (P less than 0.005). Objective review of photographs taken at laparoscopy before and after therapy demonstrated significant reduction of visible implants (P less than 0.005). Vasomotor symptoms were minimized when compared with a group of 16 patients previously treated with GnRH-a alone. Bone mineral density of the distal radius assessed by single photon absorptiometry was not reduced during therapy, although lumbar spine bone density assessed by quantitative computerized tomography was minimally but reversibly reduced. No metabolic derangements were detected. The combination of norethindrone with GnRH-a is a well tolerated and effective means of treating symptomatic endometriosis. PMID- 2108057 TI - Leuprolide acetate lowers circulating bioactive luteinizing hormone and testosterone concentrations during ovarian stimulation for oocyte retrieval. AB - Levels of immunoreactive luteinizing hormone (LH), bioactive LH, and testosterone (T) were determined in 52 women receiving human menopausal gonadotropins (hMG). In 26 women receiving leuprolide acetate (LA) preceding hMG, there was a significant suppression of immunoreactive LH and bioactive LH. The characteristic increase in serum levels of bioactive LH and T were absent. Follicular fluid estradiol and T concentrations, and serum progesterone were not different. The lower circulating levels of T may reflect reduced LH-stimulated androgen accumulation in smaller nonaspirated follicles and may account for the enhanced follicle recruitment observed during LA. The lack of premature luteinization despite marked rises of bioactive LH in the absence of LA is consistent with normal events during the menstrual cycle and was due to the early termination of hMG stimulation. PMID- 2108058 TI - Transient hyperprolactinemia during cycle stimulation and its influence on oocyte retrieval and fertilization rates. AB - Prolactin (PRL) has been shown to have inhibitory effect on follicle-stimulating hormone induced aromatase activity and estrogen biosynthesis in human granulosa cells cultured in vitro. To investigate the validity of the hypothesis that transient hyperprolactinemia during controlled ovarian hyperstimulation might influence follicular steroidogenesis and oocyte maturation, we measured serum PRL, estradiol, and progesterone before aspiration of oocytes in women undergoing ovarian stimulation (n = 108) in in vitro fertilization-embryo transfer. No correlation was detected between PRL and total number oocytes, number mature oocytes, fertilization rate, cleavage rate, and pregnancy rate. Transient elevation of PRL was a common finding in patients (57%) but was not associated with a poor clinical outcome. PMID- 2108059 TI - Sperm counts and reproductive hormones in male marathoners and lean controls. AB - In women, chronic and intense endurance exercise is frequently associated with menstrual cycle alterations. In men, the effects of similar amounts of exercise are less well-studied. We tested the hypothesis that endurance exercise in men is also associated with alterations in reproductive function. We studied 12 marathon runners and 12 age-matched, lean controls; serum and semen samples were collected every 2 weeks for 12 weeks. Sperm counts, sperm morphologies, and mean levels of testosterone (T), free T, sex hormone binding globulin, cortisol, follicle stimulating hormone, and biologically active luteinizing hormone (LH) were similar in the two groups. Mean levels of immunologically active LH were somewhat higher in the marathoners. We conclude that this level of strenuous, long-term endurance exercise does not have major adverse effects on reproductive function in men. PMID- 2108060 TI - Serum bioactive and immunoreactive follicle-stimulating hormone in oligozoospermic and azoospermic men: application of a modified granulosa cell bioassay. AB - Serum follicle-stimulating hormone (FSH) levels measured by radioimmunoassay (RIA) usually correlate well with the rate of spermatogenesis. However, in certain cases this correlation does not exist. The purpose of this study was to establish a reliable bioassay of FSH for the andrological clinic. Follicle stimulating hormone was measured by both standard RIA and bioassay in 98 men subgrouped into normospermic, oligospermic, and azoospermic. Bioactivity of FSH was determined using in vitro cultures of granulosa cells utilizing progesterone measurements for assessing FSH activity. Results of FSH levels obtained by both methods correlated well (r = 0.55, P less than 0.01) within themselves, and both correlated negatively and significantly with sperm concentration. The ratio between bioactivity and immunoreactivity of FSH did not correlate with sperm density. Thus, the decrease in sperm concentration and other sperm variables resulting from a germinal epithelial dysfunction was not mediated or associated with low biological activity of FSH. The application of this method can be of clinical value in cases where a discrepancy is found between serum RIA-FSH levels and sperm quality. PMID- 2108061 TI - Luteinization to oocyte retrieval delay in women in whom multiple follicular growth was induced as part of an in vitro fertilization/gamete intrafallopian transfer program. AB - Different luteinization-to-oocyte-retrieval delays were examined in 64 IVF/GIFT patients. Multiple follicular stimulation was induced with combined therapy of hMG and GnRH-a to create continuous pituitary suppression and thus eliminate endogenous gonadotropin fluctuations. The results demonstrated that with this induction regime, the time interval can be extended to 39 hours without preoperative ovulation and with improved oocyte maturity. PMID- 2108062 TI - Gonadotropin stimulation for in vitro fertilization and embryo transfer in insulin-dependent diabetics: follicular response, oocyte quality, embryo development, and follicular environment. AB - Two IDD patients were stimulated with gonadotropins for IVF and ET. Both patients had high E2 response and greater than or equal to 5 preovulatory oocytes retrieved, normal fertilization and cleavage rates, and transfer; neither conceived. Follicular fluid showed levels of E2, P, A, hCG, and PRL similar to non-IDD. Epidermal growth factor could not be detected in FF. Insulin-dependent diabetes patients can undergo gonadotropin stimulation for IVF with customary responses. Their follicular milieu resembles that of non-IDD patients except for a lack of EGF. PMID- 2108063 TI - Interference with ovulation by sequential treatment with the antiprogesterone RU486 and synthetic progestin. AB - Seven healthy women were treated with the antiprogesterone RU486, 25 mg/d, on days 1 to 14 of the follicular phase of the menstrual cycle, followed by the synthetic progestin NET in the luteal phase of the cycle. Venous blood samples were collected twice per week. Serum E2, P, and RU486 concentrations were determined by RIAs, and FSH and LH by immunofluorometric assays. Ultrasonography was used to measure the sizes of the follicles. Serum concentrations of FSH and LH were not suppressed during the treatment. Ovulation was apparently suppressed during RU486 treatment according to E2 and P concentrations and ultrasonography findings. During NET treatment, some evidence of ovulation and follicle growth were found during the first treatment periods. During the third treatment cycle, there was no evidence of ovulation (n = 2). Estradiol concentrations were sufficient to stimulate normal proliferative growth of the endometrium during the treatment. Control of bleeding was good. The exact mechanism of action of RU486 on steroid synthesis and ovulation is not clear, but it appears to act at the ovarian level. The evidence indicates that sequential RU486/progestin treatment could be developed to result in suppression of follicular growth and ovulation. PMID- 2108064 TI - Leuprolide depot before myomectomy. PMID- 2108065 TI - Development of muscle fiber types in the prenatal rat hindlimb. AB - Immunohistochemistry was used to examine the expression of embryonic, slow, and neonatal isoforms of myosin heavy chain in muscle fibers of the embryonic rat hindlimb. While the embryonic isoform is present in every fiber throughout prenatal development, by the time of birth the expression of the slow and neonatal isoforms occurs, for the most part, in separate, complementary populations of fibers. The pattern of slow and neonatal expression is highly stereotyped in individual muscles and mirrors the distribution of slow and fast fibers found in the adult. This pattern is not present at the early stages of myogenesis but unfolds gradually as different generations of fibers are added. As has been noted by previous investigators (e.g., Narusawa et al., 1987, J. Cell Biol. 104, 447-459), all of the earliest generation (primary) muscle fibers initially express the slow isoform but some of these primary fibers later lose this expression. In this study we show that loss of slow myosin in these fibers is accompanied by the expression of neonatal myosin. This switch in isoform expression occurs in all primary fibers located in specific regions of particular muscles. However, in other muscles primary fibers which retain their slow expression are extensively intermixed with those that switch to neonatal expression. Later generated (secondary) muscle fibers, which are interspersed among the primary fibers, express neonatal myosin, although a few of them in stereotyped locations later switch from neonatal to slow myosin expression. Many of the observed changes in myosin expression occur coincidentally with the arrival of axons in the limb or the invasion of axons into individual muscles. Thus, although both fiber birth date and intramuscular position are grossly predictive of fiber fate, neither factor is sufficient to account for the final pattern of fiber types seen in the rat hindlimb. The possibility that fiber diversification is dependent upon innervation is tested in the accompanying paper (K. Condon, L. Silberstein, H.M. Blau, and W.J. Thompson, 1990, Dev. Biol. 138, 275-295). PMID- 2108066 TI - Differential expression of alternate forms of a Drosophila src protein during embryonic and larval tissue differentiation. AB - The Dsrc28C gene encodes two major proteins, p66 and p55, each of which contains a tyrosine kinase domain. Using monoclonal antibodies we have completed a detailed investigation of the spatial expression of Dsrc28C proteins during embryonic and larval development. Differentiation of a number of embryonic tissues is accompanied by the induction of Dsrc28C expression. With the exception of the developing salivary glands which express high levels of p66, developing tissues express the p55 form of Dsrc28C. Notable examples are cells of the and peripheral nervous systems which express p55 from the early stages of neurogenesis through the remainder of embryogenesis and pole cells which transiently express p55 during portions of embryonic stages 10 and 11. Nervous system expression includes the cell bodies and neuronal fibers of the central nervous system, the anterior sensory organs, and the peripheral sensory neurons. During larval development, p55 levels within the central nervous system remain high but substantial changes in the pattern of expression take place. p55 gradually disappears from the neuronal fibers of the central nervous system and from embryonic cell bodies. During the third larval instar, the birth of immature neuroblasts within the ventral and midbrain ganglia, but not within the optic ganglia, is marked by a transient high level of p55 expression. All imaginal cells that have been observed within the larva express the p66 protein. The patterns of expression that we have noted suggest that expression of the p55 form of Dsrc28C protein is an early event in the differentiation of neuronal cells, while expression of the p66 form is characteristic of cells committed to ectodermal cell differentiation. PMID- 2108067 TI - shibire, a neurogenic mutant of Drosophila. AB - Embryos of the temperature-sensitive mutant shibirets 1 were given short exposures to the restrictive temperature during the stage when neuroblasts segregate from the presumptive epidermis. The resulting lethal phenotype, expansion of the nervous system at the expense of the epidermis, is characteristic of a group of mutants called neurogenic mutants. Exposures as short as 20 min were sufficient to promote the neurogenic phenotype. Cell masses from heat-pulsed embryos could be cultured in vivo as tumorous masses which retained some characteristics of neural tissue. An examination of the neurogenic region from heat-pulsed embryos revealed numerous packets of extracellular vesicles and coated pits blocked in endocytosis. PMID- 2108068 TI - Islet mass and function in diabetes and transplantation. AB - The concept of pancreatic beta-cell mass is fundamental to the understanding of normal metabolism, the pathogenesis of diabetes, and the transplantation of beta cell tissue. The amount of beta-cell tissue present in the pancreas is a major determinant of the quantity of insulin that can be secreted, and its mass will vary according to the size of the individual and the degree of insulin resistance present. Not all insulin-producing cells are the same, and the dimensions of this heterogeneity remain to be defined. Pancreatic beta-cell mass is markedly reduced in insulin-dependent diabetes mellitus and moderately reduced in non-insulin dependent diabetes mellitus. In both forms of diabetes, there are qualitative and quantitative abnormalities of insulin secretion that cannot be explained entirely by changes in beta-cell mass. The amount of beta-cell tissue needed for successful transplantation has only been partially defined. Segmental (approximately 50% of the pancreas) transplantation can normalize plasma glucose levels in humans. Difficulty obtaining sufficient amounts of beta-cell tissue is expected to remain a barrier to successful islet transplantation for the immediate future. More should be learned about the function and fate of grafted islet cells. PMID- 2108069 TI - Comparison of cytokine effects on mouse pancreatic alpha-cell and beta-cell lines. Viability, secretory function, and MHC antigen expression. AB - Cytokine effects on permanent cell lines of transformed mouse pancreatic alpha- and beta-cells were compared. The beta-tumor cell 1 (beta TC1) line (from an adenoma created in transgenic mice expressing the SV40 large T-antigen oncogene under control of the rat insulin II promoter) produced insulin predominantly, although small quantities of intracellular glucagon (100:1 insulin to glucagon) were detectable by radioimmunoassay. The alpha TC1 line (from an adenoma created in transgenic mice expressing the SV40 large T-antigen oncogene under control of the rat preproglucagon promoter) produced not only glucagon but also considerable quantities of insulin (4:1 glucagon to insulin) and preproinsulin mRNA. We therefore cloned alpha TC1 cells and obtained 12 glucagon-producing clonal cell lines that did not produce levels of insulin detectable by radioimmunoassay. Analysis by Northern blotting of total RNA from two lines, alpha TC1 clones 6 and 9, confirmed the absence of preproinsulin mRNA. No somatostatin or pancreatic polypeptide was detected by immunohistochemical staining in alpha TC1 clones 6 or 9 or beta TC1 cells. Rat recombinant gamma-interferon (IFN-gamma; 5-250 U/ml) or mouse recombinant interleukin 1 (IL-1; 1-25 U/ml) individually inhibited DNA synthesis in beta TC1 cells after 3 days of treatment. The two cytokines in combination acted synergistically to further depress DNA synthesis and increase cytotoxicity. In contrast, alpha TC1 clone 9 cells were not sensitive to inhibition of DNA synthesis by each cytokine individually, although glucagon synthesis was inhibited. The combination of these cytokines caused marked inhibition of DNA and glucagon syntheses in alpha TC1 clone 9 cells. alpha TC1 clone 9 cells were somewhat more resistant to the cytotoxic action of the combined cytokines than were beta TC1 cells. Incubation with 50 U/ml IFN-gamma induced class II MHC molecules (I-Ab, I-Ad, and I-Ed) and enhanced the constitutive expression of class I molecules (H-2Kb and H-2Kd) on the cell surfaces of beta TC1, uncloned alpha TC1, and alpha TC1 clones 6 and 9. Thus, these cell lines are heterozygous for MHC alleles derived from both parental strains used in the construction of the transgenic mice [C57BL/6J (H-2b) and DBA/2J (H-2d)]. Class II gene transcription induced by IFN-gamma was confirmed in beta TC1 and alpha TC1 clone 9 cells by Northern blot analysis with A alpha-, A beta-, E alpha, and E beta-DNA probes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2108070 TI - Changes in skeletal muscle contractile properties in streptozocin-induced diabetic rats and role of polyol pathway and hypoinsulinemia. AB - Functional changes in slow-twitch soleus and fast-twitch extensor digitorum longus muscles were assessed after 2 mo of streptozocin-induced diabetes in rats. For soleus, there was a slowing of twitch times both for contraction and relaxation and a reduction of maximum tetanic relaxation rate. There was little effect on strength performance assessed by maximal tetanic tension production. Treatment with the aldose reductase inhibitor ponalrestat largely prevented relaxation defects but had little effect on contraction. For the fast muscle, twitch times were relatively unaffected, but maximum tetanic relaxation rate was reduced. In addition, tetanic tension output decreased. These changes were largely prevented by ponalrestat treatment. The effects of partial insulin therapy were also investigated. This regimen reduced hypoinsulinemia, but sufficient hyperglycemia remained to stimulate the polyol pathway. It prevented the slowing of soleus twitch contraction but had no effect on relaxation. For extensor digitorum longus, insulin produced further deleterious effects on tetanic tension and maximum relaxation rate, which were antagonized by ponalrestat. A 1% dietary myo-inositol supplement had little effect on contractile function in slow or fast muscles. It was concluded that polyol pathway activity is an important factor underlying skeletal muscle functional changes in diabetes, probably acting through disruption of Ca2+ handling. Hypoinsulinemia was considered a secondary factor causing atrophy, particularly of fast muscles. There was no evidence of effects dependent on neuropathy. PMID- 2108071 TI - Insulin independence after islet transplantation into type I diabetic patient. AB - Effective clinical trials of islet transplantation have been limited by the inability to transplant enough viable human islets into patients with type I (insulin-dependent) diabetes mellitus to eliminate their exogenous insulin requirement. We report the first type I diabetic patient with an established kidney transplant on basal cyclosporin immunosuppression who was able to eliminate the insulin requirement after human islet transplantation into the portal vein. We successfully isolated approximately 800,000 islets that were 95% pure from 1.4 cadaver pancreases containing 121 U of insulin. Islets were proven viable by in vitro insulin response to glucose challenge. After 7 days of 24 degrees C culture, the islets were transplanted into the portal vein under local anesthesia. Seven days of Minnesota antilymphoblast globulin (20 mg/kg) administration followed the islet transplantation, with maintenance of the cyclosporin. Blood glucose was kept under strict control via intravenous insulin for 10 days posttransplantation, when all insulin therapy was stopped. Off insulin, the average 24-h blood glucose level remained less than 150 mg/dl, with the fasting glucose level at 115 +/- 6 mg/dl and the 2-h postprandial level at 141 +/- 8 mg/dl for 22 days posttransplantation (the time of this study). The C peptide values post-Sustacal testing, although initially rising slower, exceeded the normal range, with peak values of 1.0-1.8 pmol/ml. This preliminary result represents the first essential step required to determine the feasibility of islet transplantation by future clinical trials. PMID- 2108072 TI - Reversal of diabetes in BB rats by transplantation of encapsulated pancreatic islets. AB - Prolonged survival of pancreatic islet allografts implanted in diabetic BB rats was achieved by encapsulation of individual islets in a protective biocompatible alginate-polylysine-alginate membrane without immunosuppression. Intraperitoneal transplantation of the encapsulated islets reversed the diabetic state of the recipients within 3 days and maintained normoglycemia for 190 days. Normal body weight and urine volume were maintained during this period, and no cataracts were detected in the transplant recipients. In contrast, control rats receiving transplants of unencapsulated islets experienced normoglycemia for less than 2 wk. These results demonstrated that microencapsulation can protect allografted islets from both graft rejection and autoimmune destruction without immunosuppression in an animal model that mimics human insulin-dependent diabetes. PMID- 2108073 TI - Changes in Sertoli cell function in vitro induced by nitrobenzene. AB - Nitrobenzene (NB) has been identified as a testicular toxicant in vivo, but its site of action remains unknown. In the present study, the effect of NB on the Sertoli cell was assessed in vitro using Sertoli cell and Sertoli-germ cell cocultures. The parameters measured were the exfoliation of germ cells; the secretion of lactate, pyruvate, and inhibin; and gross cellular morphology. The effect of metadinitrobenzene (mDNB), a related compound which is a known Sertoli cell toxicant, was assessed for comparison. Gross morphological changes including vacuolation of Sertoli cells were observed following treatment of cultures with 10(-3) M NB. Exposure of cocultures to NB also resulted in dose-dependent exfoliation of predominantly viable germ cells. NB (greater than 5 X 10(-4) M) and mDNB at the single dose level used (10(-4) M) stimulated the secretion of lactate and pyruvate significantly by Sertoli cells, an effect that was more marked in the absence of germ cells. Comparable changes were observed in follicle stimulating hormone (FSH)-stimulated cultures. Inhibin secretion by Sertoli cells was also altered by exposure to NB but in a biphasic manner, with low (10(-8) to 10(-6) M) and high (10(-4) to 10(-3) M) doses enhancing inhibin secretion while intermediate (10(-5) M) doses had no effect. These effects were evident in both culture systems but inhibin secretion by Sertoli-germ cell cocultures was always greater than that by Sertoli cell cultures. However, these effects of NB on inhibin secretion were not evident in FSH-stimulated cultures. In contrast to the effects of NB, mDNB had no effect on basal secretion of inhibin but blocked the stimulatory effect of FSH. It is concluded that NB, like mDNB, is probably a Sertoli cell toxicant in view of its similar disruptive effects on various parameters of Sertoli cell function. However, NB is far less toxic than mDNB at equivalent concentrations in vitro. The present study is the first to evaluate the potential of inhibin secretion by Sertoli cells in culture as an additional marker of toxicant action, and concludes that it merits further study in this context. PMID- 2108074 TI - Specificity of molecular changes in neurons involved in memory storage. AB - Evidence implicating molecular steps in memory storage is discussed, particularly with reference to molecular specificity and uniqueness and the possible relevance of these steps to other types of long-lasting transformations such as those of development, regeneration, and tumorigenesis. The role of protein kinase C mediated phosphorylation of identified protein subtrates, such as a 20,000-dalton GTP-binding protein, is described for associative memory of the snail Hermissenda, associative conditioning of the rabbit, and long-term potentiation. Cyclic AMP-mediated phosphorylation during sensitization of the snail Aplysia is also examined. PMID- 2108075 TI - [Residual endometriosis following LHRH analog therapy]. AB - LHRH analogue therapy has proved effective in the treatment of endometriosis. Although in the majority of patients a marked reduction in AFS implant score is observed, in some cases residual endometriotic foci are macroscopically suspected and can be confirmed by histological examination during a second check operation at the end of treatment. In the study presented, 34 patients from 69 showed residual endometriosis after a 6 months' treatment with the LHRH analogue buserelin (900 mcg/d intranasally). According to light microscopical criteria regressive changes were seen in 52% of the implanted patients, nevertheless 29% presented with proliferative elements of the disease. In 19% proliferation and regression were seen in the same biopsy or even in the same gland. Histology did not relate to either the degree of ovarian suppression by LHRH analogue therapy, or to the location of the residual endometriotic foci. These results add another piece of evidence to the fact, that endometriosis presents itself as a heterogenic disorder. In addition, susceptibility to a hormonal ablative therapy rather depends on the degree of dysontogenetic differentiation, than on the completeness of induced ovarian suppression. PMID- 2108076 TI - Bismuth subsalicylate reduces peptic injury of the oesophagus in rabbits. AB - Bismuth subsalicylate was tested in an in vivo perfused rabbit model of oesophagitis for its ability to prevent the mucosal injury caused by pepsin. Treatment efficacy was assessed under both a treatment-before-injury protocol and a treatment-after-injury protocol. Oesophageal mucosal barrier function was evaluated by measuring flux rates of H+, K+, and glucose. The degree of oesophagitis was determined by gross and microscopic examination of the mucosa by several independent observers. Results showed that under both treatment protocols, bismuth subsalicylate significantly reduced the pepsin induced disruption of the mucosal barrier, as well as the morphologic changes. Bismuth subsalicylate when given after exposure to pepsin was also found to protect against the morphologic injury in a dose dependent manner. Experiments in vitro suggested that bismuth subsalicylate inhibits the proteolytic action of pepsin by interacting with pepsin, rather than with the pepsin substrate. We conclude that bismuth subsalicylate can protect the oesophageal mucosa against peptic injury, probably through inactivation of pepsin. PMID- 2108078 TI - Raised histamine concentrations in chronic cholestatic liver disease. AB - Pruritus is a frequent symptom in chronic cholestatic liver disease. To date, no single causative mechanism has been identified. We examined venous plasma concentrations of the known pruritogen, histamine, using a highly sensitive radioenzymatic assay in 42 patients with chronic cholestatic liver disease, and in normal controls. The mean plasma histamine level was significantly greater in chronic cholestatic liver disease patients (275 (117) pg/ml; X (SD) than in controls (140 (72) pg/ml, n = 20) (p less than 0.0001). No significant differences were found between histamine concentrations in the two chronic cholestatic liver disease subgroups: primary biliary cirrhosis and sclerosing cholangitis. Histamine concentrations were significantly greater (p less than 0.01) in the pruritic (319 (132) pg/ml) as compared with the non-pruritic (227 (75) pg/ml) chronic cholestatic liver disease patients. The histaminase activity was equivalent in patients and controls. The finding of raised histamine concentrations in chronic cholestatic liver disease suggests in vivo mast cell activation and a potential role for its mediators in the pruritus characteristic of these disorders. PMID- 2108077 TI - Factors affecting the potassium concentration at the mucosal surface of the proximal and the distal colon of guinea pig. AB - K+ concentrations were measured in vitro with K+ sensitive microelectrodes in the microclimate at the luminal cell surface of the colon of guinea pigs. The serosal K+ concentration was mostly 5.4 mmol/1, the mucosal K+ concentrations were changed (0, 5, 50, or 70 mmol/l). Under control conditions K+ concentrations in the microclimate of the proximal colon were also low (6-9 mmol/l) and rather independent from K+ concentrations in the bulk luminal solution. In the distal colon K+ concentrations in the microclimate increased from 3.7 mmol/l when no K+ was in the luminal solution, up to 22 mmol/l when the mucosal K+ concentrations was 70 mmol/l. Attempts to decrease K+ conductance of the apical membrane with Ba++, to impair K+ transport with ouabain and to increase the paracellular shunt with deoxycholic acid did not affect K+ concentrations in the microclimate of the proximal colon but decreased K+ concentrations in the distal colon. When valinomycin or triaminopyrimidine were added to the mucosal solution at high K+ concentrations in the luminal solutions the K+ concentration in the microclimate was raised. At low luminal K+ concentrations valinomycin had no effect, triaminopyrimidine significantly diminished K+ concentrations at the cell surface. Regional differences in paracellular shunt conductance and in the preepithelial diffusion barrier are thought to be responsible for the observed differences between the proximal and the distal colon. Obviously, however, further unknown mechanisms have to be involved. PMID- 2108079 TI - A phase I clinical trial of intraperitoneal thiotepa for refractory ovarian cancer. AB - Treatment options for patients with ovarian cancer who have failed systemic and intraperitoneal (ip) cisplatin-based chemotherapy are limited. We conducted a phase I clinical study of ip thiotepa in patients with refractory ovarian cancer to determine the maximum tolerated dose (MTD). Ten patients were given 39 courses of thiotepa (median number of courses per patient, 3.5; range, 1-10+). All patients had received prior ip cisplatin; 7 also had received iv cisplatin, and 5 had three or more prior regimens. Thiotepa (30-80 mg/m2) was given ip in 2 liters normal saline every 4 weeks. The therapy was well tolerated. There was no vomiting, stomatitis, alopecia, or peritonitis. The dose-limiting toxicity was myelosuppression. With repeated doses, patients had a delayed marrow recovery and required a 1- to 2-week delay in treatment. Six patients had stable disease (duration 2-14+ months; median duration 5 months); 1 patient had a 50% decrease in CA-125 level, and 1 patient with no measurable disease remained clinically disease-free. In summary, ip thiotepa had clinical activity in heavily pretreated patients with refractory ovarian cancer with disease stabilization seen in 6 of 9 evaluable patients and a partial response seen in 1 patient. Myelosuppression was the only toxicity encountered. A dose of 60 mg/m2 ip is recommended for phase II studies. PMID- 2108080 TI - Immunohistochemical evidence for human immunodeficiency virus-1 infection of liver Kupffer cells. AB - To investigate the possibility of human immunodeficiency virus-(HIV) 1 infection of liver cells, liver samples from 17 patients with either acquired immunodeficiency syndrome (AIDS, 13), AIDS-related complex (ARC, 3), or lymphadenopathy syndrome (LAS, 1) were studied. A monoclonal antibody directed against the p24 gag HIV-1 protein was used in an immunoperoxidase assay and yielded positive results in seven out of 17 samples. Staining by anti-p24 antibody was of three types: diffuse in Kupffer cells of most samples, inside granuloma in cells that were probably histiocytes, and in some sinusoidal cells whose origin was difficult to ascertain. Attempts to locate the CD4 membrane antigen showed that it was mainly present on endothelial sinusoidal cells. These results indicate that liver cells, including Kupffer cells, might be infected by HIV-1, and that these cells might be involved in certain liver lesions observed during HIV-1 infection, particularly sinusoidal abnormalities. PMID- 2108081 TI - Pasteurella multocida infections in mice with reference to haemorrhagic septicaemia in cattle and buffalo. AB - Haemorrhagic septicaemia (HS) is an infectious disease of cattle and buffalo caused by particular serotypes of Pasteurella multocida and is one of the most economically important livestock diseases in South-East Asia. While HS has been recognized for many years, very little is understood about the disease, primarily because of the expense of cattle and a lack of suitable animal models. The suitability of using mice to study HS was assessed using parameters such as the critical pathogenic dose, kinetics of infection, pathology of disease and resistance to reinfection. Pasteurella multocida M1404, the type strain for Carter group B, the serotype responsible for Asian HS, was injected intraperitoneally into BALB/c mice. As few as 20 colony forming units produced an overwhelming septicaemia in mice in less than 30 h. The kinetics of infection demonstrated a very rapid in vivo multiplication rate. There was no evidence of inhibition of bacterial cell growth by natural host defence mechanisms, even with the very small inocula used. The gross pathology of the disease in mice was characterized by splenomegaly, lymphadenopathy and petechial haemorrhages similar to that observed in cattle and buffalo with HS. Mice were found to develop a short-lived resistance to reinfection following a primary infection which had been successfully treated with antibiotics. The mouse would seem to provide an ideal tool by which to study HS, but warrant further studies in order to be able to critically assess it as a model for this economically important disease. PMID- 2108082 TI - Evidence for differentiation of NK1+ cells into cytotoxic T cells during acute rejection of allogeneic bone marrow grafts. AB - The ability of lethally irradiated C57BL/6 mice to acutely reject H-2d bone marrow is due to a lymphocyte population that is NK1+, ASGM1+, CD4-, CD8-, CD3+. Transfer of spleen cells from C57BL/6 mice expressing these antigens into nonresponder 129 mice adoptively transfers the ability to reject H-2d marrow grafts. The specificity of this rejection maps to the H-2D major histocompatibility complex (MHC) region. Transplantation of high doses of H-2d marrow into C57BL/6 overrides the acute rejection mechanism leading to graft survival. During growth of the graft, a cytolytic activity develops that is due to ASGM1+, CD8+ cytolytic T lymphocytes (CTLs) with H-2Ld specificity. The possibility that the ASGM1+, CD8+ CTLs are descendents of the CD3+, NK1+, ASGM1+, CD8- cells responsible for acute rejection is investigated by adoptive cell transfer experiments. We show that beige mice that lack NK1+ cells as well as the ability to acutely reject H-2d marrow fail to generate specific CTLs after transplantation with a high dose of H-2d marrow. Transfer of highly purified NK1+ cells from B6.PL-Ly-2a/Ly-3a (Lyt-2.1) into beige mice together with H-2d marrow leads to generation of Lyt-2.1 CTLs from donor NK1+ cells. These results show that specific CTLs are generated from NK1+ cells during acute marrow graft rejection. PMID- 2108083 TI - Decreased cytosolic calcium and prostaglandin synthesis in prehypertensive rats. AB - The capacity of cultured renal medullary interstitial cells derived from Dahl salt-sensitive and salt-resistant rats to synthesize prostaglandin E2 (PGE2) was compared. Basal and arginine vasopressin (AVP)-induced PGE2 production by interstitial cells from salt-resistant rats was fourfold to fivefold higher than corresponding values of those from the salt-sensitive rats. Similarly, basal and AVP-responsive release of [3H]arachidonate were twofold higher by interstitial cells from salt-resistant compared with salt-sensitive rats. Differences in PGE2 production were abolished by the calcium inophore A23187 or the addition of exogenous arachidonate. The latter findings suggested a role for altered availability of endogenous arachidonate, possibly mediated by reduced calcium responsive lipase activity. Basal and AVP-induced increases in cytosolic free calcium concentration, assessed by the aequorin method, were significantly lower in interstitial cells from salt-sensitive versus salt-resistant rats, further supporting a possible role for altered cellular calcium homeostasis. Studies of the potential contribution of various phospholipases and of triglyceride lipase to the release of arachidonate for PGE2 synthesis in interstitial cells implicated phospholipase A2 activity as a major pathway. When assessed in vitro in cell cytosolic fractions at identical calcium concentration, phospholipase A2 activity was lower in interstitial cells from salt-sensitive versus salt resistant rats. Thus, both reduced cytosolic free calcium and phospholipase A2 activity of interstitial cells from salt-sensitive rats may contribute to the diminished capacity of these cells to liberate endogenous arachidonate for PGE2 synthesis. PMID- 2108084 TI - Effect of environmental conditions on production of toxic shock syndrome toxin 1 by Staphylococcus aureus. AB - The kinetics of toxic shock syndrome toxin 1 (TSST-1) production by Staphylococcus aureus was studied in a fermentor in which aeration rate, atmospheric composition, pH, and temperature were controlled. The toxin was synthesized at a maximal rate during the exponential phase. High bacterial populations were not necessarily accompanied by high TSST-1 yields. Aerobiosis increased TSST-1 production, but excessive aeration had an adverse effect. Addition of CO2 enhanced TSST-1 yield by increasing toxin production rate and efficiency. Cultures with no pH control made more TSST-1 than those maintained at pH 5.5 to 7.5. Maximum TSST-1 yields were obtained when cultures were supplied with air (20 cm3/min) and CO2 (5 cm3/min) via a sintered glass sparger. PMID- 2108085 TI - Growth-dependent alterations in production of serotype-specific and common antigen lipopolysaccharides in Pseudomonas aeruginosa PAO1. AB - Pseudomonas aeruginosa PAO1 was grown in various media and at different temperatures, and the heterogeneity of the extracted lipopolysaccharide (LPS) was characterized by polyacrylamide gel electrophoresis. The size distributions of the serotype-specific LPS and the common antigen LPS were analyzed on Western blots (immunoblots). Cells grown at high, near-growth-limiting temperatures, at low pH, in low concentrations of phosphate, or in high concentrations of NaCl, MgCl2, glycerol, or sucrose produced decreased amounts of the very long chain population of O-antigen LPS molecules. Lower temperatures and lowered glycerol, lowered sucrose, low sulfate, lower salt concentrations, and elevated pH did not significantly affect the level of this LPS population. The size and amount of common antigen LPS was either unaffected or increased slightly when the cells were grown under the above stress conditions. Cells grown under normal, nonstressed conditions were agglutinated only by serotype-specific antibodies. In contrast, cells grown under stress conditions, in which the long-O-polymer LPS was absent, were agglutinated by both serotype-specific and common antigen specific antibodies. The results indicate that the long O polymers cover and mask the shorter common antigen. However, specific growth conditions limit the production of the long O polymer, allowing the exposure and reactivity of the common antigen on the cell surface. PMID- 2108086 TI - Intracellular and cell-to-cell spread of Listeria monocytogenes involves interaction with F-actin in the enterocytelike cell line Caco-2. AB - Listeria monocytogenes penetrates and multiplies within professional phagocytes and other cells such as the Caco-2 human enterocytelike cell line. Listeriolysin O, a membrane-damaging cytotoxin accounts for intracellular multiplication through lysis of the membrane-bound phagocytic vacuole. This work demonstrates that once released within the cytosol, L. monocytogenes acquires the capacity to spread intracellularly and infect adjacent cells by interacting with host cell microfilaments. Such evidence was obtained by using drugs which disrupt the cell cytoskeleton. Nocodazole, which blocks polymerization of microtubules, did not affect intracellular spread, whereas cytochalasin D, which blocks polymerization of G-actin, inhibited the intracellular motility of the bacteria. By using fluorescence staining with 7-nitrobenz-2-oxa-1,3-diazole-phallacidin (NBD phallacidin), transmission electron microscopy, and immunogold labeling, direct evidence was obtained that intracellular bacteria were enveloped with a thick layer of F-actin. Within 2 h after entry, it was demonstrated by confocal microscopy that bacteria were following highly organized routes corresponding to stress fibers. Four hours after entry, some bacteria presented random movements which could be seen by the presence of a large trail of F-actin. Such movements also caused protrusions which deeply penetrated adjacent cells and resulted in the formation of vacuoles limited by a double membrane. After subsequent lysis of these membranes, bacteria released within the cytoplasm were able to multiply and invade new cells. In contrast, an hly::Tn1545 mutant of the wild-type microorganism demonstrated almost no intracellular spread. Only a few bacteria displaying delayed lysis of the phagocytic vacuole behaved like the wild-type strain. Hemolysin-mediated lysis of the phagocytic vacuole and subsequent interaction with host cell microfilaments may represent a major virulence factor allowing tissue colonization during listeriosis. PMID- 2108087 TI - Augmentation of GG2EE macrophage cell line-mediated anti-Candida activity by gamma interferon, tumor necrosis factor, and interleukin-1. AB - The expression of anti-Candida activity in the GG2EE macrophage cell line, generated by immortalization of fresh bone marrow with v-raf and v-myc oncogenes, was studied. GG2EE cells spontaneously inhibited the growth of an agerminative mutant of Candida albicans in vitro. The anti-Candida activity was maximal after 8 h of coculture and was proportional to the effector-to-target ratio. Gamma interferon (IFN-gamma), interleukin-1 (IL-1), and tumor necrosis factor (TNF) all significantly enhanced the anti-Candida activity of GG2EE cells. In contrast, IL 3, IL-4, and colony-stimulating factor 1 were ineffective. The augmentation of anti-Candida activity was not always concomitant with enhancement of phagocytosis, since IFN-gamma and colony-stimulating factor 1, but not IL-1 or TNF, augmented the phagocytic ability of GG2EE cells. Furthermore, the augmentation of anti-Candida activity in GG2EE cells did not correlate with the acquisition of antitumor activity. In fact, none of the cytokines alone were able to induce antitumor activity in GG2EE cells, which, however, could be activated to a tumoricidal stage by IFN-gamma plus heat-killed Listeria monocytogenes. These findings demonstrate that GG2EE cells exhibit spontaneous anti-Candida activity and that such activity is enhanced by TNF, IL-1, and IFN-gamma. PMID- 2108088 TI - Monoclonal antibodies to outer membrane protein PII block interactions of Neisseria gonorrhoeae with human neutrophils. AB - Nonopsonic binding of gonococci to human neutrophils appears to be mediated by a family of heat-modifiable outer membrane proteins termed protein IIs (PIIs). We studied the ability of a wide variety of antigonococcal monoclonal antibodies (MAbs) to inhibit the interactions of nonpiliated PII+ gonococci with human neutrophils by measuring gonococcal adherence to neutrophils and subsequent luminol-enhanced neutrophil chemiluminescence. From one set of 95 MAbs reacting with whole gonococci, only two, 7VA2 and 7B9, inhibited the ability of gonococci to induce neutrophil chemiluminescence. 7VA2 and 7B9 both reacted only with PII. MAb 53C4, from a smaller set of anti-PII MAbs, inhibited adherence to neutrophils of PII variants that bound 53C4, but not of PII variants that did not. It also inhibited gonococcus-induced neutrophil chemiluminescence. Using a whole-cell binding assay and Western blotting (immunoblotting), we showed that MAb 53C4 bound to one PII (PII4) of strain F62 and to two PIIs (PIIb and PIId) of strain FA1090. The present studies confirm and extend the role of PII in gonococcal adherence to and stimulation of human neutrophils and show intrastrain conservation of PII epitopes. The results indicate that PII is the only outer membrane component involved in adherence of nonpiliated gonococci to human neutrophils. PMID- 2108089 TI - Ability of mononuclear phagocytes from cattle naturally resistant or susceptible to brucellosis to control in vitro intracellular survival of Brucella abortus. AB - The role of bovine mammary macrophages and peripheral blood monocyte-derived macrophages in natural resistance to bovine brucellosis was evaluated. A group of 11 naturally resistant and 10 chronically infected susceptible cows was studied following challenge with Brucella abortus. Macrophages from a greater proportion (P less than 0.026) of naturally resistant cows were significantly superior to macrophages from susceptible cows in their ability to inhibit the in vitro intracellular replication of B. abortus after challenge exposure. Studies of a second group of cows used mammary macrophages from 12 heifers and blood monocyte derived macrophages from 22 bulls and heifers. These tests were completed before exposure to B. abortus, using mammary macrophages (P less than 0.039) and blood monocyte-derived macrophages (P less than 0.045), and also showed that macrophages from naturally resistant cattle were significantly superior in their ability to control the in vitro intracellular replication of B. abortus. Our data indicate that the mononuclear phagocytes from more than 80% of the resistant cattle controlled intracellular replication of B. abortus significantly better than did mononuclear phagocytes from susceptible cattle. Mononuclear phagocyte function appears to be an important factor in determining natural resistance to bovine brucellosis. PMID- 2108090 TI - Causative agent of spotted fever group rickettsiosis in Japan. AB - Since 1984, it has been known that spotted fever group rickettsiosis exists in Japan. We isolated three strains of the causative rickettsiae, designated Katayama, Misaka, and Abe, from patients with the disease and studied the characteristics of the isolates. Nude mice and cyclophosphamide-treated mice died after infection with the isolates. However, infected normal mice recovered and acquired immunity. Infected adult male guinea pigs had fever, a scrotal reaction, and seroconversion. The isolates propagated well in tissue-cultured Vero cells. Analysis by the cross-immunofluorescence antibody method showed that these isolates were closely related serologically. To reveal their immunological properties in detail, we produced 21 anti-Katayama monoclonal antibodies. Seven of these antibodies reacted with all representative strains of spotted fever group rickettsiae used in this study, and five others reacted only with the homologous strain, revealing that the Katayama strain has a strain-specific antigen(s) different from those of other spotted fever group rickettsiae. Moreover, these strain-specific antibodies also reacted with the Misaka and Abe strains. These results demonstrate that the causative agent of spotted fever group rickettsiosis in Japan is a new serotype of spotted fever group rickettsiae. PMID- 2108091 TI - Antibody enhances killing of Tritrichomonas foetus by the alternative bovine complement pathway. AB - The role of bovine antibody and complement in host defense against Tritrichomonas foetus was measured by using an assay of trichomonad viability based on protozoal uptake of tritiated adenine. Moderate killing was measured in the absence of antibody only with high concentrations of complement-preserved hypogammaglobulinemic bovine serum. However, very low concentrations of hyperimmune serum promoted significant enhancement (P less than 0.05) of killing by complement. Heat inactivation of complement (56 degrees C for 30 min) eliminated antibody-dependent and -independent killing. Similarly, depletion of bovine factor B in serum by heat treatment (50 degrees C for 45 min) abolished antibody-dependent and -independent killing. However, selective inactivation of the classical complement pathway with magnesium ethylene glycol-bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid did not affect antibody-dependent or -independent killing by complement. These findings demonstrate antibody enhancement of complement-mediated killing of T. foetus by the alternative pathway of bovine complement. PMID- 2108092 TI - New mouse models for chronic Cryptosporidium infection in immunodeficient hosts. AB - Cryptosporidium sp. causes fulminant diarrhea and chronic infection in immunocompromised, particularly human immunodeficiency virus-infected, persons. The lack of in vitro cultivation and a suitable animal model has limited development of effective treatment. We describe two new mouse models of chronic symptomatic cryptosporidiosis in adult athymic mice and in T-cell subset-depleted mice. A progressive infection, fatal within 4 months, occurred in most adult athymic mice; a few developed stable infections. Symptoms included dehydration, weight loss, intermittent diarrhea, and jaundice. Pathologic abnormalities and organisms localized in the intestine in stable infections but involved the hepatobiliary tree and pancreas in others. Lymphoid cells from histocompatible, Cryptosporidium sp.-immune mice cured infected nude mice. Identical infections occurred in neonatally infected BALB/c mice treated with anti-CD4 monoclonal antibodies alone or also with anti-CD8 monoclonal antibodies; the mice were cured when the monoclonal antibody treatments were stopped. These models will be useful in definition of the immune defects that permit chronic cryptosporidiosis to develop and in assessment of treatment modalities. PMID- 2108093 TI - Induction of interleukin-1 from murine peritoneal macrophages by Pseudomonas aeruginosa exotoxin A. AB - Pseudomonas exotoxin A, an ADP-ribosylating toxin produced by Pseudomonas aeruginosa, has been shown to stimulate the proliferation of murine thymocytes, which requires the participation of accessory cells. This requirement for accessory cells can be replaced by supernatant from adherent peritoneal exudate cells that have been stimulated with exotoxin A. Antibody to exotoxin A inhibits the induction of the thymocyte mitogenic activity from adherent peritoneal macrophages. However, antibody to exotoxin A had no effect on the thymocyte proliferation if the antibody was added to supernatant which contained thymocyte mitogenic activity. The thymocyte mitogenic activity was associated with a protein or protein complex with a molecular mass of greater than 10,000 daltons. D10 bioassays indicated the presence of interleukin-1 (IL-1) in the supernatant. Antibody to IL-1 inhibited the ability of supernatant to induce thymocytes to proliferate. Therefore, these data suggest that Pseudomonas exotoxin A can stimulate the production of IL-1 from adherent peritoneal cells, which induces murine thymocytes to proliferate. PMID- 2108094 TI - Biochemical and biological activities of recombinant S1 subunit of pertussis toxin. AB - degP-deficient strains of Escherichia coli grown in M-9 medium supplemented with ZnCl2 expressed the recombinant S1 subunit of pertussis toxin (rS1) in a form electrophoretically identical to the authentic S1 subunit. Subcellular fractionation showed that the full-length form of rS1 was membrane associated, while proteolytic fragments of rS1 were present in the periplasm. rS1 was extracted from outer membrane preparations with 8 M urea and purified by gel filtration chromatography. Purified rS1 ADP-ribosylated transducin at a similar molar efficiency relative to authentic pertussis toxin and, when associated with the native B oligomer of pertussis toxin, elicited Chinese hamster ovary cell clustering. PMID- 2108095 TI - Increased 137caesium whole body radioactivity in high-performance athletes. AB - A shadow shield whole body counter with automated gamma spectrum analysis is used in the division of nuclear medicine for the measurement of whole body radioactivity. After the radioactive fall-out in Austria caused by the Chernobyl accident the instrument has been extensively utilized for the assessment of the radiation level in the general population. In November of 1986 and 1987 the level of internal contamination with 137Cs in high-performance athletes was compared with a group of subjects practicing little or no sports. It was found that significantly higher contents of 137Cs were present in the athletes. Furthermore, it was found that within the groups of athletes male subjects had significantly higher internal 137Cs contamination per kilogram of body mass than the female subjects. An explanation for this is the different nutrition and the higher relative muscle mass of the athletes. PMID- 2108096 TI - The synthesis and role of integrin in corneal epithelial cells in culture. AB - Cell-substratum interaction and recognition is essential for cellular adherence and protein synthesis. To understand the mechanisms underlying diseases related to corneal erosion, it is necessary to examine the role integral proteins play in cellular adherence and spreading. In the current study, we used antibodies to evaluate the accumulation of integrin by corneal epithelial cells in tissue culture. We demonstrated that while the protein was incorporated into the cell layer at 6, 24, 48, and 72 hr, a far greater amount was secreted into the media. The total amount of integrin did not change with time, and the level of mRNA did not increase from 24 to 48 hr. During this time period, fibronectin was not detected. Antibodies to the fibronectin-binding receptor inhibited cellular spreading over a period of 18 hr. These results indicate that rabbit corneal epithelial cells do synthesize integrin and that integrin plays a critical role in cellular spreading. PMID- 2108097 TI - The Nancy Cruzan case. PMID- 2108098 TI - Improving prenatal care. PMID- 2108099 TI - Is the continued provision of food and fluids in Nancy Cruzan's best interests? PMID- 2108100 TI - In the Supreme Court of the United States. No. 88-1503. Nancy Beth Cruzan, by her parents and co-guardians, Lester L. Cruzan, et ux., petitioners, v. Director, Missouri Department Health, et al. PMID- 2108101 TI - In the matter of Arnold Shumosic. PMID- 2108102 TI - Cost-benefit analysis of routine mumps and rubella vaccination for Israeli infants. AB - Until January 1989, mumps vaccine was not routinely administered in Israel, and rubella immunization was restricted to adolescent girls. The theoretical effect of combined mumps-rubella vaccination was applied to a population consisting of a cohort of 1-year-old children followed for 13 years. Assuming 90% compliance and 95% vaccine efficacy, projected clinical cases of mumps, rubella, encephalitis and thrombocytopenia would be reduced by 4,144; 3,109; 13; and 1 respectively. We anticipate a benefit to cost ratio of between 1.17 and 1.77 for the program. Since only 10-20% of cases are reported, the true benefit to cost ratio is likely to be at least 5.85. The benefit to cost ratio based on health service benefits alone is between 0.34 and 0.52; however, after adjusting for under-reporting, benefits are expected to exceed costs. Expenditures for laboratory testing, a factor not previously considered in such an analysis, would be reduced by approximately $2,750 per year. These results justify the initiation in January 1989 of nationwide routine vaccination. PMID- 2108103 TI - Parental responsibility and the Infant Bioethics Committee. PMID- 2108104 TI - Functional capacity and mental status of elderly people in long-term care in west Glasgow. AB - Functional capacity and mental status were assessed in 821 patients in long-term care in West Glasgow. In geriatric medical long-term care only five (1.3%) out of 387 patients were independent in activities of daily living (walking, transfers from bed and chair, dressing, toileting, urinary and faecal continence) and were not severely mentally impaired (AMT score greater than 6/10); in psychogeriatric care n = 6/143 (4.2%) in private nursing homes n = 6/66 (9.1%) and in residential care n = 100/235 (42.6%). Patients in geriatric medical care had a greater prevalence of immobility and urinary incontinence but less mental impairment than those in psychogeriatric care. Nearly all patients placed in geriatric medical or psychogeriatric care had major functional disability or mental impairment. The level of disability was less in private nursing than in geriatric medical care. Although 57% of those in residential care required some assistance or supervision in activities of daily living or had severe mental impairment, 86% were independent in walking and 83% were continent of urine. The implications of these findings for the provision of care for physically and mentally frail elderly are discussed. PMID- 2108105 TI - Effect of normobaric oxygen on tumor radiosensitivity: fractionated studies. AB - The sensitizing ability of 100% normobaric oxygen was investigated in a mouse mammary carcinoma (CaNT) using a variety of fractionated regimens. Both regrowth delay and local control were used as assays of tumor response. With both assays, there was a similar and significant increase in radiosensitivity for all fractionated schedules. Enhancement ratios ranged from 1.24 to 1.45, the highest increase being observed with a 30 fraction schedule given in an overall time of 6 weeks. Thus, in CaNT tumors normobaric oxygen is a far more efficient radiosensitizer in fractionated treatments than the oxygen-mimetic compound misonidazole; an oxygen effect being observed at doses per fraction as low as 1.8 Gy. These results suggest strongly that normobaric gases could play an important role in the clinical management of tumors where hypoxia may limit the outcome of radiotherapy. PMID- 2108106 TI - Perinatal Health Belief Scales. A cost-effective technique for predicting prenatal appointment keeping rates among pregnant teenagers. AB - This study was designed to test two different methods for predicting pregnant teenagers at risk for failing to keep appointments for comprehensive prenatal care. Sixty-three pregnant adolescents completed psychological questionnaires assessing depression, social support, and life events. They and their primary health care provider also completed the Perinatal Health Belief Scales (PHBS) measuring the respondent's perception of risk and need for services. Following their infant's birth, adolescents completed a measure of health care satisfaction. Chart reviews provided data regarding birth weight, gestational age, Apgar scores, and appointment-keeping information. The results suggest that adolescents who failed to keep the most appointments were likely to have significantly lower levels of concern regarding their risks during pregnancy than their primary health care provider. Adolescents were more likely to keep appointments if they expressed levels of concern on the PHBS that were similar to their health care provider. The psychological measures and PHBS when applied individually, were not successful in predicting those with the greatest likelihood for nonadherence to appointments. PMID- 2108107 TI - Health care expenditure patterns for adolescents. AB - Health care expenditure patterns are described using a sample of 2,767 adolescents aged 10 to 18 years from the National Medical Care Utilization and Expenditure Survey. Average total per capita health care expenditures were $525. Average out-of-pocket expenses were $151 in 1988 dollars. The burden of out-of pocket expenses was distributed unevenly among the families of adolescents. The 10% of adolescents with the highest expenses accounted for 65% of all out-of pocket expenses. The presence of health insurance coverage greatly reduced the risk of incurring burdensome out-of-pocket expenses. Health policy interventions to improve health insurance coverage of adolescents are discussed. PMID- 2108108 TI - Use of gonadotropin-releasing hormone for hastening ovulation in transitional mares. AB - Natural GnRH and its analog have potential for hastening ovulation in mares. A study was conducted to evaluate the efficacy of a GnRH agonist given either as an injectable or s.c. implant for induction of ovulation in mares. Forty-five seasonally anestrous mares (March) were assigned to one of three groups (n = 15/group): 1) untreated controls; 2) i.m. injection of the GnRH agonist buserelin at 12-h intervals (40 micrograms/injection for 28 d or until ovulation) and 3) GnRH agonist administered as a s.c. implant (approximately 100 micrograms/24 h for 28 d). Six mares per group were bled on d 0, 7, 14 and 21 after injection or insertion of implant. Samples were taken at -1, -.5 and 0 h and at .5, 1, 1.5, 2, 4, 6 and 8 h after GnRH. Additional daily samples were drawn for 28 d after injection or until ovulation. Samples were assayed for concentration of LH and FSH. Progesterone concentrations were determined in samples collected on d 4, 6 and 10 after ovulation. Number and size of follicles and detection of ovulation were determined by ultrasonography. Number of mares induced to ovulate within 30 d was 0 of 15, 7 of 15 and 9 of 15 for groups 1, 2 and 3, respectively. During treatment, follicle sizes were smaller for mares in group 3 (implant). The LH response to GnRH agonist (area under curve) was similar among groups at d 0 but was greater (P less than .05) for mares in group 3 on d 7 and 14 and groups 2 and 3 on d 21 than for controls. A similar pattern was detected for peak concentrations of LH after GnRH on d 0, 7, 14 and 21. Daily concentrations of LH remained low in untreated control mares compared with GnRH-treated mares throughout the sampling period. Concentrations of LH for mares in group 3 that ovulated were elevated greatly above those for group 2 mares, whereas concentrations of FSH were similar in both treatment groups prior to ovulation. PMID- 2108109 TI - Growth of Listeria monocytogenes at refrigeration temperatures. AB - The growth of three strains of Listeria monocytogenes at refrigeration temperatures (-0.5 to 9.3 degrees C) in chicken broth and/or UHT milk was determined using a rocking temperature gradient incubator. Minimum growth temperatures ranged from -0.1 to -0.4 degree C for the three strains. Lag times of 1-3 d and 3 to greater than 34 d were observed with incubation at 5 and 0 degrees C respectively. Corresponding generation times ranged from 13-24 h at 5 degrees C and 62-131 h at 0 degree C. The type of culture medium had an influence on both the rate and extent of growth. Incubation of cultures at 4 degrees C before inoculation caused a marked reduction in the lag time when compared with cultures which had been previously incubated at 30 degrees C. PMID- 2108110 TI - Survival strategy of Escherichia coli and Enterococcus faecalis in illuminated fresh and marine systems. AB - Some effects of visible light on Escherichia coli and Enterococcus faecalis in natural freshwater and seawater were studied by plate counts, colony area measurements, and direct counts. A large number of somnicells (non-culturable cells) were noted in illuminated systems as compared with non-illuminated ones. Colony areas were significantly smaller in illuminated systems. Indirect activity measurements were used to test the effects of visible light on the ability of E. coli and Ent. faecalis to metabolize substrates ([14C]glucose) in natural waters. In illuminated systems, a decrease of glucose uptake was observed. When percentages of assimilation and respiration with respect to the total glucose uptake were analysed a decrease of assimilation percentages and an increase of respiration percentages were observed. In addition, differences in glucose uptake, assimilation and respiration by enteric bacteria were detected for E. coli at the beginning of the experiments between fresh- and seawater and these were interpreted as a toxic effect exerted by seawater on E. coli cells. Differences between species, natural waters and parameters studied (excepting glucose assimilation) were detected in the illuminated systems. We concluded, however, that enteric bacteria under visible light illumination show a general survival strategy characterized by reaching progressively a somnicell stage which can be defined in terms of their (1) inability to form colonies on standard bacteriological media, (2) inability to incorporate substrates, and (3) inactivation of biosynthetic processes. PMID- 2108111 TI - Treatment of Branhamella catarrhalis infections. PMID- 2108112 TI - Treatment of experimental listeriosis by CI 934, a new quinolone. AB - CI 934, a new quinolone, is only marginally more active in vitro against Listeria monocytogenes and other Listeria spp. than ciprofloxacin. A bactericidal effect is seen only after several hours of incubation. However, mice infected with a virulent strain of L. monocytogenes were protected by parenteral treatment with CI 934. With a dosage of 2 x 2 mg CI 934 per day for three days almost complete remission could be achieved. These results are somewhat better than those obtained in previous experiments with other antibiotics. PMID- 2108113 TI - Does administration of an aminoglycoside in a single daily dose affect its efficacy and toxicity? AB - Treatment efficacy, oto- and nephrotoxicity, and aminoglycoside pharmacokinetics were evaluated in a prospective, comparative, randomized clinical study of aminoglycosides given once a day or three times a day for severe infections. Sixty patients were treated with netilmicin or gentamicin 4.5 mg/kg bodyweight/day, either once a day or divided into three doses a day. The patients were allocated randomly to the different groups. The clinical effect was difficult to compare in the different groups, because of the small numbers of patients. Therapeutic failures were seen in seven patients (three after one and four after three doses per day). Two patients, one with Staphylococcus aureus endocarditis and one with streptococcal endocarditis, on netilmicin once daily and conventional high-dose therapy with a penicillin had positive blood cultures after five and seven days of treatment, respectively. Vestibular function and hearing acuity were examined by serial audiograms and electronystagmograms. In spite of extensive diagnostic evaluation, only two cases of ototoxicity were detected. One patient treated with gentamicin three times a day developed vertigo and a severe abnormality of her electronystagmogram. One young patient treated with gentamicin once daily had a slight bilateral reduction of hearing. Nephrotoxicity was mild and did not differ in the four treatment groups. This was the first investigation of a once-daily dosing regimen conducted in seriously ill patients with systemic infections. We could not demonstrate any evidence that aminoglycoside treatment once daily has greater oto- or nephrotoxicity than the traditional three times daily regimen. PMID- 2108114 TI - The effect of mafenide on dihydropteroate synthase. AB - Using intact bacterial cells, it was found that Pseudomonas aeruginosa was more susceptible to mafenide than Escherichia coli, that p-aminobenzoic acid (pABA) did not reverse or prevent inhibition by mafenide and that pABA itself was inhibitory. Under the experimental conditions used in these studies, pABA was more inhibitory to E. coli than to P. aeruginosa. It is proposed that pABA could be of use in the topical treatment of burn wounds. At the enzyme level, it was shown that mafenide did not inhibit dihydropteroate synthase. Thus, mafenide appeared not to exert its inhibitory effects in the same manner as the structurally related sulphonamides. PMID- 2108115 TI - Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate. AB - A Pseudomonas aeruginosa (isolate 416) from a patient with pneumonia, was initially susceptible to imipenem (MIC: 2 mg/l) but became resistant to this antibiotic (isolate 470, MIC: 32 mg/l) during imipenem therapy. Treatment failed. No parallel increases in MIC were observed for other antimicrobials tested. Isolates 416 and 470 shared the same pyocin type and serotype, produced small amounts of an inducible beta-lactamase, and had similar lipopolysaccharide compositions. On electrophoresis of outer membrane proteins, the porin F, identified by the monoclonal antibody MA4-4, was expressed similarly by the two isolates but the production of one band (apparent molecular weight: 47,000) was diminished in isolate 470. [14C]-Imipenem labelling of intact cells proceeded more slowly in 470 than in 416, especially when bacterial cells were treated by antibody MA4-4 to block the porin F channel. [14C]-Imipenem labelling of penicillin binding proteins (PBP) showed that the band identified as PBP-4 bound markedly less radioactivity in isolate 470 than in 416. After isolate 470 was passaged several times in antibiotic-free broth, the imipenem MIC was decreased from 32 to 8 mg/l, and the [14C]-imipenem PBP pattern recovered the initial profile as exhibited by isolate 416. Two resistance mechanisms, affecting imipenem electively, could have combined their effect in the post-therapy isolate, altered target protein and reduced permeability. PMID- 2108116 TI - Lomefloxacin-induced modification of the kinetics of growth of gram-negative bacteria and susceptibility to phagocytic killing by human neutrophils. AB - The post-antibiotic effect (PAE) of lomefloxacin against Escherichia coli and Pseudomonas aeruginosa was determined and compared with various other antibiotics. All the quinolones tested, and chloramphenicol and gentamicin, possessed PAE activity. At 10 x MIC and 30 min exposure, the PAEs against E. coli were 1.6, 1.3, and 1.8 h for lomefloxacin, ciprofloxacin and norfloxacin respectively, and for P. aeruginosa the equivalent PAEs were 1.1, 1 and 0.5 h. The lomefloxacin PAE was dose-dependent and exposure for 5 min was sufficient to give optimal PAE at high concentrations of lomefloxacin. Such brief exposure rapidly blocked bacterial nucleic acid biosynthesis. Lomefloxacin pretreated bacteria were more susceptible to killing by PMN than untreated bacteria. Optimum enhancement of phagocytic killing of E. coli occurred when exposure to lomefloxacin was associated with an 80% decrease in cfu during pretreatment. Maximum PMN activity against P. aeruginosa occurred when bacteria were exposed to lomefloxacin producing change in cfu of +0.2 log10 to -0.7 log10. These results indicate that phenotypic changes of P. aeruginosa and E. coli exposed to lomefloxacin render the bacteria more susceptible to phagocytic killing. PMID- 2108117 TI - Fetal breathing, sleep state, and cardiovascular responses to adenosine in sheep. AB - The possibility that adenosine mediates hypoxic inhibition of fetal breathing and eye movements was tested in nine chronically catheterized fetal sheep (0.8 term). Intracarotid infusion of adenosine (0.25 +/- 0.03 mg.min-1.kg-1) for 1 h to the fetus increased heart rate and hemoglobin concentration but did not significantly affect mean arterial pressure or blood gases. As with hypoxia, adenosine decreased the incidence of rapid eye movements by 55% and the incidence of breathing by 77% without significantly affecting the incidence of low-voltage electrocortical activity. However, with longer (9 h) administration, the incidence of breathing and eye movements returned to normal during the adenosine infusion. Intravenous infusion of theophylline, an adenosine receptor antagonist, prevented most of the reduction in the incidence of breathing and eye movements normally seen during severe hypoxia (delta arterial PO2 = -10 Torr). It is concluded that 1) adenosine likely depresses fetal breathing and eye movements during hypoxia and 2) downregulation of adenosine receptors may contribute to the adaptation of breathing and eye movements during prolonged hypoxia. PMID- 2108118 TI - Hypocapnia does not alter collateral ventilation in sheep. AB - Hypocapnic constriction has been proposed as a mechanism by which collateral pathways might rapidly alter ventilation to match perfusion. We studied the changes in response to hypocapnia with age in sheep, a species with collateral resistance (Rcoll) similar to those measured in humans. Measurements of Rcoll were made with either 5 or 10% CO2 and with air (hypocapnia) in 29 anesthetized sheep, ages 6 mo to 10 yr, with the wedged bronchoscope technique. Rcoll was 0.42 +/- 0.12, 0.58 +/- 0.18, 0.32 +/- 0.18, and 0.17 +/- 0.04 (SE) cmH2O.ml-1.min in 6-mo- and 1-, 2-, and 10-yr-old animals, respectively. These values were unchanged with hypocapnia. Despite the lack of a change in Rcoll with hypocapnia, administration of histamine aerosol (8 animals) through the bronchoscope increased Rcoll by 151 +/- 35% (P less than 0.05). These data suggest that although collateral pathways exist in sheep and are capable of constriction, they do not respond to hypocapnia. Furthermore, the response to hypocapnia is not influenced by age. PMID- 2108119 TI - Differences in insulin-induced glucose uptake and enzyme activity in running rats. AB - To evaluate the relationship between enhanced insulin action and level of exercise training, in vivo glucose uptake was assessed in the absence of added insulin and during insulin-stimulated conditions for three activity levels of voluntarily trained rats (low 2-5 km/day, medium 6-9 km/day, high 11-16 km/day). After rats rested for 24 h and fasted overnight, glucose uptake was estimated by comparing steady-state serum glucose (SSSG) levels at low insulin (SSSI) concentrations achieved during an insulin suppression test. In the absence of added insulin, SSSI averaged approximately 20 microU/ml and glucose uptake was similar for high runners and younger weight-matched controls. However, with insulin added to sustain SSSI at approximately 35 microU/ml, SSSG was significantly reduced in all runners (P less than 0.02), with the lowest value attained in high runners. Fasting serum triglycerides were also reduced in all runners (P less than 0.05), with the lowest values seen in medium and high runners. The concentration of glycogen in liver and select skeletal muscles at the start of the study was not different between trained and control rats, suggesting that enhanced insulin-stimulated glucose uptake was not the result of lower glycogen levels. In addition, glycogen synthase and succinate dehydrogenase activities in biceps femoris muscle were only elevated for high runners, but glycogen synthase activity was not enhanced in plantaris muscle and was decreased in soleus muscle. These findings indicate that enhanced insulin-stimulated glucose uptake and reduced serum triglyceride concentrations induced in exercise trained rats at varying activity levels are dissociated from changes in glycogen synthase and oxidative enzyme activity for skeletal muscle. PMID- 2108120 TI - Oxygen radicals in capsaicin-induced bronchoconstriction. AB - The role of oxygen radicals in capsaicin-induced bronchoconstriction was investigated using scavengers of the radicals. A total of 48 guinea pigs weighing 293 +/- 7 g were employed in this study, which consisted of two phases. In phase 1, 35 anesthetized paralyzed animals were divided into five groups: group 1A, control (n = 6); group 1B, chronic dimethylthiourea (DMTU, n = 12); group 1C, acute DMTU (n = 6); group 1D, superoxide dismutase (n = 4); and group 1E, catalase (n = 7). All animals were injected with capsaicin (16 micrograms/kg iv), and changes in respiratory compliance and maximal expiratory flow rate were used as indicators of bronchoconstriction. The capsaicin injection caused a marked airway spasm that was significantly ameliorated by chronic DMTU pretreatment, but no amelioration was noted with the other treatments. An additional study for group 1C was performed using a double dose of DMTU. Again no amelioration was found. In phase 2, 13 animals were divided into two groups: group 2A, substance P (SP, n = 7) and group 2B, chronic DMTU + SP (n = 6). There was no significant difference in SP-induced bronchoconstriction between animals in these two groups. These data suggest that capsaicin-induced airway constriction is modulated by oxygen radicals which may augment mainly on the biosynthesis and/or axonal transport of tachykinins. PMID- 2108121 TI - Effects of ischemic and hypoxic hypoxia on VO2 and lactic acid output during tetanic contractions. AB - We measured O2 uptake (VO2), CO2 output (VCO2), and net lactic acid output (L) during a 30-min period of repetitive 1/s isotonic tetanic contractions of the dog gastrocnemius-plantaris muscle group. The conditions were modest ischemic hypoxia (ischemia), hypoxia hypoxia (hypoxia), and free-flow normoxia (control). The major goal was to assess the effects of these perturbations on L during contractions. Ischemia and hypoxia were initiated just before the start of the contractions and at minute 7 of contractions in separate groups of experiments. Whenever applied, both ischemia and hypoxia reduced VO2 compared with the control values. When ischemia was initiated at the start of contractions, L was reduced transiently compared with the controls. When ischemia began at minute 7, L was increased modestly but transiently compared with the controls. When hypoxia was initiated at the start of contractions, L was increased during the entire period of contractions. The L pattern was the same as in the controls, rising to a maximal value at 3 min and declining steadily to a lower value at 30 min. When hypoxia began at minute 7, L declined initially at a slower rate than it did in the controls and was thereby elevated above the controls from 9 to 30 min. Ischemia was associated with a more rapid reduction in mechanical performance than hypoxia. The data suggest that the mechanisms of the decreased mechanical performance and VO2 are different for ischemia and hypoxia. PMID- 2108122 TI - Fish cell lines: establishment and characterization of three new cell lines from grass carp (Ctenopharyngodon idella). AB - Three new cell lines were established from tissues of the grass carp, Ctenopharyngodon idella. Derived from the fin, snout, and swim bladder of two apparently healthy diploid fry, these cell lines have been designated GCF, GCS-2, and GCSB, respectively. The cells grew at temperatures between 24 degrees and 36 degrees C with optimal growth at 32 degrees C and have been subcultured more than 50 times since their initiation in August 1986. Two of the lines remained diploid or pseudodiploid after 38 passages. The cells were tested for microbial contamination, and plating efficiencies were determined. The three cell lines were sensitive to Rhabdovirus carpio (RVC), infectious hematopoietic necrosis virus (IHNV), golden shiner virus (GSV), chum salmon virus (CSV), and infectious pancreatic necrosis virus serotype VR299 IPNV). They were refractory to channel catfish virus (CCV), channel catfish reovirus (CRV), chinook salmon paramyxovirus (CSP), and an Ab serotype of IPNV. PMID- 2108123 TI - Roles of CfxA, CfxB, and external electron acceptors in regulation of ribulose 1,5-bisphosphate carboxylase/oxygenase expression in Rhodobacter sphaeroides. AB - The Rhodobacter sphaeroides genome contains two unlinked genetic regions each encoding a series of proteins involved in CO2 fixation which include phosphoribulokinase (prkA and prkB) and ribulose 1,5-bisphosphate carboxylase/oxygenase (rbcLS and rbcR) (P. L. Hallenbeck and S. Kaplan, Photosynth. Res. 19:63-71, 1988; F. R. Tabita, Microbiol. Rev. 52:155-189, 1988). We examined the effect of CO2 in the presence and absence of an alternate electron acceptor, dimethyl sulfoxide, on the expression of rbcR and rbcLS in photoheterotrophically grown R. sphaeroides. The expression of both rbcR and rbcLS was shown to depend on the CO2 concentration when succinate was used as the carbon source. It was also demonstrated that CO2 fixation is critical for photoheterotrophic growth but could be replaced by the alternative reduction of dimethyl sulfoxide to dimethyl sulfide. Dimethyl sulfoxide severely depressed both rbcR and rbcLS expression in cells grown photoheterotrophically at CO2 concentrations of 0.05% or greater. However, cells grown photoheterotrophically in the absence of exogenous CO2 but in the presence of dimethyl sulfoxide had intermediate levels of expression of rbcL and rbcR, suggesting partially independent control by limiting CO2 tension. We also present evidence for the existence of two gene products, namely, CfxA and CfxB, which are encoded by genes immediately upstream of rbcLS and rbcR, respectively. Strains were constructed which contained null mutations in cfxA and/or cfxB. Each mutation eliminated expression of the linked downstream rbc operon. Further, studies utilizing these strains demonstrated that each form of ribulose 1,5-bisphosphate carboxylase/oxygenase plays an essential role in maintaining the cellular redox balance during photoheterotrophic growth at differing CO2 concentrations. PMID- 2108124 TI - A novel Bacillus subtilis gene involved in negative control of sporulation and degradative-enzyme production. AB - We have cloned a 2.5-kilobase fragment of the Bacillus subtilis genomic DNA which caused the reduction of extracellular and cell-associated protease levels when present in high copy number. This fragment, in multicopy, was also responsible for reduced levels of alpha-amylase, levansucrase, alkaline phosphatase, and sporulation inhibition. The gene relevant to this pleiotropic phenotype is referred to as pai. By DNA sequencing, two open reading frames--ORF1 and ORF2, encoding polypeptides of 172 and 207 amino acid residues, respectively--were found. These open reading frames seemed to form an operon. Deletion analysis revealed that an entire region for ORF1 and ORF2 was necessary for the pai phenotype. In addition, it was observed that the presence of the pai gene, in multicopy, caused overproduction of two proteins (molecular masses, 21 and 24 kilodaltons [kDa]). Analyses of the N-terminal amino acid sequences of these two proteins suggested that they were products of ORF1 and ORF2. Disruption of the pai gene at ORF1 in the genomic DNA resulted in the release of repression on protease synthesis and sporulation in glucose-enriched (2%) medium. The mutant carrying insertional disruption at ORF2 could not be constructed, suggesting that the ORF2 product, the 24-kDa protein, is essential for growth. The 21-kDa protein contains a helix-turn-helix domain observed in other DNA-binding proteins. Chromosomal mapping of pai indicated that this gene is located close to thr-5. These results suggest that the pai gene is a novel transcriptional-regulation gene involved in glucose repression. PMID- 2108125 TI - Transcriptional organization of a cloned chemotaxis locus of Bacillus subtilis. AB - A cloned chemotaxis operon has been characterized. Thirteen representative che mutations from different complementation groups were localized on the physical map by recombination experiments. The use of integration plasmids established that at least 10 of these complementation groups within this locus are cotranscribed. An additional three complementation groups may form part of the same transcript. The direction of transcription and the time of expression were determined from chromosomal che-lacZ gene fusions. The promoter was cloned and localized to a 3-kilobase fragment. Expression of beta-galactosidase from this promoter was observed primarily during the logarithmic phase of growth. Three factor PBS1 cotransduction experiments were performed to order the che locus with respect to adjacent markers. The cheF141 mutation is 70 to 80% linked to pyrD1. This linkage is different from that reported previously (G. W. Ordal, D. O. Nettleton, and J. A. Hoch, J. Bacteriol. 154:1088-1097, 1983). The cheM127 mutation is 57% linked by transformation to spcB3. The gene order determined from all crosses is pyrD-cheF-cheM-spcB. PMID- 2108126 TI - Chromosomal transformation in the cyanobacterium Agmenellum quadruplicatum. AB - Chromosomal transformation of Agmenellum quadruplicatum PR-6 (= Synechococcus sp. strain 7002) was characterized for phenotypic expression, for exposure time to DNA, and for dependence on DNA concentration with regard to Rifr donor DNA. Exponentially growing cells of PR-6 were competent for chromosomal transformation. Competence decreased in cells in the stationary phase of growth or in cells deprived of a nitrogen source. Dark incubation of cells before exposure to donor DNA also decreased competence. Homologous Rifr and Strr DNA and heterologous Escherichia coli W3110 DNA were used in DNA-DNA competition studies, which clearly showed that DNA binding by PR-6 was nonspecific. DNA binding and uptake by PR-6 exhibited single-hit kinetics. Single-stranded DNA failed to transform competent cells of PR-6, and DNA eclipse was not observed, suggesting that double-stranded DNA was the substrate for the binding and uptake reactions during the transformation of PR-6. A significant improvement in transformation frequency was achieved by increasing the nitrate content of the culture medium and by lowering the temperature at which cells were exposed to donor DNA from 39 degrees C (the optimal temperature for growth) to 30 degrees C. PMID- 2108127 TI - Complex character of senS, a novel gene regulating expression of extracellular protein genes of Bacillus subtilis. AB - The senS gene of Bacillus subtilis, which in high copy number stimulates the expression of several extracellular-protein genes, has been cloned, genetically mapped, and sequenced. The gene codes for a highly charged basic protein containing 65 amino acid residues. The gene is characterized by the presence of a transcription terminator (attenuator) located between the promoter and open reading frame, a strong ribosome-binding site, and a strong transcription terminator at the 3' end of this monocistronic gene. The amino acid sequence of SenS showed partial homology with the N-terminal core binding domain region of bacterial RNA polymerase sigma factors and a helix-turn-helix motif found in DNA binding proteins. The gene can be deleted without any effect on growth or sporulation. PMID- 2108128 TI - Bacteriophage-enhanced sporulation: comparison of spore-converting bacteriophages PMB12 and SP10. AB - The previously characterized bacteriophage SP10 enhanced the frequency of wild type sporulation by Bacillus subtilis W23 and 3-13. Comparison of SP10 with the spore-converting bacteriophage PMB12 indicated that both bacteriophages significantly increased the sporulation frequency of an oligosporogenic mutant that contained spo0J::Tn917 omega HU261. SP10 and PMB12 caused wild-type bacteria to sporulate in a liquid medium that initially contained enough glucose to inhibit the sporulation and expression of alpha-amylase by uninfected bacteria. SP10 also induced the expression of alpha-amylase in the presence of glucose, whereas PMB12 had no detectable effect. These observations were consistent with the conclusion that SP10 is a spore-converting bacteriophage and that SP10 and PMB12 relieve glucose-mediated catabolite repression of sporulation by different mechanisms. PMID- 2108129 TI - Different and rapid responses of four cyanobacterial psbA transcripts to changes in light intensity. AB - The genome of the cyanobacterium Synechococcus sp. strain PCC 7942 contains three psbA genes which encode two forms of the D1 protein of photosystem II. Experiments using psbA-lacZ translational fusions and Western blot (immunoblot) analysis have shown that the psbA genes respond differently to changes in light intensity, altering the ratio of the two forms of D1 in the thylakoid membrane. Each gene produces a 1.2-kilobase (kb) mRNA. A probe specific for psbAII transcripts also identified a 1.6-kb mRNA which starts 419 base pairs upstream of the 5' end of the 1.2-kb species and overlaps the entire 1.2-kb transcript. This 419-base-pair region includes an open reading frame (ORF1) of 114 amino acids. We investigated the effects of changes in light intensity on psbAII transcript levels in a series of light shift experiments in the wild-type Synechococcus sp. and in AMC084, a mutant which does not produce the 1.6-kb transcript. After exposure to high light intensities for 15 min, the level of the 1.2-kb psbAII transcript increased in both strains. This transcript was not detected in either strain after transfer to low light intensity. The psbAIII transcript showed the same pattern of response as the 1.2-kb psbAII transcript, whereas the 1.6-kb psbAII transcript was unaffected by different light intensities. The psbAI transcript levels responded oppositely to those of psbAII and psbAIII. These data, considered along with previous results obtained by using lacZ translational gene fusions, indicate that the response of psbA genes to changes in light intensity is controlled primarily at the transcriptional level. PMID- 2108130 TI - Catabolic thiosulfate disproportionation and carbon dioxide reduction in strain DCB-1, a reductively dechlorinating anaerobe. AB - Strain DCB-1 is a strict anaerobe capable of reductive dehalogenation. We elucidated metabolic processes in DCB-1 which may be related to dehalogenation and which further characterize the organism physiologically. Sulfoxy anions and CO2 were used by DCB-1 as catabolic electron acceptors. With suitable electron donors, sulfate and thiosulfate were reduced to sulfide. Sulfate and thiosulfate supported growth with formate or hydrogen as the electron donor and thus are probably respiratory electron acceptors. Other electron donors supporting growth with sulfate were CO, lactate, pyruvate, butyrate, and 3-methoxybenzoate. Thiosulfate also supported growth without an additional electron donor, being disproportionated to sulfide and sulfate. In the absence of other electron acceptors, CO2 reduction to acetate plus cell material was coupled to pyruvate oxidation to acetate plus CO2. Pyruvate could not be fermented without an electron acceptor. Carbon monoxide dehydrogenase activity was found in whole cells, indicating that CO2 reduction probably occurred via the acetyl coenzyme A pathway. Autotrophic growth occurred on H2 plus thiosulfate or sulfate. Diazotrophic growth occurred, and whole cells had nitrogenase activity. On the basis of these physiological characteristics, DCB-1 is a thiosulfate disproportionating bacterium unlike those previously described. PMID- 2108131 TI - Evaluation of freeze-substitution and conventional embedding protocols for routine electron microscopic processing of eubacteria. AB - Freeze-substitution and more conventional embedding protocols were evaluated for their accurate preservation of eubacterial ultrastructure. Radioisotopes were specifically incorporated into the RNA, DNA, peptidoglycan, and lipopolysaccharide of two isogenic derivatives of Escherichia coli K-12 as representative gram-negative eubacteria and into the RNA and peptidoglycan of Bacillus subtilis strains 168 and W23 as representative gram-positive eubacteria. Radiolabeled bacteria were processed for electron microscopy by conventional methods with glutaraldehyde fixation, osmium tetroxide postfixation, dehydration in either a graded acetone or ethanol series, and infiltration in either Spurr or Epon 812 resin. A second set of cells were simultaneously freeze-substituted by plunge-freezing in liquid propane, substituting in anhydrous acetone containing 2% (wt/vol) osmium tetroxide, and 2% (wt/vol) uranyl acetate, and infiltrating in Epon 812. Extraction of radiolabeled cell components was monitored by liquid scintillation counting at all stages of processing to indicate retention of cell labels. Electron microscopy was also used to visually confirm ultrastructural integrity. Radiolabeled nucleic acid and wall components were extracted by both methods. In conventionally embedded specimens, dehydration was particularly damaging, with ethanol-dehydrated cells losing significantly more radiolabeled material during dehydration and subsequent infiltration than acetone-treated cells. For freeze-substituted specimens, postsubstitution washes in acetone were the most deleterious step for gram-negative cells, while infiltration was more damaging for gram-positive cells. Autoradiographs of specimens collected during freeze-substitution were scanned with an optical densitometer to provide an indication of freezing damage; the majority of label lost from freeze-substituted cells was a result of poor freezing to approximately one-half of the cell population, thus accounting for the relatively high levels of radiolabel detected in the processing fluids. These experiments revealed that gram-positive and gram negative cells respond differently to freezing; these differences are discussed with reference to wall structure. It was apparent that the cells frozen first (ie., the first to contact the cryogen) retained the highest percentage of all radioisotopes, and the highest level of cellular infrastructure, indicative of better preservation. The preservation of these select cells was far superior to that obtained by more conventional techniques. PMID- 2108132 TI - Effect of chemical fixatives on accurate preservation of Escherichia coli and Bacillus subtilis structure in cells prepared by freeze-substitution. AB - Five chemical fixatives were evaluated for their ability to accurately preserve bacterial ultrastructure during freeze-substitution of select Escherichia coli and Bacillus subtilis strains. Radioisotopes were specifically incorporated into the peptidoglycan, lipopolysaccharide, and nucleic acids of E. coli SFK11 and W7 and into the peptidoglycan and RNA of B. subtilis 168 and W23. The ease of extraction of radiolabels, as assessed by liquid scintillation counting during all stages of processing for freeze-substitution, was used as an indicator of cell structural integrity and retention of cellular chemical composition. Subsequent visual examination by electron microscopy was used to confirm ultrastructural conformation. The fixatives used were: 2% (wt/vol) osmium tetroxide and 2% (wt/vol) uranyl acetate; 2% (vol/vol) glutaraldehyde and 2% (wt/vol) uranyl acetate; 2% (vol/vol) acrolein and 2% (wt/vol) uranyl acetate; 2% (wt/vol) gallic acid; and 2% (wt/vol) uranyl acetate. All fixatives were prepared in a substitution solvent of anhydrous acetone. Extraction of cellular constituents depended on the chemical fixative used. A combination of 2% osmium tetroxide-2% uranyl acetate or 2% gallic acid alone resulted in optimum fixation as ascertained by least extraction of radiolabels. In both gram-positive and gram negative organisms, high levels of radiolabel were detected in the processing fluids in which 2% acrolein-2% uranyl acetate, 2% glutaraldehyde-2% uranyl acetate, or 2% uranyl acetate alone were used as fixatives. Ultrastructural variations were observed in cells freeze-substituted in the presence of different chemical fixatives. We recommend the use of osmium tetroxide and uranyl acetate in acetone for routine freeze-substitution of eubacteria, while gallic acid is recommended for use when microanalytical processing necessitates the omission of osmium. PMID- 2108133 TI - A mutation in P23, the first gene in the RNA polymerase sigma A (sigma 43) operon, affects sporulation in Bacillus subtilis. AB - Mutations within P23, the first gene of the Bacillus subtilis sigma A operon, were not detrimental to vegetative growth or sporulation. One deletion of P23 resulted in a strain that sporulated earlier than the wild type. This aberrant phenotype may be due to the simultaneous deletion of a sigma H promoter from the sigma A operon. PMID- 2108134 TI - Alkaline induction of a novel gene locus, alx, in Escherichia coli. AB - A novel pH-regulated locus inducible over 100-fold in alkaline media was identified in Escherichia coli through screening of 93,000 Mu dI1734 (lacZ Kmr) operon fusions at pH 6.5 and pH 8.5. Four lacZ fusions that showed expression only at the higher pH were mapped at 67.5 min by P1 transduction crosses. The locus was designated alx. PMID- 2108135 TI - A new type of exo-beta-glucuronidase acting only on non-sulfated glycosaminoglycans. AB - Using chondroitin as a substrate, a new type of exo-beta-glucuronidase (EC 3.2.1.31) from rabbit liver was purified using a combination of ammonium sulfate fractionation, DEAE-cellulose chromatography, gel filtration on Sephracryl S-300, affinity chromatography through heparin-Sepharose CL-6B, and preparative polyacrylamide gel electrophoresis. This enzyme acts only on non-sulfated glycosaminoglycans and their oligosaccharides and was shown to be quite different from exo-beta-glucuronidase, which does act on p-nitro-phenyl-beta-D-glucuronide with regard to the following properties. 1) Neither sulfated glycosaminoglycanoligosaccharides nor p-nitrophenyl-beta-D-glucuronide were substrates for the enzyme. 2) The molecular weight was found to be about 130,000 by gel filtration, compared with a molecular weight of 280,000-300,000 for beta glucuronidase, which acts on p-nitro-phenyl-beta-D-glucuronide. 3) The enzyme showed maximal activity at pH 5.0, compared with an optimum pH of 4.5 for beta glucuronidase, which acts on p-nitro-phenyl-beta-D-glucuronide. 4) The enzyme showed maximal activity in 0.075 M NaCl but no activity above 0.25 M NaCl. 5) The enzyme was inhibited strongly by compounds bearing a sulfate group. 6) The enzyme did not react with an antibody against beta-glucuronidase acting on p-nitrophenyl D-glucuronide. It is suggested that the enzyme may be involved in the catabolism of glycosaminoglycans, acting especially on chondroitin after the desulfation reaction and/or hyaluronic acid, but showing little involvement with the detoxification system. PMID- 2108136 TI - Hormone-dependent phosphorylation of the glucocorticoid receptor occurs mainly in the amino-terminal transactivation domain. AB - Phosphorylation of glucocorticoid receptors is increased by hormone binding and has been implicated in transcriptional regulation. We performed a phosphoamino acid analysis and identified the phosphorylated regions of the glucocorticoid receptor with respect to its functional domains before and after hormone activation. Receptor was isolated by immunoprecipitation from [32P]orthophosphate labeled FTO 2B rat hepatoma cells grown in the absence or presence of glucocorticoids. The receptor contained mainly phosphoserine, with little phosphothreonine and no phosphotyrosine. Partial proteolysis of receptor from hormone-treated or control cells revealed a similar phosphopeptide pattern. Chemical cleavage with hydroxylamine and cyanogen bromide or digestion with trypsin and chymotrypsin localized the majority of receptor phosphorylation sites to a transactivation domain amino-terminal of the DNA-binding domain. Phosphorylation of this region, termed tau 1/enh2, was increased 2-3-fold by hormone treatment. The DNA-binding domain itself is weakly phosphorylated; no phosphorylation was found in the hormone-binding domain. Phosphorylated regions were also identified in receptor deletion mutants stably transfected into CV-1 monkey kidney cells. Hormone-independent phosphorylation was observed with a strong constitutively active mutant lacking the hormone-binding domain. No phosphorylation was detected in a mutant lacking the amino-terminal region, which showed only weak, hormone-dependent activity. These results support the idea that phosphorylation is important for the strength of the glucocorticoid receptor as a transcriptional regulator. PMID- 2108137 TI - A calcium-dependent mechanism for associating a soluble arachidonoyl-hydrolyzing phospholipase A2 with membrane in the macrophage cell line RAW 264.7. AB - Arachidonoyl-hydrolyzing phospholipase A2 plays a central role in providing substrate for the synthesis of the potent lipid mediators of inflammation, the eicosanoids, and platelet-activating factor. Although Ca2+ is required for arachidonic acid release in vivo and most phospholipase A2 enzymes require Ca2+ for activity in vitro, the role of Ca2+ in phospholipase A2 activation is not understood. We have found that an arachidonoyl-hydrolyzing phospholipase A2 from the macrophage-like cell line, RAW 264.7, exhibits Ca2(+)-dependent association with membrane. The intracellular distribution of the enzyme was studied as a function of the Ca2+ concentration present in homogenization buffer. The enzyme was found almost completely in the 100,000 x g soluble fraction when cells were homogenized in the presence of Ca2+ chelators and there was a slight decrease in soluble fraction activity when cells were homogenized at the level of Ca2+ in an unstimulated cell (80 nM). When cells were homogenized at Ca2+ concentrations expected in stimulated cells (230-450 nM), 60-70% of the phospholipase A2 activity was lost from the soluble fraction and became associated with the particulate fraction in a manner that was partly reversible with EGTA. Membrane associated phospholipase A2 activity was demonstrated by [3H]arachidonic acid release both from exogenous liposomes and from radiolabeled membranes. With radiolabeled particulate fraction as substrate, this enzyme hydrolyzed arachidonic acid but not oleic acid from membrane phospholipid, and [3H]arachidonic acid was derived from phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol/phosphatidylserine. We suggest a mechanism in which the activity of phospholipase A2 is regulated by Ca2+: in an unstimulated cell phospholipase A2 is found in the cytosol; upon receptor ligation the cytosolic Ca2+ concentration increases, and the enzyme becomes membrane-associated which facilitates arachidonic acid hydrolysis. PMID- 2108138 TI - Spinach carbonic anhydrase primary structure deduced from the sequence of a cDNA clone. AB - A cDNA clone 1,156 base pairs in length was selected by screening a lambda gt11 library with antibodies directed against spinach chloroplast carbonic anhydrase (carbonate dehydratase, EC 4.2.1.1). Sequence analysis revealed an open reading frame of 957 base pairs encoding a polypeptide containing 319 amino acids with a molecular weight of 34,569. This polypeptide is of sufficient size to represent the precursor of spinach chloroplast carbonic anhydrase. The polypeptide contains a sequence of 19 amino acids identical to the sequence of a cyanogen bromide fragment from spinach carbonic anhydrase. In addition, Escherichia coli was transformed with a plasmid that expresses spinach carbonic anhydrase. Lysates prepared from transformed E. coli contain acetazolamide-inhibitable carbonic anhydrase activity. The amino acid sequence of spinach carbonic anhydrase is distinct from those reported for the mammalian isozymes. PMID- 2108139 TI - A critical arginine in the large subunit of ribulose bisphosphate carboxylase/oxygenase identified by site-directed mutagenesis. AB - Rapid inactivation by phenylglyoxal of ribulose bisphosphate carboxylase/oxygenase (ribulose-P2 carboxylase) from the cyanobacterium Anacystis nidulans suggests the presence of an essential arginine, the modification of which is reduced in the presence of the substrate ribulose bisphosphate. Arginine 292 in the large subunit of ribulose-P2 carboxylase from A. nidulans was chosen for site-directed mutagenesis studies on the basis of the complete conservation of this residue in corresponding sequences of ribulose-P2 carboxylase from divergent organisms. Arginine 292 was changed to leucine and to lysine by directed mutagenesis using suitable plasmids and the bacteriophage M13. Both substitutions resulted in the production of purifiable holoenzyme with no activity after expression in Escherichia coli. PMID- 2108140 TI - 1H NMR spectrum of the native human insulin monomer. Evidence for conformational differences between the monomer and aggregated forms. AB - The effects of high dilution on the 1H Fourier transform NMR spectrum of native human insulin at pH* 8.0 and 9.3 have been examined at 500 MHz resolution. The dependence of the spectrum on concentration and comparison with the spectrum of a biologically highly potent monomeric insulin mutant (SerB9----Asp) establish that at 36 microM (pH* 9.3) or 18 microM (pH* 8) and no added buffer or salts, human insulin is monomeric. Under these conditions of dilution, ionic strength, and pH*, human insulin and the SerB9----Asp mutant exhibit nearly identical 1H NMR spectra. At higher concentrations (i.e. greater than 36 microM to 0.91 mM), native human insulin dimerizes, and this aggregation causes a change in insulin conformation. Although there are many changes in the spectrum, the TyrB26 ring H3,5 proton signals located at 6.63 ppm and the methyl signal located at 0.105 ppm (characteristics of monomeric insulin) are particularly distinct signatures of the conformation change that accompanies dimerization. Magnetization transfer experiments show that the 0.105 ppm methyl signal shifts downfield to a new position at 0.45 ppm. We conclude that the 0.105 ppm methyl signal is due to a conformation in which a Leu methyl group is centered over and in van der Waals contact with the ring of an aromatic side chain. Dimerization causes a conformation change that alters this interaction, thereby causing the downfield shift. Nuclear Overhauser studies indicate that the methyl group involved is located within a cluster of aromatic side chains and that the closest ring-methyl group interaction is with the ring of PheB24. PMID- 2108141 TI - Thermodynamic properties of the binding of alpha-, omega-amino acids to the isolated kringle 4 region of human plasminogen as determined by high sensitivity titration calorimetry. AB - The binding of alpha-, omega-amino acids, which are important effectors of human plasminogen activation, to the isolated kringle 4 (K4) peptide region of this protein has been investigated by high sensitivity titration calorimetry. The titration curve of the heat changes accompanying binding of the widely employed ligand, epsilon-aminocaproic acid (EACA), to K4 were deconvoluted to yield the following binding characteristics: n = 0.87 +/- 0.08 mol/mol; Ka = 3.82 +/- 0.37 x 10(4) M-1; delta H = -4.50 +/- 0.22 kcal/mol; delta S = 6.01 +/- 0.7 entropy units; and delta G = 6.29 +/- 0.06 kcal/mol. Here, both delta H and delta S provide the driving force of the interaction, with both hydrogen bonds and hydrophobic interactions, the latter which may result from an induced conformational change in K4 upon ligand binding, as well as possible alterations in peptide-bound water structure, providing the stabilizing forces for complex formation. The thermodynamic binding parameters were not greatly influenced by pH between the values of 5.5 and 8.2, suggesting that titratable groups on K4 in this pH region did not influence the binding. Investigations of the binding properties of structural analogues of EACA to K4 demonstrated that definable steric requirements existed for a maximal interaction, with spacing between the functional groups on EACA, as well as a hydrophobic region of this molecule, being important. This rapid and reliable method for measuring all thermodynamic parameters of formation of this complex at a given temperature can now be employed to investigate this important interaction with a wide variety of kringles and modified kringles to provide a more complete understanding of the necessary factors for this binding to occur. PMID- 2108142 TI - Purification of follitropin receptor from bovine calf testes. AB - Follitropin (FSH) receptors were solubilized from pure light membranes of bovine calf testis, using an optimum detergent to protein ratio of 0.01. The soluble FSH receptor fraction was gel filtered through Sepharose 6B to isolate an active fraction (6B-Fr-1) which behaved as a complex of FSH receptor and Gs protein. The 6B-Fr-1 was concentrated by ultrafiltration and further purified by sequential Sepharose 4B gel filtration, DEAE-cellulose chromatography (to separate the receptor from Gs protein), and wheat germ lectin affinity chromatography. The purified receptor had an FSH-binding capacity of approximately 3.47 nmol/mg of protein with a Kd of 1.9 X 10(-10) M. Yield was 526 micrograms/11.5 kg tested. Radioiodinated, as well as unlabeled purified FSH receptor, migrated on sodium dodecyl sulfate-polyacrylamide gels as a single major band of Mr approximately 240,000. This band was not affected by 8 M urea treatment prior to analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but treatment with dithiothreitol induced the loss of the 240-kDa band, with appearance of an Mr approximately 60,000 band. The availability of highly purified, stable FSH receptor should allow direct studies on its structure-function relationships. PMID- 2108143 TI - Site-directed mutagenesis in human tissue-plasminogen activator. Distinguishing sites in the amino-terminal region required for full fibrinolytic activity and rapid clearance from the circulation. AB - Recombinant variants of tissue plasminogen activator (t-PA) containing either substitutions or deletions of amino acids within the fibronectin finger-like domain (residues 6-50) were found to exhibit widely varying in vivo clearance profiles in rats and fibrinolytic activity in 125I-fibrin clot lysis assays. Clearance was not significantly affected by changes in the densely charged region of amino acid residues 7-10. Deletions or substitutions of amino acids in the region 14-32 decreased both fibrinolytic activity and the clearance of the enzyme. Modifications within the predicted omega loop of residues 37-41 affected clearance only to a small degree, whereas amino acid alterations in the region of residues 42-49 resulted in as much as a 6-fold decrease in the rate of clearance with only relatively minor decreases in the fibrinolytic activity of the variants. The cumulative results distinguish discrete sections of the NH2 terminal region of the enzyme as determinants of in vivo clearance and fibrinolytic activity of t-PA. In addition, the fibrinolytic activity of a variant containing the substitutions Gln42----Asn, His44----Glu, and Asn117--- Gln, when compared with wild-type t-PA in an in vivo rabbit venous clot lysis model, was found to have similar lytic efficacy at approximately one-fourth the dose. We conclude that decreases in the in vivo clearance of t-PA can result in more potent thrombolytic agents in vivo, even though the in vitro fibrinolytic activity of the enzyme may be somewhat impaired. PMID- 2108144 TI - Role of aspartate 27 of dihydrofolate reductase from Escherichia coli in interconversion of active and inactive enzyme conformers and binding of NADPH. AB - The apoenzyme of wild-type (WT) dihydrofolate reductase (DHRF) from Escherichia coli exists in two conformational states, Et and Ew, which differ in affinity for NADPH and in kinetic competence. Dissociation constants for the binary complex of NADPH with the two conformers differ by over 100-fold (KDt = 0.17 microM, KDw = 22 microM). Rate constants governing the interconversion of conformers are small (t1/2 for Ew----Et = 71 s), and since Ew is not catalytically competent, this conversion is accompanied by an increase in catalytic velocity. The equilibrium proportion of Et in the absence of ligands is 63%, but binding of NADPH greatly increases this proportion, and t1/2 for conversion of Ew.NADPH to Et.NADPH is 30 s. This conformational equilibrium has also been examined in mutant enzyme in which aspartate 27 is replaced by asparagine (D27N E. coli DHFR). Although ASp27 is an active site residue, it does not interact directly with bound NADPH, and in the mutant the rate constant for NADPH binding to Et is unchanged as are the dissociation constants for NADPH complexes with Et or Ew. However, for mutant apoenzyme, the proportion of Et is decreased to 18% in the absence of ligands so that the overall KD for NADPH is increased (0.15 microM for WT E. coli DHFR, 0.68 microM for D27N E. coli DHFR). The lower proportion of Et is due to a decreased rate for Ew----Et (t1/2 = 221 s) and an increased rate for Et----Ew (t1/2 = 50 s versus 120 s for WT E. coli DHFR). PMID- 2108145 TI - Chelation of cytoplasmic Ca2+ increases plasma membrane permeability in murine macrophages. AB - Cytoplasmic free Ca2+ (Ca2+i) was chelated to 10-20 nM in the macrophage cell line J774 either by incubation with quin2 acetoxymethyl ester in the absence of external Ca2+ (Di Virgilio, F., Lew, P.D., and Pozzan, T. (1984) Nature 310, 691 693) or by loading [ethyl-enebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) into the cytoplasm via reversible permeabilization of the plasma membrane with extracellular ATP (Steinberg, T.H., Newman, A.S., Swanson, J.A., and Silverstein, SS.C. (1987) J. Biol. Chem. 262, 8884-8888; Di Virgilio, F., Meyer, B.C., Greenberg, S., and Silverstein, S.C. (1988) J. Cell Biol. 106, 657-666). After removal of ATP from the incubation medium, ATP-permeabilized Ca2+i-depleted macrophages recovered a near-normal plasma membrane potential which slowly depolarized over a 2-4 h incubation at low [Ca2+]i. In both ATP-treated and quin2 loaded cells, depolarization of plasma membrane potential was paralleled by an increase in plasma membrane permeability to low molecular weight aqueous solutes such as eosin yellowish (Mr 692), ethidium bromide (Mr 394), and lucifer yellow (Mr 463). This increased plasma membrane permeability was not accompanied by release of the cytoplasmic marker lactic dehydrogenase for incubations up to 4 h and was likely a specific effect of Ca2+i depletion since it was not caused by: (i) the mere incubation of macrophages with extracellular EGTA, i.e. at near normal [Ca2+]i; and (ii) loading into the cytoplasm of diethylenetriaminepentaacetic acid, a specific chelator of heavy metals with low affinity for Ca2+. Treatment of Ca2+i-depleted cells with direct (phorbol 12 myristate 13-acetate) or indirect (platelet-activating factor) activators of protein kinase C prevented the increase in plasma membrane permeability. Down regulation of protein kinase C rendered Ca2+i-depleted macrophages refractory to the protective effect of phorbol 12-myristate 13-acetate. This report suggests a role for Ca2+i and possibly protein kinase C in the regulation of plasma membrane permeability to low molecular weight aqueous solutes. PMID- 2108146 TI - Translational repression by bacteriophage MS2 coat protein expressed from a plasmid. A system for genetic analysis of a protein-RNA interaction. AB - The coat protein of bacteriophage MS2 is a translational repressor. It inhibits the synthesis of the viral replicase by binding a specific RNA structure that contains the replicase translation initiation region. In order to begin a genetic dissection of the repressor activity of coat protein, a two-plasmid system has been constructed that expresses coat protein and a replicase-beta-galactosidase fusion protein from different, compatible plasmids containing different antibiotic-resistant determinants. The coat protein expressed from the first plasmid (pCT1) represses synthesis of a replicase-beta-galactosidase fusion protein encoded on the other plasmid (pRZ5). Mutations in the translational operator or in coat protein result in constitutive synthesis of the enzyme. This permits the straightforward isolation of mutations in the coat sequence that affect repressor function. Because of the potential importance of cysteine residues for RNA binding, mutations were constructed that substitute serines for the cysteine residues normally present at positions 46 and 101. Both of these mutations result in translational repressor defects. Chromatographic and electron microscopic analyses indicate that the plasmid-encoded wild-type coat protein forms capsids in vivo. The ability of the mutants to adopt and/or maintain the appropriate conformation was assayed by comparing them to the wild-type protein for their ability to form capsids. Both mutants exhibited evidence of improper folding and/or instability as indicated by their aberrant elution behavior on a column of Sepharose CL-4B. Methods were developed for the rapid purification of plasmid-encoded coat protein, facilitating future biochemical analyses of mutant coat proteins. PMID- 2108147 TI - Surfactant protein D is a divalent cation-dependent carbohydrate-binding protein. AB - Surfactant protein D (SP-D, CP4) is a collagenous surfactant-associated glycoprotein synthesized by lung type II epithelial cells. SP-D can be selectively and efficiently eluted from isolated rat surfactant with glucose, maltose, and certain other saccharides. We therefore examined the ability of the purified protein to interact with carbohydrates in vitro. Saccharide-substituted bovine serum albumins (BSA neoglycoproteins) were adsorbed to plastic wells, and binding of purified SP-D was quantified with monospecific antibodies to SP-D using an indirect immunoassay. SP-D showed specific calcium-dependent binding to alpha-D-glucosidophenyl isothiocyanate-BSA and maltosyl-BSA, but negligible binding to beta-D-glucosidophenyl isothiocyanate-BSA or unconjugated BSA. The most efficient inhibitors of SP-D binding were alpha-glucosyl-containing saccharides (e.g. isomaltose, maltose, malotriose). SP-D showed quantitative binding to maltosyl-agarose and was specifically eluted with maltose or EDTA. High affinity binding to maltosyl-BSA was also demonstrated using a solution phase polyethylene glycol precipitation assay. These studies demonstrate that SP D is a calcium dependent lectin-like protein and that the association of SP-D with surfactant is mediated by carbohydrate-dependent interactions with specificity for alpha-glucosyl residues. PMID- 2108148 TI - Structure and synthesis of intracellular proteoglycan in HL-60 human leukemic promyelocytes. AB - The structure, biosynthesis, and metabolism of proteoglycans in the HL-60 human promyelocytes were studied by metabolic labeling in culture with [35S]sulfate, [3H]glucosamine, [3H]serine, and [3H]leucine. These cells synthesize a single predominant species of intracellular proteoglycan with an approximate molecular weight of 100,000. The cells contain about 1 microgram of proteoglycan/million cells. The proteoglycan is turned over within the cells in two apparent pools with half-lives of about 0.6 and 27 h, respectively. The fast pool represents secretion into medium in an apparently intact form, whereas the slow pool represents intracellular degradation to free chondroitin sulfate chains and smaller fragments. The proteoglycan contains a protein core with an apparent Mr on gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of about 20,000-30,000. To the core protein are attached an average of six or seven chondroitin sulfate chains, each with an Mr of about 10,000. The chondroitin sulfate chains contain approximately 85% 4-sulfated and approximately 15% nonsulfated disaccharides. The chondroitin sulfate attachment region of the core protein is essentially resistant to trypsin and elastase, whereas the remainder of the protein core is readily degraded by proteases. The size of the chondroitin sulfate attachment region peptide generated by trypsin was estimated to be approximately 5 kDa. Based on the molecular size, distribution of amino acids, protease susceptibility, and the extent of O-glycosylation, we propose that the intracellular proteoglycan characterized in this study is the translation product of a proteoglycan gene reported to be present in these cells (Stevens, R.L., Avraham, S., Gartner, M.C., Bruns, G.A., Austen, K.E., and Weis, J.H. (1988) J. Biol. Chem. 263, 7287-7291). PMID- 2108149 TI - The polypeptide of immunoglobulin G influences its galactosylation in vivo. AB - To examine the nature of the factors influencing the galactosylation pattern of the heavy chain of murine immunoglobulin G (IgG), cell fusion was performed between a myeloma (P3x63Ag8) and a hybridoma (Sp2HL/Bu) cell line which secrete different IgGs possessing structurally distinct CH2-linked oligosaccharide moieties. The glycosylation patterns of the IgGs of the parental and fused cells were studied. Pronase digestion of the purified heavy chains and subsequent end labeling with fluorescein isothiocyanate produced fluoresceinated glycopeptides which were detected and purified by polyacrylamide gel electrophoresis. Structural information was obtained by enzymatic digestion, lectin affinity chromatography, and methylation analysis. IgGs from both parental lines possessed oligosaccharide units displaying microheterogeneity based upon a common symmetrical biantennary structure terminating in beta-GlcNAc. The structures of both IgGs, however, differed in the pattern of the mono- and digalactosylated components. Clones, selected following the fusion of the parental cells, were expanded; and the individual IgGs were purified. All clones produced homodimeric IgG1 and IgG2b as well as heterodimeric IgG possessing both the gamma 1 and gamma 2b heavy chains. Analysis of the carbohydrate moieties of the gamma 1 chain from the homodimeric and heterodimeric IgGs and of the gamma 2b chain from the heterodimeric molecule demonstrates that the polypeptide structure of the heavy chain influences the terminal galactosylation of the glycan unit at the conserved site of glycosylation of IgGs. PMID- 2108150 TI - Isolation and characterization of calcium binding glycoproteins of cardiac sarcolemmal vesicles. AB - Two major Ca2(+)-binding glycoproteins Mr 120,000 and 100,000 were isolated from 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid -solubilized bovine heart sarcolemma membrane. Peroxidase-conjugated concanavalin A and wheat germ agglutinin lectins bind strongly to the isolated 120- and 100-kDa glycoproteins. Treatment with endoglycosidase F resulted in conversion of the 120-kDa glycoprotein to a form migrating at about 97 kDa. Treatment of the 100-kDa band with endoglycosidase F produced form of about 80 kDa. Endoglycosidase H digestion removes only 5% of the mass of both glycoproteins. the carbohydrate structure of both glycoproteins, is therefore, predicted to be at least 75% complex structure and 25% high mannose or hybrid structure. The 120- and 100-kDa glycoproteins are the major Ca2(+)-binding proteins in the sarcolemma membranes. Intact and endoglycosidase-treated glycoproteins bind 45Ca2+ as analyzed by a 45Ca2+ overlay technique. Using polyclonal antibodies, the 120- and 100-kDa glycoproteins were identified in muscle plasma membranes (ventricles, atria, and uterus smooth muscle). They were, however, not present in non-muscle tissues such as pancreas, liver, and kidney. The 120- and 100-kDa glycoproteins appear to be homologous molecules as judged by their similar V8 protease peptide maps, cross-reactivity with polyclonal antibody, and other physicochemical properties. PMID- 2108151 TI - Release of dialkylglycerol from purple membrane phospholipids by phospholipase D. AB - When the major polar lipid of purple membrane, a dialkyl analogue of phosphatidyl glycerophosphate, is treated with phospholipase D under the usual assay conditions for this enzyme, the reaction yields dialkylglycerol and glycerol bisphosphate, i.e. the kind of products that would be expected from a phospholipase C reaction. The effect is seen both in native purple membranes and with the pure phospholipid in the form of liposomes. The specific activity and kinetic parameters Km and Vmax of phospholipase D for the purple membrane phospholipid are similar to those for egg phosphatidylcholine. The presence of phospholipase C impurities in the phospholipase D preparations has been ruled out as an explanation for the above observations. A hypothesis is suggested, taking into account the peculiar headgroup structure of the bacterial lipid, to explain the seemingly anomalous enzyme behavior. PMID- 2108152 TI - The human oxytocin gene promoter is regulated by estrogens. AB - Gonadal steroids affect brain function primarily by altering the expression of specific genes, yet the specific mechanisms by which neuronal target genes undergo such regulation are unknown. Recent evidence suggests that the expression of the neuropeptide gene for oxytocin (OT) is modulated by estrogens. We therefore examined the possibility that this regulation occurred via a direct interaction of the estrogen-receptor complex with cis-acting elements flanking the OT gene. DNA-mediated gene transfer experiments were performed using Neuro-2a neuroblastoma cells and chimeric plasmids containing portions of the human OT gene 5'-glanking region linked to the chloramphenicol acetyltransferase gene. We identified a 19-base pair region located at -164 to -146 upstream of the transcription start site which is capable of conferring estrogen responsiveness to the homologous as well as to a heterologous promoter. The hormonal response is strictly dependent on the presence of intracellular estrogen receptors, since estrogen induced stimulation occurred only in Neuro-2a cells co-transfected with an expression vector for the human estrogen receptor. The identified region contains a novel imperfect palindrome (GGTGACCTTGACC) with sequence similarity to other estrogen response elements (EREs). To define cis-acting elements that function in synergism with the ERE, sequences 3' to the ERE were deleted, including the CCAAT box, two additional motifs corresponding to the right half of the ERE palindrome (TGACC), as well as a CTGCTAA heptamer similar to the "elegans box" found in Caenorhabditis elegans. Interestingly, optimal function of the identified ERE was fully independent of these elements and only required a short promoter region (-49 to +36). Our studies define a molecular mechanism by which estrogens can directly modulate OT gene expression. However, only a subset of OT neurons are capable of binding estrogens, therefore, direct action of estrogens on the OT gene may be restricted to a subpopulation of OT neurons. PMID- 2108153 TI - Purification and characterization of photosystem I and photosystem II core complexes from wild-type and phycocyanin-deficient strains of the cyanobacterium Synechocystis PCC 6803. AB - Highly photoactive Photosystem I (PS I) and Photosystem II (PS II) core complexes have been isolated from the cyanobacterium Synechocystis Pasteur Culture Collection (PCC) 6803 and a phycocyanin-deficient mutant, enriched in PS II. Cell breakage using glass beads was followed by sucrose density gradient centrifugation and two high-performance liquid chromatography steps involving anion-exchange and hydroxyapatite. The PS I core complex has an apparent molecular mass of 300 +/- 20 kDa (including a detergent shell of about 50 kDa) and contains subunits of approximately 60, approximately 60, 18.5, 18.5, 16, 15, 10.5, 9.5, and 6.5 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblots; its antenna size is 75 +/- 5 chlorophyll/P-700. The PS II core complex has an apparent molecular mass of 310 +/- 20 kDa (including the detergent shell); subunits of 43, 37, 33, 29, and 10-11 kDa were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The antenna size of the average PS II complex is 45 +/- 5 chlorophyll/primary quinone electron acceptor (QA). This preparation procedure also yields, as a byproduct, a highly purified cytochrome b6f complex. This complex contains four subunits of 38, 24, 19, and 15 kDa and b- and c-type cytochromes in a ratio of 2:1. Its apparent molecular mass of 180 +/- 20 kDa (including the detergent shell) is consistent with a monomeric complex. PMID- 2108154 TI - Topography of the human factor VIII-von Willebrand factor complex. AB - Factor VIII circulates in noncovalent complex with von Willebrand factor (vWf). The topography of this complex was evaluated by fluorescence energy transfer using factor VIII subunits modified with N-(1-pyrenyl)maleimide (NPM; fluorescence donor) and vWf-derived fragments modified with 7-diethylamino-3-[4' maleimidylphenyl]-4-methyl coumarin (CPM; fluorescence acceptor). Results from a previous study indicated an interfactor VIII subunit distance of 20 A separating Cys528 and Cys1858 in the factor VIII heavy and light chains, respectively (Fay, P.J., and Smudzin, T. M. (1989) J. Biol. Chem. 264, 14005-14010). Fluorophore modification of the vWf SPIII homodimer (residues 1-1365) indicated multiple attachment sites at Cys126/135/1360 as determined from sequence analysis of fluorescent tryptic peptides derived from the modified protein. Based upon donor quenching data, an interfluorophore distance of approximately 28 A was calculated separating NPM-factor VIII light chain or factor VIII reconstituted from NPM light chain plus unmodified heavy chain, from CPM-SPIII. A similar value (29 A) was obtained for NPM-light chain paired with CPM-SPIII-T4 (vWf residues 1-272), suggesting that donor quenching resulted primarily from modified residue(s) Cys126/135 in the acceptor. No energy transfer was observed for the NPM-heavy chain/CPM-SPIII pairing. However, when NPM-heavy chain was reassociated with unmodified light chain prior to reaction with CPM-SPIII or CPM-SPIII-T4, energy transfer was observed with calculated interfluorophore distances of approximately 31 and 34 A, respectively. Levels of acceptor resulting in maximal donor quenching suggested an equimolar stoichiometry of factor VIII (light chain)/vWf fragment in the reconstituted complexes. These results indicate a close spatial arrangement among the A3 domain of factor VIII light chain, the A2 domain of factor VIII heavy chain, and the NH2 terminus region of vWf in the factor VIII vWf complex. PMID- 2108155 TI - Transfer and expression of a murine UDP-Gal:beta-D-Gal-alpha 1,3 galactosyltransferase gene in transfected Chinese hamster ovary cells. Competition reactions between the alpha 1,3-galactosyltransferase and the endogenous alpha 2,3-sialyltransferase. AB - The cDNA encoding a murine UDP-Gal:beta-D-Gal-alpha 1,3-galactosyltransferase has recently been cloned and sequenced using a transient expression method (Larsen, R.D., Rajan, V.P., Ruff, M.M., Kukowska-Latallo, J., Cummings, R.D., and Lowe, J.B. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 8227-8231). This report describes the construction and analysis of a Chinese hamster ovary (CHO) cell line in which in vitro expression alpha 1,3-galactosyltransferase activity has been achieved via transfer and expression of the murine alpha 1,3-galactosyltransferase gene. A primary aim of this research was to explore the role of the alpha 1,3 galactosyltransferase in regulating glycoprotein and glycolipid biosynthesis. CHO cells were cotransfected with murine genomic DNA fragments from F9 cells and plasmid DNA containing a resistance gene to the antibiotic G418. Cells resistant to G418 were then selected for expression of surface glycoconjugates containing terminal alpha 1,3-galactosyl residues by isolating cells bound to immobilized Griffonia simplicifolia-I-B4, a lectin which binds to alpha 1,3-galactosyl residues. A positive, stable transfectant clone, designated Clone 3, was obtained and analyzed for expression of the murine of alpha 1,3-galactosyltransferase. Fluorescence-activated cell sorting demonstrated that Clone 3, but not parental, CHO cells bound significant amounts of fluorescein isothiocyanate-labeled G. simplicifolia-I-B4. Southern and Northern blot analyses using the murine alpha 1,3-galactosyltransferase cDNA demonstrated that clone 3, but not parental, CHO cells contain murine alpha 1,3-galactosyltransferase genomic DNA sequences, and express a homologous transcript that comigrates with the authentic 3.6 kilobase alpha 1,3-galactosyltransferase murine mRNA. Enzyme assays confirmed that clone 3, but not parental CHO cells, contained the alpha 1,3-galactosyltransferase activity and that the level of activity is comparable to that found in F9 cells. [3H]Galactose-labeled glycopeptides and glycolipids were obtained from metabolically radiolabeled parental and Clone 3 cells and were analyzed for the presence of terminal alpha 1,3-galactosyl residues. Complex-type, Asn-linked oligosaccharides from both parental and Clone 3 cells contain the repeating disaccharide [3Gal beta 1, 4GlcNAc beta 1]n or poly-N-acetyllactosamine sequences, but only the poly-N-acetyllactosamine chains from clone 3 cells contained the terminal sequence Gal alpha 1,3Gal beta 1,4GlcNAc beta 1 R.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2108156 TI - Chemical modification of adenylosuccinate synthetase from Escherichia coli by pyridoxal 5'-phosphate. Identification of an active site lysyl residue. AB - Incubation of adenylosuccinate synthetase from Escherichia coli with low concentrations of pyridoxal 5'-phosphate (PLP) resulted in a rapid loss of activity (92%), concomitant with the formation of a Schiff base. The inactivation of the enzyme by PLP is apparently first order with respect to PLP. The pseudo first order rate constant, Kapp, showed a hyperbolic dependence on the concentration of PLP, indicating that a kinetically significant PLP.enzyme intermediate is formed during the inactivation process. Stoichiometry and peptide isolation studies showed that 2 lysine residues were modified during reaction of the enzyme with PLP. The three substrates of adenylosuccinate synthetase (GTP, IMP, and aspartate) showed different effects in their ability to protect the enzyme against PLP inactivation. Complete protection of the enzyme against inactivation can be observed only in the presence of high concentrations of GTP. One lysine residue was protected under these conditions. In contrast to GTP, addition of the other two substrates either alone or together to reaction mixtures did not render protection. Peptide mapping by digesting the enzyme with trypsin revealed that the lysine shielded by GTP is Lys140. Replacing the Lys140 with Ile140 by site-directed mutagenesis resulted in total loss of the activity. These results suggest that Lys140 may play an important role in enzymatic activity. PMID- 2108157 TI - Physicochemical and immunological studies on mammalian 5'-deoxy-5' methylthioadenosine phosphorylase. AB - 5'-Deoxy-5'-methylthioadenosine phosphorylase (MTAase) was purified to homogeneity (10,000-fold) from bovine liver with a recovery of 12%. The pure protein shows a molecular weight of about 98,000 +/- 3,000 and is composed of three apparently identical subunits. Several physicochemical features have been investigated including hydrodynamic properties, amino acid composition, and secondary structure. In particular, the CD spectrum of the protein indicates a very low alpha-helical content and a large percent of beta-structure and random coil. The pure protein was used to raise specific rabbit antisera but, because of the scarce antigenic properties of the native enzyme, different chemically modified forms were prepared and employed as immunogens. Among the antibodies obtained, those to keyhole limpet hemocyanin-MTAase recognize both the native and the denatured enzyme and are also active against the human protein. Therefore, they were employed as a tool to investigate the occurrence of inactive forms of MTAase in two human malignant cell lines lacking this enzymatic activity. The results obtained with K562 and Jurkat cells indicate that the protein is absent in these phosphorylase-deficient cell lines. PMID- 2108158 TI - Distinct guanine nucleotide binding and release properties of the three Gi proteins. AB - The native pertussis toxin sensitive GTP-binding proteins (Gi proteins) were individually resolved, and their guanine nucleotide binding and release properties were studied. Gi2 and Gi3, the two major GTP-binding proteins of human erythrocytes, were purified to apparent homogeneity by fast protein liquid chromatography. Gi1 was purified from bovine brain. The three proteins bound 0.6 0.85 mol of guanosine 5'-O-(thio-triphosphate (GTP gamma S)/mol of protein with similar affinities (KD(app) = 50-100 nM). The rate of [35S]GTP gamma S binding to Gi2 was 5-8-fold faster than to Gi1 or Gi3 at 2 mm Mg2+. There were no observable differences in the binding characteristics between bovine brain Gi1 and human erythrocyte Gi3. At 50 mM Mg2+, all three Gi proteins exhibited fast binding, although Gi1 and Gi3 were marginally slower than Gi2. All three Gi proteins exhibited different rates of [32P]GDP release at 2 mM Mg2+. GDP release from Gi2 was severalfold faster than that from Gi1 or Gi3. GDP release rates from Gi1 and Gi3 were similar, although Gi3 was somewhat (60-80%) faster than Gi1. These data indicate that rates of GDP release and GTP binding may be independently regulated for these three proteins and that the relative proportions of Gi2/Gi1 or Gi2/Gi3 will be a crucial factor in determining the kinetics of signal transduction through Gi-coupled effectors. PMID- 2108159 TI - Hepatic lipase: site-directed mutagenesis of a serine residue important for catalytic activity. AB - Hepatic lipase (HL) is a member of the lipoprotein lipase/pancreatic lipase gene family and is believed to function in processing of intermediate and high density lipoproteins. As a lipase, HL is presumed to have a lipid interfacial binding domain, distinct from the esterase catalytic site, orienting the enzyme at aqueous-lipid interfaces and resulting in activation of esterase activity. However, the structural domains responsible for these separate functions have not been identified. Amino acid sequence homology to serine proteases, thioesterases and other lipases, identified Ser147 of rat HL as part of a highly conserved element in an esterase gene family. In order to better define the function of this domain in HL, site-directed mutagenesis was utilized to produce mutant cDNAs with amino acid substitutions for Ser147, Ser133, or Ser228. Following injection of Xenopus oocytes with SP6 transcripts for normal or mutant HL, media from the oocytes were assayed for lipolytic activity and immunoprecipitable HL protein. Mutations of Ser133 and Ser228 produced no decrease in activity whereas the mutant protein in which Ser147 was replaced with glycine had little, if any activity against emulsified triolein substrates. Replacing HL Ser147 with glycine also resulted in a protein with little or no measurable activity for tributyrin, a substrate which does not provide a lipid interface. These results suggest that Ser147 in rat HL is either located at the catalytic site or is required for maintaining the structural integrity of the catalytic site. PMID- 2108160 TI - Guanine nucleotide binding properties of the mammalian RalA protein produced in Escherichia coli. AB - The simian ralA cDNA was inserted in a ptac expression vector, and high amounts of soluble ral protein were expressed in Escherichia coli. The purified p24ral contains 1 mol of bound nucleotide/mol of protein that can be exchanged against external nucleotide. The ral protein exchanges GDP with a t 1/2 of 90 min at 37 degrees C in the presence of Mg2+, and has a low GTPase activity (0.07 min-1 at 37 degrees C). We have also studied its affinity for various guanine nucleotides and analogs. NMR measurements show that the three-dimensional environment around the nucleotide is similar in p21ras and p24ral. In addition to these studies on the wild-type ral protein, we used in vitro mutagenesis to introduce substitutions corresponding to the Val12, Val12 + Thr59, and Leu61 substitutions of p21ras. These mutant ral proteins display altered nucleotide exchange kinetics and GTPase activities, however, the effects of the substitutions are less pronounced than in the ras proteins. p24ralVal12 + Thr59 autophosphorylates on the substituted Thr, as a side reaction of the GTP hydrolysis, but the rate is much lower than those of the Thr59 mutants of p21ras. These results show that ras and ral proteins have similar structures and biochemical properties. Significant differences are found, however, in the contribution of the Mg2+ ion to GDP binding, in the rate of the GTPase reaction and in the sensitivity of these two proteins to substitutions around the phosphate-binding site, suggesting that the various "small G-proteins" of the ras family perform different functions. PMID- 2108161 TI - Cleavage of spermidine as the first step in deoxyhypusine synthesis. The role of NAD. AB - The biosynthesis of deoxyhypusine (N-(4-aminobutyl)lysine) occurs by the transfer of the 4-aminobutyl moiety of spermidine to a specific lysine residue in a precursor of eukaryotic translation initiation factor 4D (eIF-4D). Deoxyhypusine synthase, the enzyme that catalyzes this reaction, was purified approximately 700 fold from rat testis. The Km values for the substrates, spermidine, the eIF-4-D precursor protein, and NAD+, were estimated as approximately 1, 0.08, and 30 microM, respectively. After incubation of partially purified enzyme with [1,8 3H]spermidine, NAD+, and the eIF-4D precursor, equal amounts of radioactivity were found in free 1,3-diaminopropane and in protein-bound deoxyhypusine. However, when the protein substrate (eIF-4D precursor) was omitted, radioactivity was found in 1,3-diaminopropane and in delta 1-pyrroline in nearly equal quantities, providing evidence that the cleavage of spermidine occurs, albeit at a slower rate, in the absence of the eIF-4D precursor. That NAD+, which is required for this reaction, functions as the hydrogen acceptor was demonstrated by the fact that radioactivity from spermidine labeled with 3H at position 5 is found in NADH as well as in delta 1-pyrroline. Transfer of this hydrogen from spermidine to the re face of the nicotinamide ring of NAD+, as determined by the use of dehydrogenases of known stereospecificity, defines the first step of deoxyhypusine synthesis as a pro-R, or A, stereospecific dehydrogenation. Based on these findings, an enzyme mechanism involving imine intermediate formation is proposed. PMID- 2108162 TI - Epidermal growth factor enhances glomerular mesangial cell soluble phospholipase A2 activity. AB - We have previously characterized a hormonally regulated soluble form of phospholipase A2 (PLA2) in the cultured renal mesangial cell which is similar and possibly identical to the major form in rat kidney. In an attempt to further characterize the mechanisms of regulation of this enzyme we have used epidermal growth factor (EGF), which does not activate polyphosphoinositide-specific phospholipase C in these cells. EGF-enhanced PLA2 activity as assayed by the ability of the soluble extracts of cells to cleave arachidonic acid from the sn-2 position of phosphatidylcholine and phosphatidylethanolamine. This represents a direct demonstration of EGF-induced PLA2 activation which is preserved in a cell free extract. Phorbol myristate acetate (PMA), as well as 1-oleoyl-2 acetylglycerol, also enhanced PLA2 activity. By contrast, the calcium ionophore A23187 had no effect on extract PLA2 activity. The EGF- and PMA-induced enhanced activity was recovered following fractionation by Mono-Q anion exchange chromatography. The peak of activity comigrated for both agonists, suggesting that both EGF and PMA stimulated the same form of the enzyme. Down-regulation of protein kinase C by pretreatment with PMA resulted in loss of the PMA-induced, but not the EGF-induced, enhancement in PLA2 activity. 8-Bromo-cAMP had no effect upon the PLA2 activity, and did not modulate the EGF effect. Pertussis toxin induced G protein ADP-ribosylation but had no effect upon PLA2 activity, and did not alter the EGF effect. In summary, EGF results in a stable modification of PLA2 activity in glomerular mesangial cells. This enhanced activity is independent of polyphosphoinositide hydrolysis, insensitive to protein kinase C down-regulation, and is not affected by cAMP or pertussis toxin pretreatment of the cells. PMID- 2108163 TI - Diffraction quality crystals of lysin from spermatozoa of the red abalone (Haliotis rufescens). AB - Single crystals of the protein lysin (Mr = 16,070) from the spermatozoa of the red abalone (Haliotis rufescens) have been obtained by the vapor diffusion technique, using as precipitants a 32.5% saturated solution of (NH4)2SO4 (incubation at 18 degrees C) or a 5% w/v polyethyleneglycol 8000 solution (incubation at 29 degrees C), both in Bis-Tris-iminodiacetic acid buffers of pH 7.0. The addition to the droplets of EDTA, other carboxylate-containing polyanions, and/or organic solvents improved the size and quality of the crystals and, especially with (NH4)2SO4, addition of EDTA, and/or organic solvents produced a change in crystal habit which resulted in crystals more elongated in the b direction. The crystals belong to the orthorhombic space group P2(1)2(1)2(1) with a = 52.3 A, b = 46.0 A, and c = 81.5 A and one molecule per asymmetric unit. The crystals diffract to 2.3 A resolution. The molecular structure of lysin is relevant to the nonenzymatic mechanism by which the protein dissolves a hole in the egg vitelline layer during fertilization. PMID- 2108164 TI - Sodium dodecyl sulfate activation of a plant polyphenoloxidase. Effect of sodium dodecyl sulfate on enzymatic and physical characteristics of purified broad bean polyphenoloxidase. AB - Latent broad bean polyphenoloxidase was purified and shown to be activated by sodium dodecyl sulfate (SDS). Further characterization of the enzyme was carried out in the presence and absence of SDS. Activation of the enzyme increased in a sigmoidal manner with increasing SDS concentrations up to a maximum of 1.75 mM. The presence of SDS eliminated a low pH optimum induced by acid shocking. Increased thermolability of the enzyme was observed in the presence of SDS as well as an increased binding of [14C]dihydroxy-phenylalanine. Size exclusion chromatography on high performance liquid chromatography showed that the size and apparent molecular mass of the enzyme were slightly altered in the presence (48 kDa) versus absence (47 kDa) of SDS. Although the estimations were larger than those obtained by size exclusion techniques, no large differences in molecular weight were observed after sedimentation equilibrium of the enzyme in the presence (53.9 kDa) and absence (52.3 kDa) of SDS. Relative electrophoretic mobility and intrinsic fluorescence of tyrosine and tryptophan residues increased in a complex fashion as the SDS concentration was increased. Plateau regions in these latter experiments corresponded to concentrations of SDS needed for activation. The ability of SDS to activate the enzyme alters both its enzymatic and physical characteristics and suggests that a limited conformational change, due to binding of small amounts of SDS, may induce or initiate the activation of latent enzyme. PMID- 2108165 TI - Differential turnover of phospholipid acyl groups in mouse peritoneal macrophages. AB - Phospholipid acyl turnover was assessed in mouse peritoneal exudate cells which consisted primarily of macrophages. The cells were incubated for up to 5 h in media containing 40% H218O, and uptake of 18O into ester carbonyls of phospholipids was determined by gas chromatography-mass spectrometry of hydrogenated methyl esters. The uptake was highest in choline phospholipids and phosphatidylinositol, less in ethanolamine phospholipids, and much less in phosphatidylserine. Acyl groups at the sn-1 and sn-2 positions of diacyl glycerophospholipids, including arachidonic and other long-chain polyunsaturated fatty acids, acquired 18O at about the same rate. Acyl groups of alkylacyl glycerophosphocholine exhibited lower rates of 18O uptake, and acyl groups of ethanolamine plasmalogens (alkenylacyl glycerophosphoethanolamines) acquired only minimal amounts of 18O within 5 h, indicating a low average acyl turnover via free fatty acids. Pulse experiments with exogenous 3H-labeled arachidonic acid supported the concept that acylation of alkenyl glycerophosphoethanolamine occurs by acyl transfer from other phospholipids rather than via free fatty acids and acyl-CoA. The 18O content of intracellular free fatty acids increased gradually over a 5-h period, whereas in extracellular free fatty acids it reached maximal 18O levels within the first hour. Arachidonate and other long-chain polyunsaturated fatty acids were found to participate readily in deacylation reacylation reactions but were present only in trace amounts in the free fatty acid pools inside and outside the cells. We conclude that acyl turnover of macrophage phospholipids through hydrolysis and reacylation is rapid but tightly controlled so that appreciable concentrations of free arachidonic acid do not occur. PMID- 2108166 TI - Occurrence of chondroitin sulfate E in glycosaminoglycan isolated from the body wall of sea cucumber Stichopus japonicus. AB - Glycosaminoglycan was isolated from the body wall of sea cucumber Stichopus japonicus by a method consisting of enzymatic digestion, gel filtration, and ion exchange chromatography. One gram of sea cucumber glycosaminoglycan was composed of 2.50 mmol of sulfate, 0.47 mmol of N-acetylgalactosamine (GalNAc), 0.53 mmol of glucuronic acid (GlcA), 1.73 mmol of fucose, and a small amount of peptide. When mildly hydrolyzed with 0.1 N H2SO4, this glycosaminoglycan released two products, one consisting of fucose plus sulfate and the other of fucose only. Partially hydrolyzed glycosaminoglycan thus obtained was composed of sulfate, GalNAc, GlcA, and fucose at a molar ratio of 3:2:2:1. Partially hydrolyzed glycosaminoglycan was easily digested with chondroitinase AC II. In ion-exchange chromatography, the digest exhibited four sharp peaks whose retention times agreed with those of unsaturated 0-(delta Di-0S), mono-(delta Di-4S and delta Di 6S), and di-(delta Di-SE) sulfated disaccharide, respectively. The disaccharide unit of sea cucumber glycosaminoglycan was composed of 22.4% chondroitin sulfate E, 11.2% chondroitin, 10.4% chondroitin 4-sulfate, and 56.0% chondroitin 6 sulfate. PMID- 2108167 TI - Characterization of a modified human tissue plasminogen activator comprising a kringle-2 and a protease domain. AB - To study structure/function relationships of tissue plasminogen activator (t-PA) activity, one of the simplest modified t-PA structures to activate plasminogen in a fibrin-dependent manner was obtained by constructing an expression vector that deleted amino acid residues 4-175 from the full-length sequence of t-PA. The expression plasmid was introduced into a Syrian hamster cell line, and stable recombinant transformants, producing high levels of the modified plasminogen activator, were isolated. The resulting molecule, mt-PA-6, comprising the second kringle and serine protease domains of t-PA, produced a doublet of plasminogen activator activity having molecular masses of 40 and 42 kDa. The one-chain mt-PA 6 produced by cultured Syrian hamster cells was purified in high yield by affinity and size exclusion chromatography. The purified mt-PA-6 displayed the same two types of microheterogeneity observed for t-PA. NH2-terminal amino acid sequencing demonstrated that one-chain mt-PA-6 existed in both a GAR and a des GAR form. Purified mt-PA-6 also existed in two glycosylation forms that accounted for the 40- and 42-kDa doublet of activity produced by the cultured Syrian hamster cells. Separation of these two forms by hydrophobic interaction chromatography and subsequent tryptic peptide mapping demonstrated that both forms contained N-linked glycosylation at Asn448; in addition, some mt-PA-6 molecules were also glycosylated at Asn184. Plasmin treatment of one-chain mt-PA 6 converted it to a two-chain molecule by cleavage of the Arg275-Ile276 bond. This two-chain mt-PA-6, like t-PA, had increased amidolytic activity. The fibrinolytic specific activities of the one- and two-chain forms of mt-PA-6 were similar and twice that of t-PA. The plasminogen activator activity of one-chain mt-PA-6 was enhanced greater than 80-fold by CNBr fragments of fibrinogen, and the one-chain enzyme lysed human clots in vitro in a dose-dependent manner. The ability to produce and purify a structurally simple plasminogen activator with desirable fibrinolytic properties may aid in the development of a superior thrombolytic agent for the treatment of acute myocardial infarction. PMID- 2108168 TI - Covalent binding of arachidonic acid metabolites to human platelet proteins. Identification of prostaglandin H synthase as one of the modified substrates. AB - The covalent modification of proteins by metabolites of arachidonic acid (AA) was investigated in human platelets. Following incubation of washed human platelets with radiolabeled AA, ethanol precipitation of the proteins, and lipid extraction by organic solvents, a small fraction of the radioactivity added (0.3%) was tightly bound to the protein pellet. A dozen labeled protein bands were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Exhaustive hydrolysis of platelet proteins by proteases released an amphipathic radiolabeled material which had a chromatographic behavior similar to that of a known peptidolipid, leukotriene C4. These findings suggest a covalent nature for the observed binding. This binding was specific for AA since palmitate, myristate, or linoleate did not bind to a significant extent. It involved products of both cyclooxygenase and lipoxygenase pathways: it was indeed inhibited to a greater extent by eicosatetraynoic acid than by indomethacin. The protein-associated radioactivity was increased by the thromboxane synthase inhibitor dazoxiben. Indomethacin completely abolished this increase in binding, which could not be reproduced by exogenous prostaglandin (PG) E2, F2 alpha, or D2, and might thus involve PGG2 and/or PGH2. Diamide, an agent known to inhibit the reduction of 12 hydroperoxyeicosatetraenoic acid in platelets, produced an increase of the covalent binding, which was abolished by eicosatetraynoic acid but not by indomethacin: this suggests that the lipoxygenase product bound was 12 hydroperoxyeicosatetraenoic acid or a by-product. Dazoxiben and diamide produced distinct patterns of protein labeling after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One labeled band had a Mr of 70,000 as the PGH synthase monomer. Addition of AA at 17 microM enhanced the labeling of this band, while 100 microM was inhibitory. Labeling of this band was also induced by thrombin in prelabeled platelets. Two monoclonal antibodies against PGH synthase caused immune precipitation of a 70-kDa labeled protein in homogenates of [3H]AA-labeled platelets. PGH synthase, purified from ram seminal vesicles, was covalently modified after incubation with [3H]AA: this labeling was almost completely abolished by indomethacin. As much as 40% of platelet PGH synthase was covalently modified after incubation with 17 microM AA. It can be concluded that in intact platelets PGH synthase is covalently modified by an eicosanoid following incubation with exogenous AA or after AA mobilization from phospholipids by thrombin. PMID- 2108169 TI - The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases. AB - Acetylation of Ser-530 of sheep prostaglandin endoperoxide (PGG/H) synthase by aspirin causes irreversible inactivation of the cyclooxygenase activity of the enzyme. To determine the catalytic function of the hydroxyl group of Ser-530, we used site-directed mutagenesis to replace Ser-530 with an alanine. Cos-1 cells transfected with expression vectors containing the native (Ser-530) or mutant (Ala-530) cDNAs for sheep PGG/H synthase expressed comparable cyclooxygenase and hydroperoxidase activities. Km values for arachidonate (8 microM) and ID50 values for reversible inhibition by the cyclooxygenase inhibitors, flurbiprofen (5 microM), flufenamate (20 microM), and aspirin (20 mM), were also the same for both native and mutant PGG/H synthases; however, only the native enzyme was irreversibly inactivated by aspirin. Thus, the "active site" Ser-530 of PGG/H synthase is not essential for catalysis or substrate binding. Apparently, acetylation of native PGG/H synthase by aspirin introduces a bulky sidechain at position 530 which interferes with arachidonate binding. In related studies, a cDNA for mouse PGG/H synthase was cloned and sequenced. A sequence of 35 residues with Ser-530 at the midpoint was identical in the two proteins. Thus, Ser-530 does lie in a highly conserved region, probably involved in cyclooxygenase catalysis. Sequence comparisons of mouse and sheep PGG/H synthase also provided information about the heme-binding site of the enzyme. The sheep HYPR sequence (residues 274-277), which had been proposed to form a portion of the distal heme binding site, is not conserved in the mouse PGG/H synthase, suggesting that this region is not the distal heme-binding site. One sequence, TIWLREHNRV (residues 303-312 of the sheep enzyme), is very closely related to the sequence TLW(L)LREHNRL common to thyroid peroxidase and myeloperoxidase. The histidine in this latter sequence is the putative axial heme ligand of these peroxidases. We suggest that the histidine (His-309) of sheep PGG/H synthase sequence is the axial heme ligand of this enzyme. PMID- 2108170 TI - Down-regulation of Gi sub-types by prolonged incubation of adipocytes with an A1 adenosine receptor agonist. AB - We have reported previously that prolonged incubation of adipocytes with (-)-N6 phenylisopropyl adenosine (PIA) (an A1 adenosine receptor agonist) down-regulates A1 adenosine receptors. There was a concomitant decrease in pertussis toxin catalyzed ADP-ribosylation of a 41-kDa peptide thought to be the alpha-subunit of Gi. To determine whether this represents true down-regulation of the G-protein, and if so which of the three known forms of Gi are down-regulated, we have used antipeptide antisera specific for Gi alpha-subunits. Serum SG1 recognizes alpha i1 and -2, I1C recognizes only alpha i1, and I3B recognizes alpha i3. Rat adipocytes were maintained in primary culture for up to 7 days with 0-1000 nM PIA. Crude membrane preparations were analyzed by Western blots. There was almost complete loss of alpha i1 and -3, and about 50% loss of alpha i2 from PIA-treated cells. The loss of each alpha i was detectable after 24 h with 300 nM PIA and maximal by 4 days. After 4 days, down-regulation was detectable with 3 nM and maximal with 100 nM PIA. Antiserum BN2 demonstrated approximately 50% loss of G protein beta-subunits in cells treated with 300 nM PIA for 4 days. When cells were incubated for 4 days with 300 nM PIA and then washed to remove PIA, alpha i1, -2, and -3 and beta-subunits returned to control levels within 5 days. Antiserum CS1 detected normal amounts of both the 43- and 47-kDa forms of Gs alpha in PIA-treated cells. We conclude that Gi alpha-subunits are down-regulated along with the adenosine receptor in rat adipocytes. PMID- 2108171 TI - Analysis of glycosaminoglycan substitution in decorin by site-directed mutagenesis. AB - Posttranslational glycosaminoglycan attachment to decorin, a chondroitin/dermatan sulfate proteoglycan, was studied by expression of a wild-type decorin cDNA and several mutagenized forms in two types of mammalian cells. Transfection of the wild-type cDNA resulted in the synthesis of an authentic chondroitin/dermatan sulfate proteoglycan similar to the decorin molecule synthesized by cultured human fibroblasts. Conversion of the serine residue that serves as the attachment site for the sole glycosaminoglycan chain in decorin to a threonine residue greatly reduced the efficiency of the glycosaminoglycan substitution. Less than 10% of the threonine-mutated core protein acquired a glycosaminoglycan chain, whereas most of the core protein was secreted without such substitution. Expression of cDNA in which an alanine residue had been introduced into the substituted serine position resulted in the secretion of core protein with no detectable glycosaminoglycan. Conversion to alanine of either one of the glycine residues that are adjacent to the substituted serine yielded the proteoglycan form of decorin. These results show that the xylosyltransferase responsible for the initiation of the glycosaminoglycan chain on the core protein can use a threonine residue for this substitution instead of a serine residue, but that such substitution is only partial, creating a "part-time" proteoglycan. Moreover, variations are possible in the sequence context of a glycosaminoglycan substituted serine residue without loss of glycosaminoglycan substitution. The conformation of the substitution site may therefore be important for xylosyltransferase recognition. PMID- 2108172 TI - Dexamethasone-induced killing of neoplastic cells of lymphoid derivation: lack of early calcium involvement. AB - The role of calcium influx in dexamethasone-induced fragmentation of DNA was studied in the glucocorticoid-sensitive human lymphoid line of T cell derivation (CEM-C7). Reduction of calcium content in the medium or the use of EGTA increased DNA fragmentation and appeared to slightly enhance the effect of dexamethasone. Incubation of isolated nuclei in the presence of high concentrations of calcium did not bring about significant DNA fragmentation. Calmidazolium, an antagonist of calmodulin dependent reactions did not reduce the sensitivity of CEM-C7 cells to dexamethasone nor did it modify the response to dexamethasone of the resistant CEM-C1 line. It appears that in contrast to rodent thymocytes, massive calcium influx is not per se responsible for the initiation of directed cell killing (apoptosis). PMID- 2108173 TI - Reprogramming of gene expression in postischemic rat liver: induction of proto oncogenes and hsp 70 gene family. AB - Steady-state levels of messenger RNA (mRNA) for different members of the heat shock protein 70 gene family were studied in rat livers reperfused after non necrogenic ischemia. The expression of constitutive hsc 73 gene decreases during ischemia, returns to normal upon reperfusion, and increases 4 hr after restoration of blood flow. Reperfusion induces the expression of another hsp 70 gene family member (the so-called inducible hsp 70 gene), which remains at high levels for at least 7 hr. The induction of hsp 70 family genes is preceded by activation of the cellular oncogene c-fos, the most prompt change in gene expression detected in reperfused liver. Run-on experiments demonstrate that the increased expression of these genes is largely dependent on activation of transcription. Changes in the amount of c-myc and ornithine decarboxylase mRNA are not evident, while the level of the mRNA for glucose-regulated protein GRP 78 increases later, concurrent with the onset of the acute phase response to surgical trauma. Analysis of polysomal and nonpolysomal fractions from sucrose gradients indicates that in postischemic liver, hsp 70 and hsc 73 mRNA are rapidly engaged on light polysomal or nonpolysomal complexes and are later shifted to polysomes. Albumin mRNA displays the same behavior, indicating that hsp 70 mRNA are not preferentially translated and that increased transcription is the major mechanism for enhanced hsp synthesis in postischemic liver. Damage by active oxygen species, pressure overload, and derangements of protein synthesis is likely to include the causative factors of increased expression of c-fos and the hsp 70 gene family in postischemic reperfused liver. PMID- 2108174 TI - Regulation of hexose transport in respiration deficient hamster lung fibroblasts. AB - The transport of [3H]2-deoxy-D-glucose (2DG) and [3H]3-O-methyl-D-glucose (3-OMG) was elevated in a respiration deficient (NADH coenzyme Q [Co Q] reductase deficient) Chinese hamster lung fibroblast cell line (G14). This sugar transport increase was related to an increased Vmax for 2DG transport, 26.9 +/- 4.2 nmoles 2DG/mg protein/30 sec in the G14 cell line vs 9.5 +/- 0.6 nmoles 2DG/mg protein/30 sec in the parental V79 cell line. No differences were observed in their respective Km values for 2DG transport (3.9 +/- .6 vs. 3.0 +/- .13 mM). Factors which increase sugar transport (e.g., glucose deprivation, serum or insulin exposure) or decrease sugar transport (e.g., serum deprivation) in the parental V79 cell line had little effect on sugar transport in the G14 respiration deficient cell lines. Amino acid transport, specific 125I-insulin binding to cells, and insulin-stimulated DNA synthesis, however, were similar in both cell lines. Exposure of both cell lines to varying concentrations of cycloheximide (0.1-50 micrograms/ml) for 4 h resulted in differential effects on 2DG transport. In the parental cell line (V79) low cycloheximide concentrations resulted in decreased 2DG transport, while higher concentrations (greater than or equal to 1 microgram/ml) resulted in elevated 2DG transport. In the G14 cell line, 2DG transport decreased at all concentrations of cycloheximide (up to 50 micrograms/ml). The data indicate that the G14 mutant has been significantly and specifically affected in the expression of sugar transport activity and in the regulatory controls affecting sugar transport activity. PMID- 2108175 TI - Comparison between transport and degradation of leucine and glutamine by peripheral human lymphocytes exposed to concanavalin A. AB - Transport and pathways of leucine and glutamine degradation were evaluated in resting human peripheral lymphocytes and compared with the changes induced by concanavalin A (ConA). Cells were incubated with [1-14C]leucine (0.15 mM), [U 14C]leucine (0.15 mM), or [U-14C]glutamine (0.4 mM) after culture with or without 2, 5, 7, or 10 micrograms/ml ConA for 2, 18, or 24 hours, respectively. Initial rates of transport of leucine and glutamine were augmented 2.7-fold and threefold by the mitogen. Leucine transamination, irreversible oxidation, and catabolism beyond isovaleryl-CoA were increased by 90%, 20%, and 60%, respectively. Glutamine utilization increased threefold; accumulation of glutamate, aspartate, and ammonia increased by 700%, 50%, and 100%, respectively, and 14CO2 production by about 400% in response to ConA. The results indicate that ConA stimulates to about the same extent transport of leucine and glutamine into lymphocytes. Glutamine is mainly channeled into catabolic pathways, while leucine remains largely preserved. It is suggested that these metabolic changes provide more leucine for incorporation into protein and more N- and C-atoms required for the synthesis of macromolecules and energy from glutamine. PMID- 2108176 TI - Use of endotoxin retentive intravenous filters with paediatric total parenteral nutrition solutions. AB - We studied the retention of endotoxin released in a clinically relevant form by senescent bacteria during filtration of amino acid-based total parenteral nutrition (TPN) solutions by the PALL Intravenous Set Saver Filter (ELD96). The ELD96 was shown to be capable of providing an effluent free of detectable endotoxin (less than 0.125 endotoxin unit-equivalents/ml) when challenged with 10(6) total cells of Pseudomonas aeruginosa during simulated clinical TPN infusion. Parallel control experiments showed that endotoxin was released from the test organism and penetrated through conventional intravenous (i.v.) solution filters. PMID- 2108177 TI - Uncommon presentation of a common problem. PMID- 2108178 TI - Clinical judgment in Lyme disease. PMID- 2108179 TI - Quality of life assessment in clinical practice. PMID- 2108180 TI - Lupus nephritis: therapeutic decisions. PMID- 2108181 TI - Differential regulation of serum immunoreactive luteinizing hormone and bioactive follicle-stimulating hormone by testosterone in early pubertal boys. AB - The microheterogeneity and bioassayable activity of serum FSH (B-FSH) can be regulated by exogenous GnRH in boys with idiopathic hypogonadotropic hypogonadism and by estrogen in a women with gonadal dysgenesis, presumably via hormonally mediated changes in the degree of FSH glycosylation. To test the hypothesis that testosterone (T) regulates the circulating forms of B-FSH, we raised the serum T levels of early pubertal boys to adult levels. In this model, high dose T inhibits the pubertal nocturnal augmentation of LH secretion, apparently through decreased GnRH secretion. This model allowed us to test a second hypothesis, that B-FSH is a sensitive indicator of hypothalamic GnRH release. The boys were studied on two consecutive weekends, during which they received either saline (S) or T infusions. Beginning at noon on the study day, after an overnight acclimatization, the boys received either S or T at 33% or 100% of the adult male production rate. Blood was sampled from 2000-0800 at 10-min intervals for immunoactive LH and FSH (I-FSH) and for B-FSH, as determined by the in vitro Sertoli cell aromatase induction assay, and at 30-min intervals for T. Gonadotropin levels were analyzed as mean hourly or 3-h concentrations and as pulse profiles by two established objective peak detection programs, Cluster and Detect. During S treatment, mean LH increased after the onset of sleep (P = 0.0006) and, after plateauing for several hours, declined to baseline in the early morning hours. Mean levels of B-FSH were also minimally (but significantly) increased after the onset of sleep (P = 0.046) and paralleled the decline noted for LH. Mean levels of I-FSH did not demonstrate a diurnal rhythm. The effect of T was gonadotropin specific. High dose T abolished the nocturnal elevation in mean LH concentrations, but had no effect on the nocturnal elevation of B-FSH (P less than 0.05) or on I-FSH levels. The LH pulse frequency was greatest from 2300 0450 h, during S treatment (P = 0.016). The pulse frequency of B-FSH was also minimally increased after the onset of sleep (P = 0.045). The T infusion abolished the nocturnal increase in LH pulse frequency, without an effect on B FSH pulse frequency. B-FSH pulse frequency exceeded LH pulse frequency during S treatment (8.0 +/- 0.7 pulses/12 h vs. 5.5 +/- 0.4), and B-FSH pulses persisted throughout the night. The pulse amplitudes of LH and B-FSH were not affected by T.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2108182 TI - Thyroid function and treatment in premenstrual syndrome. AB - In 1986 it was reported that a high percentage of women with premenstrual syndrome (PMS) were found to have thyroid hypofunction (TH), mostly subclinical hypothyroidism, as defined by an augmented response of TSH to TRH, and that all affected women had complete relief of PMS symptoms with L-T4 therapy. We studied baseline thyroid function (T4, T3 uptake, T3, TSH, and TSH response to TRH) in 15 normal women (group 1) and 44 women with PMS and treated 22 of the PMS women with L-T4 (group 2; 1.6 micrograms L-T4/kg dose) and the other half with placebo (group 3) for 2 months in a double blinded protocol. We found no evidence of thyroid dysfunction in group 2 or 3, except for 1 subject with slightly elevated TSH (6.2 microIU/mL) and moderate augmented response to TRH (change in TSH, 65 microIU/mL). During the treatment phase we found a complete relief of symptoms in 6 (27%), a partial relief of symptoms in 6 (27%), and some relief of symptoms in 12 (54%) in group 2. Whereas in group 3, 10 (45%) had complete relief, 5 (23%) had partial relief, and 15 (68%) had some relief of symptoms. These results show that 1) there is no significant thyroid disease in PMS; and 2) L-T4 is no better than placebo in treatment of PMS. We conclude that the high incidence of thyroid hypofunction previously reported in PMS is due to an unusually low TSH level for the limit of the normal range for the TRH stimulation test. PMID- 2108183 TI - Peripheral glucose metabolism in human hyperthyroidism. AB - The present study was designed to determine the effect of spontaneous hyperthyroidism on the forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Ten normal subjects and 11 hyperthyroid patients were studied after an overnight fast (12-14 h) and for 3 h after ingestion of 75 g glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Increased forearm glucose uptake was observed in the hyperthyroid patients compared to that in the normal subjects (1286 +/- 212 vs. 677 +/- 88 mumol/100 mL forearm.3 h) with enhanced glucose oxidation (443 +/- 40 vs. 147 +/- 29 mumol/100 mL forearm.3 h). Nonoxidative glucose metabolism was also greater in hyperthyroid patients than in normal subjects (842 +/- 234 vs. 529 +/- 90 mumol/100 mL forearm.3 h). Basal serum FFA levels were significantly higher in hyperthyroid than in normal subjects (0.252 +/- 0.025 vs. 0.182 +/- 0.022 g/L), as were the basal lipid oxidation rates in the forearm muscles of the thyrotoxic individuals (0.290 +/- 0.066 vs. 0.088 +/- 0.016 mg/100 mL forearm.min). After glucose ingestion, serum FFA levels and lipid oxidation rates declined significantly to equivalent values in both groups of subjects, and the similar basal insulin concentrations increased to significantly higher levels in the hyperthyroid patients. In conclusion, spontaneous human hyperthyroidism increases glucose uptake by the forearm muscles in the postabsorptive state and during an oral glucose challenge, with augmented fluxes of glucose through the oxidative and nonoxidative pathways. PMID- 2108184 TI - The effects of lipoxygenase products on progesterone and prostaglandin production by human corpora lutea. AB - The present study was undertaken to assess the effects of the products of the lipoxygenase pathway on steroidogenesis and the production of prostaglandins (PGs) by human corpora lutea in the midluteal phase. In the first experiment luteal cells were cultured with 5-hydroxyeicosatetraenoic acid (5-HETE) at 10, 100, 500, or 1000 ng/mL in the presence or absence of hCG at 100 ng/mL for 10 days. The addition of 5-HETE dose-dependently inhibited progesterone (P) production by the cultural luteal cells. P production stimulated by exposure to hCG was also reduced significantly in response to 5-HETE. However, 5-HETE had no effect on the production of 6-keto-PGF1 alpha, PGF2 alpha, or PGE2 by cultured luteal cells at any point during the culture period. In the second experiment the reaction products of soybean lipoxidase of arachidonic acid (AA-LIP) were added to cultured luteal cells. Treatment with either AA or LIP alone had no effect on basal P production. The addition of AA-LIP at all concentrations tested reduced P production by cultured luteal cells in the presence or absence of hCG. AA-LIP significantly reduced basal 6-keto-PGF1 alpha secretion in cultured luteal cells on day 2. Although the stimulatory effect of AA on luteal PGE2 production was maintained throughout the entire culture period, the lipoxygenase products of AA did not affect AA-stimulated PGE2 production by cultured luteal cell. These results suggest that the products of the lipoxygenase pathway may be important in the involution of human corpora lutea. PMID- 2108185 TI - The effects of insulin and insulin-like growth factors-I and -II on estradiol production by granulosa cells of polycystic ovaries. AB - The objective of this work was to examine the effects of insulin-like growth factors (IGFs) on estradiol (E2) production by granulosa cells obtained from ovaries of patients with polycystic ovary disease (PCO). Granulosa cells, isolated from ovaries of three PCO patients, were cultured in serum-free medium containing either androstenedione alone (10(-7) M) or androstenedione plus graded doses of FSH, IGF-I, IGF-II, and/or insulin. At the end of the culture period (2, 4, or 6 days) E2 levels in the medium were measured by RIA. The results from each patient were similar, and therefore, the data were pooled. In the 6-day time course experiments, the control (untreated) cells produced relatively high levels of E2 at 2 days; however, none was detected thereafter. Treatment with FSH (30 ng/mL) stimulated E2 production 4-fold at 2 days, but the stimulatory effects of FSH were not sustained during culture. IGF-I at 30 ng/mL mimicked the effects of FSH. Concomitant treatment with FSH and IGF-I caused synergistic increases in E2 production (3-, 13-, and 33-fold at 2, 4, and 6 days, respectively). Dose response studies revealed that FSH and IGF-I stimulated E2 production in a dose dependent fashion (ED50 of FSH and IGF-I, were 1.1 +/- 0.3 and 7.6 +/- 7.2 ng/mL, respectively). In the presence of a maximally effective dose of FSH (30 ng/mL), the cells appeared to become more responsive to IGF-I (ED50 of IGF-I plus FSH, 1.09 +/- 0.29 ng/mL); however, this effect was not significant (P = 0.086). In the presence of a maximally effective dose of IGF-I (30 ng/mL), the stimulatory effect of FSH on E2 production was dramatically amplified, but the IGF-I did not significantly (P = 0.85) change the potency of FSH (ED50 of FSH plus IGF-I, 1.07 +/- 2.3 ng/mL). Treatment with IGF-II over the concentration range of 0.1-100 ng/mL had no effect on either control or FSH-stimulated E2 production. Treatment with insulin, either alone or together with FSH, increased the levels of E2, but the insulin effects were seen only at the highest doses tested (0.3-10 micrograms/mL). The results in these in vitro experiments with PCO granulosa cells indicate that 1) physiological concentrations of IGF-I are as effective as FSH in stimulating E2 production; 2) IGF-I and FSH act synergistically to control the level of E2 production; and 3) this synergy was not observed with insulin or IGF-II. PMID- 2108186 TI - Plasma glucose and free fatty acids modulate the secretion of growth hormone, but not prolactin, in the rhesus and Java monkey. AB - In 11 freely moving rhesus and 5 Java monkeys the plasma GH, PRL, and cortisol responses to suppression and elevation of plasma glucose and FFA concentrations were studied. Blood was sampled and infusions given via chronic jugular catheters, extended via a swivel into the adjacent room. In the rhesus monkeys, the mean plasma GH concentration rose during insulin-induced hypoglycemia from 4.7 +/- 1.9 to 17.4 +/- 2.5 micrograms/L at 60 min (P less than 0.001), and the mean plasma cortisol concentration from 320 +/- 55 to 700 +/- 133 nmol/L at 90 min (P less than 0.001). The mean plasma PRL concentration (basal value, 5 +/- 2.3 micrograms/L) did not change significantly. During glucose-induced hyperglycemia, the mean plasma GH concentration oscillated between 2.0-5.2 micrograms/L from 60-360 min (no significant change). Large GH secretory episodes occurred during hyperglycemia in individual animals. During nicotinic acid induced plasma FFA suppression, the mean plasma GH concentration increased from 3.7 +/- 0.6 to 17.9 +/- 2.3 micrograms/L at 270 min (P less than 0.001). During lipid-induced plasma FFA elevation, the mean plasma GH concentration decreased consistently from 6.5 +/- 1.0 micrograms/L to values between 1.3 +/- 0.2 and 2.6 +/- 0.6 micrograms/L from 60-360 min (P less than 0.01). Plasma PRL and cortisol concentrations were not affected by plasma FFA changes. Compared with the spontaneous plasma GH pattern in a previously studied group of rhesus monkeys, the mean plasma GH concentration was increased during hypoglycemia and plasma FFA suppression. It was strongly suppressed during plasma FFA elevation and slightly suppressed during hyperglycemia. Similar effects were observed in the Java monkeys, although hyperglycemia tests were not performed. We conclude the following. 1) In rhesus and Java monkeys, as in man, GH secretion is stimulated by plasma FFA suppression and is inhibited by plasma FFA elevation. In both species, acute hypoglycemia stimulates the secretion of GH and cortisol. 2) These nonhuman primates differ from man in that hyperglycemia only weakly inhibits GH secretion in the rhesus monkey, if at all (Java monkeys had no hyperglycemia tests), and in neither species does acute hypoglycemia stimulate the secretion of PRL. 3) Both primate species can serve as models for the metabolic modulation of GH secretion in man, although a suppressive effect of hyperglycemia remains to be proven. PMID- 2108187 TI - Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. AB - The acute GH release stimulated by the synthetic hexapeptide, His-DTrp-Ala-Trp DPhe-Lys-NH2 [GH releasing peptide (GHRP)], was determined in 18 normal men and compared with the effects of GH-releasing hormone, GHRH-(1-44)-NH2. Specificity of effect was assessed by measurement of serum PRL, LH, TSH, and cortisol. GHRP was administered at doses of 0.1, 0.3, and 1.0 microgram/kg by iv bolus. GHRH at a dose of 1.0 microgram/kg was administered alone and together with various does of GHRP. No adverse clinical effects of laboratory abnormalities were observed in response to GHRP. A side-effect of mild facial flushing of 1- to 3-min duration occurred in 16 of the 18 subjects who received GHRH-(1-44)-NH2. Mean (+/- SEM) peak serum GH levels after injection of placebo and 0.1, 0.3, and 1.0 microgram/kg GHRP were 1.2 +/- 0.3, 7.6 +/- 2.5, 16.5 +/- 4.1, and 68.7 +/- 15.5 micrograms/L, respectively. The submaximal dosages of 0.1 and 0.3 microgram/kg GHRP plus 1 microgram/kg GHRH stimulated GH release synergistically. Serum PRL and cortisol levels rose about 2-fold above basal levels only at the 1 microgram/kg dose of GHRP, and there were no changes in serum LH and TSH over the first hour after administration of the peptide(s). GHRP is a potent secretagogue of GH in normal men. Since GHRP and GHRH together stimulate GH release synergistically, these results suggest that GHRP and GHRH act independently. This supports our hypothesis that the GH-releasing activity of GHRP reflects a new physiological system in need of further characterization in animals and man. PMID- 2108188 TI - Transforming growth factors type beta 1 and beta 2 suppress rat astrocyte autoantigen presentation and antagonize hyperinduction of class II major histocompatibility complex antigen expression by interferon-gamma and tumor necrosis factor-alpha. AB - The transforming growth factors (TGF) type beta 1 and beta 2 are regulatory cytokines strongly affecting rat astrocyte immune functions. Both cytokines suppressed presentation of autoantigen by astrocytes: highly encephalitogenic T cells cocultured with TGF-beta-treated astrocytes in the presence of myelin basic protein did not become activated to transfer experimental allergic encephalomyelitis, a central nervous system (CNS) autoimmune disease. Furthermore, TGF-beta 1 and -beta 2 antagonized hyperinduction of astrocyte major histocompatibility complex (MHC) class II antigen expression by interferon-gamma and tumor necrosis factor-alpha. Thus, TGF-beta might be a potential regulator of CNS inflammation. PMID- 2108189 TI - Glucose-induced microvascular functional changes in nondiabetic rats are stereospecific and are prevented by an aldose reductase inhibitor. AB - Exposure of skin chamber granulation tissue vessels in nondiabetic rats to 11 or 15 mM D-glucose (but not L-glucose or 3-O-methylglucose) twice daily for 10 d induces vascular functional changes (increased albumin permeation and blood flow) identical to those in animals with mild or severe streptozotocin diabetes, respectively. These vascular changes are strongly linked to increased metabolism of glucose via the sorbitol pathway and are independent of nonenzymatic glycosylation as well as systemic metabolic and hormonal imbalances associated with the diabetic milieu. (J. Clin. Invest. 1990. 85:1167-1172.) PMID- 2108191 TI - Effect of haemolysate preparation on measurement of red cell folate by a radioisotopic method. AB - The effects of varying the method of preparation of haemolysates on the measurement of red cell folate concentration were investigated using the Simultrac kit. The concentration of ascorbic acid did not have any significant effect on the assayed concentrations of folate, but lower concentrations were obtained when the incubation time was increased. Folate was stable for 14 days in cells when they were stored at 4 degrees C and for seven days at -25 degrees C, but instability was increased by storage in ascorbic acid, by the use of stored (4 degrees C) ascorbic acid, and by preparing the haemolysates by freeze-thaw cycling. It is recommended that haemolysates should be diluted in fresh ascorbic acid, at a concentration of 10 g/l, incubated for 60 minutes in the dark and stored at -20 degrees/25 degrees C before being assayed. PMID- 2108190 TI - Immunochemical analysis of uridine diphosphate-glucuronosyltransferase in four patients with the Crigler-Najjar syndrome type I. AB - The functional heterogeneity of uridine diphosphate-glucuronosyltransferase (UDPGT) and its deficiency in human liver were investigated. The monoclonal antibody (MAb) WP1, which inhibits bilirubin and phenol-glucuronidating activity, was used to immunopurify UDPGTs from human liver. Purified UDPGTs were injected into mice to obtain new MAbs. Immunoblotting of microsomes with MAb HEB7 revealed at least three polypeptides in liver (56, 54, and 53 kD) and one in kidney (54 kD). In liver microsomes from four patients (A, B, C, and D) with Crigler-Najjar syndrome type I (CN type I), UDPGT activity towards bilirubin was undetectable (A, B, C, and D) and activity towards phenolic compounds and 5-hydroxytryptamine either reduced (A and B) or normal (C and D). UDPGT activity toward steroids was normal. Immunoblot studies revealed that the monoclonal antibody WP1 recognized two polypeptides (56 and 54 kD) in liver microsomes from patient A and none in patient B. With HEB7 no immunoreactive polypeptides were seen in these two patients. Patient C showed a normal banding pattern and in patient D only the 53 kD band showed decreased intensity. These findings suggest considerable heterogeneity with regard to the expression of UDPGT isoenzymes among CN type I patients. PMID- 2108192 TI - Evaluation of Serodia Myco II particle agglutination test for detecting Mycoplasma pneumoniae antibody: comparison with mu-capture ELISA and indirect immunofluorescence. AB - The Serodia Myco II particle agglutination test, which the manufacturers claim exclusively detects IgM antibody, was compared with two IgM-specific tests, a mu capture ELISA, and indirect immunofluorescence for their ability to detect recent Mycoplasma pneumoniae infection. In general there was good agreement among the three tests, all three having similar sensitivity. One hundred and nine (78%) of serum samples gave concordant results in all three assays. Several sera gave positive particle agglutination titres, however, while being negative by the two other assays, and the Serodia Myco II test may not be as specific for detecting M pneumoniae IgM as the other two tests. While the Serodia Myco II test may be a good screening assay, it is unlikely to be a definitive test for M pneumoniae IgM, but may be better than the complement fixation test, particularly in younger patients in whom M pneumoniae IgM is found more frequently. PMID- 2108193 TI - Intestinal microsporidiosis in AIDS. PMID- 2108194 TI - Synapsin I-like immunoreactivity in nerve fibers associated with lingual taste buds of the rat. AB - Immunoreactivity to synapsin I, a neuronal phosphoprotein, was localized in free floating tissue sections prepared from lingual tissue of rats. Many nerve fibers within the tissue exhibited clear immunoreactivity including motor endplates on striated muscle, autonomic fibers innervating blood vessels or glands, and sensory fibers innervating muscles or the lingual epithelium including taste buds. Numerous immunoreactive fibers occurred within each taste bud, with fewer, fine fibers being dispersed in the epithelium between taste buds. The majority of the intragemmal immunoreactive fibers extended throughout the taste buds most of the distance outward from the basal lamina toward the surface of the epithelium. Fine, perigemmal fibers reached nearly to the epithelial surface. Ultrastructural analysis of the immunoreactive sensory fibers revealed that synapsin I immunoreactivity occurred diffusely throughout the cytoplasm, and heavily in association with microvesicles. The synaptic vesicles at the taste receptor cell to-afferent fiber synapse were, however, not immunoreactive for synapsin I, although these vesicles fall into the size class shown to be immunoreactive in other systems. This absence of synapsin I may be a common property of vesicles in axonless short receptor cells. PMID- 2108195 TI - Segmental neurofibromatosis: immunocytochemical analysis of cutaneous lesions. AB - Cutaneous lesions from three patients with segmental neurofibromatosis were evaluated. Routine histologic studies revealed the presence of redimentary neural structures within an abundant collagenous matrix. The majority of the cells in all three cases expressed S-100 protein, suggesting their identity as Schwann cells. The stromal component stained positively for fibronectin and type IV collagen; the latter indicated the presence of basement membrane material. Embedded in the tumor mass were glandular epithelial structures that stained with epithelial membrane antigen antibody. Staining for factor VIII-related antigen revealed vascular endothelium and multiple scattered mast cells. In one case strands of cells stained with antibodies to desmin, suggesting muscle cell differentiation. This case may represent a distinct subset of neurofibromas. PMID- 2108196 TI - Effect of hCG or hCG+ treatments in young thalassemic patients with hypogonadotropic hypogonadism. AB - Hypogonadotropic hypogonadism (HH) is common (40%) in beta-thalassemic patients. Taking into consideration that in HH non-thalassemic patients we obtained good results in pubertal development using hCG treatment (1500 IU every 6 days), 10 HH thalassemic subjects (14 5/12 -17 yr, all with bone age greater than 13 6/12) were treated with the same regimen. In 5 of these patients purified FSH (75 IU every 3 days) was added to hCG in order to evaluate the FSH effect on testosterone (T) response (Group 1 was given hCG alone, Group 2 hCG + FSH: Profasi HP and Metrodin Serono). To evaluate the kinetics of testosterone response, plasma level of T was determined basally and 1, 2, 4 and 6 days after hCG injection. This dynamic study and a clinical examination were carried out at the beginning of treatment and at the 4th and 12th month after. Results obtained in the first group confirmed our previous data from non-thalassemic HH patients: in fact, after 12 months of therapy a stage G2-G3 was reached. In the second group, however, testis size and testosterone secretion were significantly higher than in the first group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108198 TI - Differences in health care spending across countries: statistical evidence. AB - The empirical evidence available for OECD countries suggests that economic factors play a major role and that demographic factors play a minor role in explaining differences in health care spending across countries. When countries are grouped on the basis of their health care systems, some significant cross country differences result: countries with higher transfer rates (a larger share of collective financing) are not generally characterized by higher health care expenditures, and conversely, countries with a larger share of private financing (including higher coinsurance rates) do not have lower expenditures. Rather, the opposite holds true. Similar conclusions apply to the share of public versus private production of health goods. Furthermore, the results do not support the claims of those critics of universal public insurance systems who consider the expansion of the coverage to be a major source of expenditure growth. These findings cast serious doubt on the claim that cost containment can be achieved via market reforms that rely heavily on direct consumer payments and cost sharing as instruments of financing. A comparative analysis of the historic record of the United States, Canada, and the Federal Republic of Germany generally supports these conclusions; it also suggests that a greater degree of public penetration offers a better chance for control of health spending, particularly in periods of austerity. There is a strong presumption that health care systems relying on some overall control of spending generally are more cost-effective than those relying more on decentralized mechanisms of control. Services are more equitably distributed in relation to health and payment for health services is far more progressive in the former type of system. PMID- 2108199 TI - Tension, compression, and shear: directions, stresses, and outcomes of health care cost control. AB - "Control" of health care costs is often portrayed as a struggle between external, "natural" forces pushing costs up and individuals, groups, and societies trying to resist the inevitable. This picture is false. Control includes strenuous efforts by some to raise costs, and by others to resist those increases, and/or to transfer costs to someone else. But all such forces originate in the purposes and interests of individuals and groups. Health care cost control is a struggle among conflicting interests over the priorities of a society, and claims of "inevitability" are simply part of the political rhetoric of that struggle. International experience supports certain conclusions. First, there is no basis for the claim that limits on expenditure growth must threaten the health of (some members of) a society. Second, there is a substantial variety of experience with cost control. Failure in the United States is often presented as evidence of the impossibility of control, but most other countries have succeeded. Finally, control requires the direct confrontation of interests, with substantial build-up of stress. Advocates of expansion are more successful if they can transform compressive forces into efforts to shift the burden onto someone else. Pressures from providers in every country for "privatization" and/or payment by users reflect this recognition of economic interest. PMID- 2108197 TI - TRH raises cytosolic Ca2+ in human adenomatous lactotrophs. AB - The effect of TRH on cytosolic free calcium concentrations, [Ca2+]i, was evaluated on cell suspensions obtained from 6 human PRL secreting pituitary adenomas. In these cells resting [Ca2+]i levels were variable (mean +/- SE; 103.8 +/- 6.5, n = 25); the addition of 100 nM TRH caused a marked [Ca2+]i rise within 20 sec., the peak values ranging from 200 to 437 nM (285 +/- 10.8 nM, n = 10). The transients induced by TRH were composed by a rapid increase, due to mobilization of calcium from intracellular stores, followed within a few seconds by a lower plateau which was due to stimulated influx from the extracellular space. In fact, when EGTA and verapamil were applied after TRH they caused the Ca2+ plateau to dissipate rapidly. The addition of 1 microM dopamine (DA) caused a substantial decrease of resting [Ca2+]i (about 10-30%) as well as an inhibition of the plateau phase induced by TRH. The effect of DA completely depended on extracellular Ca2+. The TRH-induced transients observed in adenomatous cells were quite similar in size and time course to those recorded in normal rat lactotrophs. As previously observed in rat lactotrophs, in adenomatous cells treatment with pertussis toxin (PTx, 1 microgram/ml for 4 h) was unable to affect the [Ca2+]i transients induced by TRH while completely abolished the effect of DA. The effects of TRH on in vivo and in vitro PRL secretion were also evaluated. Before surgery, no patient showed a positive response to the iv administration of 200 micrograms TRH (serum PRL levels: 95 +/- 62 ng/ml in basal conditions vs 124 +/- 92 after TRH, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108200 TI - American political culture and the search for lessons from abroad. AB - The American health care system appears to suffer from higher costs and less access than the health care systems of other industrialized nations. This perception has set social scientists searching for "lessons from abroad." This paper places the dialogue about health system lessons within the context of American political culture. It sketches out some of the distinctive dynamics in the American policymaking process. Those dynamics help explain the problems we face, the programs we have pursued, and the alternatives we have foregone. The same political process which shaped past policies is likely to frame any lessons we try to import from abroad. PMID- 2108201 TI - Retrenchment or realignment? U.S. mental health policy and DRGs. AB - The introduction of DRGs for financing health care is dramatically changing the system of delivery and provision in the U.S. To understand the consequences, it is important to focus not only on cost-containment issues but also on new institutional mechanisms fashioned to reshape health care delivery and provision. A realignment among the major actors is occurring, with the state adopting a central role in redefining its own function in the health care system, constructing a new framework and agenda for change, and enlisting the participation of other social actors in implementing change. The specific features of this realignment are analyzed in the context of mental health DRGs. This article concludes that, based on the consequences of DRGs to date, we ought to look beyond present indicators of retrenchment in the health care system to how the unique features of the American welfare state are continuing to evolve. PMID- 2108202 TI - Physician payment and cost-containment strategies in West Germany: suggestions for Medicare reform. AB - The West German health care system pays ambulatory care physicians on a fee-for service basis but employs a national relative value scale and regional capitation based revenue pools to achieve expenditure controls on total physician reimbursement. Physician-controlled organizations manage these pools and conduct utilization reviews on their own members. The capitation rates are determined by negotiations between the physician associations and health insurers. The West German government has been able to exert some influence on the outcome of these negotiations through a quasi-governmental advisory body. Aspects of this structure could be adopted by Medicare in order to determine conversion factors for resource-based relative value scales or to create expenditure control and incentive structures for Medicare-participating physicians. PMID- 2108203 TI - Simultaneous detection of different mRNA sequences coding for neuropeptide hormones by double in situ hybridization using FITC- and biotin-labeled oligonucleotides. AB - Oligonucleotides labeled with FITC or biotin were applied for detection of specific mRNAs in microscopic preparations by in situ hybridization. The oligonucleotides were labeled with one FITC or biotin molecule at the 5' end or with a tail of biotin molecules at the 3' end. The target sequences were mRNAs coding for an ovulation hormone (CDCH) in the caudodorsal cells (CDC) of the pond snail Lymnaea stagnalis and a molluscan insulin-like peptide (MIP) in the light green cells (LGC) of the same organism. The hybridized oligonucleotides were detected either directly after the hybridization procedure by fluorescence microscopy or indirectly after an immunocytochemical procedure to visualize the biotin or FITC moiety. The results indicate that the detectability of the mRNA sequences is at least partially dependent on the accessibility of the target sequences for the immunocytochemical detection systems. The positive hybridization results obtained with oligonucleotides containing different labels enabled us to perform double hybridization experiments for simultaneous detection of CDCH and MIP mRNAs in one tissue section. Using FITC- and biotin-labeled oligonucleotides, we also demonstrated simultaneously different sequences on the same mRNA molecule. PMID- 2108204 TI - Immunohistological optimization of detection of bromodeoxyuridine-labeled cells in decalcified tissue. AB - Mice were injected with a range of bromodeoxyuridine (BrdU) concentrations from 0.01 mg to 10 mg, and their jaws were fixed in buffered formalin or modified Carnoy. After EDTA or formic acid decalcification, a range of DNA denaturation schedules was assessed and immunohistological detection of BrdU-containing nuclei was performed using the Sera Lab anti-BrdU antibody MAS 250b. For Carnoy-fixed tissue, denaturation in 1 N HCl for 8 min at 60 degrees C was capable of adequately detecting an injected dose of 0.05 mg but not a dose of 0.01 mg BrdU, whereas pepsin/HCl treatment gave only weak staining after injection of 1 mg BrdU. In comparison, formalin fixation required pre-treatment with 0.2-0.4% pepsin/HCl at 37 degrees C for comparable staining intensity, but could still not adequately detect a dose of 0.1 mg BrdU. There was little detectable difference in staining between EDTA- and formic acid-decalcified tissues after injection of 10 mg BrdU. PMID- 2108205 TI - IgG1 and IgG2a production by autoimmune B cells treated in vitro with IL-4 and IFN-gamma. AB - Autoimmune MRL-lpr/lpr and NZB/W mice spontaneously secrete large quantities of pathogenic IgG1 and IgG2a autoantibodies. NZB mice also produce autoantibodies but these tend to be of the IgM H chain class. This work examines whether differences in the isotype of autoantibody produced by lupus-prone mice reflects differences in the sensitivity of autoreactive B cells to lymphokine-mediated IgG secretion. Twenty-five percent of normal BALB/c B cells produced IgG1 when stimulated in vitro with IL-4 plus LPS. This was comparable with the effect of IL 4 on small resting B cells from MRL-lpr/lpr and NZB/W mice. In contrast, less than 8% of the resting B cells from NZB mice produced IgG1 under these conditions. LPS plus IFN-gamma induced 5% of BALB/c and NZB/W but only 1% of NZB B cells to secrete IgG2a. Because lymphocytes from both young and old NZB mice showed diminished IgG1 and IgG2a secretion after lymphokine treatment, B cells from this strain appeared to be intrinsically resistant to the effects of IL-4 and IFN-gamma. In contrast, a disproportionately large proportion (22%) of B cells from adult MRL-lpr/lpr mice produced IgG2a when treated with IFN-gamma in vitro. Only B cells from MRL-lpr/lpr mice with active disease responded with such high levels of IgG2a production: cells from animals that had not yet developed clinical disease produced normal levels of IgG2a. Within each strain, B cells producing antibodies against autoantigens such as DNA, bromelain-treated mouse RBC and Sm responded to treatment with IL-4 and IFN-gamma in a manner indistinguishable from B cells producing antibodies against conventional Ag such as TNP and ARS. PMID- 2108206 TI - A monoclonal antibody that detects a novel antigen on endothelial cells that is induced by tumor necrosis factor, IL-1, or lipopolysaccharide. AB - The alteration in the surface of endothelial cells (EC) in response to cytokines is likely to be of great importance to the regulation of cell migration and thereby to the evolution of inflammatory processes. We have generated three mAb against cytokine inducible Ag on EC. Whereas mAb 1.2B6 and 6.5B5 were found to react with ELAM-1 and ICAM-1, respectively, mAb 1.4C3 reacted with a novel molecule that showed a different pattern of expression from ELAM-1 or ICAM-1 after stimulation of EC by TNF, IL-1, or LPS. Like ELAM-1, the 1.4C3 Ag was minimally expressed on resting EC, whereas ICAM-1 was moderately expressed. After stimulation with IL-1, TNF, or LPS, ELAM-1 expression was maximal after 4 to 6 h, 1.4C3 Ag after 6 to 10 h, and ICAM-1 after 10 to 24 h. The duration of 1.4C3 expression was intermediate between ELAM-1 and ICAM-1, and was more prolonged in response to TNF than IL-1 or LPS. Whereas the expression of the three Ag showed a similar dose response to varying concentrations of IL-1 or LPS, EC required a 10 fold higher concentration of TNF for half maximal expression of ELAM-1 than for half maximal expression of 1.4C3 Ag or ICAM-1 (5 ng/ml compared to 0.5 ng/ml). Of the three Ag, only ICAM-1 was enhanced by IFN-gamma. SDS-PAGE under reducing conditions showed the 1.4C3 Ag to migrate as a single band with a relative molecular mass of approximately 95 kDa. mAb 1.4C3 adds to our understanding of the kinetics of the EC response to different cytokines and will be useful in studying the regulation of EC activation. Furthermore, the 1.4C3 molecule may have an important role in leukocyte-EC interactions. PMID- 2108207 TI - A role for cytokines in antigen presentation: IL-1 and IL-4 induce accessory functions of antigen-presenting cells. AB - Fixation of APC with 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide (ECDI) eliminates their ability to stimulate proliferation of alloreactive T cells or the D10 T cell clone, although a partial response, IL-4 production, was measured. However, if APC were activated before fixation, they could be ECDI-fixed and retain the ability to induce T cell proliferation. IL-1, IL-4 or LPS were capable of activating APC in this way, whereas IFN-gamma was not. This activation step occurred in 6 h, required protein synthesis, and was distinct from increases in Ia or IL-1. This suggests resting APC lack structures that are essential for inducing T cell proliferation. PMID- 2108208 TI - Diverse VH and VL genes are used to produce antibodies against a defined protein epitope. AB - mAb secreting hybridomas were produced from mice hyperimmune to the model Ag tobacco mosaic virus protein. Six mAb were selected for their ability to bind synthetic peptides corresponding to amino acid residues 103-112 and 97-107 of tobacco mosaic virus protein. These mAb were analyzed for their fine specificity by measuring binding to synthetic analogs of the decapeptide, and cDNA sequences encoding the mAb V regions were determined. These analyses revealed that a wide range of different V regions are capable of binding with the same decapeptide epitope, and that these antibody sequence differences generally coincided with different binding fine specificities. This diverse antibody response with specificity for the same epitope demonstrates both the breadth of potential of the immune system and the lack of exclusivity in specific protein:protein interactions. PMID- 2108209 TI - Kinetics of phospholipase A2, arachidonic acid, and eicosanoid appearance in mouse zymosan peritonitis. AB - Intraperitoneal injection of zymosan into mice induces a peritonitis characterized by cellular influx, plasma leakage and the appearance of arachidonic acid (AA) metabolites. We report that zymosan injection also stimulates the accumulation of AA, docosahexaenoic acid, linoleic acid, and phospholipase A2 (PLA2) activity. The amount of the unsaturated fatty acids (UnFA) varies both with the zymosan dose and time. Significantly increased levels of UnFA were first detected 15 min after zymosan injection. Maximal levels of the UnFA were reached 1 to 2 h post zymosan injection (AA: 725 +/- 29 ng/mouse, docosahexaenoic acid: 296 +/- 23 ng/mouse, linoleic acid: 4489 +/- 179 ng/mouse) and declined to saline control levels by 8 h. PLA2 activity was significantly increased 5 to 15 min after zymosan injection. Maximal levels of PLA2 activity occurred 15 to 30 min after zymosan injection (31.8 +/- 9.1 nmol phospholipid/mg protein/h) and then decreased by 30% through 24 h. Neither the appearance of UnFA nor PLA2 activity correlated with cellular influx, but both were coincident with plasma exudation at 5 to 15 min after zymosan. However, maximal exudation occurred 1 to 2 h post zymosan injection similar to that seen with the UnFA but not PLA2. These latter results suggest that a significant portion of the UnFA found in the peritoneal cavity of zymosan-injected mice originates from the plasma. PLA2 activity at the early time points (5 to 15 min) may also contribute to the levels of UnFA via hydrolysis of tissue and/or cellular phospholipids. PMID- 2108210 TI - Evidence for 5-lipoxygenase activity in human B cell lines. A possible role for arachidonic acid metabolites during B cell signal transduction. AB - Ligand binding to B lymphocytes via membrane Ig initiates a cascade of events beginning with the hydrolysis of phosphatidylinositol 4,5-bisphosphate into diacylglycerol and inositol 1,4,5-trisphosphate. Subsequent to the activation of protein kinase C and the induction of a rise in intracellular calcium by diacylglycerol and inositol 1,4,5-trisphosphate, there is gene transcription and eventually cellular activation. By mimicking the initial event of B cell activation with phorbol ester and calcium ionophore one can begin to identify the many mediators used in signaling between the membrane and the nucleus. We have examined the effect of calcium on arachidonic acid (AA) metabolism in several EBV transformed human B cell lines. The cells were labelled with [3H]AA and stimulated with the calcium ionophore A23187. Analysis of the supernatant by reversed-phase HPLC demonstrated a dose-dependent release of an AA metabolite that coeluted with authentic 5-hydroxyeicosatetraenoic acid (5-HETE). In addition, the AA metabolite coeluted with standard 5-HETE under straight-phase chromatography. Further analysis by RIA confirmed the identification of 5-HETE and revealed an additional metabolite, 5-HETE lactone (5-HL). 5-HL is the intramolecular ester of 5-HETE generated in the presence of acid. We were unable to convert [3H] 5-HETE into 5-HL during sample preparation unless cells were present, suggesting that the 5-HL, is of cellular origin. These results suggest that the AA metabolites 5-HETE and its intramolecular ester 5-HL may play a role in B cell activation because they are produced subsequent to a rise in intracellular Ca2+, an event that occurs during cross-linking of membrane Ig. PMID- 2108211 TI - Neutrophil activation by inflammatory microcrystals of monosodium urate monohydrate utilizes pertussis toxin-insensitive and -sensitive pathways. AB - The activation of leukocytes by particulates is a critical event in certain inflammatory syndromes, including acute gout associated with microcrystals of monosodium urate monohydrate. In this study we have evaluated mechanisms of human neutrophil activation by urate crystals. Both N-formyl-nor-leu-leu-phe-nor-leu tyr-lys and uncoated urate crystals (0.5 to 5 mg/ml) but not urate crystals coated with human low density lipoprotein (which suppresses crystal-induced neutrophil responsiveness), stimulated pertussis toxin (PT)-sensitive GTPase activity in purified preparations of human neutrophil membranes. Hydroxyapatite crystals (up to 5 mg/ml) were inactive. Pretreatment of neutrophil membranes with cholera toxin also inhibited crystal-induced and formylated peptide-induced GTPase activity. Pretreatment of whole neutrophils with PT resulted in nearly complete inhibition of formylated peptide-induced cytosolic calcium mobilization, release of superoxide and release of the azurophil granule constituent alpha mannosidase. In contrast, identical pretreatment of whole neutrophils with PT only partially suppressed urate crystal-induced alpha-mannosidase and superoxide release and failed to inhibit crystal phagocytosis and increases in cytosolic free calcium. Mechanisms of neutrophil activation by monosodium urate crystals appear to be heterogeneous in comparison with activation by formylated peptides and there is no absolute requirement for PT-sensitive membrane G proteins in neutrophil responsiveness to urate crystals. PMID- 2108212 TI - Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. AB - We have examined the receptor-ligand interactions and the method of phagocytosis of virulent Mycobacterium tuberculosis by human monocytes. mAb against complement receptors (CR) inhibit adherence and phagocytosis of M. tuberculosis in fresh nonimmune serum. A mAb against the type 1 CR (CR1) inhibits adherence of M. tuberculosis by 40 +/- 5%, and three different mAb against the type 3 CR (CR3) each inhibit adherence by 39 +/- 5% to 47 +/- 4%. A mAb against CR1 used in combination with one of the three mAb against CR3 inhibits adherence by up to 64 +/- 7%. Most strikingly, two mAb used in combination against CR3 inhibit adherence by up to 81 +/- 2%. mAb against other monocyte surface Ag do not significantly influence adherence. In like fashion, mAb against CR but not other monocyte surface Ag inhibit adherence of preopsonized M. tuberculosis in the presence of heat-inactivated serum. By electron microscopy, monocytes ingest all M. tuberculosis that adhere in the presence of nonimmune serum; mAb against CR3 markedly inhibit ingestion. In contrast to CR, the FcR and the beta-glucan inhibitable receptor for zymosan play little or no role in mediating M. tuberculosis adherence or ingestion. Adherence of M. tuberculosis is serum dependent, requiring greater than or equal to 2.5% serum for optimal adherence. Heat inactivation of serum markedly reduces adherence of M. tuberculosis (75.5 +/ 7%) and preopsonization of bacteria enhances adherence by 2.9 +/- 0.4-fold. Adherence is also markedly reduced in C3- or factor B-depleted serum; repletion with C3 or factor B increases adherence by 2.1 +/- 0.4-fold and 1.86 +/- 0.05 fold, respectively. Fab anti-C3 IgG markedly inhibits monocyte adherence of preopsonized M. tuberculosis (71 +/- 1%). C component C3 is fixed to M. tuberculosis by the alternative C pathway as determined by a whole bacterial cell ELISA. Human monocytes ingest M. tuberculosis by conventional phagocytosis as viewed by electron microscopy. This study demonstrates that human monocyte CR1 and CR3 mediate phagocytosis of M. tuberculosis and C component C3 in serum is acting as the major bacterium-bound ligand. PMID- 2108213 TI - V region gene usage and somatic mutation in the primary and secondary responses to influenza virus hemagglutinin. AB - Most (80 to 90%) primary antibodies specific for the Sb site of influenza virus (A/PR/8/34) hemagglutinin share an Id (designated C4). Secondary antihemagglutinin(Sb) antibodies also exhibit the C4 Id although less frequently (10 to 15%). We have analyzed the V region nucleotide sequences of primary and secondary antibodies with the C4 Id. Primary C4 antibodies are encoded by the same Vk gene, belonging to the Vk8 group, usually rearranged to Jk5. The H chains are diverse, encoded by VH genes belonging to at least four different VH families, a variety of DH genes, and either JH2, JH3, or JH4. There is only one somatic mutation among seven Vk and two VH genes encoding primary C4 antibodies. Secondary C4 antibodies are also encoded by the same Vk8-Jk5 gene segment and by diverse VH genes. Additional heterogeneity in the secondary response is caused by somatic mutation. PMID- 2108215 TI - Mouse V lambda x gene sequence generates no junctional diversity and is conserved in mammalian species. AB - The lambda x, a new mouse Ig lambda L chain, is produced by rearrangement of the V lambda x, J lambda 2, and C lambda 2 gene segments. The V lambda x amino acid sequence is as divergent to other V lambda as to Vk gene sequences. Additionally, its third hypervariable region (CDR3) is four amino acids longer than those of all other variable gene segments of murine L chain. We have cloned and sequenced the germ-line V lambda x gene and found that the unexpected CDR3 length is encoded by the V lambda x gene. Junctional diversity is prevented by a TAA termination codon localized at the V lambda x 3' extremity. Moreover, we show a striking conservation of the V lambda x sequence in various mammalian species. Portions of the V lambda x sequence display more than 70% of nucleotide sequence identity with rabbit and human variable regions. These results suggest that V lambda x predated the divergence of mammalian species. PMID- 2108214 TI - Myelomas and lymphomas expressing the Ig gamma 2a H chain gene have similar transcription termination regions. AB - During B cell differentiation, the membrane and secretion specific forms of the Ig gamma-H chains of mouse are differentially expressed as a function of the developmental stage of the cell. Representatives of less differentiated and memory B cells (lymphomas) that have undergone the class switch to gamma 2a or gamma 2b H chains produce nearly equal amounts of membrane specific (gamma m) vs secretory specific (gamma s) mRNA. Fully differentiated gamma 2a or gamma 2b plasma cells and their tumors, myelomas, switch to higher levels of gamma s mRNA production relative to gamma m. Selective use of either the gamma s poly(A) site or the downstream gamma m poly(A) site accompanied by specific splicing events could modulate production of these two forms of mature gamma H chain mRNA. Alternatively, transcription termination could be modulated. Through a combination of hybrid protection and in vitro nascent RNA analyses of transcripts from gamma H chain-producing cells arrested at various stages of development, we have mapped transcription termination in both lymphomas (gamma s approximately gamma m mRNA) and in myelomas (gamma s much greater than gamma m) mRNA. Regardless of the developmental stage of the cell, transcription proceeds at a significant level through both the secretory- and membrane-specific poly(A) sites and terminates at least 500 nucleotides downstream of the gamma m poly(A) site in both the gamma 2a and gamma 2b genes. We conclude that transcription termination does not play a major role in the switch to elevated levels of gamma s production in late stage gamma-producing myeloma cells and that alternative RNA processing alone must be responsible for the differential expression of the gamma H chain mRNA. PMID- 2108216 TI - Nucleotide sequence of a human monoclonal anti-idiotypic antibody specific for a rabies virus-neutralizing monoclonal idiotypic antibody reveals extensive somatic variability suggestive of an antigen-driven immune response. AB - We previously described the isolation and characterization of a human monoclonal anti-idiotypic antibody (Ab2) isolated from EBV-transformed human PBL after immunization with rabies vaccine. The present study concerns the molecular characteristics of the Ab2 and the germ-line elements that gave rise to it. The H chain of this antibody derives from the small VHV family of human V region gene segments. Parallel studies on the germ-line VHV gene isolated from the same individual revealed that the expressed molecule contains 19 nucleotide differences in the VH gene segment. The D segment of Ab2 could have arisen by a D to D fusion; the J segment is a JH6. Extensive somatic variation evident in the H chain variable region of this naturally arising monoclonal anti-idiotypic antibody suggests that this Ab2, the product of a CD5+ B cells, was the consequence of an Ag-driven immune response. PMID- 2108217 TI - Effects of treatment with IL-2 receptor specific monoclonal antibody in mice. PMID- 2108218 TI - A modified colorimetric assay of macrophage activation for intracellular cytotoxicity against Leishmania parasites. AB - An in vitro method is described which colorimetrically assesses the activation of macrophages for intracellular cytotoxicity against the obligate intracellular parasite Leishmania donovani. The assay system uses a highly purified macrophage population derived from 10-day murine bone marrow cultures. These were infected in vitro as a suspension culture with viable L. donovani amastigotes and then exposed to activating agents. After 48 h the intracellular parasites were released by SDS lysis of the macrophages. Surviving Leishmania organisms were quantitated by their conversion of the chromophore MTT. The sensitivity of this method was comparable with the established method of [3H]dThd incorporation. This assay system has been used to show that there is a dual signal requirement (recombinant interferon-gamma and bacterial endotoxin (LPS] for effective activation of macrophages for leishmanicidal activity. PMID- 2108219 TI - A new sensitive assay for measurement of cell-mediated cytotoxicity to intact layers of cultured human keratinocytes. AB - A cytotoxicity assay for sensitive measurement of cell-mediated lympholysis (CML) of human cultured keratinocytes (cK) is described. The usage of 51Cr-labeled keratinocytes in intact layers as target cells in this assay allows objective and accurate determination of lysis of keratinocytes which have not undergone trypsin and suspension-induced membrane changes. Furthermore, the problem of high spontaneous 51Cr release values encountered with suspended keratinocytes is overcome. The assay was applied to study antigen-specific CML of cK by cloned cytotoxic T cells (CTL) and to determine the effect of IFN-gamma on the susceptibility of cK to lysis. The results showed that HLA-A2 specific CTLs could reproducibly lyse cK of HLA-A2 positive healthy skin donors both with and without incubation of cK with IFN-gamma. Applications of this keratinocyte cytotoxicity assay lie in determining the antigenic expression of human cK, in analysis of effector cell/keratinocyte interactions in CML and of the modulatory effects of cytokines on these mechanisms. The assay thus may provide a helpful tool in gaining insight into the role of CML of keratinocytes in the destruction of inflamed skin. PMID- 2108220 TI - Measurement of cytokine release by human cells. A quantitative analysis at the single cell level using the reverse haemolytic plaque assay. AB - The reverse haemolytic plaque assay has been adapted to detect and measure the release of such cytokines as interleukin-1, -2 and -6, GM colony-stimulating factor or interferon-gamma by individual human cells derived from either peripheral blood or enzymatically dispersed breast carcinomas. Since each of these peptides is released by more than one cell type, this in vitro assay has been coupled with immunocytochemistry to identify the particular cell type(s) contributing to the release of each cytokine. This technique is useful in (i) obviating the need for purification of a given cell type prior to estimating cytokine release, and (ii) evaluating quantitative differences in secretion amongst cells of a particular type. Such a method has the additional advantage over most alternative methods applied at the single cell level in that the cells remain viable at the end of the assay and can be used in further studies. This assay thus provides a powerful new tool in the investigation of the role of cytokines in both the normal modulation of the immune system and the development of such diseases as neoplasia. PMID- 2108221 TI - Measurement of macrophage adherence and spreading with weak electric fields. AB - A new method to monitor macrophage attachment on protein-coated surfaces and spreading in response to activating agents is described. Murine macrophages were cultured on small gold electrodes coated with protein, and attachment and spreading were detected as electrical impedance changes. The rate of attachment of cells to fibronectin-coated electrodes was measured to be significantly greater than to other proteins tested. Activation agents used included interferon gamma, lipopolysaccharide and heat killed Listeria monocytogenes. Addition of each agent to macrophages on electrodes resulted in characteristic patterns in the impedance time course with impedance changes as large as 40%. PMID- 2108222 TI - Detective work in continuous ambulatory peritoneal dialysis. AB - We report five cases of continuous ambulatory peritoneal dialysis in which the mechanisms and sources of infection were established. We show how diligent enquiry and environmental investigation can explain the pathogenesis of infection and help in prevention by motivation of the patient. PMID- 2108223 TI - Response of nuclear polyhedrosis virus-resistant Spodoptera frugiperda larvae to other pathogens and to chemical insecticides. AB - Selection in the laboratory for Spodoptera frugiperda (Sf) resistant to nuclear polyhedrosis virus (NPV) affected the susceptibility of the insect to certain other mortality agents, including a chemical insecticide. Median lethal concentrations (LC50S) and associated statistics were compared for several mortality agents between colonies of NPV-resistant and -susceptible (control) insects. Compared to the susceptible insects, the NPV-resistant insects were cross-resistant to the S. frugiperda granulosis virus and to the Autographa californica NPV based on nonoverlap of 95% fiducial limits of the LC50S. The NPV resistant insects were significantly more susceptible to methyl parathion than the control insects. The two colonies of S. frugiperda did not differ significantly in their response to Bacillus thuringiensis, Vairimorpha necatrix, or carbaryl. The cross-resistance experiments were based on per os exposure of the insects to the pathogens and insecticides; the susceptibility of the resistant and control insects did not differ significantly when the Sf NPV was injected into the hemocoel or when methyl parathion was applied topically. PMID- 2108224 TI - New molecular techniques for microbial epidemiology and the diagnosis of infectious diseases. AB - A major aim of clinical microbiologists over the last century has been to demonstrate the presence of pathogenic microorganisms in clinical or pathologic samples associated with infectious diseases. With the development of molecular genetics over the last two decades, new technologies have become available that allow more sensitive and specific determinations to be made in shorter periods. Two considerable benefits have accrued: Epidemiologists are now capable of judging clonality among various clinical isolates more powerfully, permitting added accuracy in the evaluation of the epidemic spread of microbes, and clinicians have gained enormous ability to diagnose previously difficult-to detect pathogens. PMID- 2108225 TI - Diagnosis of acute typhus infection using the polymerase chain reaction. AB - The first use of the polymerase chain reaction (PCR) for the diagnosis of an acute rickettsial infection is described. A primer pair derived from the 17-kDa antigen sequence of Rickettsia rickettsii gave specific amplification of a 434 base pair DNA fragment from the genome of Rocky Mountain spotted fever and endemic and epidemic typhus. The assay could detect as few as 30 rickettsiae. Detection of PCR-amplified DNA with a nonradioactive DNA probe confirmed an acute infection with Rickettsia prowazekii. PMID- 2108226 TI - Route-related variation in immunogenicity of mycobacteria. AB - The route of immunization was observed to play a significant role in deciding the T-cell response to immunization with killed mycobacterial vaccines. Slow-growing mycobacteria were found to be immunogenic by both the intraperitoneal (i.p.) and intradermal (i.d.) routes; rapid-growing mycobacteria were immunogenic by the i.d. route only. The nonresponder state following i.p. immunization with Mycobacterium vaccae could be corrected by treatment of the mice with poly I:poly C or indomethacin prior to immunization. Both poly I:poly C, an interferon inducer, and indomethacin, a prostaglandin inhibitor, are known to enhance the expression of major histocompatibility complex glycoproteins. Since they are so important in antigen preparation, it was concluded that the inability of mice to respond to M. vaccae by the i.p. route is likely due to defective presentation of the bacterial antigens by the antigen-presenting cells at the site, namely, the peritoneal macrophages. These findings are significant because M. leprae has been reported to be antigenically similar to M. vaccae, and the response of mice to i.p. immunization with both of these mycobacteria is very similar. PMID- 2108227 TI - Hepatocyte modulation of Kupffer cell prostaglandin E2 production in vitro. AB - It is likely that dynamic interactions between hepatocytes and Kupffer cells contribute to the responses of these cell types both under normal conditions and during sepsis. In this study, we examined the influences of hepatocytes on the concentration of the inflammatory mediator PGE2 in Kupffer cell cultures. Evidence to suggest that cultured rat hepatocytes both metabolize PGE2 and produce a substance that promotes LPS-stimulated Kupffer cell PGE2 biosynthesis include the following: 1) PGE2 levels in Kupffer cell: hepatocyte coculture were lower than the levels in Kupffer cell cultures early after LPS stimulation; 2) 36 h after LPS, coculture PGE2 levels exceeded the levels in Kupffer cell cultures despite the demonstrated capacity for hepatocytes to metabolize PGE2; 3) a transferable, non-dialyzable, and heat-unstable factor in hepatocyte supernatant promoted PGE2 production when added to Kupffer cells with LPS or after LPS; 4) there was no increased PGE2 synthesis when the hepatocyte supernatant was added without LPS or if hepatocyte supernatant was preincubated with the Kupffer cells for 6 or 18 h before LPS administration; 5) there was an inability of the hepatocyte factor to promote PGE2 production in response to other macrophage activating agents, including calcium ionophore A23187 or phorphol myristate acetate; and 6) there was no increased cell replication or protein synthesis in the Kupffer cell cultures following hepatocyte supernatant incubation. The increased Kupffer cell PGE2 production by the hepatocyte supernatant was not due to contamination of the hepatocyte supernatant by endotoxin or PGE2. These in vitro results raise the possibility that hepatocytes have the capacity to modulate local PGE2 levels by two distinct mechanisms. Hepatocytes can metabolize PGE2 as well as release factor(s) which promote LPS-induced PGE2 production by Kupffer cells. PMID- 2108228 TI - In vivo and in vitro assessment of porcine neutrophil activation responses to chemoattractants: flow cytometric evidence for the selective absence of formyl peptide receptors. AB - Interest in the role that activated granulocytes play in C5a-induced myocardial ischemia prompted us to investigate and compare activation responses of pig and human neutrophils. The responses of Hypaque-Ficoll purified porcine (P-PMN) and human neutrophils (H-PMN) to stimulation with N-formyl-methionyl-leucyl phenylalanine (FMLP), C5a, phorbol myristate acetate (PMA), and calcium ionophore A23187 (A23187) were compared by flow cytometrically measured changes in the cells' forward (FWD-SC) (a measure of shape/volume change) and right angle (90 degrees-SC) light scatter (a measure of secretion), and in the distribution of the membrane potential sensitive fluorescent probe di-O-C (3). FMLP, C5a, and Zymosan-activated serum (ZAS stimulated chemotaxis and FMLP vs. PMA-stimulated adherence to plastic were also compared. Unstimulated P-PMN had lower FWD-SC and 90 degrees-SC than H-PMN (39.4 +/- 1.4 vs. 48.4 +/- 2.0 P less than 0.05, and 32.7 +/- 2.7 vs. 52.4 +/- 1.5 units, P less than 0.005, for FWD-SC and 90 degrees SC of P-PMN vs. H-PMN, respectively). P-PMN selectively failed to increase their FWD-SC upon stimulation with FMLP (0.0 +/- 0.5% vs. 26.1 +/- 6.8%, P-PMN vs. H PMN), or decrease their 90 degrees-SC when treated with cytochalasin B + FMLP (secretion) (2.4 +/- 0.1% vs. -35.8 +/- 4.6% change in 90 degrees-SC, P-PMN vs. H PMN), while responding comparably to C5a, PMA, and A23187. P-PMN failed to depolarize in response to FMLP but responded similarly to H-PMN when activated by C5a, A23187, and PMA. P-PMN's chemotactic response to FMLP was selectively absent since the cells responded well to purified pig C5a. FMLP stimulated significant increases in H-PMN adherence to bovine serum albumin-coated plastic (44.1 +/- 6.7% vs. 12.6 +/- 3.7%, FMLP vs. buffer, P less than 0.025), but failed to increase adherence of P-PMN above baseline 0.68 +/- 0.20% vs. 2.12 +/- 1.90%, FMLP vs. buffer, P greater than 0.05. PMA (100 ng/ml) stimulated comparable increases in adherence in both PMN types (48.6 +/- 5.2% vs. 58.7 +/- 4.9%, P-PMN vs. H-PMN, P less than 0.025). Binding studies using the fluoresceinated N-formyl peptide f-met-leu-phe-lysine-fluorescein-isothiocyanate (FMLPL-FITC) in the absence and presence of excess non-fluoresceinated FMLPL indicated that P-PMN lack specific binding sites for the N-formyl peptides.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2108229 TI - Immunolocalization of G protein alpha-subunits in the Drosophila CNS. AB - In order to uncover the role of G proteins in the integrative functioning and development of the nervous system, we have begun a multidisciplinary study of the G proteins present in the fruit fly, Drosophila melanogaster. In this report, we describe the distribution of 3 different G protein alpha-subunits in the adult Drosophila CNS as determined by immunocytochemical localization using affinity purified antibodies generated to synthetic oligopeptide sequences unique to each alpha-subunit. Western blot analysis of membranes prepared from Drosophila heads indicates that antibodies specific for the Drosophila Go alpha and Gs alpha homologs recognize the appropriate protein species predicted by molecular cloning (Quan et al., 1989; Thambi et al., 1989). The Gi alpha homolog could not be detected in head membranes by Western blotting, consistent with the negligible levels of expression observed for Gi alpha on Northern blots of head mRNA (Provost et al., 1988). However, a Drosophila Gi alpha fusion protein could be detected by these antibodies following expression in E. coli. Immunolocalization studies revealed that the Go alpha and Gs alpha homologs are expressed at highest levels in neuropils and at intermediate levels in the cortex of all brain and thoracic ganglion areas. Only the lamina contained low levels of these alpha subunits in the CNS. Additionally, Gs alpha appears to be associated with the cell membranes of neuronal cell bodies, while Go alpha has a more diffuse distribution, suggesting its presence in the cytoplasm as well as cell membranes. In contrast to the wide distribution of Go alpha and Gs alpha, Gi alpha has a surprisingly restricted distribution in the CNS. It is present at high levels only in photoreceptor cell terminations, glomerulae of the antennal lobes, and the ocellar retina. Little or no Gi alpha was detected in other brain regions or in the thoracic ganglion. Gi alpha, then, appears to be uniquely associated with some primary sensory afferents and their terminations, suggesting the presence of specific receptor and/or effector systems which mediate the transmission of primary sensory information in Drosophila. PMID- 2108230 TI - Differential expression of two neuronal intermediate-filament proteins, peripherin and the low-molecular-mass neurofilament protein (NF-L), during the development of the rat. AB - The expression of peripherin, an intermediate filament protein, had been shown by biochemical methods to be localized in the neurons of the PNS. Using immunohistochemical methods, we analyzed this expression more extensively during the development of the rat and compared it with that of the low-molecular-mass neurofilament protein (NF-L), which is expressed in every neuron of the CNS and PNS. The immunoreactivity of NF-L is first apparent at the 25-somite stage (about 11 d) in the ventral horn of the spinal medulla and in the posterior part of the rhombencephalon. The immunoreactivity of peripherin appears subsequently, first colocalized with that of NF-L. Both immunoreactivities then spread out along rostral and caudal directions, but whereas the immunoreactivity of NF-L finally becomes noticeable in every part of the nervous system, that of peripherin remains localized to (1) the motoneurons of the ventral horn of the spinal medulla; (2) the autonomic ganglionic and preganglionic neurons; and (3) the sensory neurons. These results demonstrate that, in the neurons that originate from migrating neural crest cells, the immunoreactivities of peripherin and of NF L become apparent only when they have reached their destination. The results also show that peripherin is expressed more widely than has been previously observed and that this protein occurs in neuronal populations from different lineages (neural tube, neural crest, placodes) with different functions (motoneurons, sensory and autonomic neurons). The common point of these neurons is that they all have axons lying, at least partly, at the outside of the axis constituted by the encephalon and the spinal medulla; this suggests that peripherin might play a role in the recognition of the axonal pathway through the intermediary of membrane proteins. PMID- 2108231 TI - The organization and connections of somatosensory cortex in marmosets. AB - Microelectrode mapping methods were used to define and describe 3 representations of the body surface in somatosensory cortex of marmosets: S-I proper or area 3b of anterior parietal cortex, S-II, and the parietal ventral area (PV) of the upper bank of the lateral sulcus. In the same animals, injections of anatomical tracers were placed into electrophysiologically determined sites in area 3b or S II. Mapping results and patterns of connections were later related to architectonic fields that were delimited in sections cut parallel to the surface of manually flattened cortex and stained for myelin. There were several major results. (1) Recordings from area 3b revealed a characteristic somatotopic organization of foot to face in a mediolateral sequence as previously reported in other members of the marmoset family (Carlson et al., 1986). (2) Multiple injections of WGA-HRP in area 3b demonstrated dense, patchy interconnections with ipsilateral S-II, PV, area 3a, and area 1, less dense interconnections with primary motor cortex (M-I), the supplementary motor area (SMA), limbic cortex of the medial wall (L), and rostrolateral parietal cortex of the lateral sulcus (PR), and callosal connections with areas 3b, S-II, and PV. Injections of 3 different tracers into the representation of 3 body regions in area 3b indicated that the connections with areas 3a, 3b, 1, S-II, and PV are topographically organized. (3) Recordings from cortex on the upper bank of the lateral sulcus demonstrated a somatotopic representation of the body surface that matches that of S-II of other mammals. S-II immediately adjoined areas 3b along the dorsal lip of the lateral sulcus. The face representation in S-II was adjacent to the face representation in 3b while the trunk, hindlimb, and forelimb were represented in a caudorostral sequence deeper in the sulcus. (4) Injections in S-II revealed ipsilateral connections with areas 3a, 3b, 1, a presumptive area 2, PV, PR, M-I, SMA, limbic cortex, the frontal eye fields, and the frontal ventral visual area. Dense callosal connections were with S-II and PV. (5) The recordings also revealed a systematic representation just rostral to S-II that has not been previously described in primates.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2108232 TI - Right ventricular assist and prostacyclin infusion for allograft failure in the presence of high pulmonary vascular resistance. AB - The presence of high pulmonary vascular resistance (PVR) greater than 4 Wood units contributes to significant early posttransplant mortality, and remains a negative predictor of long-term survival. Current trends have been toward exclusion of the recipient with high PVR from the orthotopic procedure; elective heterotopic allograft placement is increasingly advocated. A patient with a PVR of 6 Wood units underwent orthotopic transplantation; the cardiac allograft from a 12 kg heavier donor was implanted after an ischemic time of 115 minutes. Early graft failure at 4 hours and subsequent cardiac arrest were followed by reinstitution of cardiopulmonary bypass, during which time optimal pharmacologic manipulation of the pulmonary vasculature was undertaken, including the use of high-dose prostacyclin. Refractory right heart failure indicated the requirement for right ventricular assistance (RVA) for patient survival. RVA with a Bio Medicus pump was instituted in association with high-dose prostacyclin; an intraaortic balloon pump was inserted 12 hours later. Maintenance immunosuppression consisted of cyclosporine and azathioprine alone. RVA was maintained for 3 days; during this time the patient was totally pump dependent. Over an 18-hour period the patient was weaned and successfully withdrawn from RVA. Intraaortic balloon pump counterpulsation and the prostacyclin infusion were continued for 6 and 10 days, respectively. The clinical implications of the various interventions that resulted in the patient's survival are discussed. PMID- 2108233 TI - Plasma retinol-binding protein response to vitamin A administration in infants susceptible to bronchopulmonary dysplasia. AB - We hypothesized that changes in plasma retinol-binding protein (RBP) concentration in response to vitamin A administration might be useful for evaluating vitamin A status of very low birth weight infants susceptible to bronchopulmonary dysplasia. We prospectively studied 24 consecutively admitted neonates (birth weight less than 1350 gm, gestational age less than 31 weeks, ventilator dependent for greater than 24 hours after birth), who were eligible to receive 2000 IU supplemental vitamin A by intramuscular injection on postnatal day 1 and on alternate days thereafter for 28 days. In addition to serial assessment of vitamin A status, we measured plasma RBP just before and 1, 3, and 6 hours after an intramuscular injection of vitamin A (2000 IU/kg retinyl palmitate) on days 1 and 28. The percent increase in plasma RBP (delta-RBP) was high (mean +/- SD: 61 +/- 37%) and plasma vitamin A and RBP values were low on day 1, indicative of vitamin A deficiency. Supplemental vitamin A improved vitamin A status of all infants as shown by low delta-RBP (mean +/- SD: 8 +/- 9%) and normal plasma vitamin A and RBP values on day 28. Bronchopulmonary dysplasia was diagnosed in 12 of 24 infants. Infants with bronchopulmonary dysplasia had a higher mean (+/- SD) delta-RBP on day 28 than those without bronchopulmonary dysplasia (13 +/- 10% vs 3 +/- 3%, p less than 0.01), indicative of persistence of low vitamin A status in infants with lung disease despite supplementation. We conclude that the plasma RBP response to vitamin A is a useful indicator of vitamin A status in very low birth weight infants. Although vitamin A supplementation at the dosage used in this study normalizes conventional plasma indexes of vitamin A in very low birth weight infants, the plasma RBP response to vitamin A may continue to reflect persistence of low vitamin A status in the more immature infants with significant lung disease. We suggest that the plasma RBP response to vitamin A may be a useful functional test in such infants. PMID- 2108234 TI - Calcium-dependent protein phosphorylation in Babesia bovis and its role in growth regulation. AB - Intracellular growth of protozoan parasite Babesia bovis has been followed to study the effect of some chemical agents on growth regulation. Using an in vitro parasite culture system we present evidence that the normal growth of the parasite is dependent upon available calcium and a Ca2(+)-binding protein, calmodulin, because sequestration of either of these 2 components from the culture medium causes inhibition of parasitic growth. Further studies demonstrate that the parasite contains a protein kinase that can phosphorylate a 40-kDa parasitic protein and its activity is regulated by calcium and calmodulin. Both the enzyme and its substrate are present in the membrane of the parasite. In addition, the parasite also contains a highly active protein kinase C activity that is documented by phosphorylating histone, a known substrate for protein kinase C. These findings suggest a possible correlation between the growth of parasite and calcium/calmodulin-dependent protein phosphorylation activity. PMID- 2108236 TI - Continuous in vitro cultivation of Sarcocystis cruzi. AB - Sporozoites of Sarcocystis cruzi were inoculated onto monolayer cultures of bovine pulmonary artery endothelial (CPA) cells. Sporozoites entered the cells, formed large and small multinucleate schizonts, and produced large numbers of merozoites. Continuous cultivation from the original sporozoite inoculum has been maintained for more than 1,320 days by subinoculating merozoites onto new cultures of CPA cells. During this time, the capacity to produce both types of schizonts was preserved, and schizogony was the only form of reproduction that was observed. PMID- 2108235 TI - Protective qualities of mitochondrial and cytosolic fluorescent dyes against in vitro and in vivo infection by the Tulahuen strain of Trypanosoma cruzi. AB - This study demonstrates the binding of various fluorescent dyes (3,3' dihexyloxacarbocyanine iodide [DiOC6I], doxycycline [DOTC], rhodamine 123, and merocyanine 540) to infectious and intracellular forms of the Tulahuen strain of Trypanosoma cruzi. These dyes predominantly localize in mitochondria. Following treatment with DiOC6I and DOTC, both irradiated and nonirradiated samples showed dark toxicity to T. cruzi, whereas the other dyes effected toxicity only following irradiation with light. Under in vitro conditions, 91% protection was obtained 96 hr postinfection under dark conditions through the use of 0.573 micrograms/ml of DiOC6I. During in vivo studies, the onset of parasitemia was delayed by 7 days through the use of DiOC6I in ng/ml levels. Host deaths occurred in the infected control group on day 11 postexposure, whereas in the 5.7-ng/ml dye-treated group, no death had occurred after 20 days postexposure. This study demonstrates delay of onset of T. cruzi infections with the use of DiOC6I at concentrations well below the levels toxic to the host. PMID- 2108237 TI - Naturally occurring apicomplexan acute interstitial pneumonitis in thick-billed parrots (Rhynchopsitta pachyrhyncha). AB - This report describes acute interstitial pneumonitis due to an apicomplexan parasite with schizogony in endothelial cells of pulmonary vessels accompanied by early and metrocyte stages of sarcocysts in the heart of a thick-billed parrot (Rhynchopsitta pachyrhyncha). The pattern of this disease is similar to that of the acute phase (approximately 10-15 days postinoculation) of experimental infections of budgerigars, Melopsittacus undulatus, with high doses of sporocysts of Sarcocystis falcatula. PMID- 2108238 TI - A potassium channel activator modulates both excitatory noncholinergic and cholinergic neurotransmission in guinea pig airways. AB - The effect of a potassium channel activator, cromakalim (BRL 34915), on excitatory nonadrenergic noncholinergic (e-NANC) and cholinergic neural bronchoconstriction was studied in guinea pigs. We monitored airway opening pressure as an index of airway caliber. After atropine (1 mg/kg iv.) and propranolol (1 mg/kg iv.), bilateral vagal stimulation evoked an e-NANC response. Cromakalim did not alter basal airway caliber, but reduced the e-NANC response to vagal stimulation in a dose-dependent manner, with a maximal inhibition of 71.9 +/- 9.2% (mean +/- S.E.) at 400 micrograms/kg i.v. (P less than .01). Pretreatment with phentolamine (2.5 mg/kg i.v.) had no effect on the inhibitory response produced by cromakalim but glibenclamide (25 mg/kg iv.), an inhibitor of ATP-sensitive potassium channels, blocked its effect. Cromakalim had no inhibitory effect on exogenous substance P (5-25 micrograms/kg i.v.)-induced bronchoconstriction. In animals depleted of tachykinins by capsaicin (50 mg/kg s.c.) pretreatment, cromakalim had an inhibitory effect on both vagalcholinergic and exogenous acetylcholine (0.3-2 micrograms/kg i.v.)-induced bronchoconstriction, although the inhibitory effect was significantly greater on neural stimulation. We conclude that potassium channels modulate both e-NANC and cholinergic neurotransmission, and to a lesser extent acetylcholine-induced bronchoconstriction in guinea pig airways. PMID- 2108239 TI - Effects of BRL 34915 (cromakalim) on renal hemodynamics and function in anesthetized dogs. AB - The effects of BRL 34915, a newly developed potassium channel opener, on renal hemodynamics and function were investigated in anesthetized dogs. An i.v. injection of BRL 34915 (4, 20 and 100 micrograms/kg) caused a dose-related reduction of mean arterial pressure but there were no significant changes in renal blood flow. The agent at lower doses (4 and 20 micrograms/kg) produced a slight increasing action on urine formation. When BRL 34915 was infused intrarenally at nonhypotensive doses (0.04 and 0.2 micrograms/kg/min), there were no significant increases in renal blood flow and glomerular filtration rate. At 1.0 micrograms/kg/min, a dose which produced a slight reduction in mean arterial pressure, significant decreases in calculated renal vascular resistance were observed, thereby indicating that BRL 34915 has vasodilator action on the renal vasculature. In cases of infusion at higher doses (0.2 and 1.0 micrograms/kg/min), the levels of urine flow, urinary excretion of sodium and fractional excretion of sodium were elevated significantly and these events were accompanied by decreases in urine osmolality. Although the intrarenal administration of BRL 34915 at higher doses produced no alterations in the fractional excretion of lithium (index of sodium excretion at the proximal tubules), the agent did increase the calculated value of the fractional distal excretion of sodium. These effects seen when BRL 34915 was infused intrarenally were suppressed markedly by glibenclamide (6 mg/kg i.v.), a putative inhibitor of the ATP-sensitive potassium channel. Our results suggest that BRL 34915 has renal vasodilating and diuretic effects as a result of opening the potassium channels within the kidney. The agent-induced diuresis may be due partly to an inhibitory effect on sodium reabsorption at the distal portion of the tubules beyond the proximal tubules. PMID- 2108240 TI - The Na(+)-dependent release of endogenous dopamine and noradrenaline from rat brain synaptosomes. AB - The involvement of intrasynaptosomal-free Ca++ concentration [( Ca++]i) in Na(+) dependent release of endogenous dopamine and noradrenaline from rat brain synaptosomes was studied. The release of endogenous dopamine and noradrenaline from rat whole brain synaptosomes were measured using high-performance liquid chromatography with electrochemical detector. The change of [Ca++]i was measured fluorometrically using a Ca++ indicator, Quin-2. Whether extracellular Ca++ was present or not, 30 microM veratridine, a Na(+)-ionophore, increased the release of endogenous dopamine and noradrenaline. In the presence of 1.25 mM Ca++, 30 microM veratridine increased [Ca++]i. In contrast, in the absence of extracellular Ca++, veratridine did not affect [Ca++]i. Ethylene glycol bis(beta aminoethyl ether)-N,N'-tetraacetic acid (EGTA) increased the release of dopamine and noradrenaline in Ca-Mg-free medium. This stimulatory effect of EGTA seemed to be the result of an increase in the influx of Na+ through Ca++ channels in the absence of divalent cation. In Ca-Mg-free medium, EGTA caused a slight decrease in [Ca++]i. The EGTA-stimulated release of dopamine and noradrenaline was blocked by La which also significantly blocked the decrease in [Ca++]i observed after the addition of EGTA. These results suggest that the Na(+)-dependent release of dopamine and noradrenaline may not depend on a change in [Ca++]i. Veratridine (30 microM)-induced release of dopamine and noradrenaline were detected simultaneously. However, the time needed to induce the maximal stimulatory effect of veratridine on the release of dopamine was apparently shorter than that of noradrenaline. This delay might suggest that the Na(+)-dependent release process of dopamine is not similar to that of noradrenaline. PMID- 2108242 TI - New applications of lithium therapy. AB - Several placebo-controlled double-blind studies have indicated that lithium sometimes augments antidepressants, converting nonresponding patients to responders. Lithium therapy has also benefitted some schizoaffective patients and some alcoholics. Side effects are minimal. Mechanisms involved in lithium's effectiveness have not yet been discovered. PMID- 2108241 TI - G-protein-linked serotonin receptors in mouse kidney exhibit identical properties to 5-HT1b receptors in brain. AB - The serotonin 1b (5-HT1b) receptor is thought to mediate both pre- and postsynaptic actions of serotonin. Until recently 5-HT1b sites were thought to be present only in rodent brain. We now report the presence of high-affinity [125I]iodocyanopindolol [( 125I] ICYP) binding sites in the mouse renal medulla with properties identical to those of brain 5-HT1b receptors. In vitro receptor autoradiography demonstrates that [125I]ICYP binding is highly localized to the outer stripe of the renal medulla. Association and dissociation kinetics, saturation analysis and competition displacement analyses indicate that renal medullary [125I]ICYP binding sites exhibit identical properties with brain 5-HT1b receptors. Incubation of renal medullary or brain membranes with guanylimidodiphosphate results in a decreased affinity of 5-HT1b sites for 5-HT and [125I]ICYP; this can be reversed by the addition of a purified mixture of G proteins (Gi/Go). Treatment of brain or kidney membranes with N-ethylmaleimide results in a decrease in 5-HT1b binding which can also be restored by reconstitution with purified G proteins. Adenylyl cyclase from renal medullary homogenates or minces can be stimulated more than 3-fold by forskolin and attenuated by 5-HT. These results indicate that mouse kidney contains high affinity 5-HT1b receptors with identical properties to those found in brain. These are localized in the outer stripe of the renal medulla and are functionally coupled to adenylyl cyclase inhibitor (Gi) G-proteins. PMID- 2108243 TI - Cytopathic action of Naegleria fowleri amoebae on rat neuroblastoma target cells. AB - The axenically cultured, weakly pathogenic Naegleria fowleri LEE and the highly pathogenic, mouse passaged N. fowleri LEEmp are cytopathic for B103 rat nerve cells in culture. Cytopathogenicity was measured by release of radiolabeled rubidium or radiolabeled chromium from B103 target cells. Cytopathogenicity was time-dependent for up to 18 h and dependent upon amoebae effector to nerve cell target ratios of less than 1:1. Release of 51Cr from B103 cells by either LEE or LEEmp amoebae was enhanced by addition of calcium or magnesium to medium free of these divalent cations but the ion-channel inhibitor, verapamil, or the ionophore A23187 and phorbol myristate acetate did not alter release of 51Cr from B103 cells cocultured with the amoebae. Cycloheximide or actinomycin D impaired release of 51Cr from B103 target cells injured by either LEE or LEEmp amoebae. Both strains of amoebae were fractionated by glass bead disruption and high speed centrifugation into membrane and soluble fractions. Each fraction was incubated with either 86Rb or 51Cr labeled nerve cells. The membrane fraction from LEEmp was more active than the soluble fraction in facilitating rubidium and chromium release. In contrast, the soluble fraction from LEE was more active than the membrane fraction in facilitating rubidium release from radiolabeled target cells. The sequential release of 86Rb and 51Cr from target cells rather than the simultaneous release of the two isotopes indicates that target cell death is due to the release of ions followed later by the release of large macromolecules. The results indicate that N. fowleri amoebae injure nerve cells by two alternate mechanisms, trogocytosis or contact-dependent lysis. PMID- 2108244 TI - Ascogregarina saraviae n. sp. (Apicomplexa: Lecudinidae) in Lutzomyia lichyi (Diptera: Psychodidae). AB - Ascogregarina saraviae n. sp. (Apicomplexa: Lecudinidae) is described from wild caught Lutzomyia lichyi (Diptera: Psychodidae) females. Gametocysts adhered to the hemocoel side of the genital accessory gland walls and oocysts were injected into their lumina. Sporulated oocysts were ellipsoidal, 12.4 x 5.8 (11.6-13.1 x 5.6-5.9) micrometers, contained eight sporozoites and a refractile residuum. The elongate form of A. saraviae n. sp. oocysts, and their more delicate walls, clearly distinguish them from oocysts of A. chagasi (Adler & Mayrink, 1961). PMID- 2108245 TI - Association of anti-DNA idiotype markers with clinical and serological manifestations in patients with systemic lupus erythematosus. AB - Serum levels of 6 anti-DNA antibody idiotypes were measured in 65 consecutive patients with systemic lupus erythematosus (SLE) and 45 healthy subjects. Five of the 6 idiotypes were elevated in SLE sera compared to the normal controls (p less than 0.005). Analysis of the associations of the idiotypes with clinical, hematological, and serological characteristics revealed that significantly decreased serum levels of 3 idiotypes (103.1, 100, and 1305) were associated with nephritis and that one of these idiotypes (103.1) was also associated with discoid rash. An association of lowered levels of 3 idiotype markers (604, 1305, and 1400) was also observed with the presence of lupus anticoagulant and anticardiolipin antibodies. Serial studies in individual patients with SLE nephritis failed to show a close correlation of serum idiotype levels with the degree of proteinuria, creatinine clearance, anti-DNA antibody, or complement values. The association of decreased levels of specific idiotypes with the presence of nephritis, discoid rash, and antiphospholipid antibodies suggests the participation of these antibodies in the pathogenesis of disease. PMID- 2108246 TI - Clinical value of an integrated ELISA system for the detection of 6 autoantibodies (ssDNA, dsDNA, Sm, RNP/Sm, SSA, and SSB). AB - An ELISA panel assay (ANA/6) which simultaneously detects IgG autoantibodies against 6 antigens (ssDNA, dsDNA, Sm, RNP/Sm, SSA, and SSB) was evaluated with sera from 98 patients with systemic lupus erythematosus (SLE) and related conditions, 68 disease controls, who were positive or negative by fluorescent ANA (FANA), and 100 healthy controls. The antigen panel specifically identified the particular autoantibodies present and had a high level of sensitivity which was reflected by the frequency of detection of autoantibodies in different patient groups. All active patients with SLE were positive for at least one autoantibody and 80% of these patients had 3 or more autoantibodies compared to only 20% of inactive patients. A large heterogeneity in antibody profiles was also noted. About 90% of patients with positive FANA, but no detectable autoimmune rheumatic disorder, i.e., false positive, were negative by the panel. A new method of standardization was designed to use the ANA/6 quantitatively. Very large differences in the level of all 6 autoantibodies were observed between sera from patients with active and inactive SLE, suggesting a potential usefulness of ANA/6 for patient management. PMID- 2108247 TI - Low incidence of proteinuria in RA after gold thiosulfate treatment. PMID- 2108248 TI - Cardiovascular studies in the mucopolysaccharidoses. AB - Cardiovascular studies were performed on 22 patients with mucopolysaccharidosis ascertained from an epidemiological study on the mucopolysaccharidoses in Northern Ireland. None of the patients had attended a cardiologist before the study. The main echocardiographical findings were thickening of the interventricular septum and left ventricular posterior wall in the absence of ECG evidence of ventricular hypertrophy. Moreover, reduced QRS voltages were present in the majority of the patients (77%) and some had reduced shortening fraction (33%). These findings suggest an infiltrative cardiomyopathy owing to mucopolysaccharide deposition as a cause of the cardiac thickening rather than true ventricular hypertrophy. Thickening of the mitral valve was present in one case and thickening of the aortic valve in two cases. Involvement of the other heart valves was minimal and aortic valve disease was not found in any of the cases of Morquio's disease type A. In conclusion, the clinical, ECG, and chest x ray findings and echocardiographical evidence for valvular involvement were significantly less than in other studies. Hence, the incidence of clinically significant cardiovascular disease in patients with mucopolysaccharidosis has probably been overestimated. PMID- 2108249 TI - Crystallization of the Bacillus subtilis histidine-containing phosphocarrier protein HPr and of some of its site-directed mutants. AB - The histidine-containing phosphocarrier protein (HPr) from Bacillus subtilis has been crystallized. Two of the site-directed mutants aimed at probing function produce crystals suitable for X-ray studies. The mutant in which His15 is substituted by an alanyl residue crystallizes from ammonium sulfate solution in space group P3(1)21 or P3(2)21, with unit cell dimensions: a = b = 47.3 A; c = 61.5 A. These crystals diffract to at least 1.8 A resolution. The mutant in which Ser46 is substituted by an aspartyl residue crystallizes from polyethylene glycol 4000 solution in space group P2(1), with unit cell dimensions: a = 49.4 A; b = 25.6 A; c = 60.3 A; beta = 109 degrees. These crystals diffract to at least 2.0 A resolution. PMID- 2108250 TI - Crystallization of a chymotrypsin inhibitor from Erythrina caffra seeds. AB - Crystals of a chymotrypsin inhibitor from Erythrina caffra seeds have been grown out of lithium sulfate, by the hanging drop method of vapor diffusion. The crystals belong to the rhombohedral space group R32, with a = 67.2 A and alpha = 99.4 degrees, and diffract to 3 A resolution. PMID- 2108251 TI - Nature of the SOS-inducing signal in Escherichia coli. The involvement of DNA replication. AB - The SOS genes of Escherichia coli, which include many DNA repair genes, are induced by DNA damage. Although the central biochemical event in induction, activation of RecA protein through binding of single-stranded DNA and ATP to promote cleavage of the LexA repressor, is known, the cellular event that provides this activation following DNA damage has not been well understood. We provide evidence here that the major pathway of induction after damage by a typical agent, ultraviolet light, requires an active replication fork; this result supports the model that DNA replication leaves gaps where elongation stops at damage-induced lesions, and thus provides the single-stranded DNA that activates RecA protein. In order to detect quantitatively the immediate product of the inducing signal, activated RecA protein, we have designed an assay to measure the rate of disappearance of intact LexA repressor. With this assay, we have studied the early phase of the induction process. LexA cleavage is detectable within minutes after DNA damage and occurs in the absence of protein synthesis. By following the reaccumulation of LexA in the cell, we detect repair of DNA and the disappearance of the inducing signal. Using this assay, we have measured the LexA content of wild-type and various mutant cells, characterized the kinetics and conditions for development of the inducing signal after various inducing treatments and, finally, have shown the requirement for DNA replication in SOS induction by ultraviolet light. PMID- 2108252 TI - Sequential removal of Ca2+ from satellite tobacco necrosis virus. Crystal structure of two EDTA-treated forms. AB - Two forms of EDTA-treated satellite tobacco necrosis virus (STNV) have been studied with X-ray crystallography methods. The crystals of both forms were isomorphous with native STNV crystals, and (FEDTA-Fnat) maps as well as (2FEDTA Fnat) maps were calculated with phases from the native structure. The maps were based on partial data sets to 2.8 A resolution, and averaged using the 60-fold non-crystallographic symmetry. In the first crystal form, calcium ions were absent from one of the three sites in the icosahedral protein shell. The crystals were produced at pH 5.0 from a virus solution treated with EDTA at pH 6.5. The virions were not expanded, and no essential changes were seen in the protein shell. In the second crystal form, all calcium ions in the protein shell were absent. The virus material in these crystals had been subjected to treatment with EDTA at pH 8.0 before crystallization at pH 6.5. The high pH treatment caused degradation of the viral RNA. No expansion of the virion had occurred and all protein--protein contacts were retained. These results are compared with the previously presented low-resolution structure of slightly expanded STNV with intact RNA, where calcium ions from two sites were absent. The relevance of Ca2(+)-depleted virions for infection in vivo is discussed as well as the possibility that the Ca2(+)-binding sites may be parts of ion channels in the viral capsid. One possible RNA-binding site was found in the maps of both crystal types, and the same site could also be localized in the high-resolution map of native STNV. PMID- 2108253 TI - Testimony to the Pepper Commission: the United States Bipartisan Commission on Comprehensive Health Care. AB - Finally, let me emphasize that the National Medical Association stands ready to assist the Congress in structuring and implementing any new programs that may result from this gathering. We do have a concern regarding the lack of basic race specific data, including the extent of long-term care problems in the black communities. It is widely believed that an improved data base to assess the needs and to deal with the issues confronting the black and other minority or economically disadvantaged patient would greatly help to improve existing modes of treatment and outcome. PMID- 2108255 TI - Simultaneous up-regulation of neurofilament proteins during the postnatal development of the rat nervous system. AB - The expression of neurofilament (NF) proteins was examined during postnatal development of the rat nervous system in order to elucidate the nature of NF expression during the period of transition from the embryonic (immature) to the adult (mature) stages of NF expression. mRNAs to the light (NF-L), mid-sized (NF M), and heavy (NF-H) NF proteins were compared by Northern blots and by in situ hybridizations, in NF-rich (i.e., DRG, spinal cord and brainstem) and in NF-poor (i.e., cerebellum and cerebral cortex) regions of the developing rat nervous system. NF proteins were analyzed by gel electrophoresis and by immunoblots. In each tissue, the expression of NF-H was delayed compared to that of NF-L and NF M, as previously reported. The present study now shows that the delayed expression of NF-H is accompanied by parallel up-regulations in the expressions of NF-L and NF-M, both at the levels of mRNA and protein. Similar rates of increase of all three NF mRNAs occur between postnatal days 5 (P5) and 24 (P24) in rat spinal cord and DRG. Furthermore, the postnatal up-regulation of NF expression is characterized by a progressive accumulation of all three NF proteins in the tissues. The findings indicate that the adult pattern of NF expression (with high levels of expression of all three NF proteins) becomes established during the postnatal period of development, raising questions as to the nature of factors that coregulate the expression of NF subunits. PMID- 2108254 TI - A pilot double-blind study of sodium-magnesium EDTA in peripheral vascular disease. AB - Ten male patients with peripheral vascular disease, Type 2 (LaFontaine), were randomly assigned in a double-blind study to receive either Na2 ethylene diamine tetra acetic acid (EDTA) plus MgSO4, B complex, and vitamin C, or a placebo of MgSO4, B complex, and vitamin C in Ringer's lactate solution. A total of 20 intravenous infusions were planned for administration to each patient. Clinical and laboratory (noninvasive) tests showed dramatic improvements after 10 infusions in some patients, and thus was broken the code indicating who was receiving EDTA and who was receiving placebo. The group that improved had been receiving EDTA; there was no change in the placebo group. The trial was then completed in a single-blind fashion. Patients originally assigned to receive placebo then received 10 EDTA infusions, while the group originally assigned to EDTA received 20 EDTA infusions. The group that had formerly received placebo showed improvements comparable to those seen in the first EDTA group after 10 treatments. PMID- 2108256 TI - Characterization of the distinctive neurofilament subunits of the soma and axon initial segments in the squid stellate ganglion. AB - The stellate ganglion, which gives rise to the giant axons of the squid, was dissected into two parts, one containing primarily cell bodies and the other axon initial segments. A neurofilament protein-enriched extract of each was prepared and compared biochemically and immunochemically with an axoplasmic neurofilament preparation and with the glial sheath that surrounds the axons. Both parts of the ganglion lacked the 220 kDa subunit of axoplasmic neurofilaments (NFs). However, they did contain a protein of about 190 kDa that reacted with the Pruss anti intermediate filament antibody (aIFA; Pruss et al.: Cell 27:419-428, 1981), but not with a phosphorylation-dependent NF antibody (Cohen et al.: J Neurosci 7: 2056-2074, 1987). Dephosphorylation of the axoplasmic NF220 yielded a product that comigrated on two-dimensional (2D) gel electrophoresis with the 190 kDa ganglion protein, suggesting that the latter represented the incompletely phosphorylated precursor of NF220. The major low molecular weight aIFA-reactive species in the ganglion preparations was a polypeptide of about 65 kDa. A relatively small quantity of that polypeptide was also found in axoplasm and it comigrated in 2D gels with an aIFA-reactive polypeptide from the glial sheath. These results indicate that the site of modification of the 190 kDa NF precursor to the 220 kDa axonal form is probably at the point where the axon initial segments leave the ganglion, which is several mm distal to its site of synthesis in the cell body. Furthermore, the filament network of the axoplasm and possibly the cell bodies includes a glial-like intermediate filament protein in addition to the NF protein subunits. PMID- 2108257 TI - Effects of haemorrhagic septicaemia vaccination and levamisole administration on the humoral response in cross-bred calves. AB - Levamisole administered by oral, subcutaneous or transdermal routes following vaccination against Pasteurella multocida enhanced the humoral response in cross bred calves. The group that received levamisole subcutaneously elicited highly significant (P less than 0.01) antibody titres during the primary humoral response in comparison with groups that received levamisole orally or transdermally. During the secondary response in the same experiment, levamisole administered subcutaneously and transdermally showed highly significant (P less than 0.01) haemagglutination titres relative to oral administration of the drug. In a second experiment, the group that received levamisole subcutaneously showed highly significant (P less than 0.01) antibody titres during the anamnestic humoral response over other treated groups. PMID- 2108260 TI - Treatment of lead poisoning. PMID- 2108258 TI - Potential retroviral RNAs in Creutzfeldt-Jakob disease. AB - The molecular nature of the related infectious agents that cause Creutzfeldt Jakob disease (CJD) and scrapie is poorly understood, and an agent-specific nucleic acid genome has not yet been identified. Several biological manifestations of these agents resemble those seen in retrovirus-induced diseases. We therefore attempted to identify an agent-specific retrovirus-like RNA transcript in CJD infectious fractions. A series of synthetic oligonucleotides complementary to known mammalian retroviral primer binding sites were used in a primer extension assay. Substrate nucleic acids isolated from partially purified hamster brain CJD infectious fractions and from parallel normal brain fractions were compared with total starting brain RNA. This sensitive exogenous strong-stop reaction revealed that CJD infectious fractions contained a series of potential retroviral RNAs including apparent transcripts of endogenous hamster IAP genes. Most transcripts selectively recovered in the fractions were substantially protected from micrococcal nuclease digestion, and at least one substrate RNA, consistent with an intracisternal A particle, was packaged in a form that had the same buoyant density as CJD infectivity. Although a completely CJD-specific transcript was not identified, the copurification of potential retroviral transcripts with CJD infectivity suggests that models of disease involving retrovirus-like nucleic acid elements deserve further consideration. PMID- 2108259 TI - Effects of a highly basic region of human immunodeficiency virus Tat protein on nucleolar localization. AB - Human immunodeficiency virus type 1 encodes a positive trans-activator protein, Tat, which is located predominantly in the cell nucleolus. To study the role of the basic region of Tat in nucleolar localization, we constructed fusion genes encoding serially deleted segments of Tat joined to the amino-terminal end of the Escherichia coli beta-galactosidase molecule. We show that the basic region of Tat was sufficient for nuclear localization but not for nucleolar localization. Addition of three amino acids (59, 60, and 61) of the Tat sequence at the C terminal end of the basic region was necessary for the chimeric beta galactosidase to localize in the nucleus as well as in the nucleolus. We demonstrate that a short amino acid sequence (G-48 RKKRRQRRRA HQ N-61), when fused to the amino terminus of beta-galactosidase, can act as a nucleolar localization signal. PMID- 2108262 TI - Pulse oximetry. PMID- 2108261 TI - The effect of independent practice association plans on use of pediatric ambulatory medical care in one group practice. AB - We compared the use of pediatric ambulatory medical care of 640 children who switched from a traditional Blue Cross plan to more comprehensive independent practice association plans with that of matched patients who remained with Blue Cross in one large, suburban pediatric practice in Rochester, NY. A quasi experimental, retrospective cohort design was used. Use of pediatric ambulatory medical care by patients in the independent practice association plan and control patients was determined by medical chart review for 1 year before and 1 year after each patient's switch. During the baseline year, patients who would join the independent practice association plan already had 19% more acute-illness visits than control patients. During the second year, patients in the independent practice association plan averaged 42% more acute-illness visits, 22% more well child-care visits, 93% more chronic-illness visits, 27% more after-hours visits, 53% more weekend visits, 185% more laboratory studies, and 70% more referrals. The shift toward independent practice association plans in this open-market setting increased use of ambulatory medical care for pediatric patients. PMID- 2108263 TI - IgA nephropathy in Pakistan. AB - A light, electron and immunofluorescence microscopy study was performed on 102 consecutive patients on whom suitable percutaneous renal biopsies were obtained. In this selected group of patients primary IgA glomerulonephritis was diagnosed in 6 (5.9%) cases. On light microscopy the glomerular lesions were predominantly focal (WHO class III) and diffuse mesangial proliferative glomerulonephritis (Class IV). The mesangial deposits showed high association with IgM deposits and presence of early complement components (C1q, C4) indicative of both classical and alternative pathways of C3 activation in our patients. The high incidence of nephrotic syndrome with microhaematuria (5 cases) is due to patient selection when compared to other studies. This study shows the existence of IgA nephropathy in Pakistan and larger number of cases need to be investigated to determine the true prevalence of this disease and its clinical manifestations and importance in Pakistan. PMID- 2108264 TI - Evaluation of nutritional status and its effects on morbidity and mortality of surgical patients. AB - Sixtynine patients (31 males and 38 females) above the age of 12 years undergoing surgery under general anaesthesia were selected for this study. Thirty percent males and 29% females were depleted, 55% and 37% males and females, respectively, were normal and 13% and 34% males and females, respectively, were obese as indicated by Body-mass index (BMI). Measurement of midarm-muscle-circumference (MAMC) indicated mild to moderate protein deficiency in 32% of the patients while triceps skinfold thickness (T.S.T) indicates mild to severe calorie deficiency in 68% males and 50% females. Dietary intake both pre and post operatively was unsatisfactory. Pre-operatively 26% of the females had Hb level below normal (less than 11 G%). Only 3-5% of the patients had protein and albumin level below normal (less than 3.5 G%). Post-operatively all the anthropometric measurements as well as serum protein and albumin levels decreased and BUN increased significantly indicating body catabolism. Post operative hospital stay was significantly more in undernourished patients. PMID- 2108265 TI - A study of the use of atracurium in minor and major surgery. AB - Seventy patients were administered Atracurium, during six months from November, 1986 to April, 1987, for muscle relaxation during minor to major surgery. Age range was between 16-75 years with an average of 45. No premedication was used. Induction was with 2.5%, Sodium Pentothal and maintenance with gas, oxygen and halothane. Sixty one (87%) patients had good surgical relaxation. Two (2.85%) adequate and seven (10%) had poor relaxation. Major complications were bradycardia, eleven (15.7%) patients and bronchospasm (12.8%) nine patients. Sixty three (90%) had spontaneous recovery. Atracurium was found to be a safe muscle relaxant with an added advantage of elimination by Hoffman's reaction. PMID- 2108266 TI - Pathophysiology of gastroesophageal reflux: a collective review. PMID- 2108267 TI - Squamous cell carcinoma of the lung in a dry battery worker. PMID- 2108269 TI - Bashir's mother's syndrome. PMID- 2108268 TI - Malignant melanoma of the heel. PMID- 2108270 TI - Basic statistics in medical practice. PMID- 2108271 TI - [Enhancement of mononuclear leukocyte-mediated anti-tumoral activity by cells of the B cell-line]. AB - Cytotoxic activity of human mononuclear leukocytes (MNLs) against various tumor cell-line cells was induced by irradiated B cell-line cells. Each B cell-line cell was found to have a different potentiality and time kinetics on the induction of cytotoxicity. The enhancing effect of some B cell-line cells was found to be related to the IL-2 production from the MNLs, but not related to the IFN, TNF, and LT production. An analysis of the effector cells of the B cell activating-killer cells (BAK) indicated that the population of the major effector cells were monocytes and NK cells. These results have provided evidence that B cell-line cells are capable of enhancing nonspecific cytotoxic activity of the MNLs, and that they might be new biological response modifiers of cancer immunotherapy. PMID- 2108273 TI - Hyperglycemia, ketosis and mild metabolic acidosis in two patients subsequently found not to require insulin. PMID- 2108272 TI - Natural killer and lymphokine-activated killer activities in stomach cancer patients with special emphasis on the effect of 5-fluorouracil, adriamycin and mitomycin-C chemotherapy. AB - The cytotoxicities of peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells were studied to evaluate the effect of chemotherapy on cellular immunity, in 18 patients with unresectable stomach cancer before and after chemotherapy with 5-fluorouracil, adriamycin and mitomycin-C (FAM), and in 21 healthy volunteers. LAK cells were generated in vitro by culturing PBL with 100 U recombinant human interleukin-2 (rH-IL-2)/ml for 72 h. K562 (human myelogenous leukemia), MKN-45 (human stomach adenocarcinoma) and PC-14 (human pulmonary adenocarcinoma) were used as target cells. The cytotoxicity of PBL to K562 and MKN-45 was suppressed in patients with stomach cancer before chemotherapy, compared with that in healthy volunteers (P less than 0.05). The cytotoxicity of LAK cells was significantly higher to all three cell lines tested than that of PBL in both the healthy volunteers and stomach cancer patients (P less than 0.01); however, a lower level of LAK activity was generated in patients with cancer compared to that in the healthy volunteers. FAM therapy did not suppress the cytotoxicities of PBL and LAK cells. The surface markers of PBL and LAK cells were measured, demonstrating that there was no significant change in the percentage of lymphocytes with CD3+, CD4+, CD8+, CD16+ or CD19+ after chemotherapy. The ratios of CD4+ to CD8+ cells in PBL and LAK cells were also not significantly changed after chemotherapy. In the present study, we have demonstrated that the PBL of stomach cancer were defective in generating LAK activity compared to those of controls, but the LAK activity generated from PBL receiving chemotherapy was similar to that from PBL without chemotherapy in stomach cancer patients. PMID- 2108274 TI - [Documentation system for enterostomy therapy]. PMID- 2108275 TI - [Caring for patients with rheumatism close to their residence--problems and attempts at resolution from a nursing viewpoint]. PMID- 2108276 TI - [Reintegration courses for nurses. Pilot project by the German Federation of Nurses, county association Baden-Wurttemberg]. PMID- 2108277 TI - [Nursing and handling of completely implantable catheter systems]. PMID- 2108278 TI - [Risks in handling cytostatic drugs?]. PMID- 2108279 TI - [Dealing with the dying]. PMID- 2108280 TI - [Visit to a nursing school in Middle England]. PMID- 2108281 TI - [Psychiatric nursing in the future]. PMID- 2108282 TI - Prophylactic therapy for rejection after cardiac transplantation. A comparison of rabbit antithymocyte globulin and OKT3. AB - The value of prophylactic monoclonal or polyclonal antibody therapy early after cardiac transplantation is controversial. Between Jan. 1, 1987, and July 1, 1988, 32 consecutive patients underwent cardiac transplantation (cyclosporine, azathioprine, and prednisone maintenance therapy) with either early prophylactic rabbit antithymocyte globulin (n = 17) or monoclonal OKT3 (Ortho Diagnostic Systems, Inc., Raritan, N.J.) (10 days) (n = 15). Follow-up was through Sept. 1, 1988, for morbid events and through Jan. 1, 1989, for survival. All patients (100%) survived the study period (follow-up of 6 to 24 months). The efficacy of rabbit antithymocyte globulin and OKT3 prophylaxis was similar regarding median time (days) to first rejection (16 versus 21 days, p = 0.5), number of rejection episodes during first 2 months (1.5 versus 1.3 days, p = 0.8), and freedom from rejection at 2 months (18% versus 27%, p = 0.8). Early infections were slightly less common in the rabbit antithymocyte globulin group than the OKT3 group (median time to first infection: 318 versus 250 days, p = 0.5; freedom from rejection at 2 months: 82% versus 64%, p = 0.21), although differences were likely due to chance. Cytomegalovirus syndrome was common, with one case of cytomegalovirus pneumonia. T-cell markers during OKT3 treatment did not predict subsequent rejection (within 2 weeks after OKT3) as assessed by mean T3 lymphocyte count during OKT3 use (p = 0.3) or T3-lymphocyte count during the last 3 days of OKT3 use (p = 0.4). Inferences: (1) Prophylactic rabbit antithymocyte globulin or OKT3 with triple-drug immunosuppression yields excellent intermediate survival after heart transplantation. (2) These protocols for rabbit antithymocyte globulin and OKT3 provide similar protection against early rejection with a relatively low risk of early infection. (3) T-cell markers do not predict early rejection after OKT3. PMID- 2108283 TI - Hemodynamic response to pumpless extracorporeal membrane oxygenation. AB - Respiratory support by means of arteriovenous extracorporeal membrane oxygenation driven by systemic arterial pressure, in contrast to pump-driven venoarterial extracorporeal membrane oxygenation, is attractive because of its simplicity and lack of trauma to formed blood elements. Although arteriovenous extracorporeal membrane oxygenation has been shown to improve arterial blood gases, useful levels of arteriovenous extracorporeal membrane oxygenation shunt flow may exert detrimental effects on systemic and pulmonary hemodynamics. Therefore the hemodynamic consequences of arteriovenous extracorporeal membrane oxygenation were studied in 11 dogs that were anesthetized, heparinized, and their lungs mechanically ventilated (FIO2 = 0.21) before and after induction of oleic acid pulmonary edema. The data indicate that arteriovenous extracorporeal membrane oxygenation shunt flows adequate to improve arterial blood gases resulted in significant changes in peripheral vascular resistance (-46%; p less than 0.05), systemic arterial blood pressure (-20%; p less than 0.05), and cardiac output (+110%; p less than 0.05). Dopamine infusion (5 micrograms/kg/min) proved to be more effective than volume expansion (15 ml/kg) in maintaining cardiac output, arterial blood pressure, and arterial blood gases. We conclude that pumpless arteriovenous extracorporeal membrane oxygenation, at flow rates adequate for respiratory support, can adversely alter systemic hemodynamics. However, these effects can be beneficially modulated by a moderate dose of inotropic medication. PMID- 2108284 TI - A classification system for long-staying psychiatric patients. AB - Data on a sample of 890 Veteran's Administration long-staying psychiatric patients were studied to develop a classification system that explains actual daily resource use. Disturbed patients with lengths of stay of less than three years and those with psychotic conditions who are not withdrawn represent the two groups found to use significantly more resources in their daily care. The Long Stay Psychiatric Patient Classification (LPPC) System, with six categories, explains 11.4% of the variability in per diem resource use and can be used for case-mix adjustment of payments for psychiatric care. PMID- 2108285 TI - Risk reduction from low osmolality contrast media. What do patients think it is worth? AB - Decisions regarding the use of and reimbursement for new medical technologies frequently involve complex cost-quality trade-offs. Among physicians, hospital administrators, and insurers, interindividual variation in the value of benefits attributable to these technologies often leads to conflicting opinions about their appropriate use. Although society now encourages patient involvement in such decisions, few methods for obtaining patient valuations have been developed and systematically applied. In order to assess patient valuations of a particular new technology, low osmolality contrast media (LOM), a survey of 100 outpatients was conducted. Participants were asked about their willingness to pay (WTP) for the benefits of this expensive medical technology. Of the 95 subjects who completed the study questionnaire, a majority were unwilling to pay the minimum extra per procedure cost of LOM ($50) in return for a reduced risk of minor side effects alone (pain, nausea, hives, and flushing). For a reduced risk of both major side effects (death, renal insufficiency, severe allergic reaction, and cardiac arrhythmia) and minor side effects, the median WTP was $50; patient income and education were directly associated with WTP $50 or more. We conclude that similar WTP surveys may be helpful in addressing other difficult cost quality issues. PMID- 2108286 TI - Spend-down of assets before Medicaid eligibility among elderly nursing-home recipients in Michigan. AB - Many elderly persons enter nursing homes as private pay clients, spend their available life savings, and then apply for medical assistance under Medicaid after their assets are depleted. However, reliable data on the size and characteristics of this "spend-down" population have been lacking. This study used Medicaid claims and enrollment data to identify the proportion of elderly Medicaid nursing-home users who originally entered nursing homes as private pay clients versus those eligible for Medicaid before or concurrent with, their nursing-home admission. The study population consisted of all elderly nursing home users receiving Medicaid in Michigan in 1984, a total of 36,898 unduplicated recipients. Findings indicated that "spend-downers" comprised 27.2% of all elderly users. Once on Medicaid, spend downers exhibited similar nursing-home utilization patterns as other groups, but incurred lower Medicaid claims because they contributed more to the cost of their nursing-home care. In aggregate, the State of Michigan Medicaid program spent $75.4 million on nursing-home services in 1984 for elderly persons who spent down to eligibility in a nursing home. These data are relevant to state policy initiatives to reduce Medicaid spending for nursing-home care by encouraging potential spend downers to purchase long term care insurance. PMID- 2108287 TI - Factors associated with length of stay in hospice. PMID- 2108288 TI - [Experiences from the Birmingham Children's Hospital. One year and 10,000 hospital days of nutritional support]. PMID- 2108289 TI - Reliable insertion of nasogastric and enteral feeding tubes. PMID- 2108290 TI - Chronopharmacological study of furosemide; (V). Influence of pretreatment with 6 hydroxydopamine. AB - Our previous indirect evidences suggested that the adrenergic nervous system is involved in the mechanisms responsible for the time-dependent changes in the effects of furosemide in Wistar rats. In the present study, the role of this system was examined more directly by means of 6-hydroxydopamine-induced sympathectomy. Thirty mg/kg of 6-hydroxydopamine hydrobromide (6-OH-DA) (n = 9) or its vehicle alone (n = 9) was injected intra-arterially (i.a.) twice in Wistar rats. Furosemide (5 mg/kg) was administered i.a. at 1000 hrs (03HALO*) or at 2200 hrs (15HALO). Urine was collected for 60 min after the drug and urinary excretion of sodium and furosemide were determined respectively. Urine volume and urinary excretion of sodium and furosemide were significantly greater at 1000 hrs (03HALO) than at 2200 hrs (15HALO) in the vehicle-injected rats as observed in the previous study. However these administration-time-dependent changes in the effects of furosemide disappeared in the rats with 6-OH-DA. Thus, the present study provides more direct evidence and supports our original hypothesis concerning the mechanisms of this chronopharmacological phenomenon of the agent. Since 6-OH-DA does not penetrate the central nervous system from the blood stream, the present data also indicate that the peripheral adrenergic system is involved in this event. PMID- 2108291 TI - A meta-analysis of the effects of nursing interventions on children and parents. PMID- 2108292 TI - The National Vaccine Injury Compensation Program. PMID- 2108293 TI - Legal alternatives for fetal injury. PMID- 2108294 TI - Cause of concern. PMID- 2108295 TI - Preterm-birth prevention--FYI. PMID- 2108297 TI - A question of ethics. PMID- 2108296 TI - Too busy for research? Collaboration: an answer. PMID- 2108298 TI - Weaning infants from sedation. PMID- 2108299 TI - Culturally sensitive support for grieving parents. PMID- 2108300 TI - Rational management of a child's acute fever. PMID- 2108301 TI - A risk of blood transfusions for premature infants. PMID- 2108302 TI - Postpartum depression as a family problem. PMID- 2108303 TI - In utero lead exposure. PMID- 2108304 TI - Assessment of coping mechanisms used by parents and children with chronic illness. PMID- 2108305 TI - Inference of haplotypes from PCR-amplified samples of diploid populations. AB - Direct sequencing of genomic DNA from diploid individuals leads to ambiguities on sequencing gels whenever there is more than one mismatching site in the sequences of the two orthologous copies of a gene. While these ambiguities cannot be resolved from a single sample without resorting to other experimental methods (such as cloning in the traditional way), population samples may be useful for inferring haplotypes. For each individual in the sample that is homozygous for the amplified sequence, there are no ambiguities in the identification of the allele's sequence. The sequences of other alleles can be inferred by taking the remaining sequence after "subtracting off" the sequencing ladder of each known site. Details of the algorithm for extracting allelic sequences from such data are presented here, along with some population-genetic considerations that influence the likelihood for success of the method. The algorithm also applies to the problem of inferring haplotype frequencies of closely linked restriction-site polymorphisms. PMID- 2108306 TI - Evolution of the glucose dehydrogenase gene in Drosophila. AB - The glucose dehydrogenase genes (Gld) of Drosophila melanogaster, of D. pseudoobscura, and of D. virilis have been isolated and compared with each other in order to identify conserved and divergent aspects of their structure and expression. The exon/intron structure of Gld is conserved. The Gld mRNAs are similar, with a range of 2.6-2.8 kb among the three species. All three species exhibit peaks of Gld expression during every major developmental stage, although considerable variation in the precise timing of these peaks exists between species. Interspecific gene transfer experiments demonstrate that the regulation and function of the D. pseudoobscura Gld is similar enough to the homologous gene in D. melanogaster to substitute for its essential role in the eclosion process. Comparison of the putative promoter sequences has identified both shared and divergent sequence elements which are likely responsible, respectively, for the conserved and divergent patterns of expression observed. The entire coding sequences of the pseudoobscura and melanogaster Gld genes are presented and shown to encode a 612-amino-acid pre-protein. The inferred amino acid sequences are 92% conserved between the two species. In general the intronic regions of Gld are unusually well conserved. PMID- 2108307 TI - [Isoenzymatic pattern of Trypanosoma cruzi Y strain after specific chemotherapy]. AB - The isoenzyme pattern of the Trypanosoma cruzi Y strain recovered from mice inoculated with 15 x 10(4) blood trypomastigotes and previously treated with either Bay 2502 (Nifurtimox) or Ro 7-1051 (Benzonidazol) was analyzed in the following situations: a) strain resistant to Bay 2502 and again treated with the same drug; b) strain resistant to Bay 2502 and treated with Ro 7-1051; c) strain resistant to Ro 7-1051 and treated with that same drug. Although marked drug resistance was noted in all cases, the isoenzyme pattern of the Y strain for GPI, PGM, ALAT and ASAT remained throughout the same. The pattern was similar to that of the Peruvian strain, which also belongs to the same strain Type of the Y strain, but differed from those of the 21 SF (Type II) and Colombian (Type III) strains. Thus, the appearance of drug resistance in T. cruzi strain was not associated with a change in its isoenzymatic pattern. PMID- 2108308 TI - [Natural infection of the anal glands of the opossum (Didelphis albiventris) by Trypanosoma cruzi in the municipality of Bambui--MG, Brazil]. AB - Out of 87 opossums, Didelphis albiventris, captured in the Bambui area (Minas Gerais State), 32 (36.7%) were found infected by Trypanosoma cruzi; the rates varied according to whether the specimens originated from sylvan, rural peridomiciliar or urban surroundings, being 34.9, 81.8 and 7.7 respectively. From 20 of the infected opossums the anal glands were repeatedly examined and found positive in only one (5%) specimen (GA 9), with 7 positive examinations out of 17 performed through an 18-months periods. Material from these glands produced patent parasitemia in opossums and sub-patent infections in mice. Isolates from the opossum GA 9, obtained through xenodiagnoses and hemocultures and from cultures of the infected anal glands fitted into zymodeme Z1. PMID- 2108309 TI - Pharmacokinetic aspects of tert-butylaminoethyl disulfide, an experimental drug against schistosomiasis in mice. AB - A preliminary study of the pharmacokinetic parameters of t-Butylaminoethyl disulfide was performed after administration of two different single doses (35 and 300 mg/kg) of either the cold or labelled drug. Plasma or blood samples were treated with dithiothreitol, perchloric acid, and, after filtration, submitted to further purification with anionic resin. In the final step, the drug was retained on a cationic resin column, eluted with NaCl 1M and detected according to the method of Ellman (1958). Alternatively, radioactive drug was detected by liquid scintillation counting. The results corresponding to the smaller dose of total drug suggested a pharmacokinetic behavior related to a one open compartment model with the following parameters: area under the intravenous curve (AUCi.v.): 671 +/ 14; AUCoral: 150 +/- 40 micrograms.min.ml-1; elimination rate constant: 0.071 min-1; biological half life: 9.8 min; distribution volume: 0.74 ml/g. For the higher dose, the results seemed to obey a more complex undetermined model. Combining the results, the occurrence of a dose-dependent pharmacokinetic behavior is suggested, the drug being rapidly absorbed and rapidly eliminated; the elimination process being related mainly to metabolization. The drug seems to be more toxic when administered I.V. because by this route it escapes first pass metabolism, while being quickly distributed to tissues. The maximum tolerated blood level seems to be around 16 micrograms/ml. PMID- 2108311 TI - The nursing shortage and long-term care: the solution. PMID- 2108310 TI - [Treatment of hypogonadism and infertility in the male. I]. PMID- 2108312 TI - Foodborne hepatitis A--Alaska, Florida, North Carolina, Washington. PMID- 2108313 TI - Supplementary statement: change in administration schedule for haemophilus b conjugate vaccines. PMID- 2108314 TI - Compendium of animal rabies control, 1990. National Association of State Public Health Veterinarians, Inc. PMID- 2108315 TI - Site-directed mutagenesis of the SH2- and SH3-coding domains of c-src produces varied phenotypes, including oncogenic activation of p60c-src. AB - The products of the viral and cellular src genes, p60v-src and p60c-src, appear to be composed of multiple functional domains. Highly conserved regions called src homology 2 and 3 (SH2 and SH3), comprising amino acid residues 88 to 250, are believed to modulate the protein-tyrosine kinase activity present in the carboxy terminal halves of the src proteins. To explore the functions of these regions more fully, we have made 34 site-directed mutations in a transformation-competent c-src gene encoding phenylalanine in place of tyrosine 527 (Y527F c-src). Twenty of the new mutations change only one or two amino acids, and the remainder delete small or large portions of the SH2-SH3 region. These mutant alleles have been incorporated into a replication-competent Rous sarcoma virus vector to examine the biochemical and biological properties of the mutant proteins after infection of chicken embryo fibroblasts. Four classes of mutant proteins were observed: class 1, mutants with only slight differences from the parental gene products; class 2, mutant proteins with diminished transforming and specific kinase activities; class 3, mutant proteins with normal or enhanced specific kinase activity but impaired biological activity, often as a consequence of instability; and class 4, mutant proteins with augmented biological and catalytic activities. In general, there was a strong correlation between total kinase activity (or amounts of intracellular phosphotyrosine-containing proteins) and transforming activity. Deletion mutations and some point mutations affecting residues 109 to 156 inhibited kinase and transforming functions, whereas deletions affecting residues 187 to 226 generally had positive effects on one or both of those functions, confirming that SH2-SH3 has complex regulatory properties. Five mutations that augmented the transforming and kinase activities of Y527F c-src [F172P, R175L, delta(198-205), delta(206-226), and delta(176-226)] conferred transformation competence on an otherwise normal c-src gene, indicating that mutations in SH2 (like previously described lesions in SH3, the kinase domain, and a carboxy-terminal inhibitory domain) can activate c-src. PMID- 2108316 TI - A large protein containing zinc finger domains binds to related sequence elements in the enhancers of the class I major histocompatibility complex and kappa immunoglobulin genes. AB - A cDNA from a B-cell library was previously isolated that encodes a sequence specific DNA-binding protein with affinities for related sites in a class I major histocompatibility complex (MHC) and kappa immunoglobulin gene enhancers. We report here approximately 6.5 kilobases of sequence of the MBP-1 (MHC enhancer binding protein 1) cDNA. MBP-1 protein has a molecular weight predicted to be greater than 200,000. A DNA-binding domain with high affinity for the MHC enhancer sequence TGGGGATTCCCCA was localized to an 118-amino-acid protein fragment containing two zinc fingers of the class Cys2-X12-His2. Analysis of expression of MBP-1 mRNA revealed relatively high expression in HeLa cells and in a human retinal cell line, with lower levels in Jurkat T cells and in two B-cell lines. Interestingly, expression of MBP-1 mRNA was inducible by mitogen and phorbol ester treatment of Jurkat T cells and by serum treatment of confluent serum-deprived human fibroblasts. PMID- 2108317 TI - Structure and transcription of the Drosophila melanogaster vermilion gene and several mutant alleles. AB - The nucleotide sequence and intron-exon structure of the Drosophila melanogaster vermilion (v) gene have been determined. In addition, the sites of several mutations and the effects of these mutations on transcription have been examined. The major v mRNA is generated upon splicing six exons of lengths (5' to 3') 83, 161, 134, 607, 94, and 227 nucleotides (nt). A minor species of v mRNA is initiated at an upstream site and has a 5' exon of at least 152 nt which overlaps the region included in the 83-nt exon of the major v RNA. The three v mutations, v1, v2, and vk, which can be suppressed by mutations at suppressor of sable, su(s), are insertions of transposon 412 at the same position in exon 1, 36 nt downstream of the major transcription initiation site. Despite the 7.5-kilobase insertion in these v alleles, a reduced level of wild-type-sized mRNA accumulates in suppressed mutant strains. The structure and transcription of several unsuppressible v alleles have also been examined. The v36f mutation is a B104/roo insertion in intron 4 near the splice donor site. A mutant carrying this alteration accumulates a very low level of mRNA that is apparently polyadenylated at a site within the B104/roo transposon. The v48a mutation, which deletes approximately 200 nt of DNA, fuses portions of exons 3 and 4 without disruption of the translational reading frame. A smaller transcript accumulates at a wild type level, and thus an altered, nonfunctional polypeptide is likely to be synthesized in strains carrying this mutation. The v(H2a) mutants has a P element insertion in exon 6 within the coding region. PMID- 2108318 TI - Autoinduction of transforming growth factor beta 1 is mediated by the AP-1 complex. AB - The multifunctional actions of transforming growth factor beta 1 (TGF-beta 1) indicate that it has a pivotal control function in many physiological and pathological processes. An important property of TGF-beta 1 is its ability to activate its own mRNA expression and thereby increase its own secretion. Two distinct regions of the promoter of the TGF-beta 1 gene are responsive to autoregulation: one 5' to the upstream transcriptional start site and another located between the two major start sites. In both promoter regions, autoinduction is mediated by binding of the AP-1 (Jun-Fos) complex. An important contribution to this positive regulation is the autoactivation of c-jun transcription by AP-1. Cotransfection of antisense c-jun or antisense c-fos expression vectors prevents TGF-beta 1 autoinduction. These results demonstrate that both components of the AP-1 complex are required for TGF-beta 1 autoinduction. Induction of jun expression by TGF-beta 1, as well as jun autoinduction, may amplify the action of TGF-beta 1 during normal development and oncogenesis. PMID- 2108320 TI - Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. AB - A mixed-oligonucleotide probe was used to identify four ras-like coding sequences in a human teratocarcinoma cDNA library. Two of these sequences resembled the rho genes, one was closely related to H-, K-, and N-ras, and one shared only the four sequence domains that define the ras gene superfamily. Homologs of the four genes were found in genomic DNA from a variety of mammals and from chicken. The genes were transcriptionally active in a range of human cell types. PMID- 2108319 TI - Oncogene N-ras mediates selective inhibition of c-fos induction by nerve growth factor and basic fibroblast growth factor in a PC12 cell line. AB - A cell line was generated from U7 cells (a subline of PC12 rat pheochromocytoma cells) that contains a stably integrated transforming mouse N-ras (Lys-61) gene under the control of the long terminal repeat from mouse mammary tumor virus. Such cells, designated UR61, undergo neuronal differentiation upon exposure to nanomolar concentrations of dexamethasone, as a consequence of expression of the activated N-ras gene (I. Guerrero, A. Pellicer, and D.E. Burstein, Biochem, Biophys. Res. Commun. 150:1185-1192, 1988). Exposure of UR61 cells to either nerve growth factor (NGF) or basic fibroblast growth factor (bFGF) results in a marked induction of c-fos RNA, with kinetics paralleling those of NGF- or bFGF induced expression of c-fos RNA in PC12 cells. Dexamethasone-induced expression of activated N-ras p21 results in blocking of c-fos RNA induction by NGF or bFGF in a time-dependent manner. Activated N-ras p21-mediated inhibition of c-fos RNA induction in UR61 cells is selective for NGF and bFGF and is not due to selective degradation of c-fos RNA. Normal and transforming N-ras can trans activate the chloramphenicol acetyltransferase gene linked to mouse c-fos regulatory sequences when transient expression assays are performed. Our observations suggest that N ras p21 selectively interacts with pathways involved in induction of c-fos expression which initiate at the receptors for NGF and bFGF. PMID- 2108321 TI - brlA requires both zinc fingers to induce development. AB - Expression of the Aspergillus nidulans brlA gene induces a developmental pathway leading to the production of asexual spores. We have introduced mutations into brlA that are expected to disrupt either or both Cys2-His2 Zn(II) coordination sites postulated to exist in the BrlA polypeptide. The resultant brlA alleles fail to induce either the asexual reproductive pathway or the expression of development-specific genes. These data support the hypothesis that brlA encodes a nucleic acid-binding protein whose activity requires each of two zinc fingers. PMID- 2108322 TI - Three-dimensional structure of a hybrid light chain dimer: protein engineering of a binding cavity. AB - An attempt was made to engineer a binding site and check its structure by X-ray analysis. Two human light chains (Mcg and Weir), with "variable" domain sequences differing in 36 positions, were hybridized into a heterologous dimer and crystallized in ammonium sulfate by the same procedure used for the trigonal form of the Mcg dimer. The three-dimensional structure of the hybrid was determined at 3.5-A resolution by difference Fourier analysis, interactive model building with computer graphics and crystallographic refinement. In the heterologous dimer, the Weir protein behaved as the structural analog of the heavy chain in an antigen binding fragment, while the Mcg protein assumed the role of the light chain component. The hybrid and the Mcg dimer were closely similar in overall structure, an observation probably correlated with the deliberate cleavage of the intrachain disulfide bond in the variable domain of the Weir protein during the hybridization procedure. Examination of the crystal structure of the hybrid suggested that the cleavage resulted in the relaxation of restraints which might otherwise have interfered with the formation of an Mcg-like dimer. There were six substitutions among the residues lining the binding cavities of the hybrid and Mcg dimer. These substitutions significantly affected the sizes, shapes and binding properties of the two cavities. PMID- 2108323 TI - Analysis of the expression of murine lambda genes transfected into immunocompetent cell lines. AB - Hybridoma cell lines were transfected with plasmids containing either a rearranged lambda 1 or a rearranged lambda 2 mouse gene. The levels of lambda chains synthesized by these transfectants were very low or undetectable. Activation of the expression of the lambda 2 gene was achieved artificially by deleting a portion of the region upstream of the promoter. Analogous deletions in the fragment containing the lambda 1 gene did not result in gene activation suggesting that the upstream sequences of lambda 1 and lambda 2 genes have diverged enough to allow differential regulation of their expression. However, both genes were activated by insertion, at a position upstream of the promoter, of a fragment containing the K-chain gene enhancer. These results suggest that the complete set of sequence elements that mediate lambda gene activation during normal B-cell differentiation are not all contained in the fragments of genomic DNA cloned so far, and thus, at least some of them must be located at a considerable distance from the promoter. PMID- 2108324 TI - The regulation of exogenous and endogenous class I MHC genes in a human tumor cell line, K562. AB - Previous studies have implied the existence of a trans-dominant intracellular repressor able to down-regulate the expression of the entire family of class I MHC genes in the genome of the K562 erythroleukemia cell line. This study demonstrates, however, that the transfection of human or murine class I genes into K562 cells leads to the cell surface expression of the transfected MHC gene product in all situations, even when several kilobases of 5' flanking sequence were included in the transfected genes. The endogenous cellular class I MHC genes remained repressed in the transfected cells. These findings suggest that repression of class I MHC gene expression in K562 may not be mediated predominantly by a trans-dominant repressor of MHC gene expression; rather, other more complex regulatory influences might exist. PMID- 2108325 TI - [Vitamin K deficiency with erythromycin. Observation of a boy treated with valproate]. AB - A nine year old boy had been treated with valproic acid during one and a half years because of a grand mal epilepsy. Under an additional medication with erythromycin succinate syrup this patient developed a deficiency of prothrombin complex, which was reversible immediately after oral intake of vitamin K. In this case it is assumed that the simultaneous application of both valproic acid and erythromycin succinate seems to suppress the vitamin K producing intestinal tract bacteria, which has not been reported in the literature so far. PMID- 2108326 TI - Diabetic ketoacidosis: in search of zero mortality. PMID- 2108327 TI - The ring-infected erythrocyte surface antigen protein of Plasmodium falciparum is phosphorylated upon association with the host cell membrane. AB - The ring-infected erythrocyte surface antigen (RESA) is a 155-kDa malarial polypeptide which is released from merozoites and becomes associated with the erythrocyte membrane at the time of invasion. Inside-out vesicles (IOVs) prepared from Plasmodium falciparum-infected erythrocytes contain RESA, presumably bound to the membrane skeleton, as it is largely insoluble in Triton X-100. When these IOVs were incubated with [gamma-32P]ATP, a 155-kDa polypeptide was labeled in IOVs from infected, but not from uninfected erythrocytes. Immunoprecipitation using specific rabbit antisera confirmed that RESA is indeed a phosphoprotein. Phosphoamino acid analysis revealed phosphoserine and a small amount of phosphothreonine, but no phosphotyrosine. Labeling of intact parasitized erythrocytes with inorganic [32P]phosphate for several hours in culture resulted in RESA in Triton-insoluble extracts being phosphorylated. Labeling of synchronized parasites showed that RESA was phosphorylated only when it became associated with the erythrocyte membrane, and although RESA was abundant in mature parasites, it was not phosphorylated. RESA, released into the culture supernatants during the growth of P. falciparum, bound to IOVs prepared from normal uninfected erythrocytes, and subsequent labeling with [gamma-32P]ATP resulted in the phosphorylation of RESA. The evidence suggests that RESA is phosphorylated by an erythrocyte membrane kinase and probably not by a parasite encoded enzyme. PMID- 2108328 TI - Characterisation of an alkaline peptidase of Trypanosoma cruzi and other trypanosomatids. AB - A peptidase activity was purified from extracts of Trypanosoma cruzi on the basis of its ability to cleave benzoyl-arginine-p-nitroanilide. The enzyme was considered to be a cysteine-type peptidase with unusually low sensitivity to E 64. It has a pH optimum of about 8.0 for p-nitroanilides, and cleaves peptide bonds on the carboxyl side of arginine and, to a lesser extent, lysine residues. Cleavage of different substrates occurred at rates that were determined by their catalytic constants (kcat): the peptidase had the same Michaelis constant (about 30 microM) for all substrates tested. Evidence is presented that the peptidase is the major cysteine peptidase in T. cruzi extracts that cleaves p-nitroanilides next to basic amino acid residues at pH 8. The enzyme was detected in all stages of the life cycle of T. cruzi. Furthermore, evidence is presented, based on pH optima, inhibitor sensitivity, substrate specificity and kinetics, and electrophoretic mobility, that a similar or identical enzyme occurs in fifteen other species of trypanosomatid. PMID- 2108329 TI - Continuous synthesis of glycogen by individual worm pairs of Schistosoma mansoni inside the veins of the final host. AB - Hamsters infected with Schistosoma mansoni were operated upon to install a permanent canula into their blood stream. After recovery of the hamster, this canula was used for the injection of radioactively labelled glucose. In this way the glycogen metabolism of S. mansoni could be studied while the parasites remained undisturbed in their natural habitat. The consecutive injection of [U 14C]glucose and [1-3H]glucose permitted an analysis of possible changes in the glycogen synthesis of individual worm pairs with time. The results showed that the synthesis of glycogen by each worm pair was fairly constant with time. Furthermore, all individual worm pairs synthesised glycogen continuously; not even 2 min passed without its formation. Only small differences in glycogen synthesis were observed between parasites isolated from different locations in the veins of the hamster. These results exclude the possibility that the worm pairs had alternating periods of glycogen synthesis and degradation, and they also disprove the idea that synthesis and degradation occur at two different sites in the bloodstream of the hamster. The experiments further showed that glycogen synthesis was proportional to the amount of glycogen already present, which in turn was shown to be proportional to the size of the parasite. From this study it can be concluded that the replenishment of the endogenous glycogen reserves of S. mansoni is not induced by a marked decrease in the glycogen levels, but occurs slowly and continuously. PMID- 2108330 TI - Effects of oxygen concentration on the intermediary metabolism of Leishmania major promastigotes. AB - Leishmania major promastigotes grown in late log phase were incubated with glucose as sole exogenous carbon source in the presence of 5% CO2 and the amounts of glucose consumed and of the major products formed--succinate, pyruvate, alanine, acetate, glycerol, and D-lactate--were measured as a function of pO2. Glucose consumption increased as pO2 was lowered to 6% (a positive Pasteur effect) and then declined to the same level at 95% N2 as at 95% O2. The production of D-lactate and of glycerol increased as pO2 dropped from 95%, reaching a maximum at about 2% O2. Succinate production, however, increased dramatically when pO2 was reduced to 6% and remained at that level with further reduction of pO2. The amount of succinate produced relative to the amount of glucose carbon consumed suggests utilization of an endogenous carbon source. Acetate production did not change between 95% O2 and 6% O2 and then declined with decreasing pO2. These observations suggest the presence of two sensors, one with a high and one with a low affinity for oxygen. When glycerol or alanine were the only exogenous sources of carbon, the primary products released were acetate and succinate. Acetate production from alanine declined slightly as pO2 was reduced to 2%, and then dropped markedly when pO2 was reduced to 0%. Acetate production from glycerol increased over 4-fold when the pO2 was reduced from 95% to 4%, and then declined with further reduction in pO2. No succinate was formed from either substrate until complete anaerobiosis. This pattern of response, while differing from that when glucose was sole exogenous carbon source, is also consistent with the regulation of metabolism by a high and a low affinity O2 sensor. Cells from cultures in early stationary phase, before the appearance of metacyclic forms, consumed glucose at about the same rate as log phase promastigotes, but did not show a Pasteur effect. Stationary cells also consumed glycerol at the same rate as did log phase promastigotes, but consumed alanine at a much lower rate. Reduction of pO2 affected product formation from each of these substrates differently than for log phase promastigotes, demonstrating the sensitivity of several pathways of intermediary metabolism to regulation by pO2 during the transition from log to stationary phase. PMID- 2108331 TI - Do the poor cost more? A multihospital study of patients' socioeconomic status and use of hospital resources. AB - There is controversy about whether hospitalized poor patients use more resources and whether hospitals that provide care for the poor therefore merit supplementary payment under per-case prospective payment systems. We previously reported that patients of low socioeconomic status with connective-tissue disease had longer hospital stays and higher costs than patients of higher socioeconomic status at a single hospital. To examine the generalizability of this phenomenon, we interviewed 16,908 (83 percent) of 20,278 consecutive adult patients (excluding obstetrical and psychiatric patients) admitted in 1987 to five Massachusetts hospitals, to obtain information on three direct measures of socioeconomic status (income, occupation, and education). We divided each measure into three strata. Thus, there were 15 comparisons--three measures of socioeconomic status applied to each of five hospitals. After excluding outliers and adjusting for diagnosis-related group (DRG), we found that the patients of the lowest socioeconomic status had hospital stays 3 to 30 percent longer than those of patients of higher status, the differences varying with the hospital and the indicator of socioeconomic status (P less than or equal to 0.05 for 11 of the 15 comparisons). Hospital charges were 1 to 18 percent higher for the patients of lowest socioeconomic status than for those of higher status (P less than or equal to 0.05 for 9 of 15 comparisons). When we adjusted for age, severity of illness, and DRG, the patients of lowest socioeconomic status had longer stays than those of higher status in 14 of 15 comparisons (P less than 0.05 for 7 of the 15) and higher charges in 13 of 15 comparisons (P less than 0.05 for 6 of the 15). The differences between patients of high and low status ranged up to 21 percent for length of stay and 13 percent for charges. Our findings suggest that hospitalized patients of lower socioeconomic status have longer stays and probably require more resources. Supplementary payments to hospitals for the treatment of poor patients merit further consideration. PMID- 2108332 TI - New B-M group 'AIDS' drug for 'investigational use'. PMID- 2108333 TI - Sex, growth and chance. PMID- 2108334 TI - [Norplant]. PMID- 2108335 TI - [Norplant in The Netherlands]. PMID- 2108336 TI - Ten years of turbulence. PMID- 2108337 TI - Education and experience. Part 2. PMID- 2108338 TI - Wide open management. PMID- 2108339 TI - Learn management skills, the outward bound way. PMID- 2108340 TI - Elderly care: cinderella goes to the ball at last. PMID- 2108341 TI - Education in the German Democratic Republic. PMID- 2108342 TI - School nursing: Southampton's health appraisal pilot study. PMID- 2108343 TI - Leg ulcers: the quiet epidemic below the knee. PMID- 2108344 TI - Clinical budgeting--a positive development? PMID- 2108345 TI - Ten is the countdown to twenty-one! PMID- 2108346 TI - Selling out. PMID- 2108348 TI - Contracts of employment. PMID- 2108347 TI - Coming and going. PMID- 2108349 TI - Afghanistan: battling for peace. PMID- 2108351 TI - Gastroenterology: gastrointestinal endoscopy--clinical practice. PMID- 2108350 TI - Setting standards of compassion. PMID- 2108353 TI - Psychodynamic models in relationships. PMID- 2108352 TI - Accountability in nursing practice. PMID- 2108354 TI - Health visiting: health and homelessness. PMID- 2108355 TI - Learning to care for the spirit. PMID- 2108356 TI - The support worker--the way forward for the 1990s. PMID- 2108358 TI - Caring for the consumer. PMID- 2108357 TI - For practice and patient. PMID- 2108359 TI - Managing the risk. PMID- 2108360 TI - Focus on mental handicap nursing. PMID- 2108361 TI - Mental handicap nursing. Project 2000: policy and possibilities. PMID- 2108362 TI - Mental handicap nursing. Learning from history. PMID- 2108364 TI - Health visiting and school nursing. PMID- 2108363 TI - Mental handicap nursing. Defeating phobias in the community. PMID- 2108365 TI - Counselling services for adolescents. PMID- 2108366 TI - The Cassel: casualties of closure. PMID- 2108367 TI - Nursing patients with a continent urinary diversion. PMID- 2108368 TI - Children of 'The Troubles'. PMID- 2108369 TI - Psychodynamic experience in the community. PMID- 2108371 TI - Patients' needs or professionalization? PMID- 2108370 TI - Setting the scene for the revolution. PMID- 2108372 TI - Issues in health service planning. PMID- 2108373 TI - Nurse practitioners--everybody's relative but nobody's baby. PMID- 2108374 TI - Paying for performance. PMID- 2108376 TI - Thoughts about theories. PMID- 2108375 TI - Fears for the future. PMID- 2108377 TI - Independent sector. Nurse-training initiatives. PMID- 2108378 TI - Independent sector. Range and experience. PMID- 2108379 TI - South Africa: opening race. PMID- 2108381 TI - Nurses' pay: unkind cuts. PMID- 2108380 TI - Improving the care of bereaved parents. PMID- 2108382 TI - Current trends in stoma care. PMID- 2108383 TI - Why nurses leave their jobs. PMID- 2108384 TI - Learning to cope with mental illness. PMID- 2108386 TI - Poverty and health. PMID- 2108385 TI - The potential of professional practice. PMID- 2108387 TI - Calculated and informed risks. PMID- 2108388 TI - Paper chase. PMID- 2108389 TI - A Royal Commission for the year 2000? PMID- 2108390 TI - Paediatric nursing. PMID- 2108391 TI - Paediatric nursing. Change in the 1990s. PMID- 2108392 TI - Paediatric nursing. Home care for children. PMID- 2108393 TI - Paediatric nursing. Oncology in the 1990s. PMID- 2108394 TI - Index of light kappa/lambda and lambda/kappa chains in monoclonal gammopathies. AB - Concentrations of the light chains kappa and lambda were determined by simple radial immunodiffusion in the blood sera of 437 patients with monoclonal gammopathies. The kappa/lambda index was calculated in monoclonal gammopathies with the antigenic type of kappa light chains, while in monoclonal gammopathies with the antigenic type of lambda light chains the lambda/kappa index was calculated. The results obtained in malignant monoclonal gammopathies were compared with the results obtained in monoclonal gammopathies of undetermined significance for IgG and IgM paraproteinemias. Differences of high statistical significance were established (for IgG and IgA p less than 0.001, for IgM p less than 0.005) and thus the light-chain index can be used as another marker in differential diagnosis of monoclonal gammopathies. PMID- 2108395 TI - [Slowing the progression of Parkinson syndrome by early administration of deprenyl]. PMID- 2108396 TI - Injection of tissue plasminogen activator to prevent delayed vasospasm. PMID- 2108397 TI - [The epidemiology of non-A, non-B hepatitis (NANB). A review of the literature]. AB - Non-A, non-B hepatitis (NANB) is, after type B hepatitis, the most frequently encountered form of hepatitis. Parenteral transmission and apparently nonparenteral or "sporadic" forms are described. The epidemiology of this new form of hepatitis is examined in the light of personal experience and of reported data. PMID- 2108398 TI - [Clinico-epidemiologic considerations in cases of acute viral non-A, non-B hepatitis (NANB)]. AB - Personal experience with a series of 69 cases of non-A, non-B viral hepatitis out of 164 cases of acute viral hepatitis observed at hospital admission between January 1985 and June 1988 is reported. Agreement is expressed with other Italian series as regards the incidence of sex, of the most involved age classes, of the most affected professional categories and of the incubation period of posttransfusional forms. The prevalence of sporadic forms over those transmitted intraparenterally and more prolonged course in icterus patients and in parenteral forms is pointed out. PMID- 2108399 TI - [Follow-up of blood and urinary amino acid concentrations in diabetic ketoacidosis in children]. AB - Plasma and urinary concentrations of amino acids were investigated during diabetic ketoacidosis (DKA) and 12, 24, 72 hours after initiation of therapy. In DKA plasma concentration of glutamic acid, asparaginic acid, valine, leucine and isoleucine significantly increased while that of asparagine and glutamine decreased compared to levels in well controlled diabetic patients. Despite the elevated urinary excretion of branched chain amino acids, histidine, serine and threonine, urinary excretion and clearance of glutamic acid, glutamine, glycine and taurine were reduced. Among the different amino acids histidine excretion had the highest variability. Strong correlation was found between the urinary excretion of several amino acids and that of the beta-2-microglobulin characterizing tubular dysfunction. Changes in the excretion of different amino acids reflect the altered metabolic state and renal function due to diabetic ketoacidosis. PMID- 2108400 TI - [High lactose content of the Lundh test meal adversely affects the reliability of the ALTAB test]. AB - The exocrine pancreatic function was examined in 20 patient without any detectable gastrointestinal disorder. We used 1 g 4(N-acetyl-L-thyrosil) aminobenzoic acid (ALTAB) an Lundh's test meal containing 25 g lactose, and the test was repeated with 3 g lactase (Galantase). The urine was collected for 6 hours to check PABA excretion in urine. Lactose intolerance was diagnosed in 10 patients on the basis of an increase of H2 in the breath at least 15 ppm after Lundh's test meal and/or diarrhoea after test in two hours if this diarrhoea could be prevented by giving Galantase orally. We measured PABA excretion in patients with and without lactose intolerance after Lundh's test meal: 17.8% (SD = 6.7) and 47% (SD = 13) respectively (p less than 0.001), and after Lundh's test meal with Galantase: 34.3% (SD = 12.7) and 43.6% (SD = 10.9) respectively. The increase after Galantase in the group with lactose intolerance was significant (p less than 0.01). CONCLUSIONS: 1. Lactose content of Lundh's test meal causes a considerable lactose load in patients with lactose intolerance. 2. Oral lactase enzyme usually normalises the result of ALTAB test. 3. It is necessary to detect lactose intolerance before use of Lundh's test meal. PMID- 2108401 TI - Chromosomal localization of the three members of the jun proto-oncogene family in mouse and man. AB - The three members of the jun proto-oncogene family c-jun, jun b and jun D were mapped on the mouse chromosome by in situ hybridization. The c-jun locus is on chromosome 4 subregion C5----C7, whereas jun B and jun D are co-localized on chromosome 8 subregion C. RFLP analysis of interspecific hybrids confirmed the mapping of jun B and D and showed that they are situated about 7.3 +/- 3.5 cM apart. Thus despite their possible origin from a single ancestral gene they are not closely linked on the chromosome. Using the same probes, we showed that the human genome also contains sequences homologous to the mouse jun B and jun D. They are located on human chromosome 19 p13.2, a region that may be involved in chromosomal translocation in acute lymphocytic leukemia (ALL), acute nonlymphocytic leukemia (ANLL) and malignant melanoma (MEL). Finally, the present data identify a new segmental homology between mouse and human chromosomes. PMID- 2108402 TI - Both Jun and Fos contribute to transcription activation by the heterodimer. AB - Comparison of the amino acid sequence of the three members of the mouse jun proto oncogene family, c-jun, jun B and jun D, reveals several homologous segments. The most C-terminal of them including a leucine zipper motif and a cluster of basic amino acids was previously identified as the DNA binding domain. By deletion analysis, we show that three conserved domains in the N-terminal region are crucial for transactivation by Jun homodimers. Only one of these is predicted to form an acidic amphipathic alpha-helix. The addition of Fos and the formation of Jun-Fos heterodimers strongly increases the transactivation level. Jun mutants that are inactive alone gain partial or full activity in the presence of Fos. This increase strongly depends on the presence of the C-terminal domain of Fos. These results show that in Jun-Fos heterodimers both the N-terminal part of Jun and the C-terminal part of Fos contribute to transactivation with a more pronounced role for the latter. PMID- 2108403 TI - Stimulation of adrenal medullary cells in vivo and in vitro induces expression of c-fos proto-oncogene. AB - The nuclear proto-oncogene, c-fos, has been implicated in the coordinated regulation of gene expression during cell proliferation and differentiation. In this study, we have demonstrated the induction of the c-fos gene products in differentiated cells of the adrenal medulla by non-mitogenic signals. Activation of adrenal medullary cells in vivo by insulin-induced hypoglycemia, and in vitro by nicotine or angiotensin resulted in the rapid and transient elevation of c-fos mRNA levels. Induction of the c-fos mRNA by angiotensin and nicotine were accompanied by the appearance of the c-fos protein. The increase in c-fos protein occurred initially in the cytoplasm and, later, in the nucleus, and it was co localized with tyrosine hydroxylase. Nuclear expression of the c-fos protein was also induced by veratridine, forskolin and the calcium ionophore A231287. The role of calcium in the regulation of the c-fos gene by angiotensin with nifedipine and inhibition of the effects of angiotensin with nifedipine and sphingosine, a protein kinase C inhibitor. Activation of the c-fos gene may play a role in the coordinated induction of genes involved in the long-term adaptation of adrenal medullary cells to increased functional demands. PMID- 2108404 TI - Mitogenesis induced by pp60v-src is not accompanied by increased expression of immediate early response genes. AB - Rat-1 cells infected with a temperature sensitive mutant of RSV (ts LA 29 Rat-1) can be rendered quiescent by serum deprivation at restrictive temperature. Shift to permissive conditions activates the v-src protein tyrosine kinase within 10 minutes and either this stimulus, or serum addition at restrictive temperature, leads to progression of the cell from G0 to G1, S-phase and mitosis. The effects of serum and temperature shift are not synergistic, suggesting that they may operate by convergent mechanisms. However, the characteristic serum-stimulated transient increases in transcripts of three immediate early response genes, c fos, c-jun and c-myc are absent or much reduced when mitogenesis in ts LA 29 Rat 1 is induced by pp60v-src. Nonetheless, upon activating the pp60v-src protein kinase there is a marked and rapid increase in the ability of ts LA 29 Rat-1 nuclear extracts to retard the gel migration of oligonucleotides containing the AP-1 binding site, indicating that pp60v-src activity leads to an enhanced functioning of Fos and Jun related proteins that may, in turn, affect their transcriptional activation. Furthermore, these findings, and comparison with those of other laboratories, suggest that the mitogenic and transforming activities of pp60v-src have different effects on the transcription of immediate early response genes. PMID- 2108406 TI - Effect of Klebsiella ozaenae on ciliary activity in vitro: implications in the pathogenesis of atrophic rhinitis. AB - Klebsiella ozaenae is a gram-negative rod that has been isolated with relative frequency from patients with atrophic rhinitis. The relationship of this bacterium to the pathogenesis of atrophic rhinitis is not understood, and whether this bacterium is simply an opportunistic colonizer of the injured nose or the etiologic agent of the disease is unclear. This study was designed to investigate a potential role for bacterially produced cilioinhibition as a mechanism for the pathogenesis of atrophic rhinitis. PMID- 2108405 TI - The human Evi-1 gene is located on chromosome 3q24-q28 but is not rearranged in three cases of acute nonlymphocytic leukemias containing t(3;5)(q25;q34) translocations. AB - The murine Evi-1 gene encodes a protein that has multiple 28-amino acid repeats containing the consensus sequence found in the zinc finger domains of many transcriptional regulatory proteins. Activation of the expression of the Evi-1 gene is frequently found in murine myeloid leukemias and leukemia cell lines and is due to retroviral insertions in the 5' region of the gene in either the Evi-1 or the CB-1/FIM3 common sites of viral integrations. To examine the role of the Evi-1 gene in human leukemias we have cloned regions of the human locus corresponding to the coding region of the gene and regions corresponding to the Evi-1 and CB-1/FIM3 common sites of integrations. Using these probes we demonstrate that the human Evi-1 gene maps to chromosome 3q24-q28 in a region that is translocated in acute nonlymphocytic leukemias with a t(3;5)(q25;q34). By in situ hybridization with metaphase chromosomes from one patient with a 3;5 translocation, the Evi-1 gene was found to be translocated to the derivative 5 chromosome. However, no rearrangements were detected by Southern blot analysis with DNAs from three patients with a t(3;5) using probes from the Evi-1 or CB 1/FIM3 loci. No Evi-1 transcripts were detected with RNA from leukemic blasts of one patient with a t(3;5). PMID- 2108407 TI - The effect of air flow and medial adductory compression on vocal efficiency and glottal vibration. AB - This study used an in vivo canine model to investigate the effects of varying vocal fold resistance by electrically stimulating the recurrent laryngeal nerve while monitoring medial adductory compression of the vocal folds, glottal airflow, and vocal intensity. The effects of increasing airflow on glottal vibration were also examined stroboscopically and by measurement of open quotient. The results indicated that increasing intensity by medial adductory compression was more efficient than by increasing airflow. Increasing airflow produced a significantly greater open quotient and vocal fold vibratory excursion. PMID- 2108409 TI - Photodynamic therapy for treatment of head and neck cancer. AB - Since 1975, photodynamic therapy has reportedly been effective in a variety of head and neck malignancies that failed traditional (conventional) therapy, including surgery, cryotherapy, chemotherapy, hyperthermia, and radiation therapy. Photodynamic therapy consists of the intravenous administration of (di)hematoporphyrin ether, a chemosensitizing drug selectively retained by neoplastic and reticuloendothelial tissues which, when exposed to a 630-nm argon laser, catalyzes a photochemical reaction to release free oxygen radicals, "the cytotoxic" agents responsible for cell death and tumor necrosis. Preliminary investigations have assessed the efficacy of photodynamic therapy in treatment of: (1) superficial "condemned mucosa" or "field cancerization" of the oral cavity and (2) stage III and IV head and neck carcinomas that had unsuccessful conventional therapy. Complete and/or partial remissions were obtained in 11 of 12 patients (16 treatments) with a variety of carcinomas of the nasopharynx, palate and uvula, retromolar trigone, temporal bone, cervical esophagus, and AIDS related Kaposi's sarcoma of the oral cavity. PMID- 2108408 TI - The effect of a leukotriene antagonist on the early response to antigen. AB - The sulfidopeptide leukotrienes (LT) C4, D4, and E4 increase in nasal secretions during the nasal response to antigen challenge, and nasal challenge with LTD4 induces nasal congestion. To further assess the role of leukotrienes, we administered an oral LTD4 antagonist, L-649,923, to 12 patients who had nasal allergy to grass and ragweed pollen, in a double-blind, placebo-controlled, crossover study. Patients were challenged intranasally with increasing doses of pollen on each of 2 days, and the recovered nasal lavage fluids were assayed for histamine, TAME-esterase activity, and immunoreactive LTC4/D4/E4. The patients graded runny nose, congestion, and throat irritation, and sneezes were counted. Significant (p less than 0.01) increases in all parameters were found when comparing antigen challenge with diluent challenge, but no differences were seen among the treatment groups. Thus, oral L-649,923 was not effective in blocking the symptoms of the early nasal allergic response. PMID- 2108410 TI - Abductor vocal cord spasm. AB - The purpose of this study is twofold. First, to introduce a new phenomenon- abductor vocal cord spasm, or abductor laryngospasm. Second, to reconcile a longstanding discrepancy involving the effect of lung inflation on vocal cord position. Abductor laryngospasm was induced in six anesthetized, tracheotomized dogs by the administration of continuous positive airway pressure (CPAP) after occlusion of the trachea for 60 seconds. Abductor laryngospasm was characterized by sustained vocal cord abduction with concomitant massive, continuous posterior cricoarytenoid muscle (PCA) electromyography (EMG) activity and little or no laryngeal adductor muscle EMG activity. Vocal cord opening was sustained for up to 90 seconds. In the same dogs, administration of CPAP, after hyperventilation of the animal, resulted in adductor laryngospasm. Adductor laryngospasm was characterized by steady apposition of the vocal cords, massive laryngeal adductor muscle EMG activity, and silent PCA EMG activity. Abductor laryngospasm appears to be the physiologic converse of adductor laryngospasm. The results of this study show that lung inflation can produce either vocal cord abduction or adduction, depending on whether the dog is hypoventilated or hyperventilated before administration of CPAP. PMID- 2108411 TI - Uvulopalatopharyngoplasty complications and avoidance strategies. AB - Reports of uvulopalatopharyngoplasty complications were elicited from 72 locations in the United States. We asked physicians to report all complications that had occurred in the 9 years since the operation was introduced. Sixteen fatalities were reported; respiratory distress was the most common cause. Forty six cases of nasopharyngeal stenosis were reported and 42 cases of palatal incompetence were reported. Hemorrhages and wound dehiscences were also reported. A retrospective analysis of the complications was made and diagnostic-therapeutic strategies are discussed with respect to prevention of complications. PMID- 2108412 TI - Surgical management of cholesteatoma in an only hearing ear. AB - The patient with a cholesteatoma in an only hearing ear presents a management dilemma: how best to treat the patient to minimize the chances of developing a severe hearing loss in that ear. Twelve patients managed surgically for cholesteatoma in their only hearing ear are reviewed. The location and extent of the cholesteatoma, the type of operation performed, and postoperative hearing results are presented. Eleven of the 12 patients maintained their bone-conducted speech reception threshold to within 5 dB of the preoperative level during follow up periods of 2 months to 4 years. Recommendations are made regarding preoperative evaluation, perioperative use of antibiotics and steroids, operative planning, ossicular reconstruction, and postoperative care. Special attention is given to the evaluation and management of the ear that has a fistula eroding into the cochlea and semicircular canals, both when suspected from preoperative imaging studies and when discovered intraoperatively. PMID- 2108413 TI - Soft tissue effects of the holmium-YSGG laser in the canine trachea. AB - A holmium-yttrium scandium gallium garnet laser is a pulsed mid-infrared crystalline laser (wavelength, 2.1 microns), which is easily transmissible through flexible quartz fibers. With use of a 300-microns fiber delivery system, this laser was applied in the canine trachea to create a standard 5-mm diameter lesion through mucosa and submucosa. Power settings of 400 mJ and 600 mJ per pulse at 2 pulses per second were used, and wound healing was studied over a 2 week period. Excellent control of depth of tissue ablation was noted, with uncomplicated wound repair. Although healing was somewhat slower compared with healing when the CO2 laser was used, less granulation and fewer inflammatory changes were noted. Further studies need to be performed to determine ideal laser dosimetry before this laser is applied clinically. PMID- 2108414 TI - Nerve sheath tumors of the paranasal sinuses: electron microscopy and histopathologic diagnosis. AB - Tumors of the nerve sheaths are very unusual. They occur with the highest frequency in the head and neck region, yet only 4% have been found to occur within the paranasal sinuses. Only 40 cases of nerve sheath tumors with direct involvement of the paranasal sinuses have been reported in the world's literature to date. Three new cases of neurofibroma not associated with Recklinghausen's disease and one case of a schwannoma of the frontoethmoid and maxillary sinuses are presented. The clinical, radiographic, and histopathologic features of these lesions will be discussed with emphasis on electron microscopy and immunohistochemical differentiation of these rare and often confusing lesions. PMID- 2108415 TI - Surgical management of chondroblastoma of the temporal bone. AB - Chondroblastoma of the skull is a benign but locally aggressive tumor. In the past, simple curettage and radiation therapy have been advocated for treatment of this tumor. We present two patients with chondroblastoma of the temporal bone. The tumor extended through the dura in both patients and into the temporal lobe in one patient. Both patients were treated with wide local excision using a combined extended transmastoid and middle cranial fossa approach. On the basis of these two cases and a review of the literature, we recommend complete surgical excision as the primary treatment for chondroblastoma of the temporal bone. PMID- 2108416 TI - Intraoperative facial nerve monitoring. Technical aspects. AB - Intraoperative facial nerve monitoring (FNM) is widely used as a method of assessing the anatomic and physiologic integrity of the facial nerve during procedures in which the nerve may be in jeopardy. The doctors of the Otologic Medical Group use intraoperative FNM during all neurotologic procedures. This technique can also be used for congenital ear surgery and complicated revision chronic ear surgery. On the basis of experience gained from more than 200 cases in which FNM has been used, definitive conclusions can be made in regard to technical aspects. This article will discuss indications for intraoperative FNM, electrode design, visual and auditory feedback, and the particulars about stimulators. PMID- 2108417 TI - Nasal endoscopic control of epistaxis--a preliminary report. PMID- 2108418 TI - Osteosarcoma of the soft tissue of the larynx: report of a case with electron microscopic studies. PMID- 2108419 TI - Dermatopathic lymphadenopathy presenting as a parotid mass. PMID- 2108420 TI - Otogenic skull base osteomyelitis caused by invasive fungal infection. PMID- 2108421 TI - Pasteurella multocida otitis media complicated by facial palsy. PMID- 2108422 TI - Otolaryngologic manifestations of pregnancy. PMID- 2108423 TI - Improved mechanical therapeutic nasal dilator to treat nasal airway obstruction. PMID- 2108424 TI - Antigenicity of adult Schistosoma mansoni alkaline phosphatase. AB - Antibodies to the alkaline phosphatase (AP) of Schistosoma mansoni in infected human and mice sera were evaluated by a direct solid-phase AP immunoadsorption assay (APIA) and by Western blot and immunostaining. APIA consisted of (a) solid phase capture of immunoglobulins from infected human or mice, (b) immunoadsorption of the enzyme antigen by the antibodies, and (c) detection of the enzymatic activity. By this procedure the appearance of the anti-AP response in mice was detected around 50 days post-infection; this response was not specific for an AP of a given schistosome strain and it was not induced by an autoimmunity phenomenon. Fourteen out of 15 sera from infected people tested by APIA showed a clear antibody response against this enzyme. Immunoblots in non reducing conditions supported APIA results indicating that the parasite AP was specifically recognized by the antibodies present in infected human and mice sera. These results suggest the possible usefulness of the schistosome AP as a marker for S. mansoni infection. PMID- 2108425 TI - Pulsatile secretion of LH and FSH in prepubertal and early pubertal boys revealed by ultrasensitive time-resolved immunofluorometric assays. AB - Pulsatile secretion of LH and FSH was examined in 10 prepubertal (aged 4.5-12.9 y) and seven early pubertal (aged 12.8-14.5 y) boys with ultrasensitive (0.019 and 0.014 IU/L) time-resolved immunofluorometric assays. Plasma LH and FSH levels were measured every 15 or 20 min for 6 h during the day and night. The lowest mean LH level in a prepubertal boy was 0.02 IU/L and in eight other prepubertal boys mean LH levels were less than 0.4 IU/L. In early pubertal boys the mean LH levels ranged from 0.3 to 6.5 IU/L. The difference in mean FSH level between prepubertal (0.61 IU/L) and early pubertal boys (1.85 IU/L) was smaller than the difference in LH level. All boys had significant LH and FSH pulses. The LH interpulse interval was 135 +/- 86 min (mean +/- SD) and 76 +/- 65 min for the prepubertal and pubertal boys, respectively (p less than 0.01). For FSH, the respective values were 150 +/- 122 and 221 +/- 157 min (p = NS). The mean LH pulse amplitudes were 11-fold greater in the early pubertal boys than in the prepubertal boys, whereas the mean FSH pulse amplitudes were similar between the two groups. The present method shows that the mean LH levels in prepubertal boys are much lower, and the increase during puberty larger, than previously reported. The increase is apparently due to increased pulse frequency and amplitude. The increase in mean FSH level is smaller and evidently not caused by an increase in pulse frequency or pulse amplitude. PMID- 2108426 TI - Impact of refeeding on intestinal development and function in infant rabbits subjected to protein-energy malnutrition. AB - The impact of early postnatal protein-energy malnutrition and of 4, 7, and 14 d of nutritional rehabilitation on small intestinal growth, development, structure and function was examined in 28-, 32-, 35-, and 42-d-old infant rabbits. Malnutrition was induced by litter expansion 7 d postpartum and, in randomly selected malnourished animals, refeeding was begun at weaning, 28 d. Results are compared to ad libitum fed dietary controls. Malnutrition altered the small intestine of the developing rabbit, as evidenced by: 1) reduced jejunal and ileal mass as shown by decreased mucosal wt, protein, and DNA content; 2) depressed epithelial proliferation and enterocyte migration along the crypt-villus axis; 3) delayed epithelial maturation as measured by mucosal enzyme activities; and 4) enhanced glucose-stimulated Na+ transport. Refeeding stimulated rapid and complete recovery, as evidenced by: 1) restoration of jejunal and ileal mucosal mass within 4 d; 2) enhancement of epithelial renewal and enterocyte migration by 7 d; and 3) complete return of the normal pattern of mucosal enzymes by 14 d. With 7 d of refeeding, glucose-stimulated Na+ transport was down-regulated to the level of dietary controls. We conclude that early postnatal protein-energy malnutrition has a severe impact on small intestinal growth, development, structure, and function. Furthermore, a brief period refeeding induced a rapid and complete recovery of these parameters. PMID- 2108427 TI - Political changes affect NM long term care facilities. PMID- 2108428 TI - Tension surrounds survey process in LTC facilities. PMID- 2108429 TI - The cyanelle genome of Cyanophora paradoxa, unlike the chloroplast genome, codes for the ribosomal L3 protein. AB - We describe a 1132 bp sequence of the cyanelle genome of Cyanophora paradoxa containing the rpl3 gene. This gene, which is not chloroplast encoded in plants, is the first of a long cyanelle ribosomal operon whose organization resembles that of the S10 operon of E. coli. We have shown that the rpl3 gene is transcribed in cyanelles as a 7500 nucleotide precursor and that the 5'-end of the mRNA starts approximately 90 nucleotides upstream from the initiation codon. However, no typical procaryotic promoter could be found for this gene. We have detected, using anti E. coli L3 antibodies, the cyanelle L3 protein in cyanelle extracts and in E. coli cells transformed with the cyanelle rpl3 gene. PMID- 2108430 TI - Circular chromosomal DNA in the sulfur-dependent archaebacterium Sulfolobus acidocaldarius. AB - The shape of the chromosomal DNA of the sulfur-dependent archaebacterium Sulfolobus acidocaldarius was analyzed by the pulsed-field gel electrophoresis(PFGE). S.acidocaldarius DNA digested with Notl showed two DNA bands at around 1.0 Mbp and 2.1 Mbp. Notl-linking clones were isolated from the library of S.acidocaldarius chromosomal DNA. It contained two Notl sites. Both 1.0 and 2.1 Mbp DNA band separated by PFGE were hybridized with the two independent Notl-linking fragment. Each right and left arms of two Notl-linking fragments were hybridized with one of the two DNA bands separated by PFGE. The results indicated that the chromosomal DNA of S.acidocaldarius is circular. PMID- 2108431 TI - Nucleotide sequence of the psbK gene of the cyanobacterium Synechocystis 6803. PMID- 2108432 TI - Nucleotide sequence of a Bacillus subtilis gene homologous to the grpE gene of E. coli located immediately upstream of the dnaK gene. PMID- 2108433 TI - DNA sequence of exoenzyme C3, an ADP-ribosyltransferase encoded by Clostridium botulinum C and D phages. PMID- 2108434 TI - Transient prealbumin-associated hyperthyroxinemia in TSH-producing pituitary adenoma. AB - This case report describes a 38-year-old male who was hospitalized for further clarification of clinically mild hyperthyroidism. His increased total hormone levels, the elevated free thyroid hormones and the elevated basal TSH with blunted response to TRH strongly suggested a pituitary adenoma with inappropriate TSH incretion. Transmission computed tomography showed an intrasellar expansion, 16 mm in diameter. The neoplastic TSH production was confirmed by an elevated alpha-subunit and a raised molar alpha-sub/TSH ratio. However, T4 distribution on prealbumin (PA, TTR), albumin (A) and thyroxine binding globulin (TBG) showed a clearly increased binding to PA (39%), indicating additional prealbumin associated hyperthyroxinemia. The absolute values of PA, A and TBG were within the normal range. After removal of the TSH-producing adenoma, basal TSH, the free thyroid hormones and T4 binding to prealbumin returned to normal. Therefore, the prealbumin-associated hyperthyroxinemia had to be interpreted as a transitory phenomenon related to secondary hyperthyroidism (T4 shift from thyroxine binding globulin to prealbumin) rather than a genetically conditioned anomaly of protein binding. PMID- 2108435 TI - Pre-operative nutritional assessment. PMID- 2108436 TI - Nutrition. Giving choices. PMID- 2108437 TI - Someone has to 'close the checkbook'. Medicaid costs are doubling every 7 years! PMID- 2108438 TI - Effect of methionine and lysine deficiencies on protein synthesis in the liver and oviduct and in the whole body of laying hens. AB - For laying hens, protein synthesis in the liver, in the oviduct (magnum and remaining portions), and in the whole body was measured in vivo in order to investigate the effect of a dietary deficiency of methionine or lysine. The rate of protein synthesis in tissues was calculated from the incorporation of L [15N]phenylalanine into the protein fraction; whole-body protein synthesis was estimated from the plateau enrichment of free [15N]phenylalanine in plasma. The enrichment of labeled phenylalanine was analyzed by using a gas-chromatograph mass spectrometer, following a primed infusion of the isotope for 6 h. The whole body protein synthesis of laying hens fed diets deficient in amino acids was significantly lower than that of control hens. Protein synthesis in the liver, magnum, and remainder of the oviduct was decreased by a dietary deficiency of the amino acids studied with larger rates of decrease than for the whole-body analysis. The proportion of reduction in protein synthesis resulting from the sum of the tissues studied, compared with that of the whole body, was 36 and 50%, respectively, for a deficiency of methionine and lysine. PMID- 2108439 TI - Antibodies to a histidine-rich protein (PfHRP1) disrupt spontaneously formed Plasmodium falciparum erythrocyte rosettes. AB - Cerebral involvement in Plasmodium falciparum malaria is associated with sequestration of infected red blood cells and occlusion of cerebral vessels. Adhesion of infected erythrocytes along the vascular endothelium as well as binding of uninfected erythrocytes to cells infected with late-stage asexual parasites (rosetting) may be important in erythrocyte sequestration. We report that the recently discovered rosetting phenomenon shares characteristics with other human cell-cell interactions (heparin sensitivity, temperature independence, Ca2+/Mg2+ and pH dependence). Mono- and polyclonal antibodies specific for PfHRP1, a histidine-rich protein present in the membrane of P. falciparum-infected erythrocytes, disrupt rosettes but do not affect attachment of infected erythrocytes to endothelial cells. The inhibitory anti-PfHRP1 antibodies reacted with rosetting parasites in indirect immunofluorescence and with P. falciparum polypeptides of Mr 28,000 and Mr 90,000 in immunoprecipitation and immunoblotting, respectively. No inhibitory effects on erythrocyte rosetting were obtained with antibodies to related histidine-rich or other antigens of P. lophurae or P. falciparum. Whether the epitope that mediates rosetting, and is recognized by the anti-PfHRP1 antibodies, is located on PfHRP1 or on a crossreactive antigen remains to be established. The results suggest that endothelial cytoadherence and erythrocyte rosetting involve different molecular mechanisms. PMID- 2108440 TI - Two pharmacologically distinct sodium- and chloride-coupled high-affinity gamma aminobutyric acid transporters are present in plasma membrane vesicles and reconstituted preparations from rat brain. AB - Electrogenic sodium- and chloride-dependent gamma-aminobutyric acid (GABA) transport in crude synaptosomal membrane vesicles is partly inhibited by saturating levels of either of the substrate analogues cis-3 aminocyclohexanecarboxylic acid (ACHC) or beta-alanine. However, both of them together potently and fully inhibit the process. Transport of beta-alanine, which exhibits an apparent Km of about 44 microM, is also electrogenic and sodium and chloride dependent and competitively inhibited by GABA with a Ki of about 3 microM. This value is very similar to the Km of 2-4 microM found for GABA transport. On the other hand, ACHC does not inhibit beta-alanine transport at all. Upon solubilization of the membrane proteins with cholate and fractionation with ammonium sulfate, a fraction is obtained which upon reconstitution into proteoliposomes exhibits 4- to 10-fold-increased GABA transport. This activity is fully inhibited by low concentrations of ACHC and is not sensitive at all to beta alanine. GABA transport in this preparation exhibits an apparent Km of about 2.5 microM and it is competitively inhibited by ACHC (Ki approximately 7 microM). These data indicate the presence of two GABA transporter subtypes in the membrane vesicles: the A type, sensitive to ACHC, and the B type, sensitive to beta alanine. PMID- 2108441 TI - Epithelial glycoprotein is a member of a family of epithelial cell surface antigens homologous to nidogen, a matrix adhesion protein. AB - The cell surface antigen, epithelial glycoprotein, defined by the monoclonal antibody HEA 125, is expressed on virtually all epithelial cell membranes but not on mesodermal or neural cell membranes. The cDNA encoding epithelial glycoprotein was isolated by HEA 125 antibody enrichment of colon tumor cDNA expressed transiently in COS cells. The sequence of the epithelial glycoprotein antigen is identical to the cell membrane protein recognized by the monoclonal antibody KS 1/4 and is homologous to the tumor-associated antigen GA733. These proteins share sequence homology to nidogen, an extracellular matrix component that appears to participate in cell-matrix adhesion. These proteins also share a homologous domain found in the B1 chain of laminin, a matrix adhesion protein, and placental protein 12, an insulin-like growth factor I binding protein secreted during pregnancy that has been implicated in regulation of fetal growth. This common domain is also repeated multiple times within the thyroglobulin precursor. These findings suggest epithelial glycoprotein is a cell surface molecule involved in cell-cell or cell-matrix interaction. PMID- 2108442 TI - Fetal IgG specificities against Trypanosoma cruzi antigens in infected newborns. AB - A panel of Trypanosoma cruzi antigens produced by recombinant DNA techniques was used to analyze the IgM and IgG specificities present in sera from 22 mothers with chronic Chagas disease and their newborn infants. Ten of the newborns were congenitally infected and the other 12 children were healthy. While in most cases IgG specificities in the newborns mirrored those of their mothers, congenitally infected newborns had, in addition, IgG specificities that were undetectable in their mothers. The new IgG specificities observed most frequently were against a shed acute-phase antigen (SAPA), and less frequently, against other nine different parasite antigens. Thus, SAPA is able to identify new fetal IgGs because antibodies against this antigen are generated during the acute phase of the infection and not in their chronically infected mothers. Sera from congenital cases also had IgMs against several parasite antigens, but again, SAPA was the most frequently detected. Neither IgMs nor new IgG specificities were detected in healthy children born to mothers with Chagas disease. We conclude that individual antigens can be used to detect new IgG specificities present in the cord blood from infected newborns. Furthermore, detection of IgMs and new fetal IgGs with recombinant antigens may be used to sort out congenitally infected infants from uninfected ones, a method that might be applied to other infectious diseases. PMID- 2108443 TI - Age-related modulatory activity by a cholinergic agonist on the growth hormone response to GH-releasing hormone in the rat. AB - The involvement of the cholinergic system in growth hormone (GH) secretion has acquired increased importance in the last few years. In rats, pretreatment with muscarinic cholinergic agonists potentiates the GH release induced by GH releasing hormone (GHRH), via inhibition of somatostatin (SRIF) release from the hypothalamus. The aim of this study was to validate the use of cholinergic agonists to probe the functional activity of the hypothalamic SRIF system. It is known that hypothalamic SRIF displays an age-related increase in its functional activity; therefore, rats from 10 days to 29 months of age were used and challenged with GHRH following acute administration of pilocarpine, a cholinergic muscarinic agonist. Following administration of GHRH alone there was an age related decline in GH responsiveness. Administration of pilocarpine potentiated the GH response to GHRH during the entire life-span of the rats, the only exception being 10-day-old rats in which the drug was without effect. Pilocarpine, though effective in potentiating the GH response to GHRH, did not restore, in senescent rats, GH stimulation to the level of that present in young (3-month old) or adult rats (8-month old). However, the drug was effective in rejuvenating the GH response to GHRH of the older rats (29- and 18-month old) to the level of 15-month-old rats. The present results indicate that modulation of the GH response to GHRH by pilocarpine is consonant with the known changes in the activity of hypothalamic SRIF. Cholinergic drugs may therefore represent a valuable tool to assess SRIF function in physiologic or pathologic conditions of GH secretion, and, in addition, to potentiate GH release during a course of GHRH therapy. PMID- 2108444 TI - Heparin-sensitive inositol trisphosphate signaling and the role of G-proteins in Ca2(+)-release and contractile regulation in smooth muscle. PMID- 2108445 TI - Modulators of myosin light chain kinase activity affect both [Ca+2] and contraction in single smooth muscle cells. PMID- 2108446 TI - The role of elevated intracellular calcium in the susceptibility to ventricular fibrillation. PMID- 2108447 TI - Methyl beta-carboline-3-carboxylate enhances performance in a multiple-trial learning task in mice. AB - In contrast to diazepam, a benzodiazepine receptor (BZ-R) ligand, which impairs memory processing, methyl beta-carboline-3-carboxylate (beta-CCM), another BZ-R ligand, administered before a training session, enhances performance in a retention test. This action, however, has only been demonstrated in single trial or single session learning protocols. The present report extends these results to a multiple-trial learning procedure in mice (brightness discrimination in a T maze with negative reinforcement). The animals were trained for sessions of ten trials per day for six consecutive days. In a first experiment, the sessions during the first three days took place after administration of beta-CCM (0.3 mg/kg), diazepam (2.5 mg/kg) or saline. In a second experiment, especially designed to study the effects of beta-CCM, during the first three days animals received beta-CCM (0.3 mg/kg), Ro 15-1788 (15 mg/kg), beta-CCM + Ro 15-1788, vehicles of these drugs or saline. In the first experiment, performance was improved by beta-CCM and impaired by diazepam in the first three sessions as well as in the final three. In the second experiment, beta-CCM alone, as well as Ro 15 1788 improved performance, and the simultaneous administration of the two drugs suppressed these effects. These results suggest that the performance enhancing effects of beta-CCM observed in single trial learning protocols, during the retention test, can already be observed during drug treatment. They confirm that beta-CCM has an action on acquisition (learning). As the effects of beta-CCM are suppressed by the simultaneous administration of Ro 15-1788, our results could suggest a role for benzodiazepine receptors in learning. This question is discussed. PMID- 2108448 TI - The effects of flumazenil-precipitated abstinence on the pharmacokinetics of chronic oxazepam in dogs. AB - The pharmacokinetics of oxazepam was studied in naive dogs and in oxazepam dependent dogs without and with administered flumazenil (6 mg/kg). Oxazepam is eliminated with a relatively short elimination half life (ca. 150 min) in both acutely and chronically treated dogs. It exhibits only a modest first pass metabolism (ca. 10%) and its bioavailability following oral administration is about 22%. The steady state concentration of oxazepam in chronically treated dogs was lower than was predicted from single dose studies. Flumazenil did not change the rate of absorption or elimination of oxazepam-dependent dogs. The total steady state plasma concentration of oxazepam was significantly reduced by flumazenil administration suggesting a displacement interaction between flumazenil and oxazepam. PMID- 2108449 TI - Partial cross-dependence on ethanol in mice dependent on chlordiazepoxide. AB - Mice which had been fed chronically a liquid diet containing chlordiazepoxide (CDP) showed spontaneous and Ro15-1788-induced withdrawal signs upon CDP withdrawal. Ethanol (1.5 g/kg) injected 5 min before Ro15-1788 injection almost completely suppressed the withdrawal signs induced by the benzodiazepine receptor antagonist. However, neither ethanol injection nor ethanol diet administration could prevent the loss of appetite and weight loss on day 1 of CDP withdrawal. Likewise, the addition of saccharin in the ethanol diets did not prevent the loss of appetite. Mice which had been fed the CDP diet followed by 9 days of ethanol treatment (CDP/ethanol) showed more severe hypothermia during ethanol withdrawal compared to mice which had been fed the control/ethanol diets. The CDP/ethanol mice also retained the increase in runway activity attained from the prior CDP treatment. The data indicate that CDP-dependent mice showed partial rather than full cross-dependence on ethanol. PMID- 2108450 TI - Leukotrienes and inflammation. AB - The leukotrienes are synthesized from essential fatty acids via a 5-lipoxygenase enzyme. Most is known about the four-series leukotrienes derived from arachidonic acid. Leukotriene B4 is a potent chemotactic agent for leukocytes and it induces neutrophil-dependent increased microvascular permeability. Leukotrienes C4, D4 and E4 are bronchoconstrictors; and potent mediators of microvascular tone and permeability. The leukotrienes have been suggested to have a role in many inflammatory conditions in man in the skin (e.g. psoriasis), the lung (e.g. allergic asthma), joints (e.g. rheumatoid arthritis) and in the heart (e.g. myocardial infarction). Drugs which inhibit the generation and the actions of leukotrienes are under development and are being tested clinically as potential anti-inflammatory agents. PMID- 2108451 TI - Metabolism and action of amino acid analog anti-cancer agents. AB - The preclinical pharmacology, antitumor activity and toxicity of seven of the more important amino acid analogs, with antineoplastic activity, is discussed in this review. Three of these compounds are antagonists of L-glutamine: acivicin, DON and azaserine; and two are analogs of L-aspartic acid: PALA and L-alanosine. All five of these antimetabolites interrupt cellular nucleotide synthesis and thereby halt the formation of DNA and/or RNA in the tumor cell. The remaining two compounds, buthionine sulfoximine and difluoromethylornithine, are inhibitors of glutathione and polyamine synthesis, respectively, with limited intrinsic antitumor activity; however, because of their powerful biochemical actions and their low systemic toxicities, they are being evaluated as chemotherapeutic adjuncts to or modulators of other more toxic antineoplastic agents. PMID- 2108452 TI - Moral and ethical issues in elder care. PMID- 2108453 TI - Interaction between antidepressants and d-amphetamine on variable-interval performance. AB - Four experiments were carried out investigating the interactions between some antidepressant drugs (imipramine, desipramine, fluvoxamine, trazodone (4 and 8 mg/kg) and d-amphetamine (0.1-3.2 mg/kg) on operant behaviour maintained under a variable-interval 80-s schedule of sucrose reinforcement; each experiment employed 12 rats. d-Amphetamine exerted a dose-related suppressant effect on response rate. Imipramine and desipramine given alone had no effect on response rate, whereas fluvoxamine (both doses) and the higher dose of trazodone produced significant increases in response rate. Pretreatment with imipramine, desipiramine or fluvoxamine significantly potentiated the suppressant effect of d amphetamine on responding; pretreatment with trazodone had no significant effect. The potentiating effect of imipramine and desipramine may be related to their well known uptake blocking actions. The fact that fluvoxamine, a selective inhibitor of 5-hydroxytryptamine (5HT) uptake, also potentiated the effect of d amphetamine suggests that the suppressant effect of d-amphetamine on operant behaviour may involve 5HT as well as catecholamine release. The lack of effect of trazodone may reflect its failure to influence uptake mechanisms. On the basis of a formal model couched in terms of Herrnstein's (1970) equation, it is suggested that imipramine, desipramine and fluvoxamine may have enhanced d-amphetamine's ability to reduce response capacity; it is suggested that the data do not provide evidence for an interaction between the antidepressants and the putative "motivation-enhancing" effect of d-amphetamine. PMID- 2108454 TI - The sentinel HIV seroprevalence surveys. PMID- 2108455 TI - HIV seroprevalence surveys in sexually transmitted disease clinics. AB - The Centers for Disease Control, in cooperation with State and local health departments, is conducting human immunodeficiency virus, type 1 (HIV), seroprevalence surveys, using standard protocols, in sexually transmitted disease (STD) clinics in selected metropolitan areas throughout the United States. The surveys are blinded (serologic test results not identified with a person) as well as nonblinded (clients voluntarily agreeing to participate). STD clinics are important sentinel sites for the surveillance of HIV infection because they serve persons who are at increased risk as a result of certain behaviors, such as unprotected sex, homosexual exposure, or intravenous drug use. HIV seroprevalence rates will be obtained in the sentinel clinics each year so that trends in infection can be assessed over an extended period of time. Behaviors that place clients at risk for infection, or protect against infection, are being evaluated in voluntary, nonblinded surveys to define groups for appropriate interventions and to detect changes in response to education and prevention programs. Although inferences drawn from the surveys are limited by the scope of the clinics and clients surveyed, HIV trends in STD clinic client populations should provide a sensitive monitor of the course of the acquired immunodeficiency syndrome (AIDS) epidemic among persons engaging in high-risk sexual behaviors. PMID- 2108456 TI - HIV seroprevalence surveys in drug treatment centers. AB - Sharing of equipment used to inject illicit drugs intravenously is a risk factor for human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). Systematic surveillance of HIV infection among intravenous drug users (IVDUs) in the United States is essential to monitor the HIV epidemic and to target and evaluate prevention programs for IVDUs and their partners. The most accessible segment of the largely covert population of IVDUs are those in drug treatment programs. In collaboration with State and local health departments and drug abuse treatment agencies, the Centers for Disease Control is conducting blinded (serologic test results not linked to identifiable persons) and nonblinded (in which clients voluntarily agree to participate) surveys of IVDUs entering drug treatment in 39 U.S. metropolitan areas. The same protocol is used in all participating drug treatment centers. Blinded surveys will be carried out annually to determine HIV seroprevalence rates in eligible IVDUs entering drug treatment and to monitor trends over time. Each year, nonblinded surveys of IVDUs entering drug treatment will assess self-reported drug use and sexual behaviors to help design educational interventions and to detect changes in behavior over time. This sentinel surveillance system, using a standardized methodology, will provide the best national and regional data available on the seroprevalence of HIV among IVDUs and the relationships of drug use, sexual behaviors, and HIV serologic status of IVDUs. PMID- 2108457 TI - Determining HIV seroprevalence among women in women's health clinics. AB - Human immunodeficiency virus, type 1 (HIV), seroprevalence studies are needed to determine the level and trends of HIV infection among women attending family planning, abortion, and prenatal care clinics in the United States. A review of published and unpublished studies showed that HIV seroprevalence among women attending women's health clinics was 0 to 2.6 percent, although the studies were difficult to compare because of differences in methodology. The Centers for Disease Control, in association with State and local health departments, has developed a standardized protocol to determine HIV seroprevalence among women attending women's health clinics in selected metropolitan areas. Blinded HIV serosurveys (serologic test results not identified with a person) are being conducted annually in selected sentinel clinics in order to obtain estimates of HIV seroprevalence unbiased by self-selection, as well as to monitor trends in infection among clients attending these clinics. In areas with high HIV seroprevalence, nonblinded serosurveys (in which clients voluntarily agree to participate) will be used to assess behaviors that may place women at increased risk of exposure to HIV. Data from the surveys can be used in developing age specific and culturally appropriate AIDS educational materials, assessing the amount and type of counseling activities required, and evaluating acquired immunodeficiency syndrome (AIDS) prevention activities. The information will provide epidemiologic data to complement the results of other surveys in characterizing the scope of HIV infection among women of childbearing age in the United States. PMID- 2108458 TI - Estimating HIV levels and trends among patients of tuberculosis clinics. AB - Symptomatic tuberculosis (TB) can occur as an opportunistic disease in immunosuppressed persons who are infected with human immunodeficiency virus (HIV) and who have been previously infected with Mycobacterium tuberculosis. Increases in TB cases have occurred in areas which have reported large numbers of cases of the acquired immunodeficiency syndrome (AIDS), and a high proportion of these TB cases have been HIV seropositive. Therefore, increasing numbers of HIV-infected persons may be found in TB clinics and hospitals. HIV serologic surveys in TB clinics and hospitals providing clinical services to TB patients are needed to assess the local prevalence of HIV infection in TB patients and the consequent need for public health intervention to prevent further spread of HIV and TB infection. The Centers for Disease Control (CDC), in collaboration with State and local health departments, has initiated HIV surveillance of patients with confirmed and suspected TB in TB clinics and hospitals in the United States. Blinded (serologic test results not linked to identifiable persons) HIV seroprevalence surveys are conducted in sentinel TB clinics and hospitals that provide TB clinical services each year to obtain estimates of the level of HIV infection in TB patients and to follow trends in infection over time. Nonblinded (voluntary) surveys will also be conducted to evaluate behaviors that have placed TB patients at risk for or protected them against HIV infection. Data from these surveys will be used to target education and prevention and control programs for TB and HIV infection and to monitor changes in behavior in response to such programs. PMID- 2108459 TI - Methods of surveillance for HIV infection at U.S. sentinel hospitals. AB - The U.S. sentinel hospital surveillance system for human immunodeficiency virus (HIV) infection includes approximately 40 short-stay hospitals located in 31 metropolitan areas in the United States and Puerto Rico. Several hospitals began testing in late 1986, and additional sentinel hospitals have since been recruited. At each sentinel hospital, anonymous, unlinked testing for antibody to HIV is conducted monthly on 300 blood specimens, selected systematically and stratified by age of the patient. Specimens are excluded from patients whose reason for hospital visit on that occasion was for a medical condition associated with HIV infection or with risk factors for HIV infection, in order to limit the expected overrepresentation of HIV-infected persons among hospital patients compared with the general catchment population of the hospital. The incidence of acquired immunodeficiency syndrome (AIDS) in metropolitan areas with sentinel hospitals has been approximately twice the incidence of AIDS in the entire United States. However, while absolute levels of HIV seroprevalence should therefore be interpreted with caution, trends in the age-, sex-, and race-specific HIV seroprevalence at sentinel hospitals likely reflect trends in the communities served by the hospitals. Although concentrated in areas disproportionately affected by AIDS, sentinel hospitals will contribute seroprevalence data over time that reflect the impact of HIV infection across all age and behavioral risk groups. Sentinel hospitals will also constitute a key surveillance system to help integrate the age group-specific and risk group-specific findings from other activities in the CDC family of seroprevalence surveys. PMID- 2108460 TI - HIV seroprevalence surveys of childbearing women--objectives, methods, and uses of the data. AB - A seroprevalence survey of human immunodeficiency virus (HIV) among childbearing women is being conducted in 43 States and Territories as one of the family of HIV seroprevalence surveys. This blinded survey, in which serologic test results are not linked to identifiable persons, uses neonatal dried blood specimens on filter paper to test for maternal antibodies to HIV. This survey provides relatively unbiased estimates of prevalence of HIV infection in the population of women delivering live children during given survey periods, by month or quarter of delivery, geographic area, and demographic subgroup. This objective will be met while protecting the integrity and efficient conduct of neonatal screening programs and ensuring patient anonymity. Information from this survey will be used to (a) assess the levels and trends of HIV infection in women and infants, (b) help develop and evaluate prevention programs, and (c) project the number of women and children who will develop HIV infection and the acquired immunodeficiency syndrome (AIDS) and will require health care and social services in the future. PMID- 2108461 TI - Methodologic approaches to surveillance of HIV infection among blood donors. AB - Blood donors make up the largest group in the United States that is tested for human immunodeficiency virus, type 1 (HIV) antibody. The blood donor population is ideal for detecting and quantifying uncommon or unrecognized modes of HIV transmission in the general population because persons at known risk for HIV infection are excluded from donating blood. The national HIV surveillance program consists of a centralized computer database of information on all donations at selected American Red Cross blood centers, which together account for about a quarter of the blood supply, and all donations at 20 regional blood centers where seropositive blood donors are interviewed to evaluate their risk factors for HIV infection and to determine their epidemiologic characteristics and motives for donation. Trends in HIV prevalence and incidence within specific demographic subgroups are determined for first-time and repeat donors. Combining the trends with HIV-risk profile data from seropositive donors provides a rate for HIV seropositive donors with no identified risk. Epidemiologic and behavioral data from seropositive donors will help in the development and evaluation of future donor deferral strategies. PMID- 2108462 TI - Methods of surveillance for HIV infection in primary care outpatients in the United States. AB - Primary care outpatients provide a good sentinel population for monitoring levels and trends of HIV infection in the United States. Because a broad cross section of the population seeks primary medical care, excess blood from specimens routinely collected for other purposes is available for anonymous, unlinked HIV testing, and all age groups and both sexes can be sampled. The CDC family of surveys includes two surveys of primary care outpatients: (a) a survey of 100,000 blood specimens per year submitted by more than 6,000 primary care physicians to a national diagnostic laboratory for complete blood count or hematocrit and (b) a survey of approximately 10,000 blood specimens per year from a network of 242 primary care physicians. Each survey has different advantages: the laboratory based survey has a large sample from a large population base, and the physician network survey has a well-defined patient population in which each patient's clinical condition can be determined. In the primary care physician network, a concurrent study of clinical patterns of disease in patients with recognized HIV infection provides additional information on the clinical syndromes associated with HIV infection and estimates of the occurrence of unrecognized HIV infection. PMID- 2108463 TI - Using seroprevalence data in managing public health programs. AB - An objective of the Centers for Disease Control (CDC) family of HIV seroprevalence surveys, conducted by State and local health departments, is the collection of seroprevalence data that may be useful in managing public health programs. In prevention programs, seroprevalence data may be used in allocating resources, in determining the types and amount of education, counseling, and testing services offered, and in identifying access points for HIV-infected persons for medical followup and care. Over time, data will be useful in detecting and following trends in HIV infection and in evaluating the impact of program activities to prevent HIV infection. No single seroprevalence survey is representative of the entire population of a metropolitan area. Each type of survey has strengths and limitations that must be considered when interpreting seroprevalence data. However, results from the family of surveys are the best available data because they are relatively unaffected by self-selection bias, they are standardized, and the information is collected over time. Characterization of the population surveyed and adherence to standard CDC protocols improve the quality of the data. Consultants in health departments and at CDC form a network for providing technical support and disseminating data to health care providers and program managers. PMID- 2108464 TI - Massachusetts' post-traumatic stress disorder program: a public health treatment model for Vietnam veterans. AB - Post-traumatic stress disorder (PTSD) can be a serious aftermath of catastrophic events such as war. The incidence of PTSD appears to be high among Vietnam veterans. PTSD can be extremely disruptive to a person's physical and mental well being, family life, social relationships, and employment status. Yet, for a variety of reasons, many Vietnam veterans suffering from PTSD have remained undiagnosed or insufficiently treated. The Massachusetts Department of Public Health, in cooperation with the Massachusetts Department of Veterans Services, initiated a hospital-based treatment and rehabilitation program for Vietnam veterans who have PTSD. As of November 1989, 150 Vietnam veterans had been admitted to this program. PMID- 2108465 TI - Distance between homes and exercise facilities related to frequency of exercise among San Diego residents. AB - Although personal determinants of exercise behavior have been studied extensively, few investigators have examined the influence of the physical environment on exercise habits. A random sample of 2,053 residents of San Diego, CA, were surveyed regarding exercise habits and other variables. A total of 385 exercise facilities in San Diego were classified into categories of either free or pay. After the addresses of respondents and facilities were located on a grid map and coded, the density of exercise facilities around each respondent's home address was computed. Subjects who reported engaging in three or more exercise sessions per week reported a statistically greater density of pay facilities near their homes than did those who reported no exercise sessions, after controlling for age, education, and income. The finding suggests an association between proximity of exercise facilities and frequency of exercise. PMID- 2108466 TI - Public concern about chemicals in the environment: regional differences based on threat potential. AB - While the hazards of chronic environmental pollution remain unclear, people are making decisions about their exposure to pollution and its possible effects on their health. To compare people's concerns about environmental problems, a systematic, stratified sample was surveyed. The sample was made up of residents, ages 25 through 74 years, of three areas of New York State. The three areas were western New York, with a high density of toxic dump sites; Long Island, with a major shallow ground water aquifer; and the remainder of the State, excluding New York City, as a comparison area. The sampling list was obtained from records of licensed drivers of the New York State Department of Motor Vehicles. A 66 percent response rate was obtained to the mailed survey. As expected, most concerns were greater for western New York and Long Island, the two areas with highest threat potential for exposure or contamination, than for the comparison area. The single exception was that no regional differences were noted for concerns about environmental pollution and contamination. All concerns were associated with perceived distance between one's residence and a source of potential exposure. Regardless of region, women were more concerned than men about exposures, pollution, and related health effects. No sex differences, however, were noted for economic concerns. PMID- 2108467 TI - Smokeless tobacco use among Native American school children. AB - Seven published and two unpublished surveys of Native American school children's use of smokeless tobacco (ST) are reviewed. The surveys represent school children in the States of South Dakota, Montana, Nebraska, Washington, Arizona, New Mexico, and Alaska. This review describes and discusses the survey methods, prevalence, duration, and intensity of ST use, and ST health effects documented in these studies. Prevalence of regular ST use ranges from 18 percent in kindergartners through 6th graders to 55.9 percent among 9th and 10th graders. In two studies that surveyed kindergartners, regular use was reported at 13 percent in one study and 21 percent in the other. Comparisons to use by non-Native Americans, as reported in surveys, demonstrate the severity of the problem in Native American communities. There appear to be three significant findings related to Native American ST use: (a) young age of onset of ST use, (b) similar prevalence of use among adolescent boys and girls, and (c) higher overall prevalence of ST use when compared to non-Native American populations. Acceptance of the habit, peer pressure, and addiction seem to be contributing to the high ST use in Native American communities. PMID- 2108469 TI - Kidney and lung injury in irradiated rats protected from acute death by partial body shielding. AB - Ninety-six CD-1 male rats were exposed to gamma-ray doses (0-25 Gy) in increments of 5 Gy. One femur, the surgically exteriorized GI tract, and the oral cavity were shielded during irradiation to protect against acute mortality from injury to the hematopoietic system, small intestine, and oral cavity. In addition, the thoraxes of half of the animals from each dose group were shielded. At approximately monthly intervals from 2 to 10 months after irradiation the hematocrit, plasma urea nitrogen (PUN), and 51Cr-EDTA clearance were measured. During the study 20 thorax-shielded and 19 thorax-irradiated animals died. All rats whose thoraxes received 25 Gy irradiation and three out of seven rats whose thoraxes received 20 Gy died 1 to 3 months postirradiation with massive pleural fluid accumulation. Shielding the thoraxes prevented this mode of death at these doses. Kidney injury was judged to be the primary cause of death of all thorax shielded animals and 15- and 20-Gy thorax-irradiated animals. Animals with kidney damage had elevated PUN and reduced 51Cr-EDTA clearance and hematocrits. The relative merits of each of these end points in assessing radiation-induced kidney injury after total-body exposure are discussed. PMID- 2108468 TI - Continuing unsafe sex: assessing the need for AIDS prevention counseling. AB - To assess the need for acquired immunodeficiency syndrome (AIDS) prevention counseling for gay and bisexual men who were continuing to engage in unsafe sex, a nonprobability telephone survey--the data may not be generalizable to the population--was conducted in Seattle during March 1987. In a 4-week period, 141 callers phoned in response to local publicity and completed a 30-minute anonymous interview. This paper focuses on 106 male respondents who were behaviorally defined as gay (that is, sex during the past year exclusively with partners of the same sex, N = 74) or bisexual (sex with both men and women, N = 32). The modal respondent was a never-married white male in his thirties who had some college education and was employed full-time in a white collar occupation. The gay men were more likely than the bisexual men to report that their family members and friends knew of their sexual orientation and to indicate that they were able to discuss their concerns about unsafe sex with someone close to them. Gay men were also more likely to use condoms and to have engaged in anonymous sex during the 3 months before the interview. More gay men had engaged in unprotected receptive anal intercourse (27 percent) than had bisexual men (13 percent), and in considerably more insertive anal intercourse (42 percent versus 22 percent). Of the gay men interviewed, 73 percent indicated that they needed help in changing their high-risk sexual behaviors compared with 61 percent of bisexuals. However, respondent preferences for the context of counseling (for example, sexual preference of the counselor,group versus individual counseling, type of agency) differed on the basis of the respondent's self definition of sexual preference. Bisexual men expressed a preference for individual therapy delivered by a private practitioner who is a heterosexual. The authors conclude that men who are at risk of AIDS due to ongoing unsafe sex will require a diversity of counseling options. PMID- 2108470 TI - [A mastocytoma of the liver--computed tomographic follow-up and biopsy]. AB - CT findings of a mastocytoma of the liver are reported. Follow-up studies over 1 year showed density changes in both the pre- and postcontrast scan. Diagnosis was established by percutaneous CT-guided biopsy, which was complicated by a simultaneous anaphylactoid reaction, probably due to direct histamine liberation. PMID- 2108471 TI - [Cellular signal transduction and protein mono(ADP-ribosyl)ation--regulation of signal transduction by endogenous mono(ADP-ribosyl)ation of GTP-binding protein]. PMID- 2108472 TI - Radiobiology of pions in comparison with other heavy particles. AB - Our recent data on late effects of pions in spinal cord, lung and rectum in rodents is presented with reference to other high-LET radiations. Unlike high-LET radiations such as neutrons and neon ions, the RBE for late effects of pions (up to 1.5) is not found to be significantly different from acute effects. Because of the potential of matching treatment volume (especially by using dynamic treatments) to the target volume by using pions and heavy ions, it is of utmost importance to study the tolerance of normal tissues to late effects as a function of volume. Such knowledge combined with pion and heavy ion dynamic treatment could lead to a further step in heavy particle radiotherapy. PMID- 2108473 TI - Proceedings of the international symposium of the EORTC-Heavy Particle Therapy Group. Villigen, Switzerland, 13-14 March 1987. PMID- 2108474 TI - Anaplastic astrocytoma and glioblastoma: pion irradiation with the dynamic conformation technique at the Swiss Institute for Nuclear Research (SIN). AB - Clinical phase I/II studies have been performed at the Swiss Institute for Nuclear Research (SIN) since February 1982. Fifty-two out of 249 patients accepted for pion treatment by the end of 1986 were treated for malignant glioma with high dose pion irradiation. A substantial influence of their radioresistance was expected from increased radiation quality due to the contribution of high LET particles from pion capture, and by the possibility of target volume shaping and dose distribution related to the dynamic spot-scan conformation technique. The patients' treatment followed a dose escalation program with total doses from 2720 3420 cGy, fraction sizes from 170 to 205 cGy (90% isodose, minimum target dose), and treatment times from 4 to 5 weeks. 12/52 patients received an accelerated treatment with 3280 cGy in 14-22 days. 49/52 patients are eligible: 3 with astrocytoma of clinical aggressive behaviour, 14 with anaplastic astrocytoma (median age 42 years), and 32 patients with glioblastoma (median age 52 years). 8/49 patients had total/subtotal tumour resection, 19 patients a stereotactic biopsy. The patients were divided into three groups according to total dose, and a fourth group which received the accelerated treatment. There was no statistically significant difference in the median survival rate between the four groups, which was 13 months for the non-glioblastoma patients and 9 months for the glioblastoma patients. No radiation necrosis and no demyelination was found in 17 patients (6 recraniotomies, 11 autopsies). In 10/17 patients, clearly identifiable tumour cells were not demonstrated. NMR findings showed the tumour surrounding oedema mostly stimulated by tumour necrosis and tumour progression. From these findings, further dose escalation programs, together with a shaping of the target volume close to the tumour, are not contraindicated. PMID- 2108475 TI - Review of the clinical results of fast neutron therapy. AB - The clinical results reported from the different neutron therapy centres are reviewed. Fast neutrons were shown to be useful in the treatment of locally extended inoperable salivary gland tumours (average local control rates 67% for neutrons compared to 28% for photons). For paranasal sinuses and some tumours of the head and neck area, especially extended tumours with large fixed lymph nodes, neutrons could also be of interest. By contrast, the results obtained for brain tumours were, in general, disappointing. Neutrons were shown to be beneficial in the treatment of well differentiated soft tissue sarcomas, as well as to bone- and chondrosarcomas. For locally extended prostatic adenocarcinoma, a RTOG randomized trial gave local control rates of 77% for mixed schedule compared to 31% for photons. Neutrons could be useful also for palliative treatment of melanomas. Further studies are needed in order to evaluate the benefit of fast neutrons for other localizations such as uterine cervix, bladder and rectum. It can be concluded that fast neutrons could be of interest for about 10% of the radiotherapy patients, but it is likely that the new high-energy hospital-based cyclotrons will further extend the indications of neutron therapy. However, patient selection remains one of the main problems and there is a need for development of individual predictive tests. PMID- 2108476 TI - A non-invasive method for fractionated stereotactic irradiation of brain tumors with linear accelerator. AB - A new technique for fractionated stereotactic irradiation of intracranial lesions is described. The treatment is based on a versatile, non-invasive interface for stereotactic localization of the brain target imaged by computed tomography (CT), angiography or magnetic resonance tomography (MRT), and subsequent repetitive stereotactic irradiation of the target using a linear accelerator. The fractionation of the stereotactic irradiation was intended to meet the requirements of the basic principles of radiobiology. The radiophysical evaluation using phantoms, and the clinical results in a small number of patients, demonstrated a good reproducibility between repeated positionings of the target in the isocenter of the accelerator, and a high degree of accuracy in the treatment of brain lesions. PMID- 2108477 TI - Expression of dose in neutron therapy. AB - A pragmatic approach in neutron dosimetry is to consider the energy spectrum to consist of a neutron and a gamma component. The relationship between the two components of dose in neutron radiotherapy has been investigated for energies currently in clinical use. Changes in the neutron component itself are not dealt with. Because the two components are given simultaneously there is some interaction between them so that the gamma fraction is more effective than if the neutron and gamma doses were separated in time. This interaction has been accounted for using a well-proven extension of the linear-quadratic (LQ) equation. Using values of the LQ parameters alpha and beta measured recently in vivo, we have modelled the total effect from the neutron and gamma dose contributions in terms of an equivalent neutron dose. This allows a comparison of different methods of expressing the measured physical dose with the biologically effective dose. The current practice in neutron therapy is to give the total (neutron plus gamma) dose, quoting also the gamma contamination. In all cases within the range of energies used for therapy, the total dose will give an overestimate of the biologically effective dose by approximately 4% for each 5% of gamma contamination. Expression of the neutron dose only (ignoring the gamma component) will give an underestimate of the biologically effective dose by approximately 1.5% for each 5% of gamma contamination, i.e. the error is approximately three times less for neutron dose than for total dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108478 TI - [Clinical use of pharmacologic monitoring at a hospital community]. AB - This study reveals the efficiency of phenobarbital, diphenilhidantoine, carbamazepine, valproic acid and teophyline serum levels for their correct adjustment within the concentration gap considered optimal to produce the desired pharmacological effect. A total population of 882 patients treated with the drugs previously named is studied and an important improvement in dose adjustment is observed during these years as a consequence of drug's serum level knowledge. PMID- 2108479 TI - [Secondary acute pancreatitis and diabetic ketoacidosis]. PMID- 2108480 TI - [Long-term outcome of surgically treated bullous emphysema]. AB - The long term outcome for 88 patients with bullous emphysema who had operations was analysed from the clinical, respiratory function and occupational point of view. In order to reduce to the minimum any bias which would be likely to appear as a result of a decrease in the number of patients with time respiratory function parameters were compared to those of a restricted number of patients for whom we knew all the values for each period determined. Before the operation all the patients showed radiological signs of bullous emphysema; the respiratory function measurements in 66 of them showed bronchial obstruction with distension, hypoxaemia at rest without hypercapnia. The clinical follow up and respiratory function was spread over more years. It showed a post operative improvement in dyspnoea which was perceptible in 77% of patients at 2 years, 68% at 3 years, 60% at 4 years, 51% at 5 years, 32% at 10 years. 2/3 of the patients who were working before the operation had taken up their normal work following it. the survival levels were 86% at 1 year, 83% at 2 years, 80% at 3 years, 78% at 4 years, 77% at 5 years, 73% at 6 years, 73% at 6 years, 58% at 10 years. Of 20 patients who died 12 had died of respiratory failure. All the spirographic parameters had improved following the operation but a secondary deterioration was noted around the 5th post operative year for the vital capacity, and at the third year for residual volume, FEV 1, and the FEV 1/VC ratio as well as PAO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108481 TI - [Electrophysiological effects of flecainide acetate on guinea-pig left atrial cells]. AB - Using conventional glass microelectrode technique, electrophysiological effects of flecainide acetate on guinea-pig left atrial muscle fibers were examined. Resting membrane potential was not affected by flecainide at any concentrations tested (10(-7) M-3 X 10(-5) M), although overshoot potential was significantly decreased at the concentration over 3 X 10(-6) M. Effective refractory period significantly increased at 10(-5) M. The reduction of Vmax was about 25% and 50% by 3 X 10(-6) M and 10(-5) M, respectively at 1 Hz. At 3 X 10(-6) M, Vmax decreased by about 10%, 15%, 22%, 33%, and 34% at 0.2, 0.5, 1, 2, and 3 Hz respectively. Flecainide, decreased Vmax of atrial muscle fibers in a dose and frequency dependent manner. It is suggested that flecainide might be effective in the treatment of atrial tachyarrhythmias. PMID- 2108482 TI - [Weightlessness and astronautics. Current trends in physiological research]. PMID- 2108483 TI - [Treatment of uterine fibroma using LH-RH analogs and gestrinone. Limits and indications]. AB - Medical treatment of fibroma has changed radically in recent years with the introduction of analogs of LH-RH (luteinizing hormone releasing hormone). These agents, which are active only via parenteral administration, have proved remarkably effective, and are devoid of metabolic effects. They do engender some disagreeable adverse reactions, and unfortunately their efficacy is transitory and their cost high. Compared with these analogs, gestrinone, a progestogen as yet unused in treatment of luteal insufficiency, seems very interesting in the treatment of fibromas, due to its prolonged antigonadotropic effect and its antiprogesterone effect. Further studies are required to confirm the first results published by Coutinho. PMID- 2108484 TI - [Nuclear magnetic resonance tomography follow-up in rapidly progressing central neurofibromatosis]. AB - The rapidly progressing deficits of a patient with known central neurofibromatosis (NF) led to a MRI control scan. Contrary to the previous non enhanced examinations we now saw multiple cerebral and spinal tumors, whose localisation and extension made surgical removal impossible. Gadolinium enhanced MRI is extremely useful in diagnosing and defining the extent of intracranial and intraspinal lesions, does not involve radiation exposure and should therefore be recommended generously in follow-up patients with known NF. This is the only feasible way to allow an early careful surgical removal of the tumors before reaching a point of no return. PMID- 2108485 TI - [Evaluation of intestinal permeability in ankylosing spondylarthritis with a test using Cr-EDTA]. PMID- 2108486 TI - Hepatobiliary compensation for the loss of gallbladder function after cholecystectomy. An experimental study in the cat. AB - The side effects of the removal of a functioning gallbladder are surprisingly few, and it has been suggested, but never demonstrated, that the hepatobiliary tract then adjusts to compensate for the loss of gallbladder function. In this study the effects of cholecystectomy on bile acid kinetics, bile flow, and biliary clearance of mannitol were studied in cats 6-8 weeks after cholecystectomy. An enhanced recycling rate of a diminished bile acid pool was found. The bile flow was reduced and the bile acid concentration in hepatic bile was increased, but fasting bile acid secretion rate was not changed. Both when the bile acid secretion rate was reduced by drainage via an acute bile fistula and when it was enhanced by intravenous infusion of glycocholic acid, there was a lower bile acid-independent flow in the cholecystectomy group. This reduced bile flow after cholecystectomy was not explained by the higher proportion of deoxycholic acid present in the bile of the cholecystectomized animals. Biliary clearance of mannitol, which is supposed to reflect the canalicular inflow, was not reduced, indicating that the reduction in bile flow is explained by a reduced fluid secretion or an enhanced fluid reabsorption in the bile ductules and ducts after cholecystectomy. In this manner the bile ducts compensate for the loss of the absorptive function of the gallbladder after cholecystectomy. PMID- 2108487 TI - Swainsonine, an inhibitor of glycoprotein processing, enhances cytotoxicity of large granular lymphocytes. AB - In the present study we investigated the effects of inhibitors of glycoprotein processing on cytotoxicity of human large granular lymphocytes (LGL). The incubation of LGL for 36 h with 0.5 microgram/ml swainsonine (SW), which is an inhibitor of mannosidase II, resulted in the augmentation of cytotoxicity of LGL against an NK-resistant colon carcinoma cell line (Colo-320DM) without increase of binding frequency of LGL to target cells or of cell proliferation. The enhanced cytotoxicity was associated with increased binding of concanavalin A to SW-treated LGL. The augmentation of cytotoxicity was also seen by 1 deoxymannojirimycin (1-DMN), an inhibitor of mannosidase I, but much higher amounts of this agent were needed to get the same level of augmentation as that with SW. Other inhibitors of glycoprotein processing such as castanospermine and 1-deoxynojirimycin (1-DN) did not show any augmentative effects on LGL cytotoxicity. The enhancement of cytotoxicity by SW was abolished by the addition of rabbit anti-human interleukin (IL-2) antibody to the culture. This result suggests that IL-2 is involved in the augmentation of cytotoxicity of LGL by SW. The presence of SW in the culture of LGL together with IL-2 also enhanced LAK generation compared to that with IL-2 alone. Thus, our results suggest that SW should be recognized as an efficient immunopotentiator and that modulation of carbohydrate moieties elicited by SW may shed further light on the mechanism of LGL activation. PMID- 2108488 TI - Lymphocyte subsets in the blood. The influence of splenectomy, splenic autotransplantation, ageing, and the site of blood sampling on the number of B, T, CD4+, and CD8+ lymphocytes in the rat. AB - Removal of the largest single lymphoid organ, the spleen, leads to an increase in severe infections. To prevent this, transplantation of splenic fragments can be performed, which may, however, cause an increase in CD8+ lymphocytes in the blood of these patients. This is controversial since in the clinical situation it is often difficult to account for the different age of the patients, the time point after the operation and many other factors known to influence the number of lymphocyte subsets. Using a well-defined animal model, B, T, CD4+, and CD8+ lymphocytes were determined preoperatively in adult rats. Then, either sham splenectomy, splenectomy, or splenic autotransplantation was performed and the animals were followed up for 15 months after the operation. The surgical procedure itself, the site of blood sampling and ageing all influenced the number of lymphocyte subsets profoundly. Furthermore, giving the data as relative or absolute numbers leads to different results. Splenectomy caused lymphocytosis, due to a significant increase in B and CD8+ lymphocytes, as did splenic autotransplantation, which indicates that the number of lymphocyte subsets in the blood should not be used to argue in favour of or against splenic autotransplantation. This study demonstrates that the number of lymphocyte subsets in the blood is influenced by many factors and therefore should be determined in a highly standardized fashion. PMID- 2108489 TI - Serum levels of the aminoterminal propeptide of type III procollagen and hyaluronan during resolving and nonresolving posttransfusion non-A, non-B hepatitis. AB - Serum levels of the aminoterminal propeptide of type III procollagen (PIIINP) and hyaluronan were analysed before and during the acute, recovery and chronic phases of non-A, non-B (NANB) posttransfusion hepatitis (PTH) in 13 patients. All patients were discovered during a prospective study on NANB PTH in patients undergoing open-heart surgery. 7/13 (54%) patients resolved their hepatitis within 6 months after onset, whereas 6/13 (46%) went on to chronic hepatitis. In 5 of these 6 patients a liver biopsy during the chronic phase of the hepatitis showed chronic active hepatitis in 2 and chronic persistent hepatitis in 3. During the acute NANB PTH phase the mean serum PIINP level rose significantly as compared to prehepatitis levels and to levels in a reference group not developing hepatitis. Neither PIIINP levels nor hyaluronan levels, however, could differentiate patients with resolving from patients with nonresolving hepatitis. These markers should, however, be further evaluated as potential markers for development of fibrosis/cirrhosis during chronic hepatitis. PMID- 2108490 TI - Long term androgen replacement therapy does not preclude gonadotrophin-induced improvement on spermatogenesis. AB - A previously hypophysectomized man with azoospermia, who was on androgen replacement therapy since 11 years, was studied with regard to his intratesticular steroid conversion capacity in vitro after which he was given combined hCG/hMG therapy. Before therapy a steroid conversion pattern similar to that seen in prepubertal boys was found, i.e. a high proportion of 20 alpha dihydroprogesterone was produced while only smaller amounts of 17 alpha hydroxyprogesterone was produced from the substrate 3H-progesterone. After only five weeks of hCG/hMG treatment, sperm counts and serum testosterone levels increased dramatically and a child was conceived. The steroid conversion pattern simultaneously switched to the mature, adult type with a low production of 20 alpha-dihydroprogesterone and large amounts of 17 alpha-hydroxyprogesterone being produced in vitro. Thus gonadotrophin substitution therapy may still be very effective after long term androgen replacement. PMID- 2108491 TI - Intravesical mitomycin C for carcinoma in situ of the urinary bladder. AB - Mitomycin C was given intravesically over periods of 2-32 months to 34 patients with carcinoma in situ of the urinary bladder. Initial complete response was obtained in 17 patients, 14 of whom remained without evidence of disease during follow-up averaging 28 months from cessation of mitomycin therapy. In three responding patients malignant cells reappeared in the urine during follow-up, although no recurrence of carcinoma could be proven in bladder biopsy specimens. In eight of the 17 non-responders, muscle invasion and/or metastatic disease developed during or after mitomycin treatment. The prostatic urethra was involved in five cases. Chemotherapy had to be discontinued because of chemical cystitis in three cases. Mitomycin C appears to be effective for intravesical treatment of carcinoma in situ of the urinary bladder. Close surveillance of these patients is mandatory, however, and must include monitoring not only of the bladder, but also of the prostatic urethra and the upper urinary tract. PMID- 2108492 TI - Serum hormone levels in men with end stage renal disease. AB - Serum concentrations of testicular and adrenal androgens and androgen precursors, cortisol, unconjugated (E1) and total estrone (tE1; greater than or equal to 85% E1 sulfate), pituitary hormones, sex hormone binding globulin (SHBG) and albumin were measured in 14 male patients with non-diabetic end stage renal disease and in 28 age-matched healthy controls. The serum levels of the adrenal androgens 4 androstene 3,17-dione and dehydroepiandrosterone (DHA) were significantly lower and the levels of cortisol, LH, prolactin and tE1 significantly higher in the patients than in the controls. The ratios between E1 and tE1 and between DHA and DHA sulfate were strongly decreased in the patients. The findings are suggested to reflect different effects of the disease upon the metabolism of cortisol and of adrenal androgens and also the reduced or even absent urinary excretion, leading to a decreased metabolism of steroid conjugates. PMID- 2108493 TI - [Neurogenic pulmonary edema complicating a generalized epileptic crisis]. AB - Epileptic seizures may be rapidly followed by neurologic pulmonary edema (NPE). While the outcome of respiratory failure may be spontaneously favourable, in some cases death may occur due to respiratory and/or neurologic dysfunction. Two patients with NPE are described, one of whom survived without treatment and is in good health. In the other the outcome was rapidly fatal despite prompt and vigorous medical treatment. PMID- 2108494 TI - Time trend of PCB concentrations in surface sediments from a hypertrophic, macroalgae populated area of the lagoon of Venice. AB - The concentrations of polychlorinated biphenyls have been determined over a period of 1 year in surface sediments sampled monthly and semi-monthly in the lagoon of Venice. At the sampling station, due to the poor water circulation and an over-abundance of nutrients, macroalgae thrive in spring-summer and standing crops greater than 12 kg m-2 were determined. As a consequence of rapid algal decomposition, sediment PCB concentrations were observed to increase. In particular, on occasions when anoxia occurred at the end of July and all the biomass had decayed, PCB concentrations increased by more than one order of magnitude. In March, when macroalgae started to grow, concentrations were 13 ng g 1 (dry wt); in July-August they exceeded 100 ng g-1. The sediment PCB concentrations were restored to the previous values after algal biomass became negligible, in November. Concentrations of PCBs in young algae fronds were 27 +/- 12 ng g-1, and 121 +/- 4 ng g-1 in older fronds. PMID- 2108495 TI - Geographical distribution of contaminants and productivity measures of herring gulls in the Great Lakes: Lake Erie and connecting channels 1978/79. AB - The distribution and size of colonies, residue levels of DDE, DDT, HCB, dieldrin, mirex and PCBs in eggs, productivity and eggshell thickness were determined for herring gulls at 14 sites in Lake Erie and connecting channels. The centre of distribution for breeding herring gulls was the Western Basin where approximately 90% of the 6200 nests in the study area were located. Seven of 22 colonies showed an average annual population increase of 48.3%. Most of the increase in breeding herring gulls on Lake Erie is directly associated with sites that have undergone habitat modification by man. Levels of PCBs and DDE ranged from 35 to 140 ppm (wet weight) and from 2.8 to 9.4 ppm, respectively; all other residues were less than 0.49 ppm. Most organochlorine residue levels were highest in eggs from colonies in or near the Niagara or Detroit Rivers. Mirex residues were greatest in the Niagara River and decreased significantly to the west. PCB residues were greatest in the Detroit River and decreased significantly to the east. The lowest levels generally came from colonies in the Sandusky Basin and near Pelee Island in western Lake Erie. Discriminant function analysis of six organochlorine contaminants correctly classified 90% or more of the eggs from up to four colonies in one or more years. Levels of PCBs and HCB appeared to have the greatest discriminating power. Herring gull productivity at all colonies (1-1.7 young gulls/pair) was normal and showed no significant geographical variation. Eggshell thickness was greatest in colonies in the Sandusky Basin and least in colonies in the Detroit River and extreme west end of the lake; mean eggshell thickness was 0.350 +/- 0.02 mm (6.7% thinning), which was weakly, but significantly correlated to DDE concentration. The variation in contaminants in herring gull eggs on a Basin basis (i.e., Western, Eastern, Sandusky, etc.) paralleled those known for sediments, water and fish. Thus, we suggest that in addition to its role as an indicator of lake-wide contamination of the Great Lakes, the herring gull, under some circumstances, may function as an indicator of "regional" contamination. This is an important distinction as it improves the geographical specificity of the herring gull as an indicator species on the Great Lakes, where it is a non-migratory species. PMID- 2108496 TI - Trials and tribulations of AIDS drug testing. PMID- 2108497 TI - Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. AB - EMT-6 murine mammary tumors were made resistant to cis-diamminedichloroplatinum (II) (CDDP), carboplatin, cyclophosphamide (CTX), or thiotepa in vivo by treatment of tumor-bearing animals with the drug during a 6-month period. In spite of high levels of in vivo resistance, no significant resistance was observed when the cells from these tumors were exposed to the drugs in vitro. The pharmacokinetics of CDDP and CTX were altered in animals bearing the respective resistant tumors. The resistance of all tumor lines except for the EMT-6/thiotepa decreased during 3 to 6 months in vivo passage in the absence of drugs. These results indicate that very high levels of resistance to anticancer drugs can develop through mechanisms that are expressed only in vivo. PMID- 2108498 TI - Isolation of a G protein that is modified by learning and reduces potassium currents in Hermissenda. AB - In Hermissenda crassicornis conditioned to associate light and rotation, type B photoreceptor neurons exhibit pairing-specific decreases in the potassium currents IA and IK-Ca, which account for many of the behavioral changes elicited by associative conditioning. To determine which proteins are involved in storage of this memory, high-performance liquid chromatography was used to examine proteins from Hermissenda eyes. Conditioning-specific changes in four phosphoproteins were observed 24 hours after conditioning. One of these proteins, cp20, was purified to apparent homogeneity and found to be a G protein. When injected back into Hermissenda type B cells, cp20 reduced IK and IK-Ca in a manner indistinguishable from the reduction caused by conditioning, suggesting that this protein may play a crucial role in memory acquisition or retention. PMID- 2108499 TI - Discovery of the oldest known anthropoidean skull from the paleogene of Egypt. AB - A group of primate fossils newly discovered in the Fayum badlands of Egypt is probably of Eocene age. The site is much older than the localities of previously known Egyptian early Tertiary primates. These finds include a crushed cranium that is the oldest skull found to date of a higher primate. This skull shows four characteristics of higher primates: a catarrhine dental formula, an ectotympanic at the rim of the auditory bulla, a fused frontal bone, and postorbital closure. Details of tooth structure (premolars and molars) and a possibly unfused mandibular symphysis resemble these parts in certain Eocene prosimians. PMID- 2108500 TI - Characterization of an extremely large, ligand-induced conformational change in plasminogen. AB - Native human plasminogen has a radius of gyration of 39 angstroms. Upon occupation of a weak lysine binding site, the radius of gyration increases to 56 angstroms, an extremely large ligand-induced conformational change. There are no intermediate conformational states between the closed and open form. The conformational chang is not accompanied by a change in secondary structure, hence the closed conformation is formed by interaction between domains that is abolished upon conversion to the open form. This reversible change in conformation, in which the shape of the protein changes from that best described by a prolate ellipsoid to a flexible structure best described by a Debye random coil, is physiologically relevant because a weak lysine binding site regulates the activation of plasminogen. PMID- 2108501 TI - Cost analysis of kinetic therapy in the prevention of complications of stroke. AB - We prospectively evaluated the costs of medical care in a group of 43 patients with acute severe stroke. Patients were assigned to either a routine hospital bed or a rotational bed. The rotational study bed (kinetic therapy) is designed to prevent complications of prolonged bed confinement by keeping patients in continuous slow rotation. The average number of acute care days was 11.2 in the study group and 16.4 in the control group. Study patients had similar costs per day for laboratory testing, x-ray studies, respiratory therapy, total acute care expenses, and total hospital expenses. Among study patients, reduction in medication costs per day did approach statistical significance, by unpaired t test, at P = .014, with a corrected significance level of .008. Overall, the average acute care costs per day were $544 in the study group verus $410 in the control group. This difference was approximately the average per day charge for the rotational bed ($130). We conclude that therapy designed to prevent complications of prolonged bed confinement is cost effective. PMID- 2108502 TI - Recurrent bacterial endocarditis in a man with tetralogy of Fallot: earliest recurrence on record. AB - Enterococcal endocarditis occurred in a young man with tetralogy of Fallot who had just completed therapy for staphylococcal endocarditis. The patient had a transient reversal of flow through the ventricular septal defect during staphylococcal endocarditis with lung abscesses and had persistently elevated teichoic acid antibody titers during the second episode caused by enterococcus. Our review of the literature on recurrent infective endocarditis indicates that our case represents one of the shortest intervals of recurrence with a second organism. PMID- 2108503 TI - Gentamicin-resistant enterococcal endocarditis: the need for routine screening for high-level resistance to aminoglycosides. AB - We have reported a case of high-level gentamicin-resistant enterococcal endocarditis as a complication of intravenous narcotic abuse. Because routine screening of enterococcal blood isolates for high-level aminoglycoside resistance was not done, the patient possibly received suboptimal therapy. This case amplifies the necessity of a systematic screening program for enterococcal blood isolates to detect high-level resistance to gentamicin and streptomycin in clinical laboratories. PMID- 2108504 TI - Long-term medical management of aldosterone-producing adenoma. AB - This case of Conn's syndrome demonstrates long-term (seven years) efficacy of triamterene-thiazide therapy in controlling both hypertension and hypokalemia. Studies done before the adrenal tumor was removed surgically showed that the tumor had increased in size and function since the first studies were done before triamterene-thiazide therapy. The resolution of hypertension after nine years of hyperaldosteronism suggests that surgery is effective even after chronic hyperaldosteronism has been present for some time. PMID- 2108505 TI - A dominant negative mutation in two proteins created by ectopic expression of an AU-rich 3' untranslated region. AB - We have found that the ectopic expression of a specific gene's 3' untranslated region leads to the dose dependent loss, relative to gene copy number, of that specific mRNA and protein, as well as an associated protein, in a eukaryotic cell line. The loss of these proteins from the eukaryotic cell line also results in specific phenotypic changes in these cells, suggesting that we have created a dominant negative mutant. This gene's 3' untranslated region is known to contain numerous AU sequences, reminiscent of other eukaryotic genes whose expression may be regulated by these sequences. The apparent control of gene expression by a truncated 3' untranslated region sequence provides further evidence supporting the regulatory function of these regions. The resulting decrease in steady-state mRNA levels by the overexpression of a portion of that gene's 3' untranslated region further suggests the possible existence of a factor(s) that may bind to this region, and thus regulate gene function via its mRNA. The use of a gene's 3' untranslated sequence to create a specific dominant negative mutation may also be applicable to other eukaryotic genes whose expression is controlled by similar regulatory sequences. PMID- 2108506 TI - Ventilatory responses to carbon dioxide in four ethnic groups in Cape Town. AB - Ventilatory responses to carbon dioxide (Sco2) were measured in 80 healthy adult subjects from four ethnic groups living in Cape Town. The mean Sco2 was 1.77 +/- 0.14 l/min/mmHg in whites, 1.13 +/- 0.09 l/min/mmHg in mixed race people, 0.99 +/ 0.11 l/min/mmHg in Indians and 0.87 +/- 0.10 l/min/mmHg in blacks. The difference between whites and the other three ethnic groups was highly significant (P less than 0.0001), whereas the differences between blacks, mixed race subjects and Indians were not. However, correction of Sco2 for differences in lung size, i.e. Sco2/vital capacity, eliminated the differences between whites and the other groups. PMID- 2108507 TI - The biologic characteristics of cytokines and their implication in surgical injury. AB - Cytokines are integral to normal homeostasis and to the response to injury. The biologic activities and synergistic actions of these proteins continue to be elucidated. In moderate quantities, these proteins likely confer such beneficial effects as myelostimulation, activation of immune cells and reprioritization of metabolic processes to provide substrates important in combating the results of injury. Exaggerated or prolonged production of these proteins, however, may produce detrimental effects that lead to a poor outcome. Specific antagonists against cytokines offer potential therapy in these instances of aberrant cytokine response. PMID- 2108508 TI - Intestinal permeability is increased in burn patients shortly after injury. AB - There is increasing direct experimental and indirect clinical evidence to indicate that under certain conditions intestinal barrier function may be lost in trauma victims. No direct measurements, however, have been performed in patients to determine whether intestinal permeability is increased shortly after a major thermal injury in the absence of infection. Fifteen hemodynamically stable burn patients with burns on more than 20% of their body surface (39% +/- 12%) had their intestinal permeability measured within 24 hours of injury with use of the two nonmetabolizable sugars lactulose and mannitol as permeability markers. Lactulose absorption was fourfold higher in the patients (223 +/- 54 mumol) than in the controls (58 +/- 11 mumole; p less than 0.02), whereas the lactulose/mannitol ratio was threefold higher (5.2 vs 1.7; p less than 0.05). Thus intestinal permeability was increased in patients with moderate to major burn injuries shortly after injury. PMID- 2108509 TI - Effect of lithium carbonate on mouse and rat embryos in vitro. AB - Lithium is effective in the treatment of manic-depressive psychosis but is suspected to be a developmental toxicant in humans. It is a developmental toxicant in mice and rats in vivo, but at human therapeutic serum levels of 0.6 1.6 meq/L, rats appear to be more sensitive to the effects of the drug than do mice. The species susceptibility to lithium-induced defects was evaluated by using a rodent whole embryo culture system employing mouse and rat embryos treated at comparable developmental stages. Mouse embryos were cultured on gestational days 8-10, and rat embryos were cultured on gestational days 10-12. Care was taken to insure that all embryos had 10 +/- 2 somite pairs at the beginning of the culture period. Embryos were cultured for 44 hours in rat serum to which lithium was added to attain final drug concentrations of 0.6, 1.2, 1.8, 2.4, or 5.0 meq/L. Control embryos were treated with distilled water, which served as the vehicle. In rats, lithium induced significant decreases in various parameters at 1.8, 2.4, and 5.0 meq/L; no malformations were observed in rats of this stage. In mice, significant decreases occurred at 2.4 and 5.0 meq/L, and embryos treated at the highest concentration had a significantly increased frequency of open neural tubes. Rat embryos were also cultured with lithium on gestational days 9-11. The lowest dose producing developmental toxicity at this stage was 0.6 meq/L. Open neural tubes were present among younger rat embryos; however, this defect occurred in all groups, including the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108510 TI - Almitrine bismesylate and oxygen therapy in hypoxic cor pulmonale. AB - The effect of oral treatment with the thiazine derivative almitrine bismesylate was studied in 28 patients with chronic obstructive pulmonary disease and arterial hypoxaemia receiving long term domiciliary oxygen therapy in a placebo controlled, double blind crossover trial. The initial treatment was given for three months and the second for two months. Because almitrine had an unexpectedly prolonged washout effect crossover analysis could not be performed; data from the placebo treatment administered in the second arm of the trial were used to calculate the half life of almitrine. Nine patients were withdrawn from the study (5 almitrine, 4 placebo). Patients' tolerance of the drug was good. The estimated plasma half life of almitrine was 20.5 days, considerably longer than previously reported. Almitrine caused a significant improvement in arterial oxygen tension (PaO2) with a mean maximum increase of 0.7 kPa at a plasma concentration of 500 ng/ml. Higher plasma concentrations were not associated with any further increase in PaO2. There was no significant effect on arterial carbon dioxide tension (PaCO2). In a second, acute study at the end of each arm of the chronic trial nine patients were subjected to increasing oxygen delivery rates (2, 4, and 6 l/min) for 90 minutes or until blood gas concentrations plateaued. Almitrine increased PaO2 in a dose dependent fashion at all delivery rates, but the effect diminished as PaO2 approached normoxic levels. There was no significant effect on PaCO2. Almitrine treatment results in a significant improvement in PaO2 over that achieved by oxygen alone, an effect that diminishes at high flow rates. Whether this is of clinical benefit is not known. In view of the prolonged half life revised dosage schedules are required. PMID- 2108511 TI - Effect of gamma aminobutyric acid on the carbon dioxide rebreathing response of normal subjects: a study using vigabatrin. AB - Animal studies suggest that gamma aminobutyric acid (GABA) may be an important neurotransmitter in the control of respiration. Vigabatrin, a new drug for the treatment of epilepsy, is thought to exert its effect by increasing GABA concentrations in the brain. To assess the effect of increased GABA concentrations in the brain on human respiration we measured the ventilatory response to carbon dioxide in seven normal subjects after they had taken vigabatrin or placebo for three days in a double blind crossover study. There was no change in either the slope or the intercept of the curve of the ventilatory response to carbon dioxide after vigabatrin by comparison with placebo. This study suggests that GABA does not have an important role in the control of respiration in normal individuals. PMID- 2108512 TI - [Blood transfusion in heart surgery]. AB - We have studied the effect of blood-saving measures in open heart surgery. Such measures were introduced in 1987. All fluids administered on the day of operation and on the first postoperative day were registered in all cardiac patients operated during one month in 1986, 1987, 1988. In 1986 the patients were exposed to a median of 21 donors while in 1988 they were exposed to a median of 2 donors. The reduction in transfusions was achieved by substituting plasma by polygeline, by giving thrombocytes only when there was a low thrombocyte count and by accepting a hemoglobin value of 9 g/100 ml before transfusion of erythrocytes. In 1988 most postoperatively drained blood was retransfused using a Sorensen retransfusion set. The reduction in transfusions has reduced the cost of each open heart operation by NOK 11,662. PMID- 2108513 TI - [Vena cava superior syndrome in total parenteral nutrition. Vena cava superior thrombosis caused by a central venous catheter]. AB - Two patients developed superior vena cava syndrome following total parenteral nutrition through a central venous catheter. Infection may have contributed to the development of the superior vena cava thromboses. In one patient a "sleeve thrombus" probably caused multiple pulmonary embolisms after the catheter was withdrawn. The other patient had a mural thrombosis with complete occlusion of the superior vena cava. The author emphasizes the importance of early diagnosis and correct treatment in order to reduce the high mortality rate due to this serious complication to central venous catheters. PMID- 2108515 TI - Correlation of serum interleukin-2 levels, soluble interleukin-2 receptors and T lymphocyte subsets in cancer patients. AB - An interleukin-2 (IL-2) in vitro reduced production has been observed in most metastatic cancer patients. At present, however, there are no data on blood IL-2 levels in vivo, because of the too low sensitivity of previous biological and enzyme immunoassay methods. The recent development of a sensitive RIA method allowed us to start a preliminary investigation of IL-2 production in basal conditions in human solid tumors. The study included 42 cancer patients. Breast and lung cancer were the two commonest neoplasms. Serum levels of IL-2 and soluble IL-2 receptors (SIL-2R), and CD4/CD8 ratio were measured in each patient. The control group consisted of 58 healthy subjects. Mean serum levels of IL-2 were significantly lower in metastatic patients (n = 23) than in those without metastases (n = 19). Patients with low CD4/CD8 ratio (n = 16) had significantly lower mean values of IL-2 than those with normal ratio (n = 26). Finally, mean IL 2 concentrations were significantly lower in patients with elevated levels of SIL 2R than in those with normal values. These results would suggest that metastatic dissemination is associated with a decreased IL-2 production in vivo, and that reduced IL-2 production is more frequent in patients with low CD4/CD8 ratio. PMID- 2108514 TI - Parasitic adaptations in the transmission of Theileria by ticks--a review. PMID- 2108516 TI - Open phase II with 5-fluorouracil, 4-epi-doxorubicin and mitomycin C (FEM) in advanced gastric cancer. AB - Forty-four patients with advanced gastric cancer were treated with a combination including 5-fluorouracil, 4-epi-doxorubicin and mitomycin C. 4-Epi-doxorubicin was substituted for adriamycin in MacDonald's original schedule. The combined treatment involved 600 mg/m2 i.v. of 5-fluorouracil on days 1, 8, 29 and 36; 80 mg/m2 i.v. of 4-epi-doxorubicin on days 1 and 29; and 10 g/m2 i.v. of mitomycin C on day 1. The cycle was repeated on day 57 after the start of treatment. Out of 44 patients, 39 were evaluable. Thirteen partial remissions (33%) were achieved. The average duration of remission was 7 months (range, 3-12 months). The average survival of the responders was 9 months, and that of nonresponders 3.5 months. Toxicity was moderate, well-tolerated and, as compared with the FAM schedule, less pronounced, particularly as regards myelotoxicity. Thus, the substitution of 4-epi-doxorubicin for adriamycin in the original schedule of MacDonald et al. (1980) did not improve treatment results, but the observed toxicity was less pronounced. PMID- 2108517 TI - Long-term results with the Gn-RH analogue, buserelin, in metastatic prostate cancer. AB - LH-RH analogues have come into use to suppress the synthesis of testosterone by the testes and to induce palliation in advanced prostate cancer. Twenty-one patients were treated with buserelin (Hoe 766), and 19 were evaluable. Stages of disease were D1-D2. Seventeen patients responded to treatment, 3 patients are still in partial response, and 16 underwent progression. The median time to progression was 12 months (range, 3-36), and the median follow-up time was 10 months (mean, 25.4; range, 5-48). PMID- 2108518 TI - Behavioral effects of increased CO2 load in divers. AB - The behavioral effects of elevated PACO2 were examined to clarify risks due to CO2 retention in diving. In two separate laboratory studies, experienced divers breathed 6% CO2 mixtures under normobaric conditions. Normoxic study: Subjects (n = 8) first breathed air (control); then 6% CO2, 21% O2, balance N2 (exposure); and then air again (postexposure). Hyperoxic study: Subjects (n = 10) first breathed 100% O2; then 6% CO2 in O2; and then O2 again. Subjects performed a test battery in each condition. In the control and postexposure conditions, tests consisted of simple and choice reaction time, postural sway, tremor, and hand steadiness. In the exposure conditions, only the simple and choice reaction time tests were performed. No significant performance decrements during CO2 exposure were found in either study. However, regression analyses indicated that changes in postural sway, tremor, and decision-making time after normoxic CO2 exposure were proportional to decrements in individual end-tidal PCO2 levels following CO2 exposure. We conclude that divers may be at risk for performance impairment immediately after a period of CO2 retention. PMID- 2108519 TI - Neuropathic bladder in ankylosing spondylitis with spinal diverticula. AB - Cauda equina type of syndrome with neuropathic bladder is a rare but known complication of long-standing ankylosing spondylitis. From 1968 until now, diverticula from the subarachnoid space eroding into the bodies of the lumbosacral vertebrae have been reported in 46 cases of ankylosing spondylitis with cauda equina syndrome and neuropathic bladder. We report 3 cases of neuropathic bladder and ankylosing spondylitis with cauda equina symptoms. In 1 of the 3 patients, these rarely encountered spinal diverticula were demonstrated by computerized tomography (CT) scan. The etiology of these diverticula and their treatment are reviewed. PMID- 2108520 TI - Human os penis. AB - We report a case of human penile ossification with roentgenologic and histologic confirmation. The English literature is reviewed, and the pathogenesis of such a rare lesion is presented. Penile ossification appears to be an acquired metaplastic process occurring in an area of fibrosis. PMID- 2108521 TI - [OKT 3 treatment of kidney transplant recipients]. AB - Anti-rejection therapy with the monoclonal antibody OKT 3 was effective in the treatment of acute rejection episodes in 66% (47/71) of OKT 3 treated kidney graft recipients. The success of OKT 3 therapy, however, appeared to be dependent on certain variables. Reversal of rejection differed significantly according to the indication, namely if patients were treated first line, as opposed to rescue therapy. Vascular components of rejection and/or severe interstitial rejection, as well as acute tubular necrosis were associated with a worse reversal rate. Non responders to OKT 3 presented with significantly lower serum OKT 3 trough levels during the first three days of the treatment course. The presence of more than one of these risk factors was shown to decrease the reversal rate of rejection significantly. The variables appeared to exert their influence in an additive fashion. Administration of OKT 3 led to the induction of an acute phase reaction, which could be detected within one day after start of therapy. The incidence of both bacterial and viral infection was increased dramatically in OKT 3 treated patients as compared with graft recipients who were not treated with monoclonal or polyclonal antilymphocyte antibodies. The findings demonstrate that OKT 3 is of value in the treatment of acute rejection episodes but provide evidence of differential indications for OKT 3 therapy, which must be taken into account to optimize control of rejection and avoid unnecessary side effects where the drug is not indicated. PMID- 2108522 TI - [Craniocervical amyloid tumor with destructive spondyloarthropathy and myelocompression as a rare complication of long-term dialysis]. AB - Dialysis-associated amyloidosis has become a frequent and sometimes disabling complication in long-term dialysis patients. The main protein implicated in amyloidosis is beta 2 microglobulin, which accumulates in patients with renal insufficiency. We report on a 47-year-old patient, who was on haemodialysis treatment for 17 years. After a period of 15 years on dialysis treatment he underwent surgery for a carpal tunnel syndrome. Two years later he developed destructive spondyloarthropathy of the cervical region and destruction of the occipital bone. He lost stability of his neck necessitating his remaining mainly in the lying position. Since the type of dialysis membrane may play an important role in the pathogenesis of dialysis-associated amyloidosis, a dialysator with a polysulfone membrane, which is assume to have a beneficial effect on the progression of amyloidosis, was established. PMID- 2108523 TI - Evaluation of certain food additives and contaminants. Thirty-fifth report of the Joint FAO/WHO Expert Committee on Food Additives. PMID- 2108524 TI - Preoperative localization in unilateral parathyroid surgery. A cost-benefit study on ultrasound, computed tomography and scintigraphy. AB - In 50 patients with primary hyperparathyroidism, investigation before initial neck exploration included ultrasonography, computed tomography and 99technetium 201thallium subtraction scintigraphy. The sensitivity for correct preoperative localization was 50%, 54% and 56%, respectively. There was marked inter-observer variation in assessment of ultrasonography and computed tomography, while scintigrams were evaluated by only one person. The scintigraphic sensitivity increased with size of the glands. In cases where correct preoperative localization permitted unilateral parathyroidectomy, the time for surgery and anesthesia was significantly reduced. A cost-benefit analysis, however, revealed that the financial saving from this time reduction was outweighed by the cost of the localization procedures. The authors conclude that investigations for definition of enlarged parathyroid glands are not indicated prior to unilateral parathyroidectomy. PMID- 2108525 TI - Inflammatory epithelial changes and nonviral cervicovaginal pathogens. AB - To assess the relationship between inflammatory epithelial changes (IECs) and cervicovaginal infection, 249 women with cytologic diagnoses of IEC were studied. The findings showed a Chlamydia infection in 15.7% of the cases, Monilia in 38.1%, Trichomonas in 1.6% and a lateral vaginal wall pH of greater than 5.5 in 29.7%. These results were compared with those for 211 controls drawn from the same population; women with abnormal cytologic reports were excluded from the control group. The controls had a prevalence of yeast and trichomoniasis no different from that of the IEC group. In contrast, the prevalence of chlamydial infection (7.6%) and pH greater than 5.5 (10.7%) were significantly lower in the controls than in the IEC cases. Chlamydia was found in 30.2% of 43 women with an atypical transformation zone, equally distributed between women whose biopsies were normal and those whose biopsies showed cervical intraepithelial neoplasia. The traditional guidelines of treating cases with cytologic diagnoses of IEC prior to obtaining a repeat smear may need reevaluation in the light of these findings. PMID- 2108526 TI - Masson's vegetant intravascular hemangioendothelioma. Fine needle aspiration cytology, histology and immunohistochemistry of a case. AB - Masson's vegetant hemangioendothelioma is a benign intravascular tumor, sometimes confused with such malignant vascular tumors as angiosarcoma, whose clinical appearance is nonspecific and whose diagnosis can only be established through microscopic examination. The fine needle aspiration (FNA) cytologic findings together with the histologic and immunohistochemical findings of such a tumor in a 22-year-old man are presented. Cytologically, the material obtained by FNA consisted of two distinct populations of cells. One type of cell had large nuclei (sometimes displaced towards the periphery), finely granular chromatin, prominent nucleoli and abundant globular cytoplasm. The second type of cell had spindle shaped or oval nuclei, granular chromatin and scanty eosinophilic cytoplasm. Although these findings may permit the cytologic recognition of this entity, the aspirate in this case was interpreted as showing a vascular mesenchymal tumor of probable malignancy. Histologic examination of the excised tumor, aided by immunoperoxidase studies for factor VIII antigen that revealed the endothelial nature of the proliferating cells, established the correct diagnosis. PMID- 2108527 TI - Effect of an intravenous gammaglobulin preparation on the opsonophagocytic activity of preterm serum against coagulase-negative staphylococci. AB - Recent reports have described cases of septicaemia caused by coagulase-negative staphylococci in preterm neonates, mainly due to the use of artificial intravenous devices. It was of interest to examine if intravenous immunoglobulin therapy, known to be effective in group B streptococcal infections of neonates, had a similar beneficial effect in coagulase-negative staphylococcal infections. Opsonophagocytosis of coagulase-negative staphylococci by normal polymorphonuclear leukocytes in the presence of cord blood serum supplemented with the commercial IgG preparation 'Sandoglobulin' was investigated, using luminol-dependent chemiluminescence. It was found that with two different coagulase-negative staphylococcal strains, Sandoglobulin had a concentration dependent enhancing effect on the chemiluminescent response. This effect was demonstrated in the presence of native as well as inactivated cord blood serum and in the presence of sera from preterm infants (28-33 weeks). It is concluded that intravenous Sandoglobulin therapy may be effective in the treatment of preterm infants with severe coagulase-negative staphylococcal infections. PMID- 2108528 TI - Minimal enteral feeding, nasojejunal feeding and gastrin levels in premature infants. PMID- 2108529 TI - Self-induced pattern-sensitive epilepsy in childhood. AB - We studied five children (1 boy and 4 girls) with self-induced pattern-sensitive epilepsy. All patients had refractory epilepsy with multiform, though mainly myoclonic, seizures and medium grade to severe mental retardation. Spontaneously self-induced seizures were documented in all cases by EEG. All the patients underwent full neurophysiological assessment (baseline EEG recording, with activation: eyelid closed, hyperventilation, ILS, EEG during the randomized presentation of 3 types of spatial structured stimuli, VEP-F and VEP-PR). The pattern that triggered the EEG anomalies was highly specific and selective for each patient. Clinical seizures were reproduced by the same patterns as the ones used by the patients to bring on the seizures at will. Authors stress the importance of identifying such peculiar type of epilepsy and of attempting adequate treatment. PMID- 2108530 TI - Possible roles for zinc in destruction of Trypanosoma cruzi by toxic oxygen metabolites produced by mononuclear phagocytes. AB - The effects of a single nutrient deficiency on immune function is now most extensively characterized using the dietary zinc deficient murine model. Deficiencies in zinc have rapid adverse effects on host defenses of humans and rodents. This impaired defense seems to be, in part, the result of a reduction in number of lymphocytes available for surveillance since residual lymphocytes are able to carry out many normal functions. In vitro, the lymphocytes were able to proliferate at a normal rate as well as produce antibodies or interleukin 2 in response to mitogens or antigens even when cultured in autologous serum to reduce the possibility of restoration of zinc deficient functions. Conversely, mononuclear phagocytes (MNP) from deficient mice had a significantly reduced capacity to associate with and kill the parasite Trypanosoma cruzi (T. cruzi) which causes Chaga's disease. Moreover, indicating the specificity of the deficient function, a short incubation of ZnCl2 but not other metals completely restored the capacity of MNP from deficient mice to take up and kill T. cruzi. Dependency on H2O2 production by the MNP's oxygen burst for killing of T. cruzi.suggested that MNP from zinc deficient mice might produce smaller amounts of H2O2. The possibility that zinc might play an integral role in the oxygen burst seemed evident from the ability of zinc to quickly restore the killing capacity of MNP from the zinc deficient mice. Further, the renewed interest in the role of metals in the production of highly reactive oxidants in biological systems prompted a literature search to identify enzymes and/or reactions known to be involved in the generation of oxygen radicals or toxic oxygen metabolites that might be zinc dependent. The literature review provided herein indicates many possible roles for zinc in the generation of toxic oxygen species. The data indicated that normal levels of H2O2 are produced by MNP from zinc deficient mice. The amount of H2O2/mg macrophage protein is normal in response to phorbol or opsonized zymosan but reduced in response to direct stimulation by T. cruzi. However, the reduced H2O2 production by T. cruzi-stimulated zinc deficient MNP was due to reduced stimulation as a result of fewer T. cruzi associated with the MNP. Thus, H2O2 levels/parasite were the same as zinc adequate controls. Yet, this does not preclude the possibility that reduced killing of T. cruzi by MNP from zinc deficient mice may be due to a function for zinc in the actual killing process or in the production of some other agent important in the killing of T. cruzi. PMID- 2108531 TI - Cellular and molecular basis of nutrition-immunity interactions. PMID- 2108532 TI - The administration of beta carotene to prevent and regress oral carcinoma in the hamster cheek pouch and the associated enhancement of the immune response. AB - In the past four years this laboratory has utilized the hamster cheek pouch tumor model to investigate the anticancer activities of antioxidants, such as beta carotene. These molecules, which have exhibited no evidence of toxicity, have been administered systemically (oral ingestion), and locally to the tumor site in the hamster cheek pouch. The results have been either the inhibition of tumor growth, or the regression of tumor. Adjacent to the degenerating tumors a dense inflammatory infiltrate was observed. Specifically, the cytokines, tumor necrosis factor alpha, and beta, have been immunohistochemically localized to the site of regressed oral carcinoma. Recently, liposomes composed of phosphaditylcholine, phosphaditylserine, and phosphodityelanolamine were combined with beta carotene and injected locally to oral squamous cell carcinoma of the hamster. The results indicated that tumor cells accumulated the liposomes and were lysed while normal mucosal cells did not demonstrate this effect. Therefore antioxidants such as beta carotene can be localized to a tumor site, without a toxic response. Future studies on the anticancer activity of the antioxidants need to focus on the cellular and molecular changes produced in the immune effectors and in the mucosal cells following administration of the antioxidants. PMID- 2108533 TI - Percutaneous gastrostomy with gastropexy: experience in 125 patients. AB - We report our experience with radiologically guided percutaneous tube gastrostomy in 125 patients by using a gastropexy technique in which the anterior gastric wall is nonsurgically sutured to the anterior abdominal wall with percutaneously placed T-fasteners before catheter insertion. Short-term follow-up of up to 2 weeks was available in all patients. In 63 patients, long-term follow-up (greater than 4 weeks; average, 3.5 months; maximum, 1 year) was available. Catheter placement was successful in 124 (99%) of 125 patients, including three patients with anatomic changes after Bilroth II hemigastrectomy and two patients with failed endoscopic attempts. There were no deaths related to the procedure, and no patients required surgical intervention for complications attributable to the gastrostomy procedure. The 30-day mortality rate was 11% (n = 7). These deaths were due to cardiorespiratory arrest and were not attributable to the gastrostomy procedure. Major complications occurred in 1.6% (n = 1) and minor complications in 9.5% (n = 6). These results indicate that percutaneous gastrostomy with gastropexy is a safe and effective technique for placement of catheters in the stomach. PMID- 2108534 TI - CT of the abdomen after the Whipple procedure: value in depicting postoperative anatomy, surgical complications, and tumor recurrence. AB - We performed a retrospective study of CT scans in 29 patients who had undergone the Whipple procedure (radical pancreaticoduodenectomy) to study the CT appearance of the postsurgical anatomy and assess the use of CT in the evaluation of early postoperative complications and recurrent tumor. In the postoperative period, the scans from 15 patients revealed seven transient fluid collections; four deep abscesses, three of which were successfully drained under CT guidance; three superficial abscesses; and five cases of ascites. In 19 patients, CT scans were obtained up to 4 years after surgery to search for recurrent tumor. The most frequent site of recurrence was the liver. CT correctly identified liver metastases in six of seven patients and was falsely positive in one. Recurrence also was found twice in retroperitoneal lymph nodes; one time each in the mesenteric root, spleen, and lung base; and twice causing afferent loop blockage. Surgical proof of recurrence was obtained in eight cases. Our experience suggests that an understanding of the normal postoperative anatomy following the Whipple procedure is essential in evaluating postoperative CT scans. Scans obtained for detection of tumor recurrence should be optimized for imaging the liver because this was the most frequent site of recurrence. PMID- 2108535 TI - Hepatic subcapsular hematoma: an unusual complication of biliary lithotripsy. PMID- 2108536 TI - Adult ankle fractures: comparison of plain films and interactive two- and three dimensional CT scans. AB - Thirteen patients with 15 ankle fractures potentially requiring surgical reduction according to plain film criteria were studied with transaxial CT, from which static and animated interactive two-dimensional (2-D) images and animated volumetric three-dimensional (3-D) images were generated. CT criteria believed to parallel well-accepted plain film criteria for triage of ankle fractures were developed and applied. The tibiofibular, talofibular, and tibiotalar articulations were characterized and, where possible (nine cases), compared with the (presumably normal) contralateral ankle. Talocrural angle measurements were made on interactive coronal measurements and compared with standard plain film measurements. Fracture fragment displacement, rotation, and impaction were noted. Posterior tibial lip disruption was quantified. Information derived from the 2 D/3-D CT study led to cancellation of proposed surgery in three of the distal fibular fractures and in two distal tibial fractures. There was far less variation than anticipated between the talocrural angles of the injured and normal ankles, and both injured and normal ankles deviated significantly from the accepted standard of 84 degrees. Displacement at the level of the fibular fracture was a poor predictor of more distal disruption. Two-dimensional CT was found to provide anatomic detail and information superior to either plain film or 3-D CT; 3-D CT was preferred by the surgeons for final surgical planning and for integration of the 2-D data. CT altered management in five of the 13 patients studied, supporting our belief that 2-D/3-D CT can be of significant value in assessing ankle fractures. PMID- 2108537 TI - Insufficiency fracture of the sternum caused by osteopenia: plain film findings in seven patients. AB - Sternal insufficiency fractures, whether nonbuckling (displaced or nondisplaced) or buckling, are rare and have been described in elderly osteopenic patients with accentuated kyphosis of the thoracic spine. We retrospectively analyzed the radiographs and clinical records in seven osteopenic patients with sternal insufficiency fractures and correlated the type of insufficiency fracture with the presence and degree of dorsal kyphosis, as well as the presence of chest pain, soft-tissue mass, and osteolysis. We found that displaced or nondisplaced nonbuckling fractures (five patients) may be associated with chest pain localized to the sternum (three patients), and may be present with (three patients) or without (two patients) associated thoracic kyphosis. This type of insufficiency fracture also may be accompanied by a soft-tissue mass and osteolysis (three patients), findings simulating pathologic fractures. All buckling insufficiency fractures (two patients) were associated with thoracic kyphosis and were asymptomatic. Our findings suggest that sternal insufficiency fractures may occur with or without exaggerated dorsal kyphosis. The fractures are an uncommon complication of osteopenia and may resemble pathologic fractures when osteolysis and soft-tissue swelling are present. PMID- 2108538 TI - The Neer classification of displaced proximal humeral fractures: spectrum of findings on plain radiographs and CT scans. PMID- 2108539 TI - Differentiation of child abuse from osteogenesis imperfecta. PMID- 2108540 TI - Differentiation of child abuse and osteogenesis imperfecta: medical and legal implications. PMID- 2108541 TI - Castleman disease in the neck: atypical appearance on CT. PMID- 2108542 TI - The role of ferritin and hemosiderin in the MR appearance of cerebral hemorrhage: a histopathologic biochemical study in rats. AB - A rat model of cerebral hemorrhage using stereotaxic injection of blood into the right basal ganglia was developed to investigate the influence of iron metabolism on the appearance of cerebral hemorrhage on MR images. Images of in vitro fixed brain sections stained specifically for different iron-storage substances, ferritin and hemosiderin, created by digitization of the pathology sections using an Eikonix CCD camera, were compared with the in vivo MR images of late-phase hematomas. Areas of the pathologic and MR features of the lesions were quantitatively correlated. The single-slice MR images were obtained with the use of T1- and T2-weighted spin-echo pulse sequences, as well as T2-weighted spin echo pulse sequences in which the 180 degrees refocusing pulse was offset from the center of the echo time; this was termed an asymmetric spin-echo pulse sequence. The symmetric and asymmetric T2-weighted images allowed the calculation of line-width images, which emphasize line broadening from intravoxel magnetic field inhomogeneities that arise from the presence of iron-containing substances. From biochemical and histochemical staining, we conclude that at least two iron storage substances are present in the late phase of resolving cerebral hematomas. Ferritin has a wider distribution than hemosiderin, showing a similar distribution to the MR signal changes of the calculated line-width images. Line width mapping is a sensitive means of detecting magnetic field inhomogeneities caused by the magnetic susceptibility differences introduced by the aggregation of these iron-storage substances. PMID- 2108543 TI - Carotid artery disease assessed by color Doppler flow imaging: correlation with standard Doppler sonography and angiography. AB - Carotid artery disease was assessed in 180 patients by means of color Doppler flow imaging. Color Doppler findings in 360 carotid arteries were compared with the results of standard Doppler sonography, and color Doppler findings in 60 bifurcations were compared with the results of intraarterial angiography. The sensitivity of color Doppler for the detection of carotid disease was 100% when compared with angiography. The accuracy of color Doppler in classifying minor (40 60%), moderate (61-80%), and severe (81-90%) stenosis ranged from 91.3% to 97.8% vs standard Doppler sonography, and from 91.7% to 95.8% vs angiography. Whereas all occlusions were identified correctly by both color Doppler and angiography, four pseudoocclusions of the carotid artery were misdiagnosed as occluded. Characteristic features providing reliable criteria of the degree of stenosis are (1) intensity, extent, and duration of color fading; (2) postprocessed systolic peak frequency; (3) plaque extent on serial sonograms; and (4) poststenotic flow patterns. Display of hemodynamic disturbances induced by less pronounced plaques showed highly variable patterns that could not be anticipated from the plaque morphology alone. Thus, color Doppler preserves the advantages of standard Doppler and duplex sonography but provides additional information about otherwise anechoic necrotic and thrombotic material that often causes cerebral embolisms. With atherogenesis, repair mechanisms may be sustained or progression be stopped by reducing the risk factors and instituting medical treatment; thus, the application of this noninvasive technique is important. PMID- 2108544 TI - Pseudoatrophy of the cervical portion of the spinal cord on MR images: a manifestation of the truncation artifact? AB - Routine evaluation of axial MR images of the cervical spine with high-intensity CSF (long TR/TE spin-echo or gradient-echo images) revealed apparent narrowing of the cord's anteroposterior diameter when these images were compared with corresponding postmyelography CT scans. This discrepancy was believed to be due to the truncation artifact at the CSF-cord boundary. To examine the truncation effect, we compared cord diameters in 12 patients on postmyelography CT scans and MR images and then compared these with MR scans of normal volunteers and of an agar-saline spine phantom. There was an artifactual diminution of the cord diameter in the 128-step phase-encoding axis of the 128 x 256-matrix MR scan as compared with the diameter of the cord in the patients' postiohexol CT scans and in the 256 phase-encoded axis MR scan in the volunteer study. A similar discrepancy was noted in the spine phantom study, in which the cord diameter in the 256-step phase-encoded MR scan, the CT scan, and direct measurement exceeded that in the 128-step phase-encoded axis MR scan. The range of differences between the measurements was as large as 2.3 mm (patients), 1.7 mm (volunteers), and 1.8 mm (phantom) for the three studies. In all three studies, varying the photographic window width and level produced variation in the apparent cord diameter of up to 1.5 mm. To eliminate this effect, the cord diameters in the phantom and the normal control subjects were measured at identical window levels. The truncation artifact, coupled with standard window settings used in photography, may lead to inaccurate display of the diameter of the cervical spinal cord. PMID- 2108545 TI - The diagnosis of acromegaly: value of inferior petrosal sinus sampling. AB - The early diagnosis of acromegaly may be difficult when serum levels of growth hormone are minimally elevated and imaging of the pituitary gland fails to show an adenoma. However, transsphenoidal surgery has the greatest chance of cure at this stage. We therefore investigated the value of sampling petrosal sinuses for measurement of growth hormone in this group of patients. Simultaneous bilateral sampling of the inferior petrosal sinuses to measure serum concentrations of growth hormone was performed in five patients suspected of having acromegaly but with nondiagnostic CT scans (n = 5) and MR images (n = 3) of the pituitary gland. Levels of growth hormone from the petrosal sinuses were five to 36 times greater than levels in the peripheral veins in all five patients, and three of four showed a marked response to growth hormone-releasing hormone. During transsphenoidal surgery, growth hormone-producing microadenomas were resected completely in four patients. In the fifth patient, a left-sided microadenoma had invaded the cavernous sinus and could not be resected completely. Lateralization of the adenomas within the pituitary gland on the basis of differences in levels of growth hormone between the two petrosal sinuses was not completely reliable. Elevated levels of growth hormone in selective samples from the inferior petrosal sinuses can help support an early diagnosis of acromegaly when peripheral growth hormone levels and imaging are not diagnostic. PMID- 2108546 TI - CT evaluation of anaplastic thyroid carcinoma. AB - CT findings in 19 patients with anaplastic thyroid carcinoma were compared retrospectively with pathologic findings and the results of palpation. The carcinoma appeared as a large mass of low attenuation accompanied by dense calcification in 58% of the patients; there was necrosis in 74%. Often, adjacent structures were infiltrated. CT correctly showed tumor invasion of the carotid artery (7/7), internal jugular vein (9/10), larynx (5/6), trachea (8/10), esophagus (4/5), mediastinum (5/5), and regional lymph nodes (14/16). Seven patients (50%) had necrotic nodes. CT was superior to palpation in the detection of a primary tumor in one patient and of metastatic nodes in seven patients. It suggested a suitable place for biopsy in two patients, leading to a correct diagnosis. CT altered surgical planning in five patients with intrathoracic extension of the thyroid tumor, and in three patients with laryngeal or esophageal invasion of the tumor. CT can increase diagnostic accuracy in patients with anaplastic thyroid carcinoma by suggesting a likely diagnosis and by indicating an appropriate site for biopsy. It is indispensable in the planning of surgery for patients with this disorder. PMID- 2108547 TI - Nonsurgical treatment of primary hyperparathyroidism with sonographically guided percutaneous injection of ethanol: results in a selected series of patients. AB - Twelve patients with primary hyperparathyroidism were treated with sonographically guided percutaneous injection of ethanol (96%) into solitary parathyroid tumors verified by biopsy. The patients were all selected for nonoperative chemical parathyroid ablation either because of acute severe hypercalcemic symptoms (four patients), a high surgical risk or an advanced age (four patients), or refusal of a surgical intervention (four patients). Before treatment, the serum concentration of ionized calcium ranged from 1.38 to 2.39 mmol/l (median, 1.59 mmol/l), and after the last treatment the serum concentration ranged from 0.80 to 1.47 mmol/l (median, 1.32 mmol/l) (p less than .001). Normocalcemia was achieved in eight patients, and evident clinical improvement was seen in seven patients. The only complication was a permanent unilateral vocal cord paralysis due to involvement of the recurrent laryngeal nerve. The present study confirms the possibility of percutaneous treatment of hyperactive parathyroid glands. However, the treatment was not found to be beneficial to all patients and hypercalcemia recurred. On the basis of our experience with these patients, we conclude that sonographically guided chemical parathyroidectomy should be considered an alternative treatment to surgery in patients who are not suited for surgical intervention. PMID- 2108548 TI - A solution to the problem of high-flow jets from miniature angiographic catheters. AB - In this study we evaluated methods for reducing high-flow jets from 5-French catheters that occur when injection pressures approach catheter tolerance (1000 psi [6.9 MPa]). This "jet effect" has been responsible for subintimal extravasation of contrast material in patients. We designed a physical model that accurately measures flow rates through the end hole and each side hole of 5 French high-flow catheters under simulated physiologic arterial pressure. When a standard catheter commonly used for injection of contrast material was studied, flow of contrast material was 34% through the end hole and 31% through the distal side-hole pair at high injection pressures (1000 psi). We examined the effect of altering the size and configuration of catheter side holes and end hole in an effort to create an improved flow profile, and thus a safer angiographic catheter. End-hole flow rate was reduced by 73% to 9% of total flow by tapering the 5-French catheter to 0.018 in. (0.046 cm) and by using smaller 0.015-in. (0.038-cm) side holes for even flow distribution. The high-flow jets present with standard high-flow 5-French catheters do not occur when flow-restrictive end holes and side holes are used. A uniform flow profile can be obtained without sacrificing delivery of contrast material through small catheters. PMID- 2108549 TI - Transcatheter thrombosis of a leaking saccular aneurysm of the main renal artery with preservation of renal blood flow. AB - Percutaneous techniques have been used in the treatment of aneurysms and pseudoaneurysms in a variety of anatomic locations, including the kidney. An elderly patient with a leaking saccular aneurysm of the main left renal artery was considered a poor operative risk. We were able to embolize and thrombose the aneurysm selectively by using a combination of coil springs, guidewire, thrombin, and bucrylate without occluding the renal artery. PMID- 2108550 TI - Use of the Hawkins-Hunter rocket wire in the biliary system. PMID- 2108551 TI - Complications from 0.018-in. floppy platinum-tip guidewires. PMID- 2108552 TI - Phlegmasia cerulea dolens, a complication after placement of a bird's nest vena cava filter. PMID- 2108553 TI - Evaluation of radiographs developed by a new ultrarapid film processing system. AB - The image quality of radiographs developed by a new ultrarapid processor was evaluated to determine if faster processing causes degradation in the image. The processor used was the Konica Super-Rapid SRX-501 model. Two films designed for this processor (Konica MGH-SR and MGL-SR) were processed in 45 sec and were compared with standard rapid processing in 90 sec of corresponding conventional films (Kodak TMG and OC). Rare-earth screens (Kodak Lanex Regular and Lanex Medium) used with the new and conventional films interleaved during angiographic studies or for phantom images were assessed for image quality. The basic imaging properties of the screen-film systems were examined by measuring (1) Hurter and Driffield curves, (2) modulation transfer functions by using the slit method, and (3) noise Wiener spectra. Subjective clinical assessment showed that the images obtained with ultrarapid processing were acceptable, with increased contrast and graininess. Hurter and Driffield curve measurements confirmed higher gradients. Modulation transfer function measurements were the same as for the conventional films. Noise Wiener spectrum measurements showed a 10% increase in noise for MGH SR vs TMG film and a 30% increase for MGL-SR vs OC film. We conclude that acceptable image quality can be obtained using ultrarapid processing, with processing time approximately 60% that of conventional rapid processing. Potential applications include all areas in which rapid availability of the radiograph for interpretation is important. Although the processor studied was the first of its kind available, our evaluation indicates that the technology is available for a new class of ultrarapid processors. PMID- 2108554 TI - The radiology manpower equation: a new look. PMID- 2108555 TI - Quality improvement in diagnostic radiology. PMID- 2108556 TI - Perception of radiologic images. PMID- 2108557 TI - Please be specific. PMID- 2108558 TI - Tracheal rupture. PMID- 2108559 TI - Hydrostatic reduction of intussusception. PMID- 2108560 TI - Bile duct necrosis after partial hepatectomy and transcatheter hepatic arterial embolization. PMID- 2108561 TI - Periportal lymphedema in trauma patients. PMID- 2108562 TI - Confusing similarities between peripancreatic retroperitoneal lymphangioma and other lesions. PMID- 2108563 TI - Renal imaging in long-term dialysis patients: a comparison of CT and sonography. PMID- 2108564 TI - Multiple hydatid cysts. PMID- 2108565 TI - CT of the wrist: what is abnormal? PMID- 2108566 TI - Bone scan screening for occult fractures of carpals and metacarpals. PMID- 2108567 TI - Hanson lecture. Adrenal imaging: current status. PMID- 2108568 TI - MR angiography. PMID- 2108569 TI - Physiology and radiology of the normal oral and pharyngeal phases of swallowing. PMID- 2108570 TI - Radiologic assessment of abnormal oral and pharyngeal phases of swallowing. PMID- 2108571 TI - Comparison of Biello, McNeil, and PIOPED criteria for the diagnosis of pulmonary emboli on lung scans. AB - The McNeil, Biello, and newly proposed PIOPED (from the National Institutes of Health-sponsored study, Prospective Investigation of Pulmonary Embolism Detection) interpretive methods for detection of pulmonary embolism on lung scans were compared in 96 patients who also underwent pulmonary angiography. Segmental findings on 99mTc perfusion and aerosol ventilation scans, chest radiographs, and pulmonary angiograms obtained within 48 hr of each other were encoded along with other information into a data base to facilitate analysis. The McNeil, Biello, and PIOPED criteria were applied to the encoded data. Although the PIOPED set of criteria yielded the most favorable likelihood ratio for predicting an angiogram showing pulmonary emboli and a favorable likelihood ratio for predicting an angiogram not showing pulmonary emboli, it had the highest number of indeterminate studies. The McNeil criteria demonstrated the least favorable likelihood for predicting pulmonary emboli on an angiogram. The Biello and McNeil criteria showed the most favorable likelihood ratio for predicting an angiogram not showing pulmonary emboli. Analysis of receiver-operating-characteristic (ROC) curves yielded the greatest area under the ROC curve for the Biello criteria, but there were no statistically significant differences among the three sets of criteria. This study suggests that the Biello scheme represents the best compromise of the sets of criteria studied. PMID- 2108572 TI - Bronchiolitis obliterans organizing pneumonia: CT features in 14 patients. AB - Bronchiolitis obliterans organizing pneumonia is a disease characterized by the presence of granulation tissue within small airways and the presence of areas of organizing pneumonia. We retrospectively reviewed the chest radiographs, CT scans, and biopsy specimens in 14 consecutive patients with proved bronchiolitis obliterans organizing pneumonia. Six patients were immunocompromised because of leukemia or bone-marrow transplantation. In all patients, 10-mm collimation CT scans were available. In 11 of the 14 patients, select 1.5-mm scans were obtained. The CT findings included patchy unilateral (n = 1) or bilateral air space consolidation (n = 9), small nodular opacities (n = 7), irregular linear opacities (n = 2), bronchial wall thickening and dilatation (n = 6), and small pleural effusions (n = 4). All patients had areas of air-space consolidation, small nodules, or both. A predominantly subpleural distribution of the air-space consolidation was apparent on the radiographs of two patients and on CT scans of six. Pathologically, the nodules and the consolidation represented different degrees of inflammation in bronchioles, alveolar ducts, and alveoli. Although most of the findings were apparent on the radiographs, the CT scans depicted the anatomic distribution and extent of bronchiolitis obliterans organizing pneumonia more accurately than did the plain chest radiographs. PMID- 2108573 TI - Laryngeal chondrosarcoma: CT findings in three patients. PMID- 2108574 TI - Wooden foreign body in the lung parenchyma. PMID- 2108576 TI - Physiologic role of coronary PGI2 and PGE2 in modulating coronary vascular response to sympathetic stimulation. AB - To investigate a physiologic role of coronary prostacyclin (PGI2) and prostaglandin E2 (PGE2) 30 patients who were not affected by coronary heart disease were evaluated for coronary hemodynamics and coronary PGI2 and PGE2 production. Inhibition of coronary prostaglandin biosynthesis by ketoprofen (1 mg/kg) or aspirin (15 mg/kg) administered intravenously did not significantly change coronary hemodynamics in resting conditions. In all patients cold pressor tests induced significant increases in coronary blood flow (p less than 0.001) and decreases in coronary vascular resistance (p less than 0.001) without changes in cardiac oxygen extraction and with consequent increases in calculated myocardial oxygen consumption. Simultaneously, a marked increase in coronary PGI2 (as 6-keto-PGF1 alpha) and PGE2 formation was observed (p less than 0.001). Both ketoprofen (1 mg/kg) and aspirin (15 mg/kg) administration completely abolished PGI2 and PGE2 formation that was induced by cold pressor test and caused a paradoxical increase in coronary vascular resistance (ketoprofen: p less than 0.02; aspirin: p less than 0.05). The results of this study support a physiologic role for the coronary prostaglandins in modulating coronary vascular response to sympathetic stimulation in nonischemic patients. PMID- 2108577 TI - Hyperventilation-induced coronary vasospasm refractory to intracoronary nitroglycerin. PMID- 2108575 TI - One-year outcome after therapy with tissue plasminogen activator: report from the Thrombolysis and Angioplasty in Myocardial Infarction trial. AB - To evaluate the long-term effects of reperfusion with tissue plasminogen activator (t-PA) and an aggressive strategy of revascularization with angioplasty and coronary artery bypass grafting, we obtained 1-year follow-up results from 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI I) trial. All patients were treated with 100 to 150 mg of t-PA intravenously over 6 to 8 hours, and coronary angiography was performed within 90 minutes of initiation of therapy. In 197 patients with suitable anatomic characteristics, angioplasty was either performed immediately or was deferred for 7 to 10 days on a randomized basis. The remainder of the patients were treated as considered clinically appropriate. The in-hospital mortality rate was 7%, and only 1.9% of patients died in the first year after discharge from the hospital; three patients died of cardiac events and four died of noncardiac causes. Ninety-four percent of patients discharged alive from the hospital remained alive and had no myocardial infarctions during the first 12 posthospital months. Revascularization procedures after discharge from the hospital included angioplasty in 8% of patients and coronary artery bypass grafting in 5%. The high survival rates were evident in high-risk groups defined by age, ejection fraction, and extent of coronary artery disease. At 1-year follow-up 64% of patients less than 65 years of age were employed and only 10% reported that they were disabled; 94% of patients were in Canadian Heart Association class I or II. These low rates of follow-up events suggest a change in the "natural history" of the first year after acute myocardial infarction. PMID- 2108578 TI - Calorie and protein provision for recovery from severe burns in infants and young children. AB - Severely burned adults increase their metabolic energy expenditure (MEE) to levels approaching twice the normal resting metabolic rate (RMR). There are no available measurements of MEE for severely burned infants and toddlers, however, and nutritional support relies on published estimates of MEE that range from 200% to 400% of RMR. We determined the actual calories provided to 10 infants and children ages 3-33 mo during acute care for severe burns (59 +/- 5% total-body surface burn). Our standard protocol emphasizes the delivery of amino acids at 3 g.kg-1.d-1 in conjunction with prompt excision and grafting. An anabolic state characterized by weight maintenance and healing was supported with far fewer calories than predicted by four published formulas for MEE. We conclude that when greater than 2.5 g.kg-1.d-1 protein is provided, efficient protein utilization for recovery is achieved with calorie provision at 120-200% RMR in severely burned infants and toddlers. PMID- 2108579 TI - Serum myoinositol concentrations in premature infants fed human milk, formula for infants, and parenteral nutrition. AB - Myoinositol concentration was studied in serum of 65 neonates and their mothers at the time of birth, in samples of various types of feedings for infants, and in serial serum samples of 15 premature infants receiving human milk, formulas for infants, or parenteral nutrition over a 3-wk period. At birth the serum concentration of myoinositol was greater in neonates than in their mothers (108 +/- 10 vs 52 +/- 6 mumol/L, respectively, means +/- SEM, p less than 0.01). In feedings for infants, the concentrations of myoinositol were significantly greater in human milk than in formulas or parenteral nutrition solutions (1840 +/ 451 vs 420 +/- 110 vs 100 +/- 8 mumol/L, respectively, p less than 0.001). Over a 3-wk period the serum concentration of myoinositol increased in infants receiving human milk but not in those receiving formulas or parenteral nutrition. Serum concentrations of myoinositol in neonates are greater than in adults and are directly influenced by myoinositol intake. PMID- 2108580 TI - Fecapentaene excretion: aspects of excretion in newborn infants, children, and adult normal subjects and in adults maintained on total parenteral nutrition. AB - People in developed nations such as the United States and Canada have an increased risk of colon cancer. Fecal mutagens have been detected in the feces of individuals at high risk for colon cancer. We describe a rapid, sensitive, reliable, reproducible high-pressure liquid chromatography (HPLC) method for detecting fecapentaenes, the most active and chief mutagen found in human stool. We found fecapentaene in all the stool samples of adults on typical high-fat, low fiber Western diets. These fecapentaene concentrations remained largely constant when subjects consumed constant diets. Fecapentaene concentrations were reduced for total-parenteral-nutrition (TPN) patients with severe intestinal malabsorption. This finding with TPN patients may reflect changes in important variables of gut microflora in fecapentaene production. Studies with newborns and children showed that fecapentaenes appeared very early in life but are not present in stool at birth. PMID- 2108581 TI - Testing the blood supply for non-A, non-B hepatitis. A nonspecific approach for improving transfusion safety has a heterogeneous impact on blood donors. PMID- 2108582 TI - Acute renal insufficiency due to renal infarctions in a patient with neurofibromatosis. AB - Manifestations of neurofibromatosis in the skin, the eye, and the skeletal and nervous systems have been well documented since the disease was first described in 1882. Stenosing vascular lesions as complications of neurofibromatosis were first reported in 1945. They are being increasingly recognized and most commonly involve the renal artery. Renal artery stenosis (usually proximal), intraparenchymal renal arterial abnormalities, and coarctation of the abdominal aorta often lead to hypertension. However, despite reports of bilateral and severe renal artery disease, renal infarction and resulting renal insufficiency have not been described. We present the case of a 35-year-old woman with neurofibromatosis and chronic hypertension associated with narrowing of right intrarenal arteries. The patient had two separate episodes of left renal infarction documented clinically and radiographically. The second infarct resulted in renal insufficieny. There was no hypercoagulopathy or source for embolism. This case suggests that renal infarction and renal insufficiency are additional complications of neurofibromatosis. PMID- 2108583 TI - Postpartum hypopituitarism with preservation of the pituitary-ovarian axis. AB - An 18-year-old woman developed postpartum hypopituitarism, presenting with personality and behavioral changes caused by severe hypoglycemia. In spite of well-documented deficiencies of thyroxine, cortisol, and growth hormone, she maintained normal ovarian function (reflected by normal menstrual cycles, normal estrogenization on examination, and normal FSH and estradiol levels). Classically, gonadal failure occurs very early in the course of pituitary failure, prior to loss of thyroid or adrenal function; preserved ovarian function is commonly used as clinical evidence of intact pituitary function. This patient emphasizes the importance of pursuing the possibility of pituitary disease in appropriate clinical settings, even in patients with intact ovarian function. PMID- 2108584 TI - Unsustained central sexual precocity in four girls. AB - Four girls who presented with breast enlargement at 4-5.8 years of age have been followed without specific therapy for up to 4 years. Three had normal CT brain scans, one had normal skull and sella x-rays. Stimulation of gonadotropins by LHRH was excessive in all but plasma estradiol levels were only intermittently elevated. Initially, bone age was advanced and height velocity was increased in three of the four. Ultrasound visualized an enlarged uterus in two and waxing and waning ovarian cysts in all. The clinical course was characterized by persistence of physical signs over at least 3.4 years in one patient, fluctuation in another, and marked regression in two. We propose that some patients with central precocious puberty may spontaneously have a nonprogressive course which has to be considered when evaluating the efficiency of drugs interfering with puberty. PMID- 2108585 TI - Tonsillectomy under local anesthesia: a safe and effective alternative. AB - Tonsillectomy using local anesthesia (local tonsillectomy) is a safe and effective alternative to general anesthesia in the healthy cooperative teenage or adult patient. This retrospective analysis involved 64 local tonsillectomies performed over the past 7 years in a minor operating room using only local anesthesia with intravenous sedation. Operations were performed by residents in training as well as by experienced head and neck surgeons. Blood loss, morbidity, complications, and patient satisfaction were reviewed and compared with tonsillectomies done under general anesthesia. The average blood loss was 42 mL in the local tonsillectomy group with no cases of postoperative hemorrhage, compared with 198 mL in the general anesthesia group with two cases of postoperative hemorrhage. There was one major complication related to postoperative antibiotic use in the local anesthesia group, and follow-up interviews revealed that patients were satisfied with the procedure and would recommend and choose local anesthesia again. We conclude that local tonsillectomies have high patient acceptance and are associated with minimal morbidity and complications. Furthermore, they are cost-effective. PMID- 2108586 TI - The Bain, ADE, and Enclosed Magill breathing systems. A comparative study during controlled ventilation. AB - The Enclosed Magill, Humphrey ADE and the Bain breathing systems are all used for controlled ventilation of the lungs. This study compares the three systems in vitro with a lung model and in clinical practice. No difference was observed, with ventilatory variables commonly used in clinical practice, between the Bain and the ADE, while significantly lower end-tidal carbon dioxide values were observed with the Enclosed Magill (about 7%). Lower fresh gas flows can be used under these circumstances to maintain normocapnia with the Enclosed Magill than either the Bain or the Humphrey ADE. PMID- 2108587 TI - High-performance liquid chromatographic method for determination of hypusine and deoxyhypusine. AB - A selective and sensitive reversed-phase high-performance liquid chromatographic method is described for the determination of the amino acid hypusine which occurs ubiquitously in mammalian cells and for the simultaneous measurement of its immediate precursor deoxyhypusine. These amino acids, after their ion-exchange separation from the bulk of other amino acids in protein hydrolysates, are derivatized with o-phthalaldehyde and the fluorescent derivatives are separated by reverse-phase liquid chromatography. The sensitivity of this method allows detection of less than 5 pmol of each of these unusual amino acids. The method is applied to the determination of hypusine and deoxyhypusine in acid hydrolysates of cultured cells and tissues. PMID- 2108588 TI - Heterogeneity among membrane vesicles of Escherichia coli: effects of production and fractionation techniques. AB - We have previously shown that Escherichia coli membrane proteins are associated with subpopulations of membrane vesicles beyond the well-defined inner versus outer membrane classification. To separate these vesicles we used a shallow sucrose gradient which differed in many respects from established procedures. Here we compare this revised technique to the classical sucrose density centrifugation procedure. We found that certain manipulations common to the latter obscured heterogeneity among membrane vesicles. The following treatments degraded vesicle separation: growth in rich medium addition of EDTA to buffers, spheroplasting, sonication, pelleting of membranes prior to sucrose gradient centrifugation, overloading the gradient, and long centrifugation times. Some treatments, such as EDTA addition, affected only selected vesicles. When determining protein localization within bacterial membranes experiments should be designed to avoid or at least minimize these manipulations. PMID- 2108589 TI - A paper membrane filter assay for ciliate chemoattraction. AB - A quantitative bioassay for ciliate chemoattraction based on the Boyden assay is described with the ciliates Tetrahymena thermophila and Tetrahymena pyriformis as test organisms. A chamber is separated into two compartments by a Whatman 3MM filter, and a suspension of starved cells (approximately 10(5) cells/ml) is placed in one compartment and a solution containing attractant in the other. The gradient of chemoattractant across the filter causes the cells to swim through the filter into the attractant-containing compartment where their appearance is determined by electronic cell counting. The assay described is convenient with a signal-to-noise ratio of approximately 10. It is shown here to work with the attractants proteose peptone and platelet-derived growth factor. PMID- 2108590 TI - Airway fire during co2 laser surgery using a Xomed Laser endotracheal tube. PMID- 2108591 TI - Hemodynamic effects of epinephrine, dopamine, nitroglycerin, and nitroprusside in a patient with a total artificial heart (TAH). PMID- 2108592 TI - Intestinal permeability in irritable bowel syndrome. Effect of diet and sodium cromoglycate administration. AB - We studied 14 patients with irritable bowel syndrome for the presence of increased intestinal permeability to food antigens and their responses to diet with and without disodium cromoglycate. After a standardized oral challenge with cow milk, serum beta-lactoglobulin was increased above control values in three patients. This finding did not correlate with response to hypoallergenic diet or treatment with disodium cromoglycate for 3 weeks. However over 50% of patients improved after diet with and without DSCG (2/5 on diet only and 5/7 with disodium cromoglycate of 12 evaluable cases). Since only two patients had elevated serum IgE levels, our results suggest that intolerance rather than hypersensitivity to foods may play a role in the disease. The tests we used to identify immunologic mechanisms could not predict which patients would do better on the diet and/or the drug. PMID- 2108593 TI - Hereditary angioedema: therapeutic effect of danazol on C4 and C1 esterase inhibitors. AB - Hereditary angioedema (HAE) is an inherited deficiency of C1 esterase inhibitor (C1 inh). The two types of genetic C1 inh deficiency are type I, which is quantitative, and type II, which is functional. For the purpose of the present study, four HAE patients were selected. None of them had received any androgenic therapy. The group included three type I and one type II cases. All patients that entered the protocol received danazol, 400 mg/day for 14 days. The complement system was evaluated by monitoring C4, hemolytic complement 50% (CH50), circulating immune complexes (CIC), and antigenic and functional C1 inh during the study. The level of complement factors at the beginning and at the end of this period demonstrated a statistically significant increase in C4 and CH50 and the disappearance of CIC, while C1 inh remained unmodified. These results suggest that the therapeutic effect of danazol may have two mechanisms of action: (1) promotion of C4 synthesis by anabolic effect resulting in an improvement of the complement system with the disappearance of CIC and (2) a minor increase in C1 inh level primarily due to the lack of its consumption. PMID- 2108594 TI - Effect of epinephrine on end-tidal carbon dioxide monitoring during CPR. AB - End-tidal carbon dioxide (ETCO2) has been shown to correlate with coronary perfusion pressure (CPP) during CPR and has been proposed as a useful noninvasive monitor of CPR efficacy. The effects of therapeutic epinephrine dosing on ETCO2 and CPP in six dogs were examined. Ventricular fibrillation was induced and left untreated for five minutes before CPR was initiated. After five minutes of CPR, epinephrine 0.045 mg/kg IV was administered. CPP and ETCO2 were compared immediately before and two minutes after epinephrine administration. There was a significant increase in CPP from 12.2 +/- 9.6 to 26.8 +/- 7.1 mm Hg (P = .006) after epinephrine. This was accompanied by a significant decrease in ETCO2 from 8.2 +/- 2.9 to 3.8 +/- 2.0 mm Hg (P = .01). These data indicate that after epinephrine administration, caution must be exercised in using ETCO2 as an indicator of CPP. PMID- 2108595 TI - Lead poisoning in adults from renovation of an older home. AB - Presented is the case of a group exposure to lead occurring during the removal of lead-based paint from an older home. One patient had symptoms from the time of exposure to the time of presentation, when he was acutely ill and encephalopathic. The patient was treated successfully with an initial course of British Anti-Lewisite agent and calcium disodium versenate (CaEDTA) chelation, and two subsequent chelations with CaE-DTA alone. The other two patients had elevated lead levels but were asymptomatic. They were followed closely, and their lead levels steadily declined over several months. The evaluation and treatment of lead poisoning and excessive lead levels in adults is discussed, as is the need for physicians and the lay public to become aware of the hazards of renovating older homes. PMID- 2108596 TI - The Pepper Commission: looking at access and long-term health care issues. PMID- 2108597 TI - Opportunities in long-term care. PMID- 2108598 TI - As I see it. Long-term care needs creative nurses. PMID- 2108599 TI - New rules are two-edged sword. PMID- 2108600 TI - Long-term care nurses offer ideas, tips. PMID- 2108601 TI - [Rhesus phenotype and lymphocyte subpopulations]. AB - Lymphocyte subpopulations identified by OK3, OK4 and OK8 monoclonal antibodies were studied as a function of certain Rh markers in 2 groups of subjects: 47 children and adolescents with proven reaginic IgE-dependent allergies and 29 healthy adult controls. The Rh antigens C and c were evaluated in their 3 possible configurations: CC, Cc and cc. In both groups studied, the same significant distribution was observed. Allergic cc subjects had the most CD4+ lymphocytes (43.4%) versus CC (34%) and Cc (33.7%), as compared to control cc (42.05%), CC (36.1%). The possible clinical implications of these findings are discussed. PMID- 2108602 TI - [Evan's syndrome and pseudolupic circulating anticoagulants during endocarditis with Q fever]. PMID- 2108603 TI - Chromosomal mapping of a human phenol UDP-glucuronosyltransferase, GNT1. AB - A 5' fragment of a full-length cDNA clone encoding a human phenol UDP glucuronosyltransferase was used to produce a specific probe for this gene. DNA isolated from a panel of 18 human-rodent somatic cell hybrids was analysed by Southern-blot hybridization. The results indicate that this UDP glucuronosyltransferase is encoded by a single gene, designated GNT1, located on human chromosome 2. PMID- 2108604 TI - Ganglioside biosynthesis in rat liver: different distribution of ganglioside synthases in hepatocytes, Kupffer cells, and sinusoidal endothelial cells. AB - The activities of five glycolipid-glycosyltransferases, GL2, GM3, GM2, GM1, and GD1a synthase, were determined in a cell-free system with homogenate protein of total rat liver, isolated hepatocytes, Kupffer cells, and sinusoidal endothelial cells. In rat liver parenchymal and nonparenchymal cells ganglioside synthases were distributed differently. Compared to hepatocytes, Kupffer cells expressed a nearly sevenfold greater activity of GM3 synthase, but only 14% of GM2, 19% of GM1, and 67% of GD1a synthase activity. Sinusoidal endothelial cells expressed a pattern of enzyme activities quite similar to that of Kupffer cells with the exception of higher GM2 synthase activity. Activity of GL2 synthase was distributed unifromly in parenchymal and nonparenchymal cells of rat liver, but differed by sex. It was 1 to 2 orders of magnitude below that of all the other ganglioside synthases investigated. The results indicate GL2 synthase regulates the total hepatic ganglioside content, and hepatocytes but not nonparenchymal liver cells have high enzymatic capacities to form a-series gangliosides more complex than GM3. PMID- 2108605 TI - Chromatographic separation of activated and unactivated forms of aldose reductase. AB - Chromatography of bovine kidney aldose reductase using Matrex Orange A affinity gel results in the separation of the unactivated and activated enzyme forms. The former washes through the column, while the latter is eluted with an NADPH step gradient. The separated enzyme forms display Vmax and Km glycolaldehyde values, and relative sensitivities to inhibition by the aldose reductase inhibitor AL 1576 (spiro[2,7-difluorofluorene-9,4'-imidazolidine]-2',5'- dione), that are similar to those reported previously for the individual forms. However, because Vmax is 17-fold lower for the unactivated enzyme, the purification of aldose reductase via NADP(H) elution from a dye-ligand affinity matrix can result in the selective purification of only the activated enzyme form. These results have direct implications for the study of potential aldose reductase inhibitors, and may explain why linear double-reciprocal plots are commonly observed for enzyme prepared in this manner, while nonlinear plots are seen in other cases. PMID- 2108606 TI - Polyamine regulation of the synthesis of thymidine kinase in bovine lymphocytes. AB - Concanavalin A-activated lymphocytes were made polyamine deficient by treatment with alpha-difluoromethylornithine and ethylglyoxal bis(guanylhydrazone). Thymidine kinase activity in polyamine-deficient cells was 17% of the level in normal cells. Thymidine kinase mRNA increased with time after concanavalin A activation and reached a maximum at 36 h after concanavalin A addition. The amount of thymidine kinase mRNA in polyamine-deficient cells was approximately 75% of that in normal cells. The transcription of thymidine kinase gene in isolated nuclei of polyamine-deficient cells was also 75% of that from normal cells. The turnover rate of thymidine kinase mRNA in both normal and polyamine deficient cells was nearly equal. In normal cells, 95% of thymidine kinase mRNA was polysome associated, while in polyamine-deficient cells, 60% of the mRNA was polysome associated. In addition, the size of polysomes associated with thymidine kinase mRNA in polyamine-deficient cells was smaller than that in normal cells. Synthesis of thymidine kinase was stimulated approximately seven-fold by 0.3 mM spermidine in a rabbit reticulocyte polyamine-free protein synthetic system. The half-life of thymidine kinase activity in both normal and polyamine-deficient cells was nearly equal. Thymidine kinase activity was not influenced significantly by 0.3 mM spermidine. These combined results suggested that the synthesis of thymidine kinase was mainly regulated by polyamines at the level of translation. PMID- 2108607 TI - Enhancement of hydroperoxide-dependent lipid peroxidation in rat liver microsomes by ascorbic acid. AB - Simultaneous addition of ascorbic acid and organic hydroperoxides to rat liver microsomes resulted in enhanced lipid peroxidation (approximately threefold) relative to incubation of organic hydroperoxides with microsomes alone. No lipid peroxidation was evident in incubations of ascorbate alone with microsomes. The stimulatory effect of ascorbate on linoleic acid hydroperoxide (LAHP)-dependent peroxidation was evident at all times whereas stimulation of cumene hydroperoxide (CHP)-dependent peroxidation occurred after a lag phase of up to 20 min. EDTA did not inhibit CHP-dependent lipid peroxidation but completely abolished ascorbate enhancement of lipid peroxidation. Likewise, EDTA did not significantly inhibit peroxidation by LAHP but dramatically reduced ascorbate enhancement of lipid peroxidation. The results reveal a synergistic prooxidant effect of ascorbic acid on hydroperoxide-dependent lipid peroxidation. The inhibitory effect of EDTA on enhanced peroxidation suggests a possible role for endogenous metals mobilized by hydroperoxide-dependent oxidations of microsomal components. PMID- 2108608 TI - [Enhancing hyperthermic cytotoxicity in Walker-256 by intraarterial injection of warmed saline]. AB - The tumor growth of Walker-256 implanted sc. on dorsum side of hindpaw of Wistar rat were suppressed by warmed (43 degrees C) water immersion. Antitumor effects of hyperthermia were increased by injection (a.i.) of saline mixed with noradrenaline (5 mcg). Although tumors in advanced stage group (D-8) are larger in size and more tumor vascularity than in early stage group (D-4), hyperthermic cytotoxicity were observed in D-8 but not observed in D-4. The hyperthermic energy injured the tumor vessels, which failed to flow the blood to the tumor cells and resulted in sever cytotoxic damage of Walker-256. Therefore, cytotoxic damage could be enhanced by injecting warmed water (43 degrees C) into tumor vessels after chemotherapy (MMC; 0.5 mg/kg) in D-8. Metastatic liver cancer was treated with thermochemotherapy. 5% of glucose warmed (43 degrees C) mixed with 0.1 mg of noradrenaline and heparin was administered into hepatic artery after chemotherapy (2 to 6 mg of MMC a.i.). PMID- 2108609 TI - [Fundamental and clinical studies of changes in endocrine conditions in cancer patients]. AB - The aim of the present study was to investigate hypothalamic-pituitary function, pituitary-thyroid function as well as pituitary-adrenal function in cancer patients. 1. Hypothalamic-pituitary function: We already reported a tumor-related paradoxical increase of serum growth hormone (GH) in oral glucose tolerance test (OGTT) and TRH test, which seemed to be due to changes in pituitary GH cell, not hypothalamus. The high incidence of the paradoxical increase of GH in OGTT was found in patients with hepatocellular cancer and pancreatic cancer, whereas in TRH test it was observed in patients with pancreatic, colonic and gastric cancer. The highly sensitive GH enzyme immunoassay demonstrated in 12 non-responder patients in OGTT a significant reduction of serum GH at 30 minutes compared to basal values. 2. Pituitary-thyroid function: We already demonstrated that a high incidence of low T3 syndrome in elderly cancer patients compared to younger patients and metabolic changes in glucose must be involved in the pathogenesis. In addition, this syndrome is significantly related to prognosis. There were no significant changes in thyroid function before and after curative operation for tumors except in patients with poor prognosis. 3. Pituitary-adrenal function: It was shown that cancer cachexia is characterized by hypercortisolemia, which must be due to a defect of negative feedback control. PMID- 2108610 TI - [Methodological aspects on the histological evaluation of subrenal capsule assay (SRCA)]. AB - For the purpose to establish the reliability of SRCA using clinical materials, a histological assessment under the suppression of host reaction was introduced; 1) for the immune suppression cyclosporin A (CsA) was used, 2) to overcome the heterogeneity of fragments, the numbers of implants were increased to ten per group (two pieces/kidney), 3) time flame was 6 days as original, 4) the amounts of drugs were essentially similar to those of Bogden's original method. Drugs solely enough to induce immunosuppression such as 5-FU, CPA and MTX were administered by themselves and those not enough such as MMC, ADM and CDDP were done with least enough usage of CsA, 5) histological changes were analysed from three factors such as grade of degeneration (5 grades), tumor cell amounts (3 grades) and numbers of mitosis (3 grades). The histological analysis form representing the numbers of implants of each group on the indicated places by the individual grades of those 3 factors was devised. With this form, chemosensitivity results were expressed as ++, +, +/- and -. In a panel of more than one +/- results a sensitivity ranking was put on. 5) Macroscopic assessment was made by the measurement of height of the implants at day 6 for simplicity only for future relevance. This method of histological SRCA was applied on one parotid, one pancreas and ten colon cancers where viable tumor cells with frequent mitosis were seen in the CsA treated control groups and, on the other hand, occasional apparent degenerations were observed in some of drug treated groups. These facts verified that this histological assessment was practical and rational and covers the disadvantage of macroscopic findings. PMID- 2108611 TI - [Relationship between antitumor activity and the inhibition of thymidylate synthase after oral administration of UFT in nude mice bearing human tumor]. AB - We studied the relationship between antitumor efficacy of UFT, which is a most widely used drug among fluorinated pyrimidines recently, and its effect on the content and the inhibition rate of thymidylate synthase (TS) in 15 human tumor xenografts derived from stomach, colon, breast and pancreatic cancer patients. There was a linear relationship between the content of TS and tumor mass doubling time (MDT). It may be shown that TS content reflects the growth rate of tumor cells. It should be stressed that tumor growth inhibition rate (TGIR), induced by UFT, correlated well with the inhibition of TS (TSI), particularly in the stomach and breast cancer. These results demonstrate that the measurement of inhibition rate of TS is important for the prediction and evaluation of clinical efficacy of UFT. PMID- 2108612 TI - [In vitro combined effects of pirarubicin (THP) and various antitumor drugs on human tumor cell lines]. AB - The combined effects of pirarubicin (THP) and various antitumor drugs on HeLa S3 human uterine cervix carcinoma and K562 human myelocytic leukemia cells were determined by enhancement of their cytotoxic activities. The combination of 0.15 microgram/ml THP with cisplatin (CDDP), mitomycin C (MMC), peplomycin (PEP), 5 fluorouracil (5-FU), methotrexate (MTX), enocitabine (BH-AC) or etoposide showed synergistic effects on HeLa S3 cells. Also, the combination of 0.01 microgram/ml THP with CDDP, BH-AC or etoposide showed synergistic effects on K562 cells. Especially, the combined effects of THP with MMC or MTX were remarkable, and the combination under almost all concentrations of MMC or MTX showed synergistic effects on HeLa S3 cells. On the other hand, the combination of adriamycin (ADM) with MMC or MTX did not show such a remarkable effects on HeLa S3 cells. PMID- 2108613 TI - [The effect of cepharanthin on adjuvant chemotherapy induced bone marrow suppression in patients with breast cancer]. AB - We studied the effect of Cepharanthin on bone marrow suppression induced by adjuvant chemotherapy in primary breast cancer patients in our hospital. The 36 patients with breast cancer were divided into two groups. Both groups were administered of MMC 20 mg intravenously on the day of radical operation. One group (23 patients) was administered of Cepharanthin 60 mg every day, but the other (13 patients) group was not administered. In the leukocyte count at 3 weeks after post operation, 82.6% (19 out of 23) of the patients who were administered cepharanthin kept more than 70% of pre-operation's leukocyte. On the other hand, only 46.1% (6 out of 13) of the patients who were not administered Cepharanthin kept more than 70% of pre-operation's leukocyte. The number of thrombocyte was not decreased in both groups. Side effects by Cepharanthin were not observed in this study. PMID- 2108614 TI - [Treatment with UFT as surgical adjuvant chemotherapy in carcinoma of large intestine. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan]. AB - The therapeutic results of the method II of the second study of the Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan were retrospectively reviewed and the relations of the 3-year survival rate to the dose of UFT per body weight as well as per kg of the patient and discontinuation of the treatment with UFT were investigated. The dose per day of UFT was randomly divided into group C (treated with UFT 600 mg/body/day) and group D (treated with UFT 400 mg/body/day for 12 months) by the envelope method. The 3-year survival rate of the patients whose body weight was 50 kg or more was higher than in the patients weighting less than 50 kg. The 3-survival rate of the patients treated with UFT from 8 to less than 12 mg/kg was the highest, while that of the patients treated with UFT of more than 12 mg/kg was the lowest. However, no statistical difference was observed between the two groups. The same results were observed in carcinoma of the colon and rectum, respectively. The findings indicated that the administration of excess amount of UFT was not effective. The relation between the 3-year survival rate and discontinuation of treatment with UFT was investigated at 6, 9 and 12 months after administration with UFT. The prognostic background factors of the C-group and the D-group were compared, but no difference was observed between the 2 groups at 9 months after administration. The 3-year survival rate of the patients treated continuously with UFT was higher than that of discontinued administration. The difference was especially evident in carcinoma of the colon, and good results were observed in cases treated continuously than in discontinued cases in both C- and D-groups. PMID- 2108615 TI - Pathogenesis of paraneoplastic follicular hyperkeratotic spicules in multiple myeloma. Follicular and epidermal accumulation of IgG dysprotein and cryoglobulin. AB - We describe a 62-year-old man with multiple myeloma who developed horny spicules on his face, particularly on his nose. IgG-lambda monoclonal gammopathy was detected, and the serum dysprotein was shown to be a cryoglobulin, which forms a cryogel at low temperatures. Light and electron microscopic and immunohistochemical examinations showed an intercellular precipitation and massive accumulation of the IgG dysprotein and cryoglobulin between the keratinocytes of the upper epidermis and the infundibular epithelium. The follicles were dilated and filled with parakeratotic cells, the protein deposits between them and a rudimentary hair thus resulting in the clinically visible symptoms of horny spicules. The limitation or the predominance of the symptoms in cold-exposed body regions, the morphological identification of the dysprotein deposits as cryoglobulin or cryogel, and the laboratory findings concerning the temperature and pH dependence of the precipitation of the IgG dysprotein reveal that the paraneoplastic horny spicules are a hitherto unknown clinical manifestation of cryoglobulinemia. PMID- 2108616 TI - Nevus spilus with malignant melanoma in a patient with neurofibromatosis. PMID- 2108617 TI - Late-onset neurofibromas developed in a patient with psoriasis vulgaris during PUVA treatment. PMID- 2108618 TI - An ecotoxicological study of a population of the white footed mouse (Peromyscus leucopus) inhabiting a polychlorinated biphenyls-contaminated area. AB - White footed mice (Peromyscus leucopus) inhabiting an area surrounding a pond (Tyler) contaminated with polychlorinated biphenyls (PCBs) and metals (Cadmium, Zinc, Copper) had whole body burdens of 0.42-4.17 ppm PCBs (mean 2.3 ppm) and animals from a comparison nonpolluted site (WCC) had no detectable PCBs. Males and females caught at the polluted site in the winter months were not significantly different in body weight or length when compared to WCC animals, but Tyler animals had significantly increased relative liver, kidney, spleen and adrenal weights. In the summer months, mostly males were caught at both Tyler and WCC sites. Tyler males were significantly lighter than WCC males, and had a significantly increased relative liver weight when compared to the males from the WCC site. In addition, the adult Tyler males had significantly lower relative testis weights. At Tyler there was a significantly smaller proportion of juveniles and subadults in the population than at WCC. Polychlorinated biphenyls levels in the adult Tyler males were significantly positively correlated with relative liver weight, but there were no significant correlations with any of the other structures measured. These results suggest that at the polluted site there is inhibition of reproduction and changes in liver, spleen, adrenal, and testis function. PMID- 2108619 TI - Renal artery thrombosis and hypertension in a 13 year old girl with antiphospholipid syndrome. AB - The case of a 13 year old girl with renal artery thrombosis and hypertension is described. A cerebrovascular accident and a probable occlusion of the superior mesenteric artery also occurred. Very high levels of 'lupus anticoagulant', anticardiolipin antibodies as well as false positive Venereal Disease Research Laboratory tests were repeatedly shown. Moreover, the patient fulfilled at least four classification criteria for systemic lupus erythematosus, but only a slight positivity for antinucleolar antibodies was present. The striking relation between antiphospholipid antibody levels and clinical events and the treatment of this complex syndrome are discussed. PMID- 2108620 TI - Occlusive ocular vascular disease and antiphospholipid antibodies. PMID- 2108621 TI - Bacterial translocation and intestinal atrophy after thermal injury and burn wound sepsis. AB - Bacterial translocation (BT) occurs after thermal injury in rodents in association with intestinal barrier loss. Infection complicating thermal injury may also affect the intestine producing bowel atrophy. To study these relationships, Wistar rats received either 30% scald followed by wound inoculation with Pseudomonas; 30% scald with pair feeding to infected animals; or sham injury as controls. On days 1, 4, and 7 after injury animals were killed with examination of the bowel and culture of the mesenteric lymph nodes (MLN), livers, spleens, and blood. All burned animals demonstrated BT to the MLN on day 1 after injury, but only burn-infected animals had continued BT on days 4 and 7, with progression of BT to the abdominal organs and blood. Burn injury and infection also resulted in significant atrophy of small bowel mucosa temporally associated with continued BT. Thus injury complicated by infection results in prolonged and enhanced bacterial translocation, perhaps due to failure to maintain the mucosal barrier. PMID- 2108623 TI - [Chronology and incidence of restenosis after coronary angioplasty. Comparison of patients with stable and unstable angina]. AB - The aim of this prospective study was to compare the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA) in patients with stable and unstable angina before the procedure. Between January 1984 and February 1986, 344 patients with stable angina and 228 patients with unstable angina underwent PTCA. The primary success rate was 86.3 per cent in patients with stable angina (297 patients) and 87.7 per cent in patients with unstable angina (200 patients). The patients were recalled for systematic control coronary arteriography at 30, 60, 90, 120 or 150 days, and was obtained in 83.8 per cent of patients with stable angina and in 86 per cent of patients with unstable angina. The degree of stenosis before and the angiographic changes after PTCA and at control coronary arteriography were evaluated by a computer-assisted automatic contour detection system. The three criteria of restenosis were: 1) over 50 per cent loss of the benefit of PTCA, 2) residual post-PTCA stenosis increasing from less than 50 per cent to more than 50 per cent at control arteriography, 3) a decrease in the minimum intraluminal diameter of at least 0.72 mm with respect to the immediate post-PTCA result. A comparison between the two groups of patients showed that the average age was slightly greater in patients with unstable angina (56 +/- 9 years vs 58 +/- 9 years, p = 0.047). Apart from this difference, the two groups were comparable with regards to the average number of lesions dilated per patient, the date of control arteriography, the severity of the coronary artery disease and previous bypass surgery, angioplasty and infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108622 TI - The testicular effects of tumor necrosis factor. AB - Tumor necrosis factor (TNF) is a cytokine that mediates many of the metabolic responses after endotoxemia, septicemia, and tissue injury. The effect of TNF on testicular function was determined in a series of studies in which rhTNF (0, 2, and 4 X 10(5) units/kg/24 hours) was administered by continuous infusion to male Wistar rats maintained on total parenteral nutrition adequate for growing rats. Testicular weight and histology, and plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone levels were determined at 1, 3, and 6 days. Testicular weight decreased within 24 hours and this was associated with a fall in plasma testosterone and increased LH and FSH levels. These changes persisted for 6 days, indicating a loss of testosterone-mediated negative feedback on gonadotropin release. Histologic examination demonstrated significant damage to the germ cells in the adluminal compartment of the seminiferous epithelium; extensive exfoliation of spermatocytes and spermatids occurred at day six. However the primary spermatogonia in the basal compartment were relatively spared. Damage to the seminiferous epithelium at earlier times was noted in some tubules. The decrease in testosterone concentration and increase in gonadotropin levels suggest that TNF interferes with Leydig cell function. Germ cell damage may be a direct effect of TNF on these cells or may occur through secondary mechanisms involving Leydig or Sertoli cell dysfunction. PMID- 2108624 TI - [Comparative results of coronary angioplasty performed at the time of coronarography and at a later time]. AB - Between January 1986 and December 1988, 558 patients underwent percutaneous transluminal coronary angioplasty (PTCA) of whom 40 per cent were dilated at the time of diagnostic coronary arteriography. In order to assess the value of this therapeutic strategy we compared the results of 221 patients dilated at the time of diagnostic coronary arteriography (Group 1) with those of 337 patients who underwent deferred PTCA. In Group 1, the incidence of stable angina was lower (26.7% vs 46.3%, p less than 10-5), that of thrombolysed myocardial infarction was higher (24% vs 2.7%, p less than 10-9) and a higher proportion of patients had previously undergone PTCA (29.4% vs 3.2%, p less than 10-9). The proportion of patients with single vessel disease was higher in Group 1 (84.6% vs 74.7%, p less than 0.01) as was that of angioplasty of a single lesion (97.7% vs 88.1%, p less than 10-4). There were fewer dilations of the left circumflex artery in Group 1 (17.2% vs 27.3%, p less than 0.05) which was compensated by a higher number involving the right coronary artery (26.1% vs 15.5%, p less than 0.01). The immediate results were comparable in the two groups with 87.8 per cent primary successes, 3.6 per cent of myocardial infarcts and 1.3 per cent of coronary bypass operations with no fatalities in Group 1. These favorable results encourage the development of PTCA at the time of diagnostic coronary arteriography in the following indications: unstable angina, thrombolysed myocardial infarction and restenosis irrespective of the patient's symptomatology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108625 TI - [Initial and mid-term results of coronary angioplasty in early post-infarction unstable angina]. AB - The aim of this study was to assess the immediate efficacy and the medium-term risks and results of percutaneous transluminal coronary angioplasty (PTCA) in early post-infarction unstable angina. Thirty-six patients were included for a series of 248 consecutive PTCA procedures performed between December 1985 and January 1989. The average age was 56 years (range 35 to 84 years). The initial infarct was anterior (N = 16), inferior (N = 15), lateral (N = 5), without a Q wave (N = 22), transmural (N = 14) and treated by thrombolysis in 42 p. 100 of cases. The interval between initial infarction and PTCA was 16 +/- 3 days. A primary success was obtained in 33 cases (92%). One patient died of electromechanical dissociation at the beginning of the procedure. Two infarcts occurred due to acute coronary occlusions. None of the patients required emergency coronary bypass surgery. The specific risk of PTCA in early post infarction unstable angina is acute coronary occlusion. This complication was observed in 9 patients (25%) and it required immediate repeat PTCA, associated with thrombolytic therapy in four cases. Coronary occlusion was more common in patients with transmural infarcts than in those without Q-waves (43% vs 14%; p less than 0.01) and in patients treated initially by thrombolysis compared with those not treated by thrombolysis (40% vs 15%; p less than 0.05). No fatalities or reinfarctions occurred during follow-up (average 9 +/- 8 months, range 2 to 35 months). A good clinical result was maintained in 71 per cent of patients treated by PTCA alone. Seven repeat PTCA procedures and 3 coronary bypass operations were performed during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108626 TI - [Treatment of primary cardiogenic shock by coronary transluminal angioplasty during the acute phase of myocardial infarction]. AB - Cardiogenic shock is a very serious complication of acute myocardial infarction because of its prevalence (10-15% of cases) and the associated mortality of 80 to 90 per cent despite the availability of new inotropic drugs and intra-aortic balloon counterpulsation. The aim of this study was to show that revascularisation by percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction complicated by cardiogenic shock completely changes the prognosis. Between April 1985 and February 1988 emergency PTCA was carried out in 25 patients in cardiogenic shock defined as systolic hypotension (less than 80 mmHg) and clinical signs of peripheral or cerebral hypoperfusion. The patients were 21 men and 4 women with an average age of 62.7 +/- 6.7 years. The average delay before hospital admission was 122 mn (range 30 to 240 mn--40%--). External cardiac massage for ventricular arrhythmias or circulatory arrest was required in 56 per cent of cases and 20 per cent underwent balloon angioplasty during resuscitation. Five patients died in the catheter laboratory and 7 others during the hospital period. Thirteen patients (53%) survived and were discharged home. There have been no late deaths during the 24 month follow-up period; 46 per cent asymptomatic, 38 per cent in Class II and 16 per cent in Class III. Survival was better in the last 15 patients undergoing emergency angioplasty: 66 per cent compared with only 30 per cent in the first 10 patients in whom the decision to perform PTCA was then late, after failure of thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108627 TI - [Cardiac surgery in patients over 80 years of age. Experience of a series of 51 patients]. AB - Between January 1980 and June 1988, 51 patients over 80 years of age underwent open heart surgery at the La Pitie hospital (26 women and 25 men; average age 82 +/- 2 years, range 80-90 years). The cardiac pathology was calcific aortic stenosis (AS) in 40 cases, associated with coronary artery disease in 7 cases, mitral valve prolapse in 3 cases, coronary artery disease alone in 6 cases [complicated by a post-infarction ventricular septal defect (VSD) in one patient] or associated with aortic regurgitation in 1 case, and degeneration of an aortic bioprosthetic valve in 1 case. Forty patients (78%) were in Stage III or IV or the NYHA Classification. There was no other major pathology associated with the cardiac disease. Aortic valve replacement (AVR) was carried out in 42 patients, with a bioprosthetic valve in 38 patients. This procedure was associated with coronary bypass surgery in 7 cases and carotid artery surgery in 1 case. A mitral bioprosthesis was implanted in 2 patients and mitral valvuloplasty was carried out in 1 patient. An isolated myocardial revascularisation procedure was performed in 5 cases; the VSD was closed in 1 case. The hospital mortality was 17.6 per cent (9 patients). All deaths were of cardiac origin. Eleven patients had no postoperative complications at all. The 3 year survival rate of those who survived surgery was 71 per cent. Of the current 31 survivors, 29 are in Stage I or II of the NYHA Classification. These results suggest that surgery can be offered to octogenarians with invalidating cardiac disease alone carrying a poor short term prognosis. PMID- 2108628 TI - [Echography in surgical mitral insufficiency. Pathologic diagnosis and provision of the surgical procedure]. AB - The aim of this study was to determine the reliability of preoperative transthoracic and transesophageal echocardiography compared with the surgical findings in pure or dominant severe mitral regurgitation with respect to: the evaluation of the lesions, mechanism and etiology; the provision of the type of surgery (valve replacement or reconstruction); One hundred and fifty patients were divided into two groups: Group I (N = 120) in which preoperative assessment included transthoracic echo-Doppler coupled with color Doppler in the last 32 patients; Group II (N = 30) operated recently who underwent both transesophageal and transthoracic echo-Doppler examination. In Group I, the sensitivity of transthoracic echo in the evaluation of the etiological was 86% overall [100% in rheumatic valve disease (N = 28), 86% in degenerative or dystrophic valves (N = 72), 44% in endocarditis (N = 9), 87% in ischaemic dysfunction (N = 8)]. The echo evaluation of the mechanism of the regurgitation was also reliable with the exception of ruptured chordae in which direct visualisation of the rupture was only possible in 19 of the 64 cases (30%). The type of surgery predicted by echo was practiced in 87% of cases. PMID- 2108629 TI - [Changes in right ventricular ejection fraction in right coronary angioplasty]. AB - In order to analyse the response of the right ventricule (RV) to transient myocardial ischaemia, the RV ejection fraction was measured using a new rapid response thermodilution catheter in 15 patients (14 men and 1 woman: average age 58 +/- 7 years) referred for percutaneous transluminal coronary angioplasty of a dominant right coronary artery. Only patients with single vessel disease with a proximal stenosis of the right coronary without a visible collateral circulation who had no previous history of myocardial infarction were included. Right heart catheterisation was performed with a rapid-response thermodilution catheter which enabled measurement of heart rate, cardiac index, RV end-diastolic and end systolic volumes and RV ejection fraction. Angioplasty was carried out with the usual steerable balloon catheters. During balloon inflation, there was a slight increase in RV end-diastolic volume (from 78 +/- 11 ml/m2 to 85 +/- 13 ml/m2 at 60 seconds; p less than 0.01) and a large increase in RV end-systolic volume (from 29 +/- 8 ml/m2 to 35 +/- 8 ml/m2 at 30 seconds and 43 +/- 11 ml/m2 at 60 seconds, p less than 0.001) leading to a significant decrease in RV ejection fraction (from 62 +/- 8% to 56 +/- 6% at 30 seconds and 51 +/- 7% at 60 seconds; p less than 0.001). All parameters returned to basal values two minutes after the dilatation. Acute occlusion of the proximal segment of the right coronary artery is therefore associated with a marked change in right ventricular function which rapidly returns to normal after the coronary circulation is restored. PMID- 2108630 TI - [Biological monitoring of treatment with antivitamin K. Value of INR and definition of new therapeutic ranges. A study of 73 patients]. AB - The prothrombin time test (PT) is the most common method used for monitoring oral anticoagulant therapy. As a consequence of the variability in responsiveness of different thromboplastins, PT results obtained from patients on oral anticoagulant therapy may not be interchangeable between laboratories and as consequence could produce potential problems for anticoagulant control. The conversion of PT in INR (International Normalized Ratio) has been introduced recently to standardise the PT used for anticoagulant control. 127 determinations of prothrombin time and INR with 2 different thromboplastin reagents (Thromboplastin C Dade and Owren reagent) have been performed in 73 patients. This study confirm the usefulness of the INR (INR discrepancy in 10% of the cases) despite the imperfections concerning the choice of the control plasma and the need of a precise measurement of the ISI, International Sensitivity index. In parallel, changes in therapeutic ranges for anticoagulant therapy occurred, based on results of the international literature: less intense anticoagulant treatment (INR 2-3) is effective against recurrent venous thromboembolism with reduced bleeding. Different therapeutic ranges must be recommended for oral anticoagulant therapy according to the indication of the treatment. PMID- 2108631 TI - [Peripubertal longitudinal study by echocardiography of left heart development in a group of ice hockey players]. AB - The modalities of left ventricular (LV) adaptation (dilatation and/or hypertrophy) to exercise are not as well known in children as in adults. Therefore, the authors followed up 11 national ice hockey players, initially aged 10, following an eight hour per week training schedule for a period of 5 years. M mode echocardiographic studies were carried out each year during the training period to measure LV internal dimensions, wall thickness, myocardial mass and contractility (fractional shortening and systolic stress index). The evolution of these parameters was evaluated (Student's test) by two year peripubertal periods (10-12 years: 12-14 years) and compared in absolute values and in rate of growth with the standardised values indexed to body surface area reported by Henry. Between 10 and 12 years of age, the LV internal dimensions (a good indicator of LV volume in healthy children) increased significantly (p less than 0.05) and LV mass increased very significantly (p less than 0.01). The LV internal dimensions were normal at the outset and remained in the upper limits of normality reported by Henry with a normal rate of growth. Myocardial mass was normal at the age of 10 and its rate of growth was also normal. Between 12 and 14 years of age, the increase in LV internal dimensions was not statistically significant but myocardial mass increased very significantly (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108632 TI - [Mitral valve replacement in post-infarction rupture of the papillary muscle. Apropos of 13 cases surgically treated during the acute phase of infarction]. AB - Between 1983 and 1988, thirteen patients (12 men and 1 women, average age 63 years) were operated in the acute phase of myocardial infarction for papillary muscle rupture (PMR). The rupture involved the posterior papillary muscle in 12 cases. The average left ventricular ejection fraction was 47 +/- 9 per cent (range 34 to 63%). Pulmonary capillary pressures ranged from 76 to 41 mmHg (average 35 mmHg). Eleven patients presented with acute pulmonary oedema and 7 had cardiogenic shock. Coronary arteriography showed triple vessel disease in 3 cases, double vessel disease in 7 cases and single vessel disease in 3 cases. Surgery was carried out on average 2.7 days after the rupture and 10 days after the initial infarct. In addition to mitral valve replacement (N = 13), 11 patients underwent a myocardial revascularisation procedure. The operative mortality was 15 per cent (N = 2). Papillary muscle rupture in the acute phase of myocardial infarction causes cardiac failure which is related more to the mechanical abnormality than to an alteration of left ventricular function. Considering the operative mortality and the natural history of PMR treated medically, the authors recommend early surgery as the only management which can improve the precarious haemodynamic status of patients with this complication. PMID- 2108633 TI - [Iatrogenic coronary stenosis after angioplasty]. AB - Restenosis is the usual mechanism of recurrent myocardial ischaemia in the months following successful percutaneous transluminal coronary angioplasty (PTCA). Control coronary arteriography may occasionally show another cause: the constitution of a new stenosis near the dilated segment or in the left main coronary stem after angioplasty in a branch of this artery. The authors report 4 cases of patients who developed new coronary stenoses within a few weeks of PTCA, interpreted as traumatic complications of the initial procedure due to a lesion of the intima with a secondary fibrotic reaction and luminal narrowing. The guiding catheter was probably responsible for the trauma to the left main coronary stem whereas the tips of either the balloon catheter or the guide wire were thought to have been responsible for the endothelial effraction of the dilated vessels. PMID- 2108634 TI - [Comparison of the efficacy of verapamil and diltiazem in stable exercise angina. A double-blind and crossover study]. AB - Calcium channel blockers are now recommended for the treatment of stable angina but few studies have been carried out comparing the efficacy of verapamil and diltiazem in this indication. The short-term efficacy of these two drugs was compared in a double-blind crossover trial in 12 patients. The following protocol was used, 24 hour selection period followed by two crossover treatment periods versus double placebo. Exercise stress tests were performed 2 hours after the last dose at the end of each treatment period. Each patient underwent 3 stress tests: the first during the selection period whilst taking verapamil and diltiazem placebo (ET0), the second after the first treatment period at day 7 (ET1) and the third after the second treatment period at day 14 (ET2). A comparison of exercise capacity (ET0 to ET1 and ET2) showed improved effort tolerance and an increase in the ischaemic threshold with calcium blocker therapy. The duration of effort, the maximum sustained load, the rate-pressure product and the time to ST depression were all significantly increased. On the other hand, there were no significant changes in the percentage theoretical maximum heart rate attained, the heart rate at which ST depression occurred, the maximum ST depression and the incidence of angina. A comparison between ET1 and ET2 did not show any difference in the parameters of maximum effort or of the appearance of myocardial ischaemia. The comparison of exercise stress tests performed after treatment with verapamil and after diltiazem showed that the total duration of exercise, the maximum sustained load (in watts) and the rate pressure product were identical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108636 TI - [Dilated myocarditis and cardiomyopathies. The dysimmune hypothesis]. AB - A causal relationship between myocarditis and idiopathic dilated cardiomyopathy has long been suspected. Humoral and cellular immune mechanisms are most probably involved in the pathogenesis of these diseases. Human genotype may influence the outcome of lymphocytic myocarditis by means of the major histocompatibility complex. PMID- 2108635 TI - [So-called uremic heart diseases]. AB - The overall cardiovascular mortality in patients with chronic renal failure is about 30 per cent of which 10 per cent is attributed to myocardial infarction. This prevalence led some workers to propose a hypothesis of "accelerated atherosclerosis" due to the hyperlipidaemia observed in 30 to 70 per cent of patients. However, the concept of accelerated atherosclerosis, which was based essentially on clinical studies, has been questioned. Pericardial effusion is a common complication of chronic renal failure and has been reported in over 62 per cent of patients in echocardiographic studies. There are many causes and symptoms are often mild; systematic echocardiographic examination of patients with renal failure undergoing haemodialysis has shown 32 per cent of pericardial effusions to be asymptomatic. There are two potential complications: cardiac tamponade and, lesser frequently, constrictive pericarditis. Cardiac failure is a common cause of death in patients undergoing long-term dialysis. The myocardial histological appearances are those of fibrosis, the etiology of which is not fully understood although the dialysis membranes and hypotensive episodes occurring during haemodialysis have been thought to play a role. Left ventricular hypertrophy and fibrosis may give rise to ventricular arrhythmias which could explain some of the cases of sudden death observed in patients with renal failure and often wrongly attributed to ischemic heart disease. Another form of myocardial disease which is observed later is characterised by an alteration of systolic function with left ventricular dilatation and hypokinesia and increased end diastolic pressures without an increase in left ventricular wall thickness. Valvular heart disease may also result from renal failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108637 TI - [Floating left atrial thrombus in 2 cases of severe mitral stenosis]. AB - The authors report two operated cases of floating left atrial thrombus. Both patients had severe mitral stenosis, atrial fibrillation and dilatation of the left atrium. In the first case, the patient had no anticoagulant therapy; in the second case, the observance of anticoagulant therapy was irregular. Neither patient complained of syncope. The diagnosis was made in both cases by two dimensional echocardiography which, in addition to confirming the severe mitral stenosis, showed a round, free-floating intra-atrial mass, rebounding from wall to wall and repeatedly engaging itself into the mitral orifice. The risk of prolonged engagement of the thrombus in the mitral orifice, causing syncope or sudden death, justifies urgent surgery associating thrombectomy and treatment of mitral stenosis every time this problem is encountered. PMID- 2108638 TI - [Giant leiomyoma of the esophagus detected by echocardiography and corroborated by x-ray computed tomography and surgery]. AB - The authors report the case of a 44 year old man with a giant leiomyoma of the lower third of the esophagus. The patient presented with chest pain and the tumour was detected by echocardiography. The diagnosis was confirmed by computerised tomography and histological examination of the surgical specimen weighing 501.5 g. The surgeon performed a large esophago-gastric resection and reestablished the continuity of the digestive track by interposing a section of colon. A good result was obtained with a follow-up of 4 years. The authors underline the potential value of a simple barium swallow during cardiological assessment. PMID- 2108639 TI - [Refractory arterial hypoxemia and interatrial right-left shunt in myocardial infarction of the right ventricle]. AB - The authors report the case of a 63 year old woman who developed refractory arterial hypoxemia due to a right-to-left interatrial shunt through a patent foramen ovale during the acute phase of right ventricular infarction. The precarious haemodynamic condition of the patient contra-indicated surgical intervention and so the effects of the shunt were reduced by obstructing the atrial septal defect with the balloon of a Swan-Ganz catheter. The management of this type of shunt is discussed based on the degree of hypoxemia and the patient's haemodynamic status with reference to this particular case and a review of the literature. PMID- 2108640 TI - [Anistreplase in the treatment of myocardial infarction]. PMID- 2108641 TI - [Anistreplase. Pharmacology and biological data]. AB - Anistreplase is a second generation thrombolytic agent, an equimolecular streptokinase lys-plasminogen complex the active site of which is temporarily blocked by a p-anisoyle group. Acylation enables the drug to be administered as a bolus intravenous injection over 2 to 5 minutes, and it protects anistreplase against circulating inhibitors, hence a plasma elimination half-life of 90 minutes. Deacylation is slow and progressive (deacylation half-life: 105 minutes), and it begins as soon as the product is injected. It reduces the hypotensive effect of streptokinase, permits a prolonged action in the thrombus and limits the risk of reocclusion. Using lys-plasminogen increases the affinity of the drug for fibrin and potentiates its accumulation and retention in the thrombus. In vitro studies have shown that the affinity of anistreplase for fibrin is similar to that of t-PA. In doses used for myocardial infarction, anistreplase induces a pronounced fibrinogenolysis. The effectiveness of the drug has been demonstrated on numerous animal models and subsequently by clinical trials. PMID- 2108642 TI - [Coronary reperfusion by anistreplase (Eminase) used intravenously during the acute phase of myocardial infarction]. AB - Coronary recanalisation rate is one of the parameters utilized to evaluate the effectiveness of a thrombolytic agent. This parameter can only be measured when the occlusion and reopening of the coronary artery involved are demonstrated by angiography. Moreover, this type of study enables the kinetics of drug activity to be accurately determined. When injected intravenously in doses of 30 units less than four hours after the onset of chest pain and when studied by this method, Eminase produces recanalisation in more than 60 per 100 of the cases. The time elapsed between injection and action is 45 minutes on average. The risk of early reocclusion is low (about 5%). The recanalisation rate obtained with Eminase is similar to that obtained with intracoronary streptokinase. PMID- 2108643 TI - [Effects of anistreplase on coronary patency in acute myocardial infarction]. AB - Anistreplase or APSAC (anisoylated lys-plasminogen streptokinase activator complex) is a new, third generation thrombolytic agent with a long (90 minutes) elimination half-life, so that it can be administered by bolus intravenous injection over 2 to 5 minutes. In acute myocardial infarction anistreplase in doses of 30 units gives a coronary recanalisation rate of about 65 per cent and an early coronary patency rate of about 80 per cent. It is more effective than streptokinase on coronary patency, when given within 3 hours of onset of myocardial infarction. The time required for recanalisation to occur is short (25 to 45 minutes depending on the time elapsed before administration), and the early (24 hours) coronary reocclusion rate is low (about 5%). These results, together with the ease of administration of the drug, could make anistreplase the first choice thrombolytic agent in the treatment of recent myocardial infarction, notably in general hospitals and mobile intensive care units. PMID- 2108645 TI - [Study of survival using anistreplase (Eminase)]. AB - Thrombolytic therapy has been one of the most important advances in the field of cardiovascular medicine. Several agents are available and research is continuing to develop new effective thrombolytics with a rapid onset of action. The efficacy of thrombolytic therapy can be evaluated by a number of criteria such as the reperfusion time, the incidence of coronary recanalisation, left ventricular function, and survival. Survival is certainly the parameter of choice for assessing any thrombolytic protocol. The aim of this paper is therefore to review the results of survival studies with Eminase, one of the new thrombolytic agents used in the treatment of acute myocardial infarction. PMID- 2108644 TI - [Effect of thrombolytic agents on infarct size and left ventricle systolic function in myocardial infarction]. AB - The early intravenous administration of thrombolytic agents in the acute phase of myocardial infarction induces reperfusion of the artery responsible for the necrosis, thereby limiting the size of the infarct and preserving the left ventricular systolic function with consequent reduction of short- or long-term mortality. With the exception of urokinase, these effects have been demonstrated with all thrombolytic agents used so far, including streptokinase, plasminogen tissue activator and anistreplase. Owing to its special pharmacokinetic properties, the latest thrombolytic agent, formerly known as APSAC (anisoylated plasminogen streptokinase activator complex), provides a high arterial reperfusion rate with a low percentage of reocclusion. As a result, the mean size of the infarct is reduced by 31 per cent (36% in the case of anterior infarct), and the left ventricular systolic function is highly significantly preserved. PMID- 2108646 TI - [Pre-hospital thrombolysis]. AB - Too few myocardial infarctions are thrombolysed, and the thrombolytic agent is usually administered too late. This situation can conceivably be improved by educating both physicians and patients, by promoting thrombolysis in all hospitals and by performing thrombolysis before admission. We report here our experience of pre-hospital thrombolysis with Eminase in the Val-de-Marne department. This preliminary study is just a small stone added to the big heap of small series of thrombolysis at home published throughout the world. But while the feasibility of pre-admission thrombolysis has been well demonstrated, its effectiveness remains to be accurately determined. Two studies involving large groups of patients are currently in progress: one in Seattle with the left ventricular function as principal criterion of judgment, the other in Europe (The European Myocardial Infarction Project) with mortality as main criterion of judgment. We must wait for the results of these studies to know whether pre hospital thrombolysis will become the standard treatment of myocardial infarction and if so, to implement the relevant changes required in health structures. PMID- 2108647 TI - [Methods for evaluating thrombolytic drugs]. AB - There are two conceptually quite separate objectives to be attained in evaluating a new class of therapeutic agents: the establishment of benefit-risk relationships which allow assessment of their clinical utility; the evaluation of the underlying physiopathological concepts. These two distinct objectives overlap; the criteria of assessment of the benefit-risk studies are based on the physiopathological concepts. Similarly, the relationships observed after analysing the results of the benefit-risk studies increase our understanding of the physiopathology of a disease process. With respect to the use of thrombolytic drugs in the acute phase of myocardial infarction: --the usual criteria of evaluation of the benefits of treatment are coronary artery patency, left ventricular ejection fraction and patient mortality; the severity of blood clotting abnormalities and the frequency of haemorrhage are used to assess the risks; --the physiopathological reasoning behind this choice of criteria of assessment is the direct relationship between coronary artery patency, ejection fraction and mortality. Also, the severity of blood clotting abnormalities seems to be related to the frequency of haemorrhagic complications; We have reviewed these criteria of assessment of the benefit-risk ratio of thrombolysis in the acute stage of myocardial infarction. Our analysis indicates that mortality is the only indiscutable criterion of assessment and that the classical physiopathological concepts are not validated by the results of therapeutic trials. PMID- 2108648 TI - [Perfusion, filters and oligo-elements]. PMID- 2108649 TI - [Severe digestive manifestation of rheumatoid purpura. Retrospective study of 19 cases in children]. AB - Digestive and/or nutritional manifestations of Henoch-Schoenlein purpura (HSP) in childhood may be so severe as to require nutritional assistance. The study of 19 cases with this form of the disease allows to suggest a therapeutic protocol. When enteral nutrition cannot be used from the onset, parenteral nutrition is required. Associated steroid therapy may prove helpful for the regression of the digestive signs. The observed slowness of the weight catch-up, in spite of high protein-energy intakes, emphasizes the severity of catabolism in these severe forms of HSP. PMID- 2108650 TI - Crystalline light-chain deposition and amyloidosis in the thyroid gland and kidneys of a patient with myeloma. AB - A 48-year-old Japanese woman died of multiple myeloma (lambda light-chain type) with chronic renal failure. Histological examination revealed deposition of a homogeneous substance and crystals in the kidneys and thyroid gland. The homogeneous substance was stained with Congo red after permanganate treatment but did not stain with antibody to amyloid A protein, and it was recognized as AL type amyloid. Crystals were not stained with Congo red, but crystals were stained with antibody to the lambda light chain. Since AL-type amyloid is considered to be derived from a myeloma light chain, the present case showed two different types of deposition, both of which were derived from the same myeloma protein. PMID- 2108651 TI - Enterococcal sepsis and lung microvascular injury in sheep. AB - In a common bile duct contamination model, we studied the effect of Streptococcus faecalis compared with Escherichia coli in sheep with chronic lymph fistulas to investigate the role of enterococcus in acute lung injury and acute sepsis. Early pulmonary hypertension in the E coli group was not expressed in the S faecalis group, probably due to a failure of S faecalis to illicit a thromboxane A2 response. In the late period, E coli was associated with significantly greater lung microvascular damage compared with S faecalis. The lack of difference between groups with respect to complement activation suggests the action of chemotactic factors, in addition to complement, mediating granulocyte aggregation, and neutropenia. In this model, S faecalis demonstrated limited pathogenicity as expressed in lung microvascular injury compared with E coli. PMID- 2108652 TI - Interferon gamma and tumor necrosis factor alpha. Use in gram-negative infection after shock. AB - Shock increases the propensity to develop infection after injury or operation. This study evaluated the effect of cefoxitin, interferon gamma (INF-gamma), and tumor necrosis factor alpha (TNF-alpha) on the development of a polymicrobial soft-tissue infection. After sham operation or hemorrhagic shock and resuscitation, Sprague-Dawley rats were inoculated with 1 x 10(8) Escherichia coli and 1 x 10(9) Bacteroides fragilis in a 5% fecal suspension. Animals received either no treatment, cefoxitin, recombinant rat INF-gamma, recombinant human TNF-alpha, or cefoxitin/cytokine combinations. Cefoxitin reduced abscess size by 57% in animals without shock but only by 26% after shock. Although neither INF-gamma nor TNF-alpha alone had a salutary effect when given with cefoxitin in animals after shock, INF-gamma and TNF-alpha reduced abscess size by 50% and 55%, respectively. These results suggest that INF-gamma and TNF-alpha may be useful to reduce the severity of mixed gram-negative infections after shock with bacterial contamination. PMID- 2108653 TI - Liver biochemical and histological changes with graded amounts of total parenteral nutrition. AB - We sought to determine whether an excess in energy intake as total parenteral nutrition would result in liver biochemical and histological changes in the presence of a functional gastrointestinal tract. Three groups of rats were given amounts of total parenteral nutrition that provided either 25% (total parenteral nutrition-25), 100% (total parenteral nutrition-100), or 200% (total parenteral nutrition-200) of a rat's energy requirements. Rat chow and water were available ad libitum. Food intake decreased in proportion to the amount of total parenteral nutrition infused; it ceased with total parenteral nutrition-200. Liver glycogen and triglyceride concentrations were higher with high energy intake (total parenteral nutrition-100 and total parenteral nutrition-200), while total liver nitrogen concentrations remained unchanged. No cholestasis, inflammation, or fibrosis was seen histologically. Fatty vacuoles were increased with total parenteral nutrition (more so with total parenteral nutrition-200) but a prompt return to normal liver features was observed after cessation of total parenteral nutrition and the resumption of normal food intake. PMID- 2108654 TI - Vagotomy effect on gastric prostaglandins. Primarily neural or secondary to hypoacidity? AB - Prostaglandins have been implicated in gastric mucosal cytoprotection. Vagotomy results in both cytoprotection and increased mucosal prostaglandin concentrations. However, the mechanism by which vagotomy affects prostaglandin generation remains unknown. In this study we compared vagotomy with long-term acid suppression using anticholinergic (atropine sulfate) or histamine2-receptor antagonism (cimetidine) and assessed mucosal injury and prostaglandin generation during graded stress. Vagotomy correlated with decreases in injury only in severe stress, while both atropine and cimetidine decreased injury also during moderate stress. Prostaglandin generation decreased in all groups during severe stress. Compared with sham operation, vagotomy, atropine, and cimetidine were all associated with increased mucosal prostaglandin generation in all stress periods. During severe stress, both atropine and cimetidine also evidenced higher prostaglandin generation than did vagotomy. These results suggest that vagotomy primarily decreases acid secretion, which then secondarily results in increased mucosal generation. PMID- 2108655 TI - Of mice--and rats, dogs, rabbits, cats, and monkeys--and men. PMID- 2108656 TI - Microsporidial keratoconjunctivitis in acquired immunodeficiency syndrome. AB - We describe three patients with acquired immunodeficiency syndrome who presented with a bilateral coarse superficial epithelial keratitis due to infection with the protozoal parasite Microspora, Encephalitozoon cuniculi. Despite the extent of the corneal surface disease, conjunctival inflammation was minimal. Visual acuity ranged from 20/20 to 20/200. In one patient, the keratitis was complicated by the development of a surface defect with secondary Pseudomonas species infection. All patients had a history of exposure to household pets. Standard cultures were negative. Diagnosis was established in two of the three cases based on characteristic appearance of the protozoan in conjunctival scrapings. Electron microscopy of a conjunctival biopsy specimen in one patient confirmed the species. No recognized effective treatment is available for this infection. PMID- 2108657 TI - Dimensional change of impressions on sterilization. AB - The volume of impressions, before and after disinfection in a gluteraldehyde solution for longer than ten hours (that is, sterilization), was measured indirectly from dies produced from the impressions. Three elastomeric impression materials were used in both acrylic resin and poly-vinyl-chloride 'trays' to form the impressions. One impression material appeared to be practically superior to the others with respect to variability of volume. The effect of tray material on change in volume (calculated as after disinfection minus before disinfection) was significant for one impression material; acrylic trays produced the greatest effect. The change in volume was significant for two impression materials; acrylic trays were associated with greater increase in volume. It was concluded that if impressions are to be sterilized, a tray material having minimal potential to absorb disinfectant should be used. PMID- 2108658 TI - Keeping the pulp alive: the pharmacology and toxicology of agents applied to dentine. AB - Materials applied to teeth release chemicals which may diffuse through dentine to either harm or help the dental pulp. Chemical threats are minimized by material choice or by using relatively impermeable lining or base materials which are themselves of low chemical toxicity. The most probable long-term threat to the pulp in the restored tooth is bacterial, through leakage around restorations. This may be prevented by the use of treatment sequences designed to develop an effective seal. Pulpal inflammation is treated primarily by removal of the irritant cause; inflammation may also be suppressed in the very short term by corticosteroids, and its resolution aided in the longer term by zinc oxide eugenol preparations. PMID- 2108659 TI - Antibiotics and endodontics. AB - Antibiotics can be used as an adjunct to endodontic treatment in a number of ways -locally, systemically and prophylactically. The local or intra-canal use of antibiotics in the form of medicaments is common. However, the commercially available agents for this purpose may not be the ideal mixtures. Systemic antibiotics should be restricted to patients who have local signs of infection, malaise and elevated body temperature. Prophylactic use of antibiotics has been recommended for patients 'at risk' of infective endocarditis, in some pre surgical situations and following avulsion and replantation of teeth. The tendency towards indiscriminate antibiotic use should be discouraged. The use of broad spectrum drugs should be restricted so that these medications remain effective in serious situations. PMID- 2108660 TI - Arbovirus infection in humans in NSW: seroprevalence and pathogenicity of certain Australian bunyaviruses. AB - A sero epidemiological study was carried out on human sera from all regions of New South Wales for the presence of antibodies to nine bunyaviruses viz Aino, Akabane, Belmont, Gan Gan, Kowanyama, mapputta, Peaton, Tinaroo, Trubanaman and the orbivirus Corriparta. Neutralising antibodies were found in titres up to 1280 to Gan Gan and to 640 to Trubanaman viruses, prevalences 4.7% and 1.4% respectively. Neutralisation titres up to 40 were found to Belmont, Aino, Peaton and Corriparta viruses but the significance of these is uncertain since they may represent either non-specific inhibitors or cross reacting antibodies to related but currently unknown viruses. No antibodies were found to Akabane, Kowanyama, Mapputta or Tinaroo viruses in New South Wales sera. Gan Gan virus appeared to be pathogenic for man being associated with an acute epidemic polyarthritic like illness. Trubanaman virus is suspected of being pathogenic. This is the first report of the pathogenicity of these Australian bunyaviruses. PMID- 2108661 TI - Chronic non-A, non-B hepatitis: lack of correlation between biochemical and morphological activity, and effects of immunosuppressive therapy on disease progression. AB - A study was made of 52 patients considered to probably have chronic non-A, non-B hepatitis who were seen during an eight-year period at Westmead Hospital, Sydney. The patients were followed for a median of 28 months to assess the natural history of the disease and, in a small number of patients, the effect of immunosuppressive therapy on disease progression was examined. In 94% of cases, infection appeared to have been acquired by a parenteral route; the remainder were sporadic infections. Fifty-six per cent of the patients had mild constitutional symptoms and the remainder were asymptomatic. Similarly, 54% of patients had no signs of chronic liver disease and none exhibited signs of hepatic decompensation. Liver biopsies were performed in 42 patients; chronic active hepatitis with or without cirrhosis was present in 90%. However, neither the presence of symptoms nor the degree of biochemical abnormality were predictive of disease severity as determined histologically. Among eight patients treated with corticosteroids (with or without azathioprine), six underwent follow up liver biopsy. Quantitative analysis of inflammatory and fibrotic changes indicated significant (p less than 0.01) progression of histological severity during a median 33 months (range 7-98 months) between biopsies with cirrhosis developing in four instances. In contrast, among the seven untreated patients rebiopsied after a median of 16.0 months (range 11-37 months) there was no overall change in histological severity and only one patient developed cirrhosis. it is concluded that histological assessment is required in all patients suspected of having chronic non-A, non-B hepatitis as other means of assessment are unreliable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108662 TI - Hatching eggs sanitized with chlorine dioxide foam: egg hatchability and bactericidal properties. AB - The efficacy of chlorine dioxide (ClO2) as an alternative sanitizing agent for hatching eggs was investigated because of the health concerns about formaldehyde fumigation. Hatchability of chicken eggs was reduced when the eggs were dipped in the ClO2 solutions for more than 5 minutes or in concentrations greater than 100 ppm Cl. However, treating hatching eggs with a ClO2 foam or fumigating with formaldehyde had no adverse effect on hatchability compared with untreated control eggs. Sanitizing soiled duck eggs with ClO2 foam improved hatchability by more than 10% and hatch by more than 6% compared with untreated eggs (P less than 0.05). A novel method for assessing bactericidal potential of egg-sanitizing agents was developed. Using this technique, both chlorine dioxide foam and formaldehyde fumigation reduced the number of egg-contaminant bacteria inoculated on sterile chicken eggs compared with the number of bacteria on untreated eggs (P less than 0.05). These findings suggest that sanitizing hatching eggs with ClO2 foam may be a viable alternative to fumigating with formaldehyde. PMID- 2108664 TI - Chromosome structure at interfaces between major chromatin types: alpha- and beta heterochromatin. AB - The chromocenter of Drosophila polytene chromosomes, which consists of two major chromatin types, has long been a troublesome region in molecular terms. The recent microcloning of part of this region, the isolation of a monoclonal antibody to a beta-heterochromatin binding protein, and new in situ studies now shed a little more light on this chromosomal region. PMID- 2108663 TI - Identification of the chicken anemia agent, reproduction of the disease, and serological survey in the United States. AB - An agent with antigenic, physicochemical, and pathological characteristics of chicken anemia agent (CAA) was isolated from broiler chickens and was designated chicken infectious anemia (CIA)-1. CIA-1 was resistant to chloroform treatment and passed through 50-nm-diameter-pore membranes. When inoculated in embryonally bursectomized and/or intact chickens, CIA-1 produced signs and lesions characteristic of CIA: low hematocrit values, pale bone marrow, thymic and bursal atrophy, and enlarged liver. Microscopic lesions were a reflection of macroscopic observations. When injected into 4-week-old chickens CIA-1 induced antibodies against the Cux-1 CAA isolate. In CsCl, CIA-1 had a density of 1.36 g/ml. Antibodies against CAA were found in breeder and commercial chicken flocks from Arkansas, Connecticut, Georgia, Kansas, Maine, Michigan, New York, and Pennsylvania. The age of these flocks ranged from 10 to 78 weeks. PMID- 2108665 TI - Transcriptional regulation of the Drosophila segmentation gene fushi tarazu (ftz) AB - ftz is one of the 'pair rule' segmentation genes of Drosophila melanogaster, and is an important component of the segmentation process in the fruit fly. We discuss the transcriptional mechanism which causes ftz to be expressed in a seven stripe pattern during embryogenesis. PMID- 2108666 TI - Discovery of the nucleolar targeting signal. AB - The discovery of the signal peptides that direct proteins to localize at the nucleolus is described here. The nucleolar targeting signal termed the NOS consists of clustered basic amino acids organized such that a portion also functions as the nuclear transporting signal. Although a NOS has been identified within the regulatory genes of human retroviruses, HTLV-I and HIV-I, signals of similar function in cellular proteins--such as heat shock proteins--may be induced through the configurational change of protein structure by heat or stress. PMID- 2108667 TI - Identification of germination gene of Bacillus megaterium. AB - Glucose, KNO3, proline and leucine initiate the spore germination of B. megaterium ATCC 12872, but not of B. megaterium ATCC 19213. In order to isolate the gene concerning germination of B. megaterium ATCC 12872, we constructed its gene library in plasmid vector, and introduced into B. megaterium ATCC 19213. We obtained a transformant whose spores differed from those of the wild type strain with respect to germinability. Spores of this transformant could be germinated by glucose, proline or leucine. The recombinant plasmid prepared from this transformant was found to carry 2 kilobase pairs fragment of B. megaterium ATCC 12872 DNA. This fragment may contain the gene encoding the protein which plays an important role in germination. PMID- 2108668 TI - Leukotrienes are active in the rosette inhibition assay mimicking the action of 'early pregnancy factor'. AB - Lipoxygenase metabolites have been found to be active in the rosette inhibition assay by inducing increased rosette inhibition titres. Leukotrienes B4, C4, D4 and E4 were identified as possessing this activity. The cycloxygenase products, prostaglandins E2, D2 and F2 alpha had no such activity; however, prostaglandin E2 and to a lesser degree prostaglandin D2 could counteract the activity of the leukotrienes in this assay. The identified leukotrienes are the first characterised molecules known to display activity in the assay. In this respect they mimic the action of early pregnancy serum, an action ascribed to a so called 'early pregnancy factor'. PMID- 2108669 TI - Electrospray ionization mass spectrometric peptide mapping: a rapid, sensitive technique for protein structure analysis. AB - Electrospray ionization mass spectrometric peptide mapping is demonstrated to be a useful new technique for protein structure analysis. The procedure involves the digestion of the protein with trypsin and subsequent analysis of the total unfractionated digest by electrospray ionization mass spectrometry. The utility of the technique for investigating protein structure is illustrated by a peptide mapping analysis of human apolipoprotein AI (Mr = 28 kDa). The technique is rapid, sensitive, and requires no prior separation of the peptides. The discrimination effects observed in other mass spectrometric methods are less important in the present procedure. PMID- 2108670 TI - Characterization of a putative promoter region of the human poly(ADP-ribose) polymerase gene: structural similarity to that of the DNA polymerase beta gene. AB - The 5'-flanking region of the human poly(ADP-ribose) polymerase gene was isolated and characterized. The nucleotide sequence of a part of the poly(ADP-ribose) polymerase gene completely matched that of the cDNA. The transcriptional initiation sites (cap sites) of this gene, located about 166-bp upstream from the translational initiation site, were identified by S1 mapping analysis. Neither CAAT box nor TATA box was found within 500-bp upstream from the cap sites of poly(ADP-ribose) polymerase gene. The 200-bp immediately upstream of the cap site had a high G+C content (76.5%) and contained double repeats of the sequence CCGCCC, putative Sp1 binding sites, and a palindromic structure. The 5'-flanking region of poly(ADP-ribose) polymerase gene also showed promoter activity in chloramphenicol acetyltransferase assay and structural similarity to that of DNA polymerase beta gene. PMID- 2108671 TI - Expression, glycosylation, and intracellular distribution of human beta galactosidase in recombinant baculovirus-infected Spodoptera frugiperda cells. AB - A full-length cDNA encoding human acid beta-galactosidase was inserted into the baculovirus genome under transcriptional regulation of the viral polyhedrin gene promoter. The Spodoptera frugiperda cells infected with the recombinant virus expressed the beta-galactosidase activity 300-fold higher than human fibroblasts. Immunoblot analysis revealed an 82-kDa protein band, which was modified in molecular size by deglycosylating enzymes; an 80-kDa band appeared after N glycanase digestion, and two bands (80-kDa and 81-kDa) appeared after endoglycosidase H digestion. This result suggested that the enzyme molecule was glycosylated, partly with high-mannose type oligosaccharides. The intracellular distribution of the enzyme observed by indirect immunofluorescence staining was perinuclear or diffusely cytoplasmic, and not characteristic of lysosomes; the enzyme was secreted to the culture medium in large quantities, and not translocated to lysosomes. Possible application of this expression system to the studies of the structure and function of normal and mutant human beta galactosidases was discussed. PMID- 2108672 TI - The interaction of adenosine diphosphoribosyl transferase (ADPRT) with a cruciform DNA. AB - Adenosine Diphosphoribosyl Transferase is a eucaryotic nuclear protein that catalyses the transfer of ADP-ribose moiety of NAD+ to itself and other cellular proteins. DNA is required for this post-translational modification process. We present novel evidence that Adenosine Diphosphoribosyl Transferase interacts with the base of plasmid pUC7 cruciform. We speculate that, unlike a sequence-specific DNA binding protein, the transferase may recognize an unusual DNA conformation. PMID- 2108673 TI - Specific, high-affinity binding sites for human luteinizing hormone (hLH) and human chorionic gonadotrophin (hCG) in Candida species. AB - The presence of specific binding sites for [125I]-labelled hLH and hCG is described in Candida species. Binding was present in three strains of Candida albicans, and in Candida tropicalis, and was greatest in microsomes, though binding was also present in cytosol fractions. hLH and hCG mutually competed for these binding sites. Other hormones did not bind and did not compete for hLH binding sites. Scatchard plots showed two classes of binding sites, one with high affinity, low capacity and the other with lower affinity, high capacity binding in both microsomes and cytosol. This is the first report of specific binding sites for mammalian peptide hormones in a yeast. PMID- 2108674 TI - Involvement of protein kinase C in the regulation of assembly-disassembly of neurofilaments in vitro. AB - Protein kinase C phosphorylated the major mammalian neurofilament protein (NF-L) with approximately 3 mol phosphate per mol protein. The phosphorylated NF-L no longer formed the filaments. Sequential analysis of the tryptic phosphopeptides, together with the known primary sequence, revealed that Ser-12, Ser-27, Ser-33 and Ser-51 were phosphorylated by protein kinase C. These findings contribute toward elucidation of mechanisms regulating the functions of neurofilaments. PMID- 2108676 TI - Identification of high and low (GTP-sensitive) affinity [3H]glibenclamide binding sites in cardiac ventricular membranes. AB - Glibenclamide is an antagonist of the ATP-modulated K+ channel in cardiac tissue. This study showed glibenclamide to bind to high (0.2 nM) and low (40 nM) affinity binding sites in canine ventricular membranes. Gpp [NH]p significantly altered the binding characteristics of the low affinity site, while those of the high affinity site were unchanged. This indicates independence of the two sites and suggests the low affinity site may be coupled to a G-binding protein. Although we have identified two [3H]glibenclamide binding sites, the importance of these sites to the cardiac effects of glibenclamide remains to be determined. PMID- 2108675 TI - Pertussis toxin inhibits EGF-, phorbol ester- and insulin-stimulated DNA synthesis in BALB/c3T3 cells: evidence for post-receptor activation of Gi alpha. AB - The contribution of the GTP-binding protein, Gi, to EGF, phorbol dibutyrate (PdBu)-, and insulin-stimulated DNA synthesis was examined in BALB/c3T3 cells. Pertussis toxin inhibited DNA synthesis by each agonist, particularly at suboptimal agonist concentrations, but the inhibition could be partially overcome with higher agonist concentrations and combinations of these agonists. This suggested that (1) some, but not all, of the mitogenic signals for all three agonists were transduced by Gi (2) Gi may be activated by post-receptor mechanisms involving protein kinase C. Gi alpha-specific antibodies and ADP ribosylation by pertussis toxin using 32P-NAD each labelled a single protein band, representing one or more species of Gi alpha. Pertussis toxin treatment increased the synthesis of Gi alpha. These results are discussed in relation to possible direct effects of Gi alpha on nuclear control during division. PMID- 2108677 TI - Nuclear pp64 is phosphorylated in both serine/threonine and tyrosine through complex pathways regulated by 12-O-tetradecanoylphorbol-13-acetate and platelet derived growth factor. AB - Platelet-derived growth factor (PDGF) induces the time and dose dependent serine/threonine phosphorylation of pp64, a nuclear protein in normal rat kidney (NRK) cells. pp64 is phosphorylated additionally on tyrosine in SSV-transformed NRK cells. To further characterize the regulation of phosphorylation of pp64, other mitogens and inhibitors were studied. 12-O-tetradecanoylphorbol-13-acetate (TPA) but not epidermal growth factor (EGF) or insulin induced the phosphorylation of nuclear pp64. Addition of the inhibitor H7 to TPA-treated NRK cells resulted in a striking further increase in phosphorylation of pp64 and, to a lesser extent, in NRK cells treated with PDGF and H7. When cells were treated with PDGF and H7, pp64 was recognized by anti-phosphotyrosine antisera. The increased phosphorylation induced by H7 was inhibited when forskolin was included. This loss of phosphorylation in pp64 with forskolin treatment paralleled a loss of immunoreactivity of pp64 to anti-phosphosphotyrosine. Complex and independent pathways thus appear to signal the growth factor dependent nuclear phosphorylation of pp64, involving phosphorylations both on serine/threonine and on tyrosine. PMID- 2108678 TI - Rapid Ca2+ refilling system of intracellular store(s) in human vascular endothelial cells. AB - Using a fura-2 method, cytosolic Ca2+ concentration [( Ca2+]i) was measured in endothelial cell monolayers from human umbilical vein. In the presence of 1.5 mM Ca2+, bradykinin (BK) induced a rapid (within 15 sec) and dose-dependent (10(-8) 10(-6) M) increase in [Ca2+]i, consisting of an initial peak and a subsequent sustained phase. The pretreatment with 3 mM EGTA for 1 min caused a significant reduction in [Ca2+]i levels both of the basal (p less than 0.05) and BK stimulated initial peak (p less than 0.001). However, the BK-stimulated initial peak was retained in magnitude for at least 5 min under the treatment with EGTA. In contrast, the sustained phase was completely abolished by EGTA treatment. The BK-stimulated Ca2+ transient, once having been completely inhibited by ionomycin (10(-6) M) in the presence of EGTA, was rapidly (within 2 min) recovered to the untreated level by replacing it with fresh medium containing 1.5 mM Ca2+. The present results indicated that BK mobilized Ca2+ from both intracellular and extracellular space(s) and suggest the presence of an extracellular Ca2(+) dependent rapid refilling system of intracellular Ca2+ store(s) in human vascular endothelial cells. PMID- 2108679 TI - Structure and expression of cysX, the second gene in the Escherichia coli K-12 cysE locus. AB - Protein products of the cysE region at 81 min on the chromosome of Escherichia coli K-12 (1) were analyzed by the maxicell method. Two kinds of polypeptides of molecular weight 33 K and 16 K were the products. The open reading frame (ORF) of the 33 K polypeptide consisted of 273 amino acids (Mr = 29,261). On the other hand, the 16 K ORF was overlapped by the opposite 33 K ORF and specified an extremely basic protein of 130 amino acids (Mr = 15,233). The gene coding for the 16 K polypeptide was named cysX. The expression of cysE and cysX in vivo was confirmed further by constructions of the cysE'-'lacZ and cysX'-'lacZ hybrid genes. PMID- 2108680 TI - Inhibition of gastric pepsin secretion by peripherally or centrally injected interleukin-1 in rats. AB - The present study was carried out to investigate the effects of Interleukin-1 (IL 1) on gastric pepsin secretion in conscious pylorus-ligated rats. The intraperitoneal (ip) injection of IL-1 resulted in a dose-related inhibition of gastric pepsin output. The intracerebroventricular (icv) injection of IL-1 similarly reduced pepsin secretion at 100 times smaller doses than ip IL-1, suggesting that this inhibitory action of IL-1 is mediated by the central nervous system (CNS). In addition, it was found that the antisecretory action of IL-1, both peripherally and centrally administered, lasted throughout the periods observed (2 hr through 8 hr after injection). These results strongly indicate that IL-1 is involved in the CNS regulation of gastric secretion, especially under certain pathophysiological conditions which activate the immune system to release various cytokines including IL-1. PMID- 2108681 TI - NADPH cytochrome P-450 reductase in rat, mouse and human brain. AB - NADPH cytochrome P-450 reductase (P-450 reductase), an essential component of the cytochrome P-450 mono-oxygenase system, has been estimated in rat and mouse brain, and seven human brains obtained at autopsy. The ratio of cytochrome P-450 to P-450 reductase is lower in the rat and mouse brains (2.5-4.0) as compared to the respective livers (10.0-11.0). The rat and mouse brain P-450 reductase were immunologically similar to the rat liver P-450 reductase as examined by immunochemical inhibition, Ouchterlony double diffusion and immunoblot. The antisera to rat liver P-450 reductase inhibited rat brain aminopyrine N demethylase activity to the same extent as NADPH cytochrome c reductase, suggesting that the level of P-450 reductase controls the rate of this cytochrome P-450 mediated activity. The human brain NADPH cytochrome c reductase exhibited regional variation, maximal activity being observed in the brain stem region. Immunochemical inhibition and immunoblot studies revealed immunological cross reactivity between rat liver reductase and human brain medulla, while none was observed in cortex or cerebellum. Immunocytochemical studies on human brain medulla using antisera to rat liver P-450 reductase indicated localization of the P-450 reductase in neuronal cell body. PMID- 2108682 TI - Mechanism of growth inhibition of melanoma cells by 4-S-cysteaminylphenol and its analogues. AB - Our previous studies have shown that 4-S-cysteaminylphenol (4-S-CAP) causes a significant inhibition of in vivo melanoma growth and a marked depigmentation of black skin and hair follicles. These studies have suggested a role of tyrosinase in the manifestation of these in vivo effects. In this study 4-S-CAP and its analogues were examined for their effects on the growth of human melanoma cells in vitro. 4-S-CAP and 4-S-HomoCAP exhibited strong cytotoxicity with effects much greater than those of alpha-methyl-4-S-CAP and N,N-dimethyl-4-S-CAP. The cytotoxicity of the former two amines was completely prevented by semicarbazide, an inhibitor of plasma monoamine oxidase, while that of the latter two was not prevented by semicarbazide, catalase, and phenylthiourea, a tyrosinase inhibitor. In culture medium 4-S-CAP was rapidly converted by the action of monoamine oxidase present in fetal bovine serum to the aldehyde which was then metabolized to the alcohol and the carboxylic acid when cells were present. alpha-Methyl-4-S CAP was found to exert higher cytotoxicity to cells with higher tyrosinase activity and melanin content. These results suggest that the in vitro cytotoxicity of 4-S-CAP and 4-S-HomoCAP is mediated through conversion to the aldehydes while that of alpha-methyl-4-S-CAP appears to be dependent on tyrosinase activity to some extent. PMID- 2108683 TI - Ascorbic acid deficiency and hepatic UDP-glucuronyl transferase. Qualitative and quantitative differences. AB - The effect of dietary ascorbate on hepatic UDP glucuronyltransferase (UDPGT) appears to be selective in that only certain isozymes of UDPGT are jeopardized. In this study, ascorbic acid deficiency produced a 68% reduction in the specific activity of hepatic UDPGT towards p-nitrophenol. Earlier studies showed a reduction in UDPGT activity towards p-aminophenol in ascorbate-deficient guinea pigs, whereas bilirubin and acetaminophen glucuronidation were unaffected. Kinetic studies suggest that p-aminophenol and p-nitrophenol are metabolized by a single isozyme in that p-nitrophenol was found to be a competitive inhibitor of p aminophenol glucuronidation. Both qualitative and quantitative studies on partially purified UDPGT from ascorbate-deficient and ascorbate-supplemented guinea pigs were carried out to investigate the biochemical role of the vitamin. Qualitative differences were observed in UDPGT from ascorbate-deficient animals and included an increased lability to: thermal inactivation; storage at 4 degrees; and purification with UDP-glucuronic acid agarose column chromatography. Furthermore, an analysis of the microsomal membrane showed a 14% increase in membrane fluidity in ascorbate deficiency. Ascorbic acid added in vitro could not reverse the increase in fluidity observed in ascorbate-deficient microsomal membranes; however, ascorbylpalmitate, a more lipophilic form of the vitamin, was effective. Palmitic acid had no effect on membrane fluidity in microsomes from either the ascorbate-supplemented or ascorbate-deficient animals. This increase in membrane fluidity could not be explained by differences in cholesterol, total phospholipid, or phosphatidylcholine content of hepatic microsomes. Furthermore, a quantitative reduction in UDPGT partially purified from ascorbate-deficient guinea pigs was indicated by a marked reduction in protein banding at 55,000 daltons when compared to UDPGT partially purified from ascorbate-supplemented animals. PMID- 2108684 TI - Inhibition of prostacyclin formation by cyclosporin is not due to reduced availability of arachidonic acid in membrane phospholipids of cultured human endothelial cells. AB - Our studies have shown that CS inhibits PGI2 production in HUVEC, that this inhibition is not overcome when exogenous AA is supplied, that the inhibitory action of CS is proximal to PGI2 synthetase and finally that there is abundant free AA available in membrane phospholipids of CS treated HUVEC [4,5]. In conclusion, CS does not appear to inhibit PGI2 synthesis by reducing the availability of free AA in the endothelial cell membrane. Although CS appears to inhibit cyclo-oxygenase, we can not exclude an additional effect on acyltransferase. PMID- 2108685 TI - Effects of ursodeoxycholate on maximal biliary secretion of bilirubin in the rat. AB - The effect of sodium ursodeoxycholate (0.5 and 1.0 mumol/min/100 g) on the maximal biliary secretion (Tm) of bilirubin and on the concentration of bilirubin in liver and plasma at the end of a bilirubin load was studied in Wistar rats. Administration of ursodeoxycholate at 0.5 mumol/min/100 g caused a 0.8-fold increase in bile flow and a significant increase in the bilirubin Tm (+24%). This was associated with a significant reduction of liver and plasma bilirubin concentrations (-16% and -17%, respectively). Bilirubin UDP glucuronosyltransferase activity was not significantly enhanced. There was a significant increase in the biliary excretion of bilirubin conjugates (+30%) and in the diconjugates/monoconjugates ratio in bile (+31%). When ursodeoxycholate was given at 1.0 mumol/min/100 g, it produced a 1.7-fold increase in bile flow, but the bilirubin Tm was significantly reduced (-21%). Liver bilirubin concentrations were decreased (-20%) and there was a significant enhancement in total pigment concentration in plasma (+19%). Both the excretion of unconjugated bilirubin and that of bilirubin conjugates were significantly reduced (-60% and 18%, respectively). There was a significant decrease in the bilirubin-UDP glucuronosyltransferase activity and the diconjugates/monoconjugates ratio in bile (-27% and -27%, respectively). These results indicate that ursodeoxycholate is able to increase maximal bilirubin secretion only when administered at low doses and that infusion at higher rates can significantly interfere with different steps in the hepatobiliary transport of the pigment. PMID- 2108686 TI - Heterogeneity of rat plasma albumin and drug binding. AB - Rat plasma albumin fractionated by Sephadex G-75 (superfine) gel filtration from freshly prepared rat plasma was further separated into three major fractions by chromatofocusing column chromatography. All the fractionated albumins had high binding affinity for the fluorescent probe 8-anilino-1-naphthalenesulfonic acid, as the model compound for acidic drugs, and were found to be immunologically identical. PMID- 2108687 TI - Depressant effect of very low levels of aflatoxin B1 on mouse glyoxylase-I activity and methylglyoxal disposal. PMID- 2108690 TI - Preemployment physical examinations. Report of a pilot program. AB - 1. Due to costly workers' compensation claims, the state of Arizona instituted a preemployment physical exam program for state jobs. 2. Thorough job analyses are conducted for working conditions and physical ability requirements on high risk jobs, and medical/physical guidelines are established for those jobs. Physical exams are specific for the job class. 3. The program is projecting a net annual savings of over $208,000 for workers' compensation back injury claims. PMID- 2108688 TI - The ratio of macrophage prostaglandin and leukotriene synthesis is determined by the intracellular free calcium level. AB - The induction of eicosanoid synthesis in various cell types by different physiological stimuli is dependent on an increase in the intracellular calcium level and stimulation of the protein kinase C (PKC). In a model system this can be mimicked by using calcium ionophores and direct PKC activators. In mouse peritoneal macrophages calcium ionophores induced the formation of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4). A synergistic enhancement of both eicosanoids could be achieved by simultaneous addition of the calcium ionophore A23187 together with a suboptimal dose of the direct protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA). Low concentrations of the ionophore, resulting in only marginally increased intracellular calcium levels, led to a more than additive prostaglandin E2 production in combination with TPA. Higher concentrations of A23187 together with TPA favoured LTC4 synthesis, whereas PGE2 levels at the same time were even diminished. This observed shift from prostaglandin to leukotriene formation was amplified by simultaneous addition of indomethacin. Manganese as inhibitor of the A23187-induced calcium influx decreased PGE2 synthesis. On the other hand, in the presence of manganese LTC4 production was also inhibited at high concentrations of A23187 but elevated in the absence or at low doses of A23187. Our data provide evidence that in macrophages the ratio of cyclooxygenase and lipoxygenase products caused by mediators, acting via the phospholipase C or D/PKC signal transduction pathway, is regulated by the extent of the intracellular calcium increase. PMID- 2108689 TI - Differential coupling between muscarinic receptors and G-proteins in regions of the rat brain. AB - The coupling of muscarinic receptors to G-proteins in various regions of the rat brain was assessed by measuring carbachol-stimulated, low-Km GTPase. The inhibition of carbachol-stimulated GTPase by the M1-selective antagonist pirenzepine was compared to the affinity of pirenzepine for various nuclei within the regions as measured autoradiographically. The rank order of potency of carbachol for stimulating GTPase in various brain regions was similar to that for binding to receptors in those areas. The maximal specific activity (efficacy) of carbachol-stimulated GTPase varied independently of the distribution of total receptors or receptor subtypes. The overall potency of pirenzepine for inhibiting carbachol-stimulated GTPase was not correlated with the overall affinity of pirenzepine for muscarinic receptors in the regions. Comparing results in various brain regions, the data suggest that there are differences in the efficiency of coupling between muscarinic receptors and G-proteins. For example, the pons medulla appeared to have a small population of pirenzepine-sensitive (M1 or M4) receptors that were coupled very efficiently to G-proteins, whereas in the hippocampus all muscarinic receptors, most of which are pirenzepine-sensitive, appeared to be weakly coupled to G-proteins. It is suggested that variable interactions between receptors and G-proteins may be an important factor in the overall coupling between receptor occupancy and cellular responses to acetylcholine as well as other hormones and transmitters. PMID- 2108691 TI - The effectiveness of helmets in reducing all-terrain vehicle injuries and deaths. AB - This article examines the effectiveness of helmets in reducing all-terrain vehicle (ATV) related deaths and head injuries, conditional on the occurrence of injury producing accidents. A logit regression model is used to analyze cross section data on ATV-related fatal and nonfatal injuries, and to determine the factors that are associated with deaths and head injuries. The results suggest that, given an accident resulting in injury or death, helmet use reduces the risk of death by about 42%, and could reduce the likelihood that a given nonfatal injury involves the head by about 64%. Other factors that are associated with the risk of fatality for injury accidents include the use of alcohol or drugs, driving on paved roads, the driver's age and sex, and the vehicle's engine size. A benefit-cost analysis of helmet use is conducted and policy implications are discussed. PMID- 2108692 TI - Feedback-inhibition of growth hormone (GH) secretion in fowl: GH-induced down regulation of thyrotrophin-releasing hormone binding to pituitary membranes. AB - Administration of ovine GH to immature domestic fowl blunted their subsequent GH response to thyrotrophin-releasing hormone (TRH), a GH secretagogue in birds. The in-vivo administration of GH also reduced the ability of radiolabelled TRH to bind to plasma membranes of the pituitary caudal lobe, in which GH cells predominate. These inhibitory effects of GH were mediated by extrapituitary actions, since GH had no direct inhibitory effects on TRH-induced GH release or on pituitary TRH binding in vitro. GH inhibition of GH secretion and TRH binding would not appear to be mediated by hypothalamic somatostatin (SRIF) or peripheral somatomedin (IGF-I), since SRIF and IGF-I had no direct effects in vitro. PMID- 2108693 TI - Rhodopsin expressed in Chinese hamster ovary cells regulates adenylyl cyclase activity. AB - The cDNA encoding bovine opsin was transfected into Chinese hamster ovary (CHO) cells to generate stable clones expressing the rod cell photoreceptor protein. Cells expressing opsin, when incubated in 11-cis retinal and exposed to light, inhibited forskolin-stimulated adenylyl cyclase activity. Rhodopsin-mediated inhibition of adenylyl cyclase was prevented by treatment of cells with pertussis toxin. In the same cells, thrombin stimulated phosphatidylinositol hydrolysis through G protein-mediated pathways, but rhodopsin neither significantly influenced the action of thrombin nor stimulated phosphatidylinositol hydrolysis. Our findings indicate that rhodopsin selectively regulates a Gi protein in intact CHO cells that is coupled to adenylyl cyclase but not to phospholipase C. PMID- 2108694 TI - Stable expression of human cytochrome P450IA2 cDNA in a human lymphoblastoid cell line: role of the enzyme in the metabolic activation of aflatoxin B1. AB - A human lymphoblastoid cell line stably expressing a human cytochrome P450IA2 cDNA was developed. This recombinant cell line displayed P450IA2 protein and estradiol 2-hydroxylase activity, neither of which was detected in the parental cell line. The recombinant cell line was also approximately 1000-fold more sensitive to the cytotoxicity and mutagenicity of the carcinogenic mycotoxin aflatoxin B1 than was the parent cell line. The increase in mutagenicity was supported by a corresponding increase in the level of aflatoxin B1 binding to DNA in cells expressing P450IA2 relative to control cells. PMID- 2108695 TI - Proteoglycan-lymphocyte association in the development of hypertrophic scars. AB - Parallel histological stains and immunohistological stains were made of hypertrophic scars and normal scars in order to identify the type of cells and associated proteoglycans present in perivascular cuffs in hypertropic scars. Tissue sections were treated with monoclonal antibodies which specifically recognize T-cells and unsulphated, 4-sulphated and 6-sulphated chondroitin proteoglycans. There was a striking association between the perivascular lymphocytic infiltration and chondroitin-4-sulphate, which may be an important contributory factor in the development of hypertrophic scars. PMID- 2108696 TI - Topical antimicrobial testing of burn wound microorganisms: evaluation of a new technique. AB - A new system of determining susceptibility of burn wound microorganisms to topical antimicrobial therapy was studied. The new method, TOPITEST, employs a methacrylate vehicle impregnated with various antimicrobial agents and an agar overlay. Test plates can be inoculated by a direct swab culture of the wound or with micro-organisms isolated by other methods. This new technique was compared to an agar well diffusion (AWD) method using commercially compounded antimicrobials and biopsy-recovered organisms. The new test method provided comparable results to the more established AWD test when using biopsy-recovered organisms. Using the swab culture technique, however, TOPITEST had a high rate of failure to recover sufficient organisms from the burn wound for testing. The new, more standardized test provided results earlier than the AWD test, but may prove to be less cost effective. PMID- 2108697 TI - [Certification and quality of care]. PMID- 2108698 TI - [Psychiatry in Turin--a reconnoiter]. PMID- 2108699 TI - [American method for The Netherlands also? Phaneuf's nursing audit applied in Leyenburg hospital]. PMID- 2108700 TI - [From taboo to policy? (3). Homosexuality and the TvZ. An exploratory study: 1930 1990]. PMID- 2108701 TI - [CVA in high gear--the best possible treatment]. PMID- 2108702 TI - [The use of DMS III]. PMID- 2108703 TI - [National study of possible prevention of HIV-related pneumonia]. PMID- 2108704 TI - 6-Hydroxydopamine lesion of the rat prefrontal cortex increases locomotor activity, impairs acquisition of delayed alternation tasks, but does not affect uninterrupted tasks in the radial maze. AB - The role of mesocortical dopamine neurons in locomotion and acquisition of various delayed and uninterrupted maze tasks was investigated in the rat. Dopaminergic terminals of the medial prefrontal cortex were lesioned by stereotaxically guided injections of the selective neurotoxin 6-hydroxydopamine (6-OHDA), while noradrenergic neurons were protected by systemically administered desipramine. 6-OHDA lesions resulted in a selective depletion of dopamine and its metabolite, dihydroxyphenylacetic acid, in the prefrontal cortex but not in subcortical structures. Prefrontal serotonin was not depleted. 6-OHDA-cloned rats performed uninterrupted alternation tasks (spontaneous and reinforced alternation) in the radial maze in the same manner as controls, whereas performance of delayed alternation in the T-maze and the radial maze was impaired in lesioned rats. In addition, locomotor activity during maze performance was increased in lesioned rats. Based on the hypothesis that increased motor activity and impaired delayed alternation performance are due to increased susceptibility to interfering stimuli, we propose tentatively that prefrontal dopamine may function to suppress interference during the delay period of certain cognitive tasks. PMID- 2108705 TI - The human immunoglobulin kappa locus and some of its acrobatics. A review presented on the occasion of receiving the "Otto-Warburg-Medaille" of Gesellschaft fur Biologische Chemie at Osnabruck on September 13, 1989. PMID- 2108706 TI - Parenteral nutrition. Pharmaceutical problems of compatibility and stability. AB - A typical All-in-One (AIO) parenteral nutrition mixture in a 3-litre polymeric infusion bag will consist of lipid emulsion, amino acids, glucose, electrolytes, trace elements and vitamins. This varied mixture of chemical entities provides the potential for a number of chemical and physicochemical interactions that can compromise the clinical safety and efficacy of the product. The destabilisation of the lipid emulsion in the presence of electrolytes is a major problem. Although a predictive equation for the maximum concentrations of mono-, di- and trivalent ions causing instability has been proposed, it is too simplistic to be of significant value. The reasons for this are discussed as well as the stability implications of other additives to the parenteral nutrition mixture. PMID- 2108707 TI - Deficient activity of nucleotide binding regulatory protein coupled with PGE2 receptor in renal medulla of spontaneously hypertensive rats. AB - Prostaglandin (PG) E2 receptor-adenylate cyclase system was studied in the kidney of 12-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) to evaluate the role of this system in hypertension. PGE2 receptors were determined by a radioligand binding method using [3H]-PGE2. Adenylate cyclase responses to PGE2, sodium fluoride (NaF) and forskolin were also measured. The concentration of PGE2 receptor was increased in SHR compared with WKY. PGE2- and NaF-stimulated adenylate cyclase activities were significantly lower in SHR than WKY. There was no significant difference in forskolin-stimulated adenylate cyclase activity between SHR and WKY. NaF activates the nucleotide binding regulatory protein (G-protein) and forskolin directly activates the catalytic unit. These results indicate that the activity of G-protein coupled with renal PGE2 receptors is deficient in SHR. This defect may contribute to the elevation of blood pressure, through sodium retention. PMID- 2108708 TI - Differential expression of immediate early genes in the hippocampus and spinal cord. AB - We have demonstrated that immediate early genes can be differentially activated within the central nervous system. We examined the effects of tetanic stimulation in the hippocampus and of noxious sensory stimulation of the spinal cord on the expression of eight immediate early genes. Induction of long-term potentiation (LTP) in the dentate gyrus resulted in an increase in mRNA and protein for NGFI-A (also termed Zif/268, Egr-1, or Krox 24), and less consistently for jun-B mRNA. No increase was seen for c-fos, NGFI-B, c-jun, jun-D, SRF, or PC4 mRNAs. Blockade of the NMDA receptor prevented the induction of both LTP and NGFI-A mRNA in the dentate gyrus. However, commissural stimulation, which prevented the induction of LTP, resulted in bilateral activation of all the genes examined, including NGFI A. No change was seen in animals trained in a water maze. These results suggest that no simple relationship exists between LTP, spatial learning, and immediate early gene induction. Stimulation of sensory fibers resulted in an increase in mRNA for NGFI-A, c-fos, SRF, NGFI-B, and c-jun in spinal cord neurons. Blockade of the NMDA receptor had no effect on immediate early gene induction in the spinal cord. PMID- 2108709 TI - Antibody to blood group glycosyltransferases in a patient transplanted with an ABO incompatible bone marrow. AB - In the plasma of a blood group B recipient who was transplanted with a blood group O bone marrow, we investigated an antibody to inhibit the activities of blood group A- and B-glycosyltransferases. When B lymphocytes from the patient were transformed with Epstein-Barr virus, a few clones producing antibodies to B transferase were obtained. PMID- 2108710 TI - [Social needs of the institutionalized elderly in long-term care and their perception of self and others]. AB - In this study social needs of the elderly are examined using the closeness needs of Yura and Walsh (1988). With a little material it is described how the elderly and his relative experience appreciation, acceptance, feeling of togetherness and the needs of closeness of the elderly and his body image and sexual integrity. The study was implemented in a geriatric hospital as half structured theme interviews. Ten elderly and one relative of each elderly were selected to interview. The interviewed elderly experienced that the relatives and nurses were appreciated them being matter-of-fact and helpful. The elderly described their own health better than that of the others in the same room. The closest relatives formed the network of their social support. The elderly had to become adjusted to their incompetence to move and their needs of help. The relatives thought with the same way. PMID- 2108711 TI - Non-A, non-B hepatitis and dentistry. AB - Non-A, non-B hepatitis (hepatitis C) is a viral infection(s) transmitted mainly by blood and blood products. Infection is usually asymptomatic, but typically followed by chronic infection, frequently with chronic liver disease. Although probably less than 1% of the UK population (and hence dental patients) are infected, groups at high risk for other blood-borne infections are also at risk for non-A, non-B hepatitis. Immunisation against hepatitis B cannot protect against non-A, non-B hepatitis; recommended cross-infection procedures must suffice to protect patients and staff. PMID- 2108712 TI - Prophylactic use of phenoxymethylpenicillin and tinidazole in mandibular third molar surgery, a comparative placebo controlled clinical trial. AB - A clinical double-blind placebo controlled trial was carried out in 136 patients to test the value of the prophylactic use of phenoxymethylpenicillin and tinidazole in mandibular third molar surgery. The three patient groups were uniform with regard to the background data such as age and weight of the patients and the clinical status of the operated tooth, as well as to the observations made at surgery. No statistically significant differences were found between the study groups in the parameters used for evaluation. The results indicate that neither penicillin nor tinidazole have more effect on postoperative complications following operative extraction of wisdom teeth, than placebo tablets. PMID- 2108713 TI - Cloning, sequencing, expression, and site-directed mutagenesis of the gene from Clostridium perfringens encoding pyruvoyl-dependent histidine decarboxylase. AB - The DNA encoding pyruvoyl-dependent histidine decarboxylase (HisDCase) of Clostridium perfringens was cloned, sequenced, and overexpressed in Escherichia coli. The gene encodes a single polypeptide of 320 amino acids, Mr 35,526, demonstrating that clostridial HisDCase, which has an (alpha beta)6 structure, is synthesized as a precursor (proHisDCase, pi 6). No pi subunits of proHisDCase were observed in crude or purified preparations of the cloned HisDCase; they appear to undergo rapid cleavage in vivo to the alpha (Mr 24,887) and beta (Mr 10,526) subunits characteristic of this HisDCase. This cleavage occurs between Ser-96 and Ser-97; Ser-97 gives rise to the catalytically essential pyruvoyl group blocking the N-termini of the alpha subunits of the active enzyme. When Ser 97 was converted to an alanyl residue by site-specific mutagenesis, the expressed, inactive protein (pi' 6) contained a single peptide species (pi', Mr 35,510) that was not cleaved either in vivo or in vitro. These results support previous conclusions that activation of the wild-type clostridial proenzyme occurs via nonhydrolytic serinolysis. Although clostridial HisDCase has only a 47% sequence similarity to HisDCase from Lactobacillus 30a, all of the residues known to be important for substrate binding and catalytic action of the Lactobacillus HisDCase are conserved in the C. perfringens enzyme. While the encoded N-terminal Met of clostridial HisDCase is removed by E. coli, the cloned enzyme retains a 10-residue presequence (NKNLEANRNR) not present in the mature enzyme isolated from C. perfringens. PMID- 2108714 TI - Cryoenzymology of staphylococcal beta-lactamase: trapping a serine-70-linked acyl enzyme. AB - Various cryosolvents were investigated for their suitability in cryoenzymological experiments with beta-lactamase from Staphylococcus aureus PC1. On the basis of the minimal effects on the catalytic and structural properties of the enzyme, ternary solvents containing ethylene glycol, methanol, and water were found most suitable. The interaction of beta-lactamase with a number of substrates was studied at subzero temperatures. In general, the reaction profiles were similar to those in aqueous solution at above-zero temperatures, with the exception of the slower rates. For cephalosporin substrates, such as PADAC, in which the 3' substituent may leave to form a more stable form of the acyl-enzyme [Faraci, W., & Pratt, R. (1985) Biochemistry 24, 903-910], this intermediate could be readily stabilized at subzero temperatures. At -40 degrees C the slow rate of deacylation in the reaction with the chromophoric substrate 6 beta [(furylacryloyl)amino]penicillanic acid permitted the acyl-enzyme to be stoichiometrically accumulated. This intermediate was then stabilized at low pH with trifluoroacetic acid. Isolation by centrifugal gel filtration, followed by pepsin digestion, gave a penicilloyl-labeled peptide which was isolated by HPLC. Subsequent trypsinolysis of this peptide gave a single labeled peptide, corresponding to the octapeptide surrounding the active-site serine, Ser-70. PMID- 2108715 TI - Structural, functional, and subunit assembly properties of hemoglobin Attleboro [alpha 138 (H21) Ser----Pro], a variant possessing a site maturation at a critical C-terminal residue. AB - Hemoglobin Attleboro, a new alpha-chain variant with a substitution of proline for serine at position 138 (H21), was found to be a noncooperative high-affinity hemoglobin (P50 = 0.26 mmHg at pH 7 and 20 degrees C) which lacked an alkaline Bohr effect. Addition of 2,3-diphosphoglycerate (DPG) or inositol hexaphosphate (IHP) led to a decrease in oxygen affinity but to no alteration in either Bohr effect or cooperativity. Ligand binding kinetics studies revealed an overall rate of oxygen dissociation at pH 7.0 and 20 degrees C that was 2.7-fold slower than that for Hb A. At pH 8.5, the kinetic profile was identical with that at pH 7, confirming the absence of a Bohr effect for this variant hemoglobin. Measurement of the rate of oxygen dissociation with carbon monoxide replacement indicated a lack of cooperativity. Sedimentation velocity experiments yielded s20,w values of 2.8 and 4.3 for 65 microM solutions of oxyhemoglobins Attleboro and A, respectively (indicating an enhancement in the oxy dimer population of this variant). Studies of the carbon monoxide combination of this variant revealed an association rate 20-fold faster than that for Hb A; only in the presence of a 1000-fold molar excess of IHP was there a significant reduction in the overall rate. Rapid-scan and traditional stopped-flow experiments conducted in the Soret Soret region demonstrated an alteration in the structure and rate of assembly of the deoxy tetramer of Hb Attleboro relative to that of Hb A. The abnormal properties of this hemoglobin variant can be attributed to major perturbations in the C-terminal region. PMID- 2108716 TI - Intracellular modification of human apolipoprotein AII (apoAII) and sites of apoAII mRNA synthesis: comparison of apoAII with apoCII and apoCIII isoproteins. AB - We have studied the intracellular modifications of human apoAII by pulse-chase labeling of HepG2 cell cultures with [35S]methionine or [3H]arginine followed by two-dimensional analysis and autoradiography of the radiolabeled apoAII isoproteins. A short (5.0-min) pulse showed the presence of a precursor form of apoAII (pI = 5.75) designated proapoAII or apoAII3. A 5-10-min chase resulted in a decrease in the relative concentration of the proapoAII coupled with an increase in the relative concentration of a new form (pI = 5.3) designated modified proapoAII or apoAII1. Longer chase resulted in the appearance of the plasma apoAII form and at least five other acidic apoAII isoproteins in the cell lysate and the culture medium. Labeling with [3H]arginine showed that apoAII isoproteins designated 3, 1, -1, and -3 contained the prosegment whereas isoproteins designated 1a, 0, -1a, -2a, -3a, and -4a did not. Comparison of nascent apoAII, apoCII, and apoCIII isoproteins revealed that they were distinctly different on the two-dimensional gels. Neuraminidase treatment converted the acidic apoAII isoproteins to isoproteins 1a and 0 (modified and plasma apoAII forms). The combined data are consistent with the following intra- and/or extracellular modifications of apoAII: (a) modification of the apoAII which results in the net loss of two positive charges; (b) glycosylation of the modified proapoAII with carbohydrate chains containing sialic acid; (c) proteolytic removal of the prosegment and cyclization of the N-terminal glutamine. Analysis of apoAII mRNA distribution in 13 fetal human tissues as well as in cell lines of human origin showed abundance of apoAII mRNA in liver and HepG2 cells and only traces in the intestine. PMID- 2108717 TI - Effect of DNA polymerase inhibitors on DNA repair in intact and permeable human fibroblasts: evidence that DNA polymerases delta and beta are involved in DNA repair synthesis induced by N-methyl-N'-nitro-N-nitrosoguanidine. AB - The involvement of DNA polymerases alpha, beta, and delta in DNA repair synthesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in human fibroblasts (HF). The effects of anti-(DNA polymerase alpha) monoclonal antibody, (p-n-butylphenyl)deoxyguanosine triphosphate (BuPdGTP), dideoxythymidine triphosphate (ddTTP), and aphidicolin on MNNG-induced DNA repair synthesis were investigated to dissect the roles of the different DNA polymerases. A subcellular system (permeable cells), in which DNA repair synthesis and DNA replication were differentiated by CsCl gradient centrifugation of BrdUMP density-labeled DNA, was used to examine the effects of the polymerase inhibitors. Another approach investigated the effects of several of these inhibitors on MNNG-induced DNA repair synthesis in intact cells by measuring the amount of [3H]thymidine incorporated into repaired DNA as determined by autoradiography and quantitation with an automated video image analysis system. In permeable cells, MNNG-induced DNA repair synthesis was inhibited 56% by 50 micrograms of aphidicolin/mL, 6% by 10 microM BuPdGTP, 13% by anti-(DNA polymerase alpha) monoclonal antibodies, and 29% by ddTTP. In intact cells, MNNG-induced DNA repair synthesis was inhibited 57% by 50 micrograms of aphidicolin/mL and was not significantly inhibited by microinjecting anti-(DNA polymerase alpha) antibodies into HF nuclei. These results indicate that both DNA polymerases delta and beta are involved in repairing DNA damage caused by MNNG. PMID- 2108718 TI - Enthalpic and entropic contributions to actin stability: calorimetry, circular dichroism, and fluorescence study and effects of calcium. AB - The delta H associated with the thermal unfolding of G-actin has been determined by differential scanning calorimetry (DSC) to be 142 +/- 5 kcal/mol, with the Tm (melting temperature) at 57.2 +/- 0.5 degrees C, at pH 8.0 (heating rate 0.5 K/min). The transition is broad and cannot be treated as a single transition that mimics a two-state process, suggesting the existence of domains. Deconvolution is done to fit it into two quasi-independent two-state transitions. For F-actin, the transition is more cooperative, with a cooperative ratio (the ratio of van't Hoff enthalpy and calorimetric enthalpy) of 1.4, indicating intermonomer interaction. The delta H of the thermal unfolding of F-actin is 162 +/- 10 kcal/mol with a Tm at 67.0 +/- 0.5 degrees C. A state of G-actin similar to that of the heat denatured form, designated D-actin, is obtained by removing tightly bound Ca2+ with EGTA. The DSC-detectable cooperative transition is completely lost when the free calcium concentration of the medium is 1 x 10(-11) M or lower, using a Ca2+/EGTA buffer system. However, circular dichroism (CD) shows that the helix content of actin, 32% in the G-form, is only partially reduced to 19% in this apo form. The CD spectrum and the helix content of the calcium-depleted actin are almost identical with those of the heat-denatured D form. This loss of 40% of the native helical content is irreversible in both cases. The remaining 60% of the native helical content cannot be further eliminated by heating to 95 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108719 TI - Characterization of zero-length cross-links between rabbit skeletal muscle troponin C and troponin I: evidence for direct interaction between the inhibitory region of troponin I and the NH2-terminal, regulatory domain of troponin C. AB - Interactions between troponin C (TnC) and troponin I (TnI) play an important role in the Ca2(+)-dependent regulation of vertebrate striated muscle contraction. Previous attempts to elucidate the molecular details of TnC-TnI interactions, mainly involving chemically modified proteins or fragments thereof, have led to the widely accepted idea that the "inhibitory region" (residues 96-116) of TnI binds to an alpha-helical segment of TnC comprising residues 89-100 in the nonregulatory, COOH-terminal domain. In an attempt to identify other possible physiologically important interactions between these proteins, 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide (EDC) was used to produce zero-length cross links in the complex of rabbit skeletal muscle TnC and TnI. TnC was activated with EDC and N-hydroxysuccinimide (NHS) and then mixed with an equimolar amount of TnI [Grabarek, Z., & Gergely, J. (1988) Biophys. J. 53, 392a]. The resulting cross-linked TnCXI was cleaved with cyanogen bromide, trypsin, and Staphylococcus aureus V8 protease (SAP). Cross-linked peptides were purified by reverse-phase HPLC and characterized by sequence analysis. The results indicated that residues from the regulatory Ca2(+)-binding site II in the NH2-terminal domain of TnC (residues 46-78) formed cross-links with TnI segments spanning residues 92-167. The most highly cross-linked residues in TnI were Lys-105 and Lys-107, located in the inhibitory region. These results yield the first evidence for an interaction between the N-terminal domain of TnC and the inhibitory region of TnI. PMID- 2108720 TI - Two-dimensional NMR studies of staphylococcal nuclease. 1. Sequence-specific assignments of hydrogen-1 signals and solution structure of the nuclease H124L thymidine 3',5'-bisphosphate-Ca2+ ternary complex. AB - Staphylococcal nuclease H124L is a recombinant protein produced in Escherichia coli whose sequence is identical with that of the nuclease produced by the V8 variant of Staphylococcus aureus. The enzyme-metal ion activator-nucleotide inhibitor ternary complex, nuclease H124L-thymidine 3',5'-bisphosphate-Ca2+, was investigated by two-dimensional (2D) NMR techniques. Efficient overproduction of the enzyme facilitated the production of random fractionally deuterated protein, which proved essential for detailed NMR analysis. 1H NMR spin systems were analyzed by conventional 2D 1H[1H] methods: COSY, relayed COSY, HOHAHA, and NOESY. Assignments obtained by 1H NMR experiments were confirmed and extended by 1H-13C and 1H-15N heteronuclear NMR experiments [Wang, J., Hinck, A. P., Loh, S. N., & Markley, J. L. (1990) Biochemistry (following paper in this issue)]. Spectra of the ternary complexes prepared with protein at natural abundance and at 50% random fractional deuteration provided the information needed for sequence specific assignments of 121 of the 149 amino acid residues. Short- and intermediate-range NOE connectivities allowed the determination of secondary structural features of the ternary complex: three alpha-helical domains and three antiparallel beta-pleated sheets with several reverse turns. A number of nonsequential long-range HN-HN and H alpha-HN connectivities revealed additional information about the spatial arrangement of these secondary structural elements. The solution structure of this ternary complex shows a close correspondence to the crystal structure of the nuclease wt-thymidine 3',5'-bisphosphate-Ca2+ ternary complex [Cotton, F. A., Hazen, E. E., & Legg, M. J. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 2551-2555]. PMID- 2108721 TI - Site-directed mutagenesis of glycine-14 and two "critical" cysteinyl residues in Drosophila alcohol dehydrogenase. AB - Three amino acid residues (glycine-14, cysteine-135, and cysteine-218) previously speculated to be important for the structure and function of Drosophila melanogaster alcohol dehydrogenase have been investigated by using site-directed mutagenesis followed by kinetic analysis and chemical modification. Mutating glycine-14 to valine (G14V) virtually inactivates Drosophila ADH, and substitution of alanine at this position (G14A) causes a 31% decrease in activity. Thermal denaturation and kinetic and inhibition studies further demonstrate that replacing glycine-14 with either alanine or valine leads to structural changes in the NAD binding domain. These results provide direct evidence for the role played by glycine-14 in maintaining the correct conformation in the NAD binding domain. On the other hand, changing of cysteine 135, -218, or both to alanine (C135A, C218A, and C135A/C218A) causes no decrease in the catalytic activity of the enzyme, indicating that neither of the cysteinyl residues is essential for catalysis. C135A and wild-type enzyme are both inactivated by DTNB. In contrast, C218A and C135A/C218A are unaffected by DTNB treatment. DTNB modification of cysteine-218 can be prevented by the substrates NAD and 2-propanol, suggesting that cysteine-218 may be in the vicinity of the active site. Cysteine-135 which is normally insensitive to DTNB becomes accessible in the presence of 2-propanol and/or NAD, suggesting a conformational change induced by binding of these substrates. PMID- 2108722 TI - A synthetic peptide corresponding to human FSH beta-subunit 33-53 binds to FSH receptor, stimulates basal estradiol biosynthesis, and is a partial antagonist of FSH. AB - We have previously shown that hFSH-beta 34-37 (KTCT) and 49-52 (TRDL) inhibit binding of 125I-hFSH to FSH receptor in calf testis membranes and that hFSH-beta 33-53, which encompasses these tetrapeptides, inhibits binding with increased potency. hFSH-beta 33-53 rapidly dimerizes under conditions utilized in the receptor binding assay (pH 7.5) so that the binding inhibition reported earlier was due to the hFSH-beta 33-53 dimer rather than the monomer. At pH 6.5, conversion to dimer does not occur, and binding inhibition could be unequivocally attributed to the monomer. Radioiodinated and alkylated hFSH-beta 33-53 binds to the FSH receptor with a Kd = (5.5 +/- 1.4) X 10(-5) M. The biological activity of hFSH-beta 33-53 was assessed by its ability to affect the conversion of androstenedione to estradiol in rat Sertoli cells cultures. FSH-beta 33-53 behaved as a partial antagonist of the FSH-induced estradiol synthesis. The required incubation medium, however, contains cystine as well as cystine, which rapidly forms a hFSH-beta Cys-(51)-S-S-Cys derivative at the pH of the incubation, 7.4. When hFSH-beta 33-53 was converted either to the hFSH-beta Cys(51)-S-S-Cys or to a carboxymethylated derivative, inhibition of FSH-induced estradiol synthesis still was observed. This result demonstrates that the free R SH group at Cys51 is not responsible for the inhibition. FSH-beta 33-53 also significantly stimulated basal levels of estradiol synthesis, but not to maximal levels observed with FSH (partial agonist). Neither the carbohydrate content of hFSH-beta nor the alpha subunit of FSH appears to be essential for signal transduction and expression of the hormone effect of FSH-beta 33-53. PMID- 2108723 TI - GTP analogues interact with the tubulin exchangeable site during assembly and upon binding. AB - The question of whether nonhydrolyzable nucleotide analogues and other nucleoside triphosphates support tubulin assembly was addressed. Tubulin which contained residual GTP at the exchangeable site polymerized in the absence of added GTP in the presence of DMSO or glycerol. After maximum absorbance was reached, disassembly occurred at a slow rate. When 0.5 mM GMPPCP, GMPPNP, or ATP was included in the assembly reaction, disassembly did not occur, and about 0.1 mol of these nucleotides per mole of tubulin was incorporated into the protein. When 5 mM nucleotide was used or alkaline phosphatase was included in the case of the nonhydrolyzable analogues, a greater amount of assembly occurred and about 0.7 0.8 mol of analogue was incorporated. The products of the assembly reaction were cold-labile microtubules and protofilament ribbons. After cold-depolymerization of the microtubules and ribbons, a second cycle of assembly produced some microtubules, but cold-stable amorphous polymers were the major product. In addition, when GTP at the exchangeable site was first removed by a cycle of assembly, followed by depolymerization, assembly in the presence of GMPPCP, GMPPNP, or ATP produced a mixture of microtubules and cold-stable polymers, both of which contained bound analogue. Incorporation of GMPPCP, GMPPNP, or ATP into polymerized tubulin always occurred at the expense of GDP at the exchangeable site, the content of which decreased correspondingly. Incubation of tubulin with 5 mM GMPPCP, GMPPNP, or ATP under nonassembly conditions also displaced GDP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108724 TI - Molecular weight determination of an active photosystem I preparation from a thermophilic cyanobacterium, Synechococcus elongatus. AB - An active photosystem I (PSI) complex was isolated from the thermophilic cyanobacterium Synechococcus elongatus by a procedure consisting of three steps: First, extraction of photosystem II from the thylakoids by a sulfobetaine detergent yields PSI-enriched membranes. Second, the latter are treated with Triton X-100 to extract PSI particles, which are further purified by preparative isoelectric focusing. Third, anion-exchange chromatography is used to remove contaminating phycobilisome polypeptides. The purified particles show three major bands in sodium dodecyl sulfate gel electrophoresis of apparent molecular mass of 110, 15, and 10 kDa. Charge separation was monitored by the kinetics of flash induced absorption changes at 820 nm. A chlorophyll/P700 ratio of 60 was found. When the particles are stored at 4 degrees C, charge separation was stable for weeks. The molecular mass of the PSI particles, determined by measurement of zero angle neutron scattering intensity, was 217,000 Da. The PSI particles thus consist of one heterodimer of the 60-80-kDa polypeptides and presumably one copy of the 15- and 10-kDa polypeptides, respectively. PMID- 2108725 TI - 19F NMR study of the myosin and tropomyosin binding sites on actin. AB - Actin was labeled with pentafluorophenyl isothiocyanate at Lys-61. The label was sufficiently small not to affect the rate or extent of actin polymerization unlike the much larger fluorescein 5-isothiocyanate which completely inhibits actin polymerization [Burtnick, L. D. (1984) Biochim. Biophys. Acta 791, 57-62]. Furthermore, the label resonances in the 376.3-MHz 19F NMR spectrum were unaffected by actin polymerization. However, the binding of the relaxing protein tropomyosin resulted in the fluorinated Lys-61 resonances broadening out beyond detection due to a substantial increase in the effective correlation time of the label. Similarly, the binding of myosin subfragment 1 to F-actin resulted in the dramatic broadening of the labeled Lys-61 resonances. Thus, Lys-61 on actin appears to be closely associated with the binding sites for both tropomyosin and myosin, suggesting that both these proteins can compete for the same site on actin. The other region of actin known to be involved in myosin binding, Cys-10, was found to be more remote from the actin-actin interfaces than Lys-61. Labels on Cys-10 exhibited substantially greater mobility than fluorescein 5 isothiocyanate attached to Lys-61 which appeared to be held down on the surface of the actin monomer. This may sterically hinder the actin-actin interaction about 1 nm from the tropomyosin/myosin binding site. PMID- 2108726 TI - Lipid transfer between human plasma low-density lipoprotein and a triolein/phospholipid microemulsion catalyzed by insect hemolymph lipid transfer particle. AB - Lipid transfer between human plasma low-density lipoprotein (LDL) and an LDL-size microemulsion of triolein and phosphatidylcholine stabilized with human apolipoprotein A-I was catalyzed by the lipid transfer particle from hemolymph of the tobacco hornworm (Manduca sexta). Net transfer of phospholipid and triacylglycerol from the emulsion to LDL was observed and the apparent initial rates of transfer were dependent on the amount of catalyst. Net transfer of phospholipid mass was twice as much as that of triacylglycerol with respect to both the initial rate and the final equilibrium state. The final amount of net transfer of both lipids was dependent upon the initial ratio of LDL: microemulsion present in the incubation mixture up to 1:1 on the basis of phospholipid. The microemulsion lipid composition was maximally altered from an initial weight ratio of 1.09 +/- 0.08 (phospholipid/triolein) to 0.90 +/- 0.03 by this reaction. Further increase of LDL in the incubation caused neither further net transfer nor further change in the lipid composition of the microemulsion. The catalyst neither affected spontaneous transfer of free cholesterol between the emulsion and LDL nor enhanced cholesteryl ester transfer in this reaction system. As a result of the facilitated reaction, LDL gained a significant amount of phospholipid and triacylglycerol causing up to an 8% increase in core lipids and 14% in phospholipid. Some free cholesterol is recovered in the emulsions via spontaneous exchange. Transfer or exchange of apolipoproteins during the course of facilitated lipid transfer did not occur. PMID- 2108727 TI - Apolipoprotein A-I and apolipoprotein SAA half-lives during acute inflammation and amyloidogenesis. AB - The half-lives of two apolipoproteins of mouse high-density lipoproteins, apo A-I and apo SAA, were determined in normal animals and compared with those having an inflammatory condition, or inflammation leading to AA amyloid deposition. The apo A-I half-life was considerably shorter in animals with inflammation and in those that were preamyloidotic, than in controls (t1/2 of 3-3.5 h vs. 10-12 h). The average loss of apo A-I in controls over the first 10 h was 31.1 micrograms/ml per h, while that in inflamed animals was 58.7 micrograms/ml per h a 2-fold increase in apo A-I clearance. The apo SAA half-life was similar in all groups of animals and was of the order of 1.5 h. The concentration of apo SAA during inflammation is however considerably higher (500-1000-fold) than in controls, which implies a much greater clearance rate during inflammation and involving a process which is apparently not saturable. In addition to hypertriglyceridemia and Tangier's disease, ordinary acute inflammation can now be added to those pathological conditions which lead to a significant decrease in apo A-I half life. PMID- 2108728 TI - Inhibition of mucin secretion in a colonic adenocarcinoma cell line by DIDS and potassium channel blockers. AB - The factors which influence the exocytosis of mucins are not well characterized. Since the physical properties of mucins may be affected significantly by the co secretion of electrolytes and water, we studied the relationship between ion movement and mucin secretion in T84 cells, a human colonic adenocarcinoma cell line which has been well characterized with respect to apical chloride secretion. Secretion of mucin was assessed by immunoassay of mucin appearing in the medium within 30 min of stimulation. Cells were grown on plastic in DMEM/Ham's F12 medium and experiments were carried out at 70% confluence. Mucin secretion was stimulated by the calcium ionophore A23187, or A23187 plus vasoactive intestinal polypeptide. Stimulated mucin secretion was not affected by loop diuretics (furosemide (1 x 10(-3) M) or bumetanide (1 x 10(-4) M)), with or without the addition of ouabain (5 x 10(-5) M) and amiloride (1 x 10(-5) M), making it unlikely that transcellular chloride movements in necessary for mucin secretion. However, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; (1 x 10(-5) and 5 x 10(-5) M) and three potassium channel blockers BaCl2 (1 x 10(-3) and 5 x 10( 3) M), tetraethylammonium chloride (1 x 10(-2) M) and quinine (5 x 10(-4) M) inhibited mucin secretion. A DIDS-sensitive chloride channel or chloride/bicarbonate exchanger and a Ca2(+)-dependent potassium channel may play important roles in mucin secretion. Since plasma membranes are sparingly permeable to DIDS, the DIDS-sensitive site is likely to be on the apical plasma membrane, perhaps at an initiation locus for exocytosis. PMID- 2108730 TI - Evidence for functional differences between the two sites of rabbit transferrin: effects of serum and carbon dioxide. AB - A recently developed technique combining urea gel electrophoresis with Western immunoblotting has been modified for assessing the relative ability of each iron binding site of rabbit transferrin in delivering iron to rabbit reticulocytes. The two sites can be made to release iron at the same or differing rates, depending on the experimental conditions. In Hanks' balanced salts solution in an atmosphere of room air or 5% CO2, the acid-labile site in the N-terminal lobe of the protein was found to be 1.4- and 2.9-times more effective than its acid stable counterpart in providing iron to reticulocytes after 90 min incubation. Both sequential and simultaneous release of iron from the two sites was observed, but sequential release was initiated only from the N-terminal site. The same site also proved to be a better iron donor by a factor of 2 when incubations were conducted in Hanks' medium enriched with 20% serum in 5% CO2. Only in 20% serum in air were the two sites found to be equivalent iron suppliers to reticulocytes. In the cases studied, an atmosphere of 5% CO2 increased 2-fold the effectiveness of iron donation by the acid-labile site to reticulocytes, while the presence of 20% serum enhanced the iron-donating ability of the acid-stable C-terminal site. Thus, the transferrin-reticulocyte interaction is sensitive to environmental variables, and such sensitivity may help account for apparent discrepancies in previous studies of the relative iron-donating abilities of the two sites of transferrin. PMID- 2108729 TI - Two distinct light regulated G-proteins in octopus photoreceptors. AB - Two distinct light-regulated G-proteins were found in octopus photoreceptors. Gip, a 41 kDa protein from washed microvilli, was ADP ribosylated by pertussis toxin in the presence of GDP in the dark. Light and GTP analogues were inhibitory as with transducin (Gt; G-protein in vertebrate photoreceptors). G34, a 34 kDa protein from fresh octopus retina, was ADP ribosylated by both cholera and pertussis toxin in the dark. Light inhibited labeling of the 34 kDa protein by both toxins. Unlike Gip, G34 is soluble and is very labile to heat, freezing and thawing. Prolonged incubation of octopus retina with cholera toxin and labeled NAD produced an additional radioactive band at 46 kDa. Labeling of the 46 kDa protein, Gsp, was greatly enhanced by GTP analogues, but inhibited by a GDP analogue as with Gs in hormone-sensitive adenylate cyclase. In contrast to Gip and G34, labeling of the 46 kDa protein (Gsp) was not influenced by light. The two distinct light-regulated G-proteins, Gip and G34, found in octopus photoreceptors might be involved in either phototransduction or photoadaptation. The function of Gsp is not known. PMID- 2108731 TI - Competitive inhibition by glucose of myo-inositol incorporation into cultured porcine aortic endothelial cells. AB - To explore the significance of hyperglycaemia as a causal factor for the appearance of diabetic angiopathies we investigated aspects of myo-inositol metabolism in porcine aortic endothelial cells. myo-Inositol was shown to be a long-living metabolite. Its uptake into the cells was mediated by a high affinity, Na(+)-dependent uptake system inhibitable by ouabain with an apparent KM of 18.6 mumols/l, which was responsible for more than 80% of total uptake at physiological myo-inositol concentrations. Inhibition of inositol uptake by D glucose was exclusively competitive with an apparent Ki of 24 mmol/l as shown by Lineweaver-Burk- and Dixon-plot analysis. The specificity of competitive inhibition was studied. L-Glucose which is stereochemically related to myo inositol in the same way as the D-isomer proved to be an equally potent inhibitor. The hexoses D-galactose, D-mannose and D-fructose inhibited myo inositol uptake to a minor extent. D-allose and 3-O-methyl-D-glucose had no inhibitory effect indicating that the OH-group of the carbon atom in 3 position is essential for the interaction with the carrier. The acyclic hexitol sorbitol also did not compete. As expected, the aldose reductase blocker sorbinil did not influence the carrier since there is no polyol pathway operating in porcine aortic endothelial cells. In accordance with the results of the uptake experiments, the incorporation of exogenous myo-inositol into membrane phosphatidylinositol was reduced at elevated extracellular glucose levels. The results raise the possibility that hyperglycaemia impairs endothelial inositol supply. PMID- 2108732 TI - DDAVP-induced release of von Willebrand factor from endothelial cells in vitro: the effect of plasma and blood cells. AB - The vasopressin analogue 1-deamino-8-D-arginine vasopressin (DDAVP) causes an immediate, transient rise in plasma levels of von Willebrand factor (vWF) after its administration. Although it is recognized that vascular endothelial cells play an essential role in this process, the molecular basis of the response is not understood. We have investigated the phenomenon using human umbilical vein endothelial cells as an in vitro model. When normal individuals were stimulated with DDAVP, plasma from blood samples collected subsequently caused the release of vWF from cultured endothelial cells over a 24 h period (22-46% increase over baseline), compared to control plasma (5-17%). DDAVP added directly to the endothelial cells produced no increase in vWF release. When whole blood was treated in vitro with DDAVP, and the plasma subsequently added to endothelial cells, a significant increase in vWF secretion was found. Peripheral blood mononuclear cells were then tested. In the presence of DDAVP, an increased response occurred. Further fractionation of these cells showed that monocytes were largely responsible, causing an increased vWF release of 162% at 2 h. These observations were reinforced by finding that the supernatants of monocytes incubated with DDAVP were also effective in causing increased vWF release (118% compared to 58% for the control sample). Our studies suggest that DDAVP plays an indirect role in causing the release of vWF from endothelial cells, and that peripheral blood monocytes may act as intermediary target cells, which then produce factor(s) acting directly on endothelial cells. PMID- 2108733 TI - Heat-shock proteins and nucleolar hypertrophy in the liver of rat infused with methionine-free total parenteral nutrition. AB - Infusing a methionine-free solution into rats for 7 days resulted in a marked enlargement of liver nucleoli. By the analysis of two-dimensional gel electrophoresis, a spot 'a' (76 kDa, pI 5.3) stained with Coomassie blue was observed to accumulate highly in liver cytosol from rat infused with methionine free solution. Metabolically labeling experiments with [35S]methionine showed that 'a' was more heavily labeled in primary hepatocytes of rats infused with methionine-free solution than in those of control rat. To ascertain whether 'a' is one of stress proteins, primary hepatocyte cultures were incubated at 42 degrees C for 2 h. 'a' (76 kDa, pI 5.3) was slightly induced in control hepatocytes but not appreciably in hepatocytes from the treated rat. In contrast, two other spots 'b' (74 kDa, pI 5.6) and 'c' (74 kDa, pI 5.3) were highly induced at 42 degrees C in hepatocytes from control and treated rats. The antibody against the consensus sequence peptide of hsp70 family reacted with 'a' (76 kDa, pI 5.3) as well as 'b' and 'c'. Immunoblot analysis revealed that 'a' accumulates highly in hepatocytes of treated rats. These results indicate that infusion of methionine-free solution into rats induces one member of the hsp70 family in hepatocytes. PMID- 2108734 TI - Metabolism of intravenous phenylalanine by babies born before 33 weeks of gestation. AB - Random urine samples collected weekly from 22 infants of 25-32 weeks of gestation were analyzed by capillary gas chromatography-mass spectrometry to define the normal organic acid profile. Increased excretion of phenolic acid derivatives of phenylalanine and tyrosine was found in 21 samples from 13 babies during established parenteral nutrition. Compared with 53 samples collected during milk feeding, phenyllactic acid, 4-hydroxy-3-methoxyphenyllactic acid, and N acetyltyrosine were excreted significantly more often and 4-hydroxyphenyllactic and 4-hydroxyphenylpyruvic acids at significantly higher concentrations. The mean daily intake of phenylalanine (197 mg/kg) was significantly higher and that of tyrosine (22 mg/kg) significantly lower during parenteral nutrition. Three cyclohexanediol isomers were identified which might have derived from phenylalanine or one of its metabolites. PMID- 2108735 TI - Effect on the fetus of infusing a commercial amino acid preparation into a pregnant sheep. AB - The common clinical practice of intravenous feeding of the pregnant woman poses the question of the effect on the fetus of such infusions. We have used the sheep as a model to study the change in fetal amino acid levels after a maternal infusion of Synthamin 13. The maternal plasma aminogram largely reflects the amino acid pattern in the infusate. However, in the fetal circulation only the branched chain amino acids (leucine, isoleucine and valine), phenylalanine and alanine rose significantly after infusion. Only leucine and isoleucine were observed to spill into the fetal urine. The results suggest that the ovine placenta selectively modifies the amino acid profile presented to the fetus when the maternal plasma aminogram is distorted. However, the fetus is not totally protected from changes in phenylalanine, which in high concentrations, is detrimental to normal development. PMID- 2108736 TI - Absorption and disposition kinetics of chlorothiazide in protein-calorie malnutrition. AB - The influence of dietary protein deficiency on the absorption and disposition kinetics of chlorothiazide was investigated in male Sprague-Dawley rats fed for 4 weeks on a 23 per cent (control) or a 5 per cent (low) protein diet ad libitum. Chlorothiazide in plasma and urine was determined by a sensitive and specific HPLC assay. Following an intravenous dose of 10 mg kg-1 chlorothiazide, there was a significant decrease in the total plasma clearance (Cl) per kg of body weight from 1.80 +/- 0.15 to 1.29 +/- 0.15 l h-1 kg-1 and apparent steady-state volume of distribution from 0.65 +/- 0.13 to 0.38 +/- 0.07 l kg-1 in the protein deficient rats. However, no significant difference was found in the two groups of animals with respect to mean residence time (MRT) and free fraction of drug in plasma. The mean harmonic half-life was increased from 72 to 91 min in the protein-deficient rats. The urinary recovery of unchanged chlorothiazide in 48 h was essentially complete in both groups of animals. The absorption of chlorothiazide, as assessed by the mean urinary recovery of unchanged drug after oral administration, was 66 per cent and 68 per cent in normal and protein deficient rats, respectively. PMID- 2108737 TI - Distribution of phototrophic microbes in the flat laminated microbial mat at Laguna Figueroa, Baja California, Mexico. AB - The microbial mat community in the saltmarsh/evaporate flat interface at Laguna Figueroa involved in the deposition of laminated sediments was investigated. Pigment analysis, light microscopy and transmission electron microscopy were used to determine the relative abundance and distribution of phototrophic species. The community is vertically stratified into four distinct phototrophic populations. The layering could be distinguished by pigment and species composition. The two layers closest to the surface contained mostly oxygenic phototrophs and chlorophyll a as the primary photosynthetic pigment. Anoxic phototrophs predominated in the bottom two layers with bacteriochlorophylls a and c in the third layer and bacteriochlorophyll a and b in the bottom layer. The surface yellow layer was composed primarily of Navicula, Rhopalodia and other diatom species as well as the cyanobacteria Aphanothece sp. and Phormidium sp. Microcoleus chthonoplasces and Chroococcidiopsis sp. were the major cyanobacteria in the green colored second layer. In the third layer, pinkish-purple in color, purple photographs (Chromatium sp., Thiocapsa roseoparsicina) and filamentous green phototrophs (Chloroflexus sp., Oscillochloris sp.) were abundant. The fourth and deepest photosynthetic layer was salmon colored and composed primarily of Thiocapsa pfennigii, and other purple sulfur phototrophs. The pattern of alternating light (oxygenic community) and dark (anoxygenic community) layering preserved in older laminae is a consequence of this community structure. Study of the flat laminated mat over the 10-year period (1978-1988) including and after its destruction by catastrophic flooding events in 1978 and 1980, showed a succession of stratified communities culminating in the return of Microcoleus and the full compliment of layers by the fall of 1984. PMID- 2108738 TI - The haematological manifestations of acquired immune deficiency syndrome. PMID- 2108739 TI - HIV-1 infection in haemophilia. AB - Guidelines have been prepared by the National Hemophilia Foundation, USA, for treating patients with haemophilia, these are: 1. General recommendations. The risks of withholding treatment far outweigh risks of treatment. Patients should however be educated to use appropriate clotting factor doses to minimize overuse and contain costs. 2. Factor VIIIC-deficient patients. DDAVP should be used whenever possible by patients with mild or moderate factor VIIIC deficiency. When feasible, an alternative to concentrates may be the use of cryo-precipitate prepared from one well-screened donor or from a small number of such donors. (a) Prevention of hepatitis. Hepatitis B vaccination is essential for uninfected patients. Preliminary data suggest that products that are pasteurized, solvent/detergent-treated or monoclonal antibody-purified are at a reduced risk of transmitting hepatitis viruses. (b) Prevention of HIV-1. Concentrates pasteurized, treated with solvent/detergent, purified with monoclonal antibody, heated in suspension with organic solvents, or dry heat-treated for long periods are preferred. These products carry a substantially reduced risk of transmitting HIV-1. 3. Factor IX deficiency. For patients with severe deficiency the use of virus-inactivated Factor IX concentrate is recommended. For mild to moderate patients when feasible an alternative would be fresh, frozen plasma prepared from one well-screened and repeatedly-tested donor or from a small number of such donors. In the past few years, significant progress has been made in understanding the nature of the defect in haemophilia both at the molecular and structural levels, such a foundation is necessary for definitive treatments in the future. For now, however, the dark side of replacement therapy must be accepted along with its benefits. PMID- 2108740 TI - Reversal of phenol and naphthalene effects on ciliate chemoattraction. PMID- 2108741 TI - Immunity of PCB transplacental Yu-Cheng children in Taiwan. PMID- 2108742 TI - Effectiveness of Pseudomonas aeruginosa for detoxification of tetramethylthiuram disulfide (TMTD) from contaminated soil. PMID- 2108743 TI - Effect of gamma irradiation on a PCB mixture in organic solvent. PMID- 2108744 TI - Organochlorine residues in adipose tissue of chamois from the Catalan Pyrenees, Spain. PMID- 2108745 TI - A new approach for the analysis of HLA class II polymorphism: 'HLA oligotyping'. AB - Histocompatibility typing allows the matching of patients and donors in organ transplantation, and the accuracy of HLA matching influences to a great extent the clinical outcome. Recent breakthroughs in the molecular biology of HLA class II genes have revealed that the degree of HLA diversity and polymorphism is in fact much greater than was expected on the basis of the traditional serological HLA typing assays. In parallel, it has become possible to analyse this extensive polymorphism directly at the level of the HLA class II genes and of their DNA sequences. We have described a DNA typing procedure referred to as 'HLA oligotyping' which is based on the hybridisation of allele and loci specific oligonucleotide probes. This procedure has now become operational on a large scale and this review describes the principles and major applications of the technique. It consists in the hybridisation of DNA with informative sequence specific oligonucleotide probes, following an amplification of DNA in vitro by the polymerase chain reaction (PCR). The use of this highly sensitive technique for HLA-DR, -DQ and -DP typing is discussed, focusing on the clinical applications in the field of organ transplantation, particularly for bone marrow transplantation with unrelated donors. It now allows the unambiguous identification of all HLA subtypes, including those that cannot be recognised otherwise, and it represents powerful complement to current methods of HLA typing. Finally this methodology is widely used in HLA-disease association studies, aiming at the characterisation of HLA class II epitopes involved in the susceptibility or resistance to autoimmune diseases. PMID- 2108746 TI - Calcium sensitisers. PMID- 2108747 TI - Surgery and salmonella. PMID- 2108748 TI - Care for the infirm elderly. PMID- 2108749 TI - Prevalence of vertebral compression fractures due to osteoporosis in ankylosing spondylitis. AB - OBJECTIVE: To determine the prevalence of vertebral compression fractures due to osteoporosis in patients with ankylosing spondylitis. DESIGN: Prospective study of 111 consecutive patients; patients with vertebral compression fractures were entered into a case-control study. SETTING: Outpatient clinic at the centre for rheumatic diseases, Glasgow. PATIENTS: 111 Consecutive patients with ankylosing spondylitis. Patients with compression fractures were matched for age and sex with two controls selected from the rest of the group. Patients with biconcave vertebral fractures were also studied. MAIN OUTCOME MEASURES: Assessments of spinal deformity and mobility and analysis of lateral radiographs of spines for presence of syndesmophytes. RESULTS: Fifteen patients with compression fractures and five with biconcave fractures were studied. Compared with the controls the patients with compression fractures had increased formation of syndesmophytes in the lumbar spine, whereas those with biconcave fractures had increased formation throughout the spine. Patients with compression fractures also had a greater degree of spinal deformity (distance from wall to tragus 24.5 cm v 12.7 cm in controls), less spinal mobility (20 v 45.6 degrees of flexion), and reduced chest expansion (2 cm v 3cm). CONCLUSION: Vertebral compression fractures due to osteoporosis are a common but frequently unrecognised complication of ankylosing spondylitis and may contribute to the pathogenesis of spinal deformity and back pain. PMID- 2108750 TI - Coffee consumption and death from coronary heart disease in middle aged Norwegian men and women. AB - OBJECTIVE: To study the association between number of cups of coffee consumed per day and coronary death when taking other major coronary risk factors into account. DESIGN: Men and women attending screening and followed up for a mean of 6.4 years. SETTING: Cardiovascular survey performed by ambulatory teams from the National Health Screening Service in Norway. PARTICIPANTS: All middle aged people in three counties: 19,398 men and 19,166 women aged 35-54 years who reported neither cardiovascular disease or diabetes nor symptoms of angina pectoris or intermittent claudication. MAIN OUTCOME MEASURE: Predictive value of number of cups of coffee consumed per day. RESULTS: At initial screening total serum cholesterol concentration, high density lipoprotein cholesterol concentration, blood pressure, height, and weight were measured and self reported information about smoking history, physical activity, and coffee drinking habits was recorded. Altogether 168 men and 16 women died of coronary heart disease during follow up. Mean cholesterol concentrations for men and women were almost identical and increased from the lowest to highest coffee consumption group (13.1% and 10.9% respectively). With the proportional hazards model and adjustment for age, total serum and high density lipoprotein cholesterol concentrations, systolic blood pressure, and number of cigarettes per day the coefficient for coffee corresponded to a relative risk between nine or more cups of coffee and less than one cup of 2.2 (95% confidence interval 1.1 to 4.5) for men and 5.1 (0.4 to 60.3) for women. For men the relative risk varied among the three counties. CONCLUSIONS: Coffee may affect mortality from coronary heart disease over and above its effect in raising cholesterol concentrations. PMID- 2108751 TI - Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving haemodialysis. Canadian Erythropoietin Study Group. AB - OBJECTIVE: To determine whether recombinant human erythropoietin improves the quality of life and exercise capacity of anaemic patients receiving haemodialysis. DESIGN: A double blind, randomised, placebo controlled study. SETTING: Eight Canadian university haemodialysis centres. PATIENTS: 118 Patients receiving haemodialysis aged 18-75 with haemoglobin concentrations less than 90 g/l, no causes of anaemia other than erythropoietin deficiency, and no other serious diseases. INTERVENTIONS: Patients were randomised to three groups to receive placebo (n = 40), erythropoietin to achieve a haemoglobin concentration of 95-110 g/l (n = 40), or erythropoietin to achieve a haemoglobin concentration of 115-130 g/l (n = 38). Erythropoietin was given intravenously thrice weekly, initially at 100 units/kg/dose. The dose was subsequently adjusted to achieve the target haemoglobin concentration. All patients with a serum ferritin concentration less than 250 micrograms/l received oral or intravenous iron for one month before the study and as necessary throughout the trial. MAIN OUTCOME MEASURES: Scores obtained with kidney disease questionnaire, sickness impact profile, and time trade off technique; and results of six minute walk test and modified Naughton stress test. RESULTS: The mean (SD) haemoglobin concentration at six months was 74 (12) g/l in patients given placebo, 102 (10) g/l in those in the low erythropoietin group, and 117 (17) g/l in those in the high erythropoietin group. Compared with the placebo group, patients treated with erythropoietin had a significant improvement in their scores for fatigue, physical symptoms, relationships, and depression on the kidney disease questionnaire and in the global and physical scores on the sickness impact profile. The distance walked in the stress test increased in the group treated with erythropoietin, but there was no improvement in the six minute walk test, psychosocial scores on the sickness impact profile, or time trade off scores. There was no significant difference in the improvement in quality of life or exercise capacity between the two groups taking erythropoietin. Patients taking erythropoietin had a significantly increased diastolic blood pressure despite an increase in either the dose or number of antihypertensive drugs used. Eleven of 78 patients treated with erythropoietin had their sites of access clotted compared with only one of 40 patients given placebo. CONCLUSIONS: Patients receiving erythropoietin were appreciably less fatigued, complained of less severe physical symptoms, and had moderate improvements in exercise tolerance and depression compared with patients not receiving erythropoietin. At the doses used in this trial there was a higher incidence of hypertension and clotting of the vascular access in patients treated with erythropoietin. PMID- 2108752 TI - Short term increase in risk of breast cancer associated with full term pregnancy. PMID- 2108753 TI - Proliferative retinopathy and nephropathy at presentation in young insulin dependent diabetics. PMID- 2108754 TI - Childhood leukaemia around the La Hague nuclear waste reprocessing plant. PMID- 2108755 TI - Effectiveness of using end tidal carbon dioxide concentration to monitor cardiopulmonary resuscitation. PMID- 2108756 TI - Diagnosis and antibiotic treatment of acute otitis media: report from International Primary Care Network. AB - STUDY OBJECTIVE: The relation between a history of disorders suggestive of acute otitis media, symptoms, and findings of an examination of the tympanic membrane and doctors' certainty of diagnosis. Also, to examine differences in prescribing habits for acute otitis media among doctors from different countries. DESIGN: Questionnaires were completed by participating doctors for a maximum of 15 consecutive patients presenting with presumed acute otitis media. SETTING: General practices in Australia, Belgium, Great Britain, Israel, The Netherlands, New Zealand, Canada, Switzerland, and the United States. PATIENTS: 3660 Children divided into the three age groups 0-12 months, 13-30 months, and greater than or equal to 31 months. MAIN OUTCOME MEASURES: General practitioners' responses to questions on their diagnostic certainty and resolution of patients' symptoms after two months. RESULTS: The diagnostic certainty in patients aged 0-12 months was 58.0%. This increased to 66.0% in those aged 13-30 months and 73.3% in those aged greater than or equal to 31 months. In all age groups diagnostic certainty was positively associated with the finding of a tympanic membrane that was discharging pus or bulging. Redness of the membrane and pain were also associated with certainty in patients aged 13-30 months, and a history of decreased hearing or recent upper respiratory infection was positively associated in patients aged greater than or equal to 31 months. The proportion of patients prescribed antibiotics varied greatly among the countries, from 31.2% in The Netherlands to 98.2% in both Australia and New Zealand, as did the duration of treatment. Patients who did not take antibiotics had a higher rate of recovery than those who did; the rate of recovery did not differ between different types of antibiotic. CONCLUSIONS: Doctors' certainty of diagnosis of acute otitis media was linked to patient's age. Improved criteria or techniques for diagnosing acute otitis media, especially in very young children, need to be developed. Antibiotic treatment did not improve the rate of recovery of patients in this study. PMID- 2108757 TI - Creating a new drug service in Edinburgh. AB - After one year Edinburgh's Community Drug Problem Service has shown that if psychiatric services offer consultation and regular support for drug users many general practitioners will share the care of such patients and prescribe for them, under contract conditions, whether the key worker is a community psychiatric nurse or a drug worker from a voluntary agency. This seems to apply whether the prescribing is part of a "harm reduction" strategy over a long period or whether it is a short period of methadone substitution treatment. Given the 50% prevalence of HIV infection among drug users in the Edinburgh area and the fact that only half of them have been tested for seropositivity, the health and care of this demanding group of young people with a chaotic lifestyle are better shared among primary care, community based drug workers, and specialist community drugs team than treated exclusively by a centralised hospital drug dependency unit. As the progression to AIDS is predictable in a larger proportion of drug users who are positive for HIV, there is an even greater need for coordinated care between specialists and community agencies in the near future. PMID- 2108758 TI - Portal vein thrombosis in myeloproliferative disease. Uses of thrombolytic and antiplatelet treatment. PMID- 2108759 TI - Gall stones. PMID- 2108760 TI - Toddlers, teapots, and kettles: beware intraoral scalds. PMID- 2108761 TI - ABC of transfusion. Red cell substitutes. PMID- 2108762 TI - Should fertile people have access to in vitro fertilisation? PMID- 2108763 TI - Research ethics committees. PMID- 2108764 TI - What is medically pointless? PMID- 2108765 TI - Patients' right to know. PMID- 2108766 TI - Impotence after prostatectomy. PMID- 2108767 TI - Scuba divers with asthma. PMID- 2108768 TI - Should radiologists talk to patients? PMID- 2108769 TI - Variations in reported serum alkaline phosphatase activities. PMID- 2108770 TI - Why are the Japanese living longer? PMID- 2108771 TI - Nibblers, gorgers, snackers, and grazers. PMID- 2108772 TI - Districts' use of thrombolytic agents. PMID- 2108773 TI - Crisis in our hospital kitchens. PMID- 2108774 TI - Geographic variations in blood pressure. PMID- 2108775 TI - Lymphomatoid granulomatosis. PMID- 2108776 TI - Node negative breast cancer. PMID- 2108777 TI - Quinine induced granulomatous hepatitis and vasculitis. PMID- 2108778 TI - Acute dystonia induced by midazolam and abolished by flumazenil. PMID- 2108779 TI - Clinical signs of amyotrophic lateral sclerosis developing after polyradiculoneuropathy associated with amitriptyline. PMID- 2108780 TI - Hypertensive crisis precipitated by a monoamine oxidase inhibitor in a patient with phaeochromocytoma. PMID- 2108781 TI - ABC of transfusion. Plasma, plasma products, and indications for their use. PMID- 2108782 TI - The effect of nabumetone and its principal active metabolite on in vitro human gastric mucosal prostanoid synthesis and platelet function. AB - Nabumetone is a novel non-steroidal anti-inflammatory drug (NSAID) which although a weak cyclooxygenase inhibitor is converted by the liver to metabolites which are more potent inhibitors of cyclooxygenase. Nabumetone may thus avoid the occurrence of gastric erosion while maintaining its efficacy as an anti inflammatory drug. We compared the effects of nabumetone and 6-methoxy-2 naphthylacetic acid (6MNA; the principal metabolite of nabumetone) with naproxen and indomethacin on in vitro synthesis of the gastroprotective prostaglandins I2 and E2 by human gastric mucosa. To study the effects of 6MNA on peripheral target tissues the effects of the above NSAIDs on human platelet aggregation and thromboxane A2 synthesis were also studied. Prostanoid synthesis by the human gastric mucosa was inhibited by indomethacin, naproxen and 6MNA (in this order of potency) whereas nabumetone was completely without effect. Platelet aggregation and thromboxane A2 synthesis were similarly inhibited by the NSAIDS (viz. indomethacin greater than naproxen greater than 6MNA greater than nabumetone). These results support the view that nabumetone does not inhibit gastroprotective prostanoid synthesis, whereas its active metabolite 6MNA is an effective inhibitor of prostanoid synthesis in target tissues. PMID- 2108783 TI - NSAID-associated gastropathy--a role for misoprostol? PMID- 2108784 TI - Metabolic effects of cancer. AB - The potential causes of deranged metabolism in cancer are discussed with emphasis on changes in energy metabolism of glucose, fat and protein. The implications of these changes for the treatment of cachexia are then considered. PMID- 2108785 TI - Excitatory effects of thyrotropin-releasing hormone (TRH) in hypoglossal motoneurons. AB - The effect of thyrotropin-releasing hormone (TRH) was studied in 30 hypoglossal motoneurons from brainstem slices of guinea pigs. Bath application of TRH resulted in an increase of the spontaneous excitatory synaptic activity, depolarization of the neurons, increase of the input resistance and change of the duration of the falling phase of excitatory postsynaptic potentials. The depolarizing response and membrane conductance change was the result of a direct postsynaptic action of TRH, possibly mediated by a reduction of a potassium conductance. PMID- 2108786 TI - Bromocriptine-induced rotation: characterization using a striatal efferent lesion in the mouse. AB - Two lesion techniques were used to elucidate the mode of action of bromocriptine (BRC)-induced behavior in mice. With the first lesion, a unilateral 6 hydroxydopamine (6-OHDA) preparation, BRC administration resulted in contralateral rotation which was blocked by alpha-methyl-para-tyrosine (AMPT), comparable to previous reports using rats. After striatonigral/entopeduncular lesion, mice did not rotate in response to doses of BRC up to 30 mg/kg but did show general activation which was also inhibited by AMPT pretreatment. It is concluded that BRC does not elicit rotation when there is no dopaminergic asymmetry such as that caused by a unilateral 6-OHDA lesion or no asymmetry in the striatonigral or striatoentopeduncular efferents. Since BRC-induced behaviors are dependent on intact presynaptic dopamine and BRC is predominantly a D-2 agonist, behaviors elicited in response to BRC must be the result of coactivation of D-1 receptors by endogenous dopamine. Thus, the behavioral effects of BRC, and perhaps D-2 agonists in general, must be mediated by efferents other than the striatonigral and striatoentopeduncular pathways. PMID- 2108787 TI - [Reversible cardiorespiratory failure induced by CO2 inhalation in cats]. AB - Experiments on anesthetized cats showed that short-term inhalation of concentrated CO2 induced reversible asphyxia resulting in acute cardiorespiratory failure. The stage of hyperventilation was followed by apnea initially interrupted by primary gasps and by bradycardia and drop in systemic blood pressure. After termination of CO2 supply in the state of apnea or after onset of resuscitation the blood pressure started to increase, secondary gasps appeared and regular respiration was gradually restored. The rate and duration of gasps decreased but the inspiratory force and the achieved tidal volume and airflow were greater than at normal respiration. During reversible asphyxia induced by CO2 inhalation the ECG exhibited invariably severe arrhythmias, most frequently atrioventricular block of different degrees. Bilateral cervical vagotomy failed to prevent the occurrence of ECG changes. After administration of Indral, however, arrhythmias were recorded only exceptionally. PMID- 2108788 TI - [Effects of the deafferentation of the pineal gland by bilateral ablation of superior cervical sympathetic ganglia on the autumnal recrudescence of testicular activity in mink]. AB - The effects of deafferentation of the pineal gland on the autumnal recrudescence of testicular activity in mink raised in a natural photoperiod were studied following bilateral superior cervical ganglionectomy. Animals were operated at four different times between the end of summer and the end of autumn, i.e., when daylength at this latitude naturally decreases from 12.5 to 8.5 hrs. Deafferentation of the pineal gland on September 15 (daylength 12.5 hrs.) or October 20 (daylength 10.5 hrs.), when testis volume and plasma testosterone are normally reduced to a minimum, caused these values to remain at the same low levels during the whole observation period. In contrast deafferentation on October 28 (daylength 10 hrs.), did not present the recrudescence of testicular activity, but the rise was transitory and testis development was incomplete. Finally, when the operation was performed on December 1, during the phase of natural sexual resumption, the increases in testicular volume and plasma testosterone were not affected at all and the profiles of their subsequent variations conformed to the patterns of intact animals. PMID- 2108789 TI - Maintenance of compaction and adherent-type junctions in mouse morula-stage embryos. AB - Timed morulae of different stages of development were exposed to cytochalasin B causing depolymerisation of microfilaments and to ECCD-1 antibodies interacting with Ca2(+)-dependent adhesion molecules or cultured in the absence of calcium. All three treatments decompacted mid-morula-stage embryos within one hour. Late morulae were resistant to ECCD-1 antibody treatment and relatively resistant to calcium-free cultivation, but not to cytochalasin B treatment. Scanning electron microscopy revealed that the decompacting treatments not only loosened the interblastomere contacts but also resulted in rearrangement of the cell surface microvilli. Transmission electron microscopy showed that normal, untreated embryos had specialized membrane junctions in the most apical regions of the interblastomere contacts. Immunoelectron microscopy revealed that these apical junction areas contained vinculin, a protein typical of adherent junctions. Upon decompaction the apical junctions disappeared completely. When transferred back to the normal medium, the embryos rapidly started to recompact. Simultaneously the apical junctions and cell surface microvilli reassumed the organization characteristic of the morula stage. Late morulae that were resistant to treatment had normal apical junctional areas. During subcultivation in the normal medium, the treated morulae developed into morphologically normal blastocysts. These data indicate that adherent-type junctions and cell surface microvilli participate in the initiation and maintenance of compaction of morula-stage embryos. PMID- 2108790 TI - Bone diminution of osteoporotic females at different skeletal sites. AB - The bone mineral density (BMD) of the radius and spine was determined by photo absorptiometry in a large number of controls (radius: n = 111; spine: n = 85; age range: 50-79 years) and osteoporotic women (radius: n = 98; spine n = 140; age range: 50-79 years) with at least one "atraumatic" vertebral compression fracture. Compared to age-matched controls, the BMD of the osteoporotic women showed the following diminutions: sixth decade: radius: -9.1%; spine: -25%; femur: -33%; seventh decade: radius: -16%; spine: -19%; femur: -23%; eighth decade: radius: -21%; spine: -20%; femur: -24%. The BMD was significantly diminished at all sites in all decades but in contrast to the radius, the difference from controls was bigger in the spine and femur in the sixth decade than in the seventh and eighth decade. In the osteoporotic women there was a significant correlation between radius BMD and age (r = -0.56; P less than 0.01) but not between spine or femoral BMD and age. The femoral neck BMD was also determined in a subset group of female controls (n = 68), patients with crush fractures of the spine without a fracture of the hip (n = 46), and in patients with fractures of the proximal femur (n = 21). There was no difference among these groups in mean age (64 +/- 7, range: 50-79 years). Patients with hip fracture and spine fracture showed bone diminution in all three regions that was significantly below controls (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108791 TI - Calcitonin and bone mass status in congenital hypothyroidism. AB - Calcitonin (CT) deficiency and its possible repercussions on bone mass were studied in a group of 9 adult patients (7 females, 2 males) with congenital hypothyroidism of dysgenetic origin. Using a new extraction method (exCT) which considerably improves the sensitivity and the specificity of the assay for CT monomer, we measured CT levels before and after a short calcium (Ca) stimulation test (2 mg Ca/kg over 5 minutes) to evaluate C-cell secretory reserve. Mean basal plasma CT concentrations were lower in the hypothyroid women (mean +/- SEM: 0.6 +/- 0.1 pg/ml) than in 30 normal female controls (1.7 +/- 0.2 pg/ml, P less than 0.001). Serum calcium increased similarly in the two groups, but postinfusion CT levels were lower in the hypothyroid women, (1.7 +/- 0.2 pg/ml) than in normal women (16.8 +/- 2.9 pg/ml), P less than 0.001. Hypothyroid women showed a 10% reduction in bone mineral content at the diaphyseal site in the radius, 0.840 +/- 0.037 g/cm, compared with normal age-matched controls, 0.930 +/- 0.020 g/cm, (P less than 0.05). Our study demonstrates the existence of a profound CT-monomer deficiency in adult patients with thyroid agenesis or dysgenesis. Both calcitonin deficiency and thyroid hormone treatment could play a role in the observed bone loss. Attention should therefore be paid to bone metabolism during treatment of congenital hypothyroidism to avoid further bone loss. PMID- 2108792 TI - Heterogeneity of pseudohypoparathyroidism type I from the aspect of urinary excretion of calcium and serum levels of parathyroid hormone. AB - Urinary excretion of calcium (Ca) was measured in 9 patients with pseudohypoparathyroidism (PHP) type I--3 with Albright's hereditary osteodystrophy (AHO): AHO(+) and 6 without AHO: AHO(-)--and in 13 with idiopathic hypoparathyroidism (IHP), treated with active vitamin D3 (1,25(OH)2D3 or 1 alpha OHD3) to maintain serum Ca levels at 8.4-9.5 mg/dl. Fasting urinary excretion of Ca in PHP was significantly lower than that in IHP. Moreover, fasting urinary excretion of Ca in PHP AHO(+) was lower than that in PHP AHO(-). This difference was also seen in the urine after oral loading of Ca. Urinary excretion of sodium (Na) was not different between PHP AHO(+) and PHP AHO(-). Serum levels of immunoreactive PTH in PHP AHO(+) were higher than those in PHP AHO(-). The difference in urinary excretion of Ca between PHP AHO(+) and PHP AHO(-) may come from the difference in the circulating levels of PTH. PMID- 2108793 TI - Comparison of the effects of amino-terminal synthetic parathyroid hormone-related peptide (PTHrP) of malignancy and parathyroid hormone on resorption of cultured fetal rat long bones. AB - We have compared the effects of of various synthetic amino-terminal forms of human parathyroid hormone-related peptide (PTHrP) of malignancy with synthetic parathyroid hormone (PTH) on the resorptive responses of fetal rat long bones in organ culture. PTH and PTHrP increased 45Ca release at concentrations of 0.1-25 nM. PTHrP (1-40) and bovine PTH (1-34) were more potent than human PTH (1-34) and PTHrP (1-34). However, the slopes of the dose-response curves and the maximal resorptive effects were similar. There was a marked decrease in the potency of amino-terminal PTHrP peptides as the length was decreased. PTHrP (1-29) and PTHrP (1-25) were inactive at 120 nM. Further comparison of bPTH (1-34) and PTHrP (1 34) showed that both could induce bone resorption after a brief (6 hours) exposure and that the response to PTHrP (1-34) was qualitatively similar to that of bPTH (1-34) with respect to enhancement by ACTH and inhibition by calcitonin and glucocorticoids. Hydroxyurea and indomethacin did not block the resorptive response to either agonist. Cyclic AMP production in response to PTHrP (1-34) and (1-40) was similar to that for bPTH (1-34) in ROS 17/2.8 cells. The cyclic AMP (cAMP) response was much smaller in fetal rat long bones and calvariae, and bPTH was more potent than PTHrP. These studies confirm that PTHrP is quantitatively similar in its effects on bone resorption to PTH and are consistent with the two agents acting on the same receptor. PMID- 2108794 TI - Electron microscopy of developing calvaria reveals images that suggest that osteoclasts engulf and destroy osteocytes during bone resorption. AB - It is generally accepted that osteoclasts are responsible for the breakdown and removal of bone matrix constituents. However, very little is known about the fate of osteocytes during bone resorption. In the present study we have examined sites of bone destruction in calvaria of young rats aged 4-9 days in the hope of obtaining information on the fate of osteocytes. Decalcified glutaraldehyde formaldehyde-fixed specimens were prepared for ultrathin section electron microscopy. When sequentially arranged, the images obtained suggest that osteoclasts engulf and destroy osteocytes during bone degradation. We propose that the following sequence of events takes place when a lacuna is opened up by an osteoclast: (1) When the osteoclast comes in contact with an osteocyte, the villi of the ruffled border become flat and broad. (2) Long osteoclastic extensions surround the osteocyte. (3) The osteocyte is subsequently internalized with apparent degradation. PMID- 2108795 TI - Thermal decomposition of developing enamel. AB - The decomposition of forming, maturing, and mature enamel was studied between room temperature and 1,000 degrees C by powder X-ray diffraction and infrared absorption methods. In mature dental enamel, carbonate decomposition proceeds relatively fast until 500 degrees C and at a slower rate beyond it. In forming and maturing enamel, decomposition is faster and is completed around 800 degrees C. The formation of beta-Ca3(PO4)2 is observed in dental enamel at 500 degrees C. At 1,000 degrees C, the apatite phase in forming and maturing enamel transforms almost completely to beta-Ca3(PO4)2, whereas in mature enamel, even at 1,000 degrees C, only partial decomposition occurs. Infrared results show the appearance in dental enamel of (1) A-type carbonate at room temperature and in the 500-900 degrees C range, in addition to the commonly observed B-type carbonate, and (2) intermediate CO2 molecules during carbonate decomposition (200 500 degrees C). PMID- 2108796 TI - Insulin-like growth factor-I and insulin-like growth factor-II induce c-fos in mouse osteoblastic cells. AB - We investigated the expression of c-fos in mouse osteoblast-like cultures treated with insulin-like growth factor (IGF)-I and IGF-II. The IGFs are present in bone, are produced by osteoblast-like cells in culture, and stimulate osteoblast cell proliferation. Quiescent, subconfluent cultures of the clonal osteoblast-like mouse calvarial cell line, MC3T3-E1, were treated with 10 ng/ml of IGF-I or IGF II. RNA was extracted at 0, 15, 30, 60, 120 and 240 minutes, and c-fos messenger RNA (mRNA) was analyzed on Northern blots. Both IGFs transiently increased c-fos mRNA levels 25-28 fold at 15-30 min. To determine if c-fos induction was unique to the MC3T3-E1 cell line, effects of IGF-1 and IGF-II (3 ng/ml) were also tested in quiescent, serum-free primary mouse calvarial cells. Levels of c-fos mRNA were increased at 15 and 30 minutes (40-fold with IGF-I and 5-fold with IGF-II). These results indicate that IGF-I and IGF-II caused a rapid and transient induction of c-fos mRNA in murine osteoblasts. PMID- 2108797 TI - Osteoblast low-molecular-weight proteinase inhibitor. I. Isolation and characterization of activity from osteoblastic cells and bone. AB - Isolated mouse calvarial cells having phenotypic characteristics of osteoblasts, mouse parietal bone segments, mouse serum, and control mouse lung fibroblasts were extracted in NaCl and ultrafiltered to recover final concentrates having nominal molecular weights between 50,000 and 1000 daltons. Final concentrates of osteoblasts and bone but not of serum or control fibroblasts were positive for the inhibition of trypsin degradation of fibrin. Osteoblast final concentrates inhibited trypsin hydrolysis of the synthetic substrate p-tosyl-L-arginine methyl ester. Osteoblast and bone final concentrates comigrated with Trasylol but were electrophoretically distinct from alpha 1-antiproteinase. Final concentrates of osteoblast and bone extracts did not inhibit tadpole collagenase using the [3H]glycine-labeled diffuse chick collagen fibril assay. High-performance liquid chromatography (HPLC) of osteoblast final concentrates after purification using immobilized trypsin affinity chromatography revealed the presence of a major peak that was positive for the inhibition of trypsin. Molecular weight determination by HPLC indicated that the inhibitor(s) range in nominal molecular weight from 4300 to 5100 daltons. The presence of low-molecular-weight serine proteinase inhibitory activity in bone suggests its participation in the regulation of bone resorption through the regulation of enzyme activation of collagenase, and possibly its role in defense against bone matrix enzymatic degradation during tumor cell invasion. PMID- 2108798 TI - Induction of matrix Gla protein synthesis during prolonged 1,25-dihydroxyvitamin D3 treatment of osteosarcoma cells. AB - The synthesis of matrix Gla protein (MGP) and bone Gla protein (BGP) have been shown to be mutually exclusive in all osteosarcoma cell lines investigated. In the cell lines that produce the respective proteins, synthesis is stimulated by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) within the first several hours of hormone treatment. In the present studies we have investigated the effects of longer-term treatment with 1,25(OH)2D3 in the ROS 17/2 cell line, a cell line that synthesizes BGP constitutively but does not synthesize MGP. In agreement with earlier studies, the rate of BGP synthesis increases within 8 hours of hormone treatment, is maximal by 24 hours, and remains at the maximal rate through 48 hours of 1,25(OH)2D3 treatment. The present study is the first to report that the rate of BGP secretion at times beyond 48 hours declines to that of control cultures despite the continued administration of 1,25(OH)2D3, and that MGP synthesis is induced in ROS 17/2 cells by 48 hours of 1,25(OH)2D3 treatment. At this time, MGP mRNA could be detected by northern blot analysis and MGP secretion could be demonstrated by radioimmunoassay of culture medium. Both the level of MGP message per unit total RNA and the rate of MGP secretion into culture medium increased steadily between 2 and 6 days of 1,25(OH)2D3 treatment. The MGP synthesized by the 1,25(OH)2D3-treated ROS 17/2 cells was identical to that found in bone by northern blot analysis of message and by western blot analysis of the media antigen. Half-maximal induction of MGP synthesis was obtained with 0.3 nM 1,25(OH)2D3, a 60-fold higher dosage than was required for the half maximal stimulation of BGP synthesis in these cells. Treatment of ROS 17/2 cells with 24,24-F21,25(OH)2D3 suggests that the observed difference in dose dependence is not due to an increased rate of hormone catabolism. PMID- 2108799 TI - Effect of radiographic abnormalities on rate of bone loss from the spine. AB - When measured by dual-photon absorptiometry (DPA), the adjusted annual rate of change in bone mineral density (BMD) of the lumbar spine was 0.11 +/- 0.51 (SE)% in 44 healthy postmenopausal women with radiographic abnormalities in the scan field and -0.97 +/- 0.26% in 249 women with normal lateral lumbar radiographs (p = 0.046). Rates of loss of BMD from the radius were similar in the 2 groups. Spurious rates of loss of spine BMD are likely to be found in subjects with calcification of the aorta, osteophytes or other abnormalities in the spine scan field. This should be kept in mind when serial spine scans are being considered in these subjects. PMID- 2108800 TI - Simultaneous measurement of bone formation and resorption in vivo. AB - Bone resorption and formation in terms of milligram of calcium deposited into and released from whole humerus of 15-23 weeks old male rats were assessed, via linear least-squares regression analysis of change in calcium content and 3H tetracycline kinetics of the bone. The rate of resorption was 0.376 mg calcium per day, while formation was 0.758 mg calcium per day. The data indicate that the computation results in a simultaneous and explicit measurement of bone resorption and formation at the organ level. PMID- 2108801 TI - The inotropic effect of digoxin on an isolated rat heart in hypercapnia and (or) hypoxia. AB - The explanation for the increased frequency of troubles with digoxin therapy in patients with chronic pulmonary diseases is debated. The reported effects of hypoxia in vivo on myocardial levels of digoxin are contradictory, and there have been few studies on the effects of hypercapnia. In the past, it has been shown in rat myocardial tissue at rest in vitro that hypoxia decreased and hypercapnic acidosis increased the digoxin uptake. We performed a new study in vitro in an isolated beating rat heart perfused at constant flow (37 degrees C) and stimulated at a constant frequency (6 Hz). The performances were recorded with an intraventricular balloon equipped with a tip-manometer catheter. The action of digoxin was studied by recording systolic pressure (PS) and diastolic pressure (PD), the left ventricular developed pressure (LVDP = PS - PD), the (dP/dt)max, and the ratio (dP/dt)max/PS. First, the heart was perfused for 30 min with a modified Tyrode's solution perfusate aerated with carbogen (pH = 7.40; PCO2 = 37 mmHg; PO2 = 530 mmHg) (1 mmHg = 133.32 Pa). Various parameters of contractions were recorded (initial control values). Then the heart was perfused for 15 min with Tyrode's solution aerated either with a hypoxic gas mixture (pH = 7.41; PCO2 = 36 mmHg; PO2 = 122 mmHg), a hypercapnic gas mixture (pH = 7.08; PCO2 75 mmHg; PO2 = 485 mmHg), or a hypoxic-hypercapnic gas mixture (pH = 7.09; PCO2 = 73 mmHg; PO2 = 124 mmHg). Control hearts were continuously perfused with Tyrode's solution aerated with carbogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108802 TI - The effect of four chemical forms of selenium on mammary tumor incidence in BALB/c female mice treated with 7-12-dimethylbenz[a]anthracene. AB - The study was conducted to determine the effect of four forms of selenium on inhibition of DMBA-induced mammary tumors. BALB/c virgin female mice were fed the AIN-76 diet containing 0.2 or 2.0 ppm Se as selenite, selenate, selenomethionine, or selenocystine prior to and for 6 months post DMBA-treatment. At necropsy, mammary glands were histologically treated for confirmation of adenocarcinomas and the livers were removed for analysis of glutathione-peroxidase (GSHPx) activity and selenium concentrations. Dietary levels or forms of selenium had no effect on body weights. Inorganic selenium fed at 2.0 ppm Se (selenite and selenate) decreased mammary tumor incidence, but organic selenium (selenomethionine and selenocystine) had no effect on mammary tumor incidence. Hepatic GSHPx activity was highest with the 2.0 ppm selenium as selenocystine diet, but hepatic selenium levels were highest with the 2.0 ppm selenium as selenite. This study showed that the dietary form of selenium affects inhibition of mammary tumorigenesis. Furthermore, the study suggested that the pathways for selenium incorporation into GSHPx and for tumor inhibition are different. PMID- 2108803 TI - Recombinant human interferon gamma exerts an anti-proliferative effect and modulates the expression of human leukocyte antigens A,B,C and DR in human urothelial cell lines. AB - In this study we have treated three malignant (TGrIII) and two pre-malignant (TGrII) urothelial cell lines with recombinant human interferon gamma (rHu-INF gamma). The malignant cells (HCV29-T112C1, Hu1703He and T24) were inhibited in growth by more than 50% after treatment with 100-1000 units of rHu-INF gamma/ml for 4 days as compared to untreated controls. The growth of the pre-malignant cell lines (HCV29 and Hu609) was not influenced to the same extent in the presence of rHu-INF gamma in the culture medium. Treatment with rHu-INF gamma increased the expression of monomorphic human leukocyte antigens (HLA) A,B,C as well as beta 2-microglobulin in all the cell lines tested, as demonstrated using a quantitative immunofluorescence assay. The tumourigenic cell lines increased their expression of HLA in a dose-dependent way, whereas treatment of the non tumourigenic cells with higher concentrations of rHu-INF gamma than 10 units/ml, did not increase the HLA-A,B,C expression further. None of the cell lines expressed HLA-DR unless treated with rHu-INF gamma. No correlation between tumourigenicity and the dose of rHu-INF gamma required for "de novo" induction of HLA-DR could be demonstrated. After removal of rHu-INF gamma from the medium, the expression of HLA-DR gradually decreased in less than 14 days, indicating that the expression of HLA-DR is not constitutive but dependent upon the presence of rHu-INF gamma. We conclude that human urothelial cells grown in vitro are sensitive to the anti-proliferative and major-histocompatibility-complex modulating effects of rHu-INF gamma, and that malignant urothelial cells are more sensitive than pre-malignant cells. Finally, our data indicate a possible role for rHu-INF gamma in the management of human bladder cancer. PMID- 2108804 TI - [A study on distribution characteristics of viral hepatitis and preventive strategy in Hangzhou]. AB - By using the method of predictive survey, 1248 cases of acute viral hepatitis, which have been definitely diagnosed, in urban district, water-net areas, semi mountainous and mountainous areas in Hangzhou were studied for the epidemiology and serum pathogenic typing in 1987. As a result, with the mixed infection of hepatitis A and hepatitis B at the rate of 1.20%, hepatitis A 69.71%, hepatitis B 7.13% non A non B hepatitis amounted to 21.96%. In urban and rural area, the percentage of hepatitis A ranked first while that non A non B hepatitis did second. The main risky factors in epidemicity of hepatitis A were: 1) the use of commode; 2) contact with the patients with hepatitis; 3) drinking unboiled water. Hepatitis A and hepatitis B transmitted mainly in the way of extra-intestines. Seeing dentist was the main risky factor. The relevant strategy was presented on the bases of the above-mentioned data. PMID- 2108805 TI - [Immune response and post inoculation reactions of simultaneous administration of hepatitis B vaccine with routine vaccine in children, III. Immune response and post inoculation reactions of simultaneous administration of hepatitis B vaccine and BCG, meningococcus group A polysaccharide vaccine]. AB - The results of the immune response and post inoculation reactions of simultaneous administration of BCG, meningococcus group A polysaccharide vaccine and hepatitis B vaccine were reported. 360 newborn babies (1-3 days of age) were divided into five groups. The babies in group No. 1 were vaccinated with hepatitis B vaccine alone, babies in group No. 2 were vaccinated with BCG for scarification within 3 days after delivery and meningococcus group A polysaccharide vaccine in 6 months of age; babies in group No. 3 were vaccinated with hepatitis B vaccine, BCG for scarification and Meningococcus group A polysaccharide vaccine simultaneously, babies in group No. 4 were vaccinated with intradermal BCG and Meningococcus group A polysaccharide vaccine separately, babies in group No. 5 were vaccinated with hepatitis B vaccine, intradermal BCG and meningococcus group A polysaccharide vaccine simultaneously. The results of the immune response of the combination of hepatitis B vaccine with BCG, meningococcus group A polysaccharide vaccine were similarly to the immune response observed after immunization of each vaccine alone in children. The general post inoculation reactions of all vaccines were mild. There was no significant difference among all 5 groups. The data showed that children could be immunized with hepatitis B vaccine, BCG and meningococcus group A polysaccharide vaccine simultaneously. PMID- 2108806 TI - Pseudomonas folliculitis: an outbreak associated with bromine-based disinfectants -British Columbia. PMID- 2108807 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters intrathymic T-cell development in mice. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered to 2-4-week-old mice (5, 25, and 50 micrograms/kg body wt.) and to in vitro cultures (10(-9) M) of fetal thymi. By monitoring thymocyte populations with respect to the differentiation antigens CD4 and CD8, it was found that the cell number in all thymocyte populations except for CD8+ decreased significantly compared with controls. In vivo the most marked decrease occurred among double negative (DN) and double positive (DP) cells, whereas in vitro, the DP cells were most severely affected. The cell number had already decreased to some extent by day 1 after a dose of 50 micrograms/kg body wt. of TCDD, although a severe reduction did not become apparent until day 4. There was a clear dose/response relationship between 5 and 50 micrograms/kg body wt. Autoradiography and liquid scintillation counting studies showed that incorporation of [3H]thymidine in the thymus had already decreased 24 h after TCDD treatment, with the decrease being even more pronounced at 48 h. By 96 h, the rate of cell proliferation had returned to approximately normal values. The results show that TCDD has a long-lasting effect on thymocyte abundance together with a transient effect on cell proliferation. This indicates that in addition to the initial effects of TCDD on cell proliferation, it may also more permanently disturb the normal process of elimination by means of selection. PMID- 2108808 TI - CCl4-induced increase of hepatocyte free arachidonate level: pathogenesis and contribution to cell death. AB - A significant increase of the intracellular level of free arachidonic acid was observed in intact rat hepatocytes after poisoning with very low concentrations of CCl4 (0.129-0.172 mM), shown not to exert direct solvent effect. It seems likely that activation of phospholipase A2 (PLA2) is the mechanism mainly responsible for the rise of cytosolic arachidonate, since the latter is prevented by the PLA2 inhibitors indomethacin and mepacrine. The CCl4-induced delay of arachidonic acid incorporation within the cell membrane phospholipids partly contributes to its intracellular accumulation in the early phases of the poisoning. The lack of any significant protection by metabolic inhibitors (SKF 525A, metyrapone), antioxidant compounds (promethazine, diphenylphenylenediamine DPPD) or antioxidant procedures (rat pretreatment with vitamin E) leads to exclude an involvement of CCl4 biotransformation in the increase of intracellular free arachidonate. Finally, the PLA2 inhibitors employed in this study did not afford protection against the enzymic leakage of CCl4-treated hepatocytes. PMID- 2108809 TI - Spermine stimulates the threonyl-tRNA formation in rat liver. AB - The effects of spermine have been studied on the aminoacylation reaction catalyzed by rat liver threonyl-tRNA synthetase. Spermine can not replace Mg2+ in this reaction. However, a stimulatory and synergistic effect was observed on the threonyl-tRNA formation, in the presence of spermine and suboptimal concentration of Mg2+. Other divalent cations like Ba2+, Ca2+, Mn2+ and Co2+ can substitute Mg2+ in the threonyl-tRNA formation, but in all these cases spermine had no significant effect. Spermine prevented the inhibitory effects caused by excess of ATP or tRNA on the aminoacylation reaction. Association constants were determined by equilibrium dialysis for the tRNA-spermine complex (Ka = 3.7 x 10(3) M-1) and by differential spectrophotometry for the ATP-spermine complex (Ka = 7.8 x 10(3) M-1). No enzyme-spermine complex could be detected by equilibrium dialysis. Some roles have been ascribed for the polyamine spermine in the stimulation of the threonyl-tRNA formation. ATP-spermine and tRNA-spermine can not function as substrates for the threonyl-tRNA synthetase, since Mg2+ is indispensable. The stimulatory effect by spermine is important considering the physiological concentration of Mg2+ in the tissues. Probably in vivo spermine would have a relevant role lowering the real Mg2+ concentration required in the aminoacylation reaction. PMID- 2108810 TI - Conjugation of benzo[a]pyrene metabolites by freshwater green alga Selenastrum capricornutum. AB - Benzo[a]pyrene (BaP) undergoes metabolic transformation in mammals via oxidative, hydrolytic, and conjugative processes; however, little is known concerning BaP conjugation in freshwater algae. It has been shown in this laboratory that BaP is metabolized by Selenastrum capricornutum via a dioxygenase pathway. This study describes the conjugation of BaP metabolites by a green alga, Selenastrum capricornutum. Cultures were exposed to 1160 micrograms/l [14C]BaP for 4 days at 23 degrees C under gold fluorescent lights on a diurnal cycle of 16 h light, 8 h dark. Of the total metabolites in the algal culture, 89% were present in media. BaP and non-conjugated metabolites were separated from conjugated metabolites by chromatography on neutral alumina columns using solvents of increasing polarity. Seventy-one percent of the BaP metabolites were conjugates of which 12.2%, 12.0% and 12.4% were sulfate ester and alpha- and beta-glucose conjugates, respectively. Conjugates that coeluted with sulfate esters were hydrolyzed with arylsulfatase, alpha- or beta-glucosidase; high performance liquid chromatography (HPLC) analysis indicated that the major product of each enzymatic hydrolysis was the 4,5-dihydrodiol (87.2, 69 and 53%, respectively). Eighty-six percent of the conjugates were acid labile following incubation for 2 h in 4 N HCl at 37 degrees C. To our knowledge this is the first demonstration of the metabolism of a polynuclear aromatic hydrocarbon by a freshwater green alga through a dioxygenase pathway and subsequent conjugation and excretion. PMID- 2108811 TI - Halothane inhibits hypoxic pulmonary vasoconstriction in the presence of cyclooxygenase blockade. AB - Using an isolated lung the effects of halothane on hypoxic pulmonary vasoconstriction (HPV) were studied in the presence of cyclooxygenase blockade. The pulmonary vasculature can be divided into arterial, middle and venous segment resistances. Analysis of the vascular pressure-flow relationship further separates resistance into a flow dependent resistance (1/slope) and a zero-flow pressure intercept (PCRIT). We ventilated six lobes with control (35 per cent O2) and hypoxic (three per cent O2) gas mixtures with the addition of either 0, 0.5, 1.0, or 2.0 per cent halothane. We found that after addition of indomethacin (5 mg.kg-1), ventilation with three per cent O2 increased total resistance by 87 per cent over baseline with the increase primarily in the middle vascular segment. During normoxic ventilation PCRIT was 7.9 cm H2O and this increased significantly with hypoxia to 11.5 cm H2O). Only 2.0 per cent halothane blocked the increases in middle segment resistance and in PCRIT. We conclude that following cyclooxygenase blockade, halothane inhibits HPV by acting on middle segment vessels. PMID- 2108812 TI - Autoregulation and the CO2 responsiveness of cerebral blood flow after cardiopulmonary bypass. AB - Cerebral blood flow (CBF) was measured by 133Xe clearance to determine whether there were any residual effects of cardiopulmonary bypass (CPB) on the CBF response to changes in arterial PCO2 or blood pressure in the early (3-8 hr) post CPB period. During CPB, the nine patients studied were managed according to alpha stat, temperature uncorrected, pH management. The mean +/- SD increase in CBF resulting from an increase in PaCO2 (1.35 +/- 0.5 ml.100 g-1.min-1.mmHg-1 PaCO2) was within the normal range, indicating appropriate CBF response to a change in PaCO2. There were no significant differences in CBF, being 25.7 ml.100 g-1.min-1 at a mean arterial blood pressure of 70 mmHg and 26.5 ml.100 g-1.min-1 at 110 mmHg, demonstrating intact cerebral autoregulation over this pressure range. We conclude that cerebral autoregulation and CO2 responsiveness are preserved in the immediate postoperative period after CPB using alpha-stat pH management. PMID- 2108813 TI - Accuracy of end-tidal PCO2 measurements using a sidestream capnometer in infants and children ventilated with the Sechrist infant ventilator. AB - To determine the accuracy of end-tidal PCO2 (PETCO2) measurements analyzed with a sidestream capnometer in infants and children whose lungs were ventilated with a Sechrist infant ventilator and an Ayre's t-piece, we compared PETCO2 measurements obtained from the proximal (PETCO2-p) and distal (PETCO2-d) ends of the tracheal tube to arterial PCO2 (PaCO2) in 37 healthy infants and children between 1.3 and 24.5 kg. Both PETCO2-p and PETCO2-d accurately approximated PaCO2, however, the mean (+/- SD) arterial to end-tidal PCO2 difference (delta(a-ET)PCO2) was significantly greater with proximal (1.27 +/- 1.54 mmHg) than with distal sampling (0.64 +/- 1.64 mmHg) (P less than 0.01). In the subgroup of patients who weighted less than 12 kg, the delta(a-ET)PCO2 using proximal gas sampling (1.94 +/- 1.29 mmHg) was also significantly greater than it was using distal sampling (0.74 +/- 1.31 mmHg) (P less than 0.001). We conclude that although statistically different, both proximal and distal estimates of PETCO2 provide acceptable estimates of PaCO2 in healthy infants and children who are ventilated with a Sechrist infant ventilator and an Ayre's t-piece system. PMID- 2108814 TI - End-tidal carbon dioxide measurements in critically ill neonates: a comparison of side-stream and mainstream capnometers. AB - To determine whether end-tidal PCO2 (PETCO2) measurements obtained with two infrared capnometers accurately approximates the arterial PCO2 (PaCO2) in critically ill neonates, simultaneous measurements of PETCO2 were obtained from the distal and proximal ends of the tracheal tube with a sidestream capnometer (Puritan Bennett/Datex--BP/D) and from the proximal end with a mainstream capnometer (Hewlett-Packard-HP) in 20 intubated neonates. Distal sidestream PETCO2 and mainstream PETCO2 correlated with the PaCO2 (r2 = 0.66 and 0.61, respectively) within the range of 26-57 mmHg PaCO2. However, proximal PETCO2 with the sidestream capnometer correlated very poorly (r2 = 0.09) with PaCO2. The slope of the least square regression line for the distal sidestream capnometer, 0.67, was significantly less than that for the mainstream capnometer, 0.78 but both were significantly greater than that for the proximal sidestream capnometer, 0.39 (P less than 0.05). The slope of the regression for the proximal sidestream capnometer did not differ significantly from horizontal. Insertion of the mainstream sensor for the HP capnometer significantly increased the transcutaneous CO2 when compared with preinsertion values. We conclude that both distal sidestream and mainstream capnometry provide accurate estimates of the PaCO2 in critically ill neonates. PMID- 2108815 TI - Anticonvulsant therapy increases fentanyl requirements during anaesthesia for craniotomy. AB - This study was designed to determine whether patients receiving chronic anticonvulsant therapy demonstrate an altered requirement for fentanyl during anaesthesia. Sixty-one patients undergoing craniotomy were studied; 20 controls (MED = 0) who had never received anticonvulsants and 41 epileptics in whom therapeutic plasma concentrations of either one (MED = 1), two (MED = 2), or three (MED = 3) different anticonvulsants were documented. During anaesthesia with 60-70 per cent N2O in O2 and 0.2 per cent isoflurane, a maintenance dose (MD) of fentanyl was administered using a continuous variable-rate IV fentanyl infusion, supplemented by intermittent 50 micrograms IV boluses. In order to define the minimal dosage of fentanyl required, the MD was titrated according to increases or decreases in the heart rate and/or mean arterial pressure exceeding 15 per cent of baseline ward values. A progressively higher fentanyl MD was required in the epileptic patients (MED = 1-4.3 +/- 0.5 microgram.kg-1.hr-1; MED = 2-5.4 +/- 0.6; MED = 3-7.6 +/- 0.6) compared with the control MD (MED = 0-2.6 +/- 0.5) (P less than 0.001). These findings indicate that there appears to be a dose-effect relationship between the number of anticonvulsants received and the maintenance dose of fentanyl required during balanced anaesthesia. PMID- 2108816 TI - The benefit of cisplatin-based polychemotherapy for adenocarcinoma of the lung. The Kyushu Lung Cancer Chemotherapy Study Group. AB - We studied the efficacy of cisplatin-based polychemotherapy for adenocarcinoma of the lung. A total of 136 patients were randomized for treatment with either cyclophosphamide, Adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT). Radiation was given to the chests of patients at stage III. The differences in the response rate (35% in the CAPM arm and 13% in the MCT arm) were statistically significant (P less than 0.01). However, the significant difference was observed in stage-IV patients (CAPM, 33%; MCT, 4%; P less than 0.001) and not in stage-III patients (CAPM, 40%; MCT, 40%). The median period of survival was 9.5 months for the CAPM arm and 5.5 months for the MCT arm (P less than 0.035, Wilcoxon-Gehan test; P less than 0.1, log-rank test). Improved median survival for the CAPM regimen was demonstrated only by stage-IV patients (CAPM, 10 months; MCT, 5.5 months; P less than 0.025, Wilcoxon Gehan test; P less than 0.05, log-rank test). The duration of the response, including PRs and NCs, was significantly different depending on the treatment, showing 5 months for the CAPM arm and 3 months for the MCT arm (P less than 0.05). The significant difference was also only observed in stage-IV patients. Myelosuppression was more severe with CAPM than with the MCT regimen. Nausea and vomiting were significantly increased in patients receiving the CAPM regimen. However, all toxicities were acceptable and there were no treatment-related deaths. We concluded that cisplatin-based chemotherapy, CAPM therapy, was of more benefit to patients with adenocarcinoma of the lung than MCT therapy. PMID- 2108817 TI - Properties of aflatoxin-DNA adducts formed by photoactivation and characterization of the major photoadduct as aflatoxin-N7-guanine. AB - Aflatoxin-DNA adducts were formed by microsomal and photoactivation, using nick translated DNA labelled with 14C in each of the DNA bases [3H]AFB1 and [3H]AFB2. DNA adducts were analysed by HPLC of DNA hydrolysates, and were characterized as double labelled peaks with specific retention times. The only AF-DNA adducts which were detected in significant amounts were guanine adducts, irrespective of the type of aflatoxin used or the mode of its activation. No stable adduct with adenine, cytosine or thymine was detected. UV spectra, proton NMR spectroscopy and mass spectrometry are consistent with the notion that the major AFB1-DNA photoadduct is the N7-guanine adduct. This report provides direct evidence for the existence of aflatoxin photoadducts formed on DNA. PMID- 2108819 TI - Metabolism and activation of the pancreatic carcinogen N-nitrosobis(2 oxopropyl)amine by isolated hepatocytes and pancreatic cells of the Syrian hamster. AB - The metabolism of the pancreatic carcinogen N-nitroso-bis(2-oxopropyl)amine (BOP) was studied using primary hepatocytes and acinar and duct cells isolated from Syrian hamsters. Metabolic activation of BOP was verified by detecting its conversion to CO2 covalently bound metabolites and soluble products containing the alpha-carbon of the nitrosamine. At concentrations below 0.2 mM, BOP was completely activated by hepatocytes within 60 min. At high substrate concentration (1 mM) or high cell density (5 x 10(6) cells/ml), reduction of BOP to N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine and N-nitrosobis(2 hydroxypropyl)amine contributed significantly to the metabolic profile. The conditions which favored metabolic activation of BOP were used to compare metabolism by hepatocytes and pancreatic cells. Under such conditions, the ratio of activation products formed by hepatocytes versus those formed by acinar cells was 14.5:1; the corresponding ratio for covalently bound metabolites was 19:1. Hepatocytes activated BOP 106 times more rapidly than duct cells as determined from yields of activation products or 152 times more rapidly as determined from labeling of cellular macromolecules. Acinar cells showed a higher capacity for metabolic activation than duct cells. The ratio for the yield of activation products from acinar versus duct cells was 4.3:1; the corresponding ratio for covalent binding was 5.8:1. The relatively low capacity of pancreatic cells for activation of BOP compared to hepatocytes is in agreement with the low levels of DNA binding in the pancreas compared to other organs after administration of BOP to the hamster in vivo. The observation that the ratio for total covalent binding of BOP in hepatocytes versus acinar cells was higher than that seen previously for the liver versus the pancreas in vivo is consistent with the hypothesis that alkylating agents derived from BOP reach the pancreas after formation in other organs. The liver would be the prime source for such alkylating agents. PMID- 2108818 TI - Involvement of singlet oxygen in photoactivation of aflatoxins B1 and B2 to DNA binding forms in vitro. AB - UVA-activated aflatoxin B1 (AFB1) and AFB2 bound covalently to DNA. The rate of binding increased in D2O versus H2O and decreased by diazabicyclo-octane, azide, aniline, 2-naphthylamine and by efficient stripping of oxygen. Similarly to DNA binding, singlet oxygen (1O2) formation increased in D2O and was inhibited by singlet scavengers, as judged by the formation of malonaldehyde from linolenic acid. The above argue for the involvement of 1O2 in aflatoxin photoactivation to DNA-binding species. A model for the mechanism is proposed. PMID- 2108820 TI - Menarche, menses, and menopause: a brief review. AB - Reproductive maturation, the menstrual cycle, and the transition to postreproductive life are complex processes. Detailed understanding of reproduction underlies logical patient management. Greater understanding of physiology has brought about better control of ovulatory problems and the beginnings of a logical approach to other problems such as androgen excess, where two complex systems overlap. PMID- 2108821 TI - Initiation and growth of ectopic neurites and meganeurites during postnatal cortical development in ganglioside storage disease. AB - The incidence of cortical pyramidal neurons displaying meganeurites or enlarged axon hillocks with ectopic spines and neurites was evaluated developmentally using feline models of GM1 and GM2 gangliosidosis. Results of these studies demonstrated that the onset of ectopic neurite growth occurred after the elaboration of dendrites on cortical pyramidal neurons, and that the time of onset of this renewed dendritogenesis was similar in the two diseases. Initiation and growth of ectopic neurites also correlated in a general way with onset and progression of clinical deterioration in both diseases. In GM1 gangliosidosis there was a greater tendency toward formation of meganeurites, whereas in cats with GM2 gangliosidosis the growth of ectopic axon hillock neurites without meganeurites predominated. At end-stage disease in GM2 gangliosidosis, nearly 90% of pyramidal cells displayed some degree of axon hillock neurite growth as opposed to less than half this number for GM1 gangliosidosis cats at the same age. These data are consistent with the hypothesis that there are two separate driving forces behind these somadendritic abnormalities of pyramidal neurons in the gangliosidoses. Excessive intraneuronal accumulation of storage vacuoles accounts for the formation of meganeurites, whereas some type of intrinsic metabolic defect results in axon hillock neurite growth which in turn offers new surface area for synaptic input. Currently available data indicate that GM2 or GM3 ganglioside, or a closely related metabolic product other than GM1 ganglioside, may be primarily associated with the growth of ectopic dendritic processes on morphologically mature neurons in storage diseases. PMID- 2108822 TI - Measuring free thyroxin by using magnetic antibody-containing microcapsules. AB - We describe a novel magnetic-separation microencapsulated antibody displacement assay for free thyroxin. The method is rapid (results available in just over an hour), with a detection limit of 3 pmol/L, and an interassay precision of less than 10% over the range 8-75 pmol/L. Results are not influenced by changes in the concentration of thyroxin-binding globulin or albumin, nor by the presence of circulating anti-thyroxin antibodies or physiological concentrations of nonesterified (free) fatty acids. A reference interval of 8.4-18.4 pmol/L was established for a large euthyroid adult population. Patients with various nonthyroidal illnesses exhibited a similar reference interval (6.2-17.4 pmol/L). Results from pregnant women, at all stages of gestation, were within the nonpregnant euthyroid reference interval. Complete discrimination was obtained between the euthyroid reference interval and values from patients with untreated thyrotoxicosis (24-75 pmol/L). Excellent, though incomplete, discrimination was obtained for patients with untreated hypothyroidism (less than 3.0-9.0 pmol/L). Results for a group of patients defined as having compensated euthyroidism (5.0 15 pmol/L) showed considerable overlap with the euthyroid reference interval. Patients taking thyroxin, who were clinically euthyroid and whose serum concentration of thyrotropin was within its euthyroid reference interval, had free thyroxin concentrations in the range 13.4-24.2 pmol/L. We discuss the validity of this assay in clinical practice. PMID- 2108823 TI - Thyrotoxic atrial fibrillation: an underdiagnosed or overdiagnosed condition? AB - Hyperthyroidism has been considered to be underdiagnosed as a pathogenetic factor for atrial fibrillation, according to results of thyroliberin stimulation tests. We assessed, clinically and biochemically, thyroid function in 110 ambulatory patients with atrial fibrillation [mean age 64 (SD 11) years] from a group of consecutive cases referred to a specialist cardiology unit during one year. Patients finally categorized as euthyroid (n = 100) commonly presented with one or more symptoms or signs considered to be typical for thyrotoxic patients. Three patients (2.7%; 95% confidence interval, 0-7.5%) fulfilled criteria for hyperthyroidism, but only one was identified from clinical examination. The thyroliberin stimulation test (performed in all patients) identified another seven patients who might have been classified as hyperthyroid according to commonly used criteria for an abnormal thyrotropin response. However, none of these seven patients was judged as hyperthyroid after follow-up. Their thyrotropin concentrations were all above the detection limit for the immunoenzymometric assay. With few exceptions, they had thyroid hormone concentrations within reference limits calculated from the results for the 100 euthyroid subjects, and their concentration ratio for free 3,5,3' triiodothyronine to free thyroxin, 0.31 (SD 0.05), was lower than that found in the euthyroid group [0.38 (SD 0.08), P less than 0.05]. We conclude that (a) criteria for evaluating results of the thyroliberin stimulation test should be revised, (b) this test is still useful in evaluating suspected cases of hyperthyroidism, for which results of current, improved methods for thyrotropin determination are equivocal, and (c) improved diagnostic methods should be used to characterize the relative importance of hyperthyroidism as a causal factor for atrial fibrillation. PMID- 2108824 TI - Serum carbonic anhydrase III and myoglobin concentrations in acute myocardial infarction. AB - Serum concentrations of myoglobin (S-Myo) and carbonic anhydrase III (S-CA III; EC 4.2.1.1), a skeletal muscle-specific protein, were measured by RIA in 26 patients with acute myocardial infarction, 14 patients with neuromuscular diseases, and six healthy subjects before and after physical exercise. S-Myo was increased in infarct patients, whereas S-CA III was not altered. In patients with neuromuscular diseases and in healthy subjects after physical exercise, both S Myo and S-CA III were significantly increased. S-CA III and S-Myo also showed identical peak times, 2 h postexercise. The S-Myo/S-CA III ratio was always higher in infarct patients than in the other groups. Thus, the combination of S CA III and S-Myo determinations is useful to differentiate whether serum myoglobin is originating from myocardium or from skeletal muscle. PMID- 2108825 TI - Polyclonal antibody-based enzyme-linked immunosorbent assay of alpha 1-acid glycoprotein. AB - This is a noncompetitive enzyme-linked immunosorbent assay for measuring low concentrations (2 to 100 micrograms/L) of human alpha 1-acid glycoprotein (AGP; orosomucoid). The method is based on a simple "sandwich" technique involving polyclonal rabbit antisera against AGP. Mean within-run and total (between-run) CVs were 6.2% and 9.7%, respectively. Analytical recovery, tested in various biological fluids, averaged 101%. The technique has been successfully applied to diluted biological fluids such as bronchoalveolar lavage, cerebrospinal and amniotic fluids, and hepatocyte-culture supernates. Because of its analytical validity and the commercial availability of the reagents, this assay is suitable for large-scale determinations of AGP concentrations in those biological fluids in which its concentration is relatively low. PMID- 2108826 TI - Biological factors affecting concentrations of serum LpAI lipoprotein particles in serum, and determination of reference limits. AB - We used an electroimmunoassay to measure LpAI lipoprotein particles (lipoproteins containing apolipoprotein AI but not apolipoprotein AII) in serum of a presumably healthy population of about 1000 subjects, noting sex- and age-related variations for the age interval four to 70 years. Results were higher for women than men. For males, the value for the 50th percentile of the distribution was highest in the 10- to 14-year subgroup, 0.69 g/L, decreasing to 0.60 g/L in adults. For females, the values increased regularly, from 0.59 g/L at ages four to 10 years to 0.79 g/L after age 55 years. The influence of puberty, menopause, oral contraceptives, alcohol consumption, and morphometric characteristics was studied. Only being overweight by more than 20% statistically influenced LpAI values in men and in women. We used these results to select a reference population and to establish reference limits of LpAI at ages 25 to 35 years: 0.40 0.95 g/L for men and 0.46-1.05 g/L for women. PMID- 2108827 TI - Carbonic anhydrase III as a serum marker for diagnosis of rhabdomyolysis. PMID- 2108828 TI - Rapid, automated enzyme immunoassay for follitropin with the Abbott IMx analyzer. PMID- 2108829 TI - Determination of albumin-bound thyroxin in serum. PMID- 2108830 TI - Fundamental problem with assays of apolipoprotein A-I. PMID- 2108831 TI - Apolipoprotein A-I concentrations in serum: a pragmatic approach to assessing risk of heart disease. PMID- 2108832 TI - Kawasaki disease and oxidative metabolism. AB - The plasmid lipid peroxidation products: malonyldialdehyde (MDA), organic hydroperoxides (OHP) and zinc peripheral values were analysed in seven children with Kawasaki disease, in the acute phase, before and after treatment with intravenous immunoglobulins. In the acute phase, plasma levels of MDA (2.95 +/- 0.30 mumol/l, control group: 2.52 +/- 0.08 mumol/l) and OHP (235 +/- 65 mumol/l, control group: 120 +/- 10) were increased (p less than 0.05 and p less than 0.01). Moreover, plasma zinc levels were significantly decreased (10 +/- 2.15 mumol/l versus 15.6 +/- 2.5 mumol/l in control group, p less than 0.05). After treatment with immunoglobulins, MDA, OHP and plasma zinc levels returned to normal. The parallel normalisation of clinical injury draws attention to the possible role of oxygen intermediates in connective tissue degradation and in the pathogenesis of vascular abnormalities in Kawasaki disease. PMID- 2108833 TI - Early antibody responses in human schistosomiasis. AB - Early diagnosis is important when handling patients with acute schistosomiasis. This state is usually more severe in travellers and tourists than in the immune, resident patients. With increased travelling to areas endemic for schistosomiasis, a tool is needed to solve the problem of differential diagnosis due to the non-specific symptoms of the early stages of the disease. Early appearance of antibodies against excretory/secretory antigens of the intestinal tract in the adult worm was seen in six individuals recently infected with Schistosoma mansoni, using an indirect immunofluorescence technique. The antibodies were of IgM, IgG and IgA classes, and of the IgG1, IgG3 and IgA1 subclasses as detected by ELISA using an antigen preparation of adult worm. On immunoblots, using a freeze-dried adult worm antigen, IgG1 and IgG3 antibodies recognized antigens of 32-35 kD. Antibodies against these antigens could thus be a marker of early infection in previously non exposed visitors to endemic areas. PMID- 2108834 TI - Peripheral B-lymphocyte markers and function in IgA nephropathy. AB - Peripheral blood B-lymphocyte markers and functions were observed in 21 patients with IgA nephropathy (IgA NP) and in 16 controls. IgA NP B lymphocytes expressed significantly higher positivity with Leu 1 (CD 5) monoclonal antibody than controls. CD 5 positive B lymphocytes are thought to be a distinct subset of the B cells (autoregulatory B lymphocytes) inducible in IgA NP by lipopolysaccharide (LPS) stimulation parallel to the higher expression of surface IgM heavy chain positivity. The activated state of IgA NP B lymphocytes has been proved by their higher OKIa (HLA-DR) positivities but lower IOB1a (CD 21, C3d-receptor) and decreased IgG-Fc-receptor (ox-rosette) expression. IgA NP B lymphocytes showed a higher IgA but also IgG and IgM polyclonal immunoglobulin production than control B lymphocytes in co-cultures with T lymphocytes. Not only regulatory T lymphocyte subsets but also serum derived from IgA NP patients stimulated the immunoglobulin production of IgA NP B cells. PMID- 2108835 TI - Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery. AB - To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias. PMID- 2108836 TI - Neurofibroma in a patient with von Recklinghausen's disease seen as a malignant schwannoma. A case report. AB - A rapidly growing, malignant schwannoma occurred in a 46-year-old woman with neurofibromatosis. Computed tomography, isotope bone scan, chest roentgenogram, and angiogram are helpful in determining the local extent and distant spread of such musculoskeletal tumors and are useful in planning appropriate surgical management. A well-planned biopsy, however, is essential to accurately determine the histologic diagnosis of the tumor. Clinical and roentgenographic presentation of some benign lesions may mimic malignant tumors. To confirm the diagnosis of a malignant or benign tumor, it is advisable to examine the musculoskeletal tumor histologically before proceeding with the definitive treatment, even if the clinical presentation strongly suggests malignancy. PMID- 2108837 TI - Pilot study to determine the interaction of oxiracetam with antiepileptic drugs. AB - Oxiracetam, a nootropic drug, could be of potential use in the treatment of memory disturbances in patients with epilepsy who are using antiepileptic drugs. The half-life of oxiracetam appears to be influenced by the concomitant use of carbamazepine or valproic acid, necessitating more frequent administration of oxiracetam than is recommended for other conditions. No effect was observed on the serum concentrations of these antiepileptic drugs by oxiracetam. Long term concurrent use of oxiracetam and antiepileptic agents does not appear to be contraindicated. PMID- 2108839 TI - Are three views necessary to examine acute ankle injuries? PMID- 2108840 TI - Rising health care costs: telling the truth! PMID- 2108838 TI - Effect of early and delayed difluoromethylornithine pretreatment upon cyclophosphamide chemotherapy. AB - The Dunning R3327 MAT-LyLu prostatic adenocarcinoma was utilized to study the effectiveness of an early versus delayed difluoromethylornithine (DFMO)-induced polyamine-depleted environment on cyclophosphamide (CTX) chemotherapy. DFMO (2%) was administered either at the time of tumor inoculation (early) or 36 h after tumor implantation (delayed). CTX (50 mg/kg) was administered to both DFMO groups in two doses; the first 36 h after initiation of DFMO therapy, and the second 1 week later. Each protocol (early and delayed) for combined DFMO/CTX chemotherapy significantly reduced tumor sizes with the earlier DFMO protocol appearing slightly more effective (p less than 0.001 and 0.02, respectively). DFMO administered alone was not significantly effective with either protocol. PMID- 2108841 TI - Chromosome mapping of the human RAS-related RAP1A, RAP1B, and RAP2 genes to chromosomes 1p12----p13, 12q14, and 13q34, respectively. AB - Three human cDNAs encoding new RAS-related cDNAs, designated RAP1A, RAP1B, and RAP2, have been isolated previously. The encoded proteins are highly related to RAS in the effector region and share an overall identity with RAS of approximately 50%. Using the complete cDNAs or parts thereof as probes, each RAP gene has been localized on human chromosomes by in situ hybridization. The three genes RAP1A, RAP1B, and RAP2 have been assigned to chromosome bands 1p12----p13, 12q14, and 13q34, respectively. PMID- 2108842 TI - The thyroglobulin gene is syntenic with the MYC and MOS protooncogenes and carbonic anhydrase II and maps to chromosome 14 in cattle. AB - Using a panel of bovine x Chinese hamster hybrid somatic cells, sequences homologous to genes spanning human chromosome arm 8q have been syntenically assigned in cattle. Thyroglobulin (TG), carbonic anhydrase II (CA2), and the protooncogenes MYC and MOS were assigned to a newly identified bovine syntenic group, U23. Additionally, in situ hybridization of the thyroglobulin probe to bovine metaphase chromosomes revealed this syntenic group to be on bovine chromosome 14 and the bovine thyroglobulin gene to reside at 14q12----q15. PMID- 2108843 TI - Improvement in exercise performance after pulmonary arteriovenous malformation embolization. AB - Balloon or coil embolization has become established therapy for multiple PAVMs. We were able to evaluate a 32-year-old woman with multiple PAVMs characterized by significant orthodeoxia, intrapulmonary shunt, dyspnea and limited exercise tolerance before and after balloon and coil embolization. After embolization of three of her largest PAVMs, repeat evaluation revealed improvement in her symptoms, orthodeoxia and intrapulmonary shunt. She was able to exercise two additional work rates with a sustained improvement in oxygenation, a decrease in the P(A-a)O2 difference and higher maximum oxygen consumption. These studies provide objective evidence of persistent improvement in function and endurance at rest and during exercise after embolization. PMID- 2108844 TI - Attenuation of the metabisulfite-induced bronchoconstrictive response by pretreatment with cromolyn. AB - In a retrospective analysis of 1,544 patients who underwent provocative challenge with metabisulfite at the National Jewish Center between 1983 and 1987, an abnormal airway response to metabisulfite was found in 52 patients, an incidence of 3.4 percent. There was no relationship between this abnormal airway responsiveness to metabisulfite and the degree of airway obstruction present, or the degree of airway reactivity as assessed by the response to inhaled bronchodilator or exercise testing. In a pilot study, we found that the administration of cromolyn sodium prior to metabisulfite challenge markedly attenuated the abnormal bronchoconstrictive response in nine of ten patients. We conclude that a metabisulfite-induced bronchoconstrictive response cannot be predicted on the basis of the degree of airway obstruction or airway reactivity and that pretreatment with cromolyn sodium may attenuate the abnormal response. PMID- 2108845 TI - Hypophosphatemia in course of chronic obstructive pulmonary disease. Prevalence, mechanisms, and relationships with skeletal muscle phosphorus content. AB - Serum phosphorus levels (Ps), dietary intake of phosphorus, and renal phosphate handling indexes were evaluated in 158 patients with chronic obstructive pulmonary disease (COPD) of varying degrees of severity; moreover, skeletal muscle phosphorus content (Pm) was measured in muscle samples obtained by quadriceps femoris needle biopsy in 14 of the same patients. Hypophosphatemia (Ps less than or equal to 2.5 mg/dl) was found in 34 (21.5 percent) of 158 patients without differences between groups of COPD patients presenting increasing severity of respiratory illness. No relationship was found between serum levels and dietary intake of phosphorus; hypophosphatemia was associated with low renal phosphate threshold (TmPO4/GFR) values in 31 (91 percent) of 34 patients. The prevalence of hypophosphatemia was significantly higher among COPD patients taking one or more drugs commonly used in COPD and known as negatively influencing renal phosphate handling: xanthine derivatives, corticosteroids, loop diuretics, and beta 2-adrenergic bronchodilators. Short-term administration of therapeutic doses of these drugs in COPD patients previously not taking any drug reduced TmPO4/GFR values; phosphaturic effect of short-term theophylline administration on renal phosphate handling was additive to that of long-term assumption of the drug. Muscle phosphorus content was both reduced in COPD patients as compared with control subjects and significantly correlated to serum phosphorus levels and to TmPO4/GFR values. The present investigation revealed a high prevalence of hypophosphatemia among COPD patients as well as a defect in renal phosphate reabsorption secondary, at least in part, to pharmacologic therapy. Moreover, it also suggests that in COPD patients muscle phosphorus content is likely to be reduced in presence of hypophosphatemia. PMID- 2108846 TI - Polysomnography early after uvulopalatopharyngoplasty as a predictor of late postoperative results. AB - We performed nocturnal diagnostic polysomnography (PSG 1), PSG early after UPPP on the second to the fifth postoperative night (PSG 2) and PSG late after UPPP (PSG 3) six or more weeks after surgery, on 15 male patients with obstructive sleep-disordered breathing. On PSG 1, the A + H/I for the group was 66.6 +/- 8.8 (mean +/- SE). During non-REM sleep the A + H/I on PSG 3 (29 +/- 10) was lower than it was on PSG 2 (54.3 +/- 11.3) (p = 0.004) and lower than that on PSG 1 (70.8 +/- 10.3) (p = 0.003). Similarly, during non-REM sleep, the AI on PSG 3 (16.1 +/- 7.4) was less than that on PSG 2 (39.1 +/- 10.4) (p = 0.003) and less than that on PSG 1 (41.7 +/- 9.6) (p = 0.015). In the eight patients in whom REM sleep was recorded on all three PSGs, there was no difference with respect to A + H/I or AI. The nadir of SaO2 during non-REM sleep was higher during PSG 3 than during PSG 1 (p = 0.002), but not different from that on PSG 2. There were no differences among the three studies with respect to REM-related nadirs of SaO2; however, there was a good deal of interindividual variability across the three PSGs. In general, individuals with satisfactory amelioration of sleep-disordered breathing on PSG 2 demonstrated similar improvement on PSG 3. Patients who did not have a substantial improvement in the early postoperative period often had improvement on PSG 3, but there was a good deal of interindividual variability in this regard. We conclude that PSG within a few days following UPPP is warranted in patients with obstructive sleep-disordered breathing to determine if there has been worsening of upper airway function or oxygenation (or both) during sleep in the early postoperative period. A satisfactory result early after UPPP suggests that a late postoperative PSG is unnecessary, with savings in cost and the convenience. PMID- 2108847 TI - The effects of heterologous platelet transfusion on pulmonary function during ARDS. AB - Pulmonary platelet sequestration has been implicated in the pathophysiology of ARDS. Since HPTs are frequently given therapeutically to patients with ARDS, a serious concern clinically has been the possibility that platelet transfusions might worsen pulmonary function in such patients. To prospectively evaluate this issue, we assessed the effects of HPT on two parameters of pulmonary function: (1) Qs/Qt; and (2) PVR. Measurements were made immediately before and at 1 hour and 4 hours after HPT in 16 patients during 18 separate episodes of ARDS and in 11 control patients. The ARDS had been present for at least 48 hours in all patients at the time of study. Prior to HPT, patients with ARDS had significantly worse pulmonary function compared to control subjects. Although a small number of patients with ARDS had large changes in PVR and Qs/Qt after HPT, no group showed significant changes in any pulmonary parameter following transfusion. Neither individual changes in the platelet count after HPT nor the duration of ARDS before HPT was associated with changes in pulmonary function after platelet administration. We concluded that therapeutically required HPT did not significantly worsen pulmonary function at up to four hours after transfusion in this group of patients with well-defined and fully evolved (greater than 48-hour duration) ARDS. The reason for this absence of effect was not known, but the pathogenesis of ARDS might only be susceptible to alteration during the early developmental stage. PMID- 2108848 TI - Fiberoptic bronchoscopy in ventilated patients. Evaluation of cardiopulmonary risk under midazolam sedation. AB - One hundred seven acutely ill ventilated patients were prospectively studied to ascertain the severity and frequency of alterations in gas exchange and hemodynamic parameters during brief bronchoscopy. Sedation was performed using midazolam (0.1 mg/kg IV) without topical anesthesia. An average decline in PaO2 of 26 percent was observed at the end of the procedure, compared to the baseline value, and this was associated with a mild increase in PaCO2 in spite of the use of a special adapter. Alterations in mean systolic blood pressure appeared to be modest, consisting of a 10 percent decrease from the control level, related to sedation, and a 10 percent rise from baseline during the procedure, associated with a concomitant mild tachycardia. At that time, central hemodynamic measurements performed in a subset of 31 patients showed a significant increase in cardiac output associated with higher pulmonary wedge pressure. Fourteen patients developed hypoxemia of less than 60 mm Hg on FIO2 adjusted to 0.8. Of the ten risk factors univariately associated with hypoxemia, only the presence of ARDS (p less than 0.001) and "fighting" the ventilator during the procedure (p less than 0.05) remained significant after stepwise logistic regression. Attempts to prevent hypoxemia in critically ill patients should focus on inducing complete sedation, with careful attention to hemodynamic status, or providing maximal levels of oxygen to the ventilator (or both). PMID- 2108849 TI - Effects of intravenous fat emulsion on respiratory failure. AB - The effects of intravenous fat emulsion on ventilated normal, diseased or distressed lungs were studied. Forty-eight patients with different types of respiratory failure were divided into four groups. Group A was composed of the patients with a normal lung condition; group B, patients with infectious pulmonary condition and respiratory failure; group C, patients with COPD and respiratory failure; and, group D was composed of the patients with ARDS due to various causes. Five hundred milliliters of 10 percent fat emulsion was infused within 4 h as partial parenteral nutritional support. We concluded that intravenous fat infusion decreased PaO2/FIO2 and increased P(A-a)O2 and intrapulmonary shunt in the patients with ARDS, while it had little effect on the patients with infectious pulmonary disease or COPD. The infusion of fat emulsion had positive effects on the patients with normal lung condition with increased PaO2/FIO2 and decreased P(A-a)O2 and shunt. PMID- 2108850 TI - Bleeding time and other laboratory tests to monitor the safety and efficacy of thrombolytic therapy. AB - Widespread use of thrombolytic agents in a variety of settings has highlighted the need for measures of safety and efficacy. Previously used laboratory parameters, such as decreasing levels of fibrinogen and increasing levels of fibrin(ogen) degradation products (FDPs), have failed to correlate consistently with hemorrhagic events and have not yet been useful in predicting patients at risk for bleeding. Although the bleeding time (BT) has been considered primarily to reflect platelet function, it also reflects the interaction of platelets with vessel wall and coagulation pathways. Recently, the BT has been considered as a potential predictor of clinical bleeding during thrombolysis. The BT, as a measure of in vivo hemostatic competence, may be particularly well-suited for this application. Serial BTs during thrombolytic therapy may provide valuable information regarding safety and efficacy, but further studies are needed to confirm preliminary findings. PMID- 2108851 TI - Thrombolytic therapy in acute myocardial infarction. AB - Recombinant tissue-type plasminogen activator (rt-PA), streptokinase (SK), and anisoylated plasminogen-streptokinase activator complex (APSAC) have salutary effects on mortality when administered to patients with evolving acute myocardial infarction (MI). Studies suggest that intravenous rt-PA is more effective in reperfusing occluded infarct-related arteries than SK, and the results of ongoing studies directly comparing the influence of SK and rt-PA on mortality are awaited. The clinical role of agents such as APSAC, urokinase, and pro-urokinase, used alone or in combination, remains to be determined. It is evident that a variety of thrombolytic agents will be effective, and variables such as ease of administration, pharmacokinetics, fibrin specificity, effects on blood viscosity, and incidence of adverse effects need to be assessed to determine which agents are the most suitable for clinical use. There is an increased risk of bleeding at vascular puncture sites with all thrombolytic agents. Current indications for thrombolytic therapy include ischemic chest pain of at least 30 min duration that is unrelieved by nitroglycerin and is associated with ST-segment elevations of at least 0.1 mV in two contiguous electrocardiographic leads. Such therapy is usually reserved for patients less than 75 years old who are not at increased risk for bleeding and whose chest pain began less than 4-6 prior to treatment. Trials are under way to determine whether patients with shorter pain duration, transient ST-segment changes (ie, unstable angina patients), chest pain associated with ST-segment depressions or T-wave inversions (ie, non-Q-wave infarction patients), or patients whose pain began more than 4 to 6 h earlier will benefit from early thrombolytic therapy. Other factors such as patient age, the likelihood of the diagnosis of MI, and the estimated risk of bleeding should also be considered. The findings of available major randomized trials indicate that early invasive procedures are generally unnecessary and that meticulous care must be exercised in the selection and management of patients subjected to thrombolytic therapy. PMID- 2108852 TI - Role of aspirin with thrombolytic therapy in acute myocardial infarction. AB - Thrombolytic therapy has been shown to limit infarct size, improve ventricular function, and decrease mortality in suspected evolving myocardial infarction (MI). Aspirin therapy also decreases mortality as well as stroke and reinfarction in suspected evolving MI. The combined ability of both agents to lyse as well as to prevent clots yields a greater benefit than either alone. The use of aspirin with thrombolysis also protects against the increase in reinfarction observed when thrombolytic therapy is given alone. While ongoing research is evaluating the optimal thrombolytic agent as well as the possible role of heparin, it is already clear that the use of aspirin with thrombolytic therapy will significantly decrease reinfarction, stroke, and vascular mortality in suspected evolving MI. PMID- 2108853 TI - Rationale for bolus t-PA therapy to improve efficacy and safety. AB - Tissue-type plasminogen activator has high affinity for fibrin and is activated by fibrin. Because of these properties, t-PA was initially expected to cause minimal bleeding complications. This prediction has been only partially confirmed in major clinical trials in which t-PA was given in the doses necessary for effective coronary thrombolysis. The risk of bleeding in patients receiving t-PA is correlated with increased levels of fibrin degradation products and hypofibrinogenemia, consistent with a link between systemic plasminemia and hemorrhage. Limiting t-PA-associated bleeding may therefore require measures aimed at decreasing hyperplasminemia. These measures include a short infusion of a high t-PA dose. This article presents new experimental evidence that has confirmed our previous results showing that a short infusion of t-PA is an effective and safe thrombolytic treatment. PMID- 2108854 TI - A new short infusion dosage regimen of recombinant tissue plasminogen activator in patients with venous thromboembolic disease. AB - Although recombinant tissue-type plasminogen activator (rt-PA) has the potential to induce thrombolysis without producing a generalized coagulopathy, the dosage regimens in present use induce a plasma fibrinolytic state and are associated with bleeding. Animal experiments have demonstrated that rt-PA produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is increased and bleeding is reduced when rt-PA is administered over a short time period. To determine whether a short course regimen of rt-PA has potential in man, we gave a bolus injection of rt-PA (0.6 mg/kg) concurrently with heparin to five patients with venous thromboembolism. Three patients with angiographically proven pulmonary embolism had marked improvement of the perfusion defects when lung scans were repeated 24 h after rt-PA administration. In one of two patients with thrombosis of the deep veins of the upper extremity the venographic defect resolved completely. In three of four patients there was a mild decrease in fibrinogen and a moderate decrease in alpha 2-antiplasmin levels. There was no excessive bleeding. These results suggest that a bolus injection regimen of rt-PA has considerable potential in the treatment of thromboembolic disease. PMID- 2108855 TI - Tissue plasminogen activator (rt-PA) vs heparin in deep vein thrombosis. Results of a randomized trial. AB - We performed a randomized trial comparing two dosing regimens of recombinant tissue plasminogen activator (rt-PA) plus heparin vs heparin alone in the treatment of acute proximal deep vein thrombosis in 83 patients. Of 12 patients who received 0.5 mg/kg rt-PA plus heparin over 4 h, seven (58 percent) had greater than 50 percent lysis of the thrombus, compared with none of 12 who received placebo plus heparin (p = 0.002). Of 28 patients who received 0.5 mg/kg rt-PA over 8 h, repeated in 24 h, six (21 percent) had greater than 50 percent lysis, compared with two (7 percent) of 30 patients who received placebo plus heparin (p = 0.11). The 4-h infusion of rt-PA produced a 40 percent reduction and the 8-h infusion an 11 percent reduction in plasma fibrinogen concentration. At long-term follow-up, three (25 percent) of 12 patients in whom greater than 50 percent lysis was achieved had symptoms of the postphlebitic syndrome, compared with 19 (56 percent) of 34 patients in whom lysis was less than 50 percent (p = 0.07). PMID- 2108856 TI - Thrombolysis in venous thromboembolism. An international perspective. AB - Two promising novel recombinant tissue-type plasminogen activator (rt-PA) regimens for pulmonary embolism (PE) are being actively investigated: 100 mg/2 h as a continuous peripheral intravenous infusion, and bolus rt-PA, adjusted to weight, as a 2-min infusion. For deep venous thrombosis (DVT), less progress has been made in finding an optimal dosing regimen of rt-PA. Our mandate for the 1990s is to use the best possible thrombolytic dosing regimens in large clinical trials of PE and DVT. The primary objective of these planned clinical studies is to determine which patients with PE and DVT will benefit the most from thrombolysis followed by anticoagulation rather than anticoagulation alone. PMID- 2108857 TI - Modulation of the frequency of glucose-dependent bursts of electrical activity by HCO3/CO2 in rodent pancreatic B-cells: experimental and theoretical results. AB - The burst pattern of electrical activity recorded from pancreatic B-cells in response to 11 mM glucose shows a large islet to islet variability. The relationship between burst frequency and glucose sensing (the threshold for electrical activity and the graded increase in electrical response to glucose, i.e. active phase %) has not been investigated within the same islet. In this work, we show that low HCO3 (5 mM) Hepes buffered solutions reversibly reduce the frequency of bursts compared to control (25 mM) HCO3 buffered solutions in the same islet. There was no change in the threshold or active phase (%). Using the mathematical model of Sherman et al. 1988, we explored mechanisms for a change in frequency independent of a change in active phase (%). Increased exchangeable calcium pool size and increased cell to cell coupling were the two theoretical treatments which could reproduce the experimental data. We conclude that burst frequency can be modulated independent of the active phase and that alteration of a calcium pool size best fits the experimental data. PMID- 2108858 TI - The amino acid sequence of the CCGG recognizing DNA methyltransferase M.BsuFI: implications for the analysis of sequence recognition by cytosine DNA methyltransferases. AB - The Bacillus subtilis FI DNA methyltransferase (M.BsuFI) modifies the outer cytosine of the DNA sequence CCGG, causing resistance against R.BsuFI and R.MspI restriction. The M.BsuFI gene was cloned and expressed in B.subtilis and Escherichia coli. As derived from the nucleotide sequence, the M.BsuFI protein has 409 amino acids, corresponding to a molecular mass of 46,918 daltons. Including these data we have compared the nucleotide and amino acid sequences of different CCGG recognizing enzymes. These analyses showed that M.BsuFI is highly related to two other CCGG specific methyltransferases, M.MspI and M.HpaII, which were isolated from Gram-negative bacteria. Between M.BsuFI and M.MspI the sequence similarity is particularly significant in a region, which has been postulated to contain the target recognition domains (TRDs) of cytosine-specific DNA methyltransferases. Apparently M.BsuFI and M.MspI, derived from phylogenetic distant organisms, use highly conserved structural elements for the recognition of the CCGG target sequence. In contrast the very same region of M.HpaII is quite different from those of M.BsuFI and M.MspI. We attribute this difference to the different targeting of methylation within the sequence CCGG, where M.HpaII methylates the inner, M.BsuFI/M.MspI the outer cytosine. Also the CCGG recognizing TRD of the multispecific B.subtilis phage SPR Mtase is distinct from that of the host enzyme, possibly indicating different requirements for TRDs operative in mono- and multispecific enzymes. PMID- 2108859 TI - Structure of the gene of tum- transplantation antigen P35B: presence of a point mutation in the antigenic allele. AB - Mutagen treatment of P815 tumour cells produces tum- variants that are rejected by syngeneic mice because they express new transplantation antigens. These 'tum-' antigens elicit a cytolytic T lymphocyte (CTL) response but no detectable antibody response. The DNA of tum- variant P35 was transfected into P815 cell line P1.HTR. Transfectants expressing tum- antigen P35B were identified on the basis of their ability to stimulate anti-P35B CTL. This was repeated with a cosmid library and a cosmid carrying the sequence encoding antigen P35B was recovered from a transfectant expressing the antigen. Gene P35B is 6 kb long and contains 11 exons. The sequence shows no homology with the previously identified tum- gene P91A nor with any gene presently recorded in the data banks. The antigenic allele of gene P35B differs from the normal allele by a point mutation located in exon 5. This mutation, which replaces a Ser by an Asn residue, was shown by site-directed mutagenesis to be responsible for the expression of the antigen. A synthetic decapeptide covering the sequence surrounding the tum- mutation rendered P815 cells sensitive to lysis by anti-P35B CTL. Surprisingly, the homologous peptide corresponding to the normal sequence of the gene had the same effect, indicating that this tum- mutation does not exert its effect by generating the aggretope or the epitope of the antigenic peptide. As observed previously with gene P91A, we found that fragments of gene P35B containing only exons 4 and 5, which were cloned in non-expression vectors, transferred efficiently the expression of the antigen. PMID- 2108860 TI - Antibody domain mutants demonstrate autonomy of the antigen binding site. AB - We have constructed derivatives of a lambda I light chain-bearing anti-(4 hydroxy,3-nitrophenyl)acetyl (NP) antibody which have the V regions exchanged between heavy chains and light chains of the kappa or lambda I type. These antibodies are assembled and secreted normally, and bind haptenic and macromolecular ligands like the wild-type; similar results are obtained for monovalent heterodimers of VHCL and lambda I light chains. The observed independence of the binding site from the constant region context argues against a role of longitudinal interactions between constant and variable domains in antigen recognition, and therefore against cooperativity between binding sites. PMID- 2108861 TI - In vivo transformation of factor-dependent hemopoietic cells: role of intracisternal A-particle transposition for growth factor gene activation. AB - Cells of the granulocyte-macrophage colony stimulating factor (GM-CSF) or multi lineage colony stimulating factor (Multi-CSF) dependent line FDC-P1 undergo leukemic transformation after injection into irradiated DBA/2 mice. About one third of factor-independent FDC-P1 variants isolated from leukemic animals express GM-CSF or Multi-CSF, assessed either by bioassay or by sensitive RNA detection using the polymerase chain reaction. All of the GM-CSF-secreting lines studied had a rearrangement in one allele of the GM-CSF gene, three of four Multi CSF-secreting lines had Multi-CSF gene rearrangements, while factor-independent lines lacking evidence of growth factor production had no demonstrable CSF gene alterations. All rearrangements were characterized by insertions of novel DNA in the 5'-flanking regions of the CSF genes. The inserted segments of DNA varied in size between 0.35 and 6.5 kb and displayed restriction enzyme cleavage maps reminiscent of intracisternal A-particle (IAP) genomes. This was confirmed in two cases by molecular cloning and nucleotide sequence analysis. In these instances, the insertion consisted of solitary IAP long terminal repeats. The transformation system described provides a model for the study of IAP transpositions and their effects on gene activation. PMID- 2108862 TI - Synergistic interaction between interferon-alpha and interferon-gamma through induced synthesis of one subunit of the transcription factor ISGF3. AB - Interferon-alpha (IFN alpha) and interferon-gamma (IFN gamma) each induce in susceptible target cells a state of resistance to viral replication and reduced cellular proliferation, presumably through different mechanisms: these two polypeptides are unrelated by primary sequence and act through distinct cell surface receptors to induce expression of largely non-overlapping sets of genes. However, acting in concert, they can produce synergistic interactions leading to mutual reinforcement of the physiological response. In HeLa cells, this synergistic response was initiated by cooperative induction of IFN alpha stimulated genes (ISGs). These normally quiescent genes were rapidly induced to high rates of transcription following exposure of cells to IFN alpha. Although they were only negligibly responsive to IFN gamma, combined treatment of cells with IFN gamma followed by IFN alpha resulted in an approximately 10-fold increase in ISG transcription. ISG transcription is dependent upon ISGF3, a positive transcription factor specific for a cis-acting regulatory element in ISG promoters. IFN gamma treatment induced increased synthesis of latent ISGF3, which was subsequently activated in response to IFN alpha to form approximately 10-fold higher levels than detected in cells treated with IFN alpha alone. ISGF3 is composed of two distinct polypeptide components, synthesis of one of which was induced by IFN gamma, increasing its cellular abundance from limiting concentrations to a level which allowed formation of at least 10 times as much active ISGF3. Cell lines vary in their constitutive levels of the inducible component of ISGF3 and in the ability of IFNs to increase its synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108865 TI - Generation of platelet activating factor (PAF) by a human lung epithelial cell line. AB - A human lung epithelial cell line (ATC-CCL-185) was cultured in nutrient Ham-F12 medium. Cells in monolayers were stimulated with either ionophore A23187 (1 microM) or phorbol myristate acetate (PMA, 0.2 microM) for various periods of time. Samples were analysed by HPLC and the presence of platelet activating factor (PAF) was detected by bioassay of the release of [3H]serotonin from rabbit platelets undergoing aggregation. The ATC-CCL 185 cells were found to synthesize PAF following activation with either PMA or ionophore. Ionophore at 1 microM was found to be more potent than PMA at 0.2 microM in the induction of PAF synthesis (congruent to 80 ng/mg protein). The synthesis of PAF through ionophore stimulation reached a maximum at 5 min, whereas PMA stimulation peaked at 15-20 min. PMA induced approximately one third the level of PAF synthesis by the ionophore. The PAF synthesized by these CCL185 cells was found to be mainly associated with the cell membrane with less than 10% released into the medium. Release of PAF into cell supernatant was dependent on the presence of bovine serum albumin (BSA). In the absence of BSA, a large portion (approximately 90%) of PAF was found to be cell associated, and only 60% when BSA concentration reached greater than or equal to 0.2%. These results demonstrate the ability of this lung epithelial cell line to synthesis PAF thus, suggesting that epithelial cells might participate in the process of inflammatory lung diseases, through the generation of this important mediator. PMID- 2108863 TI - Synergism in ternary complex formation between the dimeric glycoprotein p67SRF, polypeptide p62TCF and the c-fos serum response element. AB - Transcriptional regulation of the c-fos proto-oncogene requires the serum response element (SRE) which is complexed by a multi-protein assembly observed both in vitro and in vivo. Two protein factors, p67SRF and p62TCF (previously called p62), are required to interact with the SRE for efficient induction of c fos by serum. By quantitative band shift electrophoresis we measure at least a 50 fold increase in SRE affinity for p67SRF/p62TCF over p67SRF alone. Stoichiometrically we determine that the ternary complex with p62TCF involves p67SRF in dimeric form. We demonstrate that p67SRF is a glycosylated nuclear transcription factor carrying terminal N-acetylglucosamine (GlcNAc) as a post translational modification. A proteolytic limit digestion product, approximately 13 kd in size, was generated from the p67SRF-SRE complex. This p67SRF-core domain binds SRE, can dimerize with p67SRF and is still able to form a ternary complex with p62TCF. Therefore, three functional activities can be ascribed to this small p67SRF-core domain: specific DNA binding, dimerization and interaction with p62TCF. We demonstrate that these functions map within the p67SRF core fragment containing the region between amino acids 93 and 222. PMID- 2108864 TI - Glutactin, a novel Drosophila basement membrane-related glycoprotein with sequence similarity to serine esterases. AB - Glutactin, a new acidic sulfated glycoprotein, was isolated from Drosophila Kc cell culture media. Immunofluorescence microscopy located it to embryonic basement membranes, particularly to the sequentially invaginated envelope of the central nervous system, muscle apodemes and dorsal median cell processes. Its chromosome locus is 29D. The nucleic acid sequence coding for the 1023 residue long polypeptide contains one intron and was confirmed by partial amino acid sequencing. Glutactin has a signal peptide and an amino domain of greater than 500 residues that strongly resembles acetylcholine esterases and other serine esterases, but lacks the catalytically critical serine residue. The amino and carboxyl domains of glutactin are separated by 13 contiguous threonine residues. Glutamine and glutamic acid make up 44% of glutactin's very acidic carboxyl domain. Glutactin preferentially binds Ca2+ in the presence of excess Mg2+ and four of its tyrosines are O-sulfated. Several similarities with mammalian entactin caused our previous, preliminary mention of glutactin as a putative Drosophila entactin, but sequence comparison now shows them to be different proteins. PMID- 2108866 TI - Effects of H-7 (protein kinase inhibitor) and phorbol ester on aortic strips from spontaneously hypertensive rats. AB - We investigated the vascular responsiveness to vasoactive agents and the inhibition by H-7 (1-(5-isoquinoline-sulfonyl)-2-methylpiperazine), which inhibits cyclic nucleotide-dependent protein kinases and protein kinase C(PKC) equally potently in helically cut strips of thoracic aortas from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The susceptibility of norepinephrine (NE)- and angiotensin II (Ang II)-induced contractions to H-7 was significantly higher in the aortas from SHR than in those from WKY. H-7 decreased the contractile responses to KCl to a similar extent in both strains without affecting the high K(+)-stimulated Ca2+ influx. H-7 produced a shift to the right of the dose-response curve for the PKC activator, 12-o tetradecanoylphorbol-13-acetate (TPA) in the case of SHR aortas, while no such shift was noted in tissues from WKY. Functional alterations in the PKC branch of the Ca2+ messenger system in vascular smooth muscle may play an important role in SHR during the sustained contraction. PMID- 2108867 TI - Effect of diltiazem on spontaneous cyclic Ca2+ release from sarcoplasmic reticulum. AB - We used saponin-treated skinned fibers isolated from papillary muscles of the right ventricle of guinea pigs to compare the effects of diltiazem on the spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum (SR) of cardiac muscle with the effects of caffeine. Both diltiazem and caffeine increased the frequency of cyclic contractions in EGTA (ethyleneglycol-bis-(beta aminoethylether) N,N,N',N'-tetra-acetate)-free solution and induced an incomplete, concentration-dependent relaxation of the muscle. The results suggest that the spectrum of the pharmacological effects of diltiazem on the SR is similar to that for caffeine, that is diltiazem accelerates the spontaneous Ca2+ release from the SR and suppresses Ca2+ reuptake by the SR, and that diltiazem as well as caffeine may act on the SR in vivo in a specific condition. PMID- 2108868 TI - Effects of MCI-154, a novel cardiotonic agent, on mean circulatory filling pressure in anesthetized dogs. AB - The effects of MCI-154, a novel cardiotonic agent, on mean circulatory filling pressure (an index of total body venous tone), total peripheral resistance and the heart were examined in anesthetized dogs. The bolus injection of MCI-154 (10 100 micrograms/kg i.v.) caused a dose-dependent decrease in mean circulatory filling pressure and resistance to venous return. MCI-154 also decreased the mean blood pressure and total peripheral resistance, and increased cardiac output and heart rate. Right atrial pressure was reduced only by the lowest dose (10 micrograms/kg i.v.) of MCI-154. These hemodynamic effects of MCI-154, except those on mean circulatory pressure and resistance to venous return, reached a maximum with 30 micrograms/kg of the drug. Nitroglycerin (50 micrograms/kg i.v.), a venodilator, decreased mean circulatory filling pressure, resistance to venous return, mean blood pressure and total peripheral resistance, and increased heart rate. However, unlike MCI-154, nitroglycerin did not alter cardiac output and right atrial pressure. These results suggest that the venodilator effect of MCI 154, as well as the positive inotropic and vasodilator effects, could potentially benefit patients with congestive heart failure. PMID- 2108869 TI - Human listeriosis in Britain, 1967-85, a summary of 722 cases. 1. Listeriosis during pregnancy and in the newborn. AB - Clinical information was collected on 722 cases of Listeria monocytogenes infections in humans occurring in Britain between 1967 and 1985: 248 cases (34%) were associated with pregnancy (maternal, foetal, and neonatal), and comprised 9 cases (4%) of maternal bacteraemia without infection of the foetus; 42 cases (19%) of intra-uterine deaths; 118 cases (54%) of neonatal infection diagnosed within 2 days post-partum; and 50 cases (23%) of neonatal infection diagnosed as ill after 2 days post-partum. An overall mortality of 50% was recorded. The cases unassociated with pregnancy are described elsewhere (see accompanying paper). PMID- 2108871 TI - A competitive ELISA for the detection of group-specific antibodies to African horse sickness virus. AB - A competition enzyme-linked immunosorbent assay (ELISA) has been developed for the rapid identification and quantification of antibodies against African horse sickness (AHS) in sera from solipeds. The data showed the ELISA to be sensitive, specific and reliable. More than 1600 sera from 37 different countries were examined and results compared with those obtained by agar gel immuno-diffusion (AGID) tests. In no case did any of 775 sera from countries where AHS has never been reported and where AHS vaccines are not used, record an ELISA titre greater than 4. A titre equal to or greater than 8 was considered positive. Using this criterion, 96.3% of sera tested in both assays were in agreement. Doubtful results by AGID (1.7%) were clearly defined in terms of positivity and negativity by ELISA. This ELISA is suited for the rapid laboratory confirmation of AHS and should be considered as a replacement for the traditional AGID test. PMID- 2108870 TI - Human listeriosis in Britain, 1967-85, a summary of 722 cases. 2. Listeriosis in non-pregnant individuals, a changing pattern of infection and seasonal incidence. AB - Clinical information was collected on 722 cases of Listeria monocytogenes infections in humans occurring in Britain between 1967 and 1985. This series comprised 34% (248 cases) associated with pregnancy and 66% (474 cases) in non pregnant adults and juveniles. The cases not associated with pregnancy comprised: 76% in patients with severe underlying illness (of which 34% had central nervous system infections, and 42% bacteraemia without involvement of the central nervous system); 21% in previously healthy individuals (of whom 18% had meningitis); and 3% in patients without bacteraemia or involvement of the central nervous system. Cases occurred most often in male patients over 40 years of age. The overall mortality was 44%. Overall, the pattern of infection has altered to a disease of higher incidence, affecting most often susceptible non-pregnant individuals and the unborn. An annual increase in incidence of listeriosis occurred in the autumn in all categories of patients. PMID- 2108872 TI - Cytosolic calcium mobilization and thromboxane synthesis in a human megakaryocytic leukemia cell. AB - The functional and biochemical characteristics of human megakaryocytic leukemia cells remain unclear. In this study, we examined cytosolic Ca2+ ([Ca2+]i) mobilization and thromboxane (TX) formation in a megakaryocytic leukemia cell line, designated CMK. Stimulation of CMK cells with thrombin resulted in an increase of [Ca2+]i as measured with the fluorescent marker Fura 2-AM. The rise in [Ca2+]i was mostly dependent on extracellular Ca2+. Prostaglandin E1 (PGE1) further increased [Ca2+]i after thrombin addition, thus indicating that PGE1 had a different action on [Ca2+]i in cells of the platelet-megakaryocyte lineage. The addition of thrombin and the calcium ionophore A23178 to CMK cells caused similar rapid formations of TXB2 as measured by RIA. Thrombin plus A23178 had a synergistic effect on TXB2 synthesis in CMK cells. Thrombin had no effect of TX metabolism in the cells with myeloid, erythroid, B-lymphoid, and T-lymphoid lineages. These results indicate that thrombin-induced TX synthesis may serve as a marker of immature megakaryocytes. PMID- 2108873 TI - Morphological classification and retinal distribution of large ganglion cells in the retina of Bufo marinus. AB - The retrograde transport of horseradish peroxidase (HRP) and cobaltic-lysine complex (CLC) was used to morphologically characterize large ganglion cells (GCs) and to determine their distribution in retinal wholemounts and in sectioned material in the retina of Bufo marinus. Large GCs, amounting to about 0.5% of total GC population, were defined to be those with very large dendritic field sizes varying between 0.1 mm2 to 0.6 mm2 and cell soma sizes of between 100 microns 2 to 400 microns 2. These cells were subdivided into 3 major groups, Types I, II and III, on the basis of their dendritic field sizes, aborization patterns and the strata of dendritic branching within the inner plexiform layer (IPL). The majority of large neurons (about 90%) were classified as Type I GCs with symmetrical dendritic arbor. These cells had either bistratified branching in the scleral and vitreal sublamina of the IPL (65% of Type I Cells) or unistratified branching in the scleral (26%) or in the vitreal (9%) sublamina. Their dendritic field sizes increased linearly from the retinal centre from 0.13 mm +/- 0.02 mm2 (mean and S.D.) to 0.58 +/- 0.11 mm2 in the retinal periphery. Type II GCs (about 9% of large GC population) were characterized by an asymmetrical dendritic aborization directed towards the ciliary margin with unistratified branching in the scleral sublamina of the IPL. The mean dendritic field sizes of these cells were 0.26 +/- 0.09 mm2. Type III GCs, the least frequent (about 1%) category of large GCs had sparsely branching, elongated dendritic branching aligned approximately parallel with the nasotemporal axis of the retina. The unistratified dendritic branches of these neurons were located in the vitreal sublamina of the IPL with a mean dendritic field size of 0.42 +/- 0.11 mm2. The dendritic field sizes of Types II and III GCs did not increase with retinal eccentricity. Type I GCs were distributed unevenly across the retina, the density being greatest in the visual streak, along the nasotemporal meridian of the retina. The dendritic field sizes of these cells increased towards the retinal periphery, resulting in a constant dendritic field coverage factor across the retina. Each retinal point was covered by the dendritic fields of 4-5 adjacent GCs. In contrast, Types II and III GCs had only discontinuous dendritic coverage. The identification of morphological types of large GCs with previously described functional classes of GCs in the anuran retina is discussed. PMID- 2108874 TI - The use of a retroviral vector to identify foetal striatal neurones transplanted into the adult striatum. AB - A retrovirus which encodes beta-galactosidase was used to infect embryonic rat striatal cells before grafting these cells into the lesioned adult rat striatum. Examination of the grafts after long term survival (8 months) revealed that a few small and large cells expressed large amounts of bacterial beta-galactosidase activity. The larger diameter cells were identified as neurones by their size, shape and presence of neuronal processes. The identity of the small diameter cell types was not established. PMID- 2108875 TI - Leptopilina heterotoma and L. boulardi: strategies to avoid cellular defense responses of Drosophila melanogaster. AB - Eggs of three strains of the cynipid parasitoid Leptopilina heterotoma and a Tunisian strain (G317) of L. boulardi are not encapsulated by hemocytes of Drosophila melanogaster hosts, but the eggs of a Congolese strain (L104) of L. boulardi are encapsulated. To determine the reason for the difference in host response against the parasitoid eggs, lamellocytes (hemocytes that encapsulate foreign objects and form capsules around endogenous tissues in melanotic tumor mutants) were examined in host larvae parasitized by the five Leptopilina strains. Parasitization by the three L. heterotoma strains affected the morphology of host lamellocytes and suppressed endogenous melanotic capsule formation in melanotic tumor hosts. L104 did not alter the morphology of host lamellocytes nor block tumor formation in melanotic tumor mutant hosts. The morphology of some lamellocytes was affected by G317 parasitization but host lamellocytes were still capable of forming melanotic tumors and encapsulating dead supernumerary parasitoid larvae. Therefore, the eggs of strains affecting lamellocyte morphology are protected from encapsulation by the host's blood cells. L. heterotoma eggs float freely in the host hemocoel but L. boulardi eggs are attached to host tissue surfaces. Lamellocytes cannot infiltrate the attachment site so the capsule around the L104 egg remains incomplete. The wasp larva uses this gap in the capsule as an escape hatch for emergence. PMID- 2108876 TI - DNA probe diagnosis of parasitic infections. PMID- 2108877 TI - Public-sector savings resulting from expenditures for contraceptive services. AB - Almost one in four U.S. women who use a reversible method of contraception rely on a publicly funded source of care, either a family planning clinic or a private physician reimbursed by Medicaid. According to three scenarios of alternative contraceptive use patterns, if publicly funded services were not available, these women would have between 1.2 million and 2.1 million unintended pregnancies over one year--substantially more than the approximately 400,000 they currently experience. If these women relying on publicly funded services were using no method of contraception, they would be expected to have more than 3.5 million unintended pregnancies in one year. In FY 1987, federal and state governments spent $412 million on contraceptive services for women who otherwise might not have been able to obtain them. If these services had not been available, the additional public costs for medical care, welfare and supplementary nutritional programs during the first two years after a birth or for publicly funded abortions would have totaled $1.2-$2.6 billion. These savings represent an average of $4.40 saved for every dollar of public funds spent to provide contraceptive services. PMID- 2108879 TI - [Use of the carbon dioxide laser in the treatment of leukoplakia]. AB - Experiences obtained in the course of laser surgical treatment of 126 mouth cavity leukoplakias are summarized. The elaborated, differentiated method ensures, besides safe removal of tissues infected by leukoplakia, a possibility for significantly preserving the functions of the mouth cavity. In case of simplex leukoplakia coagulation by means of defocused laser beam of 5 W energy, in case of verrucosus vaporization by means of focused beom of 10 to 15 W, and in erosiv cases excision in carried out by means of focused beom of 20 to 25 W energy. After laser treatment out of 126 patients 118 were free of symptoms. After operation emberging pain, oedema are minimal. (As a rule, the patients are capable of work the other day.) It is stated that the leucoplakias represent one of the most important fields of the oral surgical employment of the CO2 laser beam. PMID- 2108878 TI - [Age-related characteristics of the effect of periodic low-calorie nutrition on lipid composition of the liver cells, small intestine, adipose tissue and blood serum in albino rats]. AB - It is studied how long-term periodical calorie-insufficient and growth restraining nutrition promoting appreciable life prolongation in the Wistar-line albino rats influences the lipid metabolism. It is shown that diet has an essential influence on the levels of phospholipids, cholesterol, neutral lipids, fatty acids in different tissue cells. The age specificity is observed in all the studied tissue cells. The lipid composition of cells in aged rats with prolonged life is similar to that of young animals of control group. PMID- 2108880 TI - Diabetic retinopathy: a physician's view. PMID- 2108881 TI - Clinical progress with LHRH analogues in prostatic cancer. Proceedings of an international symposium. Monte Carlo, 20 January 1990. PMID- 2108882 TI - 3.75 and 7.5 mg leuprorelin acetate depot in the treatment of advanced prostatic cancer: preliminary report. German Leuprorelin Study Group. AB - In an on-going, non-comparative, open, multicentre phase III study in Germany, 190 patients with advanced prostatic cancer were treated with 3.75 or 7.5 mg leuprorelin acetate depot given subcutaneously or intramuscularly once monthly, with or without concomitant antiandrogen or cytostatic therapy. The two doses and the different routes of administration did not have any significant effects on serum testosterone, dihydrotestosterone, follicle stimulating hormone and luteinizing hormone concentrations, tumour activity or clinical tolerance. Using either dose, the 'no progression' rate (complete remission plus partial remission plus stable disease) was 88.5% overall and was 88.2% in T1-T2 disease and 82.5% in T3-T4 disease after 12 months' treatment. It is concluded that the depot formulation of leuprorelin acetate offers an important alternative in the treatment of advanced prostatic cancer. PMID- 2108883 TI - Leuprorelin acetate depot in advanced prostatic cancer: a phase II multicentre trial. AB - The therapeutic efficacy and safety of various doses of leuprorelin acetate depot were determined in an open, multicentre study of patients with locally advanced or metastatic prostatic cancer (stages C, D1 or D2). Patients were randomly assigned to receive 3.75 mg (30 cases), 7.5 mg (eight cases), 15 mg (eight cases) and 30 mg (one patient) leuprorelin acetate depot administered subcutaneously once every 4 weeks. Of the 43 patients evaluable, two (5%) had complete remission, 23 (53%) partial remission and 13 (30%) patients stable disease. No significant differences were observed in response rates in relation to dose, disease stage or previous hormonal therapy. Disappearance or improvement in bone pain and urinary symptoms occurred in 63% and 79% of cases, respectively. Serum androgen concentrations decreased rapidly and persistently to castration levels, without significant differences for different doses. Treatment was well tolerated with a low incidence of mild side-effects - gynaecomastia (16%), nausea/vomiting (13%) and diarrhoea (2%). It is concluded that 3.75 mg leuprorelin acetate depot given subcutaneously once every 4 weeks is able to produce hormonal effects in all patients, an overall objective response comparable to that obtained using higher doses. PMID- 2108884 TI - Luteinizing hormone releasing hormone agonists: the US experience. AB - In a large multicentre trial, 1 mg/day leuprorelin given subcutaneously was as effective as diethylstilboestrol in the treatment of prostatic cancer but with a lower incidence of side-effects, although leuprorelin could induce tumour flare up. Total androgen ablation using a combination of leuprorelin and the non steroidal anti-androgen flutamide in the treatment of prostatic cancer was more effective than either orchidectomy or diethylstilboestrol. The efficacy of 1 mg/day leuprorelin given subcutaneously plus 250 mg flutamide three times a day compared with leuprorelin plus placebo was confirmed in a randomized, double blind study of 603 patients. Progression-free and overall survival were prolonged, and tumour flare-up and other side-effects were reduced in patients with untreated advanced prostatic cancer and in those with minimal disease. PMID- 2108885 TI - Human pharmacokinetic and pharmacodynamic profiles of leuprorelin acetate depot in prostatic cancer patients. AB - A total of 21 patients with advanced prostatic cancer and one patient with benign prostatic hypertrophy received 3.75, 7.5 or 15 mg leuprorelin acetate depot subcutaneously. Serum leuprorelin concentrations increased immediately after injection, reaching a peak concentration (range 13.1-54.5 ng/ml), which was directly proportional to dose, within 3 h. Mean drug levels subsequently declined to a plateau directly proportional to dose at 5 weeks. There was also a significant (P less than 0.01) dose-dependent increase in the area under the concentration-time curve for 0-35 days. Serum concentrations of luteinizing hormone and follicle stimulating hormone rose initially with all doses, followed by a rise in serum testosterone and dihydrotestosterone concentrations, which then fell sharply, within 3 weeks. A reduced level of follicle stimulating hormone subsequently occurred in all 20 evaluable patients and was maintained in 17 patients over 5 weeks. There was also marked initial suppression of luteinizing hormone levels in 15 patients and in 13 this continued. Castration levels of testosterone and dihydrotestosterone were maintained in all patients for up to 5 weeks. In two patients there was a complete response, in 14 a partial response and in three stable disease, with no significant differences in relation to dose. Clinical improvement and serum hormonal changes suggest that leuprorelin acetate depot is effective at a dose as low as 3.75 mg when given once every 4 weeks. PMID- 2108886 TI - Clinical efficacy and safety of a new leuprorelin acetate depot formulation in patients with advanced prostatic cancer. AB - A depot preparation of leuprorelin acetate was assessed in 52 patients with advanced prostatic cancer. Patients received 3.75 mg, or occasionally 7.5 mg, leuprorelin acetate depot subcutaneously every 28 +/- 3 days for up to 2 years. Following treatment, there was one complete remission and 29 partial remissions; in other patients the disease was stable and in five it was progressive, with an estimated median time to progression of 500 days. Significant improvement in performance status, micturition problems and general well-being were reported. Suppression of serum testosterone and luteinizing hormone concentrations was maximal after 28 days and castration levels were maintained for up to 96 weeks. Tumour flare occurred in 15 (29%) patients during the first week of therapy but only one event was serious; sweating and flushing also occurred occasionally during the study. Of all administrations, 97% were free from any adverse local effect, the remaining events being mild in severity. It is concluded that once monthly administration of leuprorelin acetate depot is effective in the management of advanced prostatic cancer and has an acceptable side-effect profile. PMID- 2108887 TI - Preliminary clinical evaluation of leuprorelin acetate depot injection in France, in the management of prostatic cancer. AB - In a preliminary multicentre clinical trial of 3.75 mg leuprorelin acetate depot 18 previously untreated patients with metastatic prostatic cancer were treated with the depot given subcutaneously once every 4 weeks for 28 weeks. Patients also received 100 mg nilutamide taken orally three times a day for the first 14 days of treatment to prevent flare-up. Leuprorelin acetate suppressed the serum testosterone concentration to castration levels; luteinizing hormone levels were also suppressed. The incidence of progressive disease was low and partial response occurred in five patients after treatment. No side-effects were assigned to the flare-up period. It is concluded that leuprorelin acetate depot is a safe and efficacious treatment for metastatic prostatic cancer. PMID- 2108888 TI - Clinical experience with leuprorelin acetate before radiotherapy for prostatic cancer. AB - A total of 40 patients with stages A2 to C prostatic cancer were treated with leuprorelin acetate depot once a month for 2 months before being treated by pelvic irradiation or radical prostatectomy. In the 32 patients who were evaluable, seven (22%) were classified as minor responders after leuprorelin treatment and 23 (72%) as major responders when assessed by rectal examination. Prostate-specific antigens also returned to normal concentrations (5 ng/ml) in 26/31 (84%) patients. Leuprorelin acetate depot suppressed plasma testosterone concentrations to castration values during treatment, but concentrations returned to normal 2 months after completion of treatment. Following radical treatment, there were three deaths--one postoperative and two due to recurrent disease--but there was no isolated local relapse. It is concluded that the protocol was locally well tolerated and was effective in the treatment of stages B2 and C prostatic cancer patients. PMID- 2108889 TI - Leuprorelin acetate depot: results of a multicentre Japanese trial. TAP-144-SR Study Group. AB - The clinical efficacy and safety of 3.75 or 7.5 mg leuprorelin acetate depot given subcutaneously once every 4 weeks was evaluated in a collaborative study of 81 patients with untreated prostatic cancer. Efficacy of treatment was assessed using criteria based on a meeting of the Prostatic Cancer Study Group funded by the Japanese Ministry of Health and Welfare and using National Prostatic Cancer Project criteria. Japanese criteria enabled evaluation of individual parameters, unlike the National Prostatic Cancer Project system which classified a patient as unevaluable if one evaluation parameter was unavailable. Leuprorelin acetate depot suppressed serum luteinizing hormone, follicle stimulating hormone and testosterone concentrations. Objective response rates of the prostate, bone metastases, serum prostatic acid phosphatase and soft tissue metastases, and subjective dysuria and pain responses were comparable to those found with conventional hormone therapy. Leuprorelin acetate depot was well tolerated, with no significant differences in response to the two doses. PMID- 2108890 TI - The effect of bovine activin and follicle-stimulating hormone (FSH) suppressing protein/follistatin on FSH-induced differentiation of rat granulosa cells in vitro. AB - The time- and dose-dependent effects of bovine activin A and bovine follicle stimulating hormone (FSH) suppressing protein (FSP) or follistatin on basal and FSH-induced steroidogenesis and inhibin production were studied in granulosa cells from immature, diethylstilbestrol (DES)-treated rats. In the presence of rat FSH (20 ng/ml) which stimulates aromatase activity and the production of progesterone and inhibin, activin (0.3-100 ng/ml) augmented all three parameters, whereas FSP (0.3-100 ng/ml) enhanced progesterone production and attenuated the other two parameters. In the absence of FSH, the basal parameters were unaffected by treatment with either activin or FSP alone, except for a statistically significant increase in basal inhibin in the presence of activin alone (P less than 0.05, at doses of 30 and 100 ng/ml). Neither activin nor FSP influenced the timing of the maxima of FSH-induced activities over 5 days. These findings suggest that activin and FSP, both present in follicular fluid, may play an important role in the local regulation of granulosa cell differentiation. PMID- 2108891 TI - [Non-A non-B, type C hepatitis]. PMID- 2108892 TI - Influence of hyperalimentation on rat hepatic microsomal fluidity and function. AB - Total parenteral nutrition with an amino acid-glucose solution has previously been shown to decrease rat hepatic drug metabolism compared with drug metabolic activity observed in rats receiving the same solution enterally and chow-fed animals. Because changes in membrane fluidity and lipid composition are reported to influence activity of a number of liver enzymes, effects of parenteral and enteral nutrition on hepatic microsomal membrane fluidity and lipid composition were assessed and compared with hepatic mixed-function oxidase activity. Both parenteral and enteral hyperalimentation produced a significant decrease in microsomal membrane fluidity (fluorescence anisotropy = 0.155 +/- 0.003 in both experimental groups versus 0.129 +/- 0.003 for microsomes from chow-fed animals). However, meperidine demethylase activity was significantly decreased compared with chow-fed experiments only in hepatic microsomes from parenterally hyperalimented animals, whereas ethoxyresorufin deethylase activity was significantly reduced only in the enteral-nutrition group. Inclusion of lipid in the parenterally administered hyperalimentation solution normalized microsomal membrane fluidity and lipid profile to those of chow-fed animals but did not increase hepatic meperidine demethylation. Both parenteral and enteral nutrition produce significant changes in physical state and lipid composition of rat hepatic microsomal membranes, but these changes are not responsible for the altered hepatic drug metabolism observed during hyperalimentation. PMID- 2108893 TI - Interferon treatment of chronic non-A, non-B (HCV) hepatitis: the saga continues. PMID- 2108894 TI - Localization of an origin of replication in Corynebacterium diphtheriae broad host range plasmid pNG2 that also functions in Escherichia coli. AB - Subcloning and protoplast transformation studies identified a 2.6 kb fragment of Corynebacterium diphtheriae plasmid pNG2 which contains an origin of replication (oriR). Molecular combination of the 2.6 kb oriR cartridge with Escherichia coli plasmid pUC18CmR enabled the E. coli cloning vector to replicate within several species of Corynebacterium host cells. A 2.6 kb plasmid formed from the oriR cartridge alone is capable of replicating in E. coli. This suggests that a single origin could be used in vectors shuttling between Corynebacterium spp. and E. coli. PMID- 2108895 TI - Organization and nucleotide sequence of the genes for ribosomal protein S2 and elongation factor Ts in Spirulina platensis. AB - A 6.5 kb region from the genome of the cyanobacterium Spirulina platensis was cloned using as a probe the Escherichia coli gene for ribosomal protein S2. Sequence analysis revealed, in this region, the presence of the gene for ribosomal protein S2 and part of the gene for the elongation factor Ts (EF-Ts). The arrangement rpsB-spacer-tsf resembles that reported for E. coli. The deduced amino acid sequences of the platensis S2 and EF-Ts show significant homology with the E. coli counterparts. PMID- 2108896 TI - Differences between the mechanisms of action of heat-stable and heat-labile enterotoxins of Escherichia coli. AB - The mucosal-to-serosal and serosal-to-mucosal fluxes of Na+ and Cl- were measured in control mice and mice treated with heat-stable (ST) and heat-labile (LT) enterotoxins in the presence or absence of: Ca2(+)-ionophore A23187, an activator of Ca2(+)-calmodulin; or phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C(PKC); or 1-(5-isoquinolinyl sulphonyl)-2-methyl piperazine (H 7), an inhibitor of PKC. There was net secretion of Na+ and CL- in both experimental groups in contrast to net absorption in the control group. The addition of ionophore or PMA or ionophore + PMA resulted in net secretion of Na+ and Cl- in the control group and the effect of ionophore and pMA was found to be additive. The addition of ionophore did not cause any change in electrolyte fluxes in the ST toxin treated group, however, it increased the net secretion of Na+ and Cl- in the LT toxin treated group. PMA increased the net secretion of Na+ and Cl- in the St toxin treated group, however, it did not cause any change in Na+ and Cl- fluxes in the LT toxin treated group. H-7 did not reverse the effect of ST toxin, however, it reversed the effect of LT toxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108897 TI - Interspecies electro-transformation in Corynebacteria. AB - Plasmid DNA was efficiently electro-transformed into intact cells of nine Corynebacteria strains belonging to Brevibacterium lactofermentum, Brevibacterium flavum, Corynebacterium glutamicum and Corynebacterium melassecola. Relationships were explored between transformation efficiency and parameters such as electric field strength and pulse length, DNA concentration, physiological state and concentration of the cells. In optimal conditions, more than 10(7) transformants per microgram of DNA could be obtained. Electro-transformation with plasmid DNA isolated from different sources indicates that DNA modification may play a role in transformation efficiency. PMID- 2108898 TI - Uptake of L-[14C]-alanine by glutaraldehyde-treated and untreated spores of Bacillus subtilis. AB - The effect of glutaraldehyde on the uptake of L-alanine, and subsequent germination, in spores of Bacillus subtilis NCTC 8236 was examined. Germination was induced by single amino acids, D-glucose and phosphate buffer at 37 degrees C. L-alanine was the best germinant of all amino acids tested. Pretreatment of spores with low concentrations of acid and alkaline glutaraldehyde inhibited subsequent germination, complete inhibition being observed at concentrations of 0.1% (w/v). This concentration also prevented the loss of heat resistance of spores placed in germination medium and exposed to 75 degrees C. Radioactive studies indicated that maximum uptake of L-alanine occurred after ca 30 min at 37 degrees C. Only 1.2% of available L-alanine was taken up during germination. Pretreatment of spores with glutaraldehyde did not interfere with L-alanine uptake at aldehyde concentrations up to 0.5% (w/v). However, this was significantly reduced at a glutaraldehyde concentration of 1.0% (w/v). Minimal differences were observed between acid and alkaline forms of the aldehyde. The results are discussed in terms of the mode of action of glutaraldehyde. PMID- 2108899 TI - DNA sequence homology between attB-related sites of Corynebacterium diphtheriae, Corynebacterium ulcerans, Corynebacterium glutamicum, and the attP site of gamma corynephage. AB - Chromosomal restriction fragments of Corynebacterium ulcerans and C. diphtheriae, containing an integration site for corynephages of the beta family, show homology on Southern blots. Homologous DNA in also found in the soil isolate C. glutamicum, although this strain is not susceptible to beta-corynephages. Three of these DNA fragments, one for each bacterial strain, and a fragment of gamma corynephage DNA previously shown to contain the phage integration site, were cloned and sequenced. Alignment of the 3 bacterial sequences shows a very high degree of homology in a stretch of ca 120 nucleotides, whereas the rest of the sequences is generally non-homologous. Within this common bacterial portion, a segment of ca. 96 nucleotides (core sequence) is also highly homologous to the phage sequence. The first half (ca. 50 bp) of the core sequence is identical in all aligned sequences whereas the second half, which is largely occupied by a stem-and-loop structure, contains point mutations peculiar to each clone. The described sequences are likely to be involved in phage integration/excision processes. PMID- 2108900 TI - A surface polysaccharide forms when gonococci are converted to serum resistance by cytidine 5'-monophospho-N-acetyl neuraminic acid. AB - A serum-susceptible, guinea-pig chamber-passaged, laboratory strain (BS4 (agar)) of Neisseria gonorrhoeae was converted to serum resistance by incubation with cytidine 5-monophospho-N-acetyl neuraminic acid (CMP-NANA) and examined by electron microscopy after staining with ruthenium-red. In contrast to serum susceptible gonococci incubated without CMP-NANA, the majority (60-70%) of the serum resistant organisms showed a surface accumulation of polysaccharide. This surface polysaccharide was enhanced on all the resistant gonococci after incubation with fresh human serum. Control susceptible gonococci were devoid of the polysaccharide after incubation with heated human serum. Identical results were obtained with a fresh gonococcal isolate which had lost serum resistance on subculture but which, in common with 3 other isolates, was restored to serum resistance by incubation with CMP-NANA. PMID- 2108901 TI - A heat-labile enterotoxin (LT) purified from chicken enterotoxigenic Escherichia coli is identical to porcine LT. AB - We have previously reported that the heat-labile enterotoxin (LTc) isolated from a chicken enterotoxigenic Escherichia coli (ETEC) was identical to LTh produced by human ETEC (Tsuji et al. (1988) FEMS Microbiol Lett. 52, 79-84). In this study, we purified an LTc-like toxin (LTc') from another strain isolated from a chicken that developed diarrhea at a different place and time to the previously reported chicken. Its molecular weight and antigenicity were compared with those of purified LTs from porcine and human ETEC (LTp and LTh). The A subunit of LTc' was identical to those of the purified LTs in mobility on SDS-polyacrylamide gel electrophoresis. The Ouchterlony test demonstrated that LTc' was antigenically identical to LTp. The isoelectric point and amino acid composition of LTc' were also identical to those of LTp. These data suggest that chicken ETEC can be grouped with both the porcine and human types on the basis of the LTs produced. PMID- 2108902 TI - The foundations of genetic fine structure: a retrospective from memory. PMID- 2108903 TI - Developmental expression of the glucose dehydrogenase gene in Drosophila melanogaster. AB - The Gld gene of Drosophila melanogaster is transiently expressed during every stage of development. The temporal pattern of Gld expression is highly correlated with that of ecdysteroids. Exogeneous treatment of third instar larvae with 20 hydroxyecdysone induces the accumulation of Gld mRNA in the hypoderm and anterior spiracular gland cells. During metamorphosis Gld is expressed in a variety of tissues derived from the ectoderm. In the developing reproductive tract, Gld mRNA accumulates in the female spermathecae and oviduct and in the male ejaculatory duct and ejaculatory bulb. These four organs are derived from closely related cell lineages in the genital imaginal disc. Since the expression of Gld is not required for the development of these reproductive structures, this spatial pattern of expression is most likely a fortuitous consequence of a shared regulatory factor in this cell lineage. At the adult stage a high level of the Gld mRNA is only observed in the male ejaculatory duct. PMID- 2108904 TI - Genetic analysis of the adenosine3 (Gart) region of the second chromosome of Drosophila melanogaster. AB - The Gart gene of Drosophila melanogaster is known, from molecular biological evidence, to encode a polypeptide that serves three enzymatic functions in purine biosynthesis. It is located in polytene chromosome region 27D. One mutation in the gene (ade3(1)) has been described previously. We report here forty new ethyl methanesulfonate-induced mutations selected aga!nst a synthetic deficiency of the region from 27C2-9 to ++28B3-4. The mutations were characterized cytogenetically and by complementation analysis. The analysis apparently identifies 12 simple complementation groups. In addition, two segments of the chromosome exhibit complex complementation behavior. The first, the 28A region, gave three recessive lethals and also contains three known visible mutants, spade (spd), Sternopleural (Sp) and wingless (wg); a complex pattern of genetic interaction in the region incorporates both the new and the previously known mutants. The second region is at 27D, where seven extreme semilethal mutations give a complex complementation pattern that also incorporates ade3(1). Since ade3(1) is defective in one of the enzymatic functions encoded in the Gart gene, we assume the other seven also affect the gene. The complexity of the complementation pattern presumably reflects the functional complexity of the gene product. The phenotypic effects of the mutants at 27D are very similar to those described for ade2 mutations, which also interrupt purine biosynthesis. PMID- 2108905 TI - A genetic basis for the inviability of hybrids between sibling species of Drosophila. AB - A mutation of Drosophila melanogaster whose only known effect is the rescue of otherwise lethal interspecific hybrids has been characterized. This mutation, Hmr, maps to 1-31.84 (9D1-9E4). Hmr may be the consequence of a P element insertion. It rescues hybrid males from the cross of D. melanogaster females to males of its three sibling species, D. simulans, D. mauritiana and D. sechellia. This rescue is recessive, since hybrid males that carry both Hmr and a duplication expected to be Hmr+ are not rescued. Hmr also rescues the otherwise inviable female hybrids from the cross of compound-X D. melanogaster females to males of its sibling species. This rescue is also recessive, since a compound-X heterozygous for Hmr does not rescue. Another mutation, discovered on the In(1)AB chromosome of D. melanogaster, is also found to rescue normally inviable species hybrids: unlike Hmr, however, In(1)AB rescues hybrid females from the cross of In(1)AB/Y males to sibling females, as well as hybrid males from the cross of In(1)AB females to sibling males. These data are interpreted on the basis of a model for the genetic basis of hybrid inviability of complementary genes. PMID- 2108906 TI - An inducible expression vector for both fission and budding yeast. AB - We have developed a vector system for inducible gene expression in both fission yeast (Schizosaccharomyces pombe) and budding yeast (Saccharomyces cerevisiae). The autonomously replicating expression vector contains multiple glucocorticoid response elements, rendering a linked promoter inducible 20-70-fold by glucocorticoid hormones in the presence of the mammalian glucocorticoid receptor. A polylinker with several unique cloning sites allows insertion of cDNAs of interest. Glucocorticoids are gratuitous signalling molecules in yeast, exerting little or no effect on the expression of genes other than those fused to the regulated promoter. PMID- 2108907 TI - Of mice and yeast: versatile vectors which permit gene expression in both budding yeast and higher eukaryotic cells. AB - Gene expression in heterologous species is a powerful tool for the cloning and characterization of genes. Here, we present a family of expression shuttle vectors which work in the budding yeast, Saccharomyces cerevisiae, and also in mammalian cells. The quantity of product expressed by the gene under study can be modulated in yeast by virtue of the control over plasmid copy number and culture conditions. PMID- 2108908 TI - Effect of pravastatin on biliary lipid composition and bile acid synthesis in familial hypercholesterolaemia. AB - Nine patients with heterozygous familial hypercholesterolaemia were treated for eight weeks with either 40 mg pravastatin or placebo under double blind conditions. Six patients received pravastatin, a competitive inhibitor of 3 hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Treatment with pravastatin resulted in a significant decrease in plasma cholesterol caused by a decrease in low density lipoprotein cholesterol (LDL-c) of 30% (p less than 0.005). We determined the effect of this medication on the lithogenicity of bile. Cholesterol saturation index of fasting gall bladder bile decreased with 23% (p less than 0.01) from 1.06 to 0.75 during treatment with pravastatin. A reduction of 24% (p less than 0.01) in molar percentage of biliary cholesterol was seen. After treatment the total bile acid excretion in faeces and the molar percentage of biliary bile acids were not significantly changed, suggesting that pravastatin does not influence bile acid biosynthesis to a significant extent. These findings indicate that treatment with pravastatin can decrease the incidence and complications of cholesterol gall stones. PMID- 2108909 TI - Preliminary results of concurrent radiotherapy and chemotherapy in advanced cervical carcinoma: a phase I-II prospective intergroup NCOG-RTOG Study. AB - Thirty-eight patients with advanced carcinoma of the cervix were prospectively treated with a concurrent combination of radiotherapy (RT) and chemotherapy (CT) using the drugs 5-fluorouracil (5FU), mitomycin C and cis-platinum as part of a Northern California Oncology Group (NCOG) and Radiation Therapy Oncology Group (RTOG) intergroup study. RT consisted of 36.00 Gy to the pelvis in 4 weeks followed by a 9.00-Gy parametrial boost. This was followed by two intracavitary applications for a total of 4000 mg hr of radium equivalent when possible. 5FU (1000 mg/m2/24 hr for 96 hr by iv infusion) and mitomycin C (10 mg/m2/iv bolus) were given during the second week of external RT. 5FU (dose as above) and cis platinum (75 mg/m2/iv over 6 hr) were given during the first intracavitary application. Of 36 patients evaluable for toxicity, 11% had grade 3 nonhematological toxicity and 11% had reversible grade 4 hematological toxicity. There were no toxic deaths. A complete response rate of 62.5% was obtained overall (median survival not reached). This study suggests that this particular combination of RT and CT in advanced cervical carcinoma is effective and well tolerated. PMID- 2108910 TI - Interferon gamma treatment for cervical intraepithelial neoplasia. AB - Eight patients with cervical intraepithelial neoplasia (CIN) were administered perilesional injections of human recombinant interferon gamma (IFN-gamma), and the response was evaluated by colposcopy and exfoliative cytology and then by histopathology. In all patients, colposcopic and cytologic findings improved after two to four injections of IFN-gamma and the cytologic findings reverted to normal in five of these eight patients. All five were free of dysplastic lesions. The other three patients with positive cytology and positive colposcopy after completion of IFN-gamma treatment underwent hysterectomy or laser conization, and histopathologic examination revealed residual dysplastic lesions. On the other hand, a control study revealed that only one of eight patients showed spontaneous regression during the 3-month observation period. During the course of these treatments, keratinizing cells were often present in the cervical smears and isolated cell keratinization was often evident in the residual dysplastic lesions of the surgical specimens. These observations suggest that IFN-gamma treatment is an effective therapeutic method for CIN lesions and that IFN-gamma has the potential to differentiate nonkeratinizing squamous cells into keratinizing cells. PMID- 2108911 TI - Prevention of infection in acute leukemia. AB - In a randomized study comparing cotrimoxazole plus colistin with ciprofloxacin, each in combination with nonabsorbable antimycotics, the incidence of major infections in terms of septicemias and pneumonias as well as of minor infections and episodes of unexplained fever (FUO) was higher in patients treated with ciprofloxacin. In cases of microbiologically documented infections, gram-positive cocci dominated by far. In surveillance cultures of oral washings and of feces, gram-negative enterobacteria were only rarely detected; however, large numbers of cultures were positive for Acinetobacter species. There were four cases of documented Pneumocystis carinii pneumonia in patients not receiving cotrimoxazole. The incidence of documented mycotic infections as well as the detection of fungi in surveillance cultures was similar in both treatment groups. A decrease in the number of adverse events, especially of allergic reactions, could not be achieved by the administration of ciprofloxacin. In conclusion, cotrimoxazole plus colistin in combination with nonabsorbable antimycotics remains the standard regimen for prevention of infection in patients with acute leukemia undergoing aggressive remission induction therapy. A detailed analysis of study II will be prepared for publication. PMID- 2108912 TI - 1-Deamino-8-D-arginine vasopressin in the treatment of non-haemophilic patients with acquired factor VIII inhibitor. AB - 1-Deamino-8-D-arginine vasopressin (DDAVP) was administered to 3 patients with spontaneous factor VIII inhibitors. In 2 patients with baseline factor VIII levels above 1%, a marked increase of factor VIII activity after DDAVP infusion could be observed. No rise of factor VIII activity after DDAVP was seen in the 3rd patient with a baseline factor VIII level of less than 1%. Daily infusion of DDAVP resulted in a reduction of the efficacy, but the full effect could be retained when DDAVP was given at 48-hour intervals. The effect of DDAVP infusion on factor VIII levels in the 2 responding patients was superior to the treatment with 30 U/kg factor VIII concentrate and approximately equivalent to infusion of 45 U/kg factor VIII concentrate. DDAVP may be a useful and less expensive treatment for patients with acquired factor VIII inhibitors and a baseline factor VIII level of more than 1%. PMID- 2108913 TI - Reduced levels of tissue plasminogen activator and plasminogen activator inhibitor in plasma of patients with familial amyloidotic polyneuropathy. AB - Tissue plasminogen activator (tPA) antigen levels and plasminogen activator inhibitor (PAI) activity were measured in the plasma from 23 patients with familial amyloidotic polyneuropathy. Both tPA levels and PAI activity were reduced to about half normal, even when the effects of patient age and body mass index were taken into account. There were higher mean tPA levels and PAI activity in patients with mild disability than in those with moderate or severe disability, but these differences were not statistically significant. There were normal tPA levels after venous occlusion of the upper arm, indicating a normal capacity of vascular endothelium to release tPA. This is the first reported disorder with reduced rather than increased basal tPA and PAI levels. The pathogenetic and clinical significances of these disturbances so far remain obscure. PMID- 2108914 TI - Food-sharing in cotton-top tamarins (Saguinus oedipus). AB - Food-sharing behaviour was observed in 9 captive families of cotton-top tamarins (range 4-14 individuals per group), during meals of fresh fruit. Food was transferred to infants by their parents and older sibs in response to begging, and was also offered to them without prior solicitation. Older, mature, reproductively suppressed individuals shared more than young immature monkeys. Infants in larger families received more food than those in smaller ones, though individuals in smaller families shared more. Transfer to infants increased to a maximum at 12 weeks of age and then declined gradually. At one year of age they no longer received food from others. Food sharing by older siblings is a form of helping behaviour which may increase their inclusive fitness, and benefit parents, both directly, by reducing the costs they incur in rearing young, and indirectly, by increasing the amount of food available to infants. PMID- 2108915 TI - Medial hypothalamic lesions and sexual receptivity in the female common marmoset (Callithrix jacchus). AB - Medial hypothalamic lesions cause major deficits in sexual receptivity in a variety of mammalian species. Effects of such lesions upon sexual receptivity in female primates have not been investigated. Two experiments are described in which thermal lesions were made in the hypothalamus in 11 ovariectomized or ovariectomized/adrenalectomized, oestradiol-treated common marmosets. Proceptivity (sexual initiating behaviour) was reduced or abolished by lesions in the dorsomedial or ventromedial hypothalamus. Sexual receptivity was unaffected except in 3 females in which damage to the ventromedial area was associated with a 25-42% increase in terminations of males' mounts. However, this effect was reversed by treating females with oestradiol. Therefore, medial hypothalamic lesions have pronounced effects upon proceptivity in the marmoset, whereas effects upon receptivity are much less pronounced or absent. These results are discussed in relation to the evolution of the hormonal control of receptivity in anthropoid primates as compared to other mammals. PMID- 2108916 TI - [Various questions concerning the treatment of renal cell carcinoma]. PMID- 2108917 TI - Paying for public mental health care: crucial questions. PMID- 2108918 TI - Listen to child health experts, not economists. PMID- 2108919 TI - A pluralistic solution to rising health costs. PMID- 2108920 TI - Increased growth hormone responses to growth hormone releasing hormone and thyrotropin releasing hormone in patients with metastatic testicular cancer. AB - In 16 patients with metastatic testicular cancer and 10 age matched male control subjects growth hormone (GH) responses to growth hormone releasing hormone (GHRH; 1 microgram/kg body weight iv.) and thyrotropin releasing hormone (TRH; 200 micrograms iv.) were measured. Basal GH levels and GH levels following stimulation with GHRH or TRH were significantly increased in cancer patients compared to control subjects. 9 patients with testicular cancer were studied both in the stage of metastatic disease and after they had reached a complete remission. In complete remission GH responses to GHRH tended to decrease but the differences did not reach statistical significance. Our data suggest an alteration of hypothalamic and/or pituitary regulation of GH secretion in patients with metastatic testicular cancer. PMID- 2108921 TI - A case of primary osseous malignant immunoblastic B-cell lymphoma with intracytoplasmic mu lambda immunoglobulin inclusions. AB - Primary malignant lymphoma of bone, so-called Parker-Jackson reticulosarcoma, is a rare form of extranodal lymphoma with a relatively good prognosis. It often corresponds to B-cell lymphoma of high-grade malignancy. We report a case of mu lambda immunoblastic lymphoma showing two distinctive features: an abundant reactive T-lymphocytic population and unusual intra-cytoplasmic inclusions. These inclusions were PAS positive and consisted of monotypic mu lambda immunoglobulin localized in peculiar aggregates of rough endoplasmic reticulum. Their morphological appearances resembled the well-documented inclusions described in some varieties of non-Hodgkin's lymphoma. PMID- 2108922 TI - Localization of the human HF.10 finger gene on a chromosome region (3p21-22) frequently deleted in human cancers. AB - The finger motif is a tandemly repeated DNA-binding domain recently identified in the primary structure of several eukaryotic transcriptional regulatory proteins. It has been proposed that some members of the finger-gene family are implicated in both normal cell proliferation and differentiation. We isolated several human finger genes by means of hybridization with a finger motif-containing DNA probe. One of these finger genes, HF.10, is expressed at low levels in a variety of human tissues and is down-regulated during the in vitro terminal differentiation of human leukemic myeloid cell lines. By in situ hybridization experiments and analysis of interspecific somatic cell hybrids we mapped the HF.10 gene to 3p21 22, a chromosome region frequently involved in karyotypic rearrangements associated with lung and renal cancer. PMID- 2108923 TI - Telomere association of chromosomes induced by aphidicolin in a normal individual. AB - Telomere association of chromosomes of a phenotypically and mentally normal individual was detected in 11.7% of metaphases cultured in RPMI-1640 with aphidicolin. No preferential involvement of any chromosome pair was detected. In two other individuals the frequency of telomere associations was much lower (1.9% and 0.7% respectively) under the same culture conditions. In the first individual the high number of telomere associations in cultures with aphidicolin along with the presence of telomere association (2.4%) in cultures with F.10 medium alone could reflect a constitutional telomere anomaly that is more often expressed in the presence of aphidicolin. PMID- 2108924 TI - Apolipoprotein A1 Baltimore (Arg10----Leu), a new ApoA1 variant. AB - A new apolipoprotein A1 (APOA1) gene variant has been identified in a family ascertained through a proband undergoing coronary angiography. The variant, ApoA1 Baltimore, was due to a mutation at codon 34 of the third exon of the APOA1 gene (CGA to CTA) that resulted in an arginine-to-leucine substitution at the tenth amino acid of the mature ApoA1 and a change in charge of -1. The mutation abolishes a TaqI restriction site and it is easily detectable after polymerase chain reaction amplification of genomic DNA. The proband was heterozygous for the mutation. Eight other members of the pedigree had the same ApoA1 variant. Cosegregation of the variant with hypoalphalipoproteinemia could not be demonstrated and the association of this mutation with hypoalphalipoproteinemia was confined to three affected members of the nuclear family. No effect of the mutant on any lipoprotein phenotype could be established. PMID- 2108925 TI - Talc granulomatosis in the rat. Involvement of bone in the acute-phase response. AB - We investigated the dynamics of the acute-phase response (APR) and osteoblast trabecular surface in rats with subcutaneous inflammation provoked by magnesium silicate (talc). The first visible indicator of the APR was a rapid and profound hypozincemia, paralleled by a decrease in metaphyseal trabecular surfaces covered with osteoblasts in long bones. Both the intensity of serum APR and the decrease in osteoblast trabecular surface were directly proportional to the number of granulomas. Alterations in bone metabolism were specific for the inflammation, whereas mild hypozincemia and decrease in mononuclear and increase in polymorphonuclear peripheral white blood cell fractions developed in animals pair fed with rats bearing two or four granulomas. Rats with talc granulomatosis had high serum ACTH and corticosterone levels, but neither adrenalectomy nor high doses of hydrocortisone could revert bone alterations in talc-injected animals. Glucocorticoids were necessary for the development of hypozincemia and hypercupremia seen in talc granulomatosis, as well as for normal bone metabolism. Inhibition of prostaglandin synthesis had no effect on bone alterations and serum APR in rats bearing talc-induced granulomas. We conclude that the decrease in bone formation constitutes an important aspect of the host acute-phase response in a rat model of talc granulomatosis. PMID- 2108926 TI - Secretion of toxin A from Pseudomonas aeruginosa PAO1, PAK, and PA103 by Escherichia coli. AB - The exotoxin A gene (toxA) from Pseudomonas aeruginosa PAO1 was expressed from the lac promoter in Escherichia coli, and the localization of the toxin A protein was determined. Throughout the growth cycle, the ADP-ribosyltransferase activity of toxin A was gradually reduced in the periplasm of E. coli, with no apparent degradation of the toxin A protein. This suggests the presence of an E. coli periplasmic factor that interferes with the ADP-ribosyltransferase activity in toxin A. Such an inactivating factor was found in the periplasmic extract from control E. coli cells. The processing of toxin A in E. coli was examined by pulse chase immunoprecipitation experiments. Mature toxin was detected in both the periplasm and cytoplasm, whereas the membranes contained both mature and precursor forms. Toxin A precursor appears to be processed in both the cytoplasm and the periplasm of E. coli. Toxin A proteins from P. aeruginosa PAO1, PA103, and PAK were compared for their secretion in E. coli. Despite the differences in the amino acid sequences of their leader peptides, toxin A proteins from strains PAO1, PA103, and PAK were processed and secreted to the periplasm of E. coli. PMID- 2108928 TI - Difference in the induction of macrophage interleukin-1 production between viable and killed cells of Listeria monocytogenes. AB - T-cell-mediated immunity to Listeria monocytogenes in mice, as determined by delayed-type hypersensitivity and acquired resistance, was induced by immunization with viable bacteria but not with killed bacteria, even when killed cells were injected in a high dose or repeatedly. T cells obtained from mice immunized with viable L. monocytogenes were readily stimulated with killed bacterial antigens, resulting in T-cell proliferation in vitro and expression of a delayed footpad reaction in vivo. After immunization with killed-bacterial vaccine, T-cell responsiveness to interleukin 2 (IL-2) never developed but a lower level of responsiveness to IL-1 appeared later than with T cells from mice immunized with viable bacteria. When IL-1 production by macrophages was examined in vitro, viable L. monocytogenes stimulated a high level of IL-1 release while killed bacteria did not. Avirulent strains which were ineffective in the induction of T-cell mediated immunity were incapable of inducing IL-1 production as well. The impaired ability of killed bacteria to stimulate IL-1 production was confirmed by the level of IL-1 mRNA expression. These results suggested that the ineffectiveness of killed L. monocytogenes vaccine is not due to loss or lack of antigenic epitopes but may be ascribed to insufficient induction of IL-1 production in the initial stage of the immune response in vivo. PMID- 2108929 TI - Characterization of Pseudomonas aeruginosa adherence to mouse corneas in organ culture. AB - The present study was designed to obtain further information on the nature of the corneal macromolecule(s) to which Pseudomonas aeruginosa adheres and how adherence might be prevented. Scarified adult mouse corneas in organ culture were treated with trypsin or lipase to determine whether the receptor molecule(s) was protein or lipid in nature. Trypsin (20 micrograms/ml) treatment of the cornea for 5 min had no significant effect on bacterial adherence, and longer periods of enzyme exposure resulted in extensive surface cell lysis. In contrast, lipase treatment (50,000 U/ml) for 1 h caused little visible cell lysis and significantly reduced bacterial adherence. To test further the lipid nature of the receptor, a highly purified monosialoganglioside (GM1) preparation (500 micrograms/ml) was used to preincubate (1 h) the cornea prior to bacterial application, and this also inhibited bacterial adherence. Similar corneal treatment with gangliotetraosylceramide (asialo GM1) (500 micrograms/ml) had little effect on ocular bacterial binding. Premixing of the bacterial inoculum with GM1 prior to corneal application had no significant effect on inhibiting bacterial binding, but similarly premixing the bacterial inoculum with asialo GM1 transiently decreased adherence. Lastly, premixing of the bacterial inoculum or preincubation of corneas with fibronectin (500 micrograms/ml for 1 h) both decreased bacterial adherence. These findings provide evidence that the receptor adhesin interactions of P. aeruginosa at the ocular surface in organ culture are complex, involve a glycolipid moiety, and may be blocked by a ganglioside containing at least one sialosyl residue or by fibronectin, which may bind to membrane-associated gangliosides. PMID- 2108930 TI - Molecular cloning and sequence analysis of the Sta58 major antigen gene of Rickettsia tsutsugamushi: sequence homology and antigenic comparison of Sta58 to the 60-kilodalton family of stress proteins. AB - The scrub typhus 58-kilodalton (kDa) antigen (Sta58) of Rickettsia tsutsugamushi is a major protein antigen often recognized by humans infected with scrub typhus rickettsiae. A 2.9-kilobase HindIII fragment containing a complete sta58 gene was cloned in Escherichia coli and found to express the entire Sta58 antigen and a smaller protein with an apparent molecular mass of 11 kDa (Stp11). DNA sequence analysis of the 2.9-kilobase HindIII fragment revealed two adjacent open reading frames encoding proteins of 11 (Stp11) and 60 (Sta58) kDa. Comparisons of deduced amino acid sequences disclosed a high degree of homology between the R. tsutsugamushi proteins Stp11 and Sta58 and the E. coli proteins GroES and GroEL, respectively, and the family of primordial heat shock proteins designated Hsp10 Hsp60. Although the sequence homology between the Sta58 antigen and the Hsp60 protein family is striking, the Sta58 protein appeared to be antigenically distinct among a sample of other bacterial Hsp60 homologs, including the typhus group of rickettsiae. The antigenic uniqueness of the Sta58 antigen indicates that this protein may be a potentially protective antigen and a useful diagnostic reagent for scrub typhus fever. PMID- 2108931 TI - Low pH-induced changes in Pseudomonas exotoxin and its domains: increased binding of Triton X-114. AB - Pseudomonas exotoxin (PE), which is composed of three structural domains, is a 66 kilodalton protein secreted by P. aeruginosa that is cytotoxic for mammalian cells. After binding to cell surface receptors and internalization into low-pH endocytic vesicles, PE or an active fragment kills mammalian cells by translocating across an intracellular membrane to the cytoplasm and shutting down protein synthesis. To investigate possible conformational changes associated with the translocation process, full-length PE or recombinant proteins containing the PE cell recognition domain, translocation domain, enzymatic domain, or translocation plus enzymatic domains were incubated with Triton X-114 at pH values ranging from 3.0 to 7.0. The truncated forms used were intact domains that had been expressed in Escherichia coli and subsequently purified. Previous studies (K. Sandvig and J. O. Moskaug, Biochem. J. 245:899-901, 1987) had shown that full-length PE bound more Triton X-114 at a low pH than at a physiologic pH. Therefore, we investigated whether this increased binding was due to a global change in PE or a change within a particular domain. Results showed that all the truncated toxin proteins displayed a similar pH-dependent entry into the detergent phase as native PE, with a transition point of 4.2 for PE and 4.4 to 4.5 for the truncated toxins. The isoelectric points of the recombinant proteins were measured and indicate that, at a low pH (5.0), the cell recognition domain bears a net positive charge, the translocation domain bears a net negative charge, and the enzymatic domain bears no charge. The results suggest that upon acidification in the endosome, PE becomes globally hydrophobic and is converted into a translocation-competent form. PMID- 2108932 TI - Identification and partial characterization of Trypanosoma cruzi antigens recognized by T cells and immune sera from patients with Chagas' disease. AB - Trypanosoma cruzi antigenic specificities involved in human T-cell and antibody responses were compared in chronic chagasic patients affected with cardiomyopathy (C) or with the indeterminate form (I), the asymptomatic form of chronic Chagas' disease. T-cell Western blotting (immunoblotting) was performed to identify the most active antigens in epimastigote extracts (EPI-Ag). The patterns of peripheral blood mononuclear cell (PBMC) and T-cell proliferative responses induced by fractions blotted to nitrocellulose were heterogeneous, but the computation of their frequency distribution disclosed some important antigen specificities. Molecules ranging from 100 to 150 kilodaltons (kDa) were frequently stimulatory to PBMC from I patients (5 of 8 cases) and were less so when confronted with C patient (1 of 7 cases) lymphocytes. In contrast, both groups of patients actively responded to fractions ranging from 48 to 57 and 28 to 32 kilodaltons (kDa). The Western immunoblotting patterns of antibody reactivity displayed by 17 C and 15 I patients were also similar, yielding outstanding staining in the molecular mass ranges of 70 to 80 and 43 to 57 kDa. The latter antigen complex was recognized by 100% of the 32 chronic Chagas' disease serum specimens tested and closely corresponded to the migratory position recognized by T cells of most patients tested. The identification of the active molecules contained in the 43- to 57-kDa region was sought, with a focus on GP57/51, an antigen with well-established serodiagnostic properties. Immunoblotting analysis of EPI-Ag with a monoclonal antibody to GP57/51 confirmed its presence within the predicted molecular weight region. Highly purified GP51 was then used to demonstrate directly its capacity to promote specific PBMC proliferative responses in vitro. Data computed from a survey with 12 patients have shown a linear correlation (r = 0.93) between PBMC responses to EPI-Ag and to purified GP51, suggesting that the immune response to this particular glycoprotein may be an important component of human immune responses against T. cruzi. PMID- 2108934 TI - A novel technique for studies on the microvasculature of transplanted islets of Langerhans in vivo. AB - Transplantation of isolated islets of Langerhans in diabetic patients is frequently followed by an early loss of function due to acute rejection. Since the primary target of host-vs-graft reaction is the endothelium of the microvessels, it is of great importance to analyze the microcirculation of freely grafted pancreatic islets. For this purpose we present a new model, allowing for intravital microscopy of the microvasculature of transplanted islets of Langerhans. The islets are isolated from Syrian golden hamsters and DA-rats, respectively, by a modified collagenase digestion technique. Subsequently, the islets are transplanted into a hamster dorsal skinfold chamber. Using intravital fluorescence microscopy and video techniques, the microcirculation of the islet grafts can be observed repeatedly over a time period of up to four weeks. Quantitative analysis of the microhemodynamics, i.e. functional capillary density, capillary RBC-velocity and microvascular diameters, can be performed by means of a computer assisted image analysis system. In addition, the model allows for investigation of the flow behaviour of white blood cells and their interaction with the endothelium of the microvascular segments. For the first time a model is presented, enabling for in vivo analysis of the revascularization process and microcirculatory function of transplanted islets of Langerhans. Furthermore, the model allows to assess microvascular phenomena during host-vs graft reaction as well as effects of immunosuppressive regimens. PMID- 2108933 TI - Enhanced expression of the proto-oncogenes fos and raf in the rhabdomyosarcoma cell line BA-HAN-1C after differentiation induction with retinoic acid and N methylformamide. AB - BA-HAN-IC is a clonal rat rhabdomyosarcoma cell line consisting of proliferating mononuclear tumor cells, some of which spontaneously fuse to form terminally differentiated post-mitotic myotubes. Exposure of BA-HAN-IC cells to retinoic acid (RA) or N-methylformamide (NMF) resulted in a significant inhibition of proliferation (p less than 0.001) and in cellular differentiation, as evidenced by a significant increase in the creatine kinase (CK) activity (p less than 0.05) and the number of terminally differentiated post-mitotic myotubes (p less than 0.001). Furthermore, between 5% (NMF) and 30% (RA) of the mononuclear tumor cells exhibited ultrastructural features of rhabdomyogenic differentiation, not observed in their mononuclear counterparts under standard growth conditions. Although BA-HAN-IC cells responded to both inducers of differentiation, differences in time course and magnitude of both increase of differentiation and growth inhibition were observed. These effects of RA and NMF were preceded by a marked enhancement of c-raf expression which became evident 6 and 12 hr after exposure to RA and NMF, respectively, and which persisted throughout the observation period of 5 days. Furthermore, a transient expression of c-fos could be observed 15 and 30 min after exposure to RA. Our results suggest that c-raf expression might be implicated in the differentiation process of BA-HAN-IC tumor cells. PMID- 2108935 TI - Prospective payment experience with DRGs in headache patients. AB - The new Diagnostic Related Group (DRG) Prospective Hospital Payment System pays a set fee to hospitals depending on the patient's diagnosis. Care of certain patients covered by Neurology DRGs has proven to be unprofitable. The purpose of this project was to study hospital resource consumption for hospitalized patients with a principal or secondary diagnosis of headache. We studied various resource parameters for patients in the three neurology DRGs for headache (#24-seizure and headache, age greater than 69 and/or complicating condition; #25 and #26-seizure and headache age 18-69 without complicating condition, and age 0-17, respectively) by whether or not the patients had a diagnosis of headache. As demonstrated in Table 1, patients with headache had (on average) lower hospital resource utilization than patients in these same DRGs without a headache diagnosis. Headache patients had lesser total hospital costs, a lower severity of illness, and generated profits under DRGs compared to non-headache patients. We found that our headache patients were adequately reimbursed by the DRG hospital payment system and suggest that this could be a financially attractive population to hospitals. PMID- 2108936 TI - Ultraviolet radiation exposures in a mycobacteriology laboratory. PMID- 2108937 TI - The role of radiotherapy in the management of intracranial meningiomas: the Royal Marsden Hospital experience with 186 patients. AB - One hundred and eighty-six patients with intracranial meningiomas were treated at the Royal Marsden Hospital between 1963 and 1983 with megavoltage photon irradiation (60Co gamma rays and 6-8 Mv. X rays). Survival parameters were measured from the time of referral for radiotherapy. The 10-year actuarial cause specific survival was 67% for all cases and the actuarial disease-free survival was 61%. Both malignant and also "aggressive benign" histologies were associated with poor long-term survival. Benign angioblastic meningioma was associated with lower actuarial cause specific and disease-free survival compared with other benign histological sub-groups. Prognosis was related to the extent of initial surgical resection. Of those who underwent subtotal or partial tumor resection with post-operative radiotherapy the 10-year actuarial cause-specific survival was 77%, and in inoperable patients treated by radiotherapy alone it was 46%. Radiotherapy alone resulted in improvement of neurological performance (Karnofsky) in 12 out of the 32 (38%) patients with inoperable disease. The 10 year survival of patients referred for irradiation following "complete" surgical resection was only 34% owing to the high incidence of adverse histological sub types in this treatment sub-group. Based upon univariate analysis, performance status of less than 60 (Karnofsky) and also age greater than 50 years at the time of referral for radiotherapy were adverse prognostic factors. Multivariate analysis revealed that histological type, extent of surgical resection and performance status at the time of presentation for radiotherapy were independent prognostic variables. However age at the time of referral lost significance as an independent variable when analyzed using this method. Patients undergoing complete surgical resection for the typical benign non-aggressive meningioma do not require adjuvant irradiation. The results of this study support the role of radiotherapy for treatment of incompletely resected and inoperable meningioma of all 3 histological types (benign, "aggressive benign", malignant). PMID- 2108938 TI - Locally advanced breast cancer treated with neutron beams: long-term follow-up in 28 patients. AB - Between 1972 and 1978, 28 patients with locally advanced breast cancer were treated, 15 with neutron beams only and 13 with mixed neutron and photon beams. Half the patients had inflammatory cancer. For neutrons only, doses ranged between 13.35-25.34 nGy. In mixed-beam regimens, the prescribed total dose ranged between 62 and 76 Gy photon equivalent. Nine patients (32%) had a complete response without local recurrence for the duration of their survival ranging from 1 to 14+ years; 18 patients had a partial response (64%); and one patient had no change. Late toxicity was high: of 24 patients who received tangential breast irradiation, 5 (21%) had ulceration of the breast or chest wall, or both. In four patients, mastectomy and skin grafts were necessary for repair. In only one patient did the skin necrosis heal without corrective surgery. Twelve patients received axillary neutron irradiation, resulting in severe edema in four patients, and brachial plexopathy in six patients. Radiation-induced complications progressed steadily for the duration of the patients' survival after the neutron irradiation. The high complication rate encountered is attributed to high doses resulting from an under estimation of the relative biological effect of the neutron beam for late effects, and to the poor physical and geometrical characteristics of the neutron beam. PMID- 2108939 TI - The role of kilovoltage irradiation in the treatment of keloids. AB - This is a retrospective analysis of the results of kilovoltage irradiation given to prevent the regrowth of 203 keloids excised at the University of Iowa Hospitals and Clinics, Iowa City, Iowa, Lutheran Hospital in Moline, Illinois, and Mercy Hospital in Cedar Rapids, Iowa. We found that a minimum follow-up of 1 year is needed to evaluate the results of post-excisional kilovoltage x-ray therapy. A dose versus response effect was also observed. Although it is desirable to use the lowest possible dose of radiation that is likely to be effective, the likelihood of failure is too great to justify the routine use of doses of less than 900 cGy regardless of how they are fractionated or when they are given. It appears that the total dose of irradiation that is given to prevent the regrowth of an excised keloid is more important than when irradiation is started, the size of the largest fraction given, whether the irradiation is completed in 1 week or 3, or where the keloid has grown. When a small number of keloids were irradiated less than 1 year after they first appeared greater than or equal to 1500 cGy were sufficient to control 90% of them without re-excision. PMID- 2108940 TI - Persisting cyclical uterine bleeding in patients treated with radical radiation therapy and hormonal replacement for carcinoma of the cervix. AB - Radical radiation therapy used for carcinoma of the cervix will ablate ovarian function. Since January 1986, our policy has been to administer oral combination oestrogen-progesterone replacement hormonal therapy to all premenopausal patients undergoing radical radiation with or without synchronous chemotherapy, for invasive cervix cancer. Five out of 22 (23%) such patients unexpectedly experienced between one and four episodes of cyclical per vaginal bleeding after the completion of radiation therapy. Bleeding episodes occurred in the absence of persistent tumor or radiation reaction, and suggest persisting endometrial response to exogenous hormonal stimulation. Uterine activity was temporarily retained in these five patients despite a minimal endometrial surface dose of between 4800 and 6490 cGy. The limited number of cycles before bleeding spontaneously ceased may represent the slow death of endometrial cells subsequent to radiation or radiochemotherapy treatment, and has not previously been described. In view of the paucity of data on the radiosensitivity of normal endometrium, we have carefully examined these patients who appear to have retained endometrial sensitivity to hormonal stimuli after radical radiation chemotherapy for uterine cervix cancer. PMID- 2108941 TI - [Pregnancy and immunization]. PMID- 2108942 TI - Proposed distal margin for resection of rectal cancer. AB - To determine the adequate distal margin, particularly from the point of extent of lymph node metastasis, 2,333 lymph nodes from 44 patients with rectal carcinoma were evaluated, using a clearing method. The tumors were divided into two growth patterns; infiltrative and localized. Lymph node metastasis was histo pathologically examined with special attention focused on nodes on the distal side of the tumor. The intramural spread was also given attention. The proximal pararectal lymph nodes often contained malignant cells, whereas the distal ones were rarely involved, and if involved, they were present within 1 cm from the tumor. Pararectal lymph node metastasis and intramural spread were seen with a range of 1 cm and 0.5 cm, respectively, in the localized type and 1 cm and 2.1 cm, respectively in the infiltrative type. Based on these findings, the distal margin for surgical resection of rectal carcinoma is considered to be 2 cm for the localized type and 3 cm for the infiltrative type. PMID- 2108943 TI - Simulation of dynamic changes of human T-cell leukemia virus type I carriage rates. AB - The human T-cell leukemia virus type I (HTLV-I) is transmitted via breast milk, semen, or blood transfusion. The last route was not responsible for HTLV-I infection before the advent of modern medicine, nor will it be a major route in the future because anti HTLV-I antibody-positive blood is now screened out. Thus, the carriage rates in various areas of Japan have to be explained by the former two transmission methods. Based on the relationship between the two modes of transmission and carriage rates, several simulation experiments were performed. These experiments revealed that: (a) No population with a vertical transmission rate lower than 50% can be maintained as endemic for the virus. (b) Slight differences in horizontal transmission rates can cause a large change of the carriage rates. (c) A 1,000-fold carriage rate difference would become indistinguishable within a hundred generations if both modes of transmission were operating at nearly the same rate. (d) The probability of a formerly non-endemic population becoming endemic due to a single female carrier is not negligible. (e) Prevention of vertical transmission is much more effective in lessening the carriage rate within a short period of time than is prevention of horizontal transmission. A simulation for a real population is also presented. PMID- 2108944 TI - Point mutations of c-ras genes in human bladder cancer and kidney cancer. AB - Point mutations of c-ras genes at codons 12, 13 and 61 were analyzed in 26 cases of bladder cancer and 16 cases of kidney cancer. DNA prepared from either frozen tissues or 10% formalin-fixed, paraffin-embedded tissues were amplified by means of polymerase chain reaction methods, and mutations were analyzed by dot blot hybridization assays with oligonucleotide probes. In three cases of bladder cancer c-ras mutations were found, at codons 13 and 61 of c-Ha-ras and at codon 61 of c-Ki-ras, while no mutation was found in kidney cancer. No mutation was found in normal bladder epithelial tissues from the same patients. Our findings, taken together, may indicate relative scarcity of c-ras mutations in these types of human cancer. The results of dot blot hybridization assays and DNA sequencing showed a G-to-C transition of the first nucleotide at codon 13 c-Ha-ras. This is the first time that such a point mutation has been detected in human cancer tissues. PMID- 2108946 TI - Effects of growth factors and hormones on growth and morphological differentiation of human breast epithelial cells within collagen gel in serum free medium. AB - When human epithelial cells that had grown out from either carcinoma or histologically non-malignant breast tissues were seeded within type I collagen gels in serum-free medium, they successively grew and protruded many radial duct like extensions with lumina. Separate deletion of each of the supplements from the medium showed that growth as well as morphological differentiation of carcinoma-derived cells were prevented in the absence of epidermal growth factor (EGF) or hydrocortisone. Removal of insulin or ethanolamine plus phosphoethanolamine caused a significant inhibition of cell growth without interfering with the morphological differentiation. Contrary to the case with carcinoma-derived cells, both growth and morphological differentiation of epithelial cells derived from non-malignant breast tissues were prevented when EGF, hydrocortisone or insulin was absent. Removal of each of the other supplements (except for transferrin), including ethanolamine plus phosphoethanolamine, prolactin, or prostaglandin, caused a significant inhibition of cell growth with no apparent inhibition of morphological differentiation. The present results suggest that human epithelial cells derived from either carcinoma or histologically non-malignant breast tissues strongly depend on the presence of EGF and hydrocortisone and there is a decreased dependence on insulin in carcinoma-derived cells with respect to their growth and morphological differentiation during culture within collagen gels. PMID- 2108945 TI - Expression of epidermal growth factor, transforming growth factor-alpha and their receptor genes in human gastric carcinomas; implication for autocrine growth. AB - The expressions of mRNA for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and EGF receptor (EGFR) genes were examined in 7 human gastric carcinoma cell lines and 15 gastric carcinoma tissues and the corresponding normal mucosas. All of the gastric carcinoma cell lines expressed mRNA for EGFR and TGF-alpha genes. TMK-1 and MKN-28 cells also expressed EGF mRNA. Production of EGF, TGF-alpha and EGFR protein by gastric carcinoma cell lines was also confirmed by EGF and TGF-alpha specific monoclonal antibody binding. As for surgical specimens, EGFR and TGF-alpha mRNA were detected at high levels in all the tumor tissues. Interestingly, EGF mRNA was detected in 5 (33.3%) of the 15 gastric carcinomas but it was not detected in normal tissues. Moreover, anti-EGF and anti-TGF-alpha monoclonal antibodies inhibited the spontaneous 3H-TdR uptake by gastric carcinoma cells. These results suggest that EGF and/or TGF-alpha produced by tumor cells act as autocrine growth factors for gastric carcinomas. PMID- 2108947 TI - Changes in serum and tissue carcinoembryonic antigen with growth of a human gastric cancer xenograft in nude mice. AB - We established a human gastric cancer xenograft which, when inoculated into nude mice, showed a positive correlation between tumor growth and the serum level of carcinoembryonic antigen (CEA). Serum CEA levels in the mice rose continuously with increasing tumor weight after inoculation, showing a correlation coefficient of 0.96. A positive correlation was also observed between the tissue CEA level and tumor weight, the former increasing along with the latter. Furthermore, the level of serum CEA closely paralleled that of tissue CEA. The serum CEA level fell after tumor extirpation, with a half-life of approximately 86 h. These results suggest that the elevation of serum CEA is attributable to the gain in tumor weight as well as the increase of CEA production in the tumor tissue. Thus, human gastric cancer xenografts in nude mice are a good model for examining the biological role of CEA. PMID- 2108948 TI - Identification of a protein increasing in serum of Nagase analbuminemic rats bearing intestinal tumors as an isotype of T-kininogen. AB - Increase in an unidentified protein was observed in serum of Nagase analbuminemic rats (NAR) bearing intestinal tumors induced by azoxymethane. This protein seemed to be a polymer of a protein of 73 kDa as estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and so was tentatively named 73K-protein. The serum concentration of 73K-protein in NAR bearing intestinal tumors was 11.9 +/- 2.2 mg/ml (mean +/- SD, n = 5), whereas that in control NAR was 2.0 +/- 0.2 mg/ml. Increase of the serum 73K-protein level was also observed in Sprague Dawley rats bearing intestinal tumors, skin tumors, subcutaneous sarcomas, or mammary tumors and in ACI rats bearing urinary bladder tumors. On double immunodiffusion analysis, the 73K-protein was not detected in mouse, guinea pig, pig, horse, or human serum. A cDNA clone bearing the sequence encoding 73K protein was isolated from a cDNA library constructed from rat liver mRNA. The nucleotide sequence of the 73K-protein showed 98.8% and 96.9% homologies with the sequences of the 3'-proximal domains of the cDNAs for TI- and TII-kininogen, respectively. Therefore, the 73K-protein was concluded to be an isotype of T kininogen. PMID- 2108949 TI - Enhancement of polymorphonuclear leukocyte-mediated tumor cytotoxicity by serum factor(s). AB - It has been reported that beta-1,3-D-glucan isolated from Alcaligenes faecalis (TAK) promoted tumor cytolysis by mouse polymorphonuclear leukocytes (PMN). We investigated the effect of serum on mouse PMN tumor cytolysis induced by TAK and other PMN stimulators. Addition of fetal calf serum (FCS) to the cytolysis assay enhanced tumor cytolysis by PMN in a dose-dependent manner. Sera obtained from horses, mice, and rats were also effective enhancers of PMN tumor cytolysis. When FCS was added after the assay was under way, the enhancing effect decreased proportionally to the time elapsed. The enhancing activity was detected over a broad range of fractions with a peak at 170 kD by fractionation on a Superose 6 column. The responsible factor(s) in serum was stable after treatment at 60 degrees C, 30 min or after lowering the pH to 2. Mouse PMN stimulated with TAK increased production of hydrogen peroxide in the presence of FCS. PMID- 2108950 TI - Enhancement of the antibody-dependent tumoricidal activity of human monocytes by human monocytic colony-stimulating factor. AB - Human monocytic colony-stimulating factor (hM-CSF) stimulates mature cells as well as progenitor cells of human monocyte lineage. In the present study, we investigated the effect of completely purified native hM-CSF on the tumoricidal activity of human monocytes against Raji (Burkitt lymphoma-derived cell line) using a chromium release assay. Preincubation of human peripheral blood monocytes with hM-CSF for 48 h markedly enhanced their antibody-dependent cellular cytotoxicity (ADCC). This enhancing effect was dependent on the concentration of hM-CSF, and maximal enhancement was achieved at the concentration of 66 ng/ml. The number of receptor sites on monocytes against the Fc portion of immunoglobulin G increased 2- to 4-fold during 48 h incubation with hM-CSF. These results suggest that hM-CSF stimulates monocyte-ADCC by increasing the number of Fc receptor sites on human monocytes. PMID- 2108951 TI - Methotrexate cytotoxicity as related to irreversible S phase arrest in mouse L1210 leukemia cells. AB - The association between cytotoxicity and cell cycle perturbation caused by methotrexate (MTX) was investigated in mouse L1210 leukemia cells by flow cytometric bromodeoxyuridine/DNA assay. In the range of concentrations of MTX from 10(-7) M to 10-6) M, in vitro exposure to the drug for 6 h caused a dose dependent suppression of clonal growth of the tumor cells and S phase arrest in the cycle progression, resulting in an accumulation of cells in early S phase, in which they showed no definite increase of DNA content above G1 levels. The surviving fraction of the clonogenic cells corresponded with the fraction of cells which recovered from the S phase arrest in MTX-free medium. In mice bearing L1210 ascites tumors, a bolus injection of MTX caused the S phase arrest of the tumor cells as shown in suspension cultures, and cytokinetic recovery was observed in parallel with the regrowth of the tumor. These results showed that irreversible S phase arrest is a critical cytokinetic event associated with the cytotoxicity of MTX. PMID- 2108953 TI - Comparison of two carbapenems, SM-7338 and imipenem: affinities for penicillin binding proteins and morphological changes. AB - We investigated the binding affinities of SM-7338 for penicillin-binding proteins (PBPs) and the morphological changes induced by it compared with those of imipenem. Both SM-7338 and imipenem had the highest binding affinities for PBP-2 of Escherichia coli, which were in good agreement with the primary morphological response of spherical cell formation. SM-7338 also showed high affinities for PBP 1A, -1Bs, and -3, and imipenem showed high affinities for PBP-1A and -1Bs but not for PBP-3. At 4-fold MIC, SM-7338 induced a indeterminate form, whereas imipenem did not. This may be due to the higher affinity of SM-7338 for PBP-3 compared to that of imipenem. Against Pseudomonas aeruginosa, SM-7338 had very high affinities for PBP-2 and -3, and imipenem had higher affinities for PBP-2 and 1A. SM-7338 induced this organism to filamentous cells at a concentration lower than its MIC, bulge cells at 2-fold MIC, and spherical cells at 4-fold MIC, while imipenem principally induced round cell formation at each concentration. These morphological differences in P. aeruginosa may be due to the differences in binding profiles to PBPs. We also studied the affinities for PBPs using radioactive SM-7338. The data obtained supported these results. PMID- 2108952 TI - Immunoglobulins in Hassall's corpuscles of the human thymus. AB - Ninety nine human thymuses were examined immunohistochemically for the presence of immunoglobulins G, A, M. D and E, light-chains, secretory component and albumin in the cells of Hassall's corpuscles. Igs G, A, M and secretory component were present. These showed a rise after birth until the age of 20 years and also increased with the degree of involution, falling when involution became complete. Albumin was also consistently demonstrated. There was a degree of correlation between the presence of Igs and production of Igs G, A and M by plasma cells in the thymic medulla. There was a close correlation between the amounts of IgA and secretory component in the cells of Hassall's corpuscles and the thymus may have to be regarded as a part of the secretory-IgA system. Light chains of the immunoglobulin molecule were also present, with lambda predominating over kappa, possibly reflecting the same kappa/lambda ratio found with thymic immunoglobulin production. No IgD or IgE was demonstrated. The presence of albumin may represent a passive uptake of protein in senescent cells but a more active uptake of Igs, particularly IgG and IgA, could be postulated. The production of Igs in the thymus and their presence in Hassall's corpuscles could be of significance in the maturation and regulation of the immune response. PMID- 2108954 TI - Personal hygiene in external genitalia of healthy and hospitalized elderly women. AB - A comparative study of the personal hygiene of two groups of elderly women was carried out in Orebro, Sweden. The investigation group consisted of 28 women who were hospitalized in long-term care wards and the comparison group consisted of 35 healthy women. The results show that a remainder of soap in the genitalia may be one factor contributing to elderly hospitalized women's discomfort. Caregivers should be educated in how to assist elderly hospitalized women with their personal hygiene. PMID- 2108955 TI - Factors influencing optimization of diffusion assays for antibiotics. AB - Agar nutrient content, cylinder charge volume, thickness (volume) of the agar layer, and incubation temperature were 4 factors varied to determine their effect(s) on the optimization of the cylinder-plate diffusion assay. Chlortetracycline was the pilot antibiotic and Bacillus cereus was used as the assay organism. Zones of inhibition were larger when the incubation temperature was lower than that which was commonly used and/or when the nutrient level was decreased; the zones were smaller when the incubation temperature was raised and/or when an increased nutrient level was used. The thickness (volume) of the assay layer played the most important role; the thinner the layer the less the effect the cylinder charge volume had on the zone diameter. The slopes of the response lines were minimally affected by cylinder charge volume. For a 7 mL assay layer per standard Petri plate, cylinder charge volumes ranging from 150 to 250 microL had little effect on zone diameter. The linearity of the response line was unaffected by assay layer thickness (volume), nutrient level, temperature of incubation, or cylinder charge volume. As long as the conditions for the assay were standardized, there were no discernible effects on recoveries or potencies. PMID- 2108956 TI - Two sisters with Rett syndrome. AB - We present the clinical histories and physical findings of two sisters with Rett syndrome. The physical examination, combined with a review of their medical charts, revealed that both patients met the necessary criteria for the diagnosis of Rett syndrome as defined by the Rett syndrome diagnostic criteria work group. The older sister, currently 25 years of age, is typically affected, whereas the younger sister, currently 22 years of age, is affected with a seizure disorder showing an unusually early onset. PMID- 2108957 TI - Zinc fingers and other metal-binding domains. Elements for interactions between macromolecules. PMID- 2108958 TI - A-type ATP binding consensus sequences are critical for the catalytic activity of the calmodulin-sensitive adenylyl cyclase from Bacillus anthracis. AB - Analysis of the predicted amino acid sequence of Bacillus anthracis adenylyl cyclase revealed sequences with homology to consensus sequences for A- and B-type ATP binding domains found in many ATP binding proteins. Based on the analysis of nucleotide binding proteins, a conserved basic amino acid residue in the A-type consensus sequence and a conserved acidic amino acid residue in the B-type consensus sequence have been implicated in the binding of ATP. The putative ATP binding sequences in the B. anthracis adenylyl cyclase possess analogous lysine residues at positions 346 and 353 within two A-type consensus sequences and a glutamate residue at position 436 within a B-type consensus sequence. The two A type consensus sequences overlap each other and have the opposite orientation. To determine whether Lys-346, Lys-353, or Glu-436 of the B. anthracis adenylyl cyclase are crucial for enzyme activity, Lys-346 and Lys-353 were replaced with methionine and Glu-436 with glutamine by oligonucleotide-directed mutagenesis. Furthermore, Lys-346 was also replaced with arginine. The genes encoding the wild type and mutant adenylyl cyclases were placed under the control of the lac promoter for expression in Escherichia coli, and extracts were assayed for adenylyl cyclase activity. In all cases, a 90-kDa polypeptide corresponding to the catalytic subunit of the enzyme was detected in E. coli extracts by rabbit polyclonal antibodies raised against the purified B. anthracis adenylyl cyclase. The proteins with the Lys-346 to methionine or arginine mutations exhibited no adenylyl cyclase activity, indicating that Lys-346 in the A-type ATP binding consensus sequence plays a critical role for enzyme catalysis. Furthermore, the enzyme with the Lys-353 to methionine mutation was also inactive, suggesting that Lys-353 may also directly contribute to enzyme catalysis. In contrast, the protein with the Glu-436 to glutamine mutation retained 75% of enzyme activity, suggesting that Glu-436 in the B-type ATP binding consensus sequence may not be directly involved in enzyme catalysis. It is concluded that Lys-346 and Lys-353 in B. anthracis adenylyl cyclase may interact directly with ATP and contribute to the binding of the nucleotide to the enzyme. PMID- 2108959 TI - Calcium- and magnesium-binding properties of oncomodulin. Direct binding studies and microcalorimetry. AB - Ca2+ binding to the wild type recombinant oncomodulin was studied by equilibrium flow dialysis in the absence and presence of 1, 2, and 10 mM Mg2+. Direct Mg2(+) binding experiments were carried out by the Hummel-Dryer gel filtration technique. These studies revealed that in the absence of Mg2+ oncomodulin binds two Ca2+ with KCa = 2.2 x 10(7) and 1.7 x 10(6) M-1, respectively. In the absence of Ca2+ the protein binds only one Mg2+ with KMg = 4.0 x 10(3) M-1.Mg2+ antagonizes Ca2+ binding at the high affinity site according to the rule of direct competition. Ca2+ binding to the low affinity site is only slightly affected by Mg2+, so that in the presence of 2-3 mM Mg2+ the two sites have apparently an equal affinity for Ca2+. Microcalorimetry showed that, in spite of the different affinities of the two Ca2(+)-binding sites, delta H0 for the binding of each Ca2+ is identical and exothermic for -18.9 kJ/site. It follows that the entropy gain upon binding of Ca2+ is +77.1 J K-1 site-1 for the high affinity Ca2(+)-Mg2+ site and +56.0 J K-1 site-1 for the low affinity Ca2(+) specific site. Mg2+ binding is endothermic for +13 kJ/site with an entropy change of +111 J K-1 site-1. The thermodynamic characteristics of the Ca2(+)-Mg2+ site resemble most those of site II (the so-called EF domain) of toad alpha parvalbumin. The characteristics of Ca2+ binding to the specific site (likely the CD domain) are different from those of the Ca2+ specific sites in troponin C and in calmodulin and suggest that in oncomodulin hydrophobic forces do not play a predominant role in the binding process at the specific site. PMID- 2108960 TI - Predominant structural features of the cell wall arabinogalactan of Mycobacterium tuberculosis as revealed through characterization of oligoglycosyl alditol fragments by gas chromatography/mass spectrometry and by 1H and 13C NMR analyses. AB - The peptidoglycan-bound arabinogalactan of a virulent strain of Mycobacterium tuberculosis was per-O-methylated, partially hydrolyzed with acid, and the resulting oligosaccharides reduced and O-pentadeute-rioethylated. The per-O alkylated oligoglycosyl alditol fragments were separated by high pressure liquid chromatography and the structures of 43 of these constituents determined by 1H NMR and gas chromatography/mass spectrometry. The arabinogalactan was shown to consist of a galactan containing alternating 5-linked beta-D-galactofuranosyl (Galf) and 6-linked beta-D-Galf residues. The arabinan chains are attached to C-5 of some of the 6-linked Galf residues. The arabinan is comprised of at least three major structural domains. One is composed of linear 5-linked alpha-D arabinofuranosyl (Araf) residues; a second consists of branched 3,5-linked alpha D-Araf units substituted with 5-linked alpha-D-Araf residues at both branched positions. The non-reducing terminal region of the arabinan was characterized by a 3,5-linked alpha-D-Araf residue substituted at both branched positions with the disaccharide beta-D-Araf-(1----2)-alpha-D-Araf. 13C NMR of intact soluble arabinogalactan established the presence of both alpha- and beta-Araf residues in this domain. This non-reducing terminal motif apparently provides the structural basis of the dominant immunogenicity of arabinogalactan within mycobacteria. A rhamnosyl residue occupies the reducing terminus of the galactan core and may link the arabinogalactan to the peptidoglycan. Evidence is also presented for the presence of minor structural features involving terminal mannopyranosyl units. Models for most of the heteropolysaccharide are proposed which should increase our understanding of a molecule responsible for much of the immunogenicity, pathogenicity, and peculiar physical properties of the mycobacterial cell. PMID- 2108961 TI - Cloning, genetic organization, and characterization of a structural gene encoding bacillopeptidase F from Bacillus subtilis. AB - Bacillopeptidase F is an extracellular serine protease that is expressed at the beginning of the stationary phase. To study its structure, regulation of expression, and physiological roles, we have cloned and characterized the structural gene (bpf) encoding this protease from Bacillus subtilis. DNA sequence analysis suggests this protease is synthesized as a preproenzyme (Mr = 92,000). Through processing at both the NH2 and COOH termini, it is gradually converted into various forms with molecular mass ranging from 80 to 48 kDa. Shortening the 3' end of bpf demonstrates that at least 290 amino acid residues from the COOH terminus of bacillopeptidase F are not required for either catalytic activity or secretion. Bacillopeptidase F exhibits sequence similarity with several serine proteases. Its gene is found immediately downstream from the fts operon which was mapped at 135 degrees on the B. subtilis genetic linkage map. Inactivation of the chromosomal copy of bpf shows no effect on cell growth and sporulation. A triple protease-deficient strain (WB300 with the structural genes for bacillopeptidase F and two other major proteases inactivated) was constructed to serve as a better expression host for the production and secretion of foreign proteins. PMID- 2108962 TI - Enhancement of the thermostability of subtilisin E by introduction of a disulfide bond engineered on the basis of structural comparison with a thermophilic serine protease. AB - Sites for Cys substitutions to form a disulfide bond were chosen in subtilisin E from Bacillus subtilis, a cysteine-free bacterial serine protease, based on the structure of aqualysin I of Thermus aquaticus YT-1 (a thermophilic subtilisin type protease containing two disulfide bonds). Cys residues were introduced at positions 61 (wild-type, Gly) and 98 (Ser) in subtilisin E by site-directed mutagenesis. The Cys-61/Cys-98 mutant subtilisin appeared to form a disulfide bond spontaneously in the expression system used and showed a catalytic efficiency equivalent to that of the wild-type enzyme for hydrolysis of a synthetic peptide substrate. The thermodynamic characteristics of these enzymes were examined in terms of enzyme autolysis (t1/2) and thermal stability (Tm). The half-life of the Cys-61/Cys-98 mutant was found to be 2-3 times longer than that of the wild-type enzyme. Similar results were obtained by differential scanning calorimetry. The disulfide mutant showed a Tm of 63.0 degrees C, which was 4.5 degrees C higher than that observed for the wild-type enzyme. Under reducing conditions, however, the characteristics of the mutant enzyme were found to revert to those of the wild-type enzyme. These results strongly suggest that the introduction of a disulfide bond by site-directed mutagenesis enhanced the thermostability of subtilisin E without changing the catalytic efficiency of the enzyme. PMID- 2108963 TI - Phosphorylation of synapsin I at a novel site by proline-directed protein kinase. AB - Previous studies identified synapsin I as a potential substrate for a newly discovered growth factor-sensitive, proline-directed protein kinase originally isolated from rat pheochromocytoma. The present study describes the site-specific phosphorylation of synapsin I by highly purified preparations of proline-directed protein kinase. The incorporation of [32P]phosphate into bovine brain synapsin I was dependent upon both the amount of kinase present and the time of incubation. The maximum stoichiometry of phosphorylation approached 1 mol of phosphate/mol of synapsin I protein. When analyzed by sodium dodecyl sulfate-gel electrophoresis and autoradiography, [32P]phosphate was found to be incorporated into both synapsin Ia and Ib. Phosphoamino acid analysis demonstrated that serine residues were phosphorylated exclusively. Digestion of phosphorylated synapsin I with trypsin followed by high performance liquid chromatography (HPLC) phosphopeptide analysis indicated that the tryptic peptide containing the major phosphorylation site eluted as a single peak at approximately 17% acetonitrile. The primary structure of this phosphopeptide, determined by gas-phase sequencing, was found to be Gln-Ser-Arg-Pro-Val-Ala-Gly-Gly-Pro-Gly-Ala-Pro-Pro-Ala-Thr-Arg-Pro-Pro- Ala-Ser-Pro-Ser-Pro-Gln-Arg. Sequential Edman degradation of this HPLC-purified tryptic phosphopeptide revealed that serine 20 of this peptide was the major phosphorylated residue. This phosphoacceptor site is immediately flanked by a carboxyl-terminal proline residue, an observation that further verifies the proline-directed nature of this protein kinase. The tryptic phosphopeptide corresponds exactly to a sequence in the collagenase-sensitive, proline-rich "tail" region of bovine synapsin I. This novel phosphorylation site is close to but distinct from phosphorylation sites 2 and 3, which are known to be phosphorylated by calcium/calmodulin-dependent protein kinase II and are considered to be of regulatory importance. PMID- 2108964 TI - Effects of substitution of threonine 654 of the epidermal growth factor receptor on epidermal growth factor-mediated activation of phospholipase C. AB - Addition of epidermal growth factor (EGF) to many cell types activates phospholipase C resulting in increased levels of diacylglycerol and intracellular Ca2+ which may lead to activation of protein kinase C. EGF treatment of cells can also lead to phosphorylation of the EGF receptor at threonine 654 (a protein kinase C phosphorylation site) which appears to attenuate some aspects of receptor signaling. Thus, a feedback loop involving the EGF receptor, phospholipase C, and protein kinase C may regulate EGF receptor function. In this report, the role of phosphorylation of threonine 654 of the EGF receptor in regulation of EGF-stimulated activation of phospholipase C was investigated. NIH 3T3 cells expressing the normal human EGF receptor or expressing EGF receptor in which an alanine residue had been substituted at residue 654 of the receptor were used. Addition of EGF to cells expressing wild-type receptor induced a rapid, but transient, increase in phosphorylation of threonine 654. EGF addition also caused the rapid accumulation of inositol phosphates in these cells. EGF-stimulated accumulation of inositol phosphates was significantly higher in cells expressing Ala-654 receptors compared to control cells. Treatment of cells with 12-O tetradecanoylphorbol 13-acetate (TPA), which stimulated phosphorylation of threonine 654 to a greater degree than EGF, completely inhibited EGF-dependent inositol phosphate accumulation in cells expressing wild-type receptor, but caused only a 20-30% inhibition in Ala-654 expressing cells. EGF stimulated phosphorylation of phospholipase C-gamma on serine and tyrosine residues in cells expressing wild-type of Ala-654 receptors. However, TPA treatment of cells inhibited EGF-induced tyrosine phosphorylation of phospholipase C-gamma only in cells expressing wild-type receptors. Similarly, TPA inhibited tyrosine-specific autophosphorylation of the EGF receptor and tyrosine phosphorylation of several other proteins in wild-type receptor cells, but not in Ala-654 cells. TPA treatment abolished high affinity binding of EGF to cells expressing wild-type receptors, while decreasing the number of high affinity binding sites 20-30% in Ala-654 cells. These data suggest that phosphorylation of threonine 654 can regulate early events in EGF receptor signal transduction such as phosphoinositide turnover, probably through a feedback mechanism involving protein kinase C. Subsequent dephosphorylation of threonine 654 could reactivate the EGF receptor for participation in later signaling events. PMID- 2108965 TI - Interferon gamma and interleukin 2 synergize to induce selective monokine expression in murine peritoneal macrophages. AB - We have examined the effects of interleukin 2 (IL-2) treatment either alone or in combination with interferon (IFN) gamma or beta on the expression of several activation associated genes (e.g. tumor necrosis factor alpha (TNF alpha), IFN inducible 10-kDa protein (IP-10] in murine peritoneal macrophages. IL-2 alone did not induce the expression of either gene while IFN gamma or IFN beta had a modest inductive effect on IP-10 but no effect on TNF alpha expression. When either form of IFN was used in combination with IL-2 there was a marked synergistic induction of both mRNAs. IFN gamma and IL-2 were maximally effective when both agents were added simultaneously, and induced mRNA expression declined over a 24-h period in cells pretreated with IFN gamma prior to addition of IL-2. Expression of both genes following combination lymphokine treatment was mediated by increased transcriptional activity. The responses to all three lymphokines were dose dependent; the concentration requirement for IL-2 indicated interaction with an intermediate or low affinity receptor. The expression of both monokine genes was transient and was comparable although not identical to that seen in cells stimulated with lipopolysaccharide. IFN gamma and IL-2 could synergize to stimulate the expression of either TNF alpha or IP-10 mRNA using sequential non overlapping treatment periods regardless of the order in which the two stimuli were applied to the cells. The effect of either agent alone induced a transient (1-5 h) responsive state with respect to subsequent stimulation with the second agent. Expression of both monokine genes in response to IFN gamma/IL-2 treatment was independent of protein synthesis as cycloheximide did not inhibit the accumulation of specific mRNA. Interestingly, the combination of IL-2 and cycloheximide was as effective as IFN gamma and IL-2 together. In concert, these results indicate that both IFN and IL-2 generate independent intracellular signals which alone are incapable of inductive effect but which are potent activators of inflammatory gene expression when coincidentally expressed. PMID- 2108966 TI - Frameshift and nonsense mutations in a human genomic sequence homologous to a murine UDP-Gal:beta-D-Gal(1,4)-D-GlcNAc alpha(1,3)-galactosyltransferase cDNA. AB - We have previously isolated a murine UDP-Gal:beta-D-Gal(1,4)-D-GlcNAc alpha(1,3) galactosyltransferase (alpha(1,3)-GT) cDNA (Larsen, R. D., Rajan, V. P., Ruff, M. M., Kukowska-Latallo, J., Cummings, R. D., and Lowe, J. B. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 8227-8231). This enzyme constructs the terminal alpha(1,3)-galactosyl linkage within the epitope Gal alpha 1----3Gal. This epitope is expressed by New World monkeys and many nonprimate mammals but generally not by Old World primates, anthropoid apes, or man. To investigate the molecular basis for the apparent species-specific absence of this enzyme and its oligosaccharide product, we have sequenced a human genomic DNA fragment homologous to the murine alpha(1,3)-GT cDNA. This fragment contains a 703 nucleotide region that shares 82% identity with a region of the murine cDNA encoding part of the enzyme's catalytic domain. The human sequence, however, has suffered deletion of single nucleotides at two separate positions, relative to the murine sequence. These frameshift mutations disrupt the translational reading frame that would otherwise maintain a 76% amino acid sequence identity between the human sequence and the murine alpha(1,3)-GT. Moreover, nonsense mutations exist within this disrupted reading frame that would truncate the human polypeptide, relative to the murine enzyme. We therefore propose that this human sequence represents a pseudogene and cannot determine expression of Gal alpha 1-- -3Gal epitopes on human cells. PMID- 2108967 TI - Intercellular variation in levels of adducts of aflatoxin B1 and G1 in DNA from rat tissues: a quantitative immunocytochemical study. AB - Adducts between aflatoxin B1 and G1 and DNA have been visualised and quantified in various rat tissues by a sensitive immunocytochemical approach. The quantitative validity of this assay has been examined by comparison with experiments using radioactively labelled aflatoxin. Rats were exposed to single and multiple doses of aflatoxin and a marked intercellular variation in adduct levels was observed in kidney and lung, in contrast to the liver, where binding was more homogeneous. No adducts were detected in the oesophagus, forestomach, colon, spleen or testes (detection limit approximately 300 pg aflatoxin/mg DNA). The DNA adduct data are discussed in relation to the carcinogenicity of aflatoxin B1 and G1. PMID- 2108968 TI - A 39-kD plasma membrane protein (IP39) is an anchor for the unusual membrane skeleton of Euglena gracilis. AB - The major integral plasma membrane protein (IP39) of Euglena gracilis was radiolabeled, peptide mapped, and dissected with proteases to identify cytoplasmic domains that bind and anchor proteins of the cell surface. When plasma membranes were radioiodinated and extracted with octyl glucoside, 98% of the extracted label was found in IP39 or the 68- and 110-kD oligomers of IP39. The octyl glucoside extracts were incubated with unlabeled cell surface proteins immobilized on nitrocellulose (overlays). Radiolabel from the membrane extract bound one (80 kD) of the two (80 and 86 kD) major membrane skeletal protein bands. Resolubilization of the bound label yielded a radiolabeled polypeptide identical in Mr to IP39. Intact plasma membranes were also digested with papain before or after radioiodination, thereby producing a cytoplasmically truncated IP39. The octyl glucoside extract of truncated IP39 no longer bound to the 80-kD membrane skeletal protein in the nitrocellulose overlays. EM of intact or trypsin digested plasma membranes incubated with membrane skeletal proteins under stringent conditions similar to those used in the nitrocellulose overlays revealed a partially reformed membrane skeletal layer. Little evidence of a membrane skeletal layer was found, however, when plasma membranes were predigested with papain before reassociation. A candidate 80-kD binding domain of IP39 has been tentatively identified as a peptide fragment that was present after trypsin digestion of plasma membranes, but was absent after papain digestion in two-dimensional peptide maps of IP39. Together, these data suggest that the unique peripheral membrane skeleton of Euglena binds to the plasma membrane through noncovalent interactions between the major 80-kD membrane skeletal protein and a small, papain sensitive cytoplasmic domain of IP39. Other (62, 51, and 25 kD) quantitatively minor peripheral proteins also interact with IP39 on the nitrocellulose overlays, and the possible significance of this binding is discussed. PMID- 2108972 TI - Multidimensional assessment of the elderly. PMID- 2108969 TI - Cytoskeletal control of centrioles movement during the establishment of polarity in Madin-Darby canine kidney cells. AB - The two centrioles that are localized close to each other and to the nucleus in single Madin-Darby Canine kidney cells (MDCK) move apart by distances as large as 13 microns after the establishment of extensive cellular junctions. Microfilaments, and possibly microtubules appear to be responsible for this separation. In fully polarized cells, the centrioles are localized just beneath the apical membrane. After disruption of intercellular junctions in low calcium medium, the centrioles move back towards the cell center. This process requires intact microtubules but happens even in the absence of microfilaments. These results indicate that the position of centrioles is determined by opposing forces produced by microtubules and microfilaments and suggest that the balance between these forces is modulated by the assembly of cellular junctions. Centriole separation appears to be an early event in the process that precedes their final positioning in the apical-most region of the polarized cell. PMID- 2108970 TI - Differential distribution of subsets of myofibrillar proteins in cardiac nonstriated and striated myofibrils. AB - Cultured cardiac myocytes were stained with antibodies to sarcomeric alpha actinin, troponin-I, alpha-actin, myosin heavy chain (MHC), titin, myomesin, C protein, and vinculin. Attention was focused on the distribution of these proteins with respect to nonstriated myofibrils (NSMFs) and striated myofibrils (SMFs). In NSMFs, alpha-actinin is found as longitudinally aligned, irregular approximately 0.3-microns aggregates. Such aggregates are associated with alpha actin, troponin-I, and titin. These I-Z-I-like complexes are also found as ectopic patches outside the domain of myofibrils in close apposition to the ventral surface of the cell. MHC is found outside of SMFs in the form of discrete fibrils. The temporal-spatial distribution and accumulation of the MHC-fibrils with respect to the I-Z-I-like complexes varies greatly along the length of the NSMFs. There are numerous instances of I-Z-I-like complexes without associated MHC-fibrils, and also cases of MHC-fibrils located many microns from I-Z-I-like complexes. The transition between the terminal approximately 1.7-microns sarcomere of any given SMF and its distal NSMF-tip is abrupt and is marked by a characteristic narrow alpha-actinin Z-band and vinculin positive adhesion plaque. A titin antibody T20, which localizes to an epitope at the Z-band in SMFs, precisely costains the 0.3-microns alpha-actinin aggregates in ectopic patches and NSMFs. Another titin antibody T1, which in SMFs localizes to an epitope at the A-I junction, typically does not stain ectopic patches and NSMFs. Where detectable, the T1-positive material is adjacent to rather than part of the 0.3 microns alpha-actinin aggregates. Myomesin and C-protein are found only in their characteristic sarcomeric locations (even in just perceptible SMFs). These A-band associated proteins appear to be absent in ectopic patches and NSMFs. PMID- 2108971 TI - Terminal differentiation of ectodermal epithelial stem cells of Hydra can occur in G2 without requiring mitosis or S phase. AB - Using bromodeoxyuridine incorporation to label cells in S phase we found that ectodermal epithelial cells of Hydra can start and complete their terminal differentiation in the G2 phase of the cell cycle. Most of the cells traversed their last S phase before the signal for differentiation, namely excision of head or foot, was given. The S phase inhibitor aphidicolin accordingly did not inhibit head or foot specific differentiation. The results show that differentiation to either head- or foot-specific ectodermal epithelial cells can start and is completed within the same G2 phase. This is therefore the first description of a complete differentiation from a population of proliferating cells to terminally differentiated, cell cycle-arrested cells without the necessity of passing through an S phase or mitosis. PMID- 2108973 TI - Harlem, Bangladesh, and physician responsibility. PMID- 2108974 TI - Flights of fancy. PMID- 2108975 TI - Syncope and bigeminal rhythm. PMID- 2108976 TI - Management of tachyarrhythmias after MI. AB - The prognostic significance of ventricular and supraventricular tachyarrhythmias after infarction varies with type and timing. In some cases intervention may be appropriate, and in others not. Management of peri-infarction and of later arrhythmias is reviewed. To avoid proarrhythmic consequences, pharmacologic treatment should be rigorously guided by carefully defined end points. PMID- 2108977 TI - Congestive heart failure in a middle-aged man. PMID- 2108978 TI - Immunotherapy of IgE-mediated disease. AB - Although immunotherapy has a long record of efficacy in certain allergies, its safety has recently been questioned. One problem is that physicians trained and certified in allergy are not the only ones who prescribe and administer allergen injections. Fundamental issues of diagnosis, patient and allergen selection, and management of adverse reactions are reviewed. PMID- 2108979 TI - Modern approaches to bile acid transport proteins. AB - New techniques for studying solute uptake across epithelial membranes in the gut are providing a clearer picture of bile acid handling. In the small intestine, liver, and other sites, membrane proteins that mediate active bile acid transport are key players. Better understanding of these transporters may lead to elucidation of disorders of bile handling and better treatment of such disorders. PMID- 2108980 TI - Chromatographic studies on the binding, action and metabolism of (-)-deprenyl. AB - Serum binding, the effect on striatal dopamine release and the metabolism of (-) deprenyl [N-methyl-N-propargyl(2-phenyl-1-methyl)ethylammonium chloride], TZ-650 [N-methyl-N-propargyl(2-phenyl)ethylammonium chloride] and J-508 [N-methyl-N propargyl(indanyl)ammonium chloride] were investigated using various chromatographic methods. A strong interaction between (-)-deprenyl and macroglobulins was found. Deprenyl enhanced the dopamine release from striatal slices of the rat brain and also inhibited the dopamine-DOPAC conversion. Deprenyl analogues showed either smaller or no effect. Hydroxylation of (-) deprenyl takes place in the para position, in addition to the usual oxidative N dealkylations, which are known from various metabolic studies on N-substituted phenylalkylamines. PMID- 2108981 TI - Combined luteinizing hormone releasing hormone analogue and exogenous gonadotrophins for the treatment of infertility associated with polycystic ovaries. AB - This study was designed to compare the results of treatment with, firstly, exogenous gonadotrophins, with (57 cycles) and without (65 cycles) pretreatment with a superactive analogue of luteinizing hormone releasing hormone (LHRH) and, secondly, pure follicle stimulating hormone (FSH) (50 cycles) with those of human menopausal gonadotrophin (HMG) (72 cycles) in 46 women with clomiphene-citrate resistant anovulation associated with polycystic ovaries. Patients randomly allocated to the analogue group received buserelin (Suprefact, Hoechst, UK, Ltd, Hounslow, Middlesex), 800 micrograms/day by nasal insufflation and when hypogonadism was achieved, patients were again randomly allocated for ovarian stimulation with either FSH or HMG. Controls received FSH or HMG alone. Patients pretreated with the analogue had similar pregnancy and ovulation rates, needed larger doses and more days of gonadotrophin therapy and had more ovarian overstimulation than those receiving no pretreatment. The role of superactive LHRH analogues for induction of a single ovulation for in-vivo fertilization is thus uncertain. Pure FSH had no advantages over HMG, the LH content of HMG having no deleterious effect on the ovary. PMID- 2108982 TI - Treatment of hyperstimulation during in-vitro fertilization. AB - In 33 patients treated with a combination of an LHRH agonist (LHRH-A) and gonadotrophin in a long protocol, a biological hyperstimulation occurred (E2 greater than 2500 pg/ml on the day of HCG administration and 4722 +/- 1190 pg/ml the day after, with greater than 10 follicles greater than 12 mm on each ovary). The replacement of fresh embryos were deferred and LHRH-A was continued, and an endometrial biopsy was performed on the theoretical day of replacement (2 days after oocyte recovery). With this technique, we obtained a mean number of 17.9 +/ 7 oocytes, a fertilization rate of 49% and a replacement rate of 87% in a deferred cycles. The overall pregnancy rate of frozen-thawed embryos was 27% in the seven spontaneous cycles, 12 induced cycles and 10 artificial cycles. Only one severe hyperstimulation occurred and this case emphasizes that caution remains necessary even with this technique. PMID- 2108983 TI - Antiphospholipid antibodies in unselected patients with repeated abortion. AB - We have studied, prospectively, the incidence of several antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-phosphatidylserine, anti phosphatidic acid, anti-phosphatidylinositol and anti-thromboplastin antibodies) in 65 consecutive patients with two or more (range 2-8, mean 3.1) abortions. Lupus anticoagulant activity was detected in seven (10.7%) patients and all of them exhibited other antiphospholipid antibodies. Of the previous pregnancies in these seven women, 88% had ended in spontaneous abortion. Four of them achieved pregnancy after low-dose aspirin therapy was started, and carried successfully to term. It is concluded that antiphospholipid antibodies, namely lupus anticoagulant, should be routinely screened in the recurrent spontaneous aborter. PMID- 2108984 TI - Influence of the duration of the oestradiol rise on the success rate in GnRH analogue/HMG-stimulated IVF cycles. AB - The influence of the duration of the serum oestradiol (E2) rise before human chorionic gonadotrophin (HCG) injection on the outcome of in-vitro fertilization (IVF) cycles was investigated. Two different stimulation protocols were compared. In 218 cycles, the Norfolk protocol for stimulation with human menopausal gonadotrophin (HMG) was used (protocol A). In 235 cycles, pituitary function was suppressed by a single injection of a long-acting GnRH analogue ('Decapeptyl microcapsules') before HMG stimulation was started (protocol B). The overall pregnancy rates were significantly higher with protocol B (22% per puncture, 21% per started cycle) than with protocol A (14% per puncture, 9% per started cycle). For each interval of E2 rise duration (5-11 days), the fertilization rates (per oocyte) and the pregnancy rates (per puncture) were evaluated. There was a clear cut maximum of the pregnancy rates for 6 and 7 days of E2 rise (21 and 16% respectively) for protocol A. For protocol B, pregnancy rates were generally higher than for protocol A. There was also a maximum of the pregnancy rates for 6 (32%) and 7 (29%) days of E2 rise but this maximum was not as clear-cut as for protocol A. The fertilization rates showed no significant differences for each interval of E2 rise in both groups (between 63 and 89%). Therefore, it is concluded that endometrial maturity, and not the oocyte's ability for fertilization, is the most critical factor for success in IVF cycles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2108985 TI - Transfers of frozen-thawed human embryos in cycles stimulated by HMG. AB - A total of 130 transfers of frozen-thawed (F-T) human embryos was carried out after moderate ovarian stimulation with human menopausal gonadotrophin (HMG). Embryos were replaced 3 days after the spontaneous luteinizing hormone (LH) surge or 4 days if ovulation was induced by human chorionic gonadotrophin (HCG). Embryos were thawed a few hours prior to transfer. One-hundred-and-twenty-three transfers were effective and 23 pregnancies were achieved. The rate of ongoing pregnancies per transfer was 17.9% (22/123). The survival rate of embryos originating from cycles stimulated by a combination of an LHRH analogue and HMG in a long protocol (LA-HMG protocol) was significantly lower when compared with the rate of embryos retrieved from clomiphene citrate-HMG (CC-HMG protocol) stimulated cycles (52 versus 67%, P less than 0.05). When fresh embryos originated from cycles stimulated with an LHRH analogue and HMG in a short protocol (SA-HMG protocol), the survival rate was not affected (59 versus 67%, NS). Although the difference was not significant, the ongoing pregnancy rate per transfer according to the three protocols from which the embryos originated seemed to be better with the SA-HMG protocol: 16% with the CC-HMG protocol, 14.5% with the LA-HMG protocol versus 27.6% with the SA-HMG protocol. The success rate was independent of the number of F-T transferred embryos if at least one embryo with 100% intact blastomeres was replaced. PMID- 2108986 TI - Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist. AB - Nine obese and ten non-obese women with polycystic ovarian disease (PCO), and seven obese and eight non-obese normal women, had an oral glucose tolerance test (OGTT) before and after treatment with GnRH agonist (buserelin 400 micrograms/day s.c. for 8 weeks) in order to investigate the effect of ovarian suppression on their insulinaemic secretion. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), androstenedione (A), testosterone (T), DHEAS, cortisol and insulin (I) were measured at time 0 of OGTT; in all samples of OGTT, E2, T, A and I were also assayed. PCO patients showed higher basal androgen levels than control patients. All subjects showed a normal glycaemic response to OGTT. The mean fasting and areas under the curve (ISA) of plasma I were significantly greater in the obese PCO women than in non-obese PCO, the normal obese and non-obese women. All PCO patients showed significantly higher fasting I and ISA values in respect to all control patients. Hyperinsulinaemic responses were 89% in PCO obese, 30% in non-obese PCO and 29% in obese control patients. After buserelin treatment, these values did not change significantly in respect to pretreatment in all groups, in spite of a significant decrease of androgen secretion. During OGTT, no variations of steroid plasma concentrations were seen in both normal or hyperinsulinaemic PCO patients. The data of this study show that hyperandrogenism, hyperinsulinism and obesity were associated with different modalities in PCO patients and that a marked decrease of androgen secretion did not restore a normal insulinaemic response to OGTT, suggesting that hyperandrogenism does not produce hyperinsulinism. PMID- 2108987 TI - Anti-oestrogenic effect of clomiphene citrate in oestrogen-treated, hypogonadal women. AB - The effect of clomiphene on the pituitary response to exogenous LHRH was investigated in five hypogonadal women during long-term treatment with varying doses of oestrogen. In three of them, basal LH levels were low (less than 10 mIU/ml) and increased significantly after 8 days of treatment with clomiphene (100 mg/day). Clomiphene augmented the LH and FSH response to LHRH (an acute i.v. injection of 100 micrograms) and changed the pattern of response into that seen in the absence of the influence of ovarian steroids. We conclude that clomiphene exerts anti-oestrogenic effects on basal and LHRH-stimulated release of gonadotrophins in hypogonadal women during long-term treatment with oestrogen. PMID- 2108988 TI - The importance of follicle-stimulating hormone increase for folliculogenesis. AB - To study the role of the increase in follicle-stimulating hormone (FSH) during the early follicular phase of the menstrual cycle in folliculogenesis, eight normally cycling women were investigated in a spontaneous cycle (n = 8), a cycle treated with clomiphene citrate (n = 8), a cycle treated with FSH (n = 8) and a cycle treated with FSH plus pulsatile luteinizing-hormone-releasing hormone (LHRH) (n = 5). In the FSH and the FSH plus LHRH cycles, the leading follicle reached the size of 18 mm 2 days earlier on average than in the clomiphene treated cycles. However, the rate of growth of the leading follicle was similar in the stimulated and the spontaneous cycles. At the same time, circulating levels of FSH differed greatly among the different groups of cycles. During the early follicular phase, serum FSH levels were significantly higher in the FSH plus LHRH and the FSH cycles than in the clomiphene and the spontaneous cycles. We conclude that the preovulatory stage of the dominant follicle is advanced by high FSH levels in the early follicular phase of the cycle. It is suggested that FSH controls follicle development in women at the recruitment--selection stage. PMID- 2108989 TI - Short-term use of buserelin in combination with human menopausal gonadotrophins for ovarian stimulation for in-vitro fertilization in endocrinologically normal women. AB - Ten endocrinologically normal women were injected subcutaneously with 500 micrograms D-Ser(TBU)6-EA10-LHRH (buserelin) on days 3,4 and 5 after the start of the menses. Two types of response were observed. Five women (group A) responded promptly and had a mean number of 13.4 oocytes retreived after 11.4 days of stimulation. In the second group (B), two to three times more HMG was needed to obtain a mean number of 7.3 oocytes after 17.2 days of stimulation. The response upon stimulation could be predicted by the serum gonadotrophin output on days 4 and 5 of the cycle. One woman from group B had a premature LH rise on day 16 and luteinization; her cycle was abandoned. In the four other patients of group B, serum and urinary LH concentrations showed that pituitary gonadotrophin secretion had recovered before the ovulatory stimulus, without signs of premature luteinization. Two women in each group became pregnant, one of whom aborted. This short-term GnRH agonist treatment could be an alternative method for ovarian stimulation, although it did not totally prevent the occurrence of an endogenous LH surge. PMID- 2108990 TI - The effect of HCG supplementation after combined GnRH agonist/HMG treatment in an IVF programme. AB - The necessity of luteal-phase supplementation in an IVF programme is of continuing interest. After ovarian stimulation with clomiphene and human menopausal gonadotrophin (HMG), the beneficial effect of supporting the luteal phase has never been scientifically demonstrated. After ovarian stimulation with GnRH agonist/HMG, the luteal phase seems to be inadequate, but in a previous study we did not find evidence to support the need for oral progesterone supplementation. To evaluate the beneficial effect of human chorionic gonadotrophin (HCG) supplementation, we performed a multicentre, double-blind, randomized study with HCG (193 transfers) against placebo (194 transfers). The ongoing pregnancy rate per transfer cycle was significantly better with HCG (18.7 versus 9.3). This is the first truly objective (randomized) study demonstrating the beneficial effect of supporting the luteal phase in an IVF programme. PMID- 2108991 TI - Sialidase (neuraminidase) activity among gram-negative anaerobic and capnophilic bacteria. AB - A filter paper spot test with 2'-(4-methylumbelliferyl)-alpha-D-N acetylneuraminic acid as a substrate was used to study the prevalence of sialidase activity among gram-negative anaerobic and capnophilic bacteria. A total of 567 isolates representing four genera of obligate anaerobes and four genera of capnophilic organisms was tested. Sialidase activity was detected in 94% of 66 isolates from the Bacteroides fragilis group, 98% of 66 B. bivius isolates, and all isolates of the following species (number of isolates follows species name): B. capillosus, 4; B. levii, 2; B. denticola, 22; B. loescheii, 23; B. melaninogenicus, 32; B. forsythus, 44; and B. buccalis, 2. However, sialidase activity was detected in only 29% of 7 B. buccae isolates, 79% of 14 B. disiens isolates, and 55% of 11 B. oralis isolates. Sialidase activity was not detected among any of 13 isolates of B. gracilis, 12 isolates of B. ureolyticus, 61 isolates of B. intermedius, or 26 isolates of B. corporis. Porphyromonas (Bacteroides) asaccharolytica (20 isolates) and P. endodontalis (8 isolates) did not demonstrate sialidase activity, while 25 isolates of P. gingivalis were sialidase positive. Sialidase activity was found in 10 (100%) of 10 isolates of Capnocytophaga ochracea of C. sputigena but not in any of 4 C. gingivalis isolates. Other gram-negative anaerobic or capnophilic bacteria, including the following, were negative for sialidase activity: Fusobacterium nucleatum, 39 isolates; Wolinella recta, 19 isolates; Eikenella corrodens, 17 isolates; Haemophilus aphrophilus, 10 isolates; and Actinobacillus actinomycetemcomitans, 10 isolates. These data demonstrate sialidase activity in several species of the genera Bacteroides and Porphyromonas and suggest that this characteristic may be useful for identification. PMID- 2108992 TI - Species identities of enterococci isolated from clinical specimens. AB - Conventional tests and commercially available systems were used to determine the species identities of clinical isolates of enterococci. Strict adherence to the conventional test scheme of Facklam and Collins (R. R. Facklam and M. D. Collins, J. Clin. Microbiol. 27:731-734, 1989) resulted in the misidentification of lactose-negative Enterococcus faecalis isolates as Enterococcus solitarius, but this problem was overcome by the application of additional tests. The commercially available systems tested were unable to recognize some of the more recently described enterococcal species. E. faecalis accounted for 87.1% of 302 consecutive isolates. Enterococcus faecium (8.6%), Enterococcus avium (0.7%), Enterococcus durans (0.3%), Enterococcus gallinarum (1.0%), Enterococcus casseliflavus (1.0%), Enterococcus hirae (0.3%), and Enterococcus raffinosus (0.3%) isolates were also identified. None of the isolates produced beta lactamase, but 15.4% of 235 isolates tested, including 1 strain of E. gallinarum, displayed high-level resistance to gentamicin. PMID- 2108993 TI - Recovery of vancomycin-resistant gram-positive cocci from children. AB - A cross-sectional survey of vancomycin-resistant gram-positive cocci (VRGPC) in the feces of children was initiated after several bacteremic infections with these organisms occurred at our hospital. A selective medium consisting of colistin-nalidixic acid agar, 5% sheep blood, vancomycin (5 mg/liter), and amphotericin B (8 mg/liter) was developed to isolate VRGPC. A single stool specimen submitted to the clinical microbiology laboratory from each of 48 patients was inoculated onto the medium. Plates were incubated at 35 degrees C with 5% carbon dioxide and examined at 24, 48, and 72 h. Susceptibilities were determined by broth microdilution. A total of 14 isolates from 11 of 48 (22%) children were recovered. The density of growth ranged from a single colony to 2+. The VRGPC were identified as Leuconostoc lactis (n = 2), Lactobacillus confusus (n = 4), Enterococcus species (n = 5), and Lactococcus lactis (n = 3). One strain of Lactobacillus confusus was recovered from both the stool and the blood of one of these patients. The MICs of vancomycin were 4 micrograms/ml for one of the isolates, 8 micrograms/ml for four of the isolates, and more than 16 micrograms/ml for the remaining eight isolates. All isolates were susceptible to both penicillin and ampicillin. Only 1 of the 11 children had received prior treatment with vancomycin. We conclude that low concentrations of VRGPC may be common in the gastrointestinal tracts of children. PMID- 2108994 TI - Sequence analysis and amplification by polymerase chain reaction of a cloned DNA fragment for identification of Mycobacterium tuberculosis. AB - Analysis of the 1,016-base-pair sequence of a putative probe for identification of Mycobacterium tuberculosis revealed two almost identical fragments of 507 and 509 bases. From this sequence two pairs of primers were synthesized (MtbAB and MtbCD), ranging from 18 to 22 nucleotides, for use in polymerase chain reactions (PCRs) with DNA from six reference strains of M. tuberculosis, as well as type strains of M. bovis, M. bovis BCG, M. kansasii, M. avium, M. intracellulare, and M. scrofulaceum. Although there was amplification of DNA from all mycobacterial strains included in the study, when used as probes, a predominant band, fragment CD from M. tuberculosis H37Rv DNA, proved to be more specific for strains of M. tuberculosis than the original probe, pMTb4, was. Amplified fragments from as little as 1 fg of DNA (equivalent to one-fifth of an organism) could be resolved on ethidium bromide-stained gels loaded with a 1/10 volume of PCR. Furthermore, it was possible to amplify specific DNA sequences from frozen M. tuberculosis H37Rv organisms which were thawed prior to PCR. PMID- 2108995 TI - Detection of murine typhus infection in fleas by using the polymerase chain reaction. AB - Polymerase chain reaction (PCR) amplification of DNA was used to detect the etiologic agent of murine typhus, Rickettsia typhi, in experimentally infected adult fleas. A primer pair derived from the 17-kilodalton antigen sequence of typhus and spotted fever group rickettsiae was used to amplify a 434-base-pair (bp) fragment of the genome of the murine typhus rickettsiae. The amplified 17 kilodalton protein antigen-specific sequence was detected in ethidium bromide stained agarose gels in individual fleas as early as 2 days after exposure to rickettsemic rats (two of six tested). The 434-bp sequence was not detected in uninfected control fleas. A dot hybridization assay used to detect the 434-bp fragment was also specific and about 100-fold more sensitive than the agarose gel PCR assay. Since the PCR assay employed a boiled extract of triturated fleas, both PCR and an antigen capture enzyme-linked immunosorbent assay (ELISA) could be performed on the same individual flea homogenate. The ELISA identified 12 infected fleas out of 29 randomly selected fleas, compared with 14 specimens which were positive by PCR. The PCR assay detected rickettsiae in samples in which no viable rickettsiae were detected by plaque assay. Like the ELISA, the PCR assay sensitivity was due in part to its suitability for detecting small numbers of both live and dead R. typhi in fleas. PMID- 2108997 TI - Interpretive criteria for disk diffusion susceptibility testing of mupirocin, a topical antibiotic. AB - Five hundred gram-positive clinical bacterial isolates were tested for susceptibility to mupirocin by broth microdilution and disk diffusion methods (5- and 10-micrograms disks). All but 1 of 330 staphylococci (including 100 oxacillin resistant Staphylococcus aureus) were susceptible to less than or equal to 1.0 micrograms of mupirocin per ml. With a susceptible MIC breakpoint of less than or equal to 2.0 micrograms/ml, the corresponding zone diameter breakpoints were greater than or equal to 14 mm for 5-micrograms disks and greater than or equal to 16 mm for 10-micrograms disks. With either disk potency, susceptible staphylococci were effectively separated from more resistant gram-positive species such as the enterococci and gram-positive bacilli. PMID- 2108996 TI - Immunologic characterization of a 35-kilodalton recombinant antigen of Mycobacterium tuberculosis. AB - A 35-kilodalton (kDa) recombinant antigen (35-kDa antigen) produced by Escherichia coli JM107 carrying DNA from Mycobacterium tuberculosis was purified and immunologically examined by in vivo and in vitro methods. A monoclonal antibody (2B2) was produced against the 35-kDa antigen. The protein was purified from the insoluble fraction of the recombinant E. coli strain by either affinity chromatography with the 2B2 monoclonal antibody or preparative isoelectric focusing. In enzyme-linked immunosorbent assay and Western blot (immunoblot) analyses, antibody to 2B2 reacted with whole-cell sonic extracts of M. tuberculosis and other slowly growing mycobacteria but not with two rapid growers, M. chelonae and M. fortuitum. An injection series totaling less than 1 mg of purified protein without adjuvant elicited a humoral response in guinea pigs. In one guinea pig, 10 micrograms of purified protein injected intradermally elicited both a humoral and a cell-mediated response. Results of these studies suggest that the 35-kDa antigen is a membrane-associated protein that stimulates both humoral and cell-mediated immune responses and should be evaluated as a vaccine candidate. PMID- 2108998 TI - Two confirmatory tests for identification of Neisseria gonorrhoeae from primary culture. AB - We compared a fluorescent monoclonal antibody and a DNA probe for identification of Neisseria gonorrhoeae (GC) from primary genital cultures of presumptive GC and selected bacterial isolates other than GC. The monoclonal antibody was sensitive (94%) and specific (100%) enough to identify GC in selective primary genital culture. The DNA probe was sensitive (95%) but not adequately specific (65%) to function as a confirmatory test. PMID- 2109000 TI - Mutans streptococci in plaque from margins of amalgam, composite, and glass ionomer restorations. AB - Levels of mutans streptococci in plaque samples from margins of Class II amalgam (Dispersalloy), composite (P-10), and glass-ionomer (Ketac Silver) restorations were compared. Fifty-one children, each having one of the restorations in a permanent first molar, were part of an inter-individual comparison, giving 17 restorations of each material. The age of the children, the age of the restorations, and the salivary levels of mutans streptococci were comparable in the three groups. Another seven children--each having both a composite and a glass-ionomer restoration of the same age placed on contralateral premolar or molar teeth--were part of an intra-individual comparison. The percentage mutans streptococci of total CFU count in plaque was higher on composite (mean 13.7) and amalgam (mean 4.3) than on glass-ionomer (mean 1.1) restorations in the inter individual comparison, and higher on composite (mean 4.2) than on glass-ionomer (mean 0.4) restorations in the intra-individual comparison. In both comparisons, the differences in values between samples from glass-ionomer restorations and samples from composite or amalgam restorations were statistically significant (p less than 0.05). PMID- 2108999 TI - Experimental infection of calves with an apparently specific goat-pathogenic strain of Mycobacterium paratuberculosis. AB - Four calves and four goat kids were inoculated perorally with a Norwegian goat pathogenic strain of Mycobacterium paratuberculosis. None of the calves developed clinical disease, pathological lesions or humoral antibody response, but the organism was reisolated from the small intestine and mesenteric lymph nodes when the calves were slaughtered after 7, 12, 14 and 18 months, respectively. As one of the goats died of non-specific causes and one did not become infected, two remained as positive controls. One of these became subclinically and one clinically infected, but both showed distinct histopathological lesions at necropsy. Both were shown to be positive in the complement fixation test (CFT) and the enzyme-linked immunosorbent assay (ELISA) but only the clinically affected goat proved positive in the agar gel immunodiffusion (AGID) test. The AGID test was found to be of low diagnostic value, and the ELISA was as sensitive as the CFT in detecting infection at an early stage. However, when infection was finally established, the ELISA titres became far higher than the CFT titres. The results confirm previous experience in Norway, that the current Norwegian strain of M. paratuberculosis has little or no pathogenicity for cattle. PMID- 2109001 TI - In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse. AB - The purpose of this work was to assess the in vitro antiviral effectiveness of a mouthrinse (Peridex) containing 0.12% chlorhexidine gluconate (CH) on several viruses that are associated with the oral cavity. These included herpes simplex virus (HSV), cytomegalovirus (CMV), influenza A, parainfluenza, polio, and hepatitis B (HBV). Virucidal assays in tissue cultures were performed on all viruses except HBV. The virucidal effect on HBV was assessed by inactivation of the DNA polymerase contained within the Dane particle of HBV. The CH mouthrinse had virucidal activity against all of the viruses, except polio, in as little as 30 s. The virucidal activity increased with time. However, there were differences in the responses of these viruses to the challenge of the CH mouthrinse, probably due to subtle differences in the physical/chemical structures of the virus envelopes. Results on DNA polymerase of the HBV virus were similar to those on the other viruses, except polio, suggesting a common mechanism. With respect to this mechanism, it was proposed that CH exerted its antiviral effect on the envelopes of these viruses, and that the absence of an envelope on polio precluded effectiveness against this virus. PMID- 2109002 TI - Effects of prostacyclin on bronchoconstriction and neutropenia induced by inhaled platelet-activating factor in man. AB - We studied the effects of prostacyclin (PGI2) on the airway responses to platelet activating factor (PAF) in a randomized and crossover study in eight normal subjects. PGI2 or diluent (glycine buffer) was continuously infused on 2 separate days. Two breaths of PAF (21 micrograms) were inhaled three times every 15 minutes and airflow at 30% of vital capacity from partial flow-volume curves (Vp30) was measured. PGI2 (4 ng/kg/min) had no effect on Vp30 or blood pressure, whereas heart rate increased from 70.3 +/- 3.9 to 73.7 +/- 4.0 beats/min (mean +/ SEM; p less than 0.01). Two subjects did not complete the study because of transient hypotension. PGI2 had no effect on PAF-induced bronchoconstriction with maximal decreases in Vp30 of 42.0 +/- 8.0% (p less than 0.01) during PGI2 and 49.8 +/- 14.2% (p less than 0.02) during diluent infusion. Ex vivo platelet aggregation to PAF (10(-9) to 10(-7) mol/L) was significantly inhibited by PGI2. Circulating neutrophils decreased from 4.7 +/- 0.9 x 10(9)/L to 1.5 +/- 0.3 x 10(9)/L (p less than 0.05) 5 minutes after the first PAF inhalation during diluent infusion, whereas there was no significant change with PGI2. Thus, PGI2 does not influence PAF-induced bronchoconstriction in man despite causing marked inhibition of ex vivo PAF-induced platelet aggregation and preventing the fall of neutrophils. PMID- 2109003 TI - Small-area analysis of gastrointestinal disease hospital discharge variation: are the poor at risk? AB - Capitation plans may place their enrollees at risk of rationed services if they do not adjust for underlying patient characteristics that dictate differing levels of care. To assess the degree to which population-based socioeconomic characteristics are associated with hospital use, this study explored small-area variation in hospital discharges for gastrointestinal and liver (GI) Diagnosis Related Groups (DRGs). Utilizing a 1980 Michigan database of 1.5 million discharges, we constructed age-adjusted, population-based discharge rates for the GI DRGs. We then evaluated the effect of poverty, defined by the percent of households in a hospital market community below the poverty line. Using regression techniques, we found that poverty explained 27.5% of the variation in GI hospital discharges, with the poor admitted more often (p less than 0.0001). Using cost weighted discharge rates as the dependent variable, we found that poverty explained 20.3% (p = 0.0003) of the variation in cost weighted discharges. These results suggest that poverty explains a significant amount of variation in hospital discharges and has a significant effect on associated small area hospitalization costs in GI diseases. Practicing gastroenterologists and surgeons need to be aware of factors that influence patients utilizing their services in order to retain their role as patient advocates as changes in payment systems are suggested. PMID- 2109005 TI - Motor pattern of the sphincter of Oddi in patients with juxtapapillary diverticula. AB - In 15 patients with duodenal diverticula close to the papilla of Vater we evaluated the motor activity of the sphincter of Oddi by endoscopic biliary manometry. Both basal pressure and phasic activity were similar to those in nine patients without biliopancreatic disease and in 60 patients with common bile duct stones. The anatomical relationship between the papilla and diverticula did not lead to any change in the motor pattern. If juxtapapillary diverticula are associated with a higher prevalence of biliopancreatic disease, dysfunction of the sphincter of Oddi does not seem to play a pathogenic role. PMID- 2109004 TI - Treatment of ulcerative colitis with fish oil n--3-omega-fatty acid: an open trial. AB - We evaluated the efficacy of fish oil n--3-omega-fatty acids, inhibitors of leukotriene synthesis, in the treatment of ulcerative colitis. An open trial of 10 patients with mild to moderate ulcerative colitis who had either failed (n = 9) or refused (n = 1) conventional therapy was performed. Patients received 15 MAX-EPA capsules containing a total of 2.7 g of eicosapentanoic acid in three divided doses daily for 8 weeks. The activity of ulcerative colitis and response to therapy was based upon daily stool diaries, sigmoidoscopy, and symptomatic response. All patients tolerated the fish oil and showed no alteration in routine blood studies. Seven patients had moderate to marked improvement; steroid dose could be reduced in four of the five patients on prednisone. Three patients had little or no improvement. No patient worsened. These results of our open study appear to justify a double-blind trial of this dietary supplement in ambulatory patients with ulcerative colitis. PMID- 2109006 TI - Acute pancreatitis associated with non-A-non-B hepatitis. Report of a case. AB - A 33-year-old man, vaccinated against hepatitis B virus, working in an hemodialysis unit, pricked himself with a needle used in a patient. Four weeks later he developed acute hepatitis along with acute pancreatitis. The pancreatitis resolved, but the liver disease ran a chronic course. The diagnosis of hepatitis non-A-non-B (NANB) was made on the following criteria: (a) epidemiologic circumstances, (b) exclusion of other causes of acute and/or chronic liver disease, (c) chronic indolent course, and (d) compatible histological features. The diagnosis of acute pancreatitis was made with clinical, biological, and radiological data. We believe that the pancreatitis was related to the NANB viral infection, as they began simultaneously and other causes of pancreatitis were eliminated. Such an association has been reported mainly with hepatitis B and exceptionally with hepatitis A. It has also been observed in the course of fulminant NANB viral hepatitis, but we believe this to be the first case associated with a benign form of NANB. PMID- 2109007 TI - Hypoventilation during endoscopy: a questionable cause for arterial desaturation. PMID- 2109008 TI - Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. AB - Astrocytes have the capacity to secrete or respond to a variety of cytokines including IL-1, IL-6, IL-3, and TNF-alpha. In this study, we have examined the capacity of astrocytes to secrete TNF-alpha in response to a variety of biologic stimuli, particularly cytokines such as IL-1 and IFN-gamma, which are known to be present in the central nervous system during neurologic diseases associated with inflammation. Rat astrocytes do not constitutively produce TNF-alpha, but have the ability to secrete TNF-alpha in response to LPS, and can be primed by IFN gamma to respond to a suboptimal dose of LPS. IFN-gamma and IL-1 beta alone do not induce TNF-alpha production, however, the combined treatment of IFN-gamma and IL-1 beta results in a striking synergistic effect on astrocyte TNF-alpha production. Astrocyte TNF-alpha protein production induced by a combined treatment of either IFN-gamma/LPS or IFN-gamma/IL-1 beta occurs in a dose- and time-dependent manner, and appears to require a "priming signal" initiated by IFN gamma, which then renders the astrocyte responsive to either a suboptimal dose of LPS or IL-1 beta. Astrocyte TNF-alpha production by IFN-gamma/LPS stimulation can be inhibited by the addition of anti-rat IFN-gamma antibody, whereas IFN-gamma/IL 1-induced TNF-alpha production is inhibited by antibody to either IFN-gamma or IL 1 beta. Polyclonal antisera reactive with mouse macrophage-derived TNF-alpha neutralized the cytotoxicity of IFN-gamma/LPS and IFN-gamma/IL-1 beta-induced astrocyte TNF-alpha, demonstrating similarities between these two sources of TNF alpha. We propose that astrocyte-produced TNF-alpha may have a pivotal role in augmenting intracerebral immune responses and inflammatory demyelination due to its diverse functional effects on glial cells such as oligodendrocytes and astrocytes themselves. PMID- 2109009 TI - VH and VL gene usage by murine IgG antibodies that bind autologous insulin. AB - To assess the recognition structures of antibodies that bind a self-Ag, we used mRNA analysis to identify the V region genes of IgG antibodies that bind autologous insulin. Four anti-insulin mAb from primary immunization of BALB/c mice use different combinations of H and L chain V region genes. Two VH genes are from the V-gam 3-2 and V-gam 3-8 families that are infrequently expressed in adult BALB/c mice, and two VH genes are members of the J558 family. Each anti insulin antibody uses a different Vk gene family. Two antibodies express common Vk genes (Ox1 and Vk21C), whereas two other Vk genes are unusual in BALB/c mice. One Vk gene may represent a BALB/c equivalent of the VkOx2 subfamily and another is identical to a Vk used by anti-idiotypic antibodies from C57Bl/6 mice. When compared with known germ-line counterparts, all of the Vk sequences are close to germ-line configuration. In contrast, the germ-line counterparts for the anti insulin VH genes are not known, however, they differ only in five to seven predicted amino acids from VH of other expressed antibodies. One antibody (mAb 123) differs in one amino acid in complementarity-determining regions 1 and 2 from the VH of the murine tumor BCL1, and another (mAb 126) employs an unmutated DFL16.1 germ-line D segment. These data suggest that antibodies binding autologous insulin use V gene components that are not extensively mutated, even when derived by immunization with heterologous insulin. PMID- 2109010 TI - Phorbol myristate acetate-induced down-modulation of CD4 is dependent on calmodulin and intracellular calcium. AB - PMA causes rapid down-modulation of CD4 molecules on murine immature thymocytes, human PBL, and CD4-positive human tumor cell lines, but not on murine peripheral lymphocytes. The mechanisms of phorbol ester-induced down modulation of CD4 molecules, however, have not been elucidated. To determine how PMA down-modulates CD4 expression by T lymphocytes, we studied the ability of inhibitors of protein kinase C, calmodulin, actin, and tubulin to block PMA-induced modulation of CD4 in several murine and human cell types. We also tested the ability of intracellular and extracellular calcium chelators to block CD4 internalization. There was marked variability in the degree of PMA-induced down-modulation of CD4 among various cell types. The effects of PMA on CD4 expression were greater for murine thymocytes, for human PBL, and for the human lymphoblastic leukemia cell line, MOLT-3, than for any of the other cell types studied. The protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, blocked phosphorylation but not internalization of CD4 molecules induced by PMA. Therefore, phosphorylation of CD4 molecules by protein kinase C is not required for the internalization of the molecules. Internalization was blocked by both inhibitors of calmodulin, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide, and trifluoperazine. PMA-induced internalization of CD4 was blocked by Quin-2 AM, which chelates intracellular calcium. EGTA, which chelates extracellular calcium, did not block internalization. Inhibitors of actin or tubulin did not block internalization. These results suggest that PMA-induced modulation of CD4 can occur in the absence of phosphorylation of the CD4 molecules and is calmodulin and intracellular calcium dependent. PMID- 2109012 TI - IFN-gamma production in tissues of mice during acute infection with lymphocytic choriomeningitis virus. AB - As shown by a single-cell solid-phase ELISA, splenocytes as well as liver lymphoid cells from unmanipulated specific-pathogen free mice synthesized and released IFN-gamma. Synthesis of this lymphokine could not be demonstrated either on the transcriptional level by Northern blotting or immunocytochemically. Thus, IFN-gamma is constitutively produced in mice, although in low quantities. During acute infection with lymphocytic choriomeningitis virus, IFN-gamma mRNA became detectable in spleen and brain but not in the liver. In spleens and livers of these mice, the numbers of cells synthesizing the lymphokine were increased and many were seen in foot tissue undergoing a delayed-type hypersensitivity reaction after intraplantar inoculation of the virus. In contrast, few IFN-gamma-producing cells were found in the inflammatory infiltrates of leptomeninges and choroid plexus after intracerebral infection. PMID- 2109011 TI - Murine eosinophils and IL-1: alpha IL-1 mRNA detection by in situ hybridization. Production and release of IL-1 from peritoneal eosinophils. AB - The presence of IL-1 mRNA in eosinophils from mice infected with larvae of the parasite Mesocestoides corti was investigated by in situ hybridization technique. S35 labeled cDNA probe for alpha IL-1, hybridized with mRNA in murine eosinophils and macrophages. After 6 h of LPS stimulation eosinophils were able to express mRNA in their cytoplasm. This expression was highly increased by the addition of indomethacine. The IL-1 mRNA expression in murine macrophages was higher than in eosinophils in LPS-stimulated cells. This difference was statistically significant, p less than 0.001. To test if eosinophils may produce and release IL 1 in the culture medium, we isolated these cells in a Percoll gradient. Cell preparations with a purity exceeding 94% were cultured with various stimuli and their supernatants were tested for IL-1 activity. Eosinophils produced 169.65 +/- 73 U/ml when stimulated with LPS (n = 14). A dose-dependent response was obtained when the eosinophils were in the presence of the calcium ionophore A23187. Controls were performed to rule out the contribution of the contaminating population on the thymocyte proliferating activity. They were also used to detect other possible causes of interference in the assay, such as leukotrienes or TNF. IL-1 in supernatants was also detected using a conversion assay such as EL-4 thymoma cells. IL-1 activity was first detected in culture supernatants 18 h later, maximal production being in the first 24 h. In accordance with our hybridization results, an increase in IL-1 activity was obtained when eosinophils were stimulated with LPS and treated with indomethacine. The factor had a molecular mass between 16 to 20 kDa that corresponded to the described for murine IL-1. Inasmuch as IL-1 is an important mediator of inflammatory reactions this IL may enhance the proinflammatory action of eosinophils. PMID- 2109013 TI - Hepatic immune complex elimination studied with FITC-labelled antigen. AB - Fluorescein isothiocyanate (FITC)-labelled model antigens (Ags) were used to form soluble IgG immune complexes (ICs) in vitro. The Ag and IC preparations were found to be excellent alternatives to isotope-tagged preparations for the study of plasma clearance after intravenous injection in rats. Ag and IC were eliminated from the blood at the same rate. By direct fluorescence microscopy the FITC-labelled IgG ICs could easily be detected in hepatic non-parenchymal liver cells 30 min after intravenous injection, whereas uncomplexed Ag was apparently taken up by the liver to a much lesser extent. PMID- 2109014 TI - Modification of the clonogenic assay for the detection of lymphokine activated killer cell activity. AB - The soft agar clonogenic assay using [3H]thymidine uptake as an endpoint was adapted for the detection of human LAK activity against the Daudi lymphoma cell line and human tumor cells obtained by biopsy. Using Daudi cells as the target population the modified agar assay was more sensitive than the conventional 4 h 51Cr release assay. Use of a single layer agar assay allowed the assessment of LAK cytotoxic/cytostatic activity against Daudi lymphoma cells after cell to cell contact, while a two layer system permitted evaluation of the role of soluble mediators in LAK/target cell interactions. This study shows that LAK cells can either kill or inhibit the proliferation of Daudi cells by two mechanisms: one which requires cell-to-cell contact, and a second via soluble mediators. As determined by the use of neutralizing antisera, the soluble factor(s) are not tumor necrosis factor and interferon-gamma. Of the nine individual human tumor samples obtained by biopsy. 89% were sensitive to allogeneic LAK cells when the two populations were admixed. Of these nine tumors 44% were inhibited by LAK derived soluble factors. The soft agar assay system should serve as a useful tool for determining the sensitivity of human tumors to LAK cells and for studying the mechanisms of LAK anti-tumor activity. PMID- 2109015 TI - Parasite antigens expressed in Escherichia coli. A refined approach for epidemiological analysis. AB - A simple method is described to generate carrier-free recombinant antigens following their expression in Escherichia coli. A plasmid, called pMSgt11, has been constructed such that the cleavage site for the protease factor Xa separates the recombinant antigen from an enzymatically active beta-galactosidase. Thus, rapid purification of the active beta-galactosidase recombinant protein, followed by digestion with factor Xa, releases the antigen of interest. The pMSgt11 plasmid is compatible with the phage expression vector, lambda gt11 and the feasibility of applying this system has been demonstrated using malarial recombinant antigens. Inserts from lambda gt11 recombinant Plasmodium falciparum clones have been recloned into the EcoRI site of pMSgt11 and the expressed soluble fusion proteins have been purified from crude extracts using a one step affinity chromatography. After protease digestion, the fusion protein cleavage products were analysed by immunoblot with a panel of different human immune sera. We were able to successfully demonstrate specific antibody titers to the parasite derived carrier-free antigen, without interference from anti-Escherichia coli specific antibodies. The general application of this approach to epidemiological analysis is discussed. PMID- 2109017 TI - Patients with erosive lichen planus may have antibodies directed to a nuclear antigen of epithelial cells: a study on the antigen nature. AB - Two patients with erosive lichen planus and latent HBV infection who had circulating antibodies directed to nuclei of epithelial cells are described. The nature of such antigen has been investigated by indirect immunofluorescence, double immunodiffusion, counterimmunoelectrophoresis, enzyme-linked immunosorbent assay, enzyme treatments, and immunoblotting. The antigen cannot be identified as RNP, histone, soluble nuclear protein, nDNA, or ssDNA. It may be a DNA protein complex and preliminary immunoblotting data support the thesis that it may be a multimolecular complex. PMID- 2109016 TI - An enzyme-linked immunosorbent assay for the determination of human IgG subclass antibodies directed against Branhamella catarrhalis. AB - An ELISA procedure to determine the distribution of human IgG subclass antibodies directed against the gram-negative bacterium Branhamella catarrhalis has been developed using commercially available monoclonal anti-IgG subclass antibodies. Using whole bacteria as coating antigen the specificity of the assay was determined and showed minimal cross-reactivity with a range of other bacteria. Estimations of IgG1, IgG2, IgG3, IgG4 and total IgG antibodies directed against this antigen were performed. All normal adult sera tested had measurable antibody levels of specific IgG1, IgG2, IgG3 and total IgG. Specific IgG4 was undetectable in the majority of adult sera. These assays will be of value for investigation of both children and adults with suspected immunodeficiency and recurrent upper respiratory tract infection. PMID- 2109018 TI - Polyamine-dependent post-translational modification of proteins in differentiating mouse epidermal cells. AB - In order to get a better understanding of the role played by polyamines in calcium-induced epidermal cell differentiation, the time course of their metabolism was investigated. Results demonstrate that differentiating epidermal cells are characterized by time-dependent changes in polyamine concentrations. An early polyamine catabolic phase, characterized by increased total putrescine concentration and drastic reduction of both spermidine and spermine levels, is followed by active spermidine biosynthesis. The differences in putrescine and, in particular, spermidine metabolism are reflected in a time-dependent modulation of protein-bound polyamine derivatives. In fact, upon addition of calcium to the culture medium, hypusine N epsilon-(4-amino-2-hydroxybutyllysine) is rapidly reduced to undetectable levels. The very low hypusine level is paralleled by an increase in gamma-glutamyl putrescine derivatives and followed by a large increase in gamma-glutamyl spermidine derivatives; in addition, there is a remarkable concomitant biosynthesis of transglutaminase-catalyzed mono and bis gamma-glutamyl spermidine derivatives and epsilon(gamma-glutamyl)lysine cross links. The effect of TPA and RA on hypusine formation is also reported. PMID- 2109019 TI - Heat-shock protein in Mycoplasma pneumoniae shown by immunoblotting to be related to the bacterial common antigen. PMID- 2109020 TI - Kappa and lambda light chain composition of antibody to the capsular polysaccharide of Haemophilus influenzae type b. AB - Concentrations of total immunoglobulins bearing kappa and lambda light chains were measured in the sera of 215 healthy white children aged 6 months to 10 years. Both kappa and lambda concentrations increased with age. However, the concentration of immunoglobulins bearing kappa light chains increased at a greater rate than those bearing lambda light chains (P = .01). Thus, the kappa:lambda ratio of the youngest children (6-24 months) was significantly lower than that of the oldest (25-130 months) (P = .0015). The relationship between the IgG antibody concentration and the light chain composition of the specific antibody directed to Haemophilus influenzae type b (Hib) polysaccharide was also assessed in 62 of 215 serum samples with detectable Hib antibody. The IgG Hib antibody concentration was strongly correlated with the kappa:lambda Hib antibody ratio (r = .60, P = .001), and this correlation was independent of age. Thus, light chain selection and response to polysaccharides may be regulated by common mechanisms that mature late in ontogeny. PMID- 2109021 TI - Prophylaxis against Neisseria meningitidis infections and antibody responses in patients with deficiency of the sixth component of complement. AB - Forty South African patients with homozygous deficiency of the sixth component of complement (C6) have been identified in an area where group B meningococcal meningitis is endemic; 22 of the 24 proband cases presented with recurrent meningococcal meningitis. In a 2- to 4-year prospective study, patients with recurrent infections who received monthly prophylactic long-acting penicillin were significantly protected from subsequent neisserial infection compared with those who did not receive penicillin (P = .02, Fisher's exact test). Heterogeneous susceptibility to neisserial infection was confirmed by following C6-deficient patients who presented with one or no Neisseria meningitidis infections. These patients, on no prophylaxis, had significantly fewer infections (P = .004) than did patients who presented with recurrent disease. Functional C6 activity was restored by transfusion of fresh frozen plasma in a C6-deficient patient resistant to conventional antibiotic treatment. Antibody levels to the serotype 2 outer membrane proteins were significantly elevated in C6-deficient patients compared with control groups (P = .001). PMID- 2109022 TI - Polymerase chain reaction amplification of a repetitive DNA sequence specific for Mycobacterium tuberculosis. AB - A segment of DNA repeated in the chromosome of Mycobacterium tuberculosis was sequenced and used as a target for amplification using polymerase chain reaction (PCR). The sequences of the primers (5' to 3') were CCTGCGAGCGTAGGCGTCGG and CTCGTCCAGCGCCGCTTCGG, and a temperature of 68 degrees C was used for annealing the primers in the reaction. Amplification produced a 123-base-pair fragment with an internal SalI site. The specific PCR product was obtained with input DNA from 11 different strains of M. tuberculosis and Mycobacterium bovis and one strain of Mycobacterium simiae. No product was detected with DNA from 28 strains of the Mycobacterium avium complex, Mycobacterium scrofulaceum, Mycobacterium kansasii, Mycobacterium fortuitum, Mycobacterium chelonei, and Mycobacterium gordonae. The PCR product was detected by gel electrophoresis after 30 cycles using 1 fg of input DNA. Amplification of this sequence may provide the basis for an assay to detect M. tuberculosis directly in clinical material. PMID- 2109023 TI - Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon alpha, and interferon-gamma in the serum of patients with septic shock. Swiss Dutch J5 Immunoglobulin Study Group. AB - Serum concentrations of immunoreactive tumor necrosis factor/cachectin (TNF), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), and interferon alpha (IFN alpha) were prospectively measured in 70 patients with septic shock to determine their evolution and prognostic values. In a univariate analysis, levels of TNF (P = .002) and IL-1 beta (P = .05) were associated with the patient's outcome, but not IFN alpha (P = .15) and IFN gamma (P = .26). In contrast, in a stepwise logistic regression analysis, the severity of the underlying disease (P = .01), the age of the patient (P = .02), the documentation of infection (nonbacteremic infections vs. bacteremias, P = .03), the urine output (P = .04), and the arterial pH (P = .05) contributed more significantly to prediction of patient outcome than the serum levels of TNF (P = .07). After 10 days, the median concentration of TNF was undetectable (less than 100 pg/ml) in the survivors, whereas it remained elevated (305 pg/ml, P = .002) in the nonsurvivors. Thus, in patients with septic shock due to various gram-negative bacteria, other parameters than the absolute serum concentration of immunoreactive TNF contributed significantly to the prediction of outcome. PMID- 2109024 TI - Phenotypes and mechanisms in the transformation of hematopoietic cells. AB - Interleukin 3 (IL-3) is a growth factor that supports the proliferation of early hematopoietic stem cells, as well as cells that are committed to a variety of the myeloid lineages. The mechanisms by which IL-3 functions have been studied through the use of a series of IL-3-dependent cell lines isolated from myeloid leukemias or long-term bone marrow cultures. A variety of studies have implicated tyrosine phosphorylation in IL-3 signal transduction. One of the substrates of phosphorylation is a 140 kDa, IL-3-binding protein that is speculated to be the biologically relevant IL-3 receptor. IL-3, through tyrosine phosphorylation, supports viability and growth through the regulation of transcription of a series of genes including c-myc and c-pim-1. The c-myc gene contributes to viability, in part, by regulating the transcription of the ornithine decarboxylase gene. The role of growth factors in differentiation is less clear. By studying IL-3 dependent myeloid leukemia cell lines, two genes have been identified whose altered expression is associated with blocking the ability of the cells to differentiate. The c-myb gene is a nuclear DNA binding protein that has been implicated in myeloid transformation in a number of systems. The Evi-1 gene is a novel gene of the zinc finger family of transcriptional activators. Possible mechanisms by which these genes interfere with normal differentiation are discussed. PMID- 2109025 TI - Regulation of cellular gene expression by interferon-gamma: involvement of multiple pathways. AB - Interferons (IFNs) classified as type I (IFN-alpha and -beta) and type II (IFN gamma) interact with different receptors and regulate the expression of a number of genes in common, whereas the expression of certain other genes is regulated differentially by the type I or type II IFNs. Regulation of cellular gene expression by IFN-gamma was studied with the help of two cDNA clones (called C5-4 and C13) isolated in our laboratory and cDNA clones for human leukocyte antigen (HLA) class I (HLA-B) and class II (HLA-DR alpha, -DR beta) genes. The results indicate that IFN-gamma induced the expression of the cognate genes, but in different manners. IFN-gamma induced the transcription of all four genes as determined by nuclear run-on transcription analyses, but the induction of C5-4 genes transcription was inhibited by cycloheximide and anisomycin, indicating that some newly synthesized protein, presumably induced by IFN-gamma, was required for the transcriptional activation of the C5-4 gene. On the contrary, IFN-gamma-induced transcription of HLA class I, class II and C13 genes was unaffected by cycloheximide or anisomycin. However, these inhibitors completely blocked the accumulation of the HLA class II gene transcripts, but not HLA class I or C13 gene transcripts. Results suggest that some newly synthesized protein factor was required for IFN-gamma-induced accumulation of HLA class II gene transcripts and played a role at a step subsequent to the transcriptional activation by IFN-gamma. Evidence was obtained which suggests that the putative protein factor(s) required was induced by IFN-gamma. These studies indicate that IFN-gamma regulates the expression of cellular genes through multiple pathways. PMID- 2109026 TI - [Clinical effects and immunological changes in interferon therapy for advanced renal cell carcinoma]. AB - alpha-type Interferon (INF-alpha A, MOR-22, HLBI) or gamma-type Interferon (GI-3) was administered intramuscularly to 18 patients with advanced renal cell carcinoma to examine its antitumor effect and immunological changes. All of these subjects had distant metastases and were subjected to Interferon therapy for more than 8 weeks. Tumor response according to the Koyama-Saito Team was PR, NC and PD in 4, 8 and 6 cases, respectively. In terms of the immunological changes in the peripheral blood before and after the Interferon therapy, NK cell activity showed increases for PR cases and decreases for NC and PD cases, with an obvious difference between Interferon-effective and -ineffective cases. For peripheral lymphocyte subpopulation, T-pan cell, T-helper cell and T-suppressor cell remained unchanged or tended to decrease. The difference in the change in NK cell activity observed between Interferon-effective and -ineffective cases suggested the involvement of NK cell activity in the efficacy of Interferon. PMID- 2109027 TI - [Enhanced cytotoxicity of antineoplastics by interferon]. AB - Cytotoxicities of bleomycin (BLM), vincristine (VCR) and adriamycin (ADM), and influence of interferon (IFN) on their effects were examined on three tumor cell lines of HeLa, HSG (established from human submandibular gland) and Muko cells (derived from mucoepidermoid tumor of the upper jaw). Both human natural interferon beta (IFN beta) and recombinant interferon gamma (IFN gamma) exhibited anticellular activities. Antiproliferative action, and DNA and protein synthesis inhibition of each anticancer drug on tumor cells were enhanced by a few hrs' IFN (100 IU/ml) pretreatment. In these, DNA synthesis inhibition was more exaggerated. Cooperative IFN effects were additive in general while showing slight synergistic inhibitory action on DNA synthesis. Enhanced in vitro cytotoxic effects of the anticancer drugs by IFNs were similarly identified in tumor cell-inoculated nu/nu mice which were treated twice a week with locally injected IFN gamma and antineoplastics. Proliferation of inoculated tumor cells was significantly suppressed by IFN gamma, and a cooperative effect of the IFN and drugs was obtained. Concentrations of intracellular anticancer drugs were heightened by IFN pretreatment. From these results, IFN seemed to contribute to the enhanced anticellular effects of BLM, VCR and ADM by affecting cellular uptake of the drugs. PMID- 2109028 TI - Factor IXa and von Willebrand factor modify the inactivation of factor VIII by activated protein C. AB - Activated protein C inactivates factor VIII by proteolytic cleavage of the heavy chain of factor VIII. Protein S and calcium ions are cofactors in this reaction. We have examined the effects of several potential modulators of this reaction, including phospholipids, von Willebrand factor, and factor IXa, all of which bind factor VIII. Our results indicate that neither resting nor stimulated platelets nor phospholipid vesicles protect factor VIII from inactivation by activated protein C in either the presence or the absence of protein S. However, the addition of von Willebrand factor decreases the inactivation of factor VIII by activated protein C by 20% to 30%, and factor IXa, which is known to protect factor VIII from inactivation by activated protein C, confers additional protection with von Willebrand factor. The active site of factor IXa is necessary for the protective effect, because native factor IX and active site-inhibited factor IXa do not protect factor VIII from inactivation. Thus there is an additive protective effect when von Willebrand factor and factor IXa are present with factor VIII, leading to a decrease in the inactivation by activated protein C. These factors may be particularly important in stabilizing factor VIII in the circulation and during the early stages of coagulation. PMID- 2109029 TI - Laryngeal amyloidosis. AB - Laryngeal amyloidosis is a rare disease. Surgery has been the mainstay of treatment either endoscopically or by an external neck approach. In more recent years, surgery with the carbon dioxide laser has been advocated for this condition. Four cases of laryngeal amyloidosis are presented. The application and the advantages of the carbon dioxide laser for the treatment of laryngeal amyloidosis are discussed. PMID- 2109030 TI - Interconversion of prebeta-migrating lipoproteins containing apolipoprotein A-I and HDL. AB - Mouse plasma from strains C57BL/6J and C3H/HeJ includes a high density lipoprotein (HDL) fraction containing apolipoprotein A-I which migrates in the prebeta region upon agarose gel electrophoresis, similar to the prebeta HDL previously reported in humans. This prebeta A-I lipoprotein species has a buoyant density of 1.080-1.210 g/ml and has two molecular weight species, 65,000 and 71,000. It is lipid-poor and deficient in apolipoprotein E. When mice are fed a high fat and high cholesterol diet, the quantity of prebeta A-I increases in both strains as determined by quantitative densitometry of agarose gel immunoblots. Prebeta A-I species are highly unstable in plasma at 37 degrees C. Initially (0-1 h) levels decreased and with further incubation (1-8 h) levels increased. Nondenaturing polyacrylamide gel electrophoresis (PAGE) demonstrated that the prebeta HDL formed during prolonged incubation (1-8 h) was identical in size to HDL in unincubated samples. The initial decrease of prebeta HDL observed during the first hour of incubation, phase I, was inhibited by DTNB, suggesting that phase I is dependent on lecithin:cholesterol acyltransferase (LCAT); however, the subsequent increase, phase II, was unaffected by DTNB and appears LCAT independent. The prebeta A-I species formed in plasma containing DTNB after a 4-h incubation resulted in a polydisperse particle size distribution. The two strains, the atherosclerosis-susceptible C57BL/6 and -resistant C3H, displayed a similar elevation and induction of prebeta HDL during a dietary switch from laboratory chow to an atherogenic diet with a transient peak occurring at 7 days even when total HDL in the susceptible strain was greatly reduced. PMID- 2109031 TI - Interactions of saturated, n-6 and n-3 polyunsaturated fatty acids to modulate arachidonic acid metabolism. AB - Anti-thrombotic effects of omega-3 (n-3) fatty acids are believed to be due to their ability to reduce arachidonic acid levels. Therefore, weanling rats were fed n-3 acids in the form of linseed oil (18:3n-3) or fish oil (containing 20:5n 3 and 22:6n-3) in diets containing high levels of either saturated fatty acids (hydrogenated beef tallow) or high levels of linoleic acid (safflower oil) for 4 weeks. The effect of diet on the rate-limiting enzyme of arachidonic acid biosynthesis (delta 6-desaturase) and on the lipid composition of hepatic microsomal membrane was determined. Both linseed oil- or fish oil-containing diets inhibited conversion of linoleic acid to gamma-linolenic acid. Inhibition was greater with fish oil than with linseed oil, only when fed with saturated fat. delta 6-Desaturase activity was not affected when n-3 fatty acids were fed with high levels of n-6 fatty acids. Arachidonic acid content of serum lipids and hepatic microsomal phospholipids was lower when n-3 fatty acids were fed in combination with beef tallow but not when fed with safflower oil. Similarly, n-3 fatty acids (18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3) accumulated to a greater extent when n-3 fatty acids were fed with beef tallow than with safflower oil. These observations indicate that the efficacy of n-3 fatty acids in reducing arachidonic acid level is dependent on the linoleic acid to saturated fatty acid ratio of the diet consumed. PMID- 2109032 TI - Evidence for cytokine regulation of cholesterol metabolism in herpesvirus infected arterial cells by the lipoxygenase pathway. AB - Cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and gamma interferon (IF) are produced by activated hematopoietic cells. They possess antiviral activity and have other biological activities such as induction of cell proliferation and hemorrhagic necrosis of tumors. Since herpes simplex virus (HSV) infection of human vascular cells is known to produce a biochemical and cytopathological effect virtually indistinguishable from atherosclerosis, we hypothesized that these cytokines many prevent cholesteryl ester (CE) accumulation in arterial smooth muscle cells (SMC) that is seen with herpesvirus infection. We now report that TNF and IL-1 but not gamma-IF prevent CE accumulation in HSV-infected arterial SMC by induction of cyclic AMP-dependent CE hydrolysis. This effect is mediated through the arachidonate 12-lipoxygenase pathway via 12-HETE since pretreatment of cells with several lipoxygenase inhibitors abolishes the antiviral effect and 12-HETE is the major (greater than 99%) lipoxygenase metabolite produced by these cells. This conclusion is further based on our observations that TNF and IL-1 enhance 12-HETE production in SMC and that 12-HETE significantly increases both intracellular cyclic AMP and lysosomal CE hydrolysis. Moreover, dibutyryl cyclic AMP restored a normal phenotype in these virally infected cells. Collectively, these findings identify for the first time a biochemical mechanism involved in the reduction of lipid accumulation in virally infected arterial SMC by these potent cytokines. PMID- 2109033 TI - Effect of temperature on cardiac vagal action in the toad Bufo marinus. AB - The effect of temperature on the action of the vagus nerve on the heart was studied in the toad Bufo marinus. Experiments were performed on two groups of toads, in one the heart was perfused at a constant rate with oxygenated Ringer's solution and in the other the circulation was left intact. In all toads there was a linear relationship between pulse interval (PI) and the frequency of vagal stimulation (fv) at any one temperature. The slope of this relationship changed with temperature, the effectiveness of the vagus (delta PI/delta fv) increasing with decreasing temperature. At low temperatures the vagus nerves of intact toads were more effective than in those with perfused hearts. It is suggested that, in intact toads at low temperatures, cardiac output decreases and the consequent accumulation of acetylcholine leads to increased vagal effectiveness. PMID- 2109034 TI - Reduced plasminogen activator inhibitor activity in high consumers of fruits, vegetables and root vegetables. AB - We studied a cross-sectional sample of 260 subjects aged 30-60 years, in order to assess the relation between food intake habits and factors of the fibrinolytic system. Plasma samples of tissue plasminogen activator (tPA) antigen, and plasminogen activator inhibitor (PAI-1) activity were obtained for the assay. The dietary pattern was determined using a food frequency questionnaire, according to which the subjects were grouped as high, low or medium consumers. The subjects who were high consumers of fruit, vegetables, and root vegetables showed the lowest levels of PAI-1, those who were low consumers had the highest levels, whereas the medium consumers showed intermediate values. The tPA levels did not differ between the three groups, and there were no significant differences in other variables that covaried with PAI-1 levels, such as age, anthropometric variables, or serum lipid levels, which could confound the PAI-1/food pattern relationship. The data, which show that a frequent intake of fruit, vegetables, and root vegetables--foodstuffs rich in vitamin C and fibre--is associated with lower PAI-1 levels, are consistent with increased activity of the fibrinolytic system and thus a reduced risk of thromboembolic and cardiovascular disease in subjects who exhibit this food intake pattern. PMID- 2109035 TI - Transgenic mice demonstrate that epithelial homing of gamma/delta T cells is determined by cell lineages independent of T cell receptor specificity. AB - gamma/delta T cells with different TCR repertoires are compartmentalized in different epithelia. This raises the possibility that the TCR-gamma/delta directs homing of T cells to these epithelia. Alternatively, the signals that induce TCR gamma/delta expression in developing T cells may also induce homing properties in such cells, presumably in the form of cell surface receptors. We have examined this issue by studying the homing of gamma/delta T cells in transgenic mice constructed with specific pairs of rearranged gamma and delta genes. In such mice, most gamma/delta T cells express the transgene-encoded TCR. We find that homing to both skin and gut epithelia is a property of T cells and is not determined by the type of gamma and delta genes used to encode their TCR. We also studied the effect of TCR replacement on the expression of Thy-1 and CD8 proteins on the gamma/delta T cells associated with gut epithelia. Our results show that the expression of the appropriate type of TCR-gamma/delta is not required for the Thy-1 expression by these T cells, suggesting that Thy-1 is not an activation marker. In contrast, CD8 expression by gut gamma/delta T cells seems to depend on the expression of the appropriate type of TCR. PMID- 2109036 TI - Roles of CD4+ and CD8+ cells, and the effect of administration of recombinant murine interferon gamma in listerial infection. AB - Studies were made on the effects of in vivo administration of anti-CD4 mAb, anti CD8 mAb, or a combination of both mAbs on multiplication of bacteria, the levels of serum transaminases, and mortality in mice infected with Listeria monocytogenes. Results showed that in sublethal infection, CD8+ cells enhanced the peak of bacterial multiplication and liver cell necrosis, and CD4+ cells suppressed CD8+ cell-mediated enhancement. Results also showed that either CD4+ or CD8+ cells were necessary for, and capable of, mediating clearance of the bacteria. CD8+ cells were more efficient than CD4+ cells, but for optimal clearance both were necessary. In lethal listeriosis, treatment of mice with anti CD8 mAb or a combination of both anti-CD4 and anti-CD8 mAbs, but not anti-CD4 mAb only, protected mice from death by decreasing multiplication of bacteria in the liver and spleen after a peak of approximately 10(8) CFU, and lowering the elevated serum levels of transaminases. These findings indicated that CD8+ cells were responsible for causing irreversible systemic Listeria infection and severe liver necrosis. In lethal listeriosis, administration of rMuIFN-gamma markedly prolonged survival by decreasing multiplication of bacteria and promoting recovery from liver necrosis. PMID- 2109037 TI - cis-acting sequences required for class II gene regulation by interferon gamma and tumor necrosis factor alpha in a murine macrophage cell line. AB - In this report, we have demonstrated that IFN-gamma and TNF-alpha increase expression of both the I-A and I-E region gene products on the surface of the myelomonocytic cell line WEHI-3, and that they mediate this increase via an increase in A alpha transcription. Constructs containing 5' deletion mutations of the A alpha promoter attached to the bacterial chloramphenicol acetyl transferase gene were used to delineate the minimum 5' flanking sequences required for promoter activity, and for inducibility by IFN-gamma and TNF-alpha. Approximately 115 bp of 5' sequences are required for minimum induction by IFN-gamma or TNF alpha when the cytokines are present separately. This includes the three conserved promoter elements, the X, Y, and H boxes. Nested linker-scanner mutations demonstrated that additional regions were also critical for optimal induction by IFN-gamma or TNF-alpha. These include the kappa B-like enhancer and a TNF-alpha-specific sequence that we have tentatively called the T box. The T box sequence was also found in the promoter regions of the human HLA-DQ alpha and rat RT1.B alpha genes. Although the entire T box sequence element was not found in the other mouse class II genes, all class II alpha genes contained the SV40 core enhancer element in the regions included by the T box. Mouse class II beta genes appear to contain neither the T box nor the core enhancer element in this region, suggesting differential regulation of class II alpha and beta genes by TNF-alpha. PMID- 2109038 TI - Purification of macrophage deactivating factor. AB - Macrophage deactivation factor (MDF) in P815 tumor cell-conditioned medium was assayed by its suppression of the ability of activated mouse peritoneal macrophages to release hydrogen peroxide. MDF displayed properties of a soluble protein(s) associated with both low (8-25,000) and high (greater than 450,000) Mr fractions. MDF was purified 6,140-fold by a seven-step procedure: extraction with acid-ethanol; precipitation with ether; and fractionation on gel filtration, anion-exchange, diphenyl reversed-phase and C4 reversed-phase HPLC columns, the last column twice. The final preparation contained two species: (a) a approximately 13,000 Mr band on reducing or nonreducing SDS-PAGE and on autoradiograms after radioiodination with chloramine T, and (b) a 66,000 Mr species ranging from approximately 5% to approximately 50% of the protein detectable by silver strain. The 66,000 Mr species was identified as albumin from its NH2-terminal amino acid sequence. However, no amino acid sequence could be obtained for the approximately 13,000 Mr species, either in fluid phase or after electroelution of the corresponding SDS-PAGE band. Thus, approximately 13,000 Mr MDF associates tightly with albumin through a variety of separation techniques, and may have a blocked NH2 terminus. Purified MDF afforded 50% inhibition of activated macrophage H2O2 releasing capacity at a concentration of 1-10 nM. Separation of MDF from most higher Mr moieties was associated with disproportionately small increases in specific activity, suggesting MDF might be partially inactivated by purification. As purified, MDF was approximately 1,000 fold less potent at deactivating macrophages than TGF-beta. Antibodies that neutralized the macrophage-deactivating effect of TGF-beta did not inhibit deactivation by MDF. PMID- 2109039 TI - The recognition event between virus and host cell receptor: a target for antiviral agents. PMID- 2109040 TI - Purification and biochemical characterization of chicken anaemia agent. AB - Chicken anaemia agent (CAA) was purified using differential centrifugation and successive cycles of equilibrium density gradient centrifugation using sucrose and CsCl. The purification method was dependent on the use of an antigen detecting ELISA based on a CAA-specific monoclonal antibody. Virus particles banded at a density of 1.33 to 1.34 g/ml in CsCl and measured 23.5 +/- 0.8 nm in diameter. Purified preparations contained one major polypeptide (Mr 50,000) and a single-stranded, circular DNA (2.3 kb). CAA shares some of the biochemical characteristics possessed by porcine circovirus and the virus associated with psittacine beak and feather disease. PMID- 2109041 TI - Further characterization of scrapie replication in PC12 cells. AB - The rat pheochromocytoma cell line, PC12, undergoes neuron-like morphological, biochemical and electrophysiological differentiation, in the presence of low concentrations of nerve growth factor (NGF). NGF-treated PC12 cells have been shown previously to support 139A scrapie agent replication. In the present report we extended these findings and analysed the cellular conditions necessary for agent replication. Following the infection of differentiated PC12 cells, scrapie replicated to relatively high titres as determined by an incubation period assay. The removal of NGF, which causes the gradual dedifferentiation of PC12 cells, resulted in the inability of scrapie to replicate. The scrapie infectivity detected in PC12 cultures is cell-associated and not released into the medium. Cells in infected cultures did not show any change in morphology when compared to cells in mock-infected cultures. Titration studies of scrapie infectivity in PC12 cells have indicated that up to 4 LD50 units per cell can be obtained although a yield of 1 LD50 per cell was more common. Using an approximate m.o.i. of 1, only differentiated PC12 cells supported 139A scrapie agent replication when compared to two other differentiated, neuronal cell types, indicating that PC12 cells are more susceptible to agent replication. These studies support further the suitability of using differentiated PC12 cells as an in vitro model to study scrapie agent replication. PMID- 2109042 TI - A baculovirus expression vector derived from the basic protein promoter of Autographa californica nuclear polyhedrosis virus. AB - The basic protein of Autographa californica nuclear polyhedrosis virus (AcMNPV) is associated with virus DNA in virion nucleocapsids and is produced in infected cells during the late phase of gene expression. A transfer vector was constructed containing the beta-galactosidase gene, under the control of a copy of the putative basic protein promoter, in place of the polyhedrin gene within the AcMNPV EcoRI fragment I. After cotransfection of Spodoptera frugiperda cells with the transfer vector and infectious AcMNPV DNA, polyhedrin-negative recombinant viruses were selected which expressed high levels of beta-galactosidase. Radiolabelling of infected cell proteins showed that beta-galactosidase was expressed at the same time as the viral basic protein, between 8 to 24 h post infection, with a peak synthesis at 12 to 15 h. These results demonstrated that the temporal regulation of the basic protein promoter was not affected by its position within the virus genome. Furthermore, a new baculovirus vector system is now available for high level expression of foreign genes at earlier times in infected cells. PMID- 2109043 TI - Identification of disialosyl paragloboside and O-acetyldisialosyl paragloboside in cerebellum and embryonic cerebrum. AB - The lacto series of glycolipids are only minor constituents in mammalian CNS and are found mostly during development. Expression of a significant amount (70 micrograms of neuraminic acid/g dry weight) of disialosyl-lacto-N neotetraosylceramide (LD1) in adult mouse cerebellum is reported for the first time in the nervous system. The structure of this ganglioside was determined by hydrolysis with various glycosidases, immunochemical tests, sugar and fatty acid analyses after permethylation and capillary GLC-mass spectrometry, sugar linkage analysis of permethylated alditol acetates, and fast-atom bombardment-mass spectrometry of the native ganglioside. The structure of LD1 was determined to be NeuAc-NeuAc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1 ceramide. The major fatty acid was 18:0, and the long-chain base was C18 sphingenine. Mouse cerebellum also contained O-acetyl-LD1 and several other O acetylated gangliosides as recognized by monoclonal antibodies ME311 and 3G5. The levels of LD1 and O-acetyl-LD1 in cerebellum increased during postnatal development. During development of the Purkinje cell degeneration mutant, pcd/pcd, the levels of both of these gangliosides in the cerebellum declined with the loss of Purkinje cells, a finding indicating that these gangliosides are primarily associated with Purkinje cells. In the cortex, LD1, O-acetyl-LD1, and O acetyl GD3, like GD3, are developmentally regulated antigens and are only expressed in the fetal cortex and not to any significant extent in the adult. PMID- 2109044 TI - Guanine nucleotide-binding protein regulation of microsomal phospholipase D activity of canine cerebral cortex. AB - The hydrolytic activity of microsomal phospholipase D from canine cerebral cortex was measured by a radiochemical assay using 1,2-dipalmitoyl-sn-glycerol-3 phosphoryl[3H]choline and 1-palmitoyl-2-[9,10(n)-3H]palmitoyl-sn-glycerol-3 phosphorylcholine as the exogenous substrates. Of several detergents tested, Triton X-100 was found to be the most effective in allowing expression of phospholipase D hydrolytic activity. The microsomal phospholipase D does not require any metal ion for its hydrolytic activity. Calcium and magnesium were slightly inhibitory between concentrations of 1 and 4 mM, but zinc was greatly inhibitory, causing a loss of greater than 90% activity at the 4 mM concentration. Non-hydrolyzable guanine nucleotide analogues such as guanosine 5' (3-O-thio)triphosphate and guanyl-5'-yl-(beta, gamma-methylene)diphosphonate but not guanosine 5'-(2-thio)diphosphate were able persistently to stimulate phospholipase D hydrolytic activity at micromolar concentrations. Guanosine 5'-(2 thio)diphosphate was capable of partially blocking guanosine 5'-(3-O thio)triphosphate stimulation of phospholipase D. Aluminum fluoride was able to cause a two- to threefold increase in hydrolytic activity of the phospholipase D. Cholera toxin had a stimulatory effect on the hydrolytic activity of phospholipase D, whereas islet-activating protein pertussis toxin had no effect. These results indicate that regulation of microsomal phosphatidylcholine phospholipase D activity by the guanine nucleotide-binding protein(s) in canine cerebral cortex may play an important role in signal transduction processes as well as in brain choline metabolism. PMID- 2109045 TI - Phosphorylation by protein kinase C of the muscarinic acetylcholine receptor. AB - Muscarinic acetylcholine receptors purified from porcine cerebrum were phosphorylated by protein kinase C purified from the same tissue. More than 1 mol of phosphate was incorporated per mole of receptor, with both serine and threonine residues being phosphorylated. Neither the degree nor the rate of the phosphorylation was affected by the presence or absence of acetylcholine. GTP sensitive high-affinity binding with acetylcholine was observed for muscarinic receptors reconstituted with GTP-binding proteins (Gi or Go), irrespective of whether muscarinic receptors or the GTP-binding proteins had been phosphorylated by protein kinase C or not. This indicates that the interaction between purified muscarinic receptors and purified GTP-binding proteins in vitro is not affected by their phosphorylation. PMID- 2109046 TI - GABAergic growth cones: release of endogenous gamma-aminobutyric acid precedes the expression of synaptic vesicle antigens. AB - Growth cone fractions isolated from neonatal [postnatal day 3 (P3)] rat forebrain contain GABAergic growth cones as demonstrated by immunofluorescence staining with monospecific antibodies to gamma-aminobutyric acid (GABA). HPLC analysis shows that GABAergic growth cones release this endogenous GABA when stimulated with high K+. Endogenous GABA release is Ca2(+)-independent and, in this respect, similar to that seen previously with [3H]GABA. Isolated growth cone fractions also exhibit a K(+)-stimulated, Ca2(+)-independent release of endogenous taurine. None of the other amino acids shown to be present in isolated growth cone fractions were released, including glutamate, aspartate, and glycine. A population of dissociated cerebral cortical neurones prepared from P1 rat forebrain were GABA-immunoreactive after 1 day in culture. The cell body, neurites, and growth cones of these neurones were all stained with GABA antibodies. At this time in culture, neurones did not stain with either of two antibodies to synaptic vesicle antigens, i.e., p65 and synaptophysin. Growth cones isolated from P3 rat forebrain were also not immunoreactive with these antibodies. After about 8 days in culture, when neurones had established extensive networks of long, varicose axons and elaborately branched dendrites, many neurones and their neurites were immunoreactive for GABA antibodies. At this time in culture, p65 and synaptophysin antibodies did stain neuronal cell bodies and particularly their varicose axons. Dendrites were not stained with synaptic vesicle antibodies. These results suggest that GABAergic neurones synthesize GABA during neurite outgrowth and that GABA is present in, and can be released from, the growth cones of these neurones. The presence of GABA in GABAergic growth cones is not associated with synaptic vesicles, which explains the Ca2+ independency of both endogenous and [3H]GABA release from these growth cones. PMID- 2109047 TI - Disappearing brain lesions, psychosis and epilepsy: a report of two cases. AB - The association between disappearing brain lesions, psychosis and epilepsy in two patients is reported for the first time. Mechanisms to explain the underlying pathogenesis are postulated. PMID- 2109048 TI - Serum lipids, lipoproteins and apolipoproteins in black patients with angiographically defined coronary artery disease. AB - The association between angiographically defined coronary artery disease (CAD) and serum lipids, lipoproteins, and apolipoproteins was evaluated in 151 black men and 245 black women. Patients with 70% or greater narrowing of at least one coronary artery or greater than or equal to 50% stenosis of the left main coronary artery (n = 179) were compared to those with lesions of less than 50% stenosis (n = 217) for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), LDL-C/HDL-C, triglycerides, apolipoprotein A-I, apolipoprotein B, and apolipoprotein A-I/B. A consistently more atherogenic pattern of lipids, lipoproteins, and apolipoproteins occurred only among the women. Using stepwise selection multiple logistic regression analysis, the ratio of apolipoprotein A-I/B (odds ratio = 0.38, 95% confidence limits 0.24-0.61) was the only statistically significant association of CAD in women, after adjusting for the effects of age, body mass index, and histories of smoking, hypercholesterolemia, hypertension, and diabetes. When stratified by median of total cholesterol, the ratio of apolipoprotein A-I/B was the most strongly associated with the presence of CAD in the lower half of the total cholesterol distribution (less than 208 mg/dl), whereas in the upper half of the total cholesterol distribution the total cholesterol/HDL-C ratio was more strongly associated with CAD. None of the variables studied was associated with CAD in men. These results support other studies suggesting that apolipoproteins may be better predictors of CAD. PMID- 2109049 TI - Hypermetabolism in the acute stage of hemorrhagic cerebrovascular disease. AB - Oxygen consumption (VO2), carbon dioxide production (VCO2), urinary nitrogen excretion, respiratory quotient, resting energy expenditure (REE), %REE, and the consumption rates of carbohydrate, fat, and protein (%CHO, %Fat, %Prot, respectively) were determined pre- and postoperatively by indirect calorimetry in 13 patients with ruptured intracranial aneurysms and 11 patients with hypertensive intracerebral hemorrhage in the acute stage. The preoperative VCO2, VO2, urinary nitrogen excretion, respiratory quotient, REE, and %REE were, respectively (mean +/- standard deviation): 171 +/- 46 ml/min, 203 +/- 56 ml/min, 10.3 +/- 1.7 gm/day, 0.84 +/- 0.01, 1397 +/- 389 Cal/day, and 129% +/- 8%. The values for VCO2, VO2, REE, and %REE were all increased above normal levels. The %Prot was increased to 26.1% +/- 9.1%. In the postoperative period, the VCO2, VO2, urinary nitrogen excretion, REE, and %REE significantly increased to: 186 +/ 44 ml/min, 229 +/- 56 ml/min, 14.8 +/- 2.9 gm/day, 1557 +/- 384 Cal/day, and 141% +/- 21%, respectively. The %Fat and %Prot also increased significantly, but the %CHO significantly decreased. Preoperatively, in the patients with ruptured intracranial aneurysms, there was a greater increase in %Prot in eight patients classified (according to Fischer) as having a Group 3 or 4 subarachnoid hemorrhage (SAH) on computerized tomography than in five patients classified as having a Group 1 or 2 SAH. In summary, increased metabolic expenditure, especially increased catabolism of protein and fat, is characteristic of accompanying hemorrhagic cerebrovascular disease, and there is an increase in consumption of fat and protein in the postoperative period. Lack of precise knowledge about the cause and consequences of these metabolic responses makes it impossible at present to judge the optimal extent of nutritional replacement. The hypermetabolic state should be taken into consideration when caring for these patients as it may cause weight loss, poor wound healing, and susceptibility to infection. PMID- 2109050 TI - A new radiochemical method to determine the stability constants of metal chelates attached to a protein. AB - A new method was developed to determine the stability constants of bifunctional chelates of indium (In) coupled to a protein. This method utilizes the displacement reaction between an indium complex and ferric ion. By measuring the position equilibrium constant 'K' of this reaction and knowing the stability constant of the corresponding ferric chelate, the overall formation constant of the indium chelate can be determined. Human serum albumin (HSA) was conjugated with ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) using their cyclic dianhydrides. A new method was developed to couple triethylenetetraminehexaacetic acid (TTHA) with HSA using Woodward's Reagent K. The chelating agents coupled to HSA were complexed with indium-114m-(114mIn) labeled indium and purified by dialysis or microcentrifugation. The stability constants of these indium complexes were determined at physiologic pH using ferric chelate of nitrilotriacetic acid (Fe-NTA) as the source of ferric ion. No significant differences were found between the stability constants of the indium chelates conjugated to protein and those of unconjugated species. PMID- 2109051 TI - Influence of pH adjustment agents on the biologic behavior of osmium-191 impurity in iridium-191m generator eluates. AB - The influence of four pH adjustment agents on the biologic behavior of osmium-191 (191Os) impurity in 191Os/191mIr generator eluates was studied. Extended body clearance and biodistribution studies were performed in mice. The solutions to be injected were obtained by eluting generators with a 0.9% NaCl solution at pH 1. The pH of these eluates was adjusted to 5-9 with succinate, phosphate, lysine or NaOH solution. Our results demonstrate that the biologic behavior of these generator eluates is significantly dependent on the agent used for pH adjustment. Buffering with lysine leads to the best results: (a) the mice show no adverse reaction after injection of 150 human doses and the body clearance is very rapid and (b) more than 75% I.D. at 24 hr postinjection. Preliminary calculations based on these results suggest a significant decrease in the estimated patient radiation dose when lysine buffered 191Os/191mIr generator eluates are used for radionuclide angiography. PMID- 2109052 TI - Staff nurse turnover costs: Part I, A conceptual model. AB - The impact of turnover is a major concern for the chief nurse executive. This study provides nurse administrators with information necessary to more fully understand the impact of turnover and assists them in developing and defending retention strategies. Part 1 addresses the conceptual model used to guide the study; Part 2 (May 1990) will discuss the application of the methodology to measure nursing turnover costs and the study's findings. PMID- 2109053 TI - Protein turnover in malnourished patients with cystic fibrosis: effects of elemental and nonelemental nutritional supplements. AB - To evaluate the relative efficacy of nonelemental versus semielemental enteral supplements for nutritional rehabilitation of cystic fibrosis (CF) patients, whole-body protein turnover using the [15N]glycine method was studied in nine malnourished CF patients during enteral feedings, in a block design study comparing a semielemental formula (Criticare), a higher protein density but nonelemental formula (Traumacal) (T), and a nonelemental formula that had been modified to become isocaloric and isonitrogenous to the semielemental formula (modified Traumacal, MT). No significant differences in rates of protein synthesis or catabolism were observed comparing the three formulas. However, the higher protein density nonelemental formula resulted in higher net protein deposition compared to the other two formulas (T + 0.42 g kg-1 10 h-1 versus 0.33 g kg-1 10 h-1 for Criticare and -0.59 g kg-1 10 h-1 for MT), although this was significant (p less than 0.05) for the MT versus T comparison only. This study lends support to the use of less expensive nonelemental formulas for the nutritional management of malnourished patients with CF. PMID- 2109054 TI - An evaluation with piglets of bovine milk, hydrolyzed bovine milk, and isolated soybean proteins included in infant milk formulas. I. Effect on organ development, digestive enzyme activities, and amino acid digestibility. AB - A study, using the piglet as a model for the human infant, was undertaken to determine the effect of the protein source of a milk formula on organ development, the activity of digestive enzymes, and the absorption of amino acids as measured at the terminal ileum and over the entire digestive tract. Three isocaloric liquid milk formulas containing equal amounts of either intact bovine milk, hydrolyzed bovine milk, or isolated soybean protein as the sole source of this nutrient and with equal levels of fat and carbohydrate were each given to six 14-day-old piglets over a 19-day period in a manner that mimicked human infant feeding practice. Following a 6-day metabolism study, the piglets were killed, their organs removed, and samples of digesta collected. The protein source of the milk-based formula did not affect (p greater than 0.05) the weight/unit body weight of the small intestine, large intestine, liver, or pancreas, but the relative weight of the kidneys was lower (p less than 0.05) for animals fed the intact bovine milk-based formula and that of the stomach was higher (p less than 0.01) for piglets receiving the isolated soybean formula. The activities of pepsin, intestinal trypsin and chymotrypsin and pancreatic chymotrypsin were not influenced (p greater than 0.05) by protein source, but piglets receiving the bovine milk-based formula had a lower level of activity (p less than 0.01) for pancreatic trypsin. The apparent ileal and fecal absorption of nitrogen was similar for the three milk-based formulas, the overall mean ileal absorption of nitrogen (+/- SE) being 89.0% (+/- 1.44). Excluding cystine, where ileal absorption was relatively lower (p less than 0.05) with the isolated soybean formula (86.7%) compared with the intact bovine milk (91.5%), protein source had little effect on the apparent absorption of essential amino acids. It was concluded that the replacement of intact cow's milk protein in human infant formulas by either hydrolyzed cow's milk or isolated soybean protein is unlikely to cause any major disturbance in the digestive process. PMID- 2109055 TI - Simultaneous surgery for bilateral congenital cataracts. AB - In about one third of patients congenital cataracts are bilateral. If the cataracts are dense, and the patient an infant, bilateral simultaneous cataract removal reduces anesthetic risk, hospital stay, and cost and allows earlier optical correction. This study represents a retrospective survey of 32 eyes (16 cases) with simultaneous surgery for bilateral congenital cataracts. Bilateral simultaneous surgery can be performed to avoid a second general anesthesia in infants who have bilateral dense congenital cataracts. PMID- 2109056 TI - Pharmacokinetics of diphenhydramine after dose ranging in nonpregnant ewes. AB - Studies were conducted to characterize the pharmacokinetics of diphenhydramine in nonpregnant ewes after iv administration of 25-, 50-, 100-, and 200-mg doses of diphenhydramine hydrochloride on a crossover basis. Plasma drug concentration versus time data exhibited multiexponential characteristics. The initial distribution half-life increased from 5 to 9 min and the elimination half-life from 34 to 68 min as the dose was increased. There was also an increase in the volume of distribution (from 3 to 6 L/kg) with increasing dose. The elimination half-life and the volume of distribution after a 200-mg dose were significantly greater than after a 25-mg dose. There was, however, a linear increase in AUC0 infinity as dose was increased. The average total body clearance (approximately 5 L/h/kg) remained unchanged regardless of dose. The free fraction of diphenhydramine determined by equilibrium dialysis averaged 0.229 +/- 0.080, and the extent of drug binding to plasma protein was independent of the drug concentrations encountered (30-780 ng/mL) in the nonpregnant sheep in vivo. Concentration-independent binding of the drug was also confirmed by in vitro binding studies over the drug concentration range 10-2000 ng/mL. Therefore, it appears that changes in the volume of distribution are likely to be a result of changes in tissue uptake or binding of the drug as a function of dose. PMID- 2109057 TI - Synthesis and structure-activity relationships of anti-inflammatory 9,10-dihydro 9-oxo-2-acridine-alkanoic acids and 4-(2-carboxyphenyl)aminobenzenealkanoic acids. AB - Eighteen test compounds, in three chemical series, were prepared as potential anti-inflammatory agents and evaluated by the rat hindpaw carrageenan-induced edema assay. The compounds, isosteric with known anti-inflammatory and antiallergic cyclo-oxygenase and lipoxygenase inhibitors, are 10-methyl-9,10 dihydro-9-oxo-2-acridinealkanoic acids, 9,10-dihydro-9-oxo-2-acridinealkanoic acids, and 4-(2-carboxyphenyl)aminobenzenealkanoic acids. Compounds within each of these series differ in the structure of the alkanoic acid side chain. Compounds containing the acetic acid and the branched 2-propionic acid side chain showed inhibition of carrageenan-induced edema. The activity of compounds with these side chains and the inactivity of those with carboxy, oxyacetic, thioacetic, and 3-propionic acid side chains is in accordance with the proposed template model of Appleton and Brown for the active site of cyclo-oxygenase, rather than with the alternative active site model proposed by Gund and Shen. One compound, (+-)-2-[N-(2-carboxyphenyl)-4-aminophenyl]propionic acid (3c), showed edema inhibition at 50 mg/kg po, comparable to that of an equivalent dose level of (+)-naproxen. Compounds 4a and 5a, which contain a carboxylic acid side chain, exhibited inhibition of soybean 12-lipoxygenase with IC50 values of 17.2 and 8.4 microM, respectively. The inhibition observed for the control drug, naproxen, was 24 microM. PMID- 2109058 TI - Stereoselective determination of flecainide in human plasma by high-performance liquid chromatography with fluorescence detection. AB - Enantiomers of a drug may differ in their pharmacological activities or their disposition constants. We now describe a stereoselective analytical method for the determination of the antiarrhythmic agent flecainide in plasma. The resolution of the enantiomers is achieved by high-performance liquid chromatography (HPLC) on a normal phase silica column following derivatization with the optically active reagent (-)-methyl chloroformate. The eluting diastereoisomers are monitored by fluorescence detection at an excitation wavelength of 305 nm and an emission wavelength of 340 nm. The limit of sensitivity for the assay is as low as 2.5 ng/mL for each enantiomer using 1 mL of plasma. A new liquid-liquid extraction procedure with high recovery (greater than 95%) and high selectivity is also reported. The intra- and interassay coefficient of variation for replicated analysis of spiked plasma samples is less than 4.0% and 7.0%, respectively. The method is suitable for single and multiple dose pharmacokinetic studies in healthy volunteers or in patients. PMID- 2109059 TI - Putative cerebral cortical involvement in the ventilatory response to inhaled CO2 in conscious man. AB - 1. The response of the diaphragm to both transcranial magnetic stimulation and electrical phrenic nerve stimulation was studied in thirteen normal subjects under conditions of either a 'reflex' drive to ventilation with inhaled CO2 or during volitional ventilation of similar magnitude. 2. The induced compound action potential in the diaphragm was recorded using an oesophageal electrode, and in some cases transdiaphragmatic pressure was recorded using oesophageal and gastric balloon catheters. 3. The response of the diaphragm to transcranial magnetic stimulation was invariably facilitated with volitional inspiration; there was either minimal or no response at functional residual capacity. 4. Facilitation with inspiration was also seen during a 'reflex' drive to ventilation with inhaled CO2 in the presumed absence of any volitional contribution to ventilation. A similar degree of facilitation was seen with voluntary ventilation of similar magnitude and pattern. 5. If the facilitation is predominantly a cortical phenomenon, then these results imply that there is a behavioural component in the previously supposed purely 'reflex' drive to ventilation with inhaled CO2. We also discuss the interpretation of these results if some of the facilitation occurs at the phrenic motoneurone. PMID- 2109060 TI - Two transient outward currents in histamine neurones of the rat hypothalamus in vitro. AB - 1. The transient outward current exhibited by the histamine neurones of the tuberomammillary nucleus was studied using the single-electrode voltage clamp technique in an in vitro rat hypothalamic slice preparation. 2. The transient outward current exhibited steady-state inactivation at the resting potential. Inactivation was removed by priming hyperpolarization with a V1/2 of -85 +/- 1.2 mV, while the V1/2 for activation was -60.3 +/- 2.1 mV. 3. The decay of the transient outward current was best fitted by two exponentials with time constants of 104 +/- 36 and 568 +/- 128 ms. These two components were provisionally termed IA,f and IA,s for the fast and slowly decaying currents, respectively. 4. Removal of inactivation was time dependent; inactivation was fully removed by hyperpolarizing pulses to -110 mV of 200 ms or greater duration. Removal of inactivation of IA,f was rapid, becoming complete with hyperpolarizing pre-pulses of 50 ms or greater, while removal of inactivation of IA,s was not complete until hyperpolarizing pre-pulses were 200 ms in duration. 5. The fast decaying current IA,f was selectively blocked by 1 mM-4-aminopyridine. Tetraethylammonium chloride (10 mM) had no effect on either IA,f or IA,s. 6. The inactivation curves for IA,s, determined both by using the values obtained from the amplitude of the computed slower exponential function as well as that of the current remaining in 1 mM 4-aminopyridine, were negative to those of IA,f. Similarly derived activation curves for IA,s were positive to those of IA,f. 7. Superfusion with a nominal 0 Ca2+ medium containing 10 mM-Mg2+ did not reduce the maximal transient outward current. 8. The reversal potential of IA,s with 2.5 mM-K+ in the medium was -95 +/- 3 mV; the reversal potential of IA,f was at least 15 mV negative to that of IA,s. 9. It is concluded that histaminergic tuberomammillary neurones possess at least two transient outward currents which can be distinguished on the basis of their rates of decay, 4-aminopyridine sensitivity, voltage dependence and reversal potentials. PMID- 2109061 TI - Agonist-evoked changes in cytosolic pH and calcium concentration in human platelets: studies in physiological bicarbonate. AB - 1. Cytosolic pH (pHi) and calcium concentration ([Ca2+]i) have been investigated in the presence and absence of physiological HCO3- in human platelets co-loaded with the fluorescent indicators BCECF and Fura-2. Basal pHi and changes evoked by butyrate, thrombin, platelet activating factor (PAF), ADP and phorbol ester were investigated, as were the effects of removing external Na+. 2. In the presence of physiological HCO3- and CO2, basal pHi was 7.02 +/- 0.04 compared with 7.15 +/- 0.05 in the absence of HCO3-. Estimated cytosolic buffering power was reduced from 35.6 +/- 3.0 to 14.5 +/- 0.4 mM/pH unit by the omission of HCO3-. 3. Thrombin evoked an immediate acidification of 0.03 +/- 0.01 pH units in the presence of HCO3- and 0.07 +/- 0.01 pH units in its absence. The acidifications were followed by a slow alkalinization. The final pHi was 0.10 +/- 0.01 units above basal in the presence of HCO3- and 0.08 +/- 0.02 units above basal in the absence of HCO3-. The initial acidification was significantly greater in the absence of HCO3-. The subsequent increase in pHi was similar in the presence and absence of this ion, but the calculated loss of proton equivalents was greater in the presence of HCO3-. 4. Replacement of extracellular Na+ with N-methyl-D glucamine resulted in a fall in basal pHi and abolished recovery from thrombin evoked acidification in both the presence and absence of HCO3-. 5. In the presence of HCO3-, PAF and ADP evoked an intracellular acidification similar to that caused by thrombin. However, with PAF and ADP, the subsequent recovery in pHi was slow and did not rise above basal levels. Phorbol dibutyrate, an activator of protein kinase C, evoked a similar elevation in pHi of 0.04 +/- 0.01 units over 3 min in the presence and absence of HCO3-. 6. Stopped-flow fluorimetric measurements were made of both BCECF and Fura-2 fluorescence in the presence of HCO3-. In the presence and absence of external Ca2+, thrombin-evoked rises in [Ca2+]i peaked before any cytoplasmic alkalinization occurred. ADP evoked rapid elevations in [Ca2+]i, but caused no alkalinization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2109062 TI - Light adaptation in cone photoreceptors of the salamander: a role for cytoplasmic calcium. AB - 1. Light adaptation has been studied in isolated red-sensitive cone photoreceptors of the salamander, using suction pipette recordings of circulating current. 2. In the presence of background illumination, the response to incremental dim flashes became desensitized according to the Weber-Fechner law. The recovery phase of the flash response was accelerated significantly, although the time-to-peak was reduced only slightly, and for dim backgrounds the rising phase was unaltered. 3. The role of cytoplasmic calcium concentration, Cai2+, in mediating cone adaptation was investigated by minimizing light-induced changes in Cai2+, either by incorporating calcium buffer into the cytoplasm or by exposing the outer segment to low-Ca2+, 0-Na+ solution. Both treatments appeared to slow dramatically or even to eliminate the onset of light adaptation in the cone. 4. When the low-Ca2+, 0-Na+ solution was presented in darkness, responses to subsequent illumination were affected in a characteristic manner: (i) the response-intensity relation was steepened and shifted to lower intensities, (ii) the response to a step of light could be predicted by integration and compression of the flash response, and (iii) the flash sensitivity declined steeply as a function of background intensity. 5. After extended exposure of the cone to bright backgrounds, the sensitivity in darkness failed to return to its original level. The flash response kinetics were faster and more biphasic than for dark adapted responses or for responses desensitized to a comparable degree by exposure to steady background illumination. 6. The results indicate that, in cones isolated from the pigment epithelium, the primary factor influencing the adaptational state of the cell is the cytoplasmic concentration of free calcium, but that at high intensities the effects of pigment bleaching are likely to be significant. PMID- 2109063 TI - Ca2(+)-activated K+ current involvement in neuronal function revealed by in situ single-channel analysis in Helix neurones. AB - 1. The properties of single calcium-activated potassium channels (or C-channels) were studied in cell-attached patches using the patch-clamp technique. Experiments were performed on identified Ca2(+)-dependent U cells in juvenile specimens (1-2 months old) of Helix aspersa. 2. The criteria used to identify C channels were based on comparison between macroscopic C-currents and currents reconstructed from unitary recordings. Both currents had a slow activation rate at large positive potentials which turned into fast activation after large Ca2+ entries. Both currents were blocked by intracellularly injected EGTA. 3. The unitary conductance in normal (5 mM) or reduced (0.5 mM) [K+]o ranged from 24 to 65 pS (mean +/- S.D., 48 +/- 13; n = 64). With 85-110 mM [K+]o, which is approximately equal to the internal [K+], the conductance was 64 pS and the reversal potential was approximately 0 mV. 4. C-channels in U cells were distributed in clusters of three to ten channels (mean 5.05 channels in seventy five patches). Calcium channels were present in patches containing clustered C channels. C-channels within clusters behaved independently. 5. With patch electrode containing 8 mM-calcium, C-channels opened transiently upon patch depolarization. Reopenings in quiescent depolarized patches were induced by whole cell spikes triggered by current pulses applied to an intracellular electrode. Apparent inactivation of C-channels in depolarized patches was in fact due to a decrease in [Ca2+]i resulting from inactivation of Ca2+ channels. 6. Calcium-free saline solutions in the patch electrodes prevented C-channels from opening upon patch depolarization. Entry of calcium through the surrounding membrane induced delayed openings in the patch. Peak opening probability Po occurred 330 +/- 30 ms after a brief Ca2+ entry with a lag period of 50-80 ms. With patch electrodes filled with Ca2(+)-containing saline solutions and under conditions which maximized C-channel opening, peak Po was reached in 20-50 ms. The same value was observed for the whole-cell C-current. 7. The peak Po at a given patch potential and in response to a whole-cell spike was not altered by a previous long-lasting patch depolarization, or by producing several successive Ca2+ entries. Thus, C channels did not appear to be inactivated by depolarization or increase in [Ca2+]i. 8. C-channels were found to be relatively highly voltage dependent, with an e-fold increase in Po per 14.9 mV increase in potential.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2109064 TI - Acute suppression of FSH secretion by oestradiol in the ovariectomized rhesus monkey. AB - Using long-term ovariectomized rhesus monkeys, we examined the ability of oestradiol to decrease circulating FSH concentrations in the absence of other ovarian factors. Daily blood samples were obtained from untreated monkeys for 8 days, followed by insertion of oestradiol capsules after the Day-8 sample was taken. Samples were then taken on Days 9-15, the capsules were removed after the Day-15 sample, and samples were obtained on Days 16-19. Serum was assayed for concentration of oestradiol, FSH and LH by RIA. The concentration of FSH (ng/ml) in serum did not change during the first 8 days before oestradiol treatment (overall mean = 356 +/- 55) but decreased from the Day-8 value of 320 +/- 8 to 190 +/- 42 on Day 9 and by Day 15, after 7 days of oestradiol treatment, had reached a nadir of 20 +/- 5. By Day 17, i.e. 2 days after removal of the oestradiol capsules, serum FSH had increased (P less than 0.05) to 92 +/- 23 with a further increase (P less than 0.05) on Day 19 (171 +/- 16). This study demonstrates that, unlike in rats, mice, and sheep, administration of oestradiol alone to ovariectomized rhesus monkeys reduces immunoreactive serum FSH to concentrations measured in intact animals. PMID- 2109065 TI - Partial characterization of the PAF-induced soluble factors which mimic the activity of 'early pregnancy factor'. AB - Platelet-activating factor (PAF) stimulated mouse spleen cells to release soluble factors (termed S2 factors) which were capable of inducing increased rosette inhibition titres when applied to fresh mouse spleen cells in the rosette inhibition assay. In this ability the S2 factors mimic that of pregnancy serum, an action previously ascribed to 'early pregnancy factor'. The PAF-stimulated production of these S2 factors was not influenced by inhibitors of cyclooxygenase metabolism, but was completely inhibited by the lipoxygenase inhibitors, diethyl carbamazine and nordihydroguaiaretic acid. The S2 factors had a lipid-like character in that they were extractable in organic solvents. The calcium ionophore A23187 also stimulated the production of these factors which may well be products of the lipoxygenase pathway of arachidonic acid metabolism. PMID- 2109066 TI - Effects of supraphysiological concentrations of progesterone on the characteristics of the oestradiol-induced gonadotrophin surge in women. AB - Intramuscular injections of oestradiol benzoate were given to 8 normally cyclic women in the early follicular phase of 3 different cycles. Progesterone was also injected in the second (low dose) and the third cycle (high dose). Oestradiol induced simultaneous surges of LH and FSH in all women and the onset of these surges was advanced by progesterone. Low-dose progesterone induced a significant increase in the amplitude and the duration of the LH and FSH surges, while high dose progesterone decreased the duration significantly. In contrast to the oestrogen-only treatment cycles, when the women were treated with progesterone, basal LH and FSH concentrations were suppressed significantly not only before the onset but also after the end of the surge. The results suggest that progesterone affects the dimension of the oestradiol-induced gonadotrophin surge by exerting both a stimulatory and an inhibitory effect on pituitary gonadotrophin secretion. Supraphysiological concentrations of progesterone decreased the duration of the oestradiol-induced gonadotrophin surge significantly and this is possibly part of the mechanism which attenuates the endogenous LH surge in women superovulated for in-vitro fertilization. PMID- 2109067 TI - Effect of ovariectomy at two periods of the year on LH and FSH basal concentrations and pituitary response to LHRH in the brown hare (Lepus europaeus). AB - In the brown hare, fertile mating takes place from the beginning of December to September. Seasonal variations of basal concentrations of LH and FSH, and pituitary response to a monthly i.v. injection of LHRH were studied in intact control females and in females ovariectomized during the seasonal anoestrus (OVX1) or during the breeding season (OVX2). In intact females, both basal and LHRH-stimulated LH levels showed an annual variation, with minimal values during anoestrus. During the breeding season, the LH response to LHRH exhibited a biphasic pattern. In contrast, there was no clear seasonal variation in basal and LHRH-stimulated FSH concentrations. After ovariectomy during anoestrus, basal LH remained low for 2 months and began to increase in December. After ovariectomy during the breeding season, LH basal concentrations increased within a few days after the operation. Thereafter, LH values remained high in both groups of females until September, and decreased significantly as in intact females. The pattern of LH release after LHRH remained monophasic in the two groups of ovariectomized females. In OVX1 females, the LH response increased as early as October, was maximum from December to April and decreased progressively until October. IN OVX2 females, the LH response decreased regularly after ovariectomy to a minimum in October. In the 2 groups of ovariectomized females, basal FSH concentrations and pituitary response to LHRH rose rapidly after ovariectomy and did not vary significantly thereafter. These results showed a direct central effect of season on the regulation of basal concentrations of LH, modulated by a negative feed-back of ovarian secretions during the breeding season. In intact hares, the enhanced LH response after LHRH during the breeding season was related to an acute positive effect of ovarian secretions. The regulation of FSH was less dependent on season and remained under a negative control of the ovary throughout the year. PMID- 2109068 TI - Testicular development and maturation of the hypothalamic-pituitary-testicular axis in the male tammar, Macropus eugenii. AB - Testicular growth and maturation of the hypothalamic-pituitary-testicular axis were assessed in male tammars from 12 to 25 months of age to establish the time of sexual maturity. The testicular dimensions and body weights of 20 male tammars, approximately 12 months of age at the beginning of the study, were measured monthly for 1 year. Groups of 3 animals were castrated at 13, 19 and 25 months of age and their testes sectioned for histological examination. Testicular volume increased between 12 and 24 months of age and was highly correlated with body weight (r = 0.91). In the 13-month group the seminiferous tubules were closed with few mitotic figures. Spermatogenesis had begun in 2 of the 19-month animals. All stages of spermatogenesis were present in the other 19-month male, and in all of the 25-month males. Basal FSH concentrations increased with the age of the animal (21.0 +/- 32.48, 94.40 +/- 55.18 and 193.05 +/- 40.21 ng/ml (mean +/- s.d.) at 19, 20 and 25 months respectively) while basal LH concentrations were similar at 20 months and 25 months (0.43 +/- 0.18 and 0.58 +/- 0.25 ng/ml respectively). Basal testosterone concentrations were also similar 0.11 +/- 0.04, 0.35 +/- 0.16 and 0.22 +/- 0.10 ng/ml in 13-, 19- and 25-month-old animals. LHRH injection in tammars at 13, 19 and 25 months of age induced release of both LH and testosterone 10-30 min after injection. The hormone concentrations increased in both magnitude and duration with increasing age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109069 TI - Resumption of gonadotrophin release during the post-partum period in suckling and non-suckling ewes. AB - The post-partum secretion of LH, FSH and prolactin was monitored in 15 suckling and 6 non-suckling Prealpes du Sud ewes lambing during the breeding season by measuring plasma hormone concentrations daily at 6-h intervals and also weekly at 20-min intervals for 6 h from parturition to resumption of regular cyclic ovarian activity. There was a constant phenomenon in the resumption of normal patterns of FSH and LH secretion: there was a rise in FSH values culminating on average on Day 4 post partum and returning subsequently to values observed during the oestrous cycle, and concurrently an increase in the frequency and amplitude of LH pulses more progressive in suckling than in non-suckling ewes which led to an elevation of LH mean concentrations and occurrence of an LH surge. Since neither the FSH secretory pattern nor FSH mean values differed between suckling and non suckling ewes, the results suggested that LH pulsatile pattern was a major limiting factor for the resumption of normal oestrous cycles. Before regular oestrous cycles resumed other changes in preovulatory LH surges also occurred: (i) they increased in duration and probably in amplitude; (ii) they were preceded by an acceleration in LH pulse frequency and a large decrease in FSH values as in normal cyclic ewes; and (iii) at least in non-suckling ewes they occurred concurrently with a prolactin surge. PMID- 2109070 TI - Seasonal cycles in the blood plasma concentration of FSH, inhibin and testosterone, and testicular size in rams of wild, feral and domesticated breeds of sheep. AB - Seasonal cycles in testicular activity in rams were monitored in groups of wild (mouflon), feral (Soay) and domesticated breeds of sheep (Shetland, Blackface, Herdwick, Norfolk, Wiltshire, Portland and Merino) living outdoors near Edinburgh (56 degrees N). The changes in the blood plasma concentrations of FSH, inhibin and testosterone, and the diameter of the testis were measured every half calendar month from 1 to 3 years of age. There were significant differences between breeds in the magnitude and timing of the seasonal reproductive cycle. In the mouflon rams, the seasonal changes were very pronounced with a 6-15-fold increase in the plasma concentrations of FSH, inhibin and testosterone from summer to autumn, and a late peak in testicular diameter in October. In the Soay rams and most of the domesticated breeds, the seasonal increase in the reproductive hormones occurred 1-2 months earlier with the peak in testicular size in September or October. In the two southern breeds (Portland and Merino), the early onset of testicular activity was more extreme with the seasonal maximum in August. In cross-bred rams, produced by mating Soay ewes (highly seasonal breed) with Portland or Merino rams (less seasonal breeds), there was a seasonal reproductive cycle that was intermediate compared to that of the parents. A comparison between all 11 breeds showed a significant correlation between the timing of the seasonal cycle in plasma FSH concentration and testicular diameter (time of peak FSH vs testis, r = 0.95). The overall results in the rams are consistent with a primary role of FSH in dictating the seasonal cycle in testicular size and the secretion of inhibin. The earlier seasonal onset in the testicular cycle in the southern breeds of domesticated sheep, and the differences from the wild type, are taken to represent the effects of genetic selection for a longer mating season. PMID- 2109071 TI - Effects of oestradiol on LH, FSH and prolactin in ovariectomized ewes. AB - This study was conducted to test the hypothesis that the rate (dose/time) at which oestradiol-17 beta (oestradiol) is presented to the hypothalamo-pituitary axis influences secretion of LH, FSH and prolactin. A computer-controlled infusion system was used to produce linearly increasing serum concentrations of oestradiol in ovariectomized ewes over a period of 60 h. Serum samples were collected from ewes every 2 h from 8 h before to 92 h after start of infusion, and assayed for oestradiol, LH, FSH and prolactin. Rates of oestradiol increase were categorized into high (0.61-1.78 pg/h), medium (0.13-0.60 pg/h) and low (0.01-0.12 pg/h). Ewes receiving high rates of oestradiol (N = 11) responded with a surge of LH 12.7 +/- 2.0 h after oestradiol began to increase, whereas ewes receiving medium (N = 15) and low (N = 11) rates of oestradiol responded with a surge of LH at 19.4 +/- 1.7 and 30.9 +/- 2.0 h, respectively. None of the surges of LH was accompanied by a surge of FSH. Serum concentrations of FSH decreased and prolactin increased in ewes receiving high and medium rates of oestradiol, when compared to saline-infused ewes (N = 8; P less than 0.05). We conclude that rate of increase in serum concentrations of oestradiol controls the time of the surge of LH and secretion of prolactin and FSH in ovariectomized ewes. We also suggest that the mechanism by which oestradiol induces a surge of LH may be different from the mechanism by which oestradiol induces a surge of FSH. PMID- 2109072 TI - Utility of fluoroimmunoassay in detecting luteinizing hormone surges in spontaneous and human menopausal gonadotropin-stimulated menstrual cycles. AB - Luteinizing hormone (LH) levels measured with radioimmunoassay and time-resolved fluoroimmunoassay (FIA) in 274 serum samples correlated highly, with a linear correlation coefficient of 0.934. Through the analysis of serial samples from 43 women undergoing human menopausal gonadotropin stimulation for in vitro fertilization or gamete intrafallopian transfer and seven patients monitored in spontaneous menstrual cycles for receipt of frozen embryos, we demonstrated the utility of FIA in the detection of the LH surge. This LH assay technique, which involves no radioactive isotopes, should facilitate the monitoring of ovulation induction patients in the office/ambulatory setting. PMID- 2109073 TI - Misoprostol in the prevention of NSAID-induced gastric ulcer: a multicenter, double-blind, placebo-controlled trial. AB - A multicenter, double-blind, placebo-controlled trial was undertaken to evaluate the efficacy of the synthetic prostaglandin E1 analog misoprostol in preventing and healing gastric ulcer induced by nonsteroidal antiinflammatory drugs (NSAID) in patients receiving chronic NSAID therapy for osteoarthritis (OA). A total of 420 patients with OA and NSAID-associated abdominal pain who were receiving ibuprofen, piroxicam or naproxen were enrolled in the study. Endoscopy was performed at study entry and after 1, 2 and 3 months of continuous therapy with misoprostol 100 micrograms, misoprostol 200 micrograms or placebo given q.i.d. while NSAID therapy was continued. Treatment failure was defined as development of gastric ulcer (greater than 0.3 cm in diameter). The occurrence of ulcer in each misoprostol group (5.6% and 1.4% for 100 micrograms and 200 micrograms, respectively) was significantly lower (p less than 0.001) than that in the placebo group (21.7%). The statistically significant difference persisted when comparisons were restricted to development of ulcer greater than 0.5 cm in diameter (12.3, 4.2 and 0.7% for placebo, misoprostol 100 micrograms q.i.d. and misoprostol 200 micrograms q.i.d., respectively). Mild-to-moderate, self-limiting diarrhea was the most frequently reported adverse event attributed to misoprostol use. PMID- 2109074 TI - Pharmacokinetics of misoprostol in the elderly, in patients with renal failure and when coadministered with NSAID or antipyrine, propranolol or diazepam. AB - The pharmacokinetics of misoprostol were examined in the following contexts: in coadministration with the nonsteroidal antiinflammatory agents (NSAID) aspirin, diclofenac, ibuprofen, indomethacin and piroxicam; in coadministration with agents extensively metabolized by the liver--i.e., antipyrine, propranolol and diazepam; in healthy elderly subjects; and in patients with various degrees of renal failure. No clinically important interactions between misoprostol and NSAID were observed. Similarly, no metabolic interactions between misoprostol and antipyrine, propranolol or diazepam were noted. Pharmacokinetic variable values in elderly subjects did not differ in a clinically significant manner from those in younger subjects. Finally, although values for some pharmacokinetic variables- maximum concentration of misoprostol acid, area under the concentration-time curve and elimination half-life--were increased in patients with renal failure compared with controls, these alterations do not warrant changes in misoprostol dosage. These factors are particularly relevant to safety of misoprostol administration in elderly individuals, who not only consume more NSAID than young adults, but are also more likely to have intercurrent nonarthritic illness requiring additional medication and potentially modifying drug kinetics. PMID- 2109075 TI - Experimental evidence of the benefit of misoprostol beyond the stomach in humans. AB - Nonsteroidal antiinflammatory drugs (NSAID) cause inflammation of the small intestine in 60 to 70% of patients receiving these drugs for more than 6 months. The importance of the inflammation lies in the associated complications of blood and protein loss and in the occasional development of unique small intestinal strictures requiring surgery. The pathogenesis of the inflammation is unknown. However, increased intestinal mucosal permeability due to NSAID appears to be a prerequisite; increased permeability allows exposure of the mucosa to lumenal toxins, which results in neutrophil chemotaxis and, hence, inflammation. In a study assessing the possible protective effect of misoprostol on indomethacin induced increased small intestinal permeability, 12 volunteers underwent combined absorption/permeability tests prior to and following administration of misoprostol and/or indomethacin. Indomethacin increased intestinal permeability significantly as assessed by 51Cr-EDTA/L-rhamnose urine excretion ratio, and concomitant administration of misoprostol produced a significant protective effect. These results conform to the suggestion that NSAID-induced changes in intestinal permeability may be due to an imbalance between mucosal prostaglandins and leukotrienes. Longterm studies of the coadministration of misoprostol with NSAID are indicated to assess whether this agent reduces the severity of NSAID enteropathy. PMID- 2109076 TI - Recent advances in defining the role of misoprostol in rheumatology. AB - Recent findings suggest that the prostaglandin E1 analog misoprostol may be associated with significant antiinflammatory and immunomodulatory effects. The addition of misoprostol to diclofenac significantly reduced the effective dose of the latter in the carrageenan acute inflammation rat model. A number of in vitro and animal studies have shown that misoprostol substantially increases the immunomodulatory effect of cyclosporine or steroids, and a study in renal transplant recipients revealed that the addition of this agent to cyclosporine and steroid treatment produced a significant improvement in renal function and a marked decrease in the incidence of graft rejection. Further, other recent data suggest that misoprostol may exert a protective effect against the damage to cartilage that appears to be induced by some nonsteroidal antiinflammatory drugs by decreasing the synthesis of cytokines. Further studies of misoprostol in these various contexts are warranted. PMID- 2109077 TI - Hyponatraemia and Moduretic-grand mal seizures. PMID- 2109078 TI - Kyphomelic dysplasia: the first 10 cases. AB - We report two sibs, the ninth and tenth cases of a distinctive familial skeletal dysplasia. Designated kyphomelic dysplasia, the condition is a short limbed dwarfism characterised by very short angulated femora, variable bowing of other long bones, irregular, flared metaphyses, restricted joint mobility, a small thorax and short trunk, a normal cranium and psychomotor development, and a tendency for the bowing to improve with age in survivors. The first born of our cases died of pneumonia at 2 1/2 months of age and is known to us by radiographs only. The second case was under our care from birth. He died aged 13 months after developing a pure red cell aplasia in the second half of infancy, which spontaneously recovered about the time of onset of his final illness. These cases are discussed in relation to previous reports. PMID- 2109079 TI - Direct inhibitory action of EGTA-Ca complex on reverse-mode Na/Ca exchange in Myxicola giant axons. AB - Giant axons from the marine annelid Myxicola infundibulum were internally dialyzed with solutions containing 22Na ions as tracers of Na efflux. In experiments performed in Li-substituted seawater, Na efflux that is dependent on external Ca ion concentration, [Ca2+]o, was measured using dialysis to maintain [Na+]i at 100 mM, which enhances the [Ca2+]o-dependent Na efflux component, (i.e., reverse-mode Na/Ca exchange). When dialysis fluid contained EGTA (1 mM) to buffer the internal Ca concentration, [Ca2+]i, to desired levels, Na efflux lost its normal sensitivity to external calcium. The inhibition was not simply due to the Ca-chelating action of EGTA to produce insufficient [Ca2+]i to activate Na/Ca exchange. The addition of EGTA inhibited Cao-dependent Na efflux even when a large enough excess of [Ca2+]i was present to saturate the EGTA and still produce elevated values of [Ca2+]i. Control experiments showed that these high values of [Ca2+]i resulted in normal Na/Ca exchange in the absence of EGTA. It is concluded that the presence of EGTA itself interferes with the manifestation of reverse mode Na/Ca exchange in Myxicola giant axons. PMID- 2109080 TI - Improvement of cholera toxin-catalyzed ADP-ribosylation by endogenous ADP ribosylation factor from bovine brain provides evidence for an unchanged amount of Gs alpha in failing human myocardium. AB - The aim of the present study was to investigate whether or not alterations of Gs alpha can be detected with cholera toxin-induced ADP-ribosylation in myocardial membranes from patients with heart failure. Therefore, Gs alpha was radiolabeled by cholera toxin-catalzyed (32P)ADP-ribosylation with (32P)NAD as substrate. In membranes from left ventricular myocardium of six patients with dilated cardiomyopathy classified as NYHA IV and three samples from two non-failing donor hearts, labeling was too weak to allow detection of possible changes in the amount of Gs alpha. Therefore, the cytosolic small molecular weight G protein ARF (ADP-ribosylation factor), a cofactor for cholera toxin-induced ADP-ribosylation of Gs alpha, was partially purified from bovine cerebral cortex. ARF activity was quantified by its ability to enhance auto-ADP-ribosylation of cholera toxin A1 subunit. Gs alpha was identified by comparing the ADP-ribosylation patterns of myocardial membranes, membranes prepared from human leukemia (HL 60) and S 49 mouse lymphoma wild type cells (45 kDa-band present) with membranes of the Gs alpha-deficient S 49 variant cyc- (45 kDa-band missing). In the presence of ARF, specific radiolabeling of the Mr 45,000 subtype of Gs alpha was markedly enhanced. The amounts of Gs alpha as measured by cholera toxin-dependent (32P) ADP-ribosylation in the presence of ARR were similar in failing and nonfailing human hearts. It is concluded that factors other than Gs alpha are responsible for the altered regulation of the adenylate cyclase complex in heart failure. Moreover, by enhancing cholera toxin-catalyzed ADP-ribosylation, endogenous ADP ribosylation factor from bovine brain appears to be a useful tool to study Gs alpha even in tissues in which the labeling of Gs alpha is rather weak. PMID- 2109081 TI - Effects of calcium depletion and loading on injury during metabolic inhibition of isolated adult rat myocytes. AB - The hypothesis that calcium influxes from the extracellular space play an important role in the pathogenesis of irreversible anoxic injury was tested using isolated adult rat myocytes. Myocytes treated with 6 mM amytal and 3 mM iodoacetate and subsequently incubated in either calcium-containing (1.12 mM) or calcium-free media (with or without 1 mM EGTA) developed rigor contracture (cell squaring) and cell death (trypan blue permeability) at the same rate. The rates of cell death in both calcium-containing and calcium-free media were increased by incubation in hypotonic media even though the rates of contracture development remained unaltered. Cells developed osmotic fragility prior to membrane permeability increases. The calcium ionophore, A23187 (10 microM), induced rapid rounding of rod-shaped cells subjected only to mitochondrial inhibition in calcium containing media, confirming its ability to cause an increase in cellular permeability to calcium. However, A23187 did not alter the rates of cell death of totally metabolically inhibited myocytes in either calcium-containing or calcium free media with EGTA. The results indicate that influxes of calcium are not necessary for the development of irreversible injury in metabolically inhibited, isolated myocytes. PMID- 2109082 TI - The C.S.E.O.L. Conference on DNA-DNA Hydridization and Evolution. Lake Arrowhead, California, May 11-14, 1989. Proceedings. PMID- 2109083 TI - Comment on DNA hybridization issues raised at Lake Arrowhead. PMID- 2109084 TI - The future of DNA-DNA hybridization studies. AB - This article draws on many vertebrate examples to assess the future of DNA-DNA hybridization studies. I first discuss whether applications of the method have reached the point of diminishing returns, or rather the start of a great leap forward, in our evolutionary understanding. Vertebrate groups whose relationships are especially likely to be illuminated include parrots, pigeons, bats, pinnipeds, mammalian carnivores, frogs, and rodents. There are at least two reasons why classifications based on DNA-DNA hybridization may prove to differ from classifications based on particular character, whether these be noncoding DNA sequences or protein sequences or anatomical characters. Because evolutionary relationships can now be deduced independently of anatomical characters, this should permit a renaissance in comparative anatomical studies of adaptation. The origin of major functional shifts from changes in a small fraction of the genome is illustrated by polar bears, sea otters, warblers, vultures, and especially by humans. PMID- 2109085 TI - DNA hybridization evidence of hominoid phylogeny: a reanalysis of the data. AB - Sibley and Ahlquist (1984, 1987) presented the results of a study of 514 DNA-DNA hybrids among the hominoids and Old World monkeys (Cercopithecidae). They concluded that the branching order of the living hominoid lineages, from oldest to most recent, was gibbons, orangutan, gorilla, chimpanzees, and human. Thus, a chimpanzee-human clade was indicated, rather than the chimpanzee-gorilla clade usually suggested from morphological evidence. The positions of the gibbon and orangutan branches in the phylogeny are supported by substantial evidence, but whether the chimpanzee lineage branched most recently from the human lineage or from the gorilla lineage remains controversial. The conclusions of Sibley and Ahlquist (1984, 1987) have been supported by several independent studies cited by Sibley and Ahlquist (1987), plus the DNA sequence data of Hayasaka et al. (1988), Miyamoto et al. (1988), Goodman et al. (1989, 1990), and the DNA-DNA hybridization data of Caccone and Powell (1989). The laboratory and data analysis methods have been criticized by Marks et al. (1988) and Sarich et al. (1989). In response to these critics, and for our own interests, we present a reanalysis of the Sibley and Ahlquist data, including a description of the corrections applied to the "raw counts." The validity of the laboratory methods is supported by the congruence of tree topology and delta values with those of Caccone and Powell (1989), although their tetraethylammonium chloride technique differs from the hydroxyapatite method in several respects. The utility of the T50H distance measure is indicated by its congruence with percent sequence divergence at least to delta T50H 30, as noted by Goodman et al. (1990). The Sibley and Ahlquist uncorrected data indicate that Pan is genetically closer to Homo than to Gorilla, but that Gorilla may be genetically closer to Pan than to Homo. Melting curves are presented for the pertinent experiments, plus one that includes representatives of most of the groups of living primates. PMID- 2109086 TI - DNA hybridization as a guide to phylogeny: chemical and physical limits. AB - The technique of forming interspecific DNA heteroduplexes and estimating phylogenetic distances from the depression in their duplex melting temperature has several physical and chemical constraints. These constraints determine the maximum phylogenetic distance that may be estimated by this technique and the most appropriate method of analyzing that distance. Melting curves of self renatured single copy primate DNAs reveal the presence of components absent from the renaturation products of exactly paired sequences. This observation, which confirms existing literature, challenges a fundamental assumption: that orthologous (i.e., corresponding) DNA sequences in the divergent species are being compared in DNA heteroduplex melting experiments. As a model system, the thermal stabilities of heteroduplexes formed between a human alpha-globin cDNA and four alpha-like globin genes isolated from chimpanzee are qualitatively compared. The results of this comparison show that the cross-hybrids of imperfectly matched gene duplicates from divergent species can contribute to the additional components that are present in renatured single copy DNAs. Single copy DNA, as usually defined, includes sequence duplicates that will obscure phylogenetic comparisons in a mass hybridization of genomes. PMID- 2109087 TI - Primate evolution at the DNA level and a classification of hominoids. AB - The genetic distances among primate lineages estimated from orthologous noncoding nucleotide sequences of beta-type globin loci and their flanking and intergenic DNA agree closely with the distances (delta T50H values) estimated by cross hybridization of total genomic single-copy DNAs. These DNA distances and the maximum parsimony tree constructed for the nucleotide sequence orthologues depict a branching pattern of primate lineages that is essentially congruent with the picture from phylogenetic analyses of morphological characters. The molecular evidence, however, resolves ambiguities in the morphological picture and provides an objective view of the cladistic position of humans among the primates. The molecular data group humans with chimpanzees in subtribe Hominina, with gorillas in tribe Hominini, orangutans in subfamily Homininae, gibbons in family Hominidae, Old World monkeys in infraorder Catarrhini, New World monkeys in semisuborder Anthropoidea, tarsiers in suborder Haplorhini, and strepsirhines (lemuriforms and lorisiforms) in order Primates. A seeming incongruency between organismal and molecular levels of evolution, namely that morphological evolution appears to have speeded up in higher primates, especially in the lineage to humans, while molecular evolution has slowed down, may have the trivial explanation that relatively small genetic changes may sometimes result in marked phenotypic changes. PMID- 2109088 TI - The TEACL method of DNA-DNA hybridization: technical considerations. AB - This paper emanated from a conference concerning the value, accuracy, and technical considerations of DNA-DNA hybridization for evolutionary studies. Our laboratory has been performing the so-called TEACL (tetraethylammonium chloride) method, and we have amassed sufficient data to indicate that this method is very powerful if performed properly with correct analyses. Here we address five technical considerations: (1) We present empirical data that size correction for tracer length is legitimate and accurate. (2) We show that the error of delta Tm measurement does not significantly increase with increasing distance up to at least 10 degrees C. (3) The error distribution for delta Tm does not deviate from the expected normal distribution indicating parametric statistics are probably legitimate for analyses. (4) Using a known phylogeny we examined the resolving power of the technique by showing that at least five taxa can be correctly placed in phylogenies with a maximum delta Tm of 2.5 degrees C. (5) To date, all our data sets based on DNA-DNA hybridization are very robust with respect to analytical procedures in that every algorithm used on the data sets has yielded identical trees with nearly identical branch lengths. Nevertheless, we point out that theoretical analyses of distance data (as generated by DNA-DNA hybridization) are lacking, especially with regard to tests of the molecular clock hypothesis. PMID- 2109089 TI - Extreme rates and heterogeneity in insect DNA evolution. AB - DNA-DNA hybridization studies of insects, more specifically Drosophila and cave crickets, have revealed interesting patterns of genome evolution that contrast markedly with what has been seen in other taxa, especially mammals and birds. Insect genomes are composed of sections of single-copy DNA with extreme variation in rates of evolutionary change. This variation is more extreme than between introns and exons; introns fall into the relatively conserved fraction of the genome. Attempts to calculate absolute rates of change in Drosophila DNA have all led to estimates some 5-10 times faster than those found in most vertebrates; this is true even for the more conservative part of the nuclear genome. Finally we point out that morphological similarity, chromosomal similarity, and/or ability to form interspecific hybrids is often associated with quite high levels of single-copy DNA divergence in insects as compared to mammals and birds. PMID- 2109090 TI - Rapid evolution in a fraction of the Drosophila nuclear genome. AB - Previous observations have indicated that Drosophila DNA contains a component that evolves so rapidly that it fails to hybridize between the DNAs of sibling species. To establish the reality of this component and study its properties, the fraction (about 20%) of Drosophila simulans (Dsim) DNA that fails to hybridize to Drosophila melanogaster (Dmel) DNA has been isolated. The majority of the hybridizable part of this isolated fraction (based on control tests on Dsim DNA) fails to hybridize with Dmel DNA under the conditions used for the initial fractionation. Clones of this fraction do hybridize with Dmel DNA at open criterion producing duplexes with greatly reduced thermal stability, indicating that the underlying process is rapid sequence divergence rather than loss of the homologous sequences by relatively large deletions. Cloned fragments from the nonhybridizing fraction from Dsim are more than 15% divergent from the Dmel homologues, whereas the fraction that does hybridize is only 3-5% divergent. In comparison, synonymous substitutions in the coding regions of five genes show a 9% average divergence between Dsim and Dmel. They appear to be intermediate in their degree of divergence between the hybridizing and nonhybridizing components. PMID- 2109091 TI - DNA hybridization, cladistics, and the phylogeny of phalangerid marsupials. AB - Single-copy DNA/DNA hybridization experiments and numerical cladistic analyses of anatomical characters were used to investigate relationships among nine phalangerid (Marsupialia) species from four different genera. Both rate-dependent and rate-independent analyses of molecular data indicate that species of Trichosurus from one clade and that Strigocuscus, Phalanger, and Spilocuscus form a second. Within the latter group, Spilocuscus is excluded from a Strigocuscus Phalanger clade, which, in turn, is not fully resolved on a jackknife strict consensus tree. Minimum-length Dollo, Wagner, and Camin-Sokal parisomy trees based on 35 anatomical characters, in contrast, suggest placement of Strigocuscus with Trichosurus rather than with Spilocuscus and Phalanger. However, there are two derived characters that support the alternative arrange of Strigocuscus with Spilocuscus and Phalanger and one character that further unites Strigocuscus and Phalanger. Thus, DNA hybridization results are not inconsistent with the distribution of derived character states among anatomical characters, only with minimum-length trees based on character data. PMID- 2109092 TI - Effects of murine tumor class I major histocompatibility complex expression on antitumor activity of tumor-infiltrating lymphocytes. AB - Tumor-infiltrating lymphocytes (TILs) are T cells that can be grown from enzyme digested murine or human tumors. When adoptively transferred to tumor-bearing hosts concurrent with the administration of recombinant interleukin-2 (rIL-2), TILs can mediate significant regression of tumor. To examine whether expression of class I major histocompatibility complex on tumor cells influenced the generation and antitumor activity of TILs, we used clones of murine B16BL6 melanoma either transfected with or lacking the class I gene Kb to generate TILs at a high dose (1,000 U/mL) or at a low dose (20 U/mL) of human rIL-2. TILs grew from both tumors in high-dose rIL-2, but they grew from the class I-expressing tumor only in low-dose rIL-2. TILs from the class I-deficient tumor did not lyse any target tested in vitro, nor did they demonstrate any therapeutic effect in vivo on established tumors that lacked or expressed class I. In contrast, TILs from the class I-expressing tumor specifically lysed the tumor of origin in vitro and caused it to regress in vivo. Further, these TILs demonstrated activity in vitro against the non-class I-expressing melanoma treated with the combination of murine recombinant interferon gamma and human recombinant tumor necrosis factor alpha; in vivo, when administered with recombinant interferon gamma and recombinant tumor necrosis factor alpha, TILs from the class I-expressing tumor mediated regression of non-class I-expressing pulmonary metastases, presumably by augmenting class I expression. PMID- 2109093 TI - Endothelial cell production of nitrogen oxides in response to interferon gamma in combination with tumor necrosis factor, interleukin-1, or endotoxin. AB - Clinical studies using biological response modifiers in cancer therapy have shown that the major dose-limiting toxic effects are hypotension and diffuse microvascular leakage. The cause and pathophysiology of this hypotension remains unknown. Previous experiments have demonstrated that a number of cell types, including endothelial cells, neutrophils, and macrophages, can secrete a potent hypotensive agent--endothelium-derived relaxing factor, which has recently been identified as nitric oxide. In this study, we tested interferon gamma, tumor necrosis factor, interleukin-1, interleukin-2, muramyl dipeptide, and endotoxin for their effects on production of nitrogen oxides by endothelial cells. Interferon gamma, in combination with tumor necrosis factor, interleukin-1 (IL 1), or endotoxin, induced murine brain endothelial cells to secrete nitrites (20 45 microM within 48 hr), which are breakdown products of nitric oxide. Nitrite production was blocked by incubation of endothelial cells in medium without L arginine, a substrate for nitric-oxide synthase. Accumulation of nitrites was also inhibited by addition of NG-monomethyl-L-arginine (L-NMMA), which acts as a competitive inhibitor of this enzyme. The inhibitory effects of L-NMMA were reversed by addition of excess L-arginine. These results suggest (a) that endothelial cells produce nitric oxide in response to immunomodulators and (b) that endothelial cell-derived nitric oxide plays a role in the development of hypotension in patients treated with tumor necrosis factor or interleukins. Furthermore, administration of substrate analogues such as L-NMMA may favorably alter the toxicity associated with these immunomodulators and result in a higher maximum tolerated dose, with subsequent improvement in the antitumor activity. PMID- 2109094 TI - The Alzheimer's amyloid precursor protein is produced by type I astrocytes in primary cultures of rat neuroglia. AB - The production of beta-amyloid precursor protein (beta APP) by primary mixed glial cell cultures from cerebral cortex of 2-3 day postnatal rats was examined by Northern and Western blotting and by immunocytochemistry. A single 3.5 kb beta APP RNA transcript was detected using probes recognizing all forms of beta APP messenger RNA. No signal was detected with a probe specific for the alternately spliced Kunitz protease inhibitor (KPI) region. In Western blot analysis of protein extracts, antisera specific for either the cytoplasmic or extracellular parts of beta APP detected several proteins ranging from 105 to 140 kDa. None of these were recognized by an antiserum specific to the KPI insert of the beta APP. Multicolor immunofluorescence showed beta APP immunoreactivity in type I (GFAP+ A2B5-) astrocytes, distributed in a fibrillar pattern like that of glial fibrillary acidic protein (GFAP). No beta APP immunoreactivity was detected in oligodendrocytes (GC+) or in A2B5+ progenitor cells. Moreover, no cultured cells showed immunostaining with an antiserum specific for the KPI sequence of beta APP. We conclude that type I astrocytes in primary culture produce amyloid precursor protein, but that oligodendrocytes and their precursors do not. Moreover, type I astrocytes produce predominantly the beta APP subtypes which lacks the KPI sequence. PMID- 2109095 TI - Wound endotoxin is not a principal mediator of postburn hypermetabolism in rats. AB - Localized bacterial colonization of a 30% total body surface burn (TBSB) wound raises the resting metabolic rate of rats. To determine whether endotoxin (LPS) released in the burn wound contributes to this response, the metabolic rates and colonic temperatures of male Sprague-Dawley rats were monitored before and for 1 week after thermal injury. Wounds were seeded with non-virulent P. aeruginosa (NVP), or S. epidermidis (SE) or were left unseeded at the time of injury. Non bacteremic SE-seeded rats were as hypermetabolic as the NVP-seeded animals on postburn days (PBDs) 3-4 and 7-8, indicating that wound LPS is not an obligatory mediator of postburn hypermetabolism. Continuous subcutaneous infusion of NVPlps (2.6 and 12.6 micrograms/100 gm/hr) beneath unseeded burn wounds did not raise metabolic rates above those of burned, unseeded controls. Neither NVP seeding nor LPS infusion resulted in measurable endotoxemia on PBDs 7-8. These results indicate that the LPS released in the colonized burn wound does not serve as either a circulating mediator or the principal inducer of other mediators of postburn hypermetabolism in rats. PMID- 2109096 TI - Long-term persistence of toxigenic Vibrio cholerae 01 in the mucilaginous sheath of a blue-green alga, Anabaena variabilis. AB - Cholera epidemics occur twice a year in the endemic area of Bangladesh. Vibrio cholerae 01 can be isolated from the environment only during the epidemics and the question of possible interepidemic environmental reservoirs of V. cholerae remains open. The present laboratory-based studies investigate the role of an aquatic alga, Anabaena variabilis, as a possible reservoir. Persistence of V. cholerae inside the mucilaginous sheath of A. variabilis was observed by phase contrast and fluorescent microscopy for more than 15 months after inoculation. PMID- 2109097 TI - Epidemiology of male urethritis in Nigeria. AB - One thousand and seventy-two symptomatic male cases of urethritis were investigated. Of these, 643 (60%) had gonococcal aetiology; 579 (54%) of all cases were in the 21-30-year age group while only 21 (2%) were above 50 years and 654 patients were married, 418 unmarried. Traders, civil servants and students accounted for 33.8, 29.5 and 26.7% of cases respectively. Sokoto state of Nigeria was less affected with the disease than other areas. Three hundred and eighty-six patients gave a history of previous therapy and only 183 of these yielded gonococci. Seventy-two per cent of gonococcal isolates were penicillinase producers. It appeared that the social, cultural and religious beliefs of the local population had tremendous influence on the incidence of the disease. PMID- 2109098 TI - Mutations of RNA and protein sequences involved in human immunodeficiency virus type 1 packaging result in production of noninfectious virus. AB - To identify RNA and protein sequences involved in packaging of human immunodeficiency virus type 1 (HIV-1), various mutations were introduced into the viral genome. Portions of the human immunodeficiency virus type 1 genome between the first splice donor site and the gag initiation codon were deleted to investigate the RNA packaging site (psi). Point mutations that alter cysteine residues in one or both zinc finger motifs of p7, a cleavage product of the gag precursor, were created to study the role of the gag zinc fingers in packaging. The psi site mutants and the gag mutants exhibited similar phenotypes. Cells transfected with the mutant genomes, while expressing normal levels of human immunodeficiency virus type 1 RNA and proteins, produced viral particles that were normal in protein content but lacked detectable viral RNA. These mutant virions were unable to productively infect cells. The combination of human immunodeficiency virus type 1 packaging mutations should minimize fortuitous assembly of infectious virus and may provide a means to produce noninfectious particles for candidate vaccines. PMID- 2109099 TI - Presence and transcription of intracisternal A-particle-related sequences in CHO cells. AB - We have characterized sequences expressed in Chinese hamster ovary (CHO) cells which are related to the intracisternal A-particle (IAP) genes of mice and Syrian hamsters. Several cDNA clones homologous to Syrian hamster IAP probes have been isolated and used to evaluate the abundance and expression of these retroviruslike sequences. DNA blot analysis with homologous Chinese hamster IAP probes revealed that IAP-related sequences are present in CHO cell DNA at moderately repetitive levels (approximately 300 copies per haploid genome). Sequence analysis has revealed the existence of at least two distinct families of IAP-related sequences in CHO cell DNA. Family I sequences exhibit identical 4.5 kilobase-pair internal deletions relative to complete IAP genomes of mice or Syrian hamsters, but family II sequences showed no major sequence discontinuities relative to the IAP genes of other species. Both families are expressed as abundant cytoplasmic RNA in CHO cells, but only family II sequences produce abundant transcripts of a size consistent with that of a full-length IAP RNA. Intact gag, pol, or env open reading frames were not present in sequences of either family, although incomplete open reading frames spanning putative p27 and protease regions of IAP genes were observed. PMID- 2109100 TI - Human immunodeficiency virus envelope glycoprotein/CD4-mediated fusion of nonprimate cells with human cells. AB - Human immunodeficiency virus (HIV) infects human cells by binding to surface CD4 molecules and directly fusing with the cell membrane. Although mouse cells expressing human CD4 bind HIV, they do not become infected, apparently because of a block in membrane fusion. To study this problem, we constructed a recombinant vaccinia virus that can infect and promote transient expression of full-length CD4 in mammalian cells. This virus, together with another vaccinia recombinant encoding biologically active HIV envelope glycoprotein gp160, allowed us to study CD4/gp160-mediated cell-cell fusion in a wide variety of human and nonhuman cells in the absence of other HIV proteins. By using syncytium formation assays in which a single cell type expressed both CD4 and gp160, we demonstrated membrane fusion in lymphoid and nonlymphoid human cells but not in any of the 23 tested nonhuman cell types, derived from African green monkey, baboon, rabbit, hamster, rat, or mouse. However, in mixing experiments with one cell type expressing CD4 and the other cell type expressing gp160, all of these nonhuman cells could form CD4/gp160-mediated syncytia when mixed with human cells; in 20 of 23 cases, membrane fusion occurred only if the CD4 molecule was expressed on the human cells whereas in the other three cases, CD4 could be expressed on either one of the fusing partners. Interestingly, in one mouse cell line, CD4-dependent syncytia formed without a human partner, but only if a C-terminally truncated form of the HIV envelope glycoprotein was employed. Our results indicate that nonhuman cells are intrinsically capable of undergoing CD4/gp160-mediated membrane fusion, but this fusion is usually prevented by the lack of helper or the presence of inhibitory factors in the nonhuman cell membranes. PMID- 2109101 TI - Assembly of gag-beta-galactosidase proteins into retrovirus particles. AB - We studied the expression of beta-galactosidase (beta-gal) and 15 gag-beta-gal fusion proteins in the presence of Moloney murine leukemia virus wild-type core (gag) proteins. Analysis indicated that proteins retaining the amino-terminal portion of gag through the capsid protein-coding region were incorporated into retrovirus particles. Proteins which deleted portions of the capsid protein were assembled into virions at low efficiency, indicating the importance of capsid protein interactions in retrovirus assembly. Fusion proteins which retained the amino-terminal matrix protein of the gag polyprotein but which lacked the capsid protein were released efficiently from cells in a nonviral form. The nonviral form was characterized by a high sedimentation coefficient and a low density, suggestive of membrane vesicles. While beta-gal was present in the cytoplasm of expressing cells, all fusion constructs were associated with cellular membranes. gag-beta-gal proteins which were capable of release from cells demonstrated a two component immunofluorescence staining pattern consisting of a circle of fluorescence around the nucleus and a punctate pattern of staining throughout the remainder of the cell. Interestingly, fusions within the matrix protein were trapped intracellularly and yielded distinct perinuclear staining patterns, possibly localizing to the rough endoplasmic reticulum and/or Golgi. This observation suggests that Moloney murine leukemia virus gag proteins travel to the plasma membrane by vesicular transport associated with the cytoplasmic face of intracellular vesicles. PMID- 2109102 TI - Ultrastructural changes during lysis of L929 target cells by class II-restricted influenza virus-specific murine cytotoxic T-lymphocyte clones. AB - Lysis of virus-infected L929 target cells transfected with the H-2 class II IAk gene by class II-restricted influenza virus-specific murine cytotoxic T lymphocyte (CTL) clones was studied by electron microscopy and compared with lysis of L929 cells by class I-restricted CTL clones. T lymphocytes predominantly approached the basal surface of target cells grown on a plastic dish and also approached uninfected L929 target cells, although virus maturation exhibited no polarity with respect to the cell surface site. After incubation for 30 min, the target cell nuclei began to change: chromatin became irregularly redistributed and aggregated, and the nuclei appeared swollen. Later, electron-dense and -light areas of nuclei became segregated, and the cytoplasm became disorganized with many vacuoles. The ultrastructural changes of target cells during lysis by class I- and class II-restricted CTL clones appeared to be similar. These findings and other cytotoxicity data of class I and class II CTLs are discussed. PMID- 2109103 TI - Morphologic characteristics of adsorbed human plasma proteins on vascular grafts and biomaterials. AB - Protein adsorption on the surfaces of clinically significant prosthetic vascular graft materials from human whole blood was independent of plasma concentration as determined morphologically by use of immunogold labels. Some proteins, such as fibrinogen, adsorbed in a multilayer pattern on expanded polytetrafluoroethylene and had a preference for particular surface features of the polymer. Other proteins, such as Hageman factor (factor XII), showed diffuse adsorption patterns. Physiologically significant proteins that have not been well studied, such as immunoglobulin G and factor VIII, adsorbed readily to the surface of expanded polytetrafluoroethylene. This finding may be significant since adsorbed proteins may activate coagulation mechanisms and immunologic responses, including platelet and monocyte adhesion and activation. Any human blood protein for which an antibody has been developed can be studied by use of this technique. PMID- 2109104 TI - Molecular biology research offers new weapons against cancer. PMID- 2109105 TI - The aging of America. Impact on health care costs. AB - The rapid growth of the oldest age groups will have a major impact on future health care costs. We use current US Census Bureau projections for the growth of our oldest age groups to project future costs for Medicare, nursing homes, dementia, and hip fractures. Without major changes in the health of our older population, these health care costs will escalate enormously, in large part as a result of the projected growth of the "oldest old," those aged 85 years and above. Medicare costs for the oldest old may increase sixfold by the year 2040 (in constant 1987 dollars). It is unlikely that these projected increases in health care costs will be restrained solely by cost-containment strategies. Successful containment of these health care costs will be related to our ability to prevent and/or cure those age-dependent diseases and disorders that will produce the greatest needs for long-term care. PMID- 2109106 TI - The sunny side of aging. PMID- 2109107 TI - A technique for intravenous nutrition in the newborn rabbit. AB - A technique and nutritional regimen for intravenous feeding of neonatal rabbits is described. Central venous nutrition of 40- to 60-g newborn rabbits was accomplished in a modified infant incubator using a specially constructed catheter and light-weight harness to provide nutrients by central vein for periods up to 7 days. Throughout the infusion period the newborn rabbits appeared healthy and evidenced increasing activity with age. The pups grew an average of 6.3 g/day, while receiving an intake of 150 to 200 kcal/kg/day. This model appears capable of being utilized to provide information on neonatal growth and metabolism in response to parenteral nutrition. PMID- 2109108 TI - Flexible nasogastric feeding tube tip malposition immediately after placement. PMID- 2109109 TI - Growth response to enteral feeding by children with cerebral palsy. AB - This study evaluated the growth of 51 children with cerebral palsy after the initiation of enteral tube feedings. The children were divided into three groups according to how soon after their central nervous system (CNS) insult they were started on enteral feedings. Group 1 consisted of 14 children who were within a year of their CNS insult; they were underweight for age, but had normal length as well as weight for length. Within 6 months of initiating enteral tube feedings, most children in this group had normalized their weights. Group 2 consisted of 27 children who were within 8 years of their CNS insult; they were stunted and were underweight for both their age and their length. Within 6 months of initiating enteral feeds, the group increased both weight and weight for length to near normal, but their gains in length reached a plateau at 90% of ideal for age. Group 3 consisted of 10 children who were more than 8 years after their CNS insult. This group was severely malnourished but had some improvement in their weight for age and for length but, length for age showed no significant change. We conclude that the earlier adequate nutritional management of children with severe cerebral palsy is initiated, the more readily the nutritional deficits will reverse. PMID- 2109110 TI - Thrombosis of the superior vena cava due to a central catheter for total parenteral nutrition. AB - Total parenteral nutrition (TPN) today is a fundamental procedure in the treatment of critically ill patients, especially if they have serious gastrointestinal diseases. However, use of the central venous catheter is connected with a very important morbidity. At the "Istituto di Patologia Chirurgica" and at the "Intensive Care Unit" of the University of Ferrara, we analyzed 59 cases of deaths from different diseases, on whom a postmortem examination had been performed. Twenty-seven patients had had no central venous catheter: none of them presented thrombosis of the central veins. Thirty-two patients had had a central venous catheter for TPN: five of them presented thrombosis of the central veins at the post-mortem examination. Except for one case who had thrombosis connected with a carcinoma of the right main bronchus, four cases (12.9%) presented thrombosis due to the central venous catheter. The subclavian vein seems to be more commonly connected with thrombosis than the jugular vein. PMID- 2109112 TI - Sepsis during total parenteral nutrition. PMID- 2109111 TI - Effects of formula composition on hepatic and intestinal drug metabolism during enteral nutrition. AB - Significant compositional differences in protein and lipid content are present in currently available enteral nutrition preparations. Since variations in dietary protein and/or lipid have previously been shown to produce alterations in liver and gut drug metabolism, effects of five commonly used enteral nutrition regimens on several drug metabolic parameters were assessed in rats. Study formulations included: 1) Vivonex: low protein -no lipid; 2) High Protein Vivonex: normal protein -no lipid; 3) Vital: normal protein -normal lipid; 4) Sustacal: high protein -high lipid; 5) Isocal: normal protein -high lipid. Hepatic and intestinal microsomes were prepared after a continuous 7-day intragastric infusion of one of the formulations, and measurements of cytochrome P-450 content and assays of drug metabolizing activity were performed. No differences in intestinal microsomal cytochrome P-450 content or meperidine demethylase activity were seen among the various alimentation groups. However, significantly decreased amounts of cytochrome P-450 and reduced meperidine demethylase and pentobarbital hydroxylase activity were present in hepatic microsomes of animals receiving the lipid-poor Vivonex and High Nitrogen Vivonex preparations compared to the other alimentation groups. These data suggest that the composition of enteral nutrition formulations may significantly impact on hepatic function and specifically that the presence of lipid in such preparations may be important for maintaining normal levels of hepatic drug metabolism. PMID- 2109113 TI - Fatty acid composition of adipocyte membrane phospholipids and stored triglycerides in infants receiving total parenteral nutrition. AB - Fatty acid (FA) composition of membrane phospholipids (PL) and stored triglycerides (TG) from adipose tissue was studied in eight infants aged 1 to 4 months receiving total parenteral nutrition (TPN) since birth. During this period, essential fatty acid (EFA) intake consisted exclusively of soybean oil emulsion administered by intravenous route (Intralipid 20%) representing 301 +/- 88 mg/kg/24 hr of linoleic acid and 58 +/- 18 mg/kg/24 hr of alpha-linolenic acid, or 2.3 +/- 0.6% and 0.4 +/- 0.1%, respectively, of total energy intake. The results were compared with those of eight control infants of the same age receiving orally a normal milk diet with an intake of 660 +/- 260 mg/kg/24 hr of linoleic acid and 101 +/- 35 mg/kg/24 hr of alpha-linolenic acid, or 4.5 +/- 0.7% and 0.7 +/- 0.3%, respectively, of total energy intake. Although their EFA intake was significantly lower (p less than 0.01) and administered only parenterally, after 1 to 4 months the infants receiving TPN still had a membrane phospholipid FA pattern of adipose tissue which was not significantly different from that of normal children of the same age. In stored adipocyte TG, the percentage of linoleic acid was significantly lower (p less than 0.01) in infants receiving TPN. This is probably of nutritional importance as at this stage of life the child builds up its stores of EFA. The proportion of the other fatty acids in adipocyte TG was not significantly modified. PMID- 2109114 TI - Comparison of low, medium, and high carbohydrate formulas for nighttime enteral feedings in cystic fibrosis patients. AB - This study examined whether the increase in CO2 production (VCO2) and ventilatory demands by carbohydrate loading with different formulas during nighttime enteral feedings could be detrimental in young adult cystic fibrosis patients with moderate to advanced lung disease. Ten patients age 17 to 24 (mean 21.4 years) received 1000 kcal/M2 of a low (Pulmocare), medium (Ensure Plus), and high (Vivonex HN) carbohydrate formula in random order. Eight patients had severe, and two moderate obstructive pulmonary disease; nine used nighttime oxygen therapy. Basal energy expenditure (BEE) without feedings averaged 120% of that predicted by the Harris-Benedict equation. The metabolic expenditure by indirect calorimetry during nighttime feedings was 25 to 36% greater than the BEE. Oxygen consumption (VO2) increased 21 to 27% during nighttime feedings with no difference between formulas. VCO2 increased 29% for Pulmocare, 46% with Ensure Plus, and 53% with Vivonex HN. The increase in VCO2 with Pulmocare was significantly less than Ensure Plus (p less than 0.05) and Vivonex HN (p less than 0.005). The respiratory quotient (RQ) (VCO2-/VO2) for Pulmocare (0.88) was the same as the BEE, but increased with Ensure Plus (1.00), and Vivonex HN (1.08). The 41% increase in minute ventilation with Vivonex HN was greater than the 25 to 28% increase observed for Pulmocare and Ensure Plus (p less than 0.05). Transcutaneous oxygen saturation fell no more than 2% with all formulas. PCO2 changed +/- 5 torr during enteral feedings with similar changes in any patient with all formulas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109115 TI - Reliability of the twenty-four-hour nitrogen balance in parenterally fed newborn infants. AB - The reliability of shorter nitrogen balance determinations was evaluated in order to facilitate the nutritional assessment of parenterally fed infants. The intraindividual day-to-day variations of nitrogen intake, excretion, and retention were analyzed in 23 parenterally fed newborn infants (birth weight: 785 2630 g). Nitrogen retentions measured over 3 consecutive days were highly correlated (r = 0.90-0.96), and the reliability for a single 24-hr collection was estimated by r1 = 0.93. Nitrogen balance data obtained over a 24-hr period are reliable for the purpose of clinical investigations, provided the nutrient intake is constant. PMID- 2109116 TI - Evaluation of the endotoxin retention capabilities of inline intravenous filters. AB - The capabilities of inline filters to retain bacteria and endotoxin were examined during simulated extended infusions for up to 168 hr. The tested inline filters were the ELD96 (Pall Biomedical Corp) and the IVEX 2 (Millipore Corp). Approximately 1 x 10(8) total cells of Escherichia coli B. were challenged to the upstream site of the filter. The test solution of 5% dextrose in water, 0.9% saline, Paremental A (A basic solution for total parenteral nutrition (TPN), a TPN solution in use in our clinic were infused continuously up to 168 hr and flow rate was maintained at 83 ml/hr. The effluents were analyzed using the Limulus Amebocyte Lysate (LAL) test to detect endotoxin and also passage of the challenged bacteria was tested at 24-hr intervals over 168 hr. The results were as follows: (1) The viability control culture showed the presence of viable bacteria throughout the 168-hr period of the experiment. (2) During the experiments, all filters produced sterile effluents. (3) LAL assay indicated that only the effluents from the ELD96 contained no detectable endotoxin for 168 hr. PMID- 2109117 TI - Nutritional support of the dysphagic patient: methods, risks, and complications of therapy. AB - The indications, methods, and complications of nutritional support of 90 patients admitted with a primary complaint of dysphagia were reviewed. Patients were divided into two groups based on etiology of dysphagia (central neurologic vs local mechanical dysfunction). All patients on admission exhibited marked malnutrition with an average weight loss of 12 +/- 9.8% body weight, serum transferrin 165 +/- 60.1 mg/dl, and albumin 3.2 +/- 0.85 mg/dl. All patients were placed on either enteral (63%) or parenteral (37%) nutrition. Twenty-seven percent of all patients suffered a complication of nutritional therapy. Patients with nasoenteric tubes had a 10% complication incidence (aspiration or endotracheal placement of tube) resulting in a 30% mortality rate; significantly higher (p less than 0.05) than seen with other modalities. Any form of upper enteric feeding (nasoenteric or gastrostomy) was associated with significantly increased (p less than 0.01) risk of aspiration pneumonia. It is concluded that patients admitted to hospital with dysphagia as the major complaint suffer from severe malnutrition, and that upper gastrointestinal intubation should not be employed for feeding until the dysphagia has resolved. PMID- 2109118 TI - Small bowel resection-associated urinary calcium loss in rats on long-term total parenteral nutrition. AB - This study was designed to study the effects of small bowel resection on daily urinary excretion patterns, plasma and bone levels of magnesium, phosphorus and calcium in rats on long-term total parenteral nutrition (TPN). Male Sprague Dawley rats weighing 300 to 350 g were randomly divided into two groups with six rats in each group. Control consists of rats whose small intestines were transected but anastomosed. Resected rats had 70% of their small intestine removed. After intestinal resection and transection, rats were infused with a balanced TPN solution for 17 days. Resected rats excreted significantly more calcium than transected rats during the first 10 days of TPN infusion. Peak excretion occurred between day 3 and 4 followed by a trend toward a slightly higher than normal level of calcium excretion between days 10 and 17. Urinary losses of phosphorus and magnesium were not influenced by bowel resection. Plasma and tibia calcium, phosphorus and magnesium levels were not altered. The effects of small bowel resection on urinary calcium loss is specific and our data demonstrate the involvement of gut in regulating urinary calcium excretion and suggest that gut may play a significant role in TPN induced metabolic bone disease. PMID- 2109119 TI - Effect of heat processing and storage on protein quality and lysine bioavailability of a commercial enteral product. AB - Several rat bioassays were conducted to evaluate protein quality and lysine (LYS) bioavailability (BIO) of Osmolite HN, a commercial enteral product, as affected by the severity of heat processing during sterilization and by storage of the products for 1 year. Without amino acid supplementation, the protein quality of Osmolite HN, as determined by protein efficiency ratio (PER), was lower than that of casein, regardless of heat treatment. With addition of the limiting amino acid, cystine, the PER of Osmolite HN was equivalent to that of cystine-fortified casein. Storage of the product for 1 year had no effect (p greater than 0.05) on PER, even though the products had darkened in color. Slope-ratio regression analysis (weight gain regressed on supplemental LYS intake) yielded a LYS BIO estimate of 94.4% for the Osmolite HN control relative to crystalline LYS. Partitioning weight gain into that resulting from LYS consumed in the basal diet and that resulting from the LYS supplement per se provided more accurate estimates of LYS BIO. This method estimated LYS BIO at 100% for the Osmolite HN products, regardless of heat treatment. With storage, LYS BIO decreased 11-12% in all of the Osmolite HN products. The decreased LYS BIO is of minimal nutritional significance in that overall protein quality of the products was not affected by storage. This is likely due to the fact that there is a plethora of lysine in Osmolite HN such that LYS is not a protein-quality limiting factor. PMID- 2109120 TI - Vitamin A sorption to polyvinyl and polyolefin intravenous tubing. AB - The loss of vitamin A to plastic infusion tubing from a total parenteral nutrition solution was studied using an in vitro infusion system and HPLC quantification of vitamin A. Polyolefin tubing was compared to polyvinyl chloride at varied vitamin A concentration, infusion temperature, and flow rate. Significantly enhanced recovery of vitamin A was found with the polyolefin tubing compared to that of the polyvinyl chloride under all conditions tested. After 24 hours under the varied conditions of the study, vitamin A availability ranged from 47 to 87% with polyolefin and 19 to 74% with polyvinyl chloride. These differences may be expected to result in significantly greater vitamin A delivery from polyolefin compared to polyvinyl chloride tubing to patients treated in neonatal intensive care units. PMID- 2109121 TI - Comparative clearance of two new fat emulsions--Hausmann Lipid 20% and Lipovenos 20%--versus intralipid 20%. AB - Intravenous fat tolerance tests (IVFTT) were performed in 13 healthy men volunteers once a day during three consecutive days in order to compare three different fat emulsions randomly administered (Intralipid 20%, Hausmann Lipid 20%, Lipovenos 20%). The amount of fat was 0.1 g/kg of body weight injected within 32 +/- 4 sec and the lipid clearance was determined over 40 min. The fractional removal rates k for the three different emulsions of fat were 5.38 +/- 1.67, 4.95 +/- 2.15, 3.92 +/- 1.31 %/min, respectively (mean +/- SD), and the half-life time of clearance T1/2 were 14.5 +/- 5.8, 16.9 +/- 7.4, 19.2 +/- 5.2 min, respectively. The highest fat particles values were observed 5 min after the bolus and all concentrations remained within the normal range (0-3 g/liter) during the study. In addition, no adverse effects were observed throughout the IVFTT. The nonparametric analysis of variance (Friedman's test) showed no significant differences between groups, even if Lipovenos 20% tended to be cleared more slowly than Intralipid 20%. These results suggest that the three fat emulsions are similarly eliminated from the blood stream and do not result in acute intolerance. Further studies based on prolonged infusion should be carried out to determine whether the two new emulsions might be alternatively used for intravenous nutritional support. PMID- 2109122 TI - The refeeding syndrome: a review. AB - Refeeding syndrome has been used to describe those phenomena, such as severe hypophosphatemia and other metabolic complications, seen in malnourished patients receiving concentrated calories via total parenteral nutrition. The purpose of this review is to clarify and broaden this definition, as well as to make recommendations for its recognition and, more importantly, prevention. PMID- 2109123 TI - Non cardiac chest pain--current concepts. PMID- 2109124 TI - Potency disorder among Pathans. AB - In a working class industrial area of Karachi hundred consecutive Pathans presenting to a family physician with potency disorder were examined. After exclusion of those with structural or drug related conditions, a structured proforma was introduced. Their presentation, associated symptoms and background pointed to masked depression and lack of sex education. Symptoms of anxiety were noticed in 49% and depressive features in 43%. The guilt feelings were reinforced by Hakims and lay literature which stress more on masturbation (79%) and spermatorrhoea (60%) and not extra-marital intercourse (52%) or bestiality (39%). PMID- 2109125 TI - Criteria for diagnosis in pulmonary tuberculosis. AB - In a retrospective study, case records of 1061 patients treated with antituberculosis drugs were examined to assess the criteria for diagnosis in each case. Seventy six percent had sputum examined for A.F.B. and 45% had mantoux test done. Five hundred and eighty one (55%) were diagnosed on radiology alone, while 262 (25%) had positive sputum for A.F.B. Only 50 (5%) of cases had positive Mantoux in addition to positive sputum and radiological changes. Practical significance of this practice is discussed. PMID- 2109126 TI - Extracorporeal shock wave lithotripsy. PMID- 2109127 TI - Association of alpha-1 antitrypsin in cirrhosis and chronic hepatitis by immunoperoxidase (PAP) method. PMID- 2109128 TI - Haemangiopericytoma of nose and paranasal sinuses. PMID- 2109129 TI - Amoebic pericardial effusion--diagnosis suggested by ultrasonography. PMID- 2109130 TI - A visit to Digri--Tharparkar. PMID- 2109131 TI - Noise pollution in Karachi. PMID- 2109132 TI - Hepatic involvement with typhoid fever: a report of nine patients. AB - Salmonella typhi has been reported to cause hepatic involvement. We studied nine patients with positive blood cultures in order to identify characteristic features of typhoid hepatitis which may help in early diagnosis. Patients who had an illness resembling enteric fever but negative cultures for Salmonella typhi were excluded. No specific clinical features were found consistently and liver function tests were widely variable. Other biochemical abnormalities occurred due to vomiting and renal involvement. Liver biopsy showed focal hepatocellular necrosis and non specific inflammation. Although most responded to conventional antibiotics, it was generally a delayed response. It is recommended that patients with fever greater than 38.5 degrees C and liver abnormalities should undergo blood, urine, stool and/or bone marrow cultures. Liver biopsy may help to differentiate typhoid hepatitis from acute viral hepatitis. PMID- 2109133 TI - Chromosomal pattern in acute lymphoblastic leukaemia. AB - Analysis of the chromosomal changes in various neoplasia is being increasingly carried out not only to evaluate its relationship with the prognosis and biological behaviour of the tumour but also for diagnostic purposes in some cases. Leukaemias are one such group of haematological malignancies which have been most extensively studied in this regard. Karyotypic analysis with Giemsa banding technique was carried out in 35 consecutive cases of Acute Lymphoblastic Leukaemia. Eighteen cases were in children (less than 15 years age) and 17 cases were in adults. M.F. ratio was 1.8:1 FAB classification of these cases showed 31 cases of L1 type and 4 cases of L2 type including one case of T-ALL. Fifteen cases (43%) had no karyotypic abnormality, 6 cases (17%) showed pseudodiploidy, one case each having (-20 + 21), t (9:22), (+ 2-6), (-6 + 8), while two cases had 6 q-.13 cases (37%) showed hyperdiploidy with 6 cases showing trisomy 8 alone, one case (+ 8 + 21), one case trisomy 18, one case + 15(r), one case trisomy 21 plus t (9:22) and one case with trisomy 21 only. Two cases showed more complex abnormalities i.e. + 2 + 8, t (13:22) and -11 + MR + Min + Min. There was one (3%) case of hypodiploidy showing monosomy 6. The above findings are in agreement with studies carried out in other countries except t (13:22) which is rather a scarcely reported abnormality. PMID- 2109134 TI - [Blood flow in the operating field during controlled hypotension by nitroglycerin, trimetaphan and prostaglandin E1]. AB - We used the laser flowmeter to measure and compare the effect of nitroglycerin (TNG), trimetaphan (TMP) and prostaglandin E1 (PGE1) on the blood flow of operating field during hypotension induced by each drug. The study was done in 33 patients (TNG:13, TMP:13 and PGE1:7) anesthetized with modified NLA who underwent radical mastectomy. We put the probe of the laser flowmeter on the skin of the opposite breast to the operating field and measured the skin blood flow change. Measurements were made before and during hypotension induced by each drug. TMP induced hypotension decreased blood flow significantly (P less than 0.05), but TNG and PGE1 had no significant effect. Intraoperative blood losses of TNG and PGE1 group were not significantly larger than that of TMP group. From this study we conclude that TNG, TMP and PGE1 can dry the operating field and decrease intraoperative blood loss similarly. Therefore we should choose the drugs to induce hypotension considering the effect of the drug on blood flow of the important organs and each patient's complications. PMID- 2109135 TI - [A simple method of extracorporeal membrane oxygenation (ECMO)--3. The effects of pumpless ECMO (arterio-venous shunt) on arterial blood gas measured for 24 hours]. AB - In eight anesthetized mongrel dogs, the pumpless ECMO applied between the femoral artery and vein was performed under the condition of hypoventilation for 24 hours. The methods were same as the first and second reports, except the pumpless ECMO was used. The abnormal parameters in the cardiovascular and respiratory system (blood gas analysis and end expiratory gas analysis), induced by hypoventilation, recovered to almost normal ranges, by operation of the pumpless ECMO for 24 hours. The pumpless ECMO might have such advantages over ECMO with pump as the less destruction of blood cell, easy performance and simple apparatus. In conclusion, pumpless ECMO using arterio-venous shunt may be applied clinically on respiratory distress conditions. PMID- 2109136 TI - [A solitary extramedullary plasmacytoma of the nasopharynx]. AB - A 72-year-old male, complaining of epistaxis, was referred to our hospital where a physical exam revealed a tumorous mass in the nasopharynx. A subsequent immunohistopathological investigation found that the tumor mass was a plasmacytoma with IgG and a lambda chain. Electrophoresis of a serum sample revealed a normal value and there was no signs indicating a multiple myeloma on x ray surveys of the skeleton, or from bone marrow aspiration or scintigraphy. Thus the diagnosis was an extramedullary plasmacytoma and the patient received a combined treatment of chemotherapy, radiotherapy, and surgery. Since surgery, the patient has had neither a recurrence or a metastasis of the tumor for four years and three months. PMID- 2109137 TI - [A myeloma (IgG-kappa) terminating in acute myelogenous leukemia]. AB - A 71-year-old man was hospitalized in November, 1983 for a back pain and a diagnosis of multiple myeloma was made, based on the Bence Jones proteinuria, The serum M-component of a IgG-kappa type (3.3 g/dl), and plasmacytosis in the bone marrow (37%). Treatment consisted of melphalan and prednisolone. A blood count in March, 1986 revealed 6000/microliters of WBC with 30% of a blast form and 8% plasma cells, and 20,000/microliters of platelets. A bone marrow aspirate revealed that 14% were myeloblasts and 26% were plasma cells. Distinguishing the myeloblasts from the immature plasma cells in the peripheral blood proved difficult. Studies by electron microscopy and an immunological inspection of phenotypes were helpful in achieving a determination. A karyotypic analysis of the bone marrow cells indicated a hypodiploid cell population, a marker chromosome, and a karyotypic instability. These findings indicate that his multiple myeloma had undergone a leukemic change associated with acute myelogenous leukemia. PMID- 2109138 TI - [A case of B-cell non-Hodgkin's lymphoma with prominent splenomegaly and high serum titer of cold agglutinin]. AB - The case of 37-year-old male with non-Hodgkin's lymphoma with prominent splenomegaly is presented. The spleen that was removed for analysis had a weight of 2690 grams and a section inspection revealed multiple, whitish, small nodules that were disseminated throughout the entire spleen. It was microscopically demonstrated to be a B-Cell lymphoma of diffuse, medium-sized cells and an IgM.kappa Type. This case also was complicated by a high serum titer of cold agglutinin that was decreased by chemotherapy. PMID- 2109139 TI - [Incidence and clinical significance of the esophageal branches originating from the bronchial artery]. AB - The authors investigated the incidence and extent of angiographic visualization of the esophageal branches originating from the bronchial arteries. Approximately 20% of 371 patients showed considerable blood flow to the esophagus. The left bronchial artery more often gives rise to the esophageal branches. Esophageal complications have been experienced in 8 cases following bronchial artery infusion of Mitomycin C for pulmonary carcinoma. Complications tend to occur in cases showing marked opacification of the esophageal veins or in those which a lesion locates in the peripheral portion of the lung. It is imperative to pay attention to esophageal branches of the bronchial artery in interventional angiography. PMID- 2109140 TI - [A case of lateral thoracic meningocele without neurofibromatosis]. AB - A case of lateral thoracic meningocele without neurofibromatosis is reported. CT myelography revealed the mass has the communication with CSF space. So we could differentiate it from a posterior mediastinal tumor. It is important to think of the presence of lateral thoracic meningocele when any posterior mediastinal mass is detected. PMID- 2109141 TI - [A case report of esophageal intramural pseudodiverticulosis]. AB - A 76 year old man with esophageal intramural pseudodiverticulosis occurring in reflux esophagitis is presented. This unusual condition characterized by multiple small outpouchings in the esophageal wall and associated with a high incidence of benign esophageal stricture. Our case demonstrated typical radiological feature by barium swallow. PMID- 2109142 TI - Osmotic diuresis and proximal tubular lithium reabsorption in the dog. PMID- 2109143 TI - [Fatal iatrogenically-induced hyperglycemia following accidental glibenclamide ingestion]. AB - A 2 9/12 years old girl had swallowed 8 to 9 tablets Euglucon N. By concatenation of unfortunatable facts the infant died of hyperglycaemia. The findings from this case should contribute to differentiate also in medical textbooks therapeutic recommendations. PMID- 2109144 TI - Type I glycogen storage disease with vasoconstrictive pulmonary hypertension. PMID- 2109145 TI - Immunoquantification of the low abundance lysosomal enzyme N-acetylgalactosamine 4-sulphatase. AB - The low abundance lysosomal enzyme N-acetylgalactosamine 4-sulphatase (4 sulphatase) has been quantified using a microimmunopurification step and a monoclonal-based ELISA detection system. The assay is similar in principle to a two-site ELISA but uses a single monoclonal antibody against one epitope to bind 4-sulphatase in two separate assay steps. The sensitivity of this assay is sufficient to allow the quantification of 4-sulphatase in human cultured skin fibroblasts derived from normal controls and patients deficient in 4-sulphatase activity (mucopolysaccharidosis type VI or Maroteaux-Lamy syndrome). The results obtained suggest a range of mucopolysaccharidosis type VI or 4-sulphatase deficient mutants, from those expressing little or no quantifiable 4-sulphatase protein to those examples with quantifiable levels of 4-sulphatase protein which is enzymically inactive. Phenotypic variability in patients with a 4-sulphatase deficiency may therefore be partially attributed to a range of protein expressions. The method should allow the determination of 4-sulphatase specific activity in mucopolysaccharidosis type VI patients. PMID- 2109146 TI - A new case of dihydropyrimidine dehydrogenase deficiency. AB - We present the clinical and biochemical features of a boy with dihydropyrimidine dehydrogenase deficiency, which seem to underline a disease entity of developmental retardation, epilepsy and muscular hypertonia. PMID- 2109147 TI - The control of 5-hydroxytryptamine and dopamine synthesis in the brain: a theoretical approach. AB - The transport of the eight amino acids (phenylalanine, tyrosine, tryptophan, valine, leucine, isoleucine, histidine and methionine) using the large neutral amino acid transporter of the blood-brain barrier (BBB) has been calculated using published kinetic data. The fate of the amino acids has been followed from blood to interstitial space, to cell and through metabolism which included, for tyrosine and tryptophan, the hydroxylases. The system was analysed in terms of flux control coefficients. Since the summation theorem did not hold, the system clearly behaved as a non-homogeneous system. At physiological levels of these eight amino acids, the largest contribution to the control of the flux of tyrosine is given by the hydroxylase step, followed by the diffusional component of the transport across the BBB. For tryptophan it is the hydroxylase step, followed by the carrier-mediated transport across the BBB. For the other amino acids it is the metabolism, followed by the diffusional component of the BBB transport. These parameters for tyrosine and tryptophan were determined at increased levels of blood phenylalanine, tyrosine or histidine. The flux through tryptophan hydroxylase can be affected by high blood levels of tyrosine and histidine to values also observed in hyperphenylalaninaemia. Since hypertyrosinaemia (type II) and hyperhistidinaemia are not associated with mental retardation, it is concluded that interference with transport across the BBB of tyrosine and tryptophan, as well as the flux through tryptophan hydroxylase leading to the synthesis of 5-hydroxytryptamine, do not contribute to the cause of permanent brain dysfunction in hyperphenylalaninaemia. It can be calculated that addition of tyrosine to the diet to raise the blood tyrosine level in phenylketonuria patients may have a beneficial effect for the synthesis of neurotransmitters derived from tyrosine. PMID- 2109149 TI - A comparison of [9,10-3H]palmitic and [9,10-3H]myristic acids for the detection of defects of fatty acid oxidation in intact cultured fibroblasts. AB - The production of tritiated water from [9,10-3H]myristic acid can be used as a screening assay for the detection of medium-chain acyl-CoA dehydrogenase deficiency, multiple acyl-CoA dehydrogenation defects (glutaric aciduria type 2 and ethylmalonic-adipic aciduria types), and some types of hydroxydicarboxylic aciduria. Comparison with the release of tritiated water from [9,10-3H]palmitic acid may give an indication of the chain-length specificity of the metabolic defect. In a case of ethylmalonic-adipic aciduria such a prediction has been confirmed by examination of accumulated intermediates in the affected fibroblasts. PMID- 2109150 TI - Carnitine deficiency with cardiomyopathy presenting as neonatal hydrops: successful response to carnitine therapy. AB - A small-for-date infant presented at birth with severe non-immune hydrops, cardiac failure, metabolic acidosis and hypoglycaemia. Ultrasonography disclosed a cardiomyopathy. Initial therapy consisting of artificial ventilation, inotropes and diuretics resulted in partial disappearance of oedema without significant improvement in cardiac function. Episodes of hypoglycaemia recurred despite continuous glucose infusions. Total serum carnitine from cord blood was 1.65 nmoles/ml and was undetectable on day 20. Oral DL-carnitine supplements resulted in normoglycaemia, dramatic improvement in cardiac function and restoration of serum carnitine levels to normal values. The infant was thereafter maintained on carnitine therapy. Follow-up over 1 year showed moderate growth retardation and normal developmental milestones. In order to account for such a severe neonatal presentation of carnitine deficiency, a combination of defective pre- and postnatal carnitine supply with an inborn error of carnitine handling is considered. The present case illustrates the need for evaluation of carnitine status in fetuses and neonates presenting with hydrops associated with cardiac failure. PMID- 2109148 TI - The inborn errors of peroxisomal beta-oxidation: a review. AB - In recent years a growing number of inherited diseases in man have been recognized in which there is an impairment in peroxisomal beta-oxidation. In some diseases this is due to the (virtual) absence of peroxisomes leading to a generalized loss of peroxisomal functions including peroxisomal beta-oxidation. In most inborn errors of peroxisomal beta-oxidation, however, peroxisomes are normally present and the impairment in peroxisomal beta-oxidation is due to the single or multiple loss of peroxisomal beta-oxidation enzyme activities. In all these disorders there is accumulation of very-long-chain fatty acids in plasma, which allows biochemical diagnosis of patients affected by an inborn error of peroxisomal beta-oxidation to be done via gas-chromatographic analysis of plasma very-long-chain fatty acids. Subsequent enzymic and immunological investigations are required to identify the precise enzymic defects in these patients. In all inborn errors of peroxisomal beta-oxidation known today there are multiple abnormalities, especially neurological with death usually occurring in the first decade of life. Prenatal diagnosis of these disorders has recently become possible. PMID- 2109151 TI - Comparison of patients with complete and partial biotinidase deficiency: biochemical studies. AB - Seventeen partially biotinidase-deficient patients detected by neonatal screening or family studies were compared with four patients with classical biotinidase deficiency. Using a sensitive HPLC method for biotinidase in plasma (substrate: biocytin) the patients could be divided into two groups: one with residual biotinidase activity, and the second with undetectable biotinidase activity (0 activity). Biocytin excretion, characteristically elevated in 0-activity patients, decreased rapidly with increasing residual biotinidase activity and was almost normal when residual activity exceeded 2-3% of mean normal. In one patient with classical disease (0-activity) biotin deficiency, typical organic aciduria and multiple carboxylase deficiency were found as early as at the second week of life. In contrast, 13 infants with residual activities from 1.2% to 23% had no remarkable clinical or biochemical abnormalities. However, in three 5-, 14- and 15-year-old healthy siblings with residual biotinidase activities between 2.3% and 4.2%, biotin deficiency was proven by decreased activities of the mitochondrial carboxylases in lymphocytes (30-57% of mean normal) and, in the older siblings, also by subnormal plasma biotin concentrations. In biotinidase deficiency, biotin depletion presumably occurs earlier in the brain than in other tissues and may thus first affect the central nervous system. For this reason and because of discrete biochemical abnormalities found in a patient with residual biotinidase activity of 8%, we suggest that at least all patients with residual activities below 10% should be treated with biotin. PMID- 2109152 TI - Results of newborn screening for galactose metabolic disorders. AB - A screening strategy has been used which uses the Paigen and Beutler methods for the determination of galactose and galactose-1-phosphate. A blood spot test for epimerase has also been developed. In the last 10 years, 265,019 samples from newborns have been tested by these methods. Among the 154 screening positives, we have detected seven cases of epimerase-deficient galactosaemia (Type III), seven cases of Duarte/galactosaemia heterozygotes, 48 cases of other various types of heterozygotes, four cases of persistent hypergalactosaemia, three cases of hepatitis and one case of congenital atresia of the bile duct. These results indicate that our screening system has effectively detected the infants with galactose metabolic disorders. PMID- 2109153 TI - Time-courses of the appearance/disappearance of nuclear androgen + receptor complexes in the brain and adenohypophysis following testosterone administration/withdrawal to castrated male rats: relationships with gonadotropin secretion. AB - We characterized the temporal dynamics of brain and pituitary cell nuclear androgen receptor binding and serum androgen and gonadotropin levels associated with the implantation and removal of testosterone (T)-filled Silastic capsules into performed s.c. flank pouches of castrated, awake male rats. These capsules produced serum T levels in the physiologic range. The number of cell nuclear androgen + receptor complexes, as measured in an exchange assay using [3H]R1881, increased 15-fold at 0.5 h after capsule insertion in the HPAS (combined hypothalamus, preoptic area, amygdala and septum) and anterior pituitary gland, but then showed a second progressive rise within the next 8 h. This pattern suggests that T exerts an initial action in the tissues to alter the affinity and/or number of available androgen receptors. There was a lag time of 2-4 h to the first indication of negative feedback suppression of LH secretion. Serum LH levels declined only slightly at 4 h after capsule insertion but continued to fall thereafter, reaching undetectable values by 24 h. In contrast, serum FSH levels declined only slightly after 24 h of T exposure. After removal of the T capsules, serum T levels declined to castrate values within 2 h at which time the level of androgen + receptor complexes had fallen to 60% in the brain and pituitary. Serum LH and FSH concentrations were unchanged at 2 h after capsule removal, but rose significantly within the next 2 h. The data indicate that the occupation of androgen receptors rapidly changes in response to variations in circulating T in a fashion that implicates their involvement in the expression of this steroid's negative feedback actions on gonadotropin secretion. PMID- 2109154 TI - Effects of steroid implants on the prepubertal increase in circulating gonadotropins and sexual receptivity in the female rabbit. AB - The pubertal increase in gonadotropins in the female rabbit was inhibited 14-42 fold with Silastic implants of progesterone (P4) testosterone propionate (TP), estradiol benzoate (EB) or P4/EB placed subcutaneously on Day 24 of life. Rabbits with empty implants showed the normal prepubertal increase in circulating gonadotropins. By contrast, rabbits with implants of P4 only, had a 2-fold decrease in LH secretion when peak areas were compared. However, FSH secretion though slightly depressed was not significantly different from controls. The prepubertal increase in circulating gonadotropins was completely suppressed by implants of EB, TP and combined P4/EB. At 115-days-of-age, sexual receptivity and mating were absent in EB-treated animals and significantly suppressed in P4 treated ones when compared to controls, all of which mated. Mating was not completely inhibited in TP and combined P4/EB animals. Corpora lutea were found in all rabbits that mated. In the sexually non-receptive does, vaginal stimulation induced an LH surge in 2 of 15 animals. Ovarian weights and follicular development were significantly suppressed in rabbits with EB implants. Ovarian estradiol content was significantly increased in P4- and TP-treated rabbits. Maximum specific binding for [3H]naloxone was suppressed in the hypothalami of P4-treated rabbits. These results suggest that the prepubertal increase in circulating gonadotropins may have an essential role in the control of sexual maturation in the female rabbit. PMID- 2109156 TI - Tumor necrosis factor alpha and interferon gamma inhibit proliferation and alkaline phosphatase activity of human osteoblastic SaOS-2 cell line. AB - Tumor necrosis factor (TNF) alpha and TNF beta both inhibited proliferation of cultured human osteoblastic SaOS-2 cells. TNF alpha also inhibited alkaline phosphatase (ALP) activity in the cells. The TNF alpha-induced inhibition of proliferation and ALP activity was further potentiated by interferon (IFN) gamma. These findings indicate that human SaOS-2 cells, fulfilling several criteria for osteoblasts, respond to TNF alpha and IFN gamma, resulting in decceleration of their maturation. PMID- 2109155 TI - Characterization of cytosolic glucocorticoid receptor of fetal rat epiphyseal chondrocytes. AB - The cytosolic glucocorticoid receptor of 21st gestational day rat epiphyseal chondrocytes has been evaluated. The receptor, a single class of glucocorticoid binding component approached saturation, utilizing [3H]triamcinolone acetonide ([3H]TA) as the radiolabeled ligand, at approximately 1.8-2.0 x 10(-8) M. The dissociation constant (Kd) reflected high-affinity binding, equaling 4.0 +/- 1.43 x 10(-9) M (n = 7) for [3H]TA. The concentration of receptor estimated from Scatchard analysis was approximately 250 fmol/mg cytosolic protein and when calculated on a sites/cell basis equalled 5800 sites/cell. The relative binding affinities of steroid for receptor were found to be triamcinolone acetonide greater than corticosterone greater than hydrocortisone greater than progesterone greater than medroxyprogesterone acetate much greater than 17 alpha hydroxyprogesterone much greater than testosterone greater than 17 beta estradiol. Cytosolic preparations activated in vitro by warming (25 degrees C for 20 min) were shown to exhibit an increased affinity for DNA-cellulose. 46% of the total specifically bound activated ligand-receptor complex was bound to DNA cellulose. Cytosol maintained at 0-4 degrees C in the presence of 10 mM molybdate or activated in vitro in the presence of molybdate, bound to DNA-cellulose at 8 and 10% respectively. DEAE-Sephadex elution profiles of the nonactivated receptor were indicative of a single binding moiety which eluted from the columns at 0.4 M KCl. Elution profiles of activated receptor were suggestive of an activation induced receptor lability. The 0.4 M KCl peak was diminished, while a concomitant increase in the 0.2 M KCl peak was only modestly discernible. Evaluation of endogenous proteolytic activity in chondrocyte cytosol using [methyl-14C]casein as substrate show a temperature-dependent proteolytic activity with a pH optimum of 5.9-6.65. The proteolytic activity was susceptible to heat inactivation and was inhibitable, by 20 mM EDTA. The sedimentation coefficient of the nonactivated receptor was 9.3s (n = 6) on sucrose density gradients and exhibited steroid specificity and a resistance to activation induced molecular alterations when incubated in the presence of 10 mM molybdate. Receptor activation in vitro, in the absence of molybdate induced an increased receptor susceptibility to proteolytic attack and/or enhanced ligand receptor dissociation as evidenced by a diminution of the 9.3s binding form without a concomitant increase in 5s or 3s receptor fragments. PMID- 2109158 TI - Changes in protein turnover after heat shock are related to accumulation of abnormal proteins in aging Drosophila melanogaster. AB - Adult Drosophila melanogaster kept at 24 degrees C show a progressive decline in the synthesis and degradation of proteins with age. After exposure of young, 7-10 days old flies to 20 min of heat shock at 37 degrees C, the incorporation of [35S]-methionine into trichloroacetic acid precipitable proteins decreases to more than 60% of that observed in non-stressed flies. This decrease is also accompanied by a lower protein degradation rate. In contrast, the same stress in old, 49 days old insects results in a 3-fold increase in protein synthesis as compared to either non-heat shocked senescent flies or to young heat-shocked flies. The older flies also have faster protein turnover than unshocked controls. An effect similar to that observed in senescent Drosophila also occurs in young flies that have been fed canavanine, an arginine analogue, before and during heat shock. These results suggest that an age dependent accumulation of abnormal proteins may be responsible for the changes in protein turnover observed in the heat-shocked old flies. PMID- 2109157 TI - Closely related glycosylation patterns of recombinant human IL-2 expressed in a CHO cell line and natural IL-2. AB - We report here the study of the glycosylation pattern of human recombinant (r) IL2 expressed in a Chinese hamster ovary (CHO) cell line. The human rIL2 secreted by this high-producing recombinant CHO cell line was metabolically radiolabelled with [35S]-methionine, or with [3H]-glucosamine and [3H]-galactose, purified to homogeneity, and then characterized. The electrophoretic analysis of the [35S] methionine-labelled proteins present in the culture medium of the CHO cell line showed that the rIL2 represents approximately 12% of the total secreted proteins. Furthermore, pulse-chase experiments showed that the glycosylated rIL2 is synthesized and secreted within 30 min. The point of attachment and the structure of the carbohydrate moiety of the rIL2 was determined by: amino-terminal sequencing and fingerprint analysis of the 3H-labelled rIL2, mass spectroscopy of the amino-terminal tryptic octapeptide, and carbohydrate analysis after enzymatic (Vibrio cholerae neuraminidase and Aspergillus oryzae beta-galactosidase) or sulfuric acid hydrolysis. The results indicate that the recombinant protein possesses a sugar moiety O-linked to the threonine residue at position 3 of the polypeptide chain, and that sialic acid, galactose and N-acetyl galactosamine are components of this carbohydrate moiety. Taken together these results suggest that the recombinant molecule is identical to natural IL2. PMID- 2109159 TI - [Antimicrobial sensitivity, auxotype, serotype and plasmid analysis of 75 strains of Neisseria gonorrhoeae isolated in Barcelona]. PMID- 2109160 TI - [Non-A, non-B hepatitis in plasma donors. Apropos of 3 cases]. PMID- 2109161 TI - [Primary resistance to antitubercular drugs]. PMID- 2109162 TI - [Effects of omeprazole on digestive functions other than acid secretion]. PMID- 2109163 TI - [Pure red cell aplasia and neutropenia associated with chronic monoclonal T lymphocytosis]. AB - We report a patient with nonregenerative anemia and neutropenia associated with an increment of circulating large granular lymphocytes (LGL). The anemia was secondary to the absence of erythroid precursors in the bone marrow or pure red blood cell aplasia associated with moderate lymphoid infiltration by LGL. Myeloid (CFU-GM) or erythroid (CFU-E, BFU-E) precursors were not detected by bone marrow culture. A high number of T colonies was found. The lymphoid population had a cytotoxic/suppressor phenotype (CD2+, CD4-, CD8+). Virologic studies (including search for HTLV1) were carried out with negative results. A clonal origin was demonstrated by DNA analysis with probes of those genes encoding T receptor (TRc). After cytostatic therapy with cyclophosphamide and low doses of prednisone a clinical and laboratory remission was achieved. We review the literature, with a discussion of the clinical, phenotypic and molecular features of this disease as well as its response to therapy. PMID- 2109164 TI - Evaluation of in vivo [corrected] biological activity of new agmatine analogs of growth hormone-releasing hormone (GH-RH) AB - The effects of agmatine analogs of growth hormone releasing hormone (GH-RH) were compared to GH-RH(1-29)-NH2 after intravenous (iv) and subcutaneous (sc) administration to pentobarbital-anesthetized male rats. After the iv injection, the analogs [desNH2-Tyr1,Ala15,Nle27] GH-RH(1-28)Agm (MZ-2-51); [desNH2-Tyr1,D Lys12,Ala15,Nle27] GH-RH(1-28)Agm (MZ-2-57); [desNH2-Tyr1,Ala15,D-Lys21,Nle27] GH RH(1-28)Agm (MZ-2-75) and [desNH2-Tyr1, D-Lys12,21, Ala15, Nle27] GH-RH(1-28)Agm (MZ-2-87) showed a potency equivalent to 4.4, 1.9, 1.07 and 1.03 times that of GH RH (1-29)-NH2, respectively, at 5 min and 5.6, 1.8, 1.9 and 1.8 times higher, respectively, at 15 min. After sc administration, analogs MZ-2-51, MZ-2-57 and MZ 2-75 showed to be 34.3, 14.3 and 10.5 times more potent than the parent hormone at 15 min and 179.1, 88.9 and 45.0 times more active, respectively, at 30 min. In addition, MZ-2-51 had prolonged GH-releasing activity as compared to the standard. We also compared the activity of MZ-2-51 and MZ-2-57 with their homologous L-Arg and D-Arg analogs [desNH2-Tyr1,Ala15,Nle27] GH-RH(1-29)-NH2 (MZ 2-117), [des-NH2Tyr1,D-Lys12, Ala15, Nle27] GH-RH(1-29)NH2 (MZ-2-123) and [desNH2 Tyr1,D-Lys12,Ala15, Nle27,D-Arg29] GH-RH(1-29)NH2 (MZ-2-135) after intramuscular (im) injection. MZ-2-51 induced a somewhat greater GH release than MZ-2-117 at 15 min, both responses being larger than the controls (p less than 0.01) at 15 and 30 min. MZ-2-57, MZ-2-123 and MZ-2-135 given i.m. were able to stimulate GH release only at 15 minutes (p less than 0.05). Animals injected i.m. with MZ-2 51, but not with MZ-2-117, showed GH levels significantly higher than the control group (p less than 0.05) at 60 min. GH-RH(1-29)NH2 had low activity intramuscularly when tested at a dose of 2.5 micrograms. No toxic effects were observed after the iv administration of 1 mg/kg of Agm GH-RH analogs. These results indicate that our Agm analogs are active iv, sc and im and that the substitutions made in these compounds produce increased and prolonged GH releasing activity. These analogs, especially MZ-2-51, should be useful for clinical and veterinary purposes. PMID- 2109166 TI - Morphology, biometry and taxonomic position of two peritrich ciliate Protozoa found in activated sludge. AB - The morphology of two sessile peritrich species taken from a plant for the processing of activated sludge is described. One of these species, having a non contractile, branched peduncle, belongs to the genus, Heteropolaria, and the other having a single, contractile stalk, is a member of the genus Vorticella. A statistical and biometric study is made of their morphological characteristics, and the taxonomic position of both ciliates is discussed. PMID- 2109165 TI - Arteriovenous differences across human adipose and forearm tissues after overnight fast. AB - Measurements of arteriovenous differences across subcutaneous abdominal tissue (mainly adipose) and deep forearm tissue (mainly muscle) were made on 25 occasions in normal subjects after an overnight fast. Adipose tissue was shown to be strongly lipolytic (releasing nonesterified fatty acids and glycerol), to clear circulating triacylglycerol, glucose, ketone bodies and acetate, and to produce lactate. Uptake of circulating carbohydrate and ketones was sufficient to account for only 51% of the adipose tissue oxygen consumption, implying that adipose tissue utilizes fuel(s) stored within it. The mean fractional re esterification rate of fatty acids in adipose tissue was 13% to 19%. Arteriovenous differences were converted to fluxes of carbon atoms to compare the movements of different fuels. (Amino acids were not included in these calculations.) Adipose tissue after an overnight fast was a net exporter of carbon, whereas in resting muscle the uptake of carbon atoms from circulating carbohydrate and lipid fuels approximately balanced the CO2 production. Fatty acids were the main form in which carbon left adipose tissue, and the main source of carbon atoms entering the resting forearm. PMID- 2109167 TI - Intrinsic penicillin resistance in penicillinase-producing Neisseria gonorrhoeae strains. AB - The minimal inhibitory concentrations (MICs) of ampicillin for fifty strains of beta-lactamase-producing Neisseria gonorrhoeae (PPNG) isolated in Japan ranged from 1.56 to 200 micrograms/ml, and all the strains harbored a 4.5 megadalton plasmid. These strains were classified into two groups: dicloxacillin-susceptible (28%) and -resistant group (72%). A linear correlation was found in the dicloxacillin-susceptible strains between their beta-lactamase activity and the susceptibility to ampicillin, but not in the dicloxacillin-resistant strains. This suggests that the high ampicillin resistance in PPNG is due not only to acquiring the beta-lactamase producing plasmid, but also to some intrinsic resistance of the strains. To investigate a cause of the high ampicillin resistance, the beta-lactamase-producing plasmid, pTMS1, was transferred by conjugation to a penicillin-susceptible gonococcal strain as well as to its isogenic multiply antibiotic-resistant transformants, and the susceptibility of the transconjugants to ampicillin was determined. Acquisition of pTMS1 by a penicillin-susceptible strain resulted in a 32-fold increase in resistance to ampicillin, whereas the increase was 128-fold for its isogenic strains which contain some chromosomal mutations. These results suggest that reduced permeability of the outer membrane to ampicillin underlies the high ampicillin resistance of PPNG. PMID- 2109168 TI - Black-white differences in cervical cancer mortality--United States, 1980-1987. PMID- 2109169 TI - HIV-1 infection and artificial insemination with processed semen. PMID- 2109170 TI - Progress toward achieving the 1990 national objectives for the misuse of alcohol and drugs. PMID- 2109171 TI - Cigarette advertising--United States, 1988. PMID- 2109172 TI - Update: filovirus infections among persons with occupational exposure to nonhuman primates. PMID- 2109173 TI - Risk behaviors for HIV transmission among intravenous-drug users not in drug treatment--United States, 1987-1989. PMID- 2109174 TI - Laboratory services and training in support of the year 2000 national health objectives. PMID- 2109175 TI - Rocky Mountain spotted fever and human ehrlichiosis--United States, 1989. PMID- 2109176 TI - Update: evidence of filovirus infection in an animal caretaker in a research/service facility. PMID- 2109177 TI - [Clinical results of intraperitoneal hyperthermic perfusion combined with surgery in patients with peritoneal recurrence from gastric cancer]. AB - Six patients with peritoneal recurrence after radical operation for gastric cancer were treated by an intraperitoneal hyperthermic perfusion (IPHP) combined with surgery (IPHP group). Immediately after surgery, a 2-hour IPHP was performed, using a perfusate containing 10 micrograms/ml of MMC, warmed at the inflow temperature of 46.5 +/- 1.1 degree C. Within the same period of time, 5 patients with intra-abdominal recurrent gastric cancer (control group) were treated by an intraperitoneal administration of MMC 10 mg combined with surgery. These 11 patients had malignant peritoneal effusion and, although in 3 of the control group, ascitic effusion did re-accumulate rapidly soon after surgery, the 6 patients of IPHP group did not re-accumulate post-hyperthermically. The average survival duration of IPHP group is 13.6 +/- 10. 6 months, whereas that for controls is 3.0 +/- 2.1 months. Again, the survival rate for IPHP group surpassed that for controls at p = 0.012 and p = 0.008, in a generalized Wilcoxon method and Logrank method, respectively. Post-hyperthermically, hypoproteinemia and thrombocytopenia occurred transitorily. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence due to gastric cancer. PMID- 2109178 TI - The PurR mutation of Drosophila melanogaster confers resistance to purine and 2,6 diaminopurine by elevating adenosine deaminase activity. AB - Media supplemented with purine (7H-imidazo[4,5-d]pyrimidine) or the purine analogue 2,6-diaminopurine (DAP) can be employed to select several classes of purine-resistant variants from mutagenized cultures of Drosophila. One class results in elevated resistance to purine and diaminopurine which is correlated with elevated activity of the enzyme adenosine deaminase (adenosine aminohydrolase = EC 3.5.4.4). The first member of this class, Pur R, maps to position 82 +/- in the right arm of the second chromosome. The Pur R mutation causes an elevation of adenosine deaminase (ADA) enzyme activity, apparently by altering a thermolabile, ADA-specific repressor. Pur R may thus encode a negative regulator of adenosine deaminase activity similar to the ADA-binding protein found in mammalian systems. PMID- 2109179 TI - The UGA3 gene regulating the GABA catabolic pathway in Saccharomyces cerevisiae codes for a putative zinc-finger protein acting on RNA amount. AB - The UGA3 gene of Saccharomyces cerevisiae is required for 4-aminobutyric acid (GABA)-dependent induction of the UGA1, UGA2 and UGA4 genes which encode the two GABA catabolic enzymes and a GABA-specific permease, respectively. Measurements of UGA1-specific transcripts show that induction of UGA1 correlates with accumulation of its RNA and requires a functional UGA3 gene. A 2 kb DNA fragment complementing the uga3 mutation was isolated and shown to contain the UGA3 gene. The primary structure of the UGA3 encoded protein was deduced from the DNA sequence, and contains an N-terminal, cysteine-rich motif similar in sequence to regions found in other fungal regulatory proteins and which are supposed to form zinc finger structures involved in DNA binding. Mutations were identified in the UGA3 genes isolated from uninducible and constitutive uga3 alleles. One case of intragenic complementation between two uninducible uga3 mutants is reported, indicating a possible oligomeric structure for UGAe. The role of UGA3 is discussed in relation to its genetic properties and its predicted structure. PMID- 2109180 TI - The functional organization of the vestigial locus in Drosophila melanogaster. AB - Vestigial mutants are associated with imaginal disc cell death which results in the deletion of adult wing and haltere structures. The vestigial locus has previously been cloned, and mutational lesions associated with a number of vg alleles were mapped within a 19 kb DNA region defined as essential for vg function. Herein we report the identification and characterization of a developmentally regulated 3.8 kb vg transcript which is spliced from exons distributed throughout the essential interval defined above. All the characterized classical alleles have predictable effects on this transcription unit, and the severity of this effect is directly proportional to the severity of the wing phenotype. A repetitive domain within this transcription unit was identified and may serve as a tag to isolate other genes with functions related to vg. We also report an exceptional vg allele (vg83b27) that produces an extreme wing and haltere phenotype, but which defines a second vg complementation unit. This allele is associated with a 4 kb deletion entirely within a 4.5 kb vg intron as defined by the 3.8 kb transcription unit. Molecular and genetic evidence indicates that the vg83b27 mutation has a functional 3.8 kb transcription unit, thus accounting for its ability to complement classical alleles. The results indicate that sequences within a vg intron are essential for normal wing and haltere development. PMID- 2109181 TI - Immunochemical characterization of multiple forms of cytochrome P-450 in rabbit nasal microsomes and evidence for tissue-specific expression of P-450s NMa and NMb. AB - Two unique forms of cytochrome P-450 (P-450), designated NMa and NMb, were recently isolated in this laboratory from nasal microsomes of rabbits. In the present study, polyclonal antibodies to the purified nasal cytochromes were prepared. Immunochemical analysis with specific rabbit anti-NMa and sheep anti NMb antibodies indicated that P-450 isozymes identical to or having a high structural homology with NMa are present in both olfactory and respiratory mucosa, as well as in liver, but NMb was detected only in the olfactory mucosa. Neither form was detected in other tissues examined, including brain, esophageal mucosa, heart, intestinal mucosa, kidney, and lung. The specific occurrence of NMb in the olfactory mucosa was further substantiated by the detection and specific inhibition by anti-NMb of the formation of unique NMb-dependent metabolites of testosterone in olfactory microsomes but not in microsomes from liver or respiratory mucosa. Similar experiments with antibodies to previously purified rabbit hepatic P-450 isozymes indicated that not all of the hepatic cytochromes are expressed in the nasal tissues. Thus, P-450 isozymes structurally homologous to hepatic forms 2, 3a, and 4, but not 3b and 6, were found in the olfactory mucosa. On the other hand, only form 2 was detected in the respiratory mucosa. Immunoquantitation experiments revealed that NMa and NMb are the major P 450 forms in olfactory microsomes, whereas NMa and P-450 form 2 (or its homolog) constitute the major portion of the respiratory nasal microsomal P-450. The level of NMa in the liver is relatively low, accounting for less than 3% of total microsomal P-450 in this tissue. In addition, evidence is provided that NMa is the major catalyst in the dealkylation of two nasal carcinogens, hexamethylphosphoramide and phenacetin, in both olfactory and respiratory nasal microsomes. PMID- 2109182 TI - Non-steady state kinetic analysis of the regulation of adenylate cyclase by GTP binding proteins. AB - The time course of cAMP production by S49 cell membranes in the presence of forskolin and a nonhydrolyzable GTP analog can yield information about the regulation of adenylate cyclase by both the inhibitory and stimulatory GTP binding proteins (Gi and Gs). The time courses are complex and interpretation in terms of the activities of G1 and Gs requires a quantitative hypothesis. We present a general quantitative hypothesis that defines adenylate cyclase as existing in a distribution of two states, active and inactive. Gi and Gs, in their active states, alter the equilibrium of this distribution. Two distinct models are derived based on this hypothesis to accommodate two different proposed mechanisms for the action of Gi to inhibit adenylate cyclase: 1) a direct interaction between Gi and the catalytic subunit of adenylate cyclase and 2) a direct interaction between Gi and Gs. Perturbations of the regulation of adenylate cyclase by pertussis toxin and phorbol ester are simulated and interpreted using the models. The effect of pertussis toxin is quantitatively reconciled by decreases in the guanine nucleotide-independent adenylate cyclase activity and in the apparent rate of activation of Gi from 2.0/min to 0.01/min. The effect of phorbol ester is best accommodated by the model as a change in the distribution of active and inactive adenylate cyclase from 36% initially active to 47% active after phorbol ester treatment, without postulating any effect of phorbol ester on Gi or Gs. Both of these interpretations are independent of the model used. The effect of forskolin is also examined within the context of the two models. The results of this examination suggest an experimental approach for testing the models. These examples illustrate the usefulness of quantitative analysis of time course data using a model for the regulation of adenylate cyclase. We propose that, with this combined experimental and theoretical approach, one can address the relevance of hypotheses generated from experimental studies with isolated components to the molecular mechanisms of adenylate cyclase regulation in cellular membranes. PMID- 2109183 TI - 2'-Fluoro-2',3'-dideoxyarabinosyladenine: a metabolically stable analogue of the antiretroviral agent 2',3'-dideoxyadenosine. AB - In this report, we have compared the uptake, metabolism, and relevant enzymology of a novel anti-acquired immunodeficiency syndrome drug, 2'-fluoro-2',3' dideoxyarabinosyladenine (2'-F-dd-ara-A) with the corresponding properties of its parent compound 2',3'-dideoxyadenosine (2',3'-ddAdo) in three human T cell lines, MOLT-4, ATH8, and CEM. In previous communications, we have reported that the primary route of metabolism of 2',3'-ddAdo in human T lymphoblasts is catabolic, i.e., deamination to 2',3'-dideoxyinosine (2',3'-ddlno). At this point, the metabolic pathway diverges, to result in either cleavage and inactivation of 2',3'-ddlno by purine nucleoside phosphorylase or in 5'-phosphorylation by a phosphotransferase, a reaction that generates 2',3'-inosine monophosphate and ultimately the putative active metabolite 2',3'-dideoxy-ATP. Studies with kinase deficient mutant CEM lines indicate, however, that 2'-F-dd-ara-A favors a more direct anabolic route toward formation of 2'-fluoro-dideoxynucleotides, catalyzed initially by 2'-deoxycytidine kinase. In MOLT-4 cells, amounts of 2'-fluoro dideoxyarabinosyladenine di- and triphosphate formed were approximately 20-fold and 5-fold greater than the respective accumulation of 2',3'-dideoxy-ADP and 2',3'-dideoxy-ATP over the same time of exposure. This metabolic profile was supported by enzymological studies, which revealed that 2'-F-dd-ara-A is deaminated 10 times less rapidly than ddAdo and that the resulting deaminated product is resistant to hydrolysis by purine nucleoside phosphorylase. Under similar conditions, ddAdo was rapidly degraded through cleavage of its deamination product ddlno. Like ddAdo, 2'-F-dd-ara-A was found to be transported by passive diffusion and does not enter cells via the purine nucleoside transport carrier system. However, the rate of entry of 2'-F-dd-ara-A was about half that of ddAdo (9.7 pmol/10(6) cells/min for 2'-F-dd-ara-A versus 18.4 pmol/10(6) cells/min for ddAdo). This investigation, therefore, demonstrates that, under the conditions studied, 2'-F-dd-ara-A and its deamination product 2'-fluoro-2',3' dideoxyarabinosylhypoxanthine have metabolic properties that differ significantly from those of their parent compounds ddAdo and ddlno. These properties, combined with the previously reported resistance of the fluorinated nucleosides to acid degradation, make these compounds interesting candidates for further study as orally administered agents for the inhibition of human immunodeficiency virus replication in patients with acquired immunodeficiency syndrome. PMID- 2109184 TI - Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase. AB - We report that the cytoplasmic domains of the T-lymphocyte glycoproteins CD4 and CD8 alpha contain short related amino acid sequences that are involved in binding the amino-terminal domain of the intracellular tyrosine protein kinase, p56lck. Transfer of as few as six amino acid residues from the cytoplasmic domain of the CD8 alpha protein to the cytoplasmic domain of an unrelated protein conferred p56lck binding to the hybrid protein in HeLa cells. The common sequence motif shared by CD4 and CD8 alpha contains two cysteines, and mutation of either cysteine in the CD4 sequence eliminated binding of p56lck.p56lck also contains two cysteine residues within its CD4-CD8 alpha-binding domain, and both are critical to the interaction with CD4 or CD8 alpha. Because the interaction does not involve disulfide bond formation, a metal ion could stabilize the complex. PMID- 2109185 TI - Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals. AB - Egr-1 is an immediate-early response gene induced by diverse signals that initiate growth and differentiation. Its cDNA sequence predicts a protein with zinc fingers. We have generated an antiserum to the Egr-1 gene product and identified it as an 80-kilodalton short-lived protein in serum-stimulated mouse fibroblasts. The rat Egr-1 product has also been identified in nerve growth factor-induced PC12 cells. In addition, we show by cell fractionation and immunocytochemistry that the Egr-1 protein is located in the nucleus. We also demonstrate that it is phosphorylated. In vitro-generated Egr-1 protein binds with high affinity to the sequence CGCCCCCGC in a zinc-dependent manner. PMID- 2109186 TI - Initiation and processing of two kappa immunoglobulin germ line transcripts in mouse B cells. AB - The splicing patterns and sequences of two processed kappa immunoglobulin germ line mRNAs are presented. A 1.1-kilobase (kb) mRNA appeared to be derived from splicing of the previously characterized 8.4-kb germ line transcript, while a 0.8 kb mRNA was the splice product of a second 4.7-kb germ line transcript that initiated 50 base pairs upstream of J kappa 1. The interaction of the two kappa germ line promoters with nuclear binding factors is also examined. The potential role of these germ line transcripts in establishing the rearrangement potential of the locus is discussed. PMID- 2109188 TI - SAS1 and SAS2, GTP-binding protein genes in Dictyostelium discoideum with sequence similarities to essential genes in Saccharomyces cerevisiae. AB - We have identified two novel, very closely related genes, SAS1 and SAS2, from Dictyostelium discoideum. These encode small, approximately 20-kilodaton proteins with amino acid sequences thought to be involved in interaction with guanine nucleotides. The protein sizes, spacings of GTP-binding domains, and carboxyl terminal sequences suggest their relationship to the ubiquitous ras-type proteins. Their sequences, however, are sufficiently different to indicate that they are not true ras proteins. More extensive sequence identity (approximately 55%) is shared with the YPT1 and SEC4 proteins from Saccharomyces cerevisiae. These yeast proteins are essential for growth and are believed to be involved in intracellular signaling associated with membrane function. SAS1 and SAS2 exhibit distinct patterns of genomic organization and developmentally regulated gene expression. SAS1 contains introns and is associated with a developmentally regulated repetitive element. SAS2 is colinear with its mRNA and does not appear to be closely linked with this repetitive element. Both genes are expressed during growth and throughout development. SAS1 is maximally expressed during cytodifferentiation, when two sizes of SAS1 mRNA are detectable. SAS2 mRNA levels are maximal during culmination. On the basis of the expression patterns of the SAS genes and their relationship to the YPT1 and SEC4 genes, we discuss possible functions of the SAS proteins. PMID- 2109187 TI - Identification of a novel factor that interacts with an immunoglobulin heavy chain promoter and stimulates transcription in conjunction with the lymphoid cell specific factor OTF2. AB - The tissue-specific expression of the MOPC 141 immunoglobulin heavy-chain gene was studied by using in vitro transcription. B-cell-specific transcription of this gene was dependent on the octamer element 5'-ATGCAAAG-3', located in the upstream region of this promoter and in the promoters of all other immunoglobulin heavy- and light-chain genes. The interaction of purified octamer transcription factors 1 and 2 (OTF1 and OTF2) with the MOPC 141 promoter was studied by using electrophoretic mobility shift assays and DNase I footprinting. Purified OTF1 from HeLa cells and OTF1 and OTF2 from B cells bound to identical sequences within the heavy-chain promoter. The OTF interactions we observed extended over the heptamer element 5'-CTCAGGA-3', and it seems likely that the binding of the purified factors involves cooperation between octamer and heptamer sites in this promoter. In addition to these elements, we identified a second regulatory element, the N element with the sequence 5'-GGAACCTCCCCC-3'. The N element could independently mediate low levels of transcription in both B-cell and HeLa-cell extracts, and, in conjunction with the octamer element, it can promote high levels of transcription in B-cell extracts. The N element bound a transcription factor, NTF, that is ubiquitous in cell-type distribution, and NTF was distinct from any of the previously described proteins that bind to similar sequences. Based on these results, we propose that NTF and OTF2 interactions (both with their cognate DNA elements and possibly at the protein-protein level) may be critical to B-cell-specific expression and that these interactions provide additional pathways for regulating gene expression. PMID- 2109189 TI - Activation of alpha-protein kinase C leads to association with detergent insoluble components of GH4C1 cells. AB - TRH and phorbol dibutyrate (PDBu) stimulate PRL secretion and synthesis from GH4C1 rat pituitary cells through activation of protein kinase C (PKC). TRH responses are mediated by increases in cellular levels of two PKC activators, Ca2+ and diacylglycerol (DAG), whereas PDBu acts as a DAG analog. We conducted experiments to compare the effects of Ca2+ and PDBu/DAG on alpha-PKC redistribution and to determine to what components of the particulate fraction activated alpha-PKC associates. Subcellular fractionation experiments demonstrated that TRH and PDBu both caused chelator-stable association of alpha PKC with the particulate fraction. In contrast, Ca2+-mediated association with the particulate fraction was not chelator stable. Immunocytofluorescence experiments also demonstrated that TRH, PDBu, and increased cytosolic Ca2+ (due to ionomycin or K+ depolarization) caused redistribution. The effect of TRH was rapid and transient, similar to TRH stimulation of phospholipase C. The translocated alpha-PKC in the particulate fraction from TRH- or PDBu-treated cultures was not solubilized with Triton X-100. In comparable studies using an immunofluorescence assay, alpha-PKC immunofluorescence remained in detergent insoluble preparations from TRH- and PDBu-stimulated, but not resting cells. The association of activated alpha-PKC with chelator- and detergent-insoluble material suggested that activated alpha-PKC may be associated with membrane and cytoskeletal components. PMID- 2109190 TI - Dentatorubro-pallidoluysian atrophy of the myoclonus epilepsy type with posterior column degeneration. AB - Dentatorubro-pallidoluysian atrophy (DRPLA) has a variable clinical presentation but the pathology is routinely confined to cerebellifugal and pallidofugal systems. We present a case of DRPLA of the myoclonus epilepsy type in which prominent posterior column degeneration was added to the pathological picture. This case illustrates the concept that the neurodegenerative diseases can be a continuum of both clinical and pathological presentations. PMID- 2109191 TI - Training course on Drosophila somatic genotoxicity assays in Mexico. PMID- 2109192 TI - Drosophila wing-spot test: improved detectability of genotoxicity of polycyclic aromatic hydrocarbons. AB - The somatic mutation and recombination tests (SMART) using eyes or wings in the fruit fly Drosophila melanogaster are flexible and sensitive systems for the detection of genotoxicity of individual chemical compounds and complex mixtures. It is of special interest that adults and larvae possess cytochrome P-450 dependent activation systems able to metabolize most promutagens, e.g., nitrosamines, aflatoxins, pyrrolizidine alkaloids, safrole, etc. The polycyclic aromatic hydrocarbons (PAHs) represent a class of promutagens poorly detectable in Drosophila genotoxicity systems. Therefore, new tester strains for the wing spot test were constructed by introducing chromosomes 1 and 2 from a wild-type strain with increased cytochrome P-450-dependent metabolism linked to a gene on chromosome 2. Previous investigations with the new strains showed their increased detection capability for diethylnitrosamine. Comparative tests with the 3 PAHs benzo[a]pyrene, benz[a]anthracene and 7,12-dimethylbenz[a]anthracene demonstrate, in a reproducible way, that with the new strains all 3 can be detected as active genotoxic compounds. The dose-response curves for all compounds show a plateau with higher exposures. This is interpreted as indicative of a saturation of the cytochrome P-450-dependent activation systems. PMID- 2109193 TI - A statistical evaluation of the reproducibility of micronucleus, sister-chromatid exchange, thioguanine-resistance and ouabain-resistance assays in V79 cells exposed to ethyl methanesulfonate and 7,12-dimethylbenz[a]anthracene. AB - In contrast to the "validation" of short-term in vitro genotoxicity assays by concordance with the rodent cancer bioassay, the present report describes the multiple replication of 4 short-term tests with V79 cells (micronucleus assay, MN; sister-chromatid exchange, SCE; ouabain resistance. OUR; and thioguanine resistance, TGR) within the same assay system following exposure to each of two genotoxins, ethyl methanesulfonate (direct acting) and 7,12 dimethylbenz[a]anthracene (indirect acting). Reproducibility, proportion of genotoxins correctly identified, and proportion of non-genotoxins correctly identified by each test were each determined statistically. Decision rules were formulated to declare a positive response in each assay, and overall accuracy of each was determined. Statistical analysis of the data, obtained under standardized test conditions, showed that for these two chemicals SCE identified 100% of genotoxins and 86% of non-genotoxins, with overall accuracy of prediction of 93%; TGR identified 98% of genotoxins and 74% of non-genotoxins, with overall accuracy of 86%; MN identified 78% of genotoxins and 84% of non-genotoxins, with overall accuracy of 81%; while OUR indicated 100% of genotoxins, but only 50% of non-genotoxins, and only 76% overall accuracy. The results suggested that the best overall accuracy of classification with the V79 assay system could be achieved by measurement of SCE in combination with thioguanine resistance. PMID- 2109194 TI - Inhibition of induction of adaptive response by o-vanillin in Escherichia coli B. AB - Mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were strongly enhanced in the presence of o-vanillin in E. coli B. The enhancement was also observed in uvrA, umuC, recA, polA, or alkB mutants. This effect was lower in an alkA mutant, but was restored in an alkA umuC double mutant. By contrast, the enhancing effect was almost blocked in an ada and ada umuC double mutant. It was necessary to add simultaneously MNNG and o-vanillin to the growth medium. Further investigations were conducted on the induction of ada and umuC genes using ada' lacZ' and umuC'-lacZ' plasmids. o-Vanillin suppressed the induction of the ada gene by MNNG treatment, but not that of the umuC gene. In fact expression of the umuC gene was induced by lower concentrations of MNNG in the presence of o vanillin. The results suggest that o-vanillin inhibits induction of the adaptive response, and consequently, the MNNG-induced mutation frequency is increased due to unrepaired O6-methylguanine. PMID- 2109195 TI - Prevention of acute graft rejection by the prostaglandin E1 analogue misoprostol in renal-transplant recipients treated with cyclosporine and prednisone. AB - Prostaglandins of the E series have been shown to have immunosuppressive properties. To study the effects of the prostaglandin E1 analogue misoprostol on renal function and graft rejection after transplantation, we conducted a randomized, double-blind, placebo-controlled trial in 77 renal-allograft recipients. The subjects received misoprostol (200 micrograms four times daily by mouth; n = 38) or placebo (n = 39) for the first 12 weeks after transplantation, in addition to standard immunosuppression with cyclosporine and prednisone. They were then observed for an additional four weeks after the drug or placebo was discontinued. Treatment with misoprostol was associated with a significant improvement in renal function as judged by the mean (+/- SEM) serum creatinine concentration (128 +/- 7 vs. 158 +/- 11 mumol per liter after 12 weeks; P = 0.03) and creatinine clearance (84 +/- 6 vs. 69 +/- 5 ml per minute per 1.73 m2 of body surface area; P = 0.05). There was a significant reduction in the incidence of acute rejection in the group treated with misoprostol as compared with the placebo group (10 of 38 vs. 20 of 39; P = 0.02), and there was less need for rehospitalization after transplantation (4 +/- 1 days with misoprostol vs. 10 +/- 2 days for placebo; P = 0.03). Although blood levels of cyclosporine did not differ significantly between the groups, they tended to be higher in the misoprostol group, as did the incidence of acute nephrotoxicity due to cyclosporine (13 of 38 vs. 8 of 39). Infectious complications tended to be fewer in the misoprostol-treated group (14 of 38 vs. 21 of 39). We conclude that misoprostol improves renal function and safely reduces the incidence of acute rejection in renal-transplant recipients treated concurrently with cyclosporine and prednisone. PMID- 2109196 TI - Family decision making on trial. Who decides for incompetent patients? PMID- 2109197 TI - Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. AB - Progressive bone loss in osteoporosis results from bone resorption in excess of bone formation. We conducted a double-blind study in 66 women with postmenopausal osteoporosis of therapy with etidronate, a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned in equal numbers to receive oral etidronate (400 mg per day) or placebo for 2 weeks, followed by a 13-week period in which no drugs were given. This sequence was repeated 10 times, for a total of 150 weeks. Daily oral supplementation with calcium and vitamin D was given throughout the study to both groups. Vertebral bone mineral content was measured by dual-photon absorptiometry; spinal radiographs were assessed to identify new vertebral fractures. Vertebral bone mineral content increased significantly (P less than 0.01) after 150 weeks of etidronate therapy (5.3 percent; 95 percent confidence interval, 2.0 to 8.6; n = 20) but decreased with placebo (-2.7 percent; 95 percent confidence interval, -7.3 to 1.9; n = 20). The difference between groups was 8.0 percentage points (P less than 0.01; 95 percent confidence interval, 2.4 to 13.6). The rates of fracture were significantly different for the period from week 60 to week 150 between the etidronate and placebo groups (6 vs. 54 fractures per 100 patient-years; P = 0.023). No adverse clinical, biochemical, or bone histomorphometric effects of treatment were observed. We conclude that at the end of nearly three years, etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content and, after approximately one year of treatment, a significant decrease in the rate of new vertebral fractures. PMID- 2109198 TI - ddI--a good start, but still phase I. PMID- 2109200 TI - AIDS: facts, please. Interview by Tim Rice. PMID- 2109199 TI - Detection of IgG and IgE antibodies to Aspergillus fumigatus in human sera by immunogold assay. AB - An immunogold assay (IGA) was developed to detect IgG and IgE antibodies to Aspergillus fumigatus. Sixteen sera from patients with allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, and normal controls were studied. All sera were also evaluated for antibodies against A. fumigatus by biotin-avidin linked enzyme immunosorbent assay (BALISA) and by agar gel double diffusion method. A. fumigatus specific IgG and IgE antibodies could be detected by IGA in all the patients' sera but not in the sera of normal controls. Both IgG and IgE antibodies to A. fumigatus could be demonstrated in all the sera by BALISA and normal controls showed only low levels of these antibodies. There was a positive correlation between the degree of reactivity detected by IGA, the BALISA titer and the precipitins by agar gel diffusion. It can be concluded that IGA is a reliable, sensitive and simple method capable of detecting both IgG and IgE antibodies against A. fumigatus in patient serum. PMID- 2109201 TI - A conflict in embryo. PMID- 2109202 TI - AIDS/HIV: no Mr Average. Interview by Charlotte Alderman. PMID- 2109203 TI - Nursing overseas: nursing revolution. PMID- 2109204 TI - Recent venous ulcer treatments. PMID- 2109205 TI - The problems facing men as health visitors. PMID- 2109206 TI - Mental handicap and HIV: the issues. PMID- 2109207 TI - A strategy for nursing. Nursing targets for action in 1991. PMID- 2109208 TI - A strategy for nursing. Recruitment: the challenge. PMID- 2109209 TI - Primary health care. Schooling for change. PMID- 2109210 TI - Primary health care. Reproductive health. PMID- 2109211 TI - Primary health care. Prescribing realities. PMID- 2109212 TI - Primary health care. Promoting good food and health. PMID- 2109213 TI - Primary health care. The shape of things to come. PMID- 2109214 TI - Primary health care. Screening the elderly. PMID- 2109215 TI - Ambulance dispute: a bitter legacy. PMID- 2109216 TI - Leukaemia: fuelling the argument. PMID- 2109217 TI - The role of surgeon and procedure gloves in infection control. PMID- 2109218 TI - A strategy for nursing. Targets for 1991: practice. PMID- 2109219 TI - Health visiting: preparation and education for practice. PMID- 2109220 TI - Computerisation of care planning. PMID- 2109221 TI - South Africa: moving slowly towards equality. PMID- 2109222 TI - Politics: becoming anaerobic. PMID- 2109224 TI - Open all hours. PMID- 2109223 TI - Management: consenting adults. PMID- 2109225 TI - Intensive care and transplant surgery nursing. PMID- 2109226 TI - Community care--will the government pay? PMID- 2109227 TI - Open learning: open minds. PMID- 2109228 TI - ECG file. PMID- 2109229 TI - NHS reforms: allies prepare battle plan. PMID- 2109230 TI - Daphne Parish: a quiet hell. Interview by Jackie O'Byrne. PMID- 2109231 TI - Romania appeal: your help needed. PMID- 2109232 TI - Life in a Calcutta street clinic. Part 2. PMID- 2109233 TI - Psoriasis--a disease with no benefits. PMID- 2109234 TI - Psoriasis: whose skin is it anyway? PMID- 2109235 TI - A strategy for nursing. Staff deployment and skill mix. PMID- 2109236 TI - Intravenous infusion controllers. PMID- 2109238 TI - Spiritual health care and the nurse. PMID- 2109237 TI - Community health promotion. PMID- 2109239 TI - A model for mental handicap nursing. PMID- 2109240 TI - The demise of the external assessor. PMID- 2109241 TI - A practical guide to saving rainforests. PMID- 2109242 TI - Time for a rethink. PMID- 2109243 TI - A flexible program. PMID- 2109244 TI - Education: selling nursing short. PMID- 2109245 TI - Staying put. Interview by Jean Gray. PMID- 2109246 TI - Committee stage of the NHS bill. PMID- 2109247 TI - ECG file. PMID- 2109248 TI - GP contracts: scare in the community. PMID- 2109250 TI - NHS nursing homes: selling out. PMID- 2109249 TI - Florence Nightingale and the Royal Herbert. PMID- 2109251 TI - Caring for a child with a tracheostomy. PMID- 2109252 TI - Syringes: looking at infusion devices. PMID- 2109253 TI - Critical awareness in nurse education. PMID- 2109254 TI - Images of the Cuban health care system. PMID- 2109256 TI - Supply and demand. PMID- 2109255 TI - Stemming the flow by considering basic needs. PMID- 2109257 TI - Religious information--centres and sources. PMID- 2109258 TI - Informal carers--the forgotten army. PMID- 2109259 TI - Nursing's 'gold reserves'. PMID- 2109260 TI - AIDS focus. PMID- 2109261 TI - AIDS focus. Safer sex makes sense. PMID- 2109262 TI - AIDS focus. HIV roundup. PMID- 2109263 TI - Renal thrombotic microvascular disease associated with lupus anticoagulant. PMID- 2109264 TI - Fibrinolytic responses to 1-desamino-8-D-arginine-vasopressin in patients with congenital nephrogenic diabetes insipidus. AB - Fibrinolytic responses to infusion of 1-desamino-8-D-arginine-vasopressin (DDAVP) were assessed in 6 males with congenital nephrogenic diabetes insipidus (NDI), 6 carriers of the NDI gene and 6 normal control subjects. Tissue-type plasminogen activator (t-PA) activity and antigen increased significantly in normal subjects, while plasminogen activator inhibitor (PAI) activity decreased. None of these changes were observed in patients with NDI. In 2 female carriers, normal fibrinolytic responses were seen, while in the other carriers responses were delayed. These findings are consistent with the concept of a general V2-receptor defect in congenital NDI. DDAVP tests are of limited use in NDI carrier detection. PMID- 2109265 TI - Lithium carbonate orally increases renal sodium excretion. PMID- 2109266 TI - Arachidonic and docosahexanoic acid content of bovine brain myelin: implications for the pathogenesis of multiple sclerosis. AB - Lipids were extracted from bovine brain myelin using a mixture of hexane and isopropanol (3:2). Myelin lipids were resolved, using Sep Pak chromatography, into four fractions: Fraction 1 contained neutral lipids, fraction 2, free fatty acids, fraction 3, ethanolamine phospholipids and fraction 4, choline phospholipids. Doscosahexanoic (DHA) and arachidonic (AA) acids in these fractions were measured by RPHPLC. Fraction 2 was analyzed directly, the other three fractions were subjected to alkaline hydrolysis before analysis for DHA and AA. DHA and AA were not found in fraction 1. Both DHA and AA were found in fractions 2 and 3. Only AA was consistently found in fraction 4. These results were confirmed by GC. PMID- 2109267 TI - Plasma levels of vasoactive intestinal polypeptide and oxytocin in response to suckling, electrical stimulation of the mammary nerve and oxytocin infusion in rats. AB - The aim of the present study was to measure plasma levels of vasoactive intestinal polypeptide (VIP) and oxytocin following suckling, electrical stimulation of the mammary nerve and oxytocin infusion in lactating rats. Trunk blood was collected by decapitation after 5 and 20 min of suckling in conscious lactating rats. Repeated blood samples were drawn from the carotid artery in anesthetized rats, in connection with suckling, oxytocin infusion (0.22 nmol/l/kg/h) and electrical stimulation of the mammary nerve (5 V, 5 Hz, 2 ms). VIP and oxytocin levels were measured by radioimmunoassay. In conscious rats, VIP levels rose significantly from 18 +/- 5 to 102 +/- 30 pM after 5 min of suckling and to 123 +/- 25 pM after 20 min of suckling when milk ejection occurred. Oxytocin levels rose significantly from 90 +/- 24 to 269 +/- 45 pM during milk ejection. Suckling, oxytocin infusion and mammary nerve stimulation in anesthetized rats raised VIP levels significantly from 13 +/- 2, 18 +/- 5 and 10 +/- 2 to 43 +/- 8, 45 +/- 16 and 53 +/- 22 pM, respectively, whereas oxytocin levels rose from 111 +/- 34 to 294 +/- 66 pM after 20 min of suckling and to a peak value of 500 +/- 70 pM after oxytocin infusion. This study shows that VIP is elevated in plasma in lactating rats when the pups are suckling. The results showing that VIP levels rise following mammary nerve stimulation and oxytocin infusions indicate that both neurogenic and hormonal mechanisms can contribute to the regulation of VIP levels in plasma. PMID- 2109268 TI - Ultrastructural characterization of prolactin-like immunoreactivity in rat medial basal hypothalamus. AB - Prolactin-like immunoreactivity has been reported in the medial basal hypothalamus at the light microscopic level, in hypophysectomized rats. Here, with preembedding immunocytochemistry at the electron microscopic level, we have observed prolactin-immunoreactive neurons and synapses in the hypothalamus. Reaction product was discovered in medial basal hypothalamic neurons, which had typical large nucleoli and received axosomatic synapses. In the cytoplasm, reaction product was distinctly granular. Immunoreactive neurons were usually surrounded by nonreactive cells. Reaction product was also seen in dendrites, some of which had spines. Some axons in the hypothalamus contained reaction product, usually surrounded by nonreactive axons, and immunopositive synapses were detected both in the hypothalamus and in the midbrain. In a small number of cases immunoreactive axons could be seen synapsing on immunoreactive dendrites. PMID- 2109269 TI - Evidence for central and peripheral serotonergic control of corticosterone secretion in the conscious rat. AB - Serotonin (5-HT) and 5-HT agonists act on multiple 5-HT receptor subtypes to increase corticosterone secretion. The present experiments describe the effects of a highly selective 5-HT2 receptor agonist DOI [(+-)-1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane HCl] on plasma corticosterone in conscious, unrestrained, male rats with indwelling arterial and venous catheters. DOI (500 micrograms/kg, i.v.) increased plasma corticosterone levels 6- to 7-fold from 15 to 60 min. Pretreatment with the central 5-HT2 antagonist LY 53857 (100 micrograms/kg, i.v.) blocked the effect of DOI on corticosterone secretion at all times. The peripheral 5-HT2 antagonist xylamidine (100 micrograms/kg, i.v.) attenuated the corticosterone response elicited 15 min after DOI but did not alter the 60-min response. In contrast, dexamethasone pretreatment (350 micrograms/kg, s.c.) attenuated the corticosterone response to DOI at 15 min, but abolished the response at 60 min. The increase in corticosterone levels elicited 5 min after the nonselective 5-HT agonist quipazine (3 mg/kg, i.v.) was also reduced by xylamidine. These data suggest that 5-HT2 receptor agonists increase corticosterone secretion initially, in part, through a direct adrenal mechanism not entirely dependent on adrenocorticotropin, and at later times via a central, dexamethasone-suppressible mechanism. This raises the possibility that endogenous 5-HT in the adrenal medulla may act as a local paracrine to participate in the regulation of corticosterone secretion from the adrenal cortex. PMID- 2109270 TI - Evidence for the involvement of corticotropin-releasing factor in the inhibition of gonadotropin release induced by hyperprolactinemia. AB - The hypothesis was tested that corticotropin-releasing factor (CRF) is involved in the inhibition of gonadotropin secretion during chronic hyperprolactinemia. Two models of hyperprolactinemia were used, namely inoculation with the prolactin (PRL)-secreting tumor 7315b and implantation of isogenic pituitary glands. Gonadectomized, adrenalectomized male rats received a testosterone capsule and a corticosterone pellet and were inoculated subcutaneously with tumor 7315b. Similar rats without tumor served as controls. The rats were studied 3-4 weeks later while anesthetized with urethane. Plasma testosterone and corticosterone were similar in the two groups of rats. Compared to controls, the tumor-bearing rats had significantly higher plasma levels of PRL (100-fold increase) and adrenocorticotropin (ACTH; 3-fold increase), whereas plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) had significantly decreased to 15 and 40%, respectively. CRF release into hypophysial stalk plasma was higher in rats with tumor 7315b than in controls (298 +/- 23 vs. 197 +/- 28 pg/h), and hypothalamic CRF content had increased from 3.0 +/- 0.3 to 4.3 +/- 0.3 ng. Male rats received 3 pituitary glands under the kidney capsule. Sham-operated rats served as controls. They were studied 5-7 weeks later while anesthetized with urethane. Compared to controls, pituitary-grafted rats had larger adrenals (49 +/ 4 vs. 34 +/- 2 mg), higher plasma PRL (156 +/- 18 vs. 52 +/- 8 ng/ml), ACTH (0.46 +/- 0.05 vs. 0.22 +/- 0.02 ng/ml) and corticosterone (455 +/- 39 vs. 268 +/ 14 ng/ml), and lower plasma levels of LH (21 +/- 2 vs. 41 +/- 6 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109271 TI - Reduction in testicular function in rats. I. Reduction by a specific gonadotropin releasing hormone antagonist in fetal rats. AB - A gonadotropin-releasing hormone (GnRH) antagonist, when injected 24 h before sacrifice to rat fetuses, did not modify plasma testosterone concentrations in males on day 18 of gestation but it did on days 19, 20 and 21. This GnRH antagonist reduced plasma luteinizing hormone (LH) levels and increased pituitary LH content in both male and female 19-day-old fetuses from mothers adrenalectomized on day 14 of gestation. An inverse relationship between plasma testosterone and LH levels was noted in males and females, on days 19 and 21. These data suggest that the hypothalamic control of gonadotropic function is operating by day 19 of fetal life and that a negative feedback of testosterone on LH and probably GnRH release is also operating in rat fetuses on days 19 and 21 of gestation. PMID- 2109272 TI - Reduction in testicular function in rats. II. Reduction by dexamethasone in fetal and neonatal rats. AB - Chronic administration of dexamethasone in drinking water to maternal rats from days 15 to 21 of gestation (1) reduced plasma testosterone concentrations in male fetuses between days 19 and 21 but not earlier on day 18 and abolished the prenatal peak of plasma testosterone which normally occurs on day 19 of gestation, and (2) suppressed the postnatal surge of plasma testosterone in male newborns 1.5 and 2 h after delivery at term by cesarean section. The administration of dexamethasone to male fetuses at birth induced 1 h later a slight but not significant increase in hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary luteinizing hormone (LH) contents, reduced drastically plasma LH levels and completely prevented the postnatal surge of plasma testosterone which occurred normally in littermate controls. A rise in pituitary LH content, and a sharp reduction in plasma LH and testosterone concentrations were noted in 19-day-old male fetuses whose mothers were acutely treated with dexamethasone on day 18 of gestation. Similar evolutions for LH were observed in littermate females. These results suggest that the inhibitory effects of exogenous glucocorticoids on testosterone secretion could be mediated in both fetuses and newborns at least partially through suppression of the hypothalamic and pituitary secretion of GnRH and LH, respectively, and provide insight how stress or hormone imbalance may affect the development of this neuroendocrine system. PMID- 2109273 TI - Differential effects of haloperidol on the rat pituitary: decreased biosynthesis, processing and release of anterior lobe pro-opiomelanocortin. AB - The effects of chronic haloperidol treatment on pro-opiomelanocortin (POMC) synthesis, processing, and release in the anterior (AL) and intermediate (IL) lobes of the rat pituitary were studied. In the IL, 14 days of haloperidol administration promoted an increase in the level of POMC mRNA, and a corresponding elevation of levels of beta-endorphin (beta E), alpha-melanocyte stimulating hormone (MSH), and gamma 3 MSH. In the AL, a reduction of POMC mRNA as well as immunoreactive beta E, adrenocorticotropin (ACTH), and gamma 3 MSH was observed. Column chromatography revealed that this treatment promoted an apparent alteration of POMC processing in AL: the conversion of larger, precursor-sized peptides to smaller, more-processed forms was relatively inhibited. Circulating levels of both N-acetyl-beta E and corticosterone were elevated following haloperidol challenge in drug-naive animals. Resting plasma levels of both, however, were not changed following chronic haloperidol treatment. Pituitary culture studies demonstrated that chronic haloperidol treatment increased the releasability of IL-derived products, while simultaneously decreasing the releasability of those products from the AL. These results suggest that pituitary POMC biosynthesis, processing and release are under at least partial dopaminergic control in both the IL and the AL of the pituitary, but by different mechanisms; chronic haloperidol treatment upregulates the POMC system in IL, but downregulates it in AL, despite similarities of the responses of both lobes to acute haloperidol challenge. PMID- 2109274 TI - Clonidine suppresses copulatory behavior and erectile reflexes in male rats: lack of effect of naloxone pretreatment. AB - Adrenergic transmitters and opioid peptides are implicated in the regulation of male sexual behavior. In the present studies we examine a possible interaction between these two neurochemical systems in the regulation of components of male sexual behavior. In mating tests, clonidine (0.25 mg/kg, 6 min pretest) induced a profound deficit in intromissive and ejaculatory behavior whereas naloxone (5 mg/kg, 20 min pretest) evinced a facilitation of ejaculatory behavior, evidenced by decreases in the ejaculation latency in the initial copulatory series and by decreases in ejaculation latency and intercopulatory interval in the second copulatory series. Importantly, prior treatment with naloxone did not prevent or attenuate the copulatory suppression induced by clonidine. In ex copula penile reflex tests, clonidine (0.25 mg/kg, 6 min pretest) decreased the incidence of seminal emission and the number of penile responses (erections, cups and flips). Naloxone (5 mg/kg, 20 min pretest) was without effect on any of the parameters of penile reflex activity and, further, failed to prevent or attenuate the erectile suppression induced by clonidine. A final study evaluated the dose-response relationship of clonidine-induced erectile dysfunction. A similar degree of erectile dysfunction was observed after 0.005, 0.025 or 0.25 mg/kg clonidine, whereas 0.0005 mg/kg was without effect. Previous studies demonstrated a dose dependent inhibition of mounting, intromissive and ejaculatory behavior, with 0.25 mg/kg selectively eliminating ejaculatory behavior in mating tests. These data demonstrate a dose-dependent inhibition of penile reflexes, with inhibition occurring at doses lower than those required to induce copulatory dysfunction. Further, we suggest that opioid receptors sensitive to naloxone blockade are not involved in the clonidine-induced suppression of copulatory or erectile function. PMID- 2109275 TI - Effects of treatment with a lithium-imipramine combination on components of adenylate cyclase in the cerebral cortex of the rat. AB - This study was aimed at investigating the effects of treatment with a lithium imipramine combination on the activity of adenylate cyclase in membranes from the cerebral cortex of the rat. Treatment with (1) lithium for 2 weeks, yielding a level of lithium in serum of 0.54 +/- 0.12 mmol/l, (2) imipramine for 4 weeks (10 mg/kg i.p. twice per day) and (3) a combination of the two drugs reduced isoprenaline-induced stimulation of adenylate cyclase by GTP, with a greater decrement with the combined treatment. None of the treatments exerted any effect on the activity of the enzyme stimulated by GTP alone. Lithium ex vivo inhibited the calcium (Ca2+)- and Gpp(NH)p-stimulated activity of adenylate cyclase, but imipramine ex vivo did not affect the activity of adenylate cyclase, stimulated by these activators. The lithium-imipramine treatment reduced Ca2(+)- and Gpp(NH)p-stimulated activity of adenylate cyclase, but this was not different from that observed in the lithium-treated group. In conclusion, the beta adrenoceptor-stimulated adenylate cyclase was affected markedly by administration of lithium and imipramine together. In contrast to lithium ex vivo, imipramine ex vivo did not impair the activity of either the guanine nucleotide regulatory protein or the catalytic subunit, since no change in activity was observed in the presence of beta,gamma-imidoguanosine-5' triphosphate (Gpp(NH)p) or Ca2+. Furthermore, lithium ex vivo exerted its post-receptor effects on the adenylate cyclase, independent of imipramine. The decrement in activity of beta-adrenergic adenylate cyclase, induced by administration of the two drugs together may partly be involved in the therapeutic action of the augmentation of antidepressants by lithium in refractory depression. PMID- 2109276 TI - D-serine antagonized phencyclidine- and MK-801-induced stereotyped behavior and ataxia. AB - D-Serine, a selective agonist at the strychnine-insensitive glycine binding site, antagonized PCP-induction of stereotyped behavior and ataxia in a dose-dependent manner. At intraventricular doses of 0.1, 0.5 and 1 mumol/rat, D-serine significantly attenuated PCP-induction of stereotyped behavior in rats. Only doses of 0.5 and 1.0 mumol/rat of D-serine antagonized PCP-induction of ataxia. D Serine (0.5 mumol/rat) also antagonized MK-801 induced stereotyped behavior and ataxia. These results suggest that agonists at the strychnine-insensitive glycine site may be clinically useful as a novel class of atypical antipsychotic agents. PMID- 2109277 TI - Reciprocal regulation of preprothyrotropin-releasing hormone (TRH) mRNA in the rat anterior hypothalamus by thyroid hormone: dissociation from TRH concentrations during hypothyroidism. AB - TRH mRNA has not been quantified concomitantly with TRH itself to examine graded effects of thyroid hormones (TH) upon TRH gene transcriptional regulation and post-transcriptional expression. To examine such TH effects, rats were rendered thyrotoxic with L-T3 (50 micrograms per 100g body weight) or hypothyroid by total thyroidectomy. After decapitation, frozen coronal brain sections were prepared in a matrix for hypothalamic micropunches. PreProTRH mRNA was quantified in punch pools by slot-blot hybridization and densitometry, using a 32P 1.2Kb rat riboprobe (gift of Drs. S. Lee and R. Goodman). T3 toxicosis resulted in parallel reductions in PreProTRH mRNA (-45%) and TRH concentrations determined by RIA ( 43%), 1.1 versus 1.9 ng/mg protein, p less than 0.01. Conversely, elevations in PreProTRH mRNA were stimulated by hypothyroidism on Day 14 (+32%). However, TRH concentrations were reduced paradoxically from 2.2 +/- 0.05 ng/mg protein to 0.68 +/- 0.03, p less than 0.01. No changes, in contrast, were identified in whole hypothalamic extracts in either PreProTRH mRNA or TRH after T3 treatment. It is concluded that TH do exert inhibitory effects upon PreProTRH mRNA transcription, and in the specific hypothalamic nucleus concerned with thyroid regulation (PVN). The failure of TRH concentrations to rise concordantly with activated TRH gene transcription in hypothyroidism suggests that TH may exert inhibitory effects upon PreProTRH mRNA translation, in addition to inhibition of TRH gene transcription and TRH secretion. PMID- 2109278 TI - [Enteral nutrition in the pre- and postoperative therapy of gastric neoplasms. Comments on 21 cases]. AB - Results of personal experience of the application of enteral nutrition in a group of patients (21) submitted to surgery for gastric cancer are reported. Enteral nutrition proved easy to perform, provided a significant improvement in some of the parameters considered in the study, was without significant complications and presented acceptable management costs. PMID- 2109279 TI - [A case of meningococcal sepsis]. AB - We describe a 7-years boy by with a meningococcal sepsis due to Neisseria Meningitidis, with very serious evolution of cutaneous necrosis, initial D.I.C. and heart failure. The clinical picture do not improve with antibiotic therapy (CAF-penicillin), but the association ceftriaxone + tobramycin results in rapid improvement. The cutaneous necrosis, especially evident on gluteus, arms and legs, were treated locally with AgNO3 and penicillin-solution. After 4 weeks of treatment, also this cutaneous involvement improved and now the boy is healthy, without residual signs neither systemic nor cutaneous. PMID- 2109280 TI - The renal response to an acute protein load in man: clinical perspective. PMID- 2109281 TI - Association of glomerular and interstitial mononuclear leukocytes with different forms of glomerulonephritis. AB - Immunophenotyping of mononuclear leukocytes was performed in renal tissue obtained from 69 patients with different forms of glomerulonephritis (GN) and from ten donors' kidneys for transplantation used as controls. A panel of monoclonal antibodies was used in the immunoperoxidase technique on frozen sections to define B- and T-lymphocyte subpopulations, NK cells and monocytes/macrophages, as well as the expression of HLA class II antigens-DQ, -DR and -DP. Quantification of labelled leukocytes revealed a significant increase of CD4+ and CD8+ T-cells in glomeruli of rapidly progressive glomerulonephritis, membranoproliferative glomerulonephritis and even of focal gomerulosclerosis. The number of glomerular monocytes/macrophages was significantly increased only in rapidly progressive glomerulonephritis, whereas in membranoproliferative glomerulonephritis it was decreased. No differences to normal tissue were detected in glomeruli for all other types of inflammatory cells. Interstitial cells were mostly T-lymphocytes in all forms of glomerulonephritis. In all groups the CD4+/CD8+ ratio was somewhat greater than 1 and even about 2 in rapidly progressive glomerulonephritis. Only in particular case was this ratio inversed. High expression of HLA class II antigens was observed on interstitial mononuclear leukocytes, as a sign of their activation. The excess of HLA-DQ-positive cells over the sum of CD14+ and CD20+ cells provides evidence not only for presence of activated T-lymphocytes but perhaps also for accumulation of renal dendritic cells in the interstitium in glomerulonephritis associated with interstitial infiltration. PMID- 2109282 TI - Renal granulomatous sarcoidosis: report of six cases. AB - Six cases of chronic renal failure related to granulomatous renal sarcoidosis are reported and compared with data in the literature. The particular features of sarcoidosis granulomatous interstitial nephritis should be emphasised because presentation may be misleading. Renal failure usually presents with a rapidly progressive course, either isolated or associated with mild proteinuria and sterile leukocyturia, while extrarenal localisations may be absent. Diagnosis should be suspected on the basis of elevated or paradoxically normal serum calcium concentrations, due to increased plasma concentrations of calcitriol, while immunoreactive circulating parathormone concentrations are depressed. Calcitriol as well as angiotensin-converting enzyme could represent unregulated secretion products from granulomatous tissue and their plasma concentrations may roughly reflect activity of the disease. Early corticosteroid treatment dramatically improves renal function but long-term renal prognosis may be oblitered due to progressive chronic renal failure related to fibrosis scarring. PMID- 2109283 TI - Diffuse intermyocardiocytic fibrosis in uraemic patients. AB - At post-mortem we examined heart tissue of (i) 31 patients with uraemia not on dialysis, (ii) 42 patients on haemodialysis for less than 6 months, (iii) 60 patients on haemodialysis for more than 6 months, (iv) 16 patients after renal transplantation, and (v) 11 patients on CAPD. Patients with stenosing coronary lesions were excluded. Diffuse non-coronary intermyocardiocytic fibrosis, assessed by a score system in trichrome-stained sections, was found in 91% of chronically uraemic patients, but not in non-hypertensive, non-diabetic controls. The lesion was present even in non-dialysed uraemic patients; in dialysed patients its severity was related to the duration of dialysis; it was demonstrable even years after renal transplantation. On electron-microscopy, collagen fibres were seen, while beta 2-M amyloid was consistently absent. Logistic regression analysis showed that uraemia was a determinant of intermyocardiocytic fibrosis independent of hypertension, diabetes mellitus, anaemia, heart weight, and presence or absence of dialysis procedure. PMID- 2109284 TI - Value of serum aluminium monitoring in dialysis patients: a multicentre study. AB - The clinical relevance of regular serum aluminium monitoring in dialysis patients was investigated in a multicentre study by 6-monthly determination of the serum aluminium during 4 consecutive years. In a group totalling 1193 patients, a striking decrease of mean serum aluminium was observed the last 2 years of the study. This phenomenon was accompanied by a substantial reduction of the prescribed dose of aluminium hydroxide (Al(OH)3) and its partial replacement by calcium carbonate (CaCO3) and/or magnesium hydroxide (Mg(OH)2). Under this policy serum phosphate control remained satisfactory. In all the centres, water treatment was found to be adequate, yielding dialysate aluminium around 2 micrograms/l. Dialysis patients with clinically overt liver disease showed a significantly greater median serum aluminium concentration than that observed in a control dialysis population. Compared to the latter group, the median serum aluminium concentration of dialysis patients with diabetes mellitus did not differ significantly. Results further indicated that patients with biopsy-proven osteomalacia presented a significantly greater median serum aluminium compared to that of patients without osteomalacia. We demonstrated that a serum aluminium of 60 micrograms/l provides a relatively sensitive (82%) and specific (86%) index for the detection of aluminium-related bone disease (ARBD). Provided the aluminium determinations are performed by a qualified laboratory, serum monitoring in dialysis patients (a) allows the safer use of aluminium-containing phosphate binders, and (b) is of value in the diagnosis of overload/toxicity. PMID- 2109285 TI - Five years' experience with Hickman catheters as temporary access for haemodialysis. AB - Two different types of Hickman catheters were used as central venous access for haemodialysis. The device was implanted in 58 patients with chronic renal failure, already undergoing haemodialysis, because of thrombosis or infection of the previous vascular access, in order to permit immediate treatment and in nine patients with acute renal failure, as a 'first choice' method suitable either for dialysis or for parenteral infusions and nutrition. The catheter was inserted, under local anaesthesia, through the external jugular vein up to the right atrium; the haemodialysis treatment was carried out by single-needle technique 3 4 times weekly and all the catheters were filled daily with heparinised saline and Miconazole solution. The mean duration was 76 +/- 93 days with an overall of 2253 treatments. The flow rate ranged between 150 and 290 ml/min, with acceptable recirculation rate and biochemistry similar to that of standard dialysis. The complication rate was 20%, including thromboses and infections; no operative mortality nor major complications were observed. Based on these data, we believe that the Hickman catheter represents the ideal method of temporary access for haemodialysis. PMID- 2109286 TI - Hypophosphataemia after renal transplantation: relationship to immunosuppressive drug therapy and effects on muscle detected by 31P nuclear magnetic resonance spectroscopy. AB - Plasma phosphate values were examined in 72 renal transplant patients in a randomised trial of immunosuppression with azathioprine and prednisolone versus cyclosporin alone. From 21 to 77 days after transplantation, in patients with plasma creatinine concentrations of 75-150 mumol/l, mean plasma phosphate was 0.98 (SEM 0.04) mmol/l in cyclosporin-treated patients, compared with 0.65 (SEM 0.12) mmol/l in cyclosporin-treated patients receiving pulse methylprednisolone for rejection (P less than 0.003), and 0.68 (SEM 0.02) mmol/l in patients treated with azathioprine and prednisolone (P less than 0.001). There was no difference between the mean plasma creatinine of these groups of patients. A preliminary study by nuclear magnetic resonance spectroscopy of four patients with asymptomatic chronic hypophosphataemia showed reduced concentrations of intracellular phosphate in resting muscle, and further abnormalities developed on exercise. Thus, exogenous steroid administration is a major contributing factor of hypophosphataemia in the early post-transplant period. In addition chronic hypophosphataemia may be associated with reduced intracellular inorganic phosphate concentrations detectable by nuclear magnetic resonance spectroscopy, although these changes are not apparently associated with any clinical symptoms. PMID- 2109287 TI - Absence of acute nephrotoxicity with low doses of cyclosporin: experimental study in the rat. AB - No study has, to our knowledge, evaluated the acute effects of low immunosuppressive doses of cyclosporin (CsA) on renal function. To establish whether a relationship exists between the dosage of CsA and the onset of nephrotoxicity, 28 rats were studied by renal clearances before (control) and after i.v. administration of different doses of CsA: 3 mg/kg b.w. (group 1); 7 mg/kg b.w. (group 2); 11 mg/kg b.w. (group 3); 15 mg/kg b.w. (group 4). No change in renal function was observed between control and the post-CsA period in groups 1 and 2. GFR (inulin clearance) was decreased vs the control period in group 3 and group 4 (-22% and -37%, respectively, P less than 0.001); the difference between these two groups was statistically significant (P less than 0.01). Effective renal plasma flow (PAH clearance) was similarly decreased in groups 3 and 4 vs their control periods (-21% and -28%, respectively, P less than 0.001) due to the increase of total renal vascular resistance (+41% and +42%, respectively, P less than 0.001). Filtration fraction was significantly decreased by CsA in group 4 (P less than 0.01 vs the control period). PAH renal extraction, urinary volume, and sodium and potassium excretion were similar in all groups before and after CsA. PRA and ADH were significantly increased only in group 4 (P less than 0.01) vs the baseline values. A high and significant relationship was detected between CsA dosage and the decrease of GFR (r = 0.81, P less than 0.001) and RPF (r = 0.612, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109288 TI - Successful medical management of presumed spontaneous decapsulation of a transplant kidney. PMID- 2109289 TI - Erythrocyte indices during treatment with human recombinant erythropoietin in dialysis patients. PMID- 2109290 TI - The washout kinetics of intraperitoneal IgG in CAPD patients. PMID- 2109291 TI - Melatonin modulates diacylglycerol and arachidonic acid metabolism in the anterior pituitary of immature rats. AB - In pituitary glands of immature rats prelabeled in vitro with [3H]arachidonic acid, melatonin diminished the luteinizing hormone-releasing hormone (LHRH) induced increase in [3H]diacylglycerol accumulation as well as [3H]arachidonic acid release from the tissue. Melatonin reduced also LHRH-stimulated incorporation of [3H]glycerol into pituitary [3H]diacylglycerol. The effect was day-time dependent: in the evening experiment melatonin was effective at 0.1 nM concentration while in the morning it had no effect even at 10 nM concentration. The effect of melatonin was also abolished by pretreatment with pertussis toxin. Diacylglycerol and/or arachidonic acid might serve as 2nd messengers transducing the effect of melatonin at the cellular level. PMID- 2109292 TI - Aluminum induces the in vitro aggregation of bovine brain cytoskeletal proteins. AB - The addition of aluminum to purified cytoskeletal proteins in vitro selectively induces the aggregation of highly phosphorylated proteins, such as the two larger neurofilament subunits (200 and 160 kDa) and the microtubule-associated proteins of the MAP-1 group (MAP-1A and MAP-1B). Other cytoskeletal proteins with a substantially lower phosphate content, such as the smaller neurofilament subunit (68 kDa) and tubulin, remain soluble, even in the presence of high aluminum concentrations. This suggests that aluminum interacts with phosphate groups in cytoskeletal proteins, causing their precipitation. The protein aggregates formed in the presence of aluminum are resistant to reagents such as urea and sodium dodecyl sulphate (SDS) which dissolve normal cytoskeletal polymers (neurofilaments and microtubules). These results favor the view that the neurotoxic effect of aluminum may be due primarily to the disorganization of the neuronal cytoskeleton which may occur subsequent to the precipitation of certain highly phosphorylated cytoskeletal proteins. PMID- 2109293 TI - Evidence of gonadal and gonadotropin antibodies in women with a suboptimal ovarian response to exogenous gonadotropin. AB - Failure to respond to human menopausal gonadotropin (hMG) with adequate ovarian stimulation is associated with a poor prognosis in subsequent cycles in women participating in an in vitro fertilization/embryo transfer program. Sera from 26 menstruating women (mean age 38 +/- 4.3 years) identified as "low responders" with either tubal or male factor infertility, mean baseline FSH values of 11 mIU/mL, and peak serum estradiol levels lower than 300 pg/mL were assessed for specific antibodies to human ovary and gonadotropins. Twenty-five infertile women with tubal or male factor infertility with a good response to hMG served as controls. Ninety-two percent of low responders had antibodies to FSH and 65% had antibodies to LH when assessed by enzyme-linked immunosorbent assay. Similarly, 77% of low responders had ovarian antibodies. No hepatic antibodies were found in the sera of low responders, indicating that the positivity was not a general interaction with cell components. None of the "good responders" had antibodies to gonadotropins or to ovarian or liver tissue. The significant differences in antibodies between the groups supports a possible immunologic cause for low ovarian stimulation response to gonadotropin. PMID- 2109294 TI - Umbilical cord blood gas assessment of twins. AB - Umbilical cord arterial and venous blood gas values were compared in 63 twin pairs, of which 57 pairs had birth weights of 1500 g or more each. Small differences between the first and second twins existed for PO2, PCO2, and pH. However, bicarbonate values did not differ significantly. These cord gas differences represent minor respiratory aberrations, as reflected by a tendency toward carbon dioxide retention by the second twin. Route of delivery, time interval between deliveries, and nonvertex presentations were not associated with significant deviations from these observed acid-base patterns. PMID- 2109296 TI - The equity of diagnostic related group "all payor" hospital payment and gynecology diagnostic related groups. PMID- 2109295 TI - Prenatal screening: professional standards and the limits of parental choice. AB - Medicine has a strong tradition of respect for parental autonomy in reproductive decisions. As prenatal diagnostic technology develops, the physician's obligation to the prospective parents with respect to prenatal screening must be determined, and standards for disclosure of diagnostic capabilities and results must be developed. This article explores potential justifications for limits on parental choice in prenatal screening. Information about screening capabilities can be limited appropriately when resources do not exist to ensure accurate testing and counseling. Other policy limits to parental information and choice based on risk levels, cost-benefit analyses, or harms to the parent-child relationship cannot be established without broad consensus on complex ethical issues. Limits to parental choice may be more appropriately applied through the moral values of individual physicians in their provision of diagnostic services. PMID- 2109297 TI - Tissue plasminogen activator for postvitrectomy fibrin formation. AB - The authors injected 25 micrograms of recombinant tissue plasminogen activator (tPA) into the anterior chamber or vitreous cavity of 23 eyes of 22 patients with severe intraocular fibrin formation that developed after vitrectomy surgery for complicated cases of proliferative vitreoretinopathy (PVR) (13 eyes), diabetic traction retinal detachment (TRD) (7 eyes), or endophthalmitis (3 eyes). Tissue plasminogen activator injected an average (+/- standard deviation) of 73 +/- 63 hours after vitrectomy surgery resulted in complete fibrinolysis in 21 of 23 eyes and partial fibrinolysis in one eye. The mean time to fibrin resolution was 3.0 +/- 1.0 hours. Four eyes required repeat tPA injection for recurrent fibrin formation; repeat injection resulted in complete fibrinolysis in each case. The mean follow-up duration after tPA administration was 6 months. At the final follow-up examination, the retina was totally attached in 18 of 23 eyes and was partially attached in 2. Visual acuity improved in 12 eyes (52%); it was at least 20/400 in 8. Complications of tPA injection included hyphema (2 patients) and corneal stromal thickening (2 patients). Mild, transient, periocular pain that was easily managed with non-narcotic analgesia developed in three patients. PMID- 2109298 TI - A clinicopathologic study of three carcinoid tumors metastatic to the orbit. Immunohistochemical, ultrastructural, and DNA flow cytometric studies. AB - Three patients with histopathologically proven orbital metastatic lesions from a carcinoid tumor are reported. Computed tomography (CT) disclosed a well circumscribed orbital mass in two of three cases. Each tumor was studied by both light and electron microscopy as well as immunohistochemistry and DNA flow cytometry. A review of the literature discloses the relatively rare occurrence of carcinoid tumors metastasizing to the eye and orbit. With the exception of one case, the reported metastatic carcinoid tumors to the uvea all developed from primary bronchial carcinoids. In contrast, the vast majority of the reported orbital metastases arose from ileal carcinoids. Immunohistochemical markers such as chromogranin A, synaptophysin, and serotonin have proven to be useful diagnostic tools in evaluating carcinoid tumors. Furthermore, DNA flow cytometry may be of prognostic value in patients with metastatic carcinoid tumor. PMID- 2109299 TI - Detecting and treating retinopathy in patients with type I diabetes mellitus. A health policy model. AB - Diabetic retinopathy is the major cause of new cases of blindness among working age Americans. The authors analyzed the medical and economic implications of alternative screening strategies for detecting retinopathy in a diabetic population. The approaches compared included dilated fundus examination at 6-, 12 , and 24-month intervals with and without fundus photography. Potential savings from screening and treatment are based on amounts paid by the federal government for blindness-related disability. Screening for and treating retinopathy in patients with type I diabetes mellitus was cost-effective using all screening strategies. Between 71,474 and 85,315 person years of sight and 76,886 and 94,705 person years of reading vision can be saved for each annual cohort of patients with type I diabetes mellitus when proper laser photocoagulation is administered. This results in a cost savings of $62.1 to $108.6 million. Annual examination of all diabetic patients and semi-annual examination of those with retinopathy was more effective than annual examination with fundus photography. This screening strategy is consistent with the Preferred Practice Pattern for Diabetic Retinopathy of the American Academy of Ophthalmology. PMID- 2109300 TI - Operative treatment of ankle fractures in children. AB - Fractures of the ankle (distal tibia) that involve the physis or the articular surface are one of the more common injuries for which operative treatment is indicated in children. It should be considered if accurate reduction of the articular surface, the physis, or both cannot be achieved by closed means. Operative treatment often will be required in Salter-Harris type III and IV fractures, juvenile Tillaux, and triplane fractures. PMID- 2109301 TI - Effects of acetazolamide on medullary extracellular pH and PCO2 and on ventilation in peripherally chemodenervated cats. AB - The responses of ventilation and of medullary extracellular fluid (ECF) pH and PCO2, to an intravenous (i.v.) infusion of 50 mg/kg acetazolamide (an inhibitor of carbonic anhydrase), were measured in cats anaesthetized with chloralose and urethane, in which both bilateral vagotomy and carotid nerve section had been performed. After 2 h, it was observed that: acetazolamide caused an acidosis in medullary ECF which was still developing after 2 h, reflected by a progressive fall in pH (mean = 0.215 pH units in 2 h), while ECF PCO2 showed an insignificant rise of about 1 kPa; acetazolamide caused a considerable rise in ventilation, which largely developed in the first 15 min after drug infusion; the direction of the ECF acid-base responses in the first 15 min varied, whereas that of the ventilatory response did not. Furthermore, the time course of the former developed quite differently from the latter. It was therefore concluded that the observed changes in medullary ECF pH and PCO2 can not explain the large and fast ventilatory response of acetazolamide. PMID- 2109302 TI - Cholinergic effect on rat proximal convoluted tubule. AB - The effect of cholinergic agents on proximal tubular absorption of bicarbonate and fluid were examined to investigate the possible role of the cholinergic receptor in the regulation of renal function. Proximal convoluted tubule (PCT) and peritubular capillaries were perfused with bicarbonate-Ringer's solution containing radioactive inulin. Bicarbonate (total CO2) was determined by microcalorimetry. The rates of bicarbonate absorption (JHCO3) and fluid absorption (Jv) were 143.3 +/- 7.2 pEq/min.mm and 2.52 +/- 0.23 nl/min.mm, respectively. Addition of carbachol (10(-8) M) to the capillary perfusate reduced JHCO3 by 17% and Jv by 32%. A higher dose of carbachol (10(-6) M) did not further inhibit JHCO3 or Jv. Simultaneous perfusion of atropine (10(-5) M) together with carbachol (10(-8) M) abolished the inhibitory effect of carbachol on PCT transport. Atropine itself, however, had no effect on PCT transport. The inhibitory effect of carbachol was also diminished by lanthanum chloride (10(-4) M). Carbachol (10(-6) M) had no effects from the luminal side. W-7, a calmodulin antagonist, inhibited carbachol-induced effects. Ionophore A-23187 also inhibited Jv and JHCO3. However, there was no additive effect when A-23187 and carbachol were combined in the capillary perfusate. These results suggest that there are functional cholinergic receptors on the basolateral side of the PCT that can regulate JHCO3 and Jv. Calcium influx may play a role in mediating the cholinergic effects on PCT transport. PMID- 2109303 TI - Diphenylamine-2-carboxylate (DPC) inhibits both Cl- conductance and cyclooxygenase of canine tracheal epithelium. AB - Diphenylamine-2-carboxylate (DPC) decreases Cl- conductance (GCl) in epithelia and cells of several tissues, an effect which has been ascribed to blockade of conductive Cl- channels. However, one DPC derivative, flufenamic acid, is a clinically useful non-steroidal anti-inflammatory agent, the mechanism of action of which involves the blockade of arachidonic acid metabolism by cyclooxygenase. Because GCl in canine tracheal epithelium is stimulated by exogenous prostaglandins and induction of cyclooxygenase activity, we tested the hypothesis that DPC inhibits dog tracheal epithelium GCl through inhibition of cyclooxygenase. DPC inhibited the short circuit current of amiloride-pretreated tissues by 50% at 0.138 mmol/l and by more than 95% at 3 mmol/l. Isoproterenol reversed the inhibition seen at 0.1 mmol/l DPC and stimulated current above control (indomethacin-pretreated) levels. Higher concentrations of DPC diminished the stimulation of current by subsequent exposure to isoproterenol, such that there was little effect of isoproterenol in the presence of 3 mmol/l DPC. DPC, 0.1 mmol/l, also blocked stimulation of current by exogenous arachidonic acid, but not of exogenous prostaglandins PGE or PGD. The metabolism of 3H-arachidonic acid to 3H-PGD2, monitored by HPLC, was completely blocked by 0.1 mmol/l DPC. We conclude that the isoproterenol/prostaglandin reversible blockade of GCl by DPC can be attributed to inhibition of arachidonic acid metabolism. PMID- 2109304 TI - An anticodon change switches the identity of E. coli tRNA(mMet) from methionine to threonine. AB - Recent evidence indicates that the anticodon may often play a crucial role in selection of tRNAs by aminoacyl-tRNA synthetases. In order to quantitate the contribution of the anticodon to discrimination between cognate and noncognate tRNAs by E. coli threonyl-tRNA synthetase, derivatives of the E. coli elongator methionine tRNA (tRNA(mMet)) containing wild type and threonine anticodons have been synthesized in vitro and assayed for threonine acceptor activity. Substitution of the threonine anticodon GGU for the methionine anticodon CAU increased the threonine acceptor activity of tRNA(mMet) by four orders of magnitude while reducing methionine acceptor activity by an even greater amount. These results indicate that the anticodon is the major element which determines the identity of both threonine and methionine tRNAs. PMID- 2109305 TI - Transcriptional start sites of the staphylokinase 42D promoter in E. coli and B. subtilis. PMID- 2109306 TI - Purification to homogeneity and partial amino acid sequence of a fragment which includes the methyl acceptor site of the human DNA repair protein for O6 methylguanine. AB - DNA repair by O6-methylguanine-DNA methyltransferase (O6-MT) is accomplished by removal by the enzyme of the methyl group from premutagenic O6-methylguanine-DNA, thereby restoring native guanine in DNA. The methyl group is transferred to an acceptor site cysteine thiol group in the enzyme, which causes the irreversible inactivation of O6-MT. We detected a variety of different forms of the methylated, inactivated enzyme in crude extracts of human spleen of molecular weights higher and lower than the usually observed 21-24kDa for the human O6-MT. Several apparent fragments of the methylated form of the protein were purified to homogeneity following reaction of partially-purified extract enzyme with O6-[3H CH3]methylguanine-DNA substrate. One of these fragments yielded amino acid sequence information spanning fifteen residues, which was identified as probably belonging to human methyltransferase by virtue of both its significant sequence homology to three procaryote forms of O6-MT encoded by the ada, ogt (both from E. coli) and dat (B. subtilis) genes, and sequence position of the radiolabelled methyl group which matched the position of the conserved procaryote methyl acceptor site cysteine residue. Statistical prediction of secondary structure indicated good homologies between the human fragment and corresponding regions of the constitutive form of O6-MT in procaryotes (ogt and dat gene products), but not with the inducible ada protein, indicating the possibility that we had obtained partial amino acid sequence for a non-inducible form of the human enzyme. The identity of the fragment sequence as belonging to human methyltransferase was more recently confirmed by comparison with cDNA-derived amino acid sequence from the cloned human O6-MT gene from HeLa cells (1). The two sequences compared well, with only three out of fifteen amino acids being different (and two of them by only one nucleotide in each codon). PMID- 2109307 TI - Suppression of the negative effect of minor arginine codons on gene expression; preferential usage of minor codons within the first 25 codons of the Escherichia coli genes. AB - AGA and AGG codons for arginine are the least used codons in Escherichia coli, which are encoded by a rare tRNA, the product of the dnaY gene. We examined the positions of arginine residues encoded by AGA/AGG codons in 678 E. coli proteins. It was found that AGA/AGG codons appear much more frequently within the first 25 codons. This tendency becomes more significant in those proteins containing only one AGA or AGG codon. Other minor codons such as CUA, UCA, AGU, ACA, GGA, CCC and AUA are also found to be preferentially used within the first 25 codons. The effects of the AGG codon on gene expression were examined by inserting one to five AGG codons after the 10th codon from the initiation codon of the lacZ gene. The production of beta-galactosidase decreased as more AGG codons were inserted. With five AGG codons, the production of beta-galactosidase (Gal-AGG5) completely ceased after a mid-log phase of cell growth. After 22 hr induction of the lacZ gene, the overall production of Gal-AGG5 was 11% of the control production (no insertion of arginine codons). When five CGU codons, the major arginine codon were inserted instead of AGG, the production of beta-galactosidase (Gal-CGU5) continued even after stationary phase and the overall production was 66% of the control. The negative effect of the AGG codons on the Gal-AGG5 production was found to be dependent upon the distance between the site of the AGG codons and the initiation codon. As the distance was increased by inserting extra sequences between the two codons, the production of Gal-AGG5 increased almost linearly up to 8 fold. From these results, we propose that the position of the minor codons in an mRNA plays an important role in the regulation of gene expression possibly by modulating the stability of the initiation complex for protein synthesis. PMID- 2109308 TI - Saturation mutagenesis of the Drosophila tRNA(Arg) gene B-Box intragenic promoter element: requirements for transcription activation and stable complex formation. AB - Transcription of eukaryotic tRNA genes is dependent on the A- and B-Box internal control regions (ICRs) and the upstream transcription modulatory region. The B Box ICR spans nucleotides 52 to 62 and directs the primary binding of transcription factor C as the first step in the formation of a transcription complex. The conservation of the sequence of the B-Box in all tRNA species reflects its importance in both the expression of the gene and the processing, structure and function of the gene product. In order to identify the nucleotides essential to the promoter function of the B-Box ICR, site-directed mutagenesis was used to generate all the possible single point mutations at positions 52 to 58, 61 and 62 of a Drosophila melanogaster tRNA(Arg) gene. The effect of these mutations on gene transcription was evaluated using in vitro transcription and template exclusion competition assays. Optimal activity was displayed by the wild type tDNA(Arg) B-Box sequence but several other sequences supported in vitro transcription at wild type levels. The majority of mutants, however, showed lower efficiency in the in vitro transcription assay. Of the single point mutations, those at positions 53, 55, and 56 had a critical effect on gene function in Drosophila and HeLa transcription extracts and transcription factor interaction most likely requires base contacts at these positions. Since the effect of several of the point mutations cannot be explained in terms of possible major or minor groove contributions the possibility is raised that local DNA geometry also is an important determinant in specifying B-Box function. PMID- 2109310 TI - Nucleotide sequence of Clostridium difficile toxin A. PMID- 2109311 TI - Sequence of a cDNA from the Drosophila melanogaster white gene. PMID- 2109309 TI - Isolation and characterization of a Drosophila hydei histone DNA repeat unit. AB - Histone genes in D. hydei are organized in tandemly repeated clusters., accomodating in total 120-140 repeat units. We cloned one of the repeat units and analysed the nucleotide sequence. The repeat unit has a size of 5.1 x 10(3) base pairs and contains one copy of each of the genes coding for the core histones and one copy coding for the histone H1. In the promoter regions of the genes we identified the presumptive cap sites and TATA boxes. Two additional sequence elements are shared by all five Drosophila hydei histone genes in the cluster. The sequence CCCTCT/G1 is found in the region upstream of the presumptive CAP sites. The sequence element AGTGAA occurs downstream of the presumptive cap sites and is, in contrast to the promoter element, also seen in the histone genes of Drosophila melanogaster. Cell-cycle dependent regulation of transcription of the Drosophila histone genes may be different from that in other eukaryotes since sequence elements involved in the regulation of cell-cycle dependent transcription are absent. Also other regulatory elements for transcription differ from those of other genes. The highly conserved H1-specific promoter sequence AAACACA and the H2B specific promoter sequence ATTTGCAT, which are involved in the cell-cycle dependent transcription of those histone genes in eukaryotes, are missing in the Drosophila genes. However at the 3' end of the genes the palindrome and the purine-rich region, both conserved sequence elements in histone genes of eukaryotes, are present. The spacer regions show a simple sequence organization. The silent site substitution rate between the coding regions of the D. hydei and D. melanogaster histone genes is at least 1.5 times higher for Drosophila than for sea urchin histone genes. PMID- 2109312 TI - Nucleotide sequence of the tetracycline resistance gene of pBC16 from Bacillus cereus. PMID- 2109313 TI - Nucleotide and derived amino-acid sequence of a cDNA encoding a new mouse carbonic anhydrase. PMID- 2109314 TI - Immunoglobulin heavy chain gene rearrangement involving V-V region recombination. PMID- 2109315 TI - Localization of CAI and CAII isoenzymes in normal term human placenta by immunofluorescence techniques. AB - The carbonic anhydrase isoenzymes, low activity CAI and high activity CAII, were localized in normal term human placenta by immunocytochemical techniques. Both CAI and CAII isoenzymes were present in the syncytial trophoblasts. Fetal erythrocytes in the placental capillaries also showed positive staining for both CAI and CAII isoenzymes. The possible physiological roles of CA in human placenta are also discussed. PMID- 2109316 TI - A clinicopathologic and immunohistochemical analysis of 53 cases of medulloblastoma with emphasis on synaptophysin expression. AB - Synaptophysin (SYN) has been identified as an integral membrane glycoprotein of presynaptic vesicles in neurons and neuroendocrine cells, and as a marker for medulloblastoma and other neuronal tumors. SYN expression was studied with a monoclonal antibody (MAb) by the immunoperoxidase technique in 53 medulloblastomas. The expression of neuron-specific enolase (NSE), Leu-7 (LEU), S 100 protein (S100), glial fibrillary acidic protein (GFAP), neurofilament protein (NF), vimentin (VIM), cytokeratin (CKER), and desmin (DES) was also assessed with antisera and MAbs. SYN reactivity was present in 94% of tumors, whereas reactivity with other markers of neuronal differentiation was also observed: NSE (100%) and LEU (83%). Regarding the intermediate filament proteins, 38% of the cases were reactive for VIM, 21% for GFAP, and 9% for DES; none expressed NF or CKER. Eight percent were reactive for S100. Among the 53 cases, the male-female ratio was 1:3; 80% of DES-positive tumors occurred in females. The mean age was 10.5 yr, (60% diagnosed in the first decade; peak age incidence between 5 and 10 yr). Five tumors were discovered in patients older than 20 yr of age. Follow-up showed that 40% of patients developed a recurrence and 47% of patients died of tumor. No statistically significant relationship was demonstrated between patterns of immunoreactivity and prognosis. We conclude that SYN is a useful marker for medulloblastomas, indicating that this tumor is a primitive neuronal neuroblastic neoplasm. However, it is but one of several immunophenotypic markers expressed by the medulloblastoma. PMID- 2109317 TI - Infectious and inflammatory diseases. PMID- 2109318 TI - AlgR3, a protein resembling eukaryotic histone H1, regulates alginate synthesis in Pseudomonas aeruginosa. AB - A regulatory mutation (alg52) in a Pseudomonas aeruginosa alginate-negative mutant (strain 8882) is complemented efficiently by the gene algR2 and somewhat inefficiently by a second gene termed algR3. algR3 and algR2 are located on a 4.4 kilobase-pair HindIII-BamHI fragment, which has been completely sequenced. algR2 has previously been characterized. Introduction of kanamycin-resistance cassettes and deletion-subcloning experiments involving various open reading frames in the HindIII-BamHI fragment have localized the algR3 gene, which encodes a 340-amino acid polypeptide. This highly basic regulatory protein contains 17% lysine and 36% alanine. The predicted amino acid sequence shows no significant similarity with any bacterial proteins and yet is highly similar to the sea urchin Lytechinus pictus histone H1 subtype of protein. Promoter localization by reverse transcriptase mapping of the algR3 gene shows the presence of Escherichia coli sigma 70 recognition sequences, and coupled transcription/translation experiments in E. coli demonstrate the presence of a 39-kDa polypeptide encoded by the cloned algR3 gene. PMID- 2109319 TI - Involvement of GTP-binding proteins in actin polymerization in human neutrophils. AB - The motility of human neutrophils, which is of vital importance for the role of these cells in host defense, is based on rapid and dynamic changes of the filamentous actin F-actin) network. Consequently, to understand how neutrophils move and ingest particles, we need to know how polymerization and depolymerization of actin are regulated. Previous studies by several investigators have, based on indirect evidence obtained with pertussis toxin, suggested a role for GTP-binding protein(s) (G protein) in chemotaxis-induced, but not phagocytosis-induced, reorganization of the F-actin network. The aim of the present investigation was to study the effects of directly activated G proteins (i.e., without prior ligand-receptor complex formation) on the F-actin content in human neutrophils. AlF4- induced a pronounced and sustained increase in F-actin in intact neutrophils. This effect coincided with an increase in cytosolic free Ca2+, indicating that phospholipase C and the subsequent transduction mechanism were also activated. Inhibition of phospholipase C activity by extensive depression of the cytosolic free Ca2+ level (less than 20 nM) only marginally affected the AlF4(-)-induced rise in F-actin content. The major part of the AlF4(-)-induced rise in F-actin content was also resistant to pertussis toxin, suggesting that pertussis toxin-insensitive G proteins in neutrophils are also able to trigger actin polymerization. The specificity of AlF4- in activating G proteins was also tested in permeabilized cells. In this case the effect was more rapid and could be totally abolished by guanosine 5' [beta-thio]diphosphate. In analogy, in permeabilized cells guanosine 5'-[gamma thio]triphosphate mimicked the effect of AlF4- on actin polymerization, and the effect induced by this nonhydrolyzable GTP analogue could also be totally abolished by guanosine 5'-[beta-thio]diphosphate. In summary, the present data support our previous hypothesis that G proteins are intimately linked to actin polymerization in human neutrophils. PMID- 2109320 TI - Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush. AB - Muscle plasminogen activators (PAs), such as urokinase-like PA and, to a lesser extent, tissue PA, increase dramatically after denervation induced by axotomy. The PA/plasmin system has also been implicated in degradation of specific components of the muscle fiber basement membrane after local activation of plasminogen. These results suggest that neural regulation of muscle extracellular matrix metabolism accompanies or precedes regeneration after injury and is mediated by activation of PAs. In the present study, we have used nerve crush to explore the neural regulation of muscle PA activities directly after subtotal axon interruption and during the process of reinnervation. Muscle contraction after nerve stimulation and estimation of choline acetyltransferase activity were used to monitor reinnervation. Within 24 hr of nerve crush, muscle urokinase (but not tissue PA) activity rose in soluble and membrane-bound muscle fractions, as shown by an amidolytic assay and a fibrin zymography. Membrane-bound activity was 5-fold higher than cytosol activity, but there was no shift between cellular compartments during the time course of denervation. Coincident with the return of choline acetyltransferase activity and muscle contractility, muscle urokinase returned almost to baseline levels. These results show tight regulation of muscle urokinase levels by some neural influence. PMID- 2109321 TI - Readily available fluorescein isothiocyanate-conjugated antibodies can be easily converted into targeted phototoxic agents for antibacterial, antiviral, and anticancer therapy. AB - Fluorescein-labeled antibodies have little, if any, photodynamic effect because energy acquired by light absorption is rapidly dissipated in fluorescence. However, they can be easily and efficiently converted to selective photodynamic sensitizers by iodination under mild conditions. We have outlined general experimental procedures that can be used to turn a fluorescein-labeled anti Escherichia coli antibody into a photodynamic sensitizer that selectively kills E. coli while sparing closely related Salmonella typhimurium. These results demonstrate that iodination did not destroy the specificity or activity of the antibody. This technique should be applicable to the large number of fluoresceinated antibodies that are commercially available. Thus, this strategy provides a simple way to rapidly prepare a large number of targeted phototoxic agents that can be used for the selective destruction with light of nearly any type of tissue or organism. PMID- 2109322 TI - The second zinc-finger domain of poly(ADP-ribose) polymerase determines specificity for single-stranded breaks in DNA. AB - Poly(ADP-ribose) polymerase (EC 2.4.2.30) is a zinc-binding protein that specifically binds to a DNA strand break in a zinc-dependent manner. We describe here the cloning and expression in Escherichia coli of a cDNA fragment encoding the two putative zinc fingers (FI and FII) domain of the human poly(ADP-ribose) polymerase. Using site-directed mutagenesis, we identified the amino acids involved in metal coordination and analyzed the consequence of altering the proposed zinc-finger structures on DNA binding. Disruption of the metal binding ability of the second zinc finger, FII, dramatically reduced target DNA binding. In contrast, when the postulated Zn(II) ligands of FI were mutated, the DNA binding activity was only slightly affected. DNase I protection studies showed that the FII is involved in the specific recognition of a DNA strand break. These results demonstrate that poly(ADP-ribose) polymerase contains a type of zinc finger that differs from previously recognized classes in terms of both structure and function. PMID- 2109323 TI - Diphtheria toxin and its ADP-ribosyltransferase-defective homologue CRM197 possess deoxyribonuclease activity. AB - The cytotoxic mechanism of diphtheria toxin (DTx) is associated with its ability to inhibit protein synthesis by ADP-ribosylation of elongation factor 2. Although DTx intoxication leads to internucleosomal DNA cleavage and cell lysis, these events do not occur when protein synthesis is inhibited by alternative treatments (e.g., cycloheximide). Here we show that endonucleolytic degradation of DNA is an intrinsic activity of DTx and also of the crossreactive mutant protein CRM197. Assays using DNA-impregnated gels as well as linear and supercoiled DNA in solution revealed not only that CRM197 has nuclease activity but also that its specific activity is actually significantly greater than that of the wild-type molecule. Since CRM197 contains a single amino acid substitution that renders it incapable of ADP-ribosylation, we propose that the active sites for ADP ribosyltransferase and nuclease activities are distinct. PMID- 2109324 TI - RTA, a candidate G protein-coupled receptor: cloning, sequencing, and tissue distribution. AB - Genomic and cDNA clones, encoding a protein that is a member of the guanine nucleotide-binding regulatory protein (G protein)-coupled receptor superfamily, were isolated by screening rat genomic and thoracic aorta cDNA libraries with an oligonucleotide encoding a highly conserved region of the M1 muscarinic acetylcholine receptor. Sequence analyses of these clones showed that they encode a 343-amino acid protein (named RTA). The RTA gene is single copy, as demonstrated by restriction mapping and Southern blotting of genomic clones and rat genomic DNA. Sequence analysis of the genomic clone further showed that the RTA gene has an intron interrupting the region encoding the amino terminus of the protein. RTA RNA sequences are relatively abundant throughout the gut, vas deferens, uterus, and aorta but are only barely detectable (on Northern blots) in liver, kidney, lung, and salivary gland. In the rat brain, RTA sequences are markedly abundant in the cerebellum. RTA is most closely related to the mas oncogene (34% identity), which has been suggested to be a forebrain angiotensin receptor. We cannot detect angiotensin binding to the RTA protein after introducing the cognate cDNA or mRNA into COS cells or Xenopus oocytes, respectively, nor can we detect an electrophysiologic response in the oocyte after application of angiotensin peptides. We conclude that RTA is not an angiotensin receptor; to date, we have been unable to identify its ligand. PMID- 2109325 TI - Somatic diversification of chicken immunoglobulin light chains by point mutations. AB - The light-chain locus of chicken has 1 functional V lambda 1 gene, 1 J gene, and 25 pseudo-V lambda-genes (where V = variable and J = joining). A major problem is which somatic mechanisms expand this extremely limited germ-line information to generate many different antibodies. Weill's group [Reynaud, C. A., Anquez, V., Grimal, H. & Weill, J. C. (1987) Cell 48, 379-388] has shown that the pseudo-V lambda-genes diversify the rearranged V lambda 1 by gene conversion. Here we demonstrate that chicken light chains are further diversified by somatic point mutations and by V lambda 1-J flexible joining. Somatic point mutations were identified in the J and 3' noncoding DNA of rearranged light-chain genes of chicken. These regions were analyzed because point mutations in V lambda 1 are obscured by gene conversion; the J and 3' noncoding DNA are presented in one copy per haploid genome and are not subject to gene conversion. In rodents point mutations occur as frequently in the V-J coding regions as in the adjacent flanking DNA. Therefore, we conclude that somatic point mutations diversify the V lambda 1 of chicken. The frequency (0-1%) and distribution of the mutations (decreasing in number with increased distance from the V lambda 1 segment) in chicken were as observed in rodents. Sequence variability at the V lambda 1-J junctions could be attributed to imprecise joining of the V lambda 1 and J genes. The modification by gene conversion of rearranged V lambda 1 genes in the bursa was similar in chicken aged 3 months (9.5%) or 3 weeks (9.1%)--i.e., gene conversion that generates the preimmune repertoire in the bursa seems to level off around 3 weeks of age. This preimmune repertoire can be further diversified by somatic point mutations that presumably lead to the formation of antibodies with increased affinity. A segment with structural features of a matrix association region [(A + T)-rich and four topoisomerase II binding sites] was identified in the middle of the J-C lambda intron (where C = constant). PMID- 2109326 TI - Superstructure of the Drosophila ribosomal gene family. AB - Determining the spatial organization of middle repetitive DNA has proven difficult for several reasons. Repeated arrays are often so large that molecular methods alone cannot resolve their organization, and the lack of phenotypic markers within arrays limits the value of classical genetic analysis. We have characterized the superstructure of one repeated gene family, the ribosomal gene family of Drosophila melanogaster, by a combination of recombinational and molecular analyses of spacer-length variants. The resulting genetic maps demonstrate that some spacer variants are widely dispersed, while others are limited in their distribution. Moreover, exchange among ribosomal DNA (DNA encoding rRNA) arrays was often unequal, leading to a prediction of little or no relationship between physical location in an array and relatedness of gene family members. Extensions of our procedure may be generally useful for mapping the superstructure of repetitive DNA. PMID- 2109327 TI - Flavor preferences conditioned by intragastric polycose infusions: a detailed analysis using an electronic esophagus preparation. AB - The present series of experiments examined the rat's conditioned preference for flavors associated with intragastric (IG) Polycose infusions. Adult female rats were fitted with two chronic intragastric catheters and were trained to drink flavored water (CS+; e.g., cherry-water) paired with IG infusions of 32% Polycose. On alternate days a different flavor (CS-; grape-water) was paired with IG water infusions. The flavored water and chow were available 23 hr/day. In subsequent two-choice tests the rats displayed strong preferences for the CS+ flavor (up to 98%). The CS+ preference persisted for several weeks during extinction tests when both the CS+ and CS- were paired with IG water or with no infusions. The rats also preferred the CS+ to plain water which contrasts with the mild aversion naive rats display to the flavored water. The acquired preference for the CS+ flavor was not as strong, however, as the rats' innate preferences for the taste of saccharin or Polycose. Also, unlike their response to saccharin and Polycose, the rats' acceptance (absolute intake) of the CS+ flavor was not elevated. CS+ intake was increased, though, when saccharin was added to the flavored water. The rats reversed their flavor preference when the reinforcement contingencies were reversed. Also, in the absence of unique flavor cues, the rats learned to prefer, apparently based on somatosensory cues, the sipper tube that was paired with IG Polycose infusions. The effects of flavor and IG Polycose infusions on drinking patterns and caloric intake are also described. PMID- 2109328 TI - Amniotic fluid ingestion enhances opioid-mediated but not nonopioid-mediated analgesia. AB - Ingestion of amniotic fluid or placenta by rats has been shown to enhance several types of opioid-mediated analgesia: that induced by morphine, footshock, vaginal/cervical stimulation, and late pregnancy. This enhancement has also been blocked by administration of opioid antagonists. The present study was designed to examine further the specificity of the enhancement effect for opioid-mediated analgesia by testing for enhancement following administration of aspirin, a nonopioid analgesic. The formalin test was used as the pain threshold assay. Amniotic fluid or beef bouillon was administered by orogastric tube to rats that were treated either with morphine sulfate or saline, or pretreated with naltrexone, then treated with aspirin or vehicle. Both morphine and aspirin treatments produced analgesia. Amniotic fluid significantly enhanced the analgesia produced by morphine, but did not enhance the analgesia produced by aspirin, further suggesting that the enhancing effect of amniotic fluid ingestion is specific for opioid-mediated analgesia, such as that existing at the start of parturition. PMID- 2109329 TI - V-Y advancement flaps in the reconstruction of skin defects of the posterior heel and ankle. AB - A V-Y advancement pedicle flap including fascia has been used for reconstruction of soft-tissue defects of the posterior heel and ankle region. This flap has been used to cover 17 defects in 16 patients ranging in age from 4 to 58 years, and results have been good. We limited this application to patients without systemic disease and under 60 years of age and did not apply it to the elderly, debilitated, or systemic vascular damaged patients. There were no complications or loss of overlying skin, with the exception of one superficial tip necrosis of the flap. The results indicate the reliability and usefulness of this procedure in coverage of the posterior heel and ankle regions. It is a relatively quick and simple procedure that is without a free skin graft, and it involves only one stage that adequately corrects the skin defect at the posterior heel and ankle without prolonged splintings and results in negligible deformity of the donor site. PMID- 2109330 TI - Specific sensitivity of patients with panic attacks to carbon dioxide inhalation. AB - One inhalation of 35% CO2 in oxygen was administered to 36 patients with anxiety disorders and 14 healthy controls. Eighteen patients had a diagnosis of panic disorder (PD) and 18 of obsessive-compulsive disorder (OCD). As a placebo control for CO2, compressed air was administered in a double-blind design. Immediately before and after the inhalation, levels of anxiety and DSM-III-R symptoms of panic were assessed. CO2 elicited high levels of subjective anxiety in the PD group. Patients with OCD were hardly affected by the inhalation, and did not differ from healthy controls. These results suggest that CO2 challenge should be considered as a specific probe for subjects with panic-anxiety. It is speculated that CO2 may trigger some as yet undefined mechanisms, possibly linked to ventilation control, which demarcate panic from other types of pathological anxiety. PMID- 2109331 TI - Endocrine aspects of mitochondrial cytopathy: marked phenotypic variation in two affected siblings. AB - Two siblings with 'mitochondrial myopathy', one of whom was found to have hypergonadotrophic hypogonadism whilst the other had normal endocrine function are reported. The inheritance suggests an autosomal recessive mode. The protean manifestations of the disorder are emphasized. Attention is drawn to the possible association of endocrine abnormalities in addition to the more widely recognized neuromuscular signs. PMID- 2109332 TI - Rural/urban differences of diabetes--impaired glucose tolerance, hypertension, obesity, glycosolated haemoglobin, nutritional proteins, fasting cholesterol and apolipoproteins in Fijian Melanesians over 40. AB - Two populations of Fijian Melanesians over 40 years of age were compared. The first population was located in a remote rural area and the other in an urban environment. There was no significant difference between the two populations in age, height and diastolic blood pressure. Highly significant differences were observed in mean weight, body mass index, prevalence of impaired glucose tolerance, prevalence of diabetes, mean glycosolated haemoglobin, mean systolic blood pressure, fasting cholesterol, immunological albumin, immunological transferrin, and A1 and B apolipoproteins. The higher value was associated with urban living. Thus urban living is associated with obesity, impaired glucose tolerance, diabetes, higher systolic blood pressure, higher levels of fasting lipids and increased risk factors for cardiovascular disease. PMID- 2109333 TI - The evolution of acute renal failure, 1956-1988. AB - A total of 1347 patients with severe acute renal failure, treated at a single centre between 1956 and 1988, are reviewed. Only patients with an acute uraemic episode requiring dialysis and/or with serum creatinine levels above 600 mumols/l were included. The age of patients increased from median 41.25 years in the 1950s to 60.5 years in the period 1980 to 1988. The case-mix also altered with a decline in obstetric and traumatic disease, both of which carried an excellent prognosis, and an increase in the number of elderly patients with complicated medical and surgical conditions. Survival significantly decreased with increasing age and in the presence of complicating factors such as sepsis or malignancy. Despite these changes, there has been a progressive improvement in survival from 48.8 per cent in 1956-1959 to 57.9 per cent in 1985-1988. Survival for medical and surgical cases has improved from 38.5 per cent in 1956-1959 to 57.9 per cent in 1985-1988 (overall survival for non-obstetric cases was 44.2 per cent), due to improved prognosis for acute renal failure in general and acute renal failure due to intrinsic renal disease in particular. PMID- 2109334 TI - [Intramural pseudodiverticulosis of the esophagus]. AB - Esophageal intramural pseudodiverticulosis is a rare condition of yet unknown etiology. Histologic findings of pseudodiverticulosis are characterized by dilated submucosal mucous glands in the esophagus wall. The clinical features including slowly progressive dysphagia mimic those of esophageal carcinoma. The diagnosis is established by radiologic examination, revealing numerous tiny outpouchings of the esophagus wall filled with contrast material. Endoscopic biopsy of the frequently associated stenosis of the upper esophagus is mandatory. Computer tomography shows localized thickening of the esophagus wall. Manometry reveals motoric dysfunction. Etiology and therapeutic management are discussed. PMID- 2109335 TI - Morphine-augmented hepatobiliary scintigraphy in the severely ill: caution is in order. AB - Morphine augmentation in hepatobiliary scintigraphy has been reported as a useful tool to shorten imaging time. The technique has not been extensively evaluated in patients who are severely ill and receiving total parenteral nutrition, although the study of these patients with non-morphine-augmented hepatobiliary scintigraphy is problematic. The authors retrospectively analyzed 51 morphine augmented hepatobiliary studies performed in a tertiary referral center on a population with a high proportion of severe intercurrent illness (18 patients, 14 of whom were receiving total parenteral nutrition) and hepatocellular dysfunction (eight patients). The overall sensitivity was 94%, specificity was 69%, and the false-positive rate was 40% for the diagnosis of acute cholecystitis. The majority of the false-positive cases occurred in the severely ill subgroup (false positive rate, 60%). Morphine-augmented hepatobiliary studies may be advantageous because of shortened imaging time. However, patients who have severe intercurrent illness, whether or not they are receiving total parenteral nutrition, have a higher frequency of false-positive morphine-augmented hepatobiliary studies, and positive findings at scintigraphy in this patient group should be interpreted with caution. PMID- 2109336 TI - Monitoring therapy with a gonadotropin-releasing hormone analog: utility of MR imaging. AB - The utility of magnetic resonance (MR) imaging in assessing response to therapy with a gonadotropin-releasing hormone (GnRH) analog was assessed in 19 women with uterine leiomyomas and 19 women with endometriosis. There was a significant reduction in individual fibroid volumes at 3 months (P less than .05) and at 6 months (P less than .005) in the drug group, whereas there was no significant change in the placebo group. Vessel conspicuity significantly decreased at 3 months (P less than .02) and at 6 months (P less than .01) in the drug group but not in the placebo group. In the patients with endometriosis, there was a significant decrease (P less than .0006) in the number of endometriomas visualized. Significant changes were also noted in the pelvis in women who were receiving the GnRH analog. After 6 months of therapy, the identifiability of the ovaries was significantly poorer (P less than .05). The authors conclude that the utility of conservative therapy with a GnRH analog can be quantitatively assessed with MR imaging. PMID- 2109337 TI - Role of acetylcholine, histamine and gastrin in the acid response to intracisternal injection of TRH analog, RX 77368, in the rat. AB - The role of gastrin, acetylcholine and histamine in the acid response to central vagal activation induced by intracisternal injection of the stable analog, RX 77368, was further investigated in urethane-anesthetized rats with gastric fistula. The gastrin monoclonal antibody 28-2 injected intravenously, at a dose previously shown to prevent gastrin-induced stimulation of acid secretion, did not alter the peak acid response to intracisternal injection of RX 77368 (15 ng). The TRH analog (30 ng) injected into the cisterna magna increased levels of histamine measured in the hepatic portal blood. Cimetidine administered at a dose which completely blocked the stimulation of gastric acid secretion produced by intravenous infusion of histamine, inhibited by 62% the stimulatory effect of intracisternal RX 77368 (30 ng). The M1 muscarinic antagonist, pirenzepine, completely prevented the acid secretion induced by intracisternal RX 77368 (30 ng). These results indicate that the acid response to central vagal activation by the TRH analog in rats involved M1 muscarinic receptors along with histamine release acting on H2 histaminergic receptors whereas gastrin does not appear to play an important role. PMID- 2109338 TI - Thyrotropin-releasing hormone stimulates intestinal transit in young rats. AB - The effect of intracisternal injection of thyrotropin-releasing hormone (TRH) on small intestinal transit of a charcoal bolus was investigated in 14-, 21-, 28- and 35-day-old and adult rats. Intracisternal TRH (15 micrograms in 2 microliters) was administered, and transit (distance traveled by the charcoal) was measured 120 min later. In all age groups, intracisternal TRH increased charcoal transit significantly (P less than 0.05) as compared to saline-treated controls. This increase in transit was not mimicked by intravascular TRH, and it was blocked in all age groups by prior intraperitoneal injection of atropine (2 micrograms/g body weight). Vagotomy blocked TRH-induced increases in small intestine transit in rats of 28 days and older. Prior intraperitoneal injection of the antiserotonin compound, cyproheptadine (1 microgram/g body weight) reduced TRH-induced increases in small intestine transit in all age groups. These results demonstrate that centrally administered TRH stimulates small intestine transit through both cholinergic and serotonergic mechanisms in rats as early as 14 days of age. PMID- 2109339 TI - Effect of thyrotropin-releasing hormone on immune functions of peripheral blood mononuclear cells. AB - The tripeptide thyrotropin-releasing hormone (TRH) works as a hypothalamic hormone, but is found also outside the brain in intrinsic nerve fibers of the gastrointestinal tract. There is evidence that TRH modulates the activity of immunocompetent cells, although there are only very few data on TRH-mediated immune effector functions. Since we could recently show that TRH inhibits monocyte activities we were also interested in other possible TRH modulated immune functions. Peripheral blood mononuclear cells (PBMC) from ten healthy subjects were cultured for 7 days and pulsed with 0.125 and 0.250 microgram/ml Pokeweed mitogen (PWM). 10(-12) to 10(-6) M TRH was added simultaneously with PWM. Lymphocyte proliferation [(3H]thymidine incorporation), interferon-gamma (IFN-gamma) activity (RIA) and immunoglobulin activities (IgG, IgM, IgA; ELISA) were determined in the supernatants. We could demonstrate a TRH-dependent decrease in PWM-pulsed IgG activity with significant (alpha = 0.05) values at 10( 8) and 10(-10) M (-29 +/- 6%/-16 +/- 3% for PWM 0.125 microgram/ml and -17 +/- 9%/-11 +/- 9% for PWM 0.250 microgram/ml). This inhibitory effect could be abolished by an anti-TRH antiserum. There was no TRH effect on IgM and IgA activities, IFN-gamma activity and lymphocyte proliferation compared with the PWM stimulated values alone. The described TRH effect on the polyclonal IgG response by PBMC gives further evidence for a functional link between the immune system and the endocrine system, although its underlying mechanism is not yet clear. PMID- 2109340 TI - Systemic administration of kainic acid produces elevations in TRH in rat central nervous system. AB - Several studies have suggested that the concentration of thyrotropin releasing hormone (TRH) in the central nervous system (CNS) is influenced by the level of CNS activation. Hibernation in the ground squirrel and estivation in the lungfish result in region-specific decreases in TRH concentrations. Repeated electroconvulsive shock (ECS) and amygdaloid kindling have been shown to result in elevations of TRH in limbic brain regions. In the present study, limbic seizures induced by systemic administration of kainic acid resulted in substantial increases in the TRH content of posterior cortex and of dorsal and ventral hippocampus, and in moderate elevations in anterior cortex, amygdala/piriform cortex and corpus striatum. Maximal elevations in TRH were observed 2-4 days after kainic acid administration, and by 14 days TRH levels were similar to control values, with the exception of the dorsal hippocampus, which exhibited more prolonged elevations in TRH levels. Prior exposure to limbic seizure activity attenuated the magnitude of TRH elevation in response to a second administration of kainic acid in the posterior cortex but in no other region. These results indicate that seizure-related processes or events influence TRH systems in the CNS. Neuronal populations involved in limbic seizure induced damage may be involved in the modulation of posterior cortical TRH levels. PMID- 2109341 TI - [A study on LH- and FSH-RIA kits by immunoradiometric assay]. AB - An evaluation of LH- and FSH-RIA BEAD kits based on IRMA was carried out. The results obtained with the methods characterized by the use of monoclonal antibodies, i.e., one is linked to solid phase, and another is isotopically labeled, were compared with those determined by the Daiichi LH- and FSH-kits. Intra- and inter-assay precision, recovery, linearity, and specificity of both methods were favorable without exceptions. The cross reactivity of the LH kit to 5,000 mIU/ml hCG revealed within the range of less than 3 mIU/ml. Significant correlations were observed between the results derived from conventional Daiichi LH- and FSH-kits. The results from the conventional kits exhibited 30 to 40% of those from the Daiichi kits, considered to be mainly due to the difference in standard calibrations used. Among the individuals within the normal menstrual cycle, the serum LH- and FSH-levels determined by the present kits gave a typical pattern with a peak in the preovulatory phase. On the other hand, the LH- and FSH values of individuals in normal pregnancy revealed strikingly decreased in comparison with those of non-pregnant women. PMID- 2109342 TI - [Topical nitroglycerin to facilitate peripheral venous cannulation]. PMID- 2109343 TI - Effect of chronic oral delorazepam on in vitro and in vivo hepatic drug metabolizing enzyme activities in the rat. AB - In vivo (delorazepam clearance) and in vitro (monooxygenase activity markers) alterations in drug metabolism and the extent of enzyme induction of the hepatic cytochrome P-450 system were evaluated after oral administration of delorazepam (2.5, 25 and 150 mg/kg) for two weeks to male Sprague-Dawley rats. This benzodiazepine had no significant effect on drug metabolizing enzymes, except for slight enhancement of in vitro aniline p-hydroxylase activity which occurred at doses approximately 100 times those used clinically (0.5-2 mg). Under the likely conditions of exposure to delorazepam in human therapy therefore, such alteration in liver enzymes would be unlikely to have clinical relevance. PMID- 2109344 TI - Macrophage activity in rabies virus infection of genetically selected high and low antibody responder lines of mice. AB - After infection with the Pasteur strain of fixed rabies virus, the onset of disease, mortality, interferon (IFN) synthesis and interaction of the virus with macrophages were investigated in high (HI) and low (LI) antibody responder lines of mice. The HI mice were shown to be more resistant than the LI mice, and resistance was age-dependent, since mice from both mouse lines were fully susceptible up to 2 weeks of age. IFN synthesis studies of the serum indicated that, after rabies infection, HI mice produced a slightly higher amount of IFN, which was determined to be predominantly IFN-gamma. In the brains of LI mice, only IFN-alpha/beta was found, in contrast to the mixture of IFN-alpha/beta and IFN-gamma observed in the brains of HI mice. Although macrophages from the two mouse lines expressed the same degree of extrinsic activity, their intrinsic activities were quite different; the LI mice showed a greater ability to uptake and process the virus or ingest C3 (IgM) sheep red blood cells. The present findings attribute the higher antibody response and IFN-gamma synthesis observed in HI mice during rabies infection to slower processing of the rabies antigen in their macrophages, thus conferring upon them a greater ability to present it to the immune system, leading to a higher degree of resistance to rabies infection. PMID- 2109346 TI - Potassium channels in excitable and non-excitable cells. PMID- 2109345 TI - [IgM myeloma: 6 cases and a review of the literature]. AB - IgM myeloma is a rare plasma cell neoplasia, with an estimated incidence of 0.5% in patients with myeloma. Approximately, between 2 and 3.3% of IgM monoclonal gammopathy are IgM myeloma. Six unpublished cases of IgM myeloma, association of an IgM monoclonal gammopathy and an exclusive plasma cell neoplasia, are reported. Forty-six other cases have been found in the literature. The initial clinical characteristics of these patients are: sex-ratio of 1.1, mean age of 62 years, fatigue in 95% of the cases, bone pain in 80%, osteolytic lesions in 78%, fever in 13%, hepatomegaly and splenomegaly in 8%, lymphadenopathy in 10%, hemorrhagic diathesis in 35% and neurologic involvement in 18%. Initial biological features are: anemia in 62% of the cases, creatininemia greater than 20 mg/l in 10%, calcemia greater than 120 mg/l in 24%. Mean serum IgM level is 33 g/l, mean medullary plasmocytosis is 52%. 80% of the patients presented with IgM kappa and only 20% with IgM lambda. Proteinuria with light chains are found in 65%. One-year survival is estimated at 82%, 2-year at 62%, 3-year at 46% with a median of 30 months. No prognostic factor is found. IgM myeloma with characteristics of both myeloma and macroglobulinemia appears well individualized among B-cell neoplasia. However, the distinction between Waldenstrom's macroglobulinemia and IgM myeloma can be difficult in case of lympho-plasmocytic bone marrow proliferation with osteolytic lesions. PMID- 2109347 TI - [Nutrition, metabolic and endocrine complications during extrarenal dialysis]. AB - Patients with chronic renal failure treated by maintenance dialysis often have nutritional disorders, metabolic disorders concerning lipids, proteins and carbohydrates, and disorders of endocrine systems involved in the regulation of these metabolisms. These disorders are difficult to diagnose, as their clinical symptoms are few and of little pathognomonic value. Hence the need for anthropometric measurements as well as biochemical and physiological exploration of metabolic pathways for intermittent overall evaluation and longitudinal follow up. These patients have reduced subcutaneous fat reserves, intolerance to carbohydrates by resistance to insulin (partially corrected by haemodialysis), low levels of plasma aminoacids, notably valine, type IV hyperlipidaemia with low levels of essential fatty acids, fragile immune system and increased requirements for vitamins B, especially B6. Dietary recommendations include: food energy 35 kiloCal/kg bodyweight/day; proteins 1 to 1.2 g/kg bodyweight/day (50 p. 100 of which must be complete proteins) and supplements of vitamins. Dialysis must be optimal for clearance of nitrogen compounds and body homeostasis. PMID- 2109348 TI - Glass ionomers in proximal cavities of primary molars. AB - Proximal cavities with or without a dovetail were prepared in primary molars of 5 7-yr-old children. The cavities were filled with either a traditional glass ionomer (Ketac-Fil) or a cermet (Ketac-Silver). A total number of 199 treated teeth were available for evaluation 5-14 months after placement of the fillings. The percentage of success was 84% for Ketac-Fil and 77% for Ketac-Silver. There was no clear difference in rate success between the two different types of cavities. PMID- 2109349 TI - Effect of disinfecting solutions on surface texture of alginate and elastomeric impressions. AB - The effect of immersion in six disinfecting solutions on the surface texture of 10 impression materials was investigated. Assessment of the surface texture was based on measurement of the ability to reproduce fine detail. Impressions were taken of a roughness standard, i.e. a steel block with known roughness. After setting, the impressions were either stored at room temperature for 24 h, for control, or immediately immersed in a disinfecting agent for 60 min (in one case 10 min), and after 24 h poured with gypsum. After another 24 h, the roughness of the dies was recorded with a profilometer. Three addition-curing silicones were left unaltered by disinfection. For the remaining seven materials, the ability of detail reproduction was changed for some of the combinations of impression material and disinfecting solution. In general, this meant a reduction of detail reproduction, but occasionally an improvement of the surface texture resulted from disinfection. Changes in surface texture were most often brought about by a solution of chlorinated trisodium phosphate. It was concluded that elastomeric impression materials reproduced fine detail better than did alginates and that both types of impression material may be immersed in specific disinfecting solutions for as long as 1 h without the surface texture being impaired. PMID- 2109350 TI - Elevated thyroxine and free thyroxine in euthyroid patients: familial dysalbuminemic hyperthyroxinemia. AB - An eleven year old male was evaluated because of persistent elevation of thyroxine levels and elevated thyroxine index calculated as "T7" but normal thyrotropin levels. The findings were demonstrated by thyroxine binding protein electrophoresis to be due to aberrant thyroxine binding to albumin. The abnormality was also documented in the patient's father. This entity, known as familial dysalbuminemic hyperthyroxinemia, is being reported with increasing frequency and should be suspected when elevated total thyroxine and free thyroxine or "T7" levels are associated with a normal thyrotropin level. The case reported is somewhat unusual in that the triiodothyronine affinity of the aberrant protein appears to be more pronounced than usually reported with this syndrome and the corresponding total triiodothyronine level was significantly elevated. PMID- 2109351 TI - A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons. AB - A genomic clone encoding the Purkinje cell-specific L7 protein has been isolated and utilized to drive the expression of beta-galactosidase in mice. Three independent transgenic lines, germ line transformed with an L7-beta-galactosidase fusion gene, exhibit beta-galactosidase expression in both cerebellar Purkinje cells and retinal bipolar neurons. This distribution is the same as that previously determined for the L7 protein by immunohistochemistry. The transgenic murine lines can be used to obtain populations of marked Purkinje and bipolar neurons. Similar L7 promoter constructs can be used to express other foreign genes specifically in these two classes of neurons. PMID- 2109352 TI - Bone formation following carpal interposition arthroplasty. AB - Two cases of bone formation occurring at the site of carpal excision and soft tissue interposition are presented. PMID- 2109353 TI - Screening for scoliosis. A cost-effectiveness analysis. AB - The cost-effectiveness of three different screening methods was studied: the no specific screening, the conventional clinical screening, and the combined clinical moire screening alternative. A multistage model of the treatment process was developed. Data from retrospective studies in Malmo were used. The costs for health care and production loss were calculated and applied to the time profiles of the three screening alternatives. Health care costs as well as costs in loss of production increased with the introduction of the conventional clinical screening program. However, when the clinical screening was combined with the moire technique, the costs were markedly reduced. Thus, the combined clinical moire screening would be the cost-effective way of using resources to prevent scolioses from developing into a more severe deformity. PMID- 2109354 TI - Radiotherapy in emergency treatment of malignant exophthalmos. AB - 18 patients with severe Graves' ophthalmopathy were treated with retrobulbar irradiation. 14/18 (78%) had at least a satisfactory immediate result to the radiotherapy, and every fourth patient had a good late result with normal eyes. A total depth dose of about 4000 cGy, with about 350 cGy daily fraction dose, and a total depth dose of about 2000 cGy, with about 200 cGy daily fraction dose, gave equal immediate and late results according to the exophthalmos. One patient lost her vision and is discussed in detail in the light of the literature. PMID- 2109355 TI - Response of postmastectomy lymphangiosarcoma to radiotherapy: report of four cases. AB - We have reported on four previously unpublished cases of postmastectomy lymphangiosarcoma. All of these cases had suffered from a long-lasting lymphedema of the upper extremity. Only one patient had survived over one year. After radiotherapy she lived four years from first lesion of lymphangiosarcoma. She died locally disease-free in spite of two earlier recurrences, which were also treated with radiotherapy. We believe that only in early cases can the radiotherapy give a good palliation in postmastectomy lymphangiosarcoma. PMID- 2109356 TI - [Intraoperative radiotherapy (IORT) at the Graz University Clinics: development and dosimetry of an applicator system]. AB - The use of high energy electron beams for intraoperative radiotherapy necessitates special technical adjustments of the conventional megavolt equipment. At the University Clinic of Radiology, Division of Radiotherapy in Graz, an applicator system for electron energies up to 20 MeV and cone diameters up to 14 cm was developed. A self modified commercial operating table was used instead of the treatment couch to guarantee optimum mobility for the docking maneuver. The technical set-up of this adaptor system as well as the dosimetric considerations and calculations will be presented in detail. PMID- 2109357 TI - [Development of special electron applicators for intraoperative radiotherapy at the Grosshadern Clinic]. AB - A specialized applicator system for intraoperative radiation therapy using high energy electrons of a linear accelerator has been developed and manufactured, regarding the specific situation that there is no dedicated linear accelerator available at the surgery facility. Additionally, long lasting interruptions of the daily routine irradiations are hardly tolerable. A significant improvement of the procedure could be achieved developing applicators, which are divided into two halves. Positioning the lower part of the applicator into the patient at the operating room already, the transportation and the irradiation of the closed patient is possible. Adapted to the linear accelerator in use, a Siemens Mevatron KD having electron energies in the range from 6 to 21 MeV, the dosimetric properties of the system have been optimized by iteration. Excess dose values near the applicator walls could be avoided completely. A rapid decrease of the leakage dose could be realized. PMID- 2109358 TI - Radiobiological intercomparison of two clinical neutron beams using the regeneration of mouse intestinal crypts. AB - Determination of dose modification factor greatly facilitates the introduction of clinically proven neutron therapy schedules at new installations. We have compared the biological performance of the p(66)+Be neutron facility at Faure, South Africa, with the established p(65)+Be installation at Louvain-la-Neuve, Belgium. Filtration, D gamma/DT, dose rate and HVT 5/15 for the Louvain and Faure beam are: 2 cm, 2.5 cm polyethylene; 3%, 5%; 0.2 Gy/min, 0.4 Gy/min; and 20 cm and 19 cm respectively. Dosimetry was done in A-150 plastic. Irradiation of BALB/C mice was carried on according to the dose accumulation method in a perspex phantom at 5 cm depth and at an SSD of 150 cm at a field size of 28 X 28 cm2. Sections of the jejunum were prepared at each centre and analyzed by both. The RBE of the Faure beam determined at a survival level of 50 crypts ranged from 1.64 to 1.69. The dose modification factor RBE of the Louvain beam given by Beauduin et al. was 1.61 +/- 0.14. The dose modification factor of the Faure beam relative to the Louvain beam is thus 1.03 +/- 0.13 which could be expected from the similarity of the physical characteristics. Independent RBE measurements in a variety of systems also suggest similar biological properties. The depth variation of the RBE was found to be 4% (mouse gut) using 3 cm polyethylene filter over the depth range of 2.5 to 13.5 cm. This is in agreement with microdosimetry measurements using polyethylene filters of various thicknesses and with V79 measurements reported by Slabbert et al. PMID- 2109359 TI - [Dark times in Tromso. Interview by Kjell Arne Bakke]. PMID- 2109360 TI - [Nothing new from the Northern frontier]. PMID- 2109361 TI - [Burned-out nurse administrator gives up. Interview by Kjell Arne Bakke]. PMID- 2109362 TI - [Shoemakers should stick to their lasts. Interview by Bjorn Arild Ostby]. PMID- 2109364 TI - [Salary negotiations: finally profitable for nurses?]. PMID- 2109363 TI - [Model station on the way down?]. PMID- 2109365 TI - [Men at their best]. PMID- 2109366 TI - [Miriam is free!. Interview by Ojvind Kyro]. PMID- 2109367 TI - [Vaccination Project-88. New Norwegian vaccine against type B meningitis--what happened?]. PMID- 2109368 TI - [Pensioner on AIDS duty. Interview by Siv Barstad Heide]. PMID- 2109369 TI - [Regional Hospital in Tromso]. PMID- 2109370 TI - [Hospital administrator cleaning up?. Interview by Kjell Arn Bakke]. PMID- 2109371 TI - The combined effects of N-3 fatty acids and aspirin on hemostatic parameters in man. AB - Both fish oils and aspirin are readily available to the consumer as over-the counter preparations. Since both of these products have been shown to prolong bleeding times, it is possible that hemostasis might be adversely affected in subjects taking them in combination. This study was undertaken to examine the effects of n-3 fatty acids and aspirin on platelet function. Eight healthy men took a total of 485 mg of aspirin over 3 days before beginning two weeks of fish oil supplementation (4.5 g of n-3 fatty acids/day). Subjects continued with fish oil while resuming aspirin treatment for 3 days. Aspirin alone prolonged bleeding times by 34% (p less than 0.05). Fish oil alone raised bleeding times only slightly (9%; N.S.), but aspirin plus fish oil raised them by 78% (p less than 0.01). The increase in bleeding times with the combination (78%) was not significantly different than the sum of the individual increases (43%). The effects of fish oil and aspirin on platelet aggregation were investigated using single and dual agonists. Although fish oil alone did not significantly raise aggregation thresholds for collagen, arachidonic acid, or PAF, it did reduce the extent of aggregation with collagen. When challenged by single or dual agonists, the combination of fish oil and aspirin did not make platelets less sensitive than did aspirin alone. Since fish oil and aspirin had synergistic effects on bleeding times, but not on platelet aggregation, these two substances appear to affect hemostasis by different mechanisms. PMID- 2109372 TI - FVIII concentrates: old and new. PMID- 2109373 TI - [Detection of infectious hemorrhagic disease of domestic rabbits (rabbit viral hemorrhagic disease) in wild rabbits (Oryctolagus cuniculus)]. AB - The occurrence of Rabbit Viral Hemorrhagic Disease of domestic rabbits in the population of wild rabbits in Germany was proven through detection of antigen (hemagglutination) in spleen and liver in one animal and through detection of specific antibody in another animal. There was no epizootic connection between the two animals (different locations). The necropsy and histopathologic findings are presented from five wild rabbits which died from RVHD. PMID- 2109374 TI - [The therapeutic effect of a biogenic paste in experimental chronic periodontitis]. AB - The efficacy of a biogenic paste containing calcium phosphate and chondroitin sulfate was studied in dogs with experimental chronic periodontitis. The paste exerted a therapeutic effect on the periapical inflammatory destructive foci, relieving the inflammation and stimulating the reparative processes in the bone. PMID- 2109375 TI - Hemorrhagic transformation following tissue plasminogen activator in experimental cerebral infarction. AB - The effect of an intravenous infusion of recombinant tissue plasminogen activator on hemorrhagic transformation early after middle cerebral artery territory ischemia was studied in an established awake nonhuman primate (baboon) model. Following 3 hours' occlusion of the middle cerebral artery and 30 minutes' reperfusion in each of 30 baboons, a 60-minute infusion of recombinant tissue plasminogen activator (at three doses: Group A, 0.3 mg/kg, n = 6; Group B, 1.5 mg/kg, n = 6; Group C, 10 mg/kg, n = 6) or normal saline (n = 12) was undertaken. The frequency and volume of intracerebral hemorrhage, the volume of infarction, and clinical alterations were determined by computed tomography at 24 hours and 10 days, neuropathology at 14 days, and serial daily neurologic evaluations, respectively. Peripheral (nonintracranial) hemorrhage (Group A, p = 0.46; Group B, p = 0.015; Group C, p = 0.002) and peak plasma tissue plasminogen activator levels varied directly with the dose of recombinant tissue plasminogen activator. Petechial hemorrhagic infarction was a common finding among the 30 baboons. No significant differences in the incidences or volumes of infarction-related hemorrhage were apparent in any group compared with the respective saline-treated baboons. In pooled data, no significant relation between the volume of hemorrhage and the volume of infarction could be established. We conclude that the incidence and severity of hemorrhagic transformation are not related to infarction size and that recombinant tissue plasminogen activator does not increase the incidence or severity (volume) of hemorrhage when given early (less than or equal to 3.5 hours) after the onset of focal cerebral ischemia in this model. PMID- 2109376 TI - Delayed treatment with a t-PA analogue and streptokinase in a rabbit embolic stroke model. AB - Fibrinolytic therapy may be effective in the treatment of ischemic stroke, and clinical trials are under way. We evaluated two fibrinolytic agents, an analogue of tissue plasminogen activator (Fb-Fb-CF, the catalytic fragment of the tissue plasminogen activator molecule with a prolonged serum half-life, n = 10) and streptokinase (n = 7), in a rabbit model of embolic stroke. Both agents were given 3 hours after stroke onset, a time relevant to the clinical setting. Fb-Fb CF was significantly better (p less than 0.04) than saline (n = 7) in restoring blood flow to previously occluded intracranial arteries, but streptokinase was ineffective. Neither fibrinolytic agent was associated with a substantial risk for intracerebral hemorrhagic side effects. Our study demonstrates that Fb-Fb-CF can safely and effectively reperfuse rabbit intracranial arteries 3 hours after occlusion, while streptokinase does not. PMID- 2109377 TI - Prolonged function of canine pancreatic fragments autotransplanted to the spleen by venous reflux. AB - The long-term viability and function of pancreatic islets transplanted as nonvascularized dispersed grafts has not been well established. We report maintenance of nondiabetic carbohydrate metabolism for up to 36 months (17.8 +/- 1.4 months) in 77% of 40 consecutive canine recipients of nonpurified islet grafts transplanted to the spleen by venous reflux. Spontaneous loss of graft function occurred in 9 dogs during the follow-up period. Failure usually occurred within 1 year of implantation and was predicted by low K value and low insulin output on intravenous glucose tolerance tests 1 and 3 months postimplant. High K values and insulin output correlated strongly with maintenance of function beyond 24 months. A sufficient mass of implanted islets can provide satisfactory metabolic control for prolonged periods. PMID- 2109378 TI - DNA replication in mouse pancreatic islets transplanted subcapsularly into the kidney or intraportally into the liver. Influence of unilateral nephrectomy or partial hepatectomy. AB - 3H-thymidine incorporation into DNA (estimated as the autoradiographic labeling index [LI]) was used as an index of DNA replication in syngeneic mouse islets grafted into the kidney or liver 4 weeks before unilateral nephrectomy (UN) or partial hepatectomy (PH). Removal of one kidney resulted in a significantly increased growth of the remaining islet-bearing kidney initiated during the first week after surgery. Seven days after 40% hepatectomy the remaining liver mass corresponded to 91% of that of sham-operated (SO) mice. The induced kidney and liver growth in mice subjected to UN or PH was correlated with an increased LI, which was similar in both organs (3.5 times the LI in kidneys and livers of SO controls). Pancreatic islets implanted into the organs undergoing compensatory growth also had higher LI values that were less pronounced as compared with the LI measured in the parenchymal cells of the kidney or the liver after UN or PH, respectively. In contrast to the grafted islets, no changes in the LI of the endogenous pancreatic islets were found. To evaluate possible systemic effects of the induced growth stimulation, the livers of UN-mice and the kidneys of PH-mice were investigated. No change in the LI of the liver tissue was observed 3 and 6 days after UN, whereas the kidney cortex showed a significantly increased LI7 days after PH. It is concluded that when exposed to a local, non-specific growth stimulation in vivo pancreatic islets prepared from adult donors are able to respond with an enhanced replicatory activity. The effect is, however, only present when the islets are located in the organs in which growth has been induced. PMID- 2109379 TI - In vivo cell activation following OKT3 administration. Systemic cytokine release and modulation by corticosteroids. AB - A massive and self-limited release of tumor necrosis factor and interferon gamma was detected in the systemic circulation in 35 consecutive renal allograft recipients by specific radioimmunoassays very soon following the first injection of the monoclonal antibody OKT3 (anti-CD3). Peak serum TNF and IFN gamma levels were reached, respectively, at 1 and 4 hr following the first OKT3 injection. Abnormally high serum interleukin 2 levels were also observed 4 hr following the first OKT3 injection in a minority of patients (5 cases). OKT3 had no effect on interleukin 1 beta, interferon alpha, and granulocyte/macrophage colony stimulating factor serum levels, which in all patients remained within the normal range throughout the study. This selective OKT3-induced cytokine release, which only followed the first injection, was transient (i.e., lasting a few hours). It tightly paralleled the spontaneously reversible clinical syndrome characterized by high fever, headaches, and gastrointestinal symptoms that is invariably associated with the first OKT3 administration. Importantly, when administered in adequate dosages and with adequate timing, corticosteroids influenced both the cytokine release and the systemic reaction. Thus, the highest TNF, IFN gamma, and IL-2 serum levels were detected in patients who did not receive corticosteroids. Patients who received high-dose corticosteroids (1 g solumedrol bolus) concomitantly with the first OKT3 injection still had high TNF and IFN gamma levels. Conversely, when the same corticosteroid dose was injected 15-60 min prior to the first OKT3 injection, in all cases the increase of serum TNF and IFN gamma was significantly lower as compared with the above-described groups; IL-2 levels did not rise. These data offer a direct explanation for one major side effect of OKT3 and thus provide the basis for devising means to prevent its occurrence. PMID- 2109380 TI - The effect of prostacyclin as a constituent of a preservation solution in protecting lungs from ischemic injury because of its vasodilatory properties. PMID- 2109381 TI - Donor pretreatment with lidocaine decreases incidence of early renal dysfunction in cadaver kidney transplantation. PMID- 2109382 TI - Thyroid hormones and their impact on the hemodynamic and metabolic stability of organ donors and on kidney graft function after transplantation. PMID- 2109383 TI - Should cadaveric donors with positive serology for Chagas' disease be excluded for kidney transplantation? PMID- 2109384 TI - Preservation of the liver with the HTK solution. PMID- 2109385 TI - Ischemia-reperfusion injury in an ischemic rat liver model: relationship between oxygen-derived free radicals and prostaglandins. PMID- 2109386 TI - Pancreas preservation prior to islet isolation: evaluation of storage solutions in a rodent model. PMID- 2109388 TI - Second International Congress on Pancreatic and Islet Cell Transplantation. Minneapolis, Minnesota, September 21-22, 1989. PMID- 2109387 TI - Reversal of diabetes by transplantation of pure cryopreserved canine islets. PMID- 2109389 TI - Safety and patient satisfaction with outpatient-administered OKT3 in combined kidney/pancreaticoduodenal allograft recipients. PMID- 2109390 TI - Endocrine function of the pancreas after transplantation: the contribution of partial pancreatectomy, systemic hormone delivery, and duct obliteration to glucose regulation by the canine pancreas. PMID- 2109391 TI - Tissue reaction to implanted bioartificial pancreas in pigs. PMID- 2109392 TI - Glucagon response to hypoglycemia and the effect of oral glucose tolerance test on gastric inhibitory polypeptide secretion in pancreas transplanted pigs. PMID- 2109393 TI - Cyclosporine treatment of BB rat pancreas transplant recipients: a functional and histologic analysis. PMID- 2109394 TI - Limited survival of human preislet cells transplanted into diabetic renal transplant recipients after 15 months. PMID- 2109395 TI - The role of retinoic acid in maturing the insulinogenic response of the human fetal pancreas to glucose. PMID- 2109396 TI - Islet isolation from human pancreas stored in UW solution for 6 to 26 hours. AB - 1. Viable and functional islets can be recovered from human pancreata stored for prolonged periods (up to 18 hours) with either the UW solution or EC. 2. Function of islets from pancreas stored in UW solution appeared superior. However, the difference in these preliminary studies does not appear nearly so dramatic as in transplantation of vascularized pancreas. 3. Function of islets from human pancreas stored for longer than 18 hours after UW in situ flush was uniformly poor. 4. Considerable room for improvement in the storage of human pancreas before isolation exists. Progress in this area will be important for the development of any large-scale program of clinical islet transplantation. PMID- 2109397 TI - Alteration in diabetic retinopathy and nephropathy following islet transplantation. PMID- 2109398 TI - Intrahepatic islet autografts in dogs function despite completely diverting portacaval shunt. PMID- 2109399 TI - Canine islet autografts: functional outcome as influenced by islet number and purity. PMID- 2109400 TI - The blood perfusion of autotransplanted pancreatic islets in the rat. PMID- 2109401 TI - Islet purification by a novel immunomicrosphere cell depletion technique. PMID- 2109402 TI - Treatment of primate islets with anti-class II antibodies and complement fails to deplete class II-bearing cells. PMID- 2109403 TI - Experimental perfusion model of autotransplanted islets in canine spleen. PMID- 2109404 TI - The microvasculature of xenogeneic transplanted islets of Langerhans. PMID- 2109405 TI - Effect of diabetes on the function of transplanted human islets of Langerhans. PMID- 2109406 TI - Development of human fetal xenograft transplants in diabetic nude mice. PMID- 2109407 TI - Primary nonfunction of pancreatic islet allografts in different rat strains. PMID- 2109408 TI - Characterization of mononuclear infiltrates in rejecting and surviving murine islet allografts. PMID- 2109409 TI - The effect of early islet transplantation on prevention of nephropathy in the spontaneously diabetic BB rat. PMID- 2109410 TI - Functional maturation of fetal porcine isletlike cell clusters after transplantation into nude mice. PMID- 2109411 TI - Histocompatibility of semipermeable membranes for implantable diffusion devices (bioartificial pancreas). PMID- 2109412 TI - Effect of third-party, MHC-incompatible allograft rejection on cultured islet allografts. PMID- 2109413 TI - Effect of isolated and purified splenic dendritic cells (antigen presenting cells) on initiation of islet allograft rejection. PMID- 2109414 TI - The importance of donor MHC compatibility in the allo- and autoimmune destruction of islet grafts in the BB rat. PMID- 2109415 TI - Successful transplantation of neonatal rat islets is dependent upon both method of isolation and histocompatibility barrier. PMID- 2109416 TI - Islet endocrine cell MHC antigen expression in allograft rejection. PMID- 2109417 TI - Immunologic consequences of islet MHC antigen modulation in autoimmune diabetes. PMID- 2109418 TI - Studies of host immunomodulation and prevention of pancreatic beta cell destruction. PMID- 2109419 TI - Expression of class II antigen on neonatal rat islets by interferon and tumor necrosis factor: lack of correlation of expression of class II antigen and allograft rejection. PMID- 2109420 TI - Destruction of islet isografts by severe nonspecific inflammation. PMID- 2109421 TI - Effect of host immunomodulation on the prevention of islet allograft primary nonfunction in a murine model. PMID- 2109422 TI - Protein coat causes improved insulin diffusion through membranes for immuno isolated islet transplantation: improved islet survival by pretreatment of membranes and islets. PMID- 2109423 TI - Transplantation of islets of Langerhans in millipore diffusion chambers. PMID- 2109424 TI - Fish oil diet prevents insulitis in transplanted islets of Langerhans. PMID- 2109425 TI - Islet transplantation in outbred rats using cyclosporine. PMID- 2109426 TI - RS-61443 allows islet allografting and specific tolerance induction in adult mice. PMID- 2109427 TI - Prolongation of islet isograft survival in diabetic NOD mice by anti-L3T4 and anti-LYT2 monoclonal antibodies. PMID- 2109428 TI - The effects of thiamin on the neurophysiological alterations induced by lead. AB - The neurophysiological and histopathological alterations were evaluated in Sprague-Dawley rats exposed to 1,000 ppm lead in drinking water and treated with thiamin (25 mg/kg or 50 mg/kg bw), calcium ethylenediamine tetraacetic acid (CaEDTA) (50 mg/kg bw) or their combination for 8 weeks. Alterations in the brain stem auditory evoked responses (BAERs) were observed during the treatment period. Latency periods associated with the BAERs were increased after 4 weeks of lead exposure. The neurophysiological alterations induced by lead exposure were prevented by thiamin or CaEDTA treatment. The latency periods in the lead exposed rats treated with thiamin, CaEDTA or the combined treatment did not increase in a similar fashion, but resembled more closely the latency periods observed in the rats which were not exposed to lead. The higher dose of thiamin (50 mg/kg) was more effective than the lower dose (25 mg/kg) in the comparable treatment groups. Histopathological examination of the animals did not reveal any pathological changes in the brain, although lesions often associated with lead toxicity were observed in the kidney. The severity of the lesions was not influenced by thiamin or CaEDta treatment. The absence of morphological damage in the CNS in the presence of neurophysiological alterations, indicates that functional deficits may be observed prior to histological evidence of pathological damage. PMID- 2109429 TI - Symptomatic nitroglycerin toxicity from erroneous use of topical nitroglycerine. PMID- 2109430 TI - The disposition of tert-butyl-D-serine in the rat. AB - 1. Following intravenous administration of 14C-tert-butyl-D-serine to rats, radioactivity was eliminated rapidly via the kidneys. 2. One metabolite was detected in urine and was identified as the N-acetyl derivative of tert-butyl serine. 3. Elimination was more rapid in female than male rats. PMID- 2109431 TI - The metabolism of nafimidone hydrochloride in the dog, primates and man. AB - 1. The biotransformation of nafimidone, an imidazole-substituted anticonvulsant, has been studied by characterization of urinary metabolites in dogs, cynomolgus monkeys, baboons and man. 2. The biotransformation of nafimidone in these laboratory animals and man is initially very similar, in each case proceeding by reduction to the aliphatic alcohol metabolite, nafimidone alcohol or 1-[2-hydroxy 2-(2-naphthyl)ethyl]imidazole. 3. Further transformation of this metabolite involves oxidation in the naphthyl and imidazole functions, and/or conjugation. 4. The dog differs from the higher primates in that no metabolic modification of the naphthyl group takes place, the major metabolite in the dog being the O-beta glucuronide of nafimidone alcohol. 5. In higher primates and man two isomers involving dihydroxylation in the naphthyl ring--1-[2-hydroxy-2-(5,6- or 7,8 dihydroxydihydro-2-naphthyl)ethyl]imidazole--were tentatively identified. These species alone showed evidence of an imidazole linked N-glucuronide of nafimidone alcohol. 6. The possible occurrence of stereoselective metabolism by the introduction of a chiral centre at C-9 in nafimidone alcohol was indicated in human urine by the presence of both epimers of the O-beta-glucuronide of nafimidone alcohol in a 2:1 ratio. PMID- 2109432 TI - A double-blind, placebo-controlled study of the efficacy of Lactinex in the prophylaxis of amoxicillin-induced diarrhea. AB - The disruption of the natural flora of the gastrointestinal tract (especially Lactobacillus acidophilus) may occur during antibiotic therapy. This may lead to diarrhea, dehydration, and electrolyte imbalances. It has been suggested that replacement of the lactobacilli with a commercially available product may prevent the diarrhea. The efficacy and safety of prophylactically administered Lactinex (culture of L. acidophilus and L. bulgaricus) was compared with placebo for the prevention of amoxicillin-induced diarrhea in pediatric patients. Lactinex or placebo was administered four times a day for ten days to coincide with the antibiotic therapy. The Lactobacillus preparation did not appear to consistently prevent diarrhea in this patient population. Patients' age, diet, and parental definition of diarrhea were factors that may have influenced the results. PMID- 2109433 TI - Impact of college of pharmacy-based educational services within the hospital. AB - Using a pharmacy intervention form, we measured the influence that university based pharmacy educational personnel had on the pharmacy department's drug costs and on patient charges over a three-month period. A total of 278 interventions were made; 88.8 percent were implemented. Implemented interventions decreased drug costs by $1661.99 and decreased patient charges by $5938.37. The average implemented intervention decreased drug cost by $6.73 and patient cost by $24.04. Regardless of economic benefits, 218 of the 247 implemented interventions were considered to have positive clinical effects on patient care. Educational personnel were responsible for generating $6028.27 of fee revenues to the pharmacy department through generation of pharmacokinetic drug dosing consults. We conclude that the educational programs provided by the pharmacy department through affiliation with a college of pharmacy directly contributed $7690.26 to the pharmacy department in the form of cost-avoided dollars and revenue generation over a three-month period. The provision of educational services by a hospital pharmacy department results in financial rewards as well as other benefits that have been previously described. PMID- 2109434 TI - [The antimicrobial effect of selected disinfectants in combination with anionic active detergents]. AB - The bactericidal activity of chloramine and hydrogen peroxide can be increased with only few exceptions through admixture of various anionic detergents in dependence of the concentration of the detergent (used concentrations between 0.008-5.3%). On the other hand at chloride of lime only in a few cases was possible to indicate advantageous effects of combination. PMID- 2109435 TI - [Survival of microorganisms on surfaces in relation to moisture and temperature and the effect of desiccation of microorganisms on resistance to disinfectants]. AB - In laboratory tests with carriers (glass, slab, blanket) at a high rel. humidity (95%) the survival was distinctly reduced by S. aureus at 37 degrees C and by Ps. aeruginosa at 21 degrees C and 37 degrees C. Against this after 24 h storing of contaminated carriers (glass) the resistance to disinfectants was higher at 95% rel. humidity as at 35% rel. humidity. PMID- 2109436 TI - [Status of diabetes in Ethiopia as a contribution to tropical diabetes mellitus]. AB - On the basis of own experiences with the care of diabetes in the northern highland of Ethiopia the particularities of the tropical diabetes mellitus are described. In the light of the control score according to Noviks and co-workers the quality of the metabolic management of 100 patients is estimated as above all unsatisfactory, from which the conclusion is to be deduced more than up to now to include the diabetes mellitus into the health care system of Ethiopia and to improve thoroughly the conditions for the diagnostics, the therapy, education and dispensary care. PMID- 2109437 TI - [An intracutaneous test with gonococcal allergen in married couples with impaired reproductive function]. AB - Comparative study of the diagnostic value of intracutaneous test with Gonococcus allergen, bacterioscopic and bacteriologic methods used in examinations of 200 married couples suffering from infertility have demonstrated a high sensitivity of the intracutaneous test. This test is recommended for wide use in screenings for gonorrhea in examinations of patients with impaired reproductive function. PMID- 2109438 TI - Correlation of clinical and serological findings in patients with rheumatoid arthritis treated for one year with interferon-gamma. AB - Results of a large therapeutic trial of interferon-gamma in patients with rheumatoid arthritis (RA) are described. Of 110 RA-patients enrolled in this clinical trial, 46 were treated with interferon-gamma for 12 months. During the treatment period, dosage was reduced on an individual basis. There was a correlation between the improvement of clinical parameters, such as pain or morning stiffness, and the improvement of laboratory parameters such as erythrocyte sedimentation rate, anemia, leucocytosis or thrombocytosis. Interferon-gamma was well tolerated, and no organ toxicity was detected. PMID- 2109439 TI - [Pathomorphology of mucopolysaccharidoses]. AB - Mucopolysaccharidoses are autosomal recessive or X-linked hereditary lysosomal storage diseases occurring to one in 10,000 to 16,000 births. The definitive diagnosis is based on the biochemical verification of the enzyme defect in cultured fibroblasts of amniotic fluid cells, in amniotic fluid, in chorionic biopsies and by determination of the urinary excretion of glycosaminoglycans. Morphological studies are of utmost importance both for genetic counselling and enlightenment of the pathogenesis. In recent years, numerous reports appeared dealing with morphological changes in different types of mucopolysaccharidoses. Based on own studies in pre- and postnatal cases, the present paper gives an update review on light and electron microscopic peculiarities of the different types and subtypes of mucopolysaccharidoses according to the classification of MCKUSICK and NEUFELD (1983). Lysosomal storage is found in practically all organs. However, there are quantitative and qualitative differences which are responsible for variations in clinical symptomatology. The purpose of this paper is to describe these differences with particular emphasis on changes in various tissues, on the pathogenetic mechanism of the storage as well as on pre- and postnatal morphological diagnostics. PMID- 2109440 TI - [CNS involvement in neurofibromatosis. A postmortem study]. AB - Neurofibromatosis was recorded from 30 in 82,249 postmortem cases (0.036%) at the Medical Academy of Erfurt, Institute of Pathological Anatomy, between June 1, 1945 and December 31, 1986, among them 13 cases of classical peripheral neurofibromatosis generalisata Recklinghausen (NgR) and 17 with CNS involvement. These had been 10 males and 7 females who had died at an age from 8 to 77 years (average age and death being 39 years). CNS lesions were preferentially localised in periventricular sections of the third and fourth ventricles and the cerebral aquaeduct, with diffuse gliosis being recorded from 5 cases. Typical bilateral neurofibromatosis of the acoustic nerve was established from three males aged 19, 26 and 30 years. Spinal neurinoma or neurofibroma, meningioma, an astrocytoma of the cervical spinal cord, and leptomeningeal sarcomatosis were also recorded. Additional skeletal abnormalities were exhibited by four cases. Interest is generally growing in CNS involvement in neurofibromatosis due to the possibility of intravital diagnosis by computed tomography (CT) and magnetic resonance spectroscopy (MRI) and because of possible surgical therapy. Recent studies in molecular genetics, on the other hand, have shown classical NgR to be caused by a lesion to chromosome 17, while bilateral neurofibromatosis of the acoustic nerve was found to be based on a genetic defect to the long arm of chromosome 22. PMID- 2109441 TI - [Allogenic transplantation of bone marrow in hematologic diseases. Preparation and completion of transplantation at the Hematology Clinic in Novi Sad]. AB - The paper deals with the results of clinical preparations for the application of allogenic bone marrow transplantation at the Clinic of Hematology in Novi Sad. The obligation of the definite treatment of patients below 45 years by allogenic and autologous bone marrow transplantation results from the acceptance of the Yugoslav protocols for acute leukaemia treatment. Thus immunogenotypical analyses, so far performed in patients with severe aplastic anaemia have been extended to patients with acute leukaemia as well and then to patients with chronic myelogenous leukaemia, high risk lymphocYtic lymphoma and myeloma multiplex with resistance to standard chemotherapy and their potential sibling donors. The bone marrow transplantation Unit has been set up, the team of specialists has been formed and educated and the protocol for allogenic transplantation with Busulfan and cyclophosphamide combination for pretransplant conditioning has been adopted. In research work concerning the field of bone marrow transplantation a particular emphasis has been put on the working out of a mathematical model for optimal timing of bone marrow transplantation in patients with acute myelogenous leukaemia. PMID- 2109442 TI - Ageing does not influence the ultrashort feedback control of GnRH secretion in vitro. AB - Evidence indicates that long and short feedback systems are altered in the aged male rat. Data also indicate the existence of an ultrashort feedback mechanism controlling GnRH secretion. The present experiments were performed to test whether the ultrashort feedback control of GnRH is operating also in old male rats. Mediobasal hypothalami of 18-month-old male rats were perifused in vitro either in the presence or in the absence of a GnRH agonistic analogue (Buserelin: [D-Ser(TBU)6,Des-Gly10]GnRH ethylamide) and stimulated with 5-min pulses of K+ (for a total of six pulses) in order to test their ability to release GnRH. The hypothalamic fragment was exposed to the GnRH analogue either for a part of the experimental period (at the beginning or at the end) or for the whole duration of the perifusion. In both cases, the presence of the analogue diminished or totally abolished the responses to K+ stimulation. This is in line with the results obtained in young animals. The data suggest that the ultrashort feedback mechanism controlling GnRH release is normally functioning also in aged male rats despite the fact that other types of feedback mechanisms (long and short loop) are substantially altered. PMID- 2109443 TI - The effect of orchidectomy on rat pituitary responsiveness to GHRH depends on age. AB - Pituitary responsiveness to GHRH (1-29) NH2 (GHRH, 5 micrograms/kg iv) was analysed under sodium pentobarbital anesthesia (50 mg/kg ip), on days 30 and 90 in male rats orchidectomized or sham-operated 7 days earlier. Other groups of rats were orchidectomized or sham-operated on day 23 and tested on days 30, 45, 60 and 90. In the sham-operated animals, GHRH stimulated GH secretion on day 90, but not on day 30. GHRH-induced secretion was similar on days 45, 60 and 90 in orchidectomized and sham-operated animals. Orchidectomy on day 83 reduced this GHRH-induced GH secretion on day 90. In contrast, orchidectomy on day 23 enhanced the pituitary responsiveness to GHRH a week later. These results suggest that the increase in pituitary responsiveness to GHRH with age is independent of the testicular function and that the effect of orchidectomy depends on both the age of the rats at orchidectomy and the time elapsed between the orchidectomy and the administration of GHRH. PMID- 2109444 TI - Histamine-induced paradoxical GH response to TRH/GnRH in men and women: dependence on gonadal steroid hormones. AB - A stimulatory GH response to TRH and GnRH occurs frequently in patients with various pathological conditions, but is absent in normal subjects. We have previously shown that histamine induced a paradoxical GH response to TRH in normal men. Since gonadal steroids influence GH secretion, we investigated whether infusion of histamine might induce a GH response to combined administration of TRH (200 micrograms) and GnRH (100 micrograms) in 6 normal women during the early follicular and luteal phase of the same menstrual cycle and in 7 normal men. Histamine had no effect on basal GH secretion in men or in women during the two phases of the menstrual cycle. However, compared with saline, histamine induced a GH response to TRH/GnRH in men (GH peak: 5.5 +/- 1.0 vs 1.4 +/- 0.3 micrograms/l; p less than 0.01) and in women during the luteal phase (GH peak: 5.2 +/- 1.6 vs 1.5 +/- 0.4 micrograms/l; p less than 0.025), but not during the early follicular phase of the cycle (GH peak: 1.7 +/- 0.5 vs 1.6 +/- 0.3 micrograms/l). In luteal-phase women the GH response to TRH/GnRH correlated with the serum estradiol-17 beta level (GH area/E2: r = 0.98; p less than 0.005) and the serum estrone level (GH area/E1: r = 0.81; p less than 0.05). In men the GH response to TRH/GnRH did not correlate with estrogen or androgen levels. We conclude that high physiological levels of estrogens are pertinent to the activation of a histamine-induced GH response to TRH/GnRH in women, whereas the role of androgens and estrogens for the induction of the response in men seems more complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109445 TI - Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects. AB - Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1-29) NH2 100 micrograms iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 +/- 4 vs 44 +/- 16 micrograms/l; mean +/- SEM). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 +/- 5 vs 77 +/- 20 micrograms/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli. PMID- 2109446 TI - Thyroid sonography in autoimmune thyroiditis. A prospective study on 123 patients. AB - Thyroid sonography was used to assess 2322 patients attending our clinic over a 3 year period. Sonography, in combination with clinical and laboratory findings, enabled us to detect autoimmune thyroiditis in 123 patients, 67 of whom could be classified as euthyroid, 17 as latent hypothyroid, and 39 as overtly hypothyroid. Consequently without the use of sonography (or thyroid antibody measurements) it would not have been possible to make a diagnosis in over half of our patients with autoimmune thyroiditis. Sonography was also of considerable value in establishing the absence of autoimmune thyroiditis as out of the 2322 patients we examined, autoimmune thyroiditis could be excluded on the basis of sonography alone (absence of diffuse hypoechoicity) in 1962 (84%). Thyroid volume ranged from less than 5 to 112 ml with the majority of patients having a volume of 21-30 ml and the overtly hypothyroid group showing a shift to smaller volumes. The data suggested that thyroid volume changes over the range of the disease from euthyroid to overtly hypothyroid. PMID- 2109447 TI - HLA antigens and haplotypes associated with idiopathic haemochromatosis in Veneto: peculiar association with HLA-A3,B35. AB - HLA-A and HLA-B antigens were determined in 16 unrelated subjects orginating from Veneto affected by idiopathic haemochromatosis (IH). HLA-A3 was found in 13/16 patients vs. 300/1,348 controls (p less than 0.00005). Prevalences of A3,B35 haplotype were 0.4375 in patients vs. 0.0816 in controls (p less than 0.0005). Linkage disequilibrium analysis proved the existence of a positive third-order linkage disequilibrium among IH, HLA-A3 and HLA-B35 alleles. Our data confirm the close association of IH and HLA-A3 and prove the peculiar association of the disease with A3,B35 haplotype in north-eastern regions of Italy. The positive third-order linkage disequilibrium suggests a remote event (mutation, recombination or immigration) as origin for IH and A3,B35 association. PMID- 2109448 TI - Continuous infusion chemotherapy with epirubicin and vincristine in relapsed and refractory acute leukemia. AB - Twenty-three patients admitted for treatment of refractory or relapsed acute leukemias (12 acute nonlymphocytic leukemias, 4 acute lymphocytic leukemias, 1 acute undifferentiated leukemia, 6 chronic myeloid leukemias in blast crisis) received a regimen employing a 4-day continuous intravenous infusion of epirubicin followed by a 4-day continuous infusion of vincristine. The remission rate (complete and partial) was 52%. This treatment was associated with minimal extrahematologic toxicity, particularly cardiac and gastrointestinal toxicity. This method of administration should be considered a reasonable therapeutic approach to pretreated acute leukemia patients, particularly in elderly patients wishing to avoid chemotherapy-related side effects. PMID- 2109449 TI - High incidence of cholelithiasis in older patients with homozygous beta thalassemia. AB - The records of 48 patients with homozygous beta-thalassemia were reviewed for evidence of cholelithiasis by abdominal ultrasonography or plain abdominal X-ray. The presence of cholelithiasis was reported in 25 patients (52%). The incidence increased with age to 83% in patients over 31 years of age. Gallstones were more frequent among patients with beta-thalassemia intermedia and with less blood transfusion requirements. Eleven patients with cholelithiasis (44%) became symptomatic. Eight received operations on an elective or semielective basis. Another patient had incidental cholecystectomy during splenectomy. The preoperative evaluation included abdominal ultrasonography, nucleotide biliary scan and evaluation of the cardiopulmonary status. Due to the longer survival of patients with homozygous beta-thalassemia, the problem of cholelithiasis is becoming more frequent. PMID- 2109450 TI - Immunophenotypic analysis of lymphocytes and myeloma cells in patients with multiple myeloma. AB - The immunological phenotypes of lymphocytes and myeloma cells in 48 patients with multiple myeloma (MM) were analyzed using a panel of monoclonal antibodies (mAbs). Myeloma cells were positive for OKT10, BL3, PCA1 and BA2. In a few cases, they were also positive for the B cell-associated antigens J5, B1 and I2. Eight of 48 cases had more than 15% J5-positive lymphocytes, and some lymphocytes in MM expressed plasma cell-associated antigens (PCA1, BL3, OKT10), suggesting a possible clonal involvement. These observations demonstrate the heterogeneity of surface antigen expression of myeloma cells and suggest that BL3, PCA1, BA2 and J5 may be useful mAbs for purging myeloma cells from bone marrow for autologous transplantation. PMID- 2109451 TI - Selenium and glutathione peroxidase levels in sickle cell anemia. AB - Levels of plasma selenium (Se) and glutathione peroxidase were measured in 20 sickle cell anemia (SCA) patients not in crisis and in 14 nonanemic control subjects. The results show that the levels of Se and glutathione peroxidase were significantly (p less than 0.005) lower than those of controls in both plasma and whole blood. These data are consistent with the previous reports that there is increased oxidative stress in SCA. Low blood Se levels and glutathione peroxidase activity observed in this research suggest that a weakened antioxidant potential may be associated with SCA patients. The low Se status in SCA patients may also affect the phenotypic expression of these patients. PMID- 2109452 TI - Autocrine growth by two cytokines, interleukin-6 and tumor necrosis factor alpha, in the myeloma cell line KHM-1A. AB - The effects of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) on the cell growth of the myeloma cell line KHM-1A were studied. TNF-alpha strongly induced KHM-1A proliferation, while IL-6 weakly enhanced growth only at low cell densities. When TNF-alpha was combined with IL-6, TNF-alpha-induced growth enhancement was reduced. According to Northern blotting analysis, the m RNA of both TNF-alpha and IL-6 were detected in KHM-1A. Moreover, monoclonal antibody capable of neutralizing the cytotoxic activity of TNF-alpha inhibited the proliferation of this cell line. These findings suggest that this cell line operates under an autocrine growth mechanism with respect to these two cytokines, IL-6 and TNF-alpha. PMID- 2109453 TI - Iron overload in untransfused patients with hemoglobin H disease. AB - Two Chinese patients with hemoglobin (Hb) H disease without a history of blood transfusion developed iron overload at the age of 45 and 53 years, respectively. Human leukocyte antigen (HLA) system types of these 2 patients were A19, A11, B13, B62 and A2, A24, BW55, respectively, which are not related to the common haplotypes for idiopathic hemochromatosis. Since severe iron loading is a rare clinical manifestation in untransfused patients with Hb H disease, the iron overload in both patients may be due to environmental or underlying genetic factors. PMID- 2109454 TI - Evidence for the neoplastic involvement of monocytic, eosinophilic and basophilic lineages in acute myelomonocytic leukemia with eosinophilia. AB - To investigate the origin of cells observed in acute myelomonocytic leukemia with eosinophilia (M4E0), we carried out morphological and cytogenetic studies of colonies derived from leukemic precursors. Marrow cells from a patient with M4E0 at second relapse revealed an abnormal karyotype; 47,XY, +8, inv(16)(p13q22), 17p . Cytogenetic studies of leukemic colonies showed the same karyotypic abnormality. The primary and secondary colonies consisted of monocytes, eosinophils and basophils. These results indicated that the neoplastic process in this patient originated in a stem cell capable of differentiation into at least monocytes, eosinophils and basophils. PMID- 2109455 TI - Alpha interferon dose-dependent suppression of secondary clones in a patient with Philadelphia-positive chronic myelogenous leukemia. AB - A patient whose chronic myelogenous leukemia (CML) was treated with interferon alpha (IFN-alpha) is described. The disease showed karyotypic evolution during the chronic phase and the later myeloid acceleration. Both of these secondary clonal phenomena responded to IFN-alpha dose escalation. The case illustrates the dose dependence of CML responses to IFN-alpha. The phenomenon of clonal evolution is discussed in the context of this patient's disease. PMID- 2109456 TI - Asymptomatic homozygous protein C deficiency. AB - We report a family in which 2 homozygotes with similarly very low protein C levels have different clinical symptoms. One had recurrent venous thrombosis starting at the age of 28 years, the other is still asymptomatic at 38 years despite exposure to thrombotic risk factors. Our review of 13 additional cases reveals a highly variable phenotypic expression of homozygous protein C deficiency, which can be subdivided into two groups. In the first group are 8 kindreds in which homozygotes presented at birth with unmeasurable protein C levels and life-threatening thrombosis and 1 kindred in which homozygotes are characterized by very low levels of protein C but delayed onset (10 months of age) of thrombosis. In the second group are 4 kindreds characterized by very low, but measurable, protein C levels in homozygotes who survived beyond the neonatal period into adulthood with histories of moderately severe thrombosis. The present case demonstrates that protein C levels lower than 10% are compatible with a negative history for thrombosis, not only in the neonatal period but also during adulthood, and suggests that in some homozygotes other factors need to interact for full clinical penetrance of the defect. PMID- 2109457 TI - Chlorambucil lung toxicity. AB - A 67-year-old man, who had received intermittent courses of oral chlorambucil and prednisone as therapy for chronic lymphocytic leukaemia over a period of 3.5 years, developed fatal lung fibrosis. A case report and brief review of the current data on chlorambucil-induced lung disease are presented. PMID- 2109458 TI - Long arm deletion of chromosome 7 unrelated to original karyotype in recurrent t(8;21) acute myeloblastic leukemia. AB - We describe a chromosomal abnormality, 7q-, unrelated to the original karyotype in a patient with recurrent t(8;21) acute myeloblastic leukemia. The 7q-, del(7)(q22q34), was seen in otherwise karyotypically normal cells. Cyclophosphamide was administered for 5 months during the maintenance therapy. Our observations indicate that unrelated karyotypes, besides karyotypic evolution, may be implicated in tumor cell heterogeneity and may support the previous documentation of a possibly causal relationship between chemotherapy and development of 7q-. A larger study will be required to elucidate the biologic significance, if any, of the unrelated karyotypes. PMID- 2109459 TI - Disseminated intravascular coagulation and myocardial infarction in a haemophilia B patient during therapy with prothrombin complex concentrates. AB - A case of disseminated intravascular coagulation (DIC) and fatal myocardial infarction in a haemophilia B patient is described. DIC occurred after 4 days of therapy with unactivated prothrombin complex concentrates during the post operative period. Therapy with fresh frozen plasma, heparin and antithrombin III concentrates was started without efficacy; after autopsy myocardial infarction was evident. PMID- 2109460 TI - Serum sickness from iron-dextran administration. AB - Hypersensitivity vasculitis occurs in response to various exogenous agents. A case of a serum sickness syndrome with cutaneous vasculitis is described in a patient given an intravenous iron-dextran infusion. PMID- 2109461 TI - Midazolam and flumazenil--the agonist-antagonist concept for sedation and anaesthesia. Proceedings of an international symposium. Sardinia, April 1989. PMID- 2109462 TI - Midazolam and flumazenil: the agonist-antagonist concept for sedation and anaesthesia. PMID- 2109463 TI - The use of midazolam and flumazenil in diagnostic and short surgical procedures. AB - Benzodiazepines, used correctly, provide a relatively safe means of providing sedation in a variety of clinical situations and midazolam, which is shorter acting than other benzodiazepines (BZ), is the drug of choice in ambulatory patients. Flumazenil is a highly effective specific competitive BZ antagonist which provides a safe means of rapidly attenuating or terminating BZ sedation. Its mean half-life is 54 min, and in this contact the optimal dosage is 0.2 to 0.5 mg. Although it reverses sedation and amnesia, there is still a question about whether its efficacy in reversing the respiratory depressant effects of benzodiazepines is adequate. This remains an area of critical debate, as does resedation and also its administration to chronic benzodiazepine users. The use of flumazenil to reverse midazolam-induced sedation introduces, for the first time, the possibility of terminating sedation at a predetermined time. Were it to be adopted routinely, it has major implications for the improvement of patient management affecting all aspects of post-operative care. PMID- 2109464 TI - Midazolam and flumazenil in gastroenterology. AB - Flumazenil, a specific benzodiazepine antagonist, has been used to reverse sedation in a double-blind, controlled study of patients undergoing upper gastrointestinal (GI) endoscopy. Forty patients in each of two centres were given a standard dose of either flumazenil (n = 40) or placebo (n = 40) after gastroscopy under midazolam sedation. Assessments were made of degree of sedation, psychomotor ability and amnesia up to 24 h after endoscopy. In patients treated with flumazenil, sedation was effectively reversed within 5 min in 77.5% of cases compared to 27.5% of patients treated with placebo. The difference was both clinically and statistically significant at 5 and 30 min but not at 60 min after reversal. There was no evidence of resedation 18 to 24 h later. Times to complete Trieger dot-joining tests were significantly faster in the flumazenil group at 5, 30 and 60 min. Amnesia for the procedure was retained but did not occur for events after administration of flumazenil. The only adverse event was severe pain in the arm of one patient during the injection of flumazenil. Flumazenil rapidly and safely reverses midazolam-induced sedation while retaining amnesia for gastroscopy. PMID- 2109465 TI - The role of midazolam and flumazenil in urology. AB - The effects of midazolam (3-10 mg i.m.) and their reversal by flumazenil were studied in transurethral endoscopic procedures performed using topical analgesia. In one randomised study, patients (n = 84) received either no medication or flumazenil (0.5 mg i.v.) on completion of endoscopy. Recovery was assessed subjectively. Within 15 min, 83% of those receiving flumazenil were considered ready for discharge compared with only 24% of the control group (P less than 0.001). In a second randomised, double-blind, placebo-controlled trial of 44 patients, post-operative recovery was assessed using five objective psychomotor tests. Whereas the placebo group took up to 2 h to recover, those receiving flumazenil recovered fully or returned to near control values within 15 min. Sedoanalgesia--a technique combining adequate local anaesthesia with sedation (using midazolam)--has wide application in urology, and the introduction of flumazenil has major implications for the practice of day-case surgery. PMID- 2109466 TI - The use of midazolam and flumazenil in cardiovascular diagnostic and therapeutic procedures. AB - Sedation is sometimes required for cardiovascular diagnostic or therapeutic procedures. Midazolam may be proposed in these situations because of its duration of action and because of its moderate haemodynamic effects. However, the use of midazolam implies that the standards of safety required for all anaesthetic techniques have been applied. The changes in haemodynamic data induced by the administration of midazolam must be taken into account in interpretation of the catheterisation report. At the end of investigation, flumazenil can be administered safely to reverse residual sedative effects of midazolam but its use does not exempt from normal monitoring during the recovery period. PMID- 2109467 TI - Midazolam and flumazenil in ophthalmology. AB - Midazolam's pharmacodynamic properties are used in ophthalmology in several indications: 1. to relieve anxiety and unwanted reactions during radial keratotomy in ambulatory patients; 2. to provide sedation and amnesia during cataract surgery using local anaesthesia, in combination with low doses of phenoperidine; 3. to induce general anaesthesia, combined with fentanyl and vecuronium, for intraocular surgery in the elderly; and 4. to decrease intraocular pressure. Flumazenil is not in routine use but is usually administered to antagonise the deleterious effects of midazolam on upper airway resistances and the respiration system and may be used to reverse "paradoxical", i.e. anxiogenic reactions to benzodiazepines in the elderly. PMID- 2109468 TI - The use of midazolam and flumazenil in locoregional anaesthesia: an overview. AB - Midazolam is useful as an intravenous supplement to local anaesthesia techniques in producing sedation, amnesia and anxiolysis, and has about five times the sedative potency of diazepam. Considerable interpatient variability exists in dose requirements, especially in elderly patients. The combined effects of local anaesthetics and midazolam may contribute to enhanced haemodynamic effects and changes in the respiratory pattern, impairing ventilation and oxygenation. Flumazenil can be titrated in incremental doses to reverse the residual sedative effects of midazolam, without intrinsic haemodynamic or respiratory effects, but may not fully antagonise the decrease in chemoreceptor sensitivity nor the changes in breathing pattern induced by midazolam. Patients treated with epidural or spinal anaesthesia supplemented with midazolam should be monitored to avoid hypoxaemia risks even after the administration of flumazenil. PMID- 2109469 TI - Autonomic and hormonal responses after the use of midazolam and flumazenil. AB - Midazolam, like other benzodiazepine agonists, reduces the autonomic and hormonal responses to emotional or surgical stress. This can be seen as a reduction in catecholamine levels after benzodiazepine treatment. The endocrine response with a reduction in cortisol values is mediated by a decrease in ACTH. The adrenal glands are immediately responsive to exogenous ACTH administration as well as to spontaneous recovery from the benzodiazepine action. Flumazenil given alone does not affect the response to emotional stress, neither does it cause any cardiovascular changes. Following benzodiazepine treatment, flumazenil given in a titrated fashion reverses the inhibitory effects of the agonists. PMID- 2109470 TI - Safety of rapid administration of flumazenil in patients with ischaemic heart disease. AB - The purpose of this study was to determine if higher (36 micrograms.kg-1) doses of flumazenil (a new benzodiazepine (BZ) antagonist) produced an effect on haemodynamics. Twelve patients with class III-IV angina were entered into this double-blind randomised placebo-controlled study. BZ were withheld for 2 weeks prior to surgery. Patients were placed on an ambulatory monitor 18 h prior to surgery to record changes in heart rate rhythm and ST segment changes. The patients were given secobarbital 100-200 mg and morphine 0.12 mg.kg-1 90 min prior to surgery. Flumazenil or placebo was given in divided doses every 3 min (1 mg, 1 mg, 1 mg). Complete haemodynamic profiles were obtained at baseline and 2 min following each injection of flumazenil. Flumazenil produced a minimal but statistically significant reduction in systolic blood pressure (147 +/- 13.9 to 137 +/- 18.4 mmHg) and diastolic blood pressure (74 +/- 14.8 to 67 +/- 13 mmHg). There was no consistent effect on heart rate, pulmonary capillary wedge pressure or cardiac index. We conclude that flumazenil is safe when administered in relatively high doses to patients with ischaemic heart disease who have not received benzodiazepines. PMID- 2109471 TI - Speed of reversal of midazolam-induced respiratory depression by flumazenil--a study in patients undergoing upper G.I. endoscopy. AB - Intravenous midazolam was given to 17 patients coming to upper G.I. endoscopy. All patients had an ear oximeter and calibrated induction plethysmograph attached to record oxygen saturation and minute volume continuously. Midazolam induced significant depression of respiration. Following removal of the endoscope, a new base line was obtained before giving intravenous flumazenil in an attempt to reverse the sedative and ventilatory effects of midazolam. When 0.5 mg of flumazenil was given over 20 s, followed by 0.1 mg every minute, up to a total of 1.0 mg, all patients were apparently awake in under 2 min. Although the flumazenil had clearly reversed the sedative effects of midazolam, the ventilatory effects were largely uninfluenced. The implications are discussed. PMID- 2109472 TI - Pharmacology of Dormicum (midazolam) and Anexate (flumazenil). AB - Midazolam and flumazenil have some characteristics in common which make them suitable partners as benzodiazepine (BZD) agonist and antagonist. After intravenous (i.v.) administration, both drugs are rapidly distributed into similar distribution volumes, from which they are cleared with a comparable short elimination half-life (t1/2 beta) in the range of 1 h (flumazenil) to 3 h (midazolam). Both drugs undergo hepatic metabolisation with a relatively high hepatic extraction ratio of around 0.3 for midazolam and 0.6 for flumazenil. The metabolisation of midazolam and flumazenil may equally be affected by considerable loss of active liver cells or by temporarily reduced hepatic blood flow. In such a case, elimination of both drugs may be prolonged in the same way. Flumazenil has only an inactive metabolite. The main active alpha-hydroxy metabolite of midazolam does not contribute much to the activity of midazolam after parenteral administration. Its potency is lower than that of midazolam and its shorter elimination half-life (0.8 h) does not prolong the activity of the parent drug. As indicated by the therapeutic index, both drugs have a very high safety margin, which is considerably higher than that of thiopentone or propofol. Only low doses of both drugs are necessary to produce initial effects. Increasing doses intensify the drug activity and a ceiling effect is observed after maximal doses of midazolam and flumazenil. The onset of effect immediately follows the diffusion of the substances into the CNS and can be observed within the first minutes following flumazenil or midazolam administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109473 TI - The respiratory effects of reversing midazolam sedation with flumazenil in the presence or absence of narcotics. AB - The purpose of this study was to determine the effects of reversal of sedation with flumazenil (F), in the presence or absence of opiates, on arterial oxygen saturation (SaO2) and end-tidal CO2 (ETCO2). Twenty-four patients undergoing surgery and epidural anaesthesia were studied. Twelve patients (Group A) were orally premedicated with diazepam and 0.1 mg.kg-1 morphine i.m. Intraoperative sedation consisted of midazolam 0.1 mg.kg-1 and pethidine 0.7 mg.kg-1 i.v. Twelve patients (Group B) were premedicated with diazepam and sedated intraoperatively with 0.1 mg.kg-1 midazolam. In the recovery room, six patients in each group were randomly allocated to receive 1 mg of flumazenil while the others were allowed to awaken spontaneously (control). Sedation (eyes open vs closed), SaO2, ETCO2, respiratory rate, blood pressure and pulse were non-invasively monitored for 90 min. Administration of flumazenil resulted in a statistically significant increase in the number of patients with eyes open in both groups at 5 min, lasting 15 min in Group A and 30 min in Group B patients. An increase in SaO2 from 15-45 min after injection of flumazenil was observed only in Group B. No significant difference between groups in any other parameter was found. We concluded that reversal of benzodiazepine (BZ) sedation with flumazenil improved SaO2 in patients sedated with only BZ; in the presence of BZ and opiates, flumazenil did not affect respiratory parameters. PMID- 2109474 TI - Resedation. PMID- 2109475 TI - Cerebrovascular and metabolic effects of midazolam and flumazenil. PMID- 2109476 TI - Anaesthesia techniques for midazolam and flumazenil--an overview. AB - Midazolam, the latest benzodiazepine agonist, may be used in doses of 0.15 to 0.2 mg.kg-1 for induction of anaesthesia. It provides good correlation between plasma concentration and anaesthetic effect with an interindividual variability of only 20-25%. On this basis, dosage recommendations for midazolam in total intravenous anaesthesia techniques are possible, aiming at hypnotic plasma concentrations of at least 250 ng.ml-1. Due to its biological half-life of 150-180 min and interindividual differences in drug susceptibility, prolonged recovery periods have been observed that can safely and reliably be antagonised by flumazenil, if necessary. It is recommended that flumazenil be administered carefully by titration in increments of 0.1 mg.min-1 to avoid emergence reactions by awakening too fast (tachycardia, hypertension). Usually a mean total dose of 0.4-0.5 mg will lead to prompt awakening. PMID- 2109477 TI - Methohexital vs midazolam/flumazenil anaesthesia during laryngoscopy under jet ventilation. AB - In a randomised clinical study, two total intravenous anaesthesia techniques for microlaryngoscopic laser surgery were compared. After an induction dose of 100 mg methohexital, Group I received a maintenance infusion of 10 mg.min-1. In Group II anaesthesia was obtained by 15 mg midazolam followed by 0.1 mg.min-1 continuously and terminated by the injection of flumazenil. For analgesia 5 mg alfentanil were administered. Opiate-induced respiratory depression was antagonised by 0.08 to 0.12 mg naloxone. Prior to, during, and after surgery, adrenergic response was assessed by HPLC-analysis of blood taken from a peripheral vein. Haemodynamic responses to the operation and during the post-operative period were almost identical in both groups. In Group I, the mean recovery period of 14 min was significantly longer than in Group II (9 min), where patients received a mean dose of 0.53 mg (+/- 0.15) flumazenil. Resedation could be observed in all patients receiving flumazenil within 60 min after antagonisation, which was associated with a mean decrease in O2-saturation from 95% to 88%. There was no difference in epinephrine and norepinephrine blood levels between the two groups prior to and during anaesthesia. In all patients, arousal was associated with a significant increase in the epinephrine plasma concentration. While blood levels in Group I decreased during the post-operative period to levels prior to surgery, the concentrations in Group II remained elevated. In one patient who received no naloxone, the reversal of midazolam action induced a 16-fold increase in catecholamine levels (from 50 to 800 ng.l-1) associated with a tachycardia of 170 b.min-1 and hypertension of 160 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109478 TI - Midazolam and flumazenil in neuroanaesthesia. AB - Of the numerous benzodiazepines currently available, only a few are used in anaesthetic practice. Midazolam is utilised as a premedicant, sedative, and an induction agent and produces minimal depression of ventilation or of the cardiovascular system. The anticonvulsant activity is similar to that of diazepam. In neuroanaesthesia midazolam may be an acceptable alternative to other intravenous induction agents like barbiturates or etomidate in patients with compromised intracranial compliance. Midazolam produces dose-related reductions in cerebral blood flow and cerebral oxygen consumption. However, midazolam does not necessarily prevent increases in intracranial pressure during induction of anaesthesia. In the electroencephalogram (EEG) midazolam produces a reduction in alpha-activity, an increase in theta-delta-activity and low-voltage beta activity. Midazolam like other benzodiazepines does not affect early components of auditory and somatosensory evoked responses, whereas late cortical responses may be suppressed. Flumazenil, a specific benzodiazepine antagonist, has been demonstrated to be effective in reversing benzodiazepine-induced sedation. In the EEG midazolam-induced changes vanish almost instantaneously. Flumazenil is also effective in restoring the amplitudes of cortical auditory and somatosensory evoked responses. However, as has been demonstrated in head-injured patients and animal experiments after incomplete cerebral ischaemia, increases in cerebral blood flow and intracranial pressure cannot be excluded after flumazenil administration. When utilising flumazenil for wake-up procedures in midazolam sedated patients with pathological intracranial compliance, flumazenil has to be titrated very carefully in low doses over prolonged periods. PMID- 2109479 TI - Spleen versus CNS immunoglobulin G in multiple sclerosis: an isoelectric focusing study. AB - Immunoglobulin G (IgG) band patterns were investigated in a peripheral immune compartment, the spleen, and the central nervous system (CNS) compartment in 6 multiple sclerosis (MS) subjects and 3 controls in a search for systemic humoral immune response that may be related to the localized immune response seen in MS. Using the isoelectric focusing (IEF) technique with immunoperoxidase staining of proteins transferred to nitrocellulose membranes, we were not able to demonstrate any qualitative abnormalities of spleen or serum IgG in the MS cases, whilst all matched CNS tissues and CSF specimens were clearly positive for oligoclonal IgG bands. Our results suggest that there is no systemic oligoclonal IgG secretion in MS. This further supports the presence of a compartmentalized IgG intrathecal immune response in MS and emphasizes the organ specificity of MS. PMID- 2109480 TI - Intrathecal synthesis of immunoglobulin G in vascular dementia. AB - Serum and CSF from 53 vascular dementia (VD) patients and 50 controls were analysed to investigate the possibility of an intrathecal synthesis of IgG, defined as an elevated IgG index (greater than or equal to 7) and/or presence of oligoclonal IgG in cerebrospinal fluid (CSF), but not in serum. Five (9%) patients and no controls exhibited an intrathecal synthesis of IgG. The IgG index increased with the degree of dementia (p less than 0.05). It was positively related to presence/absence of hypertension (p less than 0.05) and correlated positively with diastolic blood pressure (p less than 0.05). The findings suggest that immunological factors might be involved in the pathogenesis of VD. PMID- 2109481 TI - Patterns of differentiation in central neurocytoma. An immunohistochemical study of eleven biopsies. AB - Central neurocytoma has been characterised by its intraventricular localisation, predominant occurrence in young adults, oligodendroglioma-like histology, benign course and ultrastructural evidence for neuronal differentiation. Eleven intraventricular central neurocytomas were studied histopathologically, employing cell type-specific immunocytochemical markers and electron microscopic analysis. In the past, these lesions have caused diagnostic problems since central neurocytomas share basic histopathological features with other periventricular neoplasms. Accordingly, several tumours of this series had previously been classified as ependymomas of the foramen of Monro or oligodendrogliomas. Although generally regarded as benign lesions, two central neurocytomas of this series showed histopathological evidence of anaplasia, with focal necrosis, mitotic activity and vascular proliferation. All central neurocytomas exhibited immunoreactivity for neuron-specific enolase and synaptophysin, indicating consistent neuronal differentiation. Three tumours were studied by electron microscopy and contained synaptic vesicles, neuritic processes and neurosecretory granules. In addition, one tumour contained ganglioid cells and this was associated with focal immunoreactivity for neurofilament protein, suggesting that some central neurocytomas may, at least focally, continue to differentiate towards the formation of mature neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109482 TI - Neuronal inputs to hippocampal formation in Alzheimer's disease and in parkinsonism-dementia complex on Guam. AB - This study concerns the expression of synaptophysin in the hippocampal formation of normal controls, of patients with Alzheimer's disease (AD) and of patients with parkinsonism-dementia complex on Guam (P-D complex). A monoclonal antibody was used to visualize synaptophysin, an integral component of presynaptic vesicle membranes. In the normal controls, a strong synaptophysin immunoreactivity was seen in the stratum pyramidale, stratum radiatum and stratum lacunosum-moleculare of the hippocampus proper, in the subiculum and in the molecular layer of the dentate gyrus. In the dentate gyrus molecular layer, the reaction product was distributed in a laminar fashion. By contrast, in AD and in P-D complex a significant decrease in immunoreactivity was observed in all hippocampal strata, and especially of the hippocampal subfield CA1 and the subiculum. In both diseases, synaptophysin expression was also diminished in the molecular layer of the dentate gyrus of all patients examined, with the inner portion exhibiting almost normal and the outer portion a strikingly reduced synaptophysin immunoreactivity. PMID- 2109483 TI - Lung development, surfactant and respiratory distress syndrome. PMID- 2109484 TI - Antibody-dependent cellular cytotoxicity and natural killer activity against HTLV 1 infected cells. AB - Antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) activity were examined using MT-2 cells persistently infected by HTLV-1 as target cells, and mononuclear cells as effector cells, from healthy one-week-old newborn babies, infants, children and adults. More than 10% of ADCC was observed in 17 newborn babies out of 22 (77.3%) and in all 67 healthy one-month-old babies to adults, by adding serum from anti-HTLV-1 positive carriers. When anti-HTLV-1 negative serum was added, less than 10% of ADCC was observed. If infants without anti-HTLV-1 antibodies were breast-fed they had the possibility of HTLV-1 vertical transmission. There was no significant decrease in NK activity between 90 healthy newborn babies, infants, children, or adults. These results suggest that ADCC and NK activity protect against the transmission of HTLV-1 from mother to child. PMID- 2109485 TI - Biochemical pathogenesis of demyelination in globoid cell leukodystrophy (Krabbe's disease): the effects of psychosine upon oligodendroglial cell culture. AB - The effects of psychosine on the metabolism of myelin associated glycolipids such as galactocerebroside and sulfatide in mouse brain cell cultures were investigated in order to clarify the mechanism of demyelination in globoid cell leukodystrophy (Krabbe's disease). The incorporation of 3H-galactose into cerebroside and sulfatide was studied in the presence of psychosine (1-3 micrograms/ml medium). These data indicated that psychosine inhibited the incorporation of 3H-galactose into cerebroside and sulfatide not in astroglial cell culture but in oligodendroglial cell culture. Oligodendrocytes produce myelin in the central nervous system, and cerebroside and sulfatide are major components of myelin. These results suggest that psychosine influences the lipid metabolisms of myelin and subsequently leads to the demyelination in Krabbe's disease. PMID- 2109486 TI - Pancreatic hormone changes in infantile obstructive jaundice. AB - Metabolic disturbances of pancreatic hormones in obstructive jaundice in infancy were evaluated experimentally and clinically. In our experimental study, using young rats, the level of plasma insulin (IRI) gradually increased after ligation of the common bile duct. These levels were a little lower than those in the non treated controls. The level of plasma glucagon (IRG) increased remarkably 4 weeks after ligation of the common bile duct. Clinically, there were no significant differences in the levels of IRI and IRG among normal controls and cases of neonatal hepatitis and congenital biliary atresia (CBA). In CBA patients, these levels can be correlated with the progression of hepatic fibrosis; an increase in IRG and a decrease in the IRI/IRG mol ratio was noticed in patients with grade III of hepatic fibrosis. These results indicate that, in obstructive jaundice in infancy, the more severe the hepatic damage due to obstructive jaundice, the higher the level of plasma glucagon concentration will rise. PMID- 2109487 TI - Age-related changes in urinary growth hormone level and its clinical application. AB - In order to establish the normal range of urinary growth hormone (GH) level for age and sex, which is important in the clinical application of urinary GH to diagnosis, we measured GH in the first morning urine specimens of 270 normal subjects aged 3 to 20 years. Urinary GH levels in patients with documented GH deficiency were compared with those of the normal controls. In normal subjects, urinary GH levels showed a statistically significant change with age. They were relatively high in infancy and mid-puberty, reaching a peak at 11 to 12 years in girls and at 13 to 14 years in boys. Urinary GH levels in patients with complete GH deficiency were apparently lower (less than -2.0 SD) than those of the normal children, while the levels in patients with partial GH deficiency overlapped with the normal range. When assessing GH secretion by using urinary GH measurement, consideration of age and sex is required, since the level changes significantly with these factors. PMID- 2109488 TI - Renal osteodystrophy in patients on continuous ambulatory peritoneal dialysis. AB - Twelve patients on continuous ambulatory peritoneal dialysis (CAPD) were studied in order to evaluate the progression of renal osteodystrophy (ROD). All patients received doses of 0.01-0.02 microgram/kg of 1 alpha vitamin D3 (1 alpha-D3) and 0.1-0.15 g/kg of calcium carbonate for 12-18 months. Serum total protein, total calcium (Ca), creatinine, inorganic phosphate, alkaline phosphatase (ALP), and n terminal parathyroid hormone were measured regularly. The radiological bone appearance for ROD or rickets and the height standard deviation score were compared between the outset and the end of this study. An increase of Ca values and a decrease of ALP values correlated with a suppression of hyperparathyroidism, and the hyperphosphatemia was controlled in the majority of our patients throughout this study. Two patients had ROD and rickets at the outset of this study, and all patients but one had neither ROD nor rickets at the end of this study. Growth retardation improved or remained stable in 10 patients. Our results indicate that adequate doses of 1 alpha-D3 and calcium carbonate are effective in the prevention of ROD and rickets in patients on CAPD. PMID- 2109489 TI - The third nationwide survey in Japan of vitamin K deficiency in infancy. AB - The occurrence of hemorrhagic disease due to vitamin K (VK) deficiency beyond the neonatal period has come under investigation in Japan. In 1980 the 1st nationwide survey was conducted in Japan by Nakayama and others, and was followed by the 2nd nationwide survey in 1985 by Hanawa. The present survey was designed to further monitor the incidence of this disease in Japan during the 3-year period from July 1985 to June 1988. Questionnaires were sent to 1,315 hospitals having more than 200 beds, located throughout Japan. Responses were received from 775 hospitals, for an answer rate of 58.9%. The total number of reported cases was 175, including 129 idiopathic type, 28 secondary type and 18 near-miss type. In this survey it was revealed that the incidence rate of the idiopathic type of vitamin K deficiency in infancy (VKDI) has decreased remarkably, to about one-fourth that reported in the first survey. The declining incidence rate of VK deficiency in Japan is considered to be the result of ever more widespread prophylactic administration of VK during the neonatal period, as most occurrences of VK deficiency in infancy are preventable by prophylactic administration of VK from the neonatal period. However, in 16 cases of the idiopathic type of VK deficiency found in the present survey, VK had been administered at least once during or after the neonatal period. This shows the heterogeneity of this condition. PMID- 2109490 TI - A rubella epidemic in Sasebo, Japan in 1987, with various complications. AB - Though the rubella vaccination programme for adolescent girls was introduced in Japan in 1977, rubella epidemics have occurred repeatedly. Also in Sasebo, Japan in 1987, we experienced various complications as follows: encephalitis (five cases), meningitis (three), thrombocytopenic purpura (four), vascular purpura (four), hemolytic anemia (two), pneumonia (eight), protein-losing gastroenteropathy (one), multiple organ disorder with encephalitis, purpura, myocarditis, hepatic and renal dysfunction (one), and congenital rubella syndrome (CRS: three). Disorders ranging over multiple organs seem to occur in acquired as well as congenital rubella infection. The incidence of encephalitis was estimated to be 1:1600 cases of rubella and two of five cases were apparently serious. Though the strategy for preventing rubella has been directed only against CRS, we should note the various and severe complications with acquired rubella infection, and should adopt two-stepped protection: vaccination of young children of both sexes and of adolescent girls. PMID- 2109491 TI - Organic acid and acylcarnitine profiles of glutaric aciduria type I. AB - Urinary organic acid and acylcarnitine profiles from a 2-month-old boy were studied by gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry. The patient excreted large amounts of glutaric acid and significant amounts of 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine, and his serum glutaric acid level was markedly elevated. Thus he was chemically diagnosed as having glutaric aciduria type I (GAI). In addition to the above metabolites previously described in GAI, significantly increased excretion of 2-ketoglutaric acid, succinic acid, adipic acid, adipylcarnitine, suberic acid and azelaic acid was found. 2-Ketoadipic acid methylsuccinic acid and ethylmalonic acid were also detectable, suberylcarnitine was not increased, and dehydroadipylcarnitine was decreased in his urine. These results suggest that excess glutaryl-CoA causes the competitive inhibition of the dehydrogenation of adipyl-CoA to dehydroadipyl-CoA and results in an increase of adipic acid and adipylcarnitine and a decrease of dehydroadipylcarnitine. It is also suggested that oxidative decarboxylation of 2 ketoglutaric acid to succinyl-CoA is inhibited by high levels of glutaryl-CoA, and that the dehydrogenation of succinic acid to fumaric acid is inhibited owing to the increased glutaric acid derived from excess glutaryl-CoA. These results indicate that gas chromatography-mass spectrometry is the most appropriate and accurate method for the differential chemical diagnosis of GAI and glutaric aciduria type II. PMID- 2109492 TI - Central nervous system sequelae of immunization against measles, mumps, rubella and poliomyelitis. PMID- 2109493 TI - Terminal deletion of chromosome 10q and its clinical features. AB - A male case with terminal deletion of chromosome 10q has growth retardation, craniofacial dysmorphism, congenital heart disease and other minor anomalies. The karyotypic formula is 46, XY, del (10), (q26.1----qter) by a high resolution G banding staining. There are few differences in clinical features between our case and the previously reported cases. PMID- 2109494 TI - Precocious puberty in a seven-year-old boy due to human chorionic gonadotropin producing pineal tumor detected by nuclear magnetic resonance computed tomographic scanning. AB - We report a 7-year-old boy who developed incomplete sexual precocity due to a human chorionic gonadotropin (HCG)-producing tumor in the pineal region. The patient presented enlarged testes (3 x 2 x 2 cm) bilaterally, enlarged penis, pubic hair development of Tanner Stage III, advanced bone age and growth spurt. Initial hormonal studies showed an adult male level of testosterone (13 ng/ml) and a high level of HCG as well as HCG-beta subunit. A high basal level of LH, probably due to immuno-cross-reactivity with HCG, and low basal level of FSH, probably suppressed by testosterone, did not respond to LH-RH infusion. Search for the site of HCG production failed at the initial workup, but calcification without definite signs of tumor in the pineal region was found by conventional brain CT scan. Because of subsequent progression of clinical and laboratory findings of sexual precocity, nuclear magnetic resonance computed tomographic (NMR-CT) scan was performed, which confirmed the presence of a pineal tumor three months later. The patient was treated with 4,500 rad. of radiation therapy, and responded dramatically to this regimen. He has been followed for more than two years without any signs of recurrence. We have reported here a very rare case of incomplete sexual precocity due to an HCG-producing intracranial tumor in the pineal region. An NMR-CT scan is a very useful tool for the diagnosis of some types of pineal tumor, such as germinoma, which are highly radiosensitive. PMID- 2109495 TI - Supraventricular tachycardia in acquired rubella infection: a case report. AB - A 6-year-old boy developed supraventricular tachycardia nine days after onset of the exanthem of clinical rubella. The diagnosis of rubella virus infection was confirmed serologically. Except in the neonatal period, only eight cases of cardiac involvement in acquired rubella infection have been previously reported. During epidemics, rubella virus infection should be considered in patients who manifest cardiac symptoms and signs of unknown etiology. PMID- 2109496 TI - The influence on the breathing pattern in man of moderate levels of continuous positive and negative airway pressure and of positive end-expiratory pressure during air and CO2 inhalation. AB - The purpose of this study was to determine in man the effect on the breathing pattern of continuous positive (CPAP), continuous negative (CNAP) and positive end-expiratory (PEEP) airway pressure during air breathing and CO2 inhalation. Six subjects were exposed to CPAP, CNAP and PEEP 0.5 kPa, while five subjects were exposed to CPAP and CNAP 0.8 kPa. End-expiratory lung volume increased during CPAP 0.8 kPa and decreased during CNAP 0.8 kPa. CPAP induced more extensive changes in the ventilatory pattern, and the changes in each parameter were larger than observed during CNAP and PEEP at the same pressure level. In contrast to previous reports we found the effect of CO2 inhalation combined with the effect of pressure breathing to be not stronger than additive. Even moderate CPAP induced alveolar hyperventilation with marked reduction in arterial PCO2 (PaCO2) when breathing air. With increasing fraction of CO2 in the inspiratory gas, the difference in PaCO2 between CPAP and no CPAP disappeared. PEEP also affected the breathing pattern in that it induced an increase in mean inspiratory flow and mean expiratory flow and a reduction in inspiratory duration. Occurrence of ventilatory pauses depended on whether mouthpiece or facemask was used. CPAP and CNAP did not influence the occurrence of pauses, while PEEP prolonged post expiratory pauses. We conclude that CPAP, CNAP and PEEP induce active ventilatory responses in man and that strong mechanisms are involved during CPAP since PaCO2 is markedly reduced. PMID- 2109497 TI - Diagnostic and therapeutic value of testing stimulation of thyroid-stimulating hormone by thyrotropin-releasing hormone in 100 depressed patients. AB - The thyrotropin-releasing hormone (TRH) test was performed in 100 depressed patients, including 73 patients with a major depressive episode (MDE) according to DSM-III. Thirty-one patients subsequently received an antidepressant with a predominant serotoninergic action (indalpine or citalopram), and 27 patients received a noradrenergic antidepressant (maprotiline). The diagnostic value of the TRH test was not conclusive for any of the subgroups of depressed patients: MDE, MDE with melancholia or MDE in bipolar patients. Similarly, the value of the TRH test in the choice of antidepressant treatment according to the monoaminergic action was not convincing. These results are discussed in the light of the data of the international literature. PMID- 2109498 TI - A multicentre double-blind comparative trial of fluvoxamine versus lorazepam in mixed anxiety and depression treated in general practice. AB - Fluvoxamine, a selective serotonin reuptake inhibitor, was compared with lorazepam in a multicentre double-blind, parallel group study in 112 general practice patients with mixed anxiety and depression. For inclusion, patients were required to have minimum baseline scores of 21 on the Montgomery-Asberg Depression Rating Scale (MADRS) and 11 on the Clinical Anxiety Scale (CAS). Treatment was for 6 weeks. There were no significant differences between treatments at any point except in an elderly subgroup in whom anxiety improved more rapidly with lorazepam. There were significant improvements in MADRS, CAS and global ratings compared with baseline at all subsequent assessments. Improvement continued during the whole treatment period. Lorazepam produced more sedation, whilst fluvoxamine produced significantly more nausea and vomiting; this was usually early in onset and, if tolerated, resolved during the course of the study. As it is now widely recognized that benzodiazepines should only be given in short courses of 2-4 weeks, the continued improvement up to 6 weeks has implications regarding choice of treatment. PMID- 2109499 TI - In vitro screening for anticonvulsant-induced teratogenesis in neural primary cultures and cell lines. AB - To establish inherent potential for the induction of neural tube defects the ability of selected anticonvulsant agents to interfere with cell division has been established in vitro using an antiproliferative assay in clonal cell lines and a cytotoxicity assay using primary cultures of cerebral cortex neurons at different stages of development. In order to evaluate the relative toxicities of these agents their in vitro effects were determined at 2-3 times the plasma therapeutic level. By these procedures valproate and the benzodiazepines, diazepam and clonazepam, exerted a potent antiproliferative action which could not be attributed to increased cytotoxicity. In contrast phenytoin was markedly cytotoxic but was without an antiproliferative action. This cytotoxicity was most pronounced during the periods of extensive fibre outgrowth. When compared to epidemiological and animal study data, agents which inhibited cell proliferation within twice therapeutic concentration were consistently associated with major neural tube malformations. However phenytoin, found to be positive in the cell cytotoxicity assay, is not associated with neural tube malformations but rather is primarily associated with mental retardation. Thus assessment of antiproliferative activity of anticonvulsant drugs may be one criterion for identification of teratogenic potential during neurulation. PMID- 2109500 TI - Endotoxins of Pseudomonas fluorescens. PMID- 2109501 TI - Lipoamino acids which are similar to bacterial endotoxin in both structure and biological activity related to physiological function. PMID- 2109502 TI - Development of a new quantitative method for detection of endotoxin by fluorescence labeling of 3-hydroxy fatty acid. AB - New quantitative method for the detection of minute amounts of endotoxin has been developed using 3-hydroxytetradecanoic acid as a chemical marker. After converting 3-hydroxytetradecanoic acid to methyl ester, it was coupled with a fluorescent probe, anthracene-9-carboxyl chloride, obtained by chlorization of 9 anthroic acid with oxalyl chloride. The resulting ester was isolated by HPLC on silica column. The purified product, methyl-3-0-(9-carboxy-anthracenyl) tetradecanoate (M/Z 462), was highly responsive to a fluorescence spectrophotometer, showing maximum emission with excitation wavelength at 257 nm and emission wavelength at 458 nm in dichloromethane, the limit of detection being as little as 10 f mol. Using this method it is currently possible to detect Salmonella abortus equi endotoxin in aqueous solution at a level of 100 pg. PMID- 2109503 TI - Biological activities of anti-LPS factor and LPS binding peptide from horseshoe crab amoebocytes. PMID- 2109504 TI - Primary structures and functions of anti-lipopolysaccharide factor and tachyplesin peptide found in horseshoe crab hemocytes. PMID- 2109505 TI - Further characterization of monoclonal antibodies to lipopolysaccharide of Salmonella Minnesota strain R595. AB - We have shown here that despite the use of monoclonal antibodies with well defined epitope-specificities, and despite testing them in the most simple animal model available (i.e., mixing of homologous LPS with Mab prior to injection), we are not yet able to explain why some of the antibodies were effective and others not. For some of the clones (e.g., clone 20), an even better definition of binding sites is currently taking place in an attempt to obtain this understanding. We also do not yet understand why clone 20 was not effective in the mucin model, while using much lower amounts of injected antibody, and much higher challenge doses, this Mab was effective against E. coli in the gentamicin treated mouse model. Very clear is, however, that in order to be protective in the latter model, Mabs are not required to be specific for lipid A. In the future it will be essential to develop procedures which measure specific interaction between smooth LPS/bacteria and antibodies to the LPS core region. In addition, it will be of great help when the chemical structure of non-substituted, rough form LPS, as occurring in smooth LPS preparations, would be defined. This applies also to O-substituted core molecules. PMID- 2109506 TI - The role of 13-hydroxylinoleic acid in the activation of macrophages by lipopolysaccharide. PMID- 2109507 TI - Mechanisms of endotoxin stimulation of monocytes in whole blood. PMID- 2109508 TI - Lipopolysaccharide-induced priming of the murine macrophage-like cell line J774A.1 for enhanced production of reactive oxygen intermediates is blocked by antiserum to murine interferon beta. PMID- 2109509 TI - Comparison of endothelin-1 and -3 on models of inflammation. PMID- 2109510 TI - The in vivo and in vitro anti-inflammatory activity of CD271: a new retinoid-like modulator of cell differentiation. PMID- 2109511 TI - The effect of retinoids on the skin reaction and swelling seen 7 days after adjuvant injection in the rat paw. PMID- 2109512 TI - Arachidonic acid induced ear oedema in four strains of rats and mice: a comparative study of anti-inflammatory drugs. PMID- 2109513 TI - Disease in children due to serogroup W-135 Neisseria meningitidis. AB - Two cases of meningococcal disease due to serogroup W-135 Neisseria meningitidis are presented. One died from fulminating meningococcaemia and the other had severe meningoencephalitis with acute septic arthritis. Serogroup W-135 N. meningitidis is pathogenic for man, and laboratories should attempt to identify and serotype the organism so that more data about the disease it causes can be obtained. PMID- 2109514 TI - Is enteric Staphylococcus a causative agent of skeletal muscle abscesses in children? AB - In a study of 46 children under the age of 10 years treated for pyogenic muscle abscesses, stool culture revealed Staphylococcus aureus in association with malnutrition, gastrointestinal infections and weaning. Naturally occurring protease-inhibitors were associated with the diets of these children along with poor standards of food hygiene. A study on 60 healthy age-matched controls showed a significant increase in the stool culture yields of S. aureus during weaning onto a traditional solid diet. It is probable that the bacterial overgrowth in the bowel in these states is associated with the development of muscle abscesses caused by this organism. PMID- 2109516 TI - Total phospholipid choline concentration of amniotic fluid in the assessment of foetal gestational and lung maturity. I. Establishment of a direct enzymic method. AB - An enzymic assay of the choline-containing phospholipids of amniotic fluid which does not require lipid solvent extraction has been developed. Lecithin and sphingomyelin are the dominant phospholipids in mature lung surfactant. The total phospholipid choline content of amniotic fluid, which represents the molar sum of lecithin and sphingomyelin, may be expected to correlate with foetal lung maturity. The merits of our new analytical method of determination of total phospholipid choline concentration in amniotic fluid are discussed. PMID- 2109515 TI - A comparative study of three oral contraceptives in Ibadan: Norinyl 1/35, Lo Ovral and Noriday 1/50. AB - A study of three combined oral contraceptives, Norinyl 1/35, Lo-Ovral and Noriday 1/50, was conducted at the University of Ibadan Teaching Hospital, Ibadan, Nigeria, to determine if there were differences in continuation rates and reasons for discontinuation. This report includes analysis of 150 women, all of whom were interval patients, randomly allocated to one of the above oral contraceptives between May 1984 and February 1985. Follow-up visits were scheduled at 1, 4 and 8 months after admission. Significantly more women in the Norinyl 1/35 group (P less than 0.05) reported intermenstrual bleeding, as well as an increase in the occurrence of intermenstrual bleeding compared to women in the Lo-Ovral group. There were no other differences between the groups for side-effects. The continuation rates at 8 months were 90.8% for the Norinyl 1/35 group, 94.4% for the Lo-Ovral group and 87.1% for the Noriday 1/50 group. The corresponding rates for those lost to follow-up were 26.0, 40.8 and 17.7. The rate for total discontinuations (all discontinuations including women lost to follow-up) was 34.0% for the Norinyl 1/35 group, 44.9% for the Lo-Ovral group and 29.4% for the Noriday 1/50 group. There was a significant difference in lost to follow-up rates between the Lo-Ovral group and the Noriday 1/50 group (P less than 0.05). There were no other significant differences between the groups for life table rates (P greater than 0.05). There were no pregnancies reported during the study period. PMID- 2109517 TI - Total phospholipid choline concentration of amniotic fluid in the assessment of foetal gestational and lung maturity. II. Correlation study. AB - Analysis of total phospholipid choline concentration was carried out on amniotic fluid samples obtained from 20 pregnant Nigerian women in established labour to determine the correlation of amniotic fluid phospholipid choline concentration with the gestational ages and maturity of the infants. There was a positive correlation between phospholipid choline concentration and gestational age. All infants whose gestational ages were estimated to be over 36 weeks had a total phospholipid concentration greater than 50 mumols/l. Four infants whose gestational ages were less than 36 weeks had total phospholipid choline concentration less than 30 mumols/l. None of these infants showed any evidence of Respiratory Distress Syndrome. PMID- 2109518 TI - Insulin secretory reserve in diabetic Nigerian Africans. AB - The insulin secretory capacity of three groups of Nigerian African diabetics was assessed by measuring the concentration of C-peptide before and after stimulation with oral glucose. Group 1 subjects had a history of keto-acidosis and were treated with insulin. Those in group 2 had no history of keto-acidosis but required insulin to normalize blood glucose while those in group 3 also had no history of keto-acidosis and were treated with diet alone or in combination with oral hypoglycaemic drugs. C-peptide levels (mean +/- s.e.m.) showed group 1 subjects to be insulin deficient (fasting 0.08 +/- 0.04 pmol/ml, peak 0.14 +/- 0.03 pmol/ml), group 2 to have reduced insulin secretion (fasting 0.16 +/- 0.01 pmol/ml, peak 0.35 +/- 0.01 pmol/ml) and group 3 to have a moderately reduced fasting insulin and a higher peak insulin secretion (fasting 0.27 +/- 0.03 pmol/ml, peak 1.49 +/- 0.4 pmol/ml) compared with a non-diabetic control group (fasting 0.30 +/- 0.03 pmol/ml, peak 1.16 +/- 0.1 pmol/ml). Although the aetiology of diabetes in the Nigerian African is unclear, a spectrum of the disease exists which is similar to that in Caucasian population. PMID- 2109519 TI - Uraemia and adrenocortical function in Nigerian subjects. AB - In assessing the pituitary-adrenal axis of uraemic Nigerians, we investigated the circadian rhythm of plasma cortisol secretion, the response to the overnight dexamethasone (1 mg) suppression test and the pattern of excretion of urinary free cortisol (UFC) in 10 uraemic subjects and nine non-uraemic controls. Basal (0800 h) plasma cortisol levels were similar in both uraemic (mean +/- s.e.m.; 224 +/- 36 nmol/l) and non-uraemic (218 +/- 47 nmol/l) subjects. The non-uraemic subjects demonstrated the normal late night (2300 h) reduction in cortisol levels but this was absent in uraemic subjects in whom the basal and late night values were similar. Post-dexamethasone (0800 h) values were suppressed by 80% in non uraemic subjects (P less than 0.01) from 218 +/- 47 nmol/l (at 2300 h) to 44 +/- 16 nmol/l (at 0800 h), whereas there was lack of suppression (P greater than 0.05) in values from uraemic subjects (224 +/- 36 nmol/l at 2300 h and 210 +/- 39 nmol/l at 0800 h). Irrespective of the degree of renal impairment in uraemic subjects, the 24 h UFC excretion was significantly greater (P less than 0.05) (1126 +/- 403 nmol/24 h) compared with non-uraemic subjects (342 +/- 94 nmol/24 h). These results confirm previous observations in Caucasians and reaffirm the existence of a pseudo-Cushingoid state in uraemia which may contribute to the associated hypertension and electrolyte abnormalities. PMID- 2109520 TI - Morbidity trends at the children's emergency room, University College Hospital, Ibadan, Nigeria. AB - The paper describes the pattern of diseases of the 17,033 emergency admissions at the children's emergency room of the University College Hospital, Ibadan. Neonates and infants constitute 60% of admissions into the children's emergency room although the facilities provided are heavily weighted in favour of older children. The study also shows a high prevalence of infectious diseases the commonest of which include measles and meningitis. The implications for hospital management of the low frequency of admissions over the weekends and high frequencies in the months of January to April in terms of staff adjustment and facilities are discussed. PMID- 2109521 TI - Effects of cows' urine concoction with and without tobacco leaves on plasma glucose concentration in fasted rats. AB - The effects of a full preparation (FP) and a modified preparation (MP) of cows' urine concoction (CUC) on the level of plasma glucose in fasted male Wistar rats were investigated. The results showed that FP caused significant hyperglycaemia; while the MP and a control injection using 0.9% saline had no effect on plasma glucose. Hexamethonium, prazosin, propranolol and combined prazosin and propranolol did not abolish the hyperglycaemic response to FP. The mechanism of the hyperglcaemic response to FP and the reason why MP did not produce hypoglycaemia are obscure. The result of this study did not agree with the findings of CUC-induced hypoglycaemia reported by earlier workers. PMID- 2109522 TI - Assessment of a fixed-dosage combination of atenolol and chlorthalidone (Tenoretic) in hypertensive Nigerians. AB - The antihypertensive effect of a fixed dosage combination of the cardioselective beta-adrenoceptor blocker, atenolol, and the oral thiazide-like diuretic, chlorthalidone (Tenoretic) was studied in 24 hypertensive Nigerians in a double blind, cross-over comparison with three other treatments. These were atenolol alone, 100 mg daily, chlorthalidone alone, 25 mg daily, and atenolol (100 mg) plus chlorthalidone (25 mg) daily taken as separate formulations. Tenoretic was taken as a once-daily tablet containing 100 mg atenolol plus 25 mg chlorthalidone. The order of administration of the drugs was randomized. Each drug was taken for 4 weeks. The results showed that atenolol and chlorthalidone lowered blood pressure to the same extent. Combination of the two drugs whether taken separately or in fixed-dosage combination was better than either product singly. The drugs were well tolerated. PMID- 2109523 TI - Coronary angioplasty in acute MI. Part 1. PMID- 2109524 TI - Cardiac morphologic findings in patients with acute myocardial infarction treated with recombinant tissue plasminogen activator. AB - The hearts of 52 patients (aged 61 +/- 11 years, 34 men) who participated in the Thrombolysis in Myocardial Infarction (TIMI) Study and died from 5 hours to 260 days (median 2.7 days) after onset of chest pain were studied. One heart became available at cardiac transplantation. Of the 52 patients, 38 received recombinant tissue plasminogen activator (rt-PA) not followed by percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). Eight had PTCA, and 6 had CABG. The infarcts were hemorrhagic by gross inspection (with histologic confirmation) in 23 patients, nonhemorrhagic in 20, not visible grossly in 2 and, in 7, there was no myocardial necrosis by either gross or histologic examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109525 TI - Kappa immunoglobulin light chain gene rearrangement in a T-lineage chronic lymphocytic leukemia. AB - Until recently, only B-lineage lymphoid cells were observed to rearrange kappa immunoglobulin light chain genes. The authors examine peripheral blood mononuclear cells from a patient with chronic lymphocytic leukemia. More than 90% of these cells bound T-lymphocyte specific antibodies, failed to bind B lymphocyte specific antibodies, had rearranged T-cell receptor beta-chain genes and had retained immunoglobulin heavy chain genes in the germline configuration. Despite these T-lineage markers, the majority of these cells had rearranged kappa immunoglobulin light chain genes. This provides the first conclusive evidence for rearranged kappa genes in malignant T-lineage cells and warns that gene rearrangement studies alone cannot indicate tumor cell lineage. To detect T lineage cells that rearrange immunoglobulin genes, multiple immunophenotypic and genotypic parameters must be evaluated. These cells may provide important models to study how normal and malignant cells rearrange lymphocyte receptor genes. PMID- 2109526 TI - Colloidal bismuth subcitrate inhibits peptic degradation of gastric mucus and epidermal growth factor in vitro. AB - The effect of an antiulcer drug, colloidal bismuth subcitrate (De-Nol), on the proteolytic activity of pepsin toward gastric mucus and salivary epidermal growth factor was investigated. Samples of pig gastric mucus and mouse epidermal growth factor were incubated with pepsin in the absence and in the presence of De-Nol, and the released alpha-amino acid residues were quantified. Results of analysis revealed that, in the absence of De-Nol, the apparent Km value of pepsin toward gastric mucus was 1.4 g/L and that towards epidermal growth factor 120 microM. Introduction of De-Nol to the incubation mixtures led, in both cases, to reduction of the rates of proteolysis. With gastric mucus, the rate of proteolysis inhibition was proportional to the De-Nol concentration up to 1 x 10( 2) g/L, at which point a 54% reduction in mucus proteolysis occurred, whereas, with epidermal growth factor, this concentration of De-Nol caused nearly 52% inhibition in the rate of proteolysis. The apparent Ki value for peptic degradation of gastric mucus in the presence of De-Nol was 2.1 x 10(-4) g/L and that for peptic degradation of epidermal growth factor 1.8 x 10(-2) g/L. The results suggest that among the beneficial effects of colloidal bismuth subcitrate on ulcer healing is its ability to interfere with peptic digestion of the protective gastric mucus coat and of such important bioactive protein as epidermal growth factor. PMID- 2109527 TI - The "buried bumper syndrome": a complication of percutaneous endoscopic gastrostomy. AB - Percutaneous endoscopic gastrostomy is used for long-term nutritional support and can be performed with relatively few complications. We describe a patient in whom the internal bumper eroded into the stomach wall and was completely covered by gastric epithelium 11 months after gastrostomy tube placement. The gastrostomy tube itself was patent, and the end still protruded into the lumen of the stomach so that tube feeding was not impaired. Endoscopy, in combination with passage of Savary dilators over a guidewire, was safely used to remove the gastrostomy tube and buried bumper. We recommend this approach in patients with the "buried bumper" syndrome to prevent continued tube migration into the gastric and abdominal walls. PMID- 2109528 TI - Nutrition, survival, and AIDS. PMID- 2109529 TI - Surface light chain phenotype in indolent lymphomas: lack of prognostic significance. AB - The indolent follicular and diffuse lymphomas are neoplasms of B-cell origin. In several other B-cell neoplastic disorders, including multiple myeloma, hairy cell leukemia, and chronic lymphocytic leukemia, the light chain isotype of the surface immunoglobulin has been reported to have prognostic significance. Patients with tumors expressing lambda light chains usually fare more poorly than those with kappa light chain-bearing tumours. We analyzed the clinical data and immunologic phenotype of 101 patients with indolent lymphoma. Eighty-nine of the 101 patients demonstrated surface immunoglobulin of only one light chain type (kappa-47, lambda-42). Patients in both groups were matched for known prognostic factors. There were no significant differences in disease-free survival or overall survival between the two groups or within histologic subtypes. These results indicate that the immunologic light chain phenotype in indolent lymphoma, unlike other B-cell neoplasms, is not a prognostic indicator of survival. PMID- 2109530 TI - Enhancement of sickle erythrocyte adherence to endothelium by autologous platelets. AB - The increased adhesiveness of sickle erythrocytes (SS RBC) to endothelial cells has been confirmed in a static system utilizing fresh umbilical vein endothelium. Adherence of SS RBC to the endothelium was as great in the presence of calcium containing buffer as when incubated in plasma. SS RBC suspended in autologous platelet-rich plasma adhered to a greater extent than when suspended in autologous platelet poor plasma. Prostacyclin, thromboxane B2, and an inhibitor of collagen- and epinephrine-induced platelet aggregation (B13.177) did not affect SS RBC adherence to endothelium. Aspirin in a concentration of 5 micrograms/ml slightly decreased SS RBC adherence to endothelium in the presence of platelets. Platelets may play a significant role in the increased adhesiveness of SS RBC to endothelium. To the extent that increased SS RBC adhesiveness contributes to the genesis of painful crises and to the extent platelets augment this adhesiveness, agents affecting platelet function may prove useful in preventing painful crises. PMID- 2109531 TI - Recombinant gamma interferon in treatment of patients with atopic dermatitis and elevated IgE levels. AB - PURPOSE: Recombinant gamma interferon (rIFN-gamma) inhibits IgE synthesis in vitro by human peripheral blood mononuclear cells (PBMC). These data suggest a role for rIFN-gamma in the treatment of patients with severe atopic dermatitis (AD) and elevated IgE levels. The purpose of this study was to determine the effect of rIFN-gamma treatment on IgE production in patients with AD. PATIENTS AND METHODS: Twenty-two patients with chronic severe AD were treated with rIFN gamma. In part I of the study, 14 patients were treated with daily subcutaneous injections at three successive dose levels (0.01 mg/m2, 0.05 mg/m2, and 0.1 mg/m2) for 5 days with 2 days off between each dose level. In part II, eight patients received rIFN-gamma at 0.05 mg/m2, daily for 6 weeks. One patient from part I and eight patients from part II of the study received three times per week maintenance thereby for up to 14 months. Prior to and at selected times during and after treatment, the clinical and immunologic status of the patients was assessed. RESULTS: In part I, spontaneous de novo IgE synthesis by PBMC was inhibited in 10 patients receiving rIFN-gamma at 0.01 mg/m2 (p = 0.038) and in nine at 0.1 mg/m2 (p = 0.066). There was no reduction of serum IgE levels at any of the three dose levels. Total clinical severity showed improvement at each dose level (p less than 0.04) with worsening 3 days after discontinuation of treatment. In part II, there was no significant inhibition of spontaneous IgE synthesis by PBMC nor was there any reduction of serum IgE. Nevertheless, there was a progressive and significant reduction (p less than 0.01) in total clinical severity over the 6 weeks of daily rIFN-gamma with a sustained improvement during maintenance therapy. CONCLUSION: The results of this pilot study suggest that rIFN-gamma may be efficacious in the treatment of AD and that further clinical trials are warranted. PMID- 2109533 TI - J chain disease: an aggressive evolution of multiple myeloma. PMID- 2109532 TI - J. chain disease: a novel form of plasma cell dyscrasia. PMID- 2109534 TI - Intrauterine transfusion--intraperitoneal versus intravascular approach: a case control comparison. AB - Intravascular fetal transfusion has gained widespread acceptance and has supplanted the use of intraperitoneal fetal transfusion in management of severe alloimmune disease in many centers. This study compares the two methods with regard to multiple objective end points of performance, therapy, and outcome in a highly matched case-control fashion. The intravascular approach is better on almost every level. More surviving infants who are in better condition at a mature gestation and whose mothers have fewer complications and sequelae are the result. Whereas intraperitoneal transfusion should not be abandoned altogether, it is a second-line procedure used only in very limited circumstances. Intravascular fetal transfusion offers realistic prognosis for intact survival at virtually any extreme of alloimmune disease. PMID- 2109535 TI - Prediction of fetoplacental blood volume in isoimmunized pregnancy. PMID- 2109536 TI - Pathophysiology of antiphospholipid antibodies: absence of prostaglandin-mediated effects on cultured endothelium. AB - Antiphospholipid antibodies are associated with recurrent pregnancy loss and thrombosis. Studies suggest that antiphospholipid antibodies may inhibit the production of prostacyclin by vascular tissues. We incubated sera from women with moderate to high levels of antiphospholipid antibodies with primary human umbilical vein endothelial cell cultures. Intact confluent, subconfluent, hydrogen peroxide-damaged, and mechanically damaged endothelial cell monolayers were evaluated for the production of the prostacyclin metabolite 6-keto prostaglandin F1 alpha in the presence of sera that were positive and negative for antiphospholipid antibodies. All sera were assayed for baseline concentrations of 6-keto-prostaglandin F1 alpha before incubation with endothelial monolayers. Additionally, the extent of binding of antiphospholipid antibodies to intact and damaged endothelium was studied by immunofluorescent techniques and enzyme-linked immunosorbent assay. Our results indicate that prostacyclin production is not impaired by sera containing antiphospholipid antibodies, regardless of the condition of the endothelium. Further, we were unable to demonstrate binding of immunoglobulin from sera containing antiphospholipid antibodies to intact or damaged endothelium. However, the baseline concentration of 6-keto-prostaglandin F1 alpha was nearly fourfold higher in sera containing antiphospholipid antibodies. The finding of elevated baseline serum concentrations of prostacyclin metabolite in patients with antiphospholipid antibodies suggests a condition of long-term stimulation or altered metabolism of prostacyclin. PMID- 2109538 TI - Phylogenetic relationships among the Notharctinae of North America. AB - Study of over 1,000 specimens representing all notharctine genera and species leads to the conclusion that current concepts about the relationships of genera within the Notharctinae are incorrect. The following describes the more probable relationships among these genera. 1) Smilodectes and Notharctus are more closely related to each other than either is to any known early Eocene notharctine. Synapomorphies linking these genera include relatively narrow upper and lower molars, a relatively low-crowned P4, and paraconid size reduction on M1-3. 2) Among known Wasatchian notharctines, a clade consisting of Copelemur tutus and Cop. praetutus shares several lower molar synapomorphies with the Notharctus Smilodectes clade, and therefore appears to form the Wasatchian sister group of Bridgerian notharctines. Synapomorphies documenting this relationship include well-developed entoconid notches on P4-M2, an anteriorly placed paraconid on M2, and a long premetacristid on M2. 3) Copelemur and Pelycodus are independently derived from early North American Cantius. Recent suggestions that the European adapine taxa Leptadapis priscus and Microadapis sciureus share special phylogenetic relationships with Smilodectes are rejected. The reduced (or lack of a) paraconid and morphology of the paracristid and other features identified as synapomorphies linking these adapines with Smilodectes are also characteristic of most other adapines as well (e.g., other species of Leptadapis, Adapis, Europolemur, and Anchomomys). Such traits developed independently in Smilodectes, which is clearly a notharctine on the basis of many synapomorphies and thus are not evidence of a close phylogenetic relationship between Smilodectes and L. priscus or M. sciureus. PMID- 2109537 TI - Gamma interferon treatment in vivo provokes accumulation of activated monocytes in the venous circulation of rats. AB - Activated monocytes forming intravascular clumps in the veins of most organs appeared in LEW rats after a 3-day intravenous treatment with recombinant rat gamma interferon. Phenotyping in situ and in cytospot preparations of perfusates revealed that the cells coexpressed the rat monocyte/macrophage antigen ED1 and class II MHC molecules. In addition, most cells reacted with a rat CD11b antibody and weakly expressed determinants detected by the W3/13 and Ox22 reagents. Minor fractions of the activated monocytes were positive for rat CD4 and the Ox2 and ED3 determinants. Cell proliferation was assessed by double staining for bromodeoxyuridine (BrdUrd) incorporation and phenotypic markers. Of the ED 1 positive class II-positive cells, 80% were labeled with BrdUrd after 3 days of combined infusion with gamma interferon. Pulse labeling for 30 minutes revealed 8% BrdUrd-positive intravascular ED 1-positive class II-positive monocytes in situ on day 3 of treatment, which contrasted with almost-absent labeling of this cell population in normal LEW rats. It is concluded that interferon not only promotes activation but also intravascular division of monocytes or their immediate precursors. Interestingly, cells of identical morphology and phenotype were observed in the vasculature of rats during lethal graft-versus-host reactions. Activated monocytes may thus contribute to the pathologic consequences of cytokine treatment and severe systemic immune reactions in vivo. PMID- 2109539 TI - Addition of lithium carbonate to carbamazepine: hematological and thyroid effects. AB - In view of the increasing use of lithium-carbamazepine combination therapy for refractory psychiatric disorders, the authors assessed the clinical laboratory effects of adding lithium to carbamazepine in 23 patients with affective disorders. Lithium produced a robust reversal of carbamazepine-induced leukopenia, increasing WBCs, predominantly neutrophils, to levels significantly above placebo baseline values. The combination produced additive antithyroidal effects, resulting in greater decreases in T4 and free T4 than with carbamazepine alone; the addition of lithium was associated with the emergence of a modestly higher TSH level. The authors discuss clinical and theoretical implications of these findings. PMID- 2109540 TI - Lithium treatment for cocaine abusers with bipolar spectrum disorders. AB - An open trial of lithium carbonate showed little efficacy for 10 cocaine abusers with bipolar spectrum disorders. It may be that the bipolar subgroup of cocaine abusers is heterogeneous and that only a fraction are lithium responsive. PMID- 2109541 TI - Acetazolamide as a control for CO2-induced panic. PMID- 2109542 TI - Use of animals in research on panic disorder. PMID- 2109543 TI - Is it cost-beneficial to screen adolescent males for chlamydia? PMID- 2109544 TI - Screening for Chlamydia trachomatis in adolescent males: a cost-based decision analysis. AB - To evaluate the cost and benefits of screening tests for Chlamydia trachomatis in adolescent males, we developed a decision analysis model and compared the leukocyte esterase urine dipstick test with culture, with direct-smear fluorescent antibody (DFA), and with the option of no screening (no treatment). The leukocyte esterase test has the lowest average cost-per-cure ($51) compared with direct-smear fluorescent antibody ($192) and culture ($414). Compared with the DFA, we estimate that the leukocyte esterase test saves over $9,727 per cohort of 1,000 sexually active adolescent males screened. Sensitivity analyses show the leukocyte esterase test results in a lower cost-per-cure and lower overall costs (per cohort) than culture and direct-smear fluorescent antibody at any prevalence of C. trachomatis infection, and lower overall costs (per cohort) than no screening at prevalences above 21 percent. PMID- 2109545 TI - Community impact of a localized smoking cessation contest. AB - The present study assessed the effectiveness of a localized community contest timed to coincide with a statewide smoking cessation contest. Follow-up interviews were conducted with 218 local contest participants and 198 participants from the statewide contest. Overall cessation impact (participation rate x abstinence) was 0.39 percent for the local contest and 0.09 percent for the statewide contest. Localized community contests offered in conjunction with statewide or national campaigns may represent cost-effective methods of reaching large numbers of smokers. PMID- 2109546 TI - Disease recurrence following liver transplantation. AB - Recurrence of disease following liver transplantation is emerging as a major area of concern. We retrospectively investigated for evidence of recurrent hepatitis B, hepatitis non-A, non-B (NANB), primary biliary cirrhosis (PBC) and malignancy in 106 transplant patients. Recurrence of hepatitis B was diagnosed in 11 of 14 (79%) patients who survived longer than 2 months posttransplant. The first histologic evidence of recurrence occurred at 4 to 64 weeks posttransplant (mean, 22.2 weeks). In two patients, progression to cirrhosis was documented histologically. Recurrence was diagnosed in three patients transplanted for fulminant hepatic necrosis due to hepatitis B. Administration of hepatitis B vaccine and hepatitis B immunoglobulin was ineffective in preventing recurrence. Recurrence of hepatitis NANB was diagnosed in only two of 23 patients transplanted for hepatitis NANB cirrhosis. Evidence of posttransplant hepatitis was also detected in one of 10 patients transplanted for fulminant hepatitic failure presumably caused by hepatitis NANB. Recurrence of PBC was not diagnosed in any of 15 patients, but the length of follow-up was too limited in most patients to allow definite conclusions to be made. Posttransplant antimitochondrial antibodies titers remained elevated in nine of 11 patients tested. Six of 13 patients transplanted for hepatocellular carcinoma (46%) developed recurrent tumor, and five died. The role of preoperative and postoperative chemotherapy is currently undefined. PMID- 2109547 TI - Sodium cromoglycate in the treatment of eosinophilic gastroenteritis. AB - Two patients suffering from eosinophilic gastroenteritis (EG) were treated with sodium cromoglycate (SCG). Before treatment they showed enteric and cutaneous symptoms, such as abdominal pain, nausea, vomiting, diarrhoea and recurrent urticaria and angioedema. The histological findings were a notable amount of eosinophilic infiltration in the lamina propria and gastric glands, a villous shortening and thickening and weak eosinophilic inflammation in the duodenum. The patients were treated with 300 mg SCG, 4 times daily, for 4/5 months. During treatment, the clinical symptoms disappeared and at the end of treatment a reduced inflammation with an almost complete decrease of eosinophilic infiltration was observed. The results provide evidence of SCG efficacy in the treatment of EG and suggest its employment as an alternative to the steroids commonly used in EG. PMID- 2109548 TI - Ferrioxamine and its hexadentate iron-chelating metabolites in human post desferal urine studied by high-performance liquid chromatography and fast atom bombardment mass spectrometry. AB - Three iron-containing fractions were detected by high-performance liquid chromatography (HPLC) on a reverse-phase column in the 24-h urine of two patients with hereditary hemochromatosis following the injection of deferoxamine mesylate (Desferal). These fractions have virtually identical absorption spectra in the visible range, with a broad maximum around 430 nm. Molecular weight determination of these fractions was performed by fast atom bombardment mass spectrometry (FAB MS), which gave intense ion signals for the protonated molecular ions of the intact iron chelates, namely, at m/z 614 for ferrioxamine (FOA; Mr 613), at m/z 629 for metabolite I (FOA-MI; Mr 628), and at m/z 601 for metabolite II (FOA-MII; Mr 600). The molecular weight of FOA-MI is compatible with deamination of the terminal amino function and oxidation of the adjacent carbon atom to a carboxyl group; the molecular weight of FOA-MII is compatible with loss of a C2H4 unit from FOA-MI by beta oxidation. Quantification of iron in post-Desferal urine samples either by atomic absorption spectrometry (AAS) or by HPLC leads to results which are identical within experimental error. In ten subsequent 12-h urine samples of a patient under therapy (subcutaneous infusion of Desferal), the following distribution of urinary iron was found: FOA-MI, 58.4 +/- 4.7% (arithmetic mean +/- SD); FOA, 33.2 +/- 4.9%; FOA-MII, 8.4 +/- 1.7%. Addition of 2 mM ethylenediaminetetraacetic acid (EDTA) to the chromatographic solvents was used as a stability test for FOA and its two metabolites MI and MII.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109549 TI - Partial purification of a thylakoid-bound enzyme using temperature-induced phase partitioning. AB - Triton X-114 was used to partially purify broad bean polyphenol oxidase, a thylakoid membrane-bound enzyme, in latent form, free of phenolic compounds and chlorophylls, with a high recovery rate. The activation of the latent enzyme by detergents or trypsin was 10 times higher than that obtained when the enzyme was purified by other methods used in plant biochemistry, such as acetone powders and ammonium sulfate fractionation. The kinetic parameters of the latent and activated enzyme are also given. PMID- 2109550 TI - The use of acetylated factor X to prevent feedback activation of factor VIII during factor X activation: a tool for kinetic studies. AB - The modification of human factor X by 2-sulfo-N-succinimidyl acetate was investigated and shown to produce a factor X species which, when activated, has no activity toward factor VIII. Acylation of factor X (0.9 microM) was carried out in the presence of 1 mM calcium at different reagent concentrations and pH values at 22 degrees C for time courses up to 1 h. Optimal modification was achieved using 0.3 mM reagent at pH 8.0 for 30 min. The modified zymogen, acetylated factor X, is activated at full rates by factor IXa/VIIIa and by the factor X-activating protein of Russell's viper venom. The activated product, acetylated Xa, has an enhanced amidolytic activity (110%) but has almost no detectable clotting activity (0.1%). More importantly, we have shown that acetylated Xa, in contrast to native Xa, does not activate factor VIII. This allows accurate quantitation of factor VIII activation without complications due to positive feedback reactions. We have demonstrated this in an examination of the activation of factor VIII by factor IXa. PMID- 2109551 TI - Determination of hopanoid levels in bacteria using high-performance liquid chromatography. AB - A reverse-phase HPLC method to detect and quantify levels of hopanoids in bacteria has been developed. Chromophores have been introduced by derivatization and the levels of the C35 hopanoids and their conjugates can be measured in bacterial lipid extracts down to picomole levels. Some structural variations of the complex lipids were detected after derivatization and were easily purified using the same HPLC system. Zymomonas mobilis and Rhodospirillum rubrum extracts were examined using this system and different structural examples of the lipids were detected. The relative levels of the different triterpenes were very dependent on the growth conditions. PMID- 2109552 TI - Use of reference pools to compare the qualitative and quantitative determination of polychlorinated biphenyls by packed and capillary gas chromatography with electron capture detection. Part 1. Serum. AB - Serum for reference pools of in vivo polychlorinated biphenyls (PCBs) was obtained from four goats that had received one dose (100 mg kg-1) of a selected technical Aroclor (AR) (1016, 1242, 1254 or 1260) and were allowed to recover for 30 d. These pools were used to assess the differences in an analytical method that determines and quantifies PCBs using packed-column gas chromatography (PCGC) (quantified on the basis of mean mass percent. data for grouped PCB peaks) and capillary-column gas chromatography (CCGC) (quantified on the basis of percent. composition data for specific congeners). With CCGC, results were statistically significantly different (p less than or equal to 0.0002) from results with PCGC for ARs 1016, 1242 and 1254 but not for AR 1260 (p = 0.23). When comparing these gas chromatographic methods using bovine serum spiked in vitro with the same ARs at 17-25 p.p.b., it was found that the methods were not statistically significantly different for any of the ARs (p = 0.30-0.92). Levels of serum PCB determined by the two methods for 12 persons, divided into two groups according to exposure, were compared using the paired t-test. Group 1 consisted of three persons with dietary and/or environmental exposure; one with dietary and/or environmental exposure in addition to occupational exposure dating back 20 years. Group 2 consisted of eight persons with recent occupational exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109553 TI - Morphometric analysis of thoracic muscles in wildtype and in bithorax Drosophila. AB - The tergotrochanteral (TTM) "jump" muscles in the second (T2) and third (T3) thoracic segments of the fruit fly, Drosophila melanogaster, were analyzed morphologically and morphometrically in wildtype (Canton-S) and bithorax mutants (abx bx3 pbx/Df(3R)P2). In the transformed T3 segments of mutant flies, the TTMs were greatly increased in fiber number (330% of wildtype), length (141%), and volume (460%), thus manifesting both hyperplasia and hypertrophy. In contrast, TTMs in the "untransformed" T2 segments of mutant flies were both hypoplastic and hypotrophic, in that significant decreases in fiber number (93% of wildtype), length (90%), and volume (80%) were observed. Two relationships emerged from analysis of the morphometric data: 1) Although the fiber numbers and volumes of the transformed T3 TTMs in bithorax flies were greatly increased, the total combined volumes of the TTMs in T2 + T3 remained approximately the same in bithorax compared to wildtype flies. 2) The changes in TTM volumes in bithorax flies compared to those in wildtype were proportional to the relative changes in fiber numbers times the relative changes in muscle lengths. These observations suggest that the genes of the bithorax complex influence the number and the length of tubular muscles fibers of the TTMs, but do not significantly affect the mean cross-sectional areas of these fibers. Fibrillar muscle fibers, which are not found at all in T3 segments in wildtype flies, were observed in the transformed T3 segments of bithorax mutants in 11 of 18 cases (61%), but typically as wisps, not in complete muscles. We suggest that, in the T3 segment of the bithorax flies, the relative differences between the massive transformation of tubular TTMs vs. the minimal appearance of fibrillar muscles may be related, in part, to the relative availability of muscle precursors. PMID- 2109554 TI - Bovine T-lymphocyte lines reactive with Brucella abortus. AB - Bovine T-cell lines reactive with Brucella abortus were established by repeated stimulation with B abortus and mitomycin C-treated autologous antigen-presenting cells. Representative results were obtained, using 33 cell lines from 14 cows. Cultures responded to the virulent laboratory strain 2308, the vaccine strain 19, and the rough mutant strain RB51 in thymidine-incorporation assays. The cells in these cultures required antigen-presenting cells for their response to B abortus. Autologous antigen-presenting cells were optimal for most lines tested, although some T-cell lines could respond to B abortus in the presence of some, but not all, allogeneic antigen-presenting cells. The cell lines expressed cell surface markers characteristics of activated bovine T cels. Of the cell lines tested for expression of cluster-determinant (CD) 4 and CD8 cell surface antigens, no cells in any cultures expressed the bovine CD8 equivalent, but all cultures included CD4+ cells in variable amounts. Some cell lines consisted of up to 50% CD2+CD4 CD8- cells. None of the cell lines tested expressed surface immunoglobulin or other bovine B-cell markers. Thus, these long-term cell lines appear to include 2 T-lymphocyte subsets: the helper/inducer subset and a second subset expressing a phenotype similar to major histocompatibility complex-unrestricted cytolytic cells in other species. PMID- 2109555 TI - Differential reactivity of bovine lymphocytes to species of Brucella. AB - The reactivity of bovine lymphocytes to 4 species of Brucella was tested in thymidine-uptake assays, using long-term cultured lymphocytes and freshly obtained blood mononuclear cells. Lymphocytes were taken from cows that had been challenge exposed with a virulent strain of B abortus at midgestation. The cows were classified retrospectively as being naturally resistant or susceptible to brucellosis. Lymphocytes taken from these cows had 3 patterns of reactivity with species of Brucella: pattern 1 was defined by reactivity with 4 species (B abortus, B canis, B suis, and B melitensis); pattern 2 was defined by reactivity with all these species, except B melitensis; pattern 3 was defined by reactivity with B abortus and B canis, but not with B suis or B melitensis. There was a statistically significant correlation between susceptibility to brucellosis and expression of lymphocyte cross-reactivity with B suis (P less than 0.01) and with B melitensis (P less than 0.001). PMID- 2109556 TI - Quantitative and qualitative studies on the major extracellular antigen of Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG. AB - The Mycobacterium tuberculosis antigen 85 is a biologically important antigen. Tuberculosis patients may have strong antibodies against it, and their peripheral blood mononuclear cells respond to it with gamma-interferon production and lymphocyte proliferation. Antigen 85 is actively secreted into the culture medium during culture in vitro and is known to bind human fibronectin. A double-antibody enzyme-linked immunosorbent assay (ELISA) for quantification of antigen 85 is described. A mouse monoclonal antibody, HYT27, was used as capture antibody in the assay. HYT27 was characterized in crossed immunoelectrophoresis and found to bind all three components of the antigen 85 complex. By radioimmunoassay, HYT27 was found to bind equally well to antigens 85A and 85B. In the ELISA assay, a rabbit anti-antigen 85 antiserum was used in the second antibody layer. The specificity of the assay was tested using several different antigen preparations. The purified BCG 85A and 85B components were compared, and there was a 10 times lower sensitivity for antigen 85A due to weaker rabbit antibodies toward this component. The purified components MPT44 and MPT59 from M. tuberculosis H37Rv were compared with the components of BCG and found to correspond to BCG 85A and 85B, respectively. Mycobacterium kansasii and Mycobacterium avium both contained partially identical antigens. Small amounts of antigen 85 were detected in Mycobacterium leprae sonicates. Detecting antigen 85 by sensitive methods may be of great value in the early diagnosis of mycobacterial disease. PMID- 2109557 TI - Eucapnia and hypercapnia in patients with chronic airflow limitation. The role of the upper airway. AB - In this study, we examined two groups of patients with chronic airflow limitation (CAL) separated according to their awake, stable arterial CO2 level. The aim was to identify factors that may contribute to the development of chronic hypercapnic respiratory failure. Patients with obstructive sleep apnea were excluded from the study. Detailed lifetime histories of smoking, alcohol, and snoring were obtained from all patients together with measurements of lung function and of upper airway size. Thirty-three patients with FEV1 less than 1.5 L were studied, of whom 19 were eucapnic and 14 were hypercapnic. Both groups had a similar degree of chronic airflow limitation and similar lung volumes and DLCO. The hypercapnic group had more hypopneas and desaturated more severely during sleep. The greatest differences between the groups were in their alcohol consumptions, snoring histories, and upper airway dimensions. The eucapnic patients were characterized by lower lifetime alcohol intake, minimal snoring, and large upper airway size. In contrast, the hypercapnic patients were characterized by excessive lifetime alcohol consumption, habitual snoring over many years, and a small upper airway size. Our findings suggest that chronic, heavy alcohol use and upper airway dysfunction are important factors in the development of hypercapnic respiratory failure. PMID- 2109558 TI - Reduction of sputum Pseudomonas aeruginosa density by antibiotics improves lung function in cystic fibrosis more than do bronchodilators and chest physiotherapy alone. AB - We evaluated patients with cystic fibrosis (CF) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement. For the first 4 days of study, all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics. During this time, the patients showed significant improvement in mean FVC, FEV1, and maximal midexpiratory flow rate (FEF25-75). In 12 of 13 trials, the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days. In these 12 trials, the patients were stratified by their initial FVC and randomized to receive either parenteral tobramycin and ticarcillin (n = 7) or placebo (n = 5), in addition to continued aerosol and chest physiotherapy. In the remaining trial, the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group. During the next 14 days of therapy, the antibiotic group showed significantly (p less than 0.01) greater reductions in log10 colony-forming units (cfu) of P. aeruginosa per gram of sputum and greater increases in FVC, FEV1, and FEF25-75 than did the placebo group. The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly (p less than 0.001) with the degree of improvement in FVC, FEV1, and FEF25-75.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109559 TI - Relationship of diaphragm glycogen, lactate, and function to respiratory failure. AB - Diaphragmatic function and biochemical changes were studied during respiratory failure induced by incremental inspiratory threshold loading in anesthetized rabbits (1) who were unbound and spontaneously breathing, (2) during lower thoracic and abdominal binding, and (3) while bound and undergoing transvenous phrenic nerve pacing of the diaphragm. There was no evidence of contractile fatigue or alterations in glycogen or lactate concentrations in the diaphragm of unbound spontaneously breathing animals. With thoracoabdominal binding, there was a fall in maximal transdiaphragmatic pressure (Pdimax) and the ratio of diaphragmatic force divided by neural input (Pdi/Edi ratio); there was no change in diaphragm glycogen, but there was a significant rise in lactate. In the bound and phrenic-paced animals Pdimax and Pdi/Edi ratio fell, and there was significant glycogen depletion and lactate accumulation. There was a significant correlation between diaphragm function and the levels of diaphragm glycogen and lactate at the point of respiratory failure. We conclude that (1) respiratory failure induced by incremental inspiratory threshold loading was not associated with either contractile fatigue of the diaphragm or diaphragmatic biochemical changes in unbound spontaneously breathing animals, (2) when mechanisms that preserve diaphragmatic function are circumvented by phrenic pacing and/or thoracoabdominal binding, diaphragm fatigue and biochemical changes occur, and (3) there is a significant relationship between in vivo evidence of contractile fatigue of the diaphragm and diaphragmatic glycogen depletion and lactate accumulation. PMID- 2109560 TI - [Interaction of valproic acid and erythromycin]. PMID- 2109561 TI - [Cholecystic hepatitis and other systemic manifestations caused by Mycoplasma pneumoniae]. PMID- 2109562 TI - [Mucopolysaccharidosis type III A in a girl with atrial septal defect and paroxysmal supraventricular tachycardia]. PMID- 2109564 TI - Tissue plasminogen activator and intracranial hemorrhage. PMID- 2109563 TI - Beta-interferon therapy in patients with poor-prognosis Kaposi sarcoma related to the acquired immunodeficiency syndrome (AIDS). A phase II trial with preliminary evidence of antiviral activity and low incidence of opportunistic infections. AB - STUDY OBJECTIVE: To study the efficacy of high doses of beta-ser-interferon (recombinant human 17-serine beta-interferon) in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. DESIGN: A nonrandomized, controlled trial of two high-dose regimens of beta-ser-interferon administered until tumor progression, toxicity, or an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection occurred. SETTING: An AIDS treatment clinic at a tertiary care center. PATIENTS: A sequential sample of 39 patients with biopsy-proven, AIDS-related Kaposi sarcoma were enrolled during a 2 year period. Thirty-eight patients were evaluable for response. Most patients (35 of 38) had one or more of the following clinical or laboratory predictors for a poor response to interferon therapy: HIV p24 antigenemia, low CD4 cell numbers, elevated beta 2-microglobulin levels, previous opportunistic infections, or previous systemic chemotherapy. INTERVENTIONS: Beta-ser-interferon was self administered subcutaneously at home 5 days per week. The first 21 patients used 90 million IU/d, and the remainder used 180 million IU/d. MEASUREMENTS AND MAIN RESULTS: Six patients (16%) had a major clinical response, and 15 (39%) had stable disease for prolonged periods. Toxicities were minimal; the major toxicity was a skin reaction at the injection site. The HIV p24 antigen level declined more than 50% in 8 of the 19 patients with initial values greater than 50 pg/mL. Antiretroviral activity and antitumor activity were seen only in patients with normal initial beta 2-microglobulin levels. Minimal changes were seen in CD4 and CD8 cell numbers. Only 1 patient had an opportunistic infection while on study, but five other patients developed infections after treatment was discontinued for an incidence of six opportunistic infections in 285 patient-observation months. CONCLUSIONS: The high doses of interferon did not improve the major response rate in patients with poor-prognosis, AIDS-related Kaposi sarcoma. There was, however, a suggestion of antiviral activity in patients with normal beta 2-microglobulin levels and a decrease in the expected incidence of opportunistic infections. PMID- 2109565 TI - Danish approach to the treatment of secretory otitis media. Report of The Danish Consensus Conference. Copenhagen, 1987. PMID- 2109567 TI - Results of a quality assurance exercise for urinary glycosaminoglycan excretion. AB - Urine samples collected from four patients with a mucopolysaccharide storage disease (MPS) and two non-MPS patients were distributed to up to 33 laboratories as a test of their ability to detect abnormal glycosaminoglycan excretion. Seven national reference laboratories made a correct diagnostic assignment to all samples analysed. Qualitative turbidity and spot tests were shown to be unreliable. Failure to identify the excretion pattern occurred when reliance was placed on one-dimensional electrophoresis or thin layer chromatography as the sole method for glycosaminoglycan identification. Two-dimensional electrophoresis appeared to be the method of choice provided that staff had adequate experience in interpretation. Clinically unacceptable delays in analysis were common, with 80% of laboratories taking longer than 10 days to issue a report. PMID- 2109566 TI - An automated assay of glycogen phosphorylase in the direction of phosphorolysis. AB - We have developed a rapid, automated assay for glycogen phosphorylase that measures the degradative reaction. The substrate contains higher concentrations of phosphate and AMP than other methods, and the enzyme is preincubated with the substrate before adding phosphate to start the reaction. These modifications improve the activity and linearity of the assay. The new assay compares favourably with a standard phosphorylase assay in the synthetic direction and is linear to 500 U/L. We have used this assay to measure phosphorylase activity in human tissue samples and muscle biopsy specimens. PMID- 2109568 TI - Syringe injection pressure: a neglected factor in blood PO2 determination. AB - The mean arterial blood PO2 values of 20 patients' samples taken into Sarstedt 2 mL Monovette syringes were found to be initially 0.43 kPa higher and after 15 min storage 0.93 kPa higher than the mean values using Corning 3 mL Blood Gas Kit syringes. The Sarstedt syringe allowed entry of small air bubbles and the plunger was noted to be stiff. We speculated that high injection pressures might increase measured PO2. Using each type of syringe, 20 ITU staff injected saline into a Corning 178 pH/blood analyser linked to a pressure transducer via a three-way connector. Mean injection pressures for Sarstedt and Corning syringes were 17.15 and 6.42 kPa, respectively (P less than 0.005). Following injection at pressures between 2.8 and 26.6 kPa, the mean PO2 of equilibrated saline containing an air bubble was 0.80 kPa higher than the mean value obtained at injection pressures of less than 2.8 kPa. However, with no air bubble the mean PO2 of equilibrated saline was still 0.45 kPa higher when injected at pressures between 2.8 and 26.6 kPa than the mean value obtained with injection pressures of 2.8 kPa. We suggest that for optimal PO2 determinations syringes should not only allow minimal air contamination but also have plungers that reduce injection pressure to a minimum. PMID- 2109569 TI - A case of IgM(kappa) monoclonal gammopathy simulating an IgM-IgG biclonal gammopathy. PMID- 2109570 TI - Inadequacy of urinary urea for the estimation of nitrogen balance during total parenteral nutrition. PMID- 2109571 TI - Mitogen accumulation in von Recklinghausen neurofibromatosis. AB - Most, but not all, patients with von Recklinghausen neurofibromatosis develop tumors (neurofibromas) that contain large numbers of Schwann cells and fibroblasts. To begin to understand the molecular events that contribute to cell proliferation in these benign tumors, we have analyzed extracts of neurofibromas to determine whether they contain mitogens for Schwann cells or fibroblasts, or both. Schwann cell and fibroblast mitogens are present in neurofibroma extracts. All the neurofibromas analyzed contain a Schwann cell mitogen similar to a neuronal cell surface molecule known to stimulate Schwann cell proliferation during normal development; this mitogen also stimulates fibroblast proliferation. Basic fibroblast growth factor is present in 60% of tumors evaluated. Accumulation of mitogenic substances may contribute to the growth of neurofibromas. PMID- 2109572 TI - Eyelid twitching seizures and generalized tonic-clonic convulsions: a syndrome of idiopathic generalized epilepsy. AB - This is a report of two neurologically normal patients who had primary generalized seizures consisting of irregular fluttering or twitching movements of the eyelids accompanied by generalized, rhythmic 9- to 15-Hz electroencephalographic discharges as well as infrequent generalized tonic-clonic seizures. This is a syndrome of idiopathic generalized epilepsy that responds to treatment with valproic acid. PMID- 2109573 TI - Comparison of ofloxacin and ceftriaxone in the treatment of uncomplicated gonorrhea caused by penicillinase-producing and non-penicillinase-producing strains. AB - Eighty-nine patients with uncomplicated gonorrhea, including 31 patients (34.8%) infected with penicillinase-producing strains of Neisseria gonorrhoeae, were treated with oral ofloxacin (single 400-mg dose) or intramuscular ceftriaxone (250-mg dose). All 47 patients who received ofloxacin and 41 of 42 patients who received ceftriaxone were cured. PMID- 2109574 TI - Successful single-dose prophylaxis of Staphylococcus aureus foreign body infections in guinea pigs by fleroxacin. AB - Single-dose administration of fleroxacin was evaluated as a means of preventing foreign body infection due to staphylococci. Tissue cages were implanted into guinea pigs and subsequently infected (100% rate) with 10(2) or more CFU of Staphylococcus aureus Wood 46. When a single dose of 30 mg of fleroxacin or vancomycin per kg of body weight was administered intraperitoneally, bactericidal levels of the antimicrobial agent were found in the tissue cage fluid after 3 h (when guinea pigs were inoculated with S. aureus) and during the next 24 h. Either fleroxacin or vancomycin successfully prevented experimental infection in all tissue cages challenged by 10(2) CFU of S. aureus Wood 46. When tissue cages were challenged with 10(4) CFU of S. aureus Wood 46, however, fleroxacin was more effective than vancomycin (P less than 0.05) in reducing colony counts below the detection limit of 10 CFU/ml in the inflammatory fluid of all tissue cages during the initial 48 h. In contrast to their initially different actions, the effects of the antibiotics were similar after 7 days, mostly because bacterial regrowth occurred more frequently in the fleroxacin-treated than in the vancomycin-treated tissue cages. These data show that experimental infections of subcutaneous tissue cages are a useful model for studying the prophylaxis of foreign body infections with antimicrobial agents. PMID- 2109575 TI - Outer membrane protein D2 catalyzes facilitated diffusion of carbapenems and penems through the outer membrane of Pseudomonas aeruginosa. AB - The outer membrane of imipenem-resistant mutants of Pseudomonas aeruginosa with decreased permeability to imipenem was shown by Western (immuno-) blotting to contain protein D1 and to lack protein D2. Protein D2 was purified and was shown to allow the permeation of imipenem at a rate higher than expected from its molecular weight. Spontaneous imipenem-resistant mutants of P. aeruginosa PAO1 appeared at a frequency of 10(-8) in the laboratory and did not synthesize protein D2. Experiments performed with intact cells carrying plasmid pHN4 containing the gene for L-1 beta-lactamase from Pseudomonas maltophilia showed that this channel could also be used by SM-7338, Sch 33755, and Sch 33440 but apparently not by Sch 34343 or Sch 29482. PMID- 2109576 TI - Renal handling of fleroxacin in rabbits, dogs, and humans. AB - The renal handling of fleroxacin was studied by renal clearance and stop-flow techniques in rabbits and dogs and by analyzing the pharmacokinetics with and without probenecid in humans. In rabbits the excretion ratios (fleroxacin intrinsic renal clearance/glomerular filtration rate) were greater than unity (2.01) without probenecid and were decreased to a value below unity (0.680) with probenecid. In dogs, on the other hand, the excretion ratios were less than unity (0.608 and 0.456) both without and with probenecid, and so were not affected by probenecid. This fact suggested that fleroxacin was excreted into urine by both glomerular filtration and renal tubular secretion in rabbits, but only by glomerular filtration in dogs, accompanied by partial renal tubular reabsorption in both species; these mechanisms were also supported by stop-flow experiments. In humans probenecid treatment induced increases in the elimination half-life and area under the serum concentration-time curve and decreases in apparent serum clearance, renal clearance, and urinary recovery of fleroxacin. The excretion ratio without probenecid was 1.13, which was significantly decreased to 0.750 with probenecid. These results indicated that both renal tubular secretion and reabsorption contributed to renal excretion of fleroxacin in humans. The contribution of tubular secretion was species dependent and was extensive in rabbits, minimal in dogs, and moderate in humans. Renal tubular reabsorption was commonly found in every species. The long elimination half-life of fleroxacin in humans might be explained by its small total serum clearance and small renal clearance, which are attributed to less tubular secretion and more tubular reabsorption. PMID- 2109577 TI - Molecular epidemiology of beta-lactamase-producing enterococci. AB - Plasmids from the first six reported beta-lactamase-producing (Bla+) enterococci were compared for genetic relatedness. Bla+ enterococcal plasmids from strains isolated in Houston, Tex.; Philadelphia, Pa.; Connecticut; and Pittsburgh, Pa., had heterogeneous HaeIII and MspI-ClaI restriction endonuclease digestion patterns. A staphylococcal beta-lactamase probe hybridized to all six Bla+ enterococcal plasmids, but hybridization was detected on different HaeIII and MspI-ClaI fragments of the six plasmids. An enterococcal gentamicin resistance (Gmr) probe hybridized to a common 3.9-kilobase HaeIII fragment from the five Gmr plasmids. The Houston plasmid was cross-hybridized to the other five strains, and moderate to extensive homology was demonstrated. Bla+ enterococcal plasmids from a broad geographic range are heterogeneous with respect to size and restriction endonuclease digestion patterns but contain homologous genetic material, including Bla+ and Gmr determinants. PMID- 2109578 TI - Paradoxical response of Enterococcus faecalis to the bactericidal activity of penicillin is associated with reduced activity of one autolysin. AB - Ten clinical isolates of Enterococcus faecalis were examined for susceptibility to the bactericidal activity of penicillin. Four of these had MBCs of penicillin equal to 2 to 4 x the MIC, and six exhibited a paradoxical response to penicillin, i.e., the bactericidal activity of the antibiotic had a concentration optimum at 2 to 4 x the MIC and decreased significantly at concentrations above this. We found that the paradoxical response to penicillin was an intrinsic and stable property of a strain, but that its phenotypic expression was not homogeneous; only a fraction of the cell population that died at low concentrations was able to survive at high penicillin concentrations. The size of this fraction increased with increasing antibiotic concentration and reached a maximum in the late-log phase of growth. All 10 strains produced a lytic enzyme that was active on Micrococcus luteus heat-killed cells, whereas only some strains lysed E. faecalis heat-killed cells. Strains producing large amounts of the latter enzyme did not show the paradoxical response to penicillin, whereas mutants of these strains that lacked this enzymatic activity paradoxically responded to the antibiotic activity. In addition, from strains that showed paradoxical response to penicillin and produced only the enzyme that was active on M. luteus, it was possible to isolate mutants that were also capable of lysing E. faecalis cells and that were killed with similar efficiency by all concentrations above the MBC. On the basis of these findings, the paradoxical response to penicillin is explained as a property of certain strains of E. faecalis; this property is genetically characterized by alterations in synthesis or activity of one autolysin but phenotypically expressed only by a few cells that are in a particular physiological condition when exposed to high concentrations of antibiotics. PMID- 2109579 TI - Tolerance and efficacy of parenterally administered penicillin-streptomycin and orally administered amoxicillin or penicillin V for prophylaxis of experimentally induced streptococcal endocarditis. AB - A regimen of a single intramuscular dose of penicillin G-streptomycin was compared with regimens of three oral doses of amoxicillin and two oral doses of penicillin V to prevent Streptococcus sanguis endocarditis in rabbits with experimentally induced valvular heart lesions. Challenge doses of 10(4), 10(6), and 10(8) CFU of a strain of S. sanguis highly tolerant to penicillin and amoxicillin were used. The combination of penicillin and streptomycin was the only regimen tested that provided full protection even against the highest inoculum concentration. A single oral dose of penicillin V (36 mg/kg) or amoxicillin (50 mg/kg), two oral doses of penicillin V (36 and 18 mg/kg with a 7 h interval between doses), or six oral doses of amoxicillin (50 mg/kg followed by 8.5 mg/kg at 8-h intervals) protected recipients of the lowest inoculum concentration; protection diminished with increasing inocula. In contrast, administration of two high oral doses of amoxicillin (50 mg/kg) with a 10-h interval between doses provided full protection against challenge doses of 10(4) and 10(6) CFU, preventing endocarditis in 10 (66%) of 15 recipients of 10(8) CFU. All regimens evaluated were highly effective in preventing endocarditis when rabbits were challenged with 10(4) CFU. The combination of penicillin and streptomycin was the best regimen tested. Administration of two high oral doses of amoxicillin (50 mg/kg) with a 10-h interval between doses led to significantly fewer infections when compared with the other oral regimens when rabbits were challenged with 10(6) and 10(8) CFU. PMID- 2109580 TI - Enhanced phagocytosis of encapsulated Escherichia coli strains after exposure to sub-MICs of antibiotics is correlated to changes of the bacterial cell surface. AB - The influence of five antibiotics (netilmicin, ceftriaxone, cefepime, fleroxacin, and ciprofloxacin) on capsular polysaccharide distribution and on opsonophagocytosis by human polymorphonuclear leukocytes of unencapsulated and encapsulated Escherichia coli strains was studied. Unencapsulated E. coli strains were readily opsonized in serum and easily ingested by polymorphonuclear leukocytes, and antibiotics did not further enhance the phagocytosis rates. In contrast, encapsulated bacteria were poorly opsonized in human serum, and phagocytosis was enhanced after overnight exposure to 0.5x the MICs of the antibiotics, with the exception of cefepime. Incubation of unencapsulated as well as encapsulated bacteria in complement-inactivated serum markedly reduced the bacterial uptake by polymorphonuclear leukocytes regardless of the presence of antibiotics. Slide agglutination assays, performed either with a monoclonal antibody for capsular polysaccharide or with an antiserum raised against the stable unencapsulated mutant E. coli O7:K-, showed reduction but not lack of the capsular polysaccharide of encapsulated E. coli O7:K1, and better exposure of subcapsular epitopes, after incubation with 0.5x the MICs of antibiotics. Flow cytometric analysis of encapsulated E. coli exposed to netilmicin, ciprofloxacin, and fleroxacin revealed that the reduction in capsular material was homogeneous among the bacterial population. Treatment with cefepime and ceftriaxone induced two populations of bacteria that differed in the amount of K antigen present. These results indicate that sub-MICs of netilmicin, ceftriaxone, fleroxacin, and ciprofloxacin influenced complement-mediated opsonization, probably due to changes in the capsular polysaccharide structure. PMID- 2109581 TI - Outer membrane permeability and beta-lactamase stability of dipolar ionic cephalosporins containing methoxyimino substituents. AB - Some enteric bacteria, such as Enterobacter cloacae, can develop high-level resistance to broad-spectrum cephalosporins by overproducing their chromosomally encoded type I beta-lactamases. This is because these agents are hydrolyzed rapidly at pharmacologically relevant, low (0.1 to 1 microM), concentrations, owing to their high affinity for type I enzymes. In contrast, the more recently developed cephalosporins, with quaternary-nitrogen-containing substituents at the 3 position, show increased efficacy against beta-lactamase-overproducing strains and, indeed, have a much lower affinity for type I enzymes. However, the possible contribution of an improved outer membrane permeability in their increased efficacy has not been studied. We found by proteoliposome swelling assays that cefepime, cefpirome, and E-1040 all penetrated the porin channels of Escherichia coli and E. cloacae much more rapidly than did ceftazidime and at least as rapidly as did cefotaxime. Considering that the influx of anionic compounds such as cefotaxime and ceftazidime will be further retarded in intact cells, owing to the Donnan potential, we expect that the newer compounds will penetrate intact cells 2 to 10 times more rapidly than will cefotaxime and ceftazidime. The kinetic parameters of hydrolysis of these agents by E. cloacae beta-lactamase showed that at 0.1 microM, they were hydrolyzed much more slowly than was cefotaxime and at about the same rate as or a lower rate than was ceftazidime. The combination of these two effects explains nearly quantitatively why these newer agents are more effective against some of the beta-lactamase-overproducing gram-negative bacteria. PMID- 2109582 TI - In vitro investigation of BK-218, a new oral and parenteral cephalosporin. AB - The antibacterial activity of BK-218 was similar to that of cefamandole when it was tested against several laboratory strains. The inhibiting effect of BK-218 was greater than that of cephalexin and cefoxitin on penicillin-binding proteins of Escherichia coli HB101. This result was in close correlation with the relative inhibition of radiolabeled glucosamine incorporation (greatest with BK-218) and with the lytic effect (most intensive with BK-218). BK-218 proved to be a good inhibitor for all five of the beta-lactamases that were investigated, although two enzymes (Enterobacter cloacae P99 and Pseudomonas aeruginosa Cilote) hydrolyzed it to some extent. PMID- 2109583 TI - In vitro activity of cefpodoxime proxetil (U-76,252; CS-807) against Neisseria gonorrhoeae. AB - Cefpodoxime proxetil is an oral cephalosporin antibiotic. The in vitro activities of cefpodoxime (the active metabolite of cefpodoxime proxetil), ceftriaxone, and cefuroxime against both antibiotic-susceptible and antibiotic-resistant clinical isolates of Neisseria gonorrhoeae were determined. Cefpodoxime inhibited all penicillin-susceptible strains and penicillinase-producing strains at less than or equal to 0.015 microgram/ml; chromosomally resistant strains were inhibited by cefpodoxime at less than or equal to 0.125 microgram/ml. PMID- 2109584 TI - Glucose metabolism and the channeling of glycolytic intermediates in permeabilized L-929 cells. AB - L-929 cells (mouse fibroblasts) permeabilized with dextran sulfate (DSP cells) carry out vigorous and linear rates of glycolysis when supplied with a suitable incubation medium. Glycolysis in DSP cells is pH dependent, being strongly inhibited at pH 6.5. Compared to their nonpermeabilized counterparts, DSP cells exhibit faster glycolytic rates, but tend to convert a smaller proportion of the glucose utilized to lactate. [14C]Glucose is converted to lactate by DSP cells without dilution from endogenous substrates. When exogenous 12C-labeled glycolytic intermediates (12C-I) are added to glycolyzing DSP cells the [14C]lactate produced from [14C]glucose is diluted to varying extents, depending on the intermediate. However, the extent of that dilution (reduced specific activity) is not that expected from the complete mixing of exogenous 12C-I with their corresponding 14C-labeled intermediates coming from [14C]-glucose. DSP cells also respire and convert glucose to CO2. The amount of 14CO2 produced from [14C]glucose is also reduced by addition of most 12C-I, an interesting exception being pyruvate, which had no measurable effect on 14CO2 production and caused only a modest stimulation of respiration in glycolyzing DSP cells. These results suggest that channeling, or some other form of coupling, takes place between the glycolytic production of pyruvate and its further oxidation. These observations confirm previously published data and add further support to the proposition that channeling of glycolytic intermediates occurs in DSP cells but is of the "leaky" type. Although abundant evidence in the literature indicates that various glycolytic enzymes associate with F-actin, as well as other elements of the cytomatrix, we observed no effect of cytochalasin D on lactate production even at very high concentrations of this compound. Our results are compared with those from other laboratories and discussed in the context of metabolic organization. PMID- 2109585 TI - Thyroid dysfunction in adults over age 55 years. A study in an urban US community. AB - The prevalence of thyroid dysfunction was determined in a healthy urban population over the age of 55 years. A highly sensitive serum thyrotropin assay was used initially to screen 968 subjects. Elevated values (greater than 6 mU/L) were found in 7.3%, while suppressed values (less than 0.1 mU/L) were present in 2.5% subjects. Protirelin stimulation testing demonstrated exaggerated responses in 95% of the subjects with elevated thyrotropin levels and subnormal responses in 81% of the subjects with suppressed thyrotropin levels. Thyroid dysfunction, as defined by abnormalities of both serum thyrotropin level and protirelin response, was calculated to be present in 8.9% of the population. The prevalence was greater in whites (vs blacks), in women, and in subjects older than 75 years as compared with the 55- to 64-year age group. Hypothyroidism was calculated to be present in 6.9% subjects. Despite an increased prevalence of thyroid autoantibodies in these subjects, only 8.5% of them had subnormal serum thyroxine concentrations. Hyperthyroidism was calculated to be present in 2.0% of the population, two thirds of whom were taking thyroid hormone preparations. These results suggest a significant prevalence of thyroid dysfunction in the elderly, with important sex and racial differences. PMID- 2109586 TI - Tube feeding in elderly patients. PMID- 2109587 TI - Acute voluntary life-threatening carbonate lithium poisoning. PMID- 2109588 TI - Prospective payment for rehabilitation: effects on hospital readmission, home care, and placement. AB - Suspected benefits of a prospective payment system (PPS) in which hospitals are paid by diagnosis-related groups (DRGs) are that hospital lengths of stay and costs may be reduced. The US Department of Veterans Affairs is one of the first agencies to adopt PPS funding for rehabilitation; this early adoption of PPS provides a unique opportunity to test for both beneficial and adverse outcomes. This study compared hospital stay, readmission rate, and incidence of nursing home placement before and after introduction of PPS on a 22-bed rehabilitation service. Hospital stay decreased from 29.3 days to 26.4 days, but 64% more patients were discharged to nursing homes. Findings suggest that PPS may overlook home care in favor of placement, which neutralizes the cost benefits of the proposed reimbursement system. Further research on the effects of PPS is needed to determine (1) impact on clinical aspects of rehabilitation and (2) whether other funding mechanisms are more appropriate. PMID- 2109589 TI - Localization of the 34 kDa polyhedron envelope protein in Spodoptera frugiperda cells infected with Autographa californica nuclear polyhedrosis virus. AB - Using immuno-electron microscopy the 34 kDa polyhedron envelope (PE) phosphoprotein (pp 34) was localized in cells infected with Autographa californica multiple-nucleocapsid nuclear polyhedrosis virus (AcMNPV). In wild type AcMNPV-infected cells this protein was found associated with electron-dense "spacers" and the polyhedron envelopes demonstrating their structural relationship. In these cells pp 34 was also found associated with fibrillar structures present in the nucleus and cytoplasm of infected cells. However, when cells were infected with an AcMNPV mutant with an inactivated pp 34 gene, antiserum against pp 34 still localized in fibrillar structures. In cells infected with AcMNPV mutants lacking p 10, and thus devoid of fibrillar structures, pp 34 localized normally with both electron-dense "spacers" and polyhedron envelopes. These data confirm that fibrillar structures are not essential for the morphogenesis of polyhedron envelopes and demonstrate that the association of anti pp 34 serum with these structures is specific but fortuitous. PMID- 2109590 TI - A CD 4: immunoglobulin fusion protein with antiviral effects against HIV. AB - Antibody-like molecules consisting of the human CD 4 extracellular domain fused to human IgG1 heavy chain constant regions were genetically constructed and expressed in a BHK cell stable transfectant. Purified chimeric antibodies bound to HIV particles as it was shown by immuno electron microscopy, inhibited fusions of HIV-1-infected cells with uninfected cells, neutralized HIV-1, and were able to inhibit the spread of a cellular HIV-1 infection in CD 4+ cells. Plaque reduction assays with CD 4(+)-transfected Hela-cells showed a comparable inhibition of HIV-1 and HIV-2. Inhibitory functions were enhanced in the presence of complement. HIV-1- and HIV-2-infected CD 4+ cells were efficiently lysed by a slow, complement-dependent mechanism, whereas uninfected CD 4+ cells and HLA-DR+ cells were not affected. PMID- 2109592 TI - Archibald Watson lecture. Impact of technology on surgery. PMID- 2109591 TI - Immunosuppressive effect of misoprostol: a new synthetic prostaglandin E1 analogue. AB - Prostaglandins are reported to play an important regulatory role in cell-mediated immunity. The immunosuppressive properties of a new synthetic oral prostaglandin E1 analogue, misoprostol, were studied in vivo in a rat heterotopic cardiac allograft model, and in vitro in mixed lymphocyte reaction. The results show that parenteral misoprostol, alone or in combination with low dose cyclosporin immunosuppressive therapy, significantly prolonged cardiac allograft survival compared with appropriate controls. Oral misoprostol alone in this model did not allow for measurable cardiac allograft prolongation. In vitro misoprostol demonstrated significant dose-response inhibition of the mixed lymphocyte culture assay. It is concluded that new prostaglandin E1 analogues with oral bioavailability may have important applications to clinical transplantation in man, and may be cyclosporin sparing. PMID- 2109593 TI - Inhibition of tumor promotion by DL-alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase. AB - Knowledge of the mechanisms of carcinogenesis is helpful for planning strategies and in the rational choice of agents for cancer prevention. There is a great potential for intervention at the promotion step of human carcinogenesis. ODC induction is associated with the promotion stage of carcinogenesis. Consequently, DFMO may be a useful drug for cancer prevention in humans. Long-term medication with higher doses (9 gm/m2/da) of DFMO has resulted in several toxic side effects, such as thrombocytopenia and reversible ototoxicity. However, doses of DFMO (less than 1 gm/m2/da), selected by our in vitro human skin punch biopsy assay (16, 47), may be given for a longer period without appreciable toxicity and should be evaluated in human cancer prevention trials. PMID- 2109594 TI - Chemoprevention of mammary cancer by retinoids. PMID- 2109595 TI - Suppression of tumor promotion by inhibitors of poly(ADP)ribose formation. AB - Tumor promoters, such as phorbol esters or hormones, cause many biological effects which may contribute to the expression of cancer. The mechanism of cancer expression may have a common theme. One method of learning about this common mechanism is the identification of chemicals that interfere with tumor development. That there is actually a common theme between very different substances, such as inflammatory skin tumor promoters and estradiol causing breast cancer, was shown by the fact that both skin and breast cancers are suppressed by the same agents, e.g., protease inhibitors and retinoids. In addition to skin and breast, protease inhibitors suppress colon, bladder, and liver cancers. The substances that crossed over in suppressing many varieties of cancer were found to inhibit oxygen radical formation by tumor promoter-activated neutrophils and ras oncogene expression in NIH 3T3 cells. Poly(ADP)ribose polymerase (PADPR polymerase) may serve as the connecting link between oxygen radicals that cause its activation and oncogene expression. PADPR polymerase is inhibited by retinoids, antioxidants, and some protease inhibitors. Benzamide, an inhibitor of PADPR polymerase, is also a chymotrypsin inhibitor which suppresses oxygen radical formation by tumor promoter-activated neutrophils. The inhibition of PADPR polymerase causes the expulsion of some oncogenes from NIH 3T3 cells at definite times after oncogene transfection. Further work is required to find what are the contributions of PADPR polymerase to tumor promotion and of its inhibitors to suppression of oncogene expression. PMID- 2109596 TI - Inhibition of the genotoxicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P 2) in Drosophila by chlorophyll. PMID- 2109597 TI - Tumor dose-response studies with aflatoxin B1 and the ambivalent modulator indole 3-carbinol: inhibitory versus promotional potency. AB - Indole-3-carbinol (I3C), a natural compound from cruciferous vegetables, inhibits aflatoxin B1 (AFB1) carcinogenesis in trout when administered prior to and during carcinogen exposure, but also promotes it in the same species when given after AFB1 initiation. To provide quantitative potency information for these opposing activities, detailed tumor dose-response studies were performed with AFB1 (10-400 ppb) and I3C (0-4,000 ppm). In a plot of (logit) percent tumor response vs log AFB1 exposure, the results generated a series of parallel AFB1 dose-response curves. Increasing I3C doses displaced these curves, respectively, toward higher and lower AFB1 doses in the inhibition and promotion studies. Similar potencies were observed over the dose range 0-1,500 ppm I3C; the 50% promotion and inhibition (P50 and I50) values were 1,000 vs 1,400 ppm I3C, respectively. Differences in the protocols used in the two studies suggest that the inhibitory activity of I3C is more likely to supersede promotion under human exposure conditions. PMID- 2109598 TI - Reversion of transformed NIH 3T3 cells to flat cells by inhibitors of poly(ADP ribose) polymerase. PMID- 2109599 TI - Role of a nonsteroidal anti-inflammatory agent, ibuprofen, in coronary revascularization after acute myocardial infarction. AB - The efficacy of using a nonsteroidal anti-inflammatory agent such as ibuprofen for the salvage of ischemic and reperfused myocardium was investigated by examining its ability to improve global and regional functions as well as to preserve high-energy phosphate compounds and inhibit creatine kinase release from an isolated in-situ pig heart subjected to 1 h of normothermic regional ischemia followed by 1 h of global hypothermic arrest and 1 h of normothermic reperfusion. Preperfusion of the heart for 15 min prior to ischemic insult with 50 microM ibuprofen failed to mitigate the myocardial reperfusion injury. Ibuprofen, however, functioned as an anti-inflammatory agent, as judged by its ability to inhibit the influx of indium-111-labeled polymorphonuclear leukocytes and chromium-51 (51Cr)-labeled platelets into the ischemic and reperfused heart. It also blocked the cyclooxygenase pathway, as evidenced by the significant reduction of 6-keto-prostaglandin F1 alpha and thromboxane B2 concentrations in the perfusate. Inhibition of cyclooxygenase resulted in increased accumulation of nonesterified fatty acids, particularly arachidonic acid, in the heart. These results suggest that although ibuprofen can inhibit polymorphonuclear leukocyte and platelet influx into the ischemic and reperfused heart, it causes further damage to the already ischemic heart by reducing prostacyclin concentration and increasing free fatty acids in the heart. PMID- 2109600 TI - Calditol tetraether lipids of the archaebacterium Sulfolobus solfataricus. Biosynthetic studies. AB - Lipids from the archaebacterium Sulfolobus solfataricus are based on 72-membered macrocyclic tetraethers made up from two C40 diol units differently cyclized and either two glycerol moieties or one glycerol moiety and a unique branched-chain nonitol named calditol (glycerodialkylnonitol tetraethers, GDNTs). To elucidate the biosynthesis of calditol and related tetraethers, labelled precursors, [U 14C,1(3)-3H]glycerol, [U-14C,2-3H]glycerol, D-[1-14C,6-3H]glucose, D-[6-14C,1 3H]glucose, D-[1-14C,2-3H]glucose, D-[1-14C,6-3H]fructose and D-[1-14C]galactose, were fed to S. solfataricus. Without regard to stereochemistry or phosphorylation, incorporation experiments provided evidence that the biosynthesis of calditol occurs via an aldolic condensation between dihydroxyacetone and fructose, through a 2-oxo derivative of calditol as an intermediate. The latter is in turn reduced and then alkylated to yield the GDNTs. The biogenetic origins of both glycerol and C40 isoprenoid moieties of GDNTs are also discussed. PMID- 2109601 TI - A role for calcium and protein kinase C in agonist-stimulated adhesion of human neutrophils. AB - Stimulated adherence of human neutrophils to plastic and changes in cytosolic free Ca2+ concn. [( Ca2+]i) were measured in the same cell preparations. [Ca2+]i activation curves were constructed to compare the relation between [Ca2+]i and adhesion in response to ionomycin and formylmethionyl-leucyl-phenylalanine (FMLP). This showed that FMLP-stimulated adhesion required less increase in [Ca2+]i than did ionomycin's effect, a result suggesting that an additional stimulatory component might be involved in the response to FMLP. Protein kinase C activation was a possibility, and activation of protein kinase C with a phorbol ester (PMA) was found to stimulate adhesion with no change in [Ca2+]i. A low concentration of PMA was found to synergize with ionomycin to stimulate a greater adhesion response than with each alone, and the [Ca2+]i-activation curve for ionomycin in the presence of PMA was shifted towards that for FMLP. Thus, synergy between [Ca2+]i and protein kinase C (each of which is sufficient alone) probably explains the stimulatory effects of FMLP on adhesion of neutrophils. PMID- 2109602 TI - Shedding of hyaluronate synthase from streptococci. AB - Hyaluronate synthase was shed into the culture medium from growing streptococci (group C) together with nascent hyaluronate. The mechanism of solubilization was analysed using isolated protoplast membranes. Solubilization increased when membranes were suspended in larger volumes, but it was temperature-independent and was not inhibited by protease inhibitors. Increased hyaluronate chain length enhanced solubilization. The soluble synthase could re-integrate into Streptococcal membranes in a saturable manner. The soluble synthase behaved like an integral membrane protein, although it was not integrated into phospholipid vesicles. In sucrose velocity centrifugation the synthase had a higher sedimentation rate in detergent-free solution, indicating that it existed in an aggregated state. PMID- 2109603 TI - Structure of the lysosomal neuraminidase-beta-galactosidase-carboxypeptidase multienzymic complex. AB - Lysosomal neuraminidase (sialidase; EC 3.2.1.18) and beta-galactosidase (EC 3.2.1.23), together with a carboxypeptidase, the so-called 'protective protein', were co-purified from the human placenta by affinity chromatography on a concanavalin A-Sepharose column followed by a thiogalactoside-agarose affinity column for beta-galactosidase. Analysis of the purified material by gel filtration h.p.l.c. revealed three distinct molecular forms, all with high beta galactosidase specific activity, but only the largest one expressed neuraminidase activity. Rechromatography of each individual species separately indicated that all three are in fact part of an equilibrium system (the neuraminidase-beta galactosidase-carboxypeptidase complex or NGC-complex) and that these species undergo slow conversion into one another through dissociation and association of protomeric components. Each species was sufficiently stable for the determination of their hydrodynamic properties by gel-filtration h.p.l.c. and sedimentation velocity. The largest species had an apparent sedimentation coefficient S20.w, of 18.8 S and a Stokes' radius of 8.5 nm, giving a molecular mass of 679 kDa and a fractional ratio, f/f min, of 1.47. The latter value indicates that the macromolecule is asymmetric or highly hydrated. This large species is composed of four types of polypeptide chains of molecular mass 66 kDa (neuraminidase), 63 kDa (beta-galactosidase), 32 kDa and 20 kDa (carboxypeptidase heterodimer). The 32 kDa and 20 kDa protomers are linked together by a disulphide bridge. Glycopeptidase F digestion of the NGC-complex transformed the diffuse 66-63 kDa band on the SDS gel into two close but sharp bands at 58 and 56 kDa. The two smaller species which were separated on the h.p.l.c. column correspond to tetrameric and dimeric forms of the 66-63 kDa protomers and express exclusively beta-galactosidase activity. Treatment of the NGC-complex with increasing concentrations of guanidinium hydrochloride up to 1.5 M also resulted in dissociation of the complex into the same smaller species mentioned above plus two protomers of molecular mass around 60 and 50 kDa. A model of the largest molecular species as a hexamer of the 66-63 kDa protomers associated to five carboxypeptidase heterodimers (32 kDa and 20 kDa) is proposed PMID- 2109605 TI - Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA. AB - The antiproliferative action of human interferon (HuIFN)-gamma on human cells and the inhibition of intracellular pathogens, e.g. Toxoplasma gondii and Chlamydia psittaci, is at least in part due to an induction of indoleamine 2,3-dioxygenase (IDO) enzyme which degrades tryptophan, an essential amino acid. A cDNA clone (called C42) was isolated from a cDNA library made from poly(A)+ RNA obtained from HuIFN-gamma-treated human fibroblasts. Its nucleotide sequence revealed an open reading frame coding for a polypeptide of 403 amino acids, but no homology with any known gene in GenBank database was found. Evidence was obtained indicating that this cDNA codes for IDO: (i) Hybrid selected C42 specific poly(A)+ RNA from IFN-gamma-treated human cells coded for a polypeptide in vitro of approximately 42 kD (reported size of IDO, approximately 40 kD) which was immunoprecipitated by monoclonal anti-IDO antibody but not by a control antibody; and (ii) transfection of human fibroblasts with an expression plasmid containing C42 cDNA transcribed from chicken beta-actin promoter led to constitutive expression of C42 specific RNA as well as IDO activity. This cDNA clone will be useful in studying the role of IDO in the biological effects of IFN-gamma, and the regulation of IDO gene by IFN-gamma. PMID- 2109604 TI - Oral administration of vanadate to streptozotocin-diabetic rats restores the glucose-induced activation of liver glycogen synthase. AB - Isolated hepatocytes from streptozotocin-diabetic rats failed to respond to a glucose load with an activation of glycogen synthase. This lesion was associated with severely decreased activities of glycogen-synthase phosphatase and of glucokinase. All these defects were abolished after consumption for 13-18 days of drinking water containing Na3VO4 (0.7 mg/ml), and they were partially restored after 3.5 days, when the blood glucose concentration was already normalized. In all conditions the maximal extent of activation of glycogen synthase in cells closely parallelled the activity of glycogen-synthase phosphatase. PMID- 2109606 TI - A stage in glycolysis controls the metabolic adjustments of vertebrate rod photoreceptors upon illumination. AB - The factors affecting the metabolic adjustments of toad rod photoreceptors were studied by monitoring the oxygen utilization of excised retinas and by measuring rod outer segment ATP and GTP concentrations. Respiratory adjustments upon illumination were observed when glucose or fructose was provided in the perfusate, but not when a glycolytic inhibitor was added to the perfusate containing glucose and pyruvate, or when a substrate beyond glycolysis or from a later stage of glycolysis was substituted for glucose. The amplitudes of the respiratory adjustments to illumination were dependent on the concentration of glucose in the perfusate. The ATP and GTP concentration changes were dependent on respiratory adjustments, including glycolytic effects, and on the levels of illumination. The data suggest a control point within glycolysis for light induced adjustments of respiration, possibly at phosphofructokinase. PMID- 2109607 TI - Particles of photosystem 2 contain plantacyanin. AB - PS2 particles prepared from chloroplasts of three plant species were shown to contain the basic blue copper protein, plantacyanin, which may be extracted from the particles by concentrated saline solutions containing Triton X-100. Antibodies to plantacyanin were found to inhibit the photosynthetic oxygen evolution performed by the particles. Thus, evidences were obtained for participation of this protein in the oxygen-evolving activity of PS2 particles. PMID- 2109608 TI - Molecular analysis of alpha ecdysone induced 16S complexes in Drosophila Schneider's S3 cells. AB - The molecular organization of alpha ecdysone induced small heat shock proteins (small hsps) in Schneider's S3 tissue culture cells was analysed. Sucrose gradient centrifugation of cytoplasmic extracts and nondenaturing gel electrophoresis shows that hormone induced small hsps form 16S particles which differ in the relative molar ratios of the small hsps composing the 16S particles. The 16S particles possess a buoyant density in Cs2SO4 of rho = 1.34 g/cm3 which is indicative of RNP complexes with an RNA:protein ratio of 1:4. The RNA component of the 16S particles was identified by cDNA cloning using a cDNA library established from alpha ecdysone induced pupal 16S material. Northern hybridization using the 16S RNP specific partial cDNA clone Ec3 identifies a single alpha ecdysone inducible 300 nt RNA species. Our data suggest that the small hsps may unfold their so far unresolved function in form of RNP complexes. PMID- 2109609 TI - Stimulation of platelet-derived growth factor-induced DNA synthesis by angiotensin II in rabbit vascular smooth muscle cells. AB - In cultured rabbit vascular smooth muscle cells (VSMCs), angiotensin II by itself had little mitogenic effect even in the presence of cell-free plasma-derived serum (PDS), but markedly stimulated the platelet-derived growth factor (PDGF) induced DNA synthesis in the presence of PDS. The maximal extent of DNA synthesis induced by PDGF plus angiotensin II was about twice that induced by PDGF alone. The stimulatory effect of angiotensin II was dose-dependent with the maximal response seen at 1 microM and was inhibited by the specific angiotensin II receptor antagonist, [Sar1, Ile8]angiotensin II. In VSMCs, both PDGF and angiotensin II induced expression of the c-fos gene in dose-dependent manners. In contrast to the synergistic effect of angiotensin II and PDGF on DNA synthesis, they induced expression of the c-fos gene in an additive manner. These results suggest that angiotensin II may act as a growth regulator for VSMCs in addition to acting as a vasoconstrictor. PMID- 2109610 TI - Improved resolution of the initial fast phase of heavy sarcoplasmic reticulum Ca2+ uptake by Ca2+:antipyrylazo III dual-wavelength spectroscopy. AB - The effect of ATP upon difference absorbance due to Ca2+ and Mg2+ complexation with the metallochromic dye, Antipyrylazo III (AP III), was investigated. At divalent cation concentrations appropriate for Sarcoplasmic Reticulum Ca2+ transport, wavelengths (greater than 670 nm) were found whereupon the addition of up to 1mM nucleotide did not alter divalent cation:AP III difference absorbance. At these sample wavelengths an initial rapid uptake of Ca2+ by Heavy SR (HSR) was clearly resolved by dual wavelength spectroscopy of Ca2+:dye difference absorbance. Elimination of ATP interference of Ca2+:AP III absorbance by Mg2+ elevation (3-10mM) was shown to be an inappropriate general strategy for AP III spectroscopic studies of HSR Ca2+ transport due to Mg2+ inhibition of ryanodine receptor mediated Ca2+ release. PMID- 2109611 TI - Characterization of multiple active forms of the NADPH dehydrogenase component of the oxidase complex from rabbit peritoneal neutrophils by photolabeling with an arylazido derivative of NADP+. AB - A NADPH cytochrome c oxidoreductase purified from membranes of rabbit peritoneal neutrophil was shown to behave as the NADPH dehydrogenase component of the O2- generating oxidase complex. A photoactivable derivative of NADP+, azido nitrophenyl-gamma-aminobutyryl NADP+ (NAP4-NADP+), was synthesized in its labeled [3H] form and used to photolabel the NADPH cytochrome c reductase at different stages of the purification procedure. Control assays performed in dim light indicated that the reduced form of NADP4-NADP+ generated by reduction with glucose-6-phosphate and glucose-6-phosphate dehydrogenase was oxidized at virtually the same rate as NADPH. Upon photoirradiation of the purified reductase in the presence of [3H]NAP4-NADP+ and subsequent separation of the photolabeled species by sodium dodecyl sulfate polyacrylamide gel electrophoresis, radioactivity was found to be present predominantly in a protein band with a molecular mass of 77-kDa and accessorily in bands of 67-kDa and 57-kDa. Evidence is provided that the 67-kDa and 57-kDa proteins arose from the 77-kDa protein by proteolysis. Despite removal of part of the sequence, the proteolyzed proteins were still active in catalyzing electron transport from NADPH to cytochrome c and in binding the photoactivable derivative of NADP+. PMID- 2109612 TI - A unique mRNA species for the alpha subunit of Gs is present in rat haploid germ cells. AB - The 1.9 kb mRNA encoding the alpha subunit of Gs observed in the somatic cells of the rat testis was not seen in the germ cells (pachytene spermatocytes and round spermatids) as revealed by Northern blot analysis. Interestingly, the cDNA probe for Gs alpha detected a mRNA of shorter chain length (0.9 kb) exclusively in the haploid germ cells (round and elongated spermatids). However, no ADP ribosylated protein was detected in membranes from germ cells after cholera toxin treatment. The 0.9 kb transcript may represent a haploid germ cell-specific variant of Gs alpha, which is functionally different from the stimulatory component of the adenylate cyclase system. PMID- 2109613 TI - Analysis of improvement in individual rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs, based on the findings in patients treated with placebo. The Cooperative Systematic Studies of Rheumatic Diseases Group. AB - A composite index for estimating improvement in individual rheumatoid arthritis (RA) patients during trials of slow-acting, disease-modifying antirheumatic drugs (DMARDs) was developed by analyzing the responses of 130 placebo-treated participants in Cooperative Systematic Studies of Rheumatic Diseases studies. If responses in 4 of 6 selected measures were required for improvement (by greater than or equal to 20% for morning stiffness, Westergren erythrocyte sedimentation rate, joint pain/tenderness score, and joint swelling score, and by greater than or equal to 2 grades on a 5-grade scale, or from grade 2 to grade 1 for patient's and physician's overall assessments of current disease severity), few placebo treated patients qualified as improved, whereas significantly more DMARD-treated patients demonstrated improvement. The proposed index appears to be useful in estimating the probability that an RA patient will improve if taking a placebo during a DMARD trial, and may be a useful tool for analysis of DMARD studies. PMID- 2109614 TI - Characteristics of high-titer IgG antiphospholipid antibody in systemic lupus erythematosus patients with and without fetal death. AB - Although high-titer IgG antiphospholipid antibody (aPL) is a predictor of mid pregnancy fetal death in women with systemic lupus erythematosus (SLE), some SLE patients with high-titer aPL carry pregnancies normally, and to term. To determine potential antibody differences between IgG aPL-positive women with and without fetal death, we studied aPL isotype, subclass, anticoagulant activity, phospholipid specificity, and antibody avidity in selected sera from pregnant SLE patients with high-titer IgG aPL. For controls, we selected sera from pregnant SLE patients who had negative results on tests for IgG aPL (with and without fetal loss). None of the specified antibody characteristics distinguished between the aPL-positive patient groups, nor were other specificities defined in IgG aPL negative sera from women with fetal death. Although high-titer aPL is a good predictor of fetal death, currently known characteristics, other than a high titer of aPL, do not identify which women will experience this complication. PMID- 2109615 TI - Sequence of I-E genes from autoimmune New Zealand white mice. AB - Autoimmune New Zealand white (NZW) mice contribute to (New Zealand black x New Zealand white)F1 mice 1 or more major histocompatibility complex-linked genes that strongly correlate with susceptibility to murine lupus. The NZW class II major histocompatibility complex genes, I-E alpha and I-E beta, were cloned and sequenced and found to differ from normal B10.PL (H-2u) mice by 3 amino acids in the first domain of the I-E beta subunit. Of these differences, the arginine at position 72 of NZW mice could be an important disease determinant since it lies in a predicted antigen-binding cleft. PMID- 2109616 TI - Reduced benzo-a-pyrene activation potential in lymphocytes from chronic alcoholics. AB - The effect of chronic ethanol consumption on the cellular metabolism of benzo-a pyrene (BaP) is investigated in human peripheral lymphocytes obtained from 6 proven alcoholic addicts and 5 healthy donors. Lymphocytes convert BaP to dihydrodiols, diol-epoxides, phenols, quinone derivatives and polyhydroxylated forms. Sulfate, glucuronide and glutathione conjugates are also detected. The average production of metabolites is much lower in lymphocytes of alcoholics and a net global decrease of "active" metabolite production, i.e., diols and BPDE, is also observed. In contrast, conjugated metabolites are formed in increased amounts. The data indicate that the metabolism of BaP in lymphocytes from chronic alcoholics is characterized essentially by a lowered rate of metabolized BaP and a reduction of their BaP activation potential, as seen by the increased production of conjugated metabolites and the markedly decreased protein-bound active mutagen. PMID- 2109617 TI - The effect of ethanol on platelet function and vascular prostanoids. AB - The present review will discuss the effects of ethanol on platelet function and vascular prostanoids. Whenever possible we have considered human studies because there are marked species differences in platelet function and vascular prostanoid release even in the absence of ethanol. Because of the specialised nature of some parts of the text, we have included brief introductions to help readers who are not familiar with this field. PMID- 2109618 TI - Immunohistochemical localization of prostaglandin H synthase in the embryo and uterus of the mouse from ovulation through implantation. AB - Prostaglandins (PGs) in the embryo and endometrium are involved in processes that are important for implantation. Although the presence of PGs (PGE2, PGF2 alpha, PGI2) in decidualized endometrium has been widely reported, less is known about the capacity of the pre-implantation embryo to synthesize PGs. Prostaglandin H (PGH) synthase is necessary for the production of PGs. Using an immunohistochemical method, PGH synthase was localized in the mouse embryo and uterus from superovulation through embryo implantation. No PGH synthase was detected in oocytes at the time of ovulation or in single-cell embryos 1 day post fertilization (PF). Circular areas of immunostaining became evident in the cytoplasm of blastomeres at the morula stage (day 3 PF). After implantation (day 5 PF), a low level of PGH synthase reactivity was observed in embryonic cells; no PGH synthase was detected in the embryo by day 7 PF. The endometrial glands exhibited maximal immunostaining by day 3 PF, and after implantation, PGH synthase appeared in decidual cells along the border of placentation. Low levels of PGH synthase reactivity were detected in myometrial cells during the period after superovulation through day 7 PF. This is the first demonstration of PGH synthase in the mouse embryo prior to apposition with glandular endometrial epithelium, supporting the hypothesis that the embryo has the potential to produce PGs that may mediate autocrine and/or paracrine responses at the time of nidation. PMID- 2109619 TI - Further characterization of the mouse sperm surface zona-binding site with galactosyltransferase activity. AB - One of the mouse sperm surface binding sites for zona pellucida ligands exhibits galactosyltransferase (GT) enzyme activity. The present study was undertaken to ascertain whether the GT site behaves as a noncatalytic binding site in its physiological capacity, with no glycosylation of zona ligands, or whether glycosylation of zona ligands is an integral part of sperm-zona binding. The effects of Mn2+, the obligatory cation for GT catalysis, on enzyme activity and sperm-zona binding were examined. With uridine-5'-diphosphogalactose (UDPgal) as galactose donor, and N-acetylglucosamine (GlcNAc) as galactose acceptor, increasing concentrations of Mn2+ in the range of 0.1-10 mM increased GT enzyme activity, with half-maximal activation at 0.65 mM Mn2+ (Vmax = 20 pmol/hr/10(6) cells). In the presence of 0-2 mM Mn2+, sperm-zona binding was inhibited in a concentration-dependent manner; 50% inhibition occurred at 1.25 mM Mn2+. At this concentration, GT enzyme activity was at 65% Vmax. To determine the specificity of the GT site for glycoprotein terminal carbohydrate residues, spermatozoa were incubated with, asialo-ovine submaxillary mucin (N-acetylgalactosamine residues), asialo-, -alpha 1-acid glycoprotein (beta 1-4 galactose residues) ovalbumin (Ov; GlcNAc residues), and asialo-agalacto-/alpha 1-acid glycoprotein (AsAgAGP; GlcN Ac residues). Only Ov and AsAgAGP acted as acceptors for galactose in the enzyme assay and inhibitors in the sperm-zona binding assay. The kinetics of the interaction of AsAgAGP with the GT site were determined: the Km was 3.6 mg/ml, with Vmax of 33 pmol/hr/10(6) cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109620 TI - Microtubule-associated proteins. PMID- 2109621 TI - Tau protein and Alzheimer's disease. PMID- 2109622 TI - Neuronal intermediate filaments. PMID- 2109623 TI - Arachidonate metabolism in macrophages is affected by albumin. AB - The incorporation of externally added arachidonic acid into membrane lipids of cultured liver macrophages was found to be strongly inhibited by albumin. Furthermore this protein increased the appearance of radiolabelled arachidonic acid in cell media from [3H] arachidonic acid-prelabelled cells but inhibited almost totally the stimulus-induced formation of prostanoids. Analysis of the membrane lipids revealed that in the presence of albumin arachidonic acid was released to almost the same percentage from all phospholipids, independently of the stimulus. In contrast, in the absence of albumin a significant loss of arachidonic acid was observed for phosphatidylcholine and phosphatidyl-inositol only and the degree of the decrease in label was dependent on the stimulus. Although the exact mechanisms for these actions of albumin are not yet known this protein clearly exerts an inhibitory effect on arachidonic acid incorporation into membrane lipids as well as on the synthesis of different eicosanoids in macrophages; on the other hand albumin leads to an enhanced appearance of arachidonic acid in the cell media. Therefore this protein may be able to control the level of free arachidonic acid within and outside the cell and thereby the conversion of arachidonic acid into eicosanoids. PMID- 2109624 TI - Discriminating between protective and enhancing HIV antibodies. AB - Most attempts to produce a vaccine against HIV-1 infection are utilizing envelope protein components. Hypothetically such vaccine candidates could stimulate production of antibodies that enhance HIV-1 infection via the macrophage route of entry and, consequently, cannot be detected in the conventional neutralization assay. To study this hypothesis we report an assay designed to evaluate the protective/enhancing activity of serum from seropositive immunized or infected individuals. Highly purified activated FcR-bearing monocytes-macrophages were infected with HIV-1 in the presence of the sera, then washed and cocultured with activated peripheral blood mononuclear cells (PBMC) from a normal donor. Productive viral infection, as evaluated by p24 antigen semiquantitative assay in the culture supernatants, allow evaluation of protective/enhancing activity of the sera. The data clearly show that protective rather than enhancing activity is present in the serum of env protein-immunized individuals. PMID- 2109626 TI - Metabolic gas exchange during nitrous oxide anaesthesia with controlled ventilation. AB - A system for metabolic gas exchange has been used during nitrous oxide-opioid anaesthesia incorporating a Servo Ventilator 900 C and external analysers for oxygen and carbon dioxide. Oxygen consumption and carbon dioxide excretion were calculated as differences in content between inspired and expired minute ventilation. Nitrous oxide uptake was calculated similarly, assuming it was the only other gas present in addition to oxygen and carbon dioxide. The mean value for oxygen consumption was 3.25 ml kg-1 min-1, declining by 8% during the 2 h of anaesthesia. The formula for the best fit curve of nitrous oxide uptake was 18.3 . t-0.48 ml kg-1 min-1 when FIN2O was 0.7. To simplify measurement procedures and avoid measurements of expiratory volume, we also calculated metabolic gas exchange when expiratory minute ventilation was expressed as a function of inspiratory minute volume and nitrous oxide uptake. The latter value was obtained from the overall best fit curve for nitrous oxide uptake. PMID- 2109625 TI - Automated non-invasive measurement of cardiac output by the carbon dioxide rebreathing method: comparisons with dye dilution and thermodilution. AB - The accuracy and reproducibility of indirect measurement of cardiac output at rest by the carbon dioxide rebreathing (indirect Fick) method with an automated respiratory analysis system (Gould 9000IV) were compared with simultaneous measurements made in duplicate by dye dilution and thermodilution in 25 patients having cardiac catheterisation studies. Measurements of cardiac output by the carbon dioxide rebreathing method were not significantly different from those obtained with dye dilution (mean difference -0.3 l/min, SD 0.76, 95% confidence interval -0.7 to 0.1). Thermodilution significantly over-estimated cardiac output by a mean of 2.2 l/min or 39% (SD 1.5, 95% confidence interval 1.6 to 2.8) compared with the carbon dioxide rebreathing method and significantly overestimated cardiac output by 1.9 l/min or 31% (SD 1.2, 95% confidence interval 1.2 to 2.5) compared with dye dilution. The reproducibility of measurements of cardiac output in individual patients was satisfactory with the dye dilution method but was poor with carbon dioxide rebreathing and thermodilution. Indirect measurement of resting cardiac output by the Gould 9000IV automated carbon dioxide rebreathing method is more accurate but the variability inherent with this method requires that multiple measurements be taken for each determination. Measurement of cardiac output by the thermodilution method by a commercially available cardiac output computer was not satisfactory because not only was there considerable variability between repeat measurements but the method also consistently overestimated cardiac output compared with the dye dilution method. PMID- 2109627 TI - Carbon dioxide monitoring during high frequency jet ventilation for direct laryngoscopy. AB - To improve ventilation monitoring during direct laryngoscopy, we have developed a high frequency jet ventilator which allows the aspiration of tracheal gas for carbon dioxide analysis (PtCO2) through the injector after stopping the ventilator. In 41 patients undergoing direct laryngoscopy, PaCO2 and PtCO2 were measured simultaneously during high frequency jet ventilation under general anaesthesia. PtCO2 and PaCO2 correlated significantly (r = 0.88), but PtCO2 underestimated PaCO2 by 0.84 (SD 0.72) kPa. The arterial to tracheal PCO2 difference was influenced by airway obstruction. PMID- 2109628 TI - A new infant oscillatory ventilator. AB - A new, simple and inexpensive oscillatory ventilator is described in which a rotating jet mounted in the breathing duct generates cyclically positive and negative pressures in the airway with a sinusoidal flow waveform. Unlike conventional oscillatory ventilators it is free from restrictions to inspiratory or expiratory gas flows and open to atmosphere at all times, making it intrinsically a safe system for ventilation. A prototype rotating jet oscillatory ventilator designed for application in infants was evaluated in rabbits (mean weight 3.8 kg). The positive peak and mean airway pressures were significantly less during oscillatory ventilation at 300 and 420 b.p.m. compared with normal and high frequency positive pressure ventilation at 30 and 300 b.p.m., respectively, while maintaining blood-gas tensions within the normal range. An increase in the oscillatory frequency from 300 to 420 b.p.m. provided no further benefit in terms of airway pressure, tidal volume or blood-gas tensions. PMID- 2109629 TI - Tissue-type plasminogen activator in plasma from breast cancer patients determined by enzyme-linked immunosorbent assay. AB - An enzyme-linked immunosorbent assay (ELISA) using monoclonal and polyclonal antibodies against t-PA was used to measure the concentration of tissue-type plasminogen activator (t-PA) in plasma from 34 healthy donors and 92 breast cancer patients with a varying extent of disease. The mean value of t-PA in plasma for the healthy donors was 2.4 +/- 2.1 ng ml-1 (s.d.). The mean value for the breast cancer patients was 5.3 +/- 4.3 ng ml-1. This increase was statistically significant at the 1% level. There was a positive correlation between the mean t-PA plasma concentration and the extent of disease in different groups of patients. Taking 5.0 ng ml-1 as cut-off point, about 40% of the patients were positive, and 6% of the normal controls were false positive. Twenty five per cent of the patients in complete remission, 28% of the patients with minimal tumour burden, 60% of the patients with moderate tumour burden, and 90% of the patients with massive tumour burden were positive. It is possible that the patients with an elevated plasma t-PA represent a group with a particularly bad prognosis. PMID- 2109630 TI - Oral tegafur in the treatment of gastrointestinal tract cancers: a phase II study. AB - Fifty patients affected by histologically confirmed gastrointestinal tract cancer (GTC) were treated with oral tegafur (TG) 1,000 mg m-2 p.o. on days 1-14 repeated after a 14 day interval. Out of 42 evaluable patients seven patients had a partial response (PR. 17%) with a median duration of 20.5 weeks, three had a minimal response (7%) with a median duration of 23.7 weeks, nine showed a stabilisation which lasted a median of 31.3 weeks, and 23 progressed (55%). No response was obtained in patients affected by carcinoma of the pancreas and the hepatobiliary system. All PRs were achieved in patients with metastatic disease to the liver. No response was seen in patients with bone, lung or nodal metastasis. Three PRs were obtained in patients resistant to 5-fluorouracil. The difference in survival between patients who achieved PR and those who had a stabilisation was not statistically significant. On the other hand the survival of patients with PR was significantly longer than that of patients who progressed. Oral TG was well tolerated by most patients. WHO grade 1-2 gastrointestinal and neurological toxicities were seen respectively in 36% and 25% of cases. Five patients had grade 3 nausea/vomiting and one had grade 3 diarrhoea. Our data suggest that oral TG is effective in the treatment of stomach and colorectal cancers. PMID- 2109631 TI - Long-term toxicity of chemotherapy for testicular cancer--the cost of cure. AB - Twenty-seven patients cured of advanced testicular cancer by cisplatin-based chemotherapy have been assessed, a median of 30 months after start of treatment, for the long-term effects of such treatment on renal, endocrine, audiometric, reproductive and respiratory function. To control for the effects of orchidectomy on endocrine function a similar group of 11 patients cured by orchidectomy alone was also assessed. The extents of impairment in hearing and renal function were related to the total dose of cisplatin received, while the majority of patients had respiratory impairment which was, in part, related to the total dose of bleomycin. TSH was significantly higher in the chemotherapy group although serum free thyroxine and free T3 were normal in all. FSH was raised in 67% of the chemotherapy group although serum free thyroxine and free T3 were while LH was raised in 75% and 45% respectively. Serum testosterone was normal in all. The levels of FSH and LH were both independently correlated with age of the patient while FSH was higher in patients having more chemotherapy and had a tendency to fall towards normal with time since treatment. Over half the patients had normal sperm concentrations although 74% had a raised proportion of abnormal sperm. Indices of sperm function were worse in patients having more chemotherapy but sperm number increased towards normal with time since treatment, particularly after the second year. The long-term side-effects of chemotherapy for testicular cancer are thus generally mild but are largely irreversible and their severity is related to the total amount of chemotherapy received. As their longer term significance is not clear we would recommend that, in the treatment of testicular cancer, doses of chemotherapy are reduced to the minimum required for cure. Assessment of long-term side-effects of chemotherapy for testicular cancer should be a mandatory part of any study of such treatment and should be considered in any comparison of different therapies. PMID- 2109632 TI - Evidence for reactivity of serine-74 with trans-4-(N,N dimethylamino)cinnamaldehyde during oxidation by the cytoplasmic aldehyde dehydrogenase from sheep liver. AB - A nucleophilic group in the active site of aldehyde dehydrogenase, which covalently binds the aldehyde moiety during the enzyme-catalyzed oxidation of aldehydes to acids, was acylated with the chromophoric aldehyde trans-4-(N,N dimethylamino)cinnamaldehyde (DACA). Acyl-enzyme trapped by precipitation with perchloric acid was digested with trypsin, and the peptide associated with the chromophoric group was isolated and shown to be Gln-Ala-Phe-Gln-Ile-Gly-Ser-Pro Trp-Arg. After redigestion with thermolysin, the chromophore was associated with the C-terminal hexaresidue part. If the chromophore is attached to this peptide, serine would be expected to bind the aldehyde and lead to the required acylated derivative. Differential labeling experiments were performed in which all free thiol groups on the acylated enzyme were blocked by carboxymethylation. The acyl chromophore was then removed by controlled hydrolysis and the protein reacted with [14C]iodoacetamide. No 14C-labeled tryptic peptides were isolated, suggesting that the sulfur of a cysteine cannot be the acylated residue in the precipitated acyl-enzyme. PMID- 2109633 TI - Evidence for transition-state stabilization by serine-148 in the catalytic mechanism of chloramphenicol acetyltransferase. AB - The function of conserved Ser-148 of chloramphenicol acetyltransferase (CAT) has been investigated by site-directed mutagenesis. Modeling studies (P. C. E. Moody and A. G. W. Leslie, unpublished results) suggested that the hydroxyl group of Ser-148 could be involved in transition-state stabilization via a hydrogen bond to the oxyanion of the putative tetrahedral intermediate. Replacement of serine by alanine results in a mutant enzyme (Ala-148 CAT) with kcat reduced 53-fold and only minor changes in Km values for chloramphenicol and acetyl-CoA. The Ser-148-- -Gly substitution gives rise to a mutant enzyme (Gly-148 CAT) with kcat reduced only 10-fold. A water molecule may partially replace the hydrogen-bonding potential of Ser-148 in Gly-148 CAT. The three-dimensional structure of Ala-148 CAT at 2.34-A resolution is isosteric with that of wild-type CAT with two exceptions: the absence of the Ser-148 hydroxyl group and the loss of one poorly ordered water molecule from the active site region. The results are consistent with a catalytic role for Ser-148 rather than a structural one and support the hypothesis that Ser-148 is involved in transition-state stabilization. Ser-148 has also been replaced with cysteine and asparagine; the Ser-148----Cys mutation results in a 705-fold decrease in kcat and the Ser-148----Asn substitution in a 214-fold reduction in kcat. Removing the hydrogen bond donor (Ser-148----Ala or Gly) is less deleterious than replacing Ser-148 with alternative possible hydrogen bond donors (Ser-148----Cys or Asn). PMID- 2109634 TI - The N2-guanine adduct but not the C8-guanine or N6-adenine adducts formed by 4 nitroquinoline 1-oxide blocks the 3'-5' exonuclease action of T4 DNA polymerase. AB - When O-acetyl-4-(hydroxyamino)quinoline 1-oxide (Ac-4HAQO) reacts with double stranded DNA at 37 degrees C the major products, N2-guanine, C8-guanine, and N6 adenine adducts, are formed in the proportions of 5:3:2, respectively. When the reaction is carried out with single-stranded DNA at 0 degree C, the products are found in the ratio 1:7:2. Unique 174-bp DNA fragments were modified in these ways and used as substrates for the 3'-5' exonuclease activity of T4 DNA polymerase. The results obtained showed that the exonuclease is blocked by the N2-guanine adduct but not the other two adducts. Interpretation of the cleavage patterns suggested that the enzyme stopped 2 nucleotides before the N2-guanine adduct. The N2-guanine adduct lies in the minor groove of the DNA double helix, while the other two adducts are found in the major groove. Apparently, only the former hinders progression of the enzyme. PMID- 2109635 TI - Activation of the nickel-deficient carbon monoxide dehydrogenase from Rhodospirillum rubrum: kinetic characterization and reductant requirement. AB - The requirements for and kinetics of the activation of the nickel-deficient (apo) CO dehydrogenase from Rhodospirillum rubrum by exogenous nickel have been investigated. The activation is strictly dependent upon the presence of a low potential one-electron reductant. Sodium dithionite and reduced methylviologen (E degrees' = -440 mV) are suitable reductants, whereas reduced indigo carmine (E degrees' = -125 mV) and the two-electron reductants sodium borohydride, NADH, and dithiothreitol are ineffective in stimulating activation. The midpoint potential for activation was observed at approximately -475 mV. The ability of a reductant to stimulate activation is correlated with the reduced state of the enzyme Fe4-S4 centers. The activation follows apparent first-order kinetics in a saturable fashion, yielding a rate constant of 0.157 min-1 at saturating concentration of nickel. The initial rate at which the enzyme is activated by NiCl2 is also a saturable process, yielding a dissociation constant (KD) of 755 microM for the initial association of nickel and enzyme. Cadmium(II), zinc(II), cobalt(II), and iron(II) are competitive inhibitors of nickel activation with inhibition constants of 2.44, 4.16, 175, and 349 microM, respectively. Manganese(II), calcium(II), and magnesium(II) exhibit no inhibition of activation. PMID- 2109636 TI - Heat shock induces a decrease in incorporation of 8-azidoadenosine 5' triphosphate into a 42 kilodalton protein in Drosophila salivary glands. AB - The ATP photoaffinity analogue 8-azidoadenosine 5'-triphosphate (8N3ATP) was used to identify changes which occur in ATP binding proteins in Drosophila salivary glands following heat shock. Photolabeling experiments were done on salivary gland homogenates. Photoincorporation of 8N3ATP was observed in several proteins in both 25 degrees C control and 35 degrees C heat-shocked samples. A 42 kDa protein showed a decrease in the level of photoincorporation observed at saturation with the analogue following heat shock. A 2 min heat shock is enough to induce the effect. Protection against photolabeling was observed with low concentrations (5 microM) of ATP, while excess GTP did not protect, demonstrating that the nucleotide binding site is specific for ATP. The change is rapid enough to suggest that it is one of the earliest cellular changes in response to heat shock. PMID- 2109637 TI - Luminal and basolateral polyamine uptake by rat small intestine stimulated to grow by Phaseolus vulgaris lectin phytohaemagglutinin in vivo. AB - Luminal and basolateral uptake of polyamines by the rat small intestine was studied in vivo. In the concentration range studied (0.1-5 mg per rat) 23-47% of the individual polyamines given intragastrically were found in the body after 1 h, with the small intestine retaining 4-12% of the dose. With spermidine or spermine, labelled polyamines accounted for 85-96% of the counts in the small intestine and between 72-82% were in the form given. However, with putrescine only 29-39% of the label found in the tissue remained in polyamine form and even less, 11-15%, as putrescine. Luminal uptake of polyamines was linear, non saturable and was not stimulated when small intestinal growth was stimulated by phytohaemagglutinin (PHA). On the basolateral side of the gut, polyamine uptake was stimulated by PHA in a time-dependent way in advance of detectable growth. Overall polyamine recoveries were high (89-99%) with intraperitoneally administered spermidine and spermine. Moreover, a large proportion of the counts in the tissue (63-89%) were still in the original form. Even with putrescine, total recoveries of polyamines (72-88%) and putrescine (24-33%) were elevated in comparison with those from the lumen. Treatment of rats with alpha difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, reduced tissue polyamine content, although it had slight effects only on basolateral polyamine transport. The PHA-stimulated increase of polyamine uptake was not abolished in the presence of DFMO. PMID- 2109638 TI - Five percent carbon dioxide challenge: valid analogue and marker of panic disorder? AB - The administration of 5% carbon dioxide (CO2) to patients with panic disorder (PD) induces a behavioral response similar to a naturally occurring panic attack. This article reviews the literature on the nature and incidence of this response. We conclude that the 5% CO2 challenge test is a valid and useful laboratory analogue of naturally occurring panic attacks, and shows promise as a marker to identify a subset of PD patients. Though further research on reliability, validity, and dose-response effects must be conducted, the CO2 challenge test provides important information regarding the phenomenology of panic states. PMID- 2109639 TI - The effects of lithium carbonate on healthy volunteers: mood stabilization? AB - A 2-month lithium-placebo double-blind cross-over study was carried out with 17 healthy volunteers. Their mood was self-rated: twice daily (AM, PM) with the Visual Analogue Mood Scale (VAMS); weekly with the analogue scales for subjective states and body symptoms; and three times (basal and at the end of each treatment period) with the Profile of Mood States (POMS). Memory and reaction time were also assessed, but did not show any change. The mean VAMS score decreased during lithium treatment, but the mean mood variability, a measure of the mean successive differences between consecutive mood ratings (delta squared), did not change significantly. There was a tendency toward decreased mood variability on lithium, both during the full 1-month treatment period and in the last week of treatment, when all volunteers had a lithium serum level ranging from 0.6 to 1.0 mEq/liter. The lower mean VAMS scores on lithium could be attributed to lithium induced dysphoric mood as recorded on the analogue scales and POMS. However, very large inter- and intraindividual differences in response to lithium were observed. Actually, lithium even had an opposite effect on some volunteers' mood. The data and problems involved with assessment of mood and its changes are discussed. PMID- 2109640 TI - Effects of thyrotropin-releasing hormone on blood pressure and heart rate in phobic and panic patients: a pilot study. PMID- 2109641 TI - Reduced cell membrane affinity for lithium ion during maintenance treatment of bipolar affective disorder. PMID- 2109642 TI - Effect of hyperventilation on seizure length during electroconvulsive therapy. PMID- 2109643 TI - Pharmacokinetics and absolute bioavailability of ibuprofen after oral administration of ibuprofen lysine in man. AB - The lysine salt of d,l-2-(4-isobutylphenyl)-propionic acid (ibuprofen lysine) was administered as a single oral dose of 500 mg by means of commercially available coated tablets (Imbun).* To assess the absolute bioavailability of ibuprofen after its oral application as a lysine salt, intravenous injections of ibuprofen solutions containing 200 mg and 400 mg of the drug served as reference application. In a partially randomized cross-over design, 8 healthy male volunteers received three different single dose administrations which were separated by wash-out periods of 4 days each. Ibuprofen plasma concentrations were determined by HPLC using direct injection, pre-column enrichment and column switching techniques. From the results of intravenous injections one can deduce linear ibuprofen pharmacokinetics within the considered dosage range, with corresponding AUC0-infinity values of 3786 micrograms * min ml-1 and 7260 micrograms * min ml-1 for the 200 mg and 400 mg doses, respectively. The values of plasma clearances as well as those of different volumes of distribution showed remarkable constancy after evaluation from both intravenous injections. The absorption of orally administered ibuprofen lysine proved to be rapid, resulting in a mean peak plasma level (Cmax) of 31 micrograms ml-1 ibuprofen and in a mean time to peak (tmax) of 45 min. The absolute bioavailability of ibuprofen amounts to 102.7 per cent, indicating a complete absorption of ibuprofen when administered as its lysine salt. Drug tolerability was excellent for the oral administration of ibuprofen lysine as well as for the intravenous treatments with ibuprofen free acid. Only mild and transient adverse drug reactions such as mild burning or dragging sensation during injection or mild redness at the site of injection were reported. PMID- 2109644 TI - Purification and characterization of factor VIII 372-Cys: a hypofunctional cofactor from a patient with moderately severe hemophilia A. AB - We have purified factor VIII from a patient with moderately severe hemophilia A (FVIII, 4 U/dL; FVIII:Ag, 110 U/dL) and subjected the protein to Western blot analysis after time course activation with thrombin. The cross reacting material positive (CRM+) FVIII has the normal distribution of heavy and light chains before thrombin activation, and, after incubation with the enzyme, appropriate cleavages are made at positions 740 and 1689. However, the normal thrombin cleavage at position 372 in the heavy chain of this molecule does not occur. This result is consistent with the demonstration in the patient's leukocyte DNA of a C to T transition in codon 372, leading to the substitution of a cysteine for an arginine residue at the heavy chain internal cleavage site. The severely impaired functional activity of this molecule confirms that the heavy chain of FVIII must be proteolysed in order to effect full cofactor activation in vivo. However, a threefold activation was detected when this protein was incubated with thrombin. No evidence of thrombin-mediated cleavage at position 336 in the heavy chain was detected, in contrast to the variant recombinant B domainless-molecule, FVIII 372 Ile, described by Pittman and Kaufman (Proc Natl Acad Sci USA 85:2429, 1988). Using gel permeation studies of the FVIII/von Willebrand factor (vWF) complex before and after thrombin activation, we have demonstrated that the 40 Kd A2 domain of wild type FVIII dissociates from vWF after cleavage by the enzyme. In contrast, incomplete dissociation was detected in the case of FVIII 372-Cys. We conclude that the functional defect in FVIII 372-Cys is a consequence of the resistance to proteolysis of the internal scissile bond in the heavy chain. PMID- 2109645 TI - Growth, photosynthesis and nitrogen fixation of Anabaena doliolum exposed to assam crude extract. PMID- 2109646 TI - Intramural pseudodiverticulosis of the esophagus in corrosive strictures: report of three cases. AB - First described in 1960, esophageal intramural pseudodiverticulosis (EIPD) is a rare disease characterized by narrow-necked diverticuli confined to the esophageal wall. The cause is debatable, but esophageal strictures commonly accompany this entity. The association with EIPD of strictures caused by corrosives has been reported only once to date. We describe three additional examples. PMID- 2109647 TI - Plasma gonadotropin patterns characterizing the development of polycystic ovaries in the estradiol valerate treated rat. AB - Polycystic ovaries (PCO) develop in female rats within 4 weeks of an injection of estradiol valerate (EV). The final morphological transition from a noncystic to a cystic state occurs in the presence of estrous (control) mean serum gonadotropin concentrations, suggesting that gonadotropin patterns rather than mean concentrations are causal to PCO. We have examined plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) patterns in female rats at estrus and on days 5, 11, 16, and 21 following EV treatment. Estrous animals displayed large amplitude LH pulses of short duration, interspersed among frequent, low amplitude pulses of similar duration, and infrequent, broad-based LH episodes. Following EV treatment, there was a progressive decline in the frequency and magnitude of the large amplitude LH pulses, such that by day 16, they ceased altogether. Conversely, the frequency of the low amplitude pulses increased such that the total pulse frequency remained constant. The onset of this pattern coincides with the wave of atresia that precedes the emergence of cystic follicles. The pulsatile plasma pattern of FSH seen at estrus remained unaltered at all time intervals examined after EV treatment. We conclude that there is a specific LH pattern responsible for the generation and maintenance of the PCO condition. PMID- 2109648 TI - Scrapie and human neurodegenerative diseases. PMID- 2109649 TI - Residual proliferative capacity in F9 teratocarcinoma stem cell cultures treated with alpha-difluoromethylornithine, an inducer of parietal endoderm differentiation. AB - We have previously shown that inhibition of polyamine biosynthesis by treatment with 5 mM alpha-difluoromethylornithine (DFMO) causes growth arrest and induces differentiation of F9 teratocarcinoma stem cells. The resulting phenotype is similar to that of parietal endoderm, and these differentiated cells possess no apparent proliferative capacity. In the present study, however, it is demonstrated that some of the DFMO-treated cells are not terminally differentiated. Upon a change to DFMO-free growth medium these cells eventually start to proliferate. Using a colony forming efficiency assay, it is estimated that less than 1 out of 200,000 cells retains its proliferative capacity after 6 10 days of DFMO treatment. These cells exhibit no apparent resistance to DFMO, and their population doubling time is similar to that of untreated control F9 cells. Consequently, the possible existence of a small, quiescent, cell population possessing proliferative potential must be taken into account when designing therapeutic protocols for DFMO. PMID- 2109650 TI - The cytotoxicity of Pseudomonas exotoxin A, inactivated by modification of the cell-binding domain I, is restored when conjugated to an erythroid cell-specific targeting agent. AB - To be capable of selective killing of tumor cells, the non-selective Pseudomonas aeruginosa exotoxin A must have its cell-binding domain inactivated or removed and then be chemically linked to, or genetically fused with, a specific targeting agent. In the present study, epsilon-NH2 groups of lysine residues of the cell binding domain of exotoxin A were extensively propionylated with N-succinimidyl-3 propionate (NSP). The NSP-treated exotoxin retained its cytocidal ADP ribosyltransferase activity, but it could no longer bind to, and inhibit the proliferation of, Friend murine erythroleukemia cells. Cytotoxicity (i.e., the ability to inhibit proliferation) for the Friend erythroid cells was restored completely to the NSP-inactivated exotoxin by conjugating it to ADIF, an autocrine factor secreted by chicken erythroleukemia cells which selectively inhibits the differentiation of erythroid cells such as Friend erythroleukemia cells without inhibiting their proliferation. PMID- 2109651 TI - Modulation of nicotinamide adenine dinucleotide and poly(adenosine diphosphoribose) metabolism by calicheamicin gamma 1 in human HL-60 cells. AB - The mechanism of calicheamicin gamma 1-mediated cytotoxicity was studied in human promyelocytic HL-60 leukemic cells. Calicheamicin gamma 1 caused an increase in poly(ADP-ribose) polymerase activity in HL-60 cells parallel to cell death. This effect of the drug correlated with a decrease in intracellular NAD+ level. 3 Aminobenzamide, an inhibitor of poly(ADP-ribosylation), prevented the calicheamicin gamma 1-triggered cytotoxicity in a dose-dependent manner. Simultaneous with the reversal of cytotoxicity, the addition of 3-aminobenzamide to drug-treated cells also inhibited the increase in poly(ADP-ribosylation) and the reduction in cellular NAD+ content. These results indicate that poly(ADP ribosylation) activation and the subsequent perturbations in NAD(+)-dependent metabolic reactions are associated with the cytotoxic properties of the antitumor antibiotic calicheamicin gamma 1. PMID- 2109652 TI - Inhibition of liver microsome-mediated mutagenesis, metabolism and DNA-binding of benzo[a]pyrene and benzo[a]pyrene 7,8-dihydrodiol in the rat following glucose administration. AB - Aroclor 1254-induced rat liver microsomes prepared from control and glucose treated rats (30% glucose in drinking water 48 h prior to sacrifice) were used in studies of benzo[a]pyrene (BaP) and BaP 7,8-dihydrodiol (BaP 7,8-DHD)-induced mutagenesis in Salmonella typhimurium TA100. Microsome-dependent metabolism and metabolite binding of BaP and BaP 7,8-DHD to calf thymus DNA was also investigated. BaP-induced mutagenesis in TA100 was inhibited 27% and BaP 7,8-DHD induced mutagenesis was inhibited 55% by microsomes from glucose-treated rats. [3H]BaP and [3H]BaP 7,8-DHD metabolite binding to DNA was inhibited 17% and 20%, respectively. High performance liquid chromatographic (hplc) analysis of enzyme hydrolyzed DNA yielded 7R and 7S-diol epoxide-1 deoxyguanosine (BPDE-1:dG) adducts and BPDE-2:dG adducts of [3H]BaP and [3H]BaP 7,8-DHD. These adducts were inhibited 38% and 50%, respectively, by microsomes from glucose-treated rats. Hplc analysis of organosoluble metabolites of [3H]BaP and [3H]BaP 7,8-DHD showed an inhibition of metabolism of 28% and 50%, respectively, by microsomes from glucose-treated rats. The inhibition of metabolism correlated with the effect of glucose treatment on inhibition of BaP and BaP 7,8-DHD-induced mutagenesis and adduct formation. These results suggest that the mechanism by which glucose produces its effects on mutagenesis, DNA-binding and adduct formation is by an inhibition of microsome-mediated metabolism of BaP and BaP 7,8-DHD. PMID- 2109653 TI - Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with D,L-alpha difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet. AB - The effect of three levels of piroxicam and three levels of D,L-alpha difluoromethylornithine (DFMO) fed individually and in combination during the postinitiation phase of carcinogenesis was studied in male F344 rats to generate a data base on the efficacy and synergistic and additive effects of these compounds as inhibitors of colon carcinogenesis. The maximum tolerated dose of DFMO was determined in male F344 rats and found to be 5000 ppm in the AIN-76A diet. Piroxicam at levels of 25, 75, and 150 ppm and DFMO at concentrations of 400, 1000, and 4000 ppm (20, 50, and 80% maximum tolerated dose) in AIN-76 diet were tested individually and in combinations. At 7 weeks of age, while the rats were consuming the control diet (AIN-76A), all animals except the vehicle (saline)-treated controls were given a single s.c. injection of azoxymethane (CAS: 25843-45-2) at a dose level of 29.6 mg/kg body weight to induce intestinal tumors. One week after azoxymethane injection, animals were transferred to their respective experimental diets containing piroxicam and DFMO. Fifty-six weeks after azoxymethane injection, all animals were necropsied and colon and small intestinal tumor incidences and multiplicity were compared among the various dietary groups. Feeding of diets containing 75 and 150 ppm piroxicam or 1000 and 4000 ppm DFMO significantly inhibited the incidence (percentage of animals with tumors) of colon adenocarcinomas compared to that of control diet. The multiplicity (number of tumors/rat) of adenocarcinomas was significantly inhibited in animals fed the 25, 75, and 150 ppm piroxicam or 400, 1000, and 4000 ppm DFMO diets. Results analyzed by the linear regression method suggested a dose dependent inhibition in colon adenocarcinoma incidence with increasing levels of piroxicam or DFMO. The incidence and multiplicity of colon adenocarcinomas were significantly inhibited in animals fed the diets containing combinations of 25, 75, and 150 ppm piroxicam and 400, 1000, and 4000 ppm DFMO. Piroxicam and DFMO administered together had a stronger inhibitory effect than did those given individually. Piroxicam and DFMO when administered individually had no significant inhibitory effect on colon adenoma incidence and multiplicity; in contrast, combinations of these compounds significantly inhibited colon adenomas. No consistent differences were found in the incidence and multiplicity of small intestinal tumors among the dietary groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2109654 TI - Defective postreplication repair in xeroderma pigmentosum variant fibroblasts. AB - Postreplication repair (PRR) was quantified in normal human fibroblasts and in xeroderma pigmentosum (XP) variant fibroblasts after treatment with UV or benzo[a]pyrene diol epoxide-I (BPDE-I). PRR may be defined as the elimination of discontinuities in the daughter-strand DNA and the replicative bypass of lesions in the DNA template. Pathways of PRR reduce the number of DNA growing points that are blocked at template lesions and increase the rate of growth of nascent DNA on damaged templates. Rates of DNA synthesis and strand growth were measured in solvent- and carcinogen-treated cells by velocity sedimentation analyses of radiolabeled nascent DNA in alkaline sucrose gradients. Logarithmically growing normal fibroblasts displayed D0 values of 6.3 J/m2 and 0.37 microM for the inhibition of DNA synthesis in active replicons by UV and BPDE-I, respectively. Under identical conditions, the XP variant cells exhibited D0 values of 1.5-2.0 J/m2 and 0.27-0.31 microM. Pulse-chase experiments were performed in cells synchronized at the beginning of the S phase. Normal and XP variant cells displayed inhibition of DNA strand growth by UV, with D0 values of 21.6 and 7.0 J/m2, respectively. The D0 values for the inhibition of DNA strand growth by BPDE I were 0.85 microM for the normal cells and 0.62-0.79 microM for the XP variant cells. The inhibitions of DNA replication by UV and BPDE-I were also analyzed in terms of DNA lesion frequencies. Based on the D0 values for inhibition of DNA replication, we concluded that the XP variant cells express maximally 25-33% of the total PRR activity observed in normal fibroblasts after UV treatment. Conceivably, this deficiency in PRR activity results in the XP variant's increased risk of cancers induced by sunlight, because XP variant cells and normal fibroblasts are equally proficient in excision repair. Both normal and XP variant fibroblasts, however, displayed similar PRR activities in response to BPDE-I treatment. PMID- 2109655 TI - Metabolic activation of aflatoxin B1 and 2-amino-3-methylimidazo[4,5-f]-quinoline by human adult and fetal livers. AB - The mutagenic activation of promutagens by human adult and fetal livers was investigated using the umu test system. Among the promutagens studied, aflatoxin B1 (AFB1) and 2-amino-3-methyl-imidazo[4,5-f] quinoline (IQ) were efficiently activated to mutagens by both adult and fetal livers. 7,8-Benzoflavone inhibited the activation of IQ by fetal livers, but the inhibition observed in fetal livers was much less than that observed in adult livers. Antibodies to P450HM1 (P450111A4) and P450HFLa markedly inhibited the activation of AFB1 by adult and fetal livers, respectively. The formation of genotoxic product(s) from IQ in human adult livers was almost completely inhibited by anti-P448H (P4501A2) antibodies but not by anti-P450HM1 antibodies, whereas that in fetal livers was inhibited by both anti-P450HFLa and anti-P450IA2 antibodies. P450HFLa catalyzed the mutagenic activation of both AFB1 and IQ in a reconstituted system. On the contrary, P450HM1 catalyzed the mutagenic activation of AFB1 but not IQ. A preparation of cytochrome P450 partially purified from human fetal livers and cross-reactive with anti-P450IA2 antibodies was found to be active for mutagenic activation of IQ in a reconstituted system. These results indicate that P450HFLa and P450HM1 are mainly involved in the genotoxic product formation from AFB1 in fetal and adult livers, respectively, and that the metabolic activation of IQ in fetal livers is catalyzed by two forms of cytochrome P450, P450HFLa, and cytochrome P450 immunochemically related to P450IA2 but that in adult livers it is mainly catalyzed by cytochrome P450 related to P450IA2. PMID- 2109656 TI - Lymphokine-independent, leukemia cell-mediated induction of tumor necrosis factor in human monocytes. AB - Unactivated human blood monocytes and monocytic THP-1 cells were found to respond to some leukemia cells by tumor necrosis factor (TNF) production. The TNF production by THP-1 cells in response to K562 cells was preceded by a rapid rise in [Ca2+]i, initiated within 1 h and terminated within 4 h as a refractory state took over. Neither the amount nor the duration of TNF production was enhanced by gamma-interferon. The P32/ISH cells did not induce a significant [Ca2+]i change of TNF production, while MOLT-4 cells failed to induce TNF despite their capacity to mobilize Ca2+ in THP-1 cells. The failure of P32/ISH or MOLT-4 to induce TNF was attributed primarily to a lack of stimulatory membrane molecules rather than to suppression by an inhibitory component, since liposomes carrying membrane components of K562 and MOLT-4 or P32/ISH in varying proportions elicited TNF production that precisely reflected the K562 proportion. The ability of K562 to induce TNF was selectively impaired by trypsin, whereas the ability to mobilize [Ca2+]i was more sensitive to glutaraldehyde, although once the latter activity was extinguished, the K562 cell could no longer induce TNF. These results suggest that some leukemia cells are equipped with two or more signaling membrane moieties which together stimulate monocytes for transient tumoricidal expression in the preimmune stage. PMID- 2109657 TI - Effect of alpha-difluoromethylornithine on 1,3-bis(2-chloroethyl)-1-nitrosourea and cis-diamminedichloroplatinum(II) cytotoxicity, DNA interstrand cross-linking, and growth in human brain tumor cell lines in vitro. AB - The polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) has been shown to potentiate the cytotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in 9L rat brain tumor cells and in non-central nervous system human cancer cells in vitro, but the effects on a human brain tumor cell line have not been reported. Because BCNU is one of the main chemotherapeutic agents used clinically for the treatment of brain tumors, the effect of DFMO treatment on cell growth and potentiation of cytotoxicity was studied in vitro in U-251 MG and SF-126 cells, human tumor cell lines derived from malignant glioma tissue. Pretreatment of U-251 MG with 1 mM DFMO depleted cells of putrescine and spermidine within 48 h but did not sensitize cells to BCNU treatment even after a pretreatment of 72 h. DFMO treatment had no effect on the number of interstrand cross-links formed in BCNU-treated cells. Even treatment with 5 mM DFMO for 72 h caused only the suggestion of potentiation of BCNU cell kill. In contrast, a 72-h pretreatment with 1 mM DFMO decreased the cytotoxic effect of cis-diammine dichloroplatinum(II) and caused a 38% decrease in the number of DNA interstrand cross-links formed. The glutathione content and cell cycle distribution of U-251 MG cells were not affected by DFMO pretreatment. Because Phase II clinical trials with DFMO and BCNU have shown promise for the treatment of anaplastic astrocytomas in humans, a second brain tumor cell line, SF-126, was studied. In this cell line a consistent potentiation of BCNU cytotoxicity (dose enhancement of 1.2 at the 10% survival level) was observed in cells pretreated with 1 mM DFMO for 72 h. PMID- 2109659 TI - Short incubation with 7-oxo-prostacyclin induces long lasting prolongation of repolarisation time and effective refractory period in rabbit papillary muscle preparation. AB - STUDY OBJECTIVE - To determine whether the long lasting protection from early postocclusion and reperfusion arrhythmias induced by 7-oxo-prostacyclin is due to an anti-ischaemic effect alone or in combination with direct membrane effects. DESIGN - The study was performed on electrically stimulated isolated rabbit papillary muscle preparations with or without incubation with a stable prostacyclin analogue, 7-oxo-prostacyclinephedrine (7-oxo-PgI2). In some experiments, rabbits were pretreated with 7-oxo-PgI2. MEASUREMENTS and RESULTS - Marked prolongation of action potential duration (APD90) and effective refractory period developed 2 h after 20 min incubation with and subsequent washout of 7-oxo PgI2, 1.1 X 10(-8) mol.litre-1. The same occurred if incubation with 7-oxo-PgI2 was maintained throughout the experiment. The only other change was a small diminution in amplitude of the action potential. During the 20 min incubation period neither APD90 nor effective refractory period was affected and only a transitory increase in the maximum rate of depolarisation, disappearing after washout, was seen. During the 4 h observation period there were no changes in the control preparations. The long lasting electrophysiological changes induced by 7 oxo-PgI2 were not affected by 60 min incubation with indomethacin, 2.8 X 10(-6) mol.litre-1. Pretreatment of rabbits with 7-oxo-PgI2, 50 micrograms.kg-1 intramuscularly, 48 h before the experiments prolonged effective refractory period v untreated controls. CONCLUSIONS - 7-oxo-PgI2 induces prolongation of APD90 and effective refractory period in adequately oxygenated normal papillary muscles as well as in ischaemic hearts. Therefore a direct membrane effect may contribute to its antiarrhythmic action, as well as an indirect anti-ischaemic effect. Such a direct effect is unlikely to be related to activation of the degradation products of the arachidonic acid cascade since it was not influenced by indomethacin. PMID- 2109658 TI - Neuropsychological effects of L-deprenyl in Alzheimer's type dementia. AB - The monoaminergic neurotransmission defect seen in dementia of the Alzheimer type (DAT) is linked to a known increased activity of type B cerebral monoamine oxidases (MAO-Bs). The use of drugs that are able to block this abnormal activity could therefore be useful in the treatment of some cognitive deficits that characterize DAT. Twenty patients with a clinical diagnosis of DAT and with a slight-moderate mental deterioration were treated with 10 mg/day of L-deprenyl, a selective MAO-B inhibitor, according to a double-blind crossover design vs. placebo. Initial treatment (drug or placebo) was randomly assigned. The patients' cognitive functions were evaluated at baseline and then after 3 and 6 months of treatment with drug or placebo. The patients crossed over treatment after 3 months, without a washout interval. The results of the study show the higher and statistically significant effects of L-deprenyl on memory and attention that seem to be due to an improved function of the monoaminergic systems involved in the process of neuronal degeneration. PMID- 2109660 TI - Comparison of total costs of administering calcium polycarbophil and psyllium mucilloid in an institutional setting. AB - The total cost of administering calcium polycarbophil per unit dose (two tablets) was compared with that of administering psyllium mucilloid (one packet dissolved in 8 oz of water) in 20 elderly nursing-home residents. Times for printing labels, checking and initialing labels, gathering materials needed, and preparing and administering the medications were recorded during at least 50 observations in each treatment group. Total cost included nurses' and pharmacists' time, materials, and medications. Calcium polycarbophil doses were prepared and administered more quickly (mean, 49.5 sec) than psyllium mucilloid (105.3 sec). The mean cost of preparing and administering a unit dose was 28.2 for calcium polycarbophil tablets and 59.9 for psyllium mucilloid. The results suggest that the use of calcium polycarbophil tablets would save time and money in institutions in which laxatives are frequently administered. PMID- 2109661 TI - Penicillin G, penicillin V, and other pharmaceutical improvements in the treatment of infections. PMID- 2109662 TI - Trafficking and activation of murine natural killer cells: differing roles for IFN-gamma and IL-2. AB - The repeated ip injection of highly purified recombinant IFN-gamma or IL-2 resulted in a local increase in peritoneal NK activity. This increase in lytic activity was paralleled by increases in the number of peritoneal leukocytes reacting with a rat monoclonal antibody directed against the NK cell-associated surface antigen LGL-1. LGL-1 reacts specifically with the majority of murine NK cells in BALB/c and C57BL/6 mice. A single injection of IFN-gamma induced more peritoneal NK activity at 24 hr than IL-2 on a protein basis. Both cytokines induced increases in the number of LGL-1+ peritoneal cells by 24 hr after injection. Simultaneous injection of suboptimal amounts of IFN-gamma (100 U) and IL-2 (10,000 U) resulted in a significant augmentation of peritoneal NK activity over that observed with either cytokine alone. Also, the peritoneal NK activity generated in response to ip injection of high doses of IL-2 (100,000 U) could be dramatically reduced by simultaneous injection of a neutralizing monoclonal antibody to IFN-gamma. Administration of IFN-gamma 1 day prior to IL-2 resulted in a significant augmentation of the NK activity above that observed with the individual cytokines. In contrast, injection of IL-2 prior to IFN-gamma did not enhance NK activity over that observed with the individual cytokines. Both cytokines must be injected ip for the complementary effects of IFN-gamma and IL-2 on peritoneal NK activity to occur. In contrast, in vitro incubation of peritoneal leukocytes with IFN-gamma resulted in neither a significant enhancement of NK lytic activity nor an increase in the number of LGL-1+ cells. In vitro treatment of peritoneal leukocytes with IL-2 always resulted in significant augmentation of NK lytic activity in the absence of any increase in the number of LGL-1+ cells. These data are consistent with the hypothesis that the local release of IFN-gamma increases peritoneal NK activity by promoting the influx of blood-borne LGL-1+ NK cells from other sites. In contrast, low doses of IL-2 augment the lytic activity of local resident NK cells, whereas high doses of this cytokine induce both an activation of local NK cells and emigration of LGL 1+ NK cells from other sites due to the endogenous generation of IFN-gamma within the peritoneal cavity. Therefore, the local release of IFN-gamma may play an important role in regulating NK cell infiltration in vivo. PMID- 2109663 TI - Natural anti-chondrocyte cytotoxic activity in the mouse: supportive role of macrophages. AB - The role of macrophages (M phi) in natural anti-chondrocyte cytotoxic activity of normal murine splenocytes (SPL) and peritoneal cells (PC) was examined by means of an 18-hr 51Cr-release assay. Removal of M phi by either plastic adherence or carbonyl iron and magnet resulted in significant (P less than 0.01) reduction of SPL-mediated lysis of chondrocytes. It, however, did not influence natural anti YAC-1 leukemia activity. On the contrary, M phi-depleted suspensions of PC retained their anti-chondrocyte activity at the initial level. Neither adherent SPL nor adherent PC exerted significant anti-chondrocyte cytotoxicity. The activity of nonadherent SPL could be, however, restored by reconstitution with the graded numbers of syngeneic adherent spleen- or peritoneal cavity-derived cells. Restoration of anti-chondrocyte activity of nonadherent SPL to the level comparable with that of untreated SPL was achieved with about 10% of adherent cells. On the other hand, reconstitution of nonadherent PC did not result in an increase of chondrocyte lysis. Potentiation of nonadherent SPL activity was seen only with syngeneic M phi, and the latter could not be replaced by conditioned media which were generated in the 18-hr culture of adherent SPL or PC. PMID- 2109664 TI - Effect of CGS 9896 on stress-induced gastric ulcer in rat. AB - 1. The effects of CGS 9896, a partial benzodiazepine agonist, and chlordiazepoxide, a full benzodiazepine agonist, on stress-induced gastric ulcers as well as blood glucose were compared. 2. Ulceration in the glandular stomach was induced by 2 h restraint at 4 degrees C. 3. CGS 9896 reduced significantly the ulcer parameters but did not affect blood glucose. The effect of CGS 9896 was dose-dependently blocked by the benzodiazepine antagonist flumazepil. 4. Chlordiazepoxide reduced the ulcer parameters but increased blood glucose. 5. Since CGS 9896 lacks sedative effects but reduced ulcer parameters, the anti ulcer and sedative effects of drugs acting at benzodiazepine receptors are disassociated. 6. Benzodiazepine-induced hyperglycaemia does not play a major role in the anti-ulcer effects. PMID- 2109665 TI - Relationship between steady-state plasma nizatidine concentrations and inhibition of basal and stimulated gastric acid secretion. AB - Steady-state plasma nizatidine concentrations were related in a linear fashion to nizatidine infusion rate. Infusion rates of 2.5, 10, and 20 mg/hr resulted in mean plasma nizatidine concentrations of 69, 247, and 575 ng/ml. Basal acid secretion was inhibited by 50% and 90% at mean plasma nizatidine concentrations of 60 and 430 ng/ml. Protein-stimulated acid secretion was inhibited by 50% and 90% at mean plasma nizatidine concentrations of 75 and 490 ng/ml. The mean pH of basal gastric secretions was 1.6 during placebo infusion and 4.6 when the mean plasma nizatidine concentration was 575 ng/ml. PMID- 2109666 TI - Purification and characterization of bilirubin UDP-glucuronyltransferase from the liver of eel, Anguilla japonica. AB - 1. The enzyme bilirubin uridine diphosphate glucuronyltransferase (UDPGT) was purified and characterized from the liver of eel, Anguilla japonica. 2. The molecular weight of the enzyme was 88,000. 3. The optimal working pH of the enzyme was 7.5-8.0. The optimal working temperature of the enzyme was around 46 degrees C. 4. The Km of bilirubin and uridine diphosphate glucuronic acid for this enzyme was 1.6 mM and 1.8 mM respectively. 5. The concentration of bilirubin did not show any significant effect of inhibition on this enzyme up to 3.3 mM. 6. Since this is the first time UDPGT has been purified and characterized from poikilothermic aquatic animals, it provided interesting information on evolution and adaptation of this enzyme when compared to that of mammals. PMID- 2109667 TI - Conformational comparison in the growth hormone family. AB - 1. The method of Kubota et al. [Biochim. biophys. Acta 701, 242-252 (1982)] was applied to several members of the growth hormone family in order to examine their conformational homology. 2. The method neither detects differences between rat, cow, sheep, horse and alpaca hormones, nor between monkey and human hormones. 3. Lack of homology between primate and non-primate growth hormones was found in segments 42-49 and 184-191. The first fragment could be linked to species specificity. PMID- 2109668 TI - Regulation and rate of the hexose monophosphate shunt in Rana ridibunda erythrocytes. AB - 1. Resting rates of Rana ridibunda erythrocyte glucose consumption and 14CO2 production from 1-14C-glucose were found to be significantly lower than the respective values in human erythrocytes. 2. In the presence of 1-14C-glucose Methylene Blue stimulated 14CO2 production 7-fold, while in the presence of 6-14C glucose Methylene Blue stimulated 14CO2 production 1.2-fold. 3. The Km of G-6-PD for G-6-P and NADP were 29 and 12 microM, respectively while the Km of 6-PGD for 6-PG and NADP were 83 and 32 microM, respectively. The Ki of G-6-PD and 6-PGD for NADPH were 80 and 12 microM, respectively. 4. Excess amounts of NADP resulted in a significant decrease of 14CO2 production from 1-14C-glucose in total haemolysates. 5. ATP, ADP and fructose diphosphate inhibited both G-6-PD and 6 PGD, the latter being more sensitive than G-6-PD to their inhibitory effect, 2,3 DPG and reduced and oxidized glutathione showed a marked inhibitory effect on 6 PGD, while the phosphorylated trioses inhibited only G-6-PD. 6. Physiological concentrations of oxidized glutathione decreased the inhibition exercised by NADPH on G-6-PD. 7. The possible role of the two dehydrogenases in the regulation of the HMS is discussed. PMID- 2109669 TI - Purification and characterization of glycogen phosphorylase B from skeletal muscle of the mullet Liza ramada: amino acid sequence of the phosphorylation site. AB - 1. Skeletal muscle glycogen phosphorylase b has been purified from Liza ramada (mullet). 2. The Mr of the purified enzyme subunit was found to be 97,000. By gel filtration a relative Mr of 190,000 was found. 3. Proteolytic digestion of 32P phosphorylated mullet phosphorylase gave a [32P]-labelled peptide which is observed to contain Ser, its sequence being -Gln-Ile-Ser-Val-Pro-. 4. During 'in vitro' phosphorylation of mullet phosphorylase, 32P was incorporated in different protein bands resolved by isoelectric focusing. The degree of radioactivity associated with each one changed with the incubation time. PMID- 2109670 TI - Cathepsin D-like activity in the release of Gal beta 1-4GlcNAc alpha 2 6sialyltransferase from mouse and guinea pig liver Golgi membranes during the acute phase response. AB - 1. Rat Gal beta 1-4GlcNAc alpha 2-6sialyltransferase (E.C. 2.4.99.1) is released from Golgi membranes by cleavage of a portion of the enzyme containing the active site from a membrane anchor; this effect was most dramatic during the acute phase response. The enzyme that cleaved sialyltransferase had the properties of cathepsin D was most active at pH 5.6 and was likely of lysosomal origin (Lammers and Jamieson, 1988). 2. The acute phase response of sialyltransferase in mouse and guinea pig was previously found to differ from that in the rat. Release of sialyltransferase from mouse and guinea pig Golgi membranes has now been studied in order to make a comparison with the rat system. 3. Maximum release of sialyltransferase from mouse and guinea pig Golgi occurred at pH 4.6 and 5.2, respectively; like the rat a cathepsin D-like proteinase was responsible for release of both enzymes. 4. Immunoblot analysis showed that membrane-bound rat and mouse sialyltransferase had Mr 49,000, whereas the guinea pig enzyme had Mr 42,000. The released form of the rat enzyme had Mr 42,000, but released forms of mouse and guinea pig enzymes had Mr 38,000 suggesting a different cleavage site for these two enzymes compared to the rat enzyme. PMID- 2109671 TI - Soluble calcium-binding proteins: parvalbumins and calmodulin from eel skeletal muscle. AB - 1. Eel skeletal muscle contains three parvalbumin isoforms. The overall parvalbumin concentration in the muscle is 0.5 mmol kg-1 wet weight. 2. Calmodulin (0.1 mumol kg-1 wet weight) was purified by extraction with ethylenediamine tetraacetate-containing buffer, fractionation with trichloroacetic acid and separation by ion exchange chromatography on DEAE cellulose and by molecular sieving on Ultrogel AcA 54. 3. Troponin-C-free calmodulin was obtained by fast protein liquid chromatography on a Mono Q column. PMID- 2109672 TI - Recurrent postoperative endophthalmitis. AB - We treated five patients for postoperative endophthalmitis who demonstrated an initially good response to intravitreal management of their infection and then suffered a later recurrence. Four of the five patients received a single intravitreal injection of antibiotics as the only intravitreal therapy, and the fifth patient received a single antibiotic injection in addition to a partial vitrectomy. All recurrent infections occurred between 10 and 21 days after the original intravitreal injection of antibiotics. At the time of the recurrence, all five patients remained culture positive with the same organism that was initially isolated. The bacterial species isolated were S. epidermidis, group D streptococcus, P. acnes, P. mirabilis, and P. aeruginosa. All patients were ultimately sterilized with repeated intravitreal injections of antibiotics, vitrectomy, and/or intraocular lens removal. Factors that were related to recurrent infection were marginal susceptibility of the organism to the originally injected antibiotics, infection with a slowly replicating organism, and infection with a gram-negative bacillus. A single intravitreal injection of antibiotics may only partially treat bacterial endophthalmitis. Patients should be observed for at least 3 weeks following treatment of endophthalmitis for recurrence of their infection, and aggressive management, including vitrectomy and repeated intravitreal injections of antibiotics, should be used to treat recurrent infections. PMID- 2109673 TI - Influence of parenteral nutrition on rates of net substrate oxidation in severe trauma patients. AB - Optimal nutritional support should use a patient's energy expenditure as a guide for administering sufficient but not excessive caloric intake. Eight patients requiring parenteral nutrition were evaluated, using indirect calorimetry measurements, to determine the nutritional influence on the rates of substrate utilization in the critical period of catabolic illness due to accidental trauma. Five days of total parenteral nutrition, providing calories to match the measured basal resting energy expenditure and N to replace the initial urinary losses a) shifted the RQ from 0.74 +/- 0.03 to 0.81 +/- 0.03, b) improved but could not reverse negative N balance, c) decreased net fat oxidation, d) increased carbohydrate and protein oxidation, e) elevated daily norepinephrine and epinephrine excretion rates, and f) attained positive energy balance. The results suggest that positive energy balance could be achieved in trauma patients by providing total energy intake matching their basal measured energy expenditure plus 7% to 10% for activity energy expenditure. To prevent further loss of lean body mass, an N intake of 350 mg/kg.day was needed in these catabolic ICU patients. PMID- 2109674 TI - Allergic contact dermatitis of the hands from Sporicidin (glutaraldehyde-phenate) used to disinfect endoscopes. PMID- 2109675 TI - Neonatal scabies. AB - A case of scabies infestation in a ten-week-old infant is described. Infestation in a neonate presents a clinical picture quite different from that found in older children and adults. Therapeutic options can be limited in infants. Current concepts and treatment modalities are discussed. PMID- 2109676 TI - Evaluation of bedside testing options for the critical care unit. AB - Bedside testing offers a unique opportunity for earlier and more specific diagnosis, faster and more frequent monitoring, and the opportunity to improve patient care and reduce hospital costs. However, if abused it may not improve patient care and may increase hospital costs. In the future, more clinical studies will need to be performed to determine which tests are cost-effective. PMID- 2109677 TI - Research issues in assessing addiction treatment efficacy: how cost effective are Alcoholics Anonymous and private treatment centers? PMID- 2109678 TI - Aldose reductase inhibitors in the treatment of diabetic neuropathy. A review of the rationale and clinical evidence. AB - This review considers the definition of clinical diabetic neuropathy and the theoretical basis for the use of aldose reductase inhibitors in the treatment of distal sensorimotor neuropathy, the most common clinical problem. Myoinositol depletion is related to hyperglycaemia-induced polyol activity, changes which are associated with early functional deficits in acute experimental diabetes. These changes are reversible by the administration of aldose reductase inhibitors, and this provides the rationale for the treatment of human diabetic neuropathy with these agents. Many early trials of these drugs have produced some evidence of clinical benefit in patients with diabetic neuropathy, but interpretation of data is difficult as patient selection and neuropathy definition are not yet standardised. In addition, it is possible that once the neuropathic process is initiated, there is a point where it becomes irreversible, and treatment with aldose reductase inhibitors may therefore be of more relevance in early neuropathy. Long term double-blind multicentre trials are in progress, and preliminary data from some of these are reasonably encouraging. In conclusion, the results from clinical trials of the aldose reductase inhibitors in this difficult area are sufficiently encouraging to lead us to be optimistic about their future development, and continuing work should clarify their potential role with respect to the prophylaxis and treatment of diabetic neuropathy. PMID- 2109680 TI - [Valpromide-amitriptyline interaction. Increase in the bioavailability of amitriptyline and nortriptyline caused by valpromide]. AB - Valpromide is largely used in the therapy of affective disorders for its presumed thymoregulating activity. So, it is often associated with tricyclic antidepressant treatment. Previous clinical studies lead us to consider the possibility of an interaction between valpromide and tricyclic antidepressants, interaction which could result in an increase of antidepressant plasma concentrations. But no pharmacokinetic study has been realized up to now in order to clearly demonstrate such a phenomenon. The authors studied amitriptyline and nortriptyline plasma levels in two groups of ten patients receiving 125 mg amitriptyline, once a day, during 20 days. In the second group, patients also received 600 mg valpromide daily after ten days on amitriptyline. In the first group amitriptyline and nortriptyline plasma concentrations remained stable between the tenth and the twentieth day. In the second group, addition of valpromide resulted in a significant increase of antidepressant plasma levels: from 70.5 +/- 35 to 105.5 +/- 49 ng/ml (p less than 0.0003) for amitriptyline, and from 61.0 +/- 34 to 100.5 +/- 65 ng/ml (p less than 0.01) for nortriptyline. PMID- 2109681 TI - Secretion of plasminogen activator from bovine parathyroid cells. AB - The characteristics and secretion of plasminogen activator (PA) were examined in fresh and cultured bovine parathyroid cells. Release of PA activity was maximal at low Ca concentrations ([Ca]) and suppressed at physiological [Ca]. PA secretion at high [Ca], like that of PTH, was increased by treatment of cells with chloroquine and/or 3-methyladenine. Secretion from organoids was not affected by hydrocortisone hemisuccinate, but was strongly increased by 1,25 dihydroxyvitamin D3. In cell homogenates, PA specific activity was highest in microsomes, from which less than 50% could be solubilized by Triton X-100. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of microsomes and media followed by zymography on fibrin-agarose gels showed that PA from both sources had an apparent mol wt of 44,000. No inhibitors of PA were detected by reverse zymography. PA activity was inhibited by placental urokinase (uPA) inhibitor and amiloride, which indicated that it was a uPA, but the secreted form required tissue-type PA stimulator (fibrin peptides) or denatured microsomes for full activity. Neither the microsomal nor the secreted forms of PA were active with S 2444, a substrate specific for active uPA. By comparison with the characteristics of human activators, the results suggested that parathyroid cells secrete uPA that is primarily in the precursor form single chain urokinase or scuPA. PMID- 2109682 TI - Effects of progesterone on the estradiol-induced follicle-stimulating hormone (FSH) surge and FSH beta messenger ribonucleic acid in the rat. AB - This study was designed to investigate the effects of progesterone on the estradiol (E2)-induced FSH surge and FSH beta messenger RNA (mRNA) using immature rat models developed previously to demonstrate inhibition or facilitation of the LH surge by progesterone. Twenty-eight day-old rats that received E2 implants at 0900 h had FSH surges about 1700 h on day 29 (32 h). In rats treated with E2 alone, serum FSH was 15.1 +/- 1.6 ng/ml at this time, while in those animals treated concurrently with E2 and progesterone, serum FSH was significantly suppressed (8.3 +/- 0.7 ng/ml, P less than 0.001). For demonstration of progesterone facilitation, rats were primed for 24 h with E2 before progesterone treatment. This led to premature and enhanced FSH secretion: at 1400 h on day 29 serum FSH was 45.5 +/- 2.7 ng/ml compared to 6.4 +/- 0.5 ng/ml in rats treated with E2 alone. To examine the effects of these dual actions of progesterone on FSH synthesis, steady state concentrations of FSH beta mRNA were measured by Northern analysis. FSH beta mRNA generally increased in parallel with FSH release. Levels of this mRNA were about 1.5-fold higher in rats undergoing E2 induced FSH surges than in rats in which the surge was blocked by progesterone. Also, at the onset of the progesterone-facilitated FSH surge, FSH beta mRNA was about 5-fold higher in animals treated with E2 and progesterone than in those treated with E2 only. On the morning after the FSH surge (48 h after E2 treatment) FSH beta mRNA was low to undetectable. In contrast, levels of FSH beta mRNA were 7- to 8-fold higher at this time in rats in which the surge was blocked by progesterone. Serum inhibin concentrations were significantly elevated (P less than 0.05) in animals treated with E2 alone for 32 h (3077 +/- 260 fmol/ml) or 48 h (2344 +/- 148 fmol/ml) compared to those treated with E2 and progesterone in the inhibition paradigm (2469 +/- 106, 1896 +/- 114 fmol/ml, respectively). After 32 h of E2 treatment in the facilitation paradigm, serum inhibin was comparable (P greater than 0.2) in rats treated for 8 h with blank implants (2592 +/- 168 fmol/ml) and those treated for 8 h with progesterone (2720 +/- 188 fmol/ml).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2109679 TI - Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile. AB - The gonadotrophin releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); gonadorelin] agonist buserelin is a promising new agent in the treatment of a variety of disorders in gynaecology and andrology, paediatrics and oncology. While a single dose of buserelin stimulates the release of pituitary gonadotrophins, multiple doses produce reversible pituitary desensitisation, and this specific blockade of gonadotrophin support to the gonads provides the basis for the drug's efficacy in conditions dependent on sex hormone secretion. Thus, buserelin provides comparable efficacy to orchidectomy or high dose estrogens in the treatment of hormone-sensitive prostate cancer and exhibits a lower incidence of adverse effects. During the early phase of treatment it may be particularly useful in combination with antiandrogens. Buserelin also appears promising in hormone-sensitive premenopausal breast cancer. Extensive studies have proven the value of buserelin in endometriosis, where it produces a transient remission with gradual recurrence of the disease on cessation of treatment. Surgical intervention is necessary in severe disease after buserelin-induced involution of the lesions. In patients with uterine leiomyoma, preliminary data suggest that buserelin may be beneficial in rendering surgery more conservative by reducing fibroid size, although it appears unlikely to preclude surgical intervention. The use of buserelin to induce a state of reversible hypogonadotrophism before administration of exogenous gonadotrophins is a promising strategy in the treatment of infertility associated with polycystic ovary syndrome and other conditions of infertility with underlying ovarian dysfunction; such a strategy also clearly enhances the efficiency of in vitro fertilisation programmes. Initial studies suggest its potential usefulness as a female contraceptive when administered intermittently in conjunction with a progestogen. Buserelin represents a first-line treatment of central precocious puberty. In endometriosis the adverse effect profile of buserelin is generally favourable, with hypoestrogenic effects such as hot flushes and vaginal dryness, and decreased libido, predominating. There is no apparent detrimental effect on lipid metabolism. The potential for adverse hypoestrogenic effects on bone mineral content with long term administration remains to be clarified. Thus, the GnRH agonist buserelin represents an advance in the treatment of a variety of gynaecological and andrological as well as paediatric and oncological conditions, infertility and other sex-hormone dependent conditions, with a low incidence of adverse treatment effects. PMID- 2109683 TI - Gonadotropin induction of c-fos and c-myc expression and deoxyribonucleic acid synthesis in rat granulosa cells. AB - Although gonadotropins stimulate ovarian granulosa cells to proliferate and differentiate into steroidogenic cells, little is known about the molecular mechanisms by which gonadotropins induce these fundamentally different responses. In this study the acute effects of PMSG on protooncogene expression, DNA synthesis, and steroid secretion were examined. The levels of c-fos, c-myc, and beta-actin mRNA were measured in total RNA samples from granulosa cells by quantitative polymerase chain reaction. PMSG increased the mRNA levels of c-fos, c-myc, and beta-actin within 15 min. Fos and myc proteins were localized within granulosa cells by immunocytochemistry. Less than 10% of granulosa cells stained for c-fos or c-myc proteins in the control samples. In contrast, approximately 40% of the cells stained for these protooncogene proteins 30 min after PMSG injection (P less than 0.05). These values declined to about 10% of the cells 60 min after PMSG injection. DNA synthesis, as estimated by [3H]thymidine incorporation, increased 30 and 60 min after PMSG (P less than 0.05). 17 beta Estradiol and progesterone synthesis did not change within 60 min of PMSG injection. These data demonstrate that 1) c-fos and c-myc are expressed in ovarian granulosa cells; 2) the expression of the genes encoding c-fos, c-myc, and beta-actin is rapidly increased by gonadotropin; and 3) the increase in the corresponding products of the c-fos and the c-myc genes precedes an increase in DNA synthesis and steroid production. These data suggest that the expression of c fos and c-myc may be a part of the molecular mechanism through which gonadotropins regulate granulosa cell function. PMID- 2109684 TI - Direct neuropeptide Y-induced modulation of gonadotrope intracellular calcium transients and gonadotropin secretion. AB - Neuropeptide Y (NPY) has been shown to be capable of both the enhancement and suppression of gonadotropin secretion from pituitary cells. In order to elucidate the underlying cellular mechanisms which might account for these actions, we have examined the effects of NPY on gonadotropin secretion stimulated by either cell depolarization or by GnRH from primary cultures of rat pituitary cells. In one set of experiments, we measured single-cell [Ca2+]i using the Ca2(+)-sensitive intracellular fluorescent indicator Fura-2, in gonadotropes which had been identified using a reverse hemolytic plaque assay employing an antiserum to LH. In another group of investigations, we measured FSH and LH secretion in response to depolarization or stimulation with GnRH, and examined the influence of NPY on these patterns of secretion. NPY was active in inhibiting the amplitude of the [Ca2+]i signal induced by depolarization with 20 mM K+, as well as in substantially blocking the secondary plateau phase of the GnRH-induced elevation of [Ca2+]i. However, the peak [Ca2+]i transients occurring in response to either depolarization with 50 mM K+ or the initial phase of the GnRH-induced response, were not sensitive to blockade by NPY. Moreover, treatment of the cells for 24 h with pertussis toxin prevented the NPY-mediated inhibition of the GnRH-stimulated [Ca2+]i plateau. Cell depolarization by 50 mM K+ induced 3-fold increases in FSH and LH release over 2-h incubations. GnRH (100 nM) elicited a 9-fold increase in FSH and a 14-fold stimulation of LH over the same time period. NPY had insignificant effects upon depolarization-induced hormone release, but at 1 microM partially suppressed LH release elicited by 100 nM GnRH over 2 h. We conclude that NPY is capable of inhibiting [Ca2+]i signals in gonadotropes that are stimulated by GnRH, and that these effects are mediated through activation of a pertussis toxin-sensitive G-protein. These effects on [Ca2+]i may underly the inhibitory effects of NPY on gonadotropin secretion. PMID- 2109685 TI - cis-platinum-mediated decrease in serum testosterone is associated with depression of luteinizing hormone receptors and cytochrome P-450scc in rat testis. AB - Previously we had shown that cis-platinum decreases testosterone levels in rat serum and that hCG reverses this effect. The purpose of these studies was to determine the biochemical basis of cis-platinum-mediated effects on testicular testosterone production. In the testis of rats treated with cis-platinum (7 mg/kg, iv), the mitochondrial P-450scc concentration and side-chain cleavage activity were depressed by 40%. Also, the microsomal 17 alpha-hydroxylase activity and cytochrome P-450 concentration were decreased. Testicular binding capacity (in vitro) for [125I]hCG was decreased by 75-80%. On the other hand, FSH binding to Sertoli cell membrane receptors was not appreciably changed. hCG (25 IU/100 g daily) in treated rats caused complete occupancy of the remaining 20-25% LH receptors and caused a 20- to 30-fold increase in serum and testicular testosterone, a 2-fold increase in mitochondrial P-450scc, and a 5-fold acceleration of side-chain cleavage activity. 17 alpha-Hydroxylase activity and microsomal cytochrome P-450 were not increased over the control values. In addition to testicular functions, pituitary glycoprotein hormone production was assessed. Treatment of rats with cis-platinum (7 mg/kg, iv) did not change serum LH or FSH, but caused a 50% decrease in serum and testicular testosterone levels. A GnRH challenge test (1.5 micrograms/100 g, in 30 min) of treated rats caused prompt increases of 10- to 15-fold in serum LH and resulted in increases in serum and testicular testosterone. Thus, there was little evidence for cis-platinum effects at the level of hypothalamus or pituitary that could account for the decreased testosterone production. Reversal of the cis-platinum effect on steroidogenesis by hCG or GnRH appears to be due to the induction of suprasaturating levels of LH with full occupancy of remaining Leydig cell LH receptors. This, in turn, would reverse the diminished levels of mitochondrial side-chain cleavage activity and cytochrome P-450scc. These data suggest that cis platinum causes a depression in serum testosterone, mainly by decreasing the number of LH receptors and inhibiting side-chain cleavage activity. PMID- 2109686 TI - Glyburide increases insulin sensitivity and responsiveness in peripheral tissues of the rat as determined by the glucose clamp technique. AB - The effect of chronic glyburide treatment on insulin sensitivity and responsiveness in vivo in unanesthetized male Sprague-Dawley rats was determined by the hyperinsulinemic-euglycemic clamp technique. Normal animals were surgically prepared for the clamp procedure and then gavaged with glyburide, 2 mg/kg/day, or with normal saline for 6-18 days. Basal plasma glucose concentrations were significantly lower in glyburide-treated animals compared to controls, but basal plasma insulin concentrations were the same. Rates of glucose disposal, calculated before and during insulin infusions of 2 to 40 mU/kg.min with plasma glucose concentration clamped at 125 mg/dl, were significantly greater in the glyburide-treated rats compared to controls. Insulin dose-response curves demonstrate that glyburide treatment increased both insulin sensitivity and responsiveness. Basal hepatic glucose production, estimated by D-[3 3H]Glucose infusion, was significantly greater with glyburide treatment; however the sensitivity of the liver to suppression by insulin infusions of 2 and 4 mU/kg.min was unchanged. These data suggest that the decreased basal plasma glucose concentration observed in rats chronically treated with glyburide is the result of increased glucose disposal in peripheral tissues and not associated with an increase in plasma insulin concentrations or a decrease in hepatic glucose production. PMID- 2109687 TI - Neuropeptide-Y-immunoreactive innervation of thyrotropin-releasing hormone synthesizing neurons in the rat hypothalamic paraventricular nucleus. AB - The association of neuropeptide-Y (NPY)-immunoreactive (IR) axon terminals with TRH-synthesizing neurons in the rat hypothalamic paraventricular nucleus (PVN) has been studied. Immunocytochemical single and double labeling studies were performed at both light and electron microscopic levels using antiserum to NPY and, as a marker of TRH-containing neurons, antisera recognizing the N-terminal flanking peptides of the TRH prohormone, prepro-TRH-(25-50) and prepro-TRH-(53 74). At the light microscopic level, a diffuse group of TRH-IR cell bodies were observed in the anterior parvocellular subdivision of the PVN and became more numerous and densely clustered in the medial and periventricular parvocellular subdivisions. NPY-IR fibers were observed to innervate all subdivisions of the PVN, but were particularly dense in the anterior, medial, and periventricular parvocellular subdivisions of the nucleus, where they appeared to contact TRH synthesizing perikarya and neuronal processes. At the ultrastructural level, numerous NPY-IR axon terminals containing labeled vesicles were either tightly juxtaposed to TRH-producing neurons or seen to establish both symmetric and asymmetric synaptic contacts with TRH-containing cell bodies and dendrites. Some NPY-IR axon terminals also established synaptic contacts with unlabeled PVN perikarya and processes or were found in close apposition to blood vessels. These data provide a morphological basis to suggest NPY-mediated neuroendocrine regulation over the biosynthesis and/or secretion of TRH in the PVN. Reports of the colocalization of NPY and catecholamines in the same axon terminals raises the possibility of a potential interaction between NPY and catecholamines to influence TRH neurons in the PVN. Morphological evidence for synaptic interactions between NPY-IR axon terminals and non-TRH-containing neurons in the PVN further suggests that this peptide may influence other neuroendocrine systems. PMID- 2109688 TI - Evidence for high molecular weight immunoreactive thyrotropin-releasing hormone (TRH) precursor forms in the developing mouse hypothalamus. Simultaneous immunolocalization with TRH in cultured neurons. AB - Two antisera (Anti-P7 and Anti-P10) were raised against (-Gln-His-Pro-Gly-) elongated peptides: P7 Gln-His-Pro-Gly-Lys-Arg-Phe) and P10 (Ser-Lys-Arg-Gln-His Pro-Gly-Lys-Arg-Phe). They recognized TRH extended peptides but not TRH. A RIA against P7 and a highly sensitive enzyme immunoassay against P10 were used to identify two major high mol wt forms of 25-35 K and 6-8 K in chromatography fractions of adult and fetal mouse as well as adult rat hypothalami. The existence of the largest form was confirmed by immunoblotting with Anti-P7. During mouse hypothalamus development in vivo and in vitro, the ratio of TRH content vs. P10-associated immunoreactivity increased several times. This suggests that these Pro-TRH peptides are precursors of TRH biosynthesis and indicate an acceleration of TRH processing during development. Double immunostaining with A-TRH and A-P7 of hypothalamic cells taken on the 16th fetal day and cultured for 6, 12, and 18 days in vitro (DIV) revealed three populations of neurons: 1) a very minor population (approximately 2%) of small round cells positive with A-TRH only; 2) a major population of neurons positive with both A TRH and A-P7. 3) multipolar neurons positive with A-P7 only (up to approximately 45% after 18 DIV). The respective distribution of TRH and P7 along neurites also varied with time in culture. Whatever perikarya staining, TRH was restricted to short neurites and growth cones before synapse formation and, during synapse development, to varicosities and terminal boutons. However even at the latest stage examined some varicosities and terminal boutons were positive with A-P7 only. These results suggest a preferential processing of pro-TRH at a post-Golgi step during axonal transport to growth cones and synaptic boutons. PMID- 2109689 TI - Urokinase-type plasminogen activator is increased in the involuting ventral prostate of castrated rats. AB - We have investigated the content of plasminogen activators in the rat ventral prostate during castration. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and zymography demonstrated two major Mr-forms of plasminogen activators that were found to be strongly increased by castration; inclusion of quenching antibodies in the zymography and immunoblotting analysis identified these as urokinase-type plasminogen activator (u-PA) and its Mr 30,000 degradation product, respectively. A third, less abundant form, which was identified as tissue-type plasminogen activator, was also increased by castration. The induction of the plasminogen activators was prevented by treating the rats with 5 alpha-dihydrotestosterone. The increase in u-PA antigen was quantitated by the use of enzyme-linked immunosorbent assay. The increases in u PA activity and antigen were traced back to a corresponding increase in u-PA messenger RNA (mRNA). By immunohistochemical methods, the u-PA was found to be present in scattered single cells at the surface of the epithelium facing the lumen of the glandular ducts. Such cells were present in control as well as in castrated rats, but their number increased after castration. In addition, after castration, u-PA immunoreactivity appeared in cells throughout the epithelium. These results suggest a role for plasminogen activation in castration-induced involution of the rat ventral prostate, and a role in the normal turnover of the rat ventral prostate epithelium. PMID- 2109691 TI - Cognitive effects of valproate. AB - The effects of valproate on cognition are usually considered to be minimal, but few formal neuropsychological studies are available. We studied the psychomotor performances of 20 seizure-free epileptics during fixed valproate monotherapy and after its withdrawal. Our findings suggest some adverse effects of valproate which appear to be completely reversible after withdrawal. PMID- 2109690 TI - Effects of tumor necrosis factor-alpha in vitro on steroidogenesis of healthy and atretic follicles of the rat: theca as a target. AB - Tumor necrosis factor-alpha (TNF), a pleiotropic cytokine localized within the ovary, alters follicular steroidogenesis. Preovulatory follicles dissected from ovaries of normal cyclic adult rats on the morning of proestrus exhibit steroidogenic and histological signs of atresia after 24 h of culture under the conditions of 5% CO2 and air. Follicles cultured for 24 h in 5% CO2 and 95% O2 appeared histologically and steroidogenically healthy. Under both culture conditions, human recombinant TNF (5 ng/ml) significantly increased the production of pregnenolone, progesterone, 20 alpha-dihydroprogesterone, and 17 alpha-hydroxyprogesterone by the follicles. Follicles cultured in 5% CO2 and air exhibited no change in androstenedione or estradiol production compared to control follicles incubated without TNF. In contrast, follicles cultured in 5% CO2 and 95% O2 responded to TNF with increased androstenedione and estradiol production. Separation of the thecal and granulosa compartments indicated that the increased progestin production observed in the whole follicle in response to TNF originated from the theca. TNF significantly inhibited basal and FSH stimulated progesterone production from the granulosa of preovulatory follicles. Exogenous substrate added to whole follicles cultured in the presence or absence of TNF indicated that TNF enhanced the conversion of 25-hydroxycholesterol to pregnenolone. These studies reveal that TNF enhanced steroidogenesis in both healthy and atretic follicles and that this action of TNF is on the theca, where TNF increases the conversion of cholesterol to pregnenolone. The data imply that TNF has differential effects on thecal and granulosa steroidogenesis. PMID- 2109692 TI - Catecholaminergic systems and amygdala kindling development. Effects of bilateral lesions of substantia nigra dopaminergic or locus coeruleus noradrenergic neurones. AB - The effects of the bilateral and selective destruction of substantia nigra (SN) dopaminergic or locus coeruleus (LC) noradrenergic neurones, consecutive to a local injection of 6-hydroxydopamine, were studied on the development of amygdala kindling. Immunohistochemical controls of lesions were performed using selective dopamine (DA) or norepinephrine (NE) antibodies. The results demonstrated that a massive destruction of SN pars compacta neurones did not modify the rate of kindling development. Conversely, the lesions of LC neurones (sparing lateral tegmental nuclei) markedly facilitated the development of amygdala kindling. This effect was related to the extent of NE denervation. Together, these results suggest that DA is not strongly involved in the development of kindling, and that the nigrostriatal output does not play a major role in the generalization of kindled seizures. In contrast, they confirm an inhibitory influence exerted by LC noradrenergic ascending pathways on the development of kindling. PMID- 2109693 TI - Truncation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) from Rhodospirillum rubrum affects the holoenzyme assembly and activity. AB - Truncations of the subunit of ribulose bisphosphate carboxylase/oxygenase (Rubisco) from Rhodospirillum rubrum were generated by site-directed mutagenesis to examine the role of the C-terminal tail section. Removal of the last and the penultimate alpha-helices in the tail section changes the quaternary structure of the protein. Electrophoretic and electron microscope analysis revealed that the truncated subunits assemble into an octamer, whereas the wild-type enzyme has a dimeric structure. The octomerization of the mutant protein is due to a hydrophobic patch exposed to the solvent by truncation of the subunit. The mutant protein thus consists of four dimers, bound end-to-end by hydrophobic interactions. Insertion of a polar amino acid in the hydrophobic patch by a L424 to N424 substitution restores the familiar dimeric structure. Truncation of the subunit is associated with a considerable decrease in catalytic activity. The mutants undergo carbamylation but bind the reaction intermediate analog, 2 carboxy arabinitol-1,5-bisphosphate, poorly. This indicates that loss of activity in the mutant is due to weakened substrate binding. These findings suggest that the mutations in the tail section of the subunit are transmitted to the active site, although the C-terminal region is far from the active site. On the basis of the crystal structure of Rubisco, we propose a model for how the truncations of the enzyme subunit induce conformational changes in one of the two phosphate binding sites. PMID- 2109694 TI - A Go-like protein in Drosophila melanogaster and its expression in memory mutants. AB - G proteins couple receptors for extracellular signals to several intracellular effector systems and play a key role in signalling transduction mechanisms. In particulate preparations of Drosophila melanogaster heads, only one substrate for pertussis toxin at 39-40 kd was detected. This substrate, which showed only one isoform when analysed by isoelectric focusing, was recognized by immunoblotting and immunoprecipitation techniques using a polyclonal antibody against the alpha subunit of the Go protein purified from bovine brain and can be thus considered as a Go-like protein. Antibodies obtained against a carboxy-terminal sequence of the alpha subunit of Go (but not of Gi1 or Gi2) and against an internal sequence shared by all the alpha subunits, were also able to cross-react with the alpha subunit of this protein in insects. We have also studied the Go-like protein in several D.melanogaster mutants, primarily in memory and learning mutants. In these mutants there was a sex-dependent enhancement in pertussis toxin-catalysed ADP-ribosylation with respect to the wild-type. This increase could be attributed in part to an increase in the alpha subunit of the Go-like protein, as revealed by immunoblotting with anti-Go alpha polyclonal antibody. This report constitutes the first evidence for the participation of a Go protein in learning and memory. PMID- 2109695 TI - Functional dissection of an early Drosophila chorion gene promoter: expression throughout the follicular epithelium is under spatially composite regulation. AB - We have fused various DNA sequences located upstream of the Drosophila melanogaster s36 chorion gene TATA box to a heterologous basal promoter and reporter gene (hsp70/lacZ). The expression of these constructs, following P element-mediated germline transformation, was examined in 144 independent lines by histological staining of dissected ovaries for beta-galactosidase activity. A short 84 bp segment of the proximal 5' flanking DNA was sufficient to confer a wild-type gene expression pattern, including temporal specificity for early choriogenic follicles. Surprisingly, initial expression was very localized at the anterior and posterior poles of the follicle. The downstream half of that DNA segment permitted expression at both poles, but especially at the anterior tip, while the upstream half only favored expression in the posterior pole; these results suggested the existence of multiple, spatially specific cis-regulatory elements. When the proximal 84 bp segment was placed 1.5 kb upstream of the basal promoter, beta-galactosidase activity was observed in an altered spatial pattern, indicating that the cis-regulatory element(s) that favor expression in the posterior half of the follicle are position independent, while the element(s) that favor expression elsewhere in the follicle are position sensitive. A distal regulatory segment containing redundant DNA element(s) specific for expression in the anterior pole was identified much further upstream of s36. Thus, the expression of this chorion gene throughout the follicular epithelium is actually composite, occurring in distinct spatial domains under the control of corresponding DNA elements. PMID- 2109696 TI - Transposition of human immunoglobulin V kappa genes within the same chromosome and the mechanism of their amplification. AB - The variable, joining and constant gene segments of the human immunoglobulin kappa locus (V kappa, J kappa and C kappa) are located on the short arm of chromosome 2 at 2p11-2p12. Here we describe a cluster of 11 V kappa genes on the long arm of chromosome 2 at 2cen-q11. By pulsed-field gel electrophoresis, cosmid cloning and DNA sequencing the cluster was shown to consist of four amplified units (amplicons). The amplicons, each 110-160 kb in size, are organized within 650 kb as an array of inverted repeats with short stretches of non-amplified DNA in between. Cloning and sequencing of three different joints between amplified and non-amplified DNA revealed the existence of parts of Alu repeats at each of the analysed joints. It is suggested that during evolution a group of five V kappa genes was transposed from the short to the long arm of chromosome 2 by a pericentric inversion. Three of the five V kappa genes were then amplified in two subsequent steps to yield the structure found in the majority of the present day population. The possible relation of this structure to a pericentric inversion of chromosome 2 that is seen cytogenetically in a small fraction of today's population is discussed. PMID- 2109697 TI - Immunocytochemical localization of sphingolipid activator protein 2 (SAP-2) in normal and SAP-deficient fibroblasts. AB - The intracellular localization of sphingolipid activator protein 2 (SAP-2) was determined immunocytochemically using an antiserum raised against a SAP-2 preparation from Gaucher spleen. The immunolabeling indicated that SAP-2 was largely localized in the lysosomes of fibroblasts from normal individuals. In some lysosomes the labeling was greatest around the perimeter of the matrix, suggesting an association between the activator and lysosomal membrane components. The labeling technique was also applied to fibroblasts from a patient with a unique sphingolipid storage disorder. Consistent with immunoblotting studies on electrophoretograms, both the patient and his affected fetal sibling were found to be deficient in immunoreactive SAP-2. PMID- 2109698 TI - Spindles and centrosomes during male meiosis in Drosophila melanogaster. AB - We have studied the spatial distribution of chromosomes, spindle fibers and centrosomes throughout the first meiotic division in males of Drosophila melanogaster. There seem to be two different types of spindle fibers: those which connect the poles to the chromosomes, and others arranged as cup-shaped hemispheres that reach from the poles to an unstained area on the equator of the cell. These pole-equator fibers could be responsible for positioning the nucleus and distributing cytoplasmic organelles around the nucleus during prophase, so that after meiosis, the daughter cells are provided with equal amounts of preorganized cytoplasmic organelles. These fibers remain until after the daughter nuclei have formed during telophase. An antigen associated with the centrosomes of mitotic spindles appears during meiosis as dispersed particles surrounding the nucleus; these particles might provide the developing spermatids with microtubule organizing centers. PMID- 2109699 TI - Lack of interference by sorbitol with aminopyrine breath test. AB - The effect of sorbitol on the aminopyrine breath test was investigated in 13 patients with various liver diseases given a bolus dose of sorbitol 20 mg.kg-1 i.v. 30 min after 14C-aminopyrine and 13 patients without the sorbitol bolus who also underwent an aminopyrine breath test. The time course of 14CO2 exhalation after the bolus of sorbitol did not differ from that in the control group. PMID- 2109700 TI - Possible protein binding displacement interaction between glibenclamide and metolazone. AB - The effects of metolazone on the protein binding of glibenclamide were studied. It was found that increasing metolazone concentrations up to 100 ng/ml had no significant effect on the protein binding of glibenclamide studied at 10 micrograms/ml. Metolazone is unlikely to cause a clinically significant increase in the free fraction of glibenclamide in patients receiving both drugs. PMID- 2109701 TI - Induction of aldose reductase expression in rat kidney mesangial cells and Chinese hamster ovary cells under hypertonic conditions. AB - Rat kidney cortex mesangial cells (MES) and Chinese hamster ovary cells (CHO) responded to hypertonicity (600 mosmol/kg) in culture by accumulating sorbitol. The accumulation of sorbitol was due to increased aldose reductase (AR) activity, apparently brought about by increased levels of AR mRNA and protein. The levels of AR mRNA increased approximately 60-fold in MES cells and 30-fold in CHO cells by 24 h in culture media (300 mosmol/kg supplemented with 150 mM NaCl, 600 mosmol/kg total). AR activity also markedly increased (14- to 16-fold above control), but MES took 4 days and CHO 6 days to reach this maximum. Other osmolytes, raffinose and sorbitol (at concentrations of 250 to 300 mM) elicited the same response as that of 150 mM NaCl. These data show that AR expression is induced in MES and CHO cells under hypertonic conditions. Of special interest is the induction of large amounts of AR in rat kidney cortex mesangial cells, a target tissue of diabetes and a site where excessive accumulation of sorbitol is suspected to be a critical factor in diabetic nephropathy. PMID- 2109702 TI - Expression of c-myc gene in human ovary carcinoma cells treated with vanadate. AB - The widely accepted hypothesis of vanadate action on cells postulates that this ion inhibits protein phosphatase(s) that dephosphorylates protein phosphotyrosine residues. This inhibition causes tyrosine hyperphosphorylation of cell proteins followed by changes in physiological action of phosphoproteins resulting in stimulation of cell proliferation, expression of protooncogenes, and transient cell transformation. We have found that treatment of human ovary carcinoma (CaOv) cells with vanadate causes the increase in total protein phosphorylation from 1.5 to 2.0-fold whereas the ratio between phosphoserine, phosphothreonine, and phosphotyrosine content remains unchanged. At the same time, enhancement of c-myc gene expression (not c-fos) was observed. Hence, the increase in the ratio of phosphotyrosine to phosphoserine and phosphothreonine is not an obligatory intermediate stage before vanadate-dependent activation of c-myc expression. PMID- 2109703 TI - Correlation between neopterin, interferon-gamma and haemoglobin in patients with haematological disorders. AB - In this study, we further investigated a possible link between activation of cell mediated immunity and anaemia in patients with haematological neoplasias. We compared serum concentrations of interferon-gamma and neopterin with haemoglobin levels. Significantly increased interferon-gamma and neopterin concentrations indicated persistent activation of cell-mediated immunity. Neopterin levels correlated significantly to interferon-gamma concentrations and inversely to haemoglobin levels. The data indicate an association between activated macrophages and the development of anaemia in patients with haematological neoplasias. PMID- 2109704 TI - [An electrophysiological analysis of the action of an antioxidant of the 3 hydroxypyridine class on the cerebral epileptic activity in rats with a cobalt induced focus]. AB - In experiments on albino male rats with chronically implanted electrodes and an epileptogenic focus in the cortical sensomotor region it was shown that a derivative of 3-hydroxy-pyridine (2-ethyl-6-methyl-3-hydroxypyridine) possesses the pronounced antiepileptic effect. The effect of the agent is related to the functional state of the epileptic system whose resistance to pharmacotherapy depends on the power of the determinant focus. PMID- 2109705 TI - [The mechanism of the antianginal action of nitroglycerin]. PMID- 2109706 TI - A comparative study of drug metabolizing enzymes in adrenal glands and livers of rats and chickens. AB - 1. Drug metabolizing enzymes (cytochrome P450, glutathione-S-transferase, carboxylesterase) were compared in livers and adrenal glands from rats and chickens. 2. Quantities of cytochrome P450 in chicken liver and adrenal glands were less than in rat liver and adrenals. 3. Activities of carboxylesterase and of glutathione-S-epoxide transferase were similar in livers of rats and chickens. 4. In the chicken, activities of carboxylesterase and of glutathione-S-epoxide transferase were less in adrenal glands than in livers. 5. Carboxylesterase enzyme activities in adrenal glands of chickens were more sensitive to inhibition by antiesterase agents than were carboxylesterase enzyme activities in liver. PMID- 2109707 TI - Pertussis toxin-mediated ADP-ribosylation of rabbit luteal Gi uncouples enkephalin inhibition of adenylyl cyclase. AB - 1. Some of the actions of pertussis toxin on the rabbit luteal adenylyl cyclase system were analyzed. 2. Incubation of luteal membranes with pertussis toxin and [32P]NAD resulted in the [32P]ADP-ribosylation of a 40,000 Da protein that is distinct from the proteins ADP-ribosylated by cholera toxin. 3. Pertussis toxin specific [32P]ADP-ribosylation was time-dependent and dependent upon the concentration of pertussis toxin present during the incubation. 4. Pertussis toxin mediated [32P]ADP-ribosylation was enhanced by ATP, ADP, adenylyl imidodiphosphate, GTP, guanosine-5'-O-(2-thiodiphosphate), guanosine-5'-O-(3 thiotriphosphate), and NaF but not AMP or guanylyl imidodiphosphate [GMP-P(NH)P]. 5. Treatment of luteal membranes with NAD and pertussis toxin prevents GTP and enkephalin but not GMP-P(NH)P mediated inhibition of forskolin stimulated adenylyl cyclase, demonstrating the existence of a functional Gi in the rabbit corpus luteum. PMID- 2109708 TI - Hepatic bilirubin and UDP-glucuronate levels in Bolivian squirrel monkeys exhibiting fasting hyperbilirubinemia. AB - 1. Bolivian squirrel monkeys (BoSMs), which are animal models for Gilbert's syndrome, have 40% less hepatic bilirubin UDP-glucuronyltransferase (BR-UPPG-T) activity than Brazilian squirrel monkeys (BrSMs). 2. Although fasting results in similar decreases in hepatic UDP-glucose and UDP-glucuronate levels in both simian subspecies, increased activities (55%) of BR-UDPG-T are induced only in the fasted control BrSMs, which do not exhibit the marked fasting hyperbilirubinemia (FH). 3. Total hepatic bilirubin (BR) concentrations were 50% greater in both fed and fasted BoSMs when compared to BrSMs. 4. Hepatic unconjugated BR levels increase upon fasting only in Gilbert-like BoSMs, reaching concentrations twice that observed in BrSMs. 5. Elevated hepatic BR levels in fasted BoSMs may reflect BR overproduction or inadequate glucuronidation. 6. The increased BR-UDPG-T activity induced in BrSMs during fasting could compensate in part for the UDPGA depletion and prevent the marked FH as observed in BoSMs. PMID- 2109709 TI - Inhibin. PMID- 2109710 TI - Mechanism of action of gonadotropin releasing hormone upon gonadotropin secretion: involvement of protein kinase C as revealed by staurosporine inhibition and enzyme depletion. AB - The role of protein kinase C (PKC) in the mechanism of action of gonadotropin releasing hormone (GnRH) upon gonadotropin secretion is controversial and therefore was investigated in primary cultures of rat anterior pituitary cells. A relatively selective PKC inhibitor, staurosporine, inhibited both GnRH- and 12-O tetradecanoylphorbol 13-acetate (TPA)-induced luteinizing hormone (LH) release with half-maximal inhibition (IC50) of about 80 nM. Inhibition of GnRH action was not complete suggesting also a PKC-insensitive component in GnRH-induced gonadotropin release. Staurosporine had no effect on basal LH release, or on cellular LH content, neither did the drug interfere with the binding of [125I]iodo-[D-Ser(t-Bu)6]des-Gly10-GnRH N-ethylamide to its receptor in pituitary cells. When cultured pituitary cells were incubated with TPA (1 microM) for 24-48 h no measurable cellular PKC activity could be detected. The decrease in total PKC activity was accompanied by an increase in Ca2+, phosphatidylserine (PS), diacylglycerol (DG)-insensitive activity suggesting the release of a portion of the catalytic domain of PKC (M-kinase) by the phorbol ester treatment. TPA induced LH release was nearly abolished in PKC-depleted cells and the response to GnRH was markedly reduced (40%). The stimulatory effect of the Ca2+ ionophore, ionomycin, was not impaired in PKC-depleted cells. Impaired responses to GnRH in PKC-depleted cells were only noticed at a later phase (2-4 h) of the exocytotic response of the neurohormone. The data strongly suggest a role for PKC during the second phase of GnRH-induced gonadotropin secretion. PMID- 2109711 TI - Activin A increases the number of follicle-stimulating hormone cells in anterior pituitary cultures. AB - The mode of action of activin A on the anterior pituitary gland (AP) was investigated using primary cultured cells. The AP cells were cultured with activin A (1 ng/ml) at various cell densities for 24-96 h, and further incubated for 3 h with activin A-free medium. When the cells were pretreated with activin A for 48 h, follicle-stimulating hormone (FSH) secretion during the following 3-h incubation was increased only at a density of 1 x 10(5) cells/200 mm2, but not at 2 x 10(5) or 4 x 10(5) cells/200 mm2. A longer pretreatment (96 h) was required in order to induce this response at a density of 2 x 10(5) cells/200 mm2. Luteinizing hormone (LH) secretion was not affected by activin A. Thus, the FSH secretory activity of the primary culture of AP was stimulated by activin A in a cell density-dependent manner. Furthermore, it was found that treatment with activin A (10 ng/ml) for 72 h increased the number of immunoreactive FSH cells by 25-41%, and that these newly induced FSH cells were low responders to gonadotropin-releasing hormone stimulation. The proportions of immunoreactive LH, thyroid-stimulating hormone, prolactin or growth hormone cells were not affected. From these results, we conclude that activin A increases FSH secretion by changing the cell population of pituitary gonadotropes. PMID- 2109712 TI - Structure, cell-specific expression, and mating-induced regulation of a Drosophila melanogaster male accessory gland gene. AB - The accessory gland of male insects is a secretory tissue of the genital tract made up of several distinct cell types. It secretes components of the ejaculatory fluid which have an important effect on the postmating behavior of the female. We have examined the sequence, structure, and expression of a gene, mst 316, expressed exclusively in the accessory glands of male Drosophila melanogaster. The mst 316 RNA encodes a small, basic protein of 52 amino acids that exhibits features common to precursors of secreted peptides, including a hydrophobic N terminus. The tissue-specific expression of the mst 316 gene was studied using an mst 316--lacZ hybrid gene inserted into Drosophila by germ line transformation. The mst 316-lacZ fusion protein is expressed exclusively in the "main" cells of the accessory gland. It is first detected upon eclosion and exhibits a burst of synthesis in the first 3 days of adult life. The synthesis of the fusion protein is stimulated by mating, so that beta-galactosidase activity levels are two- to sixfold higher in males allowed to copulate with females compared to virgin male controls of the same age. The mating-stimulated synthesis of the mst 316-lacZ fusion protein, and by inference of the native gene product, appears to be due at least in part to increased transcript levels. PMID- 2109713 TI - Effects of ganglioside (Cronassial) treatment on MHC Ia antigen expression and allograft survival of pancreatic islets in diabetic rats. AB - Streptozotocin-diabetic BdII rats were treated daily with 20 mg/kg body weight gangliosides for ten days beginning two days before transplantation. This treatment did not prolong allograft survival of untreated Lewis islets. Culture treatment of isolated Lewis islets with gangliosides (100 micrograms/ml in RPMI 1640) for one day resulted in a significant reduction of MHC Ia antigen positive cells but not of class I antigens within the islets. Transplantation of the ganglioside pretreated islets into non-immunosuppressed BdII recipients prolonged allograft survival to 12 days only in one of five animals. PMID- 2109714 TI - Transplantation analysis of B cell destruction in (NOD x CBA)F1 mouse bone marrow chimeras. AB - F1 hybrids produced by outcross of non-obese diabetic (NOD) mice with diabetes resistant strains are also diabetes resistant. This resistance is abrogated if F1 hybrids are lethally irradiated and then haematopoietically reconstituted with NOD bone marrow. This model was employed to determine whether T lymphocyte recognition and elimination of pancreatic B cells in NOD mice is restricted by the MHC haplotype of the target B cell. Diabetes resistant (NOD/Lt x CBA/J)F1 hybrids were lethally irradiated and reconstituted with NOD/Lt bone marrow. Following haematopoietic reconstitution, donor matched NOD/Lt or CBA/J pancreatic islet and anterior pituitary grafts were grafted under a renal capsule to determine whether effector cells derived from NOD/Lt marrow progenitors would reject islet grafts in a MHC restricted fashion. The H-2k haplotype expressed by CBA/J mice differs from all known loci of the unique H-2 haplotype of NOD; therefore, if NOD/Lt T lymphocytes eliminate pancreatic B cells in a MHC restricted fashion. NOD islet grafts would be eliminated in these chimeras while CBA islet grafts would be retained. Overt diabetes developed in 80% of the female and 40% of the male F1 hybrids following reconstitution with NOD/Lt marrow, while no hybrids reconstituted with CBA/J marrow became diabetic through a year of age. The retention of CBA/J skin and pituitary grafts in NOD/Lt marrow reconstituted F1 hybrids confirmed that the F1 thymic environment imparted tolerance to CBA/J alloantigens. Nonetheless, responses to a T cell dependent model antigen were restricted to the unique MHC haplotype of NOD. This was associated in the hyperglycaemic chimeras with rejection (8-21 days post-implantation) of both CBA/J and NOD/Lt islet grafts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109715 TI - [Cardiac arrhythmia suppression trial (CAST)]. PMID- 2109717 TI - [Juxtapapillary diverticula and biliary lithiasis: a causal relation?]. PMID- 2109716 TI - [Elemental feeding into the distal segment of a temporary small bowel]. AB - Patients who have an interruption of the small bowel with a high enterostomy usually need parenteral supply or reinfusion of chyme to maintain nutritional and electrolytic balances before restoring intestinal continuity. Ten patients (aged 28-76 years) with a terminal jejunostomy located within the first meter of jejunum were treated by infusion of an elemental diet into the distal small bowel (IEDDSB). In addition, five of these patients had an extensive small bowel resection. IEDDSB was started 32 days after operation and lasted 4 to 8 weeks. Mean daily caloric infusion was 1,732 +/- 666 kcal diluted in 2,860 +/- 808 ml; mean associated oral intake was 1,187 +/- 480 kcal/24 hr, and jejunal fecal losses averaged 3 kg per day. IEDDSB was well tolerated in 4 patients; 5 experienced transient abdominal pain or diarrhea; 1 developed severe and protracted diarrhea. Biological cholestasis was seen before IEDDSB and persisted in most patients; 1 patient developed biliary sludge. Through IEDDSB, nutritional status improved or remained satisfactory in 9 patients, and worsened in 1 patient with sepsis and a short lower intestine. Mean body weight, triceps skin fold, muscle circumference, serum albumin, serum transferrin did not change significantly. Digestive nitrogen balance performed in 6 patients showed a net absorption between 5 and 15 g/24 hr. Fluid and electrolyte balance was maintained in 9 patients and 1 received iterative intravenous saline. Digestive sodium balance showed a net absorption rate greater than 60 mmol/24 hr. in all patients, except the one who required intravenous supply. Postoperative recovery was uneventful in all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109718 TI - Genetic transformation of intact cells of Bacillus subtilis by electroporation. AB - Plasmid DNAs were introduced by electroporation into Bacillus subtilis PB1424 as an alternative to competent-cell or protoplast transformation. The maximum electroporation efficiency was 10(4) transformants/microgram DNA. Parameters including growth phase of cells, ionic strength of the suspending medium, concentration and size of plasmid DNAs, amplitude and duration of the pulse, were evaluated in order to determine conditions that improved transformation efficiency. PMID- 2109719 TI - The effect of oligolysines Lys-3, Lys-4, and Lys-5 on the outer membrane permeability of Pseudomonas aeruginosa. AB - A lysine polymer with five residues (Lys-5) was found to remarkably increase the outer membrane (OM) permeability of Pseudomonas aeruginosa to the tested hydrophobic probes (nitrocefin, N-phenyl naphthylamine, rifampin). Lys-3 and Lys 4 were inactive. The OM of Escherichia coli and Salmonella typhimurium was not permeabilized by Lys-5. Furthermore, even the action of Lys-5 on the Pseudomonas OM was abolished when the assays were performed in the presence of 150 mM NaCl instead of the low-ionic strength buffer earlier used by investigators studying the effect of polycations on the Pseudomonas OM. PMID- 2109720 TI - Use of lectins for a comparative study of cell wall composition of different anaerobic rumen fungal strains. AB - The technique based on fluorescein-linked lectins used to determine the cell wall structure of anaerobic rumen fungi belonging to genera: Neocallimastix, Piromonas and Sphaeromonas, appears to be an interesting tool for distinguishing between strains. Furthermore this technique shows differences of cell wall composition between different parts of the thallus (spores, sporangia, rhizoids). PMID- 2109721 TI - Purification and properties of a beta-glucosidase from Penicillium oxalicum autolysates. AB - A beta-glucosidase from the medium of an autolyzed culture of Penicillium oxalicum has been purified by tannic acid precipitation, sephacryl S-200, DEAE Biogel, CM-Biogel and Mono Q successively. The purification process produced a homogeneous band in the SDS-PAGE that correspond to a Mr of 133,500. The enzyme had a pl of 4, and the active optima were found at pH 5.5 and 55 degrees C. The enzyme hydrolyzed different substrates showing maximum affinity against p nitrophenyl-beta-D-glucoside with a Km value of 0.37 mM. The beta-glucosidase was inhibited by Glucono-D-lactone but not by glucose in the concentration range of 1 to 10 mM. The enzyme was adsorbed by Concanavalin-A-Sepharose. PMID- 2109722 TI - Comparison of promoter activities in Escherichia coli and Pseudomonas aeruginosa: use of a new broad-host-range promoter-probe plasmid. AB - The broad-host-range plasmid, pRW2, is a derivative of pRK 2501 carrying the Escherichia coli lac operon without a promoter, downstream of a polylinker sequence. We have cloned a number of DNA fragments carrying promoters into this plasmid and measured promoter activity in both E. coli and Pseudomonas aeruginosa. Promoters carrying consensus -10 and -35 sequences were active in both backgrounds and the dependence of activity on the nucleotide sequence of the 35 region was the same in both cases. We also measured the activity of two promoters at which transcription in E. coli was totally dependent on the E. coli activators CRP and FNR: both promoters were found to be active in P. aeruginosa. PMID- 2109723 TI - Plasmid transformation in Bacillus subtilis NB22, an antifungal-antibiotic iturin producer. AB - A transformation system with plasmids was developed for Bacillus subtilis NB22, an antibiotic iturin producing strain. Treatment of B. subtilis NB22 with 4 M KCl was effective for the induction of competence, followed by uptake of plasmid DNA in the presence of polyethylene glycol. The efficiency of transformation of this bacterium with pC194 and pUB110 was 4.1 X 10(3) and 1.5 X 10(3) transformants per micrograms DNA, respectively and the transformation frequency was 3.3 X 10(-3) and 7.2 X 10(-4), transformants per viable cell, respectively. This method was much faster and three orders of magnitude more efficient in transformation efficiency than protoplast transformation methods. PMID- 2109724 TI - Recognition of novel glycolipid antigens from smooth variants of Mycobacterium tuberculosis. AB - A major polar and three minor slightly less polar glycolipids were identified in extracts of two smooth (Canetti) strains of Mycobacterium tuberculosis. Immunostaining on thin-layer chromatograms and enzyme-linked immunosorbent assay (ELISA) of purified lipids demonstrated that the major and the two most polar of the minor glycolipids are potent antigens, reacting with homologous antisera and also with that raised against the type strain (H37Rv). PMID- 2109725 TI - [Economic evaluation of health-related effects of the improvement of working conditions]. AB - The importance of financial resources input into health improving goes without saying, and economic analysis can only contribute to the search and allocation of funds. The specific economic loss (SEL) seems to be a most informative index of the damage caused to economy by occupational diseases. This index includes the total sum of economic damage of the society through all the life of the worker after an occupational disease was diagnosed. The limits of SEL vary from 6.8 to 30 thousand roubles. A further elaboration of technical and legislative bases is needed to define the economic responsibility of enterprises for violating hygienic norms and regulations. PMID- 2109726 TI - [Pharmacological profile of mofezolac, a new non-steroidal analgesic anti inflammatory drug]. AB - Pharmacological activities of mofezolac were investigated in experimental animal models and compared with those of indomethacin, ibuprofen, mefenamic acid, aspirin and aminopyrine. Mofezolac showed a potent suppression of various writhing models in mice or rats; and its potency was slightly lower than that of indomethacin, but was higher than those of the other reference drugs. Thus, mofezolac was especially active against chemically induced writhing and also in the phenylquinone induced intraperitoneal dye leakage reaction in mice. Mofezolac also has a potent inhibitory activity on the algesic responses induced by the mechanical stimulus of the inflammed tissue. Mofezolac exhibited a therapeutic effect comparable to indomethacin in the urate synovitis in dogs. Considering the anti-inflammatory and antipyretic actions, mofezolac was obviously less effective than indomethacin, and its potency was similar to that of ibuprofen. The ulcerogenic effect of mofezolac on the gastric mucosa was far weaker than that of indomethacin. In in vitro studies, the prostaglandin biosynthesis and platelet aggregation were inhibited to the same extent by both mofezolac and indomethacin. Accordingly, it may be considered that the actions of mofezolac are due to the inhibition of cyclooxygenase. Our result suggest that mofezolac can be a useful drug that shows a rapid pain-relieving activity in acute inflammations. PMID- 2109727 TI - [Surgical treatment of drug resistant epilepsy]. AB - Even today, epilepsy is resistant to conservative treatment in a certain number of patients. In many of these cases surgical treatment is a meaningful alternative. The most important procedure is the resection of the epileptogenic focus. Thus, surgical treatment is only possible if the preoperative evaluation of the patient reveals a focus in a resectable area of the brain. In this article the modern electrophysiological, nuclear medical and neuroradiological diagnostic procedures, together with the various surgical procedures of surgery for epilepsy are presented. PMID- 2109728 TI - [Analysis of factors concerning geriatric medical expenditures in Hokkaido]. PMID- 2109729 TI - A randomized trial of terlipressin plus nitroglycerin vs. balloon tamponade in the control of acute variceal hemorrhage. AB - A randomized trial was undertaken to determine the efficacy of nitroglycerin in addition to terlipressin infusion to improve the control of acute variceal hemorrhage compared with balloon tamponade. Forty-seven bleeding episodes in 34 cirrhotic patients were included, with terlipressin plus sublingual nitroglycerin in 23 episodes (group I) and balloon tamponade in 24 episodes (group II). At the end of the 12-hr period, hemorrhage had been equally controlled in both groups (18 of 23; 78% in group I and 19 of 24; 79% in group II). When attempted, balloon tamponade appeared more efficient in the failures of group I (4 of 4) than did terlipressin plus nitroglycerin in the failures of group II (0 of 3), although this difference was not significant. Major complications were rare (one in each group) and never required cessation of therapy. Thus terlipressin and nitroglycerin were as effective as balloon tamponade in controlling variceal hemorrhage and were associated with few minor complications. PMID- 2109730 TI - Ek alpha transgene in B10 mice suppresses the development of myasthenia gravis. AB - Mice bearing the H-2b haplotype are susceptible to the development of experimental autoimmune myasthenia gravis (EAMG), induced by acetylcholine receptor (AChR) autoimmunity. One of the genes influencing EAMG susceptibility has been mapped to the Ab locus of the major histocompatibility complex, and the A beta chain has been implicated in the pathogenesis. Mice of the H-2b haplotype, including C57BL/10 (B10), have a genomic deletion of the E alpha gene and therefore fail to express the E molecule on their cell surface. To test the hypothesis that failure to express the cell surface E molecule in B10 mice contributes to EAMG pathogenesis, Ek alpha transgenic B10 mice expressing the E molecule were examined. Expression of the E molecule in Ek alpha transgenic B10 mice partially prevented the development of EAMG. PMID- 2109731 TI - Production of thromboxanes by transformed lymphocytes--effect on heart contractility. AB - We studied the effect of transformed lymphocytes from patients with chronic lymphocytic leukaemia (CLL) and the Raji cell (Raji) on the response of rat isolated atria to sodium arachidonate (AA). In contrast to normal lymphocytes, CLL cells and Raji cells decrease the contractile tension of rat isolated atria. Addition of exogenous AA (1.98 X 10(-6) M) to Raji, further reduced the isometric developed tension. Time of culture of Raji was important, as the negative inotropic effect was greater at 72 h than at 24 h of culture. Living cells were required and cell-free supernatants were inactive. Preincubation of CLL cells or Raji with cyclooxygenase inhibitors (acetyl salycilic acid, indomethacin) or inhibitors of thromboxane (TX) synthesis (imidazole, L-8027) abolished the negative inotropic response suggesting the contribution of TXs. L-8027 also reduced the growth rate of Raji cells, indicating that TXs may play a role in the regulation of cell division. The production of TXs by CLL and Raji cells from both endogenous and exogenous sources provided additional support to this hypothesis and suggested that activation of this metabolic pathway may be related to cell transformation. PMID- 2109732 TI - 1-naphthyl N-methyl carbamate effect on intra- and extracellular concentrations of arachidonic acid metabolites, and on the chemiluminescence generation by mouse peritoneal macrophages. AB - 1-Naphthyl N-methyl carbamate (carbaryl), potent carbamate insecticide with anticholinesterase activity, was tested for its ability to affect mouse peritoneal macrophages in particular arachidonic acid (AA) metabolism and oxidative burst. Carbaryl inhibited in a dose-related manner the reactive oxygen intermediate dependent chemiluminescence (CL) induced by opsonized zymosan (OZ), 12-O-tetradecanoyl phorbol-13-acetate (TPA) and calcium ionophore (A23187); this carbamate did not affect CL-mediated by AA. The intracellular and extracellular concentrations of prostaglandins (PGs) and 5-hydroxyeicosatetraenoic (5-HETE) generated in macrophages stimulated with OZ has been investigated for various periods. Carbaryl effect displayed two successive phases on AA metabolism stimulation. In a first phase (up to 2-15 min), carbaryl did not alter the rapid AA metabolite synthesis (total amount of intra- and extracellular metabolites) but it increased intracellular concentration of PGE2, PGA2, PGF2 alpha and decreased 5-HETE intracellular concentration. In a second phase (after 2-15 min), carbaryl inhibited AA metabolite synthesis. The release of cyclooxygenase (CO) and lipoxygenase (LO) metabolites decreased, in particular PGF2 alpha and PGD2 which in addition seemed to be submit to a cellular retention; the inhibition of other metabolite release appeared essentially related to the inhibition of their synthesis since the intracellular amount did not augment. The inhibition by carbaryl of the NADPH-oxidase dependent CL induced by OZ may be related to the alteration of the intra- and extracellular concentrations of AA metabolites. PMID- 2109733 TI - Effect of specific chemotherapy on the immune response and resistance to reinfection in experimental Schistosomiasis mansoni. AB - Mice infected for 45 days with 120 Schistosoma mansoni cercariae and treated with praziquantel in a dose of 500 mg/kg for two consecutive days had a significant lower resistance to reinfection when challenged two weeks after treatment (45% compared to 88% in infected challenged untreated mice). In praziquantel-treated mice, the reduction in the per cent resistance was accompanied by a diminution in the size of hepatic granulomata and its in vivo correlate the delayed foot pad swelling. Moreover, the granuloma proportionate T-cell subset enumeration revealed a significant reduction in the number of T-helper cells. The humoral immune response as measured by the immediate foot pad swelling was not affected by praziquantel. Results reveal besides the diminution of the state in resistance to reinfection after praziquantel, possible involvement of egg-related pathology as a T-cell mediated reaction and as a mechanical obstacle in maintenance of this resistance. PMID- 2109734 TI - Inhibition of prostaglandin and leukotriene generation by the plant alkaloids tetrandrine and berbamine. AB - We compared the effects of two bisbenzylisoquinoline compounds on leukotriene and prostaglandin generation by human monocytes and neutrophils. The results show that tetrandrine had a much greater effect than berbamine on leukotriene generation. However, both compounds were equally potent in suppression of prostaglandin generation. This inhibitory effect on prostaglandin generation can be overcome by exogenous arachidonic acid (AA), suggesting that the site of inhibition is not on the cyclooxygenase enzyme complex, but more proximally on the phospholipase-mediated release of AA from the cell membrane, similar to the action of corticosteroids. These results, together with previous findings of inhibitory effects on other inflammatory mediators such as histamine, platelet activating-factor (PAF) and interleukin 1 (IL-1) indicate that these plant alkaloids may be useful lead compounds for the development of a new class of anti inflammatory drugs. PMID- 2109735 TI - A second species of Bacillus causing primary cutaneous disease. PMID- 2109736 TI - Cutaneous thrombosis, cerebrovascular thrombosis, and lupus anticoagulant--the Sneddon syndrome. Report of 10 cases. AB - Ten patients with circulating lupus anticoagulant who presented with cutaneous vascular disease and cerebrovascular disease are presented. Cutaneous manifestations were gangrene, thrombophlebitis, ulcers, and livedo reticularis. All 10 patients had cerebral infarction. The relationship between the cerebral and cutaneous vascular changes and the presence of lupus anticoagulant is supported by a common noninflammatory vascular thrombosis histologically in these patients and by the presence of similar pathologic and clinical findings in patients with the lupus anticoagulant syndrome. PMID- 2109737 TI - Darwin's illness. PMID- 2109738 TI - The fairness of the PPS reimbursement methodology. AB - In FY 1984 the Medicare program implemented a new method of reimbursing hospitals for inpatient services, the Prospective Payment System (PPS). Under this system, hospitals are paid a predetermined amount per Medicare discharge, which varies according to certain patient and hospital characteristics. This article investigates the presence of systematic biases and other potential imperfections in the PPS reimbursement methodology as revealed by its effects on Medicare operating ratios. The study covers the first three years of the PPS (approximately 1984-1986) and is based on hospital data from the Medicare cost reports and other related sources. Regression techniques were applied to these data to determine how Medicare operating ratios were affected by specific aspects of the reimbursement methodology. Several possible imbalances were detected. The potential undercompensation relating to these can be harmful to certain classes of hospitals and to the Medicare populations that they serve. PMID- 2109739 TI - Quality of long-term care in nursing homes and swing-bed hospitals. AB - By 1989, more than 1,100 hospitals in rural communities throughout the United States were using hospital beds as swing beds to provide both long-term and acute care. In this study, the quality of long-term care in swing-bed hospitals was compared with the quality of nursing home care, using patient outcomes along with both process and structural measures of quality. Several methodological and conceptual points on measuring and analyzing the quality of long-term care are discussed in this article. Data were analyzed on approximately 2,000 patients in four different primary data samples, three of which were longitudinal involving multiple follow-up points. An analysis of changes in patient status over time, hospitalization rates, rates of discharge to independent living, services provided, and certain structural indicators showed that (1) relative to nursing home care, swing-bed care is more effective in enhancing functional outcomes and discharge to independent living and in reducing hospitalization for long-term care patients, and (2) nursing home care appears more desirable than swing-bed care for long-stay, chronic care patients with no rehabilitation potential. Swing bed hospitals have gravitated largely to admitting postacute long-term care patients. They do not typically compete directly with community nursing homes for chronic care patients. The greater effectiveness of swing-bed care for patients with near-acute long-term care needs suggests that this approach should be considered in urban communities and that we should scrutinize our current tendency to place in traditional nursing homes many patients who have at least some rehabilitation potential. PMID- 2109740 TI - A comparison of in-house and regionalized computerized tomography scanning: clinical impact and cost. AB - Over a two-year interval, computerized tomography (CT) scans at an urban, 400-bed Department of Veterans Affairs medical center (VAMC) were obtained in three ways. First, an in-house low-efficiency machine was used. Then, scans were done at another area hospital, in effect duplicating some aspects of regionalizing services. Finally, a high-efficiency in-house machine was used. Clinical outcomes and costs of diagnosing 181 bronchogenic cancer patients were compared across the three time periods to identify any differences associated with regionalization of CT services. Patient groups were homogeneous with respect to sociodemographic characteristics, clinical presentation, and severity of disease. The first part of the analysis investigated whether the site of CT scanning affected clinical outcomes. Diagnostic procedures, surgical results, mortality, and length of stay were compared using one-way analysis of variance. Significant differences were found only for conventional tomography and CT utilization rates. While conventional tomography declined across the periods, CT utilization increased, exceeding national trends. The second part of the analysis examined the costs of CT scanning. During the regionalized period, the hospital paid a fixed fee of $519 per scan. Estimated costs of in-house scans were $285 in the low-efficiency and $141 in the high-efficiency periods. Charge-based payments made to the external facility and differences in the volumes of patients scanned internally account for the cost differences. The analysis showed that while regionalized CT scanning did not compromise the quality of care for these VA patients, it was more costly. Results suggest that VA hospital administrators should carefully consider ownership and payment arrangements when comparing regionalized and in house provision of services. PMID- 2109741 TI - Risk factors for early readmission among veterans. AB - This study was undertaken to identify demographic, clinical, and social risk factors for early readmission in the veteran population. Readmissions within 30 days of discharge were considered "early." A randomly selected 50 percent sample of 6,317 veterans discharged consecutively from one Department of Veterans Affairs medical center (VAMC) was used to build a logistic regression model for early readmission. Of these patients, 22 percent had early readmissions. The adjusted odds ratios (OR) of greater magnitude for early readmission (p less than .05) were associated with discharge from a geriatrics/intermediate care bed (OR = 2.75 relative to medical ward), discharge diagnosis of a chronic disease (OR = 2.03-2.67 relative to acute or self-limiting disorders), and two or more surgical procedures performed during the index admission (OR = 1.87 relative to no surgery). Increasing distance from the VA hospital and increasing age also added readmission risk (OR = 1.18 and 1.10, respectively). Length of stay and the social risk factors of marital status and place of disposition were not sufficiently predictive to enter the model. The model was validated successfully on the second 50 percent sample of patients. We conclude that clinical and demographic factors are more predictive of early readmission than are social factors. Early readmission models could be used to improve VA discharge planning and to focus quality assurance and utilization review efforts on providers whose early readmission rates exceed those predicted by the models. PMID- 2109742 TI - Assessing the effects of the Medicare Prospective Payment System on the demand for VA inpatient services: an examination of transfers and discharges of problem patients. AB - An examination of patient data from three medical districts that vary in urban/rural composition and in their proportion of proprietary hospitals was undertaken to determine if high-cost patients whose illnesses place them in "problem" DRGs (diagnosis-related groups identified as "problems" through interviews with private hospital administrators and from information published by the Wisconsin Hospital Association) are being shifted from non-Department of Veterans Affairs (non-VA) hospitals to VA hospitals. Two outcome measures were employed to detect shifting: patient transfers between non-VA and VA hospitals and discharges of veterans in a sample of DRGs identified as unprofitable by private hospitals. A comparison of patient transfers for fiscal year 1982 and fiscal year 1984 (pre- and post-DRG implementation) revealed substantial increases in the number of transfers, but there appeared to be no concentration of transfers in particular DRGs. An examination of discharges for FY 1982 and FY 1984 within 21 problem DRGs showed average increases ranging from 27 percent to 41 percent among patients aged 65 years or older. A comparison of discharges within a sample of 21 randomly selected DRGs showed either no increase or small decreases in discharges from FY 1982 to FY 1984. The possibility is discussed that some of the cost reductions (or slowing of the rise in costs) attributed to the prospective payment system are merely phantom savings. Hospitals may simply be shifting costs from Medicare to the VA system. PMID- 2109743 TI - Relationship between lectin binding properties and the expression of blood group ABH antigens in vascular endothelia and red blood cells from 18 primate species. AB - The reactivity was examined of horseradish peroxidase labelled Ulex europaeus agglutinin-I (UEA-I) and Griffonia simplicifolia agglutinin I-B4 (GSAI-B4) with red blood cells and vascular endothelium in formalin-fixed, paraffin embedded tissues from 18 primate species. The expression of blood group ABH antigens in these cells as well as secretions from other tissues was also examined by the indirect immunoperoxidase method using monoclonal anti-ABH antibodies as primary antibodies. In Prosimians and New World monkeys which lack ABH antigens on both red blood cells and endothelial cells, but produce these antigens in other tissue secretions, GSAI-B4 always reacted with both red blood cells and endothelial cells. In Old World monkeys, which express blood group antigens on endothelial cells but not on red blood cells, neither GSAI-B4 nor UEA-I reactivity were observed, except the endothelial cells from blood group B or O individuals occasionally reacted with GSAI-B4 or UEA-I, respectively. Although UEA-I reactivity was not observed in the endothelial cells of gibbon, it reacted with these cells from chimpanzees. In these two anthropoid apes, both endothelial cells and red blood cells expressed ABH antigens as in humans. These results suggest the close evolutionary relationship between the expression of blood group ABH antigens and lectin binding properties of red blood cells and endothelial cells in primate species. PMID- 2109744 TI - Carboxylic ester hydrolases in mitochondria from rat skeletal muscle. AB - A mitochondrial pellet, prepared from rat skeletal muscle, contained a number of carboxylic ester hydrolase isoenzymes. The esterases which split alpha-naphthyl acetate were organophosphate sensitive, whereas two out of three indoxyl acetate hydrolysing enzymes were resistant to both organophosphate and organomercury. The activity of the indoxyl acetate esterases was enhanced by the non-ionic detergents Tween-40 and Lubrol. After freezing, thawing and high speed centrifugation most of the alpha-naphthyl acetate splitting enzymes were found in the supernatant, indicating that the enzymes are loosely bound to mitochondrial membranes. PMID- 2109745 TI - Plasminogen activator inhibitor-type 1 in Lewis lung carcinoma. AB - Plasminogen activator inhibitor-type 1 (PAI-1) was identified in extracts of Lewis lung carcinoma, and its immunohistochemical localization was studied together with that of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators. All primary tumors (n = 11) contained heterogeneously distributed immunoreactivity against each of the three components. Most often, areas that contained u-PA immunoreactivity also contained PAI-1 immunoreactivity. However, several areas showed a strong u-PA immunoreactivity, but no or low PAI-1 immunoreactivity. The latter staining pattern was only found in peripheral areas, and usually in areas with histological signs of tissue destruction. Lung metastases always contained u-PA immunoreactivity, while PAI-1 immunoreactivity was found in most, but not all, metastases. t-PA immunoreactivity was found in a few scattered tumor cells, in primary carcinomas as well as metastases. Controls that included absorption with highly purified antigen preparations and immunoblotting, indicated that all the immunoreactivity represented genuine PAI 1, u-PA and t-PA, respectively. The results are consistent with an assumption that the plasminogen activation system, and particularly u-PA and PAI-1, plays a role in regulation of breakdown of extracellular matrix proteins during invasive growth in this carcinoma. PMID- 2109746 TI - Condemnation of beef because of Sarcocystis hirsuta infection. AB - Carcasses from 18 Holstein cows from Nevada, California, and Oregon were condemned because of grossly visible sarcocysts of Sarcocystis hirsuta. Sarcocysts were white to dull white, 2 to 7 mm long, and approximately 1 mm wide. Sarcocysts were most numerous in muscles of diaphragm, flank, and limbs and were able to infect laboratory-raised cats. PMID- 2109747 TI - Stereocilia bundle stiffness: effects of neomycin sulphate, A23187 and concanavalin A. AB - The effects that the aminoglycoside antibiotic neomycin sulphate, the ionophore A23187 and the lectin Concanavalin A (Con A) have on the steady state stiffness of the hair-cell stereocilia bundle have been studied using organotypic cultures of the early postnatal mouse cochlea. In normal saline, stereocilia bundle stiffness is increased 1.5-2.0 fold by neomycin sulphate, 1.3-1.7 fold by the ionophore A23187 and 3.0-5.0 fold by Con A. In low-calcium saline neither neomycin sulphate nor A23187 cause increases in stiffness, and the stiffness increases elicited by these two agents in normal saline are reversed on washout with low-calcium saline. In normal saline neomycin sulphate has two independent effects on hair cells; one effect is a reversible inhibition of transduction and the other effect is to cause an irreversible increase in bundle stiffness. Neither Con A nor the ionophore A23187 block transduction. No obvious changes in stereocilia bundle morphology are associated with the increases in stiffness caused by neomycin sulphate, A23187 and Con A. Succinylated Con A binds to stereocilia bundles but does not cause an increase in stiffness, suggesting that the stiffness increase caused by native Con A results from receptor cross linking. The effects of Con A and neomycin are non-additive, saturating concentrations of neomycin sulphate block the effects of low doses of Con A, and pretreatment of cells with succinylated Con A prevents subsequent neomycin sulphate treatment from causing an increase in stiffness suggesting that neomycin sulphate and Con A are acting via a similar mechanism at the cell surface. Ionophore treatment prevents the subsequent application of neomycin sulphate from causing a further increase in stiffness, but when cells are treated with neomycin sulphate followed by ionophore the effects of the two drugs are additive indicating that they are operating via different mechanisms. The possible nature of these mechanisms and their role in the control of steady state stereocilia bundle stiffness are discussed. PMID- 2109748 TI - Decreases of the susceptibility to low molecular weight beta-lactam antibiotics in imipenem-resistant Pseudomonas aeruginosa mutants: role of outer membrane protein D2 in their diffusion. AB - Decreased susceptibilities to two low Mr beta-lactam antibiotics, CS-533 (a carbapenem; Mr, 339) and CGP31608 (a penem; Mr, 262), were found in imipenem resistant mutants of Pseudomonas aeruginosa PAO. The diffusion rates of several beta-lactam antibiotics including imipenem, CS-533 and CGP31608 across the proteoliposome membrane reconstituted from the outer membrane of the wild type strain or its imipenem-resistant mutants were determined by the liposome swelling technique. Diffusion rates of imipenem, CS-533 and CGP31608 in the proteoliposomes from outer membranes of the imipenem-resistant strain were found to be 27, 20 and 47%, respectively, of the diffusion rates in proteoliposomes reconstituted from outer membranes of the sensitive parent strain. The SDS polyacrylamide gel electrophoretogram of outer membrane proteins of the imipenem resistant strains indicated deletion of protein D2. These results suggested that decreased susceptibilities to imipenem, CS-533 and CGP31608 were due to decreased outer membrane permeability, and that D2 is a protein fraction constituting pores for diffusion of these antibiotics through the P. aeruginosa outer membrane. PMID- 2109750 TI - Use of the acyl azide method for cross-linking collagen-rich tissues such as pericardium. AB - Collagen biomaterials should be cross-linked in order to prevent biodegradation when they are used as implants. We have compared the cross-linking efficiencies of glutaraldehyde and acyl azide in pericardium. Glutaraldehyde is used currently, but it elicits a cytotoxic effect which reduces the biocompatibility of cross-linked tissue. We have attempted to overcome this problem by developing a cross-linking method that obviates incorporation of foreign agents. Our process involves transformation of free carboxyl groups on collagen into acyl azide groups, which react with free amino groups on adjacent side chains. We have shown that the greatest increase in the thermal stability of collagen, as measured by differential scanning calorimetry, is achieved when tissue swelling is inhibited by the addition of sodium chloride (1 M) during acyl azide formation. Under these conditions, the denaturation temperature (Td) of pericardial collagen treated with acyl azide is raised to 83.4 degrees C and that of tissue treated with glutaraldehyde to 85.1 degrees C. Moreover, acyl-azide-treated tissues have the same resistance as glutaraldehyde-treated tissues to chemical solubilization by cyanogen bromide and to enzymatic digestion by collagenase. PMID- 2109751 TI - Dimethylthiourea reduces ischemic brain edema without affecting cerebral blood flow. AB - Oxygen free radicals have been implicated as mediators of tissue damage in ischemic brain. We previously demonstrated that the hydroxyl radical scavenger 1,3-dimethyl-2-thiourea (DMTU) reduces infarct size after middle cerebral artery occlusion (MCAO) in rats. The present study was undertaken to determine whether this protection results from a preservation of the CBF. Adult male Sprague-Dawley rats were treated with DMTU (750 mg/kg i.p.) or saline vehicle 1 h before right MCAO. One-half 4, or 24 h after MCAO, animals were killed and samples were taken from the central, intermediate, and outer zones of the MCA distribution of each cortical mantle. Separate groups of animals were used to analyze these samples for water content (wet and dry weight), CBF [( 14C]butanol), or blood-brain barrier permeability [( 3H]alpha-aminoisobutyric acid). CBF was reduced in a graded fashion in the ischemic cortex: 0.169 +/- 0.020, 0.261 +/- 0.017, and 0.435 +/- 0.023 ml/g/min (mean +/- SEM, n = 8) after 4 h in the central, intermediate, and outer zones, respectively. Brain edema was present in a similar pattern, while blood-brain barrier permeability remained normal. Treatment with DMTU significantly reduced brain edema in the central and intermediate zones at both 4 and 24 h. However, CBF in the DMTU-treated animals was identical to that of the vehicle-treated animals. These results suggest that hydroxyl radicals play a role in the development of ischemic brain edema, but the mechanism does not appear to involve a direct effect on CBF. PMID- 2109752 TI - Spigelian hernia: some amendments. PMID- 2109749 TI - Membrane fusion of enveloped viruses: especially a matter of proteins. AB - To infect mammalian cells, enveloped viruses have to deposit their nucleocapsids into the cytoplasm of a host cell. Membrane fusion represents a key element in this entry mechanism. The fusion activity resides in specific, virally encoded membrane glycoproteins. Some molecular properties of these fusion proteins will be briefly described. These properties will then be correlated to the ability of a virus to fuse with target membranes, and to induce cell-cell fusion. Some molecular and physical parameters affecting virus fusion--at the level of either viral or target membrane or both--and the significance of modelling virus fusion by using synthetic peptides resembling viral fusion peptides, will also be discussed. PMID- 2109753 TI - Substance abuse by adolescents. PMID- 2109754 TI - The prevention of P. carinii pneumonia. PMID- 2109755 TI - Depression with and without dementia. PMID- 2109756 TI - Coronary angioplasty in myocardial infarction. AB - Criteria for emergency and elective use of the technique are evolving. Clinical trials have established the role of elective angioplasty after intravenous thrombolysis for patients with signs of spontaneous or inducible ischemia. On the other hand, prophylactic angioplasty in the first two days after thrombolysis appears to be undesirable in most cases. PMID- 2109757 TI - Decisions in P. carinii pneumonia. PMID- 2109758 TI - Abdominal pain and a pelvic mass. PMID- 2109759 TI - Chronic constipation: causes and management. PMID- 2109760 TI - Simultaneous determination of pantothenic acid and hopantenic acid in biological samples and natural products by gas chromatography-mass fragmentography. AB - A method for the simultaneous determination of pantothenic acid and hopantenic acid in plasma samples was developed using gas chromatography-mass spectrometry with multiple ion detection. Plasma samples were directly purified without deproteinization on an ion-exchange resin, and the eluate was extracted with ethyl acetate under acidic conditions. The organic layer was evaporated to dryness under a stream of nitrogen, and the residue was dissolved in an internal standard solution. Pantothenic and hopantenic acids were converted into their trimethylsilyl derivatives by treating with bis(trimethylsilyl)trifluoroacetamide. Aliquots of this solution were injected into the gas chromatograph-mass spectrometer, which was equipped with a wide-bore fused-silica column (DB-17) and analysed by the multiple ion detection method. The detection limits for pantothenic acid and hopantenic acid in plasma were 1 ng/ml each at a signal-to-noise ratio of 5. This method was applied to a study of the assay of pantothenic acid and hopantenic acid in biological samples and natural products. PMID- 2109761 TI - Purification of phospholipase-C from Bacillus cereus by affinity chromatography on 2-(4-aminophenylsulphonyl)ethyl-cellulose. AB - A new method for the purification of phospholipase-C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) from Bacillus cereus has been developed, based on its affinity to 2-(4-aminophenylsulphonyl)ethyl derivative of beaded cellulose. The enzyme was adsorbed on the affinity sorbent through a site(s) that was clearly distinct from its catalytically active site, because it was still active in the immobilized state. A possible role of enzyme-inhibitor interaction in enzyme binding to the ligand used is discussed. PMID- 2109762 TI - Modulation of bullous pemphigoid antigens by gamma interferon in cultured human keratinocytes. AB - We report the effects of human recombinant gamma interferon (gamma-IFN) on the expression of bullous pemphigoid (BP) antigens by human cultured keratinocytes. Secondary epidermal cell cultures were grown on 3T3 mouse fibroblasts; when confluent, some cultures were maintained in control medium while others were exposed to various concentrations of gamma-IFN (100, 200, 400 U/ml) for 14 days. The expression of BP antigens was analyzed by indirect immunofluorescence on epithelial sheets and immunoblotting of Tris, SDS, beta-mercaptoethanol culture extracts using different BP sera. Our results show that gamma-IFN alters the expression of BP antigens in a way varying according to the skin donor: we observed results ranging from complete loss and decreased expression to unchanged reactivity patterns. Thus, gamma-IFN modifies BP antigen expression; this behavior has been previously shown for other adhesion molecules such as fibronectin and thrombospondin. However, the observed variability of the expression of BP antigens according to the skin donor suggests an unexpected variability in keratinocyte sensitivity to gamma interferon, which remains to be explored both in vitro and in vivo. PMID- 2109763 TI - Acute myocardial dysfunction and recovery: a common occurrence after coronary bypass surgery. AB - To evaluate whether acute myocardial dysfunction was common in the early postoperative period, serial hemodynamic measurements and radionuclide evaluation of ventricular function were performed before and after operation in 24 patients undergoing elective coronary bypass surgery. All patients had uncomplicated surgery, and no patient sustained an intraoperative infarction. In 96% of patients, significant depression in right and left ventricular ejection fraction was seen postoperatively, reaching a nadir at 262 +/- 116 min after coronary bypass. Left ventricular ejection fraction was 58 +/- 12% preoperatively and 37 +/- 10% at trough. Right ventricular function displayed a similar pattern. These findings were also associated with depressed cardiac and left ventricular stroke work index despite maintenance of adequate ventricular filling pressures and mean arterial pressure. The depression in ventricular function was partially reversible within 8 to 10 h after surgery. Left ventricular ejection fraction had increased to 55 +/- 13% at 426 +/- 77 min after coronary bypass and showed complete recovery within 48 h. Left ventricular end-systolic and end-diastolic volume index increased significantly postoperatively, but recovery in left ventricular ejection fraction was mostly due to decreases in end-systolic volume index (50 +/- 22 ml at trough and 32 +/- 16 ml at recovery). Depressed myocardial function was independent of bypass time, number of grafts placed, preoperative medications or core temperatures postoperatively. Postoperative therapy with pressors or inotropic agents delayed but did not prevent the occurrence of postoperative ventricular dysfunction. Despite improvements in operative techniques and methods of myocardial protection, postoperative left ventricular dysfunction continues to be common in patients undergoing cardiopulmonary bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109764 TI - Tocainide: interstitial pneumonitis. PMID- 2109765 TI - Pain in the nursing home. AB - Pain is an understudied problem in geriatric medicine and especially among nursing home residents. The focus of this study was to describe the scope of the problem of pain in a long-term care facility. Ninety-seven subjects from a 311 bed multilevel teaching nursing home were interviewed, and charts were reviewed for pain problems and management strategies. Functional status, depression, and cognitive impairment were also evaluated. Results indicate that 71% of residents had at least one pain complaint (range, 1-4). Of subjects with pain, 34% described constant (continuous) pain and 66% described intermittent pain. Of 43 subjects with intermittent pain, 51% described pain on a daily basis. Major sources of pain included low back pain (40%), arthritis of appendicular joints (24%), previous fracture sites (14%), and neuropathies (11%). Moderately strong correlations were found between pain and infrequent attendance at recreational and social activities (r = .50). However, little correlation was observed between pain and the Yesavage Depression Scale, the Folstein Mini-Mental State Scale, or basic ADLs measured by the Katz Scale. Pain-management strategies consisted of analgesic drugs, physical therapy, and heating pads. Only 15% of patients with pain had received medication within the previous 24 hours. The findings suggest that pain is a major problem in long-term care. Strategies for pain management appear to be limited in scope and application in this setting. Important barriers were identified that influence the reporting and management of pain in this setting. PMID- 2109766 TI - Profile of urinary incontinent elderly in long-term care institutions. AB - This article presents a profile of incontinent elderly in long-term care institutions. One hundred thirty-three frail elderly women were recruited from seven nursing homes in central Pennsylvania for a three-year clinical trial to test the effectiveness of a behavioral therapy on urinary incontinence. All of the patients had more than one medical diagnosis. Eighty percent had cardiorespiratory conditions; the most prevalent diagnoses were cardiovascular diseases. Eighty percent had one or more neurological diseases, including "organic brain syndrome" (47%) and senile dementia (30%); 44% had arthritis/rheumatism. Half of the patients showed severe cognitive impairment; only 12% showed no cognitive impairment. Sixty-three percent were totally dependent; 68% used wheelchairs, 61% were chairbound; 50% had impairments in vision, one-third in hearing, and 14% in speech. Normal bladder capacity, absence of detrusor instability, and satisfactory bladder emptying, as evidenced by low residual urines, was found in 41% of the patients, suggesting that incontinence in this elderly group may not be a primary bladder problem, but rather that mental and physical disabilities may be a more important underlying cause of incontinence in these patients. An important finding in this study is that 34% of the patients had detrusor instability. It is theoretically possible that pharmacologic therapy with anticholinergic agents or imipramine could improve incontinence in this group. Five percent were found to have large residual urine volumes in association with high-capacity bladders suggesting overflow incontinence as the cause of their daily leakage. Pelvic relaxation and stress leakage was far less common in this elderly group of nursing home patients than in young and middle-aged women. PMID- 2109767 TI - Caregiver burden should be evaluated during geriatric assessment. AB - This study examines the relationship between caregiver burden and use of long term care services following geriatric assessment. One hundred nine older subjects underwent comprehensive assessment, which included a questionnaire completed by the primary caregiver to assess the sense of burden in providing care. Logistic regression was used to identify independent predictors of service use at 12 months. Among measures of the older person's cognitive and physical abilities, only activities of daily living predicted increased use of services. When the measure of caregiver burden was added, it also entered as an independent predictor, which significantly improved the prediction of service use (chi 2 = 5.9, P less than .02). In a separate analysis, caregiver burden predicted both the use of home services and nursing-home placement. During longitudinal follow up, the measure of burden decreased over 12 months for the sample, with the greatest reduction in burden occurring for caregivers whose relative was placed in a nursing home. The fact that caregiver burden was the most important factor in determining who would use formal services suggests that burden should be evaluated as part of geriatric assessment. PMID- 2109768 TI - Dissenting opinions regarding telephone communication. PMID- 2109769 TI - Communication between primary physicians and staff of long-term care facilities. PMID- 2109770 TI - Take as directed. PMID- 2109771 TI - Effect of pulsatile luteinizing hormone-releasing hormone administration on pituitary-gonadal function in elderly man. AB - The effect of short-term pulsatile LHRH administration was studied in 8 healthy subjects ranging from 60 to 81 yr to see if the decrease of pituitary gonadal function could be in part due to changes in the discharge of LHRH from the hypothalamus. Gonadotropin and testosterone (T) secretion was evaluated two weeks before and during LHRH (122-160 ng/kg bw every 120 min sc) infusion. In addition, a bolus dosage of LHRH (50 mu iv) was given both at the beginning and at the end of pulsatile LHRH administration in order to test gonadotrophs sensitivity. A significant increase in gonadotropin levels from day 0 to day 4 was found, and was followed by a subsequent decrease from day 7 to day 14. A slight significant increase in T levels was observed during LHRH administration (p less than 0.01). LH pulses were identified in 5 out of 8 subjects on day 0. On day 14, all the exogenous LHRH pulses were followed by significant LH bursts. There was not a significant decrease in the pituitary LH responsiveness to LHRH test from day 0 to day 14. Our study seems to indicate that pituitary - gonadal unit in normal elderly men can be modulated by pulsatile administration of LHRH. A pulse frequency of LHRH which is probably similar to the physiological one, could induce a slight increase in T levels via qualitative changes in LH activity. We can assume that clinical changes in gonadal activity might also be connected to some disturbances in endogenous LHRH pulsar. PMID- 2109772 TI - Thyroid dysfunction in a prospectively followed series of patients with progressive systemic sclerosis. AB - Thirty-nine patients with progressive systemic sclerosis (PSS) in stable clinical conditions were extensively evaluated for the presence of thyroid disease. Two patients had previously undetected hypothyroidism while 7 additional patients had normal serum thyroid hormone levels but an exaggerated TSH response to thyrotropin-releasing hormone (TRH) administration, consistent with subclinical hypothyroidism. Four of the 9 subjects with abnormal TRH responses had positive antithyroid antibodies and of the remaining 5, 4 had been on chlorambucil or prednisone. Basal TSH and TSH response to TRH were significantly higher in PSS patients as a group when compared to a control group and increased with increasing duration of PSS. Serum antithyroid antibodies (antithyroglobulin and/or antimicrosomal antibodies) were positive in 18% and thyroid scans were abnormal in 18% of the patients. The euthyroid sick syndrome was not seen. Our findings indicate an increased frequency of, sometimes previously unsuspected, clinical and subclinical hypothyroidism in stable PSS patients which appears to be autoimmune in nature and becomes more prevalent with increased PSS duration. Careful and regular monitoring of the thyroid function in PSS patients is advisable. PMID- 2109773 TI - Membrane Ig-cytoskeletal interactions. III. Receptor cross-linking results in the formation of extensive filamentous arrays of vimentin. AB - The proposed function of intermediate filaments is to provide a cell type specific structural framework that maintains cell shape and organelle distribution and mediates signal transduction through its connections with the plasma membrane and the nucleus. Vimentin is the intermediate filament protein expressed in B lymphocytes. Immunocytochemical analysis of the high salt-stable cytoskeletons from B cells stimulated with anti-Ig revealed an increased accumulation of vimentin in the cytoskeleton compared to nontreated controls. This increased accumulation of vimentin in the cytoskeleton was manifested by the organization of vimentin into extensive filamentous arrays (EFA) as viewed in the fluorescent microscope. In contrast to the effects of anti-Ig, activation of B cells with LPS did not induce the organization of vimentin into EFA. This suggested that signals unique to anti-Ig directed EFA formation. Immunocytochemical results were verified by biochemical analysis showing that vimentin was more abundant in isolated cytoskeletons from anti-Ig activated B cells, than cytoskeletons isolated from LPS-activated B cells. These observations established a relationship between increased content of vimentin in the cytoskeleton and the formation of EFA. By testing a wide variety of activating agents, we were able to correlate increased vimentin expression in the cytoskeleton to activating agents that cross-link membrane Ig. It appeared that treatment of B cells with LPS prohibited the induction of EFA by anti-Ig because cotreatment with both anti-Ig and LPS resulted in decreased vimentin accumulation in the cytoskeleton to a level less than that in resting cells. The significance of these results with regard to B cell biology is discussed. PMID- 2109774 TI - Membrane IgM and IgD molecules fail to transduce Ca2+ mobilizing signals when expressed on differentiated B lineage cells. AB - We have measured Ca2+ mobilization in a panel of B lineage cell lines after stimulation with anti-Ig to assess whether membrane Ig transduces a functional signal in cells that are representative of immature, mature, or terminally differentiated stages. For these studies, three transfected cell lines which express the same IgM molecule (300-19 microns lambda 36/8, K46-17 microns lambda, and J558L microns lambda 3) as well as two lines expressing an identical IgD molecule (K46 delta m2.6 and J558L delta m8.8) were used. Cross-linking of membrane Ig on IgM+ or IgD+ lymphomas (K46-17 microns lambda or K46 delta m2.6) resulted in a Ca2+ mobilization response that is similar to that seen in mature, resting B cells. Both intracellular release and extracellular influx of Ca2+ were observed. In contrast, ligation of membrane Ig on an IgM+ pre-B cell line (300 - 19 microns lambda 36/8) induced extracellular influx of Ca2+ but no detectable intracellular release. Finally, cross-linking of membrane Ig on IgM+ or IgD+ plasmacytomas (J558L microns 3 or J558L delta m8.8) or an IgD+ B cell hybridoma (B1.8.delta 1) expressing an endogenous Ig gene, did not result in a detectable Ca2+ mobilization response. Importantly, stimulation of cells with the GTP binding protein activator, aluminum fluoride, resulted in a comparable Ca2+ mobilization response in all cell lines. In view of the fact that aluminum fluoride induced a Ca2+ response in the terminally differentiated B cell lines, J558L microns 3, J558L delta m8.8, and B1.8.delta 1, it is likely that there is an alteration in the signal transduction cascade at some point proximal to GTP binding protein activation. This finding suggests that differentiation of the B cell is accompanied by the loss or alteration of one or more components that couple membrane Ig to subsequent signal transduction elements. Finally, it has previously been demonstrated that the IgM+ cell lines described above, express the recently described membrane Ig-associated protein, B34. Thus, it is apparent based on the fact that the J558L microns 3 cell line does not mobilize Ca2+ after stimulation with anti-Ig, that coexpression of B34 in association with membrane Ig does not constitute a functional receptor complex capable of activating GTP binding proteins that in turn regulate Ca2+ mobilization. PMID- 2109775 TI - Evidence for CD8-independent T cell maturation in transgenic mice. AB - Double-negative (CD4-/CD8-) T cells expressing the alpha/beta transgenic TCR from the 2C cell line (anti-H-2Ld) were examined in the periphery of animals whose MHC type produces positive, negative, or no selection for differentiation of the TCR on single positive (CD8+) cells. Regardless of the selection haplotype the CD4 /CD8- cells are capable of activation by anticlonotypic mAb indicating that negative selection does not inactivate the "forbidden" TCR. Rather, the lack of response to H-2Ld in the negative haplotype is likely to absence of CD8 required to produce a functional response to H-2Ld. The similarity of surface phenotype and functional activity of these CD4-/CD8- cells maturing in different haplotypes suggests they may arise by an alternative lineage which, unlike the dominant TCR alpha/beta pathway, does not require coexpression of CD4/CD8. PMID- 2109776 TI - Quantitative analysis of cytokine gene expression in rheumatoid arthritis. AB - Previous studies of the cytokine profile of rheumatoid arthritis (RA) have been primarily limited to the assessment of the levels of these mediators in synovial fluid (SF) or synovial tissues (ST) by biologic or immunologic assays. We have studied cytokine gene expression in RA by in situ hybridization of SF cells, enzymatically dispersed ST cells, and frozen sections of ST. RA ST cells (n = 7) were studied and a high percentage of cells hybridized to the following anti sense probes: IL-6 = 19 +/- 3.3%; IL-1 beta = 9.9 +/- 1.7%; TNF-alpha = 5.8 +/- 1.4%; granulocyte-macrophage-CSF = 2.2 +/- 0.8%; transforming growth factor-beta 1 = 1.3 +/- 0.2% (p less than 0.05 for each compared to sense probes). Similar results were found using osteoarthritis ST cells, although the percentage of cells expressing the IL-6 gene (7.1 +/- 2.5%) was significantly less in osteoarthritis compared to RA. RA ST cells did not significantly bind the IFN gamma probe (0.2 +/- 0.1% positive), although they were capable of expressing the IFN-gamma gene if stimulated with PHA. The OKM1+ population of ST cells (i.e., macrophage lineage cells) was greatly enriched for IL-1 beta and TNF-alpha, whereas the OKM1- population (lymphocytes, fibroblasts, and type B synoviocytes) was enriched for IL-6. The vast majority of cells expressing the IL-6 gene were non-T cells. Furthermore, hybridization to RA ST frozen sections localized IL-6 mRNA to the synovial lining layer, which is comprised of type A and type B synoviocytes. In contrast to the high level of cytokine gene expression observed in ST, SF cells did not hybridize significantly to any of the cytokine probes. If stimulated with LPS or PHA, SF cells expressed IL-1 beta or IFN-gamma genes, respectively. PMID- 2109777 TI - Regulation of macrophage activation by IL-3. II. IL-3 and lipopolysaccharide act synergistically in the regulation of IL-1 expression. AB - We have previously reported that IL-3, a cytokine produced by both Th1 and Th2 type CD4+ T cells, displays macrophage-activating potential. IL-3, like IFN gamma, readily induced functions related to Ag presentation (e.g., Ia and lymphocyte function-associated Ag-1 expression). However, in contrast to the response elicited by IFN-gamma, tumor cytotoxicity was not induced by IL-3. In this paper we have evaluated the capacity of IL-3 to regulate IL-1 expression. Our data demonstrate that although IL-3 alone was unable to induce the production of substantial IL-1 bioactivity in peritoneal exudate cells, it contributed synergistically to the induction of IL-1 bioactivity in the presence of suboptimal doses of LPS. It was of interest that IFN-gamma, which can also interact synergistically with LPS, was unable to complement the partial signals provided by IL-3 for the expression of IL-1 bioactivity, suggesting that IL-3 and IFN-gamma may be providing similar stimulatory signals in this respect. Our studies on the mechanism of synergy between IL-3 and LPS indicated that the effect of LPS did not appear to be mediated by the well-characterized LPS inducible cytokines of macrophage origin (i.e., IL-1, alpha and beta, TNF-alpha, and IL-6). The best characterized function of IL-3 is its multicolony-stimulating activity as a CSF; in this context we also studied granulocyte-macrophage CSF and noted that it behaves similarly to IL-3 in that it can synergistically contribute to IL-1 induction. A similar, but more dramatic induction of IL-1 synthesis in response to IL-3 was demonstrated by the P388.D1 murine macrophage cell line. The kinetics and the molecular mechanism of the response of P388.D1 to IL-3 indicate several unique features of IL-3-induced IL-1 expression: 1) IL-3 itself induced IL-1 mRNA expression, which was unaccompanied by substantial production of bioactivity, either cell-associated or secreted into the culture supernatant; 2) IL-3 synergized with suboptimal doses of LPS to induce not only heightened IL-1 mRNA levels but bioactivity as well; and 3) IL-3, when combined with LPS, altered the kinetics of IL-1 message and bioactive protein production in response to LPS: IL-3 and LPS induced an early release (3 to 7 h poststimulation) of the IL-1 protein as well as a second peak of mRNA and bioactivity (at 12 to 36 h), which was not observed in response to either IL-3 or LPS alone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2109778 TI - Deacylated lipopolysaccharide inhibits plasminogen activator inhibitor-1, prostacyclin, and prostaglandin E2 induction by lipopolysaccharide but not by tumor necrosis factor-alpha. AB - Bacterial LPS and TNF induce vascular endothelial cells to express a variety of response molecules. LPS that is partially deacylated (dLPS) by a human neutrophil enzyme blocks the ability of LPS, but not TNF, to augment one of these responses, the expression of endothelial cell surface molecules that promote neutrophil adherence (J. Exp. Med. 1987; 165:1393-1402). We show that dLPS can inhibit the ability of LPS, but not TNF, to elicit the expression of plasminogen activator inhibitor-1 (PAI-1), prostacyclin, and PGE2 by human umbilical vein endothelial cells. dLPS also prevented the accumulation of specific PAI-1 mRNA in response to LPS, but not to TNF. Neither the LPS- or TNF-induced expression of PAI-1 nor the dLPS inhibition of the LPS response was mediated by prostanoids. These results indicate that dLPS can specifically block a variety of endothelial cell responses to LPS and provide support for the hypotheses 1) that dLPS and LPS may interact with a common target molecule on or in endothelial cells, and 2) that dLPS, produced by enzymatic deacylation of LPS in vivo, could inhibit endothelial cell stimulation by LPS and thereby limit the host inflammatory response to invasive gram-negative bacteria. PMID- 2109779 TI - Expression of IgE from a nonrearranged epsilon locus in cloned B-lymphoblastoid cells that also express IgM. AB - During development, B lymphocytes have the ability to switch from synthesis of IgM to immunoglobulins of another isotype such as IgG, IgA, or IgE. This class switching mechanism has been shown to involve DNA rearrangement and concomitant deletion of intervening CH genes. In our report, an EBV-transformed B lymphoblastoid cloned cell line is described that simultaneously expressed and secreted both IgM and IgE. DNA analysis showed the (nonproductive) rearrangement of one allele to gamma and (productive) rearrangement of the other allele to mu. Germ-line arrangement of the C epsilon gene was preserved on both alleles. PMID- 2109780 TI - Production of interferon-gamma by in vivo tumor-sensitized T cells: association with active antitumor immunity. AB - The state of active immunity to Meth A fibrosarcoma in mice immunized with an admixture of Meth A cells and Propionibacterium acnes is associated with possession by the host of spleen cells capable of producing interferon-gamma (IFN gamma) upon in vitro restimulation with irradiated tumor cells. The ability of spleen cells from immunized mice to produce IFN-gamma in response to irradiated Meth A cells decays as active antitumor immunity is replaced by a state of immunological memory. The IFN-producing cells are L3T4+Ly2+, cyclophosphamide sensitive and radiosensitive T cells, as determined by their sensitivity to corresponding monoclonal antibodies and complement. The induction of IFN-gamma production by in vivo tumor-sensitized T cells is tumor specific, in that spleen cells from mice immunized against Meth A fibrosarcoma can produce IFN in response to irradiated Meth A cells but not in response to another syngeneic tumor M109 lung carcinoma. PMID- 2109781 TI - In vitro and in vivo effect of interleukin-2 on the 2',5'-oligoadenylate synthetase activity of peripheral mononuclear blood cells. AB - The in vitro and in vivo influence of interleukin-2 (IL-2) on 2',5' oligoadenylate (2-5A) synthetase activity and natural killer (NK) activity of peripheral mononuclear blood cells (PBMCs) was investigated. Incubation of PBMCs in vitro with IL-2 resulted in a considerable secretion of interferon-gamma (IFN gamma) and in a significant elevation of 2-5A synthetase activity, as well as NK activity. Neutralizing monoclonal anti-IFN-gamma antibodies inhibited the elevation of 2-5A synthetase activity, but not the IL-2-induced augmentation of NK activity. Additionally, 2-5A synthetase and NK activity of PBMCs was measured in a child with neuroblastoma that was treated with recombinant IL-2 by continuous intravenous application. During the treatment, NK activity against the NK-sensitive cell line K 562 and against autologous tumor cells was not augmented. However, a significant increase of 2-5A synthetase activity in PBMCs was observed during IL-2 treatment, whereas there was no detectable serum level of IFN-gamma. We conclude that measuring 2-5A synthetase activity in patients treated with IL-2 may be helpful in monitoring the immunomodulatory effects of IL 2 on immune effector cells. PMID- 2109782 TI - [The effect of PGI2 analogue on the warm ischemic changes in canine lung]. AB - The purpose of this study is to evaluate the effect of PGI2 analogue on the warm ischemic injury in the reimplantation model of the lung. Twenty-five mongrel dogs were subjected to this experiment in which the left thoracotomy and complete left hilar stripping were performed. The dogs were divided into 4 groups. The control group (8 dogs) did not have any medical treatment. I2 1 microgram group (7 dogs) received PGI2 analogue in the amount of 1 microgram/kg/min for 30 min during hilar dissection. I2 50 ng group (5 dogs) received PGI2 analogue in the amount of 50 ng/kg/min for 30 minutes. Heparin group (5 dogs) received 100 U/kg of heparin after hilar stripping. Then left, PA, PV, and Bronchus were clamped for 1 hour to make the left lung a warm ischemic state. To evaluate the function of the left lung subjected for a warm ischemia, right pulmonary artery was occluded for 10 minutes and PaO2, PaCO2, Qs/Qt, pulmonary artery pressure, pulmonary vascular resistance, thromboxane B2, and 6-keto-PGF1 alpha were measured. Two hours after reperfusion, pulmonary microangiography and histological investigation were performed. As a result of warm ischemia, PaO2 was 158 mmHg with 70% FiO2 1 hour after reperfusion in control group, whereas it was maintained at as high as 299 mmHg in I2 1 microgram group. PaCO2, Qs/Qt, pulmonary artery pressure, as well as the pulmonary vascular resistance were almost normal throughout the experiment in I2 1 microgram group, but they gradually elevated in control group during the experiments. In the other two groups these parameter are not so satisfactory as in I2 1 microgram group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109783 TI - Lipid screening in paediatrics for early detection of cardiovascular risks. AB - The purpose of the study was to try to detect at an early stage the important cardiovascular risk factors associated with increased concentrations of blood lipids, notably cholesterol. The trial was based on the screening of 102 families, including 219 children, 8-18 years of age and their parents. A group of young adults, 19-25 years of age, was included in the study. All subjects were derived from a paediatric practice. In addition to total cholesterol, VLDL-, LDL , HDL-cholesterol and apolipoproteins A-I and B were also measured. The study identified a significant number of school-children and adolescents with hyperlipidaemia, predominantly hypercholesterolaemias type II-A. There was a close relationship between their blood lipids and those of their parents. The study demonstrates the importance of including parents in studies of this kind. Total cholesterol proved to be a reliable parameter for screening. The value of apolipoproteins in such screening is discussed. PMID- 2109784 TI - Transthyretin--an explanation of "anomalous" serum thyroid hormone values in severe illness? AB - The following serum analytes were measured in 464 patients with defined carcinomas and other tumours as well as those with chronic obstructive lung disease and under regular haemodialysis, and in 261 healthy controls: thyrotropin (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine (fT4), thyroxine binding globulin (TBG) and transthyretin (TTR). The following ratios were constructed: fT4 x TTR, defined as the thyroxine availability index fT4/TTR, defined as the thyroid hormone compensation index 100 x T3/TBG as the free T3 index (fT3I) and fT3I x TTR, defined as the triiodothyronine availability index. Significantly elevated thyrotropin values (p = 0.05) were only found in patients with breast cancer when compared with age matched controls, although elevated T4 and fT4 values were found in all experimental groups except the haemodialysis patients (p less than 0.01). The thyroxine availability index and triiodothyronine availability index values were not significantly different from the age matched controls (greater than 60 a) in the cancer groups, showing that the transthyretin concentrations compensated for changes in fT4 or vice versa. These findings are reflected in the euthyroid thyrotropin values. The T4 and fT4 values in the dialysis patient group were significantly lower than in the age matched controls (p less than 0.01), while the transthyretin values were significantly higher (p less than 0.01), which accounted for the normal thyroxine availability index and euthyroid thyrotropin values. PMID- 2109785 TI - Unforeseen effect of thyroxine binding globulin when using the microencapsulated antibody method to determine free thyroxine (FT4): misleading results due to circulating unsaturated thyroxine binding globulin. AB - The effect of varying concentrations (0-52 mg/l) of purified thyroxine binding globulin (TBG) on the microencapsulated antibody method for free thyroxine was investigated. The results demonstrated that the free thyroxine values were strongly influenced by the concentration of thyroxine binding globulin in the samples. The standard curve could no longer be distinguished at a concentration of purified thyroxine binding globulin of 52 mg/l. In the clinical application, we observed that the values obtained using the microencapsulated antibody method were significantly higher than the expected values in patients receiving triiodothyronine treatment after total thyroidectomy (theoretically nil) and in patients with untreated primary hypothyroidism with negligible thyroxine (less than 12.9 nmol/l). These false positive values are considered to be due to the methodological problem mentioned above, i.e. the microcapsule membrane is not efficient and therefore must be improved. Consequently, any data based on this method should be interpreted with caution. PMID- 2109786 TI - A voltage-clamp analysis of gene-dosage effects of the Shaker locus on larval muscle potassium currents in Drosophila. AB - Mutations of the Shaker (Sh) locus of Drosophila reduce, eliminate, or otherwise alter a transient potassium current, IA, in muscle. Recent molecular studies indicate that the Sh locus produces several proteins by alternative splicing, but the relationships of the variety of Sh gene products to IA channels in the various excitable membranes still remain to be determined. In Drosophila, many enzymes have been shown to exhibit gene-dosage effects; their amounts vary in direct proportion to the number of structural genes present. We describe a physiological isolation of IA in larval muscle which allowed precise quantification of gene-dosage effects on IA in Sh heterozygotes and aneuploids. We found that doubling the number of Sh genes in aneuploids increased IA to twice that of normal, consistent with the notion that the Sh locus encodes the entire IA channel in larval muscle. We further examined heterozygous combinations of different Sh mutations for evidence of interactions among Sh gene products within the IA channel, which may yield clues to the possible subunit composition of the channel. Combinations among 5 Sh mutations plus their normal counterpart followed a simple gene-dosage effect; in each case the resulting IA was about the average of the homozygous currents, compatible with the notion of additive contributions from 2 independent populations of IA channels. Two additional Sh mutations caused pronounced departures from the simple dosage effect; the amplitude of IA in heterozygotes was significantly smaller than that expected from gene dosage, a strong dominant effect attributable to interactions among protein subunits. These contrasting observations may be accounted for by certain hetero- or homo multimeric arrangements of Sh products in the IA channel. PMID- 2109787 TI - Increasing intracellular free calcium induces circumferential contractions in isolated cochlear outer hair cells. AB - The relationship between intracellular free calcium and the motile responses of outer hair cells isolated from the guinea pig cochlea was examined. Calcium levels were modulated by the addition of the calcium ionophores ionomycin or A23187 to the incubation medium and monitored with the fluorescent calcium indicator fluo-3. In the presence of 1.25 mM external calcium, the application of either ionophore (10 microM) led to an increase in intracellular free calcium from 157 +/- 76 nM to 1200 +/- 500 nM within 30-60 sec. Concurrently, cells elongated by 1-2 microns, cell diameter decreased, and cell volume shrank by 269 +/- 220 microns 3 (5.0 +/- 4.1%). The reduction in diameter was most pronounced in the middle portion of the cell (4.4% +/- 4.2%), also evident in the apical region (3.1% +/- 4.8%) but not significant in the basal region near the nucleus. This response was observed in outer hair cells from basal and apical turns of the cochlea and was reversed when the cells were rinsed with calcium-free medium supplemented with 2 mM EGTA. Optical imaging of the cell membrane with the potentiometric dye 1-(3-sulfonatopropyl)-4-[beta] [2-(di-n-butylaminol)-6 naphthyl vinyl] pyridinium betaine during the elevation of intracellular calcium demonstrated features of contractility at the lateral cell membrane. A rise in intracellular calcium as well as the motile response was still observed after a 5 min exposure of the cells to a calcium-free solution (supplemented with 2 mM EGTA), indicating that the ionophore was also able to liberate calcium from intracellular sites. However, depletion of calcium stores through prolonged incubation of the cells in calcium-free medium (30-60 min) suppressed both the calcium signal and the cell response. The calmodulin inhibitors trifluoperazine and pimozide (30 microM) blocked the cell motility induced by ionomycin while they left the increase of intracellular calcium unaffected. These observations suggest that calcium-dependent circumferential contractions in outer hair cells are mediated by calmodulin. The application to the extracellular medium of putative neurotransmitters of the cochlear efferent system such as acetylcholine and GABA led to neither an increase in intracellular calcium nor a modification of cell shape. Therefore, these neurotransmitters may not be directly involved in calcium-induced contractions in outer hair cells. The circumferential contractions altered the stiffness of the plasma membrane and the turgor of the cell. Under normal conditions, changes in cell volume were inversely proportional to the osmotic pressure of the extracellular medium following van't Hoff's law.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2109788 TI - A productivity measure for nursing staff development. AB - Methods and measures to determine adequate productivity levels for nursing staff development are needed to demonstrate to an institution's administrators the quantitative contribution made by the nursing staff development department. This article describes a management utilization approach used to develop a rational, yet simple to calculate, productivity formula. The formula was refined through 5 years use in one setting and tested in several others. Detailed explanations, rationales, and calculations are provided to help staff development specialists further test this formula. PMID- 2109789 TI - The effect of protein-energy malnutrition and refeeding on the adherence of Salmonella typhimurium to small intestinal mucosa and isolated enterocytes in rats. AB - The adherence of fimbriated (Fim+) and nonfimbriated (Fim-) strains of Salmonella typhimurium to both isolated intestinal epithelial cells and intact intestinal mucosa of healthy and malnourished rats was investigated. Fim+ strains bound in significantly higher numbers than did Fim- strains to enterocytes isolated either from healthy or malnourished rats. Adherence to intact intestinal mucosa in situ was demonstrable with both Fim+ and Fim- bacteria, but Fim+ strains were preferred because they showed approximately twofold higher numbers of adhered bacteria compared to Fim- strains. Additionally, bacterial adherence to intact mucosa in situ was consistently higher in well-fed controls than in malnourished rats. Ultrastructural studies revealed marked cell destruction and lysis in malnourished rats, whereas no histological change was detected in the mucosa of control animals. These results suggest that malnutrition may lead to altered intestinal cell surfaces, thus increasing their susceptibility to infection through mechanisms that are different from adherence. PMID- 2109790 TI - Pulmonary function and clinical course in patients with cystic fibrosis after pulmonary colonization with Pseudomonas aeruginosa. AB - To evaluate the relationship between Pseudomonas aeruginosa colonization and the development of lung disease, we studied 895 patients who attended our cystic fibrosis clinic between 1975 and 1988. The prevalence of P. aeruginosa colonization was 82%. Patients who acquired P. aeruginosa in the first year of life had a similar 10-year survival rate (85%) to that in patients who were colonized between the ages of 1 and 7 years (87%), and to that in patients colonized after the age of 7 years (78%). One year before colonization, mean age, forced expiratory volume in 1 second (FEV1), forced vital capacity, and forced expiratory flow in the mid-expiratory phase were similar to those in a group of patients who remained free of P. aeruginosa. No significant change in pulmonary function variables could be demonstrated 1 year and 2 years after the colonization. The rate and duration of hospitalization did not increase in the years after P. aeruginosa colonization compared with the years before colonization. By the age of 7 years, the mean percentage of predicted FEV1 was lower by 10% in patients who were already colonized by P. aeruginosa compared with those who were not colonized (p less than 0.01). A similar reduction in FEV1 was observed at all ages from 7 to 35 years, but no precipitate rate of decline in FEV1 could be associated with P. aeruginosa colonization. We conclude that although P. aeruginosa colonization is associated with 10% lower lung function, it does not cause an immediate and rapid reduction, as has been previously reported. The clinical course and the pulmonary deterioration in cystic fibrosis after P. aeruginosa colonization is a gradual and variable process. PMID- 2109791 TI - Correlation of free oxygen radical-induced lipid peroxidation with outcome in very low birth weight infants. AB - Lipid peroxidation was measured in 19 very low birth weight infants with respiratory distress syndrome by quantitating ethane and pentane in expired air during the first 5 days postnatally. Despite high levels of inspiratory oxygen, the ethane and pentane output was low within the first 24 hours; thereafter it increased up to 100 and 30 fold, respectively. On days 1 to 3 there was no detectable correlation between lipid peroxidation and fractional inspiratory oxygen. However, on days 4 and 5, lipid peroxidation and fractional inspiratory oxygen showed a significant correlation. Maximal amounts of expired ethane and pentane were significantly higher for patients with a poor outcome (five deaths, six cases of bronchopulmonary dysplasia) than for those with good outcome (eight infants surviving intact) (p less than 0.01). The results imply a role for free oxygen radicals in the pathogenesis of life-threatening complications in the very low birth weight infant. PMID- 2109792 TI - Role of the source of phosphate salt in improving the mineral balance of parenterally fed low birth weight infants. AB - Because the monobasic potassium phosphate salt (monobasic) improves the solubility of calcium and phosphorus in amino acid plus dextrose solutions, compared with the current mixtures of monobasic plus dibasic salts (dibasic), we tested the bioavailability and clinical effects of monobasic in 16 parenterally fed low birth weight infants at standard (n = 8) and high levels (n = 8) of mineral intakes. A constant infusion of macronutrients and vitamin D was provided in a crossover design of two four-day periods. With standard intakes of calcium (35 mg/kg/day, 0.9 mmol/kg/day) and phosphorus (30 mg/kg/day, 1 mmol/kg/day), there was no difference between monobasic and dibasic regimens on balance data or plasma biochemical monitoring (calcium, phosphorus, pH, carbon dioxide pressure, base excess, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D). With the use of the monobasic regimen, the mineral intakes were doubled without precipitation in the infusate: calcium, 70 mg/kg/day (1.8 mmol/kg/day), and phosphorus, 55 mg/kg/day (1.7 mmol/kg/day). This led to increased apparent retention of both calcium (63 +/- 5 mg/kg/day, 1.58 +/- 0.12 mmol/kg/day) and phosphorus (52 +/- 4 mg/kg/day, 1.67 +/- 0.14 mmol/kg/day) compared with that for standard levels of mineral intake. The improvement of calcium-phosphorus balance was accompanied by more severe calciuria (9 +/- 2 mg/kg/day, 0.2 +/- 0.05 mmol/kg/day) and by metabolic compensation for an increased acid load. In addition to the possibility of exceeding the buffering capacity of the infant, this relative acidosis could also be evidence of improved bone mineralization. PMID- 2109794 TI - Fibrinolysis by tissue plasminogen activator in a child with pulmonary embolism. PMID- 2109793 TI - Successful treatment of neonatal aortic thrombosis with tissue plasminogen activator. PMID- 2109795 TI - Priorities for the use of finite resources. PMID- 2109796 TI - Carnitine deficiency in surgical neonates receiving total parenteral nutrition. AB - Carnitine plays a key role in the oxidation of fatty acids. Most solutions for parenteral nutrition do not contain carnitine. Because endogenous carnitine synthesis is insufficient in newborns, they are prone to developing a carnitine deficiency when they are dependent on total parenteral nutrition (TPN). Stimulated by the clinical observation of manifest clinical symptoms of carnitine deficiency in one patient, a study of 13 consecutive neonates who received TPN for over 2 weeks was begun. Their plasma carnitine levels before and during carnitine supplementation were determined. All patients had a carnitine intake far below the recommended minimal need of 11 mumol/kg per day. Although only three of them clearly showed clinical symptoms described as carnitine deficiency, carnitine supplementation for all neonates receiving TPN for over 2 weeks is recommended. PMID- 2109797 TI - Uptake kinetics of 2',3'-dideoxyinosine into brain and cerebrospinal fluid of rats: intravenous infusion studies. AB - The pharmacokinetics of 2',3'-dideoxyinosine (ddl) and its distribution to plasma, brain tissue and cerebrospinal fluid (CSF) were determined during and after 2-hr i.v. infusions of ddl (125 mg/kg/hr) in rats to define its specific pharmacokinetic parameters for subsequent studies of prodrugs designed to target this compound to the brain. Steady-state plasma concentrations of 50 micrograms/ml were obtained within 30 min after the start of infusions corresponding to a total clearance of 2.4 l/kg/hr. Postinfusion, ddl concentrations declined biphasically from plasma with alpha T1/2 = 3 min and beta T1/2 = 35 min. STeady-state concentrations of ddl in brain tissue and CSF were 2.6 micrograms/g in tissue and 0.81 microgram/ml in CSF, respectively. These values represent 4.7 and 1.5%, respectively, of the simultaneously determined plasma concentration. The estimated brain vascular space contribution to the observed brain uptake was 4.1%, obtained by least squares fitting of a compartmental pharmacokinetic model to the uptake data. Postinfusion, the elimination of ddl from the brain and CSF was significantly slower than from plasma, resulting in increased brain/plasma and CSF/plasma ratios after the infusions. The low steady-state brain/plasma or CSF/plasma ratios suggest rapid disappearance of ddl from the CNS relative to its rate of entry. These data indicate that ddl penetrates poorly into the brain. Thus, prodrugs with enhanced blood-brain barrier transport may improve the delivery of ddl to the brain. PMID- 2109798 TI - Chronic treatment with propranolol enhances the synthesis of prostaglandins E2 and I2 by the aorta of spontaneously hypertensive rats. AB - The effects of treatment with dl, d- or l-propranolol (subcutaneously for 1 week) on arterial blood pressure and on 6-keto prostaglandin (PG) F1 alpha (stable metabolite of PGI2) and PGE2 production by aorta, renal medulla and renal cortex were examined in spontaneously hypertensive rats. dl-Propranolol and l propranolol significantly (P less than .05) lowered blood pressures from 148 +/- 9/113 +/- 5 (n = 6) and 133 +/- 4/100 +/- 2 (n = 12) mm Hg to 112 +/- 3/80 +/- 3 and 121 +/- 3/81 +/- 3 mm Hg, respectively. Comparable treatment of spontaneously hypertensive rats with inactive d-propranolol was without effect. Basal immunoreactive (i) i6-keto-PGF1 alpha and iPGE2 production by isolated aorta, renal medulla and cortex was not different in vehicle compared to the dl propranolol-treated rats. In contrast, norepinephrine (1 microM)-stimulated synthesis of i6-keto PGF1 alpha and iPGE2 by the aorta in the dl-propranolol treated group was significantly (P less than .05) enhanced compared with the vehicle-treated group. Aortic i6-keto-PGF1 alpha and iPGE2 synthesis stimulated by norepinephrine in l-propranolol-treated rats was also significantly (P less than .05) higher than that observed in vehicle and d-propranolol-treated rats. dl Propranolol treatment did not alter norepinephrine-stimulated renal cortical or medullary i6-keto-PGF1 alpha or iPGE2 synthesis. Indomethacin (5 mg/kg i.p.) given on the last 2 days of dl-propranolol treatment, significantly inhibited aortic i6-keto-PGF1 alpha and iPGE2 production and blunted the antihypertensive effect of dl-propranolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109799 TI - Your CE topic (No. 111). Clinical application of transdermal drug delivery systems (Part II). PMID- 2109800 TI - Murine trophoblast cells are not killed by tumor necrosis factor-alpha. AB - Purified midgestation murine trophoblast cannot be killed by a variety of cell mediated effector mechanisms, with the exception of highly lytic effectors such as lymphokine-activated killer cells. We now report that this trophoblast population is also resistant to tumor necrosis factor (TNF)-alpha. PMID- 2109801 TI - Chloramphenicol-induced translational activation of cat messenger RNA in vitro. AB - The expression of the chloramphenicol-inducible chloramphenicol acetyltransferase gene (cat) of the staphylococcal plasmid pUB112 is regulated at the post transcriptional level. Previous in vivo analyses suggested that the antibiotic stalls ribosomes that are translating a regulatory leader peptide, and that a stalled ribosome activates the ribosome binding site of the acetyltransferase encoding sequence by opening an attenuating leader mRNA hairpin structure. To test this model, we used a Bacillus subtilis S-30 extract for an in vitro translation system and in vitro synthesized cat in RNAs. We showed that the leader portion of the cat transcript acts as a translational attenuator of cat gene expression in absence of chloramphenicol. The drug stimulates acetyltransferase synthesis by a leader mRNA-dependent activation of translation of the cat message. By using 5' end-labeled transcripts and employing the endogenous RNase activity of the S-30 extract we demonstrated that this activation is due to an antibiotic-induced stalling of a ribosome on cat leader mRNA. PMID- 2109802 TI - Application of office ultrasound in the management of the spinal cord injury patient. AB - The effectiveness of office ultrasonography of the bladder and kidneys to provide routine urological followup was assessed in the outpatient spinal cord injury clinic. A total of 86 asymptomatic spinal cord injury patients underwent office ultrasonography of the kidneys and bladder as part of the routine urological followup. There were 106 ultrasound scans performed. Of the patients 68 had a blinded excretory urogram for comparison, including 20 who underwent additional studies (computerized tomography scans of the abdomen and pelvis, and/or radiologist-performed ultrasound examinations of the kidneys and bladder). All 18 patients who underwent office ultrasound but not excretory urography each underwent computerized tomography scans of the abdomen and pelvis and/or radiologist-performed ultrasound examinations of the kidneys and bladder. Office ultrasound detected 5 of 6 kidney stones, 6 of 6 hydronephrotic kidneys, 5 of 7 renal masses (4 of 6 cysts and 1 of 1 renal tumor), 3 of 3 bladder stones and 3 of 3 bladder diverticula. Subtle changes of chronic renal infection noted on excretory urography in 4 patients were not detected on corresponding ultrasound scans but voiding cystourethrograms revealed no reflux, and comparison to prior studies confirmed that these renal units were stable. Outpatient ultrasonography performed by the urologist proved to be a cost-effective and sensitive screening examination for urological disorders in the spinal cord injury population. The technique is easily learned, well tolerated and indicated when further urological evaluation is required. PMID- 2109803 TI - Infectious diseases. PMID- 2109804 TI - [Diclonal gammopathy (IgG kappa, IgA lambda) with nephrotic syndrome terminating into IgA lambda myeloma after three years--report of a case]. AB - A 43-year-old man was admitted to our hospital because of legs edema and periorbital edema in Dec. 1983. Laboratory findings showed massive proteinuria (3.7 g/day), Bence Jones protein (BJP) in urine, and hypoproteinemia. Peripheral blood examinations were normal and a bone marrow aspiration showed hypocellularity with slight increase of monocytes and plasma cells. Serum immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda). Serum IgG was 1,690 mg/dl, IgA 379 mg/dl and IgM 160 mg/dl. No remarkable findings were obtained in bone survey, Ga-scintigraphy and rectal biopsy, and a diagnosis of diclonal gammopathy with nephrotic syndrome was made. In Aug. 1986, serum IgA started to increase rapidly with concomitant decrease IgG. He died of pneumonia due to pancytopenia in Dec. 1986, when serum IgG was 450 mg/dl, IgA 1,014 mg/dl, and IgM less than 39 mg/dl. Immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda) in serum and BEP (kappa, lambda), IgG (kappa) and IgA (lambda) in urine. An autopsy showed massive infiltration of myeloma cells which were positive for lambda light chain in bone marrow, suggesting a development of myeloma from a diclonal gammopathy in about 3 years. PMID- 2109805 TI - [Quantification and clinical significance of plasma apolipoproteins]. AB - The apolipoproteins are important determinants of the structure and metabolism of plasma lipoproteins. This paper reviews analytical methods and the clinical significance of plasma apolipoproteins. Our data on apo VLDL and apo HDL analysis using fast protein liquid chromatography (FPLC), monoclonal antibody against apo VLDL, especially apo C-I, apo B isoproteins (apo B-100 and apo B-48) and plasma apolipoprotein concentrations in the patients with diabetes mellitus and coronary heart disease, were described. Among the methods of apolipoprotein quantification, single radial immunodiffusion (SRID) is widely used in Japan and plasma concentrations of apo A-I, A-II, B, C-II, C-III and E in healthy adults were reported. We showed the usefulness of FPLC for fractionation of human apo VLDL and apo HDL. We prepared several monoclonal antibodies against human apo VLDL, especially apo C-I, which were used for quantification and structural analysis of plasma apo C-I. Apo B-48 was found to be a good metabolic marker of exogenous lipoproteins (chylomicron and chylomicron remnant) and apo B-48 containing lipoproteins were increased in the poorly controlled diabetic patients. PMID- 2109806 TI - [Evaluation of plasma tissue plasminogen activator (I-PA) levels in patients with liver diseases]. AB - Previous studies have demonstrated that plasma tissue plasminogen activator (t PA) level was elevated in patients with liver disease. In this study, t-PA antigen levels were investigated in patients with acute hepatitis (AH; N = 12), chronic hepatitis (CH; N = 8), compensated liver cirrhosis (CLC; N = 40), decompensated liver cirrhosis (DLC; N = 23) and hepatocellular carcinoma (HCC; N = 35). The increased t-PA levels (higher than 14 ng/ml) were found in 33% (4/12) of AH on the early hospital days, 25% (2/8) of CH, 45% (18/40) of CLC and 91% (21/23) of DLC, and 60% (21/35) of Hcc cases. In patient with LC, the correlations between t-PA levels and serum total bilirubin (T.Bill) and hepatic synthetic functions were investigated. The results were that the t-PA levels correlated positively with T. Bil and negatively with liver synthetic functions such as albumin, protein C and choline-esterase, indicating that t-PA increased almost in proportion to the deterioration of hepatic function. Serial determination of t-PA in patients with HCC treated by transcatheter arterial embolization (TAE) revealed that TAE failed to normalize the t-PA levels. In one case of HCC complicated with disseminated intravascular coagulation (DIC), t-PA showed a marked increase at acute phase of DIC and subsequent decrease after the successful treatment for DIC by gabexate mesilate (FOY) infusion. These results suggest that increased t-PA in liver disease is due mainly to deterioration of hepatic function, and that secondary fibrinolytic state, such as DIC, is also a contributing factor. PMID- 2109807 TI - [Use of the CO2 laser in the surgical treatment of complicated echinococcosis of the liver]. AB - The article discusses experience in the use of high-energy CO2 laser in the treatment of 108 patients with complicated forms of echinococcosis of the liver. The diagnostic efficacy of instrumental methods of examination is determined. The most informative are ultrasonic echolocation (96.8%) and computered tomography (100%). They allow exact localization of the cyst, which is important in the choice of the operative approach. The use of the laser for excising the fibrous capsule and treating the residual cavity makes is possible to: abandon the traditional methods for completing echinococcectomy (drainage of the residual cavity, marsupialization, capitonnage), exclude suppuration of the residual cavity, reduce markedly the period of the patient's hospitalization. PMID- 2109808 TI - [Use of laser radiation in proctology (review of the literature)]. PMID- 2109809 TI - [Nitroglycerin]. PMID- 2109810 TI - [Etiology, clinical aspects and therapy of acute idiopathic polyradiculoneuritis (Guillain-Barre-syndrome)]. PMID- 2109811 TI - Effect of aloes on blood glucose levels in normal and alloxan diabetic mice. AB - The acute and chronic effects of the exudate of Aloe barbadensis leaves and its bitter principle were studied on plasma glucose levels of alloxan-diabetic mice. Aloes was administered orally, 500 mg/kg, and the bitter principle was administered intraperitoneally, 5 mg/kg. The hypoglycemic effect of a single oral dose of aloes on serum glucose level was insignificant whereas that of the bitter principle was very highly significant and extended over a period of 24 h with maximum hypoglycemia observed at +8 h. In chronic studies, aloes was administered twice daily and the bitter principle was administered once a day for 4 days. The maximum reduction in plasma glucose level was observed at the 5th day in both cases. The hypoglycemic effect of aloes and its bitter principle may be mediated through stimulating synthesis and/or release of insulin from the beta-cells of Langerhans. PMID- 2109812 TI - [Primary antiphospholipid syndrome: study of 27 patients]. AB - The clinical and biological features of a series of 27 patients with the recently described primary antiphospholipid syndrome are reported. Most of them belonged to a cohort of 90 patients who were carriers of lupus anticoagulant, which had been detected in the systematic evaluation of prolonged activated partial thromboplastin times in our hospital. Since the diagnosis they underwent a prospective protocol of follow up, with a peak follow up period of 9 years. The mean age of the 27 patients was 40.8 years and there were virtually no differences between sexes. Venous thrombosis was the most common clinical finding (16 episodes in 14 of the 27 patients). The most prevalent laboratory findings were lupus anticoagulant and IgG anticardiolipin antibodies. PMID- 2109813 TI - [Primary prevention of arteriosclerosis: cost-efficiency ratio in the determination of blood cholesterol]. AB - Serum cholesterol, triglyceride, apoprotein Al and B, low-density and hig-density lipoprotein (LDL, HDL) cholesterol levels were quantitated, in two or more consecutive sample collections, in 289 middle aged males to assess the potential for misclassification of dyslipemia, according to the Sociedad Espanola de Arteriosclerosis and the USA National Cholesterol Education Program guidelines. They were grouped according to serum cholesterol values (less than 5.17 mmol/l, between 5.17 mmol/l and 6.17 mmol/l, and greater than 6.17 mmol/l) and misclassification was arbitrarily identified with different levels of the considered parameters. With cholesterol less than 5.17 mmol/l, misclassification was identified in 18.2% of the subjects, mainly with hypertriglyceridaemia or low HDL-cholesterol values. With cholesterol greater than 6.17 mmol/l there is a clear misclassification although obviated partially by the usual performance of complete routine lipoprotein analysis. Potential for misclassification is more evident when cholesterol was between 5.17 mmol/l and 6.17 mmol/l. To avoid such misclassification, HDL and LDL-cholesterol and serum cholesterol and triglyceride values should be measured in all subjects. Some data on the total cost in a general population screening are also presented; cost that on the author's opinion might be better invested under the control of a centralized institution. PMID- 2109814 TI - Misoprostol: discovery, development, and clinical applications. AB - Misoprostol is a synthetic 15-deoxy-16-hydroxy-16-methyl analog of PGE1, and the first prostaglandin to be registered for the treatment of peptic ulcer disease. Misoprostol is a safe and well-tolerated drug that exerts potent gastric antisecretory effects and mucosal protective actions on the gastric and duodenal mucosa. In a dosage of 800 micrograms daily in two or four divided doses, misoprostol produced rates of complete ulcer healing in both gastric and duodenal ulcer patients significantly superior to placebo and comparable to H2 receptor antagonists. The major adverse effect is diarrhea in about 10% of patients, but this is usually mild and self-limiting. Misoprostol possesses uterotonic activity and should not be used in pregnant women or those who wish to become pregnant. Misoprostol effectively heals and prevents NSAID-induced gastropathy, a therapeutic need previously unserved. Due to its mucosal protective properties, misoprostol may have advantages over antisecretory drugs in the compromised patient who is a chronic smoker or alcohol user, in refractory duodenal ulcer patients, in recurrent ulcer, and in emergency use for acute upper GI bleeding. Misoprostol's tissue-protective effects may also extend to other therapeutic areas. PMID- 2109815 TI - [LHRH analogs versus orchidectomy in prostate cancer]. PMID- 2109816 TI - HTK-solution (Bretschneider) for human liver transplantation. First clinical experiences. AB - The cardioplegic HTK-solution (Bretschneider) has not been used in human liver transplantation as yet. Herein the first results obtained from 14 patients with HTK-preserved liver grafts are presented. The suitability of HTK-solution could be shown. All grafts functioned primarily except one, where initial non-function was obviously due to donor reasons. The early postoperative peak values of transaminases as a sign of ischemic damage were average and similar to the values of other flushout solutions. Using HTK primary function could be achieved even in livers prospectively assessed as only of fair quality, and livers with poor donor function tests (MegX) functioned from the beginning. HTK-solution therefore seems to allow widening of the acceptance criteria for donor livers. It was not the aim of this trial to extend cold ischemic time, but 3 livers with 11 h and 12 h 25 showed immediate function. How far cold ischemic time can be extended is a still open question. All livers were rapidly cooled and homogeneously flushed out due to the low viscosity of HTK-solution. All livers had a soft consistency after perfusion indicating a low degree of cell edema. HTK therefore is an effective solution for liver preservation. PMID- 2109817 TI - Oral ofloxacin as treatment of malignant external otitis: a study of 17 cases. AB - Seventeen patients with malignant external otitis were treated with oral ofloxacin. Their mean age was 69 years. Seven of the patients were diabetic. Pseudomonas aeruginosa, sensitive to ofloxacin (Kirby-Bauer method, inhibition zone greater than or equal to 22 mm), was isolated from the external auditory canal in all patients. Ofloxacin (200 mg b.i.d.) was given to the patients for 12 to 39 days. Two patients also received additional parenteral antibiotic therapy. Subjective and objective improvement occurred in all patients during treatment, and complete resolution was documented in all patients, with one exception. Only one patient suffered recurrence 2 weeks after discontinuation of antimicrobial therapy. The results of our study suggest that oral ofloxacin is an effective treatment for malignant external otitis caused by Pseudomonas aeruginosa. PMID- 2109818 TI - Pharmacokinetic analysis of the plasma disappearance of ovine follitropin and analogues in the male rat. AB - Ovine follitropin (oFSH) and its chemically deglycosylated (DG) or the asialo analogue were injected as a single bolus (2.5 micrograms) to intact mature male rats and plasma levels measured by radioimmunoassay. Semi-logarithmic plots of the plasma disappearance curves were all biphasic. For all substances tested, the data were best fitted to a biexponential equation and the following parameters were calculated: the half-lives of the distribution and elimination phases and the metabolic clearance rate (MCR) at steady state. It was found that the distribution phase of oFSH was much slower than for deglycosylated (DG) alpha + beta recombinant, DG-oFSH and asialo-oFSH. The elimination half-lives for asialo oFSH and DG alpha + beta recombinant were much shorter than for oFSH and DG-oFSH. oFSH had the lowest MCR, followed by DG alpha + beta, DG-oFSH and asialo-oFSH. This study clearly shows that sugar residues internal to sialic acid also play a significant part in the clearance of the hormone. PMID- 2109819 TI - Production and partial purification of a gonococcal growth inhibitor produced by a strain of Neisseria meningitidis isolated from a homosexual man. AB - A Neisseria meningitidis strain isolated from the oropharynx of a homosexual man was shown to produce antigonococcal activity in vitro. A production method, on solid medium, was developed which yielded a soluble activity. The activity was detected at the end of logarithmic growth phase and the maximum activity was reached after 24 h of incubation. The antigonococcal substance was purified more than 300 times by ammonium sulphate precipitation, gel filtration on Ultrogel AcA 54, and chromatography on DEAE-Sephacel. The molecular weight of the inhibitory substance, estimated by molecular filtration, was 29 X 10(3) daltons. The partially purified inhibitor showed two major bands, 32 and less than 12.5 X 10(3) daltons by sodium dodecyl-sulphate polyacrylamide electrophoresis. The chemical nature of the inhibitor is probably proteic on the basis of trypsin sensitivity and the absorbance spectrum. PMID- 2109820 TI - Costs of magnetic resonance imaging in public hospitals. PMID- 2109821 TI - [Parenteral nutrition at home. Indications, implementation and experiences]. PMID- 2109822 TI - Gonadal function after 12-Gy testicular irradiation in childhood acute lymphoblastic leukaemia. AB - Gonadal function was assessed in 15 boys with acute lymphoblastic leukaemia (ALL) who had received testicular irradiation. The dose to the testes was 12 Gy in 12, 15 Gy in 1, and 24 Gy in 2 cases. All of those who had received 12 or 15 Gy had normal Leydig cell function, although high levels of gonadotropins suggest subclinical Leydig cell damage. The 2 who had 24 Gy had Leydig cell failure. All who were old enough to produce a semen specimen were azoospermic. PMID- 2109823 TI - [The correlation between the derivatives of the arachidonic acid cascade and oral pathology. A review of the literature]. AB - The effects of several metabolites deriving from the arachidonic acid cascade on oral tissues are reviewed. These include the effects on the pulp, tissues and gingiva, and on the development of radicular cysts and epithelial tumours of the oral cavity. PMID- 2109824 TI - Mass sociogenic illness in a day-care center--Florida. PMID- 2109825 TI - State-specific changes in cholesterol screening and awareness--United States, 1987-1988. PMID- 2109826 TI - Follicle-stimulating hormone regulation of androgen-binding protein messenger RNA in sertoli cell cultures. AB - FSH plays an important role in testicular Sertoli cell differentiation and function in spermatogenesis. Previous studies using rat androgen-binding protein (ABP) as a marker of FSH action on Sertoli cells have demonstrated in vivo and in vitro regulation of ABP. We now have extended these studies to examine FSH regulation of ABP mRNA using Northern blot hybridization. In the immature rat testicular ABP mRNA [1.7- and 2.3-kilobase (kb) species] increased with age and reached a maximum 20 days postpartum, coincident with an increased plasma FSH concentration. To determine the direct effect of FSH on Sertoli cells, we examined ABP mRNA in vitro. In Sertoli cell-enriched cultures FSH was found to maintain the major 1.7-kb ABP RNA transcript level over 5 days of treatment in a dose-dependent manner, whereas in the absence of FSH, ABP mRNA declined with time in culture. The ABP mRNA maintenance by FSH was accompanied by higher concentrations of secreted immunoreactive ABP, which declined in the absence of FSH. This FSH effect on ABP mRNA and secreted ABP was mimicked by the cAMP analog (Bu)2cAMP. After the decline of ABP mRNA during culture, administration of FSH did not result in a detectable increase in the 1.7-kb ABP mRNA within 3 days, whereas cAMP and c-fos mRNA were rapidly induced within 15 min. On the contrary, the level of the minor hybridizing ABP mRNA (2.3 kb) was altered by FSH, indicating differential regulation of the 1.7- and 2.3-kb hybridizing species. Also, after FSH deprivation, tissue plasminogen activator and inhibin alpha mRNA were substantially increased within 6 h of FSH treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109827 TI - Inhibition of somatotroph growth and growth hormone biosynthesis by activin in vitro. AB - Activin-A, a homodimeric protein composed of two inhibin beta A-subunits, was first isolated from gonadal fluids based upon its ability to stimulate FSH secretion and biosynthesis, but was also observed to suppress GH secretion. The present report describes the effects of activin on the biosynthesis of GH and the proliferation of pituitary somatotrophs. In pituitary cells cultured in the presence of 0.7 nM activin for 3 days, GH secretion was decreased by 50% compared to the control value. Inhibition of GH biosynthesis, measured by quantitative immunoprecipitation of [35S]methionine-labeled cells, could be observed after 24 h of activin treatment, and maximal (70%) inhibition of GH biosynthesis was observed after 3 days. Activin inhibited basal as well as GH-releasing factor (GRF)-, glucocorticoid-, and thyroid hormone-stimulated GH biosynthesis. Inhibin, which is known to reverse the effect of activin on FSH secretion, did not reverse the effect of activin on GH biosynthesis. Treatment of somatotrophs with activin for 3 days completely inhibited the growth-promoting effect of GRF on somatotrophs. However, no effect of activin on GRF-stimulated expression of the c fos protooncogene was observed. These data demonstrate that activin, in addition to its stimulatory effect on FSH secretion, is able to inhibit both expression of GH and growth of somatotropic cells. PMID- 2109828 TI - Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy. AB - Albright's hereditary osteodystrophy is an autosomal dominant disorder characterized by a short stature, brachydactyly, subcutaneous ossifications, and reduced expression or function of the alpha subunit of the stimulatory G protein (Gs alpha) of adenylate cyclase, which is necessary for the action of parathyroid and other hormones that use cyclic AMP as an intracellular second messenger. We identified a unique Gs alpha protein in erythrocytes from two related patients with Albright's hereditary osteodystrophy and reduced Gs alpha bioactivity. The Gs alpha variant was recognized by a carboxyl terminal-specific Gs alpha antiserum but not by polyclonal antiserums specific for the amino terminus of Gs alpha. To investigate the molecular basis for this structurally abnormal Gs alpha protein, we studied the Gs alpha gene by restriction-endonuclease analysis. DNA from the two patients had an abnormal restriction-fragment pattern when digested with Ncol, which was consistent with loss of an Ncol restriction site in exon 1 of one Gs alpha allele. Amplification of a 260-base-pair region that includes exon 1 of the Gs alpha gene and direct sequencing of the amplified DNA revealed an A-to-G transition at position +1 in one Gs alpha allele from each of the two patients. This mutation converts the initiator ATG (methionine) codon to GTG (valine), blocking initiation of translation at the normal site. Translation of the abnormal Gs alpha messenger RNA would result in the synthesis of a truncated Gs alpha molecule lacking the amino terminus. We conclude that in at least some patients with Albright's hereditary osteodystrophy, the disease is caused by a single-base substitution in the Gs alpha gene and is thus due to an inherited mutation in a human G protein. PMID- 2109829 TI - Albright's hereditary osteodystrophy and defective G proteins. PMID- 2109830 TI - Biotechnology patents. Genentech wins round two. PMID- 2109831 TI - Sex determination compared in Drosophila and Caenorhabditis. AB - Fruitflies and nematodes show many similarities in the general organization of the gene networks that control sexual dimorphism and dosage compensation. In contrast, the underlying molecular mechanisms appear to be very different in these two species. Developmental processes such as sex determination need not be strongly conserved in evolution. PMID- 2109833 TI - Biological warfare. Gruinard Island handed back. PMID- 2109832 TI - Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels. AB - Calcitonin gene-related peptide (CGRP) is a 37-amino-acid peptide produced by alternative processing of messenger RNA from the calcitonin gene. CGRP is one of the most potent vasodilators known. It occurs in and is released from perivascular nerves and has been detected in the blood stream, suggesting that it is important in the control of blood flow. The mechanism by which it dilates arteries is not known. Here, we report that arterial dilations in response to CGRP are partially reversed by blockers of the ATP-sensitive potassium channel (K(ATP)), glibenclamide and barium. We also show that CGRP hyperpolarizes arterial smooth muscle and that blockers of K(ATP) channels reverse this hyperpolarization. Finally, we show that CGRP opens single K+ channels in patches on single smooth muscle cells from the same arteries. We propose that activation of K(ATP) channels underlies a substantial part of the relaxation produced by CGRP. PMID- 2109834 TI - BSE. Britain not alone in its predicament? PMID- 2109835 TI - Heat-shock proteins DnaK and GroEL facilitate export of LacZ hybrid proteins in E. coli. AB - The use of lacZ gene fusions, producing a hybrid protein containing an amino terminus specified by a target gene fused to the functional carboxy terminus of beta-galactosidase, has facilitated the study of protein targeting in various organisms. One of the best characterized fusions in Escherichia coli is phi(lamB lacZ)42-1(Hyb), which produces a hybrid protein with the signal sequence and 181 N-terminal amino acids of the exported protein LamB, attached to LacZ. In common with other LacZ hybrids, the LamB-LacZ(42-1) protein is poorly exported from E. coli, conferring a Lac+ phenotype. beta-Galactosidase activity decreases markedly when cells producing the LamB-LacZ protein are grown at 42 degrees C or when a heat-shock response is induced at lower temperatures by overproducing heat-shock factor RpoH3, indicating the LacZ hybrids are being efficiently targeted to the cell envelope. We now report that the heat-shock proteins DnaK and GroEL can, in sufficient amounts, decrease beta-galactosidase activity and facilitate the export of lacZ-hybrid proteins. PMID- 2109836 TI - Schistosomiasis. The mouse that wasn't immune. PMID- 2109837 TI - A binding site for the T-cell co-receptor CD8 on the alpha 3 domain of HLA-A2. AB - Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 alpha-chain binds to the alpha 3 domain of HLA-A2.1. Three clusters of alpha 3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation. PMID- 2109838 TI - A nurse-run business to improve health care for nursing home residents. AB - The costs of health care for the rapidly growing segment of our population over age 75 are staggering. EverCare is a nurse-run business that seeks to improve cost-effectiveness and quality of health care for nursing home residents enrolled in a health maintenance organization. PMID- 2109839 TI - Local administration of flurazepam has different effects on dopamine release in striatum and nucleus accumbens: a microdialysis study. AB - The action of local administration of flurazepam on extracellular levels of dopamine (DA) and its metabolites 3,4 dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the anterior striatum and medial nucleus accumbens have been investigated using microdialysis. Flurazepam (10 microM), administered through the perfusion medium for 20 min, reduced levels of DA in dialysates from the nucleus accumbens by 60% while the same concentration of the drug had no effect on levels of DA in perfusates from the striatum. Pretreatment with the benzodiazepine antagonist Ro 15-1788 (flumazenil) or with picrotoxin, a drug which blocks the GABAA receptor-associated chloride channel, inhibited the effect of flurazepam on levels of DA in the nucleus accumbens, which suggests that the effect was mediated by the multimolecular GABAA/benzodiazepine receptor complex. Administration of flurazepam had little effect on the two metabolites of DA, DOPAC and HVA, in either the nucleus accumbens or striatum. The inverse partial benzodiazepine agonist, FG 7142, had no significant action on the release of DA in the nucleus accumbens. These results suggest that the dopaminergic projection to the nucleus accumbens is more sensitive to benzodiazepine-induced inhibition than the projection to the striatum. PMID- 2109840 TI - Efficacy of tissue plasminogen activator in the lysis of thrombosis of the cerebral venous sinus. AB - Therapy for thrombo-occlusive disease of the cerebral venous sinuses remains controversial. Although several thrombolytic agents, such as urokinase and anticoagulants, are recommended for treatment, major significant risks include cerebral hemorrhage, especially in patients with venous infarction. Tissue plasminogen activator (tPA) has shown a high affinity for fibrin-bound plasminogen, while exhibiting a low affinity for circulating plasminogen. The purpose of this study was to evaluate this drug for use in cerebral sinus thrombo occlusive disease. Eleven adult male rabbits were chosen as experimental animals. All animals underwent microsurgical dissection of their major dural venous sinuses. Direct compression was used to form a thrombus within the sinus. The presence of significant venous thrombosis was confirmed radiographically by iohexol sinography. Subsequently, tPA was delivered systemically via the marginal ear vein at a dose of 3000 units/h; the result was total lysis of the clot documented by a sinogram 1 hour after the drug was administered. Postmortem pathological examination confirmed total lysis in seven of eight animals. One animal showed partial retained clot fragments. No significant coagulopathic state was observed. In three control animals, saline was infused without clot lysis. We conclude that tPA is a highly effective agent for the lysis of acute induced venous sinus thrombosis in an experimental model. PMID- 2109841 TI - Relationship of invasiveness to proliferating activity and to cytoskeletal protein production in human neuroepithelial tumors maintained in an organ culture system: use of human cortex and dura as supporting matrices. AB - The proliferation and invasiveness of cultured human neuroepithelial tumors were studied. A human malignant astrocytic glioma cell line (U-251 MG) and a medulloblastoma cell line (D283 Med) were maintained for 3 weeks in an organ culture system using adult human brain cortex, dura mater, or Gelfoam sponge as growth matrices. The cells were labeled with bromodeoxyuridine (BrdU) at different time points, and immunohistochemistry was performed for BrdU, glial fibrillary acidic (GFA) protein (in U-251 MG), and neurofilament (NF) protein (in D283 Med). In the U-251 MG line, the cells grew successfully in each matrix, forming a fibrillated solid area and a peripheral zone of invasion. The labeling index (LI) expressed as the percentage of BrdU-labeled cells and the percentage of GFA protein-positive cells in the two zones of the explants were analyzed. The LIs in all cultures were significantly higher in the peripheral than in the central zones. On the other hand, the percentage of GFA protein-positive cells in each matrix was greater in the central zone than in the periphery. The LI was inversely correlated with the percentage of GFA protein-positive cells over the areas counted in each growth matrix. GFA protein production in cells grown on cortex and on dura mater was significantly higher than that in cells grown on Gelfoam. In the D283 Med line, the cells formed an aggregated zone, with peripheral cells infiltrating the Gelfoam. This line showed poor growth on human cortex. Cells grown on the dura demonstrated an LI similar to that on Gelfoam, and cells often infiltrated the dura.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109842 TI - Low yield in the diagnostic evaluation of transient ischemic attacks. AB - Among 163 patients presenting with the clinical features of a TIA, extensive testing identified only 2 patients with nonatherosclerotic causes. We conclude that most patients with a TIA have atherosclerotic vascular disease and that screening tests for other etiologies have a low yield. PMID- 2109843 TI - Flow quantification in the superior sagittal sinus using magnetic resonance. AB - To date, the intracerebral veins and venous sinuses have not been amenable to noninvasive study. We describe a magnetic resonance (MR) technique using "bolus tracking" for rapid imaging and measurement of cerebral venous flow. We specifically applied the technique to the superior sagittal sinus, but it can be used for evaluation of other cerebral venous structures. In 10 healthy subjects and 21 patients referred for MR brain studies, mean flow was 420 ml/min. There was a significant inverse correlation between blood flow and age. There were dynamic changes in cerebral blood flow (CBF) during hyperventilation and hypercapnia. Since the cerebral cortex drains almost exclusively to the superior sagittal sinus, these flow measurements represent an index of global CBF. MR flow quantification provides a new means for assessing dynamic changes in CBF, and may prove useful for monitoring the effects of various disease processes and pharmaceutical agents on CBF. PMID- 2109844 TI - Acute CNS infection by Trypanosoma cruzi (Chagas' disease) in immunosuppressed patients. AB - Acute CNS involvement by Trypanosoma cruzi is uncommon. We report 2 immunosuppressed patients, 1 adult who developed an acute meningoencephalitis, and 1 child who presented with the tumor-like form of the disease. Both patients acquired the disease through blood transfusion. Blood donors migrating from endemic areas can transmit the disease in nonendemic countries if they are not routinely screened for antibodies to T cruzi. PMID- 2109845 TI - Spinal c-fos induction by sensory stimulation in neonatal rats. AB - C-fos immunocytochemistry was used to investigate the functional connectivity between primary afferent nociceptive fibres and second-order neurons in the spinal cord of the anaesthetised neonatal rat. Subcutaneous injection of 50 mg/kg capsaicin potently induced c-fos in the spinal cord on the first postnatal day (P1), whilst plantar injection of dilute formalin was much less effective until P3. In contrast with the adult, there was no c-fos response of the neonatal rat spinal cord to cutaneous application of the C-fibre irritant, mustard oil. It is concluded that spinal c-fos expression induced by noxious sensory stimulation can occur before the development of mature functional synaptic contact with first order neurones. PMID- 2109846 TI - A cost effectiveness analysis of the treatment of end stage renal failure. AB - An economic evaluation of continuous ambulatory peritoneal dialysis (CAPD), home haemodialysis, incentre haemodialysis and transplantation was carried out using cost effectiveness analysis to evaluate the cost per life year saved. The probability that a person with end stage renal failure would change treatment modalities was used to calculate an average five year treatment profile. The present value of the cost per life year saved (expressed in 1988 $NZ) was $35,270 for incentre dialysis, $28,175 for home haemodialysis, $26,390 for CAPD at Middlemore Hospital, $25,395 for CAPD at Auckland Hospital and $18.463 for transplantation. This ranking was unchanged after various sensitivity analyses. This apparent ranking of the cost effectiveness of the different modalities cannot, however, be used to support a decrease in haemodialysis in favour of an increase in transplants and CAPD until marginal cost factors have been studied. It must also be recognised that social and medical characteristics define which treatments are appropriate for any patient so that the different modalities are not perfect substitutes for each other. PMID- 2109847 TI - FY91: ashes to ashes. PMID- 2109848 TI - Birthweight: a predictor of nursing care needs. PMID- 2109849 TI - Use of the carbon dioxide laser in the management of orbital plexiform neurofibromas. AB - We present one of three cases in which we have used the carbon dioxide laser to successfully perform subtotal surgical removal of plexiform neurofibromas of the lid and orbit. PMID- 2109850 TI - Concepts of fluid therapy in diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma. AB - Despite many advances in the overall treatment of type I diabetes mellitus during the last few years, no major advance has been made in decreasing the mortality rate of diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic coma. A major concern in both of these disease states is the development of cerebral edema during treatment. The guiding principles of therapy in both disease states are rehydration, electrolyte replacement, insulin therapy, and treatment of any underlying illnesses. If the patient is hypotensive, therapy begins with colloid or normal saline administration to support blood pressure. Fluid and electrolyte deficits should be calculated and replaced during 48 hours. Low-dose insulin therapy is employed for treatment of hyperglycemia. Neurologic function should be carefully monitored and mannitol administered if a change in neurologic function occurs. PMID- 2109851 TI - Parenteral nutrition, and fluid and electrolyte therapy. AB - The provision of fluid and electrolytes during parenteral nutrition can be a challenge in the malnourished child or the child with complicating illnesses. The practitioner using the basic concepts of maintenance and deficit therapy--in this case for calories--must adapt his or her therapy to the expansion of the intracellular as well as the extracellular fluid compartment. Impairment of other organ systems further complicates the ability to deliver therapy. Careful monitoring and individually tailored solution will provide adequate caloric fluid and electrolyte therapy during parenteral nutrition in children. PMID- 2109852 TI - Home self-administration of intravenous immunoglobulin therapy in children. AB - Twelve children with primary immunodeficiency, aged 2 to 17 years (mean +/- 1 SD = 9.8 +/- 5.3), were enrolled in a 9-month study to evaluate the feasibility and safety of home self-infusion of intravenous immunoglobulin (IVIg). An initial 2 month training and supervisory period was followed by a 6- to 7-month period during which the children or their parents infused IVIg in a home setting. Eight children received an average dose of 204 +/- 12 mg/kg every 2 weeks, two children received a dose of 400 mg/kg every month, and an additional two children received 240 to 250 mg/kg every 10 days. Peak and trough levels varied from 946 +/- 20 mg/dL and 627 +/- 16 mg/dL, respectively, in children receiving IVIg every 2 weeks. The peak-trough values for the children receiving IVIg every month were 1105 +/- 94 mg/dL and 457 +/- 78 mg/dL, while those of children receiving IVIg every 10 days were 840 +/- 24 mg/dL and 553 +/- 109 mg/dL. A total of 224 infusions were administered, with only two minor reactions occurring (reaction rate of 0.9%). There was no difference in the frequency of infections and antibiotic use during the study compared with the previous phase. The results demonstrate that home self-infusion of IVIg in children is safe and feasible. PMID- 2109853 TI - Actinomycosis manifesting as an acute painless lump of the jaw. PMID- 2109854 TI - [Maternal and child care in the new economic system]. PMID- 2109855 TI - Value for money? PMID- 2109856 TI - Nursing without nurses. PMID- 2109857 TI - Non-androgenic role of testis in enhancing ventral prostate growth in rats. AB - This study was conducted to investigate whether the testis, aside from its ability to secrete androgen, is able to promote prostatic growth in rats. Increasing quantities of silastic capsules filled with crystalline dihydrotestosterone (DHT) were implanted subcutaneously into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham operation on the testes. Control animals received empty capsules. Twenty-eight days later, the growth of the ventral prostate as measured by wet weight, DNA, and protein content per prostate was significantly greater in rats with intact testes than in orchiectomized rats. An overall increased growth was noted at all doses of exogenous DHT administered. Serum levels of luteinizing hormone in animals treated with DHT were undetectable. Serum levels of testosterone in intact rats treated with DHT were not significantly different from those in castrated rats. These observations suggest a non-androgenic role for the testis and, perhaps, epididymis in promoting prostatic growth in rats, and are consistent with the concept that a non-androgenic substance, produced from the testis and/or epididymis, is able to enhance prostate growth induced by androgen stimulation. The possibility that this phenomenon may play a role in the benign growth of the prostate observed in aging human males with decreased blood levels of androgen warrants consideration. PMID- 2109858 TI - Role of cholinergic, vagal reflexes on the bronchoconstrictor responses to histamine during carbon dioxide inhalation in conscious guinea-pigs. AB - Histamine-induced bronchoconstriction in conscious guinea-pigs involves a cholinergic, bronchoconstrictor reflex, but the role of this reflex during elevated levels of inspired carbon dioxide is unknown. In this study we examined the role of cholinergic, vagal reflexes on the bronchoconstrictor responses to histamine during CO2 inhalation. Guinea-pigs were placed inside a whole body plethysmograph for measurement of tidal volume (VT), respiratory rate (f) and minute volume (V) and a head chamber was used to deliver a hypercapnic gas mixture (10% CO2, 21% O2, 69% N2) and for inhalation of aerosolized drugs. Inhalation of CO2 caused an increase in VT, f and V and these effects were reduced by exposure to aerosolized histamine (0.01-0.05% for 30 s). The histamine induced reduction of VT was significantly (P less than 0.05) attenuated following a 60 s exposure to inhaled atropine (0.03 and 0.1%) as was the reduction of VT due to inhaled methacholine. Intravenous atropine (1 mg/kg) also blocked the VT reduction due to aerosolized histamine. Intravenous administration of the ganglionic blockers hexamethonium (1 mg/kg) and mecamylamine (10 mg/kg) did not inhibit the histamine-induced reduction of VT at doses of these drugs that revealed systemic evidence of ganglionic blockade, i.e. inhibition of vagally stimulated bronchoconstriction and bradycardia. The results demonstrate that the bronchoconstrictor responses to histamine during CO2 inhalation in guinea-pigs involves stimulation of airway cholinergic receptors, but this response does not involve ganglionic neurotransmission. It is speculated that histamine's bronchoconstrictor effects during CO2 breathing involves stimulation of postganglionic, parasympathetic nerves innervating airway smooth muscle. PMID- 2109860 TI - Effect of praziquantel versus hycanthone on deoxyribonucleic acid content of hepatocytes in murine schistosomiasis mansoni. AB - Cytophotometric measurement of the effect of praziquantel (500 mg/kg for 2 days) versus hycanthone (60 mg/kg for 3 days) on hepatocyte nuclear deoxyribonucleic acid (DNA) content was evaluated in Schistosoma mansoni infected mice. Drugs were given 8 weeks post-infection and repeated weekly for 4 weeks. DNA values of infected untreated control and infected drug treated groups were related to the median and upper diploid DNA values of normal control. Schistosoma mansoni infection per se did not change the hepatocyte DNA content, yet aneuploidy was 16.7%. Praziquantel did not result in significant change of DNA content or ploidy, while hycanthone resulted in marked significant increase of DNA content (328.9%) and aneuploidy (100%), compared to infected untreated control. Histopathological examination revealed hyperchromatic nuclei with mitosis in the hepatocytes of hycanthone treated mice, but not in praziquantel treated animals. These DNA changes were found to correlate with the reported safety of praziquantel and the carcinogenicity of hycanthone. PMID- 2109859 TI - Antiarrhythmic effects of prostaglandins E2 and I2 on ouabain-induced cardiac arrhythmias in cats: effect of vagotomy and adrenergic neuron blockade. AB - The effects of i.v. prostaglandins (PGs) E2 and I2 on ouabain-induced cardiac arrhythmias were investigated in chloralose-anaesthetized cats. Bilateral vagotomy and guanethidine-pretreatment interventions were employed to elucidate the involvement of vagal and sympathetic neural influences in these effects. PGE2 (1 micrograms/kg/min i.v. infusion for 5 min) and PGI2 (4-16 microgram/kg i.v. bolus injections) effectively suppressed the ouabain-induced arrhythmias in a control group of cats. The bilateral vagotomy or guanethidine-pretreatment interventions did not significantly alter the antiarrhythmic effects of PGE2 and PGI2. It is concluded that the presence of functionally intact sympathetic and vagal nerve supply to the heart is not a prerequisite for the antiarrhythmic effects of i.v. administered PGE2 and PGI2. The possible role of direct action of these PGs on the myocardium is discussed. PMID- 2109861 TI - Inhibition of ornithine-decarboxylase produced by S(+) and R(-) ibuprofen in rats. AB - The differences between the S(+) and R(-) ibuprofen enantiomers in anti inflammatory activity were assayed by measuring the release of 14CO2 in rats treated with labelled 14COOH-ornithine. Furthermore we investigated in vitro the inhibitory activity on ornithine-decarboxylase and the anti-inflammatory activity of R(-) and S(+) ibuprofen by using the carrageenin-induced paw oedema test in the rat. PMID- 2109862 TI - [Histomorphology of the female breast in the human following long-term Testoviron therapy]. PMID- 2109863 TI - [The results of the intraportal allotransplantation of pancreatic islet cell cultures in patients with insulin-dependent diabetes mellitus]. AB - The paper is concerned with the results of the treatment of 11 patients with insulin-dependent diabetes mellitus with surgical pathology by a method of intraportal allotransplantation of pancreatic islet cell (PIC) cultures and with similar surgical pathology without PIC transplantation. Carbohydrate metabolism and the level of plasma hormones were investigated. It has been shown that intraportal administration of PIC suspension into the liver can result in an earlier and more considerable decrease in a dose of exogenous insulin that is very important in the postoperative period. This method permitted double reduction of diabetic patients' stay in hospital. PMID- 2109864 TI - [The nature of the pancreatic hormone secretion and of the metabolic indices during the acute and chronic administration of peroral hypoglycemic preparations]. AB - A comparative study of the effect of acute and chronic administration of sulfanilureal sugar lowering drugs (glipizide and glibenclamide) on the secretion of the pancreatic hormones, indices of microcirculation, the level of triglycerides and nonesterified fatty acids was conducted. Patients with primary detected diabetes mellitus with normal body mass and obesity of I-III degrees were investigated. The principal differences in insulinotropic action of sugar lowering drugs in various groups of patients and significant differences in the mechanism of their hypoglycemic action at varying time of treatment indicate the necessity of a strictly differentiated approach to subscription of these drugs for patients with primary detected diabetes mellitus. PMID- 2109865 TI - [The mechanisms of the decrease in prostatic mass in rats during the administration of estrogenic preparations into the cerebrospinal fluid]. AB - Experiments on albino male rats have shown that the endoliquor administration of estrogens at low doses results in the inhibition of proliferative processes in the prostatic tissues comparable with that observed at the administration of doses two orders larger, and at the subcutaneous administration. A study of the possible mechanism of the observed phenomenon has shown that this effect is associated with the fact that in such a way of estrogen administration conditions are created for deeper inhibition of the production of gonadotropins by the adenohypophysis, and as a result of it a decrease in the androgen level is observed leading to the inhibition of proliferative processes in the prostatic tissues. PMID- 2109866 TI - [Methods for assessing the somatotropic function in children]. PMID- 2109867 TI - Effects of arachidonic acid in the rabbit pulmonary and systemic vascular beds in vivo. AB - We studied the effects of arachidonic acid (AA) in the pulmonary and systemic circulations of rabbit under constant blood flow conditions in vivo, using a total heart bypass model. AA (100-150 micrograms/kg) injected into the pulmonary artery produced a dose-dependent increase in pulmonary arterial pressure (Ppa), without altering systemic arterial pressure (Psa). Conversely, injection of AA into the aorta reduced Psa in a dose-dependent fashion, but did not significantly alter Ppa. FPL55712, a leukotriene receptor antagonist, did not affect any of these responses to AA. Indomethacin, a cyclo-oxygenase inhibitor, totally prevented the pulmonary pressor response to intravenously administered AA and reduced the systemic depressor response to intra-arterially administered AA. The thromboxane A2 synthetase inhibitor, 7-(1-imidazolyl)heptanoic acid, totally abolished the increase in Ppa in response to intravenously administered AA, but did not alter the dose-dependent decrease in Psa in response to intra-arterially administered AA. These results suggest that in rabbits (1) AA produces pulmonary vasoconstriction and systemic vasodilation, (2) blood metabolites of AA mediate these effects and are then rapidly deactivated, and (3) AA-induced pulmonary vasoconstriction appears to be largely dependent on thromboxane A2. PMID- 2109868 TI - No evidence of interference of hypocapnia/respiratory alkalosis with classical conditioning of electrodermal responses. AB - Most phobias can be traced to aversive experiences relating to the phobic cue, but most aversive experiences do not result in phobias. Why is it that only sometimes these experiences result in classical conditioning of fear? It was hypothesized that if the subject is in a state of hypocapnia/respiratory alkalosis, classical conditioning of fear is facilitated, while extinction of fear responses is inhibited. Thirty-two healthy volunteers underwent a classical conditioning procedure with slides as conditioned stimulus, electric shocks as unconditioned stimulus, and electrodermal responding as (un) conditioned response. During conditioning, half of the subjects hyperventilated and were hypocapnic/alkalotic, while the other half was not. In both groups clear conditioning occurred, but there was no effect of hypocapnia. Results are critically discussed. PMID- 2109869 TI - Zonisamide-induced mania. PMID- 2109870 TI - [Effects of verapamil and disopyramide phosphate on the termination, reinduction and long-term prevention of paroxysmal supraventricular tachycardia]. AB - The efficacy of verapamil and disopyramide phosphate for the termination and prevention of paroxysmal supraventricular tachycardia (PSVT) were studied electrophysiologically in 32 patients with inducible sustained PSVT (17 patients received verapamil, 15 patients received disopyramide). Twelve patients had atrioventricular nodal tachycardia, 7 had concealed and 13 had overt Wolff Parkinson-White syndrome. Intravenous verapamil (0.15 mg/kg) terminated the sustained PSVT in 15 of the 17 patients (88%) by production of AV block in 13 patients, VA block in one, and a ventricular premature beat in one. PSVT could not be induced in any of these 15 patients after they had received verapamil. In the remaining 2 patients, PSVT could not be terminated by the use of verapamil, but the cycle lengths of PSVT were lengthened. Long-term oral dosages of verapamil of 120-240 mg/day were administered in 13 of the 17 patients. All patients except two, whose PSVT was unable to be effected by intravenous verapamil, were well controlled: PSVT disappeared in 7 patients and decreased in 4. Intravenous disopyramide (1.5 mg/kg) terminated induced PSVT in 10 of the 15 patients (67%) by production of VA block. Although PSVT could not be reinitiated in 5 of these 10 patients, non-sustained PSVT was induced in 2 and sustained PSVT was induced in 3 after having received disopyramide. PSVT was induced in all of the 5 patients who failed to respond to disopyramide. The cycle lengths of PSVT after administration of disopyramide remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109871 TI - Eaton agent--science and scientific acceptance: a historical commentary. AB - The three classical papers published in 1944 and 1945 by Monroe A. Eaton and colleagues deal with the etiology of primary atypical pneumonia (PAP) and with the properties of a filterable agent (subsequently and for a number of years known as Eaton agent) from the sputum or lung of patients with PAP using cotton rats, hamsters, and chick embryos as laboratory hosts. The present review is first and foremost a tribute to Monroe Eaton and his colleagues for their trail blazing discovery of a major cause of the atypical pneumonia syndrome and their steadfast vision of its importance. The organism was finally identified and designated Mycoplasma pneumoniae some 20 years after their papers first appeared in the Journal of Experimental Medicine. PMID- 2109872 TI - Interferon-gamma associated with conventional therapy for recurrent visceral leishmaniasis in a patient with AIDS. PMID- 2109873 TI - Interactions of cyclosporine with antimicrobial agents. PMID- 2109874 TI - Malaria vaccines. PMID- 2109875 TI - Comparative in vitro activity of several antimicrobial agents against selected clinical isolates. AB - A comparison between the in vitro activities of ceftazidime, cefotaxime, ceftriaxone, ampicillin, piperacillin, gentamicin, tobramycin and netilmicin was performed on selected clinical isolates. The activity of the agents was assessed by means of minimum inhibitory concentration determinations, and time-kill studies. The third generation cephalosporins were active against all members of the Enterobacteriaceae excluding some Enterobacter species. Their activity against these bacteria was generally comparable and greater than that of piperacillin. Netilmicin was the most active of the aminoglycosides tested against members of the Enterobacteriaceae; however, aminoglycoside-resistant strains were encountered. Ceftazidime was the most active of the third generation cephalosporins against the non-fermenters (e.g. Pseudomonas and Acinetobacter spp), its inhibitory activity also being greater than that of piperacillin. Using a time-kill study, ceftazidime also demonstrated greater bactericidal activity than piperacillin against an isolate of Pseudomonas aeruginosa. The aminoglycoside demonstrating the greatest activity against the non-fermenters was tobramycin. PMID- 2109876 TI - Alterations of IgE immunoglobulin concentration in the serum after megavoltage radiotherapy with large-field technique in patients with Hodgkin's disease. AB - In patients with Hodgkin's disease, the serum IgE concentrations were determined with the PRIST radioimmunoassay before commencing and after ending systemic megavoltage radiotherapy. 57 patients showed mainly raised serum IgE concentrations before radiotherapy. After the end of radiotherapy, 44 patients were investigated, and a highly significant fall of the IgE concentration was shown in the serum following the radiotherapy. The decrease of IgE concentration was most pronounced in the patients in whom large areas of irradiation were necessary or who displayed B symptoms. In a proportion of the patients, the IgE concentration in the serum could be measured once more six and twelve months after the end of radiotherapy. Although the IgE concentrations rose again after radiotherapy, the initial values before the beginning of radiotherapy had not yet been reached again even twelve months after treatment in 21 patients investigated. A long-lasting immunosuppressant effect of radiotherapy on the serum IgE concentration could thus be demonstrated which corresponds to the effect on the serum IgM concentration described earlier. PMID- 2109877 TI - [The use of absorbers to optimize the surface dosage in treatment using ultrahard x-rays]. AB - The surface dose in megavoltage x-ray therapy can be modified using two different techniques: either varying the thickness of an absorber positioned directly on the surface of the patient or varying the distance to the surface of an absorber with constant thickness. Surface dose as a function of distance and absorber thickness has been measured at 4 MV and 8 MV x-rays. Both methods yield sufficiently and well-defined dose enhancements at the surface of the patient as desired clinically. The variation of the absorber-surface distance however has been proved to be the more simple and practicable method, offering the additional advantage of no contacting the patients skin. PMID- 2109879 TI - [No way out of working?. Interview by Kjell Arne Bakke]. PMID- 2109878 TI - [Water-energy dosage calibration and standard ion dosage calibration--a comparison in ultrahard x-ray radiation]. AB - Ten ionization chambers (PTW), partly of different type, which all have been calibrated in terms of absorbed dose to water, were used to compare the absorbed dose indicated in a reference geometry at 8 MV X-rays. The standard deviation of the mean value of the absorbed dose determined for all chambers was 0.5%. Since 4 chambers have been calibrated in terms of absorbed dose to water and in exposure, the absorbed dose to water was determined from indicated value according to both calibration procedures. The dose values obtained via the energy dose calibration turned out to be about 2.5% less compared to the result when applying the exposure calibration factor. PMID- 2109880 TI - [Form a circle around the welfare state!]. PMID- 2109881 TI - [Congratulations with the little one--but was everything OK on the ward?]. PMID- 2109883 TI - [Patients' rights are most important. Interview by Siv Barstad Heide]. PMID- 2109882 TI - [Clearly, we shall be even better!]. PMID- 2109884 TI - [Complaints about salary. Interview by Kjell Arne Bakke]. PMID- 2109885 TI - [Together against cutbacks]. PMID- 2109886 TI - [Health visitor services at ease]. PMID- 2109887 TI - [Ventures barely seen to progress]. PMID- 2109888 TI - [Community venture at health center. Interview by Bjorn Arild Ostby]. PMID- 2109889 TI - [Oslo community: a new kind of popular movement]. PMID- 2109890 TI - [Oslo community: irresponsible to be responsible]. PMID- 2109891 TI - [Oslo hospitals in a time of transition]. PMID- 2109892 TI - [Psychiatry + somatic medicine = SANT]. PMID- 2109893 TI - [We have gotten a new extension. Interview by Bjorn Arild Ostby]. PMID- 2109894 TI - [Get faculty for nursing college]. PMID- 2109895 TI - [Air ambulance services--a dangerous place of work?]. PMID- 2109896 TI - [Greetings from a political prisoner]. PMID- 2109898 TI - [Oslo community: the assigned concerning their new job. Interview by Kjell Arne Bakke]. PMID- 2109897 TI - [Showcase of the Norwegian Nurses' Association!. Interview by Kjell Arne Bakke]. PMID- 2109899 TI - [Oslo community: replacements in grand style. Interview by Kjell Arne Bakke]. PMID- 2109900 TI - Nutritional state of patients with lung cancer undergoing thoracotomy. AB - Preoperative nutritional assessment was carried out on 39 consecutive patients with bronchial carcinoma who underwent thoracotomy. For 18 patients the body mass index and triceps and subscapular skinfold thickness fell below the 25th centile. In 23 patients the creatinine height index was less than 80% of the predicted value. The mean (SEM) serum albumin concentration was 40.3 (0.57) g/l (reference range 35-50 g/l) and mean (SEM) serum transferrin 1.77 (0.1) g/l (reference range 2.0-3.0 g/l). Although only three patients were hypoalbuminaemic, transferrin concentrations were depressed in 26 patients. There was a significant fall in the serum concentrations of both prealbumin and transferrin in the first postoperative week. Nutritional insufficiency was particularly severe in the four patients who developed an early bronchopleural fistula. It is concluded that protein-energy malnutrition is common in patients with operable bronchial carcinoma and that routine postoperative feeding does not prevent further depletion of circulating proteins. A larger prospective study is needed to examine the relation between preoperative nutritional state and outcome. PMID- 2109901 TI - Long term domiciliary oxygen treatment for chronic respiratory failure reviewed. AB - The use of long term domiciliary oxygen therapy in the Sheffield area from June to August 1987 has been surveyed. Of the 74 patients prescribed long term domiciliary oxygen therapy, 64 were visited at home. These had arterial blood gas tensions or oxygen saturation measured (while breathing oxygen and air), and the indications for long term domiciliary oxygen therapy were examined retrospectively. Fifty two patients had chronic bronchitis and emphysema, the remainder having pneumoconiosis, bronchiectasis, fibrosing alveolitis, and congestive cardiac failure. Of the 54 cases where indications for treatment could be compared with the Department of Health and Social Security (DHSS) guidelines, only 23 (43%) met the full DHSS criteria before the start of treatment. The median length of treatment was 16 months. At follow up 51 patients had an arterial oxygen tension (PaO2) greater than 8.0 kPa when breathing oxygen. They had a significantly higher PaO2 when breathing air than before long term oxygen therapy (6.7 (SD 1.2) kPa before oxygen treatment, 7.6 (1.4) kPa on reassessment). A similar change was seen in the 23 patients assessed as recommended by the DHSS (6.1 (0.8) kPa; 7.2 (1.2]. PaO2 during the breathing of air was less than 7.3 kPa at reassessment in only 21 (33%) patients. Thirteen patients had carboxyhaemoglobin concentrations above 2.5%, the 95th centile of the distribution in nonsmokers in the laboratory. PMID- 2109902 TI - Increase in colony stimulating factor (CSF) in serum and augmentation of CSF responsiveness of lymphoid mononuclear cells by acute Trypanosoma cruzi infection in mice. AB - Acute infection of Trypanosoma (T.) cruzi to C3H/HeN mice caused the induction of a higher level of serum colony stimulating factor (CSF) activity to support the proliferation of mouse bone marrow cells. The CSF activity reached a maximum 2 days after the infection and declined thereafter. Spleen cells of the T. cruzi infected mice showed higher levels of responsiveness to CSF in L929-conditioned medium, mouse recombinant GM-CSF and infected mouse sera as compared with normal mouse spleen cells. The induction of CSF-responding cells became plateau 4 days after the infection and it decreased thereafter. In concomitant with the production of CSF activity in the infected mouse sera, large granular cells bearing high intensity of Mac-2 antigen increased in the infected mouse spleen. These cells were nylon nonadherent and displayed inhibitory effect on T cell response to Con A. These findings indicate that T. cruzi infection induces augmentation of in vivo CSF production, leading to the abnormal proliferation of CSF-responding cells and that augmented production of, and responsiveness to, CSF might be one of important mechanisms responsible for the induction of immune abnormalities in T. cruzi-infected mice. PMID- 2109903 TI - High dose intact-immunoglobulin treatment for an HIV-infected asymptomatic carrier with hemophilia. AB - Intravenous administration of a high dose of intact-immunoglobulin to a human immunodeficiency virus (HIV) infected patient with hemophilia A, whose total lymphocyte and CD4 positive lymphocyte counts showed a decreasing tendency, resulted in a gradual rise in these cell counts. The results were quite reproducible on another occasions. Therefore, intravenous administration of gammaglobulin (IVGG) was thought to be effective for preventing further deterioration of cellular immunity and progression from asymptomatic carrier (AC) to AIDS related complex (ARC)/AIDS in hemophilia patients. PMID- 2109904 TI - Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide induced limb malformations. AB - The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5' dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL/6) and resistant (SWV) inbred mice. pHi was reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+/H+ exchange attributable to the latter agent. pHi reduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development. PMID- 2109905 TI - Clinical and reproductive effects of Clophen A50 (PCB) administered during gestation on pregnant guinea pigs and their offspring. AB - Female and male guinea pigs exposed to polychlorinated biphenyls (PCBs) in utero and via mother's milk showed growth retardation and signs of delayed onset of sexual maturation. In female young exposed to PCBs first vaginal opening occurred at a significantly older age and was of shorter duration compared with control females. The age at the first ovulation did not differ significantly between PCB exposed females and control females. Male young exposed to PCBs had significantly lower absolute and relative testis weights at 3 months of age compared with control males. No differences in plasma testosterone concentrations were observed. PMID- 2109906 TI - Inhibitory effects of beryllium chloride on rat liver microsomal enzymes. AB - A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P 450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine. PMID- 2109907 TI - Effects of chemical modifications of Pa-11, a phospholipase A2 from the venom of Australian king brown snake (Pseudechis australis), on its biological activities. AB - Pa-11, a phospholipase A2 isolated from the venom of an Australian elapid snake Pseudechis australis, was chemically modified and its enzymic, neuromuscular and lethal activities were studied. Carboxymethylation of Met-8 gave a derivative with 2% of the enzymic activity and less than 3% of the lethal activity of native Pa-11; it had about 5% of the original ability to block directly and indirectly stimulated mouse phrenic nerve-hemidiaphragm preparations. Nitrophenylsulfenylation of tryptophanyl residues at positions 31 and 69 caused loss of all activities. Amidination of all 14 lysyl residues gave a derivative with 41% and 16% of the enzymic and lethal activities, respectively, but with less than 5% of the original neuromuscular blocking activity. Mono-carbamoylation of lysyl residues at positions 58, 63, 81 and 85 was achieved. The most abundant derivative, 58-carbamoyl-lysine Pa-11 was enzymically 130% and lethally 100% as active as native Pa-11, but it had only about 20% of the native's neuromuscular activity in vitro. 63-Carbamoyl-lysine Pa-11 had 10% of the enzymic and 20% of the lethal activities, respectively; however, it retained at least 50% of its ability to block neuromuscular transmission in vitro, while losing most of its activity to block directly stimulated muscle contractions. 81- and 85-Carbamoyl derivatives have the same enzymic and lethal activities as the original protein, but the 85 derivative had less than 10% of the native neuromuscular activity. Hence, modifications of lysine residues at positions 58, 63 and 85 seem to be particularly significant in altering the neuromuscular, but not enzymic, activity of Pa-11, perhaps by altering the ability of the toxin to bind to its target on nerve and muscle membranes. Modification at position 63 appeared to lead to a dissociation of effects on neuromuscular transmission and directly on muscle cells. PMID- 2109908 TI - Isolation and characterization of the minor components associated with microcystins LR and RR in the cyanobacterium (blue-green algae). AB - Two structurally similar analogues of microcystins LR and RR, cyclic peptide hepatotoxins from Microcystis, were isolated by chromatographic methods. Although they have the same mol. wt and amino acid compositions as those of the parent toxins, they do not possess similar toxicities. Ultraviolet and 1H-NMR spectral data for both components demonstrate clear structural difference of these cyclic peptides from the parent toxins, which are probably responsible for the marked decreases in their observed toxicities. PMID- 2109909 TI - Isolation of a galactose-binding lectin from the venom of the snake Bothrops godmani (Godmann's pit viper). AB - A galactose-binding lectin, isolated from the venom of B. godmani by affinity chromatography, is an acidic protein (pI 4.9) with a subunit mol. wt of about 14,000, occurring mostly as a disulfide-linked dimer of 28,000. A small proportion of lectin appears as a monomer and as a tetramer. The lectin agglutinates erythrocytes from mice, rabbit, cow and human (all ABO types, either Rh positive or negative), but does not agglutinate horse, sheep, goat and snake (Oxybelis aeneus, Colubridae) erythrocytes. The agglutinating activity is inhibited by 1 mM EDTA. The lectin is devoid of lethal, hemorrhagic, myotoxic, proteolytic and phospholipase A2 activities. It is not mitogenic for human peripheral blood mononuclear cells. The only effect observed was a moderate induction of edema in the footpad of mice, with a minimal edema-forming dose of 22 micrograms. This effect developed rapidly, and was significantly inhibited by i.p. administration of cyproheptadine, a histamine and serotonin antagonist, before injection of the lectin. Despite the edema-forming activity observed, the low concentration of lectin in crude venom, together with its relatively low potency, suggest that this lectin is not a key component in the development of edema following envenomations by B. godmani. PMID- 2109910 TI - Investigations on benzyltoluenes. I. Induction of microsomal cytochrome P-450 and UDP-glucuronosyltransferase by tetrachlorobenzyltoluenes and by the condensate. AB - Tetrachlorobenzyltoluene (TCBT) (Ugilec 141) was investigated in induction experiments in male and female Wistar rats with long-term (50, 100 and 300 mg/kg p.o. daily for 28 days) and short-term administration (300 mg/kg once and 100 mg/kg daily for 4 days). The increase in total cytochrome P-450 did not exceed the factor of 1.9 compared to controls, while benzphetamine N-demethylase rose up to 3.5-fold the levels measured in controls, with very low induction of benzo(a)pyrene hydroxylase or ethoxyresorufin O-deethylase. Parallel investigations of UDP-glucuronosyltransferase showed induction of testosterone glucuronidation (1.7-fold). Administration (300 mg/kg body wt. once) of a pyrolysate of TCBT resulted in a marked increase in cytochrome P-450c dependent reactions (benzo(a)pyrene hydroxylase, ethoxyresorufin O-deethylase). PMID- 2109911 TI - Combination therapy for penile giant Buschke-Lowenstein condyloma. AB - The case of a 25-year-old patient who underwent circumcision and Neodymium-YAG laser treatment for giant condylomata acuminata of the penis is presented. Two cycles of interferon therapy were administered postoperatively, each comprising beta-interferons and recombinant gamma-interferons. This combination therapy provided an excellent cosmetic and functional result and the patient remains disease-free 15 months following surgery. PMID- 2109912 TI - Functional domains of the HIV-1 rev gene required for trans-regulation and subcellular localization. AB - The rev gene of human immunodeficiency virus type 1 (HIV-1) encodes a 116 amino acid nuclear regulatory protein (Rev) that increases the cytoplasmic expression of viral mRNAs containing the Rev response element (RRE) and coding for the structural proteins, Gag and Env. To identify the functional domains of Rev, amino acid deletion and chain termination mutations were introduced in the Rev coding region. The ability of these mutants to increase the cytoplasmic expression of a Rev-test plasmid (pSV-AR), containing the RRE cloned into the 3' noncoding region of the CAT gene in plasmid pSV2CAT, was examined in transient expression assays in HeLa cells. Our results indicate that three distinct regions mapping within the N-terminal 98 amino acids of Rev are essential for its activity. The subcellular localization of the various Rev proteins was examined in COS cells by indirect immunofluorescence. Rev was found to localize predominantly in the nucleolus of transfected cells. All mutant Rev proteins, with the exception of a deletion mutant (rev delta 41-44) lacking four Arg residues of a highly basic domain, were found to localize in the nucleolus. Mutant rev delta 41-44 exhibited weak diffuse fluorescence in the nucleus with a tendency to accumulate in the cytoplasm. A 15 amino acid region encompassing this basic domain (38-52) when fused to the Escherichia coli beta-galactosidase gene efficiently directed the fusion gene product to the nucleus and nucleolus, suggesting a role for this domain in the nucleolar localization of Rev. PMID- 2109913 TI - [Antitumor effectiveness and nephrotoxicity of oxoplatinum]. AB - Studies on such transplantable murine tumors as MOPC-21 plasmacytoma and Krebs-2 carcinoma showed oxoplatinum course administration to produce necrosis in solid tumors and pronounced alterations in surviving tumor cells. Single applications of 15 or 20 mg/kg were followed by an increase in the mean survival of Krebs-2 ascites carcinoma--bearing mice by one half. Oxoplatinum--induced changes in the renal tissue ranged from moderate under continuous administration to acute renal failure after high--dose treatment. Such diuretics as diacarb, furosemide and, particularly, mannitol did not interfere with oxoplatinum activity against solid and ascites tumors but assured less pronounced structural disorders in the kidney as compared to oxoplatinum alone. PMID- 2109914 TI - [The effect of thyroliberin on the blood level of gonadotropins and sex steroids in women suffering from Itsenko-Cushing disease]. AB - The authors examined the level of gonadotropin (lutropin, follitropin) and sex steroids (estradiol, progesteron, testosterone) before and after administration of thyroliberin in 10 healthy women and 15 females suffering of Itsenko-Cushing disease. It was established that both the healthy and patients with Itsenko Cushing disease did not reveal any significant changes in the level of lutropin, follitropin, estradiol, progesteron, testosteron after administration of thyroliberin within 2 hours of the examination. Data indicate absence of paradoxic response of gonadotropins and cells secreting sex steroids in Itsenko Cushing disease. PMID- 2109915 TI - [An analysis of the mechanisms of interpopulation interaction of Yersinia with Tetrahymena pyriformis infusorians at the cellular and subcellular levels]. AB - The mechanisms of interaction between the populations of Yersinia and T. pyriformis have been analyzed on the cellular and subcellular levels. As shown in this investigation, Yersinia, when phagocytized by T. pyriformis, may undergo morphological changes, remain unchanged and also multiply, destroying the host cell in the process. PMID- 2109917 TI - The value of fat reserves and the tradeoff between starvation and predation. AB - It is shown that in a range of models, the probability that a forager dies from starvation is, to a good approximation, an exponential function of energy reserves. Using a time and energy budget for a 19g passerine, we explore the consequences, in terms of starvation and predation, of various levels of energy reserves. It is shown that there exists an optimal level L* of reserves at which total mortality (starvation plus predation) is minimized. L* increases when the environment deteriorates as a result of a decrease in either temperature or mean gross gain or an increase in the mean search time. The effect of combined deteriorations is greater than the sum of their individual effects. At L*, the probability of predation is much higher than the probability of starvation. A simple analytic model suggests that this result will be fairly general, but also indicates conditions under which the result might not hold. PMID- 2109916 TI - Catastrophe modelling in the biological sciences. AB - Catastrophe Theory was developed in an attempt to provide a form of Mathematics particularly apt for applications in the biological sciences. It was claimed that while it could be applied in the more conventional "physical" way, it could also be applied in a new "metaphysical" way, derived from the Structuralism of Saussure in Linguistics and Levi-Strauss in Anthropology. Since those early beginnings there have been many attempts to apply Catastrophe Theory to Biology, but these hopes cannot be said to have been fully realised. This paper will document and classify the work that has been done. It will be argued that, like other applied Mathematics, applied Catastrophe Theory works best where the underlying laws are securely known and precisely quantified, requiring those same guarantees as does any other branch of Mathematics when it confronts a real-life situation. PMID- 2109918 TI - A possible model for the genetics of certain diseases. PMID- 2109919 TI - Properties of urokinase type-plasminogen activator found in chest fluid. AB - Urokinase type plasminogen activator (u-PA) was purified from three different chest fluids obtained from patients with liver cirrhosis and pleuritis, aplastic anemia and pneumonia, and lung tumor, and the relationship between molecular weight and plasminogen activator (PA) activity was examined by zymography. The molecular weights of u-PAs from the chest fluids were 200 Kd, 150-180 Kd, 95 Kd, 55 Kd, 44 Kd, 33 Kd and 14 Kd, and PA activity was observed at molecular weights of 95 Kd, 55 Kd and 33 Kd. Fibrin binding of u-PA was observed at molecular weights of 55 Kd and 33 Kd. PMID- 2109920 TI - Haematopoietic suppressing activity of gamma-interferon in serum and bone marrow of aplastic anaemia patients. AB - To determine the mechanism by which haematopoiesis is suppressed in aplastic anaemia, the effect of the sera from 6 patients on the granulopoietic precursors (colony-forming units in culture; CFU-C) was studied in vitro. Addition of the sera from 2 patients significantly suppressed CFU-C. The suppressive effect of the sera on CFU-C was inhibited by the addition of 1.5 NU/ml of anti-gamma-IFN antibody. In another patient, anti-gamma-IFN antibody increased autologous CFU-C although the serum of the patient did not suppress CFU-C. Serum gamma-IFN levels of all patients were under 2 IU/ml. The above findings suggest that humoral factors inhibit haematopoiesis in some patients with aplastic anaemia, and that gamma-IFN plays a role as an inhibitor even at a low concentration. PMID- 2109921 TI - Gamma interferon production and two-color fluorescence flow cytometry analysis of peripheral blood mononuclear cells in allogeneic bone marrow transplant recipients. AB - Gamma interferon (gamma-INF) production was studied and two-color fluorescence flow cytometry analysis was done on the peripheral blood mononuclear cells (PBMC) in allogeneic bone marrow transplant recipients. Gamma INF was not detected in any patients within a year after transplantation whether PBMC was stimulated with PHA or not. A year after transplantation, gamma-INF was produced in the normal level in the stimulated and unstimulated PBMC. The number of suppressor-inducer T cells (CD4+2H4+) was decreased and that of suppressor T cells (CD11+CD8+) was normal. The numbers of helper-inducer T cells (CD4+4B4+) and helper T cells (CD4+2H4-) were normal. The numbers of activated helper-inducer T cells (CD4+HLA DR+) and suppressor-cytotoxic T cells (CD8+HLA-DR+) were elevated. In the NK cells, Leu7+ CD16-cells were elevated, whereas Leu7+CD16+ cells and Leu7-CD16+ cells were normal. Leu7+CD8+ cells were elevated. These results indicated immunodeficiency after transplantation. PMID- 2109922 TI - The Ramsay Hunt syndrome revisited: Mediterranean myoclonus versus mitochondrial encephalomyopathy with ragged-red fibers and Baltic myoclonus. AB - Among progressive myoclonus epilepsies (PME), the nosography of the Ramsay Hunt syndrome (RHS) has been much debated. The authors report on a homogeneous group of 43 patients originating from around the western Mediterranean, with a large number of northern African subjects, who were followed up for a mean period of 11.6 years. Onset is between 6 and 17 years (mean: 11.2) and the transmission appears to be recessive. The clinical features include: action myoclonus, generalized epileptic seizures, mild cerebellar signs and lack of dementia. EEG features include normal background activity, spontaneous fast generalized spike wave discharges, photosensitivity, lack of activation during nREM sleep and vertex/rolandic spikes during REM sleep. The prognosis is variable, even within families, but the progression seems to be slow in a majority of patients. This condition can be distinguished from mitochondrial encephalomyopathy and is less severe than Baltic myoclonus. The authors propose that this form of PME, formerly reported as RHS, be more properly described as Mediterranean myoclonus. PMID- 2109923 TI - Lupus anticoagulant and late onset seizures. PMID- 2109924 TI - Effects of glyburide on ischemia-induced changes in extracellular potassium and local myocardial activation: a potential new approach to the management of ischemia-induced malignant ventricular arrhythmias. AB - The increase in extracellular potassium [K+]o levels during the early phase of myocardial ischemia may result in part from activation of adenosine triphosphate sensitive K+ channels. Glyburide, a second-generation hypoglycemic sulfonylurea, is a potent blocker of these channels. We studied the effects of glyburide on [K+]o and on intramyocardial conduction delay during a 10-minute occlusion of the left anterior descending artery in the dog. K(+)-sensitive electrodes and bipolar plunge electrodes were introduced to record, respectively, [K+]o and local electrograms from close sites in midmyocardial regions in normal, border, and ischemic zones. Recordings were obtained before (control ischemia [CI]) and 20 minutes after intravenous administration of 0.15 mg/kg of glyburide (glyburide plus ischemia [G + I]). During G + I the extent of the increase in [K+]o was less compared to that during CI, and the difference was statistically significant during the first 7 minutes of ischemia in the ischemic zone and during the first 4 minutes of ischemia in the border zone. On the other hand, the degree of local intramyocardial conduction delay was significantly reduced during G + I compared to CI during the entire 10 minutes of ischemia in both the ischemic and border zones. In summary, our results have shown that glyburide significantly reduced the rise of [K+]o and intramyocardial delay during the early phase of acute ischemia and could thus attenuate the electrophysiologic consequences of ischemia that underlie the initial phase of malignant tachyarrhythmias. Although the effects of glyburide may result in part from a direct action of the drug on cardiac adenosine triphosphate-sensitive K+ channels, other metabolic antiischemic effects cannot be ruled out. PMID- 2109925 TI - Arterial baroreceptor control of peripheral vascular resistance in experimental heart failure. AB - Heart failure is known to impair arterial baroreceptor control of heart rate. To determine if baroreceptor control of peripheral vascular resistance is also impaired, heart rate and hind limb vascular responses to phenylephrine and nitroglycerin administration were compared in control dogs and in dogs with heart failure produced by chronic rapid ventricular pacing. Baroreflex control of the heart rate was depressed in the dogs with heart failure, as evidenced by a reduced slope of the blood pressure-to-heart rate relationship (controls: -2.5 +/ 0.3 beats/mm Hg versus heart failure: -1.5 +/- 0.2 beats/mm Hg [(p less than 0.04)]). Arterial blood pressure in the dogs with heart failure was also reduced (controls: 90 +/- 3 mm Hg versus heart failure: 75 +/- 3 mm Hg [(p less than 0.01)]). Nevertheless, dogs with heart failure exhibited normal slopes of the blood pressure versus hind limb vascular resistance relationship (controls: -2.4 +/- 0.4 units/mm Hg versus heart failure: -2.9 +/- 0.5 units/mm Hg [(p = NS)]), consistent with preserved baroreflex control of the peripheral vasculature. These data suggest that heart failure impairs arterial baroreflex control of heart rate and lowers the baroreflex pressure operating range but does not alter baroreflex control of peripheral resistance. PMID- 2109927 TI - Hemodynamic, platelet and clinical responses to prostacyclin in unstable angina pectoris. AB - The hemodynamic and platelet effects of prostacyclin (PGI2) were investigated in 27 patients with unstable angina (14 treated patients; 13 control subjects) given a 72-hour infusion (5 ng/kg/min) or placebo. This randomized study was double blind and conducted as a substudy of a multicenter trial testing the clinical efficacy of PGI2. The clinical and angiographic features were identical in the 2 groups. Blood pressure and heart rate were not modified significantly by PGI2. A recurrence of angina during infusion occurred in 8 treated patients (57.1%) and in 8 control subjects (61.5%). Two patients receiving PGI2 and none in the control group developed a myocardial infarction. Levels of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2, increased from baseline values (less than 20 pg/ml) to 605 +/- 41 pg/ml during infusion. Levels of fibrinopeptide A, beta thromboglobulin, platelet factor 4, thromboxane B2 and the platelet aggregates ratio in blood were similar between the 2 groups before, during and after PGI2 infusion. Prostacyclin reduced ex vivo platelet aggregation to adenosine diphosphate and thromboxane B2 generation by approximately 50% during the infusion period with return of aggregation to baseline and platelet thromboxane B2 production to above baseline after the discontinuation of PGI2. Thus, despite favorable effects of PGI2 upon platelet aggregation and systemic hemodynamics, the prostanoid failed to improve the clinical evolution of unstable angina. PMID- 2109926 TI - Effectiveness of multiple bolus administration of tissue-type plasminogen activator in acute myocardial infarction. AB - The feasibility and possible advantages of intravenous bolus administration of recombinant tissue-type plasminogen activator (rt-PA) were investigated in 26 consecutive patients with early (less than 6 hours) evolving acute myocardial infarction. Either an intravenous infusion of 40 clot-lysis megaunits (cIMU) double-chain rt-PA over 1.5 hours followed by 20 cIMU over 5 hours (infusion group, n = 12) or 4 intravenous bolus injections of 10 cIMU at 20 minute intervals (bolus group, n = 14) were randomly administered. Coronary arteriography was performed before and at regular predefined intervals up to 90 minutes from the start of rt-PA administration, and at 24 hours. Acute recanalization of the infarct-related coronary artery was demonstrated in 7 of 12 patients (58%; 95% confidence interval 28 to 85%) in the infusion group and 11 of 14 patients (79%; 95% confidence interval 49 to 95%) in the bolus group (difference not significant). Two patients in the bolus group had reoccluded by 24 hours. Mean time from the start of rt-PA to patency of the infarct-related coronary artery was 39 +/- 6 (standard error of the mean) minutes in the infusion group and 28 +/- 6 minutes in the bolus group (p = 0.2). There were no significant differences in the minimum infarct-related coronary artery luminal diameter measured by computerized quantitative arteriography between the infusion group and the bolus group at 90 minutes or at 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109928 TI - Effects of indapamide on endothelium-dependent relaxations in isolated canine femoral arteries. AB - Indapamide is an effective antihypertensive agent in humans and in experimental hypertensive animals. The aim of the present study was to investigate whether indapamide affects endothelium-dependent and independent relaxations in canine femoral arteries. Rings (with or without endothelium) were contracted with prostaglandin F2 alpha (2 X 10(-6) mol/liter) before the addition, in a cumulative fashion, of relaxing agents. Indapamide (10(-7) to 10(-4) mol/liter) had no direct effect on unstimulated or prostaglandin-stimulated preparations; it did not alter relaxations of preparations with endothelium induced by acetylcholine, bradykinin, adenosine diphosphate or the calcium ionophore A23187. Similarly, it did not affect relaxations induced by sodium nitroprusside, prostacyclin or forskolin in preparations with or without endothelium. Indomethacin shifted the concentration-response curve to bradykinin to the right and did not alter that to the other relaxing drugs. The reduced relaxation to bradykinin was reversed in a concentration-dependent manner by indapamide (10(-7) to 10(-5) mol/liter). In the presence of indomethacin, indapamide shifted the concentration response curve to prostacyclin (in rings with endothelium) and to forskolin (in rings with and without endothelium) to the left. Thus, indapamide does not directly affect endothelium-dependent and independent relaxations. However, when prostanoid production is impaired, indapamide facilitates the release of endothelium-derived relaxing factor(s), and to a lesser extent, the direct action on vascular smooth muscle of prostanoids (prostacyclin) released from the endothelium. PMID- 2109929 TI - Gonococcal conjunctivitis in prepubertal children. AB - Four prepubertal children had confirmed gonococcal conjunctivitis. All were febrile and had hyperpurulent conjunctival discharge with periorbital inflammation. Cultures of pharyngeal, rectal, and genital specimens on selective media excluded infection at other sites. Detailed social evaluation revealed no evidence or suspicion of sexual abuse. Isolated gonococcal conjunctivitis occurs in prepubertal children. Unlike gonococcal infections at other locations, a nonsexual mode of transmission may exist. However, a careful physical examination and detailed social evaluation, looking for signs of sexual abuse, must be obtained in any prepubertal child with a gonococcal infection. PMID- 2109930 TI - Intracameral tissue plasminogen activator for treatment of excessive fibrin response after penetrating keratoplasty. PMID- 2109931 TI - K+ alters cytochrome P-450-dependent arachidonate metabolism by rabbit renomedullary cells. AB - We studied the effects of K+ on cytochrome P-450-dependent arachidonic acid (P450 AA) metabolism by cells isolated from the rabbit medullary thick ascending limb of Henle's loop (MTAL) by varying K+ from 0 to 7.5 mM in the incubating medium because of the known effects of K+ on AA metabolism. Rabbit MTAL cells convert AA to metabolites that segregate into two peaks (P1 and P2) on reverse-phase high performance liquid chromatography; P1 contains vasodilator material and P2 an inhibitor(s) of Na(+)-K(+)-ATPase activity. Formation of P450-AA metabolites by MTAL was enhanced by reducing external K+ (P less than 0.01) and was not affected by changes in external Cl- but was dependent on the presence of intact MTAL cells, suggesting that P450-AA metabolism was related to altering ion fluxes and/or cell volume changes. The effects of altered external K+ on MTAL P450-AA metabolism could be nullified by increasing K+ intake before killing the rabbits. Evidence for the absence of a direct effect of zero K+ on Na(+)-K(+)-ATPase was provided by the demonstration that ouabain failed to affect AA metabolism in MTAL cells. We conclude that P450-AA metabolism by MTAL cells can be influenced either directly by altering external K+ in the incubate or indirectly by changing dietary K+ before killing the rabbits. Furthermore, MTAL P450-AA metabolism was independent of changes in external Cl- and Na(+)-K(+)-ATPase activity. PMID- 2109932 TI - A micropuncture study of proximal tubular transport of lithium during osmotic diuresis. AB - Lithium and sodium are normally reabsorbed in parallel with water by the renal proximal tubule whereby their tubular fluid-to-plasma concentration ratios (TF/P) remain close to unity throughout the proximal convoluted segment. During osmotic diuresis, the late proximal (TF/P)Na is known to decrease. The present experiments were undertaken to study whether the late proximal TF/P for Li decreases like that of Na during osmotic diuresis. Data were obtained in a control period (C) and in two successive periods during mannitol diuresis (P1, P2). Glomerular filtration rate decreased gradually during osmotic diuresis [1,147 +/- 32 (C) to 950 +/- 22 (P2) microliters.min-1.g kidney wt (KW)-1, P less than 0.01), whereas Li clearance (CLi) increased [377 +/- 21 (C) to 469 +/- 28 (P1, P less than 0.01) and 408 +/- 25 (P2, NS) microliters.min-1.gKW-1, respectively]. (TF/P)Na decreased from 0.98 +/- 0.02 (C) to 0.89 +/- 0.02 (P less than 0.01) and 0.90 +/- 0.04 (P less than 0.05) (P1 and P2, respectively). (TF/P)Li was close to, but significantly higher than, unity during control (1.09 +/- 0.02), but, in contrast to (TF/P)Na, it did not decrease significantly during osmotic diuresis. Delivery of water from the proximal straight segment, as estimated from CLi/CIn, increased in proportion to the delivery from the convoluted segment, as estimated from 1/(TF/P)In. It is concluded that the proximal net Li reabsorption follows more closely the net water reabsorption than the net Na reabsorption during osmotic diuresis. PMID- 2109933 TI - Cytochrome P-450 arachidonate metabolites in rat kidney: characterization and hemodynamic responses. AB - Rat kidney cortical and medullary microsomal fractions catalyzed cytochrome P-450 linked metabolism of arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs) (56 +/- 6% of total products in cortex and 10% in medulla) and 19- and 20 hydroxyeicosatetraenoic acids (19- and 20-OHAA) (36 +/- 4% in cortex and 90% in medulla). In addition, endogenous renal generation of EETs was established by negative ion-chemical ionization mass spectrometry. The total amount of EETs present in the rat kidney was approximately 1 microgram/g wet tissue. The responses to renal arterial administration of 20-OHAA and 5,6-EET were evaluated in anesthetized euvolemic rats. 20-OHAA resulted in ipsilateral dose-dependent natriuresis without affecting systemic or renal hemodynamics or glomerular filtration rate (GFR). Equimolar doses of 5,6-EET resulted in dose-dependent renal vasoconstriction and reduced GFR but were without effect on arterial pressure or sodium excretion. During cyclooxygenase inhibition, 5,6-EET caused renal vasodilatation and augmentation of GFR. These data establish the capacity of rat kidney to metabolize AA through cytochrome P-450-dependent oxygenases and demonstrate the endogenous formation of the resulting eicosanoids. Monooxygenase and epoxygenase products exert effects on renal blood flow, GFR, and urinary sodium excretion rate, suggesting their potential relevance in the regulation of renal function. PMID- 2109934 TI - Effects of amino acid isomers on canine renal hemodynamics. AB - The major objective of this study was to ascertain whether the renal hemodynamic response to amino acid infusion in dogs is stereospecific. To test this hypothesis, we examined the renal hemodynamic effects of two isomers (L and D) of an amino acid mixture of serine, alanine, and proline (SAP; 0.051 mmol.kg-1.min 1) in anesthetized dogs. Intravenous infusion of L-SAP (n = 6) significantly elevated renal blood flow (RBF) and glomerular filtration rate (GFR) by 33 +/- 3 and 30 +/- 5%, respectively, over 1 h. DL-SAP (n = 6) elevated RBF and GFR by only 14 +/- 3 and 13 +/- 3%, respectively. Yet D-SAP (n = 6) failed to elevate either RBF or GFR over 1 h. Intravenous mannitol (940 mos-mol/kg; osmotic control; n = 6) also failed to elevate renal hemodynamics. In six other dogs, intrarenal infusion of L-, but not D-, SAP marginally elevated RBF and GFR by 13 +/- 2 and 12 +/- 2%, respectively, over 1 h. Infusion of alpha-aminoisobutyric acid (0.051 mmol.kg-1.min-1; n = 6), an amino acid analogue that is cotransported with sodium but not metabolized by renal cells, elevated RBF and GFR by 22 +/- 5 and 18 +/- 6%, respectively, over 1 h. These data indicate that vascular infusion of L, but not D, isomers of amino acids elevate RBF and GFR. We therefore suggest the importance of amino acid stereospecificity in the renal vascular response to amino acid infusion in dogs. PMID- 2109935 TI - Effect of cellular acidosis on cell volume in S2 segments of renal proximal tubules. AB - The presence of pH-sensitive transport mechanisms in the basolateral membrane of proximal tubular cells suggests that cell volume and its regulation may be sensitive to changes in cell pH. We have measured the response of cell pH and cell volume to changes in the acid-base composition of solutions bathing isolated, lumen-collapsed, proximal S2 tubular segments taken from the rabbit kidney. Cell pH was determined by measurement of the fluorescence emission of 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Cell volume was calculated from measurements of tubular diameter. An increase in CO2 from 5 to 15% reduced cell pH 0.30 units and raised cell bicarbonate concentration ([HCO3]) 10 mM. Cell volume rose to 108.6% of control in 4 min. A decrease in bath [HCO3] from 25 to 5 mM reduced cell pH 0.41 units and cell [HCO3] by 15 mM. Cell volume gradually increased to 105.7% at 8 min. The rate of the regulatory volume decrease after cell swelling on exposure to a 160 mosM solution was determined in the presence of 5 and 15% CO2. The latter reduced the maximum fractional rate of recovery of volume from 0.18 to 0.11 min-1 but did not affect the extent of regulation. We conclude that acidosis causes cell swelling and reduces the rate of volume regulation in response to hypotonic media. PMID- 2109936 TI - Total CO2 transport in rat cortical collecting duct in chloride-depletion alkalosis. AB - Previous studies in chloride-depletion metabolic alkalosis (CDA) generated by intraperitoneal dialysis have suggested major alterations in chloride and bicarbonate transport beyond the distal convoluted tubule. To investigate the possible role of the cortical collecting duct (CCD) in the pathophysiology of CDA, isolated CCD segments were perfused in vitro from either control (CON) rats dialyzed against Ringer-bicarbonate or those made alkalotic by peritoneal dialysis with 0.15 M NaHCO3. Tubules from CDA animals secreted CO2 for greater than or equal to 3 h after dissection (-22.4 +/- 7.2 pmol.mm-1.min-1) compared with CON tubules that absorbed CO2 (18.3 +/- 4.2 pmol.mm-1.min-1). Replacement of luminal chloride with gluconate in the perfusate abolished net total CO2 (tCO2) secretion in tubules from CDA animals (from -21.5 +/- 4.5 to -2.7 +/- 2.3 pmol.mm 1.min-1) but did not alter net tCO2 absorption in tubules from CON animals. In contrast, removal of bath chloride increased net tCO2 secretion (-12.1 +/- 2.9 to -26.1 +/- 3.6 pmol.mm-1.min-1) in CDA tubules, whereas net tCO2 flux was altered from absorption to secretion in CON tubules (15.5 +/- 4.0 to -13.6 +/- 9.2 pmol.mm-1.min-1). These results demonstrate that 1) CDA generated in vivo within 45 min results in stable net tCO2 secretion in vitro up to 240 min in the CCD; 2) luminal chloride is necessary for tCO2 secretion; 3) the shift of net tCO2 flux from absorption to secretion in CON tubules in vitro was not sustained in contrast to CDA tubules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109937 TI - Heterogeneities in regional volumes of distribution and flows in rabbit heart. AB - The heterogeneity of volumes of distribution in the heart influences the rates of uptake and washout of substrates and metabolites; thus it is important to evaluate their variability in the normal heart. Several tracers were injected intravenously into anesthetized adult closed-chest rabbits, and time was allowed for equilibration in the heart. Tracer microspheres were injected into the left ventricular cavity at the apex for the measurement of regional flows, the chest was opened, another set of microspheres was injected, and the heart was frozen rapidly in situ with liquid nitrogen-cooled Freon-22. Each heart was divided into 72 pieces of less than 0.1 g weight, and the tracer content of each was determined by multichannel gamma-counting and the water content by desiccation. The regional myocardial flows were (closed chest) 0.62 +/- 0.16 ml.g-1.min-1 and (open chest) 0.63 +/- 0.37 ml.g-1.min-1. The volumes of distribution (ml/g) for the 432 pieces for six rabbits, given as mean +/- SD (% coefficient of variation), were as follows: for plasma, VP = 0.11 +/- 0.03 (26%); erythrocytes, VRBC = 0.041 +/- 0.015 (37%); vascular space, VV = 0.15 +/- 0.04 (26%); extracellular space, VECF = 0.33 +/- 0.05 (15%); interstitial space, VISF = 0.21 +/- 0.03 (15%); and water space, VW -0.79 +/- 0.022 (2.8%). Regional hematocrits were 77% +/- 9% of the large-vessel hematocrits. PMID- 2109938 TI - Endothelial modulation of norepinephrine-induced constriction of rat aorta at normal and high CO2 tensions. AB - Endothelial modulation of norepinephrine (NE)-induced constriction of the isolated rat aorta was studied at normal (PCO2, 41 +/- 0 mmHg) and high CO2 tensions (PCO2, 91 +/- 1 mmHg). In preparations with intact endothelium, increased CO2 tension resulted in rightward shift of the NE dose-response curve with attenuation of maximal contraction. This effect of CO2 was not modified by indomethacin. Treatment with hemoglobin or rubbing of the endothelium meant that increased CO2 tension still resulted in rightward shift of the NE dose-response curve but without altering the maximal contractile response. The basal guanosine 3',5'-cyclic monophosphate (cGMP) levels in control and NE-treated aortic preparations were not affected by increasing the CO2 tension. Thus the inhibitory action of CO2 on NE-induced contraction in the presence of endothelium may not be derived from facilitation of endothelium-derived relaxation factor (EDRF)-induced cGMP synthesis. Increasing the CO2 tension attenuated the sustained contraction induced by the addition of NE and Ca2+ (2.5 mM) to intact endothelium preparations previously bathed in Ca2(+)-free solution. Further addition of Ca2+ (total 5.0 mM) did not increase the contraction. These findings suggest that the intrinsic activity of NE is greatly modified by endothelium at a high CO2 tension. Vasodilation during hypercapnia may be induced at least in part by synergistic actions of EDRF and CO2 on smooth muscle cells. PMID- 2109939 TI - Cardiac chemical reflex control of preload in conscious dogs. AB - The purpose of our study was to determine the effects of cardiac chemical reflexes on left ventricular (LV) preload in conscious dogs. Adult mongrel dogs were instrumented to measure LV pressure and, with ultrasonic dimension crystals, to measure LV internal diameter. A catheter was inserted in the left circumflex coronary artery for the administration of increasing doses of veratridine, arachidonic acid (AA), and prostacyclin (PGI2). LV end-diastolic diameter (EDD) and end-diastolic pressure (EDP) were used as indexes of preload. Veratridine (0.4 micrograms/kg) reduced EDD 3.0 +/- 0.5% from 36.6 +/- 1.7 mm and EDP 24 +/- 5.0% from 6.1 +/- 0.5 mmHg (P less than 0.05). AA (100 micrograms/kg) reduced EDD by 3.7 +/- 0.5% from 37 +/- 1.1 mm and EDP by 25 +/- 4.4% from 7.0 +/- 0.6 mmHg (P less than 0.05). PGI2 (0.5 micrograms/kg) also reduced EDD by 3.3 +/- 0.5% from 37 +/- 0.5 mm and EDP by 25 +/- 6.0% from 7.8 +/- 0.3 mmHg (P less than 0.05). Although holding heart rate constant by pacing or combined beta-adrenergic and muscarinic receptor blockades did not reduce the preload responses to veratridine, AA, or PGI2, alpha 1-adrenergic blockade or vagotomy abolished them. Systemic arterial barodenervation markedly potentiated the reduction in myocardial size after stimulation of cardiac chemical receptors. Stimulation of inhibitory cardiac receptors, therefore, reduces preload via a vagal reflex by withdrawing peripheral alpha-adrenergic tone to capacitance vessels in the conscious dog. PMID- 2109940 TI - Effects of aging on responses of cerebral arterioles. AB - Our goal was to determine whether responses of cerebral arterioles are altered in aged rats. We examined responses of cerebral arterioles in adult (6-8 mo old) and aged (22-24) mo old) Wistar rats to superfusion of acetylcholine and bradykinin, which presumably produce dilatation by releasing an endothelium-derived relaxing factor (EDRF), and to nitroglycerin, which produces dilatation by a direct effect on vascular muscle. In adult rats, cerebral arterioles dilated by 11 +/- 2% (SE) to acetylcholine (10(-5) M) and by 21 +/- 3% to bradykinin (10(-7) M). In contrast, arterioles in aged rats dilated by only 3 +/- 1% to acetylcholine and by 7 +/- 3% to bradykinin. Vasodilatation in response to nitroglycerin was similar to adult and aged rats. We also examined responses of cerebral arterioles to products released by platelets (ADP, serotonin, and thromboxane). ADP (10(-4) M) increased pial arteriolar diameter by 26 +/- 5% in adults rats and only 12 +/- 3% in aged rats. Serotonin (10(-5) M) produced modest vasodilatation in adult rats (7 +/- 1%) but modest vasoconstriction in aged rats (-5 +/- 2%). Vasoconstriction in response to a thromboxane A2 analogue (U 46619) was similar in adult and aged rats. Indomethacin (10 mg/kg iv) did not affect responses to acetylcholine, serotonin, and ADP in aged rats. Thus dilator responses of cerebral arterioles to agonists that may release EDRF are altered in aged compared with adult rats. Impaired vasodilatation in aged rats does not appear to be related to production of a cyclooxygenase constrictor substance. PMID- 2109941 TI - Arachidonic acid causes postischemic dysfunction in control but not diabetic hearts. AB - Isovolumically perfused control and chronic diabetic rat hearts were subjected to 20 min of global ischemia plus 30 min of reperfusion at preischemic flow rates. Recoveries of contractile function during reperfusion were similar in both groups. Addition of arachidonic acid produced profound postischemic dysfunction in nondiabetic hearts (isovolumic minute work = 19 +/- 8 vs. 86 +/- 10% of preischemic levels after 30 min), whereas arachidonic acid had no detrimental effect in diabetic hearts. Arachidonic acid also augmented endogenous prostacyclin release in control hearts (untreated 2.28 +/- 0.23 ng/ml; arachidonic acid 4.07 +/- 0.22 ng/ml) but failed to alter postischemic prostacyclin release in diabetic hearts. The arachidonic acid-induced postischemic dysfunction was significantly attenuated by coadministration of the oxygen free radical scavengers, superoxide dismutase plus catalase, but not by indomethacin. Thus arachidonic acid-induced dysfunction in normal hearts appears to be related, in part, to free radical production. The intrinsic capacity of the heart to synthesize prostacyclin as a result of ischemia and reperfusion does not appear to be impaired by diabetes. In contrast, the arachidonic acid-induced increase in prostacyclin following ischemia is blunted in the diabetic heart. Although chronic diabetic hearts showed increased tolerance to arachidonic acid induced dysfunction during reperfusion, a defect in prostacyclin stimulation may place the diabetic at greater risk of complications of ischemic reperfusion in vivo by reducing the capacity to adequately respond to the aggregatory and vasospastic actions of increased circulating thromboxane consequent to myocardial ischemia and reperfusion. PMID- 2109942 TI - Cerebral blood flow and end-tidal PCO2 during prolonged acetazolamide treatment in humans. AB - One oral dose of 1,000 mg of acetazolamide caused an acute 38% increase in cerebral blood flow (CBF) in eight healthy volunteers. During the following 10 days the subjects took 1,000 mg acetazolamide daily. CBF normalized within the first 2 days. The drug induced mild hyperventilation, gradually decreasing alveolar PCO2 to 70% of the control value at the end of the treatment period. In healthy humans the hyperventilation will not increase brain oxygenation significantly at sea level. But at high altitudes the enhanced ventilatory drive will improve oxygenation of the brain, and this may account for the beneficial effects of the drug on the symptoms of acute mountain sickness. During the treatment there was a significant 10% decrease of the hematocrit but an unaltered hemoglobin concentration. In combination with data in the literature our studies suggest that the initial CBF increase is a consequence of a transient extracellular acidosis dilating brain arterioles, whereas increased ventilatory drive results from a gradually increasing mild intracellular acidosis in the brain. PMID- 2109943 TI - Analysis of short-term oscillations of R-R and arterial pressure in conscious dogs. AB - We studied the neural determinants of the second (i.e., high frequency, HF)- and third-order (i.e., low frequency, LF) spontaneous oscillations of heart period (R R interval) and arterial pressure (AP) in conscious dogs, with the hypothesis that they might furnish quantitative markers of autonomic controlling activities. Spectral analysis of simultaneous R-R and AP variabilities quantified these oscillations that were also evaluated in units normalized by total power to focus on the balance of these two major components. At rest we observed a prevalent HF component (approximately 0.25 Hz) in R-R and AP variabilities that was synchronous with respiration. This HF component of R-R variability disappeared after atropine infusion and can be considered a marker mostly of vagal activity. When baroreceptor unloading, obtained by moderate hypotension, increased sympathetic activity the LF component increased in R-R, systolic, and diastolic AP variabilities. This increase in LF was not present after ganglionic blockade or after chronic arterial baroreceptor denervation. After chronic bilateral stellectomy, hypotension was not accompanied by an increase in LF component of R R variability, while LF component remained in AP variability. An increase in LF component of R-R and AP variabilities was observed during transient coronary artery occlusion. PMID- 2109944 TI - Intranephron PGE2 production in stroke-prone spontaneously hypertensive rats. AB - To investigate whether intranephron prostaglandin E2 (PGE2) production in stroke prone spontaneously hypertensive rats (SHRSP) differs from that in Wistar-Kyoto rats (WKY), we measured PGE2 accumulation rates in microdissected nephron segments from 4- to 6- and 12- to 14-wk-old male rats by radioimmunoassay. In both young and adult WKY, PGE2 accumulation was highest in the papillary collecting duct (PCD) and outer medullary and cortical collecting tubules, intermediate in the glomerulus (Glm), medullary and cortical thick ascending limbs of Henle's loop, and distal tubule, and negligible in the proximal tubule. PGE2 accumulation in adult WKY was severalfold higher than that in young WKY. PGE2 accumulation in adult and prehypertensive young SHRSP was significantly lower than that of respective WKY in most segments, whereas urinary PGE2 excretion was significantly higher in SHRSP than in age-matched WKY. Plasma arginine vasopressin concentrations in adult SHRSP were significantly higher than in WKY. PGE2 accumulation stimulated by 5 microM arachidonic acid was significantly lower in SHRSP than in WKY in most segments of young rats but was lower only in Glm and PCD of adult rats. PGE2 accumulation stimulated by 2 microM Ca2+ ionophore A23187 was significantly lower in most segments of adult and young SHRSP. These results indicate that a decrease in renal tubular PGE2 productive activities in SHRSP might not be caused by secondary adaptation to hypertension. PMID- 2109945 TI - Effect of hematocrit on behavioral thermoregulation of the toad Bufo marinus. AB - This study tested the hypothesis that the oxygen capacity of blood, indexed by hematocrit, affects the body temperature (Tb) selected by toads (Bufo marinus) in a thermal gradient. Anesthetized toads (Brevital sodium; 40 mg/kg im) were fitted with a cloacal thermistor and femoral artery cannula. After recovery, they were placed in a thermal gradient ranging from approximately 10 to 40 degrees C. Tb was measured for 24 h. Then 1-2 ml blood were withdrawn and replaced with an equal volume of either 0.66% saline or packed red cells from donor toads. Selected Tb was measured for the next 24 h. The mean Tb selected by B. marinus (n = 33) was 24.9 degrees C. Cross-sectional analysis showed no correlation between selected Tb and hematocrit. However, each toad rendered anemic showed a reduction of selected Tb (mean = 22.9 degrees C). The degree of Tb reduction was correlated with the hematocrit reduction, (r = 0.86; P = 0.013). Blood doping did not have a significant effect on selected Tb. The reduction of Tb could be adaptive by reducing oxygen consumption. PMID- 2109946 TI - Micropuncture study of the avian kidney: infusion of mannitol or sodium chloride. AB - Renal function was studied in anesthetized starlings by micropuncture and clearance techniques. The effects of intravenous infusions of isosmotic sodium chloride and hyposmotic mannitol solutions were compared. In the proximal tubules of the superficial reptilian-type nephrons, there is net reabsorption of sodium, chloride, and potassium; net secretion of calcium and urate; and either net secretion or no net secretion or reabsorption of magnesium and phosphate. The fractional delivery of ions and urate to the site of micropuncture, the percent of fluid reabsorbed, and the single nephron glomerular filtration rate (SNGFR) were not significantly different between the two infusion treatments. However, in the sodium chloride-infused birds, whole kidney GFR and the fractional excretion of sodium and chloride by the whole animal were higher, and fractional excretion of magnesium and potassium were lower. The data for each infusion group were further subdivided on the basis of whether the birds were in molt. In starlings, molt is associated with elevated levels of plasma prolactin. For the sodium chloride infusion, sodium and water reabsorption to the site of micropuncture was greater in the birds in molt than in those not in molt. PMID- 2109947 TI - A distributed model of fluid and mass transfer in peritoneal dialysis. AB - A mathematical model has been developed to study peritoneal fluid and solute transfer. The model uses the concept of a distributed capillary system within the peritoneal tissue. The model accounts explicitly for transport across the capillary membrane, through interstitial tissue, and across the mesothelium. The capillary and mesothelial membranes are modeled using pore theory and a dual pathway (through pores and across cells) for fluid transfer. The nonperitoneal tissues are modeled as a single body pool. Lymphatic uptake from the peritoneal cavity is included. Model parameters were found from the literature and by simultaneously fitting experimental data for dialysate volume and dialysate concentrations of blood urea nitrogen, glucose, creatinine, and inulin. The model was also shown to predict concentration gradients within several tissues surrounding the peritoneal cavity. Variation of the model parameters revealed the importance of the mesothelial cell layer in peritoneal ultrafiltration. The results of model simulations indicate an initial transfer of fluid from the tissue space to the peritoneal cavity followed by transcapillary fluid transfer. PMID- 2109948 TI - Antibody response to Schistosoma mansoni adult worm cysteine proteinases in infected individuals. AB - Antigens of the Schistosoma mansoni digestive tract are recognized early in the infective process. Two immunogenic components of the excretory/secretory products are proteolytic enzymes that degrade host hemoglobin in the lumen of the parasite gut. These enzymes, CP1 and CP2, belong to the class of cysteine proteinases. In this study, a preparation containing both proteinases has been used to detect proteinase antibodies in the sera of individuals living in Burundi. Of 133 individuals tested, 92% were excreting schistosome eggs. All patients with documented infections had positive anti-proteinase IgG titers (mean = 1:614), while 82% had positive IgM titers (mean = 1:267). Six weeks following praziquantel treatment, patients were assessed for egg excretion and antibody titer. Anti-proteinase IgG titers were significantly lower (mean = 1:259) than pre-treatment titers. Patients who were infected with S. japonicum or S. haematobium typically showed a cross-reactive IgG response. Patients from non endemic regions yielded negative titers, and those with non-trematode parasites were negative (79%) or weakly positive. S. mansoni cysteine proteinases may be used for the detection of schistosome infections. PMID- 2109949 TI - The effect of praziquantel on the circulating antigen SJ 70 in murine schistosomiasis japonica. AB - A circulating schistosome 70 kDa antigen (SJ 70) has been detected in the sera of mice infected with Schistosoma japonicum. For the detection of this antigen, a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed. SJ 70 is first detected in the serum of S. japonicum-infected mice 4 weeks after infection. Antigen levels rise rapidly, plateau by 7 weeks after infection, and remain relatively unchanged for at least another 9 weeks. In mice infected with S. japonicum for 7 weeks and then treated with praziquantel (100 mg/kg body weight), there is a significant decrease in serum antigen levels within 2 weeks after treatment, and an almost complete disappearance of antigen from the serum 3 4 weeks after treatment. PMID- 2109950 TI - Detection of a circulating antigen in human schistosomiasis japonica using a monoclonal antibody. AB - A double antibody enzyme-linked immunosorbent assay (sandwich ELISA) was used for the detection of a circulating antigen from human schistosomiasis japonica infections. This assay involves the use of polyclonal rabbit Schistosoma japonicum soluble egg antigen (SEA) antiserum to bind circulating antigen and a monoclonal antibody (MabH4) to identify and quantify this antigen. Sera from 108 S. japonicum-infected patients (acute and chronic) were tested. Sera from 93 of 95 patients with chronic infection were positive for this antigen; sera from 12 of 13 patients with acute infections were also positive. Antigen was not detectable in control human sera. Sera from 35 chronic schistosomiasis patients were collected 6-12 months after praziquantel treatment. Circulating antigen was not detectable in the sera of 33 of these patients and was dramatically reduced in 2. This ELISA system may prove valuable in differentiating past and current infections. PMID- 2109951 TI - [Sympatho-adrenergic reactions during drug-induced hypotension. A comparative study on probands]. AB - This study was undertaken to compare the influence of different regimens for induced hypotension down to Power a limit of 80 mmHg (systolic) on sympatho adrenergic responses in 10 volunteers. Volunteers were investigated in five batteries of tests using glyceryl trinitrate (10 micrograms/kg BW/min), sodium nitroprusside (10 micrograms/kg BW/min maximal dosage), nifedipine (0.35 micrograms/kg BW/min) and urapidil (bolus injections of 25, 25 and 50 mg, followed by an infusion of 180 ml/h) and placebo. Catecholamines in plasma were detected by HPLC/ECD within a period of 1 h of hypotension and 1 h of recovery at 11 measuring points. Using sodium nitroprusside and glyceryl trinitrate, a significant hypotension was achieved. Urapidil was less potent. No hypotension was observed during or after treatment with nifedipine. Heart rate increased during treatment with sodium nitroprusside and glyceryl trinitrate. Sodium nitroprusside, glyceryl trinitrate and urapidil caused significant rises in noradrenaline levels. With nifedipine, noradrenaline increased within the normal range. Adrenaline left the normal range only during urapidil treatment. MAP, HR, and levels of noradrenaline and adrenaline returned to the initial values 5 min after discontinuation of the sodium nitroprusside infusion. After treatment with glyceryl trinitrate and urapidil, MAP was still low even 60 min after discontinuation of treatment. Urapidil caused marked increases in noradrenaline and adrenaline, which persisted even into the recovery phase. With regard to clinical management and sympatho-adrenergic responses, sodium nitroprusside is the most useful of these compounds for the reduction of hypotension. Having similar potency and active metabolites, glyceryl trinitrate has a longer duration of action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109952 TI - Distribution of laminin in the murine pituitary. AB - The distribution and cellular localization of the glycoprotein laminin were investigated by light and electron microscopic immunocytochemistry in the adult murine pituitary gland. Immunoblots confirmed that laminin was the only protein in the pituitary gland of the adult male mouse to react with antilaminin serum. Laminin immunoreactivity was demonstrated at the light microscopic level simultaneously with that of beta-follicle stimulating hormone (beta-FSH) and beta luteinizing hormone (beta-LH). In addition to its distribution is basal laminae, laminin immunoreactivity was coincidently expressed in gonadotrophs with the immunoreactivities of beta-FSH and beta-LH. Electron microscopic immunocytochemistry was employed on aldehyde-fixed sections embedded in L.R. White. Sites of binding of primary antisera to laminin were identified with affinity-purified secondary antisera directly coupled to 20 nm particles of colloidal gold. Three antisera recognizing laminin were compared and found to result in an identical pattern of immunoreactivity. Laminin was found extracellularly only in formed basal laminae in all three lobes of the pituitary and was not found in extracellular matrices of connective tissue. Laminin immunoreactivity was also found intracellularly in gonadotrophs but in none of the other endocrine or non-endocrine cells of the anterior lobe. Within gonadotrophs, only secretory granules were labeled. The majority, but not all, secretory granules were labeled in each of the gonadotrophs examined, and the proportion of granules labeled with laminin could not be increased by doubling the concentration of anti-laminin serum. Laminin immunoreactivity segregated with the subset of secretory granules containing beta-FSH. In contrast, laminin immunoreactivity was absent in the smaller subset of secretory granules that contain serotonin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109953 TI - The swine steroid 21-hydroxylase gene (CYP21): cloning and mapping within the swine leucocyte antigen complex. AB - A swine genomic cosmid library constructed from a genotypically SLA homozygous Large White individual was screened with a murine genomic 21-hydroxylase probe. A clone which contained a pig 21-hydroxylase gene was isolated and after subcloning, the 5' region of the gene was sequenced. The deduced amino acid sequence corresponded almost exactly to the NH2 terminal portion of the steroid 21-hydroxylase from porcine adrenal microsomes. Comparison of the first 99 amino acid residues of both sequences revealed three substitutions comprising two leucine residues in positions 10 and 13, and one arginine residue in position 55 for our sequence, instead of threonine in position 10 and lysine in position 13 and 55 for the isolated enzyme. A swine homologous probe was derived from the isolated 21-hydroxylase gene and used for gene assignment by RFLP studies in two swine leucocyte antigen (SLA) informative families. The results demonstrate that the swine 21-hydroxylase gene is located within or close to the swine MHC. Taken together, the present results suggest the existence of a single 21-hydroxylase gene per haploid genome. PMID- 2109954 TI - Variation in T cell responses to ovalbumin in cattle: evidence for Ir gene control. AB - Genetic control of immune responsiveness in cattle was investigated using an antigen-dependent T cell proliferation assay in vitro. Bovine T cell proliferative responses to ovalbumin were dependent upon major histocompatibility complex (MHC) class II molecules. Responses of an unrelated panel of animals to a limiting concentration of ovalbumin after a single immunization were compared. Two discrete patterns of response were observed. One group of animals had low or non-responses which were not significantly different from the preimmune levels. Another group of animals showed significant responses. After a second immunization the majority of low responders remained low responders. There was no significant correlation between bovine MHC class I BoLA haplotype and magnitude of response within this group of unrelated animals. However, the magnitude of the T cell responses by two half-sib family groups segregated with BoLA haplotypes inherited from the sire. In contrast no significant correlation with antibody responses in vivo could be demonstrated. We suggest that the observed variation in T cell response is linked to bovine MHC class II immune response (Ir) genes. PMID- 2109955 TI - Swine lymphocyte alloantigens (SLA) class I serology and genetics in Belgian Landrace and Pietrain breeds. AB - Eighty anti-SLA class I reagents were prepared resulting from skin graft and subcutaneous immunizations in 320 fattening pigs of the Belgian Landrace and Pietrain breeds. By means of these alloantisera seven internationally and five locally established specificities were recognized. Three of the locally assigned specificities were new: BM 36, BM 37 and BM 38. They were serologically and genetically defined. The typing battery was completed with French and Danish reagents, and correlation coefficients were calculated for the main alloantisera recognizing SLA class I alloantigens observed in the Belgian breeds. The SLA haplotype frequencies were estimated in 372 Belgian Landrace and 369 Pietrain pigs. The SLA haplotype distribution differs significantly between both breeds and the genetic distance (0.54) at the SLA system is quite high. PMID- 2109956 TI - The definition of five B lymphocyte alloantigens closely linked to BoLA class I antigens. AB - B lymphocyte alloantigens in cattle were identified by serological analysis. Alloantisera were raised by skin implant immunization or leucocyte immunization and were absorbed with platelets to reduce class I-specific antibody activity. Leucocyte absorptions were done to reduce the complexity of some antisera. A panning technique was used to prepare B-enriched and B-depleted lymphocytes. Antisera which displayed anti-B cell activity over a number of dilutions were tested against 115 Charolais cattle, and 13 antisera were used to define five B lymphocyte alloantigens. These antigens were present on B lymphocytes but did not appear to be present, at least at the same density, on the majority of T lymphocytes or platelets. Family studies suggested that these antigens are coded by one or two loci which are closely linked to the bovine class I loci. These results suggest the five antigens are class II antigens of the major histocompatibility complex (MHC) of cattle. PMID- 2109957 TI - [Respiratory effects of almitrine on various levels of the fraction of inspired oxygen. A study in the anesthetized dog]. AB - The effects of intravenous almitrine under normoxic, hyperoxic, and hypoxic conditions were studied in 5 male beagle dogs (mean weight 15.2 +/- 5 kg) anaesthetized with thiopentone. Plasma concentrations of thiopentone were maintained constant at 27-29 mg.1(-1). Each animal underwent twice the three different experiments, with a lapse of a fortnight between each experiment: a) breathing room air, with intravenous administration of 1 mg.kg-1 almitrine over 30 s, b) breathing room air, then pure oxygen for 15 min, followed by an intravenous administration of 1 mg.kg-1 almitrine over 30 s with the dog still breathing pure oxygen, and c) breathing room air, then progressively less oxygen (FIO2 0.18, 0.16, 0.14, 0.12 for 5 min each), followed by an intravenous administration of 1 mg.kg-1 almitrine over 30 s with the dog still breathing a mixture with 12% oxygen. Tidal volume, respiratory rate, minute ventilation, inspiratory and expiratory duration, arterial pH, PaO2 and PaCO2 were measured respectively in room air, after 100% oxygen, in hypoxia (FIO2 = 0.12), before, 5 and 10 min after the injection of almitrine. Hyperoxia depressed ventilation ( 21%), whilst hypoxia stimulated it (+126%), although significantly less than in the awake animal. Almitrine restored the respiratory response to hypoxia, but hyperoxia did not suppress respiratory stimulation due to the drug. It would therefore seem likely that almitrine acts on peripheral arterial chemoreceptors, but also on other structures. The results of this study suggest that almitrine may be useful in restoring the respiratory response to hypoxia during recovery from anaesthesia. PMID- 2109958 TI - [Flumazenil and peroperative awakening in surgery of scoliosis]. AB - Motor and sensory function must be assessed during surgery of scoliosis so as to avoid possible damage to the spinal cord. The intraoperative awakening by a specific benzodiazepine antagonist, flumazenil, was studied prospectively in 20 patients (mean age 17 years) undergoing surgery for severe scoliosis. Premedication consisted in 0.02 mg.kg-1 atropine and 0.15 mg.kg-1 midazolam. Anaesthesia was induced with a mean dose of 0.42 +/- 0.1 mg.kg-1 midazolam, 1.6 +/- 0.6 micrograms.kg-1 fentanyl and 0.1 mg.kg-1 pancuronium. Maintenance was obtained with a continuous infusion of 0.22 +/- 0.1 mg.kg-1.h-1 midazolam, 66% nitrous oxide in oxygen, and fentanyl (1.6 +/- 0.5 micrograms.kg-1.h-1). Nitrous oxide and midazolam were respectively stopped 10 and 1 min before giving the antagonist (5 micrograms.kg-1 flumazenil) if required (17 out of the 20 patients). Eye opening occurred a mean 42 +/- 32 s after giving the antagonist. At this time, there was a significant increase in mean arterial blood pressure (+ 11 mmHg) and heart rate (+ 7 b.min-1). Thiopentone, 66% nitrous oxide in oxygen and 0.5% halothane were given to re-induce and maintain anaesthesia for completion of the procedure. The day following surgery, 19 patients were unable to remember the period of intraoperative awakening. One patient, although remembering the episode, did not experience any pain or any other disagreement in relation to it. Two patients were given a second dose of flumazenil at extubation so as to improve the quality of their recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109959 TI - Differences in air ambulance patient mix demonstrated by physiologic scoring. AB - Severity of illness or injury should be the primary justification for aeromedical transport. To determine whether differences in patient severity were detectable in air transport programs, helicopter-transported patients were examined by three established physiologic scores: the Trauma Score, the Acute Physiology and Chronic Health Evaluation Score, and the Rapid Acute Physiology Score. These scores were obtained prospectively on 1,868 consecutive patient transfer requests from six air medical services for periods ranging from two to six months. A patient meeting strict physiologic criteria was considered critically ill. Overall, 42.6% of the patients (range, 34.8% to 53.3%) were considered critically ill. Patients transported from inpatient hospital units and patients with cardiac disease were less likely to be critically ill than those transported emergently from scenes of accident or from emergency departments. There were also significant differences between programs with regard to the percentage of critically ill patients transported. This study suggests that physiologic scoring may be useful in comparing air ambulance programs and that a majority of patients transported by these services may not be critically ill. PMID- 2109960 TI - The prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis in victims of sexual assault. AB - The prevalence of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in 232 sexual assault victims who presented for examinations between August 1, 1987, and July 31, 1988, was determined. Results are reported for cervical, rectal, and oropharyngeal NG cultures and for cervical and rectal CT smears. Results from a one-week follow-up are also reported. Cervical test results from the initial sexual assault examination were compared with cervical tests on 399 randomly selected female emergency department patients who presented for other gynecological conditions or lower abdominal pain. The victims of sexual assault had ten of 210 positive cervical NG cultures (4.76%), and 13 of 213 positive cervical CT smears (6.1%) at the first visit. These prevalence rates were not significantly different (P = .3058). There were none of 28 positive rectal NG cultures (0%) and one of 22 positive rectal CT smears (4.34%) (P = .451). None of the 43 oral NG cultures was positive. Seventy-three victims returned for follow up examination. No follow-up cervical, rectal, or oral NG cultures were positive. However, one of 53 follow-up cervical smears for CT was positive, but this was not significantly different than for cervical NG (P = .461). Sexually assaulted patients had ten of 210 (4.76%) cervical NG cultures positive, and nonassaulted patients showed 53 of 393 positives (13.4%) (P less than .001). Assaulted patients had 13 of 213 (6.1%) cervical CT smears positive, and nonassaulted patients showed 33 of 352 (9.3%) positives (P = .11).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109961 TI - Cost-effectiveness: asserted, not shown. PMID- 2109962 TI - Screening for hypertension. PMID- 2109963 TI - Lactose intolerance. AB - Lactose intolerance is a prevalent clinical problem. Low lactase levels result either from intestinal injury, or as in the majority of the world's adult population, from alterations in the genetic expression of lactase-phlorizin hydrolase. Progress is being made in the basic understanding of the molecular and cellular biology of this enzyme and of the scientific basis of clinical syndromes involving low lactase activity. PMID- 2109964 TI - G protein mediated regulation of K+ channels in heart. PMID- 2109965 TI - GE: a GTP-binding protein mediating exocytosis. PMID- 2109966 TI - Photochemical manipulation of divalent cation levels. PMID- 2109967 TI - Polychlorobiphenyl (PCB) congeners in striped bass (Morone saxatilis) from marine and estuarine waters of New York State determined by capillary gas chromatography. AB - Edible filets of striped-bass samples (60) from the Hudson River estuary, the Atlantic shore of Long Island, and Long Island Sound were analyzed by high resolution glass-capillary gas chromatography for 74 polychlorobiphenyl (PCB) compounds. The fish, a non-random subset of a larger sample, contained the following concentrations of total PCB residue (mean +/- the standard error of the mean). The corresponding mean values for the entire survey (N = 717) are given in parentheses: eastern Long Island Sound 1.8 +/- 0.4 (1.91 +/- 0.1) mg/kg; western Long Island Sound, 1.9 +/- 0.2 (2.51 +/- 0.1) mg/kg; eastern Atlantic shore, 3.0 +/- 0.5 (2.45 +/- 0.2) mg/kg; western Atlantic shore, 7.5 +/- 1.9 (3.04 +/- 0.2) mg/kg; Hudson River, 15 +/- 3 (6.19 +/- 0.4) mg/kg. All the samples contained PCB residues derived from Aroclors 1242, 1016, 1254, and 1260 but none of the residue present came from Aroclor 1221 as evidenced by the complete absence of 4 chlorobiphenyl from the fish. Fish from the Hudson River and the majority from the Atlantic shore of Long Island contained 2,2'- and 2,6-dichlorobiphenyls indicating recent exposure to Hudson River PCBs. On this basis, there was evidence that a subpopulation of fish was not exposed to the Hudson River PCB source. The detailed PCB congener make-up of the typical residue found in these fish differs from that found in the majority of human food-stuff in that it contains a proportionately large amount of mono- through tetra-chlorinated PCB. The mean concentration of the more toxicologically suspect congeners which are not readily degraded by mammals and birds (those with two 4-substituents) comprise less than 1 ppm in Long Island Sound fish. PMID- 2109969 TI - Residency training in long-term care settings. PMID- 2109968 TI - Mixed Schistosoma haematobium/Schistosoma intercalatum infection. PMID- 2109970 TI - Rapid cycling bipolar affective disorder. I. Association with grade I hypothyroidism. AB - Thirty patients with rapid cycling bipolar affective disorder were studied prospectively to assess presence and severity of thyroid hypofunction. Seven (23%) were classified as having grade I hypothyroidism, while 8 (27%) had grade II and 3 (10%) had grade III abnormalities. This prevalence of grade I hypothyroidism is significantly greater than that reported in studies of unselected bipolar patients during long-term treatment with lithium carbonate, although only 63% of this sample of rapid cycling patients was taking lithium carbonate or carbamazepine. The association of rapid cycling with grade I hypothyroidism cannot be accounted for by lithium carbonate use or by the preponderance of women among rapid cycling patients. These findings (1) indicate that hypothyroidism during bipolar illness is a risk factor for the development of rapid cycling, and (2) leads to the hypothesis that a relative central thyroid hormone deficit occurring in bipolar patients predisposes to a rapid cycling course. PMID- 2109971 TI - Difference between evening and morning thyrotropin responses to protirelin in major depressive episode. AB - We studied the thyrotropin response to protirelin challenge (200 micrograms intravenously) at 8 am and at 11 pm after a minimum washout period of 10 days in 29 euthyroid inpatients who met DSM-III-R criteria for major depressive episode and 20 normal volunteer controls. The maximum increment in thyrotropin above baseline (delta thyrotropin) was significantly greater at 11 pm than at 8 am both in patients and in controls. However, the difference between 11 pm delta thyrotropin and 8 am delta thyrotropin (delta delta thyrotropin) was significantly lower in patients than in controls. The lower delta delta thyrotropin found in patients could not be explained by differences in age, body weight, sex, or thyroid functioning. In the overall population, delta delta thyrotropin correlated with circadian variables (ie, mesor and amplitude). With the use of a criterion of less than 3 mU/L to define a blunted delta delta thyrotropin, the diagnostic sensitivity was 89% and the specificity was 95%. We suggest that delta delta thyrotropin has the advantage of taking into account chronobiologic influences in the interpretation of the protirelin/thyrotropin challenge, and this may explain the improved diagnostic value derived from this measure in the diagnosis of major depressive episode. PMID- 2109972 TI - Autoradiography of hypothalamic regions after acute hyperosmolarity in mice. AB - Many regions around the third ventricle of the brain are thought to participate in the regulation of water intake. In this study we have visualized in acutely hyperosmolar mice the hypothalamic regions by using autoradiography and [14C]deoxyglucose as marker. By applying a recently published, inexpensive, calibrated photographic method for the analysis of the autoradiographs, we can show that the medial parts of the hypothalamus near the third ventricle increased their uptake of deoxyglucose in comparison with the lateral parts. Densitometric measurements confirmed the results. The results also indicate that parts of the medial hypothalamus, even those that are more caudal than the paraventricular nuclei, react to hyperosmolarity. PMID- 2109974 TI - Cost effective job placement physical examinations. A decision making framework. AB - 1. Job placement physical examinations are performed to match the worker's physical capabilities with the anticipated job assignment. A careful analysis of the work setting and company philosophy should be done prior to structuring a program for job placement examination. These examinations also provide valuable baseline data. 2. Components of the examination should be tailored to the specific work setting and the identified purposes for performing job placement examinations. Job analysis, careful history taking, physical examination, and laboratory and specialized testing are common aspects. 3. Results obtained in the job placement examination program should be handled carefully and ethically to comply with government regulations and legal implications. PMID- 2109973 TI - Intra-habenular injection of 6-hydroxydopamine produces impaired acquisition of DRL operant behavior. AB - The anatomical connections of the habenula complex indicate it provides a relay between limbic forebrain and midbrain. Somewhat paradoxically, consequences of nonspecific lesion of the habenula are ambiguous with little change in basic response evident within simple behavioral paradigms. However, the potential functional importance for this relay has more recently been indicated by the demonstration of deficits in the ability of lesioned animals to alter behavior appropriate to both internal and external stimuli in more demanding behavioral tasks. Doubts concerning the importance of the habenula remain because of the large number of descending fibers of passage through the habenula. To provide more substantive evidence, 6-hydroxydopamine was injected into the habenula of rats to provide more limited lesion of catecholaminergic terminals. Animals were subsequently trained on an operant DRL 20-s schedule for which deficits have been reported following nonspecific lesion of the habenula. Lesioned animals showed a tendency to overrespond and were significantly less efficient on the schedule with decreased number of reinforcements received relative to controls. While the neurotoxic lesion procedure used does not differentiate noradrenergic and dopaminergic damage, the importance of intact catecholaminergic systems within the habenula for effective DRL acquisition is consistent with the suggested importance of the habenula for feedback regulation of dopamine within the ventral tegmental area through ascending dopamine fibers to the habenula. PMID- 2109975 TI - Myoclonic seizures are usually seen in patients who have some anoxic and/or toxic metabolic encephalopathy. PMID- 2109976 TI - Phrenic nerve damage in the tiny infant during vein cannulation for parenteral nutrition. AB - An infant weighing 740 gm at birth underwent right internal jugular venous cannulation for the administration of parenteral nutrition at age 17 days. The roentgenogram obtained to assess catheter placement revealed a high right diaphragm for the first time in the course of the infant. The phrenic palsy was incurred during the cutdown in the neck of the tiny, then 650 gm, infant. Two similar patients are mentioned in the literature. The phrenic palsy appeared to delay improvement in the respiratory status of this infant. This patient illustrates the fact that phrenic nerve palsy is a potential complication of central line placement in the neck of a very low birthweight infant. PMID- 2109977 TI - Umbilical cord blood gases for term healthy newborns. AB - Examination of paired umbilical arterial and umbilical venous blood gases for 147 term, healthy newborns revealed a strong correlation of pH, bicarbonate, and base excess with the 1-minute Apgar score. Although significantly different from each other, a strong correlation existed between the gas measurements of the two vessels. The lower limit of pH for the umbilical artery was 7.12 and for the vein, 7.25. The arterial-venous difference for bicarbonate but not pH, oxygen or carbon dioxide tension, or base excess was correlated with the 1-minute Apgar score. PMID- 2109979 TI - Increase of the relative frequency of penicillinase-producing Neisseria gonorrhoeae strains to more than five per cent in Munich. AB - The relative frequency of penicillinase-producing Neisseria gonorrhoeae strains isolated from Munich STD patients nowadays clearly exceeds five percent. Penicillin resistance is either due to the 3.2 or 4.4 Megadalton plasmid. Similar trends are reported from other European countries. Therefore, treatment with third generation cephalosporins such as ceftriaxone, cefotaxime or others is now generally advisable not only in the Far East and Central Africa but also in Central Europe. PMID- 2109978 TI - Properties of purine nucleoside phosphorylase (PNP) of mammalian and bacterial origin. AB - Purine nucleoside phosphorylase (PNP), from calf spleen, human erythrocytes and E. coli have been examined with regard to structural requirements of substrates and inhibitors. Kinetic parameters (Km, Vmax/Km) for a variety of N(1) and/or N(7)-methylated analogues of guanosine, inosine and adenosine have been evaluated for all three enzymes. The substrate and/or inhibitor properties of purine riboside, 1,6-dihydropurine riboside, some deazapurine nucleosides: 3-deaza- and 7-deazainosine, 1,3-dideazapurine riboside (ribobenzimidazole), and a variety of acyclonucleosides, have been determined with mammalian and bacterial enzymes. Overall results indicate distinct similarities of kinetic properties and structural requirements of the two mammalian enzymes, although there are some differences as well. The N(1) and O6 of the purine ring are necessary for substrate-inhibitor activity and constitute a binding site for the mammalian (but not the bacterial) enzymes. Moreover, nucleosides lacking the N(3) undergo phosphorolysis and those lacking N(7) are inhibitors (but not substrates). Methylation of the ring N(7) leads to two overlapping effects: labilization of the glycosidic bond, and impediment to protonation at this site by the enzyme, a postulated prerequisite for enzymatic phosphorolysis. It is proposed that a histidine interacts with N(1) as a donor and O6 as an acceptor. Alternatively N(1)-H and C(2)-NH2 may serve as donors for hydrogen bonds with a glutamate residue. The less specific E. coli enzyme phosphorolyses all purine ring modified nucleosides but 7-deazainosine which is only an inhibitor. On the other hand, the bacterial enzyme exhibits decreased activity towards N(7)-methylated nucleosides and lack of affinity for a majority of the tested acyclonucleoside inhibitors of the mammalian enzymes. The foregoing results underline the fundamental differences between mammalian and bacterial enzymes, including variations in the binding sites for the purine ring. PMID- 2109981 TI - [Current status of maintenance therapy in ulcer disease]. PMID- 2109980 TI - Gastrin, motilin and pancreatic polypeptide levels after two different parenteral regimens in infants. AB - We studied the effect of 2 different parenteral regimens upon gastrin, motilin and pancreatic polypeptide (PP) levels in infants. In 15 children, aged 1-25 months, plasma peptide levels were measured by radioimmunoassay in the fasting state and after a 2-h infusion of either a mixture of amino acids, glucose and lipids (A) or a mixture of amino acids and glucose (B) only. Wide interindividual fluctuations were noted, especially for motilin and PP, but, except for PP, intraindividual fluctuations were low. Indeed, a good correlation was found, not only between the 2 pre-infusion levels, but also between pre- and postinfusion levels in both experiments. In fact for all 3 peptides, pre- and postinfusion levels differed only slightly and non-significantly. We conclude that during parenteral feeding levels of motilin, PP and gastrin remain practically unchanged and are not influenced by the addition of lipids. In addition, during the observation period basal levels did not change, indicating that the mechanisms regulating basal secretion were not affected. PMID- 2109982 TI - Enzymatic production of L-tryptophan from DL-serine and indole by a coupled reaction of tryptophan synthase and amino acid racemase. AB - Enzymatic production of L-tryptophan from DL-serine and indole by a coupled reaction of tryptophan synthase and amino acid racemase was studied. The tryptophan synthase (EC 4.2.1.20) of Escherichia coli catalyzed beta-substitution reaction of L-serine into L-tryptophan and the amino acid racemase (EC 5.1.1.10) of Pseudomonas putida catalyzed the racemization of D-serine simultaneously in one reactor. Under optimal conditions established for L-tryptophan production, a large-scale production of L-tryptophan was carried out in a 200-liter reactor using intact cells of E. coli and P. putida. After 24 h of incubation with intermittent indole feeding, 110 g liter-1 of L-tryptophan was formed in molar yields of 91 and 100% for added DL-serine and indole, respectively. Continuous production of L-tryptophan was also carried out using immobilized cells of E. coli and P. putida. The maximum concentration of L-tryptophan formed was 5.2 g liter-1 (99% molar yield for indole), and the concentration decreased to 4.2 g liter-1 after continuous operation for 20 days. PMID- 2109983 TI - Optimization of enzyme-mediated peptide bond formation. AB - Enzyme-catalyzed peptide bond formation requires thorough examination and optimization of each coupling step. In order to identify factors influencing the selectivity between aminolysis and hydrolysis, a systematic study was carried out for the kinetically controlled peptide synthesis. The reaction temperature, the type of C-terminal protecting group, and different organic cosolvents showed little influence on the selectivity. The enzyme, excess nucleophile, pH, N terminal protecting group, and ionic strength of the solution were identified as major factors controlling the selectivity and, therefore, the yield of the dipeptide synthesis. Under optimized conditions, the selectivity of the chymotrypsin-catalyzed synthesis of PheSer could be increased from 35 to 100%. PMID- 2109984 TI - Impairment of the regulation of gonadal function in Channa punctatus by metacid 50 and carbaryl under laboratory and field conditions. AB - Regulation of gonadal function by gonadotropic hormone (GtH) and gonadotropin releasing hormone (GnRH) in Channa punctatus was significantly affected by nonlethal levels of Metacid-50 and Carbaryl. Under laboratory conditions, the time-dependent decrease in serum GtH level was higher in Carbaryl-treated fish than in Metacid-50-treated fish. The situation was reversed in the field, with a higher inhibitory effect of Metacid-50 being recorded. On the other hand, pituitary GtH content and GnRH activity were inhibited to a greater extent by Metacid-50 than by Carbaryl under both field and laboratory conditions. The present findings highlight that even low doses of Metacid-50 and Carbaryl are effective enough to cause reproductive damage, as evidenced by homeostatic unbalance of the reproductive regulatory system. PMID- 2109985 TI - Interaction between aluminum and zinc or copper and its effects on the pituitary testicular axis. II. Testicular enzyme and serum gonadotropin assay. AB - Sprague-Dawley male rats were divided into groups and maintained on a semipurified diet containing either 5 or 40 ppm of zinc or 2 or 8 ppm of copper. Half of the rats in each group received 1000 ppm aluminum in the diet. It was found that aluminum accumulated in the pituitary glands and testes when dietary copper levels were suboptimal. The ALP activity in testes was depressed by the added aluminum when the intake of zinc or copper was suboptimal. SDH, LDH, and LDH-X activities were inhibited and GRS and GGTP activities were elevated in rats fed either the suboptimal zinc or copper diet. However, the added aluminum in the diet reversed the changes to normal levels. The testosterone levels in plasma changed very little when the zinc or copper intake was suboptimal. An increase in plasma FSH was demonstrated in groups of both suboptimal zinc and copper intake. But the plasma LH was elevated only in the group receiving the suboptimal copper diet, and the added aluminum reversed plasma LH to control levels. A lower level of testosterone was demonstrated in the group given suboptimal copper with aluminum. It was concluded that dietary aluminum influenced the pituitary testicular axis by interacting with certain essential trace metals, particularly zinc. PMID- 2109986 TI - Effect of selenium on aflatoxin hepatocarcinogenesis in the rat. AB - The effects of selenium (Na2SeO3) on aflatoxin B1 (AFB1)-induced hepatic neoplasia were studied in the rat. Putative preneoplastic foci and nodules composed of basophilic, eosinophilic, and clear cells developed early. Basophilic foci were seen first; in the later stages basophilic and eosinophilic nodules predominated. At each stage the AFB1 + Se groups showed fewer and smaller foci and nodules than the AFB1 - Se group. The number of foci in the AFB1 + 3 ppm Se group and their mean area were smaller than those in the 6 ppm Se + AFB1 group. At the end of the experiment hepatocellular carcinoma (HCC) was found in 11/18 rats (61%) of the AFB1 - Se group. HCC was not found in either of the groups given AFB1 + Se. We conclude that Se had an inhibitory effect on the initiation and promotion stages of AFB1-induced preneoplastic foci and nodules. Se also prevented progression of these nodules to HCC even after cessation of AFB1 administration. The inhibitory effect of Se at 3 ppm was greater than at 6 ppm. The 6 ppm Se group also showed evidence of toxicity. PMID- 2109987 TI - Pseudoarthrosis in heterotopic ossification in spinal cord-injured patients. AB - Heterotopic ossification (HO) of proximal joints is a common complication of spinal cord injury, traumatic brain injury, and burns, and is also seen among an array of other clinical conditions. Of the patients with HO, 3-8% develop ankylosis of the joint involved. Although the etiology of HO is not known, the main goal in its management is to retain the maximum possible functional range of movement in the joint involved. Toward this end, surgical resection of HO with etidronate disodium treatment to mobilize ankylosed joints has been reported, as has forceful joint manipulation in head-injured adults with HO. This paper presents two cases of extensive HO formation around hip and knee joints in patients who developed pseudoarthrosis. Cinradiographic assessment of the joints involved revealed pseudoarthrosis formation at the same axis as the normal anatomical plane of the joint, thus permitting functional range of movement. PMID- 2109988 TI - Lactic acid bacteria and human health. AB - Although claims for health and nutritional benefits have been made for lactic acid bacteria in fermented dairy products for nearly a century, the nutritional and therapeutic value of these organisms is still controversial. This article will review the scientific basis of these claims. There are numerous studies showing fermentation of food with lactobacilli increase the quantity, availability, digestibility, and assimilability of nutrients. The basis for this conclusion comes from direct measurements of vitamin synthesis and from increased feed efficiency when fermented products are fed to animals. There have been a number of studies showing that various fermented dairy products lower serum cholesterol levels in humans and animals. These studies are reviewed and the validity of these findings are assessed. A summary of the evidence indicating that lactase deficient individuals can eat yogurt and the mechanisms involved in this toleration is reviewed. The role of fermented dairy products in inhibiting tumor growth and chemically induced tumors in animals is discussed and the possible mechanisms involved in this protective effect are reviewed. Fermented dairy products and lypholized lactobacilli preparations have been shown to be useful in treating and preventing various intestinal infections including; salmonellosis, shigellosis and antibiotic induced diarrhea. In this context a specific lactobacillus designated GG has been shown to be useful in treating recurring diarrhea caused by a toxin produced by Clostridium difficile. PMID- 2109989 TI - Effect of antibodies to human seminal plasma inhibin on spermatogenesis and sperm agglutination in adult male rats. AB - In vitro incubation of rat epididymal sperm with antiserum to human seminal plasma inhibin (As hSPI) caused agglutination of the sperm. In vivo administration of As hSPI to adult male rats resulted in a significant decrease in testicular as well as epididymal sperm counts. Furthermore, the majority (almost 90%) of the epididymal sperm were agglutinated. When these animals were mated with normal cycling females, significant reduction in fertility was observed. PMID- 2109990 TI - Assessment of the human sperm acrosome reaction using concanavalin A lectin. AB - A method for assessment of the human sperm acrosome reaction is reported using fluorescein isothiocyanate (FITC)-conjugated Concanavalin A (ConA). The technique involved labelling prefixed spermatozoa, where only those spermatozoa that showed a complete loss of the acrosome bound FITC-ConA to the acrosomal region. Competitive sugar binding studies demonstrated that binding of ConA lectin to the acrosomal area of human spermatozoa was inhibited in the presence of 0.2 M D mannose. Staining with the supravital stain Hoechst 33258 (H258) concomitantly with FITC-ConA allowed determination of only those spermatozoa that had undergone a true and not degenerative acrosomal loss. Incubation of human spermatozoa with 0, 1, 5, and 25 microM calcium ionophore, A23187, for 60 min demonstrated that changes in acrosomal status due to the different treatment protocols may be determined by the dual-staining method. Electron microscopy studies revealed that gold-conjugated ConA bound specifically to the surface of the inner acrosomal membrane of acrosome-reacted spermatozoa. A significant correlation (r = +.97) between transmission electron microscopy (TEM) and FITC-ConA labelling methods of acrosomal status assessment was achieved. The simple ConA labelling procedure reported here therefore provides a reliable method for quantitation of the physiological acrosome reaction of a population of human spermatozoa. PMID- 2109991 TI - Cleavage development of bovine oocytes fertilized by sperm injection. AB - Whole in vitro capacitated bovine spermatozoa were microinjected directly into the ooplasm of in vitro matured bovine oocytes in order to determine whether oocytes fertilized by sperm injection could undergo normal pronuclear formation and cleavage development. Immature oocytes recovered from follicles (2-5 mm) of unstimulated ovaries were cultured for 24-25 h in modified TCM 199 medium supplemented with heat-treated day 20 cow serum, luteinizing hormone (LH), and estradiol 17-B. In vitro capacitated, frozen-thawed spermatozoa were injected into the ooplasm, and the injected oocytes were cultured for an additional 24-28 h. Twenty-one percent (21/101) of the sperm-injected oocytes contained a sperm within the ooplasm; however, only 2% (2/101) cleaved. The remaining oocytes either did not contain a sperm or had degenerated. After oocyte activation induced by a 5 min incubation in 1 microM A23187, sperm nuclear decondensation occurred in the A23187-activated, injected oocytes but not in the unactivated, injected controls (37% vs. 0% after 3 h). Those injected, activated oocytes that contained a male pronucleus also exhibited a female pronucleus and second polar body. Furthermore, a significantly higher number (28%, 6/21) of the injected, activated oocytes cleaved to a two- to four-cell stage after 48 h than did the injected, unactivated oocytes (4%). These results indicate that, unlike hamster and rabbit oocytes, bovine oocytes are not sufficiently stimulated by the injection procedure to complete meiosis, but, upon activation by calcium ionophore, they will undergo normal-appearing cleavage development following fertilization by sperm injection. PMID- 2109992 TI - [Aspects of antiepileptic drug therapy in children]. AB - During the past 10 years, better results in the treatment of epilepsy have been obtained through the application of pharmacokinetic data to drug therapy of epilepsy. However, pediatric drug therapy is complicated by the continuous change in body weight and body composition with the growth and development, especially during infancy. Younger children require a higher dose per kilogram of body weight than older children in order to achieve comparable plasma concentrations. Plasma levels and seizure control were investigated in a prospective randomized study when phenytoin, carbamazepine (CBZ) or sodium valproate (VPA) was given as a single drug to pediatric patients with several types of epileptic seizures. Studies on newly referred, previously untreated children suggest that both partial and generalized tonic-clonic seizures can be prevented by each of the three drugs. No significant differences in clinical efficacy were found among the three drugs, when optimum plasma concentration ranges were maintained with blood level monitoring. Clonazepam (CZP) may be effective in partial seizures. However, as a wide range of plasma levels was associated with complete freedom from seizures, it was not possible to define a therapeutic range for CZP. Any patient who receives multiple-drug therapy is at risk to develop a drug-drug interaction. Simultaneous administration of VPA was associated with a raised plasma level of carbamazepine-10,11-epoxide (CBZ-E), a major metabolite of CBZ, relative to the CBZ dose, whereas the plasma CBZ level remained unaltered. High plasma concentration of CBZ-E may be responsible for side effects in some patients. Drug protein binding interactions are another source of side effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2109993 TI - [Immunoglobulin class and light chain type of oligoclonal bands in CSF in children with CNS infectious diseases]. AB - Agarose gel electrophoresis and immunofixation of CSF and serum from 16 patients aged from 1 day to 13 years with CNS infectious diseases (5 with purulent meningitis, 5 with aseptic meningitis, 4 with acute encephalitis, 1 with subdural empyema and 1 with SSPE) revealed oligoclonal IgG bands in 10 cases. In 4 cases, a high CSF/serum albumin ratio was recognized without an increase of IgG-index, probably representing a systemic immune response. Neither IgA nor IgM bands were recognized. IgG light chain was examined in 7 cases and IgG kappa bands predominated in 6 cases. IgG lambda bands predominance presented in only one case. Free IgG kappa or lambda chain was not found. These results suggested that the measurement of not only IgG-index but oligoclonal bands may have a diagnostic usefulness to know about local production of immunoglobulins in CSF. PMID- 2109994 TI - [Case report of neuronal ceroid lipofuscinosis: muscle biopsy and TRH treatment]. PMID- 2109995 TI - Effect of ethane-I-hydroxy-I, I-diphosphonate on arterial calcinosis induced by hypervitaminosis D: a morphologic investigation. AB - The present study was undertaken to examine changes in vascular ultrastructure of rats subjected to hypervitaminosis D with or without treatment with ethane-I hydroxy-I, I-diphosphonate (EHDP). Five groups of rats were studied. Untreated rats were given 0.9% NaCl i.p. Sham-treated rats were given vehicle (corn oil). Treated rats were given ergocalciferol (75,000 IU i.p.) dissolved in vehicle with or without EHDP (5 mM/100 g body-weight i.p.). Rats which had been given ergocalciferol without EHDP developed hypercalcemia and demonstrated significant arterial calcinosis. A similar degree of calcinosis was not observed in rats given ergocalciferol with EHDP. EHDP appeared to inhibit arterial calcinosis; however, it did not affect plasma calcium levels. This suggests that EHDP might delay calcium influx into the cell and thereby prevent calcium overload. Our findings support the suggestion that EHDP therapy can be an effective treatment for the inhibition of dystrophic arterial calcinosis. PMID- 2109996 TI - Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial. AB - A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty. PMID- 2109997 TI - Recombinant gamma interferon provokes resistance of human breast cancer cells to spontaneous and IL-2 activated non-MHC restricted cytotoxicity. AB - Natural and lymphokine activated killer cells (NK and LAK) are believed to play an important role in the control of tumour progression and metastasis. Their specific receptors on tumours cells are still unknown. Several studies suggest that these cells recognise and eliminate abnormal cells with deleted or reduced expression of MHC class I molecules. Previous reports suggest that interferons (IFN), by increasing MHC class I expression on target cells, induce resistance to killing by NK cells. We investigated the role of MHC molecule expression by two human breast cancer cell lines T47D and ZR75-1 in their susceptibility to NK and LAK cells. These two cell lines spontaneously express low levels of HLA class I antigens but no HLA class II molecules. After IFN-gamma treatment they both overexpressed MHC class I and de novo expressed class II molecules as detected by flow cytometry, quantified by a radioimmunoassay and analysed by two-dimensional gel electrophoresis. Opposed to untreated cells these IFN-gamma treated cells were resistant to NK and LAK lysis. Furthermore, preincubation of IFN-gamma treated breast cancer cells with F(ab')2 fragments of monoclonal antibodies to HLA class I and HLA class II molecules was unable to restore lysis. In contrast, several complete monoclonal antibodies including anti-HLA class I and HLA class II induced the lysis of target cells whether or not they had been treated by IFN gamma. The therapeutic use of monoclonal antibodies directed against antigens expressed on tumour cells (ADCC) in conjunction with interferon therapy should be discussed in lymphokine-based strategies for treatment of cancer patients. PMID- 2109998 TI - Endocrine disorders following treatment of childhood brain tumours. AB - We have studied the long-term endocrine effects of treatment on 144 children treated for brain tumours. All received cranial irradiation, 86 also received spinal irradiation and 34 chemotherapy. Almost all patients (140 of 144) had evidence of growth hormone insufficiency. Treatment with growth hormone was effective in maintaining normal growth but could not restore a deficit incurred by delay in instituting treatment. The effect of spinal irradiation on spinal growth was not corrected by growth hormone. As spinal growth makes the major contribution to the pubertal growth spurt and limb length the major contribution to childhood growth, treatment with GH will have maximal effect on leg length if instituted before the onset of puberty. Primary thyroid dysfunction was found in 11 of 47 children (23%) treated with craniospinal irradiation but in none treated with cranial irradiation alone. The incidence rose to 69% of 29 children treated with spinal irradiation and chemotherapy and to 50% of four children treated with cranial irradiation and chemotherapy. This effect of chemotherapy has not previously been reported and was detected by us through measurement of serum TSH concentration. Primary thyroid dysfunction requires treatment with thyroxine to prevent increasing the risk of secondary thyroid tumours. Seven of 20 girls (35%) treated with spinal irradiation had primary ovarian dysfunction as determined by raised gonadotrophin levels. Chemotherapy increased this, but not significantly. Three of 15 boys (20%) treated with chemotherapy had primary testicular dysfunction. Gonadotrophin deficiency occurred in seven boys. Four of 90 children had deficiency of cortisol secretion in response to hypoglycaemia. These results confirm the requirement for long-term follow-up of children treated for brain tumours from the endocrine point of view. Anticipation of hormone deficiencies and replacement treatment can improve the quality of life of survivors. PMID- 2109999 TI - Second non-germ cell malignancies after radiotherapy of testicular cancer with or without chemotherapy. AB - The incidence of a new primary non-germ cell malignancy was determined in 876 patients with testicular cancer treated at the Norwegian Radium Hospital from 1956 to 1977. Sixty-five patients developed a second cancer leading to a statistically significant increased relative risk (RR = 1.58), especially if extended radiotherapy had been given (RR = 4.13). The excess risks of developing lung cancer and malignant melanoma were 2.03 and 3.89, respectively. Increased RR for these two cancer types were seen both after extended radiotherapy and after radiotherapy combined with chemotherapy. Studies of the time between treatment and secondary lung cancer indicated that the development of the new lung cancer could be partly treatment related, whereas the raised incidence of malignant melanoma may be related to the frequent health checks performed in patients with testicular cancer. Patients who had received extended radiotherapy were also at an increased risk of developing cancer of the stomach and of the colon. Three cases of acute leukaemia were observed more than 5 years after treatment, all of them in patients who had received abdominal radiotherapy only. It is concluded that patients apparently cured of a testicular cancer have an increased risk of developing a new treatment related non-germ cell malignancy, in particular lung cancer. The application of the extended radiotherapy or the combination of radiotherapy and chemotherapy containing alkylating drugs should be avoided in order to reduce this excess risk. PMID- 2110000 TI - Effects of nucleotide- and aurodox-induced changes in elongation factor Tu conformation upon its interactions with aminoacyl transfer RNA. A fluorescence study. AB - The effects of GDP and of aurodox (N-methylkirromycin) on the affinity of elongation factor Tu (EF-Tu) for aminoacyl-tRNA (aa-tRNA) have been quantified spectroscopically by using Phe-tRNA(Phe)-Fl8, a functionally active analogue of Phe-tRNA(Phe) with a fluorescein dye convalently attached to the s4U-8 base. The association of EF-Tu.GDP with Phe-tRNA(Phe)-Fl8 resulted in an average increase of 33% in fluorescein emission intensity. This spectral change was used to monitor the extent of ternary complex formation as a function of EF-Tu.GDP concentration, and hence to obtain a dissociation constant, directly and at equilibrium, for the EF-Tu.GDP-containing ternary complex. The Kd for the Phe tRNA(Phe)-Fl8.EF-Tu.GDP complex was found to average 28.5 microM, more than 33,000-fold greater than the Kd of the Phe-tRNA(Phe)-Fl8.EF-Tu.GTP complex under the same conditions. In terms of free energy, the delta G degree for ternary complex formation at 6 degrees C was -11.5 kcal/mol with GTP and -5.8 kcal/mol with GDP. Thus, the hydrolysis of the ternary complex GTP results in a dramatic decrease in the affinity of EF-Tu for aa-tRNA, thereby facilitating the release of EF-Tu.GDP from the aa-tRNA on the ribosome. Aurodox (200 microM) decreased the Kd of the GDP complex by nearly 20-fold, to 1.46 microM, and increased the Kd of the GTP complex by at least 6-fold. The binding of aurodox to EF-Tu therefore both considerably strengthens EF-Tu.GDP affinity for aa-tRNA and also weakens EF Tu.GTP affinity for aa-tRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110002 TI - Determination of the regions of the clathrin molecule inducing membrane fusion. AB - Clathrin induces fusion of liposome membranes containing phosphatidylserine at acidic pH [Maezawa, S., Yoshimura, T., Hong, K., Duzgunes, N., & Papahadjopoulos, D. (1989) Biochemistry 28, 1422-1428]. The regions of the clathrin molecule inducing membrane fusion were determined by examining the fusion abilities of clathrin fragments obtained by limited proteolysis of clathrin cages with thermolysin. Membrane fusion was assessed by resonance energy transfer assay in terms of the dilution of fluorescent phospholipids in liposome membranes. Proteolysis of clathrin decreased the fusion rate and the amount of protein but did not affect the specific fusion rate (i.e., the fusion rate per unit of protein), indicating that clathrin fragments retain the ability to induce fusion. Of the two proteolytic fragments of the clathrin heavy chain, the terminal domain and the residual proximal part, which were separated by ultracentrifugation or gel chromatography, only the proximal part showed fusion activity. Light chains seemed to have no role in membrane fusion, since they are susceptible to proteolytic digestion. The terminal domain induced reversible liposome membrane aggregation, which was also induced by the residual proximal part of the heavy chain and the whole molecule of clathrin. These results suggest that the terminal domain and the proximal portion of clathrin have critical roles in the steps of close apposition and fusion of membranes, respectively. PMID- 2110001 TI - Threonine 1336 of the human insulin receptor is a major target for phosphorylation by protein kinase C. AB - The ability of tumor-promoting phorbol diesters to inhibit both insulin receptor tyrosine kinase activity and its intracellular signaling correlates with the phosphorylation of the insulin receptor beta subunit on serine and threonine residues. In the present studies, mouse 3T3 fibroblasts transfected with a human insulin receptor cDNA and expressing greater than one million of these receptors per cell were labeled with [32P]phosphate and treated with or without 100 nM 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA). Phosphorylated insulin receptors were immunoprecipitated and digested with trypsin. Alternatively, insulin receptors affinity purified from human term placenta were phosphorylated by protein kinase C prior to trypsin digestion of the 32P-labeled beta subunit. Analysis of the tryptic phosphopeptides from both the in vivo and in vitro labeled receptors by reversed-phase HPLC and two-dimensional thin-layer separation revealed that PMA and protein kinase C enhanced the phosphorylation of a peptide with identical chromatographic properties. Partial hydrolysis and radiosequence analysis of the phosphopeptide derived from insulin receptor phosphorylated by protein kinase C indicated that the phosphorylation of this tryptic peptide occurred specifically on a threonine, three amino acids from the amino terminus of the tryptic fragment. Comparison of these data with the known, deduced receptor sequence suggested that the receptor-derived tryptic phosphopeptide might be Ile-Leu-Thr(P)-Leu-Pro-Arg. Comigration of a phosphorylated synthetic peptide containing this sequence with the receptor derived phosphopeptide confirmed the identity of the tryptic fragment. The phosphorylation site corresponds to threonine 1336 in the human insulin receptor beta subunit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110003 TI - Purification and characterization of 6-pyruvoyl-tetrahydropterin synthase from Drosophila melanogaster. AB - The enzyme 6-pyruvoyl-tetrahydropterin synthase (PTP synthase), which catalyzes the conversion of 7,8-dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin, has been purified approx. 230-fold to apparent homogeneity from head extracts of Drosophila melanogaster. A partially purified 6-pyruvoyl tetrahydropterin reductase (PTP reductase) was also prepared and in its presence, along with Mg2+ and NADPH, the purified PTP synthase converted 7,8 dihydroneopterin triphosphate to metastable 6-lactoyltetrahydropterin, which was autoxidized to sepiapterin under aerobic conditions. Purified PTP synthase had a specific activity of 3792 units per mg protein and migrated as a single protein band on both nondenaturing polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purified active enzyme consisted of at least two identical subunits which had a molecular mass of 37.5 kDa on SDS-PAGE and NH2-Asx-Pro- as N-terminal amino acids. The native enzyme in crude extract was shown to be more complex, existing as higher multimeric forms. PMID- 2110004 TI - Anti-TNP antibody localization of the reactive lysine residues in myosin. AB - Myosin contains reactive lysine residues which are trinitrophenylated by 2,4,6 trinitrobenzene sulfonate much faster than the rest of the lysines. Here we find the location of these residues in the primary and spatial structure of myosin with the help of an anti-trinitrophenyl antibody. This antibody was raised against trinitrophenyl hemocyanin in rabbits. It reacted with trinitrophenylated myosin, and with some of the tryptic fragments of trinitrophenylated myosin. By analyzing the reaction with Western blots, it was found that the antibody preferentially reacts with the 27 kDa N-terminal fragment of the myosin head, and more weakly with the light meromyosin region of the myosin rod. The 27 kDa fragment contains the most reactive lysine residue, while the intermediate lysine residue is located in the light meromyosin region. The locations of the epitopes of the antibody were visualized on electron microscope images of rotary-shadowed trinitrophenylated myosin-antibody complexes. The distances of the epitopes to the head-rod junction of myosin were measured as 13 and 113 nm for the epitope on the head (reactive lysine residue) and for that on the rod (intermediary reactive lysine residue), respectively. PMID- 2110005 TI - Cat and monkey cortical columnar patterns modeled by bandpass-filtered 2D white noise. AB - A simple algorithm based on bandpass-filtering of white noise images provides good quality computer reconstruction of the cat and monkey ocular dominance and orientation column patterns. A small number of parameters control the frequency, orientation, "branchedness", and "regularity" of the column patterns. An oriented (anisotropic) bandpass filter followed by a threshold operation models the macaque ocular dominance column pattern and cat orientation column system. An unoriented (isotropic) bandpass filter models the cat ocular dominance column pattern and the macaque orientation column system. The resemblance of computer graphic simulations produced by this algorithm and histological pattern data, is strong. Since this algorithm is very fast, we have been able to extensively explore its parameters space in order to determine filter parameters which closely match the structure of the various cortical systems. In particular, we have applied spectral analysis to our recent computer reconstruction of the macaque ocular dominance column system, and the model produced by the present algorithm is in close agreement with this detailed data analysis. PMID- 2110006 TI - TSH response to TRH and family history of alcoholism. AB - The thyrotropin (TSH) response to intravenous thyrotropin-releasing hormone (TRH) was evaluated in 10 sons of alcoholic fathers (FHP group) and 10 matched controls (FHN group). No differences were observed between the two groups in basal TSH, peak TSH levels, on the incidence of TSH-blunting to TRH. Though there was a trend for a less intense TSH response over time after the TRH infusion, the difference between the family groups was not significant. These results are not consistent with some previous reports of an increased percentage of blunted TSH response to TRH for children of alcoholics. The clinical and research implications of these findings are discussed. PMID- 2110007 TI - Range of the influence of the carbohydrate moiety on the conformation of the poly(amino acid) backbone in glycosylated mucins. AB - The influence of glycosylation on the conformational properties of porcine submaxillary gland mucin has been investigated using rotational isomeric state theory. The specific objective was to determine the conditions under which the polypeptide has the relatively large mean square unperturbed radius of gyration mean value of s2(0), demanded by the measurements of Shogren et al., while retaining the overall architecture of a random coil. The mean square dimensions were monitored as the dimensionless characteristic ratio defined as C = mean value of s2(0)/npl2p, and the overall architecture was monitored by another dimensionless ratio mean value of r2(0)/mean value of s2(0), where mean value of r2(0) denotes the mean square unperturbed end-to-end distance. The computed values of C cannot reproduce the measured values if the conformational influence of glycosylation is restricted to each Ser or Thr, or if this influence extends only as far as their nearest neighbors. Values of C compatible with experiment can be obtained if the influence extends to next nearest neighbors. The behavior of the computed values of mean value of r2(0)/mean value of s2(0) permits an assignment of 7 +/- 1 as the likely upper limit to the number of consecutive amino acid residues that experience alterations in phi and psi if the sequence contains a glycosylated Ser or Thr. PMID- 2110008 TI - A unique binding cavity for divalent cations in the DNA-metal-chromomycin A3 complex. AB - Binding of chromomycin A3 (CRA) to calf thymus DNA was investigated in the presence of divalent cations using visible absorption and 1H-nmr spectroscopies. An apparent equilibrium binding constant (approximately 10(11) M-1) was obtained from metal competition experiments using EDTA to remove the metal cation from the DNA-M-CRA (M: metal) complex. The large binding constant of the drug to DNA enabled us to obtain essentially complete complexation of CRA to the short homogeneous d(ATGCAT)2 duplex using stoichiometric amounts of the metal cation. Large induced chemical shifts were observed in the 1H-nmr spectrum of the above complex using the paramagnetic Co2+ cation, indicating that the metal occupies a unique binding site. Since no induced 1H-nmr chemical shifts were observed for the drug-Co2+ mixture, it was concluded that no metal-drug complex is formed. In addition, it was found that bound CRA is negatively charged at physiological pH and binding to the DNA could be affected only by using metal cations whose ionic radius size (less than 0.85 A) and charge (2+) were simultaneously satisfied. Stringent metal cation selectivity for the DNA-M-CRA complex may be intimately connected with the antitumor selectivity of CRA, since different types of cells generally possess widely differing molar concentrations of metal cations. PMID- 2110009 TI - Localization of breakpoints by polymerase chain reactions in Burkitt's lymphoma with 8;14 translocations. AB - Translocations involving chromosomes 8 and 14 in Burkitt's lymphoma (BL) often involve the switch mu (Smu) region on chromosome 14, which contains multiple repeats. This has enabled us to use the polymerase chain reaction (PCR) to detect breakpoints that involve this region on chromosome 14 and the c-myc gene on chromosome 8. Using pairs of flanking primers, each pair including one annealing to repeat sequences within the switch region and one of three primers from the c myc region (first intron, 3', or 5' flanking sequence of the first exon of c myc), we have been able to amplify DNA fragments containing the corresponding breakpoint regions from chromosome 14 in both cell lines and biopsied tumor samples. The definitive demonstration of sequences from both chromosomes in these fragments permitted the confirmation of the presence of a translocation. Because of the sensitivity of PCR, we were able to localize breakpoints in samples containing as few as 1 neoplastic cell in 10(8) cells. PCR provides a valuable tool for the detection of 8;14 chromosomal translocations, which should prove to be of value in diagnosis and molecular epidemiologic studies, as well as providing a means of detecting minimal disease. PMID- 2110011 TI - Metabolism studies of the antischistosomal drug praziquantel using tandem mass spectrometry: distribution of parent drug and ten metabolites obtained from control and schistosome-infected mouse urine. AB - The collisionally activated dissociation spectrum of the antischistosomal drug praziquantel (PZQ) has many structure-specific fragmentations which permit identification of PZQ and seventeen of its hydroxylated metabolites in mouse urine. These fragmentations may also be used to quantify the metabolic pattern of PZQ. In the present study, a triple-quadrupole mass spectrometer system has been used to generate [M + H]+ ions for PZQ and its monohydroxy, dihydroxy and trihydroxy metabolites which yield daughter ions capable of quantifying PZQ and ten of these metabolites. The goal of these experiments was to evaluate the effect of this hepatic infection on drug metabolism. This was accomplished in two steps. First, the amount of unmetabolized, mono- and dihydroxylated PZQ was established from the [M + H]+ ions. Then the specific metabolites at each level of hydroxylation were determined from daughter ion spectra. The product of these two values produces the metabolite pattern. The reproducibility of these assays ranged from good, with a coefficient of variation of 3% for the most abundant metabolite, to poor (43%) for PZQ, which is only 1% of the total elimination pattern. The excretion of unchanged PZQ and two dihydroxylated metabolites was enhanced in animals bearing schistosomiasis compared to control mice, while a third dihydroxylated metabolite was depressed. PMID- 2110010 TI - Metabolism studies of the antischistosomal drug praziquantel using tandem mass spectrometry: qualitative identification of 17 hydroxylated metabolites from mouse urine. AB - Schistosomiasis is a parasitic liver infection which is known to affect many aspects of drug metabolism. Praziquantel (PZQ) is the drug of choice for treating this disease. PZQ is known to be highly metabolized, but the effect of the disease on its metabolism has not been investigated. Control mice and mice infected with Schistosoma mansoni were dosed with PZQ and their urines were examined for the presence of metabolites using a triple-quadrupole mass spectrometer (tandem mass spectrometer). The collisionally induced dissociation of PZQ was remarkable in its structurally significant fragments. From this we were able to identify 17 hydroxylated metabolites of PZQ from purified urine samples without further chemical separation, including three monohydroxylated, six dihydroxylated, and eight trihydroxylated metabolites. There were no qualitative differences in metabolite production between control and infected animals. PMID- 2110012 TI - 2-substituted indazolinones: orally active and selective 5-lipoxygenase inhibitors with anti-inflammatory activity. AB - 1. This paper describes the pharmacological profile of ICI207968, a novel, orally active and selective inhibitor of 5-lipoxygenase. 2. Inhibition of leukotriene B4 (LTB4) synthesis by 2-substituted indazolinones was not directly related to redox potential but was critically dependent on the nature of the N2 substituent. 2-(3 Pyridylmethyl)-indazolinone (ICI207968) combined selectivity and oral potency. 3. In several in vitro systems ICI207968 exhibited similar lipoxygenase inhibitory potency (IC50 values from 1.5 microM to 6.0 microM) and was approximately 300 times less potent against cyclo-oxygenase, as measured by inhibition of prostaglandin E2 (PGE2) synthesis. 4. ICI207968 also produced selective lipoxygenase inhibition following oral administration in the rat. ED50 values of 2.5, 10 and 25 mg kg-1 p.o. for inhibition of LTB4 release from A23187-stimulated blood were obtained 1, 3 and 5 h after dosing. The compound did not inhibit PGE2 synthesis at oral doses up to 300 mg kg-1. 5. Co-administration of ICI207968 with arachidonic acid, into rabbit dermis, potently inhibited both plasma extravasation and polymorphonuclear leucocyte (PMNL) infiltration induced by this inflammatory fatty acid. The anti-inflammatory potency of a number of intradermally administered indazolinones, with similar redox potentials, was related to their inhibitory potency against leukotriene generation in blood. Oral administration of ICI207968 (100 mg kg-1) in the rabbit inhibited ex vivo leukotriene generation in blood and arachidonic acid-induced skin inflammation. 6. These data demonstrate that ICI207968 is an orally active and selective inhibitor of 5-lipoxygenase which has anti-inflammatory properties. IC1207968 will be a valuable agent for clarifying the biological roles of leukotrienes and the therapeutic potential of 5-lipoxygenase inhibitors. PMID- 2110013 TI - L-662,583 is a topically effective ocular hypotensive carbonic anhydrase inhibitor in experimental animals. AB - 1. L-662,583 was a potent inhibitor in vitro of purified, human erythrocyte carbonic anhydrase II, possessing an IC50 of 0.7 nM. The IC50 values for MK-927, acetazolamide and methazolamide were 13.0 nM, 10.8 nM and 21.2 nM, respectively. 2. A 1 h pretreatment with one 50 microliters drop of a 0.1% solution of L 662,583 blocked carbonic anhydrase activity in a homogenate of the iris + ciliary body of albino rabbits by 63%. Similar treatment with 0.1% suspensions of acetazolamide and methazolamide elicited inhibitions of 30% and 20%, respectively. This ex vivo model indirectly assesses the ability of an agent to enter the rabbit eye. 3. Concentrations of L-662,583 in the cornea, aqueous humour and iris + ciliary body of albino rabbits were determined by h.p.l.c. at predetermined times after the instillation (one drop of 50 microliters) of a 2% solution of L-662,583. Peak levels for cornea (47.4 micrograms g-1), aqueous humour (4.51 micrograms ml-1) and iris + ciliary body (9.61 micrograms g-1) occurred at 0.5, 2 and 1 h after instillation, respectively. 4. The experimentally elevated intraocular pressure of the right eye of rabbits, induced by prior intraocular injection of alpha-chymotrypsin, was maximally decreased by 4.5 mmHg, 6.2 mmHg and 9.8 mmHg after the instillation (one drop of 50 microliters) of 0.01%, 0.1% and 0.5% solutions of L-662,583, respectively. All three concentrations lowered intraocular pressure at all time points from 1 h up to and including 5 h, the last recorded time point. The unilateral instillation of L-662,583 (0.5%) into the contralateral, left eye failed to lower the elevated intraocular pressure of the untreated, right eye. This finding indicates that the site of action of topically applied L-662,583 in this paradigm is local. The ocular normotensive, albino rabbit was much less susceptible than the ocular hypertensive rabbit to the intraocular pressure lowering effect of topically applied L-662,583, with a 2% solution maximally decreasing intraocular pressure by 2.3 mmHg. 5. Unilateral ocular hypertension was elicited in the right eye of sedated, cynomolgus monkeys by argon laser-induced photocoagulation of the trabecular meshwork. The instillation (one drop of 50 microL) of L-662, 583 (2%) significantly lowered the elevated intraocular pressure of the right eye at all time points from 1 h up to and including 5 h. The maximum decline was 8.3 mmHg at 3 h and this represented a reduction of 23% from the corresponding baseline value of 36.8 mmHg. The intraocular pressure of the hypertensive, right eye was maximally decreased by 4.1 mmHg and 4.8 mmHg after the instillation of 0.5% and 1% solutions of L-662,583, respectively. Like the rabbit, the normotensive eye of cynomolgus monkeys was more resistant than the hypertensive eye to the ocular hypotensive action of L-662, 583, as indicated by the inability of 0.5% and 1% solutions of the agent to lower intraocular pressure. L-662,583 (2%) maximally reduced the intraocular pressure of normotensive monkey eyes by 2.4 mmHg at 2 h. 6. L-662,583 is structurally different from MK-927, a carbonic anhydrase inhibitor that lowers the intraocular pressure of glaucoma patients following the instillation of a 2% solution. These preclinical observations indicate that L 662,583, like MK-927, is a water-soluble carbonic anhydrase inhibitor which, on topical administration, lowers intraocular pressure by virtue of an action confined to within the eye. PMID- 2110014 TI - Protective effect of beraprost sodium, a new chemically stable prostacyclin analogue, against the deterioration of baroreceptor reflex following transient global cerebral ischaemia in dogs. AB - 1. A possible cerebroprotective effect of a chemically stable prostacyclin analogue, beraprost sodium, was investigated in a canine model of cerebral ischaemia. Cerebral ischaemia was produced by the combined occlusions of the left subclavian and the brachiocephalic arteries with preceding ligations of the intercostal arteries. 2. The decrease in baroreceptor reflex sensitivity (BRS), measured by phenylephrine-induced reflex bradycardia, following 5 min ischaemia was used to assess the cerebroprotective effect. 3. Beraprost (1 microgram kg-1 min-1 i.v., infused for 15 min just before ischaemia) completely prevented the decrease in BRS. Although the lower dose of beraprost (0.1 microgram kg-1 min-1 i.v.) failed to show such a protective effect, its inhibitory effect on ADP induced platelet aggregation was as potent as that of the higher dose. 4. The extent of decrease in BRS was inversely correlated with the extent of the residual blood flow in the medulla oblongata during ischaemia. Since beraprost did not affect the extent of the residual blood flow during ischaemia, its cerebroprotective effect could not be ascribed to the reduction of the degree of ischaemia by increasing collateral blood flow to the brain. 5. Post-ischaemic reduction of the regional blood flow in the medulla and the cerebral cortex was completely prevented by the higher dose of beraprost. 6. The present study suggests that the cerebroprotective effect of beraprost may be independent of its anti-aggregatory and vasodilator effects. It is possible that the protection may be due to a prostacyclin-like cytoprotective effect through membrane stabilization. PMID- 2110015 TI - Mediation of bradykinin-induced contraction in canine veins via thromboxane/prostaglandin endoperoxide receptor activation. AB - 1. Canine jugular and femoral veins were studied to determine the possible importance of thromboxane (TXA2) and prostaglandin endoperoxides (prostaglandin H2, PGH2) in mediating bradykinin(BK)-induced contraction. 2. Isolated vein rings incubated in modified Krebs solution contracted to TXA2/PGH2 analogs SQ26655 and U44069 with potency of contraction exceeding that for BK. The potency ranking for both veins was SQ26655 greater than U44069 greater than BK greater than PGF2 alpha greater than TXB2 much greater than PGD2. 3. The cyclo-oxygenase inhibitors indomethacin (3 x 10(-7) M) and flufenamic acid (10(-5) M) reduced BK contractions without affecting those induced by noradrenaline (NA). 4. TXA2/PGH2 receptor antagonists SQ29548 (10(-8) M) and BM13177 (10(-6) M) strongly inhibited BK-induced tension. The action of antagonists was reversible with negligible influence on NA-elicited contraction. Selective removal of endothelium had no effect on BK-induced contraction or the action of the antagonists. 5. The thromboxane synthase inhibitors dazoxiben (10(-4) M) and CGS 12970 (10(-5) M) had no significant inhibitory effect on BK-induced tension. 6. These results suggest that in canine jugular and femoral vein, the action of BK is largely dependent upon stimulation of the cyclo-oxygenase pathway to produce PGH2 and possibly TXA2, which can activate a smooth muscle TXA2/PGH2 receptor to elicit vasoconstriction. PMID- 2110016 TI - Relationships between tumour necrosis factor, eicosanoids and platelet-activating factor as mediators of endotoxin-induced shock in mice. AB - 1. The toxicity of intravenous recombinant human tumour necrosis factor (rhTNF), a TNF fragment (TNF114-130), endotoxin and combinations of rhTNF or TNF114-130 were tested in mice. Neither rhTNF nor TNF114-130 was lethal alone, but when combined with a non-lethal dose of endotoxin, rhTNF provoked dose-dependent mortality, as did higher doses of endotoxin alone. 2. Both the toxicity and the vasopermeability changes induced by endotoxin alone were blocked by the platelet activating factor (PAF) antagonist BN52021, indomethacin or the dual cyclo oxygenase/lipoxygenase inhibitor BW755C. 3. The lethality of the combined low dose endotoxin/rhTNF challenge was unaffected by pretreatment with BN52021, indomethacin or BW755C, or by treatment at 6 h intervals with BN52021 or BW755C. 4. The results of these studies suggest that TNF, a putative, early mediator of septic or endotoxin shock, cannot by itself mimic all of the effects of bacterial endotoxin in the model used in this study. Apparently, TNF works synergistically with other mediators whose release is stimulated by endotoxin. 5. The results also suggest that the mechanism of shock production by the rhTNF/endotoxin combination in mice is not dependent on the early stimulation of eicosanoid or PAF synthesis by rhTNF. PMID- 2110017 TI - Effects of B-HT 920 on nigrostriatal and mesolimbic dopamine systems in normosensitive and supersensitive rats. AB - 1. B-HT 920, a D2 dopamine receptor agonist, was tested for its ability to exert presynaptic actions in normosensitive rats, and for possible postsynaptic actions in rats made 'supersensitive' to apomorphine. 2. In normosensitive rats, B-HT 920 (0.01-0.3 mg kg-1, i.p.) increased dopamine concentrations and lowered metabolite levels to a similar extent in all four terminal regions examined (medial prefrontal cortex, olfactory tubercle, nucleus accumbens, caudate-putamen). Analogous effects were seen for 5-hydroxytryptamine and its metabolite 5 hydroxyindoleacetic acid. 3. Rats which received bilateral 6-hydroxydopamine (6 OHDA) infusions into the caudate-putamen showed signs of postsynaptic dopamine receptor activation (stereotyped behaviour) in response to B-HT 920 (0.1 and 1.0 mg kg-1, i.p.) and to apomorphine (0.2 mg kg-1, s.c.). Similarly, B-HT 920 (0.1 mg kg-1) induced contralateral circling in rats that had received unilateral 6 OHDA infusions into the medial forebrain bundle; the rate of circling increased gradually over several weeks. 4. In contrast, bilateral 6-OHDA infusions into the nucleus accumbens resulted in a supersensitive (locomotor stimulant) response to a low dose of apomorphine (0.1 mg kg-1, s.c.), but not to B-HT 920 (0.01 and 0.1 mg kg-1). 5. In intact rats, withdrawal of chronic haloperidol treatment induced behavioural supersensitivity to apomorphine but not to B-HT 920. PMID- 2110018 TI - Release of a neutrophil-derived vasoconstrictor agent which augments platelet induced contractions of blood vessels in vitro. AB - 1. The effects of neutrophil-derived products on vascular tone in vitro were examined by adding purified rabbit neutrophils to siliconized organ baths containing rings of rabbit thoracic aorta. 2. Neutrophil-derived products induced a concentration-dependent contraction of the blood vessels generating 3.9 +/- 0.2 g of tension at a cell concentration of 2 X 10(6) ml-1. This contractile response was not dependent on an intact endothelium and was not ameliorated by treatment of the neutrophils with inhibitors of lipoxygenase or cyclo-oxygenase enzymes, by free radical scavengers or by the use of end organ antagonists to angiotensin II, desArg9-bradykinin, histamine, catecholamines or acetylcholine. 3. Neutrophils stimulated with phorbol myristate acetate, formyl methionyl-leucyl-phenylalanine or calcium ionophore A23187 released a contractile factor into the supernatant which produced qualitatively similar contractions compared to those elicited by incubation with intact unstimulated neutrophils. 4. Ten to twenty times more platelets were required to evoke equivalent contractions to those observed with neutrophils. However, neutrophil supernates significantly augmented platelet mediated contractions (P less than 0.001). 5. Contractions elicited by neutrophils and supernates derived from activated neutrophils were partially antagonized by 5-hydroxytryptamine (5-HT) receptor antagonists, methysergide and ketanserin. However, the inhibition of exogenous 5-HT-induced contractions on rabbit aorta and rat stomach strips by both antagonists was greater than the inhibition of contractions produced by neutrophils and neutrophil-derived supernates. 6. Extraction of the biologically active material from supernatants of activated neutrophils into acetone, but not chloroform-methanol or ethyl acetate, suggests the contractile factor may be a protein/peptide. Partial purification on a Sephadex G100 column yields a contractile factor with a molecular weight of less than 4,000 daltons. 7. This factor may augment vascular tone, either directly or by interactions with platelets, in pathophysiological states associated with neutrophil activation and accumulation. PMID- 2110020 TI - [The organization of the cortex in ciliates: an example of inheriting an acquired trait]. AB - Observations and experiments concerning morphology, morphogenesis and regeneration of ciliates impose the conclusion that the cortex plays a determining role in the arrangement of kinetics and that its organization is not commanded by the genome but behaves as an acquired hereditary character. PMID- 2110021 TI - Laryngeal cancer: new directions in treatment. PMID- 2110019 TI - Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat. AB - 1. The interactions between nitric oxide (NO), prostacyclin and sensory neuropeptides in the maintenance of gastric mucosal integrity have been investigated in the anaesthetized rat. 2. Administration of either NG-monomethyl L-arginine (L-NMMA) to inhibit endothelium-derived NO formation, indomethacin to inhibit prostanoid biosynthesis or chronic capsaicin pretreatment to deplete sensory neuropeptides, did not induce acute mucosal injury. 3. In capsaicin pretreated rats, however, L-NMMA (12.5-100 mg kg-1 i.v.) dose-dependently induced acute mucosal damage, characterized as vasocongestion and haemorrhagic necrosis. The enatiomer D-NMMA (100 mg kg-1 i.v.) did not induce any detectable mucosal damage. 4. This mucosal injury induced by L-NMMA was inhibited by concurrent administration of L-arginine (300 mg kg-1 i.v.). 5. In indomethacin (5 mg kg-1 i.v.)-pretreated rats, L-NMMA also induced mucosal damage. Furthermore, following indomethacin administration in capsaicin-pretreated rats, L-NMMA induced widespread, severe haemorrhagic necrotic damage. 6. These findings suggest a role for endogenous NO formed from L-arginine, acting in concert with prostacyclin and sensory neuropeptides, in the modulation of gastric mucosal integrity. PMID- 2110022 TI - The role of radiation therapy in laryngeal cancer. PMID- 2110023 TI - "Psychic surgery". AB - After study of the literature and other available information, the American Cancer Society has found no evidence that "psychic surgery" results in objective benefit in the treatment of any medical condition. Lacking such evidence, the American Cancer Society strongly urges individuals who are ill not to seek treatment by psychic surgery. The following is a review and summary of material on "psychic surgery" in the American Cancer Society files as of May 31, 1989. Reference to that material by the Society does not imply agreement with its contents. PMID- 2110024 TI - Cancer and the poor. PMID- 2110025 TI - Chemotherapy-related nausea and vomiting. PMID- 2110026 TI - Prostate cancer screening. PMID- 2110027 TI - Clinical evaluation of glass ionomer-silver cermet restorations in primary molars: one year results. AB - Using the half mouth technique, 33 silver amalgam (Dispersalloy) and 40 glass ionomer (Ketec silver) restorations were placed in the primary molars of children aged five to seven years. After one year, 73 restorations were evaluated. The amalgam restorations rated 90-100 per cent alpha for anatomic form and margins with no recurrent caries or fractures. The glass ionomer restorations rated 35 to 55 per cent alpha for anatomic form and margins with 40 per cent being replaced due to fracture of the material. Within the guidelines of this study, glass ionomer silver cermet was not a suitable material for the restoration of interproximal cavities in primary molars. PMID- 2110028 TI - Infant and preschool immunization delivery in Alberta and Ontario: a partial cost minimization analysis. AB - This paper is a partial cost-minimization analysis of preschool immunization delivery in Alberta and Ontario. Public health nurses deliver such immunization in Alberta while in Ontario it is usually provided by private physicians. In constant 1986 dollars, labour costs were 2.9 times higher in Ontario than in Alberta. Alberta and Ontario achieved equal success in preventing diphtheria, tetanus and poliomyelitis in the target population of zero to four years of age. Ontario's pertussis rates were higher than Alberta's from 1980 to 1986 inclusive (p less than 0.01). Rubella rates were higher in Alberta from 1980 to 1986 inclusive (p less than 0.05) but the congenital rubella rates for the same period were not. During 1980, Ontario's measles rate was higher (p less than 0.01) while for 1982 and 1986, Alberta's measles rates were higher. In 1986, Alberta's mumps rate was higher than Ontario's (p less than 0.01). The findings argue in favour of the less costly public health nurse approach to immunization delivery. A more definitive conclusion could have been reached had the provinces maintained more detailed age-specific disease incidence data. PMID- 2110029 TI - A murine plasmacytoma with a variant (15;16)(D2/3;B1) translocation that involves the c-myc and lambda light chain gene-carrying chromosomes. AB - A murine plasmacytoma (MPC) with a reciprocal translocation between chromosomes 15 and 16 with breakpoints in 15D2/3 and 16B1 is reported. The breakpoint on chromosome 15 is identical to the breakpoint in the MPC-associated typical (12;15) and kappa variant (6;15) translocation. Therefore it probably involves the c-myc gene as well. Unlike the Burkitt lymphoma (BL) system, a lambda/myc variant translocation has not been described in the MPC system. Chromosome 16 is known to carry the lambda gene. Therefore, the 15;16 translocation probably represents the "missing" lambda/myc variant in MPC, suggesting that the lambda gene is localized at 16B1. PMID- 2110030 TI - [Urinary excretion of phenol in Crohn disease during total parenteral nutrition]. AB - Urinary phenol is a product of dietary tyrosine metabolism generated in the gut by bacteria. In our previous study we found in 42 patients with Crohn's disease a significantly higher level of urinary phenol in terminal ileitis and ileal resection when compared with Crohn's segmental colitis. Urinary phenol is believed to be extensively influenced by diet. For this purpose our present paper investigated urinary phenol in Crohn's disease before and after two weeks of total parenteral nutrition. Spectrophotometric analysis of urinary phenol was carried out in 10 patients (7 males, 3 females). They ranged from 24 to 40 (average 34.9) years of age. The patients received on an average 1.45 g of amino acids/kg/day (no tyrosine; 0.022 g of L-phenyl-alanine/kg/day), 25-30 kcal/kg/day (105-125 kJ/kg/day) in non-protein sources of energy, and fat-emulsions (80 g/day) twice a week. There was a significant decrease in the urinary phenol after two weeks of total parenteral nutrition (median 79.5, interquartile range 41.5 to 288.5 mumols/24 hours vs. median 37.5, interquartile range 0-93.5 mumols/24 hours), p = 0.032 using the paired t-test. In two patients with severe involvement of the gut, urinary phenol, though decreased, remained at higher levels (above 300 mumols/24 hours). A significant decrease of the urinary phenol can be explained in particular by exclusion of dietary proteins, although clinical and nutritional improvement was observed, too. However, persisting higher levels of urinary phenol in some patients with serious involvement of the gut may reflect the severity of Crohn's disease. PMID- 2110032 TI - Penicillinase-producing Neisseria gonorrhoeae infections in Quebec: an assessment of the situation to the end of 1988. PMID- 2110031 TI - TGF-beta 1 inhibition of transin/stromelysin gene expression is mediated through a Fos binding sequence. AB - Transforming growth factor beta 1 (TGF-beta 1) inhibits the growth factor and oncogene induction of transin/stromelysin, a secreted matrix-degrading metalloprotease. We demonstrate that a 10 bp element in the transin promoter is required for the TGF-beta 1 inhibitory effects and that this sequence is conserved in the promoter regions of several other TGF-beta 1-inhibited genes. The TGF-beta 1 inhibitory element (TIE) specifically binds a nuclear protein complex from TGF-beta 1-stimulated rat fibroblasts. Interestingly, this complex contained the c-fos proto-oncogene product, Fos, and induction of Fos expression was required for the inhibitory effect of TGF-beta 1 on transin gene expression. These results suggest that TGF-beta 1 inhibition of gene expression is mediated by the binding of a Fos-containing protein complex to the TIE promoter sequences. PMID- 2110034 TI - Relation of pulmonary vein to mitral flow velocities by transesophageal Doppler echocardiography. Effect of different loading conditions. AB - It has previously been demonstrated that predictable changes occur in mitral flow velocities under different loading conditions. The purpose of this study was to relate changes in pulmonary venous and mitral flow velocities during different loading conditions as assessed by transesophageal echocardiography in the operating room. Nineteen patients had measurements of hemodynamics, that is, mitral and pulmonary vein flow velocities during the control situation, a decrease in preload by administration of nitroglycerin, an increase in preload by administration of fluids, and an increase in afterload by infusion of phenylephrine. There was a direct correlation between the changes in the mitral E velocity and the early peak diastolic velocity in the pulmonary vein curves (r = 0.61) as well as a direct correlation between the deceleration time of the mitral and pulmonary venous flow velocities in early diastole (r = 0.84). This indicates that diastolic flow velocity in the pulmonary vein is determined by the same factors that influence the mitral flow velocity curves. A decrease in preload caused a significant reduction in the initial E velocity and prolongation of deceleration time, and an increase in preload caused an increase in E velocity and shortening of deceleration time. An increase in afterload produced a variable effect on the initial E velocity and deceleration time and was dependent on the left ventricular filling pressure. The change in systolic forward flow velocity in the pulmonary vein was directly proportional to the change in cardiac output (r = 0.60). The pulmonary capillary wedge pressure correlated best with the flow velocity reversal in the pulmonary vein at atrial contraction (r = 0.81). Use of pulmonary vein velocities in conjunction with mitral flow velocities can help in understanding left ventricular filling. PMID- 2110033 TI - Comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator. Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II-A trial. AB - To assess the value and timing of percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction (AMI), 586 patients in the Thrombolysis in Myocardial Infarction Study Phase II-A were randomized among three treatment strategies, one using immediate coronary arteriography followed by PTCA if appropriate (immediate invasive strategy group, n = 195), a second that deferred angiography and PTCA for 18-48 hours (delayed invasive strategy group, n = 194), and a third, more conservative, approach in which PTCA was used only if ischemia occurred spontaneously or at the time of predischarge exercise testing (conservative strategy group, n = 197). Predischarge contrast left ventricular ejection fraction, the primary study end point, was similar among the patients in all three treatment groups and averaged 49.3%. The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001). Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01). Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001). At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%), although the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001). Thus, because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy. PMID- 2110035 TI - Body fat distribution and male/female differences in lipids and lipoproteins. AB - The role of body fat distribution, as assessed by the ratio of waist-to-hip circumferences (WHR), in statistically explaining differences in levels of lipoproteins between men and women was studied using data collected in 1985-1986 from employed adults (mean age, 40 years). As compared with the 415 women, the 709 men had higher mean levels of triglycerides (+38 mg/dl) and apolipoprotein B (+11 mg/dl) as well as lower mean levels of high density lipoprotein (HDL) cholesterol (-15 mg/dl) and apolipoprotein A-I (-19 mg/dl). Additionally, men were more overweight, consumed more alcohol, and exercised more frequently than women but were less likely to smoke cigarettes. Controlling for these characteristics, however, did not alter the differences in lipoprotein levels between men and women. In contrast, adjustment for WHR (which was greater among men) reduced the sex differences in levels of apolipoprotein B (by 98%), triglycerides (by 94%), HDL cholesterol (by 33%), and apolipoprotein A-I (by 21%). Similar results were obtained using analysis of covariance, stratification, or matching; at comparable levels of WHR, differences in lipid and lipoprotein levels between men and women were greatly reduced. Although these results are based on cross-sectional analyses of employed adults and need to be replicated in other populations, the findings emphasize the relative importance of body fat distribution. Whereas generalized obesity and body fat distribution are associated with lipid levels, fat distribution (or a characteristic influencing fat patterning) can be an important determinant of sex differences in levels of triglycerides, HDL cholesterol, and apolipoproteins B and A-I. PMID- 2110036 TI - Endothelium-dependent vascular relaxation is abnormal in the coronary microcirculation of atherosclerotic primates. AB - Atherosclerosis impairs endothelium-dependent relaxation of large conduit arteries. Because coronary resistance vessels are spared from the development of overt atherosclerosis, endothelium-dependent responses were examined in these vascular segments. Malaysian cynomolgus monkeys (n = 6) were made atherosclerotic by being fed a 0.7% cholesterol diet for 18 months. Control monkeys (n = 6) were fed a standard diet. Coronary microvessels (122-220 microns) were studied in a pressurized (20 mm Hg), no-flow state using a video-imaging apparatus. Relaxations of microvessels, preconstricted with the thromboxane analogue U46619, were determined in response to acetylcholine, bradykinin, the calcium ionophore A23187, adenosine, and sodium nitroprusside. Microvascular relaxations to bradykinin and A23187 were reduced in atherosclerotic monkeys compared with controls, whereas acetylcholine produced additional contraction in atherosclerotic monkeys. Responses of preconstricted microvessels to adenosine and sodium nitroprusside were identical in atherosclerotic and control animals. Indomethacin did not alter responses in control or atherosclerotic animals. Histologic examination revealed neither intimal thickening nor plaque formation in microvessels of this size class despite marked changes in conduit arteries. Electron microscopy showed minor alterations of endothelial cell morphology in microvessels of atherosclerotic animals. In conclusion, long-term hypercholesterolemia markedly impairs endothelium-dependent vascular relaxation in the coronary microcirculation where overt atherosclerosis does not develop. These changes in endothelial cell function may significantly alter regulation of myocardial perfusion by neurohumoral stimuli. PMID- 2110037 TI - Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium. AB - Extraction and clearance kinetics of [1-11C]acetate were examined in 65 experiments in 30 open-chest dogs. Twenty-nine studies were performed at control, 13 during ischemia, eight after reperfusion, 13 during dipyridamole-induced hyperemia, and two during alteration of cardiac workload. [1-11C]Acetate was injected directly into the left anterior descending coronary artery, and myocardial tissue-time activity curves were recorded with a gamma probe. The single-pass extraction fraction averaged 64.2 +/- 9.7% in control, 65.3 +/- 9.1% in ischemia, 70.0 +/- 4.4% in reperfusion, and 46.5 +/- 7.4% in dipyridamole induced hyperemia groups. 11C clearance was biexponential in all cases. The rate constant k1 for the first rapid clearance phase correlated closely with myocardial oxygen consumption (r = 0.94) in control, ischemia, reperfusion, and dipyridamole-induced hyperemia groups. Monoexponential fitting of only the first linear part of the clearance curve yielded the rate constant kmono, which also correlated with myocardial oxygen consumption (r = 0.96). Arterial lactate concentrations and the amount of free fatty acid oxygen equivalents consumed by the myocardium were shown to have a small but statistically significant impact on the relation between [1-11C]acetate clearance rate constants and myocardial oxygen consumption. The fraction of 14CO2 activity contributing to overall 14C activity leaving the myocardium after simultaneous injection of [1-14C]acetate (n = 24) was relatively high in all cases (97.4 +/- 2.5% in control, 89 +/- 2.6% in ischemia, 94.1 +/- 3.5% in reperfusion, and greater than 99% in dipyridamole groups), indicating that externally measured 11C clearance corresponds to CO2 production and thus to tricarboxylic acid cycle activity. In conclusion, the results validate the use of [1-11C]acetate as a tracer of oxidative myocardial metabolism for use with positron emission tomography. PMID- 2110038 TI - Do we need to intervene after thrombolysis in acute myocardial infarction? PMID- 2110039 TI - Trophic control of the ornithine decarboxylase/polyamine system in neonatal rat brain regions: lesions caused by 6-hydroxydopamine produce effects selective for cerebellum. AB - Norepinephrine has been hypothesized as a trophic factor influencing postnatal development of the cerebellum. In the current study, neonatal rats were given 6 hydroxydopamine (6-OHDA) to destroy noradrenergic projections and the effects on the ornithine decarboxylase (ODC)/polyamine system were evaluated; ODC initiates the synthesis of polyamines, which are known to control cellular development in the cerebellum, and neonatal ODC activity is regulated in part by beta 2 adrenergic receptors. Intracisternal administration of 6-OHDA resulted in complete and permanent depletion of cerebellar norepinephrine and a deficit in ODC, polyamine levels and cerebellar growth. Subcutaneous administration of 6 OHDA, which caused only a small initial reduction in cerebellar norepinephrine, did not affect ODC and had only minor effects on tissue growth. Indeed, levels of the polyamines tended to be elevated after subcutaneous 6-OHDA, associated with postweaning elevations in norepinephrine, results which are probably indicative of axonal regeneration. In contrast to the effects of 6-OHDA on cerebellar development, neither the intracisternal nor subcutaneous drug treatment had any effect on cerebral cortical polyamines or growth, although the intracisternal treatment did impair ODC activity early in development. These data suggest that postnatal noradrenergic input, acting through the ODC/polyamine pathway, plays a selective role in cerebellar development. PMID- 2110040 TI - Localized calcium influx orients axon formation in embryonic hippocampal pyramidal neurons. AB - A fundamental property of neurons is their polarization into distinct axonal and dendritic compartments which have characteristic structural and functional properties. The mechanisms regulating the formation of neuronal polarity are unknown. We used cultured embryonic rat hippocampal pyramidal neurons to test the hypothesis that a localized calcium influx can orient axon formation, and thereby direct the establishment of neuronal polarity. Transection of an initial axon, or focal application of A23187 or K+ to the initial axon, caused a new axon to form at a site distant from the initial axon. Fura-2 measurements of intracellular calcium revealed a localized calcium influx at the site of axon transection or focal application of A23187 or K+, and a calcium gradient spreading into the soma. New axon formation was inhibited when axons were transected in medium lacking calcium or containing calcium-elevating agents (conditions which prevented the formation of a calcium gradient). When calcium ionophore A23187 was applied focally to neurons which had not yet established an axon, the axon always formed at a site distant from the site of ionophore application; bath exposure to A23187 prevented axon formation. Taken together, these data demonstrate that a localized influx of calcium can suppress axon formation at the site of influx, and can thereby influence where the axon forms. These data suggest that gradients of intracellular calcium may be involved in orienting neuronal polarity. PMID- 2110041 TI - The effect of regional differences in noradrenergic neuron growth patterns on juvenile kindling. AB - Kindling can be altered by a variety of lesions designed to deplete norepinephrine (NE). However, the effect of the regional alteration in NE concentration on seizure susceptibility has not been studied. Two different concentrations of 6-hydroxydopamine (6-OHDA) were administered to one-day-old rat pups. At age 18 days, rat with significant rostral brain NE loss, due to high dose 6-OHDA, had a faster rate of electrical kindling in the entorhinal cortex than controls. In contrast rats receiving low dose 6-OHDA which resulted in comparable forebrain NE depletion but with a dramatic hindbrain noradrenergic overgrowth showed no enhancement of kindling. These results suggest that in the immature rat the proconvulsant effect of forebrain NE depletion can be overridden by an augmentation of hindbrain NE growth patterns. PMID- 2110042 TI - Postnatal development of striatal dopamine function. II. Effects of neonatal 6 hydroxydopamine treatments on D1 and D2 receptors, adenylate cyclase activity and presynaptic dopamine function. AB - To evaluate the influence of patch and matrix ingrowth of DA terminals upon striatal DA (dopamine) receptor function, we performed bilateral intrastriatal (i.s.) or single intracisternal (i.c.) injections of 6-hydroxydopamine (6-OHDA) into rat pups at various postnatal ages and determined D1 and D2 receptor binding, adenylate cyclase activities and markers for presynaptic DA terminal density and turnover as the animals matured. All injection schedules yielded: (a) variable and partial loss of DA, (b) increased DA turnover, (c) small (15-40%) increases in D1 receptor number but no change in affinity for antagonist ([3H]SCH 23390), (d) 2-3-fold increases in affinity of D1 receptors for agonist (SKF 38393) with preserved regulation of agonist affinity by guanine nucleotide, (e) no significant changes in DA-, guanine-nucleotide-, manganese- and forskolin stimulated AC (adenylate cyclase) activity. D2 receptor binding was evaluated between 1 and 7 weeks of age in animals with i.s. treatment and 7 and 10 weeks of age in animals with i.c. treatment and was reduced by 40-50% with both treatment regimens. [3H]mazindol binding, a marker for presynaptic terminal DA transport sites, was reduced 30-40% by multiple i.s. or i.c. treatment regimens. In animals treated with one i.s. injection, [3H]mazindol binding was reduced 70% at 1 week of age, equal to control by 2 weeks and 14-46% greater than control between 3 and 7 weeks. We conclude that striatal D1 receptor sites maintain their density and second messenger function independently of postsynaptic DA terminal ingrowth, whereas the development of D2 receptor sites is sensitive to disruptions of DA terminal ingrowth. PMID- 2110043 TI - Selective urinary screening for mucopolysaccharidoses. AB - Two methods for analysis of urinary glycosaminoglycans (GAGs) have been modified and improved for efficient screening of mucopolysaccharidoses. Urinary excretion of GAGs was estimated by spectrophometric measurement of alcian blue complex formation and was used in conjunction with qualitative analysis by thin layer chromatography. After normal variation in GAG excretion was established using 120 urine samples, these screening methods were applied to a total of 2057 urine samples over 4 years. Six patients with abnormal urinary GAG excretion had a mean of 50.5 +/- 20.6 mg GAG/mmol creatinine compared to 3.4 +/- 2.9 for age-matched controls. Qualitative analysis by thin layer chromatography using alternating solvent systems identified the GAGs excreted in excess and facilitated selection of specific enzyme assays for final confirmation. Six cases were diagnosed prospectively and demonstrate these quantitative and qualitative methods to be economical, efficient, and suitable for clinical use. PMID- 2110044 TI - Superovulation induction in women suppresses luteinizing hormone secretion at the pituitary level. AB - In superovulated women the pituitary response to GnRH is markedly attenuated by an unspecified ovarian factor(s). To examine the site of attenuation, the response of the pituitary to GnRH was investigated in five normally ovulating women during the late follicular phase of 3 cycles, i.e. a spontaneous (control) cycle, a cycle treated with 'pure' FSH, and a cycle treated with a combination of 'pure' FSH and pulsatile GnRH, via a pump (15 micrograms/pulse). The oestradiol levels (mean +/- SEM) at the time of the GnRH challenge were respectively 646 +/- 35, 1692 +/- 282 and 5976 +/- 1129 pmol/l. The size of the leading follicle was similar in all groups. Serum LH levels during treatment with FSH decreased significantly, while during treatment with FSH plus GnRH they increased initially and then decreased progressively. The response of pituitary LH to GnRH was significantly attenuated during treatment with FSH and FSH plus GnRH, as compared to the spontaneous cycles, but was not abolished. The attenuation was significantly greater in the FSH plus GnRH cycles (94%) than in the FSH cycles (59%). We conclude that in superovulated cycles, the attenuation of the pituitary response to GnRH increases with the degree of ovarian hyperstimulation. It is suggested that the responsible unspecified ovarian factor(s) exerts its effects at least at the pituitary level. PMID- 2110045 TI - Gonadotrophin secretion in the second half of the menstrual cycle: a comparison of women with normal cycles, luteal phase defects and disturbed follicular development. AB - In order to study the relationship between episodic gonadotrophin secretion and alterations of ovarian hormone secretion, we examined women with normal menstrual cycles (n = 26), luteal phase defects (n = 10) or disturbed follicular oestradiol secretion (n = 8) as established by daily (except weekends) determinations of oestradiol and progesterone. Pulsatile gonadotrophin secretion was studied during the luteal phase or the second half of the menstrual cycle sampling at 15 min intervals for 12 h. LH and FSH mean concentrations and LH pulse frequency were significantly (P less than 0.01) increased in the group with disturbed follicular development in the presence of decreased oestradiol (E2) and progesterone (P4) levels. In women with luteal phase defects mean LH and FSH concentrations and pulsatile LH secretion showed a nonsignificant trend to lower values in the presence of significantly decreased P4 concentrations during the luteal phase. PMID- 2110046 TI - Ovarian sensitivity to gonadotrophins in patients with PCO is unaffected by suppression of LH. AB - Infertile women with oligomenorrhoea and elevated LH concentrations (presumed polycystic ovary disease, PCO) were treated with exogenous gonadotrophins, HMG and HCG, for induction of follicular growth and ovulation, respectively. This was effected in the absence or presence of a gonadotrophin releasing hormone analogue (GnRH-A) to suppress basal LH and the positive feedback surge of LH. Analyses of the duration of HMG therapy required to attain the degree of stimulation for HCG to be administered showed no difference between those with and without LH suppression. Analyses of the ultrasound estimations of rates of follicle growth and continued recruitment during the course of HMG also failed to show any effect of LH suppression. These data show that the high sensitivity of these patients to HMG is not related to the circulating LH concentrations. PMID- 2110047 TI - Serum inhibin levels during the periovulatory interval in normal women: relationships with sex steroid and gonadotrophin levels. AB - Inhibin is a gonadal glycoprotein believed to be important in the regulation of pituitary FSH secretion and/or to function as a paracrine factor within the ovary and testis. We studied serum levels of inhibin, oestradiol (E2), progesterone (P), FSH and LH during the periovulatory interval in order to determine whether there is differential control of sex steroid and inhibin secretion by the mature follicle and the emerging corpus luteum. Seven normal cyclic women were admitted 3-4 days prior to midcycle and blood samples drawn every 3 h for 5-7 days. Serum E2, P, FSH, LH and inhibin were measured by radioimmunoassay. Data were normalized around the peak LH value (0 h). Serum E2 and inhibin rose in parallel (r = 0.92, P less than 0.001) between -69 and -18 h, E2 reached a peak of 1296 +/ 154 (mean +/- SEM) pmol/l at -18 h, then fell to 1050 +/- 139 pmol/l at 0 h. Serum inhibin, on the other hand, continued to rise to a peak of 837 +/- 95 U/l at -6 h, fell to 455 +/- 48 U/l at +45 h, then rose again. On average, the peak inhibin level occurred 10.4 +/- 5.1 h after the peak E2 (P less than 0.05). Inhibin levels were positively correlated with both serum LH and FSH between -24 and +24 h (P less than 0.01). Serum E2 was negatively correlated with LH, FSH and inhibin between -24 and 0 h (P less than 0.01). Serum P levels increased from 1.8 +/- 0.3 nmol/l at -24 h to 14.3 +/- 1.0 nmol/l at +60 h. Serum inhibin was positively correlated with serum P from -24 to 0 h (P less than 0.01) and +45 to +60 h (P less than 0.01), but was inversely correlated from 0 to +45 h (P less than 0.01). We conclude that the maturing follicle secretes both E2 and inhibin in parallel until -18 h, at which time the process of luteinization is initiated by the onset of the midcycle LH surge, as evidenced by the rise in P. E2 secretion then falls while inhibin secretion rises, indicating different regulation of secretion of these two hormones by the maturing follicle. Furthermore, the close positive correlation between inhibin and gonadotrophin levels around midcycle suggests that FSH and/or LH stimulate inhibin secretion and that the presumed negative feedback effect of inhibin on FSH secretion is overcome at this time. After midcycle, inhibin secretion initially falls, then rises, while P rises progressively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2110048 TI - Testosterone reduces the bioactivity of luteinizing hormone (LH) in man. AB - The effect of testosterone on LH bioactivity was investigated in six adult men (aged 40-56 years) with primary hypogonadism. Two men received a 400 mg testosterone implant, another two 800 mg, and the final two patients received both doses in consecutive courses separated by at least 4 weeks. Plasma samples, obtained before and at 1, 2, 4, 8, 16 and 24 weeks after treatment, were analysed for bioactive LH by the mouse Leydig cell bioassay, and immunoreactive LH and testosterone (T) by standard radioimmunoassays. The bioactive to immunoreactive (B:I) LH ratio, an index of LH biopotency, was calculated and the results compared with those from a group (n = 17) of healthy adult men. Before treatment, both bioactive and immunoreactive LH levels in the patients were higher and T levels lower than in the normal men (P less than 0.001). The mean +/- SD B:I LH ratio (3.5 +/- 0.6) in the patients was greater (P less than 0.05) than in the controls (2.7 +/- 0.7), indicating that in primary testicular failure, increased amounts of LH with enhanced bioactivity are secreted. Following T administration, a dose-related increase in circulating T and a reciprocal decrease in LH levels was observed between 1 and 16 weeks of treatment. However, there was a more pronounced decline in bioactive rather than immunoreactive LH levels, so that the B:I LH ratios decreased (P less than 0.001) from basal values after treatment. There was a negative correlation (r = -0.82, P less than 0.001) between circulating T levels and B:I LH ratios; the stronger the feedback signal, the lower the B:I LH ratio. It is concluded that testosterone negative feedback modifies not only the quantity but also the biological quality of secreted LH. PMID- 2110049 TI - Phosphorylated and dephosphorylated myosin light chains of Drosophila fly and larva. AB - 1. The present study confirmed that light chains of Drosophila adult fibrillar (flight) muscle myosin consist of Lf1, Lf2, Lf2' and Lf3, and tubular muscle myosin light chains contain Lt1, Lt2, Lt2' and Lt3, as revealed by two dimensional (isoelectric focusing and SDS-gel electrophoresis) gel electrophoresis. 2. Larva myosin light chains were of all the tubular type. However, it was found that Lt1 and Lt2' are produced by phosphorylation of Lt2, and Lf1 is produced by phosphorylation of Lf2'. 3. Injection of radioactive phosphate into Drosophila fly resulted in phosphorylations of Lf1 and Lt1. When larva or late pupa myosin was incubated with myosin light chain kinase from chicken gizzard or adult flies, phosphorylation of Lt1, Lf2' and Lt2' occurred. Drosophila myosin light chain kinase phosphorylated Lf1 in addition to Lt1 and L2' (Lf2' + Lt2') of adult myosin. 4. Dephosphorylation of adult myosin by potato acid and calf intestine alkaline phosphatases led to the shift of Lf1 (34,000), Lt1 (31,000) and L2' (Lf2' + Lt2') (30,000) to L2 (Lf2 + Lt2) positions (30,000). 5. Peptide mapping analyses revealed that larva Lt1, Lt2', Lt2 and adult Lt1 were all the same; therefore, it is thought that a single species of Lt2 specific to the tubular type of myosin and its phosphorylated isoforms (Lt1, Lt2') exist. 6. The peptide map of Lf1 was slightly different from that of Lt1, but very similar to that of L2' in adult myosin. L2 and L2' of adult myosin showed very similar peptide maps, but there were several different peptide fragments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110050 TI - Partial amino acid sequence of erythrocyte carbonic anhydrase from tiger shark. AB - 1. A partial primary structure (197 residues) of carbonic anhydrase from tiger shark (Galeocerdo cuvieri) erythrocytes has been determined. 2. The amino acid sequence of the enzyme is identical to those of human cytoplasmic carbonic anhydrases (CA I-III) by as much as 52-60%. 3. It is shown that tiger shark CA most closely resembles the CA II isoenzyme of amniotes. 4. Isoelectric focusing and inhibition studies on carbonic anhydrase from dogfish (Squalus acanthias) blood and muscle indicate the presence of the same isoenzyme in shark blood and muscle. PMID- 2110051 TI - Comparative gene frequencies of nucleoside phosphorylase from cattle of Bos taurus and Bos indicus derivation in Brazil. AB - 1. Two nucleoside phosphorylase (NP) phenotypes were detected in 844 animals from four distinct genetic groups of Bos taurus and Bos indicus derivation. 2. Bos indicus breeds like Guzerat (Kankrej), Gir, Nellore (Ongole) and Indubrazil presented an NP-H frequency of 1.00, 0.928, 0.776 and 0.754 respectively, while the Canchim breed, a Bos taurus-Bos indicus crossbred cattle (5/8 Charolais-3/8 Zebu) presented a frequency of 0.372. 3. The high frequency detected from the NP H allele in the Bos indicus breeds strongly suggests that this enzyme is a genetic marker for cattle and that it probably has a very high frequency in all Indian breeds. PMID- 2110052 TI - Antimycobacterial antibody levels in pleural fluid as reflection of passive diffusion from serum. AB - The objective of this study was the prospective evaluation of the relationship between serum and pleural fluid antibody levels to mycobacterial antigens and their role in the diagnosis of tuberculous pleuritis. The setting was a tertiary care medical center. Thirteen patients with tuberculous pleuritis and 53 control subjects with pleural effusion (22 with carcinoma, 17 with cardiac failure, and 14 with empyema or parapneumonic effusion) were studied. The level of IgG was measured by ELISA. The median titers of antibody to both Mycobacterium tuberculosis and M avium were significantly higher in the serum and pleural fluid of the patients with tuberculosis than in the control patients. There was a very close relationship between the levels of M tuberculosis (r = 0.95) and M avium (r = 0.94) antibodies in the serum and pleural fluid. We concluded that the levels of antimycobacterial IgG in pleural fluid, adjusted to constant protein concentration, are very closely related to the serum levels. Therefore, these antibodies in the pleural fluid probably result from passive diffusion from serum and not local production. Measurement of pleural fluid antibody levels will not add diagnostic sensitivity or specificity to that achieved with serodiagnosis. PMID- 2110053 TI - Use of tissue plasminogen activator in the coronary care unit for acute closure after coronary angioplasty. AB - Coronary angioplasty in a patient ten days following myocardial infarction was complicated by repeated thrombotic occlusion requiring intracoronary streptokinase. Recurrence of chest pain and ST elevations after transfer to the coronary care unit was successfully managed with intravenous tissue plasminogen activator without returning the patient to the catheterization laboratory. PMID- 2110054 TI - Potential economic impact of applying DRG-based prospective payment categories to inflammatory bowel disease patients. AB - New incentives regarding delivery of inpatient care by physicians and administrators have resulted from Medicare's DRG-based prospective reimbursement system. As these payment systems become widely adopted by other third-party payors, implications for adequate hospital reimbursement and quality inpatient care will intensify. This study of inflammatory bowel disease inpatients examines discharge data for 300 patients comprising 507 admissions from 1983 to 1987 at a large tertiary center hospital. While only 10.8% of these discharges were Medicare patients, all discharges were assigned a diagnosis-related-group reimbursement to derive a theoretical monetary loss or gain for the hospital. Overall hospital losses averaged $127.24 per case for this patient population, in which the medical and pediatric cases were adequately reimbursed, and the surgical admissions represented greater losses. The average length of stay for all patients decreased from 11.9 to 7.4 days over the study period, mostly a result of reductions in surgical hospital stays. We conclude that reimbursement for medical and pediatric discharges under DRG 179 appear adequate for this hospital, while surgical inflammatory bowel disease reimbursement is not. These data will be useful for comparison of future trends of inpatient utilization for inflammatory bowel disease patients as prospective reimbursement practices become more widespread. PMID- 2110055 TI - Maternal effect on micronucleus induction in MS/Ae mice. AB - MS/Ae mice, which are mutagen-sensitive in both the dominant lethal test and micronucleus test, and CD-1 mice, which are the parental strain of MS/Ae, were mated in all four possible combinations. Both male and female offspring were subjected to the micronucleus test using mitomycin C (MMC), colchicine (Col), and 6-mercaptopurine (6-MP). Col showed equivocal results. However, MMC and 6-MP showed differential responses in that both male and female offspring from CD-1 dams had lower incidences of micronucleated polychromatic erythrocytes than those from MS/Ae dams regardless of sire strain. In addition, body weights of offspring from MS/Ae dams were lower than those from CD-1 dams regardless of sire strain. Numbers of offspring from MS/Ae dams tended to be smaller than those from CD dams. These results suggest that the traits of MS/Ae mice are associated more with maternal factors than with paternal ones. PMID- 2110056 TI - A low-molecular-mass Kazal-type protease inhibitor isolated from rat hepatocytes is identical to rat pancreatic secretory trypsin inhibitor II. Purification and amino acid sequence. AB - A low-molecular-mass serine protease inhibitor was purified from hepatocytes and liver of rats. It was found to be a single polypeptide of 56 amino acid residues corresponding to Mr = 6224, a value that is in agreement with the molecular mass determined by gel chromatography. The inhibitor formed a complex in a molar ratio of 1:1 with trypsin. Its complete amino acid sequence was identical with that of pancreatic secretory trypsin inhibitor II (PSTI-II) in pancreatic juice, but not with that of PSTI-I [Uda, K., Ogawa, M., Shibata, T., Murata, A., Mori, T., Kikuchi, N., Yoshida, N., Tsunasawa, S. & Sakiyama, F. (1988) Biol. Chem. Hoppe Seyler 369, 55-61]. PSTIs have been reported to be primarily pancreatic secretory products, but in have been reported to be primarily pancreatic secretory products, but in patients immunoreactive PSTI was found in the plasma and urine during acute inflammatory disease and shown to be produced ectopically in cancer tissues. Here we report for the first time that PSTI-II is present in other normal tissues besides the pancreas. PMID- 2110057 TI - Studies on prophenoloxidase activation in the mosquito Aedes aegypti L. AB - This study, the first of its kind in a mosquito vector species, demonstrates the feasibility of studying prophenoloxidase activation in an insect containing not more than a few microliters of hemolymph. Mosquito phenoloxidase was found to be in an inactive proenzyme form, prophenoloxidase. Mosquito prophenoloxidase required bivalent cation for its activation; Ca2+ was found to be the most efficient for activation. Concomitant amidase activity was also observed prior to phenoloxidase activity. Through Western blotting, using a cross-reactive silkworm antiprophenoloxidase antibody, our results strongly suggest that mosquito prophenoloxidase activation resulted from limited proteolysis. Protease inhibitor studies reinforced this contention showing the involvement of (a) serine protease(s) with trypsin-like activity in the activation of mosquito prophenoloxidase. PMID- 2110058 TI - Characterization of the translational start site for IF2 beta, a short form of Escherichia coli initiation factor IF2. AB - The gene for initiation factor IF2, infB, represents one of the few examples in Escherichia coli of genes encoding two protein products in vivo. In a previous work, our group showed that both forms of IF2 (alpha and beta) are closely related and may arise from two independent translational events on infB mRNA. Unambiguous mapping and rigorous determination of the nature of the initiation triplet for IF2 beta, the smaller form of IF2, is critical for future mutagenesis of this codon, required for investigating the biological importance of both IF2 alpha and IF2 beta. Three types of experiments were carried out. First, a 77-bp deletion was created at the beginning of the structural gene leading to premature termination of IF2 alpha synthesis. Under these conditions, IF2 beta is still formed. Second, various Bal31 digests of infB containing the 77-bp deletion were fused to lacZ. Any synthesis of a fused protein with beta-galactosidase activity should reflect the occurrence of an initiation event on the messenger corresponding to this DNA segment. It was consequently possible to locate the IF2 beta initiation site within an 18-base region containing an in-phase GUG codon. Third, to avoid any artefactual reinitiation event possibly occurring under our experimental conditions, we fused to lacZ an infB fragment devoid of IF2 alpha start sequences but containing genetic information for this 18-base region. A hybrid protein with beta-galactosidase activity was synthesized. Moreover, its NH2-terminal amino acid sequence coincided with that of IF2 beta, demonstrating that GUG, located 471 bases downstream from the IF2 alpha external start codon, is the internal start codon for the shorter form of IF2. PMID- 2110059 TI - Properties and primary structure of the L-malate dehydrogenase from the extremely thermophilic archaebacterium Methanothermus fervidus. AB - L-Malate dehydrogenase from the extremely thermophilic mathanogen Methanothermus fervidus was isolated and its phenotypic properties were characterized. The primary structure of the protein was deducted from the coding gene. The enzyme is a homomeric dimer with a molecular mass of 70 kDa, possesses low specificity for NAD+ or NADP+ and catalyzes preferentially the reduction of oxalacetate. The temperature dependence of the activity as depicted in the Arrhenius and van't Hoff plots shows discontinuities near 52 degrees C, as was found for glyceraldehyde-3-phosphate dehydrogenase from the same organism. With respect to the primary structure, the archaebacterial L-malate dehydrogenase deviates strikingly from the eubacterial and eukaryotic enzymes. The sequence similarity is even lower than that between the L-malate dehydrogenases and L-lactate dehydrogenases of eubacteria and eukaryotes. The phylogenetic meaning of this relationship is discussed. PMID- 2110060 TI - Translational regulation of M13 gene II protein by its cognate single-stranded DNA binding protein. AB - To unravel the mechanism by which the single-stranded DNA binding protein encoded by gene V of the filamentous phage M13 regulates the synthesis of its cognate DNA replication protein encoded by gene II, an in vivo test system has been developed. The system consists of two recombinant plasmids with compatible replication origins. One plasmid contains M13 gene V under the control of the inducible araB promoter of Salmonella typhimurium. The other plasmid contains a fusion gene, whose expression is dependent upon the M13 gene-II-promoter and which consists of the 5' end of M13 gene II and the 5'-truncated beta galactosidase gene of Escherichia coli. Induction of the synthesis of wild-type gene V protein by arabinose resulted in a specific reduction of both the beta galactosidase activity and the amount of fusion protein produced. These specific inhibitory effects were not observed when the synthesis of the fusion protein was studied in the presence of an amber mutant of gene V. Comparison of the relative concentrations of the fusion protein mRNAs, as present in arabinose-induced and noninduced cells, provided solid and direct evidence for the conclusions made in earlier publications, that gene V protein exerts its regulatory effect at the level of translation. Since the transcript of the fusion gene only contains the first 74 nucleotides of gene II mRNA, it is furthermore concluded that these nucleotides are already sufficient for gene V protein to exert its regulatory effect. PMID- 2110061 TI - Vinculin is a permanent component of the membrane skeleton and is incorporated into the (re)organising cytoskeleton upon platelet activation. AB - Vinculin, a 130-kDa protein discovered in chicken gizzard smooth-muscle cells and subsequently also described in platelets, is believed to be involved in membrane cytoskeleton interactions. In this study we investigated vinculin distribution in human blood platelets. Two skeletal fractions and a remaining cytosolic fraction were prepared with a recently described Triton X-100 lysis buffer causing minimal post-lysis breakdown by proteolysis. The presence of vinculin was demonstrated in the membrane skeleton and cytosol of resting and thrombin-activated human platelets. Upon thrombin stimulation vinculin also appeared in the cytoskeleton. this cytoskeletal incorporation was completed during the early stages of platelet aggregation and secretion, when the uptake of myosin, actin-binding protein and talin was still not maximal. We conclude therefore, that vinculin may play an important role in the structural (re)organisation of the human platelet cytoskeleton upon platelet activation. PMID- 2110062 TI - Affinity labelling of a partially purified ecdysteroid receptor with a bromoacetylated 20-OH-ecdysone derivative. AB - The novel bromoacetyl ecdysteroid IV, (20R,22R)-2 beta,3 beta,14 alpha,20,22,25 xi-hexahydroxy-26-(3- bromoacetoxypropyl)-5 beta-cholest-7-en-6-one, BAEIV, has been synthesized by extending the side chain on C26 of 20-OH-ecdysone. BAEIV meets all the requirements for an affinity-labelling reagent. It reacts with the partially purified ecdysteroid receptors of Drosophila melanogaster rapidly and almost quantitatively. Reactions require only micromolar concentrations of BAEIV. The rate of the affinity-labelling reaction is determined by the association of BAEIV with the ecdysteroid receptor. The value of the apparent reaction rate constant is very similar to that of the association rate constant for the binding of 20-OH-ecdysone to the ecdysteroid receptor. Product analysis of the reaction of [14C]BAEIV with the ecdysteroid receptor revealed two labelled peptides having molecular masses 150 kDa and 90 kDa. The smaller peptide is possibly a proteolytic fragment of the larger peptide. The identification of a 150-kDa peptide by chemical affinity labelling of the ecdysteroid receptor agrees with previously reported photoaffinity-labelling results from our laboratory. The results also demonstrate that the ecdysteroid receptor of D. melanogaster has a molecular mass higher than all other vertebrate steroid hormone receptors studied so far. PMID- 2110063 TI - Further studies on the role of glycogenin in glycogen biosynthesis. AB - About 90% of the glycogenin in skeletal muscle extracts prepared from fed, 24-h starved or alloxan-diabetic rabbits sedimented at 140,000 x g with the glycogen/sarcovesicular fraction, from which it was released by glycogenolysis, but not by 1% SDS. Glycogenin in the glycogen/sarcovesicular fraction is therefore bound covalently to glycogen, and not associated (covalently or non covalently) with the sarcoplasmic reticulum. The same proportion of glycogen synthase was also recovered in the glycogen/sarcovesicle fraction, was solubilised by glycogenolysis, and copurified with glycogenin to yield a heterodimer composed of a 1:1 complex between these proteins. Glycogen synthase and glycogenin are therefore present in equimolar amounts in skeletal muscle and there is an average of one glycogen synthase catalytic subunit associated with each molecule of glycogen in vivo. Glycogenin and glycogen synthase released into the muscle cytosol by degradation of glycogen did not form a complex initially, and only 50% reassociation took place after storage for several hours or overnight dialysis. This suggests that the muscle cytosol may contain a factor(s) which regulates glycogen biogenesis by modulating the association of glycogenin and glycogen synthase. Only glycogen synthase that was complexed to glycogenin was capable of elongating the primer formed by incubation of glycogenin with Mn2+ and micromolar concentrations of UDP-glucose, demonstrating the critical importance of this complex for glycogen biogenesis. PMID- 2110064 TI - ECG evidence of limited myocardial infarction following coronary occlusion treated by early intravenous rt-PA infusion. AB - Serial 12-lead surface electrocardiograms (ECGs) were analysed in 110 patients with first evolving myocardial infarction entered in a double-blind placebo controlled trial of intravenous rt-PA within 2.5 h (mean 1.9 +/- 0.5 (SD)) of pain onset. ECG analysis was performed by two 'blinded' analysts. QRS scoring (by the modified Selvester method) was used as an index of myocardial necrosis. Patient results were analysed according to infarct location. There was no difference between the two treatment groups in ST-segment elevation or QRS score at entry or up to 24 h after symptom onset. However from 24 h, QRS score was lower in patients with anterior infarction given rt-PA than in those given placebo: 5.4 +/- 2.8 vs 7.7 +/- 4.1 (P = 0.02) at 48 h; 4.7 +/- 3.2 vs 8.0 +/- 4.0 (P = 0.01) at 4-10 days; and 4.6 +/- 3.9 vs 7.5 +/- 3.9 (P = 0.01) at 21 days. For patients with inferior infarction, rt-PA treatment also resulted in a lower QRS score although this was not significantly different from the score of the placebo group (P = 0.07). Comparison of QRS scores with ejection fraction measured from the contrast ventriculogram taken at 21 days showed a moderate correlation (r = 0.46) in patients with anterior infarction but a poor correlation in patients with inferior infarction. These ECG results indicate that in evolving anterior myocardial infarction, there is limitation of infarct size from early rt-PA infusion. PMID- 2110065 TI - Diazepam and Ro 15-1788 increase absence epilepsy in WAG/Rij rats chronically exposed to diazepam. AB - The mechanisms underlying tolerance to benzodiazepines were investigated by injecting diazepam (5 mg/kg) twice daily for 23 days in WAG/Rij rats (an animal model for non-convulsive absence epilepsy). After this the rats received either the agonist, diazepam, or the antagonist, flumazenil (Ro 15-1788). EEG analyses showed that both compounds increased the amount of absence epilepsy-like phenomena. This suggests that repeated administration of diazepam moves the benzodiazepine receptor spectrum towards the inverse agonist end. PMID- 2110066 TI - Pertussis toxin inhibits endothelium-dependent relaxations evoked by fluoride. AB - Fluoride is a direct activator of G-proteins. In isolated rings of canine coronary artery, fluoride caused relaxation of rings with endothelium, but only slight contraction of rings denuded of endothelium. The endothelium-dependent relaxations to fluoride were inhibited by pertussis toxin, an inhibitor of G proteins, or by methylene blue, an inhibitor of soluble guanylate cyclase. Therefore, fluoride causes endothelium-dependent relaxations in part by activating a pertussis toxin-sensitive G-protein in the endothelial cells. PMID- 2110067 TI - Characterisation of the discriminative stimulus properties of flumazenil. AB - Rats were trained to discriminate flumazenil (15 mg/kg i.p.) from vehicle in a two-lever, food-reinforced, operant conditioning procedure. Substitution tests were performed with a wide dose range of flumazenil and of several benzodiazepines and non-benzodiazepine compounds possessing behavioural effects similar to or opposite to those of benzodiazepine agonists. The results indicate that low doses of flumazenil have behavioural effects, that the flumazenil cue has a low degree of specificity and is most strongly related to the stimulus properties of benzodiazepines. PMID- 2110068 TI - Distension-induced secretion in the rat colon: mediation by prostaglandins and submucosal neurons. AB - Distension of the rat colon descendens in vitro by a hydrostatic gradient induced an increase in short-circuit current (Isc). In a mucosa-submucosa preparation containing the plexus submucosus, the increase in Isc was biphasic with a half time of about 200 s for the spontaneous returning to the baseline. The time course was monophasic in a mucosa preparation without the plexus submucosus. The increase in Isc in the mucosa-submucosa preparation was inhibited by an inhibitor of phospholipase A2, quinacrine, and by indomethacin, tetrodotoxin or atropine; each of these compounds also abolished the second phase of the response. In contrast, only indomethacin was effective in reducing the increase in Isc in the mucosa preparation. In both preparations the response to distension was inhibited by scilliroside, by replacement of Cl- with gluconate, and by administration of frusemide or the chloride channel blocker, anthracene-9-carboxylic acid. The results indicate that distension induces chloride secretion by causing the release of prostaglandins, which act indirectly, i.e. mediated by the submucosal plexus, and directly at the epithelium. PMID- 2110070 TI - Treatment of clomiphene citrate-resistant polycystic ovarian syndrome with pure follicle-stimulating hormone or human menopausal gonadotropin. AB - Two hundred ten treatment cycles of follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG) were completed in 49 patients with clomiphene citrate-resistant polycystic ovarian syndrome. The results from 68 cycles of daily intramuscular (IM) FSH and 41 cycles of IM hMG were compared. The ovulation rate, maximum serum estradiol (E2) levels achieved, and pregnancy rate were similar in both groups, but FSH resulted in significantly fewer follicles developing and hyperstimulation. The 68 cycles of daily IM FSH were further compared with the outcome of administering the FSH as an alternate-day IM injection in 70 cycles, and by subcutaneous pulsatile injection in 31 cycles. There were no differences in any of the parameters measured between daily and alternate-day FSH. Pulsatile FSH required a greater total dose over a longer period of time to achieve stimulation. It also produced fewer follicles, a lower maximum serum E2 level, and the lowest incidence of hyperstimulation. Twenty pregnancies resulted, of which 6 aborted in the first trimester; there was 1 set of twins and 13 singleton pregnancies. The cumulative pregnancy rate after 6 treatment cycles was 62%. PMID- 2110069 TI - Protein kinase C-regulated production of prostacyclin by rat endothelium is increased in the presence of lipoxin A4. AB - Prostacyclin is generated by cultured rat endothelial cells. Compound blocking activity of protein kinase C and cyclic nucleotide-dependent protein kinases (H7) and compound blocking interaction between Ca2+ and calmodulin (W7) diminish generation of prostacyclin in rat endothelial cells. These compounds give a synergistic effect when they are introduced to the endothelial cell cultures simultaneously. Compound HA1004, an inhibitor of cAMP- and cGMP-dependent protein kinases has no effect on prostacyclin generation. Lipoxin A4, a potent direct stimulator of protein kinase C, rapidly induces prostacyclin generation in rat endothelium in a dose- and time-dependent fashion. Lipoxin A4-induced generation of prostacyclin can be inhibited by H7 and W7 but not by HA1004. Lipoxin B4 has no significant effect on prostacyclin generation in rat endothelium. In conclusion, our results demonstrate that generation of prostacyclin by rat endothelial cells is regulated via a pathway involving protein kinase C and Ca2+. PMID- 2110071 TI - Stimulation with human menopausal gonadotropin versus follicle-stimulating hormone after pituitary suppression in polycystic ovarian syndrome. AB - Stimulation with human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) was compared in 34 patients with polycystic ovarian syndrome after pituitary gonadotrope suppression with buserelin acetate. No differences were seen in the hormone parameters observed. Also, the duration of the stimulation period and the dose of gonadotropin used were the same. In both groups a multifollicular response was seen. Oocyte retrieval and in vitro fertilization resulted in identical ratios of mature to total oocytes and cleavage rates. Nine pregnancies occurred, four in the hMG group and five in the FSH group. Of the nine pregnancies, two were the result of transfer of frozen-thawed embryos in estradiol and progesterone substituted cycles. PMID- 2110072 TI - Clinical features of young women with hypergonadotropic amenorrhea. AB - One hundred fifteen women under age 40 presenting with hypergonadotropic amenorrhea (follicle-stimulating hormone greater than 40 mIU/mL) were evaluated. Incomplete pubertal maturation and chromosomal abnormalities were more likely in the 18 women (15.7%) with primary amenorrhea than in those with secondary amenorrhea. The 97 women with secondary hypergonadotropic amenorrhea were significantly more apt to complain of symptoms of estrogen deficiency, have been pregnant before diagnosis, and have evidence of ovulation after diagnosis. Withdrawal bleeding occurred commonly (greater than 48%) in those women administered exogenous progestin. Immune abnormalities occurred with approximately equal frequency (17.4%), and spinal bone density was decreased in both groups. PMID- 2110073 TI - Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea. AB - The efficacy of a technique of gonadotropin suppression and human menopausal gonadotropins (hMG) to induce ovulation in women with hypergonadotropic amenorrhea was evaluated in 100 consecutive women. Ovulation was achieved in 19% of cycles (68/361), the pregnancy rate per cycle was 5.2% (19/361), and the viable pregnancy rate was 2.2% (8/361). In the majority of the successful cases, estrogen was used to decrease the elevated luteinizing hormone and follicle stimulating hormone levels, especially where the ethinyl estradiol therapy alone induced a rise in endogenous 17 beta-estradiol levels with hMG used to boost the follicle to maturation. Although the success rate is low, this technique can result in some successes in otherwise almost hopeless cases. PMID- 2110074 TI - Risk of a second consecutive first-trimester spontaneous abortion in women who conceive with menotropins. AB - It is generally recognized that a spontaneous abortion rate of approximately 25% exists in human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) induced pregnancies. Despite this, little is known regarding the prognosis of future menotropin-induced pregnancies in women who abort in their first hMG pregnancy. We retrospectively reviewed the obstetrical outcome of women who achieved two or more menotropin pregnancies between the years 1980 and 1987. Nineteen of 40 patients (48%) whose first hMG pregnancy ended in an early spontaneous abortion went on to abort in a second hMG pregnancy, as compared with only 1 of 15 women (6.7%) whose first hMG pregnancy was successful. Age, parity, weight, height, and plasma estradiol levels at hCG administration did not differ between the two groups. From this data we conclude that women whose first hMG pregnancy results in a spontaneous abortion are at high risk for another spontaneous abortion in a subsequent menotropin conception. PMID- 2110075 TI - Identification of low and high molecular weight follicle-stimulating hormone receptor-binding inhibitors in human follicular fluid. AB - Various fractions of human follicular fluid (FF) were tested for follicle stimulating hormone (FSH) receptor-binding inhibitory activity, as well as for their ability to form a dansyl derivative previously reported to be associated with FSH receptor-binding inhibitory activity in bovine FF. Pooled human FF was found to inhibit binding of radioiodinated human FSH (125I-hFSH) to its receptor in a concentration-related manner. Fractionation of human FF by sequential ultrafiltration through membranes of calibrated pore size resulted in human FF components of low (500 to 5,000) and high (greater than 5,000) molecular weight, (Mr) respectively. Each of these inhibited 125I-hFSH binding to receptor in a concentration-related manner. Dansylation of the above components revealed the Rf = 0.15 dansyl derivative to be present in unfractionated human FF and in the low (500 to 5,000 Mr), but not the high (greater than 5,000 Mr), component of human FF. These findings are consistent with those previously reported for bovine FF and porcine FF and indicate that human FF contains FSH receptor-binding inhibitors with properties similar to those observed in animal species. PMID- 2110076 TI - Ovarian stimulation protocol for in vitro fertilization with gonadotropin releasing hormone agonist widens the implantation window. AB - Pregnancy rates vary considerably with the type of ovarian stimulation used for in vitro fertilization and embryo transfer (IVF-ET). The window of implantation may represent one of the rate-limiting steps in IVF success. We therefore investigated estimated implantation times of 10 consecutive IVF singleton pregnancies, achieved using pituitary suppression with gonadotropin-releasing hormone agonist (GnRH-a) before and during ovarian stimulation with human menopausal gonadotropins (hMG), and compared those with 9 consecutive IVF pregnancies achieved by hMG stimulation only. Estimated implantation times were calculated by regression analysis of serial human chorionic gonadotropin (hCG) measurements between days 7 and 16 after ET. The GnRH-a/hMG pregnancies implanted between days 7 and 11, whereas hMG pregnancies implanted between days 7 and 9 after ET. The hCG regression curve for the GnRH-a/hMG pregnancies revealed a delay of 1.5 days in estimated implantation time compared with the hMG only group. There were no significant differences in pretransfer in vitro embryos development between the two groups. Thus, the delay in hCG rise probably reflects a delay in embryo implantation. We therefore conclude that a GnRH-a/hMG stimulation protocol appears to widen the implantation window in comparison with a hMG only protocol. This observation may at least in part explain the improved IVF pregnancy success with GnRH-a/hMG stimulation protocols. PMID- 2110077 TI - Can premature luteinization in superovulation protocols be prevented by aspiration of an ill-timed leading follicle? AB - In 12 patients stimulated for in vitro fertilization and embryo transfer (IVF ET), a single leading follicle developed, whereas the other follicles were 6 mm smaller. In 7 patients chosen at random (group A), the leading follicle was aspirated, whereas in the other 5 the leading follicle was allowed to continue growing (group B). Comparison of the hormonal pattern of both groups showed that a premature luteinizing hormone (LH) surge was avoided only in group A, and only in this group a second follicle aspiration for IVF-ET was done, and two pregnancies were achieved. In group B, aspiration for IVF-ET was canceled because of premature LH surge. It is suggested that aspiration of a single leading follicle during ovulation induction may be an efficient method to avoid premature LH surge enabling other follicles to develop up to the preovulatory stage. PMID- 2110078 TI - Embryo implantation after human in vitro fertilization: importance of endometrial receptivity. AB - To study the effects of controlled ovarian hyperstimulation (COH) on endometrial receptivity during human in vitro fertilization (IVF), we compared embryo implantation data obtained from our nonanonymous donor oocyte program with those obtained from standard IVF. To control for embryo quality, IVF patient characteristics were matched to those of the oocyte donors with regard to age and previous gravidity. All cycles were performed in an identical manner, using standardized ovarian stimulation protocols, transvaginal follicle aspiration, fertilization and culture in vitro, and transcervical embryo transfer. A similar number of oocytes per cycle were obtained, fertilization rates were similar, and similar numbers of embryos were transferred in both groups. Transferred embryos had similar numbers of blastomeres and were morphologically judged to be of similar quality in both groups. Implantation rates per individual embryo were significantly higher in donor than in standard IVF (35% versus 10.7%) as were ongoing per embryo implantation rates (23% versus 8%). Clinical and ongoing pregnancy rates per cycle were likewise higher in the donor group than in the standard IVF group (67% versus 39%, and 61% versus 30%, respectively). We conclude that COH inhibits embryo implantation after IVF by decreasing endometrial receptivity, which is an important factor in IVF pregnancy success. PMID- 2110079 TI - Changes in gonadotropin and alpha-subunit secretion after a single administration of gonadotropin-releasing hormone antagonist in adult males. AB - The suppressive effect of the gonadotropin-releasing hormone (GnRH) antagonist Nal-Glu ([Ac-D2Nal1, D4ClPhe2, D3Pal3, Arg5, D-4-p-methoxybenzoyl-2-aminobutyric acid6, DAla10]-GnRH), injected intramuscularly with 5 mg, was studied in six men. Testosterone decreased by 87 +/- 2.3%, whereas the mean drops were 50 +/- 10%, 43 +/- 6.6%, and 39 +/- 5.6% for radioimmunoassayable luteinizing hormone (LH), follicle-stimulating hormone, and free alpha-subunit, respectively (mean +/- SEM). Immunological characteristics of plasma LH were modified during the inhibition and recovery phases as evidenced by comparison between polyclonal and monoclonal assays. In two additional subjects sampled every 10 minutes, both LH and alpha-subunit pulses were suppressed by NalGlu injection and restored by pulsatile GnRH infusion. However, a nonpulsatile and possibly non-GnRH-dependent alpha-subunit secretion was maintained after NalGlu administration. PMID- 2110080 TI - Why lose an in vitro fertilization cycle when stimulation fails? AB - Different protocols using agonists of GnRH-a have been proposed for the ovarian stimulation in IVF cycles. In case of stimulation failure with the flare-up protocol, we have investigated whether an immediate switch to pituitary blockade by the long-acting analog may avoid the cycle to be canceled. This procedure allows a rescue of cycles among poor responders and does not have any deleterious effect on the recruitment of follicles, oocyte quality, fertilization, and pregnancy rates. PMID- 2110081 TI - [Pulsatile secretion of ovarian steroids in the mid-luteal phase of the menstrual cycle]. AB - The possibility of the pulsatile secretion of pituitary gonadotropins (LH and FSH) and ovarian steroids (estradiol and progesterone) was studied. In addition, an evaluation was made of the regulatory factors for steroid secretion of corpus luteum in view of the response behavior of the secretion of LH, FSH, estradiol and progesterone when loaded with hCG and gonadotropin releasing hormone (Gn-RH). The study was performed on 9 cases of infertile women in the mid-luteal phase of a normal menstrual cycle. In 5 cases, blood was collected every 30 minutes and over 24 hours. Thereafter, 2,500 iu of hCG was given twice to another subject at 8 hour intervals, and blood was collected every 30 minutes from immediately after the 1st administration over 16 hours. In the other 3 cases, 15 micrograms of Gn RH was given at an interval of 90 minutes, and blood was collected every 20 minutes for 16-24 hours. Then, the frequency and amplitude of each pulse for LH, FSH, estradiol and progesterone were calculated under the modified Santen's rule in situ and when loaded with Gn-RH, and the relationship between pulses of gonadotropins and those of estradiol and progesterone was analysed by determining the number of concomitant pulses. The hormone dynamics when loaded with hCG were also assessed. The pulse frequency and amplitude in situ of each hormone were 10.6 +/- 0.8 times/24 h and 4.9 +/- 0.6 miu/ml for LH, 9.9 +/- 9.9 times/24h and 1.3 +/- 0.1 miu/ml for FSH, 9.2 +/- 0.9 times/24h and 34.3 +/- 2.7 pg/ml for estradiol, 7.4 +/- 0.5 times/24 and 3.7 +/- 0.4 ng/ml for progesterone. The coincidence of estradiol pulses and LH pulses was 37 times, and the concomitant ratio of LH pulse to estradiol pulse was 81%. The coincidence of progesterone pulses and LH pulses was 31 times, and the concomitant ratio of LH pulse to progesterone pulse was 84%. Furthermore, the concomitant ratio of FSH pulse to estradiol pulse or progesterone pulse was 61% or 70%, respectively. The mean plasma concentration of LH, estradiol and progesterone during 8 hours after the 1st administration and 2nd administration of hCG changed from 29.9 +/- 2.3 to 41.8 +/- 1.6 miu/ml, from 140.3 +/- 3.0 to 160.6 +/- 3.6 pg/ml and from 19.2 +/- 1.0 to 25.7 +/- 0.6 ng/ml, respectively. These values increased significantly after the second injection (P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2110082 TI - Purification of soluble enzymes from erythrocyte hemolysates by three phase partitioning. AB - 1. The three phase partitioning method of protein fractionation was successfully applied to human erythrocyte hemolysates for the removal of hemoglobin and the concentration of soluble enzymes. 2. Human carbonic anhydrase I and II, catalase and superoxide dismutase were recovered free of hemoglobin and in good yield in the initial partitioning step, with a 60- to 80-fold enrichment of enzyme activities. 3. After further purification, carbonic anhydrases I and II were obtained at overall yields of 84 and 29%, respectively, crystallized catalase at 38% and superoxide dismutase at 52%. PMID- 2110083 TI - Polyamine transport in mammalian cells. PMID- 2110085 TI - Diabetic autonomic neuropathy in BB rats and effect of ARI treatment on heart rate variability and vagus nerve structure. AB - The preventive effect of the aldose reductase inhibitor (ARI) ponalrestat on heart-rate variability and the development of autonomic neuropathy in the vagus nerve was investigated in the spontaneously diabetic BB rat. ARI treatment completely prevented the characteristic decrease in heart-rate variability and axonal atrophy of the vagus nerve for 4 mo in hyperglycemic BB rats. After 6 mo of treatment, the preventive effect on heart-rate variability was partial, and the vagus nerve demonstrated an increase in regenerating myelinated and unmyelinated fibers. These data suggest that autonomic neuropathy involving the vagus nerve is metabolically induced by demonstrating that inhibition of the polyol pathway significantly delays the occurrence of functional and structural autonomic neuropathy despite the presence of hyperglycemia. PMID- 2110084 TI - Isolation of two hemorrhagic toxins from Crotalus basiliscus basiliscus (Mexican west coast rattlesnake) venom and their effect on blood clotting and complement. AB - 1. Two hemorrhagic toxins of mol. wt 27,000 (B1) and 27,500 (B2) and pI 9.8 and 5.2 respectively were isolated from Crotalus basiliscus venom. 2. The two proteinases did not cross-react antigenically. 3. Both toxins caused hemorrhage in mice and each was capable of hydrolyzing hide power azure, casein, collagen and fibrin. 4. B1 hydrolyzed the A alpha, B beta and gamma chains of fibrinogen. B2 hydrolyzed the A alpha and B beta chains of fibrinogen, but not the gamma chain. 5. Both proteinases inactivated guinea pig complement. PMID- 2110086 TI - A survey of signs, symptoms and symptom control in 30 terminally ill children. AB - The notes of 30 terminally ill children with various diagnoses were searched for reports of symptoms that had occurred during their last month of life. All had stayed at Helen House, a hospice for children, for part or all of that time. The results were analysed for symptom frequency and resistance to treatment. Over four-fifths of the children were recorded as having pain in the last month of life. In a smaller number, symptoms such as muscle spasm and excessive secretions proved particularly difficult to control. The identification of symptoms in brain damaged and young children, and the control of some of the more resistant symptoms, are discussed. PMID- 2110088 TI - Effect of lipoxygenase inhibitors on Ca2(+)-induced constriction of the rabbit ear artery. AB - 1. The effects of nafazatrom, nordihydroguaiaretic acid (NDGA) and quercetin on Ca2(+)-induced vasoconstriction were studied in isolated rabbit ear arteries. 2. The arteries were perfused with Ca2(+)-free and high K+ (75 mM) Krebs bicarbonate buffer. Constriction of the artery was induced by addition of Ca2+ (1.5 mM) to the perfusion fluid. 3. Indomethacin (1 microM) did not alter the response to Ca2+. 4. Nafazatrom (2 or 5 microM) produced a concentration-dependent inhibition of the constrictor response to Ca2+ ranging from 4 to 23% after 1 hr of perfusion and 26 to 62% after 3 hr. 5. Similar effects were obtained with NDGA and quercetin (0.5 and 1 microM). 6. The inhibitory effects of nafazatrom and quercetin were antagonized by Ca2+ (2.5 mM) or Bay K 8644 (1 microM), a calcium channel activator. 7. Ca2(+)-induced contractions recovered within 30 min after discontinuation of perfusion with quercetin, whereas nafazatrom and NDGA had longer durations of action. 8. These results suggest that inhibitors of lipoxygenase antagonized Ca2(+)-induced vasoconstriction and that products of lipoxygenase metabolism may facilitate Ca2+ entry into vascular smooth muscle cells. PMID- 2110087 TI - Two distinct, divalent cation-sensitive, antagonist binding states of heart muscarinic receptors: differential modulation by guanine nucleotide. AB - 1. The binding of [3H]quinuclidinylbenzilate (QNB), a muscarinic antagonist, to cardiac muscarinic receptors was investigated in two subcellular fractions (washed particles and microsomes) isolated from rat heart atria and ventricles. 2. 5'-guanylylimidodiphosphate (Gpp(NH)p, 0.1 mM), increased (2-3-fold) the binding to washed particles, but not to microsomes, whereas Mg2+ (1-20 mM) increased (up to 5-fold) the binding to microsomes, but not to washed particles. Gpp(NH)p modestly increased the affinity while Mg2+ decreased the affinity towards the radiolabelled antagonist. 3. Treatment with N-ethylmaleimide (NEM, 2 mM) increased the antagonist binding to either fraction. The stimulatory effect of Gpp(NH)p was not evident while that of Mg2+ survived in the NEM-treated fractions. 4. The treatment of fractions with divalent cations chelators (EDTA, EGTA; 10 mM) augmented the stimulatory effect of Mg2+ on [3H]QNB binding to microsomes while that of Gpp(NH)p on the washed particle [3H]QNB binding was decreased. Such treatment further revealed an inhibitory action (about 40%) of Mg2+ on the washed particle binding. PMID- 2110089 TI - Levamisole inhibits in vivo rat platelet aggregation by a release of prostacyclin like factor. AB - 1. The anti-thrombotic effect of levamisole (LMS) and acetylsalicylic acid (ASA) were examined in vitro and in vivo models. 2. LMS inhibits rat platelet aggregation induced by either adenosine 5'-diphosphate (ADP) or collagen (CLG) in vitro and in vivo. 3. LMS is more active in vivo than in vitro while acetylsalicylic acid (ASA) is more active in vitro than in vivo. It seems that in vivo LMS does not act by blocking thromboxane A2 formation only, but via participation of an endogenous factor. 4. The release of LMS-induced anti thrombotic factor is inhibited by ASA pretreatment, indicating to be a cyclooxygenase metabolite of arachidonic acid. 5. The LMS-induced anti-thrombotic factor has a t1/2 of 3.6 +/- 0.8 min that is similar to the t1/2 of synthetic prostacyclin (PGI2) tested in our system (3.9 +/- 0.5 min; P = NS). 6. The release of PGI2-like substance from vascular tissue is LMS dose-dependent. PMID- 2110090 TI - Rapid purification of the peptide toxins microcystin-LR and nodularin. AB - An isolation procedure was developed to provide within one day microcystin-LR, a cyclic heptapeptide toxin from Microcystis aeruginosa PCC 7806. After ODS (octadecylsilyl) solid phase extraction, the crude toxin fraction was chromatographed using a strong anion exchange column. The toxin was eluted with 0.02 M ammonium bicarbonate. An at least 95% purity was revealed on HPLC separation by monitoring at 214 nm. Application of the procedure to the cyclic pentapeptide toxin nodularin from Nodularia spumigena AV2 was examined. PMID- 2110091 TI - Production and secretion of pertussis toxin subunits in Bacillus subtilis. AB - Pertussis toxin (PT) is a major component of today's acellular whooping cough vaccines. The use of acellular vaccines is predicted to increase sharply in the near future. There is therefore a need to produce PT in a way that makes its purification as easy as possible. Our approach was to express all five PT subunits individually in Bacillus subtilis. We have used vectors containing the promoter and signal sequences of the alpha-amylase gene of Bacillus amyloliquefaciens followed by an insert encoding the appropriate PT-subunit. All PT-subunits were secreted and found in the culture supernatant. The level of expression varied considerably: S1 and S5 were produced in large quantities whereas much smaller amounts of S2, S3 and S4 were found. The subunits were also present in the membrane fraction of the respective strains. PMID- 2110092 TI - Cloning and expression in Escherichia coli of tryptophan genes from Streptomyces griseus IMRU 3570. AB - Two Sau3A fragments of Streptomyces grisues IMRU 3570 were cloned in pBR322 as a vector. One of these clones contained the genetic information needed to complement trpA and trpB mutations in Escherichia coli. The other complements trpA, trpB and trpC mutations in E. coli. Both fragments originated in the same region of the chromosome but the latter is 1 kilobase (kb) longer in the region nearest the tetracycline promoter. PMID- 2110093 TI - Opacity factor from group A streptococci is an apoproteinase. AB - Opacity factor (OF) is an enzyme, elaborated by certain serotypes of group A streptococci, which produces opalescence in mammalian sera. OF has been designated a lipoproteinase. Lipoproteins are complex structures and many enzymes are involved in their catalysis. We therefore set out to establish which of the many enzymes OF could be. Results showed that OF rendered high density lipoprotein (HDL) insoluble, accounting for the opalescence in serum, and altered its electrophoretic mobility. Electron microscopy revealed that OF caused an aggregation of HDL and an alteration in molecule shape. OF specifically split apoprotein AI of HDL into two fragments demonstrable by SDS-PAGE. We therefore designate OF as an apoproteinase. PMID- 2110094 TI - An outer membrane protein characteristic of mucoid strains of Pseudomonas aeruginosa. AB - SDS-polyacrylamide gel electrophoresis of outer membrane (OM) proteins of different mucoid strains of P. aeruginosa revealed a protein of about 54 kDa that was absent in nonmucoid strains. This 54 kDa protein was expressed under iron restricted and iron sufficient growth conditions. Electrophoretic mobility of the 54 kDa protein was modified by the solubilization temperature as well as by the addition of lipopolysaccharide and alginate prior to electrophoresis. Treatment of OMs with octylglucoside/KCl or SDS completely extracted the 54 kDa protein at low temperatures. The possible role of this protein in biosynthesis and/or excretion of bacterial alginate is discussed. PMID- 2110095 TI - Cloning vectors, derived from a naturally occurring plasmid of Pseudomonas savastanoi, specifically tailored for genetic manipulations in Pseudomonas. AB - A minimal replicon of 1.8 kb isolated from a 10-kb plasmid of Pseudomonas savastanoi, pPS10, has been used to obtain a collection of small vectors specific for Pseudomonas (P. savastanoi, P. aeruginosa and P.putida). In addition, shuttle vectors that can be established both in Pseudomonas and Escherichia coli have been constructed by adding a pMB9 replicon. The vectors permit cloning of DNA fragments generated by a variety of restriction enzymes using different antibiotic resistance markers for selection and offer the possibility to screen recombinants by insertional inactivation. This cloning system can be used to establish recombinant plasmids in Pseudomonas either at low or high copy number. pPS10 derivatives are compatible with other Pseudomonas vectors derived from broad-host-range replicons of the incompatibility groups P1, P4/Q and W. Introduction and expression of the iaaMH operon in a P. savastanoi mutant deficient in the production of indoleacetic acid has been achieved using one of these vectors. PMID- 2110096 TI - Nucleotide sequence of the putative regulatory gene and major promoter region of the Streptomyces griseus glycerol operon. AB - Nucleotide sequencing of the deduced major promoter region of the glycerol utilization operon and an upstream regulatory gene of Streptomyces griseus reveals extensive similarity to the previously sequenced homologous S. coelicolor region [Smith and Chater, J. Mol. Biol. 204 (1988) 569-580]. However, regions showing extensive divergence are found in the noncoding parts of the sequence. These may help to evaluate the significance of various sequence features in relation to promoter activity. PMID- 2110097 TI - The 'effective number of codons' used in a gene. AB - A simple measure is presented that quantifies how far the codon usage of a gene departs from equal usage of synonymous codons. This measure of synonymous codon usage bias, the 'effective number of codons used in a gene', Nc, can be easily calculated from codon usage data alone, and is independent of gene length and amino acid (aa) composition. Nc can take values from 20, in the case of extreme bias where one codon is exclusively used for each aa, to 61 when the use of alternative synonymous codons is equally likely. Nc thus provides an intuitively meaningful measure of the extent of codon preference in a gene. Codon usage patterns across genes can be investigated by the Nc-plot: a plot of Nc vs. G + C content at synonymous sites. Nc-plots are produced for Homo sapiens, Saccharomyces cerevisiae, Escherichia coli, Bacillus subtilis, Dictyostelium discoideum, and Drosophila melanogaster. A FORTRAN77 program written to calculate Nc is available on request. PMID- 2110098 TI - Structurally stable Bacillus subtilis cloning vectors. AB - Cloning of long DNA segments (greater than 5 kb) in Bacillus subtilis is often unsuccessful when naturally occurring small (less than 10 kb) plasmids are used as vectors. In this work we show that vectors derived from the large (26.5 kb) plasmids pAM beta 1 and pTB19 allow efficient cloning and stable maintenance of long DNA segments (up to 33 kb). The two large plasmids differ from the small ones in several ways. First, replication of the large plasmids does not lead to accumulation of detectable amounts of ss DNA, whereas the rolling-circle replication typical for small plasmids does. In addition, the replication regions of the two large plasmids share no sequence homology with the corresponding regions of the known small plasmids, which are highly conserved. Taken together, these observations suggest that the mode of replication of the large plasmids is different from that of small plasmids. Second, short repeated sequences recombine much less frequently when carried on large than on small plasmids. This indicates that large plasmids are structurally much more stable than small ones. We suggest that the high structural stability of large plasmids is a consequence of their mode of replication and that plasmids which do not replicate as rolling circles should be used whenever it is necessary to clone and maintain long DNA segments in any organism. PMID- 2110100 TI - The structure of the trpE, trpD and 5' trpC genes of Bacillus pumilus. AB - The nucleotide (nt) sequences of the Bacillus pumilus trpE, trpD and 5' portions of trpC genes have been determined. Genetic analysis suggested the presence of an internal promoter upstream from the trpC gene, yet no typical consensus sequences were found. The nt and amino acid sequence homologies between the B. pumilus, Bacillus subtilis and Escherichia coli trp genes are presented. PMID- 2110099 TI - Cloning and characterization of the Bacillus sphaericus genes controlling the bioconversion of pimelate into dethiobiotin. AB - Using 8.8 kb of genetic information from Bacillus sphaericus, it was possible to confer to Escherichia coli bio- strains, including delta bioA-D, bioC-, bioH-, the ability to convert exogenous pimelate into biotin. The bio genes were borne on two recombinant plasmids with inserts of 4.3 kb and 4.5 kb, which had been isolated from a genomic bank of HindIII-digested B. sphaericus DNA, by phenotypic complementation of various E. coli bio mutants. The B. sphaericus bioD and bioA genes were unambiguously identified within the 4.3-kb insert and shown to be closely linked to bioY (coding for a protein with a presently unknown function) and to bioB [Ohsawa et al., Gene 80 (1989) 39-48]. These genes are clustered in the order bioDAYB. The 4.5-kb fragment contains genetic information for three different proteins, the products of bioX, bioW and bioF. Complementation studies using an E. coli bioF mutant and a B. subtilis bio112TG3 strain, revealed that the third ORF of this cluster encodes 7-keto-8-aminopelargonic acid synthetase. A combination of bioW and bioF allows an efficient complementation of E. coli bioC and bioH mutants, provided that pimelate is added to the biotin-depleted growth medium. No function could be identified for the product of bioX. The gene order of this cluster is bioXWF. By sequence analysis, the two cloned DNA fragments were shown to bear overlapping open reading frames and secondary structures at their 3' ends, typical of transcription terminators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110101 TI - Physical characterisation of the replication region of the Streptococcus faecalis plasmid pAM beta 1. AB - The complete nucleotide (nt) sequence of a 5.1-kb EcoRI DNA restriction fragment carrying the replication region of the Streptococcus faecalis plasmid pAM beta 1 has been determined. Of the seven major open reading frames (ORF A-G) identified within this fragment, two (C and E) were shown to be encoding by in vitro transcription/translation assays. Evidence was obtained that synthesis of the polypeptide (Mr 57,380) encoded by the largest ORF (E) was essential for replication. Deletion analysis indicated that the minimum unit of DNA required for replication resided on a 2.59-kb AccI-HpaI subfragment. ORF C resided outside of this fragment and encompassed an extensive region of directly repeated nt sequence. The encoded polypeptide (Mr 30,471) was therefore composed of large tracts of reiterated amino acid sequence (11 x VDP and 35 x TEP tripeptides) which probably caused the observed anomalous electrophoretic mobility of the synthesised protein (equivalent to 61 kDa). Deletion of a 416-bp segment of DNA between unique KpnI and StyI sites caused an increase in copy number, which correlated with the in vitro production of higher levels of ORF E polypeptide. Although homology was detected between the sequenced DNA, and the replicon of a closely related streptococcal plasmid (pSM19035), none was evident to any other characterised Gram+ plasmid. PMID- 2110102 TI - Prevalence of novel repeat sequences in and around the P1 operon in the genome of Mycoplasma pneumoniae. AB - The presence of numerous different repetitive elements in the genome of Mycoplasma pneumoniae has been documented by several laboratories. One which we previously identified, denoted as SDC1, has now been further characterized, verified to be distinct from those discussed in previous publications and shown to lack homology to several other species of Mycoplasma when tested under our stringency conditions. As many as eight versions of the SDC1-type repeat, which is more than 400 bp long, are scattered throughout the genome of M. pneumoniae. The prototype for SDC1 is found within a gene encoding a putative 130-kDa membrane-binding protein lying just downstream from the gene encoding the cytadhesin protein P1. In fact, all of the reported M. pneumoniae repetitive elements have at least one representative either within or adjacent to the P1 operon; many if not all of these lie within open reading frames. The function of these repetitive elements is still unclear. PMID- 2110103 TI - Expression of heterobispecific antibodies by genes transfected into producer hybridoma cells. AB - We report the expression of heterobispecific antibodies (Ab) by transferred genes. The kappa and gamma 1 genes of a mouse anti-idiotypic Ab (IgG1) were transfected into a mouse hybridoma cell line secreting Ab (IgG1), directed against an isoenzyme of human creatine kinase. Stable cell lines secreting the parental Ab derived from the introduced genes and a mixture of hybrid Ab were established. The transfected Ab specificity was expressed at similar levels as in a nonproducer background (50 ng-1 microgram/ml), heterobispecific Ab was expressed in microgram quantities (1-4 micrograms/ml) in all cell lines examined. As shown by isoelectric focusing analysis, hybrid Ab (heterobifunctional and other species) are expressed to a similar extent in the transfected cell lines as the Ab in the parental Ab-producing cells. PMID- 2110104 TI - Sequence similarities among monkey ori-enriched (ors) fragments. AB - Nucleotide sequences have been determined for eight ors (ori-enriched sequence) fragments isolated from monkey DNA by a method that was designed to enrich for origins of DNA replication [Kaufmann et al., Mol. Cell. Biol. 5 (1985) 721-727]. Evidence has been presented that some or possibly all of these sequences can serve, albeit inefficiently, as oris in vivo [Frappier and Zannis-Hadjopoulos, Proc. Natl. Acad. Sci. USA 84 (1987) 6668-6672]. Two of the fragments were found to contain the long terminal repeat-like elements of the 'O-family' of moderately repetitive sequences that are present in human DNA as a transposon-like element [Paulson et al., Nature 315 (1985) 359-361]. Extensive pair-wise comparisons of the sequences failed to detect any statistically significant common sequences, except for long asymmetrically distributed A + T-rich stretches. Nonetheless, when the ors fragments were examined for the presence of published consensus sequences, seven of eight were found to contain the control sequence described by Dierks et al. [Cell 32 (1983) 695-706], and the same seven of eight were found to contain both the scaffold attachment region T consensus [Gasser and Laemmli, Cell 46 (1986) 521-530] and the minimal Saccharomyces cerevisiae autonomously replicating sequence consensus [e.g., Palzkill and Newlon, Cell 53 (1988) 441 450]. PMID- 2110105 TI - Genomic organization of the human amyloid beta-protein precursor gene. AB - Amyloid beta-protein (BP) deposited in Alzheimer brains is a cleavage product of a larger precursor (BPP). The BPP gene encodes three types of mRNA generated by alternative splicing, two of which contain the sequence encoding Kunitz-type serine-protease inhibitor (serpin). To investigate the regulatory mechanisms of BPP synthesis at the gene level, we isolated 36 genomic DNA clones covering all the exons of the human BPP gene. This gene consists of 18 exons and spans more than 170 kb. BP is encoded by the 16th and the 17th exons and the serpin domain by the 7th exon. Sequence analysis showed that the 7th and 8th introns lack a typical branchpoint for splicing. This might relate to the alternative splicing. The promoter of the BPP gene has some characteristics of those of housekeeping genes and contains a number of possible methylation sites. The methylation status of the promoter was analyzed by Southern blotting but no alteration was observed among tissues and between control and Alzheimer brains. We also tested the roles of two possible activator protein-1-binding sites and a possible heat-shock element found within the promoter. Northern blotting showed that the transcription of the BPP gene was apparently induced by 12-O-tetradecanoylphorbol 13-acetate (phorbol derivative) in HeLa cells. PMID- 2110106 TI - Long-term care: planting the seed. PMID- 2110107 TI - [Blood thyroid hormone levels and their reaction to thyroliberin in vibration induced pathology]. PMID- 2110108 TI - Microsomal lipid peroxidation: the role of NADPH--cytochrome P450 reductase and cytochrome P450. AB - The role of NADPH--cytochrome P450 reductase and cytochrome P450 in NADPH- and ADP--Fe3(+)-dependent lipid peroxidation was investigated by using the purified enzymes and liposomes prepared from either total rat-liver phospholipids or a mixture of bovine phosphatidyl choline and phosphatidyl ethanolamine (PC/PE liposomes). The results suggest that NADPH- and ADP--Fe3(+)-dependent lipid peroxidation involves both NADPH--cytochrome P450 reductase and cytochrome P450. Just as in the case of cytochrome P450-linked monooxygenations, the role of these enzymes in lipid peroxidation may be to provide two electrons for O2 reduction. The first electron is used for reduction of ADP--Fe3+ and subsequent addition of O2 to the perferryl radical (ADP--Fe3(+)-O2-), which then extracts an H atom from a polyunsaturated lipid (LH) giving rise to a free radical (LH.) that reacts with O2 yielding a peroxide free radical (LOO.). The second electron is then used to reduce LOO. to the lipid hydroperoxide (LOOH). In the latter capacity, reduced cytochrome P450 can be replaced by EDTA--Fe2+ or by the superoxide radical as generated through redox cycling of a quinone such as menadione. PMID- 2110109 TI - The hydroxylation of the salicylate anion by a Fenton reaction and T-radiolysis: a consideration of the respective mechanisms. AB - The yield of 2,3- and 2,5-dihydroxybenzoates (dHB's) from the reaction of .OH radicals with salicylate (SA) ions has been measured as a function of pH and in the presence of oxidants. Under steady-state radiolysis conditions, the production of these products occurs via the reactions .OH + SA----HO-SA. (radical adduct) HO-SA. H+.OH+----2-carboxyphenoxyl radical (SA.) + H2O HO-SA. + SA.--- 2,3-/2,5-dHB + SA The addition of the oxidants O2, Fe3+ edta, or Fe(CN)63- increases the relative yield of 2,5-dHB/2,3-dHB from about 0.2 to 1. A model to account for this effect is presented. Steady-state radiolyses of 3- and 4 hydroxybenzoate give dihydroxybenzoate products consistent with the phenol group being an ortho-para director in the electrophilic attack of the hydroxyl radical on the aromatic ring. A comparison of product distributions from the reaction of ferrous edta with hydrogen peroxide using salicylate as a scavenger strongly suggests that the same hydroxyl radical adducts are formed as in the radiation experiments. PMID- 2110110 TI - Development and validation of a level-of-care instrument for predicting residential placement. AB - A level-of-care instrument developed in Missouri uses discriminant analysis and a criterion measure based on the state's continuum of community residential facilities to assess psychiatric patients' abilities and deficits and to match individual patients with a suitable community setting. The instrument assigned 57 percent of the patients in the sample used in development of the instrument and 43 percent in a validation sample to the same type of residential facility recommended by case managers. The instrument more accurately predicted placement than two instruments that were used earlier in the state and were not based on its specific array of facilities. PMID- 2110111 TI - Discharge and retention of psychogeriatric long-stay patients in a state mental hospital. PMID- 2110112 TI - Data-based interventions to reduce assaults by geriatric inpatients. PMID- 2110114 TI - The endothelium. Target and promoter of hypertension? PMID- 2110115 TI - Recurrent Listeria monocytogenes bacteraemia in a liver transplant patient. AB - We report a case of a recurrent Listeria monocytogenes bacteraemia in a 46 year old liver transplant patient. Serotyping revealed that the two episodes of bacteraemia were caused by different strains. The possibility of a recrudescence of a persisting infection was rejected. We concluded that the recurrent bacteraemia in this predisposed patient was due to re-infection, and that antibiotic treatment (amoxicillin plus an aminoglycoside) resulted in a complete eradication of the infective microorganism. Therefore long-term suppressive antibiotic treatment was not indicated. The source of these L. monocytogenes infections was not found. PMID- 2110113 TI - Prostacyclin and thromboxane biosynthesis in mild essential hypertension. AB - The possibility that prostacyclin or thromboxane biosynthesis is abnormal in patients with established mild essential hypertension was investigated in 46 patients. These eicosanoids have opposing effects both on vascular smooth muscle and on platelets. An imbalance in their biosynthesis could therefore influence both vascular tone and predisposition to thrombosis. We studied the relation between blood pressure and the biosynthesis of prostacyclin and thromboxane A2 by measuring urinary excretion rates of stable breakdown products of prostacyclin (6 oxo-prostaglandin F1 alpha and 2,3-dinor-6-oxo-prostaglandin F1 alpha) and of thromboxane A2 (thromboxane B2 and 2,3-dinor-thromboxane B2) using immunoaffinity chromatography and gas chromatography/electron capture mass spectrometry. Excretion rates of both of the prostacyclin-derived products ranged from less than 5 to more than 100 ng/g creatinine; each was significantly negatively correlated with blood pressure (r = 0.36-0.45). A reduction of 2,3-dinor-6-oxo prostaglandin F1 alpha excretion of 100 ng/g creatinine was associated with an increase in arterial pressure of 14 mm Hg (systolic) and 8 mm Hg (diastolic) in patients who had been without antihypertensive medication for 2 weeks. The same reduction in 6-oxo-prostaglandin F1 alpha excretion was associated with an increased pressure of 19 mm Hg (systolic) and 12 mm Hg (diastolic) (2p less than 0.05 for diastolic pressure and 2p less than 0.01 for systolic pressure in each case). There were similar correlations between the excretion rates of these products and blood pressure in the same patients while they were receiving antihypertensive therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110116 TI - Gram-positive bacterial sepsis in rat and tissue lipolytic activity on commercial parenteral fat emulsions. AB - To study the influence of a gram-positive sepsis on the metabolism of circulating lipids, fasted rats were injected with saline (control group) or with a suspension of heat-killed or live Staphylococcus aureus. 18 h later, body temperature was increased, while albuminemia and ketonemia were decreased in the group injected with heat-killed bacteria, as opposed to the control group. Passing from these groups to the group injected with live bacteria, more differences appeared: increase of triglyceridemia and free cholesterolemia; decrease of esterified cholesterol levels and especially of the in vitro activity of diaphragm, heart and adipose tissue lipoprotein lipase and of hepatic lipase. The decrease of lipolytic activities occurred whether they were measured on a fat emulsion containing long-chain or medium- and long-chain triglycerides. The fact that for the latter the activity was always higher than for the former suggests that the host infected with gram-positive bacteria would clear exogenous fat more easily in the case of medium-chain triglycerides. PMID- 2110117 TI - Correlation of hepatitis C virus antibodies with HIV-1 seropositivity in intravenous drug addicts. PMID- 2110118 TI - Listeria isolations from feces of patients with diarrhea and from healthy food handlers. AB - A study was undertaken on the presence and frequency of Listeria sp. in feces from 1,000 patients suffering from diarrheal diseases and from 2,000 healthy persons. Furthermore, the feces of patients were examined for other well documented enteropathogens such as Campylobacter, Salmonella, Shigella, Staphylococcus aureus, Yersinia enterocolitica, protozoa and rotavirus as well as for organisms of questionable enteropathogenic potency such as fungi, i.e. Candida. Finally, in continuation of previously described investigations of the enteropathogenic role of Proteus mirabilis but not of Proteus vulgaris, both these species were studied too. Only Listeria innocua and Listeria monocytogenes could be detected in the investigated fecal specimens. There were no differences of the frequencies of L. innocua, and L. monocytogenes between patients and healthy persons. 17 strains (= 1.7%) of L. innocua and six strains (= 0.6%) of L. monocytogenes were isolated from 1,000 samples of patients. As a comparison 2,000 fecal samples from healthy people contained 40 strains (= 2.0%) of L. innocua and 16 strains (= 0.8%) of L. monocytogenes. A coincidence study showed that there were no statistically significant correlations between well-known enteropathogens and Listeria sp., Proteus sp. or any of the other isolates. Significant correlations were found only between harmless species such as L. innocua and P. vulgaris. PMID- 2110119 TI - Excystation of five digenean metacercariae in vitro and in the peritoneal cavity of the mouse. AB - Excystation of metacercariae of Parorchis acanthus, Posthodiplostomum nanum, Posthodiplostomum sp., Posthodiplostomoides leonensis and Clinostomum tilapiae in mammalian saline at 39 degrees C was similar to their excystation in mouse peritoneal cavity. Extrinsic enzymes were not needed for C. tilapiae excystation but were an absolute necessity for P. acanthus excystation. Extrinsic pepsin enhanced P. nanum excystation but was not obligatory. Acid pepsin was an absolute requirement for Posthodiplostomum sp. and Posthodiplostomoides leonensis excystation. It was noted that acid saline could not be substituted for acid pepsin and that there was diversity in the condition involved in digenean excystation. PMID- 2110120 TI - The effects of radiographic contrast media on myocardial contractility and coronary resistance: osmolality, ionic concentration, and viscosity. AB - With the ongoing development of new contrast agents, questions develop concerning the cardiac effects of these drugs. We used the perfused rat heart model to investigate the effects on cardiac and coronary function of hypertonic ionic (sodium chloride) and nonionic (glucose) solutions and conventional and low osmolality radiographic contrast media (RCM). We also evaluated the concurrent effects of RCM on prostacyclin and adenine nucleotide/nucleoside release. Hypertonic solutions of glucose had little effect on myocardial contraction (increase up to 7.7 +/- 0.9%), while NaCl solutions of similar osmolality were negatively inotropic (contractile force decreased up to 76.1 +/- 9.2%). Conventional RCM were negatively inotropic (decrease of 59.6 +/- 5.6% with Conray (Mallinckrodt Pharmaceuticals, St. Louis, MO), 32.2 +/- 3.2% with Angiovist 282 (Berlex Laboratories, Cedar Knolls, NJ]; two nonionic RCM, Iopamidol and Iotrol had little effect on myocardial contraction (reduction of 6.9 +/- 1.4% and increase of 12.0 +/- 2.9%, respectively). Hypertonic solutions of glucose and NaCl reduced coronary resistance in direct relationship to hyperosmolality. Conventional RCM also reduced coronary resistance, while the nonionic media caused minor alteration. None of the solutions tested altered prostacyclin or adenine nucleotide/nucleoside efflux from the heart. A solution of Ficoll 70 with a viscosity similar to that of RCM increased myocardial contraction by 9.6 +/- 3.6% and had no effect on coronary resistance, indicating that viscosity per se did not contribute to the negative inotropic effects or the reduction in coronary resistance. Hypertonic solutions, including conventional RCM, reduce coronary resistance as a result of their hyperosmolality Negative inotropic effects, however, are more related to high ionic concentration than to osmolality. PMID- 2110122 TI - The chief scientist reports ... using economic appraisal in health services research. PMID- 2110121 TI - Late onset globoid leukodystrophy: unusual clinical and CSF findings. AB - During a febrile upper respiratory tract illness this 4 year old boy developed left hemiparesis, which progressed to loss of walking and even of sitting finally to tetraplegia. The cerebrospinal fluid protein pattern showed blood-brain barrier damage with additional intrathecal IgG synthesis. The symptoms responded to steroid therapy but resumed and worsened on withdrawal. Only late, when visual evoked potentials and nerve conduction velocity proved to be impaired, was Krabbe disease diagnosed on the assay of cultured fibroblasts for galactocerebroside beta-galactosidase. We discuss the significance of possible endogenous production of IgG in the CNS. PMID- 2110123 TI - Herd benefit-to-cost ratio and effects of a bovine mastitis control program that includes blitz treatment of Streptococcus agalactiae. AB - Twelve dairy herds that had participated in the Pennsylvania Dairy Herd Improvement Association (DHIA) program for at least 12 months, that had a 12 month mean DHIA somatic cell count greater than 700,000 cells/ml, and that had greater than 25% of lactating cows infected with Streptococcus agalactiae participated in a herd blitz treatment program. Initially, quarter milk samples for bacteriologic culturing were collected from all lactating cows. Subsequently, all cows identified as infected with Str agalactiae were treated, using a commercial penicillin-novobiocin intramammary infusion product. In addition, a herd mastitis management program of postmilking teat dipping and treatment of all cows at the start of the nonlactating period was instituted. Thirty days after the initial herd visit, samples from all lactating cows were again cultured, and cows infected at that time were treated. Twelve months after the initial herd visit, samples from all lactating cows were again cultured. Mean prevalence of infection with Str agalactiae decreased (P less than 0.05) from 23.0% of quarters and 41.6% of cows initially to 3.4% of quarters and 9.3% of cows at 30 days and 1.6% of quarters and 4.2% of cows at 1 year. Mean herd DHIA somatic cell count decreased (P less than 0.05) from 918,000 cells/ml initially to 439,000 cells/ml at 30 days and 268,000 cells/ml at 1 year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110125 TI - Sunlight, DNA damage and skin cancer: a new perspective. PMID- 2110124 TI - Decreased colostral immunoglobulin absorption in calves with postnatal respiratory acidosis. AB - The effect of postnatal acid-base status on the absorption of colostral immunoglobulins by calves was examined in 2 field studies. In study 1, blood pH at 2 and 4 hours after birth was related to serum IgG1 concentration 12 hours after colostrum feeding (P less than 0.05). Decreased IgG1 absorption from colostrum was associated with respiratory, rather than metabolic, acidosis, because blood PCO2 at 2 and 4 hours after birth was negatively related to IgG1 absorption (P less than 0.05), whereas serum bicarbonate concentration was not significantly related to IgG1 absorption. Acidosis was frequently observed in the 30 calves of study 1. At birth, all calves had venous PCO2 value greater than or equal to 60 mm of Hg, 20 of the calves had blood pH less than 7.20, and 8 of the calves had blood bicarbonate concentration less than 24 mEq/L. Blood pH values were considerably improved by 4 hours after birth; only 7 calves had blood pH values less than 7.20. Calves lacking risk factors for acidosis were examined in study 2, and blood pH values at 4 hours after birth ranged from 7.25 to 7.39. Blood pH was unrelated to IgG1 absorption in the calves of study 2. However, blood PCO2 was again found to be negatively related to colostral IgG1 absorption (P less than 0.005). Results indicate that postnatal respiratory acidosis in calves can adversely affect colostral immunoglobulin absorption, despite adequate colostrum intake early in the absorptive period. PMID- 2110126 TI - Etoposide protects mice from radiation-induced bone marrow death. AB - Etoposide is known to inhibit the activity of topoisomerase II, and to possess radiosensitizing effects. In this paper we show that pretreatment of mice with etoposide one day before whole-body irradiation had a protective effect against radiation-induced bone marrow death. The LD50/30 of mice given radiation alone was 8.26 Gy while that of mice given etoposide one day before whole-body irradiation was 10.35 Gy. The number of endogenous colony-forming units surviving in whole body-irradiated mice was significantly increased by pretreatment with etoposide. PMID- 2110127 TI - A case-control study of male colorectal cancer in Aichi Prefecture, Japan: with special reference to occupational activity level, drinking habits and family history. AB - The relationships of occupational activity level, drinking habits and family history of cancer to the risk of male colorectal cancer by subsites were investigated in a case-control study involving 1,716 cases with colon cancer, 1,611 cases with rectal cancer and 16,600 controls with other sites of cancer identified from the Aichi Cancer Registry, Japan 1979-1987. An occupation with a low activity level was associated with an increased risk of colorectal cancer; the age-adjusted relative risk (RR) compared to the high activity level group was 1.92 (95% confidence interval (CI): 1.38-2.67) for proximal colon cancer, 1.52 (95% CI: 1.19-1.94) for distal colon cancer and 1.38 (95% CI: 1.17-1.62) for rectal cancer. Beer drinkers showed an increased risk of colorectal cancer; the age-adjusted RR was 1.49 (95% CI: 1.13-1.95) for proximal colon cancer, 1.65 (95% CI: 1.34-2.04) for distal colon cancer and 1.88 (95% CI: 1.62-2.18) for rectal cancer. The RR for family history of colorectal cancer was 3.40 (95% CI: 2.19 5.29) for proximal colon cancer, 2.54 (95% CI: 1.73-3.75) for distal colon cancer and 1.78 (95% CI: 1.28-2.49) for rectal cancer. Multivariate analysis controlled for age, residence, marital status and smoking in addition to occupational activity level, beer drinking and family history of colorectal cancer did not materially change the RRs. When these three variables were combined, the RR was 15.72 (95% CI: 5.40-45.78) for proximal colon cancer, 10.55 (95% CI: 4.24-26.27) for distal colon cancer and 6.69 (95% CI: 3.12-14.36) for rectal cancer. PMID- 2110128 TI - Lack of tumorigenicity of aminopyrine orally administered to B6C3F1 mice. AB - To test the tumorigenic potential of aminopyrine, an antipyretic analgesic, it was administered in drinking water at levels of 0 (control), 0.04 and 0.08% to 50 male and 50 female B6C3F1 mice for 100 weeks, and the mice were subsequently maintained without aminopyrine for a further 4 weeks. The most frequent types of tumor, in both treated and control groups, were hepatocellular tumor in male mice and malignant lymphoma/lymphoid leukemia in female mice. No statistically significant differences were observed in the incidences of these tumors between treated and control groups. The incidences of several other tumors in male and female mice also showed no statistically significant differences between treated and control groups. Therefore, no tumorigenic effect of orally administered aminopyrine in B6C3F1 mice was apparent in the present study. PMID- 2110129 TI - Effects of a choline-deficient diet and a hypolipidemic agent on single glutathione S-transferase placental form-positive hepatocytes in rat liver. AB - Using the placental form of glutathione S-transferase (GST-P) as a marker of carcinogen-initiated hepatocytes, we investigated how a choline-deficient (CD) diet and BR931, a carcinogenic hypolipidemic agent, modify populations of single GST-P-positive hepatocytes. The liver of male Fischer rats (6-7 weeks old) fed a CS or basal diet contained mostly single or double GST-P-positive hepatocytes. Feeding a CD diet for 2-4 weeks led to increases in the number of aggregates of two and three GST-P-positive hepatocytes. By 8-12 weeks, there was an emergence of discrete foci of GST-P-positive hepatocytes consisting of more than 20 hepatocytes. Feeding a BR931 diet for 4-8 weeks resulted in no significant change in the number of single GST-P-positive hepatocytes in the liver as compared to feeding a basal diet. It is suggested that single GST-P-positive hepatocytes in the liver of relatively young rats maintained on a commercial diet may represent endogenously initiated cells. A CD diet promotes endogenously initiated cells to form larger aggregates or foci of GST-P-positive cells. PMID- 2110130 TI - Frequent glycine-to-aspartic acid mutations at codon 12 of c-Ki-ras gene in human pancreatic cancer in Japanese. AB - Point mutations at codons 12 and 13 of c-Ki-ras gene were analyzed in human pancreatic cancer. DNAs obtained from sample tissues were amplified by means of polymerase chain reaction and were analyzed by dot blot hybridization assays with oligonucleotide probes appropriate for detecting mutations at these codons. Out of 38 evaluated cases, point mutations at codon 12 were found in 35 cases; these mutations resulted in changes of the coded amino acid to aspartic acid in 24 cases, to valine in 9 cases, to arginine in 2 cases and to cysteine in one case. In one case, a glycine-to-aspartic acid mutation was found at codon 13. In two cases, two distinct mutations were simultaneously present. The frequency pattern of mutations at codon 12 was somewhat different from those given in two previous reports on the similar analysis of pancreatic cancers in European countries. This may indicate the presence of possible genetic or non-genetic factors in determining preferential mutational patterns at these particular codons. PMID- 2110131 TI - Analysis of clonal evolution in a tumor consisting of pSV2neo-transfected mouse fibrosarcoma clones. AB - The process of clonal evolution was analyzed in a line of methylcholanthrene induced mouse fibrosarcomas. The tumor cells were transfected with pSV2neo gene and 22 clones were randomly isolated. Genetically tagged clones were mixed and inoculated into syngeneic mice. Southern blot analysis revealed that one of the clones, no. 11, dominated both in tumors in situ and in lung metastatic nodules. No. 11 clone and other clones were similar in growth rates in vitro and in vivo, in spontaneous and experimental metastatic abilities, in immunogenicity, and in the capacity of intercellular communication in vitro. Although no. 11 clone overgrew other clones in vivo, this was not the case when clones were mixed and maintained in vitro. We conclude that clonal interactions in vivo may be responsible for the dominance of no. 11 clone in the tumor. It is likely that the preferential metastasis of no. 11 clone to the lung may be a simple reflection of the proliferative advantage of the dominant clone in the tumor in situ. PMID- 2110132 TI - Chromosome abnormalities of gastric cancer detected in cancerous effusions. AB - The chromosomes were examined in cancerous effusions obtained from 7 patients with gastric cancer. In 1 patient, the modal chromosome number was 46 with a normal chromosome complement in the majority of the cells examined. The other 6 patients revealed numerical and structural aberrations. Among the structural rearrangements detected, chromosome 3 was involved in the short arm and in the long arm, each in three patients; bands p25, q21, q23, and q27 were recurrently involved and a band q23 was lost in 3 patients. Rearrangements of chromosome 5 in the long arm and of chromosome 17 at or near the centromere were also observed in three patients each. Gains of chromosome 7 was seen in 5 patients and of chromosome 13 in 4. Some of these alterations may be specific for gastric cancer. PMID- 2110133 TI - Evaluation of mizoribine as an immunosuppressant in subrenal capsule assay using immunocompetent mice. AB - We studied the application of mizoribine (MZR) to normal immunocompetent mice in subrenal capsule assay (SRCA) by means of tumor growth curve determination, histological analysis and autoradiography. At 400 mg/kg, MZR prolonged the actual tumor growth and moderately reduced the host reaction. Doses below 200 mg/kg did not effectively suppress the host reaction. The maximal weight loss of mice in the 400 mg/kg group reached 29%, but did not exceed 10% within 8 days. Hence, we applied 400 mg/kg of MZR to SRCA for up to eight days for cancer chemotherapy testing. This dose of MZR did not affect the labeling index of tumor cells compared with the control. PMID- 2110134 TI - Prediction from creatinine clearance of thrombocytopenia and recommended dose in patients receiving (glycolato-O,O')-diammine platinum (II) (NSC 375101D). AB - Thrombocytopenia is the most serious dose-limiting toxicity of (glycolato-O,O') diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues. A total of 38 patients treated with 100 mg of 254-S per m2 in a clinical phase II study were retrospectively analyzed to determine the factors influencing thrombocytopenia. Performance status, sex, age and prior chemotherapy did not affect either the percent reduction of platelets or the nadir platelet count. However, creatinine clearance (Ccr.: ml/min) was found to be a predictive variable for thrombocytopenia. There was a significant relationship between nadir platelet count and Ccr. (R2 = 0.637) or relative dose [RD = (dose of 254-S: mg/m2)/Ccr.] (R2 = 0.707). From these observations, the following equations for predicting nadir platelet count associated with administration of 254-S were proposed. [Nadir platelet count] = -64,264.7 + 2,783.4 x [Ccr.] (A) log [Nadir platelet count] = -1.6743 log [RD] + 5.32 = -1.6743 log [Dose/Ccr.] + 5.32 (B) If we administer 100 mg of 254-S per m2 to a patient with Ccr. of less than 40.3 ml/min, thrombocytopenia of grade 3 or more according to the Eastern Cooperative Oncology Group (ECOG) criteria (less than 50,000/mm3) can be predicted from equation (A). In these patients, dose modification using equation (B) is recommended. PMID- 2110135 TI - Multiple primary cancer: the U.S.-Japan Cooperative Cancer Research Program. PMID- 2110136 TI - The 42- and 51-kilodalton mosquitocidal proteins of Bacillus sphaericus 2362: construction of recombinants with enhanced expression and in vivo studies of processing and toxicity. AB - After site-directed mutagenesis, the genes coding for the 42- and 51-kilodalton (kDa) mosquitocidal proteins of Bacillus sphaericus 2362 were placed under the regulation of the aprE (subtilisin) promoter of the Bacillus subtilis vector pUE (a derivative of pUB18). The levels of expression of the gene products in B. subtilis DB104 and B. sphaericus 718 were assessed by bioassays with larvae of Culex pipiens and by Western immunoblots. The results indicated that a higher amount of protein was produced in B. subtilis DB104. Electron microscopic examination of B. subtilis DB104 and B. sphaericus 718 containing the 42- and 51 kDa proteins indicated that amorphous inclusions accumulated in the former species and that crystals identical in appearance to that found in B. sphaericus 2362 were produced in the latter. Strains producing only the 42- or the 51-kDa protein were not toxic to larvae of C. pipiens. A mixture of both strains, a single strain producing both proteins, or a fusion of the 51- and the 42-kDa proteins was toxic. The amount of B. subtilis DB104 containing the 42- and the 51 kDa proteins necessary to kill 50% of the larvae of C. pipiens was 5.6 ng (dry weight) of cells per ml. This value was significantly lower than that for B. sphaericus 2362 (14 ng [dry weight] per ml). Larvae consuming purified amorphous inclusions containing the 42-kDa protein degraded this protein this protein to primarily 39- and 24-kDa peptides, whereas inclusions with the 51-kDa protein were primarily degraded to a protein of 44 kDa. Past studies involving purified proteins from B. sphaericus 2362 indicate an associate of toxicity with the 39 kDa peptide. The results presented here suggest that the 44-kDa degradation product of the 51-kDa protein may also be required for toxicity. PMID- 2110137 TI - Purification and characterization of an active fragment of the LasA protein from Pseudomonas aeruginosa: enhancement of elastase activity. AB - A 22-kilodalton protein purified from the culture supernatant fraction of Pseudomonas aeruginosa (strains PA220 and PAO1) was found to enhance the elastolytic activity of purified P. aeruginosa elastase. N-terminal sequence analysis identified the protein as a fragment of the lasA gene product (P.A. Schad and B.H. Iglewski, J. Bacteriol. 170:2784-2789, 1988). However, comparative analysis with the reported LasA sequence indicated that the purified LasA fragment is longer than the deduced sequence reported. The purified LasA fragment had minimal elastolytic and proteolytic activity and did not enhance the proteolytic activity of purified elastase, yet enhanced the elastolytic activity more than 25-fold. The LasA fragment was found to also enhance the elastolytic activities of thermolysin, human neutrophil elastase, and proteinase K. The results presented here suggest that the LasA protein interacts with the elastin substrate rather than modifying elastase. PMID- 2110139 TI - Relationship between DNA cycle and growth rate in Synechococcus sp. strain PCC 6301. AB - Flow cytometry was used to examine cell cycle regulation in Synechococcus sp. strain PCC 6301 under a variety of growth conditions. The DNA frequency distributions of exponentially growing and dark-blocked populations confirmed that this cyanobacterium contains multiple chromosome copies even at very slow growth rates. Furthermore, the presence of major peaks corresponding to other than 2" chromosome copies strongly suggests that DNA replication is initiated asynchronously. Although this suggestion is at odds with the standard formulation of the procaryotic cell cycle model, it is similar to recent observations of asynchrony in Escherichia coli replication mutants. PMID- 2110140 TI - Expression and regulation of glucoamylase from the yeast Schwanniomyces castellii. AB - Expression of the 146-kilodalton (kDa) extracellular glucoamylase by the budding yeast Schwanniomyces castellii is induced by maltose and starch. By use of antiglucoamylase antisera, we found that this expression was regulated at the level of the mRNA, taking place within 30 min after exposure of yeast cells to the respective sugars. Polyacrylamide gel electrophoresis analysis of the in vitro-translated products of total RNA from maltose-treated cells established that the glucoamylase precursor was approximately 120 kDa in size. Stable glucoamylase transcript was not produced in cells exposed to glucose, 2 deoxyglucose, and heat shock. Cells exposed to these two sugars also degraded intracellular and extracellular glucoamylase. In the presence of sugars such as cellobiose, galactose, lactose, and xylose or in the absence of any carbohydrate, a low-level, constitutive-like expression of this preglucoamylase occurred. The nascent glucoamylase underwent at least two posttranslational modifications, resulting in a 138-kDa cell-associated form and the 146-kDa active form that was found free in the medium. These results suggest that glucoamylase expression is tightly regulated similarly to expression of the enzymes responsible for maltose metabolism in Saccharomyces yeasts. PMID- 2110138 TI - Cloning and characterization of the hemA region of the Bacillus subtilis chromosome. AB - A 3.8-kilobase DNA fragment from Bacillus subtilis containing the hemA gene has been cloned and sequenced. Four open reading frames were identified. The first is hemA, encoding a protein of 50.8 kilodaltons. The primary defect of a B. subtilis 5-aminolevulinic acid-requiring mutant was identified as a cysteine-to-tyrosine substitution in the HemA protein. The predicted amino acid sequence of the B. subtilis HemA protein showed 34% identity with the Escherichia coli HemA protein, which is known to code for the NAD(P)H:glutamyl-tRNA reductase of the C5 pathway for 5-aminolevulinic acid synthesis. The B. subtilis HemA protein also complements the defect of an E. coli hemA mutant. The second open reading frame in the cloned fragment, called ORF2, codes for a protein of about 30 kilodaltons with unknown function. It is not the proposed hemB gene product porphobilinogen synthase. The third open reading frame is hemC, coding for porphobilinogen deaminase. The fourth open reading frame extends past the sequenced fragment and may be identical to hemD, coding for uroporphyrinogen III cosynthase. Analysis of deletion mutants of the hemA region suggests that (at least) hemA, ORF2, and hemC may be part of an operon. PMID- 2110141 TI - The genes for three xylan-degrading activities from Bacteroides ovatus are clustered in a 3.8-kilobase region. AB - Genes coding for three xylan-degrading activities, xylanase, xylosidase, and arabinosidase, were simultaneously cloned from the colonic anaerobic organism Bacteriodes ovatus. The genes for the three enzymes were located on a 3.8 kilobase EcoRI genomic insert and were cloned by using plasmid pUC18. All three activities were expressed in Escherichia coli JM83, and all were cell associated. Expression of the xylanase gene was independent from expression of the xylosidase and arabinosidase genes, whereas expression of the latter two genes appeared to be coordinated. Restriction endonuclease analysis of the arabinosidase and xylosidase genes and partial purification of these enzyme activities from E. coli suggested that these activities were catalyzed by a bifunctional protein or two proteins of very similar molecular weight. All three enzyme activities were regulated in B. ovatus in response to the carbon source used for growth. This is the first report of the cloning and expression of B. ovatus genes. PMID- 2110142 TI - Identification and characterization of a new replication region in the Neisseria gonorrhoeae beta-lactamase plasmid pFA3. AB - The 7.1-kilobase-pair (kbp) plasmid pFA3 specifies TEM beta-lactamase production in Neisseria gonorrhoeae. We studied the minimal region required for replication of this plasmid in Escherichia coli by constructing a set of nested deletions of the 3.4-kbp PstI-HindIII fragment. The smallest fragment capable of maintenance in E. coli when ligated to a streptomycin-spectinomycin resistance cassette was 2.0 kbp in size and was different from another autonomously replicating fragment of pFA3 reported by K. H. Yeung and J. Dillon (Plasmid 20:232-240, 1988). The fragment contained single BamHI and XbaI sites and specified a 39-K protein. Fragments subcloned from the minimal region or constructed by deletion from the 3' or 5' ends were not capable of autonomous replication. Mutants constructed by end filling and religating DNA cleaved at the BamHI or XbaI sites were not capable of autonomous replication and no longer produced the 39K protein. These results suggest that replication is dependent on the 39K protein. DNA sequence analysis of the region showed an A-T-rich region followed by four 22-bp direct repeats followed by an open reading frame encoding a 39K basic protein. PMID- 2110143 TI - A polymerase chain reaction-based approach to cloning sigma factors from eubacteria and its application to the isolation of a sigma-70 homolog from Chlamydia trachomatis. AB - Taking advantage of the known sequence conservation of portions of bacterial sigma factor proteins, we have designed degenerate oligonucleotides corresponding to these domains and used these synthetic DNA sequences as primers in a polymerase chain reaction (PCR) to amplify DNA sequences from the chlamydial genome. The PCR products were used as a probe to recover the genomic fragments from a library of cloned murine Chlamydia trachomatis DNA. Sequence analysis of one of these clones revealed striking homology to the sigma-70 protein of Escherichia coli and the sigma-43 protein of Bacillus subtilis, strongly implying that this locus (sigA) encodes the major vegetative sigma factor of murine C. trachomatis. This PCR-based approach will be broadly applicable to the cloning of major sigma factors from other eubacteria. PMID- 2110144 TI - DNA sequence and expression analysis of algP and algQ, components of the multigene system transcriptionally regulating mucoidy in Pseudomonas aeruginosa: algP contains multiple direct repeats. AB - The complete nucleotide sequence of a 3.2-kilobase-pair chromosomal region containing the algP and algQ genes was determined. The algQ gene encodes an acidic 18-kilodalton polypeptide required for transcriptional activation of the algD gene. The algD gene product catalyzes a critical step in alginate biosynthesis, and its overproduction is necessary for the emergence of mucoid Pseudomonas aeruginosa during chronic infections in cystic fibrosis. A novel genetic element, algP, was identified immediately downstream of algQ. This gene appears to act synergistically with algQ. Unlike a biosynthetic gene, algD, and another regulatory gene, algR, which undergo transcriptional activation in mucoid cells, both algP and algQ are equally transcribed in mucoid and nonmucoid isogenic strains of P. aeruginosa. The promoter regions of algP and algQ were mapped by using S1 nuclease protection analysis. The algQ promoter was also analyzed and showed activity in an in vitro transcriptional runoff assay with major RNA polymerase species from P. aeruginosa and Escherichia coli. The putative algQ and algP promoter sequences, unlike algD and algR, resemble sigma 70-utilized promoters from E. coli and appeared constitutively transcribed at a low level in P. aeruginosa. The algP gene has an unusual DNA sequence, with multiple direct repeats organized in six highly conserved, tandemly arranged, 75 base-pair (bp) units. At a lower level, this sequence had 45 degenerate repeats of 12 bp overlapping with the 75-bp repeats and extending beyond the region of 75 bp repeats. The algP repeats appeared important for the function of the algQ-algP regulatory region in maintaining mucoidy. PMID- 2110145 TI - Sequencing the gene for an imipenem-cefoxitin-hydrolyzing enzyme (CfiA) from Bacteroides fragilis TAL2480 reveals strong similarity between CfiA and Bacillus cereus beta-lactamase II. AB - Using a newly constructed Bacteroides fragilis-Escherichia coli cloning shuttle vector, pJST61, we have cloned the cefoxitin (FOX)-imipenem (IMP) resistance determinant from B. fragilis TAL2480. FOX-IMP resistance in this strain results from the production of a periplasmic, Zn2(+)-containing beta-lactamase which hydrolyzes carbapenems and cephamycins and whose activity is resistant to clavulanic acid but sensitive to Zn2(+)-binding reagents, including EDTA. The pJST61 vector permits efficient library construction in E. coli and allows for the transfer of the library to B. fragilis recipients for the screening or selection of specific phenotypes. The library clone containing the FOX-IMP resistance gene was detected after transfer to B. fragilis TM4000 (Fox-Imps) selecting for Foxr. One of the isolates carrying plasmid pJST241 is resistant to FOX and IMP and synthesizes a periplasmic protein with substrate and inhibitor properties identical to those of strain TAL2480. On the basis of deletion analysis, Tn1000 insertion mutations, and DNA sequencing, we have defined the 747 base cfiA (FOX-IMP resistance) gene within the 3.6-kilobase cloned insert in pJST241. The cfiA gene contains an open reading frame that could code for a precursor protein of 249 amino acids and with a molecular mass of 27,260 daltons. A potential signal sequence has been identified at the N terminus of this protein; cleavage within this sequence would result in a protein of 231 amino acids with a molecular mass of 25,249 daltons. The CfiA protein shows remarkable similarities to the exported, Zn2(+)-requiring, type II beta-lactamase Blm proteins from Bacillus cereus 569/H and 5/B/6. Although overall amino acid identity is only 32%, the Zn ligand-binding His and Cys residues are precisely conserved and the amino acids in the vicinity of these sites show strong similarities (greater than 80%) when the CfiA and Blm proteins are compared. PMID- 2110146 TI - Legionella pneumophila zinc metalloprotease is structurally and functionally homologous to Pseudomonas aeruginosa elastase. AB - The sequence of the structural gene encoding the Legionella pneumophila extracellular zinc metalloprotease has been determined and was found to possess a single large open reading frame (ORF) of 1,629 nucleotides (nt). This ORF was preceded by consensus promoter (TTAACT . . . 17 nt . . . TATAAC) and ribosome binding (TAAGGAG) sequences. The deduced polypeptide contained a putative signal sequence and a total of 543 amino acid residues with a computed molecular size of 60,775 daltons, substantially larger than the observed 38,000 daltons of the native and recombinant proteins. A homology search revealed extensive amino acid identity with Pseudomonas aeruginosa elastase, a protein that is also encoded by an ORF substantially larger than that predicted for the mature size of the protein. The structural identity between the L. pneumophila protease and P. aeruginosa elastase was most pronounced in the regions forming the enzymatic active site of elastase. Amino acid residues constituting the active-site cleft of elastase were greater than 75% conserved. Elastase residues that interact with and mediate proteolysis of substrate peptides were 100% conserved. Competitive inhibitors of elastase and the structurally and functionally related thermolysin (phosphoramidon and a phosphoramidate analog, Z-GlyP(O)Leu-Ala), were shown to be equally potent at inhibiting the proteolytic activity of the L. pneumophila protease. These inhibitor studies along with the amino acid sequence similarities provide strong evidence that the L. pneumophila protease and P. aeruginosa elastase share a similar molecular mechanism of proteolysis. PMID- 2110147 TI - Characterization of PBSX, a defective prophage of Bacillus subtilis. AB - PBSX, a defective Bacillus subtilis prophage, maps to the metA-metC region of the chromosome. DNA (33 kilobases) from this region of the chromosome was cloned and analyzed by insertional mutagenesis with the integrating plasmid pWD3. This plasmid had a promoterless alpha-amylase gene (amyL) that provided information on the direction and level of transcription at the site of integration. Transcription under the control of the PBSX repressor proceeded in the direction metA to metC over a distance of at least 18 kilobases. Electrophoretic analysis of proteins produced by different integrant strains upon PBSX induction and by fragments subcloned in Escherichia coli allowed the identification of early and late regions of the prophage. A set of contiguous fragments directing mutagenic integration suggested that the minimum size of an operon that encodes phage structural proteins is 19 kilobases. The adaptation of PBSX transcriptional and replicational functions to a chromosomally based, thermoinducible expression system is discussed. PMID- 2110148 TI - Isolation and molecular genetic characterization of the Bacillus subtilis gene (infB) encoding protein synthesis initiation factor 2. AB - Western blot (immunoblot) analysis of Bacillus subtilis cell extracts detected two proteins that cross-reacted with monospecific polyclonal antibody raised against Escherichia coli initiation factor 2 alpha (IF2 alpha). Subsequent Southern blot analysis of B. subtilis genomic DNA identified a 1.3-kilobase (kb) HindIII fragment which cross-hybridized with both E. coli and Bacillus stearothermophilus IF2 gene probes. This DNA was cloned from a size-selected B. subtilis plasmid library. The cloned HindIII fragment, which was shown by DNA sequence analysis to encode the N-terminal half of the B. subtilis IF2 protein and 0.2 kb of upstream flanking sequence, was utilized as a homologous probe to clone an overlapping 2.76-kb ClaI chromosomal fragment containing the entire IF2 structural gene. The HindIII fragment was also used as a probe to obtain overlapping clones from a lambda gt11 library which contained additional upstream and downstream flanking sequences. Sequence comparisons between the B. subtilis IF2 gene and the other bacterial homologs from E. coli, B. stearothermophilus, and Streptococcus faecium displayed extensive nucleic acid and protein sequence homologies. The B. subtilis infB gene encodes two proteins, IF2 alpha (78.6 kilodaltons) and IF2 beta (68.2 kilodaltons); both were expressed in B. subtilis and E. coli. These two proteins cross-reacted with antiserum to E. coli IF2 alpha and were able to complement in vivo an E. coli infB gene disruption. Four-factor recombination analysis positioned the infB gene at 145 degrees on the B. subtilis chromosome, between the polC and spcB loci. This location is distinct from those of the other major ribosomal protein and rRNA gene clusters of B. subtilis. PMID- 2110149 TI - Genetic mapping of the obligate methylotroph Methylobacillus flagellatum: characteristics of prime plasmids and mapping of the chromosome in time-of-entry units. AB - A pULB113 (RP4::mini-Mu cts) plasmid was used to generate a library of prime plasmids carrying fragments of the Methylobacillus flagellatum genome. The genes carried by these prime plasmids were identified by complementation after transfer to suitably marked Escherichia coli and Pseudomonas aeruginosa strains. The hybrid plasmids were used for complementation mapping with a range of E. coli, M. flagellatum, and P. aeruginosa mutants. A preliminary map of the M. flagellatum genome section with seven groups of linked markers was obtained. Three of seven groups contain an overlapping sequence of cloned genes and can be considered as one large group of linked genes. A high-frequency-of-recombination donor of M. flagellatum (strain MFK64) mobilized the chromosome in a polarized manner from a single transfer origin. The donor was used to construct a time-of-entry map of the M. flagellatum chromosome. This was achieved by determining the time of entry of six randomly dispersed markers, four of which are included in known groups of linked markers. The linear map of M. flagellatum reported here consists of 44 markers. PMID- 2110150 TI - Highly repetitive DNA sequences in cyanobacterial genomes. AB - We characterized three distinct families of repeated sequences in the genome of the cyanobacterium Calothrix sp. strain PCC 7601. These repeated sequences were present at a level of about 100 copies per Calothrix genome and consisted of tandemly amplified heptanucleotides. These elements were named short tandemly repeated repetitive (STRR) sequences. We used the three different Calothrix STRR sequences as probes to perform Southern hybridization experiments with DNAs extracted from various cyanobacterial strains, Bacillus subtilis, and Escherichia coli. The three different STRR sequences were found as repetitive genomic DNA components specific to the heterocystous strains tested. The role of the STRR sequences, as well as their possible use in taxonomic studies, is discussed. PMID- 2110151 TI - Control of nitrogenase recovery from oxygen inactivation by ammonia in the cyanobacterium Anabaena sp. strain CA (ATCC 33047). AB - The control of nitrogenase recovery from inactivation by oxygen was studied in Anabaena sp. strain CA (ATCC 33047). Nitrogenase activity (acetylene reduction) in cultures grown in 1% CO2 in air was inhibited by exposure to 1% CO2-99% O2 and allowed to recover in the presence of high oxygen tensions. Cultures exposed to hyperbaric levels of oxygen in the presence of 10 mM NH4NO3 were incapable of regaining nitrogenase activity, whereas control cultures returned to 65 to 80% of their original activity within about 3 h after exposure to high oxygen tension. In contrast to the regulation of heterocyst differentiation and nitrogenase synthesis, recovery from oxygen inactivation in this organism was shown to be under the control of NH4+ rather than NO3-. PMID- 2110152 TI - A transferable plasmid associated with AS-48 production in Enterococcus faecalis. AB - Enterococcus faecalis S-48 produces a peptide antibiotic, AS-48, and a bacteriocin, Bc-48. We have isolated mutants that lack these inhibitory characteristics. Further analysis of the mutants indicates that a plasmid of 56 kilobases (pMB2) may harbor the genes for AS-48. In conjugation experiments, pMB2 has been transferred into a plasmid-free OG1X strain of E. faecalis. The OG1X(pMB2) transconjugant produces the antibiotic AS-48 in solid medium, and the MIC of AS-48 for this strain is the same as that of the donor strain. PMID- 2110154 TI - Stereospecific abstraction of epsilon-pro-R-hydrogen of L-lysine by L-lysine epsilon-dehydrogenase from Agrobacterium tumefaciens. AB - The stereochemical aspects of the L-lysine epsilon-dehydrogenase reaction were examined with (6R)-L-[6-3H]lysine and (6S)-DL-[6-3H]lysine. When (6S)-DL-[6 3H]lysine was used as a substrate, the tritium was found in the product, delta 1 piperideine-6-carboxylate. In contrast, the radioactivity from (6R)-L-[6 3H]lysine was not retained in the product. Thus, the pro-R hydrogen at the prochiral C-6 carbon of L-lysine is specifically abstracted by the enzyme: the enzyme behaves stereochemically as an amino acid D-dehydrogenase. PMID- 2110153 TI - Further fractionation of the glycoprotein families of porcine zona pellucida by anion-exchange HPLC and some characterization of the separated fractions. AB - The glycoproteins of porcine zonae pellucidae have been fractionated into three families (PZP1-3) by gel filtration HPLC [Nakano et al. (1987) Biochem. Int. 14, 417-423]. However, they still comprise heterogeneous molecular species differing in electric charge. We found that sulfate, but not phosphate, is contained in PZP1-3 by a simple and rapid method for microanalysis of the anionic groups. These families were efficiently separated into many fractions by anion-exchange HPLC. When elution was performed by stepwise increase in NaCl concentration in 8 M urea/20 mM Tris-HCl, pH 8.0, a single distinctive peak emerged for each step. The analyses of amino acids, monosaccharides, and anions of the eight separated fractions of the major family, PZP3, showed that larger amounts of sulfated lactosamine linked to the constituent proteins are present in the fractions that are eluted later: the chain length and/or the chain number of these polylactosamines and the sulfate content increased with stepwise increase in NaCl concentration. Composition analyses also revealed that twice as much N glycolylneuraminic acid is present as N-acetylneuraminic acid in all fractions. The contents of these sialic acids in the fractions slightly increased in the order of elution. These results together with those of the analyses of endo-beta galactosidase digests showed that the charge heterogeneity of the porcine zona proteins is due mainly to differences in the amount of sulfated lactosamine, which is predominantly distributed in the non-reducing regions of the sugar chains. PMID- 2110155 TI - Tetrahymena actin: copolymerization with skeletal muscle actin and interactions with muscle actin-binding proteins. AB - We have previously shown that actin from Tetrahymena pyriformis has a very divergent primary structure (Hirono, M., Endoh, H., Okada, N., Numata, O., & Watanabe, Y. (1987) J. Mol. Biol. 194, 181-192) and that though it shares essential properties with skeletal muscle actin, it does not interact at all with phalloidin or DNase I (Hirono, M., Kumagai, Y., Numata, O., & Watanabe, Y. (1989) Proc. Natl. Acad. Sci. U.S. 86, 75-79). In this study, we investigated the copolymerization of this actin with skeletal muscle actin by direct observation of the heteropolymers formed from the two actins by means of electron microscopy. We also examined the binding of actin-binding proteins from skeletal muscle or smooth muscle to Tetrahymena actin by means of a cosedimentation assay. The results show that (i) Tetrahymena actin copolymerizes with skeletal muscle actin and that (ii) muscle myosin subfragment 1 binds to it in the absence of ATP, like skeletal muscle actin. However, it was also shown that (iii) muscle alpha-actinin hardly binds to Tetrahymena actin and that (iv) muscle tropomyosin does not bind to it at all. The results show that Tetrahymena actin has both properties similar and dissimilar to those of skeletal muscle actin. PMID- 2110156 TI - The 30 kDa abnormal protein in avian dystrophic muscle is indistinguishable from carbonic anhydrase III by physicochemical, immunological, and enzymological criteria. AB - In the accompanying paper, we described the existence, molecular characterization, and ontogeny of a 30 kDa abnormal protein in chicken dystrophic muscles. In this study, we have purified chicken carbonic anhydrase III and the 30 kDa protein and directly compared them. In terms of its enzymological features, the 30 kDa protein is a typical carbonic anhydrase III. Like carbonic anhydrases, it contains one mole zinc per mole of protein. The protein selectively cross-reacted with a chicken carbonic anhydrase III antibody. Antibody to the 30 kDa protein cross-reacted with chicken skeletal muscle carbonic anhydrase III. Moreover, the distribution of the abnormal protein is exactly identical to that of carbonic anhydrase III; however, there is a possibility that the 30 kDa protein is a variant of carbonic anhydrase III. Slight differences were found in antigenicities and in the apparent molecular weights of the two proteins. We have compared the two proteins by 125I-labeled two-dimensional peptide mapping. Tryptic maps have shown that the two proteins are highly homologous. Combined, these results strongly indicate that the 30 kDa protein and carbonic anhydrase III are similar, if not identical. PMID- 2110158 TI - Increase of a form of UDP-glucuronyltransferase glucuronizing various phenolic xenobiotics and the corresponding translatable mRNA in 3-methylcholanthrene treated rat liver. AB - Induction of hepatic microsomal UDP-glucuronyltransferase activity toward various phenolic xenobiotics by 3-methylcholanthrene treatment of rats was observed, and the process of the induction was studied. We had previously purified a form of UDP-glucuronyltransferase (called GT-1) having a catalytic activity toward phenolic xenobiotics from liver microsomes of 3-methylcholanthrene-treated rats. The antibodies against GT-1 inhibited the enzyme activity toward those xenobiotics in liver microsomes, and bound to a single protein having a molecular weight of about 54,000 Da (same value as that of GT-1) among microsomal proteins on immunoblotting analysis. The amount of GT-1 protein in hepatic microsomes was found to be increased in close correspondence with the activity increase by 3 methylcholanthrene treatment, by immunoblotting analysis using an uninducible cytochrome P-450 reductase as a negative standard. It was shown by in vitro translation assays that the protein increase described above resulted from the enhancement of the level of translatable mRNA encoding for GT-1. Increases in the amount of the protein immunochemically corresponding to GT-1 in the microsomes from liver of phenobarbital-treated rats and from extrahepatic organs, such as kidney, small intestine, and lung, of phenobarbital- or 3-methylcholanthrene treated rats were also observed. PMID- 2110157 TI - Modifications of substituted seryl and threonyl residues in phosphopeptides and a polysialoglycoprotein by beta-elimination and nucleophile additions. AB - The beta-elimination and nucleophile addition reactions of the substituted serine and threonine residues were studied using several synthesized fluorescence labeled phosphopeptides and a salmon egg polysialoglycoprotein (PSGP). The reagents used were 1 M CH3SH-0.43 M NaOH, 1 M NaBH4-0.1 M NaOH, 1 M CH3NH2-0.1 M NaOH, and 1 M Na2SO3-0.1 M NaOH. The beta-elimination reaction of a phosphoserine peptide, Gly-Ser(PO4)-Glu-AEAP, was about 20 times faster than that of the corresponding phosphothreonine peptide. The carboxyl-side amino acid of the phosphoamino acids in peptides greatly affected the beta-elimination rate. The beta-elimination reaction rates of O-glycosyl serine and threonine in the polysialoglycoprotein were similar and were about a half of that of the phosphoserine peptide. The rates of addition of the three nucleophiles and hydrogen to alpha-aminoacrylic acid (beta-elimination product of substituted serine) in the peptide decreased in the order of CH3SH, Na2SO3, CH3NH2, and H2(NaBH4), and the addition to alpha-aminocrotonic acid (beta-elimination product of substituted threonine) in the order of Na2SO3, CH3NH2, CH3SH, and H2. These results indicated that sulfite is the most recommended nucleophile because of its high addition rate. If sulfite addition is carried out in the presence of NaBH4, sugar chains can be released as alditols, converting the sugar-attaching amino acids to beta-sulfoamino acids. PMID- 2110159 TI - Control of the position of RNase P-mediated transfer RNA precursor processing. AB - Two Bacillus subtilis tRNA(His) precursors (Green, C. J., and Vold, B. S. (1988) J. Biol. Chem. 263, 652-657) were processed by Escherichia coli RNase P in the presence of varying [Mg2+]. The wild type precursor was processed under all conditions to afford a single tRNA product containing 8 base pairs in the acceptor stem. In contrast, the position of processing of a mutant tRNA(His) precursor (containing a G27----A27 alteration) was shown to be condition dependent. Processing occurred at A27 under conditions consistent with formation of an A27-C100 base pair in the acceptor stem but at G28 under conditions that disfavored base pair formation. The ability to control the site of RNase P mediated tRNA precursor processing is unprecedented and permits analysis of the chemical factors that promote processing. PMID- 2110160 TI - Purification and characterization of glutathione transferases with an activity toward nitroglycerin from human aorta and heart. Multiplicity of the human class Mu forms. AB - Although recent studies suggest involvement of glutathione transferase (GST) of blood vessels in vasodilation by nitroglycerin, GST forms in blood vessels remain to be studied. In this study, three GST forms (pI values 8.3, 6.6, and 4.8) were purified from human aorta and four (pI values 6.0, 5.6, 5.3, and 4.6) from the heart by affinity chromatography followed by chromatofocusing. The major form of both aorta (pI 4.8) and heart (pI 4.6) was identified as GST-pi, and the other five forms were immunologically related to GST-mu, suggesting that the five belong to the Mu class. Among nine human GST forms, including three in the Alpha class purified from the liver, GST-mu, aorta pI 8.3 form, and GST-I (a form of the Alpha class, corresponding to GST-epsilon (B1B1)) showed high activities toward nitroglycerin, 1.08, 0.85, and 0.78 units/mg protein, respectively. GST-pi did not exhibit the activity. The Km values of the aorta form (pI 8.3) for glutathione (GSH) and nitroglycerin were calculated as 0.12 and 1.1 mM, respectively. The Km values of GST-mu and GST-I for GSH were 0.29 and 0.09 mM, and those for nitroglycerin were 2.5 and 0.3 mM, respectively. The activity of the pI 8.3 form as well as GST-mu toward nitroglycerin was inhibited by bromosulfophthalein, which is known to inhibit the relaxation of rabbit aorta induced by nitroglycerin, at the lower concentration (IC50, 2 microM) than was GST-I (IC50, 32 microM). Two-dimensional gel electrophoresis and N-terminal amino acid sequence analysis revealed that five forms in the Mu class are homo- or heterodimers of five different subunits named M1 (pI 7.0/Mr 27,000), M2 (6.6/27,000), M3 (6.0/27,000), N1 (6.5/26,500), and N2 (5.9/26,500). The subunit structures of the five forms are as follows: pI 8.3 form, M1M2; 6.6 form, M2N1; 6.0 form, M3M3; 5.6 form, M3N2; and 5.3 form, N2N2. M3 and N2 seem to correspond to the subunits of GST-mu, and -4 (Board, P. G., Suzuki, T., and Shaw, D. C. (1988) Biochim. Biophys. Acta 953, 214-217), respectively. These subunits except N1 are different from each other at two or three positions in the first 20 residues of N-terminal amino acid sequence. These results indicate the presence of five different subunits in the human Mu class and also suggest that GST-M1M2 and -M2N1 found in the aorta are involved in the expression of the pharmacologic effect of nitroglycerin. PMID- 2110161 TI - Ethanolamine metabolism in cultured bovine aortic endothelial cells. AB - The role of extracellular ethanolamine in phospholipid synthesis was examined in cultured bovine aortic endothelial cells. Serine and ethanolamine were both readily accumulated by these cells and incorporated into phospholipid. Exposing cells to extracellular ethanolamine for 4-6 weeks had no effect on cell growth, yet increased the phosphatidylethanolamine content of these cells by 31% as compared to control cells. The intracellular content of ethanolamine was measured by high performance liquid chromatography, and results showed that the ethanolamine-treated cells contained a significantly greater amount of free ethanolamine compared to control cells (0.62 +/- 0.07 nmol/mg of protein versus 0.27 +/- 0.05 nmol/mg of protein, respectively). Ethanolamine-treated cells also had decreased accumulation and incorporation into lipid of [3H]ethanolamine throughout a 48-h incubation and increased K'm and V'max parameters of ethanolamine transport as compared to control cells. Studies were also done to examine the effect of ethanolamine on the generation of free ethanolamine from phosphatidylserine. In pulse-chase experiments with [3H]serine, a physiological concentration of ethanolamine (25 microM) decreased the amount of 3H-labeled phosphatidylethanolamine produced from 3H-labeled phosphatidylserine by 12 h as compared to the amount of 3H-labeled phosphatidyl-ethanolamine produced in the absence of ethanolamine in the chase incubation. Furthermore, ethanolamine treated cells accumulated 20% less labeled ethanolamine in the aqueous pool from [3H]serine after 24 h of incubation than did control cells. These results can be explained by isotope dilution with the ethanolamine pool that accumulates in these cells with time when exposed to media supplemented with a physiological concentration of ethanolamine and by an effect of ethanolamine on ethanolamine generation from phosphatidylserine. The results show that an extracellular source of ethanolamine significantly influences the phospholipid metabolism of cultured bovine aortic endothelial cells. PMID- 2110162 TI - Structure of the L5 lipopolysaccharide core oligosaccharides of Neisseria meningitidis. AB - Three different oligosaccharides were isolated by mild acid hydrolysis of the lipopolysaccharides, obtained from Neisseria meningitidis serotype 5, and their structures were elucidated by combined chemical and physical techniques. The use of 500-MHz 1H NMR in both one-dimensional and two-dimensional modes as well as nuclear Overhauser effect experiments were employed. To assist in the structural assignments the purified oligosaccharides were also degraded by chemical and enzymatic procedures to smaller fragments. The largest of the three original oligosaccharides is a triantennary partially O-acetylated decasaccharide in which the largest antenna terminates in a lacto-N-neotetraose unit. The smaller oligosaccharides (heptasaccharide and octasaccharide) except for terminal glycose deletions from the longest antenna are structural replicas of the larger. PMID- 2110163 TI - Mitochondrial phosphoenolpyruvate carboxykinase from the chicken. Comparison of the cDNA and protein sequences with the cytosolic isozyme. AB - The amino acid sequence of the mitochondrial form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-M) from the chicken was deduced from the 3571 nucleotide sequence of three overlapping cDNA clones. The derived protein sequence, which includes 607 amino acids of the mature enzyme and a leader sequence, was aligned with nine tryptic peptides of PEPCK-M and the primary sequence of the cytosolic form of PEPCK from chicken. Secondary structure predictions for the two PEPCK isozymes indicated similar packing elements of conserved, hydrophobic beta strands in the central core of the primary sequence. This core protein, which contained three GTP-binding consensus elements, was 80% identical in the two chicken isozymes, although the overall level of identity was only 63% for amino acids and 60% for nucleotides. The untranslated regions of the two cDNAs were dissimilar, although both mRNAs have potential for significant secondary structure. The PEPCK-M mRNA contained several G-C-rich regions which demonstrated free energies of formation in dyad symmetry programs up to -70 kcal/mol. The 1.6-kilobase (kb) 3'-untranslated region contained several repeat elements including one of 11 base pairs, which was present 30 times; but, a signal sequence for polyadenylation was not present. Each of the three PEPCK-M cDNA clones recognized two mRNAs of 4.2 and 3.4 kb in the livers and kidneys of starved or normally fed chickens. However, the level of these two related PEPCK-M mRNAs changed in response to cAMP treatment, with the larger mRNA predominant at 20 and 160 min and the 3.4-kb mRNA present at intermediate times. In contrast, the level of the 2.8-kb PEPCK-C mRNA increased dramatically upon addition of the cyclic nucleotide, particularly in the liver where it was not detected without cAMP induction. Thus, PEPCK-M and PEPCK-C, clearly represented the products of two distinct genes, which were distinguished by altered protein sequences and non cross-hybridizing, differentially regulated mRNAs. PMID- 2110164 TI - Expression of functional factor VIII in primary human skin fibroblasts after retrovirus-mediated gene transfer. AB - We have developed a retroviral-vector system for the transfer and expression of a cloned blood clotting factor VIII cDNA. Since inclusion of the complete cDNA into existing vectors is precluded by its large size, we deleted most codons for the B domain, which is also excised during in vivo maturation of factor VIII. When inserted into the retroviral vector M5-neoR (Laker, C., Stocking, C., Bergholtz, V., Hess, N., DeLamarter, J. F., and Ostertag, W. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 8458-8462), the sequence was shown to be efficiently expressed in murine fibroblast cell lines, as well as in primary human skin fibroblasts. Upon infection of murine fibroblast cell lines, clones containing only a single copy of the integrated vector-provirus secreted up to 125 milliunits of factor VIII antigen/10(6) cells/day. Equivalent amounts were found in a factor VIII activity assay, which signifies that the factor VIII protein secreted by the infected fibroblasts is fully functional. Primary human skin fibroblasts infected with the vector virus secreted up to 30 milliunits/10(6) cells/day. PMID- 2110165 TI - Orientation of cobra alpha-toxin on the nicotinic acetylcholine receptor. Fluorescence studies. AB - Four flourescein isothiocyanate (FITC) derivatives of Naja naja siamemsis 3 neurotoxin (alpha-toxin), labeled at the epsilon-amino groups of Lys-23, Lys-35, Lys-49, or Lys-69, and a tetramethylrhodamine isothiocyanate (TRITC) derivative, labeled at epsilon-amino group of Lys-23, were prepared and used to analyze the orientation of cobra alpha-toxin on the nicotinic acetylcholine receptor (AcChR) relative to both the plane of the membrane and the central ion channel. Fluorescence-quenching studies of the AcChR-bound FITC derivatives indicated significant solute accessibility to each site of labeling and suggested that none of the sites of FITC labeling is included in the binding surface of the alpha toxin. Labeling of Lys-23 with TRITC did not affect the affinity of the alpha toxin toward the AcChR and confirmed, contrary to some previous reports, a minimal role of Lys-23 in the binding surface of the alpha-toxin. Measurements of energy transfer between the lipid-membrane surface and the sites of labeling on receptor-bound alpha-toxin derivatives show that the relative distances of closest approach between the surface of the lipid membrane domain and the sites of labeling are in the order Lys-23 less than or equal to Lys-49 less than Lys-35 less than or equal to Lys-69. Energy transfer between AcChR tryptophans and the sites of labeling of bound derivatives was about 50% greater to Lys-49 than to Lys-23, Lys-35, or Lys-69, suggesting that Lys-49 is closer to receptor tryptophans and to the center of the extracellular domain of the receptor than Lys-23, Lys-35, or Lys-69. Combined with previous observations that the tip of the central loop of the alpha-toxin directly interacts with the AcChR, the above results suggest a model of the approximate orientation of the snake neurotoxins on the receptor. This model shows the tip of the central loop of the toxin directly interacting with the receptor surface and the major axis of the neurotoxin tilting from a perpendicular projection from the membrane. The surface of the alpha-toxin that includes Lys-23 projects away from the central ion channel and the surface that includes Lys-35 and Lys-69 faces the ion channel. PMID- 2110166 TI - Biogenesis of vacuolar membrane glycoproteins of yeast Saccharomyces cerevisiae. AB - To investigate the biogenesis of the yeast vacuole, we have sought novel marker proteins localized to the vacuolar membrane. Glycoproteins were prepared from vacuolar membrane vesicles by concanavalin A-Sepharose column chromatography and used to raise monoclonal antibodies. The antibodies obtained recognize several vacuolar proteins that have N-linked oligosaccharide chains. A set of the antibodies reacts with a vacuolar glycoprotein with a major molecular species of 72 kDa (vgp72), which appears to associate peripherally with the vacuolar membrane. The biosynthesis of vgp72 has been examined in detail by pulse-chase experiments and by analyses using various secretory mutants (sec18, sec7, and sec1) and a vacuolar protease mutant (pep4). vgp72 first appears in the endoplasmic reticulum as a 74-kDa species and is quickly modified in the Golgi apparatus to two distinct species: a 79-kDa form, and a heterogeneously glycosylated form (90-150 kDa). Subsequently, both species are proteolytically processed in the vacuole giving rise to a 72-kDa species as well as heavily glycosylated form. Thus, the biogenesis of vgp72 utilizes the early part of the secretory pathway as is the case of vacuolar soluble enzymes. A unique feature is that two species that are different in the extent of glycosylation appear to follow the same destination to the vacuolar membrane. PMID- 2110167 TI - Evidence for difference in the roles of two cysteine residues involved in disulfide bond formation in the folding of human lysozyme. AB - Human lysozyme is made up of 130 amino acid residues and has four disulfide bonds at Cys6-Cys128, Cys30-Cys116, Cys65-Cys81, and Cys77-Cys95. Our previous results using the Saccharomyces cerevisiae secretion system indicate that the individual disulfide bonds of human lysozyme have different functions in the correct in vivo folding and enzymatic activity of the protein (Taniyama, Y., Yamamoto, Y., Nakao, M., Kikuchi, M., and Ikehara, M. (1988) Biochem. Biophys. Res. Commun. 152, 962 967). In this paper, we report the results of experiments that were focused on the roles of Cys65 and Cys81 in the folding of human lysozyme protein in yeast. A mutant protein (C81A), in which Cys81 was replaced with Ala, had almost the same enzymatic activity and conformation as those of the native enzyme. On the other hand, another mutant (C65A), in which Cys65 was replaced with Ala, was not found to fold correctly. These results indicate that Cys81 is not a requisite for both correct folding and activity, whereas Cys65 is indispensable. The mutant protein C81A is seen to contain a new, non-native disulfide bond at Cys65-Cys77. The possible occurrence of disulfide bond interchange during our mapping experiments cannot be ruled out by the experimental techniques presently available, but characterization of other mutant proteins and computer analysis suggest that the intramolecular exchange of disulfide bonds is present in the folding pathway of human lysozyme in vivo. PMID- 2110168 TI - The sustained second phase of hormone-stimulated diacylglycerol accumulation does not activate protein kinase C in GH3 cells. AB - Numerous hormones activate cells through receptor-regulated hydrolysis of phosphoinositides resulting in elevated cellular diacylglycerol (DAG), an activator of protein kinase C (PKC). Our previous studies showed that thyrotropin releasing hormone (TRH) treatment of GH3 cells stimulated a rapid (less than 10 s) but transient (less than 60 s) association of cytosolic PKC with the membrane. In this study, we investigated the roles of hormone-stimulated Ca2+ and DAG levels in initiating and terminating the membrane association of PKC. The initial effects of TRH were not mimicked by elevating CA2+ levels, however, inhibiting TRH-stimulated Ca2+ increases blocked hormone-stimulated PKC translocation. Hence, the TRH stimulation of both Ca2+ and DAG levels were essential for the initial PKC translocation. The termination of PKC membrane association could not be attributed to proteolysis of PKC nor to limiting Ca2+ levels. Treatment of cells with phorbol diesters potentiated and prolonged the effects of TRH on PKC translocation, suggesting that DAG levels limited the membrane association of PKC. Since TRH stimulated a sustained increase in DAG levels, DAG composition was analyzed. There was a marked shift in DAG from tetraenoic (at 15 s) to more saturated DAGs at longer times. In addition, increases in plasma membrane DAG in response to TRH were transient rather than sustained. We propose that the TRH stimulation of PKC translocation is short-lived due to the metabolism of plasma membrane DAGs which are effective in promoting PKC activation. In contrast, DAGs which accumulate in intracellular membranes during the sustained phase of TRH treatment appear to be ineffective as activators of PKC. PMID- 2110170 TI - Secondary peritonitis and intra-abdominal abscess. PMID- 2110169 TI - Tissue plasminogen activator messenger RNA levels increase in cultured human endothelial cells exposed to laminar shear stress. AB - Fluid shear stress can stimulate secretion of tissue plasminogen activator (tPA) by cultured human endothelial cells, while plasminogen activator inhibitor type-1 secretion remains unstimulated. To determine whether hemodynamically induced changes in tPA messenger RNA (mRNA) levels also occur, primary cultures from the same harvest of primary human umbilical vein endothelial cells were either maintained in stationary culture or exposed to arterial levels of shear stress (25 dynes/cm2) for 24 hours. Total cellular RNA was isolated from the shear stressed and stationary cultures and the relative levels of tPA mRNA and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA were determined using a coupled reverse transcriptase/polymerase chain reaction method. As indicated by the amount of amplification product, tPA mRNA levels were many fold higher (greater than 10) in endothelial cells subjected to shear stress for 24 hours than in stationary controls. In contrast, mRNA levels for GAPDH were similar in control and shear stressed cells. The constancy of the measured GAPDH signal indicated that the tPA response was a selective effect of fluid shear stress. When a similar polymerase chain reaction method was used, the mRNA levels of basic fibroblast growth factor (bFGF) were found not to vary in comparison to GAPDH mRNA after 24 hours of shear stress. These results indicate that enhancement of the fibrinolytic potential of endothelial cells in response to hemodynamic forces could involve transcriptional events. PMID- 2110171 TI - Was HELLP at hand? PMID- 2110173 TI - Ventricular tachycardia or aberrancy? PMID- 2110172 TI - The probability of a probability. PMID- 2110175 TI - Scraping the bottom. PMID- 2110174 TI - Hepatic fibrosis: new insights into pathogenesis. AB - From available clinical and experimental data, the deterioration of hepatocellular function associated with fibrosis may be ascribed, in part, to loss of biologic support provided by a normal extracellular matrix. These studies of pathogenesis are expected to clarify new points of therapeutic intervention and also to rationalize empiric therapies. PMID- 2110176 TI - Antibacterial therapy: problems and promises, Part I. AB - Agents approved for clinical use in the past five years and others most likely to be available in the near future are evaluated in this two-part review. This installment is devoted entirely to the beta-lactam antibiotics--penicillins, cephalosporins, monobactams, and carbapenems. There are more similarities than differences among them, but the variations give each agent a range of appropriate uses. PMID- 2110177 TI - Viral persistence and immune dysfunction. AB - Viruses can persist for years without provoking an effective host immune response or otherwise causing the cell destruction characteristic of an acute viral infection. Clinically relevant principles, generalizable to many persistent viruses, are exemplified by measles and lymphocyte choriomeningitis viruses. The LCMV model indicates that viral persistence and the anergic state are reversible. PMID- 2110178 TI - Health care: defining the high ground. PMID- 2110179 TI - Serological classification by monoclonal antibodies of Rickettsia tsutsugamushi isolated in Korea. AB - Antigenic types of 113 strains of Rickettsia tsutsugamushi isolated from Korean patients were analyzed by using murine polyclonal and monoclonal antibodies. The isolates can be classified in six groups according to their reaction to a panel of monoclonal antibodies. Nine isolates of group I were identified as the Gilliam serotype, and 13 isolates of groups II and III were identified as the Karp serotype. There were two groups that were considered to be a mixture of groups I and II or groups I and III, respectively. The remaining 88 strains of group IV had a unique antigenic determinant that was not present in the prototype strains (Karp, Kato, Gilliam), in addition to sharing common antigens with the prototype strains. Therefore these strains, which are more prevalent in Korea, seem to belong to a new serotype closely related to the Karp serotype. PMID- 2110180 TI - Enzyme immunoassay for identification of heat-killed mycobacteria belonging to the Mycobacterium tuberculosis and Mycobacterium avium complexes and derived from early cultures. AB - A simple enzyme-linked immunosorbent assay was developed for the identification of cultured mycobacteria belonging to the Mycobacterium tuberculosis complex, the Mycobacterium avium complex, and Mycobacterium kansasii. Six monoclonal antibodies were used: two (F23-49 and F24-2) were specific for the M. tuberculosis complex, two (F85-2 and F85-10) were specific for the identification of the M. avium complex, one (F126-22) was specific for M. kansasii, and one (F141-3) was broadly reactive and distinguished mycobacteria from other bacteria. In the enzyme-linked immunosorbent assay only 10(6) to 10(7) bacteria derived from early cultures (2 to 3 weeks) were needed for each monoclonal antibody. For the M. tuberculosis complex the sensitivity and specificity were both 100%. For the M. avium complex the specificity was 100% and the sensitivity was 70%. The three M. kansasii strains tested could all be identified as M. kansasii. PMID- 2110182 TI - Ampicillin-resistant enterococci. PMID- 2110181 TI - Immunoglobulin A and immunoglobulin G antibody responses to alginates from Pseudomonas aeruginosa in patients with cystic fibrosis. AB - Patients with cystic fibrosis have a high prevalence of mucoid, alginate producing Pseudomonas aeruginosa that causes chronic infection of the mucosal surface of the lungs. We developed enzyme-linked immunosorbent assays (ELISAs) for determination in serum of immunoglobulin A (IgA) and IgG antibodies to alginate purified from P. aeruginosa and an ELISA for detection of IgA antibodies to a polyvalent P. aeruginosa standard antigen. Absorption experiments indicated that the assays were antigen and antibody specific and had analytical variations that ranged from 7 to 19%. Serum samples from 207 patients with cystic fibrosis, 100 healthy children, and 94 healthy adults were examined. The patients responded to P. aeruginosa infection with early IgA and IgG antibody responses that were significantly higher than in controls and noncolonized patients. Analysis of paired serum samples showed that infected patients had an increase in specific IgG and IgA antibodies that was significantly higher than in noncolonized patients. The serological data were analyzed for correlation with clinical condition; poor lung function was significantly associated with increased levels of IgA and IgG antibodies to P. aeruginosa alginate and to the standard antigen and with a relative excess of IgA antibodies to the standard antigen compared with IgA antibodies to P. aeruginosa alginate. The assays showed high predictive values if positive, but a negative test did not exclude infection, and the ELISAs should not be used for diagnostic purposes. Mucoid strains were present initially in the sputa of 28 of 54 infected patients with paired serum samples. These patients had a significant increase in anti-alginate antibodies, but it was not different from the increase seen in patients infected only with nonmucoid strains. Therefore, alginate may also be produced in vivo by nonmucoid P. aeruginosa. The study showed that early formation of IgA and IgG antibodies to P. aeruginosa alginate did not prevent development of chronic infection and that P. aeruginosa-specific IgA antibodies correlate with poor lung function. PMID- 2110183 TI - Lymphocyte infiltration into normal rat brain following hyperosmotic blood-brain barrier opening. AB - An investigation was conducted to determine whether lymphocytes were able to infiltrate into the brain parenchyma of normal rats in which hyperosmotic opening of the blood-brain barrier (BBB) had been created by internal carotid infusion of filtered 20% mannitol. Various numbers (1 x 10(6) to 3 x 10(8] of autologous lymphocytes were injected into the internal carotid artery, or via a tail vein, after BBB opening. Lymphocytes were detectable in the brain of rats subjected to high-grade BBB opening and injected with a high number of lymphocytes. Subsets of lymphocytes were examined by immunohistochemical staining using OX19, W3/25 and OX8 monoclonal antibodies. There was no remarkable difference in number between W3/25- and OX8-positive cells. From these results it was suggested that the intensity of BBB opening and the number of lymphocytes flowing in brain vessels are related to the passage of lymphocytes through the BBB. PMID- 2110184 TI - Arginine vasopressin-binding peptides derived from the bovine and rat genomes differ in their abilities to block arginine vasopressin modulation of murine immune function. AB - Previously we reported on a nonapeptide (binding peptide) derived by reading the complementary DNA strand of the bovine arginine vasopressin (AVP) gene in the 3'5' direction that specifically blocks the AVP helper signal for gamma interferon (IFN gamma) production by helper cell-depleted mouse spleen cultures. Bovine 5'3' AVP-binding peptide, however, did not block AVP activity. We report here on the relative abilities of 5'3' and 3'5' AVP-binding peptides derived from the bovine and rat AVP genes to block the AVP helper signal for IFN gamma production. The sequences of the bovine and rat 5'3' AVP-binding peptides differ by two amino acids, whereas the 3'5' AVP-binding peptides derived from both genes are the same. In contrast to the lack of blocking activity of the bovine 5'3' AVP binding peptide, the rat 5'3' AVP-binding peptide was almost as effective as the 3'5' AVP-binding peptide in blocking AVP function. No effect was seen with a 9 amino acid control peptide consisting of a 'scrambled' 3'5' AVP-binding peptide sequence. Further, polyclonal anti-rat 5'3' AVP-binding peptide antibodies blocked AVP activity, whereas polyclonal anti-bovine 5'3' AVP-binding peptide antibodies had no significant effect. Polyclonal antibodies generated against the 3'5' AVP-binding peptide also blocked AVP activity. These antibodies possibly blocked AVP function by interaction with the lymphocyte AVP receptor, since AVP specifically displaced binding of the antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110185 TI - The inhibitory effect of tumor necrosis factor and interleukin-1 on Ia induction by interferon-gamma on endothelial cells from murine central nervous system microvessels. AB - The effect of both tumor necrosis factor-alpha (TNF) and interleukin-1 (IL-1) on interferon-gamma (IFN)-induced Ia expression was studied using cultured endothelial cells (EC) isolated from cerebral microvessels of SJL mice. TNF inhibited Ia induction by IFN in a dose-dependent manner. The degree of inhibition by TNF was related to the IFN concentration: 200 U/ml TNF inhibited Ia expression induced by 20 U/ml IFN by 80% and Ia induced by 100 U/ml IFN by 45%. FACS analysis revealed the induction of Ia antigen on 30-40% of EC after 3 days' culture with IFN; TNF significantly reduced the percent of EC expressing Ia antigens. Identical treatment of SJL astrocytes showed TNF augmented Ia expression induced by IFN. IL-1 also inhibited Ia induction by IFN in a manner similar to that observed with TNF. The percent reduction of Ia-positive EC by Il 1 (2.0 U/ml) was 30% and 50% during incubations with 100 and 20 U/ml IFN, respectively. When combined at suboptimal concentrations IL-1 and TNF synergistically inhibited Ia expression induced by IFN. These results demonstrate that TNF acts on EC and astrocytes in a disparate manner and indicate that TNF and IL-1 can synergistically down-regulate immune responses involving central nervous system EC. PMID- 2110186 TI - Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus. AB - A murine cell line (BV-2) has been generated by infecting primary microglial cell cultures with a v-raf/v-myc oncogene carrying retrovirus (J2). BV-2 cells expressed nonspecific esterase activity, phagocytic ability and lacked peroxidase activity. Such cells secreted lysozyme and, following appropriate stimulation, also interleukin 1 and tumor necrosis factor. Furthermore, BV-2 cells exhibited spontaneous anti-Candida activity and acquired tumoricidal activity upon treatment with interferon-gamma. Phenotypically, BV-2 cells resulted positive for MAC1 and MAC2 antigens, and negative for MAC3, glial fibrillary acidic protein (GFAP) and galactocerebroside (GC) antigens. Since BV-2 cells retain most of the morphological, phenotypical and functional properties described for freshly isolated microglial cells, we can conclude that J2 virus infection has resulted in the immortalization of active microglial cells. PMID- 2110187 TI - Increased numbers of T lymphocytes with gamma delta-positive antigen receptors in a subgroup of individuals with pulmonary sarcoidosis. AB - Individuals with sarcoidosis were evaluated for preferential usage of T cells with the gamma delta-positive (+) type of T cell antigen receptor. Compared with normal subjects (n = 19), the group with sarcoidosis had increased numbers of CD3+ alpha beta-negative (-) T cells in the blood (normal, 58 +/- 12 cells/microliters; sarcoid, 192 +/- 45 cells/microliters, P less than 0.05) and in the epithelial lining fluid of the lung (normal, 78 14 cells/microliters; sarcoid, 240 +/- 60 cells/microliters, P less than 0.04) and a concomitant elevated number of blood and lung CD3+ gamma delta+ T cells, owing to a striking increase in the number of CD3+ gamma delta+ T cells in a subgroup (7 of 20) of sarcoid individuals. The elevated numbers of sarcoid blood gamma delta+ T lymphocytes were mostly Ti gamma A+ and delta TCS1-, a pattern also seen in normal individuals, consistent with the majority of gamma delta+ T cells expressing one gamma-chain variable region, V gamma 9. The observation of an increase in the total gamma delta+ T cell numbers in a sarcoid subgroup suggests that various specific stimuli may trigger the expansion of different T cell subpopulations within different groups of individuals with sarcoidosis. PMID- 2110188 TI - Molecular characterization of a somatically mutated anti-DNA antibody bearing two systemic lupus erythematosus-related idiotypes. AB - We report the molecular characterization of 2A4, an IgG, DNA-binding antibody bearing the 3I and F4 idiotypes which are associated with anti-DNA antibodies in serum of patients with systemic lupus erythematosus (SLE). The antibody is produced by an EBV-transformed B cell line derived from a patient with multiple myeloma whose myeloma protein is also an IgG, 3I-reactive, F4-reactive, DNA binding immunoglobulin, although the 2A4 antibody does not itself represent the myeloma protein. The 2A4 heavy chain is encoded by a VH4 gene, a D-D gene fusion and the JH6 gene; the light chain is derived from a Vk1 gene and the Jk2 gene. This is the first human antibody shown to have a CDR3 encoded by a D-D fusion. DNA sequence analysis of the 2A4 VH gene together with a Southern blot of genomic DNA probed with a 2A4 VH-specific oligonucleotide strongly suggest it to be somatically mutated. The data provide evidence that human autoantibodies can be products of somatically mutated genes and suggest that the 2A4 antibody may reflect the selective pressure of antigen. PMID- 2110189 TI - Preventive effect of long-term aldose reductase inhibition (ponalrestat) on nerve conduction and sural nerve structure in the spontaneously diabetic Bio-Breeding rat. AB - To test the hypothesis that aldose reductase inhibition may prevent or delay the development of functional and structural neuropathy in the insulin-deficient diabetic Bio-Breeding rat (BB-rat), hyperglycemic rats were begun on the aldose reductase inhibitor (ARI) ponalrestat 25 mg/kg body wt soon after the onset of diabetes and followed for 4 or 6 mo. Ponalrestat treatment completely prevented the characteristic nerve conduction slowing and structural abnormalities of the node of Ranvier for 4 mo despite only partial preservation of axonal integrity. Ponalrestat treatment for 6 mo achieved a partial but significant prevention of nerve conduction slowing, axoglial dysjunction, and axonal degenerative changes. This incomplete but significant prevention of neuropathy by ponalrestat suggests that additional mechanisms besides polyol-pathway activation may be of importance in the pathogenesis of diabetic neuropathy. Alternatively, the dosage used in the present study may not have been sufficient to achieve a complete prevention. Despite the only partial protective effect of ARI treatment on degenerative peripheral nerve changes in hyperglycemic BB-rats, 6 mo of treatment resulted in a more than threefold increase in regenerating nerve fibers. These data suggest that prophylactic ARI treatment may be efficacious in delaying the development of diabetic neuropathy. PMID- 2110191 TI - Clinical modeling of T cell vaccination against autoimmune diseases in rats. Selection of antigen-specific T cells using a mitogen. AB - Effective T cell vaccination against experimental autoimmune diseases involves treatment with activated, autoimmune T lymphocytes. The present study was undertaken to learn whether antigen-specific T cells present in low frequency could be selected in vitro without using the specific antigen. The rat models of adjuvant arthritis and experimental autoimmune encephalomyelitis were investigated using proliferation assays and limiting dilution techniques to quantify the changes in reactivity of a heterogenous population of lymphocytes to the relevant antigen. Stimulation with concanavalin A for 2 d and then culture in IL-2-containing medium led to a substantial increase in the activity and frequency of the specific autoimmune T cells. Enrichment of antigen-specific T cells could be demonstrated using lymph node, spleen, or peripheral blood lymphocytes, from rats late in the course of disease. The effect was not evident in lymphocytes from the thymus. These results are relevant to the clinical application of T cell vaccination and to investigation of self-antigens in autoimmune disease. PMID- 2110190 TI - Constitutive and inducible expression of HLA class II determinants by human osteoblast-like cells in vitro. AB - Activated immune cells release cytokines which modulate the activity of bone cells in vitro. Expression of major histocompatibility complex (HLA in humans) class II determinants on bone surface cells may be important in local immune cell activation. In this study, expression of HLA-DR and DQ by cultured human bone cells (HBC) derived from normal trabecular bone surfaces was assessed by fluorescence-activated cell sorter (FACS) analysis and immunoperoxidase techniques using monoclonal antibodies. A subset of HBC (10-30%) expressed DR constitutively while 5-15% displayed DQ during long-term culture. HBC lacked a number of monocyte and lymphocyte markers. In addition, both DR+ and DR- HBC (FACS separated) produced osteocalcin stimulated by 1,25-dihydroxyvitamin D2 (1,25(OH)2D3). This suggests that both phenotypes belong to the osteoblast lineage. The number of DR+ HBC was increased by interferon-gamma (IFN gamma; 40 95% DR+ cells) whereas DQ+ HBC remained unchanged or was slightly increased (5 20% DQ+ cells). Moreover, 1,25(OH)2D3 enhanced IFN gamma-induced DR expression and at high concentration (10(-7) M) augmented DR expression by itself. Other major osteotropic factors, parathyroid hormone, interleukin 1, and calcitonin, did not affect HBC DR expression. The findings suggest that HBC may participate in activation of the immune system and that some osteotropic factors may regulate this function. PMID- 2110192 TI - Regulation of immunoglobulin (Ig)E synthesis in the hyper-IgE syndrome. AB - The hyper-IgE (HIE) syndrome is characterized by high IgE serum levels, chronic dermatitis, and recurrent infections. The mechanisms responsible for hyperproduction of IgE in HIE patients are presently unknown. We investigated whether spontaneous in vitro IgE synthesis by PBMC from seven HIE patients was sensitive to signals (cell adhesion, T/B cell cognate interaction and lymphokines: IL-4, IL-6, and IFN-gamma) known to regulate IgE induction in normals. Our results show that, unlike IL-4 dependent IgE synthesis induced in normals, spontaneous IgE production by PBMC from HIE patients was not blocked by monoclonal antibodies to CD2, CD4, CD3, and MHC class II antigens. Furthermore, antibodies to IL-4 and IL-6 did not significantly suppress IgE production. IFN gamma had no significant effects on spontaneous in vitro IgE synthesis. To test whether an imbalance in lymphokine production might underlie hyperproduction of IgE in HIE patients, mitogen-induced secretion of IL-4 and IFN-gamma by PBMC was assessed. No significant difference was detected between HIE patients and normal controls. Thus, ongoing IgE synthesis in the HIE syndrome is largely independent of cell-cell interactions and endogenous lymphokines, and is due to a terminally differentiated B cell population, no longer sensitive to regulatory signals. PMID- 2110193 TI - Characterization of antibody labelled colloidal gold particles and their applicability in a sol particle immuno assay (SPIA). AB - This study describes the characterization of antibody labelled colloidal gold particles and their applicability in a sol particle immuno assay (SPIA) to quantify murine monoclonal antibodies of all IgG isotypes. Two physical methods (transmission electron microscopy (TEM) and dynamic light scattering (DLS], were used to obtain information about particle size and morphology of the gold sols, but only with DLS antibody labelling could be detected. In addition, electrophoretic methods like agarose electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed also that antibody labelling was successful. The biological activity of the antibody gold conjugates was determined by using them in a SPIA and as an electrondense marker in an immunogold labelling procedure to visualize meningococcal surface exposed outer membrane proteins labelled with monoclonal antibodies. The SPIA was applicable to determine murine monoclonal antibodies of all IgG isotypes with a sensitivity of 20-80 ng/ml and a coefficient of variation of 6.7 +/- 2.2%. PMID- 2110194 TI - A heterogeneous double antibody enzyme-linked immunoassay to measure beta galactosidase fusion protein. AB - A rapid and sensitive enzyme-linked immunoassay (ELISA) to quantitate recombinant fusion proteins encoded by cloned cDNA in the bacteriophage lambda gt11 is described. Since the fusion protein is expressed in an equimolar ratio to beta galactosidase, the assay derives the concentration of the recombinant protein in total bacterial lysates or pure preparations from the measurement of beta galactosidase with an enzyme-linked immunoassay. This assay is a useful technique to measure the recombinant proteins for subsequent immunological and biochemical characterization. PMID- 2110195 TI - Lupus cofactor phenomenon. PMID- 2110196 TI - Thyrotropin-releasing hormone-immunoreactive nerve terminals synapse on the dendrites of gastric vagal motoneurons in the rat. AB - Thyrotropin-releasing hormone stimulates vagally mediated gastric acid secretion and motility by an undefined central mechanism in the rat. The present study sought to determine the anatomical basis for this stimulatory effect by examining the ultrastructural relationship of nerve terminals immunoreactive for thyrotropin-releasing hormone with the dendrites of gastric vagal motoneurons. A light and electron microscopic double immunostaining technique was employed using the beta subunit of unconjugated cholera toxin as a neural tracer. Cholera toxin (50 microliters, 0.25%) was injected into the ventral stomach musculature in five rats. After 72 hours' survival, animals were sacrificed by transcardiac perfusion fixation. Retrogradely transported cholera toxin was immunocytochemically localized in vagal gastric motoneurons and their dendrites in the dorsal motor nucleus of the vagus and nucleus of the solitary tract, alone or in combination with the immunocytochemical localization of thyrotropin-releasing hormone. Ultrastructural analysis of double-labeled material revealed thyrotropin releasing hormone-immunoreactive nerve terminals making asymmetric synaptic contacts on the retrogradely labeled dendrites of vagal gastric motoneurons. Nerve terminals immunoreactive for thyrotropin-releasing hormone also made asymmetric and symmetric synaptic contacts with unlabeled dendrites of undetermined perikaryal origin. In addition, nonsynaptic varicosities immunoreactive for thyrotropin-releasing hormone were frequently observed in the vagal nuclei. The synaptic contacts between thyrotropin-releasing hormone immunoreactive nerve terminals and vagal gastric motoneuronal dendrites provide one possible basis for the profound stimulatory effect of central thyrotropin releasing hormone on gastric vagal motor activity. PMID- 2110197 TI - Interactions between histamine and prostanoids in IgE-dependent, late cutaneous reactions in man. AB - The contribution of histamine and cyclooxygenase metabolites of arachidonic acid to the wheal-and-flare reaction (WFR) (0 to 30 minutes) and the late cutaneous reaction (LCR) (1 to 24 hours) evoked by intradermal injection of antihuman IgE was appreciated in a comprehensive study of human volunteers treated with H1 and H2 antihistamines, cyclooxygenase inhibitors, as well as the combination of both types of drugs. The findings reinforce the concept that histamine is the major, but not exclusive, mediator of the WFR. In contrast, histamine accounted for but a limited portion of the LCR, but 48 hours of pretreatment with three different cyclooxygenase inhibitors, acetylsalicylic acid, indomethacin, or diclofenac sodium, had but a minor influence on the WFR, whereas all drugs produced a distinct overall inhibition of the LCR. However, for indomethacin, the inhibition was preceded by a potentiation (at 1 to 2 hours), which was abolished by antihistamines, suggesting increased histamine release from skin mast cells after cyclooxygenase inhibition. Furthermore, there was synergism between indomethacin and antihistamines during the LCR, and the combination of diclofenac sodium with antihistamines produced additive inhibition. It is proposed that cyclooxygenase products, such as prostaglandins and thromboxanes, contribute to IgE-dependent skin reactions, both as modulators of mediator release and as vasoactive mediators. PMID- 2110198 TI - Cromolyn sodium in the management of systemic mastocytosis. AB - A multicenter, double-blind, placebo-controlled trial of the efficacy of oral cromolyn sodium (200 mg orally four times per day) was conducted in 11 patients with systemic mastocytosis who had been maintained with the drug on an individualized compassionate-need basis. Efficacy was measured by physician assessment of overall disease severity based on history and physical examination at specified intervals and by the average daily patient symptom diary scores for each of three mastocytosis-related symptoms that had previously appeared to be alleviated by the use of this drug. Efficacy variables were compared for a 4-week baseline period, during which patients received open-labeled cromolyn sodium, and at 4-week intervals during a 16-week period of random assignment to cromolyn sodium or placebo. Overall disease severity and symptoms recorded in patient diaries were graded on a scale of 0 (absent) to 5 (incapacitating). The average physician assessment of disease severity and symptom scores of the patients in the placebo-treated group increased significantly during the randomization phase relative to patients in the cromolyn sodium-treated group, reflecting an exacerbation of symptoms with drug withdrawal (p less than 0.05 and less than 0.028, respectively). When the symptom scores were analyzed separately for gastrointestinal manifestations of disease (diarrhea, abdominal pain, nausea, and vomiting), cromolyn sodium treatment was significantly beneficial relative to placebo (p less than 0.02), whereas the benefit for nongastrointestinal manifestations did not reach statistical significance. PMID- 2110199 TI - Lack of suppression of IgE production by recombinant interferon gamma: a controlled trial in patients with allergic rhinitis. AB - Recent evidence suggests that interferon-gamma (IFN-gamma) is a potent inhibitor of IgE synthesis in rodents. We conducted a randomized, placebo-controlled, two period clinical trial of human recombinant IFN-gamma in the treatment of allergic rhinitis. Forty-five adults with well-documented ragweed-allergic rhinitis were randomized into three groups of 15 adults each and received subcutaneous injections three times weekly. The first treatment period (4 weeks during the off season) began on April 18, 1988; the second treatment period (6 weeks during ragweed pollination) began on August 15, 1988. All subjects received the same treatment in both periods. Group 1 received 0.2 mg per injection of IFN, group 2 received 0.02 mg of IFN, and group 3 received placebo. One subject in group 1 and three subjects in group 2 withdrew because of adverse reactions, and three subjects withdrew for personal reasons. There were no significant differences in mean weekly symptom scores or supplemental medication scores among the three groups in either treatment period. Furthermore, there were no significant differences in the changes of serum IgE antibody to crude ragweed extract or in serum total IgE among the three groups during or before the ragweed-pollination season. These results indicate that this treatment regimen with IFN-gamma does not alter IgE production in patients with ragweed hay fever and indicate the need for further clinical research of lymphokine modulation of IgE production. PMID- 2110200 TI - Abridged brief as amicus curiae of the American Geriatrics Society. PMID- 2110201 TI - Abridged brief as amicus curiae of the Society for the Right to Die, Inc. PMID- 2110202 TI - Abridged brief as amici curiae of the Association for Retarded Citizens of the United States. PMID- 2110204 TI - Surrogate decisions at risk. The Cruzan case. PMID- 2110203 TI - The case of Ms. Nancy Cruzan and the care of the elderly. AB - The case of Ms. Nancy Cruzan is the first so-called "right to die" case to be heard by the US Supreme Court. The Missouri Supreme Court had ruled that Ms. Cruzan's parents, who are also her court-appointed guardians, cannot authorize the withdrawal of artificial hydration and nutrition from their daughter. Ms. Cruzan has been in a persistent vegetative state since an auto accident more than six years ago. Even though Ms. Cruzan is only 32 years old, the decision in her case will have serious implications for care of the elderly. Key features of the Missouri Supreme Court decision include their claims that (1) the authority for surrogate decision-making flows from the parens patriae power of the State rather than from the authority of the incompetent person, (2) the State has an unqualified interest in the preservation of life, and (3) the medical provision of nutrition and hydration ought to be considered differently than other forms of medical treatment. Such claims are at considerable variance from accepted standards of ethically defensible decision-making that focus on the well-being of the patient understood according to the patient's own values and life goals. If the US Supreme Court restricts decisions to forgo life-sustaining treatment according to patient prognosis, capacity for decision-making, type of treatment, or state of residence, then a patient-centered standard of medical decision making will be impossible to sustain and the maximization of life extension will be required without regard to the suffering thereby imposed. PMID- 2110205 TI - Detection of HIV antibody and antigen (p24) in residual blood on needles and glass. AB - There is a significant rate of percutaneous injury with needles during the care of patients with acquired immunodeficiency syndrome (AIDS). Following puncture injury, it is recommended that the source of the contaminating blood be checked, and if human immunodeficiency virus-type 1- (HIV-1)-seropositive, zidovudine prophylaxis be considered. As the source of contaminating blood may be unknown, we studied the detectability of HIV-1 antibody and circulating antigen (p24) in the residual blood from needles and pieces of glass at various intervals following exposure to blood. The residual volume of blood remaining in needles varied from 183 +/- 50 microliters for a 20 G needle to 7.8 +/- 1 microliter for a 27 G needle, and the residual blood on small pieces of glass varied from 23 microliters for a piece weighing 558 mg to 2 microliters for a piece weighing 21 mg. Analysis of washed samples of residual blood from all 20 G through 26 G needles and from broken pieces of glass larger than 0.41 g that had been exposed to HIV-1-seropositive blood and left at room temperature for one hour, one day and one week resulted in positive tests for HIV-1 antibody by enzyme-linked immunosorbent assay (ELISA), immunofluorescence and Western blot assays. The circulating antigen was detected in residual blood of 20 G through 26 G needles, but not from contaminated pieces of glass. This technique could be applied to situations where a healthcare worker pricked him- or herself with a needle or with a piece of glass that had been contaminated with blood of unknown seroreactivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110206 TI - A controlled study of fluvoxamine and exposure in obsessive-compulsive disorder. AB - DSM-3 obsessive-compulsive out-patients were randomly assigned to fluvoxamine with antiexposure (F), fluvoxamine with exposure (Fe), or placebo with exposure (Pe) for 24 weeks. Of 65 patients offered treatment 60 entered the trial, 50 reached week 8, 44 completed treatment to week 24, and 37 reached follow up to week 48. On average the patient had depressed mood (mean Hamilton depression rating scale = 19). Drop-out numbers, clinical status and behavioural measures were comparable across groups. Most F patients did not do antiexposure, but Fe and Pe patients complied in doing exposure. All three groups improved in rituals and depression from week 0 to week 24 and 48, with a slight but non-significant superiority for combined treatment up to week 24. At week 8 there was a drug between-group effect on rituals, but not on depression. At week 24 there was a drug between-group effect on depression, but not on rituals. The drug superiority was short-lived. At week 48 there was no between-group difference in rituals or depression. Depression was related to ritual outcome at week 24 in F, and tended to be so in Fe. PMID- 2110207 TI - Mitomycin C-induced sister chromatid exchange in X chromosomes of Bovidae. AB - Sister chromatid exchanges (SCEs) in early- and late-replicating X chromosomes of seven female cattle (Bos taurus L.) and five female river buffalo (Bubalus bubalis L.) were studied in untreated lymphocytes and lymphocytes treated with mitomycin C (MMC). In the experiment, 577 SCEs on X chromosomes of MMC-untreated cells and 825 SCEs on X chromosomes of MMC-treated cells from both species were observed. No significant differences between the number of SCEs in early- and late-replicating X chromosomes were found even when singular species and subjects were considered. PMID- 2110208 TI - Production and characterization of a monospecific antiserum (A128) to disaggregated Alzheimer paired helical filaments. AB - Paired helical filaments (PHF), which constitute neurofibrillary tangles (NFT) and neuritic plaque (NP) neurites, serve as a useful marker for Alzheimer disease (AD). We have isolated AD PHF in a highly purified and disaggregated form for use as an immunogen to produce a heterologous polyclonal antiserum in rabbits. One rabbit was maintained long-term for the high quality of the antiserum it produced. Through absorptions with normal brain tissue, we were able to produce a monospecific antiserum which reacts only with NFT and NP neurites in AD brain tissue sections. We further demonstrated the specificity of this antiserum by electron microscopic immunohistochemistry, gel diffusion analysis, and immunoblotting. This antiserum also showed immunoreactivity to NFT of Down syndrome and progressive supranuclear palsy, and to the Pick bodies of Pick disease, but not to the Lewy bodies of idiopathic Parkinson disease. This well characterized antiserum, all from one rabbit, offers several unique advantages to the study of the nature, origin, and interrelationships of filamentous protein abnormalities in AD and other neurodegenerative disorders. PMID- 2110209 TI - Double-labeling of tissue containing the carbocyanine dye DiI for immunocytochemistry. AB - The fluorescent carbocyanine dye DiI can be used for retrograde and anterograde labeling of neuronal pathways. To investigate the possible neurochemical identity of DiI-labeled neuronal cell bodies and terminals, we used a procedure for double labeling of the same tissue with antisera to specific neuroactive substances. This procedure involves visualizing the immunohistochemical label with an FITC conjugated secondary antiserum. Both labels can be viewed in the same tissue by fluorescence microscopy, and individual cell bodies and processes double-labeled with DiI and antiserum can be identified by switching between filter sets appropriate for rhodamine (to see the DiI labeling) and for fluorescein (to see the immunhistochemical labeling). The method has been used with primary antisera to excitatory and inhibitory amino acid neurotransmitters, as well as to neuropeptides, and is likely to be useful with antibodies against a wide variety of substances. Several other immunocytochemical methods were found to be incompatible with DiI labeling. PMID- 2110210 TI - Genetically distinct cell populations in naturally occurring bone marrow-chimeric primates express similar MHC class I gene products. AB - The cotton-top tamarin (Saguinus oedipus) is a naturally occurring "A" + "B"--- "A" bone marrow-chimeric species. These primates usually are born as dizygotic twins and, due to placental vascular anastomoses, develop sharing each others' bone marrow elements. Strikingly, almost 50% of the PBL of a member of a twin pair are derived from the hematopoietic stem cells of its cotwin. To clarify the mechanisms underlying the maintenance of tolerance in these stable chimeras, MHC gene products have been biochemically characterized in cloned, genetically distinct, male and female lymphocytes from two male/female cotton-top tamarin twin pairs. Extensive MHC class II sharing between the genetically distinct cell populations was not seen in the two twin pairs. This was consistent with the MHC class II polymorphism seen in the species. However, the MHC class I gene products expressed by one member of a twin pair were almost identical to those expressed by its cotwin. A human minisatellite probe demonstrated restriction fragment length polymorphism in DNA from these animals, indicating extensive polymorphism. Thus, MHC class I sharing did not occur due to inbreeding in these animals. Additionally, another bone marrow-chimeric primate species, the common marmoset (Callithrix jacchus), expresses MHC class I molecules with low levels of variation. These studies suggest that the stable chimerism of bone marrow chimeric primates may be facilitated by MHC class I similarity between the genetically distinct bone marrow derived-cell populations in their circulation. PMID- 2110211 TI - Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation. AB - Sublethally irradiated mice undergo thymic regeneration which follows a phenotypic pattern of events similar to that observed during normal fetal development. Thymic regeneration after irradiation is the product of a limited pool of intrathymic radioresistant stem cells undergoing simultaneous differentiation. We show that in this model of T cell development, thymic regeneration follows a pathway in which the IL-2R is transiently expressed on CD4 /CD8- cells. IL-2R expression occurred during the exponential growth period of thymic regeneration, and IL-2R blocking prevented this explosive growth. Flow cytometry analysis revealed that the IL-2R blockade affected primarily the development of the immature CD3-/CD4-/CD8- (triple negative) cells and their ability to generate CD3+/CD4+/CD8+ or CD3+/CD4+/CD8- and CD3+/CD4-/CD8+ thymocytes. Thus, our findings demonstrate that blocking of the IL-2R resulted in an arrest in proliferation and differentiation by intrathymic radioresistant stem cells, indicating that the IL-2/IL-2R pathway is necessary for the expansion of immature triple negative T cells. PMID- 2110212 TI - Abnormalities of lymphokine gene expression in patients with common variable immunodeficiency. AB - Common variable immunodeficiency (CVI) is a syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and increased occurrence of both autoimmune disease and malignancy. In our study we examine the expression of lymphokine genes in mitogen-activated T cells from four patients with CVI. T cells from patients with CVI did not differ significantly from normals in total T cell number, CD4/CD8 ratio, CD45R expression, or proliferation in response to PHA. However, T cells from this group of patients did exhibit significant abnormalities of mitogen-induced lymphokine gene expression. T cells from patients exhibited significantly decreased expression of IL-2, IL-4, IL-5, and IFN-gamma when compared to normal controls. In contrast to these abnormal findings, mitogen-activated T cells from patients with CVI expressed normal amounts of IL-2R alpha and c-myc suggesting that these patients have a selective abnormality of T cell activation. Furthermore, it is likely that the deficient production of IFN-gamma by patient T cells is partially due to the abnormality of IL-2 production as the levels of IFN-gamma mRNA detected during the initial IL-2 independent phase of T cell activation were normal and the addition of exogenous rIL-2 was able to normalize IFN-gamma production by PHA-stimulated patient cells. Finally, supernatants from PHA-activated cultures of patients PBMC were deficient in their ability to support Ig secretion by Staphylococcus A Cowan's-activated normal B cells suggesting that these T cell abnormalities may contribute to the pathogenesis of this syndrome. PMID- 2110213 TI - Immunization of humans with polysaccharide vaccines induces systemic, predominantly polymeric IgA2-subclass antibody responses. AB - Ig class- and IgA subclass-specific immune responses to protein and polysaccharide Ag were studied in serum, external secretions, and at the single cell level in peripheral blood of systemically immunized adults. Immunization with tetanus toxoid induced predominantly IgG antibody responses in serum and in the PBMC. The IgA antibody response was low, and was mostly of the IgA1 subclass. In contrast, immunization with polysaccharide Ag (Haemophilus influenzae type b, Neisseria meningitidis serogroup A, C, Y, W-135, and Streptococcus pneumoniae capsular polysaccharides) elicited a major IgA response predominantly of the IgA2 isotype. Analysis of the molecular forms of secreted IgA antibodies indicated that polymers were produced early after immunization, irrespective of the nature of the Ag. When compared with serum antibody and to PBMC cell responses, systemic immunization with polysaccharides induced a minor salivary response dominated by IgG and IgM antibodies. In contrast, the presence of antipolysaccharide antibodies in bile, irrespective of their isotype, paralleled the serum response 14 days after the immunization with polysaccharide Ag. These results suggest that biliary Ig were mostly derived from serum. Different patterns of the expression of MHC class II Ag on T cells, B cells, and monocytes during the course of immunization with protein or polysaccharide Ag were observed: whereas protein Ag induced a high frequency of HLA-DP- and HLA-DR-expressing cells early in the course of immunization, polysaccharide vaccines elicited low and protracted increases of HLA-DP+ T cells. Polysaccharide vaccine covalently coupled to a protein carrier induced a higher frequency of antipolysaccharide antibody secreting cells in peripheral blood and increased the IgG to IgA ratio among polysaccharide-specific antibody-secreting cells. PMID- 2110214 TI - IL-6 functions as an exocrine hormone in inflammation. Hepatocytes undergoing acute phase responses require exogenous IL-6. AB - We have previously shown that IL-6 is the major monocyte- and fibroblast-derived regulator of acute phase protein gene expression and synthesis in hepatocytes in inflammation. Recently, we and others have shown that rat and human hepatoma cells express IL-6 mRNA, and the question arose as to whether normal hepatocytes express IL-6 and whether any such expression occurs under normal physiologic conditions or is seen in inflammation. Poly A+ mRNA of liver from normal rats and from rats undergoing an acute phase response was not positive when probed with cDNA for rat IL-6 under conditions in which macrophage mRNA was strongly positive. We then compared poly A+ mRNA from purified hepatocytes freshly isolated from normal rats--from rats that were undergoing an acute inflammatory response and from freshly isolated normal hepatocytes that had been cultured for 24 h in the presence or absence of dexamethasone (microM). Only the mRNA from normal hepatocytes cultured for 24 h in the absence of any glucocorticoid was obviously positive for IL-6. The increased expression of gamma-fibrinogen mRNA indicated the presence of inflammation. These results confirm the identification of IL-6 as an exogenous hormone for regulating normal hepatic acute phase protein synthesis in inflammation and rules out an autocrine mechanism being active in the liver in normal homeostasis. PMID- 2110215 TI - Human humoral immunity to hsp70 during Trypanosoma cruzi infection. AB - Immunologic screening of cDNA expression libraries has been widely used for the identification of DNA sequences encoding the immunologically relevant proteins of many pathogenic microorganisms. For reasons that are not entirely clear, sequences encoding 70-kDa heat shock and related proteins (hsp70), which are among the most highly conserved proteins known, have routinely been identified by this approach. Consequently, hsp70 proteins have been proposed to be involved in the autoimmune processes thought responsible for the pathogenesis of the diseases caused by some of these organisms, e.g., chronic Trypanosoma cruzi infection (Chagas' disease). Therefore, we investigated whether hsp70 might be a specific target of the human humoral immune response to T. cruzi infection, and, if so, whether humoral autoimmunity to hsp70 might play a role in pathogenesis. We found that hsp70 is indeed a major polypeptide Ag in Chagas' disease, but that the antibodies to T. cruzi hsp70 do not react with human hsp70--even though the proteins display 73% amino acid sequence identify. These results indicate that self-tolerance to hsp70 is maintained during chronic T. cruzi infection and strongly argue against a role for humoral autoimmunity to hsp70 in the pathogenesis of Chagas' disease. PMID- 2110217 TI - Estimation of D segment usage in initial D to JH joinings in a murine immature B cell line. Preferential usage of DFL16.1, the most 5' D segment and DQ52, the most JH-proximal D segment. AB - We established SPL2-1-2, a murine immature B cell line transformed by tsOS-59, a temperature-sensitive mutant of Abelson murine leukemia virus. SPL2-1-2 has a VHDJH-/G (germ-line) configuration, and can continuously generate D to JH joinings from the germ-line allele during culture. The D to JH joinings are strongly promoted by the shift of the culture temperature from permissive (35 degrees C) to non-permissive temperature (39 degrees C). Using this H chain gene rearrangement system, we succeeded in the estimation of the frequencies of D segment usage in initial D to JH joinings by deletion-mapping analysis. The results demonstrated the preferential utilization of DFL16.1, the most 5' D segment and DQ52, the most JH-proximal D segment in initial D to JH joinings. PMID- 2110216 TI - The regulation of resistance to Schistosoma mansoni by auto-anti-idiotypic immunity. II. Global qualitative and quantitative regulation. AB - These studies explore the suppression of resistance to schistosomiasis mansoni through interactions of autologous immune functions derived from an induced anti idiotypic response. This anti-clonotypic response is induced by immunization with syngeneic L3T4+ receptor-bearing lymphoblasts and for the sake of description is termed "auto-anti-idiotypic". It is antigenically restricted and cannot be induced by allogeneic cells. Anti-idiotypic immunization profoundly suppressed the development of protective immunity after exposure to irradiated cercariae and altered a wide variety of functional humoral and cellular immune responses to the parasite. In addition to quantitative suppressive effects, the anti-idiotypic network also regulated qualitative aspects of the immune response by increasing the heterogeneity and reducing the functional binding avidity of antibody for Ag. These effects also were reflected in analogous alterations in cellular reactivity, using the criteria of the Ag mediated blast transformation and delayed type hypersensitivity. Thus idiotypic regulation can mold the specificity and sensitivity of the immune response to Schistosoma mansoni by affecting quantitative and qualitative responses. Manipulation of idiotypic recognition provides an approach to optimize the expression of protective resistance to schistosomiasis. PMID- 2110218 TI - Specific immunoglobulins in schistosomiasis. AB - Specific and total immunoglobulins antibodies levels to Schistosoma antigens were determined in 44 patients with S. mansoni infection. No Significant increase was observed in parasitic specific IgG, IgM, and IgA levels in both acute and chronic infections. On the other hand, Significant increased specific IgE antibodies was demonstrated in both acute and chronic infections of bilharziasis. The results revealed that increased immunoglobulins was not Specific to Schistosomiasis infection. Also, No correlation was observed between clinical course of the infection and immunoglobulins levels. PMID- 2110219 TI - Correlation between circulating schistosomal antigen, schistosomal complement C3 and intensity of infection. AB - 53.7% of the already parasitologically proved schistosomiasis cases showed circulating schistosomal antigen (C.S.A.) in their sera with significantly higher levels than the controls, with no correlation between the level of C.S.A. and the foecal egg count. Significant higher levels of schistosomal complement C3 were found in schistosomiasis patients as compared to the control group, with no significant difference in the mean level of C3 between patients with positive and negative C.S.A. PMID- 2110220 TI - Correlation between intensity of infection and hepatic histopathological lesions in bilharzial patients. AB - Liver biopsy examination of 106 patients showed 47 with pure bilharzial liver, 16 with chronic persistent hepatitis, 19 with chronic persistent hepatitis associated with bilharzial liver, 14 with chronic active hepatitis and 10 with chronic active bilharzial liver. There was significant correlation between intensity of infection and bilharzial affection of the liver. PMID- 2110221 TI - Morbidity of schistosomiasis hematobia in an Egyptian village. AB - One hundred and fifty patients with active Schistosomiasis haematobium were chosen from Azizia village an endemic area. 50 healthy controls of the same age and sex groups were chosen. Patients were subjected to complete clinical and laboratory examination. Praziquantel orally in a dose of 40 mg/kg was given to each individual and its therapeutic efficacy was assessed by comparing the results of the previous investigations before and 3 months after treatment. The highest infection intensity was noticed in the small age group (A). There was a statistically significant increase of haematuria in this group, dysunia in middle age (B) and increase frequency of micturition & suprapubic tenderness in older age group (C). Ultrasonography showed partial calcification of bladder in 18% of cases in group A, 28% of cases in group B; in group C the percentage was 32% with 14% hydronephrosis, bladder mass 2%, stone bladder & ureter 6%. After praziquantel therapy there was a statistically significant (1) Reduction in haematuria, dysuria increase frequency and suprapubic tenderness (Z less than 1.96). (2) reduction of mean egg count in urine (3) significant improvement of Hb% (4) bladder calcifications showed partial improvement. PMID- 2110222 TI - The prophylactic and curative effect of oltipraz in experimental schistosomiasis mansoni in mice. AB - Effect of oltipraz on immature and mature forms of Schistosoma mansoni in mice experimentally infected with the Egyptian strain of the worms was assessed. The drug was administered to different groups of mice in a single oral dose of 750 mg/kg body weight 2 hours before infection, 7 days and 15 days after infection and in a single oral dose of 500 mg/kg body weight 30 days and 45 days after infection. Oltipraz was found to be active in reducing the number of worms significantly only when administered in a higher dosage 2 hours before infection and 7 days after infection. Thereafter, the parasites were refractory to the drug action until they have reached sexual maturity 45 days post-infection. PMID- 2110223 TI - Immunodiffusion, immunofluorescence and enzyme-linked immunosorbent assay in the serodiagnosis of giardiasis. AB - Circulating anti-Giardia lamblia antibodies have been estimated in the sera of 48 patients of parasitologically proven G. lamblia infection using the immunodiffusion (I.D.) indirect fluorescent antibody (I.F.A.) and enzyme-linked immunosorbent assay (ELISA) tests. The results showed that ELISA technique was the most simple, sensitive (95.8%) and specific (100%) test. These advantages make it more applicable in seroepidemiology of giardiasis. PMID- 2110224 TI - Oltipraz treatment in experimental schistosomiasis mansoni:VII. Effect of high dose oral therapy on alkaline phosphatase level in livers of infected mice. AB - Biochemical estimation of alkaline phosphatase (AP) in livers of mice experimentally infected with the Egyptian strain of S. mansoni before and after oltipraz treatment was carried out. The drug was given in a single oral dose of 500 mg/kg body weight. The results revealed that the drug led to gradual reduction in the AP mean level after 20 and 30 days from treatment. This was then followed by rise in the enzyme mean level, after 60 days. The drug also caused significant reduction in the AP mean level in livers of the drug control group of mice after 5 and 20 days from oltipraz administration in comparison normal uninfected controls. These findings might be attributed to a hepatocytotoxic effect of the drug. PMID- 2110225 TI - Application of enzyme-linked-immuno-electro-diffusion-assay (ELIEDA) in diagnosis of bilharziasis. AB - The sensitivity of the technique of immunoelectrodiffusion has been enhanced by combining it with an enzyme method. The precipitated immuno-complexes are treated with antibodies conjugated with an enzyme specific for each class of immuno globulins. This association realizes the ELIEDA and enable the class of immunoglobulins involved in the reactions to be determined. The technique allows the follow up and the qualitative evaluation of the bilharzial antibody in natural and experimental affections. PMID- 2110226 TI - Bilharzial role in staging bladder carcinoma histopathological-transurethral sonography and computerized tomography. AB - Bilharzial bladder tumour of 28 patients staged pre-operatively by transurethral ultrasound and computerized tomography (CT). The accuracy varied from 66.6% to 77.7% in different stages as compared with pathological stage. The bilharzial reaction could be play a role in this accuracy and the histopathological study is the accurate way to express the depth of infiltration of the tumour in the bladder wall as well as the depth of vascular invasion which may be greater than the primary tumour itself. PMID- 2110227 TI - Total leucocytic count, eosinophilia and cellular immune response in acute and chronic schistosomiasis. AB - Among school children in a rural area the serological diagnosis (ELISA) was more accurate than the parasitological tests. The mean total leucocytic and eosinophilic counts, and the blastogenic response to S. mansoni egg antigen were significantly higher in early than in chronic schistosomal cases. Blastogenic response to mitogens and S. mansoni adults preparation was insignificantly different. PMID- 2110228 TI - Effect of Altoside (ZR-515) on oxygen consumption, carbon dioxide out put and carbohydrate content of organophosphorus resistant strain of Musca domestica. AB - The effect of applying JHA ZR-515 at a concentration of 50 microliter/liter water in the larval rearing medium from the first larval instar on oxygen consumption, carbon dioxide out put and total carbohydrates was studied. The oxygen consumed by the pupae previously treated as larvae with ZR-515 was decreased and no adult could emerge. The carbon dioxide out put seems to follow a more or less the pattern of oxygen consumption. The concentration of total carbohydrate content in one day old pupae previously treated as larvae was significantly lower than normals. In three days old there was a marked significant increase and in five days old, the carbohydrate content was significantly higher than controls. PMID- 2110229 TI - Ultrastructure of the cyst wall of S. lindemanni with pathological correlations. AB - Electron microscopy of skeletal muscle biopsy from a case of human sarcocystosis revealed a new cyst type of S. lindemanni. The sarcocyst appeared large having a thick cyst wall with evident septa extending into the cyst and, characteristically, broad branched cauliflower like protrusions extending into the pericystic zone. This cyst type appeared to be highly pathogenic. In addition to the complete myofibrillar lysis of the infected muscle-fibre, there were delamination of the neighbouring myofibres, disruption of the sarcomeric orientation with dearrangement and bending oft he Z bands and loss of the T and L myofibrillar pattern in the pericystic zone. Features of myositis such as the presence of abundant lysosomal structures, myofibrillar disarray and glycogen formations were detected. These cytopathogenic signs were obviously attributed to the structural criterion of the cyst wall. The findings not only invalidate the concept that pathological conditions associated with human sarcocytosis are accidental, but also stress the value of electron microscopy in inducing relevant typing of sarcocysts on basis of their morphologically expressed pathogenic properties. PMID- 2110230 TI - Digyalum oweni, gen. nov., sp. nov., a new and unusual gregarin protozoan from the gut of mollusc Littorina obtusata (Prosobranchia: Gastropoda). AB - Digyalum oweni, gen. nov., sp. nov., is described from the gut of the gastropod mollusc Littorina obtusata. The gregarine has the unusual features of transverse orientation of the epicyte folds and two anterior pouch-like hollows. PMID- 2110231 TI - Intestinal helminthic and protozoal infections and urinary schistosomiasis in Egyptian children. AB - To extend information on the current distribution and frequency of parasitic infections in Egypt, one stool and one urine specimen from 2945 children, aged 6 to 12 years old were examined. The children were from 10 schools, one in Cairo, 2 in Giza Governorate, and 7 in the Nile delata. Frequency rates for S. mansoni by school were 0.3% in Cairo, 8-15% in Giza, and 3-79% in the delta; for S. haematobium, rates were 3% in Cairo, 25-71% in Giza, and 0-33% in the delta. Rates for strongyloidiasis, trichuriasis, and trichostrongliasis were low in each location never exceeding 1%. Frequency rates for ascariasis were 3-31%, ancylostomiasis 3-8%, enterobiasis 2-22%, hymenolepiasis 4-20%, amebiasis 13-52%, and giardiasis 5-25%. F. hepatica infections (0.01%) were found in Sobtas, and an 8% H. heterophyes infection rate was found in Mataryia. PMID- 2110232 TI - [Preventive measures against infectious diseases brought back to Japan from abroad and caused by imported foods]. PMID- 2110233 TI - [Various infections in the aged and therapeutic problems]. PMID- 2110234 TI - [Diagnosis and prevention of non-A, non-B viral hepatitis]. PMID- 2110235 TI - [New diagnostic standards in rheumatoid arthritis and recent trends in drug therapy]. PMID- 2110236 TI - [Diagnosis and treatment of acute kidney failure]. PMID- 2110238 TI - Long-term reductions in GH, insulin-like growth factor-I and body weight gain in rats treated neonatally with antibodies to rat GH. AB - Treatment of neonatal rats on days 2-5 with antibodies against rat GH (rGH) markedly reduced body weight gain and serum concentrations of insulin-like growth factor-I for 6-8 weeks in both females and males, after which weight gain normalized without evidence of catch-up growth. There were no significant effects on serum prolactin, tri-iodothyronine or corticosterone. Testis and ovarian weights were reduced, although only in proportion to body size. In females, but not males, the treated rats, though lighter, had increased fat deposition in the parametrial depot. Pituitary weight was considerably reduced over 100 days later, as was the pituitary content of GH, but not prolactin. The response to GH releasing factor of both male and female rats was also greatly reduced at this time. Taken together with the fact that these rGH antibodies can bind directly to somatotrophs, we propose that the long-term effects of the antibodies are induced by specific somatotroph destruction. PMID- 2110237 TI - Regional cholesterol screening: problems and potentials. AB - Mass cholesterol level screening was carried out in 3,288 individuals. Over a wide range of ages, moderate or high risk values were found in 16%. Follow-up of those with abnormal cholesterol levels revealed that a low percentage visited their family physicians. Moreover, successful responses to treatment were identified in a very small number. The cost of lowering an elevated serum cholesterol level identified in this manner was approximately $800. Problems and potentials of this approach are discussed. Interest in serum cholesterol level control and understanding of its importance have greatly increased. Patients and physicians have become more well informed as a result of the Lipid Research Clinics-Coronary Primary Prevention Trial (LRC-CPPT) and recent guidelines proposed by the National Heart Lung and Blood Institute (NHLBI). As a result of these reports, it is now recognized that lowering an elevated cholesterol by 1% causes a 2% reduction in mortality from coronary artery occlusive disease. Moreover, it is now conceded that normal levels are much less than had been thought previously and it is recommended that all adults receive treatment to maintain a serum cholesterol less than 200 mg/dl. We were recently invited to present an exhibit in the high technology area of the Kentucky State Fair. This provided an opportunity to develop and test the mass screening process, collect data, and to evaluate the cost-effectiveness of such screening processes. PMID- 2110239 TI - Effects of bovine 35 kDa FSH-suppressing protein on FSH and LH in rat pituitary cells in vitro: comparison with bovine 31 kDa inhibin. AB - The mode of action of a recently isolated gonadal protein, termed FSH-suppressing protein (FSP) or follistatin, on basal and gonadotrophin-releasing hormone (GnRH) stimulated release of FSH and LH and on pituitary cell content of FSH and LH was examined in rat pituitary cell cultures and compared with the previously reported effects of inhibin. Pituitary cells were cultured for 3-9 days in the presence of graded doses of FSP and the basal release rates and changes in cell contents of FSH and LH determined during this period. FSP suppressed both the basal release rate and the cell content of FSH with median inhibitory concentrations (IC50) of 135 and 161 pmol/l respectively. The corresponding effects of FSP on LH basal release rate and LH cell content (IC50 = 200 pmol/l) were limited compared with the effects on FSH. The effect of FSP on GnRH-stimulated release of FSH and LH during 4 h was determined in cells which had been preincubated with FSP for 3 days, and the GnRH-stimulated release of FSH and LH analysed as a percentage of the respective gonadotrophin available for release. FSP antagonized GnRH action with dose-related increases in the GnRH median effective (stimulatory) concentrations for FSH and LH release (EC50 values = 56 and 400 pmol/l respectively) and a suppression in the maximum release of FSH and LH by excess GnRH (IC50 values = 142 and 150 pmol/l respectively). The effect of FSP on FSH cell content after 3 days in culture was insensitive to the neutralizing effects of an inhibin antiserum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110240 TI - Gonadotrophin-binding components in porcine follicular fluid. AB - The follicular fluid is an important milieu for the growing and maturing oocyte and granulosa cells. In this study we investigated: (1) the properties of gonadotrophin-binding sites in the supernatant fraction of porcine follicular fluid (pFF) and compared them with those of membrane-bound receptors, and (2) the relative changes that occur in pFF and granulosa cell receptor-binding activity following hormone priming of gilts. 125I-Labelled human chorionic gonadotrophin (hCG) and 125I-labelled ovine FSH (oFSH) binding to particulate and supernatant fractions of pFF were hormone-specific and saturable. The concentration of 125I labelled hCG-binding sites was roughly 50-fold higher in particulate than in supernatant fractions of pFF. However, 30-40% of the total 125I-labelled hCG binding activity in pFF was present in the supernatant fraction of commercial batches of pFF. 125I-Labelled oFSH binding to pFF membranes was markedly higher than to supernatant fractions. Binding of 125I-labelled hCG and 125I-labelled oFSH to granulosa cells and supernatants of pFF showed a time-dependent variation in response to hormone priming. The results suggest that gonadotrophin-binding sites in the supernatant fraction of pFF have properties similar to those of their membrane-bound counterparts. 125I-Labelled hCG-binding activity in the supernatant fraction of pFF was shown to be more stable than detergent solubilized LH/hCG receptors, even in glycerol-preserved preparations. Based on a number of criteria, we have speculated that pFF may have components which may be similar in structure to the extracellular domain of the LH/hCG receptor. PMID- 2110241 TI - Molecular cloning and characterization of the structural gene for the major iron regulated protein expressed by Neisseria gonorrhoeae. AB - This report describes the cloning and sequencing of the major iron-regulated protein (termed Fbp) of Neisseria gonorrhoeae strain F62. Attempts to identify recombinants expressing the Fbp using specific antibody proved unsuccessful. Therefore, an alternative cloning strategy using oligonucleotide probes derived from NH2-terminal and tryptic fragments of this protein was used to identify short fragments of the gene. Using this methodology, the gene encoding the precursor of Fbp was cloned on three separate overlapping fragments and sequenced, and the amino acid sequence was deduced. These data were unambiguously confirmed by the known NH2-terminal amino acid sequence and were supported by the sequences from tryptic fragments that lie outside of this region. Using oligonucleotide probes, we were unable to obtain clones encoding the potential regulatory region of this protein. Therefore, the technique of inverse polymerase chain reaction was used to amplify a fragment containing an additional 200 bp. This fragment was cloned and sequenced and found to contain a consensus ribosome binding site and potential -10 and -35 sequences. Hybridization analysis of genomic DNA from gonococcal strain F62 indicated that only a single copy of the Fbp gene exists per genome. These results complement the biochemical characterization of the Fbp expressed by gonococci and further suggest that it has a role in iron-acquisition. PMID- 2110242 TI - Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin. AB - Bovine insulin(BI)-specific I-Ab-restricted T cell clones have been characterized for fine specificity and TCR gene usage. We have demonstrated that mouse strains carrying H-2b on three different genetic backgrounds (C57BL, BALB, and 129) rearrange and express the V beta 6 gene in a large proportion (36%) of insulin specific clones. In these strains, the non-MHC background did not seem to influence TCR gene usage in response to BI. The V beta 6+ clones appeared to be selected by the antigen. In contrast, no V beta 6+ clones could be isolated from (B6 x DBA/2)F1 mice, where V beta 6+ (and V beta 8.1+) T cells are deleted by self tolerance to Mls-1a. Thus, although a small proportion of residual V beta 6+ cells had been demonstrated in Mls-1a mice, these cells could not be retrieved in a response that uses V beta 6 predominantly. In functional terms, therefore, the deletion of V beta 6 by self tolerance appears to be complete. Instead of V beta 6, the majority (up to 60%) of I-Ab- as well as I-Ad-restricted insulin-specific clones from the (B6 x DBA/2)F1 mice expressed V beta 8.2 and V beta 8.3. This shift of gene usage was not accompanied by any detectable change in the fine specificity pattern of response. Thus, in the insulin-specific response, the flexibility of T cell repertoire fully compensates for deletions caused by self tolerance. PMID- 2110245 TI - In-vitro activity of ampicillin/sulbactam and other antibiotics against clinical isolates of Haemophilus sp. and Branhamella catarrhalis. AB - The ampicillin/sulbactam combination is one of several such drug combinations of a beta-lactam and suicide inhibitor having a wide spectrum of activity. These characteristics induced us to evaluate the in vitro activity of this combination towards 54 strains of Haemophilus sp. (38 beta-lactamase producers) and 20 strains of Branhamella catarrhalis (16 beta-lactamase producers). All strains were isolated from sputum, sinusal aspiration and tympanocentesis. In the case of Haemophilus sp beta-lactamase producers, minimal inhibitory concentrations of ampicillin were reduced 8 times by the use of the inhibitor; good results were also obtained for B. catarrhalis. Haemophilus influenzae, B. catarrhalis together with Streptococcus pneumoniae are recognized as the major pathogens involved in upper respiratory tract infections. The increasing frequency of beta-lactamase producing strains has impaired the use of aminopenicillins. The combination of an inhibitor and beta-lactam restore the activity of the latter, suggesting that this combination can serve as first choice in therapy. PMID- 2110244 TI - Expression and role of p75 interleukin 2 receptor on human monocytes. AB - We investigated the expression of IL-2R subunits in human monocytes using the TU27 mAb, which recognizes the p75 chain, and anti-Tac mAb, which recognizes the p55 moiety of the IL-2R. We found that p75 but not p55 is constitutively expressed in more than 90% of fresh human monocytes. Antibody to p75, but not to p55, inhibited the activation of monocytes to a cytotoxic stage induced by IL-2 but did not block IFN-gamma-induced cytotoxicity. Our data demonstrate that the p75 chain is expressed on human monocytes and is involved in the activation of monocytes by IL-2. PMID- 2110243 TI - Eleven distinct VH gene families and additional patterns of sequence variation suggest a high degree of immunoglobulin gene complexity in a lower vertebrate, Xenopus laevis. AB - Lower vertebrate species, including Xenopus laevis, exhibit restricted antibody diversity relative to higher vertebrates. We have analyzed more than 180 VH gene containing recombinant clones from an unamplified spleen cDNA library by selective sequencing of JH and CH positive clones following iterative hybridization screening with family-specific VH probes, 11 unique families of VH genes, each associated with a unique genomic Southern blot hybridization pattern, are described and compared. Considerable variation in the number of hybridizing components detected by each probe is evident. The nucleotide sequence difference between VH families is as great as, if not more than, that reported in other systems, including representatives of the mammalian, avian, and elasmobranch lineages. Some Xenopus Ig gene families encode alternative amino acids at positions that are otherwise invariant or very rarely substituted in known Igs. Furthermore, variations in complementarity determining region sequences among members of the same gene family and high degrees of DH and JH region complexity are described, suggesting that in at least this lower vertebrate species, the diversity of expressed Ig VH genes is not restricted. PMID- 2110246 TI - Improved sectioning and ultrastructure of bacteria and animal cells embedded in Lowicryl. AB - Lowicryl K4M-embedded Gram-positive and Gram-negative bacteria have a tendency to separate between the cell surface and the resin. This often leads to distortion of bacteria and more especially of mycobacteria. We describe attempts made to overcome this technical problem. Different assays were made on Bacillus subtilis, Escherichia coli, and Mycobacterium avium: 1) Modification of the bacterial surface by coating of bacteria with proteinic compounds; 2) treatment of bacteria with metallic salts known to modify cell wall polysaccharides; and 3) comparison between Lowicryl K4M and HM20. Conditions have been found in which the separation of all bacterial species from the resin is abolished. The most important factor appeared to be the treatment of bacteria before dehydration, with 0.5% uranyl acetate for 30 min. The second most important factor, especially for M. avium and to a lower extent for Gram-negative bacteria, was the use of Lowicryl HM20. No differences were observed with Gram-positive bacteria between K4M and HM20. Pre embedding in gelatin instead of agar improved sectioning of M. avium, but had no effects on the other bacterial species. These conditions applied to macrophages infected with Shigella dysenteriae or M. avium also gave excellent results. In addition to sectioning improvement of bacteria, uranyl acetate improved the ultrastructure of bacteria and macrophages. All organelles were more clearly delineated and, hence, more easily identified. Finally, it was shown that UA treatment did not affect immunogold labeling of a variety of antigens. PMID- 2110247 TI - Comparison of osmium/sonication and EDTA/sonication microdissection techniques in exposing the adepithelial basal lamina surface of developing rat colon. AB - We have used two epithelial-stripping techniques in our studies of the basal lamina in the developing rat colon. The first involves prolonged osmication followed by sonication; the second uses chelation of calcium by EDTA followed by sonication. Both techniques remove the epithelium from the basal lamina; however, the EDTA/sonication technique appears to produce a cleaner adepithelial surface of the basal lamina. In addition, the fine structure of the basal lamina appears to be better preserved in specimens prepared by the EDTA/sonication technique. In contrast, the basal lamina of specimens prepared by the osmium/sonication technique had a shattered appearance that we believe is due to an increase in the fragility of the delicate fetal basal lamina. PMID- 2110248 TI - [Reactions and interactions of drugs]. PMID- 2110249 TI - Photoreceptor-specific efficiencies of beta-carotene, zeaxanthin and lutein for photopigment formation deduced from receptor mutant Drosophila melanogaster. AB - Drosophila rearing media had only beta-carotene, zeaxanthin or lutein as precursors for photopigment chromophores. Zeaxanthin and lutein are potentially optimum sources of the 3-hydroxylated retinoids of visual and accessory photopigments. Mutants made the electroretinogram in white (w) eyes selective for compound eye photoreceptors R1-6, R7 and R8: R1-6 dominates w's electroretinogram; R7/8 generates w;ora's (ora = outer rhabdomeres absent); R8 generates w sev;- ora's (sev = sevenless). Microspectrophotometry revealed R1-6's visual pigment. In w, all 3 carotenoids yielded monotonic dose-responses for sensitivity or visual pigment. An ultraviolet sensitivity peak from R1-6's sensitizing pigment was present at high but not low doses. In w;ora, all 3 carotenoids gave similar spectra dominated by R7's high ultraviolet sensitivity. For w sev;ora, all spectra were the shape expected for R8, peaking around 510 nm. The sensitivity dose-response was at its ceiling except for low doses in w;ora and zero supplementation in w sev;ora. Hence, without R1-6, most of our dose range mediated maximal visual pigment formation. In Drosophila, beta-carotene, zeaxanthin and lutein mediate the formation of all major photopigments in R1-6, R7 and R8. PMID- 2110250 TI - Reactance. Understanding aggressive behavior in long-term care. PMID- 2110251 TI - There's the forest. The object lesson of NSAID "gastropathy". PMID- 2110252 TI - Prospective two-year followup of recombinant interferon-gamma in rheumatoid arthritis. AB - Seventy patients with rheumatoid arthritis (RA) completing a 12-week multicenter double blind trial comparing recombinant human interferon-gamma (r-IFN-gamma) with placebo were enrolled in a longterm prospective protocol evaluating r-IFN gamma in RA. Forty (57%) patients after 1 year and 26 (37%) patients after 2 years continued the drug with sustained clinical benefit. Over 2 years, r-IFN gamma was discontinued in 44 patients (lack of efficacy--25, withdrawn consent- 7, noncompliant--4, suspected adverse drug reactions--2, concurrent illness--6). Two years of treatment with r-IFN-gamma were well tolerated with sustained clinical benefit in some patients with few significant adverse drug reactions. PMID- 2110253 TI - Psoriatic arthritis and myopathy. AB - We describe a patient with psoriatic arthritis and a myopathy. The myopathy did not follow the time course of topical steroid treatment, nor did the patient display any features of hypercorticolism or local steroid excess. No evidence was found to support the diagnosis of polymyositis. Psoriatic myopathy is an uncommonly described condition. Steroid induced myopathy shares some nonspecific features with psoriatic myopathy, but can be differentiated by the clinical response to cessation of steroid therapy. Myalgia and 24 h urine creatine elevation are 2 features not previously described in association with psoriatic myopathy. The latter appears to correlate with muscle weakness and may be useful in following the course of this disease. PMID- 2110254 TI - Tuberculous arthritis. Report of a case with multiple joint involvement and periarticular tuberculous abscesses. AB - We describe a 41-year-old man with an unusual presentation of tuberculous joint disease involving 3 peripheral joints: right knee, wrist and first metatarsophalangeal. Periarticular "cold" tuberculous abscesses were observed in the ulnar aspect of his right hand and on the lateral aspect of his first right metatarsal bone. Mycobacterium tuberculosis was isolated from his knee and both abscesses. Synovial biopsies taken from these 3 joints showed typical tuberculous granulomata. M. tuberculosis was also isolated from 3 urine samples. Neither immunodeficiency, or a predisposing condition for tuberculosis could be demonstrated. Combined surgical and antibiotic treatment was effective. PMID- 2110255 TI - Retirement and later health problems. PMID- 2110256 TI - Nutrition in the older hospital patient. AB - The importance of nutrition in the treatment of the older hospital patient has often been underestimated. This may be because of a failure to recognize the special nutritional problems of this age group. It is important to recognize that the older patient is more likely to be admitted to hospital suffering some degree of malnutrition and the nutritional consequences of the metabolic response to trauma may be more severe in this group. More attention needs to be placed on nutritional requirements and nutrient provision during rehabilitation. Adverse nutritional consequences of illness may be prolonged in the older subject and an extended period of nutritional supplementation may be required to produce benefit. It should be emphasized that adverse clinical consequences of nutritional deficit, and advantages of nutritional support, may not be evident in the short term. Long term follow up of nutritionally disadvantaged patients, and patients who have received specialized forms of nutritional support, will be required if the true contribution of nutrition to clinical outcome is to be evaluated. PMID- 2110257 TI - Indoor tanning--physiological abnormalities induced by ultraviolet-A. PMID- 2110258 TI - Prescribing practices and patient sex differences. PMID- 2110259 TI - The diets of British schoolchildren. PMID- 2110260 TI - Phases of community care in health and social services. PMID- 2110261 TI - Dental health education for the visually impaired child. PMID- 2110262 TI - Comparison of phenothrin shampoo and malathion lotion in the treatment of head louse infection. AB - Eighty patients (age range 4-10 years) with head lice infection were recruited to the study. Forty patients were treated with a single application of 0.2% w/v phenothrin liquid shampoo and 40 with 0.2% w/v malathion lotion. Inspection of the patients one week later revealed that no live lice remained in either group, but that two patients had viable eggs in the malathion lotion group. Re inspection four weeks after application revealed that five patients of the phenothrin shampoo group and seven of the malathion lotion group had viable eggs. Live lice were not seen to be present in either treatment group. The results indicate that both products are effective in the treatment of head lice infection and that the phenothrin shampoo would be a useful addition to the insecticides currently employed. PMID- 2110263 TI - Growth patterns in Saudi Arabian children. AB - The measurements of head and chest circumferences of 6623 Saudi Arabian pre school children are presented for the first time. The data were collected through a large scale cross-sectional growth study carried out in Riyadh, the capital of the Kingdom of Saudi Arabia. The results indicate that the average head and chest circumference measurements of the girls were smaller than the boys in all age groups. The analysis of variance results confirmed that these differences were statistically significant. The date indicated that among the average-build (the 50th centile) pre-schoolers, the head circumference measurements of the newborns were larger than the chest circumference measurement by 4.5%. By one year of age, these measurements were equal. After one year, the chest circumference grew larger than the head circumference. However, among the small-build preschoolers (the 3rd centile), the chest circumference measurements did not reach the head circumference measurements until nearly 30 months after birth. PMID- 2110264 TI - Trauma patients in an Indian hospital. AB - The study was carried out at the Emergency Department of Jawaharlal Nehru Medical College Hospital, Aligarh Muslim University, Aligarh, India, to ascertain the pattern of trauma in the patients. A total of 2446 trauma cases were recorded in the year 1987. Accidental falls were the commonest cause of injury, i.e 35.7%, followed by motor-vehicle collisions (23.5%), pedal cyclists (8%), occupational injuries (5.2%) and sports injuries (5.2%). The commonest age group involved was 5-15 years which accounted for 32.8% of all trauma. Fractures (44%) were the most frequently observed nature of injury. Death due to trauma was highest in motor vehicle collisions (31%) followed by accidental falls (16%), and occupational injuries (12%). PMID- 2110265 TI - Control of foodborne and waterborne diseases: position paper for Scotland. PMID- 2110266 TI - Density, location, and sampling of Sarcoptes scabiei (Acari: Sarcoptidae) on experimentally infested pigs. AB - Forty-eight weaned pigs were inoculated with 0 (controls), 100 (low dose), and 1,000 (high dose) itch mites, Sarcoptes scabiei (De Geer), and allowed to develop infestations for up to 10 wk. Pigs were slaughtered in sequence during the experiment to sample hides and count mites through potassium hydroxide digestion. Incipient crusted lesions occurred in ears of 4 of 16 low-dose pigs and 7 of 16 high-dose pigs, averaged less than 3 cm2 in area, and contained 86% of all females and 87% of all other mite stages found on those pigs. Crusts aside, faces had the highest mite densities among six body regions in both infested groups. Overall, high-dose pigs had higher mite populations (269 compared with 39 mites on low-dose pigs), although values were not significantly different (P = 0.13). Mite populations did not grow significantly during the 10 wk, but variance increased among pigs in each dose group. A hide-sampling plan derived from these data indicates whole-body populations could be estimated by censusing only the crusts, if present. If absent, sampling mites from the face and dorsum should provide acceptable estimates of whole-body totals of females and other stages. A sample size of 13 hides from a herd will yield an estimate of mean whole-body total with a 90% CI less than or equal to 50% of the estimated mean. PMID- 2110267 TI - Enhanced malignant conversion of benign mouse skin tumors by cisplatin. AB - The chemotherapeutic agent cisplatin, reported to be a complete carcinogen in rodents and a tumor initiator for mouse skin, was tested for activity to enhance the conversion of carcinogen-induced skin papillomas to carcinomas. Initiation of mouse skin by 7,12-dimethylbenz[a]anthracene followed by 12 weeks of promotion by 12-O-tetradecanoylphorbol-13-acetate produced seven to eight papillomas/mouse. Ten weekly injections of 100 micrograms of cisplatin into these papilloma-bearing mice induced a 2.3-fold enhancement of conversion relative to the spontaneous rate of 1.9%. Even a single exposure to cisplatin in tumor-bearing mice increased the carcinoma incidence to the same extent as 10 exposures to urethane, an agent previously shown to enhance malignant conversion. At the dose tested, cisplatin was inactive as a complete carcinogen or a tumor promoter. Cisplatin-DNA adducts, measured in samples from skin, liver, and kidneys, were persistent for at least 4 weeks after the last exposure to cisplatin. Thus cisplatin is a relatively potent inducer of the putative genotoxic changes required for conversion of skin tumors from a benign to a malignant phenotype. The activity of cisplatin in the initiation and malignant conversion stages in this animal model for carcinogenesis suggests that patients given cisplatin-based chemotherapy are at increased risk for the development of treatment-induced second cancers. PMID- 2110268 TI - Effect of nicotine on 7,12-dimethylbenz[a]anthracene carcinogenesis in hamster cheek pouch. AB - We divided 40 male Syrian golden hamsters into four groups of 10 animals each, and we treated both cheek pouches of each hamster three times a week as follows: group 1, 50 microL of sesame oil; group 2, 50 microL of 6% nicotine in sesame oil; group 3, 50 microL of 1% 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil; and group 4, 50 microL of 1% DMBA in 6% nicotine in sesame oil. Cheek pouches were examined clinically and histologically after 12 weeks of treatment. Hamsters treated with DMBA and nicotine showed significantly (P less than .001) more tumors and a significantly (P less than .05) greater-than-expected proportion of large tumors (greater than or equal to 3-mm diameter) than hamsters treated with DMBA alone. Histologically, there was a greater degree of dysplasia in lesions from the group receiving DMBA plus nicotine than in the DMBA only group. The results suggest that nicotine acts as a cofactor in DMBA tumorigenesis. PMID- 2110269 TI - Controlling the hemorrhage of routine coagulation tests. PMID- 2110271 TI - Intravenous recombinant tissue-type plasminogen activator in patients with acute myocardial infarction--a report from the multicenter thrombolysis trial. AB - The efficacy and safety of intravenous infusion of human tissue-type plasminogen activator (rt-PA), developed in Japan (TD-2061), were investigated in 205 patients (154 men and 51 women) with evolving myocardial infarction (EMI). TD 2061 was given at a rate of 3.2 to 50 mg over 1 h after angiographic documentation of complete or subtotal (99%) occlusion. Nineteen patients were excluded as they did not meet the inclusion criteria. A total of 186 patients were divided into 6 groups according to the total dose given: Group I, 3.2 mg, 10 patients (pts); Group II, 6.4 mg, 15 pts; Group III, 12.8 mg, 15 pts; Group IV, 25.6 mg, 38 pts; Group V, 33.3 mg, 70 pts; Group VI, 50.0 mg, 38 pts. Ages ranged from 30 to 70 years (mean 60 +/- 1). Coronary angiography was done at 30 min and 1 h. In patients with TIMI grades 0 and 1, reperfusion was accomplished after 1 h in 22% of Group I, 50% of Group II, 64% of Group III, 70% of Group IV, 67% of Group V, and 74% of Group VI patients. Complications were hypotension, nausea and vomiting, bradycardia and bleeding at the puncture site. These findings suggest that clot-selective coronary thrombolysis can be induced in patients with EMI by means of human tissue-type plasminogen activator without concomitant induction of a severe systemic lytic state. The optimal dose for Japanese patients is considered to be 33.3-50.0 mg from the standpoint of reperfusion. PMID- 2110270 TI - Reevaluation of serum-plasma differences in total cholesterol concentration. AB - We measured total cholesterol levels in serum and disodium ethylenediaminetetraacetate (EDTA) plasma samples obtained from 84 healthy medical students during their entrance physical examinations and 48 adults from a cholesterol screening program who were resampled because they had initial values of 5.17 mmol/L (200 mg/dL) or higher. Plasma cholesterol concentrations were 4.7% lower than those in serum samples. The plasma and serum values were highly correlated (r = .994), however, suggesting that measurements in EDTA plasma can be converted readily to equivalent serum concentrations. Thus, the negative bias in EDTA plasma was greater than the 3% value cited in the National Cholesterol Education Program Guidelines, probably because the amount of EDTA now provided in evacuated blood collection tubes is 50% greater than in those used when the 3% value was established. These findings are relevant to the interpretation of both cholesterol screening measurements and follow-up lipoprotein analyses. PMID- 2110272 TI - Diuretic effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) in anesthetized rats. AB - A synthetic amino acid, L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), can be converted to (-)-norepinephrine (NE) by aromatic L-amino acid decarboxylase (AADC) in various mammalian tissues. Recent studies have indicated the pressor and diuretic effects of L-threo-DOPS. In this study, we examined the effects of L threo-DOPS on renal hemodynamics and function in anesthetized rats, and evaluated possible mechanisms of the diuresis. Intravenous infusion of L-threo-DOPS at 120 micrograms/kg/min exerted a significant increase in mean arterial pressure (MAP). There was a slight but nonsignificant decrease in renal blood flow (RBF). Although the glomerular filtration rate (GFR) remained at a constant level, urine flow (UF) and urinary sodium excretion (UNaV) increased significantly during the drug infusion. Pretreatment with AADC inhibitor, benserazide, completely blocked both the pressor and diuretic effects of L-threo-DOPS. When the renal perfusion pressure was protected from the pressor effect of the drug by using a Blalock clamp, the drug-induced diuresis was abolished. The diuretic effect of L-threo DOPS was markedly attenuated by the administration of phentolamine. There was a positive correlation between plasma NE concentration and UF during the infusion of L-threo-DOPS. Intrarenal arterial infusion of L-threo-DOPS at 20 micrograms/kg/min was without effect on renal function. These results indicate that diuresis and natriuresis induced by L-threo-DOPS are dependent on the pressor effect of NE via peripheral alpha-adrenoceptor activation. PMID- 2110273 TI - Ca2(+)-dependent and independent mechanisms of sustained contraction in vascular smooth muscle of rat aorta. AB - Norepinephrine (NE), prostaglandin F2 alpha (PG), 12-deoxyphorbol 13-isobutyrate (DPB) and high K+ induced sustained increase in cytosolic Ca2+ [( Ca2+]i) and muscle tension in rat aorta. Verapamil, at the concentration which abolished the high K(+)-induced changes, also abolished the increase in [Ca2+]i due to NE, PG and DPB although contractions were only partially inhibited. Excess EGTA further decreased [Ca2+]i although a part of the contraction was not inhibited. These results indicate that the sustained contractions induced by NE, PG and DPB are due to increase in [Ca2+]i, increase in Ca2+ sensitivity of contractile elements, and a Ca2(+)-independent mechanism. PMID- 2110274 TI - [Incidence of pathologic ammonia concentrations in the plasma in children with seizure disorders treated with Convulsofin/Convulex and other anticonvulsants in comparison with children with brain damage and healthy children]. AB - In healthy children plasma ammonia concentrations show values from 12.3 to 57.2 mumol/l (80%-range) (group I). We also measured plasma ammonia in epilepsy patients with valproate therapy (group II) and epilepsy patients treated with other anticonvulsiva (group III). In a fourth group there were children with various cerebral lesions without episodes and without anticonvulsiva therapy. There were significant differences between group I and group II and group II and group IV respectively. But no significant differences were found between the patients who were treated with valproate and the patients with cerebral lesions. The data does not allow the plasma ammonia concentration to be taken as a control parameter in children treated with valproate. Ammonia estimation at the beginning of therapy, however, may be used as risk indicator. PMID- 2110276 TI - Pancreas transplantation at Mayo: I. Patient selection. AB - From October 1987 to December 1988, 59 patients underwent assessment for combined kidney and pancreas transplantation or pancreas transplantation after receiving a kidney allograft. We report our criteria for accepting candidates for transplantation, the results of the selection process, and the clinical and laboratory profile of those patients who underwent transplantation. Of the overall group, 22 patients (37%) were approved medically, 3 of whom were awaiting financial approval. Of the 59 patients, 15 (25%) were not approved for the transplantation program for medical reasons; in addition, 16 patients declined participation and 3 were not accepted because of lack of financial resources. Medical reasons for exclusion from pancreas transplantation were coronary artery disease in six patients, severe peripheral vascular disease in six patients, other medical problems in two patients, and noncompliance in one patient. Thus, many patients who underwent assessment for pancreas transplantation did not enter the program because of medical, financial, or personal preference reasons. In most cases, the medical reason for exclusion from pancreas transplantation was a cardiovascular disorder. PMID- 2110275 TI - Measurement of cerebral glucose utilization from brain uptake of [14C]2 deoxyglucose and [3H]3-O-methylglucose in the mouse. AB - Glucose utilization (GU) in the mouse brain in vivo was measured by the simultaneous use of [14C]2-deoxyglucose (2DG), the glucose analogue that can be phosphorylated in the brain, and [3H]3-O-methylglucose (3MG), the nonmetabolizable glucose analogue. Originally, this method was developed by Gjedde et al. (1985) in the rat and in humans. The present study examined the validity of this method in the mouse brain. The effects of urethane and pentobarbital (PB) on GU were also studied. Whereas the distribution volume of 3MG reached a constant value under each condition after 10 min of the tracer circulation, the apparent volume of distribution of 2DG, which increased with time in the awake mice, did not increase so greatly in the anesthetized and hypothermic mice, indicating that the net rate of 2DG phosphorylation is lowered under these conditions. These data were fitted for the conventional three compartmental model and the values of rate constants of influx (K1), efflux (k2), phosphorylation, and dephosphorylation for 2DG, and K1 and k2 for 3MG were computed by nonlinear least square regression method. No significant difference in the value of K1/k2, the distribution volume of the precursor pool, was observed between 2DG and 3MG, indicating that 3MG can be used to estimate the distribution volume of unmetabolized 2DG in the brain. The values of GU calculated from the values of estimated parameters were not significantly different from those calculated from blood and tissue radioactivities obtained during 10 min after the injection of the tracers in both awake and PB anesthetized mice. These findings indicate that the double tracer technique is useful for measuring GU in a short duration experiment. PMID- 2110277 TI - [Ascites in metastatic neuroendocrine tumor of the intestine. Cytologic and immunocytochemistry diagnosis]. AB - The presence of neuroendocrine tumor cells in ascites is extremely rare. Cytologic specimens of ascites of two patients suffering from this tumor disease were examined. The use of immunocytochemical staining allows to reach a correct diagnosis in cases in which the result of conventional diagnosis remains unsettled. PMID- 2110278 TI - Potential participation of calpain in platelet activation studied by use of a cell penetrating calpain inhibitor (calpeptin). AB - Employing a cell penetrating calpain inhibitor (calpeptin), the role of calpain in platelet activation was examined. In washed platelets (WPs) both thrombin and collagen-induced platelet aggregation were dose-dependently inhibited by calpeptin. The addition of plasma to WPs interfered with the action of calpeptin, however more than 3 min preincubation of calpeptin with WPs completely abolished the influence of plasma. In thrombin-activated WPs with calcium, the increase of intracellular calcium concentration, [Ca2+]i, and the production of inositol triphosphate (IP3) were dose-dependently inhibited by calpeptin. The generation of thromboxane B2 (TxB2) was inhibited by calpeptin in collagen and thrombin activated WPs. In [3H]-arachidonic acid (AA)-labelled platelets, calpeptin increased the amount of [3H]-AA liberated by inhibiting [3H]-AA degradation after collagen or thrombin stimulation. When [14C]-AA degradation by the platelet suspension was observed, calpeptin inhibited TxB2 and hydroxyheptadecatrienoic acid (HHT) generation but increased prostaglandin (PG) E1, E2, 12 hydroxyeicosatetraenoic acid (12HETE) and AA. Based on these findings, calpain may be involved in the activation phospholipase C and thromboxane synthetase. PMID- 2110279 TI - Testicular weight, tubular diameter and number of Sertoli cells in rats are decreased after early prepubertal administration of an LHRH-antagonist; the quality of spermatozoa is not impaired. AB - To suppress gonadotropin secretion during the sensitive period in development of the testes, immature male rats were treated with an antagonist of luteinizing hormone-releasing hormone (LHRH; ORG. 30276) from postnatal days 6-15. Previously, it has been demonstrated that this treatment results in delayed pubertal development, decreased testicular weight, impaired fertility and adult sexual behavior. In the present experiments it was investigated whether the decreased testicular weight was correlated with morphological changes in the testis. Also, by using an artificial insemination technique, the biological activity of spermatozoa of adult male rats, treated during early prepuberty with the LHRH antagonist (LHRH-A), was tested. The present results demonstrated a decrease in the diameter of the testicular tubuli of LHRH-A-treated rats. The number of Sertoli cells per tubular cross-section was also smaller. But qualitatively no differences could be observed in the testis. All stages of maturation of the seminiferous epithelium were equally frequently represented in LHRH-A-treated males compared with controls. Artificial insemination using spermatozoa obtained from the epididymis of LHRH-A-treated rats, resulted in a pregnancy rate of 100%, similar to the control rate. From the present data, we conclude that the infertility in adult male rats, treated with an antagonist to LHRH during prepubertal life, does not result from malfunction in the maturational processes in the germinal cells and the testes as a whole, despite the observation of changes in the testicular morphology. The infertility of LHRH A-treated male rats can be explained by the observed impairment of sexual behavior. We suggest, that a central action of the antagonist of LHRH when administered to immature male rats may lead to permanent changes in the development of sexual behavior. PMID- 2110280 TI - Oxysterol mediated changes in fatty acid distribution and lipid synthesis in cultured bovine aortic smooth muscle cells. AB - We studied the actions of oxysterols on fatty acid distribution and lipid synthesis in cultured bovine aortic smooth muscle cells. Cultures were labeled with [1-14C]arachidonate or [1-14C]oleate. During a 24-hr incubation, 25- or 22R hydroxycholesterol enhanced the incorporation of label into triglycerides, concomitant with a reduction in the labeling of phospholipids. Cholestantriol or 20-hydroxycholesterol had the opposite effects. They caused a higher incorporation of radiolabel into phospholipids and a reduction of labeling of triacylglycerols. Similar changes were seen in cells labeled with [1-14C]acetate. Therefore, we conclude that oxysterols can promote changes in the distribution of fatty acids between neutral lipids and phospholipids through mechanisms that still need to be clarified. PMID- 2110281 TI - Bone marrow transplantation in lysosomal storage diseases: a prelude to gene insertion therapy. AB - Allogeneic bone marrow transplantation is a therapeutic option for enzyme replacement in children with lysosomal storage diseases, for which no current conventional treatments are curative. Although marrow allografting is costly, intensive, and not risk free, strides are being made in the management and prevention of procedure-related complications. PMID- 2110282 TI - Thrombolytic therapy for myocardial infarction. AB - Thrombolytic therapy has provided a practical means of reducing infarct size and infarct-related mortality. Clinicians must weigh the apparent risks and benefits of thrombolytic therapy: if the ischemic region is large, if treatment can be applied early enough to salvage ischemic myocardium, and if there is no obvious risk of life-threatening hemorrhage, it is likely the patient will benefit from thrombolytic therapy. PMID- 2110283 TI - Dose perturbations at interfaces in photon beams: secondary electron transport. AB - An improved, quantitative version of the partial fluence model [Med. Phys. 14, 585 (1987)] for the calculation of dose perturbations at media interfaces in photon beams is presented and compared with measurements made at interfaces between polystyrene and materials ranging in atomic number from aluminum to lead, for photon beams ranging in energy from 60Co to 24 MV. PMID- 2110284 TI - The calculation of transmission through a photon beam attenuator using sector integration. AB - A calculational scheme is presented for the prediction of the transmitted fraction (TR) through an attenuator of known material and physical dimensions, at any point in a photon beam, for a beam of any shape or size. The method considers the total TR to be composed of scatter and primary components and computes the scatter component by sector integration. The input for the calculations consists of measured narrow- and broad-beam transmitted fractions through lead in air for various circular fields, thicknesses of the attenuator, and angles from the central axis, in a geometry approximating typical treatment conditions. The method has been tested for the case of a uniform half slab and a 45 degree wedge in a 4-MV photon beam. It was found that the use of TR values obtained by the above method reduced the maximum absorbed dose computation error from 8% computed with a commercially available algorithm to 3%, in a typical treatment setup. This method is generally applicable to any shaped attenuator such as a wedge or compensator covering whole or part of a radiation field. PMID- 2110285 TI - Dose distributions in radiosurgery. AB - A PC-based, three-dimensional treatment planning system, which may be used for planning of radiosurgical treatments with the Gamma unit or with any of the radiosurgical techniques based on isocentric linear accelerators (linacs), is described and used to calculate isodose distributions for various linac-based radiosurgical techniques ranging from the single plane rotation to a 4-pi geometry. The latter gives an isotropic dose falloff outside the target volume but cannot be used for practical radiosurgery, while the single plane rotation is simple to use but gives unacceptably shallow dose falloffs in the transverse plane. Dose falloffs for several other techniques of varying degrees of complexity are shown and discussed. Also discussed is the effect of beam energy and beam profiles on radiosurgical dose distributions. PMID- 2110286 TI - Protein-energy malnutrition in AIDS. PMID- 2110287 TI - Refeeding and subsequent growth in the child with AIDS. PMID- 2110288 TI - Outcomes of cancer and noncancer patients on HPN. PMID- 2110289 TI - Nutritional support in an AIDS patient. PMID- 2110290 TI - Brain injury and nutrition. AB - This review has discussed the current status of metabolic alterations and demands, nutrient administration, and nutritional assessment of the head-injured patient. More work is necessary in all areas to further describe and ascertain the nutritional requirements of these patients. Future research in this area should involve specific nutrient requirement, modification of the acute-phase response, and possibly administration of growth factors. PMID- 2110291 TI - Update: measles outbreak--Chicago, 1989. PMID- 2110292 TI - Eosinophilia-myalgia syndrome--Canada. PMID- 2110293 TI - Availability of NIOSH criteria document on hand-arm vibration syndrome. PMID- 2110295 TI - Biotechnology: Wellcome drops TPA. PMID- 2110294 TI - Influence of treatment to sacrifice time and the presence of BrdUrd on chemically induced aberration rates in mouse marrow cells. AB - 4 chemicals, with various modes of clastogenic action were used to evaluate induced chromosomal aberrations in mouse bone marrow at different times after intraperitoneal injection. Aberration frequencies induced by mitomycin C, cyclophosphamide and dimethylbenz[a]anthracene increased with increasing time between treatment and sampling until those time points (approximately 18 h) when significant proportions of second-division metaphases were among the cells being scored; this increase was not obvious following treatment with 4-nitroquinoline 1 oxide. When BrdUrd tablets were implanted prior to treatment and scoring was restricted to first-division metaphases, aberration rates continued to increase for as long as 24 h post-treatment. The presence of BrdUrd did not affect significantly the rate of aberration induction by the chemicals. Our data indicate that the sensitivity of the in vivo mouse marrow assay for clastogenic chemicals can be greatly increased by utilizing BrdUrd to insure the scoring of only first-division metaphases at post-treatment times of approx. 18 h. PMID- 2110296 TI - Selective killing of hepatitis B envelope antigen-specific B cells by class I restricted, exogenous antigen-specific T lymphocytes. AB - Specific B lymphocytes can act as very efficient antigen-presenting cells. They bind antigen with high affinity via their immunoglobulin receptors, process it through the class II major histocompatibility complex (MHC) pathway, and present its fragments to class II-restricted T lymphocytes. In general, exogenous antigens and noninfectious viral particles enter the class II pathway and are selectively associated with class II MHC molecules. The presentation of an exogenous antigen in association with class I molecules has been reported for only a few antigens, including the hepatitis B envelope antigen (HBenvAg). Here we demonstrate that antigen-specific B cells can efficiently deliver HBenvAg to the class I pathway, presenting its fragments to class I-restricted cytotoxic T lymphocytes (CTLs) which kill the specific B cells. This could represent a mechanism of suppression of neutralizing anti-hepatitis B virus (HBV) antibody response, a phenomenon that accompanies the development of the chronic HBV carrier state. PMID- 2110298 TI - Child care: banking on success?. Interview by Jean Gray. PMID- 2110297 TI - Kenneth Clarke: single-mindedness and sincerity. Interview by Norah Casey. PMID- 2110300 TI - Education: P2000 anger. PMID- 2110301 TI - Patient education: chemotherapy and patient information. PMID- 2110299 TI - Daphne Parish: execution dashes hopes. PMID- 2110302 TI - Aggressive treatment and the elderly. PMID- 2110304 TI - Birth of a nursing development unit. PMID- 2110303 TI - A strategy for nursing. Targets for action: enhancing care. PMID- 2110305 TI - The courage to debate. PMID- 2110306 TI - Royal College of Nursing Congress 1990. Quest for quality. PMID- 2110307 TI - Romania appeal: can you help? PMID- 2110309 TI - Best possible taste?. Interview by Charlotte Alderman. PMID- 2110308 TI - Clinical nurse specialists: the specialist debate. PMID- 2110310 TI - Supervision: a cross-cultural approach. PMID- 2110311 TI - Diplomas for the new decade. PMID- 2110312 TI - Management of incontinence: the concept of cost-effectiveness. PMID- 2110313 TI - Design and daily living. PMID- 2110314 TI - Never mind quality. PMID- 2110315 TI - Lampada. PMID- 2110317 TI - Debate decisions. PMID- 2110316 TI - Keeping an eye on care. PMID- 2110318 TI - Safeguarding standards: quality care. PMID- 2110319 TI - Meeting the challenge of racism. PMID- 2110320 TI - Tradimus: the magazine for all nursing students. PMID- 2110321 TI - Equality and opportunity. Interview by Kim Bennett. PMID- 2110322 TI - Project 2000: all change. Interview by Brian Dolan. PMID- 2110323 TI - Role playing. PMID- 2110324 TI - Bill of Rights: Clause nine. PMID- 2110325 TI - Neuroradiological examination of thoracic radiculomyelopathy due to ossification of the ligamentum flavum. AB - Sixteen cases of thoracic radiculomyelopathy due to ossification of the ligamentum flavum (OLF) were analyzed. The patients ranged in age from 39 to 78 years (average 57 years). There were 13 men and 3 women. A significant predilection of OLF for the lower thoracic spine (T9/10, T10/11, T11/12) was noticed. Plain X-ray of the thoracic spine and multidirectional tomography could give important information about the site of ossification. Computed tomography with the intrathecal injection of the water-soluble contrast material clearly demonstrated the ossification and the degree of compression of the spinal cord. The disadvantages of using computed tomography for diagnosing OLF included the necessity for the scan level to be previously decided by other methods because computed tomography of the entire spine was impractical. Magnetic resonance imaging was performed in 14 patients and gave important information about OLF and the compression of the spinal cord. The combination of MRI and computed tomography seems the most useful for the precise diagnosis of OLF. PMID- 2110326 TI - The effects of excitotoxic lesions of the basal forebrain on the acquisition, retention and serial reversal of visual discriminations in marmosets. AB - The effects of N-methyl-D-aspartate-induced lesions of the basal forebrain (which included the cholinergic cells of the nucleus basalis of Meynert) were studied on three aspects of visual discrimination; learning, retention and reversal performance, in the marmoset. Neurobiological investigations revealed that the lesion produced large reductions in choline acetyltransferase activity within anterior regions of cortex, particularly prefrontal. In Experiment 1 lesioned animals showed impaired retention, one week after surgery, of a visual discrimination learned immediately prior to surgery and subsequently showed impaired performance over a series of reversals. The reversal deficit could be characterized as a tendency to perseverate on the previously correct stimulus on the first reversal and as a failure to show serial reversal learning on subsequent reversals. Acquisition of a novel discrimination was not impaired five weeks after surgery. As time of testing may have been a confounding factor, in Experiment 2 the effects of the same lesion on new learning were examined immediately following surgery and the effects on retention a month later. The lesion was found to disrupt new learning but did not affect retention. From the two experiments it is clear that, whereas disruption of retention and new learning was relatively transient, the impairments in reversal performance were more long lasting. In addition, lesioned animals exhibited behavioural hyperactivity and elevations in consummatory and schedule-controlled licking. The disinhibitory and preservative effects observed following lesions of the basal forebrain in this study are similar to those following lesions of the orbitofrontal cortex while the disruption of serial reversal learning is commonly seen following damage to the amygdala. Therefore, these results are consistent with the hypothesis that the range of behavioural effects of the lesion result from damage to the cholinergic afferents to orbitofrontal cortex and to the amygdala, two structures intimately connected to one another. PMID- 2110327 TI - Belladonna alkaloids. PMID- 2110328 TI - Isolated pulmonary blast injury in rats--a new model using extracorporeal shock wave lithotriptor. PMID- 2110329 TI - The contemporary crisis in military medicine. PMID- 2110330 TI - Blood typing errors on U.S. Army identification (ID) cards and tags. PMID- 2110331 TI - Undiagnosed dyslexia in physicians. PMID- 2110332 TI - How to train war surgery specialists: Part II. AB - Since 1950 the peacetime practice of civilian and military surgery has been characterized by increasing specialization and subspecialization. The surgical management of war wounds continues to require a solid foundation in general surgery training and experience, plus additional specific training in war surgery. Even the trauma specialist will face significant differences and difficulties treating war wounds in field hospitals. Neither military nor civilian surgical programs provide this training. This two-part essay identifies major characteristics of war surgery and explores the essential training and education required to prepare civilian and military surgeons for the practice of war surgery. PMID- 2110333 TI - Parental self-assessment and behavioral problems of preschool children. AB - Parents of preschool children undergoing psychiatric evaluation were included in the evaluation process through a parents' group, and their attitudes regarding child-rearing behaviors were measured on five factors. Comparisons of parental attitudes on the five factors, demographic variables, and diagnoses of their children revealed several significant findings, including differences between mothers' and fathers' perceptions of their parenting ability between caucasian and non-caucasian parents as well as differences based on the child's diagnosis. PMID- 2110334 TI - Flugtag-88 (Ramstein Air Show Disaster): an Army response to a MASCAL. AB - A successful response to a mass casualty event must include trained personnel, adequate facilities, and abundant supplies. The medical staff must strictly adhere to triage and classification standards. Landstuhl Army Regional Medical Center (LARMC) triaged, within 30 minutes, 120 casualties from the Ramstein Air Show Disaster--14 patients were admitted, 86 were stabilized and transferred to German facilities, 16 were treated and released, and 4 were expectant. There were 6 subsequent transfers to LARMC. Seven patients were operated upon that day, 7 patients were eventually transferred to Brooke Army Burn Unit, and 3 patients underwent subsequent delayed reconstructive surgery. PMID- 2110335 TI - Malabsorption of thyroxine, calcium, and vitamin D in a thyroparathyroidectomized woman: efficacy of therapy with medium-chain triglyceride oil. AB - A 28-year-old woman with surgically induced hypothyroidism and hypoparathyroidism required large doses of replacement medications due to malabsorption from short bowel syndrome. Malabsorption of thyroxine was documented using the technique of double isotope radioiodothyronine turnover studies. Therapy with medium-chain triglyceride oil improved her malabsorption and favorably influenced the absorption of her medications. PMID- 2110336 TI - Effects of nerve agent antidote and heat exposure on soldier performance in the BDU and MOPP-IV ensembles. AB - This study assessed the effects of nerve agent antidote (atropine/2-PAM chloride versus saline placebo) and heat-humidity (95 degrees F/60% RH versus 70 degrees F/30% RH) on repeated performance of militarily relevant psychological tasks while wearing the battle dress uniform (BDU) and while wearing chemical protective clothing (MOPP-IV). All BDU heat sessions (6 hours) were completed, but with some task impairments and a few subjective reactions. MOPP-IV heat sessions could not be continued beyond 2 hours; all tasks were impaired and subjective reactions were numerous and severe. Atropine/2-PAM significantly shortened endurance time for heat sessions in MOPP-IV. PMID- 2110337 TI - Toe temperatures during arctic training. AB - The surface toe temperature of 10 subjects was monitored in the field in Arctic Norway (minimum air temperature -27 degrees C). The lowest skin temperature recorded was 1.9 degrees C. The mean estimated time for the toe temperature to cool from 25 degrees C to 5 degrees C was 109 minutes (SD, 10.2) at an ambient temperature of -21 degrees C. One subject experienced a toe temperature below 5 degrees C for 2.9 hours during a 27-hour period. Surprisingly none of the subjects demonstrated clinical signs of cold injury, but this does not mean that this exposure was without risk. Cold sensitization could have occurred. PMID- 2110338 TI - Dose-dependent atropine-induced changes in spontaneous electroencephalogram in human volunteers. AB - Atropine is an anticholinergic drug used in military medicine as an antidote following exposure to cholinesterase-inhibiting nerve agents. However, atropine causes neuropsychologic effects that impair performance. In the present study, we examined electrophysiologic indices that may accompany performance deficits. Quantitative electroencephalographic (EEG) analyses of changes induced by atropine (1.5, 3.0, and 6.0 mg/70 kg, intramuscularly) were assessed in seven male volunteers in a placebo-controlled, double-blind, cross-over experiment. Spontaneous EEG recordings were obtained from relaxed subjects before, 2 hours after, and 8 hours after atropine. Atropine significantly increased delta power, decreased alpha power, and tended to increase theta power and reduce beta and theta frequency. EEG indices of vigilance were reduced by the drug. Dose-related increases in sedation and dysphoria were obtained; some subjects liked these effects. Together, these findings confirmed that atropine causes dose- and time related electrophysiologic and subjective effects that predict impaired performance. PMID- 2110339 TI - Acute exertional rhabdomyolysis in hypothyroidism: the result of a reversible defect in glycogenolysis? AB - A 28-year-old man on thyroid hormone replacement following treatment with radioactive iodine for Graves' disease developed an episode of acute exertional rhabdomyolysis. He was found to be hypothyroid and had no rise in serum lactic acid following an ischemic exercise test. With additional thyroid replacement, his ischemic exercise test normalized and his muscle symptoms resolved. This observation suggests that rhabdomyolysis in hypothyroidism may be due to a reversible defect in glycogenolysis and that hypothyroidism should be excluded in patients with rhabdomyolysis and/or myoglobinuria. PMID- 2110340 TI - Suicide prevention at a United States Navy training command. AB - In a 2-year retrospective study, suicide prevention efforts produced a significant reduction in suicide attempts at a U.S. Navy training command. Evidence was presented that suicide prevention may be a more pressing issue at training commands than operational commands. The approach described here focused on instructors rather than on the students who were the usual patients presenting with suicidal ideation or attempts. Instructors were taught how to identify and help individuals at risk and how to get help for them. PMID- 2110341 TI - The prisoner of war. AB - The prisoner of war (POW) experience is greatly influenced by the environmental and sociocultural factors of the particular captivity setting. Among the most important coping mechanisms are communication, maintenance of military social structure, and personality flexibility. Following repatriation some former POWs develop psychiatric disorders, most commonly 1) medico-psychiatric disorders due to illness, physical trauma, or nutritional deficit, 2) post-traumatic stress disorder, 3) adjustment disorder, 4) depression, 5) anxiety disorders, 6) substance use disorders, and 7) family problems. The severity of captivity and the presence or absence of social supports during and after the POW experience play major roles in the recovery or illness that may occur after repatriation. PMID- 2110342 TI - Development of the U.S. Army Ambulatory Care Data Base. AB - In providing more than 22 million outpatient visits per year, the U.S. Army Medical Department is one of the largest Health Maintenance Organizations in the world. Accordingly, the need for an Ambulatory Care Data Base (ACDB) to provide management, epidemiological, and cost indicators has long been recognized by the Army. As part of a multi-year study, the ACDB was developed to meet this need. Issues and problems faced in implementing such a wide-scale effort are discussed. Preliminary results from data collected on over 3 million outpatient visits include types of health care providers and clinic specialties, with the corresponding number of visits. PMID- 2110343 TI - Mass casualties on the modern battlefield: problems and proposed solutions. PMID- 2110344 TI - The emergency medicine specialist in combat triage: a new and untapped resource. PMID- 2110345 TI - New housestaff: officers and physicians. PMID- 2110346 TI - Education and training for war surgery. PMID- 2110347 TI - Oximeters on the pulse. PMID- 2110348 TI - Surgical nutrition--new concepts. PMID- 2110349 TI - Getting it right: the making of practice guidelines. PMID- 2110350 TI - Practice guidelines and standards: an overview. AB - Organized medicine, insurance companies, regulators, and the peer review organizations are all interested in practice guidelines. Recently, the U.S. Congress established the Agency for Health Care Policy and Research, which is charged with overseeing the development of practice guidelines. If properly developed, disseminated, and used, practice guidelines should reduce the incidence of inappropriate care and help control costs. Although guidelines have been used by physicians for years, guidelines now being developed should be more comprehensive, specific, exhaustive, and--on the basis of the best scientific evidence of effectiveness and expert opinion--more effectively discriminate between useful and useless care. Practice guidelines can improve the quality of care when used voluntarily by physicians in practice, when used as standards for quality monitoring and assurance programs, and when used as the basis for reimbursement for services. All interested parties should share responsibilities for the research, development, and production of appropriateness criteria, their translation into guidelines and standards, and the dissemination and maintenance of the guidelines, including evaluation, revision, and updating. PMID- 2110351 TI - Integrating practice guidelines with financial incentives. AB - Practice guidelines, in whatever form, hold significant implications for the delivery and the financing of health care. Hence, great care must be taken in developing them. They must be scientifically sound and thus defensible. They must incorporate clinical perspectives and consider patients' preferences. They must cover appropriate as well as inappropriate services. They must foster creation and adoption of a rational payment system. What guidelines, in their best form, can do is enable physicians, faced with an overwhelming array of often conflicting information, to reduce some of the uncertainty they must cope with and to practice the most clinically effective medicine. For physicians to do so requires valid information from a credible source, most often in conjunction with appropriate financial incentives. PMID- 2110352 TI - Development of practice parameters by physician organizations. PMID- 2110353 TI - Medical specialty societies and the development of practice policies. PMID- 2110354 TI - Relationship of clinical indicators and practice guidelines. PMID- 2110355 TI - The development of anesthesia guidelines and standards. AB - Anesthesiology is considered a leading specialty with respect to medical risk management and patient safety. The American Society of Anesthesiologists (ASA) developed its first practice guidelines in 1968 and published its first set of stricter practice standards in 1986. The standards are detailed specifications for the minute-to-minute conduct of anesthesia practice. An impetus for ASA standards development has been the belief that physicians should develop their own standards rather than have them imposed by nonphysician third parties. PMID- 2110356 TI - Developing specialty-wide standards of practice: the experience of ophthalmology. AB - In 1986, the American Academy of Ophthalmology (AAO) developed national guidelines for the diagnosis and treatment of major eye disease. A core committee of 10 AAO members detailed the framework and goals for the guidelines and wrote a series of broad criteria outlining the ophthalmologist's moral and ethical responsibilities. Several panels of AAO-physician experts were formed to develop guidelines for specific conditions. The panels were formed according to subspecialty and were assigned well-defined issues, such as the diagnosis and management of chronic, adult-onset open-angle glaucoma. Process and structure standards were developed first; outcome standards are scheduled for future development. The first five sets of practice guidelines have been approved by the AAO's Governing Council. These include standards for the comprehensive eye exam, as well as four disease-specific guidelines--open-angle glaucoma, glaucoma suspect, diabetic eye disease, and cataract. PMID- 2110357 TI - The advent of clinical standards for professional liability. AB - The development of clinically based written standards to reduce the frequency and severity of medical malpractice loss appears to be gaining in popularity among provider specialty groups and professional liability underwriters. To date, such standards have addressed problems in specialties such as obstetrics and anesthesia where dollar losses associated with malpractice claims have been high. Guidelines can be developed and used by providers on a purely voluntary basis or mandated on an involuntary basis by third parties such as malpractice insurance companies or legislators. Because the advent of risk-control standards is a relatively new phenomenon, formal scientific studies on the long-term benefits of such guidelines have not yet been published. However, it appears that sharp reductions of malpractice losses in specialties such as anesthesia have coincided with the implementation of formal written standards specifically designed for liability control. This has led some liability insurance carriers to decrease premiums associated with specialists following such standards. Many providers are understandably concerned about the potential use of written standards by plaintiff attorneys in medical malpractice suits. Although it is possible that such policies and guidelines could be admitted into evidence to show that a provider breached the legal duty or standard of care owed to a patient, it is uncertain whether these risk-control standards could ultimately pass the evidentiary rules of relevancy or materiality in a given lawsuit. It is clear, however, that the consensus-based process of creating clinical standards and guidelines specifically for controlling professional liability losses is itself a powerful and emerging standard for health care risk management programs. PMID- 2110358 TI - Clinical practice guidelines at an HMO: development and implementation in a quality improvement model. AB - Harvard Community Health Plan (HCHP) is adapting to clinical medicine the managerial principles and methods of quality improvement theory that were originally developed and successfully applied in industrial settings. An essential step in applying the quality improvement cycle to clinical medicine is the setting of standards or specifications for clinical care. HCHP has chosen to focus its standard-setting efforts on the development of clinical algorithms, which provide an excellent basis for specifying and communicating optimal care processes and for evaluating actual clinical care. When implemented effectively, clinical algorithms may improve quality and decrease costs by guiding clinicians toward more standardized, high-quality, cost-effective clinical strategies and by facilitating more valid measurement of clinical process and outcomes. This article describes the evolution, structure, methods, and future agenda of the Algorithm Based Clinical Quality Improvement Process (ABCQIP) at HCHP. PMID- 2110359 TI - The Minnesota Clinical Comparison and Assessment Project. AB - Efforts to quantify and improve the effectiveness and efficiency of health care services are critical to the health care system in the United States. Essential components of these efforts are clinician involvement and support and reliable clinical information systems. Organized medicine and the hospital industry in Minnesota have initiated and funded the Minnesota Clinical Comparison and Assessment Project (MCCAP) to begin to document, compare, and improve health care services. Through MCCAP, a forum, comprising leaders in the Minnesota health care community, oversees efforts to collaboratively identify and address quality of care. In addition, MCCAP will adapt guidelines for specific conditions/procedures, collect hospital-level data on clinical practices in the state relative to those conditions/procedures, and provide feedback so that physicians can evaluate their practice and modify it, if necessary, to improve quality of care. PMID- 2110360 TI - Glucuronidation of codeine and morphine in human liver and kidney microsomes: effect of inhibitors. AB - Glucuronidation of codeine was detected and compared with that of morphine in microsomes from human livers and kidneys. Vmax values for codeine-6-glucuronide (C6G) were 0.54 +/- 0.24 and 0.74 +/- 0.35 nmol/mg/min. in the livers and 0.10 and 0.13 nmol/mg/min. in the kidney, respectively, when codeine and UDP glucuronic acid (UDPGA) were incubated with microsomal preparation. The corresponding Km values were 2.21 +/- 0.68 and 1.41 +/- 0.36 mM in the livers and 6.69 and 4.12 mM in the kidney. The average codeine glucuronyltransferase (GT) activity was 14-fold lower in the six kidneys than in the 11 livers. Higher GT activities were observed in liver microsomes from patients who had been exposed to enzyme inducers. Rates of glucuronide formation from morphine correlated significantly with those from codeine in both human liver and kidney microsomes. Morphine, amitriptyline, diazepam, probenecid and chloramphenicol inhibited codeine glucuronidation with Ki values of 3.6, 0.13, 0.18, 1.7 and 0.27 mM, respectively. PMID- 2110361 TI - Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases. AB - Cellular transformation by oncogenic retroviruses encoding protein tyrosine kinases coincides with the tyrosine-specific phosphorylation of multiple protein substrates. Previous studies have shown that tyrosine phosphorylation of a protein of 120 kDa, p120, correlated with src transformation in chicken embryo fibroblasts. Additionally, we previously identified two phosphotyrosine containing cellular proteins, p130 and p110, that formed stable complexes with activated variants of pp60src, the src-encoded tyrosine kinase. To study transformation-relevant tyrosine kinase substrates, we have generated monoclonal antibodies to individual tyrosine phosphoproteins, including p130, p120, p110, and five additional phosphoproteins (p210, p125, p118, p85, and p185/p64). These antibodies detected several of the same tyrosine phosphoproteins in chicken embryo fibroblasts transformed by avian retroviruses Y73 and CT10, encoding the yes and crk oncogenes, respectively. Protein substrates in mouse, rat, hamster, and human cells overexpressing activated variants of chicken pp60src were also detected by several of the monoclonal antibodies. PMID- 2110363 TI - Low density lipoprotein receptor-binding activity in human tissues: quantitative importance of hepatic receptors and evidence for regulation of their expression in vivo. AB - The heparin-sensitive binding of 125I-labeled low-density lipoprotein (LDL) to homogenates from 18 different normal human tissues and some solid tumors was determined. The binding to adrenal and liver homogenates fulfilled criteria established for the binding of LDL to its receptor--namely, (i) saturability, (ii) sensitivity to proteolytic destruction, (iii) inhibition by EDTA, and (iv) heat sensitivity. When the binding of 125I-labeled LDL was assayed at a constant concentration (50 micrograms/ml), the adrenal gland and the ovary had the highest binding of normal tissues. The highest binding per g of tissue overall was obtained in homogenates of a gastric carcinoma and a parotid adenoma. When the weights of the parenchymatous organs were considered, the major amount of LDL receptors was contained in the liver. To study the possible regulation of hepatic LDL-receptor expression, 11 patients were pretreated with cholestyramine (8 g twice a day for 3 weeks). Increased binding activity (+105%, P less than 0.001) was obtained in homogenates from liver biopsies from the cholestyramine-treated patients as compared with 12 untreated controls. It is concluded that the liver is the most important organ for LDL catabolism in humans and that the receptor activity in this organ can be regulated upon pharmacologic intervention. Further studies are needed to confirm the possibility that certain solid tumors can exhibit high numbers of LDL receptors. PMID- 2110362 TI - Induction of interleukin 1 and tumor necrosis factor by mycobacterial proteins: the monocyte western blot. AB - Infection with Mycobacterium tuberculosis involves mononuclear phagocytic cells as hosts to intracellular parasites, accessory cells in the induction of the immune response, effector cells for mycobacterial killing, and targets of cytotoxic lymphocytes. When stimulated by whole mycobacteria or various mycobacterial preparations, monocytes and macrophages produce the cytokines interleukin 1 and tumor necrosis factor, which possess multiple functions, including immune induction, and may be responsible for the fever and cachexia prominent in tuberculosis. To identify mycobacterial proteins that may directly activate production of these cytokines, culture filtrate of M. tuberculosis that had been subjected to gel electrophoresis and transferred to nitrocellulose paper was used to stimulate monocyte production of cytokines. Fractions representing molecular weights of 46,000 and 20,000 consistently induced both interleukin 1 and tumor necrosis factor. The magnitude of the monocyte responses to these fractions was similar to that to intact mycobacteria or optimal concentrations of lipopolysaccharide. This stimulatory effect was not due to contamination with either bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as it was abolished by digestion with Streptomyces griseus protease but was unaffected by ammonium sulfate precipitation, preincubation with polymyxin B, or depletion of lipoarabinomannan by immunoaffinity chromatography. Proteins identified by this system may have considerable potential as immunogens, as the capacity to directly stimulate mononuclear phagocyte production of cytokines is an essential property of adjuvants. PMID- 2110364 TI - Lipoprotein lipaseBethesda: a single amino acid substitution (Ala-176----Thr) leads to abnormal heparin binding and loss of enzymic activity. AB - The molecular defect that leads to a deficiency of lipoprotein lipase (LPL) activity in the proband from a Bethesda kindred has been identified. The pre- and post-heparin plasma LPL mass in the proband was elevated when compared to controls; however, there was no detectable LPL activity, indicating the presence of a defective enzyme (termed LPLBethesda). Analysis of the patient's post heparin plasma by heparin-Sepharose affinity chromatography demonstrated that the mutant LPL had an altered affinity for heparin. Southern blot hybridization of the gene for LPLBethesda revealed no major rearrangements. Northern blot analysis of LPLBethesda mRNA from patient monocyte-derived macrophages revealed normal sized mRNAs (3.4 and 3.7 kilobases) as well as normal cellular mRNA levels when compared to control macrophages. Sequence analysis of polymerase chain reaction amplified LPL cDNA revealed a G----A substitution at position 781 of the normal LPL gene that resulted in the substitution of an alanine for a threonine at residue 176 and the loss of an SfaNI site present in the normal LPL gene. Amplification of cDNA by the PCR followed by digestion with SfaNI established that the patient was a true homozygote for the mutation. Expression of LPL cDNA in COS-7 cells resulted in the synthesis of a nonfunctional LPL enzyme establishing that the Ala----Thr substitution was the mutation responsible for the inactive LPL. The identification of this mutation in the LPL gene defines a region of the LPL enzyme, at Ala-176, that is essential for normal heparin binding and catalytic activity. We propose that an amino acid substitution in this critical region of LPLBethesda results in the synthesis of a nonfunctional enzyme that leads to the chylomicronemia syndrome expressed in this proband. PMID- 2110365 TI - Distribution of saposin proteins (sphingolipid activator proteins) in lysosomal storage and other diseases. AB - Saposins (A, B, C, and D) are small glycoproteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Concentrations of these saposins in brain, liver, and spleen from normal humans as well as patients with lysosomal storage disease were determined. A quantitative HPLC method was used for saposin A, C, and D and a stimulation assay was used for saposin B. In normal tissues, saposin D was the most abundant of the four saposins. Massive accumulations of saposins, especially saposin A (about 80-fold increase over normal), were found in brain of patients with Tay-Sachs disease or infantile Sandhoff disease. In spleen of adult patients with Gaucher disease, saposin A and D accumulations (60- and 17-fold, respectively, over normal) were higher than that of saposin C (about 16-fold over normal). Similar massive accumulations of saposins A and D were found in liver of patients with fucosidosis (about 70- and 20-fold, respectively, over normal). Saposin D was the primary saposin stored in the liver of a patient with Niemann-Pick disease (about 30-fold over normal). Moderate increases of saposins B and D were found in a patient with GM1 gangliosidosis. Normal or near normal levels of all saposins were found in patients with Krabbe disease, metachromatic leukodystrophy, Fabry disease, adrenoleukodystrophy, I-cell disease, mucopolysaccharidosis types 2 and 3B, or Jansky-Bielschowsky disease. The implications of the storage of saposins in these diseases are discussed. PMID- 2110367 TI - Identification of an Agrobacterium tumefaciens virulence gene inducer from the pinaceous gymnosperm Pseudotsuga menziesii. AB - Inducible T-strand mobilization from the Ti plasmid of Agrobacterium tumefaciens to the genome of a plant host is mediated by the activation of a cascade of bacterial virulence genes. It is initiated when the bacterium senses the presence of a low molecular weight inducer secreted by the plant. Although many hydroxyphenylpropanoid and phenolic compounds can activate the virulence cascade, the only native inducers that have been identified to date are acetosyringone and hydroxyacetosyringone. A new inducer, the phenylpropanoid glucoside coniferin, has now been isolated from Pseudotsuga menziesii (Douglas-fir). Agrobacterium strains that were more tumorigenic on gymnosperms were more effectively induced by coniferin. PMID- 2110366 TI - Amino acid residues that affect interaction of tissue-type plasminogen activator with plasminogen activator inhibitor 1. AB - Fibrinolysis is regulated in part by the interaction between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1, a serine protease inhibitor of the serpin family). It is known from our earlier work that deletion of a loop of amino acids (residues 296-302) from the serine protease domain of t-PA suppresses the interaction between the two proteins without altering the reactivity of t-PA towards its substrate, plasminogen. To define more precisely the role of individual residues within this loop, we have used site-directed mutagenesis to replace Lys-296, Arg-298, and Arg-299 with negatively charged glutamic residues. Replacement of all three positively charged amino acids generates a variant of t-PA that associates inefficiently with PAI-1 and is highly resistant to inhibition by the serpin. Two t-PAs with point mutations (Arg-298----Glu and Arg-299----Glu) are partially resistant to inhibition by PAI-1 and associate with the serpin at intermediate rates. Other point mutations (Lys-296----Glu, His-297----Glu, and Pro-301----Gly) do not detectably affect the interaction of t-PA with PAI-1. None of these substitutions has a significant effect on the rate of catalysis by t-PA or on the affinity of the enzyme for its substrate, plasminogen. On the basis of these results, we propose a model in which positively charged residues located in a surface loop near the active site of t-PA form ionic bonds with complementary negatively charged residues C-terminal to the reactive center of PAI-1. PMID- 2110368 TI - Isolation and characterization of fra-2, an additional member of the fos gene family. AB - Antiserum raised against a Fos peptide (amino acids Lys-127 to Arg-140 of chicken c-Fos) recognizes a 46-kDa Fos-related protein in cell lysates of growth stimulated chicken embryo fibroblasts. Induction of the 46-kDa protein is transient but is slightly prolonged relative to c-Fos following growth stimulation. Using a mixed oligonucleotide probe encoding the peptide antigen, we have cloned the chicken genomic locus that encodes this protein and have determined its gene structure. This locus consists of four exons, each of which has some homology with the corresponding exons of the chicken c-fos gene, and it expresses a 6-kilobase mRNA after growth stimulation. The deduced amino acid sequence of the gene (323 amino acids) contains a "leucine zipper" and includes five distinct regions that exhibit strong sequence homology to the recently identified fos-related antigens Fra-1 (rat) and FosB (mouse) as well as c-Fos. Since the other regions of the gene have little homology to any of these three proteins, this gene was named "fra-2." When the fra-2 gene was overexpressed by an avian retrovirus vector, it caused transformation of chicken embryo fibroblasts. The fra-2 gene product formed a complex in cells with the c-Jun protein, indicating that c-fos and fra-2 share biological and biochemical functions. PMID- 2110369 TI - Cholinergic mechanisms in the rat's hypothalamus mediate the stimulatory effect of thyrotropin-releasing hormone on gastric secretion. AB - To assess the possible involvement of cholinergic mechanisms in the hypothalamic nuclei in the stimulatory effect of TRH on gastric secretion, rats were infused with thyrotropin-releasing hormone (TRH), cholinergic agonist or antagonist, and normal saline through previously implanted hypothalamic cannulae. Administration of TRH or pilocarpine into the lateral cerebral ventricle or the anterior hypothalamus caused a dose-related increase in gastric volume and acidity in rats. On the other hand, administration of either atropine or D-tubocurarine into the same brain sites caused the opposite effects. Furthermore, the stimulatory effect of TRH or pilocarpine on gastric secretion was completely abolished by pretreatment of the CSF or the anterior hypothalamus with atropine and to a lower degree, D-tubocurarine. Administration of TRH, pilocarpine, atropine or D tubocurarine into the lateral hypothalamus produced only a slight effect on gastric volume and acidity. However, the gastric volume or acidity was not affected by administration of either TRH, pilocarpine, atropine or D-tubocurarine into the ventromedial hypothalamus in our rats. The data indicate that the cholinergic muscarinic receptor mechanisms in the anterior hypothalamus may mediate the stimulatory effect of TRH on gastric secretion in rats. PMID- 2110370 TI - Effects of demethylchlortetracycline phototoxicity on the structure and functions of rat liver mitochondria. AB - The phototoxic effects of demethylchlortetracycline (DMCT) with UVA radiation on isolated rat liver mitochondria were studied. DMCT at concentration of 21.5 microM with 5.53 x 10(-2) J cm-3 of UVA was found to be a potent uncoupler of oxidative phosphorylation. DMCT alone also uncoupled mitochondria but at higher concentrations (105 microM). ATPase activity was remarkably induced in mitochondria exposed to DMCT (21.5 microM) plus UVA (120% of DNP-stimulated ATPase activity). Content of ATP in such mitochondria when measured after addition of ADP was much smaller than that in control mitochondria. Ultrastructurally, mitochondria treated either with DMCT (21.5 microM) or with UVA alone stayed in the condensed configuration. On the other hand, uncoupled mitochondria treated with DMCT plus UVA became swollen and were changed into the orthodox configuration. PMID- 2110371 TI - Neurophysiological and biochemical changes evoked by valproic acid in the central nervous system. AB - (1) Valproic acid is an anticonvulsant agent widely used in the management of various forms of epilepsy, including absence, myoclonic and tonic-clonic seizures. (2) It also has anticonvulsant potency in a wide variety of animal models of epilepsy. (3) This action is generally thought to be exerted through modulation of the activity of the endogenous inhibitory neurotransmitter, gamma aminobutyric acid. (4) Evidence that valproic acid interacts with the gamma aminobutyric acid system is presented. (5) Interactions of valproic acid with other neurotransmitters, i.e. aspartate, glutamate, taurine, serotonin, as well as with cyclic nucleotides and hormones are also considered. (6) Direct effects of valproic acid on excitable membranes and its relationships with analgesia are outlined. PMID- 2110372 TI - [Neurological mutants of Drosophila melanogaster]. PMID- 2110373 TI - [Eicosanoids]. PMID- 2110374 TI - [Enzyme immunoassay and nervous tissue-related proteins]. PMID- 2110375 TI - The economics of anxiety. PMID- 2110377 TI - Comparison of subcutaneous and conjunctival routes of Rev 1 vaccination for the prophylaxis of Brucella ovis infection in rams. AB - The serological response and protection conferred against Brucella ovis by the Rev 1 vaccine was evaluated in both adult (experiment 1) and young rams (experiment 2) vaccinated either subcutaneously or conjunctivally. In experiment 1 the Rev 1 vaccine protected 55.5 per cent and 100 per cent, respectively, of subcutaneously and conjunctivally vaccinated rams against three consecutive challenges that infected 100 per cent of unvaccinated controls. In experiment 2, Rev 1 protected 100 per cent of rams vaccinated subcutaneously and 70 per cent of those vaccinated conjunctivally against a challenge dose able to infect all the unvaccinated controls. The serological response after vaccination was significantly lower in rams vaccinated conjunctivally than in those vaccinated subcutaneously. PMID- 2110376 TI - Tuberculosis in captive seals: bacteriological studies on an isolate belonging to the Mycobacterium tuberculosis complex. AB - Culture of tuberculous lesions from six of 14 captive seals yielded an organism which, on the basis of biochemical and drug sensitivity tests, was identified as Mycobacterium bovis, although the organism showed a weak cording pattern and was glycerol tolerant. It was pathogenic in rabbits and guinea pigs and after passage the organism exhibited strong cord formation and was glycerol intolerant. Restriction endonuclease analysis and sodium dodecyl-sulphate polyacrylamide gel electrophoresis indicated that the organism belonged to the Mycobacterium tuberculosis complex. Restriction patterns indicated that infection in the six seals was from a single source. Western blotting with monoclonal antibody to M bovis identified antigens at 23 and 27 kDa in M bovis which were absent from the seal isolates. PMID- 2110378 TI - Swainsonine toxicosis suppresses appetite and retards growth in weanling rats. AB - Two groups of weanling rats were treated with swainsonine, the toxin responsible for 'pea-struck' and locoism in grazing animals, for 21 days. The initial dose rate was 46 mg kg-1 d-1 in one group, and 7.6 mg kg-1 d-1 in the other. Food and water intake, urinary volume and bodyweight gain were recorded for each rat and compared with those for pair-fed and ad libitum fed control individuals. At both dose rates, swainsonine caused marked retardation of growth consequent to profound suppression of appetite. In intoxicated rats, intake of water was also diminished. PMID- 2110379 TI - Self-regulating factor present in culture supernatants of regenerating hepatocytes in adult rats. AB - The auto-regulation mechanism of liver regeneration after partial hepatectomy was investigated in rats. Hepatocytes isolated from the individual remnant livers at various times after 70% removal of the liver were cultured, and determination of DNA synthesis of the cultured hepatocytes and collection of culture supernatants were performed. The maximum value of DNA synthesis was observed at 1 day after the operation and then gradually decreased, and the liver weights recovered rapidly during 2-4 days. The culture supernatants harvested from these primary cultured hepatocytes isolated from the rats at 2, 3 and 4 days after the operation suppressed dose-dependently DNA synthesis of hepatocytes which were isolated from normal rats and stimulated by epidermal growth factor (EGF) and insulin in vitro. The supernatants were non-cytotoxic against hepatocytes, and the activity of them was fairly stable for acid and heat treatments but not for proteolytic enzyme. No inhibition of the binding of EGF to the receptors on hepatocytes was observed. Furthermore, the factor showed an inhibitory activity of mitogen-induced DNA synthesis of human peripheral blood lymphocytes in culture. These results suggested that hepatocytes themselves might modulate the process of liver regeneration by secreting a growth inhibitory factor. PMID- 2110380 TI - T-cell recognition of HLA class II molecules induced by gamma-interferon on a colonic adenocarcinoma cell line (HT29). AB - HLA class II molecules may be induced on non-lymphoid cells by gamma-interferon (IFN-gamma). We investigated if HLA class II molecules induced by IFN-gamma on the HT29 colonic carcinoma cell line are functional, i.e. if they may be recognized by allogeneic T cells. We found that IFN-gamma-treated HT29 (HT29IFN) cells could not induce primary proliferative responses of peripheral blood T lymphocytes, nor were they able to induce proliferation in T-lymphocyte clones (TLC) specific for HLA class II molecules found on HT29IFN. However, in the presence of exogenous interleukin 2 (IL-2), 1 of 5 DQw8-specific TLC proliferated when restimulated with HT29IFN, and 3 of these 5 TLC could very effectively inhibit the growth of HT29IFN, probably due to a cytotoxic effect. Both the proliferative response and the cytotoxicity were inhibited by anti-DQ MoAb. We conclude that T cells may recognize HLA-DQ molecules on non-lymphoid cells, which may be of relevance for autoimmune diseases, graft-versus-host disease, and possibly for the recognition of malignant cells. PMID- 2110381 TI - Expression of a zinc finger gene in HTLV-I- and HTLV-II-transformed cells. AB - Gene products encoded by the human T cell leukemia virus (HTLV) types I and II mediate transformation by the transactivation of cellular genes necessary for proliferation, probably including transcriptional regulatory factors. By searching for factors that may control proliferation, a zinc finger gene (225) was identified that was constitutively expressed in all HTLV-I- or HTLV-II transformed cell lines examined, whereas in normal T cells it was only transiently expressed after mitogenic stimulation. The 225 gene was also constitutively expressed in two HTLV-I-transformed helper T cell clones, but not in the parental cell lines. Thus this putative cellular transcriptional factor, which was abnormally expressed in retrovirus-infected cells, may have a role in transformation. PMID- 2110382 TI - In vivo receptor-mediated phosphorylation of a G protein in Dictyostelium. AB - Extracellular adenosine 3',5'-monophosphate (cAMP) serves multiple roles in Dictyostelium development, acting as a chemoattractant, a cell-cell signaling molecule, and an inducer of differentiation. The Dictyostelium G-protein alpha subunit G alpha 2 appears to be the major transducer linking the surface cAMP receptor to these intracellular responses. On stimulation of cells with cAMP, G alpha 2 is phosphorylated on one or more serine residues, resulting in an alteration of its electrophoretic mobility. Phosphorylation of G alpha 2 is triggered by increased occupancy of the surface cAMP receptor and is rapid and transient, coinciding with the time course of activation of physiological responses. PMID- 2110383 TI - Phosphorylation of the polymeric immunoglobulin receptor required for its efficient transcytosis. AB - The endosomal compartment of polarized epithelial cells is a major crossroads for membrane traffic. Proteins entering this compartment from the cell surface are sorted for transport to one of several destinations: recycling to the original cell surface, targeting to lysosomes for degradation, or transcytosis to the opposite surface. The polymeric immunoglobulin receptor (pIgR), which is normally transcytosed from the basolateral to the apical surface, was used as a model to dissect the signals that mediate this sorting event. When exogenous receptor was expressed in Madin-Darby Canine Kidney (MDCK) cells, it was shown that phosphorylation of pIgR at the serine residue at position 664 is required for efficient transcytosis. Replacement of this serine with alanine generated a receptor that is transcytosed only slowly, and appears to be recycled. Conversely, substitution with aspartic acid (which mimics the negative charge of the phosphate group) results in rapid transcytosis. It was concluded that phosphorylation is the signal that directs the pIgR from the endosome into the transcytotic pathway. PMID- 2110384 TI - Protease nexin-II (amyloid beta-protein precursor): a platelet alpha-granule protein. AB - Protease nexin-II (PN-II) [amyloid beta-protein precursor (APP)] and the amyloid beta-protein are major constituents of neuritic plaques and cerebrovascular deposits in individuals with Alzheimer's disease and Down syndrome. Both the brain and the circulation have been implicated as sources of these molecules, although they have not been detected in blood. Human platelets have now been found to contain relatively large amounts of PN-II/APP. Platelet PN-II/APP was localized in platelet alpha-granules and was secreted upon platelet activation. Because PN-II/APP is a potent protease inhibitor and possesses growth factor activity, these results implicate PN-II/APP in wound repair. In certain disease states, alterations in platelet release and processing and clearance of PN-II/APP and its derived fragments could lead to pathological accumulation of these proteins. PMID- 2110385 TI - Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) regimen for adults with advanced sarcoma. AB - The mesna, doxorubicin, ifosfamide, dacarbazine regimen produced a 47% response rate (including 10% complete responses) in 105 eligible adults with advanced sarcoma. The major dose-limiting toxicity was granulocytopenia. There was one toxic death from sepsis. Central nervous system and renal toxicity occurred infrequently, perhaps as a result of the continuous-infusion schedule. This regimen is being evaluated further in advanced disease, the adjuvant setting, and in combination with bone marrow colony-stimulating factors. PMID- 2110387 TI - Role of the bisphosphonate etidronate in the therapy of cancer-related hypercalcemia. AB - Bisphosphonates (formerly diphosphonates), analogues of endogenous pyrophosphates, are potent inhibitors of osteoclastic bone resorption. While the exact mechanism of action remains poorly understood, etidronate, the only bisphosphonate currently available in the United States for the treatment of hypercalcemia, decreases the elevated serum calcium levels and alleviates the symptoms associated with hypercalcemia of malignancy. Both open and controlled clinical studies have demonstrated that this agent, administered at a dose of 7.5 mg/kg/d in 2-hour intravenous infusions over 3 to 7 days, promotes normocalcemia. In a randomized study, etidronate was shown to be superior to maximally approved doses of calcitonin. Moreover, when administered to patients without overt renal failure (serum creatinine less than 2.5 mg/dL), the drug is remarkably free of significant acute toxicity and side effects. Therefore, an important therapeutic aspect of this agent is that it permits concurrent antibiotic and chemotherapy administration. Judicious use of appropriate and specific pharmacologic intervention strategies in the patient with cancer-related hypercalcemia is expected to enhance quality of life, improve systemic cancer therapy tolerance, and reduce the morbidity of this serious neoplastic complication. PMID- 2110386 TI - Ifosfamide and mesna: response and toxicity at standard- and high-dose schedules. AB - In two sequential trials, 154 patients were treated with dosages of ifosfamide, ranging between 8 and 18 g/m2 divided over 4 days, with mesna uroprotection. The first was a phase II efficacy trial in 125 advanced sarcoma patients (Antman et al: J Clin Oncol 7:126-131, 1989), while the second was a dose escalation trial involving 29 patients (Elias et al: J Clin Oncol 8:170-178, 1990). In the first trial, patients received 8 to 10 g/m2 ifosfamide either by bolus or continuous infusion. The response rate for the 64 patients receiving bolus administration was 23% compared with 12% for the 60 patients receiving a continuous infusion schedule (P = .09). Of the 154 patients, 144 had sarcoma and had failed at least one previous regimen. Of these 144, 4% responded completely and 23% had a complete or partial response. The maximum tolerated dose of ifosfamide was 16 g/m2 in the second trial. Dose-limiting renal toxicity was observed at 18 g/m2 ifosfamide (Elias et al: J Clin Oncol 8:170-178, 1990). The duration of myelosuppression and the frequency and severity of mucositis and renal tubular acidosis were dose-dependent. A median of 11 days (range, 8 to 18) of granulocytopenia (less than 500/microL) were observed. Thus, autologous bone marrow reinfusion was not required. Severe central nervous system toxicity (transient confusion, hallucinations, and somnolence) was observed sporadically at both low- and high-dose levels. The first four patients on the standard-dose study did not receive mesna because it was unavailable; three developed gross hematuria. In patients who received mesna, hematuria was uncommon. Hematuria in the group as a whole was significantly associated with a lack of uroprotection, but was not associated with prior cyclophosphamide, pelvic radiotherapy, age, or bolus versus a continuous infusion schedule. Patients receiving ifosfamide with mesna uroprotection can tolerate considerable dose escalation over the usual prescribed doses before nonhematologic toxicity becomes dose-limiting. Ifosfamide, with its broad activity in solid tumors, may prove to be an important addition to high-dose combination-chemotherapy regimens (Elias et al: J Clin Oncol 8:170-178, 1990). PMID- 2110388 TI - Use of selected visceral protein measurements in the comparison of branched-chain amino acids with standard amino acids in parenteral nutrition support of injured patients. AB - Twenty injured patients in the intensive care unit were randomized to receive parenteral nutrition with either 21% (STD) or 46% (HBC) branched-chain amino acids to compare the response of nitrogen balance (NB), somatomedin-C/insulin like growth factor I (SMC), circulating fibronectin (FBN), and prealbumin (PA). NB was measured and serum collected for SMC, FBN, and PA on days 1, 4, 7, 14, and 21 of nutritional intervention. The treatment groups did not differ significantly for age, weight, injury severity score, trauma score, Apache II score, acute phase protein concentrations, or type of injury. Comparison of baseline measurements revealed no significant differences in SMC, FBN, or PA. Both groups received similar doses of nonprotein energy and nitrogen. Baseline urea nitrogen excretion was slightly higher in the STD group (216 +/- 55 vs 268 +/- 54 mg/kg/day p = 0.049). Although NB was significantly improved over baseline during subsequent study days, there were no differences between groups after the day-1 measurement. SMC increased significantly from baseline on day 4 in the STD group, on day 7 in the HBC group, and on days 14 and 21 in both groups. There was no significant difference in SMC concentrations between groups on any day. Each group demonstrated a significant increase in PA from baseline on days 7, 14, and 21; however, no difference was seen when groups were compared. FBN increased significantly from baseline on day 14 in the HBC group and on days 7 and 14 in the STD group. FBN measurements were significantly different between groups on day 14 (STD, 179 +/- 71 vs HBC, 229 +/- 59 micrograms/ml; p less than 0.05). NB, PA, SMC, and FBN improve significantly during parenteral nutrition of traumatized patients. With the measured variables, there appears to be no significant difference between STD or HBC amino acids when used as part of parenteral nutrition in injured patients. PMID- 2110389 TI - [Experience in using new drug preparations for treating adult patients with acute intestinal infections]. AB - Ciprofloxacin (Bayer, FRG), a derivative of hydroxyquinolone acid, was used for the treatment of patients with shigellosis and salmonellosis and for the sanitation of Salmonella carriers. The drug turned out to exert a positive effect on bacteriological sanitation of the body. In order to treat patients with food toxinfection of unknown etiology, use was made of intetrix (Farmacos, Socialist Federal Republic of Yugoslavia). Inclusion of the drug into combined treatment of patients with food toxinfections did not show any material advantages. PMID- 2110390 TI - This and that: an unsuitable eponym, leeches, and the transmutation of the disciplines. PMID- 2110391 TI - [Possibilities of chemical detoxification of aflatoxin]. AB - The efficacy of inactivation of aflatoxin B1 (AFB1, 2.0-2.6 mg per kg) in aqueous medium in exposure to 21 chemicals or their mixtures for two hours and for two days was evaluated by measuring the extracts on a fluorescence spectrophotometer. Reduction to less than 10% of the original AFB1 content within two hours was recorded when the medium contained 1.5% potassium permanganate, 2.5 and 5% Chloramin B (Lachema) or soda, and when there was 5% ammonia heated to 60 degrees C, 5% sodium hydroxide, potassium hydroxide or calcium hydroxide, or 50% chromosulphuric acid. AFB1 and other fluorescing metabolites were completely destroyed after two days of exposure to a 5% ammonia solution heated to 60 degrees C for the first two hours and after two days of exposure to 5% Chloramin B, 5% soda, 5% calcium hydroxide, 50% chromosulphuric acid, and mixture of 2.5% sulphuric acid with 0.75% potassium permanganage. Acids used alone had the lowest effectiveness. PMID- 2110392 TI - Evaluation of three midazolam-xylazine mixtures. Preliminary trials in dogs. AB - The depressant effects of midazolam and xylazine on the central nervous system (CNS) were evaluated in 12 dogs. Xylazine was administered to six dogs (1.1 mg/kg intravenously [IV]) followed in 5 minutes by midazolam (1.0 mg/kg intramuscularly [IM]). In a second group of six dogs, xylazine (2.2 mg/kg IM) was followed in 5 minutes by midazolam (1.0 mg/kg IV). Both drug regimens induced rapid and profound sedation or anesthesia. Duration of action varied with the doses and routes of administration. Dogs given the high dose of xylazine IM had an arousal time of 95.4 +/- 8.9 minutes and a walking time of 155.4 +/- 8.8 minutes. These values exceeded the IV xylazine values threefold. Partial reversal of CNS depression was accomplished with either a benzodiazepine antagonist (flumazenil) or an alpha-2 antagonist (yohimbine). In a separate trial, a mixture of xylazine (0.55 mg/kg), midazolam (1.0 mg/kg), and butorphanol (0.1 mg/kg) with and without glycopyrrolate was evaluated in eight dogs. As with the xylazine-midazolam combinations, the CNS depressant effect of this mixture was clinically indistinguishable from anesthesia achieved with other rapid-acting injectable agents. Clinical signs of CNS depression were readily and completely antagonized by the simultaneous injection of flumazenil and yohimbine. PMID- 2110393 TI - WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty first report. PMID- 2110394 TI - Glucosinolates toxicity in growing rats: interactions with the hepatic detoxification system. AB - 1. Glucosinolate-rich diet (RM) in growing rats increased liver (a), kidneys (b), and thyroid (c) weights and depleted feed intake (d), growth curve (e) and T4 and T3 plasma levels (f). 2. Oral administration of phenobarbital enhanced the toxic effect of RM on (b), (d) and (e) and did not modify the toxic effect of RM on (a), (c) and (f). 3. RM had a depleting effect on hepatic microsomal P-450 specific activity. 4. RM had an enhancing effect on hepatic glutathione S transferase and UDP-glucuronyltransferase specific activities. 5. These results indicate that some glucosinolate derivatives released by gut microflora metabolism are further metabolized by the hepatic detoxification system, and that they could play the role of co-toxic or co-detoxic molecules. PMID- 2110395 TI - Vitamin E status in Sudanese children with protein-energy malnutrition. AB - Total tocopherols and alpha-tocopherols were estimated in the plasma of children with severe malnutrition (14 marasmus; 11 marasmic kwashiorkor; five kwashiorkor) and related to the total plasma lipids and different plasma lipid classes. If the mere plasma concentrations were taken as an index of the vitamin E status, five children with marasmus, five children with marasmic kwashiorkor, and two children with kwashiorkor would have been regarded as deficient (less than 500 micrograms/dl). However, if total tocopherols and alpha-tocopherols were related to the total plasma lipids, all malnourished children--except one--showed values within the limits found in healthy American children. The study shows that low tocopherol/lipid ratios are not a constant feature in severely malnourished children. PMID- 2110396 TI - [The virological supervision of drinking water quality--a review]. AB - Drinking-water must be free of pathogenic organisms; this challenge refers to pathogenic viruses too. In order to control virological aspects of water quality realistic and practicable monitoring procedures, esp. practical microbial assays, must be performed. They should include in all cases standard plate counts and counts of total or faecal coliform bacteria. Counts of coliphages in combination with standard plate counts and counts of coliform bacteria offer a practical and reliable indicator system for evaluating the virological safety of treated drinking-water supplies in the case of drinking-water reclaimed from contaminated raw water, esp. surface water. PMID- 2110397 TI - Indirect immunoperoxidase and immunofluorescence staining of Bordetella bronchiseptica in formalin-fixed, paraffin-embedded lung tissues of rabbits. AB - Indirect immunoperoxidase (IP) and immunofluorescence (IF) techniques were developed, and used for the identification of B. bronchiseptica in formalin fixed, paraffin-embedded lung tissues of 26 rabbits displaying focal chronic interstitial pneumonia, vascular changes, and chronic bronchitis and bronchiolitis. Labelled B. bronchiseptica organisms were observed at the level of the bronchial and bronchiolar mucosa, both in areas affected by chronic bronchitis-bronchiolitis and in zones that were free of lesions. B. bronchiseptica was not observed in areas of focal chronic interstitial pneumonia, nor in vessels exhibiting inflammatory changes. B. bronchiseptica was observed also in a few rabbits that were culturally negative for this agent. The results obtained suggest that B. bronchiseptica could have been related to the lesions of chronic bronchitis and bronchiolitis observed, but not to the changes of focal chronic interstitial pneumonia and vasculitis, as areas affected by these alterations did not exhibit B. bronchiseptica immunoreactivity. PMID- 2110398 TI - Regulation of prostaglandin biosynthesis with flunixin meglumine in the bovine species. AB - Flunixin meglumine (FM) was injected in 2 oophorectomized cows to follow changes in basal levels of the main circulating prostaglandin (PG)F2 alpha metabolite, 15 ketodihydro-PGF2 alpha. A rapid decrease in the levels was seen after FM and the effect was lasting for about 6 h. Thus, to obtain a full effect of the drug on prostaglandin synthesis it is recommended that FM should be injected 4 times daily. This concept was further studied in 3 cycling heifers which obtained FM 4 times daily from day 15 of the estrous cycle for 7 days (totally 28 injections). During the period of drug administration, prostaglandin metabolite levels were decreased and the expected pulsatile release seen during luteolysis was delayed. The pulsatile release started about one day after cessation of treatment and then luteolysis occurred. Progesterone levels were normal during the FM treatment and dropped concomitantly with the pulsatile release of PGF2 alpha. The levels of progesterone decreased to low levels before the heifers showed signs of estrus and ovulated. The administration of FM causes a situation resembling that seen during early pregnancy and FM can be a useful tool in understanding the mechanism behind maternal recognition of pregnancy. PMID- 2110399 TI - The effect of Toxoplasma gondii infection in flunixin meglumine treated pregnant ewes as monitored by plasma levels of 15-ketodihydroprostaglandin F2 alpha, progesterone, oestrone sulphate and ultrasound scanning. AB - The aim of this study was to examine the endocrinological response (15 ketodihydro-PGF2 alpha, progesterone and oestrone sulphate) of pregnant ewes which were constantly treated with flunixin meglumine (FM) after infection with Toxoplasma gondii. Seven Swedish Peltsheep ewes were dosed orally with 2,000 T. gondii oocysts at 90.5 (82-94) days of pregnancy. The ewes were treated with FM, 1 mg/kg, intramuscularly twice a day, starting one day before infection until the end of the gestation period. Further three ewes were treated with FM alone during the corresponding time of pregnancy. Another four ewes were used as uninfected and untreated controls. All infected ewes developed antibodies to T. gondii and aborted, but the FM treated control group and the non-treated control group, which remained seronegative, delivered the lambs in the normal gestation range. No early abortions (less than 10 days after infection) were seen in the infected group. The endocrinological changes reflected the pathological changes in the uterus and foetuses. FM could neither completely inhibit prostaglandin release during abortion nor the physiological change of the hormone before parturition even though it depressed prostaglandin release before abortion or parturition and eliminated fever. The infectious process caused by the organism was probably not affected. FM treatment alone had no observed negative effects on pregnant ewes and their foetuses. PMID- 2110400 TI - [The effect of glucocorticoid on the glucose metabolism of pigmy goats. 1. Selected metabolites of energy metabolism]. AB - In order to study mechanisms in ruminants responsible for glucocorticoid-induced hyperglycemia the effects of a single intravenous dose of a glucocorticoid on energy metabolism were investigated by measuring plasma levels of glucose, lactate, free fatty acids (FFA), 3-hydroxybutyrate (3-HOB) and acetoacetate (AcAc). Experiments were performed on four castrated male African pygmy goats at two metabolic states: "fed" with a single daily meal of hey and "fasted" with starvation for 3 days. The untreated goats served as their own control. The glucocorticoid application to fed animals resulted in an increase in glucose level (+43%) lasting more than 11 h and an irregular increase of lactate. The concentration of 3-HOB was increased especially before feeding (+64%). In contrast, FFA were decreased (-27%) the second day after glucocorticoid application. In fasted goats the glucocorticoid also caused an increase in glucose level (+25%). The effect was smaller than in fed animals. Concentrations of FFA, 3-HOB and AcAc were 10, 20 and 35% lower than those of untreated goats. With regard to the antiketotic use of glucocorticoids the decrease of plasma levels of FFA and ketone bodies in starving animals is of special importance. Obviously the animals were able to use glucose again as a main energy source instead of FFA. PMID- 2110401 TI - Androgens in fetal pigs in relation to sex of neighbour(s). AB - Concentrations of androgens in blood and/or fetal fluids were determined in pig fetuses 35, 56/58 and 115 days of age. For each fetus the sex of its neighbour(s) in utero was determined. Irrespective of the sex of neighbour(s), no significant differences in testosterone levels were found between the different groups of females, or between the different groups of males. When females and males were compared, significant differences were found. At a fetal age of 35 days testosterone concentrations (mean and SD) in amniotic fluid were 0.17 +/- 0.06 and 0.26 +/- 0.05 nmol/l in females and males, respectively (p less than 0.01). At a fetal age of 56/58 days, the corresponding values were 0.14 +/- 0.04 and 0.21 +/- 0.07 nmol/l (p less than 0.01). At this age testosterone concentrations in mixed umbilical blood plasma were 0.22 +/- 0.08 in females and 1.12 +/- 0.64 nmol/l in males (p less than 0.001). At term the mean concentrations of testosterone were 2.4 and 2.5 nmol/l in mixed umbilical blood plasma and 1.6 and 1.7 nmol/l in fetal fluid in females and males, respectively. The levels of dehydroepiandrosterone in fetal fluid at this stage were 1.6 nmol/l in females and 1.7 nmol/l in males. Concentrations of dihydrotestosterone were below the sensitivity level of the method (less than 0.09 nmol/l) in all samples tested. It is concluded that male neighbours do not influence the androgen levels in blood plasma and fetal fluids of the females. PMID- 2110402 TI - Influence of exogenous estradiol on the concentration of antitrypsin, albumin, N acetyl-beta-D-glucosaminidase and somatic cells in milk of cows at various lactation stages. AB - Estradiol benzoate (0.02 mg/kg of body weight) was injected (i.m.) daily to 13 ovariectomized cows in their first or third lactations during early (60-90 days), mid (140-200 days) and late (240-300 days) lactation. The majority of the udder quarters were free of bacteria throughout the experiment. Signs of clinical mastitis were observed after 9-19 days of treatment in cows at mid and late lactation. This was accompanied by a decrease in milk yield, an increase in milk somatic cell count (MSCC) and increases in milk concentration of antitrypsin and serum albumin (as indicator of increased permeability); and milk NAGase activity (as indicator of epithelial cell damage or release of the enzyme from phagocytes). NAGase activity was first to increase and on some occasions was not accompanied by an increased MSCC. The response was either absent (first lactation) or relatively mild (third lactation) in cows at the early stages of lactation. The intensity of the inflammatory response increased with advancing lactation stage. Generally, the response of cows in the third lactation was greater than that of cows in the first lactation at a corresponding stage of lactation. Three cows which received the control treatment with vehicle alone showed no changes in any of the parameters except a slight decrease in antitrypsin. All inflammatory indicators correlated negatively with quarter milk production; milk NAGase activity was superior in this respect (r = -0.75). All correlation coefficients were generally higher after, rather than before the hormone treatment. PMID- 2110403 TI - Milk temperature in the claw piece of the milking machine and mammary surface temperature are predictors of internal mammary temperature in goats. AB - Mammary internal and surface temperatures and milk temperature were correlated using five lactating goats. Internal mammary temperature was estimated using temperature-sensitive transmitters placed deep within the parenchyma of each mammary half. External mammary temperature was estimated using infrared thermography of four mammary skin sites: T1, teat end; T2, teat base; G1, about 20 mm above the teat base; and G2, about 20 mm ventral to the base of the gland deep to the thigh. The thermistor bead used for estimating milk temperature was placed in the claw piece where the short milk tube of the liner attaches. This placement minimized cooling effects of milk contact surfaces. The overall correlations of milk temperature with mammary temperatures ranged from 0.45 to 0.64. Correlations among the six paired values for the four external sites ranged from 0.76 to 0.92. Milk and surface temperatures, milking time, and milk weight were employed in various combinations as covariables; these were calculated within animal, within half. Milk temperature was the single most important predictor of internal mammary temperature in all models. Milk temperature alone or combined with covariables can be used to predict internal mammary temperature. PMID- 2110404 TI - Clinical signs and performance of pigs treated with different doses of carbadox, cyadox and olaquindox. AB - An experiment was designed to study the clinical effects of different levels of carbadox, cyadox and olaquindox in the ration on health, weekly weight gain and feed conversion in pigs. Four different carbadox and olaquindox (25, 50, 100 and 200 ppm) levels and five different cyadox (25, 50, 100, 200 and 400 ppm) levels were tested in groups of 6 pigs during 6 weeks. The 13 groups were compared with a control group fed on the same diet with only vehicle. After one week the first clinical sign, a high faecal dry matter (FDM) content, was observed in the 200 ppm carbadox group, followed by the 100 and 50 ppm carbadox, the 400 and 100 ppm cyadox, and the 200 and 100 ppm olaquindox groups two weeks later. A second clinical sign, urine drinking from the floor or from pen-mates, was observed in the same pens, occurring in the same sequence. The third important clinical sign, a decreased abdominal volume, was also observed in almost the same sequence, however, in the 50 ppm olaquindox and cyadox groups this clinical sign was not observed. Average weekly weight gain was significantly decreased in the higher carbadox and olaquindox groups. Weight gain was significantly increased in the 200 ppm cyadox group. Hematocrit values were significantly increased in the 200 and 100 ppm carbadox groups only. From this study one may conclude that, within the dosages used, carbadox is more harmful than olaquindox for pigs, and it seems that cyadox is harmless for pigs in dosages up to 400 ppm. PMID- 2110405 TI - Fertility of mares after postovulatory insemination. AB - In a first experiment, 11 Finnhorse mares were examined every six hours during late oestrus by rectal palpation and ultrasonography to determine the time of ovulation. The mares were inseminated over one to three subsequent cycles, 6-12 (n = 5), 12-18 (n = 5), 18-24 (n = 5) and 24-30 (n = 5) hours after ovulation. Pregnancies were terminated by prostaglandin injection 21 days after insemination. All mares inseminated within 18 hours of ovulation conceived but no mare inseminated 24 hours or more after ovulation conceived. In a second experiment, 14 mares were examined every day at about the same time and inseminated after ovulation had been detected, within 0-27 hours of ovulation. Pregnancies were terminated by prostaglandin injection 25 days after insemination and the animals inseminated again. Forty-six per cent of the mares (13 out of 28) were pregnant 16 days after insemination but there was early embryonic death in five mares, i.e. only 29% of the mares became and remained pregnant. The equine ovum seems to be capable of being fertilized for at least 18 hours after ovulation. However, the high incidence of early embryonic death in the second experiment suggests that the viability of the embryo may have decreased. PMID- 2110406 TI - Coagulation profile of dairy cattle in the periparturient period. AB - A coagulation profile including prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT) and fibrinogen concentration was determined in 52 clinically healthy German Black Pied cattle during the periparturient period. In these cows a hypercoagulability appeared within the first 48 hours after parturition. Prothrombin time and partial thromboplastin time for these animals were significantly shorter than those of nonpregnant animals. In addition, a hypercoagulability could be observed during the last three days before parturition. In comparison to cows whose calves were removed through the birth canal with assistance, animals on which a cesarean section was performed displayed a distinctly shorter partial thromboplastin time immediately after parturition and also a significantly lower fibrinogen concentration 3 as well as 24 hours after parturition. PMID- 2110407 TI - [A new technic of intraoperative radiotherapy: the Lyon intraoperative device]. AB - Since November 1985, we performed Intra Operative Radiation Therapy in 53 cases, essentially in gastric cancer (20 patients) and in pancreatic cancer (22 patients). Mortality and morbidity were not increased by the use of Intra Operative Radiation Therapy. Our follow up is too short to get any valid conclusions about IORT in gastric cancer. However, for unresectable pancreatic cancer, we observed an improvement of the survey when patients were treated by "Surgery, IORT and External post operative radiotherapy". We also studied the relief of abdominal and back pain of unresectable pancreatic cancer: in our experience, the survey was longer and more confortable for patients treated with surgery and IORT. In conclusion it appears that today IORT is surely a good palliative treatment for unresectable pancreatic cancer, and longer experience is needed to conclude for resectable pancreatic cancer and for gastric cancer. PMID- 2110408 TI - Effects of a gonadotropin-releasing hormone agonist on progesterone formation in cultured human granulosa cells. AB - Human granulosa cells from follicles of natural cycles (13 women) in mid- or late follicular phase were cultured in modified Medium-199. Human luteinizing hormone (100 micrograms/l), follicle-stimulating hormone (100 micrograms/l) and gonadotropin-releasing hormone agonist (GnRHa) (10(-12) to 10(-6) mol/l) alone or in combination were added to the culture medium. Medium content of progesterone was analysed. In granulosa cells obtained in the mid-follicular phase, the basal progesterone formation averaged 0.5 pg.cell-1.(48 h)-1. FSH caused a 3-fold stimulation. GnRHa (10(-6) mol/l) had a variable influence on the basal progesterone formation, whereas it consistently inhibited (40-50%) the FSH response. In granulosa cells from late follicular phase basal progesterone formation averaged 5 pg.cell-1.(48 h)-1 and was stimulated 3- to 6-fold by LH. GnRHa (10(-6) mol/l) stimulated the basal progesterone formation and caused a tended to potentiate the LH response on progesterone formation. It is concluded that GnRHa at relatively high concentrations exerts direct effects on gonadotropin-stimulated progesterone formation of human granulosa cells and that these effects are different (inhibitory or stimulatory) dependent on the degree of follicular maturation, and/or type of gonadotropin used. PMID- 2110409 TI - Paradoxical growth hormone response to thyrotropin-releasing hormone in acromegaly. Clinical correlations and prognostic value. AB - We have investigated the effect of TRH on the release of GH in 20 acromegalic patients (14 females and 6 males) before and after selective removal of a pituitary tumour via transsphenoidal route. The follow-up period was 8 years. Pre operatively the paradoxical response was present in 15 patients (75%). Mean GH values in TRH responders were significantly lower than in non-responders. According to the size and expansion diffusion of the adenoma, the patients were divided into 3 classes. The percentage of paradoxical response in patients in class III was significantly lower than in the other two classes. Postoperatively, mean GH values in pre-operative TRH responders were significantly lower than in non-responders; among 15 responders, 13 (86%) had postoperative GH levels under 5 micrograms/l; among 5 non-responders only 2 (40%) had GH values under 5 micrograms/l. Postoperatively 8 patients still had GH responsiveness to TRH: 6 with GH levels persistently (follow-up 8 years) under 5 micrograms/l and 2 with elevated GH values. The other 7 patients, who were responders pre-operatively and non-responders postoperatively, persistently exhibited low GH levels, except one subject who showed an increase in GH levels with reappearance of the paradoxical response, two years after surgery. These results suggest: 1. the paradoxical response may be expressed only when the hypothalamus-pituitary interactions are intact; 2. the disappearance of the paradoxical response cannot surely suggest a remission, and 3. the presence of a pre-operative paradoxical response is a good prognostic feature. PMID- 2110410 TI - Prompt recovery of plasma arginine vasopressin in diabetic coma after intravenous infusion of a small dose of insulin and a large amount of fluid. AB - We studied the changes in plasma arginine vasopressin in 5 patients with diabetic ketoacidosis and one patient with non-ketotic hyperosmolar coma who had marked hyperglycemia (36.6 +/- 4.6 mmol/l, mean +/- SEM) and dehydration. Plasma osmolality (Posm) was 342.2 +/- 11.4 mOsm/kg H2O, and hematocrit, serum protein, and blood urea nitrogen were also elevated at hospitalization. Circulating blood volume was decreased by approximately 21% as compared with that on day 7. Plasma AVP level was increased to 8.5 +/- 1.6 pmol/l at hospitalization. When hyperglycemia was improved by iv infusion of a small dose of insulin plus fluid administration, plasma AVP level promptly decreased to 2.4 +/- 0.4 pmol/l within six hours. When plasma AVP level had normalized, Posm was still as high as 305 mOsm/kg H2O, but the loss of circulating blood volume was only 4.2% of the control state. Plasma AVP level was positively correlated with change in hematocrit (plasma AVP = 3.58 + 0.45.hematocrit, r = 0.468, p less than 0.01), serum protein (r = 0.487, p less than 0.01), Posm (r = 0.388, p less than 0.01), and blood glucose (r = 0.582, p less than 0.01). Plasma AVP level was negatively correlated with the change in circulating blood volume (plasma AVP = 3.6 - 0.14.change in circulating blood volume, r = -0.469, p less than 0.01). These results indicate that both non-osmotic and osmotic stimuli are involved in the mechanism for AVP release in patients with diabetic coma, and that the non osmotic control of AVP may contribute to circulating homeostasis, protecting against severe blood volume depletion in diabetic patients suffering from hyperglycemia and dehydration. PMID- 2110411 TI - Thyrotropin releasing hormone does not stimulate prolactin release in the preterm human fetus. AB - Previous studies have suggested that fetal PRL secretion does not respond to stimuli such as TRH, metoclopramide, and cimetidine. It was postulated that the lack of response to TRH could be due to the possibility that, in the term fetus, lactotropes secrete PRL maximally and would be unresponsive to further stimulation. In order to study this hypothesis, 200 micrograms TRH or saline were administered to preterm pregnant women in labor. Maternal blood was obtained before TRH and saline administration. Maternal and cord blood were obtained at parturition. PRL, TSH, T4 and T3 concentrations were measured in all sera. TRH administration induced a significant increase in maternal serum PRL, TSH and T3 concentrations. In the cord blood of newborns whose mothers received TRH, serum TSH, T4 and T3 concentrations were significantly higher than in cord blood of newborns whose mothers received saline. Cord blood serum PRL concentrations were unchanged after TRH administration. This latter finding suggests that fetal lactotropes do not respond to TRH in the preterm fetus. Desensitization of fetal PRL secreting cells to TRH stimulation and/or the inhibitory effect of elevated fetal circulating corticosteroids on TRH-induced PRL secretion may explain the absent PRL response to TRH during fetal life. PMID- 2110412 TI - Growth hormone in type I diabetic and healthy man. AB - Conflicting data are found in the literature concerning the growth hormone response to growth hormone-releasing hormone and the insulin-like growth factor I level in Type I diabetes mellitus. The GH response to GHRH and the serum IGF-I level were studied in 29 moderately to well regulated male diabetic patients and 20 age-matched controls. The mean fasting glucose and HbA1c (normal less than 6.5%) levels were, respectively: 10.2 +/- 0.8 mmol/l and 7.1 +/- 0.2%, and 4.1 +/ 0.1 mmol/l and 5.4 +/- 0.1% (mean +/- SEM). The GH response to GHRH was higher in the diabetic patients at 15, 30 and 45 min (p less than 0.05), and also delta peak GH was higher compared with controls: 34.8 +/- 5.6 vs 18.0 +/- 2.4 micrograms/l (p less than 0.02). The serum IGF-I level was lower in the diabetic patients: 460 +/- 30 vs 700 +/- 60 U/l (p less than 0.01). No correlations could be demonstrated between delta peak GH, serum IGF-I or HbA1c level. When only patients with a mean fasting glucose less than or equal to 7.0 mmol/l and normal HbA1c (5.8 +/- 0.3%) were analysed, delta peak GH was also elevated compared with controls: 47.0 +/- 16.3 vs 18.0 +/- 2.4 micrograms/l (p less than 0.02). No difference was observed in GH response or serum IGF-I level in 5 patients with (pre)proliferative retinopathy compared with patients without this complication. It is concluded that in Type I diabetes the GH response to GHRH is increased, even in well regulated patients, and that the serum IGF-I level is depressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110413 TI - Impact of nutrition status on morbidity and mortality in a select population of geriatric rehabilitation patients. AB - To determine whether the level of protein-calorie undernutrition at presentation correlated with the subsequent risk of developing in-hospital complications independently of nonnutrition factors influencing outcomes, a prospective study was conducted of 110 consecutive admissions to a Geriatric Rehabilitation Unit (GRU) of a Veteran's Administration hospital. In total, 54 variables were evaluated as possible predictors of outcomes. The risk of developing at least one complication while on the GRU was studied by using multivariate techniques (discriminant function analysis) and was found to correlate with, in order of significance, functional status as admission, serum albumin concentration at admission, amount of weight lost in the year before admission, and the presence or absence of a renal or pulmonary disease. Nutrition variables also independently correlated with the risk of developing an infectious complication or a major life-threatening complication and dying within the hospital. These data indicate the importance of nutrition status in geriatric rehabilitation patients. PMID- 2110414 TI - Relative efficiency of a commercial lactase tablet. PMID- 2110415 TI - Unusual mucopolysaccharide disorder with corneal and scleral involvement. AB - A 68-year-old man and a 66-year-old woman had diffuse corneal stromal deposits that stained with alcian blue and colloidal iron but did not react with periodic acid-Schiff stain and lipid stains. Similar deposits were found within postmortem sclera in one case, but not in other ocular or extraocular tissues. The abnormal material was sensitive to testicular hyaluronidase and chondroitinase. The material reacted with monoclonal antibody 9-A-2 after digestion by chondroitinase AC in one case and ABC in both cases, which is consistent with the identification of the glycosaminoglycans chondroitin 4-sulfate and dermatan sulfate. Electron microscopic examination of the cornea in both cases disclosed granular material in vacuoles dispersed extracellularly and, rarely, in keratocytes. Results of blood and skin fibroblast enzyme assays for clinically relevant mucopolysaccharidoses and mucolipidoses were normal in both patients, and there were no somatic abnormalities suggesting a storage disease. PMID- 2110416 TI - Low-dose intraocular tissue plasminogen activator for treatment of postvitrectomy fibrin formation. PMID- 2110417 TI - Lipid and apolipoprotein levels in six Solomon Island societies differ from those in a U.S. white population. AB - Levels of plasma cholesterol, triglycerides, and apolipoproteins (apo) AI, AII, and E in 560 males and 744 females from six Solomon Island societies were compared with levels in age- and sex-matched participants in the Rochester Family Heart Study (RFHS). The overall average cholesterol, triglyceride, apo AI, and apo AII levels for all the Solomon Island societies were significantly lower than levels for the RFHS (P less than 0.001). The mean level of apo E for these societies was significantly higher than levels in RFHS in spite of the fact that the levels of triglycerides were significantly lower. Normally, apo E is a major constituent of triglyceride-rich very-low-density lipoprotein (VLDL). For both sexes, none of the Solomon Island societies showed a significant correlation of plasma cholesterol levels with apo E. In the RFHS, this correlation was 0.50 in males and 0.43 in females. Mean apo E levels are estimated to be 4.15-6.0% of the high-density lipoprotein (HDL) protein in the different Solomon Island societies. This study establishes a distinctive Solomon Island lipid profile characterized by the high apo E levels, which appear to be associated primarily with the HDL particle, whereas, in normal Western populations, it is associated primarily with VLDL, and only small quantities are associated with HDL. PMID- 2110418 TI - Ligand binding and G protein coupling of muscarinic receptors in airway smooth muscle. AB - Ligand binding properties of muscarinic receptors were examined in membranes and isolated cells prepared from bovine trachea. The binding of the muscarinic antagonist [3H]quinuclidinyl benzilate (QNB) to both membranes and isolated cells was saturable, reversible, and of high affinity [dissociation constant (KD) = 100 200 pM]. The binding constants of three selective antagonists, pirenzepine, AF-DX 116, and 4-DAMP, were examined, and the results indicate that the smooth muscle cells contain at least two receptor subtypes. The majority of receptors exhibit binding constants for these selective antagonists similar to those of the M2 subtype. AF-DX 116 binding curves indicated the presence of a small population of receptors with binding constants similar to those reported for the M3-subtype. These findings suggest that the smooth muscle cells may contain both M2- and M3 receptors and are in agreement with evidence of the presence of mRNAs coding for these two subtypes in tracheal extracts (A. Maeda, T. Kubo, M. Mishina, and S. Numa. FEBS Lett. 239: 339-342, 1988). [3H]QNB displacement curves of the muscarinic agonist oxotremorine were best described as a sum of binding to high- and low-affinity sites with KD values of 3.8 nM and 2.2 microM. Guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S) shifted the high-affinity sites to low affinity, suggesting that the high-affinity sites may represent receptors coupled to G proteins. Pertussis toxin catalyzed the ADP ribosylation of a 40- to 41-kDa protein band present in the membranes but had no significant effect on high affinity agonist binding, suggesting that most of the receptors are coupled to G proteins in a toxin-insensitive manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110419 TI - Regulatory effect of cholecystokinin on subsequent insulin binding to pancreatic acini. AB - We investigated the regulatory effect of cholecystokinin (CCK) on subsequent insulin binding to pancreatic acinar cells. Rat isolated acini were preincubated with various concentrations of CCK octapeptide (CCK-8) at 37 degrees C. Acini were then washed, resuspended in the binding buffer, and incubated with 8.3 pM 125I-labeled insulin for 60 min at 37 degrees C. Pretreatment with CCK-8 caused inhibition of subsequent 125I-insulin binding that was time and concentration dependent. Significant inhibition was observed with 3 pM CCK-8. Computer analysis of the competition-inhibition study with a nonlinear least-squares curve-fitting program revealed that CCK-8 pretreatment of acini reduced the receptor affinity of the high-affinity binding site. This inhibitory action of CCK-8 was not due to the alteration in degradation or internalization of the tracer. When acini were pretreated with 100 pM CCK-8 for 120 min at 4 degrees C, a reduction in the receptor affinity of the high-affinity binding site was also observed. In pancreatic membrane prepared from acini preincubated with 100 pM CCK-8 for 120 min at 37 degrees C, displacement of 125I-insulin (83 pM) by unlabeled insulin (24 degrees C, 1 h) revealed that CCK-8 inhibited 125I-insulin binding by altering the receptor affinity of the high-affinity binding site. In acinar preparations the inhibitory effect of CCK-8 on 125I-insulin binding was abolished when acini were preincubated with CCK-8 and CCK receptor antagonist L 374718 at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110420 TI - Role of cell type in net lactate removal by skeletal muscle. AB - Net lactate uptake and subsequent pathways for removal were studied in three rabbit skeletal muscle preparations of distinct fiber type composition, i.e., glycolytic (99.1 +/- 0.2% type IIb fibers), oxidative (97.5 +/- 0.6% type I fibers), and mixed (type I, IIa, and IIb fibers). Single-pass perfusions were carried out for 3 h in the presence of glucose, lactate, and [U-14C]lactate. Lactate levels, initially set at either 1 mM (n = 4/prep) or 2 mM (n = 4/prep), were elevated twice during the perfusion at 60 and 120 min. Net lactate uptake (mumol.100 g-1.min-1) was first observed in the oxidative preparation, 1.4 +/- 0.2, at an arterial lactate concentration of approximately 2.5 mM, whereas net lactate uptake in the glycolytic, 0.7 +/- 0.2, and mixed preparations, 7.0 +/- 0.5, was first observed at 4 mM. Net lactate balance, [14C]lactate removal, and 14CO2 release demonstrated strong linear correlations (r = 0.94-0.98) with arterial lactate concentration. To quantify the fate of [14C]lactate, preparations were perfused at a single elevated lactate concentration (approximately 8 mM) for 2 h. Oxidation was the primary means of disposal in the oxidative and mixed preparations, whereas glyconeogenesis dominated removal in the glycolytic preparation. The arterial lactate concentration at which a given muscle switches from net production to net removal, the rate of removal, and subsequent pathway(s) for disposal are a function of that muscle's fiber type composition. PMID- 2110421 TI - Mechanisms of decrease in cytoplasmic motility of alveolar macrophages during immediate asthmatic response in dogs. AB - To study the cytoplasmic motility (CM) of alveolar macrophages (AM) during immediate asthmatic response, we measured remanent filed strength (RFS) in dogs in vivo after Ascaris suum-antigen (AA) inhalation. Four days after instillation of ferrimagnetic particles (Fe3O4, 3 mg/kg) into the right lower lobe bronchus, RFS was measured at the body surface immediately after magnetization of the Fe3O4 particles by an externally applied magnetic field. RFS decreased with time because of particle rotation (relaxation). Relaxation is thought to be correlated to CM of AM (J. Appl. Physiol. 55: 1196-1202, 1983). AA inhalation increased respiratory resistance (Rrs) in 10 dogs (responders; P less than 0.01), and did not change Rrs in five dogs (nonresponders; P greater than 0.50). The relaxation rate (lambda 0) significantly decreased because of AA inhalation in responders (P less than 0.01), whereas lambda 0 did not change in nonresponders (P greater than 0.50). Intravenous injection of indomethacin or diclofenac sodium (5 mg/kg) 30 min before AA inhalation completely inhibited the decrease in lambda 0 induced by AA inhalation, although both drugs did not inhibit the increase in Rrs (P greater than 0.10). In in vitro experiments, AM (5 x 10(6) cells) cells) harvested by bronchoalveolar lavage showed a significant dose-dependent decrease in lambda 0 with prostaglandins (PG) E1 and E2. However, histamine and platelet-activating factor increased lambda 0 significantly (P less than 0.01), whereas PGD2, PGF2 alpha, PGI2, thromboxane A2, leukotrienes B4, C4, and D4, and AA itself were without effect (P greater than 0.50). Furthermore, PGE2 aerosols mimicked AA induced effects on AM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110422 TI - Effects of serosal hypertonicity on water permeability in toad urinary bladder. AB - We studied in toad urinary bladder the effects of serosal hypertonicity on tissue water permeability, granular cell luminal membrane water permeability, and granular cell luminal membrane particle aggregates and compared them with effects of antidiuretic hormone (ADH). In tissues challenged by a hypertonic (447 mosmol/kgH2O) serosal bath, luminal membrane aggregates were structurally similar to those caused by ADH. The tissue water permeability increase induced by serosal hypertonicity was much less than that caused by a maximally stimulating concentration of ADH on tissue in isotonic serosal baths with approximately the same transmural gradient. The difference is explained not only by a reduced incidence of luminal membrane aggregates but also by an increased resistance to water movement at a postluminal membrane site. Measurements of luminal membrane water permeability showed a close correlation with luminal membrane aggregate frequency, indicating that the calculated permeability of an individual aggregate was a constant. Thus the relation of luminal membrane aggregates to tissue osmotic permeability is modified by serosal hypertonicity. Morphological examination of these tissues suggested that luminal membrane aggregates may be less stable in the absence of hormone. This was evident by the proportionally greater number of structures interpreted as aggregates captured in the process of disassembly ("patches"). Membrane depressions containing intramembrane particles ("craters") were also observed. They corresponded in terms of frequency and size to coated pits as seen in thin sections. PMID- 2110423 TI - Ischemia in normoglycemic and hyperglycemic rats: plasma energy substrates and hormones. AB - Seizures are a documented complication to cerebral ischemia. After 10 min of forebrain ischemia in rats, preischemic hyperglycemia invariably leads to severe, most often fatal epileptic attacks. This outcome is related to the exaggerated lactic acidosis, which has been suggested as a possible contributor to severe membrane changes and widespread edema. To find out if circulating hormones or plasma energy substrates modulate this additive damage caused by the hyperglycemia, plasma concentrations of of corticosterone, epinephrine, norepinephrine, dopamine, glucagon, insulin, glucose, free fatty acids (FFA), 3 hydroxybutyrate, and acetoacetate were measured before and in the early recirculation period after 15 min of forebrain ischemia in the rat. Plasma corticosterone levels did not differ between the normo- and hyperglycemic groups. Although not significantly different from control, the catecholamine levels showed a tendency to be higher in the hyperglycemic groups. Therefore, because catecholamines have been reported to have a protective effect during ischemia the present result cannot explain why hyperglycemia aggravates the ischemic damage. Insulin levels seemed to increase during ischemia but not significantly. Levels quickly returned to normal after 30 min of recirculation. FFA concentrations were reduced after the induction of ischemia and appeared lower in all hyperglycemic groups. The level of one of the ketone bodies, 3-hydroxybutyrate, showed a significant decrease in hyperglycemic ischemia in all groups compared with normoglycemic ischemia. The same tendency was seen for acetoacetate. Results are compatible with a protective role of ketone bodies in ischemia. It is concluded that among the hormones and substrates studied only the ketone body concentrations qualify as a modulator of the exaggerated brain damage after ischemia in hyperglycemic subjects. PMID- 2110424 TI - Cerebral blood flow and substrate utilization in insulin-treated diabetic subjects. AB - We compared regional cerebral blood flow (rCBF) and arteriojugular vein differences of glucose, ketones, glycerol, lactate, pyruvate, and O2 in eight subjects with well-controlled insulin-dependent diabetes mellitus (IDDM) and in six healthy volunteers. Duration of diabetes was 19.4 +/- 2.1 yr. Measurements were performed before and after 120 min of insulin infusion and concomitant Biostator-controlled normoglycemia. Net uptake of ketones was seen in IDDM subjects before but not after insulin. Net uptake of glucose did not differ significantly between groups. During normoglycemia the molar ratio of O2 to glucose uptake was lower in IDDM than in nondiabetic subjects (4.68 vs. 5.50; P less than 0.05; Wilcoxon test). Small but significant release of lactate and pyruvate was seen in IDDM but not in nondiabetic subjects. The rCBF was measured by 11CH3F and position emission tomography. Global mean CBF was higher in IDDM subjects (64.9 +/- 5.9 vs. 49.3 +/- 2.7 ml.100 g-1.min-1, means +/- SE in nondiabetic subjects, P less than 0.05). rCBF was enhanced in many cortical and subcortical areas, whereas it was decreased in the head of the caudate nucleus. Neuropsychological testing did not reveal obvious cognitive dysfunction. The results imply that a larger fraction of glucose is nonoxidatively metabolized in the IDDM subjects and furthermore indicate an abnormal rCBF pattern in these subjects. PMID- 2110425 TI - Induction agents for day-case anaesthesia. A double-blind comparison of propofol and midazolam antagonised by flumazenil. AB - Early postoperative recovery was studied using sedation scoring, measurement of flicker fusion frequency and completion of Trieger test figures in 60 male patients who presented for vasectomy under general anaesthesia as day patients. Anaesthesia was induced in groups 1 and 2 (20 patients each) with mean (SD) doses of 0.16 (0.04) mg/kg or 0.16 (0.03) mg/kg midazolam respectively; group 2 received flumazenil 0.55 (0.19) mg after completion of surgery. The remaining 20 patients (group 3) received propofol 1.50 (0.24) mg/kg. Anaesthesia was maintained with isoflurane vaporized in 33% oxygen and nitrous oxide in all patients. Flumazenil tended to improve tests of recovery after midazolam anaesthesia, but early recovery after propofol anaesthesia was associated with better psychomotor test results and less impairment of mental state as judged by sedation and amnesia scoring. PMID- 2110426 TI - The effect of exhaled alcohol on the performance of the Datex Capnomac. AB - We investigated the response of the Datex Capnomac to alcohol in expired air. The greatest response was seen when the Capnomac was set to monitor halothane. There was an approximately linear correlation with blood alcohol levels. This effect is of sufficient magnitude to introduce inaccuracies in the measured concentration of halothane. PMID- 2110427 TI - Minimum airway pressure weaning. Weaning from mechanical ventilation at 50 breaths/minute by reduction of inflation pressure using a pressure generator. AB - Ten patients, whose lungs were ventilated initially with intermittent positive pressure ventilation at conventional rates after myocardial revascularisation or cardiac valvular surgery, were weaned using a valveless high frequency jet ventilator at a constant rate of 50 breaths/minute. The withdrawal of ventilation was achieved, when clinical criteria permitted, by reduction of the tidal volume preset on the jet ventilator in successive stages; this was effected by stepwise decreases in the jet driving pressure. This new mode of weaning at a constant rate of 50 breaths/minute is associated with minimum peak airway pressures. Synchronisation of the patient's breathing with the valveless ventilator is not required and weaning is tolerated well by the patient. Arterial oxygen tension and saturation were maintained throughout weaning and did not decline after extubation of the trachea. PMID- 2110428 TI - The FEF end-tidal CO2 detector. PMID- 2110429 TI - Diverticular disease of the jejunum and its complications. AB - Jejunal diverticulosis is an uncommon, acquired condition that has been encountered recently in four patients. These cases (two patients with diverticulitis, one patient with chronic abdominal pain, and one patient incidentally discovered at laparotomy for colonic diverticulitis) are reported. Acute complications of jejunal diverticulosis include diverticulitis, bleeding, and intestinal obstruction. Chronic complications include intractable abdominal pain, malabsorption, and intestinal pseudo-obstruction. Up to 15 per cent of patients with jejunal diverticulosis may require small-bowel resection for treatment of these acute or chronic complications. The clinical significance, proper diagnostic evaluation, and treatment of jejunal diverticular disease are reviewed. PMID- 2110430 TI - Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. A new job for an old drug? AB - STUDY OBJECTIVE: To evaluate the usefulness and safety of hydroxychloroquine in patients with decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. DESIGN: Prospective, randomized, placebo, double-blind 6-month trial. PATIENTS: Thirty-eight patients with noninsulin-dependent diabetes resistant to commonly used therapies (oral drugs, insulin, combination of insulin and oral drugs). INTERVENTIONS: Two study groups: one received insulin (n = 22) and the other, glibenclamide (n = 16). In each group, half of the patients were randomly allocated into two subgroups who continued the previous treatment but took either placebo tablets or hydroxychloroquine, 200 mg three times a day. The four subgroups were as follows: insulin and placebo (n = 11); insulin and hydroxychloroquine (n = 11); glibenclamide and placebo (n = 8); and glibenclamide and hydroxychloroquine (n = 8). MEASUREMENTS AND MAIN RESULTS: At 6 months, relevant and statistically significant improvement occurred in the 11 patients who received the insulin and hydroxychloroquine (glucose profile decrease, -11.7 mmol/L; 95% CI, -13.9 to -9.5, P = 0.001; glycated hemoglobin A1c decrease, 3.3%; 95% CI, -3.9 to -2.7, P = 0.001). No significant changes were seen in patients on placebo. The daily insulin dose in patients treated with the combined insulin and hydroxychloroquine therapy had to be reduced an average of 30%. No important side effects were detected. CONCLUSIONS: Combining antidiabetic therapy with hydroxychloroquine in decompensated, treatment-refractory patients with noninsulin-dependent diabetes may help to break the vicious circle of hyperglycemia and lead to better management of the disease. PMID- 2110431 TI - Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. AB - PURPOSE: To determine the prevalence of lupus anticoagulant and anticardiolipin in systemic lupus erythematosus (SLE) and in non-SLE disorders, and to evaluate the clinical significance of these autoantibodies as they relate to thromboembolic events, neuropsychiatric disorders, thrombocytopenia, and fetal loss. DATA IDENTIFICATION: A computer-assisted search of the literature (MEDLINE, 1966 to 1989) and review of the bibliographies of all identified articles. STUDY SELECTION: Series of ten or more subjects were included if the assays used for detecting lupus anticoagulant or anticardiolipin met the specified minimal criteria for validity. DATA EXTRACTION: Series were categorized according to antibody type and underlying disease. A systematic appraisal of patient selection methods, study design, and assay methods was done. RESULTS OF DATA ANALYSIS: An analysis of 29 published series (comprising over 1000 patients with SLE) yielded an average frequency of 34% for the lupus anticoagulant and 44% for anticardiolipin. Antiphospholipid antibodies are also prevalent in patients with various non-SLE disorders. In patients with SLE, a statistically significant association exists between the presence of either antibody and a history of thrombosis, neurologic disorders, or thrombocytopenia. The available data suggest, but do not firmly support, an association between antiphospholipid antibodies and history of fetal loss in women with SLE. Contrary to prevailing opinion, none of these associations have been shown conclusively in patients with non-SLE disorders. CONCLUSIONS: The results of predominantly retrospective series suggest that for certain persons (patients with SLE or closely related disorders) antiphospholipid antibodies may be important risk factors for thrombosis, neurologic disease, thrombocytopenia, and fetal loss. Standardized tests for lupus anticoagulant and anticardiolipin, as well as long-term, prospective clinical studies, are needed to determine the prognostic value of antiphospholipid antibodies. PMID- 2110432 TI - Stimulation of interferon-gamma-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction. AB - PSK, a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor (Fr.) Quel, stimulated tumor necrosis factor-induced cytotoxicity against mouse L-929 fibroblast. PSK also stimulated interferon-gamma-induced differentiation of human myelogenous leukemic U-937 and THP-1 cells. The differentiated cells had higher proportions of cells that expressed NBT-reducing activity and alpha-naphthyl acetate esterase activity. Among four PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) had the most potent stimulating activity. This is the first report regarding direct PSK modulation of cytokine action. PMID- 2110433 TI - Increased plasma prolactin levels in a group of men with breast cancer--a preliminary study. AB - Gonadal and hypophyseal hormones were investigated in 15 males with breast cancer and 15 tumour referents, on average 1 month postoperatively. Plasma prolactin was found to be significantly more often elevated in men with breast cancer compared with referents (p less than 0.005). Another group of men with breast cancer disclosed a tendency for lower S-FSH levels compared with the referents (p less than 0.01). No significant difference was seen between cases and referents regarding S-LH, p-estradiol or p-testosterone. The size of the primary breast tumour was correlated with a higher prolactin level. The findings lend support to a theory implicating prolactin and possibly prolactinomas as a risk factor for the disease in males. PMID- 2110434 TI - Interspecies analysis of the chemopreventive efficacy of dietary alpha difluoromethylornithine. AB - The anticarcinogenic efficacy of the polyamine biosynthesis inhibitor, alpha difluoromethylornithine (DFMO), was assessed in three rodent models of human epithelial cancer. In DMBA-induced female, Sprague-Dawley rats, DMFO treatment (3.2 or 6.4 g/kg diet) for 180 days significantly inhibited mammary carcinogenesis and reduced tumor-related intercurrent mortality compared to untreated controls. In male, C57BL/6x DBA/2F1 mice induced with N-butyl-N(4 hydroxybutyl)nitrosamine (OH-BBN), DFMO treatment (2 or 4 g/kg diet) concurrent with the period of carcinogen administration significantly reduced the incidence and severity of urinary bladder carcinomas. In methylnitrosourea (MNU)-induced male Syrian golden hamsters, DFMO (3.2 g/kg diet) numerically reduced the incidence and size of tracheal carcinoma relative to untreated controls. DFMO mediated toxicity was not evident in any of the animals on study, although a slight reduction in mean body weight gain was evident in rats and mice. PMID- 2110435 TI - Some genetic markers among the Bodos of North Bengal, India. AB - Some genetic markers have been examined among the members of the Bodo tribes, North Bengal, India. Gene frequencies have been estimated and comparison has been done to evaluate differentiation with the common population. The overall intergroup heterogeneity was not significant for Rabha and Mech and also in consideration with the local population. But the Totos showed a difference from the local population and differed slightly from Meches and Rabhas. PMID- 2110436 TI - A note on the frequency distribution of AB0 and rhesus blood groups in four Thai populations of Assam (India) and their position among the Mongoloids of this region. AB - An attempt has been made to give a picture of the distribution of AB0 and Rhesus blood groups in four Thai populations of Assam, India. Intragroup heterogeneity and their position among the Mongoloid populations of this region have also been examined. In all of these groups the frequency of the 0-allele was found to be the most predominant one followed by B- and A-alleles, respectively. A similar trend is observed in some other populations of Asia. The populations under study show statistically similarity with none of the Mongoloid populations of Assam. The incidence of Rhesus-negatives in the populations under study ranges from complete absence to below 2%. PMID- 2110437 TI - Double-blind, dose-range-finding study of fleroxacin (RO 23-6240; AM-833) for treatment of complicated urinary tract infections. AB - In a double-blind randomized trial, we evaluated the efficacy and safety of three oral dosage regimens of fleroxacin, a new fluoroquinolone, once daily in 62 patients for the treatment of complicated urinary tract infections. The regimens compared were 200 mg for 10 days (n = 20), 400 mg for 10 days (n = 21), and 600 mg for 10 days (n = 21). Forty-five patients were evaluable for efficacy. A clinical cure was reached in 78% of the patients. Overall, a favorable bacteriological response (negative culture or reinfection at 4 to 6 weeks) was obtained in 36 of 45 (80%) patients. No significant difference could be found among the three dosage groups. During therapy, one Klebsiella ozaenae strain became resistant and one Pseudomonas aeruginosa strain became less susceptible to fleroxacin. In 13 patients, therapy had to be discontinued due to major adverse events (oliguria [n = 1], psychosis [n = 1], photosensitivity [n = 1], insomnia [n = 1], and nausea [n = 9]). Minor side effects were seen in 13 other patients. Increased dosage correlated significantly (P less than 0.01) with total number of adverse events. PMID- 2110438 TI - In vitro activities of combinations of aztreonam, ciprofloxacin, and ceftazidime against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis. AB - The in vitro activities of two-drug combinations of aztreonam, ciprofloxacin, and ceftazidime were studied in 96 clinical isolates of Pseudomonas aeruginosa and in 20 clinical isolates of Pseudomonas cepacia from cystic fibrosis patients. Some synergy was observed with each combination used against P. aeruginosa, but synergy was rare when the combinations were used against P. cepacia. PMID- 2110439 TI - [A case of unresectable liver metastasis from leiomyosarcoma of the stomach successfully treated by intra hepato-arterial chemotherapy with Infuse-A-Port]. AB - This report describes a 55-year-old man who had a curative operation for leiomyosarcoma of the stomach 6 years ago. Unresectable liver metastases was discovered during the second laparotomy and successfully treated by intra hepato arterial chemotherapy, which included MMC, ADM and Therarubicin with Infuse-A Port. He remains well presently with a decrease in the size of the liver metastases and no metastasis to any other organs upon investigation by an abdominal CT 2 years and 2 months after the second laparotomy. PMID- 2110440 TI - Bulky, benign tumor of the external auditory canal. PMID- 2110441 TI - Serum IgA antibodies against Pseudomonas aeruginosa in cystic fibrosis. AB - Serum IgA antibodies to Pseudomonas aeruginosa cell surface antigens were estimated by ELISA. Titres in patients with and without cystic fibrosis and with no pseudomonal infection were low (less than 105 to less than 261). Titres in patients with cystic fibrosis who were chronically infected with P aeruginosa were very high (1200-163,000), and patients who grew the organism intermittently had intermediate titres. Longitudinal studies suggested increasing tissue invasion or involvement of the lower respiratory tract, or both, with increasing time of infection and identified patients with a good prognosis after the onset of pseudomonal infection. Detection of an increased serum IgA titre can give an earlier indication than measurement of the serum IgG titre of the presence of P aeruginosa in the respiratory tract in a proportion of patients. IgA measurement seems to be better than IgG measurement at predicting the reappearance of P aeruginosa after apparent eradication of early infection. These results suggest that this assay may be a valuable additional indicator of the presence of P aeruginosa at the beginning of infection, and of the reappearance of the organism after treatment in the early stages of infection. PMID- 2110442 TI - Egg and breast milk based nitrogen sources compared. PMID- 2110443 TI - [Stimulation of nonspecific antibacterial resistance of mice to opportunistic gram-negative microorganisms with triterpene glycosides from Holothuroidea]. AB - A total fraction of triterpenic glycosides from Cucumaria japonica named cucumarioside was used as a stimulator of nonspecific resistance to bacterial infections in mice. After intraperitoneal administration to mice subsequently infected with various strains of E. coli and Proteus mirabilis, cucumarioside provided survival of 40 to 90 per cent of the infected animals against 100 per cent in the control group. The protective effect directly depended on the dose of cucumarioside. It was optimal to administer the preparation 3 days before the infection. When the preparation was administered at such periods LD50 for Neisseria meningitidis BT-2 and Salmonella minnesota SF 1111 lowered 5 and 4.3 times, respectively. Therefore, the total fraction of triterpenic glycosides from Far Eastern holothuria had a marked ability to increase natural resistance of the animals to infections caused by various gram-negative organisms. PMID- 2110444 TI - [Bacteriocholia and cholic acid level in the bile in cholelithiasis]. AB - Infection of the biliferous system in patients with cholelithiasis was shown to be the most frequent when the levels of cholic acid in bile were low. Physiological concentrations of cholic and deoxycholic acids have antimicrobial activity against organisms not adapted to the presence in bile. Outer drainage of the bile ducts was accompanied by an increase in the levels of cholic acid when at the background of outer decompression bacteria were eliminated from the biliferous system. In vitro studies revealed a synergistic antibacterial effect of cholic and deoxycholic acid combinations with cefazolin. PMID- 2110446 TI - Rhizocticin A, an antifungal phosphono-oligopeptide of Bacillus subtilis ATCC 6633: biological properties. AB - Rhizocticin A, the main component of the antifungal, hydrophilic phosphono oligopeptides of Bacillus subtilis ATCC 6633, was used for sensitivity testing and experiments into the molecular mechanism of the antibiotic action. Budding and filamentous fungi as well as the cultivated nematode Caenorhabditis elegans were found to be sensitive, whereas bacteria and the protozoon Paramecium caudatum were insensitive. Rhizoctonia solani was inhibited in agar dilution tests but not in diffusion tests. The antifungal effect of rhizocticin A was neutralized by a variety of amino acids and oligopeptides. Oligopeptide influence was mainly understood as transport antagonism, and it was concluded that the antibiotic enters the recipient cell via the peptide transport system. L- and D cystine were also identified as potent, general antagonists of the oligopeptide transport. The rhizocticin-antagonism of four other amino acids was taken as a clue to the site of action. Provided that rhizocticin A is split by peptidases of the target cell into inactive L-arginine and toxic L-2-amino-5-phosphono-3-cis pentenoic acid (L-APPA), the latter may interfere with the threonine or threonine related metabolism. PMID- 2110445 TI - Complete nucleotide sequences of seven eubacterial genes coding for the elongation factor Tu: functional, structural and phylogenetic evaluations. AB - The nucleotide sequences of cloned genes coding for the elongation factor Tu of seven eubacteria have been determined. These genes were from Anacystis nidulans, Bacillus subtilis, Bacteroides fragilis, "Deinonema" spec., Pseudomonas cepacia, Shewanella putrefaciens and Streptococcus oralis. The primary structures of the genes were compared to the available sequences of prokaryotic elongation factors Tu and eukaryotic elongation factors 1 alpha. A conservation profile was determined for homologous amino acid residues. Sites of known or putative functions are usually located at highly conserved positions or within highly conserved sequence stretches. The aligned 24 amino acid sequences were used as basis for a phylogenetic analysis. The phylogenetic tree corroborates the kingdom as well as phylum concept deduced from 16S rRNA data. PMID- 2110447 TI - The effect of tissue plasminogen activator on retinal bleeding. AB - Tissue plasminogen activator is a potent thrombolytic agent that recently has been used to treat postvitrectomy fibrin formation. However, a recent report noted anterior and posterior segment bleeding following intracameral tissue plasminogen activator injection. In this study, we performed lensectomy and vitrectomy in 20 rabbits. A retinal blood vessel was incised to stimulate intraocular hemorrhage; bleeding was controlled and vitreous hemorrhage aspirated. Postoperatively, one eye received a 0.1-mL injection of tissue plasminogen activator (25 micrograms); the other received balanced salt solution. The eyes receiving tissue plasminogen activator had a 28% incidence of increased anterior chamber blood and a 61% incidence of increased intravitreal blood. There was no evidence of postinjection bleeding in eyes receiving balanced salt solution. Most cases of bleeding occurred within 24 hours of tissue plasminogen activator injection. Administration of tissue plasminogen activator in the setting of segmented blood vessels may lead to intraocular hemorrhage. PMID- 2110448 TI - Coding for surgical audit. AB - A simple system of codes for operations, diagnoses and complications, developed specifically for computerized surgical audit, is described. This arose following a review of our established surgical audit in which problems in the retrieval of data from the database were identified. Evaluation of current methods of classification of surgical data highlighted the need for a dedicated coding system that was suitable for classifying surgical audit data, enabling rapid retrieval from large databases. After 2 years of use, the coding system has been found to fulfil the criteria of being sufficiently flexible and specific for computerized surgical audit, yet simple enough for medical staff to use. PMID- 2110449 TI - Characterization of the cysteine residues and disulphide linkages in the protein crystal of Bacillus thuringiensis. AB - Bacillus thuringiensis produces a 130-140 kDa insecticidal protein in the form of a bipyramidal crystal. The protein in the crystals from the subspecies kurstaki HD-1 and entomocidus was found to contain 16-18 cysteine residues per molecule, present primarily in the disulphide form as cystine. Evidence that all the cysteine residues form symmetrical interchain disulphide linkages in the protein crystal was obtained from the following results: (i) the disulphide diagonal procedure [Brown & Hartley (1966) Biochem. J. 101, 214-228] gave only unpaired cysteic acid peptides in diagonal maps; (ii) the disulphide bridges were shown to be labile in dilute alkali and the crystal protein could be released quantitatively with 1 mM-2-mercaptoethanol; (iii) the thiol groups of the released crystal protein were shown by competitive labelling [Kaplan, Stevenson & Hartley (1971) Biochem. J. 124, 289-299] to have the same chemical properties as exposed groups on the surface of the protein; (iv) the thiol groups in the released crystal protein reacted quantitatively with iodoacetate or iodoacetamide. The finding that all the disulphide linkages in the protein crystal are interchain and symmetrical accounts for its alkali-lability and for the high degree of conservation in the primary structure of the cystine containing regions of the protein from various subspecies. PMID- 2110450 TI - Increased intracellular Ca2+ is necessary for maximal expression of the proto oncogene c-jun in the Jurkat T-cell line. AB - The time course and signal-transduction requirements for proto-oncogene c-jun expression in T-cells were investigated. Expression of c-jun mRNA was evident at 30 min after stimulation. Both the activation of Ca2+/phospholipid-dependent kinase as well as an increased intracellular free Ca2+ concentration were necessary for the maximal induction of c-jun mRNA and synthesis of Jun protein 1 h after stimulation. PMID- 2110451 TI - Guanine nucleotide binding properties of rap1 purified from human neutrophils. AB - The guanine nucleotide binding properties of rap1 protein purified from human neutrophils were examined using both the protein kinase A-phosphorylated and the non-phosphorylated forms of the protein. Binding of GTP[S] (guanosine 5'-[gamma thio]triphosphate) or GDP was found to be slow in the presence of free Mg2+, but very rapid in the absence of Mg2+. The binding of guanine nucleotides was found to correlate with the loss of endogenous nucleotide from the rap1 protein, which was rapid in the absence of Mg2+. The relative affinities of GTP and GDP for the binding site on rap1 were modulated by the presence of Mg2+, with a preferential affinity (approx. 15-fold) for GTP observed only in the absence of this bivalent cation. The dissociation of GDP from rap1 was not affected by the G-protein beta/gamma-subunit complex. Phosphorylation of rap1 in vitro by protein kinase A did not modify any of the observed nucleotide-binding parameters. Furthermore, the ability of a cytosolic rap1 GTPase-activating protein to stimulate neutrophil rap1 GTP hydrolysis was not modified by phosphorylation. These data suggest that the activation of rap in vivo may be regulated by the release of endogenous GDP, but that phosphorylation by protein kinase A does not affect guanine nucleotide binding or hydrolysis. PMID- 2110453 TI - A 1H-NMR study of the solution conformation of Icaria chemotactic peptide and its [Lys7] analog: effects on the physiological activity of a substitution of proline to lysine at position 7. AB - Solution conformations of Icaria chemotactic peptide isolated from the Ropalidian wasp venom and its [Lys7] analog have been analyzed by the use of two-dimensional proton nuclear resonance spectroscopy. It has been shown that Icaria chemotactic peptide takes alpha helical conformation in the C-terminal 8-13 segment with the N-terminal 1-7 segment disordered. By contrast, the [Lys7] analog takes alpha helical conformation over a wider range from residues 3 to 13. The present results indicate that the substitution of proline to lysine at position 7 results in a drastic change in solution conformation, providing the Icaria chemotactic peptide with new physiological functions. PMID- 2110452 TI - The T84 human colonic adenocarcinoma cell line produces mucin in culture and releases it in response to various secretagogues. AB - The T84 colonic adenocarcinoma cell line, which has been used extensively as a model for studies of epithelial chloride secretion, also produces mucin and secretes it in culture. Electron microscopy of fixed sections of cultured cells, along with Immunogold labelling with an antibody to human small intestine (SI) mucin, revealed the presence of goblet-like cells with mucin-containing secretory granules. The mucin was of high molecular mass, had an amino acid composition similar to that of purified human SI and colonic mucins, and competed effectively with SI mucin for binding to the anti-(SI mucin) antibody. A sensitive solid phase immunoassay specific for intestinal mucins was developed and used to measure mucin secretion by T84 cells. Cultures were treated for 30 min at 37 degrees C with a number of agents known to cause chloride secretion by T84 cell monolayers and the amount of mucin appearing in the medium was measured. Carbachol (1 mM), A23187 (10 microM), prostaglandin E1 (PGE1) (1 microM) and vasoactive intestinal polypeptide (VIP) (0.1 microM) all stimulated mucin release, but histamine (1 mM) had no effect. Whereas VIP is reported to stimulate chloride secretion more strongly than carbachol, it was less effective than carbachol in stimulating mucin secretion. Phorbol 12-myristate 13-acetate (PMA) (0.1-10 microM) also stimulated mucin release strongly, implicating a responsive protein-kinase C-dependent pathway. Additive secretory responses were obtained with combined stimulation by VIP (10 nM-1 microM) and carbachol (1 mM). Responses to stimulation with A23187 (1-10 microM) together with PMA (10 nM-10 microM) suggest that cytosolic Ca2+ concentration is a modulator of PMA activity. PMID- 2110454 TI - Immunolocalization of C1-tetrahydrofolate synthase in the rat kidney. AB - The distribution of the trifunctional enzyme C1-tetrahydrofolate synthase (C1-THF synthase) was examined in the rat kidney by immunolocalization with anti-C1-THF synthase serum using the peroxidase-antiperoxidase method. C1-THF synthase immunoreactivity was detected in both distal and proximal epithelial cells. Staining of the distal tubule epithelia was more intense and granular whereas staining of the proximal tubule epithelia was diffuse. All cells of the cortical collecting duct showed positive granular staining. In the outer medullary collecting duct, the intercalated cells showed intense granular cytoplasmic staining and the principal cells were either negative or weakly positive. The ascending thick limb of Henle's loop was also positive. Glomeruli and the inner medulla showed no staining for C1-THF synthase. PMID- 2110455 TI - Estrogen induced expression of the C-jun proto-oncogene in the immature and mature rat uterus. AB - The expression of the proto-oncogene c-jun in response to estradiol treatment in immature and mature rat uterine tissue was measured using a cDNA encoding the mouse c-jun proto-oncogene. This probe hybridized to a major RNA band of 2.7 kb and a minor 3.2 kb band. In Northern blots of total RNA from both immature and mature rat uteri, estradiol treatment resulted in at least a 3 fold increase in expression of the 2.7 kb band over control levels by 3 hr post injection. By 12 hr post injection, expression of c-jun mRNA had returned to control levels. A strong induction (greater than 5 fold) of c-jun mRNA expression was also observed in stroma-myometrial tissue isolated from mature rats approximately 3 hours after treatment with estradiol. The similar kinetics of induction of c-fos and c-jun emphasizes the functional significance of the fos/jun heterodimer in control of uterine cell proliferation. PMID- 2110456 TI - Human acid beta-glucosidase: glycosylation is required for catalytic activity. AB - The role of oligosaccharide modification in human acid beta-glucosidase function was investigated. This lysosomal enzyme has five putative N-glycosylation sites, four of which are occupied. The unglycosylated human protein was stable when expressed in bacteria or in Spodoptera frugiperda cells in the presence of tunicamycin but lacked catalytic activity. Deglycosylation of purified acid beta glucosidase from human placenta with N-Glycanase under native conditions resulted in the removal of an accessible oligosaccharide chain from a single site with no effect on activity, whereas complete deglycosylation resulted in proportionate loss of activity. These studies demonstrate that occupancy of at least one glycosylation site is required for the formation and maintenance of acid beta glucosidase in an active conformation. PMID- 2110457 TI - Intravascular big endothelin increases circulating levels of endothelin-1 and prostanoids in the rabbit. PMID- 2110458 TI - Development of radioimmunoassay for a potent luteinizing hormone-releasing hormone antagonist. Evaluation of serum levels after injection of [Ac-3-(2 naphthyl)-D-Ala1, D-Phe(pCl)2, 3-(3-pyridyl)-D-Ala3, D-Cit6, D-Ala10] LHRH. AB - Highly potent antagonistic analogs of luteinizing hormone-releasing hormone (LHRH), free of edematogenic effects have been developed. These analogs proved to be potent inhibitors of LH, follicle stimulating hormone (FSH) and sex steroid levels in animals and human beings. The clinical utility of these compounds would be greatly enhanced by a sustained delivery system, capable of maintaining therapeutic peptide levels in blood over an extended period of time. Consequently, long acting formulations of microcapsules were prepared from one of the most potent antagonists, [Ac-3-(2-naphthyl)-D-Ala1, D-Phe (pCl)2, 3-(3 pyridyl)-D-Ala3, D-Cit6, D-Ala10] LHRH (SB-75). The microcapsules consisted of 2% w/w SB-75 in poly-DL-lactide-co-glycolide (PLGA), a biocompatible, biodegradable polymer. To facilitate pharmacokinetic studies necessary for experimental and clinical investigation of the microencapsulated analog, a highly sensitive and specific radioimmunoassay was developed. The antibody against SB-75 was generated in rabbits. No significant cross-reaction could be detected with several natural peptides and analogs tested. The sensitivity of the assay is 0.6 pg/tube. The RIA is suitable for direct determination of SB-75 level in 20 microliters serum. The two lots of SB-75 microcapsules exhibited different pharmacokinetic release patterns. Single intramuscular injection of 20 mg SB-75 microcapsules, PLGA batch No. 001, into female rats maintained elevated serum SB-75 levels for three weeks. The suppression of LH secretion during this period was indicated by histological findings. The ovaries in the treated group were polyfollicular and no corpora lutea were present, indicating a prolonged ovarian inactivity due to LH deprivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110459 TI - Effect of schistosomiasis infection on the clearance of phenazone in mice. AB - The disposition phenazone (antipyrine) was used to study the effect of Schistosoma mansoni infection on the activity of drug metabolizing enzymes in mice. Plasma elimination rate constant (Ke), elimination half-life (t1/2e), clearance (CL) and apparent volume of distribution (Vd) were estimated 8 and 12 weeks after infection of mice with 80 S. mansoni cercariae. Liver and kidney function tests were performed simultaneously. Infection increased the levels of glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), alkaline phosphatase (AP) and total proteins 8 and 12 weeks post infection. At the same time a decrease was recorded in the total cholesterol level. Moreover infection with S. mansoni produced a decrease in phenazone clearance with an increase in the area under the curve (AUC) of the drug 8 and 12 weeks post infection. Elimination half-lives were 57.92 +/- 14.10 and 72.72 +/- 4.14 min 8 and 12 weeks after infection, respectively, compared to 19.29 +/- 3.30 and 26.14 +/- 5.31 min in corresponding controls. No statistically significant change was recorded in the volume of distribution of phenazone in the groups studied. In addition no significant correlation was found between parameters of phenazone disposition and the enzyme levels studied 8 and 12 weeks after infection. PMID- 2110460 TI - Dissection of an inflammatory process induced by CD8+ T cells. AB - A massive delayed type hypersensitivity (DTH) reaction occurs in the cerebrospinal fluid (CSF) of mice with lymphocytic choriomeningitis (LCM). In this article, Peter Doherty and colleagues analyze this reaction together with the population dynamics of the regional lymph node to give a comprehensive picture of the events underlying this CD8+ T-cell-mediated immunopathological disease. Their findings are of general relevance to the understanding of inflammation. PMID- 2110461 TI - Bacterial toxin vaccines. PMID- 2110462 TI - Production and control of Neisseria meningitidis vaccines. PMID- 2110463 TI - Chronic liver disease in haemophiliacs. PMID- 2110465 TI - Arachidonic acid metabolism in platelets stored for 5 days. AB - (C-14)-Arachidonic acid [(C-14)-AA] metabolism was studied in platelet concentrates (PCs) stored for 5 d. There was a gradual decrease in uptake of radioactivity from day 0 to 3 (P less than 0.01). On day 0, distribution of radioactivity in platelet phospholipids (PLs), and formation of phosphatidic acid, HETE and cyclooxygenase products, when platelets were exposed to thrombin (5 U/ml), were similar to that reported for fresh platelets. On day 3 there was a change in the distribution of (C-14)-AA in platelet PLs which consisted of an increase in the percentage of radioactivity bound to phosphatidylserine, from 5.3 +/- 0.9% on day 0 to 8.8 +/- 1.5% on day 3 (P less than 0.001), and a decrease in (C-14)-AA in phosphatidylinositol (PI), from 12.4 +/- 1.5% on day 0, to 7.9 +/- 0.9% on day 3 (P less than 0.001). Phosphatidic acid generated by thrombin stimulated platelets on day 0, comprised 2.6 +/- 0.5% of total radioactivity, but dropped to 1.4 +/- 0.3% on day 3 (P less than 0.001), and 0.9 +/- 0.2% on day 5 (P less than 0.01). These values showed a good correlation with the percentage of (C-14)-AA released from PI on the same days (r = 0.9). On day 0, 13.4 +/- 4.4% of platelet radioactivity was released from phosphatidylcholine by thrombin, but this amount was reduced to 6.8 +/- 3.4% on day 5 (P less than 0.05). Generation of radioactive 12-hydroxy-5,8,10,14-eicosatetraynoic acid (HETE) also dropped from 7.2 +/- 2.9 on day 0, to 2.1 +/- 1 on day 5 (P less than 0.01). We could not detect changes in cyclooxygenase metabolites. In conclusion, we suggest that various enzymatic pathways implicated in AA metabolism by platelets are impaired by storage. PMID- 2110464 TI - Elevated white blood cell synthesis of leukotriene C4 in chronic myelogenous leukaemia but not in polycythaemia vera. AB - Leukotriene (LT) formation was studied in ionophore A23187-stimulated white blood cell (WBC) preparations from patients with chronic myelogenous leukaemia (CML; n = 14), polycythaemia vera (PV; n = 10) and two control groups consisting of patients with non-malignant inflammatory disease (n = 4) and normal healthy donors (n = 25). The synthesized products were identified and quantitated using high-performance liquid chromatography combined with computerized UV spectroscopy. White blood cell preparations from the CML patients produced more LTC4 (40.2 +/- 7.9 pmol/10(6) WBC, mean +/- SEM) than WBC from the healthy donors (9.0 +/- 1.8), P less than 0.0005. In contrast, the formation of LTB4 was normal and there was no increase in the total leukotriene synthesis (the sum of LTC4, LTB4, 20-OH-LTB4 and the delta 6-trans-isomers of LTB4). The ratio between leukotrienes C4 and B4 was strongly elevated in the CML group; 1.67 +/- 0.25 v. 0.37 +/- 0.07 in the controls, P less than 0.0005. No significant correlation was observed between the levels of LTC4 and the number of known LTC4 producing cells (such as monocytes, eosinophils and basophils) in the CML WBC preparations. In contrast, a correlation was found between the sum of neutrophilic granulocytes and metamyelocytes in these suspensions and the amount of LTB4 formed; r = 0.600, P less than 0.05. A number of other laboratory or clinical variables of the CML patients (including total white blood cell and platelet counts, differential counts, previous cytotoxic treatment, time from diagnosis, time from last treatment, post study survival and age) did not significantly correlate with the formation of leukotrienes. No abnormality in the production of LTB4 or LTC4 was observed in granulocyte and WBC preparations from the patients with polycythaemia vera and non-malignant inflammatory disease, respectively. The results indicate a selectively increased LTC4 producing capacity in CML. PMID- 2110466 TI - Elevated platelet-free calcium in uraemia. AB - Bleeding complications in uraemia are not uncommon. The pathogenesis of haemorrhage in uraemia is still a matter of controversy and the pattern of bleeding suggests a defect of primary haemostasis. Platelet aggregation and biochemistry, including calcium levels, have been studied; however, the results are controversial. We have examined platelet aggregation, platelet-free calcium and calmodulin in platelet-rich plasma because of the significant role of calcium and calmodulin in regulating platelet and other cells' functions. Platelet aggregation in uraemic subjects was similar to that of controls. Platelet basal free cytosolic calcium and platelet calcium in response to 10 microM Ca++ ionophore A23187 in eight subjects with uraemia were 117 +/- 33 nM and 2025 +/- 398 nM (mean +/- SEM) respectively. By contrast in seven matched healthy controls basal calcium and ionophore-stimulated calcium values were 47 +/- 14 nM and 1354 +/- 414 nM, significantly less than in the patients with uraemia (P less than 0.05). The sensitivity of uraemic platelets to A23187 was similar to that of controls. Calmodulin activity in platelet-rich plasma of 12 subjects with uraemia showed no significant difference from that of controls [1.86 +/- 0.29 micrograms/ml (mean +/- SEM) and 2.0 +/- 0.37 micrograms/ml (mean +/- SEM) respectively]. We conclude that despite elevation of platelet calcium in uraemia, which may be due to a plasma factor such as parathyroid hormone, platelet aggregation is normal and bleeding in uraemia is more likely to be due to other factors, including the effect of reduced haematocrit on platelet endothelial interaction. Disturbances in platelet calcium cannot explain the bleeding manifestations in uraemia but warrant further investigation in order to identify the pathogenic mechanisms responsible. PMID- 2110467 TI - Osteopenia in pregnancy during long-term heparin treatment: a radiological study post partum. AB - Osteopenia, sometimes with compression fractures of the spine, is a side-effect of long-term heparin treatment. The frequency is unknown. In this study, 70 women were given subcutaneous heparin as therapy for, or prophylaxis against, thromboembolism during pregnancy. All, except two, were examined by X-ray of the spine and hip first week post partum. The duration of treatment and the dosage of heparin varied. There were 12 (17%) with obvious osteopenia, including two women with multiple fractures of the spine (3%). Re-examination 6-12 months post partum showed that the changes were reversible in most cases. Another 18 women were examined about three years after heparin treatment during pregnancy. No obvious osteopenia was found among them or in a control group of 30 women examined in the first week post partum. The degree of osteopenia was not correlated with either the heparin dose or the duration of treatment. Women treated with heparin in consecutive pregnancies do not seem to have an increased risk of osteopenia. PMID- 2110468 TI - Adaptation to a marginal intake of energy in young children. AB - Six male children, aged 8-28 months, were studied for three consecutive periods of 1 week each. They were given diets that provided 1.7 g protein/kg per d and supplements of minerals and vitamins, with a metabolizable energy intake during the 1st, 2nd and 3rd week of 419, 293 and 335 kJ (100, 70 and 80 kcal)/kg per d, diets 1, 2 and 3 respectively. All the food offered was consumed. Each child was weighed at the same time each day on an electronic balance. On the 6th and 7th day of each study period urine and stool were collected for 24 h to assess nitrogen balance. Using linear regression analysis it was shown that all children gained weight on diet 1, 2.3 (SD 1.3) g/kg per d, and five of six children gained weight on diet 3, the mean for the whole group being 2.7 (SD 2.3) g/kg per d, not significantly different. On diet 2 all children lost weight, -5.4 (SD 1.3) g/kg per d, highly significantly different from each of the other dietary periods. Using asymptotic regression analysis it could be shown that the rate of weight loss during the first part of the week on diet 2, -11 g/kg per d, was greater than at the end of the week, -2 g/kg per d, with a tendency towards a steady weight by day 7. Apparent N retention (mg/kg per d) was positive at the end of each of the three dietary periods: diet 1, 112 (SD 25); diet 2, 54 (SD 34); diet 3, 82 (SD 20). In five of the six children there was a marked reduction in stool frequency on diet 2 compared with diet 1, that was maintained to the period on diet 3. The findings suggest that during the period on diet 2 there was a saving of energy of the order of 105 kJ (25 kcal)/kg per d, which lasted through into the period on diet 3. PMID- 2110469 TI - Dependence of the carbon-isotope contents of breath carbon dioxide, milk, serum and rumen fermentation products on the delta 13C value of food in dairy cows. AB - Six dairy cows of two breeds were fed during three alternating periods with products from C3- and C4- plants to yield different natural 13C enrichments of the diet (delta 13C range: -28.0 to -13.7%). The resulting changes in the 13C enrichment of breath carbon dioxide, serum and milk of the animals followed the 13C:12C of the food, in agreement with the individual biological half-lives of those products, and established isotope discriminations. Breath CO2 was more enriched in 13C than expected. This could be related to isotope discriminations during rumen fermentation. From these results an isotopic balance model for the breath CO2 could be established. PMID- 2110470 TI - Excretion of purine derivatives by ruminants: recycling of allantoin into the rumen via saliva and its fate in the gut. AB - The saliva of sheep was shown to contain significant concentrations of uric acid (16(SD 4.5) mumol/l) and allantoin (120(SD 16.4) mumol/l), sufficient to recycle purine derivatives equivalent to about 0.10 of the normal urinary excretion. When allantoin was incubated in vitro in rumen fluid, it was degraded at a rate sufficient to ensure complete destruction of recycled allantoin. In a series of experiments in which allantoin was infused into the rumen of sheep fed normally, or into the rumen or abomasum of sheep and the rumen of cattle completely nourished by intragastric infusion of volatile fatty acids and casein, no additional allantoin was recovered in the urine. These losses were probably due to the degradation of allantoin by micro-organisms associated with the digestive tract. It is concluded that all allantion and uric acid recycled to the rumen via saliva will be similarly degraded. Therefore, the use of urinary excretion of purine derivatives as an estimator of the rumen microbial biomass available to ruminants will need to be corrected for such losses. PMID- 2110471 TI - Distinction between the two basic mechanisms of cation transport in the cardiac Na(+)-Ca2+ exchange system. AB - In order to distinguish between the Ping-Pong and sequential mechanisms of cation transport in the cardiac Na(+)-Ca2+ exchange system, the initial rates of the Nai dependent 45Ca uptake (t = 1 s) were measured in reconstituted proteoliposomes, loaded with a Ca chelator. Under "zero-trans" conditions ([Na]o = [Ca]i = 0) at a fixed [Na]i = 10-160 mM with varying [45Ca]o = 2.5-122 microM for each [Na]i, the Km and Vmax values increased from 7.7 to 33.5 microM and from 2.3 to 9.0 nmol.mg 1.s-1, respectively. The Vmax/Km values show a +/- 2-10% deviation from the average value of 0.274 nmol.mg-1.s-1.microM-1 over the whole range of [Na]i. These deviations are within the standard error of Vmax (+/- 3-7%), Km (+/- 11 17%), and Vmax/Km (+/- 11-19%). This suggests that, under conditions in which Vmax and Km are [Na]i dependent and vary 4-5-fold, the Vmax/Km values are constant within the experimental error. In the presence of K(+)-valinomycin the Vmax/Km values are 0.85 +/- 0.17 and 1.08 +/- 0.18 nmol.mg-1.s-1.microM-1 at [Na]i = 20 and 160 mM, respectively, suggesting that under conditions of "short circuit" of the membrane potential the Vmax/Km values still exhibit the [Na]i independence. At a very low fixed [45Ca]o = 1.1 microM with varying [Na]i = 10 160 mM, the initial rates were found to be [Na]i independent. At a high fixed [45Ca]o = 92 microM the initial rates show a sigmoidal dependence on the [Na]i with Vmax = 13.8 nmol.mg-1.s-1, KmNa = 21 mM, and Hill coefficient nH = 1.5. The presented data support a Ping-Pong (consecutive) mechanism of cation transport in the Na(+)-Ca2+ exchanger. PMID- 2110472 TI - pH dependence of the urea and guanidine hydrochloride denaturation of ribonuclease A and ribonuclease T1. AB - To investigate the pH dependence of the conformational stability of ribonucleases A and T1, urea and guanidine hydrochloride denaturation curves have been determined over the pH range 2-10. The maximum conformational stability of both proteins is about 9 kcal/mol and occurs near pH 4.5 for ribonuclease T1 and between pH 7 and 9 for ribonuclease A. The pH dependence suggests that electrostatic interactions among the charged groups make a relatively small contribution to the conformational stability of these proteins. The dependence of delta G on urea concentration increases from about 1200 cal mol-1 M-1 at high pH to about 2400 cal mol-1 M-1 at low pH for ribonuclease A. This suggests that the unfolded conformations of RNase A become more accessible to urea as the net charge on the molecule increases. For RNase T1, the dependence of delta G on urea concentration is minimal near pH 6 and increases at both higher and lower pH. An analysis of information of this type for several proteins in terms of a model developed by Tanford [Tanford, C. (1964) J. Am. Chem. Soc. 86, 2050-2059] suggests that the unfolded states of proteins in urea and GdnHCl solutions may differ significantly in the extent of their interaction with denaturants. Thus, the conformations assumed by unfolded proteins may depend to at least some extent on the amino acid sequence of the protein. PMID- 2110473 TI - Kinetics of coagulation factor X activation by platelet-bound factor IXa. AB - Thrombin-activated human platelets, in the presence of factors VIIIa and X, have specific, high-affinity (Kd approximately 0.5 nM), saturable binding sites for factor IXa that are involved in factor X activation [Ahmad, S.S., Rawala-Sheikh, R., & Walsh, P.N. (1989) J. Biol. Chem. 264, 3244-3251]. To determine the functional consequences of factor IXa binding to platelets, a detailed kinetic analysis of the effects of platelets, phospholipids, and factor VIII on factor IXa catalyzed factor X activation was done. In the absence of platelets, phospholipids, or factor VIII, the Michaelis constant (Km = 81 microM) was greater than 500-fold higher than the factor X concentration in human plasma. Unactivated platelets and thrombin-activated factor VIII, alone or in combination, had no effect on the kinetic parameters, whereas thrombin-activated platelets caused a major decrease in Km (0.39 microM) with no significant effect on kcat (0.052 min-1) and allowed factor VIIIa to decrease the Km further to a concentration (0.16 microM) near that of factor X in plasma and to increase the kcat 24,000-fold to 1240 min-1. Sonicated mixed phosphatidylserine/phosphatidylcholine vesicles (25/75, mol/mol) had kinetic effects similar to those of activated platelets. When factor IXa binding to thrombin-activated platelets and rates of factor X activation were measured simultaneously at saturating concentrations of factor X and factor VIIIa, the kcat was independent of factor IXa concentration, and the mean kcat value was 2391 min-1. The increase in catalytic efficiency (kcat/Km) in the presence of thrombin-activated platelets and factor VIIIa was (17.4 x 10(6))-fold. PMID- 2110474 TI - Fourier transform infrared difference spectroscopy shows no evidence for an enolization of chlorophyll a upon cation formation either in vitro or during P700 photooxidation. AB - Molecular changes associated with the photooxidation of the primary electron donor P700 in photosystem I from cyanobacteria have been investigated with Fourier transform infrared (FTIR) difference spectroscopy. Highly resolved signals are observed in the carbonyl stretching frequency region of the light induced FTIR spectra. In order to assign and to interpret these signals, the FTIR spectra of isolated chlorophyll a and pyrochlorophyll a (lacking the 10a-ester carbonyl) in both their neutral and cation states were investigated. Comparison of the redox-induced FTIR difference spectra of these two model compounds demonstrates that upon chlorophyll a cation formation in tetrahydrofuran the 7c ester carbonyl is essentially unperturbed while the 10a-ester carbonyl is upshifted from 1738 to 1751 cm-1. For the 9-keto group, the shift is from 1693 to 1718 cm-1 in chlorophyll a and from 1686 to 1712 cm-1 in pyrochlorophyll a. The 1718-cm-1 band in the difference spectrum of chlorophyll a is thus unambiguously assigned to the 9-keto carbonyl of the cation. Comparison of the light-induced FTIR difference spectrum associated with the photooxidation of P700 in vivo with the difference FTIR spectrum of chlorophyll a cation formation leads to the assignment of the frequencies of the 9-keto carbonyl group(s) at 1700 cm-1 in P700 and at 1717 cm-1 in P700+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110475 TI - Interaction of myosin subfragment 1 with fluorescent ribose-modified nucleotides. A comparison of vanadate trapping and SH1-SH2 cross-linking. AB - The environment near the ribose binding site of skeletal myosin subfragment 1 (S1) was investigated by use of two adenosine 5'-diphosphate analogues with fluorescent groups attached at the 2'- and 3'-hydroxyls of the ribose ring. We have compared steady-state and time-resolved fluorescent properties of the reversibly bound S1-nucleotide complexes and the complexes generated by N,N'-p phenylenedimaleimide (pPDM) thiol cross-linking or vanadate (Vi) trapping. A new fluorescent probe, 2'(3')-O-[N-[2-[[[5-(dimethylamino)naphthyl]sulfonyl] amino]ethyl]carbamoyl]adenosine 5'-diphosphate (DEDA-ADP), which contains a base stable carbamoyl linkage between the ribose ring and the fluorescent dansyl group, was synthesized and characterized. For comparison, we performed parallel experiments with 2'(3')-O-(N-methylanthraniloyl)adenosine 5'-diphosphate (MANT ADP) [Hiratsuka, T. (1983) Biochim. Biophys. Acta 742, 496-508]. Solute quenching studies indicated that both analogues bound reversibly to a single cleft or pocket near the ribose binding site. However, steady-state polarization measurements indicated that the probes were not rigidly bound to the protein. The quantum yields of both fluorophores were higher for the complexes formed after trapping with pPDM or Vi than for the reversibly bound complexes. Both DEDA-ADP and MANT-ADP, respectively, had nearly homogeneous lifetimes free in solution (3.65 and 4.65 ns), reversibly bound to S1 (12.8 and 8.6 ns), and trapped on S1 by pPDM (12.7 and 8.7 ns) or Vi (12.8 and 8.6 ns). In contrast to the quantum yields, the lifetimes were not increased upon trapping, compared to those of the reversibly bound states. These results suggested that static quenching in the reversibly bound complex was relieved upon trapping. Taken together, the results suggest that there was a conformational change near the ribose binding site upon trapping by either pPDM or Vi. On the basis of the quantum yield, lifetime, polarization, and solute accessibility studies, we could not detect differences between the S1-pPDM-nucleotide analog complex and the S1-Vi-nucleotide analogue complex for either analogue. Thus, previously observed differences with the adenine modified nucleotide analogue 1,N6-ethenoadenosine diphosphate (epsilon ADP) could not be detected with these ribose-modified probes, indicating that structural differences may be localized to the adenine binding site and not transmitted to the region near the ribose ring. PMID- 2110476 TI - Drug binding by branched DNA: selective interaction of the dye stains-all with an immobile junction. AB - The thiacarbocyanine dye Stains-All (4,5:4',5'-dibenzo-3,3'-diethyl-9 methylthiacarbocyanine bromide) is one of a large number of cyanine dyes introduced as photosensitizers in the photographic industry. Stains-All is used in histology as a stain for nucleic acids, proteins, polysaccharides, and lipids. We report here that the dye colors branched DNA molecules differently from linear duplexes and use footprinting experiments with methidiumpropyl-EDTA-Fe(II) [MPE.Fe(II)] and bis(o-phenanthroline)copper(I) [(O-P)2Cu(I)] to show that Stains All interacts preferentially at the branch point of a four-arm DNA structure. A titration experiment allows us to estimate that the interaction of the dye with the branch has a dissociation constant below 45 nM, tighter than that of ethidium or methidium by over 2 orders of magnitude. Probing the interaction with the purine-specific reagent diethyl pyrocarbonate (DEPC) implies that the dye induces an asymmetric distortion near the branch in the major grooves of double helix in the junction. PMID- 2110477 TI - Iron(II)-ethylenediaminetetraacetic acid catalyzed cleavage of RNA and DNA oligonucleotides: similar reactivity toward single- and double-stranded forms. AB - Fe(II)-EDTA catalyzes the cleavage of nucleic acids with little or no base sequence specificity. We have now studied the preference of this reagent in catalyzing the cleavage of single- versus double-stranded nucleic acid structures. Three RNA and two DNA molecules, each expected to contain both single and double-stranded regions, were synthesized and their structures characterized by enzymatic digestion using secondary structure specific nucleases. Fe(II)-EDTA catalyzed nearly uniform strand scission along the entire length of each molecule; no correlation with secondary structure was observed. The homopolymer sequence dA30:dT30, embedded in a mixed-sequence context to promote exact register of the homopolymer tract, was cleaved to an extent similar to that of flanking sequences. The reactions were relatively insensitive to K+, Na+, and Mg2+ in the range 10-100 mM and were quenched by Tris-HCl buffer. We conclude that the Fe(II)-EDTA-catalyzed strand scission reaction does not discriminate between typical single- and double-stranded regions, which simplifies the interpretation of experiments in which the reaction is used to probe the tertiary structure of RNA molecules [Latham, J. A., & Cech, T. R. (1989) Science 245, 276 282]. PMID- 2110478 TI - A comparison of strategies to stabilize immunoglobulin Fv-fragments. AB - Fv-Fragments of antibodies may dissociate at low protein concentrations and are too unstable for many applications at physiological temperatures. To stabilize Fv fragments against dissociation, we have tested and compared three different strategies on the Fv-fragment of the well-characterized phosphocholine binding antibody McPC603 expressed and secreted in Escherichia coli: chemical cross linking of the variable domains, introduction of an intermolecular disulfide bond, and construction of a peptide linker to produce a "single-chain" Fv fragment. All the linked fragments show hapten affinities nearly identical with that of the whole antibody independent of protein concentration and are significantly (up to 60-fold) stabilized against irreversible thermal denaturation. All genetically engineered linked Fv-fragments can be obtained in native conformation in E. coli. The reported strategies for generating Fv fragments with improved physicochemical properties may extend their usefulness in biotechnology as well as in therapeutic and diagnostic applications. PMID- 2110479 TI - Metabolic depletion effect on serine/threonine- and tyrosine-phosphorylations of membrane proteins in human erythrocytes. AB - The response of serine/threonine-phosphorylation of the major transmembrane protein (band 3) in human erythrocytes to the metabolic state of the cells is different from that exhibited by the tyrosine-phosphorylation of the same protein. Precisely, both serine- and tyrosine-phosphorylation are decreased during metabolic depletion of the erythrocytes. However, the depletion-induced tyrosine-phosphorylation decrease of band 3 is not reversed by the subsequent metabolic repletion of the depleted cells, being accompanied by an irreversible inactivation of both membrane-bound and cytosolic tyrosine-protein kinase(s). By contrast, the depletion-induced phosphoserine-dephosphorylation is reversed by the following repletion, being accompanied by a reversible translocation of casein kinase(s) between cytosolic and membrane compartments. A possible functional correlation between the serine-phosphorylation state of band 3 protein and the band 3-mediated anion transport across the membrane is discussed. PMID- 2110480 TI - Mechanisms of delivery of liposome-encapsulated cytosine arabinoside to CV-1 cells in vitro. Fluorescence-microscopic and cytotoxicity studies. AB - Fluorescence microscopy and assays of the cytotoxicity of liposome-encapsulated cytosine arabinoside (araC) have been used to examine the interactions of CV-1 cells with pH-sensitive liposomes, combining phosphatidylethanolamine (PE) with oleic acid or with double-chain protonatable amphiphiles, and with pH-insensitive liposomes combining phosphatidylcholine (PC) and phosphatidylglycerol (PG). Fluorescence-microscopic observations indicate that double-chain protonatable amphiphiles remain tightly associated with pH-sensitive liposomes during incubations with CV-1 cell monolayers, and that cellular uptake of liposomes is strongly promoted by transferrin coupled to the liposome surface. Liposome encapsulated araC showed much greater cytotoxicity toward CV-1 cells than did the free drug at equivalent concentrations under the same conditions. The cytotoxicity of encapsulated araC was strongly enhanced by liposome-conjugated transferrin and was maximal using pH-sensitive liposomes combining PE with the double-chain protonatable amphiphile N-(N'-oleoyl-2-aminopalmitoyl)serine. However, the drug was also markedly more cytotoxic when encapsulated in other types of transferrin-conjugated liposomes, including pH-insensitive PC/PG/cholesterol liposomes, than in the free form. The cytotoxicity of liposome encapsulated araC is significantly attenuated by the nucleoside transport inhibitor nitrobenzothioinosine, and fluorescence microscopy using calcein containing liposomes provides no evidence for efficient fusion between cellular membranes and any of the types of liposomes examined here. Based on these observations, we suggest that the major mechanism for cytoplasmic delivery of liposome-encapsulated araC is the carrier-mediated transport of drug that has been released from liposomes into the endosomal and/or the lysosomal compartments. PMID- 2110481 TI - Phenylmethylsulfonyl fluoride protects L-lysine transport in Schizosaccharomyces pombe against inactivation by ammonium ions. AB - Ammonium ions inactivate the basic amino acid transport system in Schizosaccharomyces pombe in an irreversible manner. The inactivation is accompanied by a 4-fold decrease of KT of L-lysine transport, leaving its Jmax unchanged; phenylmethylsulfonyl fluoride protects the system against inactivation. In contrast, two basic amino acid transport systems in a gap1 mutant of Saccharomyces cerevisiae are influenced by NH4+ ions in such a way that only the Jmax decreases while the KT of L-lysine transport is unchanged. Phenylmethylsulfonyl fluoride does not act here as a protective agent. PMID- 2110482 TI - Modulation of Na+/alanine cotransport in liver sinusoidal membrane vesicles by internal divalent cations. AB - Rat liver basolateral plasma membrane (blLPM) vesicles resuspended in 5 mM Mg2(+) , Ca2(+)-, Mn2(+)- or Co2(+)-containing media exhibited a markedly lower rate of Na(+)-stimulated L-alanine transport. Divalent cation inhibition of L-alanine uptake was dose dependent, and was observed only when the vesicles were pre loaded with the divalent cations. The presence or absence of the metal ions in the extravesicular incubation media had no effect on L-alanine transport. Conversely, pretreatment of the vesicles with 0.2 mM of either EGTA or EDTA resulted in higher initial rates of L-alanine transport. This stimulation was overcome by addition of excess divalent cation to the vesicle suspension solution. Since these blLPM vesicles are primarily oriented right-side-out, the divalent cation inhibition of L-alanine transport appears to be a result of their interaction with cytosolic components of the cell membrane. Total Na+ flux as measured with 22Na+ was not affected by intravesicular 5 mM Mg2+ or Ca2+, indicating that the inhibition was not due to dissipation of the Na+ gradient. These observations suggest that intracellular divalent cations may serve to modulate L-alanine transport across the liver cell plasma membrane. PMID- 2110483 TI - Isolated adipocytes from growth hormone-treated obese (ob/ob) mice exhibit insulin resistance. AB - The genetically obese (ob/ob) mouse is a useful model for the study of the diabetogenic action of growth hormone (GH), because treatment of these animals with GH results in decreased responsiveness of their adipose tissue to insulin in vitro. Studies of the mechanisms involved in GH-induced insulin resistance using isolated adipocytes of ob/ob mice have not been possible, however, because of their extreme fragility and the lack of an adequate system for the maintenance of these cells. This study describes a new method for the isolation of ob/ob mouse adipocytes. The isolated cells are stable, viable and metabolically responsive to insulin. In addition, these adipocytes have been maintained in primary culture, in serum-free medium, for up to 3 days. During culture, the cells exhibit large increases in 125I-hGH binding (10-20-fold) and porcine 125I-insulin binding (5-10 fold). The induction of insulin resistance by GH has also been demonstrated in these freshly isolated ob/ob mouse adipocytes. The studies to date indicate that the ob/ob mouse adipocyte system should provide a useful model for detailed studies of the cellular and molecular mechanisms of GH induced insulin resistance. PMID- 2110484 TI - G-protein subunit mRNA levels in rat heart, liver, and adipose tissues: analysis by DNA-excess solution hybridization. AB - The steady-state levels of mRNAs for the G-proteins Gi alpha 2, Go alpha, and the G beta-subunits common to each were established in rat adipose, heart and liver. Uniformly-radiolabeled, single-stranded antisense probes were constructed from cDNAs or assembled from oligonucleotides. Direct comparison of the steady-state levels of the G-protein mRNAs was performed under identical assay conditions, and on a molar basis. In adipose, liver and heart, Gs alpha mRNA was more abundant than mRNA for Go alpha, Gi alpha, and G beta. In adipose tissue, mRNA levels were as follows: 19.4, 7.6, 7.0, and 2.3 amol mRNA per micrograms total cellular RNA for Gs alpha, G beta, Gi alpha 2, and Go alpha, respectively. In heart Gs alpha mRNA was less abundant than in adipose, but the relative trend among the G protein subunits was the same. In liver, G beta mRNA was more abundant than either Go alpha or Gi alpha 2. Go alpha mRNA levels ranged from 1.2 to 2.3 amol/micrograms total RNA in liver and adipose, respectively. The present work demonstrates the many advantages of this strategy when applied to the study of a family of homologous, low-abundance proteins and establishes for the first time the molar levels of Gi alpha 2, Gs alpha, Go alpha, and G beta-subunit mRNAs in several mammalian tissues. PMID- 2110485 TI - Disturbances in the hypothalamo-pituitary-adrenal and other neuroendocrine axes in bulimia. AB - Disturbances in the hypothalamo-pituitary-adrenal (HPA) and other endocrine axes were assessed in 24 women with bulimia and healthy controls. Overnight blood samples for measuring nocturnal plasma cortisol, prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were obtained at 30-min intervals. A 1.5 mg dexamethasone suppression test (DST) and a TRH-test were performed. Patients were monitored closely while their nutritional intake was recorded over 21 days. Compared with healthy controls, nocturnal cortisol plasma levels were not elevated in the bulimics. There was a trend toward insufficient cortisol suppression in the DST in patients with bulimia, which was most pronounced in patients with signs of restricted caloric intake. Plasma dexamethasone levels were significantly reduced in bulimics compared with healthy controls. There was a trend for blunted thyrotropin stimulating hormone (TSH) responses to thyrotropin releasing hormone (TRH) in bulimia. The prolactin response to TRH was significantly reduced in bulimics with a history of anorexia nervosa. Plasma LH and plasma FSH were significantly reduced in bulimics with signs of reduced caloric intake [low T3, high levels of beta-hydroxy-butyric acid (BHBA), reduced daily caloric intake, high number of fasting days] as compared with healthy controls. Bulimics with high BHBA levels had significantly reduced nocturnal prolactin plasma levels. Results show that multiple neuroendocrine disturbances exist in bulimia in a milder form than in anorexia nervosa. Evidence for the impact of caloric intake on endocrine functions is presented. Endocrine dysfunctions in our bulimic sample did not show a positive association with the presence of depressive symptoms. PMID- 2110486 TI - [Sympathetic and parasympathetic regulation of the heart in transitory coronary insufficiency]. AB - Experiments were made on 480 rats and 60 rabbits with transitory insufficiency (duration of myocardial ischemia 10.40 and 120 min the length of subsequent reperfusion 40-60 min). It was discovered that there was natural development of the phenomenon of limitation of drawing the heart in direct and reflectory reactions of the circulation system within the increase of duration of local ischemia and the beginning of the subsequent reperfusion. The phenomenon of "limitation", which is realized with the involvement of sympathetic and parasympathetic mechanisms, promotes a decrease of the extent of heart alteration during its local ischemia and increase of reparative process in the heart at the reperfusion period. PMID- 2110487 TI - [Role of noradrenaline of the dorsal hippocampus in the mechanism of self stimulation reaction in rats]. AB - In has been established that intrahippocampal bilateral injection of NA did not influence common frequency of lateral hypothalamic self stimulation. After the destruction of hippocampal NA - terminals of 6-OHDA increased the frequency of self stimulation and rearing. It is suggested that NA hippocampus inhibit the recall trace of the memory of sensory reinforcement stimuli in the course of stimulation "reward". PMID- 2110488 TI - [Isolation and characterization of cells from primary culture of rat kidney glomeruli]. AB - The optimal method to obtain primary rat glomerular cell culture was developed. The method includes isolation of rat glomeruli by pressing slices of renal cortex through sieves, treatment of glomeruli with collagenase and cultivation on gelatin-coated plastic wells. Using electron microscopy and immunofluorescent staining with antibodies to intermediate filaments, factor VIII, myosin, common leucocyte antigen two cell types were identified; epithelial cells and contractile mesangial cells. Further subcultivation allowed to obtain a pure mesangial cell culture. PMID- 2110489 TI - Swelling of PHEMA based membranes in ethanol and their nitroglycerin permeabilities. AB - The aim of this study is to prepare PHEMA based polymeric membranes for a transdermal delivery system, which includes a skin permeation enhancer (i.e. ethanol) for nitroglycerin. Membranes were prepared by bulk polymerization of HEMA monomer. Polymerization was achieved in the presence of EGDMA, as the cross linker, and AIBN as the initiator. MMA was used as a comonomer to improve the mechanical properties and to adjust the permeabilities of the resulting membranes. Water was also included in the polymerization mixture to control the matrix structure. Membranes with different chemical and physical structures were prepared. Swelling behaviour of these matrices in ethanol were observed. Nitroglycerin diffusion through swollen membranes (in ethanol) were investigated. It was obtained that the relative amounts of ingredients (i.e., HEMA, MMA, EGDMA and water) in the casting solutions affect both the equilibrium swelling values and the permeabilities. By increasing the water content and by decreasing the amounts of MMA and EGDMA both parameters can be increased. AIBN does not affect these parameters significantly. PMID- 2110490 TI - The effects of stress on the development of immunological memory following low dose antigen priming in mice. AB - Observable stress effects on immune responses may be a function of the quantitative and qualitative characteristics of the stressor, and the outcome measurement of immunity. Further, the effects of stress on humoral immunity, in particular, may be sensitive to the concentrations of antigen used to elicit a response. We have studied the effects of footshock stress during the time of priming with low concentrations of antigen on the secondary response to another low dose of antigen. The secondary humoral immune response of C3H/HeJ mice to the protein antigen keyhole limpet hemocyanin was examined following footshock, exposure to the apparatus without shock, or exposure to the home cage. Footshock reproducibly depressed the IgG anti-KLH response, and the effect on the IgM response was sporadic. Initially, footshock was administered for 7 days before and 7 days after priming with low amounts of antigen. Subsequent studies demonstrated that a single footshock session delivered 24 h after priming could suppress the IgG anti-KLH response. PMID- 2110491 TI - The influence of dexamethasone on behaviorally conditioned immunomodulation and plasma corticosterone. AB - Utilizing a conditioned taste aversion paradigm we have previously shown that rats re-exposed to a saccharin solution previously paired with cyclophosphamide (CY) demonstrate significantly reduced in vitro mitogen-induced spleen cell proliferation and IgM secretion assessed 24 h after saccharin re-exposure. In this report treatment of similarly conditioned rats with dexamethasone (DEX) either before conditioning or before re-exposure abrogated the conditioned modulation of pokeweed mitogen (PWM)-induced spleen cell proliferation. The finding that DEX pretreatment on the conditioning day was as effective in abrogating the conditioned response as DEX treatment prior to the test day does not support pituitary-adrenal mediation of the conditioned immusuppressive effect following re-exposure of conditioned animals to the CS. There was no significant conditioned immunosuppression observed with respect to PHA- and Con A-induced proliferation and the influence of DEX on these parameters could not be assessed. The effect on PWM-induced IgM production was inconclusive since the reduced IgM response among conditioned animals was of only borderline significance. PMID- 2110492 TI - An analysis of personnel dose records which justifies the application of cost benefit analysis techniques in the design of an afterloading facility and the use of controlled areas and systems of work within suite to control occupational exposure. AB - The sealed source operational policies employed at the Bristol Radiotherapy and Oncology Centre were originally designed to meet the requirements of the 1972 Code of Practice by ensuring that individual personnel doses were kept below the relevant quarterly and annual dose limits. In 1982-1983, measures were taken to improve personnel radiation safety within the brachytherapy treatment facility by (a) making preparations for the introduction of Selectron medium-dose-rate (MDR) afterloading systems at the centre for intracavitary brachytherapy and (b) reviewing the operational policies to ensure that they meet the more stringent requirements of the ALARA (as low as reasonably achievable) principle, a principle subsequently embodied in the 1985 UK ionising Radiations Regulations (IRR 85). When considering the implications of making existing single-bedded side wards, originally designed for low-dose-rate brachytherapy and suitable for the new systems, the cost of the extra protection required to reduce the instantaneous dose rate in the ward corridors adjacent to the treatment room to less than 7.5 microSv h-1 had to be determined. On the basis of the cost-benefit analysis, it was decided not to provide additional shielding but rather to introduce administrative controls based on local rules which contained systems of work and the operational policies for the afterloading systems. After using the MDR afterloading systems for 2 years, a period in which there has also been a marked increase in interstitial brachytherapy, an analysis was made of the doses received by nursing staff over the past 8 years. This has shown that, in spite of higher dose rates in the corridor areas because of the use of an MDR system and the increase in interstitial techniques, the doses to ward nurses have been significantly reduced by encouraging staff to comply with the ALARA principle and the introduction of afterloading systems. PMID- 2110493 TI - Giant mid-oesophageal diverticulum: a rare cause of dysphagia. PMID- 2110494 TI - Selective alterations of high affinity [3H]forskolin binding sites in Alzheimer's disease: a quantitative autoradiographic study. AB - Quantitative autoradiographic analysis of high affinity [3H]forskolin binding sites was carried out in postmortem brains from normal controls and patients dying with Alzheimer's disease. Choline acetyltransferase (ChAT) activity and senile plaque formation were also quantified. [3H]Forskolin binding was markedly reduced in all layers of middle frontal gyrus in the Alzheimer brains and the deficit correlated with the deficit in ChAT activity in this area. In the hippocampal region [3H]forskolin binding was no different in the Alzheimer brains compared to controls, although ChAT activity was significantly reduced. There was an inconsistent reduction in [3H]forskolin binding in all layers of middle temporal gyrus which did not correlate with the cholinergic deficit. Significant senile plaque formation was observed in all 3 brain regions examined and [3H]forskolin binding did not correlate with plaque formation in any brain region. Thus, while all 3 brain regions were affected by the pathological correlates of Alzheimer's disease, [3H]forskolin binding was consistently reduced only in frontal cortex. PMID- 2110495 TI - [Use of ELISA for the detection of IgG antibodies to Mycobacterium tuberculosis in the diagnosis of tuberculosis]. AB - The presence of mycobacterial antibodies of IgG type was determined in serum, cerebrospinal fluid and pleural puncture fluid by using ELISA and soluble antigens of the strain Mycobacterium tuberculosis H37Rv. In patients suffering from tuberculosis the most frequently found titer was 1:320 and above. This titer was however found also in 30% of healthy subjects of the control group and 29% of patients with other than tuberculous disease. The sensitivity of the test was 0.7692 and its specificity 0.4594. On examining cerebrospinal fluid of patients with suspect tuberculous meningitis, positive titers of 1:640 and 1:1280 were found in two cases, while the titers of all the other patients were definitely negative. In both cases with positive titers there was also a high antibody titer in serum and additionally also culture positivity or positive biological test was evidenced. This combination of examinations allows prompt administration of antituberculous therapy in case of positivity. The results obtained in examining pleural puncture fluid and serum are open to discussion. PMID- 2110497 TI - Molecular epidemiology and novel combinations of auxotype, serovar, and plasmid content in tetracycline-resistant Neisseria gonorrhoeae isolated in Canada. AB - Between October 1987 and June 1989, 84 isolates of Neisseria gonorrhoeae carrying the TetM resistance determinant (TRNG) were received at the Laboratory Centre for Disease Control, Ottawa, from six Canadian provinces and were characterized into classes based on auxotype, serovar and plasmid content. One-fifth (17/84) of the TRNG were also penicillinase producing (PPNG). The PPNG-TRNG isolates comprised six classes based on auxotype, serovar, and plasmid content. Most (16/17) PPNG TRNG carried 3.2-MDa beta-lactamase plasmids and the 25.2-MDa TetM-containing plasmid. We report, for the first time, the association of a 4.5-MDa beta lactamase plasmid with the 25.2-MDa plasmid in a clinical TRNG isolate. Non-PPNG TRNG isolates comprised 11 classes based on auxotype, serovar, and plasmid content, including two previously unreported auxotype-serovar classes, P/IB-26 and P/IB-20. PMID- 2110496 TI - The effect of complete carcinogens on intercellular transfer of lucifer yellow in fibroblast culture. AB - The effect on permeability of gap junctions of complete powerful carcinogens, 3 methylcholanthrene (MC), 7,12-dimethylbenz(a)anthracene (DMBA), ethyl methanesulfonate (EMS), and weak carcinogens, benz(a)anthracene (BA), benzo(e)pyrene (B(e)P) as well as the aryl-hydroxylase inhibitor 7,8-benzoflavone (7,8-BF) has been studied with the use of a dye-coupling technique and transformed Djungarian hamster DM15 fibroblasts. MC, EMS and 7,8-BF were found to exert a strong inhibitory effect on cell-to-cell dye transfer. BA and DMBA had the uncoupling activity only in 2 out of 4 experiments. B(e)P was not shown to affect LY transfer between DM15 cells. The uncoupling effect of MC, 7,8-BF and EMS (only when EMS used at the concentration of 600 micrograms/ml but not 1000 micrograms/ml) appeared reversible. The causes of failure to detect DMBA and B(e)P effects on gap junctions are discussed. PMID- 2110498 TI - Breakout V. Concerns of the clinical investigator. PMID- 2110499 TI - The pelvic digit: CT correlation and review of the literature. AB - Four additional cases of the developmental anomaly known variously as pelvic "ribs" or "digits" are presented with CT correlation in three cases. Comparison is made with the 12 cases reported in the literature, and their differential diagnosis is discussed. PMID- 2110500 TI - Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment. AB - Determination of neopterin [D-erythro-6-(1',2',3'-trihydroxypropyl)pterin] in body fluids is a powerful diagnostic tool in a variety of diseases in which activation of cellular immune mechanisms is involved, such as certain malignancies, allograft rejection, and autoimmune and infectious diseases. In vitro, neopterin is released into the supernatant by peripheral blood-derived monocytes/macrophages upon stimulation with gamma-interferon. In parallel, cleavage of tryptophan by indoleamine 2,3-dioxygenase is induced. We report here that the human myelomonocytic cell line THP-1 forms neopterin and degrades tryptophan upon treatment with gamma-interferon. Like in macrophages alpha interferon and beta-interferon induce these pathways only to a much smaller degree. The action of interferons is enhanced by cotreatment with tumor necrosis factor alpha, lipopolysaccharide, or dexamethasone. gamma-Interferon-induced neopterin formation and indoleamine 2,3-dioxygenase activity are increased by raising extracellular tryptophan concentrations. The pattern of intracellularly formed pteridines upon stimulation with gamma-interferon shows the unique characteristics of human monocytes/macrophages. Neopterin, monapterin, and biopterin are produced in a 50:2:1 ratio. Thus, the THP-1 cell line provides a permanent, easily accessible in vitro system for studying the induction and mechanism of neopterin formation. PMID- 2110501 TI - Production of urothelial tumors in the heterotopic bladder of rat by benzidine derivatives. AB - Male Fischer rats which had been implanted with a heterotopic bladder were randomly divided into five groups and their heterotopic bladders were instilled once a week for 20 weeks with 0.5 ml phosphate-buffered saline:dimethyl sulfoxide solution (4:1) or this solution containing 1 mumol benzidine (BZ), N'-hydroxy-N acetylbenzidine, the N'-glucuronide of N'-hydroxy-N-acetylbenzidine, or the N glucuronide of N-hydroxy-2-aminofluorene. These bladders were then instilled once a week for an additional 30 weeks with the phosphate-buffered saline without dimethyl sulfoxide. The experiment was terminated at the end of 50 weeks. Transitional cell carcinomas were observed in 1 of 39 (control), 1 of 29 (BZ), 18 of 30 (N'-hydroxy-N-acetylbenzidine), 28 of 28 (N'-hydroxy-N-acetylbenzidine N' glucuronide), and 24 of 29 (N-hydroxy-2-aminofluorene N-glucuronide) rats. No histological alterations were observed in their natural bladders. These results demonstrate the urothelial carcinogenicity of the N-hydroxy metabolites of BZ and suggest that N'-hydroxy-N-acetylbenzidine N'-glucuronide may play a major role in the initiation of urothelial carcinogenesis by BZ in humans. PMID- 2110502 TI - Phorbol esters induce changes in adenosine deaminase, purine nucleoside phosphorylase, and terminal deoxynucleotidyl transferase messenger RNA levels in human leukemic cell lines. AB - We have studied the expression of mRNA encoding adenosine deaminase (ADA; EC 3.5.4.4), purine nucleoside phosphorylase (PNP; EC 2.4.2.1), and terminal deoxynucleotidyltransferase (TdT; EC 2.7.7.31) in different leukemic cell lines of B- and T-cell lineage. Incubation of leukemic cells in the presence of the phorbol esters, 12-O-tetradecanoyl-phorbol-13-acetate or phorbol 12,13 dibutyrate, resulted in reduction of ADA and TdT mRNA levels, while PNP mRNA levels increased under the same treatment. The effect of TPA on the activity of these enzymes correlated well with its effects on their mRNA levels. TPA caused a 40% decrease in ADA and a 60% decrease in TdT enzyme activity, after 6 h of treatment. In contrast, PNP activity increased up to 200% after 12 h of incubation with the phorbol ester. The changes induced by the phorbol esters in the levels of mRNA of ADA, PNP, and TdT, and their enzyme activities in human leukemic cell lines mimic the changes in the activities of these enzymes in developing T-lymphocytes during differentiation in vivo, suggesting a role for protein kinase C in the regulation of ADA, PNP, and TdT gene expression during lymphoid cell differentiation. PMID- 2110503 TI - Distribution of covalent DNA adducts in mouse epidermal subpopulations after topical application of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene. AB - The distribution of benzo(a)pyrene [B(a)P] and 7,12-dimethylbenz(a)anthracene (DMBA):DNA adducts was examined in five different subpopulations of SENCAR mouse epidermal cells separated based on buoyant density in continuous gradients of 61.5% Percoll. Three fractions consisted of primarily basal cells (Fractions 3 to 5), while two less dense fractions (Fractions 1 and 2) consisted of primarily differentiating keratinocytes. The levels of B(a)P and DMBA:DNA adducts were examined at 1 h, 6 h, 24 h, 72 h (except DMBA), and 28 days after a single topical application of an initiating dose. Among the basal cell subpopulations, the level of covalent B(a)P:DNA adducts in Fraction 5 cells was significantly higher (P less than 0.05) than Fractions 3 and 4 at every time point examined. On the other hand, B(a)P:DNA adduct levels in Fraction 5 were only significantly higher than Fraction 2 at 6 h and 72 h and not significantly different from Fraction 1 at any time point. With DMBA, no significant differences were initially observed in the levels of covalent DNA adducts among the various Percoll fractions at 1 h and 6 h after treatment. However, at 24 h and at 28 days. Fraction 5 cells had significantly higher (P less than 0.05) levels of covalent DMBA:DNA adducts than Fractions 1 to 4. To explore whether the observed differences in DNA adduct levels were due to differences in metabolic activation, we examined the levels of covalent adducts among epidermal subpopulations after topical application of (+/-)-anti-benzo(a)pyrene-7,8-diol-9,10-epoxide (anti BPDE). Interestingly, 3 h after treatment with anti-BPDE, significantly higher (P less than 0.05) levels of binding were found in Fraction 5 compared with Fractions 1 to 4. High-pressure liquid chromatographic analyses of B(a)P and DMBA:DNA adducts 6 h and 24 h after treatment did not show any significant differences in adduct profiles among the various subpopulations. These results demonstrate the presence and persistence of hydrocarbon:DNA adducts in all epidermal subpopulations isolated on continuous Percoll gradients for at least 28 days after treatment. Furthermore, of the three basal cell subpopulations, the most dense cells (Fraction 5) developed the highest DNA adduct levels within 24 h and retained these higher levels over 28 days. Finally, differences in DNA adduct levels among epidermal subpopulations do not appear to result from different metabolic capabilities of the cells. The potential significance of these results is discussed in terms of the process of skin tumor initiation. PMID- 2110504 TI - An abnormal profile of DNA replication intermediates in Bloom's syndrome. AB - Bloom's syndrome (BS) cells display a characteristic genomic instability, notably an elevated frequency of sister-chromatid exchange. Replicating DNA in cultured BS cells was labeled with [3H]thymidine using several time schedules. Separation of DNA in agarose gels showed high molecular weight DNA and three classes of DNA replication intermediates: 20-kilobase DNA, 10-kilobase DNA, and Okazaki fragments. In contrast newly replicated DNA from normal cells showed no 20 kilobase DNA replication intermediates. Certain BS cells, exceptional in that their characteristic genomic instability has for unknown reasons been corrected, also differed from normal cells in having the 20-kilobase intermediate, but they differed from both normal cells and the other (the uncorrected) BS cells in lacking the 10-kilobase DNA replication intermediates. PMID- 2110505 TI - Molecular neuropathology of Alzheimer's disease: in situ hybridization studies. AB - 1. Abundant senile plaques and neurofibrillary tangles in certain brain regions constitute the major neuropathological characteristics of Alzheimer's disease. Recent work has established that the amyloid beta protein, which is derived from a large precursor, constitutes the major constituent of plaque amyloid, whereas the microtubule-associated protein tau is a component of the paired helical filament, the major constituent of neurofibrillary tangles. 2. Multiple isoforms of amyloid beta protein precursor and tau protein are produced from a single gene through alternative RNA splicing. By Northern blotting amyloid beta protein precursor transcripts are found throughout central and peripheral tissues, whereas tau protein transcripts are only found in the nervous system. 3. In the central nervous system the cellular localization of amyloid beta protein precursor and tau protein transcripts is neuronal. The cells affected in Alzheimer's disease patients produce both types of transcripts; however, the various transcripts are also found in cells not affected in the course of the disease. At present, there exists no evidence to suggest that an overproduction of amyloid beta protein precursor or tau protein is the reason for plaque and tangle formation. The formation of the latter probably results from posttranslational events. PMID- 2110506 TI - Dominantly inherited expression of BID, an invariant undiversified T cell receptor delta chain. AB - In BALB/c lung and lymph node gamma delta T cells, a large fraction of the expressed V delta 5 genes consist of an invariant sequence, BID (for BALB/c invariant delta). BID results from a direct joining of the V delta 5, D delta 2, and J delta 1 segments, which conserve their complete germline coding sequences. In C57BL/6 (H-2b) mice, where identical and functional segments are present in the germline, BID is absent. It appears that BID+ gamma delta T cells are positively selected by factors encoded outside of the classical MHC region, as indicated by their dominance in F1(C57BL/6 x BALB/c) and in BALB.B (H-2b) mice. Additional observations, including the expression of BID in BALB/c nu/nu but not in C57BL/6 nu/nu mice, suggest that the expansion of BID+ T cells essentially occurs extrathymically. PMID- 2110507 TI - Extinction of an immunoglobulin kappa promoter in cell hybrids is mediated by the octamer motif and correlates with suppression of Oct-2 expression. AB - When immunoglobulin-expressing B cells are fused with fibroblasts, immunoglobulin expression is rapidly and selectively suppressed. here we demonstrate that the conserved octamer motif of a kappa light chain gene promoter plays a crucial role in mediating this "extinction" phenomenon. Replacement of this octamer site by an Sp1 or NF1 binding site is sufficient to bypass extinction. Furthermore, in early cell hybrids, immunoglobulin suppression is correlated with absence of the cell specific transcription factor Oct-2 and its transcripts. Such hybrids cannot support transcription of a transiently introduced reporter plasmid, driven by an octamer-containing promoter, unless an expression vector encoding Oct-2 is cotransfected. Transfection of the same Oct-2 expression vector into hybrid cells is also sufficient to "reactivate" an integrated kappa promoter construct. Thus, our data further establish the role of Oct-2 for immunoglobulin transcription and show that in B cell x fibroblast hybrids, the lack of a necessary cell-specific transcription factor is involved in the extinction of immunoglobulin expression. PMID- 2110508 TI - Demonstration in living cells of an intragenic negative regulatory element within the rodent c-fos gene. AB - We studied c-fos gene expression in rat fibroblasts by microinjection of regulatory DNA sequences, such as the serum response element (SRE) present in c fos promotor, in order to compete directly with such sequences for binding of putative regulatory factors. We show that an additional fos intragenic regulatory element (FIRE) is located at the end of exon 1. When coinjected with an SRE oligonucleotide, it induced c-fos expression in quiescent cells, whereas injection of SRE sequence alone failed to do so. Moreover, injection in quiescent cells of an SRE oligonucleotide together with a p-fos-lacZ construct containing the c-fos SRE as well as an in-frame insertion of FIRE resulted in a block to beta-galactosidase expression that can be relieved by coinjection of the FIRE sequence. PMID- 2110509 TI - Chloroquine's modulation of endothelial cell activity induced with basic fibroblast growth factor and human serum: effect on mitogenesis, protease production and cell migration. AB - Chloroquine modulates the activity of cultured human microvascular endothelial (HOME) cells in a complex fashion. At concentrations of 5-25 microM, CQ inhibits basic fibroblast growth factor (bFGF-) and human serum-induced mitogenic activity in these cells, in a dose-dependent manner. The kinetics of CQ's inhibitory actions on serum-induced mitogenesis in HOME cells slowly develops with only 30% of maximum inhibition reached after 24 hours. In HOME cells grown in serum-free medium, CQ raised tissue-plasminogen activator antigen levels in cell extracts. There was also a potentiation of bFGF-induced t-PA production. The kinetics of CQ's stimulatory effect on t-PA production by HOME cells, suggest that this effect precedes its inhibitory actions on mitogenesis. This effect of CQ on t-PA generation in endothelial cells was susceptible to cycloheximide inhibition. In wound assays, HOME cell migration, induced with bFGF and HS, was potentiated by CQ. PMID- 2110510 TI - Probable enteric non-A, non-B hepatitis in a returned traveller--Alberta. PMID- 2110511 TI - Effects of dietary perilla oil, soybean oil and safflower oil on 7,12 dimethylbenz[a]anthracene (DMBA) and 1,2-dimethyl-hydrazine (DMH)-induced mammary gland and colon carcinogenesis in female SD rats. AB - The effects of diet supplemented with perilla oil, which contains a large amount of n-3 alpha-linolenic acid, and n-6 linoleic acid rich soybean and safflower oil supplemented diets on 7,12-dimethylbenz[a]anthracene (DMBA)- and 1,2 dimethylhydrazine (DMH)-induced mammary gland and colon carcinogenesis were investigated in female SD rats. Groups of 23 or 24, 5 week old animals were first given three s.c. injections of 40 mg/kg body wt DMH followed by a single intragastric administration of 50 mg/kg body wt DMBA within 2 weeks of the commencement. Starting 1 week after the DMBA treatment, they were administered pellet diet containing 10% perilla oil, soybean oil or safflower oil for the succeeding 33 weeks. Histological examination revealed that the resultant numbers of mammary tumors per rat were significantly lower in rats given perilla oil diet (4.4 +/- 2.5) than in the soybean oil diet group (6.5 +/- 3.9). Furthermore, colon tumor incidence was significantly lower in animals receiving the perilla oil supplement (18.2%) than in those given safflower oil diet (47.4%), and the numbers of colon tumors per rat tended to be lowest in rats administered perilla oil. Also the incidence of nephroblastomas in rats receiving perilla oil diet (0%) was significantly lower than that for the soybean oil diet group (23.8%). The results thus indicate that the alpha-linolenic acid (n-3)-rich perilla oil diet inhibits development of mammary gland, colon and kidney tumors as compared to linoleic acid (n-6)-rich safflower or soybean oil diet. PMID- 2110513 TI - Induction of specific frameshift and base substitution events by benzo[a]pyrene diol epoxide in excision-repair-deficient Escherichia coli. AB - We have determined the DNA alterations recovered after treatment with (+-)-r-7,t 8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+-)-anti-BPDE] in the lacI gene of excision-repair-deficient (Uvr-) Escherichia coli. The high induction of -(G:C) frameshifts, G:C----T:A and A:T----T:A transversions, and the presence of complex mutations of a particular motif, distinguish the mutational distribution recovered in the Uvr- strain, although other mutational classes, including -(A:T) frameshifts and duplications, were also moderately induced. The great majority of -(G:C) frameshifts, the predominant mutation recovered, occurred in runs of G residues. The G:C----T:A transversion was found to occur more frequently (10/12 occurrences) at 5'-Y-G-3' sites, sequences at which the labile BPDE:N7G adduct has been predicted to occur. Moreover, the relative proportions of G:C----T:A, A:T----T:A and G:C----A:T mutations correlate well with the expected proportions of alkali-labile lesions at G, A and C residues. These results support the model that (+-)-anti-BPDE-induced base substitution mutagenesis in E.coli proceeds through abasic intermediates across from which adenine is preferentially incorporated during replication. PMID- 2110512 TI - Anti-tumor promoting action of phthalic acid mono-n-butyl ester cupric salt, a biomimetic superoxide dismutase. AB - Skin tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by a concurrent and topical application of phthalic acid mono-n-butyl ester cupric salt (PAMBCu) in CD-1 mice initiated with 7,12 dimethylbenz[a]anthracene. PAMBCu inhibited TPA-caused epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. skin inflammation. However, neither PAMBCu nor superoxide dismutase (SOD) inhibited TPA-caused ODC induction in primary cultured mouse epidermal cells. 7 Bromomethylbenz[a]anthracene (BrMBA) is known to be a non-TPA type of tumor promoting agent. Epidermal ODC induction and inflammation caused by BrMBA were not inhibited by a concurrent application of PAMBCu. When mice were topically treated twice with PAMBCu, i.e. concurrently with and 7 h after BrMBA treatment, BrMBA-caused ODC induction was markedly suppressed. The same dose regimen of PAMBCu, however, failed to inhibit tumor promotion and inflammation caused by BrMBA. PAMBCu showed SOD-mimetic activity in superoxide generating systems, i.e. xanthine-xanthine oxidase reaction and TPA-stimulated polymorphonuclear leukocytes (PMN). Mono-n-butyl phthalate, which lacks SOD-mimetic activity, failed to inhibit TPA-caused ODC induction and skin inflammation. Therefore, inhibition by PAMBCu of TPA-caused tumor promotion, epidermal ODC induction and inflammation may be attributable to its SOD-mimetic activity. The results also support the contention that a superoxide anion of non-epidermal cell origin, such as PMN and macrophages, plays a role (probably some enhancing role) in in vivo ODC induction and tumor promotion caused by TPA. Failure of PAMBCu to inhibit BrMBA-caused tumor promotion suggests that superoxide anion generation is not involved in the tumor promoting action of this agent and that the anti-tumor promoting action of PAMBCu is dependent on the nature of the tumor promoting agents. PMID- 2110514 TI - Biotransformation of aflatoxin B1 in rabbit lung and liver microsomes. AB - Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin that requires bioactivation to AFB1-2,3-oxide for activity. In addition to epoxidation, microsomal monooxygenases biotransform AFB1 to the less toxic metabolites, aflatoxin M1 (AFM1) and aflatoxin Q1 (AFQ1). The lung is at risk from AFB1 both via inhalation and via the circulation. In the present study, we have characterized rabbit lung and liver microsomal AFB1-DNA binding (an index of AFB1-2,3-oxide formation), AFM1 formation and AFQ1 formation. Vmax values for AFB1-DNA binding were not different between lung and liver when expressed per mg microsomal protein (1.06 +/- 0.13 and 2.12 +/- 1.30 nmol/mg/h for lung and liver respectively), but lung values were greater than liver when expressed per nmol cytochrome P450 (3.64 +/- 0.31 and 1.29 +/- 0.70 nmol/nmol P450/h for lung and liver respectively). Km values for this reaction were not different between lung and liver. Vmax values for AFM1 formation in liver microsomes were greater than in lung when expressed per mg protein, but not when expressed per nmol P450. No differences were detected for the Km for AFM1 formation between lung and liver microsomes. For AFQ1 formation, no differences were detected between Vmax values of lung and liver, regardless of whether results were expressed per mg protein or per nmol P450, while the Km for AFQ1 formation was lower in liver. SKF-525A inhibited these reactions by 63-74% in lung microsomes and 90-96% in liver microsomes. These results indicate that the lung is capable of activating AFB1, and that rabbit lung microsomes contain high activity for this reaction. Furthermore, little AFM1 and AFQ1 are formed in lung microsomes, leading to minimal shunting of AFB1 from the activation pathway. PMID- 2110515 TI - Quantification of [Ca2+]i in perfused hearts. Critical evaluation of the 5F-BAPTA and nuclear magnetic resonance method as applied to the study of ischemia and reperfusion. AB - Calcium has been implicated as a mediator of cell injury in ischemia and reperfusion, but direct measurements of Ca2+ are required to refine this idea. We used nuclear magnetic resonance spectroscopy and the Ca2+ indicator 5F-BAPTA to measure [Ca2+]i in perfused ferret hearts. Several lines of evidence are presented to show that loading with the acetoxymethyl ester of 5F-BAPTA is not significantly complicated by accumulation of partially de-esterified metabolites, compartmentalization into mitochondria, or disproportionate uptake into endothelial cells. During 20 minutes of total global ischemia at 30 degrees C, time-averaged [Ca2+]i increased significantly, reaching peak values roughly three times control at 15-20 minutes. Reperfusion resulted in a persistent elevation of [Ca2+]i during the first 5 minutes, but not afterward. Although the nonlinear response of 5F-BAPTA to [Ca2+] leads to underestimation of the true time-averaged [Ca2+]i, the measured alterations of intracellular Ca2+ homeostasis during ischemia are large compared with the likely errors in quantification. Phosphorus nuclear magnetic resonance spectroscopy of 5F-BAPTA-loaded hearts reveals changes during ischemia similar to those recorded previously in hearts not containing a Ca2+ indicator. Developed pressure recovers to only 50% of control values during reflow, indicating that the presence of 5F-BAPTA in the cytosol does not protect against stunning, at least when the extracellular calcium concentration has been raised to 8 mM. We conclude that 5F-BAPTA provides useful measurements that reveal that time-averaged [Ca2+]i rises during ischemia and returns to control levels soon after reperfusion. PMID- 2110516 TI - Whistling epilepsy: a case report. AB - Whistling, as an ictal symptom, has been previously reported in frontal lobe epilepsy. For the first time in the literature, we present a patient with complex partial seizures of the temporal region associated with this peculiar symptom. PMID- 2110517 TI - Reflex petit mal absence? AB - The importance of tactile somatosensory stimuli as a triggering mechanism in provoking epileptic seizures is widely acknowledged. These seizures are mostly partial ones with secondary generalization, but may also be, rarely, primary generalized seizures. Up to now, no case of petit mal absence, triggered by somatosensory stimuli, has been described. The subject of this report is a 15 month-old girl, who for a period of 3 months presented absence induced by finger tapping on her forehead or in the parietal region; the duration of the attacks ranged from 6 to 12 seconds. The EEG showed a characteristic pattern of diffuse discharges of 3 Hz/sec spike and wave complexes. During this critical period, the child was well, except for the seizures. Possible mechanisms for triggering this type of seizure are discussed. PMID- 2110518 TI - Resource productivity and returns to scale in school-based mouthrinsing programs. AB - The viability of community dental programs is influenced by various factors, including costs and effectiveness. Costs, in turn, are influenced by the prices and productivity of resources, and variations in these will influence not only comparisons among programs providing a homogeneous service but also any conclusions that can be drawn about cost-effectiveness. This paper eliminates wage effects and examines resource productivity and returns to scale in relationship to the size of a group of school-based mouthrinsing programs. The research questions were to determine: 1) whether the programs exhibit increasing, decreasing, or constant returns to scale, and 2) the productivity of labor and capital. Data from 14 programs in the US were pooled for 2 yr to yield 28 observations. The production relationship between output (numbers of participants) and inputs (labor and capital) was specified in a Cobb-Douglas model. Findings were that 1) the programs exhibited decreasing returns to scale (P less than 0.01); and 2) the average and marginal productivities of labor and capital declined (P less than 0.001). The implications of these findings are that, with equal wages and homogeneous labor, the average cost of mouthrinsing per participant would have increased as a function of the size of these programs. To the extent that the economics of community dental programs are influenced not only by the costs and productivity of the resources they use but also by their size, there may be some value in research on the economics of optimum program size and the role of management in program organization. PMID- 2110519 TI - Evaluation of a routine for prevention and treatment of fissure caries in permanent first molars. AB - Fissure sealing as well as fluoride varnish have shown good preventive effect against fissure caries in newly erupted teeth. The purpose of this study was to evaluate a clinical routine in which these two methods were combined. The evaluation was done in a public dental clinic in Norway, and three dentists performed and evaluated the treatment. The population belonged to two different year classes (born 1978 and 1979), 196 in all, and they were followed semiannually from age 6 until 8 and 9 yr, respectively. The routine was as follows: all erupted permanent first molars without fissure caries were cleaned and painted with a fluoride varnish (Duraphat) every 6 months. Fissures showing incipient caries were opened with a rotating instrument and sealed if caries was restricted to the enamel. Amalgam fillings were placed if caries had progressed to the dentin. The operator time required for the fissure treatment was recorded. After 2 yr observation of children born in 1978 and 1979, 72% of the fissures were intact, 13% had been sealed, and 15% filled, and the corresponding figures after 3 yr (1978-children) were 65%, 15%, and 20%. In approximately 45% of the children all four permanent molars were intact, while about 12% had all molars sealed or filled. The average time spent for application of sealants was 4.1 min and for application of amalgam fillings 5.9 min. PMID- 2110520 TI - Valproate: an update--the challenge of modern pediatric seizure management. PMID- 2110521 TI - [Observed genetic effects in Drosophila after exposure to weightlessness]. PMID- 2110522 TI - [Microbial transformation of polychlorinated biphenyls in in polar marine regions]. PMID- 2110523 TI - Ganglioside GM1 elevation in DBA/2 mouse embryos. AB - The composition of whole embryo gangliosides at embryonic day E-12 was compared among the C57BL/6 (B6) DBA/2 (D2), and C3H mouse strains. N-acetylneuraminic acid was the predominant sialic acid species in the E-12 embryos. N-glycolyneuraminic acid was either undetectable or present in only trace amounts. Whole embryo ganglioside sialic concentration was significantly lower in D2 embryos than in B6 or C3H embryos. GM3 and GD3 were the most abundant ganglioside species in each strain and comprised approximately 75% of the total distribution. The D2 embryos expressed an elevation of GD1a and a reduction of GQ1b relative to B6 and C3H. Also, the level of GM1 was significantly higher in the D2 embryos than in the B6 or C3H embryos. Since a reduction of beta-galactosidase activity and an elevation of GM1 concentration in brain were previously reported in postnatal DBA mice, our results suggest that the elevated GM1 in D2 embryos may result from a reduced activity of GM1 beta-galactosidase. PMID- 2110524 TI - Septicemia after endoscopic retrograde cholangiopancreatography. AB - Clinical and bacteriological data from 55 patients who developed septicemia within 3 days after ERCP were collected. Forty-four patients presented with septicemia after therapeutic endoscopy, with incomplete drainage in forty, eight after diagnostic ERCP performed in obstructed bile ducts in another center and not followed by endoscopic therapy, and three with a normal common bile duct after diagnostic ERCP. The incidence of septicemia is significantly higher in cases of malignant obstruction than in benign obstruction (21% vs 3%; p less than 0.01), due mainly to the problems of drainage associated with tumoral infiltration. Forty-eight patients (87%) had incomplete bile duct drainage when they developed septicemia, and among the seven remaining cases, 3 had cholecystitis and 3 abscesses in the biliopancreatic area. Previous diagnostic ERCP without drainage was also clearly associated with septicemia after therapeutic ERCP. The most commonly isolated bacteria from blood and bile cultures were Pseudomonas aeruginosa and Escherichia coli. P. aeruginosa was observed mainly in patients referred from other centers after previous diagnostic ERCP, and was unusual in patients without previous ERCP. It is associated with problems in the disinfection of the scopes. Six deaths were attributed to sepsis, always in patients with incomplete biliary drainage which could not be improved. In most of the cases, septicemia after ERCP is related to incomplete bile duct drainage, and in some cases, to biliopancreatic infected collections. Careful disinfection of the endoscopes and other endoscopic devices is mandatory to avoid an unacceptably high rate of P. aeruginosa infection. PMID- 2110525 TI - Phenotyping of lymphocytes following transplantation of allogeneic rat pancreatic islets into streptozotocin-diabetic recipients. AB - We investigated the phenotypes of peripheral and cervical lymphocytes in allografted pancreatic islet recipients during graft rejection. Grafting 2000 pancreatic islets, obtained from LEW.1A rats, into streptozotocin-diabetic non immunosuppressed LEW.1W rats acute rejection occurred within 7.0 +/- 0.6 days. Neither the T-cells (W3/13+), nor the T helper (W3/25+) or T-suppressor (OX-8+) lymphocytes were markedly altered during rejection crisis in peripheral or cervical lymphocytes. When using monoclonal antibodies detecting activation markers (OX-17 for class II antigens; ART-18 for interleukin-2 receptor) a significant increase of OX-17+ cells and OX-17+ T-lymphocytes could be observed in lymph node lymphocytes from 24 h after transplantation until 7 days, whereas the peripheral lymphocytes behaved inconspicuously. The results underline the uselessness of peripheral lymphocytes to monitor allogeneic destruction of minimal amounts of grafted tissue by using presently known differentiation and activation markers of lymphocytes. PMID- 2110526 TI - Cell cycle-dependent DHFR and t-PA production in cotransfected, MTX-amplified CHO cells revealed by dual-laser flow cytometry. AB - The cell cycle-dependent regulation of the cellular dihydrofolate reductase content (DHFR) and tissue plasminogen activator (t-PA) production and secretion in plasmid-amplified cells was investigated in the DHFR-negative CHO cells transfected with the plasmid pSV-tPA.dhfr. This plasmid, carrying the dhfr and t PA gene under control of different promotors, was amplified by serial passages in 5 microM methotrexate (MTX) for dhfr gene amplification. The intracellular amount of DHFR was quantitated in viable cells by MTX-FITC labeling and flow cytometric analysis of the FITC fluorescence. In comparison with the original CHO cells, the pSVtPA.dhfr-amplified cells showed a greater than 230-fold increase in MTX-FITC fluorescence. Using dual laser flow cytometry (uv: vital cell cycle with Hoechst 33342; 488 nm: DHFR with MTX-FITC), we show a maximum increase in the intracellular DHFR content during G1 and/or at G1/S transition (100 to 157%), followed by a continuous increase to 200% during S and G2/M. To determine t-PA production CHO cells were sorted from G1-, early/late S-, and G2/M-phase. After 1 , 2-, and 4-h incubation periods, t-PA production was quantitated using a sensitive t-PA ELISA technique. We found that t-PA production and secretion (2-h assay), unlike the expression of DHFR, increased continuously from relatively 100% in G1 to 127% in early S and reached its maximum of 159% in late S, whereas in G2/M-phase it decreased to 118%. Our results show that in pSVtPA.dhfr coamplified CHO cells gene products DHFR and t-PA both exhibit different cell cycle-correlated accumulation and secretion, respectively, indicating that the brightest MTX-FITC-positive cells (G2/M) do not display the highest t-PA secretion rate. PMID- 2110527 TI - Cultivation of mammalian cells in heat-sealable pouches that are permeable to carbon dioxide. AB - Petri plates, 96-well plates, and other unsealed culture vessels are the chief cause of air-borne contamination of cell cultures. In this study, heat-sealable plastic pouches that are permeable to CO2 and other gases are used as a means to avoid contamination. Several applications of heat-sealable pouches are described. First, petri plates can simply be sealed in a wide variety of plastic films that are permeable to CO2. Second, a few CO2-permeable plastic films can be used directly as substrata for mammalian cell growth and can also be cut with a simple hole punch for the isolation of clones. Third, one can grow cells in chemically sterilized carbonic acid solutions and thereby avoid the use of a CO2 incubator entirely. PMID- 2110528 TI - The blood-brain barrier protects foreign antigens in the brain from immune attack. AB - To examine the role of the blood-brain barrier (BBB) in maintaining immune privilege in the brain, the BBB in the region of stably integrated mouse neural grafts implanted in neonatal rat brains was transiently disrupted by intracarotid infusion of hypertonic mannitol. This led to graft rejection and to prominent expression of major histocompatibility complex (MHC) antigens on cells adjacent to the graft. Grafts in control animals receiving an intracarotid infusion of isotonic saline showed only rare MHC expression and no increased incidence of rejection. Opening the barrier in the absence of a graft caused neither MHC expression nor cellular infiltration within the brain, suggesting that the effects of the hypertonic infusion were not produced by an indirect injury mediated effect on the host brain. We conclude that the integrity of the blood brain barrier is an important factor in the relative immune privilege of nonsyngeneic neural grafts. PMID- 2110529 TI - Alterations in prealbumin concentration after adrenal autotransplantation for Parkinson's disease. AB - The cerebrospinal fluid of eight patients with Parkinson's disease who underwent adrenal medullary autotransplantation was analyzed using SDS-polyacrylamide gel electrophoresis. A protein, subsequently identified as prealbumin, was noted to change in concentration over the intraoperative to 18-month postoperative time course. The qualitative changes observed on visual inspection were confirmed and quantified using laser densitometry. The concentration of prealbumin increased by an average of 90% when the intraoperative and 12-month samples were compared. This increase persisted at 18 months. The ratio of prealbumin to albumin also increased from intraoperative to 12 months by an average of 56%. This suggests that the increases in PA are the result of choroid plexus activation rather than a nonspecific breakdown of the blood-brain barrier. Given the association of prealbumin with other nervous system diseases, as well as its known ability to bind multiple substances, these findings may have important implications. Alterations in prealbumin may be responsible for the improvement seen in some patients who receive adrenal medullary autotransplants. Alternatively, prealbumin may be implicated in the pathophysiology of Parkinson's disease. PMID- 2110530 TI - Sequence-specific [1H]NMR resonance assignments and secondary structure identification for 1- and 2-zinc finger constructs from SW15. A hydrophobic core involving four invariant residues. AB - Complete [1H]NMR resonance assignments are presented for the second of the three zinc fingers from SW15 as it appears in both 1- and 2-finger constructs. Signals from finger 2 are unaffected by the presence or absence of finger 1, showing that the protein has a modular construction. The structure of finger 2 comprises a helix running from N56 to Q67, and a region approximating to an anti-parallel beta-sheet running from Y42 to F53. These features combine to produce a hydrophobic core in the structure involving the invariant residues Y42, F53, L59 and H62. PMID- 2110531 TI - Acyl coenzyme A: 6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum and Aspergillus nidulans. AB - A study of the final stages of the biosynthesis of the penicillins in Penicillium chrysogenum has revealed two types of enzyme. One hydrolyses phenoxymethyl penicillin to 6-aminopenicillanic acid (6-APA). The other, also obtained from Aspergillus nidulans, transfers a phenylacetyl group from phenylacetyl CoA to 6 APA. The acyltransferase, purified to apparent homogeneity, had a molecular mass of 40 kDa. It also catalyses the conversion of isopenicillin N (IPN) to benzylpenicillin (Pen G) and hydrolyses IPN to 6-APA. In the presence of SDS it dissociates, with loss of activity, into fragments of ca 30 and 10.5 kDa, but activity is regained when these fragments recombine in the absence of SDS. PMID- 2110532 TI - Interaction of small G proteins with photoexcited rhodopsin. AB - Bovine rod outer segment (ROS) membranes contain in addition to the heterotrimeric G protein transducin, several small GTP-binding proteins (23-27 kDa). Furthermore, these membranes contain two substrate proteins (about 22 and 24 kDa) for botulinum C3 ADP-ribosyltransferase known to ADP-ribosylate small G proteins in any mammalian cell type studied so far. Most interestingly, [32P]ADP ribosylation of ROS membrane small G proteins by C3 is regulated by light and guanine nucleotides in a manner similar to pertussis toxin-catalyzed [32P]ADP ribosylation of the alpha-subunit of transducin. These findings suggest that not only the heterotrimeric G protein transducin but also the C3 substrate small G proteins present in ROS membranes interact with photoexcited rhodopsin and thus contribute to its signalling action. PMID- 2110533 TI - A rev/beta-galactosidase fusion protein binds in vitro transcripts spanning the rev-responsive element of human immunodeficiency virus type 1 (HIV-1). AB - The rev protein of human immunodeficiency virus type 1 (HIV-1), a phosphoprotein of 20 kDa apparent molecular mass, is essential to target the mRNA for virion polypeptides into the cytoplasm. This effect is mediated by a specific RNA stretch (rev-responsive element = RRE) localized within a 3'-terminal segment of the mRNA encoding virion proteins. We present evidence that rev expressed as a beta-galactosidase fusion protein in E. coli forms a complex with in vitro transcripts containing the RRE; it can be precipitated by monoclonal antibodies with rev or beta-galactosidase specificity. In addition, specific binding of rev protein to RNA could be demonstrated by Northwestern blotting. PMID- 2110534 TI - A high ratio of chromogranin A to synaptin/synaptophysin is a common feature of brains in Alzheimer and Pick disease. AB - Chromogranin A and synaptin/synaptophysin were characterized by immunological methods in human autopsy brain tissue from patients with Alzheimer's and Pick's disease. In immunoblots there was no qualitative difference between the antigens in control and diseased brain, but significant quantitative differences were found. In all Alzheimer cases there was a significantly lower level of synaptin/synaptophysin, whereas chromogranin A was higher in 4 out of 5 cases and in all cases relative to synaptin/synaptophysin. An analogous finding was obtained for Pick's disease. Immunohistologically a consistent staining of neuritic plaques for chromogranin A, but not for secretogranin II was found in Alzheimer cases. In Pick's disease the characteristic Pick bodies showed an analogous specific immunostaining. PMID- 2110535 TI - Characterization of four G0-type proteins purified from bovine brain membranes. AB - Recently we reported there were at least four types of G0 or G0-like proteins in bovine brain membranes based on their elution profiles from Mono Q columns and their immunological reactivities; one of the proteins was purified as an alpha monomeric form, and the others as alpha beta gamma-trimers. The four proteins, of which alpha-subunits were confirmed to be a family of G0-type by an immunoblot analysis, were thus referred to as alpha (0)1, G(0)2, G(0)3 and G(0)4, respectively, in order of their elutions from the column. Immunostained peptide mappings arising from proteolytic digestions of the four alpha-subunits, together with their fragmentation patterns containing radiolabeled ADP-ribose that had been incorporated by pertussis toxin-catalyzed ADP-ribosylation, suggested that the four G0-alpha were classified into either of two groups such as alpha (0)1 and G(0)2-alpha, or G(0)3-alpha and G(0)4-alpha. The kinetic parameters of their GTPase activities, however, revealed that there were different properties between alpha (0)1 and G(0)2-alpha or G(0)3-alpha and G(0)4-alpha. Thus, the four G0-type proteins appeared to be different entities from one another. PMID- 2110536 TI - Botulinum ADP-ribosyltransferase activity as affected by detergents and phospholipids. AB - GTP-binding proteins with Mr values of 22,000 and 25,000 in bovine brain cytosol were ADP-ribosylated by an exoenzyme (termed C3) purified from Clostridium botulinum type C. The rate of C3-catalyzed ADP-ribosylation of the partially purified substrates was extremely low by itself, but was increased enormously when a protein factor(s) obtained from the cytosol was simultaneously added. The rate of the C3-catalyzed reaction was also stimulated by the addition of certain types of detergents or phospholipids even in the absence of the protein factors. The ADP-ribosylation appeared to be enhanced to an extent more than the additive effect of either the protein factors or the detergents (and phospholipids). Thus, ADP-ribosylation catalyzed by botulinum C3 enzyme was affected not only by cytoplasmic protein factors but also by detergents or phospholipids in manners different from each other. PMID- 2110537 TI - Double-blind, placebo-controlled multicentre trial of the efficacy and tolerance of morniflumate suppositories in the treatment of tonsillitis in children. AB - The efficacy and tolerability of morniflumate suppositories used together with phenoxymethylpenicillin were studied in a placebo-controlled, double-blind trial in 101 children with acute tonsillitis. Patients received a suppository containing 400 mg morniflumate or placebo twice daily for 4 days; all patients also received 1,500,000 IU/day phenoxymethylpenicillin. Response to treatment was assessed by clinical examination before and after 2 and 4 days' treatment. Efficacy was evaluated by resolution of oropharyngeal pain, congestion, fever, size and sensitivity of adenopathies, quality of life and duration of sleep. Body temperature fell rapidly after the start of treatment. There was also resolution of pharyngeal pain, earache, dysphagia and adenopathy. Spontaneous pharyngeal pain was present after 4 days in significantly (P = 0.03) fewer patients receiving morniflumate than receiving placebo. It is suggested that morniflumate combined with antibiotic therapy is an effective and well-tolerated treatment for tonsillitis in children. PMID- 2110538 TI - Antibody production in vitamin A-depleted rats is impaired after immunization with bacterial polysaccharide or protein antigens. AB - Vitamin A nutritional status has been implicated as important in maintaining the integrity of immune functions. We have determined the effect of vitamin A (retinol) depletion on the ability of young animals to produce antibodies after challenge with various bacterial antigens. Male Lewis rats raised on vitamin A free or adequate diets were immunized either near 40 days of age, before signs of vitamin A deficiency were apparent, or near 47 days of age when symptoms of deficiency were beginning to be manifest. For rats immunized with polysaccharide antigens from Streptococcus pneumoniae or Neisseria meningitidis, antibody production did not exceed 0-19% of the response of control rats. Vitamin A depletion also severely compromised the response to two T cell-dependent antigens, tetanus toxoid and sheep red blood cells. In striking contrast, retinol depleted rats immunized with lipopolysaccharides from Pseudomonas aeruginosa and Serratia marcesens produced an antibody response indistinguishable from retinol sufficient animals. These lipopolysaccharides could elicit antibodies in rat pups, whereas the capsular polysaccharide antigens could not. This is consistent with the characteristics of type 1 and type 2 antigens, respectively. These studies indicate that retinol status is an important determinant of the humoral immune response to certain types of antigen and suggest that antibody production to capsular polysaccharides and T cell-dependent antigens is particularly dependent on adequate retinol status. PMID- 2110539 TI - Enzymatically activated microencapsulated liposomes can provide pulsatile drug release. AB - A system for the delayed or pulsed release of biologically active substances was achieved by encapsulating liposomes containing the substance of interest inside microcapsules. The microcapsules retain the liposomes but allow controlled diffusion of the active substance when it is released from the liposomes. Furthermore, by coating the liposomes with phospholipase A2 (an enzyme that removes an acyl group from the 2 position of phospholipids) before placing them within the microcapsule, a pulsatile release pattern was achieved both in vitro and in vivo. The time of onset of the pulse as well as the release rate can be controlled by the amount of phospholipase A2, the molecular weight of the poly(L lysine) that is used to coat the microencapsulated liposomes, and the composition of the phospholipid bilayer membrane. Even at 37 degrees C the system would protect a model enzyme (horseradish peroxidase). When not placed inside the microencapsulated liposomes, the enzyme lost its activity in solution at 37 degrees C in a few days, whereas it retained 40% of the initial activity after 30 days of incubation at 37 degrees C inside the microencapsulated liposomes. PMID- 2110540 TI - Forceful balloon dilation: an outpatient procedure for achalasia. AB - The initial treatment of choice in patients with achalasia is balloon dilation. Heretofore, this procedure was performed on an in-hospital basis resulting in high patient cost. This study evaluated the safety and efficacy of pneumatic dilation as an outpatient procedure. Sixty-one procedures were performed on 50 patients at two centers. An overall treatment success rate of 95% (47 of 50 patients) was achieved. Two patients had elective surgical treatment and a third underwent surgery for perforation secondary to dilation. A total of three patients complained of post-procedure chest pain within 4 hours and were hospitalized. Two had perforations; one required surgical repair. The third patient had resolution of symptoms. We conclude that performing balloon dilation as an outpatient procedure is safe, efficacious, and cost effective. PMID- 2110541 TI - The rapid placement of jejunal feeding tubes: the Seldinger technique applied to the gut. PMID- 2110542 TI - Development of a medical-psychiatric program within the private sector. Potential problems and strategies for their resolution. AB - Recent reports regarding the development of combined medical-psychiatric units have primarily involved units operated under the auspices of academic medical centers. Almost no published information is available regarding the fiscal, administrative, or clinical feasibility of operating such programs within the context of the private community hospital setting. This article outlines the organization and development of such a private unit and discusses the various medical, administrative, political, and financial considerations that must be evaluated in planning for the successful operation of medical-psychiatric units within the private sector. PMID- 2110543 TI - A "hateful epileptic" patient in the burn unit. AB - An interdisciplinary team discussed the case of a 31-year-old woman who sustained second- and third-degree burns while having a seizure. She was a difficult patient who elicited a good deal of negative feelings from the staff. The interview raised the possibility of this burn having been a suicidal attempt, and the subsequent discussion centered on effective ways of relating to her pathologic defense mechanisms. The need for a comprehensive approach that took into consideration the biologic, psychologic, and social aspects of her needs became evident to all the participants. PMID- 2110544 TI - Growth hormone and somatomedin-C secretion in patients with polycystic ovarian disease. Their relationships with hyperinsulinism and hyperandrogenism. AB - Nineteen women with polycystic ovarian disease (PCO; 9 obese) and 15 normal ovulatory women (7 obese) were studied at their follicular phase. All patients had an oral glucose tolerance test (OGTT) before and after treatment with gonadotropin-releasing hormone (GnRH) agonist (Buserelin 400 micrograms/die s.c. for 8 weeks) to investigate the relationship between ovarian steroidogenesis and insulin and growth hormone (GH) and insulin-like growth factor (SmC) secretion. Luteinizing hormone, follicle-stimulating, estradiol, androstenedione, testosterone, dehydroepiandrosterone sulfate, cortisol, insulin, GH and SmC were measured basally at the time of OGTT. PCO patients showed higher androgen basal levels than control patients. All subjects showed a normal glycemic response to OGTT. The mean fasting level and area under the curve of plasma insulin were also significantly greater in PCO than in control patients (p less than 0.05), while GH and SmC plasma concentrations did not differ between the groups. Despite a considerable decrease in androgens and the similar levels in both PCO and control women, buserelin treatment did not determine any significant changes of insulin and GH-SmC secretion. GH and SmC did not correlate with ideal body weight (IBW), insulin or androgens, whereas insulin correlated with both testosterone and androstenedione levels (p less than 0.05) and with IBW (p less than 0.01); after the buserelin regimen only IBW remained related to plasma insulin (p less than 0.01). In conclusion results of this study confirm that hyperinsulinism is a characteristic picture of PCO and is related in an unclear way with hyperandrogenism and obesity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110545 TI - A transcribed gene in an intron of the human factor VIII gene. AB - We have identified a CpG island contained within the largest factor VIII intron. This island is associated with a 1.8-kb transcript and, unlike factor VIII, is produced abundantly in a wide variety of cell types. The nested gene is oriented in a direction opposite to that of factor VIII and contains no intervening sequences. A cDNA of 1739 bases was isolated from a human liver library and found to have a GC-rich, long open reading frame. Two computer-assisted methods (Fickett TESTCODE and Staden-McLachlan codon usage) predict that the gene codes for a protein. Two other copies of this gene are located within 1.1 Mb of the factor VIII gene. Northern blot analysis of RNA isolated from hemophilia patients deleted for factor VIII sequences has shown that both the intron gene and at least one other copy of the gene are transcribed. A homologous, transcribed sequence is also present in mice. PMID- 2110546 TI - Efficient linkage of 10 loci in the proximal region of the mouse X chromosome. AB - Interspecific Mus species crosses were used to construct a multilocus genetic map of the mouse X chromosome that extends for more than 50 cM. In these studies, we established the segregation of eight loci in more than 200 backcross progeny from crosses of M. musculus and M. spretus with a common inbred strain (C57BL/6JRos). Genetic divergence at the level of the nucleotide sequences makes these crosses a useful cumulative genetic resource for mapping additional genes defined by genomic or cDNA probes in a highly efficient manner. We have therefore devised a mapping strategy that uses a subset of these backcrosses that are recombinant between successive anchor loci to both localize and order an additional set of six genes without necessarily resorting to an analysis of the entire backcross series. Using this approach, we have defined the linkage of cytochrome b245 beta chain (Cybb), synapsin (Syn-1), and two members of the X-linked lymphocyte regulated gene family (Xlr-1, Xlr-2), as well as DXSmh141 and DXSmh172, two loci defined by random genomic probes. All six loci have been localized to the proximal portion of the mouse X chromosome and their order has been defined as Cybb, Otc, Syn-1/Timp, DXSmh141/Xlr-1, DXSmh172, Hprt, Xlr-2, Cf-9. Gene order was established by minimizing multiple recombination events across the region spanning an estimated 20 cM of the proximal X chromosome. The possible significance of the Xlr loci is discussed with respect to other X-chromosome loci that regulate the immune response. PMID- 2110547 TI - Characterization and chromosomal mapping of a cDNA encoding tryptophan hydroxylase from a mouse mastocytoma cell line. AB - A cDNA library was constructed from RNA prepared from P815 mouse mastocytoma cells and screened for tryptophan hydroxylase. An essentially full-length clone that recognizes a major mRNA species of 1.9 kb in mastocytoma cell lines and in pineal gland, duodenum, and brainstem of the mouse was obtained. The predicted amino acid sequence of this mouse mastocytoma clone showed 97 and 87% identity, respectively, with tryptophan hydroxylase clones isolated from rat and rabbit pineal glands, but the mouse clone contains an unusual 3-amino-acid duplication near the N-terminus and lacks a phosphorylation site. A fragment of the cDNA produced an enzymatically active protein when expressed in Escherichia coli, thus demonstrating that the catalytic domain is included in the C-terminal 380 amino acids. The mouse tryptophan hydroxylase locus, termed Tph, was mapped by Southern blot analysis of somatic cell hybrids and by an interspecific backcross to a position in the proximal half of chromosome 7. Because TPH has been mapped to human chromosome 11, this assignment further defines regions of homology between these mouse and human chromosomes. PMID- 2110548 TI - Human IFN-gamma up-regulates IL-2 receptors in mitogen-activated T lymphocytes. AB - This study examined the role of human recombinant interferon-gamma (rIFN-gamma) in the expression of interleukin-2 receptors (IL-2R) by human T lymphocytes. rIFN gamma enhanced total numbers of IL-2R in mitogen-activated but not resting T cells. Scatchard plot analysis indicated that rIFN-gamma increased both high- and low-affinity receptors, with a predominant effect on the latter. Phytohaemagglutinin (PHA)-activated T cells treated with IFN-gamma showed higher IL-2 binding and greater IL-2 internalization and degradation than cells treated with PHA alone. There was a corresponding increase of mitogen-driven proliferative responses, indicating an increase of functional receptors in IFN treated cultures. IFN-gamma may influence T-cell activation and proliferation by enhancing expression of IL-2R and promoting IL-2 uptake by mitogen-activated lymphocytes. PMID- 2110549 TI - Immunoregulation in the common marmoset, Calithrix jaccus: functional properties of T and B lymphocytes and their response to human interleukins 2 and 4. AB - Non-human primates have been used to study immune function to a much lesser extent than readily available strains of inbred rodents. Nevertheless, in situations where it might be desirable, but impossible, to study human immune responses in vivo, lower primates could provide an acceptable alternative. In order to extent the knowledge of T- and B-lymphocyte function in lower primates, the common marmoset Callithrix jaccus was used as an experimental model. The functional similarities between this species and humans at the level of T-B co operation in the antibody response were examined, and xenoreactive T-lymphocyte clones were obtained from marmoset spleen cells using Epstein-Barr virus (EBV) transformed human B cells as stimulators. These clones could act as helper cells when co-cultured with human B lymphocytes, inducing the secretion of both IgM and IgG. Lymphokine production by mitogen-stimulated marmoset T-cell clones was also examined. Interleukins (IL) 2 and 4 activities were detected in clone supernatants using bioassays and interferon-gamma (IFN-gamma) was detected using a solid-phase ELISA system. However, SDS-PAGE analysis of biosynthetically labelled marmoset and human T-cell clone supernatant proteins revealed major differences between the soluble T-cell products of the two species. The proliferative responses of marmoset T and B cells to recombinant human IL-2 and IL-4 were also examined. Stimulation of [3H]thymidine uptake was detected in both T cell- and anti-IgM-stimulated B-cell cultures with both of the lymphokines. These results suggests that the key components of the antibody response are functionally conserved between lower primates and man and that the common marmoset may be useful as an in vivo model of immune function, particularly with regard to the role of interleukins such as IL-2 and IL-4. PMID- 2110550 TI - pp60c-src protein kinase activity in human gastric carcinomas. AB - We examined pp60c-src protein kinase activity in human gastric carcinoma cell lines and gastric carcinoma tissues as well as normal mucosa. pp60c-src kinase activity was detected in all 5 carcinoma cell lines at various levels. Of 16 gastric carcinoma tissues, 8 showed higher pp60c-src kinase activity in tumor tissues than in corresponding normal mucosa. However, the levels of expression of pp60c-src detected by Western blotting were not always consistent with the activities of pp60c-src protein kinase. These findings suggest that the increase in pp60c-src protein kinase activity might be brought about by post-translational changes. PMID- 2110551 TI - Successful treatment of chaotic atrial tachycardia with oral flecainide. AB - Two infants with chaotic atrial tachycardia diagnosed at birth and at 11 weeks of life, were treated successfully with oral flecainide. Both patients were in heart failure at initiation of therapy. Six months and 17 months later, respectively, they have had no recurrence of chaotic atrial tachycardia, left ventricular function returned to normal and therapy was stopped in both. PMID- 2110552 TI - Selective effects of tocainide in canine acute myocardial infarction. AB - We examined the in vivo electrophysiologic effects of tocainide in canine acute myocardial infarction. We compared the effects of tocainide in infarcted and non infarcted zones. The left anterior descending coronary artery of 8 dogs was ligated and bipolar ventricular electrograms were recorded from a needle electrode placed transmurally in the infarcted zone and from electrodes in the non-infarcted zone. Conduction intervals were measured from the onset of the limb lead QRS to the major deflection of the recorded electrograms in the infarcted and non-infarcted zones. Effective refractory periods were also determined. Measurements were made before, during and after intravenous infusion of tocainide in therapeutic doses 2 hours after infarct. Tocainide prolonged conduction intervals by 26-31% in the infarcted zone at peak (P less than 0.001), but by only 6% in the non-infarcted zone. Similarly, tocainide prolonged the effective refractory period by 27% (P less than 0.001) on the infarcted, but by 8% the non infarcted zone. Tocainide had very slight effects on QRS duration. The present study shows that tocainide had selective effects in the infarcted zone on both conduction and effective refractory period. These selective effects may explain its antiarrhythmic effects in acute myocardial infarction. PMID- 2110553 TI - Superficial migratory thrombophlebitis and the lupus anticoagulant. AB - The lupus anticoagulant is an antiphospholipid antibody found in association with systemic lupus erythematosus and in a variety of other diseases, as well as in healthy individuals. In the laboratory, the antibody interferes with the conversion of prothrombin to thrombin and prolongs the partial thromboplastin time. In vivo, it exerts a procoagulant effect resulting in thrombosis, mainly of the larger veins and arteries. The case of a young woman who developed superficial migratory thrombophlebitis in association with a high titer lupus anticoagulant is presented. Her diagnosis was initially missed because the partial thromboplastin time was not elevated. This appears to have resulted from the use of a specific thromboplastin relatively insensitive to the presence of the antibody. Retesting with a more sensitive reagent showed a markedly prolonged partial thromboplastin time. PMID- 2110554 TI - Pig handler's itch. AB - Forty-six humans who contacted pigs infested with Sarcoptes scabiei were investigated. Thirty (65.2%) had symptoms of sarcoptes scabies, and S. scabiei mites could be recovered from 20 (66.6%) skin scrapings. Itching was the main symptom. People within the age group of 26-35 years were infested the most. Hands and legs were the most common sites of the lesions, which subsided within 2-3 weeks when the infested pigs were treated and the intimate contact with the pigs was prevented. PMID- 2110555 TI - Combination therapy (monomycine and methyluracil) in Leishmania cutis. PMID- 2110556 TI - Differential binding of P. aeruginosa and S. aureus to corneal epithelium in culture. AB - Adherence of bacteria to corneal epithelium is a prerequisite for corneal infection. We used two methods to study the binding of Pseudomonas aeruginosa and Staphylococcus aureus to rabbit corneal epithelial cells in culture. In the first method, rabbit corneal epithelial cells grown on glass slides were incubated with P. aeruginosa or S. aureus (10(7) CFU/ml) at room temperature for 90 min, and the bacterial binding to the epithelial cells was examined by light microscopy. Both P. aeruginosa and S. aureus bound to epithelial cells. P. aeruginosa was bound to the cell periphery whereas S. aureus was bound randomly to the cell surface. In the second method, suspension cultures of corneal epithelial cells were used. In contrast to the findings in cultures on slides, binding pattern with cells in suspension was similar for both species and resembled that for S. aureus in cultures on slides. A much greater number of P. aeruginosa (186 +/- 11 bacteria/epithelial cell) than S. aureus (30 +/- 1.5 bacteria/epithelial cell) bound to epithelial cells grown on glass slides. In contrast, a similar number of P. aeruginosa (25 +/- 5.1) and S. aureus (20 +/- 4.7) bound to epithelial cells grown in suspension cultures. Using either method, Escherichia coli and Streptococcus pyogenes did not bind significantly (less than 5/cell) to corneal epithelial cells. The above methods should prove useful for characterization of bacterial binding to corneal epithelial cells in culture. PMID- 2110557 TI - Effects of hematoporphyrin derivative and light on Y79 retinoblastoma cells in vitro. AB - Retinoblastoma Y79 cells exposed to a hematoporphyrin derivative and light were examined with regard to the production of intracellular lipid peroxide and morphologic changes, in the presence or absence of oxygen. The intracellular lipid peroxide was related to the dose of hematoporphyrin derivative and the duration of photoradiation, under aerobic conditions. The formation of lipid peroxide was not inhibited with superoxide dismutase and catalase, but it was inhibited with mannitol and 1,4-diazabicyclo[2,2,2]octane, which were inhibitors of hydroxyl radicals and singlet oxygen, respectively. The mitochondria were apparently the target organelle in Y79 retinoblastoma cells. PMID- 2110558 TI - Inflammatory mediators in the vitreous humor of AIDS patients with retinitis. AB - We measured levels of protein, of complement-derived anaphylatoxins (C3a, C4a, and C5a), and of the lymphokines interleukin-2 and gamma interferon, in vitreous humor from 10 AIDS patients with vitritis and retinitis (group 1). We compared these measurements with levels in vitreous from 7 patients with vitritis but without AIDS (group 2), 10 patients with vitreous hemorrhages (group 3), and 20 patients with retinal detachments or epiretinal membranes without clinical evidence of vitreal inflammation (group 4). Vitreous humor from 10 AIDS patients had measurable levels of interleukin-2 in three of nine samples, gamma interferon in six of nine samples, C3a and C4a in all ten samples, and C5a in only one of ten samples. Vitreous humor from group 1 did not differ significantly from vitreous from group 2. On the other hand, vitreous from group 1 had significantly higher levels of gamma interferon, C3a, and C4a, and higher ratios of these anaphylatoxins to protein, in comparison to vitreous in groups 3 and 4. The results of this study suggest that vitreous humor from AIDS patients with retinitis contains activated complement and may contain interleukin-2 and gamma interferon. Viral retinitis is associated with the presence of lymphokines in vitreous humor. Additionally, anaphylatoxin and gamma interferon levels, but not interleukin-2 levels, correlate with vitreal inflammation. This is the first study to measure interleukin-2, gamma interferon, and C5a levels in human vitreous humor. PMID- 2110559 TI - A fixed-dose (300 mg) efficacy study of bupropion and placebo in depressed outpatients. AB - Two hundred twenty-four outpatients with major depression entered a 6-week, five center, double-blind trial of bupropion 300 mg/day and placebo. A total of 216 patients were included in the efficacy analysis. In the combined center analysis, greater efficacy for bupropion was found on one or more measures (Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions) at treatment Days 21, 28, 35, and 42. Bupropion was well tolerated; only four adverse events were reported at least 5% more often in the bupropion group than in the placebo group. Six bupropion patients versus 5 placebo patients discontinued treatment because of adverse events. This study extends earlier findings of efficacy for higher-dose treatment in an inpatient population to lower-dose treatment in an outpatient population. PMID- 2110560 TI - A double-blind, placebo-controlled trial of fluvoxamine versus imipramine in outpatients with major depression. AB - The authors employed a double-blind, placebo-controlled design to investigate the effectiveness of fluvoxamine versus imipramine in 54 outpatients with moderate major depression. Fluvoxamine proved superior to placebo but not to imipramine on the Hamilton Rating Scale for Depression and the Montgomery and Asberg Depression Rating Scale. Nausea and hyperarousal were the most common side effects in the fluvoxamine-treated patients. PMID- 2110561 TI - The primary structure of rat liver glycogen synthase deduced by cDNA cloning. Absence of phosphorylation sites 1a and 1b. AB - The cDNA for rat liver glycogen synthase was isolated by screening a rat liver cDNA library constructed in lambda gt11. The cDNA was 2.4 kilobases in length and encoded a protein of 703 amino acid residues with a molecular mass of 80.5 kDa. Comparison of the rat liver and the human muscle sequences show that the amino- and carboxyl-terminal regions are quite divergent as compared to the internal sequences which show an 80% identity. The rat liver carboxyl-terminal region is truncated by 33 residues and has only 46% identity with the muscle sequence but retains the common feature of a low content of hydrophobic amino acids (13%). Phosphorylation sites 1a and 1b, which are the primary targets for phosphorylation by cAMP-dependent protein kinase, are absent in the liver sequence. The presence of these divergent, structurally anomalous carboxyl terminal regions in liver and muscle glycogen synthase suggests the absence of the requirement that they possess a tertiary structure that is integral to that of the protein core. A model is proposed in which this region interacts with a catalytic core to maintain the I state, and in which phosphorylation serves to uncouple this interaction. PMID- 2110562 TI - The structure of the human synapsin I gene and protein. AB - Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton. Human genomic clones containing the full coding sequence of synapsin I were isolated, and the exons were mapped and sequenced. Human synapsin I is encoded by a single copy gene containing 13 exons ranging in size from 58 base pairs to more than 1 kilobase that are unequally distributed over more than 30 kilobases of DNA on the X-chromosome. The differential splicing of the primary synapsin I transcript that generates synapsins Ia and Ib involves alternative use of splice acceptor sites at the last intron-exon boundary. The primary structure of synapsin I is highly conserved between the human, rat, and bovine proteins (95% identity). The intron placement within that primary structure correlates with the previously postulated domain model of the protein. Exon I contains domains A and B, while exon 12 contains almost all of domain D, and exon 13 contains the alternatively spliced domains E and F. Domain C, the central homologous domain implicated in the binding of synapsin I to actin and to synaptic vesicles, is divided into nine exons. PMID- 2110563 TI - Location of the protease-inhibitory region of secretory leukocyte protease inhibitor. AB - Secretory leukocyte protease inhibitor (SLPI) is a two-domain protein that inhibits a wide range of proteases including chymotrypsin, leukocyte elastase, and trypsin. Based on its homology to other protease inhibitors and on x-ray crystallography of an SLPI-chymotrypsin complex it has been proposed that the elastase and chymotrypsin-inhibitory site is in the COOH-terminal domain and that the trypsin-inhibitory site is in the NH2-terminal domain. We have prepared muteins of SLPI by site-directed mutagenesis of a synthetic gene for the protein, followed by expression in Escherichia coli. The protease-inhibitory activities of these muteins indicate that leucine 72 in the COOH-terminal domain is at the inhibitory site for elastase and chymotrypsin. Unexpectedly, our measurements indicate that the trypsin-inhibitory site is not in the NH2-terminal domain. Instead they suggest that leucine 72 is also the inhibitory site for trypsin, even though the amino acid residues at the inhibitory sites of other trypsin inhibitors are almost always either lysine or arginine. PMID- 2110564 TI - DNA photoreactivating enzyme from the cyanobacterium Anacystis nidulans. AB - Photoreactivating enzyme, which specifically monomerizes pyrimidine dimers in UV irradiated DNA, was purified 21,000-fold from the cyanobacterium Anacystis nidulans to apparent homogeneity with 41% overall yield. The enzyme consists of a single protein chain with 53,000 molecular weight. Maximal activity was found at pH 6.2 and 0.1 M NaCl. Purified photoreactivating enzyme exhibits a marked absorption spectrum with a main band in the blue region (maximum 437 nm), a protein band (maximum 266 nm), and a low intensity band above 500 nm. The molar extinction coefficient of native enzyme was estimated 53,000 at 437 nm. The action spectrum for photoreactivation shows maximal activity at 440 nm and correlates closely with the 437-nm absorption band. The enzyme contains two different intrinsic chromophores in equimolar amounts, which were identified as 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) and (reduced) FAD. The low intensity absorption band of native photoreactivating enzyme exhibits a shoulder at 498 and maxima at 588 and 634 nm. This band is attributed to a neutral FAD semiquinone radical which accounts for the major part of the FAD present in dark equilibrated enzyme. Preillumination at 585 nm bleaches the semiquinone spectrum due to formation of fully reduced FAD, but exposure to air in the dark restores the spectrum completely. On preillumination at 437 nm the disappearance of FAD semiquinone is more rapid, indicating that the photoreduction is sensitized by the 8-hydroxy-5-deazaflavin chromophore. The 8-hydroxy-5-deazaflavin and possibly also the reduced FAD chromophore appear to act as a primary photon acceptor in the photoreactivation process. PMID- 2110565 TI - Alveolar epithelial cell plasminogen activator. Characterization and regulation. AB - Intra-alveolar fibrin deposition is one of the pathological hallmarks of acute lung injury. Because alveolar epithelial cells play a central role in the repair process following acute lung injury, this study was undertaken to examine their potential to produce a plasminogen activator (PA). We now report the synthesis and secretion of PA by rat alveolar epithelial cells with the catalytic properties of a urokinase-type (u-PA) rather than tissue-type plasminogen activator. Studies of regulation of epithelial cell u-PA revealed: 1) phorbol myristate acetate (PMA) but not the inactive structural analog 4 alpha-PMA upregulated u-PA synthesis, putatively via the protein kinase C pathway; 2) PMA induction of u-PA activity was substantially inhibited by dexamethasone and completely inhibited by cycloheximide; 3) unstimulated alveolar epithelial cells had no detectable u-PA mRNA, whereas PMA exposure led to activation of the u-PA gene and accumulation of a 2.5-kilobase u-PA mRNA; and 4) cycloheximide did not abolish this induction of u-PA mRNA suggesting that intermediate protein synthesis was not necessary for the activation of transcription. In light of their capacity to promote fibrinolysis and their strategic anatomic location, alveolar epithelial cells are likely to play a key role in the extensive remodelling process that follows acute lung injury. PMID- 2110566 TI - Photoaffinity labeling and partial purification of the beta cell sulfonylurea receptor using a novel, biologically active glyburide analog. AB - An iodinated analog of the sulfonylurea, glyburide, has been synthesized which can be labeled to high specific activity and used to photolabel the sulfonylurea receptor. 5-Iodo-2-hydroxy-"glyburide", has an iodo group replacing the chlorine at position 5 and a methoxy residue replacing the hydroxy group at position 2 on the benzamido ring. This analog retains biologic activity stimulating insulin secretion from a hamster beta cell line (HIT cells) at the same ED50 (0.4 nM) as glyburide. Scatchard analysis demonstrated high and low affinity binding sites on HIT cell membranes (Kd values of 0.36 nM and 277 nM and Bmax values of 1.6 and 100 pmol/mg of membrane protein, respectively). Competitive binding assays with unlabeled glyburide or 5-iodo-2-hydroxyglyburide yield Ki values of 0.5 and 1.0 nM, respectively. The analog can be covalently linked by ultraviolet irradiation to a membrane protein of Mr = 140,000. The photolabeling is completely blocked by unlabeled glyburide or the analog. Two other species of Mr = 65,000 and 43,000 are also photolabeled; these may be the low affinity sites. After photolabeling, the receptor has been purified partially by chromatographic procedures and is suitable for obtaining peptide sequence. The 140,000 molecular weight protein is identified as the sulfonylurea receptor since its binding constant, 0.36 nM, is closely correlated with its ability to stimulate insulin secretion (ED50 congruent to 0.4 nM). PMID- 2110567 TI - Adjunctive hyperbaric oxygen in the treatment of thermal burns. An economic analysis. AB - Current reimbursement for burn care underscores the importance of cost containment in the treatment of burn injuries. We evaluate the economic impact of adjunctive hyperbaric oxygen in burns of 19% to 50% total body surface area in patients admitted to our burn center from January 1982 to July 1987. Length of hospitalization, number of surgical procedures, and total cost of care, exclusive of surgical fees, were examined. Eleven patients did not receive adjunctive hyperbaric oxygen therapy, whereas 10 did. The hyperbaric oxygen-treated group had an average decrease in length of stay of 14.8 days, a reduction of surgical procedures of 39%, and an average saving per case of $31,600. PMID- 2110568 TI - Cytosolic free calcium elevation mediates the phagosome-lysosome fusion during phagocytosis in human neutrophils. AB - Cytosolic free calcium ([Ca2+]i) and fusion of secondary granules with the phagosomal membrane (phagosome-lysosome fusion, P-L fusion) were assessed in single adherent human neutrophils during phagocytosis of C3bi-opsonized yeast particles. Neutrophils were loaded with the fluorescent dye fura2/AM and [Ca2+]i was assessed by dual excitation microfluorimetry. Discharge of lactoferrin, a secondary granule marker into the phagosome was verified by immunostaining using standard epifluorescence, confocal laser scanning and electron microscopy. In Ca2(+)-containing medium, upon contact with a yeast particle, a rapid rise in [Ca2+]i was observed, followed by one or more Ca2+ peaks (maximal value 1,586 nM and median duration 145 s): P-L fusion was detected in 80% of the cells after 5 10 min. In Ca2(+)-free medium the amplitude, frequency and duration of the [Ca2+]i transients were decreased (maximal value 368 nM, mostly one single Ca2+ peak and median duration 75 s): P-L fusion was decreased to 52%. Increasing the cytosolic Ca2+ buffering capacity by loading the cells with MAPT/AM led to a dose dependent inhibition both of [Ca2+]i elevations and P-L fusion. Under conditions where basal [Ca2+]i was reduced to less than 20 nM and intracellular Ca2+ stores were depleted, P-L fusion was drastically inhibited while the cells ingested yeast particles normally. P-L fusion could be restored in Ca2(+)-buffered cells containing ingested particles by elevating [Ca2+]i with the Ca2(+)-ionophore ionomycin. The present findings directly indicate that although the ingestion step of phagocytosis is a Ca2(+)-independent event, [Ca2+]i transients triggered upon contact with opsonized particles are necessary to control the subsequent fusion of secondary granules with the phagosomal membrane. PMID- 2110570 TI - Brownian motion of inert tracer macromolecules in polymerized and spontaneously bundled mixtures of actin and filamin. AB - By use of light microscopy and fluorescence photobleaching recovery, we have studied (a) structures that form in a system composed of copolymerized rabbit muscle actin and chicken gizzard filamin and (b) the Brownian motion of inert tracer macromolecules in this matrix. We have used as tracers size-fractionated fluorescein-labeled ficoll and submicron polystyrene latex particles. In F-actin solutions, the relative diffusion coefficient of the tracer was a decreasing function of both tracer size and actin concentration. Also, a percolation transition for latex particle mobility was found to follow a form suggested by Ogston (Ogston, A. G. 1958. Trans. Faraday Soc. 54:1754-1757) for random filament matrices. The inclusion of filamin before polymerization resulted in increased tracer mobility. Below a filamin dimer-to-actin monomer ratio of 1:140, no structural features were observed in the light microscope. At or above this ratio for all actin concentrations tested, a three-dimensional network of filament bundles was clearly discriminated. Latex particles were always excluded from the bundles. By use of a dialysis optical cell in which polymerization could be initiated with very little hydrodynamic stress, we found that filamin can spontaneously bundle F-actin. A simple physical picture explains how dynamics can affect the structural result of coassembly and provides a further hypothesis on the balance between random filament cross-linking and large-scale bundling. Control of this balance may be important in cytoplasmic motile events. PMID- 2110569 TI - Functional studies of the domains of talin. AB - The protein talin has two domains of approximately 200 and 47 kD, which can be cleaved apart by a variety of proteases. To examine the function of these two structural domains of talin, we have digested purified talin with a calcium dependent protease and separated the resulting fragments chromatographically. Both fragments were radioiodinated and used to probe Western blots of whole fibroblasts and chicken gizzard extracts. The large talin fragment bound to vinculin and metavinculin. The small fragment did not demonstrate any binding in this assay. The fragments were labeled fluorescently and microinjected into fibroblasts in tissue culture. The large talin fragment incorporated quickly into focal adhesions where it remained stable for at least 14 h. The small fragment associated with focal adhesions of fibroblasts but was also distributed diffusely in the cytoplasm and the nucleus. These experiments suggest that talin has at least two sites that contribute to its localization in focal adhesions. Intact talin microinjected into Madin-Darby bovine kidney epithelial cells localized to the focal adhesions but was excluded from the zonulae adherentes, despite the localization of vinculin to both of these sites. In contrast, the large talin fragment, when microinjected into these epithelial cells, incorporated into both focal adhesions and zonulae adherentes. The difference in localization between the large talin fragment and intact talin seems to be due to the removal of the small domain. This difference in localization suggests that talin binding sites in zonulae adherentes have limited accessibility. PMID- 2110571 TI - Biogenesis of synaptic vesicle-like structures in a pheochromocytoma cell line PC 12. AB - The presence of unique proteins in synaptic vesicles of neurons suggests selective targeting during vesicle formation. Endocrine, but not other cells, also express synaptic vesicle membrane proteins and target them selectively to small intracellular vesicles. We show that the rat pheochromocytoma cell line, PC12, has a population of small vesicles with sedimentation and density properties very similar to those of rat brain synaptic vesicles. When synaptophysin is expressed in nonneuronal cells, it is found in intracellular organelles that are not the size of synaptic vesicles. The major protein in the small vesicles isolated from PC12 cells is found to be synaptophysin, which is also the major protein in rat brain vesicles. At least two of the minor proteins in the small vesicles are also known synaptic vesicle membrane proteins. Synaptic vesicle-like structures in PC12 cells can be shown to take up an exogenous bulk phase marker, HRP. Their proteins, including synaptophysin, are labeled if the cells are surface labeled and subsequently warmed. Although the PC12 vesicles can arise by endocytosis, they seem to exclude the receptor-mediated endocytosis marker, transferrin. We conclude that PC12 cells contain synaptic vesicle-like structures that resemble authentic synaptic vesicles in physical properties, protein composition and endocytotic origin. PMID- 2110572 TI - Effects of verapamil on diurnal and thyrotropin-releasing hormone-stimulated prolactin levels in man. AB - The effects of the calcium entry blocker verapamil on the 24-h profile of PRL secretion and on the PRL response to TRH were investigated in six healthy volunteers. Verapamil (120 mg, three times daily) was administered orally for 1 week. In all subjects both basal and TRH-stimulated PRL levels were markedly elevated by verapamil. The average diurnal PRL concentration was increased from 13.0 +/- 2.0 micrograms/L to 25.2 +/- 4.4 (mean +/- SE; P = 0.02). Diurnal rhythm and pulsatility of PRL secretion were seen both before and during verapamil administration. Mean peak PRL concentrations after TRH injection (200 micrograms, iv) were significantly increased from 72.6 +/- 11.6 to 115.2 +/- 16.8 (P less than 0.01), and the mean area under the PRL concentration-time curves from 4332 +/- 962 micrograms/L.120 min to 6975 +/- 1334 (P = 0.01). The data are in striking contrast with previous findings from in vitro studies where verapamil has been reported to block calcium-mediated stimulus-secretion coupling and inhibit hormone secretion from pituitary cells. Interference with other PRL regulating mechanisms may account for the demonstrated verapamil-induced PRL secretion in vivo. PMID- 2110573 TI - Serum thyrotropin and prolactin in the syndrome of generalized resistance to thyroid hormone: responses to thyrotropin-releasing hormone stimulation and short term triiodothyronine suppression. AB - Serum TSH and PRL levels and their response to TRH were measured in 11 patients with generalized resistance to thyroid hormone (GRTH), 6 euthyroid subjects, and 6 patients with primary hypothyroidism. TSH and PRL levels and their response to TRH were also measured after the consecutive administration of 50, 100, and 200 micrograms T3 daily, each for a period of 3 days. Using a sensitive TSH assay, all GRTH patients had TSH values that were elevated or within the normal range. On the basis of a normal or elevated TSH level, GRTH patients were classified as GRTH-N1 TSH (5 patients) or GRTH-Hi TSH (6 patients), respectively. Only GRTH patients with previous thyroid ablative therapy had basal TSH values greater than 20 mU/L. TSH responses, in terms of percent increment above baseline, were appropriate for the basal TSH level in all subjects. No GRTH patient had an elevated basal PRL level. PRL responses to TRH were significantly increased only in the hypothyroid controls compared to values in all other groups. On 50 micrograms T3, 7 of 12 (58%) nonresistant (euthyroid and hypothyroid) and 1 of 11 (9%) resistant subjects had a greater than 75% suppression of the TSH response to TRH. On the same T3 dose, 2 of 12 (17%) nonresistant and 4 of 11 (36%) resistant subjects had a greater than 50% suppression of the PRL response to TRH. On 200 micrograms T3, all subjects, except for 1 with GRTH, had a greater than 75% suppression of the TSH response to TRH. On the same T3 dose, while 11 of 12 (92%) nonresistant subjects had a greater than 50% reduction of the PRL response to TRH, only 3 of 10 (30%) resistant patients showed this degree of suppression (P less than 0.005). Without previous ablative therapy, serum TSH in patients with GRTH is usually normal or mildly elevated. The TSH response to TRH is proportional to the basal TSH level and is suppressed by exogenous T3. However, on 200 micrograms T3 basal TSH was not detectable (less than 0.1 mU/L) in all euthyroid subjects, but it was measurable in three of four GRTH patients with normal TSH levels before T3 treatment. PRL levels in GRTH are normal even when TSH is elevated. The PRL response to TRH is not increased in GRTH. In all subjects, exogenous T3 suppresses the PRL response to TRH to a lesser degree than the TSH response, but this difference is much greater in patients with GRTH. PMID- 2110574 TI - Growth hormone does not inhibit its own secretion during prolonged hypoglycemia in man. AB - In man, continuous infusion of GH-releasing hormone (GHRH) does not sustain GH secretion, unlike prolonged hypoglycemia. To further evaluate this difference in the stimulation of GH release we measured GH concentrations for 3 h during prolonged insulin-induced hypoglycemia and GHRH-(1-29)NH2 (100 micrograms/h) infusion in normal individuals. We also assessed the GH response to combined and separate administration of insulin and GHRH. Plasma GH levels increased during prolonged hypoglycemia and remained elevated for the third hour (22-24 micrograms/L). GH concentrations increased during GHRH infusion, peaked at 60 min (23.5 micrograms/L), and rapidly declined. Thus, our findings confirmed that prolonged hypoglycemia, unlike GHRH infusion, sustained elevated GH levels and that these high levels did not appear to influence GH secretion from the pituitary. Changes in FFA did not account for the sustained GH secretion. FFA levels initially declined during insulin infusion, but after 3 h of hypoglycemia they returned to near-basal values (basal, 0.1 +/- 0.02 g/L; 180 min, 0.09 +/- 0.02). The maximal GH concentration attained during the combined insulin and GHRH test was significantly higher than that with the insulin tolerance test or GHRH test (insulin plus GHRH, 71.9 +/- 13.5; insulin tolerance test, 34.2 +/- 2.9; P less than 0.025; GHRH test, 27.9 +/- 3.2; P less than 0.02), indicating an additive effect on GH secretion. These data suggest that insulin-induced hypoglycemia stimulates GH secretion through a mechanism partly independent of GHRH. The release from somatostatin inhibition and stimulation through other neuropeptides (e.g. galanin) is suggested as possible causes of hypoglycemia induced GH secretion. PMID- 2110575 TI - Lack of effect of gastric inhibitory polypeptide on hepatic and extrahepatic insulin action. AB - To assess the influence of enteric factors on insulin action, seven lean healthy subjects were studied under conditions of hyperinsulinemic euglycemic glucose clamp, double isotope administration, and enteral vs. parenteral glucose infusion. In random order, glucose and mannitol radiolabeled with [2-3H]glucose were infused intraduodenally for 4 h while the systemic rate of glucose turnover was assessed by [6-14C]glucose. During the final hour of the study, plasma glucose, insulin, C-peptide, glucagon, cholecystokinin, and neurotensin were similar under both experimental conditions. Despite an increase in gastric inhibitory polypeptide concentration during combined enteral and iv glucose infusion to levels that mimicked meal ingestion, total glucose infusion rate, insulin-induced stimulation of glucose uptake, and insulin-induced suppression of hepatic glucose release were comparable to those observed during iv glucose administration. These data indicate that under conditions of modest hyperinsulinemia and euglycemia, gastric inhibitory polypeptide did not influence hepatic or extrahepatic insulin action. PMID- 2110576 TI - Serum inhibin concentrations before and during gonadotropin treatment in men with hypogonadotropic hypogonadism: physiological and clinical implications. AB - We measured by RIA the inhibin concentrations in the sera of 20 men with hypogonadotropic hypogonadism before and during treatment with gonadotropins in order to determine the role of gonadotropins in the control of inhibin secretion and the utility of the serum inhibin concentration in assessing the spermatogenic response to gonadotropin treatment in these patients. Before treatment the mean serum inhibin concentration in the 20 hypogonadotropic men as a group (391 +/- 49 U/L) was significantly lower (P less than 0.001) than that in 27 normal men (741 +/- 52 U/L). In the 7 men whose hypogonadism was of postpubertal onset, the mean serum inhibin concentration (559 +/- 69 U/L) was not significantly lower than that in normal men. In the 13 men whose hypogonadism was of prepubertal onset, the serum inhibin level was significantly lower [381 +/- 74 U/L (P less than 0.01) in the 7 without a history of cryptorchidism and 207 +/- 46 U/L (P less than 0.01) in the 6 with a history of cryptorchidism]. All 20 patients were azoospermic or severely oligospermic and had distinctly subnormal serum testosterone concentrations, even those whose serum inhibin values were normal. In the 7 patients with postpubertal hypogonadism, treatment with hCG alone for 6 months increased the serum testosterone concentration and maximum sperm count to normal, even though the previously normal inhibin concentration was not increased further. In the 13 patients with prepubertal hypogonadism, treatment with hCG alone increased the serum inhibin concentration, and combined treatment with hCG and human menopausal gonadotropin (hMG) increased inhibin further, to well within the normal range (742 +/- 143 U/L) in the patients without a history of cryptorchidism and to just within the normal range (487 +/- 96 U/L) in those with such a history. In the 7 patients with prepubertal hypogonadism but no history of cryptorchidism, treatment with hCG and hMG increased the maximum sperm count to normal in 5. In the 6 patients with prepubertal hypogonadism who did have a history of cryptorchidism, hCG and hMG treatment produced a normal sperm count in only 1. Of 12 patients whose serum inhibin level was more than 300 U/L before treatment, 11 developed a normal maximum sperm count in response to treatment, but of 8 patients whose inhibin concentration was less than 300 U/L before treatment, only 2 developed a normal sperm count in response to treatment (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2110577 TI - Changes in biochemical markers of osteoblastic activity during the menstrual cycle. AB - Serum levels of osteocalcin [OC; bone Gla protein (BGP)] and bone alkaline phosphatase (B-AP) are both correlated to osteoblastic activity, which may be regulated by several hormones, including estrogen, 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3], and PTH. Estrogen shows reproducible variations during the menstrual cycle, while available data on variations in serum 1,25-(OH)2D3 and serum immunoreactive PTH show midcyclic increases or no changes. In the present study we evaluated osteoblastic activity by measuring serum OC and B-AP during the menstrual cycle in eight healthy women, aged 20-47 yr. The cycles were synchronized by LH peaks, and follicular and luteal periods were normalized by lengths. Repeated measures analysis of variance showed that serum OC varied significantly (P less than 0.05), with highest levels during the luteal period. Although the same pattern was seen for serum B-AP, the variation just failed to reach significance (P less than 0.10), but the mean level was significantly higher during the luteal than during the follicular period (P less than 0.05). Gonadotropins and ovarian sex hormones showed significant variations. There were no significant changes in serum vitamin D-binding protein, serum total and free 1,25-(OH)2D3 index, or serum immunoreactive PTH-(1-84), but serum levels of somatomedin-C showed a significant variation, with the highest level during the luteal period (P less than 0.05). Blood levels and urinary excretion of minerals exhibited no significant variations. Cross-correlation studies between OC and estradiol showed the highest correlation coefficient, when OC was lagged about 7 days after estradiol (r = 0.69; P less than 0.05). Moreover, a high correlation was found between OC and somatomedin-C when matched at concurrent time points (r = 0.76; P less than 0.01). No significant correlations were found between the other calcium-regulating hormones and OC when matched at concurrent time points. In conclusion, we found a significant effect of the menstrual cycle on the serum levels of two osteoblastic bone markers, OC and B-AP. The changes indicated that osteoblastic activity is higher during the luteal period. However, whether the changes are caused by direct or indirect effects of the fluctuations in calciotropic hormones is still unresolved. PMID- 2110578 TI - Persistence of concordant luteinizing hormone (LH), testosterone, and alpha subunit pulses after LH-releasing hormone antagonist administration in normal men. AB - LHRH antagonists suppress pituitary and gonadal function by competing with endogenous LHRH for binding to gonadotroph receptors. To determine the mechanism of suppression of gonadotropin secretion we studied the effects of a single dose of a LHRH antagonist on the pulsatile activity of serum bioactive LH (Bio-LH), immunoreactive LH (IR-LH), alpha-subunit, and testosterone for 24 h in normal men. The LHRH antagonist, Nal-Glu [( Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg5,DGlu6-(AA), DAla10]LHRH) was given as a single sc injection of 5 mg to five normal men. Blood samples were collected every 10 min during a 10-h baseline period and for 14 h after administration of the antagonist. IR-LH, alpha-subunit, and testosterone were measured in triplicate, and Bio-LH in duplicate. Pulses were then evaluated using Cluster analysis; all replicates were entered in the pulse analysis. After administration of the Nal-Glu antagonist, IR-LH levels decreased (P less than 0.001) from 2.81 +/- 0.06 at baseline to a nadir of 0.75 +/- 0.02 U/L. Bio-LH levels followed the same pattern, decreasing by 89% (P less than 0.001) from 4.54 +/- 0.13 to a nadir of 0.51 +/- 0.13 U/L 6.8 h after the injection of Nal-Glu. In contrast, serum alpha-subunit levels did not change (P greater than 0.05) during the 14-h period after antagonist administration (0.85 +/- 0.01 and 0.75 +/- 0.01 microgram/L before and after Nal-Glu, respectively). Serum testosterone levels decreased by more than 80%, from 17.6 +/- 0.2 at baseline to a mean nadir of 3.3 +/- 0.7 nmol/L 12.8 h after Nal-Glu administration. Pulse frequency and the number of significant pulses remained the same for all of the measured hormones during the 10-h baseline period and the 14 h after Nal-Glu administration. In contrast, the pulse amplitude of IR-LH, Bio-LH, and testosterone decreased significantly after injection of the antagonist. The pulse amplitude of the alpha subunit also declined, albeit not significantly. Coincidence analysis revealed that during both the 10-h baseline and the 14-h post-Nal-Glu period there was a highly significant (P less than 10(-5) nonrandom synchrony between peaks of IR LH, Bio-LH, alpha-subunit, and testosterone. These results suggest that coordinate pulsatile secretion of IR-LH, Bio-LH, and testosterone persists after the administration of 5 mg Nal-Glu LHRH antagonist.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2110579 TI - Superficial migratory thrombophlebitis and factor XII deficiency. AB - A patient with painful migratory erythematous nodules for 7 years is presented. The nodules, which were localized on the lower and upper extremities, progressed to palpable cords. Multiple venograms showed no evidence of deep vein thrombosis. Skin biopsy specimens were diagnostic of superficial thrombophlebitis. There was no evidence of internal malignancy. Extensive evaluation for an underlying hypercoagulable state was remarkable for a factor XII level 17% of normal. The patient was unresponsive to a wide range of treatments. The recalcitrant nature of his disease and lack of deep venous involvement are unique. An underlying hypercoagulable state should be considered when the diagnosis of superficial migratory thrombophlebitis is considered. PMID- 2110580 TI - Juvenile chronic granulocytic leukemia, juvenile xanthogranulomas, and neurofibromatosis. Case report and review of the literature. AB - A 22-month-old boy had xanthomatous skin lesions, neurofibromatosis, and chronic granulocytic leukemia. Histologic examination of the xanthomatous skin lesions disclosed juvenile xanthogranulomas. Twenty-three previously published cases of this association are reviewed. PMID- 2110581 TI - Focal epilepsies: HM-PAO SPECT compared with CT, MR, and EEG. AB - Regional cerebral blood flow (rCBF) was evaluated quantitatively by 99mTc hexamethyl propyleneamine oxime and single photon emission CT (SPECT) during the interictal phase in 52 patients with focal epilepsy. The results were compared with those obtained by electroencephalography (EEG), CT, and magnetic resonance (MR) imaging. Twenty-four of the 52 patients had one area of local hypoperfusion whereas 7 patients showed an area of local hyperperfusion. In 20 of the 52 patients, both reduced and elevated rCBF values were found. One patient had a normal perfusion pattern. The SPECT findings correlated well with the foci shown by EEG, both with regard to the sides affected and the locations of the regions of altered perfusion. The MR images showed focal lesions in only approximately one-half of the patients examined, and CT in even fewer. PMID- 2110582 TI - pH regulation of urease levels in Streptococcus salivarius. AB - Potential mechanisms for regulation of urease levels in Streptococcus salivarius were examined, including: induction by urea, nitrogen or carbon source repression, and effects of pH and CO2 (because CO2 enrichment enhanced urease detection on urea agar plates). Regulation by either pH or CO2 was confirmed by comparison of the urease accumulation pattern during anaerobic growth under CO2 with that under N2. Under CO2, there was an initial buffering plateau at pH 6.2 and a rate of Streptococcus salivarius urease accumulation three-fold that under N2, with a pH 7.6 plateau. With both gas phases there was also an increase in the rate of urease appearance coincident with the decrease in medium pH following the pH plateau. The effects of pH, CO2, and HCO3- on urease levels and on growth were separately assessed by culture in media containing 0, 25, 100 mmol/L KHCO3 buffered at different pH levels. There was an inverse relationship between the logarithm of the urease level after 24-hour growth and the pH during growth-the urease specific activity was 100-fold higher at pH 5.5, compared with pH 7.0 and above. HCO3-/CO2 (100 mmol/L) had little effect on urease levels, but was essential for growth at pH 5.5. There was no significant urease induction by urea, or repression by ammonia or glucose. There was also evidence of pH regulation of urease levels in some staphylococci, Klebsiella pneumonia, and Corynebacterium renale, but not in Actinomyces naeslundii and several other species. We conclude that the external pH is a major factor regulating urease levels in S. salivarius and possibly some other species-a mechanism equivalent to urease repression by OH-. PMID- 2110583 TI - Evaluation of mutagenicity of restorative dental materials using the Ames Salmonella/microsome test. AB - Compounds of five commercially available dental material kits were examined for mutagenic potential by use of the Ames Salmonella/microsome test. Dimethyl sulfoxide (DMSO) was used as the solvent for all materials, except MONO-LOK2 Primer and Right-On Activator, which were dissolved in 95% ethanol. The Tenure, Fuji, and Gluma materials were initially screened at 2 mg (solids) or 2 microL (liquids) per plate, without S9 (Aroclor 1254-induced rat liver microsomes), and dose-response studies were conducted for those materials showing potential mutagenicity. The components of three dental kits, MONO-LOK2, Right-On, and Gluma, were further examined, both with and without S9 activation, at doses of 0.2, 4, 20, 100, 500, and 2500 micrograms (nL for liquid components) per plate. The data showed no mutagenic potential for the components of Fuji Glass Ionomer (Type III), Tenure Dentin Bonding System, and MONO-LOK2 kits, or Right-On Paste. However, Gluma 3, a component of the Gluma/Lumifor Bonding System, exhibited mutagenic activity in a dose-response manner. The mutagenicity of Gluma 3 was demonstrated in repeated experiments. Gluma 4 and the resin of the Gluma dental kit, as well as Right-On Activator, caused a slight increase in the number of revertants, and judgment regarding their mutagenicity could not be made conclusively. The results of this study indicate that some commercial dental materials may not have been adequately tested for mutagenicity, and that a reliable test program for evaluation of mutagenicity of dental materials is needed so that their safe use in dental practice can be ensured. PMID- 2110584 TI - Managing inpatient clinical nutrition services: a comprehensive program assures accountability and success. AB - A major challenge facing clinical dietitians today is justifying inpatient clinical nutrition services. To meet this challenge, a comprehensive program for the delivery and management of clinical nutrition services was developed at Yale New Haven Hospital. It is based on seven nutritional risk factors--age, diagnosis/treatment, diet, metabolic or mechanical problems, significant lab values, pertinent medications, and weight for height. These risk factors are used to categorize patients into one of seven classifications. In essence, this classification system is the screening tool used to provide the foundation for standards of practice and nutrition assessment and intervention. The inherent advantage of such a program is that it identifies patients at high nutritional risk, regardless of wide variations in patient population or diagnosis. It also provides standardized criteria for evaluating quality of care, patient acuity, and productivity and staffing. Clinical nutrition services can then be measured for both quality and quantity. Because protein-calorie malnutrition poses a serious threat to cost containment and quality patient care, this type of program can appeal to hospital administrators, physicians, and site visitors alike. It can serve as an adaptable model for the delivery and management of inpatient clinical nutrition services in a wide variety of health care facilities. PMID- 2110585 TI - A rapid bioassay for chemicals that induce pro-oxidant states. AB - A new bioassay has been developed that allows rapid, sensitive detection of chemicals such as paraquat and adriamycin, which manifest their acute toxicity, mutagenicity or carcinogenicity by inducing a pro-oxidant state in vivo. Submitochondrial particles isolated from bovine myocardium are used to catalyze NADH-dependent enzymatic reduction of these chemicals to free radicals. The highly reactive species generated in this system reduce molecular dioxygen to the superoxide anion radical, which is detected spectrophotometrically using the adrenochrome reaction. The anticancer drug adriamycin, the herbicides paraquat and diquat, the analytical dye sulfonazo III, and the experimental carcinogen 4 nitroquinoline-N-oxide have been used to test the sensitivity of this new method. This assay can be used to screen fresh water samples for the presence of pollutants that can generate oxygen-centered free radicals in vivo, or to test newly synthesized chemicals for this activity, and may therefore be valuable for environmental monitoring and preliminary toxicity evaluation of industrial or pharmaceutical products. PMID- 2110586 TI - Quantitative immunohistochemistry of synaptophysin in human neocortex: an alternative method to estimate density of presynaptic terminals in paraffin sections. AB - Currently available specific synaptic markers have made it possible to estimate the synaptic density by immunochemical techniques. In the present study we labeled the neocortical presynaptic terminals in histological sections of human autopsy tissue with a monoclonal antibody against synaptophysin. The characteristic granular neuropil reaction was quantified by measuring the average optical density (OD) in the different layers of the parietal cortex with the aid of image analysis equipment. The raw neuropil OD was corrected by subtracting the OD of the white matter in the same section. Our study showed that consistent microdensitometric results can be obtained on 5-microns paraffin sections from specimens with less than 8 hr of post-mortem time before fixation, incubated with 5 micrograms/ml of anti-synaptophysin. The corrected OD measurements were slightly larger in neocortical layers II, III, and V than in layers I, IV, and VI, but the differences were not statistically significant. In area 17, layer IV was denser than the others. We conclude that with certain precautions this method can be used to measure relative amounts of synaptophysin-like immunoreactivity and to infer the density of presynaptic boutons in human situations and in animal models. PMID- 2110587 TI - Psophocarpus tetragonolobus agglutinin reveals N-acetyl galactosaminyl residues confined to endothelial cells and some epithelial cells in human tissues. AB - We studied the binding of Psophocarpus tetragonolobus agglutinin (PTA) conjugates to human adult tissues. In all kidney specimens studied, PTA bound in a blood group-independent way to endothelia in glomerular and intertubular capillaries as well as in larger vessels. In addition, a heterogeneous binding to collecting duct cells was seen. In specimens of human smooth, cardiac, and skeletal muscle, cerebellum, lung, thyroid gland, liver, proliferative endometrium, and placenta, PTA bound only to endothelial of capillaries and larger vessels. In epidermis and gingiva, PTA conjugates additionally revealed reactivity with keratinocytes. Similarly, in salivary gland, urinary bladder, gastrointestinal tract, mammary gland, and renal pelvis, PTA reacted with some epithelial cell layers. The PTA conjugates gave an even cell surface membrane staining of cultured umbilical vein endothelial cells. Lectin-affinity binding of radioactively surface-labeled endothelial cells showed that PTA and Ulex europaeus I agglutinin (UEA-I) recognized related major cell surface glycoproteins. The results with PTA conjugates show that certain N-acetyl galactosaminyl residues are, in addition to some epithelial cells, confined to endothelial cells in human tissues. PMID- 2110588 TI - Visualization of glycosaminoglycans in rat incisor predentin and dentin with cetylpyridinium chloride-glutaraldehyde as fixative. AB - Using cetylpyridinium chloride (CPC) in glutaraldehyde as fixative, we observed sinuous fiber-like structures 300-500 nm long and 7-14 nm thick in the spaces between the collagen fibers of rat incisor predentin. Small granules and fibrils were also detected. Electron-dense vesicles were seen inside the odontoblast processes. The plasma membrane was irregularly stained with material that adhered to its surface. In demineralized dentin, needle-like structures were seen at the periphery of globular structures which were not stained. Staining the sections with Alcian blue did not greatly improve the visualization of CPC-precipitated glycosaminoglycans. The specificity of staining was assessed on serial sections by selective dissociation of glycosaminoglycan aggregates with 2 M calcium chloride and their digestion by bovine testicular hyaluronidase. The glycosaminoglycans were probably combined with lipids, because treatment of the sections with a chloroform/methanol mixture removed the CPC-induced precipitates from both predentin and dentin. PMID- 2110589 TI - Clinical analysis of 3160 patients with epidemic non-A and non-B hepatitis in Xinjiang of China. AB - In this paper, the patients were from in-patient in epidemic area. The diagnosis was made by excluding other type of virus hepatitis, and has been proved that it is Epidemic non-A and non-B Hepatitis (ENANB.H) and it was spread by gastrointestinal tract. The mode of transmission was similar to hepatitis A. The clinical manifestations and abnormality liver functions were mild than hepatitis A or B. Most of them were young and middle-aged people. The pregnant women were more susceptible to this type of hepatitis and the mortality was higher. The hemorrhage may be primary factor of the death of ENANB.H. The histological findings were inflammation in the portal area, Cholestasis and Sportt-patchy necrosis. On transmission electron microscope (TEM), the virus particle, 26-30 nm, presented in cytoplasm. The patients were followed up during the convalescence, which tend to chronization. It is reported that ENANB.H has been epidemic in neighbouring countries-India, Burma, Nepal, Soviet and Pakistan etc for ten years. Since 1980, the sporadic epidemic has presented in south Xinjiang. The outbreak epidemic was presented from Sep. 1986 to May 1988, in this paper the clinical manifestations were reported. PMID- 2110590 TI - [Clinical and etiological studies of tsutsugamushi disease in Miyazaki district- correlation of serological type of R. tsutsugamushi to clinical feature]. AB - The correlation of pathogenic and immunologic characteristics of Rickettsia tsutsugamushi to clinical findings of patients with tsutsugamushi disease in Miyazaki was investigated. In two immunological types, Hirano type strains seemed to have higher virulence to mice than Irie from the findings during the course of infection and on autopsy. A strain of Hirano type was so virulent as to succumb to the infection. As to clinical findings, incidence of hepatomegaly was slightly higher in Hirano type patients than Irie, which is one of the signs in severe type tsutsugamushi disease. This was supported by the higher mean value and frequent appearance of abnormality in liver function test, sGOT, sGPT and LDH, in this type of patients. PMID- 2110591 TI - Purification of tryptase from a human mast cell line. AB - The neutral protease tryptase has been isolated from a human mast cell line, HMC 1. The HMC-1 line was established from the peripheral blood of a patient with mast cell leukemia and maintained as continuously proliferating clones in vitro and as solid mast cell tumors in nude mice. HMC-1-derived tryptase was purified by sequential chromatography on Dowex 1, DEAE 5 PW, and heparin-agarose. Purified tryptase has an apparent molecular weight of 150,000, as determined by molecular sieve HPLC, but migrates as a doublet of bands of 32/35,000 on SDS-PAGE gels. Maximal enzymatic activity was observed at pH 8.5. Cleavage of tosyl-L-arginine methyl ester by purified tryptase was inhibited by dansyl-L-glutamyl-glycyl-L arginine chloromethyl ketone 2 HCl, HgCl2, tosyl-L-lysine chloromethyl ketone, leupeptin, and PMSF but not by benzamidine, aprotinin, tosyl-L-phenyl-alanine chloromethyl ketone, soybean trypsin inhibitor, human plasma, ovomucoid inhibitor, or lima bean trypsin inhibitor. Microsequencing of purified tryptase yielded an amino terminal sequence that was identical to that previously reported for human pituitary-derived tryptase. PMID- 2110592 TI - Managing operating room budget variances. AB - Credibility, power, and the ability to obtain greater departmental resources are three benefits of managing the operating room (OR) department's operating budget effectively. Still, few resources exist to help novice as well as seasoned OR directors grapple with the practicalities of maintaining their budget after the annual budget process is completed. The authors examine how astutely controlling personnel, materials, and services budget variances will result in hospital administrators "hearing" and approving an OR director's requests for resources more readily, staff and physicians who enjoy the benefits of better-staffed services and new technology, and an OR director with a reputation as an effective department head among peers in the hospital. PMID- 2110593 TI - Identification of primary tumour site by immunolocalization of progastricsin in metastatic adenocarcinoma. AB - The aspartic proteinase zymogen, progastricsin, which occurs in normal gastroduodenal mucosa and prostate, has been localized by the immunogold-silver method in formalin-fixed, paraffin-embedded sections of metastatic adenocarcinoma in lymph nodes and liver, the primary site being known in each case. Progastricsin was demonstrated in 16 of 84 lymph node metastases, including 7 of 17 from stomach, 2 of 2 from prostate, and 7 of 65 from other sites. Progastricsin was also found in 19 of 98 hepatic metastases, including 8 of 22 from stomach, 6 of 24 from pancreas, and 5 of 52 from other sites. The presence of progastricsin in a metastasis correlated well with a primary tumour in the stomach or prostate or, less significantly, pancreas. Immunolocalization of progastricsin in a histological section of metastatic adenocarcinoma may help to locate the primary site. PMID- 2110594 TI - Evidence for two K+ currents activated upon hyperpolarization of Paramecium tetraurelia. AB - Hyperpolarization of voltage-clamped Paramecium tetraurelia in K+ solutions elicits a complex of Ca2+ and K+ currents. The tail current that accompanies a return to holding potential (-40 mV) contains two K+ components. The tail current elicited by a step to -110 mV of greater than or equal to 50-msec duration contains fast-decaying (tau approximately 3.5 msec) and slow-decaying (tau approximately 20 msec) components. The reversal potential of both components shifts by 55-57 mV/10-fold change in external [K+], suggesting that they represent pure K+ currents. The dependence of the relative amplitudes of the two tail currents on duration of hyperpolarization suggests that the slow K+ current activates slowly and is sustained, whereas the fast current activates rapidly during hyperpolarization and then rapidly inactivates. Iontophoretic injection of a Ca2+ chelator, EGTA, specifically reduces slow tail-current amplitude without affecting the fast tail component. Both K+ currents are inhibited by extracellular TEA+ in a concentration-dependent, noncooperative manner, whereas the fast K+ current alone is inhibited by 0.7 mM quinidine. PMID- 2110595 TI - Comparison of the effects of bilobol and 12-O-tetradecanoylphorbol-13-acetate on skin, and test of tumor promoting potential of bilobol in CD-1 mice. AB - Bilobol, isolated from ginkgo fruit pulp, has been noted to be a strong skin irritant like 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor-promoter in the skin. A comparative investigation of morphological changes induced by bilobol and TPA induced in the skin of CD-1 mice, and an assessment of the skin tumor promoting potential of bilobol were therefore performed. In experiment I, mice received a single application of 2.5, 50 or 1000 micrograms of bilobol, or 0.1 or 2.5 micrograms of TPA on the right ear. The 50 or 1000 micrograms bilobol and 2.5 micrograms TPA doses caused ear redness, epidermal thickening and inflammatory infiltration. The dose of 2.5 micrograms of TPA, which is usually used as tumor promoter in skin carcinogenesis, was equivalent to 50 micrograms of bilobol in irritant effect. Thus, 50 micrograms of bilobol was used for the promotion testing (experiment II) in CD-1 mice initiated with 100 micrograms of 7, 12 dimethylbenz[a]anthracene (DMBA). Treatment with either 10 or 50 micrograms bilobol twice a week for 30 weeks did not result in any tumor development, thus suggesting that bilobol is not a complete promoter of skin carcinogenesis, despite generation of inflammation. PMID- 2110597 TI - Coronary thrombolysis and gender. PMID- 2110596 TI - Activation of a beta-galactosidase recombinant provirus: application to titration of human immunodeficiency virus (HIV) and HIV-infected cells. AB - A quantitative bioassay for human immunodeficiency viruses has been developed on the basis of the ability of the tat gene to transactivate the expression of an integrated beta-galactosidase gene in a HeLa-CD4+ cell line. Infection by a single virion of HIV-1 or HIV-2 corresponds to a unique blue syncytium or a cell cluster detected after fixation and addition of 5-bromo-4-chloro-3-indolyl-beta-D galactopyranoside (a beta-galactosidase substrate). The number of infected lymphoid cells in a culture (stimulated human peripheral blood lymphocytes and cell lines) can also be quantified by cell-to-cell transmission of HIV into the HeLa-CD4(+)-beta-galactosidase monolayer. Infections by simian immunodeficiency viruses are similarly detected. This assay has been used to determine the dose response of drugs, the half-life of HIV at 37 degrees C, and the appearance of infectious particles after virus infection. PMID- 2110598 TI - [Acute ulceration of the gastroduodenal mucosa (review of the literature)]. PMID- 2110600 TI - [Intravenous infusions of nitroglycerin in unstable stenocardia]. AB - Clinical and prognostic significance of intravenous nitroglycerin infusions (INI) were studied in 127 patients with unstable angina pectoris. INI dose ranged from 25 to 800 micrograms/min (mean 198.2 +/- 21.8 micrograms/min), the duration varied from 2 h to 20 days (mean 5.2 days). Unfavorable effects occurred in 50 patients (39.3%): 18 patients developed myocardial infarction which was fatal in 10 cases, one died of circulatory insufficiency, transluminal angioplasty was performed in 6, aortocoronary shunting in 26. INI promoted stabilization of the disease in 77 patients (60.7%). They were discharged from the hospital to continue on maintenance therapy. PMID- 2110599 TI - [Normoglycemia as a therapy goal in diabetes treatment--concept and realization]. AB - In diabetic patients (near-)normoglycemic control of blood glucose can only rarely be achieved by conventional insulin treatment. Novel strategies for this goal include transplantation of pancreatic tissue (whole organ, segment or isolated islets), the artificial pancreas with continuous blood glucose monitoring, insulin pump treatment and the intensified conventional treatment both of the latter including self-measurement of blood glucose and self adaptation of the insulin dosis. The results of pancreas transplantation in recent years have shown a marked improvement, the one-year survival rate of a functioning organ is in the range of 50-70%. Due to the lifelong immunosuppression pancreas transplantation should be considered in diabetic patients who need a kidney transplantation and for this reason already require immunosuppression. In spite of encouraging results in animals islet transplantation in humans has been disappointing to date. The artificial pancreas at present cannot be used for long-term treatment mainly due to the problems of the glucose sensor. The application of insulin pump treatment without continuous monitoring of blood glucose (open loop) and intensified conventional treatment both can lead to improved glycemic control in spite of a more flexible life style. Only this way of treatment made it possible to perform randomized prospective studies in diabetic patients on the effect of (near-)normoglycemic control on secondary complications. The first results show a tendency towards a positive effect on mild to moderate diabetic retinopathy over 2 years. Thus, every juvenile diabetic patient should be informed about these possibilities of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110601 TI - Increased sensitization to aeroallergens in competitive swimmers. AB - Chlorine is used to disinfect swimming pools or as a constituent of other disinfection reagents. Pulmonary diseases are occasionally observed after exposure to chlorine. In 14 competitive swimmers and in 14 matched control subjects, we searched for clinically manifest allergies, subclinical sensitization to aeroallergens, imbalance of the cellular immune system, and bronchial hyperresponsiveness. Conjunctival or respiratory symptoms were found in 11 swimmers (2 cases of conjunctivitis, 4 rhinitis, 2 rhinoconjunctivitis, 1 laryngitis, and 2 bronchitis) and in 3 controls. Sensitization to aeroallergens was confirmed in 9 swimmers by skin test and in 11 swimmers by radioallergosorbent test (RAST), compared to findings in 4 and 5 controls, respectively. An altered cellular immune system, (i.e., imbalance in T-cell system, B-cell system, or natural killer cells) was detected in 7 swimmers and only 2 controls. Bronchial hyperresponsiveness to methacholine was seen in 11 swimmers and 5 controls. This higher incidence of allergic diseases and subclinical sensitization to aeroallergens, disorders of the cellular immune system, and bronchial hyperresponsiveness in competitive swimmers compared with control subjects could be due to repeated exposure to chlorine in swimming pools. PMID- 2110602 TI - What is sarcoidosis? PMID- 2110604 TI - Predictive value of the single-breath nitrogen test for hospitalization due to respiratory disease. AB - The relationship between indices of the single-breath nitrogen test (SBNT) measured in 1974 and hospitalization in the 9 year period 1977-1986 was examined in a random population sample of 876 men aged 46-69 years. Men who could not perform acceptable SBNT tracings had an increased risk of hospitalization due to respiratory disease in general. When age and smoking habits were controlled for, slope of phase III was significantly related to hospitalization due to respiratory disease in general and chronic obstructive pulmonary disease (COPD), whereas closing volume and closing capacity were marginally related to hospitalization due to respiratory disease in general but not to hospitalization due to COPD. The relationship between slope of phase III and hospitalization due to COPD remained significant after the forced expiratory volume in 1 sec (FEV1) was controlled for: odds ratio 1.4 per % N2/L (95% confidence interval 1.1-1.7). The effect of the slope of phase III was considered to be clinically insignificant, and we conclude that in a random population sample indices from only 1 SBNT do not provide prognostic information concerning hospitalization in addition to that provided by FEV1. PMID- 2110603 TI - Antigen-induced T-cell changes: modulation by pharmacologic agents. AB - To determine the effect of pharmacologic modulation of alterations of peripheral blood T-cell subsets caused by antigen-induced bronchoconstriction, we administered albuterol immediately after antigen-induced bronchoconstriction in a double-blind to protocol to 12 atopic asthmatic subjects. We also administered cromolyn sodium before antigen to 7 of the same subjects. Peripheral blood T-cell subset composition (CD4, CD8, Ia) of a highly purified T-cell preparation was determined before, 24, 48, 72, and 168 h after bronchoconstriction. We found that placebo inhalation immediately after antigen-induced bronchoconstriction did not affect subsequent peripheral blood T-cell subset changes (decrease in CD4+ and increase in Ia+ T lymphocytes). In contrast, inhaled albuterol abolished these T cell subset changes. Although cromolyn sodium significantly decreased the severity of antigen-induced bronchoconstriction, it did not affect T-cell subset composition changes at the dosage used. We conclude that albuterol can ablate T cell subset changes associated with antigen-induced bronchoconstriction. Cromolyn sodium ameliorates bronchoconstriction, but has no affect on T-cell subset composition changes. This implies that T-cell changes and bronchoconstriction caused by antigen inhalation are mediated through different pathways. PMID- 2110605 TI - [Gamma interferon and adenosine deaminase in pleuritis]. AB - The concentration of gamma interferon (IFN gamma) and adenosine deaminase (ADA) activity were measured in the pleural fluid of 162 patients to compare their diagnostic significance and to establish a possible correlation between both tests. The IFN gamma levels in tuberculous pleural effusions were quite variable, with a mean of 93 U/ml and a median of 48 U/ml. They were higher than 2 U/ml in all cases, whereas no case of nontuberculous effusion showed higher values. ADA activity was higher than 43 U/l in all tuberculous effusions, with a mean value of 80 U/l, higher than in any other group except lymphoma. In three pleural effusions associated with lymphoma, one with mesothelioma, one with adenocarcinoma and four with empyema, ADA activity was higher than 43 U/l. In these patients, IFN gamma levels were low. There was no correlation in the whole series or in any group between IFN and ADA. Both parameters can be very useful for the diagnosis of tuberculous pleuritis. The measurement of IFN gamma is more specific, although the experience with this test is more limited than with ADA. It has the additional shortcoming of a high cost and it requires facilities for radionuclide use. Therefore, we think that ADA measurement should be considered as a routine test while IFN gamma measurement should be reserved for reference institutions. PMID- 2110606 TI - [Experience in the use of subtotal irradiation at different stages of therapy in lymphogranulomatosis]. AB - A study was made of a possibility to use subtotal irradiation (STI) as an equivalent of chemotherapy for the treatment of 33 Hodgkin's disease patients aged 17 to 77 (of them 25 were treated during the 1st-19th yrs. of therapy, for 8 patients it was the 1st stage of antitumor therapy). ROKUS apparatus and a linear accelerator of 15 MeV were used for irradiation at a single dose of 1.5 Gy and a total dose of 3-6 Gy, at a 2-4 day interval. STI efficacy was assessed by a response of the peripheral and intrathoracic lymph nodes, tumor foci in the lungs, by a decrease in liver and spleen sizes, a decrease in body temperature and the end of night sweating. Of 25 patients a positive effect was achieved in 19, in 4 patients it was absent, and in 2 patients disease progression was observed. A marked positive effect was noted in 8 previously untreated patients, especially with respect to the elimination of signs of intoxication. A conclusion has been made that STI can be employed for the treatment of Hodgkin's disease patients as a method of general cytostatic action. STI causes a more noticeable and prolonged leukopenia than a cycle of polychemotherapy. PMID- 2110607 TI - Glucose metabolism and colorectal carcinoma. AB - We evaluated nine patients with colorectal cancer and six control patients in a postabsorptive state in an attempt to define the effect of cancer on glucose turnover, oxidation, recycling, and resting metabolic expenditures (RME). The glucose kinetics were determined using a double-labeled [U-14C] glucose and [6 3H] glucose, and energy expenditures were measured by indirect calorimetry. In addition, we also measured the same parameters in the cancer patient group on a total parenteral nutrition (TPN)-glucose system on the fourth day before and on the fifth day after removal of tumor. In the postabsorptive state, glucose turnover and oxidation rates were similar in the cancer and control group; however, the mean glucose pool size of the cancer group was 47% larger than the control group and was statistically significant (P = .05). Glucose recycling was also two times the control group and was statistically significant (P = .05). The recycling of glucose, both preoperatively and postoperatively, continued in the face of infused glucose; however, the rate was suppressed compared with the fasting cancer group. Postabsorptive RME of the cancer group did not differ from those predicted by the Harris-Benedict equation. Following a 4-day infusion of TPN-glucose that supplied a mean of two times the patients' energy needs, the preoperative cancer group showed a mean increase in RME of 25.6% and a 31.58% increase on the fifth postoperative day of TPN-glucose, presumably due to increased lipogenesis and to a much lesser extent from the increased protein synthesis (4 g positive N balance).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110608 TI - Decreased glucose oxidation during short-term starvation. AB - Prolonged fasting (for days or weeks) decreases glucose production and oxidation. The effects of short-term starvation (ie, less than 24 hours) on glucose metabolism are not known. To evaluate this issue, glucose oxidation and glucose turnover were measured after 16-hour and subsequently after 22-hour fasting. Glucose oxidation was calculated by indirect calorimetry in 12 healthy men (age 22 to 44 years); glucose turnover was measured by primed, continuous infusion of 3-3H-glucose in eight of these 12 volunteers. After 16-hour fasting net glucose oxidation was 0.59 +/- 0.17 mg x kg-1 x min-1 and glucose tissue uptake 2.34 +/- 0.12 mg x kg-1 x min-1. No correlation was found between net glucose oxidation and glucose tissue uptake. Prolonging fasting with an additional 6 hours resulted in decreases of respiratory quotient (0.77 +/- 0.01 v 0.72 +/- 0.01) (P less than .005), plasma glucose concentration (4.7 +/- 0.1 v 4.6 +/- 0.1 mmol/L) (P less than .05), glucose tissue uptake (2.10 +/- 0.12 mg x kg-1 x min-1) (P less than .05), net glucose oxidation (0.09 +/- 0.04 mg x kg-1 x min-1) (P less than .005), and plasma insulin concentration (8 +/- 1 v6 +/- 1 mU/L) (P less than .005). Net glucose oxidation expressed as a percentage of glucose tissue uptake decreased from 22% +/- 8% to 2% +/- 1% (P less than .05). There was no net glucose oxidation in seven of 12 controls after 22-hour fasting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110609 TI - Metabolic regulation of apoproteins of high-density lipoproteins by estrogen and progesterone in the baboon (Papio sp). AB - To determine the metabolic regulation of the apoproteins of high-density lipoproteins (HDL) by estrogen and progesterone, 12 ovariectomized and hysterectomized baboons were fed a high cholesterol, high fat diet and were divided into four groups. One of these groups was the untreated control and the remaining three groups were treated with estrogen, progesterone, or a combination of both. After 10 months of treatment, there were significant differences in HDL apolipoprotein (apo) A-I and apo A-II levels in these groups. The apo A-I level was highest in baboons treated with the combination therapy, followed by those treated with estrogen. Baboons treated with progesterone and those in the control group had similar levels of apo A-I. Baboons treated with both estrogen and progesterone and estrogen alone had significantly higher levels of apo A-I than those in the control or progesterone group. Baboons treated with hormones had higher apo A-II levels than controls, and those treated with the combination therapy had the highest level. Metabolic studies suggested that both estrogen and progesterone increased apo A-I and apo A-II production. Progesterone also increased the fractional catabolic rate of apo A-I, but not of apo A-II. On the other hand, estrogen did not affect the fractional catabolic rate of either apo A I or apo A-II. Thus, increased apo A-I content of HDL in baboons treated with both estrogen and progesterone or estrogen alone appears to be due to increased apo A-I synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110610 TI - Antibiotic activity of natural products: 1. Propolis. AB - Material extracted from propolis (bee glue) by alkaline aqueous solvents or organic solvents showed weak inhibitory activity in vitro against certain species of Gram-positive bacteria. No antimicrobial activity was detected in urine from three volunteers who had taken 500 mg propolis three times a day for 3 days. PMID- 2110611 TI - Genetic transformation and cell morphology of Bacillus subtilis grown in Mg+(+) limited chemostat culture. AB - The rate and frequency of genetic transformation of Bacillus subtilis grown in Mg+(+)-limited chemostat culture are dependent on the dilution rate (D) of the system and achieved maximum values at D = 0.23 h-1. Mg+(+)-limitation induced a morphological change in the cells from their normal rod shape to extended helices. Although this change in shape was a transient phenomenon, under some conditions it persisted for several days and resulted in an apparent increase in the transformation frequency. PMID- 2110612 TI - Evidence for the involvement of thiocyanate in the inhibition of Candida albicans by Lactobacillus acidophilus. AB - Lactobacillus acidophilus has been found to inhibit Candida albicans when grown on MRS agar plates. Attempts to isolate an active factor responsible for this inhibition from liquid culture and agar plates were not successful. The addition of sodium thiocyanate to the agar was found to increase the inhibition offered by the lactobacillus. The results indicate that hydrogen peroxide produced by the lactobacillus is being used to convert the thiocyanate to hypothiocyanate which is more toxic. The involvement of a lactobacillus peroxidase in this conversion is postulated. PMID- 2110613 TI - [Hypoglycemia in type II diabetic patients]. AB - The incidence of hypoglycemia was determined in 138 type-2 diabetics treated with insulin (40%) or sulfonylureas (60%). Within one year, ten patients (7%) experienced one severe hypoglycemic episode characterized by a loss of consciousness and the necessity of parenteral glucose administration. Insulin treatment and advanced age increased the risk of hypoglycemia. The knowledge about hypoglycemia was poor. Only 45% of the patients could give a correct definition, 18% knew more than two symptoms, and 15% knew at least one cause of hypoglycemia. 66% would treat hypoglycemia with oral carbohydrates. The risk of hypoglycemia should be considered in the planning of adopted teaching and treatment programs for patients with type-2 diabetes. PMID- 2110614 TI - [Pseudohypoparathyroidism: a rare, ambiguous "seizure disorder"]. PMID- 2110615 TI - [Possible use of recombinant CD4 in the therapy of AIDS]. PMID- 2110616 TI - Accountability, affordability, and quality health care. Mutual responsibilities for the 1990s. PMID- 2110617 TI - Injuries associated with horseback riding--United States, 1987 and 1988. PMID- 2110618 TI - Alcohol use and aquatic activities--Massachusetts, 1988. PMID- 2110619 TI - Aeromonas wound infections associated with outdoor activities--California. PMID- 2110620 TI - Malignant melanoma of the skin--New Jersey, 1979-1985. PMID- 2110621 TI - Swimming-associated cryptosporidiosis--Los Angeles County. PMID- 2110622 TI - Different effect of hyperthermia and heat shock on the action of quinolone drugs versus some mutagens against chloroplasts of Euglena gracilis. AB - Hyperthermia (37 degrees C permanently) and heat shock (42 degrees C for 10 min, and then 27 degrees C) retarded the elimination of chloroplasts from the flagellate Euglena gracilis induced by quinolone antibacterial chemotherapeutics (OA, NA, Cnx, Ofx, Cpfx, Enx, Nfx) in comparison with their action at 27 degrees C. In the case of OA, NA, and Cnx those hyperthermic conditions completely blocked their action against chloroplasts. On the other hand, both temperature regimes accelerated the antichloroplast activity of the mutagens/carcinogens nitrosoguanidine and furylfuramide. PMID- 2110623 TI - In vivo anticlastogenic and antimutagenic effects of tannic acid in mice. AB - The anticlastogenic effect of tannic acid was studied in vivo in the mouse micronucleus test. The frequencies of micronuclei induced by mitomycin C, ethyl nitrosourea (ENU) or 4-nitroquinoline 1-oxide in mouse bone marrow cells were decreased by the oral administration of tannic acid 6 h before the mutagen injection. The observed suppressing effect was not a reflection of a delay in the formation of micronuclei by the cytotoxic effect of tannic acid. The antimutagenic effect of tannic acid was also investigated in vivo in the mouse spot test using male PW and female C57BL/10 mice. Tannic acid was given orally to pregnant females 6 h before the intraperitoneal injection of ENU on the 10th day of pregnancy. The frequency of pups with recessive color spots induced by ENU was decreased by the administration of tannic acid. The observed decrease was not due to toxic effects on the embryo. These results indicate that tannic acid acts as an anticlastogen and antimutagen in vivo. PMID- 2110624 TI - Deprenyl for the treatment of early Parkinson's disease. PMID- 2110625 TI - Inhibition of mutant troponin C activity by an intra-domain disulphide bond. AB - Triggering of contraction in striated muscles involves a conformational transition in the N-terminal domain of troponin C, the calcium-binding component of thin filaments. We have designed a mutant troponin C in which the key conformational transition and the calcium-regulatory activity are reversibly blocked by the formation of a disulphide bridge. Our results may be applicable to other proteins of the same family of calcium-binding proteins. PMID- 2110626 TI - Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. AB - Studies of cultured bovine aortic endothelial cells using quantitative chemiluminescence techniques have shown that the amount of nitric oxide released under basal conditions, or in response to either bradykinin or the calcium ionophore A23187 is insufficient to account for the vasorelaxant activities of the endothelium-derived relaxing factor (EDRF) derived from the same source. This observation contradicts previous suggestions that nitric oxide and EDRF are the same compound, but may be explained if EDRF is a compound that contains nitric oxide within its structure but is a much more potent vasodilator than nitric oxide. Such a molecule could be one of several nitrosothiols which may yield nitric oxide after a one-electron reduction. The present experiments were carried out to test the possibility that the biological activities of the endothelium derived relaxing factor might more closely resemble those of one of these compounds, S-nitrosocysteine, than nitric oxide. Nitric oxide release from cultured bovine aortic endothelial cells was detected by chemiluminescence and bioassay experiments compared the vasodilator potencies of nitric oxide, S nitrosocysteine, and EDRF. The results suggest that EDRF is much more likely to be a nitrosylated compound such as a nitrosothiol than authentic nitric oxide. PMID- 2110627 TI - Cryopreservation of Drosophila melanogaster embryos. AB - There is an urgent need to preserve the ever-increasing number (greater than 30,000) of different genetic strains of D. melanogaster that are maintained in national and international stock centres and in the laboratories of individual investigators. In all cases, the stocks are maintained as adult populations and require transfer to fresh medium every two to four weeks. This is not only costly in terms of materials, labour and space, but unique strains are vulnerable to accidental loss, contamination, and changes in genotype that can occur during continuous culture through mutation, genetic drift or selection. Although cryopreservation of Drosophila germ-plasm would be an enormous advantage, many attempts using conventional procedures have been unsuccessful. D. melanogaster embryos are refractory to conventional cryopreservation procedures because of the contravening conditions required to minimize mortality resulting from both intracellular ice formation and chilling injury at subzero temperatures. To overcome these obstacles, we have developed a vitrification procedure that precludes intracellular ice formation so that the embryos can be cooled and warmed at ultra-rapid rates to minimize chilling injury, and have recovered viable embryos following storage in liquid nitrogen. In a series of 53 experiments, a total of 3,711 larvae emerged from 17,280 eggs that were cooled in liquid nitrogen (18.4 +/- 8.8%). Further, using a subset from this population, approximately 3% of the surviving larvae (24/800) developed into adults. These adults were fertile and produced an F1 generation. PMID- 2110628 TI - Bacillus subtilis expressing a haemolysin gene from Listeria monocytogenes can grow in mammalian cells. AB - Intracellular parasites can be classified into those that reside within a host vacuole and those which grow directly in the host cytoplasm. Members of the latter group, which includes Rickettsia, Shigellae, Trypanosoma cruzi, and Listeria monocytogenes, possess haemolytic activity associated with the ability to enter the host cytoplasm. Therefore mutants of L. monocytogenes lacking a pore forming haemolysin, listeriolysin O, do not escape from the endosomal compartment and consequently fail to become established in the cytoplasm. To examine the role of listeriolysin O, we cloned the structural gene for the L. monocytogenes haemolysin, hlyA, into an asporogenic mutant of Bacillus subtilis under the control of an IPTG-inducible promoter. After being internalized by the macrophage like cell line J774, haemolytic B. subtilis disrupted the phagosomal membrane and grew rapidly within the macrophage cytoplasm. These results show that a single gene product is sufficient to convert a common soil bacterium into a parasite that can grow in the cytoplasm of a mammalian cell. PMID- 2110629 TI - [Aldose reductase inhibitors in diabetic neuropathy]. PMID- 2110630 TI - [Breast cancer in The Netherlands]. PMID- 2110631 TI - Dementia--quality health care and cost effectiveness of evaluation. PMID- 2110632 TI - [Role of parenteral feeding in an operative protocol of total artificial nutrition]. AB - Two cases of enterocutaneous fistula treated with mixed artificial diet (NP + NE) where enteral nutrition played the principal role in weaning from i.v. nutrition have been examined. Gradual transit was possible to normal diet, demonstrating ease of use and effectiveness of the nutritional contribution. PMID- 2110633 TI - Inactivation of a slow Ca2+ current in CA1 neurones of the adult rat hippocampal slice. AB - CA1 neurones of the adult rat hippocampal slice preparation were voltage clamped at or near -40 mV membrane potential using a single electrode clamp method. Depolarizing voltage commands from a holding potential of -40 mV elicited voltage dependent inward Ca2+ currents comprising a fast and a slow component. The latter one was investigated for its susceptibility to inactivation, which was maximally expressed at around 0 mV membrane potential. When extracellular Ca2+ was replaced by Ba2+, inward currents became much larger and were followed by long tail currents. Similar data were observed in neurones injected with the Ca2+ chelator BAPTA. It is suggested that inactivation of the slow Ca2+ current depends at least partly on the levels of intracellular free Ca2+ in hippocampal neurones. PMID- 2110634 TI - A comparison of preparation-related neuronal activity changes in the prefrontal, premotor, primary motor and posterior parietal areas of the monkey cortex: preliminary results. AB - Single-unit activity of prefrontal (PF), premotor (PM), primary motor (MI) and posterior parietal (PP) cortical areas was analysed from 3 monkeys trained to perform visually guided arm movements in a between-arms choice reaction time (RT) task. Percentages of preparation-related units, i.e. units whose change in activity during the preparatory period was correlated with RT, were 19% in PF, 31% in MI, 46% in PM and 68% in PP, respectively. These data support the hypothesis that neural pathways connecting PP association areas to MI, via PM, are involved mainly in movement planning. PMID- 2110635 TI - MK-801 induces c-fos protein in thalamic and neocortical neurons of rat brain. AB - MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, leads to a dramatic induction of c-fos-like protein in neurons in deep layers of the neocortex, in dorsal and ventral midline thalamic nuclei and in neurons in the central grey of rat brain. This induction of c-fos by MK-801 is dose-and time dependent occurring within 2 h and dissipating by 24 h after injection (0.5-8.0 mg/kg, i.p.). The mechanism of this paradoxical induction of c-fos by MK-801 is unclear; however, the pattern of induction appears to follow the distribution of the antagonist-preferring NMDA receptor site. PMID- 2110636 TI - Opiates modify induction of c-fos proto-oncogene in the spinal cord of the rat following noxious stimulation. AB - The expression of the proto-oncogene c-fos in neurons of the spinal cord dorsal horn of the rat following noxious thermal stimulation was compared in morphine- and ketamine-treated animals. Intravenous injection of morphine reduced the number of c-fos-positive neurons by up to 85% in laminae III-VI and X. This effect was dose dependent and naloxone reversible. The non-competitive N-methyl-D aspartate (NMDA) antagonist ketamine had no effect. The present data show that morphine suppresses the induction of c-fos. A block of Ca2+ influx through voltage- and ligand (NMDA)-gated channels does not influence c-fos protein synthesis in the dorsal horn of the spinal cord in vivo. PMID- 2110637 TI - Antidepressants induce regeneration of catecholaminergic axon terminals in the rat cerebral cortex. AB - Although repeated but not single administration of antidepressants exerts therapeutic effect on clinical depression, the mechanism of the clinical efficacy of antidepressants remains unknown. This report shows a novel action of antidepressants which can explain the delayed onset of clinical action of the drugs. Continuous infusion of the antidepressants maprotiline or desipramine into the rat cerebral cortex pretreated with the catecholamine neurotoxin 6 hydroxydopamine induced regeneration of noradrenergic axon terminals. This finding provides evidence that antidepressants possess the ability to cause axonal sprouting of central noradrenergic (and possibly dopaminergic) neurons in the mature brain. PMID- 2110638 TI - Beta-alanine potentiation of [3H]flunitrazepam binding to rat spinal cord homogenates. AB - The effect of beta-alanine, gamma-aminobutyric acid (GABA), and other functionally related amino acids on [3H]flunitrazepam binding to rat spinal cord homogenates was studied. beta-Alanine potentiated [3H]flunitrazepam binding by 40% and GABA by 88%. Taurine increased the binding by 19%. Hypotaurine produced an 11% increase. No significant effect was seen in glycine, alanine, serine, valine or the dipeptide carnosine. The beta-alanine increase in [3H]flunitrazepam binding was completely inhibited by 10 microM strychnine, whereas the GABA increase required 0.1 mM strychnine to be fully suppressed. Results suggest that beta-alanine specifically potentiates binding of [3H]flunitrazepam in rat spinal cord homogenates. PMID- 2110639 TI - Effect of excitatory amino acids on microtubule-associated proteins in cultured cortical and spinal neurones. AB - The effect of excitatory amino acid stimulation on the cytoskeleton of cultured spinal cord and cortical neurons was monitored with antibodies against microtubule-associated proteins tau and MAP2. In unstimulated cultures tau-1 immunoreactivity was restricted to axon-like processes. Stimulation with glutamate (0.1-1 mM) or N-methyl-D-aspartate (NMDA) (0.1 mM) resulted in a dramatic increase in the intensity of tau labelling in axons and the appearance of staining within a proportion of neuronal cell bodies and dendrites. Quisqualate or kainate stimulation resulted only in an increase in tau immunoreactivity within axons. The NMDA mediated events were calcium dependent and the effects of all excitatory amino acids could be blocked by specific antagonists. In contrast, following stimulation with excitatory amino acids, MAP2 immunoreactivity was associated with filaments which formed a complex network within the cell body. This suggests that the different excitatory amino acid receptor subtypes can have differential effects on the neuronal cytoskeleton. PMID- 2110640 TI - Cost accountability and clinical nurse specialist evaluation. PMID- 2110641 TI - Work-site health promotion programs need analysis of cost-effectiveness. PMID- 2110642 TI - Bacterial adherence to extended wear soft contact lenses. AB - The authors studied the adherence of Pseudomonas aeruginosa and Staphylococcus aureus to extended wear soft contact lenses (EWSCLs) with and without focal deposits using both a radiolabeling technique and electron microscopy. P. aeruginosa showed significant adherence to contact lenses in vitro. In contrast, S. aureus failed to show significant adherence to contact lenses in vitro (i.e., the radioactive uptake was not significantly above background). The extent of adherence of Pseudomonas was proportional to the number of focal deposits on the lenses. Results of electron microscopic examination showed the bacteria to be adherent primarily to large focal deposits (greater than or equal to 150 microns). There was no pseudomonal adherence to the small focal deposits (less than or equal to 50 microns) and little adherence to the areas in between the focal deposits. The authors hypothesize that worn lenses, especially those with large focal deposits, serve as a vehicle for the transport of P. aeruginosa to the cornea. This hypothesis could be a partial explanation for the high incidence of keratitis caused by P. aeruginosa in EWSCL patients. PMID- 2110643 TI - Diagnosis and management of the thyroid nodule. An overview. AB - The traditional approach to evaluation of patients with thyroid nodules is being replaced by more cost-effective methods of diagnosis. The author describes a rational approach to the evaluation of thyroid nodules that takes into consideration patient factors, minimizes false-positive diagnoses of cancer, and balances the competing responsibilities of cost-effective management and identifying all patients with thyroid carcinoma. PMID- 2110644 TI - Hyperparathyroidism. AB - Primary hyperparathyroidism can be caused by a solitary parathyroid adenoma and sometimes by hyperplastic parathyroid glands, multiple adenomas, or carcinoma. In the majority of patients, the diagnosis is made tentatively by chemistry profiles that show elevated serum calcium. It is confirmed by repeated serum calcium values and PTH determination. The parathyroid abnormality, if an adenoma, can usually be localized preoperatively by thallium-technetium scan, ultrasound, or computed tomography. In the case of persistent disease with hypercalcemia, an angiogram with selective venous sampling for PTH is helpful. At exploration, both sides of the neck may need exploration. A unilateral procedure may be sufficient, if the preoperative localization tests are confirmatory and if biopsy of another "normal" gland shows normal histologic findings. During the postoperative period, suction drains will lessen the likelihood of hematoma formation and serum calcium levels are monitored for the first 3 to 5 days. Symptomatic patients with low calcium levels receive intravenous and oral calcium supplements until values are brought to the low-normal range. Supplements are tapered as the calcium in the serum rises. The majority of patients who undergo parathyroid surgery will benefit both symptomatically and metabolically. PMID- 2110645 TI - [Primates in the study of oocyte maturation]. AB - In the mammalian oocyte, meiosis is initiated during fetal life. Meiosis proceeds up to the diplotene stage of the first prophase and is arrested at birth and the oocyte presents a nuclear structure known as germinal vesicle (GV). Meiotic arrest persists until sexual maturity, when one or more oocytes, the number dependent on the species, reinitiate their reduction division at each cycle. The series of event, initiated by the breakdown of the germinal vesicle (GVBD) and completed with formation of the polar body, leads to the production of a mature, fertilizable oocyte, and is defined as oocyte maturation. Maturation of the oocyte is an essential prelude to fertilization. Normally the meiosis is reinitiated by the preovulatory LH peak but when meiotically arrested oocytes are removed from the antral follicles, they resume meiosis spontaneously in vitro. However primate (human and monkeys) oocytes isolated from antral follicles and cultured within their cumuli for two days, spontaneously resumed meiosis at a very low rate (less than 30%) compared to other mammals. Cynomolgus monkey oocyte then appears as a good model for in vitro studies of maturation initiation. Follicular atresia improve significantly the GVBD rate (about 50%). The cumulus cell mass takes an important part in the maintenance of the meiotic arrest since its mechanical removal is followed by an increase of the GVBD (P less than 0.02). A gonadotropin releasing hormone agonist (GnRHa) and a protein kinase C activator added to the culture medium both improve the GVBD (54% and 55% respectively, P less than 0.01). The GnRHa oocyte maturation induction is probably protein kinase C dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110646 TI - [Primates in the study of hepatitis viruses]. AB - There is no a conventional tissue culture system for the propagation of the hepatitis viruses and only some of them can be maintain in continuous cell culture in particular conditions. A transmissibility of hepatitis is limited to primates. The narrow host specificity may help to establish the classification of the hepatitis viruses and their mode of transmission. Moreover, the primate animal model provided the most accessible source of viruses and for clinical reasons presents the only opportunity for the studies of pathogenic mechanisms involving cellular immunity with allogenic restriction. The marmosets and chimpanzees susceptible to the hepatitis A and B viruses, respectively are the primates of choice for the experimental models. For the studies on parenterally transmitted NANB hepatitis the chimpanzee and some rhesus monkeys may provide an animal system. At last, most of the primates seem to be susceptible to agent responsible for the water-borne non A non B hepatitis. PMID- 2110647 TI - [Primates as a model for the study of lentiviruses and AIDS]. AB - Neither vaccine nor therapy are, to date, available against human HIV infections. Because few is known on human pathogenesis, a standardized animal model is urgently required. Today, different models have been available: 1) "partial models" of the human infection (murine retrovirus, infection of SCID or transgenic mice with HIV, sheep infection with Visna, rabbits infected with HIV1, etc.). These models cannot be used in testing vaccine strategies, but may help in evaluating some particular stages of the pathogenesis of the disease, and the targets of antiretroviral drugs. 2) Disease models, such as cats infected with FIV, and, above, primates infected with HIV or SIV (SIV infected macaques, and, perhaps, HIV2 rhesus monkeys). Primate models are the only possibility to day in testing vaccine procedures before screening among a large population of seronegative humans, and determining drug combination which might be useful in HIV specific therapy. The best primate model is today the SIVMAC251 infected rhesus monkey model, which standardization is now on progress. PMID- 2110648 TI - [The marmoset in biomedical research. Value of this primate model for cardiovascular studies]. AB - Because of its small size, low cost of maintenance, breeding capabilities in captivity, the marmoset, a New World monkey, appears well suited for clinical and fundamental investigations. The contribution of this laboratory animal in the main areas of biomedical research is succinctly described: viral oncology, infections diseases, immunology, reproduction, toxicology and teratology, odontology, behaviour and neuro-psychopathology. Emphasis is put upon the exceptional interest of the use of marmoset as a biological model in cardiovascular studies. PMID- 2110649 TI - Congenital tuberculosis, still a problem. PMID- 2110650 TI - Genital mycoplasmas and the pediatrician. PMID- 2110651 TI - Cost-benefit analysis of Haemophilus influenzae type b prevention: conjugate vaccination at eighteen months of age. AB - A cost-benefit analysis of Haemophilus influenzae type b disease preventive strategies was updated to consider evaluation of the H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) and H. influenzae type b oligosaccharide-mutant diphtheria toxin conjugate vaccine (HbOC) for children at 18 months of age. The analysis was done from the perspective of society as a whole. The economic costs of H. influenzae type b disease in the 1988 United States birth cohort would be $2.546 billion (1988 U.S. dollars) in the absence of preventive efforts. If 60% of all children could be vaccinated with PRP-D or HbOC at 18 months of age, this strategy would save $207.1 million ($88.22 savings/vaccinee; $43,605 cost/case prevented; 3.57/1 benefit-to-cost ratio) under base case model assumptions. Universal PRP-D or HbOC vaccination at 18 months of age would prevent 1845 cases of invasive H. influenzae type b disease. The break-even efficacy for universal PRP-D or HbOC vaccination at 18 months of age was 22.7%. We conclude that, under the model base case assumptions, universal PRP-D or HbOC vaccination at 18 months of age is sufficiently efficacious so that the costs of vaccination would be more than offset by decreased medical care costs for treating H. influenzae type b disease. PMID- 2110652 TI - Helicobacter pylori in gastroduodenal disease. AB - Helicobacter pylori is a recently described Gram-negative micro-organism, which plays an important role in the pathogenesis of peptic ulcer disease and gastritis. In this paper an outline is given of the history and the pathophysiology of Helicobacter pylori, as well as the therapeutic studies aimed at eradication of the bacterium in various clinical entities. PMID- 2110653 TI - Characterization of the v-myb DNA binding domain. AB - The transforming protein encoded by the v-myb oncogene is a sequence-specific DNA binding protein that is thought to be involved in the regulation of gene expression. The N-terminal region of the v-myb protein is composed of two highly conserved tandem repeat sequences of unknown function. It has been speculated that the N-terminal v-myb repeats might be crucial for DNA-binding, since N terminal deletions destroy the DNA-binding activity of the v-myb protein. Here, we have studied the v-myb DNA-binding domain in more detail. Our results show that the N-terminal region of the v-myb protein is sufficient for specific DNA binding. Dissection of this region suggests that both repeats are required for DNA-binding, but that both repeats play different roles in v-myb protein DNA interaction. We also show that the myb repeats of a drosophila melanogaster homolog of c-myb function as sequence-specific DNA-binding domain. Our results support the view that specific sequence-recognition, mediated by the conserved myb repeats, is a general feature of myb-related proteins. PMID- 2110654 TI - The use of two-cistron constructions in improving the expression of a heterologous gene in E. coli. AB - Many heterologous genes when cloned into bacterial expression vectors are poorly expressed because of an inefficient ribosome binding site (RBS). We have constructed a plasmid which expresses human gamma-interferon (gamma-IF), where the level of expression is limited by the RBS. Expression was increased by placing the gamma-IF sequence immediately downstream of a small translated sequence. The production of gamma-IF was dependent upon the efficiency of translation of this upstream cistron and could be increased to very high levels. The same upstream cistron would greatly improve the expression of gamma-IF in a plasmid where the RBS was very poor due to inhibitory secondary structure at the 5' end of its mRNA. However, it would not improve the efficiency of a poor RBS containing a weak Shine-Dalgarno sequence. The general utility of the two-cistron expression strategy to diagnose a weak RBS is discussed. PMID- 2110655 TI - Properties of the transcriptional enhancer in Saccharomyces cerevisiae telomeres. AB - Saccharomyces cerevisiae chromosomes end with the sequence C2-3A(CA)1-4, commonly abbreviated as C1-3A. These sequences can function as upstream activators of transcription (UAS's) when placed in front of a CYC1-lacZ fusion gene. When C1-3A sequences are placed between the GAL1,10 UAS and the CYC1-lacZ fusion, the C1-3A UAS still functions and the amount of beta-galactosidase produced in cells grown on glucose is as much or more than that for cells grown on either glycerol medium, or cells grown on glucose medium containing a plasmid with just the C1-3A UAS. These data indicate that the UAS is immune from glucose repression from the upstream GAL1,10 UAS. Because C1-3A sequences are bound in vitro by the transcription factor RAP1, the UAS activity of yeast telomere sequences was compared with that of a similar UAS from the tightly regulated ribosomal protein gene RP39A, which also contains a RAP1 binding site. While transcription from the ribosomal protein gene UAS was responsive to cell density, the amount of transcription from the C1-3A UAS was nearly the same at all cell densities tested. These data show that the transcriptional activation by C1-3A sequences is not regulated by cell density. PMID- 2110656 TI - The Euglena gracilis chloroplast rpoB gene. Novel gene organization and transcription of the RNA polymerase subunit operon. AB - The rpoB gene coding for a beta-like subunit of the chloroplast DNA-dependent RNA polymerase has been located on the chloroplast genome of Euglena gracilis distal to the rrnC ribosomal RNA operon. We have determined 5760 base-pairs of DNA sequence, including 97 bp of the 5S rRNA gene, an intergenic spacer of 1264 bp, the rpoB gene of 4249 bp, 84 bp spacer and 67 bp of the rpoC1 gene. The rpoB gene is of the same polarity as the rRNA operons. The organization of the rpoB and rpoC genes resembles the E. coli rpoB-rpoC and higher plant chloroplast rpoB rpoC1-rpoC2 operons. The Euglena rpoB gene (1082 codons) encodes a polypeptide with a predicted molecular weight of 124,288. The rpoB gene is interrupted by seven Group III introns of 93, 95, 94, 99, 101, 110 and 99 bp respectively and a Group II intron of 309 bp. All other known rpoB genes lack introns. All the exon exon junctions were experimentally determined by cDNA cloning and sequencing or direct primer extension RNA sequencing. Transcripts from the rpoB locus were characterized by Northern hybridization. Fully-spliced, monocistronic rpoB mRNA, as well as rpoB-rpoC1 and rpoB1-rpoC1-rpoC2 mRNAs were identified. PMID- 2110657 TI - Nucleotide sequence of the erythromycin resistance gene from the Corynebacterium plasmid pNG2. PMID- 2110658 TI - Nucleotide sequence of a cDNA encoding a protein with primary structural similarity to G-protein coupled receptors. PMID- 2110659 TI - Nucleotide sequences of the variable regions of a mouse monoclonal antibody MRK16. PMID- 2110660 TI - Nucleotide sequence of a new BALB/c mouse kappa light chain variable region gene. PMID- 2110661 TI - Sequence variation in transcription factor IIIA. AB - Previous studies characterized macromolecular differences between Xenopus and Rana transcription factor IIIA (TFIIIA) (Gaskins et al., 1989, Nucl. Acids Res. 17, 781-794). In the present study, cDNAs for TFIIIA from Xenopus borealis and Rana catesbeiana (American bullfrog) were cloned and sequenced in order to gain molecular insight into the structure, function, and species variation of TFIIIA and the TFIIIA-type zinc finger. X. borealis and R. catesbeiana TFIIIAs have 339 and 335 amino acids respectively, 5 and 9 fewer than X. laevis TFIIIA. X. borealis TFIIIA exhibited 84% sequence homology (55 amino acid differences) with X. laevis TFIIIA and R. catesbeiana TFIIIA exhibited 63% homology (128 amino acid changes) with X. laevis TFIIIA. This sequence variation is not random; the C terminal halves of these TFIIIAs contain substantially more non-conservative changes than the N-terminal halves. In particular, the N-terminal region of TFIIIA (that region forming strong DNA contacts) is the most conserved and the C terminal tail (that region involved in transcription promotion) the most divergent. Hydropathy analyses of these sequences revealed zinc finger periodicity in the N-terminal halves, extreme hydrophilicity in the C-terminal halves, and a different C-terminal tail hydropathy for R. catesbeiana TFIIIA. Although considerable sequence variation exists in these TFIIIA zinc fingers, the Cys/His, Tyr/Phe and Leu residues are strictly conserved between X. laevis and X. borealis. Strict conservation of only the Cys/His motif is observed between X. laevis and R. catesbeiana TFIIIA. Overall, Cys/His zinc fingers in TFIIIA are much less conserved than Cys/Cys fingers in erythroid transcription factor (Eryf 1) and also less conserved than homeo box domains in segmentation genes. The collective evidence indicates that TFIIIA evolved from a common precursor containing up to 12 finger domains which subsequently evolved at different rates. PMID- 2110662 TI - Complete nucleotide sequence of the Bacillus subtilis dnaK gene. PMID- 2110663 TI - A novel allophycocyanin gene (apcD) from Cyanophora paradoxa cyanelles. PMID- 2110664 TI - Advances in venous access devices and nursing management strategies. AB - VADs are indicated for many persons who require reliable long-term venous access. Nontunneled, tunneled, and venous access ports are constructed of silicone or polyurethane, the most biocompatible materials identified thus far. These devices are inserted in a similar fashion and are extremely versatile. Although VADs represent a major advance in catheter technology, they are not without problems. The most serious and frequently reported complications include infection, thrombosis, and extravasation. Catheter occlusions are another frequent problem, and may be caused by clotted blood or precipitated drug within the catheter. Nursing care centers on prevention and intervention to remove the occlusion. Catheter-related infections may occur at one or more points along the catheter. The most serious are those occurring in the tunnel or as a result of a mural or catheter-tip thrombus. Normal skin flora are most commonly cultured with catheter related infections. These organisms may be introduced into the body through the catheter hub or less often by migrating along the external catheter. Infections differ in their severity, prognosis, and treatment. Actions to minimize risk (scrupulous care and patient teaching), prompt recognition, and appropriate interventions are crucial. Thrombotic events include fibrin sheaths, patchy thrombotic plaques on the cannulated venous intima, and totally occlusive mural thromboses. Problems associated with these can range from withdrawal occlusion to obstruction of the great vessels and symptoms of superior vena cava syndrome. Mural thrombosis, which probably occurs more frequently than previously suspected, is the most significant risk factor for infection and may also potentiate extravasation. Prompt initiation of therapy will resolve symptoms and maintain the functioning of the catheter. Extravasation can result in transient discomfort or major tissue damage, pain, and functional loss. Needle dislodgment from ports is the most frequent cause. Adequate stabilization of needles and use of nonsiliconized needles are recommended to decrease this risk. Thrombosis at the catheter tip with back tracking of infusate out of the vein to subcutaneous tissues is the second most frequent cause of extravasation and has been reported with tunneled catheters as well as ports. It should be noted that catheter-tip displacement and catheter damage infrequently lead to extravasation. When extravasation is suspected, the infusion is stopped, and the nurse notifies the physician so diagnostic procedures and treatment can be initiated. Other complications occur infrequently but may contribute to patient discomfort, morbidity, and mortality. These include phlebitis, which resolves with conservative management in most instances, and pneumothorax, which occurs in a small percentage of patients within a short period after catheter placement.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2110665 TI - Will healthcare be rationed? The 'future' is already here. PMID- 2110666 TI - Healthcare crisis. As I see it. What would you do to fix the healthcare system? PMID- 2110667 TI - [Characteristics of Mycobacteria from patients with genital tuberculosis]. AB - One hundred thirty six strains of Mycobacteria isolated from patients with genitalia tuberculosis were analysed. Out of them 92 (67.7%) strains were classified as those of human origin, 17 (12.5%) as those of bovine origin, and 27 (19.7%) were referred to as opportunistic. The study of cultural properties, virulence and drug sensibility demonstrated that the genitalia tuberculosis agent featured oligobacillary excretion, relationship between their rapid growth and the nature of material under observation, and multiple inoculation. Mainly low and medium virulence is determined. Overwhelming majority of the cultures show responses to the essential antituberculous drugs. PMID- 2110668 TI - [Investigation of pathogens in the foci of pulmonary and osteo-articular tuberculosis]. AB - The tubercle bacilli detection rate was determined by direct bacterioscopy and the culture plate method immediately in the disease foci in 123 patients with pulmonary tuberculosis and 78 patients with tuberculosis of bones and joints. The culture plate method was shown to have significant advantages over bacterioscopy. However, in some cases with negative responses to the culture plate test, bacterioscopy was the only procedure that detected the pathogen in resected lung tissues. Parallel use of 2 different media in the culture plate test provided higher frequency of the pathogen isolation. Cultures isolated from the lung foci were showed drug resistance in 1/4 of the cases. Cultures from the bone foci were in all the cases but one sensitive to all the drugs used. By their biological properties, all the isolates belonged to human tubercle bacilli. The necessity of microbiological investigation of pathogenes in tuberculosis foci is grounded. PMID- 2110669 TI - [Substantiation of the use of pepsidil in secretory insufficiency of the digestive glands caused by antitubercular drugs]. AB - The experiments on rats were undertaken to study the action of pepsidil to make up for the biosynthesis deficiency of digestive enzymes in the stomach and pancreas caused by antituberculous drugs (methazide + PAS, isoniazid + PAS, isoniazid + rifampicin + ethambutol). It was proved that pepsidil reduced an inhibiting action of antituberculous drugs on the activity of gastroenteric tract proteinases. The given condition should be taken into account when antituberculous treatment is conducted. PMID- 2110670 TI - [Effect of nitroglycerin preparations on indicators of central hemodynamics in patients with pulmonary tuberculosis complicated by chronic cor pulmonale]. AB - The effect of nitroglycerin drugs on central hemodynamic indices in 198 patients with pulmonary tuberculosis and chronic nonspecific pulmonary diseases was investigated. These studies revealed that in pulmonary tuberculosis, nitroglycerin caused blood pooling in peripheral vessels, a decrease in the central hemodynamic indices and an increase in the right heart. A single dose of nitrogen, 2.6 mg, given to a patient with hypokinetic circulation leads to the improvement of the central hemodynamic indices (circulating blood volume (CBV), stroke and cardiac indices, lung CBV) due to less peripheral angiospasm, peripheral circulation normalization and better blood supply to the right heart. A fortnight nitrogen regimen in a dosage of 2.6 mg thrice a day makes it possible to normalize the central hemodynamic indices and decrease pressure in the pulmonary artery in patients with pulmonary tuberculosis complicated by a chronic pulmonary heart with a hypokinetic circulation. PMID- 2110671 TI - [Meningeal tuberculosis in recent years]. PMID- 2110672 TI - Membrane feeding for infection of the reduviid bug Triatoma infestans with Blastocrithidia triatomae (Trypanosomatidae) and pathogenic effects of the flagellate. AB - To investigate the pathogenic effects of the trypanosome Blastocrithidia triatomae on Triatoma infestans, a method for direct infection by in vitro feeding was developed. After isolation of B. triatomae cysts from infected dead bugs, a suspension of cysts was disinfected with Desogen and Chloramin T, then mixed with sterile blood, spread on a sterile, parallel-grooved glass plate or a hammered aluminium plate and covered with a thin, sterile silicone membrane. The blood and plate were warmed to 36 degrees-38 degrees C by a heating plate. For investigation of the pathological effects, first instars of T. infestans were allowed to feed through the membrane on a mixture containing 10(6) cyst stages/cm3 blood. Development of about 30% of the third and fourth instar larvae was retarded as compared with that in uninfected control groups, and mortality rates increased in fourth and/or fifth instar larvae. Whereas total mortality rates of about 5% occurred in control groups, about 85% of the larvae died in the infected groups. These effects are very similar to those obtained in previous studies with coprophagic infections. PMID- 2110673 TI - Sarcocystis gigantea lectin--mitogen and polyclonal B-cell activator. AB - The present study further examined the in vitro response of human mononuclear cells (MNC) to the Sarcocystis gigantea lectin (SGL). The results confirm our previous report that SGL is mitogenic for human MNC. We now report that SGL is not only a potent mitogen but also a polyclonal activator for human peripheral B cells. As was true for pokeweed mitogen (PWM, 2 micrograms/ml), the addition of SGL (25 micrograms protein/ml) to cultures of MNC caused lymphocyte proliferation and B-cell maturation, indicated by a marked increase in IgG and IgM production. As measured by the [3H]-thymidine incorporation assay, SGL induced significantly higher proliferative responses than PWM (P less than 0.01, n = 24). The values obtained by SGL and PWM for IgG and IgM synthesis were essentially identical. As opposed to SGL, the sarcotoxin-containing fraction (SGTF) did not induce antibody formation or proliferative responses in human MNC. PMID- 2110674 TI - The effects of neutrophils and phospholipase A2 on transvascular albumin flux in isolated rabbit lungs. AB - In this study, addition of phospholipase A2 (PLA2) to salt-perfused isolated rabbit lungs containing rabbit polymorphonuclear leukocytes leads to an increase in pulmonary capillary permeability. We add 1.5 X 10(8) polymorphonuclear leukocytes to the perfusate. Next, indomethacin is added to the perfusate and 40 units of PLA2 are infused into the pulmonary arterial inflow of the lungs. At the end of the study, a lung sample is removed for measurement of transvascular albumin flux using I125-albumin as a measure of the permeability-surface area product. Control studies demonstrate no increase in transvascular albumin flux. Addition of a dual cyclooxygenase and lipoxygenase inhibitor, BW755C, to the perfusate prevents the increase in transvascular albumin flux. We conclude that PLA2 interacts with polymorphonuclear leukocytes to increase protein permeability. Since PLA2 can release endogenous arachidonic acid and platelet activating factor from cells, this suggests that release of such products may contribute to an increase in pulmonary capillary permeability from polymorphonuclear leukocytes. The ability of BW755C to prevent the increase suggests the possibility that lipoxygenase products contribute. PMID- 2110675 TI - Is the inhibitory effect of progesterone on endometrial prostaglandin F2 alpha production due to an inhibition of protein synthesis? AB - Progesterone and a high concentration of oestradiol (i) reduced the outputs of prostaglandin (PG) F2 alpha and, to a lesser extent, PGE2 from Day-7 and Day-15 guinea-pig endometrium in culture, but had little or no effect on the output of 6 keto-PGF1 alpha, (ii) prevented the increase in PGH synthase concentrations which normally occur in Day-7 and Day-15 guinea-pig endometrium during culture, and (iii) reduced the synthesis of secreted proteins by Day-15 guinea-pig endometrium in culture. These findings suggest that the inhibitory effect of progesterone and of high concentrations of oestradiol on endometrium PGF2 alpha synthesis is due to an inhibition of the syntheses of proteins involved in PGF2 alpha production. PMID- 2110676 TI - Modulation of prostanoid formation by various polyunsaturated fatty acids during platelet-endothelial cell interactions. AB - Previous studies have reported that polyunsaturated fatty acids (PUFAs) of nutritional interest may influence arachidonic acid (20:4n-6) metabolism in both platelets and endothelium, when tested separately. In the present study, platelets (PL) and cultured endothelial cells (EC) were first pre-enriched with eight different PUFAs for a two hour incubation in the presence of free fatty acid albumin pre-coated with each acid. EC, PL or both cell populations in combination, were then stimulated by thrombin (0.1 U/ml) for five minutes. Prostanoids were extracted, purified by thin-layer chromatography, and TxB2, 6 keto-PGF1 alpha and PGE2 were quantitated by radioimmunoassays. Prostanoids or dihomoprostanoids formed from cyclooxygenase substrates other than 20:4n-6 were measured by gas chromatography-negative chemical ionisation mass-spectrometry (GC MS). When co-incubated with EC, PL produced less TxB2 (-15 and -85% in the absence and presence of thrombin, respectively). In contrast, 6-keto-PGF1 alpha increased by 189 (basal conditions) and 358% (thrombin stimulation) when PL were added to EC, in agreement with PGH2 transfers from PL to EC. PGE2, produced by both cell populations, reached amounts which roughly represent the sum of those measured in PL and EC alone, except when cells were pre-enriched with linoleic (18:2n-6) and the n-3 family fatty acids (18:3-, 20:5- and 22:6n-3). 6-keto-PGF1 alpha was markedly inhibited by adrenic acid (22:4n-6), while this acid was converted into dihomo-6-keto-PGF1 alpha, the stable metabolite of dihomoprostacyclin. 22:4n-6 also inhibited TxB2 formation and was converted into dihomo-TxA2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110677 TI - Agranulocytosis, aplastic anemia, and leukemia: relevance to arachidonic acid metabolism. AB - Several agents including drugs, chemicals and viruses are known to induce agranulocytosis, aplastic anemia, and leukemia. The recent identification, characterization and cloning of several peptide regulatory factors, including granulocyte-macrophage-colony stimulating peptide regulatory factor (GM-CSF), erythropoietin, and interleukins and a study of their actions, suggest that agents producing agranulocytosis, aplastic anemia, and leukemia may interfere with the action of these factors. The agents that are capable of inducing these diseases and the various peptide regulatory factors have positive and/or negative actions on the prostaglandin system. Prostaglandins are known to be involved in the maturation and differentiation of the progenitor cells of the bone marrow and in erythropoietin-mediated erythropoiesis. Since prostaglandins influence immune response, modify genetic damage induced by drugs and chemicals, modulate gene action, and have feed-back control on the actions of peptic regulatory factors, it is likely that prostaglandins are involved in the pathogenesis of agranulocytosis, aplastic anemia, and leukemia. If so, this may lead to new therapeutic strategies in these hematological conditions. PMID- 2110678 TI - The effects of very low fat diets enriched with fish or kangaroo meat on cold induced vasoconstriction and platelet function. AB - Eighteen healthy volunteers consumed very low fat diets (less than 7% of daily energy) enriched with different sources of long chain (C20 and C22) polyunsaturated fatty acids (PUFA). Three diets provided 500 g/day of fish caught in the tropical waters of Australia (rich in arachidonic acid and docosahexaenoic acid), fish caught in the southern waters of Australia (rich in docosahexaenoic acid), or kangaroo meat (rich in linoleic and arachidonic acids). The fourth diet was vegetarian, similarly low in fat but containing no 20- and 22-carbon PUFA. An increase in the percentage of a particular C20 or C22 PUFA in the plasma phospholipid fraction in subjects consuming these low fat diets corresponded to the dietary PUFA composition. This study examined the effect of dietary modification of the level of arachidonic acid in plasma phospholipids on both traditional measures of platelet function and on cold-induced vasoconstriction. The cold pressor response, measured by venous occlusion plethysmography, was depressed in diets which elevated the levels of arachidonic acid in plasma lipids (kangaroo and tropical fish), enhanced after subjects consumed a diet which increased the levels of docosahexaenoic acid and eicosapentaenoic acid (southern fish diet), and was unchanged by the low fat vegetarian diet. There was no effect on bleeding time or platelet responsiveness. PMID- 2110679 TI - Light and electron microscope immunocytochemical localization of 5- and 12 lipoxygenases and cyclooxygenase enzymes in human granulosa cells from preovulatory follicles. AB - Cellular and subcellular distribution of 5- and 12-lipoxygenases and cyclooxygenase enzymes were investigated in human granulosa cells from preovulatory follicles using light and electron microscope immunocytochemistry. The results demonstrated that all three enzymes are present in granulosa cells but not in minor contaminating red blood cells. While the distribution of cyclooxygenase and 12-lipoxygenase was relatively uniform among the granulosa cells, 5-lipoxygenase was not uniformly distributed among these cells. All three enzymes are present in microvillus plasma membranes, rough endoplasmic reticulum, cytoplasm, nuclear membranes and chromatin. In summary, 5- and 12-lipoxygenases and cyclooxygenase enzymes, which catalyze the transformation of arachidonic acid into different eicosanoids, are present in several subcellular organelles including nuclei of granulosa cells from preovulatory follicles. PMID- 2110680 TI - Prostacyclin producing activity of human umbilical blood vessels in adrenergic innervated and non-innervated portions. AB - The present experiment was performed in order to clarify the significance of prostacyclin (PGI2) in the regulation of human umbilical blood flow. Distribution of adrenergic nerve fibers in umbilical cord was examined by means of a modification of the glyoxylic acid fluorescence histochemical technique. PGI2 producing activity in various portions of umbilical blood vessels was measured by platelet bioassay. Adrenergic nerve fibers were observed only in the region surrounding umbilical arteries at the fetal end of the cord. PGI2 producing activity of umbilical arteries was significantly lower in the innervated region than in the non-innervated region. There were no significant regional differences in umbilical vein which has no adrenergic innervation. The relationship between vascular PGI2 producing activity and adrenergic innervation, and the significance of PGI2 in the regulation of human umbilical blood flow are discussed. PMID- 2110681 TI - [Enlargement of the lymph nodes of the hilus hepatis: a further ultrasonographic sign of acute viral hepatitis]. AB - Enlarged hilar lymph nodes are usually reported as the most frequent US finding in acute viral hepatitis. The authors compared this finding with other pathologic conditions--i.e., asymptomatic cholelithiasis and acute cholecystitis--and with gallbladder wall thickening, which is also observed in acute hepatitis. From their results, they drew the following conclusions: a) lymph node enlargement at the hepatic hilum was a very frequent finding (11/15) at US in the patients with acute viral hepatitis; b) its occurrence was statistically more frequent than in both cholelithiasis and cholecystitis; c) gallbladder wall thickening was found in 53.3% of the patients with acute hepatitis; d) lymph node enlargement and gallbladder wall thickening were not related. The authors suppose enlarged lymph nodes to be suggestive of hepatic damage in a pattern of immunological hyperactivity rather than the result of inflammatory gallbladder conditions during acute hepatitis. Since only 2 cases could be followed, the authors cannot discuss the prognostic significance of enlarged lymph nodes after cytolytic enzymatic signs of viral hepatitis have disappeared. PMID- 2110682 TI - The effects of carotid body hypocapnia on ventilation in goats. AB - This study was designed to examine the influence of carotid body (CB) hypocapnia on ventilation by selectively perfusing the CB through an extracorporeal circuit in 19 goats. When PcbCO2 was decreased from normocapnic levels in 14 awake goats (delta PcbCO2 = 10.9 Torr), PaCO2 increased 5.6 Torr (P less than 0.05) and VE decreased 24% (P less than 0.001) (mean values). The ventilatory sensitivity to inspired CO2 was not changed by CB hypocapnia in 5 of these goats, but the response was shifted to the right. During CB hypocapnia, ventilatory instability, including apnea, was observed in 4 of 14 goats; this irregular breathing continued at elevated levels of PaCO2. In 5 anesthetized goats, CB hypocapnia (delta PcbCO2 = 18.0 Torr) decreased VE by 70% in the intact state, but produced no significant ventilatory depression after CB denervation. We conclude that CB hypocapnia depresses ventilation in both awake and anesthetized goats mostly through CB chemoreceptor effects, and suggest that this hypoventilation may predispose to ventilatory instability in some animals. PMID- 2110683 TI - Fecal excretion of radiolabeled (51CrCl3) proteins in patients with Crohn's disease. AB - Intestinal leakage of plasma proteins was studied in 69 patients with Crohn's disease. In vivo labeling of plasma proteins was performed by intravenous injection of trace amounts of 51CrCl3. Complete fecal collection was done for 5 days, carefully avoiding contamination with urine. The daily fecal radioactivity was measured in a whole-body counter and expressed as a percentage of given dose. In patients with a classic localization of the disease the mean fecal excretion of radiolabeled proteins was 2.8% (range, 0.8-5.5%). The excretion was significantly higher in patients with extensive ileojejunal involvement (8.8%; 4.3-14.0%) and in patients with a total colitis (5.5%; 2.0-8.2%) but not different from that in patients with prestomal recurrent ileal disease (3.5%; 1.6 5.3%). A close correlation was found between fecal excretion of 51Cr and extent of the small-intestinal disease as measured at laparotomy (r = 0.86, p less than 0.001). A highly significant inverse relationship was also demonstrated between fecal protein excretion and serum albumin concentration in patients without septic complications of the disease (r = -0.57, p less than 0.001). A pre existing septic complication made the patients hypoalbuminemic despite limited intestinal loss of protein. It is concluded that estimation of intestinal protein loss is a sensitive and simple test for assessment of the extent of the small intestinal involvement in patients with Crohn's disease. The test may be of value in patients with unclear radiologic findings and in patients with hypoalbuminemia of unknown cause. PMID- 2110684 TI - Phospholipase C from Clostridium perfringens stimulates phospholipase A2-mediated arachidonic acid release in cultured intestinal epithelial cells (INT 407). AB - The mechanisms by which phospholipase C from Clostridium perfringens stimulates release of arachidonic acid (AA) in cultured intestinal epithelial cells (INT 407) were investigated. INT-407 cells were first allowed to incorporate 14C labeled AA into their phospholipids; the labeled cells were then exposed to phospholipase C, and the release of free 14C-AA was determined. Phospholipase C caused a rapid (3 min) intracellular rise of free 14C-AA, followed by a considerable, dose- and time-dependent release of 14C-AA into the extracellular medium. For comparison, the calcium ionophore A23187 also caused a rapid mobilization of free 14C-AA, but a much lower extracellular 14C-AA release than phospholipase C during longer (1 h) incubation. The 14C-AA release was accompanied by a degradation of 14C-myo-inositol-labeled phosphatidylinositols and was reduced by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2 methylpiperazine (H-7). Both phospholipase C- and A23187-stimulated 14C-AA release was associated with degradation of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol and was reduced by nordihydroguaiaretic acid and 4-bromophenacyl bromide, two known phospholipase A2 inhibitors. In addition, the 14C-AA release was reduced by the calmodulin inhibitors trifluoperazine, compound 48/80, and N-(6-aminohexyl)-5-chloro-1 naphthalene-sulfonamide (W-7). These findings indicate that phospholipase C from C. perfringens stimulates phospholipase A2-mediated AA release from human intestinal epithelial cells and suggest that this stimulation is brought about via processes involving phosphatidylinositol breakdown and activation of calmodulin and protein kinase C. It is possible that this phospholipase C-evoked AA release may contribute to the mucosal pathologic condition in diseases with altered intestinal microbial flora. PMID- 2110685 TI - Experimental models of hepatic fibrosis: a review. AB - No experimental model reproduces exactly human liver fibrosis by etiology. Nonetheless, each of the models reviewed in this article has served to enhance our understanding of pathogenetic mechanisms of liver fibrosis. There have been important common findings derived from several different models. The best example is the role of Ito cells in liver fibrogenesis. Involvement of Ito cells was consistently seen in the experimental models regardless of whether the fibrogenic stimulus was nutritional, hepatotoxic, or immunologic. Cellular and molecular mechanisms of Ito cell activation have begun to be explored in different models. Another example is the role of TGF beta in liver fibrogenesis. In both murine schistosomiasis model and Tsukamoto-French rat model, TGF beta was shown to be closely associated with fibrogenesis. With both in vitro and in vivo experimental approaches using cellular and molecular techniques, the experimental model of liver fibrosis will continue to provide data on the pathogenetic mechanisms of liver fibrogenesis. Future genetic and molecular approaches may allow development animal models with liver fibrosis that is inducible and genetically similarity to that of man. PMID- 2110686 TI - [The key problems of clinical hepatology]. PMID- 2110687 TI - Medical community should focus on technology assessment. PMID- 2110688 TI - [The use of bacteriological analysis of the blood in the diagnosis of death by drowning]. AB - Investigation of blood samples from the femoral vein of subjects drowned in water and died of other causes (control) was carried out. Penetration of microflora contained in water into the bloodflow of the drowned people was shown. Possibility of using bacteriologic analysis of the postmortal blood to diagnose death from drowning was stated. Ps. putida and Ps. fluorescens. that were not present in the blood of persons who had died of causes other than drowning were recommended as test bacteria. Selective media and methods to isolate the bacteria from the cadaveric blood were chosen. PMID- 2110689 TI - The connection between macro and micro levels: states' spending for hospitals and their suicide rates. AB - A trend analysis of states' spending for hospitals and their suicide rates in 1960, 1970, 1980, and 1984 showed that states' spending for hospitals was not directly related to their suicide rates until 1984. The analysis also showed that in 1984, states' spending for hospitals was not only directly and inversely related to their suicide rates, but also accounted for a 5% increase in their variance. Drawing on Durkheim's theory of social integration, the analysis took into account the effects of states' divorce rates, rates of population change, population density, and the economic level and racial composition of states' population. Following policy trends in health care more generally, the findings call attention to the wider implications of institutional norms of cost containment at all costs and states' suicide rates, and thus to the largely ignored connection between macro and micro levels. PMID- 2110690 TI - Genetic approaches to ciliate pattern formation: from self-assembly to morphogenesis. AB - In the cortex of ciliates, thousands of basal bodies, with their associated cytoskeletal appendages and networks, are arranged in an elaborate pattern whose reproduction at division involves complex morphogenetic movements. Genetic analysis demonstrates that pattern formation relies both on local constraints imposed by the pre-existing organization, and on the differential interpretation of inductive signals by different cell territories whose individual developmental properties are reset at each division. PMID- 2110691 TI - [The effect of thiamine and its metabolites on pepsin and trypsin activity]. AB - The presence of thiochrome in the incubation medium increases the pepsin activity. Thiamine pyrophosphate decrease the pepsin and trypsin activity. The established facts may be important for the physiological regulation of proteases activity in the stomach-intestine tract. PMID- 2110692 TI - [Changes in kinetic properties of pyridoxal-dependent enzymes during dietary vitamin B6 deficiency in rats]. AB - The erythrocyte aspartate aminotransferase and renal and intestinal glycogen phosphorylase activities in rats are determined as dependent on their provision with vitamin B6. It has been shown that the aspartate aminotransferase activity decreases and the shape of the aspartate concentration-activity curve changes in the vitamin B6-deficient animals. The B6 insufficiency does not affect the intestinal mucosa glycogen phosphorylase. However the renal phosphorylase activity decreases by 30 percent in the vitamin B6 deficient rats. It occurs due to changes in the affinity of phosphorylase A and B to glucose-1-phosphate but not to AMP. The activation of these investigated enzymes by exogenous pyridoxal phosphate reveals no essential differences between the vitamin B6-deficient and normal rats. The possible causes of the observed changes in the aspartate aminotransferase and phosphorylase activity are discussed. PMID- 2110693 TI - [Insurance and gene analysis]. PMID- 2110694 TI - Effect of size and temperature on the quantity of immunoglobulin in channel catfish, Ictalurus punctatus. AB - Concentrations of serum immunoglobulin (Ig) were determined for 30 channel catfish from pond water at 10 degrees C. These values were compared to measurements of 15 channel catfish from pond water at 30 degrees C. Channel catfish from 10 degrees C pond water had no significant (P greater than 0.05) different Ig concentrations (mean, 398 mg/dl) than catfish from 30 degrees C pond water (mean, 367 mg/dl). Serum Ig concentrations appear not to be different in cold (10 degrees C) vs warm (30 degrees C) pond water for 37.5-45 cm catfish. Channel catfish, 7.5-15 cm (n = 24) had significantly (P less than 0.05) lower Ig levels (mean, 104 mg/dl) than catfish either 7.5-25.5 cm (n = 57, mean, 232 mg/dl) or 37.5-45 cm (n = 45, mean, 388 mg/dl). Also, catfish 17.5-25.5 cm had a significantly (P less than 0.05) less Ig than catfish 37.5-45 cm. The concentrations of serum Ig increase with size (P = 0.0001) of catfish. The mean Ig concentration for 7.5-45 cm catfish (n = 126) was 263 mg/dl. The Ig concentration range was 44 to 650 mg/dl of serum. PMID- 2110695 TI - Morphometric comparison of mitochondria and myofibrils of cardiomyocytes between hypertrophic and dilated cardiomyopathies. AB - We performed an ultrastructural, morphometric comparison of mitochondria and myofibrils of cardiomyocytes using endomyocardial biopsy specimens in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Biopsies came from the right ventricular side of the interventricular septum in nine patients with HCM, nine with DCM, and nine controls with arrhythmia and/or ST depression. Morphometric analysis was carried out using electron microscopic photographs and an image analyser. Mitochondria were significantly greater in number and smaller in size in HCM than in the control group. In DCM, the size of mitochondria was also significantly smaller than in the control group, although their number was similar to that of the control group. No statistically significant difference was found regarding the size of mitochondria between HCM and DCM. The percentages of both mitochondrial and myofibrillar areas in cytoplasm were smaller in the DCM than the HCM and control groups, though no difference was seen between the latter two. The ratio of mitochondrial area to myofibrillar area was almost the same in each group. These results suggest increased mitochondrial function to match hypertrophic cardiomyocytes in HCM, and decreased mitochondrial function and cardiomyocytic contractility in DCM. PMID- 2110696 TI - Transferrin receptor expression in tumours of the human nervous system: relation to tumour type, grading and tumour growth fraction. AB - The expression of transferrin receptor (Tr) was investigated by means of immunohistochemistry in 101 tumours of the human central and peripheral nervous system. The results were compared with the proliferative activity of the tumours, determined by immunostaining for the proliferation-associated antigen Ki-67. In addition to immunostaining of normal and proliferated blood vessel endothelium and of a fraction of tumour infiltrating lymphocytes, we observed staining for Tr in a variable fraction of neoplastic cells of all histological tumour types. Immunoreactivity in the majority of tumour cells was found only in anaplastic tumours such as glioblastomas. Furthermore, a positive correlation between Tr expression and the Ki-67 growth fraction was established for gliomas. Non-glial tumours strongly expressing Tr included one metastatic rhabdomyosarcoma, one intracerebral malignant lymphoma, two of four plasmocytomas and seven of nine metastatic carcinomas. Our results indicate that immunohistochemistry for Tr and Ki-67 can provide additional information about the biological behaviour of nervous system tumours, thus complementing conventional histopathological criteria for anaplasia. PMID- 2110697 TI - Histological and ultrastructural effects of cyclosporin A on normal human skin xenografted on to nude mice. AB - Cyclosporin A (CsA) is a potent immunosuppressant with a selective activity on T helper lymphocytes. However, CsA also exerts biological effects on non-lymphoid cells (fibroblasts, endothelial and epithelial cells). CsA can inhibit in vivo and in vitro DNA synthesis of epidermal keratinocytes (EK) and induces in vivo morphological alterations of kidney epithelial cells. In the present study we investigated the in vivo effects of a short-term CsA treatment (50 mg/kg per day) on DNA synthesis (evaluated through 5-bromo-2'-deoxyuridine incorporation) and on the histological features of normal human skin xenografted (NHSX) on to congenitally athymic nude mice. When compared with control NHSX, CsA induced a statistically significant inhibition of DNA synthesis of NHSX EK. At the light- and electron-microscopic level, apart from a decrease in the thickness of the viable epidermis of NHSX (statistically non-significant), no noticeable differences between treated and control NHSX could be detected. EK, Langerhans cells and melanocytes appeared morphologically unaffected by CsA and no signs of acute toxicity (giant mitochondria, vacuolization, microcalcifications) were seen. These results suggest that CsA exerts a subtle effect on human EK; indeed, despite an unequivocal antiproliferative activity, no significant histological changes related to the acute CsA toxicity seem to be induced on the various epidermal cell types. PMID- 2110698 TI - Complementary expression of melanosomal antigens and constant expression of pigment-independent antigen during the evolution of melanocytic tumours. AB - We have generated monoclonal antibodies (MoAbs) against melanosomal proteins (MoAb 1C11 and MoAb HMSA-1) and a cytoplasmic protein strongly synthesized in neoplastic melanocytes but not associated with melanogenesis (MoAb 7H11). An immunohistochemical study of paraffin sections showed that nearly 90% of epidermal neoplastic melanocytes, including melanomas, expressed 1C11 antigen, whereas this antigen was poorly preserved in dermal melanocytic cells except melanomas. HMSA-1 antigen was expressed in a complementary manner to 1C11 antigen, being found in dermal naevus cells but not generally in the epidermal regions, except for dysplastic naevi and melanomas. In contrast, 7H11 antigen was distributed in nearly 90% of melanocytic tumours except solar lentigo and lentigo maligna lesions. The failure of MoAb 1C11 to react with dermal melanocytes may reflect a subtle alteration in melanogenesis during tumour evolution. Overall, the combined use of MoAbs serves as an accurate diagnosis of melanocytic tumours, the pigment-independent MoAb 7H11 being particularly useful for amelanotic and metastatic lesions. PMID- 2110699 TI - The reproducibility of cytomorphometrical grading of bladder tumours. AB - The reproducibility of cytomorphometrical nuclear area measurements on transitional cell carcinoma is studied. The inter-individual consistency is low (r = 0.55, P = 0.0005) when nuclei for measurement are chosen at random. When we use a systematic analysis based on cell situation and cytological features of malignancy to select the 50 nuclei for measurement per slide, the consistency between two technicians appears to be significantly higher (r = 0.90, P = 0.015). Not only interindividual consistency increases using the selection, but the correlation with histological tumour grade also improves significantly for both technicians. The results show that cytomorphometry is a method of grading bladder carcinoma when an accurate selection of nuclei to measure is used. Cytomorphometrical studies should contain a clear description of the way the nuclei for measurement are chosen. PMID- 2110700 TI - The immunopathology of Schistosoma mansoni granulomas in human colonic schistosomiasis. AB - The immunopathology of Schistosoma mansoni infection was studied in colonic biopsies obtained from 14 patients with established schistosomiasis. The characteristic lesions of this parasitic infection are mainly induced by the presence of living eggs in the tissue. Different types of lesions can be present simultaneously. The earliest lesions contain T-lymphocytes as well as accessory cells around living eggs. They transform into granulomas composed of eosinophils, T-lymphocytes, a few B-lymphocytes and large mononuclear cells expressing major histocompatibility (MHC) class II antigens. These cells are also Mac 387 positive. This means that they are monocytes/macrophages freshly recruited from the blood. In other, probably older, granulomas, MHC class II positive cells tend to disappear and the centrally located multinucleated giant cells are negative for antibodies directed against MHC class II antigens. It appears thus that the composition of the granulomas in schistosomiasis is variable. The lesions may have characteristics of cell-mediated immunity and/or of a foreign-body reaction. Contrary to what is often seen in Crohn's disease or intestinal tuberculosis no major hyperplasia of the lymphoid tissue is observed in the colon in association with S. mansoni infection. PMID- 2110701 TI - Solid-cystic tumour of the pancreas. An endocrine neoplasm? AB - Immunohistochemical studies and DNA flow-cytometric investigations were performed in a case of solid-cystic tumour of the pancreas in a 35-year-old woman. All tumour cells were immunoreactive for the neuroendocrine cell markers chromogranin A and neuron-specific gamma-enolase. Moreover, about 10% of tumour cells were immunoreactive for insulin, while hypoglycaemia was absent. Few tumour cells (less than 1%) were immunoreactive for somatostatin, and no cells were found to be immunoreactive for pancreatic polypeptide or glucagon. No immunoreactivity was present for duct cell marker carcino-embryonic antigen and only individual cells were reactive for alpha 1-antitrypsin. Nuclear DNA content of the tumour cells was diploid and the proliferative activity was low. In confirmation of some reports on neuroendocrine markers in solid-cystic tumour of the pancreas, our findings support the theory that the lesion is a hormonally inactive neuroendocrine pancreatic tumour. PMID- 2110702 TI - The mechanism of aphidicolin bioinactivation by rat liver in vitro systems. AB - 1. Aphidicolin is shown to undergo rapid metabolism by rat-liver microsomes resulting in its inactivation and loss of its DNA polymerase alpha/delta inhibition. Metabolism of aphidicolin was not observed with cytosolic enzymes of rat liver and was inconsistent with the involvement of microsomal 3 alpha hydroxysteroid oxidoreductases. 2. Rates of aphidicolin inactivation as a function of microsomal enzyme induction (per nmol cytochrome P-450) followed the order: untreated microsomes greater than dexamethasone-induced greater than phenobarbital-induced greater than beta-naphthoflavone-induced greater than clofibrate-induced. 3. The principal metabolic process, constituting greater than 90% of the metabolic profile, produces 3-ketoaphidicolin 2, which exhibits approximately 10% of the activity of aphidicolin in inhibition of DNA polymerase alpha. This metabolic transformation, the oxidation of an alcohol to a ketone, is an unusual, but not unique conversion, for cytochrome P-450. 4. 3-Ketoaphidicolin 2 is an intermediate and ultimately undergoes 18-dehydroxymethylation to produce 18-noraphidicolinones 3, which are inactive in the inhibition of DNA polymerase alpha. 5. A specific constitutive cytochrome P-450 isozyme, involved in endogenous steroid regulation, was implicated as the species responsible for aphidicolin metabolism in vitro. PMID- 2110703 TI - Reactogenicity and immunogenicity of combined vaccines for bacteraemic diseases caused by Haemophilus influenzae type b, meningococci and pneumococci in 24-month old children. AB - To find a wide spectrum vaccine against bacteraemic disease in childhood, we immunized 293 Finnish children at 24 months of age intramuscularly with different combinations of the currently available vaccines, namely Haemophilus influenzae type b polysaccharide-protein conjugate vaccine (PRP-D) mixed with meningococcal and/or pneumococcal capsular polysaccharide vaccines. All the vaccines were immunogenic. The increase in antibody concentration after vaccinations was not affected by the number of polysaccharide antigens. Although no serious reactions were seen, the frequency of both local and fever reactions was greater in groups that received several vaccine antigens. Halving of the vaccine dose decreased the reactogenicity without impairing the immunogenicity. PMID- 2110704 TI - Protective effect of heterologous gram-positive vaccine against lethal upper respiratory tract infection with type M50 group A streptococci in mice. AB - Type M50 group A streptococci are exceptional for their virulence in mice. However, intranasal (i.n.) vaccination with heat-killed group A streptococci, either of type M50 or M55, or an M12 strain deficient in M-protein, protected mice against i.n. challenge with M50 streptococci (82, 88 and 83% survival, respectively). Significant resistance against M50 streptococci was also noted by i.n. application of heat-killed Lactobacillus fermenti (81% survival) as well as two strains of pneumococci (50 and 79% survival). In contrast, no protective effect was obtained using heat-killed trypsin-treated M55 streptococci. Nor did vaccination with Escherichia coli and Pseudomonas aeruginosa induce protection against type M50. Thus, M protein was not required for immunity against type M50. The results call for a revision of the hitherto accepted view that M proteins are the only candidates for mucosal vaccines against group A streptococci. PMID- 2110705 TI - [Significance of serum prolactin determination in the differential diagnosis of psychogenic seizures--exemplified by 2 case reports]. AB - Conversion neurotic bodily disorders manifest themselves mainly in the motor system (e.g. psychogenic paralyses and gait disturbances). Psychogenic seizures are observed as well; these may also become manifest as hystero-epilepsy association with an organic convulsive disease. The described symptoms "stimulate" a bodily process, so that the differential diagnosis frequently poses problems. A rapid and clear diagnosis is of decisive importance for a well aimed therapy. The determination of an increased prolactin content in serum in the postictal phase, expressing an epileptological event, constitutes an important element in separating a psychogenic from an organic seizure. The differential diagnosis of cerebral and psychogenic seizures should, in addition to identifying a possible psychopathological process, utilize this diagnostic tool. This will be demonstrated by presenting two cases of female adolescents with epileptic an psychogenic seizures. PMID- 2110706 TI - [Perioperative blood transfusions. Changed indications and new alternatives]. AB - The surgeon has to keep abreast of changing advantages and disadvantages as well as alternatives in the context of homologous blood transfusions. We ought to realise that normovolaemic anaemia is better tolerated than we used to assume in the past. It is no longer necessary to provide transfusions to patients with 10 g/% Hb. About 8 g/% should rather be considered the adequate threshold. Possible transmission of hepatitis and AIDS virus is a genuine risk associated with blood transfusion. No hard evidence has yet been produced to immunosuppression and effects on the prognosis of cancer patients. More attention will have to be given in the future to preoperative supply of blood for autohaemotherapy. PMID- 2110707 TI - [The GnRH-TRH double stimulation test before and following surgical removal of uterine leiomyoma]. AB - In seven patients with uterine leiomyomatosis investigated the function of hypothalamic-pituitary-ovarian axis has been with a GnRH-TRH-double stimulation test. The basal levels of estradiol, progesterone, LH, FSH and PRL as well as the pituitary reaction after the stimulation were determined. Three patients had a tendency to a basal hypergonadotropinemia and four patients to hypoprolactinemia. The pituitary reaction following the stimulation does not show any connection between leiomyoma and secretion pattern of the hypothalamic-pituitary-ovarian axis. PMID- 2110708 TI - [Comparison of the effects of carbonated baths with those of carbon dioxide baths, "dry baths"]. AB - Therapeutic activities of CO2 water bathes are explained by a synergism between many factors. The first ones are related to immersion it-self: hydrostatic pressure and Archimedes force inducing orthosympathetic inhibition and muscular relaxation. The second ones depend on the pharmacological properties of carbon dioxide acting directly on the blood vessels of the skin, causing vasodilation and heat sensation. As "dry" carbon dioxide bath is devoid of the physical factors which are necessary for a successful therapeutic activity, such an administration has no interest in balneotherapy. PMID- 2110709 TI - [Use of Nutramin VLI Spofa for parenteral nutrition in the early post-injury period in polytrauma]. AB - The solution of branched-chain amino acids of gradually increasing concertration ranging from 22.7 to 43 per cent was administered to 15 patients with polytrauma as part of parenteral nutrition. Parenteral nutrition was started with during 24 hours after the trauma. The effect of parenteral nutrition was objectified by a twenty-four hour balance of water, ions, energy and nitrogen and by a follow-up of kinetics of amino acids in the plasma. It was found out that the increase of the share of branched-chain amino acids up to 43 per cent resulted in a pharmacodynamically efficient level of valine. There occurred gradual adjustment both of the levels of other aminoacids in the plasma and other metabolic changes including the restoration of proteosynthesis. PMID- 2110710 TI - Feline E. coli bacteremia--effects of misoprostol/scavengers or methylprednisolone on hemodynamic reactions and gastrointestinal mucosal injury. AB - Live E. coli were infused i.v. in cats to induce gastrointestinal mucosal injury and the gastric mucosa was exposed to bile and a luminal pH of 1. A gastric lesion index was calculated and intestinal injury was graded. The effects of i.v. methylprednisolone before and after induction of bacteremia were compared with those of intragastric misoprostol combined with i.v. superoxide dismutase (SOD) and catalase and with a control group. Methylprednisolone, but not misoprostol/SOD/catalase, significantly reduced the gastric lesion index (p less than 0.05). The duodenum/small intestine was significantly injured in 4/6, 2/6 and 4/6 cats in the misoprostol/SOD/catalase, methylprednisolone and control groups, respectively (NS). End gastric luminal pH was 3.9, 2.7 and 4.5 in the respective groups (p less than 0.05), with systemic arterial pH 7.15, 7.15 and 7.32 (NS). Mean arterial pressure and cardiac output were improved with methylprednisolone. Misoprostol/SOD/catalase reduced late hypotension. Pulmonary arterial pressure rose to c. 200% of basal in all groups. Methylprednisolone, but not misoprostol/SOD/catalase, thus protected the gastric mucosa from sepsis induced gastric injury concomitant with reduced disappearance of protons from the gastric lumen, but did not significantly affect small-bowel damage. Hemodynamic responses were significantly improved in methylprednisolone-pretreated cats. PMID- 2110711 TI - Comparative study of the therapeutic effects of glibenclamide or the fixed combination of glibenclamide-phenformin with those of gliclazide or chlorpropamide. AB - This study was designed to compare the therapeutic effects of glibenclamide or the fixed combination of glibenclamide-phenformin with those of gliclazide, chlorpropamide or biguanides in non-insulin-dependent diabetes. It is divided into two parts: a) in the retrospective study (473 subjects), glucose control of patients who were transferred from chlorpropamide, gliclazide, glibenclamide, glibenclamide + biguanide or metformin to the fixed combination glibenclamide phenformin in the same tablet (2.5 mg and 25 mg, respectively) was monitored. A statistically significant decrease of blood glucose and glycosylated hemoglobin values was found under the combination of glibenclamide-phenformin contained in the same tablet in contrast to the values obtained with the treatment with glibenclamide, gliclazide, chlorpropamide, combination of glibenclamide and biguanides, metformin, and insulin. b) In the prospective study (57 subjects), the patients were transferred from chlorpropamide or gliclazide to glibenclamide for 3 months and then reallocated to the previous treatment for 3 additional months. It was found that under glibenclamide, glucose control was significantly better than under chlorpropamide or gliclazide. In conclusion, glibenclamide, a second generation sulfonylurea, and the fixed combination glibenclamide phenformin in the same tablet are more effective compared to the other antidiabetic agents here studied and lead to a better control of type II diabetic patients. There was no increase in plasma lactic acid concentration in all patients studied before and after having received the fixed combination of glibenclamide-phenformin in the single tablet form. PMID- 2110712 TI - LH pulsatility and response to a single s.c. injection of buserelin in polycystic ovary syndrome. AB - The present study was undertaken in order to determine whether patients with polycystic ovary syndrome (PCOS) have LH pulse frequency and/or amplitude higher than those in normal cycling women during the follicular phase, and, if so, to establish possible factors which might influence LH secretion in PCOS. The study was conducted on 14 PCO patients (aged 19-30 years), who were subdivided according to the data on their cycle abnormality into 2 groups: amenorrheic (Am PCOS, n = 9) and oligomenorrheic (O-PCOS, n = 5). LH pulsatility was assessed in the early follicular phase in controls (n = 5) and O-PCOS and at any time in Am PCOS. Blood samples were taken every 10 minutes for 4 hours. Pulse analyses of LH data were performed using the Munro program. The buserelin test was performed on the same day by injection of 40 micrograms of buserelin (blood samples were taken every 60 minutes for the following 10 hours). Eleven PCO patients and 12 control subjects had an oral glucose tolerance test (oGTT) (blood samples were taken every 60 minutes for glucose, insulin and C-peptide measurements). Both mean LH pulse frequency and mean pulse intervals were not distinguishably different in PCO women (Am and O) and controls. In contrast, the mean pulse amplitude was significantly higher in the Am-PCOS group than in O-PCOS women and controls (p less than 0.02 and p less than 0.001, respectively). A significant positive correlation was established between nadir LH concentrations and LH pulse amplitude (r = +0.966, p less than 0.001). The LH response to buserelin stimulation was significantly higher in Am-PCOS than in O-PCOS (p less than 0.004). A highly significant positive correlation was observed between LH pulse amplitude and insulin response during oGTT (p less than 0.001) in PCO subjects. Basal (prebuserelin) LH concentrations correlated significantly with fasting insulin levels (p less than 0.008) and insulin and C-peptide responses to oGTT. These results allow us to conclude the following: 1. An increased LH pulse amplitude and an exaggerated LH response to buserelin observed in amenorrheic PCO subjects compared to those in oligomenorrheic PCO subjects fail to support the hypothesis of an intrinsic hypothalamo-pituitary abnormality. 2. The relationship between fasting and glucose-stimulated insulin levels with LH nadir concentrations, pulse amplitude and response to buserelin suggests an etiological role of insulin in the pathogenesis of PCOS. PMID- 2110713 TI - Endocrine profile associated with estrogen and progesterone receptors in leiomyoma and normal myometrium. AB - In leiomyoma and normal myometrium estrogen receptors act independently at low or high levels of the normal serum steroid range in the menstrual cycle. It might be an inherent characteristic of leiomyomas, which results in their progressive growth in the absence of any abnormal stimulation. In the secretory phase of the menstrual cycle, serum progesterone suppresses estrogen receptor concentrations in leiomyoma. In the present study serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) showed direct as well as inverse correlations with estrogen and progesterone receptors in different phases of the menstrual cycle. PMID- 2110714 TI - Fusion of LuxA and LuxB and its expression in E. coli, S. cerevisiae and D. melanogaster. AB - Luciferase from Vibrio harveyi is encoded by two adjacent genes, luxA and luxB. The two genes were fused by replacing a segment extending from near the end of luxA into the N-terminal end of luxB by a synthetic oligonucleotide. The construction removed the TAA stop codon at the end of luxA, the intervening region of 26 base pairs, and the initial methionine of luxB. A Smal site was included at the junction between the two genes and an AatII site was created near the end of luxA without altering its amino acid sequence. In Escherichia coli the fused luxAB gene could be expressed to produce functional luciferase that gave about 20% of the activity in cells without the fusion. An out-of-frame ATG exists close to and preceding the ATG of the luxA gene. This was removed and the entire fused gene bracketed by several restriction enzyme sites. The fused luxAB gene was successfully expressed in Saccharomyces cerevisiae and Drosophila melanogaster by transferring it to appropriate plasmid vectors. PMID- 2110715 TI - Immunopathology of cerebrospinal fluid in the HIV infection. PMID- 2110716 TI - Clinical value of HIV p24 Ag in cerebrospinal fluid of symptomatic or asymptomatic HIV-infected patients. PMID- 2110717 TI - HIV-1 isolation and p24-antigen detection in cerebrospinal fluid of subjects with neurological abnormalities related to AIDS. PMID- 2110718 TI - Immunological study in newborns at risk for HIV-1 infection. AB - We have performed an isoelectric focusing study (IEF) to detect the presence of oligoclonal bands (OB) in serum and in 5 of the correspondent cerebrospinal fluid (CSF) from 14 HIV-seropositive mothers and their newborns. CB were also searched in serum from 4 newborns every 3 months over a period of 12 months. OB were present in 8/14 sera and in 3/3 CSF obtained from the mothers; CSF OB were different from the correspondent serum indicating an intrathecal synthesis. OB were also visualized in serum, but not in CSF, from 3 newborns studied at birth: two of them died respectively at 4 and 5 months of age. One of the 4 newborns that were serially studied showed the appearance of OB at 12 months of age. A comparative study between sera obtained at the moment of delivery from the mother and her newborn showed that oligoclonal banding patterns were superimposable. Our data indicated that: 1) the IgG forming OB in the newborn's serum derive from a passive filtration from mother's serum; 2) the presence of OB seems to be an unfavourable prognostic feature in infants at risk for HIV-1 infection. PMID- 2110719 TI - Anthropometric measurements as predictors of mortality in a community population aged 70 years and over. AB - Corrected arm muscle area (CAMA), triceps skin-fold thickness (TSF) and body mass index (BMI) were measured in a community sample of 758 people who were then followed for 40-46 months. Percentile values were calculated for each sex in 5 year age groups. The relative risk of death of those in the upper and lower percentiles was compared with those between the 10th and 90th percentiles, controlling for age and sex. Subjects below the 5th percentile for CAMA, TSF and BMI and between the 5th and 10th percentile for CAMA had a significantly increased risk of death. There was no increased risk of death in those subjects above the 90th percentile in any measurement. In the logistic regression model, both low CAMA and low TSF were associated with a significantly increased risk of subsequent mortality. Poor nutritional state shown by low muscle bulk and fat stores was an important predictor of mortality, but obesity had no adverse effect on survival. PMID- 2110720 TI - Medical decision making: practical points for practicing radiologists. PMID- 2110721 TI - Radiologic investigation of dysphagia. PMID- 2110722 TI - Pitfalls in the radiologic diagnosis of lung cancer. PMID- 2110723 TI - Pulmonary blastomycosis: findings on chest radiographs in 63 patients. AB - Posteroanterior and lateral chest radiographs of 63 patients with proved pulmonary blastomycosis were evaluated to determine the most common findings. Included in the analysis were the location of the pulmonary infiltrates, the distribution and parenchymal patterns of disease, and the prevalence of adenopathy, pleural effusions, and/or cavity formation. Blastomycosis pneumonitis involved more than one pulmonary lobe in 21 patients and a single upper lobe in 27 of 63 patients. Forty-eight of the 63 patients had air-space consolidation. In nine of the 63 patients, a pulmonary mass was the major abnormality seen on radiographs. Approximately one fifth of the patients had associated pleural effusions and/or mediastinal or hilar adenopathy. Twenty-three patients (37%) had cavitation within the area of pulmonary consolidation. These findings suggest that blastomycosis should be considered when chest radiographs show air-space infiltrate in the upper lobes or in more than one lobe of the lung, especially when the infiltrate is associated with pleural effusions, cavitation, lymphadenopathy, and/or a paramediastinal mass. PMID- 2110724 TI - Percutaneous biopsy of thoracic lesions: value of sonography for needle guidance. AB - Fluoroscopy and CT are widely used to guide percutaneous needle biopsy of thoracic lesions. However, some lesions are not sufficiently visible on fluoroscopy and others are dangerous to access on CT without real-time monitoring. When these are the circumstances, sonographic guidance may be helpful. Real-time sonography was used to guide percutaneous needle biopsy in 124 patients with thoracic lesions. The indications for sonographic guidance included pulmonary, pleural, or mediastinal lesions in contact with the chest wall, including lesions near the heart or great vessels (n = 12); lesions in the apical region (n = 5); lesions in a juxtadiaphragmatic location (n = 6); small lung nodules adjacent to the chest wall (n = 16); and peripheral tumors with adjacent pleural effusion (n = 4). A diagnosis was made in 74 (90%) of 82 malignant lesions and in 24 (67%) of 36 benign lesions. Complications included pneumothorax (n = 5), hemoptysis (n = 1), and hemothorax (n = 1). The advantages of sonographic guidance are that the sonographic equipment is mobile and real-time monitoring makes the procedure safer. Its limitations are that it cannot be used when aerated lung or free air (pneumothorax) lies between the chest wall and the lesion and that cavitary lesions are difficult to sample by biopsy. Our results show that the use of sonographic guidance considerably expands the number of thoracic lesions amenable to percutaneous biopsy. PMID- 2110725 TI - Bilateral internal mammary artery aneurysms: a previously unreported cause for an anterior mediastinal mass. PMID- 2110726 TI - Stereotactic fine-needle aspiration for cytologic diagnosis of nonpalpable breast lesions. AB - Fine-needle aspiration for cytologic diagnosis was performed on 219 nonpalpable breast lesions by using a stereotactic localization technique. Cytologic results were correlated with mammographic findings, and therapeutic decisions were based on the results of both procedures. Representative cytologic material was obtained in 74% of the lesions. Strict criteria of representativeness were observed. If only cases with representative cytologic yield are considered, the sensitivity was 93% and the specificity was 97%. The predictive values were high except for the predictive value of a negative cytologic finding in a spiculated lesion (50%). Sampling errors caused by abundant fibrosis, needle deviation, and difficulty in defining the lesion on the stereoscopic views are discussed. Another source of sampling error may be the mixed nature of some lesions consisting of benign and malignant components. Fine-needle aspiration of 219 nonpalpable breast lesions by using a stereotactic localization device yielded representative cytologic samples in 74% of the lesions. PMID- 2110727 TI - Stereotactic fine-needle aspiration biopsy for nonpalpable breast lesions. PMID- 2110728 TI - The value of sonography in the diagnosis of acute diverticulitis of the colon. AB - To assess the value of sonography as the initial imaging procedure in patients suspected of having acute diverticulitis of the colon, we evaluated the sonograms of 71 patients who had clinical signs and symptoms of the disease. Identification of diverticula on sonograms was taken as evidence of acute diverticulitis. Fifty four patients had sonographic findings consistent with this diagnosis. These included gut wall thickening (53), diverticula (34), pericolic (21) and intramural (two) fluid collections, edema of the pericolic fat (22), and intramural sinus tract (one). The final diagnosis was based on the clinical impression (all cases); pathologic interpretation of a surgical specimen (33 cases); findings on contrast enema (40 cases), CT scan (14 cases), and colonoscopy (18 cases); and a favorable clinical outcome in the absence of therapy (17 cases). Forty-six of the 54 patients with positive sonograms had acute diverticulitis, six had pericolic inflammatory masses caused by other colonic diseases, and two had surgically confirmed diverticulosis without active inflammation. All 17 patients with normal sonograms were treated conservatively. Diverticulitis was not confirmed in any of these patients. Our study suggests that sonography is a valuable imaging technique in the patient with signs and symptoms of acute diverticulitis. PMID- 2110729 TI - Common bile duct biopsy with the Simpson atherectomy catheter. PMID- 2110730 TI - Obstructing villous adenoma and papillary adenomatosis of the bile ducts. PMID- 2110731 TI - Combined systemic and portal venous gas: sonographic and CT detection in two cases. PMID- 2110732 TI - Intrarenal arterial Doppler sonography in patients with nonobstructive renal disease: correlation of resistive index with biopsy findings. AB - The resistive index (RI), calculated from the duplex Doppler waveform, was compared with clinical and laboratory findings and the results of renal biopsy in 41 patients with nonobstructive (medical) renal disease. Kidneys with active disease in the tubulointerstitial compartment had a mean RI of 0.75 +/- 0.07. This was statistically significantly different (p less than .01) from the RI in kidneys with disease limited to the glomeruli (mean RI of 0.58 +/- 0.05). Acute tubular necrosis resulted in an elevated RI (mean RI = 0.78 +/- 0.03) as did vasculitis/vasculopathy (mean RI = 0.82 +/- 0.05). Patients with hypertension, proteinuria, or hematuria did not have kidneys with a significantly higher RI than did patients without these clinical factors. Kidneys found to be abnormally echogenic did not have an RI significantly different from kidneys of normal echogenicity. There was a weak correlation between creatinine level and RI value, reflected by a linear correlation coefficient of 0.34. In patients with normal renal RIs, the mean creatinine level was 1.7 +/- 1.7, whereas in those with abnormal RI values (greater than or equal to 0.70), the mean creatinine level was 3.7 +/- 3.6. We conclude that some forms of nonobstructive renal disease can produce changes in the Doppler waveform detectable by RI measurement. The production of Doppler waveform changes is strongly influenced by the site of the main disease within the kidneys. Active disease within the tubulointerstitial compartment (acute tubular necrosis, interstitial nephritis) or vasculitis/vasculopathy generally resulted in an elevated RI, whereas disease limited to the glomeruli, no matter how severe, did not significantly elevate the RI. Degree of renal dysfunction as indicated by serum creatinine level probably affects the Doppler waveform to some degree, but the relationship is weak. PMID- 2110733 TI - Heating of the scrotum by high-field-strength MR imaging. AB - Sterility can occur in mammals if spermatogenic tissue is acutely or chronically heated to levels equal to or greater than body temperature. High-field-strength MR imaging has been shown to elevate tissue temperatures, particularly if high levels of RF radiation are used. To determine if MR imaging above the recommended level for RF radiation is associated with heating of the scrotum, scrotal skin temperatures were measured in eight subjects immediately before and after MR imaging of the scrotum with a 1.5-T, 64-MHz MR scanner at mean whole-body average specific absorption rates ranging from 0.56 to 0.84 W/kg (mean, 0.72 W/kg). The average imaging time was 23 min. A statistically significant (p less than .01) increase in average scrotal skin temperature was associated with MR imaging (before MR imaging, 30.8 degrees C; after MR imaging, 32.3 degrees C). The largest change in temperature was 3.0 degrees C, and the highest temperature measured was 34.1 degrees C. MR imaging at relatively high specific absorption rates produced a statistically significant increase in average scrotal skin temperature. However, the recorded temperatures were below the threshold known to affect spermatogenesis in mammals. PMID- 2110734 TI - Jogging causes acute changes in the knee joint: an MR study in normal volunteers. AB - As MR imaging allows evaluation of soft-tissue structures not previously possible with imaging techniques, we undertook a preliminary study to evaluate the effects of a popular form of exercise (jogging) on the knee. The specific question prompting our investigation was, does repetitive impulse loading produced by jogging cause acute structural changes within the knee that are visible by MR imaging? The knees of 10 healthy subjects were examined on a 1.5-T MR system before and immediately after 30 min of continuous jogging. The same extremity was examined each time, and the imaging sequences and photographic technique (meniscal windows) were identical for both examinations. Effusions developed in five of 10 subjects after exercise. In addition, five of 10 subjects had subtle increased signal intensity within their menisci. These results suggest that jogging frequently leads to acute changes in the knee that are visible on MR imaging. The significance of these changes is unknown. PMID- 2110735 TI - MR imaging of the knee: pseudotear of the lateral meniscus caused by the meniscofemoral ligament. AB - Sagittal MR images of the knee often show a linear band of increased signal in the medial aspect of the posterior horn of the lateral meniscus that can be confused with a meniscal tear. This pseudotear is due to the meniscal insertion of the meniscofemoral ligament. To study the normal appearance of the medial aspect of the posterior horn of the lateral meniscus, we analyzed 109 MR examinations and correlated the findings with the results of arthroscopy. The meniscofemoral ligament was visualized in 54 cases (50%), and in 42 cases (39%) it caused the appearance of a pseudotear on sagittal images. The pseudotear had one of two orientations. The most common (35/42) was an oblique orientation coursing from the superior surface posteriorly and inferiorly. The other (7/42) was a more vertical orientation parallel to the base of the meniscus. Knowledge of the characteristic location and orientation of the meniscofemoral ligament should help to distinguish it from a true meniscal tear on MR images. PMID- 2110736 TI - Intracapsular osteoid osteoma of the proximal femur: findings on plain film and CT. PMID- 2110737 TI - MR imaging of the temporomandibular joint: a cadaver study of the value of coronal images. AB - Recent studies comparing cryosectional anatomy of the temporomandibular joint (TMJ) to its MR appearance have shown that the assessment of disk displacement is inaccurate when based on the sagittal plane alone. This article describes the MR appearance of the normal and abnormal (positional and osseous changes) TMJ in the coronal plane and compares these findings with their cryosectional anatomy. Twenty-two TMJs from unselected frozen cadavers were embedded in paraffin. Coronal and sagittal MR imaging was performed; specimens were then cut in the same plane as the coronal images. Disk position by cryosection was normal in 14 cases and abnormal in eight cases. Coronal MR images alone correctly depicted the TMJ disk position in 17 cases (77%) (13 normal, four abnormal). Complementary sagittal images were necessary for diagnosing anterior displacement in two cases (9%). MR was inaccurate in three cases (14%) of severe degenerative joint disease. Bone condition was correctly diagnosed on the basis of coronal images alone in all cases. Our study shows that coronal MR imaging alone of the TMJ in cadavers accurately shows disk position in 77% of cases. Complementary sagittal images were of benefit in the diagnosis of an additional 9% with anterior displacement. Disk position was assessed inaccurately in either plane in patients with severe degenerative joint disease. For a full MR assessment of the TMJ for disk position and bone condition, we recommend imaging in both coronal and sagittal planes. PMID- 2110739 TI - Arterial embolization to control life-threatening hemorrhage from a Meckel's diverticulum. PMID- 2110738 TI - Staging of Hodgkin disease in children: comparison of CT and lymphography with laparotomy. AB - Proper therapy for Hodgkin disease requires accurate staging of the disease. We compared the value of CT and lymphography with that of laparotomy for staging newly diagnosed Hodgkin disease in 46 children. The laparotomy revealed disease in one or more subdiaphragmatic sites in 46%. Correlation of the imaging studies with the laparotomy findings showed that lymphography has a greater sensitivity (80%) than does CT (40%) in detecting retroperitoneal lymph nodes. The sensitivity of CT in detecting splenic involvement was only 19%, presumably because of the small size of tumor deposits in involved spleens. Staging laparotomy altered the clinical stage in 37% of children, which resulted in a significant change of therapy in those patients. Although lymphography and, to a lesser degree, CT are useful for staging of Hodgkin disease, laparotomy continues to be the most important tool in choosing appropriate therapy for children with Hodgkin disease. PMID- 2110740 TI - Diagnosis of tumors of the parotid gland with anti-CEA immunoscintigraphy. AB - Twenty-nine consecutive patients with a palpable unilateral tumor in the parotid gland region had scintigraphy 22-28 hr after they were injected with 111In labeled monoclonal anti-carcinoembryonic antigen (CEA) antibody (F023C5). Two patients were imaged at 48 hr also, and one patient was imaged additionally with single-photon emission CT. Twenty-seven of the patients had surgery within 2-3 weeks. The serum CEA concentrations were normal in 27 of 29 patients. Immunoglobulin G human anti-murine-antibody concentrations were elevated in three of 20 patients. Ten patients had scintigraphic findings suggesting a malignant tumor, six of them had histologically proved malignant tumors. The tumors associated with positive immunoscintigrams were stained immunohistochemically with anti-CEA, and four of the malignant tumors were positive in immunohistochemical staining. The results suggest that nonspecific anti-CEA antibody imaging is helpful in predicting the presence of a malignant tumor in the parotid area. The radioantibody method could provide useful clinical information that has a high negative predictive value. PMID- 2110741 TI - MR imaging of the cranial nerves. PMID- 2110742 TI - Intracranial chemical-shift artifacts on MR images of the brain: observations and relation to sampling bandwidth. AB - The purpose of this study was to evaluate the presence of chemical-shift artifacts on cranial MR and to illustrate the interrelationship among chemical shift artifacts, variable acquisition parameters, and field strength. Measurements of chemical-shift artifacts were performed on scans obtained from a volunteer imaged in a 1.5-T General Electric system at bandwidths of 8, 16, and 32 kHz, using a 24-cm field of view and an 8-kHz bandwidth with a 48-cm field of view. Chemical-shift displacements at 8 kHz were 6.6 and 14.2 mm at the respective fields of view. Retrospective review was also performed in 77 cases of cranial MR performed on a 1.4-T Technicare unit for the presence and source of chemical-shift artifact on spin-density and T2-weighted images. Most data reviewed showed no significant interference of chemical-shift artifacts on cranial images. An artifactual subdural fluid collection was a common artifact (n = 30/77). When present, this was due to shift of fat signal from subcutaneous tissues onto the brain in patients younger than 10 years old (n = 4/10) and correlated with the distance between brain and subcutaneous fat of less than the linear value of the chemical shift. When this artifact was present in adults (n = 25/67), it was due to shift of the medullary fat signal across the inner table of the skull. The latter also occurred in one child under 10. Apparent location shifts, consistent with the displacement expected from the chemical-shift artifact, were noted in five of five cases of intracranial lipoma. In one of these, the chemical-shift artifact disguised the presence of a large associated vessel. The method of calculating the linear displacement of chemical-shift artifact is reviewed, and the interrelationship of machine parameters and chemical-shift artifact is illustrated. Chemical-shift artifact increases proportionally with field strength and field of view. Increasing the bandwidth to decrease chemical-shift artifact has a resultant penalty in signal to noise but allows a lower time to echo. A lower time to echo can also be accomplished without increasing the bandwidth if asymmetric sampling is used. Awareness of the relationships among chemical-shift artifacts, acquisition parameters, and field strengths can result in a more tailored examination when the chemical-shift artifact is going to be a significant factor. In addition, interpreter error can be avoided by awareness of these relationships when reviewing images from outside institutions. PMID- 2110743 TI - MR signal abnormalities in memory disorder and dementia. AB - MR imaging of the brain, performed in 86 normal subjects and 113 patients with objective memory disorder or dementia, demonstrated white- and gray-matter areas of high signal intensity on long TR images (short and long TE). Hyperintensities were analyzed with respect to size (on a scale of 0-3) and location: lesions were periventricular, subcortical, or cortical. The patients with memory disorder and dementia were categorized as having probable/possible Alzheimer disease, a combination of Alzheimer disease and multiinfarct cognitive disorder, or multiinfarct cognitive disorder alone on the basis of clinically determined Hachinski ischemic scores. Significant correlations were found between age and scores for periventricular lesions (r = .40, p less than .0005) and subcortical lesions (r = .39, p less than .0005) in normal subjects. Correlations were also found between the Hachinski ischemic score and scores for periventricular lesions (r = .21, p less than .01), subcortical lesions (r = .27, p less than .0002), and cortical lesions (r = .32, p less than .0005) in subjects with memory disorder/dementia. Comparing multiinfarct cognitive disorder, Alzheimer disease, and normal groups, the mean scores for periventricular lesions were 12.0 +/- 4.6, 7.6 +/- 4.8, and 3.4 +/- 2.6, while mean scores for subcortical lesions were 10.8 +/- 12.2, 4.1 +/- 6.4, and 0.8 +/- 1.2, respectively. Periventricular lesions were present in 99-100% of patients with Alzheimer disease and multiinfarct cognitive disorder. On the other hand, subcortical lesions, which were identified in 100% of patients with multiinfarct cognitive disorder, were present in only about half of the patients with Alzheimer disease. Thus, scores for both periventricular and subcortical lesions are positively correlated with age and risk factors for cerebrovascular disease and also are significantly increased in the presence of objective memory disorder or dementia. These results imply that in the subject groups considered here, elderly patients with vascular dementia are most likely to have severe white-matter abnormalities on MR scans. The score for subcortical lesions appears to be more helpful than the score for periventricular lesions in distinguishing vascular dementia from Alzheimer disease and normal aging, so that a patient with prominent subcortical white matter abnormalities is more likely to have a diagnosis of vascular than degenerative dementia. PMID- 2110744 TI - Posttraumatic cerebral infarction diagnosed by CT: prevalence, origin, and outcome. AB - Posttraumatic cerebral infarction is a recognized complication of craniocerebral trauma, but its frequency, cause, and influence on mortality are not well defined. To ascertain this information, all cranial CT studies demonstrating posttraumatic cerebral infarction and performed during a 40-month period at our trauma center were reviewed. Posttraumatic cerebral infarction was diagnosed by CT within 24 hr of admission (10 patients) and up to 14 days after admission (mean, 3 days) in 25 (1.9%) of 1332 patients who required cranial CT for trauma during the period. Infarcts, in well-defined arterial distributions, were diagnosed either uni- or bilaterally in the posterior cerebral (17), proximal and/or distal anterior cerebral (11), middle cerebral (11), lenticulostriate/thalamoperforating (nine), anterior choroidal (three), and/or vertebrobasilar (two) territories in 23 patients. Two other patients displayed atypical infarction patterns with sharply marginated cortical and subcortical low densities crossing typical vascular territories. CT findings suggested direct vascular compression due to mass effects from edema, contusion, and intra- or extraaxial hematoma as the cause of infarction in 24 patients; there was postmortem verification in five. In one patient, a skull-base fracture crossing the precavernous carotid canal led to occlusion of the internal carotid artery and ipsilateral cerebral infarction. Mortality in craniocerebral trauma with complicating posttraumatic cerebral infarction, 68% in this series, did not differ significantly from that in craniocerebral trauma patients without posttraumatic cerebral infarction when matched for admission Glasgow Coma Score results. Thus, aggressive management should be considered even in the presence of posttraumatic cerebral infarction. PMID- 2110745 TI - Excretion of gadopentetate dimeglumine in human breast milk. PMID- 2110746 TI - Computerized on-line reporting of coronary angiograms with the CLIP system. PMID- 2110747 TI - Chest case of the day. Tetralogy of Fallot with pulmonary atresia (pseudotruncus arteriosus). PMID- 2110748 TI - Chest case of the day. Metastatic osteosarcoma to lung. PMID- 2110749 TI - Chest case of the day. Traumatic pneumatocele. PMID- 2110750 TI - Abdominal case of the day. Ileocolic intussusception in AIDS. PMID- 2110751 TI - Abdominal case of the day. von Hippel-Lindau disease. PMID- 2110752 TI - Abdominal case of the day. Mesenteric panniculitis. PMID- 2110753 TI - Abdominal case of the day. Malignant extraadrenal retroperitoneal paraganglioma. PMID- 2110754 TI - Musculoskeletal case of the day. Parosteal osteosarcoma of the humerus. PMID- 2110755 TI - Musculoskeletal case of the day. Osseous sarcoidosis and chronic polyarthritis. PMID- 2110756 TI - Musculoskeletal case of the day. Primary oxalosis with renal osteodystrophy. PMID- 2110757 TI - Musculoskeletal case of the day. Gorham syndrome of the right clavicle and scapula. PMID- 2110758 TI - Neuroradiology case of the day. Neurofibromatosis 2. PMID- 2110759 TI - Neuroradiology case of the day. Hypothalamic histiocytosis X. PMID- 2110760 TI - Neuroradiology case of the day. Parasellar epidermoid. PMID- 2110761 TI - Neuroradiology case of the day. Subarachnoid hemorrhage complicating an ependymoma of cauda equina. PMID- 2110762 TI - Universal premedication before use of ionic contrast medium. PMID- 2110763 TI - Reaction to nonionic contrast medium during arthrography of the temporomandibular joint. PMID- 2110764 TI - Heart-lung transplantation: postoperative pleural effusion. PMID- 2110765 TI - Collapse of a breast implant after mammography. PMID- 2110766 TI - Percutaneous intracavitary treatment of a giant aspergilloma. PMID- 2110767 TI - Cocaine-induced small-bowel perforation. PMID- 2110768 TI - The role of imaging in the diagnostic evaluation of impotence. PMID- 2110769 TI - Bilateral dorsal defect of the patella. PMID- 2110770 TI - Agenesis and lipoma of the corpus callosum: MR findings. PMID- 2110771 TI - Standards for color Doppler imaging. PMID- 2110772 TI - Intracaval breakage of a Kimray-Greenfield filter. PMID- 2110773 TI - Maximal dilution of activase. PMID- 2110774 TI - Titrating nitroglycerin. PMID- 2110775 TI - Urea recycling from the renal pelvis in sheep: a study with [14C]urea. AB - To test the hypothesis that urea can be recycled from the renal pelvis, [14C]urea diluted in native urine (1 microCi/ml) was perfused (0.5 ml/min) into one of the pelvises of sheep fed either normal (NP) or low (LP)-protein diets. Blood samples were obtained from the ipsilateral renal vein and from the carotid artery throughout the perfusions. 14C activity determinations in urine and plasma demonstrated a flux of [14C]urea from the pelvis to renal vein blood (40,000 in NP and 130,000 disintegrations/min in LP sheep, P less than 0.01). The corresponding flux of native urea was only 1.5 times higher in NP than in LP sheep (6.8 +/- 1.1 vs. 4.7 +/- 2.9 mumol/min, not significant) despite their 8 times higher urinary concentration of urea. The fraction of filtered urea that was reabsorbed in the pelvis was larger in LP sheep (7.5 +/- 3.7 vs. 1.9 +/- 0.7% in NP sheep, P less than 0.05). A fraction of urea is thus actually recycled from the renal pelvis in sheep, and this pelvic retention is enhanced in LP animals. The importance of this phenomenon in the nitrogen economy is discussed. PMID- 2110776 TI - Cyclooxygenase-dependent mediators of renal hemodynamic function in female rats. AB - Previous studies have revealed a sex-dependent difference in response to cyclooxygenase inhibition in anesthetized male and female rats. Female rats have shown an unexpected vasodilation in response to prostaglandin (PG) inhibition. The present studies were designed to further investigate the sex-dependent role of the PG system in the control of normal renal hemodynamics in female Munich Wistar rats. Renal hemodynamic studies were performed on anesthetized female rats before and during acute cyclooxygenase inhibition using a variety of protocols. One group underwent subacute unilateral renal denervation. A separate group was chronically catheterized and plasma catecholamines were measured during the awake state and then after anesthesia under the euvolemic protocol. Another group was administered the angiotensin II blocker, saralasin, before and during cyclooxygenase inhibition. In a final group, flow to the distal nephron was interrupted via placement of a wax block into the late proximal tubule to determine the role of distal nephron flow and tubuloglomerular feedback in the glomerular response to cyclooxygenase inhibition. It was determined that neither the wax block nor saralasin administration attenuated the vasodilatory response observed in normal female rats due to cyclooxygenase inhibition; however, subacute unilateral renal denervation completely blocked the vasodilatory response to PG inhibition in these female Munich-Wistar rats. Plasma catecholamines were found to be similar whether awake or under anesthesia. These studies indicate the importance of the adrenergic system in modulating PG production in the acutely anesthetized intact female rat. PMID- 2110777 TI - Light-chain binding sites on renal brush-border membranes. AB - Immunoglobulin light chains are low-molecular-weight proteins filtered at the renal glomerulus and catabolized within the proximal tubular epithelium. Excessive production and urinary excretion of light chains are associated with renal dysfunction. They also interfere with proximal renal tubule epithelial functions in vitro. We studied the binding of 125I-labeled kappa- and lambda light chains, obtained from the urine of multiple myeloma patients, to rat and human renal proximal tubular brush-border membranes. Light-chain binding to brush borders was also demonstrated immunologically by flow cytometry. Computer analysis of binding data was consistent with presence of a single class of low affinity, high-capacity, non-cooperative binding sites with relative selectivity for light chains on both rat and human kidney brush-border membranes. The dissociation constants of light chains ranged from 1.6 X 10(-5) to 1.2 X 10(-4) M, and maximum binding capacity ranged from 4.7 +/- 1.3 X 10(-8) to 8.0 +/- 0.9 X 10(-8) (SD) mol/mg protein at 25 degrees C. Kappa- and lambda-light chains competed with each other for binding with comparable affinity constants. Competition by albumin and beta-lactoglobulin, however, was much weaker, suggesting relative site selectivity for light chains. These binding sites probably function as endocytotic receptors for light chains and possibly other low-molecular-weight proteins. PMID- 2110778 TI - Detection of specific mRNAs in single nephron segments by use of the polymerase chain reaction. AB - We have developed a procedure to detect specific mRNAs in single renal nephron segments. This approach combines microdissection, reverse transcription (RT) of the target mRNA, and amplification of the resulting cDNA using the polymerase chain reaction (PCR). After microdissection, the sample is placed in a tube where it is permeabilized and where all reactions are performed directly without the need for isolation of the RNA. Our model target was the mRNA for aldose reductase. This enzyme catalyzes the conversion of glucose to sorbitol. Its expression is modulated by changes in extracellular osmolality in the renal medulla. RT-PCR of inner medullary collecting duct (1 mm) and glomeruli (6-10) yielded a product of the predicted length (670 base pairs) defined by the PCR primers. Its identity was confirmed by a specific oligonucleotide probe that differed from the primers. RT-PCR of proximal tubules (1 mm) resulted in no aldose reductase-specific amplification product. RT-PCR is generally applicable for measuring specific gene expression in single nephron segments or small numbers of cultured cells. Utility, limitations, and refinements of this approach are discussed. PMID- 2110779 TI - Long-term effects of nimodipine on pial microvasculature and systemic circulation in conscious rats. AB - The chronic cranial window preparation allows repeated measurements of the same pial vessels in unanesthetized rats for several weeks and correlation with 24-h monitoring of hemodynamic variables. Nimodipine (20 mg) or placebo was given via two subcutaneous pellets. Large arterioles dilated 26 and 16%, at hour 1 and days 6-13, respectively (P less than 0.02). There was an increase in number of small arterioles throughout the whole observation period with the maximal increment of 47% (P less than 0.05) at days 6-13. Maximal vasodilation with 10% CO2 indicated that the increase in number of small arterioles after administering nimodipine was not caused by the opening of previously closed vessels. The total length of small arterioles and venules increased 47 and 23% at days 6-13, respectively (P less than 0.001). These increases seem to be caused by the increases in the numbers of vessels, because the average length of the small vessels did not appear to change. This suggests that nimodipine reduces cerebral vascular resistance by causing cerebral microvessel neovascularization. Our data demonstrate that the administration of nimodipine (20 mg) is potent in dilating pial arterioles in the short-term without affecting systemic arterial pressure, and that its long-term effect results in new vessel growth. PMID- 2110780 TI - Xanthine oxidase-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. AB - We hypothesized that xanthine oxidase (XO)-derived hydrogen peroxide (H2O2) contributes to ischemic skeletal muscle injury during reperfusion. We found that after ischemia (3 h) and then reperfusion (4 h) rat gastrocnemius muscles had decreased contractile function following direct stimulation. Three lines of investigation suggested that XO-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. First, treatment with dimethylthiurea (DMTU), a highly permeant O2 metabolite scavenger, but not urea, just before reperfusion improved muscle function in legs subjected to ischemia and then reperfusion. Second, gastrocnemius muscles from rats fed tungsten or allopurinol had negligible XO activities and increased muscle function after ischemia and reperfusion. Third, as assessed by measurement of skeletal muscle catalase activity in the presence of aminotriazole, H2O2 was measured during reperfusion of ischemic muscles from untreated or urea-treated rats but not during reperfusion of muscles from rats treated with DMTU, tungsten, or allopurinol. PMID- 2110781 TI - Detergents, dimeric G beta gamma, and eicosanoid pathways to muscarinic atrial K+ channels. AB - Control experiments for the direct effects of G protein beta gamma-subunits (G beta gamma) on muscarinic atrial K+ channel [K+ (ACh)] currents have produced different results (Nature Lond. 327: 21-22, 1987; Nature Lond. 325: 296-297, 1987; Cold Spring Harbor Symp. Quant. Biol. 53: 365-373, 1989). A recent view is that stimulation is indirect via phospholipase by (PLA2) and arachidonic acid (AA) metabolites (Nature Lond. 337: 504-505, 1989). On reexamination we found that 1) the zwitterionic detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1 propanesulfonate (CHAPS) used to suspend beta gamma stimulates atrial K+ (ACh) currents by itself, and the effects are concentration and Mg2+ dependent; 2) CHAPS stimulates atrial ATP-sensitive K+ channel and inwardly rectifying K+ channel currents; 3) blockers of eicosanoid pathways have nonspecific effects on atrial K+, Ca2+, and Na+ channels. We have confirmed that detergent-free, hydrophilic G beta gamma-subunits inhibit K+ (ACh) currents. Stimulatory effects of dimeric G beta gamma could not be separated from stimulatory effects of detergent, and blockers of PLA2 or lipoxygenase pathways do not clearly establish the significance of these pathways to atrial K+ (ACh) currents. PMID- 2110782 TI - Direct observation of the phosphate acceptor and phosphagen pool sizes in vivo. AB - Earthworms were subjected to environmental anoxia (200 min) and electrical stimulation (5 min, 6 V, 50 Hz). The levels of high-energy phosphate compounds and the intracellular pH were monitored during anoxia, muscular contraction, and recovery by in vivo phosphorus-31 nuclear magnetic resonance (31P-NMR). Several key metabolites were determined by enzymatic analysis and reversed-phase high performance liquid chromatography of perchlorate extracts. Because lombricine, the phosphagen phosphate acceptor of earthworms, is a phosphodiester, 31P-NMR permitted direct analysis of the extent of phosphorylation of the lombricine pool in vivo. Total lombricine, lombricine phosphate, ATP, and H+ were measured by NMR, and free ADP was calculated from the lombricine kinase equilibrium constant. The ADP concentration was not significantly changed by anoxia, but it rose threefold after stimulation. L-Lactate accumulated on stimulation, whereas multiple end products (L-lactate, alanine, succinate, and glutamine) were formed during environmental anaerobiosis. PMID- 2110783 TI - Effects of temperature and acid-base state on hippocampal population spikes in hamsters. AB - Previous studies have shown that changes in temperature, within the range encountered by hamsters entering hibernation, alter the evoked response of hippocampal pyramidal cells to stimulation of an afferent pathway. The present study was designed to determine whether these alterations are due to changes in the acid-base status of the neural tissue brought about by changes in temperature. Extracellular-evoked responses were recorded from hamster hippocampal slices after Schaffer collateral stimulation. The pH was changed by varying the concentration of CO2 aerating the bathing medium. Buffers contained either 26 or 40 mM bicarbonate ion. The width of the population spike (the synchronous firing of pyramidal cells) was measured as pH was varied between 7.5 and 7.1, with slice temperature set at either 25 or 20 degrees C. There was a significant increase in spike width as temperature was lowered to 20 degrees C, but no significant change in spike width or amplitude as pH or bicarbonate was varied. The effect of temperature (20 degrees C for half-maximal stimulation, and from 20 to 25 degrees C for just maximal stimulation) on spike width and amplitude thus does not appear to be due to pH- or bicarbonate-induced changes. PMID- 2110784 TI - Renal and systemic hemodynamic responses to sustained submaximal exertion in horses. AB - We investigated the effects of 1 h of sustained submaximal exertion on the renal and systemic hemodynamics of six horses. The horses ran on a treadmill at a speed that produced heart rates of 55-60% of each horse's maximum heart rate. Exertion produced heart rates of 121 +/- 6.6 and 126 +/- 6.1 (SE) beats/min after 15 and 60 min, respectively. Cardiac output increased significantly (P less than 0.05) from 70.1 +/- 3.1 to 246.2 +/- 4.7 ml.min-1.kg body wt-1 after 15 min of exertion and thereafter did not change. There was no significant change from rest in p aminohippuric acid and creatinine clearances, filtration fraction, or renal blood flow during exertion. Plasma total solid concentration and hematocrit increased by 3.8 and 8.6%, respectively, between 20 and 60 min of exertion. Pulmonary artery temperature increased significantly from 37.6 degrees C at rest to 38.6 degrees C at 60 min of exertion. This study demonstrates the ability of the horse to maintain renal hemodynamics similar to resting values and systemic hemodynamics at steady-state values despite hemoconcentration and increased body temperature during sustained submaximal exertion. PMID- 2110785 TI - Olfactory receptor response to CO2 in bullfrogs. AB - In vivo electrophysiological recordings of olfactory receptor cells of the bullfrog (Rana catesbeiana) exhibit a receptor response to CO2 concentrations as low as 0.5%. The amplitude of the electroolfactogram (EOG) increased with an increase in the CO2 concentration delivered to the olfactory epithelium. Likewise, there was a significant increase in the decay time (time from 90 to 10% peak EOG amplitude) with an increase in CO2. The EOG rise time (time from 10 to 90% peak EOG amplitude) and the EOG response latency (time from beginning of CO2 pulse to beginning of EOG response) significantly decreased, whereas the plateau time (time from 90% rising phase to 90% falling phase of the peak EOG amplitude) was not significantly altered by an increase in CO2. These results indicate that low concentrations of CO2, below normal end expiratory CO2 concentrations, stimulate olfactory receptor cells. These results support our proposal that the ventilatory depression observed in response to upper airway CO2 in reptiles and amphibians is mediated by CO2-sensitive olfactory receptor cells. PMID- 2110786 TI - Cell volume regulation by skate erythrocytes: role of potassium. AB - The role of K transport during cell volume regulation in response to extracellular osmolality, protein kinase C activation, and cellular Ca was examined in skate (Raja erinacea) red blood cells (RBC). Reduction of medium osmolality from 960 to 660 mosmol/kgH2O had no effect on K uptake or efflux despite a 25% increase in cell volume. Further reduction to 460 mosmol/kgH2O caused K uptake to double and K efflux to triple resulting in net K loss. Net K efflux in 460 mosmol/kgH2O medium was correlated with the presence of a regulatory volume decrease, which was sensitive to the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and insensitive to chloride replacement. K-K exchange was absent in both isotonic and hypotonic media. Treatment with the Ca ionophore A23187 in the presence of Ca had no effect on either cell volume or K efflux in isotonic medium, indicating the absence of Ca-activated K transport. In contrast, phorbol ester treatment caused cell volume, Na content, and proton and K efflux to increase. Consistent with activation of Na-H exchange, phorbol ester effects were inhibited by dimethylamiloride. This study constitutes the first demonstration of volume sensitive K transport in RBC from the most primitive vertebrate studied to date. PMID- 2110787 TI - Effect of premedication on arterial blood gases prior to cardiac surgery. AB - The effect of premedication on arterial blood gas tensions was studied in thirty adult surgical patients with valvular disease. They were divided into three groups, each group having a different premedication regimen. Blood gas tensions were compared in these patients when awake on the night before surgery, asleep, after premedication and just prior to induction of anaesthesia. Samples were taken while the patient breathed air and each patient acted as his/her own control. The patients were randomised into one of three premedication regimens: 1. intramuscular lorazepam, 2. intramuscular morphine and hyoscine (scopolamine) and 3. oral lorazepam plus intramuscular morphine and hyoscine. There was a statistically significant though not clinically significant rise in PaCO2 and fall in pH following premedication with lorazepam, morphine and hyoscine. There was also a significant fall in PaO2 associated with morphine and hyoscine premedication which was greater than that which occurred with unsedated sleep. Patients who are to undergo cardiac valvular surgery should receive supplementary oxygen following premedication and during transfer to the operating room. PMID- 2110788 TI - Double-blind study of the reversal of midazolam-induced sedation in the intensive care unit with flumazenil (Ro 15-1788): effect on weaning from ventilation. AB - Midazolam (0.1-0.2 mg/kg/hr) and morphine (2 mg/hr) were given by carefully regulated continuous intravenous infusions to thirty patients who required sedation, analgesia and ventilation for between twelve and twenty-four hours in the Intensive Care Unit. The midazolam and morphine infusions were stopped at the end of the period of sedation required and the efficacy of placebo of flumazenil in reversing the sedative effects of midazolam was compared in this double-blind randomised parallel group study. Patients receiving flumazenil were less sedated (P less than 0.05), able to obey commands (P less than 0.05), weaned from ventilation (P less than 0.05) and extubated (P less than 0.05) significantly earlier than those receiving placebo. PMID- 2110789 TI - Nosocomial infection rates during a one-year period in a nursing home care unit of a Veterans Administration hospital. AB - Infections in long-term care institutions are a constant source of morbidity in residents in these facilities. We report our experience with infection rates during a 1-year surveillance period in a 120-bed nursing home care unit of a Veterans Administration hospital. Our purpose was (1) to establish our own infection rate and (2) to ascertain the relationships (a) between infection rate and level of required nursing care and (b) between infection rate and staffing adequacy. Our overall nosocomial infection rate for 1987 was 4.6 infections/1000 patient days. The majority of infections were urinary tract infections, with the predominant pathogen Proteus mirabilis. One ward in the nursing home care unit had a significantly higher infection rate compared with that of the other wards (p less than 0.05), and there was a significantly higher infection rate in residents who required total nursing care versus less dependent residents (p less than 0.05). We were unable to find a direct relationship between the degree of staff shortages and infection rate. This prolonged infection control surveillance indicated our nosocomial infection rates were similar to those in previously published reports. We also identified problem infections in certain areas, which led us to develop staff in-service programs to address these problems. In summary, we believe this information is useful not only for us but for others involved in the care of residents in long-term care facilities inasmuch as there are little published data on yearly infection rates per patient days. PMID- 2110790 TI - APIC guideline for selection and use of disinfectants. PMID- 2110791 TI - Influence of recombinant bovine interferon gamma and dexamethasone on pneumonia attributable to Haemophilus somnus in calves. AB - The influence of recombinant bovine interferon gamma (rBoIFN-gamma) treatment on resistance of clinically normal and dexamethasone-treated calves to Haemophilus somnus infection was evaluated. Four groups of 6 calves each were treated with saline solution (controls), dexamethasone (0.04 mg/kg of body weight/for 3 days), rBoIFN-gamma (2 micrograms/kg for 2 days), or dexamethasone and rBoIFN-gamma (aforementioned dosages). All treatments were started 24 hours before intrabronchial challenge exposure with 5 x 10(9) colony-forming units of H somnus. Rectal temperature and WBC count were monitored daily. Two of the dexamethasone-treated calves died of pneumonia 4 days after challenge exposure and were necropsied. All other calves were euthanatized and necropsied 7 days after challenge exposure. All calves had pneumonia of variable intensity. Dexamethasone-treated calves had increased volume of pneumonic lung (P less than 0.05) and increased severity of pneumonia, compared with control calves. Recombinant bovine interferon gamma treatment resulted in reduction in pneumonic lung volume and severity of pneumonia in dexamethasone-treated calves (P less than 0.05), although it did not influence severity of pneumonia in nondexamethasone-treated calves. PMID- 2110792 TI - Is solo practice really dead? AB - For years, the demise of solo practice has been predicted as a consequence of the corporatization of health care, the rise of managed care programs, and the creation of preferred provider organizations (PPOs). The predictors of the demise are leaders in the health maintenance organization (HMO) and PPO movement and therefore have much to gain if solo practice dries up. A survey of a random sample of licensed psychologists in New Jersey was conducted to determine the current state of private practice. A 58% return of the anonymous questionnaire revealed that 87% were in solo practice; 90% were not members of any PPO; 92% received either no referrals or less than 5% from HMOs; and 92% indicated that their referral rates and practices have either stayed the same or increased in the past three years. Clearly the predictions as far as New Jersey goes are wrong! The findings are discussed in terms of economics, humanistic concerns, and political concerns. PMID- 2110793 TI - Growth hormone-releasing factor and feeding. Behavioral evidence for direct central actions. PMID- 2110794 TI - Regulation of human lung fibroblast collagen production by recombinant interleukin-1, tumor necrosis factor, and interferon-gamma. AB - Several cytokines have been shown to modulate the synthesis of matrix molecules, but few reports have defined how the cytokines interact with one another in mediating these regulatory effects. To define the cytokine network regulating collagen production, we have studied the effects of interferon-gamma, interleukin 1, and tumor necrosis factor on collagen synthesis by cultured human lung fibroblasts. Confluent cells were treated with cytokines for 24 h in the absence of serum or in media containing 1% serum. In the absence of serum, IL-1 and TNF each dose-dependently stimulated types I and III collagen production, with a maximal 2-4-fold increase in collagen accumulation being observed. Cells treated with IL-1 and TNF in combination showed less stimulation than with either cytokine alone. IFN-gamma also diminished the stimulatory effects of both IL-1 and TNF. In contrast, in 1% serum IL-1 and TNF individually had relatively minor effects, while IFN-gamma inhibited collagen production. However, the combination of IL-1 and TNF inhibited collagen production. Generally, these effects were achieved through control of mRNA levels. These studies demonstrate the existence of a cytokine network regulating fibroblast collagen production and suggest that cytokine effects in vivo may vary depending upon the constellation of factors present in the tissue. PMID- 2110795 TI - Structure and function of the laminin-nidogen complex. PMID- 2110796 TI - Distortion product emissions in humans. II. Relations to acoustic immittance and stimulus frequency and spontaneous otoacoustic emissions in normally hearing subjects. AB - Multifrequency and multicomponent evaluations of aural acoustic immittance, including tympanometry and acoustic reflex testing, were performed on 44 normal ears to examine the influence of middle ear functioning on the generation and detection of distortion product otoacoustic emissions (DPEs). In the same ears, the prevalence and parametric features of spontaneous and stimulus frequency emissions were also assessed so that their relationship to the detection "thresholds" and amplitudes of corresponding DPEs could be determined. The general outcome was that none of the examined features of acoustic immittance provided an explanation for the discrete, low-amplitude DPE regions observed in about one third of normal ears. Moreover, the presence of typical spontaneous and stimulus frequency emissions in these same "irregular" ears indicated that emission generation and reverse cochlear transmission were also operating normally within these regions of reduced DPEs. Consequently, other, as yet undetermined influences appear to contribute to the DPE variability noted in some ears. Finally, the simultaneous presence of stimulus frequency emissions, but not spontaneous emissions, appeared to reduce the detection "thresholds" and increase the amplitudes of low-frequency DPEs. PMID- 2110797 TI - Distortion product emissions in humans. I. Basic properties in normally hearing subjects. AB - Distortion product otoacoustic emissions (DPEs) at the 2f1-f2 frequency were recorded from 44 normal ears in response to equilevel primary tones. Detailed testing included the recording of DPE "audiograms" in 100-Hz steps from 1 to 8 kHz at three primary-tone levels (65, 75, and 85 dB sound pressure level [SPL]). In addition, response-growth or input-output (I/O) functions depicting the relationship of the amplitudes of DPEs to primary-tone levels, ranging from 25 to 85 dB SPL in 5-dB steps, were also tested for 11 frequencies distributed at quarter-octave intervals over the identical frequency range. The average DPE "audiogram" illustrating the frequency response of these emissions demonstrated a bilobed contour having a low-frequency maximum at approximately 1.5 kHz and a high-frequency peak that plateaued at about 5.5 kHz. The two maximum regions were separated by a minimum around 2.5 kHz. Depending on the frequency region, the average I/O functions exhibited detection "thresholds" at 3 dB above the noise floor at primary levels between 35 and 45 dB sound pressure level. The dynamic range of the emitted response between detection "threshold" and maximum amplitude varied over a 40-dB extent of the stimulus-level dimension. Approximately one third of the ears exhibited irregular DPE "audiograms" in which emitted responses were significantly reduced in restricted regions tested by low, medium, or high frequencies. When the 44 ears were separated into two groups representing more normal and less-normal responses, the irregular "normal" ears demonstrated increased variability, especially in high-frequency regions. Mean age did not explain the differences noted between the two types of normally hearing subjects. However, across ears, DPE amplitudes and "thresholds" for the highest frequencies tested were correlated significantly with age in that the oldest individuals showed higher "thresholds" and lower amplitudes. PMID- 2110798 TI - Distortion product emissions in humans. III. Influence of sensorineural hearing loss. AB - The realization that otoacoustic emissions are sensitive to cochlear disorders has resulted in the speculation that they may have considerable clinical potential as objective measures of hearing. To assess the clinical utility of one type of emission, the distortion product emission (DPE), a study was undertaken in individuals with hearing impairments representing a number of common otologic disorders. The results of this investigation provided evidence that tests of DPEs promise to satisfy a number of requirements important to clinical testing, including objectivity of measurement procedures, test-retest reliability, simple subject preparation, readily available instrumentation, and relatively brief examination periods. The fine resolution of DPEs within the stimulus frequency and level domains also permits an accurate confirmation of the pattern of hearing loss. For example, tests of DPEs detected a 20-dB hearing level impairment at a single frequency in an ear exhibiting early signs of noise-induced hearing loss, and a 10-dB improvement in sensitivity following ingestion of the hyperosmotic agent glycerol in an ear displaying a mild to moderate hearing loss due to Meniere's disease. Finally, the application of DPEs to the objective testing of otologic disorders suggests that the ability of these responses to assess the sensory component of a sensorineural disorder may contribute to the eventual understanding of the complicated pathogenesis of many cochlear diseases. When all the positive features of DPE testing are realized, the potential contribution that these measures can make in a clinical setting becomes apparent. PMID- 2110799 TI - Interferon-gamma alters expression of endothelial cell-surface glycosphingolipids. AB - Our previous work on human endothelial cell (EC) glycosphingolipids (GSLs) demonstrated that these cells contain a large diversity of GSLs, predominantly with lacto core structures. In order to evaluate the role of GSLs as EC antigens and receptors, we investigated their cell-surface expression on confluent EC monolayers and ECs activated by interferon-gamma (IFN-gamma) and interleukin-1 (IL-1). IFN-gamma activation of endothelial cells resulted in a small change in GSL composition, but greatly increased surface expression of gangliosides and decreased surface expression of neutral GSLs. In particular, surface expression of the major neutral GSL, globoside, decreased three- to fourfold as measured both by galactose oxidase labeling and by binding of the anti-globoside monoclonal antibody 9G7. IFN-gamma did not significantly alter the total cell content of globoside, as measured by metabolic labeling, but rather altered the ratio of accessible cell surface to intracellular globoside. Two mechanisms appear to contribute to the decreased cell-surface globoside expression. IFN gamma treatment increased the relative proportion of intracellular globoside which is associated with the cell cytoskeleton. IFN-gamma treatment also caused more of the cell-surface globoside to be inaccessible to antibody, and both neuraminidase and trypsin treatment of the cells increased globoside accessibility. IL-1 treatment increased total cell GSL content, but did not alter GSL composition or cell-surface binding by six anti-carbohydrate antibodies. The specific modulation of cell-surface GSLs by IFN-gamma suggests that GSLs may play a role in the altered adhesive and receptor activities of IFN-gamma-activated ECs. PMID- 2110800 TI - Formation of diastereoisomeric 3a-hydroxypyrroloindoles from a tryptophan residue analog mediated by iron (II)-EDTA and L-ascorbate. AB - Oxygenation of a tryptophan residue analog by ascorbate in the presence of catalytic amounts of iron(II) and ethylenediaminetetraacetic acid (EDTA) has been studied. Under physiological conditions, reaction of the tryptophan derivative (N t-butoxycarbonyl-L-tryptophan) with Fe(II)-EDTA and ascorbate resulted mainly in the oxygenation of the indole moiety of the substrate. In this reaction, cis and trans diastereoisomeric alcohols 3a-hydroxy-1-t-butoxycarbonyl-1,2,3,3a,8,8a hexahydropyrrolo[2,3- b]indoles have been successfully identified in the metal catalyzed free radical oxidation of indole compounds. Hydroxylation at C-5 and C 6 and a ring opening reaction between C-2 and C-3 have also been confirmed. The reaction of Fe(II)-EDTA/ascorbate with the tryptophan derivative was apparently nonselective with regard to position and was significantly suppressed by the hydroxyl radical scavengers (mannitol and dimethylsulfoxide), suggesting the participation of the hydroxyl radical as the actual oxidizing species. PMID- 2110801 TI - Inhibition of platelet aggregation by S-(1,2-dicarboxyethyl)glutathione, intrinsic tripeptide in liver, heart, and lens. AB - S-(1,2-Dicarboxyethyl)glutathione (DCE-GS) found in animal tissues or baker's yeast showed strong inhibitory effects on blood coagulation and platelet aggregation. The inhibitory effect of blood coagulation was almost the same as those of EDTA, oxalate, and citrate. DCE-GS did not show chelating activity. As for ADP- or thrombin-induced platelet aggregations, DCE-GS exerted a potent effect on the secondary aggregation, while it was less active in the primary aggregation. DCE-GS gave a distinct lag period in the time course of the secondary aggregation induced by collagen and inhibited most strongly the aggregation induced by arachidonic acid compared with those elicited by ADP, thrombin, and collagen. The peptide, however, did not inhibit the platelet aggregation induced by 12-O-tetradecanoylphorbol-13-acetate. Although both DCE-GS and EDTA inhibited the platelet aggregation which was triggered by ADP, their inhibitory manners were entirely different. PMID- 2110802 TI - Transcutaneous carbon dioxide monitoring. PMID- 2110803 TI - Calcium and phosphorus solubility in neonatal intravenous feeding solutions. AB - The limited solubility of calcium and phosphorus in standard parenteral nutrition formulations has restricted the ability to provide sufficient minerals to preterm infants to prevent substrate deficient metabolic bone disease. We determined the solubility limits of calcium and phosphorus in a total of 160 formulations under carefully controlled conditions. By increasing the concentrations of dextrose, amino acids, and by using Addiphos instead of 8.7% dipotassium hydrogen phosphate as the phosphorus source, higher concentrations of both calcium and phosphorus were held in solution. This should permit the delivery of increased concentrations of these minerals at rates which approximate fetal accretion. PMID- 2110804 TI - Acid-base state of the preterm infant and the formulation of intravenous feeding solutions. AB - An acidic intravenous source of phosphorus (Addiphos) was compared with dipotassium hydrogen phosphate in 25 preterm infants to study acid-base state. Eight infants were given either Addiphos or dipotassium hydrogen phosphate alternately for 48 hour periods and similar amounts of calcium and phosphorus were delivered. There were no significant differences in calcium and phosphorus intake, calcium and phosphate plasma concentrations, or acid-base state between study periods on the two solutions. Seventeen infants were given the two solutions alternately for 72 hour periods; Addiphos was used to increase the amounts of calcium and phosphorus being delivered. Calcium and phosphorus intake was decreased on dipotassium hydrogen phosphate, but Addiphos significantly increased calcium and phosphorus intake and plasma calcium and phosphate concentrations. It also lowered the pH of the urine and raised the titratable acidity. Acid-base state, however, was not significantly different. It is therefore possible to increase intake of calcium and phosphorus in preterm infants without causing a significant metabolic acidosis. PMID- 2110805 TI - Rh haemolytic disease: continuing problem of management. AB - Eighteen patients with severe Rh haemolytic disease, all of whom underwent fetal blood sampling and intrauterine transfusion, were studied. Twelve babies survived (67%) all of whom were delivered by lower segment caesarean section. There were three intrauterine deaths resulting in late abortion, one stillbirth with trisomy 21, and two neonatal deaths (both from severe prematurity). The traditional prognostic indicators were all inaccurate, and fetal blood sampling and measurement of the fetal packed cell volume were the most direct methods of assessing haemolysis. The progression of severe Rh disease is unpredictable, and we believe that all cases should be referred to specialist centres for advice or treatment. PMID- 2110806 TI - [Penicillin-binding proteins of various strains of Lactobacillus]. AB - Sensitivity of different species of Lactobacillus i.e. L. casei, L. plantarum, L. acidophillus, L. buchneri, L. jugurti and others to penicillins and cephalosporins of various generations was studied. Penicillin binding proteins (PBPs) of the Lactobacillus species were specified. It was shown that the number of PBPs depended on the Lactobacillus species. L. casei had the least number of PBPs (4) and L. brevis had the highest number of PBPs (11). Competition of 14C benzylpenicillin with ampicillin, cefotaxime, ceftizoxime and cefoperazone for binding to separate PBPs in three strains of different Lactobacillus species was investigated. PMID- 2110807 TI - The Bacillus subtilis menCD promoter is responsive to extracellular pH. AB - Activation kinetics of a Bacillus subtilis menaquinone biosynthetic gene promoter (the menCD promoter) were measured during growth and sporulation, with the aid of a menCD'-lacZ translational gene fusion. Transient maximal activation was seen shortly after the end of exponential growth in unbuffered complex medium containing a low glucose concentration. These activation kinetics were correlated with transient acidification of the medium under conditions permitting TCA cycle function during the post-exponential period, while mutations that blocked TCA cycle function (cit mutants) were associated with sustained acidification and promoter activation during this period. In cit+ strains, buffering of the medium to pH 5.7 caused sustained maximal activation, while buffering to pH 7.2 prevented enhancement of activation. The menCD promoter appears to be responsive to extracellular acidic pH. PMID- 2110808 TI - Blood flow velocity in the middle cerebral artery during carotid cross-clamping: loss of regulatory response to carbon dioxide partial pressure. A transcranial Doppler intraoperative study. AB - The CO2 reactivity of blood flow velocity in the Middle Cerebral Artery (MCA) was explored by Doppler ultrasound, in nine patients, at the time of common carotid artery cross-clamping during vascular surgery, in order to detect if a regulatory response apply during operative occlusion of common carotid artery. Transcranial Doppler was used to monitor ipsilateral MCA blood velocity during carotid surgery. MCA velocity, arterial blood pressure and pCO2 (arterial or end-tidal) were measured, during carotid cross clamping, before and after an increase in pCO2 was induced by changing respiratory rate and volumes. No relevant changes in MCA flow velocities were detected in patients with stable arterial blood pressure. In those patients showing an increase in blood pressure during the surgical procedure the MCA velocity increased accordingly. It is suggested that the cross-clamping of common carotid artery is a critical condition in which no regulatory response can be elicited: blood flow velocity tends to parallel the perfusion pressure and also CO2 reactivity is lost. PMID- 2110809 TI - Plasminogen activator activity of normal and retinoic acid-treated post implantation embryos. AB - Urokinase-type plasminogen activator (uPA) has been implicated in cellular migration accompanying different biological phenomena including organogenesis. An increase in uPA activity was observed in mouse post-implantation embryos during the early organogenesis period. Since we have previously shown that all-trans retinoic acid (RA) prevented the induction of uPA in mouse peritoneal macrophages, we have now assessed whether teratogenic doses of this agent could also interfere with uPA activity in mouse embryo in vitro and in vivo. Post implantation embryos (8.5 days) were incubated for up to 24 hr with micromolar concentration of RA resulting in the occurrence of malformations. No significant difference in uPA activity was found between control and treated embryos. Likewise, uPA activity was not altered in embryos explanted on day 9.5 from dams treated 24 hr before with a teratogenic dose of RA. This study indicates that the teratogenic activity of RA is not caused by an inhibition of the induction of uPA in embryos. PMID- 2110810 TI - [Water-electrolyte and acid-base disorders. V. Acid-base balance]. AB - Disturbances of acid-base homeostasis are frequently associated with many commonly observed disease states. Recognition of abnormal plasma acid-base composition may often direct the clinician to the diagnosis of a specific disease. Simply stated, external hydrogen ion balance exits when the net hydrogen ion production from cellular metabolism equals the net hydrogen ion excretion from the body. Net cellular production of hydrogen ions consist of two components: carbonic acid, which is excreted by the lungs as CO2, and fixed acids, which require renal excretion. The net amount of fixed acid production is determined by cellular metabolism, dietary intake and gut absorption of available base equivalents. The immediate defense of pH is provided by the buffering systems, which also act as transporters of the acid from sites of production to sites of elimination. CO2 exchange by the lungs is responsible for the bulk of acid excretion: more than 99.5 percent of the normal daily acid load and 100 percent of CO2 produced by metabolism are eliminated by this route. On the other hand, the kidney is the only organ capable of excreting an appreciable quantity of fixed acid as titratable acids an ammonium, with the regeneration of bicarbonate buffer. Acid-base; buffering systems; acid-base regulation. PMID- 2110811 TI - Physiology and genetics of methylotrophic bacteria. AB - Methylotrophic bacteria comprise a broad range of obligate aerobic microorganisms, which are able to proliferate on (a number of) compounds lacking carbon-carbon bonds. This contribution will essentially be limited to those organisms that are able to utilize methanol and will cover the physiological, biochemical and genetic aspects of this still diverse group of organisms. In recent years much progress has been made in the biochemical and genetic characterization of pathways and the knowledge of specific reactions involved in methanol catabolism. Only a few of the genetic loci hitherto found have been matched by biochemical experiments through the isolation or demonstration of specific gene products. Conversely, several factors have been identified by biochemical means and were shown to be involved in the methanol dehydrogenase reaction or subsequent electron transfer. For the majority of these components, their genetic loci are unknown. A comprehensive treatise on the regulation and molecular mechanism of methanol oxidation is therefore presented, followed by the data that have become available through the use of genetic analysis. The assemblage of methanol dehydrogenase enzyme, the role of pyrrolo-quinoline quinone, the involvement of accessory factors, the evident translocation of all these components to the periplasm and the dedicated link to the electron transport chain are now accepted and well studied phenomena in a few selected facultative methylotrophs. Metabolic regulation of gene expression, efficiency of energy conservation and the question whether universal rules apply to methylotrophs in general, have so far been given less attention. In order to expand these studies to less well known methylotrophic species initial results concerning such area as genetic mapping, the molecular characterization of specific genes and extrachromosomal genetics will also pass in review. PMID- 2110812 TI - [Effect of NIK-242 inj. (20% erythritol) on intracranial pressure in dogs with acute obstructive hydrocephalus]. AB - The effects of NIK-242 inj. (20% erythritol) on intracranial pressure (ICP) and serum osmotic pressure (Osm. P) were investigated in dogs with acute obstructive hydrocephalus, and they were compared with those of 20% mannitol or 10% glycerol in 5% fructose and 0.9% saline. Animals were divided into 5 groups (n = 6 in each group) and treated with either NIK-242 inj. (0.5 g/kg, 1.0 g/kg, 2.0 g/kg), mannitol (1.0 g/kg) or glycerol (0.5 g/kg). These drugs were administrated intravenously for 10 min. NIK-242 inj. rapidly reduced ICP and increased Osm. P. There was correlation between changes of ICP and Osm. P. The regression equation was Y = -6.489 X + 726.206 (n = 104, p less than 0.00001, R = -0.655). The effects were dose-dependent, but there were no significant differences between the effects of NIK-242 inj. 1.0 g/kg infusion and 2.0 g/kg infusion. The most appropriate dose of NIK-242 inj. was 1.0 g/kg, in which group ICP was significantly lower than the initial pressure until 120 minutes after administration (p less than 0.05). The maximum reduction rate of ICP [(initial ICP-minimum ICP)/initial ICP X 100] was 83.6 +/- 10.6% at 22.7 +/- 3.0 min. after administration. It was 61.6 +/- 6.9% at 19.3 +/- 1.6 min. in mannitol group and 77.1 +/- 7.4% at 15.0 +/- 0.8 min. in glycerol group. There was no rebound phenomenon on ICP during 150 min., but there was one in mannitol group and five in glycerol group. NIK-242 inj.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110813 TI - In vitro beta 2-microglobulin (beta 2m) secretion by normal and leukaemic B cells: effects of recombinant cytokines and evidence for a differential response to the combined stimulus of phorbol ester and calcium ionophore. AB - Due to the increasing therapeutic use of immunoregulatory agents and the potential effects on cellular function, we examined the modulation of in vitro beta 2-microglobulin (beta 2m) production rates by 'normal' tonsil and leukaemic B-cells in response to a number of these agents. Tonsil B-cells responded to phorbol ester (TPA) by an increased beta 2m production rate, which was further enhanced by the combined stimuli of TPA plus the calcium ionophore A23187. In marked contrast, however, lymphocytes from a majority (8/11) of B-cell malignancies showed a suppression of the TPA-induced beta 2m production rate in response to the combined TPA/A23187 stimulus. These different responses of 'normal' and malignant B-cells were not apparent when IgM production rates were examined. The recombinant cytokines IL-1, IL-2, IFN-alpha, IFN-gamma and TNF also enhanced beta 2m production rates of both normal and leukaemic B-cells, but to a considerably lesser extent than did TPA. Bryostatin-1 increased beta 2m production to a level intermediate between that obtained by TPA and the cytokines. It is suggested that beta 2m production rates may correspond to the degree of B-cell differentiation, and/or to the degree of cellular 'activation'. The results further indicate that the in vitro measurement of beta 2m production provides a different index of the cellular response than that obtained by the conventional measurement of IgM production. PMID- 2110814 TI - Bioreductive drugs and the selective induction of tumour hypoxia. AB - In this work tumour hypoxia is induced by physically occluding the tumour vascular supply by clamping, or by giving mice 5 mg kg-1 hydralazine. These methods have previously been shown to increase the radiobiological hypoxic fraction in tumours close to 100%. Their effectiveness in potentiating the bioreductive toxicity of: misonidazole (800 mg kg-1), RSU1069 (80 mg kg-1), mitomycin C (5 mg kg-1) and SR4233 (50 mg kg-1) is assessed in the RIF-1 and KHT tumours using regrowth delay as an assay. Clamping alone for 120 min gives little or no response, but when RSU1069 is administered 15 min before clamping, large growth delays result. RIF-1 tumours clamped for 90 or 120 min with RSU1069 give cure rates of 12.5% and 37.5% respectively. Less effect with clamping is seen for the other bioreductive agents. The effect of hydralazine with RSU1069 although significant in the RIF-1 tumour, is modest compared to that for clamping. Small enhancements of toxicity are seen with hydralazine in combination with misonidazole in the RIF-1 tumour and mitomycin C in both tumours. The varying effectiveness of these treatments is attributed to several factors which include the level and duration of hypoxia, concentration and contact time of the bioreductive drugs, the microenvironment of the tumour and the nature of the reductive metabolic pathways available in the different tumour cell types. PMID- 2110815 TI - The effects of three bioreductive drugs (mitomycin C, RSU-1069 and SR4233) on cell lines selected for their sensitivity to mitomycin C or ionising radiation. AB - We have investigated the cross-sensitivity of a number of cell lines to three different classes of bioreductive drugs under both aerobic and hypoxic conditions. The cell lines used were selected for their sensitivity to DNA damaging agents and fall into two groups. One group, MMC cells derived from CHO K1 cells (Robson et al., 1985), show a range of sensitivities to mitomycin C in air. The second group, irs cells were cloned from V79 Chinese hamster fibroblasts (Jones et al., 1987) and exhibit sensitivity to ionising radiation. The sensitivity of both groups of cells to mitomycin C (MMC), RSU-1069 and SR4233 was assessed under aerobic and hypoxic conditions. No difference in aerobic or hypoxic toxicity of MMC was observed for CHO-K1 or MMC sensitive cell lines (MMC 2 and MMC-3). However, the MMC-resistant cell line (MMCr) was 10 times more sensitive under hypoxic than aerobic conditions. This suggests that MMCr cells lack or are deficient in the enzymes responsible for activating MMC under aerobic conditions compared to other MMC cells. In contrast, differential toxicities of between 3 and 30 have been observed for all CHO cells treated with RSU-1069 and SR4233. Treatment of V79 and irs cells with RSU-1069 and SR4233 also resulted in selective toxicity towards hypoxic cells. Differential toxicities between 50 and 100 were observed for V79 cells. For both RSU-1069 and SR4233, the hypoxic toxicities were similar in V79 and irs cells but in air, the radiation sensitive cells were up to 10 times more sensitive than wild type cells. PMID- 2110816 TI - Epidermal adenylate cyclase system is regulated by diacylglycerol-protein kinase C signal, but not by calcium signal. AB - The breakdown of inositol phospholipids is an important transmembrane signalling system that is composed of two kinds of signals: the diacylglycerol-protein kinase C signal, and the inositol trisphosphate-Ca2+ signal. Using membrane permeable diacylglycerol, I-oleoyl-2-acetylglycerol (OAG), and calcium ionophore, A-23187, the effects of these chemicals on the epidermal adenylate cyclase system were investigated. OAG increased forskolin- and cholera toxin-induced cyclic AMP accumulations, but receptor adenylate cyclase responses were markedly decreased by treatment with OAG. The effects of OAG were inhibited by the protein kinase C inhibitor, H-7. Calcium ionophore, A-23187, had no effect on the epidermal adenylate cyclase responses. Combinations of OAG and A-23187 (as well as the calcium chelator, EGTA), showed that the action of OAG was mostly unaffected by the modulation of intracellular and extracellular Ca2+ concentrations. The results suggest that among the signals triggered by the breakdown of inositol phospholipids, only diacylglycerol-protein kinase C signal is involved in the regulation of the epidermal adenylate cyclase system. PMID- 2110817 TI - The antipruritic effect of a sedative and a non-sedative antihistamine in atopic dermatitis. AB - A double-blind, randomized, cross-over study was carried out on the effect of a sedative and a non-sedative antihistamine on 25 adults with atopic dermatitis. Intensity of itch was recorded using a computerized method for self-assessment (Pain-Track) and using conventional visual analogue scales. The antipruritic effect of 3 days of treatment with the non-sedative H1 antagonist terfenadine (60 mg b.i.d.) and with the sedative antihistamine, clemastine (2 mg b.i.d.) did not differ from that found with the placebo. Our findings support the view that histamine is not of importance in the pathogenesis of itch in atopic dermatitis. PMID- 2110818 TI - Management of upper airway obstruction in the Pierre Robin syndrome. AB - Eight patients with Pierre Robin syndrome (PRS), were treated according to our management protocol. All our patients initially were given a trial of conservative, positional treatment, with high caloric gavage feeding. In five patients this therapeutic approach resulted in a good weight gain, with no significant respiratory distress. The remaining three patients showed no improvement, failed to thrive and therefore underwent the tongue to lip adhesion (TLA) procedure. Two patients then improved dramatically; whereas one continued with respiratory distress and failure to thrive and required tracheostomy. We conclude that when symptoms of respiratory distress and failure to thrive coexist in patients with PRS despite conservative management, surgical intervention to the airway is mandatory. TLA should be the first surgical procedure considered and if the ultimate goals of weight gain and respiratory comfort are still not achieved then tracheostomy seems inevitable. PMID- 2110819 TI - Probing the bacteriochlorophyll binding site by reconstitution of the light harvesting complex of Rhodospirillum rubrum with bacteriochlorophyll a analogues. AB - Structural features of bacteriochlorophyll (BChl) a that are required for binding to the light-harvesting proteins of Rhodospirillum rubrum were determined by testing for reconstitution of the B873 or B820 (structural subunit of B873) light harvesting complexes with BChl a analogues. The results indicate that the binding site is very specific; of the analogues tested, only derivatives of BChl a with ethyl, phytyl, and geranylgeranyl esterifying alcohols and BChl b (phytyl) successfully reconstituted to form B820- and B873-type complexes. BChl analogues lacking magnesium, the C-3 acetyl group, or the C-13(2) carbomethoxy group did not reconstitute to form B820 or B873. Also unreactive were 13(2)-hydroxyBChl a and 3-acetylchlorophyll a. Competition experiments showed that several of these nonreconstituting analogues significantly slowed BChl a binding to form B820 and blocked BChl a-B873 formation, indicating that the analogues may competitively bind to the protein even though they do not form red-shifted complexes. With the R. rubrum polypeptides, BChl b formed complexes that were further red-shifted than those of BChl a; however, the energies of the red shifts, binding behavior, and circular dichroism (CD) spectra were similar. B873 complexes reconstituted with the geranylgeranyl BChl a derivative, which contains the native esterifying alcohol for R. rubrum, showed in-vivo-like CD features, but the phytyl and ethyl B873 complexes showed inverted CD features in the near infrared. The B820 complex with the ethyl derivative was about 30-fold less stable than the two longer esterifying alcohol derivatives, but all formed stable B873 complexes. PMID- 2110820 TI - Duplex oligodeoxyribonucleotides cross-linked by mitomycin C at a single site: synthesis, properties, and cross-link reversibility. AB - Oligodeoxyribonucleotides cross-linked by reductively activated mitomycin C (MC) were prepared and purified for the first time. The cross-linked products were structurally characterized by nucleoside and MC-nucleoside adduct analysis. Optimal conditions were established for the cross-linking reaction, resulting in high yields, typically in the 20-50% range. Nuclease digests of the cross-linked oligonucleotides yielded the same bifunctional MC-deoxyguanosine adduct as that previously isolated from DNA exposed to MC in vitro and in vivo [Tomasz et al. (1987) Science 235, 1204]. The cross-linked oligonucleotides displayed broad thermal melting profiles, greatly increased Tm, and complex circular dichroism spectra. Phosphodiester linkages at the cross-link were resistant to spleen exonuclease, nuclease P1, and TaqI and ClaI restriction endonucleases; snake venom diesterase action was uninhibited. The cross-links are stable to heat at neutral pH but are removed by treatment in hot piperidine or by the reducing agents Na2S2O4 and dithiothreitol. Mechanisms are proposed for these reactions. These studies define optimal methods for introducing mitomycin cross-links into DNA fragments at a specific site, providing a versatile tool to study the effects of the MC cross-links on DNA structure and function. PMID- 2110821 TI - Recognition between mitomycin C and specific DNA sequences for cross-link formation. AB - An extensive series of oligodeoxyribonucleotides was reacted with reductively activated mitomycin C (MC), and the resulting cross-linked drug-oligonucleotide complexes were isolated by reverse-phase HPLC and characterized by nucleoside and MC-nucleoside adduct analysis. HPLC also served for assay of the yield of cross linked oligonucleotides. AT-rich duplex oligonucleotides, containing a single central CG.CG, gave high yields of cross-links between the two guanines while those having GC.GC, instead, gave none. In another series, the central sequences CGC.GCG and CGC.ICG both yielded 50% cross-link while CGC.GCI was completely resistant. Cross-linking was conducted also in two steps: Oligonucleotides substituted monofunctionally by MC at guanine at either a CG or GC sequence were annealed with their complementary strands followed by reductive reactivation of the bound MC to form a cross-link. The CG oligomers were cross-linked quantitatively while the GC ones were again resistant. These results show unambiguously that the MC cross-link is absolutely specific to the CG.CG duplex sequence, confirming our previous finding [Chawla, A.K., Lipman, R., & Tomasz, M. (1987) in Structure and Expression, Volume 2: DNA and Its Drug Complexes (Sarma, R.H., & Sarma, M.H., Eds.) Adenine Press, Guilderland, NY]. Evidence is presented that this specificity is due to the specific orientation of the monofunctionally attached MC in the minor groove. Superimposed on the CG.CG requirement, a four base-pair sequence preference was observed at PuCGPyr.PuCGPyr sequences. This suggests that the guanine N2 atom of GpPyr is more reactive toward the drug than that of GpPu, due to the favorable effect of the negative dipole of the O2 of the Pyr on the reaction; in accordance, GpT was more reactive than GpC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110822 TI - Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver. AB - Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1--- 4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1--- 4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1--- 4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1--- 4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity. PMID- 2110823 TI - Folding of ribonuclease T1. 1. Existence of multiple unfolded states created by proline isomerization. AB - It is our aim to elucidate molecular aspects of the mechanism of protein folding. We use ribonuclease T1 as a model protein, because it is a small single-domain protein with a well-defined secondary and tertiary structure, which is stable in the presence and absence of disulfide bonds. Also, an efficient mutagenesis system is available to produce protein molecules with defined sequence variations. Here we present a preliminary characterization of the folding kinetics of ribonuclease T1. Its unfolding and refolding reactions are reversible, which is shown by the quantitative recovery of the catalytic activity after an unfolding/refolding cycle. Refolding is a complex process, where native protein is formed on three distinguishable pathways. There are 3.5% fast-folding molecules, which refold within the millisecond time range, and 96.5% slow-folding species, which regain the native state in the time range of minutes to hours. These slow-folding molecules give rise to two major, parallel refolding reactions. The mixture of fast- and slow-folding molecules is produced slowly after unfolding by chain equilibration reactions that show properties of proline isomerization. We conclude that part of the kinetic complexity of RNase T1 folding can be explained on the basis of the proline model for protein folding. This is supported by the finding that the slow refolding reactions of this protein are accelerated in the presence of the enzyme prolyl isomerase. However, several properties of ribonuclease T1 refolding, such as the dependence of the relative amplitudes on the probes, used to follow folding, are not readily explained by a simple proline model. PMID- 2110824 TI - Folding of ribonuclease T1. 2. Kinetic models for the folding and unfolding reactions. AB - The slow refolding of ribonuclease T1 was investigated by different probes. Structural intermediates with secondary structure are formed early during refolding, as indicated by the rapid regain of a native-like circular dichroism spectrum in the amide region. This extensive structure formation is much faster than the slow steps of refolding, which are limited in rate by the reisomerization of incorrect proline isomers. The transient folding intermediates were also detected by unfolding assays, which make use of the reduced stability of folding intermediates relative to that of the native protein. The results of this and the preceding paper [Kiefhaber et al. (1990) Biochemistry (preceding paper in this issue)] were used to propose kinetic models for the unfolding and refolding of ribonuclease T1. The unfolding mechanism is based on the assumption that, after the structural unfolding step, the slow isomerizations of two X-Pro peptide bonds occur independently of each other in the denatured protein. At equilibrium a small amount of fast-folding species coexists with three slow folding species: two with one incorrect proline isomer each and another, dominant species with both these prolines in the incorrect isomeric state. In the mechanism for refolding we assume that all slow-folding molecules can rapidly regain most of the secondary and part of the tertiary structure early in folding. Reisomerizations of incorrect proline peptide bonds constitute the slow, rate limiting steps of refolding. A peculiar feature of the kinetic model for refolding is that the major unfolded species with two incorrect proline isomers can enter two alternative folding pathways, depending on which of the two reisomerizes first. The relative rates of reisomerization of the respective proline peptide bonds at the stage of the rapidly formed intermediate determine the choice of pathway. It is changed in the presence of prolyl isomerase, because this enzyme catalyzes these two isomerizations with different efficiency and consequently leads to a shift from the very slow to the intermediate refolding pathway. PMID- 2110825 TI - Characterization of the RAD10 gene of Saccharomyces cerevisiae and purification of Rad10 protein. AB - The RAD10 gene of Saccharomyces cerevisiae is one of at least five genes required for damage-specific incision of DNA during nucleotide excision repair. This gene was previously cloned and sequenced [Weiss, W. A., & Friedberg, E. C. (1985) EMBO J. 4, 1575-1582; Reynolds et al. (1985) EMBO J. 4, 3549-3552]. In the present studies, we have mapped one major and three minor transcriptional start sites in the RAD10 gene. The locations of these sites relative to the translational start codon are remarkably similar to those previously identified in the yeast RAD2 gene [Nicolet et al. (1985) Gene 36, 225-234]. The two genes also share common sequences in these regions. However, in contrast to RAD2 [Robinson et al. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 1842-1846], RAD10 is not induced following exposure of cells to the DNA-damaging agent 4-nitroquinoline 1-oxide. Native RAD10 protein and also two different Rad10 fusion proteins are rapidly degraded in most Escherichia coli strains. However, following overexpression of the cloned RAD10 gene in yeast, native Rad10 protein was purified to greater than 90% homogeneity. A catalytic function has not been identified for the purified protein. RAD10 cells (untransformed with the cloned gene) contain fewer than 500 molecules per cell. This is similar to the levels of the UvrA, UvrB, and UvrC nucleotide excision repair proteins in E. coli. PMID- 2110826 TI - Trifluoperazine binding to porcine brain calmodulin and skeletal muscle troponin C. AB - Binding of trifluoperazine (TFP), a phenothiazine tranquilizer, to porcine brain calmodulin (CaM) and rabbit skeletal muscle troponin C (Tn C) was measured by an automated high-performance liquid chromatography binding assay using a molecular sieving column; 10 micrograms of either protein per injection is sufficient for determining TFP binding, and results are comparable to those obtained by equilibrium dialysis. Very little binding was observed to either protein in the absence of Ca2+ while in the presence of Ca2+ both proteins bind 4 equiv of TFP. Other characteristics of TFP binding however are different for each protein. For CaM, half-maximal binding occurs at 5.8 microM TFP, the Hill coefficient is 0.82, and the fit of the data to the Scatchard equation is consistent with four independent TFP-binding sites. Binding of one melittin displaces two TFP from CaM. Thus, there are two recognizable classes of TFP-binding sites: those that are displaced by melittin and those that are not. TFP causes an increase in the Ca2+ affinity of CaM, and three Ca2+ must be bound to CaM for TFP binding to occur. The studies also yielded a measure of the intrinsic affinity of three of CaM's Ca2(+)-binding sites that is in agreement with previous reports. For troponin C, half-maximal binding occurs at 16 microM TFP, the Hill coefficient is 1.7, and the data best fit the Adair equation for four binding sites. The measured constants K1, K2, K3, and K4 were 2.5 X 10(4), 6.6 X 10(3), 5.8 X 10(5), and 2.0 X 10(5) M-1, respectively, in 1 mM Ca2+ and were similar when Mg2+ was additionally included. TFP also increases troponin C's Ca2+ affinity, and it is the low-affinity, Ca2(+)-specific binding sites that are affected. These studies yielded a measure of the intrinsic affinity of these Ca2(+)-binding sites that is in agreement with previous measurements. PMID- 2110827 TI - Association to HeLa cells and surface behavior of exogenous gangliosides studied with a fluorescent derivative of GM1. AB - Cultured HeLa cells were incubated with pyrene-GM1/3H-radiolabeled GM1 ganglioside (1:4 M/M) mixtures for various times. The process of association of pyrene-GM1 with cells was qualitatively and quantitatively the same as that of 3H GM1. The pyrene-GM1 and 3H-GM1 proportions in the various forms of association with cells were similar to that of the starting ganglioside mixture. After 2-h incubation, the association of ganglioside with cells was well established whereas almost no metabolic processing had occurred. During a 24-h incubation, pyrene- and 3H-GM1 underwent similar metabolic processing and gave rise to catabolic (GM2 and GM3) and anabolic (GD1a) derivatives. Fluorescence spectroscopy experiments carried out with the excimer formation technique on subcellular fractions containing plasma membranes showed that exogenous ganglioside was, in part, associated with the cells in a micellar form removable by trypsin treatment, and in part inserted in a seemingly molecular dispersion. Addition of Ca2+ salts caused aggregation of the ganglioside, as indicated by the increase of the excimer:monomer fluorescence ratio. The phenomenon was Ca2+ concentration dependent (maximum at 10 mM), and subsequent addition of EDTA had no effect. The saccharide portion of exogenously incorporated pyrene-GM1 was available to interact with external ligands, as shown by its ability to bind cholera toxin whose addition reduced the collision rate among the ganglioside lipid moieties. PMID- 2110828 TI - Shift of binding site at the interface between actin and myosin. AB - The molar ratio dependent change in the binding manner between actin and the lysine-rich sequence at the junction between 50K and 20K domains of subfragment 1 was studied by both protease digestion and cross-linking with 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide. The tryptic cleavage site at the function between 50K and 20K was found to be located between the third and fourth lysine residues in the lysine-rich sequence -KKGGKKK-. This site was not protected by actin when the molar ratio of actin to subfragment 1 was 1:1 but was protected at 2:1 and 3:1. The V8 protease cleavage site of chicken subfragment 1 and the elastase cleavage site of rabbit subfragment 1 were found to be located four residues away from the N-terminus of the lysine-rich sequence. Unlike the tryptic cleavage site, this site was protected by actin more when the molar ratio of actin to subfragment 1 was 1:1 than when it was 2:1 and 3:1. To understand the reason for the opposite effect of the molar ratio observed at the middle of and at four residues away from the lysine-rich sequence, actual cross-linked residue(s) was (were) determined by subjecting cross-linked product to a protein sequencer. It was found that the cross-linked sites were mainly at the first and second lysine residues of the lysine-rich sequence when the molar ratio of actin to subfragment 1 was 1:1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110829 TI - Identification of localized redox states in plant-type two-iron ferredoxins using the nuclear Overhauser effect. AB - The homonuclear Overhauser effect (NOE), in conjunction with nonselective spin lattice relaxation measurements, has been employed to assign the contact-shifted resonances for the reduced form of two typical plant-type two-iron ferredoxins from the algae Spirulina platensis and Porphyra umbilicalis. These results demonstrate that the NOE should have broad general applicability for the assignments and electronic structural elucidation of diverse subclasses of paramagnetic iron-sulfur cluster proteins. NOE connectivities were detected only among sets of resonance exhibiting characteristically different deviations from Curie behavior, providing strong support for the applicability of the spin Hamiltonian formulation for the NMR properties of the antiferromagnetically coupled iron clusters [Dunham, W. R., Palmer, G., Sands, R. H., & Bearden, A. J. (1971) Biochim. Biophys. Acta 253, 373-384; Banci, L., Bertini, I., & Luchinat, C. (1989) Struct. Bonding (in press)]. The geminal beta-methylene protons for the two cysteines bound to the iron(II) center were clearly identified, as well as the C alpha H and one C beta H for each of the cysteines bound to the iron(III). The identification of the iron bound to cysteines 41 and 46 as the iron(II) in the reduced protein was effected on the basis of dipolar contacts between the bound cysteines, as predicted by crystal coordinates of S. platensis Fd [Tsukihara, T., Fukuyama, K., Nakamura, M., Katsube, Y., Tanaka, N., Kakudo, M., Wada, K., Hase, T., & Matsubara, H. (1981) J. Biochem. (Tokyo) 90, 1763 1773].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110830 TI - Satellite DNAs contain sequences that induced curvature. AB - The repeating units of mouse, rat, and alpha-monkey satellites have been cloned. All three show properties that are characteristic of curved DNA: (i) their migration in polyacrylamide gels is slower than predicted from their sequences, and (ii) they appear as curved molecules when visualized by electron microscopy. All three satellite repeats contain runs of d(A.T)n greater than or equal to 3 residues that are likely to be responsible for their curvature. From analysis of 20 different satellite DNA sequences, we conclude that, in satellite DNA, adenine residues show a high tendency to cluster in groups of three or more. PMID- 2110831 TI - Expression of UDP-glucuronosyltransferase cDNA in Saccharomyces cerevisiae as a membrane-bound and as a cytosolic form. AB - The mouse clone UDPGTm-1 encodes a UDP-glucuronosyltransferase enzyme which was isolated from a lambda gt11 cDNA library constructed with phenobarbital-induced liver mRNA [Kimura, T., & Owens, I. S. (1987) Eur. J. Biochem. 168, 515-521]. In order to establish substrate specificity, UDPGTm-1 was inserted into the yeast vector pEVP11 and expressed in Saccharomyces cerevisiae strain AH22. Cells transformed with the expression unit pUDPGTm-1c (insert in correct orientation with respect to promoter) stably transcribe the transferase cDNA. Consistent with the presence of mRNA, pUDPGTm-1c-transformed AH22 cells synthesize a transferase protein with Mr congruent to 51,000 by Western immunoblot analysis. The membrane bound transferase expressed in yeast in glycosylated as indicated by its enhanced electrophoretic mobility in a SDS-polyacrylamide gel following endoglycosidase H treatment and detection by Western immunoblot analysis. A survey, using 12 aglycons in an assay with microsomes from cells which express the protein, shows preferential glucuronidation of naphthol and estrone followed by p-nitrophenol. Testosterone, phenolphthalein, dihydrotestosterone, androsterone, and 4 methylumbelliferone are conjugated at an intermediate level. There is barely detectable glucuronidation of 3-hydroxy- and 9-hydroxybenzo[a]pyrene and no detectable conversion of morphine or lithocholic acid. The truncated cDNA (lacking the putative membrane-insertion signal-peptide coding sequence, but with a newly adapted translation-start codon) is ligated into pAAH5 and is expressed as a cytosolic transferase form in the protease-deficient ZA521 strain of S. cerevisiae. The Mr congruent to 51,000-52,000 is similar to that seen in microsomes from AH22 cells where the protein is presumably processed as it is inserted into the membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110832 TI - Lanthanide(III)-phosphatidic acid complexes: binding site heterogeneity and phase separation. AB - The luminescent lanthanides are potentially useful probes of cation-induced events involving phospholipid membranes. In this work, the spectroscopic properties of Tb3+, Ce3+ and Eu3+ are shown to be complementary in defining three forms of complex with phosphatidic acid vesicles. Ce3+, in particular, is useful for studying dilute cation-lipid complexes because it has strong excitation bands in the near ultraviolet. In addition to providing a means for detecting chemically distinct forms of lanthanide-lipid complexes, the luminescence can be used to monitor cation-induced lateral segregation. Ce3+ to Tb3+ energy transfer was observed at lanthanide levels as low as 1:1000 Ln3+/phosphatidic acid, indicating clustering or phase separation. Initial clustering occurs on a subsecond timescale, followed by a much slower aggregation continuing for several minutes to hours. Addition of a chelator results in slow release of the lanthanides. In the case of the dioleoylphosphatidic acid complexes, release is bimodal and indicative of cation entrapment; dimyristoylphosphatidic acid complexes exhibit this behavior only at high temperatures. These observations are consistent with the relative tendencies of these two lipids to form the HII phase. This work sets the foundation for experiments designed to determine the size of nucleation sites for cation-induced events such as intramembrane inverted micelle formation and membrane fusion. PMID- 2110833 TI - Transfer of human membrane surface components by incorporating human cells into intact animal tissue by cell-tissue electrofusion in vivo. AB - Current animal models employed for the study of the obligate human pathogen Neisseria gonorrhoeae fail to utilize specific human gonococcal attachment receptors required to initiate pathogenesis in a clinically meaningful way. This communication presents evidence that suggests that cell-tissue electrofusion may be employed to create an animal model for this human specific pathogen. This new biotechnology was used to incorporate human membrane gonococcal receptors directly into epithelium of laboratory animals and subsequently infecting the histologically modified tissue with N. gonorrhoeae strain Pgh 3-2. PMID- 2110834 TI - The influence of calcium ionophore and activators of protein kinase C on steroid production by preovulatory ovarian follicles of the goldfish. AB - Steroidogenesis in teleost fish, as in other vertebrate groups, is mediated by the activation of adenylate cyclase. For the present studies, calcium ionophore A23187 and either phorbol 12-myristate 13-acetate (PMA) or 1-oleoyl-2 acetylglycerol (OAG) were used to investigate the possible roles that changes in intracellular calcium content and protein kinase C activation play in steroid production by goldfish preovulatory ovarian follicles incubated in vitro. While ineffective alone, PMA (1.6-400 nM) and OAG (25-100 micrograms/ml) exhibited classical synergism with A23187 (1.0-10 microM), leading to increased testosterone production. The magnitude of these responses was at least tenfold lower than that obtained with human chorionic gonadotropin (hCG), forskolin, or dibutyryl cyclic adenosine 3',5'-monophosphate. Testosterone production stimulated by hCG and forskolin was blocked by addition of PMA but not OAG. Unlike PMA, the inactive phorbol ester 4 alpha-phorbol 12,13-dideconate did not influence basal or stimulated testosterone production. A23187 had a biphasic effect on stimulated testosterone production: a dosage of 0.25 or 1.0 microM potentiated the action of submaximally effective dosages of hCG or forskolin on testosterone production; a higher dosage of 4 microM inhibited stimulated testosterone production by up to 50%. In conclusion, these studies suggest that, in addition to the adenylate cyclase second messenger system, changes in intracellular calcium and activation of protein kinase C may modulate steroidogenesis in goldfish ovarian follicles. PMID- 2110835 TI - Changes in follicular populations, in serum estrogen and progesterone, and in ovarian steroid secretion in vitro during the guinea pig estrous cycle. AB - It has been proposed that the guinea pig estrous cycle manifests biphasic follicular development. The follicles of one cohort apparently achieve their greatest diameter by approximately Day 10 of the cycle and then undergo atresia while the second cohort ovulates; this constitutes an uninvestigated and novel model for the evaluation of atresia. In this study, follicular development was evaluated in vivo and in vitro to confirm this pattern. On cycle Day 3, 5, 7, 10, 12, 15 or 0 (ovulation), guinea pigs were killed and trunk blood was collected; ovaries were excised, weighed, and measured, and size and number of large (greater than 400 microns) follicles were determined. Ovaries were quartered and placed into culture dishes for incubation. Culture variables were presence or absence of human follicle-stimulating hormone (100 ng/ml) and time. Ovarian fragments were processed for histology. Estrogen (E) and progesterone (P) in sera and culture media were analyzed by radioimmunoassay. The abundance of large follicles on both the ovarian surface (greater than 635 microns) and in histologic section (greater than 500 microns) relative to all follicles observed was high on Day 7 and Day 10, respectively; lower on Day 10 and Day 12; and high again at Day 12 and Day 15. Mean secretion of E in culture was elevated on Day 10 (253.0 +/- 60.3 pg/ml/mg ovary), low on Day 12 (67.9 +/- 13.0), and high again on Day 0 (185.8 +/- 56.8). Peripheral P reached a maximum of 2.93 +/- 0.09 ng/ml (Day 5), and then declined to Day 15.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110836 TI - Gonadotropin secretion in ovariectomized ewes: effect of passive immunization against gonadotropin-releasing hormone (GnRH) and infusion of a GnRH agonist and estradiol. AB - Gonadotropin secretion was examined in ovariectomized sheep after passive immunization against gonadotropin-releasing hormone (GnRH). Infusion of ovine anti-GnRH serum, but not control antiserum, rapidly depressed serum concentrations of luteinizing hormone (LH). The anti-GnRH-induced reduction in serum LH was reversed by circhoral (hourly) administration of a GnRH agonist that did not cross-react with the anti-GnRH serum. In contrast, passive immunization against GnRH led to only a modest reduction in serum concentrations of follicle stimulating hormone (FSH). Pulsatile delivery of the GnRH agonist did not influence serum concentrations of FSH. Continuous infusion of estradiol inhibited and then stimulated gonadotropin secretion in animals passively immunized against GnRH, with gonadotrope function driven by GnRH agonist. However, the magnitude of the positive feedback response was only 10% of the response noted in controls. These data indicate that the estradiol-induced surge of LH secretion in ovariectomized sheep is the product of estrogenic action at both hypothalamic and pituitary loci. Replacement of the endogenous GnRH pulse generator with an exogenous generator of GnRH-like pulses that were invariant in frequency and amplitude could not fully reestablish the preovulatory-like surge of LH induced by estradiol. PMID- 2110837 TI - Increased germ cell degeneration during postprophase of meiosis is related to increased serum follicle-stimulating hormone concentrations and reduced daily sperm production in aged men. AB - Aged men, known to have high serum gonadotropin levels and reduced spermatogenic potential, were used to study the relationship between serum follicle-stimulating hormone (FSH) and germ cell degeneration. Serum hormones were measured from blood obtained at autopsy. Phase-contrast cytometry was used to enumerate germ cells in homogenates of fixed testes from 13 younger (24-51 yr) and 14 aged (69-90 yr) men. The developmental steps of spermatogenesis during which germ cells degenerate were determined by comparing potential daily sperm production based on primary spermatocytes with daily sperm production based on two different types of spermatids. During spermiogenesis, there was no significant degeneration in the younger or aged men. During postprophase of meiosis, aged men had more (p less than 0.01) germ cell degeneration, significantly lower (p less than 0.05) serum testosterone, and greater (p less than 0.01) serum FSH than did younger men. Germ cell degeneration during postprophase of meiosis was negatively correlated (p less than 0.01) to daily sperm production and significantly (p less than 0.01) related to serum concentrations of FSH. As revealed in these aged men, meiotic germ cell degeneration has a direct effect on daily sperm production and is significantly related to serum FSH concentrations. PMID- 2110838 TI - Ovarian prostaglandin endoperoxide synthase: cellular localization during the rat estrous cycle. AB - The specific cellular localization of prostaglandin endoperoxide (PGH) synthase was studied throughout the rat estrous cycle. Animals were necropsied at 1300 h on each day of the 4-day cycle, and an additional group was necropsied at 2300 h on proestrus. Ovaries were removed and processed for cellular identification of PGH synthase by immunohistochemistry. At all stages of the cycle, intense immunostaining was observed in newly formed corpora lutea. Luteal cells were immunoreactive, but the connective tissue centrum was unstained. Interstitial tissue contained heavily labeled cells, whereas the germinal epithelium exhibited faint staining. During estrus, metestrus, and diestrus, thecal cells from preantral and antral follicles contained PGH synthase immunoreactivity, but granulosa cells were unstained. Faint staining of mural granulosa cells was observed first in 78% of preovulatory follicles (less than 400-microns diameter) in ovaries collected on the afternoon of proestrus. After the luteinizing hormone surge, 95% of the preovulatory follicles exhibited PGH synthase staining. The percentage of immunoreactive granulosa cells in these preovulatory follicles increased 4-fold in ovaries collected at 2300 h on proestrus. The presence of ovarian PGH synthase throughout the rat estrous cycle and the changes in cellular localization may reflect the potential role of PGs in follicular and luteal function. PMID- 2110839 TI - Diisopropyl fluorophosphate labeling of sperm-associated proteinases. AB - Proteinase inhibitors have been shown to be capable of preventing various aspects of fertilization. Diisopropyl fluorophosphate (DFP) is an irreversible inhibitor of trypsin-like enzymes that is commercially available in a radiolabeled form. The experiments described herein were designed to determine if DFP would prevent sperm function in live, motile sperm and to identify the sperm proteins bound with DFP. DFP at 5 mM concentrations had no observable effect on sperm motility, but inhibited the penetration of zona-free hamster ova by human sperm (5.5%) compared to controls (33.5%). Acid extracts of motile sperm that had been incubated with radiolabeled DFP and collected by the swim-up procedure demonstrated the presence of radiolabeled DFP, and the autoradiography of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels of these extracts localized the uptake of radiolabeled DFP to proteins in the molecular weight region of the proacrosin-acrosin system. Acid-extracted proteinases from semen samples incubated with DFP demonstrated a concentration dependent inhibition of both esterolytic hydrolysis of benzoyl-arginine ethyl ester on spectrophotometric analysis and proteolytic activity on gelatin SDS-PAGE zymography. DFP-labeled proteins were precipitated by highly specific antibodies to proacrosin. These results demonstrated that DFP is capable of inhibiting sperm function, and that it associates with the proacrosin-acrosin system in live motile sperm. PMID- 2110840 TI - Synthetic factor VIII peptides with amino acid sequences contained within the C2 domain of factor VIII inhibit factor VIII binding to phosphatidylserine. AB - The effective activation of factor X by factor IXa requires the co-factor activity of activated factor VIII (FVIII). Factor Xa formation is also dependent on the presence of negatively charged phospholipid. A phospholipid binding domain of FVIII has been reported to be present on the FVIII light chain. Recent observations on a subset of human FVIII inhibitors have implicated the carboxyl terminal C2 domain of FVIII as containing a possible phospholipid binding site. The purpose of this study was to investigate directly the role of the C2 domain in phospholipid binding. Twenty-six overlapping peptides, which span the entire C2 domain of FVIII, were synthesized. The ability of these peptides to inhibit the binding of purified human FVIII to immobilized phosphatidylserine was evaluated in an enzyme-linked immunosorbent assay. Three overlapping synthetic FVIII peptides, 2303-2317, 2305-2332, and 2308-2322, inhibited FVIII binding to phosphatidylserine by greater than 90% when tested at a concentration of 100 mumols/L. A fourth partially overlapping peptide, 2318-2332, inhibited FVIII binding by 65%. These results suggest that the area described by these peptides, residues 2303 to 2332, may play an important role in the mediation of FVIII binding to phospholipid. PMID- 2110841 TI - Mass screening: theory and ethics. PMID- 2110842 TI - Effect of parenteral oestrogen on the coagulation system in patients with prostatic carcinoma. AB - Patients with prostatic carcinoma on oral oestrogen therapy have an altered coagulation system and suffer cardiovascular side effects. Oestrogens--especially oral oestrogens--are potent inducers of liver synthesised proteins, including coagulation factors. We have assessed the effect of non-oral oestrogen on the coagulation system in patients with prostatic carcinoma. Twelve patients were given monthly intramuscular injections of 320 mg polyoestradiol phosphate (PEP). No additional oestrogens were given. No change was found in any of the coagulation factors, including factor VII, with the exception of a significant decrease in antithrombin III. No patient, including 38 patients treated with PEP, had any cardiovascular complications after a mean follow-up period of 12.9 +/- 0.7 months; 76% of the patients responded to treatment. Parenteral administration of oestrogen caused a less marked change in the coagulation system than oral administration and should be the treatment of choice for prostatic carcinoma. PMID- 2110843 TI - Reduction of arginine vasopressin binding sites in mouse lateral septum by treatment with 6-hydroxydopamine. AB - The neuropeptide arginine vasopressin modulates neuroadaptive processes, including memory consolidation and functional tolerance to ethanol, by actions at CNS V1 receptors. Noradrenergic systems play a role in these actions of the peptide. To assess whether vasopressin may act presynaptically on catecholamine neurons, vasopressin receptors were measured by quantitative autoradiography in the lateral septum, an area that is innervated by catecholaminergic neurons and has a high density of V1 receptors, of control and 6-hydroxydopamine-treated mice. Vasopressin receptors were distributed non-uniformly throughout the lateral septum, with greater binding in the more caudal regions. Treatment with 6 hydroxydopamine lowered septal catecholamine levels and vasopressin binding, with a greater effect on binding in the intermediate and caudal portions of the lateral septum. Pretreatment with desmethylimipramine reversed the depletion of norepinephrine, and attenuated the effect of 6-hydroxydopamine on vasopressin binding in the intermediate region, but was less effective in the caudal region of the lateral septum. The results suggest that a portion of septal vasopressin receptors are localized on the terminals of noradrenergic and, possibly, dopaminergic neurons, consistent with the hypothesis that certain neuroadaptive responses to vasopressin could be mediated by modulation of neurotransmitter release. In contrast to the results with 6-hydroxydopamine, treatment of mice with 5,7-dihydroxytryptamine, to destroy serotonergic terminals, did not alter vasopressin binding in the lateral septum. PMID- 2110844 TI - Effects of long-term theophylline treatment on adenosine A1-receptors in rat brain: autoradiographic evidence for increased receptor number and altered coupling to G-proteins. AB - The effects of 2 weeks' treatment with theophylline (20 mg/kg i.p.) on the binding to adenosine A1-receptors was studied by autoradiography using the agonist [3H]N6-cyclohexyladenosine ([3H]CHA) and the antagonist [3H]8-cyclopentyl 1,3-dipropylxanthine ([3H]DPCPX) as ligands. A significant increase (10%) in [3H]CHA binding was measured only in the frontoparietal cortex. However, if the brain sections were incubated in the presence of 5 microM guanosine-5' triphosphate (GTP), which by itself decreased binding by between 15 and 80% depending on the region, the increase in the frontoparietal cortex was larger (30%) and significant increases of the same magnitude were also seen in several other structures, e.g. the caudate putamen and the central gray matter of the midbrain. In some regions, for example the hippocampus and the cerebellar cortex, small or no increases were seen. GTP 100 microM practically eliminated [3H]CHA binding in both control and treated animals, suggesting that these receptors are all coupled to G-proteins. The binding of [3H]DPCPX was increased significantly only in the frontoparietal and striate cortex (5-10%). These results suggest that the theophylline treatment had little on the total receptor number but may have altered the coupling between A1-receptors and regulatory GTP-binding proteins. PMID- 2110845 TI - Restoration of cholinomimetic activity by clonidine in cholinergic plus noradrenergic lesioned rats. AB - The effects of combined lesions of forebrain cholinergic and noradrenergic systems on memory and responsivity to the memory enhancing effects of cholinomimetics were investigated in rats. Forebrain noradrenergic deficits produced by the injection of 6-hydroxydopamine into the ascending noradrenergic bundle (ANB) blocked the ability of cholinomimetics such as physostigmine and oxotremorine to enhance retention test performance in nucleus basalis of Meynert lesioned rats. Low doses of the noradrenergic receptor agonist clonidine, when administered in conjunction with cholinomimetics reversed this blockade. These results suggest that combined cholinergic/noradrenergic therapy may be of value in the treatment of some Alzheimer's disease patients. PMID- 2110846 TI - Effects of divalent cations on the frequency of spontaneous action potentials from the lateral line organ of Xenopus laevis. AB - The effect of superfusion of the internal surface of the skin of Xenopus laevis with saline containing Co2+, Ca2+, Mg2+, or Ba2+, on the frequency of spontaneous action potentials of the lateral line nerve, was studied to investigate the role of extracellular Ca2+ in spontaneous neural activity. Addition of divalent cations to frog saline, either singly or as a mixture of two different ions, produced concentration-dependent suppression of spontaneous rate. The rank order of potency for suppression by each ion, perfused alone, was Co2+ greater than Ca2+ greater than Mg2+ greater than Ba2+. Suppression by combinations of Mg2+ and Co2+, or of Ca2+ and Co2+, was approximated by the sum of the suppressive effects of each cation. Ca2+ was more suppressive than Mg2+ when each of these ions was paired with the same amount of Co2+, while Ca2+ was approximately as suppressive as Co2+ when similarly paired with Mg2+. One interpretation of the suppression by Ca2+ invokes the hypothesis that divalent cations suppress spontaneous activity by charge screening of voltage-sensitive Na+ channels on afferent dendrites and that release of neurotransmitter by the influx of extracellular Ca2+ through voltage-sensitive Ca2+ channels of hair cells may not be the sole mechanism for generation of spontaneous activity in the lateral line. These results quantify the relative suppressive potency of common divalent cations in the lateral line, and serve as a caveat to investigators who interpret a blockade of action potentials by high concentrations of Co2+ or Mg2+ as sufficient evidence for dependence of neurotransmission upon extracellular Ca2+, particularly in acousticolateralis systems. PMID- 2110847 TI - Amyloid beta-protein precursor accumulates in dystrophic neurites of senile plaques in Alzheimer-type dementia. AB - We raised two rabbit antisera against synthetic peptides corresponding to the carboxyl- and amino-terminal regions of the predicted amyloid beta-protein precursor (APP). Both antisera recognized the same 106-135 kDa proteins of human brain extract by immunoblot analysis. Immunocytochemical studies showed that these antisera both reacted with the same dystrophic neurites within the senile plaques of Alzheimer brains. These results indicated that APP accumulated in the dystrophic neurites of the senile plaques. PMID- 2110848 TI - Behavioral and biochemical effects of intra-accumbens dopaminergic grafts. AB - 6-Hydroxydopamine (6-OHDA) lesions in the ventral tegmental area (VTA) in rats prevented the hyperactivity response to methamphetamine in an open field. Transplantation of mesencephalic dopaminergic cells, obtained from rat embryos, into the nucleus accumbens (NAC) of 6-OHDA-lesioned animals restored the hyperactivity 4 weeks after grafting. By microdialysis of the NAC in freely moving rats no significant differences in baseline concentration of dopamine (DA) among the 3 groups (control, lesioned, grafted) were observed. However, after methamphetamine administration, DA increased significantly during the first 80 min in control animals, during the first 40 min in grafted animals, but did not increase in lesioned animals. On the other hand baseline concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased to one sixth to one third of those of controls in 6-OHDA-lesioned animals, and they did not respond to methamphetamine. After grafting, however, DOPAC and HVA restored to control levels and responded to methamphetamine with decreases as was observed in control animals. Data suggest that grafts not only restore the ability to release DA but also improve DA metabolism in the NAC. This might be a reason for recovery of locomotor activity. PMID- 2110849 TI - A "Gompertzian" view of osteoporosis. PMID- 2110850 TI - Fluoride treatment for osteoporosis. PMID- 2110851 TI - Epidemiology of osteoporosis: a study of fracture mortality in Italy. PMID- 2110852 TI - Absorbability of calcium sources: the limited role of solubility. AB - Fractional absorption of seven chemically defined calcium sources was measured in normal adult women under standardized load conditions. Solubility of the sources in water at neutral pH ranged from a low of 0.04 mM to a high of 1500 mM. The relationship of solubility to absorbability was weak. In the range from 0.1 to 10 mM, within which most calcium supplement sources fall, there was no detectable effect of solubility on absorption. Data from four food sources are presented for comparison. Absorbability of food calcium was not clearly related to absorbability of the dominant chemical form in the food concerned. These findings suggests that (1) even under controlled, chemically defined conditions, solubility of a source has very little influence on its absorbability; and (2) absorbability of calcium from food sources is determined mainly by other food components. PMID- 2110853 TI - Malabsorption of calcium in corticosteroid-induced osteoporosis. AB - We have examined the relation between radiocalcium absorption and serum 1,25 dihydroxyvitamin D [1,25(OH)2D3] levels in a set of 60 postmenopausal women on corticosteroid therapy (29 with and 31 without vertebral compression fractures) and compared these results with those from 31 normal postmenopausal women age matched with the "normal" corticosteroid-treated women. Radiocalcium absorption was a function of serum 1,25(OH)2D3 in both corticosteroid-treated groups and in the set as a whole, but the impaired calcium absorption in the corticosteroid treated patients with osteoporosis was not accounted for by their slightly reduced serum 1,25(OH)2D3 levels. This apparent resistance to the intestinal action of 1,25(OH)2D3 was quantified by a Z score which expresses, in standard deviation units, the difference between the measured calcium absorption and that predicted from the 1,25(OH)2D3 level. The Z score was significantly reduced in the osteoporotic group. Vertebral mineral density (VMD) was measured by quantitative computed tomography in 43 of the corticosteroid-treated cases and in all the normal postmenopausal women; analysis by VMD yielded similar conclusions. PMID- 2110854 TI - Load-induced proteoglycan orientation in bone tissue in vivo and in vitro. AB - Previous studies of Alcian blue-induced birefringence in adult avian cortical bone showed that a short period of intermittent loading rapidly produces an increased level of orientation of proteoglycans within the bone tissue. In the absence of further loading, this persists for over 24 hours. We have proposed that this phenomenon could provide a means for "capturing" the effects of transient strains, and so provide a persistent, constantly updated strain-related influence on osteocyte populations related to the bones' averaged recent strain history, in effect, a "strain memory" in bone tissue. In our present study, we use the Alcian blue-induced birefringence technique to demonstrate that proteoglycan orientation also occurs after intermittent loading of both cortical and cancellous mammalian bone in vivo and in vitro. We also show that the change in birefringence is proportional to the magnitude of the applied strain, and that the reorientation occurs rapidly, reaching a maximal value after only 50 loading cycles. Examination of electron micrographs of bone tissue after staining with cupromeronic blue allows direct visualization and quantification of the change in proteoglycan orientation produced by loading. This shows that intermittent loading is associated with a realignment of the proteoglycan protein cores, bringing them some 5 degrees closer to the direction of collagen fibrils in the bone matrix. PMID- 2110855 TI - Effect of cortisone on cells at the bone-marrow interface. AB - A study of the association between the rate of proliferation of marrow fibroblast like stromal cells (in vitro) and the rate of endosteal bone mineralization (EsMR) (in vivo) was undertaken in an osteopenic rat model. We report that 200 g male rats treated with cortisone acetate (5 mg/day for 7 days) exhibit decreases in marrow fibroblast colony-forming units (FCFU) and tetracycline-based measurements of EsMR at the level of the femoral midshaft. In cortisone-treated rats recovering for 1-3 weeks, the FCFU census and EsMR normalized during the first posttreatment week, remained at control levels after 2-3 weeks, and exhibited a relapse in the third week which signified only partial recovery. These changes were unrelated to patterns of body weight gain. The data indicate that the FCFU census can serve to index endosteal osteoblast vigor. PMID- 2110856 TI - Inhibitory effect of fluoride on the secretion of insulin. AB - The oral administration of sodium fluoride (NaF) (40 mumol/100 body weight [bw]) to fasting rats produced an immediate fall in insulin levels and the consequent increase in glycemia. These phenomena were observed with plasma fluoride concentrations 5-15 microM. Glycemia and insulin returned to normal levels within 4-5 hours, together with the washing out of fluoride from plasma and soft tissues. The insulin secretion of isolated Langerhans islets, perifused with solutions containing 5, 10, or 20 microM fluoride, was found to be significantly inhibited as a function of fluoride levels, both with basal and stimulatory concentrations of glucose. One hour after the intake of 60 mg of NaF, fasting human volunteers showed increased fluoride (5-15 microM) together with a significant fall of plasma insulin levels. PMID- 2110857 TI - Antibodies to meningococcal H.8 (Lip) antigen fail to show bactericidal activity. AB - Purified H.8 (Lip) antigen was coupled to tresyl-activated Sepharose 4B and used in affinity columns to purify anti-Lip antibodies from convalescent patient sera and from immune rabbit sera. Affinity-purified anti-Lip antibodies isolated from two convalescent patient sera contained 1000 and 1280 ELISA units of antibody and included antibodies of IgG, IgA, and IgM isotypes. An anti-Lip mouse monoclonal ascites (2-1-CA2) had 28,400 ELISA units of antibody. Bactericidal assays were performed using three different case strains of Neisseria meningitidis group B, namely 44/76, 8532, and 8047. Neither preparation of purified human anti-Lip antibodies had detectable bactericidal activity against strains 44/76 and 8532, but one of the two had a titer of 1:4 against strain 8047. Anti-Lip antibodies that were purified from immune rabbit serum and contained 1600 ELISA units of anti-Lip antibodies also failed to show detectable bactericidal activity. The rabbits were immunized with purified Lip antigen and showed specific antibody levels of 2000-2200 units by ELISA, but even the unfractionated sera had little or no bactericidal activity against the test strains. The high titer mouse monoclonal ascites had no bactericidal activity against the test strains. The poor bactericidal activity associated with monoclonal and polyclonal antibodies to the Lip antigen suggest that in spite of other attractive properties it may not be useful as a meningococcal vaccine. PMID- 2110858 TI - Receptors for transferrin in pathogenic bacteria are specific for the host's protein. AB - Transferrin receptors detected by a solid-phase binding assay were shown to be specific for the host's transferrin in the representative bacterial pathogens Neisseria meningitidis (human), Pasteurella haemolytica (bovine), and Actinobacillus pleuropneumoniae (porcine). Consistent with the receptor specificity, iron-deficient bacteria were only capable of utilizing transferrin from the host as a source of iron for growth. PMID- 2110859 TI - Coronary thrombolysis--clinical guidelines and public policy: results of an Ontario practitioner survey. AB - The Ontario Medical Association (OMA) guidelines for intravenous thrombolysis in acute myocardial infarction were released in March 1988 and contributed to a government decision against special per-case funding to assist hospitals using tissue-type plasminogen activator (tPA). In October 1988, 1512 cardiologists, internists and physician-administrators who were OMA members were mailed a questionnaire seeking their views on the OMA guidelines and related issues. Of the 419 questionnaires (28%) that were returned, 392 contained usable responses. Among the respondents 268 (68%) had used thrombolytic drugs in the preceding 12 months; the mean number of cases was 10.6 (standard deviation 12.9). A strong or a mild preference for tPA over streptokinase was registered by 64% of the respondents; 28% had no preference. However, the self-reported ratio of actual streptokinase:tPA use was about 3:1, and 73% indicated that the government's funding policy had limited the availability of tPA in their hospital. The respondents were almost equally divided as to whether the policy should be changed. The guidelines were deemed helpful by 85% of the noncardiologists, as opposed to 52% of the cardiologists (p less than 0.005). OMA involvement in developing and circulating such guidelines was supported by 74% of the respondents and opposed by 18%; opposition was more likely to come from those who found the guidelines unhelpful (p less than 0.001). Support for involvement by the College of Physicians and Surgeons of Ontario was much weaker (supported by 32%, opposed by 62%). Overwhelming opposition to government involvement was evident. PMID- 2110860 TI - Phase II study of doxorubicin plus ifosfamide/mesna in patients with advanced breast cancer. AB - Four courses of ifosfamide with mesna given by intravenous infusions were combined with bolus doxorubicin in a phase II trial to treat patients with breast cancer. Ifosfamide can deplete intracellular glutathione levels and because doxorubicin resistance may be associated with elevated levels of intracellular glutathione these drugs were combined in an attempt to overcome clinical cytotoxic drug resistance. There were 31 women with poor prognosis advanced breast cancer in the study. Forty-five percent were younger than 40 years old, 68% had visceral dominant disease, 59% had more than two disease sites, and each of the five women tested had increased expression of primary tumor epidermal growth factor receptor. The objective response rate was 71% with manageable toxicity (95% confidence interval, 54% to 85%). The response rate in 22 patients not given prior chemotherapy was 72% and in 9 patients with cancers resistant to previous mitoxantrone monotherapy it was 67%. The high antitumor activity of this combination suggests further exploration of its use in breast cancer. PMID- 2110861 TI - Modulation by all-trans retinoic acid of glycoprotein glycosylation in murine melanoma cells: enhancement of fucosyl- and galactosyltransferase activities. AB - beta-All-trans retinoic acid (RA) treatment of murine S91-C2 melanoma cells decreases in vitro growth and modulates the glycosylation of specific cellular and cell-surface glycoproteins. The effect of RA treatment on [3H]fucose, [3H]galactose, and [3H]glucosamine incorporation was investigated by metabolic labeling followed by analysis of labeled cellular glycoproteins using polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS PAGE) and fluorography. RA treatment dramatically increased the incorporation of the labeled monosaccharides into one glycoprotein of Mr 160,000 (gp160), which has been previously implicated in the growth-inhibitory effect of RA on these cells. Following RA treatment, cell-surface sialic acid residues on gp160 were also more intensely labeled by NaIO4 oxidation and subsequent NaB[3H]4 reduction than were those on gp160 of untreated cells. The activities of fucosyl- and galactosyltransferase increased about 1.5 to 1.9 times after RA treatment. These results suggest that the increased activities of the two glycosyltransferases is responsible for the increased incorporation of fucose and galactose into gp160. PMID- 2110862 TI - Tumour reducing and anticarcinogenic activity of selected spices. AB - Tumour reducing activity of extracts of eight commonly used spices in India were studied in mice transplanted intraperitoneally with Ehrlich ascites tumour. Oral administration of extracts of black pepper, asafoetida, pippali and garlic could increase the percentage of life span in these mice by 64.7%, 52.9%, 47% and 41.1%, respectively. However intraperitoneal administration of spice extracts did not produce any significant reduction in tumour growth except for sesame (38.8%). Garlic extract and asafoetida extracts also inhibited two stage chemical carcinogenesis induced by 7,12 dimethyl benzanthracene and croton oil on mice skin with significant reduction in papiloma formation. These results indicate the potential use of spices as anti-cancer agents as well as anti-tumour promoters. PMID- 2110864 TI - The epithelium overlying rabbit bronchus-associated lymphoid tissue does not express the secretory component of immunoglobulin A. AB - The epithelium associated with lymphoid aggregates in the bronchial tract (BALT) was studied in rabbits by immunohistochemistry using monoclonal antibodies against the secretory component (SC) of IgA. The normal bronchus epithelium was intensely labelled. In contrast, epithelium overlying the central parts of the follicles was negative. This specialized epithelium cannot participate in the SC mediated transport of IgA, which might be a basis for the adherence and transport of microorganisms into the lymphoid tissue, thus initiating immune responses of the BALT. PMID- 2110863 TI - Comparison of T suppressor factors from tumour-bearing mice and mice immunized with a monoclonal anti-idiotypic antibody. AB - Certain dosage schedules of a monoclonal anti-idiotypic antibody (related to a murine bladder carcinoma) were found to induce suppressor factor production by syngeneic mice. This suppressor factor resembled the factor from tumour-bearing mice with respect to idiotype specificity, possession of molecular markers (reactive with anti-IJ and B16G antibodies) and production by Lyt2+IJ+ T cells in spleen cell cultures. The two factors differed with respect to Igh restriction in an in vitro assay (leucocyte adherence inhibition) and ability to suppress the induction of delayed-type hypersensitivity to tumour antigen. PMID- 2110865 TI - Tau protein: an update on structure and function. PMID- 2110866 TI - Syntheses and biological activities of renin inhibitors containing statine analogues. AB - Syntheses and biological activities of dipeptide renin inhibitors that contain statine analogues are described. The key steps of the synthetic approach to dipeptide renin inhibitors are the asymmetric synthesis of 2(R)-substituted-3 aminocarbonylpropionic acids and the diastereoselective syntheses of (3S,4S) statine analogues. These inhibitors (2,14-40) inhibited human renin in the 3-140 nM range. Inhibitor ES 6864 (2) was found to be a highly potent inhibitor of human renin (IC50: 4.6 x 10(-9) M) and showed high enzyme specificity. Oral administration of ES 6864 at 3 mg/kg to conscious, sodium-depleted marmosets inhibited plasma renin activity (PRA) more than 80% after 1 h. PMID- 2110867 TI - Effects of Ca2+, Zn2+ and Cd2+ on uridine diphosphate-glucuronyltransferase and beta-glucuronidase activities in rat liver microsomes. AB - The effect of various metals on uridine diphosphate (UDP)-glucuronyltransferase and beta-glucuronidase activities in rat liver microsomes was investigated. The presence of Mn2+, Cd2+, Zn2+, V5+, Ni2+, Co2+, Cu+ or Ca2+ (20 microM) in the enzyme reaction mixture did not cause a significant alteration of UDP glucuronyltransferase activity in hepatic microsomes. Of these metals, Zn2+ and Cd2+ (20 microM) caused a remarkable increase in hepatic microsomal beta glucuronidase activity. Appreciable effects of Zn2+ and Cd2+ on beta glucuronidase activity were seen at 5.0 microM, and the effects were saturated at 50 microM. Ca2+ (5.0-50 microM) and/or the Ca2(+)-binding protein regucalcin (2.0 microM) did not have an appreciable effect on UDP-glucuronyltransferase and beta glucuronidase activities in hepatic microsomes. Thus, Zn2+ and Cd2+ uniquely increased beta-glucuronidase activity. The Zn2(+)- and Cd2(+)-induced increase in beta-glucuronidase activity was completely reversed by the presence of an SH group-protecting reagent (dithiothreitol). The response of the microsomal enzyme to Zn2+ and Cd2+ (20 microM) was no longer seen after treatment with 0.2% Triton X-100 [polyoxyethylene(10)octylphenyl ether], indicating that the stimulation by these metals is dependent on membrane association. The present study suggests that, of various metals tested, Zn2+ and Cd2+ can uniquely increase hepatic microsomal beta-glucuronidase activity and that their effect is based on binding to membranous SH groups, beside the enzyme protein. PMID- 2110868 TI - Studies on the enzyme immunoassay of bio-active constituents contained in oriental medicinal drugs. V. Preparation of bovine serum albumin conjugate and beta-galactosidase labelled antigen for enzyme immunoassay of 3 beta (monoglucuron-1' beta-yl)-18 beta-glycyrrhetic acid. AB - In order to prepare an immunogen for enzyme immunoassay of 3 beta-(monoglucuron 1'-beta-yl)-18 beta-glycyrrhetic acid (3MGA), which was isolated from a patient with glycyrrhizin-induced pseudoaldosteronisms, benzyl glycyrrhetate (3) was allowed to react with an acetobromosugar (2) in the presence of silver carbonate to give benzyl 3 beta-(methyl 2',3',4'-triacetyl-glucuron-1' beta-yl) glycyrrhetate (5) and methyl 3',4'-diacetyl-alpha-1',2'-O-[1-(benzyl glycyrrhet-3 beta-yl)- ethylidene]-D-glucuronate (4). On the other hand, this reaction was carried out in the presence of mercuric cyanide in nitromethane to give compound 5, benzyl 3 beta-acetyl glycyrrhetate (6) and benzyl 11-oxo-A-neooleana-3(5),12 dien-3-oate (7). 4-Aminomethylcyclohexanecarboxylic acid and glycine were introduced as chemical bridges at C-30 of 3 beta-(tert-butylglucuron-1' beta-yl) glycyrrhetic acid (11) derived from compound 5. The former bridge was used to prepare an immunogenic conjugate with bovine serum albumin, and the latter bridge was used for antigen labelled with beta-galactosidase. PMID- 2110869 TI - Establishment and characterization of cell lines (Kagura-1 and Kagura-2) from aflatoxin B1-induced rat hepatoma. AB - Two hepatoma cell lines designated Kagura-1 and Kagura-2 were established from rat hepatocellular carcinomas induced by aflatoxin B1, and have been propagated for over two years. Both cell lines grew as monolayered sheets with a population doubling time of about 20 h. Chromosome counts of Kagura-1 cells ranged from 34 to 45 with a modal number of 40, while that of Kagura-2 cells ranged widely from 40 to 130 with a modal number of 65. Subcutaneous inoculation of cultured cells of both these lines into nude mice resulted in tumor formation. The histopathological appearances of the induced tumors were similar to those of the original tumors. Kagura-1 and Kagura-2 cell lines express at least two tumor markers, glutathione-S-transferase P and gamma-glutamyl transpeptidase; the level of c-myc messenger ribonucleic acid was also highly elevated. PMID- 2110870 TI - Pharmacokinetics in chimpanzees of recombinant human tissue-type plasminogen activator produced in mouse C127 and Chinese hamster ovary cells. AB - Pharmacokinetics of recombinant tissue-type plasminogen activator (rt-PA) produced in mouse C127 cells (t-PA(C127] and Chinese hamster ovary cells (t PA(CHO] was investigated in chimpanzees. rt-PA was administered via a constant rate i.v. infusion for 60 min, and t-PA concentration and activity in plasma were measured during and after infusion. The noncompartmental parameters were calculated according to the moment analysis method, and a population pharmacokinetic analysis was performed to obtain the mean and interindividual variability of the pharmacokinetic parameters. The mean residence time of t PA(C127) was significantly longer and the total body clearance was significantly less than that of t-PA(CHO). t-PA(C127) has an alpha-galactosyl moiety in its carbohydrate chains, whereas such a structure is not found in t-PA(CHO). These results demonstrate that two preparations of rt-PA's with different carbohydrate structures show different pharmacokinetics, and suggest that the carbohydrate structure can affect the efficiency of hepatic uptake of t-PA. A possible mechanism is an interaction of t-PA(C127) with the natural anti-alpha-galactosyl antibody. The anti-alpha-galactosyl antibody level in plasma decreased in association with the plasma levels of t-PA(C127) but was unaffected by t-PA(CHO) levels. PMID- 2110871 TI - Optimized preservation of isoforms of creatine kinase MM isoenzyme in plasma specimens and their rapid quantification by semi-automated chromatofocusing. AB - We report a convenient chromatofocusing procedure for rapid and sensitive quantification of isoforms of the MM isoenzyme of creatine kinase (EC 2.7.3.2) in plasma and efficient methods for preserving isoform profiles during handling of specimens. The assay involves use of prepacked, re-usable Mono P chromatofocusing columns and a "Fast Protein Liquid Chromatograph" (FPLC) system with on-line detection of isoform enzymatic activity in column effluent. Profiles of isoforms are analyzed within 25 min with the use of a 1-mL column; the lower limit of sensitivity for CK activity is 5 mU, and recovery of each isoform is within 1% of the amount added to plasma. Collection of blood specimens in Vacutainer Tubes containing 28.5 mumol of EDTA (final concentration in plasma, 7 to 10 mmol/L) inhibited carboxypeptidase activity in plasma by 76%, sufficient to essentially abolish isoform conversion in vitro at room temperature. These methods should facilitate applications of isoform analysis for diagnosis of myocardial infarction and coronary artery recanalization. PMID- 2110872 TI - Evaluation of long-term frozen storage of plasma for measurement of high-density lipoprotein and its subfractions by precipitation. AB - The concentration of high-density lipoprotein cholesterol (HDL-C) in plasma is now established as an independent risk factor for coronary heart disease, but more data are needed on the relative risk-predictive powers of different HDL subclasses. For epidemiologic and clinical purposes, isolation of HDL from other lipoproteins and separation of its two major subclasses, HDL2 and HDL3, are performed most conveniently by precipitation. Although storage of plasma is commonly necessary, little information is available on the long-term stability of HDL subclasses at different temperatures. Therefore, we quantified HDL-C, HDL2-C, and HDL3-C by dual precipitation with heparin-MnCl2/15-kDa dextran sulfate (H M/DS) in samples of EDTA-plasma from 93 healthy subjects, after storage for one to 433 days at -20 degrees C, at -70 degrees C, or in liquid nitrogen (-196 degrees C). Fourteen samples (15%) were stored for a year or longer. At -20 degrees C, HDL-C decreased by 4.8% per year and HDL3-C decreased by 6.9% per year (P = 0.002 for both variables) relative to results obtained with samples stored in liquid nitrogen; total cholesterol, HDL2-C, and triglyceride did not change significantly at this temperature. When stored at -70 degrees C, none of the lipids showed any change relative to results obtained with liquid nitrogen. Thus, long-term storage of EDTA-plasma at -20 degrees C is unsuitable for subsequent quantification of HDL-C and its subclasses by H-M/DS dual precipitation. Storage at -70 degrees C is preferable, and is as reliable as storage in liquid nitrogen. PMID- 2110873 TI - Rapid and simultaneous determination of lactulose and mannitol in urine, by HPLC with pulsed amperometric detection, for use in studies of intestinal permeability. AB - The lactulose/mannitol dual sugar absorption test is a non-invasive test of intestinal permeability. Its widespread use has been limited by the difficulties of analysis for carbohydrates in urine at low concentrations. We describe a "high pressure" liquid-chromatographic method for determining lactulose and mannitol in urine, in which anion-exchange chromatography and pulsed amperometric detection are used. Sample preparation is simple and fast, and lactulose and mannitol and the internal standards arabinose and cellobiose are well resolved within 15 min. Analytical response of the method is linear with concentrations to 3 g/L, and one can detect as little as 0.3 mg of lactulose per liter of urine. Analytical recovery was between 90% and 107% for all sugars analyzed, and there was good agreement with results by a gas-chromatographic method (r = 0.993 lactulose, 0.984 mannitol). The method may potentially be applied to the study of other carbohydrates present in biological fluids at low concentrations. PMID- 2110874 TI - New ultrafiltration method for free thyroxin compared with equilibrium dialysis in patients with thyroid dysfunction and nonthyroidal illness. AB - This new ultrafiltration method for free thyroxin in serum [FT4(U)] is based on radioimmunoassay of the free hormone fraction in ultrafiltrates obtained by centrifuging serum samples in Unisep Ultracent-10 ultrafiltration devices. We compared the results obtained with those by an equilibrium dialysis method [FT4(D)]. In 36 euthyroid healthy subjects, the mean FT4(U) concentration was 24.2 pmol/L and the mean FT4(D) concentration 14.8 pmol/L. In hyperthyroid and hypothyroid patients, results by the ultrafiltration method were also approximately twice as high as those obtained by the dialysis method. In 23 patients with various nonthyroidal illnesses, mean FT4(U) was 41.2 pmol/L and mean FT4(D) 19.8 pmol/L. The mean FT4(U)/FT4(D) ratio in patients with nonthyroidal illnesses (1.97) was not significantly higher than in control subjects (1.68), making it unlikely that the increase in serum FT4 is caused by weakly protein-bound and therefore dialyzable inhibitors of thyroxin binding to carrier proteins. However, two nonthyroidally ill patients with a clearly increased FT4(U) but a normal FT4(D) concentration might have had such inhibitors, whereas for two other nonthyroidally ill patients a high molar ratio of free fatty acids to albumin is a more likely explanation for increased FT4(U) and FT4(D) concentrations. On theoretical grounds, we consider the FT4(U) concentrations analytically more nearly accurate than FT4(D) values for all patient groups studied. PMID- 2110875 TI - Effect of serum albumin on in vitro displacement of valproic acid by ceftriaxone and nafcillin. PMID- 2110876 TI - Significance of the intestinal gradient of diamine oxidase activity. PMID- 2110877 TI - Parenteral methotrexate or gold for rheumatoid arthritis: a follow up. AB - The forty participants in a double blind controlled trial of parenteral methotrexate or gold for RA were followed up two years later. Fifty percent had remained on the original medication, 13/20 on MTX and 7/20 on gold. Only 5 and 3 of them respectively had no active joint swelling. No major differences between the two groups were seen. PMID- 2110878 TI - Comparison of inhibitory and bactericidal activity of antipseudomonal antibiotics against Pseudomonas aeruginosa isolates from cystic fibrosis patients. AB - Using a broth microtiter dilution method, the minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) of so-called antipseudomonal antibiotics were determined against 79 Pseudomonas aeruginosa isolates from cystic fibrosis patients. On the basis of the MIC values and using DIN breakpoints, the percentual susceptibilities led to the following rank order: imipenem (91%), ciprofloxacin (90%), tobramycin (87%), amikacin (87%), ceftazidime (82%), cefsulodin (76%), piperacillin (71%), azlocillin (62%), followed by gentamicin, ceftriaxone, mezlocillin, netilmicin, and cefotaxime (less than 50%). However, evaluating MBC values according to DIN breakpoints, only ciprofloxacin (82%), tobramycin (77%), amikacin (58%), and imipenem (57%) showed a pronounced antipseudomonal effectiveness. The data indicate that MBC determinations are necessary to evaluate the antibiotic susceptibility of P. aeruginosa rather than MIC determinations, at least in patients with impaired defence mechanisms which require bactericidal therapy. PMID- 2110879 TI - [Intratumoral injection of mitomycin for adenocarcinoma of the duodenum]. PMID- 2110880 TI - [Lactate acidosis during parenteral nutrition]. PMID- 2110881 TI - Organic micropollutants in lakes: a sedimentological approach. AB - Many very persistent and lipophilic compounds, considered to be of concern for chronic toxicity and bioaccumulation, are generally present in surface waters at very low and variable concentrations. Sediments represent a concentrated pool for these compounds and consequently they are often analyzed instead of water. Some theoretical models have been proposed recently (Hakanson, 1980; Galassi and Migliavacca, 1986; Provini et al., 1987) in order to estimate the concentration of these pollutants in water and their potential risk for aquatic biota and human health. In this work sediments from three subalpine lakes located in Northern Italy, very close to each other but with different anthropogenic loads, were collected at several stations for determination of the classes of organic micropollutants of urban, industrial, and agricultural origin. Results show that urban and industrial pollution are predominant in this area. Two classes of micropollutants seem to be most related to anthropogenic activities: PAH and trichloroalkylphosphates. The first reaches lake sediments through atmospheric deposition and point sources; the second, present only in two lakes, is more likely to be due to industrial effluents. The advantages and limitations of the sedimentological approach for risk assessment in the aquatic environment are discussed. PMID- 2110882 TI - Headspace determination of evolved carbon dioxide in a biodegradability screening test. AB - A headspace method to measure the carbon dioxide evolved in a screening biodegradability test is described. Use was made of conventional serum bottles, sealed with butyl rubber septa, through which headspace samples were taken after acidification and equilibration of the test solution. For each determination a serum bottle was sacrificed. The gas samples were injected directly into the reaction chamber of a carbon analyzer. Eighteen chemicals varying in solubility and biological properties were submitted to the test. Where possible, mineralization of test compounds was monitored through dissolved organic carbon analysis in addition to CO2 analyses. The reliability of the method was verified by comparing the measured concentration of dissolved inorganic carbon of a standard sodium carbonate solution with values calculated from measured concentrations of carbon dioxide in the headspace after acidification. Results of biodegradability testing are discussed in view of the suitability of the method to poorly soluble compounds. PMID- 2110883 TI - [Spreading depression--cortical reactions: disorders of the extracellular microenvironment]. AB - Changes of brain cell microenvironment in the cerebral cortex of the rat were studied during spreading depression (SD) elicited by KCl application or local cooling. The question was whether the behavior of extracellular ion concentrations, especially of K+, could give some information about the triggering mechanisms of SD at the site where the phenomenon originates in the tissue. SDs elicited by KCl and recorded far from their original sites were associated with disturbances of extracellular ion concentrations and of tissue pO2 and pCO2 showing characteristic time sequences. Under these conditions none of the parameters studied changed before SD development. When an SD was elicited by local cooling extracellular K+ concentration ([K+]0) increased steeply in the mostly cooled cortical layers prior to SD initiation and formed a plateau of about 10 mmol/l resembling the ceiling level for K+ associated with ictal seizure activity. The front of the SD wave moved down slowly to the white matter. Thereby the rectangular rise in [K+]0 prior to SD progressively flattened and finally disappeared. The results suggest that SD evoked by local cooling originates from a primary increase of [K+]0 to the K+ ceiling level and by a secondary breakdown of the mechanisms being responsible for this type of K(+)-regulation. The mechanisms mentioned may be responsible for all kinds of SD-triggering. PMID- 2110884 TI - [Automatic sleep analysis. I. Scoring of parameters]. AB - EEG, EOG, EMG and motility are recorded and preprocessed by hardware filtering of EEG and hardware detection of sigma spindles, rapid eye movements (REMs) and delta-waves (greater than 45 microV). After AD-conversion calculation of mean values and smoothing, the sleep-wake-process can be represented by the time curves of 8 parameters: mean amplitudes per epoch (30 s) of EMG, motility and EEG (in the delta- alpha- and beta-band), delta-time (time/epoch of counted delta waves) and presence or absence of spindles and REMs per epoch. These parameters can be presented graphically or stored for further analysis of sleep stages, sleep structure or sleep periodicity. PMID- 2110885 TI - [Possibilities and limitations of the automatic analysis of sleep stages using the Oxford system]. AB - 34 ambulatory polygraphic sleep-records of young adults were carried out using the Oxford Medilog 9000 recorder. All of the records underwent automatic evaluation by the Oxford Sleep Stager. 10 cases were, in addition, evaluated visually. 4 records could not be analyzed because of artifacts. Thus, 30 subjects were used in the end for establishing standard values of sleep parameters. Automatic versus automatic comparisons and automatic versus visual comparisons of ten polysomnograms were performed epoch-by-epoch. The automatic versus automatic comparison showed agreement in 85.5% of epochs, and the automatic versus visual comparison in 70.4% of epochs. The Sleep Stager showed the best agreement with the visual evaluation in epoch-by-epoch comparison in the REM-stage (93.9%), the worst in stage 1 (32.4%). In calculating the percentages of total night sleep for the respective sleep stages, the automatic analysis showed strongest disagreement with visual evaluation in the REM-stage (plus 7.5%) and in stage 2 (minus 5.2%). PMID- 2110886 TI - [Multimodal evoked potentials and heart rate variability in comatose patients. 3. Electrophysiologic findings in inflammatory diseases of the brain]. AB - Multimodal evoked potentials and heart-rate variability (HRV) measurements were performed in a total of 15 comatose patients with inflammatory diseases of the brain. The following potentials were recorded: Brainstem auditory evoked potentials (BAEP), early (SSEP) and long latency (SEP) somatosensory evoked potentials and visual evoked potentials (VEP). The results of the initial BAEP recordings indicate that in 83% of the patients the IV-V interpeak latency was prolonged and out of the range of normal values. Additionally an atypical form of the IV-V wave complex was detected. The SSEP after electrical stimulation demonstrated pathological findings in 90% of the patients; long latency components after mechanical vibration could be identified only by 30%. The results of the VEP show an attenuation of vertex VEP (mean value: 43%). Heart rate variability of the patients was calculated (mean +/- SD) to be 2.5 +/- 1.4% (norm: 7.8 +/- 2.5%) with a mean heart-rate of 95.2 +/- 16.6/min (norm: 67.8 +/- 10.7/min). PMID- 2110887 TI - [Simulated epileptiform discharges during the replay of a lengthy EEG recording]. AB - Reviewing a longterm-EEG magnet-recording on the video system of the play-back unit "Mobile Oxford Medilog 9000" EEG patterns appeared, which imposed as epileptiform discharges. They seemed to correlate with the paroxysmal clinical disturbances the patient had experienced and noted in a diary, and could be printed out on a normal EEG-apparatus. Following investigations demonstrated the artificial origin of this EEG patterns: They appeared in fact only using the switches of the play-back unit for the fast back- and forward winding. The time correlation between clinical and electroencephalographic episodes was simulated by the search of selected EEG-sequences based on the clinical episodes noted from the patient. PMID- 2110888 TI - [Methodology and diagnostic potentialities of macro-EMG. I. Methodology]. AB - Macro-EMG records electrical activity from the whole motor unit (MU) as a parameter of its size. The main component of the recording device is a modified single fiber or concentric needle electrode. Different sized uptake areas allow to record with different selectivities from the MU. The teflon insulated shaft surface allows to record with a defined large blank area unselectively macro signals from the muscle. The conceptual ideas to use a concentric needle in addition to the single fibre electrode is to simplify the trigger-potential recording, which needs to be selective within the MU. In both instances the EMG apparatus has to provide two channels, one for the trigger and the second for an averaging device to record the macro-EMG. The different techniques use the single fiber or concentric EMG-potential as a trigger to average the associated macro potential from the raw signals. The electrodes different design allow the whole single-fiber-needle to lie within the MU territory whereas the MU is only touched by the concentric needles tip. This implies different recording situations and results. Anatomically macro-EMG size is varied by the recording site of the muscle. The signal is greater close to the endplate zone and declines to stable values about 20 mm apart. For quantitative measurements within a muscle 20 different potentials have to be evaluated for median amplitude, duration and area. PMID- 2110889 TI - [Motor neurography: simultaneous recording using surface and needle electrodes. A comparative study of the proximal and distal latency together with the motor nerve conduction velocity]. AB - The generally accepted interpretation that the application of surface and concentric needle electrodes for the recording of evoked muscle action potential in motor nerve neurography showed the same results has been reconsidered, especially because until now, over 20 years after the introduction of this neurophysiological method in routine clinical work, no exact statistically verified examinations have been done on this subject. Proximal and distal latency as well as motor nerve conduction velocity were determined in the following nerves in 100 subjects (71 healthy subjects and 29 patients): tibial, peroneal, ulnar, median. All neurographic parameters were obtained by means of simultaneous recording with surface and concentric needle electrodes and compared with one another. Concerning the ulnar nerve no statistically significant differences could be found. In the remaining three nerves, statistically significant differences could be detected for distal and proximal latency but not for motor nerve conduction velocity. PMID- 2110890 TI - [The significance of EMG artefacts in isoelectric EEG]. AB - Five potential organ donors showed muscle artefacts during isoelectrical EEG recording. The electromyographic examination revealed MUAP activity occurring as doublets, triplets and quadruplets. All patients had normal blood chemistry except reduced CO2 and increased O2 partial pressures. We assume that the recorded "tetaniform" muscle activity is due to hyperexcitability of the nerve membrane caused by artificial hyperventilation. PMID- 2110891 TI - [The cervical somatosensory evoked potential in lesions of the cortical efferents]. AB - Cervical and cortical somatosensory evoked potentials to median nerve stimulation were analysed in 20 patients with unilateral central paresis of the arm. Neither the configuration nor the latency and amplitude measures of the neck potential did reveal any association with pathological alterations of cortical efferents or with abnormal cortically evoked responses. Thus, also in this population the evaluation of cervical potentials can be done according to the known criteria. PMID- 2110892 TI - [Visual evoked discrimination potentials in childhood]. AB - 70 children without visual, developmental or neurological handicap in the age of 3 to 92 months were investigated. Using red and white light flashes non-target event-related evoked potentials have been registrated, white light serving as rare (20%) stimulus (Fig. 1 and 5). It could be shown that in the event-related potential the peak latencies from N3 on had a significantly shorter latency than under red- or pure white-light stimulation (Fig. 2). They were called discriminative potentials. Diagrams (Fig. 4) revealed a maturating course with increasing age by decreasing latencies of the discriminative peaks. Normal values (Table 1) were compiled in order to serve as diagnostic criteria in diagnosis and follow-up of cerebral affections in early childhood. PMID- 2110893 TI - [Generalized nocifensive reflexes. I. Methodologic bases]. AB - Normal protective and defence reflexes show that the nocifensive system is intact. Nocifensive reflexes can be modified by various brainstem disturbances, and in the case of lesions the symptoms may appear in the afferent or efferent section of the reflex arc. The purpose of our study was to find a method for evoked generalized nocifensive reflexes so that inferences regarding the course of the reflex could be drawn from a reflex pattern obtained from the latent periods of various lead regions during nocifensive stimulation. The stimulus is provided by a painful train of electrical pulses applied to a superficial nerve (N. medianus, N. fibularis). As a rule, the leads are connected symmetrically to the flexors of the upper and lower extremities. The results shown, as expected, that nocifensive reactions fulfill the conditions of a conditioned reflex with increasing habituation and sensitization. The reflex arc passes through the formatio reticularis, and it is here in particular that cerebral influences can have a modulatory effect. These conclusions are based on the length of the latent times, which are longer than those associated with spinal reflexes, but shorter than the reaction times shown by the voluntary innervation. Moreover, the reflex patterns observed for the upper and lower extremities are identical for different stimulation sites, so the reflex circuit must be supraspinal. Since, in addition, the reflex pattern associated with acoustic stimulation is similar to that of an electrically evoked reflex, the formatio reticularis can be considered a nocifensive centre. PMID- 2110894 TI - [Transarterial EEG in superselective cerebral angiography]. AB - Transarterial EEG-recording is a complementary method to surface and depth techniques. In 8 patients having superselective angiography because of diagnosis or therapeutic manoeuvres transarterial EEG-recording was performed. There were only few artefacts and no clinical side effects. The value of this additional information is discussed. PMID- 2110895 TI - Structural features of neutral protease from Bacillus subtilis deduced from model building and limited proteolysis experiments. AB - The overall folding of neutral protease from Bacillus subtilis has been predicted by computer-aided modelling, taking as a basis the known three-dimensional structure of thermolysin. As expected from the 50% similarity of sequence between the two proteins, the structure of B. subtilis protease is similar to that of thermolysin, including the two-domain topology and location of elements of regular secondary structure (helices and strands), whereas specific differences were predicted in loop regions. A protruding and loose loop predicted in B. subtilis has been detected also experimentally by a limited proteolysis approach. Incubation of B. subtilis protease at pH 9.0 for 24 h at room temperature with trypsin at 20:1 ratio (by mass) leads to a specific and almost quantitative fission of the Arg214-Asn215 peptide bond located in a highly exposed, and thus probably flexible, loop of the protease. On the other hand, thermolysin was completely resistant to tryptic hydrolysis when reacted under identical conditions. The 'nicked' B. subtilis protease can be isolated by gel filtration chromatography at neutral pH, whereas the two constituting fragments 1-214 and 215-300 are separated under protein-denaturing conditions. Overall, these results indicate that the limited proteolysis approach can pinpoint a peculiar difference in surface structure between the two similar protein molecules of B. subtilis neutral protease and thermolysin and emphasize the potential use of proteolytic enzymes as structural probes of globular proteins. PMID- 2110896 TI - The effect of von Willebrand factor on activation of factor VIII by factor Xa. AB - Factor VIII has to be activated before it can serve efficiently as a cofactor in the intrinsic pathway of blood coagulation. This activation occurs through specific proteolytic cleavages in the molecule by either thrombin or factor Xa. In this study, we show that von Willebrand factor inhibits the activation of factor VIII by factor Xa. Incubation of factor VIII (30 U/ml) with 0.1 microgram/ml factor Xa resulted in a 1.6-fold activation followed by a decay of coagulant activity. In the presence of 10 micrograms/ml von Willebrand factor, activation and inactivation of factor VIII was completely inhibited. In contrast, the activation of factor VIII by thrombin was not influenced by von Willebrand factor. At high concentrations of factor Xa (10 micrograms/ml), von-Willebrand factor-bound factor VIII could be cleaved and activated. The generated proteolytic fragments were identical to the fragments produced in the absence of von Willebrand factor and all fragments were released from von Willebrand factor. The major products were light-chain-derived fragments of molecular mass 66/68 kDa and 60 kDa and heavy-chain-derived fragments of 40 and 42 kDa. Also minor products of 12, 20/21, 23, 27 and 30 kDa were observed, most of which were specific for cleavage of factor VIII by factor Xa. PMID- 2110897 TI - 4-Phenyl-3-butenoic acid, an in vivo inhibitor of peptidylglycine hydroxylase (peptide amidating enzyme). AB - The ability of a series of non-peptide carboxylic acids to act as substrates or inhibitors of the peptide-amidating enzyme (peptidyl-glycine hydroxylase) was assessed by determining their ability to reduce the rate of enzymic conversion of D-tyrosyl-valyl-glycine or D-tyrosyl-phenylalanyl-glycine to the corresponding dipeptide amide. The inclusion of a phenyl substituent in a position distal to the carboxyl group promoted the inhibitory action. The inhibition was found to be irreversible when an olefinic double bond, alpha or beta to the carboxyl group, was present in the molecule; the inhibition appeared to be associated with a covalent interaction between the amidating enzyme and the inhibitor. With 4 phenyl-3-butenoic acid the inhibitory properties were manifest only in the presence of cofactors of the enzyme. When 4-phenyl-3-[2-14C]butenoic acid was used, the radioactivity was shown to be incorporated into protein that co chromatographed with active enzyme. Incubation of rat thyroid carcinoma CA77 cells in the presence of 4-phenyl-3-butenoic acid led to a decrease in the levels of intracellular amidating activity and of thyrotropin-releasing hormone, an amidated peptide produced by these cells. The inhibitory effects reached a maximum at approximately 15 h after which the enzyme levels returned to the control values even though the concentration of 4-phenyl-3-butenoic acid in the cells remained unchanged. The results indicate that a mechanism exists in these cells for regulation of amidating activity. PMID- 2110898 TI - Limited proteolysis of beta 2-microglobulin at Lys-58 by complement component C1s. AB - We have now demonstrated that activated complement component C1s cleaves beta 2 microglobulin at the position identical to that at which beta 2-microglobulin is cleaved in serum of patients suffering from lung cancer. The main cleavage is in the disulphide loop C-terminal to Lys-58, generating a modified form of beta 2 microglobulin with a two-chain structure. The C-terminal Lys-58 in the A chain is highly susceptible to removal by a carboxypeptidase-B-like activity causing the formation of des-Lys58-beta 2-microglobulin. This is the first demonstration of a noncomplement protein substrate for the proteolytic activity of C1s. The C1s induced cleavage of beta 2-microglobulin can be inhibited in the presence of C1 esterase inhibitor, demonstrating a regulatory function of C1 esterase inhibitor in the C1s-induced cleavage of beta 2-microglobulin. PMID- 2110899 TI - A point mutation in the tyrosinase gene of BALB/c albino mouse causing the cysteine----serine substitution at position 85. AB - Murine albinism is characterized by complete lack of melanin pigments in skin and retina. In order to study the molecular basis of albinism, we have cloned and characterized the tyrosinase gene of BALB/c mice (c/c). Sequence analysis of this gene reveals a point mutation at nucleotide residue 387 (G----C transversion) causing a Cys----Ser substitution at position 85 in one of the cysteine-rich domains of the tyrosinase molecule. Since this G----C transversion creates an additional DdeI site, we were able to confirm that this mutation is actually present in BALB/c genomic DNA using DNA amplification techniques. In contrast, both C57BL/6 (C/C) and DBA/2 (C/C) mouse strains carry the G residue at the same position, suggesting that this point mutation is specific for the albino mutation at the c locus. Moreover, we were able to show that the tyrosinase containing Ser 85 is not functional in transient expression of its cDNA. We therefore suggest that a G----C transversion at nucleotide residue 387 of the tyrosinase gene could lead to the albino phenotype of BALB/c mouse. PMID- 2110900 TI - In vitro bactericidal activity of amoxicillin, gentamicin, rifampicin, ciprofloxacin and trimethoprim-sulfamethoxazole alone or in combination against Listeria monocytogenes. AB - The in vitro bactericidal activity of amoxicillin, gentamicin, rifampicin, ciprofloxacin and trimethoprim-sulfamethoxazole alone or in combination was determined against seven strains of Listeria monocytogenes by the killing curve method. Amoxicillin plus gentamicin was the most rapidly bactericidal combination, whereas trimethoprim-sulfamethoxazole was less bactericidal at 6 h but as bactericidal at 24 h. The combination of trimethoprim-sulfamethoxazole with either amoxicillin, ciprofloxacin or rifampicin did not result in antagonism, but the combinations were no more active than trimethoprim sulfamethoxazole alone. The interaction of amoxicillin with rifampin was fairly antagonistic (1 log10 difference). The combination of amoxicillin and ciprofloxacin, although producing antagonism during the first 6 h, was more active at 24 h than amoxicillin alone and prevented the regrowth observed with ciprofloxacin alone. Ciprofloxacin and rifampicin interacted antagonistically during the first 6 h, and the combination was not very bactericidal (3 log10) but prevented the emergence of mutants, as observed with each drug alone, when used at concentrations greater than the MICs for the strain tested. These regimens merit evaluation in in vivo models of Listeria monocytogenes meningitis. PMID- 2110901 TI - Distribution of serovars of Listeria monocytogenes isolated from different categories of patients with listeriosis. AB - An analysis was made of the distribution of serovars of Listeria monocytogenes isolated from 1363 patients with listeriosis. Overall, serovar 4b was found in 64% of cases, serovar 1/2a in 15%, serovar 1/2b in 10%, and serovar 1/2c in 4%. The patients were categorised as pregnancy associated cases, non-pregnant previously healthy cases, and non-pregnant cases with severe underlying illness. The serovars were unequally distributed between these three groups of patients. Serovar 1/2b occurred most often in the non-pregnant cases with severe underlying illness, and serovar 1/2c occurred least frequently in the pregnancy associated cases. Serovar 4b occurred more often in the pregnancy associated cases than in previously healthy non-pregnant cases, and more often in the latter than in those with underlying illness. Similar distributions of the serovars between the categories of patients occurred over different time periods. These results may be interpreted as indicating an association between virulence and serological type of Listeria monocytogenes. PMID- 2110902 TI - Diagnosis of Mycoplasma pneumoniae infection by microparticle agglutination and antibody-capture enzyme-immunoassay. AB - The performance of two new commercial assays for the serological diagnosis of Mycoplasma pneumoniae infection (microparticle agglutination and antibody-capture enzyme-immunoassay) was studied using a panel of 169 serum samples from patients with Mycoplasma pneumoniae pneumonia and a control group. Both assays were shown to be sensitive and specific for diagnosis. The performance of the capture immunoassay, however, decreased in older patients, probably due to its inability to detect cases of reinfection without IgM antibody response. PMID- 2110903 TI - Evaluation of a commercial enzyme immunoassay for detection of Mycoplasma pneumoniae specific immunoglobulin G antibodies. AB - A commercial enzyme immunoassay (Platelia Mycoplasma, Diagnostics Pasteur) for the diagnosis of Mycoplasma pneumoniae [corrected] infections was evaluated and found not to be suitable for the purpose. More than 80% of healthy persons and patients with non-Mycoplasma pneumoniae respiratory infection, all with a negative Mycoplasma pneumoniae complement fixation test, had a positive EIA. Paired sera did not show the positive correlation between a rise in complement fixation titre and the EIA ratio reported by the manufacturer. PMID- 2110904 TI - Rapid immunoblot method for diagnosis of acute Mycoplasma pneumoniae infection. AB - A rapid immunoblotting technique based on the IgM response to a major immunogenic protein is described for the diagnosis of Mycoplasma pneumoniae infection. Using results of the complement fixation test as the criterion for diagnosis, the rapid immunoblot method was positive in 95.7% of patients. The sensitivity was reduced to 81.9% if the test was performed on either single sera or acute sera only from serum pairs. Although the few sera that failed to demonstrate a positive IgM response were more likely to be from older patients, there was a consistent IgM response recorded for both younger (less than 20 years) and older (greater than or equal to 20 years) patients. PMID- 2110905 TI - In vitro activity of cefpirome (HR810) against Enterococcus species. PMID- 2110906 TI - Ranolazine (RS-43285): a preliminary study of a new anti-anginal agent with selective effect on ischaemic myocardium. AB - Ranolazine (RS-43285) has been shown to possess significant anti-ischaemic properties in a canine model of reversible myocardial ischaemia. The clinical efficacy of this new agent was assessed by a single blind, placebo controlled study of 14 patients with chronic stable angina. A 2 week placebo phase was followed by therapy with 30 mg and 60 mg of ranolazine tid for 2 weeks each. Graded, symptom limited treadmill exercise tests were performed at the end of each phase, 1.5 h (AM) and 7 h (PM) after the morning dose. An additional exercise test 1.5 h after the first dose of 30 mg was included to assess the acute dose response. In the AM study, the mean exercise time increased from 6.9 min (placebo) to 7.8 min after the first dose of 30 mg and to 8.2 min and 8.5 min respectively at the end of 30 mg and 60 mg phases. In the PM study, exercise time improved from 6.5 min (placebo) to 8.2 min and 7.8 min respectively at the end of 30 mg and 60 mg phases. The time to onset of angina showed a similar improvement. No significant changes were observed in the resting and peak exercise heart rates and blood pressure. This preliminary study suggests that ranolazine may significantly prolong exercise time in patients with stable coronary artery disease without altering heart rates and blood pressure. PMID- 2110907 TI - Diabetes-related histopathologies of the rat retina prevented with an aldose reductase inhibitor. AB - Recent evidence obtained from both galactosemic dogs and rats indicated that aldose reductase inhibitors could prevent several capillary lesions which were similar to those typical of diabetic retinopathy in humans. The present study demonstrates that diabetes-like histopathological changes in the intact retina, which were not visible in the vessel whole mounts used previously, can also be prevented. Sprague-Dawley rats were fed diets containing 50% galactose with or without an aldose reductase inhibitor (tolrestat). After 28 months of galactose feeding, the findings from retinal transections examined by light and electron microscopy were consistent with reports on vessel whole mounts, but showed several additional changes. There was a marked increase in the thickness of the retinal inner limiting membrane, as well as in the capillary basement membranes. There was extensive gliosis and disruption of retinal layers as well as pericyte degeneration, endothelial cell proliferation, accellularity, capillary dilation, and microaneurysm formation. The contents of pericyte compartments in the capillary wall were often replaced with non-pericyte cytoplasm, which appeared glial cell-like. Many of the lumens of acellular capillaries were occluded with debris from degenerating endothelial cells or with cytoplasm possibly originating from glial cell processes. Structures suggestive of degenerated microaneurysms were present mainly in the inner nuclear and outer plexiform layers. The microaneurysms and other major changes were limited to the central and paracentral retina. All these retinal lesions were prevented with orally administered tolrestat. Thus, long-term galactosemia in rats induced histopathologically visible angiopathies, simulating those occurring in background diabetic retinopathy in humans, and these were prevented by treatment with an aldose reductase inhibitor. PMID- 2110908 TI - In vitro non-enzymatic glycation and formation of browning products in the bovine lens alpha-crystallin. AB - Calf lens LMW alpha-crystallin was glycated by incubating with various sugars (glucose, glucose-6-P and ribose) for 21 days. All sugars induced disulfide formation, but ribose also produced higher molecular weight cross-linked species. The ribocated protein turned yellow in color and had a strong blue fluorescence (Ex/Em = 370/450 nm) typical for a browning product. The chromophore of the browning product showed a new circular dichroism (CD) band at 320-330 nm. Conformational study indicated that the browning reaction destablized protein and may play a significant role in protein aggregation and insolubilization. PMID- 2110909 TI - Inhibition of human granulocyte-macrophage colony formation by interleukin 2 treated lymphocytes is mediated by interferon gamma and tumor necrosis factor alpha. AB - We previously demonstrated that human granulocyte-macrophage colony (granulocyte macrophage colony-forming units, CFU-GM) formation was inhibited by interleukin 2 (IL-2)-treated lymphocytes and their conditioned medium (CM). In the present study, the mechanism of this suppression was investigated. When anti-interferon (IFN)-gamma antibody or anti-tumor necrosis factor (TNF)-alpha antibody was added to CFU-GM agar culture with IL-2-treated lymphocytes or their CM, the inhibition of CFU-GM colony formation was partially abrogated, whereas anti-TNF-beta antibody did not abolish the inhibitory effects. When anti-IFN-gamma and anti-TNF alpha antibodies were added simultaneously, full recovery of colony formation was observed. In the CM of IL-2-treated lymphocytes, detectable levels of IFN-gamma (81 +/- 15 U/ml) and TNF (3.1 +/- 1.1 U/ml) were found. Addition of IFN-gamma and TNF-alpha at these concentrations to the agar culture inhibited CFU-GM colony formation. Taken together, these results indicate that inhibition of human CFU-GM colony formation by IL-2-treated lymphocytes and their CM is mediated by IFN gamma and TNF-alpha generated from IL-2-treated lymphocytes. PMID- 2110910 TI - Evolutionary specificity of hydrins, new hydroosmotic neuropeptides: occurrence of hydrin 2 (vasotocinyl-Gly) in the toad Bufo marinus but not in the viper Vipera aspis. AB - Hydrin 2 (vasotocinyl-Gly), a hydroosmotic peptide resulting from differential processing of provasotocin and recently identified in frog neurohypophysis, has been looked for in the pituitary gland of an exotic toad (Bufo marinus) and of a reptile (Vipera aspis). Hydrin 2 has been found in the amphibian but not in the reptile. This result confirms the evolutionary specificity of hydrin 2 that has been identified only in frogs and toads but not in birds and reptiles. Occurrence of hydrin 2 is explained by its regulatory function on the water permeability of the skin of anurans. PMID- 2110911 TI - Modification of a glnB-like gene product by photosynthetic electron transport in the cyanobacterium Synechococcus 6301. AB - Covalent modification of a 13 kDa soluble-phase protein occurs during adaptation of cells of the cyanobacterium Synechococcus 6301 (mutant AN112) to light specifically absorbed by photosystem II. This adaptation is accompanied by functional changes indicative of altered excitation energy distribution between the photosystems. The 13 kDa protein is identified by solid-phase N-terminal sequencing as a protein related to PII, the glnB gene product of E. coli. In E. coli, the PII protein undergoes uridylylation and acts as a regular of glutamine synthetase at both the post-translational and transcriptional levels. The implications of modification of a transcriptional regulator by photosynthetic electron transport are discussed. PMID- 2110912 TI - Expression in E. coli of the catalytic domain of rat poly(ADP-ribose)polymerase. AB - A 2 kilobase pair cDNA coding for the entire C-terminal catalytic domain of rat poly(ADP-ribose)polymerase has been expressed in E. coli. The overproduced 55 kDa polypeptide is active in synthesizing poly(ADP-ribose) and the 4 kDa N-terminal region of this domain is recognized by the monoclonal antibody C I,2 directed against the calf enzyme. Also, the minor alpha-chymotrypsin cleavage site found in the human catalytic domain is not present in the rat enzyme as revealed by the absence of the 40 kDa specific degradation product in the E. coli cells expressing the rat domain. The expression of this partial rat cDNA should thus permit the rapid purification and subsequent crystallization of the catalytic domain of the enzyme. PMID- 2110913 TI - Pertussis toxin-catalyzed ADP-ribosylation of a G protein in mouse oocytes, eggs, and preimplantation embryos: developmental changes and possible functional roles. AB - G proteins, which in many somatic cells serve as mediators of signal transduction, were identified in preimplantation mouse embryos by their capacity to undergo pertussis toxin-catalyzed ADP-ribosylation. Two pertussis toxin (PT) substrates with Mr = 38,000 and 39,000 (alpha 38 and alpha 39) are present in approximately equal amounts. Relative to the amount in freshly isolated germinal vesicle (GV)-intact oocytes, the amount of PT-catalyzed ADP-ribosylation of alpha 38-39 falls during oocyte maturation, rises between the one- and two-cell stages, falls by the eight-cell and morula stages, and increases again by the blastocyst stage. The decrease in PT-catalyzed ADP-ribosylation of alpha 38-39 that occurs during oocyte maturation, however, does not require germinal vesicle breakdown (GVBD), since inhibiting GVBD with 3-isobutyl-1-methyl xanthine (IBMX) does not prevent the decrease in the extent of PT-catalyzed ADP-ribosylation. A biologically active phorbol diester (12-O-tetradecanoyl phorbol 13-acetate, TPA), but not an inactive one (4 alpha-phorbol 12,13-didecanoate, 4 alpha-PDD), totally inhibits the increase in PT-catalyzed ADP-ribosylation of alpha 38-39 that occurs between the one- and two-cell stage; TPA inhibits cleavage, but not transcriptional activation, which occurs in the two-cell embryo (Poueymirou and Schultz, 1987. Dev. Biol. 121, 489-498). In contrast, cytochalasin D, genistein, or aphidicolin, each of which inhibits cleavage of one-cell embryos, or alpha amanitin or H8, each of which inhibits transcriptional activation but not cleavage of one-cell embryos, have little or much smaller inhibitory effects on the increase in PT-catalyzed ADP-ribosylation of alpha 38-39. Results of immunoblotting experiments using an antibody that is highly specific for alpha il 3 reveal the presence of a cross-reactive species of Mr = 38,000 (alpha 38) in the GV-intact oocyte, metaphase II-arrested egg, and one-, two-cell embryos. Relative to these stages, a reduced amount of this species is present in the eight-cell, morula, and blastocyst stages. Treatment of oocytes with PT results in a small but significant acceleration in the rate of GVBD, but has no effect on the extent of polar body emission. Treatment of one-cell embryos with PT has no effect on the extent of cleavage, onset of transcriptional activation at the two cell stage, or development of two-cell embryos to the hatching blastocyst stage. PMID- 2110914 TI - Topographical rearrangement of a plasma membrane antigen during capacitation of rat spermatozoa in vitro. AB - We have previously described an antigen (termed 2B1) on rat spermatozoa that is present on the plasma membrane overlying the tail domain. The antigen is mobile within the plane of the plasma membrane and a mAb to it blocks fertilization in vitro. In the present study we describe some dynamic properties of this antigen in relation to its topographical distribution. When spermatozoa were incubated in vitro in a capacitation medium and stained with 2B1 mAb/FITC-rabbit anti-mouse F(ab')2, strong fluorescence appeared over the acrosomal domain. Acute exposure of fresh spermatozoa to dissociating reagents (1 M NaCl or 5 mM 2 mercaptoethanol) or inducers of the acrosome reaction (lysolecithin + Ca2+ or A23187 + Ca2+) failed to mimic these effects. Spermatozoa prelabeled with FITC 2B1 IgG and then capacitated in the presence of excess "cold" 2B1 IgG also showed accumulation of fluorescence on the acrosomal domain, suggesting that the antigen had migrated from the tail. Migration was selective and Ca2(+)- and temperature dependent but was not inhibited by metabolic poisons (NaF or NaN3). Motility was not obligatory for migration. Immunogold-labeling studies at the ultrastructural level showed that 2B1 antigen was restricted to the surface membrane over both the tail and the acrosomal domains and that during migration it did not change the type of membrane into which it was inserted. From a quantitative analysis of fluorescence on spermatozoa prelabeled with FITC-2B1 IgG and then capacitated, the amount of antigen that appeared on the acrosomal domain was approximately equivalent to that lost from the midpiece domain. The Mr of 2B1 antigen extracted from capacitated spermatozoa was 300-500 Da less than that extracted from noncapacitated cells, suggesting that the molecule had undergone processing concomitant with migration. These results are discussed in relation to mechanisms for targeting antigens to sites where they become physiologically active and are correctly positioned to participate in gamete recognition processes. PMID- 2110915 TI - Transfer of cobalamin from the cobalamin-binding protein of egg yolk to R binder of human saliva and gastric juice. AB - Patients may fail to absorb cobalamin (vitamin B12) bound to food even when they have adequate intrinsic factor to absorb free cobalamin normally. We studied cobalamin transfer from egg yolk cobalamin-binding protein to human saliva and gastric juice as a model of this important first step in cobalamin assimilation. The cobalamin-binding protein of egg yolk eluted with human R binder on Sephadex gel chromatography and bound cobalamin with a comparable affinity, but it did not cross-react with R binder immunologically. Transfer of cobalamin from egg yolk to saliva or gastric juice R binder did not occur at neutral pH. Slight transfer (8% 12% of the 57Co-cobalamin bound to egg yolk) occurred when the saliva was acidified to pH 1.5. This minor transfer by acid was not inhibited by pepstatin A, a pepsin inhibitor. Acidification caused variable transfer to gastric juice R binder (12%-40%) that appeared to be partially due to residual gastric pepsin activity. Adding 1200 U of pepsin per milliliter enhanced cobalamin transfer to saliva or gastric juice R binders (39%-58% transfer). At no time was cobalamin transferred directly to intrinsic factor; R binder-deficient gastric juice failed to accept cobalamin from egg yolk. The transfer of cobalamin from egg yolk to human R binder requires both an acid pH and pepsin activity. While as little as 30 U of pepsin added per milliliter of saliva promoted transfer of cobalamin, the requirement for an acid pH was very strict. Virtually no transfer occurred when pH exceeded 2.0, regardless of the amount of pepsin present. Acid provided an optimal pH for pepsin activity and, to a lesser extent, affected transfer by a mechanism unrelated to pepsin. Our data suggest that compromised pepsin secretion and, probably even more importantly, compromised acid secretion interfere with transfer of food cobalamin to R binder. PMID- 2110916 TI - Postheparin plasma diamine oxidase in health and intestinal disease. AB - In animals, the distribution of the enzyme diamine oxidase is confined, almost exclusively, to the small bowel mucosa. In humans, plasma diamine oxidase is at or below assay detection limits but can be liberated into the circulation from binding sites in the intestine by i.v. heparin. Therefore, the authors wished to see if diamine oxidase could be released by a low and safe dose of heparin (5000 U) and if the resultant area under the concentration-time curve would provide a noninvasive marker of segmental intestinal disease. In 17 control subjects, the mean area under the curve (following administration of 5000 U i.v. heparin) was 35.9 +/- 5.0 (SEM) mU.L-1.2 h-1; in 6 individuals studied on two separate occasions, postheparin plasma diamine oxidase profiles were reproducible (r = 0.98; p less than 0.001). The longitudinal distribution of diamine oxidase in the gastrointestinal tract, measured in 12 gastric, 16 jejunal, 6 ileal, and 18 colonic biopsies, was similar in humans to that found in animals. In patients with normal peroral biopsies, there was a linear relationship between jejunal mucosal and postheparin plasma diamine oxidase activities (r = 0.84; p less than 0.01). The areas under the curve in controls were then compared with those in patients with segmental intestinal diseases: 21 with ileal disease with or without colonic Crohn's disease (10 unoperated and 11 with ileal resection), 7 with non-Crohn's ileal resection, 8 with ulcerative colitis, 10 with untreated and 7 with treated celiac disease (6 studied before and after a gluten-free diet), and 5 studied during total parenteral nutrition and again after resumption of oral feeding. The results in the 18 ileectomized patients were subdivided into those with major (arbitrarily greater than 75 cm) and minor (less than 75 cm) resections. Areas under the curve were markedly reduced in nonresected Crohn's patients (6.0 +/- 1.79 mU.L-1.2 h-1; p less than 0.001 vs. controls), correlating inversely, in a first-order relationship, with disease activity (r = 0.82; p less than 0.001) and returning toward normal in 4 patients achieving disease remission. Low areas under the curve in total parenteral nutrition patients (4.5 +/- 0.9; p less than 0.001) were also reversible on resumption of oral feeding. However, areas under the curve were not significantly lower in patients with limited ileal resection (less than or equal to 75 cm), with celiac disease (untreated and treated), or ulcerative colitis than in controls.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2110917 TI - Fetal liver disease may precede extrahepatic siderosis in neonatal hemochromatosis. AB - Three children of a mother with biopsy-confirmed posttransfusional hepatitis of undetermined etiology (non-A, non-B hepatitis) died in utero or in infancy. All had liver disease of intrauterine onset. The two liveborn children died of the consequences of severe hepatic insufficiency manifest at birth and met clinicopathologic criteria for neonatal hemochromatosis. Although hepatic architecture in the stillborn fetus was markedly disordered, with hepatocyte giant cell transformation, extrahepatic siderosis was not present and hepatic siderosis was minimal. These findings indicate that in some cases of neonatal hemochromatosis, extrahepatic siderosis may be caused by hepatic injury rather than primarily due to excessive transport of iron from mother to fetus and support speculation that in some instances an infective agent may be responsible. PMID- 2110918 TI - Brain peptides and duodenal bicarbonate. PMID- 2110919 TI - Reduction of thyrotropin-releasing hormone concentrations in central nervous system of African lungfish during estivation. AB - Thyrotropin-releasing hormone (TRH) has been implicated as an important modulator of arousal state in mammals. Changes in the content of TRH in several brain regions accompany hibernation in the ground squirrel. In the present study, the involvement of TRH in the regulation of arousal was further investigated in the African lungfish, Protopterus annectens, which contain high concentrations of TRH throughout its central nervous system and enter a hibernation-like state, estivation. Lungfish were divided into three groups. Group 1 was fed normally, group 2 was starved while aquatic, and group 3 was allowed to enter into a state of estivation. After 3 months, the lungfish were sacrificed and the concentrations of TRH, norepinephrine, dopamine, and serotonin were determined in the telencephalon, diencephalon, medulla, and spinal cord. In estivation, there was a significant decline in the concentration of TRH in the diencephalon, with no alteration in other regions. Starvation had no effect on regional TRH concentrations. The concentration of norepinephrine, dopamine, and serotonin did not change in estivation; however, a significant elevation of norepinephrine in the diencephalon and dopamine in the telencephalon was observed in starvation. Starvation and estivation were associated with significant declines in the protein content of the diencephalon and medulla. The estivation-linked decline in TRH in the diencephalon of the lungfish is similar to the decrease in TRH content in the hypothalamus in hibernating ground squirrels. These findings lend further support to the importance of TRH in the regulation of arousal state. PMID- 2110920 TI - rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster. AB - rhomboid (rho) belongs to a group of four genes involved in the elaboration of positional information at a ventrolateral level in the Drosophila embryo. Mutations at any of these four loci also lead to a variety of other phenotypes, including reduction in the number of stretch receptor organs (chordotonal organs) in the peripheral nervous system (PNS). We have cloned rho with the aid of a lacZ bearing P-element inserted into the rho gene. In the early blastoderm stage, a putative rho transcript is expressed in ventrolateral strips corresponding to the domain of activity of the rho gene on the embryonic fate map. Later expression of the transcript correlates with regions of the embryo that are disrupted in rho mutants and includes a cell that may be the precursor for the missing stretch receptor organs. We hypothesize that rho acts very early in differentiation pathways to specify the identities of domains and isolated precursor cells. Sequence analysis suggests that this transcript codes for a trans-membrane protein. PMID- 2110921 TI - The E75 ecdysone-inducible gene responsible for the 75B early puff in Drosophila encodes two new members of the steroid receptor superfamily. AB - A pulse of the steroid hormone ecdysone at the end of Drosophila larval development triggers coordinate changes in both larval and imaginal tissues that result in metamorphosis to the adult fly. In larval salivary glands, this pulse activates a genetic regulatory hierarchy manifested by the induction of two kinds of transcription puffs in the polytene chromosomes: a small set of "early" puffs representing a primary response to the hormone, and a complex set of "late" puffs whose delayed appearance is dependent on proteins synthesized during the primary response. We isolated a 50-kb ecdysone-inducible gene, E75, that occupies the early puff locus at 75B. E75 contains two overlapping transcription units. The E75 A unit is a coextensive with the E75 gene and contains six exons: two 5' proximal exons, A0 and A1, which are specific to this unit, and exons 2-5, which are common to both units. The E75 B unit is 20 kb long and contains five exons, a 5'-terminal exon, B1, located within the second intron of E75 A, and the common exons 2-5. Large open reading frames start within the first exon of each unit and continue into the last exon and therefore encode two different proteins. Both proteins exhibit sequence similarity to the conserved DNA-binding and hormone binding domains of proteins in the steroid receptor superfamily. The two putative zinc fingers that characterize the DNA-binding domain are encoded by exon A1 and exon 2, so that the E75 A protein contains both fingers, whereas the E75 B protein contains only the second. Both proteins contain the same putative hormone binding domain encoded by exon 4. PMID- 2110922 TI - The inner core of the serum response element mediates both the rapid induction and subsequent repression of c-fos transcription following serum stimulation. AB - Serum stimulation of quiescent fibroblasts results in a dramatic increase in c fos transcription that peaks by 15 min and is then rapidly repressed to basal levels within 60 min. Using a nuclear run-on assay to follow directly the kinetics of transcription of mutant c-fos constructs, we demonstrate that the serum response element (SRE) is the site of regulation of both the induction and repression events. This is indicated by the ability of the SRE to mediate c-fos kinetics of induced transcription when fused to a heterologous gene and in the absence of a recognizable TATA element. Functions of the inner core and the outer palindromic arms of the SRE have been determined by mutagenesis. The 14-bp inner core binds the serum response factor (SRF) and is, itself, sufficient to mediate both the induction and shutoff of serum-stimulated transcription. Therefore, SRF and any other factors that regulate the transient kinetics of c-fos transcription require no more than these 14 nucleotides to function. The palindromic outer arms of the SRE stabilize the binding of SRF and thereby enhance the transcriptional response to serum. Autoregulation by the c-fos gene product is not affected by the direct interaction of Fos/Jun complexes with the c-fos promoter and is likely to be mediated by either a novel function of the Fos protein or by an effect of Fos on the expression of another gene. PMID- 2110923 TI - Spatial and temporal control elements of the Drosophila engrailed gene. AB - engrailed (en) is a segmentation gene expressed in a series of stripes throughout embryonic development. Here, I show that regulatory sequences for striped expression are present within the first intron of en. The 1-kb intron is able to confer striped expression early, but not late, in development. This shows that different regulatory sequences are required for en stripes at different times in development. Furthermore, stripes generated by the intron are coincident with en stripes in a wild-type background but behave differently from endogenous engrailed stripes in some segmentation mutant backgrounds. Thus, although the intron can induce apparently normal stripes, it lacks some of the regulatory sequences present within the endogenous gene. These experiments suggest that multiple regulatory programs control an expression in stripes, and each may be able to confer "normal" spatial regulation independently. PMID- 2110924 TI - DNA single strand breakage by H2O2 and ferric or cupric ions: its modulation by histidine. AB - The role of histidine on DNA breakage induced by hydrogen peroxide (H2O2) and ferric ions or by H2O2 and cupric ions was studied on purified DNA. L-histidine slightly reduced DNA breakage by H2O2 and Fe3+ but greatly inhibited DNA breakage by H2O2 and Cu2+. However, only when histidine was present, the addition of EDTA to H2O2 and Fe3+ exhibited a bimodal dose response curve depending on the chelator metal ratio. The enhancing effect of histidine on the rate of DNA degradation by H2O2 was maximal at a chelator metal ratio between 0.2 and 0.5, and was specific for iron. When D-histidine replaced L-histidine, the same pattern of EDTA dose response curve was observed. Superoxide dismutase greatly inhibited the rate of DNA degradation induced by H2O2, Fe3+, EDTA and L-histidine involving the superoxide radical. These studies suggest that the enhancing effect of histidine on the rate of DNA degradation by H2O2 and Fe3+ is mediated by an oxidant which could be a ferrous-dioxygen-ferric chelate complex or a chelate ferryl ion. PMID- 2110925 TI - Schistosomal colonic disease. AB - This study evaluates 216 patients with schistosomal colonic disease, diagnosed by endoscopic biopsies at the Armed Forces Hospital, Riyadh. The colonoscopic appearance was suggestive of schistosomiasis in 98 of these patients (45.37%), Schistosoma mansoni ova in stool was detected in only 24 of these 216 patients (11.11%). The most common histopathological finding in colonic biopsies of these patients was Schistosoma mansoni ova in the colonic mucosa with no or mild inflammatory cells infiltrates. These findings correlate with the endoscopic appearances in most patients. The most common symptoms were abdominal pain or distention in 84 patients (38.88%). Sixty five patients (30.09%) had hepatosplenic schistosomiasis. Eight patients had schistosomal polyps and two patients had colonic malignancy in which no association between their malignancy and Schistosoma mansoni infection was established. After antischistosomal treatment follow up, sigmoidoscopy was normal in 28 patients who previously had abnormal endoscopic appearances. Colonoscopic examination is valuable in colonic schistosomiasis as it can show characteristic colonic lesions and colonic biopsies are diagnostic and correlates with histological findings. PMID- 2110926 TI - Gastroenterologists and nutritional support. PMID- 2110927 TI - EDTA-induced platelet aggregation can be avoided by a new anticoagulant also suitable for automated complete blood count. AB - In vitro EDTA-induced platelet aggregation is a fairly rare event but can have serious clinical consequences producing pseudothrombocytopenia and pseudoleukocytosis. Sixteen specimens with previously recognized EDTA-induced platelet aggregation were collected in a new anticoagulant-antiaggregant mixture containing trisodium citrate 17 mmol/l, pyridoxal 5'-phosphate 11.3 mmol/l and Tris 24.76 mmol/l (CPT mixture) and analyzed at various times after venepuncture with four hematological instruments: Coulter Counter S-Plus STKR, Technicon H6000, Technicon H1 and Ortho ELT-8. In CPT-anticoagulated specimens the signals and instrumental flags of platelet clumping were absent, and the platelet number correlated very well with a microscopic count from a finger stick drawn into Unopette. The complete blood count was very similar in "normal" hematological specimens either collected in K3. EDTA or in CPT, although Technicon H1 and Ortho3 ELT-8 required a suitable calibration for MCV and hematocrit in the latter mixture. Mean platelet volume was stable for up to 24 h only in CPT-collected specimens, if it was measured on a Coulter Counter S-Plus STKR. In routine hematological practice CPT can be an alternative anticoagulant to K3. EDTA, most suitable for automated complete blood count and useful in avoiding EDTA-induced platelet clumping. PMID- 2110928 TI - Familial occurrence of multiple myeloma and monoclonal gammopathy of undetermined significance in 5 siblings. AB - The etiology of monoclonal gammopathies remains unclear but familial occurrence of immunopathies seems to favor a possible hereditary background. In support of this view we report on a family in which five siblings had a monoclonal gammopathy. When MGUS was diagnosed in two of them, a family study was carried out: one sister died from multiple myeloma and four out of the seven living siblings were discovered to have a MGUS. The immunogenetic study (HLA) showed no direct correlation between haplotypes and the presence of the monoclonal protein. Nevertheless possible environmental exposure to viruses, chemicals and radiation was apparently excluded. This new report on familial involvement, the second ever reported for number of affected subjects, strongly supports the theory of genetic predisposition in the development of plasma cell dyscrasias. PMID- 2110929 TI - Nodal and extranodal lymphoproliferative disorders in Sjogren's syndrome: a clinical and immunopathologic study. AB - Sjogren's syndrome (SS) is frequently associated with both reactive and neoplastic lymphoproliferative disease. Over a 12-year period beginning in 1970, 21 of 138 patients with SS followed at two tertiary university medical centers had biopsies taken of enlarged lymph nodes (18) or extranodal lymphoid infiltrates (8). Many had immunologic studies performed on fresh tissue and all had paraffin-embedded tissue available for histochemical and immunoperoxidase studies. Eight of our patients had malignant lymphomas which were chiefly B cell neoplasms including two lymphoplasmacytic lymphomas and two follicular center cell lymphomas. The remaining 13 patients had either reactive adenitis (usually with follicular hyperplasia) or atypical lymphoid hyperplasia which failed to meet both histopathologic and immunopathologic criteria for malignancy. None of the nine patients with reactive hyperplasia has yet progressed to lymphoma, while one of four patients with atypical lymphoid hyperplasia progressed to overt lymphoma. Clinical features such as age, duration of disease, extent of lymphadenopathy, splenomegaly, or parotid swelling failed to identify those subsets of patients with lymphadenopathy at increased risk for lymphoma. Recognition of lymphoma in two patients was greatly facilitated by tissue immunologic studies demonstrating focal areas of monotypic B cell proliferation. In one patient in whom the histopathologic diagnosis was immunoblastic sarcoma of B cells, tumor cells were L26-negative and strongly UCHL1-positive suggesting T cell differentiation. In three patients with relatively homogeneous extranodal lymphoid infiltrates, B cell polyclonality on tissue immunoperoxidase studies, and the absence of cytologic atypia, precluded a diagnosis of malignant lymphoma; none of these three patients has progressed to overt lymphoma. Our results indicate that (1) patients with SS develop a variety of B cell lymphomas and other lymphoproliferative disorders, and (2) the nature of the lymphoproliferative disorder is best determined by multiparameter analysis including immunologic phenotyping. PMID- 2110930 TI - Cocultivation of Fanconi anemia cells and of mouse lymphoma mutants leads to interspecies complementation of chromosomal hypersensitivity to DNA cross-linking agents. AB - We have studied the effects of cocultivation on the frequency of mitomycin C (MMC)-induced chromosomal aberrations. This was carried out by cocultivating Fanconi anemia (FA) cells from the genetic complementation groups A and B with both normal mouse lymphoma L5178Y cells and the derived "FA-like" mutant cells, MCN-151 and MCE-50, assigned to complementation groups I and II, respectively. The results show a partial complementation of the defect (i.e. a reduction in the frequency of chromosomal aberration) in FA group A cells cocultured with normal or group II mouse cells, and a partial correction of mouse group I cells cocultived with normal or FA group B human cells. No reciprocal effects were observed between FA group A cells and mouse group I mutant cells; the frequencies of MMC-induced chromosomal aberrations in these cells remained unchanged by cocultivation. Moreover, no complementation was observed for both FA group B cells and mouse group II cells, after cocultivation with normal cells of either mouse or human origin. This implies that a diffusible factor released by normal human and mouse cells, and by FA group B and mouse group II mutant cells, can correct at least in part the chromosomal defect of FA group A and mouse group I mutant cells. With normal human or mouse cells, the frequency of chromosomal breakage after cocultivation remains the same as that observed in non-cocultived cells. This suggests that no detectable clastogenic factor is released by human FA or "FA-like" mouse cells. PMID- 2110931 TI - WEHI 164 subclone 13 assay for TNF: sensitivity, specificity, and reliability. AB - Tumor necrosis factor alpha (TNF) is a peptide monokine involved in a number of immune reactions. To further understand the role of TNF in disease states it is critical to have an inexpensive, yet sensitive and specific assay. Additionally, the effects of prostaglandin E2 (PGE2), dexamethasone (dex), and cyclosporine A (CsA) on TNF gene expression have been studied, although little is known of the effects these compounds have on TNF containing samples. The aim of this study is to determine the sensitivity and specificity of a highly sensitive cell line to the actions of TNF, and to elucidate parameters which affect the stability of TNF in biological fluids. Dex and PGE2 at concentrations of 10(-5), 10(-7), and 10( 9) M, were shown not to effect the WEHI assay, and neither did CsA (10 ng/ml-1 ug/ml). The cells were not lysed by recombinant murine IL-1 alpha or beta, human recombinant IL-1 alpha or beta, human recombinant IL-2 or human recombinant IL-6 at concentrations ranging from 0.02 pg/ml to 1.0 ug/ml, or murine gamma-IFN from 100 pg/ml to 10 ng/ml. TNF containing samples with 1%-10% fetal calf serum maintained their cytolytic activity even after three freeze-thaw cycles. Serum samples did not lose any cytolytic activity with up to 11 cycles of freezing and thawing whereas, tissue culture media, containing TNF, lost significant activity with freeze-thawing. The WEHI assay has successfully detected cytolytic activity from lipopolysaccharide stimulated specimens from a number of different species. These data show the utility of this highly sensitive and specific assay. Furthermore, the WEHI assay showed a high degree of reproducibility in repeated assays. PMID- 2110932 TI - [Significance of vitamins in parenteral nutrition]. AB - Parenteral nutrition is incomplete without vitamins. Marginal vitamin deficiency under parenteral nutrition is certainly more common than generally recognized. Even marginal and undiscernable vitamin deficiency interferes with healing processes and increases the rate of complications since vitamins are involved in a variety of ways in wound healing, regeneration processes and immune function. If total parenteral nutrition is necessary for longer periods of time, exceeding 5 days, vitamins should be substituted in the recommended doses. The assessment of a marginal vitamin deficiency is difficult to perform and extremely expensive. It is therefore easier, safer and cheaper to substitute vitamins in total parenteral nutrition from the beginning, if preceeding malnutrition is likely. Recommendations for dosage and mode of application are reported and explained. PMID- 2110933 TI - The influence of posttraumatic parenteral calorie and nitrogen supply upon the cumulative nitrogen balance. AB - The aim of the study was to describe the influence of posttraumatic calorie and nitrogen (N) supply upon the cumulative N-balance by analyzing the literature of the past 18 years. Three groups of patients were formed, in which nutritional therapy was performed following trauma of differing severity: (1) patients following moderate trauma-N-losses 10-15 g/day; (2) patients following severe trauma--N-losses 15-20 g/day; and (3) polytraumatised patients--N-losses more than 20 g/day. The data gained for the calorie and N-supplies as well as for the N-balances in each group of patients served as a basis for the calculation of regression analyses of higher order; in these the cumulative N-balance was regarded as a function of the calorie and the N-supply: NBcum = f (C, N) Whilst for the group of polytraumatized patients only statements for a nutrient supply of about 20-30 kcal/kg BW/day and 0.2-0.3 g N/kg BW/day are possible, due to the limited data available, general statements about the different influence of calorie and N-supply can be made for nutritional therapy after moderate and major trauma; the calculated functions reveal that the N-supply influences the N balance decisively, whereas the calorie supply exerts only a slight N-sparing effect. The mathematically calculated optimum of the N-supply after severe trauma is 0.2 g/kg BW/day, corresponding to an amino acid supply of 1.25 g/kg BW/day. PMID- 2110934 TI - [A new amino acid solution for parenteral nutrition of premature infants, newborn infants and infants]. AB - A new amino acid solution (Aminopad 5% and Aminopad 10%) was used for intravenous feeding of 240 preterm and term newborn infants in 4 hospitals. Indications, dosages and infusion sites were up to the policies of the 4 hospitals. Plasma amino acid concentrations were measured in 491 samples which were obtained during steady 24 h infusions of the daily doses. Results were analyzed in four subgroups formed according to the postmenstrual ages of the patients at the time of blood withdrawal and showed good agreement with the reference values. Acute cholestasis was observed in 22 infants which could be explained by bacterial infection alone in 18 patients. PMID- 2110936 TI - [Abstracts of the 9th combined annual meeting of the Austrian Society for Clinical Nutrition and the German Society for Artificial Nutrition. Vienna, 28-31 March 1990]. PMID- 2110935 TI - [Energy requirements of surgically treated, injured and infected patients]. AB - There is always a distinct increase in energy expenditure in postoperative, posttraumatic and septic patients. In order to predict this increase in energy expenditure an enormous number of formulas have been developed. However, the problem with all these formulas is that they cannot sufficiently take into account the peculiarities of the underlying disease, the general and nutritional condition or the varying influence of the phase of disease. Furthermore, all these patients continuously show a considerable change in body weight which can be attributed to a shifting of the water balance. In all of these cases any calculation of energy expenditure based on body weight will inevitably be incorrect. Therefore, it is recommended that predicting formulas only be used as orienting guidelines in all uncomplicated postoperative or posttraumatic courses. In patients with multiple injuries or septic complications the real energy expenditure should be measured by indirect calorimetry in order to adapt energy intake during enteral or parenteral nutrition to the very different metabolic situations. PMID- 2110937 TI - Effects of a gel forming dietary fiber, guar gum, on the absorption of glibenclamide and metabolic control and serum lipids in patients with non-insulin dependent (type 2) diabetes. AB - Nine patients with non-insulin-dependent diabetes (NIDDM) treated with glibenclamide (3.5 mg b.i.d.) participated in this randomized double-blind placebo controlled crossover study to evaluate the effects of granulated guar gum (5 g t.i.d. with meals) on the absorption of glibenclamide and metabolic control and serum lipids. Each treatment period lasted for 4 weeks, and there was a wash out period of one week between the treatments. The fasting blood glucose (10.5 +/ 3.4 mmol/l on guar gum vs 11.3 +/- 3.7 mmol/l on placebo, p less than 0.05) and serum total cholesterol (5.9 +/- 1.4 mmol/l on guar gum vs 6.6 +/- 1.6 mmol/l on placebo; p less than 0.05) levels were lower after the treatment with guar gum than placebo. No significant differences were observed in serum triglycerides or HDL cholesterol between guar gum and placebo treatments. The administration of guar gum together with glibenclamide did not change significantly the maximum concentration (223 +/- 196 ng/ml on guar gum vs 184 +/- 138 ng/ml on placebo; n = 7, NS) or area under the curve (AUC0-6) [729 +/- 813 (ng/ml) X h on guar gum vs 560 +/- 513 (ng/ml) X h on placebo; NS] of glibenclamide. The fasting serum glibenclamide concentrations were similar at the end of the 4-week treatment period with guar gum and placebo. In conclusion, guar gum improved the metabolic control and decreased serum lipids of patients with NIDDM. In addition, guar gum ingested with glibenclamide did not interfere with the absorption of glibenclamide. PMID- 2110938 TI - The accumulation of five quinolone antibacterial agents by Escherichia coli. AB - The accumulation of five radiolabelled quinolone antibacterial agents by Escherichia coli KL16 was examined using a vacuum filtration method. Preliminary experiments were performed to determine the optimum quinolone concentration, inoculum of cells, filter washing regimen and filter type. All five quinolones showed a similar biphasic pattern of accumulation with high radioactive counts cell-associated during the first ten seconds of the assay, followed by steadily increasing accumulation over 30 min. Analysis of the mean accumulation after 30 min for each quinolone showed that there was no direct relationship between quinolone accumulation and antibacterial activity (as quantified by the MIC or bactericidal activity). Mechanistic investigations showed that accumulation was decreased by low reaction temperatures, acid pH and the presence of the metabolic inhibitors 2,4-dinitrophenol, potassium cyanide and sodium azide. These results suggest that quinolone accumulation by E. coli KL16 is partly dependent on cell metabolism and may proceed by an active transport mechanism. Treatment of cells with EDTA was found not to increase quinolone accumulation, suggesting that the outer membrane of E. coli KL16 does not act as a permeability barrier to these quinolones. The implication of these results in terms of possible mechanisms of bacterial resistance to quinolones is discussed. PMID- 2110939 TI - The effect of ofloxacin on the immune system of elderly patients. AB - In twenty elderly patients with infectious diseases, some immune parameters were evaluated before and after treatment with ofloxacin. Results showed that the number of T cells, B cells, gamma-Interferon plasma concentrations and serum immunoglobulin levels were not affected following ten days treatment (600 mg/per day). These data suggest that this antibiotic does not affect the immune parameters studied. However, inhibition of other immune functions cannot be excluded. PMID- 2110940 TI - Phenoxymethyl-penicillin vs co-amoxyclav in acute recurrent tonsillitis. PMID- 2110942 TI - Failure of BCAA supplementation to promote nitrogen retention in injured patients. AB - The purpose of this study was to determine if supplementing total parenteral nutrition (TPN) with lipids or the branched chain amino acids (BCAA) leucine, isoleucine, and valine influences nitrogen balance in the injured patient. Four TPN study solutions were used, with each patient receiving two of the solutions for 4 days each. Group A received solutions consisting of 19% and 44% BCAA, with nonnitrogen calories supplied by 100% carbohydrate. Group B received a 7:3 carbohydrate-to-lipid ratio of nonnitrogen calories as a fuel source. Neither BCAA supplementation nor varying fuel substrates promoted a difference in nitrogen retention. The added cost of BCAA supplementation, along with the lack of an effect upon nitrogen accretion, indicates that greater benefits must be demonstrated before widespread use of BCAA supplementation can be recommended in the injured patient. PMID- 2110941 TI - The effect of a single whole-blood transfusion on cytokine secretion. AB - The effect of a single whole-blood transfusion on the cascade of cytokine secretion was studied in patients with chronic renal failure. The results indicate that 1 week after blood transfusion, no significant changes were observed in the secretion of interleukin-2, colony-stimulating factor, tumor necrosis factor, and gamma-interferon. However, 2 weeks after blood transfusion, a sharp decrease was observed in the generation of these cytokines. A decrease of about 70% was observed in interleukin-2, tumor necrosis factor, and gamma interferon secretion. The production of colony-stimulating factor 2 weeks after blood transfusion amounted to about 30% less than baseline levels. No statistical differences in interleukin-1 production were observed throughout the study. In addition, we found that the decrease in cytokine secretion was paralleled by a sharp increase in the in vitro secretion of prostaglandin E2. Thus the beneficial effect of blood transfusion on graft survival might be due in part to an immunosuppressive effect brought about by immunoregulatory changes via the cascade of cytokine secretion. PMID- 2110943 TI - Effect of a single oral dose of ascorbic acid on body temperature and trace mineral fluxes in healthy men and women. AB - Several metabolic changes characteristic of the acute-phase response were examined in healthy men and women following a single 1 g dose of ascorbic acid. Utilizing a placebo-controlled, double-blind protocol, oral body temperatures were recorded in rested, fasted subjects (0900 hr) prior to the consumption of 1 g L-ascorbic acid or placebo (n = 10/group). Temperatures were recorded hourly for the next 8 hours, and again the next morning in the rested, fasted state (0900 hr). Blood samples, collected at 0, 4, and 24 hours post-dose, were analyzed for plasma ascorbate, iron, and zinc. Mean oral body temperature was significantly elevated 2 hours post-dose in the experimental subjects compared to controls (+0.7 degrees F, p = 0.03). In the vitamin-dosed subjects, mean plasma ascorbate rose 32% over the control value after 4 hours (1.11 +/- 0.08 and 0.84 +/- 0.06 mg/100 ml, ns). Serum iron levels were similar in the two groups at 0 and 4 hours post-dose, but at 24 hours post-dose mean serum iron of the vitamin dosed subjects fell to 73% of that recorded for the control subjects (77 +/- 8 and 105 +/- 10 micrograms/100 ml, p = 0.04). Plasma zinc levels were similar for both groups at 0, 4, and 24 hours post-dose. These data indicate that ascorbate administration, at a level commonly supplemented in the US diet, elicits several host metabolic responses similar to those observed following exposure to infectious or inflammatory agents. These metabolic changes are most likely due to the reducing potential of the vitamin and may factor in the reported prophylactic success of vitamin C supplementation. PMID- 2110944 TI - Effects of praziquantel and oxamniquine on a Saudi Arabian strain of Schistosoma mansoni in mice. AB - The prophylactic and curative effects of praziquantel and oxamniquine on a Saudi Arabian strain of Schistosoma mansoni in MF-1 mice were assessed. The drugs were administered orally. At 240 mg/kg praziquantel, there was a reduction of 89.1% in adult worm recovery and a marked reduction in tissue deposited eggs. The reduction in adult worm recovery after dosing with 50 mg/kg oxamniquine was 89.2%. At low doses (40 mg/kg praziquantel and 30 mg/kg oxamniquine) administered at 11 days, 5 days and 3 h before and 5, 21 and 49 days after infection, the reduction in adult worm recovery was 0.0%, 65.1%, 58.8%, 33.6%, 0.0% and 76.0% for praziquantel and 0.0%, 66.0%, 60.0%, 41.3%, 10.8% and 79.0% for oxamniquine. Numbers of lung schistosomula and the size of hepatic granulomata were also reduced. PMID- 2110945 TI - Influence of intramolluscan larval stages of Echinostoma liei on the infectivity of Schistosoma mansoni cercariae. AB - During co-infection of Biomphalaria glabrata with Schistosoma mansoni and Echinostoma liei, S. mansoni cercariae released before the complete resorption of S. mansoni sporocysts show a very strong decrease of their infectivity in mice. Under conditions of high interspecific competition (i.e. when the snails are infected by E. liei 8 days after infection by S. mansoni), the mean overall worm return is five times lower than that of the control experiment. A marked decrease of the infectivity of cercariae is also noted when snails, infected exclusively with either sporocysts of S. mansoni or rediae of E. liei, are associated in the same tank. PMID- 2110946 TI - Mean cell volume of human blood leucocytes and resident and activated murine macrophages. AB - The mean cell volume (MCV) of human blood leucocytes and resident and activated murine macrophages was measured with a Coulter counter connected to a 256 channelyzer. The values found for human blood monocytes, granulocytes, and lymphocytes were 421 +/- 24 femtolitre (fl), 334 +/- 32 fl, and 204 +/- 19 fl, respectively. Resident murine peritoneal macrophages were significantly smaller than rIFN-gamma-activated and BCG/PPD-activated peritoneal macrophages and resident alveolar macrophages. PMID- 2110947 TI - Comparison of two serum bactericidal assays for Neisseria gonorrhoeae. AB - Pooled normal human serum killing of 14 strains of Neisseria gonorrhoeae was assessed by dilution plate and microtiter methods. In both assays, the strains presented a spectrum of sensitivity to the serum. In the dilution plate assay, results with two different concentrations of human serum were similar for most, but not all of the strains tested. When data for all of the strains were compared, no correlation was found between the dilution plate and microtiter bactericidal assays. Finally, we found that the bactericidal capacities of intact and complement-depleted human sera were very similar when assessed by microtiter methods, suggesting a non-complement-mediated serum killing mechanism. PMID- 2110948 TI - Optimal fixation of cells for use in solid-phase ELISA. AB - Glutaraldehyde (GA) is commonly used to achieve the stable fixation of whole cells onto microtitre plates for use in solid-phase ELISA. Concentrations of GA greater than 0.10% (v/v) were found to result in increased levels of non-specific binding of antibodies in ELISA. However, the use of 0.05-0.025% (v/v) GA permitted the stable fixation of cells whilst minimizing the non-specific effects seen with higher GA concentrations. The binding of cells onto microtitre plates was also found to be highly variable depending on both the type of plates and the nature of the cells being used. PMID- 2110949 TI - Immunological detection of mycobacterial antigens in infected fluids, cells and tissues by latex agglutination. Animal model and clinical application. AB - We devised an immunoassay for the detection of mycobacterial antigens in cell lysates and in tissue extracts which is based on the agglutination of latex particles coated with anti-Mycobacterium bovis F(ab')2, followed by counting of non-agglutinated particles. Mycobacterium bovis cell lysates were tested and a reference curve was established, having a lower limit of detection of 15-20 Mycobacteria. We were able to detect mycobacterial antigens in cell lysates from bronchoalveolar washings and in spleen and liver lysates obtained from experimentally infected rabbits. Antigens were also detected in ten out of 11 samples obtained from patients with proven tuberculous infection. These samples were readily distinguished from 32 negative control samples after pepsin treatment. In contrast, periodate treatment of samples to destroy carbohydrate, abolished all reactivity. Following gel filtration chromatography we identified three peaks with antigenic properties in samples of all types. The detection of mycobacterial carbohydrate antigens by latex agglutination and particle counting should be a useful adjunct in the diagnosis of tuberculosis. PMID- 2110950 TI - International orientation: a must? PMID- 2110951 TI - Arnhem consensus on preprosthetic surgery, May 1989. PMID- 2110952 TI - Soft tissue profile changes after mandibular vestibuloplasty. A two-year follow up study comparing the Edlan flap, mucosal and skin graft methods. AB - It is the aim of the present study to examine the pattern of postoperative changes in the soft tissue profile of 50 edentulous patients after 3 common types of mandibular vestibuloplasty, the Edlan flap operation (n = 15), the buccal mucosal graft (n = 19), and the skin graft vestibuloplasty (n = 16). The soft tissue profile changes were recorded on lateral cephalometric radiographs taken preoperatively, and after 1, 3, 6, 12, and 24 months post surgery. The 3 groups did not differ with respect to clinical features or presurgical cranio-facial morphology. Neither was any significant difference in postoperative profile changes found between the groups. The surgery gave rise, directly and indirectly, to a number of changes in the facial soft tissue profile many of which were interrelated. The chin thickness increased by 2.3 mm, and the lower lip height exhibited a reduction of 1.8 mm at 1 month after surgery as a direct consequence of the operation. After 3 months the profile changes were mostly associated with the reduction of the anterior face height (overclosure). PMID- 2110953 TI - Somatosensory evoked potential assessment of the inferior alveolar nerve following third molar extraction. AB - Injury to the inferior alveolar nerve can occur during 3rd molar removal. In this study, 14 patients who had 3rd molars removed were evaluated by 4 methods: 1) threshold to electrical stimulation, 2) visual analogue scale subjective ratings of electrical stimulation, 3) two-point discrimination in mental nerve area, and 4) analysis of somatosensory evoked potentials. The last technique proved to be the most sensitive of the methods, providing an objective evaluation as compared to other methods which require a subjective interpretation by the patient. PMID- 2110954 TI - Paradoxical reactions to rectal midazolam as premedication in children. AB - Eighty healthy children, between the ages of 2 and 7 years, who were to undergo oral surgical procedures under general anaesthesia, were allocated randomly to 4 groups. Three groups received rectal midazolam, and the other group a placebo (saline) as premedication 30 min prior to induction of anaesthesia. Group A children received midazolam 0.25 mg/kg, Group B 0.35 mg/kg and Group C 0.45 mg/kg. No statistically significant difference was found between the treatment groups as to the effect on systolic- (p = 0.6920) and diastolic (p = 0.8701) blood pressures, respiration (p = 0.0505) and pulse (p = 0.6192) rates at either pre- or post-sedation levels. However, the results indicate that levels of anxiolysis and sedation were significantly associated with midazolam dosage (p less than 0.0001). PMID- 2110955 TI - Management of malunited mandibular condylar fractures. AB - The non-surgical treatment of mandibular condylar fractures, may occasionally result in articular imbalance and temporomandibular joint dysfunction. This may be attributed to condylar head displacement and resorption, resulting in a shortened vertical ramus and lost posterior vertical facial height. Restoring the vertical ramus height is essential in the treatment of such dysfunction, and may be accomplished by unilateral, or bilateral ramus osteotomies. Four examples of patients treated with mandibular ramus osteotomies to restore vertical ramus height, with subsequent improvement in occlusal balance and function are presented. The use of the sagittal split mandibular osteotomy and the external vertical ramus osteotomy, stabilized with small osseous plates, and monocortical screws, is discussed. PMID- 2110956 TI - Syndromology: an updated conceptual overview. VII. Aspects of teratogenesis. AB - Principles of teratogenesis are reviewed, including adverse environmental factors and the genotype, timing of exposure, mechanisms and pathogenesis, the nature of teratogenic agents, manifestations of deviant development, and dosage. Human teratogenic conditions are summarized with special emphasis on the fetal alcohol syndrome, fetal hydantoin syndrome, fetal trimethadione syndrome, fetal valproate syndrome, warfarin embryopathy, retinoic acid embryopathy, congenital rubella syndrome, radiation effects, and diabetic embryopathy. PMID- 2110957 TI - Syndromology: an updated conceptual overview. VIII. Deformations and disruptions. AB - A deformation is an abnormal form or position of the body caused by nondisruptive mechanical forces. Clubfoot, congenital hip dislocation, and infantile mandibular asymmetry (not based on mandibular malformation) serve as examples. The musculoskeletal system is involved in almost all deformations. Various disturbances of intrauterine movement are the usual causes and commonly occur during the fetal period. Causes may be mechanical or malformational. The former includes first pregnancies, small maternal size, uterine malformations and tumors, and amnionic rupture leading to oligohydramnios. Malformational causes usually involve the urogenital system and the central nervous system. A disruption is a morphologic defect of an organ, part of an organ, or a larger region of the body resulting from a breakdown of, or interference with, an originally normal developmental process. Amnionic band disruptions with digital amputations serve as an example. The most recent studies of disruptions and their suggested mechanisms are discussed. Finally, the interrelationships between malformations, deformations, and disruptions are explained. PMID- 2110958 TI - Fatty change in the human temporomandibular joint disc. Light and electron microscopy study. AB - Joint pain has been associated with fatty infiltration of the knee articulation. The purpose of this study is to report on the histopathological findings, especially fatty changes, that are seen in surgical specimens from the temporomandibular joints (TMJ) of patients that had persistent pain after non surgical therapy. Forty plicated TMJ retrodiscal samples from 25 patients were used in this study. The patients were previously treated with splints for variable periods but not less than 2 months. The specimens were obtained by 2 surgeons using standard TMJ plication techniques. Control disc specimens were obtained from normal appearing cadaveric TM joints. Samples were immediately immersed in glutaraldehyde and processed for light and electron microscopic examination. The specimens were composed mainly of moderately dense tissue with cells that appeared fibroblastic and intermittent chondrocytic type cells. Fatty change, exclusively in association with the perivascular areas, was observed in 27 of 40 specimens. Electron microscopy showed fibroblasts, as well as large fat inclusions adjacent to elastin macroglobules. Fatty infiltration of the TMJ has been interpreted as a degenerative change. It is postulated that kinins and prostaglandins generated in the fat pads can pass freely in tissue fluid to adjacent, highly innervated structures thus leading to joint pain. It is further postulated that the finding of associated elastin with fatty deposition is similar to the atherosclerotic changes encountered in large blood vessels and the aorta. PMID- 2110959 TI - An aid to the selection of chemotherapy regimens for oral cavity carcinomas. Early results of a study of 5-year survival based on antioncogram selection of anti-cancer drugs. AB - The antioncogram is an aid to the selection of cytostatic drugs in the treatment of oral cavity carcinomas. In comparison with drug selection based on clinical experience, the antioncogram-oriented choice of the most promising drug in vitro results in improved survival rates. PMID- 2110960 TI - Pretapped and self-tapping screws in the human midface. Torque measurements and bone screw interface. AB - Better contact between AO miniscrews and the bone and greater resistance against torque are achieved in the human midface if the thread is not pretapped. This was demonstrated by 60 methacrylate fixed human midfacial bone sections and by 100 torque measurements. It is concluded that pretapping is not to be recommended in the thin bone of the midface. PMID- 2110961 TI - 1989 International Association of Oral and Maxillofacial Surgeons Meeting in Jerusalem. PMID- 2110962 TI - Bacterial colonization of the parotid duct in xerostomia. AB - Salivary flow rate and bacterial colonization of the parotid main duct were investigated in 17 patients referred for sialography and in 10 healthy controls. Cultures in the controls were negative whilst the patient group revealed bacterial colonization of the main duct, especially in those with the lowest flow rates. The implications of this finding in patients at high risk of endocarditis who will be undergoing sialography are discussed. PMID- 2110963 TI - [Plasmid profiles of aminoglycoside-resistant Pseudomonas aeruginosa]. AB - Three-hundred and eighty-five strains of Pseudomonas aeruginosa were isolated from Gunma University Hospital from 1984 to 1987. Out of these strains, thirty strains (7.8%) were resistant to GM. We investigated antibiograms, serotyping, phage typing, and plasmid profiles of these strains. The following results were obtained. 1) Only one kind of GM-resistant (GMr) plasmid was obtained in 1984. Two kinds of GMr plasmids were found in 1985, and three kinds of GMr plasmids in 1987, respectively. 2) A strain of I-serotype and Hh8-phage type containing the plasmid I (GM-SM-SA-PIPC, Tra-, 22.6Kb or 22.5 Kb) was suspected to cause the nosocomial infection mainly in Departments of Internal Medicine, and a strain of non-serotypable and Hh8-phage type containing the plasmid IV (GM-SM-SA-CP-Hg, Tra+, IncP-2) was suspected to cause the nosocomial infection mainly in Surgical Departments. 3) Plasmid profiles adding to serotyping and phagetyping contribute to the epidemiological analysis of Pseudomonas aeruginosa infection. PMID- 2110964 TI - Circulating levels of GH-releasing hormone and GH during human pregnancy. AB - To study the potential role of GH-releasing hormone (GHRH) in maintaining circulating levels of GH during pregnancy, 302 maternal plasma samples were collected from non-fasted subjects at various stages of pregnancy and assayed for GHRH using a 'two-site' immunoradiometric assay. The GH and placental lactogen levels were also determined. In addition, maternal plasma samples taken during labour, amniotic fluid and cord blood were also assayed for these hormones. Maternal plasma GHRH levels were similar to non-pregnant levels throughout gestation despite fluctuations in GH values which were always higher than non pregnant levels. There was no significant difference between GHRH levels in maternal plasma and cord blood although high GH levels were observed in the latter. These findings suggest that peripheral GHRH levels do not play an important role in maintaining circulating GH levels during pregnancy. PMID- 2110965 TI - Comparison of the effects of crude and highly purified bovine inhibin (Mr 32,000) on plasma concentrations of FSH and LH in chronically ovariectomized prepubertal heifers. AB - Chronically ovariectomized prepubertal heifers were used for a comparison of the effects of highly purified bovine inhibin (Mr 32,000) and steroid-free bovine follicular fluid (bFF) on the secretion of FSH and LH. In view of the limited availability of highly purified inhibin, an initial study was undertaken to establish the optimal method for administration of bFF inhibin activity. In comparison with the FSH response to a single large i.v. bolus injection of bFF (50 ml; 3250 mg protein), a far more effective suppression of plasma FSH concentrations was achieved when considerably less bFF (6.3 ml; 410 mg protein) was administered gradually over an extended time-period (2 days) either as a continuous i.v. infusion or as a series of 2-hourly i.v. injections. Following a single i.v. bolus injection of bFF, immunoreactive inhibin was cleared rapidly from the circulation (half-life 51 +/- 8 (S.E.M.) min, n = 5), presumably accounting for its limited ability to suppress FSH secretion when administered in this manner. In a second experiment, treatment of ovariectomized heifers (three per group) with highly purified Mr 32,000 bovine inhibin at a dose rate of 15 micrograms/2 h for 2 days significantly (P less than 0.05) suppressed plasma FSH concentrations, which reached their minimum values (40% suppression) during day 2 of treatment. At a lower dose rate (5 micrograms/2 h), inhibin did not significantly affect plasma FSH levels. Administration of bFF was also associated with a dose-dependent suppression of FSH secretion. For each of three dose rates tested (three heifers per group), plasma FSH concentrations were maximally suppressed during day 2 of treatment (65 mg/2 h, 86% suppression, P less than 0.001; 21.7 mg/2 h, 66% suppression, P less than 0.001; 7.2 mg/2 h, 15% suppression, P greater than 0.05). Neither highly purified inhibin nor bFF significantly affected mean plasma LH concentrations, LH pulse frequency or LH pulse amplitude. Thus we have shown for the first time that highly purified Mr 32,000 bovine inhibin does possess in-vivo biological activity in cattle, promoting a selective suppression of plasma FSH concentrations qualitatively similar to that evoked by steroid-free bFF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2110966 TI - Effect of cysteamine on the lysosomal enzymes of the hyperprolactinaemic rat pituitary. AB - The effect of cysteamine on the activity of lysosomal enzymes and the prolactin content of isolated hyperprolactinaemic cells has been investigated. In broken cell preparations, cysteamine markedly stimulated acid prolactin protease activity. In intact cells, however, cysteamine inhibited acid prolactin protease activity and beta-galactosidase. Moreover, the activities of alpha-mannosidase, acid phosphatase, beta-glucuronidase, total arylsulphatase and hexosaminidase were not changed by the addition of cysteamine. Cysteamine significantly depleted the cells of prolactin, and this action was not compromized by the inclusion of either leupeptin, chloroquine or NH4Cl in the incubation media. Taken together, these results indicate that cysteamine does not promote degradation of prolactin and hence depletion of prolactin from the pituitary through a mechanism involving lysosomal enzyme degradation. PMID- 2110967 TI - Mechanical transients of single toad stomach smooth muscle cells. Effects of lowering temperature and extracellular calcium. AB - Smooth muscle's slow, economical contractions may relate to the kinetics of the crossbridge cycle. We characterized the crossbridge cycle in smooth muscle by studying tension recovery in response to a small, rapid length change (i.e., tension transients) in single smooth muscle cells from the toad stomach (Bufo marinus). To confirm that these tension transients reflect crossbridge kinetics, we examined the effect of lowering cell temperature on the tension transient time course. Once this was confirmed, cells were exposed to low extracellular calcium [( Ca2+]o) to determine whether modulation of the cell's shortening velocity by changes in [Ca2+]o reflected the calcium sensitivity of one or more steps in the crossbridge cycle. Single smooth muscle cells were tied between an ultrasensitive force transducer and length displacement device after equilibration in temperature-controlled physiological saline having either a low (0.18 mM) or normal (1.8 mM) calcium concentration. At the peak of isometric force, after electrical stimulation, small, rapid (less than or equal to 1.8% cell length in 3.6 ms) step stretches and releases were imposed. At room temperature (20 degrees C) in normal [Ca2+]o, tension recovery after the length step was described by the sum of two exponentials with rates of 40-90 s-1 for the fast phase and 2-4 s-1 for the slow phase. In normal [Ca2+]o but at low temperature (10 degrees C), the fast tension recovery phase slowed (apparent Q10 = 1.9) for both stretches and releases whereas the slow tension recovery phase for a release was only moderately affected (apparent Q10 = 1.4) while unaffected for a stretch. Dynamic stiffness was determined throughout the time course of the tension transient to help correlate the tension transient phases with specific step(s) in the crossbridge cycle. The dissociation of tension and stiffness, during the fast tension recovery phase after a release, was interpreted as evidence that this recovery phase resulted from both the transition of crossbridges from a low- to high-force producing state as well as a transient detachment of crossbridges. From the temperature studies and dynamic stiffness measurements, the slow tension recovery phase most likely reflects the overall rate of crossbridge cycling. From the tension transient studies, it appears that crossbridges cycle slower and have a longer duty cycle in smooth muscle. In low [Ca2+]o at 20 degrees C, little effect was observed on the form or time course of the tension transients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2110968 TI - Signal transmission through the dark-adapted retina of the toad (Bufo marinus). Gain, convergence, and signal/noise. AB - Responses to light were recorded from rods, horizontal cells, and ganglion cells in dark-adapted toad eyecups. Sensitivity was defined as response amplitude per isomerization per rod for dim flashes covering the excitatory receptive field centers. Both sensitivity and spatial summation were found to increase by one order of magnitude between rods and horizontal cells, and by two orders of magnitude between rods and ganglion cells. Recordings from two hyperpolarizing bipolar cells showed a 20 times response increase between rods and bipolars. At absolute threshold for ganglion cells (Copenhagen, D.R., K. Donner, and T. Reuter. 1987. J. Physiol. 393:667-680) the dim flashes produce 10-50-microV responses in the rods. The cumulative gain exhibited at each subsequent synaptic transfer from the rods to the ganglion cells serves to boost these small amplitude signals to the level required for initiation of action potentials in the ganglion cells. The convergence of rod signals through increasing spatial summation serves to decrease the variation of responses to dim flashes, thereby increasing the signal-to-noise ratio. Thus, at absolute threshold for ganglion cells, the convergence typically increases the maximal signal-to-noise ratio from 0.6 in rods to 4.6 in ganglion cells. PMID- 2110969 TI - Weber and noise adaptation in the retina of the toad Bufo marinus. AB - Responses to flashes and steps of light were recorded intracellularly from rods and horizontal cells, and extracellularly from ganglion cells, in toad eyecups which were either dark adapted or exposed to various levels of background light. The average background intensities needed to depress the dark-adapted flash sensitivity by half in the three cell types, determined under identical conditions, were 0.9 Rh*s-1 (rods), 0.8 Rh*s-1 (horizontal cells), and 0.17 Rh*s 1 (ganglion cells), where Rh* denotes one isomerization per rod. Thus, there is a range (approximately 0.7 log units) of weak backgrounds where the sensitivity (response amplitude/Rh*) of rods is not significantly affected, but where that of ganglion cells (1/threshold) is substantially reduced, which implies that the gain of the transmission from rods to the ganglion cell output is decreased. In this range, the ganglion cell threshold rises approximately as the square root of background intensity (i.e. in proportion to the quantal noise from the background), while the maintained rate of discharge stays constant. The threshold response of the cell will then signal light deviations (from a mean level) of constant statistical significance. We propose that this type of ganglion cell desensitization under dim backgrounds is due to a post-receptoral gain control driven by quantal fluctuations, and term it noise adaptation in contrast to the Weber adaptation (desensitization proportional to the mean background intensity) of rods, horizontal cells, and ganglion cells at higher background intensities. PMID- 2110970 TI - Chronic electroconvulsive seizures down-regulate expression of the immediate early genes c-fos and c-jun in rat cerebral cortex. AB - Acute seizures and other stimuli that increase neuronal activity cause a rapid induction of the immediate-early genes c-fos and c-jun, also referred to as nuclear proto-oncogenes, in the nervous system. In the present study, rats were administered one or more electroconvulsive seizures (ECS) and the responsiveness of c-fos and c-jun to an acute, "test" seizure was examined. Four hours after a single ECS, the induction of c-fos mRNA by a test seizure was blocked, in agreement with earlier findings, but by 18 h the levels of c-fos mRNA could be reinduced by the test seizure, suggesting that 1 day is sufficient to "reset" the responsiveness of this system. However, it was found that chronic, daily ECS treatments resulted in a time-dependent decrease in the expression of c-fos mRNA in response to a test seizure administered 18 h after the last daily ECS; this effect was maximal after 8-10 days of treatment, at which time the induction of c fos mRNA by the test seizure was blocked dramatically. Chronic ECS also blocked the induction of c-jun in response to an acute, test seizure. The effect of chronic ECS on levels of Fos protein was also investigated. It was found that basal levels of Fos protein were reduced after chronic (10 days) ECS and were not induced by a test seizure. Because levels of Fos protein remain elevated 4 h after a single seizure this finding suggests that the mechanisms by which acute (4 h) and chronic (8-10 days) ECS block the induction of c-fos may differ. PMID- 2110971 TI - Developmental expression of Go in neuronal cultures from rat mesencephalon and hypothalamus. AB - The developmental expression of the alpha-subunit of Go was examined in neuronal cultures derived from rat mesencephalon (MES) and hypothalamus (HYP). These cultures were essentially free of contaminating glia and were maintained as a stable population for periods up to 3 weeks. Immunoblotting utilizing specific antisera against Go indicated that in neurons from both brain regions, membrane concentrations of Go increased dramatically during the first 2 weeks in vitro. Thereafter, increases in the amount of Go per neuron kept pace with increasing process (axons and dendrites) formation. Multiple forms of immunoreactive Go were detected in MES and HYP neurons, and the proportions of these forms changed between 4 and 14 days in culture. Finally, increasing neuron density significantly increased membrane levels of Go in MES but not HYP cultures. PMID- 2110972 TI - Use of IFN-gamma in patients with AIDS. AB - The tolerance and toxicity of interferon-gamma (IFN-gamma) was assessed in a phase I/II study of 21 patients with acquired immune deficiency syndrome (AIDS). A highly purified preparation of human recombinant E. coli-produced IFN-gamma was given i.v. twice weekly for an 8 week period. Patients were enrolled in the study in groups of four or five; the initial group received an IFN-gamma dose of 0.03 mg/m2 and subsequent groups received higher IFN-gamma doses of 0.3, 1, or 3 mg/m2. Toxicity resulting from IFN-gamma was minimal and the therapy was well tolerated even at the maximum dose (3 mg/m2). No patients developed antibodies that neutralized IFN-gamma. Clinical responses were observed in 3 of 17 patients with Kaposi's sarcoma (KS). A complete clinical response was achieved in one individual and a partial, temporary regression of KS lesions was observed in two other patients. HIV p24 antigen was decreased in plasma samples obtained from six of nine patients with initially detectable HIV protein. These data suggest that IFN-gamma should be considered as a therapeutic agent, possibly with other antivirals, in the treatment of patients with AIDS. PMID- 2110973 TI - High-performance liquid chromatographic determination of the enantiomers of flecainide in human plasma and urine. AB - A stereospecific high-performance liquid chromatographic method for the determination of (R,S)-flecainide acetate [(R,S)-N-(2-piperidylmethyl)-2,5-bis (2,2,2-trifluoroethoxy)benzam ide acetate] in human plasma and urine is described. After addition of the internal standard [IS; (R,S)-N-(2 piperidylmethyl)-2,3-bis(2,2,2-trifluoroethoxy)- benzamide hydrochloride], a single-step extraction of alkalinized samples was performed with distilled diethyl ether. The organic layer was evaporated and the drug and IS were derivatized with 1-[(4-nitrophenyl)sulfonyl]-L-propyl chloride at 80 degrees C for 2 h. The diastereomeric derivatives of flecainide and IS were chromatographed on a C18 reversed-phase column with a mobile phase consisting of acetonitrile: water:triethylamine (45:55:0.2) at a flow rate of 1 mL/min. Flecainide diastereomers were separated with a resolution factor of 1.25 and detected by UV spectroscopy at a wavelength of 280 nm. An excellent linearity was observed between the peak area ratios (flecainide derivatives:IS) and plasma concentrations, and the intra- and interday coefficients of variation were always less than 9.8%. The lowest quantifiable concentration was set at 50 ng/mL for each enantiomer (CV of 4.9 and 4.4%), while the lowest limit of detection (signal:noise, 3:1) was on the order of a few nanograms. The assay was used to study the pharmacokinetics of flecainide enantiomers in a patient receiving (R,S) flecainide therapy. The steady-state plasma time courses for the enantiomers were found to be parallel, but the difference between (R)- and (S)-flecainide concentrations was significant. The urinary excretion data were consistent with the plasma results. The method is suitable for therapeutic monitoring of flecainide enantiomers and for stereoselective pharmacokinetic studies in humans. PMID- 2110974 TI - Evaluation of a potent inhibitor of subprimate and primate renins. AB - Our attempts to synthesize a potent inhibitor of rat renin have resulted in the discovery of CGP 44 099 A, a potent inhibitor of plasma renin from all subprimate species tested so far [IC50 (in nM): dog, 0.007; rabbit, 0.033; guinea pig, 0.34; mouse, 0.4; cat, 0.57; and rat, 1.3]. This compound is also a potent inhibitor of primate renins [IC50 (in nM): human, 0.3; and marmoset, 1.4]. It is less potent against other aspartic proteinases [IC50 (in nM): porcine pepsin, 26; and bovine cathepsin D, 230). CGP 44 099 A exhibited a competitive mode of inhibition against human renin (Ki, 0.12 nM). During i.v. infusion of CGP 44 099 A in sodium depleted normotensive rats (0.1 mg/kg/min) blood pressure (BP) was lowered by about 25 mm Hg. Plasma renin activity, angiotensin I and angiotensin II were almost completely suppressed. The converting enzyme inhibitor enalaprilat (1 mg/kg i.v.) also lowered BP by about 25 mm Hg. No further fall in BP occurred when CGP 44 099 A (0.1 mg/kg/min) was infused after pretreatment with enalaprilat (1 mg/kg i.v.) and CGP 44 099 A did not lower BP when infused in bilaterally nephrectomized rats. These results indicate that the hypotensive response induced by CGP 44 099 A in sodium-depleted rats is specifically due to the renin inhibition. Compounds such as CGP 44 099 may therefore be useful for comparing the effects of renin inhibition in different species and for studying the role of renin in various models of cardiovascular disease in nonprimate species. PMID- 2110975 TI - Identification of the subcellular site for nitroglycerin metabolism to nitric oxide in bovine coronary smooth muscle cells. AB - The vasodilating action of nitroglycerin (NTG) is thought to be mediated by its metabolic activation to nitric oxide (NO) in the vascular smooth muscle cell, but the site at which this process occurs has not been defined. To determine which cellular component is primarily responsible for this metabolic activation, subcellular fractions of bovine vascular smooth muscle cells were prepared and incubated with NTG along with cofactors. Time-dependent headspace NO concentrations generated in these preparations were determined directly by chemiluminescence detection. A mathematical model was developed to relate headspace NO with the NO-generating activity in each incubation, correcting for the concurrent processes of NO partitioning between the headspace and the incubation medium, and NO degradation in these two phases. The estimated NO generating activities from different subcellular fractions were well correlated with the activities of two enzyme markers of the plasma membrane (K(+)-activated ouabain sensitive p-nitrophenyl phosphatase and 5'-nucleotidase), but not with those of the mitochondria, endoplasmic reticulum or the cytosol. These results indicate that the enzyme(s) responsible for the metabolic activation of NTG, and possibly other organic nitrate vasodilators, are associated with the plasma membrane in bovine coronary smooth muscle cells. PMID- 2110976 TI - Vasoactive intestinal peptide (VIP) as transmitter of inhibitory motor neurons of the gut: evidence from the use of selective VIP antagonists and VIP antiserum. AB - The role of vasoactive intestinal peptide (VIP) in neurally mediated relaxation of guinea pig and rat intestine was examined with three putative VIP antagonists: a C-terminal sequence of VIP (VIP10-28), substituted analogs of VIP ([4-Cl-D Phe6, Leu17]VIP) and growth hormone releasing factor (GRF) ([Ac-Tyr1, D-Phe2] GRF1-29). The three agents inhibited selectively relaxation induced by VIP and its homolog, peptide histidine isoleucine. Inhibition of VIP-induced relaxation in tenia coli and gastric fundic strips was consistent with competitive antagonism. Relaxation induced by field stimulation (80 V; 1 msec; 0.1-16 Hz) which is accompanied by a stoichiometric increase in VIP release was inhibited by the three antagonists in the following order of potency: VIP10-28 greater than VIP analog greater than GRF analog. The descending relaxation component of the peristaltic reflex induced by graded stretch of the orad end of a rat colonic segment which is also accompanied by an increase in VIP release, was inhibited by the three VIP antagonists in the same order of potency: VIP10-28 greater than VIP analog greater than GRF analog. The most potent antagonist, VIP10-28, abolished descending relaxation at the lowest grades of stretch (2 and 4 g) and inhibited relaxation at the highest grades of stretch (10 g) by 79%. The results indicate that VIP (and peptide histidine isoleucine) is the transmitter responsible for neurally induced gastric and intestinal relaxation. PMID- 2110977 TI - Alterations by glyburide of effects of BRL 34915 and P 1060 on contraction, 86Rb efflux and the maxi-K+ channel in rat portal vein. AB - Effects of the K+ channel blocking agent, glyburide, on the actions of two K+ channel openers, BRL 34915 (cromakalim) and P 1060 (Leo), a potent pinacidil derivative (N-(t-butyl)-N"-cyano-N'-3-pyridyl-guanidine), were ascertained. Tension responses and 86Rb fluxes in rat portal vein strips and single channel electrophysiological recordings in enzymatically dissociated rat portal vein cells were obtained. Glyburide (0.3 microM) increased spontaneous contractile activity and caused concentration-dependent shifts in the relaxation responses to BRL 34915 and P 1060. Increases in 86Rb efflux were obtained only at much higher concentrations of BRL 34915 or P 1060, and these increases were blocked only at higher concentrations of glyburide (5.0 microM). BRL 34915 and P 1060 specifically increase the open-state probability of the Ca+(+)-activated K+ (maxi K+) channel, and these actions are blocked by glyburide and also by charybdotoxin. Changes in single channel activity and contractile responsiveness occur at similar concentrations of agonists and antagonists. Thus, the membrane channel in rat portal vein affected by glyburide, BRL 34915 and P 1060 appears to be the Ca+(+)-activated maxi-K+ channel (that does not show ATP dependence under the conditions of these experiments). Concentrations of agonists and antagonists effective on maxi-K+ channel activity correspond to those affecting contractile responsiveness and are lower than those eliciting changes in 86Rb flux. PMID- 2110978 TI - Dopamine efflux from striatal slices after intracerebral 6-hydroxydopamine: evidence for compensatory hyperactivity of residual terminals. AB - In this study, we have examined the spontaneous efflux and stimulation-induced overflow of endogenous dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) from striatal slices prepared from adult rats. Partial destruction of striatal DA terminals with 6-hydroxydopamine reduced the electrically evoked overflow of DA and DOPAC, but by less than the DA content of the tissue slices. This resulted in an increase in the fractional overflow of DA and DOPAC, a measure of overflow from residual dopaminergic terminals. The increase in fractional DA overflow was related to the lesion size, reaching 7-fold with DA depletions of greater than 90%. Inhibition of DA re-uptake with nomifensine (10 microM) increased DA overflow and reduced DOPAC overflow by an equivalent amount, indicating that a portion of the DA released by electrical stimulation is recaptured and metabolized before appearing as DOPAC in the superfusate. However, 6 hydroxydopamine lesions further elevated fractional DA overflow above control even in the presence of nomifensine, suggesting that slices prepared from lesioned animals exhibit an increase in DA release from residual dopaminergic terminals. DA overflow was enhanced by the DA receptor antagonist sulpiride (1 microM) in control tissue but not in slices prepared from lesioned animals, suggesting that increased efflux per terminal was accompanied by reduced autoinhibition of release. Over a range of firing frequencies typical of nigrostriatal neurons in vivo (2-8 Hz), fractional DA overflow per pulse from lesioned slices was 3-fold higher than control overflow; however, fractional overflow per pulse was reduced from lesioned but not control slices when slices were exposed to a higher frequency (12 Hz). Thus, the lesion appeared to have increased DA release at moderate frequencies, but had reduced the effective range of frequencies over which the DA terminals could operate. Finally, 3-iodotyrosine (2 mM), an inhibitor of tyrosine hydroxylase, reduced DA overflow from intact slices, but completely abolished overflow from lesioned slices, suggesting that 6 hydroxydopamine had increased the dependence of DA efflux on a sustained rate of DA synthesis. Taken together, these data suggest that after lesioning with 6 hydroxydopamine, DA released per pulse from residual terminals is increased relative to control, so long as the stimulation frequency is within the physiological range. This increase in release may serve a compensatory function, maintaining dopaminergic control over striatal function despite extensive loss of DA neurons. PMID- 2110979 TI - Pregnancy zone protein inhibits production of interleukin-2 but does not affect interleukin-2 receptor expression on T cell activation. AB - The effect of pregnancy zone protein (PZP), which exhibits increased levels in the blood during pregnancy, on T cells was examined. PZP was found to suppress DNA synthesis following stimulation with phytohemagglutinin (PHA), concanavalin A (ConA) or CD3 antigen or in the mixed lymphocyte reaction (MLR). This effect of PZP was mediated by a reduction in interleukin-2 (IL-2) production, and was abolished by exogenous recombinant IL-2 administration. PZP did not affect the proliferation of T cells following stimulation with the calcium ionophore A23187 and phorbol 12-myristate 13-acetate (TPA). These results suggest that PZP acts on the T cell surface and reduces IL-2 production, but not IL-2R expression, and does not directly affect Ca2+ influx or protein kinase C. PMID- 2110980 TI - Trichobezoars in two saddleback tamarins (Saguinus fuscicollis). AB - Two captive-born Saddleback tamarins (Saguinus fuscicollis) died unexpectedly in the primate colony at the Peruvian Primatological Project. At necropsy, a firm, mobile, oblong, obscure mass was discovered in the stomach of each. They were removed and determined to be trichobezoars. PMID- 2110981 TI - Characterization of a G-protein beta-subunit gene from the nematode Caenorhabditis elegans. AB - The gene encoding the beta-subunit of guanine nucleotide binding regulatory proteins (G-proteins) has been cloned from the nematode Caenorhabditis elegans. The predicted 340 amino acid sequence matches the highly conserved amino acid sequences of previously isolated G-protein beta-subunits from mammals and Drosophila. The coding region of the C. elegans beta-subunit gene, which has been mapped to the C. elegans chromosome II, is interrupted by eight introns. Southern analysis indicates that C. elegans has only one beta-subunit gene. A 2.8 kb (1 kb = 10(3) bases or base-pairs) transcript derived from this gene could be detected. PMID- 2110982 TI - Serological survey of the Iriomote cat (Felis iriomotensis) in Japan. AB - The Iriomote cat (Felis iriomotensis) was first discovered on Iriomote Island in the Yaeyama Islands of Japan in 1965. Ten male and 11 female adult cats were captured during the 6 yr period from 1983 to 1988. These were examined for evidence of viral and mycoplasmal infections. Neither Mycoplasma sp. nor Ureaplasma sp. were detected in swab samples of oropharyngeal and urogenital regions. A foamy virus was isolated from the oropharyngeal swab of a female cat examined in 1988. Feline leukemia virus was not detected in any of the cats. All cats were negative for serum antibodies to feline panleukopenia virus, feline herpesvirus, feline immunodeficiency virus and rotavirus. Eleven of 19 (58%), 14 of 17 (82%) and 6 of 17 cats (35%) had serum antibodies against feline calicivirus, coronavirus and feline syncytium forming virus, respectively. PMID- 2110983 TI - From the National Institutes of Health. PMID- 2110984 TI - The cost-effectiveness of antihypertensive drugs. PMID- 2110985 TI - Does quality influence choice of hospital? AB - In recent years, much information has been provided to the public and to physicians about hospital quality measured in terms of patient outcomes. To examine if, before these public data releases, quality influenced the attractiveness of a hospital to referring or admitting physicians and to patients, we estimated the influences of quality, charges, ownership, and distance on the choice of hospitals for patients with seven surgical procedures and five medical diagnoses in hospitals in three geographic areas in California in 1983. Greater distance and public or proprietary ownership consistently reduced the likelihood of selection while medical school affiliation increased the likelihood of selection. For five of seven surgical procedures and two of five medical diagnoses, hospitals with poorer than expected outcomes attracted significantly fewer admissions. The reverse held for two surgical procedures and one medical diagnosis. The results suggest that quality played an important role in choices among hospitals even before explicit data were widely available. PMID- 2110986 TI - Quality-adjusted life-years. Ethical implications for physicians and policymakers. AB - Quality-adjusted life-years have been used in economic analyses as a measure of health outcomes, one that reflects both lives saved and patients' valuations of quality of life in alternative health states. The concept of "cost per quality adjusted life year" as a guideline for resource allocation is founded on six ethical assumptions: quality of life can be accurately measured and used, utilitarianism is acceptable, equity and efficiency are compatible, projections of community preferences can substitute for individual preferences, the old have less "capacity to benefit" than the young, and physicians will not use quality adjusted life-years as clinical maxims. Quality-adjusted life-years signal two shifts in the locus of control and the nature of the clinical encounter: first, formal expressions of community preferences and societal usefulness would counterbalance patient autonomy, and second, formal tools of resource allocation and applied decision analysis would counterbalance the use of clinical judgment. These shifts reflect and reinforce a new financial ethos in medical decision making. Presently using quality-adjusted life-years for health policy decisions is problematic and speculative; using quality-adjusted life-years at the bedside is dangerous. PMID- 2110987 TI - [Fluctuation of end-tidal CO2 concentration at rCBF measurement by Xe-133 inhalation and the necessity of its correction for CO2]. PMID- 2110988 TI - [Experimental substantiation of the use of CO2 laser radiation for preventing suppuration of the surgical wound]. AB - It was revealed, that irradiation in the experiment of the spore-forming and non spore-forming microbial cultures, irrespective of the density of growth, was accompanied by their complete destruction in density of radiant energy of the "Scalpel-1" CO2-laser equal to 32.2 J/cm2 (power density--32.2 W/cm2) and more, and exposure for 1 s. PMID- 2110989 TI - [Clinico-morphologic evaluation of the course of the wound process after treatment of suppurative wounds with the CO2 laser]. AB - The complex examination and treatment of 238 patients with suppurative wounds of the soft tissues were carried out. Treating a suppurative wound by means of CO2 laser leads to reduction in microbial colonization of the tissues in its depth, accelerates maturation of granulations, wound cicatrization. The use of CO2-laser permitted to achieve primary healing of 94.3% of the wounds. The average duration of hospital stay of the patients was (9.2 +/- 1.4) days, in control--(11.8 +/- 1.6) days. PMID- 2110990 TI - Augmentation of glucocorticoid action on human monocytes by interleukin-4. AB - For their anti-inflammatory effects, glucocorticoids act, at least in part, by suppression of the production of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha) and prostaglandin E2 (PGE2) by activated monocytes/macrophages. Interleukin-4 (IL-4) also suppresses similar parameters of monocyte activation in vitro. However, contrasting effects of IL-4 and dexamethasone (Dex) on monocyte tissue-type plasminogen activator (t-PA) production suggest that these agents may operate by different pathways. We have now demonstrated that levels of IL-4 as low as 0.05-0.1 U/ml (0.6-1.2 x 10(-11)M) can augment the actions of Dex (5 x 10( 9)M) as an inhibitor of the production of monocyte pro-inflammatory mediators. These in vitro results suggest the possible supplementation of steroid therapy with low amounts of IL-4 (or an agonist) permitting the use of less steroid with concomitant reduction in steroid-associated side-effects. IL-4 can also suppress the increased release of IL-1 beta and TNF alpha by monocytes incubated with indomethacin, a non-steroidal anti-inflammatory drug. PMID- 2110991 TI - The effect of whole body hyperthermia on the immune cell activity of cancer patients. AB - The effect of moderate whole body hyperthermia (WBH) on the immunological responses of cancer patients was studied by monitoring their peripheral blood mononuclear cells (PBMC) in vitro. WBH of 2 degrees C above normal body temperature was induced in patients by utilizing a 433 MHz microwave system with a series of 6-9 external antennae. A total of three treatments were given with a frequency of one per week. Blood samples were drawn before treatment, when the target temperature was attained, and one hour after heating was discontinued. Changes in the number of PBMC, the mitogenic response, natural killer cell activity, and the production of Interleukin-1, Interleukin-2, and Interferon (IL 1, IL-2, IF) were measured in vitro. Mitogenic responses were increased 2-3 fold when the temperature was raised. Although there was an increase in the number of PBMC, during the course of heating, repeated treatment resulted in a selective and transient reduction in the number of PBMC. Nevertheless, the PBMC were capable of producing a higher level of cytokines and attained an enhanced ability to destroy target cells in vitro. The results indicate that, by inducing a fever like condition, the immunological responses are enhanced in vitro. PMID- 2110992 TI - Predicting utilization of home health resources. Important data from routinely collected information. AB - This study examined the feasibility of using routinely collected information on patients enrolled in home health care to predict their subsequent use of services. Data were gathered from 1,984 episodes of care randomly sampled from home health care agencies of the Virginia Health Department. Age, sex, Medicare and Medicaid enrollment, referral source, medical diagnosis, and prognosis were used to predict the total number of visits, the duration of enrollment, and the intensity of service. Since the data were originally gathered to study the effects of the implementation of diagnosis-related groups (DRGs) on home health services, half of the patients were enrolled before and half after the implementation of DRGs. Using multiple linear regression analysis, significant amounts of variance in each measure of home health care utilization were explained by the predictor variables (R2 = 0.04 to 0.10). For example, after controlling for other predictor variables, age 75 years or older predicted longer durations of enrollment and lower intensities of service as compared with other age groups (P less than 0.05), and four of 14 diagnosis categories predicted at least one measure of utilization (P less than 0.05). Medicaid enrollment predicted longer durations of enrollment and lower intensities of service in home health care (P less than 0.05) in the post-DRG but not the pre-DRG period. These results demonstrate the value of routinely collected information in predicting the use of home health services. To develop more accurate estimates of needs for home health services for particular groups of patients, additional information on chronic functional impairments, informal caregiving, and the chronicity of needs may be useful. PMID- 2110993 TI - Health care costs for employed hypertensives. AB - Health care insurance claims were used to track costs associated with hypertension for an employed population. Employees were classified as hypertensive (n = 373), high normal (n = 363), or normotensive (n = 2,411) on the basis of hypertension screening done at the worksite. Claims activity was monitored for the three groups during a three-year period, including periods before, during, and after the screening done at the worksite. The average amount claimed per employee was significantly higher for the hypertensives as compared with the normotensives or high normals, even after adjustment for age, race, sex, salary, marital status, and duration of insurance coverage. There was no significant difference in the average amount claimed per employee between high normals and normotensives. The health care costs for hypertensives are estimated to be about 80% more than those for normotensives. Hospital, physicians, and nursing care accounts for about 50 percentage points of this increment while the remaining 30 percentage points derive from drug costs. PMID- 2110994 TI - [Medical ethics. Social medicine and moral philosophy--an analysis of mandatory psychiatric care]. PMID- 2110995 TI - [Patients with acute Crohn disease can be treated with nasogastric sond nutrition]. PMID- 2110996 TI - The regulation of transcription of the gerA spore germination operon of Bacillus subtilis. AB - The gerA operon of Bacillus subtilis 168 comprises three genes concerned with the triggering of spore germination by L-alanine and its analogues. The expression of this operon has been characterized using chromosomal lacZ fusions to the gerA promoter. The gerA promoter is switched on 2.5-3 hours after the initiation of sporulation, in parallel with glucose dehydrogenase. A high proportion of the gerA-driven beta-galactosidase detected in sporulating cells is found in the mature spore; the gerA promoter is therefore active in the forespore compartment of the sporulating cell. The gerA promoter is not expressed in spoO, spoII or spoIIIA, B, E and G mutant backgrounds, but is expressed in spoIIIC and D and in spoIV and V mutants. The in vivo transcriptional startpoint of the operon has been mapped by primer extension experiments; sequences upstream from this startpoint show significant homology with recognition sequences for RNA polymerase containing sigma G (E sigma G). The gerA operon was transcribed in vitro by E sigma G with a startpoint identical to that used in vivo, and expression of the gerA operon was rapidly induced in vegetative cells by induction of sigma G synthesis. These data indicate that the gerA operon is an additional member of the sigma G regulon, which includes a number of genes expressed in parallel only in the forespore compartment of sporulating B. subtilis cells. PMID- 2110997 TI - Pro-subtilisin E: purification and characterization of its autoprocessing to active subtilisin E in vitro. AB - The formation of active subtilisin E from pro-subtilisin E requires the removal of the N-terminal pro-sequence of 77 residues. Pro-subtilisin E produced in Escherichia coli using a pINIII-ompA vector was first extracted with 6 M guanidine-HCl and 5 M urea and purified to homogeneity in the presence of 5 M urea. Upon drop dialysis against 0.2 M sodium phosphate buffer (pH 6.2), the purified pro-subtilisin in 5 M urea was processed to active subtilisin of which the N-terminal sequence and migration in SDS-polyacrylamide gel electrophoresis were identical to those of authentic active subtilisin E. This process was found to be very sensitive to the ionic strengths and anions used. Under the optimum conditions (dialysis against 0.5 M (NH4)2SO4 and 1 mM CaCl2 in 10 mM Tris-HCl buffer (pH 7.0) at 4 degrees C for 1 h), approximately 20% of pro-subtilisin E was converted to active subtilisin E. The activation process was not inhibited by Streptomyces subtilisin inhibitor, and pro-subtilisin E in which the active site was mutated (Asp32 to Asn) was unable to be processed under the optimum conditions. These results confirmed the previous hypothesis that the processing of pro-subtilisin occurs by an intramolecular, autoprocessing mechanism. PMID- 2110998 TI - Isolation of a secY homologue from Bacillus subtilis: evidence for a common protein export pathway in eubacteria. AB - Genetic and biochemical studies have shown that the product of the Escherichia coli secY gene is an integral membrane protein with a central role in protein secretion. We found the Bacillus subtilis secY homologue within the spc-alpha ribosomal protein operon at the same position occupied by E. coli secY. B. subtilis secY coded for a hypothetical product 41% identical to E. coli SecY, a protein thought to contain 10 membrane-spanning segments and 11 hydrophilic regions, six of which are exposed to the cytoplasm and five to the periplasm. We predicted similar segments in B. subtilis SecY, and the primary sequences of the second and third cytoplasmic regions and the first, second, fourth, fifth, seventh, and tenth membrane segments were particularly conserved, sharing greater than 50% identity with E. coli SecY. We propose that the conserved cytoplasmic regions interact with similar cytoplasmic secretion factors in both organisms and that the conserved membrane-spanning segments actively participate in protein export. Our results suggest that despite the evolutionary differences reflected in cell wall architecture, Gram-negative and Gram-positive bacteria possess a similar protein export apparatus. PMID- 2110999 TI - State laws restricting minors' access to tobacco. PMID- 2111000 TI - Measles--United States, 1989 and first 20 weeks 1990. PMID- 2111001 TI - Perinatal mortality and congenital malformations in infants born to women with insulin-dependent diabetes mellitus--United States, Canada, and Europe, 1940 1988. PMID- 2111002 TI - Cholera--worldwide, 1989. PMID- 2111003 TI - Occupational safety and health guidelines for chemical hazards. PMID- 2111004 TI - Cloning and nucleotide sequence of the gene braB coding for the sodium-coupled branched-chain amino acid carrier in Pseudomonas aeruginosa PAO. AB - The gene braB, encoding the Na(+)-coupled carrier for branched-chain amino acids in Pseudomonas aeruginosa PAO, was cloned on cosmid pMMB34. The cosmid clones carrying the braB gene were identified as those that restored growth at low leucine concentration and Na(+)-dependent leucine transport activity to P. aeruginosa PAO3536 defective in the transport of branched-chain amino acids. Determination of the nucleotide sequence of the DNA fragment shows that the braB gene comprises 1311 bp and encodes a hydrophobic protein of 437 amino acids with a calculated Mr of 45,279. The hydropathy profile suggests that there exist in the carrier protein 12 hydrophobic segments long enough to traverse the membrane. The amino acid sequence shows a high degree of homology with the brnQ product, a branched-chain amino acid carrier of Salmonella typhimurium, while no homology in the nucleotide sequences is found in the braB and brnQ genes. PMID- 2111005 TI - Valproate and palmitate binding to human serum albumin: an hypothesis on obesity. AB - Binding equilibria of valproate (2-n-propyl-pentanoic acid anion) with defatted human serum albumin were studied by equilibrium dialysis in a 66 mM sodium phosphate buffer, pH 7.4, 37 degrees. Three hundred and fifty-six observed points for bound versus free valproate concentration were obtained and analyzed in terms of stepwise binding. It was found that the best fit resulted from a model in which 67% of the albumin was capable of binding valproate, whereas 33% did not bind. Thirty acceptable variants of the curve fitting were generated in order to assess the variation of the binding constants. The binding albumin component combines with three molecules of valproate with high affinity and with at least seven additional molecules that are loosely bound. Saturation of the protein cannot be reached. At very high concentrations of free valproate (above 10 mM) irreversible changes in the albumin take place, resulting in poor reproducibility in the amount of bound valproate. In the presence of palmitate, 0.5, 1, and 1.5 mol/mol of albumin, binding of valproate is decreased by a competitive mechanism. It is hypothesized that obesity, developing as a complication of valproate treatment of epilepsy, results from increased availability of long-chain fatty acids due to competitive valproate binding. PMID- 2111006 TI - Gargoylism. PMID- 2111007 TI - Purulent tendon sheath infection. PMID- 2111008 TI - Nuclear matrix attachment occurs in several regions of the IgH locus. AB - The genome is thought to be divided into domains by DNA elements which mediate anchorage of chromosomal DNA to the nuclear matrix or chromosome scaffold. The positions of nuclear matrix anchorage regions (MARs) have been mapped within the 200 kb mouse immunoglobulin heavy chain constant region locus, thereby allowing an estimate of the size of DNA domains within a segment of the genome. MARs were identified in four regions, which appear to divide the locus into looped DNA domains of 30, 20, 30 and greater than 70 kb in length. These DNA domain sizes fall within the range of DNA loop sizes observed in histone-extracted nuclei and chromosomes. In two regions, large clusters of MARs were identified, and many of these MARs lie on DNA fragments that include repetitive DNA elements, perhaps indicating that repetitive DNA integrates into the genome close to MARs, or that some classes of repeats could themselves act as MARs. PMID- 2111010 TI - Nucleotide sequence of the cDNA encoding human tyrosinase-related protein. PMID- 2111009 TI - The serum and TPA responsive promoter and intron-exon structure of EGR2, a human early growth response gene encoding a zinc finger protein. AB - EGR2 is a human zinc finger encoding gene whose expression is induced with fos like kinetics by diverse mitogens in several cell types. Since its cDNA sequence predicts a protein which contains zinc finger motifs, EGR2 may play a transcriptional regulatory role in cellular proliferation. The present study was undertaken to: 1) examine the genomic organization and 5' flanking sequence of EGR2 so as to identify upstream regulatory elements; 2) test whether these elements are functional in gel shift assays and by transient expression; and 3) examine whether pathways other than protein kinase C lead to serum induction of EGR2, and if they do, ask whether the different pathways converge on a serum response element. The EGR2 gene spans 4.3 kb and has one intron. The translation initiation site is located within the first exon. The transcription start site of EGR2 was determined by S1 nuclease and primer extension analysis and a TATA box was identified 28 bp upstream. Two putative serum response elements, designated CArG-1 and CArG-2 were identified in the 5' flanking sequence. By deletion analyses and mutagenesis, serum and PMA responsiveness of the cloned EGR2 promoter region was traced to the CArG-1 region in transient CAT assays performed in NIH 3T3 cells. Both protein kinase C dependent and independent pathways were found to converge on the CArG-1 box to induce the expression of EGR2. PMID- 2111011 TI - Nucleotide sequence of a tRNA cluster from Mycoplasma pneumoniae. PMID- 2111012 TI - Purification and properties of Myxococcus xanthus C-factor, an intercellular signaling protein. AB - C-factor, a Myxococcus xanthus protein that restores the developmental defects of a class of nonautonomous mutants resulting from mutation of the csgA gene, has been purified approximately 1000-fold from starved wild-type cells. The monomeric form of C-factor is a single polypeptide with a molecular mass of 17 kDa that can be solubilized by detergent from membrane components. Characterization by gel filtration and denaturing gel electrophoresis suggests that biologically active C factor is a dimer composed of two 17-kDa monomers. Antibodies against a form of the M. xanthus csgA gene product overexpressed in Escherichia coli react with purified C-factor. PMID- 2111013 TI - 2-Azido-[32P]NAD+, a photoactivatable probe for G-protein structure: evidence for holotransducin oligomers in which the ADP-ribosylated carboxyl terminus of alpha interacts with both alpha and gamma subunits. AB - A radioactive and photoactivatable derivative of NAD+, 2-azido-[adenylate 32P]NAD+, has been synthesized and used with pertussis toxin to ADP-ribosylate Cys347 of the alpha subunit (alpha T) of GT, the retinal guanine nucleotide binding protein. ADP-ribosylation of alpha T followed by light activation of the azide moiety of 2-azido-[adenylate-32P]ADP-ribose produced four crosslinked species involving the alpha and gamma subunits of the GT heterotrimer: an alpha trimer (alpha-alpha-alpha), and alpha-alpha-gamma crosslink, an alpha dimer (alpha-alpha), and an alpha-gamma crosslink. The alpha trimer, alpha-alpha-gamma complex, alpha dimer, and alpha-gamma complexes were immunoreactive with alpha T antibodies. The alpha-alpha-gamma and the alpha-gamma complexes were immunoreactive with antisera recognizing gamma subunits. No evidence was found for crosslinking of alpha T to beta T subunits. Hydrolysis of the thioglycosidic bond between Cys347 and 2-azido-[adenylate-32P]ADP-ribose using mercuric acetate resulted in the transfer of radiolabel from Cys347 of alpha T in the crosslinked oligomers to alpha monomers, indicative of intermolecular photocrosslinking, and to gamma monomers, indicative of either intermolecular crosslinked complexes (between heterotrimers) or intramolecular crosslinked complexes (within the heterotrimer). These results demonstrate that GT exists as an oligomer and that ADP-ribosylated Cys347, which is four residues from the alpha T-carboxyl terminus, is oriented toward and in close proximity to the gamma subunit. PMID- 2111014 TI - Binding of substrate CO2 to the active site of human carbonic anhydrase II: a molecular dynamics study. AB - Molecular dynamics has been used to study binding of substrate CO2 to the active site of human carbonic anhydrase II. Three potential CO2 binding sites have been located. The first is at the active-site hydrophobic pocket (the catalytically productive site), where CO2 is approximately 3.5 A from the zinc ion and interacts with His-94, His-119, Val-121, Val-143, Leu-198, Thr-199, the zinc ion, and the zinc-bound hydroxide ion. The second CO2 binding site is approximately 6 A from the zinc ion, where CO2 interacts with His-64, His-94, Leu-198, Thr-200, Pro-201, Pro-202, and some active-site water molecules. The third CO2 binding site is approximately 10 A from the zinc ion, is largely solvated by water molecules, and interacts with His-64, Asn-67, and Gln-92. At these three CO2 binding sites, the CO2 molecule is highly localized (the average Zn-CO2 distance fluctuation is approximately 1 A) and favors the linear binding orientation toward the zinc ion. This linear binding orientation of CO2 and its electrostatic interaction with the zinc ion direct diffusion of CO2 toward the zinc ion and facilitate the nucleophilic attack from O of the zinc-bound OH- to C of CO2 in the productive hydrophobic binding site. Finally, the two CO2 binding sites outside the hydrophobic binding pocket, which may represent two intermediate states along the CO2 binding pathway, could play important roles as a CO2 relay. PMID- 2111015 TI - An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. AB - Interferons (IFNs) induce transcription of major histocompatibility complex (MHC) class I genes through the conserved IFN consensus sequence (ICS) that contains an IFN response motif shared by many IFN-regulated genes. By screening mouse lambda ZAP expression libraries with the ICS as a probe, we isolated a cDNA clone encoding a protein that binds the ICS, designated ICSBP. Protein blot analysis with labeled oligonucleotide probes showed that ICSBP binds not only the MHC class I ICS but also IFN response motifs of many IFN-regulated genes, as well as a virus-inducible element of the IFN-beta gene. The ICSBP cDNA encodes 424 amino acids and a long 3' untranslated sequence. The N-terminal 115 amino acids correspond to a putative DNA-binding domain and show significant sequence similarity with other cloned IFN response factors (IRF-1 and IRF-2). Because of the structural similarity and shared binding specificity, we conclude that ICSBP is a third member of the IRF gene family, presumably playing a role in IFN- and virus-mediated regulation of many genes. Although IRF-1 and IRF-2 share some similarity in their C-terminal regions, ICSBP shows no similarity to IRF-1 or IRF 2 in this region, suggesting that it is more distantly related. We show that ICSBP mRNA is expressed predominantly in lymphoid tissues and is inducible preferentially by IFN-gamma. The induction by IFN-gamma appears to be predominant in lymphocytes and macrophages, implying that ICSBP plays a regulatory role in cells of the immune system. The presence of multiple factors that bind common IFN response motifs may partly account for the complexity and diversity of IFN action as well as IFN-regulated gene expression. PMID- 2111016 TI - Autogenous regulation of the Bordetella pertussis bvgABC operon. AB - The bvgABC operon of the bacterial pathogen Bordetella pertussis encodes a sensory transduction system that regulates the expression of several virulence genes in response to environmental stimuli. In this study we have examined the transcriptional regulation of the bvgABC operon. Transcriptional bvg::lacZYA fusions in Escherichia coli show that the bvgABC operon is autogenously activated. Autoactivation is inhibited by the same environmental stimuli that result in the lack of expression of bvg-activated genes in B. pertussis. These observations were confirmed in B. pertussis using a chromosomal chloramphenicol acetyltransferase transcriptional fusion in bvgC. Transcriptional initiation sites upstream of bvgA were mapped by primer extension analysis in E. coli and B. pertussis. Two differentially regulated bvg promoters were identified. The bvgP1 promoter is a positively autoregulated promoter located 90 base pairs upstream of bvgA. The bvgP2 promoter is located 141 base pairs upstream of bvgA and does not appear to require any positive regulatory factors for activity. These results suggest a model describing the regulatory events that take place upstream of the bvgABC operon. PMID- 2111017 TI - Trans-dominant negative mutants of Fos and Jun. AB - Jun and Fos nuclear oncoproteins form a complex that regulates transcription from promoters containing activator protein AP-1 binding sites. The leucine-zipper and basic-region domains of both Fos and Jun are necessary for formation of the heterodimer that binds to DNA. Reciprocal mutations in the basic region of Fos or Jun can influence the binding of the heterodimer to DNA, implying a symmetrical binding site. DNA-binding mutants of Jun exhibit increased affinity for Fos and are capable of suppressing wild-type Fos-Jun DNA-binding activity. In contrast, mutations in the basic domain of Fos, which prevent binding to DNA in association with Jun, do not significantly diminish the ability of the wild-type heterodimer to bind to DNA. These dominant negative mutants are functional in vivo and can be exploited to study the role of Fos and Jun in normal and transformed cells. PMID- 2111018 TI - Molecular cloning and characterization of GPA1, a G protein alpha subunit gene from Arabidopsis thaliana. AB - We have isolated a gene coding for a G protein alpha subunit from the flowering plant Arabidopsis thaliana. This gene, named GPA1, was isolated by using a DNA probe generated by polymerase chain reaction based on protein sequences from mammalian and yeast G protein alpha subunits. The sequences of genomic and cDNA clones indicate that GPA1 has 14 exons, and the deduced amino acid sequence shows that the GPA1 gene product (GP alpha 1) has 383 amino acid residues (44,582 Da). The GP alpha 1 protein exhibits similarity to all known G protein alpha subunits- 36% of its amino acids are identical and 73% are similar (identical and conservative changes) to mammalian inhibitory guanine nucleotide-binding regulatory factor alpha subunits and transducins. Furthermore, the GP alpha 1 protein has all of the consensus regions for a GTP-binding protein. The GPA1 encoded mRNA of 1.55 kilobases is most abundant in vegetative plant tissues, as determined by RNA blot analysis. Restriction fragment length polymorphism mapping experiments show that GPA1 is approximately 1.2 centimorgans from the visible marker er on chromosome 2. PMID- 2111019 TI - Transcriptional activation of a conserved sequence element by ras requires a nuclear factor distinct from c-fos or c-jun. AB - The expression of transforming growth factor beta type 1 mRNA was increased by conditional expression of ras. A 31-base-pair sequence found approximately 420 base pairs upstream of the gene encoding human transforming growth factor beta 1 acted as a ras-responsive enhancer element in transient transfection assays. The human sequence contains the element TGACTCT that also is found in a murine ras responsive enhancer. Analysis of nuclear factors present in cells stably transformed by ras indicated that both human and murine sequences were recognized by the same nuclear factor. The role of fos and jun in ras transcriptional activation was analyzed in transfection assays using murine elements that contained either TGACTCT or TGAGTAA. These experiments showed that while both elements are activated by fos/jun expression to nearly the same event, only the former element responded to ras. In addition, activation of reporters containing TGACTCT is 6-fold higher by ras than by fos/jun. Gel retention experiments revealed that the nuclear factor present in cells transformed by ras exhibited the same sequence preference as demonstrated in the transient transfection assays. UV-crosslinking experiments identify a protein of apparent molecular mass 120 kDa that recognizes the ras-responsive element. This work identifies a persistent signal transduction pathway that links ras to nuclear transcription and indicates that a 120-kDa protein is a target of this pathway. PMID- 2111020 TI - Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos. AB - Lesion of the sciatic nerve caused a rapid increase in c-fos and c-jun mRNA that was followed about 2 hr later by an increase in nerve growth factor (NGF) mRNA. To evaluate whether the initial increase in c-fos mRNA is causally related to the subsequent increase in NGF mRNA, we performed experiments with fibroblasts of transgenic mice carrying an exogenous c-fos gene under the control of a metallothionein promoter. In primary cultures of these fibroblasts, CdCl2 evoked a rapid increase in exogenous c-fos mRNA, followed immediately by an increase in endogenous c-jun mRNA and with a slight delay by an increase in NGF mRNA. In fibroblasts of C3H control mice, CdCl2 had no effect on the mRNA levels of the protooncogenes c-fos and c-jun or of NGF. Additional evidence for a causal relationship between c-fos induction and the subsequent increase in NGF mRNA was obtained in cotransfection experiments. Fibroblasts of C3H control mice were cotransfected with a metallothionein-promoter-driven c-fos expression vector and a NGF promoter-chloramphenicol acetyltransferase reporter gene construct. Induction of the exogenous c-fos by CdCl2 resulted in increased activity of the NGF promoter. DNase I footprint experiments demonstrated that a binding site for transcription factor AP-1 (Fos/Jun heterodimer) in the first intron of the NGF gene was protected following c-fos induction. That this protected AP-1 site indeed was functional in the regulation of NGF expression was verified by deletion experiments and by a point mutation in the corresponding AP-1 binding region in the NGF promoter-chloramphenicol acetyltransferase reporter construct. PMID- 2111021 TI - Correction of murine mucopolysaccharidosis VII by a human beta-glucuronidase transgene. AB - We recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of beta-glucuronidase (beta-D-glucuronoside glucuronosohydrolase, EC 3.2.1.31). Affected mice, of genotype gusmps/gusmps, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarge vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report we describe the consequences of introducing the human beta-glucuronidase gene, GUSB, into gusmps/gusmps mice that produce virtually no murine beta-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human beta glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gusmps/gusmps mice and that human beta-glucuronidase corrects the murine mucopolysaccharidosis storage disease. PMID- 2111022 TI - High-level production of a functional immunoglobulin heterodimer in a baculovirus expression system. AB - A murine immunoglobulin heterodimer has been expressed in a baculovirus expression system. This was achieved by using both double infection of insect cells with separate heavy- and light-chain-expressing viruses and infection with a double-recombinant virus containing both the immunoglobulin heavy- and light chain cDNAs. In both cases, the polypeptide chains were correctly processed, glycosylated, and assembled into normal H2L2 (H = heavy, L = light) immunoglobulin monomers. These molecules bound antigen and expressed both polyclonal idiotype and monoclonal idiotopes. Furthermore, the transfer vectors described have been modified to contain the F1 origin of replication for the production of single-stranded DNA, which facilitates site-specific mutations of either the polyhedrin promoter or the inserted foreign gene. Use of this system should significantly advance the analysis of the structural bases for both idiotype expression and antigen binding by immunoglobulin. More importantly, it provides a generic method for the high-level expression of antibodies of diverse interest. PMID- 2111023 TI - Different configurational states of beta-amyloid and their distributions relative to plaques and tangles in Alzheimer disease. AB - Antibodies have been raised against synthetic peptides corresponding to different parts of the beta-amyloid sequence. These antibodies stain different kinds of amyloid distributions in the hippocampal formation in Alzheimer disease, suggesting the existence of different states of aggregation and/or folding of beta-amyloid molecules. An antibody directed against the middle region of beta amyloid stained mostly amyloid plaques without cores, whereas an antibody directed against the carboxyl-terminal region of beta-amyloid stained only amyloid plaques with cores. An antiserum directed against the amino terminus of beta-amyloid stained numerous tangle-bearing cells and bodies, as well as the neuritic component of plaques and neuropil threads. These antibodies, in conjunction with anti-tau antibodies, were used to demonstrate a close spatial relationship between amyloid deposits and neurofibrillary tangles. PMID- 2111024 TI - Polyclonal B-cell activation reveals antibodies against human immunodeficiency virus type 1 (HIV-1) in HIV-1-seronegative individuals. AB - Identification of human immunodeficiency virus type 1 (HIV-1)-infected individuals is of paramount importance for the control of the spread of AIDS worldwide. Currently, the vast majority of screening centers throughout the world rely on serological techniques. As such, clinically asymptomatic but HIV infected, seronegative individuals are rarely identified. In this report we show that 18% (30/165) of seronegative individuals who were considered to be a unique cohort of patients at high risk for HIV infection had circulating B cells that, upon in vitro polyclonal activation with pokeweed mitogen, produced antibodies reactive with HIV. Furthermore, polymerase chain reaction analysis of DNA obtained from aliquots of the peripheral blood mononuclear cells from these seronegative but pokeweed mitogen assay-positive individuals tested revealed the presence of HIV-specific sequences in a significant number of samples. In addition, depletion of CD8+ T cells from peripheral blood mononuclear cells of HIV-1-seronegative individuals prior to in vitro culture with pokeweed mitogen resulted in increased sensitivity for detecting HIV-reactive antibodies. This assay has obvious epidemiological implications, especially in the case of high risk groups, and also provides a simple technique to enhance detection of HIV infected individuals. Of further interest is the determination of the mechanisms related to the lack of HIV-specific antibodies in the serum of these infected individuals. PMID- 2111025 TI - Effects of oxysterols on arachidonic acid metabolism and prostacyclin synthesis in bovine aortic smooth muscle cells in culture. AB - Previous studies have shown that oxysterols could induce arterial damage in animals and manifest potent toxicity in cultured cells. Bovine aortic smooth muscle cells in culture were used to study the effects of several cholesterol oxides on arachidonic acid (AA) metabolism. Using two different methods, i.e. radioactive labeling of cells with 14C-AA and radioimmunoassay of 6kPGF1 alpha, the stable metabolite of Prostacyclin (PGI2), we observed various effects depending on the substance. Oxysterols oxidised on the rings were able to inhibit AA metabolism only at high doses, toxic to the cells, presumably through a non specific lytic mechanism. Oxysterols oxidised on the side chain induced an inhibition of the overall arachidonate conversion and PGI2 synthesis at low doses, below the range of cytotoxicity. This inhibition was noted both on the basal and stimulated metabolism. Mechanisms involved in such actions are still to be determined. PMID- 2111026 TI - Comparative effects of some 3-amino 4,6-diarylpyridazines on the biosynthesis in vitro of TXA2 and PGI2- and on the TXA2- and PGI2-synthesizing activities of cardiac tissue. AB - Some 3-amino 4,6-diarylpyridazine derivatives were tested for their effects on TXA2 and PGI2 biosyntheses in vitro and on the TXA2- and PGI2-synthesizing activities of cardiac tissue. Horse platelet and aorta microsomes were used as sources of thromboxane and prostacyclin synthetases respectively. The TXA2- and PGI2-synthesizing activities of cardiac tissue were studied on isolated perfused rabbit hearts (the heart microsomes being used both as TXA2 synthetase and PGI2 synthetase sources). TXB2 and 6-keto PGF1 alpha were determined by RIA. Among the compounds under study, 3-morpholino 4,6-diphenylpyridazine (III) was shown to inhibit specifically the TXA2 synthetase. Substitution of the morpholino group by a dimethylamino one (I) reinforced the inhibiting effects on TXA2 synthetase but it also revealed a slight anti-prostacyclin synthetase action of the molecule. Replacement of 3-morpholino moieties by either a 3-hydrazino (IV), or a 2 dimethylaminoethylamino (V), or a 2-morpholinoethylamino group (VI) abolished completely the effects of the molecule on TXA2 and PGI2 synthetases. Likewise the addition of chlorine on the para-position on the phenyl ring of I neutralized all its inhibitory effects both on TXA2 and PGI2 synthetases in vitro. None of the 3 amino 4,6-diarylpyridazine derivatives was active on either the TXA2- or PGI2 synthesizing activities of cardiac tissue. PMID- 2111027 TI - Antiasthmatic effects of onions: inhibition of 5-lipoxygenase and cyclooxygenase in vitro by thiosulfinates and "Cepaenes". AB - Nine thiosulfinates (TS) and four "Cepaenes" (CS) isolated from onions and/or synthetized by us showed dose dependent (0.25 to 100 microM) marked inhibitory effects on both cyclooxygenase (CA, tested on sheep seminal vesicle microsomes) and 5-lipoxygenase activity (LO, tested on porcine leukocytes). The following rank order of activity was observed: saturated aliphatic TS less than aromatic TS approximately alpha, beta-unsaturated TS less than CS. CS inhibited both CA and LO by more than 75% at 10 and 1 microM concentrations respectively. Most likely, these in vitro effects are responsible for antiinflammatory and antiasthmatic properties of onion extracts observed in vivo, at least in part. PMID- 2111028 TI - Actions of ORG 5222 as a novel psychotropic agent. AB - ORG 5222 is a tetracyclic compound with high affinity for dopamine and 5-HT2 receptors. ORG 5222 was compared to fluphenazine in behavioural tests and was shown to be less potent to cause catalepsy on peripheral administration or to induce asymmetric body posturing following intrastriatal injection. On injection into the nucleus accumbens, ORG 5222 antagonised spontaneous and amphetamine induced hyperactivity. The peripheral administration of ORG 5222 antagonised the hyperactivity induced by infusion of dopamine into the nucleus accumbens of rat or ventral striatum of the marmoset and, unlike the use of fluphenazine, there was no evidence of a 'rebound' hyperactivity after discontinuation of treatment. Furthermore, ORG 5222 prevented changes in responsiveness to dopamine agonist challenge following dopamine infusion. In a mouse black and white test box and the rat elevated plus maze ORG 5222 released exploratory behaviour suppressed by the aversive white or elevated environments. It is concluded that ORG 5222 is effective to antagonise mesolimbic dopamine function in the rodent and primate and an aversive behaviour in rodent tests. Such effects reveal a novel profile of action of ORG 5222 in behavioural paradigms predictive of antipsychotic and anxiolytic potential and may relate to a dopamine and 5-HT receptor antagonism. PMID- 2111029 TI - Dependence-producing properties of alprazolam in the dog. AB - Alprazolam (48 mg/kg/day) administered orally to dogs 4 times a day in equally divided doses produced physical dependence. This dependence was revealed by a precipitated abstinence syndrome which occurred after either oral administration of flumazenil (6, 18 and 36 mg/kg) or intravenous administration of a liposomal suspension of flumazenil. Flumazenil alone (18, 36 and 72 mg/kg) produced no significant signs of precipitated abstinence in naive dogs. This precipitated abstinence syndrome in alprazolam-dependent dogs was characterized by both clonic and tonic-clonic seizures. Other signs of precipitated abstinence which comprise the NPAS score were less intense in the alprazolam-dependent than in diazepam dependent dogs. Alprazolam is extensively metabolized in the dog and does not accumulate whereas its predominant metabolite, alpha hydroxyalprazolam, does accumulate. The data suggest that alpha hydroxyalprazolam plays a role in the dependence-producing properties of alprazolam in the dog as revealed by the precipitated abstinence syndrome. PMID- 2111030 TI - Effects of a new TRH analogue, YM-14673, on disturbance of passive avoidance learning in senescence-accelerated mice. AB - Effects of a new TRH analogue, YM-14673 (N alpha-[[(S)-4-oxo-2 azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), on disturbance of passive avoidance behavior were observed in senescence-accelerated mice (SAM). Latency of step-through in SAM-P/8/Ta (SAM-P/8, senescence-prone substrain) was significantly shorter than that in SAM-R/1/Ta (SAM-R/1, senescence-resistant substrain). Successive oral administration of YM-14673 (1 and 10 mg/kg) and TRH (10 mg/kg) for 3 weeks prolonged the shortened latency of step-through. These results suggest that YM-14673 is more potent than TRH in antiamnesic activities. PMID- 2111031 TI - New pyrimidine-Mannich bases of possible schistosomicidal activity. PMID- 2111033 TI - Diagnosis-related groups: a twentieth-century nosology. PMID- 2111032 TI - [Antitubercular agents. 49. Thiohydrazides, potential antitubercular agents]. PMID- 2111034 TI - Prostacyclin and thromboxane synthesis by endometrial cancer and leiomyomas. AB - To study the role of prostacyclin (PGI2) and thromboxane A2 (TxA2) in uterine tumors, pieces of endometrial cancer (n = 12) and leiomyomas (n = 12) were incubated in vitro, and the productions of 6-keto-prostaglandin F1a (6-keto PGF1a, a hydration product of PGI2) and thromboxane B2 (TxB2, a hydration product of TxA2), measured by radioimmunoassay, were compared to those of corresponding healthy tissues. The production of 6-keto-PGF1a by endometrial cancer (20.8; 15.1 85.0 ng/mg protein/min, median and interquartile range), by healthy endometrium (25.5; 10.0-55.0), by healthy myometrium (34.9; 25.0-59.9) and by leiomyoma (20.3; 10.2-45.1) was similar. The production of TxB2 was increased by endometrial cancer (55.5; 10.5-155.2, p less than 0.02) in comparison with endometrium (9.8; 4.3-35.1), myometrium (3.8; 2.1-8.0) and leiomyoma (1.9; 1.0 3.8). The 6-keto-PGF1a/TxB2 ratio in endometrial cancer (0.9; 0.3-1.5) was smaller (p less than 0.02) than that in healthy endometrium (3.3; 1.9-4.8). Thus, TxA2 may be a factor in endometrial cancer. PMID- 2111035 TI - Prostacyclin synthesis elicited by cholinergic agonists is linked to activation of M2 alpha and M2 beta muscarinic receptors in the rabbit aorta. AB - This study was conducted to investigate the subtypes of muscarinic receptors involved in the action of cholinergic agents on prostacyclin synthesis in the rabbit aorta. Prostacyclin production measured as 6-keto-PGF1 alpha was assessed after exposing the aortic rings to different cholinergic agents. Acetylcholine (ACh) (M1 and M2 agonist) (1-10 microM) and arecaidine proparagyl ester (APE) (M2 selective agonist) (1-10 microM) enhanced 6-keto-PGF1 alpha output in a concentration-dependent manner. A selective M1 receptor agonist, McN-A-343, at 1 microM-1 mM did not alter 6-keto-PGF1 alpha output. ACh- and APE induced increases in 6-keto-PGF1 alpha output were attenuated by the M1/M2 antagonist atropine (0.1 microM), M2 alpha antagonist (AF-DX 116), (0.1-1.0 microM), and by selective M2 beta antagonist, hexahydro-sila-difendiol (HHSiD) (0.1-1.0 microM), but not by the M1 antagonist pirenzepine (1.0 microM). 6-Keto-PGF1 alpha output elicited by ACh- or APE was not altered by the adrenergic receptor antagonists phentolamine and propranolol or by the nicotinic receptor blocker hexamethonium. Similarly, the arachidonic acid- or norepinephrine induced 6-keto-PGF1 alpha accumulation was not altered by these muscarinic receptor antagonists. Indomethacin, a cyclooxygenase inhibitor, prevented arachidonic acid, ACh- or APE induced 6-keto-PGF1 alpha output. Removal of the endothelium abolished the production of 6-keto-PGF1 alpha elicited by ACh, APE, bradykinin, and calcium ionophore A 23187, but not that induced by angiotensin II, K+ or norepinephrine. These data suggest that vascular prostaglandin generation elicited by cholinergic agonists is mediated via activation of M2 alpha and M2 beta but not M1 muscarinic receptors, which are most likely located on the endothelium. PMID- 2111036 TI - Irradiation of rats abolishes susceptibility of PGI2 synthesis in blood vessels to peroxidative agents. AB - Thoracic and abdominal aortas were obtained from rats after irradiation and used for the estimation of the synthesis of prostacyclin (PGI2) determined as 6-keto PGF1 alpha. Twenty four h after exposure to 7.0 Gy an increase was noted in the amount of PGI2 released, and 4 weeks later its level significantly decreased. The 24 h value did not increase with the further radiation dose increment (9, 12.5, 15 Gy). Cysteine or H2O2 intensified prostacyclin synthesis in control vessels but decreased it in vessels from the animals irradiated 24 h earlier. Later after the exposure cysteine or H2O2 were no longer effective. PMID- 2111037 TI - [Midazolam: pharmacologic and clinical aspects]. PMID- 2111038 TI - [Viewpoint. Hepatitis C]. PMID- 2111039 TI - Long-term preservation of blood samples for diagnosis of Trypanosoma cruzi infection. AB - Feasability and suitability for field research of a whole-blood preservation method was evaluated through the screening of anti-Trypanosoma cruzi antibodies in 1209 samples under different conditions. Antibody reactivity of paired samples from preserved capillary blood (CBP) and sera from venous blood (VBS) were studied by specific techniques. Over 96% concordance was found on indoor studies carried out with samples without storage or after 15 or 30 days preservation of CBP at 37 degrees C and VBS at -20 degrees C. Outdoor studies performed at field conditions, achieved a 92.1% concordance. PMID- 2111040 TI - [Ossification of the ligamentum flavum at the thoracolumbar junction. Role of rotatory strains]. PMID- 2111041 TI - [Ossifying periostitis of the fibula disclosing SAPHO syndrome]. PMID- 2111043 TI - Ileal diverticulosis in a black patient. A case report. AB - A 54-year-old black man presented to hospital with diarrhoea containing blood and mucus and marked loss of weight over a 1-year period. Barium enema examination revealed cobblestoning and rose-thorn ulceration with possible stricture formation of the terminal ileum. A right hemicolectomy was performed to remove inflamed sections of small and large bowel. Histological examination of the resected specimen demonstrated features of ileal diverticular disease. This is the first documented case of this disease occurring in a black patient. PMID- 2111042 TI - Thromboplastin activity of blood monocytes after total hip replacement. AB - Thromboplastin activity of monocytes from blood of seven patients with total hip replacement was investigated. At 24 h and 48 h after surgery, thromboplastin activity was significantly increased compared to the activity before surgery. Thromboplastin activity of endotoxin-stimulated monocytes was significantly increased at 24 h after surgery. There were no significant changes in Factor V after surgery, Factor VII was significantly lowered at 24 h after surgery, while Factor VIII and fibrinogen were significantly increased at 72 h after surgery. The results indicate that monocyte thromboplastin may be a thrombogenic factor after total hip replacement surgery. PMID- 2111044 TI - Teratogenic effects on the neuroepithelium of the CD-1 mouse embryo exposed in utero to sodium valproate. AB - A causal association has now been recognized between the use of the anticonvulsant drug sodium valproate during pregnancy and the increased incidence of spina bifida in the human population. The objective of this study was to investigate the teratogenic effects of sodium valproate on the cephalic 1) neuroepithelium, 2) extracellular matrix, and 3) embryonic protein content in the CD-1 mouse embryo. Nulliparous female CD-1 mice were dosed intraperitoneally on day 8 of gestation with 340 mg/kg of sodium valproate. On day 10 of gestation, females were killed by cervical dislocation, and all live embryos were assigned to one of the following groups and processed accordingly for: 1) head measurements, 2) scanning electron microscopy, 3) total protein determination, 4) two-dimensional polyacrylamide gel electrophoresis, 5) immunohistochemistry, and 6) light microscopy. Exposure to sodium valproate at the selected dosage resulted in a 30% incidence of neural tube defects in the cranial region of these embryos. Treated embryos showed a significant reduction in head size, indicating a drug induced microcephaly. No major differences were seen in the total embryonic protein patterns between control and treated embryos. Immunoreactivity to laminin and fibronectin showed a similar distribution in control and treated embryos except in the vasculature pattern of the hindbrain neuroepithelium. The neuroepithelium of the treated embryos showed marked disorganization when it was examined histologically, particularly in the forebrain region. Cells were disoriented, and there was a noticeable loss of intercellular adhesion in the juxtaluminal region. Increased cellular blebbing was apparent at the ependymal surface, and large protrusions of cells were seen invading the neural tube lumen. The lumen was distorted in shape and frequently contained blood cells. Irregularities and gaps were observed in the underlying basal lamina. These results suggest that treatment with sodium valproate during a critical time in neurogenesis in the CD-1 mouse embryo alters the normal architecture of the neuroepithelium, with a loss of integrity at both the basal and apical surfaces. The alterations seen in the neuroepithelium at any of these sites in this animal model could help explain the increased incidence of spina bifida seen in children of epileptic mothers receiving sodium valproate. PMID- 2111045 TI - On the properties of the international standards for tissue plasminogen activator. PMID- 2111046 TI - The effect of combined factor XI deficiency with von Willebrand factor abnormalities on haemorrhagic diathesis. AB - To account for the lack of correlation between the level of factor XI (FXI) in deficient patients and haemorrhagic manifestations, we correlated the prevalence of combined FXI and von Willebrand's factor (vWF) deficiency in 212 FXI-deficient patients. Fifty-four patients had a combined FXI and vWF deficiency: 16 patients had severe and 38 patients had mild FXI deficiency. In a group of 28 patients with comparably mild FXI deficiency, 14 bleeders had significantly lower mean vWF, Ag, ristocetin cofactor and ristocetin induced platelet aggregation than 14 non-bleeders selected on the basis of comparable FXI levels. These findings suggest that the combination of FXI and vWF deficiency is common and may affect the bleeding tendency in mild FXI deficiency. PMID- 2111047 TI - Effects of an antifibrin monoclonal antibody and fragments thereof on some properties of fibrin. AB - Antifibrin monoclonal antibody Y22, of IgG1-subclass, has its epitope in the D domain of fibrin. In a thrombin time assay, Y22 and its F(ab)2 fragments interfere with clotting of citrated plasma. Transmission and scanning electronmicroscopic studies show that clotting of citrated blood or plasma in the presence of Y22 results in formation of thin, short fibrin fibres. The (smaller) Fab fragments of Y22 did not have an anti-clotting effect. This suggests that the anticoagulant effect of Y22 is due to steric hindrance of the association of fibrin monomers. A control antibody and its F(ab)2 and Fab fragments have no effect on fibrin formation. In a parabolic rate assay, Y22 Fab fragments interfered strongly with the fibrin-induced enhancement of the t-PA-catalyzed plasminogen activation, whereas intact Y22 and a control antibody did not. In contrast with their effects on the fibrin assembly, the effects of Y22, Y22 F(ab)2 and Y22-Fab on the capacity of fibrin to act as a rate-enhancer in the plasminogen activation by t-PA appears to decrease with the size of the immunoreactive entity. As is discussed, this may be due to the differential accessibility of sites involved in stimulation and polymerization which are located in the fibrin D-domain. PMID- 2111048 TI - Fibrin affinity and clearance of t-PA deletion and substitution analogues. AB - To investigate structure-function relationships in tissue-type plasminogen activator (t-PA) we deleted the following domains in the heavy chain: a) The epidermal growth factor domain (t-PA del. G), b) the finger domain, and the epidermal growth factor domain (t-PA del. FG), and c) the finger, the epidermal growth factor and Kringle 1 (t-PA del. FGK1). To study specifically the function of the growth factor domain we made two substitutions of d) 8 amino acids (consensus sequence) in the growth factor domain (t-PA G-CS) and e) the whole domain with factor IX growth factor domain (t-PA G-IX). Finally, f) an analogue with substitution in the finger domain (fibronectin consensus sequence) was constructed (t-PA F-CS). A reduced fibrin binding of all the analogues was found. The fibrin stimulated activity of all analogues was also reduced and correlated to the fibrin binding. In contrast, the activity of the analogues in the clot lysis assay and the plate assay were only slightly reduced as compared to authentic t-PA. This suggested that at high fibrin concentrations the decreased fibrin affinity was less critical for obtaining a high fibrinolytic activity. All analogues had a prolonged half-life in vivo as compared to authentic t-PA. The assumption of clearance mechanism involving mainly the growth factor region (or Kringle 1) was not challenged by the observation of a prolonged half-life for the substitution analogue t-PA F-CS.2+off PMID- 2111049 TI - Different tissue plasminogen activator release in the arm and leg during venous occlusion is equalized after DDAVP infusion. AB - The mechanism of tissue plasminogen activator (t-PA) release during arm and leg venous occlusions and DDAVP (1-desamino-8-D-arginine vasopressin) infusion was studied in 10 healthy males. The following determinations were carried out on venous blood: t-PA antigen (ELISA), t-PA activity, and t-PA inhibitor (PAI) activity (amidolytic assays). Before DDAVP, there was a 270% t-PA antigen increase in the arm at the end of occlusion as opposed to only a 40% increase in the leg. After DDAVP, t-PA antigen at the end of arm and leg occlusion reached an equal level which was significantly higher than in the arm before DDAVP. The study produced no evidence of PAI release during venous occlusion of a limb. It is concluded that DDAVP is able to elicit t-PA release from arm as well as from leg vessels. The poor fibrinolytic response of leg vessels to venous occlusion is not due to a high PAI release or t-PA stores depletion in leg vessels, but rather to low basal t-PA release in leg vessels. PMID- 2111050 TI - A plasma clot lysis assay based on the release of fibrin degradation products: application to the diagnosis of hypofibrinolytic states. AB - Using a monoclonal antibody-based assay, we measured the fibrin degradation product release in the supernatant of plasma clots obtained before and after venous occlusion (VO) in 30 patients with definite or suspected vascular thrombosis (19 definite and 2 suspected deep vein thrombosis, 6 recurrent superficial thrombophlebitis, 3 arterial occlusions of lower limbs). tPA and PAI 1 concentrations were determined using ELISA assays; the post-occlusion values were corrected for haemoconcentration. The increase in tPA during VO was correlated with haemoconcentration (r = 0.74), but 3 patients had ineffective VO (less than 2% increase in proteins). The fibrinolytic response to VO was evaluated using the shortening of the time necessary for the release of 200 micrograms of fibrin degradation products per mg of fibrinogen (delta T 200). Two among the 27 patients with effective VO were bad responders with a delta T 200 less than 3 h (whereas all the others had delta T 200 greater than 10 h). These patients had respectively a deficient tPA release (delta tPA = 1 ng/ml) and an elevated PAI-1 level at rest (33 ng/ml). Several other patients were bad responders in terms of tPA release or of shortening of the euglobulin clot lysis time but they had a normal delta T 200. This plasma clot test reflects the ability of free tPA to bind to fibrin (the amount of which depends on the level of tPA and PAI-1), and may be useful in the diagnosis of a hypofibrinolytic state. PMID- 2111051 TI - Relationships between euglobulin clot lysis time and the plasma levels of tissue plasminogen activator and plasminogen activator inhibitor 1. AB - The relationships between tissue plasminogen activator (tPA), its fast acting inhibitor (PAI-1) and euglobulin clot lysis time (ELT) were investigated with healthy volunteers' plasma. Turbidimetric clot lysis assay by the microtiter plate reader was utilized for ELT with a slight modification. Both tPA and PAI-1 showed the significant correlation with ELT. tPA had a significantly positive, not negative, correlation with ELT (R = 0.387, p less than 0.001). Higher correlation coefficients (R = 0.580, p less than 0.001 and R = 0.599, p less than 0.001) were obtained between ELT and total PAI-1 or free PAI-1 than tPA or tPA PAI-1 complex (R = 0.427, p less than 0.001). The positive correlation was also obtained between tPA and PAI-1. These data suggest that PAI-1 is a highly important factor for ELT, especially, the amounts of free PAI-1 being the key factor to determine the ELT, which can represent the potential activity of the fibrinolytic system. PMID- 2111052 TI - Decreased prostaglandin-I2 stability in acute myocardial infarction. AB - It has been demonstrated that under certain conditions the in-vitro half-life of biologically active PGI2 in plasma is extremely shortened, which may result in vivo in a local haemostatic imbalance. In 36 patients suffering from acute myocardial infarction a sequential change in in-vitro half-life of synthetic PGI2 was therefore studied during 3 weeks. 21 patients admitted turning out not to develop myocardial infarction served as follow-up controls. During and shortly after the acute episode the plasmatic half-life of PGI2 in-vitro was shortened by about 40%, improving continuously thereafter. No certain influence of either risk factors, sex or age could be discovered. A possible influence of various drugs administered in the hospital period has been excluded in 43 patients with proven coronary artery disease. No such changes occurred during acute angina pectoris attack in 12 patients. It remains to be established, whether the short-lasting destabilisation of PGI2 may be an acute disease-associated finding, or an important pathogenetic factor. PMID- 2111053 TI - [Chronic non-A non-B hepatitis treated with interferon]. AB - Non-A non-B hepatitis remains a diagnostic and therapeutic problem. Recently published data indicate that interferon may represent a considerable step forward in the therapy of this disease. We have treated a patient with non-A non-B hepatitis with recombinant interferon alpha 2-B. Both biochemical and morphological liver parameters were normalized after nine months of treatment. Further studies are being performed to establish the efficacy and effective doses of interferon in the treatment of non-A non-B hepatitis. PMID- 2111054 TI - Isolation and identification of a pyrrolic glutathione conjugate metabolite of the pyrrolizidine alkaloid monocrotaline. AB - This report describes the isolation and identification of a monocrotaline derived, glutathione-conjugated pyrrole obtained from the bile of male Sprague Dawley rats. Bile obtained from rats given an intravenous bolus of 14C monocrotaline was fractionated using a series of chromatographic separations. Initial purification with cholestyramine resin removed bile acid and pigment contaminants. Subsequent anion exchange and reversed-phase HPLC separations yielded several fractions that contained the 14C label and tested positive for pyrroles using Ehrlich's reagent. These fractions were analyzed using fast-atom bombardment tandem mass spectrometry (FAB MS/MS). In addition to glutathione conjugated dehydroretronecine, at least one other pyrrole present had similar ionic properties. The latter was not present in amounts sufficient for positive identification. PMID- 2111055 TI - Positive and negative effects of diagnostic intensities of ultrasound on erythrocyte blood group markers. AB - Human erythrocytes were exposed in vitro to diagnostic intensities of ultrasound. Various antigenic tests were conducted to see if the different blood group markers had been changed. No change was observed following sonication for Ss, M, K1, ABO, and the rhesus factors. However a marked reduction was found for the N antigen when assayed using the lectin isolated from Vicia graminea. Several experiments were performed to ensure that this effect was not an artefact. If the cells were not resuspended in fresh medium immediately following sonicating then the magnitude of the effect rapidly decreased. We were unable to detect free N antigen in the supernatants from the sonicated cell suspensions. We were also unable to demonstrate changes in the level of the N antigen following sonication if we used anti-N sera from rabbits. A surprising observation was that different batches of the lectin preparation from the same manufacturer could eliminate the effect. PMID- 2111056 TI - Survey for Breda virus in neonatal calf diarrhoea. PMID- 2111057 TI - Immunopathology of experimental Brucella abortus strain 19 infection of the genitalia of bulls. AB - Antibody responses in serum and semen, and immunoglobulin containing cell (ICC) populations in the genitalia of bulls were compared after inoculating Brucella abortus strain 19 into the seminal vesicles of two bulls (ISV route) and into testes in two other bulls (IT route). Bulls seroconverted as early as 1 week post infection (PI). Peak serum titres as determined by the serum agglutination test (SAT), complement fixation test (CFT) and ELISA occurred at PI weeks 3, 4 and 5 respectively. Highest titres were in IT inoculated bulls. Seminal antibodies against B. arbotus S19 were demonstrated from 2 weeks PI by both the SAT and the Rose Bengal Test (RBT) and highest titres occurred at PI weeks 3 and 4. Examination of immunoglobulins (Ig) in semen, however, revealed no significant differences of Ig isotypes between infected and control animals at any examination time. When bulls were killed at 7 weeks PI, quantitation of ICC in genital sections stained by the peroxidase-anti-peroxidase method revealed an overwhelming predominance of IgG containing cells in inflamed organs. In all cases IgG1- and IgG2-containing cells were prevalent, and present in approximately equal numbers. IgA-containing cells were second in prevalence in inflamed tissues while IgM cells were always in low percentage. High prevalence of ICC in infected genitalia, associated with elevated specific seminal antibodies but not with increased seminal Ig indicates that most Ig remains localised in tissues and is not transferred into genital secretions. PMID- 2111058 TI - The serological response of cattle immunized with Yersinia enterocolitica O:9 or O:16 to Yersinia and Brucella abortus antigens in enzyme immunoassays. AB - Sera from calves immunized with Yersinia enterocolitica serotypes O:9 or O:16 were tested by indirect enzyme linked immunosorbent assay (ELISA) using lipopolysaccharide (LPS) preparations from Brucella abortus or Y. enterocolitica O:9 or O:16 for their antibody content of the IgG1 or IgG2 subclasses. High IgG1 responses were present with the three antigens in both groups although some individual variations between animals were noted. The IgG2 responses were modest and in some cases not above background 'noise'. Thus IgG2 antibody was not measurable in sera from serotype O:9 injected calves when using serotype O:16 LPS or in serotype O:16 injected calves when using B. abortus or serotype O:9 LPSs. A competitive ELISA using B. abortus O-polysaccharide and a monoclonal antibody to B. abortus LPS (initially designed to differentiate the antibody responses of cattle naturally infected with B. abortus from those vaccinated with strain 19) was used on sera from both groups of calves. Using this test, no antibody was detected in the group immunized with serotype O:16 and except for one animal in the serotype O:9 immunized group, only low levels of antibody were transiently in evidence. One animal in this group responded with quite high levels of competing antibody which, however, declined towards the end of the test period. The competitive ELISA may prove a useful serological tool for differentiating vaccinal and field infection titers to B. abortus and also to eliminate cross reactions observed with Y. enterocolitica serotypes. PMID- 2111059 TI - Human monoclonal anti-D with reactivity against category DVI cells used in blood grouping and determination of the incidence of the category DVI phenotype in the DU population. AB - B-lymphoblastoid cell lines transformed by Epstein-Barr virus were produced from cells obtained from a hyperimmunised donor with serum anti-D activity against category DVI red cells and enriched for this activity by rosetting with category DVI red cells. Three clones produced IgG1 anti-D and had stable cell growth and continuous secretion of antibody in prolonged culture. The monoclonal antibodies reacted with category DVI red cells, when assessed manually and in an automated blood grouping system, and are useful blood grouping reagents for the detection of the category DVI phenotype. Using a radiometric technique, the number of antibody molecules bound to category DVI red cells from 5 individuals was estimated to range from 2,800 to 11,200 per cell. Five percent of blood donors classed as Du in the south western region were found to have the category DVI phenotype. PMID- 2111060 TI - HIV seroconversion in haemophilic boys receiving heat-treated factor VIII concentrate. PMID- 2111061 TI - A rare case of Rh immunization. PMID- 2111062 TI - Nomenclature for factors of the HLA system, 1989. PMID- 2111064 TI - Studies in red blood cell preservation. 3. A phosphate-ammonium-adenine additive solution. AB - The maintenance of adenosine triphosphate (ATP) in red blood cells (RBC) during storage is largely dependent on the integrity of glycolytic metabolism in the Embden-Meyerhof pathway. Meryman et al. [Transfusion 1986; 26:500-505] hypothesized that a solution that increased the surface tension of the corpuscles through hypotonic swelling might retard the development of echinocytosis and membrane loss by the shedding of exocytic vesicles. Unexpectedly, maintenance of good ATP levels and satisfactory RBC survivals were found for a long as 18 weeks. The purpose of our study was to test their observations and to explore the possible mechanisms. Equal parts of units of packed RBC were stored in the experimental preservative and, for comparison, in ADSOL. The most notable findings were ATP values at 4 weeks averaging 5.2 mumol/g Hb (130% of initial) and at 12 weeks 2.9 mumol/g Hb (73% of initial), whereas these values declined as expected in ADSOL. Mean RBC diameters and surface areas by morphometric analysis were not significantly different in the two preservatives indicating the absence of any hypotonic swelling. The morphology scores of the RBC were significantly better throughout (p less than 0.05) than in ADSOL. The shedding of exocytic hemoglobin-containing vesicles was essentially the same in both preservatives. Our data confirm the observation that ATP levels are well maintained for at least 12 weeks, but do not show any evidence that hypotonic swelling was a part of the mechanism. PMID- 2111063 TI - Studies in red blood cell preservation. 2. Comparison of vesicle formation, morphology, and membrane lipids during storage in AS-1 and CPDA-1. AB - The changes in morphology, the quantitative changes in membrane lipids and the shedding of exocytic vesicles by red blood cells (RBC) stored for 42 and 56 days in AS-1 and CPDA-1 were compared. RBC stored in AS-1 shed significantly less vesicle membrane cholesterol, phospholipid and protein and maintained better morphology scores. RBC membrane cholesterol remained higher after 56 days in AS-1 than in CPDA-1. The data suggest that during the first weeks of storage cholesterol is lost from the RBC membrane followed by a larger release of phospholipids accompanied by alterations in the phosphoinositides. The shedding of exocytic vesicles appears to be secondary to the changes in morphology resulting from the perturbation of the membrane lipids. PMID- 2111065 TI - Anti-hepatitis C antibodies in prospectively followed-up transfused patients. PMID- 2111066 TI - Testing efficacy of anti-D sera by a panel of donor red cells with weak reacting D antigen and with partial D antigens. PMID- 2111067 TI - International round table conference on the definition of the Rh-negative blood donor. PMID- 2111068 TI - [The clinical characteristics of peripheral nerve tumors]. AB - The authors present an analysis of the clinical course of different kinds of tumours of the peripheral nerves in 74 patients. In 61 patients the tumours were benign and in 13 patients they were malignant. The tumours were located at different levels of the nerve trunks of the extremities and neck. PMID- 2111069 TI - [Contact allergies to CN and CS ("tear gas") in participants in demonstrations]. AB - 56 occasional demonstrators were interviewed with regard to former skin contact with omega-chloroacetophenone (CN) or ortho-chlorobenzylidene malononitrile (CS). 33 persons (59%) reported skin reactions of various kinds. Patch testing with CN, the structurally related preservative chloroacetamide, and CS revealed clinically relevant reactions to CN in 3 cases and questionable positive reaction to CS in one case. 8 further patients showed mild reactions to CN and CS. We did not find any indication of cross reactions between CN and chloroacetamide. PMID- 2111070 TI - Sleep and sleep deprived EEG in partial and generalized epilepsy. AB - Sleep and sleep deprivation are often used for EEG activation in epilepsy. We compared postprandial naps and day-long sleep deprived EEGs in 36 patients with generalized seizures, 57 complex partial seizure patients, and 7 individuals with mixed seizure disorders. Ten of 36 generalized seizure patients had normal sleep and sleep deprived EEGs, while both were normal in 16 of 57 partial seizure patients. Both were abnormal in 18 of 36 generalized and 22 of 57 partial epileptics. Seven generalized seizure patients had epileptiform discharges or seizures during afternoon naps but normal sleep deprived EEGs. No partial seizure patients had normal sleep deprived EEGs and abnormal nap, but 29 of 57 had abnormalities or seizures only with sleep deprivation. All 7 mixed seizure patients had abnormal sleep and sleep deprived studies, and 6 had seizures, 4 on both studies. Natural sleep may facilitate the appearance of generalized seizures or epilepti-form discharges, while sleep deprivation may accentuate the yield of EEG abnormality in partial epilepsy. Either is likely to be abnormal in patients with mixed seizures and encephalopathy. Natural sleep and sleep deprived EEGs are an appropriate combination in the evaluation of refractory seizures. PMID- 2111071 TI - Rhinocerebral mucormycosis and internal carotid artery thrombosis in a previously healthy patient. AB - Mucormycosis is a very serious fungal infection caused by habitual saprophytes of the human organism, in many cases concomitant with various pathological conditions marked by immunodepression. The rhinocerebral variant habitually accompanies ketoacidotic diabetes. We report a case of rhinocerebral mucormycosis in a subject free from immunodepression and non-diabetic, in apparently normal health. Following treatment with amphotericin B combined with 5-fluorocytosine and surgery, remission of the disease was finally secured and about one year after the last operation there are no sign of resumption. PMID- 2111072 TI - [Homage to Mr. Ludo van Bogaert]. PMID- 2111073 TI - Amino acid disturbances in the neuronal environment--cause or consequence in human epilepsy. PMID- 2111074 TI - Phosphorylated high molecular weight neurofilament protein in lower motor neurons in amyotrophic lateral sclerosis and other neurodegenerative diseases involving ventral horn cells. AB - Lower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis (ALS), Werdnig-Hoffmann's disease (WH), X-linked recessive bulbospinal neuronopathy (X-BSNP) and multiple system atrophy (MSA), all of which were known to involve the lower motor neurons, were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments. The incidence of Ta-51-positive neurons was significantly increased in ALS, WH and MSA, but not in X-BSNP. Ta-51 positive neurons showed a wide variety of morphological appearances, including neurons with normal appearance, central chromatolysis, simple atrophy and neurons containing massive neurofilamentous accumulation. In aged-control cases, similar Ta-51-positive neurons were observed, although to a much lesser extent. In ALS, spheroids and globules, which were strongly positive for Ta-51, were also significantly increased. Ta-51-positive motor neurons, spheroids and globules appeared in proportional to the number of remaining large motor neurons in ALS. PMID- 2111075 TI - Effects of arachidonic acid and prostaglandin F2 alpha in isolated rat lungs. AB - Isolated rat lungs were ventilated and perfused by saline-Ficoll perfusate at a constant flow. The baseline perfusion pressure (PAP) correlated with the concentration of 6-keto-PGF1 alpha the stable metabolite of PGI2 (r = 0.83) and with the 6-keto-PGF1 alpha/TXB2 ratio (r = 0.82). A bolus of 10 micrograms exogenous arachidonic acid (AA) injected into the arterial cannula of the isolated lungs caused significant decrease in pulmonary vascular resistance (PVR) which was followed by a progressive increase of PVR and edema formation. Changes in perfusion pressure induced by AA injection also correlated with concentrations of the stable metabolites (6-keto-PGF1 alpha: r = -0.77, TxB2: -0.76), and their ratio: (6-keto-PGF1 alpha/TXB2: r = -0.73). Injection of 10 and 100 micrograms of PGF2 alpha into the pulmonary artery stimulated the dose-dependent production of TXB2 and 6-keto-PGF1 alpha. No significant correlations were found between the perfusion pressure (PAP) which was increased by the PGF2 alpha and the concentrations of the former stable metabolites. The results show that AA has a biphasic effect on the isolated lung vasculature even in low dose. The most potent vasoactive metabolites of cyclooxygenase, prostacyclin and thromboxane A2 influence substantially not only the basal but also the increased tone of the pulmonary vessels. PMID- 2111076 TI - Effect of gonadotropin (FSH-LH) and thyrotropin (TSH) treatment in adolescence on TSH-sensitivity in adult rats. AB - Hormonal imprinting is characteristic of the neonatal age, in which the receptor of the target cell matures, i.e. acquires its adult binding capacity, and cellular response becomes established in presence of the adequate hormone. The normal course of imprinting may be altered by certain molecules (related hormones, hormone analogons) which are able to bind to the receptor of the adequate hormone. The chemically related gonadotropic and thyrotropic hormones may overlap on each other's receptors not only in the perinatal age, but also in the early adulthood, and this overlap of the binding may give rise to an imprinting-like effect. An example of this phenomenon was observed in the present study, in which rats of seven weeks of age treated with gonadotropin showed a significant decrease in thyroidic response to TSH, and exposure to TSH failed to increase their basic thyroxine concentration to the normal (control) level. This depressive effect of gonadotropin was slightly reduced in the presence of LPS (endotoxin), causing membrane perturbation, while pretreatment with LPS and TSH accounted for an increased sensitivity to TSH in later phases of the rat's life. These experimental observations support the possibility of a special form of imprinting in adolescence. PMID- 2111077 TI - Ventricular histamine concentrations and mast cell counts in the rat heart during acute ischaemia. AB - The ventricular histamine concentrations and mast cell counts of naive and disodium cromoglycate-treated rats subjected to acute left coronary artery ligation under pentobarbitone anaesthesia were examined. In naive animals, there was a significant increase in the right ventricular histamine level at 2 min following left coronary artery ligation. Left ventricular histamine concentrations tended to decrease, and were significantly lower than those of the right ventricle at 5 min. However there were no significant changes in mast cell counts of the right or left ventricles after left coronary artery ligation. Treatment with disodium cromoglycate did not significantly alter the ventricular mast cell counts, interfere with the changes in ventricular histamine concentrations, or the occurrence of early ventricular arrhythmias and haemodynamic changes in response to acute left coronary artery ligation. It is suggested that the increase in the right and decrease in the left ventricular histamine concentrations during acute myocardial ischaemia involves mainly the non-mast cell stores, instead of mast cell sources, of cardiac histamine. PMID- 2111078 TI - Estrogenic regulation of diamine oxidase activity in rat uterus. AB - Diamine oxidase activity was studied in female rat tissues during the estrous cycle and after 17 beta-estradiol administration. During the estrous cycle, uterine and hepatic enzyme activities were highest at proestrus and lowest at estrus, when estrogen plasma levels are known to be respectively high and low. The administration of 17 beta-estradiol to ovariectomized rats caused a rapid and prolonged increase in enzyme activity in uterus and only a transient increase in the liver. Such increases were prevented by cycloheximide and by actinomycin D administration. No changes were observed in renal enzyme activity during estrus or after hormone treatment. Our data suggest that estrogens regulate diamine oxidase activity in rat uterus by a mechanism of enzyme induction. PMID- 2111079 TI - Modification by some antagonists of the shape changes of venous endothelial cells in response to inflammatory agents in vitro. AB - Endothelial cells lining guinea pig inferior venae cavae change shape when exposed to histamine, bradykinin, A23187 or platelet-activating factor (PAF) in vitro. Pre-treatment of the endothelium with isoprenaline or quin 2 significantly reduced the shape changes produced in response to histamine, bradykinin and A23187, but not those to PAF. Since both isoprenaline and quin 2 may reduce the concentration of cytoplasmic Ca++, the former by raising cyclic AMP (cAMP) levels and the latter by acting as a Ca++ buffer, the results provide further evidence for the involvement of Ca++ in the responses of large vein endothelial cells to inflammatory agents in vitro. The effects of pre-treating the endothelium with the histamine receptor-blockers mepyramine (H1) or cimetidine (H2), or the bradykinin receptor-blockers des-arg9[leu8] bradykinin (B1) or des-arg[Hyp3, Thi5,8,D-Phe7] bradykinin (B2) suggest that the response to histamine is both H1 and H2 receptor-mediated, while the response to bradykinin is only B2 receptor mediated. PMID- 2111081 TI - Silibinin (Legalon-70) enhances the motility of human neutrophils immobilized by formyl-tripeptide, calcium ionophore, lymphokine and by normal human serum. AB - Experiments reported here were designed to investigate the effect of silibinin (extracted from Silybum marianum) on human polymorphonuclear leukocyte (PMN) motility and on leukocyte immobilizing activity of lymphokine (leukocyte inhibitory factor, LIF), formyl-Met-Leu-Phe (fMLP), calcium ionophore A-23187 and human sera inactivated by heat (HI-S). In the in vitro experiments, silibinin (1 10 micrograms/ml) failed to influence the random motility of unstimulated PMNS in agarose droplet assay, but enhanced the motility of the PMNs immobilized by fMLP, calcium ionophore, LIF or by autologous human sera. In the in vivo study, silibinin (Legalon-70) two hours after the administration was effective in enhancing spontaneous motility of leukocytes obtained from health volunteers which action could be regarded as a consequence of the decrease of leukocyte immobilizing activity being present in normal human plasma. PMID- 2111080 TI - Inhibition of human periodontal prostaglandin E2 synthesis with selected agents. AB - Considerable evidence has demonstrated the importance of PGE2 synthesis in the pathogenesis of periodontal disease. Although various cyclooxygenase inhibitors have been known to block periodontal PGE2 synthesis and prevent disease progression in animal models, there are few reports comparing relative efficacies of various inhibitors of arachidonic acid (ARA) metabolism. We have developed a sensitive in vitro assay to measure PGE2 synthesis in periodontal tissues. The apparent IC50 values (i.e. the concentration of drug which causes 50% inhibition of maximum PGE2 synthesis) have been determined for a series of arachidonic acid analogues as well as competitive and non-competitive cyclooxygenase inhibitors. Periodontal tissue homogenates were incubated in the presence of 3H-arachidonic acid for 45 min at 37 degrees C. Inhibitors were tested at 10(-10)-10(-4) M and at zero concentration to measure conversion of 3H-arachidonate to 3H-PGE2. Log or half log dilutions of inhibitors were tested in triplicate for each assay. Radiolabeled PGE2 was extracted from homogenates, purified by reverse phase chromatography and quantitated by double antibody capture. RIA was performed on each homogenate to determine the amount of endogenous unlabeled PGE2 present in the sample to correct for antibody capture recovery. The apparent IC50 values were determined for each drug by averaging two or more replicate assays. Specific total enzymatic activity of periodontal tissue homogenates was typically 5-11 pg PGE2/min/mg tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111082 TI - A glycerol ether induces mobilization and 12-lipoxygenation of arachidonic acid in macrophages. Synergistic effect on mobilization and induction of leukotriene C formation by activators of protein kinase C. AB - A glycerol triether, 1,2-isopropylidene 3-0-decanyl-sn-glycerol, was found to induce mobilization of arachidonic acid from ethanolamine phosphoglycerides and phosphatidylinositol in mouse peritoneal macrophages. This effect showed structural specificity, occurred without activation of protein kinase C and resulted in formation and release of predominantly 12-hydroxy-eicosatetraenoic acid. Activators of kinase C (4-beta-phorbol 12-myristate 13-acetate and 1,2 dioctanoyl-sn-glycerol) instead specifically enhance prostaglandin E2 formation. When macrophages were exposed to both a kinase C activator and the glycerol triether, the mobilization of arachidonic acid was synergistically enhanced and formation of leukotriene C was induced. PMID- 2111083 TI - The influence of histamine and PGE2-induced hyperaemia and oedema on respiratory metabolism in normal human forearm skin. AB - Transcutaneous measurements of pO2 and pCO2 were made on the forearm skin after intradermal injection of histamine, PGE2, and saline. The mediators, used at concentrations which induce intense hyperaemia, did not modify the steady state tcpO2/pCO2 levels measured with a sensor head temperature of 44 degrees C when breathing air or hyperbaric (2ATA) oxygen. It was deduced that gas transport is unaffected by mediator-induced conditions in the skin. The rates of fall of tcpO2 and of rise of tcpCO2 after arresting the forearm circulation by cuff occlusion of the arm were significantly less at the histamine site than at the PGE2 and saline sites. The values over the PGE2 and saline injection sites were less than those over undisturbed skin. The dynamic tests of respiratory gas exchange indicate that the skin metabolic rate is reduced at all injection sites and the greatest effect was seen with histamine. Measurement of dermal thickness after saline injection has shown that the excess interstitial fluid persists at the time of maximal hyperaemia: this is further accentuated at the histamine site through active oedema formation. Accumulation of excess interstitial fluid (persistence of aqueous injection or oedema generated by the action of mediator) separates the tissue cells. The reduction in the number of cells per unit volume is sufficient to explain the observed reduction in oxygen consumption per unit volume of skin. It is concluded that the increased diffusional distances in mediator-induced oedema are unimportant for the respiration of otherwise normal tissues, but that oedema by reducing oxygen flux may contribute appreciably to the hypoxia of inflamed tissue infiltrated with metabolically active cells. PMID- 2111084 TI - Antiplatelet constituents of garlic and onion. AB - We have identified three main antiplatelet constituents, namely adenosine, allicin and paraffinic polysulfides in both garlic and onion. Adenosine and allicin both inhibited platelet aggregation without affecting cyclooxygenase and lipoxygenase metabolites of arachidonic acid. The trisulfides inhibited platelet aggregation as well as thromboxane synthesis along with induction of new lipoxygenase metabolites. The data indicate that the observed in vivo antiplatelet effects of ingesting onion and garlic are attributable more to the adenosine than to the allicin and paraffinic polysulfide constituents. PMID- 2111086 TI - Branhamella catarrhalis: a microbiologic and clinical update. Proceedings of a symposium. Houston, Texas, September 15, 1989. PMID- 2111085 TI - The coumarin derivative AD6 inhibits the release of arachidonic acid by interfering with phospholipase A2 activity in human platelets stimulated with thrombin. AB - AD6 is a coumarin derivative which is able to inhibit platelet aggregation and release due to various agonists as adrenaline, PAF, Ca++ ionophore and others. It has been demonstrated that this compound reduces the production of free arachidonate and diglyceride from human platelets pulse-labeled with radioactive arachidonic acid thus suggesting a possible interference with the activity of phospholipase A2 and/or phospholipase C. The present report indicates that the drug has no effect on the increase of the labeling of phosphatidic acid which takes place when platelets pulse-labeled with arachidonic acid are stimulated with thrombin. Furthermore, AD6 is not able to cause changes on the metabolism of phosphoinositides monitored using platelets pre-labeled with [3H] inositol. These observations exclude the possibility that AD6 interferes with phospholipase C activity. Experiments with platelets pulse-labeled with arachidonate suggest that AD6 inhibits phospholipase(s) A2 activity or modulate negatively one or more processes involved in its activation. PMID- 2111087 TI - Spectrum of disease due to Branhamella catarrhalis in children with particular reference to acute otitis media. AB - For many years Branhamella catarrhalis was regarded as a non-pathogenic inhabitant of the respiratory tract. This article outlines the spectrum of B. catarrhalis disease in childhood and the extent of the evidence for a pathogenic role of the organism. B. catarrhalis is a rare etiologic agent in septicemia, meningitis, and other systemic illness in both apparently normal and immunocompromised infants and children. It is an unusual cause of ophthalmia neonatorum, but can be confused with Neisseria gonorrhoeae. Whether or not B. catarrhalis is acquired from the birth canal in these cases has not been established. B. catarrhalis is most common as a respiratory tract pathogen in children, including pneumonia, bacterial tracheitis, sinusitis, and otitis media. Since it is difficult to rigorously document pathogenicity of any bacterium in bronchopulmonary infections in children, it is probable that the spectrum of B. catarrhalis disease is wider than that reported to date. The evidence for pathogenicity in acute otitis media is more extensive than for other infections. Otitis media due to B. catarrhalis is clinically similar to that due to other pathogens. B. catarrhalis can be isolated in pure culture from the middle ear exudate and persists if there is no antibacterial treatment. Gram-negative intracellular and extracellular diplococci can be seen on smears of the inflammatory exudate. There is preliminary evidence that there is an antibody response in B. catarrhalis otitis media. B. catarrhalis has emerged as an important and common pathogen in neonates, infants, and children. PMID- 2111088 TI - A descriptive study of 42 cases of Branhamella catarrhalis pneumonia. AB - PURPOSE: We studied the clinical and laboratory findings of patients with pneumonia due to Moraxella (Branhamella) catarrhalis to better characterize the types of patients who develop this pneumonia, the clinical features of the illness, and the type of and response to drug therapy, as well as the immediate and long-term survival of these patients. PATIENTS AND METHODS: Patients with sputum samples that met cellular criteria as quality samples and that grew B. catarrhalis as the sole pathogen were identified retrospectively from microbiology records at a regional referral hospital for cardiac and pulmonary diseases. Records of these patients were reviewed to identify patients with radiographic findings of pneumonia. Clinical and laboratory characteristics of these patients were then studied in detail. RESULTS: Forty-two patients who met the criteria for B. catarrhalis pneumonia were identified. Most patients were elderly (over 65 years; 55 percent), malnourished (69 percent), and had severe chronic obstructive pulmonary disease or another serious underlying disease (98 percent). The seasonal incidence of this pneumonia was October through April (88 percent), with the annual number of cases having increased since 1982. The clinical presentation was typically mild. Interstitial or mixed interstitial alveolar infiltrates superimposed on pre-existing chronic lung disease was the most common radiographic finding. Approximately 90 percent of sputa were acceptable for Gram stain and contained 10 to more than 50 gram-negative cocci/1,000 x field. All cultures produced a heavy growth of B. catarrhalis, with 67 percent of strains positive for beta-lactamase. No patient had identified bacteremia (zero of 25 tested). Therapy with numerous agents including cefotaxime, amoxicillin/clavulanic acid, and trimethoprim/sulfamethoxazole resulted in a good clinical and bacteriologic response. However, 45 percent of patients died of their underlying diseases on this admission or within three months. CONCLUSION: These findings provide a good profile of B. catarrhalis pneumonia. Despite the mild character of the illness, the pneumonia occurs in patients with end-stage pulmonary or malignant disease and almost 50 percent of patients die of their underlying diseases within three months. PMID- 2111089 TI - Antibody response to P-protein in patients with Branhamella catarrhalis infections. AB - Branhamella catarrhalis is now recognized as an important cause of lower respiratory tract infections, especially in the elderly. In most instances, pathogenicity is presumed by recovery of the organism in a sputum culture, a method that is less than conclusive. In order to better diagnose B. catarrhalis infections, an enzyme-linked immunoassay has been developed using P-protein as antigen to measure antibodies to B. catarrhalis. In 17 elderly patients with B. catarrhalis pneumonia and 12 with tracheobronchitis, acute-phase serum antibody titers to P-protein were found to be significantly increased when compared with those of normal subjects (both p less than 0.02). There were no differences in antibody titers between patients with pneumonia and tracheobronchitis. Antibody titers of convalescent-phase sera increased over those of acute-phase sera in 46 percent of pneumonia patients and 50 percent of tracheobronchitis patients. The results demonstrated that lower respiratory tract infections with B. catarrhalis promote a significant elevation in antibody response to P-protein of B. catarrhalis. PMID- 2111090 TI - A comparison of serum bactericidal activity and phenotypic characteristics of bacteremic, pneumonia-causing strains, and colonizing strains of Branhamella catarrhalis. AB - Four blood isolates, 12 pneumonia isolates, and seven colonizing isolates of Branhamella catarrhalis were compared with respect to their ability to grow in normal human serum and in convalescent serum of a patient with B. catarrhalis bacteremia. Disease-causing isolates showed seven of 16 serum-resistant strains (43 percent) compared with one of seven (13 percent) colonizing strains. Bacteremic strains were not more serum-resistant than pneumonia-causing strains. Trypsin zones of inhibition were higher for disease-causing strains. There was no correlation between source of isolation and colistin sensitivity or ability to hemagglutinate red blood cells. PMID- 2111091 TI - Branhamella catarrhalis: phenotypic characteristics. AB - PURPOSE: This review provides a comprehensive description and discussion of recognized phenotypic characteristics of Branhamella catarrhalis. An emphasis is placed on attributes of this organism that are relevant to its recovery and identification in the clinical microbiology laboratory. In addition, characteristics useful in determining strain identity for use in epidemiologic investigations are addressed. Finally, factors are discussed that may account for the infection-causing potential of B. catarrhalis or at least are of potential consequence to investigations of the pathogenesis of Branhamella disease. CONCLUSIONS: B. catarrhalis is readily isolated from human clinical specimens and can be easily identified using simple, rapid laboratory techniques. Restriction endonuclease analysis of chromosomal deoxyribonucleic acid has proven to be a useful tool in epidemiologic studies. Beta-lactamase isoelectric focusing is of limited value because of the small number of distinct patterns. The lipopolysaccharide and outer membrane proteins of B. catarrhalis have been characterized and found to be relatively non-varying among different strains. Circumstantial evidence exists in support of the hypothesis that the B. catarrhalis beta-lactamase is a virulence determinant. PMID- 2111092 TI - Antibiotic susceptibilities and drug resistance in Moraxella (Branhamella) catarrhalis. AB - PURPOSE: To summarize current knowledge of drug susceptibility and mechanisms of drug resistance in Moraxella (Branhamella) catarrhalis. MATERIALS AND METHODS: The current medical literature was reviewed, with careful attention to recent studies of the BRO beta-lactamases. RESULTS: Although intrinsically resistant to a small group of drugs that included vancomycin and trimethoprim, acquired drug resistance in Branhamella catarrhalis was unknown in the early years of antimicrobial therapy. During 1976 to 1977, however, two previously unrecognized beta-lactamases appeared in this species almost simultaneously around the world. At the same time these enzymes, now known as BRO-1 and BRO-2, also appeared in two closely related commensal species of Moraxella. Within four years the BRO enzymes were found in up to 75 percent of B. catarrhalis in the United States where they provide low-level resistance to penicillin and ampicillin but not to most cephalosporins. The BRO genes appear to be chromosomal but are readily transferred by conjugation within the Moraxella genus. Resistance to aminoglycosides and trimethoprim-sulfamethoxazole has been reported from Spain, and resistance to both erythromycin and tetracycline has recently been described among United States isolates of B. catarrhalis. CONCLUSION: Despite this drug resistance, numerous oral and parenteral agents are available and appear useful for treatment of clinical disease, including amoxicillin/clavulanic acid, erythromycin, the tetracyclines, ciprofloxacin, and trimethoprim/sulfamethoxazole. Recent changes in drug resistance in this species suggest that continued monitoring of drug resistance in B. catarrhalis is needed. PMID- 2111093 TI - Emergence and persistence of beta-lactamase-producing bacteria in the upper respiratory tract in children treated with beta-lactam antibiotics. AB - PURPOSE: To assess the ecologic impact, in terms of selection of beta-lactamase producing respiratory tract bacteria, of a single course of peroral beta-lactam antibiotics. PATIENTS AND METHODS: One-hundred fifty consecutive children with clinical signs of bacterial respiratory tract infection were randomly assigned to a seven-day course of treatment with either penicillin V, amoxicillin, or cefaclor. Bacteriologic specimens were collected before treatment, at its termination, and at follow-up four weeks later. RESULTS: All three drugs investigated caused a similar increase in beta-lactamase-producing bacteria, both in absolute and relative terms, an increase that persisted over a period of at least one month after completion of treatment. CONCLUSION: Penicillin V, amoxicillin, and cefaclor all act as selective agents for beta-lactamase producing bacteria in the upper respiratory tract. Treatment with a peroral beta lactam antibiotic puts patients at risk of becoming persistent carriers of beta lactamase-producing bacteria. PMID- 2111094 TI - Respiratory infections caused by Branhamella catarrhalis. Selected epidemiologic features. AB - PURPOSE: This work reviewed existing literature pertaining to the epidemiologic aspects of respiratory tract infections caused by Branhamella catarrhalis, examined certain epidemiologic features of B. catarrhalis infections occurring at this facility, and identified relevant areas in need of further study. PATIENTS AND METHODS: Literature dealing with the epidemiology of B. catarrhalis infections was reviewed. Records in this Veterans Administration hospital microbiology laboratory were reviewed and all B. catarrhalis isolates and pure cultures of Hemophilus influenzae and Streptococcus pneumoniae were noted for the January 1986 to June 1989 study period. RESULTS: B. catarrhalis is now recognized as a disease-causing pathogen that is particularly noted for its association with acute otitis media in children and lower respiratory tract infections in adults with underlying cardiopulmonary disease. It was recovered from 2.7 percent of all respiratory specimens submitted over a 42-month period at this Veterans hospital. When compared with H. influenzae and S. pneumoniae, B. catarrhalis was found to be the second most commonly isolated respiratory pathogen. It was frequently found in pure culture (53 percent) or in combination with H. influenzae, gram negative bacilli, or S. pneumoniae. The seasonal recovery of B. catarrhalis was apparent for the November to May period compared with the June to October period (p less than 0.001). CONCLUSION: B. catarrhalis has emerged as a major respiratory pathogen in pediatric and adult patient populations. There is a distinct seasonal pattern associated with its recovery and reasons for this are unclear. Prevalence studies aimed at identifying colonization rates among "low" and "high" risk groups are needed. The availability of restriction endonuclease analysis as a typing system for B. catarrhalis should favorably impact upon future epidemiologic studies. Many B. catarrhalis isolates produce beta lactamase, and therapeutic options must reflect this. PMID- 2111095 TI - Suppressive actions of a gonadotropin-releasing hormone antagonist on luteinizing hormone, follicle-stimulating hormone, and prolactin release in estrogen deficient postmenopausal women. AB - We investigated time- and dose-dependent actions of a gonadotropin-releasing hormone antagonist, the "Nal-Glu" peptide [Ac-D2Nal1, 4CIDPhe2, D3Pal3, Arg5, DGlu6(AA), DAla10], in nine healthy estrogen-withdrawn postmenopausal women. Gonadotropin-releasing hormone antagonist was administered subcutaneously at doses of 10, 30, 100, and 300 micrograms/kg. Suppression of immunoactive luteinizing hormone concentrations was achieved with a 30 micrograms/kg dose of antagonist. Suppression of immunoactive follicle-stimulating hormone levels was less (40%) even at the highest antagonist dose (300 micrograms/kg). Bioactive luteinizing hormone concentrations also significantly decreased (greater than 60%) at the two antagonist doses tested (30 and 300 micrograms/kg). However, the lower antagonist dose showed an "escape" of bioactive luteinizing hormone values after 18 hours. No suppressive effects of the antagonist on prolactin secretion occurred at any dose tested. We conclude that this gonadotropin-releasing hormone antagonist can achieve effective, potent, and long-lasting suppression of pituitary secretion of biologically active luteinizing hormone at higher doses, but secretion of biologically active luteinizing hormone may "escape" at lower doses. PMID- 2111096 TI - Interferon gamma and depressed cellular immune response. PMID- 2111097 TI - Corticosteroid treatment of pregnant women with antiphospholipid antibodies and previous fetal loss. PMID- 2111098 TI - A nine year prospective study of Chagas' disease in a defined rural population in northeast Brazil. AB - The association between infection with Trypanosoma cruzi and the development of electrocardiographic alterations and mortality was studied longitudinally for 9 years in a population residing in an endemic area in Castro Alves, Bahia, Brazil. Annual censuses were begun in 1973. At 3 year intervals from 1974 to 1983, the population was examined serologically and subjected to electrocardiography using standardized techniques. Of 1,751 individuals registered during the 10 censuses, 1,541 (88%) were examined serologically at least once. Of 747 individuals in constant residence and originally seronegative, 24 were seropositive upon subsequent evaluation, giving a seroconversion rate of 4.92/1,000 person-years (PY). The overall rate of development of an abnormal ECG was 25.7/1,000 PY for seropositive individuals and 12.5/1,000 PY for seronegative individuals, a relative risk of 2. The 10-14-year-old seropositive group had the highest risk of developing ECG abnormalities (24.1/1,000 PY, relative risk = 3.5). The age adjusted mortality rate of seropositive individuals was slightly higher than for seronegative individuals (8.9 vs. 7.8/1,000 PY). In sero-positive individuals, mortality was strongly associated with the presence of ventricular conduction defects and arrhythmias. Ventricular conduction defects appeared most frequently in younger individuals. Older individuals presented the highest risk of development of frequent and multifocal extrasystoles. PMID- 2111100 TI - [Experience with the use of the CO2 laser in reconstructive and plastic gynecologic surgery in patients with uterine myoma and endometriosis]. AB - CO2 laser has been used during reconstructive plastic surgery for uterine myoma, endometriosis of various locations, and associated gynecologic conditions in 71 patients. Comparison in patients with uterine myoma who underwent conservative myomectomy with and without the use of CO2 laser showed that treatment with CO2 laser diminished blood loss and duration of the operation, and improved postoperative progress. PMID- 2111099 TI - Evaluation of UNICEF/Arab Republic of Egypt/WHO schistosomiasis Control Project in Beheira Governorate. AB - We evaluated the UNICEF/Government of Egypt/WHO Schistosomiasis Control project in 2 districts of Beheira Governorate of the Nile Delta during 3 weeks in February 1988. The project, begun in 1983, was focused on reducing prevalence, intensity, and morbidity due to schistosomiasis by providing diagnosis and treatment with praziquantel to schoolchildren. Schools were visited twice. Following the completion of the school surveys, the program was extended into the community. Chemotherapy was delivered by mobile and static teams. The evaluation indicated that, with respect to accuracy of diagnosis, record-keeping, and coverage of targeted populations, project tasks were performed exceedingly well by highly motivated, well-supervised mobile teams. Static teams in rural health centers were less successful in providing diagnosis and chemotherapy to village populations. We resurveyed 6 randomly selected schools to assess the impact of chemotherapy. Overall, the prevalence of Schistosoma mansoni infection was reduced from 60.3% to 24.8% between the first and second surveys (approximately 1 year apart) and was still lower (41.1%) than initial levels up to 3 years after the last treatment with praziquantel. The percentages of those with greater than or equal to 34 S. mansoni eggs/slide using the Kato-Katz technique showed a marked and prolonged decrease (17.1% to 0.3% to 2.2%). The prevalence of S. haematobium infection dropped from 37.6% to 5.5% and was still 9.9% at the time of the evaluation. The percentages of those with greater than or equal to 50 S. haematobium eggs/10 ml urine dropped less dramatically (17% to 4.4% to 11.9%). Mobile teams conducting vigorous chemotherapy programs targeted at schoolchildren can have long-lasting benefits in terms of prevalence and intensity. PMID- 2111101 TI - [Treatment of cervical and vulvar pathology using lasers of various intensities]. PMID- 2111102 TI - [CO2 embolism during hysteroscopy]. AB - During CO2 hysteroscopy the intracavitary pressure increases up to 80 mmHg. This can result in a CO2 embolism, especially after injury/lesion of the endometrium. A 49-year-old female Caucasian patient underwent curettage, and the following day while a hysteroscopy was being performed in general anesthesia a CO2 embolism occurred, with bradyarrhythmia, drop of arterial blood pressure, superior vena cava syndrome, metallic heartsound and hypercapnia. It was possible to achieve recompensation of the right heart failure with drug therapy. Other causes (lung embolism, hypoventilation, increased CO2 production, cardiac causes) could be excluded. PMID- 2111103 TI - A radiolabel-release microwell assay for proteolytic enzymes present in cell culture media. AB - A modified method for the measurement of proteolytic enzyme activity in cell culture-conditioned media has been developed. Using the release of 3H-labeled peptides from 3H-labeled gelatin the method is performed in microwell plates. The substrate is insolubilized and attached to the wells by glutaraldehyde treatment, thus eliminating the need for a precipitation step at the end of the assay. The assay is sensitive, reproducible, and convenient for small sample volumes. The effect of different protease inhibitors on activity can be assessed rapidly allowing an early characterization of the enzyme. It can also be adapted to microplate spectrophotometric analysis by staining residual substrate with Coomassie blue. PMID- 2111104 TI - Assessing precision and accuracy in blood gas proficiency testing. AB - Blood gas proficiency testing has focused on assessing the accuracy of measurement of each analyte (pH, PCO2) independently of each other. Recently, the American Thoracic Society-California Thoracic Society Blood Gas Proficiency Testing Survey distributed the same lot of ampules of proficiency testing material (a buffered fluorocarbon-containing emulsion) on three occasions within a 1-yr period, allowing us to assess the precision (reproducibility) of measurement of each analyte. Comparing 580 instruments of 13 models, we found that the precision of measurement of each analyte was positively correlated with the precision of measurement of each other analyte, and the correlation of precision between models was much stronger than precision between the individual instruments. We also found correlation of precision of each analyte with two targets for accuracy: (1) the all-instrument mean and (2) the model-specific means. Correlations were higher with the model-specific means. These findings suggest: (1) that features unique to design of each model are important in the precision of measurement of these ampules, and (2) that it would be informative to include measurements of precision with linked and cumulative ratings of analyte accuracy in proficiency testing rating systems. PMID- 2111105 TI - Intrinsic PEEP and arterial PCO2 in stable patients with chronic obstructive pulmonary disease. AB - Dynamic pulmonary hyperinflation and intrinsic PEEP (PEEPi) are known to play an important role in causing acute respiratory failure in COPD patients. In the present study, we have explored (1) the prevalence and magnitude of PEEPi in stable COPD patients, and (2) the correlation of PEEPi with respiratory mechanics and PaCO2. In 96 stable COPD patients with varying degrees of airway obstruction, we measured pulmonary flow resistance (RL), dynamic lung compliance (CLdyn), breathing pattern, arterial blood gases, and dynamic PEEPi. Dynamic PEEPi was determined as a negative deflection in esophageal pressure from the start of inspiratory effort to the onset of inspiratory flow. A significant correlation was found between dynamic PEEPi and FEVi (% predicted; r = -0.56, p less than 0.001), between PEEPi and RL (r = 0.69, p less than 0.001), and between PaCO2 and PEEPi (r = 0.6, p less than 0.001). These results indicate that increased severity of airway obstruction promotes PEEPi and concomitant dynamic hyperinflation. This implies increased inspiratory work in the face of decreased effectiveness of the inspiratory muscles as pressure generators. The present results suggest that dynamic hyperinflation may play a role in causing chronic hypoventilation in COPD patients. PMID- 2111106 TI - Smear-negative, culture-positive pulmonary tuberculosis. Six-month chemotherapy with isoniazid and rifampin. AB - We have shown in Arkansas that 9 months of therapy with isoniazid (INH) and rifampin (RIF) can achieve lasting success in 95% of cases with sputum-smear positive pulmonary tuberculosis. It seemed likely that when the tubercle bacilli were less numerous, i.e., could not be seen on microscopy, less therapy would suffice. Thus, in January 1980, we began giving only 6 months of treatment to patients in whom at least one sputum culture showed M. tuberculosis but at least three sputum smears showed no organisms. The regimen for adults is INH 300 mg and RIF 600 mg daily for 1 month followed by INH 900 mg and RIF 600 mg twice weekly for another 5 months. To date, 286 patients with an average age of 68.2 yr have been treated in this manner. Associated medical conditions were present as "risk factors" in 23.7%. The full course of therapy could not be completed in 75 patients (26.2%), largely because of side effects of the drugs and non-TB deaths in this group of elderly patients. Side effects of the drugs requiring change of drug(s) occurred in 33 patients (11.5%), but major side effects occurred in only eight (2.8%), four (1.4%) with toxic hepatitis and four with hematologic toxicity. The side effects in 25 patients (8.7%) were not life-threatening and were due to drug intolerance. Treatment failed during therapy in only one patient. The full 6-month course of therapy was completed by 211 patients. During follow-up from 3 to 107 months (median, 45 months), five of 211 patients (2.4%) relapsed, all with drug-susceptible organisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111107 TI - Increased lung epithelial permeability in HIV-infected patients with isolated cytotoxic T-lymphocytic alveolitis. AB - HIV-related lymphocytic alveolitis is common in HIV-seropositive patients without lung infection or tumor. In some of them a fraction of alveolar lymphocytes are HIV-specific cytotoxic T-lymphocytes (CTL) bearing the CD8 and D44 cell surface markers and capable of killing HIV-infected alveolar macrophages. In order to evaluate the in vivo effect of these CTL on lung function, we measured the pulmonary clearance of aerosolized 99mTc-diethylene triamine penta-acetate (DTPA CI) on 24 occasions in 22 patients with lymphocytic alveolitis. DTPA-CI has been selected as a highly sensitive test to detect injury of the lung epithelium. In 13 of the patients, we found a high DTPA-CI of 4.56 +/- 2.54%.min-1 (mean +/- SD), suggesting an increase of the epithelial permeability. The lymphocytic alveolitis was then characterized by a high cellularity, a high proportion of lymphocytes (59 +/- 18%), mainly composed of CD8+D44+ T-lymphocytes (149 +/- 109 cells/mm3), which spontaneously exhibited a cytolytic activity against the autologous alveolar macrophages in a standard 51Cr release assay. In the remaining 11 patients, DTPA-CI was normal (less than 1.78%.min-1), lymphocytic alveolitis being characterized by a low number or an absence of CD8+D44+ alveolar lymphocytes (9 +/- 13 cells/mm3) with no significant cytolytic activity. In the whole group, a significant correlation (r = 0.74, p = 0.0004) was found between the DTPA-CI and the number of CD8+D44+ lymphocytes and their cytotoxic activity against alveolar macrophages. Altogether, these results suggest that an injury of the lung epithelium could result from a HIV-specific CTL-induced immunologic conflict. PMID- 2111108 TI - Hepatitis C virus infection in patients with nonalcoholic chronic liver disease. AB - STUDY OBJECTIVE: To determine the prevalence and meaning of antibodies to the hepatitis C virus (HCV) in patients with nonalcoholic chronic liver diseases. DESIGN: Cross-sectional study. SETTING: The liver unit of a referral-based university hospital. PATIENTS: Three hundred and forty-six consecutive patients, including 137 with cryptogenic chronic liver disease, 156 with chronic hepatitis B, 47 with primary biliary cirrhosis, and 8 with persistently abnormal aminotransferase serum levels and normal liver histology. Among patients with cryptogenic liver disease, 41 received blood transfusions before discovery of liver disease and 18 had circulating nonorgan-specific autoantibodies. For comparison, 1495 apparently healthy volunteer blood donors were included in the study. LABORATORY INVESTIGATIONS: The presence of anti-HCV antibodies (anti-HCV) was determined by a recently developed enzyme-linked immunoassay. MEASUREMENTS AND MAIN RESULTS: In patients with cryptogenic liver disease, the prevalence of anti-HCV was 82% (95% CI, 76% to 89%), being higher (P = 0.02) in patients with histories of blood transfusion than in those with unknown sources of exposure. Antibodies to HCV were not detected in patients with antinuclear antibodies at high titer. Among patients with chronic hepatitis B, anti-HCV were found in 11% (CI, 5% to 18%) of those with hepatitis B virus (HBV)-associated DNA in serum and in 29% (CI, 17% to 43%) of those with undetectable HBV replication (P less than 0.05). The prevalence of anti-HCV in blood donors was 1.2% (CI, 1.1% to 1.3%). CONCLUSIONS: Our results indicate that HCV infection probably plays an important etiologic role in cryptogenic liver disease and, in some patients, in chronic hepatitis B. Determining whether anti-HCV are present appears to be useful for differentiating viral from autoimmune chronic liver diseases. PMID- 2111109 TI - Efficient management of diarrhea in the acquired immunodeficiency syndrome (AIDS). A medical decision analysis. AB - STUDY OBJECTIVE: To compare the efficacy and cost effectiveness of alternative strategies for the evaluation and medical management of diarrhea in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Medical decision analysis using a decision tree. METHODS: Three management strategies were compared: full evaluation, which included stool culture, ova and parasite examination, stain for protozoa, blood cultures, esophagogastroduodenoscopy with biopsy, and colonoscopy with biopsy; limited evaluation, which included stool culture, ova and parasite examination, stool stain for protozoa, and blood cultures; and minimal evaluation, which included only a stool culture. Treatment was based on the outcome of the diagnostic workup. Patients without a specific diagnosis were treated symptomatically with diphenoxylate hydrochloride. Nonrespondents to initial symptomatic treatment and patients with recurrent diarrhea after specific therapy were given the full evaluation. Average probabilities of diagnostic and therapeutic success were calculated from previous reports. Costs were compiled based on diagnostic and therapeutic expenditures. MEASUREMENTS AND MAIN RESULTS: Under baseline assumptions, the remission rates for diarrhea were 75.2%, 74.8%, and 74.8% in patients undergoing the full, limited, and minimal evaluations, respectively. The respective costs of the three strategies were $5419, $1997, and $1700 per patient in remission. A sensitivity analysis showed that the differences in efficacy and cost among the full, limited, and minimal strategies remained unchanged over a broad range of possible rates of diagnostic or therapeutic success. CONCLUSIONS: The minimal evaluation in all patients, with the full evaluation reserved only for nonrespondents to symptomatic treatment, is efficacious and is the most cost-effective strategy for managing AIDS-related diarrhea. PMID- 2111110 TI - The prevalence of hepatitis C virus antibodies among hemodialysis patients. PMID- 2111111 TI - Cloning, sequence analysis, and expression of genes encoding xylan-degrading enzymes from the thermophile "Caldocellum saccharolyticum". AB - A lambda recombinant bacteriophage coding for xylanase and beta-xylosidase activity has been isolated from a genomic library of the extremely thermophilic anaerobe "Caldocellum saccharolyticum." Partial Sau3AI fragments of the lambda recombinant DNA were ligated into pBR322. A recombinant plasmid with an insertion of ca. 7 kilobases of thermophilic DNA expressing both enzymatic activities was isolated. The location of the genes has been established by analyzing deletion derivatives, and the DNA sequence of 6.067 kilobases of the insert has been determined. Five open reading frames (ORFs) were found, one of which (ORF1; Mr 40,455) appears to code for a xylanase (XynA) which also acts on o-nitrophenyl beta-D-xylopyranoside. Another, ORF5 (Mr 56,365), codes for a beta-xylosidase (XynB). The xynA gene product shows significant homology with the xylanases from the alkalophilic Bacillus sp. strain C125 and Clostridium thermocellum. PMID- 2111112 TI - Sequential anaerobic degradation of 2,4-dichlorophenol in freshwater sediments. AB - 2,4-Dichlorophenol (2,4-DCP) was anaerobically degraded in freshwater lake sediments. From observed intermediates in incubated sediment samples and from enrichment cultures, the following sequence of transformations was postulated. 2,4-DCP is dechlorinated to 4-chlorophenol (4-CP), 4-CP is dechlorinated to phenol, phenol is carboxylated to benzoate, and benzoate is degraded via acetate to methane and CO2; at least five different organisms are involved sequentially. The rate-limiting step was the transformation of 4-CP to phenol. Sediment-free enrichment cultures were obtained which catalyzed only the dechlorination of 2,4 DCP, the carboxylation of phenol, and the degradation of benzoate, respectively. Whereas the dechlorination of 2,4-DCP was not inhibited by H2, the dechlorination of 4-CP, and the transformation of phenol and benzoate were. Low concentrations of 4-CP inhibited phenol and benzoate degradation. Transformation rates and maximum concentrations allowing degradation were determined in both freshly collected sediments and in adapted samples: at 31 degrees C, which was the optimal temperature for the dechlorination, the average adaptation time for 2,4 DCP, 4-CP, phenol, and benzoate transformations were 7, 37, 11 and 2 days, respectively. The maximal observed transformation rates for these compounds in acclimated sediments were 300, 78, 2, 130, and 2,080 micromol/liter(-1)/day(-1), respectively. The highest concentrations which still allowed the transformation of the compound in acclimated sediments were 3.1 m/M 2,4-DCP, 3.1 mM 4-CP, 13 mM phenol, and greater than 52 mM benzoate. The corresponding values were lower for sediments which had not been adapted for the transformation steps. PMID- 2111113 TI - Same-day identification scheme for colonies of Listeria monocytogenes. AB - A diagnostic scheme is described for the same-day identification of food-borne cells of Listeria monocytogenes that emerge in 40 h at 30 degrees C as large colonies, representatives of which are used to advantage as heavy inocula on agar plates for the rapid determination of hemolytic activity and acidification of rhamnose and xylose. Additional tests consisting of phase-contrast microscopy for cell morphology and motility, the catalase production test, and the KOH viscosity test in place of Gram staining complete the rapid identification scheme. PMID- 2111114 TI - Chemical germination of native and cation-exchanged bacterial spores with trifluoperazine. AB - The calmodulin antagonist trifluoperazine and its analog chlorpromazine, both amphipaths, induced chemical germination of spores of various species, as do many surfactants. Cation load can greatly influence this response. Calmodulin antagonism does not seem to be involved. A new fluorometric assay for dipicolinic acid based on the fluorescence of the dipicolinic acid chelate of Tb3+ was found to be simple and sensitive. PMID- 2111115 TI - Microbiological quality and safety of zoo food. AB - Two types of commercial products for feeding zoo animals (a frozen meat product, referred to as zoo food, and a dry product, referred to as dry food) were microbiologically examined for spoilage organisms (aerobic, psychrotrophic, coliform, Escherichia coli, mold, and yeasts) and pathogens (Salmonella spp., Listeria monocytogenes, and Campylobacter jejuni). Levels of microorganisms in frozen ground zoo food were compared with those in frozen ground beef and frozen ground turkey meat. The level of microbial contaminants in frozen ground zoo meat was found to be similar to that in frozen ground beef and higher than that in frozen ground turkey meat. Sixty percent of the frozen zoo meat samples were Salmonella positive, and all of the samples were L. monocytogenes positive. Dry zoo food was documented to have microbial levels lower than those in frozen zoo meat; the pathogen levels were less than 1/25 g of food. Defrosting zoo meat at 10, 25, and 37 degrees C for 24 h showed that 10 degrees C is the best temperature for defrosting frozen ground zoo meat loaves (length, 9 in. [22.8 cm]; radius, 2 in. [5.1 cm]) without affecting the microbiological quality or safety of the product. PMID- 2111116 TI - Construction of lactose-utilizing Xanthomonas campestris and production of xanthan gum from whey. AB - Xanthomonas campestris pv. campestris possesses a low level of beta-galactosidase and therefore is not able to grow and produce significant amounts of xanthan gum in a medium containing lactose as the sole carbon source. In this study, a beta galactosidase expression plasmid was constructed by ligating an X. campestris phage phi LO promoter with pKM005, a ColE1 replicon containing Escherichia coli lacZY genes and the lpp ribosome-binding site. It was then inserted into an IncP1 broad-host-range plasmid, pLT, and subsequently transferred by conjugation to X. campestris 17, where it was stably maintained. The lacZ gene under the control of the phage promoter was expressed at a high level, enabling the cells to grow in a medium containing lactose. Production of xanthan gum in lactose or diluted whey by the engineered strain was evaluated, and it was found to produce as much xanthan gum in these substrates as the cells did in a medium containing glucose. PMID- 2111117 TI - Formation of deglycosylated alpha-L-fucosidase by endo-beta-N acetylglucosaminidase in Fusarium oxysporum. AB - Two forms of alpha-L-fucosidase, deglycosylated and glycosylated, were found in the fucose-inducing culture broth of Fusarium oxysporum. Endo-beta-N acetylglucosaminidase was also found in the same culture broth. The deglycosylated alpha-L-fucosidase was purified from the culture broth to homogeneity on polyacrylamide disc gel electrophoresis and analytical ultracentrifugation. Purified deglycosylated alpha-L-fucosidase was compared in chemical composition and immunological homology with glycosylated alpha-L fucosidase which had been reported previously (K. Yamamoto, Y. Tsuji, H. Kumagai, and T. Tochikura, Agric. Biol. Chem. 50: 1689, 1986). Both enzymes had nearly the same amino acid compositions and were immunologically identical. Glycosylated alpha-L-fucosidase had mannose, galactose, and N-acetylglucosamine residues. In contrast, the deglycosylated enzyme had only N-acetylglucosamine residues. These results suggest that the deglycosylated alpha-L-fucosidase is formed by the release of sugar chains from the glycosylated form by Fusarium endo-beta-N acetylglucosaminidase. Furthermore, various enzymatic properties were compared: the two alpha-L-fucosidases were found to exhibit similar catalytic activities and thermal stability profiles. The deglycosylated enzyme, however, was slightly unstable in the acidic pH range compared with the glycosylated enzyme. PMID- 2111119 TI - L-lysine production at 50 degrees C by mutants of a newly isolated and characterized methylotrophic Bacillus sp. AB - The amino acid L-lysine was produced from homoserine auxotrophic and S-(2 aminoethyl)-L-cysteine-resistant mutants of a newly isolated gram-positive methylotrophic bacterium, capable of growth on methanol at 60 degrees C. The temperature optimum for growth was between 50 and 53 degrees C. These aerobic, gram-positive, endospore-forming, rod-shaped bacteria required biotin and vitamin B12 for growth. Extracts of the bacteria grown on methanol lacked hydroxypyruvate reductase and contained hexulose 6-phosphate synthase activity. Therefore, these bacteria were considered to be type I methylotrophic bacteria of the genus Bacillus. Fed-batch fermentations resulted in cell densities of 50 g of cell dry weight per liter. Biomass yields on carbon, nitrogen, phosphate, and sulfate were determined. Generation of homoserine auxotrophic and amino acid analog-resistant mutants resulted in L-lysine concentrations of nearly 20 g/liter in fed-batch fermentations. PMID- 2111118 TI - Molecular characterization of promoters of the Lactococcus lactis subsp. cremoris temperate bacteriophage BK5-T and identification of a phage gene implicated in the regulation of promoter activity. AB - DNA fragments from the temperate lactococcal bacteriophage BK5-T were cloned into the promoter-detecting plasmid pMU1328. Five DNA fragments conferring promoter activity were selected by transformation of Streptococcus sanguis and were functional in Escherichia coli, S. sanguis, and Lactococcus lactis subspp. lactis and cremoris. The nucleotide sequences of these fragments were determined, and primer extension analysis was used to locate the site of initiation of transcription from each promoter in both E. coli and S. sanguis. Transcription was initiated from the same nucleotide in these two organisms, and the promoters contained -10 and -35 regions similar to the consensus sequence for E. coli promoters. The activities of three of the five promoters were decreased two- to threefold when a compatible plasmid containing a 3.8-kilobase-pair EcoRI fragment (EcoRI-f) of BK5-T was coresident with the promoter-containing plasmid in either L. lactis subsp. cremoris or E. coli. Data from Tn5 mutagenesis, subcloning experiments, and DNA sequence analysis indicate that this decrease in promoter activity requires a region of EcoRI-f that contains a 621-base-pair open reading frame. This region has been designated bpi (for BK5-T promoter inhibitor). PMID- 2111120 TI - Pathogenicity of Listeria monocytogenes grown on crabmeat. AB - The pathogenicity of Listeria monocytogenes as influenced by growth on crabmeat at 5 and 10 degrees C was studied. Crabmeat was inoculated with L. monocytogenes V7 (ca. 10(4) CFU/g) and incubated for up to 14 days at 5 and 10 degrees C. At selected incubation times, L. monocytogenes was removed from crabmeat by washing with 0.1 M potassium phosphate buffer (pH 7.0), and populations were determined by surface plating on LiCl-phenylethanol-moxalactam agar. Buffered suspensions were then centrifuged, and the resulting pellets were suspended in phosphate buffer containing 10% glycerol and stored at -18 degrees C. Thawed, diluted suspensions of cells were tested for pathogenicity by intraperitoneal injection into immunocompromised and nonimmunocompromised mice. L. monocytogenes cells recovered from crabmeat and then recultured in tryptose phosphate broth (TPB), as well as cells which had not been passed through crabmeat but had been cultured in TPB, were likewise harvested, suspended in buffered 10% glycerol, frozen, thawed, diluted, and tested for pathogenicity by intraperitoneal injection. Growth on crabmeat at 5 and 10 degrees C did not have a significant effect on pathogenicity. The population of L. monocytogenes necessary to kill about 50% of the immunocompromised mice in each test set within 7 days was about 10(4) CFU, and this result was not significantly affected by storage temperature of the crabmeat or type of substrate, i.e., crabmeat or TPB, on which it had grown. PMID- 2111121 TI - Purification and characterization of purine nucleoside phosphorylase from Proteus vulgaris. AB - Purine nucleoside phosphorylase was isolated and purified from cell extracts of Proteus vulgaris recovered from spoiling cod fish (Gadus morhua). The molecular weight and isoelectric point of the enzyme were 120,000 +/- 2,000 and pH 6.8. The Michaelis constant for inosine as substrate was 3.9 x 10(-5). Guanosine also served as a substrate (Km = 2.9 x 10(-5). However, the enzyme was incapable of phosphorylizing adenosine. Adenosine proved to be useful as a competitive inhibitor and was used as a ligand for affinity chromatography of purine nucleoside phosphorylase following initial purification steps of gel filtration and ion-exchange chromatography. PMID- 2111122 TI - Interconversion of aflatoxin B1 and aflatoxicol by several fungi. AB - Four fungal strains, namely, Aspergillus niger, Eurotium herbariorum, a Rhizopus sp., and non-aflatoxin (AF)-producing Aspergillus flavus, which could convert AF B1 to aflatoxicol (AFL), could also reconvert AFL to AF-B1. The interconversion of AF-B1 to AFL and of AFL to AF-B1 was ascertained to occur during proliferation of the fungi. These reactions were distinctly observed in cell-free systems obtained from disrupted mycelia of A. flavus and the Rhizopus sp., but they were not observed in culture filtrates from intact (nondisrupted) mycelia of the same strains. The interconversion activities of AF-B1 and AFL were not observed when the cell-free systems were preheated at 100 degrees C. These findings strongly suggest that the interconversion of AF-B1 and AFL is mediated by intracellular enzymes of A. flavus and the Rhizopus sp. In addition, the isomerization of AFL-A to AFL-B observed in culture medium was also found to occur by the lowering of the culture pH. PMID- 2111124 TI - Genes associated with rheumatoid arthritis and mild inflammatory arthritis. II. Association of HLA with complement C3 and immunoglobulin Gm allotypes. AB - Associations were sought between major histocompatibility complex (MHC) genes on chromosome 6 and the complement component C3 and immunoglobulin genes located on other chromosomes which might contribute to susceptibility to mild inflammatory arthritis (IA) or definite rheumatoid arthritis (RA). Frequencies of the complement C3F allele were raised in patients with IA but were normal in patients with RA and controls. When associations between C3F and MHC genes were sought frequencies of some MHC genes were greater in patients with C3F than in those without--for example, HLA-B8 and DR3 in patients with RA and DR2 in patients with IA. Conversely, DR4 frequency was lower in patients with IA with C3F than in those without. Thus the C3F allele may act independently or exert an epistatic effect on MHC genes to increase susceptibility or protect against disease. The frequency of the immunoglobulin heavy chain allotype Glm(2) on chromosome 14 was increased in patients with RA but only in those with the phenotype Gm1,2,3,17;21,5; no significant associations were found between MHC genes and Gm phenotypes. Further, no associations of MHC, C3F, and immunoglobulin genes were shared by patients with RA and those with IA, indicating a different genetic basis for the two clinical entities. PMID- 2111123 TI - Genes associated with rheumatoid arthritis and mild inflammatory arthritis. I. Major histocompatibility complex class I, II, and III allotypes. AB - Patients with mild inflammatory arthritis (IA) were compared with patients with definite rheumatoid arthritis (RA) for abnormal frequencies of major histocompatibility complex (MHC) antigens and haplotypes to determine whether a genetic predisposition either to RA or to mild self-limiting arthritis/arthralgia was present in the patients with IA. In general the MHC antigens with abnormal frequencies found in patients with IA differed from those in patients with RA and were mainly at the A and B loci. In patients with IA the frequencies of HLA-A24, A25, B27, and B35 antigens were significantly higher than those of controls and HLA-DR5 and C4A4 were slightly raised. In contrast, in patients with RA abnormal frequencies of the MHC antigens DR4 and DR2 and the extended haplotypes associated with them [B62 BfS C4A3 C4B3 DR4 GLO2] and [B7 BfS C4A3 C4B1 DR2] confirmed the observations reported on other white populations. Thus MHC antigen associations with IA and RA differ sufficiently to suggest a different genetic basis for the two conditions. PMID- 2111125 TI - Protein malnutrition predisposes to inflammatory-induced gut-origin septic states. AB - The development of an uncontrolled inflammatory response has been implicated in the pathogenesis of adult respiratory distress syndrome and multiple-organ failure. Because zymosan activates complement and induces a systemic inflammatory response, the effect of zymosan on intestinal structure and barrier function was measured in normally nourished (NN) and protein malnourished (PM) mice. Normally nourished and protein malnourished (up to 21 days) mice challenged intraperitoneally with zymosan (0.1 mg/g body weight) were killed 24 hours after zymosan challenge and their organs cultured for translocating bacteria. Zymosan induced bacterial translocation was limited to the mesenteric lymph nodes of the NN mice, whereas translocating bacteria spread from the gut to the liver, spleen, and blood stream (p less than 0.05) in the PM mice. Zymosan-induced bacterial translocation appeared to be related primarily to the combination of mucosal injury and a disruption of the gut flora ecology in the PM mice and to mucosal injury in the NN mice. The extent of mucosal injury was greater the longer the mice were protein malnourished before zymosan challenge. The effect of zymosan on survival was measured in separate groups of mice. At a dose of 0.1 mg/g body weight, no deaths occurred in NN mice or in 7-day PM mice. However 20% of the 14 day PM mice and 80% of the 21-day PM mice receiving zymosan died. Thus PM predisposes to mucosal damage and the development of potentially lethal gut origin septic state during periods of systemic inflammation. PMID- 2111127 TI - Comparison of prostacyclin production of human gastroepiploic artery and saphenous vein. AB - The prostacyclin production of the gastroepiploic artery (GEA) and saphenous vein (SV) were studied in 5 patients undergoing coronary artery revascularization. The GEA produced 90.0 +/- 11.9, 132.4 +/- 13.7, and 191.1 +/- 21.8 pg/mg tissue (mean +/- standard error of the mean) of 6-keto-prostaglandin F1 alpha (prostacyclin metabolite) after 2.5, 5.0, and 10.0 minutes, respectively, of incubation in Krebs-Henseleit buffer at 37 degrees C. The SV produced 39.8 +/- 7.0, 66.7 +/- 9.1, and 123.6 +/- 15.1 pg/mg tissue of 6-keto prostaglandin F1 alpha after 2.5, 5.0, and 10.0 minutes, respectively, of incubation. The GEA produced significantly more 6-keto-prostaglandin F1 alpha than SV at all three sampling times up to ten minutes of incubation (p less than 0.01). Prostacyclin is a potent vasodilator and an inhibitor of platelet aggregation. Prostacyclin production by the internal mammary artery was reported to be much higher than that of SV, and the patency rate of internal mammary artery grafts is reported to be better than that of SV grafts in coronary artery revascularization. Therefore, our results suggest that the patency rate of GEA grafts may be better than that of SV grafts in coronary artery revascularization. The GEA is a promising and excellent graft from the biochemical point of view. PMID- 2111128 TI - Experimental metastasis inhibition by pretreatment of the host. AB - In an experimental murine metastasis model host pretreatment protocol (HPP) was tested to abrogate lung colonization of tumor cells. The stimulation of the host defense by lentinan or TP4, and the PGI2 administration was effective in the case of the immunosensitive low metastatic tumor. The modulation of the host cells and/or the extracellular matrix by the glycosaminoglycan biosynthesis blocking agent KL-103--but not by the degradation inhibitor suramin--inhibited the lung colonization of the highly metastatic immunoresistant tumor variant. In combination with the cytotoxic antiproliferative agents these non-toxic drugs could be useful in new protocols to prevent tumor dissemination. PMID- 2111126 TI - Beneficial effect of enhanced macrophage function in the trauma patient. AB - Host immunosuppression after trauma contributes to septic morbidity. The macrophage is a key element in the host immune response. This study evaluated glucan, a macrophage stimulant, in a prospective, randomized, double-blind study of 38 trauma patients undergoing surgery. Glucan (21 patients), 50 mg/m2, or placebo (17 patients) was given intravenously daily for 7 days. Delayed hypersensitivity skin testing was performed on days 1 and 7 after trauma. Serum interleukin-1 (IL-1) and tumor necrosis factor (TNF) were assayed after trauma. While the total mortality rate was significantly less in the glucan group (0% versus 29%) (p less than 0.05), the mortality rate from sepsis was not statistically different (0% versus 17.6%). Glucan therapy significantly decreased septic morbidity (9.5% versus 49%; p less than 0.05). Serum IL-1 had a greater increase in glucan patients on day 3 after trauma (143.4 +/- 19.3% versus 78.6 +/ 11.7%; p less than 0.05), but there was no difference thereafter. Serum TNF did not vary between groups. Early increase in IL-1 correlated with subsequent skin test conversion to positive. Neither serum IL-1 nor TNF was a reliable indicator of future sepsis. Further clinical trials are indicated to evaluate biologic response modifiers that activate macrophages in the trauma patient. PMID- 2111129 TI - The use of 13C-n.m.r. spectroscopy to monitor alginate biosynthesis in mucoid Pseudomonas aeruginosa. AB - The biosynthesis of alginate by a mucoid strain of Pseudomonas aeruginosa, isolated from a cystic-fibrosis patient, was monitored by using 13C-n.m.r. spectroscopy of bacterial cultures incubated with 1-13C- or 2-13C-enriched fructose. When 1-13C- or 2-13C-enriched fructose was used as the precursor of alginate, enrichment with 13C in the constituent uronic acid monomers of the polysaccharide could only be detected in C-1 or C-2 respectively, indicating that alginate is synthesized in Ps. aeruginosa directly from fructose, with the hexose molecule being retained intact; this rules out the involvement of C3 intermediates, which occurs when glucose is the alginate precursor. The absence of detectable poly-L-gluluronate block sequences from the alginate of Ps. aeruginosa was confirmed, and it was shown that there is no modification of the arrangement of the constituent uronic acids between polymerization to form alginate and the appearance of the mature alginate in the extracellular medium. The 13C-n.m.r. data also provided independent evidence for acetylation on D mannuronate residues and for the ratio of D-mannuronate to L-guluronate residues in newly synthesized alginate, which had previously been determined only for material secreted from bacteria into the extracellular medium. PMID- 2111130 TI - Reversible and irreversible cross-linking of immunoglobulin heavy chains through their carbohydrate residues. AB - After periodate oxidation and incubation with a dihydrazide, cross-linking of the two heavy chains of immunoglobulins G from several species proceeds specifically through their oligosaccharides. We have used malonic acid dihydrazide, adipic acid dihydrazide and dithiodipropionic acid dihydrazide. The last compound is introduced in this work as a cleavable-carbohydrate-specific cross-linker. It was found that in rabbit and human immunoglobulins the degree of cross-linking was strongly dependent on the oxidation conditions but only very weakly dependent on the concentration and size of the dihydrazides. Papain cleavage of the cross linked rabbit IgG indicated that the cross-linking occurred predominantly, if not exclusively, in the Fc region, probably through the two glycans linked to Asn-297 in the CH2 domain of each of the two heavy chains. The immunoglobulins from sheep, pig, goat and guinea pig show a comparable cross-linking pattern, indicating that the sugar chains from these immunoglobulins have a spatial structure closely related to that of rabbit and human IgG. When dithiodipropionic acid dihydrazide was used as the cross-linker, the cross-link could be cleaved by mercaptoethanol. PMID- 2111131 TI - Chemical modification by pyridoxal 5'-phosphate and cyclohexane-1,2-dione indicates that Lys-7 and Arg-10 are involved in the p2 phosphate-binding subsite of bovine pancreatic ribonuclease A. AB - Steric and chemical evidence had previously shown that residues Lys-7 and/or Arg 10 of bovine pancreatic RNAase A could belong to the p2 phosphate-binding subsite, adjacent to the 3' side of the main site p1. In the present work chemical modification of the enzyme with pyridoxal 5'-phosphate and cyclohexane 1,2-dione was carried out in order to identify these residues positively as part of the p2 site. The reaction with pyridoxal 5'-phosphate yields three monosubstituted derivatives, at Lys-1, Lys-7 and Lys-41. A strong decrease in the yield of derivatives at Lys-7 and Lys-41 was observed when either p1 or p2 was specifically blocked by 5'-AMP or 3'-AMP respectively. These experiments indicate that both sites are needed for the reaction of pyridoxal 5'-phosphate with RNAase A to take place. The positive charge in one of the sites interacts with the phosphate group of pyridoxal 5'-phosphate, giving the proper orientation to the carbonyl group, which then reacts with the lysine residue present in the other site. The absence of reaction between pyridoxal 5'-phosphate and an RNAase derivative that has the p2 site blocked supports this hypothesis. Labelling of Lys-7 with pyridoxal 5'-phosphate has a more pronounced effect on the kinetics with RNA than with the smaller substrate 2',3'-cyclic CMP. In addition, when the phosphate moiety of the 5'-phosphopyridoxyl group was removed with alkaline phosphatase the kinetic constants with 2',3'-cyclic CMP returned to values very similar to those of the native enzyme, whereas a higher Km and lower Vmax. were still observed for RNA. This indicates that this new derivative has recovered a free p1 site and, hence, the capability to act on 2',3'-cyclic CMP, but the presence of the pyridoxyl group bound to Lys-7 is still blocking a secondary phosphate-binding site, namely p2. Finally, reaction of cyclohexane-1,2-dione at Arg-10 is suppressed in the presence of 3'-AMP but only a 19% decrease is observed with 5'-AMP, suggesting that Arg-10 is also close to the p2 phosphate binding subsite. PMID- 2111132 TI - Polyamine regulation of heat-shock-induced spermidine N1-acetyltransferase activity. AB - The enzyme spermidine/spermine N1-acetyltransferase (N1-SAT) is rapidly induced by heat shock in CHO and A549 cells, with activity declining by 24 h. Depletion of intracellular polyamines by alpha-difluoromethylornithine, an inhibitor of ornithine decarboxylase, blocks this induction. Re-addition of putrescine to these cultures restores the response to heat shock, with a concomitant increase in intracellular N1-acetylspermidine. Diaminopropane is more than twice as effective as the naturally occurring diamine putrescine, suggesting that the propylamine moiety of spermidine is involved in the regulation of N1-SAT induction. Inhibitor studies indicate transcriptional activation and that the enzyme has an apparent half-life of 30-60 min. A second heat shock rapidly inhibits induced N1-SAT activity, which decays with a half-life of 2-3 min. Despite its induction by heat, N1-SAT is not a stable enzyme, suggesting that the activity observed is not due to a modification of an existing peptide, but is due to a transcriptional event, which may justify the inclusion of this enzyme in the family of heat-shock proteins. PMID- 2111133 TI - Substrate and inhibitor studies with human gastric aspartic proteinases. AB - The separation of pepsin isoenzymes 1, 2, 3 and 5 (gastricsin) in human gastric juice was effected by chromatography on Mono Q ion-exchanger, and slow-moving proteinase was purified to homogeneity by using a modified procedure incorporating a novel affinity-chromatography step. The pH-activity profiles of these enzymes with mucus glycoprotein and basement-membrane substrates were determined; the profiles for pepsin 2 were noticeably different, and, in general, the pH optima for the hydrolysis of basement membrane were more acidic. Pepsin 1 expressed larger specificity constants (kcat./Km) than pepsin 3 with a series of synthetic peptide substrates, reflecting greater binding (smaller Km) by pepsin 1. Inhibitor studies at pH 1.7 and 4.5 with a series of P2-substituted lactoyl pepstatins implied that valine at position P2 was optimal for inhibiting pepsins 1, 2 and 3 but detrimental for pepsin 5, whereas lysine at position P2 was tolerated well by pepsin 5 but not by pepsins 1, 2 and 3. The potency of lactoyl pepstatin with lysine at position P2 did not increase as a function of pH. P2 substituted lactoyl-pepstatins failed to show any inhibitory selectivity among pepsins 1, 2 and 3. PMID- 2111134 TI - Sequence similarity between Pseudomonas dihydrodiol dehydrogenase, part of the gene cluster that metabolizes polychlorinated biphenyls, and dehydrogenases involved in metabolism of ribitol and glucitol and synthesis of antibiotics and 17 beta-oestradiol, testosterone and corticosterone. PMID- 2111135 TI - Mutation rates to 4-quinolone resistance. AB - The sensitivity of Staph. aureus, Staph. warneri, Pseudomonas aeruginosa, Strep. pneumoneae and Strep. faecalis to eleven 4-quinolone antibacterials was compared by determining their minimum inhibitory concentrations on nutrient agar. In all cases where the minimum inhibitory concentration was less than 10 micrograms/ml then the frequency at which 4-quinolone-resistant mutants arose was estimated using each drug at 5, 10 and 20 times its minimum inhibitory concentration. It was found with all five bacterial species tested that ciprofloxacin and ofloxacin were the most potent antibacterial and that no mutants could be detected in 10(12) bacteria for either drug with Staph. warneri, Strep. pneumoneae and Strep. faecalis. On the other hand, mutants of Pseudomonas aeruginosa resistant to both 5 and 10 times (but not 20 times) the minimum inhibitory concentrations of ofloxacin and ciprofloxacin were detected at similar frequencies in the 10(12) bacteria tested. With Staph. aureus, mutants resisting 5 times (but not 10 or 20 times) the minimum inhibitory concentrations of ofloxacin and ciprofloxacin were detected in the 10(12) bacteria tested at similar frequencies. However, all mutants resistant to ciprofloxacin retained the ability to produce coagulase while the majority of ofloxacin-resistant mutants had lost their ability to produce coagulase. Hence clear evidence for pathogenicity loss was observed with ofloxacin but not with ciprofloxacin. PMID- 2111137 TI - [New aspects of blood component therapy]. AB - The medical demand for factor VIII is increasing through continuously improved therapy of patients suffering from haemophilia A. The most important raw material for the production of factor VIII is fresh frozen plasma (FFP). Its clinical usage increased in the last few years dramatically. An alternative to FFP is the high grade blood component cryo-poor plasma (CPP). CPP is characterized by a deficiency of factor VIII and fibrinogen which is not of clinical relevance. It can be used instead of FFP in 95% of cases. Thus, FFP is more available for the production of factor VIII and the supply of factor VIII for haemophiliacs will improve. PMID- 2111136 TI - Monoclonal antibodies directed against human Rh antigens in tests with the red cells of nonhuman primates. AB - Monoclonal antibodies against Rh related antigens on human red cells often crossreact with the red cells of the highest subhuman primate species. Depending on specificity of antibody, the species tested, and technique used, these reactions can be either species-specific or type specific. In tests with chimpanzee red cells, some of the latter type reactions have specificities related to the R antigen of the R-C-E-F blood group system of chimpanzee; specificities of some others seem to be unrelated to any known chimpanzee blood groups. Monoclonal anti-D reagents that give uniformly positive reactions with human D-positive (common and rare types) red cells, display wide individual differences in tests with chimpanzee blood. This indicates that there are minute structural variations of antibody molecules from one monoclonal anti-D antibodies apparently have no bearing on recognition of the D combining site on the human red cells, but come into play when in contact with chimpanzee rbcs. Some of the monoclonal antibodies directed against Rh and LW molecules are distinguished by unusually strong reactions with the red cells of the Old World monkeys (macaques and baboons), which is in contrast with negative or weak reactions of the same antibodies with the red cells of anthropoid apes and human bloods. One may recall, that polyclonal anti-Rh sera do not react with the blood of rhesus monkeys, the phenomenon that was the source of controversy surrounding the discovery of the rhesus factor of the human blood. PMID- 2111138 TI - Interferon-gamma sensitizes rat pancreatic islet cells to lysis by cytokines and cytotoxic cells. AB - Immunoregulatory polypeptides (cytokines) produced by mononuclear cells of the immune system can inhibit insulin secretion and may be cytotoxic to pancreatic islet beta cells. We used a modified 51Cr release cytotoxicity assay to define the interactive cytotoxic effects of interleukin-1 (IL-1), tumor necrosis factor (TNF), and interferon gamma (IFN-gamma) on rat islet cells in monolayer culture. We here demonstrate that (a) IFN-gamma, but not IL-1 or TNF, can sensitize islet cells to subsequent cytolysis by other cytokines (IL-1 or TNF); (b) the cytolytic effect of sequential addition of IFN-gamma, then IL-1 or TNF (approximately 35 40% 51Cr release) is similar to that produced by the concurrent addition of IFN gamma plus IL-1 or TNF; (c) the priming effect of IFN-gamma persists for 3 to 6 or more days after its removal; and (d) islet cells preincubated with IFN-gamma are also more sensitive to cytolysis by splenic mononuclear cells from diabetes prone BB/Wor rats. These findings suggest that IFN-gamma produced by activated T lymphocytes and monocytic cells infiltrating islets in Type 1 diabetes may play a direct and important role in sensitizing beta cells to damage by other cytokines (IL-1, TNF) and cytotoxic cells in the immune/inflammatory infiltrate. PMID- 2111139 TI - On factors that regulate growth of transplanted islets. PMID- 2111140 TI - Effect of lysine modification on the secondary structure of ovalbumin. AB - In order to determine the effect of chemical modification of the epsilon-amino groups on the secondary structure of ovalbumin, we prepared six acetylated (17, 36, 54, 70, 82, and 98%) and four succinylated derivatives (25, 50, 72, and 97%) of the protein. Native ovalbumin and the acylated derivatives were homogeneous as revealed by the electrophoretic pattern. The UV-absorption and fluorescence spectra changed progressively with the extent of modification. However, circular dichroic (CD) studies indicated that acylation of 15 of the 20 lysine residues had little effect on the secondary structure of ovalbumin. Acylation of the remaining five lysine residues resulted in a fairly severe change in the secondary structure. The alpha-helical content decreased from about 31% in the native state to 16.5% in the 97% succinylated ovalbumin and to 21.5% in the 98% acetylated derivative. A comparison of these data with the spectral and hydrodynamic data of Qasim and Salahuddin (1978) suggested that the secondary structure of ovalbumin is more resistant to acylation than is the tertiary structure and, thus, the tertiary and the secondary structures are, to some extent, mutually independent. Raising the pH to 11.2 did not alter the secondary structure of ovalbumin and increasing the ionic strength by more than 20-fold did not reverse the loss of helical structure in 97% succinylated protein. These two observations suggest that the change in secondary structure upon maximal acylation may not only involve electrostatic effects, but also certain other factors, such as steric hindrance due to the entering bulky groups. PMID- 2111141 TI - Design and production of customized field shaping devices for electron arc therapy. AB - A key element in the implementation of electron arc therapy is the use of customized field shaping devices on or near the patient's surface to protect normal tissue surrounding the treatment surface. Techniques for design and production of field shaping devices have evolved to meet the requirements of improved efficiency, patient comfort and protection, and reproducibility of patient set-up. Techniques in current use at the University of Utah are described and illustrated. PMID- 2111142 TI - Selection of recombinant vaccinia viruses (Tian Tan strain) expressing hepatitis B virus surface antigen by using beta-galactosidase as a marker. AB - We constructed a plasmid that contains a small piece of DNA with two vaccinia promoters running in opposite directions--a promoter from a late gene encoding an 11 K polypeptide (P11) and a promoter from an early gene encoding 25K (P25). These promoters were isolated from the Tian Tan strain of vaccinia virus and were flanked by the thymidine kinase (TK) sequence of the same virus. Genes encoding the hepatitis B virus surface antigen (HBsAg) and the Escherichia coli beta galactosidase (LacZ) were inserted downstream of the 11 K and 25 K promoters respectively so that coexpression plasmids were constructed. Recombinant vaccinia viruses were selected directly by picking blue plaques formed under overlaying agarose medium containing X-gal. HBsAg was expressed to high level by these recombinant viruses. These recombinant viruses showed reduced virulence on rabbit skin and induced anti-HBs after intradermal inoculation of rabbits. PMID- 2111143 TI - Cloning and prokaryotic expression of a biologically active human placental aldose reductase. AB - cDNA clones coding for human aldose reductase (AR) were isolated by antibody screening of a placental lambda gt11 cDNA library. The cDNA comprises the entire coding region and has a total length of 1,394 bp. The sequence deduced from the open reading frame encodes a protein of 316 amino acids and its amino acid composition is identical to the placental protein 9 (PP9), whose isolation and characterization were described by Bohn et al. (1982). The amino acid sequence of the placental human AR shows high homology to the rat AR; both proteins belong to the same protein superfamily as human liver AR, frog lens rho-crystallin, and bovine lung prostaglandin F synthase. Northern blot hybridization analysis revealed a size for the AR mRNA of approximately 1,500 bases. In addition to the full-length cDNA, one lambda gt11 clone was isolated which carries a putative intron of 597 bp at nucleotide position 754, corresponding to amino acid position 247. Expression of the AR cDNA in Escherichia coli resulted in the synthesis of a protein with a molecular weight of approximately 35 kD which can be immunoprecipitated specifically with antiserum raised against PP9. Despite the absence of a typical signal sequence, the human aldose reductase is partially translocated into the periplasm of the E. coli cells, where it is present in an enzymatically active form. PMID- 2111144 TI - Biosynthesis and secretion of M- and Z-type alpha 1-proteinase inhibitor by human monocytes. Effect of inhibitors of glycosylation and of oligosaccharide processing on secretion and function. AB - The biosynthesis and secretion of M-type and Z-type alpha 1-antitrypsin was studied in human monocytes. In monocytes of PiMM individuals alpha 1-antitrypsin represented 0.08% of the newly synthesized proteins and 0.44% of the secreted proteins. Two molecular forms of alpha 1-antitrypsin could be identified: a 51 kDa intracellular form, susceptible to endoglucosaminidase H, thus representing the high-mannose type precursor form and a 56-kDa form resistant to endoglucosaminidase H which was secreted into the medium. Inhibition of de novo glycosylation by tunicamycin impaired the secretion of M-type alpha 1-antitrypsin by about 75% whereas inhibition of oligosaccharide processing by the mannosidase II inhibitor swainsonine did not alter the secretion of M-type alpha 1 antitrypsin. alpha 1-Antitrypsin secreted by human monocytes was functionally active as measured by complex formation with porcine pancreatic elastase. Even unglycosylated alpha 1-antitrypsin secreted by human monocytes treated with tunicamycin formed a complex with elastase. In monocytes of PiZZ individuals the secretion of alpha 1-antitrypsin was decreased. 72% of newly synthesized M-type alpha 1-antitrypsin, but only 35% of newly synthesized Z-type alpha 1-antitrypsin were secreted during a labeling period of 3 h with [35S]methionine. The 51-kDa form of Z-type alpha 1-antitrypsin accumulated intracellularly, whereas the 56 kDa form was secreted. Inhibition of oligosaccharide processing by swainsonine did not alter the decreased secretion of Z-type alpha 1-antitrypsin, whereas inhibition of de novo glycosylation by tunicamycin blocked the secretion of Z type alpha 1-antitrypsin completely. PMID- 2111146 TI - Is sperminogen a modified proacrosin? Isolation, purification, and partial characterization of low-molecular-mass boar proacrosin. AB - Low-molecular-mass zymogen was extracted from boar spermatozoa together with proacrosin using 10% acetic acid supplemented with 10% glycerol, and was purified by the sequential use of gel filtration on Sephadex G-75 and (FPLC) reversed phase chromatography. LMM zymogen represented approximately 5% of the latent trypsin-like activity present in the sperm extract. SDS-PAGE indicated a molecular mass of 33 kDa. The zymogen reacted with both mouse monoclonal and rabbit polyclonal antibodies to boar acrosin. Determination of the N-terminal sequence of 34 amino-acid residues revealed its identity with the known N terminal sequence of boar proacrosin. PMID- 2111145 TI - Evolution of a group of transposed human V kappa genes. AB - Eleven V kappa genes within a genomic region which has been transposed from the short to the long arm of chromosome 2 have been characterized by sequence analyses. Nine of the analysed genes exist within the genome in three highly homologous copies each. Sequence comparisons of the triplicated genes make it very likely that the three copies of a given gene were produced at different times during evolution. A chain of events which led to a stepwise amplification of precursor genes is discussed. PMID- 2111147 TI - The 3'-flanking region shared by the human apolipoprotein AI and CIII gene regulates gene expression in cooperation with 5'-flanking elements. AB - The genes of the apolipoproteins AI and CIII are localized in opposite orientation on chromosome 11 in close vicinity, separated from each other by a non-coding intergenic region of 2.1 kb. The interdependence of their expression has been studied in cotransfection experiments in Hep G2 cells. An expression vector harboring the intergenic region with CAT as reporter gene and likewise pUC 19 derivatives with the putative cis-elements were constructed. Inhibition of gene expression by 5'-flanking elements of the apo AI and CIII gene was observed. Four proteins have been identified in nuclear extracts of Hep G2 cells that bind to several sequences of the intergenic domain but not to the 5'-flanking regions of apo AI or CIII gene. These proteins might be responsible for the silencer effect. The pathway of the regulation of apo CIII and AI expression derived from the experiments described here is supported by mutations in the intergenic region, leading to the phenotype of hypertriglyceridemia, and the stimulatory effect of cholesterol on apo AI transcription in Hep G2 cells. PMID- 2111148 TI - Somehow we have to stop the train wreck. Part 1. PMID- 2111149 TI - Hospital readmissions, otolaryngology, and the diagnosis related group hospital payment system. AB - An analysis of otolaryngologic patients requiring readmission was conducted at our institution during a 4-year period to determine the number of readmissions per patient and the time between discharge and hospital readmission. Readmitted otolaryngologic patients were found to have had greater hospital resource utilization, financial risk under diagnosis-related group payment, and mortality, compared with those patients not readmitted to our facility. For patients readmitted to otolaryngologic services (21.2% of total otolaryngologic patients), 20.4% of the readmissions occurred within 30 days of hospital discharge. Of these, 39.3% required one hospital readmission, 16.3% required two readmissions, and 46.4% of the patients called for three or more hospital admissions. Clinical factors were identified that resulted in a greater incidence of otolaryngologic readmission. Otolaryngologic patients readmitted to other clinical services were also studied. This analysis loads to the conclusion that inequities exist within the diagnosis related group hospital payment system vis-a-vis otolaryngologic readmissions. The results of these data also demonstrate leverage points in which we will be able to focus outpatient services for otolaryngologic patients requiring readmission and potentially decrease inpatient hospital expenditures in the days ahead. PMID- 2111150 TI - Percutaneous endoscopic gastrostomy as a standard procedure in head and neck surgery. AB - Adequate nutritional support is essential in patients with head and neck cancer, especially if extended oropharyngeal surgery is indicated. Enteral nutrition is an effective and safe alternative to parenteral nutrition, but the use of nasogastric tubes has several disadvantages in these patients. We describe our experience with percutaneous endoscopic gastrostomy as a standard procedure prior to surgical resection in patients with head and neck cancer. PMID- 2111151 TI - Basic mechanisms of focal epilepsies. PMID- 2111152 TI - The effect of continued feeding of physiological amounts of lactose on the level of intestinal lactase and other disaccharidase enzyme activities in the rat. AB - Intestinal lactase activity in mammals is high at birth but begins to decline around weaning and reaches very low levels in adult life. The triggering mechanism for this decline is not clear. Because of the association of the decline with weaning, lack of lactose in the diet has been implicated. In 110 growing rats, the effect of continued supplementation of the diet after weaning with physiological amounts of either cows' milk or a 5% lactose solution on intestinal lactase and other disaccharidase enzyme activities was investigated. In both control and test animals, the specific lactase activity decreased from a peak value of 115 +/- 4 mumol min-1 g-1 protein before weaning to about 10% at maturity. There was no significant difference in the level or the pattern of decline between the groups. Sucrase, maltase and trehalase showed the normal maturational changes without being affected by the test diets. The finding suggests that diet, particularly the presence or absence of physiological amounts of lactose, has no appreciable effect on the age related spontaneous decline of intestinal lactase activity or on the pattern of development of the other disaccharidases. PMID- 2111153 TI - The responses of superior laryngeal nerve afferent fibres to laryngeal airway CO2 concentration in the anaesthetized cat. AB - In anaesthetized cats, the isolated, in situ, larynx was subjected to a simulated respiratory cycle and the responses of fifty-six superior laryngeal nerve (SLN) afferent fibres to respiration-related stimuli were examined during changes in the fractional CO2 concentration of the laryngeal airway (Faw, CO2). Sensory SLN fibres which displayed low rates of discharge when the larynx was unventilated (quiescent fibres) and which responded to negative laryngeal airway pressure were excited by elevations in Faw, CO2 whereas quiescent fibres responsive to positive laryngeal pressure were inhibited by the same procedure. We propose that changes in airway CO2 levels may play a role in maintaining upper airway patency, especially during sleep. PMID- 2111154 TI - The effects of changes in laryngeal airway CO2 concentration on genioglossus muscle activity in the anaesthetized cat. AB - In the anaesthetized cat the larynx was isolated in situ, artificially ventilated and used to assess reflex effects exerted by respiration-related laryngeal stimuli on genioglossus electromyographic activity (Gg EMG) and respiratory frequency (RF). Phasic Gg EMG was not observed when the larynx was unventilated but was evoked, with a concurrent decrease in RF, when negative pressures or oscillatory pressures similar to those of normal ventilation were applied to the larynx. Increases in laryngeal airway CO2 concentration also enhanced Gg EMG and reduced RF. All reflex effects were abolished by bilateral section of the superior laryngeal nerves. We propose that negative intralaryngeal pressure and CO2 may act together to restore pharyngeal patency during obstructive apnoea. PMID- 2111155 TI - Localization of the murine leukemia inhibitory factor gene near the centromere on chromosome 11. AB - Leukemia inhibitory factor (LIF) is a glycoprotein with divergent activities: It induces the differentiation of certain myeloid leukemic cells, inhibits the differentiation of embryonic stem cells, and promotes bone remodelling in vivo and in vitro. The murine LIF gene has been assigned to the proximal region of chromosome 11 at sub-bands A1-A2, by analysis of a panel of mouse x Chinese hamster somatic cell hybrids and by in situ hybridization. Interestingly, the proximal portion of chromosome 11 has been shown, by virtue of its parental origin effects, to contain gene(s) involved in fetal growth. It is also interesting that there is a preponderance of chromosome 11 abnormalities in embryonal carcinoma cells. The localization of the murine LIF gene confirms the homology of a portion of murine chromosome 11 with human chromosome 22q, the site of the human LIF gene. PMID- 2111156 TI - Zolpidem intoxication mimicking narcotic overdose: response to flumazenil. AB - Zolpidem is a recently introduced sleep-inducer which is thought to act on the central-type benzodiazepine receptors. This observation is the first report of drug poisoning with this compound. The toxic response was characterized by the development of a profound but short-lasting coma, associated with pin-point pupils and respiratory depression, as observed in a narcotic overdose. These clinical signs were not influenced by the administration of naloxone, but responded dramatically to flumazenil. Some analytical data on zolpidem toxicokinetics are presented. PMID- 2111157 TI - Human brain sulphotransferase and glucuronyltransferase. AB - The activities of cytosolic sulphotransferase (ST) and microsomal glucuronyltransferase (GT) were measured with 1-naphthol as the substrate in three frontal cortex, three temporal cortex, one parietal cortex, one occipital cortex and two cerebellar cortex specimens from human brain. The average activity was 11.7 +/- 4.2 pmol/min/mg protein/(ST) and 26.8 +/- 13.6 pmol/min/mg protein (GT). The kinetics of ST were studied varying the concentration of 1-naphthol in five brain specimens (temporal cortex, temporal subcortex, occipital cortex, cerebellum cortex and frontal cortex) whereas those of GT were studied in a sample obtained by pooling the microsomal fractions from the following eight brain tissues: one frontal cortex, four temporal cortex, one parietal cortex and two cerebellar cortex specimens. The Km of the first and second enzyme was 1.55 +/- 0.47 microM (mean +/- s.d.) and 121 microM, respectively. The Vmax values were 13.70 +/- 8.16 (mean +/- s.d.) pmol/min/mg protein (ST) and 103 pmol/min/mg protein (GT). Vmax/Km was ten times higher for ST than GT. These data suggest that ST is the predominant pathway at low concentrations of 1-naphthol whereas at higher concentrations, GT becomes the predominant pathway. PMID- 2111158 TI - Occupational cadmium exposure and testicular endocrine function. AB - Cadmium is known to cause testicular necrosis in several animal species, although there is little data on its possible effects in humans. We have investigated the effect of occupational cadmium exposure on the pituitary-testicular endocrine axis, as measured by serum testosterone, luteinizing hormone (LH) and follicular stimulating hormone (FSH), in a well-characterized population occupationally exposed to cadmium. Over 60% of all workers, who had been exposed to cadmium oxide fumes for longer than a year, in a single factory, since 1926, were studied. Integrated cadmium exposure estimates were constructed for each subject from atmospheric measurements, together with other available company data, and these exposure estimates were validated by in-vivo neutron activation analyses of liver cadmium burdens. The lack of testicular endocrine effects was in contrast to significant dose-related changes in renal glomerular and tubular function demonstrated in the same population. PMID- 2111159 TI - Muramyl dipeptide inhibits replication of human immunodeficiency virus in vitro. AB - In the search for compounds capable of inducing endogenous production of colony stimulating factor (CSF) and possessing activity against human immunodeficiency virus (HIV), an immunomodulator, muramyl dipeptide (MDP), was investigated. MDP can enhance monocyte-macrophage CSF in serum and promote nonspecific resistance against a variety of microbial pathogens. MDP exhibited an inhibitory activity against HIV infection of CD4+ H9 lymphocytes and U937 monocytoid cells. An inhibitor of viral reverse transcriptase, 2', 3'-dideoxyadenosine, produced potent inhibition in cultures which were similarly infected with HIV. MDP could partially reduce antigen production in persistently HIV-infected KE37/1 lymphocyte cultures. PMID- 2111160 TI - Prognostic significance of quantitative levels of HIV p24 binding capacity in HIV infection. AB - Human immunodeficiency virus, type 1 (HIV-1), produces a chronic infection with a long latency before clinical disease. We followed 214 untreated subjects for 12 42 months to study the natural history of HIV infection: 110 were classified as asymptomatic, 11 as AIDS-related complex (ARC), 15 as AIDS with Kaposi's sarcoma (KS), 31 as AIDS with opportunistic infections (AIDS/OI), and 47 were HIV seronegative controls. The quantitative capacity of serum to complex HIV p24 antigen, termed the p24 binding capacity (p24 BC), and quantitative levels of HIV p24 antigen in serum were determined at regular intervals. For people in all diagnostic groups, a p24 BC below 31 ng/ml was more closely associated with progression to AIDS/OI than was p24 antigen positivity; 94% of AIDS/OI, 86% of ARC, 56% of AIDS/KS, and 19% of asymptomatic subjects had p24 BC less than 31 ng/ml during the study period, while 67% of AIDS/OI, 27% of ARC, 61% of AIDS/KS, and 20% of asymptomatic subjects were p24 antigenemic. Prospective analysis of 47 asymptomatic seropositive men followed for 3 years, who showed actuarial progression rates to ARC at 4%, 13%, and 23% and to AIDS at 5%, 8%, and 8% at 1, 2, and 3 years, indicated that entry levels of p24 BC below 31 ng/ml were as strongly associated with progression to ARC/AIDS as was p24 antigenemia (p = 0.0003 vs. p = 0.008). The p24 binding capacity assay is a new and convenient methodology to measure immunocomplexing antibody to HIV p24 and is a powerful indicator of progressive HIV disease. PMID- 2111161 TI - Discrimination of HIV-2 infection from HIV-1 infection by western blot and radioimmunoprecipitation analysis. AB - Serum and plasma samples were collected from blood donors who were confirmed positive for antibodies to HIV-1 in the United States, and from blood donors and individuals in West Africa and Portugal who were positive for antibodies to HIV 1, HIV-2, or both. Western blots and sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) radioimmunoprecipitation assays (RIPA) utilizing native HIV-1 and HIV-2 proteins were performed on these specimens to determine the ability of these procedures to discriminate between HIV-1 and HIV-2 infections. Extensive serologic cross reactivity between HIV-1 and HIV-2 p24 was found in both populations. Antibody reactivity to the envelope protein gp120 was able to discriminate 20 of 20 (100%) U.S. specimens as HIV-1 infections. In specimens from West Africa and Portugal, Western blot and RIPA were in complete agreement on 33 of 42 samples (78.6%). Among these 33 specimens, 10 were found to be reactive for antibodies to HIV-1 only, 10 were reactive to HIV-2 only, and 13 were considered to be dually reactive, having antibodies reactive with both HIV-1 gp120 and HIV-2 gp120. Nine of the 42 specimens were discordant by Western blot and RIPA classification, being dually reactive by one procedure and reactive with only one viral gp120 by the other technique. Because of the serological cross reactivities between HIV-1 and HIV-2, in certain populations it is difficult to ascertain whether an individual is infected with HIV-1, HIV-2, a new viral type, or whether the individual is infected simultaneously with multiple viruses. More specific tests such as viral isolation or molecular probes may be necessary to distinguish between infections with these viruses in certain populations. PMID- 2111162 TI - Interactions of serum proteins with small unilamellar liposomes composed of dioleoylphosphatidylethanolamine and oleic acid: high-density lipoprotein, apolipoprotein A1, and amphipathic peptides stabilize liposomes. AB - Small unilamellar liposomes composed to dioleoylphosphatidylethanolamine (DOPE) and oleic acid (OA) are stabilized by incubation with normal human serum or plasma [Liu, D., & Huang, L. (1989) Biochemistry 28, 7700-7707]. The present report describes a systematic study of interactions of purified serum proteins and lipoproteins with these liposomes. Albumin destabilized liposomes by extracting OA from the liposomes, whereas immunoglobulins and lipoproteins (HDL, LDL, and VLDL) had no effect. However, HDL and, to some extent, VLDL showed a rapid stabilization activity against the lytic effect of albumin. HDL added together with or shortly after the addition of albumin completely abolished the liposome leakage and aggregation effects induced by albumin. SDS-PAGE analysis of the HDL-stabilized liposomes revealed that apolipoprotein A1 was associated with liposomes. Purified apolipoprotein A1, but not a lipid mixture resembling the lipid composition of HDL, showed comparable liposome stabilization activity as HDL. Furthermore, synthetic peptides resembling the amphipathic helices found in apolipoprotein A1 also showed strong liposome stabilization activity. Peptides which were able to form amphipathic helixes of a wedge shape were more effective stabilizers than those which could not. These data indicate that HDL plays a major role in human serum or plasma for the liposome stabilization activity. HDL exerts its activity probably by the interactions of the amphipathic helices of apolipoprotein A1 with the hydrophobic voids found on the outer surface of the highly curved, small liposomes. PMID- 2111163 TI - Glucosamine-6-phosphate synthase from Escherichia coli: determination of the mechanism of inactivation by N3-fumaroyl-L-2,3-diaminopropionic derivatives. AB - A mechanistic investigation of the inactivation of Escherichia coli glucosamine-6 phosphate synthase by N3-(4-methoxyfumaroyl)-L-2,3-diaminopropionate (FMDP) was undertaken. On the basis of the known participation of the N-terminal cysteine residue in this process [Chmara et al. (1986) Biochim. Biophys. Acta 870, 357; Badet et al. (1988) Biochemistry 27, 2282], the model reactions between FMDP and L-cysteine and between FMDP and the synthetic decapeptide Cys-Gly-Ile-Val-Gly-Ala Ile-Ala-Gln-Arg, corresponding to the amino-terminal protein sequence, were studied. The results allowed us to propose a pathway that is in perfect agreement with the biochemical results: enzyme inactivation arose from Michael addition of glutamine binding site cysteine-1 on the fumaroyl double bond at the beta position of the ester group. Upon denaturation under slightly alkaline conditions, this adduct underwent cyclization to a transient succinimide adduct, which rearranged into the stable 2-substituted 1,4-thiazin-3-one-5-carboxylate involving participation of the cysteine amino group. The tryptic radiolabeled peptides purified from [3H]FMDP-treated enzyme and resistant to Edman degradation coeluted with the products resulting from the model reaction between the synthetic decapeptide and the inhibitor. PMID- 2111164 TI - Kinetic and conformational effects of lysine substitutions for arginines 35 and 87 in the active site of staphylococcal nuclease. AB - The high-resolution X-ray crystal structure of staphylococcal nuclease (SNase) suggests that the guanidinium groups of Arg 35 and Arg 87 participate as electrophilic catalysts in the attack of water on the substrate phosphodiester. Both arginine residues have been replaced with "conservative" lysine residues so that both the importance of these residues in catalysis and the effect of changes in electrostatic interactions on active site conformation can be assessed. The catalytic efficiencies of R35K and R87K are decreased by factors of 10(4) and 10(5) relative to wild-type SNase, with R87K showing a very significant reduction in its affinity for both DNA substrate and the competitive inhibitor thymidine 3',5'-bisphosphate (pdTp). The thermal denaturation behavior of both mutant enzymes differs from that of wild type both in the absence and in the presence of the active site ligands Ca2+ and pdTp. Both the 1H NMR chemical shifts and interresidue nuclear Overhauser effects (NOEs) of residues previously assigned to be in the hydrophobic core of SNase are altered in R35K and R87K. These observations, similar to those recently reported by our laboratories for substitutions for Glu 43 [Hibler, D. W., Stolowich, N. J., Reynolds, M. A., Gerlt, J. A., Wilde, J. A., & Bolton, P. H. (1987) Biochemistry 26, 6278; Wilde, J. A., Bolton, P. H., Dell'Acqua, M., Hibler, D. W., Pourmotabbed, T., & Gerlt, J. A. (1988) Biochemistry 27, 4127], suggest that lysine substitutions are not conservative in SNase and disrupt the conformation of the active site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111166 TI - Characterization of interleukin 2 stimulated 65-kilodalton phosphoprotein in human T cells. AB - We have characterized the cellular proteins which are rapidly phosphorylated by interleukin 2 (IL 2) in a human IL 2 dependent cell line. When treated with IL 2, the phosphorylation of five proteins, 65, 50, 37, 24, and 21 kDa, was found in IL 2 dependent cell lines by two-dimensional gel electrophoretic analysis. After cell conversion from an IL 2 dependent state to an IL 2 independent state, one of the five phosphoproteins, the 65-kDa protein, became constitutively phosphorylated even without addition of IL 2. Also, in other IL 2 independent cell lines, such as KUT-2 and HUT-102, constitutive phosphorylation of the 65-kDa protein occurred without IL 2-stimulation. So our researchers were focused on biochemical characterization of the 65-kDa protein. It was found that the 65-kDa protein was one of the major cellular proteins by comparing the results of two dimensional gel electrophoretic analysis of [32P]Pi-labeled and [3H]leucine labeled cellular proteins and peptide mapping analysis. Subcellular fractionation studies indicated that the 65-kDa protein is a cytosol protein. The 65-kDa protein was purified from cytosol of a human T cell line, and its amino acid composition and amino acid sequences of its three oligopeptides were determined. It was found that the 65-kDa protein is identical with 1-plastin. PMID- 2111165 TI - Function of serine-171 in domain closure, cooperativity, and catalysis in Escherichia coli aspartate transcarbamoylase. AB - Structural studies of Escherichia coli aspartate transcarbamoylase suggest that the R state of the enzyme is stabilized by an interaction between Ser-171 of the aspartate domain and both the backbone carbonyl of His-134 and the side chain of Gln-133 of the carbamoyl phosphate domain of a catalytic chain [Ke, H.-M., Lipscomb, W.N., Cho, Y., & Honzatko, R. B. (1988) J. Mol. Biol. 204, 725-747]. In the present study, site-specific mutagenesis is used to replace Ser-171 by alanine, thereby eliminating the interactions between Ser-171 and both Gln-133 and His-134. The Ser-171----Ala holoenzyme exhibits no cooperativity, more than a 140-fold loss of activity, little change in the carbamoyl phosphate concentration at half the maximal observed specific activity, and a 7-fold increase in the aspartate concentration at half the maximal observed specific activity. Although the Ser-171----Ala enzyme exhibits no homotropic cooperativity, it is still activated by N-(phosphonacetyl)-L-aspartate (PALA), but not by succinate, in the presence of saturating carbamoyl phosphate and subsaturating aspartate. At subsaturating concentrations of aspartate, the Ser-171----Ala enzyme is still activated by ATP but is inhibited less by CTP than is the wild-type enzyme. At saturating concentrations of aspartate, the Ser-171----Ala enzyme is activated by ATP and inhibited by CTP to an even greater extent than at subsaturating concentrations of aspartate. At saturating aspartate, the wild-type enzyme is neither activated by ATP nor inhibited by CTP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111167 TI - Mechanism of activation of cholera toxin by ADP-ribosylation factor (ARF): both low- and high-affinity interactions of ARF with guanine nucleotides promote toxin activation. AB - Activation of adenylyl cyclase by cholera toxin A subunit (CT-A) results from the ADP-ribosylation of the stimulatory guanine nucleotide binding protein (GS alpha). This process requires GTP and an endogenous guanine nucleotide binding protein known as ADP-ribosylation factor (ARF). One membrane (mARF) and two soluble forms (sARF I and sARF II) of ARF have been purified from bovine brain. Because the conditions reported to enhance the binding of guanine nucleotides by ARF differ from those observed to promote optimal activity, we sought to characterize the determinants influencing the functional interaction of guanine nucleotides with ARF. High-affinity GTP binding by sARF II (apparent KD of approximately 70 nM) required Mg2+, DMPC, and sodium cholate. sARF II, in DMPC/cholate, also enhanced CT-A ADP-ribosyltransferase activity (apparent EC50 for GTP of approximately 50 nM), although there was a delay before achievement of a maximal rate of sARF II stimulated toxin activity. The delay was abolished by incubation of sARF II with GTP at 30 degrees C before initiation of the assay. In contrast, a maximal rate of activation of toxin by sARF II, in 0.003% SDS, occurred without delay (apparent EC50 for GTP of approximately 5 microM). High affinity GTP binding by sARF II was not detectable in SDS. Enhancement of CT-A ADP-ribosyltransferase activity by sARF II, therefore, can occur under conditions in which sARF II exhibits either a relatively low affinity or a relatively high affinity for GTP. The interaction of GTP with ARF under these conditions may reflect ways in which intracellular membrane and cytosolic environments modulate GTP-mediated activation of ARF. PMID- 2111168 TI - Positional independence and additivity of amino acid replacements on helix stability in monomeric peptides. AB - The 17-residue peptide acetylAEAAAKEAAAKEAAAKAamide, described as an autonomous folding unit (Marqusee & Baldwin, 1987), has been used to examine the effect of amino acid replacements on helix stability. Alanine residues(s) at positions 4, 9, and 14 in the peptide sequence were replaced either singly or multiply by either serine or methionine residues with solid-phase peptide synthesis. The thermal dependence of the helix/coil transition of each peptide was observed by far-ultraviolet circular dichroism. Within experimental variation, all three single replacements exhibit a common thermal transition, and all three double replacements exhibit a different common thermal transition. These results suggest that replacement of the central alanine residue in the repeat EAAAK located in the N-terminus, in the middle, or in the C-terminus of the peptide helix has the same effect on helix stability. The melting temperature of each thermal transition was estimated by assuming a linear van't Hoff plot and a change in molar ellipticity of 33,500 deg cm2 dmol-1. Such analysis indicates that each replacement of an alanine residue by a serine residue diminishes the melting temperature by 11 +/- 1 degrees C and that each replacement of an alanine residue by a methionine residue diminishes the melting temperature by 6 +/- 1 degrees C. These results suggest that the effect of these replacements on helix stability is additive. PMID- 2111169 TI - Determinants of visual pigment absorbance: role of charged amino acids in the putative transmembrane segments. AB - I have investigated the effect on bovine rhodopsin's absorbance spectrum of charged amino acid changes in the putative membrane-spanning regions. A total of 14 site-directed mutants were constructed at 6 amino acid positions: 83, 86, 122, 134, 135, and 211. Two of these positions are occupied by charged amino acids that are conserved in all four human visual pigments (positions 134 and 135). In the four variable positions, single and double mutants were constructed to reproduce the intramembrane distribution of charged amino acids predicted for each human cone pigment. Following solubilization in digitonin and reconstitution with 11-cis-retinal, the photobleaching difference spectrum of each pigment was determined in the presence of hydroxylamine. The absorbance spectra of the mutant pigments are all surprisingly close to that of native bovine rhodopsin (lambda max = 498 nm), ruling out a significant role for these residues in spectral tuning. PMID- 2111170 TI - Zinc binding and its trapping by allosteric transition in glucosamine-6-phosphate deaminase from Escherichia coli. AB - Glucosamine-6-phosphate isomerase deaminase from Escherichia coli, a typical allosteric enzyme, becomes less cooperative and 50% inhibited when treated with zinc. This metal cation behaving as a tight-bound and slow partial inhibitor. Modification of a pair of vicinal reactive thiols with some sulfhydryl reagents mimics this effect. On the other hand, sulfhydryl reactivity disappears in the presence of saturating concentrations of Zn2+, which does not modify the kinetics of S-methylated enzyme, a finding that indicates that vicinal thiols are an essential part of the zinc-binding site. Allosteric activation of the deaminase causes trapping of the metal, which cannot be released by dialysis against a buffer containing EDTA. Cadmium and nickel(II) cations also produce a similar effect. PMID- 2111171 TI - Conformational study of the chromosomal protein MC1 from the archaebacterium Methanosarcina barkeri. AB - Methanogen chromosomal protein MC1 is a polypeptide of 93 amino acid residues (Mr 10,757) which represents the major protein associated with the DNA of the archaebacterium Methanosarcina barkeri and can protect DNA against thermal denaturation. The conformation of protein MC1 has been investigated by means of predictive methods, infrared spectroscopy, circular dichroism and tryptophan fluorescence studies. Protein MC1 has a low amount of alpha-helix but contains antiparallel beta-sheet strands. The larger hydrophobic cluster which contains tryptophan at position 61 appears buried in the protein. Addition of salts induces the unfolding of the protein and makes the tryptophan indole ring more rigid. With respect to its primary structure and its conformation, protein MC1 appears radically different from the chromosomal DNA-binding protein II (also called HU-type protein) in eubacteria. PMID- 2111172 TI - Feedback regulation of platelet function by 12S-hydroxyeicosatetraenoic acid: inhibition of arachidonic acid liberation from phospholipids. AB - We have proposed a mechanism that platelet aggregation is regulated by its 12 lipoxygenase product, 12S-hydroxyeicosatetraenoic acid (12-HETE) (Sekiya, F., Takagi, J. and Saito, Y. (1989) Thrombos. Res. 56, 407-415). Inhibition of endogenous 12-HETE production by 15-HETE, a specific inhibitor of 12 lipoxygenase, accelerated aggregation of bovine platelets in response to collagen and arachidonic acid liberation from phospholipids was enhanced. Exogenously added 12-HETE suppressed collagen-induced liberation of arachidonic acid and the aggregation was also inhibited. On the other hand, 12-HETE did not interfere with thromboxane synthesis from free arachidonic acid in a cell-free system. These observations suggest that 12-HETE exerts a negative feedback to prevent excess aggregation through interference with arachidonic acid liberation from membrane phospholipids. PMID- 2111174 TI - Effective use of rabbit gastric antral mucosal slices in prostaglandin synthesis and metabolism studies. AB - Intact slice preparations of rabbit stomach (antral mucosa, corporal mucosa, antral muscle and corporal muscle) were incubated and the released prostaglandins (PGs) were measured by reverse-phase high-performance liquid chromatography using 9-anthryldiazomethane for derivatization. With respect to total PG production, the highest amounts were generated by antral mucosal slices. Antral mucosal slices produced PGE2, 6-keto PGF1 alpha, thromboxane B2, PGF2 alpha and PGD2 (in descending order of magnitude) and possessed a high capacity for producing 13,14 dihydro-15-keto derivatives of both PGE2 and PGF2 alpha. Studies utilizing aspirin, EGTA or Ca2+ revealed that PG release by antral mucosal slices in the present in vitro system reflects a composite of the activities of phospholipase A3, PG cyclooxygenase and PG-metabolizing enzymes. These results show that antral mucosal slices will be useful in physiological and pharmacological studies on PG synthesis and metabolism of the stomach. PMID- 2111173 TI - Evidence in vitro that hepatic lipase reduces the concentration of apolipoprotein A-I in rabbit high-density lipoproteins. AB - Incubation of rabbit plasma in vitro with hepatic lipase resulted in the hydrolysis of triacylglycerol in high-density lipoproteins (HDL) and a reduction in HDL particle size. These changes were accompanied by a decrease in the concentration of apolipoprotein A-I (apo A-I) in the HDL. The loss of apo A-I was demonstrated independently by ultracentrifugation, size exclusion chromatography and gradient gel-immunoblot analysis. It was unrelated to hydrolysis of HDL phospholipids but did correlate with the reduction in HDL particle size. These studies suggest that the concentration of apo A-I in HDL may be influenced by factors which regulate the metabolism of HDL core lipid constituents. PMID- 2111175 TI - Identification of the calmodulin binding domain of alpha-fodrin and implications for folding. AB - A cDNA clone producing a protein that binds calmodulin has been isolated from a mouse macrophage library. The cDNA was sequenced and identified as coding for fodrin. By deleting part of the sequence, the calmodulin binding domain was located. The site is situated on repeat 11 of fodrin probably on its extra arm. This part of the sequence exhibits great similarity to other calmodulin binding proteins. Analysis of the sequence and spatial structure of calmodulin revealed a domain which is quite complementary to the sequence identified on fodrin. These results provide a new insight into the structure of fodrin and consequently into the structure of proteins of the spectrin family. A model for the general folding of these molecules is proposed, involving a simple three-layer folding. The structure was further corroborated by analysis of charge distribution in the vicinity of the calmodulin binding site. The folding we propose is in good agreement with digestion experiments and explains observations in diseases resulting from mutations of human spectrin. PMID- 2111176 TI - Enzymatic properties, renaturation and metabolic role of mannitol-1-phosphate dehydrogenase from Escherichia coli. AB - Enzymatic properties, renaturation and metabolic role of mannitol-1-phosphate dehydrogenase from Escherichia coli. D-mannitol-1-phosphate dehydrogenase was purified to homogeneity from Escherichia coli, and its physicochemical and enzymatic properties were investigated. The molecular weight of the polypeptide chain is 45,000 as determined by polyacrylamide gel electrophoresis in denaturing conditions. High performance size exclusion chromatography gives an apparent molecular weight of 47,000 for the native enzyme, showing that D-mannitol-1 phosphate dehydrogenase is a monomeric NAD-dependent dehydrogenase. D-mannitol-1 phosphate dehydrogenase is rapidly denatured by 6 M guanidine hydrochloride. Non superimposable transition curves for the loss of activity and the changes in fluorescence suggest the existence of a partially folded inactive intermediate. The protein can be fully renatured after complete unfolding, and the regain of both native fluorescence and activity occurs rapidly within a few seconds at pH 7.5 and 20 degrees C. Such a high rate of reactivation is unusual for a protein of this size. D-mannitol-1-phosphate dehydrogenase is specific for mannitol-1 phosphate (or fructose-6-phosphate) as a substrate and NAD+ (or NADH) as a cofactor. Zinc is not required for the activity. The affinity of D-mannitol-1 phosphate dehydrogenase for the reduced or oxidized form of its substrate or cofactor remains constant with pH. The affinity for NADH is 20-fold higher than for NAD+. The forward and reverse catalytic rate constants of the reaction: mannitol-1-phosphate + NAD+ in equilibrium fructose-6-phosphate + NADH have different pH dependences. The oxidation of mannitol-1-phosphate has an optimum pH of 9.5, while the reduction of fructose-6-phosphate has its maximum rate at pH 7.0. At pH values around neutrality the maximum rate of reduction of fructose-6 phosphate is much higher than that of oxidation of mannitol-1-phosphate. The enzymatic properties of isolated D-mannitol-1-phosphate dehydrogenase are discussed in relation to the role of this enzyme in the intracellular metabolism. PMID- 2111177 TI - Specific binding of vasculotropin to bovine brain capillary endothelial cells. AB - Recently, a new growth factor was purified to homogeneity; its biological activity appeared to be restricted to vascular endothelial derived cells. As it was also angiogenic in vivo, it was provisionally named vasculotropin. An iodination procedure used to label vasculotropin did not damage the molecule; it was thus possible to undertake binding studies. The binding of iodinated vasculotropin to bovine brain capillary endothelial cells reached saturation at 7 ng/ml and half maximal binding occurred at 1.5 ng/ml. Scatchard analysis of the data demonstrated 2 classes of binding sites with apparent dissociation constants of 4 and 41 pM and 600 and 4,100 sites per cell respectively. The interaction was specific since an excess of unlabelled vasculotropin, but no Fibroblast Growth Factor or Transforming Growth Factor Beta almost totally abolished the binding of the tracer. A sensitive radioreceptor-assay convenient for measuring vasculotropin in biological samples is described. PMID- 2111178 TI - Structural modifications induced by the mtDBP-C protein in the replication origin of Xenopus laevis mitochondrial DNA. AB - The structure of the non-coding region of Xenopus laevis mitochondrial DNA has been studied by electron microscopy analysis of DNA molecules end-labelled with streptavidin-ferritin. We have shown that the effect of a protein modifying the shape of the DNA double-helix can be studied and precisely located by this method. It was found that the non-coding region contains curved segments and that the mitochondrial protein mtDBP-C preferentially enhances the curvature of the promoters-replication origin region. PMID- 2111179 TI - Regulation of the immunoglobulin gene transcription. AB - The transcription of the immunoglobulin heavy (IGH), kappa (IGK) and lambda (IGL) chain genes is coordinate and B lymphocyte specific. This expression of the immunoglobulin genes is under the control of regulatory elements: the promoters located 5' of each variable (V) gene and the enhancers located between the joining and constant genes in the IGH and IGK locus and downstream on the C kappa gene. These sequences represent sites for the binding of transcription factors. A 90-100 kDa ubiquitous proteins (NF-A1) as well as two specific B cell proteins (NF-A2, OTF-2B) bind to the octamer site of the V promoter and IGH enhancer. The NF-kB protein binds to the kB site in the intron kappa enhancer, but also to kB like sites found in the promoter regions of other genes. This paper reviews the recent data on these factors and other transcription factors which bind to the promoters and enhancers of the immunoglobulin genes and control their expression. PMID- 2111181 TI - [Activation of complex I in the reaction of NADH oxidation and delta mu H+ dependent NAD+ reduction by succinate]. AB - Complex I catalyzed the NADH-oxidase and NADH-Q reductase reactions with a pH dependent lag-phase. The enzyme activated during a short-term aerobic incubation remained active for a relatively long period of time (tens of minutes at 25 degrees C). Similar NADH-induced slow changes in the activity of the reverse electron transfer were found earlier in our laboratory. The synchronous change of the enzyme activity in the forward and reverse directions points to the existence of the slowly interconverting states of complex I, namely, an active state catalyzing the NADH oxidation and delta mu H(+)-dependent NAD+ reduction and an inactive state. PMID- 2111180 TI - Characterization of DOPA decarboxylase mRNA in rat pheochromocytoma. AB - Total poly (A+) RNA has been extracted from rat pheochromocytoma and translated in vitro by means of a reticulocyte lysate system. We show that two antisera, prepared against pig kidney DOPA decarboxylase (DDC) or rat pheochromocytoma DDC, immunoprecipitate an in vitro synthetized 50 kDa polypeptide identified as DDC by competition experiments with pure DDC. The proportion of specific mRNA has been calculated and represents 0.05% of total poly A+ mRNA. Its size has been established by electrophoresis in methylmercuric hydroxide containing agarose gel, corresponding to a 2.2 kb length mRNA. PMID- 2111182 TI - [Affinity chromatography of thyroxine-binding proteins from human serum]. AB - The affinity matrix prepared by the attachment of L-thyroxine (T4) to epichlorohydrine-activated Sepharose 4B biospecifically absorbs the T4-binding globulin (TBG), 25K and 80/27K proteins, immunoglobulin G (IgG) and albumin (HSA) from human normal and retroplacental sera. The absorbed protein patterns were shown to depend on the immobilized T4 concentration, pH, temperature and incubation time. The potent eluents desorbing 85-100% of the protein are 1 mM NaOH, 3 M NH4SCN, 10(-5) M T4 or 3 mM 8-anilinonaphthalene-1-sulfonic acid (ANS) for TBG; NaOH, NH4SCN, 3 mM MgCl2 or 12mM sodium cholate for 25K protein and HSA; NaOH, NH4SCN or MgCl2 for the 80/27K and 25K proteins and IgG. Moreover, T4 desorbs small amounts (6-8%) of the 80/27K and 25K proteins, while sodium cholate elutes about 6% of TBG. The eluted from T4-Sepharose 4B and further purified TBG, 25K and 80/27K proteins display different [125I]T4-binding activities within the pH range from 2 to 9 and differ by their resistance to thermal inactivation at 50 80 degrees C. Double radial immunodiffusion analysis with the use of antisera to TBG, 25K, 80/27K, HSA and IgG demonstrated that the proteins share no common antigenic determinants. It was concluded that the novel 25K and 80/27K proteins represent endogenous components of the human blood thyroid hormone-binding protein system rather than fragments or aggregates of the known T4-binding proteins. PMID- 2111183 TI - Neuroendocrine aspects of primary endogenous depression. X: Serum growth hormone measures in patients and matched control subjects. AB - To determine the extent of dysregulation of growth hormone (GH) secretion in endogenous depression, we measured nocturnal serum GH concentrations and GH responses to thyrotropin-releasing hormone (TRH, gonadotropin-releasing hormone (LHRH), and dexamethasone administration in 40 Research Diagnostic Criteria primary, definite endogenous depressives and 40 individually matched normal control subjects. Compared with their controls, the patients showed no difference in basal nocturnal GH concentrations or in GH responses to TRH or LHRH. The GH measures were not significantly related to the other endocrine measures reported previously, including dexamethasone suppression test status. None of the diagnostic schemes for endogenous/melancholic depression which we studied was significantly related to the GH measures in the patients. Of the other subject and symptom variables, the mood depression factor of the Hamilton depression scale and the performance difficulty factor of the Beck depression inventory were moderately negatively correlated with the nocturnal GH measures. These findings suggest that, in contrast to the previously reported hypothalamopituitary-adrenal cortical and thyroid axis abnormalities in our patients, GH secretion was relatively normal. Patients with more severe depressed mood and greater difficulty accomplishing tasks did have moderately lower nocturnal GH values. PMID- 2111184 TI - Development of 1-cell embryos from different strains of mice in CZB medium. AB - One-cell embryos from several different strains of mice have been cultured to the blastocyst stage in CZB medium. CZB medium can be used to culture CF1 x B6SJLF1/J 1-cell embryos to the blastocyst stage provided glucose is introduced into the medium on Day 3 of culture. The amount of glucose required for embryo development was titrated using a concentration range of 5.5 to 49.5 mM. With the exception of the highest concentration, all glucose levels tested supported 65-85% development to the morula and blastocyst stages. Variations of CZB medium were tested for their ability to support the development of 1-cell embryos from 4 strains of mice. For embryos from CF1 and DBA/2J (both x B6SJLF1/J) mice, which exhibit a "2 cell block" to development in vitro, CZB medium containing glutamine with the addition of glucose on Day 3 supported optimum development from the 1-cell stage to morula and blastocysts (79% and 87%). For embryos from B6D2F1/J and CD1 female mice (both x B6SJLF1/J males), which do not exhibit a "2-cell block" to in vitro development, optimum development to morula and blastocyst stages (95% and 50%) was in CZB medium containing both glutamine and glucose from the start of culture. PMID- 2111185 TI - Arachidonic acid inhibits luteinizing hormone-stimulated progesterone production in hen granulosa cells. AB - Arachidonic acid has been proposed to function as a hormone-induced second messenger in a variety of mammalian endocrine tissues. The present studies were conducted to evaluate whether arachidonic acid, either added exogenously or released endogenously following treatment with physiologic (phospholipase A2) or pharmacologic (melittin) agents, influences basal and/or luteinizing hormone (LH) induced cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone production in granulosa cells from domestic hens. Phospholipase A2 (PLA2) and melittin treatments failed to alter basal concentrations of progesterone, whereas arachidonic acid had a slight stimulatory effect (only at the 50-microM dose) on progesterone levels, and no effect on cAMP. By contrast, arachidonic acid, PLA2, and melittin each inhibited LH-promoted progesterone production in a dose dependent fashion. The inhibitory effects of arachidonic acid on the progesterone response were determined to occur both prior and subsequent to cAMP formation since cAMP levels in arachidonic acid-treated cells were attenuated after treatment with 10 ng LH or 100 microM forskolin (at 10- to 100-microM doses of arachidonic acid), and progesterone production was decreased in the presence of 1 mM 8-bromo-cAMP (with 50 and 100 microM arachidonic acid). The post-cAMP mechanism of action is characterized by the inability of cells to convert 25 hydroxy-cholesterol, but not pregnenolone, to progesterone. The effects of arachidonic acid are probably direct, since pharmacologic inhibitors of the lipoxygenase (nordihydroguaiaretic acid) and cyclooxygenase (indomethacin) pathways of arachidonic acid metabolism failed to alter the suppression of PMID- 2111186 TI - Alterations in gonadotropin secretion and ovarian function in prepubertal gilts by elevated environmental temperature. AB - The effect of chronic exposure to elevated environmental temperature on gonadotropin secretion and ovarian function was studied in prepubertal gilts. Gilts were maintained under control (15.6 degrees C) or elevated temperature (33.3 degrees C) conditions from 150 to 180 days of age. Endocrine and ovarian responses to bilateral (BLO), unilateral (ULO), and sham ovariectomy were evaluated between 175 and 180 days of age. During the 96-h sampling period after BLO, plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were suppressed in heat-stressed females. Similarly, elevated temperatures abolished the transient rise in FSH and subsequent follicular growth normally associated with ULO. In contrast, environmental treatment had no effect on the secretion of FSH and LH after sham ovariectomy, yet the number of small follicles was lower in gilts exposed to elevated temperatures than in females maintained under control conditions. These results indicate that a chronic exposure to elevated environmental temperature during pubertal development diminished the ability of the hypothalamo-hypophyseal axis to secrete FSH and LH, which had physiological consequences on follicular growth. When provided an appropriate stimulus (ULO), an acute period of FSH secretion and subsequent development of follicles failed to occur in females exposed to elevated temperatures. Consequently, we propose that delayed puberty in gilts during periods of elevated environmental temperatures is due, in part, to a diminished capacity for gonadotropin secretion. PMID- 2111187 TI - Onset of compensatory hypertrophy of interstitial tissue and Leydig cells in rats hemicastrated around the time of puberty. AB - When rats were unilaterally castrated at 20, 30, and 40 days of age, only those rats hemicastrated at 40 days showed compensatory hypertrophy of the interstitial tissue and Leydig cells when killed 30 days after hemicastration. At the time of death, volume densities of interstitial tissue, Leydig cells, and vascular components were greater in 70-day-old hemicastrated rats than in intact rats of the same age. The total number of Leydig cells per testis in hemicastrated and intact rats was always the same at any age. Estimated Leydig cell volume in 70 day-old rats was twice that in intact rats. By contrast, the testes of 50- and 60 day-old rats at the time of death displayed essentially the same morphological features, regardless of whether animals were hemicastrated. The concentration of plasma testosterone was higher in 50-day-old controls than in hemicastrated rats. Seventy-day-old hemicastrated rats showed higher levels of plasma testosterone than controls. The level of plasma dihydrotestosterone in 60- and 70-day-old hemicastrated rats exceeded that in the controls. A significant increase in follicle-stimulating hormone was noted in 50- and 70-day-old hemicastrated rats compared to normal rats, while levels of luteinizing hormone were basically the same. The increase in Leydig cell volume, interstitial tissue volume, vascular component volume, and plasma testosterone level caused by hemicastration at 40 days of age differed from that at 20 and 30 days of age. PMID- 2111188 TI - Androgen selectively stimulates follicle-stimulating hormone-beta mRNA levels after gonadotropin-releasing hormone antagonist administration. AB - Gonadal steroids act both at the hypothalamus and pituitary to regulate gonadotropin subunit gene expression. To investigate positive feedback effects of sex steroids on gonadotropin subunit mRNA levels in vivo, independent of effects on gonadotropin-releasing hormone (GnRH), the following studies were performed. Male and female rats, 7 days following castration, received the potent Nal/Glu GnRH antagonist (GnRHA) (500 micrograms/kg/day) for 14 days to block endogenous GnRH activity. Subgroups of animals received either estradiol benzoate (E) (10 micrograms/100 g BW/day) or testosterone propionate (T) (500 micrograms/100 g BW/day) for the last 7 days to assess the effects of reintroduction of gonadal steroids during blockade of endogenous GnRH action. Intact rats and castrated animals that received vehicle served as controls. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were determined on trunk blood, and gonadotropin subunit mRNAs were determined by blot hybridization using radiolabeled probes specific for the rat FSH beta, alpha, and LH beta subunit and mouse beta-actin genes. Autoradiographic bands were quantitated by laser densitometry and subunit mRNA levels were compared to those in intact pituitaries. In these studies, GnRHA administration inhibited the post-castration rises in all three gonadotropin mRNAs, as well as in serum FSH and LH levels. GnRHA + E or GnRHA + T resulted in similar or further suppression of alpha and LH beta mRNA levels compared to GnRHA alone. In contrast, in both sexes, GnRHA + T stimulated FSH beta mRNAs and serum FSH levels toward those of gonadectomized controls. Thus, during GnRHA inhibition of endogenous GnRH activity, androgen uniquely stimulates FSH beta mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111189 TI - Analysis and stereoselective metabolism after separate oral doses of tocainide enantiomers to healthy volunteers. AB - The potential of stereoselective metabolism of tocainide was studied in six healthy volunteers after separate oral administration of the pure enantiomers in solution. A method was developed to convert the N-carbamoylglucuronide of tocainide in plasma and urine by base treatment to a hydantoin derivative which after extraction and silation was analysed by selected ion monitoring using a deuterated internal standard. Analytical problems concerning side-reactions during derivatization of the conjugate are discussed. The peak plasma levels of the enantiomers, observed at less than or equal to 2 h after dosing, were similar but plasma clearances and terminal half-lives were different after oral administration of (R)-tocainide (195.5 +/- 20.1 ml min-1 and 9.7 +/- 0.8 h) and (S)-tocainide (110.2 +/- 10.5 ml min-1 and 14.5 +/- 1.7 h). Over 0-96 h the averaged urinary recovery of (R)-tocainide was 36 per cent and of (S)-tocainide 50 per cent. Stereoselective metabolism was a likely mechanism for the observed differences as the urinary recovery of the conjugate formed from (R)-tocainide differed substantially from that of (S)-tocainide (45 vs 1.2 per cent of given dose). Plasma t1/2 of the (R)- and (S)-conjugate were 9.9 and 18.7 h, respectively, indicating formation rate limited kinetics of the metabolite. The renal clearances of the conjugates were not significantly different (131 vs 97 ml min-1). PMID- 2111190 TI - Comparison of linoleate, palmitate and acetate metabolism in rat ventral prostate. AB - Rat ventral prostate incorporated (1-14C)acetate, (1-14C)palmitate and (1 14C)linoleate into different phospholipids in a time-dependent process. The rate of incorporation into total phospholipids was higher with linoleate (10.0 nmol/g) than with either palmitate (5.8 nmol/g) or acetate (4.7 nmol/g). Predominant labelling with all the radioactive substrates assayed was found in choline glycerophospholipids (PC). The radioactive profiles for linoleate in the other ventral prostate phospholipids differed from those obtained with palmitate and acetate. Specifically linoleate was incorporated into inositol glycerophospholipids plus lysoethanolamine glycerophospholipids (PI + LPE) and not into sphingomyelin (SM), while palmitate and acetate incorporated into SM but not into PI + LPE. Acetate showed the highest oxidation to CO2 whereas no differences were observed in the radioactivity incorporated into CO2 from a saturated (palmitate) or an essential unsaturated fatty acid (linoleate). These studies also show zinc-dependence by the acetate to CO2 oxidation. PMID- 2111191 TI - Effects of mitogenic agents upon glucocorticoid action in human tonsillar T lymphocytes. AB - The treatment of human tonsillar T-lymphocytes with 4-phorbol 12-myristate 13 acetate (PMA), resulted in about two fold increase in glucocorticoid receptor (GR) number, without any significant change in the receptor affinity. This increase disappeared in the presence of cycloheximide. Alone, PMA and calcium ionophore A23187 did not affect, but together stimulated, like phytohaemagglutinin (PHA), leucine and, in particular, thymidine incorporation. PMA enhanced slightly the stimulatory effect of PHA. Alone, these agents failed to alter the suppressive effect of dexamethasone on thymidine and leucine incorporation; however, PMA-A23187 and PMA-PHA combinations appeared to antagonize the suppression by dexamethasone. PMID- 2111192 TI - GTP gamma S-induced calcium transients and exocytosis in human neutrophils. AB - Exocytosis and intracellular free calcium ([Ca2+]in) were simultaneously recorded in single human neutrophils using patch-clamp capacitance measurements and the fura-2 fluorescence ratio method. Intracellular application of guanosine-5'-O(3 thiotriphosphate) (GTP gamma S) stimulates both exocytosis and a calcium transient. The calcium transient starts to develop after a lag phase of approximately 40 s and normally appears to trigger the onset of exocytosis indicated by the beginning of the capacitance increase. After this delay [Ca2+]in increases from approximately 150 nM to approximately 600 nM with a sigmoidal time course. The peak concentration is reached within approximately 30 s but the main increase occurs during approximately 3 s. [Ca2+]in subsequently decays within 1-2 min to a level which is close to the resting value. This calcium transient is due to calcium release from inositoltrisphosphate-sensitive intracellular stores. Exocytosis also occurs if the calcium transient is abolished by intracellular EGTA but the lag phase is markedly prolonged. The GTP gamma S-induced calcium transient is very similar to that observed after stimulation with N-formyl methionyl-leucyl-phenylalanine. The interplay between guanine nucleotides, [Ca2+]in and exocytosis in neutrophils closely resembles previous results obtained in mast cells suggesting a similar regulation of exocytosis in both cell types. PMID- 2111193 TI - Determining the degree of malignancy of individual cases of mammary carcinoma on the basis of clinical, morphological and biochemical parameters. AB - The histological and histochemical findings and the clinical course of 160 cases of breast cancer were compared with the biochemical values of the content and pattern of glycosaminoglycans (GAG) in the tumour tissue. For this purpose the cases were divided into 4 groups of increasing malignancy of the tumours, based on the morphological data and the clinical course after radical mastectomy (4-9 years follow-up). Samples of tumour tissue were examined biochemically analytically for their total content of glycosaminoglycans and for their mg/g values of hyaluronic acid (H), chondroitin-4- and chondroitin-6-sulphates (CA + CC), dermatan sulphate (CB), heparan sulphate (HpS) and component (K). The statistical processing by means of the method of "discriminant analysis" of the corresponding GAG values in relation to the degree of malignancy displayed by the tumours yielded the following results: 1) the glycosaminoglycan patterns of the mammary carcinoma have characteristic features in common for the large majority of cases; 2) an exception of about 5% of the cases developed carcinomata with a very high (up to 100%) content of component. These cases generally have a more favourable clinical course (group 1); 3) the higher the ratio of hyaluronic acid to chondroitin sulphates the better the prognosis (groups 1 and 2, respectively). A ratio of hyaluronic acid to chondroitin sulphates under 0.5 indicates a poor prognosis (group 3 and 4, respectively); 4) high values of heparan sulphate and small ratios of hyaluronic acid to heparan sulphate also signal an unfavourable prognosis (groups 3 or 4). We consider that the above results are a means of defining the degree of malignancy of the breast tumours. PMID- 2111194 TI - Clinical studies on cell-mediated immunity in patients with urinary bladder carcinoma: blastogenic response, interleukin-2 production and interferon-gamma production of lymphocytes. AB - Patients with advanced malignant neoplasms have a variety of abnormal lymphocyte functions. We examined the PHA blastogenic response, interleukin-2 (IL-2) production and interferon-gamma (IFN-gamma) production of lymphocytes in 39 bladder cancer patients and 20 control subjects. Correlation between these parameters was also studied. IL-2 production was measured by 3H-thymidine labelled CTLL-2 assay, and IFN-gamma production was measured by immunoradiometric assay using 2 mouse monoclonal antibodies. As a result, in high stage bladder cancer patients, the PHA blastogenic response, IL-2 production and IFN-gamma production were impaired. However, these parameters were not significantly different between low stage bladder cancer patients and control subjects. There was a significant correlation between the PHA blastogenic response and IL-2 production but no significant correlation between the PHA blastogenic response and IFN-gamma production. PMID- 2111195 TI - Nitrogen requirements in severely injured patients. AB - The study was designed to evaluate nitrogen needs in severely injured patients during the first week after trauma. Thirty-nine patients aged from 18 to 65 years with a burn or fractures of more than two long bones were studied. Energy requirements were given parenterally as fat and glucose in isocaloric amounts. The patients were randomized into five groups receiving different amounts of nitrogen from zero to 0.3 g kg body-weight-1 24 h-1. Daily and cumulative nitrogen balance, urinary 3-methylhistidine excretion and nitrogen retention were calculated on days 2-8 after trauma. With no nitrogen, the mean(s.e.m.) daily nitrogen balance after the trauma was -13.8(0.5) gN. The balance improved markedly in groups with a nitrogen intake of up to 0.2 g kg body-weight-1 (P less than 0.001) compared with the no-nitrogen group. The 3-methylhistidine excretion increased because of the trauma in all groups with no statistically significant difference between the groups. Nitrogen retention decreased with increase in nitrogen supply and with time after injury. It is suggested that a nitrogen supply of 0.20 kg bodyweight-1 24 h-1 is optimal for severely injured patients during the first week after trauma. PMID- 2111196 TI - Costs and effectiveness of interventions in child maltreatment. AB - There has been increasing awareness of the need to prevent child maltreatment at a time of limited public funds. As a result, cost-effectiveness has become important in the planning of health care and social services. Evaluations of child maltreatment interventions that have been analyzed for their cost effectiveness are reviewed. There has been relatively little work in this area and much of it has serious methodological flaws. Nevertheless, research suggests that home health visitors, lay group counseling, and family and group therapy are promising interventions. Medical foster care has been shown to substantially reduce costs, but its effectiveness has not been determined. Current knowledge on the effectiveness of interventions in child maltreatment is limited, and this needs to be addressed in order to answer the question of cost-effectiveness. Recommendations are made for future research in the field. PMID- 2111197 TI - [Cell fusion in Leishmania (Kinetoplastida, Trypanosomatidae)]. AB - Cell fusion in Leishmania infantum and L. tropica was recorded by means of a camera and a video system. Promastigotes were obtained from cultures in both cases. Fusion began with attachment of the posterior extremities of two ovoid flagellates. Complete fusion, with disappearance of adjacent cell membranes took about five minutes. In parallel, the flagella appear larger and shorter. These observations support the hypothesis of genetic exchanges suggested by analysis of DNA and enzymatic proteins. PMID- 2111198 TI - [Implication of glucose 6 phosphate isomerase (EC 5.3.1.9) activity in blocking segmentation of the mouse ovum at the 2 cell stage in vitro]. AB - The mouse embryo, when grown in media containing glucose, synthesizes and accumulates glycogen. In certain strains, glucose could be responsible for the 2 cell block; it can be replaced for a short time by glutamine, but with an increase in embryo degeneration. We have tested the hypothesis according to which the problems of glycogen accumulation and the developmental arrest could be due to a metabolic lock involving glucose 6 phosphate isomerase (EC 5.3.1.9). Fructose is located immediately downstream from this metabolic lock. We have exactly replaced the glucose in Whittingham M16 culture medium by fructose: Medium F.M. With this culture medium, Swiss one cell embryos, which normally block in M16 medium (greater than 90%), do not block any longer at the 2 cell stage (11.6%). They can be cultured for 4 days with high rates of blastocyst formation (53.6%). Embryo degeneration (23.6%) is lower than that observed in CZB (31%), and not different from our control degeneration in vivo. Moreover fructose seems to be adequate all through the culture period as there is no need for further addition of metabolites, to obtain blastocysts, as observed for CZB. This demonstrates that a lock at the Glucose phosphate isomerase level is responsible for glycogen accumulation and the 2 cell block in the mouse embryo in vitro. PMID- 2111199 TI - [Partial purification of galactocerebroside sulfotransferase in the rat brain]. AB - We describe a method of partial purification of rat brain 3'-phosphoadenosine-5' phosphosulfate galactocerebroside sulfotransferase (EC 2.8.2.11, CST). The first steps consist of a Triton X-100 extraction of the enzyme from delipidated microsomes and the fractionation of this extract by precipitation with ammonium sulfate, followed by successive chromatography on hydrophobic gel (phenyl sepharose), heparin, gel filtration (Trisacryl GF2000), hydroxy-apatite and cation exchange resin (SP trisacryl). The denaturation of the enzyme and its instability account for the low enrichment achieved in terms of specific activity, but an evident simplification of the electrophoretic pattern was obtained. PMID- 2111200 TI - [Atmospheric pollution of animal origin: the urticating hairs of the processionary caterpillar (Thaumetopoea pityocampa Schiff.) (Insects, Lepidoptera)]. AB - Urticating hairs of pine processionary caterpillars are detectable in air using techniques designed for airborne microorganisms and pollen's research. As with pollens, abondance of hairs is correlated with distance of production zone and with local meterological conditions. Collected in Bordeaux, urticating hairs will be considered for allergists as pollens and other allergic particles. PMID- 2111201 TI - [A general solution to the linkage of anonymous medical data]. AB - The necessity for confidentiality entails that most medical data on files do not allow for a precise identification of patients. A statistical pattern has been defined to assess the average difference between the real (unknown) number of patients in the file and the approximate number derived by linkage from indirect available data (date of birth, sex,...). An example is here given, which allows for the epidemiological use of anonymous data concerning hospitalized patients at the Assistance Publique-Hopitaux de Paris. This method is of general application for all files of anonymous data. PMID- 2111203 TI - Mineralization of [14C]hexadecane and [14C]phenanthrene in crude oil: specificity among bacterial isolates. AB - Bacteria isolated from freshwater, marine, and estuarine samples were tested for the ability to produce 14CO2 from n-[1-14C]hexadecane or [9-14C]phenanthrene added to Prudhoe Bay crude oil. Of 138 isolates tested, 54 (39%) mineralized the model aliphatic compound hexadecane and 6 (4%) mineralized the model aromatic compound phenanthrene. None mineralized both compounds. There was no apparent correlation between degradative ability and genus or source. Additional hydrocarbon-degrading bacteria from diverse sources were tested and found to mineralize either hexadecane or phenanthrene. Of 61 hexadecane- and 21 phenanthrene-mineralizing bacteria tested, none mineralized both model compounds. Selected isolates and commercially available cultures were tested for mineralization of specific 14C-labelled mono-, di-, and tri-cyclic aromatics. An apparent hierarchy of degradation was observed: strains mineralizing the mono- and di-cyclic aromatics toluene and naphthalene did not mineralize biphenyl or the tricyclic aromatics anthracene and phenanthrene, whereas those strains that mineralized the tricyclic aromatics also mineralized the smaller substrates. Similarly, not all n-alkane-mineralizing isolates tested mineralized the isoprenoid pristane. A combined culture consisting of one aliphatic- and one aromatic-degrading isolate was tested for mineralization of the model compounds and for degradation of other crude oil components by gas chromatography. No synergism or antagonism was observed compared with degradation by the individual isolates. PMID- 2111202 TI - Specific inhibition of iturin biosynthesis by cerulenin. AB - Cerulenin, an inhibitor of fatty acid synthesis, inhibits the biosynthesis of iturin by Bacillus subtilis. With a cerulenin concentration of 2 micrograms/mL, 50% inhibition was achieved. At this concentration, cerulenin does not affect growth or total protein synthesis but does inhibit the incorporation of sodium [14C]acetate, [14C]myristic acid, and [14C]asparagine into iturin. Since cerulenin is known to block the condensation of malonyl-CoA subunits in the formation of fatty acids, the inhibition of iturin and beta-amino acid syntheses by cerulenin is discussed in relation with lipid synthesis. PMID- 2111204 TI - Valproic acid and panic disorder. AB - Valproic acid (VA), an anticonvulsant which increases GABAergic transmission was given to patients suffering from recurrent panic attacks. Ten consecutive outpatients were included in this study. After a seven day placebo washout period, patients were given a dose of 500 mg/day, which was gradually increased to a maximum of 2250 mg/day. A significant improvement was found in the symptomatology of patients as measured on the Clinical Global Impression Scale for panic severity (p less than 0.001), the Hamilton Psychiatric Rating Scale for Anxiety (p less than 0.001) and the panic factor of the SCL-90 (p less than 0.05). These findings support the hypothesis that VA is useful in the treatment of panic disorders. Further research should be carried out to assess its efficacy and safety. PMID- 2111205 TI - Solid, infiltrating variety of papillary cystic neoplasm of the pancreas. AB - Four tumors with histologic, histochemical, and ultrastructural characteristics of papillary cystic neoplasm of the pancreas but lacking the capsule commonly observed in papillary cystic neoplasm and infiltrating interiorly into the pancreatic parenchyma were seen in two men and two women who were 39 to 51 years old. These tumors contrasted with typical encapsulated papillary cystic neoplasms that show extrapancreatic growth and that are detected as a palpable abdominal mass in young women. These four tumors, although unpalpable, were all detected by nodular images of calcification in abdominal plain radiography. The tumors had a mean diameter of 3.1 cm (range, 1.7 to 4.5 cm), were confined within the pancreatic parenchyma, and showed central fibrosis accompanied by dystrophic changes such as calcification and ossification. A small necrotic cyst contiguous to the fibrous focus also was observed in the tumor in three patients. Tumor cells similar to those of a papillary cystic neoplasm had infiltrated among the pancreatic parenchyma in solid and pseudopapillary patterns, and pleomorphic atypism was observed in some parts of the tumor in three patients. These tumors were tentatively designated solid, infiltrating variety of papillary cystic neoplasms to differentiate them from ordinary encapsulated papillary cystic neoplasms. Although no signs of recurrence have been noticed after surgical treatment in these patients, the infiltrating growth pattern and the presence of pleomorphic atypism suggest higher malignancy than the ordinary papillary cystic neoplasm. The contrasting growth pattern and possible malignancy may warrant establishment of these tumors as a papillary cystic neoplasm subclass. PMID- 2111206 TI - Multiple myeloma presenting as space-occupying lesions of the liver. AB - Initial myeloma presentation as discrete liver nodules is unusual. A 59-year-old man who presented with hepatomegaly and multiple space-occupying lesions in the liver and who was found to have a lambda light chain multiple myeloma with hepatic plasmacytomas is described and a review of liver involvement in multiple myeloma is presented. PMID- 2111207 TI - Intimacy and cognitively impaired elders. PMID- 2111208 TI - Persistently increased expression of a 3-methylcholanthrene-inducible phenol uridine diphosphate-glucuronosyltransferase in rat hepatocyte nodules and hepatocellular carcinomas. AB - Increased UDP-glucuronosyltransferase in rat hepatocyte nodules and hepatocellular carcinomas produced by feeding 2-acetylaminofluorene or N nitrosomorpholine was studied using isozyme-selective substrates, antibodies, and DNA probes. UDP-glucuronosyltransferase (UDP-GT) activities toward 4 methylumbelliferone, 1-naphthol, and benzo[a]pyrene-3,6-quinol were reversibly increased by short term feeding of 2-acetylaminofluorene but were persistently increased in hepatocyte nodules and differentiated hepatocellular carcinomas. Immunoblot analysis revealed that short term feeding of 2-acetylaminofluorene increased a Mr 55,000 polypeptide corresponding to the previously characterized UDP-GTI or phenol UDP-GT. However, in some hepatocyte nodules and hepatocellular carcinomas either the Mr 55,000 or a new Mr 53,000 polypeptide was preferentially increased, suggesting heterogeneous UDP-GT forms in liver nodules and carcinomas. Northern blot hybridization with a synthetic DNA probe to phenol UDP-GT demonstrated increased levels of mRNA in liver nodules. The results suggest persistently increased expression of at least two phenol UDP-GT enzyme forms in hepatocyte nodules, which may contribute to the toxin-resistance phenotype frequently observed at cancer prestages. PMID- 2111209 TI - Isolation and characterization of a rat liver epithelial cell line resistant to the antiproliferative effects of transforming growth factor beta (type 1). AB - Rat liver epithelial cells resistant to the growth-inhibitory effects of transforming growth factor beta 1 (TGF-beta 1) were isolated after 3 h exposure to 1.5 micrograms/ml of N-methyl-N'-nitro-N-nitrosoguanidine followed by continuous treatment with 1 ng/ml TGF-beta 1 for 6 weeks. In comparison to the parental or N-methyl-N'-nitro-N-nitrosoguanidine-exposed rat liver epithelial cells (concentration causing 50% inhibition of the rate of DNA synthesis, 0.25 ng/ml), these cells were 10-fold more resistant to the antiproliferative effects of TGF-beta 1 and exhibited resistance to growth inhibition by a highly purified liver-derived growth inhibitor, recombinant human tumor necrosis factor, and transforming growth factor beta 2. Single cell cloning of these resistant cells led to the isolation of a nontransformed clonal cell population (clone 11) which maintained stable resistance in the absence of TGF-beta 1 treatment. Binding of 125I-labeled TGF-beta 1 to rat liver epithelial cells and clone 11 cells was similar. Clone 11 cells exhibited a 5-10-fold resistance to the cytotoxins Adriamycin and vinblastine as assessed by a clonogenic assay. This drug resistance was accompanied by an increase in the steady state levels of the mRNAs for multidrug resistance gene (MDR-1), glutathione S-transferase-P, TGF-beta 1, and c-myc genes. The data presented here suggest an association between resistance to the growth-inhibitory effects of TGF-beta 1- and MDR-1-mediated multidrug resistance. PMID- 2111210 TI - The journal of CardioVascular and Interventional Radiology. PMID- 2111211 TI - Percutaneous biopsy of thoracic lesions in children. AB - Over the last 6 years, 15 percutaneous thoracic biopsies have been performed in 15 children. The peripheral nature of most of the lesions allowed ultrasound guidance in ten and needles larger than 21 gauge in ten. No pneumothorax developed. Of the 15, 12 biopsies were sufficient for final diagnosis; 3 required surgical biopsy for more definitive tissue typing. PMID- 2111212 TI - The biocompatibility of compressed collagen foam plugs. AB - The tissue reaction to reexpanded, purified bovine collagen sponge placed percutaneously into the lung, pleural space, liver, kidney, and muscle was studied in dogs and rabbits. In addition, the biocompatibility and radiopacity of tantalum-treated collagen foam plugs was examined. No adverse effects were found. We believe that collagen plugs may be of use in occluding needle tracts from biopsy sites to prevent complications such as bleeding or pneumothoraces. PMID- 2111213 TI - Magnetic resonance imaging evaluation of spontaneous portosystemic collaterals. AB - Three patients, two of whom had histories of episodic hepatic encephalopathy, were shown by magnetic resonance imaging (MRI) to have occult spontaneous portosystemic shunts. The multiplanar imaging capabilities of MRI provided an optimal, noninvasive method of visualization of collateral anatomy in each case. PMID- 2111214 TI - Late Greenfield filter vena cava perforation causing a small bowel obstruction: case report. AB - This report describes a symptomatic case of vena caval perforation caused by a vena cava filter. Functional small bowel obstruction due to vascular compromise was caused by a prong of the filter. PMID- 2111215 TI - Computed tomographic diagnosis of left superior vena cava and absence of the azygos vein: case report. AB - The radiologic findings on plain chest films and contrast-enhanced computed tomography (CCT) of the thorax in a case of isolated persistence of the left superior vena cava associated with absence of the right azygos vein are described. Chest x-rays allowed a presumptive diagnosis of the vascular anomaly. Confirmation of this anomaly was achieved by CT. PMID- 2111216 TI - Detecting and assessing severity of coronary artery disease in humans. AB - Quantitation of stenosis severity has become an essential part of cardiac diagnosis and therapy, not only in research but also in clinical practice. Since our introduction of the concept 15 years ago, arterial coronary flow reserve for assessing effects of coronary narrowing has evolved into two independent but complementary measurements: coronary flow reserve and stenosis flow reserve. Coronary artery flow reserve and/or myocardial perfusion reserve takes into account not only stenosis geometry but also collateral function and physiologic conditions of perfusion pressure, vasomotor tone, coronary venous pressure, and myocardial vascular bed size. Coronary artery flow reserve is measured invasively by flowmeter or by Doppler catheter. Its noninvasive equivalent is myocardial perfusion reserve, assessed by myocardial perfusion imaging with positron emission tomography before and after intravenous dipyridamole with hand grip stress. Both have been experimentally and clinically validated for identifying and/or quantifying severity of coronary artery disease. By either invasive or noninvasive methods, coronary artery or myocardial perfusion reserve may be subcategorized as either absolute flow or perfusion reserve (max flow/resting flow) and/or relative flow or perfusion reserve (max flow through stenotic artery/max flow through normal artery). Absolute flow reserve depends not only on stenosis severity but also on unrelated physiologic parameters such as aortic pressure and the vasodilatory state of the distal coronary vascular bed; in contrast, relative flow reserve is independent of these physiologic variables and reflects stenosis severity alone. Stenosis flow reserve is invasively determined by automated, quantitative coronary arteriography accounting for all stenosis dimensions and is independent of ambient physiologic conditions such as pressure, vasomotor tone, or other variables affecting the distal coronary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111218 TI - Hepatic arterial embolization utilizing a coaxial catheter system: technical note. AB - A coaxial catheter system using the Tracker Hi-Flow catheter was utilized to perform 38 hepatic arterial embolizations in 20 patients. These embolizations would not have been feasible if the ability to superselectively catheterize the segmental arteries and negotiate tortuous vessels had not been available. This is a valuable technique for use in superselective hepatic arterial embolizations. PMID- 2111217 TI - Embolization of a thoracic aortic aneurysm; the straddling coil technique: technical note. AB - Occlusion of a patent postligated aortic aneurysm was performed percutaneously with modified use of giant steel coils in a 50-year-old man. Steel coils were placed across the short, narrowed segment of the aorta. Successful thrombosis of entire aortic aneurysm was accomplished. No complications occurred. PMID- 2111219 TI - Transnasogastric drainage of a perforated duodenal ulcer: technical note. AB - Perforated peptic ulcers are usually managed surgically after failure of more conservative medical treatment of ulcer disease. This case illustrates transnasogastric placement of a drainage catheter through a perforated ulcer, which was successful as definitive therapy. PMID- 2111220 TI - Early experiences with the stable isotope method in children. AB - A new technique to estimate water uptake by the gastrointestinal tract was tested in infants undergoing elective surgery. Patients were randomly allocated to receive either sterile water or a glucose-electrolyte solution labeled with the stable isotope H2O18. After absorption, the isotopic O18 comes to rapid equilibrium with plasma bicarbonate and subsequently appears in the breath as C18O2. Breath and blood samples were collected at five-minute intervals after administration of the test solution. Mass spectrometric analysis enabled detection of isotopic O18 enrichment at parts per million levels in blood and in breath CO2. Enrichment of blood and breath C18O2 above baseline levels is detectable within five minutes of administration of the labeled test solution and rises to a plateau between 30 and 90 minutes. It is hypothesized that the rate of increase of enrichment is proportional to the unidirectional flux of water from lumen to gut. PMID- 2111221 TI - Effect of pH on acid production from sorbitol in washed cell suspensions of oral bacteria. AB - The acid production from sorbitol and glucose was studied under anaerobic conditions in resting cell suspensions of bacteria from the predominant sorbitol fermenting human dental plaque flora, belonging to the genera Streptococcus, Lactobacillus and Actinomyces. The acid production activity of the bacterial cells was followed by titration with alkali, at environmental pH 7.0, 6.0 and 5.0 after addition of carbohydrate solution. The metabolic end products formed in the suspensions were analyzed thereafter by isotachophoretic and enzymatic methods. The results showed that sorbitol was fermented at a slower rate than glucose. Lowering the environmental pH decreased the acid production activity from the two carbohydrates. Compared with glucose, the catabolism of sorbitol was affected to greater extent by the pH conditions. The total amount of acids formed from sorbitol was considerably less than from glucose. Lactic acid, which was the major end product in glucose-challenged suspensions, was produced only in low concentrations from sorbitol by all strains tested. The ratio strong (formic + lactic)/weak acids was moreover lower for sorbitol than for glucose. The present results further illustrate some of the mechanisms behind the low cariogenic potential of this sugar substitute. PMID- 2111222 TI - Mutans streptococci in interproximal plaque from amalgam and glass ionomer restorations. AB - Interproximal plaque samples were collected from newly made class II conventional conservative amalgam (Dispersalloy) and glass ionomer (Ketac Silver) tunnel restorations in 20 adolescents. The percentage viable count of mutans streptococci in samples from glass ionomer restorations (mean 3.1%, median 0.7%) was significantly lower (p less than 0.05) than in samples from amalgam restorations (mean 5.7%, median 3.1%). This suggests that plaque formed on such restorations might have a lower potential to induce recurrent caries than plaque formed on amalgam restorations. PMID- 2111223 TI - [The prolactin and TSH response to stimulation in patients with hypophyseal tumors]. AB - The authors examined the prolactin (PRL) and thyrotropin (TSH) response to stimulation with chloropromazine and thyreoliberin in 10 patients with pituitary tumours. They observed a hypothalamic response instead of the expected pituitary response. These findings may be of importance for the understanding of the aetiopathogenesis of pituitary tumours. As we are able to influence nowadays some expansive pituitary processes by conservative treatment, these findings may in the near future be important in clinical practice. PMID- 2111224 TI - [Fabry's disease with isolated disease of the cardiac muscle, manifesting as hypertrophic cardiomyopathy]. AB - A case is presented of Fabry's disease manifesting in an adult (aged 64) as hypertrophic nonobstructive cardiomyopathy caused by massive ceramidtrihexoside storage confined exclusively to the cardiocytes. There was no storage detectable in capillaries or in any other structure of the organs examined (liver, pancreas, brain, aorta, pulmonary artery, coronary arteries, heart valves). The clinical picture was dominated by heart failure slowly progressing during the last fifteen years of the patient's life terminated by pulmonary thromboembolism. There were no clinical signs of ocular, renal or skin affection. Since no unfixed tissues were available for enzyme analysis diagnosis had to be done using formaldehyde fixed tissues. The isolated stored lipid was characterized by TLC and by proton magnetic resonance analysis as globotriaosyl ceramide (Gal alpha 1-4 Gal beta 1-4 Glc beta 1-1' Cer) and was proved to be cleaved by control cell homogenates but left intact by those prepared from Fabry mutant cells (leukocytes, cultured fibroblasts). alpha galactosidase activity in each of his four daughters was in heterozygous range (peripheral leukocytes were used for analysis). The existing variants of cardiological syndromes in Fabry's disease are reviewed together with problems of diagnosis of atypical cases. PMID- 2111225 TI - [Respiratory changes in rabbits during metabolic acidemia]. AB - The authors investigated the hyperventilation reaction during acute metabolic acidaemia in anaesthetized rabbits with preserved vagi and after vagotomy. They assessed the respiratory pattern, partial CO2 pressure and pH of arterial blood [PaCO2, pHa]. The value of the minute ventilation [VE] did not differ in animals with intact vagi and those after vagotomy. In rabbits after vagotomy the VE was more effective, as apparent from pHa values. The protraction of the period of expiration [Te] by extension of the expiratory break in vagotomized animals suggests a facilitating action of the vagal pulmonary feedback on the expiration- inspiration activity [inspirium on-switch system]. PMID- 2111226 TI - Sertoli and Leydig cell numbers and gonadotropin receptors in rat testis from birth to puberty. AB - In testes of rats from 2 to 60 days of age, we examined the number of Sertoli cells (SC) and Leydig cells (LC) as well as the binding of radioiodinated gonadotropins to frozen sections and homogenates. The number of SC per testis increased only during the first 2 postnatal weeks, whereas that of LC was stable up to days 7-10 and increased thereafter. The uptake of 125I-labelled human follicle-stimulating hormone (125I-FSH) to frozen sections was confined to sex cords or seminiferous tubules, while that of 125I-labelled human choriogonadotropin (125I-hCG) matched the distribution of LC in the interstitium. High affinity receptors for FSH and hCG were found in homogenates at all stages studied. The number of FSH receptors per testis increased steadily, whereas that of hCG receptors was low until days 7-10 and rose afterwards. Thus, SC in rat testis appear to proliferate in the presence of fetal LC during the first 2 postnatal weeks and to differentiate concomitantly with the emergence of the adult LC generation after day 10. The complement of FSH receptors in SC remains constant as they proliferate and increases after day 21 as they differentiate. The hCG receptor number is relatively fixed in each LC generation, being higher in adult compared to fetal LC. PMID- 2111227 TI - Functional expression of microsomal and mitochondrial cytochrome P-450 (d and SCC) in COS-7 cells from cloned cDNA. AB - Using full length cDNA introduced into COS-7 cells, two species of P-450 with entirely different physiological functions have been expressed in enzymatically active form. One is P-450d, which is known to reside in the microsomes of rat hepatocytes where it acts as a drug-metabolizing enzyme; the other is P-450(SCC), which catalyzes the conversion of cholesterol to pregnenolone in the rate limiting reaction of steroidogenesis in mitochondria of adrenal cortex cells. Northern blot and immunoblot analyses revealed that the mRNA and protein of these P-450 species were efficiently produced in COS-7 cells. The protein contents amounted to nearly 0.1% of the total cell protein as estimated from immunoblotting and low temperature CO difference spectra. The subcellular localization of the products indicated that they were correctly sorted to the microsomes and mitochondria, respectively. We have succeeded in eliciting most of the activity of the expressed microsomal P-450d by reconstruction with NADPH cytochrome P-450 reductase, while the optimal conditions for the mitochondrial enzyme in the COS cells remain to be studied. These results show the applicability of the COS-7 expression system to investigations of the functions of members of the P-450 superfamily whose cDNA has been newly isolated. PMID- 2111228 TI - Cloning and expression of a hybrid Streptomyces clavuligerus cefE gene in Penicillium chrysogenum. AB - A hybrid cefE gene was constructed by juxtaposing promoter sequences from the Penicillium chrysogenum pcbC gene to the open reading frame of the Streptomyces clavuligerus cefE gene. In S. clavuligerus the cefE gene codes for the enzyme penicillin N expandase [also known as deacetoxycephalosporin C synthetase (DAOCS)]. To insert the hybrid cefE gene into P. chrysogenum the vector pPS65 was constructed; pPS65 contains the hybrid cefE gene and the Aspergillus nidulans amdS gene. The amdS gene encodes acetamidase and provides for dominant selection in P. chrysogenum. Protoplasts of P. chrysogenum were transformed with pPS65 and selected for the ability to grow on acetamide medium. Extracts of cells cultivated in penicillin production medium were analyzed for penicillin N expandase activity. Penicillin N expandase activity was detected in approximately one-third of the transformants tested. Transformants WG9-69C-01 and WG9-61L-03 had the highest specific activities of penicillin N expandase: 4.3% and 10.3%, respectively, relative to the amount of penicillin N expandase in S. clavuligerus. Untransformed P. chrysogenum exhibited no penicillin N expandase activity. Analysis of the penicillin V titer revealed that WG9-61L-03 produced titers equal to that of the recipient strain while the amount of penicillin V produced in WG9-69C-01 was reduced by five fold. PMID- 2111230 TI - A genetic analysis of glucoamylase activity in the diastatic yeast Saccharomyces cerevisiae NCYC 625. AB - The wild diastatic yeast Saccharomyces cerevisiae NCYC 625 has been shown to be homozygous for the glucoamylase-specifying gene STA2. spoII-1-mapping has positioned STA2 on chromosome II. Expression of STA2 is suppressed in some but not all diploids capable of sporulation, and is also inhibited by unlinked nuclear suppressor genes (SGL) found in some S. cerevisiae tester strains. EMS induced glucoamylase-negative mutants often contain STA2-suppressor mutations. Depending on the allelic status of GEP1, a nuclear gene which also appears able to antagonise SGL-mediated suppression, STA2 expression can be blocked in petite mutants. PMID- 2111229 TI - The psbA-gene from a red alga resembles those from cyanobacteria and cyanelles. AB - Plastid DNA (ptDNA) from the unicellular red alga Cyanidium caldarium was isolated. A 5.8 kb Eco RI, fragment containing the entire psbA-gene was cloned and the nucleotide sequence of the psbA-gene determined. At the carboxyl terminus the encoded protein (D1) contains the seven amino acid-insertion which was found to be typical of the cyanobacteria and the cyanelles of Cyanophora paradoxa. However, the overall sequence homology does not support a direct relationship between the plastids of Cyanidium, cyanelles and the cyanobacteria. As in other photosynthetic organisms the psbA-gene is transcribed as a monocistronic mRNA. The ribosomal RNA operon was located 4 kb upstream of the psbA-gene. PMID- 2111231 TI - Effect of low mole fraction of trehalose dicorynomycolate from Corynebacterium diphtheriae on water permeability and electrical capacitance of lipid bilayer membranes. AB - The effect of incorporation of different proportions of trehalose dicorynomycolates (TDC) into lecithin bilayer membranes was studied. It was found that TDC, induces a 14% decrease of water osmotic permeability (42.6 +/- 3.9 to 36.8 +/- 2.7 microns/s) at 1.6 mole%, suggesting that this substance leads to an increase of the degree of packing of the constituent lipid molecules. A condensing effect of TDC was also apparent from membrane electrical capacitance (Cm) measurement. By incorporating TDC into bilayer membranes, the value of Cm experienced a decrease of 29% at 1.6% mole fraction. This finding was taken to reflect an increase in membrane thickness, known in many examples, to be related to the condensing effect. PMID- 2111232 TI - Changes in arterial oxygen saturation in cigarette smokers following general anaesthesia. AB - The effect of cigarette smoking on postoperative arterial oxygen saturation was evaluated in 45 adult patients using pulse oximetry. Patients were divided into a smoking group (n = 20) and a non-smoking group (n = 25) based on current smoking habits up until the time of surgery. The two groups were similar with respect to sex, ASA physical status, surgical procedure, duration of anaesthesia, narcotic and anaesthetic use and recovery characteristics. The non-smoking group was, however, significantly (P less than 0.05) older than the smoking group. Postoperative oxygen saturation (SaO2) decreased (P less than 0.001) during transport of both groups of patients from the Operating Room to the Recovery Room; a decrease which was significantly greater in the smoking group. The severity of hypoxaemia was also significantly greater in the smoking group than in the non-smoking group. This study suggests that cigarette smoking contributes to postoperative arterial oxygen desaturation following general anaesthesia and that supplemental oxygen should be administered to these patients during postoperative transport. PMID- 2111233 TI - Lipid peroxidation and covalent binding in the early functional impairment of liver Golgi apparatus by carbon tetrachloride. AB - The onset of the lipoprotein secretory block provoked by CCl4 in the whole animal was monitored after purification of liver Golgi membranes. Both lipid transit through the apparatus and hexosylation of the lipoprotein are markedly inhibited 5-15 min after poisoning. Pre-treating the animal with alpha-tocopherol, shown to prevent lipid peroxidation without modifying the covalent binding due to CCl4 metabolites, affords little protection against lipid accumulation in the Golgi, but total preservation of galactosyl transferase activity. While haloalkylation therefore appears to be the major mechanism of damage in the early phases of CCl4 induced derangement of lipid secretion, lipid peroxidation is probably more involved later; this is indicated by the marked, though never complete, protection against fatty liver afforded at 24 h after CCl4 poisoning by supplementation of the membrane with alpha-tocopherol. PMID- 2111234 TI - Evidence of the receptor nature of the binding sites induced in Tetrahymena by insulin treatment. A quantitative cytofluorimetric technique for the study of binding kinetics. AB - Tetrahymena pyriformis GL cells pretreated (imprinted) and not pretreated with insulin showed dissimilar quantitative relations of FITC-insulin binding. Displacement of FITC-insulin by unlabelled insulin was considerably less in the control than in the imprinted series. The curve for saturation of the binding sites with FITC-insulin resembled a true saturation curve. The imprinted cells bound considerably more hormone in a shorter time than the control cells at identical levels of exposure. The dissociation of bound hormone from the imprinted cells increased over the control at 23 degrees C, and to a still greater degree at 4 degrees C. The effect of the pH of the medium on the dissociation of bound FITC-insulin also differed between the imprinted and not imprinted cells. Thus the proposed cytofluorimetric assay of binding kinetics demonstrated the actual conditions of receptor activity, and indicated that the induced insulin binding sites of Tetrahymena behaved similarly to 'classical' receptors. PMID- 2111235 TI - Insulin-like growth factor I stimulates proliferation, migration, and plasminogen activator release by human retinal pigment epithelial cells. AB - The migration of retinal pigment epithelial (RPE) cells from their normal anatomic position to a new position in the vitreous cavity is a critical feature of proliferative vitreous retinopathy. To determine if insulin-like growth factor I (IGF I), which is present in the vitreous fluid of diabetics, stimulates RPE cells, we examined the effects of IGF I on the proliferation, chemotaxis, and release of plasminogen activator by these cells. At the concentrations of IGF I tested, significant proliferation of RPE cells is seen. Significant chemotaxis of the RPE cells also is seen at all the concentrations of IGF I tested. The mean number of migrating cells per high-powered field in control studies was 43 +/- 13 (x +/- SEM), and for IGF I at 2.5 ng and 50 ng/ml the mean numbers of migrating cells were 96 +/- 17 and 483 +/- 62, respectively (P less than 0.001 for each comparison). The IGF I response was noted to be dose-dependent. The chemotactic response noted at 50 ng/ml of IGF I was greater than the positive chemotactic control of 10% fetal calf serum. Addition of alpha IR-3, an IGF I receptor antibody, eliminated the IGF I chemotactic response. The effect of IGF I on the secretion of plasminogen activators was assessed using an immunological assay for tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). Media conditioned by RPE cells have measureable levels of PAI and t-PA antigen. IGF I supplementation resulted in an increase of t-PA secretion and PAI secretion over basal levels. These studies support a role for IGF I in modulating RPE cell function. PMID- 2111236 TI - Glycosaminoglycans of human trabecular meshwork in perfusion organ culture. AB - The synthetic profile of glycosaminoglycans (GAGs) of human trabecular meshwork in perfusion organ culture was studied in a series of 34 human eyes. The anterior segments of these eyes were cultured for periods of two to 28 days and received medium containing 3H-glucosamine and 35S-sulfate during the final 48 hours of culture. The meshwork was then dissected and the GAGs isolated and subjected to sequential enzyme digestion. Active labelling of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparan sulfate was found in all time periods. Eyes cultured seven and 14 days had similar incorporation profiles to "fresh" eyes (cultured 48 hours to allow for labelling). Eyes cultured 21 days showed an increase in dermatan sulfate labelling and a slight decrease in keratan sulfate labelling when compared with "fresh" eyes. Light microscopic autoradiography confirmed the trabecular meshwork incorporation of the radiolabelled precursors at all time periods. Thus, the trabecular meshwork remains metabolically active and GAG synthetic profiles remain reasonably similar to fresh eyes for up to three weeks in a perfusion organ culture system. This system may serve as a model for future studies of human trabecular meshwork GAGs. PMID- 2111237 TI - Expression of 87A, 87C and 93D heat shock puffs in trisomic (2L and 3L) strains of Drosophila melanogaster: evidence for a functional relation between 93D and 87C. AB - Chromosomal RNA synthesis of the three heat shock puffs 87A, 87C and 93D examined in trisomic 3L (T3L) and trisomic 2L (T2L) strains of Drosophila melanogaster and compared with that of Oregon R+ and compound stocks of the 3rd [C(3L)VGI ru st; F(3R)VDI es/F(3R)VDI es] and 2nd [C(2L)SHI+; F(2R) bw] chromosomes. The activity at two different temperatures (22 degrees and 37 degrees C) was monitored by [3H]uridine autoradiography. The results that while in the control T3L and T2L nuclei (22 degrees C), the 93D puff shows a higher level of transcriptional activity than in the Oregon R+ or compound stocks used as controls, in T3L and T2L nuclei from heat-shocked sets (37 degrees C), 93D does not show further induction compared with heat-shocked controls, and the 87C puff is 2.8 times more active than the 87A puff. These results suggest that there may be a direct functional and/or regulatory relationship between the activity of 93D and certain sequence specific activity of 87C, and that an optimum level of activity delimits the activity of the heat shock puff 93D in D. melanogaster. PMID- 2111238 TI - Immunohistochemical localization of glycated protein in diabetic rat kidney. AB - The localization of glycated protein in the kidney of diabetic rats was examined immunohistochemically with antiserum against glucitol-lysine. In diabetic rats the brush border and basement membrane of the proximal convoluted tubules were strongly immunoreactive with the antiserum but in control rats, only the brush border was weakly reactive. The immunoreactive tubules were more abundant in diabetic rats. No immunoreaction was found in any other structures in the kidney. Glycation of the proximal convoluted tubules may be an alteration in diabetic nephropathy. PMID- 2111239 TI - Insulin and sulphonylurea in the therapy of type 2 diabetes. AB - The role of insulin in the therapy of NIDDM is still under discussion. To clarify the problem we performed a randomized double-blind placebo controlled crossover study of insulin treatment for 4 weeks in diabetic patients (n = 18, age 52-74 years) who were unsatisfactorily controlled by oral antidiabetic agents. The patients continued to use these agents during the study. Special attention was given to informing the patients about the trial and, in particular, about self monitoring the blood glucose by the use of a reflectance meter. Insulin treatment produced the following significant changes: decreases in blood glucose (at 7.00, 10.00, 16.00), mean daily blood glucose, HbA1, urinary glucose and low density lipoprotein (LDL) cholesterol and increased postglucose immunoreactive insulin (IRI) levels. Significant changes were also observed during the placebo periods: decreases in HbA1 urinary glucose and LDL cholesterol (but not in blood glucose). Therapy with insulin increased the body weight, whereas the placebo insulin had the opposite effect. The finding emphasizes the importance of using not only a run-in period but also a placebo design when the metabolic effects of antidiabetes therapy are to be evaluated. The study indicates that insulin therapy for patients with type 2 diabetes can be initiated at home. PMID- 2111240 TI - Functional properties of proislet isografts in diabetic mice. AB - Fetal proislets (islet precursors) were transplanted to isogeneic diabetic CBA/H mice for analysis of their development and function post-transplant. Immunohistochemically, proislets contained scattered populations of insulin-, glucagon- and somatostatin-producing cells; following isotransplantation proislets developed into mature islet tissue with normal endocrine cell composition. Proislet isografts also developed normal endocrine function after transplantation to diabetic mice. Isografts of eight and four donor-equivalents of proislets reversed streptozotocin-induced diabetes by 30 +/- 7 and 74 +/- 26 days, respectively. Following stimulation with intragastric glucose (50 mg) mice carrying established isografts of four donor-equivalents of proislets exhibited normal blood glucose responses; those grafted with eight donor-equivalents of proislets showed decreased blood glucose levels. The beta cell mass of proislets continued to grow and differentiate post-transplant; established proislet grafts contained greater than 100-fold the total insulin content of the corresponding number of fetal pancreases from which the proislets were derived. The mean insulin content of eight and four donor-equivalent proislet grafts was 231% and 156%, respectively, that of the mean content of adult mouse pancreas. The data show that glucose homeostasis can be restored in diabetic mice following isotransplantation of fetal proislets and that the quantity of tissue transplanted is a critical parameter in achieving optimal control. PMID- 2111241 TI - Spatial and temporal distribution of vinculin and talin in migrating avian neural crest cells and their derivatives. AB - Neural crest cells express different adhesion modes at each phase of their development starting with their separation from the neural tube, followed by migration along definite pathways throughout the embryo, and finally to settlement and differentiation in elected embryonic regions. In order to determine possible changes in the cytoskeleton organization and function during these processes, we have studied the in situ distribution of two major cytoskeleton-associated elements involved in the membrane anchorage of actin microfilaments, i.e. vinculin and talin, during the ontogeny of the neural crest and its derivatives in the avian embryo. Prior to emigration, neural crest cells exhibited both vinculin and talin at levels similar to the neighbouring neural epithelial cells, and this expression apparently did not change as cells became endowed with migratory properties. However, vinculin became selectively enhanced in neural crest cells as they further migrated towards their final destination. This increase in vinculin amount was particularly striking in vagal and truncal neural crest cells entering cellular environments, such as the sclerotome and the gut mesenchyme. Talin was also expressed by neural crest cells but, in contrast to vinculin, staining was not conspicuous compared to neighbouring mesenchymal cells. High levels of vinculin persisted throughout embryogenesis in almost all neural derivatives of the neural crest, including the autonomous and sensory ganglia and Schwann cells along the peripheral nerves. In contrast, the non neural derivatives of the neural crest rapidly lost their prominent vinculin staining after migration. The pattern of talin in the progeny of the neural crest was complex and varied with the cell types: for example, some cranial sensory ganglia expressed high amounts of the molecule whereas autonomic ganglia were nearly devoid of it. Our results suggest that (i) vinculin and talin may follow independent regulatory patterns within the same cell population, (ii) the level of expression of vinculin and talin in neural crest cells may be consistent with the rapid, constant modulations of their adhesive properties, and (iii) the expression patterns of the two molecules may also be correlated with the genesis of the peripheral nervous system. PMID- 2111242 TI - Altered host response and special infections in the elderly. AB - Infection remains one of the most common causes for Emergency Department evaluation and hospital admission in the elderly. Unfortunately, aged individuals may not manifest the typical symptoms and signs as their younger counterparts. The emergency physician must recognize that the elderly individual may exhibit a less vigorous physiologic response to infectious states, which can delay or make diagnosis difficult. This article attempts to explain the apparent dysfunctions in the elderly that places this important population at greater risk for certain infections. PMID- 2111243 TI - Valproic acid-induced carbamazepine-10,11-epoxide toxicity in children and adolescents. AB - The study of 14 children and adolescents shows that the addition of carbamazepine (CBZ) to a basic valproic acid (VPA) therapy can result in unexpectedly high concentrations of carbamazepine-10,11-epoxide (CE) in the serum (up to 13 micrograms/ml). These concentrations were associated with marked side effects, especially vomiting and tiredness. The concentrations of CBZ were within the therapeutic range. Very high CE concentrations can largely be avoided at the commencement of the CBZ treatment if the CBZ dose is slowly increased. But high CE concentrations (4-8 micrograms/ml) associated with side effects can also be reached in later stages during the build up of CBZ treatment and under steady state conditions. The determination of the CE concentration is important when VPA and CBZ are administered together, especially when side effects occur. PMID- 2111244 TI - The effect of the benzodiazepine antagonist, flumazenil, on psychometric performance in acute ethanol intoxication in man. AB - The effect on cognitive and psychomotor performance of the benzodiazepine (BZD) antagonist, flumazenil, in antagonising the central effect, of ethanol in man has been investigated. Eight healthy adult male volunteers, aged 23 to 32 years, participated in the study. Following a loading infusion, stable blood ethanol levels with a mean value of 1.6 g x l-1 were produced by a maintenance infusion. When stable blood levels of ethanol were reached, 5.0 mg flumazenil/placebo was administered intravenously, and after 15 and 75 min a test battery evaluating psychomotor and cognitive functions was applied. The test battery was sensitive to the test model, but no significant improvement in the test scores could be demonstrated following the administration of flumazenil. It is concluded that flumazenil has no influence on psychomotor functions in acute ethanol intoxication. PMID- 2111245 TI - Altered flecainide disposition in healthy volunteers taking quinine. AB - The pharmacokinetics of flecainide and its two sequential metabolites, both free and conjugated, its pharmacodynamics, and the influence of simultaneously administered quinine, have been studied in 10 healthy subjects. The study comprised two, 48-h open phases at an interval of 1 week. Flecainide acetate 150 mg was given as a 30-min i.v. infusion and quinine sulphate orally 500 mg x 3 over 24 h. Quinine administration did not change the apparent volume of distribution or the renal clearance of flecainide, but it significantly reduced its systemic clearance (9.1 vs 7.6 ml.kg-1.min-1), thus increasing the elimination half-life (9.6 vs 11.5 h). The amount of flecainide transformed to its first, meta-O-dealkylated metabolite (MODF) fell with no change in the renal excretion of the latter, either in its free or conjugated forms. This finding, in association with a fall in amount of the second, meta-O-dealkylated lactam metabolite (MODLF) recovered in its conjugated forms in the urine, suggests that quinine inhibits both the first and the second steps of the sequential metabolism of flecainide. When the subjects received quinine in addition to flecainide, the PR interval in the ECG was slightly more prolonged than with flecainide alone. Due to the study design, an effect of quinine per se and the consequence of increased serum flecainide levels could not be distinguished. PMID- 2111246 TI - Pharmacokinetics of a valpromide isomer, valnoctamide, in healthy subjects. AB - The pharmacokinetics of a single 400 mg oral dose of valnoctamide (VCD) has been investigated in seven healthy, adult, male volunteers. VCD was not biotransformed rapidly to its corresponding acid valnoctic acid (VCA), unlike its isomer valpromide (VPD). It had a mean residence time of 13.2 h and a terminal half-life of 9.3 h. Throughout the study, only low plasma levels of VCA could be detected. Thus, unlike VPD, which is a pro-drug of the corresponding acid, (valproic acid, VPA). VCD appears to act as a drug in its own right, and it does not undergo similar hydrolysis. The pharmacokinetic difference may account for the different pharmacological activities of the two isomers. PMID- 2111248 TI - Enhancement of A23187-induced release of enteric vasoactive intestinal polypeptide by phorbol 12,13-dibutyrate. AB - The effect of phorbol 12,13-dibutyrate on calcium ionophore (A23187)-induced release of vasoactive intestinal polypeptide from enteric nerves was examined. A23187 caused release of vasoactive intestinal polypeptide dose dependently and phorbol 12,13-dibutyrate (100 nM) markedly shifted the dose-response curve of A23187 to the left. The significance of these findings will be discussed in relation to the mechanism of release of vasoactive intestinal polypeptide from enteric nerves. PMID- 2111247 TI - Effects of Ca2+ entry blockers on CaCl2-, KCl- and noradrenaline-induced contractions of goat cerebral arteries. AB - The effects of three Ca2+ entry blockers, nicardipine, nimodipine and verapamil, on CaCl2-, KCl- and noradrenaline-induced contractions were examined in isolated goat middle cerebral artery. The relationship between the effects of Ca2+ entry blockers and the extracellular Ca2+ dependence of the contractions was also examined. In 'nominally' Ca2(+)-free medium, addition of CaCl2 induced concentration-dependent contractions of previously depolarized arteries. Withdrawal of Ca2+ from the extracellular medium caused strong inhibition of the KCl- and noradrenaline-induced arterial contractions. Addition of EGTA to the Ca2(+)-free medium almost abolished the noradrenaline-response but did not increase the inhibition of the KCl-induced contractions. The Ca2+ entry blockers induced concentration-dependent relaxation of the precontracted arteries (100 mM KC1) with the following order of potency: nimodipine greater than nicardipine greater than verapamil. The CaCl2-, KCl- and noradrenaline-induced contractions were depressed in a concentration-related manner by nicardipine, nimodipine and verapamil. Dihydropyridines showed a greater inhibitory effect than verapamil. These results show that Ca2+ entry blockers are able to inhibit the contractile responses of goat cerebral arteries to KCl and noradrenaline, an effect which may be explained by the strong dependence of both responses on extracellular Ca2+. PMID- 2111250 TI - [The epidemiology and prevention of anthrax]. PMID- 2111249 TI - PEEP-masks in patients with severe obstructive pulmonary disease: a negative report. AB - Positive pressure during expiration by face masks applied by the patient has gained wide acceptance in the treatment of chronic bronchitis, but the efficacy is still unproven. The effect of 6 months of treatment with PEEP-masks (positive end-expiratory pressure) was therefore studied in 47 patients with severe irreversible obstructive pulmonary disease (forced expiratory volume in one second (FEV1) about 1 l), and mucus hypersecretion. Patients were double-blindly randomized to at least 45 min daily treatment with PEEP-masks with either 10 or 0 cm water pressure. After 6 months of treatment, no statistical difference was found between the two groups in change of median values (month 6 - month 0) of FEV1, forced vital capacity (FVC), arterial oxygen tension (PaO2), amount of sputum or dyspnoea. Median values of arterial carbon dioxide tension (PaCO2) decreased significantly (0.03 kPa) in the placebo group. Cough intensity and dyspnoea during walking on staircases improved significantly in the placebo group. No difference among groups was found in number of days bedridden, hospitalized, number of exacerbations or antibiotic consumption. We conclude, that the use of PEEP-masks in these patients is without clinical documentation and cannot be recommended. PMID- 2111251 TI - Comparison of the analgesic and anti-inflammatory effects of diclofenac potassium versus piroxicam versus placebo in ankle sprain patients. AB - In a double-blind between-patient study the efficacy of diclofenac potassium, a non-steroidal anti-inflammatory drug, was assessed in 93 patients with mild to severe sprained ankles; patients with more severe sports injuries were excluded. Patients were randomly allocated to receive 50 mg diclofenac potassium three times daily, 20 mg/day piroxicam or placebo for 7 days. Diclofenac potassium was more effective than piroxicam or placebo in reducing pain at rest and on walking, but did not significantly reduce the degree of swelling when measured volumetrically by water displacement. No serious side-effects were reported. It is concluded that diclofenac potassium is useful in the treatment of moderately inflammatory processes with the advantage that it had a rapid onset of action with good overall tolerability. PMID- 2111252 TI - Randomized double-blind, placebo-controlled clinical trial of a selective 5 lipoxygenase inhibitor (AA-861) for the prevention of seasonal allergic rhinitis. AB - In a randomized, double-blind, parallel group trial conducted in eight European centres, the 5-lipoxygenase inhibitor AA-861 was administered orally, starting 2 weeks before the pollen season and continuing for 8 weeks; after the start of the season escape medication was permitted if necessary. Patients were enrolled who had a previous history of pollen allergy, confirmed by skin prick tests and/or relevant allergen-specific immunoglobulin E to pollen. Daily symptoms scores were recorded on diary cards and assessments were made by the investigator during the study period. Better global improvement ratings were achieved using AA-861, as assessed both by the investigators and the patients. The total nasal symptoms scores and activities of daily living were also improved compared to placebo. No significant adverse reactions were encountered. PMID- 2111253 TI - Inhibin in immature rat Sertoli cell conditioned medium: a 32 kDa alpha beta-B dimer. AB - Conditioned medium of cultured Sertoli cells from 21-day-old rats was used as starting material for the isolation of inhibin. Inhibin activity was monitored by the dose dependent suppression of the follicle-stimulating hormone release of cultured rat pituitary cells. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis of the highly purified inhibin preparation revealed a 32 kDa protein after silver staining, which could be separated in subunits of 18 kDa and 12 kDa after reduction. Western blot analysis with an antibody recognizing the 22 N-terminal amino acids of the alpha-subunit of 32 kDa bovine inhibin confirmed the presence of a 32 kDa inhibin molecule under non-reducing conditions, whereas an 18 kDa alpha-subunit was found after reduction. An antibody recognizing the beta-A subunit of inhibin did not yield a signal after Western blotting. N-terminal amino acid sequence analysis of two highly purified preparations of inhibin obtained using different methods yielded the sequence predicted for a 32 kDa alpha beta-B dimer on basis of cDNA nucleotide sequence. This result is in agreement with the large excess of beta-B over beta-A mRNA in the rat testis. PMID- 2111254 TI - A high concentration of dopamine preferentially permitted release of newly synthesized prolactin. AB - We used continuous labelling ([3H]leucine) of cultured adenohypophysial cells to investigate the relationship between the storage and release of newly synthesized and stored prolactin in response to dopamine (1 mumol/l) and thyrotropin releasing hormone (TRH) (0.1 mumol/l) challenge. Newly synthesized prolactin was identified by the tritium radiation activity incorporated in prolactin. A maximal dose of dopamine (1 mumol/l) could not completely block prolactin release from a primary culture of lactotrophs. During 3 h of continuous labelling under maximal dopaminergic inhibition, newly synthesized prolactin was released which was of a significantly higher specific activity than control groups. In contrast, TRH stimulation produced results consistent with previous observations of the release of predominantly old, stored hormone. However, the absolute amount of the newly synthesized prolactin was increased by the TRH administration, and the increased release of the newly synthesized prolactin could be accounted for by increased levels of synthesis. Our results are consistent with the concept of the existence of a regulated route and a dopamine-insensitive constitutive route of prolactin release which predominantly encompasses newly synthesized hormone. However, the possibility that cellular heterogeneity or that non-dopaminergic prolactin release inhibiting factor(s) (PIF) is responsible for this observed release cannot be ruled out. PMID- 2111255 TI - Mouse preproacrosin: cDNA sequence, primary structure and postmeiotic expression in spermatogenesis. AB - The primary structure of mouse preproacrosin was deduced by nucleotide sequencing of cDNA clones isolated from a mouse testis cDNA library. The largest cDNA, with 1373 bp, consists of a 11-bp 5'untranslated sequence, a 1254-bp open reading frame terminated by a TGA triplet and a 105-bp 3' untranslated end, including one potential polyadenylation signal. The NH2-terminus of the polypeptide contains a hydrophobic 15-amino acid signal peptide. This cleavable signal sequence is followed by 403 amino acids, representing the acrosin light and the heavy chain of 23 and 380 amino acid residues, respectively. The proteolytic active site segments His, Asp and Ser are part of the heavy chain, as well as a proline-rich COOH-terminus, which is not present in any other serine proteinase studied so far. Furthermore the postmeiotic expression of the preproacrosin gene during mouse spermatogenesis was studied. PMID- 2111256 TI - The in vivo erythrocyte micronucleus test: measurement at steady state increases assay efficiency and permits integration with toxicity studies. AB - The mouse erythrocyte micronucleus assay has been traditionally carried out using one or two exposures to the test agent, followed by sampling at two or three postexposure times to obtain a sample near the time of the transient peak of micronucleated polychromatic erythrocytes (PCEs). We have demonstrated that frequencies of micronucleated RNA-positive (PCEs) and RNA-negative erythrocytes in blood and bone marrow come to steady state during "continuous" exposure via diet or drinking water, or during repeated daily exposures to test agents by ip injection, gavage, or inhalation. Under these exposure conditions, frequencies of micronucleated cells in peripheral blood approached steady state within 2-3 days in RNA-positive erythrocytes and in 5-6 weeks in RNA-negative erythrocytes. With exposure durations of 6 days (monocrotaline or Crotalaria seeds in diet), 10 days (triethylenemelamine, mitomycin C, 7,12-dimethylbenzanthracene, or colchicine, ip daily), 90 days (triethylenemelamine or urethan in drinking water or 1,3 butadiene via inhalation), or 2 years (benezene by daily gavage), frequencies of micronucleated cells attained and remained at steady state for prolonged periods. At steady state, frequencies of micronucleated RNA-positive cells in bone marrow samples were similar to those in RNA-positive and RNA-negative cells in peripheral blood (e.g., triethylenemelamine in drinking water at 4 micrograms/ml resulted in frequencies of micronucleated RNA-negative erythrocytes in peripheral blood of 27/1000 after 45 days of exposure and 24/1000 after 90 days, with a frequency of 28/1000 in bone marrow RNA-positive erythrocytes after 90 days). The data suggest that the efficiency of the assay would be markedly improved by using a repeated dose schedule with a single sample taken at steady state, rather than scoring multiple samples at various times after a single dose. This approach allows the frequency of micronucleated cells to be measured in a sample of bone marrow or blood obtained at almost any stage of routine toxicity testing. PMID- 2111258 TI - Comparative study of the in vitro synthesis of prostaglandins and thromboxanes in plants belonging to Liliaceae family. AB - 1. Homogenates of garlic (Allium sativum), onions (Allium cepa) and Allium porum were in vitro incubated with [14C]arachidonic acid. 2. Separation of labelled prostaglandins and thromboxanes were accomplished by thin-layer chromatography (TLC) and the Rf values were compared with those of authentic standards. 3. The prostaglandins identified were 6-keto-PGF1 alpha, PGF2 alpha, TXB2, PGE2 and PGD2. 4. PGE2 and PGD2 were the major metabolites of arachidonic acid among all the members of the Liliaceae family studied. 5. Garlic was found to have the highest capacity to metabolize the [14C]arachidonic acid into prostaglandins and thromboxanes. 6. The synthesis of prostaglandins and thromboxanes, was inhibited by preincubation of homogenates with indomethacin or was completely destroyed by boiling the plant extract prior to incubation with arachidonic acid. This confirmed the presence of cyclooxygenase in these plants. PMID- 2111259 TI - The role of histidine residues in the alpha toxin of Clostridium perfringens. AB - The alpha-toxin (phospholipase C) of Clostridium perfringens has been reported to contain catalytically essential zinc ions. We report here that histidine residues are essential for the co-ordination of these ion(s). Incubation of alpha toxin with diethylpyrocarbonate, a histidine modifying reagent, did not result in the loss of phospholipase C activity unless the protein was first incubated with EDTA, suggesting that zinc ions normally protect the susceptible histidine residues. When the amino acid sequences of three phospholipase C's were aligned, essential zinc binding histidine residues in the non-toxic B. cereus phospholipase C were found in similar positions in the toxic C. perfringens enzyme and the weakly toxic C. bifermentans phospholipase C. PMID- 2111257 TI - Role of the Ah locus in suppression of cytotoxic T lymphocyte activity by halogenated aromatic hydrocarbons (PCBs and TCDD): structure-activity relationships and effects in C57Bl/6 mice congenic at the Ah locus. AB - Previous studies have shown that the generation of cytotoxic T lymphocytes (CTL) following allogeneic tumor challenge is suppressed in Ah-responsive C57Bl/6 mice treated with a single oral dose of the toxic, Ah receptor-binding 3,4,5,3',4',5' hexachlorobiphenyl (HxCB). The present studies have examined the specific role of the Ah receptor in this immunotoxic response by utilizing HxCB isomers of known, varied affinity for the Ah receptor as well as by comparing effects of high affinity Ah receptor ligands (3,4,5,3',4',5'-HxCB and 2,3,7,8-tetrachlorodibenzo p-dioxin [TCDD]) on the CTL response of mice that differ only at the Ah locus, that is, Ah-responsive (Ahbb) and Ah-nonresponsive (Ahdd) congenic C57Bl/6 mice. Correlative changes in thymic weight, serum corticosterone (CS) levels, and spleen cellularity were also measured. The potency of HxCB congeners (3,4,5,3',4',5'-; 2,3,4,5,3',4'-; 2,4,5,2',4',5'-) and 2,3,7,8-TCDD to suppress the CTL response, to reduce spleen cellularity, to cause thymic atrophy, and to elevate serum CS levels was directly correlated with the binding affinity of the congener for the Ah receptor. Furthermore, these parameters of immunotoxicity in Ahdd C57Bl/6 mice were significantly more resistant to alterations induced by either 3,4,5,3',4',5'-HxCB or 2,3,7,8-TCDD as compared to Ahbb C57Bl/6 mice. These results strongly support an Ah receptor-dependent immunotoxic mechanism in suppression of the CTL response following acute exposure to halogenated aromatic hydrocarbons. PMID- 2111260 TI - Surface Listeria monocytogenes carbohydrate-binding components revealed by agglutination with neoglycoproteins. AB - Carbohydrate-binding components were shown to be present at the surface of Listeria monocytogenes by means of a panel of neoglycoproteins using direct agglutination. These lectin-like components bind on neoglycoproteins bearing D glucosamine, L-fucosylamine, or para-amino-phenyl-alpha-D-mannopyrannoside residues. The interactions were inhibited by the carbohydrate moieties specific to the neoglycoproteins. The protein nature of the lectin-like components of L. monocytogenes was ascertained by the loss of carbohydrate-binding capacity following protease treatment. PMID- 2111261 TI - Do beta-lactam antibiotics permeabilize the outer membrane of gram-negative bacteria? An electrochemical investigation. AB - The effects of cefotaxime and EDTA on the reducing activity of Escherichia coli and Staphylococcus aureus cultures growing in the presence of lipoic acid (LA) were investigated by potential-time measurements. The potentiometric responses of E. coli cultures exposed to EDTA indicated enhanced transmembrane transport of LA as a consequence of the outer membrane permeabilization by the chelator, whereas EDTA exerted no effect on the reducing activity of S. aureus cultures. In the same way, cefotaxime stimulated the reducing activity of E. coli, but not that of S. aureus. These results suggest that cefotaxime, and, more generally, a great variety of beta-lactam antibiotics, are able to permeabilize the outer membrane of Gram-negative bacteria. PMID- 2111262 TI - The genetic analysis of distributive segregation in Drosophila melanogaster. II. Further genetic analysis of the nod locus. AB - In Drosophila melanogster females the segregation of nonexchange chromosomes is ensured by the distributive segregation system. The mutation noda specifically impairs distributive disjunction and induces nonexchange chromosomes to undergo nondisjunction, as well as both meiotic and mitotic chromosome loss. We report here the isolation of seven recessive X-linked mutations that are allelic to noda. As homozygotes, all of these mutations exhibit a phenotype that is similar to that exhibited by noda homozygotes. We have also used these mutations to demonstrate that nod mutations induce nonexchange chromosomes to nondisjoin at meiosis II. Our data demonstrate that the effects of noda on meiotic chromosome behavior are a general property of mutations at the nod locus. Several of these mutations exhibit identical phenotypes as homozygotes and as heterozygotes with a deficiency for the nod locus; these likely correspond to complete loss-of function or null alleles. None of these mutations causes lethality, decreases the frequency of exchange, or impairs the disjunction of exchange chromosomes in females. Thus, either the nod locus defines a function that is specific to distributive segregation or exchange can fully compensate for the absence of the nod+ function. PMID- 2111263 TI - The organization and expression of the light gene, a heterochromatic gene of Drosophila melanogaster. AB - The light (lt) gene is located in the centromeric heterochromatin of chromosome 2 of Drosophila melanogaster. This gene is necessary for normal levels of pigmentation in a number of adult and larval tissues and is required for viability. Hybrid dysgenic and X-ray induced mutations have been used to identify the gene and compare its organization to that of euchromatic genes. Molecular mapping of lt mutations and its major transcripts has shown that the lt gene is at least 17 kb. By injecting cosmid clones that include this region into lt mutant embryos, we have defined a 30-kb region that can transiently rescue the pigmentation defect in the Malpighian tubules. The major transcription unit of this gene is comprised of exons that are single copy. It is unusual in its organization in having a heterogeneous array of middle repetitive DNA sequences within its intronic and flanking regions. PMID- 2111264 TI - The effects of chromosome rearrangements on the expression of heterochromatic genes in chromosome 2L of Drosophila melanogaster. AB - The light (lt) gene of Drosophila melanogaster is located at the base of the left arm of chromosome 2, within or very near centromeric heterochromatin (2Lh). Chromosome rearrangements that move the lt+ gene from its normal proximal position and place the gene in distal euchromatin result in mosaic or variegated expression of the gene. The cytogenetic and genetic properties of 17 lt variegated rearrangements are described in this report. We show that five of the heterochromatic genes adjacent to lt are subject to inactivation by these rearrangements and that the euchromatic loci in proximal 2L are not detectably affected. The properties of the rearrangements suggest that proximity to heterochromatin is an important regulatory requirement for at least six 2Lh genes. We discuss how the properties of the position effects on heterochromatic genes relate to other proximity-dependent phenomena such as transvection. PMID- 2111265 TI - Interacting genes that affect microtubule function in Drosophila melanogaster: two classes of mutation revert the failure to complement between haync2 and mutations in tubulin genes. AB - The recessive male sterile mutation haync2 of Drosophila melanogaster fails to complement certain beta 2-tubulin and alpha-tubulin mutations, suggesting that the haywire product plays a role in microtubule function, perhaps as a structural component of microtubules. The genetic interaction appears to require the presence of the aberrant product encoded by haync2, which may act as a structural poison. Based on this observation, we have isolated ten new mutations that revert the failure to complement between haync2 and B2tn. The revertants tested behaved as intragenic mutations of hay in recombination tests, and fell into two phenotypic classes, suggesting two functional domains of the hay gene product. Some revertants were hemizygous viable and less severe than haync2 in their recessive phenotype. These mutations might revert the poison by restoring the aberrant product encoded by the haync2 allele to more wild-type function. Most of the revertants were recessive lethal mutations, indicating that the hay gene product is essential for viability. These more extreme mutations could revert the poison by destroying the ability of the aberrant haywirenc2 product to interact structurally with microtubules. Flies heterozygous for the original haync2 allele and an extreme revertant show defects in both the structure and the function of the male meiotic spindle. PMID- 2111267 TI - 'Wasting away' of the old old: can it--and should it--be treated? AB - Asthenia/cachexia, a syndrome which may manifest as a "wasting away," is growing in importance as the number of those ages 75 to 85 and over 85 increases. The syndrome has clearly identifiable laboratory abnormalities, a multitude of etiologic factors, and serious consequences. Accurate diagnosis of the causative agent is often difficult, since asthenia/cachexia is associated with aging, acute disease, and chronic disease. In addition, empiric treatment is often unpleasant and causes grief to families attempting to provide humane care for parents and grandparents at the end of life. The goal of the practitioner is to identify and intervene judiciously in the progressive deterioration of individuals who develop asthenia/cachexia and its complications. PMID- 2111266 TI - The apparent specificity of NotI (5'-GCGGCCGC-3') is enhanced by M.FnuDII or M.BepI methyltransferases (5'-mCGCG-3'): cutting bacterial chromosomes into a few large pieces. AB - The restriction endonuclease (ENase) NotI is blocked by methylation within its recognition sequence at 5'-GCGGCmCGC-3'. This sensitivity to methylation can be used to enhance the specificity of NotI in vivo and in vitro. Modification by M.FnuDII or M.BepI methyltransferases (MTase) (5'-mCGCG-3') will block NotI (5' GCGGCCGC-3') cleavage at overlapping MTase/ENase sites 5'-CGCGGCCGC-3' (equivalent to 5'-GCGGCCGCG-3'), and increase the apparent cleavage specificity of NotI about twofold. This 'cross-protection' procedure reduces the number of NotI fragments in the genomes of Escherichia coli and Bacillus subtilis, as resolved by pulsed field electrophoresis. Application of this method to large DNAs in vitro requires the preparation of highly purified DNA MTases. PMID- 2111268 TI - [Neonatal short bowel syndrome. Etiology, pathogenesis and treatment]. PMID- 2111269 TI - The effect of loading on tibiotalar alignment in cadaver ankles. AB - The tibiotalar movements which occur with axial loading, without applied moment forces were studied in cadaver ankles using a minimally constrained testing apparatus. Lateral translation of the talus measured up to 2 mm, which was associated with increased tibiotalar valgus angulation. Neither displacing the distal fibula laterally, nor sectioning the deltoid ligament, significantly influenced the talar shift. The tibiotalar motion which was observed after simple axial loading in a stable configuration (e.g., fibula and deltoid ligament intact) is of the same magnitude that is usually regarded as signifying an unstable ankle fracture. Consequently, this study suggests that the criteria for an unstable ankle fracture may need closer scrutiny. PMID- 2111270 TI - Inhibition of human and rabbit platelet activation by Ketotifen. AB - The effects of Ketotifen and disodium cromoglycate were investigated on human and rabbit platelet activation. Ketotifen inhibited dose-dependently human and rabbit platelet aggregation. The paf-acether pathway was the most markedly influenced by Ketotifen in human and rabbit platelets (IC50 = 38.8 +/- 7.7 microM and 7.2 +/- 4.5 microM respectively) as compared to adenosine diphosphate (IC50 greater than 100 microM and 79 +/- 19 microM) and to arachidonic acid (IC50 greater than 100 microM and 98 +/- 28 microM). Similar concentrations of Ketotifen inhibited the ATP release from human platelets induced by paf-acether. Disodium cromoglycate up to 5 x 10(-4) M did not inhibit platelet aggregation induced by paf-acether, adenosine diphosphate and arachidonic acid. PMID- 2111271 TI - How chronically administered valproate increases chlordiazepoxide transfer through the blood-brain barrier. AB - Sodium valproate (VPA) is a drug widely used in the treatment of epileptics often in association with benzodiazepines. Recent animal studies have shown that the addition of valproate increases diazepam levels in the cortex and the cerebellum (Hariton et al, 1985). The aim of our study was to determine the effect of VPA on the transfer of benzodiazepines through the blood-brain barrier. They were investigated using the intracarotid injection technique in rats as described by Oldendorf (1971). Our results show that the 14C-chlordiazepoxide brain extraction is significantly higher in rats on prolonged valproate treatment than in controls. With regard to plasma protein binding effects on chlordiazepoxide transport, our data indicate that a fraction of the protein-bound chlordiazepoxide could transfer from the intracapillary space to the brain tissue space because of enhanced drug dissociation from albumin in the brain microcirculation (Kd in vitro = 74.1 microM; Kd in vivo = 793.7 microM). Two distinct mechanisms can be deduced from this study: 1) chlordiazepoxide is displaced from HSA by valproate, 2) in addition, this fatty acid could increase drug permeation through the blood brain barrier (PS/F (chlordiazepoxide) = 0.60 in controls, PS/F (chlordiazepoxide) = 0.97 in treated rats). On the contrary, the washout of the benzodiazepine from the rat brain does not seem to be modified by the addition of valproate. PMID- 2111272 TI - Low activities of disaccharidases associated with inflamed duodenal bulb mucosa. AB - In order to establish whether an enzymatic method (a "functional" test) could be used instead of the histological picture as an indicator of damage to enterocytes of duodenal mucosa, biopsies were taken from 39 patients with upper gastrointestinal symptoms suggestive of peptic ulcer disease, but without active ulcers at endoscopy. Eleven patients with a normal appearance of the duodenal bulb mucosa and twenty-eight patients with various degrees of endoscopic inflammation ("bulbitis") were evaluated. The histological degree of duodenitis was assessed, and the activities of maltase, invertase, trehalase and lactase in the biopsy specimens were measured. Disaccharidase activities were inversely proportional to severity in both endoscopic and histological scoring of degree of inflammation. Low disaccharidase activities were also present in patients with endoscopic inflammation of the duodenal bulb, but without histological duodenitis. Focal and especially widespread gastric metaplasia was, in itself, significantly associated with low disaccharidase activities. The correlation between endoscopic and histologic scoring of inflammation of duodenal mucosa was not significant as assessed by kappa statistics. A previous history of peptic ulcer disease was significantly more common in patients with, than in those without, endoscopic inflammation of the duodenal bulb. PMID- 2111273 TI - HCFA chief won't budge on Medicare budget cuts. AB - Gail Wilensky, Ph.D., head of the Health Care Financing Administration, has time on her side. Four months into the job, Wilensky has received high marks from various segments of the health care field for her broad outlook and no-nonsense approach to numerous issues. Still, final judgment is being reserved until Wilensky is forced to address some tough issues. And in today's environment, there are plenty of tough issues ahead--the 1991 budget, for instance. PMID- 2111274 TI - The changing pattern of antibiotic resistance of Neisseria gonorrhoeae. PMID- 2111275 TI - Transfer of beta-lactamase plasmids by conjugation in Neisseria gonorrhoeae. AB - Conjugation experiments in vitro have been used in an attempt to explain certain epidemiological phenomena seen amongst penicillinase producing Neisseria gonorrhoeae (PPNG) isolated at St Mary's Hospital, London. These include changes in plasmid profiles, a lack of beta-lactamase encoding plasmids in PAOU-requiring strains and a difference in the serological classification of strains of PPNG and non-PPNG isolated from the same clinic. It was shown that acquisition of the conjugative plasmid by beta-lactamase producing transconjugants does vary, but is not related to the auxotype/serovar (A/S) class of, or type of beta-lactamase plasmid carried by the donor. It was not possible to transfer either the 3.2MDa or 4.4MDa plasmids to PAOU-requiring strains of N gonorrhoeae. The conjugation frequency from a single donor to different recipients was shown to be variable, but was not influenced by the serovar of the recipients. It was shown that the transfer and acceptance of beta-lactamase encoding plasmids is variable but it was not possible to identify the factors responsible. PMID- 2111276 TI - Antibiotic resistance, plasmid profile, auxotypes and serovars of Neisseria gonorrhoeae strains isolated in Sevilla (Spain). AB - The antibiotics resistance pattern, the plasmid profile, the auxotypes and serotypes of 116 Neisseria gonorrhoeae clinical isolates obtained in one year were examined. The incidence of penicillinase producing (PPNG) strains was 12% (14 strains). The most frequent plasmid pattern was the combination of 4.5, 2.6 and 24.5 MDa plasmids. The conjugative plasmid of 24.5 MDa showed a high prevalence (32% of the total strains), and almost all the PPNG strains harboured this plasmid. The strains with the 4.5 MDa plasmid belonged to the auxotypes Pro , Zero and Pro-Hyx-Ura-, whereas that with the 3.2 MDa plasmid was of auxotype Pro-Hyx-His-. The serotypes Aedih/Arst (WI serogroup) and Bak/Bropt, Back/Bropyt and Bak/Bropyt (WII/III serogroup) were predominant. PMID- 2111277 TI - Mapping of mouse carbonic anhydrase-3, Car-3: another locus in the homologous region of mouse chromosome 3 and human chromosome 8. AB - At least six separate genes determining tissue- and organelle-specific isoforms of carbonic anhydrase are known. We have determined the chromosome location of one of these genes, carbonic anhydrase-3 (Car-3), in the mouse and carried out a linkage analysis of Car-1, Car-2, and Car-3. Car-3 has been assigned to band 3A2 by in situ hybridization. We identified a PstI restriction fragment length polymorphism between Mus spretus and Mus mus domesticus and, by using an interspecific backcross, showed that Car-3 is 2.4 +/- 1.7% SE from both Car-1 and Car-2, calculating genetic distance as percentage recombination. No recombinants were found between Car-1 and Car-2 in 100 backcross offspring, and when these data are combined with earlier results, these two loci are estimated to be 1.2 cM from each other at the 95% confidence interval. The three homologous carbonic anhydrase loci in man had earlier been assigned to 8q22, and the finding of linkage of Car-3 to Car-1 and Car-2 in the mouse adds another locus to the conserved segments on mouse chromosome 3 and human chromosome 8. PMID- 2111278 TI - Pentose synthesis in glucose-grown cells of Lactobacillus casei. AB - The pathway of pentose synthesis in glucose-grown cells of Lactobacillus casei was ascertained. Glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were present in glucose-grown cells, while transaldolase and transketolase were present only in traces. This suggested that only the oxidative arm of this pathway was operative in glucose-grown cells. On the other hand, in ribose-grown cells, transaldolase was induced with a concomitant suppression of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. These results were confirmed by the detection of labelled CO2 produced by L. casei grown on [1-14C]glucose. The activities of the enzymes of the oxidative pentose phosphate pathway as also the rate of CO2 formation were higher in the exponential phase of growth as compared to the stationary phase, when the requirement of the cells for pentoses for the formation of DNA and RNA was higher. PMID- 2111279 TI - Effect of metal chelators on thermoluminescence peaks of spinach chloroplasts and photosystem II particles: probing the water oxidation cycle with 8 hydroxyquinoline. AB - Inhibition of photosystem II (PS II) activity by 8-hydroxyquinoline (8-HQ) has been investigated in case of spinach chloroplasts and isolated photosystem II particles using the thermoluminescence technique. In presence of 8-HQ, water to methylviologen (MV) photoreduction in isolated chloroplasts is inhibited while the reduction of dichlorophenol indophenol is inhibited in both chloroplasts as well as in photosystem II particles. The activity can be restored fully by addition of diphenylcarbazide (DPC), suggesting that the donor side of water oxidation complex is affected. The changes in the thermoluminescence peaks indicate that the charge recombination processes involving S2 or S3 states of the Kok's cycle are probably affected by 8-HQ treatment. PMID- 2111280 TI - Mucinophilic and chemotactic properties of Pseudomonas aeruginosa in relation to pulmonary colonization in cystic fibrosis. AB - Representative isolates of nonmucoid Pseudomonas aeruginosa were studied to investigate the hypothesis that mucinophilic and chemotactic properties in this species act as potential factors in the initial stages of pulmonary colonization in patients with cystic fibrosis (CF). Transmission electron microscopy with a surfactant monolayer technique was used in a novel manner to demonstrate the adhesion of all 10 P. aeruginosa strains examined to porcine gastric mucin and tracheobronchial mucin from a patient with CF. Control experiments showed that Escherichia coli K-12 and single representatives of Proteus mirabilis and Klebsiella aerogenes did not bind to these mucins. The Adler capillary technique, used to measure bacterial chemotactic response, showed that purified CF mucin acted as a chemoattractant for most P. aeruginosa strains, with the exception of the nonmotile mutant M2Fla- and the nonchemotactic mutant WR-5. The ability of the major sugar and amino acid components of mucin to act as chemoattractants was investigated. The degree of chemotaxis was strain specific; optimum chemotaxis was observed toward serine, alanine, glycine, proline, and threonine. No strain showed chemotaxis to N-acetylneuraminic acid, but all strains showed a strain dependent chemotactic response to the sugars L-fucose, D-galactose, N-acetyl-D galactosamine, and N-acetyl-D-glucosamine. These results provide new information on the mucinophilic and chemotactic properties of nonmucoid P. aeruginosa and support the hypothesis that these properties could play a role in the initial stages of pulmonary colonization in patients with CF. PMID- 2111281 TI - Interactions between adherent mononuclear cells and lymphocytes from granulomas of mice with schistosomiasis mansoni. AB - T-lymphocyte-adherent mononuclear cell interaction was analyzed in the vigorous and immunomodulated liver granulomas of Schistosoma mansoni-infected mice. Collagenase-dispersed granulomas contained 15% lymphocytes, 30% macrophages, 50% eosinophilis, and some neutrophils. Dispersed granuloma cells stimulated with concanavalin A or soluble worm egg antigens (SEA) did not proliferate unless plate-adherent, esterase-positive mononuclear cells were removed before culture. To analyze the granuloma adherent cell-mediated suppression, vigorous granuloma cell cultures partially depleted of adherent mononuclear cells were supplemented with indomethacin, catalase, superoxide dismutase, levamisole, and anti-murine alpha/beta interferon antiserum. In concanavalin A and SEA-stimulated cultures, only the addition of indomethacin or anti-alpha/beta interferon antiserum alleviated the adherent cell-mediated suppression of vigorous granuloma lymphocyte response. In contrast, these agents only minimally alleviated the suppressed response of SEA-stimulated, immunomodulated granuloma lymphocytes. Moreover, coculture of equal numbers of vigorous and immunomodulated granuloma cells partially depleted of adherent suppressor cells abrogated the alleviated response of vigorous granuloma lymphocytes. These findings indicate that, within the schistosome egg-induced vigorous granulomas, the adherent mononuclear cells exert regulation over lymphocyte responsiveness by alpha/beta-interferon and an indomethacin-sensitive, probably prostaglandin-mediated pathway. Within the immunomodulated granulomas, the adherent suppressor cell-mediated regulation of lymphocyte proliferation appears to play a lesser role. PMID- 2111282 TI - Strain differences in sensitivity of rats to Mycoplasma arthritidis ISR 1 infection are under multiple gene control. AB - At least 5 female rats from each of 24 inbred (ACI, AS, BDIX, BH, BN, BS, BUF, DA, LE, LEW, MWF, OM, SPRD-Cu3, W-Krypt, and WKY), RT1 congenic [BH.1L(LEW), LEW.1A(AVN), LEW.1C(WIST), LEW.1LV3(BH), LEW.1K(SHR), and LEW.1N(BN)], and F1 hybrid [(LEW x BN)F1, (LEW.1W x LEW.1A)F1, and (LEW x LEW.1W)F1] strains, representing eight independent major histocompatibility complex (MHC) haplotypes (a, b, c, dv1, k, l, n, and u) and five related RT1 haplotypes (av1, lv1, lv3, uv2, and uv3), were inoculated intravenously with Mycoplasma arthritidis, and the severity of the polyarthritis that developed was determined by estimating arthritis scores and weight reductions. The 24 inbred, congenic, and F1 hybrid rat strains differed considerably in their sensitivity to infection with M. arthritidis and in the severity of the polyarthritis that they developed. Statistical evaluation showed that in the acute phase (days 1 to 42 after infection) as well as in the chronic phase (days 39 to 121 after infection) of the disease, the means of the arthritis scores for the strains form a continuous variation without significant interruptions, with the very sensitive LEW rats, the RT1 congenic rats on LEW background, the F1 hybrids with LEW, and the MWF, BS, BH, and DA rats on one end and the resistant WKY, BUF, W-Krypt, LE, and OM rats on the other end. A continuous variation was also observed for the means of the growth rates. There were, however, no significant differences between the sensitive and the resistant rat strains in the antibody titers determined by complement fixation test and enzyme immunoassay. Heritabilities of arthritis scores were calculated for all strains (h2 = 0.39 to 0.62), for the RT1 congenic strains (h2 = 0.04 to 0.14), and for several strains with identical MHC genes (h2 = 0.61 to 0.93). The results show that non-MHC genes are probably responsible for the sensitivity of rats to infection with M. arthritidis. PMID- 2111284 TI - Production of the hexitol D-mannitol by Cryptococcus neoformans in vitro and in rabbits with experimental meningitis. AB - We studied the ability of Cryptococcus neoformans to produce the hexitol D mannitol in vitro and in rabbits with experimental meningitis. Twelve of twelve human isolates of C. neoformans produced D-mannitol in yeast nitrogen base plus 1% glucose and released D-mannitol into the medium. In a pilot study, pooled cerebrospinal fluid (CSF) from cortisone-treated rabbits given 3 x 10(7) C. neoformans H99 intracisternally contained more D-mannitol (identified by gas chromatography and enzymatically) than CSF from normal controls or cortisone untreated rabbits with self-limited meningitis. In a second experiment, cortisone treated rabbits given C. neoformans intracisternally had significantly higher CSF D-mannitol concentrations than controls given cortisone alone at 4, 6, and 8 days after infection. Moreover, log10 CSF D-mannitol correlated well with log10 CSF CFU (r = 0.81) and log10 CSF cryptococcal antigen titers (r = 0.78). Lastly, the initial volume of distribution and elimination half-life of D-mannitol given intracisternally to normal rabbits suggested that D-mannitol was distributed in total CSF and was removed by CSF bulk flow. Thus, C. neoformans produces D mannitol in vitro and in vivo, and D-mannitol is a quantitative marker for experimental cryptococcal meningitis. D-Mannitol produced by C. neoformans may also contribute to brain edema and interfere with phagocyte killing by scavenging hydroxyl radicals. PMID- 2111283 TI - Production and characterization of monoclonal antibodies against the lethal factor component of Bacillus anthracis lethal toxin. AB - The lethal toxin of Bacillus anthracis consists of two components, protective antigen and lethal factor. Protective antigen is cleaved after binding to cell receptors, yielding a receptor-bound fragment that binds lethal factor. Sixty-one monoclonal antibodies to the lethal factor protein have been characterized for specificity, antibody subtype, and ability to neutralize lethal toxin. Three monoclonal antibodies (10G3, 2E7, and 3F6) neutralized lethal toxin in Fisher 344 rats. However, in a macrophage cytolysis assay, monoclonal antibodies 10G3, 2E7, 10G4, 10D4, 13D10, and 1D8, but not 3F6, were found to neutralize lethal toxin. Binding studies showed that five of the monoclonal antibodies that neutralized lethal toxin in the macrophage assay (10G3, 2E7, 10G4, 10D4, and 13D10) did so by inhibiting the binding of lethal factor to the protective antigen fragment bound to cells. Monoclonal antibody 1D8, which was also able to neutralize lethal toxin activity after lethal factor was prebound to cell-bound protective antigen, only partially inhibited binding of lethal factor to protective antigen. Monoclonal antibody 3F6 did not inhibit the binding of lethal factor to protective antigen. A competitive-binding enzyme-linked immunosorbent assay showed that at least four different antigenic regions on lethal factor were recognized by these seven neutralizing hybridomas. The anomalous behavior of 3F6 suggests that it may induce a conformational change in lethal factor. Differences in neutralizing activity of monoclonal antibodies were related to their relative affinity and epitope specificity and the type of assay. PMID- 2111285 TI - A strong antibody response to the periplasmic C-terminal domain of the OmpA protein of Escherichia coli is produced by immunization with purified OmpA or with whole E. coli or Salmonella typhimurium bacteria. AB - We produced in Bacillus subtilis the complete, as well as the N-terminal two thirds, OmpA protein of Escherichia coli (called here Bac-OmpA and Bac-OmpA-dN, respectively). These Bac-OmpA proteins were used to examine the immunological properties of different parts of OmpA, free of lipopolysaccharide and other components of the outer membrane. The full-length Bac-OmpA was indistinguishable from the authentic protein isolated from E. coli (Coli-OmpA) both as immunogen and as antigen in enzyme immunoassay (EIA). The N-terminal Bac-OmpA-dN was a poor immunogen which gave rise to significantly lower titers of anti-OmpA antibody than did the full-length OmpA preparations. When used as an antigen in EIA, the Bac-OmpA-dN detected anti-OmpA antibody in serum samples from animals immunized with the full-length OmpA much less efficiently than did either Bac-OmpA or Coli OmpA. The periplasmic C-terminal domain therefore appears to be an immunodominant epitope of the purified OmpA protein. Also, when rabbits and mice were immunized with intact, live or dead E. coli, the antibody response detected by EIA with the full-length protein, Bac-OmpA, was much stronger than that detected with the N terminal two-thirds, Bac-OmpA-dN. Similar results were obtained with the OmpA of Salmonella typhimurium. Because the ompA gene of enterobacteria is highly conserved, the Bac-OmpA might be useful as a group-specific EIA antigen to diagnose diseases caused by members of the family Enterobacteriaceae. PMID- 2111286 TI - Inhibition of Rickettsia conorii growth by recombinant tumor necrosis factor alpha: enhancement of inhibition by gamma interferon. AB - Purified human recombinant tumor necrosis factor alpha (rTNF-alpha) inhibited the growth of Rickettsia conorii (Casablanca strain) in HEp-2 cell culture. The effect was observed when the cells were pretreated with rTNF-alpha or when rTNF alpha was added after adsorption of the rickettsiae. The inhibitory effect of rTNF-alpha on rickettsial growth was enhanced by gamma interferon. Cycloheximide had no effect on inhibition of the rickettsial yield, suggesting that de novo protein synthesis is not required for the inhibitory effect of rTNF-alpha. The addition of tryptophan partially abolished the inhibitory effect of rTNF-alpha and rTNF-alpha plus gamma interferon. PMID- 2111287 TI - The gene coding for protein p60 of Listeria monocytogenes and its use as a specific probe for Listeria monocytogenes. AB - The gene of Listeria monocytogenes that encodes a major extracellular protein (p60) was cloned in Escherichia coli. The gene was designated iap, as p60 was previously shown to represent an invasion-associated protein (M. Kuhn and W. Goebel, Infect. Immun. 57:55-61, 1989). The recombinant E. coli clone expressed p60, as shown by immunoblotting. The complete nucleotide sequence of iap was determined. The deduced amino acid sequence of p60 (484 amino acids) contains a putative N-terminal signal sequence of 27 amino acids and an extended repeat region consisting of 19 threonine-asparagine units. Hybridization with the entire iap gene revealed the presence of homologous sequences in most other Listeria species. In contrast, a 400-base-pair internal iap probe which contained the whole repeat region hybridized only with genomic DNA from L. monocytogenes. Four oligonucleotides previously described as specific probes for the detection of L. monocytogenes (A. R. Datta, B. A. Wentz, D. Shook, and M. W. Trucksess, Appl. Environ. Microbiol. 54:2933-2937, 1988) were shown to be part of the iap gene. PMID- 2111288 TI - A proteolytic enzyme secreted by Proteus mirabilis degrades immunoglobulins of the immunoglobulin A1 (IgA1), IgA2, and IgG isotypes. AB - Proteus mirabilis strains associated with human urinary tract infections have previously been shown to secrete an extracellular metalloproteinase which cleaves serum immunoglobulin A (IgA). The enzyme has now been purified to apparent homogeneity from culture supernatants of P. mirabilis 64676. The protease activity is associated with a 50-kilodalton (kDa) protein. Unlike that of the classic IgA1 proteases, the substrate specificity of the P. mirabilis protease has been found to extend to both sublcasses of IgA, IgG, and the nonimmunoglobulin substrates, secretory component and casein. Cleavage of IgA1 and IgA2 by the P. mirabilis protease yielded fragments on sodium dodecyl sulfate polyacrylamide gel electrophoresis whose sizes were consistent with a cleavage site outside the hinge region. Both secretory IgA1 and IgA2 were also cleaved by P. mirabilis protease, although the secretory IgA2 molecule was less readily cleaved than secretory IgA1. Free and IgA-bound secretory components were degraded to some extent by P. mirabilis protease. Cleavage of IgG, however, occurred at the hinge region as a two-stage process. The first stage was pepsinlike and generated an F(ab')2 fragment of 120 kDa and a small pFc fragment detected on nonreduced polyacrylamide gels. In the second stage, the F(ab')2 product was cleaved to yield papainlike Fab and Fc fragments, visualized as a diffuse band of 40 to 50 kDa. PMID- 2111289 TI - Proteolysis of Clostridium perfringens type A enterotoxin during purification. AB - The small satellite bands of enterotoxin frequently seen in polyacrylamide gels following purification of Clostridium perfringens enterotoxin were found to be due to endogenous protease activity and were not present if phenylmethylsulfonyl fluoride (PMSF; 1 mM) and EDTA (10 mM) were used in the purification protocol. The use of PMSF was avoided by passing gel filtration-purified enterotoxin material through DEAE-Sephacel. This modified protocol resulted in an 11.4-fold purification of enterotoxin and a 26.8% yield. Contrary to previous reports (B. R. Dasgupta and M. W. Pariza, Infect. Immun. 38: 592-597, 1982), if PMSF and EDTA were included during purification, we were unable to detect the novel enterotoxin ET-1 produced by strain NCTC 10240. C. perfringens proteases cleaved homogeneous enterotoxin into two additional fragments, suggesting that ET-1 was a product of endogenous protease action during purification. PMID- 2111290 TI - Selecting substance abusers for long-term treatment. AB - From a population of indigent alcoholics, those selected for long-term treatment were compared with those who were not selected on demographics, personality, and drinking history. A discriminate function analysis accurately classified 84%. The graded stepwise discriminatory variables for selection for long-term treatment were: less extreme MMPI scores on psychopathic deviance, depression, dependency, and hypochondriasis; higher scores on control and ego strength; less severe alcohol history; and slightly higher education. Only 52% of those selected completed long-term treatment. Variables associated with selection for long-term treatment found here are consistent those found associated with treatment completion in other studies. Systematic selection for these variables should improve long-term treatment completion rates. PMID- 2111291 TI - The influence of prolonged stable methadone maintenance treatment on mortality and employment: an 8-year follow-up. AB - A cohort of 169 opiate drug addicts was followed for 8 years. The mortality rate was 3.3 per year. The average lethality per observation year was found to be higher than in other studies. The treatment with methadone was unstable and only 11% had received stable prolonged maintenance treatment. It is not possible to reject a model that described increasing mortality rates neither as a function of falling methadone maintenance treatment nor as a function of socially unstable addicts contra stable addicts. Unemployment was high in the cohort (87%), and no relationship could be demonstrated between methadone maintenance treatment and employment. PMID- 2111292 TI - Long-term effects on lipid metabolism of weight reduction on lactovegetarian and mixed diet. AB - The effects of two dietary weight reduction programmes (1200 kcal/day) on lipid metabolism were followed for one year in moderately obese subjects. The groups consisted of lactovegetarian (n = 31), mixed diet (n = 37) and control (n = 42) groups. Serum triglyceride levels decreased rapidly during the first two weeks (46 per cent on average) especially in the mixed diet group, and this change was still statistically significant at 6 and 12 months after the beginning of the study. Serum total cholesterol levels also decreased rapidly in the beginning, but at 6 and 12 months the change was no longer statistically significant. After a small initial decrease HDL cholesterol levels appeared to increase towards the end of the study year. This increase was more marked in men (18.6 per cent at 6 months) than in women, and in the mixed diet group than in the lactovegetarian group (P less than 0.05 between the groups). The HDL/total cholesterol ratio increased rapidly in the beginning of the weight reduction and practically remained at the elevated (12-16 per cent) level during the whole follow-up. This increase was also more apparent in men than in women, and in the mixed diet group than in the lactovegetarian group. The changes in HDL subfractions, HDL2 and HDL3, paralleled those seen in the HDL cholesterol levels. Similarly the alterations in apolipoproteins A-I and B resembled those of the HDL and total cholesterol levels. The activity of adipose tissue lipoprotein lipase decreased drastically (about 50 per cent) at the beginning of the weight reduction, while at 6 and 12 months the mean activities were higher than the initial levels. This was also seen in the LPL activity when measured in post-heparin plasma. The activity of post-heparin plasma hepatic lipase decreased clearly at both 6 (P less than 0.001) and 12 months (P less than 0.01) in the mixed diet group, whereas no change was found in the lactovegetarian group. The ratio of subscapular to triceps skinfold reduced significantly (P less than 0.01) in women but not in men during the intervention period. Our study shows that in moderately overweight subjects weight reduction with the aid of a low-calorie dietary programme results in favourable responses in lipid metabolism many months after the cessation of the weight reduction programme. These responses appear to be stronger in subjects following mixed diet than in those attempting to follow a lactovegetarian diet. PMID- 2111293 TI - Pulmonary function and energy expenditure after marked weight loss in obese women: observations before and one year after gastric banding. AB - Pulmonary function and pulmonary gas exchange at rest, and during and after a standard exercise load of 500 kpm in 1 min on bicycle ergometer were studied in 34 women with severe, uncomplicated obesity, aged 37.8 (20-59) years, before and 1 year after gastric banding, resulting in a weight loss from 113.2 (84-156) to 81.7 (60-110) kg. Following the weight loss, TLC and VC rose from 93 and 94 per cent of expected to 98 and 101 per cent, respectively. FRC, ERV and FRC/TLC rose more markedly from 77, 64 and 83 per cent to 98, 109 and 99 per cent. IC fell from 108 to 99 per cent. RV and RV/TLV remained unchanged. FEV1.0 rose from 97 to 103 per cent, while MVV rose from 102 to 112 per cent, i.e. above normal. TLCO and PaCO2 remained unchanged, at 90 and 95 per cent, whereas PaO2 rose from 86 to 91 per cent. Resting O2 intake (VO2) decreased from 147 to 115 per cent of the expected for normal weight women, while VO2/BSA decreased from 113 to 99 per cent, the changes being greater than expected from commonly used formulas for prediction of metabolic rate. O2 cost of work (EO2) decreased from 142 to 105 per cent. Resting ventilation (V) declined from 136 to 113 per cent, while ventilatory cost of work (EV) decreased from 142 to 105 per cent. CO2 recovery time after work (CO2RT) decreased from 121 to 100 per cent, while the ratios CO2RT to EO2 and to extra CO2 output of work (ECO2) rose slightly. Thus, the loss of weight led to increased filling of the lungs, improved dynamic function, reduced ventilation/perfusion disturbances and greater than expected reduction of energy expenditure, both at rest and exercise. In the obese state there was no evidence of alveolar hypoventilation or impaired ventilatory control. The beneficial effect of weight reduction on the exertional dyspnea included a combination of marked reduction of ventilatory demands and moderate rise in ventilatory capacity. PMID- 2111294 TI - The relegation of patients to long-term care: the Kuakini experience. PMID- 2111295 TI - A new method for calculating the distribution of radioactivity in man measured with a whole-body counter. AB - A whole-body counter with a scanning bed and two opposite (antero-posterior) probes was used to obtain profiles of count rates of radioactivity held in the whole body. The distribution of the activity in the patient was calculated by solving an overdetermined system (more equations than unknowns) of linear equations with the Chebyshev method, the least-squares method, and an iterative method. The iterative method gave the best results, especially in the case of distributions with peaks of radioactivity. Some in-vivo applications of the method are presented. PMID- 2111296 TI - Opening a new critical care nursing unit during a nursing shortage: recruitment and retention strategies. AB - A need for an interventional cardiology patient care unit was identified. Obtaining qualified registered nurses to staff a new unit during a nursing shortage was viewed as a challenge. Staff nurse involvement was sought in all phases of development and was a key component in our success. Using a variety of recruitment and retention strategies, we met the challenge and opened the unit on time. PMID- 2111297 TI - Radioiodinated ligands for the estrogen receptor: tissue distribution of 17 alpha [125I]iodovinylestradiol derivatives in normal and tumor-bearing adult female rats. AB - A series of three 125I-labeled 17 alpha-iodovinylestradiol derivatives previously demonstrated to have a selectivity for estrogen receptor tissues in immature female rats were selected for further evaluation in adult female rats. In normal adult female rats, the iodovinyl analogs of moxestrol (IV beta ME2), and moxestrol-3-O methyl ether (IV beta ME2-3-OMe) demonstrated high uterine uptake (0.296-0.437 and 0.135-0.199%ID-kg/g) and selectivity (10-18:1) over the 6 h time period. Subsequent evaluation in two tumor models indicated that [125I]V beta ME2 also possessed the highest tumor uptake and selectivity in the adult female rats bearing the estrogen responsive 9,10-dimethyl-1,2-benzanthracene(DMBA)-induced mammary tumors and that this was receptor mediated. An estrogen independent tumor, the transplanted Walker 256 mammary adenocarcinoma, showed no selectivity of radioligand uptake compared with nontarget tissues. The results suggest the applicability of this agent to the in vivo detection and characterization of estrogen responsive tumors in man. PMID- 2111298 TI - A comparison of 131I-labeled antibodies, 2-deoxy-2-[18F]fluoro-D-glucose and 68Ga EDTA in the imaging of human tumor xenografts in nude mice. AB - Three different biological properties--glucose metabolism, gallium imaging and antigen-antibody interaction--have been targeted to image human tumor xenografts implanted in nude mice. Seventy-two experiments were performed in 25 nude mice. Two types of human tumors were used: colorectal carcinoma SW 1116 and melanoma WM 9. Immunoscintigraphic studies produced the highest tumor sampling and confirmed earlier findings that F(ab')2 fragments generate better tumor images than whole antibodies. PMID- 2111299 TI - Analysis of competitive interactions in triocultures of Drosophila melanogaster. AB - Competitive interactions in complex mixtures of genotypes have rarely been studied despite their obvious importance in both natural and commercial populations. Here, we describe a procedure for the analysis of competition in tripartite mixtures of Drosophila melanogaster genotypes. We have utilised a substitution design coupled with a yield-density regression analysis which describes intra- and inter-genotypic competitive effects in terms of simple linear parameters. The experimental design allows any of the competitors to be considered as the primary or indicator genotype and also incorporates variation in the relative proportions of the two associate competitors. The regression parameters are used to derive estimates of the competitive pressure exerted by each associate on the indicator genotype and also the response or sensitivity of the indicator to the competitive pressure which it faces in mixed culture. The results indicate that the joint pressure exerted by the paired associate genotypes in trioculture is equal to the sum of the individual pressures of those associates. This additive relationship holds for a variety of indicator genotypes isolated from the Texas population and appears to be a general property of Drosophila competition. We identified one indicator genotype which consistently departed from this relationship although additivity of joint pressures could be restored in combination with particular associate genotypes. The possible role of larval interference in the determination of these interactions is discussed. PMID- 2111300 TI - The biometrical genetics of competitive parameters in Drosophila melanogaster. AB - Despite the importance of competition as an evolutionary determinant in natural populations there have been few studies of the genetical control of competitive ability. Here, we report the results of a biometrical analysis of four continuously varying traits which, between them, describe the competitive interactions in mixed cultures of Drosophila melanogaster. The analysis involved the parental, F1, F2 and backcross generations (including all reciprocals) derived from crosses between two highly inbred lines isolated from the Texas population of D. melanogaster. The competitive performance of each genotype in monoculture and in duoculture with a phenotypically distinct tester were assessed using a yield-density regression analysis. Appropriate genetic models were fitted using a variance weighted least squares procedure and the resulting genetic components of the generation means used to define the genetical architecture of competition. Of the four competitive parameters investigated here the e-value, which describes the competitive performance of the indicator genotype at a fixed reference density, was found to be determined by simple additive genetic effects with no evidence of significant dominance. Conversely, competitive performance in monoculture (intra-genotypic competition) did display a significant net dominance component and the observed values in the F1 and parental generations indicated some degree of heterosis. Of the two competitive parameters determining performance in duoculture (inter-genotypic sensitivity and inter-genotypic pressure) the former was found to have a complex genetic determination involving not only additive and dominance components of the progeny's own genotype but also dominance components of the F1 maternal genotypes. There were also additive dominance and dominance-dominance non-allelic interactions. Heterosis was evident, determined both by the progeny's own genotype and by one of the F1 maternal genotypes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111301 TI - Developmental anomalies in Drosophila hybrids are apparently caused by loss of microchromosome. AB - Hybrids produced by crossing Drosophila virilis females to D. lummei males suffer from many developmental anomalies; the reciprocal hybridization yields normal offspring. Genetic analysis reveals that these anomalies involve a maternal effect: whether or not an individual will show an anomaly depends upon his mother's nuclear genotype. Several lines of evidence suggest that the proximal cause of the anomalies is the elimination of the D. lummei microchromosome (chromosome 6) from hybrids. Loss of the D. lummei microchromosome in this hybridization is known to involve a maternal effect (Evgen'ev, 1973), as mitosis in early development is under the control of maternally-acting genes. PMID- 2111302 TI - What is your diagnosis? An air-filled circular lesion within the caudodorsal portion of the thorax. PMID- 2111303 TI - Hemicellulases of Bacillus species: preliminary comparative studies on production and properties of mannanases and galactanases. AB - A range of Bacillus subtilis strains and other Bacillus species were screened for mannanase, beta-mannosidase and galactanase activities. Maximum mannanase activity, 106.2 units/ml, was produced by B. subtilis NRRL 356. beta-Mannosidase and galactanase activities from all strains were relatively low. The effect of carbon and nitrogen source on mannanase and galactanase production by B. brevis ATCC 8186, B. licheniformis ATCC 27811, B. polymyxa NRRL 842 and B. subtilis NRRL 356 was investigated. Highest mannanase production was observed in the four strains tested when the mannan substrate, locust bean gum, was used as carbon source. Induction was most dramatic in the case of B. subtilis NRRL 356 where only basal enzyme levels were produced in the presence of other carbon sources. beta-Mannosidase was induced in the four Bacillus cultures by locust bean gum. Results indicated that galactose acted as an inducer for production of galactanase. Organic and inorganic nitrogen sources resulted in induction of high mannanase titres in B. subtilis. Highest galactanase activity was produced by each organism in media containing sodium nitrate as nitrogen source. Mannanases from B. brevis, B. licheniformis, B. polymyxa and B. subtilis retained 100% residual activity after a 3 h incubation at 65 degrees C, 65 degrees C, 60 degrees C and 55 degrees C respectively. Galactanases retained more than 95% activity at 55 degrees C after 3 h. The pH optima of mannanases ranged from 6.5 6.8 whereas galactanases ranged from 5.1 in the case of B. brevis to 7.0 for B. polymyxa. PMID- 2111304 TI - The survival and transfer of microbial contamination via cloths, hands and utensils. AB - Survival and transfer of bacteria from laminated surfaces and cleaning cloths were investigated under laboratory conditions. Drying produced substantial reductions in numbers of recoverable organisms and achieved satisfactory decontamination of clean laminate surfaces. On soiled surfaces and on clean and soiled cloths, Gram-positive and some Gram-negative species survived for up to 4 h, and in some cases up to 24 h. Where contaminated surfaces or cloths came into contact with the fingers, a stainless steel bowl, or a clean laminate surface, organisms were transferred in sufficient numbers to represent a potential hazard if in contact with food. PMID- 2111305 TI - Respiratory muscle responses to changes in chemoreceptor drive in infants. AB - Upper airway muscles and the diaphragm may have different quantitative responses to chemoreceptor stimulation. To compare the respiratory muscle responses to changes in CO2, 10 ventilator-dependent preterm infants (gestational age 28 +/- 1 wk, postnatal age 40 +/- 6 days, weight 1.4 +/- 0.1 kg) were passively hyperventilated to apnea and subsequently hypoventilated. Electromyograms from the genioglossus, alae nasi, posterior cricoarytenoid, and diaphragm were recorded from surface electrodes. Apneic CO2 thresholds of all upper airway muscles (genioglossus 46.8 +/- 4.3 Torr, alae nasi 42.4 +/- 3.6 Torr, posterior cricoarytenoid 41.6 +/- 3.2 Torr) were higher than those of the diaphragm (38.8 +/- 2.6 Torr, all P less than 0.05). Above their CO2 threshold levels, responses of all upper airway muscles appeared proportional to those of the diaphragm. We conclude that nonproportional responses of the respiratory muscles to hypercapnia may be the result of differences in their CO2 threshold. These differences in CO2 threshold may cause imbalance in respiratory muscle activation with changes in chemical drive, leading to upper airway instability and obstructive apnea. PMID- 2111306 TI - Measurement of intracellular pH in hamster diaphragm by absorption spectrophotometry. AB - The regulation of intracellular pH (pHi) is important in controlling muscle contraction. In these experiments, a spectrophotometric method of determining pHi was developed, and the method was then used to study muscle pHi regulation during CO2-induced changes in extracellular pH (pHb). Studies were performed in vitro on 27 diaphragm muscle strips obtained from adult hamsters. pHi was measured from the ratio of the absorbances of the acid (lambda = 530 nm) and alkaline (lambda = 460 nm) forms of a vital dye, neutral red, using the unstained diaphragm spectrum as a reference blank. A standard neutral red calibration curve constructed from eight diaphragm muscle homogenates indicated that the absorbance ratio was highly linear, with pH over the range 6.00-8.00. In intact muscle strips gassed with 95% O2-5% CO2, pHb was 7.45 +/- 0.03 (SE) and pHi was 7.00 +/- 0.01 (SE). When the muscle was aerated with CO2 concentrations from 3 to 30%, pHb and pHi changed rapidly and reached a steady state in 10-15 min. However, when pHb ranged from 6.80-7.80, pHi changed little from the value observed when pHb was 7.40. When pHb was less than 6.80 or greater than 7.80, changes in pHi and pHb were quantitatively similar. The results suggest that, in the isolated diaphragm, overall pHi is stable and effectively buffered over a wide range of CO2-induced changes in buffer solution pH. PMID- 2111307 TI - Dynamics of the ventilatory response to central hypoxia in cats. AB - The dynamics of the effect of central hypoxia on ventilation were investigated by the technique of artificial perfusion of the brain stem in alpha-chloralose urethan-anesthetized cats. A two-channel roller pump and a four-way valve allowed switching the gas exchanger into and out of the extracorporeal circuit which controlled the brain stem perfusion. When isocapnic hypoxia (arterial PO2 range 18-59 Torr) was limited to the brain stem, a decline in ventilation was consistently found. In 12 cats 47 steps into and 48 steps out of central hypoxia were made. The ventilatory response was fitted using least squares with a model that consisted of a latency followed by a single-exponential function. The latencies for the steps into and out of hypoxia were not significantly different (P = 0.14) and were 32.3 +/- 4.0 and 25.1 +/- 3.6 (SE) s, respectively. The time constant for the steps into hypoxia (149.7 +/- 8.5 s) was significantly longer (P = 0.0002) than for the steps out of hypoxia (105.5 +/- 10.1 s). The time constants for the increase and decrease in ventilation after step changes in the central arterial PCO2 found in a previous study (J. Appl. Physiol. 66: 2168-2172, 1989) were not significantly different (P greater than 0.2) from the corresponding time constants in this study (for 7 cats common to both studies). Theories of the mechanisms behind hypoxic ventilatory decline need to account for the long latency, the similarity between the time constants for the ventilatory response to O2 and CO2, and the differences between the time constants for increasing and decreasing ventilation. PMID- 2111308 TI - Calcium chelators induce bronchoconstriction in the canine lung periphery. AB - We studied the mechanism by which Na2EDTA, a divalent cation chelator, induces bronchoconstriction in the lung periphery of mongrel dogs as a model of nonspecific small airway hyperresponsiveness. Using a wedged bronchoscope technique, we measured collateral system resistance (Rcs) before and after challenges with aerosolized Na2EDTA. An isotonic solution (4% Na2EDTA, 0.28 osmol/kg) increased Rcs 91 +/- 21%. Na2EDTA increased Rcs in a dose-dependent fashion after challenges of increasing concentration (0, 1, 3, and 6%) or duration (15, 30, 60, and 90 s) with 6% Na2EDTA. Atropine (1 mg/kg iv) significantly (P = 0.01) attenuated the response to an aerosol challenge with distilled H2O. Atropine did not significantly (P = 0.35) alter the response to a challenge with 4% Na2EDTA. Challenge with 6% Na2EDTA (0.42 osmol/kg) increased Rcs to a significantly greater (P less than 0.01) extent than did challenge with 6% CaNa2EDTA (0.37 osmol/kg, 250 +/- 55 vs. 29 +/- 11%, respectively). We conclude that Na2EDTA induces bronchoconstriction in the canine lung periphery in a dose-dependent fashion. As suggested by the Na2EDTA-CaNa2EDTA comparison, hyperosmolality of the solution alone cannot explain this phenomenon. The mechanism does not depend on muscarinic activity and appears to involve chelation of calcium. PMID- 2111309 TI - Fluorescence location of RVLM kainate microinjections that alter the control of breathing. AB - Kainic acid (4.7 mM) applied to the rostral ventrolateral medulla (RVLM) surface decreases phrenic output, CO2 sensitivity, and blood pressure in chloralose urethan-anesthetized, vagotomized, paralyzed, glomectomized, servoventilated cats. In this study using the same preparation, bilateral 50- to 100-nl kainate injections just below the RVLM surface better localized these responses topographically. The physiological responses to unilateral 10-nl kainate injections were then correlated with anatomic location determined by fluorescent microbeads (0.5 micron diam). Many sites were associated with no effect, a few rostral and caudal sites with increased phrenic activity, and cluster of sites with decreased phrenic activity often to apnea, decreased CO2 sensitivity, and decreased responses to carotid sinus nerve stimulation. Blood pressure was unaffected. These sites, within 400 microns of the surface, were ventral to the facial nucleus, ventrolateral to the nucleus paragigantocellularis lateralis, caudal to the superior olive, and rostral to the retrofacial nucleus. They appeared to be within the recently described retrotrapezoid nucleus, which contains cells with respiratory-related activity and projections to the dorsal and ventral respiratory groups. Cells within this site appear able to provide tonic input to respiration and to affect peripheral and central chemoreception. PMID- 2111310 TI - Unchanged in vivo P50 at high altitude despite decreased erythrocyte age and elevated 2,3-diphosphoglycerate. AB - We measured hematological and erythrocyte O2 transport parameters in whole blood and density-separated erythrocytes in 11 mountaineers before and during 5 days of exposure to high altitude (4,559 m). We determined the in vivo (arterial pHblood and PCO2) and standard (pHblood = 7.4, PCO2 = 40 Torr) O2 tension at 50% O2 saturation of hemoglobin and (P50,vv and P50,st) and Bohr coefficients (BC) for fixed acid (H+) and CO2 and examined the contribution of the altered average age of circulating erythrocytes due to the stimulation of erythropoiesis on whole blood 2,3-diphosphoglycerate (2,3-DPG) and P50,st. At altitude, whole blood P50,vv remained almost unchanged, whereas P50,st and 2,3-DPG increased significantly (+4 Torr; 3.5 mumol/g hemoglobin). BCCO2 was elevated significantly at altitude. Serum erythropoietin increased transiently fourfold, iron utilization increased, and serum iron decreased by 66%. Reticulocyte counts increased, but other hematological parameters were unchanged. In density separated erythrocytes, P50,st and 2,3-DPG increased with decreasing cell density but were higher in fractions with comparable reticulocyte counts in cells prepared at altitude than in those from control studies. Our data show that, despite the increase in 2,3-DPG and the decrease in average erythrocyte age, the in vivo hemoglobin-O2 affinity remains unchanged. P50,st values reflect the elevation of 2,3-DPG, and approximately 50% of the increase in both parameters can be ascribed to the increase in the number of reticulocytes and young erythrocytes. PMID- 2111311 TI - Rat skeletal muscle mitochondrial [Ca2+] and injury from downhill walking. AB - The purpose of this study was to evaluate the relationship between mitochondrial Ca2+ concentration (MCC) and the extent of muscle injury in rats that have performed prolonged downhill walking (eccentric exercise). MCC was used as an indicator of elevated [Ca2+] in the muscles, and injury was estimated from histochemical analysis of muscle cross sections by determining the numbers of intact fibers per unit area in the muscles. Elevations in MCC in the soleus and vastus intermedius muscles over time postexercise were inversely related (P less than 0.05) to the number of intact fibers per square millimeter in the respective muscles after downhill walking. Verapamil administration attenuated the elevation in MCC and injury in histochemical sections resulting from the downhill walking in soleus muscle, but intraperitoneal injection of the chelators EDTA or ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'- tetraacetic acid significantly attenuated the increases in MCC and injury to both the vastus intermedius and soleus muscles in the downhill walkers. The chelators appear to exert their "protective" effects within the specific muscles that show the injury and do not significantly affect serum [Ca2+]. It is concluded that increases in MCC occur during exercise-induced fiber injury and that elevations in cellular Ca2+ may have a role in the etiology of the injury process. PMID- 2111312 TI - Sensitization of group III muscle afferents to static contraction by arachidonic acid. AB - The afferent arm of the reflex are responsible for the pressor response to static contraction is comprised of group III and IV fibers. The nature of the contraction-induced stimulus activating these fibers remains unclear. Evidence suggests that most group III afferents are sensitive to mechanical stimuli, whereas most group IV afferents are sensitive to metabolic stimuli. Recently, in anesthetized cats, stimulation of group III mechanoreceptors has been shown to have a role in the reflex pressor response to static contraction. In skin, the sensitivity of thin fiber mechanoreceptors to distortion of their receptive fields has been shown to be increased by both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. Therefore, in barbiturate-anesthetized cats we recorded the responses of group III muscle afferents to static contraction before and after arachidonic acid (1-2 mg ia) and/or indomethacin (5 mg/kg iv). Arachidonic acid increased the responses of group III afferents (n = 11) to contraction by 265% (from 0.17 +/- 0.07 to 0.62 +/- 0.24 impulses/s; P less than 0.025). Indomethacin decreased the responses of group III afferents (n = 9) to contraction by 61% (from 1.00 +/- 0.37 to 0.39 +/- 0.16 impulses/s; P less than 0.025). Arachidonic acid given after indomethacin increased the responses of two of four group III afferents to contraction. We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism sensitize group III muscle afferents to static contraction. PMID- 2111313 TI - Effect of sustained hypoxia on ventilatory response to CO2 in normal adults. AB - In adult humans the ventilatory response to sustained hypoxia is biphasic, characterized by an early increase followed by a decline to an intermediate plateau. Recently, we have shown that this decrease in hypoxic sensitivity is long lasting, because up to 1 h of room air breathing is required for complete recovery of the initial hypoxic response (J. Appl. Physiol. 64: 521-528, 1988). It is not known whether this posthypoxia decrease in ventilatory response is general or specific only to hypoxic stimuli. We therefore examined responses to CO2 before and after hypoxia. The ventilatory response to 5 min of normoxic CO2 breathing was evaluated in eight normal adults on 2 days: 5 min before and after 25 min of normocapnic hypoxia (arterial O2 saturation +/- 80%) and 5 min before and after 25 min of room air breathing (control day). During hypoxia, ventilation (VI), after an initial increase, declined significantly. At the end of hypoxia, abrupt exposure to room air transiently dropped VI to values that were significantly below base line. On each experimental day, the first and second exposure to CO2 increased ventilation by a similar amount, averaging, respectively, 8.46 +/- 0.9 and 8.84 +/- 0.92 (SE) l/min on the hypoxic day and 8.24 +/- 0.96 and 7.65 +/- 0.94 l/min on the control day. All the hypercapnic increases of VI were accomplished through similar changes of breathing pattern with similar time courses. We conclude that sustained hypoxia does not affect the ventilatory response to CO2, but it selectively depresses hypoxic sensitivity. PMID- 2111314 TI - Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in men. AB - To assess the effects of endurance training on plasma glucose kinetics during moderate-intensity exercise in men, seven men were studied before and after 12 wk of strenuous exercise training (3 days/wk running, 3 days/wk cycling). After priming of the glucose and bicarbonate pools, [U-13C] glucose was infused continuously during 2 h of cycle ergometer exercise at 60% of pretraining peak O2 uptake (VO2) to determine glucose turnover and oxidation. Training increased cycle ergometer peak VO2 by 23% and decreased the respiratory exchange ratio during the final 30 min of exercise from 0.89 +/- 0.01 to 0.85 +/- 0.01 (SE) (P less than 0.001). Plasma glucose turnover during exercise decreased from 44.6 +/- 3.5 mumol.kg fat-free mass (FFM)-1.min-1 before training to 31.5 +/- 4.3 after training (P less than 0.001), whereas plasma glucose clearance (i.e., rate of disappearance/plasma glucose concentration) fell from 9.5 +/- 0.6 to 6.4 +/- 0.8 ml.kg FFM-1.min-1 (P less than 0.001). Oxidation of plasma-derived glucose, which accounted for approximately 90% of plasma glucose disappearance in both the untrained and trained states, decreased from 41.1 +/- 3.4 mumol.kg FFM-1.min-1 before training to 27.7 +/- 4.8 after training (P less than 0.001). This decrease could account for roughly one-half of the total reduction in the amount of carbohydrate utilized during the final 30 min of exercise in the trained compared with the untrained state. PMID- 2111315 TI - Molecular basis of hemophilia. PMID- 2111316 TI - Disulfide bridge structure of ascidian trypsin inhibitor I: similarity to Kazal type inhibitors. AB - The primary structures of ascidian trypsin inhibitors (iso-inhibitors I and II) were reported in the preceding paper (Kumazaki, T. et al. (1990) J. Biochem. 107, 409-413). Both of them have eight half-cystines in a molecule composed of 55 amino acid residues with a sequence showing no extensive homology to other known protease inhibitors. To locate the four disulfide bridges in the molecule, native inhibitor I was digested with thermolysin to yield cystine-containing peptides. The peptides were separated from each other by reversed-phase HPLC. A core peptide still containing six closely located half-cystines (e.g. -Cys-Arg-Cys and -Cys-Cys-) was further digested with Streptomyces griseus trypsin for cleavage of the Arg-Cys bond. On the other hand, the Cys-Cys bond was split by applying manual Edman degradation to the core peptide. Amino acid composition analyses of the resulting cystine peptides allowed us to define the whole disulfide bridge structure in the parent molecule. The topological relation between the disulfide loops and the reactive site suggested that the ascidian trypsin inhibitor may be classified as a member of the Kazal-type inhibitor family. PMID- 2111317 TI - Calcium stimulates ATP-Mg/Pi carrier activity in rat liver mitochondria. AB - Adenine nucleotide transport over the carboxyatractyloside-insensitive ATP-Mg/Pi carrier was assayed in isolated rat liver mitochondria with the aim of investigating a possible regulatory role for Ca2+ on carrier activity. Net changes in the matrix adenine nucleotide content (ATP + ADP + AMP) occur when ATP Mg exchanges for Pi over this carrier. The rates of net accumulation and net loss of adenine nucleotides were inhibited when free Ca2+ was chelated with EGTA and stimulated when buffered [Ca2+]free was increased from 1.0 to 4.0 microM. The unidirectional components of net change were similarly dependent on Ca2+; ATP influx and efflux were inhibited by EGTA in a concentration-dependent manner and stimulated by buffered free Ca2+ in the range 0.6-2.0 microM. For ATP influx, increasing the medium [Ca2+]free from 1.0 to 2.0 microM lowered the apparent Km for ATP from 4.44 to 2.44 mM with no effect on the apparent Vmax (3.55 and 3.76 nmol/min/mg with 1.0 and 2.0 microM [Ca2+]free, respectively). Stimulation of influx and efflux by [Ca2+]free was unaffected by either ruthenium red or the Ca2+ ionophore A23187. Calmodulin antagonists inhibited transport activity. In isolated hepatocytes, glucagon or vasopressin promoted an increased mitochondrial adenine nucleotide content. The effect of both hormones was blocked by EGTA, and for vasopressin, the effect was blocked also by neomycin. The results suggest that the increase in mitochondrial adenine nucleotide content that follows hormonal stimulation of hepatocytes is mediated by an increase in cytosolic [Ca2+]free that activates the ATP-Mg/Pi carrier. PMID- 2111318 TI - Alternative promoter and 5' exon generate a novel Gs alpha mRNA. AB - Several species of mRNA have been shown to encode the alpha subunit of the stimulatory GTP-binding regulatory protein, Gs alpha. The various Gs alpha mRNAs are generated through alternative splicing of a single precursor RNA and through the use of alternative acceptor splice sites. We now report the existence of a Gs alpha mRNA that uses a previously unidentified promoter and leading exon (termed exon 1'). In both the canine and human Gs alpha genes, exon 1' is located 2.5 kilobases 5' of exon 1. Exon 1' does not contribute an in-frame ATG, and thus its mRNA encodes a truncated form of Gs alpha. Initiation of translation is predicted to begin at an AUG in exon 2, as demonstrated both by in vitro translation and COS cell expression studies. PMID- 2111319 TI - A prostaglandin E receptor coupled to a pertussis toxin-sensitive guanine nucleotide regulatory protein in rabbit cortical collecting tubule cells. AB - At different concentrations, prostaglandin E2 (PGE2) can either stimulate or inhibit cAMP formation in freshly isolated rabbit cortical collecting tubule (RCCT) cells, but in cultured RCCT cells PGE2 can only stimulate cAMP synthesis (Sonnenburg, W. K., and Smith W. L. (1989) J. Biol. Chem. 263, 6155-6160). Here, we report characteristics of [3H]PGE2 binding to membrane receptor preparations from both freshly isolated and cultured RCCT cells. [3H]PGE2 binding to membranes from freshly isolated RCCT cells was saturable and partially reversible. Equilibrium binding analyses indicated that in the absence of guanosine 5'-3-O (thio)triphosphate (GTP gamma S) there is a single class of PGE2 binding sites (KD = 4.2 +/- 0.4 nM; Bmax = 583 +/- 28 fmol/mg); in the presence of 100 microM GTP gamma S, there is also only one class of binding sites but with a somewhat lower KD = 1.2 +/- 0.5 nM (Bmax = 370 +/- 40 fmol/mg). This stimulatory effect of GTP gamma S was blocked by pretreatment of the freshly isolated RCCT cells with pertussis toxin. The relative affinities of prostanoids for the [3H]PGE2-binding site were determined to be 17,18,19,20-tetranor-16-phenoxy-PGE2 methylsulfonylamide (sulprostone) approximately PGE2 approximately PGE1 approximately 16,16-dimethyl-PGE2 greater than carbacyclin approximately PGF2 alpha greater than PGD2. This is the order of potency with which prostaglandins inhibit arginine vasopressin-induced cAMP formation in fresh RCCT cells. Interestingly, [3H]PGE2 binding to membranes from cultured cells, which, unlike fresh cells, fail to show an inhibitory response to PGE2, was only 10-20% of that observed with membranes from fresh cells; moreover, binding of [3H]PGE2 to membranes from cultured cells was neither stimulated by GTP gamma S nor inhibited by sulprostone. The prostanoid binding specificities and the unusual pertussis toxin-sensitive, stimulatory effect of GTP gamma S on binding of [3H]PGE2 to membranes from freshly isolated RCCT cells are characteristics shared by a Gi linked PGE receptor from renal medulla (Watanabe, T., Umegaki, K., and Smith, W. L. (1986) J. Biol. Chem. 261, 14340-14349). Our results suggest that the [3H]PGE2 binding site of freshly isolated RCCT cells is the PGE receptor which is coupled to a Gi to attenuate arginine vasopressin-induced cAMP synthesis in the renal collecting tubule. PMID- 2111320 TI - Biosynthesis of the cell surface sialomucin complex of ascites 13762 rat mammary adenocarcinoma cells from a high molecular weight precursor. AB - Cell surfaces of metastatic 13762 ascites rat mammary adenocarcinoma cells are covered with a sialomucin complex composed of the high Mr sialomucin ASGP-1 (approximately 600,000) and a concanavalin A-binding, integral membrane glycoprotein ASGP-2 (120,000). Antibodies prepared against ASGP-2 and deglycosylated ASGP-1 react on immunoblots of ascites cells or their isolated microvilli with the Mr = 120,000 species and the high Mr sialomucin, respectively. No cross-reactivity was observed. Under complex dissociating conditions, anti-ASGP-2 immunoprecipitated primarily components of Mr = 120,000 and about 400,000 from lysates of cells labeled for 1 h with mannose, glucosamine, and threonine. Under similar conditions, anti-ASGP-1 immunoprecipitated the Mr = 400,000 component and a second major labeled component of about 330,000. Pulse-chase labeling with 35S-labeled amino acids followed by immunoprecipitation with anti-ASGP-2 indicated a precursor-product relationship for the Mr = 400,000 component, designated pSMC-1 (precursor, sialomucin complex), and ASGP-2. Similar pulse-chase analyses of threonine labeled cells using anti-ASGP-1 showed equivalent amounts of immunoprecipitated pSMC-1 and pSMC-2, both of which disappeared with kinetics similar to those observed for pSMC-1 immunoprecipitated with anti-ASGP-2. A precursor-product relationship of both pSMC-1 and pSMC-2 to ASGP-1 was suggested by combined precipitations with anti-ASGP-1 and peanut agglutinin, which precipitates ASGP-1 specifically. Immunoblot and lectin blot analyses indicated that pSMC-1 and pSMC 2 from the immunoprecipitates bind anti-ASGP-2, anti-ASGP-1, and concanavalin A. Moreover, these three components can also be labeled with mannose; the mannose was removed from 30-min pulse-labeled anti-ASGP-2 immunoprecipitates by incubation with endo-beta-N-acetylglucosaminidase H, indicating the presence of only high mannose N-linked oligosaccharides in pSMC-1. One-dimensional peptide maps of 35S-labeled pSMC-1 and Mr = 120,000 ASGP-2 showed several corresponding bands. These results indicate that both ASGP-1 and ASGP-2 can be synthesized from a common high Mr precursor. We propose that complex is formed from pSMC-1 by proteolytic cleavage to yield Mr = 120,000 ASGP-2 plus the precursor to ASGP-1 early in the transit pathway from the endoplasmic reticulum to the cell surface. PMID- 2111321 TI - Protozoan hemoglobin from Tetrahymena pyriformis. Isolation, characterization, and amino acid sequence. AB - A hemoprotein that can be defined as hemoglobin based on oxygen binding was isolated from Tetrahymena pyriformis. The protein exists in monomeric form and is separated into four fractions (Ia, Ib, IIa, and IIb) on a CM-cellulose column. From examinations of the absorption spectra and the N-terminal sequence, fractions Ia and Ib were assigned to the oxy-form and its met-form, respectively, of the one protein, while IIa and IIb corresponded to those of the other one. The complete amino acid sequence was therefore determined of fractions I and II. The I was composed of 121 amino acid residues, with the N-terminal serine being blocked. The II, on the other hand, consisted of 119 amino acid residues, its sequence being exactly identical to that of the third residue, lysine, to the C terminal lysine of the fraction I. Although the genomic multiplicity cannot be ruled out completely, we have concluded that fraction II is a degradation product of the fraction I by endogeneous proteases. The amino acid sequence of T. pyriformis hemoglobin is very unique and showed no notable degree of similarity with the other hemoglobins sequenced so far, but it was found to be 33.9% identical with Paramecium caudatum hemoglobin by a maximal alignment. PMID- 2111322 TI - Structural analysis of human apolipoprotein A-I variants. Amino acid substitutions are nonrandomly distributed throughout the apolipoprotein A-I primary structure. AB - In the course of an electrophoretic mutation screening program of 32,000 dried blood samples from newborns, 17 genetic variants of apolipoprotein A-I (apoA-I) were found and structurally analyzed. The following defects were identified by the combined use of high performance liquid chromatography, time-of-flight secondary ion mass spectrometry, and sequence analysis: Pro3----Arg (1 x), Pro4-- -Arg (1 x), Asp89----Glu (1 x), Lys107----0 (4 x), Lys107----Met (2 x), Glu139--- Gly (2 x), Glu147----Val (1 x), Pro165----Arg (4 x), and Glu198----Lys (1 x). The distribution of point mutations in the apoA-I gene leading to these 9 and 11 other variants of apoA-I reported previously was statistically analyzed. Substitutions are overrepresented in the 10 amino-terminal amino acids (p less than 0.001, chi 2-test) and in residues 103-177 (p less than 0.025, chi 2-test) or residues 103-198 (p less than 0.05, chi 2-test), respectively. We further noted the following. (i) Prolines were substituted by arginine or histidine residues at a frequency much higher than expected on the basis of random nucleotide substitutions (5 out of 18 "electrically non-neutral" amino acid substitutions, p less than 0.001, chi 2-test). These substitutions are the result of transversions of cytosines contained within stretches of at least 5 consecutive cytosines in the apoA-I gene. The observed hypervariability of the apoA-I amino terminus, therefore, might be caused by a hot spot for mutation formed by the 7 subsequent cytosines in codons 3, 4, and 5. (ii) CpG dinucleotides were overrepresentatively affected by C----T transitions (5 out of 18 electrically nonneutral amino acid substitution, p less than 0.001, chi 2 test). The hypervariability of the apoA-I alpha-helical domain might therefore be caused by CpG dinucleotides predominantly occurring in codons 120-208 of apoA-I (82 out of 125). (iii) Comparison of mutation sites in the human apoA-I gene with sites of nonsynonymous substitutions revealed that amino acid substitutions found in human apoA-I were predominantly localized in areas that were little conserved during mammalian evolution. These regions may therefore represent areas of less structural constraint for the function of apoA-I. PMID- 2111323 TI - Involvement of denaturation-like changes in Pseudomonas exotoxin a hydrophobicity and membrane penetration determined by characterization of pH and thermal transitions. Roles of two distinct conformationally altered states. AB - Previous investigators have shown that exotoxin A undergoes a conformational switch to a hydrophobic state at low pH. This change appears to play a role in exotoxin A entry into cells by facilitating its penetration of the membranes of acidic organelles. We have examined the effects of pH, temperature, and denaturants in order to define the role of conformational changes in membrane penetration by the exotoxin. We find that two distinct low pH conformations exist. An intermediate low pH state (LI) dominates at pH 3.7-5.4 and is distinguished by blue-shifted fluorescence and weak or no hydrophobicity. The second low pH state (LII) is dominant below pH 3.7 and is characterized by red shifted fluorescence and strong hydrophobicity. LI is a folded state as judged by its spectroscopic properties and the observation that it undergoes distinct and cooperative thermal and denaturant induced unfolding transitions. LII appears to be more like a denatured state, as it shows no cooperative thermal or denaturant induced transitions and has spectroscopic properties very similar to exotoxin A that has been thermally denatured at pH 7. Exotoxin A in the LII state strongly binds detergent micelles and binds and inserts into model membranes. Therefore, denaturation-like conformational changes appear to play an important role in membrane insertion. The pH of the transition to a membrane-inserting state is influenced by the composition of the model membranes and is close to pH 5 in the presence of vesicles containing a phosphatidylglycerol/phosphatidylcholine mixture. These vesicles probably promote formation of the LII state via mass action effects. The implication of these results for membrane penetration and translocation of proteins without apparent hydrophobic regions, such as exotoxin A, is discussed. PMID- 2111324 TI - Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney. AB - We have purified carbonic anhydrase (CA) IV from human lung membranes to apparent homogeneity in a form which is catalytically active and stable to storage. It has an apparent molecular mass of 35 kDa, is insensitive to endoglycosidases, and seems to contain no N-linked or O-linked oligosaccharide chains. Reduction of disulfide linkages led to altered migration on sodium dodecyl sulfate polyacrylamide gel electrophoresis and loss of catalytic activity. CA IV resembles CA II in being a "high activity" isozyme, relatively resistant to inhibition by halide ions and sensitive to inhibition by sulfonamides. Application of this purification to human kidney membranes produced homogeneous enzyme with nearly identical properties. Amino acid compositions of both lung and kidney CA IV were similar, as were tryptic peptide patterns resolved on high performance liquid chromatography (HPLC). Amino-terminal sequences of native enzyme from lung and kidney were identical, as were amino-terminal sequences of the three major tryptic peptides resolved on reverse phase HPLC. Isoelectric focusing revealed microheterogeneity in enzyme from both sources. Antibody raised to human lung CA IV reacted equally strongly with CA IV from kidney, but very weakly or not at all with other CAs. Treatment of lung membranes and kidney membranes with phosphatidylinositol-specific phospholipase C released over half of the membrane-bound CA IV, suggesting that at least half of the CA IV in both organs is anchored to membranes by phosphatidylinositol-glycan linkages. PMID- 2111325 TI - Sulfated N-linked oligosaccharides affect secretion but are not essential for the transport, proteolytic processing, and sorting of lysosomal enzymes in Dictyostelium discoideum. AB - Although previous studies have indicated that N-linked oligosaccharides on lysosomal enzymes in Dictyostelium discoideum are extensively phosphorylated and sulfated, the role of these modifications in the sorting and function of these enzymes remains to be determined. We have used radiolabel pulse-chase, subcellular fractionation, and immunofluorescence microscopy to analyze the transport, processing, secretion, and sorting of two lysosomal enzymes in a mutant, HL244, which is almost completely defective in sulfation. [3H]Mannose labeled N-linked oligosaccharides were released from immunoprecipitated alpha mannosidase and beta-glucosidase of HL244 by digestion with peptide: N glycosidase. The size, Man9-10GlcNAc2, and processing of the neutral species were similar to that found in the wild type, but the anionic oligosaccharides were less charged than those from the wild-type enzymes. All of the negative charges on the oligosaccharides for HL244 were due to the presence of 1, 2, or 3 phosphodiesters and not to sulfate esters. The rate of proteolytic processing of precursor forms of alpha-mannosidase and beta-glucosidase to mature forms in HL244 was identical to wild type. The precursor polypeptides in the mutant and the wild type were membrane associated until being processed to mature forms; therefore, sulfated sugars are not essential for this association. Furthermore, the rate of transport of alpha-mannosidase and beta-glucosidase from the endoplasmic reticulum to the Golgi complex was normal in the mutant as determined by the rate at which the newly synthesized proteins became resistant to the enzyme, endo-beta-N-acetylglucosaminidase H. There was no increase in the percentage of newly synthesized mutant precursors which escaped sorting and were secreted, and the intracellularly retained lysosomal enzymes were properly localized to lysosomes as determined by fractionation of cell organelles on Percoll gradients and immunofluorescence microscopy. However, the mutant secreted lysosomally localized mature forms of the enzymes at 2-fold lower rates than wild type cells during both growth and during starvation conditions that stimulate secretion. Furthermore, the mutant was more resistant to the effects of chloroquine treatment which results in the missorting and oversecretion of lysosomal enzymes. Together, these results suggest that sulfation of N-linked oligosaccharides is not essential for the transport, processing, or sorting of lysosomal enzymes in D. discoideum, but these modified oligosaccharides may function in the secretion of mature forms of the enzymes from lysosomes. PMID- 2111326 TI - The multisubunit structure of synaptophysin. Relationship between disulfide bonding and homo-oligomerization. AB - Synaptophysin, a major membrane protein of synaptic vesicles, contains four transmembrane regions and two intravesicular loops. Synaptophysin monomers associate into homopolymers that have the potential to form channels in the synaptic vesicle membrane. Here we show that in native synaptophysin, homopolymers are linked by noncovalent forces. The molecule contains unstable intramolecular disulfide bonds that undergo disulfide exchange during solubilization, thereby covalently cross-linking neighboring synaptophysin molecules. The locations of the intramolecular disulfide bonds in synaptophysin were determined, revealing that each of the two intravesicular loops of synaptophysin is circularized by a single disulfide bond. Cross-linking of synaptophysin by disulfide bonds can be triggered in synaptic vesicles and in intact cells by a cycle of reduction and oxidation, suggesting that native synaptophysin is a homomultimer in situ. In addition, chemical cross-linking of native synaptophysin demonstrates that a low molecular weight protein is specifically associated with synaptophysin complexes and is lost upon reduction of the intramolecular disulfide bonds. These data suggest that native synaptophysin forms a noncovalent homomultimeric complex whose structure and interaction with other proteins are dependent on the integrity of its intramolecular disulfide bonds and phospholipid environment. PMID- 2111327 TI - Combined treatment with indomethacin and low-dose heparin after total hip replacement. A double-blind placebo-controlled clinical trial. AB - We studied the safety of combining the postoperative use of a non-steroidal anti inflammatory drug with low-dose heparin. In a double-blind, placebo-controlled clinical trial we reviewed the complications in 235 patients after total hip replacement, all treated with low-dose heparin and either indomethacin or a placebo. The incidence and type of complications in the two groups were nearly equal; indomethacin-treated patients had no increase in complications related to bleeding. Postoperative bleeding into drains was marginally greater in the indomethacin group, although the difference was not statistically significant. We conclude that treatment with indomethacin and low-dose heparin after hip replacement does not significantly increase the bleeding or other complications. We also found that patients receiving indomethacin were mobilised an average of one day before those on placebo. PMID- 2111328 TI - DNA-binding activity of Jun is increased through its interaction with Fos. AB - Transcription factor AP-1 mediates induction of a set of genes in response to the phorbol ester tumor promoter TPA. Recently, AP-1 preparations from HeLa cells were shown to contain a product of the c-JUN protooncogene (Jun/AP-1) which forms a tight complex with the Fos protein. In this paper, we examine the role of the Fos protein in the DNA-binding activity of the AP-1 complex. We show that the DNA binding activity of bacterially expressed trpE-Jun fusion proteins is increased many-fold upon their interaction with Fos (or a Fos-related antigen) expressed from a baculovirus vector. The site of Fos interaction is within the DNA-binding domain of Jun/AP-1, and anti-Fos antibodies interfere with the binding of affinity purified AP-1 to DNA. These results suggest that, by associating with Jun/AP-1, Fos is responsible for the formation of a multimeric protein complex that has greater affinity for the target sequence than does Jun/AP-1 alone. PMID- 2111329 TI - Large-scale purification of factor VIII by affinity chromatography: optimization of process parameters. AB - The optimization of a new process for the extraction of human coagulation factor VIII (FVIII) from plasma with the tailor-made affinity matrix dimethylamino propylcarbamylpentyl-Sepharose CL-4B (C3-C5 matrix) is described. First, plasma is applied to DEAE-Sephadex A-50 anion exchanger in order to separate a number of proteins, including coagulation factors II, IX and X (prothrombin complex), from FVIII. Subsequently, the unbound fraction of the ion exchanger, containing FVIII, is contacted with the C3-C5 affinity matrix. Optimization of the FVIII affinity chromatographic procedure is accomplished in terms of the ligand density of the matrix, adsorption mode (batch-wise versus column-wise adsorption and matrix to plasma ratio), and conditions of pH and conductivity to be applied on washing and desorption. In scale-up experiments, by processing 20 l of plasma, the recovery (340 U VIII:C/kg plasma) and the specific activity (s.a.) (1.2 U VIII:C/mg protein) are better than those obtained by cryoprecipitation (recovery 300 U VIII:C/kg plasma, s.a. 0.3 U VIII:C/mg protein). The newly developed process using the specially designed C3-C5 affinity matrix has potential application in the process-scale purification of FVIII. PMID- 2111330 TI - Measurement of the formation of a thioglucuronide, a metabolite of malotilate, in rat hepatic microsomes by high-performance liquid chromatography. PMID- 2111331 TI - Encainide and metabolites analysis in serum or plasma using a reversed-phase high performance liquid chromatographic technique. PMID- 2111332 TI - High-performance liquid chromatographic method for analysis of 2',3' dideoxyinosine in human body fluids. AB - A paired-ion high-performance liquid chromatographic method was developed to measure concentrations of 2',3'-dideoxyinosine (ddI) in human plasma, urine and cerebrospinal fluid. Samples were prepared using a solid-phase extraction technique which allows for a five-fold concentration of the drug. 2' Deoxyguanosine was added as an internal standard prior to the extraction. Recoveries for 2'-deoxyguanosine and ddI were 80 +/- 15 and 85 +/- 10%, respectively. Extracted samples were then injected onto a C18 column and eluted isocratically with a mobile phase containing 0.1% of the ion-pairing reagent, heptafluorobutyric acid, and 5% acetonitrile. The retention time was 7.4 min for 2'-deoxyguanosine and 8.4 min for ddI. The lower limit of detection for ddI is 0.1 microM. Using this technique the acid lability of ddI was demonstrated and the plasma concentration versus time profile from a patient receiving the drug was examined. PMID- 2111333 TI - Recombinant interferon-gamma applied to the brain ventricular system protects rats against pseudorabies. AB - We examined the prophylactic efficacy of recombinant rat interferon-gamma (IFN gamma) administered directly into the brain ventricular system or via the intraperitoneal (i.p.) route against central and peripheral pseudorabies virus (PRV) infection. Intraperitoneally given IFN-gamma completely protected rats against a lethal i.p. PRV infection. The same regimen showed no protective effect against lethal intracerebroventricular (i.c.v.) PRV challenge even if IFN-gamma was given in high concentrations. When given via the i.c.v. route, IFN-gamma protected rats against lethal i.c.v. infection and also evoked partial protection with extended survival times of i.p. infected rats. Our results demonstrate an IFN-gamma-mediated antiviral effect in the central nervous system. PMID- 2111335 TI - Valproic acid in the treatment of refractory bipolar disorder. PMID- 2111334 TI - Antigen presentation by brain microvessel smooth muscle and endothelium. AB - It has been previously reported that cultured brain microvessel smooth muscle cells (SM) express major histocompatibility complex (MHC) class II antigen. Here we report that SM is able to present ovalbumin (OVA) antigen to an OVA-specific T cell hybridoma (A2.2E10) and also presents keyhole limpet hemocyanin (KLH) to a KLH-specific T cell clone (HDK-1). Both the class II expression and the antigen presenting capacity of SM cells is increased by interferon-gamma stimulation. Antigen presentation by SM is also MHC restricted as it is blocked by anti-Ia monoclonal antibodies. In contrast to SM, brain endothelium (En) presents whole OVA, digested OVA and KLH poorly, to a much lesser degree than SM, to the same antigen-specific T cells. PMID- 2111336 TI - Clinical use of the determination of serotonin in whole blood. AB - Whole blood serotonin (5-hydroxytryptamine, 5-HT) was assayed, and factors possibly influencing 5-HT content were investigated in healthy controls. No significant circadian rhythm or effect of dexamethasone or meals was observed. After use of fluvoxamine, a specific 5-HT reuptake inhibitor, the whole-blood 5 HT concentration of patients was strongly reduced. After treatment with tranylcypromine, an unspecific monoamine oxidase inhibitor (MAOI), the 5-HT content was increased. Determination of whole blood 5-HT in patients treated with fluvoxamine presents a measure of drug compliance. Furthermore, the method may have clinical potential for finding an adequate dose when a 5-HT reuptake inhibitor or an MAOI is used. PMID- 2111337 TI - Compartmental and topographical specificity of reinnervation of the glutaeus muscle in the adult toad (Bufo marinus). AB - The extent to which the compartmental and topographical innervation patterns were re-established in the mature glutaeus muscle after nerve cut was determined by HRP retrograde labelling procedures and single motor unit glycogen depletion experiments. Glutaeus muscle axons normally cluster together along the length of the sciatic nerve and enter the triceps femoris nerve along with axons to the cruralis and tensor fasciae latae muscles. Glutaeus axons did not specifically reinnervate the glutaeus muscle after cutting the triceps femoris nerve. Axons within the glutaeus muscle nerve are grouped according to the primary nerve branch, and therefore muscle compartment, for which they are destined. When the glutaeus nerve was cut, regenerating axons lost their compartmental organization within the glutaeus nerve and nonspecifically reinnervated both glutaeus muscle compartments. In marked contrast, the topographical projection of spinal motoneurones to the ventral and dorsal halves of the glutaeus muscle was largely re-established after glutaeus nerve cut; that is, rostral motoneurones mostly reinnervated ventral muscle fibres, whereas caudal motoneurones reinnervated dorsally located muscle fibres. The relatively confined caudal projection was closely related to the sharp fibre type divisions within the glutaeus muscle. The results suggest that factor(s) present during development that determine the correct innervation of a muscle and its compartments no longer operate in the adult, although cues that direct motor terminals to their appropriate muscle region do, and these are most likely related to the topographical distribution of fibre types. PMID- 2111338 TI - Immunolocalization and quantitation of a novel nerve terminal protein in spinal cord development. AB - In the adult spinal cord, the neuron-specific protein NT75 is located in nerve terminals synapsing in the superficial laminae of the dorsal horn. The present study examines the occurrence of NT75 in the developing rat spinal cord. NT75 immunoreactivity is detectable in primary afferent axons at the dorsal root entry zone on embryonic day 15. Subsequently, staining of presumptive nerve terminals appears in the deeper laminae of the dorsal horn, expanding into the superficial laminae during the first postnatal week. NT75 staining also appears in developing corticospinal tract axons in the brainstem at birth, and at lumbosacral levels by postnatal day 5. As NT75-positive nerve terminals approach the adult distribution, staining of primary afferent and corticospinal axons decreases, becoming undetectable by postnatal day 30. Dense transient staining of presumed nerve terminals in the ventral horn is also apparent during early postnatal development. Quantitative analysis of developing spinal cord shows a low level of NT75 immunoreactivity at birth. NT75 activity then increases substantially, reaching values by the third and fourth postnatal weeks up to 2.5 times that seen in adults. The occurrence of NT75 immunoreactivity correlates with the reported time course of synaptic development in the spinal cord. In addition, the results suggest that NT75 immunoreactivity is maintained at high levels in the nerve terminals of certain neural pathways into adulthood, whereas in other systems NT75 immunoreactivity may be detectable only during development. PMID- 2111339 TI - Effect of fertirelin acetate or buserelin on conception rate at first or second insemination in lactating dairy cows. AB - The objective of this study was to determine if fertirelin acetate and buserelin, two GnRH agonists, improve conception rate when administered at the time of first or second AI in lactating dairy cows. The study consisted of a common protocol conducted at 10 commercial dairy farms. Approximately 150 cows within each dairy were assigned randomly in replicates to receive intramuscularly either no injection or injection of 25, 50, 75, or 100 micrograms fertirelin acetate or 10 micrograms buserelin immediately after AI. Cows were subjected to the reproductive management practices normal for each location. Cows at each location were palpated for pregnancy status at 35 to 60 d postinjection. No improvement in conception rate was detected in response to either agonist (control = 48%, fertirelin acetate = 41.5%, buserelin = 39.7%). Conception rate was unaffected by either days postpartum at injection or overall fertility of the individual herds. These observations do not support the routine use of doses of 25 to 100 micrograms fertirelin acetate or 10 micrograms buserelin at the time of first or second AI as a means to improve conception rate in lactating dairy cows. PMID- 2111340 TI - Effects of dietary protein degradability and casein or amino acid infusions on production and plasma amino acids in dairy cows. AB - Responses to daily abomasal infusions of 400 g sodium caseinate, 400 g hydrolyzed casein, or 11.3 g L-methionine plus 30.1 g L-lysine were compared in eight Holstein cows fed diets with estimated ruminal protein degradabilities of 70 and 60.%. Basal diets contained corn silage and corn with either soybean meal or 66.7:33.3 soybean meal:corn gluten meal added. Infusion with Methionine plus lysine increased milk protein content when cows fed either diet but increased milk fat content and yield only when the soybean meal diet was fed. Sodium caseinate increased milk and milk protein production and decreased milk fat percentage. Concentration of total essential amino acids, branched chain amino acids, and urea cycle amino acids were increased by the infusion of both casein sources. Methionine-lysine infusion increased plasma lysine and taurine, a metabolite of methionine, suggesting that absorbed methionine was extensively metabolized. Results demonstrate an impact of both ruminal degradability of dietary protein and form of infused protein on amino acid nutrition of lactating daily cows. PMID- 2111341 TI - Cytotoxic activity and lymphokine production of T cell receptor (TCR)-alpha beta+ and TCR-gamma delta+ cytotoxic T lymphocyte (CTL) clones recognizing HLA-A2 and HLA-A2 mutants. Recognition of TCR-gamma delta+ CTL clones is affected by mutations at positions 152 and 156. AB - TCR-gamma delta+ CTL clones were generated from CD4-CD8- T cells that were stimulated twice with the cell line JY. Either IL-2 or IL-4 was used as growth factor. A number of TCR-gamma delta+ clones were found to lyse the stimulator cell line JY. Two of these clones secreted N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester serine esterase activity after stimulation with JY cells. The cytotoxic activity of these two clones was blocked by a mAb specific for HLA-A2. Moreover, these two TCR-gamma delta+ clones selectively lysed human fibroblast line M1 and murine P815 cells transfected with DNA fragments encoding HLA-A2 but not those transfected with HLA-B7 encoding DNA, indicating that these clones recognize HLA-A2. Analysis of the recognition of HLA-A2 by using target cells transfected with mutated HLA-A2 encoding genes revealed that the nature of the amino acid at position 152 of the molecule is critical for recognition of the TCR alpha beta+ as well as the TCR-gamma delta+ CTL clones since replacement of Val for Ala at that position resulted in abrogation of recognition of one TCR-gamma delta+ and one TCR-alpha beta+ clone and substitution of Val for Glu affected recognition of all clones. Substitution of Leu for Trp at position 156 abrogated recognition by one TCR-gamma delta+ and one TCR-alpha beta+ T cell clone, but recognition by the other clones was not changed. All clones were able to secrete IL-2, IFN-gamma, and GM-CSF but not IL-4 after activation. PMID- 2111342 TI - Identification of a single non-H-2 gene regulating graft-versus-host disease response. AB - Non-MHC loci have been shown to play an important role in the development and regulation of graft-vs-host disease (GVHD). In the murine model of GVHD under study, injection of C57BL/6 spleen cells into unirradiated (C57BL/6 x DBA/2)F1 hybrid recipient mice results in an acute form of GVHD characterized by CTL, suppressor cells, and runting. In contrast, injection of DBA/2 spleen cells into the same recipients results in a chronic form of GVHD that is characterized by a lack of CTL and hyperproduction of Ig and autoantibodies. After preliminary studies with the use of congenic mice showed that non-MHC loci were controlling GVHD responses in this model, genetic analysis of GVHD response of BXD recombinant inbred strains and (B10.D2 x DBA/2) X DBA/2 BC mice identified a single locus, Gvh, on chromosome 7 that controls whether acute or chronic GVHD results from injection of parental lymphocytes into unirradiated (C57BL/6 x DBA/2)F1 recipient mice. PMID- 2111343 TI - Regulation of arachidonic acid release in mouse peritoneal macrophages. The role of extracellular calcium and protein kinase C. AB - Primary cultures of [3H]arachidonic acid-prelabeled mouse peritoneal macrophages were stimulated with the physiologic agonists zymosan and Con A. The cells released a large quantity of labeled compounds into the extracellular medium. When the cells were preincubated for 10 min with PMA at concentrations from 10 to 1000 ng/ml, zymosan- and Con A-stimulated compound release was greatly enhanced. PMA also potentiated arachidonic acid release when cells were stimulated with the calcium ionophore A23187. However, under the same conditions, PMA treatment blocked agonist- and ionophore-mediated phosphoinositide hydrolysis in cells prelabeled with [3H]inositol. Thus, PMA treatment appears to have dissociated agonist-induced arachidonic acid liberation (index of phospholipase A2) from phosphoinositide hydrolysis (index of phospholipase C), suggesting that these two coupling processes can occur in a parallel and independent manner in mouse peritoneal macrophages. Furthermore, the ligand-induced arachidonic acid release from PMA-treated macrophages was shown to be directly dependent on the extracellular calcium concentration. Considering that in PMA-pretreated cells, receptor-mediated phosphoinositide breakdown and intracellular calcium mobilization were abolished, our data suggest that the extracellular calcium influx that takes place after receptor-ligand interaction may be a required event for arachidonic acid mobilization in mouse peritoneal macrophages. PMID- 2111344 TI - Activation of mouse peritoneal macrophages during infection with Salmonella typhimurium does not result in enhanced intracellular killing. AB - Our study was performed to investigate whether macrophages become activated during an infection with Salmonella typhimurium and, if so, whether these activated macrophages kill S. typhimurium faster than resident macrophages. Mice received i.v. injections with a sublethal number of S. typhimurium; on about day 12 of the infection the numbers of bacteria in the liver and the spleen were maximal. During the infection, activation of peritoneal macrophages could be demonstrated on the basis of three criteria, i.e., the ability to inhibit the proliferation of Toxoplasma gondii, an enhanced production of H2O2 and an increased expression of Ia Ag. The rate of in vitro intracellular killing of S. typhimurium by these activated macrophages was not increased compared to that for resident macrophages. To determine the growth of S. typhimurium in activated mice a nalidixic acid-resistant mutant strain, called S. typhimurium 510R, was used. The net growth rates of the mutant S. typhimurium 510R in the spleen of S. typhimurium 510-activated and normal mice were similar. However, in the liver of S. typhimurium 510-activated mice the number of S. typhimurium 510R did not change during 3 to 48 h after injection. The role of specific antibodies during the initial phase of the infection was negligible, because only low levels of antibodies were detected during the first 15 days of infection and the growth rates of S. typhimurium 510 in the spleen and liver of mice with high titers of antibodies were not significantly different from the rates in normal mice. The results of this study demonstrate that although macrophages become activated during an infection with S. typhimurium, these cells do not display an enhanced bactericidal activity in vitro and in vivo no significant effect on the growth rate of S. typhimurium in the spleen and a bacteriostatic effect in the liver is found. Hence macrophage activation is probably not very important in the host defense against S. typhimurium. PMID- 2111345 TI - Monoclonal antibodies against Trypanosoma cruzi neuraminidase reveal enzyme polymorphism, recognize a subset of trypomastigotes, and enhance infection in vitro. AB - The identification and characterization of two murine mAb (TCN-1 and TCN-2) that react with the neuraminidase of Trypanosoma cruzi is reported. The mAb were identified based on their ability to inhibit enzyme activity and recognize neuraminidase in crude enzyme preparations. TCN-1 and TCN-2 recognized Ag in tissue culture trypomastigotes but not in the amastigotes, epimastigotes, or metacyclic trypomastigotes using immunoblot assays and immunofluorescence. In addition, clones Y-H6, MV-13, and Silvio X-10/4 of T. cruzi revealed a unique banding pattern characteristic of each clone. In Silvio X-10/4, the mAb recognized four distinct bands ranging from 121,000 to 203,000 whereas in Y-H6 and MV-13 they identified bands ranging from 138,000 to 222,000. Characterization of neuraminidase by two-dimensional PAGE revealed the polypeptides that make up the enzyme to have isoelectrical points ranging from 6.55 to 7.30. Immunofluorescence and C-mediated lysis assays showed that the mAb reacted with a subset of trypomastigotes representing 28% of the total parasite population. Functional studies showed that the mAb enhanced infection of cultured cells by trypomastigotes. Our experiments confirm previous findings with polyclonal Ab and are in accordance with the hypothesis that neuraminidase modulates infection through a negative control mechanism. PMID- 2111346 TI - The IFN-gamma response of the murine invariant chain gene is mediated by a complex enhancer that includes several MHC class II consensus elements. AB - IFN-gamma induces the expression of the MHC class II-associated invariant chain (IN) protein in a variety of cells of nonlymphoid origin. Here we analyze the transcription from the murine invariant chain gene and delimit the cis-acting sequences which confer IFN-gamma responsiveness in human fibroblasts. The major start of transcription of the gene is located 29 bp 3' of a TATA box and 85 bp 5' of the single ATG codon which opens the reading frame. To identify the regulatory elements of the murine IN promoter which respond to IFN-gamma, the 5' flanking region of the gene including its capsite and 85 bp of coding region have been cloned in front of the bacterial chloramphenicol acetyl transferase (CAT) gene. Examination of this construct and various 5' and 3' deletion mutants for IFN gamma inducibility in transient transfection assays revealed that DNA sequences between -261 and -189 were essential and sufficient for the induction. Removal of sequences between -215 and -189 reduced inducibility of the IN-promoter and abolished the capacity of the element to transmit inducibility to a heterologous promoter. Single or multiple base changes in other parts of the element also abolished inducibility. Cotransfection of a 350 molar excess of the IFN-gamma response element with an inducible IN-CAT chimeric construct blocked inducibility, suggesting positive regulation. A protein binding to the central part of the IFN-gamma response element was detectable in gel retardation experiments; it was active only in extracts from IFN-gamma-treated cells. PMID- 2111347 TI - Structural characterization of H chain-associated idiotopes of anti-p azophenylarsonate monoclonal antibodies. AB - The majority of antibodies directed against p-azophenylarsonate (Ars) protein conjugates elicited during secondary immune responses of A/J mice bear a heritable cross-reactive Id (CRIa or IdCR) which corresponds to the utilization of a unique combination of variable region gene segments that can differ by somatic mutations. One such monoclonal anti-Ars antibody, 44-10, bears IdCR as defined by rabbit antisera but does not react with two anti-idiotypic mAb, 5Ci and AD8, which react with all primary (unmutated) IdCR+ antibodies and some secondary response IdCR+ antibodies. We therefore determined the complete sequence of antibody 44-10, which differs from the germline encoded (unmutated) IdCR+ antibody 36-65 at four positions in the H chain V region (VH): position 55 in the second complementarity determining region, 100 and 107 (D-gene junctions) and 110 (in JH2). The 44-10 L chain is unmutated. Sequence analyses of five other secondary immune response anti-Ars IdCR+ antibodies chosen on the basis of sharing one or more of the amino acid substitutions found in 44-10, were correlated with idiotypic expression of this set of antibodies. The results suggest that the mutation at VH position 55 (Asn----Lys) is responsible for loss of the 5Ci idiotope. To substantiate this hypothesis, oligonucleotide-directed mutagenesis of the germline encoded (unmutated) IdCR+ antibody was used to produce two mutants, one with VH Lys 55 and the other containing residues at positions 100, 107 and 110 identical to those found in 44-10. Id binding studies on these mutants confirm that 5Ci idiotope loss is due to conformational changes resulting from a mutation at VH position 55. This mutation also results in loss of the AD8 idiotope in the structural context of antibody 44-10. PMID- 2111348 TI - Northern hybridization analysis of VH gene expression in murine monoclonal antibodies directed to cancer-associated ganglioside antigens having various sialic acid linkages. AB - The expression of the VH genes in 46 murine hybridoma cells that secrete mAb directed to the cancer-associated carbohydrate Ag, especially acidic glycolipids such as gangliosides and sulfated glycoplipids, was analyzed by Northern hybridization of poly(A)+ RNA of hybridoma with cDNA probes for nine VH gene families. Different hybridomas tended to express VH genes of the same family when the cognate Ag had the same or similar carbohydrate structures; i.e., the VH genes of the J558 family (group 1) were preferentially expressed in the mAb directed to various gangliosides that have NeuAc alpha (or NeuGc alpha) 2-3 and/or 2-8 linkage (71%), the most common linkage of sialic acid residues in the gangliosides of higher animals, and the hybridomas directed to sulfated glycolipids also expressed mainly the VH genes of the J558 family (80%). In contrast, the five mAb directed to various gangliosides with NeuAc alpha 2-6 linkage were exclusively encoded by the VH genes of Q52 family (group 2, 100%), and three antibodies directed to gangliosides with a NeuAc alpha 2-9 linkage all expressed genes of J606 family (group 6, 100%). The VH family usage was largely correlated with the linkage of sialic acid residues in the cognate carbohydrate Ag, but was not correlated at all with the difference in the fine specificities toward the core neutral carbohydrate chain, to which the sialic acid residues were attached. These findings suggest that the VH gene family in these anticarbohydrate antibodies is selected, depending primarily on the linkage of the sialic acid residues in carbohydrate Ag; these residues form the immunodominant sugar residue in the respective antigenic determinant. PMID- 2111349 TI - Induction of antibody-dependent cellular cytotoxicity in vivo by IFN-alpha and its antitumor efficacy against established B16 melanoma liver metastases when combined with specific anti-B16 monoclonal antibody. AB - We have previously shown the ability of different cytokines to induce antibody dependent cellular cytotoxicity (ADCC) in murine cells in vitro. In addition we found that the administration to mice of IL-2-induced cells which mediated ADCC and that these cells were phenotypically similar to the cells induced in vitro. In the present study we tested the ability of various cytokines, including IL-1, TNF, IFN-alpha, and IFN-gamma to induce ADCC in vivo. We found that both IFN alpha and IFN-gamma induced ADCC in the livers and spleens of C3H/Hen-treated mice and that these cytokines together with TNF enhanced the IL-2-induced ADCC in vivo. In C57BL/6 mice which, as previously shown, exhibit relatively low ADCC activity, IFN-alpha and IFN-gamma increased the IL-2-induced ADCC only when 100,000 U of IL-2 were used for priming. The effect of IFN-alpha on ADCC was dose dependent and was optimal after the administration of 200,000 U of the cytokine given three times a day for 3 days. Similar to the cells induced in vivo by IL-2, the precursors of the cells mediating ADCC were asialo GM1+ whereas the effectors were mainly nonadherent, Thy-1+ cells. IFN-alpha-generated cells mediating ADCC in the liver and spleen and, when combined with IL-2, ADCC was induced in the thymus as well. This effect of IFN-alpha on the induction of ADCC was exploited in an immunotherapy model in which we found that IFN-alpha significantly enhanced the antibody-mediated antitumor effect on established B16 melanoma liver micrometastases. Furthermore, when IL-2 and IFN-alpha administration was combined with the administration of mAb, a significantly reduced number of established 6- to 8-day B16 melanoma liver macrometastases and prolonged survival of tumor bearing mice were seen. These studies imply that the administration of appropriate cytokine combinations may be a useful adjunct to the administration of mAb for the treatment of cancer in humans. PMID- 2111350 TI - Poly I:C activated macrophages are tumoricidal for TNF-alpha-resistant 3LL tumor cells. AB - Successive coculture of Lewis lung carcinoma (3LL) cells with T cell-derived lymphokines and LPS-activated macrophages has led to the acquisition of 3LL tumor variants (macrophage-resistant 3LL tumor variants (3LL-R)), manifesting a highly reduced sensitivity to the cytotoxic potential of T cell-derived lymphokines and LPS-activated macrophages and TNF-alpha. However, when 3LL-R cells are cocultured with Poly I:C-activated macrophages or with conditioned medium derived from these effector cells a significant lysis is observed. TNF-alpha participates in the cytolytic process of Poly I:C-activated macrophages as anti-TNF-alpha antibodies abolish the cytotoxic effect of these effector cells. In addition, class I IFN is involved because IFN-alpha and IFN-beta act synergistically on TNF-alpha mediated lysis of 3LL-R cells within 18 h. Moreover, anticlass I IFN antibodies abolish the cytolytic capacity of Poly I:C-activated macrophages. Hence, Poly I:C-induced macrophage-mediated cytolysis of 3LL-R cells may result from 1) the induction of macrophages by Poly I:C to secrete high amounts of TNF-alpha and class I IFN and 2) a synergism between IFN-alpha/IFN-beta and TNF-alpha on lysis of 3LL-R cells. This synergism does not result from a class I IFN-mediated enhancement of TNF alpha receptor expression on 3LL-R cells. Therefore, the sensitivity of 3LL-R cells to TNF-alpha-mediated lysis in the presence of class I IFN is most probably regulated at the post-TNF-alpha receptor level. Furthermore, treatment of mice with Poly I:C strongly reduces the metastatic capacity of 3LL-R tumor cells, suggesting the participation of macrophages in the eradication of the established metastasis. Hence, TNF-alpha-resistant 3LL-R tumor cells may serve as a useful tool for the detection of alternative macrophage-related cytotoxins leading to the destruction of neoplastic cells both in vitro and in vivo. PMID- 2111351 TI - Human listeriosis in Scotland 1967-1988. AB - In order to study the epidemiology of listeriosis from 1967-1988 in Scotland, various sources of data were examined. These included reports by laboratories, reference laboratory records, hospital death and discharge records, death certificates and hospital laboratory records. Cases were reported from 13 of Scotland's 15 Health Boards. Case ascertainment via laboratory reports to the Communicable Diseases (Scotland) Unit was validated in two Health Boards. A total of 198 cases was identified with an overall attack rate which increased from 0.5 per million in 1967-1971 to 7.0 per million in 1987-1988. Feto-maternal cases were the commonest (64%). Of all cases, 33% were neonates; 53% presented with bacteraemia and 41% with meningitis. The predominant serovar of Listeria monocytogenes was 4b. PMID- 2111352 TI - Characterization of the synergistic antiproliferative effects of interferon-gamma and tumor necrosis factor on human colon carcinoma cell lines. AB - We employed a tumor-type-specific tissue culture model utilizing three human colon carcinoma cell lines to (i) assess the effects of schedule, sequence, dose, and duration of exposure on the antiproliferative activity of combinations of tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) and to (ii) determine the effects of this combination on the production of a TNF-inducible protein, IFN-beta 2, and an IFN-inducible protein, p78. A statistical model was developed to ascertain the effects of each of three of the variables (sequence, dose, and duration) on the other two. With minor exceptions, the maximal antiproliferative effect in all three cell lines was observed when IFN-gamma and TNF were administered simultaneously, regardless of the doses of each agent and duration of exposure. Exposing the cells to TNF before IFN-gamma resulted in the least inhibition in cell growth. In all three cell lines, the antiproliferative effects of each treatment group were related directly to the duration of exposure. In two of the three cell lines, an intermittent schedule was as effective as a 24-h exposure. No p78 induction was observed in the HCT 116 cell line with IFN-gamma alone, TNF alone, or the combination; p78 was slightly induced in the SKC01 and VACO 9P cell lines with IFN-gamma alone, and was synergistically induced by the combination of TNF and IFN-gamma. Treatment with a neutralizing antibody to IFN-beta did not reverse the antiproliferative effect of any of the three treatment groups in HCT 116 cells. We conclude that the maximum antiproliferative effect in human colon carcinoma can be achieved by the prolonged simultaneous administration of high concentrations of each drug. If clinical toxicity prohibits this schedule, an intermittent schedule of administration may be effective. The mechanism of the synergistic effect is not due to the induction of IFN-beta or the p78 protein. PMID- 2111353 TI - Antiviral and antiproliferative properties of liposome-associated human interferon-gamma. AB - Recombinant human interferon-gamma (rHuIFN-gamma) was associated with liposomes in an attempt to improve its therapeutic efficiency. It was associated with liposomes composed of phosphatidylserine (PS) and phosphatidylcholine (PC) at a ratio of 3:7, and of PS:PC and cholesterol (CHOL) at a ratio of 1:4:5 with efficiencies of 13% and 21%, respectively. The lipid composition influenced the antiviral activity of the liposome-complexed IFN-gamma tested against vesicular stomatitis virus. IFN associated with PS:PC liposomes was fully bioavailable and degraded by trypsin treatment. In contrast, PS:PC:CHOL-IFN was resistant to trypsin, and appeared latent as its full biological activity was seen only after disruption of the liposomes with detergent. Four human tumor cell lines were exposed to free and liposome-associated IFN-gamma. The growth of three solid tumor lines (colon, bladder, and lung) was inhibited by similar concentrations of free IFN and PS:PC-IFN. In contrast, less PS:PC-IFN than free IFN was needed to inhibit histiocytic lymphoma cells. Higher concentrations of PS:PC:CHOL-IFN than of free IFN were needed to inhibit growth of all four cell lines. The specificity of these effects of liposome-associated IFN-gamma were shown by their partial or complete neutralization by antibody to IFN-gamma. When liposome-IFN complexes of either type were stored at 4 degrees C, 30% of the IFN activity remained after 7 days; thereafter, decay was minimal over the next 3 weeks. These data show the formation of stable HuIFN-gamma-liposomes and indicate that the lipid components of these complexes influence their antiviral and antiproliferative activity for several different cell types. PMID- 2111354 TI - A sensitive two-site enzyme immunoassay for the detection of rat interferon-gamma in biological fluids. AB - Two noncompeting monoclonal antibodies (mAbs) directed to rat interferon-gamma (IFN-gamma) were used in a sensitive two-site enzyme-linked immunosorbent assay (ELISA). This permitted quantitation of rat IFN-gamma in culture medium, and serum and was quicker and more sensitive than the conventional antiviral bioassay. A standard curve was linear between 0.1 (15 pg) and 10 (1,500 pg) U/ml. There was no reaction with rat IFN-alpha or -beta or human IFN-gamma, but mouse IFN-gamma was detected with a lower limit of sensitivity of 300 U/ml. Complement dependent inactivation of rat IFN-gamma reduced the sensitivity of the ELISA approximately seven-fold but this could be overcome by adding ethylenediamine tetraacetic acid (EDTA, 10 mM) or other anticomplementary substances to the serum samples. IFN-gamma activity determined by ELISA and bioassay decreased in parallel upon heat denaturation and pH 2.5 treatment, but proteases caused a relatively greater reduction in biological activity. PMID- 2111355 TI - Immunomodulation by recombinant rat interferon-gamma in vivo. AB - Most studies on the immunomodulating effects of interferon-gamma (IFN-gamma) have been performed in vitro, using recombinant mouse and human IFN-gamma preparations. Recently, recombinant rat IFN-gamma (rRIFN-gamma) became available, enabling extensive studies with this new preparation in vivo. In the present study a LEW rat model was used to determine the efficacy of rRIFN-gamma on immune functions in vivo. LEW rats were treated with rRIFN-gamma by continuous intravenous infusion at a dosage of 1.5 x 10(5) U/kg.h for 2 consecutive days. Twelve hours after cessation of rRIFN-gamma administration immune functions, including NK-cell activity, phagocytosis, and mitogen-induced blastogenesis, were assessed. All experimental animals displayed a marked reduction in the number of peripheral blood and bone marrow cells when compared with controls (p less than 0.005). Assessment of immune functions revealed a significant enhancement of NK cell activity (p less than 0.001), phagocytosis (p less than 0.05), and mitogen induced blastogenesis (p less than 0.05). These findings indicate that rRIFN gamma, when given in high dosages, has a stimulatory effect on various immune functions, which substantiates its important immunological role in vivo. PMID- 2111356 TI - Protective activity of recombinant murine tumor necrosis factor-alpha and interferon-gamma against experimental murine lung carcinoma metastases. AB - A variety of biologic and synthetic agents protect BALB/c mice against experimental M109 micrometastases. We have presented evidence that eradication of these metastases is mediated by the activation of host macrophages to the tumoricidal state. We now present evidence that injection of H22, a neutralizing hamster IgG monoclonal antibody to murine interferon-gamma (IFN-gamma; macrophage activating factor), 2 days prior to i.v. tumor inoculation markedly increases the metastatic capacity of M109 lung carcinoma cells. Therefore, we tested several cytokines that induce or mediate macrophage-mediated cytotoxicity, including IFN gamma, tumor necrosis factor-alpha, and interleukin-1 beta (IL-1 beta), for their ability to inhibit the development of experimental M109 lung metastases. Intraperitoneal treatment with recombinant murine (rMu) IFN-gamma (greater than or equal to 10,000 units/mouse) or recombinant murine TNF-alpha (greater than or equal to 10,000 units/mouse) produced greater than 60% inhibition of metastasis formation. Optimal therapy was observed when cytokines were administered 2 days prior to i.v. tumor cell inoculation. Neither IFN-gamma nor TNF-alpha inhibited colony formation of M109 cells in vitro, suggesting a host-mediated mechanism for antitumor activity. Peritoneal macrophages were primed for tumor cytotoxicity by treatment with either IFN-gamma or TNF-alpha. Intraperitoneal treatment with recombinant human IL-1 beta (1 X 10(5) units) lacked antimetastatic activity. The results further support the role of activated macrophages in the destruction of M109 micrometastases. PMID- 2111357 TI - Long-term airway space changes after mandibular setback using bilateral sagittal split osteotomy. AB - Eleven patients were evaluated retrospectively for their long-term changes in hypopharyngeal airway space after surgical correction of mandibular hyperplasia. All patients had undergone mandibular setbacks by way of bilateral sagittal split osteotomies using rigid fixation. The cephalometric evaluation of hypopharyngeal airway space was based on stable craniofacial landmarks. The results of this study indicate that mandibular setback procedures create relative narrowing of the hypopharyngeal airway space, as seen on lateral cephalometric radiographs, which in isolated cases might contribute to the development of an obstructive sleep apnea syndrome. The 2-dimensional evaluation of hypopharyngeal airway space and the clinical implications of the results are discussed. PMID- 2111358 TI - Alveolar soft-part sarcoma of the tongue. Report of a case. AB - A case of alveolar soft-part sarcoma (ASPS) of the tongue in a 19-year-old boy is presented. He underwent a hemiglossectomy and received chemotherapy and has been free of disease for 3 years. The origin of intracytoplasmic periodic acid Shiff(PAS)-positive crystals found in the tumor and the histogenesis of ASPS are briefly discussed. PMID- 2111359 TI - Cephradine (Velosef) penetration of mandibular bone. AB - The concentration of cephradine in serum and mandibular bone was assayed in 28 patients undergoing 3rd molar surgery following a single 1 g intravenous injection. Serum and cortical bone samples taken simultaneously, contained mean cephradine concentrations of 42.11 micrograms/ml and 2.61 micrograms/g respectively. These results, when compared with those reported for other bony sites including the femoral head and knee, show a reduced bone penetration with a bone-to-serum ratio of approximately 0.06:1. PMID- 2111360 TI - Histopathological and scintigraphic features of condylar hyperplasia. AB - This investigation was undertaken to correlate the scintigraphic and histological features of condylar hyperplasia to identify consistent diagnostic findings. A series of 34 surgically excised condyles were examined from a 5 year period. Of these, 20 were diagnosed clinically and histologically as condylar hyperplasia. In 18 of these the presentation was one of increasing facial asymmetry. In all 20 cases there was an increased uptake of Technetium 99 as determined by gamma scintigraphy. The thickness of the fibrous articular layer, undifferentiated germinal mesenchyme layer and the hyperplastic cartilage layer were measured using an eyepiece graticule and the presence and frequency of islands of cartilage in the subchondral bone were noted. 7 patients received tetracycline hydrochloride 14 and 4 days pre-operatively in an attempt to quantify the calcification rate. An uninterrupted layer of undifferentiated germinal mesenchyme is a consistent feature of condylar hyperplasia. An increased uptake on scintigraphy is proportionally related to the thickness of the hypertrophic cartilage and not only to the presence but also the frequency of cartilage islands in the subchondral bone. PMID- 2111361 TI - Marked gingival hyperplasia induced by nifedipine. PMID- 2111362 TI - Intraosseous salivary gland tissue of the mandible mimicking a periapical lesion. AB - A case of an unusual site of salivary gland tissue is presented. The lesion appeared as a radiolucency between the apices of the lateral incisor and canine in a 57-year-old male patient and simulated a periapical lesion. The canine was found vital. PMID- 2111363 TI - Effect of intermaxillary fixation on pulmonary function. AB - A study to measure the pulmonary effects of intermaxillary fixation (IMF) demonstrated that this technique produces a significant degree of airway obstruction. This may be dangerous to patients with limited respiratory reserve due to chronic obstructive airways disease. The impairment of pulmonary function can be assessed pre-operatively and should be estimated in high risk patients. Alternative management of stabilization of jaw fractures that avoid IMF should be considered in such patients. PMID- 2111364 TI - Fracture of the articular eminence. Report of a case. AB - A case of compound fracture of the articular eminence is presented. The injury was sustained as a result of direct trauma which also caused a mandibular symphyseal fracture. Management comprised repositioning and support of the fractured fragment by means of sutures and the application of intermaxillary fixation. There was no long-term limitation of mandibular movement nor was there neurological or hearing deficit as a result of either injury or treatment. PMID- 2111365 TI - Syndromology: an updated conceptual overview. IX. Facial dysmorphology. AB - The role of minor anomalies in dysmorphology is discussed followed by consideration of facial measurements. Photographic documentation, facial change with time, and facial gestalt are emphasized in the process of syndrome diagnosis. Finally, several recent techniques for craniofacial evaluation are presented including facial anthropometry, cephalometrics, laser scanning, three dimensional craniofacial surface imaging from CT scans, and magnetic resonance imaging. PMID- 2111366 TI - Syndromology: an updated conceptual overview. X. References. AB - Part X is the reference section for Parts I through VIII which appeared in the four previous issues of the journal and Part IX which appears in this issue. The reference section itself is divided into two parts. The first part provides general references of selected topics for the interested reader. The second part consists of an alphabetical listing of all references cited in Parts I through IX. PMID- 2111367 TI - Late management of secondarily grafted clefts. AB - 34 patients (40 sides) received alveolo-palatal bone grafts for closure of the residual cleft, thus guiding a lateral incisor or canine into the arch. Long-term follow-up shows that in 41% of the patients uninterrupted arches were achieved with a normal relationship by orthodontic treatment only. 38% needed segmental osteotomies to eliminate the edentulous space, and in only 20% were bridges made to restore the dental arch. 9 (25%) patients still required a Le Fort I advancement osteotomy, despite optimal orthodontic treatment. The use of segmental osteotomies for eliminating edentulous spaces in cleft palate patients is discussed, and their advantage in relation to nasal base support is emphasized. It should be the aim to achieve in every cleft palate patient a complete archform without the need for bridges or removable prostheses. A rational orthodontic-surgical approach to the cleft, lip and palate patient is suggested with respect to naso-maxillary growth and development. PMID- 2111368 TI - Interaction of LDL with human arterial proteoglycans stimulates its uptake by human monocyte-derived macrophages. AB - The aim of this work was to investigate the possible mechanisms for uptake by human monocyte-derived macrophages (HMDM) of low density lipoprotein (LDL) pretreated with human arterial chondroitin-6-SO4-rich proteoglycan (LDL-PG). HMDM were incubated with 125I-labeled tyramine cellobiose-labeled LDL-PG, native LDL, and acetylated LDL (Ac-LDL). The results showed that two to four times more LDL PG than LDL was bound and internalized by the HMDM. Competition experiments showed that LDL-PG competed with native LDL for the apoB,E (LDL) receptor, but not for the Ac-LDL scavenger receptor. Both the LDL and LDL-PG uptake were reduced after preincubation of the macrophages with unlabeled native LDL, though to a lesser extent with LDL-PG. The specific binding of 125I-labeled LDL and 125I labeled LDL-PG at 4 degrees C was both saturable and concentration-dependent. The dissociation constant (Kd) for binding was 8.6 x 10(-9) M for LDL and 9.4 x 10( 9) M for LDL-PG, but the maximum binding (Bmax) was 1.5-times higher for LDL-PG. Cholesterol derived from LDL-PG was less effective than native LDL in suppressing HMG-CoA reductase activity. The results indicate that the uptake of LDL-PG is mediated not only by the LDL-receptor, but also by another unspecific pathway, which may not be subjected to regulation. These results provide further support for the hypothesis that LDL modifications induced by arterial PG may contribute to the formation of foam cells. PMID- 2111369 TI - Apolipoprotein VLDL-II inhibits lipolysis of triglyceride-rich lipoproteins in the laying hen. AB - In the laying hen, very low density lipoprotein (VLDL) particles contain large amounts of apolipoprotein (apo)-VLDL-II in addition to apoB. These triglyceride rich lipoproteins are transported from the liver primarily to growing oocytes. Since no appreciable hydrolysis of triglyceride occurs during this transport, we have investigated the possibility that apoVLDL-II functions as an inhibitor of lipoprotein lipase (LPL). The presence of LPL in chicken follicular granulosa cells was demonstrated by immunoblotting, and LPL activity with the usual in vitro characteristics could be measured in cultured granulosa cell extracts. ApoVLDL-II inhibited LPL activity in these extracts as well as in the post heparin medium of rat cardiac myocytes. Half-maximal inhibition in both systems occurred at 40 micrograms/ml, a concentration that is one-tenth of the circulating apoVLDL-II in the laying hen. Much less inhibition was observed with reduced and alkylated apoVLDL-II and with apoA-I. We conclude that the presence of apoVLDL-II on laying hen VLDL ensures efficient delivery of triglyceride to the oocyte for subsequent use as energy source by the embryo. PMID- 2111370 TI - Lec9 CHO glycosylation mutants are defective in the synthesis of dolichol. AB - Lec9 Chinese hamster ovary cells were found previously to be defective in the synthesis of N-linked glycans. This appeared to be the result of a defect in the synthesis of oligosaccharide lipid and lipid phosphate (Rosenwald, Stanley, and Krag. 1989. Mol. Cell. Biol. 9: 914-924). In this study we analyzed the steady state levels of long-chain polyisoprenyl lipids in Lec9 cells. We found that Lec9 cells are defective in the synthesis of dolichol. They accumulated a presumed precursor to dolichol, cis-a-unsaturated polyprenol and used this lipid in the synthesis of oligosaccharide lipid. Chain lengths of the activated polyprenols in Lec9 were the same lengths as dolichols in parental cells. Lec9 cells had increased levels of monosaccharylphosphoryl lipid and decreased levels of oligosaccharylpyrophosphoryl lipid compared to parental cells. The defect in Lec9 cells was specific for dolichol synthesis, since other aspects of [3H]mevalonate metabolism in Lec9 cells were the same as in parental cells. We hypothesize that Lec9 cells are defective in polyprenol reductase activity. PMID- 2111371 TI - Pre- and postoperative evaluation of renal function with five different tests in patients with primary hyperparathyroidism. AB - Renal function was investigated immediately before and 1 year following parathyroidectomy in 19 patients with moderate hypercalcaemia. On both occasions, all patients underwent five different tests of glomerular and tubular function: plasma creatinine, creatinine clearance, 51Cr-EDTA-clearance, beta 2 microglobulin excretion and the desmopressin test. Glomerular filtration rate, as assessed by plasma creatinine and clearance of both creatinine and 51Cr-EDTA, was normal in most patients, and was little affected by restoration of normocalcaemia. Renal concentrating capacity, as determined by the desmopressin test, was abnormally low in 14 of 19 patients, but increased significantly after surgery. It is concluded that serious renal damage is seldom encountered in present-day HPT patients, but that a treatable decrease in renal concentrating capacity often exists. PMID- 2111372 TI - Mother to infant transmission of hepatitis C virus infection. AB - Eight women with chronic hepatitis C virus (HCV) infection during pregnancy gave birth to 11 children. Five of these children had elevated ALT, but only two had increased levels in more than one sample. All children tested before 6 months of age were positive for anti-HCV at most up to 7 months of age and then became negative. One child with a maximum ALT level of 8.4 mukat/l however, regained anti-HCV positivity at 12 months of age, and a liver biopsy at 21 months of age showed resolving hepatitis. Passively acquired HCV antibodies are obviously found in newborns of anti-HCV-positive mothers with chronic hepatitis. In 1 of 11 children, active anti-HCV production and concomitant liver disease suggested mother to infant transmission of hepatitis C virus infection. PMID- 2111373 TI - Cytokines alter target cell susceptibility to lysis: I. Evaluation of non-major histocompatibility complex-restricted effectors reveals differential effects on natural and lymphokine-activated killing. AB - Interferon-gamma (IFN) and tumor necrosis factor-alpha (TNF) were examined for their ability to enhance major histocompatibility complex (MHC) expression on a variety of human tumor and normal tissue targets. Enhanced expression of MHC correlated with decreased target susceptibility to lysis by fresh peripheral blood mononuclear cells (PBMCs) and IL-2-augmented PBMCs (aPBL) but not as clearly with cells with lymphokine-activated killer (LAK) activity. These studies revealed maximal MHC enhancement after 48-72 h of incubation in IFN. Resistance to lysis by natural killer (NK) cells was best demonstrated after 72 h. Further, IFN and TNF were synergistic in their effects on MHC expression and induction of resistance of the cultured leukemias K562 and Molt-4 to aPBL effectors. Conversely, LAK susceptibility was usually unaltered after target IFN and TNF treatment. Incubation of fibroblasts and vascular endothelial cells with IFN also consistently resulted in MHC class I enhancement and resistance to NK lysis, whereas LAK susceptibility was variably affected. The brief incubation of fresh PBL in IL-2 (4-6 h) resulted in effectors highly lytic toward cultured cells, but with no activity against fresh tumor. Cultured cell lines treated with IFN and TNF were rendered relatively resistant to lysis by these activated cells. Fresh tumor MHC expression and LAK susceptibility was unchanged after IFN incubation. Additionally, there was no correlation between the level of MHC class I or class II expression and LAK susceptibility to any fresh, uncultured melanoma studied. These data suggest that LAK effectors possess different mechanisms of tumor recognition or lysis than cells with NK activity or cells briefly incubated (4-6 h) in IL-2. The ability of tumor-infiltrating lymphocytes to lyse the cultured autologous tumor target was markedly increased by preincubation of the targets with IFN and TNF. Finally, it appears that IL-2 treatment and the resultant endogenous production of IFN by T-lymphocytes should not adversely affect tumor susceptibility to current immunotherapy using IL-2. PMID- 2111374 TI - Patterns of cytokines released by peripheral blood leukocytes of normal donors and cancer patients during interleukin-2 activation in vitro. AB - We have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL 2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon gamma (IFN-gamma), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines. In pattern I, exposure to the IL-2 resulted in a transient release of TNF during the first 48 h. The level of TNF released showed a progressive increase from PBLs harvested from the first cytapheresis (up to 50 pg of TNF/ml) through the fourth cytapheresis (up to 2,000 pg of TNF/ml). Additionally, pattern I PBLs showed significant levels of production of IFN-gamma, soluble IL-2 receptor, and soluble CD8. In pattern II, the patients' PBLs from each cytapheresis released only low levels of TNF (less than 300 pg/ml) and minimal levels of IFN-gamma, IL-2 receptor, and CD8. A pattern I response is considered to be consistent with an immunostimulatory role for IL-2, which induces a cooperative interaction of lymphocytes and macrophages that is mediated by other cytokines, while pattern II may reflect an immunosuppression in these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111375 TI - Secretion of interleukin-1 beta by a leukemia cell line in response to lipopolysaccharide and mezerein. AB - The acute monocytic leukemia cell line, THP-1, is frequently used as a model to study the mechanism of cell-mediated immune response. The model is justified, in part, because THP-1 cells can be induced to express features of activated peripheral blood monocytes or tissue macrophages. The current investigation, however, demonstrates that THP-1 cells differ from normal monocytes in their secretion of interleukin-1 beta (IL-1 beta) following exposure to reagents that induce synthesis. For example, LPS treatment alone did not result in IL-1 beta secretion and very low concentrations were observed when lipopolysaccharide (LPS) treated cells were simultaneously incubated with silica or silica in combination with hydroxyurea. Silica-enhanced release of IL-1 was related to changes in cell membrane permeability. Recombinant interferon-gamma (rIFN gamma) alone did not induce IL-1 beta secretion and did not significantly increase secretion by LPS- and silica-stimulated cells. In contrast, mezerein stimulation led to higher extracellular concentrations of IL-1 beta and rIFN gamma augmented secretion by mezerein-treated cells. Isoelectrofocusing of conditioned medium and titration of pooled fractions showed a direct correlation between extracellular levels of biologically active and immunoreactive IL-1. The role of IFN gamma in stimulating IL-1 beta secretion was not related to an enhancement of viability or an increase in the proportion of mezerein-treated cells synthesizing DNA. It was concluded that mezerein's regulation of secretion by THP-1 cells depended on the expression of monocyte features, including cell adherence and responsiveness to IFN gamma. PMID- 2111376 TI - Hemolytic anemia in a cancer patient treated with recombinant interferon-gamma. AB - Currently, three classes of interferon are used in the treatment of malignancies. Interferon-gamma is the best studied. Bone marrow suppression as well as immune hemolytic anemia have been described. Heretofore, only bone marrow suppression has been attributed to interferon-gamma (IFN gamma). In this report, we describe a woman with lung cancer being treated with IFN gamma in whom acute hemolytic anemia occurred. Immune hemolysis did not appear to be the cause. We concluded that in addition to bone marrow suppression, hemolysis should be considered in a patient receiving IFN gamma in whom an unexplained drop in hematocrit occurs. PMID- 2111377 TI - Modification of rat platelet fatty acid composition by dietary lipids of animal and vegetable origin. AB - There were no statistically significant differences in final body weight or in food intake among groups of rats fed for 7 wk various fats of animal origin (lard fat and cod liver oil) or vegetable origin (corn, soybean and canola oils); the fats were fed as 10% of the diet (by wt) and were of varied fatty acid composition. Nevertheless, the mean weights of the kidneys from cod liver oil-fed animals were significantly higher than those of all other dietary groups. Platelets of rats from the groups receiving the animal fat contained significantly lower levels of linoleic acid, 18:2(n-6) [a precursor of arachidonic acid, 20:4(n-6)], than did platelets from rats receiving the fat of vegetable origin. Although the soybean-, canola- and cod liver oil-fed animals received substantial quantities of (n-3) fatty acids [alpha-linolenic acid, 18:3(n-3); eicosapentaenoic acid, 20:5(n-3); and docosahexaenoic acid, 22:6(n 3)], only the platelets of the latter two groups contained detectable levels of these fatty acids along with their products of elongation/desaturation/retroconversion. Platelets of the cod liver oil-fed group contained significantly less arachidonic acid, a major precursor of eicosanoids, than did those from all other dietary groups. However, platelet arachidonic levels also varied markedly among the other dietary groups. Diet-induced fatty acid changes observed in platelets of various dietary groups may influence platelet responses, including secretion, aggregation and biosynthesis of eicosanoids. PMID- 2111378 TI - Catabolism of cyst(e)ine by rat renal cortical tubules. AB - Both cysteinesulfinate-independent and cysteinesulfinate-dependent pathways are involved in the catabolism of cyst(e)ine by freshly isolated rat renal cortical tubules. Sulfate and thiosulfate were shown to be the major sulfur-containing products that accumulated in incubations of renal tubules with 1 mmol/L or 25 mmol/L [35S]cyst(e)ine. Thiosulfate is an intermediate in the oxidation of the sulfide produced by the cysteinesulfinate-independent catabolism of cyst(e)ine by desulfhydration pathway(s), whereas sulfate is formed both by further oxidation of thiosulfate and by oxidation of the sulfite formed by the cysteinesulfinate transamination pathway. Incubation of renal tubules with propargylglycine inhibited gamma-cystathionase activity by 85%, and this resulted in a 46% decrease in sulfate production and a 68% decrease in thiosulfate production when the treated renal tubules were incubated with 1 mmol/L [35S]cyst(e)ine. Addition of 25 mmol/L unlabeled cysteinesulfinate to create a diluting/trapping pool for [35S]cysteinesulfinate formed from [35S]cysteine resulted in a 53% decrease in [35S]sulfate production in incubations with 1 mmol/L cysteine. Thus, some cyst(e)ine catabolism probably occurred by a cysteinesulfinate-dependent pathway. No production of taurine or hypotaurine was detected in incubations with cyst(e)ine. Thus, cysteinesulfinate formed from cysteine was further catabolized primarily to sulfate instead of to taurine and hypotaurine. Most cyst(e)ine catabolism by the epithelial cells of the renal tubule probably can be accounted for by two pathways: 1) the beta-cleavage of cystine catalyzed by lambda cystathionase and 2) the formation and transamination of cysteinesulfinate catalyzed by cysteine dioxygenase and aspartate aminotransferase. PMID- 2111379 TI - Modulation of pteroylpolyglutamate concentration and length in response to altered folate nutrition in a comprehensive range of rat tissues. AB - For a range of rat tissue extracts, the concentrations of total folates and of short-chain pteroylpolyglutamates were assayed by Lactobacillus casei with and without conjugase treatment, respectively, and the concentration and chain length of H4PteGlnn and 5,10-CH2-H4PteGlnn together were assayed after binding to thymidylate synthase and tritiated fluorodeoxyuridylate. For rats fed a nonpurified diet and consuming 26 micrograms of folic acid daily, the respective concentrations of these total folates, short-chain folates and thymidylate synthase bindable folates were, in nmol/g, 10.2, 2.5 and 3.5 in liver, 3.9, 1.8 and 2.0 in kidney, 4.2, 1.2 and 1.0 in bone marrow, 2.3, 0.6 and 0.2 in adrenal, 2.1, 0.3 and 0.5 in spleen, 2.1, 0.9 and 0.8 in jejunal smooth muscle, 1.2, 0.9 and 0.2 in jejunal mucosa, 1.0, 0.3 and 0.6 in testis, 0.7, 0.1 and 0.2 in heart, 0.3, 0.1 and 0.1 in skeletal muscle, 0.5, 0.1 and 0.3 in brain and 0.7, 0.002 and 0 in erythrocytes. The predominant pteroylpolyglutamate chain length was 6 residues in all tissues except kidney, jejunal mucosa, skeletal muscle and brain, in which the value was 5 residues. A folate-deficient diet (30 ng/d) fed for 3 wk resulted in a depression in the total folate concentration of all tissues (except brain); the depression was generally greater for short-chain than for long-chain folates and was accompanied by a lengthening of the pteroylpolyglutamate chain. Opposite results followed folate excess of 4 to 5.4 mg/d. The fractional change in the folate concentration of the individual tissues, following perturbation of dietary folate, did not vary greatly among tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111380 TI - Nutritional support. PMID- 2111381 TI - New trends in photobiology. The interaction of UVA radiation with cultured cells. AB - Recent work concerning the interaction of UVA radiation (320-380 nm) with cultured cells is reviewed with particular emphasis on the involvement of cellular oxidative stress in the biological effects of this radiation on eucaryotic cells. Possible chromophores are considered and their role in generation of various oxidant species including hydrogen peroxide, superoxide anion, singlet oxygen and hydroxyl radical. DNA and membranes are discussed as possible targets for the lethal action of long wavelength radiation. Four mechanisms of cellular defence are proposed: (1) DNA repair; (2) antioxidant enzymes; (3) endogenous free radical quenchers; (4) inducible protection. PMID- 2111382 TI - Time-resolved laser-induced fluorescence spectroscopy for enhanced demarcation of human atherosclerotic plaques. AB - We report on the enhanced demarcation between human atherosclerotic plaques and normal vessel wall obtained using time-resolved detection of laser-induced fluorescence rather than the customary time-integrated monitoring technique. A frequency-doubled mode-locked and cavity-dumped continuous wave dye laser was used for picosecond pulse generation at 320 nm, and photon-counting techniques were employed for the time-resolved signal monitoring from human aorta samples in vitro. Implications for imaging fluorescence angioscopy and spectroscopic guidance in laser ablation of plaque are indicated. PMID- 2111383 TI - Different lethal effects by enzyme-generated triplet indole-3-aldehyde in different Escherichia coli strains. AB - Strains of Escherichia coli which lack 4-thiouridine (S4U) exhibit a higher survival rate than their wild-type parents which contain S4U after treatment with enzyme-generated triplet indole-3-aldehyde. In a similar manner to results obtained with monochromatic 334 nm UV light, the survival is related to single strand breakage of DNA in E. coli containing the pBR 322 plasmid. The effects of the excited states generated by an enzymatic system suggest that S4U is an important chromophore in the lethal effects observed. The results also suggest that the energy transferred from triplet indole-3-aldehyde to S4U may also be passed from S4U of t-RNA to DNA, possibly through a singlet oxygen intermediate generated by excited S4U, resulting in a decrease in the survival rate of E. coli containing S4U. These results emphasize the importance of excited states in biological systems. PMID- 2111384 TI - Water-soluble metal naphthalocyanines--near-IR photosensitizers: cellular uptake, toxicity and photosensitizing properties in NHIK 3025 human cancer cells. AB - Metal naphthalocyanine complexes (MNCSs) absorb light in the near-IR spectral region (760 nm) where tissue penetration is optimal and they have been proposed as agents for photodynamic therapy (PDT). Sulphonated derivatives of tris-(2,3 naphthalocyanato) bis-chloroaluminium(III) and zinc(II) with various degrees of sulphonation were prepared. Cellular uptake, aggregation in cellular environments, cytotoxicity and photosensitizing properties were studied. Three of the four dyes studied were taken up by cells to a satisfactory degree and were not cytotoxic at the concentration used (10 micrograms ml-1). The least sulphonated sample of zinc naphthalocyanine produced some phototoxic effects (LD50 = 1.12 J cm-2). All the other samples of sulphonated naphthalocyanine were found to be aggregated inside the NHIK 3025 cells, preventing any significant PDT effect. PMID- 2111385 TI - Quantitative photoacoustic spectroscopy of cataractous human lenses. AB - Quantitative photoacoustic spectra of the nuclei of cataractous human lenses with various degrees of colouration and opacification were measured in the spectral range 250-600 nm. The lens nuclei were obtained from 20 cataractous patients through extracapsular cataract extraction. These measurements yield the light loss per unit path length in the nucleus of cataractous lenses. PMID- 2111386 TI - Mixed acenannellated metallotetraazaporphins: a new class of amphiphilic photosensitizers for the photodynamic therapy of cancer. AB - The first synthesis of amphiphilic mixed acenannellated metallotetraazaporphins compounds, designed with the aim of improving cell membrane penetration, is described and the preliminary results on their photocytotoxicity are presented. PMID- 2111387 TI - Retinal dopamine. PMID- 2111388 TI - Effects of UV radiation on motility, photo-orientation and pigmentation in a freshwater Cryptomonas. AB - The effects of UV radiation on photo-orientation, motility and pigmentation have been studied in a freshwater Cryptomonas species. The cells show a pronounced diaphototactic orientation which is affected by UV radiation at 50 mW m-2 within about 90 min. Both the average velocity of the swimming cells and the percentage of motile cells within the population decrease within about the same exposure time. UV radiation also bleaches the cellular pigments. PMID- 2111389 TI - A transient reduction of the fluorescence of aluminium phthalocyanine tetrasulphonate in tumours during photodynamic therapy. PMID- 2111390 TI - Synthesis and photobiological properties of acetylpsoralen derivatives. AB - In an investigation to find monofunctional reactants for DNA which can act as new agents in the photochemotherapy of psoriasis, we have synthesized and studied some methylpsoralen derivatives which contain an acetyl group at one of the two reactive sites of the furocoumarin skeleton (at the 3 or 5' positions). The compounds do not react easily with DNA; their photobiological properties (e.g. the lack of an ability to inhibit DNA synthesis in Ehrlich ascites tumour cells, to induce T2 phage sensitization and to induce erythema in guinea-pig skin) are exactly in line with this behaviour. Some interesting features are shown by 4,8 dimethyl-5'-acetylpsoralen: it is capable of producing a very large amount of singlet oxygen--an order of magnitude higher than the other compounds and 8 methoxypsoralen (used as reference). In spite of this property, 4,8-dimethyl-5' acetylpsoralen is non-phototoxic to the skin, and its other photobiological properties appear to be in line with its lack of interaction with DNA rather than its enhanced singlet oxygen production. PMID- 2111391 TI - Biosynthesis of phycobilins. Formation of the chromophore of phytochrome, phycocyanin and phycoerythrin. AB - Phycobiliproteins play important roles in photomorphogenesis and photosynthesis. The light-absorbing chromophores of the phycobiliproteins are linear tetrapyrroles (bilins) very similar in structure to the mammalian bile pigments. 5-Aminolaevulinate (5-ALA) is the first committed intermediate in phycobilin synthesis. The biosynthesis of 5-ALA, destined for phycobilins, occurs via the five-carbon pathway, now well established for tetrapyrrole synthesis in plants and distinct from the mammalian pathway. The phycobilins are formed by reduction of biliverdin which results from the synthesis and degradation of haem. This haem is an essential intermediate in the biosynthesis of phycobilins. Phycocyanobilin, the blue-green pigment found in certain algae and cyanobacteria, is formed from biliverdin via phytochromobilin, the chromophore of phytochrome. This leads to the likelihood that phytochromobilin is formed as an end product, or intermediate, in the synthesis of all phycobilins. PMID- 2111392 TI - Effect of replacing the primary quinone by different species on the ultrafast photosynthetic electron transfer in bacterial reaction centres. AB - Using picosecond absorption spectroscopy it has been shown that in Rhodobacter sphaeroides reaction centres the substitution of the primary quinone acceptor (QA), ubiquinone-10, by other quinone species (with redox potentials higher or lower than that of ubiquinone-10) has essentially no modifying effect on the reaction centre protein. The molecular relaxation processes that accompany the localization and stabilization of a photo-excited electron on the intermediate acceptor, bacteriopheophytin (I), are not affected, although the subsequent transfer of the electron from I to QA is slowed down. Consequently, this leads to a lower quantum efficiency of high rate of direct I-----QA reaction is normally due to the specificity of the primary quinone species and its binding site in the reaction centre protein which provide optimum steric and chemical conditions for an effective interaction between I and QA. PMID- 2111393 TI - Synthesis, cellular uptake of, and cell photosensitization by a porphyrin bearing a quinoline group. AB - A tetraphenyl porphine linked to a 7-chloroquinoline (5,10,15,20-tetraphenyl-1-3 [4-(4-aminobutyl)7-chloroquinoline] propioamidoporphine, TPPQ) was synthesized and examined as a potential photosensitizer for photodynamic therapy (PDT) of proliferative diseases. With respect to haematoporphyrin, TPPQ is a good in vitro photodynamic sensitizer producing singlet oxygen in 1% Triton X100 solutions. As with other hydrophobic porphyrins used in PDT, blood lipoproteins strongly bind TPPQ. Thus one low density lipoprotein (LDL) can incorporate 25 TPPQ molecules and 17 TPPQ molecules are taken up by one high density lipoprotein (HDL). Cell delivery of TPPQ using HDL or human serum albumin (HSA) as carrier is rather weak. However, an efficient TPPQ delivery to human skin fibroblasts is observed, partly aided by receptor-mediated endocytosis of LDL. Fluorescence spectroscopy shows that the cellular localization of TPPQ is both carrier and time dependent. During its delivery with LDL, TPPQ does not significantly impair the endocytosis of LDL-receptor complexes. After delivery with LDL, TPPQ is as efficient as other haematoporphyrin derivatives used in the PDT of cancers in photosensitizing human skin fibroblasts. PMID- 2111394 TI - Experimental tests of the feasibility of singlet oxygen luminescence monitoring in vivo during photodynamic therapy. AB - Singlet oxygen (1O2) is thought to be the cytotoxic agent in photodynamic therapy (PDT) with current photosensitizers. Direct monitoring of 1O2 concentration in vivo would be a valuable tool in studying biological response. Attempts were made to measure 1O2 IR luminescence during PDT of cell suspensions and two murine tumour models using the photosensitizers Photofrin II and aluminium chlorosulphonated phthalocyanine. Instrumentation was virtually identical to that devised by Parker in the one positive report of in vivo luminescence detection in the literature. Despite the fact that our treatments caused cell killing and tissue necrosis, we were unable to observe 1O2 emission under any conditions. We attribute this negative result to a reduction in 1O2 lifetime in the cellular environment. Quantitative calibration of our system allowed us to estimate that the singlet oxygen lifetime in tissue is less than 0.5 microsecond. Some technical improvements are suggested which would improve detector performance and perhaps make such measurements feasible. PMID- 2111395 TI - Photosensitization of mitochondria. Molecular and cellular aspects. PMID- 2111396 TI - Dark and photoreactivity of 4'-aminomethyl-4,5',8-trimethylpsoralen with T7 phage. AB - The dark and photoreactions of 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT) with T7 phage were investigated from biological and structural points of view. The dark reaction leads to the structural destabilization of the double helix of the DNA as is shown by optical melting measurements. The genotoxicity of AMT in the dark is comparable with that of known genotoxic drugs as determined by phage inactivation. The photoreaction with UVA light leads to the formation of mono- and di-adducts depending on the wavelength and dose used. Mono- and di-adducts influence DNA stability differently; biologically both types of adducts are genotoxic as measured by action spectra. PMID- 2111397 TI - Genetic effects and repair of DNA photo-adducts induced by 8-methoxypsoralen and homopsoralen (pyranocoumarin) in diploid yeast. AB - The relationship between DNA mono- and di-adducts and genetic effects induced by the pyranocoumarin 8,8-desmethylxanthyletine (homopsoralen) HP and 365 nm radiation (UVA) was investigated in the diploid yeast strain D7 (Saccharomyces cerevisiae) taking 8-methoxypsoralen (8-MOP) as a reference compound. The number of DNA cross-links (CLs) induced was determined using alkaline step elution analysis. The induction and removal of total photo-adducts was followed using radioactively labelled compounds. HP showed the same photobinding capacity as 8 MOP. As a function of UVA dose, it was less effective than 8-MOP for the induction of CLs and genetic effects. However, as a function of CLs induced, HP was shown to be more effective for the induction of lethal effects and mitotic recombination than 8-MOP but equally effective for the induction of mutations. The results suggest that, although CLs are recognized as genetically effective lesions, at a given number of CLs, HP induced mono-adducts efficiently contribute to the induction of lethal effects and mitotic recombination but less to the induction of mutations. Using a re-irradiation protocol, HP was brought to yield the same relative amounts of CLs at the same number of total adducts as single UVA exposures with 8-MOP. In these conditions, mutation induction and the kinetics for the removal of photo-adducts were the same for both agents indicating that not only the removal of adducts but also mutation induction are highly dependent on the relative level of CLs induced. PMID- 2111398 TI - Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice. AB - The biodistribution of a new and very potent photosensitizer, benzoporphyrin derivative-monoacid, ring A (BPD-MA), was determined in normal and P815 (mastocytoma) or M1 (rhabdomyosarcoma) tumor-bearing DBA/2J mice. A dose of 80 micrograms of 3H-BPD-MA was determined at 3, 24, 48, 72, 96 and 168 h post injection. The following tissues were tested: blood, brain, heart, intestine, kidney, lung, liver, muscle, skin, stomach, spleen, thymus and tumor. The biodistribution of 3H-BPD-MA in normal and tumor-bearing mice was comparable overall. 3H-BPD-MA localized in tumors better than in other tissues except kidney, liver and spleen. The tumor to tissue ratios were in the range 1.5-3 at 24 h post injection and increased further during the next 72 h. The highest levels of 3H-BPD-MA were observed in all tissues at 3 h post injection and decreased rapidly during the first 24 h. After 24 h the clearance from tissues was rather slow. The preliminary clearance data obtained in a group of five normal mice indicated that the majority of the injected dose (60%) cleared from the body via the bile and feces, while only about 4% cleared via kidneys and urine. Studies in which 3H-BPD-MA was extracted from tumor, kidney and liver 3 and 24 h after injection showed that, at 3 h, all the photosensitizing activity in tumor was retained. At 24 h only 39% of the activity was retained and considerably less active material was present in liver and kidney. PMID- 2111399 TI - Photophysical studies of pheophorbide a and pheophytin a. Phosphorescence and photosensitized singlet oxygen luminescence. AB - The triplet states of pheophorbide a and pheophytin a were studied in several environments by direct measurement of the phosphorescence of the pigments and photosensitized singlet oxygen (1O2) luminescence. The spectra, lifetimes and quantum yields of phosphorescence and the quantum yields of 1O2 generation were determined. These parameters are similar for monomeric molecules of both pigments in all the environments studied. Aggregation of the pigment molecules leads to a strong decrease in the phosphorescence and 1O2 luminescence intensities, which is probably due to a large decrease in the triplet lifetime and triplet quantum yield in the aggregates. The results obtained for pheophorbide a and pheophytin a are compared with those previously reported for chlorophyll alpha. The data suggest that the photodynamic activity of the pigments in living tissues is probably determined by the monomeric pigment molecules formed in hydrophobic cellular structures. Aggregated molecules seem to have a much lower activity. PMID- 2111400 TI - UVA hazards in skin associated with the use of tanning equipment--a comment. PMID- 2111401 TI - DNA photoreactivating enzyme from human tissues (S. E. Ogut, S. M. D'Ambrosio, M. Samuel and B. M. Sutherland, J. Photochem. Photobiol., B: Biol., 4 (1989) 47-56) PMID- 2111402 TI - Nucleic acids, DNA repair, photomutagenesis. PMID- 2111403 TI - Prevention of experimental cancer and immunostimulation by vitamin E (immunosurveillance). AB - Eighty young adult male Syrian hamsters were divided into four equal groups. Group 1 animals had the right buccal pouches painted with a 0.1% solution of 7,12 dimethylbenz(a)anthracene (DMBA) three times per wk for 28 wk. Group 2 animals were similarly painted with DMBA for 28 wk but were also given 140 micrograms vitamin E in 0.4 ml mineral oil three times weekly on days alternate to DMBA painting. Group 3 animals were used as DMBA-vehicle controls. Group 4 animals were vitamin E controls. Animals were killed after 28 wk, the pouches photographed and tumors counted, measured. The pouches were fixed in formalin, sectioned in paraffin and studied histologically and histochemically for tumor necrosis factors alpha and beta. All animals in Group 1 and 3 had gross tumors of the right buccal pouch. None of the animals in Group 2 had grossly visible tumors. Microscopic studies revealed that, while no gross tumors were seen in the Group 2 animals, there was histologic evidence of dysplasia and early carcinoma in-situ undergoing degeneration. Immunohistochemical staining revealed a dense infiltrate of mononuclear cells adjacent to tumor sites with a large number of cytotoxic T lymphocytes and macrophages. Vitamin E appears to prevent tumor formation by stimulating a potent immune response to selectively destroy tumor cells as they begin to develop into recognizable microscopic foci of carcinoma. PMID- 2111404 TI - Parkinsonian tremor and Waldenstrom's macroglobulinaemia. PMID- 2111405 TI - Expression of carbonic anhydrase in neisseriae and other heterotrophic bacteria. AB - A diverse range of heterotrophic bacteria was screened for the presence of carbonic anhydrase (CA) activity, sensitivity to inhibition of growth by acetazolamide (CA inhibitor), and the presence of protein binding monospecific antibody prepared against purified Neisseria sicca CA. CA activity was demonstrated only in strains of N. sicca and N. gonorrhoeae. However, all Neisseria strains, including various isolates of N. meningitidis and N. lactamica, were sensitive to acetazolamide, when grown in air, and showed serological cross-reaction with N. sicca CA. Strains of other genera were resistant to acetazolamide. A number of strains including members of the genera Pseudomonas, Staphylococcus, Streptococcus, Serratia and Proteus also strongly expressed a gene product(s) immunologically related to CA. The presence of CA cross-reacting proteins, which lack hydrase activity, is discussed in relation to the function of the various mammalian CA isoenzymes. PMID- 2111406 TI - Interactions of the oxygen-dependent antimicrobial system of the human neutrophil with difloxacin, ciprofloxacin, pefloxacin and fleroxacin in the intraphagocytic eradication of Staphylococcus aureus. AB - The effect of the O2-dependent antimicrobial systems of the human neutrophil on the intraphagocytic activity of difloxacin, ciprofloxacin, pefloxacin and fleroxacin was determined by use of a radioassay with Staphylococcus aureus as the test organism. The fluoroquinolones exhibited good intraphagocytic activity with normal neutrophils. However the intracellular bioactivities of the four antimicrobial agents were substantially less in tests with neutrophils from two patients with chronic granulomatous disease. These observations suggest a synergic interaction between fluoroquinolones and the O2-dependent antimicrobial systems of phagocytes in the eradication of intracellular microbial pathogens. PMID- 2111407 TI - Effects of incorporating ampicillin, bile salts and carbohydrates in media on the recognition and selection of Aeromonas spp. from faeces. AB - The effects of incorporating ampicillin, some bile salts and sugars into media on the primary recognition and selection of aeromonads from faeces were examined. Most (88%) of the 101 Aeromonas strains examined had an ampicillin MIC of greater than or equal to 40 mg/L, and would be isolated on blood agar containing ampicillin 30 mg/L. The strains with an ampicillin MIC of less than 40 mg/L were all of human origin and predominantly A. caviae. Although ampicillin at 10, 20 or 30 mg/L in blood agar inhibited faecal bacteria, the ability to detect Aeromonas strains with a high ampicillin MIC was less when the lower concentrations of ampicillin were used, without any improvement in the isolation of those strains with a low ampicillin MIC. Thirty-seven strains were tested for sensitivity to several different bile salts and found to be at least as resistant to them as Escherichia coli NCTC 10418. Bile salt sensitivity was not related to the species or source of a strain. There were minor differences in sensitivity to bile salts between some strains which related to whether strains had been isolated originally in the presence of bile salt or not. The effects of the presence of E. coli, Klebsiella spp. and Enterococcus faecalis on the growth of Aeromonas strains in mixed culture on media with and without carbohydrate were examined. The colony size of some Aeromonas strains was reduced in mixed culture but colony counts were not affected with any Aeromonas strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111408 TI - Power transmission along biological membranes. AB - Hypothesis on long-distance power transmission along extended energy-transducing membranes (Skulachev, 1969, 1971, 1980), has been experimentally proven in four different systems, namely, (i) trichomes of filamentous cyanobacterium Phormidium uncinatum; (ii) filamentous mitochondria and mitochondrial network in fibroblasts; (iii) clusters of roundish heart muscle mitochondria interconnected with mitochondrial junctions; (iv) mixed animal cell cultures interconnected with gap junctions. In all cases, energy was shown to be transmitted in the form of a transmembrane electric potential difference. The transmission occurred for distances as long as several tens of micrometers. Since the (a) delta-muH-bearing cytoplasmic membrane of cyanobacteria and the inner mitochondrial membrane and (b) delta-muNa-bearing outer animal cell membrane were found to be competent in such an effect, one may assume that the power transmission is a fundamental function of extended membrane systems. This mechanism can be used at the intracellular level (mitochondrial) as well as at the supracellular level (cytoplasmic and outer cell membranes). Studies on the possible involvement of membranes in lateral transport of oxygen, ions, fatty acids and membrane proteins seem to hold good promise. PMID- 2111409 TI - Crystallization of the arginine-dependent repressor/activator AhrC from Bacillus subtilis. AB - The arginine-dependent repressor/activator AhrC from Bacillus subtilis has been crystallized in space group C222(1), with unit cell dimensions a = 229.8 A, b = 72.8 A, c = 137.7 A and one aporepressor hexamer per asymmetric unit. Preliminary X-ray photographs show measurable intensities beyond 3.0 A. PMID- 2111410 TI - Determination of benzo[a]pyrene diol epoxide-DNA adducts in white blood cell DNA from coke-oven workers: the impact of smoking. AB - We have undertaken a study among coke-oven workers to test the feasibility of an enzyme-linked immunosorbent assay with anti-trans-7,8-dihydroxy-9,10-epoxy 7,8,9,10-tetrahydro-benzo[a]pyrene- DNA antibodies for monitoring occupational exposure to polycyclic aromatic hydrocarbons (PAH). Coke-oven workers are occupationally exposed to relatively high levels of PAH and are at increased risk for lung cancer. Three blood samples were collected from each of the 56 coke-oven workers exposed to PAH and 44 unexposed workers employed in a steel-rolling factory of the same plant. In addition, PAH levels were measured in ambient air by personal sampling, and the excretion of 1-hydroxypyrene in urine was also measured on 3 consecutive working days. All participants were interviewed regarding working conditions, personal hygiene, and smoking habits. The results showed that the coke-oven workers were exposed to substantial concentrations of atmospheric PAH (1-186 micrograms/m3), including benzo[a]pyrene (0.1-7.8 micrograms/m3) and pyrene (0.6-23.6 micrograms/m3). Both benzo[a]pyrene and pyrene were shown to be representative for the whole group of PAH. Forty-seven percent of the coke-oven workers had detectable levels of PAH-DNA adducts in their white blood cells, compared with 30% of the controls. In both groups, smokers had significantly higher levels of PAH-DNA adducts than did nonsmokers. At one site, we found the correlation positive between DNA adducts and the duration of exposure (r = .47, P = .005). Generally, the correlation was not significant between PAH-DNA adducts in blood and the concentration of PAH in the air and 1-hydroxypyrene in urine. PMID- 2111411 TI - In vivo antiproliferative effects of gamma-interferon and tumor necrosis factor alpha in a rat renal cell carcinoma model system. AB - We have investigated the antiproliferative activities of recombinant rat-gamma interferon and recombinant human tumor necrosis factor alpha in a rat renal cell carcinoma model system. The tumor was transplanted subcutaneously, the drugs were administered peritumorally. Gamma-interferon treatment starting two days after tumor implantation resulted in a dose-dependent growth inhibiting effect. Tumor necrosis factor alpha was only effective at the highest concentration. Different combinations of the drugs have additive or synergistic antiproliferative effects. The combination of both highest doses completely inhibited tumor growth without any obvious toxic effects on the rats. Rechallenge of the cured rats with a tumor piece in the contralateral flank did not result in a tumor specific immune response. Shortening of the treatment period to two weeks resulted in an increased lag-period, but finally all tumors started to grow. Furthermore, the anti-tumor effect was dependent on tumor volume at start of therapy. Monotherapy could not inhibit tumor growth of an established tumor. The combination with both highest doses, however, inhibited tumor growth even when treatment was started at a tumor volume of two to five cm3. Treatment with gamma-interferon and tumor necrosis factor is most effective at low tumor burden. These studies suggest that clinical application of these drugs is most effective in an adjuvant setting. PMID- 2111412 TI - Suture material in bladder surgery: a comparison of polydioxanone, polyglactin, and chromic catgut. AB - A comparison of polydioxanone, polyglactin, and chromic catgut suture was performed in 120 rat bladders studying propensity for infection, degree of inflammation, calculogenic potential, changes in urine pH, and suture absorption. None of the sutures predisposed to infection and there was wide variability but no correlation in urine pH. Although initially the polydioxanone incited a greater inflammatory response, by six months all three sutures were similar. The absorption of polydioxanone was slower than chromic catgut suture, but similar to the absorption of polyglactin. There was no significant difference in calculogenic potential between the suture materials tested over a six-month period. Based on this study in rats, polydioxanone suture would appear to be equal to catgut and polyglactin suture in bladder surgery. PMID- 2111413 TI - Regeneration of endothelial cells after balloon denudation of the rabbit carotid artery and changes in responsiveness. AB - The present experiments were carried out to determine the regrowth of endothelial cells (EC) after balloon denudation of the rabbit carotid artery and the changes in responsiveness of the artery with regenerated EC. Scanning electron microscopic findings revealed that 28.8% of the luminal surface was covered with regenerated EC at week 1. The regrowth of EC proceeded progressively, and a full lining was achieved at week 6. Regenerated EC were morphologically different from native ones; they were elongated (weeks 1 and 2) and irregularly oriented (weeks 4 and 6), and their numbers had significantly increased. Light microscopy revealed the intimal thickening and proliferation of smooth muscle cells. No accumulation of lipids in the vascular wall could be detected at any observation time. The experiments in an organ bath demonstrated that the altered appearance of EC was accompanied by depressed endothelium-dependent relaxations to acetylcholine, ADP and A23187. However, sodium nitroprusside-induced relaxation and contractile responses to noradrenaline, serotonin and histamine remained unchanged in the normal and denuded preparations, indicating that the dysfunction of the endothelium occurs at a time when the ability of the underlying vascular smooth muscle to relax or contract was unchanged. In addition, it is suggested that the impairment of the endothelium-dependent relaxation may be partly due to impairment of the synthesis and/or release of endothelium-derived relaxing factor(s) in EC. PMID- 2111415 TI - Prospective randomized controlled study on bestatin in resectable gastric cancer- third report. AB - The efficacy of Bestatin as adjuvant immunochemotherapy for patients with resectable gastric cancer was investigated. Ninety-six patients with similar background factors were randomized into two groups; a control group and an experimental group, the patients in the experimental group receiving a daily oral dose of 60 mg Bestatin over a long period. All 96 patients were treated with a bolus intravenous injection of mitomycin C (MMC) plus oral administration of tegafur (FT-207, FT). The survival rate of the patients in the MMC + FT + Bestatin group was more favorable than that of the patients in the MMC + FT group, but the difference was not statistically significant. The survival rates of the MMC + FT + Bestatin group patients in the stratification of stage III + IV and positive histological serosal invasion, ps(+), were significantly superior to those of the MMC + FT group patients (Logrank test: p less than 0.05). Moreover, in patients with positive histological serosal invasion, the recurrence of peritoneal dissemination was significantly suppressed in the MMC + FT + Bestatin group. PMID- 2111414 TI - Postoperative adjuvant immunochemotherapy with mitomycin C, tegafur, PSK and/or OK-432 for gastric cancer, with special reference to the change in stimulation index after gastrectomy. AB - In order to evaluate the efficacy of combined immunochemotherapy with mitomycin C, tegafur, PSK and/or OK-432 as an adjunct for curatively resected gastric cancer, a prospective randomized controlled study using the envelope method was performed, in which 266 institutions from around Japan participated. The 3 year survival rates for all cases, and for ps(+).n(+) cases, were insignificantly higher in the immunochemotherapy groups receiving PSK and/or OK-432 than in the control group. However, because 28.2 per cent of the cases were excluded from the final statistical analyses, the results of this study may have questionable statistical credibility. Changes in the stimulation index (SI) suggest that the administration of PSK may result in an inhibition of the immunosuppressive activity of cancer patients. The high SI group showed a significantly higher 4 year survival rate than the low SI group. PMID- 2111416 TI - Clinical trials of long-term RF local hyperthermia for advanced gastric cancer. AB - The effect of local hyperthermotherapy (HT) using 13.56-MHz radiofrequency (RF) capacitive heating was evaluated in 25 patients with unresectable or recurrent gastric cancer. HT was carried out once to 3 times a week for a duration of one hour at each session. Patients who underwent RF-HT frequently showed maintenance of performance status, symptomatic improvement and a reduction in tumor size. Moreover, the survival time of 9 patients who had numerous metastases to the distant peritoneum was significantly high (p less than 0.01), compared with 42 historical control patients who also had massive peritoneal dissemination, but had not received HT. The results of this study therefore indicate RF-HT to be a favorable modality in the palliative treatment of patients with far-advanced gastric cancer. PMID- 2111417 TI - Urinary excretion of kappa light chains in patients with diabetes mellitus. AB - The urinary excretion of kappa light chains, beta 2-microglobulin and albumin was examined in patients with newly diagnosed and long-standing insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus, and compared to age matched control subjects. Patients with IDDM diagnosed within two months, presented with normal albumin excretion, whereas the concentrations of beta 2 microglobulin and kappa light chain in urine were higher than in control subjects. The initiation of insulin therapy reduced, but did not completely normalize, the elevated rate of kappa light chain excretion. Patients with IDDM of long duration showed increased urine excretion of kappa light chains and albumin. In keeping with the findings in IDDM, patients with newly diagnosed NIDDM (within one year) showed increased urinary excretion of kappa light chains compared with control subjects. There was, however, no further increase in light chain excretion with longer duration of NIDDM. To study the effect of short-term hyperglycemia on urinary protein excretion, 12 normal subjects participated in a three-step hyperglycemic clamp study, during which their plasma glucose concentration was raised by +50, +125 and +300 mg/dl. The urine excretion of albumin and beta 2-microglobulin rose progressively with each hyperglycemic clamp step, whereas that of kappa light chain excretion was unaffected by hyperglycemia. We conclude that increased urinary excretion of kappa light chain is a consistent finding in all types of diabetes mellitus, and can be observed even when the albumin excretion is normal. Since the serum concentration of kappa light chain is normal in diabetes, the increased urinary excretion of kappa light chains must be of renal origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111419 TI - [Correction of protein and water-electrolyte metabolism disorders in patients with unformed fistulas of the small intestine]. AB - When treating 25 patients with the non-formed small intestinal fistulas, the use of alvesin "Novy" in the parenteral nutrition contributed to more intensive and effective correction of disorders in the protein and water-electrolyte metabolism as compared to that with the use of protein hydrolysates. PMID- 2111418 TI - Increased thromboxane biosynthesis in childhood hemolytic uremic syndrome. AB - Vascular endothelial cell damage plays a central role in the pathogenesis of the hemolytic uremic syndrome (HUS), resulting in intravascular platelet activation and thrombotic microangiopathy. A deficiency of the antiaggregatory prostacyclin (PGI2) has been postulated by experiments under ex vivo conditions. However, this observation has not been confirmed in vivo. The pathophysiological contribution of thromboxane (Tx)A2, a potent vasoconstrictor and platelet-aggregating prostanoid which is predominantly produced by platelets, has not been elucidated so far. In order to quantitate endogenous formation of TxA2 in children with HUS, plasma concentrations of the enzymatic metabolite 11-dehydro-TxB2 of TxA2 and urinary excretion rates of three major TxA2 metabolites, TxB2, 11-dehydro-TxB2 and 2,3-dinor-TxB2 were analyzed using gas chromatography/mass spectrometry. PGI2 biosynthesis was assessed by measuring urinary excretion of an index metabolite of its systemic production, 2,3-dinor-6-keto-prostaglandin (PG) F1 alpha, and an index of its renal production, 6-keto-PGF1 alpha. TxA2 biosynthesis was markedly elevated in the acute phase of HUS. This activation could be detected for a longer period of time than the presence of thrombocytopenia. Concomitantly in the acute phase, renal PGI2 formation was significantly elevated and systemic PGI2 formation was elevated in 50% of the patients. These data indicate that TxA2 formation is increased in the acute phase in patients with HUS. This enhanced biosynthesis is consistent with increased platelet activation, whereas the increased PGI2 biosynthesis reflects predominantly renal endothelial cell damage. PMID- 2111420 TI - [Diverticulosis of the duodenum as a rare cause of recurrent intestinal hemorrhage]. PMID- 2111421 TI - [Geriatric nursing 1990. Professional exhibition, and congress, 2/28-3/2/1990 in Hannover]. PMID- 2111422 TI - [Do we live at the expense of others? The worldwide intermeshing of nutrition, health and environment]. PMID- 2111423 TI - [More independence and professional satisfaction through the nursing process?]. PMID- 2111424 TI - [Continuing education within the framework of the European Nursing Students Group yearly meeting 1989, in Goteborg, Sweden]. PMID- 2111425 TI - [Nursing anamnesis and patient history questionnaires]. PMID- 2111426 TI - [Turkish patients in the hospital. Problems and proposals for solutions during their hospital stay]. PMID- 2111427 TI - [German nurses in a hospital in Switzerland]. PMID- 2111428 TI - [10 years German Society of Enterostomy Therapists]. PMID- 2111429 TI - [Literature search: a short description for nursing personnel]. PMID- 2111430 TI - Early and late complications of totally implantable venous access devices. AB - We reviewed the records of 66 consecutive patients who underwent placement of totally implantable venous access devices (TIVADs). Fourteen patients (21%) experienced complications related to the TIVAD. Complications included hematoma, infection, pneumothorax, subclavian vein thrombosis, and chronic clavicular pain. The 1 month mortality rate following insertion of a TIVAD was 24% (16 of 66 patients); however, none of the patients died as a direct consequence of port insertion or its associated complications. Overall patient and physician acceptance of TIVADs was good, and we encourage continued use and study of this device. PMID- 2111431 TI - [Mechanism of action of misoprostol]. PMID- 2111432 TI - An approach for immunodiagnosis of clinical cases of filariasis. AB - In this communication an immunodiagnostic approach has been adopted for detection of antigen and antibody in amicrofilaeamic Mf(-) patients by countercurrent immuno electrophoresis (CCIE) and immunodiffusion (ID). Using Setaria cervi and Immune Complex (IC) antigens, out of fifteen clinical cases the number of positive patients in CCIE were twelve and ten respectively. Sixty percent of the Mf(-) cases were positive in antigen detection against both the homologous and heterologous antibody. In ID nine Mf(-) cases gave precipitin bands against S. cervi antigen while with IC antigens ten patients were positive. In similar experiments, it was found that out of fifteen Mf(-) cases nine and eleven patients were positive in antigen detection against microfilaraemic Mf(+) sera and S. cervi antibody respectively. All the Mf(+) cases were positive in both antibody and antigen detection. From the standpoint of immunodiagnosis the data were analysed by two-way analysis of variance study and a newly developed system using Binomial distribution. The sera from the control group were negative in all the immunodiagnostic tests. PMID- 2111433 TI - [Long-term radiation injuries following neutron therapy]. AB - The paper is concerned with the data on late radiation injuries of normal tissues and critical organs in a group of 35 patients after fast neutron therapy in a period of 12 mos.-3.5 yrs. The value of radiation exposure of critical organs and tissues was considered for patients with head and neck tumors in relation to methods of fast neutron therapy and photon radiation with 60Co after a radical program. PMID- 2111434 TI - Outbreak of multidrug-resistant tuberculosis--Texas, California, and Pennsylvania. PMID- 2111435 TI - Occupational fatalities associated with exposure to epoxy resin paint in an underground tank--Makati, Republic of the Philippines. PMID- 2111436 TI - Update: serologic testing for HIV-1 antibody--United States, 1988 and 1989. PMID- 2111437 TI - Mutational mapping of RAS-responsive domains of the Saccharomyces cerevisiae adenylyl cyclase. AB - Large deletion and small insertion mutations in the adenylyl cyclase gene of Saccharomyces cerevisiae were used to map regions required for activation by RAS protein in vitro. The amino-terminal 605 amino acids were found to be dispensable for responsiveness to RAS protein. All other deletions in adenylyl cyclase destroyed its ability to respond to RAS. Small insertion mutations within the leucine-rich repeat region also prevented RAS responsiveness, while other insertions did not. PMID- 2111438 TI - Molecular cloning and biological characterization of the human excision repair gene ERCC-3. AB - In this report we present the cloning, partial characterization, and preliminary studies of the biological activity of a human gene, designated ERCC-3, involved in early steps of the nucleotide excision repair pathway. The gene was cloned after genomic DNA transfection of human (HeLa) chromosomal DNA together with dominant marker pSV3gptH to the UV-sensitive, incision-defective Chinese hamster ovary (CHO) mutant 27-1. This mutant belongs to complementation group 3 of repair deficient rodent mutants. After selection of UV-resistant primary and secondary 27-1 transformants, human sequences associated with the induced UV resistance were rescued in cosmids from the DNA of a secondary transformant by using a linked dominant marker copy and human repetitive DNA as probes. From coinheritance analysis of the ERCC-3 region in independent transformants, we deduce that the gene has a size of 35 to 45 kilobases, of which one essential segment has so far been refractory to cloning. Conserved unique human sequences hybridizing to a 3.0-kilobase mRNA were used to isolate apparently full-length cDNA clones. Upon transfection to 27-1 cells, the ERCC-3 cDNA, inserted in a mammalian expression vector, induced specific and (virtually) complete correction of the UV sensitivity and unscheduled DNA synthesis of mutants of complementation group 3 with very high efficiency. Mutant 27-1 is, unlike other mutants of complementation group 3, also very sensitive toward small alkylating agents. This unique property of the mutant is not corrected by introduction of the ERCC-3 cDNA, indicating that it may be caused by an independent second mutation in another repair function. By hybridization to DNA of a human x rodent hybrid cell panel, the ERCC-3 gene was assigned to chromosome 2, in agreement with data based on cell fusion (L. H. Thompson, A. V. Carrano, K. Sato, E. P. Salazar, B. F. White, S. A. Stewart, J. L. Minkler, and M. J. Siciliano, Somat. Cell. Mol. Genet. 13:539-551, 1987). PMID- 2111439 TI - Effects of expression of mammalian G alpha and hybrid mammalian-yeast G alpha proteins on the yeast pheromone response signal transduction pathway. AB - Scg1, the product of the Saccharomyces cerevisiae SCG1 (also called GPA1) gene, is homologous to the alpha subunits of G proteins involved in signal transduction in mammalian cells. Scg1 negatively controls the pheromone response pathway in haploid cells. Either pheromonal activation or an scg1 null mutation relieves the negative control and leads to an arrest of cell growth in the G1 phase of the cell cycle. Expression of rat G alpha s was previously shown to complement the growth defect of scg1 null mutants while not allowing mating. We have extended this analysis to examine the effects of the short form of G alpha s (which lacks 15 amino acids present in the long form), G alpha i2, G alpha o, and Scg1 mammalian G alpha hybrids. In addition, we have found that constructs able to complement scg1 are also able to inhibit the response to pheromone and mating when expressed in a wild-type SCG1 strain. Overexpression of Scg1 has a similar inhibitory effect. These results are consistent with a model proposed for the action of Scg1 as the alpha component of a heterotrimeric G protein in which the beta gamma component (Ste4/Ste18) activates the pheromone response after dissociation from Scg1. They suggest that the G alpha constructs able to complement scg1 can interact with beta gamma to prevent activation of the pathway but are unable to interact with pheromone receptors to activate the pathway. PMID- 2111440 TI - The immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription. AB - We demonstrate that the immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription. The enhancer itself, when placed 5' to the bacterial cat or neo genes, is able to direct transcription by using heterogeneous start sites that are generally the same as those found with bona fide I mu transcripts. In general, promoter activity is dependent on the same sequence motifs important for enhancer activity. However, it appears that a mutation within the conserved octanucleotide ATTTGCAT has a much more severe effect on the promoter activity of the enhancer than the same mutation has on its enhancer activity. This result is consistent with the known role of the octanucleotide as a promoter element, and this is discussed in relation to the biological role of sterile transcription. PMID- 2111441 TI - Tissue and subcellular distributions of the smg-21/rap1/Krev-1 proteins which are partly distinct from those of c-ras p21s. AB - We have made a specific antiserum recognizing both smg p21A (the rap1A/Krev-1 protein) and -B (the rap1B protein), ras p21-like GTP-binding proteins having the same putative effector domain as ras p21s and have used this antiserum to study the tissue and subcellular distributions of smg p21s by immunoblot and immunocytochemical analyses. By immunoblot analysis, smg p21s were detected in various rat tissues and at the highest level in brain. By light microscopic immunocytochemical analysis, smg p21s were also detected in various rat tissues. Particularly, smg p21s in brain were found abundantly in the cytoplasmic region of most types of neuronal cell bodies and moderately in neuropil, whereas c-ras p21s were found more abundantly in neuropil than in the cytoplasmic region of most types of neuronal cell bodies. smg p21s in testis were found in spermatogenic cells, in which c-ras p21s were not significantly detected. By subcellular fractionation analysis of cerebrum, smg p21s were detected in all of the particulate fractions but not in the cytosol fraction. Among the particulate fractions, approximately 70% of smg p21s was recovered with the highest specific content in the fraction containing mainly synaptosomes, mitochondria, and myelin. In further fractionation of this fraction, approximately 40% of smg p21s was recovered in each of the synaptosome fraction and the mitochondrial fraction. This subcellular distribution of smg p21s in cerebrum was partly distinct from that of c-ras p21s, which were mainly recovered in the synaptosome and microsome fractions but present at very low levels in the mitochondrial fraction. These tissue and subcellular distributions of smg p 21s together with the fact that smg p21s have the same putative effector domain as ras p21s exert their own specific actions in addition to the actions similar or antagonistic to those of c-ras p21s. PMID- 2111442 TI - Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1 responsive element in the IL-6 gene. AB - The interleukin-6 (IL-6) promoter is rapidly and transiently activated with other cytokines, including IL-1, tumor necrosis factor, and platelet-derived growth factor, as well as phorbol esters and agents that increase intracellular cyclic AMP. In this study, we have investigated cis-acting regulatory elements and trans acting factors responsible for IL-1-induced IL-6 gene expression. Studies on the 5' deletion mutants of the human IL-6 gene suggested that the IL-1-responsive element was mapped within the IL-6 promoter region (-180 to -123) which was homologous to the c-fos serum-responsive enhancer element. Gel retardation assay identified two types of nuclear factors that bound to this region, one constitutive and the other inducible. These two factors recognized a 14-base-pair (bp) palindromic sequence, ACATTGCACAATCT. Furthermore, three copies of this 14 bp palindrome conferred IL-1 responsiveness to the basal enhancerless IL-6 promoter, indicating that a 14-bp-dyad symmetry sequence was an IL-1-responsive element in the IL-6 gene. PMID- 2111443 TI - Oncogenic transformation by vrel requires an amino-terminal activation domain. AB - The mechanism by which the products of the v-rel oncogene, the corresponding c rel proto-oncogene, and the related dorsal gene of Drosophila melanogaster exert their effects is not clear. Here we show that the v-rel, chicken c-rel, and dorsal proteins activated gene expression when fused to LexA sequences and bound to DNA upstream of target genes in Saccharomyces cerevisiae. We have defined two distinct activation regions in the c-rel protein. Region I, located in the amino terminal half of rel and dorsal proteins, contains no stretches of glutamines, prolines, or acidic amino acids and therefore may be a novel activation domain. Lesions in the v-rel protein that diminished or abolished oncogenic transformation of avian spleen cells correspondingly affected transcription activation by region I. Region II, located in the carboxy terminus of the c-rel protein, is highly acidic. Region II is not present in the v-rel protein or in a transforming mutant derivative of the c-rel protein. Our results show that the oncogenicity of Rel proteins requires activation region I and suggest that the biological function of rel and dorsal proteins depends on transcription activation by this region. PMID- 2111444 TI - Activation of the proto-oncogene p60c-src by point mutations in the SH2 domain. AB - To investigate the importance of a conserved region spanning residues 137 to 241 in the noncatalytic domain of p60c-src (SH2 region), we used oligonucleotide directed mutagenesis to change residues that are highly conserved in this region. Chicken embryo fibroblasts infected with a p60c-src variant containing arginine instead of tryptophan at residue 148 (W148R) appeared more rounded than cells overexpressing a normal c-src gene, and they formed colonies in soft agar. p60c src variants containing serine instead of arginine at residue 155 (R155S) or isoleucine instead of glycine at residue 170 (G170I) also appeared transformed and were anchorage independent, but to a lesser extent than W148R. Mutation of residue 201 from histidine to leucine (H201L) had no observable effect. The in vitro kinase activity of cells infected with W148R or G170I was elevated twofold. Expression of p60W148R (or, to a lesser extent, of p60G170I) increased the number of proteins phosphorylated on tyrosine in infected cells. All of the mutants were phosphorylated in vivo on Tyr-527, instead of Tyr-416 as observed for p60v-src. Immunoprecipitated p60W148R and p60G170I were found to be associated with a phosphatidylinositol kinase activity, a factor which appears to be necessary for transformation by tyrosine-specific protein kinases. These results show that a single point mutation in the SH2 region of the cellular src gene can activate its transforming potential. This type of activation is in a new category of alterations at the amino terminus that activate but do not cause a shift in phosphorylation at the carboxy terminus. PMID- 2111445 TI - Mutations in cell division cycle genes CDC36 and CDC39 activate the Saccharomyces cerevisiae mating pheromone response pathway. AB - Conditional mutations in the genes CDC36 and CDC39 cause arrest in the G1 phase of the Saccharomyces cerevisiae cell cycle at the restrictive temperature. We present evidence that this arrest is a consequence of a mutational activation of the mating pheromone response. cdc36 and cdc39 mutants expressed pheromone inducible genes in the absence of pheromone and conjugated in the absence of a mating pheromone receptor. On the other hand, cells lacking the G beta subunit or overproducing the G alpha subunit of the transducing G protein that couples the receptor to the pheromone response pathway prevented constitutive activation of the pathway in cdc36 and cdc39 mutants. These epistasis relationships imply that the CDC36 and CDC39 gene products act at the level of the transducing G protein. The CDC36 and CDC39 gene products have a role in cellular processes other than the mating pheromone response. A mating-type heterozygous diploid cell, homozygous for either the cdc36 or cdc39 mutation, does not exhibit the G1 arrest phenotype but arrests asynchronously with respect to the cell cycle. A similar asynchronous arrest was observed in cdc36 and cdc39 cells where the pheromone response pathway had been inactivated by mutations in the transducing G protein. Furthermore, cdc36 and cdc39 mutants, when grown on carbon catabolite derepressing medium, did not arrest in G1 and did not induce pheromone-specific genes at the restrictive temperature. PMID- 2111446 TI - Complex regulation of the immunoglobulin mu heavy-chain gene enhancer: microB, a new determinant of enhancer function. AB - The B-lymphocyte-specific activity of the immunoglobulin mu heavy-chain gene enhancer has been attributed to the octamer motif (ATTTGCAT) present within the enhancer that binds a B-cell-specific factor designated NF-A2/OTF-2. However, significant residual enhancer activity even after deletion of this element has suggested the presence of a second critical functional determinant. We have used deletion and mutational analyses to define an element, microB (TTTGGGGAA), that is essential for B-cell-specific enhancer activity in S194 myeloma cells in the absence of the octamer. Transfection analysis in a panel of lymphoid cell lines suggests that the presence of either microB or octamer leads to considerable enhancer activity in cell lines representing later stages of B-cell differentiation, whereas both elements are needed for function in cell lines representing earlier stages. Furthermore, in contrast to the results in pre-B cell lines, both microB and octamer elements function independently in certain T cell lines in which the mu enhancer is active. PMID- 2111447 TI - Involvement of a second lymphoid-specific enhancer element in the regulation of immunoglobulin heavy-chain gene expression. AB - To determine whether enhancer elements in addition to the highly conserved octamer (OCTA)-nucleotide motif are important for lymphoid-specific expression of the immunoglobulin heavy-chain (IgH) gene, we have investigated the effect of mutating the binding site for a putative additional lymphoid-specific transcription factor, designated NF-microB, in the murine IgH enhancer. We demonstrate that the NF-microB-binding site plays a critical role in the IgH enhancer, because mutation of the microB DNA motif decreased transcriptional activity of the IgH enhancer in cells of the B-cell lineage but not in nonlymphoid cells. This effect was comparable to or even stronger than the effect of a mutation in the OCTA site. Moreover, combined mutation of both microB and OCTA sites further reduced enhancer activity in lymphoid cells. Interestingly, alteration of either the microB or E3 site in a 70-base-pair fragment of the IgH enhancer that lacks the binding site for OCTA abolished enhancer activity in lymphoid cells completely. Nevertheless, a multimer of the microB motif alone showed no enhancer activity. DNase footprinting analysis corroborated the functional data showing that a lymphoid-specific protein binds to the microB DNA motif. Our results suggest that the microB element is a new crucial element important for lymphoid-specific expression of the IgH gene but that interaction with another enhancer element is essential for its activity. PMID- 2111448 TI - Structure of the DNA damage-inducible gene DDR48 and evidence for its role in mutagenesis in Saccharomyces cerevisiae. AB - The DDR48 gene of Saccharomyces cerevisiae is a member of a set of genes that displays increased transcription in response to treatments that produce DNA lesions or to heat-shock stress. Other members of this group include the DDRA2 and UBI4 genes. DNA sequence analysis of the DDR48 gene demonstrates the presence of two overlapping open reading frames, each of which has the capacity to encode a protein with a molecular mass of approximately 45 kilodaltons. Fusions of the DDR48 coding sequences to lacZ demonstrates that only one of these frames is expressed in yeast cells. The protein predicted from this sequence is extremely hydrophilic and contains multiple repeats of the peptide sequence Ser-Asn-Asn-X Asp-Ser-Tyr-Gly where X is either Asn or Asp. Additionally, closely related sequences are found throughout the primary sequence. Primer extension data indicate that, after 4-nitroquinoline-1-oxide and heat-shock treatments, there are three major and two minor transcriptional start sites which are utilized. The function of the DDR48 gene was investigated by disrupting this gene in diploid cells. Viable haploid cells containing the DDR48 gene disruption were isolated after tetrad analysis. Although the ddr48 mutant showed a slightly altered sensitivity to killing by 4-nitroquinoline-1-oxide and to heat shock compared with the DDR48 haploid, the spontaneous mutation rate of reversion of a his4 mutation was reduced 6- to 14-fold in the ddr48 strain. These results implicate the DDR48 gene in the production or recovery of mutations in S. cerevisiae. PMID- 2111449 TI - c-myc, c-fos, and c-jun regulation in the regenerating livers of normal and H 2K/c-myc transgenic mice. AB - We investigated the mechanisms of regulation of c-myc, c-fos, and c-jun at the early stages of liver regeneration in mice. We show that the transient increase in steady-state levels of c-myc mRNA at the start of liver regeneration is most probably regulated by posttranscriptional mechanisms. Although there was a marked increase in c-myc transcriptional initiation shortly after partial hepatectomy, a block in elongation prevented the completion of most transcripts. To gain further information on the mechanism of regulation of c-myc expression during liver regeneration, we used transgenic mice harboring the human c-myc gene driven by the H-2K promoter. In these animals, the murine c-myc responded to the growth stimulus generated by partial hepatectomy, whereas the expression of the transgene was constitutive and did not change in the regenerating liver. However, the mRNA from both genes increased markedly after cycloheximide injection, suggesting that the regulation of c-myc mRNA abundance in the regenerating liver differs from that occurring after protein synthesis inhibition. Furthermore, we show that in normal mice c-fos and c-jun mRNA levels and transcriptional rates increase within 30 min after partial hepatectomy. c-fos transcriptional elongation was restricted in nongrowing liver, but the block was partially relieved in the regenerating liver. Nevertheless, for both c-fos and c-jun, changes in steady-state mRNA detected after partial hepatectomy were much greater than the transcriptional increase. In the regenerating liver of H-2K/c-myc mice, c-fos and c-jun expression was diminished, whereas mouse c-myc expression was enhanced in comparison with that in nontransgenic animals. PMID- 2111450 TI - Ongoing diversification of the rearranged immunoglobulin light-chain gene in a bursal lymphoma cell line. AB - The chicken immunoglobulin light-chain gene (IgL) encodes only a single variable gene segment capable of recombination. To generate an immune repertoire, chickens diversify this unique rearranged VL gene segment during B-cell development in the bursa of Fabricius. Sequence analysis of IgL cDNAs suggests that both gene conversion events derived from VL segment pseudogene templates (psi VL) and non template-derived single-base-pair substitutions contribute to this diversity. To facilitate the study of postrecombinational mechanisms of immunoglobulin gene diversification, avian B-cell lines were examined for the ability to diversify their rearranged IgL gene during in vitro passage. One line that retains this ability, the avian leukosis virus-induced bursal lymphoma cell line DT40, has been identified. After passage for 1 year in culture, 39 of 51 randomly sequenced rearranged V-J segments from a DT40 population defined novel subclones of the parental tumor. All cloned V-J segments displayed the same V-J joint, confirming that the observed diversity arose after V-J rearrangement. Most sequence variations that we observed (203 of 220 base pairs) appeared to result from psi VL-derived gene conversion events; 16 of the 17 novel single nucleotide substitutions were transitions. Based on these data, it appears that immunoglobulin diversification during in vitro passage of DT40 cells is representative of the diversification that occurs during normal B-cell development in the bursa of Fabricius. PMID- 2111451 TI - Molecular and developmental characterization of the heat shock cognate 4 gene of Drosophila melanogaster. AB - The Drosophila heat shock cognate gene 4 (hsc4), a member of the hsp70 gene family, encodes an abundant protein, hsc70, that is more similar to the constitutively expressed human protein than the Drosophila heat-inducible hsp70. Developmental expression revealed that hsc4 transcripts are enriched in cells active in endocytosis and those undergoing rapid growth and changes in shape. PMID- 2111452 TI - Closely related DNA sequences specify distinct patterns of developmental expression in Drosophila melanogaster. AB - Three short synthetic DNA sequences, which are closely related to one another, confer three distinct patterns of developmental expression on the heat shock hsp70 gene in transgenic Drosophila melanogaster lines. These results show that small variations or even single base pair changes in a repeated element of a regulatory sequence can create promoters that display new specificities of tissue and developmental regulation. Interestingly, the three patterns of developmental expression conferred by the synthetic DNAs resemble in part those of the known developmental genes: glucose dehydrogenase (Gld), Dopa decarboxylase (Ddc), and salivary gland secretory proteins (Sgs), respectively. In each case, the defined regulatory region of the known developmental gene contains multiple sequences that are similar or identical to the synthetic sequence that confers a similar pattern of developmental expression on the hsp70 gene. Thus, these results are congruent with the view that short sequence elements in multiple copies can confer either simple or relatively complex patterns of developmental expression on a receptive promoter like that of hsp70. Furthermore, the fact that the three variants tested produced three distinct patterns of expression in transgenic animals suggests that the number of different elements is large. PMID- 2111453 TI - Effects of thyroid hormone deficiency and replacement on rat hypothalamic growth hormone (GH)-releasing hormone gene expression in vivo are mediated by GH. AB - The role of thyroid hormone and GH in the regulation of hypothalamic GH-releasing hormone (GRH) gene expression in the rat was examined after the induction of thyroid hormone deficiency by thyroidectomy. Thyroidectomy resulted in a time dependent decrease in hypothalamic GRH content, which was significant by 2 weeks postoperatively, and a reduction in pituitary GH content to 1% of the control level by 4 weeks. In contrast, GRH secretion by incubated hypothalami under both basal and K(+)-stimulated conditions was increased after thyroidectomy. Hypothalamic GRH mRNA levels also exhibited a time-dependent increase, which was significant at 1 week and maximal by 2 weeks after thyroidectomy. Administration of antirat GH serum to thyroidectomized rats resulted in a further increase in GRH mRNA levels. T4 treatment of thyroidectomized rats for 5 days, which also partially restored pituitary GH content, lowered the elevated GRH mRNA levels. However, comparable effects on GRH mRNA levels were observed by rat GH treatment alone. These results suggest that the changes in hypothalamic GRH gene expression after thyroidectomy in the rat are due to the GH deficiency caused by thyroidectomy, rather than a direct effect of thyroid hormone on the hypothalamus, since the changes were reversible by GH alone despite persistent thyroid hormone deficiency. In addition, they further support the role of GH as a physiological negative feedback regulator of GRH gene expression. PMID- 2111454 TI - Structural and functional similarities of breadfruit seed lectin and jacalin. AB - Aquous extracts from seeds of Artocarpus altilis (breadfruit) and Artocarpus heterophyllus (jackfruit) were compared by polyacrylamide gel electrophoresis. Two bands of the same size (12 and 15 kD) as the jacalin subunits were the major components in breadfruit seed extract. They strongly reacted with anti-jacalin antibodies by western blotting. The breadfruit lectin displayed the same IgAl and IgD precipitation specificity as jacalin in gel double diffusion experiments. It also stimulated in vitro proliferation of human peripheral blood mononuclear cells. These results suggest that lectins from both species of Artocarpus are very similar. PMID- 2111455 TI - Functional interactions of red cells sensitized by IgG1 and IgG3 human monoclonal anti-D with enzyme-modified human monocytes and FcR-bearing cell lines. AB - Human monoclonal IgG1 and IgG3 antibodies specific for the Rh antigen D (anti-D) were tested for their ability to promote the binding of D-positive red cells to peripheral blood monocytes and Fc receptor (FcR)-bearing cell lines (U937, K562 and Daudi). Monocyte-mediated antibody-dependent cell-mediated cytotoxicity and metabolic (chemiluminescent) responses were also determined. By comparing the activity of different cell lines in rosette assays, and by using murine myeloma IgG2a and IgG1 to block FcRI and FcRII respectively, these functional interactions of sensitized red cells (E-IgG1 and E-IgG3) with monocytes or cell lines were shown to be mediated predominantly and perhaps solely by FcRI. E-IgG3 bound to human monocytes and cell lines to a greater extent than E-IgG1. Rosette formation by E-IgG3 was relatively less susceptible to inhibition by fluid-phase murine IgG2a than was rosette formation by E-IgG1. These findings may be due to the long hinge region of IgG3 which enables it to bridge the gap between two negatively charged cells more efficiently than IgG1. Consistent with this hypothesis was the greatly increased rosette formation achieved by treating monocytes or U937 cells with neuraminidase or bromelain, procedures shown to reduce the zeta potential of these cells. The lytic and metabolic activities of untreated human monocytes were also greater towards E-IgG3 than E-IgG1, red cell binding being a prerequisite for these responses. However, after pretreatment of monocytes with neuraminidase, these responses were greater with E-IgG1 than with E-IgG3. Further, the addition of polybrene to non-specifically enhance cell to cell binding also resulted in greater lysis and chemiluminescence with E-IgG1 than with E-IgG3. These results indicate that, although E-IgG3 are more effective than E-IgG1 in promoting red cell binding to monocytes, E-IgG1 are more efficient at activating the lytic and metabolic processes providing the steric disadvantages of the shorter hinge region of cell-bound IgG1 are circumvented. PMID- 2111456 TI - Investigation of the SOS response of Escherichia coli after gamma-irradiation by means of the SOS chromotest. AB - The kinetics of SOS system induction in Escherichia coli PQ37 cells by gamma irradiation has been studied by the SOS chromotest technique. It was shown that the synthesis of constitutive alkaline phosphatase is not immediately stopped in cells that suffered lethal damages from gamma-irradiation. The production of DNA damages inducing the SOS system was 0.021/Gy per genome. The SOS system was switched off approximately 200 min after gamma-irradiation. A correction is proposed to the calculation of the SOS system induction factor. PMID- 2111457 TI - A quantitative assay for measuring the induction of mutations in human peripheral blood T-lymphocytes. AB - We optimized conditions for propagating freshly-isolated human peripheral blood T lymphocytes and cells that had been stored in liquid nitrogen on Day 5 post isolation, exposing them to mutagens in exponential growth, and measuring the cytotoxicity of the agent from the loss of colony-forming ability, and its mutagenicity from the increase in frequency of 6-thioguanine-resistant cells. Supernatant containing T-cell growth factor, from 60Co-irradiated peripheral mononuclear cells cultured in the presence of 60Co-irradiated B-lymphoblastoid human cells as allogeneic stimulators, supplied at a concentration of 10% along with 10% serum and 10(5) allogeneic stimulator cells/ml, supported exponential growth (population doubling times of 22 h) for extended periods (greater than 30 d). It gave cloning efficiencies of greater than or equal to 40%. T-lymphocytes stored in liquid nitrogen and returned to culture shortly before mutagen exposure exhibited the same sensitivity as freshly-isolated T-cells to killing by the agents tested, i.e., UV radiation, ethyl-nitrosourea, and (+/-)-7 beta,8 alpha dihydroxy-9 alpha,19 alpha,epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene. We showed that if mutagenized populations frozen during the expression period were thawed and assayed, they exhibited the same cloning efficiencies and frequencies of 6 thioguanine-resistant cells as did the corresponding populations that had been assayed directly without freezing. Use of these procedures should facilitate investigation of the frequency and kinds of mutations induced in the HPRT gene of peripheral blood T-lymphocytes in vivo and in vitro. PMID- 2111458 TI - Dietary fat modifies the in vivo mutagenicity of some food-borne carcinogens. AB - Female BALB/c mice were fed a low fat diet (1% safflower oil, by weight) or one supplemented with 25% (by weight) of beef fat or olive oil. The abilities of these diets to modify the in vitro and in vivo hepatic conversion of the dietary carcinogens aflatoxin B1, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) to bacterial mutagens was evaluated. Dietary olive oil appeared to increase the metabolism of both MeIQ and Trp-P-2 to bacterial mutagens in vivo using the intrasanguineous host-mediated assay. Feeding mice either of the high-fat diets increased hepatic conversion of these two compounds to bacterial mutagens in vitro. Dietary fat had no effect on the metabolism of aflatoxin B1. Subsequent experiments suggested that the in vivo effects of dietary olive oil on MeIQ and Trp-P-2 mutagenesis were due to the induction of hepatic enzyme activities rather than to increased rates of uptake of the carcinogen from the gut-lumen. PMID- 2111459 TI - In vitro and in vivo reactions of nucleic acids with reducing sugars. AB - Reducing sugars such as glucose and glucose 6-phosphate have been shown to nonenzymatically react with the amino groups of proteins. The modification of proteins by reducing sugars can alter both physical characteristics and biological functions. Analogous to the reaction observed with proteins, the amino groups of DNA bases are also able to react nonenzymatically with reducing sugars. The modifications of DNA by reducing sugars result in the time- and sugar concentration-dependent changes in biological properties. In this communication we review data describing in vitro and in vivo models we have used to investigate the biological consequences of the nonenzymatic glycosylation of DNA. PMID- 2111460 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 23-1990. An 84-year-old man with thickening of the aortic wall, marked fatigue, and a coagulopathy. PMID- 2111461 TI - Cost-effective medical care--real or oxymoron? PMID- 2111462 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 24-1990. A 53-year-old Middle Eastern man with uveitis, hilar lymphadenopathy, and interstitial lung disease. PMID- 2111463 TI - Time-resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis. AB - Crystals of Ha-Ras p21 with caged GTP at the active site have been used to investigate the conformational changes of p21 on GTP hydrolysis. The structure of the short-lived p21.GTP complex was determined by Laue diffraction methods. After GTP hydrolysis, substantial structural changes occur in the parts of the molecule implicated in the interaction with GTPase-activating protein. The trigger for this process seems to be a change in coordination of the active-site Mg2+ ion as a result of loss of the gamma-phosphate of GTP. PMID- 2111464 TI - Migration of myoblasts across basal lamina during skeletal muscle development. AB - Basal lamina is a sheet of extracellular matrix that separates cells into topologically distinct groups during morphogenesis and is thought to form a barrier to cell migration. We have examined whether, during normal muscle development, myoblasts--mononucleate muscle precursor cells--can cross the basal lamina that surrounds each multinucleate muscle fibre. We marked myoblasts in vivo by injecting replication-defective retroviral vectors encoding LacZ into muscle tissue and analysed the fate of their progeny by the expression of beta galactosidase. A dual labelling method with broad application to retroviral lineage-marking studies was developed to ensure that most clusters of labelled cells were clones derived from a single precursor cell. Most of the myoblasts that were infected at a late stage of rat hindlimb development, when each fibre with its satellite myoblasts is individually encased in a basal lamina sheath, gave rise to clones that contributed to several labelled fibres. Our results show that myoblasts from healthy fibres migrate across basal lamina during normal development and could contribute to the repair of fibres damaged by injury or disease. PMID- 2111465 TI - Circular DNA is a product of the immunoglobulin class switch rearrangement. AB - The class of immunoglobulin is defined by the constant region of its heavy chain. When a B lymphocyte switches the class of heavy chain it produces, the constant region of mu-type heavy chain is replaced; this occurs through a DNA rearrangement that brings the gene segment encoding the new constant region close to the VDJ segment encoding the variable region. The pre-B-cell line 18-81, which switches from heavy chain mu to gamma 2b production in culture, occasionally abnormally rearranges the heavy chain locus so that DNA sequences between the switch regions of mu and gamma 2b are inverted. Because looping-out is an intermediate step in generating an inversion, the switch rearrangement could occur by looping-out and deletion. Provided that recombination is reciprocal, this would produce a circle of DNA. Indeed, circular DNA molecules have been isolated as products of rearrangement among gene segments encoding the variable regions of the T-cell receptor and of the immunoglobulin heavy chain and light chain. But whereas the breakpoints for the variable region rearrangement are precisely defined, the breakpoints for any given heavy chain class switch are scattered over a length of greater than 6 kilobases, including both switch regions. We have now isolated circular DNA containing the sequences deleted by class-switching, thereby showing that the immunoglobulin heavy chain class switch occurs through looping-out and deletion. PMID- 2111466 TI - Telomere-telomere recombination provides an express pathway for telomere acquisition. AB - DNA termini from Tetrahymena and Oxytricha, which bear C4A2 and C4A4 repeats respectively, can support telomere formation in Saccharomyces cerevisiae by serving as substrates for the addition of yeast telomeric C1-3A repeats. Previously, we showed that linear plasmids with 108 base pairs of C4A4 DNA (YLp108CA) efficiently acquired telomeres, whereas plasmids containing 28-64 base pairs of C4A4 DNA also promoted telomere formation, but with reduced efficiency. Although many of the C4A4 termini on these plasmids underwent recombination with a C4A2 terminus, the mechanism of telomere-telomere recombination was not established. We now report the sequence of the C4A4 ends from the linear plasmids. The results provide strong evidence for a novel recombination process involving a gene conversion event that requires little homology, occurs at or near the boundary of telomeric and nontelomeric DNA, and resembles the recombination process involved in bacteriophage T4 DNA replication. PMID- 2111468 TI - Oral complications of cancer therapies. Surveillance cultures. AB - Surveillance cultures can be defined as an attempt to take microbiologic inventory, usually for bacteria and fungi, occasionally for viruses, at predetermined times during a patient's clinical course. They are useful in understanding the epidemiology of infection, evaluating techniques of infection prevention, assaying the effectiveness of preventive techniques, and guiding therapeutic decisions when empiric antimicrobial therapy is indicated. As such, they are most frequently used for patients at high risk of infection, such as those with acute leukemia receiving remission induction chemotherapy or bone marrow transplantation therapy. The sites sampled most frequently for surveillance cultures are the nose, oral cavity (pharynx or gingiva), and either the perianum or a stool specimen. Since hospital microbiology laboratories are not designed for the requirements of surveillance culturing, it is essential that such cultures only be obtained following appropriate communication and agreement with the laboratory directors. PMID- 2111467 TI - Sequence homology between a polytene band in the genetic sex chromosomes of Chrysomya rufifacies and the daughterless gene of Drosophila melanogaster. PMID- 2111469 TI - Pretreatment strategies for infection prevention in chemotherapy patients. AB - It is important to understand the pathogenesis of acute oral infections in patients with chemotherapy-induced myelosuppression in order to develop strategies to prevent such complications. Four distinct oral sites that can either be acutely infected or contribute to acute systemic infection are the oral mucosa, dental pulp and periapical tissues, periodontium, and salivary glands. Many cytotoxic drugs can be directly stomatotoxic to replicating oral mucosa. Once mucosal integrity is affected, secondary acute infection can occur. Even without clinical ulceration, deleterious shifts in the oral microbial population can develop. Gram-negative bacilli have been identified as frequent colonizers of myelosuppressed patients, although coagulase-negative staphylococci are being recovered with increasing frequency. Strategies to prevent oral mucosal infection include reducing trauma and preventing proliferation of organisms. Dental pulpal infection is most commonly caused by extensive dental caries. Most pulpal infection is of bacterial origin and can progress to involve the periapical tissues of the involved tooth if not treated. Specific endodontic interventions will usually stabilize or eliminate the source of the infection until the patient's hematologic status returns to normal and definitive pulpal therapy can be provided. In part because acute pulpal complications in the myelosuppressed cancer patient are relatively infrequent, research on the causative organisms and the appropriate therapy of acute, systemic infection of pulpal origin has been limited. Many adults have chronic, asymptomatic periodontal disease. In its advanced stages, extensive ulceration may be present that is not clinically observable. In patients with reduced host defenses, exacerbation of preexistent periodontal disease can have systemic sequelae and is associated with elevated levels of periodontopathic organisms or pathogens typically associated with systemic infection in myelosuppressed cancer patients. Mechanical and chemical antimicrobial techniques are available to reduce prevalence and improve patient comfort and oral hygiene. Dental extractions may be indicated to eliminate the nidus of infection of either pulpal or periodontal origin in patients who are scheduled to receive myelosuppressive chemotherapy. Data indicate that such procedures may be performed without undue risk. Unlike patients who undergo bone marrow transplantation or radiotherapy, patients who receive chemotherapy do not commonly experience subjective salivary gland dysfunction. Occasionally, a transient xerostomia may occur; this condition is frequently attributed to the patient's oral habits, such as breathing through the mouth. The dessicating effect of breathing through the mouth can contribute to oral mucosal injury during function as well as provide a setting for acute infection of commensal origin. More research is needed on the effects of chemotherapy on salivary host defenses. PMID- 2111470 TI - Infection prevention in bone marrow transplantation and radiation patients. AB - This article reviews the prevention of oral and systemic infection in bone marrow transplantation and radiation patients. Prophylaxis of herpes virus reactivation in bone marrow transplant and leukemic patients has resulted in reduced morbidity associated with their medical management. In order to reduce the risk of systemic infection, reduction in ulcerative mucositis is desirable. The use of antifungal and antibacterial agents has not been encouraging to date. Cytoprotective agents have shown some initial success in preventing mucosal breakdown. Further study is required to confirm these initial results. PMID- 2111471 TI - Back to nursing. PMID- 2111472 TI - Education: taking the road ahead. PMID- 2111473 TI - Friend or foe? Hearty handshakes and brutal honesty. Interview by Norah Casey. PMID- 2111474 TI - Berlin: 'Vergessen Sie nicht Rumanien': do not forget Romania. PMID- 2111475 TI - Women in Parliament: balance of power. PMID- 2111477 TI - A strategy for nursing. Developing health care facilities. PMID- 2111476 TI - Psychological effects of breast cancer. PMID- 2111478 TI - Existential psychotherapy. PMID- 2111479 TI - Oxfordshire's health visiting strategy. PMID- 2111480 TI - Pyrexia: what to do about temperatures. PMID- 2111482 TI - Students: why Project 2000? PMID- 2111481 TI - Caring--a hidden value. PMID- 2111483 TI - Against nursing dogmatism. PMID- 2111484 TI - How to deal with patients' relatives. PMID- 2111485 TI - Environment notes: learning through a loophole. PMID- 2111486 TI - Accounting for care. PMID- 2111487 TI - Taxing times. PMID- 2111488 TI - Change and reform: a healthy future. Interview by Norah Casey. PMID- 2111489 TI - Romania: the chains are broken. PMID- 2111490 TI - Equal opportunities. Racism at work. PMID- 2111491 TI - The future of asthma management. PMID- 2111492 TI - The prevention of child sexual abuse. PMID- 2111493 TI - Family planning: evaluating service. PMID- 2111494 TI - A strategy for nursing. Advice for the professionals. PMID- 2111495 TI - HIV and drug users--a three level intervention model. PMID- 2111496 TI - Ignoring the science of ageing. PMID- 2111497 TI - Visiting times: a problem for whom? PMID- 2111498 TI - Students: looking out for your own. PMID- 2111500 TI - Accident and emergency nursing. PMID- 2111499 TI - Growing independents. PMID- 2111501 TI - Accident and emergency nursing. Nurses in the front line. PMID- 2111502 TI - Accident and emergency nursing. A&E nursing: today and the future. PMID- 2111504 TI - Accident and emergency nursing. Advanced trauma life support. PMID- 2111503 TI - Accident and emergency service. Priorities of care. PMID- 2111506 TI - Caring for Romania. PMID- 2111505 TI - Assessing wounds and selecting dressings. PMID- 2111507 TI - Lennox Castle Hospital: in the fast lane .... PMID- 2111508 TI - Life in a Calcutta street clinic. PMID- 2111509 TI - Hydrotherapy: the healing waters. PMID- 2111510 TI - Intravenous infusion pumps. PMID- 2111511 TI - Toxoplasma gondii and toxoplasmosis. PMID- 2111512 TI - Multicultural care: a Jewish perspective on nursing. PMID- 2111513 TI - A strategy for nursing. Targets for staffing and 'manpower'. PMID- 2111514 TI - Touch and go. PMID- 2111516 TI - Primary health care: a new style of health visiting. PMID- 2111515 TI - Sexuality: being out in the open. PMID- 2111517 TI - Primary health care. Parent power. PMID- 2111518 TI - Primary health care. Resource allocation. PMID- 2111519 TI - Primary health care. Abortion: the right choice. PMID- 2111520 TI - Primary health care. Tranx--no thanx. PMID- 2111521 TI - Primary health care. Pervasive uncertainty. PMID- 2111522 TI - Investigation of anti-D antibody dependent cell mediated cytotoxicity in patients with thyroid cancer. AB - Anti-D dependent cellular cytotoxicity (ADCC) of peripheral mononuclear blood cells was measured in 69 thyroid cancer patients belonging to one of the main subtypes, and in 11 age-matched controls with benign thyroid disease. Independently of cancer subtype, tumor status, previous operation, age and sex, no differences in ADCC were observed. Further studies are warranted to clarify the cause of the constant ADCC levels. PMID- 2111523 TI - The role of the left hippocampal region in the acquisition and retention of story content. AB - Thirteen normal control subjects and 62 patients who had undergone either a unilateral temporal or a unilateral frontal lobectomy learned the content of a short prose passage to a strict criterion. Compared to other subject, patients with left temporal-lobe excision took longer to learn the story content and, within this group, the slowest rate noted was for patients with extensive removal from the hippocampal region. When retention of the material was tested after a 20 min delay, only the group with large excisions from the left hippocampus and/or parahippocampal gyrus was impaired. This finding of abnormally rapid forgetting of material learned to criterion highlights the role of the left hippocampal region in the long-term maintenance of verbal information presented in a context. PMID- 2111524 TI - [The role of autoimmune mechanisms in the hyperthyroidism-viral hepatitis syndrome: a possible noncausal association. A review of the literature and the authors' own cases]. AB - Several patients with both Basedow-Graves' hyperthyroidism and viral hepatitis were observed and it was hypothesised that this association could be explained by the individual genetic pattern in which an immunological fragility conditioned a predisposition to autoimmune diseases. This paper reports on the cases observed, the patients' histocompatibility antigen profile and the experimental data found in the literature on autoimmune involvement in the two diseases, whose association may not be coincidental. PMID- 2111525 TI - The impact of prospective payment on the economics, ethics, and quality of nursing. PMID- 2111526 TI - Alternative caregivers: cost-effective utilization of R.N.s. PMID- 2111527 TI - Cost versus quality: in the balance. PMID- 2111528 TI - EDTA chelation as a treatment of arteriosclerosis. PMID- 2111529 TI - Bile acid sequestrants and cholesterol. PMID- 2111530 TI - Prostanoids in the vitreous of diabetic and nondiabetic human eyes with retinal detachment. AB - We measured prostaglandin E2 (PGE2) and prostacyclin levels in the vitreous bodies of 5 eyes of patients with diabetic retinopathy complicated by rhegmatogenous retinal detachment (RRD) and compared them with the corresponding levels in 9 nondiabetic eyes with the same condition as well as with 10 control eyes of deceased patients with no known ocular pathology. We also studied the effect of surgical retinal reattachment on vitreal PGE2 and prostacyclin levels in 4 eyes. Vitreal samples from both nondiabetic and diabetic eyes with RRD were obtained during vitrectomy, while samples from deceased subjects (controls) were obtained 2-6 h after death. Vitreal PGE2 and prostacyclin levels in the control eyes approximated plasma levels (79.9 +/- 20.5 and 124.5 +/- 38.5 pg/ml, means +/ SD, respectively), while RRD in the nondiabetic eyes was associated with increased levels of both PGE2 and prostacyclin (3,170 +/- 3,024 and 467 +/- 283 pg/ml, respectively). In the diabetic eyes with diabetic retinopathy complicated by RRD, all of which underwent retinal photocoagulation, PGE2 and prostacyclin levels were 2-4 times lower than those of the nondiabetic eyes with detached retina. Following surgical retinal reattachment, vitreal levels of both components in diabetics and nondiabetics showed a reduction suggesting that the surgical procedure for obtaining vitreal samples was not the cause for elevated prostaglandin levels in the eyes with detached retina. We showed that RRD is associated with an excessive accumulation of PGE2 and prostacyclin in the vitreous, which is higher in nondiabetic than in diabetic eyes, indicating that diabetic retinopathy in laser-treated eyes might lead to reduced vitreal levels of these metabolites. PMID- 2111531 TI - Changes in the antibacterial activity of melanin-bound drugs. AB - Affinity to melanin and changes of antibacterial activity of melanin-bound drugs were examined in 11 drugs, all of which showed an affinity for melanin. The highest melanin-binding ratio was seen in aminoglycosides. Among these, sisomicin sulfate (SISO) had the highest binding ratio (95.5%). The melanin-binding ratios seen in sulbenicillin sodium (SBPC), cephalosporins and fluoroquinolones were relatively low during the early phase of the reaction, but increased with time. The highest ratio seen in cefazolin sodium was 60.1%. Melanin-bound aminoglycosides showed a reduction in their antibacterial activity with both Bacillus subtilis and Escherichia coli. The reduction rate in the antibacterial activity of melanin-bound SISO against B. subtilis was 50.0% and that against E. coli was 43.0%. No changes in antibacterial activity were seen in the other 6 drugs bound to melanin. PMID- 2111532 TI - Total quality management for physicians: translating the new paradigm. PMID- 2111534 TI - More on motivating medical staff participation in quality assurance. PMID- 2111533 TI - Quality improvement in pharmacy: a prescription for change. AB - Quality improvement activities offer pharmacists opportunities for establishing their roles as clinical practitioners, documenting their contributions to quality of-care improvement, and bringing recognition to pharmacy as a clinical profession. Unfortunately, pharmacists haven't yet recognized the importance of or need for these programs. Drug usage evaluations and quality improvement still are not considered a benefit or an opportunity but continue to be perceived as boring, tedious tasks that must be performed for the Joint Commission rather than the patient. The time has come to refocus our emphasis on what really matters. We need to build quality improvement programs not merely to placate the Joint Commission but to improve the quality of care for patients. We need to build quality improvement programs that extend to the grass roots level of every organization so that everyone is involved, participating, and committed to correcting patient-care problems. This commitment must become a routine habit, a daily acknowledgment, and an ongoing process. Clinical practitioners must become actively involved in quality improvement programs by developing valid, reliable indicators to help ensure safe, appropriate use of drugs. We need to develop a computer model to assist in data collection for drug usage evaluations and quality improvement projects. And we must create a multidisciplinary team of practitioners, including physicians, nurses, and pharmacists, to thoroughly evaluate and respond to this information. A successful team effort means everybody wins, and the biggest winner of all is--and must be--the patient. PMID- 2111535 TI - Institutes of Quality: Prudential's approach to outcomes management for specialty procedures. AB - The Prudential Institutes of Quality program was developed to respond to the growing interest in the quality of care available to patients through both indemnity and managed medical plans and clients' concern about the continued escalation of health care costs. The program is based on the premise that high quality care is the most efficient care that utilizes resources appropriately because of the experience of both the hospital and the physicians. Hospitals and physicians are selected through a questionnaire and site-visit process based on criteria developed from a literature review and outside expert counsel. Networks of facilities meeting the criteria serve the Prudential patient population. The history and results through the third quarter of 1989 and the implications of selective contracting for health care policy are presented. PMID- 2111536 TI - Monitoring and evaluation for coronary artery bypass grafts. AB - Cardiovascular surgeons on the medical staff at Southeast Missouri Hospital, Girardeau, developed indicators, including indications, complications, and outcomes, for the monitoring and evaluation of coronary artery bypass grafts. When the number of sternal wound infections exceeded the threshold for evaluation, action was taken and the occurrence of such infections subsequently declined. PMID- 2111537 TI - A simplified approach to the ambulatory care diagnostic summary list. AB - The Veterans Administration Medical Center at Sepulveda, California, developed a one-page checklist as a "problem summary list." Use of the list has improved legibility of entries, compliance, efficiency, and communication among providers. PMID- 2111538 TI - Medical purchasing guidelines for the business community: how to ask the questions and get the answers we need. PMID- 2111539 TI - [The significance of EEG findings in somnambulism]. AB - In the EEG of 26 patients with somnambulism of an one time transversal examination sharp waves were more frequent than in patients with other diseases, 12 records of 13 children exhibited sharp waves, 5 records of 13 adults, 16 cases exhibited subcortical dysfunctions. There were no relations between epilepsy and somnambulism. Somnambulism was be found preponderantly in episodes of peculiar psychic charge of pupils and young adults. For effective therapy psychological examination is more useful than electrocephalographical examination. The treatment with transquilizer and psychotherapy is rich in meaning. PMID- 2111540 TI - Deficient collagen-induced activation in the newborn platelet. AB - We have investigated the impaired secretion response of neonatal platelets. We compared the response of washed neonatal and adult platelets to thrombin and collagen, and to specific activators of calcium flux (inositol trisphosphate) and protein kinase C activation (oleoyl-acetyl glycerol). Neonatal platelets show no impairment of aggregation, secretion of [14C]serotonin or phosphorylation of specific intracellular proteins in response to thrombin, inositol trisphosphate, or oleoyl-acetyl glycerol. However, neonatal platelets have a markedly decreased response to collagen. To further evaluate this deficient response, we examined specific aspects of the collagen activation pathway. Collagen-platelet interaction as measured by adhesion of platelets to collagen-coated dishes showed no difference in adhesion of neonatal platelets compared to adult controls (20.1 +/- 11.6 versus 18.6 +/- 9.3%). The presence of GPIa/IIa, a Mg2(+)-dependent collagen receptor, was evaluated by flow cytometric analysis of binding of fluorescein-tagged monoclonal antibody, 6F1 (directed against GPIa/IIa). There was no difference either in the percent of platelets that bound antibody (80 versus 81%) or in the mean fluorescence intensity of the adult and neonatal samples. Phosphoinositide hydrolysis was decreased in neonatal platelets in response to collagen but normal in response to thrombin. Neonatal platelets released more arachidonic acid than adult platelets in response to thrombin (29.5 +/- 3.2 versus 19.6 +/- 1.8%) but less than adult platelets in response to 10 micrograms/mL collagen (3.2 +/- 1.1 versus 9.3 +/- 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111541 TI - Group B streptococcus promotes oxygen radical-dependent thromboxane accumulation in young piglets. AB - Both thromboxane A2 and oxygen-derived free radicals appear to play central roles in group B streptococcus (GBS)-induced pulmonary hypertension in piglets. This study tested the hypothesis that GBS promotes oxygen radical-dependent thromboxane accumulation and pulmonary hypertension in infant piglets. Piglets 4 12 d old were anesthetized and prepared for assessment of pulmonary arterial pressure and arterial blood gases. In control animals, GBS (10(8) organisms/kg/min for 15 min) increased mean pulmonary artery pressure by 30 +/- 1.5 torr and reduced arterial PO2 by 100 +/- 20 torr. Thromboxane A2, radioimmunoassayed in venous blood as thromboxane B2, increased by 2452 +/- 800 pg/mL. A second group of piglets was treated with dimethylthiourea (DMTU: 750 mg/kg), a putative oxygen radical scavenger. In these animals, GBS increased pulmonary arterial pressure by only 7 +/- 1 torr and reduced arterial PO2 by a modest 10 +/- 8 torr. Importantly, thromboxane B2 content in venous blood failed to increase above control levels in DMTU-treated animals. The protective effects of DMTU in GBS-treated piglets could not be ascribed to inhibition of cyclooxygenase or thromboxane synthase because the oxygen radical scavenger failed to attenuate increases in pulmonary arterial pressure and venous thromboxane B2 content or reductions in arterial PO2 caused by i.v. infusions of arachidonic acid. DMTU also did not ameliorate pulmonary hypertension evoked by the thromboxane mimetic U44069, thereby suggesting that the scavenger did not act as an end-organ antagonist of thromboxane receptors. These observations suggest that GBS promotes accumulation of thromboxane A2 and attendant pulmonary hypertension through an oxygen radical-dependent mechanism. PMID- 2111542 TI - [Recommendations from the 12th Scandinavian meeting on transfusion medicine]. PMID- 2111543 TI - Diarrhea associated with tube feeding in mechanically ventilated critically ill patients. AB - This study was undertaken to determine the incidence and duration of diarrhea associated with tube feeding in critically ill adult patients who require mechanical ventilation. Of the 73 subjects studied, 63% had diarrhea associated with tube feeding. This incidence is higher than that reported from other studies of critically ill patients who were not mechanically ventilated. Multiple logistic regression analysis revealed that three variables (higher rates of infusion, greater tube-feeding osmolality, and change of tube-feeding product) were statistically significant predictors of diarrhea incidence. Antibiotic use and serum albumin levels were not predictors. In a stepwise multiple regression analysis, the duration of diarrhea was predicted by frequency of diarrhea, within the first 5 days of tube-feeding onset, tube-feeding product osmolality, and rate of tube-feeding infusion. Serum albumin levels and frequency of diarrhea beyond 6 days of tube-feeding onset did not predict duration of diarrhea. Higher osmolality and infusion rates of tube-feeding products did contribute to prediction of both incidence and duration of diarrhea. PMID- 2111545 TI - Parent instruction manual for home parenteral nutrition. PMID- 2111544 TI - Sweeping assumptions away. PMID- 2111546 TI - Prenatal diagnosis of Morquio disease type A using a simple fluorometric enzyme assay. AB - A new fluorogenic substrate, 4 methylumbelliferyl beta-D-6-sulphogalactoside, was used for the assay of galactose-6-sulphate sulphatase activity in chorionic villi, cultured villus cells, and amniocytes. The fluorometric assay is much more convenient than the conventional assay using radiolabelled, sulphated oligosaccharides. Both types of substrate were used in the prenatal diagnosis of three pregnancies at risk for Morquio type A disease using amniocytes. These enzyme tests, as well as electrophoresis of glycosaminoglycans in the amniotic fluid, indicated affected fetuses in two pregnancies and a non-affected fetus in one. PMID- 2111547 TI - Identification of immunoreactive pancreatic stone protein in pancreatic stone, pancreatic tissue, and pancreatic juice. AB - We first examined whether pancreatic stone protein (PSP) was present in pancreatic stone and normal pancreatic tissue. By using HPLC and Western blotting, a protein of Mr 13.5 kDa that reacted with monoclonal antibody against PSP was detected as a major component in EDTA-soluble fractions of pancreatic stone. In an in vitro experiment, this protein dose-dependently suppressed CaCO3 precipitation. PSP was immunohistochemically stained in the acinar cells of normal pancreatic tissue. Based on these findings, it seemed that PSP in pancreatic stone is probably a physiological secretory protein of the pancreas. We subsequently examined immunoreactive PSP in normal pancreatic juice by the Western blotting method. In all of the specimens, the band for immunoreactive PSP in pancreatic juice was found to correspond to 13.5 kDa, which thus agreed with that of purified PSP from a stone. PMID- 2111548 TI - Binding and biological effects of tumor necrosis factor and gamma interferon in human pancreatic carcinoma cells. AB - The cytotoxic/cytostatic effects of recombinant human tumor necrosis factor alpha (rhTNF) and gamma interferon (rhIFN-gamma) were studied in five human pancreatic tumor cell lines. During a 48-h incubation, MIA PaCa-2 cells were most sensitive to rhTNF (56% cytotoxicity, 500 U/ml), T3M4 cells were most sensitive to rhIFN gamma (54% cytostasis, 250 U/ml), and ASPC-1 and COLO 357 cells were most sensitive to the combination of rhTNF and rhIFN-gamma (56 and 55% cytotoxicity, respectively, 250 U/ml of each cytokine). The PANC-1 cells were relatively insensitive to either the individual or the combined effects of these cytokines. All five cell lines exhibited specific, high-affinity receptors for 125I-labeled rhTNF (480-8,610 sites/cell) and rhIFN-gamma (2,050-6,280 sites/cell). The MIA PaCa-2 cells, which were the most sensitive to the inhibitory effects of rhTNF, also possessed the largest number of 125I rhTNF receptors; all other cell lines had a relatively low number of binding sites and low sensitivity. In contrast, no direct correlation could be made between the number of IFN-gamma binding sites and inhibitory sensitivity in any of the cell lines. Incubation of COLO 357 cells at 37 degrees C with either 125I rhTNF or 125I rhINF-gamma led to internalization of the respective 125I-labeled ligand. Our findings document the presence of cytokine receptors in human pancreatic carcinoma cells and suggest that postreceptor events rather than differences in receptor number or affinity more likely govern the responsiveness of pancreatic cancer cells to TNF and IFN-gamma. PMID- 2111549 TI - Efficient expression and Zn(II)-dependent structure of the DNA binding domain of the yeast GAL4 protein. AB - Three protein fragments of different sizes which contain the DNA binding domain of transcription factor GAL4 from Saccharomyces cerevisiae have been expressed in functional forms in Escherichia coli. DNase I footprinting and gel retardation assays showed that the purified proteins bound to the same DNA sequence on the gal1-gal10 promoter as intact GAL4 does. Denaturation--refolding experiments demonstrated that Zn(II) is necessary for maintenance of the conformation of the DNA binding domain of GAL4, as judged on UV-CD and 1H-NMR measurements, as well as for specific DNA binding. PMID- 2111550 TI - The benefits of excellence. A cost-effective treatment programme for pressure sores. AB - This paper evaluates a policy for treating patients with established pressure sores. The results show that excellent nursing care has a significant effect on the rate of healing. PMID- 2111551 TI - Optimization of an assay for studying the effects of agents on cyclooxygenase and lipoxygenase metabolism of arachidonic acid in washed human platelets. AB - Before one can examine the effects of substances on the metabolism of arachidonic acid (AA) by the cyclooxygenase and lipoxygenase pathways, an assay system which allows one to detect increases or decreases in both pathways in needed. In order to develop such a system, we have examined nonaggregating washed human platelets (10(8) platelets/0.5 ml) incubated for various times with 2 microCi 3H-AA and increasing concentrations of AA. T/B2, HHT, 12-HETE, and AA were extracted and separated using reverse phase-HPLC. We first calculated the mass of AA products formed with 10(-7) to 10(-4) M AA and found that the cyclooxygenase was saturated with 10(-5) M AA whereas the lipoxygenase was not saturated with 10(-4) M AA. Cyclooxygenase products were more prevalent than 12-HETE below 10(-5) M AA, while lipoxygenase products predominated at 3 x 10(-5)-10(-4) M AA. Using 3 microM AA, which does not saturate the cyclooxygenase, we examined the effect of 0.25-10 minute incubation durations on the distribution of AA metabolites and found AA product formation to increase throughout this period without completely depleting the substrate. Since substrate depletion does not occur and further metabolism could be detected for both pathways with a 5 minute incubation with 3 microM AA, these incubation parameters were chosen in order to further test the assay system. Using these parameters, we found that 10(-4) M 5-hydroxytryptamine enhanced platelet 12-HETE formation and decreased T/B2 and HHT formation, thus demonstrating the capacity of this system to simultaneously detect changes in cyclooxygenase and lipoxygenase enzyme metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111552 TI - Uptake, distribution and release of 3H-arachidonic acid from human endometrium. AB - The lysophosphatide acyltransferase blocking agent ethylmercurisalicylate (merthiolate) was used to investigate the uptake and release of arachidonic acid from explants of human endometrium in short term tissue culture. Tissue explants were (a) incubated with 3H-arachidonic acid for 1-24 h in the presence or absence of 0.5-50 microM merthiolate, and (b) prelabelled with 3H-arachidonic acid for 18 h followed by incubation with or without 50 microM merthiolate for 1-24 h. Neutral lipids, phospholipids and arachidonic acid were separated by thin layer chromatography and uptake and release of 3H-arachidonic acid expressed as % total uptake. The triglyceride pool was the main target for arachidonic acid uptake. Incorporation increased from 9.1% at 1 h to 56.6% at 24 h. Uptake into phospholipids increased from 8.1% at 1 h to 19.6% at 24 h with phosphatidylcholine accounting for 3.8% and 8.8% respectively. Incubation with 50 microM merthiolate rapidly reduced uptake into triglycerides (to 1.8% at 1 h and 0.9% at 24 h), whereas the effect on uptake into phospholipids (5.9% at 1 h, 3.4% at 24 h) was much less marked. There was a dose related inhibition of arachidonic acid incorporation into both triglycerides and phospholipids, but a lower dose of merthiolate (1 microM) was required to reduce uptake into triglycerides than into phospholipids (5 microM). Uptake into mono- and diglycerides was low and unaffected by merthiolate. Incubation of prelabelled tissue with 50 microM merthiolate resulted in a 20% increase in the release of arachidonic acid from triglycerides and a corresponding accumulation of labelled monoglyceride.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111553 TI - Quantitation of 13-hydroxyoctadecadienoic acid (13-HODE) by radioimmunoassay. AB - Antibodies against 13-hydroxyoctadecadienoic acid (13-HODE) were produced in rabbits by immunizing the animal with 13-HODE-thyroglobulin conjugate. The antibodies appeared to be rather specific for 13-HODE since other hydroxy fatty acids showed minimal crossreaction. The radioimmunoassay was capable of detecting 50 pg per assay tube and was applied to the study of the biosynthesis of 13-HODE in platelets and leukocytes. In contrast to reported findings from endothelial cells, A-23187, thrombin and collagen stimulated synthesis and release of 13-HODE from platelets. However, insignificant synthesis of 13-HODE was found in leukocytes following A-23187 stimulation. Exogenous addition of linoleic acid stimulated the synthesis of 13-HODE from both platelets and leukocytes. The majority of 13-HODE synthesized was found in the medium. These studies suggest that both types of blood cells possess active (omega-6) lipoxygenase. Platelets may use endogenously released linoleic acid to synthesize 13-HODE, whereas leukocytes may utilize linoleic acid released from other cell types for 13-HODE synthesis. PMID- 2111554 TI - Cyclooxygenase products of metabolism of arachidonic acid in mouse macrophages exposed to N-phenyllinoleamide from toxic oil samples. AB - N-phenyllinoleamide (NPLA), one of the major extraneous constituents of Spanish toxic oil samples, appears to enhance the cyclooxygenase metabolic pathway of arachidonic acid by peritoneal mouse macrophages. Results reported herein show an increased biosynthesis of 6-oxo-PGF1 alpha and TXB2 by macrophages exposed to NPLA. However, light and electron microscopy failed to show cellular alterations in macrophages incubated with NPLA for two hours at 27 degrees C. These data suggest a possible involvement of cyclooxygenase arachidonic acid metabolism in the etiopathogenesis of the Spanish Toxic Oil Syndrome. PMID- 2111556 TI - Longitudinal and cross-sectional studies of the relationship between 6-keto PGF1 alpha and high density lipoproteins. AB - Two studies were performed to examine the relationship between Prostacyclin (PGI2) and high density lipoprotein cholesterol (HDL-C). A longitudinal study examined the stable metabolite of PGI2, 6-keto PGF1 alpha, along with HDL-C, and total cholesterol (TC) before (Week 0), during (Week 4), and after (Week 9) an eight week aerobic conditioning program. 6-keto PGF1 alpha was measured by radioimmunoassay using 125I, and HDL-C and TC were spectrophotometrically analysed. Maximal oxygen uptake and resting heart rate data obtained at Week 0 confirmed that the training group (E) was not different from the sedentary group (C). Results obtained at Week 9 indicated that maximal oxygen uptake was higher (p less than 0.05) and resting heart rate lower (p less than 0.05) in the E group, while these variables remained unchanged in group C. Levels of 6-keto PGF1 alpha, HDL-C, and TC did not differ between groups E and C when Week 0 was compared with Week 9. However, within the E group, significantly lower concentrations of 6-keto PGF1 alpha (p less than 0.05) and HDL-C (p less than 0.05) were found at Week 4 compared with Week 0. A cross-sectional study involving 52 subjects examined the relationship between 6-keto PGF1 alpha and several cardiovascular disease risk factors which included HDL-C. The only significant correlation (r = 0.50 p less than 0.05) observed was between 6-keto PGF1 alpha and HDL-C. PMID- 2111555 TI - Pulmonary hypertensive response to foreign body microemboli. AB - Pulmonary hypertension and foreign body granulomas are recognized sequelae of chronic intravenous drug abuse. We have recently described the development of transient pulmonary hypertension and increased permeability pulmonary edema after the intravenous injection of crushed, suspended pentazocine tablets in both humans and dogs. To determine the role of vasoactive substances in the development of this transient pulmonary hypertension, we measured pulmonary hemodynamics and accumulation of arachidonic acid metabolites in dogs during the infusion of indomethacin, a cyclooxygenase inhibitor, diethylcarbamazine (DEC), a lipoxygenase inhibitor, and FPL 55712, a receptor antagonist for leukotriene C4/D4 (LTC4/D4). Following the intravenous administration of crushed, suspended pentazocine tablets (3-4 mg/kg of body weight), mean pulmonary artery pressure increased from 14 +/- 2 mmHg to 30 +/- 6 mmHg (p less than 0.05) at 60 secs with a concomitant increase in plasma concentrations of 6-keto-PGF1 alpha from 187 +/- 92 pg/ml to 732 +/- 104 pg/ml and thromboxane B2 from 206 +/- 83 pg/ml to 1362 +/ 117 pg/ml (both p less than 0.05). Indomethacin prevented the increase in both cyclooxygenase metabolites, but had no effect on the pulmonary hypertension. In contrast, DEC had no effect on the increase in cyclooxygenase products, but blocked the pulmonary hypertension. FPL 55712 did not effect either the increase in cyclooxygenase metabolites or the pulmonary hypertension. We conclude that the transient pulmonary hypertension, induced by the intravenous injection of crushed, suspended pentazocine tablets, is not mediated by cyclooxygenase products but may be mediated by lipoxygenase product(s) other than LTC4/D4. PMID- 2111557 TI - Psychoanalysis and character development. PMID- 2111559 TI - Emily Dickinson: the interweaving of poetry and personality. PMID- 2111558 TI - Female fetishes and female perversions: Hermine Hug-Hellmuth's "a case of female foot or more properly boot fetishism" reconsidered. PMID- 2111560 TI - Erotized transference reconsidered: expanding the countertransference dimension. AB - A reconsideration of the erotized transference from a contemporary perspective has been presented utilizing detailed case material provided by Stoller. The main thesis is that this type of transference, traditionally conceived as a product of a particular kind of patient often felt to be borderline, is better understood as arising in a specific intersubjective context involving both participants in the psychoanalytic situation. The focus is on the intricate interaction of analyst and patient, recognizing that either may serve as a selfobject for the other. This view assumes a more expanded countertransference role than recognized in the earlier literature. The psychoanalytic situation can be erotized by either or both participants. A corollary thesis is that the details of a patient's fantasy should also be viewed as codetermined and that imbedded within it might be the patient's subjective experience of the psychoanalytic interaction. Alluded to peripherally is that the erotized transference in the interaction between male analyst and female patient is, in part, a manifestation of traditional roles assumed in situations involving a male authority figure in close engagement with a female who perceives herself as relatively powerless. This issue has recently received considerable attention from writers who have addressed themselves to the important gender issues in psychoanalysis. PMID- 2111561 TI - A training analysis for psychoanalytic psychotherapists. AB - For historical reasons, psychoanalytic psychotherapy has been regarded as a second-class treatment in comparison with psychoanalysis, and standards for training in it have lagged behind those for psychoanalysis. However, psychoanalytic psychotherapy is the treatment of choice for many healthier (or higher-level) patients who cannot receive analysis for any reason, and also for a large population of more-disturbed patients who are not appropriate for psychoanalysis. Mastering techniques of psychoanalytic psychotherapy may be as difficult as mastering those of psychoanalysis, and should require comparable theoretical training, supervision, and personal treatment. This "development lag" in the training of psychoanalytic psychotherapists has taken place for several reasons: (1) Psychoanalytic ideas first emerged in America in the context of a new movement toward an electric, but dynamic psychiatry from which psychoanalysis had to establish its separate identity. (2) Psychotherapy was associated with techniques of suggestion and manipulation from which psychoanalysis wished to separate. (3) Because psychotherapy was seen as an inferior form of therapy which required little training, institutes were slow in being established, and reluctant to require a "training analysis." It is suggested that with the full training of psychoanalytic psychotherapists, this discipline may be regarded as a profession comparable to psychoanalysis. It is further suggested that the optimal treatment for the full training of the psychoanalytic psychotherapist is psychoanalysis, and that a "training psychotherapy" is not an adequate substitute, but may provide a transitional step to resolve initial resistances and to prepare the therapist for a training analysis. PMID- 2111562 TI - A psychoanalyst takes the Turing Test. PMID- 2111563 TI - Beyond the future of an illusion: further reflections on Freud and religion. PMID- 2111564 TI - Reel significations: an anatomy of psychoanalytic film criticism. PMID- 2111565 TI - [The reaction of tumors and normal tissues to therapy with fast neutrons from the U-120 cyclotron]. AB - In the present information results of clinical studies are represented to show the effectiveness of therapy with 6.3 MeV fast neutrons in 45 patients with superficial tumors in head and neck area. The reaction of tumor and of normal tissue was studied in dependence on different physical and biological factors. Two variants of neutron therapy planning were estimated by means of mathematical models of a factor of time-dose-fractionation for neutron (TDFN) from clinical point of view. Results of changes in oxygen-tension within the tumor are represented in 20 patients with metastases in cervical lymph-nodes during neutron therapy. The obtained data show a correlation of regression and reoxygenation rate of the tumor to its initial volume. The reaction of the tumor in therapy with fast neutrons was studied in dependence on its morphological structure. Complete regression of epidermoid and nonepidermoid cancer types was seen in 42 or 89% of the cases. With corrections for adipose tissue and the extent of dose fraction of fast neutrons the clinical test of the mathematical model of TDFN factor made discernible that the reaction of normal tissue can be prognosticated quite exactly by means of this model in neutron therapy. PMID- 2111566 TI - [Enteral tube feeding using Cosilat in the complex therapy of patients with late radiation injuries of the colon]. AB - Results are presented applying an enteral nutrition by means of probes with Cosilat in complex therapy of patients with radiotherapeutic late effects of the colon. This nutrition was prescribed with the intention to gave the colon a functional recovery and to guarantee optimal conditions for repair of radiation injuries. Good results were seen in 27 of 28 patients (96.7%), the situation of one patient (3.3%) continued without any change. Cosilat has a high nutritive value, good organoleptic qualities and is digested well. In use complications did not appear. PMID- 2111567 TI - [Contrast echography of uterine tumors using albumin-carbon dioxide-foam]. AB - A method of contrast echography with albumin-carbon dioxide foam is reported. 140 women aged 20 to 60 were investigated. By filling the uterine cavity and in some cases the tubes the sagittal and longitudinal size of the uterus were determined and tumourous nodes in the uterine well were demonstrated. Contrast echography significantly widens the scope of ultrasonography of the uterus and its adnexa. PMID- 2111568 TI - Reversible and irreversible injury in the reperfused myocardium: differentiation with contrast material-enhanced MR imaging. AB - Thrombolytic agents are being used with increasing frequency to produce reperfusion of acute myocardial infarction in humans. This study was designed to assess the potential of a magnetic resonance (MR) contrast agent, the manganese chelate of N,N'-bis(pyridoxal-5-phosphate) ethylenediamine-N,N'-diacetic acid (DPDP), in differentiating between reversible and irreversible myocardial injury during reperfusion. Ischemia was produced in rats by occlusion of the left coronary artery for either 15 minutes (n = 10) or 2 hours (n = 10), followed in both cases by 30 minutes of reperfusion. Signal intensity (SI) was measured before and after (every 15 minutes for 1 hour) the administration of Mn-DPDP. Prior to intravenous injection of the contrast agent, no significant difference in SI was observed between normal and reversibly or irreversibly injured myocardium. Mn-DPDP produced greater enhancement of SI of the irreversibly injured region compared with normal myocardium. There was no differential enhancement of the reversibly injured region compared with normal myocardium. Thus, Mn-DPDP is useful in discriminating reversible from irreversible injury in reperfused myocardium. PMID- 2111569 TI - Spinal cord compression due to ossification of ligaments: MR imaging. AB - A total of 108 patients with ossification of the posterior longitudinal ligament (OPLL) (n = 92), ossification of the yellow ligament (OYL) (n = 8), or both (n = 8) were examined with magnetic resonance (MR) imaging performed with 0.5-T superconductive and 0.22-T resistive units. OPLL was demonstrated as a low-signal intensity band between the bone marrow of the vertebral body and the dural sac on T1- and T2-weighted images. Continuous cervical OPLL was easier to diagnose than segmental cervical OPLL. T2-weighted images were more useful for detection of ossification of the ligaments. OYL was recognized as an impression on the posterior dural sac. Formation of bone marrow within an area of ossification, shown as increased or intermediate signal intensity, was observed in 56% of the cases of continuous OPLL, 11% of the cases of segmental OPLL, and none of the cases of OYL. The degree of cord compression was more severe in continuous OPLL. Degeneration of the disk was frequently associated with both types of OPLL. PMID- 2111570 TI - Regulation of prostaglandin E2 synthesis in human amnion by protein kinase C. AB - A role for protein kinase C (PKC) in mediation of prostaglandin E2 synthesis in human amnion cells has been suggested. We have investigated the specificity of the stimulation of PGE2 synthesis by phorbol esters and employed putative PKC inhibitors to demonstrate the specificity of PKC stimulation. The three phorbol esters, tetradecanoyl phorbol-13-acetate, phorbol-12,13-dibutyrate and phorbol 12,13-didecanoate gave concentration-dependent (10(-10)-10(-7)M) increases in PGE2 synthesis when added to amnion cells in monolayer, however, no effect was seen with the structurally similar phorbols phorbol-12-13-diacetate, 4 alpha phorbol-12-13-didecanoate or phorbol base. The stimulatory effect of TPA (10( 8)M) on amnion PGE2 synthesis could be prevented by coincubation with the putative protein kinase C inhibitors 1-(5-isoquinoline sulphonyl) piperazine, 1-0 octadecyl-2-0-methyl-rac-glycero-3-phosphocholine, sphingosine and chlopromazine at concentrations of 10(-6)-10(-4)M. Addition of the transcription inhibitor actinomycin D at 10(-6)-10(-5)M prevented TPA (10(-8)M)-induced PGE2 synthesis. However, paradoxically, a further increase in PGE2 synthesis was seen when 10(-9) 10(-7)M actinomycin D was added together with TPA. The phospholipase A2 inhibitor quinacrine was able to prevent the TPA-induced increase in PGE2 synthesis even in the presence of exogenous arachidonic acid suggesting that phospholipase A2 may be a target for PKC action. PMID- 2111571 TI - Prostaglandins in human semen during fish oil ingestion: evidence for in vivo cyclooxygenase inhibition and appearance of novel trienoic compounds. AB - Marine oils may offer cardiovascular benefits, but inhibition of prostaglandin E and prostaglandin F synthesis by fish oil has been found in animal studies, and such effects could alter physiological responses in man to a clinically significant degree. Since greater amounts of E and F-type prostaglandins are made in human seminal vesicles than in the rest of the body combined, the influence of n-3 supplements upon semen prostaglandins was assessed in 10 subjects before and after one month of taking 50 ml menhaden oil daily. Prostaglandins E1, E2 and their 19-hydroxy derivatives were measured by HPLC-UV as PGB's, and prostaglandin E3, 19-OH PGE3, and analogous PGF's by gas chromatography/mass spectrometry. Fish oil ingestion reduced concentrations of one- and two series prostaglandins (mean reduction in PGE's = 37%, in PGF's = 20%, p less than 0.05), while more than doubling the low amounts of PGE3 and PGF3 alpha, and their previously undescribed 19-hydroxy derivatives. Semen phospholipids were enriched in eicosapentaenoic acid after dietary fish oil, but sperm counts and motility were not altered during the study. Since dietary fish oil reduces prostaglandin concentration in semen, clinical trials of n-3 fatty acids should also evaluate other possible results of in vivo cyclooxygenase inhibition. PMID- 2111572 TI - Temporal changes in metabolites of prostanoids in milk of heifers after intramammary infusion of Escherichia coli organisms. AB - A study was conducted to characterize the changes in the concentrations of three metabolites of prostanoids in the milk of a) heifers (n = 14; control) inoculated with Escherichia coli (E. coli) organisms into the udder and b) in heifers (n = 10; treatment) vaccinated with E. coli bacterin and treated similar to control heifers. Milk samples were obtained from the challenged quarter and analyzed for the concentrations of stable metabolites of thromboxane A2 (TXB2), prostacyclin (PCM) and prostaglandin E2 (PGEM) using radioimmunoassays. In control heifers milk TXB2 concentrations were significantly higher (P = 0.03) compared to treated heifers. Milk PCM concentrations increased significantly (P = 0.02) in control and treated heifers after the respective treatments, however, differences between the two groups were not significant. Milk PGEM concentrations also increased significantly (P = 0.02) in control and treated heifers after the respective treatments, and there were no differences between the two groups. Results of the present study suggest that, the prostanoids have a role in the pathophysiologic process of coliform mastitis. PMID- 2111573 TI - A gas chromatographic assay for tocainide carbamoyl-O-beta-D glucuronide:quantitation of the base hydrolyzed product, 3-(2',6'-xylyl)-5 methylhydantoin. AB - Quantitation of tocainide carbamoyl-O-B-D-glucuronide, a major metabolite of the antiarrhythmic agent, tocainide, was previously reported using sodium hydroxide hydrolysis (pH greater than 12) of the glucuronide followed by gas chromatographic analysis of the hydrolyzed product, 3-(2',6'-xylyl)-5 methylhydantoin. In this investigation, the hydantoin was found to undergo rapid degradation during base hydrolysis of the tocainide glucuronide. The hydantoin was synthesized and its hydrolysis in sodium hydroxide (pH greater than 12) was found to follow first-order kinetics with an estimated half-life of 24.6 minutes. This spontaneous and rapid degradation of the hydantoin during hydrolysis of the tocainide glucuronide may result in underestimation of the hydantoin. To correct for the degradation of the hydantoin, a gas chromatographic assay with a timed, base-hydrolysis calibration protocol was designed. To demonstrate the applicability of this assay, the elimination kinetics of tocainide and the tocainide carbamoyl glucuronide were studied in three healthy male volunteers after a single 200 mg oral dose of tocainide hydrochloride. From urine data, the elimination half-life of tocainide was approximately 15.5 hours. The urinary excretion half-life of the tocainide carbamoyl glucuronide was approximately 13.8 hours. PMID- 2111574 TI - [From the evaluation of health programs]. PMID- 2111575 TI - [Cytokines and rheumatoid polyarthritis]. AB - Cytokines play a role in the chronicity of inflammation, the formation of lesions and the persistence of the immune response observed in rheumatoid arthritis (RA). The dysregulation of the cytokines observed in RA is of great immunopathological importance. There is an increase in the macrophage-derived cytokines such as interleukin 1, the tumor necrosis factor alpha and interleukin 6. At the same time, there is a decrease in the lymphocyte-derived cytokines such as interleukin 2, interferon gamma and interleukin 4. Certain growth factors (transforming growth factor beta, platelet derived growth factor, granulocyte macrophage-colony stimulating factor) also play a role in RA. The study of the role of these various cytokines in the formation and maintenance of articular and extra articular lesions in RA is carried out. PMID- 2111576 TI - Prevention of enamel demineralization adjacent to glass ionomer filling materials. AB - In order to study the release of fluoride and prevention of enamel demineralization by different filling materials, standardized cavities were prepared in 80 extracted human molars. The cavities were filled as follows: 1. Fuji II F; 2. Ketac-Fil; 3. Ketac-Silver; 4. Silar. Twenty molars were used as controls (no filling). Enamel slabs with the fillings were subjected to 9 days of demineralization (30 min daily) and remineralization (artificial saliva, replaced daily). Fluoride release in the saliva was determined on days 1, 3, 5, and 9. Enamel fluoride content adjacent to the cavities was determined initially and after the de-remineralization using the acid etch technique. On day 1, the largest amount of fluoride in the saliva was released by Fuji, but on day 9 the largest amount was released by Ketac-Fil. Ketac-Silver released significantly less fluoride than Fuji and Ketac-Fil. The average initial fluoride content of enamel was 2200 ppm. After the test period, fluoride contents adjusted for biopsy depth were 1822, 1690, 1693, 1337, and 888 ppm in groups 1-5, respectively. The amounts of phosphorus dissolved by the second acid etch were 28.9 (SE 2.6), 30.2 (2.0), 34.4 (2.8), 44.1 (2.7), and 42.2 (2.4) micrograms, respectively. Softening of surface enamel during the test period was clearly reduced in teeth filled with Fuji and Ketac-Fil. The results show that glass ionomer materials release considerable amounts of fluoride and prevent demineralization of the adjacent enamel in vitro. Fuji and Ketac-Fil seem to be more effective than Ketac-Silver. PMID- 2111577 TI - Short- and long-term fluoride release from glass ionomers and other fluoride containing filling materials in vitro. AB - Test specimens of seven different glass ionomer filling materials and one fissure sealant were exposed to running water for 2 yr. One amalgam and one composite, both containing fluoride, were included for comparison. The fluoride release from the specimens was measured periodically after storing the specimens for 24 h or 1 wk in a small amount of water. The fluoride release from the glass ionomers decreased with time and a constant level was reached for most products during the 2-yr period. The release was increased by lowering the pH of the storage solution. The release from the glass ionomers was clearly greater than from the amalgam and the composite. PMID- 2111578 TI - Structural motif of the GCN4 DNA binding domain characterized by affinity cleaving. AB - The NH2-terminal locations of a dimer containing the DNA binding domain of the yeast transcriptional activator GCN4 have been mapped on the binding sites 5' CTGACTAAT-3' and 5'-ATGACTCTT-3'. Affinity cleaving was effected by synthetic GCN4 proteins with Fe.EDTA moieties at the NH2-terminus. Analysis of the DNA cleavage patterns for dimers of the Fe.EDTA-proteins corresponding to GCN4 residues 222 to 281 and 226 to 281 revealed that the NH2-termini were in the major groove nine to ten base pairs apart and were symmetrically displaced four to five base pairs from the central C of the recognition site. This result is consistent with the Y-shaped scissor grip-leucine zipper model recently proposed for a class of DNA binding proteins important in the regulation of gene expression. PMID- 2111579 TI - Relation of neuronal APP-751/APP-695 mRNA ratio and neuritic plaque density in Alzheimer's disease. AB - An ongoing controversy concerns the cellular distribution of the differentially spliced forms of the amyloid protein precursor (APP) mRNAs and changes in prevalence of these transcripts during Alzheimer's disease. In situ hybridization on serial sections was used to prove that most hippocampal pyramidal neurons contain both APP-751 and APP-695 mRNA species. The APP-751/APP-695 mRNA ratio is generally increased during Alzheimer's disease, as shown by RNA gel blot analysis. Moreover, there was a strong linear relation between the increase in APP-751/APP-695 mRNA ratio in pyramidal neurons and the density of senile plaques within the hippocampus and entorhinal cortex. Thus, the increase in APP-751/APP 695 mRNA provides a molecular marker for regional variations in plaque density between individuals diagnosed with Alzheimer's disease by the commonly used composite criteria. PMID- 2111580 TI - A novel nucleoprotein complex at a replication origin. AB - The viral protein p6, required for the protein-primed initiation of replication of Bacillus subtilis phage phi 29, forms a nucleoprotein complex at the viral replication origins that shows novel features. Deoxyribonuclease I and hydroxyl radical footprinting data, as well as the induction of positive supercoiling, support a model in which a DNA right-handed superhelix tightly wraps around a multimeric p6 core. The interaction occurs through the DNA minor groove. The activity of p6 not only requires the formation of the complex but also its correct positioning, indicating that the other proteins involved in the initiation of replication recognize, at a precise position, either the p6 core or the DNA conformational change induced by p6. PMID- 2111581 TI - A new redox cofactor in eukaryotic enzymes: 6-hydroxydopa at the active site of bovine serum amine oxidase. AB - An active site, cofactor-containing peptide has been obtained in high yield from bovine serum amine oxidase. Sequencing of this pentapeptide indicates: Leu-Asn-X Asp-Tyr. Analysis of the peptide by mass spectrometry, ultraviolet-visible spectroscopy, and proton nuclear magnetic resonance leads to the identification of X as 6-hydroxydopa. This result indicates that, contrary to previous proposals, pyrroloquinoline quinone is not the active site cofactor in mammalian copper amine oxidases. Although 6-hydroxydopa has been implicated in neurotoxicity, the data presented suggest that this compound has a functional role at an enzyme active site. PMID- 2111582 TI - Deciphering Alzheimer's disease: the amyloid precursor protein yields new clues. PMID- 2111583 TI - Cleavage of amyloid beta peptide during constitutive processing of its precursor. AB - The amyloid beta peptide (A beta P) is a small fragment of the much larger, broadly distributed amyloid precursor protein (APP). Abundant A beta P deposition in the brains of patients with Alzheimer's disease suggests that altered APP processing may represent a key pathogenic event. Direct protein structural analyses showed that constitutive processing in human embryonic kidney 293 cells cleaves APP in the interior of the A beta P, thus preventing A beta P deposition. A deficiency of this processing event may ultimately prove to be the etiological event in Alzheimer's disease that gives rise to senile plaque formation. PMID- 2111584 TI - Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. AB - An amyloid protein that precipitates in the cerebral vessel walls of Dutch patients with hereditary cerebral hemorrhage with amyloidosis is similar to the amyloid protein in vessel walls and senile plaques in brains of patients with Alzheimer's disease, Down syndrome, and sporadic cerebral amyloid angiopathy. Cloning and sequencing of the two exons that encode the amyloid protein from two patients with this amyloidosis revealed a cytosine-to-guanine transversion, a mutation that caused a single amino acid substitution (glutamine instead of glutamic acid) at position 22 of the amyloid protein. The mutation may account for the deposition of this amyloid protein in the cerebral vessel walls of these patients, leading to cerebral hemorrhages and premature death. PMID- 2111585 TI - Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein. AB - An inhibitor of coagulation factor XIa was purified from serum-free conditioned medium of HepG2 liver cells. Platelets stimulated with thrombin or calcium ionophore (A23187) secrete a protein functionally and immunologically identical to the inhibitor, implying a role for this inhibitor in hemostasis. Analysis of the amino-terminal amino acid sequence and immunologic reactivity showed the inhibitor to be a truncated form of the Alzheimer's amyloid precursor protein that contains a Kunitz-type serine protease inhibitor domain and at least a portion of the amyloid beta protein. It inhibits factor XIa and trypsin with a Ki of 450 +/- 50 pM and 20 +/- 10 pM, respectively. Heparin (1 unit/ml) did not significantly effect inhibition of trypsin, but inhibition of XIa was 15 times greater (Ki = 25 +/- 15 pM) in the presence of heparin. PMID- 2111586 TI - Hepatic abscess after biliary tract procedures. AB - Seven patients with hepatic abscess that developed after prior operation upon the biliary tract were treated during a two year period. In contrast with the fulminant clinical presentation of hepatic abscess usually associated with acute obstructive suppurative cholangitis, the presentation of hepatic abscess after prior biliary tract procedures was surprisingly indolent; several patients had been treated with oral antibiotics for several weeks or months with the presumptive diagnosis of nonsuppurative cholangitis. Thorough investigation of the entire biliary tree was necessary to identify associated biliary disease, which included biliary-enteric anastomotic stricture, intrahepatic stricture, excluded sectoral bile duct from iatrogenic injury and reflux of abnormally contaminated intestinal contents. Extensive reconstructions of the biliary tract were performed upon three patients. Recurrence of the abscess occurred once after percutaneous and once after surgical drainage and was managed by drainage of the associated excluded sectoral bile duct or fistulojejunostomy. Operative drainage of hepatic abscess after prior biliary operation may be preferable to percutaneous techniques to provide definitive surgical management of associated pathologic findings of the biliary tract. PMID- 2111587 TI - Viscoelastic substances in ophthalmology. AB - The desirable properties of a viscoelastic substance for ophthalmologic applications are intimately tied to its chemical and rheologic properties. This report describes the relevant rheologic properties (e.g., viscosity, viscoelasticity, pseudoplasticity, cohesiveness, and coatability) of the available viscoelastic substances and presents the general principles of their use as well as some specific technical aspects. In addition, the various uses of viscoelastic substances in ophthalmic surgery are outlined. There is no single ideal substance for all circumstances. With a knowledge of the rheologic properties of each substance, the ophthalmologist will be able to choose among the different ones as necessary to suit each clinical situation. PMID- 2111589 TI - Insulin, cortisol and catecholamines do not regulate circadian variations in fibrinolytic activity. AB - To evaluate possible hormonal regulators of the diurnal rhythm in fibrinolytic activity, we measured tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor activity (PAI-1), t-PA antigen, insulin, cortisol, and catecholamines in 6 healthy males (age 34 +/- 5) every 2 hours for 24 hours. Fibrinolysis was characterized by a peak in PAI-1 activity and a trough in t-PA activity at 0600 h. PAI-1 activity increased 92% and t-PA activity decreased 56% between 2400 h and 0600 h. t-PA antigen (principally a measure of t-PA/PAI-1 complex), peaked at 0800 h. In comparison, insulin levels were lowest at night when PAI-1 activity was rising. The weak inverse correlation between insulin and PAI-1 activity (r = -0.28, p less than 0.02), was not sufficient to explain the diurnal change in fibrinolysis. While cortisol demonstrated the expected circadian change, the increase in cortisol did not occur until 0400 h, 4-6 hours after the rise in PAI-1 and decrease in t-PA activity started. Supine resting plasma epinephrine and norepinephrine showed no circadian rhythm. From this data, we hypothesize that the increased level of PAI-1 in the morning consumes t-PA, leading to decreased t-PA activity and increased t-PA/PAI-1 complex. Further, we conclude that insulin, cortisol, and catecholamines are not responsible for the circadian rhythm of fibrinolysis. PMID- 2111588 TI - Pargyline-sensitive selective accumulation of a radiolabeled MPTP analog in the primate cerebral cortex and basal ganglia. AB - The distribution of radioiodinated N-methyl-4-(4-hydroxy-3-iodobenzyl)-1,2,3,6 tetrahydropyridine (MHTP), an analog of the reportedly nontoxic N-methyl-4-benzyl 1,2,3,6-tetrahydropyridine, (4-homo-MPTP), has been studied in the primate. [123I]MHTP-derived radioactivity exhibited a progressive accumulation and prolonged retention within the primate eye. Following iv injection, [123I]MHTP rapidly accumulated within the primate brain and was subsequently oxidized to a radiolabeled metabolite. The half-life of [123I]MHTP-derived radioactivity within the primate brain was 50 min. The highest concentrations of radioactivity were found in the caudate-putamen and the frontal, temporal and cingulate cortices; the substantia nigra and inferior olivary nucleus were labeled with medium intensity. Very low concentrations of radiolabel were detected in the cerebellum and white matter. Selective accumulation of [125I]MHTP-derived radioactivity within these structures was blocked by pretreatment with pargyline, suggesting that monoamine oxidase B is involved in the bioactivation of radioiodinated MHTP. PMID- 2111590 TI - Modulation of vein wall prostacyclin synthesis by cultured human malignant melanoma cells. PMID- 2111591 TI - Differential expression and regulation of the human CD8 alpha and CD8 beta chains. AB - The CD8 glycoprotein is expressed by thymocytes, mature T cells and natural killer (NK) cells and has been implicated in the recognition of monomorphic determinants on major histocompatibility complex (MHC) Class I antigens, and in signal transduction during the course of T-cell activation. Both human and rodent CD8 antigens are comprised of two distinct polypeptide chains, alpha and beta. The majority of monoclonal antibodies (mAb) reactive with the human CD8 antigen bind the CD8 alpha chain, while a single mAb, T8/2T8-5H7, has been identified which binds to the CD8 alpha/beta heterodimer. While the two chains of CD8 have been presumed to be coordinately expressed in normal T cells, this is not always the case. Northern blot analysis of a panel of T-cell leukemias and normal cells demonstrate that CD8 alpha and CD8 beta are not invariably co-transcribed and phenotypic analysis of fresh and interleukin 2 (IL-2) expanded peripheral blood mononuclear cells (PBMC) confirm that the CD8 alpha and CD8 beta chains are differentially expressed at the cell surface. Four distinct subpopulations of CD8+ cells have been identified based on the expression of CD8 alpha/alpha or CD8 alpha/beta complexes: (1) T-cell receptor (TcR) alpha beta+ T cells which are CD8 alpha+/beta+; (2) TcR alpha beta+ T cells which are CD8 alpha+/beta-; (3) TcR gamma delta+ T cells which are CD8 alpha+/beta- and (4) natural killer (NK) cells which are CD8 alpha+/beta-. We also demonstrate the down-regulation of the CD8 alpha/beta heterodimers from the surface of a CD8+ T-cell clone following treatment with phorbol myristate acetate (PMA) while CD8 alpha/alpha homodimers remain on the cell surface. This observation demonstrates that a) a CD8+ T-cell clone can express both CD8 alpha/alpha homodimers and CD8 alpha/beta heterodimers and b) these two complexes do not have identical biological properties. Together, these data suggest that CD8 alpha/alpha and CD8 alpha/beta dimers may not subserve identical functions. The differential contribution of these two CD8 complexes should be considered in models of T-cell-mediated cytotoxicity and T cell activation. PMID- 2111592 TI - New targets for drug action: is high selectivity always beneficial? PMID- 2111593 TI - [Meningococcal disease: are patients carriers of meningococci after treatment with antibiotics?]. AB - The aim of the study was to determine whether patients treated for meningococcal disease carried meningococci in the throat on discharge from hospital. If this were the case, supplementary treatment with e.g. rifampicin would be appropriate. The study comprised 106 patients: 98 patients in whom meningococci had been isolated from cerebrospinal fluid, blood or petechiae and eight patients with clinical signs of meningococcal disease in whom meningococci had been isolated only from tracheal aspirate or throat specimens. In 35% (22/62), meningococci were isolated from throat specimens on admission to hospital. From 20 throat specimens inoculated on 5% horse blood agar only, one meningococcal isolate was recovered (5%). From further 37 specimens inoculated on chocolate agar medium selective for pathogenic Neisseria, 18 meningococcal isolates were recovered (49%). This difference is statistically significant (p = 0.001). Meningococci were not isolated from any throat specimens taken on discharge from hospital; 90% (47/52) of these specimens were examined using selective chocolate agar medium. From an observed carriage rate of zero out of 47 it can be judged that the carrier rate does not exceed 6.4% (95% confidence limit). From these results, we conclude that it is unlikely that patients, who have been treated for meningococcal disease, are the source of infection in secondary cases. PMID- 2111594 TI - [Long-term respirator treatment]. AB - Long-term respirator treatment in the patients' own home is instituted increasingly frequently in patients with neuromuscular diseases. Positive pressure ventilation via a permanent tracheostomy is employed. Treatment is frequently commenced electively during hospitalization in particularly interested departments. Discharge to the patients' home is undertaken after thorough instruction of the patient himself, the family and the persons who help the patient with his other daily needs. Possible guidelines for establishing this form of treatment are outlined on the basis of literature from abroad. PMID- 2111595 TI - Is BSE simply scrapie in cattle? PMID- 2111596 TI - Algal poisoning. PMID- 2111597 TI - Sarcoptic mite hypersensitivity: a cause of dermatitis in fattening pigs at slaughter. AB - The prevalence of Sarcoptes scabiei in pigs in the Netherlands, and the causal relationship between infestation and dermatitis in fattening pigs were assessed in a survey in 1988. In the first part of the survey 400 fattening pigs from 88 farms and 200 sows were examined. In the second part of the survey 193 fattening pigs with normal skin and 201 with dermatitis were examined; the dermatitis was characterised by small round, slightly thickened skin lesions, mostly on the rump, flanks, abdomen and buttocks. Ear scrapings were collected from all the animals after slaughter and examined for the presence of sarcoptic mites. In the first part of the survey, 33 (8.25 per cent) of the 400 fattening pigs and nine (4.5 per cent) of the 200 sows were positive for S scabiei. Mange was detected in fattening pigs from 21 (23.9 per cent) of the 88 farms. In the second part of the survey, six (3.1 per cent) of the 193 fattening pigs with normal skin and 30 (14.9 per cent) of the 201 pigs with dermatitis were positive for S scabiei. This difference was statistically significant (P less than 0.001). Histological examination of the skin lesions revealed an eosinophilic perivasculitis compatible with an allergic reaction, and consistent with infestation with S scabiei. The results of this survey indicate that mange is common in the Netherlands, and that sarcoptic mite hypersensitivity can be a cause of the skin lesions seen in fattening pigs at slaughter. PMID- 2111599 TI - Interaction between Eimeria uzura infection and aflatoxicosis in Japanese quail (Coturnix coturnix japonica). AB - The clinical signs and gross lesions caused by Eimeria uzura (10(5) oocysts) in Japanese quail (Coturnix coturnix japonica) exhibited little or no influence in the face of intercurrent dietary aflatoxicosis (1 p.p.m. of aflatoxin B1 from Day 0 to 55). Similarly, no significant differences in the mucosal morphology of the intestine were evident histologically between the two groups of Japanese quail. The nervous signs of ataxia, leg weakness, incoordination of movement, torticollis and terminal opisthotonos were toxin-induced manifestations. In the aflatoxic quail, hypoplastic changes and selective depletion of lymphocytes were more prominent in the bursa of fabricius. Increased relative mean weights of liver, kidney, spleen, crop, proventriculus and gizzard were observed in birds due to aflatoxin sensitivity. The combination of E. uzura infection and aflatoxicosis in Japanese quail may cause significant weight loss, and increased oocyst production and reproductive potential. PMID- 2111598 TI - Treatment of experimentally induced cytauxzoonosis in cats with parvaquone and buparvaquone. AB - The efficacy of parvaquone (Clexon) and buparvaquone (Butalex) in treating experimentally induced feline cytauxzoonosis was explored. Domestic cats were inoculated subcutaneously with blood from a cat infected with Cytauxzoon felis and treated daily with either 20 or 30 mg kg-1 parvaquone, or 5 or 10 mg kg-1 buparvaquone, beginning on either the first day parasites were detected in peripheral blood, or 2 days after the onset of parasitemia. Fifteen cats were treated and all but one died due to the infection. Unexpectedly, one of two non treated, infected control cats survived. Although parvaquone and buparvaquone are the treatments of choice for a related hemoprotozoan parasite causing theileriosis in African cattle, wer concluded that at the dosages and regimes tested, these drugs are not effective treatments for feline cytauxzoonosis. Blood from the two surviving cats was inoculated into naive cats and in these animals clinical disease or death were not observed. The latter two naive recipient cats were then inoculated with a lethal dose of viable, frozen C. felis and both died, thereby indicating that blood from surviving cats did not induce an infectious state that resulted in immunity. The two cats that survived the acute infection were subsequently challenged with a lethal inoculum of C. felis; they showed no clinical signs of cytauxzoonosis and were obviously immune to reinfection. PMID- 2111600 TI - [Deoxyribonuclease from Corynebacterium diphtheriae: dynamics of synthesis and properties]. AB - Diphtheritic bacteria of PW-8 Massachusetts strain produced into cultural medium only one nucleotidase--endoDNAase. The enzyme was synthesized by the cells during the exponential phase of growth. The DNAase was purified 500-fold and exhibited properties specific to neutral-alkaline DNAases (pH optimum about 7.5, absolute requirements for Me2+, single-step mechanism of substrate hydrolysis). The following properties were typical for the enzyme: absence of distinct specificity to structure of bases surrounding the hydrolyzed bond, formation of 5'-end phosphate groups and slightly higher preference to denatured DNA. PMID- 2111601 TI - [The effect of alimentary hypercholesterolemia on the level of lipids and essential fatty acids in rabbit enterohepatic circulation]. AB - Patterns of lipid metabolism were estimated in biological fluids and tissues involved in enterohepatic circulation of bile lipid complexes in female rabbits with alimentary hypercholesterolemia. Cholesterol gallstones were not found in gallbladder of rabbits with alimentary hypercholesterolemia. A number of reasons was responsible for the phenomenon, including specific ratio of four lipid components, which contributed to maintaining bile cholesterol in soluble form: concentration of bile acids was unaltered simultaneously with high contents of cholesterol and a decrease in phospholipids level, while content of free fatty acids was increased and the content of arachidonic acid was elevated in majority of lipid fractions. PMID- 2111602 TI - [The effect of monovalent cations on the activity of site-specific endonuclease PaeII]. AB - Activity of restrictase Pae II, contrary to known restriction enzymes of the II class (except of true isoshizomere Sma), depended absolutely on monovalent cations. This pattern is untypical for restrictases of the II class. At the same time, restrictase Pae II was able to hydrolyze DNA as a substrate in absence of exogenous Mg2+, in the incubation mixture contained cations K+, Rb+, Cs+ and NH4+ but not Na+ or Li+. Mg2+ was found to activate the enzyme in presence of monovalent cations. Basing on the protective effect on K+ against inactivation of restrictase Pae II by means of thiol-affecting reagents and high temperature as well as on stabilization of the enzyme by KCl during storage, monovalent cations appear to participate in formation of protein molecule structure, which is optimal for catalytic effect and resistant to inactivation. PMID- 2111603 TI - [Studies on ultraweak luminescence of bacteria]. AB - Ultraweak luminescence of Escherichia coli, Bacillus subtilis and Brevibacterium ammoniagenes was measured with high sensitive single photon counting equipment (Made in China). The results obtained from ultraweak luminescence of as above three bacterial strains were as follows: spectral distribution curves, photon emission kinetic curves or emission intensity and its qualitative relationship between intensity and bacterial counts. PMID- 2111604 TI - [Study on the discrimination of bacteria by gas chromatographic profiles of cellular monosaccharides]. AB - A procedure for obtaining gas chromatographic (GC) profiles of bacterial cellular monosaccharides was described. Some of the unknown component peaks in these profiles were identified. And, based on the complete linkage cluster analysis with the Euclidean distance coefficient, the interpretation of the resulting cellular monosaccharides of bacteria were performed by mini-computer. By means of this method, the discrimination of 5 species (24 strains) of aerobic endospore forming bacteria. The results showed that there were defined differences between the profiles of cellular monosaccharides of B. anthracis and B. cereus. This procedure has provided a useful method for the classification and identification of microorganisms, for their physiological and biochemical studies, and for studies on their subcellular components. PMID- 2111605 TI - Epilepsy surgery in children. AB - Epilepsy surgery is becoming an increasingly used therapy for children with severe, medically intractable seizures. Temporal lobe ablation, corpus callosotomy, and hemispherectomy are currently the most commonly performed procedures. In this review the presurgical evaluation of patients with medically intractable seizures is described and risks and benefits of the surgery discussed. In selected patients temporal lobectomies and hemispherectomies may totally eliminate seizures while corpus callosotomies frequently reduce number and severity of generalized seizures. PMID- 2111606 TI - [Focal epilepsy: generation and spreading mechanisms in experimental conditions]. AB - This paper describes essential mechanisms underlying focal epileptic activity. Within the centre of an epileptic focus neurons display a characteristic phenomenon - the paroxysmal depolarization shift. This type of activity is partly caused by membrane-intrinsic mechanisms and also by postsynaptic excitation. Burster neurons seem to play a special role in this mechanism. Whereas the centre of an epileptic focus is distinguished by its massive excitation, the immediate surrounding are characterized by massive inhibitory phenomena ("epileptic inhibition"). The transition from interictal to ictal phenomena goes along with the spread of activity to adjacent neocortical areas. Experimental studies give strong evidence that this epileptic spread is dependent on neocortical anatomy. PMID- 2111607 TI - [Benign Rolandic epilepsy in children. Topographic EEG analysis]. AB - Topographic EEG investigation with instant voltage mapping showed maximal negativity of "Rolandic" spikes over central or midtemporal electrodes with spread to parietal or upper frontal areas with a dipol formation (centro-temporal negativity, frontal positivity). Spike amplitude or duration was not correlated with spread to adjacent areas. No other focal abnormalities, such as focal slowing, occurred. Spike activity was pronounced during light sleep and was often associated with generalized spike wave activity, which is more likely to be a sign of functional disturbance rather than the sequelae of brain damage. A review of literature shows that this pattern is helpful in the differentiation from focal abnormalities due to brain lesions. PMID- 2111608 TI - [Computerized tomography in epilepsy in children]. AB - We present a retrospective study of 160 children attending our epilepsy out patient department. Computed tomography (CT) was performed on 123 (77%) patients, namely all children with the exception of those with febrile seizures, typical absence seizures, and benign Rolandic epilepsy. Incidence of CT abnormalities and their correlation with clinical features were evaluated. The CT scan was normal in 84 and abnormal in 39 patients. Although in general, the detection of abnormality on CT will not alter the management of the child, in a small percentage (2%) of our cases a lesion treatable by surgery was discovered. The indications for CT are summarized. PMID- 2111609 TI - [Function and structure of families with an epileptic child]. AB - Although the impact of psycho-social factors on the individual patient with epilepsy has been widely investigated, the influence of the illness on the family as a whole is still underestimated. By means of the Family Assessment Measure (FAM III), a well-validated instrument, we investigated which measurable influence the epilepsy of one child had on the functioning of the families. Data from a group of 72 families with a child suffering from epilepsy (EG), but without any other handicap were analysed and compared with those of 75 families with a child with severe mental retardation (SMG) and 76 control families (CG). Data were gathered through home visits. Only complete families were studied. Results showed that the EG was similar to the SMG in all 3 scales of FAM III, but differed significantly from the CG. In 26% of the families in EG and in 19% of the SMG clear signs of family malfunctioning were found, as compared with 6.5% of the CG. Family disfunctioning in EG was of a greater variety that in SMG. We found that within the EG the type of seizures (41 patients with generalized tonic clonic fits, 10 with complex partial seizures and 21 with absences) did not have any impact on the results. In addition, neither the duration of the illness nor the absolute length of seizure-free periods seemed to matter. Only families who had the subjective feeling that their children were still suffering from epilepsy showed significantly higher rates of family malfunctioning. Summarizing, we found that epilepsy in a child can have a severe impact, not only on his individual life and on the mother-child relationship, but on the functioning of his family as the whole. This fact should be taken into account in the treatment of these children and should influence family counselling, as well. PMID- 2111610 TI - [Neuroimmunologic parameters in therapy refractory epilepsy in children]. AB - In a prospective study comprising 48 children (21 boys, 27 girls, age 12 months to 15 years) the hypothesis was tested whether an alteration in the light chain immunoglobulins kappa (kappa) and lambda (lambda) is an expression of autoimmune mechanisms and could be used as a diagnostic parameter. Immunoglobulins were analysed by kinetic nephelometry. The patients were grouped according to clinical and laboratory parameters. A high kappa/lambda ratio caused by high concentration of the kappa chain was found in children with therapy-resistant epilepsy. 60% showed a high kappa/lambda ratio, no distinct association was ascertainable in 26% cases and in 14% of the cases false positive results were obtained. In seizure-free children immunological markers were specific in 72% of cases, whilst 24% could not be characterized and 4% showed false positive results. The kappa/lambda ratio, therefore, is a good diagnostic aid in the treatment of therapy-resistant epilepsies. PMID- 2111611 TI - [Intravenous immunoglobulin in the treatment of malignant epilepsy in children]. AB - 15 children with malignant epilepsy showing no response to conventional antiepileptic drugs or hormone therapy were administered intravenous immunoglobulin (Endobulin, Immuno) at a dosage of 400 mg/kg per day on the 1st and 15th day and subsequently every three weeks for 6 months. 7 of these 15 patients showed IgG2 subclass deficiency. A significant reduction in attacks, or even absence of attacks was observed in 10 out of 15 children after six months of intravenous immunoglobulin therapy. Apart from one patient with ringchromosomopathy, all the children with IgG2 subclass deficiency responded to this therapy. The reduction of attacks after i.v. immunoglobulin therapy correlates with the improvement or normalization of the EEG findings. At present, the authors consider the number of patients still too small to make a final assessment, but they believe that intravenous immunoglobulin holds an important position in the treatment of malignant epilepsy in childhood. PMID- 2111612 TI - [The startle response and epilepsy]. AB - Startle responses (SR) are described as epileptic and non-epileptic attacks and their mechanisms are poorly understood. Long-loop reflexes and a satisfactory response to L-tryptophan treatment have only seldom been published in this condition. This prompted us to report a case with epilepsy and startle-induced tonic spasms, the latter refractory to all conventional medication except for L tryptophan. Special emphasis is placed on the electrophysiological findings. Similar observations of non-habituation of SR in post-anoxic brain damage and in the case of startle epilepsy possibly suggest a deficit of cortical inhibition, probably in the supplementary motor area, rather than brain stem dysfunction in both instances. PMID- 2111613 TI - Glycogen effects on energy state and passive electric properties of liver during protection. AB - In order to evaluate the importance of glycogen for the hepatic tolerance to ischemia, livers of swine fed a glucose-potassium solution for premedication were perfused with either Bretschneider's HTK-solution (histidine-tryptophan ketoglutarate) or with Euro-Collins-solution (EC) prior to subsequent ischemia at 25 and 5 degrees C. During ischemia, in regular intervals or continuously, energy rich phosphates, lactate, intrahepatic pH and the electrical impedance of liver tissue were determined. The results were compared with corresponding data from swine which had starved for 48 h. Corresponding to the higher glycogen content, energy supply during ischemia was markedly improved by the premedication. Despite high amounts of glucose in the EC-solution, energy supply after glucose-potassium premedication was no better with EC-solution than with HTK-solution. Moreover, glucose uptake led to concomitant cellular water uptake. Electrical impedance measurements during ischemia mirrored improved energetical protection by the glucose-potassium premedication. PMID- 2111614 TI - [Hemodynamic adaptation during extracorporeal perfusion and arteriovenous extracorporeal CO2 removal]. AB - During an animal study using five bastard dogs the hemodynamic relations during extracorporeal perfusion with an arteriovenous circuit and extracorporeal CO2 removal (ECCO2-R) were analyzed. We utilised a prototype circuit (Promed, West Germany) which is by diminution and using silicon rubber adapted to the application in newborn. A silicon lung (Scimed, 0.8 m2, ECCO2-R) was used in the circuit. During the six hours perfusion period a main arterial blood pressure of 83 +/- 17 mmHg and an extracorporeal blood flow of 412 +/- 56 ml/min was found using arteriovenous perfusion via the femoral artery and vein. We found a statistical significant correlation (r = 0.66) between the main arterial blood pressure and the extracorporeal blood flow. Further more there was a significant correlation between the arterial PCO2 and the blood flow through membrane lung (r = 0.81). In conclusion our animal experiments approved the possibility of hemodynamic adaptation to an arteriovenous circuit as well as effectiveness of CO2 removal via such circuit. PMID- 2111615 TI - [Osteosis and calcinosis in scleroderma circumscripta linearis]. AB - In a female patient suffering from linear morphea of long duration, we observed ossification and calcification of the affected tissue. There were no other abnormalities that might have been responsible for these symptoms. PMID- 2111616 TI - Severe ischemia of the hand following intra-arterial promazine injection: effects of vasodilation, anticoagulation, and local thrombolysis with tissue-type plasminogen activator. AB - Promazine hydrochloride was injected accidentally in the antecubital artery of a 42-year-old woman, resulting in severe ischemia of the second and third fingers of her right hand which lasted for four days before she was hospitalized. Vasodilation by combining axillary plexus block and intravenous sodium nitroprusside did not improve ischemia and local thrombolysis was performed using recombinant tissue-type plasminogen activator (50 mg over 8 hours), resulting in normalization of digital pressure in one of the two affected fingers. The outcome was favourable and amputation could be avoided. PMID- 2111617 TI - [Atopic dermatitis. IV. The role of proteinase inhibitors in the pathogenesis, assessment of the severity and the prognosis of the disease]. AB - Examinations of 59 patients with atopic dermatitis have revealed increased content of the major inhibitors of proteinases, a relationship between the patients' age and alpha 2-macroglobulin level in both the patients and the reference group normal subjects. Detection of correlations between alpha 1 proteinase inhibitor and serum IgE as well as between C1 inactivator and C3c have lead to a supposition on the contribution of proteinase inhibitors in the modulation of immune reactions. Clinical features of atopic dermatitis in alpha 1 proteinase inhibitor deficiency and in various blood serum IgE levels are discussed. PMID- 2111618 TI - [Experience in treating patients with microsporosis of the smooth skin with involvement of the lanugo hair]. AB - Seventy-four patients with smooth skin microsporosis with involvement of the lanugo were treated with a 10% quinosol solution in dimexid. The foci were smeared twice a day. Resolution of the clinical manifestations and elimination of the fungi were achieved in 5-14 days, in 9.4 days on an average. This therapeutic method does not involve manual epilation and oral griseofulvin, no side effects were recorded. PMID- 2111619 TI - [Acute Lipschutz-Chapin vulvar ulcer]. AB - A 17-year-old female patient is described, who had a sexual intercourse, the only in her life, a year before. Hectic temperature has developed in the presence of an exacerbation of chronic decompensated tonsillitis; the general status has essentially deteriorated. A sharply painful ulcer, up to 2 cm in diameter, was seen on the lower third of the involved labium majus; Lactobacilli casei were isolated from the discharge from this ulcer. After 2 weeks of antibiotic and immunocorrective therapy a delicate atrophic cicatrix has formed. The factors that helped diagnose the Lipschutz-Chapin acute vulvar ulcer were exacerbation of a chronic focal infection, anemia, leucocytosis, thrombocytopenia, dysproteinemia, and disordered cellular and humoral immunity. PMID- 2111620 TI - [The regulating action of oxygen on the nutritional requirements of Neisseria meningitidis]. AB - The study has revealed regularities in changing nutritional requirements of Neisseria meningitidis with changes in the degree of the oxygen saturation of the culture medium in a fermenter under the conditions of the controlled cultivation of N. meningitidis in a synthetic culture medium in the process of batch, semicontinuous and continuous flow cultivation. As shown in this study, when oxygen supply is limited, the consumption of carbohydrates prevails, while in the presence of surplus oxygen the prevalence of the consumption of amino nitrogen is observed. PMID- 2111621 TI - [Serological and epidemiological characteristics of acute pneumonias caused by Mycoplasma pneumoniae in Belgorod]. AB - The etiology of the outbreaks of acute pneumonia in Belgorod was established and their epidemiological features were studied. The mycoplasmal etiology of all cases of acute pneumonia in children and adults, appearing alongside acute respiratory infections resulting from the preceding outbreaks caused by influenza viruses A/Prague/, B/Leningrad/369/75, and all types of parainfluenza viruses, was shown. The droplet mechanism of the transfer of infection was established, which was confirmed by the severity of the outbreak and a high rate of infection of the medical staff at hospitals for children and adults, where patients with mycoplasma-induced pneumonia were treated. PMID- 2111622 TI - [The modelling of a Pseudomonas aeruginosa wound process]. AB - P. aeruginosa wound infection was induced in white mice to test new preparations against P. aeruginosa. This model ensures the nearest approximation to the course of P. aeruginosa chronic infection, i.e. it reproduces the focus of inflammation and the prolonged course of the disease (the positive decision on application No. 4, 324, 555 of November 2, 1987, has been obtained). The essence of the method consists in obtaining the model of P. aeruginosa wound infection by a combined trauma of the skin (burn and incision): P. aeruginosa is introduced in a dose of 6 X 10(9)-8 X 10(9) microbial cells into the burn blister through the incision made 3 hours after the burn and then 20-24 hours later in a dose of 10(9)-2 X 10(9) microbial cells, introduced under the crust formed by that time. PMID- 2111623 TI - [The outer membrane proteins of Neisseria meningitidis: the outlook for their use in developing preparations for immunoprophylaxis]. PMID- 2111624 TI - Morphologic and immunocytochemical evaluation of 220 fine needle aspirates of malignant lymphoma and lymphoid hyperplasia. AB - A total of 220 fine needle aspiration (FNA) specimens from 212 patients with clinically suspected or previously histologically confirmed lymphoma were evaluated by cytology in conjunction with immunophenotyping analysis of the aspirate; the results were compared with the histologic diagnosis made on previous or current accessions of lymph node or extranodal tissue. Smears of the aspirates were stained with the Diff-Quik and Papanicolaou stains while immunoperoxidase staining using antibodies against kappa and lambda immunoglobulin light chains and Leu-4 was routinely performed on Cytospin preparations. Where indicated, additional marker studies (including T-200, Leu-1, Leu-2a, Leu-3a + 3b, Leu-M1, B1, Leu-12, IgM, CALLA and TdT) were performed. For the non-Hodgkin's lymphomas, specimens were classified by the cytologic characteristics of the neoplastic cells according to the International Working Formulation scheme. The combination of cytologic smears and immunoperoxidase studies resulted in a diagnosis of lymphoma in 173 cases (79%). The remaining aspirates were interpreted as suspicious for lymphoma (7%), benign (10%) or inadequate for diagnosis (4%). Of the 15 suspicious aspirates, 5 proved to be Hodgkin's disease and 2 to be T-cell lymphoma by subsequent biopsy. The cause of failure in the nine inadequate aspirates were necrosis (3 cases), sclerosis (2 cases) and faulty technique (4 cases). In the cases that had concurrent tissue biopsies, no false-positive diagnoses were rendered. These results indicate that FNA used in association with immunocytochemistry is a reliable tool for establishing the diagnosis and classification of the majority of cases of lymphoma. Optimal immunoglobulin light-chain ratios for defining monoclonality in FNA specimens of B-cell lymphomas are proposed. PMID- 2111625 TI - Cervical screening revisited. AB - Some of the achievements of cervical screening in the reduction of morbidity and mortality in different countries are briefly reviewed, along with a consideration of some of the aspects of cervical cancer screening programs. The latter include the organization of the program (e.g., whether it is organized by the national health authorities), the protection afforded by routine screening, the assurance of quality in cervical sampling and in the screening program, the screening interval, the age groups to be screened, the compliance of women to present themselves for screening and of health care personnel to provide appropriate follow-up and/or treatment for the lesions diagnosed, the problem of false positives and its relation to overdiagnosis and overtreatment and, finally, the cost effectiveness. It is concluded that a centrally organized and well supervised cervical screening program, cautiously executed and with all involved parties closely cooperating, can be a cost-effective means of combatting cervical cancer. PMID- 2111626 TI - Cost-effective services in cytology. PMID- 2111627 TI - Influence of perioperative nalbuphine and fentanyl on postoperative respiration and analgesia. AB - In a double-blind study the relative postoperative respiratory and analgesic effects of perioperatively administered nalbuphine and fentanyl were compared in 60 females undergoing gynecological surgery under i.v. anesthesia. One milliliter (10 mg) nalbuphine was considered equipotent to 1 ml (100 micrograms) fentanyl. In the recovery period pain was assessed by visual analog score (VAS) and recovery by Pegboard scoring. Respiratory function was evaluated by continuous monitoring of respiratory frequency and end-tidal CO2 (ETCO2) and by frequent arterial blood gas analyses. The total volume of analgesic required for surgical analgesia was similar in the two groups. Patients in the nalbuphine group showed mild to moderate increases in pulse rate during the intubation phase and in blood pressure during surgery. Fentanyl was more effective in suppressing these cardiovascular responses. Within the first 15 min following recovery, increasing PaCO2 and ETCO2 as well as respiratory rates below 10/min were noted in 8 patients, who all belonged to the fentanyl group; in 4 of these patients i.v. naloxone had to be administered to reverse respiratory depression. Prolonged sedation was a common feature in patients receiving nalbuphine. It was concluded that fentanyl was superior to nalbuphine in attenuating the pressor responses to intubation and surgery. However, fentanyl was associated with respiratory depression in a considerable number of patients. The quality and duration of postoperative analgesia were similar in the two groups. PMID- 2111629 TI - Predictable PaCO2 with two different flow settings using the Mapleson D system. AB - Two different settings of fresh gas flow (VFG) and minute ventilation (VE) used with the coaxial Mapleson D system (Bain), were evaluated in 59 adults (ASA I III) during controlled ventilation and different types of surgical procedures. The two flow settings (alternatives A and B) were VFG of 75 and 110 ml.min-1.kg-1 and VE of 150 and 175 ml.min-1.kg-1, aiming to generate normocapnea and mild hypocapnea, respectively. The PaCO2 obtained with alternative A was 5.5 +/- 0.5 kPa (mean +/- s.d.), with 92% of the patients within the range 4.7-6.1 kPa. With alternative B, the PaCO2 was 4.4 +/- 0.5 kPa, with 82% of the patients within the range 3.5-4.9 kPa. It is concluded that these two flow regimes are suitable for clinical use when either normocapnea or mild hypocapnea is desired. PMID- 2111628 TI - Lung lavage and surfactant replacement for hydrochloric acid aspiration in rabbits. AB - Hydrochloric acid (0.1 N, 5.0 ml.kg-1 in total) was administered intratracheally to 28 adult rabbits anesthetized with pentobarbital and mechanically ventilated with pure oxygen. When the PaO2 decreased to 14.1 +/- 2.8 kPa (mean +/- s.d.), the PaCO2 increased to 8.9 +/- 2.5 kPa, and the minute ventilation (VE) decreased to 51 +/- 8% of the baseline value, animals were divided into 4 groups. The deteriorated values did not improve in the non-treated (control) animals, whereas the animals treated with lung lavage and surfactant replacement showed a significant increase in PaO2 to 35.1 +/- 12.2 kPa, and maintained lower PaCO2 and larger VE than the controls. These parameters showed no significant improvement with surfactant replacement alone, and deteriorated further with lung lavage alone. The minimum surface tension (gamma min) of the edema fluid that accumulated in the airways after acid administration was 22.5 +/- 1.7 mN.m-1, and was not lowered by adding surfactant preparation (10 mg.ml-1) whose original gamma min was less than 2 mN.m-1. We concluded that surfactant inhibition by edema fluid was a cause of respiratory failure, and that lung lavage followed by surfactant replacement might be of therapeutic value for acid aspiration. PMID- 2111630 TI - Predicted normocapnea in infants and children using the Bain circuit with controlled ventilation. AB - We have constructed a nomogram for fresh gas flow (VFG) and minute ventilation (VE) for paediatric anaesthesia during controlled ventilation using the Bain coaxial Mapleson D circuit. VFG was based upon the assumption of a high fresh gas utilization because of a low VFG/VE ratio (0.67) and known figures of carbon dioxide elimination. The formulas VFG = 27.8 x VCO2 and VE = 1.5 x VFG were used to calculate the necessary flows to generate normocapnea. The nomogram was evaluated in 59 children (6-62 kg, age 5 months-14 years). PaCO2 (mean +/- s.d.) was 5.0 +/- 0.5 kPa (38 +/- 4 mmHg) with a total range of 3.9-6.3 kPa (29-47 mmHg). Ninety percent of the children had a PaCO2 of 5.7 kPa (43 mmHg) or lower. There was no correlation between body weight and PaCO2. Hence, there was no difference in mean values between children below or above a body weight of 20 kg. PMID- 2111631 TI - Quantification of oral epithelial hyperplasia in rats after topical application of the carcinogen 4-nitroquinoline 1-oxide. AB - Hyperplasia of the palatal epithelium was quantified in two groups of rats exposed thrice weekly to the carcinogen 4NQO for 2 weeks and 2 months, respectively. The lengths and areas of the epithelial layers were measured with a computerized line-following device. In the group treated for 2 weeks the maximum area of the nuclear layer was nearly three times and the maximum length of the epithelial/connective tissue interface almost twice the normal at the end of the carcinogen application period. The maximum area of the cornified layer was three times and the maximum lengths of the epithelial surface and the keratin/nuclear layer interface almost one and a half times the normal 1 week after painting with 4NQO. Thereafter the lengths and areas decreased gradually in both experimental groups. The area of the cornified layer and the length of the epithelial/connective tissue interface in the group treated for 2 months were significantly larger than those in animals treated for 2 weeks. These variables may be two of several indicators of prognostic significance in the assessment of dose-related premalignant epithelial hyperplasia. PMID- 2111632 TI - Prospective study of EDTA clearance among patients in long-term lithium treatment. AB - EDTA clearance as a measure of the glomerular filtration rate was followed up to 10 years in 14 patients in long-term lithium treatment. The results in the lithium-treated patients were identical to the results in a standard population. PMID- 2111633 TI - Magnetic resonance imaging in clinical psychiatry. AB - Although psychiatric researchers have been quick to adopt magnetic resonance imaging (MRI) of the brain in their investigations, its clinical application has been slow to develop and most psychiatrists remain unaware of its potential advantages and disadvantages compared with CT scanning. In this article the procedures are compared and the potential advantages of MRI highlighted with the help of neuropsychiatric case histories. Clinical situations are then discussed in which a psychiatrist should consider ordering a MRI scan subsequent to or instead of a CT scan. PMID- 2111634 TI - Immunoenhancement in wasting protein-energy malnutrition: assessment of present information and proposal of a new concept. PMID- 2111635 TI - Glomerulonephritis with organized deposits: a new clinicopathological entity? Light-, electron-microscopic and immunofluorescence study of 12 cases. AB - Twelve cases of glomerulonephritis in patients without systemic diseases, displaying organized glomerular deposits, were reported. Microfibrils (11-30 nm diameter) were found in 9 patients and microtubules (20-35 nm diameter) in the other 3. Histochemical stainings for amyloid were always negative. By light microscopy, mesangial proliferative, membranous and membranoproliferative patterns were seen in 5, 3 and 4 patients, respectively. By immunofluorescence, granular deposits, mainly of IgG and C3, were found in all cases, either in the mesangium or in the mesangium and in the capillary walls. A second biopsy was performed in 2 patients. The number of hyaline glomeruli was increased, but the general pattern of glomerular changes remained unchanged. The commonest clinical findings were hypertension, microhematuria and proteinuria, often of nephrotic range. At variance to what is reported in the literature, 2 pediatric cases were found as well, and the overall prognosis (mean follow-up 54.3 months) was mostly favorable. The diagnostic relevance of these findings is pointed out, but further investigations are needed, before suggesting a new clinicopathological entity. PMID- 2111636 TI - Mesangial immunoglobulin A deposits in minimal change nephrotic syndrome: a report of an older patient and review of the literature. AB - A 57-year-old patient with a history of monoclonal immunoglobulin A (IgA) gammopathy developed idiopathic nephrotic syndrome. Renal biopsy showed minimal glomerular changes with predominant glomerular mesangial IgA. The association of glomerular mesangial IgA with otherwise typical minimal change nephrotic syndrome has been noted before, and the literature concerning this combination of findings is reviewed. The patient herein described represents one of the two oldest patients yet reported with this syndrome and raises questions about the relationship between minimal change disease and IgA nephropathy. Severe proteinuria (and even the nephrotic syndrome) is not necessarily the harbinger of a poor prognosis in IgA nephropathy if the glomerular morphology is otherwise consistent with minimal change nephrotic syndrome. Such patients should be treated in a fashion similar to those with minimal change nephrotic syndrome. The significance of the IgA gammopathy in the pathogenesis of this case is unknown. PMID- 2111637 TI - Managed care, managed people, and community mental health. PMID- 2111638 TI - Capitation payment systems and public mental health care: implications for psychotherapy with the seriously mentally ill. AB - The evolution, rationale, and implications of capitation payment systems in public mental health are discussed. These systems will unify the clinical, administrative, and fiscal structures of state and community mental health providers. Psychotherapeutic practice may shift to more action-oriented, problem focused, brief and crisis interventions. The diminishing prospects for long-term intensive psychotherapy and the need to demonstrate its clinical efficacy and economic feasibility are discussed. PMID- 2111639 TI - Response to 35% CO2 as a marker of panic in severe anxiety. AB - One inhalation of 35% CO2 was administered to each of 32 patients with high anxiety ratings. Only patients with panic disorder had increases in reported anxiety upon CO2 intake. CO2-triggered anxiety appears specific for panic disorder and independent of baseline anxiety. PMID- 2111640 TI - Molecular analysis of the Rett syndrome using cDNA synapsin I as a probe. AB - A cDNA encoding for rat synapsin I, a neuron-specific protein localized on the cytoplasmic surface of synaptic vesicles and probably involved in the regulation of neurotransmitter release from nerve terminals, has been used to map the human gene to the short arm of the X chromosome. We have screened, using this cDNA, the DNAs of six unrelated girls with the Rett Syndrome (RS) to test the hypothesis that mutations of the human synapsin I gene might cause RS. We found no alterations at the synapsin I (Syn I) locus in the vicinity of the probe sequence. PMID- 2111641 TI - Site-directed mutagenesis by complementary-strand synthesis using a closing oligonucleotide and double-stranded DNA templates. AB - An approach for generating structures capable of directing full-length complementary-strand synthesis for double-stranded plasmid DNA is described. The structures are formed following heat denaturation and cooling of linearized plasmid DNA molecules in the presence of what is referred to as a "closing" oligonucleotide. Consisting of a sequence complementary to the free ends of one of the two plasmid strands, the closing oligonucleotide functions as an agent for recircularization of a DNA strand and generation of a primer-circular template structure suitable for polymerase-dependent full-length complementary-strand synthesis and ligation into a covalently closed heteroduplex molecule. When combined with a mutagenic oligonucleotide and uracil-substituted DNA templates, this approach allows site-directed mutagenesis to be performed directly on double stranded DNA with a mutant formation efficiency of about 50%, a level amenable to rapid screening by DNA sequencing. PMID- 2111642 TI - The use of multiple mass spectral line pairs for enhanced precision in isotope enrichment studies of 15N-labeled amino acids. AB - A method for enhancing the precision in the calculation of isotope enrichment for 15N-labeled amino acids is presented. The method utilizes multiple line pairs for the calculation of isotope enrichment. Using multiple line pairs allows the evaluation of calibration curves for nonlinear behavior and permits differentiation among sites containing more than one labeled nitrogen. The increase in precision is related to the number of isotopically shifted line pairs used in calculating the isotopic enrichment and varies with the amino acid of interest. PMID- 2111643 TI - UDP-glucuronyltransferase activity toward harmol in human liver and human fetal liver cells in culture. AB - This paper presents a fast HPLC assay for measuring UDP-glucuronyltransferase (UDPGT) activity in extracts of adult human liver and human fetal liver cells in culture. Harmol glucuronide formed was quantitated directly without prior hydrolysis after a simple step of selective extraction of harmol. The method is applicable to crude liver homogenates as well as to partially fractionated preparations. It is several fold more sensitive than the conventional detection of harmol glucuronide by TLC, making it possible to distinguish the low and high affinity forms of UDPGT of adult human liver and to detect the low affinity form in fetal cells. The possible participation of both forms of GT in adults under different conditions and the apparent lack of the high affinity form in the fetal liver is discussed. PMID- 2111644 TI - What is the meaning of the expired CO2 waveform? PMID- 2111645 TI - Regional anesthesia for repair of Zenker's diverticulum. PMID- 2111646 TI - The dimensional stability of self-disinfecting alginate impressions compared to various immersion regimes. AB - Alginate impressions of a master acrylic study model pair were made in order to assess the effect of various disinfection techniques on dimensional stability. Impressions were made using self-disinfecting alginate, traditional alginate which had been dipped or soaked in a disinfecting solution, and included was a control group which was not disinfected. Inter- and intra-arch linear measurements of the resultant study casts were made using a Reflex Metrograph. The small differences found for the variables measured were not statistically significant. PMID- 2111647 TI - The timing of treatment for Class II malocclusions in children: a literature review. AB - Two basic strategies for the timing of treatment for Class II malocclusions in children are common: (1) correction achieved in two phases, one during pre adolescence (early treatment) and the other during the teen years; and (2) correction accomplished in one phase of active treatment during the adolescent years. The issues of efficacy and cost(risk)-benefit of these strategies have not been well delineated. Most clinical studies examining these issues have suffered serious methodological deficiencies, such as being retrospective, lacking adequate controls, and evaluating only successfully treated cases. However, despite a lack of objective data, clinicians have shown considerable interest in recent years in two-phase treatment. This paper reviews major issues of two-phase Class II treatment and concludes by delineating several important clinical questions which could be resolved by a carefully controlled prospective study. PMID- 2111648 TI - Quantitative analysis of litigation costs. PMID- 2111649 TI - Screening for thyroid disease. AB - PURPOSE: To evaluate the usefulness of screening for thyroid dysfunction in various clinical settings. DESIGN: Review and synthesis of the literature. MAIN RESULTS: Screening in the community detects new overt thyrotoxicosis or hypothyroidism in approximately 0.5% of the general population. The yield is best among women over 40 years of age (1%) and is lowest among young men (0%). Case finding (testing clinic patients who are seeing a physician for unrelated reasons) has a better yield and is less expensive than screening in the community. Patients hospitalized with acute illnesses do not benefit from routine thyroid function testing. However, patients who are admitted to specialized geriatric units because of general disability, failure to thrive, and other indications may benefit. In various studies, from 2% to 5% of patients admitted to geriatric units have treatable thyroid disease. The serum total thyroxine, free thyroxine index, free thyroxine, and sensitive thyrotropin assay are all effective as initial tests for screening. The sensitive thyrotropin assay is less cost-effective than the other choices. RECOMMENDATIONS: Case-finding in some women over 40 years of age can be useful. Patients admitted to specialized geriatric units may also benefit from routine testing. Thyroid function tests are not indicated for community screening programs or for patients hospitalized with acute medical or psychiatric illnesses. PMID- 2111650 TI - [Anti-Scl-70 antibodies in systemic scleroderma]. AB - We looked for anti-Scl-70 and anti-centromere antibodies in 109 patients (26 men and 83 women). Mean age was 43 +/- 15 years. Forty patients had systemic sclerosis according to ARA criteria. The extension of cutaneous involvement was defined by using Barnett and Coventry criteria: 12 patients were type I (sclerodactyly), 20 type II (acrosclerosis) and 8 type III (diffuse scleroderma). Among the 12 patients with type I, there were 8 cases of CREST syndrome defined as follows: presence of sclerodactyly, Raynaud's phenomenon and 2 of the 3 following criteria: oesophageal dysmotility, calcinosis, telangiectasia. Other organ involvement was recorded. Control patients had idiopathic Raynaud's phenomenon (n = 22), other connective tissue diseases (n = 20), and miscellaneous diseases (n = 28). Ninety-nine patients were prospectively included in this study. Patients' sera were stored at -20 degrees C. Ten previously stored sera obtained from patients with systemic sclerosis were also analyzed. Immunological tests were performed simultaneously and with no information on the diagnosis. When antinuclear antibodies were detected by indirect immunofluorescence, double immunodiffusion and immunoblotting were performed. Anti-Scl-70 antibodies were detected in systemic sclerosis only: 1 of 12 type I, 11 of 20 type II and 4 of 8 type III. One serum negative by immunodiffusion was positive using immunoblotting. We found that the specificity of anti-Scl-70 antibodies for systemic sclerosis was 100 p. 100 and their sensitivity 40 p. 100. There was a correlation between the presence of anti-Scl-70 antibodies and the presence of antinuclear antibodies (p less than 0.05) and the extent of cutaneous involvement (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111651 TI - [The in vitro activity of veterinary antiseptics]. AB - The in vitro activity of 28 veterinary antiseptic drugs was studied on 4 bacterial strains either with or without calf serum. Eight preparations (VT Dose, Dulcidrine, Collyre Clement, Cronic, Detecaine, Lotion Maudor, Tano-Patt, Aurikan), half of which were eye-lotions, were found to be non antiseptic according to AFNOR standards. In the presence of calf serum, 4 other preparations (Albacetine, Nybocaine, Pediplasme, Pedifort) did not meet the standard NF T 72.171 criteria. PMID- 2111652 TI - The serology of hepatitis C virus in relation to post-transfusion hepatitis. AB - Natural history studies conducted over the past 15 years have shown that parenterally transmitted non-A non-B hepatitis infection frequently results in an indolent chronic disease with serious long-term consequences. The recent identification of nucleic acid sequences comprising the genome of hepatitis C virus (HCV) has allowed the development of a serological assay based upon recombinant viral proteins specifically associated with the major agent of non-A, non-B hepatitis infection. The HCV antibody assays have now been applied to sera from blood donors worldwide, as well as various population samples with increased hepatitis risk in the course of clinical trials conducted in both Europe and the United States. Data from these studies provide further encouragement that assays based on the hepatitis C virus recombinant proteins are highly specific for the major agent of non-A non-B hepatitis and will provide a firm basis for blood donor screening and future diagnostic tests. PMID- 2111653 TI - Immunosuppressive mechanisms in pure red cell aplasia--a review. AB - Pure red cell aplasia (PRCA) has been associated with a variety of clinical disorders, and various autoimmune mechanisms have been described to account for the red cell suppression. Primary PRCA occurs via both humoral and cell mediated mechanisms. Recent evidence using gene rearrangement studies indicates PRCA with T-lymphocytosis is a clonal chronic T cell lymphoproliferative disorder in which the T cells suppress erythropoiesis. Called T cell lymphocytosis and cytopenia (TCLC), this disorder has unique features, such as frequent rheumatoid arthritis (RA) and neutropenia. A subset of this disorder with natural killer (NK) like cells also exists, though direct NK cell suppression has not been proven. In secondary PRCA, both humoral and cellular suppression of erythropoiesis have also been described, except in chronic lymphocytic leukemia (CLL) where T cell suppression primarily accounts for the red cell aplasia. A role for the cell adherent layer of the bone marrow, including macrophages, has also been demonstrated. PMID- 2111654 TI - Prostaglandin H synthase and xenobiotic oxidation. AB - We have attempted in this article to summarize and review cooxidation reactions that occur during the metabolism of AA and potential roles that these reactions can play in the activation and detoxification of chemicals. This review summarizes approximately 15 years of intensive investigation by a number of laboratories, and as such not all studies are cited, and in some cases data are not discussed with the emphasis that the original investigators may have intended. The major focus of many of these studies has been toward carcinogenesis. In the future, emphasis may shift to the formation of metabolites that will lead to other toxic effects. The cooxidation reactions that occur during AA metabolism are dependent upon the peroxidase activity of PHS. For some chemicals that are not cosubstrates, the epoxidation reactions that occur are dependent upon the subsequent formation of peroxyl radicals. A large and diverse number of chemicals are metabolized by an equally large and diverse number of chemical reactions. The unifying theme is the free radical nature of these oxidations. The subsequent reactions that these chemicals undergo is dictated by the nature of the free radical and the environment in which it is generated. Ample evidence now exists for the contribution of these free radical-mediated reactions not only in the formation of toxic metabolites, but also in some cases in the detoxification of chemicals. The overriding factor for this type of metabolism to occur is the relative concentrations in the specific tissue of PHS and peroxyl radicals with respect to other activating systems, particularly the monooxygenase system. In vivo investigations support the importance of the peroxidase and peroxyl radical systems in both activation and detoxification of chemicals in extrahepatic tissues. PMID- 2111655 TI - G proteins in signal transduction. PMID- 2111656 TI - Tissue plasminogen activator: the biochemistry and pharmacology of variants produced by mutagenesis. PMID- 2111657 TI - Penicillin-binding protein 3 of Listeria monocytogenes as the primary lethal target for beta-lactams. AB - Penicillin-binding proteins (PBPs) of Listeria monocytogenes were detected by their ability to bind to [2,3-3H]benzylpenicillin. Five proteins with Mrs of 95,000, 84,000, 80,000, 76,000, and 49,000 were detected. PBPs 1 to 4 had a high affinity for [2,3-3H]benzylpenicillin and were relatively scarce (80 to 150 molecules per cell). In contrast, PBP 5 was more abundant (600 molecules per cell) but had a low affinity for [2,3-3H]benzylpenicillin. L. monocytogenes has a relatively high natural resistance to cephalosporins. Competition experiments showed that cephalosporins bound very poorly to PBP 3 but were good inhibitors of PBPs 1, 2, and 4, which were completely blocked at concentrations well below the MIC. Analysis of a spontaneous imipenem-resistant mutant revealed that resistance was likely due to an altered PBP 3 with a reduced affinity for [2,3 3H]benzylpenicillin. These results suggest that PBP 3 is a primary lethal target for beta-lactams in L. monocytogenes. PMID- 2111658 TI - Determination of optimal dosage regimen for amikacin in healthy volunteers by study of pharmacokinetics and bactericidal activity. AB - The pharmacokinetics and serum killing curves of amikacin, which was administered by a 30-minute intravenous infusion of single doses of 7.5 mg/kg and then 15 mg/kg, were investigated in six healthy volunteers who received the two doses in a crossover study with a washout period of 20 days. The serum killing curves were determined for four bacterial species: Escherichia coli, Serratia marcescens, Enterobacter cloacae, and Pseudomonas aeruginosa. All strains were serum resistant, and the bactericidal activity was analyzed by separating the early phase (first 5 h) and the late phase (24 h) of the killing curve. For the early phase, the bactericidal activity was evaluated by correlating an index of surviving bacteria with amikacin concentrations. This methodology allowed determination of two parameters: the maximal effective concentration and the lowest effective concentration. For the late phase, the threshold values separating bacteriostatic and bactericidal activities were lower than 10 mg/liter for each strain. The concentration dependence of amikacin bactericidal activity was confirmed for Escherichia coli and Enterobacter cloacae and, to a lesser extent, for Serratia marcescens and Pseudomonas aeruginosa. Correlation of these data with amikacin pharmacokinetic data in volunteers indicated that a daily dose of 15 mg/kg may be effective in the treatment of Escherichia coli and Enterobacter cloacae infections. For Pseudomonas aeruginosa and Serratia marcescens, the partially time-dependent activity probably necessitates two daily administrations and combination with another antibiotic. PMID- 2111659 TI - Use of Saccharomyces cerevisiae expressing beta-galactosidase to screen for antimycotic agents directed against yeast cell wall biosynthesis and possible application to pathogenic fungi. AB - Saccharomyces cerevisiae expressing beta-galactosidase was used to develop a screen for compounds active against formation of the yeast cell wall. The screen detailed here is based on the release of beta-galactosidase from cells which had received an osmotic shock. PMID- 2111660 TI - Different doses of cefetamet pivoxil (Ro 15-8075) in the treatment of acute uncomplicated gonococcal urethritis in men. AB - In an open, dose-finding study, a 100% cure rate was observed in patients suffering from uncomplicated gonococcal urethritis who were treated with a single oral dose of either 1.2 g (n = 10), 0.8 g (n = 11), or 0.4 g (n = 10) of cefetamet pivoxil. The MICs of cefetamet for all gonococcal strains ranged from 0.001 to 0.12 micrograms/ml, and the MIC for 90% of the strains tested was 0.008 micrograms/ml. Cefetamet pivoxil was ineffective against Chlamydia trachomatis in 3 of 31 patients. Side effects were minor. PMID- 2111661 TI - US Supreme Court to hear first 'right-to-die' case. PMID- 2111662 TI - [Treatment of liver metastases from colorectal cancer--major hepatic resection and continuous hepatic arterial infusion chemotherapy]. AB - From April 1983 to April 1989, 123 cases of liver metastases from colorectal cancer were treated. Forty-three cases underwent hepatic resection. Forty had 5 FU, MMC, and ADM infusion chemotherapy through arterial catheter (FAM i.A.). The remaining had other treatment. In this study, 43 cases of hepatic resection and 32 out of 40 cases of FAM i.A. were evaluated. Thirty-nine of the 43 had major hepatic resection with regional lymph nodes dissection and 4 had partial hepatectomy. Regional lymph-nodes metastases were seen in 5 out of 39 dissected (12.8%). Small liver metastases which could not be diagnosed before or at surgery, were existed in 4 of 15 multiple liver metastases (26.7%). Three-year survival rates, calculates by Kaplan-Meier's method, were 53.5% in all, 57.4% in the solitary, and 42.8% in the multiple metastases. Three-year survival rates of the recurrences were 55% in the extra-hepatic and 24.5% in the hepatic recurrences. FAM i.A. was completed in 32 unresectable liver metastases. Responses of the FAM i.A. were observed in 21/32 (65.6%). Fifty percent survival rates were 11.7 months in all and 22.2 months in 13 cases without extra-hepatic lesions. Considering risk factors (multiple or large solitary metastases, unrecognized small liver metastases, lymph nodes metastases), major anatomic hepatectomy with lymph nodes dissection may be the treatment of choice for liver metastases from colorectal cancer. FAM i.A. had a good local response. PMID- 2111663 TI - [Combined treatment by hepatectomy and postoperative chemotherapy via a catheter in the hepatic artery of metastatic liver tumors]. PMID- 2111664 TI - [New treatments for urogenital toxicity of anti-neoplastic chemotherapy]. AB - Renal dysfunction and urinary disorders are the most troublesome adverse reaction to anticancer agents such as cisplatin (CDDP) and ifosfamide (IFM). A number of antidotes such as sodium thiosulfate (STS), WR-2721, thiourea, diethyldithiocarbamate and bismuth subnitrate have been tested to reduce the nephrotoxicity of CDDP. One notable method previously reported by Baba et al. and Pfeifle et al involves the i.v. administration of STS to prevent the nephrotoxicity of CDDP given locally. Since STS has been proven clinically effective in reducing such side effects, we initiated a study of STS in patients with advanced non-small-cell lung carcinoma who were given a combination of CDDP and vindesine (VDS) systemically. Urinary levels of beta 2-microglobulin (BMG) and N-acetyl-beta-D-glucosaminidase (NAG) were measured as an index of proximal tubular function. Analysis of both levels indicated that STS suppressed CDDP nephrotoxicity to a minimal level. Therefore, the present study clearly demonstrates that systemic administration of STS reduces the side effects of CDDP to a minimal level without impairing its antitumor activity and that STS treatment is applicable in a repeated chemotherapy using CDDP alone or in combination with other antitumor agents. Furthermore, it has been reported that urinastatin and fosfomycin may exert potent effects to reduce untoward nephrotoxicity of CDDP. IFM causes urinary disorders such as hematuria, reducing its clinical usefulness, Sodium 2-mercaptoethane sulfonate (mesna) is the thiol compound which binds specifically to the urinary toxic metabolites of IFM, and thereby decreases the undesirable effect of IFM on the lower urinary tract, especially on the bladder. Recently, it was reported by a Osaka mesna study group that mesna is useful for the prevention of IMF-induced urinary disorders. It was considered that above new treatments were required in repeating chemotherapy which induced urogenital toxicity. PMID- 2111665 TI - [Anisoylated plasminogen streptokinase complex during the acute phase of myocardial infarction. Results of a multicenter double-blind study versus heparin]. AB - Two hundred and thirty-one patients admitted to hospital within 5 hours of the onset of symptoms of a primary myocardial infarction were randomised into 2 groups: one received thrombolytic therapy [anisoylated plasminogen streptokinase activator complex (APSAC): 30 IU in 5 minutes] and the other was given conventional heparin therapy (5,000 IU). Heparin was given to both groups 4 hours later (500 IU/kg/day); the APSAC (N = 119) was identical with respect to age, location of infarct, Killip classification, delay before randomisation (188 +/- 62 minutes). Coronary angiography and ventriculography were performed after 3.4 +/- 1.2 days, and angioscintigraphy and myocardial scintigraphy after 19 +/- 2.5 days to determine the size of the infarct and the quality of left ventricular function. Coronary patency was much higher in the APSAC group (77%) than the heparin group (37%) (p less than 0.001). The angiographic ejection fraction was significantly greater in the thrombolytic group than in the heparin group (53 +/- 13% vs 47 +/- 12%, p less than 0.002), the difference being statistically significant in the anterior and inferior infarct subgroups. At the third week, the difference remained significant in the anterior infarct subgroup: a 31 per cent reduction in necrosed myocardial mass was observed in the APSAC group (33% in anterior infarcts: p less than 0.05 and 16% in inferior infarcts: NS). The limitation of infarct size explained the smaller reduction in left ventricular systolic function (r = 0.73; p less than 0.01). The hospital and one year mortality was comparable in the two groups which was not surprising given the small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111666 TI - [Long-term prognosis of coronary artery spasm]. AB - This study analyses the long-term prognosis of 210 patients with coronary spasm documented at coronary angiography. All patients with a previous history of myocardial infarction or who had undergone coronary angioplasty were excluded. The average follow-up was 55 months and only 11 patients were lost to follow-up. The actuarial survival figures showed the 1 year, 2 year and 5 year survival rates to be 95, 92 and 89 per cent respectively. Extracardiac mortality was mainly related to smoking (lung cancer, laryngeal cancer, etc.) and was higher than cardiac mortality. More than half of the cardiovascular events (sudden death, myocardial infarcts) occurred during the first year of follow-up. Ten patients (4.7%) died suddenly. The predictive factors of this event were: previous syncopal episodes or syncopal angina due to coronary spasm, percritical arrhythmias and the documentation of multiple spasms at coronary angiography. Myocardial infarction was observed in 10.6 per cent of patients. Only those with significant coronary arterial lesions developed this complication. At the end of the follow-up period, 75 per cent of patients were asymptomatic or had only atypical chest pain. No significant differences were observed between the two groups treated medically, by aortocoronary bypass or by the association of coronary bypass and plexectomy with the exception of non-lethal myocardial infarcts being significantly less common in patients treated medically. Therefore, the long-term prognosis of patients with coronary spams is relatively satisfactory. PMID- 2111667 TI - [Contribution of Doppler echocardiography to the evaluation and monitoring of normal and pathologic mitral valve prostheses]. AB - Doppler echocardiographic examinations were performed in 146 patients with normal and 42 patients with pathological (31 regurgitations and 11 obstructions) mitral valve prostheses confirmed by catheterisation and/or surgery. The maximum and mean transprosthetic gradients and pressure half times (PHT) were calculated from continuous wave Doppler recordings and regurgitant signals were searched for by continuous and pulsed wave Doppler. In the group of normal mitral valve prostheses, the mean gradients and PHT were very variable even within the subgroups of the same type and size of prosthesis. The best haemodynamic profile was observed with the St Jude prosthesis (mean gradient = 5 +/- 2 mmHg, PHT = 90 +/- 22 ms, p less than 0.05 vs other prostheses). Minimal mitral regurgitation was detected in 12 per cent of bioprostheses and 20 per cent of mechanical prostheses. No correlations were found between the mean pressure gradient or PHT and the size of the prostheses. Regular Doppler echocardiographic follow-up over 2.4 years was obtained in 25 patients and showed a remarkable stability of the Doppler parameters in 17 patients whereas prosthetic valve dysfunction was diagnosed in the other 8 cases. In the group of pathological mitral valve prostheses, regurgitation (N = 31) was associated with a high early diastolic pressure gradient (20.2 +/- 8 mmHg) and a normal or shortened PHT (84 +/- 28 ms). Obstructed prostheses (N = 11) had high mean pressure gradients (17 +/- 5 mmHg) and increased PHT (195 +/- 53 ms). All cases of obstruction were correctly identified by the Doppler but 4 prosthetic valve regurgitations were missed or underestimated (4 mechanical prostheses).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111668 TI - [Surgery of endomyocardial fibrosis. Apropos of 32 cases]. AB - From 1971 to 1984, 32 patients with endomyocardial fibrosis (EMF) were treated by endocardial resection (decortication) and valve replacement. The population consisted in 20 men and 12 women (age ranged from 8 to 64); 19 patients were european and 13 african. All were symptomatic, 78 p. 100 in stages III or IV of the NYHA. Hypereosinophilia was detected in 21 patients and its cause was determined in 11 cases. Cardiac involvement was biventricular in 22 patients and monoventricular in 10 patients. Six patients died in the immediate postoperative period and 6 late deaths were observed, owing to extracardiac causes in 4. There were no recurrence of EMF. Despite a high mortality rate, the authors suggest that all symptomatic EMF should benefit from endocardial resection. PMID- 2111669 TI - [Wolff-Parkinson-White syndrome. Value of intravenous flecainide for detecting Kent's pathways with short refractory period]. AB - The aim of this study was to assess the value of a non-invasive test in detecting accessory pathways with short anterograde effective refractory periods (AERP) (less than or equal to 270 ms) in patients with the Wolff-Parkinson-White syndrome. An intravenous injection of Flecainide acetate was administered to 19 consecutive patients referred for electrophysiological investigation of a WPW syndrome with permanent pre-excitation of the surface electrocardiogram. The first 8 patients (Group I) received a dose of 1.5 mg/kg over 5 minutes and the following 11 patients (Group II) were given 2 mg/kg in 5 minutes. In Group I, preexcitation disappeared in 3 patients (37.5%) who all had accessory pathways with AERP greater than 270 ms. It persisted in the other 5 patients (62.5%) of whom 4 had AERP less than or equal to 270 ms and 1 an AERP greater than 270 ms (false negative). In Group II, preexcitation disappeared in 8 patients (72.2%) of whom 4 had AERP greater than 270 ms and 4 had AERP less than 270 ms (false positives). Preexcitation persisted in the 3 other patients (27.3%); the AERP was less than or equal to 270 ms in 2 patients and greater than 270 ms in the other patients. These results suggest that intravenous Flecainide acetate at the dose of 1.5 mg/kg could be useful in differentiating WPW syndromes with long refractory periods (greater than 270 ms) from those with short refractory periods (less than or equal to 270 ms) with a satisfactory sensitivity and specificity, and that further studies on larger numbers of patients are required to confirm this hypothesis. PMID- 2111670 TI - [Changes in mitral and tricuspid blood flow as a function of aging. Value of a combined study with Doppler echocardiography]. AB - The many factors, especially physiological, which influence mitral diastolic flow and the difficulties in interpretation motivated this study of age related changes of blood flow through the two atrioventricular orifices, taking tricuspid flow as the reference for evaluation of any change in mitral flow. Doppler echocardiographic studies were performed in 45 normal subjects who were divided into 3 groups according to age. The amplitude, duration and velocity time integrals (VTI) of the E and A waves were studied at the level of the valve rings and at the tips of the leaflets. Ventricular isovolumic relaxation periods were measured. The following age-related changes were observed at both atrioventricular valve orifices: increased amplitude and VTI of the A waves; decreased amplitude and VTI of the E waves, leading to a decrease or inversion of the ratios of the E/A wave amplitudes and VTI. No significant differences in the duration of the E and A waves were detected. An increase in the left ventricular isovolumic relaxation period was observed. Differences were also recorded according to the site of the Doppler sample volume: increased amplitude, duration and VTI of the E and A waves when the flow was recorded at the tips of the valve leaflets. This underlines the value of using the E wave VTI/total VTI ratio which was unaffected by the sample volume position. An age-related decrease in this ratio was demonstrated at both atrioventricular valve orifices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111671 TI - [Results of the surgical treatment of tetralogy of Fallot before 6 months of age. A consecutive series of 62 cases with 49 complete repairs]. AB - From January 1980 to July 1988, 62 infants aged under 6 months with an uncomplicated Tetralogy of Fallot (single ventricular septal defect, normal coronary arteries, no localised pulmonary artery branch stenosis) underwent 64 surgical procedures. The indications for surgery were increasing cyanosis and/or anoxic spells. Fourteen systemic-pulmonary shunts (21.5%), 49 complete repairs (75.4%) and one enlargement of the right ventricular outflow tract and of the main pulmonary artery without closure of the ventricular septal defect, were performed. The results of palliative shunts are preoccupying: cumulative mortality of 36 per cent; high rate of early reoperation for complete repair: 14 per cent. Complete repair was associated with an operative mortality of 14 per cent. Only one child had to be reoperated. There was no late death after complete repair compared with 2 late deaths after shunt. Ultimate results of complete repairs are good. Some risk factors were statistically significantly associated with complete repair: age (2.5 months or less), weight (4,500 g or less), measurements of the pulmonary arteries estimated by the diameter of the right pulmonary artery (5 mm or less). Conversely there was no death in the subgroup of 31 infants aged more than 2.5 months without major pulmonary hypoplasia (diameter of the right pulmonary artery over 3.5 mm). One-stage complete repair give the best short and medium-term surgical results in treatment of uncomplicated Tetralogy of Fallot in infants, irrespective of age and weight providing they have no diminutive pulmonary arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111672 TI - [Is the prognosis of non-thrombolysed inferior infarction benign?]. AB - Between 1978 and 1983, 2,970 coronary angiographies were performed at the Cardiology Clinic of Necker Hospital; 220 survivors of an initial Q-wave inferior infarction who had not received thrombolytic therapy were selected. The ejection fraction was 55 +/- 11 per cent, and the indexed end diastolic left ventricular volume was 108 +/- 29 ml/m2. The left anterior descending artery was diseased in 57 per cent of cases. The incidence of multivessel disease was 67 per cent. Two hundred and eleven patients (96%) were followed up for 79 +/- 22 months. The prevalence of cardiovascular events was: cardiac deaths: 22 (10%), recurrent infarction: 20 (9%), angina requiring coronary bypass surgery: 60 (28%), cardiac failure: 22 (10%). The 10 year actuarial survival was significantly lower in patients with an ejection fraction less than 45 per cent (46% vs 91%) and in patients with triple vessel disease (62% vs 92% and 88%). The survival was not lower in patients with stenosis of the left anterior descending artery. PMID- 2111673 TI - [Signal-averaged electrocardiography in right ventricular dysplasia]. AB - The authors report their experience of signal-averaged electrocardiography (SAE) in arrhythmogenic right ventricular dysplasia (ARVD) in a study comparing the results in 40 control subjects, 21 patients with ARVD with episodes of sustained monomorphic ventricular tachycardia (VT) (Group I), 7 patients with ARVD without sustained VT (Group II) and 10 asymptomatic members of the families of patients in Group I (Group III). There were significant differences in the results of SAE in the time domain between the control group and Group I, patients with "classical" ARVD. The RMS 40 (root mean square of the last 40 ms of the QRS complex) was the most sensitive parameter but the specificity was less than the averaged QRS width and the low amplitude signal duration. The results in Group II were more varied, some patients having clearly abnormal SAE and others strictly normal recordings. In Group III, the investigation was normal. Spectral analysis after Fourier transformation did not show significant differences between the 3 groups. A difference was observed between the diffuse and localised forms of ARVD in Groups I and II: the localised forms had a shorter QRS width and low amplitude signal duration than the diffuse forms. Also, there was a relationship in Group I between age and duration of QRS and delayed potential which increased and with the RMS 40 or 50 which decreased. This is an argument in favour of the progressive nature of ARVD with respect to time. PMID- 2111674 TI - [Prognostic value of two-dimensional echocardiography before aneurysmectomy in anterior aneurysm of the left ventricle]. AB - The prognostic value of echocardiographic apical 4 chamber recordings was assessed retrospectively in 18 patients who underwent left ventricular aneurysmectomy following anterior wall myocardial infarction. After an average follow-up period of 2 years, 7 patients had died or remained in functional Classes III or IV (Group 1) and 11 patients had satisfactory clinical outcomes (Group 2). There were no significant clinical or coronary angiographic differences between the two groups. The left ventricular surface area, transverse diameter and fractional shortening of the surface were also comparable in the two groups. The surface area of the aneurysm was greater in patients in Group 1 (37.4 +/- 11.8 cm2 vs 21.1 +/- 15.8 cm2, p less than 0.05). However, the more discriminating parameters were those related to the non-aneurysmal contractile zones (NACZ). Patients in Group 1 had a smaller relative surface area of the NACZ than those in group 2; 6 of the 7 patients in Group 1 had NACZ of less than 40 per cent of the left ventricle compared with none of the patients in Group 2 (p less than 0.001). In addition, the function of the NACZ was significantly worse in Group 1: surface fractional shortening: 9.6 +/- 10.2% vs 32.6 +/- 8.3% (p less than 0.001); ejection fraction: 20.7 +/- 9.1% vs 41.6 +/- 6.1% (p less than 0.001). All patients in Group 1 and none in Group 2 had ejection fractions of the NACZ of less than 30 per cent. Therefore, the apical 4 chamber view provides valuable prognostic information in patients who are candidates for surgical resection of left ventricular anterior wall aneurysms. PMID- 2111675 TI - [Progression from hypertrophic obstructive cardiomyopathy to dilated cardiomyopathy. Apropos of 4 cases]. AB - Four cases of hypertrophic obstructive cardiomyopathy diagnosed on clinical, phonomechanographic, echocardiographic and haemodynamic criteria progressing to dilated cardiomyopathy are reported. This evolution was observed over a number of years (up to 20 years) and was accompanied by a clinical aggravation in all cases with 2 deaths and atrial fibrillation in 3 of the 4 cases. The signs of intraventricular obstruction [systolic murmur, bulge on the carotid pulse tracing, systolic anterior motion of the mitral valve (SAM) and intraventricular pressure gradient] disappeared as the left heart chambers dilated with a reduction in ventricular wall motion and parietal thinning but no change in myocardial mass. PMID- 2111676 TI - [Tolerance of treatment with nitrate derivatives]. AB - Tolerance to treatment with nitrate derivatives, suspected for many years and often ignored in everyday clinical practice, has recently been the subject of much study. Although the phenomenon has been clearly demonstrated in patients on long-term therapy, it seems to vary from patient to patient, with the underlying pathology and the galenic form of nitrate used. The mechanism of tolerance to nitrates is multifactorial, related on the one hand to depletion of sulfhydryl groups in the body and on the other to activation of the sympathetic and renin angiotensin systems. The administration of sulfhydryl groups in the form of N acetylcysteine partially restores the effects of nitrates in some patients. PMID- 2111677 TI - [Mechanisms of exertion dyspnea in cardiac insufficiency]. AB - Effort dyspnea in cardiac failure corresponds to a subjective perception of difficulty in breathing which is itself secondary to a disproportion between the central bulbar respiratory regulation and the level of pulmonary ventilation attained. In cardiac failure, this situation is the result of dysfunction of both the respiratory apparatus and the skeletal striated muscle during exercise. During exercise a rise in left ventricular end diastolic pressure causes: a reduction in pulmonary compliance. The bronchial and alveolar capillaries drain into the pulmonary veins. The congestion of these capillaries and the resulting oedema makes the lung "stiffer"; an increase in the resistances of the small airways due to direct compression by congested bronchial vessels. The physiological dead space increases: the respiratory muscles ventilate pulmonary zones which are not perfused to no benefit. The reduction of pulmonary compliance, the increased resistances of the airways and of the physiological dead space all contribute to increase the work of the respiratory muscles. In addition to these mechanical phenomena, there is greater stimulation of the respiratory centre in the brain stem by the metabolic abnormalities of the skeletal striated muscles. During effort, they rapidly function under anaerobic conditions and the resulting hyperproduction of lactate and carbon dioxide stimulates the respiratory centres. PMID- 2111678 TI - [Cellular mechanisms of pulmonary vasoconstriction in an experimental model of protamine reversal of heparin]. AB - The neutralisation of heparin by protamine can cause life-threatening pulmonary hypertension. We studied this reaction in animal experimental models (sheep and rat) to determine the cellular mechanisms of the pulmonary vasoconstriction. The heparin-protamine reaction (H-P) with pulmonary hypertension (peak of mean pulmonary artery pressure = 57.3 +/- 2.2 mmHg), decreased cardiac output (-20%), leukopenia (-30%) and plasma release of high concentrations of thromboxane B2 (6.03 +/- 0.03 ng/ml) was constantly observed in sheep. The reaction was identical in sheep with induced thrombocytopenia by administration of antiplatelet antibodies. On the other hand, the neutralisation of heparin by protamine in rats did not cause thromboxane release or pulmonary vasoconstriction although the leukopenia was identical to that observed in sheep. Therefore, the platelets and white blood cells did not seem to cause the pulmonary vasoconstriction induced by the H-P complexes. The inter-species difference observed suggests that pulmonary intravascular macrophages may be responsible for the liberation of eicosanoids and acute pulmonary vasoconstriction occurring during the neutralisation of heparin by protamine. PMID- 2111679 TI - [Cardiac sarcoidosis responsible for localized left ventricular ectasia and refractory ventricular tachycardia. Anatomoclinical study]. AB - The authors report the case of a 63 year old woman admitted to hospital for recurrent refractory ventricular tachycardia. Echocardiography and cardiac scintigraphy showed global left ventricular function. Ventriculography confirmed the left ventricular dysfunction and also showed a localised aneurysm of the anterior left ventricular wall. Surgical resection of the aneurysm and an encircling endocardial ventriculotomy were performed but the patient died of a low output syndrome. Pathological examination of the excised tissue showed granulomatous lesions associated with fibrosis interrupting the striated myocardial bundles. The granulomata consisted in a large number of epithelioid histiocytes and very large giant cells with many nuclei. The diagnosis made retrospectively was that of cardiac sarcoidosis causing a ventricular aneurysm and global left ventricular dysfunction. The diagnosis of cardiac sarcoidosis is difficult in the absence of systemic extracardiac involvement because the clinical manifestations and complementary investigations are non specific. The diagnosis may be made by endomyocardial biopsy in 25 per cent of cases, thereby leading to specific treatment with steroids which is sometimes effective. PMID- 2111680 TI - [Transient reduction of ventricular tachycardia with adenosine-5'-triphosphate. A possible action of ATP on purinergic receptors]. AB - The authors report the case of a 46 year old man in whom a regular, wide complex tachycardia was terminated temporarily by the injection of adenosine-5' triphosphate (ATP:Striadyne); endocavitary electrophysiological studies showed the tachycardia to be of ventricular origin. After aminophylline, an inhibitor of certain purinergic receptors, the tachycardia could be reproduced at will and was sustained whereas only short runs of tachycardia could be induced under basal conditions. The mode of action of the ATP on this type of tachycardia could be a direct effect of the molecule on the purinergic receptors specifically inhibited by aminophylline. PMID- 2111681 TI - [Ventricular tachycardia during theophylline overdose. Apropos of a case of reduction by magnesium chloride]. AB - The authors report a case of ventricular tachycardia (VT) induced by theophylline toxicity in a patient with ischaemic heart disease complicated by left ventricular failure and chronic asthma. Two episodes of VT were reduced by intravenous injection of magnesium chloride. The aggravating role of a moderate magnesium deficiency is suggested by the synergy of hypomagnesemia and theophylline on intracellular calcium fluxes contributing to an accumulation of intracytoplasmic calcium, a situation which has been shown experimentally to generate delayed after depolarisations. The respective roles of the correction of the metabolic deficiency and of the specific antiarrhythmic action related to the calcium blocking effect of magnesium salts at cellular level are discussed. PMID- 2111682 TI - [Relaxing factors of endothelial origin and coronary spasm]. AB - The endothelium releases a powerful vasodilating and anti-aggregant substance, the EDRF, both under basal conditions and after stimulation by a large number of hormones and endogenic factors. Endothelial lesions or dysfunction may play important roles in causing coronary spasm although other changes related to atherosclerosis must also be taken into consideration. One possible stimulus is aggregating platelets as they are an important source of vasoconstricting substances. The endothelium also secretes other vasoactive substances, EDHF and/or EDCF, the physiopathological role of which has not yet been established. PMID- 2111683 TI - [Application of ultrasono-micrometric technic to study vasomotility]. AB - An experimental model of simultaneous recording of pressure and flow (instantaneous and mean values) and of the vascular diameter (by ultrasonomicrometry) at the entry of a clearly limited territory of the systemic circulation has been developed in the animal together with a programme of data aquisition and analysis. This programme allows quantification of the different viscoelastic properties of the vessel wall which characterise arterial flow in the arteries of distribution (capacitance vessels) and irrigation (resistance vessels). The model was applied to the study of the pharmacological effects of two antianginal agents, a nitrate derivative (ND) administered acutely by slow intravenous infusion at a dose of 25 micrograms/Kg/mn over 20 minutes (total dose: 500 micrograms/Kg) and a substitute sydronimous substance (SYD) administered in the same manner at a dose of 15 g/Kg/mn over 20 minutes (total dose: 300 micrograms/Kg). The hypotensive effects obtained were comparable and significant (p less than 0.001) in both cases. The ND led to a fall in mean blood pressure of 9.7 +/- 1.3% and SYD of 10.0 +/- 2.1%. However, SYD led to an increase in aortic blood flow (11.7 +/- 3.6%, p less than 0.01) whilst the ND had no significant effect on this parameter (+ 6.07 +/- 5.7%). As a result, there was a much greater decrease of peripheral resistances after administration of SYD ( 22.8 +/- 3.1%) than with the ND (-12.7 +/- 4.2%). This difference was also observed when the input impedence of the vascular bed was studied (-31.2 +/- 6.9% after SYD and -12.0 +/- 2.5% after the ND).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111684 TI - [Blood flow and compliance of great arterial trunks]. AB - The important technical advances in the last few years in the field of ultrasonic imaging and Doppler velocimetry now enable an accurate evaluation of the vasomotricity, blood flow and compliance of the large peripheral arteries. The information provided by these new non-invasive techniques in clinical pharmacology is considerable as they make possible repeated measurements of different parameters of regional circulation (diameters, flow, pulse wave velocity and modulus of elasticity) and the assessment of the efforts of different vasoactive drugs on these values. Some limitations are nevertheless inherent to the non-invasive nature of the examination. PMID- 2111685 TI - [Value and study methods of hemorheology in vascular pathology and pharmacology]. AB - The growth of modern, reliable, reproducible and relatively inexpensive techniques of studying micro and macrorheological changes has confirmed the role of haemorheology in the physiology of the microcirculation and the consequences of its disturbance in vascular and ischemic pathology. These abnormalities can be corrected by pharmacological agents including several vasoactive molecules which owe at least some of their therapeutic effects to their action on blood rheology especially on the red blood cells. Systematic study of the rheological effects of these vasoactive, anti-ischemic substances is now possible and necessary. PMID- 2111686 TI - [The humeral artery and clinical pharmacology]. AB - Regional haemodynamic parameters such as blood flow, brachial artery diameter and forearm resistances may be measured or calculated non-invasively by pulsed Doppler techniques, and, in the absence of blood pressure changes, provide a method of observing and quantifying the vasomotor tone of small or large arteries. This type of study therefore allows characterisation of the vascular effects of drugs whether they be vasodilators or substances with a preferential mode of action on the myocardium. These effects can be situated with respect to the central hemodynamics in order to determine the presence of phenomena of regional redistribution of cardiac output, the regional vascular changes observed after taking a meal or in cardiac failure, with and without treatment; this should lead to a better understanding of the mode of action of drugs used in cardiovascular disease and also of the underlying physiopathological mechanisms. PMID- 2111687 TI - [Value of transcutaneous staged dynamic oximetry of stage II arteritis of the leg]. AB - The clinical and prognostic value of transcutaneous oxygen pressure measurements at rest has been established in Leriche Stage III and IV occlusive peripheral arterial disease but is controversial in Stage II because there is an overlap of transcutaneous pO2 (Tc pO2) values with those of normal subjects. The authors report the results of Tc pO2 measurements during exercise testing in a group of patients with Stage II occlusive arterial disease of the lower limbs. Seventy eight patients with an average age of 53 years (range 40 to 65 years) whose claudication perimeter and site of pain had been carefully assessed and who had also recently undergone Doppler arterial examination and arteriography and 35 control subjects with an average age of 54 years (range 45 to 70 years) were studied. The Tc pO2 was continuously measured with a multimodular Kontron Supermon at 4 different sites simultaneously: precordium (reference probe), thigh, calf and foot in the dorsal recumbent position after 30 minutes rest, during a standardised exercise stress test at 50 watts and during the recovery phase. The results were expressed as ratio of tissue oxygenation (RTO): thigh, calf or foot Tc pO2/precordial Tc pO2 X 100 in order to take into account the patients cardiorespiratory status and adaptation to exercise. The RTO in normal subjects remained at the upper limits of the resting value throughout exercise and then returned slowly to basal values during the recovery phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111688 TI - [Vasomotility of the bronchial circulation in cardiac failure]. AB - The bronchial circulation is a physiological left-to-left shunt; the venous return of the bronchial arteries vascularising the intra-pulmonary bronchi drains directly into the left heart chambers. In cardiac failure, increased left ventricular filling pressures affects the bronchial circulation and causes stasis and congestion. Congestion of the arterial and venous bronchial microcirculation leads to thickening of the bronchial mucosa and submucosa, resulting in a tendency to obstruct small and medium-sized airways. The bronchial circulation can be explored indirectly in cardiac failure by the spirometric response to adrenergic agonists and antagonists administered by inhalation: bronchial vasomotor phenomena explain the symptomatology of cardiac asthma and also seem to play a role in the genesis of the dyspnoea of effort in patients with cardiac failure. PMID- 2111689 TI - [Methods for evaluating vasodilator agents in cardiac failure]. AB - Invasive cardiac catheterisation remains the reference technique for the evaluation of the effects of vasodilator drugs in cardiac failure. The arterial, venous or mixed site of action can be determined. Venous vasodilators induce a fall in left ventricular end diastolic volume (EVD), left ventricular end diastolic pressure (EDP), and stroke volume (SV). Arterial vasodilators decrease left ventricular end systolic pressure (ESP), end systolic volume (ESV) and increase the stroke volume. Mixed vasodilators associate the effects of both, leading to a fall in left ventricular filling pressures and an increase in SV. It is not always easy to determine the exact site of action of a given vasodilator drug. Arterial vasodilatation can only be confirmed when peripheral arterial resistances and systemic blood pressure decrease simultaneously. Venous vasodilatation can only be formally confirmed by using other techniques such as pethysmography. Hemodynamic investigations have other fundamental objectives in the evaluation of the effects of a vasodilator, especially the demonstration of possible associated positive inotropic effects. This would be relatively easy in the case of a venous vasodilator which induces an increase in SV but more difficult in the assessment of an arterial vasodilator. Studying the distribution of regional blood flow after the administration of a vasodilator is another important objective of cardiac catheterisation. Although coronary flow can be studied properly, the hemodynamics of other regions can only be assessed approximatively. The phenomenon of tolerance at an early or late stage of vasodilator therapy can also be demonstrated by hemodynamic monitoring. PMID- 2111690 TI - [Methods for studying vasodilator agents in Raynaud's phenomenon]. AB - Raynaud's phenomenon is usually a benign acrosyndrome which few of the currently available therapies improve significantly. This makes the evaluation of the efficacy of vasodilators very difficult, especially as there are no standardised complementary investigations to quantify their effects. Assessment is based essentially on careful interrogation and the use of an analogical scale remains the method of reference. The multiplicity of factors inducing the acrosyndrome necessitates cross-over trials versus placebo over sufficiently long periods of observation (if possible, one month). As regards follow-up and objective evaluation, reactivity to cold is a promising method providing the tests can be standardised with respect to methodology and expression of results. PMID- 2111691 TI - [Methods for studying vasoactive drugs in arteriopathy of the leg and chronic venous insufficiency]. AB - Vasoactive drugs are widely prescribed in France. Over the last few years, some of these molecules have been evaluated by controlled clinical trials based on subjective assessment of their effects on the arterial or venous disease. Paraclinical investigations performed with a view to provide clinical pharmacological or physiopathological information give an indication as to the mode of action of these drugs but cannot, under any circumstances, be substituted for controlled clinical trials implying the inclusion of large patient population groups. PMID- 2111692 TI - [Comparative studies of superovulation in high-producing cows]. AB - PMSG-PG (1), PMSG-PG-anti-PMSG (2), and FSH-PG (3) were used under production conditions for superovulation treatment of high-yielding cows. An analysis of results has shown the FSH variant (3) to be superior with significance to the other two regimes. It yielded positive ovarian reactions (greater than or equal to 3 corpora lutea) in 92.0 percent of all cases, with 7.0 +/- 6.3 transferable embryos being obtained. Regime 1 gave only 75.5 percent as well as 3.2 +/- 2.97, while 85.5 percent and 4.3 +/- 3.9 were recorded from regime 2. Significance amounted to P less than 0.01; 0.001. Regimes 2 and 3 in standardised form are recommended for embryo transfer with cattle in breeding practice. PMID- 2111693 TI - [Accelerated desensitization with Dermatophagoides pteronyssinus in severe asthmatic children. Evaluation after one year of immunotherapy]. AB - An homogeneous group of 17 children with severe chronic asthma were given a rush immunotherapy with standardized Dermatophagoides pteronyssinus extracts. Maintenance dose was injected monthly for one year. Symptom and medication scores as well as functional (lung function tests, specific nasal challenges), immunologic and allergic parameters (skin tests, total serum IgE, specific IgE and IgG4) were recorded before and at the end of the study. Rush immunotherapy was well tolerated in spite of some moderate systemic adverse reactions. Symptom and medication scores improved in 10 children. Nasal and skin sensitivity decreased in respectively 3 and 7 children. However there was no correlation between the improvement of quality of life and laboratory results. This study shows that specific immunotherapy is possible in children with severe asthma. Its efficacy should be assessed by symptom and medication scores. PMID- 2111694 TI - Effects of zinc oxide-eugenol on leucocyte number and lipoxygenase products in artificially inflamed rat dental pulp. AB - The number of leucocytes and level of endogenous LTC4 in the pulp tissue were measured by a histological method and radioimmunoassay, respectively. When the mandibular incisor pulp was irritated by drilling a hole in the dentine without using any coolant, the number of polymorphonuclear leucocytes and lymphocytes and the concentration of LTC4 increased to 3.2, 1.9 and 1.8 times their respective levels in normal pulp 6 h after the injury. The total leucocyte number in blood collected from these rats was also increased significantly. In contrast, when the cavities cut in dentine were filled with a zinc oxide-eugenol mixture (powder: liquid 100 mg/25 microliters), the increase in the number of cells was significantly curtailed, and the LTC4 level fell to 50% of that in normal pulp within 1 h after the filling. No decrease in the LTC4 level was observed after filling with a zinc oxide-water mixture, but the level decreased in response to an increase in eugenol content in the zinc oxide-eugenol placed in the cavity. Biosynthesis of [14C]-HETE and HPETE from [14C]-arachidonic acid was inhibited by the addition of 10 microM eugenol to the pulp homogenate. Thus eugenol released from zinc oxide-eugenol inhibited the biosynthesis of lipoxygenase products and the early chemotactic accumulation of leucocytes. PMID- 2111695 TI - Tumor necrosis factor induced release of endothelial cell lipoprotein lipase. AB - The major functional pool of lipoprotein lipase (LPL) that hydrolyzes triglycerides in circulating lipoproteins is located on the vascular endothelium. The macrophage-secreted cytokine tumor necrosis factor (TNF), a molecule known to affect endothelial cell functions, was used to test the hypothesis that alterations of endothelial cell metabolism regulate the binding of LPL to these cells. TNF addition induced rapid (maximum release at 45 minutes) dissociation of LPL protein and activity from its binding sites on cultured porcine aortic endothelial cells. LPL release by TNF required endothelial cell metabolic event(s) which involved cell secretion. In addition, LPL release was inhibited by pertussis toxin, suggesting the involvement of guanine nucleotide regulatory protein(s). Addition of arachidonic acid, a molecule known to be released by endothelial cells due to phospholipase A2 activation by TNF treatment, released LPL from the cell surface. Furthermore, direct modulation of cellular phospholipase A2 activity also led to changes in the release of LPL. Our studies demonstrate that alterations in the cellular metabolism of endothelial cells, for example, by TNF, may release functional pools of LPL from the vascular endothelium. This decrease in LPL on endothelial cell surfaces might be involved in the development of hypertriglyceridemia and redirection of energy flow during infections and inflammation. PMID- 2111696 TI - Plasma catecholamine metabolites and polycystic ovary syndrome. AB - It has been postulated that catecholamine metabolism may be altered in cases of polycystic ovary syndrome. To search for possible correlations between catecholamine metabolism and hormonal disturbances, we have studied the serum LH, LH:FSH ratio, testosterone, and plasma catecholamine metabolites in patients with polycystic ovary syndrome and in control subjects with normal ovulatory cycles. The metabolites studied were 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4 dihydroxyphenylacetic acid (DOPAC) as markers of adrenergic activity and dopaminergic activity, respectively. The polycystic ovary was divided into 2 patterns [general cystic pattern (GCP) and peripheral cystic pattern (PCP)] as determined by ultrasound. The results were as follows: 1) Serum LH, LH:FSH ratios, and plasma MHPG levels in patients with polycystic ovary syndrome were significantly higher than in the controls. 2) In cases of polycystic ovary syndrome, serum LH, LH:FSH ratios, and testosterone showed no significant correlations with catecholamine metabolites. 3) Using the ultrasonographical classification, we found that plasma MHPG levels of the GCP group were significantly higher compared with the PCP group in patients with polycystic ovary syndrome. Thus, catecholamine metabolism is altered in patients with polycystic ovary syndrome, and ultrasonography revealed different patterns of catecholamine metabolism. PMID- 2111697 TI - Late (one month) reversible ischaemia after primary coronary occlusion treated with recombinant tissue plasminogen activator (rTPA). AB - The incidence of reversible ischaemia was assessed four weeks after primary coronary occlusion in 36 patients who had not required earlier revascularisation after randomisation to receive rTPA (n = 19) or placebo (n = 17). Coronary arteriography was performed at three weeks and thallium scintigraphy with dynamic stress testing at four weeks. Patients were followed for one year without planned intervention in the absence of symptoms. Managing physicians remained blinded to thrombolytic therapy. Patency rate of the infarct related artery at three weeks was greater after rTPA (rTPA 16, placebo 9; p = 0.04). Reversible perfusion defects within infarct related artery territory occurred with similar frequency in both treatment groups (rTPA 7, placebo 8). Multivessel disease was frequent (rTPA 11, placebo 12) but associated with a low incidence of reversible perfusion defects outside infarct related artery territory (rTPA 3, placebo 2). Thallium scintigraphy identified six of seven patients requiring subsequent revascularisation (sensitivity 86%, specificity 59%, negative predictive value 94%). Dynamic stress testing was positive for reversible ischaemia in 28% (rTPA 6, placebo 4) and identified two patients requiring revascularisation (sensitivity 29%, specificity 72%, negative predictive value 81%). The greater patency rate achieved with rTPA at three weeks after primary coronary occlusion was not associated with a significantly greater incidence of reversible perfusion defects at four weeks in patients who had not required prior revascularisation. The absence of reversible perfusion defects at four weeks was associated with a low incidence of revascularisation procedures during one year follow-up. PMID- 2111698 TI - Physiological and biochemical consequences of electroimobilisation in conscious sheep. AB - An electroimmobilisation device has been developed to facilitate the automated shearing of sheep, but there is little information on its effects on the body. We have studied its effects on the cardiovascular system and on intermediary metabolism in sheep. Electroimmobilisation caused statistically significant increases in mean arterial pressure, heart rate, cardiac output, renal and hepatic and hindquarter glucose and lactate flux, organ and whole body oxygen flux, hindquarter blood flow and core temperature and decreases in arterial and posterior vena cava blood pH, renal and hepatic blood flow and PaCO2. Notably, no change occurred in PaO2. The metabolic changes demonstrated the capacity of sheep to respond to the increased muscular and cardiovascular work induced by electroimmobilisation. Pulmonary function was not compromised during electroimmobilisation as judged from blood gas changes, and the acid/base changes were rapidly reversed after electroimmobilisation. The recovery to control conditions for all perturbations generally took no longer than 30 min, consistent with a rapid and physiologically adequate reversal by the animal's homeostatic mechanisms. PMID- 2111699 TI - Nucleotide sequences and three-dimensional modelling of the VH and VL domains of two human monoclonal antibodies specific for the D antigen of the human Rh-blood group system. AB - The nucleotide sequences were determined for the VH and VL domains of two human IgG1 antibodies, Pag-1 and Fog-B, specific for the D antigen of the Rh-blood group system. The VH-region genes of the two antibodies were derived from separate germ-line genes within the VH-IV gene family, but both antibodies used the same JH6 gene. The D-region genes differed from each other, and no similarity was found to known D regions. The light chain of Fog-B belongs to the V lambda-I subgroup and that of Pag-1 probably belongs to the V lambda-V subgroup; both light chains used the J2/3 gene. Three-dimensional models of the variable domains were made, based on those of known crystallographic structure. The surface contours at the combining sites are clearly different, consistent with the evidence that the antibodies recognize different but overlapping epitopes. Some details of the molecular modelling of hypervariable regions have been deposited as Supplementary Publication SUP 50155 (6 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1990) 265, 5. PMID- 2111700 TI - The oxidation of leucine in tumour-bearing rats. AB - Rats bearing the Walker-256 carcinosarcoma showed significant changes in leucine metabolism compared with their non-tumour-bearing controls. After a single intravenous tracer dose of L-[1-14C]leucine in vivo, 14CO2 release by tumour bearing rats was significantly elevated throughout the time course of administration. In addition, both the clearance and turnover rates of the tracer were significantly enhanced in these animals. Incubation of soleus muscles from control and tumour-bearing rats in the presence of L-[1-14C]leucine revealed an enhanced oxidation of the amino acid in the tumour-bearing group. Tumour tissue slices were also able to oxidize the tracer at a similar rate to that found in soleus muscles from control animals. PMID- 2111701 TI - Flow cytometry resonance energy transfer suggests an association between low affinity interleukin 2 binding sites and HLA class I molecules. AB - Using flow cytometry energy transfer we have studied the sterical proximity of interleukin 2 receptors and the heavy chain of the major histocompatibility complex at the surface of normal lymphocytes. Our data suggest that class I molecules may be part of a low-affinity interleukin 2 receptor multimolecular complex, where the MHC class I heavy chain is in close proximity to the actual interleukin 2 binding site, in contrast to the light chain (beta 2 microglobulin). PMID- 2111702 TI - Specific expression of lactase in the jejunum and colon during postnatal development and hormone treatments in the rat. AB - The expression of lactase was compared in the jejunum and colon of the rat at the levels of enzyme activity and protein and RNA content. We found that the enzyme proteins and the corresponding mRNAs share common features and are encoded by a single gene in both intestinal segments. In the jejunum, large amounts of lactase mRNA and proteins were detected during postnatal development as well as in adult rats, despite the 10-fold decline in lactase specific activity which occurs at weaning. In contrast, in the colon the expression of lactase was restricted to early postnatal development. In the colon, the enzymic activity of lactase and the amounts of protein and mRNA followed parallel development profiles with a peak at day 4 after birth. Injections of thryoxine or epidermal growth factor into neonates led to small modifications in the expression of lactase in the jejunum. On the other hand, these treatments caused a large decline in lactase activity in the colon that paralleled a decrease in the amount of lactase protein and mRNA. These data indicate that the expression of lactase is mainly regulated at the post-transcriptional level in the jejunum, whereas it is controlled at the pretranslational level in the colon. PMID- 2111703 TI - Nerve growth factor-induced increase in [3H]thymidine incorporation into parotid and submandibular glands of young rats and its partial blockade by propranolol or partial sialoadenectomy. AB - Administration of nerve growth factor (NGF) twice daily for 2 days to young rats (11 days old at the time of the initial injection) resulted in an 8.1-fold increase in [3H]thymidine levels of the parotid gland, and a 9.7-fold increase in levels of the submandibular gland when compared to untreated controls. Isoproterenol (ISO), a beta-adrenergic receptor agonist, caused an 8.7-fold increase in [3H]thymidine incorporation into DNA of the parotid gland, and a 10.7 fold increase in [3H]thymidine in the submandibular gland when compared to controls. The increase in thymidine was accompanied by parotid gland enlargement as well as an increase in cell surface beta 1-4 galactosyltransferase, an enzyme whose expression has been associated previously with acinar cell proliferation. Administration of NGF and ISO together were not additive in their effects on the parotid and submandibular glands. The introduction of propranolol, a beta adrenergic receptor antagonist, completely negated the ISO effects on the salivary glands but was only partially effective in blocking the NGF effects on the glands. An assay of parotid levels of norepinephrine showed NGF treatment to cause an increase in gland-associated levels of neurotransmitter. Removal of the submandibular/sublingual glands prior to administration of ISO prevented the above changes in the parotid gland. NGF administered to partially sialoadenectomized rats was also less effective in inducing parotid gland hypertrophy and hyperplasia. Simultaneous administration of NGF and ISO to the partially sialoadenectomized rats had an additive influence on [3H]thymidine incorporation, galactosyltransferase expression and gland hypertrophy. The results suggest that NGF influences salivary gland cell growth in part through activation of cell-surface beta-adrenergic receptors. PMID- 2111704 TI - Octopamine receptors in locust nervous tissue. AB - The octopamine binding site in the nervous tissue of the migratory locust Locusta migratoria is identified as an octopamine receptor of class 2. The binding of octopamine to the binding site is saturable, reversible, stereospecific and shows a pharmacological profile typical for octopamine receptors. Saturation analysis results in a single class of non-interacting binding sites (KD = 7.9 +/- 0.9 nM; Bmax = 160 fmol/mg). The pharmacological analysis shows that the phenyliminoimidazolidines NC7 and NC5 (Ki = 0.29 and 0.87 nM, respectively) are the most potent agonists, and that mianserin (Ki = 1.20 nM) is the most potent antagonist ever reported for octopamine receptors in direct binding studies. PMID- 2111705 TI - Sites of metformin-stimulated glucose metabolism. PMID- 2111706 TI - Comparison of the pretranslational regulation of FSH synthesis by gonadal steroids in rats and mice. AB - There are significant differences between rats and mice in the gonadal regulation of several aspects of gonadotroph function. To investigate whether these extend to the pretranslational regulation of FSH synthesis by gonadal steroids, we have measured FSH-beta mRNA levels following gonadectomy and sex-steroid replacement and have related these to serum and pituitary FSH as a reflection of overall hormone synthesis. In ovariectomized rats, FSH-beta mRNA levels increased by 8 h, decreased, and then rose progressively over the next 28 days. A similar pattern of response was observed in orchidectomized rats. In mice, there were progressive increases in FSH-beta mRNA levels in both males and females following gonadectomy, without evidence of the early peaks observed in rats. In both species, the change in FSH-beta mRNA levels after gonadectomy was greater in females than in males. These changes in FSH-beta mRNA following gonadectomy were paralleled by changes in the serum FSH concentration. In ovariectomized female rats and mice, pituitary FSH stores increased by 8 h and 3 days respectively, whereas in male rats, pituitary FSH content did not rise until 10 days after orchidectomy. The most striking species difference was the marked and prolonged reduction of pituitary FSH after orchidectomy of mice. Treatment of rats and mice from the time of ovariectomy, with a dose of oestradiol that prevents increases in serum LH, only partially attenuated the rises in FSH-beta mRNA and serum FSH and did not prevent the increase in pituitary FSH content. Treatment of intact or orchidectomized rats with testosterone suppressed FSH-beta mRNA levels to 50% below intact control values without affecting pituitary FSH content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111707 TI - Isolation, characterization, and mapping of a human acid beta-galactosidase cDNA. AB - A lambda gt11 human testicular cDNA library was screened with degenerate oligonucleotide probe mixtures based on amino acid sequence data generated from cyanogen bromide fragments and tryptic fragments of purified human beta galactosidase. Six positive clones were identified after screening 2 x 10(6) plaques. The sequences of these six clones were determined and found to be derived from two different cDNAs. The sequence of the longest of these cDNAs is nearly identical to that recently determined by Oshima et al. (1988). It codes for a 76-kD protein and all 11 peptides that were generated from the purified enzyme. The second clone is shorter by 393 bp in the central portion of the coding region. Analysis by Northern blotting revealed the presence of a single mRNA species of 2.45 kb in lymphoblasts and testicular tissue. It is deduced from the amino acid sequence data that proteolytic processing of the precursor form of beta-galactosidase must occur by cleavage in the carboxy-terminal portion of the polypeptide perhaps around amino acid 530 at a uniquely hydrophilic sequence. Using a probe generated from the 3' region of the cDNA, we have mapped the locus coding for human beta-galactosidase to chromosome 3p21-3pter. PMID- 2111708 TI - Sequence of the cDNA and 5'-flanking region for human acid alpha-glucosidase, detection of an intron in the 5' untranslated leader sequence, definition of 18 bp polymorphisms, and differences with previous cDNA and amino acid sequences. AB - Acid maltase or acid alpha-glucosidase (GAA) is a lysosomal enzyme that hydrolyzes glycogen to glucose and is deficient in glycogen storage disease type II. Previously, we isolated a partial cDNA (1.9 kb) for human GAA; we have now used this cDNA to isolate and determine sequence in longer cDNAs from four additional independent cDNA libraries. Primer extension studies indicated that the mRNA extended approximately 200 bp 5' of the cDNA sequence obtained. Therefore, we isolated a genomic fragment containing 5' cDNA sequences that overlapped the previous cDNA sequence and extended an additional 24 bp to an initiation codon within a Kozak consensus sequence. The sequence of the genomic clone revealed an intron-exon junction 32 bp 5' to the ATG, indicating that the 5' leader sequence was interrupted by an intron. The remaining 186 bp of 5' untranslated sequence was identified approximately 3 kb upstream. The promoter region upstream from the start site of transcription was GC rich and contained areas of homology to Sp1 binding sites but no identifiable CAAT or TATA box. The combined data gave a nucleotide sequence of 2,856 bp for the coding region from the ATG to a stop codon, predicting a protein of 952 amino acids. The 3' untranslated region contained 555 bp with a polyadenylation signal at 3,385 bp followed by 16 bp prior to a poly(A) tail. This sequence of the GAA coding region differs from that reported by Hoefsloot et al. (1988) in three areas that change a total of 42 amino acids. Direct determination of the amino acid sequence in one of these areas confirmed the nucleotide sequence reported here but also disagreed with the directly determined amino acid sequence reported by Hoefsloot et al. (1988). At two other areas, changes in base pairs predicted new restriction sites that were identified in cDNAs from several independent libraries. The amino acid changes in all three ares increased the homology to rabbit-human isomaltase. Therefore, we believe that our nucleotide sequence for GAA is more precise. We have also identified single base-pair polymorphisms at 18 sites for human GAA, some of which are not silent. PMID- 2111709 TI - Regulation of major histocompatibility complex class-II genes: X, Y and other letters of the alphabet. PMID- 2111710 TI - High-level expression of Bacillus subtilis tryptophanyl-tRNA synthetase in Escherichia coli. AB - The trpS gene encoding Bacillus subtilis tryptophanyl-tRNA synthetase (TrpRS) was prepared from the pUC8-derived pTSQ2 plasmid, mutagenized to introduce an EcoRI site immediately in front of the ATG start codon, and inserted into the pKK223-3 vector downstream to the tac promoter to yield the pKSW1 plasmid. Upon induction with isopropyl-beta-D-thiogalactopyranoside, Escherichia coli JM109[pKSW1] cells synthesized TrpRS to a level corresponding to 45% of total cell proteins. This high level of gene expression facilitates large scale preparation of TrpRS for physical studies, detection of in vivo degradation of mutant forms of TrpRS, and comparative assays of TrpRS by [3H]Trp-tRNA formation and by Trp-hydroxamate formation for the purpose of mutant characterization. Finally, since pKSW1 could complement the temperature-sensitive TrpRS mutation on E. coli trpS 10343 cells, defective mutations of the trpS gene on pKSW1 would be deductible on the basis of complementation testing. PMID- 2111712 TI - The product of rab2, a small GTP binding protein, increases neuronal adhesion, and neurite growth in vitro. AB - The rab genes code for small GTP binding proteins that share with p21ras the ability to bind and hydrolyze GTP. They present significant sequence homologies with the products of YPT1 and SEC4, two small GTP binding proteins involved in the regulation of secretion in the yeast. Several rab genes are expressed in the developing and adult mouse brain. To test directly the possible involvement of these genes in neuronal differentiation, purified rab proteins produced in E. coli were introduced into neurons dissociated from E15 rat midbrain. The most striking effects were obtained with rab2 protein (rab2p). Compared with untreated cells, neurons loaded with rab2p presented an enhanced adhesion to the culture substratum. This phenomenon was visible 3 hr after seeding and was followed within 24 hr by a dramatic increase in neurite growth. Loading the same population of neurons with the products of four other rab genes either decreased neuronal adhesion and neurite growth or had no effect. These experiments suggest that the expression of rab2p plays an important role in neuronal differentiation. PMID- 2111711 TI - Mobilization of arachidonic acid in thrombin-stimulated human platelets. AB - In the present work we investigated the effect of serine esterase inhibitors such as 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC) and phenylmethylsulfonyl fluoride (PMSF), as well as the effect of mepacrine on thrombin-induced mobilization of arachidonic acid (AA) in human platelets. The inhibitor NCDC (0.6 mM) completely abolished the thrombin-induced activation of phospholipase C, phospholipase A2, and transacylase enzymes, whereas the pretreatment of platelets with PMSF (2 mM) resulted in a highly selective inhibition of phospholipase A2 and transacylase activities, with no marked effect on thrombin-induced activation of phospholipase C. The thrombin-induced release of [3H]AA from phosphatidylcholine and phosphatidylinositol was reduced by 90 and 56%, respectively, in the presence of PMSF. This inhibitor also caused a parallel inhibition in the accumulation of [3H]AA (85%) with little effect on thrombin induced formation of [3H]phosphatidic acid (5%), whereas mepacrine (0.4 mM) caused a selective inhibition of phospholipase A2 and transacylase activities with concomitant stimulation of [3H]phosphatidic acid formation in intact human platelets. These results demonstrate that NCDC and PMSF (serine esterase inhibitors) do not affect agonist-induced activation of phospholipases that mobilize arachidonic acid through a common site. Our results further demonstrate that the inhibition of [3H]AA release observed in the presence of NCDC, PMSF, and mepacrine is primarily due to their direct effects on enzyme activities, rather than due to their indirect effects through formation of complexes between inhibitors and membrane phospholipids. Based upon these results, we also conclude that the combined hydrolysis of phosphatidylcholine and phosphatidylinositol by phospholipase A2 serves as a major source for eicosanoid biosynthesis in thrombin stimulated human platelets. PMID- 2111713 TI - Arterial blood gas sampling using a modified standard plastic syringe. AB - A simple modification of the standard plastic syringe is described which converts it into a self-filling system under arterial pressure. This overcomes one of the common errors in arterial blood gas sampling. PMID- 2111714 TI - [Glycogen phosphorylase from human leukocytes. Isolation and kinetic properties]. AB - Homogeneous glycogen phosphorylase from human leukocytes has been obtained. A one step bioluminescent procedure for the enzyme activity assay has been developed. This method is based on a continuous recording of the product of the glycogen phosphorylase-catalyzed reaction using a coimmobilized multienzyme system (phosphoglucomutase, glucose-6-phosphate dehydrogenase, NADH:FMN oxidoreductase and bacterial luciferase). The method sensitivity is 10 times as high compared to earlier described methods. The Km values for glycogen (0.2 mg/ml) and phosphate (3.9 mM) at pH 7.9 were determined. AMP was shown to be the enzyme effector. PMID- 2111715 TI - [Characteristics of kinetics of phospholipid hydrolysis by phospholipase C from Bacillus cereus. Hydrolysis of phosphatidylcholine in the presence of deoxycholate]. AB - Using dynamic light scattering and 31P-NMR spectroscopy methods, the reaction of solubilization of phosphatidylcholine by the ionic detergent, sodium deoxycholate, in aqueous solutions was studied. The kinetics of phosphatidylchodine hydrolysis by phospholipase C from B. cereus depending on the size and structural organization of substrate aggregates was investigated. No phosphatidylcholine hydrolysis was observed in the case of lamellar organization of the substrate, the size of lamellas not exceeding 2000-5000 A. The substrate hydrolysis rate within mixed micelles was controlled by the accessibility of the substrate on the surface of micellar aggregates. There was a decrease in the phosphatidylcholine hydrolysis rate at high detergent concentrations in the system. It was concluded that such a decrease in the hydrolysis rate can be due to two reasons, i) the decrease in mixed micelle size with a simultaneous decrease of surface concentration of the substrate, and, ii) the formation of "pure" detergent micelles capable to adsorb the enzyme by decreasing the "effective" concentration of phospholipase C. PMID- 2111716 TI - [A pH increase in human fibroblast lysosomes during accumulation of non hydrolysable compounds]. AB - The changes in intralysosomal pH were measured in the stationary phase of normal human embryonic fibroblast growth under sucrose loading over a period of 6 to 120 hours and in cells with a typical lysosomal storage pathology, Fabry's disease, using a vital indicator dye, neutral red. It was shown that long-term hypertrophy of the lysosomal compartment during intracellular accumulation of non hydrolysable compounds is concomitant with a pH increase, on the average, by 0.4 units. The highest values of pH (7.0-7.2) were seen in large-sized heterogeneic lysosomes of pathological cells. It is suggested that an increase in intralysosomal pH during accumulation of non-hydrolysable compounds leads to deterioration of conditions that are favourable for the acidic hydrolase function. PMID- 2111717 TI - Parasitism in marine fish after chronic exposure to petroleum hydrocarbons in the laboratory and to the Exxon Valdez oil spill. PMID- 2111718 TI - Effect of sediment contact and uptake mechanisms on accumulation of three chlorinated hydrocarbons in the midge, Chironomus riparius. PMID- 2111719 TI - Concentrations of selected chlorinated pesticides in shrimp collected from the Calcasieu River/Lake Complex, Louisiana. PMID- 2111720 TI - Monitoring cardiopulmonary resuscitation by end tidal carbon dioxide concentration. PMID- 2111721 TI - Who needs long term psychiatric care? PMID- 2111722 TI - Tissue plasminogen activator inhibitor in patients with systemic lupus erythematosus and thrombosis. AB - OBJECTIVE: To examine the relations among tissue plasminogen activator antigen, plasminogen activator inhibitor, the lupus anticoagulant, and anticardiolipin antibodies in patients with systemic lupus erythematosus. DESIGN: Prospective study of blood samples (a) from selected patients with systemic lupus erythematosus whose disease was and was not complicated by a history of thrombosis or recurrent abortions, or both, and (b) from a series of healthy controls with a similar age and sex distribution. SETTING: University based medical clinic. SUBJECTS: 23 Patients with definite systemic lupus erythematosus (American Rheumatism Association criteria), of whom 11 (eight women) aged 26-51 had a history of thrombosis or recurrent abortions, or both, and 12 (10 women) aged 23-53 had no such history. 15 Healthy subjects (10 women) aged 25-58 served as controls. MAIN OUTCOME MEASURES: Tissue plasminogen activator concentrations, plasminogen activator inhibitor activities, detection of the lupus anticoagulant, and values of anticardiolipin antibodies in the two groups of patients and in the patients with a history of thrombosis or abortions compared with controls. Other measurements included concentrations of proteins that are known to change during the acute phase of systemic lupus erythematosus--namely, fibrinogen, C3 and C4, and C reactive protein. RESULTS: Patients with a history of thrombosis or abortions, or both, had significantly higher values of tissue plasminogen activator and plasminogen activator inhibitor than patients with no such history. A significant correlation between tissue plasminogen activator and plasminogen activator inhibitor (r = 0.80) was found only in the patients with a history of complications of their disease. The lupus anticoagulant was detected in six of the 11 patients with a history of thrombosis or abortions when tested by measuring the activated partial thromboplastin time but was found in all 11 patients when tested by measuring the diluted activated partial thromboplastin time. Nine of these 11 patients had raised values of anticardiolipin antibodies. The findings showed no relation to the activity of the disease. CONCLUSIONS: A significant correlation between tissue plasminogen activator concentrations and plasminogen activator inhibitor activities was found only in patients whose systemic lupus erythematosus was complicated by a history of thrombosis or recurrent abortions. The findings show that these patients have raised plasminogen activator inhibitor activities, and the frequent association between these raised activities and the presence of the lupus anticoagulant suggests that the two may be linked. PMID- 2111723 TI - Diabetes in tropical Africa: a prospective study, 1981-7. II. Course and prognosis. AB - OBJECTIVE: To determine the clinical course of diabetes mellitus in tropical Africa. DESIGN: Continuing care and follow up until 31 March 1989 of all newly diagnosed diabetic patients registered at one hospital between 1 June 1981 and 31 May 1987. SETTING: Muhimbili Medical Centre, Dar es Salaam, Tanzania. SUBJECTS: 1250 Newly diagnosed diabetic patients seen over a six year period. 272 (21.8%) Had diabetes requiring insulin, 825 (66.0%) diabetes not requiring insulin, and 153 (12.2%) diabetes of uncertain type. MAIN OUTCOME MEASURES: Survival rates during each year of follow up. RESULTS: 205 (16.4%) Patients were known to have died, 126 (61.5%) in hospital and 79 (38.5%) in the community. At least a further 71 patients were likely to have died. The five year survival rates (95% confidence intervals) for patients with diabetes requiring and not requiring insulin were 71% (62% to 80%) and 84% (80% to 89%) respectively for known deaths and 60% (51% to 69%) and 82% (77% to 86%) respectively for known plus probable deaths. 49 (3.9%) Patients died at the time of presentation. Severe diabetic ketoacidosis and infection were responsible for most deaths in patients with diabetes requiring insulin. Infection was responsible for 24% of deaths in patients with diabetes not requiring insulin and was the main cause of death in the group with uncertain type of diabetes. Cardiovascular and renal causes were responsible for 24% of hospital deaths of patients with diabetes not requiring insulin. Diabetes requiring insulin, young age, and ketonuria at presentation were associated with a significantly worse five year survival on multivariate analysis. On univariate analysis underweight, female sex, low educational background, and manual occupations were additional factors with a worse prognosis. CONCLUSION: Diabetes in sub-Saharan Africa is, in many patients, a serious disease with a poor prognosis. Most deaths, however, are due to preventable causes. More effort is therefore required to increase public awareness of diabetes and to improve patient detection, management, and follow up. PMID- 2111724 TI - In-vitro evaluation of a dual oxygen saturation/hematocrit intravascular fiberoptic catheter. AB - The authors describe the results of an in-vitro evaluation of a prototype new three-fiber intravascular fiberoptic catheter that is suitable for in-vivo measurement of mixed venous oxygen saturation and hematocrit simultaneously. The catheter consists of a single source and two unequally spaced (near and far) detecting fibers. The study showed that the ratio of backscattered light intensities measured at an isobestic wavelength by the two detecting fibers (IRnear/IRfar) can be used as a correcting factor for reducing the dependence of oxygen saturation measurements on hematocrit and also as a means for measuring hematocrit independently. The ability to measure hematocrit in vivo is important in critical care situations where fluids are administered intravenously and blood transfusions are performed routinely. Therefore, the purpose of this study was to investigate the quantitative effect of variations in red blood cell volume induced by changing the pH of the blood. The IRnear/IRfar ratio was found to be affected by variations in bicarbonate ion and carbon dioxide concentrations. The reflected light intensity detected by the catheter was found to be significantly more sensitive to changes in red blood cell volume induced by variations in sodium bicarbonate than to changes induced by variations in carbon dioxide levels in the blood. Clinically, these variations would amount to errors in hematocrit estimations in the order of 2.7%/0.1 pH unit when pH variations are induced by the addition of sodium bicarbonate to the blood and only 0.3%/0.1 pH unit when carbon dioxide is used to vary blood pH. PMID- 2111725 TI - The cost-effectiveness of routine post myocardial infarction exercise stress testing. AB - The cost-effectiveness of the strategy of a routine pre-discharge exercise test (followed by coronary angiography and coronary artery bypass surgery if indicated) in patients with an uncomplicated myocardial infarction was compared with a policy of no routine exercise testing. Using data from the literature, a decision tree was developed to estimate the number of lives saved by the routine exercise test strategy (12 lives saved per 1000 tests), as well as the number of angiograms and coronary artery bypass procedures that would be performed. It was assumed that surgery decreases one year mortality by 25%. The resources consumed by bypass surgery were obtained from a chart review and the costs were estimated using a method of fully allocated costing. Both direct and indirect costs were included. The average cost of coronary artery bypass surgery was $14,958 (1985 Canadian dollars). The cost of routine exercise testing was $255,726 per life saved. With sensitivity analyses this varied from $139,487 (coronary bypass surgery 50% effective) to $1,022,904 (bypass surgery 7.5% effective). A routine post myocardial infarction stress test is an example of how a relatively inexpensive technology, by leading to other expensive clinical actions, can consume a significant amount of resources. PMID- 2111726 TI - HIV transmission to patients with hemophilia by heat-treated, donor-screened factor concentrate. AB - Six hemophilia patients previously seronegative for human immunodeficiency virus (HIV) seroconverted between September 1986 and September 1987. None had risk factors for HIV infection other than hemophilia. We compared the factor concentrates received by these patients with the concentrates received by 10 seronegative hemophilia patients. A statistically significant association was observed between seropositivity and the receipt of two lots of Factor VIII produced from the same plasma pool (odds ratio 77, p = 0.0014); five of the six case subjects but none of the control subjects had received concentrate from one of the two lots. Available evidence suggests that the sixth case subject had also received concentrate from an implicated lot. Symptoms including rash and fever were reported in five cases within 6 weeks after the implicated concentrate had been given. The implicated lots were produced from plasma from paid donors that had been screened and then heated at 60 degrees C for 30 hours in the lyophilized state. Subsequent to our investigation all concentrate produced by this process was removed from distribution. PMID- 2111727 TI - Tracking the cost of health care: the bill came to $5339. PMID- 2111728 TI - A mammary stimulating mitogen(s) from rat muscle: its possible influence in mammary tumorigenesis. AB - A mitogen has been shown to be present in rat abdominal muscle tissue, which could stimulate rat mammary cells grown in culture. Studies on the in vivo stimulatory effects on the rat mammary gland, taking increase in DNA synthesis, mitotic index and wholemount preparation as the parameters, affirmed the presence of a mammary stimulating factor in the muscle tissue. Treatment of rat mammary glands with the crude mitogen preparation before and after a single gastric dose of 9,10-dimethyl-1,2-benzanthracene (DMBA), increased the mammary tumor incidence suggesting its possible influence in carcinogen-induced tumorigenesis in rats. PMID- 2111729 TI - Effects of beta-carotene on chemically-induced skin tumors in HRA/Skh hairless mice. AB - In order to evaluate the role of beta-carotene as an inhibitor of skin carcinogenesis, hairless female HRA/Skh mice were treated with the initiator 7,12 dimethylbenz[a]anthracene (DMBA) and with the promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), and were fed a balanced diet free from vitamin A either with or without gavage-administered beta-carotene. There was no evidence of avitaminosis A or differences in body weight in mice deprived of beta-carotene and vitamin A, compared with those given 290 or 1430 IU beta-carotene/kg per day. Mice fed with normal animal feed pellets displayed a significantly higher body weight (28.5 +/- 1.95 g) compared with mice on the special diet (25.7 +/- 1.9 g), and also displayed a higher papilloma yield. However animals on the special diet, fed with beta-carotene from weaning, displayed significantly lower numbers of papillomas per mouse. This lower papilloma yield was evident particularly between 12-24 weeks after commencement of the study, which coincided with the period of maximum tumor yield in DMBA/TPA-treated mice. The characteristic regression of papillomas after that time points to the reversibility of many earlier papillomas, and their dependence on continued TPA administration. Evaluation of carcinomas in mice on the various dietary regimes showed there was no significant difference between any group, including those fed with beta-carotene continuously from weaning. The present results demonstrate that a sustained dietary intake of beta-carotene from 3 weeks of age partially suppressed the growth of papillomas, but did not affect the course of malignant progression in DMBA/TPA-treated HRA/Skh mice. It is evident that beta-carotene predominantly affects TPA-dependent papillomas, which possess reversible properties and have a low probability of progression to form carcinomas. PMID- 2111730 TI - [Surgical treatment of Zenker's diverticulum]. AB - The authors present an account of diagnostic methods, endoscopic problems and surgical treatment of Zenker's diverticula of the oesophagus. They analyze possibilities of X-ray and endoscopic diagnosis; a frequent problem is the insertion of an oesophageal probe before operation; tamponade of the diverticula before operation is useful. Surgical treatment is indicated in major diverticula, small flat ones are followed up. The surgical approach is from the left side of the neck. In the authors' department always total resection of the dicerticulum was performed in major diverticule, invagination could be used in minor diverticula. Early and late complications of operations are discussed. PMID- 2111731 TI - Addition of telomere-associated HeT DNA sequences "heals" broken chromosome ends in Drosophila. AB - Stocks of D. melanogaster X chromosomes carrying terminal deletions (RT chromosomes) have been maintained for several years. Some of the chromosomes are slowly losing DNA from the broken ends (as expected if replication is incomplete) and show no telomere-associated DNA added to the receding ends. Two stocks carry chromosomes that have become "healed" and are no longer losing DNA. In both stocks the broken chromosome end has acquired a segment of HeT DNA, a family of complex repeats found only at telomeres and in pericentric heterochromatin. Although the HeT family is complex, the HeT sequence joined to the broken chromosome end is the same in both stocks. In contrast, the two chromosomes are broken in different places and have no detectable sequence similarity at the junction with the new DNA. Sequence analysis suggests that the new telomere sequences have been added by a specific mechanism that does not involve homologous recombination. PMID- 2111732 TI - In vivo degradation of a transcriptional regulator: the yeast alpha 2 repressor. AB - Metabolic instability is characteristic of regulatory proteins whose in vivo concentrations must vary as a function of time. The cell type-specific alpha 2 repressor of the yeast S. cerevisiae is shown here to have a half-life of only approximately 5 min. Each of the two structural domains of alpha 2 carries a sequence that can independently target a normally long-lived protein for rapid destruction. Moreover, these two degradation signals are shown to operate via distinct mechanisms. Mutants deficient in the degradation of alpha 2 have been isolated and found to have a number of additional defects, indicating that the pathways responsible for alpha 2 turnover include components with multiple functions. Finally, we demonstrate that a short-lived subunit of an oligomeric protein can be degraded in vivo without destabilizing other, long-lived subunits of the same protein. This subunit-specific degradation makes possible a novel type of posttranslational remodeling in which a heteromeric protein could be functionally modified by selective, degradation-mediated replacement of its subunits. PMID- 2111733 TI - SNAPs, a family of NSF attachment proteins involved in intracellular membrane fusion in animals and yeast. AB - Three new and likely related components of the cellular fusion machinery have been purified from bovine brain cytosol, termed alpha-SNAP (35 kd), beta-SNAP (36 kd), and gamma-SNAP (39 kd). Transport between cisternae of the Golgi complex measured in vitro requires SNAP activity during the membrane fusion stage, and each SNAP is capable of binding the general cellular fusion protein NSF to Golgi membranes. The SNAP-NSF-membrane complex may be an early stage in the assembly of a proposed multisubunit "fusion machine" on the target membrane. SNAP transport factor activity is also found in yeast. Yeast cytosol prepared from a secretion mutant defective in export from the endoplasmic reticulum (sec17) lacks SNAP activity, which can be restored in vitro by the addition of pure alpha-SNAP, but not beta- or gamma-SNAPs. These data suggest that the mechanism of action of SNAPs in membrane fusion is conserved in evolution. PMID- 2111734 TI - PrlA (SecY) and PrlG (SecE) interact directly and function sequentially during protein translocation in E. coli. AB - Three strategies for genetic analysis show that two inner membrane components of the export machinery, PrlA (SecY) and PrlG (SecE), interact directly while catalyzing the translocation of secreted proteins across the cytoplasmic membrane of E. coli. The first, suppressor-directed inactivation (SDI), exploits the specific interaction between dominant prl suppressors of signal sequence mutations and mutant LacZ hybrid proteins. The second, Sec titration, extends SDI to allow the identification of various Sec proteins that are present in the translocation complex. The third uses the synthetic lethality of certain double mutant strains to infer physical interactions between gene products. Biochemical data obtained with SDI strains allow the identification of two different secretory intermediates and indicate that PrlG functions before PrlA in the secretion pathway. PMID- 2111735 TI - Epigenetic control of transgene expression and imprinting by genotype-specific modifiers. AB - Expression and DNA methylation of the transgene locus TKZ751 are controlled by genotype-specific modifier genes. The DBA/2 and 129 genetic backgrounds enhanced expression, while the BALB/c background suppressed expression, but only following maternal inheritance of the BALB/c modifier. Epigenetic modification of the transgene locus was cumulative over successive generations, which in BALB/c mice resulted in an irreversible methylation after three consecutive germline passages. Therefore, at the TKZ751 locus the germline fails to reverse previously acquired epigenetic modifications, a process that is usually essential to restore the genomic totipotency. Hence the genotype-specific modifier genes regulate penetrance and expressivity as well as parental imprinting of the TKZ751 locus through epigenetic modification. PMID- 2111736 TI - Increased production of reactive oxygen species by cells from mice acutely infected with Trypanosoma cruzi. AB - Release of reactive oxygen species (ROS) by cells from BALB/c mice was studied during the acute stage of the infection with 50 bloodstream forms of Trypanosoma cruzi, Tulahuen strain. Production of ROS by spleen and peritoneal cells was evaluated by chemiluminescence using luminol as enhancer (CL-Lum). Three to four weeks after infection, CL-Lum response after the addition of opsonized zymosan to spleen and peritoneal cells from infected mice was 13 and 98 times, respectively, above the levels obtained with cells from noninfected mice. The kinetics of this hyperactivity was similar to that of the parasitemia. Both reached maximal values on the third to fourth weeks and decreased at 7 weeks postinfection. During this hyperactivation stage, spleen and peritoneal cells from infected mice showed a "spontaneous" CL-Lum response (without any stimulus added in vitro) absent in noninfected mice. Both, "spontaneous" and zymosan stimulated CL-Lum responses were inhibited by 100 microM azide and by 0.8 microM superoxide dismutase, suggesting the involvement of hemoproteins and superoxide anion in the measured responses. Moreover, spleen cells from acutely infected mice displayed a hyperactivity in the CL-Lum response when recombinant interferon-gamma was added in vitro. Supernatants of spleen cells from both normal or infected mice, stimulated in vitro with concanavalin A, contained similar levels of interferon and were equally able to stimulate the trypanocidal activity of normal macrophages. These results suggest that mediators of activation of phagocytic cells can be produced during acute T. cruzi infection. In addition, phagocytic cells from acutely infected mice were activated in vivo and were hyperactive to the in vitro stimulation. PMID- 2111737 TI - High-affinity receptors for interleukin-2 are not required for the induction of human unstimulated B lymphocyte differentiation by this lymphokine. AB - We have reported that one of the currently known receptors for interleukin-2 (IL 2), the p70 protein, is constitutively expressed on resting T lymphocyte membrane. We demonstrated that exposure of these cells to high concentrations of IL-2 resulted in the transcription of genes whose expression occurred early during cell activation such as cmyc, cmyb protooncogenes, and the Tac gene itself. IL-2 is thought to exert its biological effects by binding to its high affinity receptors on cell membrane. Recent studies using B cell lines emphasized that within the high-affinity receptor complexes, p55 serves to allow high affinity binding, and p70, to transduce signals. In this study, we prepared human unstimulated B cells devoid of detectable Tac antigen, and consequently, of the high-affinity receptor complexes. We designed experiments such that no in vitro de novo expressed receptors, if any, could interact with IL-2, so that any biologic events triggered by IL-2 must have been mediated in the absence of the high-affinity receptors. Under these conditions, we demonstrated that a short and unique exposure (1 hr) of these cells to high concentrations (5 nM) of IL-2 allowed its binding to cell membrane and resulted in a competent signal leading to the generation of a majority of 25S Tac mRNA, and a progression signal allowing B cell terminal differentiation into plasma cells. PMID- 2111738 TI - Antibacterial resistance induced by recombinant interleukin 1 in myelosuppressed mice: effect of treatment schedule and correlation with colony-stimulating activity in the bloodstream. AB - We have investigated the effects of interleukin 1 (IL-1) administration on the ability of neutropenic mice to resist Pseudomonas aeruginosa challenge in vivo. Cyclophosphamide-treated mice received human rIL-1 beta at 7.0, 0.7, or 00.7 micrograms/kg, according to different regimens, to be challenged with a lethal ip inoculum of pseudomonas cells 5 days after myelosuppression. The repeated exposure of the neutropenic mice to an overall cytokine dosage of 7.0 or 0.7 micrograms/kg during the 4 days after myelosuppression was found to optimally restore the animals' antibacterial resistance. However, when administered as a single injection 24 hr before challenge, the same dosages of IL-1 had lower or no effect in enhancing survival, primarily leading only to a reduction in the amount of antipseudomonal chemotherapy required for cure. The regimen of IL-1 administration conferring optimal protection also resulted in a decrease in the number of pseudomonas cells recovered from the peritoneal cavity of infected mice. This regimen accelerated hematopoietic recovery in cyclophosphamide-treated mice. Assay of serum colony-stimulating activity (CSA) revealed that (a) cyclophosphamide treatment alone significantly increased the level of circulating CSA, (b) administration of a single dose of IL-1 to neutropenic mice induced an early, further increase in serum CSA, followed by depression, (c) a biphasic pattern of CSA response was also evident in mice repeatedly treated with IL-1. These results suggest that regulation of hematopoiesis may have an important role in the induction of antibacterial resistance in myelosuppressed hosts repeatedly treated with low dosages of IL-1. PMID- 2111739 TI - Protective role of intracoronary fatty acid binding protein in ischemic and reperfused myocardium. AB - In this study, fatty acid binding protein was used to protect an ischemic heart from reperfusion injury. Isolated rat heart was preperfused in the presence of 1.4 microM liposome-bound fatty acid binding protein for 15 minutes, followed by 30 minutes of ischemia and 30 minutes of reperfusion. Our results indicated better preservation of myocardial high-energy phosphate compounds (including ATP and creatine phosphate), reduced creatine kinase and lactate dehydrogenase release from the heart, and improved coronary flow in hearts treated with fatty acid binding protein compared with untreated controls. Fatty acid binding protein enhanced reacylation of arachidonic acid into phospholipids, thereby preserving membrane phospholipids and reducing free fatty acid contents during ischemia and reperfusion. In addition, fatty acid binding protein-bound long-chain free fatty acids and their thioesters as well as carnitine esters were increased in the cytosolic compartment of the heart. These results suggest that fatty acid binding protein may be used as a possible therapeutic agent to improve myocardial function during reperfusion of ischemic heart. PMID- 2111740 TI - Does endocardial endothelium mediate positive inotropic response to angiotensin I and angiotensin II? AB - The positive inotropic response to angiotensin I and II in cardiac tissue of most mammalian species, as well as the exact site in the heart for conversion of local and systemic angiotensin I into angiotensin II, remains to be elucidated. In isolated cat papillary muscles, angiotensin I and angiotensin II (0.1 nM to 1 microM, 35 degrees C, 1.25 mM Ca2+) increased, in a dose-dependent manner, peak twitch tension with typical slight prolongation of twitch duration. This typical response did not necessitate the presence of an intact endocardial endothelium (EE), as a similar response was observed in muscles where the EE had been damaged by a 1-second exposure to 0.5% Triton X-100. After addition of captopril, an angiotensin converting enzyme inhibitor, the positive inotropic response to angiotensin I was completely abolished, both in the presence and the absence of an intact EE. Hence, the heart possesses angiotensin converting enzyme, which mediates the positive inotropic response to angiotensin I. An intact EE was not a prerequisite for this response; thus, myocytes as well as nonmyocytes may be possible locations (in addition to the EE) for angiotensin converting enzyme. In the presence of an intact EE, and after addition of captopril, the positive inotropic response to angiotensin II was significantly diminished (desensitization). By contrast, in the absence of an intact EE, but also after addition of captopril, the positive response to angiotensin II was potentiated (sensitization). Both desensitization and sensitization (in the presence or absence of an intact EE, respectively) of the response to angiotensin II induced by the addition of captopril were inhibited by indomethacin, a cyclooxygenase inhibitor, suggesting a role for prostaglandins. PMID- 2111741 TI - Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris. AB - To investigate the prostaglandin I2 (PGI2) half-life regulated by high density lipoprotein (HDL) in patients with coronary artery disease (CAD), we determined the stability of PGI2 and serum apolipoprotein A-I (Apo A-I) and apolipoprotein A II (Apo A-II) levels in four age-matched groups of patients: controls (n = 17), angina pectoris (n = 18), unstable angina pectoris (n = 17), myocardial infarction (n = 19) (acute phase, 3.6 +/- 1.7 hours from onset; subacute phase, 75 +/- 15 hours from onset in the same patients). Serum PGI2 half-life and total serum Apo A-I levels were lower in the CAD group than in the control group. PGI2 was least stable in patients with unstable angina and the acute phase of myocardial infarction. In these patients, the molar ratio of Apo A-I to Apo A-II and HDL-associated Apo A-I levels were decreased, and free Apo A-I levels were increased. After in vitro incubation of HDL with increasing amounts of Apo A-II, Apo A-I in HDL was displaced by Apo A-II, with the parallel decrease in stability of PGI2. Free Apo A-I cannot stabilize PGI2. HDL-associated Apo A-I, whose amount is affected by Apo A-II, stabilized PGI2 and correlated well with stability of PGI2 in patients with CAD and control patients. Decreased PGI2 half-life may play an important role in the pathogenesis of atherosclerosis and thrombus formation in the coronary arteries, especially thrombus formation during an acute coronary event. PMID- 2111742 TI - Quantitation of venous clot lysis with the D-dimer immunoassay during fibrinolytic therapy requires correction for soluble fibrin degradation. AB - Plasma cross-linked fibrin-degradation products were analyzed using a D-dimer (DD) immunoassay in patients with deep vein thrombosis (DVT) or acute myocardial infarction (MI) treated with fibrinolytic therapy, and the results were correlated with clot lysis documented angiographically. In 13 patients with DVT, the mean DD concentration increased 10-fold (1,074 +/- 252 to 10,333 +/- 1,004 ng/ml) during therapy, but neither the peak level nor the DD concentration integrated over the course of therapy correlated with clot lysis. Since plasma DD can derive from degradation of soluble plasma fibrin as well as from thrombi, the contribution of the former was estimated by in vitro incubation of the pretreatment plasma with plasminogen activator. Subtraction of this value from the measured posttreatment DD concentration provided a "corrected" level that represented DD originating from lysis of thrombi. This modification resulted in improved correlation of DD levels with clot lysis. The mean corrected peak DD was higher in patients with successful thrombolysis (8,780 +/- 1,352 ng/ml) compared with patients without lysis (3,075 +/- 589 ng/ml, p less than 0.001). There was a moderate correlation between the volume of clot lysed and the corrected peak DD (r = 0.62) and a higher correlation with the corrected DD integrated over the course of treatment (r = 0.97). By contrast, the corrected DD concentrations were near zero in patients treated for MI with or without thrombolytic reperfusion, suggesting that fibrin in small coronary thrombi did not contribute significantly to total plasma DD during therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111743 TI - Endothelial modulation of the coronary vasculature in vessels perfused via mature collaterals. AB - Previous in vivo studies have shown that vasopressin, which releases the endothelium-derived relaxing factor and constricts coronary smooth muscle, produces augmented constriction of coronary microvessels perfused by mature collaterals. We hypothesized that chronic perfusion through collaterals produces endothelial dysfunction in the recipient vasculature. Mature collaterals were stimulated in mongrel dogs by the ameroid constrictor technique. After 3-6 months, rings of conduit vessels (obtuse marginals) were studied in organ chambers, and coronary microvessels (100-220 microns) were studied in a pressurized, no-flow state with a microvessel imaging apparatus. Eleven dogs were used as controls. Large vessels were preconstricted with prostaglandin F2 alpha to 30-70% of the maximum potassium chloride tension, and microvessels were preconstricted to 20-60% of the baseline diameter with the thromboxane mimetic U46619. Relaxations to the receptor-mediated agents acetylcholine and ADP were markedly impaired in collateral-dependent coronary microvessels, whereas relaxations to nitroglycerin were enhanced compared with microvessels from control dogs. Relaxation to the calcium ionophore A23187, which releases the endothelium-derived relaxing factor through nonreceptor-mediated mechanisms, were similar in control and ameroid microvessels. Constriction to vasopressin was augmented in collateral-dependent microvessels compared with controls. Responses to all agonists were similar between control and collateral-dependent large vascular rings. In conclusion, chronic perfusion through collateral vessels selectively impairs receptor-mediated endothelium-dependent relaxations and augments constriction to vasopressin in the coronary microcirculation. These findings may have important implications regarding neurohumoral regulation of perfusion to collateral-dependent myocardium. PMID- 2111744 TI - Conjugation to antifibrin Fab' enhances fibrinolytic potency of single-chain urokinase plasminogen activator. AB - Single-chain urokinase plasminogen activator (scu-PA) that had been modified with N-succinimidyl-3-(2-pyridyldithio)propionate was covalently linked by disulfide bonds to the Fab' of a monoclonal antibody specific for the beta-chain of fibrin (antibody 59D8). scu-PA-59D8 Fab' conjugate was separated from free scu-PA and two-chain urokinase coupled to 59D8 Fab' by two-step affinity chromatography. First, the reaction mixture was chromatographed on a column containing Sepharose linked to the peptide that had been used as immunogen for antibody 59D8; scu-PA 59D8 Fab' conjugate and unconjugated 59D8 Fab' were retained but not unconjugated scu-PA. Then, the eluate from the peptide-Sepharose column was chromatographed on a column containing Sepharose linked to benzamidine, which acts as a ligand for two-chain urokinase. The molecular weight of the scu-PA-59D8 Fab' conjugate was approximately 100 kDa when electrophoresed on a nonreducing sodium dodecylsulfate polyacrylamide gel. Enzymatic assay after purification revealed that more than 97% of the scu-PA present in the conjugate retained the single-chain form. The Fab' portion of the conjugate functioned in a manner indistinguishable from that of native antibody 59D8. In an in vitro assay for lysis of fibrin monomer, the fibrinolytic potency of scu-PA-59D8 Fab' was 33-fold more than that of tissue plasminogen activator (p less than 0.001), 230-fold more than that of unconjugated scu-PA (p less than 0.0001), and 420-fold more than that of urokinase (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111745 TI - Prostacyclin, high density lipoproteins, and myocardial ischemia. PMID- 2111746 TI - Successful treatment by chemotherapy for acromegaly associated with ectopic growth hormone releasing hormone secretion from a carcinoid tumour. AB - Acromegaly secondary to the secretion of ectopic growth hormone releasing hormone (GHRH) is rare. We have documented the presentation and unusual clinical course of a patient with a disseminated GHRH-secreting bronchial carcinoid tumour associated with acromegaly over a 17-year period. Recurrent widespread metastatic lesions have been treated over a 10-year period by repeated cycles of the nitrosourea CCNU and 5-fluorouracil with evidence of tumour regression and reduction of circulating growth hormone (GH) and urinary 5HIAA excretion. This cytotoxic regimen, which has been well tolerated, may prove valuable in the management of disseminated carcinoid tumours. PMID- 2111747 TI - Impaired secretion of parathyroid hormone in patients with rheumatoid arthritis: relationship to inflammatory activity. AB - Hypocalcaemic tests, employing infusion of EDTA over 1 h, were performed in 22 patients with rheumatoid arthritis (RA) and 14 healthy controls. The basal levels of calcium and parathyroid hormone (PTH) were not significantly different in the two groups. The RA patients displayed a markedly impaired PTH response during infusion of EDTA compared with the controls although the reduction of plasma ionized calcium was similar. The PTH response was furthermore significantly, inversely, related to the inflammatory activity measured as sedimentation rate (r = 0.65; P less than 0.01), i.e. the more pronounced the inflammation, the less the capacity to secrete PTH. Since secretion of PTH is related to the intracellular calcium concentration of the parathyroid cells, these findings are in line with previous observations of a higher intracellular calcium content in inflammatory disease. They also support the earlier indications of reduced bone turnover in inflammatory arthritides. An insufficient parathyroid function could be one factor contributing to bone disease in these conditions. PMID- 2111748 TI - Isolated hypogonadotrophic hypogonadism: a family with autosomal dominant inheritance. AB - A family is reported in which isolated hypogonadotrophic hypogonadism is inherited as an autosomal dominant condition with variable expression. In previous familial cases, inheritance was autosomal recessive. Comparison is made with the endocrine and genetic findings in Kallmann's syndrome, which should be considered a separate disorder. There is difficulty in drawing a sharp distinction between hypogonadotrophic hypogonadism and constitutional delay in puberty in this family. PMID- 2111749 TI - Pharmacokinetics of nitroglycerin and its dinitrate metabolites over a thirtyfold range of oral doses. AB - The pharmacokinetics of nitroglycerin and the formation of its dinitrate metabolites (1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate) were determined in six healthy volunteers after administration of six oral solution doses ranging from 0.4 mg to 13 mg. ANOVA analysis indicated significant differences between subjects for all Cmax/dose and AUC/dose measurements. No significant difference between doses were noted for these parameters except for AUC/dose for 1,3 glyceryl dinitrate. The ratio of metabolites (1,2-metabolite/1,3-metabolite) for the 0.4 mg dose was significantly different from the ratios for the doses of 1.6 mg or higher. Measurements of the combined residence time parameter suggest nonlinearity in nitroglycerin absorption and metabolism processes of AUMC/AUC between the 0.4 and the 13 mg doses. Consistent results were observed in the AUC ratios of metabolites for 0.4 mg doses of nitroglycerin between oral and sublingual administrations, suggesting that the increased metabolite ratio noted for sublingual nitroglycerin may reflect differences in dose, rather than differences in route of administration. PMID- 2111750 TI - Altered disposition of fleroxacin in patients with cystic fibrosis. AB - Thirteen patients with cystic fibrosis and 12 healthy control volunteers received a single oral 800 mg dose of fleroxacin and 800 mg every day for 5 days. Interstitial fluid penetration was studied by the suction-induced blister technique. Fleroxacin and its two major metabolites, N-demethyl and N-oxide, were analyzed in plasma and urine by HPLC. Single-dose absorption parameters (absorption rate constant, normalized peak plasma drug concentration, and time to reach peak concentration) and total urinary excretion indicated that fleroxacin was absorbed more slowly and more completely in patients with cystic fibrosis than in control subjects. Fleroxacin volume of distribution tended to be smaller in patients with cystic fibrosis and it reached statistical significance after a single dose when normalization for lean body mass was applied. When normalized for lean body mass, the formation clearance of N-demethyl fleroxacin and N-oxide fleroxacin was significantly greater in patients with cystic fibrosis than in control subjects (p less than 0.05). These data concur with those of others showing an induction of drug-metabolizing enzymes in cystic fibrosis. Renal clearances of fleroxacin and its metabolites were significantly increased in cystic fibrosis (p less than 0.05), and this seems to be explained by a decreased tubular reabsorption of these compounds. The differences seen in the pharmacokinetics of fleroxacin in cystic fibrosis support the theories of generalized induction of drug metabolism and of a defective renal tubular reabsorptive process of drugs in cystic fibrosis. PMID- 2111751 TI - Pharmacokinetics of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine in patients with severe human immunodeficiency virus infection. AB - This article describes the pharmacokinetics of 2',3'-dideoxyadenosine (ddA) and 2',3'-dideoxyinosine (ddI) as determined during phase I clinical trials in patients with acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex. Drug levels were determined by HPLC in plasma, cerebrospinal fluid, and urine after administration of the drugs either intravenously or as an oral liquid given with antacid. ddA was metabolized rapidly and quantitatively to ddI to such an extent that ddA was undetectable in the plasma even during continuous intravenous administration of ddA. The plasma kinetics of ddI were generally monoexponential and were characterized by a half life of 38 minutes. This probably does not accurately reflect the kinetics of the active species of ddI, which appears to be 2',3'-dideoxyadenosine triphosphate, formed intracellularly. Oral bioavailability was 38% for oral liquid given with antacid. The total body clearance averaged 1.00 L/kg/hr, with a volume of distribution of 1.01 L/kg. Approximately 36% of the intravenous dose could be recovered unchanged in the urine. The level of ddI in the cerebrospinal fluid 1 hour after drug infusion averaged 21% of that of the simultaneous plasma level. It is concluded that ddI has pharmacokinetic properties that are amenable to its clinical use. PMID- 2111752 TI - The chloride shift may facilitate oxygen loading and unloading to/from the hemoglobin from the brown bear (Ursus arctos L.). AB - 1. The oxygen binding properties of hemolyzed bear blood were studied in 0.1 M Tris and 0.1 M Hepes buffer with respect to the possible effects of temperature, pH, pCO2, 2,3-DPG, and chloride ions. 2. There was a significant Bohr shift with a Bohr factor (delta log P50/delta pH) of the magnitude of -0.5. The temperature sensitivity expressed by the apparent heat of oxygenation minus the heat of oxygen in solution was about -8.1 kcal/mol at pH 7.4. 3. Chloride ions decreased the oxygen affinity in the concentration range 50-200 mM, and there was a marked increase in the co-operativity of oxygenation up to a chloride concentration of about 200 mM. 4. There were no effects of pCO2 and 2,3-DPG in the presence of 200 mM Cl-, while in the absence of Cl-, 2,3-DPG had the same effect as 200 mM Cl- at 37 degrees C and pH 7.4. 5. Our results suggests at least two different binding sites for the chloride ion, one high affinity site which may also bind 2,3-DPG in the absence of chloride, and one or more low affinity sites, which only binds chloride. 6. The results further show, that a chloride shift of about 33 mM may account for as much as a 40% increase in O2 unloading, without taking into account the additional effect of the Bohr shift. PMID- 2111753 TI - Venous hypercarbia associated with severe sepsis and systemic hypoperfusion. AB - We studied 37 patients with severe sepsis and systemic hypoperfusion to assess changes in PvCO2. Before fluid administration, the cardiac index (CI) was 2.64 +/ 0.14 L/min.m2. The PvCO2 was 38 +/- 1 torr and mixed venous pH was 7.32 +/- 0.02. The venous-arterial CO2 tension gradient (P[v-a]CO2) was 6 +/- 1 torr. After fluid administration, the CI increased to 3.45 +/- 0.14 L/min.m2 (p less than .001) and the P(v-a)CO2 decreased to 5 +/- 1 torr. The correlation between the change in CI and the change in P(v-a)CO2 was r = .42, p less than .01. P(v a)CO2 was elevated in 19 (51%) patients before fluid administration (P[v-a]CO2 greater than 6 torr) (hypercarbic group). The P(v-a)CO2 gradient in this group was 9 +/- 1 compared with 4 +/- 1 torr in 18 patients with a normal P(v-a)CO2 gradient (p less than .001) (normocarbic group). PvCO2 was 41 +/- 2 torr in the hypercarbic group compared with 35 +/- 2 torr in the normocarbic group (p less than .05). No difference was noted in PaCO2. Venous arterial pH and HCO3- gradients were of greater magnitude in the hypercarbic group, -0.05 +/- 0.003 and 2.4 +/- 0.3 mEq/L compared to -0.02 +/- 0.004 (p less than .001) and 1.1 +/- 0.2 mEq/L (p less than .001), respectively. CI in the hypercarbic group was 2.3 +/- 0.2 compared to 3.0 +/- 0.2 L/min.m2 in the normocarbic group (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111754 TI - Effect of single dose surfactant on pulmonary function. AB - Sequential changes in pulmonary mechanics in response to single dose exogenous surfactant instillation were studied in 15 preterm neonates who had hyaline membrane disease (HMD). The infants were part of a larger double-blind national study. Birth weight ranged from 0.88 to 1.55 kg, and gestational age was between 27 to 32 wk. There were six infants in the surfactant group and nine in the placebo group. Pulmonary mechanics were studied before and at 2, 24, 60, and 96 h after surfactant or sham instillation using a pneumotachometer and an esophageal balloon catheter. The variables studied were dynamic compliance (Cdyn), pulmonary resistance, work of breathing, tidal volume, and minute ventilation. Infants in the surfactant group showed an immediate and significant (p less than .05) improvement in gas exchange ratio, decreased mean airway pressure (9.7 +/- 0.9 to 7.9 +/- 0.4 cm H2O) and airway resistance (133 +/- 6.3 to 92 +/- 14.9 cm H2O/L.sec) (p less than .05). Changes in Cdyn were noted only at 24 h after surfactant instillation. In the control group, gradual improvement occurred after the initial deterioration. The findings suggest that the immediate improvement in oxygenation after surfactant instillation is the result of factors other than changes in lung compliance, such as improved ventilation/perfusion and better capillary stability with decreased leakage of fluid into alveoli. PMID- 2111755 TI - Enteral nutrients prevent stress ulceration and increase intragastric volume. AB - Tube feedings and intragastric glucose prevent stress ulceration by unknown mechanisms. We tested the hypothesis that glucose protects the gastric mucosa by direct repletion of glycogen stores. We compared the effects of enteral glucose with enteral lipids in the rat restraint model. The rats were given equal volumes of 0.9% saline, 20% lipids, or 25% glucose during a 4-h period of restraint stress. The effects of each treatment on gastric residual volume and luminal pH, as well as on stress lesion formation were measured. Both enteral nutrients significantly reduced the number of mucosal lesions compared to saline. In conjunction with their protective effect, both nutrients significantly increased both gastric residual volume and luminal pH. As stress-induced prolonged gastric contractions are related to mucosal injury in this model, the nutrient solutions may have been protective in part because they increased gastric volume and prevented mechanical trauma to the mucosa. We conclude that tube feedings do not prevent stress ulceration by glucose's repletion of local glycogen stores, as lipids and glucose were equally effective. Both increased intragastric volume and increased intraluminal pH associated with administration of enteral nutrients may contribute to their protection of the gastric mucosa from stress ulceration. PMID- 2111756 TI - Ketamine in hypovolemic dogs. AB - The cardiopulmonary consequences of hemorrhagic hypovolemia and the subsequent administration of ketamine were evaluated in eight dogs; five additional dogs served as controls. Heart rate (HR), systemic vascular resistance, breathing rate, minute ventilation (VE), PaO2, alveolar-arterial oxygen tension gradient, and oxygen extraction ratio increased, while arterial and pulmonary pressures, CVP, cardiac output, oxygen transport, PVO2 PaCO2, mixed venous oxygen content, bicarbonate, and base deficit decreased in response to hypovolemia. Ketamine administration was associated with a significant increase in HR, arterial and pulmonary BP, and PaCO2, and a significant decrease in VE (transient), PaO2 (transient), and pH. Ketamine supported cardiovascular function well, did not impair tissue oxygenation, and caused only transient respiratory depression in these hypovolemic dogs. PMID- 2111757 TI - Evaluation of metabolic measuring instruments for use in critically ill patients. AB - We evaluated three commercial indirect calorimetry devices which are used during artificial ventilation. Commercial butane, which had an RQ of 0.615, consumes 6.40 ml oxygen, and produces 3.94 ml CO2/1 ml, was burned in a gas-tight combustion chamber in conjunction with the ventilation of a lung model. During combustion, the flow rate of butane was measured with a soapfilm flowmeter for the calculation of reference values of oxygen consumption (VO2) and CO2 production (VCO2). To investigate the effect of oxygen concentration on the accuracy of these instruments, measurements were carried out at FIO2 values of 0.3, 0.4, 0.5, and 0.6 with a fixed ventilation mode (tidal volume 500 ml; respiratory rate 16 breath/min, intermittent positive-pressure ventilation). For the Datex Deltratrac Metabolic Monitor, the mean relative errors of measured VO2, VCO2, and RQ were all within 4.0%, 2.9%, and 4.0%, respectively. For the Engstrom Metabolic Computer, the corresponding values were 1.4%, 5.7%, and 6.0%, and for the SensorMedics MMC Horizon, 5.7%, 2.9%, and 5.9%. PMID- 2111758 TI - The patient with refractory genital warts in the STD-clinic. Treatment failure with CO2-laser. AB - Sixty two patients with refractory genital warts attending a VD-clinic were treated with CO2-laser. Residual warts or new wart formation was observed in 45 of them (72%), two weeks after operation, resulting in an immediate cure rate of 27%. The cure rate obtained was independent of location, duration, and previous treatment of warts. Reoperation with CO2-laser was performed in 12 patients, and all had remaining lesions two weeks after operation. It is concluded that a single CO2-laser treatment often is an insufficient procedure for eradication of disseminated refractory genital warts. PMID- 2111759 TI - [Transcranial Doppler curve analysis. On the pathophysiology of unilateral carotid stenoses]. AB - Vascular reactivity to changes in arterial CO2 content can be measured by analysis of Doppler curves in the middle cerebral artery (MCA). Vascular reactivity indicates the capability of the cerebrum of controlling peripheral resistance. In patients with threatening cerebrovascular disease (CVD) vascular autoregulation may be reduced. The circle of Willis plays a central role in the pathophysiology of unilateral high-grade ICA-stenosis. Previous classification of the degree of stenosis or of the clinical stage does not allow to describe the actual pathophysiology or prognosis of CVD sufficiently. PMID- 2111760 TI - Evaluation of immunocytochemical detection methods of incorporated bromodeoxyuridine in hybridomas. AB - Bivariate distributions obtained from nominal acid hydrolysis or thermal treatment methods used in the cell cycle analysis of incorporated bromodeoxyuridine were shown to be unacceptable with hybridomas. Four different cell treatment and staining methods were compared. These methods are acid hydrolysis, thermal denaturation, nuclei extraction with pepsin digestion, and simultaneous pepsin digestion and acid hydrolysis. The nuclei extraction method was determined to be the most appropriate for the immunocytochemical staining of incorporated bromodeoxyuridine in hybridomas. The resulting bivariate distribution provides a clear distinction between labelled and unlabelled cell fractions. The method based on nuclei extraction with pepsin digestion was optimized for a hybridoma line used in this study. PMID- 2111761 TI - Simultaneous flow cytometric detection of cellular c-myc protein, incorporated bromodeoxyuridine, and DNA. AB - We describe a multivariate flow cytometric technique for simultaneous analysis of specific nuclear protein, bromodeoxyuridine (BrdUrd) incorporated into DNA and DNA content in single cells in suspension. The procedure involves fixation of BrdUrd-exposed cells with paraformaldehyde, heat denaturation of cellular DNA, followed by sequential immunochemical reactions to label incorporated BrdUrd and nuclear protein, and finally staining of total DNA with propidium iodide. The cells are analyzed flow cytometrically and multivariate data acquired in list mode to facilitate analyses of heterogeneous subpopulations. We applied this technique to measure c-myc protein, incorporated BrdUrd, and DNA content in subpopulations present in a recombinant Chinese hamster ovary (CHO) cell line carrying approximately 800 copies of murine c-myc sequences under control of an inducible heat shock promoter. PMID- 2111762 TI - Effect of portal hypertension on in vivo bile acid-mediated small intestinal mucosal injury in the rat. AB - This study's purpose was to determine whether portal hypertension adversely affects small intestinal mucosal injury. Portal hypertension was produced in male Sprague-Dawley rats by two-stage ligation of the portal vein. Sham-operated rats were used as controls. Two weeks later, intestinal injury was produced by in vivo perfusion with 5 mM chenodeoxycholic acid for 30 min. Intestinal injury was assessed by quantitative morphometry and by measuring intestinal water and mannitol absorption. Portal hypertension resulted in more injury in the distal perfused intestine as manifested by increased villus tip denudation [portal hypertensive 52.5 +/- 9.6 (SEM) vs controls 28.1 +/- 5.7 microns, P = 0.05). Additionally there was a significant decrease in the unperfused duodenal villus height in portal hypertensive rats (portal hypertensive 755 +/- 22 vs controls 848 +/- 28 microns, P less than 0.02). Portal hypertension had no significant effect on the increase in mannitol absorption or water secretion caused by chenodeoxycholic acid perfusion. This study suggests that portal hypertension alters small intestinal mucosa and increases susceptibility to injury. PMID- 2111763 TI - [Determination of soluble tissue-specific antigens of the human skin epithelium in neoplasms of different histogenesis]. AB - Two tissue-specific water-soluble antigens AG1 and AG2 are revealed in immunobiochemical analysis of human squamous epithelium extract. It is established that AG2 with the molecular weight of about 10 kD is of immunodiagnostic significance, being a marker of squamous cell carcinoma of different organs. PMID- 2111764 TI - [Effects of At-211 alpha irradiation on Ehrlich ascites tumor cells]. AB - The biological effect of 211At alpha-particles has been investigated using the Chinese hamster fibroblasts and Ehrlich carcinoma cells growth in vitro. The mean energy of 211At alpha-particles is 6.8 MeV, LET in tissue is 70-160 keV/microns; the half-life period of decomposition of 211At is 7.2 h. The end-points used were a decrease in the mitotic activity, an elevation of the number of degenerating cells, cell with chromosome aberrations and the cell survival. The RBE of alpha particles in comparison with 60Co gamma-rays is close to 3. PMID- 2111765 TI - Modulation of steroid production in goat ovarian cells: effect of progestins and antiprogestins. AB - Effect of various synthetic progestins and antiprogestational compounds on progesterone (P) and estradiol (E) production by isolated goat ovarian granulosa (G) and corpus luteum (CL) cell types was studied in vitro. Steroid production was studied either under basal conditions or after stimulation with follicle stimulating hormone (FSH) in the presence of aromatase substrate, androstenedione (A). None of the progestins had any significant effect on basal P and E production by either cell types during 48 hour of culture. The FSH and A - induced increase in P and E production was significantly inhibited following concommitant treatment with synthetic progestins at concentrations higher than 10(-7) M. The added progestins had no effect on G and CL cell viability. None of the antiprogestational compounds had any significant effect on basal steroid production in either of the cell types. Furthermore, the higher concentrations of three antiprogestins namely RMI 14156, STS 557 and isomer 201 of RMI 12936, were found to stimulate significantly the basal as well as FSH + A - induced production of estradiol in both the cell types. In contrast, the other two antiprogestins tested were found to stimulate the gonadotropin + A - induced production of P. These results indicate that exogeneous progestins directly inhibit the gonadotropin + androstenedione - induced steroid production by G and CL cells in vitro. Moreover, different antiprogestin had different effect on the modulation of steroid production. PMID- 2111766 TI - Clinicoelectrographic concordance between monozygotic twins with severe myoclonic epilepsy in infancy. AB - Clinical features of a pair of monozygotic male twins, both with severe myoclonic epilepsy in infancy (SME), are described. They were almost completely concordant with respect to seizure onset, clinical seizure symptomatology, interictal, and ictal EEG expressions and seizure prognosis. The existence of such twins suggests the possibility that a genetic factor is determinant in the etiology of this particular epileptic syndrome. PMID- 2111767 TI - Clinical and neuropathologic findings in a case of severe myoclonic epilepsy of infancy. AB - The autopsy of a 19-month-old boy with severe myoclonic epilepsy of infancy (SMEI) and sudden unexpected death (SUD) revealed several developmental brain abnormalities. The most striking features were microdysgenesis of cerebellum and cerebral cortex and threefold spinal cord channels with surrounding ectopic tissue. Hippocampus and brainstem were normal. PMID- 2111768 TI - Discontinuation of phenytoin, carbamazepine, and valproate in patients with active epilepsy. AB - The effects of discontinuing individual antiepileptic drugs (AEDs) in patients with active epilepsy who are receiving combination therapy have not been studied systematically. We report a double-blind, prospective study of discontinuation of phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) in 70 patients with chronic active epilepsy. Each drug discontinuation was randomized to one of two relatively fast rates of reduction, and a control group of 25 patients continued with stable therapy. Patients who had CBZ removed had a significant increase in seizures that was maintained for 4 weeks after the end of drug reduction, and 10 of these 23 patients had to restart therapy with CBZ. There was no significant change in seizure numbers in the other groups. Two patients discontinued from VPA had to restart the drug; none had to restart PHT. The optimal rates of reduction of CBZ remain uncertain. There was no evidence for a clinically or temporally distinct burst of "discontinuation seizures" in any group. Any marked increase in seizures always resolved on reintroduction of the discontinued drug. PMID- 2111769 TI - Interaction of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine, with valproate: a pharmacokinetic study. AB - The mechanism responsible for the valproate (VPA)-induced elevation of serum carbamazepine-10,11-epoxide (CBZ-E) levels was investigated in 6 normal subjects who received single oral doses of CBZ-E (100 mg) in a control session and during concurrent treatment with sodium VPA [500 mg twice daily (b.i.d.)]. VPA caused a significant prolongation of CBZ-E terminal half-life (t1/2 from 6.3 +/- 1.2 to 9.0 +/- 2.0 h, mean values +/- SD) and decreased CBZ-E clearance (from 90.6 +/- 18.8 to 63.2 +/- 16.1 ml h-1 kg-1, mean values +/- SD) without affecting CBZ-E apparent volume of distribution (from 0.82 +/- 0.19 to 0.81 +/- 0.24 l kg-1, mean values +/- SD). These findings indicate that VPA impairs the elimination of CBZ E, presumably by inhibiting its metabolism. PMID- 2111770 TI - Possible induction of systemic lupus erythematosus by valproate. AB - Two patients developed clinical and laboratory evidence of systemic lupus erythematosus (SLE) during treatment with valproate (VPA) preparations. The first patient, a 47-year-old man, had fever, malaise, and thrombocytopenia 1 month after VPA was added to phenytoin (PHT) and primidone (PRM). He developed high titers of antinuclear antibodies (ANA) and anti-DNA antibodies, and hypocomplementemia. After discontinuation of PHT and VPA, steroid and immunoglobulin treatment was required for 4 weeks before his condition improved. The second patient, a 28-year-old woman, had been followed for idiopathic leukopenia for 3 years and had previously experienced fever and lymphadenopathy from PHT. After 4 months of divalproex therapy, she developed confusion, joint pain, and a dramatic increase in seizure frequency. She also developed high titers of ANA and anti-DNA antibodies and hypocomplementemia, along with a further decrease in white blood cell (WBC) count. These responded to steroid therapy and withdrawal of divalproex. Three months later, reintroduction of divalproex was followed by a return of ANA in low titer, which resolved after discontinuation. We believe that VPA may have caused true SLE in these patients, one of whom was probably predisposed. PMID- 2111771 TI - Valproate, carnitine metabolism, and biochemical indicators of liver function. Collaborative Group for the Study of Epilepsy. AB - The effects of valproate (VPA) on carnitine and lipid metabolism and on liver function were assessed in 213 age- and sex-matched outpatients from five centers, with the following distribution: VPA monotherapy, 54; VPA polytherapy, 55; other monotherapies, 51; and untreated, 53. Mean total and free carnitine levels were significantly lower in patients with polytherapy; acylcarnitine was significantly higher for VPA monotherapy and the ratio of acyl- to free carnitine was significantly higher in all patients receiving VPA. Ammonia, uric acid, and bilirubin were the only tests selectively impaired with VPA. A significant correlation was found between serum ammonia and VPA dosage. Glucose, beta lipoproteins, triglycerides, acetacetate, and beta-hydroxybutyrate were unchanged in the four groups. Sex and age appeared to interact with total and free carnitine values. Adverse drug reactions were apparently unrelated to carnitine metabolism impairment. Only a few patients had abnormal carnitine values. Our data support the assumption that carnitine deficiency and abnormal liver function due to VPA are mostly subclinical events. PMID- 2111772 TI - Synergistic induction of polypeptides by tumor necrosis factor and interferon gamma in cells sensitive or resistant to tumor necrosis factor: assessment by computer based analysis of two-dimensional gels using the PDQUEST system. AB - Tumor necrosis factor (TNF) synergistically enhanced the antiproliferative activity of interferon-gamma (IFN-gamma) in both TNF-sensitive and TNF-resistant variants of the cervical carcinoma line, ME-180. TNF alone had no apparent effect on the levels of synthesis of individual proteins in either of these variant cell lines as assessed by computerized two-dimensional gel analysis of cell lysates using the PDQUEST system. However, IFN-gamma enhanced the levels of 18 polypeptides and suppressed the levels of 10 polypeptides in both cell lines. When used in combination in both cell lines, TNF and IFN-gamma induced the synthesis of 10 polypeptides that were not induced by either agent alone. These synergistically induced polypeptides may be crucial to the mechanism of the synergistic antiproliferative action of TNF and IFN-gamma in ME-180 cells. PMID- 2111773 TI - Towards establishing a protein database of Drosophila. AB - An improved method of high-resolution two-dimensional gel electrophoresis has been used to study the patterns of protein synthesis in wing imaginal discs of late instar larvae of Drosophila melanogaster. A total of one thousand and twenty five labelled polypeptides (787 acidic and 238 basic) have so far been separated and catalogued. For convenience, all these polypeptides have been numbered and their position fixed by its molecular weight and relative mobility. They are indicated on a reference protein map for further studies. PMID- 2111774 TI - Effects of taprostene, a stable prostacyclin analogue, on haemodynamics, platelet function and arachidonate metabolism in healthy volunteers. AB - In order to assess the effect of taprostene on haemodynamics, platelet function and arachidonate metabolism in 4 healthy volunteers an intravenous infusion of 25 ng.kg-1.min-1 was given for 6 h. During the infusion period systolic blood pressure dropped from 130 to 111 mm Hg and diastolic blood pressure from 77 to 69 mm Hg. The heart rate rose from 77 to 84 beats/min. During the taprostene infusion the slope and height of the ADP and collagen induced platelet aggregation curves were significantly inhibited and the sensitivity of platelets to PGI2 and PGE1 was increased. Plasma and serum thromboxane B2, conversion of exogenous radiolabelled arachidonic acid, WU-test, circulating endothelial cell count, concentration of platelet factor 4, beta-thromboglobulin, malondialdehyde and the PGI2-synthesis stimulating plasma factor did not show any clear drug related alteration. It is concluded that infusion of taprostene 25 ng.kg-1.min-1 caused measurable inhibition of platelet function ex vivo. PMID- 2111775 TI - Gonococcal infection within Scotland: antigenic heterogeneity and antibiotic susceptibility of infecting strains. AB - Two panels of monoclonal antibody reagents were used to serotype all strains of Neisseria gonorrhoeae isolated from four separate geographical areas serving two million of the five million Scottish population. Serotype 1B isolates accounted for 60% of the 869 strains examined and were more prevalent than 1A isolates in each geographical area. A total of 11 1A serovars and 47 1B serovars were recognised. Only two of the 11 1A serovars (Aedgkih/Arost and Aedih/Arst) were found in every centre but these accounted for over 90% of the 1A isolates. Although there was a total of 47 different 1B serovars over 80% of the isolates were accounted for by the ten most commonly encountered serovars. There were, however, marked geographical differences within both major and minor serovars. There was a highly significant difference (P less than 0.001) between protein 1A and 1B serovars with respect to their susceptibility to penicillin. Within each protein 1 type there were also differences in antibiotic susceptibility. Penicillinase-producing N. gonorrhoeae (PPNG) were found in all centres and accounted for 24 (2.8%) of the 869 isolates. The majority of the PPNG (71%) were serotype 1A and with one exception were serovar Aedih/Arst. PPNG strains accounted for 37% (16) of the 43 Aedih/Arst isolates. Epidemiological, diagnostic and therapeutic implications arising from the distinct geographical differences in the pool of circulating gonococci are discussed. PMID- 2111776 TI - Use of DNA fingerprinting in an epidemiologic study of outbreak-specific and non specific strains of group C Neisseria meningitidis. AB - DNA fingerprints of nine group C isolates of Neisseria meningitidis were obtained by digestion with three restriction endonucleases, BamHI, EcoRI, and HindIII. Identical restriction profiles were displayed by five strains isolated from two patients and three contacts during a localized outbreak of meningococcal disease in the area served by our laboratory. A slight difference, appreciable only in the fingerprints obtained with EcoRI, was observed between these isolates and a sixth one isolated from a clinical case occurring in the same area one year later. In contrast, three additional strains, recently isolated from patients in separate areas in Italy, gave restriction profiles differing strikingly from one another and from those produced by the strains isolated in our area. PMID- 2111777 TI - Current status of serotyping of Neisseria gonorrhoeae. AB - Protein I has become the basis of serotyping of N. gonorrhoeae. A panel of 12 anti-protein I monoclonal antibodies is supplied by Syva Company, Palo Alto, CA, through distributors for research purposes only. These distributors are responsible for storing the monoclonal antibodies, supplying research groups and training new users, particularly in the interpretation of coagglutination reactions. A European Workshop was held in Heidelberg, Federal Republic of Germany in July 1988 to discuss serotyping with these antibodies. The current uses of serotyping of N. gonorrhoeae include epidemiological studies, clinical purposes and surveillance of antibiotic resistance and plasmid carriage. Predominant serovars may be subtyped either by additional antibodies or with the use of another technique, such as auxotyping, determination of antibiotic sensitivities, plasmid analysis or genetic fingerprinting. Conversely, there is growing evidence that it may be appropriate to group certain serovars together. Data collected during prevalence studies could be combined with clinical information and an international data bank set up. This supposes a close future collaboration of all groups involved in the epidemiology of N. gonorrhoeae. PMID- 2111778 TI - Detection of a novel "cryptic" plasmid of about 7.8 MDal in a non-penicillinase producing Neisseria gonorrhoeae isolate from Munich. AB - A novel plasmid of about 7.8 megadaltons (MDal) could be detected in a non penicillinase-producing Neisseria gonorrhoeae strain isolated in Munich in 1987. As the strain showed no resistance against commonly used chemotherapeutic agents, at present the plasmid must be described as phenotypically "cryptic". PMID- 2111779 TI - Platelet autoantibodies detected by immunoblotting in systemic lupus erythematosus: association with the lupus anticoagulant, and with history of thrombosis and thrombocytopenia. AB - 71 patients with systemic lupus erythematosus (SLE) were studied for the occurrence of platelet antibodies by immunoblotting. Binding of IgG antibodies to platelet protein antigens was observed in 39 of the 71 patients. The most frequently detected and exceptionally strongly reacting antibodies were directed against platelet protein antigens with an approximate molecular weight of 65 kDa under nonreducing conditions. These antibodies were autoreactive and, when followed, they usually persisted. Interestingly, in this group of well-defined SLE patients, platelet antibodies against the most common targets (65 kDa) were significantly associated with the lupus anticoagulant, a history of thrombocytopenia and thrombosis, particularly with arterial occlusions. The lupus anticoagulant, on the other hand, correlated significantly only with venous thrombosis. In addition to the lupus anticoagulant, platelet antibodies against this unknown platelet protein may thus be a marker of a higher risk of thrombosis in SLE patients. PMID- 2111781 TI - [Acute icteric viral hepatitis type A, B, D and non-A non-B. Etiologic, clinical and developmental aspects in the young man. Apropos of 423 cases]. AB - In the light of the present serological tests, the etiology, clinical features and course of acute viral hepatitis were reviewed in 423 consecutive male patients. Follow-up started less than 15 days after the onset of jaundice and continued until recovery or for at least six months if recovery did not occur before them. The incidence of type A viral hepatitis decreased in France but remained high in North Africa and tropical areas. During the acute phase it differed from hepatitis type B by a lower aminotransferase level. Relapse, however, was more common, as was protraction of longer than six months. Recovery ultimately occurred. The specific IgM antibody persisted throughout the condition. Type B hepatitis differed from type A hepatitis by a mean quicker normalization of the biochemical disturbances. In the absence of superinfection by delta hepatitis virus or by a non-A, non-B virus, the progression to chronic liver disease was rare. The course of non-A, non-B hepatitis was very dissimilar according to the circumstances of occurrence. In epidemic cases rapid recovery occurred and no progression to chronicity was noted. In the other cases, relapse and chronicity were more frequent than for type A or B hepatitis. Type D hepatitis was characterized by more pronounced biochemical disturbances during the acute phase and by more frequent progression to chronicity in case of superinfection. PMID- 2111780 TI - Immunoregulatory effect of a synthetic peptide corresponding to a region of protein p24 of HIV. AB - The effect of a synthetic peptide, corresponding to a sequence of HIV-1 p24 protein (amino acids 218-237), on in vitro immune responses was studied. The peptide inhibited in a dose-dependent manner the induction of an anti-SRC antibody response and of a PPD-specific proliferative response of human PBL. On the other hand, PHA-induced proliferation of human PBL and PPD-induced proliferation of a PPD-specific human T-cell line were not modified by comparable amounts of the peptide. These results suggest that structures from a protein (p24), present in the serum throughout the course of HIV infection, are able to interfere with the inductive stages of specific immune responses. These findings may help to unravel some of the pathogenic mechanisms of AIDS and may contribute to the development of vaccine strategies. PMID- 2111782 TI - Acid-base regulation of ion transport in rabbit ileum in vitro. AB - Changes in acid-base balance have a major influence on ion transport in the ileum. The goals of the present study were to delineate (a) the specific transport processes most affected by changes in acid-base metabolism, (b) the individual roles of pH, PCO2, and concentration of HCO3- in modulating ion transport, and (c) the relationship between acid-base sensitive and other ion transport systems. Ion transport and electrical parameters were measured in rabbit ilea in vitro under short-circuit conditions with systematic variations of pH, PCO2, and concentrations of HCO3-. Increasing HCO3- concentrations, with constant PCO2 and increasing pH, caused a decrease in electroneutral Na+ and Cl- absorption. At 5 mmol/L HCO3-, net fluxes of Na+ and Cl- were 5.9 +/- 1.4 and 4.5 +/- 1.1 microEq.cm-2.h-1, while at 50 mmol/L HCO3-, net Na+ and Cl- fluxes were 0.7 +/- 0.7 and 0.2 +/- 0.6 microEq.cm-2.h-1. Transepithelial HCO3(-)-gradient experiments suggested that serosal HCO3- was the principal factor. Changes in PCO2 showed a complex biphasic response, increasing net Cl- flux as PCO2 increased from 11-30 mm Hg in 5 mmol/L HCO3-; net Na+ flux increased as PCO2 was changed from 36 to greater than 100 mm Hg in 22 mmol/L HCO3-. In contrast, increasing pH in a bicarbonate-free N-2-hydroxyethylpiperazine-N'-2 = ethane sulfonic acid buffer did not significantly alter Na+ transport. Acid-base stimulated Na+ absorption was inhibited by 10(-3) mol/L amiloride, but not by bumetanide, consistent with the involvement of Na(+)-H+ exchange rather than Na(+)-Cl- cotransport. Epinephrine did not increase Na+ absorption under acid base stimulated conditions, but glucose did, suggesting that the rate-limiting step for electroneutral absorptive processes under these conditions occurs at the apical rather than the basolateral membrane. Combining all experiments, a significant correlation existed between net flux of Na+ and HCO3- concentration (r = -0.72, P less than 0.05) and between net flux of Na+ and pH (r = -0.68, P less than 0.01). Chloride absorption was correlated with pH (r = 0.72, P less than 0.01). These results suggest a profound regulatory role for acid-base balance in electroneutral Na(+)-Cl- transport in rabbit ileum in vitro. PMID- 2111783 TI - Gastric lipase in alcoholic pancreatitis. Comparison of secretive profiles following pentagastrin stimulation in normal adults and patients with pancreatic insufficiency. AB - The aims of this study were to evaluate the amount of gastric lipase secreted by the stomach in normal adults and to elucidate a possible adaptative secretion of this enzyme in response to pancreatic insufficiency secondary to alcoholic chronic pancreatitis. Forty-one subjects underwent a gastric intubation. Pentagastrin (6 micrograms.kg-1.h-1 IV) significantly increased gastric lipase concentration and output. Stimulated gastric lipase output in seven normal subjects was 12,598 +/- 2036 U/h (by using tributyrin as substrate). Outputs where higher (P less than 0.02) in 17 patients with pancreatic insufficiency who were not drinking alcohol, but were not significantly different in nine patients who continued to drink (20,413 +/- 1778 U/h and 21,953 +/- 4973 U/h, respectively). On the other hand, high gastric lipase outputs were found in eight patients with duodenal ulcers and no evidence of pancreatic dysfunction (23,180 +/- 262 U/h). The time required to reach maximal lipase output (peak output) following pentagastrin stimulation was the same in all groups (approximately 38 minutes) except for the group of patients with pancreatic insufficiency who did not drink alcohol, in whom it was significantly reduced (approximately 26.5 minutes). Secretory patterns of gastric lipase and pepsin were closely comparable. Gastric lipase secretion could be increased in several clinical conditions and particularly in patients with pancreatic insufficiency caused by alcoholic chronic pancreatitis who have been abstinent for a long time. PMID- 2111784 TI - Cost-effectiveness of cimetidine maintenance therapy in chronic gastric and duodenal ulcer. AB - The effects of cimetidine maintenance therapy on the socioeconomic life of patients with peptic ulcers in the 3 years after healing and the extent to which treatment was cost-effective were studied. Three hundred eleven patients with healed ulcers (184 gastric, 127 duodenal) were studied for periods of up to 3 years; 261 patients (152 gastric ulcer, 109 duodenal ulcer) completed the 3-year follow-up. Cimetidine (400 mg at night) was compared with placebo in a double blind, randomized prospective study. Intention-to-treat analysis was used. In the placebo group, the major costs of ulcer disease in gastric ulcer patients were attributable to endoscopic procedures and absenteeism; in duodenal ulcer patients, the major costs were endoscopic procedures, absenteeism, and surgery. Cimetidine was cost-effective in both gastric ulcer and duodenal ulcer patients in the first 2 years after healing. Over the 3-year period it was also cost effective, but no benefit was seen in the third year. PMID- 2111785 TI - Glutamine: an essential nonessential amino acid for the gut. PMID- 2111788 TI - [Dynamics of heat shock puffs in highly-inbred strains and heterosis hybrids of Drosophila melanogaster]. AB - This study is aimed at elucidating the mechanisms of high heat resistance of heterosis hybrids. For this purpose, the dynamics of heat shock puffs of the high inbred HA and BA lines as well as the HAxBA heterosis hybrids has been studied. Inadaptive properties of the HA line were observed to be expressed at the organism and cell levels, which is reflected by later induction of heat shock puffs. In the hybrids, these puffs occur considerably quicker, when heated, than with the high-inbred lines. Our conclusion is that the dynamics peculiarities of heat shock puffs reflect the differences in line and hybrid heat resistance. The higher heat resistance of the hybrid manifests itself in an earlier induction of heat shock puffs. PMID- 2111786 TI - Human antral damage induced by alcohol is potentiated by enprostil. AB - Enprostil, a synthetic analogue of prostaglandin E2, has been shown to protect the human gastroduodenal mucosa from aspirin injury. This study was designed to determine if enprostil protected against alcohol damage. A double-blind, randomized, cross-over study was performed on eight healthy adult men. After an overnight fast, a gastroscope was inserted and the antral mucosa was sprayed with a 10-mL test solution containing either enprostil (70 micrograms) or its vehicle (control). After 15 minutes, mucosal injury was scored (0-5), and the mucosa was sprayed with 100 mL 80% ethanol. Mucosal injury was scored after a further 15, 20, 25, and 30 minutes. The entire experiment was recorded on video film, which a second endoscopist used to score the damage independently. The two experiments were separated by an interval of 1 week. There was close agreement between the two endoscopists (r = 0.9385), and their scores were averaged. Using Friedman's two-way analysis of variance, a highly significant (P less than 0.00004) increase in injury was demonstrated following enprostil pretreatment. The Wilcoxin signed rank test showed the differences to be significant (P less than 0.05) at every time point. We conclude that enprostil, rather than protecting the human antral mucosa from alcohol injury, appears to potentiate this injury and may itself be damaging in therapeutic concentrations. This unexpected result cannot yet be explained but demands caution in the clinical use of enprostil. PMID- 2111787 TI - [Mapping of the gene coding for the major protein of the ejaculatory bulb in Drosophila melanogaster]. AB - The major protein of ejaculatory bulb of Drosophila melanogaster males (PEB-me) is represented by a group of 4-5 sufbractions. Four PEB variants differing in SDS PAGE mobility were found. The results of genetic analysis suggest that electrophoretic mobility of the entire complex of protein PEB bands is controlled by a single locus (peb). The locus is therefore supposed to contain the structural gene for the subfractions of PEB. Its genetic and cytological location is 2-107.2-2-108.0 and 60E11-60F5, respectively. PMID- 2111789 TI - [Mating behavior in Drosophila melanogaster males heterozygous for the dominant temperature-sensitive lethal mutation]. AB - The influence of two mutations on the mate success of Drosophila melanogaster males was studied. Dominant temperature-sensitive lethal mutations l(2)M167DTS and l(2)M65DTS were used in experiments. Both these mutations are recessive lethals in homozygote. Individuals l(2)M65DTS and l(2)M167DTS die at 17 and 28 degrees C, respectively. The mate success of l(2)M65DTS males is much lower than that of normal males. In the experiments conducted in autumn, l(2)M167DTS males were always at advantage, whatever their age. In the winter experiments, they were only at advantage at the age of 2-3 and 15-17 days. For l(2)M167DTS males, a relationship has been established between the mate success and t degrees, and season. The role of behavioural pleiotropic effects of mutations on the probability of their fixation in a population is discussed. PMID- 2111790 TI - [The effect of sterol metabolism in a model ecological system Drosophila-yeasts on the crossing-over in Drosophila]. AB - The absence of sterols available for metabolism causes the death of Drosophila larva. Addition of suboptimal cholesterol doses to this medium allows the portion of larvae to survive. Sterol-deficient diet at the preimaginal stages leads to suppression of both spontaneous and high-temperature induced crossingover in Drosophila females. Two possible explanations for dependence of recombination process on sterol metabolism are suggested: 1) the shortage of precursor for ecdisons biosynthesis was the cause of discordance of meiotic events; 2) suppression of crossingover occurs, due to alteration of cell membrans' structure. PMID- 2111791 TI - [Mutational variability of enzyme loci in unstable Drosophila melanogaster strains]. AB - Biochemical analysis of a number of related unstable Drosophila melanogaster strains was carried out. These strains have been shown to undergo mutational transformations caused by insertion/excision of transposable elements (Gerasimova, 1985). Activity and mobility variants of alpha-GPDH, ADH, SOD, G6PD, 6PGD and EST-6 were analysed. Two loci controlling SOD and 6PGD proved to be invariable, the loci alpha-Gpdh and Est-6 causing reduced activity of their products in the initial strain ctMR2. The direct and reversed transformations analogous to the mutational passages of morphological characters were traced in two loci controlling ADH and G6PD. The data obtained are discussed in terms of up to-date views on the functional role of transposable elements, in relation to the genetic stability of the strains studied, under the multiple transpositions of mobile elements. PMID- 2111792 TI - [The effect of ts-mutation on expression of genes induced by heat shock in Drosophila melanogaster. III. Synthesis of proteins cognate to HSP70]. AB - 2D-electrophoresis performed as described by O'-Farrel has revealed clear-cut differences in the pattern of proteins synthesized in the cells of wild-type flies and in the cells of ts-lethal. The cells of the mutant studied after heat shock exhibit not only the lack of HSP83 and HSP35 but also the absence of a few of the heat-shock proteins belonging to the HSP70 group. Moreover, in the cells of the mutant an intensive synthesis of a protein with mol. weight 72 KDa was observed after heat-shock. This protein belongs to highly abundant heat-shock cognate proteins (HSCP) which are usually not induced by temperature elevation. PMID- 2111793 TI - Effects of TCDD on vitamin A status and liver microsomal enzyme activities in a TCDD-susceptible and a TCDD-resistant rat strain. AB - To investigate the relationship between vitamin A status and 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) lethality, the influence of TCDD on tissue and serum vitamin A levels was determined in the most TCDD-susceptible (Long-Evans) and the most TCDD-resistant (Han/Wistar) rat strains. The TCDD LD50 values of these two strains differ by a factor of more than 300. Groups of three rats per strain were used in a dose-response study (given single ip doses of 0, 4, 40, 400, 800 or 1600 micrograms TCDD/kg body weight and killed on day 11) and in a time-course experiment (given single ip doses of 0, 4 and, in the case of Han/Wistar rats only, 1600 micrograms TCDD/kg body weight, and killed on days 4, 11, 23, 50 and 76). The strains showed similar response over the 76-day study with respect to vitamin A levels in the liver, kidneys, testicles and serum after exposure to a sublethal dose of TCDD (4 micrograms/kg body weight). In contrast, TCDD doses lethal to the Long-Evans strain only (40-1600 micrograms/kg, day 11) markedly increased kidney and serum vitamin A levels in Han/Wistar rats, while they were practically without effect in Long-Evans rats. Hepatic cytochrome P-450 concentration, and the activities of 7-ethoxyresorufin O-deethylase, ethylmorphine N-demethylase, and uridine diphosphate glucuronosyltransferase (towards p-nitrophenol) were affected by the TCDD doses in much the same manner in both strains. These findings show that the correlations between TCDD lethality and changes in vitamin A status found among species of laboratory animals do not hold for Long-Evans and Han/Wistar strains of rat. PMID- 2111794 TI - Asialoagalacto-choriongonadotropin, an antagonist of the action of Graves' immunoglobulins in human thyroid membranes with a limited affinity for hepatic receptors. PMID- 2111795 TI - Passive transport of thyroid hormones from extravascular space into the circulation. PMID- 2111796 TI - Protection of mice against Brucella abortus by immunization with polyclonal anti idiotype antibodies. AB - Polyclonal goat anti-idiotypic antibodies containing internal images which mimic Brucella abortus antigens were generated from rabbit polyclonal idiotypes specific for partially purified extract of B. abortus (PX III). The anti idiotypic antibodies were purified using two-step immunoaffinity column chromatography. The presence of internal images was demonstrated by competitive inhibition analysis using an enzyme-linked immunosorbent assay. Several groups of BALB/c mice were vaccinated with the anti-idiotypic antibodies. The vaccinated mice showed a high serum titer of antibodies specific for B. abortus. When the vaccinated mice were challenged with a virulent B. abortus strain 2308, greater than 90% reduction of bacteria in the spleen as compared to the unvaccinated control groups was seen. Immunoblotting experiments using antiserum from vaccinated mice demonstrate the ability to distinguish vaccinated mice from B. abortus infected mice. Our data indicate that the anti-idiotypic antibody containing internal images of B. abortus may be used as a vaccine and the induced antibody can be distinguished by immunoblotting from antibodies generated by natural infection with B. abortus. PMID- 2111797 TI - Influence of local radiotherapy of breast cancer patients on the frequency of cytotoxic T lymphocyte precursor cells. AB - Alloantigen-specific cytotoxic T lymphocyte precursor (CTL-p) frequencies were analyzed in ten patients with histologically proven breast cancer receiving prophylactic RT. The frequency of CTL-p was assessed by limiting dilution (LD) analyses before, immediately after discontinuation of treatment and at various times following RT. The number of pbmnc, adherent cells and T cells was determined in parallel. Local RT led to a minor and transient reduction of CTL-p frequencies lasting approximately three months: on average a 25% decrease of CTL p numbers was seen immediately after RT. Three months following treatment, a 20% reduction was still evident. Values subsequently returned to pretreatment levels. Moreover, these changes in the frequency of antigen-specific CTL were accompanied by a 25% to 39% decrease in the blood T cell counts lasting for more than 12 months. The reductions following local RT were less pronounced than those induced by immunosuppressive drugs in allograft recipients. PMID- 2111798 TI - Nomenclature for factors of the HLA system, 1989. PMID- 2111799 TI - Isolation rates of different mycobacterial species from Chandigarh (north India). AB - A total of 4958 patients, clinically suspected to have tuberculosis were screened for mycobacteria by acid fast staining and culture procedures. Mycobacterial species were isolated from 462 (9.3%) patients while acid fast bacilli were demonstrated on smear examination in 83 (1.7%) patients. Mycobacterium tuberculosis was the most common isolate (92%). Among the nontuberculous mycobacteria, M. fortuitum was isolated in 13 (2.8%), M. avium in 2 (0.4%) and M. szulgai in 1 (0.2%). In 22 individuals clinically suspected of tubercular pleural effusion, pleural biopsy specimen gave higher isolation of mycobacteria (27.3%) as compared to isolations from pleural fluid specimens (9.1%). PMID- 2111800 TI - Clinical, histopathologic & immunologic features of cutaneous lesions in acute meningococcaemia. AB - Fifty children with culture proven acute meningococcaemia were studied during the winter outbreak of the disease in 1986-87. Purpuric lesions were seen in 60 per cent, erythematous papules in 32 per cent, faint pink macules in 28 per cent, conjunctival petechiae in 10 per cent and herpes labialis in 20 per cent. Histopathology of skin lesions showed that the primary damage was to the dermal vessels, the extent of damage depending on the type of skin involvement. Diplococci in Gram's stained sections were seen frequently in purpuric as compared to the other skin lesions. They were located in degenerating neutrophils, endothelial cells, fibrin clots or freely in the vascular lumen. Electron microscopic study showed vascular changes accompanied by a perivascular phagocytic response. Both light and electronmicroscopy indicated the involvement of the coagulative mechanism in the pathogenesis of meningococcaemia. However, clinical parameters of clotting were often within normal limits. In the case of a child (who died eventually), a low platelet count and prolonged coagulation indices were observed. Sera from some of the children were tested for the presence of antibodies against meningococci by indirect immunofluorescence. Antibodies were detected in the sera and they may have a role in regulating the severity and course of the illness. The significance of immunoglobulin deposits in the skin lesions is not clear. PMID- 2111801 TI - Survey of ticks (Acarina: Ixodidae) for Crimean haemorrhagic fever virus activity in Jammu & Kashmir state, India. AB - A survey of ixodid ticks was carried on in 1977 to determine the crimean haemorrhagic fever (CHF) virus activity in Jammu & Kashmir state, India. In all, 412 immatures and 3258 adults belonging to 7 genera and 16 species of ticks were collected as ectoparasites of small and large mammals. These included one species each of the genera Boophilus, Dermacentor and Nosomma, 2 species of Rhipicephalus, 3 species of Ixodes and 4 species each of Haemaphysalis and Hyalomma. Haem. bispinosa was the predominant species followed by B. microplus, Haem. montgomeryi, R. haemaphysaloides and Hyal. m. isaaci. The four Hyalomma species viz., Hyal. a. anatolicum (incriminated as the vector of CHF virus), Hyal. detritum, Hyal. dromedarii and Hyal. m. isaaci were found parasitizing goat, sheep, camel and cattle and were collected in the districts of Jammu, Rajouri, Poonch and Udhampur. Four species viz., Haem. intermedia, Hyal. detritum, Hyal. dromedarii and Hyal. m. isaaci are new records for the state. A total of 138 pools comprising eight species under six genera of ticks were processed for isolating the virus. CHF virus was not isolated. The role of ixodid ticks, particularly those of the genus Hyalomma in the dissemination of CHF virus is highlighted. PMID- 2111802 TI - [Phenothiazine-induced pseudolymphoma]. AB - A 59-year-old male patient developed lymphoma-like cutaneous infiltrates on the back and left side following treatment with levomepromazine (Neurocil) over many years. Complete remission after discontinuation of levomepromazine and its replacement by a drug of another chemical class (melperone, Eunerpan) confirmed the causative role of the phenothiazine in the development of pseudolymphoma. PMID- 2111803 TI - Two different secretion mechanisms in the inner ear's interdental cells. AB - Fixation with a mixture of tannic acid and glutaraldehyde reveals a darkly stained substance in the intercellular clefts between juxtapposed interdental cells, where it is included by pynocytotic vesicles. Over the interdental cells, similar-sized vesicles (35-45 nm) are present in clear spaces of the amorphous layer of the limbal portion of the tectorial membrane. Some images suggest that they may be secreted through small disruptions of the membrane of the interdental cells' microvilli. In addition, a TA-unstained, amorphous material is present inside both basal ducts and apical cavities of the interdental cells, thus suggesting another secretory route from the basal region of the interdental cells towards either the endolymph, or the tectorial membrane. These two secretion processes coexist in a single interdental complex, and the two secretion products may be involved in the turnover of the adult tectorial membrane and/or the secretion of some component of the endolymph. PMID- 2111804 TI - The A-factor-binding protein of Streptomyces griseus negatively controls streptomycin production and sporulation. AB - A-factor, 2-(6'-methylheptanoyl)-3R-hydroxymethyl-4-butanolide, is an autoregulator essential for streptomycin production and sporulation in Streptomyces griseus. S. griseus 2247 that requires no A-factor for streptomycin production or sporulation was found to have a defect in the A-factor-binding protein. This observation implied that the A-factor-binding protein in the absence of A-factor repressed the expression of both phenotypes in the wild-type strain. Screening among mutagenized S. griseus colonies for strains producing streptomycin and sporulating in the absence of A-factor yielded three mutants that were also deficient in the A-factor-binding protein. Reversal of the defect in the A-factor-binding protein of these mutants led to the simultaneous loss of streptomycin production and sporulation. These data suggested that the A-factor binding protein played a role in repressing both streptomycin production and sporulation and that the binding of A-factor to the protein released its repression. Mutants deficient in the A-factor-binding protein began to produce streptomycin and sporulate at an earlier stage of growth than did the wild-type strain. These mutants produced approximately 10 times more streptomycin than did the parental strain. These findings are consistent with the idea that the intracellular concentration of A-factor determines the timing of derepression of the gene(s) whose expression is repressed by the A-factor-binding protein. PMID- 2111805 TI - Identification and characterization of hetA, a gene that acts early in the process of morphological differentiation of heterocysts. AB - Envelope polysaccharide is a major early diagnostic of differentiating heterocysts. The mutation in mutant EF116 of Anabaena sp. strain PCC 7120 reduces the cohesiveness of this polysaccharide. A 3.5-kilobase fragment of DNA cloned from the wild type of this Anabaena sp. was previously shown to complement this mutation. We present the nucleotide sequence of a 2,555-base-pair portion of this fragment containing an open reading frame (ORF) of 601 amino acids. Complementation analysis using deletion derivatives of the 3.5-kilobase fragment showed that the gene mutated in EF116, which we designate hetA, lies within this ORF. Transcription of hetA was induced as a result of deprivation for nitrate and yielded a monocistronic mRNA that was present at greatest abundance 7 h after nitrogen stepdown. At that time, proheterocysts could not be distinguished by light microscopy; transcription of nifHD, structural genes of nitrogenase, peaked much later. Situated 3' to hetA are 4 identical repeats of the sequence 5' TTCAAAA-3' and 12 repeats (10 identical) of the sequence 5'-CCCCAAT-3'. The 12 repeats, present within and near the 5' end of a second ORF, are almost identical to repeats that have been reported to be present in the region between the petC and petA genes of a related cyanobacterium. PMID- 2111806 TI - Overproduction, purification, and characterization of Bacillus subtilis RNA polymerase sigma A factor. AB - By use of a T7 expression system, large amounts of active Bacillus subtilis RNA polymerase sigma A factor were produced in Escherichia coli cells. This overproduced protein was found in the form of inclusion bodies and constituted 40% of the total cellular protein. Because of the ease of isolation of the inclusion bodies and the acidic properties of sigma A, the protein was purified to more than 99% purity and the yield was about 90 mg/liter of culture. Gel mobility, antigenicity, specificity of promoter recognition, and N-terminal amino acid sequence of the overproduced sigma were found to be the same as those of native sigma A. Partial proteolysis analysis of sigma A protein suggested the presence of a protease-sensitive surface region in the C-terminal part of the sigma A protein. The promoter -10 binding region of sigma A was less sensitive to proteases and was probably involved in a hydrophobic, tightly folded domain of sigma A protein. PMID- 2111807 TI - The Rhizobium meliloti trpE(G) gene is regulated by attenuation, and its product, anthranilate synthase, is regulated by feedback inhibition. AB - In Rhizobium meliloti, the genes involved in biosynthesis of the amino acid tryptophan are found at three separate chromosomal locations. Of the three gene clusters, trpE(G), trpDC, and trpFBA, only the trpE(G) gene is regulated by the end product of the pathway, tryptophan. We found that trpE(G) mRNA contains a leader transcript that terminates at a stem-loop structure in a putative transcription attenuator. The level of this leader transcript was constant regardless of the amount of tryptophan in the growth medium. However, the level of full-length trpE(G) mRNA decreased as the amount of tryptophan increased. The beta-galactosidase activity of an R. meliloti strain carrying a trpL'-'lacZ fusion remained constant at different tryptophan concentrations, but the beta galactosidase activity of the same strain carrying a trpE(G)'-'lacZ fusion decreased as the tryptophan concentration increased. These data indicate that transcription of the R. meliloti trpE(G) gene is regulated only by attenuation. We also found that the product of the trpE(G) gene, anthranilate synthase, is feedback inhibited by tryptophan. PMID- 2111808 TI - Studies of sigma D-dependent functions in Bacillus subtilis. AB - Gene expression in Bacillus subtilis can be controlled by alternative forms of RNA polymerase programmed by distinct sigma factors. One such factor, sigma D (sigma 28), is expressed during vegetative growth and has been implicated in the transcription of a regulon of genes expressed during exponential growth and the early stationary phase. We have studied several functions related to flagellar synthesis and chemotaxis in B. subtilis strains in which sigma D is missing or is present at reduced levels. Previous studies showed that a null mutant, which contains a disrupted copy of the sigma D structural gene (sigD), fails to synthesize flagellin and grows as long filaments. We now show that these defects are accompanied by the lack of synthesis of the methyl-accepting chemotaxis proteins and a substantial decrease in two autolysin activities implicated in cell separation. A strain containing an insertion upstream of the sigD gene that reduces the level of sigma D protein grew as short chains and was flagellated but was impaired in chemotaxis and/or motility. This reduced level of sigma D expression suggests that the sigD gene may be part of an operon. A strain containing an insertion downstream of the sigD gene expressed nearly wild-type levels of sigma D protein but was also impaired in chemotaxis and/or motility, suggesting that genes downstream of sigD may also be involved in these functions. Genetic experiments demonstrate that sigD is allelic to the flaB locus, which was initially isolated as a locus affecting flagellin expression (G. F. Grant and M. I. Simon, J. Bacteriol. 99:116-124, 1969). PMID- 2111809 TI - High-frequency, site-specific recombination between lactococcal and pAM beta 1 plasmid DNAs. AB - In vivo recombination events involving the 75-kilobase lactose proteinase plasmid pCI301 of Lactococcus lactis subsp. lactis UC317 and the conjugative enterococcal plasmid pAM beta 1 were analyzed. A fragment, identified as containing the pCI301 recombination site, mediated greatly elevated levels of mobilization and recombination with pAM beta 1 when cloned in a nonmobilizable L. lactis Escherichia coli shuttle vector. This latter recombination event was site and orientation specific on both plasmids. Recombination on pAM beta 1 was within the region associated with plasmid replication, but no effect on pAM beta 1 replication functions was detected. Resolution of recombinant plasmids generated derivatives indistinguishable from the parental plasmids. PMID- 2111810 TI - Construction of broad-host-range plasmid vectors for easy visible selection and analysis of promoters. AB - We have constructed a series of broad-host-range plasmids which use "visual screens" to detect promoter activity. These plasmids contain the pMB1 and pRO1600 origins of replication and are capable of replicating in a wide range of gram negative bacteria. The genes encoding beta-galactosidase and alkaline phosphatase from Escherichia coli and bacterial luciferase from Vibrio harveyi supply the promoterless indicator genes. The constructs were tested in E. coli and Pseudomonas aeruginosa. PMID- 2111811 TI - Characterization of an inducible oxidative stress system in Bacillus subtilis. AB - Exponentially growing cells of Bacillus subtilis demonstrated inducible protection against killing by hydrogen peroxide when prechallenged with a nonlethal dose of this oxidative agent. Cells deficient in a functional recE+ gene product were as much as 100 times more sensitive to the H2O2 but still exhibited an inducible protective response. Exposure to hydrogen peroxide also induced the recE(+)-dependent DNA damage-inducible (din) genes, the resident prophage, and the product of the recE+ gene itself. Thus hydrogen peroxide is capable of inducing the SOS-like or SOB system of B. subtilis. However, the induction of this DNA repair system by other DNA-damaging agents is not sufficient to activate the protective response to hydrogen peroxide. Therefore, at least one more regulatory network (besides the SOB system) that responds to oxidative stress must exist. Furthermore, the data presented indicate that a functional catalase gene is necessary for this protective response. PMID- 2111812 TI - Transduction of a plasmid containing the bacteriophage D3 cos site in Pseudomonas aeruginosa. AB - Plasmids harboring the cos sequences of bacteriophage D3 can be transferred, by bacteriophage D3, into Pseudomonas aeruginosa by a mechanism which is insensitive to DNase. Transducing activity was separated from the plaque-forming particles by CsCl equilibrium gradient centrifugation. Restriction endonuclease digestion patterns suggest that the transducing particles contain plasmid concatemers. PMID- 2111813 TI - The protease inhibitory properties of the Alzheimer's beta-amyloid precursor protein. AB - We have expressed the 57-amino acid Kunitz domain of the Alzheimer's beta-amyloid precursor protein (APP751) as a bacterial fusion protein. The protease inhibitory properties of the purified fusion protein, BX9, were virtually identical in all respects tested to those of purified secreted APP751. Both proteins strongly inhibited pancreatic trypsin (Kis = 0.2 and 0.3 nM) and less well epidermal growth factor-binding protein (Kis = 1 and 3.5 nM), alpha-chymotrypsin (Kis = 3 and 6 nM), and the gamma-subunit of nerve growth factor (Kis = 8 and 9 M). Neither protein appreciably inhibited plasma and pancreatic kallikreins, thrombin, lung tryptase, neutrophil elastase, or cathepsin G. The remarkable similarity of the protease inhibitory profile of BX9 to that of secreted APP751 suggests that proper intramolecular disulfide bond formation has occurred in the bacterial fusion protein and leads to the conclusion that the amyloid precursor protein Kunitz domain is a relatively specific inhibitor of only a few trypsin like arginine esterases. PMID- 2111814 TI - Cloning of a cDNA encoding adenylosuccinate lyase by functional complementation in Escherichia coli. AB - Adenylosuccinate lyase was cloned by functional complementation of an Escherichia coli purB mutant using an avian liver cDNA expression library. The derived amino acid sequence is homologous to the bacterial purB-encoded adenylosuccinate lyase which catalyzes the same two steps in purine biosynthesis as the enzyme from animals. Avian adenylosuccinate lyase also shows regions of extensive sequence similarity to the urea cycle enzyme, argininosuccinate lyase. This homology suggests a similar mechanism for catalysis. Homology of adenylosuccinate and argininosuccinate lyases is intriguing because chickens do not utilize the urea cycle in nitrogen excretion. This is the first report of the cloning of a eukaryotic cDNA encoding adenylosuccinate lyase, and it affords a route to isolate the corresponding human gene which has been suggested to be defective in autistic children. PMID- 2111815 TI - Binding of ATP to eukaryotic initiation factor 2. Differential modulation of mRNA binding activity and GTP-dependent binding of methionyl-tRNAMetf. AB - Eukaryotic initiation factor 2 (eIF-2) is shown to bind ATP with high affinity. Binding of ATP to eIF-2 induces loss of the ability to form a ternary complex with Met-tRNAf and GTP, while still allowing, and even stimulating, the binding of mRNA. Ternary complex formation between eIF-2, GTP, and Met-tRNAf is inhibited effectively by ATP, but not by CTP or UTP. Hydrolysis of ATP is not required for inhibition, for adenyl-5'-yl imidodiphosphate (AMP-PNP), a nonhydrolyzable analogue of ATP, is as active an inhibitor; adenosine 5'-O-(thiotriphosphate) (ATP gamma S) inhibits far more weakly. Ternary complex formation is inhibited effectively by ATP, dATP, or ADP, but not by AMP and adenosine. Hence, the gamma phosphate of ATP and its 3'-OH group are not required for inhibition, but the beta-phosphate is indispensible. Specific complex formation between ATP and eIF-2 is shown 1) by effective retention of Met-tRNAf- and mRNA-binding activities on ATP-agarose and by the ability of free ATP, but not GTP, CTP, or UTP, to effect elution of eIF-2 from this substrate; 2) by eIF-2-dependent retention of [alpha 32P]ATP or dATP on nitrocellulose filters and its inhibition by excess ATP, but not by GTP, CTP, or UTP. Upon elution from ATP-agarose by high salt concentrations, eIF-2 recovers its ability to form a ternary complex with Met tRNAf and GTP. ATP-induced inhibition of ternary complex formation is relieved by excess Met-tRNAf, but not by excess GTP or guanyl-5'-yl imidodiphosphate (GMP PNP). Thus, ATP does not act by inhibiting binding of GTP to eIF-2. Instead, ATP causes Met-tRNAf in ternary complex to dissociate from eIF-2. Conversely, affinity of eIF-2 for ATP is high in the absence of GTP and Met-tRNAf (Kd less than or equal to 10(-12) M), but decreases greatly in conditions of ternary complex formation. These results support the concept that eIF-2 assumes distinct conformations for ternary complex formation and for binding of mRNA, and that these are affected differently by ATP. Interaction of ATP with an eIF-2 molecule in ternary complex with Met-tRNAf and GTP promotes displacement of Met-tRNAf from eIF-2, inducing a state favorable for binding of mRNA. ATP may thus regulate the dual binding activities of eIF-2 during initiation of translation. PMID- 2111816 TI - Evidence for the presence of a phosphatidylinositol anchor on the lipoarabinomannan and lipomannan of Mycobacterium tuberculosis. AB - The recent availability (Hunter, S.W., Gaylord, H., and Brennan, P.J. (1986) J. Biol. Chem. 261, 12345-12351) of the well known arabinomannan of Mycobacterium leprae and Mycobacterium tuberculosis as the pure native lipoarabinomannan has resulted in its implication in key aspects of the immunopathogenesis of leprosy and tuberculosis. We had indicated that the lipid moiety of lipoarabinomannan is probably based on a diacylglycerol unit in that glycerol and the two fatty acids, hexadecanoate and 10-methyloctadecanoate, were identified. In addition, lipoarabinomannan was also shown to contain myo-inositol 1-phosphate. Evidence is now presented, based on selective radiolabeling and analysis of various cleavage fragments, that the inositol phosphate exists as both an alkalilable phosphodiester and as part of a phosphatidylinositol "membrane anchor." The mannan of M. tuberculosis was also isolated as the native lipomannan. It also apparently contains a phosphatidylinositol unit but is devoid of the alkali labile inositol phosphate residues. These lipopolysaccharides are apparently multiglycosylated versions of the well known myocobacterial mannosyl phosphatidylinositols and are prokaryotic versions of the growing list of phosphatidylinositol-anchored macromolecules. Immunogold labeling demonstrates that lipoarabinomannan is a true antigenic capsular or extracellular product of M. tuberculosis. The presence of a phosphatidylinositol residue on lipoarabinomannan may explain its interaction with macrophage membranes and role in mycobacterial pathogenesis. PMID- 2111817 TI - Purification and characterization of a beta-1,3-glucan binding protein from plasma of the crayfish Pacifastacus leniusculus. AB - The plasma of the crayfish Pacifastacus leniusculus contains a protein which is able to bind to laminarin (a soluble beta-1,3-glucan) and which has been isolated by two independent methods, affinity precipitation with a beta-1,3-glucan or immunoaffinity chromatography. The purified beta-1,3-glucan binding protein was homogenous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is a monomeric glycoprotein with a molecular mass of approximately 100,000 Da and an isoelectric point of approximately 5.0. Amino acid analysis showed a very high similarity with the amino acid composition of beta-1,3-glucan binding proteins recently purified from two insects, the cockroach Blaberus craniifer and the silkworm Bombyx mori. The N-terminal amino acid sequence was determined to be: H2N-Asp-Ala-Gly-X-Ala-Ser-Leu-Val-Thr-Asn-Phe Asn-Ser-Ala-Lys-Leu-X-X-Ly s--- Using monospecific rabbit polyclonal antibodies, the presence of this protein has also been shown within the blood cells. The purified beta-1,3-glucan binding protein did not show any peptidase or phenoloxidase activity but was able to enhance the activation of hemocyte-derived peptidase and prophenoloxidase only in the presence of the beta-1,3-glucan, laminarin, whereas mannan, dextran (alpha-glucan), or cellulose (beta-1,4-glucan) incubated with the beta-1,3-glucan binding protein had no effect on these enzyme activities. The beta-1,3-glucan binding protein could only be affinity precipitated from crayfish plasma by the beta-1,3-glucans laminarin or curdlan (an insoluble beta-1,3-glucan), while mannan or dextran did not bind to the beta 1,3-glucan binding protein. No hemagglutinating activity of the purified beta-1,3 glucan binding protein could be detected. PMID- 2111818 TI - Modulation of sphingolipid biosynthesis in primary cultured neurons by long chain bases. AB - Sphingolipid biosynthesis was studied in cultured murine cerebellar cells in the absence and presence of exogenous sphingosine homologues with different alkyl chain lengths (12, 18, and 24 carbon atoms). Labeling of cells with [14C]serine for 24 h indicated that endogenous sphingosine biosynthesis with incorporation of radiolabeled serine was inhibited by these long chain bases (0.5-50 microM) in a concentration-dependent manner; the inhibition was fully reversible after removal of the long chain bases from the culture medium. Metabolic labeling of neurons with [14C]galactose provided strong evidence that the cells were able to use the exogenous sphingosine homologues, irrespective of their alkyl chain length, as substrates for the biosynthesis of glycosphingolipids. When the biosynthetically inert sphingoid, azidosphingosine (5-50 microM), was fed to the cells, de novo sphingosine and glycosphingolipid biosynthesis were both strongly inhibited. PMID- 2111820 TI - Purification and characterization from bovine brain cytosol of a novel regulatory protein inhibiting the dissociation of GDP from and the subsequent binding of GTP to rhoB p20, a ras p21-like GTP-binding protein. AB - A novel regulatory protein for the rho proteins (rhoA p21 and rhoB p20), belonging to a ras p21/ras p21-like small molecular weight (Mr) GTP-binding protein (G protein) superfamily, was purified to near homogeneity from bovine brain cytosol and characterized. This regulatory protein, designated here as GDP dissociation inhibitor (GDI) for the rho proteins (rho GDI), inhibited the dissociation of GDP from rhoB p20 and the binding of guanosine 5'-(3-O thio)triphosphate (GTP gamma S) to the GDP-bound form of rhoB p20 but not of that to the guanine nucleotide-free form. The Mr value of rho GDI was estimated to be about 27,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and from the S value, indicating that rho GDI is composed of a single polypeptide without a subunit structure. The isoelectric point was about pH 5.7. rho GDI made a complex with the GDP-bound form of rhoB p20 with a molar ratio of 1:1 but not with the GTP gamma S-bound or guanine nucleotide-free form. rho GDI did not stimulate the GTPase activity of rhoB p20 and by itself showed neither GTP gamma S-binding nor GTPase activity. rho GDI was equally active for rhoA p21 and rhoB p20 but was inactive for other ras p21/ras p21-like G proteins including c-Ha-ras p21, smg p25A, and smg p21. rho GDI activity was detected in the cytosol fraction of various rat tissues. These results indicate that, in mammalian tissues, there is a novel type of regulatory protein specific for the rho proteins that interacts with the GDP-bound form of the rho proteins and thereby regulates the GDP/GTP exchange reaction of the rho proteins by inhibiting the dissociation of GDP from and the subsequent binding of GTP to them. Since there is a GTPase activating protein for the rho proteins stimulating the GTPase activity of the rho proteins in mammalian tissues, the rho proteins appear to be regulated at least by GTPase-activating protein and GDI in a dual manner. PMID- 2111819 TI - Binding and hydrolysis of guanine nucleotides by Sec4p, a yeast protein involved in the regulation of vesicular traffic. AB - The 23.5-kDa Sec4 protein is required for vesicular transport between the Golgi apparatus and the plasma membrane in Saccharomyces cerevisiae. In order to analyze its biochemical properties, we have purified the soluble pool of the wild type protein from an overproducing yeast strain. At 30 degrees C, Sec4p bound [35S] guanosine 5'-O-(thiotriphosphate) (GTP gamma S) with a rate of 0.18 min-1 in a reaction requiring micromolar concentration of free magnesium ions. The protein had high affinity for guanine nucleotides with Kd values for GTP gamma S and GTP of 3.7 nM and 3.5 nM, respectively, and that for GDP of 77 nM. The dissociation of [3H] GDP from Sec4p occurred with a rate of 0.21 min-1 suggesting that the association of GTP gamma S was the result of exchange for prebound GDP. The release of GTP from Sec4p was slow and correlated with a low inherent GTPase activity of 0.0012 min-1. By analogy with other classes of GTP binding proteins, both the nucleotide exchange and hydrolysis activities of Sec4p may be modulated in vivo to facilitate its role in the regulation of intercompartmental membrane traffic. PMID- 2111821 TI - A rare cause of facial nerve paralysis. PMID- 2111822 TI - Zinc deficiency and male infertility. PMID- 2111823 TI - Evaluation of tremor disorders. PMID- 2111824 TI - Balloon valvuloplasty for mitral stenosis. PMID- 2111825 TI - Genetic variation in chronic granulomatous disease. PMID- 2111826 TI - Glaucoma: screening, diagnosis, and therapy. PMID- 2111828 TI - The affirmation of human uniqueness. PMID- 2111827 TI - Thiazide diuretics: how real are the concerns? PMID- 2111829 TI - Prevention of gastrointestinal infection using immunobiological methods with milk fermented with Lactobacillus casei and Lactobacillus acidophilus. AB - The protective effect of feeding milk fermented with a mixture of Lactobacillus casei sp. and Lb. acidophilus sp. against Salmonella typhimurium infection in mice was compared with that obtained feeding milks fermented with these microorganisms individually. The survival rate obtained after oral infection with Sal. typhimurium was 100% in mice pretreated by feeding during 8 d with the mixture of Lb. casei and Lb. acidophilus fermented milks. Similar treatments with the individual milks were ineffective. Moreover, mice became more susceptible to infection with Sal. typhimurium after such treatment. The colonization of liver and spleen with the pathogen was markedly inhibited by the pretreatment with the mixture of fermented milk, while such inhibition was not observed using the Lb. casei and Lb. acidophilus milks. The highest levels of anti-salmonellae antibodies in serum and in intestinal fluid were found in the group of mice fed with the mixture and with Lb. casei fermented milk respectively. However, this latter milk was not effective in protecting against Sal. typhimurium. When the mice were first infected with Sal. typhimurium and then fed with the mixture of fermented milks, pathogen colonization was not prevented. The results suggest that the augmentation of resistance to salmonellae caused by the treatment with Lb. casei- + Lb. acidophilus-fermented milk was due to the anti-salmonellae protective immunity mainly mediated by the mucosal tissue. Milk fermented with this mixture could be used as an immunobiological method to prevent gastrointestinal infection. PMID- 2111830 TI - Effect of rumen-protected methionine and lysine on casein in milk when diets high in fat or concentrate are fed. AB - To examine the effect of supplying methionine and lysine on milk N composition, isoenergetic, isonitrogenous diets containing 50:50 with 3.9% added fat or 25:75 forage to concentrate with no added fat were fed with or without rumen-protected methionine and lysine to four primiparous and four multiparous early lactation (36 d in milk) Holstein cows in two 4 x 4 Latin squares. Diets contained 1.7 Mcal NE1 and were fed for ad libitum intake. Periods were 21 d. Rumen-protected methionine and lysine increased total N and casein N percentage with the 3.9% fat, but did not increase total N and casein N percentage with the diet without fat. Whey N percentage was greater with the no fat than with the 3.9% fat diet. Whey N percentage was not affected by adding amino acids. Nonprotein N percentage was greater for the diet with the 3.9% fat than with no fat. Proportions of casein N or whey N to total N were unaffected by treatments. Adding methionine and lysine to diets did not increase yields of total N and casein N. The 3.9% fat diet increased proportions of long-chain (C18:0 and C18:1) and decreased proportions of short- to medium-chain fatty acids (C8 to C16) in milk fat. Plasma nonesterified fatty acids and triglyceride concentrations were greater with the 3.9% fat as compared to the no fat diet. Methionine and lysine decreased plasma triglyceride concentrations with the 3.9% fat diet. Milk yields, DM intakes, and plasma glucose concentrations were unaffected by treatment. PMID- 2111831 TI - Factors to consider when selecting a culture of Lactobacillus acidophilus as a dietary adjunct to produce a hypocholesterolemic effect in humans. AB - Significant variations in bile tolerance and ability to assimilate cholesterol were observed among 12 cultures of Lactobacillus acidophilus of human origin. The degree of bile tolerance as measured by rapidity of growth in MRS broth supplemented with .3% oxgall could not be predicted by the rapidity of growth in the broth without oxgall. There was no apparent direct relationship between bile tolerance and cholesterol assimilation. However, among the cultures that most actively assimilated cholesterol, there were significant differences in bile tolerance. The most active cholesterol-assimilating cultures also varied in the ability to produce bacteriocins. A culture of L. acidophilus of human origin, which assimilates cholesterol, grows well in presence of bile, and produces bacteriocins can be selected for use as a dietary adjunct for humans. A culture of L. acidophilus possessing all these characteristics should have an advantage over one that does not in establishing and functioning in the intestinal tract to assimilate cholesterol. PMID- 2111832 TI - Listeria monocytogenes--threat to a safe food supply: a review. AB - Listeria monocytogenes can cause circling disease, encephalitis, meningitis, septicemia, and mastitis in dairy cattle. Shedding of the pathogen from the udder or contamination from the environment can lead to presence of L. monocytogenes in raw milk. Surveys indicate the pathogen is in about 4% of US raw milks. Although HTST pasteurization commonly inactivates L. monocytogenes, evidence suggests that under unusual circumstances minimal survival is possible. The pathogen grows well in liquid dairy products at 4 to 35 degrees C and achieves higher populations in chocolate than in unflavored milks. When present in cheese milk, growth of L. monocytogenes may be retarded but not stopped by lactic starter cultures. The pathogen is concentrated in the curd with only a small fraction of cells in milk appearing in whey. Once in curd, the behavior of the pathogen ranges from growth (feta cheese making) to death of most but not all cells (cottage cheese making). During ripening of cheese, the numbers of L. monocytogenes decrease gradually (as in Cheddar or Colby cheese), decrease precipitously early during ripening, and then stabilize (as in blue cheese) or increase markedly (as in Camembert cheese). Consumption of foods containing L. monocytogenes can lead to listeriosis in susceptible humans (adults with a compromised immune system), pregnant women, and infants). In large outbreaks of human listeriosis, mortality rates of ca. 30% are common. PMID- 2111833 TI - A comparison of glass cermet cement and amalgam restorations in primary molars. AB - The aim of this clinical study was to compare the efficacy of GCC with amalgam as a filling material in primary molars. Two hundred fifteen restorations were placed in the first and second primary molars of seventy-four patients, ranging in age from four to ten years. The overall failure rate of amalgam is lower than that of GCC, but not significantly different. In older children, amalgam has greater advantages. An advantage of GCC is the short time required to fill the cavity. This might be an important factor in young and/or difficult children. In these cases amalgam cannot be placed under optimal conditions and, therefore, the results are less satisfactory. GCC is a viable alternative filling material. PMID- 2111834 TI - Effectiveness of intradialytic parenteral nutrition in diabetic patients with end stage renal disease. PMID- 2111835 TI - Purification of recombinant ribonuclease T1 expressed in Escherichia coli. AB - A protocol for the rapid purification of ribonuclease T1 expressed from a chemically synthesized gene cloned into Escherichia coli is described. QAE ion exchange and Sephadex G-50 chromatography are used to give over 300 mg (88% yield) of pure ribonuclease T1 from 61 of liquid culture in 3 days. We also report a new absorption coefficient for RNase T1: E1%278 nm = 15.4. PMID- 2111836 TI - [Endometrial ossification. Apropos of 5 recent cases]. AB - Five cases of ossification of the endometrium that have been seen in the course of five years are reported. Special attention is paid to a case that occurred in the post-partum period. Several different hypotheses as to the aetiology of the pathology of this condition are discussed yet again; the only one that seems likely to be possible is that these ossifications start as metaplasias. The clinical, paraclinical and therapeutic angles are also dealt with. PMID- 2111837 TI - Diurnal variation of carbamazepine and carbamazepine-10,11-epoxide in plasma and saliva in children with epilepsy: a comparison between conventional and slow release formulations. AB - In order to overcome the problems of interdosage fluctuations of body fluid concentrations of carbamazepine, a slow-release formulation has been developed. In an open, controlled, within-patient study, the diurnal plasma concentrations of carbamazepine and its 10,11-epoxide were measured in 25 epileptic children first treated with conventional carbamazepine tablets (Tegretol) and then with the Tegretol slow-release preparation. The diurnal plasma concentration curves during treatment with the slow-release formulation showed significantly less variation over 24 hours than during treatment with the ordinary preparation, as measured by the fluctuation index. Mean concentration values also differed significantly, which is explained by a somewhat reduced bioavailability (22% less) of the slow-release formulation. There were no differences in efficacy and tolerability between the two formulations, but there was a clear-cut reduction of reported side effects, especially tiredness, on treatment with the slow-release formulation. For that reason, the slow-release formulation should be a major advantage in treating children with epilepsy, in order to avoid interference with cognitive functions. In 12 children, simultaneous measurements of the concentration of carbamazepine and its epoxide in saliva were made and compared with the plasma values. As expected, the concentration curves corresponded, indicating that saliva sampling is an appropriate alternative for monitoring the concentration of carbamazepine. All children remained on the slow-release preparation after the trial and were followed up for 12 months or more. PMID- 2111838 TI - Pseudomonas aeruginosa. Vaccines and immunotherapy. AB - Among opportunistic infections with gram-negative bacilli, those caused by Pseudomonas aeruginosa are associated with particularly high mortalities. Accordingly, considerable interest exists to develop immunotherapeutic or immunoprophylactic agents for this pathogen. In vitro as well as in vivo studies in animal models have demonstrated that LPS serotype-specific antibodies against P. aeruginosa confer protection. Thus, cell wall-derived LPS P. aeruginosa vaccines have been developed for active immunization. Toxic side effects from LPS and relatively slow immune response to active immunization in patients needing rapid protection have led to the development of high-titered anti-P. aeruginosa immunoglobulin G preparations. Passive immunotherapy with these polyclonal antibody preparations has shown promising results in animal models and in clinical pilot studies. More recently, murine and human monoclonal antibodies against P. aeruginosa have been developed. These preparations offer the potential advantage over polyclonal globulin preparations of low protein dosages and virtually unlimited supply. PMID- 2111839 TI - Expression of infectious viral particles by primary chimpanzee hepatocytes isolated during the acute phase of non-A, non-B hepatitis. AB - Liver wedge biopsies were obtained from chimpanzees during the acute phase of experimental non-A, non-B hepatitis infections. Primary chimpanzee hepatocytes were maintained for over 4 weeks in vitro with a serum-free medium supplemented with growth factors and hormones. The de novo synthesis and secretion of plasma proteins characteristic for differentiated primate hepatocytes were sustained under these culture conditions. Immunocytochemical staining for a non-A, non-B hepatitis-associated antigen revealed expression of this cytoplasmic marker during the culture period, indicating a persistence of the infection in vitro. Tissue culture medium derived from the hepatocyte cultures was used to inoculate a nonimmune chimpanzee. The animal subsequently displayed an increase in the serum levels of alanine aminotransferase, the development of histopathologic alterations indicative of viral hepatitis, and the appearance of liver cell cytoplasmic tubules diagnostic for non-A, non-B hepatitis. Concentrated tissue culture medium examined by electron microscopy contained virus-like particles with an average diameter of 39-46 nm, which exhibited an envelope and inner 37-nm core structure. PMID- 2111840 TI - Enhanced killing of group B streptococci in vitro by penicillin and opsonophagocytosis with intravenous immunoglobulin. AB - Combined effects of intravenous immunoglobulin (IVIG) and antibiotics in killing bacteria are of interest with broadening clinical use of IVIG. Since the kinetics of killing by these agents differ and each may influence the outcome of the other, it is difficult to evaluate combination effects in vitro. Conditions were developed to measure killing of group B streptococci (GBS), type III strain M732, by an opsonic mixture with IVIG, fresh serum, and human polymorphonuclear leukocytes (PMNL) with or without penicillin. Bacterial killing was observed with the opsonic IVIG mixture, penicillin, and the opsonic IVIG mixture plus penicillin at 1 h. The effect of the combination was greater than the sum of the effects of two separate incubations. The enhanced killing was evident for up to 18 h. By 24 h, the killing by the combination was no greater than that by penicillin alone. A similar pattern of GBS killing was observed with cord blood PMNL, six different GBS type III strains, and pretreatment of GBS with either IVIG or penicillin. These effects suggest that the combination of IVIG and penicillin has potential for use in the treatment of neonatal GBS infections. PMID- 2111842 TI - The $100,000 funeral. PMID- 2111841 TI - Deficit financing in medical care. PMID- 2111843 TI - The 1989 OBRA legislation: implications for physicians. PMID- 2111844 TI - Random walking. PMID- 2111845 TI - Polymerization of amino acids containing nucleotide bases. AB - We have prepared the nucleoamino acids 1-(3'-amino,3'-carboxypropyl)uracil (3) and 9-(3'-amino,3'-carboxypropyl)adenine (4) as (L)-enantiomers and as racemic mixtures. When 3 or 4 is suspended in water and treated with N,N' carbonyldiimidazole, peptides are formed in good yield. The products formed from the (L)-enantiomers are hydrolyzed to the monomeric amino acids by pronase. Attempts to improve the efficiency of these oligomerizations by including a polyuridylate template in the reaction mixture were not successful. Similarly, oligomers derived from the (L)-enantiomer of 3 did not act as templates to facilitate the oligomerization of 4. PMID- 2111846 TI - Evolution of the mitochondrial genetic code. III. Reassignment of CUN codons from leucine to threonine during evolution of yeast mitochondria. AB - Yeast mitochondria use UUR as the sole leucine codons. CUN, universal leucine codons, are read as threonine by aberrant threonine tRNA with anticodon sequence (UAG). The reassignment of CUN codons to threonine during yeast mitochondrial evolution could have proceeded by the disappearance of CUN codons from the reading frames of messenger RNA, through mutation mainly to UUR leucine codons as a result of AT pressure. We suggest that this was accompanied by a loss of leucine-accepting ability of tRNA Leu(UAG). This tRNA could have then acquired threonine-accepting activity through the appearance of an additional threonyl tRNA synthetase. CUN codons that subsequently appeared from mutations of various other codons would have been translated as threonine. This change in the yeast mitochondrial genetic code is likely to have evolved through a series of nondisruptive nucleotide substitutions that produced no widespread replacement of leucine by threonine in proteins as a consequence. PMID- 2111847 TI - Evolution of the mitochondrial genetic code. IV. AAA as an asparagine codon in some animal mitochondria. AB - Differences in assignments from those in the universal genetic code occur in codes of mitochondria. In this report, the published sequences of the mitochondrial genes for COI and ND1 in a platyhelminth (Fasciola hepatica) are examined and it is concluded that AAA may be a codon for asparagine instead of lysine, whereas AAG is the sole codon for lysine in this species. PMID- 2111848 TI - Vertebrate protamine gene evolution I. Sequence alignments and gene structure. AB - The availability of the amino acid sequence for nine different mammalian P1 family protamines and the revised amino acid sequence of the chicken protamine galline (Oliva and Dixon 1989) reveals a much close relationship between mammalian and avian protamines than was previously thought (Nakano et al. 1976). Dot matrix analysis of all protamine genes for which genomic DNA or cDNA sequence is available reveals both marked sequence similarities in the mammalian protamine gene family and internal repeated sequences in the chicken protamine gene. The detailed alignments of the cis-acting regulatory DNA sequences shows several consensus sequence patterns, particularly the conservation of a cAMP response element (CRE) in all the protamine genes and of the regions flanking the TATA box, CAP site, N-terminal coding region, and polyadenylation signal. In addition we have found a high frequency of the CA dinucleotide immediately adjacent to the CRE element of both the protamine genes and the testis transition proteins, a feature not present in other genes, which suggests the existence of an extended CRE motif involved in the coordinate expression of protamine and transition protein genes during spermatogenesis. Overall these findings suggest the existence of an avian-mammalian P1 protamine gene line and are discussed in the context of different hypotheses for protamine gene evolution and regulation. PMID- 2111849 TI - Amino acid sequences of stomach and nonstomach lysozymes of ruminants. AB - Complete amino acid sequences are presented for lysozymes c from camel and goat stomachs and compared to sequences of other lysozymes c. Tree analysis suggests that the rate of amino acid replacement went up as soon as lysozyme was recruited for the stomach function in early ruminants. The two lysozymes from goat stomach are the products of a gene duplication that probably took place before the divergence of cow, goat, and deer about 25 million years ago. Partial sequences of three lysozymes from goat tears indicated that (a) the goat tear family of lysozymes may have diverged from the stomach lysozyme family by an ancient duplication and (b) later duplications are probably responsible for the multiple forms of tear and milk lysozymes in ruminants. PMID- 2111850 TI - Comparison of dinucleotide frequency and codon usage in Toxoplasma and Plasmodium: evolutionary implications. AB - The weight-averaged observed/expected dinucleotide frequencies for the sum total of the coding regions of five Toxoplasma genes were compared with the same parameters previously determined for the coding regions of 21 Plasmodium genes. In addition, codon usage in the five Toxoplasma genes was compared with that in the 21 Plasmodium genes, and the percent distribution of amino acids in the Toxoplasma protein pool and the Plasmodium protein pool were compared with that in a general protein pool of 314 proteins. The results are consistent with the hypothesis that, contrary to currently held opinion, the genera Toxoplasma and Plasmodium are not especially closely related. PMID- 2111851 TI - Random walking. PMID- 2111852 TI - Nonrandomness in prebiotic peptide synthesis. AB - We have synthesized and studied the properties of phosphoanhydrides of alanine with guanosine monophosphate, uridine monophosphate, and adenosine monophosphate. This series of compounds allowed us to investigate the specificity of peptide bound formation in a reaction that could have taken place on the prebiotic earth. We asked whether the intrinsic reactivity of the amino acids, the nature of the nucleotide in the anhydride, or the complementary polynucleotide template influences the specificity of the peptide synthesis reaction. We observed that the differential reactivity of the amino acids results in nearest-neighbor preferences during the peptide synthesis, whereas the nature of the nucleotides and the presence of complementary polynucleotides had no influence on the specificity. These results suggest that some peptides would have been more abundant than others on the prebiotic earth and have implications for the study of the origins of the genetic code and protein synthesis. PMID- 2111853 TI - The fossil record and estimating divergence times between lineages: maximum divergence times and the importance of reliable phylogenies. AB - Bounded estimates on divergence times between lineages are crucial to the calculation of absolute rates of molecular evolution. Upper (minimum) bounds on divergence times are easily estimated based on earliest fossil finds. Lower (maximum) bounds are more difficult to estimate; the age of putative ancestors may be used, though in practice it is virtually impossible to distinguish ancestors from primitive sister groups, which do not, of logical necessity, constitute lower bounds on divergence times. Two relatively new approaches to estimating lower bounds directly assess the incompleteness of the fossil record. The first uses taphonomic control groups to distinguish real absences from nonpreservation, while the second, and probably more powerful, uses the quality of the fossil record to estimate confidence intervals on the bases of stratigraphic ranges. For some groups, especially vertebrates, the inclusion or exclusion of problematic fossils can dramatically affect estimated lower bounds on divergence times, often swamping the uncertainties due to the incompleteness of the fossil record and/or correlation and dating errors. When datable paleogeographic events reflect ancient divisions of faunas, a lower bound on the divergence time of species within a fauna can be established based on the geologic, rather than fossil, record. The fossil records of hominids, eutherian mammals, echinoids, and geese are used as examples. PMID- 2111854 TI - Phylogeny of the major tetrapod groups: morphological data and divergence dates. AB - The phylogeny of the major groups of tetrapods (amphibians, reptiles, birds, and mammals) has until recently been poorly understood. Cladistic analyses of morphological data are producing new hypotheses concerning the relationships of the major groups, with a focus on the identification of monophyletic groups. Molecular phylogenies support some of these views and dispute others. Geological dates of the major evolutionary branching points are recalculated on the basis of the cladograms and new fossil finds. PMID- 2111855 TI - Molecular homology and DNA hybridization. AB - We reviewed the concept of homology, which can broadly be defined as a correspondence between characteristics that is caused by continuity of information (Van Valen 1982). The concept applies widely in molecular biology when correspondence is taken to mean a genetic relationship resulting from a unique heritable modification of a feature at some previous point in time. Such correspondence can be established for features within a single organism as well as between organisms, making paralogy a valid form of molecular homology under this definition. Molecular homology can be recognized at a variety of organizational levels, which are interdependent. For example, the recognition of homology at the site level involves a statement of homology at the sequence level, and vice versa. This hierarchy, the potential for nonhomologous identity at the site level, and such processes as sequence transposition combine to yield a molecular equivalent to complex structural homology at the anatomical level. As a result, statements of homology between heritable units can involve a valid sense of percent homology. We analyzed DNA hybridization with respect to the problems of recognizing homology and using it in phylogenetic inference. Under a model requiring continuous divergence among compared sequences, DNA hybridization distances embed evolutionary hierarchy, and groups inferred using pairwise methods of tree reconstruction are based on underlying patterns of apomorphic homology. Thus, symple-siomorphic homology will not confound DNA hybridization phylogenies. However, nonhomologous identities that act like apomorphic homologies can lead to inaccurate reconstructions. The main difference between methods of phylogenetic analysis of DNA sequences is that parsimony methods permit hypotheses of nonhomology, whereas distance methods do not. PMID- 2111856 TI - DNA/DNA hybridization studies of the carnivorous marsupials. I: The intergeneric relationships of bandicoots (Marsupialia: Perameloidea). AB - A complete suite of comparisons among six bandicoot species and one outgroup marsupial was generated using the hydroxyapatite chromatography method of DNA/DNA hybridization; heterologous comparisons were also made with three other bandicoot taxa. Matrices of delta Tm's, delta modes, and delta T50Hs were generated and corrected for nonreciprocity, homoplasy, and, in the case of delta Tm's, normalized percent hybridization; these matrices were analyzed using the FITCH algorithm in Felsenstein's PHYLIP (version 3.1). Uncorrected and nonreciprocity corrected matrices were also jackknifed and analyzed with FITCH to test for consistency. Finally, sample scores for delta Tm, delta mode, and delta T50H matrices were bootstrapped and then subjected to phylogenetic analysis. These manipulations were carried out, in part, to address criticisms of the statistics used to summarize DNA/DNA hybridization (especially T50H) and the method itself. However, with the exception of an unresolved trichotomy among the two Echymipera species and Peroryctes longicauda, all trees showed the same branchpoints. Except in the case of the tree generated from reciprocal-corrected delta Tm data, nodes were stable under jackknifing; and, again excepting the above-mentioned trichotomy, all nodes were supported by 95% or more of the bootstrapped trees. These results suggest that, despite arguments to the contrary, all three summary statistics can be valid for DNA/DNA hybridization data. Of taxonomic interest is the placement of Echymipera spp. and Peroryctes longicauda together and separate from the more distant Peroryctes raffrayanus; the genus Peroryctes is thus at least paraphyletic. The trees further grouped Echymipera-plus-Peroryctes as the sister group of Isoodon-plus-Perameles. Limited hybridizations with Macrotis lagotis suggest that its current position as representative of an entirely distinct family of perameloids is correct. PMID- 2111857 TI - Conservation of intron position indicates separation of major and variant H2As is an early event in the evolution of eukaryotes. AB - Genomic clones of Drosophila and Tetrahymena histone H2A variants were isolated using the corresponding cDNA clones (van Daal et al. 1988; White et al. 1988). The site corresponding to the initiation of transcription was defined by primer extension for both Drosophila and Tetrahymena genomic sequences. The sequences of the genomic clones revealed the presence of introns in each of the genes. The Drosophila gene has three introns: one immediately following the initiation codon, one between amino acids 26 and 27 (gln and phe), and one between amino acids 64 and 65 (glu and val). The Tetrahymena gene has two introns, the positions of which are identical to the first two introns of the Drosophila gene. The chicken H2A.F variant gene has been recently sequenced and it contains four introns (Dalton et al. 1989). The first three of these are in the same positions as the introns in the Drosophila gene. The fourth intron interrupts amino acid 108 (gly). In all cases the sizes and the sequences of the introns are divergent. However, the fact that they are in conserved positions suggests that at least two of the introns were present in the ancestral gene. A phylogenetic tree constructed from the sequences of the variant and major cell cycle-regulated histone H2A proteins from several species indicates that the H2A variant proteins are evolutionarily separate and distinct from the major cell cycle-regulated histone H2A proteins. The ancestral H2A gene must have duplicated and diverged before fungi and ciliates diverged from the rest of the eukaryote lineage. In addition, it appears that the variant histone H2A proteins analyzed here are more conserved than the major histone H2A proteins. PMID- 2111858 TI - Small ribosomal subunit RNA sequences, evolutionary relationships among different life forms, and mitochondrial origins. AB - A tree was constructed from a structurally conserved area in an alignment of 83 small ribosomal subunit sequences of eukaryotic, archaebacterial, eubacterial, plastidial, and mitochondrial origin. The algorithm involved computation and optimization of a dissimilarity matrix. According to the tree, only plant mitochondria belong to the eubacterial primary kingdom, whereas animal, fungal, algal, and ciliate mitochondria branch off from an internal node situated between the tree primary kingdoms. This result is at variance with a parsimony tree of similar size published by Cedergren et al. (J Mol Evol 28:98-112, 1988), which postulates the mitochondria to be monophyletic and to belong to the eubacterial primary kingdom. The discrepancy does not follow from the use of conflicting sequence alignments, hence it must be due to the use of different treeing algorithms. We tested our algorithm on a set of sequences resulting from a simulated evolution and found it capable of faithfully reconstructing a branching topology that involved very unequal evolutionary rates. The use of more limited or more extended areas of the complete sequence alignment, comprising only very conserved or also more variable portions of the small ribosomal subunit structure, does have some influence on the tree topology. In all cases, however, the nonplant mitochondria seem to branch off before the emergence of eubacteria, and the differences are limited to the branching pattern among different types of mitochondria. PMID- 2111859 TI - [Eight cases of intracranial arteriovenous malformations treated by conventional radiation therapy]. AB - We conducted radiotherapy in 8 cases of intracranial arteriovenous malformation that had difficult embolectomy and other surgery from 1983 to October, 1988. The results in 6 cases of dural arteriovenous malformation at the cavernous sinus were "marked effect" in 4 cases, "relapse" in 1 case, and "no effect" in 1 case. One case of dural arteriovenous malformation at the sigmoid venous sinus demonstrated only slight irradiation effect. No irradiation effect was observed in 1 case of cerebral arteriovenous malformation. PMID- 2111860 TI - Effect of chronic renal failure on high-density lipoprotein kinetics. AB - Plasma lipid and lipoprotein concentration and high density lipoprotein (HDL) kinetics were determined in control subjects and patients with chronic renal failure (CRF). Results demonstrated that plasma triglyceride (TG) concentration was significantly higher (P less than 0.001) in patients with CRF, associated with a significant increase in plasma VLDL-cholesterol (P less than 0.002) and a significant decrease (P less than 0.05) in plasma HDL-cholesterol concentration. The rate of removal of 125I-apoAI/HDL from plasma was slower (P less than 0.001) in the patients with CRF, resulting in an increase in the residence time of 125I apoAI/HDL (P less than 0.001) and a decrease in the fractional catabolic rate (P less than 0.001). Since plasma apoAI concentration was lower in patients with CRF, total apoAI/HDL synthetic rate was also significantly (P less than 0.05) decreased. These data provide support for the view that low plasma HDL cholesterol concentrations in patients with CRF are related to decreases in the synthetic rate of apoAI/HDL. PMID- 2111861 TI - Eicosanoid synthesis in human peritoneal macrophages stimulated with S. epidermidis. AB - Peritoneal macrophages isolated from CAPD patients phagocytosed S. epidermidis in a time dependent manner. Coincident with a maximum phagocytic uptake of 56% by 12 hours, there was secretion of a significant amount of neutral protease (1.37 +/- 0.2 mg [3H]-casein degraded/10(6) cells, P = 0.05). In contrast to these delayed effects, coincubation of PMO with S. epidermidis resulted in a significant increase in both LTB4 and LTC4 synthesis above that of controls, with 6.33 +/- 1.20 ng LTB4/10(6) cells (P less than 0.01) and 2.06 +/- 0.68 ng LTC4/10(6) cells (P = 0.014) being generated by three hours. The generation of these lipoxygenase products was both time and dose dependent, and the rapid production and release of the potently chemotactic LTB4 is consistent with the observed clinical response, where a rapid influx of PMN into the peritoneal cavity occurs during episodes of peritonitis, while the generation of LTC4 may contribute to the hyperemia and interstitial edema. In contrast, although there was a time dependent rise in cyclooxygenase product generation by unstimulated cells, a dose dependent inhibition of synthesis was clearly demonstrated when cells were incubated with bacteria, with a mean 40% reduction in generation of PGE2 and a mean 34% reduction in TXB2 generation (P = 0.01 and P less than 0.025, respectively). It was demonstrated that the inhibition was not due to lack of available substrate and that the generation of eicosanoids was unrelated to phagocytosis, bacterial/PMO contact or bacterial surface characteristics. Instead, the observed effect of S. epidermidis on the PMO was attributable to a secreted bacterial product. PMID- 2111863 TI - Cardiovascular effects of n-6 fatty acids. AB - N-6 fatty acids comprise linoleic, dihomo-gamma-linolenic and arachidonic acid. Each of these polyunsaturated fatty acids display an individual pattern of cardiovascular effects. Moreover, the supplementation of the diet with one of these n-6 fatty acids results in a concomitant effect on the resorption, distribution and metabolism of the other n-6 fatty acids. While linoleic acid is abundant in our diet, the other n-6 fatty acids are only found in minute amounts. Accordingly, the effects with linoleic acid are less impressive, but more complex (e.g. lowering of plasma cholesterol, inhibition of renin) than with both other n 6 fatty acids. Linoleic acid, being no direct prostaglandin precursor, displays a variety of effects on the prostaglandin cascade, while dihomo-gamma-linolenic acid gives rise to 1-series prostaglandins and arachidonic acid to prostaglandins (eicosanoids) of the 2-series. The quality and quantity of prostaglandins formed, contribute essentially to the cardiovascular effects of the individual n-6 fatty acids. PMID- 2111862 TI - Upregulation of a lymphoid serine protease in kidney allograft recipients. AB - The presence of a putative, cytotoxicity-linked lymphoid serine esterase (SE) has been studied in 79 kidney graft recipients. Peripheral blood lymphocytes (PBL) bearing an N-alpha-benzyloxy carbonyl-L-lysine thiobenzyl ester (BLT)-specific SE were evaluated by a novel cytochemical staining method. A characteristic of post allograft patients was an increased presence of SE containing granules in PBL. In 46 patients with stable graft function SE + PBL were 33.41 +/- 10.34% (controls: 26.30 +/- 5.22%, P less than 0.0025), SE + CD4+ 4.32 +/- 3.85% (controls 2.13 +/- 1.52%, P less than 0.0025) and SE + CD8+ T cells 47.68 +/- 18.64% (controls: 28.50 +/- 6.50%, P less than 0.0005). In those graft recipients undergoing a rejection episode a marked upregulation of SE activity could be observed when compared to the stable graft group: SE + PBL were 59.91 +/- 10.89% (P less than 0.0005), SE + CD8+ 74.30 +/- 10.79% (P less than 0.0005) and SE + CD4+ T cells 28.56 +/- 13.50% (P less than 0.0005). In 10 cases this increase of SE activity was observed with a time lag of up to 37 days prior to the onset of clinical or biopsy proven rejections, promptly decreasing in response to methylprednisolone antirejection therapy. In patients with recurrent rejection episodes and subsequent graft loss, a repeating increase of SE activity indicated a failure of therapeutic agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111864 TI - Preliminary experiments of possible uses in medicine of novel plastic hollow fibers for transmission of CO2 radiation. AB - Plastic hollow fibers for the transmission of CO2 laser energy in curved paths were produced by plating the inner surface of plastic tubes with a metal film and dielectric film upon that. These fibers can transmit high power, up to 40 W at the outlet, with high transmission yield even through several bendings. To demonstrate a possible use of the fibers, they were checked for their influence on live tissues of dogs. Incisions were made in the liver, and ulcers in the dogs' stomachs were treated. The fibers were inserted into the stomach through the esophagus. Complete healing was observed after 4 weeks. PMID- 2111865 TI - Do imipramine and dihydroergosine possess two components--one stimulating 5-HT1 and the other inhibiting 5-HT2 receptors? AB - The mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-induced stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT1 receptor sites, but not by ritanserin, a specific 5-HT2 receptor antagonist. (-) Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. Neither imipramine nor dihydroergosine were able to stimulate the 5-HT syndrome in the animals pretreated with p-chlorophenylalanine. As expected, 8-OH-DPAT, a selective 5-HT1A receptor agonist, stimulated, and 5-HT1B agonists CGS 12066B and 1-(trifluoromethylphenyl)piperazine (TFMPP) failed to stimulate the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer than after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for 3H-ketanserin binding sites than imipramine. The results suggest that imipramine and dihydroergosine possess two components--one stimulating the 5-HT syndrome in rats by a presynaptic, presumably 5-HT1A-mediated mechanism, and the other inhibiting 5-HT2 binding sites. PMID- 2111866 TI - High affinity dopamine reuptake inhibitors as potential cocaine antagonists: a strategy for drug development. AB - The addictive and euphorogenic effects of cocaine are thought to result primarily from inhibition of dopamine reuptake. Although the potency of cocaine-like drugs as inhibitors of DA reuptake is highly correlated with their potency as reinforcers in animals, several potent DA reuptake blockers (bupropion, nomifensine, benztropine, and mazindol) have not been reported to produce addiction or euphoria in humans. Based on these observations in humans, DA reuptake inhibitors are classified into two groups; type 1 blockers, which produce addiction and euphoria, and type 2 blockers, which do not. Given that type 1 and type 2 blockers act at the same site (the DA transporter), the author suggests that type 2 agents may antagonize the effects of cocaine, and might prove useful in the treatment of cocaine addiction. PMID- 2111867 TI - The prostacyclin analogue taprostene and recombinant human superoxide dismutase increase the permanent survival rate of endotoxemic rats. AB - The permanent survival rate of endotoxemic rats was studied. In 40 untreated control rats the survival rate 7 days after the endotoxin administration was 33%. The survival rate was increased to 40% with recombinant human superoxide dismutase (r-HSOD), to 55% (p less than 0.05) with the prostacyclin analogue Taprostene and to 70% (p less than 0.01) with the combination of r-HSOD and Taprostene (20 rats for each treatment group). r-HSOD and Taprostene provide significant and permanent protection in rat endotoxic shock. PMID- 2111868 TI - Development of a novel scintillation proximity radioimmunoassay for platelet activating factor measurement: comparison with bioassay and GC/MS techniques. AB - A novel, facile and sensitive scintillation proximity radioimmunoassay (SPRIA) for quantitation of PAF has been developed. No separation of antibody bound [3H]PAF from free [3H]PAF is required as the assay employs protein A - coated fluomicrospheres (beads containing scintillant). The assay system was suitable for the quantitation of 0.03 to 2 pmol of 1-hexadecyl-2-acetyl-sn-glycero-3- phosphocholine. The cross-reactivity was high with 1-alkyl-2-acetyl-sn-glycero-3 phosphocholine but was very low with PAF analogs such as 1-alkyl- and 1-acyl-2 lyso-sn-glycero-3-phosphocholine, 1-acyl-2-acetyl-sn-glycero-3-phosphocholine, and 1-alk-1'-enyl-2-acetyl-sn-glycero-3-phosphocholine. The specificity of SPRIA was higher than that of bioassay (platelet degranulation assay). PAF receptor antagonists (L-652,731, WEB2086, and FR900452) at up to 10 nmol per tube had no affect on the SPRIA. These observations indicate that the specificity of the PAF antibody is quite different from that of the platelet receptor. The values obtained using SPRIA for the measurement of PAF produced in polymorphonuclear leukocytes with stimuli are comparable to those obtained by SIM/GC/MS analysis. PMID- 2111869 TI - In vitro effects of thyroxine on the mechanical properties of erythrocytes. AB - In vitro effects of thyroxine on erythrocyte deformability and mechanical fragility were observed. Deformability of erythrocytes was improved in a dose dependent manner by thyroxine. Mechanical hemolysis was found to be lower if thyroxine was included in erythrocyte suspensions at concentrations close to the physiological levels (10(-9)M). These changes might be related to the alterations of intracellular calcium concentration, as in the erythrocyte suspensions containing 10(-9)M thyroxine, intracellular calcium concentration was found to be 30 times lower than the control suspensions which did not contain thyroxine. Thyroxine also reduced the mechanical hemolysis ratio in calcium loaded cells. These observations suggest that thyroxine might play some role in the regulation of the mechanical properties of erythrocytes which might be mediated via the effects on calcium metabolism. PMID- 2111870 TI - Mannitol-induced acute renal failure. AB - Mannitol is widely used to reduce intracranial pressure and is protective against ischemic and nephrotoxic acute renal failure. However, the capacity of this seemingly innocuous agent to produce acute renal failure is not well recognized. We report herein the clinical course of 8 cases of mannitol-induced acute renal failure. In addition, we reviewed all previously reported cases of mannitol induced renal failure. In the present series, acute oliguric renal failure developed within 3.5 +/- 1.1 (mean +/- SD) days after receiving daily and total mannitol doses of 189 +/- 64 g and 626 +/- 270 g, respectively, over 3.5 +/- 1.5 days. The peak serum creatinine was 5.7 +/- 2.7 mg/dl and peak osmolal gap was 74 +/- 39 mOsm/kg water. Renal tubular epithelial cells containing vacuoles were seen in the urinary sediments of 6 patients. Renal function improved rapidly upon discontinuation of mannitol and/or removal of mannitol by hemodialysis. In those previously reported cases in which the baseline renal function was normal, acute renal failure developed after receiving total mannitol doses of 1171 +/- 376 g. The peak osmolal gap was 107 +/- 17. In contrast, in those with underlying renal compromise, renal function worsened after a total mannitol dose of 295 +/- 143 g. The pathogenesis of mannitol-induced renal failure is not yet established but may be associated with renal vasoconstriction produced by high concentrations of mannitol. This may be averted in clinical practice by monitoring the osmolal gap, rather than serum osmolality alone, when using mannitol infusions for the treatment of intracranial hypertension. PMID- 2111871 TI - Serogrouping of oral Streptococcus intermedius. AB - Employing twenty fresh oral isolates of Streptococcus intermedius, studies were carried out to characterize serological relations among the isolates and also between the isolates and the strains of bacterial species closely related to S. intermedius. The Rantz-Randall extracts from the cells were used as antigens. The anti-rabbit serum raised against S. intermedius ATCC 27335T reacted with the cell extracts from only three strains of the isolates, which were designated serogroup I strains. The other isolates were classified into four serogroups, I, III, IV, and V, which specifically reacted with the cell extracts from the homologous serogroup strains. However, the serogroup II antiserum formed in immunodiffusion a common precipitin line between the extracts from the cells of serogroups II and I. The serogroups I, III, IV, and V antisera reacted with none of the extracts from the bacterial cells closely related to S. intermedius, which included Streptococcus anginosus ATCC 33397T, Streptococcus constellatus ATCC 27823T, three NCTC strains of "Streptococcus milleri," and three ATCC strains of Streptococcus MG. The precipitin line formed by the homologous reaction of the serogroup II antiserum was found to be a reaction of identity with that formed by the extract from "S. milleri" NCTC 10708. Conversely, the antiserum against NCTC 10708 strain did not react with the cell extracts of serogroup II. PMID- 2111873 TI - Chronic diabetes harms islet-cell transplants by inhibiting graft vascularisation. AB - Pancreatic islet-cell transplantation is very effective in treating insulin dependent diabetes in animals but has had no success in humans. Most animals have received islet-cell grafts after short periods of diabetes, while patients have been grafted after years of disease. We have shown a detrimental effect of chronic diabetes on islet-cell grafts in animals, which is at least partially ameliorated by peritransplant insulin infusion. We suggest that this detrimental effect may be mediated by poor vascularisation. There is further evidence from wound healing and tumour grafting experiments, and from the recent insulin pump studies in humans to support our hypothesis. To be successful, islet-cell grafts in humans may have to be performed earlier in the course of the disease and be preceded by a period of accurate diabetic control. PMID- 2111872 TI - Proposals of Sphingomonas paucimobilis gen. nov. and comb. nov., Sphingomonas parapaucimobilis sp. nov., Sphingomonas yanoikuyae sp. nov., Sphingomonas adhaesiva sp. nov., Sphingomonas capsulata comb. nov., and two genospecies of the genus Sphingomonas. AB - Based on the partial nucleotide sequence analysis of 16S ribosomal ribonucleic acid (rRNA), presence of unique sphingoglycolipids in cellular lipid, and the major type of ubiquinone (Q10), we propose Sphingomonas gen. nov. with the type species Sphingomonas paucimobilis (Holmes et al, 1977) comb. nov. From the homology values of deoxyribonucleic acid-deoxyribonucleic acid hybridization and the phenotypic characteristics, three new species, Sphingomonas parapaucimobilis, Sphingomonas yanoikuyae, Sphingomonas adhaesiva, and one new combination, Sphingomonas capsulata, are described. S. parapaucimobilis JCM 7510 (= GIFU 11387), S. yanoikuyae JCM 7371 (= GIFU 9882), and S. adhaesiva JCM 7370 (= GIFU 11458) are designated as the type strains of the three new species. Emended description of the type strain of S. capsulata is presented. PMID- 2111874 TI - HIV-related knowledge and behaviors among high school students--selected U.S. sites, 1989. PMID- 2111875 TI - Tickborne diseases--Georgia, 1989. PMID- 2111876 TI - Screening for tuberculosis and tuberculous infection in high-risk populations. Recommendations of the Advisory Committee for Elimination of Tuberculosis. PMID- 2111877 TI - The use of preventive therapy for tuberculous infection in the United States. Recommendations of the Advisory Committee for Elimination of Tuberculosis. PMID- 2111878 TI - Effect of the calcium ionophore A23187 on glucose uptake in slow and fast skeletal muscles of rats. PMID- 2111879 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 25-1990. Abdominal pain and vomiting in a 64-year-old man with chronic malabsorption and diarrhea. PMID- 2111880 TI - Rationing medical progress. The way to affordable health care. PMID- 2111881 TI - Eosinophilia from food dye added to enteral feedings. PMID- 2111882 TI - [The treatment of children with slow growth: how much of what for whom?]. PMID- 2111883 TI - [Shock wave lithotripsy of gallstones]. PMID- 2111884 TI - Prostaglandins, angiotension II, and proteinuria. AB - Nonsteroidal anti-inflammatory drugs, especially indomethacin, have variable effects on proteinuria when used alone, but can dramatically reduce proteinuria if combined with diuretics and sodium restriction. Reduction of angiotensin II concentrations in plasma and kidney following angiotensin-converting enzyme inhibition also reduces proteinuria, not only in nephrotic conditions but also in diverse diseases, including diabetes mellitus, glomerulosclerosis following subtotal nephrectomy, and membranous nephropathy. The reduction of proteinuria appears independent of decrements in blood pressure since other hypotensive agents do not alter proteinuria in these conditions. PMID- 2111885 TI - 'Neurosecretion' by synaptic terminals and glandular discharge in the endocrine pancreas. Application of tannic acid to the teleost Xiphophorus helleri. AB - Nerve fibers within the large pancreatic islet of Xiphophorus helleri are apparently of a single type and form typical, well-differentiated synapses with the endocrine gland cells. A histochemical test for cholinesterases generates reaction product in association with the outer surfaces of the neuronal membranes. Two categories of presumptive secretory inclusions are present in the fiber terminals: secretory granules usually 80-120 nm in diameter have a wide distribution within the fibers, whereas electron-lucent synaptic vesicles 30-60 nm across often cluster adjacent to membrane thickenings and differentiated clefts. Infusion of tannic acid in high-K+ saline enabled sites of granule exocytosis to be visualized. These presumed sites of neuropeptide discharge were associated with morphologically undifferentiated regions of the terminal membranes. Tannic acid also facilitated the detection of exocytosis, involving granules of endocrine gland cells; discharged secretory material exposed to this agent retains immunoreactivity at a reduced level. PMID- 2111886 TI - Hypothalamic aromatase activity in male and female rats during juvenile peripubertal development. AB - Evidence exists that testosterone (T) regulates brain aromatase activity in adult rats. It is not known, however, whether the activity and/or its regulation by androgens change during the time of puberty. In the present study, we examined the change in basal aromatase activity associated with puberty in both male and female rats. We also assessed the influence of castration and treatment with a nonaromatizable androgen, dihydrotestosterone (DHT), on the hypothalamic aromatase system during juvenile and peripubertal development of male rats. Aromatase activity was estimated by both quantifying the 3H2O released from [1 beta-3H]T and by isolating the estrogen product(s) by thin-layer chromatography (TLC) after incubations with [1,2,6,7-3H]T. 5 alpha-Reductase activity was determined simultaneously in the male hypothalamus by TLC using [1 alpha-3H]T as the substrate. Aromatase activity was linear with time of incubation and amount of tissue used. It was detected at similar levels in both tissue fragments and acutely dispersed cell preparations. Expression in the latter, but not the former required the addition of NADPH. Intracellular rates of both aromatase and 5 alpha reductase activities were highest in the mitochondrial-microsomal fraction. In both males and females the time of puberty was associated with a decrease in hypothalamic aromatase activity. In females, this drop was found to occur between the days of first proestrus and first estrus. In males, it occurred between 48 and 68 days of age (i.e., after the animals had reached puberty, as assessed by the presence of free sperm in the seminiferous tubules).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111887 TI - Diabetes-induced alterations of reproductive and adrenal function in the female rat. AB - Diabetes interferes with reproductive function in laboratory animals. Previous studies in female diabetic rats have not resolved if the reproductive abnormalities observed are at the hypothalamic, pituitary and/or ovarian level. The interaction of the gonadal and adrenal axes has not been studied in the diabetic female rat. The purpose of this study is twofold: first, to determine the level of dysfunction in the hypothalamic-pituitary axis caused by diabetes in the adult female rat controlling for stage of the estrous cycle, and, second, to evaluate basal corticosterone secretion in female diabetic rats. Sixty cycling 40 day-old female rats were randomly assigned to 3 groups; control (n = 32), diabetic (n = 14), and diabetic insulin-replaced animals (n = 14). The level of hyperglycemia in each group was documented by glycosylated hemoglobin levels and biweekly blood glucoses. Three weeks after induction of diabetes, pituitary luteinizing hormone (LH) responsiveness following an i.v. injection of gonadotropin-releasing hormone (GnRH) was assessed in representative diestrous rats from each group. All animals were sacrificed in either diestrus or proestrus for determination of GnRH concentration in the hypothalamus, LH and follicle stimulating hormone (FSH) content in pituitary and LH, FSH, estradiol and corticosterone in serum. Uterine weight to body weight ratios (a bioassay for estrogen) were also calculated. Hypothalamic GnRH concentration was significantly lower in diabetic versus control diestrous rats. Basal pituitary and serum gonadotropin levels were not different between any groups. GnRH-stimulated serum LH levels were higher in diabetic vs. control and diabetic insulin-treated animals. LH surges occurred in the control and diabetic insulin-replaced but not the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111888 TI - Terminations of LHRH-immunoreactive fibers in the subfornical organ of the opossum: an ultrastructural study. AB - Electron microscopic immunocytochemical approaches were used to analyze LHRH containing elements in the subfornical organ of the opossum, a species in which this input to the subfornical organ is prominent. Not only were LHRH synaptic specializations easily demonstrated in the subfornical organ, forming axo dendritic and axo-axonal contacts, but also LHRH-immunoreactive fibers contacted astrocytic end-feet on fenestrated capillaries and were found in the subependymal layer. LHRH-carrying elements in the subfornical organ may be important for relating reproductive functions to body fluid balance. PMID- 2111889 TI - Existence of L-dopa immunoreactive neurons in the rat preoptic area and anterior hypothalamus. AB - We demonstrate the presence of L-DOPA (L-3,4-dihydroxyphenylalanine)-labelled cell bodies and fibers in the rat preoptic and anterior hypothalamic areas, using a rabbit polyclonal antiserum against conjugated L-DOPA and a glutaraldehyde coupled immunohistochemical technique. In contrast, using a monoclonal anti conjugated dopamine (DA) antibody, no DA labelled neurons were detectable in the preoptic region, whereas a few weakly immunostained DA neurons began to appear in the ventral part of the medial preoptic area. These observations point to the hypothesis that these cells contain mainly L-DOPA neurons in the preoptic and anterior hypothalamic areas. Thus, we suggest that L-DOPA plays a more important role in the hypothalamic functions than has been hitherto assumed. PMID- 2111890 TI - Comparative immunohistochemical study of the distribution of neuropeptide Y, growth hormone-releasing factor and the carboxyterminus of precursor protein GHRF in the human hypothalamic infundibular area. AB - It is now well documented that various polyclonal antisera to the human growth hormone-releasing factor (hGHRF, somatocrinin) visualize in the brain by immunohistochemistry the classical hypothalamic hypophysiotropic neurons and also antigens present in otherwise characterized peptidergic neuronal systems. The nature of these antigens is still an open question. One of these hGHRF antisera, raised against an immunogen of hGHRF1-44NH2, labels in the arcuate nucleus of the human mediobasal hypothalamus the neuropeptide Y (NPY) containing neurons which for the most part constitute a tuberoextrainfundibular system. The identity of the hGHRF-like substance present in these neurons with true somatocrinin has been assessed by performing a comparative immunohistochemical study including sequential double and triple labeling using the antiserum to hGHRF1-44NH2 in conjunction with antisera to the carboxyterminus of preprosomatocrinin (CTPG) and to NPY. This made it feasible to dissociate the hGHRF1-44NH2-immunoreactive neurons into two major subpopulations costaining either for CTPG of NPY, and a minor neuronal group displaying simultaneously the three labelings. A subset of arcuate neurons also showed NPY staining only. These results suggest that (1) the hGHRF-like antigen present in the majority of the NPY neurons is not true somatocrinin, or alternatively that preprosomatocrinin undergoes a unique maturational processing in these neurons, and (2) a subset of tuberoinfundibular somatocrininergic neurons produces and releases NPY which may be involved in the multifactorial control of the pituitary function. PMID- 2111891 TI - An oxytocin precursor intermediate circulates in the plasma of humans and rhesus monkeys administered estrogen. AB - Estrogen releases into plasma the human oxytocin neurophysin, previously termed the estrogen-stimulated neurophysin. Because oxytocin and its neurophysin are synthesized as part of a common precursor, stimuli which release the hormone should also release neurophysin and vice versa. However, release of oxytocin with its neurophysin has been difficult to demonstrate by immunological assay in humans administered estrogen. Under this condition, the oxytocin immunoreactivity that is released with the oxytocin neurophysin is a novel peptide which is antigenically similar to oxytocin yet is not oxytocin. Co-release of the oxytocin like peptide with oxytocin neurophysin suggested that the oxytocin-like immunoreactivity may be a partially processed form of oxytocin. To test this hypothesis the synthetic oxytocin precursor intermediates oxytocin-glycine (G), oxytocin-glycine-lysine (GK), and oxytocin-glycine-lysine-arginine (GKR), were tested for cross-reactivity with the various oxytocin antisera used in this laboratory to distinguish the oxytocin-like peptide from oxytocin. Oxytocin-G, but not oxytocin-GK or GKR, showed extensive cross-reactivity with the oxytocin antiserum (Ab 1), which is known to detect the oxytocin-like peptide of human plasma. Plasma from men and rhesus monkeys administered estrogen and from pregnant women was separated by HPLC and oxytocin Ab 1 immunoreactivity was eluted from the column with the same retention time as synthetic oxytocin-G. Estrogen releases an oxytocin precursor intermediate into the circulation of humans and monkeys and may exert an important effect upon posttranslational cleavage of the oxytocin prohormone. These observations suggest a heterogeneity in the intraneuronal posttranslational processing of the oxytocin precursor in estrogen-treated versus nonestrogen-treated primates. PMID- 2111892 TI - Changes of prolactin response to dopamine during the rat estrous cycle. AB - The effects of dopamine (DA) on prolactin (PRL) secretion in anterior pituitary tissue from rats selected during various stages of the estrous cycle were analyzed under in vitro conditions. The results were examined in relation to plasma PRL, estradiol and progesterone levels. During the estrous cycle there was a marked variation in the responsiveness of the lactotrophs to the inhibitory action of DA. Rapid changes occurred during proestrus: pituitary lactotrophs were not sensitive to the inhibitory action of 10 nM DA at 15.00 and 17.00 h and were less sensitive to 1 microM DA compared to 09.00 h (p less than 0.01), 12.00 h (p less than 0.05) and 19.00 h (p less than 0.05). This lowest PRL response to DA was associated with the preovulatory PRL surge. The recovery of a higher PRL response at 19.00 h coincided with the decrease of plasma PRL levels. During the remainder of the cycle, plasma PRL levels remained low in estrus, diestrus 1 and diestrus 2. Lactotrophs were sensitive to 1 microM and 10 nM DA during estrus and diestrus 2 but a significant lower PRL response to 1 microM DA (p less than 0.05) and no PRL response to 10 nM DA was observed in diestrus 1. These data show that alterations in the sensitivity of the lactotrophs' responsiveness to DA occur in the anterior pituitary gland during the rat estrous cycle and can lead to the removal of DA inhibition in the presence of physiological DA concentrations. This phenomenon is consistent with the fact that DA could be involved in the preovulatory PRL surge during the estrous cycle. PMID- 2111893 TI - Hypothalamic neuronal activity associated with onset of pseudopregnancy in the rat. AB - The electrical activity of several hypothalamic sites, before and following cervical stimulation, was examined in an attempt to evaluate the central nervous system processes involved in the induction of pseudopregnancy in the rat. Cervical stimulation, resulting in pseudopregnancy, induced a sequence of neuronal changes at: 3.8, 4.4, 11.6, 20.1, 30.8, 44.5, 51.2, 51.7, 62.4, 85.1 and 111.5 min after stimulation in the preoptic area, lateral hypothalamus, ventromedial hypothalamus, preoptic area, suprachiasmatic nucleus, lateral hypothalamus, preoptic area, ventromedial hypothalamus, lateral hypothalamus and anterior hypothalamus, respectively. These results suggest that the preoptic region contains both the facilitatory neuronal mechanism and also an inhibitory system. The latter could tonically inhibit the expression of the nocturnal prolactin surge. We conclude that the sequence of neuronal events observed in various hypothalamic areas is in part responsible for the process which results in pseudopregnancy. PMID- 2111894 TI - Role of androgens in the regulation of sexual behavior in the female musk shrew. AB - These experiments were conducted to determine whether androgens are involved in the regulation of female sexual behavior in the musk shrew (Suncus murinus). In the musk shrew, sexual behavior can be reinstated after ovariectomy by the administration of supraphysiological doses of either estradiol (E2) or testosterone. However, physiological doses of E2 are not effective in this regard. To examine the role of androgens, ovariectomized (OVX) females received testosterone-filled hormone implants. These implants reinstated sexual behavior in a dose-dependent manner. To determine whether the aromatization of androgen is essential for restoration of sexual behavior, the nonaromatizable androgen, dihydrotestosterone (DHT), was administered to OVX females either alone or with an implant containing E2; sexual behavior was not restored. In the third experiment, gonadally intact females, treated with the aromatization inhibitor 1,4,6-androstatriene-3,17-dione (ATD) exhibited no sexual behavior and had significantly lower levels of aromatase activity in the medial basal hypothalamus/preoptic area than control females. In the last experiment, OVX females implanted with testosterone and given concurrent ATD treatment demonstrated significantly less sexual behavior as compared with controls. These results suggest that either estrogens produced via androgen aromatization in the brain and/or an intermediate product in the aromatization process are involved in the regulation of sexual behavior in the female musk shrew. PMID- 2111895 TI - Comparisons of the nuclear uptake of [3H]-testosterone and its metabolites by the brains of male and female macaque fetuses at 122 days of gestation. AB - Testosterone secreted by the testis of the macaque fetus is thought to influence certain aspects of the brain's subsequent development which may be responsible for the ontogeny of sexually dimorphic patterns of behavior. To compare the interactions between testosterone and the receptors for androgens and estrogens in brain cell nuclei in the two sexes, 7 intact female fetuses and 5 intact male fetuses were injected in utero at about 120 days of gestation with [3H] testosterone (250 microCi i.v. or 500 microCi s.c.). One hour later, fetuses were delivered by cesarean section, and samples of brain and peripheral tissues were homogenized and separated into purified nuclear and supernatant fractions. Fractions were analyzed by high performance liquid chromatography to measure levels of [3H]-testosterone and its metabolites. Concentrations of radioactivity extracted from cell nuclei were significantly higher in the hypothalamus-preoptic area than in other brain areas (p less than 0.001); [3H]-estradiol represented 65.0 +/- 5.7% of this radioactivity and nuclear concentrations of this metabolite were 73% lower in males than in females (p less than 0.001). Nuclear concentrations of [3H]-testosterone in the pituitary gland (68.9 +/- 8.8% of extracted radioactivity) were 48% lower in males than in females (p less than 0.001). There was no evidence of a sex difference in the tissue uptake of radioactive steroids from blood, but in males, levels of endogenous plasma testosterone (599.8 +/- 208.2 ng/100 ml) were significantly higher than in females (37.7 +/- 28.5 ng/100 ml; p less than 0.01), and the specific activity of [3H]-testosterone in blood was consequently lower in males than in females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111896 TI - Non-steroidal follicular factors attenuate the self-priming action of gonadotropin-releasing hormone on the pituitary gonadotroph. AB - Pituitary glands of pro-oestrous and oestrous rats were perifused in series with isolated ovarian follicles and the luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotropin-releasing hormone (GnRH) were measured. Pituitary glands from pro-oestrous rats, perifused with the effluent medium from isolated preovulatory follicles, showed a significant reduction in the self-priming effect of GnRH as observed from the typical biphasic LH response to a continuous GnRH challenge. The initial FSH response to GnRH was also reduced. A similar trend was seen in the LH responses of pituitary glands from oestrous rats but results were not significant; there was no parallel reduction in FSH release. It is unlikely that the attenuation of GnRH self-priming was due to the steroids released by the isolated follicles. LH responses of pro-oestrous pituitaries, perifused with medium containing 200 pg oestradiol/ml, 5 ng progesterone/ml or 200 pg testosterone/ml were similar to paired controls as were the responses when all three steroids were added to the perifusing media at identical concentrations. Furthermore, when steroids were charcoal extracted from the effluent medium of perifused isolated follicles the biological activity of this medium in attenuating GnRH self-priming was not destroyed. Finally, the effects of purified bovine inhibin and steroid-free human follicular fluid (hFF) on LH responses were compared. Purified inhibin at a concentration of 20 or 50 ng/ml perifusing medium had no effect on GnRH-stimulated LH release although GnRH stimulated FSH secretion was significantly reduced toward the end of an extended perifusing period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111897 TI - Absence status. PMID- 2111898 TI - Focal resection for malignant partial seizures in infancy. AB - There is little experience with excisional surgery for drug-resistant partial seizures in very young patients. We describe our experience with 5 infants under 1 year of age with malignant partial seizures and deteriorating developmental status. All were experiencing frequent daily seizures that did not respond to 1st line antiepileptic medications at high therapeutic serum levels and considerable medication toxicity. Three infants had complete resection of epileptic tissue (frontal corticectomy and prefrontal lobectomy) and are seizure-free. Two underwent partial resection (lateral temporal lobectomy, frontal corticectomy with anterior callosotomy) and have experienced a significant reduction in seizure frequency. Surgery did not result in any significant neurologic deficit or lead to compromise of developmental status. From these data, we tentatively conclude that excisional surgery can be performed safely in selected infants with medically uncontrolled malignant partial seizures and may significantly improve long-term seizure status. Referral to a tertiary center specializing in early childhood epilepsy surgical evaluation may be considered in these circumstances. PMID- 2111899 TI - A proton magnetic resonance spectroscopy study of focal epilepsy in humans. AB - Localized in vivo proton magnetic resonance spectra obtained from diseased areas in 2 patients with chronic localized encephalitis (Rasmussen's syndrome) showed reduced resonance intensities from N-acetyl compounds, suggesting focally decreased N-acetylaspartate concentrations. One of the patients had epilepsia partialis continua secondary to the encephalitis. In this patient, the spectra demonstrated a high lactate resonance intensity (not seen in the normal, contralateral hemisphere) corresponding to an estimated local concentration of about 7.5 mM. We speculate that the observed decrease in the N-acetyl compound resonance may be a biochemical correlate of the neuronal loss characteristic of this disease. The results establish that excessive accumulation of lactate can occur in the human brain as a result of seizure activity even in the absence of ischemia. Thus, bioenergetic compromise may be 1 predisposing factor to the death of excitable cells in the epileptogenic area. PMID- 2111900 TI - [Prevalence, significance and therapy of premature LH rise and peak in the In Vitro Fertilization program]. AB - The incidence of the premature LH-rise/peak has been analysed in view to the pregnancy rate in 139 HMG and combined Buserelin + HMG cycles of an IVF-ET/GIFT program. A premature LH-rise/peak seems to be correlated with a lower pregnancy rate; therefore the cancellation of the stimulation is recommended in these cases. A gonadotropin suppression by the GnRH-analog Buserelin before and during the HMG treatment proved to be a good method to prevent a premature LH-rise/peak and to decrease the number of cancelled stimulation cycles. PMID- 2111901 TI - [Gene rearrangement in leukemia]. AB - In this report we summarize our experiences based on the gene rearrangement study of 111 leukaemic patients of different kind. The lymphocyte DNA of the patients was studied for rearrangement of the immunoglobulin light chain constant-, the heavy chain joining- and the T cell receptor beta chain constant region. Our data have well supplemented the results of the monoclonal antibody experiments. In 33 cases the DNA study was in good agreement with the immunological data. In 42 our data helped in gave different results, immunological results. In 11 cases evaluating the DNA and immunological data indicating the necessity of further investigation. The results were inconclusive in 25 cases. As a conclusion we consider the gene rearrangement study to be useful for diagnostic purposes. PMID- 2111902 TI - [Pheochromocytoma in Recklinghausen neurofibromatosis]. AB - The authors describe the case of a 38-year-old hypertensive woman who suffered from neurofibromatosis, pheochromocytoma, scoliosis and diabetes mellitus. Because of the residual pheochromocytoma surgical intervention was repeated. According to the available literature this is the first case in Hungary where pheochromocytoma was associated with neurofibromatosis. PMID- 2111903 TI - [Prenatal diagnosis of Hunter's disease]. AB - The authors give a short report about the first-trimester prenatal detection of Hunter's disease (MPS II) inherited as X-linked disorder. There is written about a family having one affected child with Hunter's syndrome. Chorionic villus sample was taken at 10th weeks of gestation in the new pregnancy of the mother. The sex of the fetus was a male determined by DNA analysis. The activity of sulphoiduronate sulphatase was very low. The enzyme activity was also extremely low in the cultured cells from amniotic fluid taken at 16th weeks of gestation. On the basis of these results the pregnancy was terminated at parents's request. The diagnosis of Hunter's disease was confirmed by measuring the enzyme activity of the cultured fibroblasts from the male fetus. PMID- 2111904 TI - [Therapeutic use of a gonadotropin releasing hormone analogue in breast cancer]. AB - Superagonistic analogues of Gn-RH given chronically produce a paradoxic inhibition of pituitary gonadotropin secretion and consequently decrease the peripheric hormones estradiol and progesterone to a postmenopausal level. For curative purposes buserelin (SuprefactR, Hoechst) treatment has been performed by the authors in two cases of breast cancer. The patients--one with NED (no evidence of disease) and the other with pulmonary and osseal metastases--in addition to low hormonal levels developed amenorrhoea. A group of climacteric complaints were observed without any toxic side effects, however. The treatment of premenopausal women suffering from breast cancer with chronic administration of Gn-RH analogues may constitute a valuable alternative to surgical oophorectomy. PMID- 2111905 TI - Protein kinase-c activation inhibits tyrosine phosphorylation of the c-met protein. AB - The mature product of the c-met proto-oncogene is a putative tyrosine kinase receptor of 190 kd with an alpha beta heterodimeric structure. The c-met protein is phosphorylated in vivo on the beta subunit in the gastric carcinoma cell line GTL-16 (Giordano et al., 1988). Western blots with phosphotyrosine antibodies show that tyrosine phosphorylation of the beta subunit is reduced by treatment of GTL-16 cells with protein kinase C activators (tumor promoting phorbol esters such as phorbol 12-myristate 13-acetate, TPA, and beta-phorbol 12,13-dibutyrate, PdBu, or membrane permeable synthetic diacylglycerol 1-oleyl-2-acetyl-sn glycerol, OAG). The inactive analog alpha-phorbol 12,13-didecanoate has no effect. The inhibition induced by TPA is dose dependent and maximal after 1 h. Depletion of protein kinase-C by prolonged treatment with TPA (18-48 h) increases the phosphorylation on tyrosine of the beta subunit. Phospho-amino acid analysis of the c-met protein immunoprecipitated from [32P]orthophosphate-labelled GTL-16 cells shows that protein kinase-C activation leads to an increase in serine phosphorylation and to concomitant decrease in tyrosine phosphorylation. These results suggest that, similar to the EGF and insulin receptor, the putative receptor encoded by the c-met proto-oncogene may be negatively modulated by protein kinase-C phosphorylation. PMID- 2111906 TI - Antibody is responsible for the passive transfer of immunity to mice from rabbits, rats or mice vaccinated with attenuated Schistosoma japonicum cercariae. AB - Sera from rabbits, rats and mice multiply-vaccinated with attenuated cercariae of Schistosoma japonicum conferred high levels of resistance against challenge to naive recipient mice (up to 97, 64 and 60% respectively). Vaccinated rabbit and rat sera were given before challenge and vaccinated mouse serum 5 days after challenge. To show that the protective factors in these sera were antibodies, vaccinated rabbit and mouse sera were fractionated by protein A-Sepharose and the fractions precipitated by 50% ammonium sulphate. The protein A-Sepharose binding or non-binding fractions in vaccinated rabbit serum transferred approximately equal levels of significant resistance to mice, suggesting that both the IgG and non-IgG components of vaccinated rabbit serum are protective. The major part of the protective activity in vaccinated mouse serum was transferred to recipients by the protein A-Sepharose binding fraction, i.e. the IgG antibodies. Heat inactivation of sera at 56 degrees C for 3 h affected the protective capacity of vaccinated rat sera, but not that of vaccinated rabbit or mouse sera. PMID- 2111907 TI - Serotype-specific serum IgG antibodies to lipopolysaccharides of Pseudomonas aeruginosa in cystic fibrosis: correlation to disease, subclass distribution, and experimental protective capacity. AB - Various studies have demonstrated pronounced systemic IgG response to Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF). However, antibody response to serotype-specific lipopolysaccharides (LPS) has never been studied. ELISA for detection of IgG antibodies to LPS of nine PA-serotypes and to toxin A were performed with serum of 78 CF patients. Anti-LPS profiles of antibodies were confirmed by SDS-PAGE and immunoblotting techniques. The most frequent PA serotypes found were immunotypes (IT) IT-1 and IT-2, and Habs-3 and Habs-4. Ten patients without PA colonization showed no detectable antibody titers. In patients with chronic PA colonization (n = 46), these antibody titers were significantly (p less than 0.005) higher than in patients with intermittent PA colonization (n = 22). Mean serum antibody titers to LPS of PA IT-1, IT-2, Habs 3, and Habs-4 correlated with duration of PA colonization and with disease severity. Subclass analysis of anti-LPS antibodies revealed elevated levels for all four IgG subclasses and for IgA1. The IgG antibodies to LPS of PA proved to be protective in a murine burn wound sepsis model. We conclude that anti-LPS antibodies to specific PA serotypes in serum may be a sensitive measure of severity and prognosis of CF. Patients with CF show adequate functional immune response to LPS of PA, and it is possible that vaccination against PA before colonization could induce protective immunity. PMID- 2111908 TI - Antitumor activity in skin of Skh and Sencar mice by two dietary beta-carotene formulations. AB - There is currently a great interest in the protective potential of beta-carotene and other micronutrients against carcinogenesis. We investigated the role of beta carotene in modifying 7,12-dimethylbenz[a]anthracene (DMBA)-initiated, 12-O tetradecanoylphorbol-13-acetate (TPA)-promoted, two-stage skin carcinogenesis. We were interested in comparing the protective effects of two types of dietary beta carotene, a beadlet formulation and crystalline beta-carotene, in two strains of mice (Skh:HR-1 and CR:ORL Sencar). Mice were maintained throughout the study on one of these 3% beta-carotene-fortified diets or on control diets. In Week 11 after the start of the diets, the DMBA/TPA treatment regimen was begun. The resulting skin tumors were counted weekly. In addition, serum and skin levels were monitored for beta-carotene at the time of chemical initiation and at the termination of the study. A decrease in the number of cumulative tumors in the beta-carotene-fed animals compared with the appropriate control groups was observed in both strains of mice. However, statistical evaluation of the data revealed that the decrease was significant only in Skh mice. This phenomenon might be explained by the inherent sensitivity of Sencar mice to the two-stage carcinogenesis treatment regimen. The mechanism of the protective effect found in this study is still not clear. Recent data suggest that a vitamin A pathway is not probable but that a direct 1O2 and/or radical-quenching property of the parent beta-carotene molecule may be involved. This study also demonstrates that two-stage-induced skin tumorigenesis can be modified by both types of beta carotene-fortified diets. PMID- 2111909 TI - Pancreas and islet-cell transplantation. Potential cure for diabetes. AB - In the past two decades, results of whole-organ pancreas transplantation have improved considerably. Patient survival rates of 95% to 100% and graft success rates of more than 70% at 1 year have been reported. After successful transplantation, exogenous insulin can be discontinued and the patient's quality of life improved. In the field of islet-cell transplantation, remarkable progress has been made in isolation techniques. However, the problem of rejection without serious sequelae remains. Immunoisolation of islet cells in microcapsules offers an exciting solution, but research is still in preliminary stages. Early results in large animal models are extremely encouraging. PMID- 2111910 TI - Listeria monocytogenes colonization of broiler chickens. AB - In three trials, a total of 108 broiler chickens were unchallenged or challenged orally with either 10(2) or 10(6) cells of Listeria monocytogenes at 1, 14, or 35 days of age. The birds were kept in separate wire-floored brooders and growout batteries, fed unmedicated broiler-starter rations ad libitum, and killed 7 days postchallenge. The ceca, duodenum, spleen, liver (including gall bladder), and a cloacal swab were sampled from each bird and were analyzed for the presence of L. monocytogenes. In Trial 1, L. monocytogenes was recovered on all sampling days, but most frequently from birds challenged when 1 day old. In Trials 2 and 3, recovery was only from birds challenged at 1 day of age. The L. monocytogenes organism was not recovered from any uninoculated control birds. There was a dose related colonization response (10(6) greater than 10(2]; and more recoveries were obtained from the ceca, spleen, and cloacal swabs than from the duodenum and liver. PMID- 2111911 TI - [Significance of scanty bacterial isolation obtained once in newly diagnosed patients with tuberculosis of the respiratory organs]. PMID- 2111912 TI - [Species category of Mycobacteria isolated from cattle and environmental objects]. AB - The results of testing the slaughtered cattle material and environment objects for the presence of Mycobacteria are presented. During 1984-1988 with a stable excretion of pathogenic Mycobacteria, the quantity of the isolated atypical Mycobacteria tended to increase. In 1984 the atypical Mycobacteria made up 24.1% of the cultures isolated from cattle (pathogenic ones being 75.9%); in 1985, 29.0%; in 1986, 31.4%; in 1987, 46.0% and in 1988, 55.8%. For the above period M. bovis amounted to an average of 98.8% with annual fluctuations between 96.65 and 99.1%. During the last 5 years M. tuberculosis cultures ranged from 0.9 to 3.3% (1.92% on the average). M. avium was isolated from cattle in 22 cases out of 212 samples of the examined material (10.3%). As a result of testing of 2397 samples of the environment objects taken from 34 farms, 391 (16.3%) atypical Mycobacteria were isolated. It is necessary to continue, with regard to environmental conditions, the study of animal responses and atypical Mycobacterium carriage in different areas of the country. PMID- 2111913 TI - [Production and characteristics of monoclonal antibodies reacting with human-type M. tuberculosis]. AB - Monoclonal antibodies to M. tuberculosis were produced by hybrid technology. They were described via enzyme immunoassay and immunoblotting. It was shown that these antibodies should be included into IgG class. Besides, they are oriented towards and antigen with a molecular weight of 20 kDa, react with H37Rv at a concentration of 12 ng/ml and with BCG at a concentration of 50 micrograms/ml and fail to react with M. Intracellulare, M. Scrofulaceum and E. coli. PMID- 2111914 TI - Similar behavioral and biochemical effects of long-term haloperidol and caerulein treatment in albino mice. AB - Behavioral and biochemical experiments on male albino mice have revealed similar effects after the cessation of repeated (15 days) haloperidol (0.5 mg/kg daily IP) and caerulein (0.1 mg/kg daily SC) treatment. Tolerance developed to the action of muscimol (a GABA-A agonist, 1 mg/kg IP), caerulein (a CCK-8 agonist, 15 micrograms/kg SC) and flumazenil (a benzodiazepine antagonist, 10 mg/kg IP). Muscimol and caerulein were not able to suppress the motor activity of mice after 15 days treatment with haloperidol and caerulein. Flumazenil, which increased motor activity in saline-treated animals, also failed to affect activity after extended haloperidol or caerulein treatment. In contrast, the motor excitation induced by amphetamine (an indirect dopamine agonist, 3 mg/kg IP) was increased after haloperidol or caerulein administration. In radioligand binding studies the density of dopamine-2-receptors in striatum, opioid receptors in mesolimbic structures, and benzodiazepine and GABA-A receptors in brainstem was significantly elevated after long-term haloperidol or caerulein treatment. Simultaneously, the number of CCK-8, benzodiazepine and GABA-A receptors in cerebral cortex was decreased. It is probable that CCK-8-ergic mechanisms are involved closely in the action of repeated haloperidol treatment. CCK-8 seems to modulate the action of haloperidol through altering the sensitivity of dopamine, opioid, GABA-A and benzodiazepine receptors. PMID- 2111915 TI - Effects of two benzodiazepine inverse agonists, RO 15-4513 and FG 7142, on recovery from pentobarbital and halothane anesthesia in the rat. AB - A new class of drugs, the benzodiazepine inverse agonists, have recently been shown to antagonize some of the behavioral and sedative effects of benzodiazepines, barbiturates, and alcohol. Preliminary studies suggested that at least one of these drugs, RO 15-4513, may also be able to reverse the general anesthetic properties of volatile halogenated agents. Another inverse agonist, FG 7142, exhibits a similar ability to antagonize alcohol or benzodiazepines. However, FG 7142 is less potent than RO 15-4513 and has less affinity for the benzodiazepine receptor (BZR). The present studies were therefore undertaken to compare the analeptic effects and relative potencies of RO 15-4513 and FG 7142 on the anesthetic properties of pentobarbital compared with the general anesthetic agent halothane as measured by the time for recovery of the righting reflex in the rat. Three basic experimental paradigms were employed. Drug (FG or RO) or carrier was administered 5 minutes prior to the induction of pentobarbital anesthesia. Drug or carrier was administered to anesthetized animals 60 minutes after pentobarbital injection. Lastly, drug or carrier was administered 5 minutes prior to 15 minutes of halothane anesthesia. In addition, the selective benzodiazepine antagonist, flumazenil (RO 15-1788), was used to determine if the effects of the benzodiazepine inverse agonists on recovery from barbiturate or halothane anesthesia were due to activity at the BZR. The results revealed that RO was both more potent and more effective than FG at speeding recovery from barbiturate anesthesia in the rat. RO's effects appeared to be primarily due to BZR inverse agonist activity since it could be reversed by the BZR antagonist, flumazenil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2111916 TI - HMG CoA reductase inhibitors in the treatment of hypercholesterolaemias. PMID- 2111917 TI - HMG CoA reductase inhibitors as lipid-lowering agents: five years experience with lovastatin and an appraisal of simvastatin and pravastatin. AB - The HMG CoA reductase inhibitors are the most effective drugs for treating hypercholesterolaemia currently available. They inhibit cholesterol synthesis and thus stimulate receptor-mediated uptake and degradation of low-density lipoprotein cholesterol by the liver. In 30 patients with severe hypercholesterolaemia administration of lovastatin alone or in combination with other lipid-lowering manoeuvres maintained reductions of 25 to 31 per cent in serum cholesterol over five years. The drug was easy to take and well tolerated, the only significant side effect being a reversible myopathy. Two similar compounds, simvastatin and pravastatin, exert comparable effects on serum lipids, including modest reductions in triglycerides and increases in high-density lipoprotein cholesterol. The use of these drugs seems likely to exert a beneficial effect on atherosclerosis. PMID- 2111918 TI - Long-term treatment of acromegaly with a long-acting analogue of somatostatin, octreotide. AB - We have treated 16 acromegalic patients for up to 44 months with octreotide in varying doses. Growth hormone levels were suppressed in 14 patients with associated clinical improvement. IGF-1 levels were measured in 12 and fell into the normal range in 10. Prolactin was suppressed in six hyperprolactinaemic patients but was unaltered in normoprolactinaemic acromegalic patients. Post prandial hyperglycaemia with impaired insulin secretion was noted in all patients, and one patient required oral hypoglycaemic agents. Octreotide did not affect thyroid function. CT scans from before and after six months of treatment demonstrated minimal tumour shrinkage in only two patients. Octreotide was well tolerated with no serious haematological or biochemical disturbance and no evidence of malabsorption. Two patients developed gallstones. Octreotide is effective in acromegaly. The development of gallstones is the only serious adverse event we have encountered. PMID- 2111920 TI - Controlling tuberculosis: the pathologist's point of view. PMID- 2111919 TI - Candidates for the mouse Fc alpha R: beta-galactosyl transferase, secretory component and a 38-kDa protein. PMID- 2111921 TI - The spectrum of tuberculosis and leprosy: what can be the significance of specific humoral responses? PMID- 2111922 TI - In vivo vs. in vitro killing of virulent Mycobacterium tuberculosis. PMID- 2111923 TI - Killing intracellular mycobacteria in in vitro macrophage systems: what may be the role of known host microbicidal mechanisms? PMID- 2111924 TI - Intracellular killing of mycobacteria. PMID- 2111925 TI - Sources of variability in assays of the interaction of mycobacteria with mononuclear phagocytes: of mice and men. PMID- 2111926 TI - Antimycobacterial functions in bone-marrow-derived macrophages. PMID- 2111927 TI - A 25-kDa fraction from Mycobacterium tuberculosis that inhibits leukocyte bactericidal activity: reversal by gamma interferon and clofazimine. PMID- 2111928 TI - The role of activated macrophages in protection and immunopathology in tuberculosis. PMID- 2111929 TI - Mycobacteria and macrophage activation. AB - Recent studies that challenged some older concepts have led to the following conclusions: 1) During an infection of mice with M. bovis, BCG macrophages are activated according to certain criteria, but the increase in their bactericidal or bacteriostatic activity is limited to a small number of bacteria species; 2) interferon-gamma can activate macrophages in vitro and in vivo, but these cells do not exhibit increased bactericidal activity; 3) a 65-kDa protein of mycobacteria can activate macrophages in vivo to a limited degree only; and 4) granulocytes stimulated with interferon-gamma kill ingested M. fortuitum more efficiently than normal granulocytes. PMID- 2111931 TI - Efficient use of endpoints in clinical trials: a clinical perspective. AB - Efficiencies in the use of endpoints in clinical trials are hard won, not easy. They depend upon the shifting of study resources among clinical centres and central units, as well as between numbers of participants and the costs of the endpoint measurement. Costs of endpoint measurement and evaluation do not tell the whole story; nor do costs multiplied by the total number of patients to be recruited; other costs generated by a particular endpoint must also be taken into account. Each clinical trial must be considered separately for the efficient use of endpoints. PMID- 2111930 TI - Pathophysiological mechanisms of HIV-induced defects in haematopoiesis: pathology of the bone marrow. AB - Bone marrow biopsies of 96 HIV1-infected patients were analysed histologically and by immuno- and enzyme histochemical techniques. Independently of the stage of disease, the bone marrow frequently exhibits hypercellularity and features of dysplastic haemopoiesis combined with mesenchymal alterations. In situ immunohistochemical analysis shows that there is a marked reduction in expression of the proliferation-associated nuclear antigen recognized by the Ki67 antibody. Comparison with non-infected controls reveals that there is a reduction in CD34+/myeloperoxidase-/naphthol AS-D chloroacetate- progenitor cells and an overproportional decrease in CD8+ lymphocytes in the bone marrow. Double staining revealed the presence of gag-coded HIV1 proteins in the above-mentioned CD34+ progenitor cells, in myelopoiesis cells, megakaryocytes and above all, in CD68+/acid phosphatase+ and alkaline phosphatase+ bone marrow reticular cells. From the latter results, it was concluded that HIV1-infected reticular cells may be disturbed in their ability to produce factors responsible for the short-range regulation of haemopoietic activity. PMID- 2111932 TI - Using cost-effectiveness analysis to improve the efficiency of allocating funds to clinical trials. AB - This study applied a cost-effectiveness model to seven randomized trials. The model demonstrates the effect of design choices made in the planning stages of a clinical trial on the costs and benefits derived from conducting the trial. The study focused on one parameter used to calculate sample size: the minimum clinically important difference in event rates between control and experimental therapies. The study shows that the model can be operationalized to these trials. A computerized software package and manual has been developed to simplify the calculations. While there was some variation in the incremental cost effectiveness ratios across the seven trials in this study, all ratios may be below the funding threshold. This analytical technique can be used to demonstrate explicitly the resource consequences of the design of randomized trials and perhaps to set funding priorities. PMID- 2111933 TI - Sickle cell anaemia trial. AB - The major cause of death in sickle cell anaemia is from infection, especially infection caused by Streptococcus pneumoniae. Meningitis, pneumonia and septicaemia caused by this organism are the primary types of infection leading to death. Children under three years of age are at highest risk. We have known for over twenty years that approximately 30 per cent of the infants born with sickle cell anaemia will become infected in the first three years of life and one-third can be expected to die from the infection. These data were the reason that we conducted the Prophylactic Penicillin Study (PROPS), a trial to investigate the effectiveness of oral prophylactic penicillin in preventing severe infection due to S. pneumoniae. This investigation was a very efficient, cost effective study because of its timeliness and its conduct within the framework of an ongoing study. Moreover, the question being answered was simple and focused with up-to date data that permitted accurate estimates of sample size and incidence. PMID- 2111934 TI - Anesthetic management of laser airway surgery. AB - This brief review of the anesthesiologist's role in the team effort necessary for the safe treatment of airway tumors by laser beam is provided to acquaint the referring physician or medical oncologist with some of the anesthesiologist's operating room concerns and how they are met. The necessity of bringing the patient to a level of maximum physiologic reserve prior to treatment becomes obvious with information gained by scanning this review. The referring physician or medical oncologist aids the patient and the anesthesiologist and surgeon by performing a thorough preoperative cardiopulmonary evaluation and therapeutic intervention, as indicated by patient need. The review includes a description of the actions of the carbon dioxide (CO2) and neodynium-yttrium aluminum garnet (YAG) lasers, "laser safety" for patients and personnel, monitoring, guarding the airway, ignition dangers, and comments on the use of jet and high frequency jet ventilation (HFJV). PMID- 2111935 TI - [Ergotism: an occasional unrecognized cause of acute ischemia of the extremities]. AB - Vasospasm related to ergot intoxication has been recognised since the Middle Ages when it occurred due to ingestion of rye contaminated with Claviceps purpurea. Today ergotism is a rare cause of peripheral ischaemia, most often associated with ergotamine tartrate therapy for migraine headaches. Recognition of the typical angiographic pattern is important, as the classic drug history may not be obtained, and the cause of the ischaemia can be overlooked. Early diagnosis is important as the outcome may be serious if left untreated. Arterial vasospasm, collateralisation, and secondary thrombus formation are the major angiographic findings. Ergotism responds to conservative therapy which includes drug withdrawal, intravenous nitroprusside, fluid therapy and heparinisation. We describe the angiographic findings of four cases and report on the results of therapy. PMID- 2111936 TI - Lipoprotein heterogeneity and its effect on apolipoprotein assays. AB - A number of techniques have been proposed for separating lipoproteins according to their physicochemical properties. However, more recent evidence has pointed out that the physicochemically defined lipoproteins such as VLDL, IDL, LDL or HDL are both chemically and metabolically heterogeneous. According to Alaupovic concept, the plasma lipoprotein system consists of a mixture of particles, each of which is characterized by unique apolipoprotein composition. Using enzyme linked differential antibody immunosorbent assay and differential electroimmunoassay, we have discovered that the determination of lipoprotein particle profiles is essential for further clarification of the diagnostic value of measuring apo B and apo A-I. The metabolism of apo B and apo A-I containing lipoprotein particles seems to be affected primarily by their corresponding apolipoprotein composition. Some particular subpopulations of apo B containing lipoprotein particles, such as LpB containing only apo B, LpB:E containing apo B and (a), have been identified as important risk factors for atherosclerosis. We have also recently demonstrated that the protective effect of HDL is due to particles containing apo A-I but not apo A-II (LpA-I), while those containing apo A-I and apo A-II (LpA-I:A-II) have little or no effect. Dyslipoproteinemias are characterized by distinct profiles of apo B containing particles. Abnormalities in apo A-I containing particles distribution are related to the family history of coronary artery disease in young children and could explain differences in age standardized mortality from ischaemic heart diseases in different populations. Moreover hypolipidemic drugs seem to affect discrete apo B and apo A-I particles in a specific manner. PMID- 2111937 TI - Apolipoprotein assays: standardization and quality control. AB - A correct approach to standardization, accuracy-based methods, and well-defined quality assurance programs is indispensable for the definition of international reference intervals of apo A-I and apo B. Variability in the immunochemical determination of apo A-I and apo B can be due to both preanalytical and analytical variations, and standardized laboratories should evaluate and minimize each source of error in determining the reference intervals. A key requirement to reduce the variation between measurement techniques is the use of a common protocol for the calibration of the different methods. The basis of a calibration system is the primary standard with the absolute mass accurately determined. The primary standard is indispensable in assigning an accurate target value to reference materials with a reference method in which the primary standard immunochemically reacts the same as the protein in plasma. The reference material, which must behave immunochemically the same as the patient's sample in all methods, is then used to assign a target value to the calibrator in each method and system. Following this procedure, all assay results can be traced back to the primary standard via the serum reference material. The development and distribution of reference and quality control materials, which do not exhibit matrix effects between methods, is fundamental for the standardization process. PMID- 2111938 TI - Standardization of commercial assays for serum Apo A-I and Apo B: a consensus procedure for the calibration of reference materials. AB - Commercial apolipoprotein A-I and B assays show a broad variation of results. This is particularly evident for the different Apo B test kits available commercially. The cause of these differences is mainly due to the inadequate international standardization of apolipoprotein assays. A common effort is at present made by commercial organizations within the International Federation of Clinical Chemistry together with the IFCC Committee on Apolipoproteins to achieve a consensus on a practical standardization procedure for apolipoprotein measurements. The aim is to calibrate all commercially available Apo A-I and Apo B test kits using frozen serum pools (at three levels) previously standardized against primary reference materials. Secondary serum reference materials (at three different concentrations) (SSRM) will be selected among those offered by industrial organizations to serve as "International Master Calibrators". These will replace the Interim Serum Reference Materials (frozen serum pools) which cannot be delivered indefinitely. The secondary serum reference materials will be used by all commercial organizations to control the validity of their own calibrations. PMID- 2111939 TI - A comparative study on the effects of rIL-4, rIL-2, rIFN-gamma, and rTNF-alpha on specific T-cell non-responsiveness to mycobacterial antigens in lepromatous leprosy patients in vitro. AB - We have studied lepromatous leprosy (LL) as a human model disease for T-cell non responsiveness to specific mycobacterial antigens and studied the effect of rIL 4, rIL-2, rIFN-gamma and rTNF-alpha thereon. T-cell non-responsiveness to Mycobacterium bovis bacillus Calmette-Guerin (BCG) or purified protein derivative of M. tuberculosis (PPD) antigens could be overcome in 5 out of 8 non-responder patients by rIL-2 and in 2 out of 8 by rIL-4. The ability of rIL-4 to overcome BCG/PPD non-responsiveness was strongly dose-dependent. When rIL-2 and rIL-4 were added simultaneously, they seemed to synergize in their effect. T-cell non responsiveness to M. leprae could be overcome only in 2 out of 18 non-responders by rIL-2 but not by rIL-4 alone. The ability of rIL-2 to overcome T-cell non responsiveness to M. leprae antigens became particularly marked when the recombinant 65-kDa heat shock antigen of M. leprae was used instead of whole bacilli. Exogenously added rIL-4, and to a lesser extent rIL-2, strongly enhanced existing T-cell responses to BCG or M. leprae in the majority (8 out of 11) of responders. These findings may have implications for the in vivo manipulation of the immune response by recombinant lymphokines and vaccines. PMID- 2111940 TI - Results of the treatment of cardiac arrhythmias with Palpitin. AB - 1) Palpitin has distinguishable antiarrhythmic effect in different type of cardiac arrhythmias of both supraventricular and ventricular origin, and of various ethiopathogeneses. 2) Antiarrhythmic effect is observed in most patients, already 24 hours after initiation of treatment. 3) Untoward effects, although occurring relatively frequently, usually do not cause such severe alterations which lead to a discontinuance of therapy. 4) Palpitin may be used in long-term treatment of outpatients. PMID- 2111941 TI - Susceptibility of South African Bulinus africanus populations to infection with Schistosoma haematobium. AB - The use of intermediate host snails of Schistosoma spp. which are insusceptible to infection has been proposed as a possible method of controlling schistosomiasis. The objective of this approach is to change the susceptibility of natural snail populations from being predominantly susceptible to a non susceptible state, through the release of refractory snails into natural habitats. In an attempt to determine whether or not such refractory Bulinus africanus populations occur in eastern South Africa, F1 generation snails of populations from 8 different areas were exposed to miracidia hatched from eggs excreted in the urine of schoolchildren infected with Schistosoma haematobium in the Nelspruit district. The proportion of snails successfully infected ranged from 27 to 100%, which revealed considerable genetic heterogeneity amongst populations of the same snail species. One population from Natal could be regarded as partially refractory, while a laboratory population from Durban proved to be 100% susceptible. A completely refractory strain of B. africanus has not yet been identified. PMID- 2111942 TI - Penicillinase-producing Neisseria gonorrhoeae in Ndola, Zambia. PMID- 2111943 TI - Antibodies to Plasmodium falciparum sporozoites following a malarial outbreak in a non-endemic area of Sri Lanka. AB - An enzyme-linked immunosorbent assay (ELISA) based on the synthetic peptide (NANP)40 was used to characterize the sporozoite antibodies in an unusual Plasmodium falciparum outbreak in a non-malarious area in Sri Lanka. A positive antibody response was seen in 62% of patients with their first P. falciparum illness. There was no correlation between sporozoite antibodies and the antibody against blood stages, determined by immunofluorescence assay. The majority (91%) of the patients lost the antibodies to circumsporozoite (CS) protein within one year (in the absence of re-exposure). Three patients had high levels of CS antibodies even after one year, and this persistence was related to the level of the initial antibody response. In the area of the outbreak 10% of schoolchildren had antibodies to the (NANP)40 peptide. 21% of the 42 children with present or past overt malaria were antibody positive. Of the children with no such background, 8% were antibody positive. The corresponding seropositivity rates for asexual blood stages were 31% and 1% for the 2 groups respectively. It is concluded that (NANP)40 ELISA is potentially a valuable tool in sero epidemiology, particularly in situations of seasonal transmission and recurrences due to drug resistance. PMID- 2111944 TI - Transmission of Chagas disease through renal transplantation: report of a case. PMID- 2111945 TI - Cryopreservation of Cryptosporidium sp. oocysts. PMID- 2111946 TI - Sonographic studies of schoolchildren in a village endemic for Schistosoma mansoni. AB - Parasitological, clinical, and sonographic examinations were performed on 309 school children in a village endemic for schistosomiasis mansoni. Data from the 255 denying treatment within the previous 2 years were analysed separately. On a single Kato examination 42% were uninfected; the remainder had light (26%), moderate (21%), or heavy (11%) infections with Schistosoma mansoni. Hepatomegaly (53%) and palpable spleens (35%) were common but clinical and parasitological findings often were unrelated. Abdominal sonography also demonstrated a high frequency of hepatomegaly (82%) and splenomegaly (49%). Sonographically determined liver span and spleen size correlated with the egg count. Sonographic lesions of periportal fibrosis of schistosomiasis mansoni with thickening of portal tracts and portal vein walls were frequently present and more common in infected than in uninfected children, and were correlated with the number of S. mansoni ova in the stool. Ultrasonographically detected periportal fibrosis was a reliable measurement of the prevalence and morbidity of schistosomiasis mansoni in this population, and provided very useful information, even when the parasitological and clinical findings were equivocal. PMID- 2111947 TI - Repeated mass treatment of schistosomiasis mansoni: experience in hyperendemic areas of Brazil. 3. Techniques for assessment and surveillance. AB - Severe morbidity due to schistosomiasis mansoni is now quite rare in Brazil; thus it is proposed that surveillance plus selective and multidisciplinary intervention limited to areas at high risk be the next step. Such a policy has to be carried out periodically and on a state-wide scale, and therefore will have to rely upon cheap and time-saving sampling procedures. Clinical features cannot at present be used as indicators, with the exception of grossly enlarged livers, which are more frequent in areas at high risk. Overall prevalence rates for a county or even city may also be misleading, even if broken down into units of smaller size. Thus, egg counts in the young age groups remain the best indicators for the detection of areas at high risk (i.e., the main foci of transmission). Egg counts performed on pooled specimens adequately reflect the risk rating of a particular neighbourhood, and have a favourable cost-benefit ratio. In addition, it is suggested that field personnel be trained in the empirical recognition of potential foci; such 'screening by suspicion' has been tested and found to be reliable. PMID- 2111948 TI - Schistosome migration in primates: a study in the olive baboon (Papio anubis). AB - The migration of isotopically labelled schistosomula of Schistosoma mansoni from the skin to the hepatic portal system of baboons was tracked by autoradiography of compressed organ preparations. Passage of schistosomula from skin to lungs was rapid between days 2 and 5, 72% of applied parasites being detected in the lungs at the latter time. There was an equally rapid migration from lungs to liver, 60% of the adult worm burden having arrived by day 9. Perfusion data indicated a final maturation of not less than 78%. No evidence was found to support or refute a systemic phase of migration. Thus, in comparison to rodents, schistosome migration in baboons appears to be faster and more successful, possibly because the lungs do not represent a significant obstacle to migration. PMID- 2111949 TI - Ultrasound scanning for detecting morbidity due to Schistosoma haematobium and its resolution following treatment with different doses of praziquantel. AB - A study to assess the resolution of urinary tract morbidity due to Schistosoma haematobium was conducted on 2 cohorts of schoolchildren attending neighbouring schools in Kilombero District, southern Tanzania. Schoolchildren were screened for S. haematobium infection using the standard World Health Organization filtration technique and subsequently examined for urinary tract pathology using a portable 3.0 MHz sector scanner (Siemens Sonoline 1300). Treatment with praziquantel was given to all infected children. Children with observed urinary tract pathology received either 20 (n = 52) or 40 (n = 79) mg/kg body weight and were sonographically re-examined one, 2, 3 and 6 months following treatment. Geometric mean outputs of 21 and 19 eggs/ml of urine were detected in the 2 cohorts before treatment. Urinary tract pathology correlated positively with egg output (chi 2, P = 0.02) and microhaematuria (P = 0.0001). Bladder (wall irregularities and polyps) and kidney (congestive changes) pathologies were found in 81% and 36%, respectively, of the group that received 20 mg/kg of praziquantel, and in 78% and 46% of the group that received 40 mg/kg. Six months after treatment, 90.4% and 88.0% parasitological cure rates were obtained using 20 or 40 mg praziquantel/kg body weight. The respective pathology clearances were 88% and 91%. 20 mg/kg of praziquantel was as effective with regard to cure rates and reversibility of morbidity as 40 mg/kg. PMID- 2111950 TI - Immunization of baboons with attenuated schistosomula of Schistosoma haematobium: levels of protection induced by immunization with larvae irradiated with 20 and 60 krad. AB - We have shown previously that baboons (Papio anubis) develop high levels (greater than 80%) of protection against challenge infection following immunization with Schistosoma haematobium cercariae irradiated with 20 krad. In the present study baboons were immunized with schistosomula irradiated with either 20 krad or 60 krad, with variations in the timing and number of larvae comprising each vaccination. Baboons immunized 2 or 3 times with schistosomula irradiated with 20 krad were significantly more protected (85-90%) against challenge infection than baboons similarly immunized with larvae receiving 60 krad (56-50% protection). Baboons immunized with schistosomula irradiated with 20 krad were better protected against challenge infection at 8 weeks after immunization than at 28 weeks after immunization. Protection was manifest by a reduction in worm numbers, tissue and excreta egg counts, gross pathology and, to a lesser extent, by stability of body weight and haematological indices following challenge. Enzyme linked immunosorbent assay (ELISA) results of selected baboon sera showed few differences related to irradiation dose alone, but titres were higher in baboons receiving booster immunizations, and there was a significant correlation between titres immediately preceding challenge and the degree of resistance. Examination of responses to individual schistosomular surface antigens by immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed no correlation between the pattern of antigens recognized and resistance status. As with the ELISA assay, an anamnestic response was detected after vaccination, while the amount of antibody present declined markedly with increasing time after individual immunizations. PMID- 2111951 TI - A simple technique for preparation of bone marrow or peripheral blood buffy coat cells for electron microscopy. AB - A simple and rapid method of processing ethylene-diamine-tetra-acetic acid anticoagulated peripheral blood or aspirated bone marrow for electron microscopy is described. The resultant buffy coat pellet is easily processed into epoxy resin. Semithin sections (1 mu) stained with 1% toluidine blue reveal the various stratified cell layers allowing convenient selection for ultramicrotomy and ultrastructural evaluation. PMID- 2111952 TI - [The surgical treatment of acromioclavicular joint separation with a resorbable PDS cord]. AB - Osteosynthetic complications in surgery of acromioclavicular separations are common. Also, one more intervention is necessary for removing the metallic implants. Use of self-resorbing materials resolves such disadvantages. One more indirect surgical method is presented. After reposition of dislocated acromioclavicular joint and suture of the disrupted ligaments clavicula is fixed to the coracoid processus by a cord of polydioxanone (= PDS). Early postoperative mobilisation without risks is possible in cooperative patients. Self-resorbing implants don't modify the well known indications of conservative and operative treatment. PMID- 2111953 TI - Cutaneous mast cell tumor in a great horned owl (Bubo virginianus). PMID- 2111954 TI - Plasma vitamins A and E and hydrogen peroxide-induced in vitro erythrocyte haemolysis in common marmosets (Callithrix jacchus). AB - Plasma total lipid, cholesterol, all-trans retinol (vitamin A) and alpha tocopherol (vitamin E) concentrations, and the susceptibility of erythrocytes to hydrogen peroxide-induced haemolysis in vitro were investigated in healthy laboratory-bred common marmosets (Callithrix jacchus). The concentrations of alpha-tocopherol and total cholesterol were similar to those of control human subjects. The mean lipid concentration was higher (P less than 0.025) and the retinol concentration lower (P less than 0.001) in the marmosets. The susceptibility of the erythrocytes of the marmosets to hydrogen peroxide-induced haemolysis was high, both in absolute value and relative to the controls. Changes in phospholipid and fatty acid composition might have rendered the red cells susceptible to oxidative stress. PMID- 2111955 TI - Atypical Pasteurella strains producing a toxin similar to the dermonecrotic toxin of Pasteurella multocida subspecies multocida. AB - This paper is the first report of the production of a dermonecrotic toxin by pasteurella strains that do not belong to the species Pasteurella multocida subspecies multocida. Four strains, isolated from cattle with atrophic rhinitis, were characterised phenotypically. The strains were related to pasteurellaceae, but their taxonomic position remained unclear. The strains produced a toxin that caused a haemorrhagic dermonecrosis in guinea pigs and was lethal to mice. Both effects were neutralised by an antiserum against the purified dermonecrotic toxin of P multocida subspecies multocida. Western blot analysis of culture filtrates of the bovine strains revealed a protein, with the same molecular weight as dermonecrotic toxin, which reacted with both polyclonal and monoclonal antibodies against the toxin. In an immunodiffusion test, anti-dermonecrotic toxin serum did not discriminate between the toxin of the bovine strains and the toxin of P multocida subspecies multocida. It is concluded that these atypical pasteurella strains produce a toxin that is closely related to the dermonecrotic toxin of P multocida subspecies multocida. PMID- 2111956 TI - Mutational analysis of the HIV nef protein. AB - The nef protein is one of the regulatory proteins encoded by the human immunodeficiency virus (HIV). It has been shown to down-regulate viral transcription and displays features typical of some membrane-associated G proteins. To define the amino acid sequences involved in several of the properties of the nef protein, the corresponding gene has been submitted to a series of site-directed mutations. The mutants have been evaluated using various parameters which seem to correlate with the biological properties of nef. As previously observed for some signal transducing proteins, membrane localization and correct folding are critical for nef activity. Additionally, two domains, putative "P and G sites" which may be involved in nucleotide binding, have been identified. PMID- 2111957 TI - Expression and characterization of a functional human immunodeficiency virus envelope glycoprotein in insect cells. AB - Recombinant baculoviruses were used to express the gp160 envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) and a truncated variant designated gp160(t) which lacks a transmembrane domain. Glycosylation, proteolytic cleavage, secretion, and biological activities of gp160 and gp160(t) 160(t) were studied in Spodoptera frugiperda cells. Both proteins were rapidly glycosylated and initially were found to be totally endo-beta-N-acetyl-D glucosaminidase H (endo-H) sensitive. However, partial resistance to endo-H was gradually acquired by both molecules. gp160 was found to remain cell-associated, whereas gp160(t) was secreted into the culture medium in large amounts. A fraction of gp160 and gp160(t) appeared to be proteolytically cleaved, and a cleavage product corresponding in size to gp120 was identified in the culture medium. gp160(t) was found to interact specifically with CD4 receptors without any requirement for proteolytic cleavage. The gp160 protein was shown to be expressed on the surface of S. frugiperda cells by direct immunofluorescence. These surface molecules were biologically active, as demonstrated by their ability to induce syncytium formation when cocultivated with HeLa T4 cells. PMID- 2111958 TI - Deletion in a recombinant retroviral vector resulting from a cryptic splice donor signal in the Moloney leukemia virus envelope gene. AB - Proviral DNA derived from a recombinant retroviral vector (LHMlPL), constructed to transduce the human purine nucleoside phosphorylase coding region along with the mouse metallothionein l promoter, was molecularly cloned in order to characterize a deletion previously observed in this provirus. Nucleotide sequence comparison with the original retroviral vector construct revealed two deletions in the cloned provirus. One of the deleted regions originated entirely from within the mouse metallothionein promoter. A second deletion eliminated portions of both viral and metallothionein promoter sequences. All four deletion junctions in the original construct included sequences which conform to those proposed as eukaryotic consensus splice donor and acceptor signals, including a previously unreported cryptic splice donor signal in the Moloney leukemia virus envelope gene. It is concluded that RNA splicing between inadvertently juxtaposed donor and acceptor signals was responsible for the observed deletions. PMID- 2111959 TI - [Tumor necrosis factor and lymphotoxin: endogenous antineoplastic mediators]. PMID- 2111960 TI - The effect of sodium cromoglycate on the induction of experimental IgA nephropathy. AB - Mesangial IgA nephropathy was experimentally induced in ddY mice by oral and parenteral administration of the poliomyelitis vaccine (POLIO), and we then tried to investigate if IgA deposition could be prevented by the concurrent use of sodium cromoglycate (SCG), which is known to inhibit the local mucosal immune reaction. Mucosal and systemic immunity could be induced by the administration of POLIO; proteinuria, increased serum IgA levels, mesangial cell proliferation, mesangial matrix widening, mesangial deposits of IgA, and large electron dense deposits in the mesangium were observed. Concurrent administration of SCG and POLIO resulted in a significant decrease in the serum IgA level and mesangial IgA deposits. The later addition or abstinence of SCG after the 70th day did not influence the glomerular mesangial IgA deposition. But the serum IgA level was still decreased by the continuous treatment of SCG even after the 70th day. Thus, mesangial IgA nephropathy simulating IgA nephropathy in humans could be induced in ddY mice using POLIO and its induction could largely be prevented by the concurrent use of SCG. However mesangial IgA deposits already present could not be cleared by the late administration of SCG. PMID- 2111961 TI - [Jejunal diverticulum. A rare cause of massive intestinal hemorrhage]. PMID- 2111962 TI - The effect of interferon-gamma intramammary administration on mammary phagocyte function. AB - The effect of recombinant bovine interferon-gamma on intramammary phagocyte function of mammary gland was studied in 4 Holstein cows (Study 1) and 7 Holstein cows (Study 2). Recombinant bovine interferon-gamma was intramammarily infused on day 6 of the dry period and phagocytes were collected from lacteal secretions and tested in vitro 24 hours later. Results from Study 1 indicate that phagocytosis of Escherichia coli and Staphylococcus aureus was significantly increased after than before interferon treatment. Similarly, the number of bacteria killed/active phagocyte was enhanced by treatment. Results from Study 2 suggested a trend towards increased production of oxygen dependent bactericidal components and increased killing ability by phagocytes exposed to interferon as compared to control phagocytes. These results from both studies suggest that intramammary infusions of bovine interferon-gamma can stimulate phagocyte function during the early phase of the dry period. PMID- 2111963 TI - Effects of introducing an office chemistry machine. AB - An office chemistry machine was placed into service at the SIU Springfield Family Practice Center. After one year's use of the machine, a study was performed to learn whether there were changes in the methods, of costs, and of care for hypertensive patients compared to the year before introduction of the machine. After introduction of the machine, the physicians began to order individual tests performed in the office rather than chemistry panels performed by the reference laboratory. There was no change in the frequency or costs of testing. Frequency of visits for hypertension and visits for all other reasons did not differ. The level of blood pressure control was the same before and after introduction of the machine. Thus, in this study, introduction of an office chemistry machine resulted in greater revenues to the clinic without changing quality of care or increasing the overall cost of treatment. PMID- 2111964 TI - [Effect of Schistosoma mansoni infection on the immune reactions against heterologous antigens in mice]. AB - Mice (BALB/c or ICR) were infected with Schistosoma mansoni cercariae. After different intervals (mostly eight weeks) the following antigens were injected: a) sheep erythrocytes--b) DNP-thyroglobulin. Afterwards the immune response against these antigens were checked by means of different methods (plaque assay, haemagglutination test, rosette technique). Immune responses to these antigens were depressed in all cases compared to age matched uninfected mice but it was not possible to transfer this immunosuppression with spleen cells to normal or to irradiated recipients. PMID- 2111965 TI - [Enzyme immunoassay of the level of parasite-specific IgE antibodies in schistosomiasis using the monoclonal antibody BL-IgE 9]. AB - Sera from patients with chronic schistosomiasis (Schistosoma mansoni or Schistosoma haematobium) were examined for the presence of parasite specific IgE antibodies by means of ELISA technique using tegument antigen prepared from adult worms of Schistosoma mansoni and using the monoclonal antibody BL-IgE 9. Individuals from tropical countries who had no schistosomiasis and blood donors from GDR were studied for comparison. Significantly higher levels of specific IgE antibody were given by sera from patients with schistosomiasis than by the controls. These differential responses serologically differentiated between patients with chronic schistosome infections and noninfected individuals. PMID- 2111966 TI - A comparative study in twelve mammalian species of volume densities, volumes, and numerical densities of selected testis components, emphasizing those related to the Sertoli cell. AB - Morphometric studies were performed on 12 mammalian species (degu, dog, guinea pig, hamster, human, monkey, mouse, opossum, rabbit, rat, stallion, and woodchuck) to determine volume density percentage (Vv%), volume (V), and numerical density (Nv) of seminiferous tubule components, especially those related to the Sertoli cell, and to make species comparisons. For most species, measurements were taken both from stages where elongate spermatids were deeply embedded within the Sertoli cell and from stages near sperm release where elongate spermatids were in shallow crypts within the Sertoli cell. Montages, prepared from electron micrographs, were used to determine Vv% of Sertoli cell components in seminiferous tubules. Excluding the tubular lumen, the Sertoli cell occupied from a high of 43.1% (woodchuck) to a low of 14.0% (mouse) of the tubular epithelium. There was a strong negative correlation (r = -0.83; P less than 0.005) of volume occupancy of Sertoli cells with sperm production. Nuclear volume, as determined by serial reconstruction using serial thick sections, ranged from a high of 848.4 microns 3 (opossum) to a low of 273.8 microns 3 (degu). There was no correlation (r = 0.02) of nuclear volume with volume occupancy (Vv%) in the tubule. Sertoli cell volume was determined by point counting morphometry at the electron-microscope level as the product of the nuclear size and points determined over the entire cell divided by points over the nucleus. Sertoli cell V ranged from 2,035.3 microns 3 (degu) to 7,011.6 microns 3 (opossum) and was highly correlated (r = 0.85; P less than 0.001) with nuclear size. However, there was no significant correlation between the Sertoli cell size (V) and volume occupancy (Vv%; r = 0.13) or sperm production (r = 0.21). Stereological estimates of the numerical density (Nv) of Sertoli cells ranged from a high of 101.9 x 10(6) (monkey) to a low of 24.9 x 10(6) (rabbit) cells per cm3 of testicular tissue. There was no correlation of numerical density of Sertoli cells with sperm production (r = 0.002). A negative correlation was, however, observed between the numerical density of the Sertoli cells and the Sertoli cell size (r = -0.79; P less than 0.002). Data from the present study are compared with those previously published. This is the first study to compare Sertoli cell morphological measurements using unbiased sampling techniques. Morphometric data are provided which will serve as a basis for other morphometric studies. PMID- 2111967 TI - Immunofluorescence localization of vinculin in ectoplasmic ("junctional") specializations of rat Sertoli cells. AB - We have investigated, using indirect immunofluorescence techniques, the possibility that vinculin is a component of Sertoli cell ectoplasmic specializations. Affinity-purified polyclonal antibodies produced against human platelet vinculin were used to probe fixed frozen sections of rat testis. Specific fluorescence occurs in Sertoli cell regions adjacent to spermatids and to basally situated junctional complexes, sites at which ectoplasmic specializations are known to occur. Staining also occurs in Sertoli cell regions associated with tubulobulbar complexes. The antibody also labels focal contacts in cultured human dermal fibroblasts, apical junctional sites of rat epididymal epithelium, and dense plaques of smooth muscle. Our results are consistent with the prediction that vinculin is likely a component of ectoplasmic specializations and are also consistent with the hypothesis that these structures are a form of actin-associated adhesion complex. PMID- 2111968 TI - The radiotherapeutic management of chordoid sarcoma. AB - Chordoid sarcoma is a rare neoplasm, with only 13 cases reported. In the past, the treatment of choice was excision or amputation, with radiation therapy reserved for metastases. This case report demonstrates the persistent nature and indolent course the tumor may have and its good response to high-dose irradiation. External beam irradiation, both photons and electrons, intraoperative radiation therapy, and 192-iridium implantation have all been successfully utilized for treatment of multiple recurrences in this patient. Doses of 6,000 cGy or greater were necessary to control the tumor in our patient, and this dose is recommended as adjuvant treatment following conservative (gross) tumor removal. PMID- 2111969 TI - Phase II assessment of recombinant leukocyte A interferon with difluoromethylornithine in disseminated malignant melanoma. AB - Sixteen patients with advanced melanoma received IFN-alpha 2A, 36 X 10(6) U/m2 i.m., on days 3-7 with 2.25 g/m2 DFMO p.o. on days 1-7. We observed no objective regressions. Median time to progression was 1.2 months with a median survival of 5.2 months. A flu-type syndrome was the predominant sequela. From the dose and schedule that we utilized, this regimen holds little promise against disseminated malignant melanoma. PMID- 2111970 TI - Advantages of a new anticoagulant in routine hematology on the Coulter Counter S Plus STKR analyzer. AB - The authors report the advantages of a new anticoagulant-antiaggregant mixture that avoids the deleterious effects of ethylenediaminotetraacetic acid (EDTA) on mean platelet volume and also prevents EDTA-induced platelet clumping. It is suitable for routine cell counting and sizing with the Coulter Counter S-Plus STKR. The values of the common hematologic parameters agree well with those from EDTA-treated samples and are stable for at least eight hours after sampling. PMID- 2111971 TI - The antiphospholipid syndrome: prevalence among patients with stroke and transient ischemic attacks. AB - PURPOSE: The prevalence of the antiphospholipid syndrome was determined prospectively in patients presenting with stroke and transient ischemic attacks. An attempt was made to define a subset of stroke patients at risk for this syndrome on the basis of their clinical features. PATIENTS AND METHODS: Fifty-one consecutive patients with stroke and transient ischemic attacks were assessed. Tests used for the laboratory diagnosis of the antiphospholipid syndrome included four phospholipid-dependent coagulation tests for detection of the lupus anticoagulant, and two enzyme-linked immunosorbent assays for antibodies to phospholipid. RESULTS: Three of 51 patients (6%, 95% confidence intervals 0% to 12.0%) had a lupus anticoagulant and the clinical features of the antiphospholipid syndrome. Seven patients had clinical features suggestive of the syndrome but negative laboratory tests. Those patients who were clinically unlikely to have this syndrome also had negative laboratory tests. CONCLUSION: In a series of 51 unselected patients presenting with stroke and transient ischemic attacks, three had the antiphospholipid syndrome. The clinical features of this syndrome are helpful in identifying this group of patients. The role of the lupus anticoagulant in the pathogenesis of stroke remains to be defined. PMID- 2111972 TI - AIDS and Chagas' disease with central nervous system tumor-like lesion. PMID- 2111973 TI - Retinal vasculitis. PMID- 2111974 TI - Multiple neurofibromatosis associated with mandibular growth and facial asymmetry. AB - Multiple neurofibromatosis develops with a plethora of clinical signs and symptoms. Oral manifestations have been reported only in 4% to 7% of the affected persons. Changes in the facial skeleton are sometimes associated with the disease. A rare case of multiple neurofibromatosis with pronounced facial asymmetry and mandibular overgrowth is presented and discussed. PMID- 2111975 TI - Regulatory role of arachidonic acid-derived metabolites for proliferation of transformed murine Leydig cell in serum-free culture condition. AB - The growth-regulatory ability of eicosanoids from arachidonic acid is poorly understood. To investigate their role in cell growth, we cultured transformed murine Leydig cells (B-1 or B-1 F) in serum-free medium supplemented with various compounds modulating arachidonic acid metabolism. The addition of 5-lipoxygenase inhibitors (AA 861, NDGA and quercetin) showed a growth-stimulative effect. On the other hand, their growth was remarkably inhibited by arachidonic acid added into the culture medium. This growth-inhibiting ability of arachidonic acid was almost completely reversed by a simultaneous exposure of B-1 cells to lipoxygenase inhibitor. Exogenously added 5-HETE inhibited cell proliferation in a dose-dependent manner. These results suggest that 5-lipoxygenase-catalyzed products from arachidonic acid have the ability to suppress the proliferation of some transformed cells. PMID- 2111976 TI - Dependence of cytokine-induced human myelogenous leukemic cell differentiation on the type of serum in the medium. AB - Human myelogenous leukemic cell lines (ML-1, U-937, THP-1) were induced to differentiate by treatment with various cytokines such as tumor necrosis factor, interferon-gamma and interleukin-6. However, the extent of cell maturation depended upon the types and concentrations of sera included in the culture medium. The stimulating activity of human sera on the cytokine-induced differentiation significantly exceeded that of various lots of calf serum, horse serum, fetal calf serum and fetal bovine serum, and its stimulating effects were reproducibly observed irrespective of age and sex of normal volunteers. On Sephadex G-200 gel filtration chromatography, the stimulatory substance(s) present in human sera were separated from the inhibitory substance(s) eluted near the void volume. PMID- 2111977 TI - Interferon gamma therapy for cutaneous leishmaniasis. PMID- 2111978 TI - Cutaneous manifestations of Pseudomonas infection in the acquired immunodeficiency syndrome. PMID- 2111979 TI - How much aerosol reaches the lungs of wheezy infants and toddlers? AB - Using sodium cromoglycate as a non-toxic marker, we assessed the delivery of aerosol to nine wheezy infants and seven healthy adults. The drug was delivered to the infants by face mask and spacer device from a metered dose inhaler, and by face mask and nebuliser to the infants and the adults who breathed though their noses. The concentration of sodium cromoglycate was estimated in timed urine collections to find out how much of the dose was absorbed from the lung. Only 0.13% to 0.61% of the 20 mg nominal dose was detected in the urine, representing an estimated 0.3% to 1.5% deposited in the lung. Nasal filtration of aerosol could be a critical factor in reducing lung deposition. PMID- 2111980 TI - Nebulised sodium cromoglycate in infancy: airway protection after deterioration. AB - Over a two year period 100 infants with histories of wheeze were challenged with nebulised water. They were sedated and lung function measured by total body plethysmography. Thirteen of the 53 infants who developed bronchoconstriction after challenge with nebulised water were given nebulised sodium cromoglycate and rechallenged with nebulised water. All infants were initially challenged with normal saline, after which there was no significant change in lung function. After challenge with nebulised water and sodium cromoglycate there were significant decreases in specific conductance compared with those found after challenge with normal saline. After rechallenge with nebulised water there was no deterioration in lung function. Although sodium cromoglycate caused a deterioration in lung function in these infants, it protected their airways from challenge with nebulised water. PMID- 2111981 TI - Albumin supplementation in the critically ill. A prospective, randomized trial. AB - Albumin replacement to correct hypoalbuminemia in critically ill patients has been controversial. This study was a prospective, randomized trial of 25% albumin administration in 40 hypoalbuminemic (serum albumin, less than 25 g/L [2.5 g/dL]), critically ill patients. The treatment group (18 patients) received 25% albumin supplementation to achieve and maintain serum albumin levels of 25 g/L (2.5 g/dL) or greater, while the nontreatment group (22 patients) received no concentrated albumin. There was no clinical benefit from albumin therapy when assessing mortality (39% vs 27%, treatment vs control) or major complication rate (89% vs 77% of patients). There were also no significant differences in length of hospital stay, intensive care unit stay, ventilator dependence, or tolerance of enteral feeding, despite significant elevations of albumin in the treatment group. The costly use of exogenous albumin as treatment for hypoalbuminemia in this patient population does not appear to be justified. PMID- 2111982 TI - A randomized clinical trial of prophylactic OKT3 monoclonal antibody in liver allograft recipients. AB - Seventy-nine hepatic allograft recipients were randomized to receive either conventional immunosuppression, including cyclosporine, azathioprine, and steroids (41 patients), or investigational therapy in which OKT3 replaced cyclosporine during the first postoperative week (38 patients). Early rejection occurred in 29 patients (71%) in the conventional group and 15 patients (39%) in the OKT3 group. Posttransplantation renal dysfunction occurred in 12 patients (29%) in the conventional group and 6 patients (16%) in the OKT3 group. Mean initial hospital stay was 34.1 +/- 18.8 days in the conventional group compared with 29.1 +/- 16.8 days in the OKT3 group. Cumulative patient survival (mean follow-up, 17.8 +/- 7.1 months) was 73.2% (30/41) for the conventional group and 84.2% (32/38) for the OKT3 group. Prophylactic OKT3 is indicated especially for liver allograft recipients with other complicating conditions that make management of early rejection unusually difficult. PMID- 2111983 TI - The use of glass ionomer cements for restoring occlusal tooth surfaces. PMID- 2111984 TI - Antibiotic resistance in general practice. AB - With the addition of several new oral antibiotics to those already available, there is the implication that bacterial resistance has become a significant problem in general practice. To test this hypothesis it is worth examining the susceptibilities of the major bacterial pathogens isolated from community based infections. PMID- 2111985 TI - Infectious diseases. Meningococcemia. AB - Late last year there was an increase in meningococcal disease in Melbourne and the author reviews the treatment procedures at the Alfred Hospital, Melbourne. The article is reprinted from the Alfred Hospital's Newsletter, which is edited by Dr Denis Spelman, Physician in Bacteriology. PMID- 2111986 TI - Influence of branched chain amino acid infusions on wound healing. AB - Branched chain amino acids (BCAA) may serve as a major oxidative fuel for skeletal muscle during periods of starvation. This study compared the ability of protein-undernourished rats to heal musculo-aponeurotic wounds of the abdominal wall when they were infused with solutions containing 45% BCAA or 8% BCAA (conventional TPN). Although the provision of 45% BCAA tended to result in better nourished animals and significantly increased plasma glutamine concentrations, this was not associated with improved healing. PMID- 2111987 TI - Genotype and anesthetic determine mate choice in Drosophila melanogaster. AB - Genetic differences that influence mating preferences were studied in genetically defined lines of Drosophila melanogaster. Initial results suggested substantial differences between two types of females with respect to the types of male preferred as mates, but further experimentation showed that the mating patterns were conditional on the mode of anesthesia (CO2 versus ether). In a statistical test of independence, the major determinant of mating choice in these experiments was due to an interaction effect between genotypes and mode of anesthesia. The observations might be explained by the differential sensitivity of male genotypes to ether. Etherization at emergence has lasting effects on mating behavior; it alters not only the latency and frequency of mating 4 days later, but also the pattern of matings observed. PMID- 2111989 TI - Transcriptional activation by TGF beta 1 mediated by the dyad symmetry element (DSE) and the TPA responsive element (TRE). AB - Transforming growth factor beta 1 (TGF beta 1) is a multifunctional regulator of growth and differentiation. However, both cytoplasmatic and nuclear signal transduction mechanisms leading to the biological effects of TGF beta 1 are largely unknown. In this report we show, that TGF beta 1 induces the expression of the immediate early genes c-jun and jun B, that encode trans-acting factors regulating transcription of a variety of genes in response to growth factors and phorbol esters. The jun genes are induced by TGF beta 1 in a protein synthesis independent fashion both in quiescent mouse 3T3 fibroblasts, which are growth stimulated by TGF beta 1, as well as in mink lung CCL64 (ML-CCL64) epithelial cells, which are growth inhibited by TGF beta 1. The PDGF inducible JE gene was induced by TGF beta 1 in 3T3, but not in ML-CCL64 cells. Furthermore, we show that chimaeric reporter-CAT constructs containing the TPA responsive element (TRE) or the dyad symmetry element (DSE) are activated by TGF beta 1 in transient transfection assays in both growth inhibited and growth stimulated cells. These results show that the early genomic responses to TGF beta 1 resemble changes in gene expression induced by serum, growth factors and phorbol esters, suggesting common mechanisms of transcriptional activation. PMID- 2111988 TI - Heat shock induces the transcriptional activation of c-fos protooncogene. AB - Treatment of murine 3T3 fibroblasts with mild elevated temperature (43 degrees C for 45 minutes) followed by recovery at 37 degrees C induced high levels of c-fos mRNA. The maximal c-fos induction was found after recovery at 37 degrees C for 15 minutes. Sodium arsenite induced both hsp 70 and c-fos transcripts. Induction of hsp 70 and c-fos by heat shock did not require intact protein synthesis. c-fos mRNA induced by heat shock was more stable (T1/2 greater than 90 minutes) than that induced by phorbol esters (t1/2 approximately 30 minutes). Northern blot analysis in the presence of actinomycin D and nuclear run off experiments demonstrated that heat shock augmented the transcription rate of c-fos protooncogene. Human growth hormone under the control of a murine genomic c-fos fragment spanning 770 bp 5' from the start of transcription is induced in transfected cells in response to heat shock. These data indicate that heat shock induces c-fos protooncogene acting at both transcriptional and post transcriptional (i.e. via stabilization of transcripts) levels. PMID- 2111991 TI - Target of serine inhibition in Escherichia coli. AB - L-serine has long been known to inhibit growth of Escherichia coli cells cultured in minimal medium supplemented with glucose, lactate, or another carbohydrate as the sole source of carbon. However, the target of serine inhibition was not known. The growth inhibition was released by adding isoleucine, 2-ketobutyric acid, threonine or homoserine, but not by aspartate. Thus the inhibition site must be between aspartate and homoserine in the isoleucine biosynthetic pathway. We found that homoserine dehydrogenase I was strongly inhibited by serine. We isolated serine-resistant mutants, and found that in these mutants homoserine dehydrogenase I was resistant to serine. Thus, we conclude that the target of serine inhibition in Escherichia coli is homoserine dehydrogenase I. PMID- 2111990 TI - Soluble factors including proteinases released from damaged cells may trigger the wound healing process. AB - The wound healing process is initiated as soon as tissue is injured. Herein, we demonstrate that c-fos and c-myc mRNA transcripts are promptly increased in the wounded tissue in vivo and in vitro. A buffer solution from scraped serum-starved quiescent fibroblasts, when added to resting fibroblasts, caused the increase of c-fos and c-myc mRNA among the indicator cells. Soluble factors contained in the wounding supernatant are responsible for these phenomena and we call them wounding factors. Addition of proteinase inhibitors to the culture medium drastically reduced the c-fos mRNA induction by the wounding factors. Exogenously added trypsin or thrombin mimicked the activity of wounding factors. These results suggest that wounding causes soluble factors including various proteinases to be released from the damaged cells, which trigger the adjacent cells to respond to the injury. PMID- 2111992 TI - A small GTP-binding protein (G protein) recognized by smg p25A GDP dissociation inhibitor (GDI) in human platelet membranes and GDI for this small G protein in human platelet cytosol. AB - We have recently purified from bovine brain cytosol a novel type of regulatory protein for smg p25A, named smg p25A GDP dissociation inhibitor (GDI), that regulates the GDP/GTP exchange reaction of smg p25A by inhibiting the dissociation of GDP from and thereby the subsequent binding of GTP to it. This smg p25A GDI is inactive for other ras p21/ras p21-like small GTP-binding proteins (G proteins) including c-Ha-ras p21, smg p21, rhoA p21 and rhoB p20. In human platelet membranes, smg p25A was not detected but a G protein with an apparent Mr value of 24,000 (24KG) was recognized by smg p25A GDI and the dissociation of GDP from and the binding of GTP to 24KG were inhibited by smg p25A GDI. The doses of smg p25A GDI necessary for these activities for both 24KG and smg p25A were the same. This 24KG was not recognized by an anti-smg p25A monoclonal antibody. The GDI activity for human platelet 24KG and smg p25A was detected in human platelet cytosol. This human platelet GDI was recognized by an anti-smg p25A GDI polyclonal antibody. These results indicate that there is a 24KG-24KG GDI system similar to a smg p25A-smg p25A GDI system in human platelets. PMID- 2111994 TI - The carbohydrate side chains of the major plasma serpins of horse and wallaby: analyses of enzymatic and chemically treated (including 'Smith degradation') protein blots by lectin binding. AB - The carbohydrate side chains of the major plasma serpins of the horse and wallaby have been characterized by lectin analyses of protein blots from two-dimensional gels using the major human plasma serpin, alpha 1-protease inhibitor, as a control. Eight lectins were used in the characterization in conjunction with enzymatic deglycosylation of complex and high mannose side chains, chemical desialylation and defucosylation, and one round of 'Smith degradation', all being performed on the nitrocellulose blots. Assuming a standard complex side chain structure, the results of the 21 lectin/treatment combinations were interpreted as indicating that the equine proteins consist of partially sialylated biantennary side chains except for the most acidic proteins which have triantennary side chains. The wallaby proteins have bi- and triantennary side chains with a bisecting N-acetylglucosamine and fucose residue present. PMID- 2111993 TI - proTRH gene expression by fetal pancreatic islets in culture. AB - The hypothalamic tripeptide, thyrotropin-releasing hormone (TRH), has been detected in neonatal pancreatic tissue and localized by immunocytochemistry in the islets of Langerhans. To determine whether the TRH gene is expressed in islets, we have extracted RNA from cultured rat islets and probed for proTRH mRNA using a [32P]-labeled antisense RNA. Islet proTRH mRNA comigrated with the 1.6 kilobase proTRH mRNA present in the rat hypothalamus. Normalized to total RNA, islets cultured for 7 days contained at least 10 times more proTRH mRNA than day 1 whole pancreas. We conclude that pancreatic TRH is synthesized in situ in the islets of Langerhans. This is the first attempt to characterize and quantify proTRH mRNA using neoformed foetal islets. We propose that quantitative analysis of proTRH mRNA concentrations in this culture system will enable study of the direct regulation of TRH biosynthesis in the pancreas. PMID- 2111995 TI - Biosynthesis of prostaglandins in ovarian follicles and corpus luteum of sheep ovary. AB - The biosynthetic potential of prostaglandins (PGs) was measured in ovarian follicles and corpus luteum of sheep ovary. The total prostaglandins formed under non-enzymatic conditions were much lower in comparison to that formed using native GSTs. When the GSTs of ovarian follicles were employed, the major prostaglandin formed was PGE2 (81.22%) followed by PGD2 (16.9%) and PGF2 alpha (1.87%). In case of corpus luteum, prostaglandin formed was PGF2 alpha (59.01%). Since PGF2 alpha was demonstrated to be the luteolytic factor, the present study indicates the formation of luteolytic factor in the ovarian tissue itself. PMID- 2111996 TI - Fructose-1,6-bisphosphate aldolase preferentially associates to glyceraldehyde-3 phosphate dehydrogenase in a mixture of cytosolic proteins as revealed by fluorescence energy transfer measurements. AB - Fluorescence energy transfer measurements were implemented for demonstrating the specific character of the interaction between aldolase and glyceraldehyde-3 phosphate dehydrogenase. The enzymes, labeled with monobromobimane (donor) and fluorescein isothiocyanate (acceptor), respectively, were mixed into a cytosol preparation and energy transfer between the two fluorophores was observed to develop. This observation reflecting a contact between the two enzymes, suggests that despite the presence of a multitude of potential macromolecular partners glyceraldehyde-3-phosphate dehydrogenase and aldolase are capable of recognizing each other in the cytoplasm. The idea that in vivo associations of metabolically sequential enzymes may be of physiological benefits is consistent with this result. PMID- 2111997 TI - On the role of peripheral interactions in specificity of chymosin. AB - Chymosin is distinguished by a high level of milk-clotting activity which is the consequence of the specific cleavage of the Phe(105)-Met(106) bond of kappa casein. Based on modelling considerations it was proposed that milk-clotting activity of chymosin is associated with electrostatic interactions of a charged segment His-Pro-His-Pro-His (98-102) of casein and the outer loop of the enzyme containing Glu-244,Asp-246 and Asp-248. PMID- 2111998 TI - [Modification of hemoglobin by glutaric aldehyde and electrochemical properties of the conjugates]. AB - Electrochemical properties of macromolecules of modified haemoglobin obtained by polycondensation with glutaric aldehyde have been investigated by means of potentiometric titration, PAG-electrophoresis, ion-exchange chromatography, and (for evaluation of isoelectric point) distribution between two aqueous polymeric phases. Introduction of additional functional groups into the macromolecule is possible by using various agents blocking polycondensation, which makes it possible to change the resulting charge and the isoelectric point. PMID- 2111999 TI - Effect of amperozide on the dopamine synthesis activity in the tuberoinfundibular neurons. AB - The ability of amperozide (N-ethyl-4-[4,4-bis(p-fluorophenyl)butyl]-1 piperazinecarboxamide) , a potentially antipsychotic agent, to activate the tuberoinfundibular dopamine (TIDA) neurons was studied by measuring the accumulation of dihydroxyphenylalanine (DOPA) in the median eminence after inhibition of DOPA decarboxylase. The activity of the TIDA neurons was markedly elevated in a dose-related manner after treatment with amperozide (1 and 10 mg/kg). A significant stimulation was also found following treatment with the atypical antipsychotic agent clozapine (20 mg/kg) while the typical antipsychotic drug haloperiodol had no effect on TIDA neuron activity. The stimulatory effect of amperiozide on the TIDA neurons is suggested to be mediated by a non dopaminergic mechanism. PMID- 2112000 TI - Tissue selectivity of the novel calcium antagonist sesamodil fumarate in isolated smooth muscles and cardiac muscles. AB - The effects of the novel Ca2+ antagonist sesamodil fumarate (JAN), (+)-3,4 dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3,4- methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H- 1,4 benzothiazine hydrogen fumarate (SD-3211), on isolated smooth muscles and cardiac muscles were investigated and compared with those of diltiazem, verapamil, nifedipine and nicardipine. Ca2+ antagonistic activity of SD-3211 (pA2 = 8.42) was more potent than that of diltiazem and verapamil, but less potent than that of nifedipine and nicardipine in isolated pig coronary artery. The inhibition of Ca2(+)-induced contraction by SD-3211 was not reversed by drug washout, whereas that by diltiazem was easily reversed by drug washout. SD-3211 produced a concentration-dependent relaxation (EC50 = 5.7 x 10(-8) mol/l) of KCl-contracted pig coronary artery. The order of potency of the various compounds correlated with their respective Ca2+ antagonistic activities. SD-3211 antagonized KCl induced contraction, but not that induced by A23187, in the rabbit aorta. On the other hand, negative inotropic and chronotropic effects of SD-3211 on the guinea pig right atria approximated those of diltiazem and verapamil. These results suggest that SD-3211 exerts a potent and long-lasting Ca2+ antagonistic effect on isolated arteries, possessing pharmacological properties diverse from those of known Ca2+ antagonists with respect to tissue selectivity, i.e., it is more vasoselective than diltiazem and verapamil, and more cardioselective than nifedipine and nicardipine. PMID- 2112001 TI - Metabolic fate of exogenous chondroitin sulfate in the experimental animal. AB - After the administration of tritiated chondroitin sulfate (CS) by oral and intramuscular route, the distribution of radioactivity was investigated in two opportunist omnivorous animals, namely the rat and the dog. More than 70% of the orally administered radioactivity was absorbed. Independently of the administration route, radioactivity was mainly excreted through the urine. Plasma levels showed a rapid increase after oral administration, followed by a large plateau with a maximum at the 14th and 28th h in the rat and in the dog, respectively. A tropism of the radioactivity was observed towards glycosaminoglycan-rich tissues, such as joint cartilage. The analysis of the molecular weight of the radioactive material showed that compounds with a molecular weight corresponding to those of CS, poly-, oligo- and monosaccharides as well as of tritiated water, were present in the plasma, urine, synovial fluid and cartilage. The level of radioactive low molecular weight material, derived from the metabolism of CS and from the exchange reaction, increased with the time after administration. The high molecular weight fraction represented at least 10% of the orally administered CS. PMID- 2112002 TI - [Manganese determination in blood from malnourished children]. AB - We investigated the serum manganese (Mn) concentration of 52 children less than two years old. 22 of them were healthy controls (C), 13 had marasmatic (M) malnutrition and 17 kwashiorkor (K). The measurements of Mn were done in an atomic absorption spectrophotometer with a graft furnace oven. The serum was diluted with 1% triton X-100. For the quantification of Mn we used the addition method. There was a significant difference between the levels of Mn measured in the M group (1,582 +/- 0.673 micrograms/L), and the K group (1,811 +/- 0.700 micrograms/L) and levels obtained in the controls (3,212 +/- 1,247 micrograms/L). When we compared the concentration of Mn by sex or age in each group, we didn't find any significant difference. We conclude that the severe malnourished children in our study present lower concentrations of Mn as compared with controls. PMID- 2112003 TI - Injections of 6-hydroxydopamine in the substantia nigra of the rat brain: morphological and biochemical effects. AB - Rats with unilateral injections of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta were classified as active and inactive according to the intensity of their spontaneous and/or apomorphine-induced turning behavior (TB), and sacrificed at different survival times for morphological and biochemical analysis. In active rats, at any survival time, dopaminergic fluorescence in the nigrostriatal system as well as dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) content of the nucleus caudatus-putamen drastically decreased on the brain side ipsilateral to the injection. Dopaminergic fluorescence as well as DA and DOPAC content of the mesolimbic system ipsilateral to the injection also decreased. In inactive rats, at any survival time, 6-OHDA-induced lesions only partially involved both nigrostriatal and mesolimbic systems. Our results are indicative of a good correlation between the intensity of TB and the extent of 6 OHDA-induced lesions, as assessed by morphological and biochemical analysis. PMID- 2112004 TI - Relevance of vascular PGI2 synthase to vascular prostacyclin production in Dahl rats susceptible to salt-induced hypertension. AB - To assess the roles of prostacyclin (PGI2) synthase in vascular PGI2 generation, the enzymatic activity was examined in the mesenteric artery of Dahl S rats in the prehypertensive or hypertensive stage. Elevation of blood pressure in Dahl S rats was accompanied by an increase of vascular PGI2 synthase activity. The enzymatic activity was positively correlated to the blood pressure value. Similarly, impaired vascular capacity to generate PGI2, which was observed in prehypertensive Dahl S rats, was restored to the control level of Dahl R rats with the elevation of blood pressure. These data indicate that vascular PGI2 synthase activity is increased with blood pressure elevation, thereby contributing to the restoration of vascular capacity to generate PGI2 in Dahl S rats. PMID- 2112005 TI - The effect of varying alveolar carbon dioxide levels on free recall. AB - A recent study suggested that students who have increased minute ventilation receive poorer grades. The present study was interested in determining the role alveolar carbon dioxide (CO2) levels play with cognitive abilities. A free recall task was used to examine list learning under two conditions of alveolar CO2 level: normal and decreased. The results suggested that decreased alveolar CO2 level affect the participant's ability to rehearse and recall information. It was concluded that conditions that reduce alveolar CO2 levels, such as hyperventilation resulting from stress, nervousness, or inappropriate breathing habits, can lead to poorer learning. If these conditions produce a habitual breathing pattern, the academic performance of the individual may suffer. PMID- 2112006 TI - Ca2+ uptake during capacitation of mouse spermatozoa and the effect of an anion transport inhibitor on Ca2+ uptake. AB - With a specially constructed chamber, Ca2+ uptake by mouse spermatozoa was monitored continuously during capacitation and the acrosome reaction. It was shown, using calcium ion-selective microelectrodes, that there was an initial uptake of Ca2+ by spermatozoa undergoing capacitation. Such net transport was also promoted by the divalent cation ionophores A23187 or ionomycin. An anion inhibitor, SITS, produced dose-dependent inhibition of Ca2+ uptake. This inhibitor reduced the incidence of capacitation as revealed by a reduction in the B pattern by chlortetracycline (CTC) assay and thus inhibited fertilization, suggesting that anions are involved in calcium uptake in mouse spermatozoa. PMID- 2112007 TI - Does the expired carbon dioxide waveform suggest endobronchial intubation? PMID- 2112008 TI - The immunocytochemical detection of cytochrome P-450 monooxygenase in the lungs of fetal, neonatal, and adult hamsters. AB - Antibodies against rabbit cytochrome P-450 reductase (reductase), cytochrome P 450 isozyme 2 (P-450 IIB), and cytochrome P-450 isozyme 5 (P-450 IVB) were used to detect homologous enzymes in the developing lung of the Syrian golden hamster. No immunocytochemical labeling was observed on gestational days 11, 12, and 13. On gestational day 14, light immunoperoxidase labeling for reductase and P-450 IIB was observed over cells lining the trachea and cranial portions of lobar bronchi. On gestational day 15, these enzymes were detected in conducting airways at all anatomic levels, and in the media of the pulmonary vein and its branches. Light labeling for P-450 IVB was first observed over cells lining the trachea and lobar bronchi on gestational day 15, but the smallest bronchioles and the media and endothelium of the pulmonary vein did not label for this enzyme until gestational day 16 (neonatal day 1). Type II pneumocytes and the pleural mesothelium first labeled for each of the three enzymes on neonatal day 1. Although the mesothelium no longer labeled for reductase or P-450 IIB in hamsters 3.5 wk old, the other labeling sites persisted in adult hamsters. Because cytochrome P-450 enzymes are associated with the endoplasmic reticulum, an ultrastructural examination of differentiating secretory cells was made to detect its appearance. At each conducting airway level, smooth endoplasmic reticulum was present in the cells 2 d before cytochrome P-450 enzymes could be detected immunocytochemically. The appearance of these enzymes paralleled the development of the hamster lung; they were first present in the trachea and lobar bronchi, then in the bronchioles, and finally in the alveoli. PMID- 2112009 TI - Postnatal development of the glycine cleavage system in rat liver. AB - The development of the glycine cleavage system was studied in liver mitochondrial extracts from neonatal and adult rats. The enzyme activity in 2-day-old pups was 29.3% of that measured in the adult and was found to increase in an age-dependent manner. Measurement of hepatic free amino acid concentrations at the neonatal ages showed that glycine levels were highest at 2 days and at 14 days were about 48% of those in the 2-day-old pups. Serine levels did not change between the age of 2 and 14 days. A developmental delay in the glycine cleavage system is responsible for the high levels of glycine in the neonatal rat liver. PMID- 2112010 TI - General practice consultation patterns before and after intentional overdose: a matched control study. AB - This study investigated the general practice consultations of 46 patients during the year before and 13 weeks after hospital admission for deliberate self poisoning. These were compared with data for controls matched for age, sex, family structure and area of residence. The frequency of consultations increased as parasuicide approached but this effect was due to large increases in a few patients. The greatest increase in the number of consultations and an increase in subjects consulting for physical problems occurred four to six months before the event. The seriousness of the attempt assessed by suicidal intent was unrelated to consulting pattern either before or after overdose. The rate of default from appointments was less than for controls, although this was not significantly different. Because of the problems in identifying when intentional self-harm will occur and the common presentation being psychosocial distress rather than mental illness, intervention to prevent parasuicide is likely to prove even more difficult than for suicide. PMID- 2112011 TI - Do general practitioners and health visitors like 'parent held' child health records? AB - The study examines the reactions of general practitioners and health visitors to parents holding the main record of their own child's health and development. From 1986 the parents in part of the Oxfordshire district were given their child's records while in the other part of the health district the records remained with the clinic. The responses to questionnaires sent out to all general practitioners and health visitors in the two areas were analysed and compared. The results show that over 90% of the general practitioners and health visitors with experience of parent held records are in favour of them, wish to continue to use them, find them to be available in the clinic and are able to use them at other times. By comparison only 59% of those general practitioners who had no experience of parent held records are in favour of such a scheme. In general this latter group show greater concern in almost all areas investigated. Thus general practitioners' and health visitors' experience of the record suggests that it is not only workable but actually desirable. PMID- 2112012 TI - Infection control procedures among New Zealand general practitioners: changes since the emergence of HIV infection. AB - A random sample of 1000 general practitioners in New Zealand were surveyed to assess their infection control procedures in the surgery, particularly since the emergence of the human immunodeficiency virus (HIV). Forty three per cent of the sample routinely used surgical gloves for minor surgical procedures, 8% used gloves for venepuncture, and 7% for blood glucose testing. Thirty two per cent reported a change in glove use since the emergence of HIV infection. Changes in sterilization procedures were also studied. Thirty eight per cent of the sample reported increased use of disposable equipment, and 38% reported changes in the sterilization solution used. Increased time spent by equipment in the sterilizer was reported by 33% of respondents and increased use of an autoclave by 18%. In general, women were more likely to have adopted infection control procedures than men. Infection control was also more common among those doctors having the greatest number of patients requesting HIV testing. PMID- 2112013 TI - Prevalence of iron deficiency in rural pre-school children in Northern Ireland. AB - Screening for iron deficiency was offered to 485 pre-school children in one practice. A questionnaire asking for details of the child's birth, diet, medical history and social status was sent to all the families of these children. Three hundred and eleven children (64% of the total) had blood samples taken for haemoglobin concentration, mean corpuscular volume and serum ferritin levels. Fifty four of the children (17%) were iron deficient (serum ferritin less than 10 micrograms l-1 or mean corpuscular volume less than 75 fl), while 10 (3%) had iron deficiency anaemia (haemoglobin level less than 10.5 g dl-1). The prevalence of iron deficiency and iron deficiency anaemia were not significantly associated with any social class. However, there was a higher prevalence among social class 3 children than children from other social classes, 29% of them having covert iron deficiency, while 6% were frankly anaemic. As there are no ethnic minorities in the practice, dietary inadequacy was likely to be the main cause of iron deficiency. After receiving iron supplements for up to three months, all the children who were iron deficient or anaemic and attended for follow up had normalized blood values. In view of the high prevalence of iron deficiency throughout the social classes, and its association with developmental delay and behavioural disorders, screening will be offered to all children when they attend for measles, mumps and rubella immunization, and those who do not attend will be followed up. PMID- 2112014 TI - A review of the factors associated with patient compliance and the taking of prescribed medicines. AB - Patient non-compliance is an ever present and complex issue, the importance of which is likely to increase in successive years as the population ages. Non compliant behaviour is not only costly in terms of time, money and resources, but can also be detrimental to the doctor-patient relationship. Assessment of the prevalence and nature of non-compliance is difficult, but several determinant factors have been found to be associated with it. The aim of this review is to consider these factors and so increase the doctor's awareness of this problem. PMID- 2112016 TI - Open access to spirometry with chest x-ray. PMID- 2112015 TI - Resources, the family and voluntary euthanasia. AB - Ethnological studies show that the care which societies are able to provide for their old people depends largely on available resources. However, the concept of resource depends on contemporary requirements and expectations. Modern families still try to look after their old people, but increasing longevity is making this more difficult. There is a finite ability of populations, however wealthy, to support dependent members. Resources provided to look after old people must necessarily be subtracted from those available for the other, still more important dependent group, the children, with potentially disastrous results in underfunding of social support and education. The sociobiological theory of inclusive fitness emphasizes the importance of the ways in which family members interact to help each other and try to ensure their genetic survival, even if this involves sacrificing their own interests and occasionally, their lives. Many old people do not wish for further longevity after they have become too disabled to be of service to their families, and would prefer to see limited resources being used for the young. In the USA, loss of autonomy of patients and their families owing to the practice of defensive medicine has resulted in the development of the 'living will', a legal document in which people can specify in advance what treatment they wish to accept in the event of life threatening illness. It is to be hoped that improved understanding of family relationships will make this generally unnecessary in the future and that, unless specified to the contrary, families will be allowed to decide about treatment for members who are unable to decide for themselves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112017 TI - Exotic disease in a traveller? A case of leptospirosis. PMID- 2112018 TI - Pneumatic otoscopy and tympanometry. PMID- 2112019 TI - General practice in the 1840s. PMID- 2112020 TI - Nineteen ninety two. PMID- 2112021 TI - Double agent. PMID- 2112023 TI - [Single diverticulum of perforated cecum. Report of 5 cases]. AB - Cecal diverticulitis is a relatively rare disease, which closely mimics the picture of acute appendicitis. At times it is difficult to differentiate from carcinoma. Five cases of cecal diverticulitis are reported, with a discussion of some salient features of this condition. Although two cases were treated with a right hemicolectomy, a plea for conservatism in the treatment of this disease is made. PMID- 2112022 TI - Screening elderly people in primary care: a randomized controlled trial. AB - A randomized controlled trial was carried out to test the effectiveness of a screening programme carried out by nurses for elderly people aged 75 years and over in a general practice. A total of 151 people were randomly allocated to the test group and 145 to the control group. The test group received a home visit from a nurse at which an assessment lasting 45 minutes was made of: activities of daily living, social functioning, sensory functions, mental and emotional problems, current medical problems, blood pressure, urinalysis, haemoglobin level and compliance with medication. Both groups completed a selection of items from four health indices before and 20 months after the intervention. At follow up, the test group scored significantly better than the control group on a morale scale. However, this trial provided no evidence for better resolution of physical problems or finding activities of daily living easier in the test group compared with the control group. It is suggested that the main benefit of such a screening process is that the special attention and education provided improves adaptation to old age and awareness of the support systems available. The government has proposed an annual review of elderly people in their own home and this study suggests that the objectives of this scheme should be clarified. PMID- 2112024 TI - [Isolated diverticulum of the cecum]. PMID- 2112025 TI - Light chain restriction analysis of bone marrow plasma cells in patients with MGUS or 'solitary' plasmacytoma: diagnostic value and correlation with clinical course. AB - Twenty-eight patients with a diagnosis of 'solitary' plasmacytoma or with gammopathy but with nondiagnostic morphologic examination of the bone marrow were investigated using a short-term bone marrow culture technique which enriched for the plasma cell fraction. The percentage of monotypic plasma cells in these plasma cell enriched cultures was correlated with the subsequent clinical course. The majority of patients with plasmacytoma and a significant number of those with gammopathy but with otherwise non-diagnostic investigations were found to have a monoclonal plasma cell component of greater than 20%. There was a significant correlation between the percentage of monoclonal plasma cells as detected by bone marrow culture and subsequent progression to disseminated myeloma. These results indicate that early bone marrow involvement can be detected by means of plasma cell culture prior to morphologic identification of marrow plasmacytosis and that short-term plasma cell culture distinguishes patients with early, low bulk myeloma from those with monoclonal gammopathy of uncertain significance (MGUS). PMID- 2112026 TI - Murine monoclonal antibodies directed to the human histo-blood group A transferase (UDP-GalNAc:Fuc alpha 1----2Gal alpha 1----3-N acetylgalactosaminyltransferase) and the presence therein of N-linked histo-blood group A determinant. AB - Mouse MAbs (WKH-1 through -3) to the human histo-blood group A glycosyltransferase (Fuc alpha 1----2Gal alpha 1----3 galactosaminyltransferase) were established by immunization with the purified native A transferase protein. Hybridomas were selected on the basis of solid-phase reactivity with the purified native A transferase, cell immunofluorescence and immunoprecipitation of transferase activity, and absence of reactivity with blood group ABH carbohydrate determinants. Three MAbs, thus selected, were found most likely to react with the protein epitopes unrelated to carbohydrate epitopes of purified A transferase. The MAbs reacted with cells having high A transferase activity and immunoprecipitated the A transferase activity as well as the 40,000 MW iodinated transferase protein. The antibodies were shown, however, to immunoprecipitate and partially inhibit not only A1 and A2 but also B transferase activity from plasma and A transferase from human lung, and to react with B cells expressing B transferase, thus indicating a cross-reactivity with B transferase. In contrast, they showed no reactivity with various cells having the O phenotype and did not immunoprecipitate the A transferase from porcine submaxillary glands or the alpha 1----2fucosyltransferase from Colo205 cells. The purified A glycosyltransferase was found to carry blood group A carbohydrate determinants by immunochemical detection with a panel of anti-carbohydrate MAbs. These determinants are believed to be N-linked, since treatment of the purified A transferase with N-glycanase removed activity. Immunohistological studies of three epithelial tissues showed that the antibodies stained the Golgi area of cells in epithelia from A and B, but not O, individuals. PMID- 2112027 TI - Blockade of the selective increase in serum follicle-stimulating hormone concentration in immature female rats and its effects on ovarian follicular development. AB - We investigated whether administration of monosodium L-glutamate (MSG) to neonatal female rats would block the selective increase in serum follicle stimulating hormone (FSH) concentration in immature rats in an attempt to provide a model in which to study the importance of the selective FSH rise on ovarian follicular development. In two separate experiments, s.c. injections of MSG (4 mg/g BW) on Days 1, 3, 5, 7 and 9 after birth blocked the selective increase in serum FSH concentration observed on Days 7 and 15 without blocking basal FSH secretion. Serum luteinizing hormone (LH) levels were unaffected in the first experiment and changed little in the second. MSG-treated rats had smaller ovaries on Days 15 and 23. The ovaries of MSG-treated rats on Day 15 showed decreased follicular growth as evidenced by a decrease in the number and percentage of follicles with diameters greater than 50 microns, in the number of follicles with greater than 1 layer of granulosa cells, and in the number of follicles beyond the primary stage of follicular development. These differences between MSG treated rats and controls all but disappeared by Day 23. The results demonstrate that neonatal administration of MSG blocks the selective increase in serum FSH concentration in immature female rats and suggest that this selective increase in serum FSH levels plays a role in the normal acceleration of ovarian follicular development but is not needed for the development of preovulatory follicles by the sixth week after birth. PMID- 2112028 TI - Age-related alterations in follicular development and hormonal profiles in rats with 4-day estrous cycles. AB - Two experiments were conducted to examine the hypothesis that an alteration in follicular development is associated with advancing maternal age in the absence of prolonged estrous cycles. In Experiment 1, serum and four follicles (from one ovary per rat) were collected from young and middle-aged, 4-day cycling rats on estrus or metestrus. Number and diameter of nonatretic antral follicles greater than 200 microns in diameter were determined from serial sections of the other ovary from each rat. In Experiment 2, serum and follicles (12 +/- 2) from both ovaries were collected from young and middle-aged rats on each day of a 4-day estrous cycle. All microdissected follicles were assayed for estradiol-17 beta (E2) and all sera were assayed for E2, follicle-stimulating hormone, and luteinizing hormone by radioimmunoassay. Numbers of follicles greater than 400 microns in diameter did not differ, while numbers of follicles 200-400 microns in diameter were reduced in middle-aged rats compared to young rats (Experiment 1). The mean diameter of follicles greater than 400 microns in diameter and the follicular content of E2 was greater in middle-aged than in young rats. In Experiment 2, a greater proportion of large follicles were observed in middle aged rats than in young rats on all days, and a greater proportion of follicles with high concentrations of E2 were observed on diestrus. We interpreted these data as indicative of an early age-related change in the control of follicular recruitment, growth, and maturation. PMID- 2112029 TI - The seminiferous growth factor induces proliferation of TM4 cells in serum-free medium. AB - The seminiferous growth factor (SGF) of the mammalian testes induces DNA synthesis and cell proliferation of Balb/c 3T3 cells (Bellve and Feig, 1984; Rec Prog Hormone Res 40:531-567). In this study, SGF was purified 80,000- to 100,000 fold from calf testes and used to examine the growth of TM4 cells in a chemically defined medium. Cells were seeded sparsely in Dulbecco's Modified Eagles/Ham's F12 medium (1:1;v:v) (DME/F12 degrees), containing epidermal growth factor (EGF; 1 ng/ml), insulin (1; 10 micrograms/ml), and transferrin (Tr; 5 micrograms/ml) (DME/F12). After 24 h, the medium was replaced with DME/F12 degrees supplemented with SGF, EGF, 1, or Tr, in two-, three- or four-way combinations. Cell numbers were quantified after another 48 h of culture. EGF, I, and Tr, alone or in two way combinations, were not mitogenic for TM4 cells. By contrast, SGF (1 U) alone, or with any two of these factors, stimulated TM4 cell proliferation to commensurate levels, and to twofold greater numbers than occurred with the combination of EGF, I, and Tr. Synergisms or inhibitions were not measurable. Follicle-stimulating hormone, luteinizing hormone, prolactin, acidic fibroblast growth factor, or basic fibroblast growth factor was weakly or not mitogenic for TM4 cells. The effect of SGF on cell proliferation was inhibited by 1 microM - 1 nM retinoic acid, but not by retinol or retinyl acetate. SGF was mitogenic for bovine adrenal capillary endothelial cells, an effect that was potentiated by 10 micrograms heparin/ml. Thus, SGF can induce proliferation of TM4 cells and capillary endothelial cells. The former provides a sensitive, and selective, serum-free, bioassay system for SGF activity. PMID- 2112030 TI - Histochemical localization and quantification of alpha-glucosidase in the epididymis of men and laboratory animals. AB - The seminal marker of epididymal function alpha-1, 4-glucosidase was localized histochemically in the cytoplasm of the efferent duct epithelium and the brush border of the entire length of the human epididymis. Quantification using the specific inhibitor castanospermine revealed strongest activity in the corpus and cauda regions. Selective inhibition of the brush border enzyme activities by maltotriose identified these as the neutral isoenzymes. Despite detection of alpha-glucosidase in the renal tubules of all the animals studied, the enzyme was not detectable in epididymides of hamsters or mice. In rabbits and monkeys, it was absent from the entire brush border but present weakly in the cytoplasm of the proximal epididymides. An enzyme distribution pattern similar to that in the human epididymis was found in rats, except for the absence of histochemical staining at pH 6.5 from the initial segment and distal cauda epididymidis. Experiments in which endogenous testosterone was depleted in rats demonstrated the dependence of epididymal alpha-glucosidase on androgen, albeit with a low sensitivity. This study suggests the rat to be a suitable model for the investigation of the role of epididymal alpha-glucosidase in fertility. PMID- 2112031 TI - Gamma-interferon modulates von Willebrand factor release by cultured human endothelial cells. AB - Endothelial cells (EC) synthesize and secrete von Willebrand factor (vWF), a multimeric glycoprotein required for normal hemostasis. Within human endothelial cells, vWF multimers of extremely high molecular weight are stored in rod-shaped organelles known as Weibel-Palade bodies. Inflammatory mediators, such as interleukin-1, induce in vitro a variety of procoagulant responses by EC, including the secretion of stored vWF. We postulated that other inflammatory mediators might act to balance this procoagulant reaction, thereby assisting in the maintenance of blood fluidity during immune activation. Both gamma-interferon (gamma-IFN) and tumor necrosis factor (TNF) were found to act independently and cooperatively to depress the stimulated release of vWF from EC. Analysis of stored vWF in either gamma-IFN and/or TNF-treated EC demonstrated a loss of high molecular weight multimers while immunofluorescent studies documented a loss of visible Weibel-Palade bodies. This suggests that gamma-IFN and TNF interfere with normal vWF storage. gamma-IFN acted in a dose-, time-, and RNA-dependent fashion, and its inhibition of vWF release was reversible with time. No effect of gamma IFN on EC was noted when anti-serum to gamma-IFN was added. Unlike gamma-IFN, alpha-interferon did not effect EC vWF. Therefore, gamma-IFN and TNF may be important in decreasing vWF release during inflammatory or immunologic episodes. PMID- 2112032 TI - Monoclonality in B-lymphoproliferative disorders detected at the DNA level. AB - A new method was developed for detection of monoclonality at the DNA level in B lymphoproliferative disease using the polymerase chain reaction and consensus primers for the V and J regions of the immunoglobulin gene. Monoclonality was detected in DNA from 15 of 15 clonal B-lymphoblastoid cell lines and from 19 of 23 cases of B-lymphocyte neoplasia, but not from any of 16 normal T-lymphocyte clones, 9 cases of T-lymphocyte neoplasia, 20 samples of polyclonal peripheral blood lymphocytes, and 8 cases of reactive lymphadenopathy. This method for detection of monoclonality is likely to be of routine value in diagnosis owing to its simplicity, speed, and versatility. PMID- 2112033 TI - Reconstitution of cell-free NADPH-oxidase from human monocytes and comparison with neutrophils. AB - A rapid centrifugal elutriation procedure was developed to prepare high amounts of pure human blood monocytes. After disruption by nitrogen cavitation, a cytosol and a membrane fraction were obtained by sucrose-Percoll density centrifugation. The plasma membrane fraction contained cytochrome b558 and was free of microsomal or mitochondrial cytochromes as determined by low-temperature absorbance spectroscopy. Cell-free NADPH-oxidase activity from monocytes and neutrophils was reconstituted with cytosol and membranes in the presence of sodium dodecyl sulphate. By comparison with neutrophils, the cell-free NADPH-oxidase from monocytes showed a two- to threefold lower specific activity. The NADPH-oxidase was reconstituted with neutrophil membranes and monocyte cytosol, and vice versa. The Km for NADPH was always lower when monocyte cytosol was used. These experiments indicate that the membrane-bound components of the NADPH-oxidase from neutrophils and monocyte are similar and that levels of NADPH-oxidase components in the cytosols differ. Interferon gamma-treatment of the monocytes had no effect on the specific activity of the cell-free NADPH-oxidase. PMID- 2112034 TI - Comparative analysis by two-dimensional iodopeptide mapping of the RhD protein and LW glycoprotein. AB - The RhD polypeptide and LW glycoprotein were separately immunopurified with monoclonal antibodies and compared by two-dimensional (2-D) iodopeptide mapping after digestion with alpha-chymotrypsin. These proteins have distinct 2-D maps, as seen after 125I-labeling tyrosine residues (chloramine-T procedure), and even more strikingly after labeling primary amine residues (Bolton-Hunter procedure). Of the more than 20 iodopeptides visualized, only five migrated identically when preparations of RhD and LW were directly compared, suggesting that RhD and LW are different proteins that may share some common protein domains. N-glycanase treatment of the iodopeptides did not modify the 2-D map of the RhD protein but greatly affected the LW map, further indicating that LW, but not RhD, carries N linked carbohydrate chains. After deglycosylation the LW map was different from the RhD map, confirming that the RhD and LW polypeptides are different proteins. These findings demonstrate that LW is neither a glycosylated form of Rh protein nor is Rh a precursor of LW. PMID- 2112035 TI - Lipid lowering drugs. PMID- 2112036 TI - Clinical study of relative biological effectiveness for cervical carcinoma treated by 252Cf neutrons and assessed by histological tumour eradication. AB - Clinical data of the University of Kentucky trial using californium (252Cf), or caesium (137Cs), are reviewed for dose-response based on the endpoint of tumour eradication estimated from hysterectomy specimens obtained 4-6 weeks after preoperative irradiation. These data are used to assess the relative biological effectiveness (RBE) for 252Cf neutrons compared with 137Cs gamma radiation. Tumours treated were of common stage but were of bulky or barrel shape suitable for "radiosurgical" therapy. Dose-response curves were constructed, and additional data from the literature used to analyse the curve shape. The photon dose-response curve is complex on a logarithmic plot, whereas the 252Cf neutron curve is exponential. This indicates that the RBE can be different depending on the number of implants, schedule and size of dose delivered per session. The RBE values were approximately 8.0 at low doses or for multiple implants but they may rise to approximately 16 at larger doses or for single 252Cf implants. PMID- 2112037 TI - The effect of secondary electron spread on the penumbra in high energy photon beam therapy. AB - In photon beam therapy, the geometric penumbra width is determined by the source size and the collimator design. The width of the physical (i.e. dosimetric) penumbra involves an additional contribution from secondary electron spread. Using a suitably defined measure of penumbra width, the separate widths due to photons and secondary electrons are additive in quadrature. Secondary electron spread functions were measured using photographic dosimetry for 60Co gamma rays and for 4, 8 and 16 MV X rays. The results suggest that, under typical treatment conditions, secondary electron spread may be the predominant contributor to the penumbra at effective generating voltages exceeding 10 MV. The implications for selection of beam energy in precision small-field radiotherapy are discussed briefly. PMID- 2112038 TI - Intermittent lithium therapy in a bipolar patient. AB - A 35 year old married male who had previously had manic episodes twice, during winter months, was treated with intermittent lithium therapy between November and February of each year and was well for a period of five years. The case report and the findings are discussed to demonstrate the possibility of intermittent lithium therapy in some patients. PMID- 2112039 TI - Interstitial pneumonitis associated with ifosfamide therapy. AB - Ifosfamide and cyclophosphamide have many toxicities in common. Interstitial pneumonitis has not been reported previously as a side effect of ifosfamide therapy. The authors report the case of a 58-year-old woman who was treated with ifosfamide for soft tissue sarcoma. After the fifth cycle of chemotherapy she developed clinical evidence of interstitial pneumonitis, a diagnosis that was later confirmed at autopsy. The authors suggest that ifosfamide therapy was directly related to this patient's fatal case of interstitial pneumonitis. PMID- 2112040 TI - 7-Beta-D-galactopyranosyloxycoumarin-4-acetic acid and its methyl ester as substrates for the beta-D-galactosidase of Escherichia coli. PMID- 2112041 TI - Effects of chronic glyceryl trinitrate on left ventricular haemodynamics in a rat model of congestive heart failure: demonstration of a simple animal model for the study of in vivo nitrate tolerance. AB - STUDY OBJECTIVE: The aim of the study was to investigate the problem of pharmacological tolerance to nitrate therapy in congestive heart failure, using an animal model. DESIGN: The effects of chronic glyceryl trinitrate infusions were studied in a rat model of congestive heart failure, induced by myocardial infarction, wherein surgical procedures have been developed to permit continuous monitoring of ventricular pressures in conscious animals for up to 4-5 d. SUBJECTS: male Sprague-Dawley rats were used, weight 300-325 g, n = 3-7 per experiment. MEASUREMENTS AND MAIN RESULTS: Glyceryl trinitrate infusion (18 micrograms.kg-1.min-1) in rats with congestive heart failure caused by a 28.5(SEM 3.5)% infarction induced a rapid fall in left ventricular end diastolic pressure from 12.0(0.8) mm Hg to a peak effect of 5.5(0.6) mm Hg within 30 min (n = 7), but rapid attenuation developed beginning about 4 h after the start of the infusion. Complete abolition of the haemodynamic effects of glyceryl trinitrate was observed after 8 h of infusion. After a 12 h wash out period, responsiveness to a new infusion of glyceryl trinitrate (same dose) was restored. Withdrawal of nitrovasodilator dose led to rapid return to baseline left ventricular end diastolic pressure values. Infusion of vehicle to control animals (infarct size not different from treatment group) caused no haemodynamic effects. CONCLUSIONS: The haemodynamic changes caused by glyceryl trinitrate resemble those seen in man and suggest a possible use for this animal model in examining the mechanisms of nitrate action and tolerance. PMID- 2112042 TI - Cellular electrophysiological effects of flecainide on human atrial fibres. AB - STUDY OBJECTIVE: The aim of the study was to examine the electrophysiological characteristics of human atrial specimens collected during heart surgery and to investigate the effects of the class I antiarrhythmic agent flecainide on their electrical activity. DESIGN: Atrial specimens were studied using standard microelectrode techniques, with and without superfused flecainide (5 x 10(-7) M) or the transient outward current inhibitor 4-aminopyridine (0.5 mM). EXPERIMENTAL MATERIAL: Atrial fragments 0.5-1.0 cm2 were obtained at operation from 34 patients, mean age 30 years. There was no history of previous atrial arrhythmia in any patient and drug therapy was stopped 24 h before surgery. MEASUREMENTS AND MAIN RESULTS: Two types of transmembrane action potential were identified: (1) triangular shaped potentials (group A, classically found in animal models); (2) potentials with a large plateau preceded by a notch (group B). The effect of flecainide was compared on the the two types of action potential. In both, flecainide lessened the depolarisation rate. In group B, but not in group A, it increased the action potential duration at 50% and 90% repolarisation (APD50, APD90) and the effective refractory period. The notch in group B action potentials is generated by transient outward currents (Ito). Inhibition of these currents, either by increasing the pacing rate or by adding 4-aminopyridine, limited the increase in APD50, APD90, and effective refractory period generated by the presence of flecainide. CONCLUSIONS: The effects of flecainide on the atrial repolarisation process depend on the shape of the action potential. These effects are more marked in cells with a plateau, where Ito is activated. PMID- 2112043 TI - Sympathectomy alters acetylcholinesterase expression in adult rat heart. AB - STUDY OBJECTIVE: The aim of the study was to determine the significance of adrenergic nerve associated acetylcholinesterase for the pool of total acetylcholinesterase molecules. DESIGN: Acetylcholinesterase was analysed after destruction of adrenergic nerves by 6-hydroxydopamine or bilateral stellate sympathectomy. Effectiveness of treatment was verified by determining noradrenaline concentrations in right ventricle. Acetylcholinesterase activity was assayed in homogenates of atria and portions of left ventricular free wall. SUBJECTS: Adult male Sprague-Dawley rats were used, weight 225-260 g, n = 5 per experimental group. MAIN RESULTS: Sympathectomy caused a small decrease in acetylcholinesterase activity, due to a decrease in the activity of the tetrameric globular form of the enzyme. Choline acetylcholinesterase activity was not altered by sympathectomy, which is an indication that cholinergic nerves were not affected. CONCLUSIONS: The contribution of adrenergic neurones to the cardiac pool of acetylcholinesterase is measurable and consists primarily of the tetrameric globular form of the enzyme. PMID- 2112044 TI - Meningococcal disease, 1983-1989, British Columbia. PMID- 2112045 TI - Detection of DNA strand breaks in Escherichia coli treated with platinum(IV) antitumor compounds. AB - DNA strand breaks were observed in bacteria treated with Pt(IV) but not Pt(II) antitumor compounds by two methods. First, compounds which cause DNA strand breaks produced an SOS induction signal which was detected by a rapid bacterial assay. In addition, the capacity of these compounds to cut DNA in vivo was directly measured by agarose gel electrophoresis of pBR322 DNA extracted from bacteria treated with these drugs. cis-Diamminetetrachloroplatinum(IV) (cis-DTP) and cis-dichloro-trans-dihydroxo-cis-bis(isopropylamine)-platinum(IV) (iproplatin) produced strand breaks in both assays while cis diamminedichloroplatinum(II) (cisplatin) did not. These results indicate that Pt(IV) antitumor complexes may cause DNA damage in vivo which is not produced by Pt(II) compounds. PMID- 2112046 TI - Specificity of human natural antibody to recombinant tissue-type plasminogen activator (t-PA) expressed in mouse C127 cells. AB - A natural antibody with binding specificity for recombinant tissue-type plasminogen activator (t-PA) expressed in mouse C127 cells was present in almost all disease-free humans and patients with thrombotic disease examined. This antibody was specific for a carbohydrate, alpha 1-3-linked galactose residue, and was isolated by affinity chromatography using Synsorb 90 coupled with the glycosidic epitope Gal alpha 1-3Gal beta 1-4Glc-R as an immunoadsorbent. The evaluation of various glycoproteins for ability to bind the purified antibody in ELISA demonstrated that not only recombinant t-PA from C127 cells but also recombinant erythropoietin (EPO) and recombinant protein C produced in C127 cells have alpha 1-3-linked galactose residues on their sugar side chains. This anti alpha-galactosyl antibody also interacted with natural t-PA from human vascular trees (vascular t-PA) and placenta (placenta t-PA), but not to melanoma t-PA, recombinant t-PA, EPO or protein C expressed in Chinese hamster ovary (CHO) cells. PMID- 2112047 TI - Quantitation of hyaluronic acid and chondroitin sulphates in rabbit synovial fluid by high-performance liquid chromatography of oligosaccharides enzymatically derived thereof. AB - A high-performance liquid chromatographic (HPLC) method for quantifying unsaturated hexasaccharide and tetrasaccharide from Streptomyces hyaluronidase enzyme digestion products of hyaluronic acid was developed using a gel-permeation column packed with a sulphated polystyrene-divinylbenzene gel. For the oligosaccharides, the separation was accomplished in less than 7 min with a detection limit of 65 ng. An unsaturated non-sulphated disaccharide prepared from hyaluronic acid (delta Di-HA) and an unsaturated sulphated disaccharide (delta Di 4S) were analyzed by a HPLC method using a combination of two different gel permeation columns. The separation of the disaccharides required less than 17 min at a flow rate of 0.7 ml/min with detection limits of as little as 4 ng for delta Di-HA and 5 ng for delta Di-4S. Both chromatographic methods were used for assay of a major component of hyaluronic acid and trace amounts of chondroitin sulphates in rabbit synovial fluid. The resulting contents of hyaluronic acid were compared to the values of polymeric hyaluronic acid directly measured by a HPLC method using two gel-permeation columns packed with a poly(hydroxyalkyl methacrylate) gel and the amounts of hyaluronic acid converted from uronic acid content determined by a colorimetric method. PMID- 2112048 TI - Inhibitory effects of flavonol glycosides on 12-O-tetradecanoylphorbol-13-acetate induced tumor promotion. AB - The two-stage carcinogenesis by 7,12-dimethylbenz[a]anthracene and 12-O tetradecanoylphorbol-13-acetate (TPA) in mice was inhibited by kaempferol and flavonol glycosides, whereas naringenin, a flavanone, had no effect. The induction of epidermal ornithine decarboxylase activity by TPA was also inhibited by kaempferol, whereas mauritianin, a kaempferol glycoside, failed to inhibit it. In addition, the effect of the flavonol glycosides on cell-mediated immunosuppression in the two-stage carcinogenesis, observed in terms of initiation after 14 weeks, was antagonized by mauritianin and myricitrin. Cell mediated immunosuppression in the two-stage carcinogenesis was unaffected by kaempferol and naringenin. These results suggest that the inhibitory effects of flavonol glycosides may have been at least partly due to activation of immune responses against tumors. PMID- 2112049 TI - An autolytic substance in a freshwater cyanobacterium Phormidium tenue. AB - An autolytic substance in an axenic cyanobacterium, Phormidium tenue, was identified as a mixture of fatty acids, by use of cultured cells in the laboratory. Among them, linoleic acid and linolenic acid were potent growth inhibitors. PMID- 2112050 TI - Nomenclature for synthetic peptides representative of immunoglobulin chain sequences. WHO-IUIS Nomenclature Sub-Committee. AB - The source (species of origin), type, and subgroup (where applicable) of the immunoglobulin chain are indicated prior to the numbers of the first and last amino acid residues comprising the synthesized sequence (stated in parentheses), e.g., human gamma 1 (289-298) or rat epsilon (143-147). Square brackets indicate that the peptide is an analogue; substituted amino acids are identified by the three-letter code; superscripted numbers indicating the residue at which the substitution, removal or addition occurs. Further substitutions are specified within round brackets. For example, human gamma 1 (289-298) [D-Thr298] and human gamma 1 (289-298) [Asn (CHO)297]. PMID- 2112051 TI - Comparative studies on the action of 7-N-[2-[[2-(gamma-L glutamylamino)ethyl]dithio]ethyl]mitomycin C and of mitomycin C on cultured HL-60 cells and isolated phage and plasmid DNA. AB - The mechanism of action of a new mitomycin C (MMC) derivative, KT6149, was studied in human leukemia HL-60 cells and in isolated phage and plasmid DNA, and its effects were compared with those of MMC. Cell growth was markedly inhibited by KT6149, with an IC50 of 2 x 10(-9) M, that for MMC being 2 x 10(-8) M. DNA synthesis of HL-60 cells as determined by incorporation of [3H]-thymidine was also inhibited by KT6149, with an IC50 of 2 x 10(-7) M as compared with 2 x 10( 6) M for MMC. RNA and protein synthesis were less markedly inhibited at low concentrations. Alkaline sucrose density-gradient centrifugation revealed a significant decrease in sedimentation velocity for cellular DNA of the cells after 1 h treatment with KT6149 at concentrations higher than 10(-7) M. In contrast, no such change was observed for DNA of cells treated with MMC, even at a concentration of 10(-5) M. In a cell-free system, analysis by agarose gel electrophoresis patterns showed that the drug induced a decrease in the amount of covalently closed circular DNA of phage PM2 and an increase in that of open circular DNA in the presence of dithiothreitol (DTT), whereas MMC did not cause any change in DNA subfraction amounts. Furthermore, the electrophoretic mobility of linearized pBR322 DNA in alkaline agarose gel was significantly decreased by KT6149 in the presence of DTT and FeSO4, no such change being observed in the case of MMC. The results clearly indicate that the inhibitory effects of KT6149 on the growth and DNA synthesis of HL-60 cells are more potent than those of MMC and that KT6149-induced DNA damage is due to single-strand scission and to cross linking of DNA, suggesting a mode of activation different from that of MMC. PMID- 2112052 TI - Ifosfamide and mesna at high doses for the treatment of cancer of the cervix: a GETLAC study. AB - This study was carried out to assess the efficacy of high-dose ifosfamide/mesna (HDIFM) in the treatment of advanced or recurrent cancer of the cervix. In all, 18/21 evaluable patients with advanced or inoperable cervical cancer were included. The mean age was 42 years (range, 31-58 years); and the International Federation of Gynecology and Obstetrics (FIGO) stage was III in 10 patients and IV in 11. The Karnofsky performance status ranged between 70 and 90, with a median of 77. Ten patients had previously been treated with surgery, radium and cobalt (8) or cobalt alone (2). Therapy consisted of 3.5 g/m2, ifosfamide (IFO) given in an 8-h i.v. infusion on days 1-5 and mesna at 20% of the IFO dose, given i.v. at 0, 2, 4, 6 and 8 h, followed by mesna at 40% of the IFO dose by the oral route at 10 and 12 h on days 1-5. For evaluation purposes, patients received at least two cycles. Toxicity was registered in 137 cycles and was mild to moderate. Three complete (16.6%) and six partial (33.3%) responses were observed (50%), but 66% of them occurred in areas that had not previously been irradiated. The median duration of response was 14 months and the overall median survival was 15+ months (18+ months for responders). The Karnofsky scale after treatment ranged from 90 to 100. The results of this study indicate that HDIFM is well tolerated, giving a high percentage of remission (50%) and significantly improving the quality of life. PMID- 2112053 TI - Ifosfamide given as a 24-h infusion with mesna in patients with recurrent ovarian cancer: preliminary results. AB - The continuous 24-h infusion of ifosfamide (IFX) with mesna was studied in 44 patients with therapy-resistant or relapsing ovarian cancer. All patients had stage III disease and had been pretreated with at least one combination comprising an alkylating agent and a cisplatin analogue (22, with one combination; 16, with two; and 6, with three or more). The median number of IFX cycles received was two. Of 40 evaluable patients, 2 achieved a complete response, 5 showed a partial response and 6 had stable disease. A total of 27 patients had tumor progression after one or two treatment cycles. All seven responders had responded to previous treatment for a median duration of 5 months (range, 5-41 months). No patients who progressed during alkylating-agent treatment responded to IFX given subsequently. The median progression-free period was 6 months (range, 4-12 months), and the median overall survival was only 6 months, indicating the advanced stage of disease in these patients. The median overall survival in progressive patients was 5 months (range 2-13+ months) and that in the remaining group was 13 months (ranges 3(+)-24 months) (P less than 0.05). This treatment was moderately well tolerated. Grade 3 nausea and vomiting occurred in 27% of cycles and grade 3-4 leukopenia was observed in 47%, but thrombocytopenia was hardly ever found. In eight patients there was a deterioration of renal function. Among a total of 131 cycles, the dose was reduced for only 9 due to myelotoxicity and for 3 due to nephrotoxicity. IFX seems to be active only in patients who have relapsed after responding to previous cytotoxic treatment. PMID- 2112054 TI - Early phase II Gynecologic Oncology Group experience with ifosfamide/mesna in gynecologic malignancies. AB - Starting in July 1985, the Gynecologic Oncology Group conducted a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received 1.5 g/m2 i.v. ifosfamide daily for 5 days. Mesna was given i.v. q4h x 3 following ifosfamide; each dose was 20% of the daily ifosfamide dose. All patients with ovarian and 87% of those with cervical cancer had previously undergone platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2 daily in all patients who had received prior chemo- or radiotherapy. In epithelial ovarian carcinoma, responses were observed in 8 (20.0%) of 41 evaluable patients, with 3 (7.0%) complete responses. Response duration was 2.1-20.3+ months, with a median of 6.9+ months. In squamous-cell carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients showed partial responses of 1.8, 2.2, and 3.1 months' duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) achieved complete and 3 (11.5%) showed partial responses, for an overall response rate of 30.7%. Response duration was 1.4(+)-8.6 months, with a median of 3.8 months. Toxicity included two deaths due to renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies. PMID- 2112055 TI - Experience of the Belgian Society of Medical Oncology with single-administration 5 g/m2 ifosfamide with mesna as second- or third-line therapy in advanced breast cancer. AB - In an ongoing phase II trial conducted in advanced breast cancer, we tested a therapy schedule consisting of continuous, 24-h infusion of 5 g/m2 ifosfamide (IFO) in 3 1 dextrose saline with mesna (MSN), repeated every 3 weeks until disease progression. Since September 1988, 16 heavily pretreated patients with advanced disease (11 with visceral lesions) considered refractory to standard chemotherapy (regimens always including cyclophosphamide) have been included. Objective partial remissions were observed in two cases (one in liver and one in soft-tissue and pleural lesions), and disease stabilization for at least 3 months occurred in four cases. No treatment-related death was recorded and tolerance was judged to be excellent (six cases) or acceptable in all instances. The haematological toxicity consisted mainly of transient leucopenia (nadirs evaluated by WHO scale as grade 3 in 43% and grade 4 in 29%), sometimes associated with thrombocytopenia (grade 3 in 7% and grade 4 in 7%). Other side effects included nausea and/or vomiting (grade 3-4 in 33%); worsening of preexisting alopecia (five cases); haemorrhagic cystitis (one case); mild, transient somnolence (two cases); and moderate fluid retention (two cases). We concluded that infusion of 5 g/m2 IFO over 24 h with MSN rescue might represent an acceptable second- or third-line salvage regimen. Close monitoring of haematological and renal function parameters is recommended. A larger number of patients will be treated in a continuation of this study to evaluate the true response rate within narrower confidence limits. PMID- 2112056 TI - Ifosfamide/etoposide and mesna uroprotection in advanced breast cancer. AB - The object of the study was to evaluate the effectiveness of ifosfamide/etoposide and mesna therapy in advanced breast cancer. A total of 44 patients with breast cancer were included in the trial. Eligibility criteria included measurable, refractory disease; prior anthracycline therapy (or its contraindication); a life expectancy of at least 3 months; and adequate hepatic, renal, CNS and bone marrow function. All patients were less than or equal to 70 years of age and had a Karnofsky performance status of greater than or equal to 50%. There were 36 evaluable cases. Sites of metastatic disease included bone (19), skin (18), liver (9), lung (14), lymph node (19), and miscellaneous (7). Treatment consisted of 1,500 mg/m2 ifosfamide given i.v. on days 1-5, 120 mg/m2 etoposide given i.v. on days 1-3, and 400 mg i.v. mesna given with and at 4 and 8 h after ifosfamide. Cycles were repeated every 28 days. Initial doses were reduced by 25% or 50% in patients who had previously undergone both chemotherapy and radiotherapy. A median of 4 cycles (range, 2-8) were given. The myelotoxicity was marked: WHO grades 3/4 leukopenia (n = 37), grades 3/4 thrombocytopenia (n = 12), and grades 2/3 anemia (n = 13). Due to myelotoxicity, dose reduction or prolongation of treatment-free intervals was necessary in 28 cases. Alopecia was seen in 35 patients and CNS toxicity, in 8. Partial remission (PR) was obtained in five cases and complete remission (CR), in three. Sites of response included the lung (5), skin (4), lymph node (5), and peritoneum (1). The duration of response was 4 (n = 2) and 8 (n = 1) months for CR and 2 (n = 2), 6 (n = 2), and 10 (n = 1) months for PR. We conclude that the ifosfamide/etoposide and mesna regimen is effective, but its myelotoxicity is treatment-limiting. PMID- 2112057 TI - High-dose ifosfamide and mesna in advanced breast cancer. A phase II study. AB - Thirty-two patients with metastatic breast cancer had previously been treated with chemotherapy (including anthracyclines). They were included in a trial to receive 6 g/m3 ifosfamide, mixed with 6 g/m2 mesna in 1000 ml saline infusion, infused over 4 h. Therapy was repeated every 21 days; the dose was reduced by 50%. Twenty-eight patients could be evaluated. An average of 4.2 cycles (range 2 8) was applied. One patient (4%) showed complete remission. Ten patients (36%) had a partial response. Ten patients (36%) experienced SD and the remaining patients (25%) PD. We conclude that high-dose ifosfamide shows activity in this group of pretreated patients and merits further investigation. PMID- 2112058 TI - Transplacental transfer of aflatoxin in humans. AB - This study quantified aflatoxin (AFB1, AFG1 and AFQ1) by enzyme-linked immunosorbent assay in human cord sera obtained at birth and in serum obtained immediately after birth from the mother. The subjects of the study were residents of Songkhla, Thailand. Of the 35 samples of cord sera, 17 (48%) contained aflatoxin in concentrations from 0.064 to 13.6, mean 3.1 nmol/ml. By comparison only two (6%) of 35 maternal sera contained aflatoxin (mean 0.62 nmol/ml). These results demonstrate transplacental transfer and concentration of aflatoxin by the feto-placental unit which may be of biological importance. Aflatoxins are mutagenic, carcinogenic and teratogenic and cause immunosuppression in animals. The implications of these findings are potentially profound and deserve further study. PMID- 2112059 TI - Effects of cigarette smoke condensate and 12-O-tetradecanoylphorbol-13-acetate on gap junction structure and function in cultured cells. AB - The effects of cigarette smoke condensate (CSC) and the phorbol ester 12-O tetradecanoylphorbol-13-acetate (TPA) on gap junction structure, quantity and function were investigated. Gap junction morphology was studied in rotary shadowed freeze-fracture replicas of primary chick embryo hepatocytes. CSC (24 micrograms/ml) induced a strong decrease of gap junction areas; within 6 h the areas were reduced by greater than 60%. In the first 3 h of exposure, TPA (100 ng/ml) also reduced gap junction areas, but in the next 3 h a partial recovery was observed. Protoplasmic fracture face centre-to-centre particle spacings were used as a measure for gap junction coupling. CSC had a slow (although not significant) reducing effect on particle spacings, while TPA induced a reduction from 10.6 nm (control) to 10.0 nm within 3 h, indicating a reduction of coupling. Gap junctions were quantified in thin sections of cultured chick embryo hepatocytes, V79 fibroblasts, and co-cultivated hepatocytes and V79 cells. CSC did not influence gap junction numbers in any of these cultures, while TPA treatment caused a disappearance of gap junctions between hepatocytes and between hepatocytes and V79 cells in the first 12 h of cultivation. In the following 36 h a slow recovery could be observed. Gap junctions between V79 cells had already disappeared within 30 min. Metabolic co-operation between hepatocytes and hypoxanthine-guanine phosphoribosyltransferase-deficient V79 cells was quickly and continuously blocked by CSC over 27 h, whereas the phorbol ester induced a transient block. The dissimilar effects of these compounds on both gap junction structure and function indicate that they act via different mechanisms. The finding that CSC did not inhibit phorbol ester protein kinase C binding and did not activate this protein kinase in vitro supports this hypothesis. PMID- 2112060 TI - Effects on intercellular communication in human keratinocytes and liver-derived cells of polychlorinated biphenyl congeners with differing in vivo promotion activities. AB - Several purified polychlorinated biphenyl (PCB) congeners with differing toxicity/tumor promotional activities in rat liver in vivo were tested for their effects on gap-junctional intercellular communication (GJIC) in cell strains and lines derived from human liver and skin. This in vitro assay is being developed to detect various classes of tumor promoters. The 3-methylcholanthrene (MCA)-type cytochrome P450 inducer and hepatotoxic promoter 3,3',4,4'-tetrachlorobiphenyl was inactive in this assay for all of the cells tested, suggesting this promoter acts by other mechanisms. The phenobarbital-like enzyme inducer and less toxic promoter 2,2',4,4',5,5'-hexachlorobiphenyl inhibited GJIC in both liver and skin cells, whereas the 2,2',5,5'-tetrachlorobiphenyl congener, which does not act as a promoter in rat liver, inhibited GJIC only in the skin cell types and in one of the liver cell strains thought to be of bile duct origin. 2,3,4,4',5 Pentachlorobiphenyl, a mixed (phenobarbital plus MCA) inducer of cytochrome P450, inhibited GJIC in both liver and skin cells, suggesting that it may be a promoter in vivo. The results suggest that GJIC inhibition is a property of PCB congeners with phenobarbital-like enzyme induction capabilities, and that there exist some tissue/cell type differences in sensitivity to these congeners. PMID- 2112061 TI - Glutathione S-transferase localization in aflatoxin B1-treated rat livers. AB - Overexpression of detoxication enzymes is associated with the development of drug resistant, preneoplastic nodules in the carcinogen-treated rat liver. The most consistent marker of preneoplasia in many experimental models is increased expression of the pi-class glutathione S-transferase (GST) YfYf. We have confirmed by immunostaining that the pi-class GST is overexpressed in aflatoxin B1-induced preneoplastic nodules and liver tumours in rats. However, pi-class GST YfYf has low activity against aflatoxin B1-8,9-epoxide, and most activity against this cytotoxic and genotoxic metabolite is associated with the alpha-class GSTs YaYa, YaYc and YcYc. We have demonstrated that there is also a consistent increase in the alpha-class GSTs in this model. It seems likely that the overexpression of the Ya and Yc subunits, rather than increased levels of the pi class GST YfYf, is responsible for the acquisition of a drug-resistant phenotype in rat liver preneoplastic nodules and tumours induced by aflatoxin B1. PMID- 2112062 TI - Effects of antihistamines on phorbol ester tumor promotion and vascular permeability changes. AB - Substantial evidence suggests that inflammation is an essential component of the phorbol ester tumor promotion stage of multistage carcinogenesis in mouse skin. In order to understand better the significance of this relationship, studies were directed at identifying the principal mediators of the vascular permeability component of inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Antihistamines and inhibitors of arachidonic acid metabolism were compared with respect to their anti-inflammatory activity and the correlation of this parameter with their effect on tumor promotion. The H1 histamine receptor antagonist, diphenhydramine, suppressed TPA-induced vascular leakage by 25 and 50% at topical doses of 0.342 mumol (100 micrograms) and 0.856 mumol (250 micrograms) respectively. In initiated mice, these same doses inhibited papilloma development by 40 and 75%. Inhibition of tumors was also observed when diphenhydramine was given orally. The H2 antagonist, cimetidine, which could only be supplied orally, had little effect on either TPA-induced vascular permeability or promotion. The lipoxygenase inhibitor nordihydroguaiaretic acid also suppressed vascular permeability and has been reported to inhibit papilloma development. The cyclooxygenase inhibitor indomethacin, however, has no effect on TPA-induced vascular permeability. Collectively, these data suggest that the increased vascular leakage observed with TPA contributes to tumor development and that this event is mediated by both the H1 histamine receptors and one or more of the lipoxygenase products of arachidonic acid. PMID- 2112063 TI - A comparison of diagnostic tests for keratoconjunctivitis sicca: lactoplate, Schirmer, and tear osmolarity. AB - We compared diagnostic tests for keratoconjunctivitis sicca (KCS) in previously diagnosed patients and normal controls to determine the incidence of true negatives (specificity) and true positives (sensitivity). Tear osmolarity testing, the Schirmer filter paper test, and lactoferrin determination by the Lactoplate radial immunodiffusion (RID) method were performed in 20 KCS patients diagnosed on the basis of presenting symptoms and clinical examination. Similar determinations were performed in 20 age- and sex-matched normal control subjects. Mean lactoferrin concentrations in the right eyes of the KCS patients and normal controls were 134 +/- 78 (+/- 1 SD) mg/dL and 118 +/- 56 mg/dL, respectively. Tear osmolarity was 323 +/- 12 mosm/L and 306 +/- 7 mosm/L, in KCS patients and normal controls, respectively. The Schirmer test yielded a mean of 2.4 +/- 1.8 mm/minute of wetting in the KCS patients and 3.0 +/- 1.4 mm/minute in the controls. Used as a diagnostic test, lactoferrin determination by RID was found to have 35% sensitivity and 70% specificity; tear osmolarity determination had 90% sensitivity and 95% specificity; and the Schirmer test yielded 25% sensitivity and 90% specificity. PMID- 2112064 TI - The effects of ophthalmic solutions on the transmission of light through hydrogel lenses. AB - We incubated ten different hydrogel lens materials in nine different artificial tear preparations and in cromolyn sodium (Opticrom) 4% at 35 degrees C for a period of 6 months. The subsequent ability of these hydrogel materials to transmit visible light was analyzed spectrophotometrically as a measure of each solution's compatibility with the different hydrogel materials. Ultra Tears solution was found to be significantly incompatible with four of the hydrogel materials: tetrafilcon A, deltafilcon A, phemfilcon A, and polymacon. Seven other solution/hydrogel combinations had relatively high absorbance readings that were not statistically significant. These combinations should probably be avoided. Cromolyn sodium 4% was found to be compatible with all hydrogel lens materials tested, as were the majority of artificial tear solution/hydrogel combinations. We believe that the use of the compatible solution/hydrogel combinations should produce no alteration in the ability of the hydrogel lens to transmit visible light (400-700 nm). PMID- 2112065 TI - A simple serum galactosyltransferase assay method suitable for routine use. AB - UDP-Galactose: N-acetylglucosaminyl glycoprotein beta 1-4 galactosyltransferase (GT) catalyzes the transfer of galactose to N-acetylglucosamine from UDP-[3H]Gal. The uncharged reaction product (tritiated N-acetyllactosamine) is separated from the unreacted UDP-[3H]Gal by ion-exchange chromatography. The major advantage of this method is its rapidity compared to other isotopic techniques. PMID- 2112066 TI - Hilus cell pathology and hirsutism. AB - Hilus cell abnormalities are uncommon causes of hirsutism with virilization. Although hilus cell tumours have been well described, hilus cell hyperplasia is rare and is poorly defined clinically. We describe three cases of hilus cell hyperplasia and compare them with a case of hilus cell tumour. Both pathologies were associated with increased testosterone and oestradiol secretion. Suppression of testosterone to the 'normal range' in response to exogenous oestrogen was seen only in the cases with hyperplasia; only partial responsiveness was seen in the case with hilus cell tumour. Bilateral oophorectomy offers the potential for cure for both hilus cell hyperplasia and tumour. PMID- 2112067 TI - Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: an analysis of 263 consecutive cases. AB - Two hundred and sixty-three women with ultrasound-diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI greater than 25 kg/m2). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non-obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5 alpha-reductase activity, were higher in obese than in non-obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8-h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio-availability of androgens to peripheral tissues and enhanced activity of 5 alpha-reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained. PMID- 2112068 TI - Bioactive and immunoreactive FSH in serum of normal and oligospermic men. AB - In men suffering from idiopathic oligospermia and azoospermia the hypothesis was tested that decreased spermatozoa production could be due in part to inadequate hormonal stimulation of spermatogenesis. In 53 healthy male subjects with normal spermatozoa production (n = 10), varying degrees of oligospermia (n = 40), and azoospermia (n = 3), serum immunoreactive LH, testosterone (T), and oestradiol (E2), and immunoreactive and bioactive FSH concentrations were determined. FSH bioactivity was estimated using the rat granulosa cell aromatase bioassay. Mean LH, T, and E2 levels were similar in the control group (spermatozoa concentration greater than 40 x 10(6)/ml) compared with men exhibiting mild (10-20 x 10(6)/ml), moderate (5-10 x 10(6)/ml), or severe oligospermia (1-5 x 10(6)/ml), and in the azoospermia group. An inverse correlation was found between immunoreactive FSH levels and spermatozoa concentration (P less than 0.05), with elevated levels (twofold increase) of FSH in the combined severe oligospermia and azoospermia (P less than 0.01) groups. Moreover, augmented (P less than 0.01) bioactive FSH levels were also observed in this group of patients. The mean bioactive to immunoreactive FSH ratio was also negatively correlated with sperm counts (P less than 0.005). In addition, T/LH ratios were inversely correlated with immunoreactive (P less than 0.05) and bioactive (P less than 0.05) FSH, which may indicate that altered Leydig cell function is involved in the augmented secretion of FSH. The data presented in this study indicate that immunoreactive FSH, as measured in oligospermia and azoospermia, does not exhibit decreased bioactivity. PMID- 2112069 TI - Impaired growth hormone response to insulin-induced hypoglycaemia in obese patients: restoration blocked by ritanserin after fenfluramine administration. AB - The aim of the present study was to test whether the serotoninergic system may be involved in the well known reduced growth hormone (GH) response to insulin induced hypoglycaemia (IIH) in obese patients. Ten obese women and 10 normal weight control women underwent three IIH tests, at 14-day intervals: the first in basal conditions, the other two after randomized administration of a serotoninergic drug, fenfluramine (FF, 120 mg/day for 7 days) and FF plus ritanserin (RIT, 30 mg/day for the first 2 days and 20 mg/day on the following days). Ritanserin is a new selective 5-HT2 blocker receptor agent. Both controls and obese patients showed similar normal basal GH levels before each test and insulin administration always effectively reduced glucose levels to values lower than 2.2 mmol/l. In the controls, the expected GH increase to IIH (peak value 56 +/- 13.4 mU/l, AUC 234.4 +/- 55 mU/min/ml) was unaffected by FF administration (peak value 43 +/- 11.4; AUC 216.8 +/- 34.8). In response to the first IIH, the obese patients showed a significantly lower GH increase than in the case of the controls (peak value 21.4 +/- 4.6 mU/l, P less than 0.02; AUC 93.2 +/- 18.6, P less than 0.02). However, in comparison with the basal test, FF administration significantly (P less than 0.001) enhanced GH response to insulin hypoglycaemia (peak value 33.4 +/- 4; AUC 150 +/- 14.6), reaching values not significantly different from those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112070 TI - The hypothalamic-pituitary-adrenal axis in infantile malnutrition. AB - We studied the circadian rhythm and the response of the hypothalamic-pituitary adrenal (HPA) axis to ovine corticotrophin releasing hormone (oCRH) stimulation and dexamethasone suppression in 32 children with grade II-III marasmus. Children were studied prior to and after nutritional rehabilitation. Mean baseline plasma cortisol concentrations were elevated at admission and decreased significantly after nutritional rehabilitation. Mean +/- SEM plasma cortisol response to oCRH increased from a basal of 480 +/- 41 to a peak of 582 +/- 58 nmol/l at the time of admission, and from a basal of 234 +/- 27 to a peak of 532 +/- 41 nmol/l after caloric rehabilitation. Dexamethasone suppression in the malnourished group was associated with a decrease in the mean +/- SEM basal plasma cortisol concentration from 397 +/- 44 to 171 +/- 44 nmol/l. After caloric rehabilitation, basal cortisol levels decreased from 259 +/- 27 to 22 +/- 5 nmol/l following dexamethasone. Our results support the concept that malnutrition is associated with decreased responsiveness to oCRH and incomplete dexamethasone suppression, and that these abnormalities are restored after nutritional rehabilitation. PMID- 2112071 TI - Thyroid function in patients with myotonic dystrophy. AB - In order to investigate endocrine disturbances in patients with myotonic dystrophy (MD), 12 patients and 20 normal controls were studied. All patients were clinically euthyroid and there were no significant differences between circulating levels (mean +/- SD) of T4 (114.7 +/- 26.8 vs 129.9 +/- 28.3 nmol/l), FT4 (16.6 +/- 4.5 vs 18.4 +/- 3.8 pmol/l), T3 (1.61 +/- 0.29 vs 1.86 +/- 0.33 pmol/l), TSH (2.7 +/- 1.3 vs 2.4 +/- 1.4 mU/l), TBG (26.7 +/- 5.5 vs 27.6 +/- 4.9 mg/l), T4/T3 (84.3 +/- 18.4 vs 82.1 +/- 15.3), and FT4/FT3 (0.28 +/- 0.05 vs 0.33 +/- 0.08). Serum FT3 (4.3 +/- 1.4 pmol/l) in patients were significantly lower than those (5.3 +/- 0.9 pmol/l) in normal controls (P less than 0.02). Thyroidal 131I-uptakes (8.7 +/- 4.3%) in patients were significantly lower than those (25.8 +/- 7.4%) in controls (P less than 0.01). The mean maximal TSH responses following TRH stimulation were significantly less in patients with MD (11.4 +/- 4.5 vs 17.0 +/- 6.2 mU/l; P less than 0.02). Neither circulating thyroid microsomal nor thyroglobulin antibodies were detectable in the 11 patients tested. Serum thyroglobulin concentrations were within the normal range in all patients but one. In conclusion, it is suggested that normal levels of serum T4, T3, FT4, TSH, TBG, T4/T3 and FT4/FT3, slight but significant decrease of serum FT3, reduced TSH response to TRH and a decrease of thyroidal radioiodine uptake might be due to a slight functional failure of TSH secretion in patients with myotonic dystrophy. PMID- 2112072 TI - Contrasting effects of norepinephrine and 5-hydroxytryptamine on contractility of abdominal aorta of two kidney-two clip hypertensive rats. Effects of inhibitors of arachidonic acid metabolic enzymes. AB - This study intends to: 1) define reactivity in vessels of two kidney-two clip (2K2C) hypertensive rats (6-11 days after clipping); 2) determine the possible involvement of prostaglandins in modulating contractile vascular responses. Cumulative dose-response curves to norepinephrine (NE), 5-hydroxytryptamine (5 HT) and potassium chloride (KCl) were elicited on helical strips of abdominal aorta both in the absence and in the presence of prostacyclin synthetase (transylcypromine, TCP, 0.25mM) or cyclooxygenase (indomethacin, IND, 0.014 mM and acetylsalicylic acid, ASA, 0.20 mM) inhibitors Vessels of hypertensive animals developed significantly less tension to NE (n = 21) but higher tension and lower ED50 in response to 5-HT (n = 9) than sham control rat vessels. Force development to KCl (n = 9) was not statistically different between hypertensive and sham vessels. Vascular responses were decreased with the inhibitors, but the contrasting effects of NE and 5-HT on clip vessels were maintained. Threshold doses of PGE2 significantly reversed the effect of IND but not that of TCP on NE responses. Threshold doses of PGI2 had no significant effect on NE and 5-HT responses under TCP. The results would indicate: 1) different functional alterations for contractions to NE and 5-HT appear to have developed in vessels of 2K2C hypertensive rats; 2) PGE2 effectively contributes to modulation of NE responses in rat aorta strips; 3) these experiments suggest that prostaglandins do not play a significant role in the altered contractility of vessels in hypertensive rats. PMID- 2112073 TI - Clinical trials and decisions for thrombolytic therapy in patients with acute myocardial infarction. PMID- 2112074 TI - Anticardiolipin syndrome in childhood: a report of two cases. AB - We describe two children with an otherwise unexplained deep vein thrombosis associated with high titer anticardiolipin antibodies (ACA) of the IgG class and circulating lupus anticoagulant (LAC). One of these patients had persistent proteinuria but neither had systemic lupus erythematosus. Our observation suggests that ACA and LAC assays should be performed in children with thromboembolic disease even when no underlying autoimmune disease can be found. PMID- 2112075 TI - Bosworth fracture-dislocation of the ankle. A case report and review of the literature. AB - The Bosworth fracture-dislocation is a rare fracture-dislocation of the ankle where the proximal fibular fragment lodges behind the tibia, rendering it irreducible by routine closed manipulations. Clinically the patient's foot is in severe external rotation. This external rotation makes the initial roentgenograms difficult to interpret. Consequently, the diagnosis is often overlooked, resulting in inappropriate treatment and a disastrous outcome. If properly recognized, these injuries can be successfully treated by closed or open techniques with return of near-normal ankle function. The problem is illustrated in a case involving a 40-year-old woman, as related to a review of the literature and discussion of the treatment rationale. PMID- 2112076 TI - Massive heterotopic ossification after biceps tendon rupture and tenodesis. AB - Few complications from tenodesis of the long head of the biceps brachii have been described despite the wide variety of techniques. In a 53-year-old man, rupture of this tendon was treated by tenodesis and was complicated by heterotopic ossification that severely limited the function of the shoulder joints. Nonsurgical conservative treatment of biceps tendon ruptures may avoid the possibility of this complication. PMID- 2112077 TI - A biophysical study of posttraumatic ectopic ossification. A case report. AB - Sites of ectopic ossification (EO) due to sports injury in a long-distance runner were biopsied and analyzed. The mineral content was compared to that of normal adult bone and to paraosteoarthropathy (POA) using biophysical methods. The degree of mineralization of bone tissue (DMBT) was employed as an evaluation of maturity of calcified tissue. Fluoride and carbonate content were determined. The crystal lattice dimensions expressed by the a and c parameters, crystal size, and/or lattice perfection were obtained with x-ray diffraction. All values were near those found in nonpathologic, newly deposited human compact bone. DMBT, crystal size, and/or lattice perfection were near those observed in a 24- to 30 month-old POA. The data suggest that posttraumatic EO represents otherwise normal young bone. PMID- 2112078 TI - The electrocardiographic changes in a case of flecainide overdose. AB - Flecainide acetate is a new potent class I antiarrhythmic agent. We report serial electrocardiographic changes occurring in a case of flecainide overdose. The initial flecainide serum level was three times greater than the upper therapeutic level. The prolonged electrocardiographic time intervals (PR and QRS) decreased in correlation with falling drug levels. As the case was associated with concomitant alcohol intoxication, we speculate about the protective effect of alcohol in order to explain our patient's benign clinical course. PMID- 2112079 TI - Comparison of the clinical performance, contraceptive efficacy and acceptability of levonorgestrel-releasing IUD and Norplant-2 implants in China. AB - The levonorgestrel-releasing IUD (LNG-IUD, 20 micrograms/d) and the Norplant-2 implants were studied in a randomized comparative clinical trial with 200 women for one year. No pregnancy or expulsion occurred with the Norplant-2. In the LNG IUD group, there was one pregnancy at the 12th month of use after an unnoticed expulsion. The net cumulative pregnancy and expulsion rates of LNG-IUD were 1.0 and 3.0. The removal rate due to menstrual disturbances in both LNG-IUD and Norplant-2 groups was 3.0. The use-related discontinuation rates were 9.0 and 3.0, and the continuation rates were 90.0 and 96.0, respectively. The differences were not statistically significant. Menstrual disturbance was the main side effect. It was improved after long time use, especially in the LNG-IUD group. After one year, the percentages of women with amenorrhea were 18.9 for the LNG IUD and 8.3 for the Norplant-2. The menstrual blood loss was statistically significantly reduced in the LNG-IUD group, and blood haemoglobin concentration increased in both groups. The LNG-IUD and Norplant-2 are highly effective, safe, long-acting, and well accepted by the Chinese women. PMID- 2112080 TI - Comparative cross-over pharmacokinetic study on two types of postcoital contraceptive tablets containing levonorgestrel. AB - A pharmaceutical and pharmacokinetic study was carried out on levonorgestrel tablets from two different sources (Hungarian- and Chinese-made). Both preparations contained 0.75 mg levonorgestrel and had been shown to have similar contraceptive efficacy and side effects when used for postcoital contraception. Absorption and bioavailability of the Hungarian-made tablets were greater as evidenced by higher serum concentrations of levonorgestrel, a greater area under the concentration-time curve during the first 24 hours, and a more marked suppressive effect on SHBG levels. These differences most probably reflect differences in their pharmaceutical formulation, in particular the extent of tablet dissolution and the degree of micronisation of levonorgestrel. PMID- 2112081 TI - Cytokine networks in the regulation of inflammation and fibrosis in the lung. AB - To understand the processes regulating inflammation and fibrosis in the human lung, we characterized the effects of recombinant interleukin-1, tumor necrosis factor, and gamma interferon on fibroblast proliferation, collagen production, interleukin-1-alpha production, interleukin-1-beta production, and interleukin-6 production. These studies demonstrated the existence of complex cytokine networks by which inflammatory cells regulate fibroblast function and fibroblasts, in turn, feed back to regulate inflammatory cell function. They also demonstrated that, in this complex network, the effect of an individual cytokine varies with the state of activation of the target cell, the presence of other cytokines in the local microenvironment, and the ability of the target cell to produce bioactive autocoids such as prostaglandins. Aspects of this cytokine network are discussed and a testable hypothesis for granuloma and abscess formation is detailed. PMID- 2112082 TI - Successful use of nasal-CPAP for obstructive sleep apnea in Hunter syndrome with diffuse airway involvement. AB - A patient with Hunter syndrome and diffuse airway obstruction had daytime hypersomnolence, snoring, and alveolar hypoventilation. Polysomnography showed severe obstructive sleep apnea. In the past, all reported cases of sleep apnea in patients with mucopolysaccharidoses had been treated with tonsillectomy/adenoidectomy or tracheostomy. This patient, in whom tracheostomy would have been very difficult due to the diffuse nature of his airway involvement, was successfully treated with high pressure nasal CPAP and supplemental oxygen. PMID- 2112083 TI - [Following curative resection of colorectal cancer, portal chemotherapy especially benefits non-transfused patients]. AB - After curative resection of colorectal cancer, immediate short-term postoperative intraportal adjuvant chemotherapy reduces the relative risk of recurrence and death in the non-transfused patient significantly, when compared to transfused patients without chemotherapy. This is demonstrated in a multivariate analysis using the Cox model on a group of 469 patients who have been intraoperatively randomized to receive either intraportal chemotherapy for 7 days or no further treatment. The transfused patients with chemotherapy and those receiving neither transfusions nor chemotherapy had a relative risk of recurrence and death situated in between the two groups mentioned above, not statistically different from either of them. In the setting of this study, 7 days postoperative intraportal chemotherapy seems particularly effective in the non-transfused patients. PMID- 2112084 TI - Raising the intracellular level of inositol 1,4,5-trisphosphate changes plasma membrane ion transport in characean algae. AB - Inositol 1,4,5-trisphosphate (InsP3) was introduced into the cytoplasm of characean algae in two different ways: (i) by iontophoretic injection into cytoplasm-enriched fragments from Chara and (ii) by adding InsP3 to the permeabilization medium of locally permeabilized cells of Nitella. In both systems this operation induced a depolarization of the membrane potential, ranging from a few mV to sequences of action potentials. The effect of InsP3 on locally permeabilized Nitella cells was abolished when InsP3 was added together with 30 mM EGTA. When inositol 1,4-bisphosphate or myo-inositol were substituted for InsP3 in this system, there was no change in the membrane potential. On the other hand, increasing the free Ca2+ concentration in the permeabilization medium induced, in a similar fashion to InsP3, action potentials. Similarities between InsP3 and Ca2+ action were also observed upon injection into Chara fragments. Both injections increased an inward current. In the first few seconds after injection the current/voltage characteristics of the InsP3-induced current resembled those of the Ca2(+)-sensitive current. Subsequently, differences between the InsP3- and Ca2(+)-induced phenomena became apparent in that the InsP3 induced current continued to increase while the Ca2(+)-induced current declined, returning to the resting level. Our results suggest that these plant cells contain an InsP3 sensitive system that, under experimental conditions, is able to affect membrane transport via an increase in cytoplasmic free Ca2+. PMID- 2112085 TI - Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment. AB - The low density lipoprotein receptor-related protein (LRP) is a cell surface glycoprotein that binds and transports plasma lipoproteins enriched in apolipoprotein E. It is synthesized in the endoplasmic reticulum as a transmembrane glycosylated precursor that migrates with an apparent molecular mass of about 600 kd on SDS-polyacrylamide gels. After it reaches the Golgi complex, the protein is cleaved to generate two subunits with apparent molecular masses of approximately 515 and 85 kd respectively. The larger NH2-terminal alpha subunit lacks a membrane-spanning region. It remains attached to the membrane through noncovalent association with the smaller COOH-terminal beta-subunit. Proteolysis occurs at the sequence RHRR, which resembles the sequence RKRR at the proteolytic site in the receptors for insulin and insulin-like growth factor-1 (IGF-1), the only other cell surface receptors known to undergo proteolytic processing. Proteolysis of LRP occurs coincident with the conversion of the N linked carbohydrates to the mature endoglycosidase H-resistant, neuraminidase sensitive form. Proteolysis is prevented by brefeldin A, which blocks transport to the Golgi complex. These data raise the possibility that LRP and the receptors for insulin and IGF-1 are processed by a specific endoprotease that recognizes protein with extended basic sequences and resides in the trans-Golgi complex or in post-Golgi vesicles of the constitutive secretory pathway. PMID- 2112086 TI - Establishment of an interleukin-5-dependent subclone from an interleukin-3 dependent murine hemopoietic progenitor cell line, LyD9, and its malignant transformation by autocrine secretion of interleukin-5. AB - An interleukin-5 (IL-5)-dependent subclone, K-5, was established from an IL-3 dependent murine hemopoietic progenitor cell line by co-culturing with bone marrow stroma cells. K-5 cells were induced to differentiate into myeloid lineage cells by co-culturing with cloned PA6 stroma cells. By co-culturing with another cloned stroma cell (ST-2s10), K-5 cells gave rise to a factor-independent transformant cell line LT-5 which proliferated in an autocrine manner by secretion of IL-5 and produced tumors in nude mice. Molecular cloning of the IL-5 gene of LT-5 cells and the nucleotide sequencing of its 5' flanking region indicate that a transposition of an intracisternal A-particle (IAP) element to the 5' flanking region of the IL-5 gene is responsible for the constitutive expression of IL-5 mRNA of an aberrant size in LT-5 cells. PMID- 2112087 TI - A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. AB - NF-IL6 is a nuclear factor that specifically binds to an IL1-responsive element in the IL-6 gene. In this study the gene encoding NF-IL6 has been cloned by direct screening of a lambda gt11 library using NF-IL6 binding sequence as a ligand. The full-length cDNA encoded a 345 amino acid protein with a potential leucine zipper structure and revealed a high degree of homology to a liver specific transcriptional factor, C/EBP, at the C-terminal portion. The bacterial fusion protein bound to the CCAAT homology as well as the viral enhancer core sequences as in the case of C/EBP. Recombinant NF-IL6 activated the human IL-6 promoter in a sequence-specific manner. Southern blot analysis demonstrated the high-degree conservation of the NF-IL6 gene through evolution and the existence of several other related genes sharing the DNA-binding domain. NF-IL6 mRNA was normally not expressed, but induced by the stimulation with either LPS, IL-1 or IL-6. Interestingly, NF-IL6 was shown to bind to the regulatory regions for various acute-phase protein genes and several other cytokine genes such as TNF, IL-8 and G-CSF, implying that NF-IL6 has a role in regulation not only for the IL 6 gene but also for several other genes involved in acute-phase reaction, inflammation and hemopoiesis. PMID- 2112088 TI - The ryh1 gene in the fission yeast Schizosaccharomyces pombe encoding a GTP binding protein related to ras, rho and ypt: structure, expression and identification of its human homologue. AB - A gene, ryh1, of the fission yeast Schizosaccharomyces pombe encoding a GTP binding protein of 201 amino acids and belonging to the ras superfamily was isolated using the protein-coding region of the cloned Saccharomyces cerevisiae YPT1 gene as hybridization probe. The ryh1 gene is interrupted by three introns. ryh1 null mutants are viable but unable to grow at temperatures greater than 35.5 degrees C. Invertase of ryh1- cells is properly secreted but has a faster electrophoretic mobility compared to that of wild-type cells. The temperature sensitive phenotype of ryh1 null mutants is complemented by the human rab6 cDNA expressed either under transcriptional control of the S.pombe adh or the SV40 early promoter. PMID- 2112089 TI - Structural and functional analysis of ypt2, an essential ras-related gene in the fission yeast Schizosaccharomyces pombe encoding a Sec4 protein homologue. AB - Using the cloned Saccharomyces cerevisiae YPT1 gene as hybridization probe, a gene, designated ypt2, was isolated from the fission yeast Schizosaccharomyces pombe and found to encode a 200 amino acid long protein most closely related to the ypt branch of the ras superfamily. Disruption of the ypt2 gene is lethal. The bacterially produced ypt2 gene product is shown to bind GTP. A region of the ypt2 protein corresponding to but different from the 'effector region' of ras proteins is also different from that of ypt1 proteins of different species but identical to the 'effector loop' of the S.cerevisiae SEC4 gene product, a protein known to be required for vesicular protein transport. The S.pombe ypt2 gene under control of the S.cerevisiae GAL10 promoter is able to suppress the temperature-sensitive phenotype of a S. cerevisiae sec4 mutant, indicating a functional similarity of these GTP-binding proteins from the two very distantly related yeasts. PMID- 2112090 TI - Brittle cornea syndrome: an heritable connective tissue disorder distinct from Ehlers-Danlos syndrome type VI and fragilitas oculi, with spontaneous perforations of the eye, blue sclerae, red hair, and normal collagen lysyl hydroxylation. AB - We report a patient with the characteristic features of the brittle cornea syndrome, a rare, autosomal recessively inherited disorder, namely brittle corneae, blue sclerae, and red hair. The patient also showed joint hyperextensibility, a soft skin, and dysplastic auricles with unusually soft cartilage. Phenotypically, the disorder bears a certain resemblance to fragilitas oculi and the type VI (ocular) form of the Ehlers-Danlos syndrome, two conditions which are, themselves, not readily distinguishable. However, the hydroxylysine content of dermal collagen was normal, as was the activity of lysyl hydroxylase in cultured dermal fibroblasts, thus supporting the distinction of the brittle cornea syndrome as an independent entity. No abnormality was discernible in types I or III collagens synthesised by cultured fibroblasts, but electron microscopy revealed dramatic ultrastructural alterations in dermis in that distributed over its whole thickness were 20-60 microns wide "holes" or fibre-free spaces, filled with an amorphous material. PMID- 2112091 TI - Growth hormone deficiency in children: role of magnetic resonance imaging in assessing aetiopathogenesis and prognosis in idiopathic hypopituitarism. AB - To search for the presence of morphostructural abnormalities of the hypothalamus pituitary region in growth hormone deficient (GHD) children magnetic resonance imaging (MRI) was performed in 30 GHD patients (age 10.09 +/- 3.5 years) and in 15 healthy age-matched controls. MRI demonstrated a significantly small sella and pituitary volume compared to controls and normal literatures values. In 20 patients the structures were extremely small and an abnormal development of the pituitary stalk was observed, and in 18 of these patients the bright spot indicating the neurohypophysis was dislocated to the distal part of the maldeveloped stalk, although these children had a normal fluid balance. From a functional point of view hypothalamus and pituitary defects were equally distributed between the two morphological groups. The patients with multiple endocrine defects had the smallest pituitary volume and abnormal stalk. A possible pathogenetic role of perinatal trauma or dysembryogenic events are discussed. A careful follow up of patients with isolated GHD presenting MRI abnormalities of the pituitary is suggested for the possible evolution in panhypopituitarism. PMID- 2112092 TI - Concurrence of transient asplenia and pure red cell aplasia. AB - We report a 9-year-old male with anatomical asplenia diagnosed at 7 months of age documented by ultrasound and liver-spleen scan which resolved spontaneously 3 years later. The patient concurrently had pure red cell aplasia which subsequently resolved spontaneously. PMID- 2112093 TI - Immunoglobulin-specific T-B cell interaction. III. B cell activation by immunoglobulin-recognizing T cell clones. AB - Immunoglobulin (Ig)-specific T-B cell interactions were studied in the model of T cell recognition of Ig kappa chain Ig kappa-1b allotype in Ig kappa-1-congenic rats. Using Ig kappa-1b-recognizing major histocompatibility complex (MHC) restricted T helper clones from August rats we have shown that Ig kappa-1b+ B cells from congenic August.1b rats presented Ig kappa-1b epitope of the processed self-synthesized Ig to T clones. This interaction was found to be a bidirectional regulatory event inducing specific MHC-dependent proliferation of both interacting T cell and B cell as well as Ig(Ig kappa-1b) synthesis. Small Ig kappa-1b+ B cells were capable of inducing T clone proliferation and becoming activated in response to the same T clone. Limiting dilution analysis suggested that every tenth cell in Ig kappa-1b+ B cell population is involved in this interaction. The bystander activation of Ig kappa-1a+ B cells by T clones in the presence of irradiated Ig kappa-1b+ spleen cells, if observed, was less than the level of specific Ig kappa-1b+ B cell proliferation. In contrast to a 20-fold increase of Ig(Ig kappa-1b) levels upon stimulation of Ig kappa-1b+/1a+ B cell population from heterozygous (August x August.1b)F1 rats by T clones, a "nonspecific" increase of Ig(Ig kappa-1a) was not observed. This result demonstrates the requirement for direct T-B contact for B cell activation to occur. The data suggest a great functional potency of T-B interactions mediated by T cell recognition of Ig-derived peptide/MHC class II complexes on the B cell surface. The implication of the data for idiotypic regulation enables us to propose the existence of putative idiopeptidic network T-B cell interactions. PMID- 2112094 TI - Individual variation in the frequency of HLA class II-specific cytotoxic T lymphocyte precursors. AB - The frequencies of HLA class II-specific cytotoxic T lymphocyte precursors (CTLp) were studied in number of unrelated individuals using a limiting dilution analysis system optimized for the detection of CD4+ CTLp. Peripheral blood mononuclear cells (PBMC) were enriched for CD4+ T cells by immunomagnetic depletion of CD8+ T cells. In some allogeneic combinations high CTLp frequencies were obtained with no significant difference between PBMC and CD4-enriched PBMC populations. In other combinations CTLp frequencies in CD4-enriched PBMC were found to be at least twentyfold lower than in the starting, unfractionated PBMC, suggesting a predominance in these pairs of CD8+ CTLp. In addition there was variation in CTLp frequencies against the same set of HLA class II gene products between individuals, and variation in CTLp frequencies against different HLA class II gene products within individuals. The HLA class II specificity of the assay system was demonstrated unequivocally with detection of CTLp against HLA DR1 expressed on a murine L cell transfectant. PMID- 2112095 TI - T cell receptor gene rearrangements of T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis (PBC): oligoclonality of PBC-derived T cell clones. AB - Immunological events are involved in the pathophysiology of chronic active hepatitis as indicated from the accumulation of T lymphocytes at the site of tissue damage. We generated T cell clones from liver biopsies of 3 patients with chronic active hepatitis B and 2 patients with primary biliary cirrhosis. These T cell clones (n = 84) were analyzed by means of T cell receptor (TcR) beta gene rearrangements to determine whether the infiltrate consists of a polyclonal or oligoclonal T cell population. The vast majority (62 of 64) of T cell clones from three different patients with chronic active hepatitis B showed no identical rearrangements of the TcR beta chain genes. In marked contrast, in both patients with primary biliary cirrhosis, T cell clones established were of limited diversity. Thus 5 out of 10 and 2 out of 10 T cell clones from one patient and 3 out of 9 and 2 out of 9 T cell clones from the second patient, respectively, showed identical TcR beta gene rearrangements. These data suggest that a clonal dominance is characteristic for local T cell responses in autoimmune liver disease such as primary biliary cirrhosis whereas in virus-induced chronic active hepatitis T cell activation occurs polyclonally. PMID- 2112096 TI - Absolute numbers of lymphocytes subsets migrating through the compartments of the normal and transplanted rat spleen. AB - Lymphocyte migration is one of the basic principles of the immune system. Up to now lymphocyte migration experiments have been performed either in a quantitative way, determining whole organ recoveries of radiolabeled lymphocytes without histologic localization, or based on autoradiography which does not provide absolute numbers of immigrant lymphocytes. In this study the traffic of lymphocyte subsets through the splenic compartments: red pulp (RP), marginal zone (MZ), periarteriolar lymphatic sheath (PALS) and follicle was evaluated in absolute numbers. In normal spleens and splenic transplants fluorescein isothiocyanate (FITC)-labeled immigrant lymphocytes were localized and characterized immunohistochemically in cryostat sections by light microscopy. In addition morphometry of the splenic compartments was performed and the recovery of 51Cr-labeled lymphocytes in the spleen was determined. The combination of these methods allowed total numbers of immigrant subset cells to be calculated in individual splenic compartments. At 15 min about 17% of the injected B lymphocytes were found in the MZ. This is the largest fraction of an injected lymphocyte subset found in a single splenic compartment. At 24 h immigrant B cells were not only found in the follicle, but they had reached comparable numbers in the three compartments: follicle, RP and MZ. Most immigrant T lymphocytes were found in the PALS, which from 6 h after injection onwards contained more T cell immigrants than any single organ of the body. CD4+ and CD8+ lymphocytes showed a similar distribution throughout the splenic compartments at early time points. At 24 h CD4+ lymphocytes homed preferentially to the PALS, whereas CD8+ cells seemed to prefer the RP and MZ. Both CD4+ and CD8+ cells also migrated into the follicles. In regenerated splenic tissue after autotransplantation lymphocyte immigration was reduced in all compartments and to the MZ in particular. An impaired lymphocyte migration to the MZ in splenic transplants may be one reason for the lack of protection provided against bacterial infections. Thus examining lymphocyte migration in absolute numbers provides additional information which cannot be gained by determining labeling indices or percentages of lymphocyte subsets alone. PMID- 2112097 TI - Identification of hemolytic granules isolated from human myocardial cells. AB - Human myocardial cells from fresh autopsy material contained granules which possessed hemolytic activity against guinea pig and rabbit erythrocytes. The hemolytic granules, which had a density of 1.02 and a diameter of 200-300 nm, were recovered as a microsome fraction from subcellular homogenates of human myocardial cells by differential centrifugation in 300 mM sucrose containing 0.1 mM PMSF and 10 mM EDTA. The membrane lesions caused by the granules were ring like structures with an internal diameter of about 10-17 nm, analogous to that caused by perforin- and complement-induced lysis. However, the requirement for divalent cation differed from that for perforin-induced lysis, since the microsome-mediated lysis occurred in the presence of EDTA. PMID- 2112098 TI - Serious chemical sclerosing cholangitis associated with hepatic arterial 5FU and MMC chemotherapy. AB - A case of iatrogenic sclerosing cholangitis secondary to hepatic intra-arterial 5 fluorouracil (5FU) and Mitomycin C (MMC) chemotherapy is described. When any unexplained elevation of liver function results in alkaline phosphatase and bilirubin level, chemotherapy should be discontinued, and further examination carried out using ultrasonography, transhepatic cholangiography and endoscopic retrograde cholangio-pancreatography (ERCP). Although percutaneous transhepatic biliary drainage has been effective in some cases, in our case, the clinical course was irreversible and the patient died of hepatic failure and gastrointestinal bleeding. When clinical signs of hepatic dysfunction occur in the absence of tumor progression, iatrogenic sclerosing cholangitis must be suspected. PMID- 2112099 TI - Tetravalent vanadium mediated oxidation of low density lipoprotein. AB - 1. Tetravalent vanadium causes oxidation of low density lipoprotein (LDL) as manifest by protein degradation and lipid peroxidation. 2. Oxidative modification of the apolipoprotein B-100 is paralleled by the formation of thiobarbituric acid reactive substance and fluorescent chromolipid production. 3. The metal chelators ethylenediamine tetracetic acid and desferrioxamine, and the alcohols, ethanol and isopropanol inhibit the oxidation of LDL by tetravalent vanadium. No inhibition is observed with superoxide dismutase, catalase or mannitol. 4. The data suggest that aldehydes formed during the process of lipid peroxidation induced by tetravalent vanadium react with the proteins in LDL to form fluorescent chromolipids and that the oxidative process originates within the hydrophobic domain of LDL. PMID- 2112100 TI - The clinical and hormonal (C-peptide and glucagon) profile and liability to ketoacidosis during nutritional rehabilitation in Ethiopian patients with malnutrition-related diabetes mellitus. AB - Cases of malnutrition-related diabetes mellitus conforming to the description of the protein deficient pancreatic diabetes type in Ethiopian patients were compared with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic. Fourteen of 39 malnutrition-related diabetes mellitus patients had fat malabsorption compared with only two of ten Type 1 diabetic patients and one of nine control subjects. Xylose absorption was normal favouring a pancreatic cause for the malabsorption. Plasma C-peptide during oral glucose tolerance test was significantly lower than that in Type 2 diabetic patients and normal control subjects (p less than 0.01 to 0.001) and was also consistently but not significantly higher than in Type 1 diabetic patients. Glucagon secretion patterns were similar in malnutrition-related and Type 1 diabetic patients. Of 23 new malnutrition-related diabetic patients treated with glibenclamide after nutritional rehabilitation and insulin treatment, only three responded, 14 were unresponsive but remained ketosis free for over eight days while another six developed ketoacidosis or significant ketonuria within two to six days during the trial. Sixteen unselected Type 1 diabetic patients who discontinued their insulin therapy all developed frank ketoacidosis after a mean of 5.5 days. The similarity of the malnutrition-related and Type 1 diabetes mellitus in age of onset, insulin requirement for diabetic control and appearance of ketosis-proneness in some cases, together with the similarity of C-peptide and glucagon secretion patterns suggest that the protein deficient pancreatic diabetes variant of malnutrition related diabetes mellitus may be Type 1 diabetes mellitus modified by the background of malnutrition rather than an aetiologically separate entity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112101 TI - [A clinical case. Infectious endocarditis]. PMID- 2112102 TI - Antibodies to hepatitis C virus in non-A non-B fulminant viral hepatitis. PMID- 2112103 TI - Steroidal modulation of pituitary gonadotropin-releasing hormone responsiveness in young turtles, Pseudemys scripta. AB - Steroid-modulated pituitary secretion and glandular content of gonadotropin (Gth: LH and FSH) was studied in young slider turtles. Injection (ip) of both 17 beta estradiol (E2) and testosterone (T) reduced pituitary content of both Gths and caused significant inhibition of basal LH secretion and gonadotropin-releasing hormone (GnRH)-stimulated LH and FSH secretion measured in vitro. However, gonadectomy did not affect pituitary Gth secretion or response in these juveniles, and anti-estrogen and anti-androgen compounds had some steroid agonistic action on the pituitary gland. Exposure to E2, T, and 5 alpha dihydrotestosterone (DHT) in vitro for 4, 24, or 48 hr either had no effect or completely inhibited pituitary GnRH responsiveness. Progesterone (P) alone had no effect on pituitary GnRH response and in combination did not alter the typical inhibitory effect of E2. There were several indications of differential effects of steroids on secretion of the two Gths, especially in response to GnRH and tetraethyl chloride (receptor independent) stimulation. The results suggest that steroids may act directly at the pituitary level to alter Gth secretion and that steroidal modulation of pituitary secretion might play a role in differential regulation of LH and FSH in turtles. PMID- 2112104 TI - Trout steroidogenic testicular cells in primary culture. II. Steroidogenic activity of interstitial cells, Sertoli cells, and spermatozoa. AB - Somatic cells (interstitial cells and Sertoli cells) were prepared either as single cells or in clusters, from spermatogenic and mature trout testes, according to Loir (1988), and cultured for 10-14 days. Sertoli cells are 3 beta HSD negative when prepared from testes resuming spermatogenesis and from mature testes, but they are 3 beta-HSD positive in spermatogenic testes. Progesterone, 17 alpha-hydroxyprogesterone (17 alpha-OH-P), and free androgens are secreted by interstitial cells, 11-ketotestosterone (11KT) being the predominating steroid produced immediately after seeding. These cells also produce high levels of glucuronated androgens. At least in mature spermiating testes they do not secrete estradiol. After isolation, interstitial cells would lose most of their ability to secrete 17 alpha-hydroxy,20 beta-dihydroprogesterone (17 alpha 20 beta-OH-P) but they would recover it later. Testicular spermatozoa, which convert 17 alpha OH-P independently of s-GtH, constitute a second source of this progestagen. In addition, our results suggest that Sertoli cells could be able to secrete 17 alpha-OH-P and also progesterone. A possible participation of the intralobular production of the former progestagen to the local regulation of germ cell maturation is evoked. PMID- 2112105 TI - Regulation of human glutathione S-transferase pi gene transcription: influence of 5'-flanking sequences and trans-activating factors which recognize AP-1-binding sites. AB - To investigate the transcriptional regulation of human glutathione S-transferase pi (GST pi) gene expression, we fused the GST pi promoter, including 2203 bp of the 5'-flanking region, exon 1, and most of intron 1, to the chloramphenicol acetyltransferase (CAT)-encoding reporter gene (cat). When transfected into human cell lines, this GST-cat construct (-2203 GST-cat) supported high level cat gene expression. RNase-protection and primer-extension experiments showed that the normal GST pi transcriptional start point (tsp) is utilized, and furthermore, that intron 1 is faithfully removed by splicing from the majority of primary GST cat transcripts. A series of constructs containing deletions in the GST pi sequences of the -2203 GST-cat vector were prepared to define potential regulatory regions. Transfection of these deletion plasmids revealed that a region between GST pi sequences -80 and -8 is absolutely required for cat expression. Furthermore, transfection of the -2203 GST-cat and deletion vectors into two human cell lines--one line which does not produce endogenous GST pi (HeLa cells) and one which produces high levels of endogenous GST pi (HS 578T cells)--failed to identify sequences that differentially influence the level of transcription in either cell line. A putative TRE (TPA responsive element or AP-1 recognition sequence) strategically situated upstream from the GST pi tsp (-69 to -63) was examined by TPA treatment of HeLa cells transfected with GST-cat DNA. Additionally, the potential interaction of fos and jun proteins with the GST pi promoter was examined by co-transfection of GST-cat constructs with jun and fos expression vectors in F9 cells. Both of these treatments, which are known to enhance transcription of several genes containing 5'-flanking TREs, failed to induce GST-cat expression. These data suggest that the putative TRE sequence in GST pi is unresponsive both to phorbol esters and to these particular transcriptional activating factors of the fos and jun family. PMID- 2112106 TI - The promoter of the glucoamylase-encoding gene of Aspergillus niger functions in Ustilago maydis. AB - Promoter sequences from the Aspergillus niger glucoamylase-encoding gene (glaA) were linked to the bacterial hygromycin (Hy) phosphotransferase-encoding gene (hph) and this chimeric marker was used to select Hy-resistant (HyR) Ustilago maydis transformants. This is an example of an Ascomycete promoter functioning in a Basidiomycete. HyR transformants varied with respect to copy number of integrated vector, mitotic stability, and tolerance to Hy. Only 216 bp of glaA promoter sequence is required for expression in U. maydis but this promoter is not induced by starch as it is in Aspergillus spp. The transcriptional start points are the same in U. maydis and A. niger. PMID- 2112107 TI - Lessons from the implementation of CCRC regulation. AB - Oversight staff in 23 of the 30 states with legislation regulating continuing care retirement communities (CCRCs) completed a questionnaire surveying features of implementation experience such as problems encountered with the scope of regulation, the appropriateness of oversight placement, the adequacy of staff and financial resources, the use of discretionary agency authority, and attitudes toward various changes in applicable state law. These findings have relevance for consumers, legislators, lobbyists, and professionals working to make CCRCs a responsible long-term care alternative. PMID- 2112108 TI - The no-care zone: availability, accessibility, and acceptability in community based long-term care. AB - Community-based care for chronic illness requires a continuum of services. This article identifies three aspects of the organization of long-term care that are important in maintaining a continuum: availability, accessibility, and acceptability. Each category is illustrated by data from Missouri to demonstrate potential problems in each of the three areas that can prevent the chronically ill from obtaining needed services. PMID- 2112109 TI - Levonorgestrel and norethindrone alter insulin action on skeletal muscle of the female rat. AB - Prospective studies of women receiving oral contraceptives suggest that the progestin component may induce insulin resistance and variable deterioration of glucose tolerance. Because the tissue sites and nature of this insulin antagonism are not well-defined, we studied the effects of two parenterally administered progestins, levonorgestrel (NG) and norethindrone (NE), on insulin-regulated glucose uptake and phenylalanine release by the perfused rat hindquarter. Female rats were injected sc for 14 days with NG or NE (10 or 30 micrograms/kg/day). Low dose NG and high-dose NE approximate the per kg dose received by women taking a high-dose progestin oral contraceptive. Phenylalanine release and glucose uptake (nmole/min/g) by the perfused hindquarters were calculated from the A-V difference for each. Progestin treatment (30 micrograms/kg/d) significantly reduced phenylalanine release from hindquarters perfused without exogenous insulin. Hindquarters from the high dose NG and low and high dose NE rats perfused with insulin (100 microU/ml) released 22% less phenylalanine than control rats perfused with the same insulin concentration (P less than 0.01) but the net suppression below baseline was similar in the control and steroid-treated groups. High-dose progestin treatment did not alter glucose uptake by hindquarters perfused without exogenous insulin. Insulin (100 microU/ml) increased glucose uptake by hindquarters of control and progestin-treated rats as compared to animals in the same treatment group perfused without exogenous insulin (P less than 0.01). High dose NE impaired insulin-stimulated glucose uptake 24% below values of the control group (P less than 0.01). The other NE and NG doses had no effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112110 TI - Comparisons of insulin and biosynthetic human proinsulin actions in cultured hepatocytes. Kinetics and biologic potencies. AB - The binding and biologic potencies as well as kinetics of action of human biosynthetic proinsulin (HPro) were studied in primary cultures of rat hepatocytes. HPro had 3% (on a molar basis) of the potency of porcine insulin for displacing (125I)-TyrA14-insulin from receptors. Maximally effective concentrations of insulin and HPro caused similar stimulations of 14C-glucose incorporation into glycogen and glycogen synthase activity. However, the dose response curve for HPro stimulation of glycogen synthase was shifted far to the right (EC50 = 4.1 +/- 1.1 nM) of that for insulin (.09 +/- .01). The relative biologic potency of HPro was approximately 3%. Biologically equivalent maximal doses of insulin (8.3 nM) and HPro (53.2 nM) stimulated glycogen synthase activity with similar time courses; half maximal between 15-30 min with maximal effects at 60 min. Deactivation of glycogen synthase upon removal of the hormone was very rapid for both hormones. The relative binding and biologic potencies of HPro compared to insulin in liver (approximately 3%) were similar to values previously seen in adipocytes. This fact, together with the similarity of kinetics of action, suggest that the in vivo hepatoselectivity of HPro is not a property of the target cell itself. PMID- 2112111 TI - Screening of geriatric patients for thyroid dysfunction with thyrotropin releasing-hormone test, sensitive thyrotropin and free thyroxine estimation. AB - Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH. PMID- 2112112 TI - Presence of functional cytochrome P-450 on isolated rat hepatocyte plasma membrane. AB - Antibodies against cytochrome P-450 are found in some children with autoimmune hepatitis (antiliver/kidney microsome 1) and in patients with ticrynafen hepatitis (antiliver/kidney microsome 2). For an immune reaction against cytochrome P-450 to possibly destroy the hepatocytes, one must assume that cytochrome P-450 is present on the plasma membrane surface of hepatocytes. In a first series of experiments, plasma membranes were prepared with a technique based on the electrostatic attachment of isolated hepatocytes to polyethyleneimine-coated beads. After vortexing, beads were coated with a very pure plasma membrane fraction. Microsomal contamination, judged from the specific activities of glucose-6-phosphatase or NADH-cytochrome c reductase, was less than 1%. Nevertheless, the specific content (per milligram of protein) of CO-binding cytochrome P-450 was 20% of that in microsomes; the specific benzo(a)pyrene hydroxylase activity was 25%, and ethoxycoumarin deethylase 11%. Immunoblots showed the presence of cytochromes P-450 UT-A, UT-H, PB-B, ISF-G and PCN-E, the last three isoenzymes being inducible by, respectively, phenobarbital, 3 methylcholanthrene and dexamethasone. In a second series of experiments, nonpermeabilized isolated hepatocytes from untreated rats were incubated with anticytochrome P-450 antibodies. Immunofluorescence and immunoperoxidase staining confirmed the presence of cytochromes P-450 UT-A, PB-B and ISF-G on the membrane. In a last series of experiments, human antiliver-kidney microsomal 1 antibodies were found to react specifically with rat liver plasma membrane cytochrome P-450 UT-H (IID subfamily). We conclude that several cytochrome P-450 isoenzymes are present, active and inducible on the plasma membrane surface of hepatocytes. It is therefore conceivable that immunization against plasma membrane cytochrome P 450 might lead to the immunological destruction of hepatocytes in some patients. PMID- 2112113 TI - Nuclear localization of antigens detected by a monoclonal antibody against a synthetic peptide of rfp finger protein. AB - A monoclonal antibody (MAb) was generated against a synthetic peptide corresponding to amino acids 148 to 163 of the rfp protein with zinc finger domains. The MAb, designated RFP-1 (IgM), which was positive with the immunizing peptide in enzyme-linked immunosorbent assay, was reactive in immunoblotting with an in vitro translated rfp product as well as with native proteins in cell extracts made from mouse testis and HL-60 human leukemia cell line, both of which were previously shown to express high levels of rfp mRNA. When HL-60 cells were fractionated into nuclear and cytoplasmic components, the protein reactive with RFP-1 MAb was detectable only in the nuclear fraction. By the avidin-biotin complex immunoperoxidase method, this MAb strongly stained over 90% of the nuclei of human and mouse spermatogenic cells, except mature spermatozoon, and of human testicular tumor cells. In other human adult tissues, up to 60% of positive cells were observed. These antibody activities were clearly absorbed by pre-incubation of RFP-1 MAb with the immunizing peptide. These results thus indicated that RFP-1 MAb recognizes a nuclear protein which is expressed at high levels in male germ cells. PMID- 2112114 TI - Interleukin-1 and tumor necrosis factor synthesis by mouse peritoneal macrophages is enhanced by dietary n-3 polyunsaturated fatty acids. AB - The peritoneal macrophages from mice maintained for 16 days on a diet containing (10%) menhaden oil contained less arachidonic acid and more n-3 polyunsaturated fatty acids (n-3 PUFA) than those maintained on diets containing an equivalent amount of corn oil. Following stimulation with lipopolysaccharide, the production of PGE2, interleukin-1 (IL-1) and tumor necrosis factor (TNF) was 2.1 vs. 5.3 ng PGE2/micrograms DNA; 685 vs. 30 units IL-1/micrograms DNA and 14 vs. less than 4 units TNF by macrophages from mice consuming menhaden and corn oil, respectively. Macrophages from animals on diets containing olive oil generated intermediate amounts of PGE2 and equivalent amounts of IL-1 and TNF to those on corn oil. The data indicate that dietary n-3 PUFA at specific intake levels relative to n-6 PUFA may enhance cytokine generation by reducing PGE2 synthesis. PMID- 2112115 TI - Intestinal glucoamylase & other disaccharidases in children with protracted diarrhoea. AB - Brush border lactase, sucrase and glucoamylase activities were assessed in jejunal mucosal biopsy specimens from 34 children (median age 11 months; range 1.5-38) having protracted diarrhoea with failure to thrive and 8 well nourished children with normal jejunal mucosal histology (median age 10.2 months; range 2 37). All enzymes showed progressive decrease in activity which was directly in relation to increasing degree of mucosal injury (P less than 0.002). Lactase was significantly reduced even in patients with protracted diarrhoea and normal mucosa (P less than 0.05). Glucoamylase and sucrase were significantly reduced only in the presence of mucosal injury (P less than 0.01). Our data suggest that most children with protracted diarrhoea may not tolerate lactose containing feeds and may need lactose-free diets preferably based on starch. A small number of children with protracted diarrhoea, who have severe mucosal injury may not be able to handle even starch and may require diets based on short chain glucose polymers. The findings of this study, need to be corroborated with well controlled metabolic balance studies. PMID- 2112116 TI - Spectrophotometric analysis of amniotic fluid in Rh immunised pregnancies. AB - A total of 307 amniotic fluid analysis done in 344 Rh negative immunised mothers showed that 46, 83 and 178 delta OD values at 450 millimicrons fell in the upper, middle and lower zones of Liley's charts respectively. The correlation of spectrophotometric analysis with the condition of the baby at birth was about 95 per cent in the upper and lower zones. In the middle zone, however, it was about 75 per cent only. Also, in 7 women in whom the OD at 450 millimicrons fell in the middle zone, the babies were found to be Rh negative; in another baby, the OD difference fell in upper zone. In spite of these limitations amniotic fluid examination seems to be an important single guide to severity, being superior to other parameters like previous obstetric history, antibody titre alone and Liley's charts, which are still widely used. PMID- 2112117 TI - Quantitation of Ina blood group antigens. AB - Using indirect immunoradiometric assay the mean (+/- SD) number of Ina antigenic sites per erythrocyte was estimated to be 73857 +/- 18285 in normal adults and 20142 +/- 8571 in newborn infants. Pregnant women showed temporary reduction in Ina antigens (28144 +/- 13857), which returned to normal levels, 3-6 months after delivery. Ina antigens were shown to be denatured by papain treatment of red cells, proving it to be of glycoprotein nature. PMID- 2112118 TI - Exposure to formaldehyde and glutardialdehyde in operating theatres. AB - The disinfection of operating theatres and adjoining areas is carried out with chemical disinfectants containing not only formaldehyde but also glutardialdehyde. The cleaning staff is therefore unavoidably exposed to these two substances. Adequate and correct evaluation of staff exposure must be based on exact quantification of these aldehydes in room air. The statutory MAK-levels of 0.5 ppm (formaldehyde) and 0.2 ppm (glutardialdehyde) call for highly sensitive and specific analytical methods for monitoring exposure that should be suited for personal measuring as well. Since previous methods have failed to meet these requirements, we have adapted a newly developed method for the specific measurement of formaldehyde and other aldehydes and ketones for the personal monitoring of formaldehyde and glutardialdehyde. Detailed personal measurings over whole shifts and of short-term peaks have yielded the following results: During routine disinfection activities in operating theatres using low concentrations of disinfectants, the limits prescribed by MAK can be respected. Disinfections to prevent notifiable infectious diseases in accordance with the Federal Epidemic Law (Bundesseuchengesetz) involving the use of higher disinfectant concentrations are liable to exceed the MAK limits for formaldehyde and glutardialdehyde. If for reasons of hygiene this excess exposure cannot be avoided, effective protection of the cleaning staff from unacceptably high concentrations of these substances can be ensured only by providing personal protective outfits. PMID- 2112119 TI - Hemodialysis-related induction of beta 2-microglobulin synthesis and release by mononuclear phagocytes. AB - We have investigated beta 2-microglobulin (beta 2M) synthesis and release by blood leukocytes and isolated mononuclear phagocytes. Since beta 2M was discovered to form amyloid fibrils in patients undergoing long term, chronic hemodialysis and monomeric beta 2M levels in plasma of these patients are highly elevated, and since hemodialysis-related factors that increase beta 2M production are unknown, we evaluated beta 2M production by mononuclear phagocytes under a variety of conditions. We utilized a novel enzyme-lined immunoabsorbant assay to quantitate beta 2M release. Adherence of macrophages onto polystyrene or Cuprophan membranes does not induce beta 2M synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin 1 induces synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin 1 induces synthesis and release of beta 2M, indicating that beta 2M synthesis is increased during macrophage activation. Exposing leukocytes or macrophages to changes in osmotic or oncotic pressure induces a rapid release of beta 2M and interleukin 1 into the cellular medium. These results suggest that during hemodialysis, beta 2M production is more likely to result from endotoxin contamination, or osmotic and oncotic changes, rather than direct interaction of mononuclear phagocytes with cellulosic membranes. PMID- 2112120 TI - Randomized trial comparing single dose versus fractionated irradiation for prevention of heterotopic bone: a preliminary report. AB - Radiation therapy has been shown to prevent heterotopic bone formation in high risk patients undergoing total hip replacement. A number of doses have been used without a randomized trial comparing one dose regimen against another. A prospective randomized trial was undertaken comparing 10 Gy in 5 fractions versus 8 Gy in 1 fraction. Forty-seven patients have been randomized at the time of this evaluation with 37 patients eligible for analysis. The pre-operative, immediate post-operative and 2 month post-operative radiographs were graded. At the time of this analysis, 17 patients were randomized to the 8 Gy arm with 20 patients in the 10 Gy arm. Patients were treated with limited fields so as to only cover the area at risk for development of heterotopic bone to prevent adverse effects on biologic fixation of uncemented implants. When comparing the pre-operative, operative, and 2 month post-operative radiographs, only four patients (1 patient in the 8 Gy arm and 3 patients in the 10 Gy arm), had an increase in the score. No patient had an increase in score to a clinically significant level, usually grade 3 or 4. These preliminary results appear to show that 8 Gy in a single fraction can be as effective as 10 Gy in 5 fractions in preventing heterotopic bone in susceptible individuals. Further follow-up of the remaining patients may confirm this. PMID- 2112121 TI - Shielding considerations for an operating room based intraoperative electron radiotherapy unit. AB - The leakage radiation characteristics of a dedicated intraoperative radiotherapy linear accelerator have been measured on a machine designed to minimize the shielding required to allow it to be placed in an operating room suite. The scattering foil design was optimized to produce a flat beam for the field sizes employed while generating minimal bremsstrahlung contamination over the available energy range. More lead shielding was used in the treatment head than is used in conventional accelerators. A small amount of borated polyethylene shielding was also employed since neutron production was present at measurable levels. The room shielding installed in the operating room was demonstrated to be adequate to treat at least 20 patients each month to an average dose of 20 Gy. The worst case exposure was found to be 73% maximum permissible exposure. Administrative control was required for adjoining areas when calibrations and maintenance were performed. PMID- 2112122 TI - Electrolyte abnormalities associated with diarrhea in rhesus monkeys: 100 cases (1986-1987). AB - Serum electrolyte values from 100 rhesus monkeys with diarrhea were reviewed. The most frequent finding was hyponatremia (88%), with hypochloremia next most frequently detected (80%). Metabolic acidosis was less common (59%) and usually associated with high anion gap values. Associations between electrolyte abnormalities and age, housing, or case outcome were not found. Bacteriologic culturing was performed on fecal specimens from 90 monkeys. Campylobacter coli or C jejuni alone was isolated from 42 (46.7%) specimens, C coli and Shigella flexneri were isolated from 25 (27.8%) specimens, and S flexneri alone was isolated from 6 (6.7%) specimens. A pathogen was not isolated from 17 (18.9%) specimens. Hyponatremia, hypochloremia, acidosis, and high anion gap values were most severe in monkeys infected with Campylobacter sp, either alone or with concurrent S flexneri infection. Serum sodium concentrations less than 132 mEq/L and serum Cl concentrations less than 93 mEq/L were consistently associated with Campylobacter sp infection. PMID- 2112123 TI - Methods for inactivating experimentally induced scrapie in hamster tissues. PMID- 2112124 TI - The antibiotic sensitivity of bacteria isolated from the blood of patients in St Thomas' Hospital, 1969-1988. AB - We have monitored the antibiotic sensitivity of bloodstream isolates of common bacteria over a period of 20 years. Among the Gram-positive bacteria, the proportion of isolates of Staphylococcus aureus resistant to methicillin, erythromycin, fusidate, or gentamicin has increased marginally, while that of coagulase-negative staphylococci (mostly Staph. epidermidis) has increased markedly. Enterococci are becoming serially more resistant to high concentrations of aminoglycosides. The Enterobacteriaceae have become considerably less sensitive to ampicillin (and amoxycillin) and trimethoprim but more sensitive to the aminoglycosides, whilst their susceptibility to cefotaxime, ceftazidime, cefepime, cefpirome, imipenem, meropenem and temocillin has remained constant. We have some evidence that in-vitro resistance is clinically relevant since the mortality rate rises if inappropriate antibiotics are used empirically. Although many drug regimens could be used, we are able to recommend initial therapy with a combination of gentamicin and cefuroxime for most of our patients, the exceptions being those known to be infected with resistant organisms before the onset of septicaemia. PMID- 2112125 TI - Increases in coronary vein CO2 during cardiac resuscitation. AB - We investigated the aortic, mixed venous, and great cardiac vein acid-base changes in eight domestic pigs during cardiac arrest produced by ventricular fibrillation and during cardiopulmonary resuscitation (CPR). The great cardiac vein PCO2 increased from a control value of 52 +/- 2 to 132 +/- 28 (SD) Torr during CPR, whereas the arterial PCO2 was unchanged (39 +/- 4 vs. 38 +/- 4). The coronary venoarterial PCO2 gradient, therefore, increased remarkably from 13 +/- 2 to 94 +/- 29 Torr. The simultaneously measured great cardiac vein lactate concentrations increased from 0.24 +/- 0.06 to 7.3 +/- 2.34 mmol/l. Much more moderate increases in the lactate content of aortic blood from 0.64 +/- 0.25 to 2.56 +/- 0.27 mmol/l were observed. Increases in great cardiac vein PCO2 and lactate were highly correlated during CPR (r = 0.91). After successful CPR, the coronary venoarterial PCO2 gradient returned to normal levels within 2 min after restoration of spontaneous circulation. Lactate content was rapidly reduced and lactate extraction was reestablished within 30 min after CPR. These studies demonstrate marked but reversible acidosis predominantly as the result of myocardial CO2 production during CPR. PMID- 2112126 TI - Adjustments in oxygen transport during head-out immersion in water at different temperatures. AB - Respiratory gas exchange was investigated in human subjects immersed up to the shoulders in water at different temperatures (Tw = 25, 34, and 40 degrees C). Cardiac output (Qc) and pulmonary tissue volume (Vti) were measured by a rebreathing technique with the inert gas Freon 22, and O2 consumption (VO2) was determined by the closed-circuit technique. Arterial blood gases (PaO2, PaCO2) were analyzed by a micromethod, and alveolar gas (PAO2) was analyzed during quiet breathing with a mass spectrometer. The findings were as follows. 1) Immersion in a cold bath had no significant effect on Qc compared with the value measured at Tw = 34 degrees C, whereas immersion in a hot bath led to a considerable increase in Qc. Vti was not affected by immersion at any of the temperatures tested. 2) A large rise in metabolic rate VO2 was only observed at Tw = 25 degrees C (P less than 0.001). 3) Arterial blood gases were not significantly affected by immersion, whatever the water temperature. 4) O2 transport during immersion is affected by two main factors: hydrostatic pressure and temperature. Above neutral temperature, O2 transport is improved because of the marked increase in Qc resulting from the combined actions of hydrostatic counter pressure and body heating. Below neutral temperature, O2 transport is altered; an increase in O2 extraction of the tissue is even calculated. PMID- 2112127 TI - Effect of hyperoxemia and ritanserin on skeletal muscle microflow. AB - Serotonin2 (5-HT2) receptor antagonists (ketanserin, ritanserin) can normalize a hyperoxemia-induced disturbance in skeletal muscle oxygenation, presumably by local microflow changes. The purpose of this study was to develop equipment for local hydrogen clearance measurements with a modified eight-channel platinum electrode to assess changes in local skeletal muscle capillary blood flow induced by hyperoxemia and ritanserin (0.035 mg/kg) during hyperoxemia. Laser-Doppler flowmetry was used for regional microflow measurements. Two groups of six anesthetized and artificially ventilated rabbits were studied: group I with normoxemia and hyperoxemia [arterial PO2 (PaO2) 48 kPa; 360 Torr] and group II before and after ritanserin with hyperoxemia (PaO2 46 kPa; 345 Torr). In group I, hyperoxemia induced a mean local hydrogen clearance decrease of 22% while laser Doppler flowmetry signal decreased 31%. In group II, ritanserin induced a 125% mean local hydrogen clearance increase compared with hyperoxemia (or 37% compared with group I normoxemia); laser-Doppler flowmetry signal increased 30%. The sum distribution of local hydrogen clearances shifted to the left during hyperoxemia and to the right after ritanserin. The conclusion from this study is that local and regional microflow changes can explain the effects of hyperoxemia and ritanserin on skeletal muscle oxygenation. PMID- 2112129 TI - Role of leukotriene C4 in pulmonary hypertension: platelet-activating factor vs. hypoxia. AB - The aim of this study was to determine whether leukotriene C4 (LTC4) is a mediator of hypoxic pulmonary vasoconstriction. We hypothesized that similar increases in LTC4, detected in the lung parenchyma and pulmonary vascular compartment during cyclooxygenase blockade with indomethacin (INDO), would be observed during an equal increase in pulmonary arterial pressure caused by acute alveolar hypoxia (HYP, 100% N2) or platelet-activating factor (PAF, 10 micrograms into the pulmonary artery). Rat lungs were perfused at constant flow in vitro with an albumin-Krebs-Henseleit solution. Mean pulmonary arterial pressure (n = 6 per group) increased from a base line of 10.9 +/- 1.2 to 15.8 +/- 2.1 (HYP + INDO) and 15.5 +/- 1.9 (SE) Torr (PAF + INDO). LTC4 levels increased only in response to PAF + INDO; perfusate levels increased from 0.4 +/- 0.07 to 5.3 +/- 1.1 ng/40 ml, and lung parenchymal levels increased from 1.9 +/- 0.07 to 22.8 +/- 5.3 ng/lung. Diethylcarbamazine (lipoxygenase inhibitor) reduced PAF-induced lung parenchymal levels of LTC4 by 68% and pulmonary hypertension by 63%. We conclude that 1) LTC4 is not a mediator of hypoxic pulmonary vasoconstriction and 2) intravascular PAF is a potent stimulus for LTC4 production in the lung parenchyma. PMID- 2112128 TI - Effects of changes in osmolarity on isolated human airways. AB - The effects of hypo- and hyperosmolarity on the function of isolated human airways were studied. Changes in osmolarity induced an increasing bronchoconstriction that was proportional to the magnitude of the change in osmolarity. Hypertonicity-induced airway narrowing resulted when buffer was made hypertonic with sodium chloride or mannitol but not with urea. The airways showed no tachyphylaxis to repetitive exposure to hypo- and hypertonic buffer of 200 and 600 mosM, respectively. The bronchoconstriction was not secondary to stimulation of H1 or leukotriene C4/D4 receptors or the release of prostaglandins in the preparation. The bronchoconstriction in hypotonic buffer was totally dependent on extracellular calcium, whereas in hypertonic buffer the bronchoconstriction seemed partially dependent on intracellular calcium release. Isoprenaline prevented the bronchoconstriction in hyper- or hypotonic buffer of 450 and 250 mosM but not in buffer of 600 and 150 mosM. It is concluded that hypo- and hypertonic buffers lead to bronchoconstriction via different mechanisms, which relate to influx of extracellular calcium in hyposmolar buffer and probably to release of calcium from intracellular stores in hypertonic buffer. In strongly hypertonic buffer, part of the bronchoconstriction may be due to osmotic shrinkage. The relevance of our data for the mechanism of bronchoconstriction after inhalation of hypo- or hypertonic saline depends on whether changes in osmolarity around the airway smooth muscle occur in asthmatics but not in normal subjects, and this has not yet been established. PMID- 2112130 TI - A comparison of indirect methods for continuous estimation of arterial PCO2 in men. AB - Four different measures (PETCO2, PACO2, PADCO2, and PJCO2) for indirectly estimating arterial PCO2 (PaCO2) from respired gas at the mouth have been investigated. PETCO2 was the end-tidal PCO2. PACO2 was calculated using a reconstruction of the alveolar oscillation of PCO2 obtained from the end-tidal "plateau" in PCO2. PADCO2 was calculated as for PACO2 except that the effects of dead space were incorporated. PJCO2 was calculated from an empirical relationship involving PETCO2 and tidal volume. Six subjects were studied at rest and during cycle ergometry at 50 and 100 W while breathing a variety of gas mixtures. Arterial samples were drawn for determination of true PaCO2. The differences for each method between estimated and true PaCO2 at rest and at 50 and 100 W were as follows: PETCO2, -1.35 +/- 2.64, 1.67 +/- 2.31, and 2.67 +/- 2.02 (SD) Torr; PaCO2, -2.15 +/- 2.73, -0.80 +/- 2.18, and -0.35 +/- 2.31 (SD) Torr; PADCO2, 1.55 +/- 2.54, 0.25 +/- 2.16, and 0.63 +/- 2.26 (SD) Torr; and PJCO2, -1.41 +/- 2.30, 0.12 +/- 1.79, and 0.08 +/- 1.96 (SD) Torr. It is concluded that, at rest, all methods significantly underestimate true PaCO2 and during exercise PETCO2 significantly overestimates PaCO2, but no bias was detected for any of the other methods. PMID- 2112131 TI - Effect of 4% lidocaine inhalation in bronchial asthma. AB - The effect of 4% lidocaine inhalation was studied in a single-blind fashion in 18 patients with chronic stable asthma. Inhalation of normal saline solution was used as placebo. None of the parameters except flow rate at 50% of vital capacity (V50) showed any statistically significant change from baseline values. V50 at 15 min was significantly lower (p less than 0.05) after 4% lidocaine inhalation. Considering more than 10% change from the baseline value as significant, 8 of 15 patients showed decrease in airway resistance (Raw) and 7 of the 15 patients showed an increase in specific airway conductance (SGaw) after 15 min of inhalation. However, V50 (8/18 patients), flow rate at 25% vital capacity [V25 (6/15 patients], and forced expiratory flow rate at 25-75% of the vital capacity (FEF25-75) (5/15 patients) showed a decrease after 15 min of 4% lidocaine inhalation. No change in pulmonary function was noted after 30 min of lidocaine inhalation. It is concluded from this study that lidocaine produces a small bronchodilatory effect on the large airways and a bronchoconstrictor effect on the small airways after 15 min of inhalation, but this effect is not statistically significant. It can be safely used as topical agent for bronchoscopy in patients with bronchial asthma. PMID- 2112132 TI - Treatment-resistant depression: definition and treatment approaches. AB - Little systematic attention has been directed toward the subject of treatment resistant depression. Although these patients constitute a distinct minority, their treatment consumes a major portion of the clinician's time. Thus, the authors address the problems of defining and treating the estimated 750,000 patients with treatment-resistant depression. Several major factors concerning treatment-resistant depression appear evident: (1) although there is an emerging consensus of what constitutes "adequate" treatment, the majority of patients receive suboptimal drug regimens; (2) misdiagnosis of depression subtypes can lead to suboptimal treatment and "pseudo-resistance" to drug therapy; (3) treatment strategies for resistant depression should use systematic algorithms to avoid confusion and limit "therapeutic nihilism" in the patient and physician; and (4) the patient's risk/benefit ratio for each successive treatment application must be considered with the potential benefit weighed against the increasing risk of illness morbidity and likelihood of adverse events and/or suicide. PMID- 2112133 TI - Structure of O-glycosidically linked oligosaccharides synthesized by the insect cell line Sf9. AB - The O-glycosidically linked oligosaccharides on the pseudorabies virus (PRV) glycoprotein gp50 synthesized by three different cell lines were studied. The intact membrane protein (gp50) was expressed in Vero cells and in the insect cell line Sf9. In addition, a truncated, secreted form lacking the transmembrane and cytoplasmic domains (gp50T), was expressed in CHO and Sf9 cells. The protein, both in intact and truncated form, synthesized by the two mammalian cells contained only the disaccharide Gal beta 1-3GalNAc, either unsubstituted or substituted with one or two sialic acid residues. By contrast, the major O-linked structure on gp50 and gp50T synthesized by Sf9 cells was the monosaccharide GalNAc. The Sf9 cells also linked lower amounts of Gal beta 1-3GalNAc to gp50 (12%) and gp50T (26%). None of the structures synthesized by Sf9 cells contained sialic acid. Measurements of the two relevant glycosyltransferases revealed that while all three cell lines contain comparable levels of UDP-GalNAc:polypeptide, N acetylgalactosaminyltransferase activity, there is a greater variation in the levels of UDP-Gal:N-acetylgalactosamine, beta 1-3 galactosyltransferase, with the Sf9 cells containing the lowest level. PMID- 2112134 TI - Influence of extracellular calcium on cell permeabilization and growth regulation by the lymphokine leukoregulin. AB - Permeablization of human K562 leukemia cells was measured in the presence and absence of extracellular ionic calcium to examine the relationship of ionic calcium to increased membrane permeability and the inhibition of cell proliferation by this lymphokine. In the absence of extracellular calcium, the ability of leukoregulin to permeabilize the cell membrane is diminished but is fully restored by addition of 1 mM extracellular Ca++ as shown flow cytometrically by loss of intracellular fluorescein. Membrane permeability is also increased by calcium ionophore A23187 but permeablization is completely blocked in calcium-free medium despite the intramembrane presence of the calcium ionophore. Membrane permeablization by the lectin phytohemagglutinin, in contrast, is independent of extracellular calcium. A similar divergence in cell proliferation activity of the three modulators of calcium flux and membrane permeability occurs in the absence of extracellular calcium. Leukoregulin inhibition of cell proliferation is abolished, inhibition by calcium ionophore A23817 is greatly reduced, and inhibition by phytohemagglutinin is unchanged. Leukoregulin permeabilized K562 cells isolated by fluorescence activated cell sorting resume proliferation after 72 h. In contrast cells permeablized by calcium ionophore A23187 or phytohemagglutinin fail to resume proliferation by 7 days. The membrane permeablizing action of leukoregulin is, therefore, partially dependent upon extracellular calcium. It is also effected through a mechanism other than calcium ionophore transport or lectin type transmembrane signaling, and is accompanied by a reversible inhibition of cell proliferation. PMID- 2112135 TI - Positron emission tomographic measurements of cerebral glucose utilization using [1-11C]D-glucose. AB - Regional CMRglc was measured in seven healthy volunteers with positron emission tomography using [1-11C]D-glucose. Regional CBF was measured using [11C]fluoromethane. The arteriovenous differences of unlabeled glucose and oxygen together with 11C metabolites were also measured. In addition to the loss of [11C]CO2, a loss of acidic 11C metabolites was also detected. A three-compartment model was applied to the tracer data in the time interval 0-24 min. After correction for the loss of 11C metabolites, the tracer method gave an average CMRglc of 26.4 +/- 1.9 (SD) mumol/100 g/min, close to the value obtained with the Fick principle. After correction for the loss of [11C]CO2 only, the tracer method gave 23.6 +/- 2.1 mumol/100 g/min, compatible with (1/6) CMRO2, obtained with the Fick principle. These results and the time course of the loss of acidic 11C metabolites are consistent with the presence of nonoxidative metabolism of glucose that causes an early loss of mainly [11C]lactate after a bolus injection of the tracer. This implies that [1-11C]D-glucose measures the rate of glucose oxidation rather than the total CMRglc. The experiments using [1-11C]D-glucose were compared to five analogous experiments using [U-11C]D-glucose together with [15O]H2O as a flow tracer. After correction for the loss of [11C]CO2, the two glucose tracers gave similar global values of CMRglc and other parameters associated with glucose utilization, but with labeling in the carbon-1 position, the loss of [11C]CO2 was substantially delayed and the contrast between gray and white matter was improved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112136 TI - Metabolic and hemodynamic activation of postischemic rat brain by cortical spreading depression. AB - Following transient ischemia of the brain, the coupling between somatosensory activation and the hemodynamic-metabolic response is abolished for a certain period despite the partial recovery of somatosensory evoked responses. To determine whether this disturbance is due to alterations of the stimulus-induced neuronal excitation or to a breakdown of the coupling mechanisms, cortical spreading depression was used as a metabolic stimulus in rats before and after ischemia. Adult rats were subjected to 30 min of global forebrain ischemia and 3 6 h of recirculation. EEG, cortical direct current (DC) potential, and laser Doppler flow were continuously recorded. Local CBF (LCBF), local CMRglc (LCMRglc), regional tissue contents of ATP, glucose, and lactate, and regional pH were determined by quantitative autoradiography, substrate-induced bioluminescence, and fluorometry. Amplitude and frequency of the DC shifts did not differ between groups. In control animals, spreading depression induced a 77% rise in cortical glucose consumption, a 66% rise in lactate content, and a drop in tissue pH of 0.3 unit. ATP and glucose contents were not depleted. During the passage of DC shifts, transient increases (less than 2 min) in laser-Doppler flow were observed, followed by a post-spreading depression hypoperfusion. A comparable although less expressed pattern of hemodynamic and metabolic changes was observed in the postischemic rats. Although baseline LCMRglc was depressed after ischemia, it was activated 47% during spreading depression. Lactate increased by 26%, pH decreased by 0.3 unit, and ATP and glucose remained unchanged. The extent of the transient increase in laser-Doppler flow did not differ from that of the control group, and a post-spreading depression hypoperfusion was also found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112137 TI - Our priorities and our standards. PMID- 2112138 TI - Chronic renal failure in an obese adolescent. PMID- 2112139 TI - 'The oath'. PMID- 2112140 TI - Congressional blow against residents. PMID- 2112141 TI - GI bleeding four years after vascular surgery. PMID- 2112142 TI - ECMO indications and complications. AB - Widely adopted while prospective validation was still under way, extracorporeal membrane oxygenation is now a clinically established treatment for reversing neonatal respiratory failure. The technique's accomplishments are impressive-83% survival in conditions otherwise associated with 80% mortality-but its problems include significant handicap in 20% of treated survivors. PMID- 2112143 TI - Diagnosis and management of pheochromocytoma. AB - The diverse manifestations of this tumor reflect variations in the hormones it releases and their patterns of release and in the individual-to-individual differences in catecholamine sensitivities. There is relatively little correlation between circulating levels of the catecholamines and the extent or even existence of hypertension in these patients. An unusual case starts the discussion. PMID- 2112144 TI - Evaluation of hematochezia. AB - Although etiologies are diverse, diagnosis can usually be made with a careful history and physical examination, plus selected radiographic or endoscopic studies. Colonoscopy also sometimes allows prompt, definitive therapy. PMID- 2112145 TI - Searching for solutions. PMID- 2112146 TI - LDL cholesterol: its regulation and manipulation. AB - Elevated plasma LDL cholesterol concentrations result primarily from two mechanisms: LDL overproduction and loss of hepatic receptor-dependent LDL removal. This knowledge can be used to lower plasma cholesterol and thereby retard or even reverse atherosclerosis. Pharmacologic agents are useful, as are dietary approaches. PMID- 2112147 TI - Usual or unusual arrhythmia in acute myocardial infarction? PMID- 2112148 TI - Histoplasmosis. Recognition and treatment. PMID- 2112149 TI - The use of ELISA for detection of the antibody-induced conformational change in a viral protein and its intermolecular spread. AB - Antibody-induced conformational changes of proteins have been recently frequently suggested to explain a variety of observations. In spite of the fundamental importance of this phenomenon for both in vivo and in vitro antigen-antibody interactions, it is not generally accepted because of the lack of conclusive evidence. This report utilizes a novel approach to the study of antibody-induced antigenic conformational changes. Pairs of monoclonal antibodies (mAb) were used to induce and to assess conformational changes in potato virus X (PVX) protein. Blocking ELISA with native and glutaraldehyde treated virus was used to detect conformational changes. Double antibody sandwich (DAS) ELISA was designed to investigate possible inter-molecular spread of conformational changes. Detection of one way blocking in a blocking ELISA, with a pair of mAbs reacting to non overlapping epitopes, suggested conformational change as the mechanism of blocking. The putative conformational change was confirmed when the one way blocking was prevented using conformationally restrained virus. Inter-molecular spread of the conformational change among the molecules of PVX protein was demonstrated in DAS-ELISA, when capture mAb inhibited binding of detecting mAb in the absence of steric hindrance. Unlike X-ray crystallography, the methodology utilized in this study indicates directly the significance of a changed conformation to antibody binding. PMID- 2112150 TI - Decreased prolactin secretion by explant cultures of fibroids from women treated with a gonadotropin-releasing hormone agonist. AB - Endometrium, myometrium and uterine leiomyomata (fibroids) all secrete PRL. Although the regulation of endometrial PRL secretion has been extensively studied, little is known about myometrial and fibroid PRL. This study investigated the effects of the GnRH agonist (GnRH-a) leuprolide acetate depot, administered in vivo, on fibroid and myometrial PRL secretion by explant cultures. Tissue was obtained from 17 patients enrolled in a prospective, randomized, double-blind, placebo-controlled clinical trial. Explant cultures of fibroid and myometrium were established in defined serum free media and harvested media assayed for PRL and total protein. Fibroid PRL secretion was substantially greater than myometrial PRL secretion. Fibroid PRL secretion increased with time whereas myometrial PRL secretion did not. Fibroid, but not myometrial, PRL secretion in GnRH-a treated patients was significantly lower when compared to controls. Fibroid protein secretion was not affected by GnRH-a administration in vivo. Progesterone supplementation in vitro inhibited fibroid PRL secretion; estrogen and GnRH-a in vitro had a minimal effect. Western blot analysis showed a small proportion of PRL secreted by fibroids to be glycosylated. These results demonstrate: 1) PRL secretion is greater from fibroids than myometrium; 2) fibroid PRL secretion in vitro is specifically reduced after 24 h after in vivo treatment with GnRH-a; 3) estrogen or progesterone in vitro does not reverse the suppression by in vivo administration of GnRH-a; and 4) GnRH-a in vitro has no effect on fibroid PRL secretion. PMID- 2112151 TI - Iodine-induced hypothyroidism in euthyroid subjects with a previous episode of subacute thyroiditis. AB - The effects of the administration of pharmacological quantities of iodide on thyroid function in 18 euthyroid patients with a previous history of painful subacute thyroiditis (SAT) were evaluated, and the results compared to those of iodide administration to 12 euthyroid patients with a previous history of thyroid surgery (TX) for benign nodular thyroid disease. After baseline thyroid function tests, saturated solution of potassium iodide (SSKI; 10 drops; 300 mg iodide) was administered daily for 120 days, and serum T4, T3, and TSH concentrations were assessed 15, 30, 60, 90, 120 days and 2-4 months after SSKI was discontinued. Iodide perchlorate discharge tests were carried out before SSKI administration, and TRH tests were performed on the last day of iodide administration. Two SAT subjects developed clinical evidence of hypothyroidism with markedly elevated serum TSH concentrations, and SSKI was discontinued on days 60 and 90, respectively. Thirteen of 18 SAT patients had at least 1 abnormal thyroid function test (iodide perchlorate discharge test, elevated serum TSH concentration, and abnormal TSH response to TRH) compared to 2 of 12 TX patients. These findings strongly suggest that euthyroid subjects with a previous history of SAT are prone to develop iodide-induced hypothyroidism, suggesting that subtle abnormalities in the thyroid organification of iodide and subsequent thyroid hormone synthesis persist years after the episode of SAT. PMID- 2112152 TI - Inhibition of 125I organification and thyroid hormone release by interleukin-1, tumor necrosis factor-alpha, and interferon-gamma in human thyrocytes in suspension culture. AB - To elucidate the mechanism of decreased 131I uptake by the thyroid gland in patients with subacute thyroiditis and painless thyroiditis, human thyroid follicles were cultured with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and/or interferon-gamma (IFN gamma), and the effects of these cytokines on thyroid function were studied in vitro. When human thyrocytes were cultured in RPMI-1640 medium containing 0.5% fetal calf serum and TSH for 5-8 days, the cells incorporated 125I, synthesized de novo [125I]iodotyrosines and [125I]iodothyronines, and secreted [125I]T4 and [125I]T3 into the medium. IL-1 alpha and IL-1 beta inhibited 125I incorporation and [125I]iodothyronine release in a concentration-dependent manner. The minimal inhibitory effect was detected at 10 pg/ml. Electron microscopic examination revealed a marked decrease in lysosome formation in IL-1-treated thyrocytes. TNF alpha and IFN gamma also inhibited thyroid function in a concentration-dependent manner. Furthermore, when thyrocytes were cultured with IL-1, TNF alpha and IFN gamma, these cytokines more than additively inhibited thyroid function. Although the main mechanism of 131I uptake suppression in the thyroid gland in subacute thyroiditis is due to cellular damage and suppression of TSH release, our present findings suggest that IL-1, TNF alpha, and IFN gamma produced in the inflammatory process within the thyroid gland further inhibit iodine incorporation and at least partly account for the decreased 131I uptake by the thyroid gland in destruction-induced hyperthyroidism. PMID- 2112153 TI - Hypothyroidism and deficiency of the nocturnal thyrotropin surge in children with hypothalamic-pituitary disorders. AB - The circadian pattern of serum TSH in normal children, aged 5-18 yr, is characterized by a nocturnal surge and is presumably related in some way to a biological clock within the central nervous system. To look for patients deficient in the nocturnal TSH surge, we studied 52 children with hypothalamic pituitary disorders. Thirteen of the children were hypothyroid, as judged by subnormal serum free T4 (FT4). The hypothyroid patients had a mean nocturnal TSH surge of 22% (range, -30% to +114%), significantly less than that of normal controls (mean, 124%; 95% confidence limits, 47-300%; n = 96; P less than 0.01). Only 1 of the hypothyroid children had a value for the nocturnal TSH surge (114%) that was within the normal range. Nineteen of the 52 patients with hypothalamic pituitary disorders had subnormal nocturnal TSH surges; their mean iodothyronine values were significantly less than those of the 33 patients with normal surges [total T4, 73 +/- 4 (mean +/- SE) vs. 109 +/- 3 nmol/L (P less than 0.01); FT4, 13 +/- 1.0 vs. 19 +/- 0.5 pmol/L (P less than 0.01)]. These data demonstrate a clear association of a deficient nocturnal TSH surge and low iodothyronine concentration in children with hypothalamic-pituitary disorders. We performed both TRH tests and nocturnal TSH surge tests in 11 of the children with central hypothyroidism; TRH was abnormal in only 2, while the nocturnal surge test was abnormal in 10 of the 11. We suggest that the nocturnal surge of TSH is important for maintenance of thyroid function and conclude that the nocturnal TSH surge is a much more sensitive test than the TSH response to TRH for the diagnosis of central hypothyroidism. PMID- 2112154 TI - Cytokine regulation of antigen-driven immunoglobulin production in filarial parasite infections in humans. AB - To define the immunoregulatory mechanisms underlying serum IgE levels found in patients with filariasis, we studied polyclonal IgE production by peripheral blood mononuclear cells (PBMC) from 15 patients with filarial infections, with a focus on the role of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in the generation and regulation of the response. Spontaneous in vitro IgE production was elevated in 10 of the 15 patients (836-6,464 pg/ml; normals, less than 500 pg/ml). Addition of filarial parasite antigen to PBMC cultures significantly stimulated polyclonal IgE production in an antigen dose-dependent manner in 10 of 12 patients tested (P less than 0.001). The essential role of IL-4 in the generation of this response was demonstrated when simultaneous addition of anti IL-4 completely inhibited antigen-stimulated IgE production in all 10 patients studied. An inhibitory role of endogenously produced IFN-gamma was also indicated when the addition of anti-IFN-gamma to the cultures significantly augmented filarial antigen-stimulated IgE production by 33-1,238% in these same patients. Addition of 10-1,000 U/ml of recombinant human IFN-gamma to PBMC completely inhibited parasite antigen-induced IgE production. This study demonstrates that filarial antigen-stimulated IgE production in patients with filariasis is mediated by IL-4 and down regulated by IFN-gamma and suggests that the amount of IgE produced depends on the relative quantity of IL-4 and IFN-gamma generated by parasite-specific T cells. PMID- 2112155 TI - Defects in the E2 lipoyl transacetylase and the X-lipoyl containing component of the pyruvate dehydrogenase complex in patients with lactic acidemia. AB - Three patients with chronic lacticacidemia and deficiency of the pyruvate dehydrogenase complex demonstrated in cultured skin fibroblasts showed abnormalities on Western blotting with anti-pyruvate dehydrogenase complex antiserum which were not located in the E1 (alpha and beta) component of the complex. One of these patients had an enzymatically demonstrable deficiency in the E2 dihydrolipoyl transacetylase segment of the complex and very low observable E2 protein component on Western blotting of fibroblast proteins. The other two patients had abnormalities observable in the X component but no observable reduction in either E1, E2, or E3 enzymatic activities. One patient appeared to have a missing X component while the other had two distinct bands where X should be on Western blotting of fibroblast proteins. All three patients appeared to have severe clinical sequelae resulting from these defects. This is the first time that defects in either the E2 or the X component of the pyruvate dehydrogenase complex have been observed in the human population. PMID- 2112156 TI - A conserved idiotype and antibodies to retroviral proteins in systemic lupus erythematosus. AB - 22 of 61 systemic lupus erythematosus (SLE) patients produced antibodies to the p24 gag protein of HIV-1 demonstrated by Western blotting. 20 of these 22 patients (91%) also express the 4B4 idiotype (Id 4B4) previously identified on a human anti-Sm monoclonal antibody called 4B4. This represents an enrichment for this Id (seen in only 52% of SLE patients generally). Eight of these 22 SLE patients also have anti-Sm antibody activity. Sm partially inhibits the antibody binding of p24 gag suggesting immunologic cross-reactivity between the retroviral antigen p24 gag and the autoantigen Sm. Anti-Id 4B4 also inhibits p24 gag antibody binding by as much as 40%. Finally the monoclonal antibody 4B4 showed cross-reactivity to Sm and p24 gag. The following points emerge from our studies: (a) SLE patients make antibodies to p24 gag of HIV-1, (b) there is a relationship between immunity to p24 gag and a conserved idiotype, and (c) anti-Sm antibodies can cross-react with p24 gag. PMID- 2112158 TI - Structural model of porcine factor VIII and factor VIIIa molecules based on scanning transmission electron microscope (STEM) images and STEM mass analysis. AB - Porcine plasma factor VIII (fVIII) molecules are heterodimers composed of a 76,000-mol wt light chain (-A3-C1-C2) and a heavy chain ranging in molecular weight from 82,000 (A1-A2) to 166,000 (A1-A2-B). Proteolytic activation of fVIII by thrombin results in fVIIIa heterotrimers lacking B domains (A1, A2, A3-C1-C2). In this study, immunoaffinity purified fVIII was further fractionated by mono S or mono Q chromatography to prepare heterodimers containing a light chain and an A1-A2-B heavy chain (fVIII 166/76) or an A1-A2 heavy chain (fVIII 82/76). Mass analysis of scanning transmission electron microscopic (STEM) images of fVIII 166/76 indicated that heterodimers (mass 237 +/- 20 kD) had irregularly globular core structures 10-12 nm across, and frequently displayed a diffuse, occasionally globular to ovoid satellite structure extending 5-14 nm from the core, and attached to it by a thin stalk. Factor VIII 82/76 molecules (mass 176 +/- 20 kD) had the same core structures as fVIII 166/76 molecules, but lacked the satellite structure. These findings indicate that A1-A2 domains of heavy chains and the light chains of the fVIII procofactor molecule are closely associated and constitute the globular core structure, whereas the B domainal portion of heavy chains comprises the peripheral satellite appendage. Factor VIII core structures commonly displayed a finger-like projection near the origin of the B domainal stalk that was also a consistent feature of the free heavy chains (mass 128-162 kD) found in fVIII 166/76 preparations. Factor VIII light chain monomers (mass, 76 +/- 16 kD) were globular to c-shaped particles 6-8 nm across. These chains commonly possessed a v-shaped projection originating from its middle region, that could also be observed at the periphery of fVIII core molecules. Factor VIIIa preparations contained heterotrimers (mass 162 +/- 13 kD) that had the same dimensions as fVIII core structures, lacked the B domainal appendage, and sometimes possessed the same core features as fVIII molecules. Molecular species corresponding to heterodimers (mass, 128 +/- 13 kD) and unassociated subunit chains (40-100 kD) were also observed in fVIIIa preparations, suggesting that heterotrimers have an appreciable tendency to dissociate, a phenomenon that could explain the decay of fVIIIa activity after thrombin activation of fVIII. PMID- 2112157 TI - Modulation of in vitro monocyte cytokine responses to Leishmania donovani. Interferon-gamma prevents parasite-induced inhibition of interleukin 1 production and primes monocytes to respond to Leishmania by producing both tumor necrosis factor-alpha and interleukin 1. AB - Cytokines produced by mononuclear cells are important regulatory and effector molecules and evidence has been presented to support a role at least for tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in host defense against Leishmania. In the present study, we examined the production of TNF-alpha and interleukin 1 (IL-1) by resting and IFN-gamma-primed peripheral blood monocytes infected in vitro with Leishmania donovani. Monocytes produced neither IL-1 nor TNF-alpha during challenge with Leishmania. Cells preinfected with Leishmania synthesized normal amounts of TNF-alpha, but had diminished production of IL-1 in response to stimulation with either S. aureus or lipopolysaccharide (LPS). The induction by S. aureus or LPS of IL-1 beta mRNA accumulation in infected cells was normal despite diminished intracellular or supernatant IL-1 protein and bioactivity. Thus, inhibition of IL-1 production by Leishmania most probably reflected diminished translation of IL-1 beta mRNA. Pretreatment of cells with IFN-gamma abrogated infection-induced inhibition of IL 1 production and primed cells for the production of both IL-1 and TNF-alpha upon subsequent exposure to Leishmania. These results indicate that L. donovani has evolved the capacity to infect mononuclear phagocytes, without stimulating the production of two potentially host-protective monokines. The ability of IFN-gamma to prime monocytes to produce TNF-alpha and IL-1 in response to infection with Leishmania and to prevent inhibition of IL-1 production may have implications for immunotherapy with this lymphokine. PMID- 2112159 TI - Triiodothyronine uptake measurement in serum by time-resolved fluorescence immunofluorometry. AB - A solid phase competition-type fluoroimmunoassay for triiodothyronine (T3) uptake in serum is described. In the assay, exogenous free T3 binds to the unoccupied binding sites on serum thyroxine binding proteins while the remaining unbound T3 competes with immobilized T3 for binding to a soluble biotinylated anti-T3 monoclonal antibody. The bound biotinylated antibody is quantitated by the addition of streptavidin labeled with the europium chelator 4,7 bis(chlorosulfophenyl-1,10 phenanthroline-2,9-bicarboxylic acid (BCPDA) in the presence of excess europium. The fluorescence signal of the final complex, which is directly proportional to the number of unoccupied binding sites on thyroxine binding proteins, is then measured on the dried solid-phase with a pulsed-laser time-resolved fluorometer. The assay requires a 10 microliters serum sample and a total incubation time of 90 minutes. The coefficients of variation for within-run and between-run assays ranged from 2.0 to 5.7%. Results obtained by the present method compared well with those determined by two commercial radioimmunoassays (r greater than 0.9). PMID- 2112160 TI - Removal of residual luteinizing hormone by the use of a specific receptor and antibody coupled to glass beads. AB - We describe here, a novel and effective use of a specific receptor for Luteinizing Hormone (LH) coupled to controlled pore-glass beads (CPG) and LH antibodies to glass beads (GB), in selective removal of residual LH from purified Follicle Stimulating Hormone (FSH) and Thyroid Stimulating Hormone (TSH). The LH receptor was prepared from bovine corpora lutea. LH antisera were raised in rabbits and purified. FSH and TSH preparations were purified by treatment with the LH receptor coupled to CPG-beads; and/or LH-antibody coupled to glass beads. This procedure avoided dilution of the FSH or TSH during purification. PMID- 2112161 TI - Radioimmunoassay for bovine tumor necrosis factor: concentrations and circulating molecular forms in bovine plasma. AB - Antisera against recombinant bovine tumor necrosis factor (rbTNF) were produced in rabbits immunized with rbTNF in Freund's complete adjuvant (F314) and used in a double antibody radioimmunoassay to measure plasma TNF. Assay standards were rbTNF. Iodination of rbTNF and chromatography on G-50 Sephadex with 50 mM EDTA, 0.1% BSA, 0.05 M phosphate buffer, pH 7.5 resulted in labelled rbTNF which was greater than 97% TCA precipitable (specific activity of 37.5 microCi/micrograms). F314 (1:80,000 dilution) bound 21% of 125I-rbTNF in a non-equilibrium assay at 4 C. Separation of bound and free 125I-rbTNF was accomplished by precipitation with goat anti-rabbit IgG prepared with 6% polyethyleneglycol (mw = 8000). Minimum detectable TNF was 4 pg/assay tube. Matrix effects of plasma were minimal. Recovery of rbTNF from plasma was linearly (recovered TNF = .932 * added TNF = .12; r = .99). Displacement curves of increasing amounts of plasma from calves challenged with endotoxin to effect an increase in endogenous TNF were parallel to the rbTNF standard curve. F314 failed to crossreact with any other cytokines tested except human TNF (less than 1%). Neither recombinant nor native bovine TNF significantly interacted with antisera for TNF of human or murine origin. Plasma TNF was acutely elevated in calves infused with endotoxin. Changes in plasma TNF were determined in samples from calves with chronic parasitic infection. Endogenous plasma TNF existed as a monomer with a molecular weight of 17,000, and was not bound to any plasma carrier protein. These data indicate that a specific RIA for bTNF capable of detecting changes in in vivo TNF levels has been established. PMID- 2112162 TI - Adverse dermatologic reactions to transdermal drug delivery systems. AB - Transdermal drug delivery systems are marketed in the United States for four different drugs, and others are in various stages of development. Cutaneous side effects occur frequently with these systems and sometimes necessitate discontinuation of therapy. This article will review these adverse reactions. PMID- 2112163 TI - Antimicrobial therapy for cutaneous infections. PMID- 2112164 TI - The clinical development of mupirocin. AB - Mupirocin is a novel antibiotic totally unrelated in chemical structure and mode of action to any other clinically useful class of antibiotics. It has greatest antibacterial activity against aerobic gram-positive cocci, namely, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, and other beta-hemolytic streptococci. Bactroban ointment is formulated as 2% mupirocin in polyethylene glycol ointment. No systemic absorption of mupirocin or its major metabolite, monic acid, has been detected in short courses of topical administration to healthy volunteers or to patients with epidermolysis bullosa after prolonged courses of therapy with Bactroban ointment. Randomized, multicenter, double-blind, vehicle-controlled clinical trials have shown that mupirocin is safe and effective for the treatment of impetigo. PMID- 2112165 TI - Mupirocin: a new topical antibiotic. AB - One hundred fifty-three strains of Staphylococcus aureus recovered from infected eczema frequently demonstrated resistance to multiple antibiotics. Penicillin and ampicillin resistance was extremely frequent (88%), methicillin resistance was found in nearly 14% of strains, and erythromycin and tetracycline resistance was present in 16%. S. aureus strains were uniformly sensitive to vancomycin, mupirocin, and cephalosporins. Experimental infections in human volunteers showed topical therapy with 2% mupirocin was more effective than oral erythromycin in suppression of both S. aureus and Streptococcus pyogenes. PMID- 2112166 TI - A bacteriologically controlled, randomized study comparing the efficacy of 2% mupirocin ointment (Bactroban) with oral erythromycin in the treatment of patients with impetigo. AB - Sixty patients participated in a bacteriologically controlled, randomized, parallel group comparison of 2% mupirocin ointment (Bactroban) and oral erythromycin ethylsuccinate for the treatment of impetigo. The trial included clinical and bacteriologic evidence and safety assessments. The Investigator's Global Evaluation, which compared the overall efficacy and safety of the trial drugs, demonstrated a more favorable performance for the mupirocin regimen. This difference was statistically and clinically significant. There were no significant differences between the trial regimens for any of the other efficacy variables examined. The bacteriologic success rate was 100% for both treatment groups. There was a clinically significant difference in adverse experience rates between treatment groups, with four (13%) of the erythromycin-treated patients reporting six adverse experiences versus none of the mupirocin-treated patients. The results of the trial indicate that 2% mupirocin ointment is as safe and effective as oral erythromycin ethylsuccinate in the treatment of patients with impetigo. PMID- 2112167 TI - Use of mupirocin ointment in the treatment of secondarily infected dermatoses. AB - A double-blind, randomized, vehicle-controlled study was conducted to evaluate the safety and efficacy of 2% mupirocin ointment in the treatment of secondarily infected dermatoses. One hundred six patients were enrolled, 92 of whom were evaluable for efficacy. There was a significantly greater rate of eradication of Staphylococcus aureus and total pathogens in mupirocin-treated patients than in control subjects. Analysis of the clinical data relative to all pathogens showed a significant difference in skin infection evaluations performed at the interim and follow-up visits, which favored the mupirocin-treated groups. In those patients infected with S. aureus or Streptococcus pyogenes, there was a significant difference at end-point that favored mupirocin in seven clinical ratings and the skin infection evaluation at follow-up. Mild local adverse effects were noted in a small percentage of patients in each group. Mupirocin appears to be safe and effective for the treatment of secondarily infected dermatoses, especially in those infections caused by Staphylococcus aureus. PMID- 2112168 TI - Mupirocin-resistant Staphylococcus aureus after long-term treatment of patients with epidermolysis bullosa. AB - In a long-term, open study, 47 patients with epidermolysis bullosa were treated with topical 2% mupirocin (Bactroban) ointment to decrease bacterial infection and promote wound healing. This antibiotic is effective against gram-positive but not gram-negative organisms. No significant adverse effects were noted, although some patients have been treated for more than 4 years. We sought evidence in this patient population for the appearance of bacterial strains with decreased sensitivity to mupirocin. In five patients cultures from nonhealing wounds revealed Staphylococcus aureus resistance to mupirocin. Four of these patients were given oral antibiotics to which S. aureus was sensitive; they improved clinically, and cultures of their wounds became negative for pathogens. PMID- 2112169 TI - NCLEX-RN preparation: enabling candidates to pass. PMID- 2112170 TI - Compliance with mandatory continuing education in nursing: a hospital-based study. AB - The purpose of this study, which was conducted in a teaching hospital in northern New York, was to evaluate staff nurse and head nurse (HN) compliance with employer mandated continuing education (CE). The hospital's CE policy for nurses required all nursing employees to attend any six CE or inservice education programs per evaluation year. Staff nurse and HN sample groups were studied. The results revealed that 79% of the staff RN sample and 100% of the HN sample complied with employer requirements. The staff RNs attended an average of 13 programs per year, and the HNs averaged 16 programs per year. When comparing these averages to the actual number required, the assumption can be made that nurses attend CE programs for reasons other than complying with requirements. PMID- 2112171 TI - Inservice education: calculating the cost. AB - Cost effectiveness is the mandate in healthcare today. Nursing staff development especially has needed to rethink its methodologies because of the significant cost of programs. The Department of Nursing Education and Resources of Miami Valley Hospital in Dayton, Ohio adopted an "All-Day" concept in an effort to achieve maximum efficiency from its resources for inservice education. To comprehensively and accurately determine how efficient the all-day method was in terms of cost in comparison with the previous "unit-based" process, a detailed cost analysis was undertaken. Each method was studied for 1 year, and the comparison revealed the all-day method was more viable from a cost perspective, as well as more beneficial from the participants' perspective. PMID- 2112172 TI - Communication skills for continuing education in nursing. AB - Good communication is a vital element in the delivery of quality nursing care, while poor communication can lead to lawsuits and avoidable patient death. This research surveyed 132 hospital nurses in the Midwest to determine their communication education while in school, the availability of continuing education programs related to communication, and the most important communication skills in nursing. The results indicate a great need for inservice education on communication. PMID- 2112173 TI - Using mental imagery to practice a specific psychomotor skill. AB - This study explored the usefulness of mental imagery as a technique for practicing psychomotor nursing skills. Using the specific skill of one-rescuer cardiopulmonary resuscitation (ORCPR) and a control group, several posttest questions addressed mental imagery and the possible improvement of performance proficiency with its use. The findings suggested that subjects were able to clearly perceive a specific psychomotor skill using mental imagery (p = .05). The subjects in this study indicated that mental imagery was a useful and interesting learning technique. No significant differences were noted in the performance of the study and control groups. PMID- 2112174 TI - Evaluation of an inservice education program regarding aggressive behavior on a psychiatric unit. AB - A four-part inservice program on dealing with aggressive behavior on a psychiatric unit was developed, presented, and evaluated. The program was aimed at meeting staff members' cognitive, emotional, and psychomotor needs. Twenty seven staff members participated. The program was successful in reducing extreme levels of burnout among staff members, and occurrences of patient aggressive behavior resulting in incidents declined after the program. Staff members reported that they felt more confident in dealing with aggression. Protocols and nursing care plans were developed, and ongoing support groups to examine staff members' feelings were established. PMID- 2112175 TI - Evaluation of nursing documentation of patient teaching. AB - The preprinted interdisciplinary care plan is an effective tool in increasing the documentation of patient teaching onto the patient education record; however, when combined with praise and chart audits, the preprinted document becomes even more effective. This study indicates that reinforcement in the form of a preprinted care plan combined with inservice education and audit increases documentation of patient education more than the use of the preprinted document alone. PMID- 2112176 TI - Relationship between sources of knowledge and use of research findings. PMID- 2112177 TI - Reversal of midazolam sedation with flumazenil following conservative dentistry. AB - The purpose of this double-blind randomized study was to assess recovery of mental function following reversal of midazolam-induced sedation with the specific antagonist flumazenil (R015-1788) or placebo following conservative dental procedures. Recovery was assessed using choice reaction time and critical flicker fusion threshold, both objective tests of psychomotor function; linear analogue sedation scores and simple memory tests. Assessments were repeated up to 3 h after administration of flumazenil or placebo to discover whether recovery was sustained or whether resedation occurred due to the short duration of action of flumazenil. Flumazenil in doses from 0.5 to 1.0 mg rapidly reversed the sedative and amnesic effects of a mean dose of 8.2 mg of midazolam without apparent evidence of subsequent resedation. Since recovery of mental function in the control group had ordinarily occurred 45 min after administration of placebo, routine reversal of midazolam sedation with flumazenil cannot be justified. Nevertheless, in cases of undue sedation persisting after dental treatment, flumazenil may be used with minimal risk of resedation occurring. PMID- 2112178 TI - Enterostomal therapy nurse justification. PMID- 2112179 TI - Lasers in dermatology. AB - A laser is a device that produces a parallel bundle of photons of equal wavelength that are temporally and spacially in phase. The laser light can be focused to produce high energy in very small spots. The pulsed dye laser, the argon laser and the carbon dioxide laser are commonly used in dermatology. The pulsed dye laser and the argon laser are especially effective for cutaneous vascular lesions such as port-wine hemangiomas. It is important for the physician to be knowledgeable about laser-tissue interaction and laser safety to avoid laser accidents. PMID- 2112180 TI - Thrombolytic therapy in acute coronary thrombosis. AB - Thrombolytic agents administered intravenously have been shown to have a salutary effect in the early management of acute myocardial infarction. However, a debate still is pending over the definite choice of an ideal thrombolytic agent. In our 83-bed community hospital, from January 1986 to September 1988, we treated 19 patients (n = 19) with acute myocardial infarction (average one patient every six weeks) with either intravenous streptokinase (IV STK) or intravenous tissue plasminogen (IV TPA) with a mean follow-up of 20.2 months. We compared both groups in terms of clinical reperfusion, morbidity and mortality, cost effectiveness and long-term functional disability. Our results showed that most patients received their respective agents within four hours of the onset of chest pain (81% in the STK group, n = 11, versus 75% of the tPA group, n = 8). In the STK group, 90.9% showed clinical evidence of reperfusion compared to 87.5% in the TPA one, the difference not being statistically significant. Two patients in the STK group developed a treatable bradycardia, and one showed a junctional rhythm that was corrected. One patient in the TPA subset encountered a reversible ventricular tachycardia. However, we didn't note any bleeding complication in either group. PMID- 2112181 TI - [Congenital esophagobronchial fistula communicated to esophageal diverticulum, report of a case]. AB - We encountered a successful repair of congenital esophagobronchial fistula communicated to esophageal diverticulum. A 35 year-old-female has had frequent episodes of pneumonia since her 1st delivery. Barium esophagogram revealed a fistulous tract between the esophageal diverticulum and the right lower lobe bronchus. Bronchogram showed a ectatic dilatation at B6a and B6c. The resection of diverticulum and right lower lobectomy including the removal of fistulous tract were carried out. Histological examination of the resected fistula revealed a smooth connection between squamous epithelium and columnar epithelium. And muscularis mucosa was maintained with no evidence of inflammatory changes. So this case was diagnosed a Braimbridge I type esophagobronchial fistula. In Japan 21 cases of congenital esophagobronchial fistula with diverticulum have been reported. It is assumed that three histological findings as mentioned above is important for the diagnosis of congenital esophagobronchial fistula. PMID- 2112182 TI - Enzymatic and immunological properties of alkaline phosphatase of bullfrog. AB - Enzymatic and immunological properties of alkaline phosphatase (ALPase) in several tissues of bullfrog (Rana catesbeiana) were investigated. Inhibition and thermal inactivation studies showed that bullfrog ALPases in kidney, liver, and intestine had similar enzymatic properties. In addition, mouse antiserum against bullfrog liver ALPase cross-reacted with kidney and intestine enzymes as well as with liver enzyme. These results suggest that a single phenotype of ALPase exists in all tissues of bullfrog in contrast to two or three isoenzymes in mammals. PMID- 2112183 TI - Fluorouracil, doxorubicin, cyclophosphamide, and cisplatin combination chemotherapy in advanced or recurrent salivary gland carcinoma. AB - Seventeen patients with recurrent or unresectable salivary gland carcinomas were treated with combination fluorouracil (5-FU), doxorubicin, cyclophosphamide, and cisplatin (FACP). Sixteen patients were assessable for response and toxicity. A total of 111 courses of chemotherapy were given, yielding one complete and seven partial responses, for an objective response rate of 50%. Two other patients had stable disease and two had a minor response. The median duration of objective response was 32 weeks (range, 4 to 72); median survival for the 16 patients was 72 weeks. Hematologic toxicity was significant, with 88% developing a nadir granulocyte count of less than 1,000 cells per microliter (median, 300 cells per microliter), and 53% a nadir platelet count of less than 100,000 cells per microliter (median, 68,000 cells per microliter). Seven patients (44%) developed neutropenic fever, and three (18%) developed an increase in serum creatinine greater than 1.5 mg/dL during the course of treatment. This combination of chemotherapy was active; however, an increased response rate was not observed above that reported for other combinations. Response duration, or overall patient survival, on this intensive regimen was similar as compared with other published therapeutic trials of this disease entity. PMID- 2112184 TI - In vivo biological response to recombinant interferon-gamma during a phase I dose response trial in patients with metastatic melanoma. AB - Interferon-gamma (IFN gamma), as produced by recombinant DNA technology, has shown a wide range of immunomodulatory activity in vitro and in vivo. Clinical studies have attempted to establish a dose-response relationship to define optimal dosage ranges for induction of effector cell function and host response in patients with cancer. We conducted a randomized trial to test the in vivo biologic activity of five daily dosages ranging from 3 to 3,000 micrograms/m2, administered by daily 2-hour bolus injection or by continuous infusion for 14 days. We demonstrate comparable immunobiologic effects of recombinant IFN gamma (rIFN gamma; Biogen, Inc, Cambridge, MA) administered by these two schedules at the various dosages tested, and have defined a relationship of dose to biologic response over this 3-log10 dose range. Oligo 2'5' adenylate synthetase (2'5'As) induction, natural-killer (NK) cell activity, and T-cell subset distribution (heightened T helper/suppressor ratio) showed the most consistent treatment associated changes and the greatest immunobiologic effects at dosages of 300 to 1,000 micrograms/m2. Mononuclear cell DR and DQ antigen expression showed no consistent dose-related treatment effect. The relevance of the phenotypic, functional, and enzymologic effects observed in this trial to any clinical antitumor effects of IFN gamma in cancer therapy must now be established. PMID- 2112185 TI - In vivo traffic of indium-111-oxine labeled human lymphocytes collected by automated apheresis. AB - The in vivo traffic patterns of autologous lymphocytes were studied in five normal human volunteers using lymphocytes obtained by automated apheresis, separated on Ficoll-Hypaque gradients, and labeled ex vivo with 111In-oxine. Final lymphocyte infusions contained 1.8-3.1 X 10(9) cells and 270-390 microCi (9.99-14.43 MBq) 111In, or 11-17 microCi (0.41-0.63 MBq) per 10(8) lymphocytes. Gamma imaging showed transient lung uptake and significant retention of radioactivity in the liver and spleen. Progressive uptake of activity in normal, nonpalpable axillary and inguinal lymph nodes was seen from 24 to 96 hr. Accumulation of radioactivity also was demonstrated at the forearm skin test site, as well as in its associated epitrochlear and axillary lymph nodes, in a subject who had been tested for delayed hypersensitivity with tetanus toxoid. Indium-111-oxine labeled human lymphocytes may provide a useful tool for future studies of normal and abnormal lymphocyte traffic. PMID- 2112186 TI - Neurofibromatosis type 1 in childhood. PMID- 2112187 TI - A comparison of rice-based oral rehydration solution and "early feeding" for the treatment of acute diarrhea in infants. AB - To compare the use of rice-based oral rehydration solution (R-ORS), with the introduction of food immediately after rehydration ("early feeding"), using standard glucose-based oral rehydration solution (G-ORS) in the management of acute diarrhea, we conducted a four-cell randomized, controlled trial among 200 hospitalized Egyptian infants between 3 and 18 months of age. During the rehydration phase (first 4 hours), three groups were given G-ORS and a fourth group was given R-ORS. During the subsequent maintenance phase, the control group was given a soy-based, lactose-free formula (G-ORS + SF), a second group (G-ORS + RF) was given a rice-based formula, and a third group (G-ORS + rice) was given boiled rice. The fourth group (R-ORS + SF) continued to receive R-ORS for the first 24 hours of the maintenance period, followed by a soy-based lactose-free formula. During the first and second 24 hours of the maintenance period, infants in the three treatment groups had a lower mean stool output in comparison with the control group (p = 0.006 and 0.03, respectively). The mean total stool output in the R-ORS + SF group was significantly lower than in the control group (p = 0.02). There were no statistically significant differences among the four groups in the mean duration of diarrhea. We conclude that (1) infants who were given R ORS had reduced total stool output (by 35%) compared with the control group and (2) feeding of boiled rice or a rice-based formula immediately after rehydration therapy was as efficacious as treatment with R-ORS alone for 24 hours, followed by feeding with a soy-based, lactose-free formula. PMID- 2112188 TI - High-frequency oscillatory ventilation compared with conventional mechanical ventilation in the treatment of respiratory failure in preterm infants: assessment of pulmonary function at 9 months of corrected age. HiFi Study Group. AB - In a comparison of the outcome of high-frequency oscillatory ventilation (HFO) and conventional mechanical ventilation (intermittent mandatory ventilation (IMV] in newborn infants, the degree of late pulmonary damage in these infants was assessed in a multicenter trial by examining their pulmonary status, including pulmonary function test results at 9 months of corrected age. A total of 432 infants were followed, 222 in the IMV group and 210 in the HFO group. Two-hundred twenty-three infants had their pulmonary mechanics measured, 118 in the IMV group and 105 in the HFO group. There were no significant differences between the two groups in conditions known to predispose infants to chronic lung disease. At 9 months of age, both groups has similar growth and a similar incidence of respiratory tract infections and hospital readmissions, and of retractions and episodes of wheezing. None of the pulmonary mechanics measurements differed. Forced expiratory flow at functional residual capacity was decreased (132 +/- 86 vs 135 +/- 92 ml/sec in the IMV and HFO groups, respectively), peak-to-peak esophageal pressure change was elevated (14.4 +/- 5.7 vs 13.5 +/- 5.7 cm H2O), dynamic compliance was in the low normal range (1.2 +/- 0.5 vs 1.3 +/- 0.6 ml/cm H2O/kg), and total pulmonary resistance was elevated (63 +/- 43 vs 57 +/- 34 cm H2O/L/sec) when the measurements were compared with normal values. The results indicate that in both groups, 30% to 40% of infants survived with chronic pulmonary changes similar to those described in infants with bronchopulmonary dysplasia. The use of high-frequency ventilation, in comparison with IMV, did not improve long-term pulmonary outcome. PMID- 2112189 TI - Effect of indomethacin on superior mesenteric artery blood flow velocity in preterm infants. AB - In 15 preterm infants with symptomatic patent ductus arteriosus, blood flow velocity changes in the superior mesenteric artery were investigated with Doppler ultrasound just before and during the first 12 hours after a single dose of indomethacin. Indomethacin administration led to an instantaneous decrease in all infants of temporal mean flow velocity in the superior mesenteric artery, which was maximal 10 minutes after administration of indomethacin, followed by a more sustained recovery, slightly greater than baseline values, 12 hours after indomethacin treatment. Simultaneously determined temporal mean flow velocity of the anterior cerebral artery, used as an indicator of changes in cerebral blood flow, had a similar pattern as in the mean flow velocity in the superior mesenteric artery (r = 0.49; p less than 0.001). Our data suggest that indomethacin lowered blood supply to the bowel, similar to its action on cerebral blood flow. PMID- 2112190 TI - Recent patterns of drug use in newborn intensive care. AB - To better understand patterns of medication use in neonatal intensive care, we examined data collected prospectively over a recent 9-year period in the newborn intensive care units of two large teaching hospitals. Among 2690 infants studied, 91% received at least one drug; 99% of infants weighing less than 1500 gm were exposed to drugs, compared with 90% of infants weighing more than 1500 gm. Among treated infants, the median number of drugs received was eight; the number of drugs administered was inversely related to birth weight and directly related to both length of hospital stay and the complexity of the infant's clinical condition. Within categories of length of hospital stay, the number of drugs received per day was greatest during the first week in the neonatal intensive care unit and fell to a relatively stable lower level during the second week. The most commonly used single drug was gentamicin (71% exposed), followed by sodium chloride (60%), potassium chloride (59%), heparin (58%), and packed erythrocytes (45%). Between 1978-1979 and 1985-1986 the prevalence of use increased substantially for some drugs (ampicillin, morphine, calcium salts, and acetates of sodium and potassium) and decreased for others (kanamycin, sodium bicarbonate, and blood products). These data document the dynamic nature of drug therapy in the neonatal intensive care unit and provide information that can guide cost benefit assessments in this setting. PMID- 2112191 TI - Long-term colchicine prophylaxis in children with familial Mediterranean fever (recurrent hereditary polyserositis). PMID- 2112192 TI - Deficient activity of prostacyclin stimulating plasma factor (PSPF) in newborns. AB - The activity of PSPF was studied in 38 normal newborns. The production of 6-keto PGF1 (PGI2 stable metabolite) after stimulation with cord blood plasma, 0.72 +/- 0.50 pmol/10(5) cells, was lesser than after stimulation with plasma from 2-3 years old children, 3.00 +/- 0.89 pmol/10(5) cells (p less than 0.01), or from adults, 7.74 +/- 5.00 pmol/10(5) cells (p less than 0.001). No differences were shown during neonatal period. The presence of a circulating inhibitor factor in newborns was dismissed by mixed cultures. The behaviour of neonatal plasma after consecutive stimulations with AA was similar to adult plasma response. We proved that newborns show a deficient capacity to stimulate PGI2, which is not due to circulating inhibitor factor, and we think that this deficiency is due to a weaker action of stimuli, rather than to an immaturity. PMID- 2112193 TI - Cardiorespiratory effects induced by acetazolamide on the ventromedullary surface of the cat. AB - 1. Inhibition of carbonic anhydrase by acetazolamide in alpha-chloralose anaesthetized cats, in a region of the brain stem co-extensive with the glycine sensitive area, intermediate chemosensitive area, and probably C1 catecholaminergic neurones produces hypotension, bradycardia and depression of the central respiratory drive. 2. These responses are concentration dependent, and can still be observed when the enzyme substrate (CO2) is elevated. Therefore, in both the hypercapnic and the normocapnic condition, similar responses in arterial blood pressure, heart rate and respiratory rate are observed when acetazolamide is topically applied to the glycine-sensitive area. 3. To investigate further the contribution of peripheral baro-, chemo- and cardiopulmonary receptors to these responses, acetazolamide was topically applied to the glycine-sensitive area under three different conditions: intact gallamine paralysed (5 mg kg-1 h-1) and artificially ventilated (A), sinoaortic denervated (B), and sinoaortic denervated plus bilaterally vagotomized cats (C). Under all conditions, similar responses were observed. The fall in arterial blood pressure was 75 +/- 11 (A), 90 +/- 13 (B), and 75 +/- 9 mmHg (C). Changes in heart rate during acetazolamide application were -23 +/- 6, -20 +/- 8, and -26 +/- 6 beats min-1, respectively. The decreases in respiratory rate were 9 +/- 2 (A), 11 +/- 2 (B), and 11 +/- 2 breaths min-1 (C). 4. The data indicate that the responses to topical application of acetazolamide are mainly due to its central action at the glycine-sensitive area and are not influenced by peripheral baroreceptor and chemoreceptor inputs. PMID- 2112194 TI - Calcium dependency of the endothelium-dependent hyperpolarization in smooth muscle cells of the rabbit carotid artery. AB - 1. In smooth muscle cells of the rabbit carotid artery, ACh (greater than 10(-8) M) generated a hyperpolarization with two components (transient followed by sustained), only in the tissues with an intact endothelium. There were no detectable changes in the membrane potential, as elicited by ACh (up to 10(-5) M) in tissues with no endothelium or in the presence of atropine (10(-6) M). 2. Reduction of [Ca2+]o inhibited the sustained component which was not apparent in [Ca2+]o below 0.16 mM. In Ca2+-free (EGTA-containing) solution, the generation of the transient component of the hyperpolarization remained sustained but with a substantially reduced amplitude. 3. Procaine (greater than 10(-6) M) inhibited the ACh-induced hyperpolarization in a concentration-dependent manner, and at a concentration of procaine (10(-3) M) which caused substantial depolarization of the membrane, no detectable change was elicited by ACh. 4. Caffeine (10(-6)-10( 3) M) produced a transient hyperpolarization, independent of the presence or absence of the endothelium, and inhibited the sustained component of the ACh induced hyperpolarization more so than the initial component. 5. A23187 (greater than 10(-8) M) hyperpolarized the smooth muscle membrane in a concentration dependent manner, and this hyperpolarization was not generated in Ca2+-free solution or in the absence of endothelial cells. 6. In intact tissues, pre treatment with A23187 resulted in a reduction of the subsequently generated ACh induced hyperpolarization, in an irreversible manner. 7. It would thus appear that in the rabbit carotid artery, the endothelium-dependent hyperpolarization induced by ACh has Ca2+-dependent and Ca2+-independent components, and each may be related to the increase in endothelial [Ca2+]i by release from the intracellular store and by influx from the extracellular medium, respectively. The increased [Ca2+]i would trigger a release of an endothelium-derived hyperpolarizing factor (EDHF) from the endothelial cells. PMID- 2112195 TI - Membrane potential dependence of intracellular pH regulation by identified glial cells in the leech central nervous system. AB - 1. We have measured the intracellular pH (pHi) and membrane potential of identified glial cells in the central nervous system of the leech, Hirudo medicinalis, using double-barrelled pH-sensitive microelectrodes. 2. When extracellular K+ concentration was increased, the glial membrane potential decreased and pHi increased; lowering the extracellular K+ concentration hyperpolarized the glial membrane and decreased pHi. These pHi changes were largely dependent upon the presence of CO2-HCO3-; in nominally CO2-HCO3(-)-free saline solution, they were 50-80% smaller. 3. The steady-state pHi of the glial cells in CO2-HCO3(-)-buffered saline solution strongly correlated with the membrane potential between -40 and -90 mV. The slope of this relationship was 60 mV/pH unit. 4. The neurotransmitter 5-hydroxytryptamine (50 microM), which hyperpolarizes the glial membrane, also produced a large, CO2-HCO3(-)-dependent decrease in pHi. The size of the pHi change depended upon the amplitude of the membrane hyperpolarization. 5. The increase in pHi produced by the membrane depolarization in 20 mM-K+ was abolished in Na(+)-free saline. Removal of external Na+ in the presence of 20 mM-K+ reversed the pHi increase. 6. The pHi increase in 20 mM-K+ was also inhibited by the stilbene 4,4 diisothiocyanostilbene-2'-disulphonic acid (DIDS, 0.5 mM). In a DIDS-poisoned preparation a small decrease of pHi was observed in 20 mM-K+ both in the presence and nominal absence of CO2-HCO3-. 7. In neurones, neither CO2-HCO3- nor 20 mM-K+ produced an intracellular alkanization. The steady-state pHi of several identified neurones was not correlated with the membrane potential. 8. We conclude that in glial cells, but not in neurones, the pHi is dependent upon the membrane potential. This membrane potential dependence is due to the activity of the electrogenic Na(+)-HCO3- co-transporter in the glial cell membrane. PMID- 2112196 TI - Inhibitory effects of gold sodium thiomalate on the proliferation and interferon gamma induced HLA-DR expression in human endothelial cells. AB - Our study was undertaken to investigate the effects of gold sodium thiomalate (GSTM) on the proliferation and HLA-DR antigen expression of human umbilical vein endothelial cells (EC). The proliferation of the EC was determined by 3H thymidine incorporation into the EC. The expression of HLA-DR antigen on the surface of the EC was detected by an indirect immunofluorescent method using a fluorescent flow cytometer. When GSTM was added at the start of the EC culture, GSTM at a low concentration could inhibit the proliferative response of the EC to endothelial cell growth supplement. Furthermore, when the EC were cultured with recombinant interferon-gamma (rIFN-gamma) and GSTM, GSTM was also able to suppress the HLA-DR antigen expression on the surface of EC induced by rIFN gamma. On the time-kinetic study of the effects of GSTM on the HLA-DR antigen expression induced by rIFN-gamma, the pretreatment of GSTM was able to suppress the HLA-DR antigen expression, whereas GSTM did not affect the HLA-DR antigen expression already induced by rIFN-gamma. Our findings suggest that the therapeutic effects of gold compounds in patients with rheumatoid arthritis may be attributed to the interference of the proliferation and HLA-DR antigen expression of the EC. PMID- 2112197 TI - Inhibition of the passive transfer of adjuvant induced arthritis by gold sodium thiomalate. AB - The effect of gold on the passive transfer of adjuvant induced arthritis was studied to determine if gold acted in the donor and/or recipient arms of this model. Joint scores were markedly decreased in rats receiving spleen cells from donor animals treated with gold (p less than 0.01) suggesting that gold injections alters the development and/or function of the spleen cells from these animals which transfer adjuvant induced arthritis. Gold treatment of recipient animals had little effect on subsequent arthritis. PMID- 2112198 TI - Intraarticular pressure and the relationship between synovial perfusion and metabolic demand. AB - We examined the influence of intraarticular pressure on products of synovial energy metabolism in patients with knee effusions. A range of intraarticular pressures was generated by controlled flexion. Pressures greater than or equal to 45 mm Hg were associated with increased synovial fluid lactate concentrations and pCO2, and decreased pH. Our results suggest that pressures greater than or equal to 45 mm Hg, which we also observed during standing and walking, can cause synovial ischemia and hypoxia manifest in a perfusion/metabolic demand mismatch. Monitoring changes in SF concentrations of uric acid did not provide consistent evidence for accelerated purine degradation following periods of inadequate perfusion. Overall, our results suggest that synovial blood flow can be compromised by modest elevations in intraarticular pressure in the range encountered during daily activity in patients with knee effusions. PMID- 2112199 TI - Mycobacterial antigens stimulate rheumatoid mononuclear cells to cartilage proteoglycan depletion. AB - In a coculture with porcine articular cartilage explants unstimulated blood mononuclear cells (BMC) from patients with rheumatoid arthritis (RA), but not from healthy controls, induced proteoglycan depletion of dead cartilage. Specific stimulation of the RA BMC with Mycobacterium tuberculosis (MT), in comparison with concanavalin A (Con-A), strongly enhanced the proteoglycan depletion of living cartilage; this was not found with the BMC of healthy controls. However, the MT induced proliferative responses of the same BMC were similar in healthy controls and patients with RA. Neither the proliferative response nor the proteoglycan depletion was influenced by the presence of HLA-DR4 in the donor, whether patients with RA or healthy control. The proliferative responses of the RA BMC seemed to correlate inversely with the proteoglycan depletion. We conclude that stimulation of RA BMC with mycobacterial antigens may elicit effector pathways that induce proteoglycan depletion, independent of T cell proliferation. PMID- 2112200 TI - New carbon dioxide-independent basal growth medium for culture of diverse tumor and nontumor cells of human and nonhuman origin. AB - A eukaryotic growth medium (Program Development Research Group Basal Growth Medium) was developed for CO2-independent maintenance and propagation of human and nonhuman tumor cell lines representing diverse histologies (e.g., cancers of the brain, colon, lung, ovary, and kidney, as well as leukemia and melanoma). It was also shown to be suitable for the maintenance and propagation of nontumor cells of human and nonhuman derivation. The medium derives its buffering capacity primarily from beta-glycerophosphate, exhibits a stable physiologic pH of 7.3 7.4, and is optimized to facilitate growth in atmospheric CO2. It is also useful in cellular growth and cytotoxicity assays based on either the metabolic reduction of tetrazolium reagents or protein staining. The 50% inhibitory concentration values obtained with carmustine, doxorubicin, and tamoxifen in cell lines maintained in the new medium under atmospheric CO2 were closely comparable to those obtained with these drugs against cells maintained in RPMI-1640 under a 5% CO2 environment. PMID- 2112201 TI - Recombinant human interferon gamma: adverse effects in high-risk stage I and II cutaneous malignant melanoma. PMID- 2112202 TI - Metabolism and distribution of bromodichloromethane in rats after single and multiple oral doses. AB - The disposition of [14C]bromodichloromethane (BDCM) was studied in male Fischer rats after single oral doses of 1, 10, 32, or 100 mg/kg and 10-d repeat oral dosing of 10 or 100 mg/kg/d. Methods were developed to quantitate exhaled 14CO and 14CO2. Bromodichloromethane was extensively (approximately 80-90%) metabolized within 24 h postdosing with approximately 70-80% of the administered dose appearing as 14CO2 and approximately 3-5% as 14CO. Urinary and fecal elimination were low, accounting for 4-5% and 1-3% of the dose, respectively. Oral administration of BDCM at a level of 10 mg/kg/d for 10 d did not result in the bioaccumulation or altered disposition of the test chemical, but during the course of the repeat 100 mg/kg/d dosing the rate of production of 14CO2 increased, suggesting that this dose of BDCM induced its own metabolism. Persistence of radiolabeled residues in tissues collected 24 h after single-dose administration was low (3-4% of dose), with the most marked accumulation (1-3% of dose) in liver. Kidney tissue, particularly the cortical region, also contained significant concentrations of residues. PMID- 2112203 TI - Serological evidence of Crimean-Congo haemorrhagic fever viral infection among camels imported into Egypt. AB - A serosurvey was conducted during 1986-87 to determine evidence of prior Crimean Congo haemorrhagic fever (CCHF) viral infection among camels imported into Egypt from Sudan and Kenya. Sera obtained from camesl arriving at the Aswan quarantine station, southern Egypt, were tested for CCHF antibody by the agar gel diffusion (AGD) and the indirect fluorescent antibody (IFA) techniques. CCHF viral antibody was demonstrated in 14% (600/4301) of the camels, with both techniques yielding similar results. CCHF viral antibody prevalence among camels imported from Sudan was lower (12%) than among camels imported from Kenya (26%). Ganjam and Qalyub viral antibody was not detected among the 600 CCHF viral antibody positive sera, but 7% (44/600) were positive for Dugbe viral antibody. CCHF viral antibody was not demonstrated in 400 sheep and 200 cows of native animals. These data indicate that camels imported from Sudan and Kenya had previous CCHF viral infection, but evidence of transmission to animals of Egypt was not obtained. Further studies are needed to assess the possible role of imported animals in the ecology and epidemiology of CCHF virus in Egypt. PMID- 2112204 TI - Epidemic transmission of enterically transmitted non-A, non-B hepatitis in Mexico, 1986-1987. AB - Outbreaks of acute hepatitis occurred in Huitzililla and Telixtac, two rural villages 70 miles south of Mexico City, Mexico, in late 1986. The first outbreak began in Huitzililla in June of that year, 1 month after the start of the rainy season. A census revealed 94 icteric case subjects, for an attack rate of 5%; two women died. Attack rates were higher for persons older than 15 years (10%) than for younger persons. A case-control study showed that illness was highly associated with water-related factors. The second outbreak began in August 1986 in Telixtac. There were 129 case subjects, for an attack rate of 6%; one woman died. Epidemiologic findings were similar to those in Huitzililla, except that most disease transmission was not linked to unsafe water sources. None of 62 case subjects in Huitzililla and only 2 of 53 case subjects in Telixtac tested had serological evidence for recent infection with hepatitis A or B. Two of eight stool samples from Huitzililla and one of the eight stool samples from Telixtac were positive by immune electron microscopy for 32- to 34-nm viruslike particles similar to those seen in cases of enterically transmitted non-A, non-B hepatitis from Asia. To our knowledge, these investigations document for the first time the epidemic transmission of enterically transmitted non-A, non-B hepatitis virus in the Americas. PMID- 2112205 TI - [A clinical study of asymptomatic bacteriospermia]. AB - Asymptomatic bacteriospermia was studied as an entity and its treatment was investigated in 65 subjects who clinically needed their semen tested. The obtained results are summarized as follows. 1. The rate of detection of bacteria in semen was 89.2%, and the rates of detection of aerobic and anaerobic bacteria were 55.4% and 70.8%, respectively. Forty Gram-positive strains were identified among the aerobic bacteria; rates of detection for Staphylococcus epidermidis and Enterococcus faecalis were high, and 6 strains (9.2%) of Streptococcus agalactiae were also present. The rate of detection of Gram-negative bacteria was low; only 3 strains were identified. Among the anaerobic bacteria 90 Gram-positive strains were identified; the rate of detection of Peptostreptococcus (58 strains) was high, and only 11 strains of Gram-negative bacteria were present. 2. Among cefaclor (CCL), cephalexin, lomefloxacin, latamoxef and flomoxef (FMOX), FMOX was, in general, superior to the other drugs in terms of antibacterial activities against those strains isolated from semen. 3. Bacterial changes were observed in the semen specimens from 11 subjects who were subjected to oral administration of CCL (1,500 mg/days). After the treatment, 25 strains of bacteria disappeared but 7 strains remained among 32 strains that were present before treatment, and 23 strains appeared due to superinfection. PMID- 2112206 TI - [Susceptibility of bacteria isolated from patients with lower respiratory tract infections to antibiotics (1987)]. AB - Since 1981, in cooperation with research institutions across the nation, Ikemoto, et al. have been collecting clinical isolates from patients with respiratory tract infections and conducting an annual retrospective survey of patients' background factors and of isolated strains and their sensitivities to various antibacterial agents and antibiotics. In the period from October, 1987 to September, 1988, 17 institutions participated in the survey and a total of 706 strains which were demonstrated to be causative organisms were isolated from 562 patients with respiratory tract infections. Strains were mostly isolated from the sputum. The taxonomic breakdown of these strains was: Staphylococcus aureus (69 strains), Streptococcus pneumoniae (120), Haemophilus influenzae (170), Mucoid producing Pseudomonas aeruginosa (42), Non-mucoid-producing P. aeruginosa (87), Escherichia coli (11), Klebsiella pneumoniae (35), Brahamella catarrharis (72), etc. Of these strains, 629 were used to determine MICs of various antibacterial agents and antibiotics for susceptibility analyses. Relationships between patient backgrounds and diagnoses and between infections diseases and causative organisms were also investigated. Most of the major causative organisms, such as H. influenzae and P. aeruginosa, showed no substantial changes from previous years, with regard to their sensitivities to antibiotic agent, but S. aureus, particularly methicillin/cephem-resistant strains of S. aureus (MCRSA) showed somewhat lower sensitivity to beta-lactams, and as in recent years, to ofloxacin, a new quinolone drug, as well. Regarding background factors of patients, the age distribution was heavily concentrated in age brackets of 50 years and older, thus patients in these age group accounted for 75.2% of all the patients, which was comparable to 73.5% in 1985 and 77.9% in 1986. Among infections encountered, bacterial pneumonia was most frequent at 28.3%, followed by chronic bronchitis (27.2%) and bronchiectasis (16.0%). Bacterial pneumonia was actually the most frequent, throughout the entire age groups accounting for 34.3% of patients up to 29 years, 26.6% in the group of 30-69 years and 30.7% in patients aged 70 years and older. Chronic bronchitis was next most frequent and accounted for 20.0%, 26.4% and 30.7% among the three age groups, respectively. Breaking down clinical isolates by diagnosis, H. influenzae, S. pneumoniae and P. aeruginosa were isolated frequently from most of the infectious diseases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2112207 TI - [Clinical evaluation of therapy for aspiration pneumonia with imipenem/cilastatin sodium]. AB - In an open, prospective, multicenter trial the clinical efficacy of imipenem/cilastatin sodium (IPM/CS) for the treatment of 14 cases with aspiration pneumonia was investigated. The mean age was 75.4 years old. Diseases of central nervous system were present in 11 cases, cardiovascular diseases, pulmonary diseases and diabetes mellitus in 2 cases each respectively. Seven cases were community-acquired and another seven were hospital-acquired. Six cases were moderate and 8 cases were severe. Causative organisms were determined in 9 cases (64.3%), multiple causative organisms were isolated in 3 cases. Isolated organisms were Staphylococcus aureus (4), Pseudomonas aeruginosa (3), Klebsiella pneumoniae (3), Escherichia coli (1), Acinetobacter calcoaceticus (1). Detection of anaerobes was not attempted. Clinical effects of IPM/CS were excellent in 3, good in 8, fair in 2, poor in 1, the efficacy rate was thus 78.6%. P. aeruginosa was isolated from 2 out of 3 cases in which therapy with IPM/CS failed. Monotherapy with IPM/CS appears to be highly effective for cases of aspiration pneumonia, but the disease due to IPM-resistant P. aeruginosa is an exception. PMID- 2112208 TI - [Clinical efficacy of imipenem/cilastatin sodium in patients with respiratory tract infections caused by Pseudomonas aeruginosa]. AB - The clinical utility of imipenem/cilastatin sodium (IPM/CS, Tienam) was studied in 9 patients with respiratory tract infections from whom Pseudomonas aeruginosa was isolated using transtracheal aspiration. The patients treated were 6 males and 3 females, with ages between 42 and 78 years. The infections diagnosed were chronic bronchitis in 5 patients, diffuse panbronchiolitis in 2 and bronchopneumonia in 2. P. aeruginosa alone was isolated from 6 patients and concomitantly with other organisms from 3. Clinical efficacy was good in 6 patients, fairly good in 1 and poor in 2. No side effects or abnormal laboratory test values were observed, except for a slight elevation of LDH in 1 patient. From these results, it appears that IPM/CS is a clinically useful antibiotic for the treatment of respiratory tract infections caused by P. aeruginosa. PMID- 2112209 TI - [Inflammatory reaction and laboratory tests: serum amyloid A (SAA) protein]. AB - Serum amyloid A protein (SAA) is a sensitive acute phase reactant. Here, the assay of SAA in serum and its clinical significance are reviewed. SAA was measured simply by radial immunodiffusion and enzyme immunoassay with rabbit anti amyloid A antibodies, however further investigation is necessary because SAA is an insoluble apolipoprotein. The concentration of SAA was 1.5-3.0 folds higher at physiological states, and 3.0-10.0 folds higher at inflammatory states than that of C-reactive protein (CRP). Therefore, SAA might be a sensitive and useful method for full observation of diseases. At the acute phase such as myocardial infarction, SAA changed at the same time as CRP. Most inflammatory disorders, for example, rheumatoid arthritis and malignant tumors which show elevation of CRP, showed elevation of SAA. These two proteins were strongly correlated, but showed no disease specificity. Also at secondary amyloidosis which was caused by deposition of SAA fragments, the level of SAA did not indicate the presence of amyloid. Only at the time of kidney allograft rejection for a recipient, was SAA elevated markedly in comparison with CRP. Recently, we developed a method of quantitative analysis of SAA isotypes and applied it in a few cases. Although significant features for diseases have not been obtained yet, such analysis might become useful for the physiological and pathological understanding of SAA. PMID- 2112210 TI - Serotypes and antimicrobial susceptibility of Pseudomonas aeruginosa strains isolated from diseased dogs. AB - Strains of Pseudomonas aeruginosa isolated from diseased dogs in Tokyo area during 1983 through 1986 were serotyped and assayed for antimicrobial susceptibility to obtain an epizootiological aspect of canine P. aeruginosa infection. Major sources of specimens were ear and nasal discharges and urine. The results of O-antigen typing using a monoclonal antibody kit showed that the most predominant serotype was type M. Types G and B were also major serotypes. In a yearly distribution of serotypes, type I was almost limited in 1986, and was isolated mainly from surgical wounds, which showed an episode of nosocomial infection, whereas that of type M or B was dispersed during 4 years from 1983 to 1986. As a result of antimicrobial susceptibility test, most canine strains were considered to be susceptible to 4 drugs, which were commonly used in both human and veterinary clinics, in contrast to human isolates. PMID- 2112211 TI - Experimental studies of the load reducing effects of nitroglycerin in heart failure. AB - The load-reducing effect of nitroglycerin (NTG), a vasodilator, was studied in dogs with heart failure. The chordae tendineae of the mitral valve were transected to induce acute mitral regurgitation (MR) for hemodynamic evaluation. By such surgical treatment, preload indices such as left ventricular end diastolic pressure (LVEDP) and left atrial pressure (LAP) increased significantly, and subsequent cardiac dysfunction and heart failure were indicated by another decrease in stroke volume, myocardial contractility, forward flow, and myocardial oxygen consumption. To dogs with artificially established acute MR, 3 micrograms/kg/min of NTG was administered intra-arterially by means of a continuous infusion, that resulted in decrease of LVEDP, LAP and central venous pressure (CVP). Thus, a reduction of preload was determined. Simultaneously, afterload indices such as aortic systolic pressure (Aos), aortic mean pressure (Aom) and total peripheral resistance (TPR) decreased remarkably. Afterload reduction depended on the amount of venous return; therefore, an extra corporeal circulation system was applied in order to supply a constant venous return before NTG administration. This caused a significant decrease in aortic diastolic pressure (Aod), Aos, Aom, left ventricular systolic pressure (LVSP) and TPR, and an increase in myocardial contractility and cardiac output. This suggested that afterload reduction might be realized by the vasodilatory effect of NTG on the resistance vessels. PMID- 2112212 TI - Origin of abomasum gas in the cows with displaced abomasum. AB - The gas composition of the rumen and the abomasum were investigated in 71 cows including 25 cows with displaced abomasum. The ratio of methane (CH4) to CO2 in the abomasum gas was higher than that in the rumen. In the incubated mixtures of fresh rumen fluid, CH4 was detected at a high concentration, while a small amount of CO2 and CH4 was found in incubated mixtures of fresh abomasum fluids. Hence, it was suggested that the gas in the abomasum originated not from the abomasum itself but from the rumen. In cows fed with mixed roughages and concentrates, the rumen CO2:CH4 ratio was higher compared with cows fed with roughages alone. Marked changes in rumen gas composition were presumed to be associated with changes in abomasum gas composition. Consequently, it is possible that feeding a large quantity of concentrates may increase the flow rate of the ingesta through the forestomach, so that the return rate of gas separated from the ingesta in the abomasum to the forestomach may also increase. Therefore, the frequent accumulation of a large amount of gas with concomitant changes in the total volatile fatty acid (VFA) concentration in the abomasum caused abomasal atony and subsequently displaced abomasum. PMID- 2112213 TI - Effects of cyclosporin A on susceptibility and interferon-generating capacity in mice infected with Toxoplasma gondii. AB - Cyclosporin A (Cs-A), a potent immunosuppressant, was administered to mice to evaluate the role of T lymphocytes for the development of a protective immunity to an obligate intracellular protozoan parasite, Toxoplasma gondii. Although daily administration of various amounts of Cs-A for 7 days enhanced the host susceptibility at all doses employed, a dose-dependent manner of Cs-A treatment was not observed as far as the dosage regimens applied here are concerned; mice died at the same rate (40%) among the groups receiving various amounts of Cs-A. Cs-A treatment had a differential effect on the course of disease depending on how it was given in relation to infection. All mice receiving 50 mg of Cs-A per kg per day for 10 days from the beginning of infection eventually died of toxoplasmosis. Cs-A did not suppress the production of intereferon(IFN) alpha/beta that was induced shortly after the infection, whereas it reduced greatly the ability of Toxoplasma-infected mice to produce IFN-gamma induced by stimulation with Toxoplasma lysate antigen (TLA). Moreover, the decrease in IFN gamma production correlated with an increase in the parasitic growth in the peritoneal cavities of Cs-A-treated mice. These results suggest that the immunosuppressive effect of Cs-A on the primary Toxoplasma infection in mice is expressed by inhibiting the development of effector T cells responsible for the production of IFN-gamma. PMID- 2112214 TI - 19th annual UCLA symposium: Signal transduction by G proteins. Abstracts. PMID- 2112215 TI - New initiatives in health services research: can the pieces of the health-care puzzle be put together? PMID- 2112216 TI - Potential effectiveness of quality assurance screening using large but imperfect databases. AB - To examine the effect of imprecise classification of patient risk (severity of illness) on an otherwise highly accurate quality assurance screening technique, data on clinical outcomes were generated for a simulated hospital system consisting of 108 facilities treating approximately 565,000 patients a year. In these simulations, marked differences in facility size, casemix distribution, and quality of care were combined with random variations in outcome. Pooled data for all 108 facilities were used to create algorithms that combined 468 discrete patient risk classifications into either ten or three groups with broad, overlapping ranges of patient-specific risks of unfavorable clinical results. When derived algorithms were applied to independently generated facility-specific data, the ability to identify hospital systems with and without quality of care problems was maintained with ten, but not with three, risk groups. However, even three moderately heterogeneous risk groups were sufficient to preserve a high degree of sensitivity and specificity in screening for potential quality of care problems within individual facilities. Thus, outcome-based quality assurance screening can be highly accurate in actual health care situations in which only imprecise estimations of patient-specific risk can be achieved. PMID- 2112217 TI - Targeting assessments of magnetic resonance imaging in suspected multiple sclerosis. AB - Decision-analytic methods can be valuable for targeting research in technology assessment. They can indicate whether further evaluation of a technology is warranted, and if so, which variables are key determinants of its clinical utility and cost-effectiveness. This approach was tested on a salient issue- whether magnetic resonance imaging (MR) should be used in evaluating patients with mild neurologic symptoms who might have multiple sclerosis (MS). The authors developed a decision-analytic model to assess the expected utility and costs associated with immediately using MR in this situation, compared with waiting for further symptoms to emerge before testing. Sensitivity analyses demonstrated that priorities for technology assessment research include estimating the value of information to patients in resolving uncertainty, evaluating the impact on patients of being labeled with a diagnosis of MS, and measuring the test characteristics of MR. PMID- 2112218 TI - Reducing sick leave costs by shortening waiting periods for elective surgery. AB - Some sick leave of patients waiting for elective surgery could be avoided if these patients were treated with less delay. One way of achieving this is to give priority to patients on sick leave. Problems of fairness that such a policy would raise might be solved by assuring that part of the production gains stemming from avoided sick leave were used to increase treatment capacity to benefit all patients, including those not on sick leave. Another way to reduce sick leave due to waiting time is to increase supply temporarily and reduce treatment backlog without changing priorities among patient groups. If treatment thresholds are unaffected, such a temporary increase in supply will relieve all later patients of some of their waiting and render a production gain that may exceed marginal costs. If treatment thresholds are lowered as a result of waiting time's being reduced, there will still be production gains in patients benefiting by the temporary increase in supply, but in this situation the gains may cover only part of marginal costs. PMID- 2112219 TI - Physicians' accuracy in manual computation. AB - Parenteral alimentation fluids are now part of routine nutritional support in the neonatal intensive care unit, and a number of software products are available to help physicians with the formulations. Use of these products is based on the assumption that an appreciable amount of error occurs during manual computation, but few attempts to measure this error have been reported. I performed a retrospective analysis of the accuracy of physicians' calculations of the formulas for parenteral alimentation fluid. In addition, I assessed the ability of our institution's computer-based parenteral alimentation program to correct the deficiencies identified. The study showed no significant differences between physicians' calculations as a whole and their paired ideal values. Individual errors did occur, however, and were large enough to have potential clinical importance. Use of the parenteral alimentation program was found to correct these errors. PMID- 2112220 TI - The role of IFN-gamma in murine Salmonella typhimurium infection. AB - Influence of both recombinant interferon gamma (r-IFN-gamma) and monoclonal anti IFN-gamma on murine Salmonella typhimurium infection was studied in vivo. As a challenge we used either a virulent or an avirulent strain of S. typhimurium. The avirulent strain is unable to replicate in the mouse spleen. The effect of IFN gamma or anti-IFN-gamma treatment on infection was assayed by counting the number of bacteria in the spleens 1, 2, 4 or 7 days after infection. Exogenously supplied IFN-gamma was found to decrease the number of both the virulent and the avirulent bacteria in the spleens 1 day after challenge but thereafter had no detectable effect. Anti-IFN-gamma-treated mice were unable to clear a sub-lethal dose of the virulent bacteria. The enhanced growth of the bacteria in the spleen was seen after 2 days of infection. In the spleens of anti-IFN-gamma-treated mice and control mice the fate of the non-replicating bacteria was similar. We conclude that the mice produce IFN-gamma during the early phase of Salmonella infection and that this causes a reduction in the apparent growth rate of the virulent bacteria. Because the avirulent bacteria, which do not multiply, were not affected by anti-IFN-gamma treatment, the effect of IFN-gamma is primarily bacteriostatic rather than bactericidal. After challenge, the production of IFN gamma seems to start with a lag of approximately 2 days. PMID- 2112221 TI - Atherosclerosis: the importance of HDL cholesterol and prostacyclin: a role for niacin therapy. AB - Niacin reduces the incidence of non-fatal myocardial way infarction, confers a significant long-term survival benefit after recovery from myocardial infarction, and has had many years of study and usage by the medical community. Recent evidence suggests that via mechanisms which elevate HDL cholesterol and also release endogenous prostacyclin, niacin should be a potent agent in the long-term treatment of atherosclerosis. PMID- 2112222 TI - An hypothesis for treating factor VIII inhibitors with different heat treated products. PMID- 2112223 TI - Screening of blood donations for hepatitis C virus antibody. PMID- 2112224 TI - [Inhibition of translation of immunoglobulin mRNA in vitro using an alkylating oligonucleotide derivative]. AB - Effect of complementary oligonucleotides and their reactive derivatives on translation of mouse immunoglobulin G kappa light chain was investigated. It was found that oligonucleotide pTGCTCTGGTTT and shorter oligonucleotides complementary to the coding sequence of the mRNA (nucleotides 205-215) do not arrest translation of the mRNA in the rabbit reticulocyte cell-free translation system. Preincubation of the mRNA with the alkylating 4-(N-2-chloroethyl-N methylamino)benzyl-5'-phosphamide derivative of the oligonucleotide completely suppresses the synthesis of the protein thus demonstrating higher efficiency of the reactive oligonucleotide derivatives as inhibitors of the mRNA function. PMID- 2112225 TI - [Unusual structure of the regulatory region of the riboflavin biosynthesis operon in Bacillus subtilis]. AB - In vitro mutagenesis with methylhydroxylamine and nitrosomethylurea was used to obtain a number of Bacillus subtilis mutants impaired in flavin-dependent response. Mutants displayed varying degree of flavin-dependent repression of riboflavin synthase and of 6,7-dimethyl-8-ribityl-lumasine accumulation. Single nucleotide substitutions were detected by DNA sequencing in all of the mutants, affecting the 48 b.p. target area between the mRNA start and the AUG of the first gene. PMID- 2112226 TI - Developmental expression of a Theileria annulata merozoite surface antigen. AB - Culture of a lymphoblastoid cell line infected with the macroschizont stage of the protozoan parasite Theileria annulata at 41 degrees C induces differentiation to the next stage, the merozoite. We have demonstrated that this development results in the loss of monoclonal antibody epitopes associated with the macroschizont stage, and the appearance of epitopes associated with the piroplasm (the intra-erythrocytic stages). One of the monoclonals (5E1) was shown by immunoelectron microscopy to bind to the surface of heat-induced culture forms which had size and structural characteristics of the merozoite. The monoclonal was found to detect two polypeptides of 30 kDa and 25 kDa in extracts of piroplasms. The 30-kDa polypeptide was also detected in a merozoite extract, but was not detected in an extract derived from macroschizont-infected lymphoblastoid cells. We conclude that the heat-induced differentiation of T. annulata in vitro results in the expression of a 30-kDa molecule which is located at the surface of the merozoite, and discuss the potential of this molecule as a component in a subunit vaccine. PMID- 2112227 TI - The role of Veterans Affairs hospitals in the health care system. PMID- 2112228 TI - Potassium channels. Mixing and matching. PMID- 2112229 TI - Evidence for the formation of heteromultimeric potassium channels in Xenopus oocytes. AB - Potassium channels show a wide range of functional diversity. Nerve cells typically express a number of K+ channels that differ in their kinetics, single channel conductance, pharmacology, and sensitivity to voltage and second messengers. The cloning of the Shaker gene in Drosophila, and of related genes, has revealed that the encoded K+ channel polypeptides resemble one of the four internally homologous domains of the alpha-subunits of Na+ channels and Ca2+ channels, indicating that K+ channels may form by the co-assembly of several polypeptides. In this report we provide evidence that the Shaker A-type K+ channels expressed in Xenopus oocytes contain several Shaker polypeptides, that heteromultimeric channels may form through assembly of different channel polypeptides, that the kinetics or pharmacology of some heteromultimeric channels differ from those of homomultimeric channels, and that channel polypeptides from the fruit fly can co-assemble with homologous polypeptides from the rat. We suggest that heteromultimer formation may increase K+ channel diversity beyond even the level expected from the large number of K+ channel genes and alternative splicing products. PMID- 2112230 TI - Small GTP-binding protein associated with Golgi cisternae. AB - Eukaryotic cells seem to use GTP hydrolysis to regulate vesicular traffic in exocytosis and endocytosis. The best evidence for this comes from studies on the yeast Saccharomyces cerevisiae that have identified two small Ras-related GTP binding proteins, Sec4p and Ypt1p, which control distinct stages of the secretory pathway. In mammalian cells the effects of a non-hydrolysable GTP analogue, GTP gamma S, on different transport events have suggested that they also have proteins functionally related to yeast Sec4p and Ypt1p. The rab genes have recently been cloned and sequenced for rat and human and their proteins have highly conserved domains in common with Sec4p and Ypt1p (including a putative effector binding site). They are therefore good candidates for GTP-binding proteins involved in intracellular transport in mammalian cells. One of the Rab proteins (Rab1p) is the mammalian counterpart of Ypt1p (ref. 13). Here we report the localization of the protein Rab6p to the Golgi apparatus in several cell types. By immunolabelling and electron microscopy, Rab6p appears to be concentrated predominantly on the medial and trans cisternae and distributed over their entire surface. PMID- 2112232 TI - Structure of the fibronectin type 1 module. AB - The rapid accumulation of sequence data has provided insight into the evolution of proteins and led to the identification of 'mosaic proteins'. These proteins have evolved by duplication, insertion and deletion of a common pool of structural units or modules, yet their biological functions are diverse. They are involved in cell adhesion and migration, embryogenesis and the pathways of blood clotting, fibrinolysis and complement. The modular units are defined by 'consensus sequences' which often include conserved disulphide bonds. Despite the available sequence information, little is known of the tertiary structure of mosaic proteins. If, however, the 'consensus structure' of the modules were known, valuable structural information could be inferred about a wide variety of proteins and biological systems. An important mosaic protein is fibronectin, an extracellular matrix protein that consists of three types of module (see refs 3, 7 for reviews). Here we describe the structure of the fibronectin type 1 module which appears twelve times in fibronectin and is also found in factor XII and tissue plasminogen activator. The module was produced using a yeast expression system and the structure was determined in solution using 1H NMR. This methodology promises to be extremely powerful in the investigation of modules from a wide range of mosaic proteins. PMID- 2112231 TI - The LDL receptor pathway delivers arachidonic acid for eicosanoid formation in cells stimulated by platelet-derived growth factor. AB - Animal cells can convert 20-carbon polyunsaturated fatty acids into prostaglandins (PGs) and leukotrienes. These locally produced mediators of inflammatory and immunological reactions act in an autocrine or paracrine fashion. Arachidonic acid (AA), the precursor of most PGs and leukotrienes, is present in the form of lipid esters within plasma lipoproteins and cannot be synthesised de novo by animal cells. Therefore, AA or its plant-derived precursor, linoleic acid, must be provided to cells if PGs or leukotrienes are to be formed. Because several classes of lipoproteins, including low-density lipoproteins (LDL), very-low-density lipoproteins, and chylomicron remnants, are taken up by means of the LDL receptor, and because LDL and very-low-density lipoproteins, but not high-density lipoproteins, stimulate PG synthesis, we have suggested previously that PG formation is directly linked to the LDL pathway. Using fibroblasts with the receptor-negative phenotype of familial hypercholesterolaemia and anti-LDL receptor antibodies, we show here that LDL deliver AA for PG production and that an LDL receptor-dependent feedback mechanism inhibits the activity of PGH synthase, the rate-limiting enzyme of PG synthesis. These results indicate that the LDL pathway has a regulatory role in PG synthesis, in addition to its well-known role in the maintenance of cellular cholesterol homeostasis. PMID- 2112233 TI - [GISSI-2; the beginning of the end or the end of the beginning for tissue plasminogen activator in acute myocardial infarct?]. PMID- 2112234 TI - [Revised definition of the concept rhesus-negative blood donor; practical experiences]. AB - In 1987 the Central Medical Blood-transfusion Committee of the Netherlands Red Cross decided to modify their definition of 'Rh-negative' as it applied to blood donors. Until then the term Rh-negative had been reserved for donations that grouped as C- and E-negative and failed to react with IgG anti-D by the indirect antiglobulin test (IAT). From June 1987, however, donations were considered to be Rh-negative if they failed to react with two strong anti-D sera. An evaluation is presented over the first one and a half years of working with the new definition, the problems that were encountered and the measures that are taken to guarantee the quality of Rh testing. PMID- 2112235 TI - Annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. San Diego, California, September 9-13, 1990. 1990 Instruction Course Program. PMID- 2112236 TI - Basic immunologic principles underlying vaccination procedures. AB - Mass immunization programs and routine immunization of infants and children have significantly reduced the incidence of several serious diseases. This article describes the immunologic principles that guide the use of vaccines and explains the mechanisms of protective immunity, adverse side reactions associated with immunization, and new molecular approaches for producing vaccines. PMID- 2112237 TI - Clinical observations of children with pleuropneumonia due to Mycoplasma pneumoniae. AB - A comparative study on the clinical presentation of Mycoplasma pneumoniae infection was performed in 56 patients with pleuropneumonia and those who had pneumonia without pleural effusion. The latter consisted of 773 cases; their age distribution reached a peak at 3-5 years of age in males and at 4-6 years in females. The 56 cases with pleuropneumonia were distributed among children of all ages. Pneumococcal infection was demonstrated by blood culture in one of 56 cases. Serological tests revealed a higher prevalence of mixed viral infections among children with pleuropneumonia (18/44) than with pneumonia but no effusion (69/419). There was a tendency toward a severe and prolonged course of illness with strong indications of infection among pleuropneumonia cases. Complications such as exanthema or liver dysfunction were observed more frequently among pleuropneumonia cases than among simple pneumonia cases. These results suggest that other pathogenic agents or unknown host reactions to these agents may modify the clinical picture of pleuropneumonia caused by M. pneumoniae. PMID- 2112238 TI - On Branhamella catarrhalis pneumonia. PMID- 2112239 TI - Erythroid cultures and erythropoietin assay. Clinical and diagnostic value. AB - In vitro cultures of erythroid progenitors and radioimmunoassay of erythropoietin (Epo) are 2 recently available techniques. It is possible to assess their relevance in various hematological disorders. Erythroid cultures can be performed in the investigation of polycythemias, pure red cell aplasias (PRCA) and refractory anemias. In primary polycythemias "spontaneous" colonies appear in vitro whereas this phenomenon is never observed in secondary polycythemias. These so called "spontaneous" colonies have been demonstrated with a lower incidence in all myeloproliferative disorders. Therefore, if the absence of spontaneous colonies does not permit us to eliminate the presence of a myeloproliferative syndrome aside from polycythemia vera, their presence does seem pathognomonic of a myeloproliferative disorder. In acquired chronic pure red cell aplasia in adults, a strong correlation is found between the in vitro growth of erythroid colonies and the results of immuno-suppressive treatment. In refractory anemias erythroid cultures do not have either diagnostic, or prognostic interest. Serum epo level does not have a high discriminatory value in distinguishing between primary and secondary erythrocytosis. Indeed in PV, the Epo level is generally low or normal, in secondary polycythemias Epo level is high or normal. There is an important overlap between the two groups. Epo level determination can have a therapeutic incidence. Administration of recombinant Epo seems justified only in patients both sufficiently anemic to warrant transfusions and in whom Epo level is low in comparison with the degree of anemia. PMID- 2112241 TI - Regulation of kappa immunoglobulin gene transcription in vitro. AB - An in vitro transcription system has been established with a whole-cell extract from the human Burkitt's lymphoma, Daudi, cell line. The B cell extract has been compared with a HeLa cell extract in an effort to study lymphocyte-specific regulatory factors of kappa light chain gene transcription. Both extracts were capable of transcribing Vk genes and other RNA polymerase II dependent genes. Alpha-amanitin at [0.1 micrograms/ml] completely inhibited the accumulation of transcripts in both systems. At low DNA template concentrations the kappa intronic enhancer stimulated Vk promoter transcription 3-7 fold in B cell extracts. The enhancer-dependent transcription was abolished by excising the enhancer from the test plasmid with Eco R1. Both Vk promoter and enhancer dependent transcription in HeLa extracts was undetectable at low [DNA]. These results demonstrate that kappa enhancer stimulation of Vk transcription in vitro is observed in B cell extracts only under conditions of low DNA template concentration. PMID- 2112240 TI - A conjugation-specific gene (cnjC) from Tetrahymena encodes a protein homologous to yeast RNA polymerase subunits (RPB3, RPC40) and similar to a portion of the prokaryotic RNA polymerase alpha subunit (rpoA). AB - The cnjC gene from the protozoan Tetrahymena thermophila was completely sequenced. The deduced gene product was found to have significant sequence similarity to the yeast and prokaryotic RNA polymerase subunits involved with subunit assembly. Since cnjC is active only during the sexual stage (conjugation) of Tetrahymena's life cycle, these results indicate it may be part of a novel type of transcriptional control. The yeast proteins to which the Tetrahymena cnjC is homologous are the 40 kd protein of RNA polymerases I and III (coded for by gene RPC40) and the third-largest subunit of RNA polymerase II (coded for by gene RPB3). The degree of similarity of the cnjC protein to the two yeast subunits was found to be greater than the similarity of the two yeast subunits to each other. The alpha subunit of the core RNA polymerase from prokaryotes (coded for by gene rpoA) was found to have regions of similarity to the cnjC protein as well as to the subunits encoded by RPC40 and RPB3. Regions of high conservation among the four proteins are noted. The significance of these results is discussed. PMID- 2112242 TI - Isolation of human cDNA clones of jun-related genes, jun-B and jun-D. PMID- 2112243 TI - Second-line antirheumatic drugs in the elderly with rheumatoid arthritis: a post hoc analysis of three controlled trials. AB - This study assessed the relative efficacy and toxicity of second-line antirheumatic drugs in patients 65 years of age or older compared to younger counterparts. The results of three prospective, double-blind, parallel, randomized, multicenter trials were reanalyzed, stratifying outcomes by intervention and patient age. Efficacy was assessed by categorizing patient responses as follows: important improvement, no meaningful change, or progressive disease. Toxicity was analyzed by comparing withdrawal rates due to adverse effects. The three trials compared the following treatments: (1) D-penicillamine 10-12 mg/day versus azathioprine 1.25-1.5 mg/kg/day; (2) gold sodium thiomalate 50 mg intramuscularly weekly versus auranofin 6 mg/day versus placebo; and (3) pulse oral methotrexate 7.5-15.0 mg weekly versus placebo. At baseline, 103 patients age 65 or older were similar to 485 patients less than 65 years of age, with the exception of disease duration in all studies and erythrocyte sedimentation rate in one study. For patients completing each study, efficacy outcomes based on age were not significantly different. Withdrawal rates due to adverse drug reactions were also not significantly different. PMID- 2112244 TI - Acute polymyositis in an adult associated with Mycoplasma pneumoniae infection. PMID- 2112245 TI - Long term treatment of myasthenia gravis with azathioprine. AB - Twenty-seven patients with myasthenia gravis have been treated with azathioprine in conjunction with pyridostigmine and prednisolone for a total of 138 patient years. Side effects necessitated discontinuation of treatment in only four patients. Treatment with azathioprine was associated with marked clinical improvement in all the remaining 23 patients, resulting in reduction in the dose of pyridostigmine and prednisolone. The number of hospital admissions as well as the number of episodes of respiratory failure were markedly reduced. PMID- 2112246 TI - [Dynamics of accumulation of extracellular lipoteichoic acid in Bacillus cereus]. AB - The dynamic of accumulation of extracellular lipoteichoic acid (LTA) was studied depending on the growth stage of Bacillus cereus st. 96. A maximum amount of extracellular LTA was detected in the middle of the exponential growth. The quantity of the biopolymer present in the culture medium at the beginning of the stationary growth under conditions of catabolite repression of sporulation and without repression was found to be different. Experimentally increased concentrations of LTA inhibited B. cereus sporulation. Besides, dormant spores of B. cereus st. 96 were found to contain LTA. PMID- 2112247 TI - [Conditions of the L-lysine decarboxylase biosynthesis in a culture of Vibrio sp]. AB - The effect of L-lysine HCl concentrations, pH, temperature and cultivation conditions on the synthesis of intracellular lysine decarboxylase (LDC) by Vibrio sp. was studied. The highest LDC activity was observed in a 4-hour culture grown at 30 degrees on a nutrient medium, pH 5.15 containing 0.9% L-lysine HCl as an inducer. Under these conditions the LDC activity of the bacterium was 8.43 U/mg dry cells. PMID- 2112248 TI - Free energy changes associated with amino acid substitution in proteins. AB - The estimation of free energy differences from computer simulation of macromolecular systems is important for rational strategies for drug design and for protein engineering. As an example of one mutation, we have studied the free energy change resulting from the conversion of a polar group (OH) to an apolar group (CH3) in aqueous solution. We have estimated the effect of various local environments on the magnitude of the free energy difference and find that significant environmental effects are found. We have also studied the reliability of the results in detail. PMID- 2112249 TI - Phospholipid in the hexagonal II phase is immunogenic: evidence for immunorecognition of nonbilayer lipid phases in vivo. AB - Immunization of mice with phosphatidylethanolamine in the hexagonal II phase but not the bilayer phase resulted in the induction of anti-phospholipid antibodies. These antibodies, which were strongly reactive with phosphatidylethanolamine and crossreactive with cardiolipin, had functional lupus anticoagulant activity and were characteristic of autoantibodies common in patients with autoimmune disease. Recognition of the hexagonal II phase by the afferent limb of the immune system suggests that nonbilayer phospholipids can arise in the course of membrane remodeling and induce the autoantibodies of disease. PMID- 2112250 TI - Overexpression of Cu-Zn superoxide dismutase in Drosophila does not affect life span. AB - Aging and disease processes may be due to deleterious and irreversible changes produced by free radical reactions. The enzyme copper-zinc superoxide dismutase (Cu-Zn SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) performs a protective function by scavenging superoxide radicals. The Cu-Zn SOD gene (Sod) cloned from Drosophila melanogaster was introduced via P element-mediated transformation into the germ line. Homozygous lines carrying additional copies of the Sod gene were recovered and characterized. Increases in Sod transcripts and enzyme activity were observed in the transformed lines, indicating that all of the sequence information required for gene expression is contained on the inserted gene fragment. The effects of additional SOD on oxygen free radical metabolism and longevity were investigated. Additional SOD did not markedly affect oxygen metabolism or longevity. PMID- 2112251 TI - Genetic analysis of the Kirsten-ras-revertant 1 gene: potentiation of its tumor suppressor activity by specific point mutations. AB - Kirsten-ras-revertant 1 (Krev-1) cDNA encodes a ras-related protein and exhibits an activity of inducing flat revertants at certain frequencies (2-5% of total transfectants) when introduced into a v-K-ras-transformed mouse NIH 3T3 cell line, DT. Toward understanding the mechanism of action of Krev-1 protein, we constructed a series of point mutants of Krev-1 cDNA and tested their biological activities in DT cells and HT1080 human fibrosarcoma cells harboring the activated N-ras gene. Substitutions of the amino acid residues in the putative guanine nucleotide-binding regions (Asp17 and Asn116), in the putative effector binding domain (residue 38), at the putative acylation site (Cys181), and at the unique Thr61 all decreased the transformation suppressor activity. On the other hand, substitutions such as Gly12 to Val12 and Gln63 to Glu63 were found to significantly increase the transformation suppressor/tumor suppressor activity of Krev-1. These findings are consistent with the idea that Krev-1 protein is regulated like many other G proteins by the guanine triphosphate/guanine diphosphate-exchange mechanism probably in response to certain negative growth regulatory signals. PMID- 2112252 TI - cDNA cloning, sequence, and expression of carbonic anhydrase in Chlamydomonas reinhardtii: regulation by environmental CO2 concentration. AB - cDNA clones for the periplasmic carbonic anhydrase (CA; carbonate hydro-lyase, EC 4.2.1.1) of Chlamydomonas reinhardtii cells were isolated and characterized. The fact that the cloned cDNA fragments encoded a 377-amino acid polypeptide (41,626 Da) consisting of an NH2-terminal hydrophobic signal peptide of 20 amino acids, a large (35,603 Da) subunit polypeptide, and a small (4144 Da) subunit polypeptide indicates that the two subunits are cotranslated as a precursor polypeptide. The amino acid sequence of mature subunits deduced from the nucleotide sequence showed 20-22% homology with human CA isozymes (CAI, CAII, and CAIII). Three zinc liganded histidine residues and those forming a hydrogen-bond network to zinc bound solvent molecules were highly conserved in the plant and animal enzymes. Three possible asparagine-linked glycosylation sites were found in the large subunit. Northern blot analysis was carried out using the cDNA fragment as a probe. The level of 2.0-kilobase CA mRNA increased within 1 hr when CO2 concentration of the bubbling gas was changed from 5% to 0.04% (air level) in the presence of light. On the other hand, CA mRNA did not accumulate when CO2 concentration was lowered in the dark. Experiments using 3-(3,4-dichlorophenyl) 1,1-dimethylurea showed that photosynthesis is absolutely required for the accumulation of CA mRNA. These results indicate that CA biosynthesis is regulated by changes in environmental CO2 concentration as well as light at the level of mRNA abundance. PMID- 2112253 TI - Genetic differences in follicular DNA synthesis between two strains of hamsters. AB - This study was designed to compare our previous results on ovarian follicular DNA synthesis by hamsters obtained from Sasco Laboratories with a different breeding colony: Harlan. Follicles from proestrous Harlan hamsters required twice as much [3H] thymidine and a minimum of 4 hr of in vitro exposure to 100 ng of ovine follicle-stimulating hormone (FSH) before a significant increase in DNA synthesis was elicited compared with 30-120 min for the Sasco breed. Peak responsiveness to FSH was observed at 8-hr incubation for the Harlan strain with significant increases in DNA per follicle at 8-12 hr. Both strains increased DNA synthesis with as little as 25 ng of ovine FSH and the response was elicited in all growing follicles, from preantral stages with one to four layers of granulosa cells, lacking theca (Stages 1-4) to mature antral follicles (Stages 8-10). A recombinant bovine FSH, devoid of luteinizing hormone activity, was not as effective as ovine FSH (which has 4% luteinizing hormone contamination) in stimulating DNA synthesis by large preantral and antral follicles. In vitro responsiveness to ovine FSH was abolished in the absence of Ca2+ in the culture medium and 0.05 mM Ca2+ was the optimal amount. For both strains of hamsters, the highest rate of DNA synthesis in response to endogenous gonadotropins was on the morning of estrus--when the second surge of FSH was in progress--and Harlan follicles in vitro also showed maximal stimulation by FSH on this day. Where the two strains differed was that the Harlan strain did not show an increase in follicular DNA synthesis on the afternoon of proestrus--when the preovulatory increase in gonadotropins commenced. When expressed as DNA per follicle, DNA approximately doubled from Stages 1 to 5 and then entered a new growth phase at Stage 6 (large preantral follicles) with a steeper increase. Collectively, these experiments show that strain characteristics can alter the latency and degree of follicular DNA replication in response to endogenous or exogenous FSH. PMID- 2112254 TI - Expression of beta-galactosidase in preimplantation ovine and porcine embryos. AB - Knowledge regarding the timing of embryonic expression of the mammalian genome is of relevance for the development of preimplantation diagnostic methods for human genetic diseases. For development of preimplantation diagnosis of lysosomal storage diseases, it will be necessary to know at which embryonic stage the genes for lysosomal enzymes are expressed. In previous studies by other investigators, it has been shown that lysosomal alpha- and beta-galactosidase and beta glucuronidase in murine embryos increase 50- to 100-fold in activity between the two-cell and late blastocyst stage. We describe here expression of lysosomal beta galactosidase in preimplantation ovine (two-cell through midblastocyst) and porcine (two-cell through late blastocyst) embryos. Expression of beta galactosidase in ovine and porcine preimplantation embryos followed a similar rate of increase as that described for murine embryos. Activity of beta galactosidase increased over 10-fold between the two- to four-cell and midblastocyst stages in ovine embryos, and 300-fold between the two- to four-cell and late blastocyst stages in porcine embryos. Activity expressed on a per cell basis was relatively constant in ovine embryos, as has been described in murine embryos, and increased approximately 5-fold on a per cell basis in porcine embryos. Activity of beta-galactosidase in ovine and porcine embryos initially was greater than 12-fold on a per cell or per embryo basis than in murine embryos evaluated. The knowledge of beta-galactosidase embryonic expression may provide the basis for preimplantation diagnosis of genetic beta-galactosidase deficiency in these species. PMID- 2112255 TI - Benzodiazepines and their antagonists interfere with opioid-dependent stress induced analgesia. AB - Timing or intensity of shocks significantly modify the characteristics of the analgesia induced by footshock, and conditioning to footshock induces analgesia, independently from the time and shock parameters used for conditioning. However, whatever the parameters of shock, and the presence of conditioning or not, the stress has to be inescapable in order to produce an increase in pain thresholds. This observation suggests that anxiety plays a major role in the development of stress-induced analgesia. In order to test this hypothesis we investigated the effects of the benzodiazepine agonists diazepam and clonazepam, the antagonists RO 15-1788, CGS 8216, CGS 9896, and the inverse agonists FG 7142 and FG 7041 on the development and maintenance of stress-induced analgesia. Benzodiazepine receptor agonists decreased the analgesic effect of inescapable footshock, benzodiazepine receptor antagonists increased the footshock induced analgesia, whereas inverse agonists did not modify the analgesia induced by the shock. All the benzodiazepine receptor ligands blocked the antagonism of the footshock analgesia induced by naloxone. PMID- 2112256 TI - Effects of captopril and SQ29,852 on anxiety-related behaviours in rodent and marmoset. AB - The abilities of the ACE inhibitors captopril and SQ29,852 to modify aversive behaviour was compared to the effects of diazepam in the light/dark exploration test in the mouse, the elevated plus maze and social interaction test in the rat, and in anxiety-related behaviours induced by human threat in the marmoset. In the four tests the acute administration of captopril, SQ29,852 and diazepam had the same profiles of action to reduce aversive responding. This was also observed during chronic administration with the three agents in the mouse. However, withdrawal from a chronic treatment with diazepam precipitated a syndrome of increased aversion, whereas withdrawal from treatment with captopril and SQ29,852 was uneventful, values waning to control levels. Withdrawal from treatment with ethanol, nicotine and cocaine also enhanced aversive responding. Treatment with captopril and SQ29,852 antagonised the behavioural consequences of withdrawal from treatment with diazepam and nicotine and SQ29,852 also blocked the consequences of withdrawal from ethanol and cocaine. It is concluded that captopril and SQ29,852 have an anxiolytic profile of action in 3 species, that cessation of treatment is not associated with a withdrawal syndrome, that the ACE inhibitors cross tolerate with diazepam and can antagonise the behavioural consequences of withdrawal from treatment with drugs of abuse. PMID- 2112257 TI - Motor performance decrement by midazolam: antagonism by Ro 15-1788 and CGS 8216. AB - Rats were trained in a fine motor control performance that required operation by a paw of a force transducer so that it remained between upper and lower limits of a force band for a continuous 1.5-sec period to deliver each food pellet. Acute doses of midazolam (0.75-3.0 mg/kg, SC) impaired indices of motor performance in a graded, dose-related fashion. When administered alone, Ro 15-1788 (0.1-5.0 mg/kg, SC) had no effect on motor behavior while CGS 8216 (0.5 and 1.0 mg/kg, IP) alone had small effects. In general, the motor performance decrements produced by midazolam were antagonized in a dose-related fashion by both Ro 15-1788 and CGS 8216. PMID- 2112258 TI - Enhancing effects of Ro 15-1788 on straw-climbing behavior as measured with the straw-suspension method: reversal by diazepam. AB - Ro 15-1788 (0.5, 1, 5, or 20 mg/kg), a pure benzodiazepine receptor antagonist, was studied for its effect on the duration of immobility and the number of straw climbing attempts in a modified forced-swim test with straw-suspension of rats. A single dose of 20 mg/kg of Ro 15-1788 injected IP prolonged only the duration of immobility with no effect on straw-climbing behavior, whereas both doses of 1 and 5 mg/kg of this compound significantly enhanced the number of straw-climbing attempts in an inverted U-shaped manner. Ro 15-1788 at 1 mg/kg significantly reversed the inhibitory effect of 1 mg/kg of diazepam on the number of straw climbing attempts. It is suggested that the enhancing effect of low doses of Ro 15-1788 on straw-climbing behavior can be regarded as an index of its anxiogenic effect, by acting via central benzodiazepine receptors. PMID- 2112259 TI - Pargyline increases 6-hydroxydopamine levels in the neostriatum of methamphetamine-treated rats. AB - Neostriatal 6-hydroxydopamine (6-OHDA) was detected in 6 of 13 rats pretreated 2 or 4 hr earlier with methamphetamine (MA; 100 mg/kg, SC) and pargyline (25 mg/kg, IP, 30 min before MA injection). Neostriatal 6-OHDA was detected in 2 of 16 rats treated 2 or 4 hr earlier with MA. These results suggest that pargyline pretreatment may enhance formation of 6-OHDA from endogenous stores of dopamine (DA) following MA administration. Alternatively, these results suggest that pargyline pretreatment may protect endogenously formed 6-OHDA from oxidative deamination by monoamine oxidase. Enhancement of MA-induced neostriatal 6-OHDA levels may be the mechanism by which pargyline enhances the long-term neurotoxic effects of MA upon dopaminergic nerve terminals. These observations support the hypothesis that MA toxicity to DA-containing fibers is caused by the conversion of released DA into 6-OHDA. PMID- 2112260 TI - Stacking of three different restriction and modification systems in Lactococcus lactis by cotransformation. AB - Four plasmids encoding restriction and modification (R/M) systems are described that are different in the specificity of their restrictive activity toward the small isometric phage p2 and prolate phage c2. The R/M plasmids were cotransformed into Lactococcus lactis MG1363 with pVS2, encoding resistance to chloramphenicol and erythromycin, to indicate successful transformation events. Analysis of cotransformants showed that three different R/M plasmids could be combined in L. lactis MG1363. The efficiency at which phage plaqued on the transformants decreased as the number of R/M plasmids increased. Some plasmid combinations were unstable suggesting replicon incompatibility. PMID- 2112261 TI - Lithium distribution in mania: single-dose pharmacokinetics and sympathoadrenal function. AB - We examined lithium distribution after a single dose of 25 mEq in 14 drug-free manic patients. Lithium concentrations were measured in plasma, red blood cells, and urine. Maximum concentrations of lithium, times at which they were attained, and influx and efflux rate constants for extracellular fluid, red blood cell, and muscle-like compartments were estimated using a three-compartment pharmacokinetic model. Tissue lithium concentrations may continue to increase for hours after plasma lithium concentrations have peaked. Rate constants for absorption, excretion, and influx and efflux for the tissue compartments were similar to those previously reported for normal subjects. Rate constants for transport into and out of the tissue compartments correlated negatively with norepinephrine or epinephrine excretion and positively with the plasma/red cell Na+ gradient. Rate constants for efflux from red blood cell and muscle compartments correlated with measures of adrenocortical function and were higher in dexamethasone nonsuppressors than in suppressors. These data show that distribution of lithium may be related to sympathodrenal activity and Na+ distribution in manic patients. PMID- 2112262 TI - Blockade of hoarding in rats by diazepam: an analysis of the anxiety and object value hypotheses of hoarding. AB - The "security hypothesis" suggests food hoarding by rats serves to preempt attack and therefore might be motivated by "anxiety". The "object value" hypothesis suggests rats hoard objects that they perceive as valuable as related to some state or need. These hypotheses were evaluated with the anxiolytic drug diazepam, which is purported to both decrease anxiety and increase motivation to eat, and which accordingly either may decrease or increase hoarding. Using a new hoarding paradigm, diazepam (Valium: 0.25-5 mg/kg), was found to produce a dose-related reduction in hoarding that was dependent upon food pellet size and that was reversed by flumazenil (Ro 15-1788), a benzodiazepine receptor antagonist. Diazepam also slowed eating speed, blocked "dodging", a movement used to initiate hoarding, and impaired spatial navigation in a learning-set swimming pool task. The results fail to support the object value hypothesis of hoarding. Since perception of food size, motivation, motor ability and spatial abilities all probably contribute to successful food hoarding, the results provide several explanations other than, or in addition to, anxiety reduction for the drug's effects on hoarding. Nevertheless, the study provides a number of new sensitive measures of the effects of anxiolytic drugs and new insights into their behavioral effects. PMID- 2112263 TI - Medical treatment of acute spinal cord injuries. AB - The injury was performed with 600 g-cm/weight on the spinal cord of 40 cats with T8-9 laminectomy in this study. Ten cats were given 10 mg/kg naloxone i.v. 1 h after injury. Ten cats were given 2 mg/kg thyrotropin-releasing hormone (TRH) i.v. 1 h after injury followed by 1 mg/kg per hour for 4 h. Intravenous lidocaine was begun 30 min after injury in ten cats, administered as 1.5 mg/kg over the initial 5 min, 3 mg/kg over the next 30 min and 1 mg/kg every 30 min for 4 h. The remaining ten cats were given only saline (control group). TRH-treated cats showed significantly better histopathological scores than either naloxone- or lidocaine-treated animals (KW:13.65, P less than 0.50). PMID- 2112264 TI - Influence of gonadal steroids on rat pituitary growth hormone secretion. AB - Growth hormone (GH) secretion increases at the time of puberty, and both androgens and estrogens increase the GH response to provocative agents. Little is known, however, with regard to the mechanism or site of action of gonadal steroid stimulated GH secretion. Using monolayer primary cell culture and radioimmunoassay techniques, insulin-like growth factor I (IGF-I), purified and biosynthetic human GH, 17 beta-estradiol (E2), and testosterone (T) effects on GH release from rat anterior pituitary cells were investigated. Media content of rat GH was measured, both basally and after growth hormone releasing factor (GRF) stimulation. IGF-I at 50 nM concentration inhibited basal rGH release but not in GRF-stimulated cells. E2 (10 pM) stimulated basal secretion of rGH, although higher concentrations did not. High concentrations of T (100,000 pM) caused an increase in GRF-stimulated rGH secretion. Neither purified nor biosynthetic hGH pretreatment influenced subsequent rGH release. These results suggest that IGF-I inhibits and E2 (low dose) and T (high dose) augment rGH release in part at the level of the anterior pituitary. PMID- 2112265 TI - [Muscle structure and aerobic performance capacity in recruit training school]. AB - The aerobic performance capacity (VO2 max) and muscle ultrastructural composition was analyzed in 18 subjects undergoing basic training in the Swiss army. Three groups were selected based on their sports activity. Group S contained subjects that had a previous systematic background in sports activities and trained regularly at least three times per week. A second group consisted of subjects that had no previous training and were subjected to an additional, individually adjusted endurance exercise (three times per week) for the first 8 weeks of their service period (group T). The control group (C) had no previous training and followed only the regular military duties. VO2 max was found to be significantly higher in group S at the beginning of the military service. However, VO2 max did not change significantly during the service period in any of the groups, Muscle mitochondria showed a significant change (+19%) only in group T. Heart rate recordings indicated that despite "strenuous" military activity, heart rates rarely reached levels sufficient for an increase in aerobic performance capacity. PMID- 2112266 TI - Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. AB - Major histocompatibility class I proteins display viral and self antigens to potentially responsive cells and are important for the maturation of T cells; beta 2-microglobulin (beta 2M) is required for their normal expression. Mouse chimeras derived from embryonic stem cells with a disrupted beta 2M gene transmitted the inactivated gene to their progeny. Animals homozygous for the mutated beta 2M gene were obtained at expected frequencies after further breeding. The homozygotes appeared normal, although no class I antigens could be detected on their cells and the animals are grossly deficient in CD4- CD8+ T cells, which normally mediate cytotoxic T cell function. PMID- 2112267 TI - Light pulses that shift rhythms induce gene expression in the suprachiasmatic nucleus. AB - Lighting cycles synchronize (entrain) mammalian circadian rhythms by altering activity of cells in the suprachiasmatic nucleus (SCN) of the hypothalamus, a circadian pacemaker. Exposure of hamsters and rats to light pulses at those phases of the circadian rhythm during which light can shift the rhythm caused increased immunoreactivity for the product of the immediate-early gene c-fos in cells in the region of the SCN that receives retinal fibers. Light pulses also increased messenger RNA for the Fos protein and for the immediate-early protein NGFI-A in the rat SCN. Similar increases in mRNA for NGFI-A were seen in the SCN of hamsters. Thus cells in this portion of the SCN undergo alterations in gene expression in response to retinal illumination, but only at times in the circadian cycle when light is capable of influencing entrainment. PMID- 2112268 TI - An evaluation of the potential of HBED as an orally effective iron-chelating drug. PMID- 2112269 TI - Case of the season. Malignant neurogenic tumor of duodenum and pancreas. PMID- 2112270 TI - MR of central nervous system neoplasia of the phakomatoses. PMID- 2112271 TI - Effect of aspirin and dipyridamole treatment on prostacyclin production by human veins. AB - Patients admitted for surgical removal of varicose veins were treated in a blinded manner for 48 hours prior to surgery with either placebo, low-dose aspirin (25 mg twice daily), dipyridamole (150 mg twice daily) or both. Segments of vein excised at surgery were incubated with or without sodium arachidonate and subsequent prostacyclin (PGI2) production was measured without knowledge of treatment given. During the first 5 minute period of incubation in the presence of arachidonate, veins from dipyridamole-treated patients demonstrated increased (by 75%) arachidonate-stimulated PGI2 production compared to placebo-treated patients. By contrast, PGI2 production was reduced by 64% by aspirin treatment and 67% by aspirin plus dipyridamole compared to placebo-treated patients (p = less than 0.05). In unstimulated vein segments incubated in the absence of arachidonate, spontaneous PGI2 production during the first 5 minute incubation period was increased 32% following dipyridamole treatment but was unchanged following aspirin treatment. By contrast, unstimulated (spontaneous) PGI2 production in patients treated with aspirin plus dipyridamole was reduced by 57% (p = less than 0.05), compared to both placebo- and aspirin-treated patients, and by 71% (p = less than 0.05) compared to dipyridamole-treated patients. With repeated change of incubation medium, the ability of vein walls to produce PGI2 declined. This exhaustion was not prevented by drug treatment. However, drug effects between patient treatment groups were consistent over successive incubation periods. These results suggest that certain therapeutic benefits that might be achieved by enhancement of PGI2 production from vascular endothelium following dipyridamole treatment may be reduced by simultaneous aspirin treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112272 TI - A new platelet function test. AB - A method for screening EDTA(K3) blood samples for platelet function is described. The general availability of whole blood platelet counters in the clinical laboratory suggested their use to measure platelet aggregation. To simplify the collection and storage of blood samples, a method utilizing EDTA collected blood is described. Addition of calcium and citrate restores platelet function to blood samples even when stored at room temperature for several hours. Thus, the blood sample used to assay RBC, WBC and platelet parameters may also be employed in platelet aggregation. A comparison of this method with aggregometry on 120 subjects indicated a similar response to arachidonate, collagen, ristocetin and ADP. PMID- 2112273 TI - [The use of genetic engineering in veterinary medicine with examples from epidemiology, diagnosis and drug production]. AB - The results of genetic engineering have reached practical veterinary medicine already. Nevertheless there is a great lack of knowledge among those veterinarians who usually do not work with these methods. Therefore we want to give an introduction into the advantages and dangers of this technology concerning veterinary medicine. Some important analytical methods are explained. Related viruses such as WEE and EEE or canine parvovirus, feline parvovirus and mink enteritis virus, or the related coronaviruses FIPV and TGEV serve as examples for the possibilities in molecular diagnosis and epidemic monitoring. The history of the gl- mutants of PRV, now prescribed as vaccine strains in the FRG, is an example of the development of genetic engineered vaccines. A new generation of vaccines based on recombinant vaccinia viruses is imminent. Thus we have to be aware of the high risks and responsibility of everybody who is involved in these new systems, especially the scientist who produces genetically altered organisms. PMID- 2112274 TI - Aflatoxin production in cultures of Aspergillus flavus incubated in atmospheres containing selected cotton leaf-derived volatiles. AB - Aspergillus flavus, in solid culture, was exposed to individual selected, commercially obtained volatile compounds that were similar to volatile cotton leaf-derived components. The radial growth pattern of A. flavus and the production of aflatoxin were determined on these volatile exposed cultures. The most bioactive compounds C6-C9 alkenals, completely inhibited the growth of the fungus. Unexpected results demonstrated that 3-methyl-1-butanol and 3-methyl-2 butanol inhibited A. flavus growth by 20% but increased production of aflatoxin B1 by 1.5 to 2-fold. Other relationships of growth and aflatoxin production resulting from exposure to the bioactive volatiles are discussed. PMID- 2112275 TI - Changes in the concentrations of cerebral proteins following occlusion of the middle cerebral artery in rats. AB - Using an immunoblotting technique, we investigated changes in the concentrations of microtubule-associated protein 2, 200-kDa neurofilament, tubulin, myelin associated glycoprotein, and 2':3'-cyclic nucleotide 3'-phosphodiesterase in the brains of 40 rats following occlusion of the left middle cerebral artery or sham operation. Compared with those 4 hours after surgery, concentrations of all proteins decreased significantly in the left hemisphere 3 days after surgery (p less than 0.01). Microtubule-associated protein 2 was the most susceptible to ischemia, and its mean +/- SEM concentration decreased to 23 +/- 9.4% of that in concurrent sham-operated controls. Degradation products of microtubule-associated protein 2 and myelin-associated glycoprotein were detected on the blots. Furthermore, in the contralateral hemisphere (where calpain might be activated), concentrations of these two proteins decreased to 57 +/- 12.0% and 83 +/- 4.3% of those in concurrent sham-operated controls, respectively, 3 days after surgery. Changes in the concentrations of cerebral proteins in the contralateral hemisphere are important for understanding clinical symptoms not attributable solely to the ipsilateral lesion following a focal cerebral stroke. PMID- 2112276 TI - Carbamazepine metabolism in humans: effect of concurrent anticonvulsant therapy. AB - Free and total carbamazepine (CBZ) and carbamazepine-epoxide (CBZ-EP) plasma levels were obtained on 113 patients with epilepsy (18-61 years old) controlled on either monotherapy or coadministration with either phenobarbital (PB), phenytoin (PHT), valproic acid (VPA), or all three. A subset of patients were administered tetradeuterium labeled CBZ to evaluate the effects of autoinduction and coadministration of VPA on the kinetics of CBZ and its metabolite CBZ-EP. Polytherapy had variable effect on free and total CBZ plasma levels compared to monotherapy. Coadministered PHT (co-PHT), or all three anticonvulsants together (PHT, PB, and VPA: co-AEDs) decreased free and total CBZ plasma levels. No change was noted for coadministered VPA (co-VPA). Compared to monotherapy the free and total CBZ-EP levels increased with co-VPA, less with coadministered PB (co-PB), and no change with co-PHT or co-AEDs. Protein binding of CBZ and CBZ-EP was not affected by any antiepileptic drugs studied. The free and total CBZ-EP/CBZ ratio was tripled with co-VPA or co-AED's, and doubled with co-PHT or co-PB. Isotope labeling did not demonstrate any differences in half-life (t1/2), plasma clearance (Cl), or volume of distribution (Vd). Compared to naive controls, monotherapy and co-VPA decreased CBZ t1/2 by 50%, and more than doubled the CBZ Cl without a significant change in the Vd. Autoinduction is one explanation for these changes with chronic CBZ therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112277 TI - Evaluation of the polyethylene glycol-potentiated indirect antiglobulin test. AB - Results of the indirect antiglobulin test (IAT) potentiated by the addition of polyethylene glycol (PEG) were compared with those of the IAT performed with bovine serum albumin (BSA). This retrospective study, which encompasses 3 years, confirms that use of PEG-IAT increases the rate of detection of clinically significant red cell (RBC) antibodies, decreases the detection of insignificant antibodies, reduces the need to use other serologic enhancement techniques (such as enzyme modification of RBCs), and has a positive impact on the laboratory's workload. These advantages are provided with no diminution in the quality of service provided by the blood bank. PMID- 2112278 TI - Blood screening for non-A, non-B hepatitis by hepatitis C virus antibody assay. AB - Hepatitis C virus (HCV) antibody was detected in 1499 donor sera by radioimmunoassay using an antigen expressed in yeast from a cDNA clone of the HCV genome. Eighteen samples over 4200 counts per minute (cpm) were considered to contain infectious HCV because these recipients developed typical posttransfusion non-A, non-B hepatitis after transfusion. The antibody-positive sera were all within the normal range of ALT levels. This assay system is thus useful for the screening for blood transfusion. PMID- 2112279 TI - Hepatitis C look-back: our next challenge. PMID- 2112280 TI - Correction of prolonged bleeding time in von Willebrand's disease with Humate-P. PMID- 2112281 TI - Anti-hepatitis C virus in blood donors with raised ALT levels. PMID- 2112282 TI - Cyclosporine monitoring in liver allograft recipients: two distinct patterns of blood level derangement associated with nephrotoxicity. AB - The parallel measurement of specific and nonspecific CyA levels by second generation radioimmunoassays based on monoclonal antibodies proved to be an effective procedure to monitor both parent CyA levels and the capacity to eliminate its metabolite. Using this monitoring procedure it could be shown that CyA-associated nephrotoxicity in the early course after liver transplantation is associated with two distinct patterns of blood level derangement. One pattern is characterized by increased parent drug levels, the other by an increased metabolite concentration resulting from severely disturbed CyA metabolite excretion. This raises the possibility that not only the parent drug but also some of its metabolites may exert nephrotoxic effects when present in excessively high concentrations. This finding provided the rationale for a therapeutic CyA monitoring regimen taking into account both specific and nonspecific measurements. In liver transplant patients monitored according to this regimen and treated with quadruple immunosuppression the incidence and severity of CyA associated nephrotoxicity was markedly reduced. The metabolite-associated type of nephrotoxicity was only found in patients with severely disturbed liver function. PMID- 2112283 TI - Mechanical circulatory support systems: ethical considerations. PMID- 2112284 TI - The private sector vis-a-vis government in future funding of organ transplantation. PMID- 2112285 TI - Suppression of chicken J chain production by in ovo bursectomy. AB - The influence of in ovo bursectomy on the levels of J and mu chains in the sera of embryonic and hatched chicks was studied by the dot blotting immunoassay. The results indicated a decrease in the level of J chains during the embryonic stage after treatment with testosterone compared with normal chicks. Testosterone treatment caused a decrease in J-chain levels after hatching which was more marked in reduced-alkylated than in non-reduced sera. In contrast, testosterone caused no significant change in serum levels of mu chains, either in ovo or after hatching. Our findings further present the paradox that although removal of the bursa of Fabricius by testosterone treatment did not impair mu-chain synthesis, B cell differentiation was suppressed. These observations indicate that in ovo bursectomy selectively inactivates B-cell differentiation as indicated by the induction of immunodeficiency, and results in the failure of J-chain production. PMID- 2112287 TI - Immunogenicity of subcellular fractions of Brucella abortus: measurement by in vitro lymphocyte proliferative responses. AB - Five groups of heifers were immunized with various subcellular fractions of Brucella abortus and tested for their responsiveness in lymphocyte proliferative responses in vitro. The five subcellular fractions used as immunogens were: (1) a mixture of recombinant outer membrane proteins fused to Escherichia coli beta galactosidase, (2) a mixture of outer membrane proteins BaomI, BaomIIB1, and BaomIII1, (3) a mixture of outer membrane proteins 7.5 kDa and 8.8 kDa, (4) a complex of smooth lipopolysaccharide and proteins, and (5) a complex of outer membranes and peptidoglycan (OM-PG complex) from a rough strain. All immunogens were emulsified in adjuvant and administered twice at a 61-day interval. Two other groups of cows were included; one immunized with strain 19 and the other with adjuvant only. Strain 19 and the rough OM-PG complex induced responsiveness in lymphocyte proliferation assays in a high percentage of immunized cows. The smooth lipopolysaccharide-protein complex induced responsiveness in fewer cows. The lowest frequencies of responding cows were found in groups that received either recombinant proteins or purified protein mixtures. Based on these results, we concluded: (1) cellular immunity, as measured by in vitro lymphocyte proliferative responses, can be induced with subcellular fractions of B. abortus and (2) the more complex the immunogen, the greater the frequency of responding cows. PMID- 2112286 TI - Production and characterization of monoclonal antibodies specific for bovine gamma-interferon. AB - Nine stable hybridoma cell lines were established which secreted specific monoclonal antibodies (MAbs) to bovine gamma-interferon (BoIFN-gamma). Specific binding of each of the MAbs to recombinant BoIFN-gamma (rBoIFN-gamma) was demonstrated in an indirect ELISA, whilst none of the MAbs bound to rBoIFN-alpha or rBoIFN-beta. In a Western blot the MAbs reacted with the 16 kDa and 32 kDa polypeptides present in rBoIFN-gamma preparations. Competitive ELISA's showed that four MAbs bound to one epitope on rBoIFN-gamma, and the other five MAbs bound to a separate epitope. Two MAbs, each recognising different epitopes, were shown to neutralise the anti-viral activity of natural BoIFN-gamma. PMID- 2112288 TI - The trivia champ and honorary faculty member. PMID- 2112289 TI - Age-related changes in biotransformation of azoxymethane and methylazoxymethanol in vitro. AB - 1. Age-related changes in hepatic hydroxylation of azoxymethane (AZO) to methylazoxymethanol (MAM), as well as colonic phase I metabolism of MAM by alcohol dehydrogenase (ADH) were examined in young (2-4 months), middle-aged (12 14 months), and old (22-24 months) male Fischer 344 rats. In addition, the possibility that colonic glucuronyltransferase might be involved in the biotransformation of MAM was also investigated. 2. A significant decrease in hepatic conversion of AZO to MAM was found in old vs young rats, concomitant with a decrease in hepatic cytochrome P-450 content, while no age-related difference was found in the colonic metabolism of MAM by ADH. MAM inhibition of colonic 4 methylumbelliferone glucuronyltransferase was non-competitive, suggesting indirectly that colonic glucuronyltransferase is not involved in conjugation of MAM. 3. It is concluded that ageing in the male Fischer 344 rat results in alternations of AZO and MAM biotransformation which indicate that AZO may be less carcinogenic in older rats. PMID- 2112290 TI - The use of single sample clearance estimates to probe hepatic drug metabolism: handprinting the influence of cigarette smoking on human hepatic drug metabolism. AB - 1. Conditions were examined under which estimates of drug clearance made from a single measurement of plasma concentration effectively represented multiple sample estimates of clearance for quinidine, valproic acid, unbound valproic acid, and lorazepam. When plasma concentrations were measured at various post dose times, both individual and mean values of single-sample clearance estimates, CL, corresponded closely to multiple-sample clearance estimates. Best post-dose sampling times were: quinidine, 8 h; valproic acid, 24 h; and lorazepam, 24 h. 2. Single-sample clearance estimates, CL, were calculated for seven drugs employed as probes of human hepatic drug-metabolizing enzymes. Valproic acid was used to probe microsomal and peroxisomal beta-oxidase activity; antipyrine, phenytoin, quinidine, carbamazepine, and theophylline were used as probes of hepatic mixed function oxidases (MFO), and lorazepam as a probe for UDP-glucuronosyltransferase activity. 3. A clearance index (CI, namely probe CL for smokers divided by probe CL for non-smokers) was calculated for each probe. The effect of cigarette smoking (and presumably polycyclic aromatic hydrocarbon exposure) on all probe CL values was consolidated and plotted as the logarithm of the CI to produce a handprint of drug metabolizing enzyme activity for cigarette smokers. 4. Only theophylline CL was significantly faster among smokers than non-smokers (P less than 0.01). 5. We conclude that the use of multiple probes of MFO activity when given in a single-dose, single-sample protocol for structuring handprints represents a minimally invasive and useful approach to characterize xenobiotic mediated effects on hepatic MFO. PMID- 2112291 TI - [Monitoring respiratory and circulatory parameters in comparing various jet ventilation procedures]. AB - Reported is a system of apparatures to control characteristic changes of cardiorespiratory function during different methods of endoscopic ventilation. The aim of the study is to measure and record simultaneously and continuously ECG, thoracic movement, tracheal pressure, pulmonary artery pressure and arterial oxygen pressure using transcutaneous technique. Measurements of arterial blood pressure and blood gas analysis (PaO2, PaCO2, BE, HCO3-, pH) are carried out in intervals. Four different methods of injector-ventilation are compared with the conventional laryngoscopic ventilation on the basis of a test program. Laryngoscopic ventilation as well as injectorventilation by CARDEN-Tubus make it possible to achieve a hyperoxaemic situation by normofrequent ventilation. Despite of hyperventilation it is not possible in every case to achieve an increased capillary oxygen pressure of 200 to 300 mm Hg by injector-ventilation with Venturi effect because of a smaller oxygen proportion. In jet-ventilation with N2O/O2-mixture (3:1) there is no appreciable hyperoxia, but a small reduction of systemic arterial blood pressure. With all techniques of mechanical respiration usual middle intratracheal pressure of respiration was not exceeded. Traumatic pressure of jets was only indirectly shown in steep rises of pressure by the applied technique of measurement. PMID- 2112292 TI - RNA probes detect nucleotide sequence homology between members of two different nairovirus serogroups. AB - Cloned cDNA derived from the small (S) and medium (M) genomic RNA segments of Dugbe (DUG) virus, isolate ArD44313, a member of the Nairobi sheep disease (NSD) serogroup of nairoviruses (family, Bunyaviridae) was used to prepare 32P-labelled DNA and RNA probes. The S and M segments of six isolates of DUG virus all hybridised to both DNA and RNA probes, although the M segment of isolate KT281/75 reacted only weakly. Of nine other nairoviruses tested, representing all the six other serogroups within the Nairovirus genus, none hybridised to the DNA probes. However, under conditions of low stringency, the DUG S and M RNA probes hybridised to the respective S and M segments of Ganjam (GAN) virus (another member of the NSD serogroup). The DUG S RNA probe also hybridised to the S segments of Crimean-Congo haemorrhagic fever (CCHF) virus and Hazara (HAZ) virus (members of the CCHF serogroup). The indicated sequence relationships between DUG, GAN, CCHF and HAZ viruses show that the NSD serogroup is more closely related to members of the CCHF serogroup than it is to nairoviruses of the other five serogroups. PMID- 2112293 TI - Oscillatory CO2 evolution in glycolysing yeast extracts. AB - The rate of formation of carbon dioxide in cytoplasmic yeast extracts in an open system with continuous infusion of glucose was measured by membrane inlet mass spectrometry during glycolytic oscillations. The rate of CO2 production rose in the first third of each cycle to a maximum of about 100 mumol per ml yeast extract per hour and subsequently diminished to a final level of about 50 mumol per h. Measurements of the NADH light absorption under the same conditions revealed oscillations of relaxation type. The phase of high CO2 production could be related to the phase of the high NADH level, giving evidence that the flux in glycolysis is increased during the phase of high NADH concentration. Only half of the amount of injected glucose was metabolized to CO2 during the sustained oscillation, although free glucose did not accumulate. PMID- 2112294 TI - Surgical management of duodenal diverticula. AB - Surgical treatment of duodenal diverticula, although infrequently indicated, implies a high risk of postoperative complications. Diverticuloplasty was performed on five patients, four of whom had biliary or pancreatic duct obstruction and also underwent cholecystectomy and sphincteroplasty. The fifth patient had chronic abdominal pain. Complications occurred in three cases- postoperative diverticular bleeding, retroperitoneal hematoma and peroperative perforation of the common bile duct. The long-term results (3-10 years) were excellent in all cases. PMID- 2112295 TI - Cerebral blood flow reactivity in spontaneously breathing, preterm infants shortly after birth. AB - In 18 spontaneously breathing, preterm infants (mean gestational age 30.3 weeks) cerebral blood flow (CBF) was investigated twice, 2 and 3 hours after birth when spontaneous changes in arterial carbon dioxide tension (PaCO2) and mean arterial blood pressure (MABP) were expected. Transcutaneous oxygen tension (TcO2) was kept normal by adjusting the inspiratory oxygen fraction. In 12 infants, plasma adrenaline and noradrenaline were constant throughout the study. Changes in CBF infinity (CBF infinity) were significantly related to changes in PaCO2 (p = 0.0001) whereas neither changes in MABP nor TcO2 reached a significant association to changes in CBF infinity (p = 0.67 and p = 1.0, respectively). The calculated CBF infinity -CO2 reactivity of 28.9% per kPa PaCO2 (95% confidence interval 16.1-43.0) is comparable to findings in older newborns and healthy adults. Only one of 18 infants developed germinal layer haemorrhage (grade I) in spite of the hypercapnic state which was observed during the first hours of life. Periventricular leucomalacia was not detected. It is suggested that the cerebral blood flow is well regulated within physiological variations of PaCO2 and MABP in the healthy, preterm newborn even shortly after birth. PMID- 2112296 TI - Small bowel permeability to 51Cr-EDTA in children with recurrent abdominal pain. AB - Small bowel permeability was investigated in 87 children with recurrent abdominal pain by measuring the 24-h urinary excretion of orally administered 51Cr-EDTA. The mean excretion was 3.64% +/- 1.49% per 24 h. The difference between the mean urinary excretion in children with recurrent abdominal pain and control children (2.51% +/- 0.70%), was significant (p less than 0.01, two sample t-test). The increased small bowel permeability in children with recurrent abdominal pain might indicate an intestinal etiology for the patients' complaints. PMID- 2112297 TI - Reduced glomerular filtration and elevated urinary protein excretion in diabetic ketoacidosis. AB - Glomerular filtration rate (GFR) was measured by two methods in 9 children with diabetic ketoacidosis (DKA), directly by true creatinine clearance and indirectly by means of serum beta-2-microglobulin levels. We found significantly reduced GFR in the first hours of DKA. The rapid improvement in GFR after fluid and electrolyte replacement indicates that volume depletion is the major cause of low filtration rate. In spite of the reduced GFR we observed pronounced albuminuria and low molecular weight (LMW) proteinuria. We conclude that the pathological albuminuria and microalbuminuria in DKA are caused not by glomerular hyperfiltration but by tubular dysfunction. PMID- 2112298 TI - Growth hormone response to GHRH 1-44 in the diagnosis of growth failure. PMID- 2112299 TI - Genetic regulatory hierarchy in Caulobacter development. PMID- 2112300 TI - Genetic control of sex determination in Drosophila. PMID- 2112301 TI - Role of the zerknullt gene in dorsal-ventral pattern formation in Drosophila. PMID- 2112302 TI - Mechanisms of a cellular decision during embryonic development of Drosophila melanogaster: epidermogenesis or neurogenesis. PMID- 2112303 TI - Somatic diversification of the chicken immunoglobulin light-chain gene. AB - The bursa of Fabricius provides a unique organ for the study of lineage-specific development in a multicellular organism. Unlike mammalian B cells, B cells in the chicken develop in a single wave of differentiation, beginning with the commitment of progenitor cells to the B cell lineage between days 10 and 15 of embryogenesis. By day 18 of embryogenesis, all lymphoid progenitor cells capable of differentiation along the B cell lineage have migrated to the bursa of Fabricius. Following migration to the bursa, these lymphoid progenitors enter exponential growth and begin to populate each of the 10(4) bursal follicles. Between day 18 of embryogenesis and 2-4 weeks of age, B cells undergo a stage of bursal-dependent differentiation. By the end of this period, chickens are able to mount primary immune responses against virtually all antigens. In addition, by this time sufficient numbers of B cells have migrated from the bursa to peripheral lymphoid organs so that the B cell immune system can be maintained even if the bird is bursectomized. Bursectomy of chicks after 4 weeks of age has no long-term effects on the development and maintenance of the B cell immune system in adult birds. Because of the central nature of the surface Ig molecule to B cell development in mammals, the chicken IgL gene locus has been intensively studied during avian B cell development. The chicken IgL locus is a particular interest because it has only one V region capable of rearrangement. Rearrangement of the IgL gene is not dependent on the bursal environment. B cell progenitors rearrange their IgL gene between days 10-15 of embryogenesis, prior to migration to the bursa. IgL gene rearrangement occurs by a deletional mechanism in which a precise joining of the IgL recombination signal sequences leads to a circular episomal element. During this deletion it appears that single nonrandom bases are added to both the V and J coding segments. Subsequent V-J joining occurs at random. Most progenitor B cells appear to rearrange only a single IgL allele. The high frequency of in-frame alleles observed in avian B cell lines appears to result from the selective amplification of cells with productive IgL rearrangements during bursal development between days 12 and 18 of embryogenesis. To create an immunological repertoire, chickens must diversify the coding sequence of this single functional V gene segment during development.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2112304 TI - Features of the cerebral vascular pattern that predict vulnerability to perfusion or oxygenation deficiency: an anatomic study. AB - In an ongoing study of brain microvasculature in humans at autopsy, we had the opportunity to analyze the overall scheme of this vascular supply. The native endothelial membrane enzyme, alkaline phosphatase, is used to precipitate black lead sulfide salt in the vessel wall, rendering the brain microvasculature visible by both light microscopy and microradiography. There are six distinct patterns of intraparenchymal afferent blood supply to the supratentorial brain: short arterioles from a single source (e.g., those in the cortex); short- to intermediate-length arterioles, single source (anterior two-thirds of the corpus callosum); short- to intermediate length arterioles and arteries, dual source (subcortical U fibers); intermediate-length arterioles and arteries, triple source (extreme/external capsule and claustrum); long arteries and arterioles, single source (centrum semiovale); and large, long muscular arteries, single source (thalamus and basal ganglia). The nature of this arrangement offers some protection to certain regions of the cerebrum from circulatory challenges such as hypotension, while leaving other areas vulnerable. The distal arterioles supplying two of these protected regions, the U-fiber area and the extreme/external capsule and claustrum area, also exhibit the feature of interdigitation, which can offer additional collateral potential from one arteriolar territory to the next. Aging, hypertension, diabetes mellitus, and atherosclerosis can have a significant impact on brain microcirculation. The way in which vascular patterns dictate the distribution of these effects is discussed. The ability to stain the cerebral microvessels and demonstrate the finer points of their patterns in sections and microradiographs has enabled us to resolve some long-standing questions about vascular connections and directions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112305 TI - Use of acetazolamide-challenge xenon CT in the assessment of cerebral blood flow dynamics in patients with arteriovenous malformations. AB - Arteriovenous malformations (AVMs) may cause symptoms related to a reduction of cerebral blood flow (CBF) to surrounding brain parenchyma. To evaluate this compromise of hemodynamic reserve (commonly referred to as steal phenomenon), we used acetazolamide challenge and stable-xenon CT (Xe/CT). Baseline Xe/CT studies in 13 patients with AVMs were followed by an acetazolamide challenge to the vascular reserve. Blood flow maps were quantitated by using region-of-interest (ROI) software. ROI findings were categorized into four groups on the basis of the presence or absence of normal baseline CBF and presence or absence of normal augmentation of CBF. ROIs were designated as near site (within the vascular territory supplying the AVM) or far site (outside the vascular territory supplying the AVM). One patient had a normal baseline and normal augmentation of CBF (group 1). The other patients had a combination of one or more of the other three categories. Ten patients had parenchymal areas that exhibited either a normal or low baseline CBF with decreased augmentation; both conditions were interpreted as decreased vascular reserve (groups 2 and 3). Eleven patients had parenchymal areas that showed a low baseline CBF and normal augmentation with acetazolamide (group 4), interpreted as having a decreased demand for CBF but having a normal vascular reserve. Decreased vascular reserve was found in 27% of the nearsite areas and 17% of the far-site areas. No patients had only far-site abnormal vascular reserve. We believe that compromised vascular reserve can best be evaluated with a challenge study, such as this acetazolamide-challenge Xe/CT study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112306 TI - Intracranial aneurysms: evaluation by MR angiography. AB - The purpose of this study was to compare the accuracy of a volume gradient-echo MR angiography (MRA) technique with that of intraarterial digital subtraction angiography (IA DSA) in the identification of intracranial aneurysms. The intracranial vasculature was examined in 47 patients by MRA and compared with IA DSA findings in 19 of these patients who had saccular or giant intracranial aneurysms. The remaining 28 patients, in whom no aneurysm was found, served as a control group. MRA was performed with the use of a velocity-compensated gradient echo sequence (TR = 40-50/TE = 7-15) with a 15 degree flip angle. The sensitivity and specificity were calculated for the evaluation of the cine 3D reconstructions (cine MRA) only, cine MRA + inspection of the individual partitions, and cine MRA + individual partitions + spin-echo studies. Of 21 aneurysms, of which three were missed in two patients, the sensitivity varied from 67% for cine MRA only to 86% for the cine MRA + partitions + spin-echo studies; of the 19 patients, among whom it was assumed that the diagnosis of any one aneurysm in a patient would lead to angiography and detection of additional aneurysms, the sensitivity varied from 73% for the cine MRA only to 95% for the cine MRA + partitions + spin-echo studies. The results of this study suggest that MRA can define the circle of Willis sufficiently to allow detection of intracranial aneurysms as small as 3-4 mm. MRA holds promise as a truly noninvasive screening examination of intracranial vasculature in patients at risk for aneurysms. PMID- 2112307 TI - Three-dimensional phase-contrast MR angiography in the head and neck: preliminary report. AB - Morbidity and possible mortality associated with contrast angiography lead to its cautious use. A noninvasive method for screening and further delineating known abnormalities would be welcomed. This article reviews the initial results and application of MR imaging to vascular imaging in the head and neck. By using the three-dimensional phase-sensitive method of Dumoulin, Souza, and collaborators, we acquired MR angiograms in 37 min and portrayed blood flow in all the major arteries and veins. Feeding arteries and draining veins of arteriovenous malformations were well delineated; aneurysms as small as 3-4 mm were shown, and obstructed cerebral vessels and the patency of a highly stenotic internal carotid artery were demonstrated. MR angiography of the head or neck offers great promise as a noninvasive means of studying vascular abnormalities. PMID- 2112308 TI - Routine MR imaging of the internal carotid artery siphone: angiographic correlation with cervical carotid lesions. AB - This study correlates the appearance of the cavernous segment of the carotid artery on MR images with the presence of significant stenosis or occlusion of the cervical carotid artery as seen on angiograms in 100 patients who had brain MR imaging and arteriography within a 1-week period. Four patients demonstrated isointense signal within the carotid artery's cavernous segment; two of these findings correlated with complete carotid occlusion as seen angiographically, while partial compromise was seen angiographically in the other two. Four other patients had variable signal intensity and irregularity of the luminal outline in the carotid siphone, correlating with angiographic evidence of atheromatous disease in three patients and of dissection in one patient. The demonstration of normal signal void within a normal-appearing cavernous segment of the internal carotid artery in the remaining 92 patients correlated with absence of significant stenosis within the cervical segment in 86 patients. In the remaining six, significant disease of the internal carotid artery was found. Isointensity within the intracranial carotid artery can indicate either complete occlusion or very slow flow. Therefore, angiography is still necessary to completely exclude potentially treatable disease that produces very slow flow leading to isointensity. The presence of normal flow void in the intracranial segment does not exclude significant compromise of the cervical segment of the carotid artery. PMID- 2112309 TI - Hyperdense middle cerebral artery sign on CT: efficacy in detecting middle cerebral artery thrombosis. AB - The hyperdense middle cerebral artery sign is a CT predictor of the development of a large cerebral infarct. The limits of detectability were tested in a blinded, then unblinded analysis of CT scans from 25 acute stroke patients. In the initial blinded analysis, sign detection exhibited the following mean values: sensitivity, 78.5%; specificity, 93.4%; positive predictive value, 66%; negative predictive value, 96.4%; accuracy, 91.3%. Kappa statistics analysis indicated poor interobserver agreement (k = .38). Results of unblinded analysis were as follows: sensitivity, 69%; specificity, 94.4%; positive predictive value, 82.8%; negative predictive value, 88.7%; accuracy, 87.3%. There was fair unblinded interobserver agreement (k = .53). Unblinded analysis had a lower false-positive frequency and did not increase the number of true-positive determinations. We conclude that detection of the hyperdense middle cerebral artery sign on CT scans by multiple observers is a sensitive, accurate, and predictive indicator of middle cerebral artery thromboembolism. PMID- 2112310 TI - Lyme disease of the CNS: MR imaging findings in 14 cases. AB - The MR images of 14 patients with clinical diagnoses of Lyme disease, CNS complaints, and positive Lyme titers were reviewed. MR examinations were abnormal in 43%. Areas of abnormal signal were identified within the cerebral white matter as well as within the brainstem. PMID- 2112311 TI - Biopsy-confirmed CNS Lyme disease: MR appearance at 1.5 T. PMID- 2112313 TI - Multiple sclerosis in adolescents: CT and MR findings. AB - The MR and CT findings in 12 adolescents with multiple sclerosis were compared with reported findings in adults. The adolescent group showed a more striking female predominance, more severe disease characteristics, and more frequent infratentorial involvement. Cortical atrophy and abnormal iron accumulation in the basal ganglia were uncommon in the adolescents. Neither group demonstrated a correlation between symptom severity and either extent or location of disease as delineated by MR imaging. MR was more sensitive than CT in detecting demyelinating plaques. PMID- 2112312 TI - Leukoencephalopathy in cerebral amyloid angiopathy: MR imaging in four cases. AB - We report four cases of biopsy proved cerebral amyloid angiopathy demonstrated by MR imaging. White matter signal hyperintensities on T2-weighted spin-echo pulse sequences were present in three patients. We believe the white matter lesions associated with cerebral amyloid angiopathy are not specific to this disorder but rather reflect hypoperfusion of distal white matter resulting from vascular disease. PMID- 2112314 TI - MR imaging of the brain in five members of a family with Pelizaeus-Merzbacher disease. AB - MR imaging was performed in five members of a family afflicted with Pelizaeus Merzbacher disease. The individuals imaged included a male proband, his mother, and three maternal uncles. Clinically affected members showed generalized white matter signal aberration consistent with dys- and demyelination, basal ganglia, and thalamic signal aberration suggestive of pathologic iron storage and diffuse brain atrophy. These findings are similar to those seen in other leukodystrophies. The proband's mother was normal by neurologic examination but showed a suspicious but not definitely abnormal similar pattern of basal ganglionic and white matter signal aberration. In our limited patient sample, MR appears to be able to: (1) demonstrate a pattern of imaging abnormalities characteristic of Pelizaeus-Merzbacher disease (we do not know if this pattern is specific); (2) potentially detect the obligate carrier state; and (3) detect the facultative carrier state. PMID- 2112315 TI - Preoperative embolization of cerebral arteriovenous malformations with polyvinyl alcohol particles: experience in 51 adults. AB - In order to determine possible risk factors and to assess the value of platinum microcoils added to polyvinyl alcohol particles in preoperative embolization of cerebral arteriovenous malformations in adults, we reviewed our experience with this procedure. Between September 1985 and June 1989, we performed embolizations in 54 patients with cerebral arteriovenous malformations. Of these, procedures in 51 adults involved the use of polyvinyl alcohol particles, either alone (n = 29) or in combination with platinum microcoils (n = 21). A complication during catheterization precluded embolization in another patient. Beginning as flow directed embolizations via carotid artery catheterizations (n = 12), newer catheters allowed progression to superselective intracerebral catheterizations (n = 38). Embolization has led to shorter surgical procedures, more clearly defined operative margins, and less bloody operative fields. We have not found recanalization to significantly hinder embolization results with polyvinyl alcohol when resection is undertaken within 1-4 weeks of embolization. Its relative safety and ease of manipulation at surgery argue for its use. We found no significant increase in complications based on patient age, venous drainage of the arteriovenous malformation, or the circulation embolized. Embolization results in cerebral arteriovenous malformations were improved with superselective catheterization and most improved with the combined use of polyvinyl alcohol for nidus embolization followed by occlusion of the feeding vessel with microcoils. PMID- 2112316 TI - Dural arteriovenous fistulas involving the inferior petrosal sinus: angiographic findings in six patients. AB - We report the angiographic findings from six patients with intracranial dural arteriovenous fistulas of the inferior petrosal sinus and describe the clinical presentation, vascular anatomy, and embolization techniques used in the treatment of this disorder. Dural arteriovenous fistulas at this site are rare; of 105 patients diagnosed with this abnormality, only six had lesions involving the inferior petrosal sinus. The patients included three men and three women, ranging in age from 41 to 75 years. Patients presented with bruit, proptosis, abducens palsy, or loss of vision, and symptoms were present for up to 1 year prior to diagnosis. These presentations were similar to cavernous sinus arteriovenous fistulas. The arterial supply in all cases was from branches of the external carotid artery and in three cases from the meningohypophyseal trunk of the internal carotid artery. Venous drainage in four patients was via the cavernous sinus to the superior ophthalmic vein. The remaining two patients had drainage primarily to the jugular bulb. In four patients treatment was performed by introducing wire coils into the fistula from the transvenous route. This approach could be used even though the inferior petrosal sinus was thrombosed. One patient, treated early in the series, had only transarterial embolization with both liquid adhesives and particulate embolic agents. One patient had an asymptomatic fistula that was not treated. All patients were cured, as evidenced both angiographically and clinically during the follow-up period. Three patients experienced complications from angiography and treatment: two had transverse sinus thrombosis and one had a transient ischemic attack. PMID- 2112317 TI - Unilateral double carotid cavernous fistula treated with detachable balloons. PMID- 2112318 TI - Arteriovenous fistulas of the cervicomedullary junction as a cause of myelopathy: radiographic findings in two cases. PMID- 2112319 TI - Aicardi syndrome: MR assessment of brain structure and myelination. PMID- 2112320 TI - Hemodynamic effects of Gd-DTPA administered via rapid bolus or slow infusion: a study in dogs. AB - The hemodynamic effects of rapid (10 sec) versus slow (1 min) IV injection of Gd DTPA were compared in normal, pentobarbital-anesthetized mongrel dogs. Hypertonic mannitol and isotonic saline were used as equiosmotic and equivolumetric controls. Two dose levels of Gd-DTPA were administered: 0.1 mmol/kg and 0.5 mmol/kg, corresponding to dose volumes of 0.2 and 1.0 ml/kg, respectively. The rapid injection of a high dose (0.5 mmol/kg) produced a transient decrease in arterial blood pressure (21 mm Hg, p less than .001), which returned to control values within 1 min after the injection. Slow IV infusion at this high dose had no statistically significant hemodynamic effects. There were no statistically significant effects of the lower dose (0.1 mmol/kg) administered as a bolus or by infusion, nor of the saline or osmotic control solutions. These results suggest that acute hemodynamic effects of Gd-DTPA are not observed at clinically relevant doses and the vasodilation observed at a higher dose may result from a direct action of the contrast agent. PMID- 2112321 TI - Facial skeleton remodeling due to temporomandibular joint degeneration: an imaging study of 100 patients. AB - One hundred patients with recently acquired, externally visible mandibular deformity and no history of previous extraarticular mandible fracture were selected for retrospective analysis. All had been investigated clinically and with radiography, tomography, and high-field surface-coil MR imaging to determine the presence or absence and extent of temporomandibular joint degeneration. Temporomandibular joint degeneration was found in either one or both joints of each patient studied. Chin deviation was always toward the smaller mandibular condyle or more diseased joint, and many patients either complained of or exhibited malocclusion, often manifested by unstable or fluctuating occlusion disturbances. Three radiologically distinct forms of degenerative vs adaptive osteocartilaginous processes--(1) osteoarthritis, (2) avascular necrosis, and (3) regressive remodeling--involving the mandibular condyle and temporal bone were identified in joints most often exhibiting meniscus derangement. Osteoarthritis and avascular necrosis of the mandibular condyle and temporal bone were generally associated with pain, mechanical joint symptoms, and occlusion disturbances. Regressive remodeling was less frequently associated with occlusion disturbances, despite remodeling of the facial skeleton, and appears to result from regional osteoporosis. Forty patients (52 joints) underwent open arthroplasty procedures, including either meniscectomy or microsurgical meniscus repair, at which time major radiologic diagnoses were confirmed. Surgical and pathologic findings included meniscus displacement, disk degeneration, synovitis, joint effusion, articular cartilage erosion, cartilage healing/fibrosis, cartilage hypertrophy, osseous sclerosis, osteophyte formation, osteochondritis dissecans, localized or extensive avascular necrosis, and decreased mandibular condyle mass and vertical dimension. We conclude that temporomandibular joint degeneration is the principal cause of both acquired facial skeleton remodeling and unstable occlusion in patients with intact dentition and without previous mandible fracture. PMID- 2112322 TI - CT demonstration of pneumatization of the uncinate process. PMID- 2112323 TI - Optic chiasm position on MR images. AB - This article describes the results of a study of the distance from the optic chiasm to the tuberculum sellae as seen on sagittal MR images. Measurements revealed an average chiasm-tuberculum distance of 3.8 mm (2.6 mm for females, 4.3 mm for males) and a sizable group in whom the distance was effectively zero. These results show a fairly close correlation with previous anatomic studies. The closer the chiasm is to the tuberculum, the earlier one may expect clinical manifestations of pituitary disease and the more difficult an intracranial surgical approach to the pituitary will be. PMID- 2112324 TI - Colloid cysts of the third ventricle: correlation of MR and CT findings with histology and chemical analysis. AB - Eight patients with colloid cysts of the third ventricle were examined with CT and MR. In six, surgical resection was performed and the material was subjected to histologic evaluation; the concentrations of trace elements were determined by particle-induced X-ray emission. Stereotaxic aspiration was performed in two. The investigation showed that colloid cysts are often iso- or hypodense relative to brain on CT (5/8), but sometimes have a center of increased density. Increased density did not correlate with increased concentration of calcium or other metals but did not correlate with high cholesterol content. Colloid cysts appear more heterogeneous on MR (6/8) than on CT (3/8), despite a homogeneous appearance at histology. High signal on short TR/TE sequences is correlated with a high cholesterol content. A marked shortening of the T2 relaxation time is often noticed in the central part of the cyst. Analysis of trace elements showed that this phenomenon is not related to the presence of metals with paramagnetic effects. Our analysis of the contents of colloid cysts does not support the theory that differing metallic concentrations are responsible for differences in MR signal intensity or CT density. We did find that increased CT density and high MR signal correlated with high cholesterol content. PMID- 2112325 TI - Recurrent medulloblastoma: frequency of tumor enhancement on Gd-DTPA MR imaging. AB - Thirty-two children with medulloblastoma were evaluated postoperatively with conventional and gadolinium-enhanced MR imaging. Eleven patients had abnormal cranial MR studies; nine of these had recurrent tumor. In six patients recurrent tumor enhanced with Gd, while in the other three patients recurrent tumor did not enhance. The remaining two patients had areas of abnormal Gd enhancement that were caused by radiation-induced breakdown of the blood-brain barrier rather than by recurrent tumor. This study shows that not all recurrent medulloblastoma enhances and that the absence of Gd enhancement does not necessarily indicate the absence of recurrent tumor. PMID- 2112326 TI - Fast multiphase MR imaging of aqueductal CSF flow: 1. Study of healthy subjects. AB - Gradient-echo MR sequences are more sensitive to flow phenomena than spin-echo sequences are. We investigated aqueductal CSF flow by fast multiphase imaging. Fast multiphase imaging offers the opportunity to perform a dynamic study of fluid motion that is synchronous with the cardiac cycle. A section perpendicular to the cerebral aqueduct was imaged in 18 healthy volunteers. Serial, gated (every 50 msec from the ECG R wave), flow-compensated modulus images with 70 degrees-flip-angle excitation pulses were obtained with a single acquisition. The behavior vs time of CSF signal in the aqueduct was compared with that in the lateral ventricles. The former showed a peak at 0.47 +/- 0.1 fractions of a heart cycle after the R wave. No periodicity with the heart rate was observed for the ventricular CSF signal intensity. The mean CSF signal intensity in the aqueduct was found to range from about twice to three times that in the lateral ventricles over a cardiac cycle. Fast multiphase imaging is a sensitive and practical sequence for the MR investigation of aqueductal CSF flow. Its potential in patients with hydrocephalus is studied in a companion article. PMID- 2112327 TI - Fast multiphase MR imaging of aqueductal CSF flow: 2. Study in patients with hydrocephalus. AB - The signal intensity in the region corresponding to the cerebral aqueduct was evaluated in three patients with noncommunicating tension hydrocephalus (caused by aqueductal obstruction in two and type I Arnold-Chiari malformation in the other), seven patients with suspected normal-pressure hydrocephalus (three of whom subsequently underwent successful shunting), and 10 patients with ex vacuo (atrophic) hydrocephalus. A gradient-echo MR sequence, called fast multiphase imaging, was used. Serial images corresponding to different phases of the cardiac cycle were acquired. No flow-related enhancement was observed over the entire cardiac cycle in the patients with noncommunicating hydrocephalus. Patients with normal-pressure hydrocephalus showed a higher aqueductal CSF signal intensity, consistent with increased systolic flow rates, than patients with ex vacuo hydrocephalus. When comparing the above two groups of patients with a control group of healthy volunteers, significantly higher and lower values of the (mean) maximum aqueductal signal intensity were found in the normal-pressure hydrocephalus patients and the ex vacuo hydrocephalus patients, respectively. Fast multiphase MR evaluation of aqueductal CSF flow may help to differentiate patients with different types of hydrocephalus. PMID- 2112328 TI - The laterally tilted dens: a sign of subtle odontoid fracture on plain radiography. AB - Type III (low) odontoid fractures may be subtle on initial plain film radiographic examination. We describe a sign on the routine open-mouth view, the laterally tilted dens, which has not been previously stressed in the radiologic literature, and is an important diagnostic sign of type III fractures of the odontoid process of the axis. In a series of 82 nontraumatized patients, no odontoid angle of less than 87 degrees (3 degrees from perpendicular) was observed. In a series of type III odontoid fractures, tilting of the dens in excess of 5 degrees was present in eight (67%) of 12 cases. This may be the only readily apparent finding on the initial cervical spine series. Of eight type III odontoid fractures in which an abnormal odontoid angle was identified, it was the only definite abnormality that could be recognized prospectively in two cases (25%) and that supported very subtle findings in two other cases (25%). PMID- 2112329 TI - Trigeminal sensory neuropathy caused by cervical disk herniation. PMID- 2112330 TI - Posterior spinal tuberculosis: a case report. PMID- 2112331 TI - Intradural paraganglioma of the thoracic spine. PMID- 2112332 TI - Meningeal fibrosis appearing shortly after ventricular shunting. PMID- 2112333 TI - Bupropion: new therapy for depression. AB - Bupropion is one of the most recently approved antidepressant drugs. The drug differs in chemical structure from the tricyclic antidepressants. It mechanism of action is unknown. Bupropion weakly blocks dopamine uptake, but this property does not seem to account for the antidepressant effects. In clinical trials, bupropion has shown satisfactory antidepressant action compared with placebo. Because long-term effects are not well established, bupropion should be discontinued after several months of therapy. PMID- 2112334 TI - A symposium: Advances in nitrate therapy (Part 2). Montreux, Switzerland. PMID- 2112335 TI - Nitrate therapy in the elderly. AB - Changes in the heart and blood vessels with age alter the response of the cardiovascular system to pharmacologic agents. Nitrate plasma half-life is longer and volume of distribution is larger in older persons. Apparently, these pharmacokinetic differences in older persons lead to increased venous smooth muscle responsivity to nitrates which, in turn, leads to greater reductions in central venous and pulmonary arterial pressures after nitrate administration. This is probably the explanation for the greater frequency of nitrate-induced severe hypotension and bradycardia in elderly patients with myocardial infarction compared with younger patients. Clinicians should be cognizant of the changes in the cardiovascular system which occur with age that sensitize the elderly patient to the action of organic nitrates. Initial dosages of nitrates should accordingly be less than in younger patients. PMID- 2112336 TI - Nitrate tolerance in heart failure: differential venous, pulmonary and systemic arterial effects. AB - The hemodynamic profile of tolerance to intravenous nitroglycerin was studied in 9 patients with New York Heart Association Class III to IV congestive heart failure. After rapid dosage build-up to the maximal tolerated dose (decrease in pulmonary wedge pressure to 10 mm Hg or systolic blood pressure to 90 mm Hg), nitroglycerin (525 +/- 548 micrograms/min) was administered at a constant continuous intravenous infusion for a total of 24 hours. The extent of nitrate tolerance at 24 hours was calculated as the percentage loss of the benefit achieved at time of peak effect of nitroglycerin. Tolerance had a different time course and magnitude in the venous, arterial and pulmonary circulations. At 24 hours, right atrial pressure and pulmonary vascular resistance returned to control values in most patients, while 40 to 50% of the effect on systemic vascular resistance, cardiac index and pulmonary wedge pressure was maintained. These findings emphasize the importance of precise definitions in studies relating to nitrate tolerance. PMID- 2112337 TI - Comparative evaluation of a new formulation of isosorbide dinitrate oral spray and sublingual nitroglycerin tablets. AB - The magnitude and time course of the hemodynamic effect of a new formulation of an aqueous solution of isosorbide dinitrate (ISDN) spray were compared with those of sublingual nitroglycerin (NTG) tablets in 12 patients with chronic congestive heart failure. The patients received, in a random order, ISDN spray, 2.5 mg, or sublingual NTG, 0.8 mg. Hemodynamic measurements were performed before and at 1, 3, 5, 10, 20, 30 and 60 minutes after each drug. The second drug was given only after return of the hemodynamic parameters to baseline, plus a washout period of 2 hours. The hemodynamic variables measured were comparable at baseline. Both drugs produced hemodynamic improvement including a decrease in pulmonary capillary wedge pressure (PCWP), right atrial pressure and systemic and pulmonary vascular resistances. Only ISDN spray significantly increased cardiac output. The onset of action of ISDN spray was significantly more rapid than that of NTG. This was primarily evident in the decrease in PCWP. With ISDN spray the decrease started at 1 minute after administration, and at 3 minutes a decrease of 8.6 mm Hg was already found. The corresponding value for sublingual NTG was 1.6 mm Hg. The difference was highly significant (p less than 0.02). The peak effect of ISDN spray on PCWP and right atrial pressure was greater than that of NTG. Thus, the onset of the hemodynamic effect of the new formulation of ISDN spray is much more rapid than that of sublingual NTG tablets. At the doses used, the magnitude of the effect of the ISDN spray on some of the hemodynamic variables is greater than that of sublingual NTG. PMID- 2112338 TI - Long-term efficacy of nitroglycerin patch in stable angina pectoris. AB - Subchronic and chronic efficacy of a 10 mg of nitroglycerin (NTG) patch was studied in 30 patients with stable angina pectoris. The trial consisted of 2 periods of study: 1 period of 2 months with a double-blind, crossover, placebo controlled design and a second period of open treatment with verum patch. Two 7 day washout periods were performed at entry and at the end of the study. Efficacy was evaluated by clinical assessment of anginal attacks and NTG consumption and by means of multistage treadmill exercise testing. Exercise tests were performed at time 0 (24 hours from application of last patch), at 4 and 12 hours after dosing at the end of first 7-day washout, at the end of the first month of treatment, at the end of the second month of treatment after crossover, at the end of 3 months of treatment with active patch and at the end of the second 7-day washout period. Statistics were obtained by multivariate analysis of difference. In 27 patients whose records were available for final analysis the daily attacks of angina and NTG consumption decreased significantly during both the subchronic and chronic phases of the trial compared with placebo (p less than 0.001). Subchronic study showed significant improvement of maximal exercise duration, time to onset of angina, time to ST-segment depression of 1.0 mm, time to regression of angina and time to regression of ST depression, compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112339 TI - Very early nutrition supplementation in burned patients. AB - We studied some metabolic and hormonal effects of a very early nutrition supplementation in burned patients. The patients were divided into two groups of 10 patients each. Supplementation in the first group, the very early nutritionally supplemented (VENS) group, was started immediately after admission, ie, after 4.4 +/- 0.5 h (mean +/- SEM) from the injury; it was started after 57.7 +/- 2.6 h from the injury in the second group (control group). Hormonal and metabolic indices were recorded every 4 d up to 28 d. In the VENS group, the nitrogen balance became positive in 8.8 +/- 4.1 d whereas it took 24.1 +/- 6.9 d in the control group (p less than 0.05). Urinary catecholamine excretion and plasma glucagon concentrations were lower during the first 2 wk of observation in the VENS group compared with the control group. Insulin concentrations were significantly higher on the fourth and eighth days in VENS patients and plasma cortisol concentrations were similar in both groups. PMID- 2112340 TI - Estimating resting energy expenditure by simple lean-body-mass indicators in children on total parenteral nutrition. AB - The aim of this study was to determine simple predictive factors of the resting energy expenditure (REE) in children. Two groups, A (n = 14) and B (n = 23), were defined by their weight-for-height index, less than 90% and greater than 90%, respectively. Anthropometrically assessed lean body mass (LBM), 24-h urinary creatinine, and REE were measured. From multiple-regression analysis, the best fitting equation for calculating REE (REE = 54.4 LBM (kg) + 0.095 creatinine (mmol/kg) + 4.7) was highly significant (r = 0.987, p less than 0.0001). Although the regressions of REE on weight were significantly different between the two groups, the equations using LBM or 24-h urinary creatinine did not discriminate between them. These findings suggest that an equation based on LBM or 24-h urinary creatinine excretion could be a more accurate estimate of REE than are conventional methods based on weight or height, and it may be applicable to diverse nutritional states. PMID- 2112341 TI - Extensive genetic heterogeneity in patients with acid alpha glucosidase deficiency as detected by abnormalities of DNA and mRNA. AB - Acid maltase, or acid alpha glucosidase (GAA), is a lysosomal enzyme that hydrolyzes glycogen to glucose and is deficient in glycogen storage disease type II. We have previously isolated a partial cDNA (1.9 kb) for human GAA and detected abnormalities of mRNA in two infantile-onset and one adult-onset patient. We have now extended this study and examined mRNA and DNA from cell lines of eight additional infantile and three adult-onset patients. While five of the 10 infantile-onset patients expressed normal amounts and sizes of mRNA, the remaining five did not express detectable GAA mRNA. Two adult-onset patients had normal amounts and sizes of mRNA, while two adult-onset patients had mRNA of smaller size. Thus, half of the larger series of GAA-deficient patients also exhibited quantitative and/or qualitative abnormalities of mRNA. Of the five infantile-onset patients with normal mRNA, two exhibited an abnormal SacI fragment not found in DNA from 60 normals. To further characterize these patients, we determined GAA activity in several of the cell lines by using either the artificial substrate, 4-methylumbelliferyl-alpha-D-glucoside, or the natural substrate glycogen. Two adult-onset patients who both had normal size mRNA differed as to enzyme activity, with one patient exhibiting enzyme activity similar to that in infantile-onset patients. By combining these data with those for previously reported presence or absence of GAA-mutant protein cross-reacting to antibody, we provide evidence for a minimum of six different mutations in these 14 GAA-deficient cell lines. PMID- 2112342 TI - Evaluation of apolipoprotein A-I containing particles in chronic renal failure patients undergoing hemodialysis. PMID- 2112343 TI - Risks, options, and informed consent for blood transfusion in elective surgery. AB - Blood banking is undergoing a period of significant change as a result of several concurrent issues. Blood-transmitted diseases such as human immunodeficiency virus (HIV) and the alternatives to community-derived (homologous) blood such as autologous (patient's own) and designated (blood donor known to transfusion recipient) blood have had an impact on surgical transfusion practice. Many of these issues comprise the medicolegal elements of informed consent for elective blood transfusion, so that increasingly the need for a dialogue incorporating these issues between the transfusing physician and the potential transfusion recipient is recognized. If the process is to be effective, then early involvement of the patient in a dialogue concerning informed consent is necessary. An overview of the medical elements and content of informed consent for elective blood transfusion is presented. PMID- 2112344 TI - Acute alcohol infusion does not alter plasma gonadotropins or prolactin in ovariectomized rats. AB - We examined the effects of acute alcohol on basal plasma FSH, LH, and prolactin in ovariectomized rats. Alcohol infusion and blood sampling were done via an indwelling atrial catheter. Blood samples for alcohol and hormone determinations were collected before, and 5 to 120 min after completion of saline (control) or alcohol in saline (experimental) infusion. Plasma follicle-stimulating hormone, luteinizing hormone, and prolactin were not altered during the 2-hr period. Peak blood alcohol concentrations achieved following 1.0- and 2.0-g/kg body weight of alcohol doses were approximately equal to, and twice, the legal human intoxication levels, respectively. Alcohol clearance rates from blood for the two groups were: 130 +/- 3 mg/kg/hr for the 1.0-g/kg body weight group and 151 +/- 3 mg/kg/hr for the 2.0-g/kg body weight group. These results show that acute alcohol does not affect basal gonadotropins and prolactin secretion in ovariectomized rats. PMID- 2112345 TI - Measurement of cerebral blood flow and volume with positron emission tomography during isoflurane administration in the hypocapnic baboon. AB - Using positron emission tomography, cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured after the addition of isoflurane (1.3 vols %, end tidal concentration) to neuroleptanesthesia (fentanyl/droperidol) in hypocapnic baboons. The study was designed to determine whether isoflurane, when administered during hypocapnia, acted as a cerebral vasodilator to increase either CBF or CBV. Mean arterial pressure was maintained within 10% of preisoflurane levels with an angiotensin infusion. In the first protocol (A), CBF and CBV were measured as close together in time as possible in order to detect divergent effects of isoflurane on these variables. When PaCO2 was reduced from 40 mmHg to 25 mmHg, CBF decreased from 44 +/- 4 to 31 +/- 4 ml.100 g-1.min-1 (P less than 0.05) and CBV decreased from 3.1 +/- 0.3 to 2.6 +/- 0.3 ml/100 g (P less than .05). Neither CBF nor CBV was significantly changed by the addition of isoflurane. In the second protocol (B), serial CBV scans were performed frequently during the addition of isoflurane in a fashion designed to detect transient changes in CBV at the time isoflurane was first added to the breathing circuit. Induction of hypocapnia again reduced CBV from 3.1 +/- .3 to 2.7 +/- .2 ml/100 g, (P less than .05) and addition of isoflurane did not change CBV. From these results the authors conclude that in the normal hypocapnic baboon the addition of 1.3% isoflurane does not significantly change cerebral blood flow or volume. PMID- 2112346 TI - A comparison of washed red blood cells versus packed red blood cells (AS-1) for cardiopulmonary bypass prime and their effects on blood glucose concentration in children. AB - The effects on blood glucose concentrations of packed red blood cells (AS-1) (group I) versus washed red blood cells (group II) for cardiopulmonary bypass prime were compared in 20 infants weighing less than 10 kg undergoing cardiac surgical procedures. All patients were anesthetized with N2O/O2/isoflurane/fentanyl and received lactated Ringer's solution prior to bypass. Blood glucose concentrations prior to bypass were 85 +/- 15 mg/dl (mean +/- SD) in group I and 81 +/- 14 mg/dl in group II. Blood glucose concentrations were 210 +/- 21 mg/dl versus 78 +/- 14 mg/dl (P less than 0.001) 10 min after initiation of bypass, 241 +/- 48 mg/dl versus 107 +/- 28 mg/dl (P less than 0.001) prior to separation from bypass, and 214 +/- 52 mg/dl versus 97 +/- 19 mg/dl (P less than 0.001) after protamine administration in group I and group II, respectively. The use of washed red blood cells for cardiopulmonary bypass priming solution in infants significantly attenuates the increase in blood glucose concentration otherwise observed during cardiopulmonary bypass. PMID- 2112347 TI - [The use of artificial feeding during the resuscitation of heart surgery patients]. AB - The data on the use of various schemes of artificial nutrition (AN) are reviewed in 137 patients with postoperative complications after cardiopulmonary bypass surgery. It has been established that AN as part of a complex therapy of patients in the early postoperative period has a correcting effect on metabolism and promotes the improvement of the patients' clinical condition. Rational combination of parenteral and enteral tube nutrition ensures adequate AN of cardiosurgical patients in the early postoperative period. PMID- 2112348 TI - Vasomotion influences airflow in peripheral airways. AB - The purpose of this study was to test the hypothesis that blood flow, by its effect on blood volume, influences airflow resistance in peripheral airways. In conscious ewes, forced sinusoidal flow oscillations (5 Hz) were applied through a balloon-tipped, dual-channel fiberoptic bronchoscope placed in a segmental bronchus, and peripheral airflow resistance (Rp) was determined from flow and bronchial pressure. Drugs with predominant vascular or airway smooth muscle effects were administered locally through the bronchoscope. Nitroglycerin (NTG) produced a dose-dependent increase in mean Rp (+288% at 1,000 micrograms), which was blocked by methylene blue (p less than 0.05) and not reversed by atropine. Carbachol (CARB) also increased mean Rp in a dose-dependent manner (+605% at 400 micrograms); this effect was not blocked by methylene blue, but it was reversed by atropine (p less than 0.05). The increase in mean Rp after a single dose of NTG (250 micrograms) was sustained for at least 20 min and transiently reversed by vasopressin (0.2 units, p less than 0.05) but not by isoproterenol (100 micrograms). Conversely, the sustained increase in Rp after a single dose of CARB (50 micrograms) was transiently reversed by isoproterenol (p less than 0.05) but not by vasopressin. We conclude that NTG increased Rp by vasodilation and CARB by bronchoconstriction. This supports the hypothesis that vasodilation limits airflow in the lung periphery, presumably because of vascular congestion. PMID- 2112349 TI - Studies on the relationships between sensitivity to cold, dry air, hyperosmolal solutions, and histamine in the adult nose. AB - We have previously reported that elevated osmolality of nasal secretions is linked to the rhinitic reaction to cold and dry air (CDA) that results in inflammatory mediator release and that nasal challenge with hyperosmolal solutions can induce histamine release in randomly selected individuals. These findings led to a comparison of the effect of nasal challenge with hypertonic fluid in 11 subjects who demonstrated a nasal response to CDA compared to 10 subjects without CDA sensitivity. All volunteers were challenged with isosmolal (300 mosmol/kg H2O) and hyperosmolal (800 mosmol/kg H2O) mannitol solutions. Their response was evaluated by symptom scores and quantification of histamine in nasal lavages. CDA responders differed significantly from non-responders in terms of both the total amount and the concentration of histamine in the lavage following hyperosmolal challenge (p less than 0.04 and p less than 0.02, respectively). In addition, CDA responders reported a higher change from baseline for nasal congestion, pruritus, and lacrimation following hyperosmolal challenge, but the scores for rhinorrhea, the volume of the returned nasal lavage fluid following hyperosmolal challenge, and the capacity to reduce the osmolality of the administered hyperosmolal fluid did not differ. Allergic status was not a factor in hyperosmolal reactivity. To investigate possible differences in nonspecific nasal mucosal sensitivity that could account for these findings, all subjects underwent provocation with five increasing doses of histamine, from 0.01 to 1 mg. No significant difference between CDA responders and nonresponders in symptomatology or in the induction of vascular permeability, as assessed by TAME esterase activity in nasal fluids, could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112350 TI - The effects of exposure time, drug concentration, and temperature on the activity of ethambutol versus Mycobacterium tuberculosis. AB - In a series of dynamic in vitro studies designed to assess the activity of ethambutol (EMB) against Mycobacterium tuberculosis, we made the following observations. Ethambutol showed bactericidal action with 10 micrograms/ml concentration when in constant contact with M. tuberculosis. At a lower concentration, bactericidal action was evident up to 6 days; after that time, this effect was lost owing to the development of drug-resistant mutants. The bactericidal action of ethambutol in this model was similar to that of rifampin and isoniazid. Pulsed exposure for 96 h caused a four-log reduction in cfu counts, but the growth resumed rapidly. The bactericidal action of ethambutol was maximal at 37 degrees C and less at low temperatures. Ethambutol showed little activity against cultures growing at 8 degrees C continuously that were incubated for only 1 h at 37 degrees C. Against cultures growing at 8 degrees C that were brought to 37 degrees C for 6 h, its action was similar to that of rifampin. Ethambutol combined with other drugs showed bactericidal action, although the activity was less than that of the combination isoniazid-streptomycin. PMID- 2112351 TI - Significance of false-positive serologic tests for histoplasmosis and blastomycosis in an endemic area. AB - False-positive serologic tests for histoplasmosis (H) and blastomycosis (B) are common in populations from endemic areas. In order to determine the significance of false-positive test results, we reviewed the final diagnoses of all patients whose sera were submitted to our laboratory for radioimmunoassay (RIA) and immunodiffusion (ID) during a 3-yr period. Of the 263 patients whose sera were examined, 29 (11%) had H or B; 41 (17.5%) of the remaining 234 patients had false positive test results. Of these 41 patients, 31 were positive for H alone, and 10 had antibodies to both H and B. All three patients with false-positive ID tests for histoplasmosis also had positive titers (greater than or equal to 1:16) on RIA. No patient had a false-positive ID result for blastomycosis. The percentage of patients in each of five major diagnostic categories with and without false positive serologic tests was similar (p greater than 0.05). The majority of patients had pulmonary infections, almost half of which were granulomatous infections other than H or B; this reflects the clinical indications for requesting fungal serologic tests. A positive fungal serology is not useful in suggesting the presence of a pulmonary disease other than H or B in patients from an endemic area suspected of having a pulmonary mycosis. PMID- 2112352 TI - Low risk for hepatitis C in hemophiliacs given a high-purity, pasteurized factor VIII concentrate. International Study Group. AB - STUDY OBJECTIVE: To assess whether the hepatitis B virus (HBV), the hepatitis C virus (HCV), and the human immunodeficiency virus (HIV) are transmitted to hemophiliacs by a high-purity factor VIII concentrate in which the method of virus inactivation is pasteurization. DESIGN: Hepatitis B virus markers, the antibody to HCV (anti-HCV), the antibody to HIV (anti-HIV), and aminotransferases were measured on serum samples collected before the first concentrate infusion and at regular time intervals thereafter. SETTING: Seventeen hemophilia centers in Italy, the Federal Republic of Germany, Belgium, Austria, and the Democratic Republic of Germany. PATIENTS: Twenty-nine patients with hemophilia A who had not received a previous transfusion with blood products and who had normal alanine and aspartate aminotransferases (ALT and AST) were included in the final analysis. MEASUREMENTS AND MAIN RESULTS: No patient became positive for anti-HCV or anti-HIV or developed sustained increases in aminotransferase levels. Similarly, none of the 15 unvaccinated patients developed markers of HBV infection. CONCLUSION: This prospective study conducted in previously untransfused hemophiliacs highly susceptible to developing post-transfusion hepatitis shows that a large-pool clotting factor concentrate treated with pasteurization carries a low risk for transmitting HCV, the major causative agent of post-transfusion hepatitis. PMID- 2112353 TI - NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis). An update. AB - The neurofibromatoses comprise at least two autosomal dominant disorders affecting an estimated 100,000 Americans with clinical manifestations that may require care from every type of clinician. Neurofibromatosis 1 and neurofibromatosis 2 have in common the occurrence of many neurofibromas but are distinctly different clinical disorders. The disease genes are on different chromosomes. Magnetic resonance imaging, particularly with gadolinium enhancement, has generally supplanted other techniques for visualizing brain, spinal, and other neural tumors in both disorders. The technique has rekindled the controversy over the nature and frequency of optic pathway tumors in patients with neurofibromatosis 1 and has revealed, throughout the brains of young patients, bright lesions that have uncertain clinical consequences and unknown pathologic bases. In patients with neurofibromatosis 2, small acoustic neuromas can be seen, leading to the possibility of excision with preservation of hearing and facial nerve function. Abnormal hearing may occur to excess in patients with neurofibromatosis 1, but acoustic neuroma has never been documented. In patients with neurofibromatosis 2, a battery of audiologic tests has a high positive predictive power. Lisch nodules or iris hamartomas, probably a universal sign in adults with the neurofibromatosis 1 gene, cause no problem with vision. Posterior capsular lens opacity in patients with neurofibromatosis 2 is a helpful diagnostic sign and a potential source of additional handicap in persons at risk for impaired hearing. Progress in the clinical delineation of the disorders has been matched with considerable research into the still obscure pathogenesis of the disorders. Such rapid advances may necessitate reconsideration of the conclusions of the National Institutes of Health Consensus Development Conference on Neurofibromatosis, especially those on the categories of persons in which a neurofibromatosis should be considered and the need for caution in recommending surgery. Watchful waiting may often be the best management for acoustic neuromas in neurofibromatosis 2. PMID- 2112354 TI - The lupus anticoagulant and retinal vaso-occlusive disease. AB - A patient with a history of hypertension had a combined central retinal artery and vein occlusion in one eye. She had markedly elevated coagulation profiles, especially the partial thromboplastin time, secondary to circulating lupus anticoagulant. Due to the asymmetric involvement, the presence of the anticoagulant, and the lack of any other signs of retinopathy, we believed that the etiology was thrombotic rather than vasculitic. Detection and measurement of the lupus anticoagulant could serve as a marker of disease and in the assessment of disease activity in the follow-up of these patients. PMID- 2112355 TI - Effect of arachidonic acid on the inner ear blood flow measured with a laser Doppler flowmeter. AB - The present study was undertaken to clarify the effect of arachidonic acid (AA) on the inner ear blood flow of rats as measured with a laser Doppler flowmeter. With the rats under anesthesia with sodium pentobarbital, the middle ear was approached ventrally and a laser Doppler probe was positioned over the lateral wall of the cochlea. Drugs were administered via the subclavicular artery. The dose range of each drug was determined so as not to affect the systemic blood pressure. The AA (20 to 70 micrograms) increased the inner ear blood flow dose dependently; this effect was abolished by indomethacin (5 mg orally). Both prostaglandin E2 (PGE2; 1 to 50 ng) and CS-570, a PGI2 analogue (12.8 to 25.6 ng) caused a dose-dependent increase in the inner ear blood flow. The response of PGI2 was shorter than that of PGE2. On the other hand, a stable thromboxane A2 (STA2; 30 to 80 ng) decreased the inner ear blood flow dose-dependently. Administration of PGF2 alpha (0.2 to 3 micrograms) showed no effect on the inner ear blood flow. These results indicated that the effect of AA was mediated mainly via PGI2 and PGE2. PMID- 2112356 TI - Ossified auricle in Addison's disease. PMID- 2112357 TI - Otitis media research: the NIH perspective. PMID- 2112358 TI - Otopathologic correlates of the continuum of otitis media. AB - It has been our hypothesis that different types of middle ear effusions and the clinical manifestations with which they are associated represent the typical inflammatory response. Employing an animal model under controlled conditions, we present statistical evidence that change in the mucosa of the middle ear in otitis media can occur along a continuum, with early forms regressing to more chronic stages of the disease. We also demonstrate an increase in the thickness and a decrease in the permeability of the round window membrane in a longitudinal study of otitis media in the same animal model. Histopathologic changes in human temporal bones with otitis media with effusion or chronic otitis media are similar to the changes in the animal models. These results support a concept that all categories of otitis media (serous, purulent, mucoid, and chronic) represent different stages in a continuum of events. PMID- 2112359 TI - Morphometric studies of the continuum of otitis media. AB - Morphometric changes in the epithelium and subepithelium of the middle ear mucosa from children younger than 10 years of age were measured at the promontory in 85 temporal bones with otitis media and in 29 normal temporal bones by use of quantitative and semiquantitative methods. Comparisons of morphologic analysis in different otitis media types showed that acute inflammatory changes were usually seen in purulent otitis media with effusion and serous otitis media with effusion, and chronic inflammatory changes were more severe in mucoid otitis media with effusion and chronic otitis media. There were overlaps, however, in histopathologic findings between different types of otitis media that suggest a continuum of otitis media types, with one type of otitis media changing into another type. PMID- 2112360 TI - Role of middle ear endotoxin in inner ear inflammatory response and hydrops: long term study. AB - The permeability of the round window membrane for Salmonella typhimurium-derived endotoxin was examined with use of a total of 33 chinchillas. One milligram of each endotoxin was instilled into the tympanic cavities via the superior bullae. The endotoxin activities in middle ear effusions (MEEs), perilymph, and sera were determined by limulus amebocyte lysate assay. Endotoxin was detected in perilymph on the inoculated side by 12 hours after endotoxin instillation and persisted for up to 3 weeks. Endotoxin level peaked at 24 to 48 hours postinstillation, and it steadily declined afterward. This result suggests that the maximum penetration occurred during the active inflammatory stage. Histologic evidence demonstrated remarkable pathologic changes in the inner ear, including bleeding and inflammatory cell recruitment, mostly in the perilymphatic spaces (eg, scalae tympani, scalae vestibuli, spiral ligament), strial swelling, and sensory cell degeneration. This result suggests that endotoxin present in the middle ear can permeate the round window membrane, causing inner ear tissue damage in this animal model. PMID- 2112361 TI - Outer hair cells as potential targets of inflammatory mediators. AB - Inner ear sequelae with temporary or permanent sensorineural hearing loss can result from inflammatory processes in the middle ear. Loss of outer hair cells in the base of the cochlea has been noted in otitis media, but it is not known how this damage occurs. Evidence supports the permeability of the round window membrane to substances mediating inflammation in the middle ear, and the presence of white blood cells has been reported in the perilymph. In the present study, the potential cytotoxic effects of two representative inflammatory mediators, endotoxin and free radicals, have been evaluated by use of short-term culture of isolated outer hair cells from the guinea pig cochlea model. Incubation with endotoxins from two gram-negative pathogens increased the rate of hair cell death fourfold to sixfold. Free radicals (generated by exposure of cells to UV light or by excitation of intracellular fluorescent dyes) produced morphologic damage to hair cells within 60 seconds. These latter effects were delayed by addition of free-radical scavengers. It is concluded that inflammatory mediators are cytotoxic to hair cells and therefore are potentially ototoxic if permeating the round window membrane. PMID- 2112362 TI - Clinical perspectives on ototoxic drugs. AB - Ototoxic drugs such as salicylates, the aminoglycoside antibiotics, loop diuretics, cisplatin, erythromycin, and vancomycin are widely used in clinical practice. The most commonly used are aspirin and the aminoglycoside antibiotics. This chapter briefly discusses the pharmacology of the commonly prescribed ototoxic drugs and the doses that may result in ototoxicity. An outline for the monitoring of ototoxic drugs is presented. The role of topical ear drops as a possible cause of ototoxicity is reviewed. PMID- 2112363 TI - Toxicity of ototopical drugs: animal modeling. AB - It is important to be aware of the potential ototoxicity of any drug, vehicle, or antiseptic that is used in the middle ear. Frequently used ear drops (Cortisporin otic suspension, Coly-Mycin S Otic, and VoSoL otic solution) were studied for their ototoxicity. Compound action potentials were measured before and at 1, 2, and 24 hours following drug application on the round window membranes of chinchillas. Each drug was applied for 10 minutes and then was removed by rinsing. The sound pressure in decibels sound pressure level that produced a compound action potential amplitude of 10 microV was defined as the threshold. The change in threshold was interpreted as hearing loss. On the basis of the short-term results at 24 hours following drug application, the ototoxicity of Coly-Mycin was calculated to be twice that of Cortisporin, and the ototoxicity of VoSoL four times that of Cortisporin. PMID- 2112364 TI - Historical perspectives and concepts in otitis media research at the University of Minnesota. AB - The University of Minnesota Otitis Media Research Center, formed in 1978, comprises a multidisciplinary research team in the clinical fields of otolaryngology, pediatrics, audiology, and infectious disease as well as the basic science fields of histopathology, epidemiology, microbiology, immunology, biostatistics, pharmacology, physiology, and biochemistry. The team has focused on studies designed to elucidate the pathophysiology of the otitis media continuum, and considerable progress has been made in describing this continuum by using the basic science approaches available in the Center. The collaboration of basic and clinical scientists has created a synergy of goals, ideas, and methods leading to new hypotheses and progress, ultimately resulting in improved patient care methods. PMID- 2112365 TI - Increasing flap survival: a new method. AB - A new method of continuous irrigation beneath a flap with special irrigation was designed to attempt to improve flap survival in 42 animals. In each animal experimental and control flaps were symmetrically designed using two flanks or limbs (total number of flaps, 154). The flap length survival in the 77 experimental flaps ranged from 18 to 88% greater than that in the control flaps. Bacterial cultures of the secretions from all flaps suggested that this method has a practical value in preventing and controlling the infections that would result in flap necrosis. PMID- 2112366 TI - Immobilization of amyloglucosidase using two forms of polyurethane polymer. AB - Amyloglucosidase was covalently immobilized using two hydrophilic prepolymers: Hypol FHP 2002 (creates foams) and Hypol FHP 8190H (creates gels). The foamable prepolymer was superior as a support for enzyme immobilization. The percent activity immobilized in the polyurethane foams was 25 +/- 1.5%. Large substrates (greater than 200,000 daltons in mol wt) were hydrolyzed as effectively as smaller ones by the immobilized enzyme. The Km value of the foam-immobilized enzyme increased from 0.76 mg/mL (free) to 0.86 mg/mL (immobilized), whereas the Vmax dropped from 90.9 (free) to 12.4 nmol glucose/min/mL (immobilized). The long term (2 mo) storage stability of amyloglucosidase was enhanced by immobilization in foams (70% activity retained; free enzyme only retained 50%). Immobilization also improved the enzyme stability to various denaturing agents (sodium chloride, urea, and ethanol). The immobilized enzyme exhibited increased stability compared to the free enzyme at high temperatures (95 degrees C). Both glycogen and starch could be utilized by the immobilized enzyme, indicating that this technique could prove useful for starch hydrolysis. PMID- 2112367 TI - Occurrence of 9- and 13-keto-octadecadienoic acid in biological membranes oxygenated by the reticulocyte lipoxygenase. AB - Membranes of intact rabbit reticulocytes and rat liver mitochondrial membranes oxygenated by the pure reticulocyte lipoxygenase contain 13-keto-9Z,11E octadecadienoic acid and 9-keto-10E,12Z-octadecadienoic acid. In mitochondrial membranes not treated with lipoxygenase and in rabbit erythrocyte membranes these products were not detected. The chemical structure of the compounds has been identified by cochromatography with authentic standards on various types of HPLC columns, by uv and ir spectroscopy and GC/MS. In the membranes of rabbit reticulocytes up to 2% of the linoleate residues are present as its 9- and 13 keto derivatives. Most of the keto compounds (up to 90%) are esterified in the membrane ester lipids, only about 10% were found in the free fatty acid fraction. It is proposed that the keto dienoic fatty acids are formed via decomposition of hydroperoxy polyenoic fatty acids originating from the oxygenation of the membrane lipids by the reticulocyte lipoxygenase. PMID- 2112368 TI - Regulation of poly(ADP-ribose) polymerase mRNA levels during compensatory and mitogen-induced growth of rat liver. AB - Poly(ADP-ribose) polymerase mRNA levels were studied in hepatic regeneration following partial hepatectomy, and in hyperplasia induced by the mitogen lead nitrate. A significant increase in the level of poly(ADP-ribose) polymerase mRNA was found 8 h after partial hepatectomy when no detectable increase of DNA synthesis could be observed; the level of poly(ADP-ribose) polymerase transcripts increased up to six-fold within 1-2 days. A similar increase of the level of poly(ADP-ribose) polymerase mRNA was found 24 h after treatment with lead nitrate. A twofold increase in poly(ADP-ribose) polymerase activity was observed 2 days after (a) partial hepatectomy and (b) lead nitrate treatment. From these results an important role of poly(ADP-ribose) polymerase in cell proliferation could be suggested. PMID- 2112369 TI - Properties of a novel nitric oxide-stimulated ADP-ribosyltransferase. AB - A novel ADP-ribosyltransferase is present in the cytosolic fraction of various cells. The kinetic behavior and physical properties of this enzyme's activity are clearly distinguished from other known cytosolic ADP-ribosyltransferases. Agents that release nitric oxide, such as sodium nitroprusside, greatly stimulated this activity, although this effect was dependent on the presence of intact thiol groups. Dithiothreitol, reduced glutathione, or cysteine was needed for activation of the enzyme, while N-ethylmaleimide inhibited enzyme activity. High concentrations of phosphate had a slight stimulatory effect, while high concentrations of sodium chloride and thiocyanate were inhibitory. ATP also inhibited this activity. This cytosolic ADP-ribosyltransferase is clearly distinguished from other known and characterized cytosolic transferases. Its activation by biologically active nitric oxide suggests an important role for this enzymatic activity. PMID- 2112370 TI - Sarcolemmal carbonic anhydrase in red and white rabbit skeletal muscle. AB - Sarcolemmal vesicles of white and red skeletal muscles of the rabbit were prepared by consecutive density gradient centrifugations in sucrose and dextran according to Seiler and Fleischer (1982, J. Biol. Chem. 257, 13,862-13,871). White and red muscle membrane fractions enriched in sarcolemma were characterized by high ouabain-sensitive Na+, K(+)-ATPase, by high Mg2(+)-ATPase activity, and by a high cholesterol content. Ca2(+)-ATPase activity, a marker enzyme for sarcoplasmic reticulum, was not detectable in the highly purified white and red muscle sarcolemmal fractions. White and red muscle sarcolemmal fractions exhibited no significant differences with regard to Na+, K(+)-ATPase, Mg2(+) ATPase, and cholesterol. Specific activity of carbonic anhydrase in white muscle sarcolemmal fractions was 38 U.ml/mg and was 17.6 U.ml/mg in red muscle sarcolemma. Inhibition properties of sarcolemmal carbonic anhydrase were analyzed for acetazolamide, chlorzolamide, and cyanate. White muscle sarcolemmal carbonic anhydrase is characterized by inhibition constants, KI, toward acetazolamide of 4.6 X 10(-8) M, toward chlorzolamide of 0.75 X 10(-8) M, and toward cyanate of 1.3 X 10(-4) M. Red muscle sarcolemmal carbonic anhydrase is characterized by KI values toward acetazolamide of 8.1 X 10(-8) M, toward chlorzolamide of 6.3 X 10( 8) M, and toward cyanate of 0.81 X 10(-4) M. In contrast to the high specific carbonic anhydrase activities in sarcolemma, carbonic anhydrase activity in sarcoplasmic reticulum from white muscle varied between values of only 0.7 and 3.3 U.ml/mg. Carbonic anhydrase of red muscle sarcoplasmic reticulum ranged from 2.4 to 3.7 U.ml/mg. PMID- 2112371 TI - [Experimental studies on the combined effect of radiation and UFT: 2. fractionated treatments combining UFT and X ray radiation]. AB - The combined effects of fractionated radiation and UFT, which is a mixture of tegafur (FT) and uracil, have been studied using C3H mouse mammary carcinoma. The tumor was implanted in the right hind legs of and irradiated with 300R daily for either 10 or 15 days. UFT (FT 15mg/kg + uracil 33.6mg/kg) was intra-gastrically administered 2 hr. before irradiation. Dose modifying factor (DMF) of UFT obtained from the tumor growth delay assay was 1.52 for 10 fractions (3,000R) and 1.27 for 15 fractions (4,500R). The continuous administrations of UFT for one month after combination treatment suppressed the tumor regrowth. It is suggested that UFT is a useful radiosensitizer for concurrent fractionated radiation and useful adjuvant agent after radiation therapy. PMID- 2112372 TI - [A comparative study of UFT enteric-coated granules with UFT capsules on the occurrence of side effects in patients with head and neck cancers--a special attention to the upper gastrointestinal tract disorders]. AB - A comparative study on the occurrence of gastrointestinal side effects between UFT enteric-coated granules (UE) and UFT capsules (UC) was made by crossover method in 50 patients with head and neck cancer who were treated by these drugs as a surgical and/or radiation adjuvant chemotherapy. UE was significantly low in the occurrence of upper gastrointestinal side effects; remarkably low in such side effects as nausea and vomiting, in particular. On the other hand, there was little difference between UE and UC in the occurrence of such side effects as diarrhea, stomatitis, dry mouth and hematotoxic signs. The present result suggests that UE is clinically useful for treating the patients with cancer, with less occurrence of gastrointestinal side effects. PMID- 2112373 TI - [Usage of urine FT levels for medication compliance in head and neck cancer with administration of UFT]. PMID- 2112374 TI - Specificity of serotonin reuptake inhibitors in the treatment of obsessive compulsive disorder. Comparison of fluvoxamine and desipramine. AB - To evaluate whether serotonin reuptake inhibition is critical to the treatment of obsessive-compulsive disorder, 40 outpatients with a principal diagnosis of obsessive-compulsive disorder were randomized in a double-blind fashion to 8 weeks of treatment with either the serotonin reuptake inhibitor fluvoxamine maleate (n = 21) or the norepinephrine reuptake inhibitor desipramine hydrochloride (n = 19). Fluvoxamine was significantly better than desipramine in reducing the severity of obsessive-compulsive symptoms, as measured by the Yale Brown Obsessive Compulsive Scale and by the global response rate ("responder" equaling "much improved"). Eleven of 21 patients were responders with fluvoxamine compared with 2 of 19 patients with desipramine. Fluvoxamine, but not desipramine, was also effective in reducing the severity of "secondary" depression. Fluvoxamine-induced improvement in symptoms of obsessive-compulsive disorder was not correlated with the severity of baseline depressive symptoms. This study provides additional evidence that the acute serotonin reuptake properties of a drug are predictive of its anti-obsessive-compulsive efficacy. It is hypothesized that the mechanism of action of serotonin reuptake inhibitors in obsessive-compulsive disorder may be related to chronic treatment-induced adaptive changes in presynaptic serotonin receptor function (eg, autoreceptor desensitization) and/or indirect influences on dopaminergic function (eg, in the basal ganglia). PMID- 2112375 TI - Post-traumatic epilepsy. PMID- 2112376 TI - Effects of diethyl maleate (DEM), a glutathione depletor, on prostaglandin synthesis in the isolated perfused spleen of rabbits. AB - To investigate the role of glutathione (GSH) on prostaglandin (PG) synthesis, isolated rabbit spleens were perfused with Tyrode's solution with or without the addition of diethyl maleate (DEM) in concentrations up to 1 mM. In the absence of DEM, PG synthesis was stimulated by the Ca2+ ionophore A23187 (20 nmole) or arachidonate (0.4 mumole). Prostaglandin (PG) E2 was a major product, accounting for 60-70% of the total cyclooxygenase products. Small amounts of PGF2 alpha, 6 keto-PGF1 alpha, PGD2 and thromboxane (Tx) B2 were also produced. When DEM was added to the perfusion medium, GSH content decreased dose-dependently with increasing DEM concentration. Lactate dehydrogenase activity was not detected in the venous effluent, indicating that DEM depleted intrasplenic GSH without causing any lysis of cellular membranes. A23187-induced production of PGs and of Tx was decreased with increasing concentrations of DEM up to 0.5 mM, whereas at 1.0 mM DEM, these products showed a tendency to increase as compared with levels at 0.5 mM DEM. However, this increase was only significant for TxB2, which returned to levels obtained in the absence of DEM. DEM 1 mM did not cause cell lysis, but it appears to perturb the cell membrane to a degree similar to that which occurs with stimulation of phospholipase A2. The small but significant increase of TxB2 with 1.0 mM DEM could be a result of decreased PGE2 isomerase activity. Perfusion with arachidonate gave virtually identical results: 1.0 mM DEM attenuated the production of all prostanoids except for TxB2 as compared with untreated controls. These results suggest that GSH contributes to the regulation and/or maintenance of PGs synthesis. PMID- 2112377 TI - Bovine dental pulp collagens: characterization of types III and V collagen. AB - Pulp was essentially solubilized by partial pepsin digestion. The various genetic types of collagens were isolated by differential salt precipitation and extraction. Types I, III and V collagen represented 56, 41 and 2% of the total collagen, respectively. The type V collagen comprised two different molecular species consisting of [alpha 1(V)]2 alpha 2(V) and alpha 1(V) alpha 2(V) alpha 3(V), the ratio of which was approx. 1:1.3. The major portion of the type III collagen was present as a high molecular weight aggregate which released alpha 1(III) chains upon reduction with 2-mercaptoethanol. PMID- 2112378 TI - In vitro antimicrobial activity of defensins against ocular pathogens. AB - New approaches to antimicrobial therapy for ocular pathogens must overcome organisms that are resistant to current therapeutic modalities. This investigation examined the antimicrobial activity of novel antimicrobial neutrophil peptides (defensins NP-1 and NP-5) against isolates from clinical ocular microbial infections in humans and horses. The test panel of human clinical isolates included Candida albicans, an alpha-hemolytic Streptococcus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Morganella morganii. The test panel of equine pathogens included three clinical isolates of P aeruginosa and two clinical isolates of Staphylococcus aureus. The equine isolates were chosen for their relative resistance to commonly employed antimicrobial therapy. The two defensins differed markedly in their bactericidal activity. Defensin NP 5, at a 50-micrograms/mL concentration, exhibited minimal bactericidal activity against the majority of isolates of the test panel. The inferior microbicidal activity of NP-5 is consistent with previously published results. However, at this concentration, NP-5 did exhibit appreciable bacteriostatic activity against human ocular pathogens M morganii (74%), alpha-hemolytic Streptococcus (57%), and P aeruginosa (93%) during the 2-hour incubation period. In contrast, defensin NP 1 at 10 micrograms/mL exerted potent microbicidal activity against all isolates, effecting a 2 to 3 log10 decrease in colony-forming units within a 60-minute incubation period. Under the assay conditions employed, these findings demonstrate: (1) two distinct mechanisms by which defensins exert their antimicrobial activity against microbial pathogens associated with clinical ocular disease in humans and horses, and (2) that rabbit defensin NP-1 is a potent antimicrobial agent against a wide array of ocular pathogens. PMID- 2112379 TI - Presence of an endo-beta-galactosidase degrading the linkage region between the chondroitin sulfate chain and core peptide of proteoglycan. AB - Pyridylamino chondroitin sulfate, of which the reducing terminal xylose was coupled with a fluorescent 2-aminopyridine, was incubated at pH 4.0 with an extract from the mid-gut gland of Patnopecten. The high- and low-molecular-weight products were separated by ethanol precipitation, and identified by high performance liquid chromatography analysis. The enzyme was found to expose a galactose residue at the reducing terminus of chondroitin sulfate, and also released the pyridylamino disaccharide, galactosylxylose, from the reducing terminal site of pyridylamino chondroitin sulfate. These results suggest that endo-beta-galactosidase activity, which hydrolyzes the galactosylgalactose linkage of peptidochondroitin sulfate, is present in the mid-gut gland of Patnopecten. PMID- 2112380 TI - Isolation and sequencing of rat liver bilirubin UDP-glucuronosyltransferase cDNA: possible alternate splicing of a common primary transcript. AB - A 1763-bp cDNA for rat liver bilirubin UDP-glucuronosyltransferase (UDPGT) was isolated. Bilirubin UDPGT activity was demonstrated by transfection of the pcDL1 vector carrying the cDNA into COS7 monkey kidney cells. The cDNA shares an identical 913-bp sequence (corresponding to the C-terminal 247 amino acid residues) with that for rat liver 3-methylcholanthrene-inducible 4-nitrophenol UDPGT including the locus where a -1 frameshift mutation was found in the 4 nitrophenol UDPGT cDNA from the jaundiced homozygous Gunn rat. The result suggests that both the UDPGTs are derived from a common primary-transcript and that the multiple defects of UDPGT isoenzymes observed in the homozygous Gunn rat may be produced by a single-mutated-locus after an alternative splicing of the 5' end region. PMID- 2112381 TI - Bacillus amyloliquefaciens alpha-amylase signal sequence fused in frame with human proinsulin is properly processed by Bacillus subtilis cells. AB - The plasmid pBINS1, containing the promoter, SD and leader peptide sequences of Bacillus amyloliquefaciens alpha-amylase gene and 267 bp long sequence coding for human proinsulin directs the efficient synthesis of hybrid preproinsulin, as well as quantitative secretion of proinsulin outside of protease-deficient Bacillus subtilis AJ73 cells. The recombinant proinsulin has been isolated from the culture medium and its N-terminal sequence shown to be identical with that of natural human prohormone. PMID- 2112382 TI - The correlation between Ca2+ influx and inositol 1, 4, 5-trisphosphate (IP3) formation in platelets stimulated by various agonists. AB - The relationship between Ca2+ influx (delta [Ca2+]i) and the formation of inositol 1,4,5-trisphosphate (IP3) was investigated in human platelets stimulated by various agonists. Both delta [Ca2+]i and IP3 were increased in proportion to the amount of the agonists (thrombin, ADP, PAF, STA2), the receptors of which were demonstrated in platelets, and were correlated with each other. However, the ratio of delta [Ca2+]i to IP3 was significantly varied among agonists. Furthermore, in thrombin stimulated platelets, IP3 was small at low temperature (20 degrees C) compared with that at high temperature (37 degrees C) in spite of the similar delta [Ca2+]i. Thus, Ca2+ influx in human platelets seems to be regulated directly through the receptor operated mechanism and IP3 may not be involved in it. PMID- 2112383 TI - Tightly-bound form of poly(ADP-ribose)polymerase in the higher order of chromatin organization. AB - A tightly-bound form of poly(ADP-ribose)polymerase is present, within the third level of rat testis chromatin structure, both in the loops and in chromatin matrix. When chromatin matrix was extensively digested with DNAaseI, only little residual enzymatic activity remained in the insoluble fraction, the extent of DNA hydrolysis being well correlated to the progressive loss of the poly(ADP ribose)polymerase activity. These findings suggest that the tightly-bound form of the enzyme is not an intrinsic protein component of chromatin matrix but is only indirectly located in this structure, being rather associated to the attachment points of loop DNA on the matrix. PMID- 2112384 TI - Purification and properties of phospholipase A2 from the venom of scorpion, (Heterometrus fulvipes). AB - Phospholipase A2 was purified about 78 fold from the venom of scorpion Heterometrus fulvipes. The molecular weight of the enzyme was found to be 16,000 and it was optimally active at pH 7.4 and at 50 degrees C. The Km value of the enzyme was 1.8 x 10(-3) M. Calcium, Magnesium and Zinc ions stimulated whereas Mercury ion and EDTA inhibited the enzyme activity. This enzyme exhibited fluorescence emission maximum between 310-320 nm. PMID- 2112385 TI - Preferential binding of cisplatin to mitochondrial DNA and suppression of ATP generation in human malignant melanoma cells. AB - Effects of cisplatin on mitochondria in human malignant melanoma from gingiva were investigated. Cisplatin bound about 50 times more to mitochondrial DNA than to chromosomal DNA. NADH-ubiquinone reductase was decreased 48 h after the administration to about 40% of the initial level, and cellular ATP level was also depressed at that time. A good correlation was observed between the energy status and NADH-ubiquinone reductase activity. These results suggest that the preferential binding of cisplatin to mitochondrial DNA results in the inhibition of NADH-ubiquinone reductase and consequently in the disturbance of ATP generation. PMID- 2112387 TI - The ubiquity of the highly phosphorylated nuclear protein P1. AB - The present work shows that antibodies raised in rabbits against rat liver P1 confirmed the presence of P1 in lung, kidney, brain heart, muscle, intestine and thymus in rats. The antiserum reacted with P1 from human and monkey but not from bovine, pig and mouse P1 in spite of there being a close relationship in amino acid composition, electrophoretic properties and peptide mapping. Proteolytic digestion of rat P1 showed that only some of the peptides produced reacted with the antiserum, suggesting that conformational determinants may be dominating compared to sequential determinants in P1, or that only minor parts of P1 which exhibit sequential variation between species are immunoreactive. PMID- 2112386 TI - Differential effects of fat deficiency on hepatic and pulmonary drug metabolizing enzymes in rat and mouse. AB - In the present study, we have evaluated the effect of dietary fat deprivation on the carcinogen/drug metabolizing enzymes in rats and mice. In rats, hepatic AHH, Cyt.P-450 Cyt.b5 and Cyt.c-reductase were significantly decreased due to fat deficiency, whereas in lungs, AHH and Cyt.c-reductase were decreased without any change in Cyt.P-450 level. In mice, feeding of fat-free diet did not cause any alteration in hepatic AHH and Cyt.P-450, but the levels of Cyt.b5 and Cyt.c reductase were significantly reduced. In contrast to liver, Cyt.P-450 and Cyt.b5 were increased in lungs. Activity of UDPGT was lowered both in liver and lungs of rats whereas GST and GSH were increased in liver only. In mice, a decrease in UDPGT and appreciable increases in GST and GSH in liver were observed. However, in lungs, UDPGT activity was enhanced by feeding fat-free diet. These observations suggest that mice and rats respond differentially to the depletion of fat in the diet. PMID- 2112388 TI - Effect of a high fat/cholesterol diet with or without eicosapentaenoic acid on plasma lipids, lipoproteins and lipid transfer protein activity in the marmoset. AB - Marmosets fed a diet supplemented with 0.2% cholesterol and 10% sheep fat (by weight) developed hypercholesterolemia with a 4-fold increase in plasma cholesterol (4.28 +/- 0.57-16.38 +/- 4.22 mmol/l, mean +/- SD, P less than 0.001). This was due mainly to a 5-fold increase in the intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) fraction (d = 1.006-1.063 g/ml). The proportion of plasma cholesterol in high density lipoproteins (HDL) decreased from 56% to 25% although HDL cholesterol increased from 2.40 +/- 0.42 to 4.09 +/- 0.92 mmol/l (P less than 0.001), and HDL particle radius increased from 5.10 +/- 0.18 nm to 6.06 +/- 0.73 nm (P less than 0.05). Plasma lipid transfer protein (LTP) activity increased 2.5-fold in whole plasma and 2-fold in lipoprotein-deficient plasma. The atherogenic lipoprotein profile was attenuated by adding 0.8% eicosapentaenoic acid (EPA, 20:5 n - 3, as the ethyl ester) to the atherogenic diet. Plasma cholesterol increased only 55% to 6.64 +/- 2.55 mmol/l with only an 80% increase in lipoproteins in the d = 1.006-1.063 g/ml fraction and a more favourable proportion of plasma cholesterol in HDL (44%) than without EPA. LTP activity was reduced to 1.7-fold above control in whole plasma by addition of EPA to the atherogenic diet. There was a positive correlation between plasma cholesterol and LTP activity in whole plasma (r = 0.89, P less than 0.001) and in lipoprotein-deficient plasma (r = 0.67, P less than 0.001). EPA therefore attenuated some of the adverse effects of a 0.2% cholesterol, 10% sheep fat diet on plasma lipids and lipoproteins and induced a less atherogenic profile. PMID- 2112389 TI - Effects of safflower oil and evening primrose oil in men with a low dihomo-gamma linolenic level. AB - Low levels of essential polyunsaturated fatty acids of the n-6 series are associated with coronary heart disease. Linoleic acid, but not gamma-linolenic acid requires the activity of delta 6-desaturase for its conversion to dihomo gamma-linolenic and arachidonic acid. Evening primrose oil (EPO) and safflower oil (SO) are rich in linoleic acid, but EPO contains also 9% gamma-linolenic acid. The effect of EPO (10, 20 and 30 ml/day) and SO (20 ml/day) for 4 months on the deposition of linoleic acid metabolites in adipose tissue of 4 groups of 6-9 men with low adipose dihomo-gamma-linolenic acid was examined. EPO but not SO increased adipose dihomo-gamma-linolenic acid level from 0.080 +/- 0.005% to 0.101 +/- 0.005% (P less than 0.01; 20 ml/day for 4 months). Adipose dihomo-gamma linolenic/linoleic acid ratio increased with EPO from 0.99 +/- 0.16 X 10(2) to 1.13 +/- 0.14 X 10(2) and fell on SO from 1.04 +/- 0.10 X 10(2) to 0.90 +/- 0.07 X 10(2) (P less than 0.01). Similar qualitative changes in the relative amount of dihomo-gamma-linolenic acid in serum triglyceride and cholesteryl ester fractions were observed. At the dose of 20 ml/day, SO and EPO did not differ in their effect on serum cholesterol (7.13 +/- 0.43 vs. 7.33 +/- 0.42 mmol/l (NS)), LDL cholesterol (5.10 +/- 0.32 vs. 4.88 +/- 0.46 mmol/l (NS)) nor did the 2 oils differ in their effect on HDL-cholesterol. These results suggest that linoleic acid is not readily converted to dihomo-gamma-linolenic acid due to a low activity of delta 6-desaturase in these highly selected men. EPO was not an effective hypocholesterolaemic agent in this study. PMID- 2112390 TI - Arctic adaptation in whale hemoglobin: interplay of carbon dioxide and temperature in the oxygen unloading. AB - The functional properties of hemoglobin from the whale Balaenoptera acutorostrata have been characterized as a function of pH, CO2, organic phosphates and temperature. Carbon dioxide effect does not depend on the presence of organic phosphates such as 2,3-DPG and P6-inositol while it is strongly affected by temperature, so that at 37 degrees C it is completely abolished. This, together with the very small delta H of oxygen binding (delta H = -4 to -2 Kcal/mol of oxygen at pH 7.4) has been physiologically interpreted on the basis of the specific metabolic needs of fins and tail which are the place of a great muscular activity. PMID- 2112391 TI - Detection of human immunodeficiency virus in infected CEM cells using fluorescent DNA probes and a laser-based computerized image cytofluorometry system. AB - Quantitative nonradioactive methods to measure the human immunodeficiency virus (HIV) in individually infected cells are needed for the direct assessment of HIV infection, for the evaluation of antiviral chemotherapy and for testing the efficacy of vaccines. As a first step in accomplishing this goal, we built an argon ion laser-based computerized image cytofluorometry (ALCIC) system and determined this instrument's ability to quantitatively measure HIV nucleotides in infected lymphocytes. ALCIC consisted of a 43-mW argon ion laser connected to a Zeiss Universal microscope via a fiberoptic cable, a charged coupled-device video camera, a video frame grabber and array processor and a Micro Vax II computer using computer programs written in FORTRAN. HIV RNA and DNA were detected in infected CEM lymphocytes in culture by in situ hybridization using acetylaminofluorene (AAF)-labeled HIV-DNA probes, a rabbit anti-AAF antibody and a fluorescein-labeled goat anti-rabbit antibody. ALCIC measurements showed that 61% of the CEM cells were infected and that quantitative differences were distinguishable within this group. The levels of fluorescein isothiocyanate (FITC) fluorescence were sixfold or more greater than that observed with the same system using a 100-W mercury lamp for illumination; the improved intensity of the laser-based system is due to greater excitation intensity of the laser and the matching of the excitation spectrum to the peak wavelength of FITC. ALCIC has potential clinical value for determining the effect of antiviral agents on HIV infection and for assessing the susceptibility of different cell types to infection. PMID- 2112392 TI - Impaired peripheral T3 production but normal induced thyroid hormone secretion in the sex-linked dwarf chick embryo. AB - Plasma concentrations of thyroxine (T4), triiodothyronine (T3) and chicken GH (cGH), together with hepatic 5'-monodeiodination (5'-D) activity, were measured in normal (Dw) and dwarf chick (dw) embryos at incubation d 18. An injection of 10 micrograms of ovine GH (oGH) raised plasma concentrations of T3 in Dw embryos after 1 and 2 h and stimulated hepatic 5'-D activity after 2 h. A non-specific increase in T4 was also observed after 1 h in Dw animals probably due to the heterologous nature of the injection. These effects were not observed in dw embryos. An injection of 1 microgram of TRH was able to increase cGH levels after 15 min in Dw embryos, whereas the the observed increase in the dw group was not significant. In Dw embryos, 0.01, 0.1 and 1 microgram of TRH increased plasma concentrations of T3 in a dose-dependent way, whereas in dw embryos, no reaction to the TRH injections was seen, except for the highest dose used. Contrary to this observation, T4 was increased to the same level in both Dw and dw embryos following TRH injections. An injection of 1 microgram of ovine CRH increased corticosterone after 0.5 h and elevated T3 and T4 after 2 h to the same extent in Dw and dw embryos. It is concluded that the thyrotrophic activities of TRH and oCRH and the corticotropic activity of oCRH do not differ between normal and sex linked dwarf embryos. However TRH and GH were unable to stimulate the T4-T3 conversion in the liver of dw embryos, presumably due to the lack of hepatic GH receptors in these animals. PMID- 2112393 TI - Comparison of endotoxins and cutaneous burn toxin as immunosuppressants. AB - Endotoxins of E. coli, S. typhosa and Ps. aeruginosa were injected i.p. into mice a few days before administration of the antigen sheep erythrocytes (SE). Antibody forming cells (AFC) to SE were later enumerated in relation to dose of endotoxin given. In comparison a toxic lipid protein isolated from burned skin (cutaneous burn toxin or CBT) was similarly applied and found to be more inhibitory of the immune response than any of the three endotoxins. Considering the 50 per cent inhibitory doses on a molar basis CBT was found to be 1000 fold more immunosuppressive than the most inhibitory endotoxin. As the immune suppression which follows severe thermal injury involves failure of interleukin 2 (IL2) function, as a critical index of survival, the CBT was tested for its effects on the culture of a human IL2-dependent cell line in the presence of IL2. CBT inhibited the growth of these cells, however, endotoxin had no effect on their proliferation. Thus CBT, which arises by a thermally induced polymerization of skin lipid protein, is specific to burn injury and has a direct inhibitory effect on the immune response. PMID- 2112394 TI - Lipid mediators of the allergic reaction. PMID- 2112395 TI - Introduction of stable high-copy-number DNA into Chinese hamster ovary cells by electroporation. AB - A new gene transfer protocol has been developed that introduces up to 800 copies of an expression vector into Chinese hamster ovary cells in a single step by electroporation. The DNA typically integrates in tandem repeats so that the restriction endonuclease site used to linearize the input DNA remains intact. This is likely due to ligation of vector DNA via cohesive ends prior to integration. This high-copy-number procedure is far more rapid than the conventional stepwise gene amplification method used to generate stable eukaryotic protein production cell lines. By employing the expression vector pJODtPA, in which the selectable marker dihydrofolate reductase (DHFR) and the human tissue plasminogen activator (tPA) casettes are separated by a spacer and an RNA polymerase II terminator, cell lines secreting as much as 24 pg/cell.day tPA were isolated following electroporation and a single methotrexate selection. Gene copies and expression levels are stable over long periods of growth. A single round of gene amplification was performed following the high-copy-number procedure to yield a clone having a tPA production level of 45 pg/cell.day. PMID- 2112396 TI - Susceptibility to AIDS progression appears early in HIV infection. AB - To investigate whether predictors of AIDS progression are operative very early in the natural history of HIV infection, we conducted a nested case-control study within a cohort of 119 subjects who seroconverted while under observation in a prospective study of homosexual men. For each of the 18 cases who have progressed to AIDS, we randomly selected three controls who had seroconverted within 3 months of the case but who have remained AIDS-free. Cases and controls were compared with regard to laboratory and clinical parameters obtained at the time of the earliest HIV-positive result. The median duration between the estimated date of seroconversion and this first positive result was 4 months for cases and 6 months for controls. Cases exhibited lower CD4 counts (657 versus 774 x 10(6)/l; P = 0.037), lower CD4: CD8 ratios (0.98 versus 1.39; P = 0.003), higher immune complex levels (C1q binding: 25 versus 15%; P = 0.002), lower hemaglobin concentrations (14.8 versus 15.2 g/l; P = 0.011), higher immunoglobulin (Ig) A levels (272 versus 184 mg/dl; P = 0.003), and higher IgG levels (1530 versus 1300 mg/dl; P = 0.037) than controls. Cases exhibited higher CD8 counts of marginal statistical significance (732 versus 597 x 10(6)/l; P = 0.059). No differences were observed with respect to IgM levels, total lymphocyte or white blood cell counts, or the frequency of generalized lymphadenopathy. A total of 27.8% of cases but only 11.5% of controls reported one or more symptoms during the 6-month period preceding the first positive visit (P = 0.027). We conclude that laboratory and clinical abnormalities which are predictive of more rapid progression to AIDS may appear very early in HIV infection. This suggests that some of the factors responsible for more rapid disease progression are present in the host prior to or shortly after infection occurs. PMID- 2112397 TI - Macrophage-HIV interaction: viral isolation and target cell tropism. AB - Viral isolates were recovered by cocultivation on macrophage colony stimulatingfactor (MCSF)-treated monocyte target cells from peripheral blood mononuclear cells (PBMCs) in 25 out of 27 patients seropositive or at risk for HIV infection. Frequency of virus recovery was independent of the patient's age, sex, numbers of CD4+ T cells, clinical stage or zidovudine (azidothymidine) therapy. Sixteen out of 19 HIV isolates were serially passaged in MCSF- treated monocytes. Five out of five virus isolates were also passaged in phytohemagglutinin/interleukin-2 (PHA/IL-2)-treated lymphoblasts. In lymphoblasts, no qualitative or quantitative differences were observed between these isolates and human T-cell leukemia virus IIIB (HTLV-IIIB) for (1) release of p24 antigen reverse transcriptase, and infectious virus, (2) induction of typical cytopathic effects (cell syncytia in 3-10% of cells) and cell lysis, (3) frequency of infected cells (5-20% of PBMC) as detected by in situ hybridization for HIV RNA, (4) down-modulation of T cell plasma membrane CD4, and (5) site of progeny virion assembly and budding (plasma membrane only with no intracytoplasmic accumulation of virus). Progeny virus recovered from infected lymphoblasts was fully infectious for other lymphoblasts, but failed to infect MCSF-treated monocytes. Detailed analysis of target cell tropism among HIV isolates showed that HIV isolated in monocytes infected both monocytes and lymphoblasts; progeny virus isolated in lymphoblasts infected only T cells. HIV interacts differently with monocytes and T cells. Understanding this interaction may more clearly define both the pathogenesis of HIV disease and strategies for therapeutic intervention. PMID- 2112398 TI - Transfer of arachidonic acid from phosphatidylcholine to phosphatidylethanolamine during storage of human platelets for 5 days. AB - Human platelets are routinely stored for 5 days prior to transfusion, but they deteriorate during storage. Since very little information is available concerning the effect of storage on platelet phospholipid metabolism, the biosynthesis and remodelling of platelet phospholipids were studied. Platelets were incubated separately with [14C]glycerol, [14C]arachidonic acid, or a mixture of [14C]glycerol and [3H]arachidonic acid, and stored in a platelet storage medium at 22 degrees C. Maximum glycerol uptake (20%) was attained after 6 h. [14C]Glycerol was incorporated into phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, and to a much lesser extent phosphatidylserine, under storage conditions for 5 days. The distribution of the initial arachidonic acid uptake was not as would be expected based on the molar composition of endogenous phospholipids. The arachidonic acid (75%) which was taken up within 10 min of incubation distributed 55% into the phosphatidylcholine and only 14% into the phosphatidylethanolamine; the molar composition is actually 18% phosphatidylcholine and 47% phosphatidylethanolamine. During storage, there was a continuous transfer of the radiolabelled arachidonic from phosphatidylcholine to phosphatidylethanolamine until, after 5 days, the distribution of arachidonic acid was identical to the endogenous distribution. In contrast, no change in the glycerol incorporation pattern was detected during storage. This suggested that the mechanism for arachidonic acid redistribution was not through exchange of polar head groups, but through acyl transfer of arachidonic acid from phosphatidylcholine to phosphatidylethanolamine. PMID- 2112399 TI - Inhibition of enzymatic degradation of angiotensin II in membrane binding assays: utility of 1,10-phenanthroline. AB - Studies of 125I-labelled angiotensin II binding to membranes from bovine uterus and aorta are rendered impossible because enzymatic degradation of 90% of the added ligand occurs within 30 min at 23 degrees C. High pressure liquid chromatographic analysis has demonstrated that a single iodinated product, which is more hydrophilic than intact angiotensin II, is produced by enzymatic cleavage. Investigation of a series of enzyme inhibitors has shown that the carboxypeptidase inhibitor 1,10-phenanthroline completely inhibits degradation of angiotensin II without disrupting ligand binding. PMID- 2112400 TI - Oxidation of 2-oxoisocaproate and 2-oxoisovalerate by the perfused rat heart. Interactions with fatty acid oxidation. AB - The interactions between fatty acid oxidation and the oxidation of the 2-oxo acids of the branched chain amino acids were studied in the isolated Langendorff perfused heart. 2-Oxoisocaproate inhibited the oxidation of oleate, but 2 oxoisovalerate and 2-oxo-3-methylvalerate did not. This difference was not attributable to the magnitude of the flux through the branched chain 2-oxo acid dehydrogenase, which was slightly higher with 2-oxoisovalerate than with 2 oxoisocaproate. Oxidation of 2-oxoisocaproate in the perfused heart was virtually complete, since more than 80% of the isovaleryl-CoA formed from 2-oxo[1 14C]isocaproate was further metabolized to CO2, as determined by comparing 14CO2 production from 2-oxo[14C(U)]isocaproate with that from the 1-14C-labelled compound. Only twice as much 14CO2 was produced from 2-oxo[14C(U)]isovalerate as from the 1-14C-labelled compound, indicating incomplete oxidation. This was confirmed by the accumulation in the perfusion medium of substantial quantities of labelled 3-hydroxyisobutyrate (an intermediate in the pathway of valine catabolism), when hearts were perfused with 2-oxo[14C(U)]isovalerate. The failure of 2-oxoisovalerate to inhibit fatty acid oxidation, then, can be attributed to the fact that its partial metabolism in the heart produces little ATP. We have previously shown that 3-hydroxyisobutyrate is a good gluconeogenic substrate in liver and kidney, and postulate that 3-hydroxyisobutyrate serves as an interorgan metabolite such that valine can serve as a glucogenic amino acid, even when its catabolism proceeds beyond the irreversible 2-oxo acid dehydrogenase in muscle. PMID- 2112401 TI - A halophilic extracellular protease from a halophilic archaebacterium strain 172 P1. AB - An unidentified halophilic archaebacterium strain 172 P1 produced three extracellular proteases in media containing 15-27% salts. One component, F-II, was purified to homogeneity. It is a serine protease that can be inhibited by phenylmethylsulfonyl fluoride and chymostatin. A high concentration of NaCl was required for its stability; in the presence of 25% NaCl, only 4% of the activity was lost by incubating at 60 degrees C for 30 min, while complete inactivation occurred in the presence of 5% NaCl. F-II is a thermophilic and halophilic protease. High activity was obtained at 75-80 degrees C when F-II was assayed in the presence of 25% NaCl. The optimal concentration of NaCl required was 10-14% when assayed at 70 degrees C with azocasein as substrate, though a halophilic characteristic was not distinct at lower temperatures. Hydrolyses of the synthetic substrates succinyl-alanyl-alanyl-prolyl-phenylalanyl-4-methylcoumaryl 7-amide or succinyl-alanyl-alanyl-alanyl-p-nitroanilide at 26 degrees C were maximal at 25 and 30% NaCl, respectively. F-II was most stable at pH 6-7, and its optimal pH was 10.7. Its molecular weight was estimated as 44,000-46,000 by sodium dodecyl sulfate--polyacrylamide gel electrophoresis and by gel filtration- high-pressure liquid chromatography. The sequence of the 35 N-terminal amino acid residues was determined and compared with that of other serine proteases. PMID- 2112403 TI - Respiratory responses of domestic fowl to hyperthermia following selective air sac occlusions. AB - Ventilation together with blood and respiratory gas tensions were measured in adult domestic fowl under normothermic and hyperthermic conditions, following bilateral occlusion of the cranial and caudal thoracic air sacs (series I) or the cranial and caudal thoracic plus the abdominal air sacs (series II). Series I birds showed no significant differences from controls. Both control and experimental animals displayed a typical thermal polypnoea combined with mild hypocapnaemia. A larger drop in PCO2 was demonstrated in the clavicular sac than in the blood, possibly indicating partial failure of inspiratory valving at the ventrobronchi. However, there was no evidence of any effect of thoracic air sac occlusion on inspiratory airflow valving in the palaeopulmo. Series II birds were strongly hypercapnaemic/hypoxaemic in normothermic conditions, with a normal minute volume, but a faster, shallower breathing pattern. During hyperthermia they increased minute ventilation 3-fold, as in control animals, and blood gas tensions were almost restored to normal. Again, there was no evidence that experimental reduction in air sac capacity, in this case up to 70% of the total, had any effect on inspiratory airflow valving in the palaeopulmo, although inevitably in this case airflow in the neopulmo was abolished. PMID- 2112402 TI - The influence of acute venous congestion on the guinea pig cochlea. AB - The effects of sudden occlusion of the vein of the cochlear aqueduct (VCAQ) on the cochlear blood flow, endocochlear potential (EP), endolymphatic and perilymphatic fluid pressures (PE and PP) were studied in the guinea pig. Cochlear blood flow showed a sudden decrease, and EP began to drop within 90 s, ranging from 50 to 70 mV in 5 of 11 animals studied, recovering to normal levels when the animals were placed on a continuous inhalation of carbogen. The PE and PP increased simultaneously (max. PE = 3.4 +/- 1.4 mm Hg; max. PP = 2.5 +/- 1.0 mm Hg) and returned to their initial values after 5 min. The EP was sustained within the normal range, even when there was an apparent decrease in cochlear blood flow (61.4 +/- 8.4%). We believe that variations in EP following VCAQ occlusion were due to anatomical differences in collateral venous communications among the animals studied. Carbogen inhalation produced uniform recovery patterns, indicating that individual collateral vessel responses were eliminated. PMID- 2112404 TI - Some methodologic considerations in nursing diagnosis research. AB - The validation of nursing diagnostic concepts, interventions, and desired outcomes is necessary for the development of nursing science. The purpose of this article is to contribute to the development of more rigorous methods for research of nursing diagnoses. Methodologic problems and issues are discussed and illustrated in the context of a descriptive study of the nursing diagnoses of patients at a large long-term care facility. Issues surrounding the selection of setting and samples, the source and presentation of data collected, and methods used for data analysis and interpretation are described. The need for consistency among research questions, setting and sample, data collection methods, and data analysis and interpretation are emphasized. Researchers are encouraged to explicate the issues and decisions in nursing diagnosis research to encourage scholarly criticism and refinement by clinicians and scientists. PMID- 2112405 TI - The effects of flosequinan on submaximal exercise in patients with chronic cardiac failure. AB - 1. Twenty patients with moderate to severe chronic cardiac failure were entered into a double-blind parallel group study comparing flosequinan 100 mg daily with matching placebo. 2. After at least three prior exercise tests, cardiopulmonary parameters were assessed at rest and during submaximal exercise before and after 2 and 8 weeks of active drug or placebo. 3. Resting minute ventilation and respiratory rate were reduced by flosequinan compared with placebo, but oxygen uptake was unchanged. 4. Comparison of minute ventilation, carbon dioxide production and venous lactate levels at the end of the exercise stage approximating to 50% of peak oxygen uptake demonstrated significant reductions in the flosequinan group compared with placebo at week 2 and week 8 (P less than 0.05). 5. Flosequinan increased the oxygen uptake at anaerobic threshold from 13.2 +/- 2.8 ml min-1 kg-1 to 15.9 +/- 3.4 ml min-1 kg-1 at week 2 and 15.8 +/- 3.7 ml min-1 kg-1 at week 8. These increases were significant when compared with placebo (P less than 0.05). 6. We conclude that flosequinan improves submaximal exercise performance in patients with chronic cardiac failure, probably by enhancing skeletal muscle blood flow. PMID- 2112406 TI - Initiation of in vivo protein synthesis with non-methionine amino acids. AB - Methionine is the universal amino acid for initiation of protein synthesis in all known organisms. The amino acid is coupled to a specific initiator methionine tRNA by methionyl-tRNA synthetase. In Escherichia coli, attachment of methionine to the initiator tRNA (tRNA(fMet)) has been shown to be dependent on synthetase recognition of the methionine anticodon CAU (complementary to the initiation codon AUG), [Schulman, L. H., & Pelka, H. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 6755-6759]. We show here that alteration of the anticodon of tRNA(fMet) to GAC or GAA leads to aminoacylation of the initiator tRNA with valine or phenylalanine. In addition, tRNA(fMet) carrying these amino acids initiates in vivo protein synthesis when provided with initiation codons complementary to the modified anticodons. These results indicate that the sequence of the anticodon of tRNA(fMet) dictates the identity of the amino acid attached to the initiator tRNA in vivo and that there are no subsequent steps which prevent initiation of E. coli protein synthesis by valine and phenylalanine. The methods described here also provide a convenient in vivo assay for further examination of the role of the anticodon in tRNA amino acid acceptor identity. PMID- 2112407 TI - Electron transfer between primary and secondary donors in Rhodospirillum rubrum: evidence for a dimeric association of reaction centers. AB - Light-induced oxidation of the primary electron donor P and of the secondary donor cytochrome c2 was studied in whole cells of Rhodospirillum rubrum in the presence of myxothiazole to slow down their reduction. 1. The primary and secondary electron donors are close to thermodynamic equilibrium during continuous illumination when the rate of the electron transfer is light-limited. This implies a long-range thermodynamic equilibration involving the diffusible cytochrome c2. A different behavior is observed with Rhodobacter sphaeroides R26 whole cells, in which the cytochrome c2 remains trapped within a supercomplex including reaction centers and the cytochrome b/c complex [Joliot, P., et al. (1989) Biochim. Biophys. Acta 975, 336-345]. 2. Under weak flash excitation, the reduction kinetics of the photooxidized primary donor are nearly exponential with a half-time in the hundred microseconds time range. 3. Under strong flash excitation, the reduction of the photooxidized primary donor follows a second order kinetics. About half of the photooxidized primary donor is reduced in a few milliseconds while the remainder stays oxidized for hundreds of milliseconds despite an excess of secondary donors in their reduced form. The flash intensity dependence of the amplitude of the slow phase of P+ reduction is proportional to the square of the fraction of reaction centers that have undergone a charge separation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2112408 TI - Evidence for allosteric coupling between the ribosome and repressor binding sites of a translationally regulated mRNA. AB - Escherichia coli ribosomal protein S4 is a translational repressor regulating the expression of four ribosomal genes in the alpha operon. In vitro studies have shown that the protein specifically recognizes an unusual mRNA pseudoknot secondary structure which links sequences upstream and downstream of the ribosome binding site for rpsM (S13) [Tang, C. K., & Draper, D. E. (1989) Cell 57, 531]. We have prepared fusions of the rpsM translational initiation site and lacZ that allows us to detect repression in cells in which overproduction of S4 repressor can be induced. Twenty-five mRNA sequence variants have been introduced into the S13-lacZ fusions and the levels of translational repression measured. Sets of compensating base changes confirm the importance of the pseudoknot secondary structure for translational repression. An A residue in a looped, single-stranded sequence is also required for S4 recognition and may contact S4 directly. Comparison of translational repression levels and S4 binding constants for the set of mRNA mutations show that nine mutants are repressed much more weakly than predicted from their affinity for S4; in extreme cases no repression can be detected for variants with unchanged S4 binding. We suggest that the mRNA contains functionally distinct ribosome and repressor binding sites that are allosterically coupled. Mutations can relieve translational repression by disrupting the linkage between the two sites without altering S4 binding. This proposal assigns to the mRNA a more active role in mediating translational repression than found in other translational repression systems. PMID- 2112409 TI - New evidence for the dimeric nature of NADH:Q oxidoreductase in bovine-heart submitochondrial particles. AB - The initial velocity of NADH oxidation by bovine-heart submitochondrial particles was measured at pH 8.0 after pretreatment of these particles with different amounts of the inhibitor piericidine A together with 0.035 mM NADH. The amount of piericidine A required to fully inhibit the NADH oxidation activity extrapolated to exactly 1.0 per Fe-S cluster 2 of NADH:Q oxidoreductase. When no reducing equivalents from NADH were present during the pretreatment, this ratio was 1.2. The difference is explained by assuming that NADH:Q oxidoreductase binds piericidine A more effectively in the reduced state than in the oxidized state. It was also found that after Q10-extraction and reincorporation of submitochondrial particles, the amount of piericidine A required to fully inhibit the NADH oxidation activity of the particles increased with the amount of Q10 present during reincorporation. This is explained by assuming that binding of piericidine A, to the inhibitory site of NADH:Q oxidoreductase requires Q10. When 0.035 mM NADPH instead of NADH was present during the pretreatment of submitochondrial particles with piericidine A, the amount of inhibitor per cluster 2 required to fully inhibit the initial NADH-oxidation activity extrapolated to 0.5. This result strongly suggests that NADH:Q oxidoreductase is a functional dimer. PMID- 2112410 TI - A note on case-control sampling to estimate kappa coefficients. AB - The feasibility and cost-effectiveness of estimation of kappa using a case control method of sampling, proposed by Jannarone, Macera, and Garrison (1987, Biometrics 43, 433-437), is provided support. However, in this article unrealistic assumptions in their presentation are identified and more general results for more realistic settings are provided. PMID- 2112411 TI - Glycoprotein IIIa is phosphorylated in intact human platelets. AB - The glycoprotein IIb-IIIa complex (GP IIb-IIIa) is a multifunctional transmembrane protein on platelets. Its most completely described function is as a fibrinogen receptor that mediates platelet aggregation, but it is also involved in clot retraction, signal transduction, calcium transport, and other events. However, the mechanisms that regulate the functions of GP IIb-IIIa during platelet activation are largely unknown. One possible mechanism is phosphorylation, since several other receptors are regulated by this process. We found that GP IIIa, but not GP IIb, was phosphorylated in 32P-labeled platelets, predominantly on threonine residues. Furthermore, GP IIIa phosphorylation increased four-fold in platelets activated with thrombin or phorbol 12-myristate 13-acetate, but not at all in platelets treated with prostacyclin, an inhibitor of platelet activation. The thrombin-induced increase in phosphorylation was inhibited by pretreating platelets with prostacyclin or with staurosporin, a specific protein kinase C inhibitor. Thus, there is an increase in the level or turnover of phosphate on GP IIIa during platelet activation, most likely involving protein kinase C. This phosphorylation may regulate some aspect(s) of GP IIb-IIIa function. PMID- 2112412 TI - Interferon gamma increases in vitro and in vivo expression of C1 inhibitor. AB - C1 inhibitor (C1 INH) is the major protease inhibitor of the first components of the classic complement system and of the proteases of the Hageman factor pathways. Since C1 INH may modulate inflammatory reactions associated with complement and contact system activation, we sought to determine if the cytokine gamma interferon (IFN-gamma) could modulate C1 INH production. Initial studies investigated the effect of IFN-gamma on the molecular and protein expression of C1 INH in human erythroleukemia (HEL) cells. HEL cells constitutively expressed the 2.1 kb mRNA for C1 INH. IFN-gamma (50 to 1,000 U/mL), but not interferon alpha or beta, increased twofold the amount of C1 INH mRNA expressed within HEL cells. Similarly, this cytokine increased HEL cell C1 INH synthesis of a 105 Kd protein 10-fold, from 1.9 +/- 0.5 microgram C1 INH antigen per 10(8) cells (mean +/- SEM) to 19 +/- 8 micrograms/10(8) cells in 8 days. C1 INH produced by HEL cells after IFN-gamma stimulation had fully intact kallikrein neutralizing activity. Moreover, conditioned media of IFN-gamma-treated HEL cells accumulated more secreted C1 INH in 8 days (6.7 micrograms/mL/10(8) cells) than untreated cells (0.6 microgram/mL/10(8) cells). Additional studies were done on plasma specimens from 22 patients with metastatic colorectal carcinoma who received IFN gamma daily for 4 days by intravenous infusion. Before treatment, the mean +/- SEM C1 INH levels in these patients was 438 +/- 16 micrograms/mL. At day 10 from the start of the infusion, the plasma C1 INH in these patients increased to 586 +/- 32 micrograms/mL (P less than .0001). The extent of rise of plasma C1 INH after IFN-gamma treatment was independent of dose from 0.01 to 40 U/m2. After 30 days, the mean plasma C1 INH levels decreased to 502 +/- 27 micrograms/mL. These combined studies indicate that IFN-gamma can increase C1 INH protein expression in vitro and in vivo. PMID- 2112413 TI - Effects of leukocyte activation on myocardial vascular resistance. AB - The contribution of the leukocyte, particularly the granulocyte, to the tissue injury resulting from the inflammatory response accompanying organ ischemia is a subject of intense, current interest. Leukocytes are large and viscous cells which adhere to vascular endothelium, and are a source of a variety of toxic and vasoactive substances. There are several lines of evidence indicating their involvement in the development of abnormal and heterogeneous tissue perfusion in a wide variety of pathologic states. They have been implicated in the capillary stasis and no-reflow following hemorrhagic shock, and in ischemia and reperfusion of skeletal muscle, brain, and heart. The mechanisms responsible for the detrimental influence of the granulocyte on tissue perfusion include their inherent rheologic properties, their role in the generation of vascular smooth muscle-constricting substances, and their potential for damaging vascular endothelium. One contributing aspect of the inflammatory response is leukocyte activation by products of the complement cascade. In our in vivo model system, stimulation of the granulocyte with activated complement C5a (intracoronary) is associated with myocardial ischemia and a transient myocardial accumulation of granulocytes. The enhanced generation of thromboxane A2 and leukotrienes appears to be primarily responsible for this increase in coronary vascular resistance. PMID- 2112414 TI - Sensitivity of chronic myeloid leukemia hemopoietic progenitors to PTT-119 in combination with human recombinant interferon alpha and gamma. AB - PTT-119, a new synthetic alkylating compound, has shown a marked "in vitro" inhibitory effect on chronic myeloid leukemia (CML) granulo-monocytic precursors (CFU-GM) at doses greater than 5 micrograms/ml. Based on previous experiences of synergistic associations between alkylating drugs and biological modifiers, we tested the effects of low doses of PTT-119 (from 0.1 to 1 microgram/ml) in concert with alpha, gamma, or alpha + gamma interferons and compared to IFNs alone, in order to investigate an alternative choice for treatment of CML patients in chronic phase. Our results showed a significantly higher CFU-GM cloning inhibition after addition of 100 or 1,000 U/ml of alpha IFN to 0.1 microgram/ml PTT-119 (from 39.6% +/- 26.6 SD to 80.7% +/- 10 SD and 91.5% +/- 8 SD, respectively), while gamma IFN resulted in only a slight increase in colony growth inhibition when compared to the drug used alone. The association of alpha plus gamma IFN coupled with PTT-119 treatment did not significantly improve the results observed after exposure of leukemic progenitors to PTT-119 and alpha IFN alone. We conclude that a combined treatment with PTT-119 and IFN is probably worth testing both for purging methods before autologous bone marrow transplantation and for in vivo administration in chronic myeloid leukemia. PMID- 2112415 TI - Double negative (CD4/CD8) T cell receptor alpha/beta positive lymphocytes in patients with graft-versus-host disease. PMID- 2112416 TI - The effect of intraventricular administration of the 5-HT3 receptor agonist 2 methylserotonin on the release of dopamine in the nucleus accumbens: an in vivo chronocoulometric study. AB - In the present study we have examined the effects of the serotonin3 (5-HT3) agonist 2-methylserotonin (2-Me-5HT) on the dopamine (DA) release in the nucleus accumbens (NAc) of rats using in vivo chronocoulometric recording. The intraventricular (i.c.v.) administration of 2-Me-5HT dose-dependently increased the DA release in the NAc. This effect was blocked by the selective 5-HT3 antagonist BRL-43694 (granisetron), but not by the 5-HT1/5-HT2 antagonist metergoline. The i.c.v. injection of 8-hydroxydipropylaminotetraline (8-OHDPAT, a selective 5-HT1a agonist) or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a 5-HT2/5-HT1c agonist) failed to alter the DA release in the NAc. The increase in the DA release produced by 2-Me-5HT was abolished in animals that had received acute bilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our results suggest that the 2-Me-5HT-induced DA release in the NAc is mediated by 5-HT3 receptors. In addition, 2-Me-5HT induced effect is dependent upon the impulse flow of DA cells. PMID- 2112418 TI - [Demonstration of new substances released during acute inflammatory processes]. AB - Various acute inflammatory reactions modify effector and immunoregulatory functions of neutrophils, macrophages and lymphocytes locally as well as at distance from the inflammatory focus. Non-specific defenses are augmented concomitantly. These phenomena have been related to low molecular weight peptides called phlogokines. These findings may contribute to a better knowledge of the inflammatory process, while phlogokines may be of potential therapeutic value. PMID- 2112417 TI - Neurite-like outgrowth from CNS explants may not always be of neuronal origin. AB - In living explants of the developing CNS 'true' neurites (neuronal processes) may appear virtually indistinguishable from the processes of radial and Bergmann glia. This inability to clearly distinguish the phenotype of responsive 'neurites' in the living state has profound implications for the interpretation of responses to 'neurite-promoting' substances. Labeling techniques, specific for intermediate filament proteins that are characteristic of neurons and neuroglia, should always be used to supplement morphologic observations on neurite-like outgrowth from living CNS explants. PMID- 2112419 TI - A mouse embryonic stem cell line showing pluripotency of differentiation in early embryos and ubiquitous beta-galactosidase expression. AB - For analysis of chimeric mice made by injecting embryonic stem (ES) cells into host blastocysts, it is very desirable if the ES cells have a good cell marker that can distinguish them from host cells. It is ideal if the marker can be easily visualized in every type of cell and tissue throughout the embryogenesis. We tried to produce such ES cell lines by introducing an E. coli beta galactosidase (beta-gal) gene construct by electroporation. One of the transformant lines (MS1-EL4) showed beta-gal activity in every undifferentiated stem cell. After being induced to differentiate in vitro, cells with various morphologies showed beta-gal activity. We also detected beta-gal activity in a wide variety of tissue elements in solid tumors made by injecting the MS1-EL4 cells into syngeneic mice. Then we produced chimeric embryos by injecting the MS1 EL4 cells into blastocysts and recovering the embryos at various developmental stages. We found that the MS1-EL4 cells contributed to various tissues and expressed beta-gal activity, including not only descendants of the inner cell mass but also the trophectoderm-derived extraembryonic ectoderm. PMID- 2112420 TI - Cell lineage analyses of epithelia and blood vessels in chimeric mouse embryos by use of an embryonic stem cell line expressing the beta-galactosidase gene. AB - We have established an embryonic stem (ES) cell line, MS1-EL4, which has the potential to make various tissues in chimeric embryos and, at the same time, expresses the beta-galactosidase gene which was introduced as a good cell marker. To examine cell behavior and lineage during embryogenesis, we injected MS1-EL4 cells into host blastocysts and recovered chimeric embryos at various developmental stages. We examined the distribution of the MS1-EL4 cell derivatives by staining whole embryos with X-gal and by making serial paraffin sections. So far we have obtained the following results: (1) the MS1-EL4 cell line is useful for studying cell lineages because of its ubiquitous expression at least until the mid-gestation stage; (2) cells of the primitive ectoderm and its derivative epithelial tissues continue to intermingle with each other until the late primitive streak stage. Then, at early somite stages, cells of various epithelia stop intermingling and give rise to small coherent clones; (3) blood vessels of the yolk sac are formed by local aggregation of the ancestor cells and those of the embryo proper by proliferation and sprouting from fewer angiogenic cells. PMID- 2112421 TI - Spatio-temporal distribution of the adherens junction-associated molecules vinculin and talin in the early avian embryo. AB - To gain an insight into the possible involvement of the cytoskeletal components and cellular junctions in morphogenetic processes during development, we have studied the spatio-temporal distribution of two major adherens-junction associated molecules, vinculin and talin, during avian embryogenesis, using immunofluorescence microscopy and immunoblotting. Both molecules were detected at very early stages during morphogenesis and were found in a wide variety of tissues deriving from the three primary germ layers. A number of tissues, including smooth and striated muscles, endothelia, and some hemopoietic precursors, expressed vinculin and talin at especially high levels either transiently or permanently. Conversely, only a few cell types, e.g., circulating erythrocytes and neurones in the central nervous system lacked or expressed them at very low levels. In addition, expression of vinculin and talin was in some cases modulated in connection with morphological rearrangements of tissues. In particular, they were transiently enhanced in restricted areas of the ectoderm and endoderm undergoing extensive foldings. However, other morphogenetic events such as local disruptions of epithelia were not accompanied by extensive modifications in their expression. Finally, it appeared that, in most cases, vinculin and talin overlapped in their distribution, and the level of their expression was regulated coincidently with the notable exceptions of the primordium of the central nervous system, the nephron, and the liver where each molecule followed independent regulatory patterns. It appears from this study that the spatio-temporal distribution of vinculin and talin correlates frequently with that of the adhesion molecules A-CAM (or N-cadherin), L-CAM, and of integrin receptors. Thus, vinculin and talin, in association with the membrane components of adherens junctions, may actively participate both in the control of cellular interactions during early embryonic development and in cell differentiation. PMID- 2112422 TI - Feeding jejunostomy: a safe adjunct to laparotomy. AB - It is well established that a feeding jejunostomy is an invaluable adjuvant for use in critically ill and malnourished patients. What is not well known are the complications of inserting these tubes. Some surgeons are reluctant to insert feeding tubes unless the indications are very clear. From their experience with the insertion of 133 feeding jejunostomy tubes during a 3-year period, the authors conclude that the complications associated with the insertion of such tubes are few and that the procedure is justified even if the tube is never used. PMID- 2112423 TI - Transforming growth factor-beta and ovarian carcinoma cells: regulation of proliferation and surface antigen expression. AB - Transforming growth factor-beta (TGF-beta) is a multifunctional peptide regulating several processes in ovarian cells. The growth of ovarian carcinoma cell lines (OVCAR-3, HTB-77, 2780 and CRL-1572) was reduced by TGF-beta in a dose related manner. The antiproliferative activity was not improved by combination with other biological response modifiers. Treatment with TGF-beta augmented the expression of interferon-gamma induced class I and II antigens of the major histocompatibility complex. The presentation of another antigen namely the tumor marker CA-125 on the cell surface was markedly reduced by TGF-beta. PMID- 2112424 TI - Mouse skin ornithine decarboxylase induction and tumor promotion by cyclohexane. AB - Cyclohexane, a frequently used solvent in industry, was assessed for its tumorigenic potential on mouse skin following multistage initiation-promotion protocols. The activity of ornithine decarboxylase (ODC), a marker of tumor promotion was found to be induced by the topical application of cyclohexane. This ODC induction was dependent on the dose of cyclohexane used and the duration of application. Effect of protein synthesis inhibitors and the modifiers of tumor promotion on the cyclohexane induced ODC activity was also studied. ODC induction was inhibited by cycloheximide and also, up to some extent, by actinomycin D. Inhibitors of stage II tumor promotion showed more effect on the ODC induction by cyclohexane as compared to the inhibitors of stage I tumor promotion. In chronic animal bioassay experiments topical application of cyclohexane to DMBA initiated mouse skin resulted in just 10% of tumor bearing animals while prior application of TPA for two weeks resulted in 45% of tumor bearing animals. Collectively, the present study demonstrates that cyclohexane is more effective as a stage II tumor promoter over mouse skin and possibly affects the biochemical events at the molecular level. PMID- 2112425 TI - A putative GTP binding protein homologous to interferon-inducible Mx proteins performs an essential function in yeast protein sorting. AB - Members of the Mx protein family promote interferon-inducible resistance to viral infection in mammals and act by unknown mechanisms. We identified an Mx-like protein in yeast and present genetic evidence for its cellular function. This protein, the VPS1 product, is essential for vacuolar protein sorting, normal organization of intracellular membranes, and growth at high temperature, implying that Mx-like proteins are engaged in fundamental cellular processes in eukaryotes. Vps1p contains a tripartite GTP binding motif, which suggests that binding to GTP is essential to its role in protein sorting. Vps1p-specific antibody labels punctate cytoplasmic structures that condense to larger structures in a Golgi-accumulating sec7 mutant; thus, Vps1p may associate with an intermediate organelle of the secretory pathway. PMID- 2112426 TI - Phospholipase C-mediated hydrolysis of phosphatidylcholine is an important step in PDGF-stimulated DNA synthesis. AB - Recent evidence suggests the involvement of phosphatidylcholine (PC) hydrolysis both in the control of normal cell growth and in transformation. We show here that the simple exogenous addition of Bacillus cereus PC-hydrolyzing phospholipase C (PC-PLC) is sufficient to elicit a potent mitogenic response in Swiss 3T3 fibroblasts by a mechanism that is independent of protein kinase C. Our results on the additivity and synergism between B. cereus PC-PLC, PDGF, and insulin in the mitogenic response indicate that this novel phospholipid degradative pathway may be important in the mitogenic signaling cascade activated by PDGF. PMID- 2112427 TI - Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. AB - An A to G transition mutation at nucleotide pair 8344 in human mitochondrial DNA (mtDNA) has been identified as the cause of MERRF. The mutation alters the T psi C loop of the tRNA(Lys) gene and creates a CviJI restriction site, providing a simple molecular diagnostic test for the disease. This mutation was present in three independent MERRF pedigrees and absent in 75 controls, altered a conserved nucleotide, and was heteroplasmic. All MERRF patients and their less-affected maternal relatives had between 2% and 27% wild-type mtDNAs and showed an age related association between genotype and phenotype. This suggests that a small percentage of normal mtDNAs has a large protective effect on phenotype. This mutation provides molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production. PMID- 2112428 TI - NSP1: a yeast nuclear envelope protein localized at the nuclear pores exerts its essential function by its carboxy-terminal domain. AB - NSP1 is located at the nuclear periphery in yeast and is essential for cell growth. Employing immunoelectron microscopy on yeast cells, we show that NSP1 is located at the nuclear pores. The molecular analysis of the NSP1 protein points to a two domain model: a nonessential domain (the first 603 amino acids) composed of repetitive sequences common to other nuclear proteins and an essential, carboxy-terminal domain (residues 604-823) mediating the vital function of NSP1. The NSP1 carboxy-terminal domain, which shows a heptad repeat organization, affected the correct location of two nuclear proteins: site-specific amino acid substitutions within a predicted alpha-helical structure of this domain caused a temperature-sensitive growth arrest at 37 degrees C and the appearance of NSP1 and NOP1, a nucleolar protein, in the cytosol. PMID- 2112429 TI - [Personal experience with the use of Bretschneider's solution and the modified St. Thomas solution in cardioplegic protection of the myocardium]. PMID- 2112430 TI - [Pulmonary arterial hypertension due to bilharziasis. Apropos of a case due to Schistosoma haematobium having been cured by praziquantel]. AB - A case of cardiopulmonary bilharziasis is studied in a female, 21 years old, from Senegal, infested by Schistosoma haematobium. With praziquantel, the patient was cured in 16 months. The cardiopulmonary bilharziasis is more frequent on pathological examination than in clinical features. The diagnosis of cardiopulmonary bilharziasis is made by pulmonary biopsy which shows an occlusive angiitis with chronic inflammatory cells, and arteriolar medial hypertrophy. The prognosis is dependent upon development to schistosomal cor pulmonale and right ventricular failure. The newly developed drugs are effect in cardiopulmonary bilharziasis, in experimental studies. PMID- 2112431 TI - [Human bilharziasis in the Near-East Mediterranean countries. Historical aspects and current distribution]. AB - The countries surrounding the mediterranean share geographical ethnic, historical and pathological features. Bilharziasis infectious found in these countries include S. haematobium infection in North Africa, Egypt and Near East and S. mansoni infection in Egypt and Arabian peninsula. The origin of two bilharziasis is probably West and East Africa, Egypt. PMID- 2112432 TI - BIPP--how does it work? AB - The antibacterial activity of BIPP and its constituents against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was measured by growth inhibition tests. BIPP was found to have negligible antibacterial activity. In addition, no release of iodine from BIPP was detected over a 4-week period. It is proposed that much of the evident antibacterial activity of BIPP may be a reflection of the meticulous surgical debridement that accompanies its use. In addition, BIPP makes the impregnated gauze impervious to blood and body fluids ensuring little nutrition for bacteria to thrive in its interstices. PMID- 2112433 TI - A cost-benefit analysis of prenatal diagnosis by amniocentesis in Denmark. AB - A cost-benefit analysis of amniocentesis has been performed using both the excess cost- and the replacement methods and several replacement and discount rates. In Denmark, amniocentesis is offered free of charge to various groups of pregnant women at risk for genetic disorders of the foetus. Most important is age greater than or equal to 35 years. The analysis is based on incidence and survival rates for Down syndrome (trisomy 21), Patau's syndrome (trisomy 13) and Edward's syndrome (trisomy 18), and on incidence and survival rates of children with neural tube defects. If amniocentesis were offered to all pregnant women independent of age, with a supposed participation rate of 75% and if only tangible costs and benefits were included, the analysis shows a benefit:cost ratio greater than 1.0 using discount rates of 4% and 7% (both for the excess cost- and replacement method); a benefit:cost ratio less than 1.0 is found using 10%. The ratio is approximately 1.0, if pregnant women aged 15-19 and 20-24 years are excluded, using the discount rate 10%. Calculations for other participation rates have also been performed. If intangible costs and benefit are included, the results are uncertain. PMID- 2112435 TI - Coronary artery disease in the elderly. PMID- 2112434 TI - Acute mannitol and saline volume expansion in the rat: effect on transepithelial potential difference in proximal tubules. AB - 1. Transepithelial potential difference (PDte) of proximal tubules was measured in rats under control conditions (C), and mannitol-saline and saline extracellular fluid volume expansion (MVE, SVE, respectively) under conditions of normal net lumen to basal sodium transport. 2. PDte was measured in kidneys bathed with Hartmann's solution or covered with mineral oil under both volume expanded conditions together with their controls. 3. PDte was significantly lower in kidneys bathed with Hartmann's solution than those covered with oil. 4. In MVE rats, with mineral oil covering the kidneys, PDte (expressed as mean and s.e.m.) was for the control 2.20 +/- 0.05 (n = 45) mV and MVE 1.97 +/- 0.04 (n = 36) mV, lumen positive, a significant reduction of 10% (P less than 0.001). In SVE rats, with mineral oil covering the kidneys, PDte was for C = 2.42 +/- 0.05 (n = 74) mV and SVE = 1.93 +/- 0.03 (n = 67) mV, a significant reduction (P less than 0.001) of 20%. 5. According to thermodynamic considerations, neither of these changes is sufficient to explain the 50% inhibition of Na transport measured previously during MVE and SVE with autologous tubular fluid. The present results offer further evidence supporting the idea that the inhibition of Na transport during MVE and SVE is largely due to inhibition of the active Na transporting step. PMID- 2112438 TI - Pulsed Doppler technique in evaluation of pulmonary hypertension. AB - A pulsed Doppler technique combined with cross sectional echocardiography was used to examine the flow velocity pattern in the pulmonary artery (PA) in 17 patients with PA hypertension documented by cardiac catheterization and in 16 healthy subjects as control. In healthy subjects the blood flow pattern in systole showed a round shape, in PA hypertension group it was either narrow triangular or intermediate. There was a significant correlation between the corrected acceleration time and mean PA pressure, the coefficient being -0.78. An improved correlation (r = -0.82) was found between acceleration time and natural log of mean PA pressure. Using PA acceleration time of 100 ms or less as a criteria resulted in a 76.5% sensitivity and a 100% specificity for detection of PA hypertension. This technique made the noninvasive estimation of pulmonary hypertension possible. PMID- 2112436 TI - Basement membrane invasion by first trimester human trophoblast: requirement for branched complex-type Asn-linked oligosaccharides. AB - Trophoblast cells of normal first trimester human placenta share with malignant tumor cells the ability for significant cellular proliferation and invasion of basement membranes. Because tumor cell metastasis in vivo and invasion of basement membranes in vitro have recently been shown to require the expression of -GlcNAc beta 1-6 Man alpha 1-6 Man beta 1-branched complex type Asn-linked oligosaccharides in tumor cell surface glycoproteins, we decided to determine if such structures were also necessary for invasion by trophoblast cells. We report here that invasive first trimester trophoblasts express leukoagglutinin-reactive beta 1-6 branched Asn-linked oligosaccharides on their surface. Moreover, basement membrane invasion by trophoblast was significantly inhibited by pretreating the cells with swainsonine, a non-toxic inhibitor of Golgi alpha mannosidase II which blocks beta 1-6 branching of Asn-linked oligosaccharides. The first trimester trophoblast cells pretreated with swainsonine attached more avidly to the amnion basement membrane and to an extracellular matrix (ECM) preparation compared to control non-treated erophoblast cells. Swainsonine treatment did not inhibit secretion of gelatinase or plasminogen activator activities by trophoblast cells. These results suggest that expression of beta 1 6 branched oligosaccharides in trophoblast cells may be functionally important for the implantation and placentation processes by reducing cell adhesion to ECM and thereby facilitating trophoblast cell invasion. PMID- 2112437 TI - Safety and efficacy of a lipid emulsion containing medium-chain triglycerides. PMID- 2112439 TI - Assessment of intradermal test in longitudinal surveillance of bancroftian filariasis. AB - Longitudinal surveillance was carried out consecutively during 1982-1987 in two pilot villages where bancroftian filariasis was prevalent in different severity before 1982. Intradermal test (IT) with filaria polypeptide (FPT) antigen prepared from Dirofilaria immitis was made. It was shown that the level of immediate hypersensitivity reaction to the antigen in population as shown by IT appeared to be directly proportional to both the prevalence of the disease and the infection rate of mosquitoes harbouring larval filariae before mass and selective treatment with diethylcarbamazine. Time for negative conversion of IT after chemotherapy was significantly longer in previous microfilaraemic patients than that in amicrofilaraemic cases. The selected three criteria of IT used in filariasis surveillance, namely, the positive rate, frequency of strong reaction and positive conversion rate, were diminished gradually after chemotherapy year by year, so that the three criteria were demonstrated to be useful for longitudinal surveillance of lymphatic filariasis. PMID- 2112440 TI - Studies on function of Hb Jianghua [beta 120 (GH3) Lys----Ile]. AB - Hemoglobin Jianghua (Hb Jianghua) is a new fast--moving hemoglobin variant found in China, being named after the county where it was detected. Having its primary structure analysed, we report in this paper the results of studies on its function. The absorption spectrum, response to allosteric effectors and oxygen equilibrium of the chromatographically purified Hb Jianghua showed its characteristics similar to those of purified Hb A. Its alkaline Bohr effect was normal. This indicates that a substitution of isoleucine for the 120th lysine residue of the beta chain had no significant influence upon the function of Hb molecule. PMID- 2112441 TI - Penetration of Schistosoma japonicum cercaria into host skin. AB - The anterior part of Schistosoma japonicum cercaria is a specialized head organ which can slightly stretch out and retract. There are three different types of large unicellular glands in cercarial body, consisting of one head gland, 2 pairs of pre- and 3 pairs of postacetabular glands. These glands differ in position, gross feature, histochemistry and functions. Both polysaccharase and protease activities are demonstrated in the secretions from these glands. Mode of cercarial penetration is described in detail and the penetration is effected by a combination of lytic secretions and mechanical movements. The schematic representation of the process of cercarial penetration is presented. The dynamic distributions of schistosomula in skin at different time intervals after skin penetration in various mammalian hosts are shown. Some newly transformed schistosomula die while penetrating into the skin of 7 mammalian species and the mortality rate varies with the host species, and that can also be affected by the age of cercariae following emergence from the snail. Some physiological aspects between cercariae and newly transformed schistosomula are compared. In contrast to cercariae, schistosomula are saline-adapted and water-intolerant. They were modified histochemically and antigenically. PMID- 2112442 TI - Studies on gastrin in duodenal ulcer. AB - By immunocytochemical method and radioimmunoassay, the gastrin secreting cells (G cells) and gastrin concentration in antral mucosa, gastric juice and serum in 20 patients with duodenal ulcer (DU) were studied. The number of G cells and gastrin concentration in antral mucosa showed no significant difference as compared with normal control. The number of G cells in patients with DU and antral atrophy was much higher than those with antral atrophy but with DU. It indicated that G cells were increased in number in DU, and the gastrin concentration in gastric juice (271.11 +/- 255.25 pg/ml) was much higher than in sera (74.71 +/- 43.07 pg/ml). G cells were distributed in different parts of pyloric glands, showing that gastrin in gastric juice should come directly from G cells. The disturbance of feedback mechanism in regulating gastric acidity might be an important role in hypersecretion of gastric acid in DU. The increase of gastrin concentration in gastric juice might be closely related to hyperplasia of parietal cells. PMID- 2112443 TI - Ultrasonographic diagnosis of achalasia. AB - A perspective ultrasonographic study on 10 cases of achalasia showed characteristic ultrasonographic features: dilation and persistent water retention of the gastroesophageal vestibule, symmetrical parietal thickening, and delayed or intermittent opening of the cardiac orifice after drinking. We suggest that ultrasonography should play an important role in clinical management of achalasia. If the ultrasonographic features of achalasia were known, the misdiagnosis of achalasia for cardiac carcinoma could be avoided. When an infiltrating cardiac carcinoma found to be smoothly narrowing and difficult to distinguish from achalasia radiologically, an ultrasonogram may be helpful to make a correct diagnosis. PMID- 2112444 TI - An analysis of epidemic factors in cervical cancer by conditional logistic regression model. PMID- 2112445 TI - Reference values of indicators for WHO neurobehavioral core test battery. AB - The reference values of the indicators for WHO neurobehavioral core test battery (NCTB) and the factors of age and sex on the performance preliminarily were analyzed. The results showed that there was a significant interference with the performance of behavior involved in hand movement and hand operation, a slight interference with the performance of behavior in simple reaction time, digit span and Benton visual retention, and almost no interference with the performance of behavior in mood due to age. It seemed that sex had hardly any effect on the indicators for WHO NCTB. PMID- 2112446 TI - Dynamic changes of the cervical ligamental flavum in hyperextension-- hyperflexion movement and their measurements. AB - Ten fresh cadaver cervical spine specimens were frozen and bisected through the median sagittal plane. The length, thickness of the ligamental flavum (LF) and its protruding depth into the cervical canal were measured in hyperextension, hyperflexion and mid-position. The results showed that LF was elongated and became thinner in hyperflexion and shortened, thickened, and protruded into the cervical canal in hyperextension. The protruding depth into the canal was 3.5 +/- 0.35 mm at C 5-6, 3.25 +/- 0.50 mm at C 4-5 and 2.96 +/- 0.35 mm at C 6-7 respectively. Segmental stenosis was observed at the level of intervertebral space in hyperextension. PMID- 2112447 TI - Intramural pericyte degeneration in early diabetic retinopathy study in vitro. AB - An experimental model of diseased pericytes was established by using cultured bovine retinal capillary pericytes in high--glucose medium. The high glucose stimulated polyol pathway, reduced cellular myo-inositol content and disturbed inositol phospholipid metabolism which resulted in a decrease in inositol trisphosphate (IP3) level. The correlation of suppressed IP3 levels with reduced DNA synthesis was evident. These findings suggested the biochemical mechanism by which retinal pericytes degenerate in high glucose. To supplement myo--inositol and/or an aldose reductase inhibitor to the high--glucose medium largely reversed the suppressed IP3 level and the decreased DNA synthesis. Therefore, these two manipulations may be considered as in vitro therapy to treat sick pericytes induced by high glucose. PMID- 2112448 TI - Observation on anti-brain antibody in serum of 110 epileptics. AB - Cerebrocyte antigens of human embryo and indirect assay of solid phase ELISA were applied to measure concentrations of IgG subunit of serum anti-brain antibody (ABA) and other immunological indexes in 110 epileptics, 36 neurasthenic patients and 52 normal individuals. The results showed that the levels and abnormal rate of serum ABA in epileptic patients was much higher than those of controls (P less than 0.001). However there was no difference among the controls (P greater than 0.05). It suggested that epilepsy might be caused by certain factors resulting in the exposure of the sealed brain antigen which in turn stimulates ABA production and autoimmune responses. The serum level of ABA was correlated with that of serum IgG and IgA (P less than 0.05), but not with age, duration of disease, seizure types and the use or nonuse of anticonvulsive drugs (P greater than 0.05). PMID- 2112449 TI - First isolation of Legionella gormanii in China. AB - The first strain of non-Legionella pneumophila, L-88-1, was isolated from some condensed water in a steam discharge pipe extending from a boiler in China. The organism was characterized by serologic, biochemical, DNA hybridization and electron microscopic studies. It was identified to be L. gormanii. PMID- 2112450 TI - Advances in nuclear medicine in China. PMID- 2112451 TI - Respiratory and metabolic ultradian (40 min